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Biomedical subjects

P Ghosh

Publications and source records attributed to P Ghosh.

At least 271 records · Page 15Linked to original sources
PubMed1990

Neurokinin A levels in the hypothalamus of rats and mice: effects of castration, gonadal steroids and expression of heterologous growth hormone genes.

Neurokinin A is a decapeptide with pharmacological activities and localizations similar to those of substance P. In this report we describe the effects of castration and administration of testosterone, dihydrotestosterone and estradiol, on neurokinin A levels in the hypothalamus of male rats. The effects of estradiol and testosterone on hypothalamic neurokinin A were also examined in normal mice and in transgenic mice carrying the genes for human or bovine growth hormone (hGH, bGH, respectively). Either acute or prolonged castration was followed by a decrease of neurokinin A concentrations in the hypothalamus of male rats. The substitutive administration of testosterone propionate or estradiol benzoate for 14 days resulted in an increase of hypothalamic neurokinin A levels above the values found in intact animals. A lower dose of testosterone propionate or dihydrotestosterone also increased hypothalamic neurokinin A levels in the hypothalamus of castrated rats. In normal intact male mice a single injection of estradiol benzoate significantly increased hypothalamic neurokinin A levels. A similar effect was observed in transgenic mice carrying the bGH gene with phosphoenolpyruvate carboxykinase (PEPCK) promoter, while mice carrying the hGH gene failed to show any response to estradiol. In castrated male mice, either normal or transgenic, carrying the bGH gene with metallothionein promoter, a single injection of testosterone propionate significantly increased neurokinin A levels in the hypothalamus. It is concluded that sex steroids may regulate the levels of neurokinin A in the hypothalamus of rats and mice.

Animals↗
PubMed1990

Impairment of the regulation of gonadal function in Channa punctatus by metacid-50 and carbaryl under laboratory and field conditions.

Regulation of gonadal function by gonadotropic hormone (GtH) and gonadotropin-releasing hormone (GnRH) in Channa punctatus was significantly affected by nonlethal levels of Metacid-50 and Carbaryl. Under laboratory conditions, the time-dependent decrease in serum GtH level was higher in Carbaryl-treated fish than in Metacid-50-treated fish. The situation was reversed in the field, with a higher inhibitory effect of Metacid-50 being recorded. On the other hand, pituitary GtH content and GnRH activity were inhibited to a greater extent by Metacid-50 than by Carbaryl under both field and laboratory conditions. The present findings highlight that even low doses of Metacid-50 and Carbaryl are effective enough to cause reproductive damage, as evidenced by homeostatic unbalance of the reproductive regulatory system.

Animals↗
PubMed1990

The influence of weight-bearing exercise on articular cartilage of meniscectomized joints. An experimental study in sheep.

Unilateral medial meniscectomy was undertaken in 29 purebred adult merino sheep. Arthrotomy (without meniscectomy) was conducted in 11 animals, and six were used as nonoperated controls. All animals were followed with either three- or six-month active or passive postoperative management. Active animals traversed a total of 360 km after three months and 1040 km after six months. The passive group was housed in pens allowing limited weight-bearing exercise. After death, morphologic changes were recorded and cartilages from the medial and lateral joint regions were examined for water, collagen, and proteoglycan (as hexuronate) content. Proteoglycan aggregation and extractability under nondissociative (0.4 molar GuHCl) and dissociative (4.0 molar GuHCl) conditions were also determined. The collagen content of the medial cartilage of the passively maintained meniscectomized animals was reduced, relative to external controls. Although proteoglycan content was elevated in medial cartilage of the passive group three months postoperatively, these levels returned to the control range after six months. However, low-salt (0.4 molar GuHCl) extractability of proteoglycans still remained high. All cartilages of control and meniscectomized joints showed an elevation of proteoglycan content in the active groups three months postoperatively. The cartilages in the medial region of meniscectomized animals showed the largest increase, but these levels declined after six months. Proteoglycan aggregation and water content were still elevated relative to controls six months postoperatively. The collagen levels in the three-month or six-month actively maintained meniscectomized group were not distinguishable from control values. Morphologically, joints of the passively and actively maintained animals showed focal surface fibrillation and erosions. However, in the active group, osteophytes were common and well developed six months postoperatively. These studies indicate that, while weight-bearing exercise after meniscectomy appears to be beneficial to the quality of the cartilaginous matrix, it is also accompanied by osteophytosis and cartilage hyperplasia.

