Search PubMed⌕ Search

Biomedical subjects

N Shah

Publications and source records attributed to N Shah.

At least 127 records · Page 7Linked to original sources
PubMed1999

Effects of gender on exercise-induced growth hormone release.

We examined gender differences in growth hormone (GH) secretion during rest and exercise. Eighteen subjects (9 women and 9 men) were tested on two occasions each [resting condition (R) and exercise condition (Ex)]. Blood was sampled at 10-min intervals from 0600 to 1200 and was assayed for GH by chemiluminescence. At R, women had a 3.69-fold greater mean calculated mass of GH secreted per burst compared with men (5.4 +/- 1.0 vs. 1.7 +/- 0.4 microg/l, respectively) and higher basal (interpulse) GH secretion rates, which resulted in greater GH production rates and serum GH area under the curve (AUC; 1,107 +/- 194 vs. 595 +/- 146 microg x l(-1) x min, women vs. men; P = 0.04). Compared with R, Ex resulted in greater mean mass of GH secreted per burst, greater mean GH secretory burst amplitude, and greater GH AUC (1,196 +/- 211 vs. 506 +/- 90 microg x l(-1) x min, Ex vs. R, respectively; P < 0.001). During Ex, women attained maximal serum GH concentrations significantly earlier than men (24 vs. 32 min after initiation of Ex, respectively; P = 0.004). Despite this temporal disparity, both genders had similar maximal serum GH concentrations. The change in AUC (adjusted for unequal baselines) was similar for men and women (593 +/- 201 vs. 811 +/- 268 microg x l(-1) x min), but there were significant gender-by-condition interactive effects on GH secretory burst mass, pulsatile GH production rate, and maximal serum GH concentration. We conclude that, although women exhibit greater absolute GH secretion rates than men both at rest and during exercise, exercise evokes a similar incremental GH response in men and women. Thus the magnitude of the incremental secretory GH response is not gender dependent.

Adult↗
PubMed1999

Tripartite neuroendocrine activation of the human growth hormone (GH) axis in women by continuous 24-hour GH-releasing peptide infusion: pulsatile, entropic, and nyctohemeral mechanisms.

Despite the discovery of potent GH-releasing peptides (GHRPs) more than 15 yr ago and the recent cloning of human, rat, and pig GHRP receptors in the hypothalamus and pituitary gland, the neuroregulatory mechanisms of action of GHRP agonists on the human hypothalamo-somatotroph unit are not well delineated. To gain such clinical insights, we evaluated the ultradian (pulsatile), entropic (pattern orderliness), and nyctohemeral GH secretory responses during continuous 24-h i.v. infusion of saline vs. the most potent clinically available hexapeptide, GHRP-2 (1 microg/kg x h) in estrogen-unreplaced (mean serum estradiol, 12 +/- 2.4 pg/mL) postmenopausal women (n = 7) in a paired, randomized design. Blood was sampled every 10 min for 24 h during infusions and was assayed by ultrasensitive GH chemiluminescence assay. Pulsatile GH secretion was quantitated by deconvolution analysis, orderliness of GH release patterns by the approximate entropy statistic, and 24-h GH rhythmicity by cosinor analysis. Statistical analysis revealed that GHRP-2 elicited a 7.7-fold increase in (24-h) mean serum (+/-SEM) GH concentrations, viz. from 0.32 +/- 0.042 (saline) to 2.4 +/- 0.34 microg/L (GHRP-2; P = 0.0006). This occurred via markedly stimulated pulsatile GH release, namely a 7.1-fold augmentation of GH secretory burst mass: 0.87 +/- 0.18 (control) vs. 6.3 +/- 1.3 microg/L (GHRP-2; P = 0.0038). Enhanced GH pulse mass reflected a commensurate 10-fold (P = 0.023) rise in GH secretory burst amplitude [maximal GH secretory rate (micrograms per L/min) attained within a secretory pulse] with no prolongation in event duration. GH burst frequency, interpulse interval, and calculated GH half-life were all invariant of GHRP-2 treatment. Concurrently, as detected in the ultrasensitive GH assay, GHRP-2 augmented deconvolution-estimated interpulse (basal) GH secretion by 4.5-fold (P = 0.025). The approximate entropy of 24-h serum GH concentration profiles rose significantly during GHRP-2 infusion; i.e. from 0.592 +/- 0.073 (saline) to 0.824 +/- 0.074 (GHRP-2; P = 0.0011), signifying more irregular or disorderly GH release patterns during secretagogue stimulation. Cosinor analysis of 24-h GH rhythms disclosed a significantly earlier (daytime) acrophase at 2138 h (+/- 140 min) during GHRP-2 stimulation vs. 0457 h (+/-42 min) during saline infusion (P = 0.013). Concomitantly, the cosinor amplitude rose 6-fold (P = 0.018), and the mesor (cosine mean) rose 5-fold (P = 0.003). Fasting (0800 h) plasma insulin-like growth factor (IGF-I) concentrations rose by -11 +/- 12 microg/L during saline infusion and by 102 +/- 18 microg/L during GHRP-2 infusion (P = 0.0036). GHRP-2 infusion did not modify (24-h pooled) serum LH, FSH, or TSH concentrations and minimally increased serum (pooled) daily PRL (6.8 +/- 0.83 vs. 12 +/- 1.2 microg/L; P < 0.05) and cortisol (5.3 +/- 0.59 to 7.0 +/- 0.74; P < 0.05) concentrations. In summary, 24-h constant iv GHRP-2 infusion in the gonadoprival female neurophysiologically activates the GH-IGF-I axis by potentiating GH secretory burst mass and amplitude by 7- to 10-fold and augmenting the basal (nonpulsatile) GH secretion by 4.5-fold. GHRP-2 action is highly selective, as it does not alter GH secretory burst frequency, interpulse interval, event duration, or GH half-life. GHRP-2 effectively elevates IGF-I concentrations, unleashes greater disorderliness of GH release patterns, and heightens the 24-h rhythmicity of GH secretion. These tripartite features of GHRP-2's action in estrogen-withdrawn (postmenopausal) women also characterize normal human puberty and/or sex steroid regulation of the GH-IGF-I axis. However, how or whether GHRP-2 interacts further with sex hormone modulation of GH neurosecretory control in older women and men is not yet known.

