Terminalia catappa attenuates phenylhydrazine-induced anaemia and hepato-renal toxicity in male Wistar rat by boosting blood cells, modulation of lipoproteins and up-regulation of in vivo antioxidant armouries.

AIM: This study investigated the haematinic, antihyperlipidaemic, hepato-renal protective effects of Terminalia catappa aqueous leaf extract on male Wistar rats exposed to phenylhydrazine toxicity. METHODS: Animals were exposed to phenylhydrazine (PHZ) 50 mg/kg intraperitoneal for two consecutive days thereafter, treated with T. catappa extract (100 mg/kg and 200 mg/kg) orally for 21 days. After the experimentation, animals were sedated with ketamine (70 mg/kg) and euthanized by cervical dislodgement. Blood and organs were collected for haematology and biochemical studies following standard laboratory methods. RESULTS: Our study showed that T. catappa significantly increased erythrocytes, haemoglobin, haematocrit and high density lipoprotein as well as down-regulating leukocytes, thrombocytes, ALP AST, ALT creatinine, urea, total cholesterol as well as low density lipoprotein. The liver, kidney and spleen antioxidant defence were also up-regulated against the adverse effect caused by phenylhydrazine exposure. CONCLUSION: Terminalia catappa attenuated Phenylhydrazine-induced anaemia and hepato-renal toxicity in male Wistar rat by boosting blood cells, modulation of lipoproteins and up-regulation of in vivo antioxidant armouries.

Transcranial Doppler Ultrasonography Imaging Studies in Children with Sickle Cell Anaemia in a Tertiary Hospital, Abuja, Nigeria.

BACKGROUND: Stroke risk in sickle cell anaemia (SCA) can be detected by abnormalities of cerebral blood flow velocities (CBFV), measurable by Transcranial Doppler Imaging (TCDI) ultrasonography. This has become an important strategy in the routine care of children with SCA globally. OBJECTIVES: To determine the pattern of CBFV and document the proportion of children with SCA at risk of stroke at National Hospital Abuja (NHA), Nigeria using TCDI. METHODS: This was a cross-sectional study of 130 children aged 2-16 years with SCA attending the haematology clinic at NHA. Systematic random sampling method was used in recruiting the participants and CBFV over the middle cerebral artery (MCA) were measured by TCDI technique. The criteria from the stroke prevention (STOP) trial in SCA used to stratify stroke risk, as modified for TCDI was employed to evaluate CBFV from the study. Thus, CBFV (stroke risk) were normal (standard) < 155cm/sec, conditional 155-179cm/sec and abnormal (high) >180cm/sec. RESULTS: There were 130 children with SCA, aged 7.7 ± 4.1 (mean age ± SD) years; and 59.2% were males. This study documented CBFV (stroke risk) as: normal 106 (81.5%), conditional 15 (11.5%) and abnormal (high) 9 (6.9%) in the MCA. The highest CBFV was recorded in the right MCA and ICA with 272cm/sec and 262cm/sec, respectively. There were significant interhemispheric differences between the CBFV on the right and left of PCA and ICA. CONCLUSION: This study documented that a significant proportion of children with SCA in Nigeria were at risk of stroke. Hence, the need for routine monitoring for stroke risk in children with SCA.

