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Biomedical subjects

C Prasad

Publications and source records attributed to C Prasad.

At least 37 records · Page 2Linked to original sources
PubMed2000

Kyphomelic dysplasia: a rare form of semilethal skeletal dysplasia.

Kyphomelic dysplasia is a rare form of generalized skeletal dysplasia with about 15 cases described so far in the literature. We present the clinical, radiological, and pathological findings of an antenatally detected female fetus affected with this disorder. The differential diagnoses of prenatal and perinatal semilethal skeletal dysplasias and salient features of documented cases of kyphomelic dysplasia are presented.

Bone Diseases, Developmental↗
PubMed1999

Propylthiouracil-induced hypothyroidism reduces xenograft tumor growth in athymic nude mice.

BACKGROUND: Thyroid hormones are endocrine modulators of several vital processes that are crucial to tumor growth and differentiation. Several anecdotal reports in the literature suggest that some histologic types of carcinoma may remain in a dormant state for prolonged periods of time in patients with hypothyroidism, with eventual progression of the disease once the decreased thyroid function is identified and corrected. METHODS: Oral propylthiouracil (PTU) was used to induce hypothyroidism in athymic nude mice that were subsequently inoculated with lung adenocarcinoma and prostate adenocarcinoma cells. Mice were also treated with a combination of PTU and thyroxine, which resulted in hyperthyroid levels of T(4). RESULTS: Subcutaneous lung and prostate xenografts grew significantly more slowly in hypothyroid mice treated with PTU than in euthyroid or hyperthyroid mice, regardless of treatment with PTU. Tumors grew well in groups of mice that were changed from a hypothyroid state to a euthyroid state by withdrawal of oral PTU. Administration of PTU 3 weeks after tumor inoculation also caused the tumor growth to slow significantly compared with tumors in mice that did not receive PTU. Mice that received PTU and thyroxine had tumors that grew as well as the tumors in euthyroid control animals. CONCLUSIONS: Our study indicates that human lung and prostate tumors do not grow well in hypothyroid nude mice, and that rendering these animals euthyroid has a significant impact on the growth rate of these tumors. Furthermore, in vitro and in vivo data indicated that this was not a result of an interaction of the tumor cells with PTU, but rather a result of the hypothyroid state.

Animals↗
PubMed1999

Isolation, characterization, and distribution of a 24-kDa proteoglycan in the urine of cachectic cancer and AIDS patients.

Substantial weight loss in individuals with AIDS or cancer is associated with a poor prognosis and increased mortality. We have isolated and partially characterized a proteoglycan (named azaftig) from the urine of a cancer patient experiencing weight loss. Furthermore, we have raised a polyclonal antibody to azaftig in rabbits and developed a procedure to measure the level of this proteoglycan in urine by Western blot. We report the presence of azaftig in the urine of cancer and AIDS patients experiencing weight loss, but not in the control or weight-stable subjects. The azaftig-like immunoreactivity was present in 69.2% (9/13) of patients with weight loss, but only in 27.0% (3/11) of weight-stable cancer or AIDS patients and none of the control subjects (n = 8).

Adult↗
PubMed1999

Azaftig, a urinary proteoglycan from a cachectic cancer patient, causes profound weight loss in mice.

Cachexia is a complex medical condition characterized by significant weight loss associated with decreased body fat and protein; the condition may present itself with or without anorexia. We have isolated and partially characterized a proteoglycan (azaftig) from the urine of cancer and AIDS patients experiencing weight loss. When given to mice, the purified azaftig resulted in a significant decrease in body weight and body fat without any effect on appetite. The results of these studies show that azaftig may be one of the many factors participating in the emergence of the cachectic state.

Acquired Immunodeficiency Syndrome↗
PubMed1999

On the nature and distribution of enterostatin (Val-Asp-Pro-Asp-Arg)-like immunoreactivity in rat plasma.