Animals↗
PubMed1989

Glycogen synthesis in the obliquely striated muscle of Ascaris suum.

A glycogen synthase, designated GS II, which occurs in a protein/carbohydrate complex has been purified from Ascaris suum muscle. The purified GS-II complex which is eluted from concanavalin-A--Sepharose contains proteins with Mr 140,000 and 66,000 and a glycoprotein with a carbohydrate/protein mass ratio of 3:1. GS II activity was totally dependent on glucose 6-phosphate, but exogenous glycogen was not required for polysaccharide synthesis. The GS-II complex was not phosphorylated by cyclic-AMP-dependent protein kinase, and antibodies to the protein and carbohydrate components of GS II did not cross react with the purified cyclic-AMP-regulated glycogen synthase (GS I) from A. suum muscle. Polysaccharide which was synthesized de novo by the complex was added to the large-molecular-mass glycoprotein in GS II. The glycogen-like character of the newly synthesized polysaccharide was confirmed by the observation that glycogen phosphorylase utilized the polymer as substrate in both the synthesis and degradation reactions. A model is discussed in which a core glycoprotein serves as the substrate for a glycogen synthase which is distinctly different from GS I.

Animals↗
PubMed1989

Biosynthesis of bacterial glycogen. Determination of the amino acid changes that alter the regulatory properties of a mutant Escherichia coli ADP-glucose synthetase.

The ADP-glucose synthetase of Escherichia coli K12 mutant 618 has a higher apparent affinity for the activator, fructose 1,6-P2 and a lower apparent affinity for the inhibitor, 5'-AMP, than the normal enzyme. The structural gene, glgC, of the mutant enzyme has been cloned and sequenced (Lee, Y. M., Kumar, A., and Preiss, J. (1987) Nucleic Acids Res. 15, 10603). Substitutions in the mutant enzyme were amino acid residues 296 (Lys to Glu) and 336 (Gly to Asp). Single mutant enzymes, Glu296 and Asp336, were constructed using oligonucleotide-directed mutagenesis. The Glu296 enzyme had the same allosteric kinetic constants as the wild type enzyme. The Asp336 enzyme was catalytically defective. Thus, the mutations at 296 and at 336 separately could not account for the allosteric alterations of the mutant enzyme. A hybrid glgC gene was prepared from genes of wild type and mutant 618 glgC using DNA recombinant techniques. The C-terminal portion of mutant 618 containing Glu296 and Asp336, combined with the N-terminal portion of wild type enzyme, showed allosteric and substrate kinetics similar to mutant 618 enzyme. Thus, alteration of the normal allosteric properties in mutant 618 are due to changes of both Lys296 to Glu and Gly336 to Asp.

Chromatography, Ion Exchange↗
PubMed1989

Campylobacter pylori and duodenal ulcers: the gastrin link.

The possibility that Campylobacter pylori (CP) in the gastric antrum stimulates gastrin release in duodenal ulcer (DU) disease was examined in 31 patients. The 25 patients with antral colonisation with CP had higher basal and meal-stimulated plasma gastrin concentrations, and higher peak acid output (PAO), than did the 6 without CP in the autumn.

Adult↗
PubMed1989

An enzyme-linked immunosorbent-inhibition assay for quantitation of hyaluronan (hyaluronic acid) in biological fluids.