CONTEXTE: Le risque d'accident vasculaire cérébral dans la drépanocytose (SCA) peut être détecté par des anomalies des vitesses du flux sanguin cérébral (CBFV), mesurables par échographie transcrânienne d'imagerie Doppler (TCDI). Ceci est devenu une stratégie importante dans la prise en charge de routine des enfants atteints de SCA dans le monde. OBJECTIFS: Déterminer le modèle de CBFV et documenter la proportion d'enfants atteints de SCA à risque d'accident vasculaire cérébral à l'hôpital national d'Abuja (NHA), Nigéria en utilisant TCDI. cm / s. MÉTHODES: Il s'agissait d'une étude transversale de 130 enfants âgés de 2 à 16 ans atteints de SCA fréquentant la clinique d'hématologie de la NHA. La méthode d'échantillonnage aléatoire systématique a été utilisée pour recruter les participants et le CBFV sur l'artère cérébrale moyenne (ACM) a été mesuré par la technique TCDI. Les critères de l'essai de prévention des AVC (STOP) dans SCA utilisés pour stratifier le risque d'AVC, tels que modifiés pour le TCDI, ont été utilisés pour évaluer le CBFV de l'étude. Ainsi, les CBFV (risque d'accident vasculaire cérébral) étaient normaux (standard) <155 cm/s, conditionnels 155-179 cm / s et anormaux (élevés) e "180. RÉSULTATS: Il y avait 130 enfants avec SCA, âgés de 7,7 ± 4,1 (âge moyen ± ET) ans; et 59,2% étaient des hommes. Cette étude a documenté le CBFV (risque d'AVC) comme: normal 106 (81,5%), conditionnel 15 (11,5%) et anormal (élevé) 9 (6,9%) dans le MCA. Le CBFV le plus élevé a été enregistré dans le droit MCA et ICA avec 272 cm / sec et 262 cm / sec, respectivement. Il y avait des différences interhémisphériques significatives entre le CBFV à droite et à gauche du PCA et de l'ICA. CONCLUSION: Cette étude a documenté qu'une proportion significative d'enfants atteints de SCA au Nigéria étaient à risque d'accident vasculaire cérébral. D'où la nécessité d'une surveillance de routine du risque d'AVC chez les enfants atteints de SCA.

Serum Testosterone, 17ß-Estradiol and PSA Levels in Subjects with Prostate Disorders.

Prostate carcinoma is the most frequently diagnosed malignancy and the second leading cause of death as a result of cancer in men in the US and other parts of the world. There are conflicting reports on the serum levels of testosterone and 17ß-estradiol (E2) in benign prostatic hyperplasia (BPH) and prostate cancer. This study was designed to evaluate the serum concentrations of these hormones in patients with these disorders. Serum levels of prostate specific antigen (PSA), total testosterone and estradiol were determined in 228 subjects comprising of 116 subjects with BPH, 62 subjects with prostate cancer (CaP) and 50 age-matched apparently healthy controls, using ELISA methods. PSA levels were significantly elevated (p < 0.05) in BPH subjects than controls, while there was no significant difference (p > 0.05) in testosterone and estradiol levels of these subjects. PSA and estradiol levels were significantly higher (p < 0.05) in CaP subjects than in controls, while there was no observed significant difference (p > 0.05) in testosterone levels. CaP subjects had significantly raised PSA, testosterone, and estradiol levels than BPH subjects. The mean molar ratio of testosterone: E2 was lowest among CaP patients (134:1) and highest among controls (166:1). Significant positive correlation between PSA and 17ß-estradiol was observed in prostate disorders (BPH and CaP patients: r = 0.347; p = 0.000). Significant negative correlations between testosterone and PSA were also observed among BPH patients (r = -0.221, p = 0.049) and control subjects (r = -0.490, p = 0.000). No significant correlation existed between testosterone and PSA in CaP patients (r = 0.051, p = 0.693). Correlations between age and estradiol in both BPH and CaP were not significant (p > 0.05). This study has shown that, there was a significant increase in serum estradiol in CaP subjects, while the testosterone levels in both BPH and CaP subjects were not different from those of controls.

Enhancing ESL students' academic achievement in expository essay writing using digital graphic organisers: A mixed-methods research.

Students in Nigerian English language classrooms encounter difficulty in writing. However, the utilisation of metacognitive strategies has the potential to aid students in organising their thoughts during writing for better achievement. Therefore, this study aims to examine the effect of digital graphic organisers on secondary school students' achievement in expository essay writing and the students' perceptions of writing challenges and the impact of the strategy. The study adopted a mixed-methods research design consisting of a within-group experimental design and focus group interview. Five research questions and one hypothesis are formulated to guide the study. An intact class size of 38 students is the subject of the study, while an expository essay writing achievement test and a focus group interview were used for data collection. Percentage, mean and standard deviation, and thematic analysis were used in answering the research questions, while a paired sample t-test was used to test the null hypothesis at 0.05 significance. The study found a statistically significant difference between students' mean achievement scores before and after exposure to digital graphic organiser charts when writing expository essays.

Quality of life following successful repair of vesicovaginal fistula in Nigeria.