Enterostatins, pentapeptides represented at the amino-terminus of the procolipase molecule, are derived following tryptic cleavage of the procolipase molecule in the lumen of the gut. Val-Pro-Asp-Pro-Arg or VPDPR is one such enterostatin. Despite pharmacologic studies suggesting a role for VPDPR in appetite regulation and insulin secretion, the function of this endogenous peptide has been impossible to discern due to the lack of a suitable assay. Using polyclonal antibodies raised against VPDPR and different chromatographic methods, we examined the nature and distribution of enterostatin-like immunoreactivity in rat plasma. The results reported here show for the first time the presence of VPDPR-like immunoreactivity in rat plasma. Further characterization of the plasma VPDPR-like immunoreactivity revealed that a) it is not due to APGPR, VPGPR, or VPDPR but to another peptide similar to VPDPR, and b) plasma VPDPR-like immunoreactivity may circulate bound to large carrier proteins.

Animals↗
PubMed1999

Thyrotropin releasing hormone stimulation of GABA-gated but not basal chloride ion influx in rat cerebellum.

Potential interaction between gamma-amino butyric acid (GABA) and thyrotropin-releasing hormone (TRH) in eliciting a variety of central nervous system (CNS)-related biologic activities is well known; however, the mechanism underlying this interaction is not clearly defined. To gain further insight into this interaction, we examined the effects of TRH and two of its central nervous system selective analogs, DN 1417 and TA 0910, on basal and GABA-mediated chloride ion influx into rat cerebellar neurosynaptosomes. The results of these studies show that TRH may facilitate GABA action by augmenting chloride ion influx and hyperpolarization of cerebellar neurons.

Animals↗
PubMed1999

Neurons exhibiting dopamine D2 receptor immunoreactivity in the substantia nigra of the mutant weaver mouse.

Neurons exhibiting D2 receptor-like immunoreactivity were investigated in the substantia nigra pars compacta of weaver mice at the light and electron microscope levels using immunocytochemical techniques. At the light microscope level, there was significant loss of D2-like immunoreactive cells in weaver mice and the remaining labeled cells exhibited less intense immunoreactivity. At the ultrastructural level, there was a decrease in the number of immunoreactive profiles and fewer synapses were observed abutting labeled dendritic profiles. In addition, degenerative changes were noted in some of the D2 receptor-like immunoreactive profiles. Double labeling with D2 and tyrosine hydroxylase indicated that the majority of the labeled profiles were double labeled. Eight-week-old homozygous weavers were paired with wild-type littermates as controls and perfused with a buffered solution of acrolein/paraformadehyde. Midbrain sections were reacted immunocytochemically either with an antiserum to D2 or with antisera to D2 and tyrosine hydroxylase, using a double-labeling technique. Sections were processed for light and electron microscopy by standard methods. The results of this study confirm the autoreceptor-like activity of D2 receptors on nigral dopamine neurons. The cell degeneration, down-regulation of D2 receptors, and decreased dendritic and synaptic components in the neuropil suggest that the synaptic integrity of the substantia nigra has been compromised, which in turn would affect the functional efficacy of the basal ganglia circuitry. This altered circuity is expressed in the Parkinson-like symptoms displayed by this mutant mouse.

Animals↗
PubMed1999

Recent advances in the genetics of epilepsy: insights from human and animal studies.

Progress in understanding the genetics of epilepsy is proceeding at a dizzying pace. Due in large part to rapid progress in molecular genetics, gene defects underlying many of the inherited epilepsies have been mapped, and several more are likely to be added each year. In this review, we summarize the available information on the genetic basis of human epilepsies and epilepsy syndromes, and correlate these advances with rapidly expanding information about the mechanisms of epilepsy gained from both spontaneous and transgenic animal models. We also provide practical suggestions for clinicians confronted with families in which multiple members are afflicted with epilepsy.

Animals↗
PubMed1999

Abundance of cyclo (His-Pro)-like immunoreactivity in the brain of TRH-deficient mice.

