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Biomedical subjects

R Dhar

Publications and source records attributed to R Dhar.

At least 55 records · Page 3Linked to original sources

Unusual non-serogroup O1 Vibrio cholerae bacteremia associated with liver disease.

A 50-year-old woman and a 31-year-old man with underlying liver disease presented with fever and signs of liver failure. The blood cultures in both cases yielded non-serogroup O1 Vibrio cholerae strains which were biochemically identical except that one strain was nonmotile. Despite treatment with antibiotics, the older patient died; the other patient survived. Both strains were found to be susceptible to most antibiotics tested in vitro. No apparent source of infection could be identified in either case.

Adult↗

Cimetidine-induced galactorrhea.

Various breast abnormalities have been described in patients treated chronically with cimetidine, but galactorrhea has been reported only twice in the medical literature. In both cases, there appeared to be an associated hyperprolactinemia. These problems could well represent a consequence of histamine2-receptor blockade. We report here a female patient with hepatic cirrhosis and portal hypertension who developed hyperprolactinemia and galactorrhea while on long-term cimetidine therapy. Both the hyperprolactinemia and the galactorrhea disappeared when the patient was switched to ranitidine, an alternative H2-receptor blocker. A review of the previous case reports and relevant literature is included.

Cimetidine↗

cDNA cloning of porcine transforming growth factor-beta 1 mRNAs. Evidence for alternate splicing and polyadenylation.

Most eukaryotic cells encode principally a 2.5-kilobase (kb) transforming growth factor (TGF)-beta 1 mRNA. However, we have found two major TGF-beta 1 RNA species, 3.5 and 2.5 kb long, in porcine tissues. The 3.5-kb species has a longer 3'-untranslated sequence generated by the selection of an alternate polyadenylation site. There is a 117-nucleotide sequence within this unique 3' region, which is similar to the PRE-1 repetitive sequence of unknown function, reported earlier in the porcine genome. We have also cloned and characterized an alternately spliced mRNA species specific for the TGF-beta 1 gene, in which exons IV and V of the corresponding human TGF-beta 1 gene are deleted. The nucleotide sequence of this cDNA clone predicts a putative precursor protein of 256 amino acids; the N-terminal 211 amino acids of this putative protein are identical to the TGF-beta 1 precursor protein (exons I, II, and III of the human TGF-beta 1 gene), but the C-terminal 45 amino acids are distinct, due to a frameshift in the translation of exons VI and VII. In addition we provide data for the existence of other mRNA species generated in a tissue-specific manner either by alternate splicing or by heterogeneous 5' leader sequences.

Amino Acid Sequence↗

Accumulation of processing intermediates of the RAS2 protein in strain 112 of Saccharomyces cerevisiae.

Strain 112 (RAS1 RAS2) contains a naturally occurring mutation which significantly retards processing of the RAS2 gene product. This mutation, resulting in the accumulation of precursor forms of RAS2 protein, has been assigned by genetic analysis to a single chromosomal locus distinct from the RAS2 locus. In addition to the known precursor molecule of 41000 daltons (p41), 112 cells accumulate within the soluble fraction an intermediate form of RAS2 (p40-1), which migrates, in SDS-polyacrylamide gel, between p41 and the fully processed, membrane-bound 40,000 daltons (p40) product. We propose for RAS2 protein processing the following sequence of events: p41 greater than p40-1 greater than p40 where p40-1 represents a RAS2 intermediate required for the targeting of the protein to the plasma membrane.

Electrophoresis, Polyacrylamide Gel↗

Multiple regulatory mechanisms control the expression of the RAS1 and RAS2 genes of Saccharomyces cerevisiae.