INTRODUCTION: The impact of obstetric vesicovaginal fistula (VVF), which continues to occur among women in developing countries, can severely affect the health of the women while the condition persists. This study was designed to discover the effect of successful VVF repair on affected women's quality of life. METHODS: A comparison of the quality of life of a cross-section of women who had VVF was carried out before and 6 months after successful repair. Quality of life was assessed using the WHO Quality of Life (WHOQOL)-BREF Questionnaire. RESULTS: Of the 150 women studied, only 20% felt satisfied with their general state of health and quality of life before the repair, while this increased to 90% following successful repair (highly statistically significant at p<0.000). In the physical health domain, the mean quality of life score was 67.9 ± 4.4 before and 69.3 ± 3.4 after successful repair (p<0.01). In the mental health domain, the mean quality of life score was 32.4 ± 8.7 before and 74.7 ± 3.2 after successful repair (p<0.005). In the social health domain, the mean score was 20.2 ± 2.7 before and 69.7 ± 2.3 after successful repair (p<0.001). In the environment domain, the mean score of quality of life was 60.3 ± 4.3 before repair and 59.7 ± 2.7 after successful repair (comparable at p<0.2). CONCLUSION: Successful repair of VVF is associated with significant improvement in the multidimensional quality of life among affected women.

Systematic review of climate change impact research in Nigeria: implication for sustainable development.

There is evidence that Nigeria is already experiencing environmental challenges attributed to climate change (CC) and its impacts. This has clearly highlighted the need for knowledge-based strategies to help plan adequate mitigation and adaptation measures for the country. One of the basic requirements to ensure such strategies is the development of a database of national CC research. This will aid in the assessment of past and present scientific publications from which directions for future study can be mapped. The present study used standard, systematic, and bibliographic literature reviews to analyse the trend, focus, spatial variability, and effectiveness of published research on CC impacts in Nigeria. Four thematic areas of CC impact research were defined: Agriculture, Environment, Human and Multi-disciplinary study. A total of 701 articles were found to be relevant and the review shows that CC impacts and adaptations in the literature vary across research categories and locations. The period between 2011 (68 studies) and 2015 (80 studies) showed a tremendous rise in CC impact research with a peak in 2014 (84 studies). Studies in the agriculture category had the highest publications in 23 States of Nigeria. The review revealed three research gaps: (1) lack of research that investigated the magnitude of present and potential future impacts in the aquatic environment (2) little attention on CC impacts and adaptation in the Northern regions of Nigeria (3) absence of study investigating the effects of multiple variables of CC at the same time. The findings suggest that it would be useful to advance CC research in Nigeria beyond perceptive approaches to more quantitative ones. This is particularly important for highly vulnerable animals, crops, locations, and for better planning of adaptation strategies.

Human prothymocytes. Membrane properties, differentiation patterns, glucocorticoid sensitivity, and ultrastructural features.

Thymic precursor cells (prothymocytes) comprise a large proportion of the fetal thymic cell population, but are less frequently encountered in the postnatal thymus, where they compose < 1% of the entire population. In the present study we attempted to characterize a number of properties of the prothymocytes obtained from human fetal thymic tissues after depletion of the E-rosette thymocyes on a Ficoll-Hypaque gradient. The prothymocytes are larger than the thymocytes and show a different nuclear chromatin pattern. This subset of cells lacks the E-rosetting and natural-attachment capacities and, unlike thymocytes, does not bind the lectin peanut agglutinin. Human prothymocytes are highly sensitive to the in vitro cytolytic effect of hydrocortisone, whereas the thymocytes are resistant. Long-term in vitro culture of prothymocytes resulted in the expression of thymocyte characteristics together with a burst of mitotic activity. Results of this study indicate that the rate of the prothymocyte proliferation is regulated by the small thymocytes present in the same suspension.

Cell adhesiveness is related to tumorigenicity in malignant lymphoid cells.

