Human origins and analysis of mitochondrial DNA sequences.
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Africa↗
Biomedical subjects
S Kumar
Publications and source records attributed to S Kumar.
Protection against 7,12-dimethylbenzanthracene-induced tumour initiation by protein A in mouse skin.
Protein A is an immunostimulating glycoprotein obtained from Staphylococcus aureus Cowan I. Its antitumour activity is proven in various tumour models. Its ability to provide protection against tumour initiation by the chemical carcinogen 7,12-dimethylbenzanthracene (DMBA) has been investigated in the present study using a mouse skin model of two-stage carcinogenesis. Protein A was administered intraperitoneally (1 microgram/animal 20 g body wt.) twice a week for 2 weeks, prior to initiation by DMBA. The promotion was performed by twice weekly applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA) (3 or 5 micrograms/animal in 100 microliters acetone). Protein A provided significant protection to animals from DMBA-induced tumour initiation as was observed by the decrease in cumulative number of tumours, percent of animals developing tumours, number of tumours per animal and rate of tumour growth. Our data indicate that protein A has anticarcinogenic properties.
9,10-Dimethyl-1,2-benzanthracene↗
Circulatory half-life but not interaction with the lutropin/chorionic gonadotropin receptor is modulated by sulfation of bovine lutropin oligosaccharides.
Certain of the glycoprotein hormones, including bovine lutropin (bLH), bear asparagine-linked oligosaccharides terminating with the sequence SO4-4GalNAc beta 1-4GlcNAc beta 1-2Man alpha. To establish the biologic significance of these sulfate-bearing oligosaccharides we have compared properties of native bLH, desulfated bLH, recombinant bLH produced in Chinese hamster ovary cells that bears asparagine-linked oligosaccharides terminating with sialic acid alpha 2- 3Gal beta 1-4GlcNAc beta 1-2Man alpha rather than sulfated oligosaccharides (bLH/CHO), and desialyzed bLH/CHO. Using cultured MA-10 cells, a Leydig cell tumor line expressing the lutropin/chorionic gonadotropin receptor, we have found no differences in binding, cAMP production, or progesterone production between native and desulfated bLH. Sulfation of bLH oligosaccharides does not, therefore, modulate bLH bioactivity at the level of the lutropin/chorionic gonadotropin receptor. Removal of sulfate from bLH oligosaccharides and sialic acid from bLH/CHO oligosaccharides results in rapid clearance from the circulation by the hepatocyte asialoglycoprotein receptor. Thus sulfate, like sialic acid, prevents clearance from the circulation by the asialoglycoprotein receptor. The rapid removal of desulfated bLH from the circulation causes a 4- to 16-fold increase in the amount of bLH required to stimulate ovulation compared with native bLH. Particularly striking were differences in the metabolic clearance rates for native bLH and bLH/CHO, 7.3% per min and 1.7% per min, respectively. These differences were unexpected because bLH and bLH/CHO do not differ significantly in charge or size. The different metabolic clearance rates obtained for bLH and bLH/CHO indicate that the presence of sulfated rather than sialylated oligosaccharides on bLH results in a shorter circulatory half-life, which has a significant impact on in vivo bioactivity.
Animals↗
Necrosis and inhibition of growth of human lung tumor by anti-alpha-human chorionic gonadotropin antibody.
Human lung tumor cells (ChaGo) established in culture from a bronchogenic squamous cell carcinoma synthesize and secrete large amounts of human chorionic gonadotropin (HCG), predominantly the alpha subunit of the glycoprotein hormone. ChaGo cells lose their transformation phenotypes following treatment with anti-alpha-HCG antibody or following inhibition of intracellular synthesis of alpha-HCG by the anti-sense RNA technique. We report that tumors induced by ChaGo cells in female athymic mice undergo necrotic degeneration following local or intraperitoneal administration of alpha-HCG-specific-antibody. The alpha-HCG antibody did not affect the growth of tumor induced by alpha-HCG nonproducing human tumor cells. Histopathological examinations of the anti-alpha-HCG antibody-treated tumor tissues showed active necrosis. When the antibody treatment was discontinued, the tumorigenesis process resumed. When anti-alpha-HCG antibody was administered simultaneously with ChaGo cells, a concentration-dependent inhibition of tumor growth in athymic mice was completely prevented at higher concentrations of the specific antibody.