Aged↗
PubMed1999

Time mode of growth hormone (GH) entry into the bloodstream and steady-state plasma GH concentrations, rather than sex, estradiol, or menstrual cycle stage, primarily determine the GH elimination rate in healthy young women and men.

We have investigated whether a reduced MCR of GH in women will account for their higher serum GH concentrations premenopausally compared with those in men. To this end, we directly compared the half-life (t 1/2) of GH and its volume of distribution (Vo) in 13 young men and 6 comparably aged women, each evaluated at three stages of the normal menstrual cycle (viz. the early follicular, late follicular, and midluteal phases). To estimate nonequilibrium GH kinetics, each subject received octreotide pretreatment to suppress endogenous GH release and then 3 randomly ordered iv bolus doses of recombinant human GH (1, 2, and 4 microg/kg). The resultant peak serum GH concentrations were 18 +/- 4, 36+/-8, and 70+/-9 microg/L in six women and 17+/-2, 30+/-4, and 84+/-25 microg/L in six men (P = NS, gender contrast). Corresponding Vo values were 66+/-1, 71+/-1, and 60+/-1 mL/kg in women and 69+/-1, 78+/-1, and 73+/-1 mL/kg in men (P = NS). Matching monoexponential GH t1/2 values were 7.6+/-0.3, 8.2+/-0.4, and 8.8+/-0.7 min in women and 9.8+/-0.8, 10+/-1, and 9.5+/-1 min in men (average 1.7 min longer in men). Regression analysis disclosed no relationship between serum estradiol concentrations and peak serum GH levels, GH t 1/2, or Vo. GH t 1/2 values were also invariant of menstrual cycle stage, e.g. t 1/2 values of 8.1+/-0.5, 9.1+/-1.0, and 8.1+/-0.4 min for the early follicular, late follicular, and midluteal phases, respectively. Corresponding normalized MCRs were 319+/-39 (early follicular), 340+/-48 (late follicular), and 340+/-71 (midluteal) L/m2 x day in women and 336+/-50 L/m2 x day in men (P = NS). In parallel equilibrium infusion studies in men, we administered GH by constant iv infusions for 240 min during octreotide suppression. At doses of 0.5, 1.5, and 4.5 microg/kg x min, steady state GH t 1/2 values were 9+/-1, 12+/-1, and 15+/-1 min (at respective steady state serum GH concentrations of 0.5+/-0.05, 2.1+/-0.2, and 7.5+/-0.5 microg/L). In a third analysis in the same volunteers, stopping the constant iv infusions revealed t 1/2 values of GH decay from equilibrium of 26+/-5 and 23+/-2.3 min for the two higher GH infusion rates. In a fourth paradigm, endogenous GH t 1/2 values, as assessed in the same individuals by deconvolution analysis of overnight (10-min sampled) serum GH concentration profiles, averaged 18+/-1.3 min. This value was intermediate between that of poststeady state decay and iv bolus elimination of GH. In summary, the foregoing clinical experiments in healthy men and women indicate that 1) the nonequilibrium GH t 1/2, (body surface area-normalized) Vo, and MCR are independent of GH dose, sex, menstrual cycle stage, and serum estradiol concentrations; 2) the GH t 1/2 calculated after iv bolus injection is significantly (50%) shorter than that assessed during or after steady-state GH infusions or endogenously (overnight) by deconvolution analysis; and 3) the descending rank order of GH t 1/2 values in healthy volunteers is approximately: decay from steady state (23+/-2.3 min) > endogenously secreted GH (18+/-1.3 min) > during equilibrium infusion (15+/-1 min) > after bolus infusion (9.8+/-0.8 min). We thus conclude that for any given body surface area, the elimination properties of GH in men and women reflect predominantly the time mode of hormone entry into the circulation, rather than gender, menstrual cycle stage, or prevailing serum estradiol concentration. Accordingly, differences in serum GH concentrations in premenopausal women compared to those in young men and across the normal menstrual cycle reflect commensurate differences in pituitary GH secretion rates.

