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1.
Vet J ; 265: 105552, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33129552

ABSTRACT

Amyloidosis in Siamese/Oriental cats is a lethal condition with variable age of clinical onset. There is no sex predisposition and clinical signs of disease usually become apparent by 1-7 years of age. In the terminal stages, the liver is enlarged and pale, and contains parenchymal hemorrhages. In the present study, pedigree data from 17 cats with clinical signs consistent with amyloidosis underwent genetic analysis. Necropsy and histopathological data were available for 10 of the 17 cats. Necropsy findings included pale, fragile and enlarged livers with capsular ruptures and parenchymal hemorrhages, and sanguineous effusions in the abdominal cavity. Congo red staining with birefringence confirmed systemic amyloidosis mostly involving the liver and thyroid gland. In four of the 10 cases, protein deposits were classified as amyloid A protein (AA-amyloid) by immunostaining. Pedigree data for all 17 affected cats indicated a familial trait. Animal threshold model analysis demonstrated that the heritability for amyloidosis was 0.56 ± 0.09 (standard error). Complex segregation analysis was used for statistical comparisons among models to determine environmental or sex dependent effects, and Mendelian, polygenic, or mixed Mendelian and polygenic inheritance patterns. A mixed model with a Mendelian and polygenic component provided the best fit to the data and thus was most likely. All other models of inheritance were rejected due to their insufficient ability to explain segregation of amyloidosis. In conclusion, we found evidence for a complex genetic basis for amyloidosis in Oriental shorthair cats.


Subject(s)
Amyloidosis, Familial/veterinary , Cat Diseases/genetics , Chromosome Segregation/genetics , Pedigree , Amyloidosis, Familial/genetics , Amyloidosis, Familial/pathology , Animals , Cat Diseases/metabolism , Cat Diseases/pathology , Cats , Female , Liver/chemistry , Liver/pathology , Male , Serum Amyloid A Protein/analysis , Thyroid Gland/chemistry , Thyroid Gland/pathology
2.
Water Resour Res ; 56(10): e2020WR027385, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33132450

ABSTRACT

Estimating parameters for distributed hydrological models is a challenging and long studied task. Parameter transfer functions, which define model parameters as functions of geophysical properties of a catchment, might improve the calibration procedure, increase process realism, and can enable prediction in ungauged areas. We present the function space optimization (FSO), a symbolic regression method for estimating parameter transfer functions for distributed hydrological models. FSO is based on the idea of transferring the search for mathematical expressions into a continuous vector space that can be used for optimization. This is accomplished by using a text generating neural network with a variational autoencoder architecture that can learn to compress the information of mathematical functions. To evaluate the performance of FSO, we conducted a case study using a parsimonious hydrological model and synthetic discharge data. The case study consisted of two FSO applications: single-criteria FSO, where only discharge was used for optimization, and multicriteria FSO, where additional spatiotemporal observations of model states were used for transfer function estimation. The results show that FSO is able to estimate transfer functions correctly or approximate them sufficiently. We observed a reduced fit of the parameter density functions resulting from the inferred transfer functions for less sensitive model parameters. For those it was sufficient to estimate functions resulting in parameter distributions with approximately the same mean parameter values as the real transfer functions. The results of the multicriteria FSO showed that using multiple spatiotemporal observations for optimization increased the quality of estimation considerably.

3.
Sci Rep ; 9(1): 11689, 2019 08 12.
Article in English | MEDLINE | ID: mdl-31406213

ABSTRACT

Canine distemper virus (CDV) causes a fatal demyelinating leukoencephalitis in young dogs resembling human multiple sclerosis. Astrocytes are the main cellular target of CDV and undergo reactive changes already in pre-demyelinating brain lesions. Based on their broad range of beneficial and detrimental effects in the injured brain reactive astrogliosis is in need of intensive investigation. The aim of the study was to characterize astrocyte plasticity during the course of CDV-induced demyelinating leukoencephalitis by the aid of immunohistochemistry, immunofluorescence and gene expression analysis. Immunohistochemistry revealed the presence of reactive glial fibrillary acidic protein (GFAP)+ astrocytes with increased survivin and reduced aquaporin 4, and glutamine synthetase protein levels, indicating disturbed blood brain barrier function, glutamate homeostasis and astrocyte maladaptation, respectively. Gene expression analysis revealed 81 differentially expressed astrocyte-related genes with a dominance of genes associated with neurotoxic A1-polarized astrocytes. Accordingly, acyl-coA synthetase long-chain family member 5+/GFAP+, and serglycin+/GFAP+ cells, characteristic of A1-astrocytes, were found in demyelinating lesions by immunofluorescence. In addition, gene expression revealed a dysregulation of astrocytic function including disturbed glutamate homeostasis and altered immune function. Observed findings indicate an astrocyte polarization towards a neurotoxic phenotype likely contributing to lesion initiation and progression in canine distemper leukoencephalitis.