Expression of the RAS1 and RAS2 genes of Saccharomyces cerevisiae has been examined at the transcriptional and translational levels. When dextrose is the carbon source, the steady-state amount of RAS1 mRNA and the rate of RAS1 protein synthesis are reduced in parallel as cells approach the mid-exponential phase of growth. RAS1 mRNA levels and protein synthesis are very low at all stages of growth when ethanol rather than dextrose is provided as the sole carbon source. The rate of RAS2 protein synthesis is regulated differently. In cells cultured on dextrose, it is lowest in the early exponential phase, increases approximately 10-fold and remains nearly constant as cells approach stationary phase. By contrast, RAS2 mRNA is found at uniformly high levels at all phases of exponential growth, suggesting that the translational efficiency of RAS2 mRNA is repressed during the early exponential phase. This repression is not observed when ethanol is the sole carbon source. Nutrient starvation, resulting in G1 arrest and sporulation in diploids, leads to greatly decreased amounts of RAS2 mRNA, accomplished in part by selective repression of RAS2 transcripts with particular 5' ends. However, this reduction in RAS2 mRNA levels has little effect on the rate of RAS2 protein synthesis, suggesting that the translational efficiency of RAS2 mRNA is stimulated by nutrient starvation. The combination of transcriptional and translational controls which regulate yeast RAS gene expression seems to ensure that one or the other RAS proteins will be produced over a wide range of physiological states.

Cell Cycle↗

A modified indirect fluorescent antibody test for the diagnosis of brucellosis.

We adapted the conventional indirect fluorescent antibody (IFA) test to assay IgM and IgG Brucella-specific antibodies to differentiate acute from chronic infections rather than measure total antihuman globulin specific antibodies. The results were compared with the slide agglutination test (SAT) used for screening and the quantitative microagglutination test (MAT). Of a total of 118 randomly selected samples sent for anti-Brucella antibodies received at a general hospital laboratory, 58 (47.9%) were found to be positive for IFA-IgG test but not necessarily by other tests. Eleven of these cases were positive for Brucella melitensis by culture. Sixty serum samples found negative for Brucella antibodies by IFA and other tests were of patients with medical conditions other than brucellosis. Fifty serum samples from healthy blood donors were negative for Brucella spp. antibodies by all the three tests. The IFA test was found to be a more sensitive test than MAT and distinguished an acute infection from chronic disease.

Acute Disease↗

Recurrent epidermal cyst infection caused by Brucella melitensis in a diabetic patient.

A presternal swelling diagnosed clinically as a sebaceous cyst in a 60-year-old diabetic patient was surgically drained, and the aspirated purulant material yielded growth of Brucella melitensis. The swelling recurred four times and was drained on every occasion. The patient responded to surgical excision and antibrucella treatment. The histologic diagnosis was an epidermal cyst.

Brucellosis↗

Comparative study of culture, direct immunofluorescent antibody test and enzyme immunoassay for the diagnosis of urogenital infections caused by Chlamydia trachomatis.

We studied three population groups (161 symptomatic female, 62 asymptomatic female and 74 symptomatic male) to determine the prevalence of genital tract infections caused by Chlamydia trachomatis in Kuwait. Three techniques, viz. tissue culture, direct immunofluorescent antibody test (MicroTrak) and enzyme immunoassay (Chlamydiazyme) were employed for the detection of C. trachomatis. The overall positivity based on positive tissue culture in symptomatic cases was 16.2% (17.4% in female and 13.5% in male). The two rapid methods for antigen detection were compared with tissue culture. Based on a positivity criterion of greater than 10 elementary bodies in the direct immunofluorescent antibody assay, sensitivity and specificity of the test were 66.7% and 97.2% while the positive and negative predictive values were 77.8% and 97.2% respectively. The sensitivity and specificity of the enzyme immunoassay were 61.3% and 96.7% with positive and negative predictive values of 80.8% and 94.6% respectively. There was an agreement of 92.0% between the three tests. The two rapid antigen detection tests seem to be similar and provide an alternative for diagnosing Chlamydia trachomatis in our patients.

Cells, Cultured↗

Clinical features, evaluation, and detection of colorectal cancer.

The most common presentation of colorectal carcinoma is in the symptomatic patient, most often with complaints of rectal bleeding, abdominal pain, or change in bowel habits. Symptomatic patients often have advanced disease and, because surgical resection is the only effective therapy at present, their chance for cure is poor. Until effective treatment is available, therefore, we must identify patients at high risk for lifelong screening. In addition, more effective means of surveillance of the general population need to be developed in order to diagnose patients at risk for sporadic colorectal cancer, given that this represents the majority of patients with disease. Tumor markers also would be useful to find residual disease while it is still resectable in patients who have undergone surgery for curative resection.

