Preventing or controlling periodontitis reduces the occurrence of osteonecrosis of the jaw (ONJ) in rice rats (Oryzomys palustris).

INTRODUCTION: Osteonecrosis of the jaw (ONJ) is an adverse event that requires association of both systemic risk factors, such as powerful anti-resorptives (pARs; e.g. zoledronic acid [ZOL]), and local oral risk factors (e.g. tooth extraction, periodontitis). Whereas optimal oral health prior to initiate pARs is recognized as critically important for minimizing ONJ risk, the efficacy of preventive/maintenance measures in patients who are taking pARs is understudied. Rice rats fed a standard diet (STD), rich in insoluble fiber, develop localized periodontitis. STD-rats with localized periodontitis treated with ZOL for 18-24 wk develop ONJ. Hence, we hypothesized that controlling/preventing localized periodontitis in the ZOL-treated rats, reduces ONJ occurrence. METHODS: We used two approaches to attempt reducing periodontitis prevalence: 1) periodontal cleaning (PC); and 2) replacing the STD-diet with a nutritionally-equivalent diet high in soluble fiber (SF). 75 four-week-old male rats were weight-randomized into five groups (n = 15) in a 24-week experiment. Three groups ate the STD-diet and two the high SF-diet. STD-diet groups received intravenous (IV) vehicle (VEH) q4wks (STD + VEH), 80 µg/kg ZOL q4wks IV (STD + ZOL), or ZOL plus PC q2wks (STD + ZOL + PC). The SF-diet groups received VEH (SF + VEH) or ZOL (SF + ZOL). Jaws were processed for histopathology and evaluated for ONJ prevalence and tissue-level periodontitis. RESULTS: 1) 40% of STD + VEH rats developed maxillary localized periodontitis with no ONJ; 2) 50% of STD + ZOL rats developed ONJ; 3) 7% of STD + ZOL + PC rats developed ONJ (p < 0.01 vs. STD + ZOL); and 4) one SF + ZOL rat developed localized periodontitis, and no SF + VEH or SF + ZOL rats developed ONJ (p < 0.001 vs. STD + ZOL). CONCLUSIONS: 1) Periodontal cleaning in ZOL-treated rats decreases localized periodontitis severity and reduces ONJ prevalence; and 2) feeding a SF-diet to ZOL-treated rats reduces both incidence of localized periodontitis and ONJ. Our data indicates strong oral microbial community shifts according to oral health condition and trends in the shifts associated with diet.

Entorhinal cortex lesioning promotes neurogenesis in the hippocampus of adult mice.

Hippocampal neurogenesis in adult mammals is influenced by many factors. Lesioning of the entorhinal cortex is a standard model used to study injury and repair in the hippocampus. Here we use bromodeoxyuridine (BrdU) labeling combined with immunohistochemical identification using cell type specific markers to follow the fate of neural progenitors in the hippocampus following entorhinal cortex lesioning in mice. We show that unilateral entorhinal cortex lesioning does not alter the rate of neural progenitor proliferation in the ipsilateral dentate gyrus during the first 3 days after lesioning. However it enhances cell survival at 42 days post-lesioning leading to an increased number of beta-III tubulin and calbindin-immunoreactive neurons being produced. By contrast, when BrdU was administered 21 days post-lesioning, the number of surviving cells 21 days later was similar on the lesioned and non-lesioned sides. Thus, acutely entorhinal cortex lesioning promotes neurogenesis by enhancing survival of either neural progenitors or their progeny. However, this stimulus to neurogenesis is not sustained into the recovery period.

Transgenic rescue of Krabbe disease in the twitcher mouse.

The twitcher mouse is a natural model of Krabbe disease caused by galactocerebrosidase (GALC) deficiency. Previous attempts at rescuing the twitcher mouse by bone marrow transplantion, viral transduction, or transgenesis were only partially successful. Here, we report the transgenic (tg) rescue of the twitcher mouse with a BAC clone harboring the entire GALC. The twi/twi/hGALC tg mice exhibited growth, motor function, and fertility similar to those of nonaffected animals. These animals had normal levels of GALC activity in brain and were free of the typical twitcher demyelinating pathology. Surprisingly, GALC expression in twi/twi hGALC tg kidneys was low and galactocerebroside storage was only partially cleared. Nonetheless, these mice have been maintained for over 1 year without any sign of disease. Since pathological damage associated with GALC deficiency is confined to the nervous system, our work represents the first successful rescue of the twitcher mouse and opens the possibility of developing novel therapeutic approaches.