Subject(s)
Astrocytes/virology , Demyelinating Diseases/veterinary , Distemper Virus, Canine/pathogenicity , Distemper/virology , Encephalomyelitis, Acute Disseminated/veterinary , Glial Fibrillary Acidic Protein/genetics , Animals , Aquaporin 4/genetics , Aquaporin 4/immunology , Astrocytes/immunology , Astrocytes/pathology , Blood-Brain Barrier/immunology , Blood-Brain Barrier/pathology , Blood-Brain Barrier/virology , Coenzyme A Ligases/genetics , Coenzyme A Ligases/immunology , Demyelinating Diseases/genetics , Demyelinating Diseases/pathology , Demyelinating Diseases/virology , Disease Progression , Distemper/genetics , Distemper/immunology , Distemper/pathology , Distemper Virus, Canine/immunology , Dogs , Encephalomyelitis, Acute Disseminated/genetics , Encephalomyelitis, Acute Disseminated/pathology , Encephalomyelitis, Acute Disseminated/virology , Gene Expression Regulation , Glial Fibrillary Acidic Protein/immunology , Glutamate-Ammonia Ligase/genetics , Glutamate-Ammonia Ligase/immunology , Glutamic Acid/immunology , Glutamic Acid/metabolism , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Proteoglycans/genetics , Proteoglycans/immunology , Signal Transduction , Survivin/genetics , Survivin/immunology , Vesicular Transport Proteins/genetics , Vesicular Transport Proteins/immunology
4.
Notf Rett Med ; 20(8): 641-648, 2017.
Article in German | MEDLINE | ID: mdl-32288636

ABSTRACT

Noninvasive ventilation (NIV) may be used to treat pediatric acute respiratory failure. Recent improvements in ventilator technology and availability of nasal and full face masks for infants and children have simplified the use of NIV even in the smallest children. Mainly patients with hypercapnic respiratory failure may benefit from noninvasive ventilation. There is some evidence available that supports the use of NIV in viral bronchiolitis, asthma and acute on chronic respiratory failure in patients with neuromuscular or chronic pulmonary disease. Furthermore, noninvasive ventilation is beneficial during prolonged weaning from invasive ventilation and to treat upper airway obstructions. Children suffering from hypoxic respiratory failure, such as community-acquired pneumonia and acute respiratory distress syndrome do not benefit from NIV. Due to possibly relevant side effects and the possibility of rapid deterioration in gas exchange in failure of NIV, invasive ventilation should be readily available; therefore, treatment with noninvasive ventilation for acute respiratory failure in children should be initiated on the pediatric intensive care ward.

5.
Z Geburtshilfe Neonatol ; 217(4): 144-6, 2013 Aug.
Article in German | MEDLINE | ID: mdl-23982941

ABSTRACT

We present the case of a female infant born prematurely at 34 weeks of gestation. Prenatally a midsized ventricular septal defect was diagnosed. Due to marked respiratory distress intubation was attempted but failed, since the tube could not be placed beyond the glottis. Oxygenation could be improved by nasopharyngeal bag ventilation. The clinical course as well as radiographic imaging was suggestive for a complete tracheal agenesis with broncho-oesophageal fistula which was confirmed at autopsy. Tracheal agenesis (TA) is a rare differential diagnosis of postnatal respiratory distress and the obstetrician or neonatologist will regularly be surprised by this malformation. Partial or complete absence of the trachea without associated malformations will be rarely diagnosed antenatally. In the case of the absence of an oesophageal fistula to the remaining airway a congenital high airway obstruction syndrome (CHAOS) ensues, leading to enlarged hyperechogenic lungs, dilated and fluid-filled trachea and bronchi and an absent tracheal flow during foetal breathing. Aetiology of TA is unknown, therapeutic options are limited thus making TA a usually fatal disorder.