Mouse lymphoma cells (S49) that grow in suspension culture were selected for increased tumorigenicity through continuous passages in syngeneic BALB/c mice. Developing tumors were classified as high grade malignant lymphoma, small noncleaved type. Variants were selected from these tumorigenic cells that were able to grow as a monolayer attached to their substrate, resembling, in this respect, fibroblastoid cells. Whereas the tumorigenic suspension-growing parental cells were able to induce progressive tumors with an inoculum as low as 100 cells per mouse, the adherent cells were unable to develop as tumors even at an inoculum of 1 X 10(8) cells per mouse. In addition, mice inoculated once with live adherent cells were immunized against 1 X 10(7) suspension-growing cells. Involvement of an immune response in the rejection of tumorigenic S49 cells was suggested by (a) adoptive transfer experiments in which spleen cells from immunized mice protected naive mice and (b) the appearance of antibodies in the sera of immunized syngeneic mice that specifically recognized both adherent and suspension-growing S49 cells and detected differences in [35S]methionine-labeled antigens from these cells. Antibodies raised in rabbits against adherent cells recognized three proteins of 34,000, 61,000, and 72,000 apparent molecular weight in radiolabeled adherent cell extracts that are either absent or present in small amounts in extracts of suspension-growing tumorigenic S49 cells. These findings, taken together with our previous report (Hochman, J., A. Katz, E. Levy, and S. Eshel, 1981, Nature (Lond.), 290:248-249), suggest the S49 system as a novel system for studying growth control in malignant lymphoid cells.

[Diurnal fluctuations of protein contents and the pH dependence of beta2-microglobulin stability in urine].

Diurnal fluctuations of protein excretion into urine and the effect of urinary pH on the urinary protein concentrations were studied in patients with various kidney diseases. The diurnal kinetics of gamma-immunoglobulin, transferrin, albumin, alpha1-microglobulin, gamma-immunoglobulin light chains, and the retinol-binding protein proved to positively correlate with the diurnal fluctuations of proteinuria and to negatively correlate with urinary pH. Diurnal changes in urinary beta2-microglobulin content did not correlate with those of any other protein. Oral bicarbonate intake alkalinized the urine, increased the urinary beta2-microglobulin content, and led to a direct correlation between beta2-microglobulin excretion and excretion of other low-molecular proteins. Thus, proteinuria, single protein excretion, and urinary pH displayed diurnal rhythmicity in the patients; beta2-microglobulin was unstable in acid urine and its urinary level depended on the urinary pH.

The effectiveness of the anti-CD11d treatment is reduced in rat models of spinal cord injury that produce significant levels of intraspinal hemorrhage.

We have previously reported that administration of a CD11d monoclonal antibody (mAb) improves recovery in a clip-compression model of SCI. In this model the CD11d mAb reduces the infiltration of activated leukocytes into the injured spinal cord (as indicated by reduced intraspinal MPO). However not all anti-inflammatory strategies have reported beneficial results, suggesting that success of the CD11d mAb treatment may depend on the type or severity of the injury. We therefore tested the CD11d mAb treatment in a rat hemi-contusion model of cervical SCI. In contrast to its effects in the clip-compression model, the CD11d mAb treatment did not improve forelimb function nor did it significantly reduce MPO levels in the hemi-contused cord. To determine if the disparate results using the CD11d mAb were due to the biomechanical nature of the cord injury (compression SCI versus contusion SCI) or to the spinal level of the injury (12th thoracic level versus cervical) we further evaluated the CD11d mAb treatment after a T12 contusion SCI. In contrast to the T12 clip compression SCI, the CD11d mAb treatment did not improve locomotor recovery or significantly reduce MPO levels after T12 contusion SCI. Lesion analyses revealed increased levels of hemorrhage after contusion SCI compared to clip-compression SCI. SCI that is accompanied by increased intraspinal hemorrhage would be predicted to be refractory to the CD11d mAb therapy as this approach targets leukocyte diapedesis through the intact vasculature. These results suggest that the disparate results of the anti-CD11d treatment in contusion and clip-compression models of SCI are due to the different pathophysiological mechanisms that dominate these two types of spinal cord injuries.

In vivo T-lymphocyte response against spontaneous reticulum cell neoplasms in SJL/J mice.

