Evolution and management of diabetic tractional papillopathy: an optical coherence tomographic study.
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Adult↗
Biomedical subjects
N Deshpande
Publications and source records attributed to N Deshpande.
Dynamics of FSH-induced follicular growth in subfertile women: relationship with age, insulin resistance, oocyte yield and anti-Mullerian hormone.
BACKGROUND: During excess FSH treatment, different categories of follicles can be discerned: those responding and appearing to grow immediately (FolsS8) and those appearing subsequently during the follicular phase (Fols/d). These follicular categories were explored in cycles of assisted reproduction in the context of follicular biology, including primordial follicle pool (PFP) depletion, age, insulin resistance and potential markers. METHODS: Follicular cohorts were examined in 365 conventional ART cycles and related to patient insulin sensitivity, plasma FSH and anti-Mullerian hormone (AMH). RESULTS: Age had no influence upon the FolsS8 category but was associated with a significant (P < 0.005) decline in the Fols/d. In contrast, insulin-resistant polycystic ovary syndrome (IR-PCOS) showed a significant (P = 0.005) increase in FolsS8. Circulating AMH correlated strongly with oocyte yield and Fols/d. CONCLUSION: Age showed little impact on the initial follicular cohort, but a significant impact upon the secondary cohort, while insulin resistance appeared to promote the former category alone. The disturbance to follicular dynamics and AMH in IR-PCOS reflected a larger stockpile of FSH-sensitive follicles. Circulating AMH appears to represent all categories of antral follicles observed.
Adult↗
Follicular diameters in conception cycles with and without multiple pregnancy after stimulated ovulation induction.
BACKGROUND: Controlled ovulation induction and intrauterine insemination (OI-IUI) is associated with multiple pregnancies, which are a cause of much concern. No reliable datasets have shown clear criteria for predicting multiple pregnancy. The aim of this study was to eliminate a number of variables by examining only conception cycles to determine ultrasound criteria posing risks of multiple pregnancy. METHODS: 112 OI-IUI conception cycles (multiple pregnancy rate 19.6%) were analysed retrospectively to identify factors that may be used to evaluate multiple pregnancy risk. Analyses of ultrasound data on the day of hCG administration allowed study of the role of primary, secondary and tertiary follicle diameters (FD). RESULTS: There were no multiple pregnancies in cases where there was a single FD > or = 14 mm, and no higher-order pregnancies where the tertiary follicle measured <14 mm. Follicles with an FD of 15 mm showed an 8% attributable implantation rate. CONCLUSIONS: Revision of the criteria for administration of the ovulatory dose of hCG should include the concept that follicles of 15 mm diameter may yield a pregnancy. We suggest that rigorous application of such criteria (critical FD of 16 mm combined with secondary FD evidence) will not reduce the programme pregnancy rate, but will reduce the incidence of multiple conceptions.
Adult↗
Prevalence of dementia in an urban Indian population.
UNLABELLED: This article reports the findings of a 3-year epidemiological survey for dementia in an urban community-resident population in Mumbai (Bombay), India, wherein the prevalence of all types of dementia was determined. METHOD: The study was conducted in three stages. Stage 1: From a potential pool of 30,000 subjects aged 40 years or more, 24,488 (male = 11,875; female = 12,613) persons completed self-report or interviewer-rated protocols based on the Sandoz Clinical Assessment Geriatric Scale, but 5,512 (18.37%) persons refused to participate. Scores on the protocol had a possible range from 0 through 34. Stage 2: Persons with a score +2 SD above the mean were selected in this stage where the persons were screened for cognitive functioning using a modified and translated version of the Mini-Mental State Examination. Individuals who scored below the 5th percentile were included in Stage 3 and underwent a detailed neurological, psychiatric, and neuropsychological evaluation as well as hematological, radiological, electrocardiographic, and electroencephalographic investigations. Diagnoses were made jointly by a neurologist, psychiatrist, and psychologist using the DSM-IV diagnostic criteria. Subjects were also rated on the Clinical Dementia Rating (CDR) scale and assessed for activities of daily living. RESULTS: One hundred five subjects with dementia (CDR > or = 0.5) were identified in this population of 24,488 persons. The prevalence rate for dementia in those aged 40 years and more was 0.43% and for persons aged 65 and above was 2.44%. Seventy-eight individuals had a CDR of > or = 1 yielding an overall prevalence rate of 0.32%, and a prevalence rate of 1.81% for those aged 65 years and older. The overall prevalence rate for Alzheimer's disease (AD) in the population was 0.25%, and 1.5% for those aged 65 years and above. AD (n = 62; 65%) was the most common cause of dementia followed byvascular dementia (n = 23; 22%). There were more women (n = 38) than men (n = 24) in the AD group. Increasing age was associated with a higher prevalence of the dementia syndrome in general as well as AD specifically. CONCLUSION: In the population surveyed, the prevalence of AD and other dementias is less than that reported from developed countries but similar to results of other studies in India. Prevalence of the dementia syndrome increased with age and was not related to gender. AD was the most common dementia and the prevalence was higher in women than in men. Results are discussed with respect to shorter life expectancy, relocation of affected persons, and differences in the risk factors as compared to developed countries.