Animals↗
Studies of in vitro skin permeation and retention of a leukotriene antagonist from topical vehicles with a hairless guinea pig model.
A leukotriene antagonist [Ro 23-3544; 6-acetyl-7-[5-(4-acetyl-3-hydroxy-2-propylphenoxy)pentyloxy] -3,4-dihydro-2H-1-benzopyran-2-carboxylic acid; 1] was studied in vitro for its permeation through and retention in hairless guinea pig skin from various topical vehicles. Both the free acid and the sodium salt forms of the drug were used. The vehicles evaluated were polyethylene glycol 400, propylene glycol, dimethyl sulfoxide (DMSO), C12-C15 alcohol lactates, dimethyl isosorbide, butyrolactone, methylpyrrolidone, hexyl laurate, isopropyl myristate, and caprylic/capric triglyceride (Neobee M5). For the salt form of the drug, the highest permeability coefficient and retention were obtained from DMSO and methylpyrrolidone, respectively. For the acid form, however, the highest permeability coefficient and retention were obtained from hexyl laurate and DMSO, respectively. The highest permeation and retention values were not obtained from the same vehicle for either the salt or the acid form of the drug. This observation questions the validity of using permeation (flux) measurements to screen topical drugs and formulations. Although the precise reasons for this lack of correlation between permeation and retention are not known at this time, this study has shown that the solubility parameters of the drug and the vehicles used may play an important role. It seems logical to conduct skin retention studies rather than flux measurements in evaluating drug delivery from dermatological products.
Administration, Cutaneous↗
Effect of iontophoresis on in vitro skin permeation of an analogue of growth hormone releasing factor in the hairless guinea pig model.
The shortened analogue of growth hormone releasing factor (GRF) Ro 23-7861 (1) has a molecular weight of 3929 daltons [equivalent to GRF (1-29)] and is more potent than the endogenous GRF (1-44). The in vitro hairless guinea pig model and vertical and horizontal diffusion cell assemblies were used to study the effect of iontophoresis on the permeability to skin of 1. The transport of 1 across the skin was studied by monitoring the rate of its appearance in the receiver compartment with a radioimmunoassay. No permeability of 1 was observed without iontophoresis, whereas with iontophoresis, the permeability of 1 was significant. For example, at a current density of 0.23 mA/cm2 and buffer concentration of 0.05 M, the flux of 1 was 56.8 +/- 8.21 ng/cm2.h. The flux of 1 was independent of the design of the permeation apparatus, the electrodes, the donor and receiver volumes, the type of current (constant or pulsed), and the frequency of the pulsed current. The flux of 1 increased curvilinearly with the increase in salt concentration of the buffer and linearly with the increase in current.
Algorithms↗
Nasal delivery of [14C]dextromethorphan hydrochloride in rats: levels in plasma and brain.
Dextromethorphan (DM) is a neuroprotective agent. The mechanism of action is believed to be by N-methyl-D-aspartate receptor blockade. The concentration of DM in the brain is believed to be dose and route dependent. Delivery by the nasal route has received a lot of attention recently, because drug absorption from this route follows intravenous profiles with no first-pass effect. The uptake of DM in the brain from the nasal route was 65.9% compared with the intravenous route, whereas the plasma bioavailability from the nasal route was 78.8%. The nasal route is a viable alternative to the parenteral route for DM administration.
Absorption↗
A monoclonal antibody (E-9) binds preferentially to the vasculatures of human tumors, embryonic and regenerating tissues.
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Adult↗
Antiangiogenesis strategies in cancer therapy with special reference to Krestin.
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Alkaline Phosphatase↗
Double traumatic caroticocavernous fistula and its treatment by detachable balloons.