Adult↗
PubMed1999

Polyamine biosynthesis inhibitors alter protein-protein interactions involving estrogen receptor in MCF-7 breast cancer cells.

We investigated the effects of polyamine biosynthesis inhibition on the estrogenic signaling pathway of MCF-7 breast cancer cells using a protein-protein interaction system. Estrogen receptor (ER) linked to glutathione-S-transferase (GST) was used to examine the effects of two polyamine biosynthesis inhibitors, difluoromethylornithine (DFMO) and CGP 48664. ER was specifically associated with a 45 kDa protein in control cells. In cells treated with estradiol, nine proteins were associated with ER. Cells treated with polyamine biosynthesis inhibitors in the absence of estradiol retained the binding of their ER with a 45 kDa protein and the ER also showed low-affinity interactions with a number of cellular proteins; however, these associations were decreased by the presence of estradiol and the inhibitors. When samples from the estradiol+DFMO treatment group were incubated with spermidine prior to GST-ER pull down assay, an increased association of several proteins with ER was detected. The intensity of the ER-associated 45 kDa protein increased by 10-fold in the presence of 1000 microM spermidine. These results indicate a specific role for spermidine in ER association of proteins. Western blot analysis of samples eluted from GST-ER showed the presence of chicken ovalbumin upstream promoter-transcription factor, an orphan nuclear receptor, and the endogenous full-length ER. These results show that multiple proteins associate with ER and that the binding of some of these proteins is highly sensitive to intracellular polyamine concentrations. Overall, our results indicate the importance of the polyamine pathway in the gene regulatory function of estradiol in breast cancer cells.

Amidines↗
PubMed1999

Subacute sclerosing panencephalitis in a case of aqueductal stenosis.

A 14-year-old boy presented with history of deterioration of scholastic performance, altered behaviour, difficulty in walking and repeated falls since last 2-3 months. He had history of delayed milestones and at 11 months developed febrile rashes. On investigations, MRI showed compensated hydrocephalus with aqueductal stenosis. EEG suggested subacute sclerosing panencephalitis (SSPE). CSF was positive for measles antibody titre. This case of aqueductal stenosis with SSPE is very interesting for its diagnostic dilemma.

Adolescent↗
PubMed1998

Development of a model for evaluating the interaction between human pre-B acute lymphoblastic leukemic cells and the bone marrow stromal cell microenvironment.