The properties of lymphocytes associated with reticulum cell neoplasms (RCN) (type B) occurring spontaneously in SJL/J mice were examined. The activity of 20 alpha-hydroxysteroid dehydrogenase (20 alpha-SDH) was used as a marker for activated T-cells. High levels of this enzyme were found in cell suspensions of tumors taken from 6- to 7-month-old mice. Treatment of the cells derived from tumorous organs with anti-theta serum and complement resulted in a loss of the 20 alpha-SDH activity; this indicated that T-lymphocytes populate the RCN. The activated T-cells in the neoplastic tissue were larger than small lymphocytes. In the more advanced stage of tumor growth seen in 1-year-old mice, the percentage of malignant reticulum cells was low and the neoplastic tissue showed low levels of 20 alpha-SDH activity. Tumor cells irradiated in vitro triggered syngeneic lymphocytes to proliferate in tumor-lymphocyte mixed cultures. The T-cell proliferative response measured by [3H]thymidine incorporation was accompanied by a marked increase in 20 alpha-SDH activity. The spleen cells taken from mice bearing old tumors that showed marked fibrosis did not respond to T- and B-cell mitogens. Histologically, the structure of the spleen was preserved, with few or no tumor cells. Spleen cells from age-matched healthy mice responded to mitogens.

Image-guided core-needle biopsy in malignant lymphoma: experience with 100 patients that suggests the technique is reliable.

PURPOSE: In an initial evaluation of 1,500 computed tomography (CT)-guided core-needle biopsies performed at our institute during the period from 1989 to 1994, we encountered 100 patients with the diagnosis of lymphoma. Here, we review the clinical impact of 109 image-guided needle biopsies in these 100 patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). PATIENTS AND METHODS: NHL was diagnosed in 71 patients, and 29 had HD. Among the NHL patients, 17 (24%) had proven lymphoma diagnosed before the biopsy was performed; in 54 (76%) core-needle biopsy was performed as the first diagnostic procedure. Of 29 HD patients, nine (31%) were already established cases of HD, and in 20 (69%) core-needle biopsy was the first diagnostic procedure attempted. Most of the biopsies were performed under CT control using a 20- or 18-gauge Turner biopsy needle. RESULTS: Eighty-six patients received therapy based on the results of the needle biopsy alone. Fourteen patients received therapy after undergoing surgical biopsy for a suspected diagnosis of lymphoma, which could not be established with certainty on the basis of an earlier core-needle biopsy alone. In 78% of the patients, the needle biopsy saved a further surgical procedure that may have been difficult to perform because of the primary location of the tumor. CONCLUSION: From our experience in this study, image-guided core-needle biopsies provide sufficient information for the diagnosis of and subsequent therapeutic decision to treat most cases of lymphoma.

Bcl-2, Bcl-X, Bax, and Bak expression in short- and long-lived patients with diffuse large B-cell lymphomas.

Long-term cure is now possible for approximately 50% of all patients with aggressive non-Hodgkin's lymphoma (NHL). Apoptosis-related proteins play an important role in the chemosensitivity or chemoresistance of tumors. We examined the role of Bcl-2 family proteins in aggressive NHL. We retrospectively selected two groups of patients by clinical outcome: 24 patients with chemoresponsive disease and long survival (median, 88 months); and 20 patients with chemoresistant disease and short survival (median, 8 months). The expression of the apoptosis-regulating proteins, Bcl-2, Bcl-X, Bax, and Bak, in the initial biopsy samples was examined with immunohistochemical methods. Specimens containing >10% immunostained tumor cells were considered immunopositive. An inverse association was found between length of patient survival and expression of Bcl-2, Bcl-X, and Bax. Bcl-2 was expressed in 75% of short-lived patients but in only 42% of the long-lived ones (P = 0.026). Bcl-X expression was also higher in the short-lived patients (40% versus 12.5%; P = 0.036). Unexpectedly, Bax expression was strongly associated with short survival (60% versus 21%; P = 0.008). Several combinations of protein expression, i.e., Bcl-2 with Bax, Bcl-2 with Bcl-X, and Bcl-X with Bax, were different between the groups: a positive expression of these proteins was found in the short-lived patients. Furthermore, a strong association was found between the expression of Bcl-2 and Bcl-X, suggesting that Bcl-X potentiates rather than replaces the effect of Bcl-2 in NHL. In diffuse large B-cell NHL, Bcl-2, Bcl-X, and Bax expression alone or in combination is associated with chemoresistance and shortterm survival.

