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Biomedical subjects

A K Agarwal

Publications and source records attributed to A K Agarwal.

At least 19 recordsLinked to original sources
PubMed1992

Recurrence of cervical spine instability in rheumatoid arthritis following previous fusion: can disease progression be prevented by early surgery?

In a retrospective study, 110 patients with rheumatoid arthritis who had cervical spine fusion were evaluated for recurrence of cervical spine instability and resultant need for further surgery. Recurrence of cervical instability was correlated with initial radiographic abnormality, primary surgical procedure and interval between the 2 surgeries. There were 55 patients who had atlantoaxial subluxation (AAS) and required C1-C2 fusion as primary surgery. Three of these patients (5.5%) developed subaxial subluxation (SAS) and had a second procedure after a mean interval of 9 years. Twenty-two patients had AAS with superior migration of the odontoid (AAS-SMO) and had initial surgery of occiput-C3 fusion. Eight of these patients (36%) developed SAS and had a second surgery after a mean interval of 2.6 years. Of the 19 patients with primary radiographic deformity of SAS, one required further surgery for subluxation of an adjacent superior vertebra after a period of 6 years. Fourteen patients had combined deformity of AAS-SMO-SAS, and one required further surgery for SAS after an interval of 22 months. Recurrence of cervical instability following a previous fusion occurred in 15% of these 110 patients. It was seen in 5.5% of patients with initial deformity of AAS vs 36% of patients with AAS-SMO. No patients with C1-C2 fusion for AAS progressed to develop superior migration of the odontoid. We conclude that early C1-C2 fusion for AAS before development of SMO decreases the risk of further progression of cervical spine instability. The pattern of progression of cervical spine involvement, as discussed in the literature, is reviewed.

Aged↗
PubMed1992

Role of soluble factors in immune and normal sera in the control of giardiasis due to Giardia lamblia.

Hyperimmune sera (HIS), raised against crude giardia antigen, on in vitro interaction, caused more agglutination of Giardia lamblia trophozoites. Heat inactivated HIS possessed a comparable agglutinating activity as the non-inactivated controls. Non-inactivated normal (unimmunized) serum caused immobilization of Giardia trophozoite, which was checked on heat inactivation. Antibodies in immune sera are mainly responsible for agglutination, whereas the heat labile non-immune components control the mobility of the intestinal parasite.

Agglutination↗
PubMed1991

The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization.

The Type I (mineralocorticoid) receptor has identical affinities in vitro for cortisol and aldosterone. It has been suggested that the selective role of aldosterone in regulating sodium homeostasis relies on the microsomal enzyme 11 beta-hydroxysteroid dehydrogenase (11-HSD). This enzyme converts cortisol to its inactive metabolite, cortisone, preventing cortisol from binding to the Type I receptor. We have isolated human cDNA clones encoding 11-HSD from a human testis cDNA library by hybridization with a previously isolated rat 11-HSD cDNA clone. The cDNA contains an open reading frame of 876 bases, which predicts a protein of 292 amino acids. The sequence is 77% identical at the amino acid level to rat 11-HSD cDNA. The mRNA is widely expressed, but the level of expression is highest in the liver. Hybridization of the human 11-HSD cDNA to a human-hamster hybrid cell panel localized the single corresponding HSD11 gene to chromosome 1. This gene was isolated from a chromosome 1 specific library using the cDNA as a probe. HSD11 consists of 6 exons and is at least 9 kilobases long. The data developed in this study should be applicable to the study of patients with hypertension due to apparent mineralocorticoid excess, a deficiency in 11-HSD activity.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1991

Gene expression and chromatin structure in the cellular slime mold, Dictyostelium discoideum.