Cyclo(His-Pro) or CHP was initially discovered as a metabolite of thyrotropin-releasing hormone (TRH) resulting from the action of the enzyme Pyroglutamyl aminopeptidase. Physiologic and pharmacologic studies that followed this initial discovery provided indirect evidence that all CHP may not be derived from TRH. However, the recent availability of a TRH-deficient mouse has made it possible to reinvestigate whether CHP is derived from TRH. In the present study, we examined distribution of CHP and TRH in TRH-deficient mice. Northern blot analysis confirmed the absence of preproTRH mRNA in both the hypothalamus and the cortex of TRH-deficient mice. Brains from the wild-type and TRH-deficient mice were dissected into 7 regions, and TRH and CHP concentrations were determined by specific radioimmunoassay (RIA) in each region. Whereas TRH was identified in all regions of the wild-type brain, with the highest concentration in the hypothalamus, no detectable TRH was observed in any region in the TRH-deficient mice. While CHP-like immunoreactivity (CHP-LI) was present in all regions in the wild-type brain, its concentration was reduced by approximately 50% in the hypothalamus and cerebral cortex of TRH-deficient mice, with no change in other brain regions. Furthermore, the CHP-LI present in the brain of TRH-deficient mice was immunologically and chromatographically identical to synthetic CHP. These findings strongly suggest that a portion of the CHP in the brain is derived from sources other than TRH.

Animals↗
PubMed1999

Hyperenterostatinemia in premenopausal obese women.

Enterostatins [Val-Pro-Asp-Pro-Arg (VPDPR), Val-Pro-Gly-Pro-Arg (VPGPR), and Ala-Pro-Gly-Pro-Arg (APGPR)] are pentapeptides derived from the NH2-terminus of procolipase after tryptic cleavage and belong to the family of gut-brain peptides. Although enterostatin-like immunoreactivities exist in blood, brain, and gut, and exogenous enterostatins decrease fat appetite and insulin secretion in rats, the roles of these peptides in human obesity remain to be examined. To determine whether VPDPR and APGPR secretion is altered in obesity, serum VPDPR and APGPR levels were measured in 38 overnight-fasted subjects (body mass index, 17.9-54.7 kg/m2) before and after a meal. The mean fasting VPDPR in the serum of lean subjects was significantly lower than that in obese subjects [lean = 603 +/- 86 nmol/L (n = 17); obese, 1516 +/- 227 nmol/L (n = 21); P = 0.0023]. In addition, the rise in serum APGPR after a meal (postmeal/fasting ratio) was significantly higher in lean than in obese subjects [lean, 1.71 +/- 0.24 (n = 17); obese, 1.05 +/- 0.14 (n = 21); P = 0.0332]. The results of these studies show hyperenterostatinemia in obesity and a diminution in enterostatin secretion after satiety.

Adult↗
PubMed1998

Increased GABA-gated chloride ion influx in the hypothalamus of low-anxiety rats.

While it is generally accepted that y-aminobutyric acid type A (GABA(A))-receptor agonists decrease anxiety by facilitating the neuronal influx of chloride, the site of action within the brain is not clearly delineated. To gain further insight into the locus of anxiolytic action of GABA in the brain, we measured the distribution of GABA-stimulated chloride influx in seven regions of the brain from high- and low-anxiety rats. Our results show a significant increase in GABA-gated chloride influx in the hypothalamus of rats exhibiting low anxiety. The role of the hypothalamus in the regulation of anxiety is briefly discussed.

Animals↗
PubMed1998

Modulation of GABA-gated chloride ion influx in the brain by dehydroepiandrosterone and its metabolites.

Both DHEA and GABAA receptor agonists are known to reduce anxiety. Since GABAA receptor agonists are generally thought to elicit their anxiolytic effects by facilitating neuronal uptake of chloride ion, we set out to evaluate whether DHEA elicits its anxiolytic effects by a similar mechanism. The results of the studies show an uneven distribution of basal and GABA-stimulated chloride uptake in different regions (cerebellum, pons-medulla, striatum, hippocampus, mid-brain, hypothalamus and cortex) of rat brain. Contrary to our expectations, however, both DHEA and DHEAS inhibited GABA-mediated chloride uptake with DHEAS being more potent than DHEA. On the other hand, delta 4-androstenedione, another DHEA metabolite, did not have any effect on chloride uptake in any region of the brain. In conclusion, the data presented here, therefore, suggest that DHEA and DHEAS may elicit anxiolysis through mechanisms independent of GABAA receptor-mediated facilitation of neuronal chloride uptake.