Accuracy of digital rectal examination to diagnose prostate cancer confirmed by needle biopsy reports: A 3­year hospital-based study

Background: Digital rectal examination (DRE) is an indispensable tool for provisional diagnosis of prostate diseases. When abnormal prostate examination findings are elicited, a diagnosis of prostate cancer (Pca) is usually entertained and further tests to confirm or rule out the presence of Pca demands histological examination of biopsied tissue. A combination of DRE findings and serum PSA increases the predictive value for Pca diagnosis. In this study, we evaluated the degree of accuracy of DRE to diagnose Pca confirmed by histology reports of biopsy specimens.Materials and Methods: Two hundred and six (206) patients were studied over a period of three years. Information retrieved from their case notes were entered into a well-structured protocol for management of prostatic diseases. Analysis of variables collated was performed with the statistical package for the social sciences (SPSS) version 20.0. Frequency table was used to analyze categorical variables while descriptive statistics was used for continuous variables. Level of significance was set at P<.05.Results: 206 patients were studied with mean age of 68.23±8.71 years ranging from 48 to 91 years. Men in the Pca group were older than those in the BPH group. Abnormal DRE was associated with high grade tumours, and high level of aggressive tumour characteristics by WHO grade group standard.Conclusion: DRE has a high level of accuracy in predicting a diagnosis of Pca which was confirmed by histology reports especially in prostates with abnormal findings

A novel method for localization of gonadotropin releasing hormone receptors.

Two 125I-labeled analogs of GnRH, [acidobenzoyl-D-Lys6]GnRH (I) and [D-Lys6]GnRH (II) were used for the localization of GnRH receptors in pituitary cells. The analogs exhibited high binding affinity to pituitary membrane preparations and after photoactivation (analog I) or cross-linking with glutaraldehyde (analog II), these analogs are bound covalently to pituitary cells. The distribution of the labeled hormones by light and electron microscopic autoradiography indicated that after exposure of pituitary cells to 125I-labeled hormones at 4 C (90 min), most of the labeled hormones were associated with the cell surface membrane, while at 37 degrees C (30 min) most of the cell-bound labeled hormones were internalized.

Localization of growth hormone-releasing hormone in the human hypothalamus and pituitary stalk.

The localization of the recently identified GH-releasing hormone (GHRH) in the human hypothalamus and pituitary stalk was determined by microdissection techniques and a specific RIA for GHRH. The highest concentrations of GHRH immunoreactivity (IR-GHRH) in the hypothalamus were found in the area of the infundibular nucleus (83 +/- 4 ng/mg protein; average +/- range). Lower quantities were found in other hypothalamic regions. Very high concentrations of IR-GHRH were present in the upper portion of the pituitary stalk (1454 +/- 48 ng/mg protein), and they decreased gradually toward the distal end of the stalk (21 +/- 3 ng/mg). This concentration gradient suggests that the peptide reaches the anterior pituitary mainly by way of the long portal vessels. Somatostatin, the second neuropeptide involved in the regulation of GH secretion from the anterior pituitary, had a pattern of distribution along the pituitary stalk very similar to that of IR-GHRH.

Does bacteriorhodopsin energize the membranes of animal mitochondria under light?

A suspension of freeze-thawed mitochondria mixed with purple membranes from Halobacteria was illuminated with visible light. It was found that the light exposure prevented inhibition of succinate oxidation. The illumination also led to a decrease in inhibition of the rate of ferricyanide reduction by rat liver mitochondria in the presence of succinate. Both phenomena are explained by the fact that oxalacetate inhibition of succinate dehydrogenase is prevented by light-induced energization of mitochondrial membranes due to the contact with purple membranes.

A second isoform of gonadotropin-releasing hormone is present in the brain of human and rodents.