An enzyme-linked immunosorbent-inhibition assay for quantitation of hyaluronic acid (HA) is described. The principle of the method depends on the specific binding of HA to the hyaluronic acid-binding region (HABR) of proteoglycan (PG) monomers. The remaining uncomplexed PG monomers were determined by incubation with specific monoclonal antibodies to HABR followed by addition of polyclonal antibodies against PG monomers and enzyme-conjugated antibodies. The HA in samples was quantified by comparing their inhibitory capacity in the assay against a standard inhibition curve obtained using highly purified HA. This method was used to quantitate HA at nanogram levels in normal sera and synovial fluids. The level in normal human sera was found to be 28 +/- 17 ng/ml which compared favorably with values obtained using a commercial radioassay kit on the same samples. The assay was used to measure HA in synovial fluid from patients with rheumatoid and osteoarthritis and the results obtained were comparable with data published by others.

Animals↗
PubMed1989

Isolation and characterisation of a neutral proteinase from the canine intervertebral disc.

A neutral proteinase of 94 kDa capable of degrading gelatin, canine disc proteoglycan, and L-lysine and L-arginine peptide substrates has been isolated from the greyhound intervertebral disc. Strong inhibition of this proteinase with class-specific inhibitors, such as APMSF, TLCK and benzamidine indicated a 'serine'-type specificity. Metallo, aspartyl- and cysteine proteinase inhibitors were devoid of significant action. Degradation of the resident canine disc proteoglycan monomer by the disc proteinase was shown to occur at the hyaluronic acid binding region, thereby diminishing its ability to aggregate with hyaluronic acid. The hydrodynamic size of the proteoglycan degradation products was only slightly less than that of the intact disc proteoglycan subunits.

Animals↗
PubMed1989

Retardation of articular cartilage degradation by glycosaminoglycan polysulfate, pentosan polysulfate, and DH-40J in the rat air pouch model.

The rat subcutaneous air pouch model was adapted to examine the in vivo degradation of implanted rabbit articular cartilage, both with and without induced air pouch inflammation, over a 7-day period. The effects of 3 drugs, glycosaminoglycan polysulfate (Arteparon), pentosan polysulfate (SP-54), and zinc-chelated pentosan polysulfate (DH-40J), on inflammation-induced cartilage degradation were also examined. Implanted articular cartilage from noninflamed air pouches showed a reduction in total proteoglycan (PG) content (as hexuronic acid), but not in PG extractability or aggregation, compared with cartilage maintained in tissue culture. The injection of peptone into the air pouch as an inflammogen caused an influx of leukocytes and plasma exudate and a reduction in implanted articular cartilage PG content, extractability, and aggregation, which was significantly greater than that which occurred in noninflamed air pouches. In vitro experiments demonstrated that peptone did not have a direct effect on cartilage PG degradation. Daily injection of Arteparon, SP-54, or DH-40J (10 mg/kg) into peptone-inflamed air pouches significantly increased the PG content, extractability, and aggregation in implanted articular cartilage, compared with that in cartilage from non-drug-treated control animals. The infiltration of leukocytes into the peptone-inflamed air pouches was significantly reduced by daily administration of Arteparon, 10 mg/kg. At an equivalent dose, DH-40J increased leukocyte numbers in the pouch fluid, whereas SP-54 had no significant effect on leukocyte accumulation.

Animals↗
PubMed1989

Application of an enzyme-linked immunosorbent-inhibition assay to quantitate the release of KS peptides into fluids of the rat subcutaneous air-pouch model and the effects of chondroprotective drugs on the release process.

The effects of the chondroprotective agents (Arteparon, SP-54 and DH40J) on the release of proteoglycan degradation products (as keratan sulphate peptide fragments) from articular cartilage implanted into rat subcutaneous air pouches have been investigated by using an enzyme-linked immunosorbent-inhibition assay (ELISIA). The ELISIA technique was capable of quantitating the keratan sulphate peptides (KS peptides) in fluids within the range of 100-2,000 ng/ml by using the monoclonal antibody line 1/20/5-D-4 and human articular cartilage KS peptides as standard reagents. It was found that the levels of KS peptides present in the air-pouch fluid of rats treated with the chondroprotective drugs was significantly less than in fluid aspirated from the pouches of non-drug-treated control animals. On the basis of these findings we suggest that the assessment of KS peptide by ELISIAs may provide a useful means of monitoring proteoglycan breakdown products in biological fluids (e.g. synovial fluids or blood) and for evaluating the effects that antiarthritic drugs may have on this process.