Colorectal Neoplasms↗

Differential regulation of c-Ha-ras and c-Ki-ras gene expression in rat mammary gland.

Steady-state levels of c-Has-ras and c-Ki-ras RNA in gestating and lactating rat mammary gland were measured. The c-Ha-ras-specific RNA level increased during gestation and declined with the onset of lactation. On the contrary, the level of c-Ki-ras RNA remained unchanged both during gestation and lactation. There was no change in the level of ras-transcripts in either growing or regressing 7,12-dimethylbenz[a]anthracene-induced mammary tumors. Intravenous infusion of prolactin or implantation of pituitary-derived tumor, which secretes mammotropic hormone, in virgin female rats resulted in decreased levels of c-Ha-ras RNA and no change in c-Ki-ras RNA levels. Our results suggest the transcription of c-Ha-ras and c-Ki-ras genes is differentially regulated.

9,10-Dimethyl-1,2-benzanthracene↗

Carbon source regulation of RAS1 expression in Saccharomyces cerevisiae and the phenotypes of ras2- cells.

Transcriptional analysis of the yeast RAS genes in different culture conditions suggests that the inability of ras2 mutants to grow in nonfermentable carbon sources results from the regulation of RAS1 mRNA expression. The amount of RAS1 mRNA is significantly repressed in cultures grown on the nonfermentable carbon sources ethanol and acetate. As a result, low RAS function should be expressed under these conditions in a ras2 mutant. This can explain the inability of ras2- cells to grow on nonfermentable carbon sources. This interpretation is supported by the finding that an extragenic suppressor of ras2- (sra6-15), which restores growth on ethanol or acetate, also leads to an increase in the amount of RAS1 mRNA under these conditions. The sra6-15 mutation does not alter the level of RAS1 mRNA in cells grown on glucose. The pattern of transcriptional regulation described for the RAS1 gene is not shared by RAS2, indicating differential control of the functionally homologous yeast RAS genes at the level of gene expression.

Carbon↗

Nucleotide sequence of the two rat cellular rasH genes.

We present the nucleotide sequence of the coding region of the rat c-rasH-1 gene and a partial sequence analysis of the rat c-rasH-2 gene. By comparing these sequences with the Harvey murine sarcoma virus ras gene, we predict that the p21 protein encoded by the Harvey virus differs from the cellular c-rasH-1-encoded p21 at only two amino acids; those at positions 12 and 59. Alterations at each of these positions may play a role in activating the viral p21 protein. The c-rasH-2 gene is likely to be a nonfunctional pseudogene because it lacks introns, cannot be activated to transform NIH 3T3 cells, and differs in sequence from both c-rasH-1 and v-rasH at several base pair positions.

Amino Acid Sequence↗

Nucleotide sequence of two rasH related-genes isolated from the yeast Saccharomyces cerevisiae.

A complete nucleotide sequence of two ras-related yeast genes (c- rassc -1 and c- rassc -2) isolated from the yeast strain Saccharomyces cerevisiae is reported. They encode predicted polypeptides of 40,000 and 41,000 daltons, respectively. The N-terminal 170 amino acids from both genes show extensive amino acid homology to other ras genes from vertebrates, whereas their C-termini have diverged. These genes should be useful in the elucidation of a normal biological function of ras-related genes in a simple system like yeast.

Amino Acid Sequence↗

The human c-ras1H oncogene: a mutation in normal and neoplastic tissue from the same patient.

The c-ras1H oncogene can be distinguished from its normal cellular counterpart by the loss of a restriction endonuclease site. This sequence alteration is the basis of a rapid screening method for the presence of this oncogene. DNA's from 34 individuals were screened by this method, and all were homozygous for the normal allele. In contrast, DNA from a patient's bladder tumor, as well as DNA from his normal bladder and leukocytes, were heterozygous at that restriction endonuclease site. Further restriction enzyme mapping pinpointed the change in the mutant allele as being one of two nucleotides, either of which would change the 12th amino acid (glycine) in the normal c-ras1H gene product. Point mutations in the codon for this amino acid have previously been described in a bladder tumor cell line and in the viral oncogene v-rasH. These results indicate that the patient carried a c-ras1H oncogene in his germ line, raising the possibility that the c-ras1H oncogene confers a predisposition to neoplasia.

Base Sequence↗