Subject(s)
Bronchial Fistula/complications , Bronchial Fistula/diagnosis , Constriction, Pathologic/complications , Constriction, Pathologic/diagnosis , Infant, Premature, Diseases/diagnosis , Infant, Premature, Diseases/therapy , Respiratory Distress Syndrome, Newborn/etiology , Trachea/abnormalities , Bronchial Fistula/therapy , Constriction, Pathologic/therapy , Delivery Rooms , Diagnosis, Differential , Fatal Outcome , Female , Humans , Infant, Newborn , Infant, Premature , Neonatology/methods , Obstetrics/methods , Respiratory Distress Syndrome, Newborn/diagnosis , Respiratory Distress Syndrome, Newborn/therapy
6.
Hautarzt ; 64(9): 664-5, 2013 Sep.
Article in German | MEDLINE | ID: mdl-23681428

ABSTRACT

A small hyperpigmented nodule 4 mm in diameter with a smaller satellite lesion was noted on the left hip 5 weeks after spontaneous birth of an otherwise unharmed 490 g female infant at 23 + 5 weeks of gestation. The mother had been treated with antibiotics for a clinically suspected amniotic infection syndrome. Aspergillus fumigatus was identified in both repeated swabs of the lesions and culture of the resected tissue. The infant received liposomal amphotericin B (3 mg/kg/day) for 8 days. No new lesions were noted thereafter. There was no evidence for a primary immunodeficiency.


Subject(s)
Amphotericin B/therapeutic use , Aspergillosis/diagnosis , Aspergillosis/drug therapy , Aspergillus fumigatus/isolation & purification , Infant, Extremely Low Birth Weight , Leg Dermatoses/diagnosis , Leg Dermatoses/drug therapy , Antifungal Agents/therapeutic use , Aspergillosis/microbiology , Female , Humans , Infant, Newborn , Leg Dermatoses/microbiology , Treatment Outcome
7.
Arch Otolaryngol Head Neck Surg ; 127(8): 950-5, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11493204

ABSTRACT

BACKGROUND: Elective bedside pediatric tracheostomies in the intensive care unit have not been widely reported. Unlike in the adult population, this is not yet considered a safe or routine procedure in the pediatric population. We performed a preliminary study suggesting that bedside pediatric tracheostomies can be done safely and at reduced cost. DESIGN: Retrospective medical chart review. SETTING: Tertiary care referral center at a single university hospital. PATIENTS: Fifty-seven patients, ranging in age from 15 days to 8 years. Thirty operating room tracheostomies and 27 bedside tracheostomies were performed during a 6-year period. The mean age of the patients was 20.5 months, with no significant age difference between the 2 groups. The top 3 diagnoses necessitating tracheostomy were laryngotracheal disorders (18 patients [32%]), bronchopulmonary dysplasia (9 [16%]), and neurologic disorders (6 [11%]). INTERVENTIONS: Tracheostomy. MAIN OUTCOME MEASURES: The initial 48-hour postoperative period was examined to compare complication rates between groups. RESULTS: Overall, the 2 groups had similar complication rates (chi(2) = 0.12; P =.73). The operating room group had 3 complications (10%) related to bleeding, infection, and pneumothorax. The bedside group had 2 complications (7%), both involving pneumothorax. Each operating room tracheostomy incurred charges totaling $1693 vs $235 for each bedside tracheostomy. CONCLUSIONS: Historically, pediatric tracheostomy has been viewed as a technically demanding procedure with a high complication rate, thus encouraging routine operating room use. We found that pediatric tracheostomy performed in the intensive care unit, with attention to prudent patient selection and adherence to consistent, sound techniques, was as safe as operating room tracheostomy.


Subject(s)
Point-of-Care Systems , Tracheostomy , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Intensive Care Units, Pediatric , Male , Operating Rooms , Retrospective Studies , Safety , Tracheostomy/adverse effects
8.
Endocrinology ; 142(9): 3842-9, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11517161

ABSTRACT

The insulin receptor substrates are docking proteins that bind various receptor tyrosine kinases and signaling proteins. Previous studies have shown that E2 or progesterone can regulate the relative abundance of insulin receptor substrate-1 and -2 in cells and tissues. For instance, uterine insulin receptor substrate-2 was decreased markedly at 24 h after E2 treatment of mice. In the present study we used various in vivo experimental approaches to examine the mechanism by which E2 influences uterine insulin receptor substrate-2 expression. Uterine insulin receptor substrate-2 mRNA levels were diminished after E2 treatment, but this diminution did not account for the total reduction in insulin receptor substrate-2 protein, suggesting that the E2-induced decrease in insulin receptor substrate-2 is not regulated solely at the mRNA level. Cotreatment with progesterone prevented the E2-stimulated reduction in insulin receptor substrate-2 protein at 24 h after hormone exposure. In addition, MG-132 and epoxomicin, inhibitors of proteasomal protease activity, inhibited the E2-induced decrease in uterine insulin receptor substrate-2 protein levels, and this correlated to an increase in uterine protein ubiquitination. Insulin receptor substrate-2 protein was diminished in uteri of E2-treated insulin receptor substrate-1-null mutant mice, but not in E2-treated IGF-I-null mutant mice. Furthermore, E2-induced diminution of uterine insulin receptor substrate-2 protein was only partially inhibited in the presence of wortmannin, a PI3K inhibitor. Collectively, these data suggest that the E2-induced decrease in uterine insulin receptor substrate-2 requires IGF-I signaling, is not dependent solely on insulin receptor substrate-1 and PI3K, and is blocked by progesterone as well as by pharmacological inhibition of proteasomal protease activity. We speculate that the IGF-I-activated IGF-I receptor, in response to E2, directly or indirectly modifies insulin receptor substrate-2, probably through phosphorylation, leading to ubiquitination and subsequent degradation of this docking protein by the proteasome. This degradation could be a regulatory step to inhibit insulin receptor substrate-2-dependent signaling in the uterus.


