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Biomedical subjects

Y Haraguchi

Publications and source records attributed to Y Haraguchi.

At least 91 records · Page 5Linked to original sources

Human liver-type arginase gene: structure of the gene and analysis of the promoter region.

The gene for human liver-type arginase (EC 3.5.3.1), a urea cycle enzyme, was cloned and the structure was determined. This gene is 11.5 kilobases long and is split into 8 exons. The cap site was determined by nuclease S1 mapping and primer extension. A "TATA box"-like sequence is located 28 bases upstream from the cap site, and a sequence similar to the binding sites of the transcription factor CTF/NF1, a "CAAT box"-binding protein, is located 72 bases upstream. In the 5' end region, sequences resembling the glucocorticoid responsive elements, the cAMP responsive elements, and the enhancer core sequences are present. The immediately 5' flanking region of the human gene up to position -105 is 84% identical with the corresponding segment of the rat gene. In this region of the human gene, one DNase I-protected area and several hypersensitive cleavage sites were detected by footprint analysis, using nuclear extracts from the rat liver. The protected area contains the sequence similar to the binding sites of CTF/NF1 and also overlaps with the sequence resembling the glucocorticoid responsive elements.

Amino Acid Sequence↗

Plasma GRP-like immunoreactivity in healthy and diseased subjects.

Gastrin releasing peptide(GRP)-like immunoreactivity in human plasma was measured using radioimmunoassay of neuromedin C (NMC) in 83 healthy and 58 diseased subjects. In the healthy group, the mean value of fasting GRP-like immunoreactivity was 2.1 +/- 1.4 (mean +/- SD) pmol/L. There was a slight positive correlation between the GRP-like immunoreactivity values and aging. Postprandial serial measurements demonstrated that GRP-like immunoreactivity showed no response to a significant elevation of serum gastrin concentration. The group with chronic renal failure on hemodialysis gave the highest value, 7.1 +/- 2.1 pmol/L (p less than 0.01). There were no statistical differences between the healthy controls and groups with peptic ulcer, liver cirrhosis, diabetes mellitus or carcinomas, although some cancer patients had a marked increase in GRP-like immunoreactivity value.

Adult↗

Evidence of correlation between 50-kilobase plasmid of Salmonella choleraesuis and its virulence.

A plasmid of 50 kilobases (kb) was found in all six strains of Salmonella choleraesuis studied, originally isolated from septicemic swine or man. A derivative cured of the 50 kb plasmid was isolated after treatment with novobiocin, and its virulence compared to that of the parent by intraperitoneal injection into mice. The lethality of the parent strain was found higher than that of the cured strain. With a sublethal number of cells of the parent strain injected, the spleen, liver and lymph nodes in various sites were markedly enlarged, and the bacteria were isolated from the heart blood. In contrast to this, neither enlargement of the organs nor recovery of organisms was observed with the cured strain. The Tn1-tagged 50 kb plasmid was next introduced by transformation into the cured strain. The virulence of the plasmid-reintroduced strain was higher than that of the cured strain, and in fact identical to that of the parent. We conclude that the 50 kb plasmid of S. choleraesuis is closely related with the mouse virulence of the organism.

Animals↗

A case of generalized juvenile gastrointestinal polyposis associated with gastric carcinoma.

A case of generalized juvenile gastrointestinal polyposis associated with gastric adenocarcinoma is described. A 31-year-old male patient developed polyposis of the stomach complicated by gastric carcinoma and multiple polyps in the colon. Polyps of the stomach and colon were pathologically consistent with juvenile polyp, but adenomatous changes were also present in a very small percentage of the juvenile polyps. This case strongly suggests the possibility of carcinoma developing in patients with generalized juvenile gastrointestinal polyposis.

Adenocarcinoma↗

Immunocytochemical localization of ornithine transcarbamylase in rat intestinal mucosa. Light and electron microscopic study.

We investigated light and electron microscopic localization of ornithine transcarbamylase (OTC) in rat intestinal mucosa. In the immunoblotting assay of OTC-related protein, a single protein band with a molecular weight of about 36,500 is observed in extracts of liver and small intestinal mucosa but is not observed in those of stomach and large intestine. For light microscopy, tissue slices of the digestive system were embedded in Epon and stained by using anti-bovine OTC rabbit IgG and the immunoenzyme technique. For electron microscopy, slices of these and the liver tissues were embedded in Lowicryl K4M and stained by the protein A-gold technique. By light microscopy, the absorptive epithelial cells of duodenum, jejunum, and ileum stained positively for OTC, but stomach, large intestine, rectum, and propria mucosa of small intestine were not stained. Electron microscopy showed that gold particles representing the antigenic sites for OTC were confined to the mitochondrial matrix of hepatocytes and small intestinal epithelial cells. However, the enzyme was detected in mitochondria of neither liver endothelial cells, submucosal cells of small intestine, nor large intestinal epithelial cells. Labeling density of mitochondria in the absorptive epithelial cells of duodenum, jejunum, and ileum was about half of that in liver cells.

Animals↗

Further studies on the hydrolysis of salicyluric acid in intestinal microorganisms and prolonged blood concentration of salicylic acid following rectal administration of salicyluric acid in rabbits.