Adult↗
Successive specification of Drosophila neuroblasts NB 6-4 and NB 7-3 depends on interaction of the segment polarity genes wingless, gooseberry and naked cuticle.
The Drosophila central nervous system derives from neural precursor cells, the neuroblasts (NBs), which are born from the neuroectoderm by the process of delamination. Each NB has a unique identity, which is revealed by the production of a characteristic cell lineage and a specific set of molecular markers it expresses. These NBs delaminate at different but reproducible time points during neurogenesis (S1-S5) and it has been shown for early delaminating NBs (S1/S2) that their identities depend on positional information conferred by segment polarity genes and dorsoventral patterning genes. We have studied mechanisms leading to the fate specification of a set of late delaminating neuroblasts, NB 6-4 and NB 7-3, both of which arise from the engrailed (en) expression domain, with NB 6-4 delaminating first. In contrast to former reports, we did not find any evidence for a direct role of hedgehog in the process of NB 7-3 specification. Instead, we present evidence to show that the interplay of the segmentation genes naked cuticle (nkd) and gooseberry (gsb), both of which are targets of wingless (wg) activity, leads to differential commitment to NB 6-4 and NB 7-3 cell fate. In the absence of either nkd or gsb, one NB fate is replaced by the other. However, the temporal sequence of delamination is maintained, suggesting that formation and specification of these two NBs are under independent control.
Animals↗
Suppression of LH during ovarian stimulation: effects differ in cycles stimulated with purified urinary FSH and recombinant FSH.
There has been much debate about the role of luteinizing hormone (LH) during follicle stimulating hormone (FSH)-treated ovarian stimulation for assisted reproduction, where the endogenous LH is suppressed using a gonadotrophin-releasing hormone analogue. The requirement for LH in oestradiol biosynthesis is established, but other effects of 'insufficiency' are less clear, and little attention has been paid to the specific origin of the FSH used. The aim of this study was to examine the roles of profoundly suppressed circulating LH concentrations in cycles of ovarian stimulation for IVF, which were affected in two large separate cohorts of patients undergoing assisted reproduction. They were stimulated by either purified urinary FSH (MHP) or recombinant human FSH (rFSH). Within each dataset, outcomes were examined with respect to the circulating concentrations of LH in the mid-follicular phase, as plasma samples were stored prospectively, and assayed retrospectively. Patients with profoundly suppressed LH showed much reduced oestradiol concentrations at mid-follicular phase and at human chorionic gonadotrophin administration in cycles treated with either MHP or rFSH. However, gross ovarian response, as became evident by FSH dose demands, duration of stimulation, and also oocyte and embryo yields and embryo cryopreservation were influenced only in cycles treated with MHP. Furthermore, no effect upon pregnancy survival was observed. Thus, it is concluded that there is a demand for additional exogenous LH treatment only in cycles treated with purified urinary FSH where the LH is profoundly suppressed.
Abortion, Spontaneous↗
Behavioural disturbances in dementia.
OBJECTS: To assess the frequency of behavioural disturbances in patients suffering from dementia and their relation to dementia severity. METHODS: The study evaluated 75 patients referred to the Memory Clinic at our hospital. Patients meeting DSM-IV criteria for dementia were included in the study. Activities of daily living (ADL) and cognitive functioning were also assessed. Patients were then rated for dementia severity using the Clinical Dementia Rating scale. Clinical data regarding behavioural disturbances was obtained from the patient (where possible) and an informant (usually the primary caregiver) who had contact with the patient at least thrice a week. RESULTS: Results showed that behavioural disturbances were present in more than 60% of the sample. Psychotic and activity associated disturbances were most common, and that these were seen more frequently in Alzheimer's disease than any other type of dementia. Further, these disturbances occurred most frequently in dementias of moderate severity but reduced as the dementia progressed further. CONCLUSION: Our results indicate that behavioural disturbances are a prominent part of dementia and that judicious use of psychiatric medication should form an important aspect of management.