Subject(s)
Cysteine Endopeptidases/physiology , Estradiol/pharmacology , Insulin-Like Growth Factor I/physiology , Multienzyme Complexes/physiology , Phosphoproteins/metabolism , Uterus/metabolism , Androstadienes/pharmacology , Animals , Estrus/physiology , Female , Humans , Insulin Receptor Substrate Proteins , Insulin-Like Growth Factor I/deficiency , Insulin-Like Growth Factor I/genetics , Intracellular Signaling Peptides and Proteins , Mice , Mice, Inbred Strains , Mice, Knockout/genetics , Ovary/physiology , Phosphodiesterase Inhibitors/pharmacology , Phosphoproteins/antagonists & inhibitors , Phosphoproteins/deficiency , Phosphoproteins/genetics , Progesterone/pharmacology , Proteasome Endopeptidase Complex , Proteins/metabolism , RNA, Messenger/metabolism , Reference Values , Ubiquitins/metabolism , Wortmannin
9.
Pacing Clin Electrophysiol ; 24(11): 1585-95, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11816626

ABSTRACT

In 19 patients paced and medicated for bradycardia tachycardia syndrome (BTS), AAIR and DDDR pacing were compared with regard to quality of life (QoL), atrial tachyarrhythmia (AFib), exercise tolerance, and left ventricular (LV)function. Patients had a PQ interval < or = 240 ms during sinus rhythm, no second or third degree AV block, no bundle branch block, or bifascicular block. In DDDR mode, AV delay was optimized using the aortic time velocity integral. After 3 months, QoL was assessed by questionnaires, patients were investigated by 24-hour Holter, cardiopulmonary exercise testing (CPX) was performed, and LV function was determined by echocardiography. QoL was similar in all dimensions, except dizziness, showing a significantly lower prevalence in AAIR mode. The incidence of AFib was 12 episodes in 2 patients with AAIR versus 22 episodes in 7 patients with DDDR pacing (P = 0.072). In AAIR mode, 164 events of second and third degree AV block were detected in 7 patients (37%) with pauses between 1 and 4 seconds. During CPX, exercise duration and work load were higher in AAIR than in DDDR mode (423+/-127 vs 402+/-102 s and 103+/-31 vs 96+/-27 Watt, P < 0.05). Oxygen consumption (VO2), was similar in both modes. During echocardiography, only deceleration of early diastolic flow velocity and early diastolic closure rate of the anterior mitral valve leaflet were higher in DDD than in AAI pacing (5.16+/-1.35 vs 3.56+/-0.95 m/s2 and 69.2+/-23 vs 54.1+/-26 mm/s, P < 0.05). As preferred pacing mode, 11 patients chose DDDR, 8 patients chose AAIR. Hence, AAIR and DDDR pacing seem to be equally effective in BTS patients. In view of a considerable rate of high degree AV block during AAIR pacing, DDDR mode should be preferred for safety reasons.