Micrococcal nuclease digestion of chromatin from growing cells reveals a structural organization which differs for genes transcribed at diverse rates. The late cAMP dependent prespore genes which are not transcribed in growing cells are found in growing cells in a regular nucleosomal repeat with an average spacing of 168 nucleotides. By contrast genes expressed at a low level in growing cells show an irregular pattern of bands with an average distance between bands of 80 nucleotides. The sizes of the bands generated from the transcribed genes are consistent with the concept that transcription results in the loss of the linker region histone H1 with concomitant sliding of nucleosomes to generate close packed ("slipped") di, tri, and tetra nucleosomes lacking the linker region. Further analysis of dinucleosomes released by micrococcal nuclease digestion reveals that transcriptionally active genes are found associated with dinucleosomes species which may be lacking histone H1. The length of DNA protected by these dinucleosomes is heterogeneous, ranging from 250 to 300 nucleotides. Methodology is described which has been adapted to allow two dimensional hybridization mapping of nucleoprotein complexes on single copy Dictyostelium genes.

Chromatin↗
PubMed1991

Estrogen receptor-binding affinity of tamoxifen analogs with various side chains and their biologic profile in immature rat uterus.

Estrogen receptor-binding affinity and estrogenic and antiestrogenic activity have been evaluated for tamoxifen analogs substituted with various side chains. Antagonist activity of the compounds of this series appears to be dependent on the presence of the beta-tert-aminoethoxy moiety. The results also indicate that the dissociation of these compounds from the estrogen receptor-binding site at 25 C is very slow.

Animals↗
PubMed1991

Incidence of subaxial subluxation in patients with generalized rheumatoid arthritis who have had previous occipital cervical fusions.

A retrospective study of 79 patients with rheumatoid arthritis was undertaken to determine the incidence of subaxial subluxation after upper cervical fusions. Fifty-five patients had isolated axial subluxation and underwent atlantoaxial fusion. Twenty-four underwent occipitocervical fusion for atlantoaxial subluxation and superior migration of the odontoid. The two groups were comparable in age, duration of disease, and time to follow-up (atlantoaxial fusion, 65.4 months; occipitocervical fusion, 72.6 months). Fusion rates were comparable: 80% atlantoaxial fusion and 90.1% occipitocervical fusion. Of the occipitocervical fusion patients, 36% developed subaxial subluxation requiring surgery at an average of 2.6 years after fusion. Of the atlantoaxial fusion patients, 5.5% developed subaxial subluxation requiring surgery after an average of 9 years after fusion. No patient with atlantoaxial fusion developed superior migration of the odontoid. Subaxial subluxation requiring surgery developed early in patients after occipitocervical fusion. This was not true of atlantoaxial fusion. Early atlantoaxial fusion seemed to prevent the development of superior migration of the odontoid. When occipitocervical fusion is necessary and early subaxial subluxation is present, longer fusions or occipitocervicothoracic fusion should be strongly considered.

Adult↗
PubMed1991

Multiple glomangiomas of lower limb.

A young man with multiple painful nodules on the left lower limb is presented. Histology of one of the nodules proved the diagnosis of glomangioma.

Adult↗
PubMed1990

Expression of 11 beta-hydroxysteroid dehydrogenase using recombinant vaccinia virus.

Ligand specificity of the type I steroid receptor is apparently conferred by the activity of 11 beta-hydroxysteroid dehydrogenase. To determine the kinetic properties of this enzyme, rat liver cDNA was expressed in cultured cells using recombinant vaccinia virus. Although this enzyme catalyzes only dehydrogenation when purified from rat liver, the recombinant enzyme obtained from cell lysates catalyzed both 11 beta-dehydrogenation of corticosterone to 11-dehydrocorticosterone and the reverse 11-oxoreduction reaction. At pH 8.5, the first order rate constant Kcat/Km for dehydrogenase activity exceeded that for reductase (63 vs. 38 min-1 x 10(-4], whereas the rate constants for the two reactions were nearly equal (48 vs. 47 min-1 x 10(-4] at pH 7.0. These results are consistent with the previously determined pH optima for these activities in liver microsomes. Removal (with glucose-6-phosphate dehydrogenase) of NADP+ produced by the reductase reaction significantly increased reductase activity. Glycyrrhetinic acid, a known inhibitor of the dehydrogenase reaction, also inhibited the reductase reaction at slightly higher concentrations (50% inhibitory concentration, less than 5 nM for dehydrogenase, 10-20 nM for reductase). Partial inhibition of glycosylation with A1-tunicamycin decreased dehydrogenase activity 50% without affecting reductase activity. The data demonstrate that a single polypeptide catalyzes both dehydrogenation and reduction, although the presence of additional enzyme forms catalyzing one or the other activity has not been ruled out.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1990

Acute neurobehavioural toxicity of phosphamindon and its drug-induced alteration.