Animals↗
PubMed1989

Evaluation of the effect of antiarthritic drugs on the secretion of proteoglycans by lapine chondrocytes using a novel assay procedure.

A new method is described for separating free 35SO4-- from 35SO4 labelled proteoglycans synthesised by rabbit articular chondrocytes cultured in the presence of excess 35SO4--. The procedure uses the low solubility product of barium sulphate to remove, by precipitation, free 35SO4-- from culture medium. Optimum recovery of 35SO4 labelled proteoglycans was achieved after papain digestion to release 35SO4-glycosaminoglycans, and addition of chondroitin sulphate before the precipitation step. Using this assay, we studied the effect of six drugs-indomethacin, diclofenac, sodium pentosan polysulphate, glycosaminoglycan polysulphate ester, tiaprofenic acid, and ketoprofen-on the secretion into the medium of labelled proteoglycans by lapine chondrocytes. The six drugs were tested at 0.1, 1, 10, 50, and 100 micrograms/ml over four consecutive 48 hour culture periods. A consistent concentration-response pattern was found for the four non-steroidal anti-inflammatory drugs (NSAIDs) studied. Generally they inhibited proteoglycan secretion at 50 and 100 micrograms/ml but had no effect at lower concentrations. Inhibition of secretion was strongest with indomethacin and diclofenac at 50 and 100 micrograms/ml. In contrast with the NSAIDs studied, the two sulphated polysaccharides (sodium pentosan polysulphate and glycosaminoglycan polysulphate ester) at low concentrations increased proteoglycan secretion by chondrocytes, with maximal stimulation occurring at 1 microgram/ml. Sodium pentosan polysulphate, but not glycosaminoglycan polysulphate ester, showed inhibitory activity at 50 and 100 micrograms/ml.

Animals↗
PubMed1989

Lysozyme, a major low-molecular-weight cationic protein of the intervertebral disc, which increases with ageing and degeneration.

Lysozyme was demonstrated to increase in content in the human intervertebral disc in a significant age-dependent manner. In young discs (less than 20 years) the levels were 440 U/g wet weight, whereas in older discs (greater than 65 years) the concentration was 3,460 U/g wet weight. These findings contrasted with the hexuronate level (as a marker of proteoglycans) and neutral sugar content of the tissues which decreased with age. The level of lysozyme determined in the disc tissue also correlated with the morphological grade of disc degeneration.

Adolescent↗
PubMed1989

Pentosan polysulfate (Cartrophen) prevents the hydrocortisone induced loss of hyaluronic acid and proteoglycans from cartilage of rabbit joints as well as normalizes the keratan sulfate levels in their serum.

The intraarticular injection of a sterile solution of 25 mg hydrocortisone succinate into rabbit knee joints once a week for 8 weeks reduced the levels of proteoglycans and hyaluronic acid (HA) in articular cartilage. In contrast, the keratan sulfate (KS) peptide levels present in sera of these animals were elevated relative to a saline treated control group. By injecting 25 mg hydrocortisone succinate combined with pentosan polysulfate (Cartrophen) (5 mg) into rabbit joints over the 8 week period, the loss of proteoglycans and HA from articular cartilage was abrogated and serum KS-peptides were restored, with time, to within control levels. These findings suggest that intraarticular administration of high dose hydrocortisone succinate to rabbits has a deleterious effect on articular cartilage HA and proteoglycan metabolism but this effect can be attenuated by co-intraarticular administration of Cartrophen.

Animals↗