Subject(s)
Bradycardia/therapy , Cardiac Pacing, Artificial/methods , Exercise Tolerance/physiology , Sick Sinus Syndrome/therapy , Tachycardia/therapy , Ventricular Function, Left/physiology , Aged , Aged, 80 and over , Bradycardia/diagnosis , Bradycardia/etiology , Cross-Over Studies , Double-Blind Method , Echocardiography , Electrocardiography, Ambulatory , Exercise Test , Female , Humans , Male , Middle Aged , Pacemaker, Artificial , Prospective Studies , Quality of Life , Random Allocation , Recurrence , Sick Sinus Syndrome/complications , Sick Sinus Syndrome/physiopathology , Syndrome , Tachycardia/diagnosis , Tachycardia/etiology
10.
Laryngoscope ; 111(12): 2157-61, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11802016

ABSTRACT

OBJECTIVES/HYPOTHESIS: Velopharyngeal stress incompetence in professional musicians is an uncommon but potentially career-ending problem. Pharyngeal flaps, V-Y palatal pushback procedures, Teflon or collagen injection of the posterior pharyngeal wall, and speech therapy have all been used to address this problem. The ideal procedure for this subset of patients with velopharyngeal incompetence (VPI) with high-pressure, mild VPI would be one that combines low morbidity and an expedient recovery for the busy musician. We describe an approach of endoscopically assisted autologous lipoinjection of the soft palate. STUDY DESIGN: A retrospective review of our experience treating high-pressure stress VPI in two professional musicians. METHODS: Literature review and retrospective chart review. RESULTS: Two musicians underwent autologous lipoinjection of the soft palate for stress VPI. Patients resumed full play within 2 weeks of the operation with no serious complications. There has been no recurrence of the VPI after 18 and 12 months of follow-up, respectively. CONCLUSIONS: Velopharyngeal stress incompetence in musicians is an uncommon disorder. Velopharyngeal incompetence in these patients may not present as in a typical manner with hypernasality but may go undiagnosed for years mistakenly rationalized as a declining performance ability rather than a curable structural problem. The performance demands of professional musicians necessitate a timely solution to their VPI. More precise and limited contouring of palatal bulk can be achieved through the lipoinjection technique than compared with traditional palatal V-Y pushback or a standard pharyngeal flap. Lipoinjection of the palate can be performed as an outpatient procedure with only minor discomfort and an expedient recovery for the career musician.


Subject(s)
Adipose Tissue/transplantation , Music , Palate, Soft/surgery , Pulmonary Ventilation/physiology , Velopharyngeal Insufficiency/surgery , Adult , Cleft Palate/surgery , Female , Humans , Injections , Lipectomy , Palate, Soft/physiopathology , Postoperative Complications/physiopathology , Postoperative Complications/therapy , Reoperation , Velopharyngeal Insufficiency/physiopathology
11.
Laryngoscope ; 110(10 Pt 1): 1627-32, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11037815

ABSTRACT

OBJECTIVES/HYPOTHESIS: The head and neck surgeon's fascination with parotid surgery arises from the gland's spectrum of histopathological presentations, as well as the diversity of its morphological features. A mass arising in the mid-cheek region may often be overlooked as a rare accessory lobe parotid neoplasm. This report serves to revisit the topic of accessory parotid gland neoplasms to emphasize proper management, particularly the surgical aspects, so that consequences of salivary fistula, facial nerve paralysis, and recurrence are avoided. STUDY DESIGN: This is a retrospective review of our experience with four accessory parotid gland neoplasms and five other masses mimicking this lesion. METHODS: A literature review and retrospective chart review. RESULTS: Over a 6-year period, we have encountered four true accessory lobe tumors, all pleomorphic adenomas. These presented very similarly to four other more commonly encountered masses not of salivary origin and one normal but hyperplastic accessory parotid gland. All were removed through a wide parotidectomy-style approach modified by extending incisions anterosuperiorly and inferoanteriorly. The only complication was a minor salivary fistula in one patient. There were no permanent facial paralyses. CONCLUSIONS: Accessory parotid gland neoplasms are rare and may present as innocuous extraparotid mid-cheek masses. A high index of suspicion, prudent diagnostic skills (including fine-needle aspiration [FNA] biopsy followed by computed tomography [CT] imaging), and meticulous surgical approach (extended parotidectomy-style incision and limited peripheral nerve dissection when possible) are the keys to successful management of these lesions.


Subject(s)
Parotid Neoplasms/pathology , Parotid Neoplasms/surgery , Adult , Aged , Carcinoma, Squamous Cell/pathology , Cheek , Choristoma , Diagnosis, Differential , Facial Neoplasms/pathology , Facial Neoplasms/secondary , Female , Humans , Hypertrophy , Male , Masseter Muscle/pathology , Middle Aged , Parotid Gland/anatomy & histology , Parotid Gland/surgery , Postoperative Complications/prevention & control , Retrospective Studies
12.
Endocrinology ; 141(9): 3430-9, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10965916

