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Biomedical subjects

A Kumar

Publications and source records attributed to A Kumar.

At least 1,765 records · Page 98Linked to original sources

Expression of human angiotensinogen cDNA in Escherichia coli.

Human angiotensinogen cDNA clones were isolated from a human liver library. Nucleotide sequence analysis of these cDNA clones revealed that position 1075 in the messenger RNA, which is part of a PstI recognition sequence, is different from the published sequence (Kageyama, R., Ohkubo, H., and Nakanishi, S. (1984) Biochemistry 23, 3603-3609). This change results in an altered amino acid at this position in the corresponding protein sequence and suggests possible restriction fragment length polymorphism. The full length human angiotensinogen cDNA was constructed from partial cDNA clones and ligated into an isopropyl-1-thio-beta-D-galactopyranoside inducible bacterial expression vector pUC9 to develop expression plasmid pUCHAG27. This plasmid permitted the synthesis of human angiotensinogen in Escherichia coli. The recombinant bacteria overproduced a 53-kDa protein which was recognized by anti-human angiotensinogen antibodies. The synthesis of this protein was greatly increased upon induction with isopropyl-1-thio-beta-D-galactopyranoside. The chimeric protein, almost identical to human angiotensinogen, was partially purified by ammonium sulfate fractionation and gel filtration on Sephadex G-100. Human kidney renin was shown to enzymatically cleave this recombinant protein to produce des-(angiotensin I)-angiotensinogen and a small polypeptide. Thus, we provide evidence that recombinant human angiotensinogen synthesized through E. coli is biologically active and serves as a substrate for human renin.

Amino Acid Sequence↗

Tissue specific hormonal regulation of the rat angiotensinogen gene expression.

Angiotensinogen is the precursor of the most potent pressor substance, angiotensin. Angiotensinogen levels are increased in some forms of human hypertension. Its levels are modulated by various factors including glucocorticoids, estrogens, and prostaglandins. We have recently reported the isolation of a human angiotensinogen cDNA clone and provided evidence for the presence of its mRNA in rat liver, brain, and heart. In this communication we report the effect of dexamethasone and estradiol on angiotensinogen mRNA levels in rat liver, brain, and heart. Our results indicate that angiotensinogen levels are increased to different extents in these three tissues as a result of glucocorticoid or estrogen administration.

Angiotensinogen↗

Evidence for negative regulation of T cell growth by low affinity interleukin 2 receptors.

Two experimental situations have been studied, and the results provide evidence for a negative regulatory role for the low affinity interleukin 2 receptor (LA-IL 2R). The IL 2-dependent T helper cell line L-14, deprived of IL 2, becomes quiescent and expresses comparable numbers of high affinity IL 2R (HA-IL 2R) and LA-IL 2R. After activation by recombinant IL 2, this cell line preferentially expresses LA-IL 2R. The IL 2 responsiveness of the L-14 cell line was found to vary according to the ratio of LA-IL 2R to HA-IL 2R: the relative predominance of the LA-IL 2R coincides with a hyporeactivity of cells to IL 2. In contrast, a predominance of HA-IL 2R is accompanied by an increase in cellular IL 2 reactivity. Treatment of three IL 2-dependent T cell lines (L-14, HT-2, and C30.1) with limited amounts of recombinant IL 2 and moderate concentrations of anti-IL 2R monoclonal antibodies stimulates T cell growth. This treatment was shown to selectively diminish the expression of membrane LA-IL 2R. The stimulation was attributed to the decrease of expression of LA-IL 2R.

Animals↗

Albumin lung/heart ratio change. A simple clinical means of documenting increased pulmonary endothelial permeability to protein.

We investigated a simple method that can be used at the bedside for documenting the net accumulation of albumin in the lung. The technique employs measurement with a computer-linked gamma camera of the activity ratio in an area of the right lung compared with the same-sized area in the heart at 20 minutes and three hours following intravenous injection of technetium Tc 99m albumin. We applied this measurement to three groups of patients: a control group and patients with roentgenographic evidence of edema classified according to clinically available criteria as either hydrostatic edema or permeability edema to see if we could document differences among these groups. In control patients this ratio did not increase by more than seven units between the 20-minute and three-hour measurements. Of 18 patients classified by other routine clinical means as having hydrostatic pulmonary edema, 89% showed no increase in lung albumin accumulation. In 29 patients with permeability edema associated with the so-called adult respiratory distress syndrome, 31% showed evidence of net pulmonary albumin accumulation. These findings suggest that some patients otherwise classified as having hydrostatic edema have concomitant permeability changes in the microvasculature and that permeability edema represents a spectrum of endothelial damage.

Capillary Permeability↗

Preoperative chemotherapy for fungating breast cancer.