Phosphamidon, a systemic organophosphate insecticide, (1.4 mg/kg - dose 1/4th of LD50 given ip), produced several autonomic, neurological and behavioral effects in mice with peak effects being at 15 min. Similar dose in rats also abolished conditioned avoidance response. Pre-treatment with atropine, iproniazid, alpha-methyl-p-tyrosine, p-chlorophenylalanine or thiosemicarbazide reduce many of these effects. This suggests that phosphamidon toxicity involves the central cholinergic, adrenergic, serotonergic and GABAergic systems in addition to peripheral cholinergic effects.

Animals↗
PubMed1990

Effect of subacute insecticide exposure on body weight, drug responses & electrical convulsions in mice.

Effect of subacute insecticide exposure was studied in male albino mice treated with phosphamidon, propoxur or aldrin at 1/40 LD50 dose intraperitoneally daily for 8 wk. The parameters studies included body weight, pentobarbitone (50 mg/kg) sleeping time, chlorpromazine (6 mg/kg) induced motor incoordination and convulsions induced by leptazol (100 mg/kg) and electrical stimulation (18 mA for 0.2 msec). While body weight and electrically induced convulsions were not affected, the effect of various drugs was significantly decreased. The observed changes may be due to the induction of hepatic drug metabolising enzymes by the insecticides. The study suggests that certain dose adjustment of drugs may be necessary in those exposed to insecticides over long periods.

Animals↗
PubMed1990

Role of cimetidine in prevention and treatment of stress induced gastric bleeding in neonates.

Gastric bleeding from stress ulcers in acutely sick infants frequently signals impending mortality. This study was carried out to evaluate the efficacy of cimetidine in preventing and treating stress ulcers in such neonates. One hundred babies were included in this study. Out of this, 32 babies were given prophylactic cimetidine and 68 neonates acted as controls. It was observed that the babies on prophylactic cimetidine fared better than controls. In the second part of study, 77 neonates with clinical evidence of hemorrhage were included, 43 were put on cimetidine and 34 acted as controls. It was observed that babies on cimetidine therapy showed a better response. The gastric bleeding stopped earlier, and more babies responded favourably to this therapy. Use of cimetidine in stress induced bleeding in high risk neonates is recommended.

Cimetidine↗
PubMed1990

Effect of subacute DDT on pharmacokinetics of isoniazid and liver function in rabbits.

DDT administration (30 mg/kg per day, po, for 21 consecutive days) to rabbits showed an increase in peak plasma concentration and a decrease in time to reach peak plasma concentration of isoniazid whereas no change was observed in elimination rate constant and area under the plasma concentration-time curve. DDT treatment caused increased absorption of isoniazid. Early signs of hepatic damage were also observed. Since there was no change in the levels of serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase, it can be concluded that DDT does not significantly affect liver function at the dosage used. The observed elevated levels of alkaline phosphatase could be due to direct activation of the enzyme. Leukopaenia and neutropaenia with relative lymphocytosis indicated that DDT might have suppressant effect on granulocyte cell line of WBCs.

Animals↗
PubMed1990

Effect of electroconvulsions on leucocyte counts.

Acute electroconvulsions (EC) induced polymorphonuclear leucocytosis with relative lymphopenia in rabbits. On daily EC challenge there was no tolerance to this response but the response was blocked by propranolol. Repeated daily administration of exogenous adrenaline or EC challenge increased basal total leucocyte and polymorph but decreased the lymphocyte counts. It is suggested that repeated exposure to exogenous adrenaline or endogenous adrenaline (through EC) somehow sensitizes the system responsible for the release of polymorphs from the bone marrow.