ABSTRACT

Recent data indicate that insulin-like growth factor I (IGF-I) may have a function in mediating the mitogenic effects of 17beta-estradiol (E2) in the uterus and in regulating the growth of uterine neoplasms. This study was designed to determine whether synthetic and plant-derived chemicals that interact with estrogen receptor-alpha (ERalpha) and elicit estrogenic responses also mimic E2 by activating the uterine IGF-I signaling pathway. Ovariectomized adult female mice were treated with both environmental and clinically relevant chemicals previously reported to display estrogenic and/or antiestrogenic properties, and their uteri were evaluated for an activated IGF-I signaling pathway. Diethylstilbestrol, 4-hydroxytamoxifen, the raloxifene analog LY353381, 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), bisphenol A, and genistein were shown to mimic E2 in the uterus by increasing the level of IGF-I messenger RNA, inducing IGF-I receptor (IGF-IR) tyrosine phosphorylation, stimulating the formation of IGF-IR signaling complexes, and increasing both proliferating cell nuclear antigen expression and the number of mitotic cells in the epithelium. The dose of chemical necessary to activate IGF-I signaling varied, with the order of potency: E2 = diethylstilbestrol > LY353381 > 4-hydroxytamoxifen > genistein > HPTE > bisphenol A. Administration of the chemicals to ERalpha knockout mice did not activate IGF-IR, indicating that ERalpha is required for activation of uterine IGF-IR by these diverse chemicals. This study demonstrates that several chemicals shown previously to display estrogenic activities also mimic E2 by activating uterine IGF-I signaling.


Subject(s)
Estradiol Congeners/pharmacology , Estrogens/pharmacology , Insulin-Like Growth Factor I/physiology , Receptors, Estrogen/metabolism , Signal Transduction/physiology , Uterus/metabolism , Animals , Benzhydryl Compounds , Blotting, Northern , Estrogen Antagonists/pharmacology , Estrogen Receptor alpha , Estrogens, Non-Steroidal/pharmacology , Female , Insulin-Like Growth Factor I/metabolism , Mice , Mice, Knockout , Mitosis/drug effects , Ovariectomy , Phenols/pharmacology , Piperidines/pharmacology , Precipitin Tests , Proliferating Cell Nuclear Antigen/metabolism , RNA, Messenger/biosynthesis , Receptors, Estrogen/agonists , Receptors, Estrogen/drug effects , Ribonucleases/metabolism , Tamoxifen/analogs & derivatives , Tamoxifen/pharmacology , Thiophenes/pharmacology
13.
J Pineal Res ; 28(4): 210-8, 2000 May.
Article in English | MEDLINE | ID: mdl-10831156

ABSTRACT

The estrogen receptor (ER)-positive MCF-7 human breast cancer cell line has been used extensively for the study of estrogen-responsive human breast cancer. However, various levels of estrogen responsiveness have been described in different stocks of MCF-7 cells. Because we have previously shown that the pineal hormone, melatonin, inhibits proliferation of MCF-7 cells and can modulate ER expression and transactivation, we investigated if various stocks of MCF-7 cells exhibit a differential responsiveness to the anti-proliferative effects of melatonin and the possible mechanisms involved. The MCF-7 stocks (M, O, H) were examined for: (1) mitogenic response to estradiol; (2) steady-state ER mRNA levels; (3) expression of the mt1 melatonin membrane receptor; (4) growth inhibition by melatonin; and (5) melatonin's modulation of expression of the ER and the estrogen-regulated genes, PgR, TGFbeta and pS2. For all of these parameters, there was a stock-specific response which showed: MCF-7M > MCF-7O > MCF-7H. These results demonstrate that there are significant differences in the responsiveness of various stocks of MCF-7 breast cancer cells to the growth-inhibitory effects of melatonin which can be correlated with both the level of ER mRNA expression and the degree of estrogen-responsiveness. These findings suggest that not only may these differences have some impact on the cells' estrogen-response pathway, but also that the primary growth-inhibitory effects of melatonin are transduced through the membrane-associated G-protein coupled mt1 melatonin receptor.


Subject(s)
Breast Neoplasms/metabolism , Melatonin/pharmacology , Blotting, Northern , Breast Neoplasms/drug therapy , Estradiol/pharmacology , Female , Humans , Protein Biosynthesis , Proteins/genetics , RNA/isolation & purification , RNA, Messenger/biosynthesis , Receptors, Cell Surface/biosynthesis , Receptors, Cytoplasmic and Nuclear/biosynthesis , Receptors, Estrogen/biosynthesis , Receptors, Estrogen/genetics , Receptors, Melatonin , Receptors, Progesterone/biosynthesis , Receptors, Progesterone/genetics , Transforming Growth Factor beta/biosynthesis , Transforming Growth Factor beta/genetics , Trefoil Factor-1 , Tumor Cells, Cultured , Tumor Suppressor Proteins
14.
Urology ; 54(6): 1082-4, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10604713