The blood concentrations of salicyluric acid and salicylic acid following intracecal and rectal administration of salicyluric acid were determined in rabbits. Immediate and very extensive salicylic acid formation in the cecum was found following intracecal administration. After rectal administration, a small amount of salicyluric acid was absorbed in intact form. The rest was rapidly hydrolyzed to salicylic acid, which was subsequently absorbed. The blood concentration of salicylic acid was maintained at 1.3-1.8 micrograms/ml from 2 to 12 h. Three doses of salicyluric acid were administered rectally. The peak level of salicyluric acid increased with dose. However, salicylic acid concentration in the blood following administration of salicyluric acid at 10.0 mg/kg (salicylic acid equivalent) was not double that observed following administration of salicyluric acid at 5.0 mg/kg (salicylic acid equivalent). It appears that a larger amount of salicyluric acid in the rectal lumen may have saturated the glycine deconjugation system.

Administration, Rectal↗

Immunological and clinical effects of interferon-gamma on Crohn's disease.

Five patients with Crohn's disease (CD) confined to the small intestine were studied to determine whether intravenous administration of interferon (IFN)-gamma to normalize immunological imbalance produces clinical improvement. A daily dose of 12 million IU of IFN-gamma was intravenously infused for four weeks. Laboratory data, immunological responses, clinical and radiologic findings were evaluated after administration. Laboratory data showed no significant change after treatment. Immunological studies also failed to demonstrate any significant change except for a significant increase of natural killer (NK) cell activity after IFN-gamma infusion. Clinical assessment by Crohn's disease activity index as well as radiologic findings disclosed no definite improvement. This study suggests that enhancement of NK cell activity or augmentation of immunological imbalance induced by IFN-gamma does not play an important role in the pathogenesis of CD.

Adult↗

Molecular cloning and nucleotide sequence of cDNA for human liver arginase.

Arginase (EC 3.5.3.1) catalyzes the last step of the urea cycle in the liver of ureotelic animals. Inherited deficiency of the enzyme results in argininemia, an autosomal recessive disorder characterized by hyperammonemia. To facilitate investigation of the enzyme and gene structures and to elucidate the nature of the mutation in argininemia, we isolated cDNA clones for human liver arginase. Oligo(dT)-primed and random primer human liver cDNA libraries in lambda gt11 were screened using isolated rat arginase cDNA as a probe. Two of the positive clones, designated lambda hARG6 and lambda hARG109, contained an overlapping cDNA sequence with an open reading frame encoding a polypeptide of 322 amino acid residues (predicted Mr, 34,732), a 5'-untranslated sequence of 56 base pairs, a 3'-untranslated sequence of 423 base pairs, and a poly(A) segment. Arginase activity was detected in Escherichia coli cells transformed with the plasmid carrying lambda hARG6 cDNA insert. RNA gel blot analysis of human liver RNA showed a single mRNA of 1.6 kilobases. The predicted amino acid sequence of human liver arginase is 87% and 41% identical with those of the rat liver and yeast enzymes, respectively. There are several highly conserved segments among the human, rat, and yeast enzymes.

Amino Acid Sequence↗

Technetium-99m serum albumin measurement of gastrointestinal protein loss in a subtotal gastrectomy patient with giant hypertrophic gastritis.

Gastrointestinal protein loss was measured using Tc-99m labeled human serum albumin in a patient with giant hypertrophic gastritis. Gastric secretion was aspirated via a nasogastric tube and measured for radioactivity after intravenous injection of Tc-99m albumin. Assessment of radioactivity of the collected gastric secretion yielded a total radiocount of 98.7 kilocounts per minute within 6 hours, which is equivalent to 1.1% of the total dose. Therefore, at least 1.1% of the circulating albumin was excreted into the gastric cavity within 6 hours, and, since simultaneous abdominal imaging did not demonstrate obvious accumulation of tracer in the gastrointestinal tract, protein loss was thought to be due to giant gastric rugae of the resected stomach. It was concluded that Tc-99m albumin is a valuable means for detection of the site of protein loss in patients with protein-losing gastroenteropathy. This method has several advantages in the clinical setting; it is less time consuming, easy to perform, and provides quantitative and qualitative assessment of protein loss.

Female↗

Mucin-hypersecreting carcinoma of the pancreas.

Five cases of prominent, diffuse dilatation of the main pancreatic duct caused by mucin-hypersecreting carcinoma are reported. Adenocarcinoma was noted mainly within one markedly dilated main pancreatic duct. On endoscopic retrograde pancreatograms, dilated main pancreatic ducts with amorphous or well-defined filling defects resulting from mucin (five patients) or tumor (one patient) were noted. The proximal portion of the main pancreatic duct alone was delineated in three cases because of reflux of contrast material as a result of the presence of excessive mucin and a patulous orifice of the papilla of Vater (major duodenal papilla). Diffuse dilatation of the main pancreatic duct was demonstrated or suggested on computed tomographic (CT) and ultrasound scans. Four patients who underwent operations are alive and free from carcinoma (mean, 50 months after diagnosis). Whenever prominent, diffuse dilatation of the main pancreatic duct is encountered on CT or ultrasound scans, endoscopic retrograde pancreatography is mandatory to permit confirmation or ruling out of mucin-hypersecreting carcinoma of the pancreas.

Adenocarcinoma↗

Molecular aspects of urea cycle enzymes and related disorders.

Amino acid sequence of rat ornithine transcarbamylase (OTC) precursor containing an NH2-terminal presequence of 32 residues was deduced from the cDNA sequence. Comparison with the human and Escherichia coli enzymes indicated that regions containing the putative binding sites for the substrates are highly conserved among the three species. cDNA clones for rat and human liver arginase were isolated and predicted amino acid sequences were compared with that of the yeast enzyme. There are several regions highly conserved among the three species which may be important for catalysis. Several cases of carbamyl phosphate synthetase I and OTC deficiencies were analyzed for enzyme activity, enzyme amount and mRNA activity.

Amino Acid Metabolism, Inborn Errors↗