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Adolescent↗
Hepatitis C virus does not cause nonalcoholic steatohepatitis.
The pathogenesis of nonalcoholic steatohepatitis (NASH) remains poorly understood. Since inflammation and fatty changes are associated with hepatitis C (HCV) infection, we have tested the role of HCV in the genesis of NASH. Five consecutive cases of classic NASH were tested by Abbott anti-c100-3 EIA and polymerase chain reaction (PCR) to detect HCV-RNA. All serum specimens were negative for anti-c100-3 (or anti-HCV EIA) and HCV PCR. Based on this study, we conclude that HCV does not play a causative or contributing role in the pathogenesis of NASH.
Adult↗
The partial characterization of proteases present in the excretory/secretory products and exsheathing fluid of the infective (L3) larva of Necator americanus.
Following the observation that live third-stage larvae (L3) could digest gelatin in vitro, gelatinolytic protease activity has been demonstrated at pH 8.5, in both exsheathing fluid (EF) and excretory/secretory (ES) products of infective L3 of Necator americanus. EF resolved as a single band of proteolytic activity, with a mol. wt of 116 kDa, while L3 ES products exhibited multiple bands of proteolysis, at 219, 200, 195, 166, 137, 92, 72 and 62 kDa; weak bands were detectable at 92 and 72 kDa. The EF protease was characterized as cysteine, whereas ES apparently possessed one serine (195 kDa) and seven (219, 200, 166, 137, 92, 72 and 62 kDa) cysteine protease bands and a combination of metallo- and cysteine proteases of approximately the same mol. wts (62, 137 and 219 kDa). Though EF was not able to cleave immunoglobulins, ES was shown to cleave IgG, IgA and IgM, but not IgD or IgE. The activity appeared to be directed toward the Fc portion of the molecule, and was inhibited by PMSF, which is indicative of serine protease activity. The significance of the presence of such apparently diverse proteases in larval products is discussed.
Animals↗
Skin penetration by ensheathed third-stage infective larvae of Necator americanus, and the host's immune response to larval antigens.
In vitro experiments were conducted to assess skin penetration by ensheathed third-stage infective larvae (L3) of Necator americanus. The fact that only a small proportion of larval sheaths was recoverable from the outer skin surface suggested that some larvae penetrate mouse skin without undergoing exsheathment. Penetration by ensheathed larvae was confirmed visually using a novel fluorescein isothiocyanate (FITC)-labelling technique in which viable ensheathed larvae were fluoresceinated, applied onto intact mouse skin, and their progress monitored in frozen skin sections. This direct observation that the L2-derived sheath can present antigens to the host's immune system was also monitored by immunoassay to provide confirmatory information regarding skin penetration by ensheathed larvae. Sera from humans infected with Necator americanus were shown to react in ELISA against antigens stripped by detergent (cetyltrimethylammonium bromide) from the sheath surface, and with antigens contained in L3-exsheathing fluid. These data suggest that the host's immune response, as a result of antigenic stimulation by the cast sheath and exsheathing fluid, could in fact be diverted away from the potentially vulnerable L3 stage.
Animals↗
Calcium, calmodulin and 3',5'-cyclic nucleotide phosphodiesterase activity in human muscular disorders.
3',5'-Cyclic nucleotide phosphodiesterase (PDE) is known to play an important role in the regulation of cyclic nucleotide levels in various tissues including the muscle. Previous studies have estimated the level of this enzyme in several neuromuscular disorders but the results have been variable. Moreover, there was no attempt made to correlate the enzyme levels with the levels of calcium and calmodulin, both of which regulate diverse biological processes including muscle contraction. In the present study we have estimated phosphodiesterase in the muscle of normal controls as well as patients with myotonic (MyD) and Duchenne muscular dystrophy (DMD) and amyotrophic lateral sclerosis (ALS). PDE was found to be increased significantly in all of the diseased muscles as compared to controls (P less than 0.01). But the increase could be coupled with an increase in calcium and calmodulin only in Duchenne dystrophic muscle.