ABSTRACT

OBJECTIVES: To review published reports on urethral prolapse in the pediatric population, with a focus on diagnosis and management, and to do a retrospective review of 20 cases of urethral prolapse at an urban hospital. METHODS: A retrospective chart review of 20 consecutive cases of urethral prolapse in the pediatric population at Kings County Hospital was done. A review of the published reports on urethral prolapse from 1937 to the present was included in this study. RESULTS: Twenty patients with urethral prolapse were treated at Kings County Hospital during a 10-year period. Patients were identified by perineal bleeding and diagnosed by physical examination. All patients were successfully treated by excision of the prolapsed urethral mucosa and suturing of the remaining mucosa to the vestibule. CONCLUSIONS: Urethral prolapse is an uncommon entity that occurs primarily in prepubertal black girls. Patients may be successfully treated by excision of the prolapsed mucosa and suturing of the proximal urethra to the vestibule.


Subject(s)
Urethral Diseases/diagnosis , Urethral Diseases/surgery , Child , Child, Preschool , Female , Humans , Infant , Prolapse , Retrospective Studies
16.
Environ Health Perspect ; 107 Suppl 4: 605-11, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10421770

ABSTRACT

The workshop "Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels" was held to provide a forum for discussions and recommendations of methods and data needed to improve risk assessments of endocrine disruptors. This article was produced by a working group charged with determining the basic mechanistic information that should be considered when designing models to quantitatively assess potential risks of environmental endocrine disruptors in adults. To reach this goal, we initially identified a set of potential organ system toxicities in males and females on the basis of known and/or suspected effects of endocrine disruptors on estrogen, androgen, and thyroid hormone systems. We used this integrated, systems-level approach because endocrine disruptors have the potential to exert toxicities at many levels and by many molecular mechanisms. Because a detailed analysis of all these untoward effects was beyond the scope of this workshop, we selected the specific end point of testicular function for a more detailed analysis. The goal was to identify the information required to develop a quantitative model(s) of the effects of endocrine disruptors on this system while focusing on spermatogenesis, sperm characteristics, and testicular steroidogenesis as specific markers. Testicular function was selected because it is a prototypical integrated end point that can be affected adversely by individual endocrine disruptors or chemical mixtures acting at one specific site or at multiple sites. Our specific objective was to gather the information needed to develop models in the adult organism containing functional homeostatic mechanisms, and for this reason we did not consider possible developmental toxicities. Homeostatic mechanisms have the potential to ameliorate or lessen the effects of endocrine disruptors, but these pathways are also potential target sites for the actions of these chemicals.


Subject(s)
Endocrine System/drug effects , Environmental Pollutants/adverse effects , Homeostasis/drug effects , Models, Statistical , Spermatogenesis/drug effects , Xenobiotics/adverse effects , Adult , Humans , Male , Risk Assessment , Testis/drug effects
17.
Atherosclerosis ; 144(1): 221-8, 1999 May.
Article in English | MEDLINE | ID: mdl-10381295

ABSTRACT

It was shown in a series of studies that increased lipoprotein (a) concentration is a strong and independent risk factor for coronary artery disease. The goal of this study was to determine the significance of elevated lipoprotein (a) levels for the existence and the early manifestation of coronary artery disease by systematically recording cardiovascular risk factors in diagnostic coronary angiographies in a larger group of patients, whereby particular attention was paid to sex-specific differences. In 1011 consecutive patients who underwent coronary angiography (731 men, 280 women, mean age 59 +/- 10 years), fasting blood samples were taken immediately before the angiographies to determine the levels of cholesterol, low density lipoprotein-, high density lipoprotein-cholesterol, triglycerides and lipoprotein (a). In addition, further risk factors were qualitatively recorded. The data evaluation was carried out using the SPSSx software package univariately and multivariately with stepwise discriminant analysis. In 231 patients (144 men, 87 women) either no or only discrete coronary findings appeared, while in 780 cases (587 men, 193 women) coronary artery disease with stenoses > 50% were found. Women with coronary artery disease were significantly older than men and demonstrated higher lipoprotein levels. Women as well as men with coronary artery disease differed from healthy controls by having higher levels of lipoprotein (a) and other lipoproteins, lipoprotein (a) having the smallest error probability (P < 0.0005). The early manifestation of coronary artery disease (below the 18th age percentile) in men (< 50 years) was connected with significantly higher levels of cholesterol, triglycerides and lipoprotein (a), which emphasized their atherogenic significance in the general view. The most striking finding was that in young women (< 53 years), compared to older women with coronary artery disease--corresponding to the age-determined prevalence--significantly lower concentrations of cholesterol, triglycerides and lipoprotein (a) were found. Possible explanations include later manifestation of coronary artery disease, a steeper increase of the lipids with age, particularly of lipoprotein (a), but also a different valence of the risk factors in women.