Clonal expansion of B-cell precursor acute lymphoblastic leukemia (ALL) is potentially regulated by survival, growth, and death signals transduced by the bone marrow (BM) microenvironment. Using a human BM stromal cell culture that supports the growth of normal human B-cell precursors, we established a pre-B ALL cell line designated BLIN-2. BLIN-2 has a clonal rearrangement of the Ig heavy chain locus, a dic(9;20) chromosomal abnormality, and a bi-allelic deletion of the p16(INK4a) and p19(ARF) genes. The most interesting feature of BLIN-2 is an absolute dependence on adherent human BM stromal cells for sustained survival and growth. BLIN-2 cultured in the absence of BM stromal cells undergo apoptosis, and direct contact with viable BM stromal cells is essential for optimal growth. BLIN-2 cells also grow on vascular cell adhesion molecule-1 (VCAM-1)-negative human skin fibroblasts, making it unlikely that a very late antigen-4 (VLA-4)/VCAM-1 interaction is required for BLIN-2 growth. Western blot analysis of BLIN-2 cells cultured in the presence or absence of BM stromal cells demonstrates that contact of BLIN-2 with BM stromal cells induces hyperphosphorylation of Rb. In contrast, the pre-B ALL cell line BLIN-1, which has a bi-allelic deletion of p16(INK4a) p19(ARF) but does not require BM stromal cells for growth, does not undergo Rb phosphorylation after BM stromal cell contact. The BLIN-2 cell line will facilitate identification of ligand/receptor interactions at the B-cell precursor/BM stromal cell interface and may provide new insight into microenvironmental regulation of leukemic cell survival and growth.

Apoptosis↗
PubMed1998

Graft permeabilization facilitates gene therapy of transplant arteriosclerosis in a rabbit model.

BACKGROUND: Smooth muscle cell (SMC) replication plays a central role in the pathogenesis of transplant arteriosclerosis. One strategy to eliminate dividing cells is to express a herpesvirus thymidine kinase (tk) gene that phosphorylates the nucleoside analogue ganciclovir into a toxic form leading to cell killing. However, medial SMCs are resistant to gene transfer unless the artery undergoes deendothelialization. We hypothesized that manipulations that increase the "porosity" of the artery can make SMCs prone to gene transfer without denudation. METHODS AND RESULTS: In organ culture of rabbit aorta, longitudinal stretch and supraphysiological pressure applied for 3 hours during incubation with adenoviral vector facilitated gene transfer into medial SMCs without denudation. Of the SMCs, 10.2+/-3.8% expressed a reporter gene of human placental alkaline phosphatase (hpAP), whereas SMCs in control arteries did not express hpAP. To evaluate the feasibility of transgene expression in arterial grafts, we performed such permeabilization-assisted reporter gene transfer into aortas of donor Dutch Belted rabbits and transplanted them into carotid arteries of recipient New Zealand White rabbits. Unstretched transfected grafts were used as a control. SMCs expressed hpAP (7. 3+/-2.4% of cells in 2 days and 4.2+/-1.9% in 2 weeks) in stretched grafts only. In the next series of experiments, we transfected stretched grafts with ADV-tk and combined transplantation with systemic administration of ganciclovir. Stretched ADV-hpAP grafts were used as a control. In 2 weeks, the formation of intimal thickening in tk-expressing grafts was significantly reduced (P<0. 01) because of a decrease in proliferating SMCs. CONCLUSIONS: Manipulations within target tissues can enhance the efficiency of gene transfer into SMCs. Although mechanical permeabilization is clinically problematic, in principle, targeting SMC replication may provide a genetic approach to the treatment of transplant arteriosclerosis.

Adenoviridae↗
PubMed1998

Examination of wear in Duraloc acetabular components: two- to five-year evaluation of Hylamer and Enduron liners.

To help increase the longevity of polyethylene components used in total joint arthroplasty, new forms of ultrahigh molecular weight polyethylene (UHMWPE) have been developed. This study reports on the in vivo performance of Hylamer (DePuy DuPont Orthopaedics, Newark, DE), a high crystalline form of UHMWPE, and on the performance of conventional Enduron polyethylene (DePuy, Warsaw, IN). With the use of a specially designed computer system, the time course of two-dimensional femoral head penetration into 80 Hylamer and 140 Enduron acetabular liners in situ from two to five years was compared. At the most recent follow-up (mean, 3.6 years), the rate of femoral head penetration into the Hylamer liners was lower than the rate of head penetration into the Enduron liners (0.15 mm/year versus 0.20 mm/year, P = . 10). Temporal analysis revealed that the Hylamer liners had lower penetration rates than those of the conventional polyethylene liners in the first three postoperative years, but that head-penetration rates between the two groups became similar with increased time in situ. Continued examination of both types of polyethylene components is imperative before conclusions on long-term performance can be drawn.