Activities of Daily Living↗
Broad ligament twin pregnancy following in-vitro fertilization.
We report the first case of an ectopic twin pregnancy in the broad ligament following in-vitro fertilization and embryo transfer in a patient with a previous ipsilateral (left) salpingo-oophorectomy. The previous surgery was for endometriosis. We discuss the possible contribution of the embryo transfer technique, limitations of preventive measures and importance of transvaginal ultrasound in establishing the diagnosis.
Adult↗
Luteinizing hormone increases estradiol secretion but has no effect on progesterone concentrations in the late follicular phase of in vitro fertilization cycles in women treated with gonadotropin-releasing hormone agonist and follicle-stimulating hormone.
OBJECTIVE: To determine whether the late follicular phase increase in circulating P concentrations during controlled ovarian stimulation with GnRH-a and FSH can be influenced by addition of LH to the stimulating gonadotropin during the final 2 days. DESIGN: Randomization of patients to receive either FSH alone or FSH with LH (hMG) for the final 2 days before hCG, after follicular phase stimulation with purified FSH. SETTING: A.C.S. Unit at the Royal Infirmary, Glasgow, U.K. PATIENT(S): Patients were unselected and were undergoing IVF. INTERVENTION(S): Patients received stimulation with purified FSH (300 IU/d) until a follicle of 15 mm was observed; the regimen was then changed to either 225 IU of FSH or 225 IU of hMG. MAIN OUTCOME MEASURE(S): Estradiol and P in the peripheral circulation. RESULT(S): Significant increases in E2 concentration were observed, but there were no changes in the circulating progesterone. CONCLUSION(S): The late follicular phase increase in P is unrelated to any luteinizing process attributable to effects in the circulation or sensitization of follicular cells to LH.
Adult↗
The human transcription enhancer factor-1, TEF-1, can substitute for Drosophila scalloped during wingblade development.
The human transcription enhancer factor-1 (TEF-1) belongs to a family of evolutionarily conserved proteins that have a DNA binding TEA domain. TEF-1 shares a 98% homology with Drosophila scalloped (sd) in the DNA binding domain and a 50% similarity in the activation domain. We have expressed human TEF-1 in Drosophila under the hsp-70 promoter and find that it can substitute for Sd function. The transformants rescue the wingblade defects as well as the lethality of loss-of-function alleles. Observation of reporter activity in the imaginal wing discs of the enhancer-trap alleles suggests that TEF-1 is capable of promoting sd gene regulation. The functional capability of the TEF-1 product was assessed by comparing the extent of rescue by heat shock (hs)-TEF-1 with that of hs-sd. The finding that TEF-1 can function in vivo during wingblade development offers a potent genetic system for the analysis of its function and in the identification of the molecular partners of TEF-1.
Amino Acid Sequence↗
Novel aspects of the regulation of a cDNA (Arf1) from Chlamydomonas with high sequence identity to animal ADP-ribosylation factor 1.
ADP-ribosylation factor (ARF) is a highly conserved, low molecular mass (ca. 21 kDa) GTP-binding protein that has been implicated in vesicle trafficking and signal transduction in yeast and mammalian cells. However, little is known of ARF in plant systems. A putative ARF polypeptide was identified in subcellular fractions of the green alga Chlamydomonas reinhardtii, based on [32P]GTP binding and immunoblot assays. A cDNA clone was isolated from Chlamydomonas (Arf1), which encodes a 20.7 kDa protein with 90% identity to human ARF1. Northern blot analyses showed that levels of Arf1 mRNA are highly regulated during 12 h/12 h light/dark (LD) cycles. A biphasic pattern of expression was observed: a transient peak of Arf1 mRNA occurred at the onset of the light period, which was followed ca. 12 h later by a more prominent peak in the early to mid-dark period. When LD-synchronized cells were shifted to continuous darkness, the dark-specific peak of Arf1 mRNA persisted, indicative of a circadian rhythm. The increase in Arf1 mRNA at the beginning of the light period, however, was shown to be light-dependent, and, moreover, dependent on photosynthesis, since it was prevented by DCMU. We conclude that the biphasic pattern of Arf1 mRNA accumulation during LD cycles is due to regulation by two different factors, light (which requires photosynthesis) and the circadian clock. Thus, these studies identify a novel pattern of expression for a GTP-binding protein gene.