Subject(s)
Coronary Disease/diagnosis , Coronary Disease/epidemiology , Lipoprotein(a)/blood , Adult , Age Distribution , Age of Onset , Aged , Biomarkers/analysis , Coronary Angiography , Coronary Disease/blood , Female , Germany/epidemiology , Humans , Lipoprotein(a)/metabolism , Male , Middle Aged , Risk Factors , Sensitivity and Specificity , Sex Distribution
18.
Neurology ; 50(5): 1423-8, 1998 May.
Article in English | MEDLINE | ID: mdl-9595999

ABSTRACT

OBJECTIVE: The diagnosis of a patent foramen ovale (PFO) as a cause of stroke is of increasing interest especially in young (<45 years) patients. METHODS: We studied potential right-to-left shunting using transesophageal echocardiography (TEE) and bilateral transcranial Doppler sonography (TCD) of the middle cerebral artery (MCA) simultaneously in 44 patients. All patients were younger than age 45 years and suffered from an acute ischemic stroke or transient ischemic attack. Other possible etiologies were excluded. Echo contrast medium was injected in an alternating mode via antecubital or femoral veins. Tests were performed with and without the Valsalva maneuver. The criteria for a PFO were that the contrast pass from the right to the left atrium (TEE) and early detection (<10 seconds) of more than 10 micro air bubbles in at least one MCA by TCD. RESULTS: A PFO was diagnosed in 22 patients (50%). The detection rate with TEE/TCD was 11.4%/4.5% via antecubital injection, 18%/13.6% via antecubital injection plus the Valsalva maneuver, 38.6%/36% via femoral injection alone, and 50%/50% via femoral injection plus the Valsalva maneuver. The difference between femoral and antecubital injections was significant with and without the Valsalva maneuver (p < 0.01, chi2 test). There were no differences between TEE and TCD after femoral injection with the Valsalva maneuver. The brain transit time was 4.6 +/- 2.1 seconds for femoral injection and 6.3 +/- 4.1 seconds for antecubital injection. CONCLUSIONS: The sensitivity in detecting a PFO was markedly increased by femoral injection. This may be caused by different inflow patterns to the right atrium: inferior vena caval flow is directed to the right atrial septum, whereas superior vena caval flow is directed to the tricuspid valve. Thus, femoral injection may help to improve the detection of PFO and may explain the differences between TEE and TCD findings in previous studies.


Subject(s)
Echocardiography, Transesophageal , Heart Septal Defects, Atrial/diagnosis , Adolescent , Adult , Arm/blood supply , Contrast Media , Female , Femoral Vein , Humans , Injections, Intravenous , Male , Middle Aged , Prospective Studies , Sensitivity and Specificity , Ultrasonography, Doppler
19.
Am J Community Psychol ; 26(1): 97-131, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9574500

ABSTRACT

The core objectives of this study were to document the process by which a community-based organization replicated and adapted an experimentally developed intervention to its own use and to explore the effectiveness of that HIV prevention program for male prostitutes and other patrons in New York City "hustler" bars. The intervention model employed was based on previous research with gay men (Kelly, St. Lawrence, Diaz, et al., 1991; Kelly, St. Lawrence, Stevenson, et al., 1992) and inspired by diffusion of innovation theory (Rogers, 1995). The effects of the current intervention were assessed on a sample of 1,741 male prostitutes and bar patrons. Analyses indicated significant reductions in paid, unprotected sexual intercourse and oral sex following the intervention. Analyses further indicated that the data were partially consistent with the program's model, which specified that norms were the putative mediator of behavior change in the intervention. Also, the intervention's effects varied by bar and by participants' race/ethnicity. Data support the utility of the intervention model for an urban sample of men at high risk for HIV infection. The importance of exploring the mechanisms that underlie the intervention is discussed.


Subject(s)
Community Participation , HIV Infections/prevention & control , Homosexuality, Male , Sex Work , Adolescent , Adult , Aged , Analysis of Variance , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , New York City , Peer Group , Program Evaluation , Risk-Taking , Sexual Behavior , Socioeconomic Factors , Substance Abuse, Intravenous
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