Androstenedione↗
PubMed1998

Enterostatin (Val-Pro-Asp-Pro-Arg)-like immunoreactivity in rat urine: relationship to corticosterone output.

Numerous studies have documented a role for enterostatins in appetitive behavior. However, due to the lack of knowledge about the distribution of enterostatins in tissues and body fluids, it has not been possible to examine the role of endogenous enterostatin in this process. To this end, using a polyclonal antibody raised against enterostatin -- Val-Pro-Asp-Pro-Arg (VPDPR), we examined the nature and distribution of enterostatin-like immunoreactivity in the rat urine by ELISA and chromatography. The results reported here show for the first time the presence of VPDPR-like immunoreactivity (VPDPR-LI) in rat urine. Further characterization of rat urine VPDPR-LI revealed that it is not due to VPDPR but to another peptide similar to VPDPR. Furthermore, as urinary excretion of corticosterone increases, the level of VPDPR-LI in urine decreases.

Amino Acid Sequence↗
PubMed1998

Distribution and characterization of enterostatin-like immunoreactivity in human cerebrospinal fluid.

Enterostatins belong to a family of peptides (e.g., Val-Pro-Asp-Pro-Arg, VPDPR; Ala-Pro-Gly-Pro-Arg, APGPR; and Val-Pro-Gly-Pro-Arg, VPGPR) derived from the tryptic cleavage of amino-terminal pentapeptide from procolipase. Pharmacologic studies have suggested a role for these peptides in appetite regulation and insulin secretion. Studies into the distribution of enterostatins or the role of endogenous peptides have not been possible until now due to the lack of a suitable method for assay. Using two polyclonal antibodies raised against VPDPR and APGPR and different chromatographic methods, we have examined the nature and distribution of enterostatin-like immunoreactivity in human cerebrospinal fluid. The results reported here show for the first time the presence of enterostatin-like immunoreactivity in the human cerebrospinal fluid. Further characterization of cerebrospinal fluid enterostatin-like immunoreactivity revealed that it is not due to APGPR, VPGPR, or VPDPR but to another peptide similar to VPDPR.

Adult↗
PubMed1998

Limited proteolysis and physiological regulation: an example from thyrotropin-releasing hormone metabolism.

Proteases like trypsin, elastase, and many others play important regulatory functions by generating new biologically active molecules through limited proteolysis of larger proteins and peptides. The limited proteolysis of thyrotropin-releasing hormone (TRH) by Pyroglutamate aminopeptidase yields cyclo(His-Pro) or CHP, a new biopeptide associated with a variety of pharmacological activities, including regulation of body temperature, inhibition of prolactin secretion, and modulation of motor functions. Although the mechanism by which CHP elicits these biological activities is not well understood, it appears that the cyclic peptide may function at least in part by modulating central amine transport mechanisms.

Endopeptidases↗
PubMed1998

Food, mood and health: a neurobiologic outlook.

Hippocrates was the first to suggest the healing power of food; however, it was not until the medieval ages that food was considered a tool to modify temperament and mood, although scientific methods as we know them today were not in use at the time. Modern scientific methods in neuroscience began to emerge much later, leading investigators to examine the role of diet in health, including mental wellbeing, with greater precision. This review shows how short- and long-term forced dietary interventions bring about changes in brain structure, chemistry, and physiology, leading to altered animal behavior. Examples will be presented to show how diets alter brain chemistry, behavior, and the action of neuroactive drugs. Most humans and most animal species examined in a controlled setting exhibit a fairly reproducible pattern of what and how they eat. Recent data suggest that these patterns may be under the neurochemical and hormonal control of the organisms themselves. Other data show that in many instances food may be used unconsciously to regulate mood by seemingly normal subjects as well as those undergoing drug withdrawal or experiencing seasonal affective disorders and obesity-related social withdrawal. We will discuss specific examples that illustrate that manipulation of dietary preference is actually an attempt to correct neurochemical make-up.

Affect↗