ADP-Ribosylation Factor 1↗
Establishment and characterization of an immortalized but non-transformed human prostate epithelial cell line: BPH-1.
This report describes the development and characterization of an epithelial cell line (BPH-1) from human prostate tissue obtained by transurethral resection. Primary epithelial cell cultures were immortalized with SV40 large T antigen. One of the isolated clones was designated BPH-1. These cells have a cobblestone appearance in monolayer culture and are non-tumorigenic in nude mice following subcutaneous injection or subrenal capsule grafting. They express the SV40 large T antigen and exhibit increased levels of p53, as determined by immunocytochemistry. Cytogenetic analysis by G-banding demonstrated an aneuploid karyotype with a modal chromosome number of 76 (range 71 to 79, n = 28) and 6 to 8 marker chromosomes. Some structurally rearranged chromosomes were observed, but the Y chromosome was normal. The expressed cytokeratin profile was consistent with a prostatic luminal epithelial cell. This profile was the same as that of primary prostatic epithelial cultures from which the BPH-1 cells were derived. In serum-free culture in plastic dishes epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, fibroblast growth factor (FGF) 1 (aFGF), and FGF 7 (KGF) induced increased proliferation in these cells whereas FGF 2 (bFGF), TGF-beta 1, and TGF-beta 2 inhibited proliferative activity. Testosterone had no direct effect on the proliferative rate of BPH-1 cells. 5 alpha-Reductase, 3 alpha-hydroxysteroid oxidoreductase, and 17 beta-hydroxy-steroid oxidoreductase activities were detected in BPH-1 cells. Expression of androgen receptors and the secretory markers, prostate specific antigen and prostatic acid phosphatase, were not detectable by immunocytochemistry, biochemical assay, or RT-PCR analysis.
Aged↗
Dietary omega 6 fatty acids and the effects of hyperthyroidism in mice.
The influence of the type of dietary fat on the effects of thyroid hormones was investigated in mice. Hyperthyroidism was achieved by providing thyroid hormones (T3 and T4) in the drinking water. Both hyperthyroid and euthyroid mice (Mus musculus) were fed isoenergetic diets containing 18% (w/w) total lipid but differing in fatty acid composition. Diets were either low in the polyunsaturated linoleic acid (18:2, omega 6) and high in saturated fatty acids (SFAs) or low in saturated fats and high in the polyunsaturated fatty acid (PUFA), linoleic acid. Treatments were maintained for 21-22 days. Plasma thyroid hormone levels, standard metabolic rate (SMR), changes in body mass, specific activities of malic enzyme (ME), Na-K-ATPase and glycerolphosphate dehydrogenase (GPDH) of the liver were measured. Fatty acid composition of the liver phospholipids was also determined. Levels of T3 (15-17 nM) and T4 (250-255 nM) were significantly higher in the respective hyperthyroid groups. There was no significant influence of the diet on hormone levels. Hyperthyroidism increased the SMR 37-44% above the euthyroid levels. A significant body weight loss of 14-18% was observed in hyperthyroid mice on the PUFA diet but not in those on the SFA diet. PUFA diet significantly reduced the activity of ME but had no effect on Na-K-ATPase or GPDH activity. Activities of Na-K-ATPase and GPDH were significantly elevated in all hyperthyroid groups. Mice on T4 and PUFA diet showed a highly significant 399% increase in GPDH activity above the euthyroid level.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
A functional model of adult human prostate epithelium. The role of androgens and stroma in architectural organisation and the maintenance of differentiated secretory function.