3',5'-Cyclic-AMP Phosphodiesterases↗
Does hyaluronan have a role in endothelial cell proliferation of the synovium?
Hyaluranate (HA) is a major constituent of synovial fluid, but its concentration and molecular size differ in normal and inflamed joints. HA can induce or inhibit angiogenesis depending on both its size and its concentration. Endothelial-cell endocytose-labeled macromolecular HA and HA oligosaccharides and binding studies have identified an HA-specific receptor on the endothelial cell surface (KD, 10(-10) mol/L; approximately 2,000/cell). The molecular weight of HA-binding proteins was found to be 90 to 125, 78, and 46 kd.
Animals↗
Cardiac involvement in non-specific aorto-arteritis.
Cardiac involvement in 75 cases (mean age 21.1 +/- 6 years) with non-specific aorto-arteritis was studied. Detailed clinical examination, echocardiography and cardiac catheterization, including angiography, were done in all the cases, as was coronary angiography. Features of cardiac failure like sinus tachycardia, cardiomegaly, left ventricular third heart sound gallop and pulmonary congestion were detected in 27 cases with reduction of left ventricular ejection fraction (25-48%). Systemic hypertension was seen in 60 cases. Central aortic pressure, left ventricular systolic pressure and left ventricular end-diastolic pressure were increased in 66 cases. Pulmonary hypertension and increased pulmonary vascular resistance were detected in 6 cases. Aortic and mitral regurgitation were seen in 15 and 12 cases, respectively. Three patients had features of dilated cardiomyopathy such as generalized cardiomegaly, systemic and pulmonary congestion but without any cardiac murmurs and with normal central aortic pressure. The coronary angiogram revealed obstruction of the left anterior descending artery in 3 cases and right coronary artery obstruction in another 3 cases. Histopathological studies revealed non-specific inflammatory changes with fibrosis in cardiac musculature and the great vessels.
Adolescent↗
Epidermoid cyst in association with subcutaneous meningioma.
A 17-year-old female presented with a non-tender, firm and fixed swelling in the right frontal region. Skull x-rays revealed soft tissue shadow and mild hyperostosis of the underlying frontal bone. Histopathological examination after excision showed it to be a meningioma with an epidermoid cyst.
Adolescent↗
Ontogeny of glycerol phosphate dehydrogenase-positive oligodendrocytes in rat brain. Impaired differentiation of oligodendrocytes in the myelin deficient mutant rat.
The ontogeny of oligodendrocytes in the myelin deficient (md) rat mutant and in control rats was explored immunohistochemically using an antiserum against the oligodendrocyte specific enzyme, glycerol phosphate dehydrogenase (GPDH), and the avidin-biotin complex technique. In control rats, GPDH was demonstrated to be expressed relatively early in oligodendrocyte differentiation, prior to either myelin basic protein or proteolipid protein expression. With development, oligodendrocytes containing GPDH increased in number, apparent staining intensity, cell soma area and process elaboration. Fewer GPDH+oligodendrocytes were observed in the brain of mutant rats than in unaffected littermates at all developmental ages, and major developmental increases in oligodendrocyte density were delayed. The density of GPDH+oligodendrocytes was reduced by about 40% in both the corpus callosum and in the cingulate cortex of P22-25 and mutants compared with control rats. The oligodendrocyte cell soma area was not influenced by the md condition, and increased 2-fold with development in rats of both genotypes. The area of coronal sections occupied by the corpus callosum increased about 2.5-fold with development, and was 30% smaller in mutant rats late in their lifespan than in unaffected littermates. The reductions in oligodendrocyte density reported here are of insufficient magnitude to fully account for biochemically measured reductions in oligodendrocyte gene expression accompanying the md trait, indicating that gene expression per oligodendrocyte is also impaired. Cell counts in control rats also revealed that oligodendrocytes are overproduced during development. Cell density and the total number of corpus callosum GPDH+oligodendrocytes per section were maximal at P22-25 and then decreased to adult values. These results suggest that glial cells, like neurons, may be generated in excessive numbers, and some subsequently die, as a normal concomitant of development.
Aging↗