Interleucina-4: una citocina multifuncional / Interleukin-4: a multifunctional cytokine

Interleucina 4 (IL-4) es una citocina que regula múltiples funciones biológicas. IL-4 puede regular la proliferación, diferenciación y apoptosis en diversos tipos celulares de origen hematopoyético y no hematopoyético. Su papel en la diferenciación de los linfocitos Th0 es crítico durante la respuesta inmunitaria normal. Las respuestas frente a infecciones parasitarias también están reguladas por linfocitos Th2 inducidos por la IL-4. Por el contrario, la IL-4 y su maquinara intracelular han sido implicadas en el desarrollo de enfermedades inmunitarias incluida alergia, autoinmunidad y cáncer. Numerosas evidencias indican que la IL-4 y las células Th2 podrían promover el asma alérgica mientras que tendrían un efecto protector en artritis reumatoide. La respuesta celular a la IL-4 está mediada por un receptor que se expresa en la mayoría de los tipos celulares. Este receptor tipo I está formado por la cadena IL-4Ralfa y la cadena común gamma (gammac). La cadena gamma puede ser sustituida por la cadena IL-13Ralfa1 formando el receptor tipo II que es también receptor para la IL-13, citocina que comparte muchas funciones con la IL-4. La unión de la IL-4 a su receptor induce la activación de las tirosín cinasas JAK que median la fosforilación de proteínas intracelulares. Entre éstas, destaca el factor de transcripción STAT6. La importancia de STAT6 está demostrada por el hecho que ratones que carecen de este factor de transcripción tienen un fenotipo similar a los que carecen del receptor de la IL-4. Además, el papel de la IL-4 en enfermedades está mediado a través de la activación de STAT6. Dada la importancia de estas proteínas en enfermedades alérgicas, autoinmunitarias y cáncer, los mecanismos moleculares implicados en la activación de STAT6 podrían servir como dianas para el desarrollo de futuros tratamientos para estas enfermedades (AU)

Ergonomics in the rubber and plastics industries.

This article reviews risk factors for work-related musculoskeletal disorders in the rubber and plastics industries, as well as cost-effective methods of abatement. Return-to-work caveats also are discussed. Of interest to healthcare providers and other members of ergonomics teams, Dr. Perez presents the tools needed to implement effective ergonomics programs.

Expression of mRNA for the elav-like neural-specific RNA binding protein, HuD, during nervous system development.

The expression of mRNA for the neuronal antigen HuD (Elavl4) associated with paraneoplastic encephalomyelitis and sensory neuronopathy was evaluated in the developing and adult rat nervous system. Using RNase protection assay and non-radioactive in situ hybridization histochemistry HuD expression was shown to be expressed at high levels at the earliest time point observed (E15), but declined significantly during the first postnatal week to levels which were maintained into adulthood. In the adult, HuD expression became restricted primarily to large pyramidal-like neurons. Exceptions of note were many smaller neurons within a variety of thalamic nuclei. Expression of HuD was observed to be coincident with terminal differentiation of all neuronal structures evaluated regardless of the timing of their development, providing correlative evidence for a role in neuronal differentiation or the maintenance of neuronal phenotype. The marked restriction of HuD mRNA expression with maturity suggests that its functional role in adult neurons varies significantly throughout the CNS.

Jejunal stromal tumor with skeinoid fibers or myenteric plexoma: a case report.

Small intestinal stromal tumors with 'skeinoid fibers' are uncommon stromal tumors with an associated controversial histogenesis. Although their microscopic appearance is suggestive of a smooth muscle nature, they lack specific smooth muscle features, as evident by electron microscopy and immunohistochemistry. They also appear to lack features of neurogenic origin because they fall to react with neural/neuroendocrine markers such as S-100 protein, neuron-specific enolase and chromogranin. It is interesting, nonetheless, to note that the ultrastructural examination of these tumors may show structures reminiscent of neural differentiation, such as cytoplasmic projections, containing occasional membrane-bound, dense-core, neurosecretory-type granules, which mimick the long cytoplasmic processes seen in tumors of neural origin. Moreover, the association of these tumors with Von Recklinghausen's neurofibromatosis, as well as the presence of 'skeinoid fibers' in proven neurogenic spindle cell neoplasms such as gastrointestinal autonomic nerve tumors and schwannomas, suggests that these tumors might also be neurogenic in origin and enhances the diagnostic value of 'skeinoid fibers' as a possible ultrastructural marker of neural differentiation. Thus, light microscopic evaluation is clearly insufficient to accurately diagnose these tumors and to determine their histogenesis, electron microscopic and immunohistochemical studies being necessary. In this article the histogenesis of small intestinal stromal tumors with 'skeinoid fibers', regarding a jejunal neoplasm in a 63-year-old patient, is reviewed. The light microscopic, immunohistochemical and ultrastructural features are described and compared with findings usually seen in all those stromal tumors which may raise a differential diagnosis, such as smooth muscle stromal tumors, gastrointestinal autonomic nerve tumors, schwannomas, paragangliomas and fibrosarcomas.