A functional model of adult human prostate epithelium is described. This model shows that stromal cells, but not an androgenic stimuli, are required for architectural organisation of prostate epithelium. Within an organised structure, androgenic stimulation is required for the establishment of secretory epithelial cell morphology and associated function. In the absence of stromal cells but in the presence of androgens architectural organisation and secretory function are lost. Epithelial parenchymal units (organoids) from human prostate tissue were isolated, cultured within a three-dimensional collagen matrix, and xenografted subcutaneously into athymic mouse hosts. The grafted gels were rapidly invaded by host fibroblasts. Epithelial organisation initially disappeared but was re-established concurrently with the stromal cell invasion. In intact male hosts, cuboidal and columnar cells that expressed human prostate-specific secretory markers were found. In castrated male and in female hosts epithelial structures were lined with flattened epithelium with no secretory function. This phenomenon could be reversibly replicated by treating intact male hosts with the anti-androgen Flutamide. Gels containing organoids grafted within 0.45 microns Millipore chambers were not invaded by stromal cells and rapidly lost all epithelial organisation and secretory function. When organoids cocultured with human foreskin fibroblasts were grafted within chambers, structural organisation of the epithelium was supported. These results indicate that both heterologous human fibroblasts and mouse stromal cells are capable of permissively supporting adult human prostate epithelial function.
Aged↗
Sterile-neutrino solutions to the solar puzzle.
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Journal Article↗
Tumor enzymes and prognosis in transitional cell carcinoma of the bladder: prediction of risk of progression in patients with superficial disease.
The activities of 6 enzymes of carbohydrate metabolism were estimated in superficial transitional cell carcinomas from 103 patients undergoing transurethral resection of the bladder for the first time. The patients were followed by quarterly endoscopic examinations for a maximum of 81 months (median 33 months). During followup 24 patients had progressive disease. The activities of phosphofructokinase and phosphohexose isomerase were significantly lower in tumors from patients whose disease had superficially invaded the lamina propria (stage pT1) than in others in whom it was confined to the bladder mucosa (stage pTa). Similarly the activities of the 2 enzymes were significantly higher in well differentiated (grade 1) than in moderately well differentiated (grade 2) carcinomas. Univariate analyses using the log rank test showed that neither pathological stage nor malignancy grade of the carcinoma was a significant factor in predicting the risk of progression. Of the 6 enzymes, below median activities of phosphofructokinase, lactate dehydrogenase and phosphohexose isomerase were associated with a significantly increased risk of progression in these patients. Multivariate analyses using Cox's proportional hazards model showed that the activity of lactic dehydrogenase in superficial transitional cell carcinoma is an independent prognostic factor in predicting the risk of progression. It is postulated that the measurements of the activities of the 3 enzymes in tumors from patients with superficial transitional cell carcinoma might help to select individual patients with a high risk of progression for adjuvant intravesical treatments.
Age Factors↗
Divergent effects of interferons on the growth of human benign prostatic hyperplasia cells in primary culture.
Epithelial cells from human benign prostatic hyperplasia tissues were grown in primary cultures for up to 21 days and the effects of interferons on the growth of the cells were investigated. Interferon-alpha (Wellferon) showed growth inhibition both in the presence and in the absence of 3 x 10(-10)M testosterone propionate (TP) whereas interferon-gamma stimulated growth in a dose dependent manner under similar conditions. Interferon-beta had little effect on growth at the dose levels used in the study. The growth inhibition by interferon-alpha can be induced after stimulation of growth is achieved either with TP or with interferon-gamma. Implications of these findings for clinical use of these lymphokines is discussed.
Cell Division↗
Enzyme studies in human transitional cell carcinoma of the urinary bladder.
The activities of six enzymes of carbohydrate metabolism were estimated in tissue samples from 99 patients with transitional cell carcinoma of the urinary bladder undergoing transurethral resection. The results were analysed according to the stage of the disease and the malignancy grade of the carcinoma. There were statistically significant differences in the activities of three enzymes between various stages and grades. The activities of phosphofructokinase (PFK), alpha-glycerolphosphate dehydrogenase (alpha-GPDH), and phosphohexose isomerase (PHI) showed significant decreases with increased stage and grade. Of the total of 64 patients with superficial disease at presentation, five developed progressive disease during the course of this investigation. The activities of the three enzymes in these patients were compared to the median values for the group of patients with superficial disease. The activity of PFK was observed to be below the median value in all the five patients whereas the activities of alpha-GPDH and PHI showed similar patterns in four of the five patients. These preliminary data indicate that, in association with established clinical parameters, the measurement of the activity of these three enzymes may prove useful in selecting patients with an increased potential for developing progressive disease.
Adult↗