Thirty cases of fungating breast cancer (stages III and IV) were treated preoperatively by combination chemotherapy using cyclophosphamide (Endoxan), methotrexate, 5-fluorouracil, and prednisone. Mastectomy was performed after 2 cycles of preoperative chemotherapy followed by 6 more cycles postoperatively. Of 30 patients, 25 (83.3%) were made operable and had better disease-free survival. Preoperative chemotherapy has an advantage as regards improvement in quality and longevity without much toxicity, and provides a better palliation.

Breast Neoplasms↗

Pseudoaneurysm of anomalous right hepatic artery as a cause for hemosuccus pancreatitis.

A pseudoaneurysm from the right hepatic artery was associated with chronic pancreatitis in an elderly patient with recurrent episodes of bleeding into the pancreas. Preoperative ultrasonography and enhanced computed tomographic scan revealed the nature of lesion but angiography was required to demonstrate the causative right hepatic artery, which was anomalous.

Aneurysm↗

Enhancement of anti-sheep erythrocyte plaque-forming cell levels by cimetidine in vivo.

Previous studies demonstrated an immunomodulatory role for cimetidine in contact sensitivity responses in vivo. The present experiments have examined the effects of cimetidine upon in vivo antibody production. When given intravenously, cimetidine treatment consistently resulted in enhanced numbers of IgM plaque-forming cells (PFC) following immunization with sheep erythrocytes. This enhancement was dependent upon both the dose and timing of cimetidine administration. In timing experiments, maximal enhancement of PFC levels was obtained when cimetidine was given at the time of or within three days following immunization. Treatment with cimetidine four days after immunization or one day before assay led to a slight decline in PFC level. In contrast, intraperitoneal treatment with cimetidine has little effect upon the anti-sheep erythrocyte PFC level regardless of dose or timing. Overall, these results indicate that cimetidine may be capable of modulating PFC development in vivo. This modulation, however, depends critically upon dose, timing, and route of cimetidine administration.

Animals↗

Induction of the ceruloplasmin mRNA in Balb/C 3T3 cells after Rous-Sarcoma virus transfection.

Ceruloplasmin is a copper containing serum glycoprotein. It is an acute-phase protein and its levels are increased in inflammation and in a number of experimental and human tumors. It is normally synthesized in the liver and not in fibroblasts. In this paper we present evidence that ceruloplasmin mRNA is synthesized in Balb/C 3T3 cells and its levels are increased about 3-fold in Rous-Sarcoma virus (RSV) transformed cells. The ceruloplasmin mRNAs from rat liver and RSV 3T3 cells have the same electrophoretic mobility.

Animals↗

Hematological indices in copper-poisoned rats.

The effects of 30 days oral administration of a sublethal daily dose (0.1 g/kg body weight) of copper sulfate on the blood constituents of albino rats were studied. Percent hemoglobin, number of red blood corpuscles, plasma corpuscular volume and mean corpuscular volume were decreased significantly. No marked alteration was observed in the number of white blood corpuscles, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and alkaline phosphatase activity. The concentrations of blood glucose, cholesterol, bilirubin and urea were elevated in the copper-fed rats. The activities of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and lactate and glutamate dehydrogenases were increased significantly, but blood total protein and acid phosphatase activity were reduced.

Animals↗

Incomplete epispadiac urethral duplication with dorsal penile curvature.

Incomplete urethral duplication, although not uncommon, usually is associated with insignificant chordee of the penis and it is clinically asymptomatic. We report a case of incomplete urethral duplication with marked dorsal curvature of the penis and other congenital anomalies. Excision of wedge-shaped ellipses of the tunica albuginea from the ventral aspect of the corpus provided an excellent result.

Adolescent↗

Vesicovaginal fistulas of uncommon etiology.

We report 2 cases of vesicovaginal fistulas sustained during sexual intercourse. In our first case fistula formation was probably the result of physical disparity of the partners and a frightened, unprepared woman. In the second case increased friability caused by hormonal influence during menstruation and a urinary infection probably contributed to fistula formation. Both patients underwent a successful, transabdominal repair with omental interposition.

Adult↗

Synthesis of 5-chloro-5,8-dideaza analogues of folic acid and aminopterin targeted for colon adenocarcinoma.

Several classical quinazoline analogues of folic acid bearing chloro or methyl substituents at position 5 were evaluated as inhibitors of the growth of four human gastrointestinal adenocarcinoma cell lines in vitro. The preparation of two of these, 5-chloro-5,8-dideazaisofolic acid, 1e, and 5-chloro-5,8-dideazaisoaminopterin, 2a, is reported for the first time. In addition, a new synthetic route to 5-chloro-5,8-dideazaaminopterin, 2b, is described. For compounds having a 2,4-diamino configuration, the presence of chlorine at position 5 afforded superior growth inhibitory potency. However, compound 1e was substantially less effective than its 5-methyl counterpart.

Adenocarcinoma↗