Prognostic value of high serum levels of CA-125 in malignant secretory peritoneal mesotheliomas affecting young women. A case report with differential diagnosis and review of the literature.

AIMS: Very few cases of diffuse, malignant, peritoneal mesothelioma have been reported in young women. Distinction between peritoneal mesothelioma and serous epithelial tumours, including papillary serous carcinomas and borderline serous tumours, can be difficult. Differential diagnosis based on clinical appearance and imaging techniques is broad and inconclusive, thus the diagnosis must be confirmed by histological examination. Because the vast majority of tumours involving the peritoneal and serosal surfaces are due to primary or metastatic serous epithelial tumours, there is a tendency on part of pathologists to disregard the possibility of mesothelioma when examining a biopsy or excision specimen. This is especially likely to occur when mesothelioma is associated with highly elevated serum levels of CA-125, which is the typical tumoral marker of epithelial serous tumours from the ovary. The association between peritoneal mesothelioma and high serum levels of CA-125 has been reported in the literature only in two cases. CASE DETAILS: In order to avoid a misdiagnosis of this neoplasm we describe a new case of peritoneal mesothelioma in an 18-year-old woman with high serum levels of CA-125. CONCLUSIONS: Besides its clinicopathological characteristics and its histological, immunohistochemical and ultrastructural features, we describe its biological behaviour, which seems to be worst when CA-125 levels are high.

Pulmonary hemorrhage and antiglomerular basement membrane antibody-mediated glomerulonephritis after exposure to smoked cocaine (crack): a case report and review of the literature.

A case of Goodpasture's syndrome with a negative immunofluorescence examination of the lung biopsy in a 32-year-old man is described. The patient was a 40 cigarettes per day smoker, who had been smoking cocaine (crack) up to 3 weeks before hospital admission. He developed a diffuse alveolar hemorrhage with extremely acute respiratory distress, followed by renal failure with anuria. Transjugular renal biopsy, immunofluorescence and serum antiglomerular basement membrane antibody titer studies confirmed the diagnosis of Goodpasture's syndrome without linear immunoglobulin G deposits as determined by immunofluorescence examination of the alveolar basement membranes. The case illustrates the potentially complex interrelations between an autoimmune disease and exposure to substances with possible antigenic properties, besides the imperative necessity for an early, accurate diagnosis and treatment for the potential for threatening life. Moreover, the association of Goodpasture's syndrome with crack has not been previously reported.

[Extraluminal migration of a foreign body. A case report]. / Migración extraluminal de un cuerpo extraño. A propósito de un caso.

A case of extraluminal migration of a foreign body that produced chronic sialoadenitis is reported. Seven years earlier, the patient had swallowed a fish bone that was not recovered. The little literature available on these uncommon lesions is reviewed.

Structure-function analysis of TAF130: identification and characterization of a high-affinity TATA-binding protein interaction domain in the N terminus of yeast TAF(II)130.

We report structure-function analyses of TAF130, the single-copy essential yeast gene encoding the 130,000-Mr yeast TATA-binding protein (TBP)-associated factor TAF(II)130 (yTAF(II)130). A systematic family of TAF130 mutants was generated, and these mutant TAF130 alleles were introduced into yeast in both single and multiple copies to test for their ability to complement a taf130delta null allele and support cell growth. All mutant proteins were stably expressed in vivo. The complementation tests indicated that a large portion (amino acids 208 to 303 as well as amino acids 367 to 1037) of yTAF(II)130 is required to support cell growth. Direct protein blotting and coimmunoprecipitation analyses showed that two N-terminal deletions which remove portions of yTAF(II)130 amino acids 2 to 115 dramatically decrease the ability of these mutant yTAF(II)130 proteins to bind TBP. Cells bearing either of these two TAF130 mutant alleles also exhibit a slow-growth phenotype. Consistent with these observations, overexpression of TBP can correct this growth deficiency as well as increase the amount of TBP interacting with yTAF(II)130 in vivo. Our results provide the first combined genetic and biochemical evidence that yTAF(II)130 binds to yeast TBP in vivo through yTAF(II)130 N-terminal sequences and that this binding is physiologically significant. By using fluorescence anisotropy spectroscopic binding measurements, the affinity of the interaction of TBP for the N-terminal TBP-binding domain of yTAF(II)130 was measured, and the Kd was found to be about 1 nM. Moreover, we found that the N-terminal domain of yTAF(II)130 actively dissociated TBP from TATA box-containing DNA.