Acetabulum↗
PubMed1998

Sacral insufficiency fractures: an unsuspected cause of low back pain.

We describe 10 cases of sacral fractures diagnosed within the rheumatology department at Southend Hospital over the last 5 yr. All presented with sudden-onset low back pain. The majority were elderly, frail, with chronic inflammatory disease (six with rheumatoid arthritis, one with polymyalgia rheumatica, one with vasculitis) and had received steroids. Diagnosis was delayed by the inability of plain radiographs to show these fractures and was ultimately demonstrated by technetium scintigraphy/computed tomography scan. We feel that this diagnosis should be considered in elderly patients with rheumatoid arthritis or other risk factors for osteoporosis who present with low back pain and sacral tenderness. Further clues may be parasymphyseal tenderness (suggesting associated pubic ramus fracture), elevated alkaline phosphatase and plain radiograph showing pubic ramus fractures or parasymphyseal sclerosis. Patients with this complication generally have a poor prognosis and two of our patients have died. Seven required in-patient stay (mean 20 days; range 14-41). The mortality, morbidity and costs incurred in management may be comparable to those of femoral neck fractures.

Aged↗
PubMed1998

Role of chewing and smoking habits in the etiology of oral submucous fibrosis (OSF): a case-control study.

Oral submucous fibrosis (OSF), a premalignant and crippling condition of the oral mucous membrane, was studied to identify its relationship to various chewing and smoking habits. Two hundred and thirty-six consecutive cases of OSF were compared with 221 control subjects matched for age, sex and socio-economic conditions. It was found that chewing of areca nut/quid or pan masala (a commercial preparation of areca nuts, lime, catechu and undisclosed colouring, flavouring and sweetening agents) was directly related to OSF. Also, pan masala was chewed by a comparatively younger age group and was associated with OSF changes earlier than areca nut/quid chewing. However, chewing or smoking tobacco with various other chewing habits did not increase the risk of developing OSF. It was also found that frequency of chewing rather than the total duration of the habit was directly correlated to OSF.

Adolescent↗
PubMed1998

Asthma and epilepsy: are they related? A retrospective study.

Numerous studies have suggested that epilepsy and asthma may be related conditions. There has, however, been little epidemiologic data published to support this association. We conducted a retrospective study to determine whether the prevalence of epilepsy is increased among children with asthma, and the prevalence of asthma is increased among children with epilepsy, in comparison with the general pediatric population. We reviewed the medical records, at a large city hospital, of two groups of pediatric outpatients: (1) 400 consecutive patients with asthma followed regularly at the asthma and allergy clinic; and (2) 201 consecutive patients with idiopathic epilepsy followed regularly at the pediatric neurology clinic. Patients with a history of birth prior to 36 weeks' gestational age were excluded. Among the 400 cases of asthma, there were three patients with idiopathic epilepsy (prevalence of 0.75%). The prevalence of epilepsy was similar in mild (0.79%) and moderate-to-severe (0.73%) asthma. Among the 201 cases of idiopathic epilepsy, there were 12 patients with asthma (prevalence of 5.97%). Similar percentages of epilepsy patients with and without asthma reported generalized tonic-clonic, complex partial, simple partial, and myoclonic seizures as their predominant type. The prevalence values in this study are consistent with the prevalence of epilepsy and asthma in the general pediatric population. Our findings therefore suggest that idiopathic epilepsy and asthma are not etiologically related or mutually predisposing conditions. Small samples, failure to exclude patients born prematurely, and the equation of electroencephalographic (EEG) abnormalities with epilepsy may account for the results of previous studies.

Asthma↗
PubMed1998

Generalized odontodysplasia--a case report.

Odontodysplasia is a relatively uncommon condition that can affect both primary and permanent dentition. It is characterized by defective formation of both enamel and dentin, with enlarged pulp chambers and root canals with open apices. It is usually a localised condition where one or few teeth may be involved. Sometimes, an entire quadrant or more than one quadrant may be involved but generalized involvement is extremely rare. An interesting case of a generalized odontodysplasia affecting both primary and permanent dentition in an eight year old girl is presented here.

Child↗