Gonadotropin-releasing hormone-I (GnRH-I), present in the mammalian hypothalamus, regulates reproduction. In this study we demonstrate, for the first time, that an additional isoform of GnRH, [His5, Trp7, Tyr8] GnRH-I (GnRH-II) is present in the brain of the mouse, rat and human. Human and rat brain extracts contain two isoforms of GnRH, GnRH-I and GnRH-II, which exhibited identical chromatographic properties to the respective synthetic peptides, in high performance liquid chromatography. Using immunohistochemical techniques we have found that GnRH-II is present in neuronal cells that are localized mainly in the periaqueductal area as well as in the oculomotor and red nuclei of the midbrain. It is of interest to note that in the hypogonadal mouse, although the GnRH-I gene is deleted, GnRH-II is present. Substantial concentrations of GnRH-II are also present in the hypothalamus and stored in the human pituitary stalk or in the mouse median eminence. By using reverse transcription (RT)-PCR we have also found that while GnRH-II is not expressed in the cerebellum, it is expressed in all three structures of the brain stem: midbrain, pons and medulla oblongata.

The gonadotropin-releasing hormone family of neuropeptides in the brain of human, bovine and rat: identification of a third isoform.

The mammalian gonadotropin-releasing hormone (GnRH-I), which regulates reproduction, was the first isoform of GnRH that was identified in mammals. Recently, we and others have demonstrated the existence of a second isoform of GnRH in the brain of mammals. The presence of a third isoform of GnRH, GnRH-III, in the brain of mammals is reported herein. GnRH-III, extracted from the brain of bovine and human, was purified by high performance liquid chromatography, using two distinct elution programs. In both, GnRH-III was eluted at the same positions as synthetic salmon GnRH, as demonstrated by radioimmunoassay. The luteinizing hormone-releasing activity of purified GnRH-III, using dispersed rat pituitary cells, was found to be similar to that of synthetic salmon GnRH. The total amount of GnRH-III, determined by radioimmunoassay, in the hypothalamus and midbrain of humans and calves is similar to that of GnRH-I. Immunohistochemical studies demonstrated GnRH-III-containing neurons in the hypothalamus and midbrain of human and GnRH-III fibers in the median eminence of rats. The distribution of GnRH-III in the brain suggests that in addition to a putative function as a neurohormone at the hypothalamic-pituitary axis, GnRH-III may have other functions. Our present results suggest that multiple isoforms of GnRH are present in the brain of mammals, and further studies are required in order to elucidate their biological functions.

Adult-onset Niemann-Pick type C disease. Clinical, biochemical, and genetic study.

BACKGROUND: Niemann-Pick type C disease is an autosomal recessive neurometabolic disorder of unknown origin mapped to chromosome 18q11-12 in most of the studied families. In contrast to the sphingomyelin lipidoses, in Niemann-Pick type C disease, fibroblasts are impaired in intracellular homeostatic responses to exogenous low-density lipoprotein (LDL) cholesterol. Biochemical heterogeneity of the disorder in relation to abnormal LDL processing is associated with various clinical presentations, but adult-onset Niemann-Pick type C disease is rare and has not been comprehensively characterized. OBJECTIVE: To describe clinical, biochemical, and genetic features of adult-onset Niemann-Pick type C disease in 3 siblings. DESIGN AND SETTING: Case series in a tertiary care center. PATIENTS: The 3 siblings manifested a variable combination of vertical supranuclear ophthalmoplegia, ataxia, and splenomegaly. Brain magnetic resonance imaging showed cerebellar atrophy; brainstem auditory evoked responses were unobtainable, and bone marrow examination disclosed typical foam cells. The patients were 20, 26, and 28 years old and belonged to a sibship of 13 born of consanguineous healthy parents. METHODS: Esterification of exogenous LDL cholesterol in cultured skin fibroblasts and filipin staining for free intracellular cholesterol. Polymerase chain reaction-based DNA linkage study using AC microsatellite markers D18S40, D18S44, D18S480, and D18S66. RESULTS: Fibroblasts of the 3 patients showed a 23% to 58% block in the induced cholesterol esterification after 4 1/2 hours and a mild to moderate accumulation of free cholesterol. DNA study demonstrated linkage to the major 18q11-12 Niemann-Pick type C locus and identified unaffected carriers. CONCLUSIONS: These results confirm the diagnosis of the least biochemically affected Niemann-Pick type C phenotype in this family with adult-onset disease and support a correlation between the mild laboratory and clinical findings in this age group.