Animals↗
PubMed1989

Evaluation of the binding to fixed platelets of agonists and antagonists of ADP-induced aggregation.

Steady state binding of eleven different ADP analogues to formaldehyde-fixed platelets has been determined in a competitive binding assay using 3H-ADP. The compounds tested were the inactive analogues L-ADP and L-ATP; the agonists 2-chloroadenosine 5'-diphosphate, adenosine 5'-O-(2-thiodiphosphate) and the diasteroisomeric pair Sp-adenosine 5'-(1-thiodiphosphate) (Sp-ADP-alpha-S) and Rp-adenosine 5'-(1-thiodiphosphate) (Rp-ADP-alpha-S); and the antagonists adenosine 5'-O-thiomonophosphate, 2-chloroadenosine 5'-O-thiomonophosphate, 2-choloroadenosine 5'-triphosphate, and the diastereoisomeric pair 5'-(1-thiotriphosphate) (Sp-ATP-alpha-S) and RP-adenosine 5'-(1-thiotriphosphate) (Rp-ATP-alpha-S). All compounds tested competed at the high affinity binding sites for ADP previously identified (Blood 1988; 71: 110-6) but in some cases competition could not be demonstrated at the low affinity sites because of the high nucleotide concentrations required. As a group, C2-substituted analogues bound less strongly (Ki greater than 2 micro M) than did the analogues without substituents in the purine ring (Ki less than 0.7 microM). With the pair of diastereoisomeric agonists Sp-ADP-alpha-S and Rp-ADP-alpha-S the Ki values at the high affinity site (210 nM and 560 nM) were of the same relative magnitude and in the same direction as their reported potencies as agonists (Ki 4 microM and 20 microM). With the diastereoisomeric antagonists Sp-ATP-alpha-S and Rp-ATP-alpha-S a similar relationship was seen between affinity (17 nM and 156 nM) and inhibitory potency (Ki 4 microM and 20 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1989

Cloning and expression of rat cDNA encoding corticosteroid 11 beta-dehydrogenase.

Corticosteroid 11 beta-dehydrogenase (11-DH) catalyzes the conversion of cortisol to the inactive metabolite cortisone. Absence of 11-DH activity leads to a potentially fatal form of childhood hypertension termed apparent mineralocorticoid excess. As a first step in elucidating the molecular basis of this disorder, we isolated and characterized a rat cDNA clone encoding 11-DH. This clone hybridized to a single mRNA species in liver, kidney, and testis RNA but not to RNA from heart. The insert was 1265 base pairs long and included an 861-base pair open reading frame encoding 287 amino acids. A search of sequence databases revealed that 11-DH is identical in about 27% of amino acid residues to ribitol dehydrogenase from Klebsiella and to the product of the nodG gene from the nitrogen-fixing bacterium, Rhizobium meliloti, thus defining a new superfamily of genes encoding dehydrogenases. The 11-DH cDNA was expressed by transfection into Chinese hamster ovary cells under the control of an SV40 promoter. The expressed enzyme mediated both 11 beta-dehydrogenation and the reverse 11-oxoreduction reaction. Southern blot analysis of rat and human DNA suggested that additional genes related to 11-DH exist in both species.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1989

Centchroman--a non-steroidal anti-cancer agent for advanced breast cancer: phase-II study.

Treatment with Centchroman (3,4-trans-2,2-dimethyl-3-phenyl-4-p-(beta-pyrrolidinoethoxy) phenyl-7-methoxy chroman) has been evaluated in 4 male and 75 female patients with advanced breast cancer. The overall response rate, including both male and female cases, was 40.5%. Among the female patients, the overall response rate was 38.7%. The median duration of response was 6 months. One of the 4 male patients showed a complete response and 2 showed partial responses. The responses were more marked for bone, pulmonary, soft tissue, skin and lymph-node metastases than for liver metastases.

Adult↗