Proliferation and hypoxia in human squamous cell carcinoma of the cervix: first report of combined immunohistochemical assays.

PURPOSE: To characterize the distribution of hypoxia and proliferation in human squamous cell carcinoma of the cervix via an immunohistochemical approach prior to initiation of therapy. METHODS AND MATERIALS: Patients with primary squamous cell carcinoma of the cervix uteri received a single infusion of the 2-nitroimidazole, pimonidazole (0.5 g/m2 i.v.), and 24 h later punch biopsies of the primary tumor were taken. Tissue was formalin fixed, paraffin embedded, and sectioned for immunohistochemistry. Hypoxia was detected by monoclonal antibody binding to adducts of reductively activated pimonidazole in malignant cells. Staining for endogenous MIB-1 and PCNA was detected in tumor cells via commercially available monoclonal antibodies. Point counting was used to quantitate the fraction of tumor cells immunostained for MIB-1, PCNA, and hypoxia marker binding. RESULTS: Immunostaining for pimonidazole binding was distant from blood vessels. There was no staining in necrotic regions, and only minimal nonspecific staining, mostly in keratin. In general, cells immunostaining for MIB-1 and PCNA did not immunostain for pimonidazole binding. Cells immunostaining for MIB-1 and PCNA showed no obvious geographic predilection such as proximity to vasculature. Quantitative comparison showed an inverse relationship between hypoxia marker binding and proliferation. CONCLUSIONS: Immunohistochemical staining for pimonidazole binding is consistent with the presence of hypoxic cells in human tumors and may be useful for estimating tumor hypoxia prior to radiation therapy. Immunostaining for pimonidazole binding is an ideal complement to immunohistochemical assays for endogenous proliferation markers allowing for comparisons of tumor hypoxia with other physiological parameters. These parameters might be used to select patients for radiation protocols specifically designed to offset the negative impact of hypoxia and/or proliferation on therapy. The inverse relationship between pimonidazole binding and proliferation markers is a preliminary result requiring verification.

[Sebaceous carcinoma of salivary gland. Report of two cases of infrequent location]. / Carcinoma sebáceo de glándula salivar. A propósito de dos casos de localización infrecuente.

Sebaceous carcinoma is an infrequent tumor of tardy increase, locally aggressive, potentially recurrent, with natural propensity for metastasize, both loco-regional or remote (lymphogenous or hematogenus metastases). Principal sitting are the annexed glands to ocular sense (Zeis glands and specially Meibomian's). Its origin in salivary glands is exceedingly uncommon, only those arising in the parotid have been reported. Our contribution are 2 cases which source were the sublingual gland and a minor palatine salivary gland, respectively. The perusal of the literature has been negative: no one previous case of sebaceous carcinoma could be discovered in the literature.

Immobilization of nicotinic acetylcholine receptors in mouse C2 myotubes by agrin-induced protein tyrosine phosphorylation.

Agrin induces the formation of highly localized specializations on myotubes at which nicotinic acetylcholine receptors (AChRs) and many other components of the postsynaptic apparatus at the vertebrate skeletal neuromuscular junction accumulate. Agrin also induces AChR tyrosine phosphorylation. Treatments that inhibit tyrosine phosphorylation prevent AChR aggregation. To examine further the relationship between tyrosine phosphorylation and receptor aggregation, we have used the technique of fluorescence recovery after photobleaching to assess the lateral mobility of AChRs and other surface proteins in mouse C2 myotubes treated with agrin or with pervanadate, a protein tyrosine phosphatase inhibitor. Agrin induced the formation of patches in C2 myotubes that stained intensely with anti-phosphotyrosine antibodies and within which AChRs were relatively immobile. Pervanadate, on the other hand, increased protein tyrosine phosphorylation throughout the myotube and caused a reduction in the mobility of diffusely distributed AChRs, without affecting the mobility of other membrane proteins. Pervanadate, like agrin, caused an increase in AChR tyrosine phosphorylation and a decrease in the rate at which AChRs could be extracted from intact myotubes by mild detergent treatment, suggesting that immobilized receptors were phosphorylated and therefore less extractable. Indeed, phosphorylated receptors were extracted from agrin-treated myotubes more slowly than nonphosphorylated receptors. AChR aggregates at developing neuromuscular junctions in embryonic rat muscles also labeled with anti-phosphotyrosine antibodies, suggesting that tyrosine phosphorylation could mediate AChR aggregation in vivo as well. Thus, agrin appears to induce AChR aggregation by creating circumscribed domains of increased protein tyrosine phosphorylation within which receptors become phosphorylated and immobilized.

Reversible inactivation of the medial septum differentially affects two forms of learning in rats.

The contribution of the medial septum to different aspects of spatial information processing was assessed by examining the effects of reversible septal inactivation on radial maze performance of rats. In addition, the selectivity with which the medial septum affects learning was studied by testing the effects of septal inactivation on the acquisition of non-spatial information. Rats were first trained according to a spatial working memory procedure that included a 30-min delay between the first 4 (forced) choices and subsequent test (free) choices. The forced choices comprised the sample phase of the experiment while the free choices comprised the test phase. Saline or tetracaine (a local anesthetic) was injected into the medial septal area either before the sample phase, after the sample phase (i.e. at the beginning of the delay period), or just before the test phase. In contrast to the saline injections, tetracaine injected just before the sample or test phases produced a significant increase in errors at test. Tetracaine injection at the beginning of the delay period did not affect test choice accuracy. EEG records showed that septal inactivation drastically, yet temporarily, reduced the hippocampal theta rhythm. Thus, when septal inactivation occurred either before the sample phase or at the beginning of the delay period, hippocampal theta recovered by the time of the test phase. Septal inactivation also produced a significant retardation of learning on a non-spatial reference memory task, although clear improvement over trials did occur. Moreover, the results of subsequent saline injections suggest that at least some of the performance deficit was due to variables other than learning per se.(ABSTRACT TRUNCATED AT 250 WORDS)

Sudden onset of blindness in patients treated with oral CCNU and low-dose cranial irradiation.

Three patients developed the sudden onset of total blindness several months after treatment with oral CCNU and low-dose whole-brain radiation. The anterior visual system was included in the radiation field in all patients. Radiotherapy was given for a frontal-lobe glioblastoma multiforme, for central nervous system prophylaxis in a patient with oat cell carcinoma of the lung, and for a parietal-lobe glioblastoma multiforme. None of the neoplasms involved the anterior visual system. The radiation dose ranged from 3000 to 4650 rad and the oral CCNU dosage from 300 mg to 1050 mg. Patients 1 and 2 also received other chemotherapeutic agents. Patient 3 who was treated only with oral CCNU and cranial irradiation died. At autopsy the brain showed a widely infiltrating residual high-grade glioma as well as patchy coagulative necrosis with swollen axons and dystrophic calcifications. The optic chiasm showed severe demyelination, axonal loss, and hyalinized vessels. Synergism between oral CCNU and radiation may account for the blindness produced.

Acute syphilitic blindness in AIDS.

To our knowledge, bilateral syphilitic optic neuritis has not been reported in conjunction with AIDS. We document a case of a bisexual man with AIDS whose vision deteriorated overnight from 20/20 in both eyes to total bilateral blindness as a result of syphilitic retrobulbar neuritis. The implications and management of leutic disease in immunocompromised individuals are discussed.

Cell body counts in human ciliary ganglia.

Baseline cell body counts were performed on 32 human ciliary ganglia obtained during 16 consecutive autopsies. The mean age of the individuals was 53.4 yr, with a range of 17-97 yr. The cell body counts ranged from 1088-6835 cell bodies per ganglion. The mean cell body count was 2473 for specimens from the right side, 2316 for the specimens from the left side, and 2394 for the combined sides. The mean counts in men were 2837 for the right sides, 2533 for the left sides, and 2685 for both sides. The mean counts in women were 2004 for the right sides, 2036 for the left sides, and 2020 for the combined sides. The decreased number of cell bodies in women compared to the population mean was not statistically significant. There was no correlation between age and cell body counts. There was also no statistically significant difference of the cell body counts from individuals with systemic hypertension, myocardial infarction, or cancer and the population mean.

Arachnoidal cap cell hyperplasia of the intracanalicular optic nerve sheath.

Fifty-two intracanalicular optic nerves from 26 consecutive cadavers at the Dade County Medical Examiner's Office were examined for arachnoidal cap cells three cells thick or greater. Twenty specimens (77%) fulfilled these criteria with predominant involvement of the inferior and lateral aspects of the optic nerve sheath. Twenty-four specimens (92%) had psammoma bodies, and 17 specimens (65%) demonstrated corpora amylacea. Psammoma bodies as well as corpora amylacea were found with increasing frequency with age. However, our study did not show that age was an absolute factor toward the development of arachnoidal cap cell hyperplasia. The factors that incite foci of arachnoidal cap cell hyperplasia to greater activity leading in occasional individuals to the development of a meningioma remain to be determined.