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Biomedical subjects

T Baba

Publications and source records attributed to T Baba.

At least 91 records · Page 5Linked to original sources
PubMed1997

Diabetic nephropathy. Its relationship to hypertension and means of pharmacological intervention.

Hypertension and diabetes mellitus are common chronic conditions which frequently coexist. Diabetic nephropathy is a major cause of elevated blood pressure in patients with insulin-dependent diabetes mellitus (IDDM). Diabetic nephropathy, arterial sclerosis, obesity and association of essential hypertension can be the causes of hypertension in patients with non-insulin-dependent diabetes mellitus (NIDDM). Ambulatory blood pressure monitoring has revealed that the nocturnal fall of blood pressure is blunted in patients with diabetic nephropathy. A blunted diurnal blood pressure variation is seen in microalbuminuric diabetic patients and even in some normoalbuminuric patients. Accumulating data suggest that normalisation of blood pressure in hypertensive IDDM patients is most important to minimise the loss of kidney function. Angiotensin converting enzyme (ACE) inhibitors have been reported to be effective in postponing the development of nephropathy and in slowing its progression. Whether only ACE inhibitors have such beneficial renal effects on diabetic nephropathy is under discussion. While many studies have suggested that insulin resistance and hyperinsulinaemia are related to an elevated blood pressure in hypertensive patients, there does not seem to be enough evidence to prove that insulin per se can raise blood pressure in humans. Neither an insulin infusion within a physiological range nor sustained hyperinsulinaemia and insulin resistance (e.g. patients with insulinoma, cystic ovary syndrome) have been associated with an elevated blood pressure. Insulin resistance in some hypertensive patients may be a consequence of a decreased blood flow due to an increased peripheral resistance. Preliminary evidence suggests that low birth weight or impaired fetal growth is related to hypertension and NIDDM. Familial clustering of diabetic nephropathy suggests the contribution of genetic susceptibility and/or environmental inheritance. The frequent association of nephropathy with hypertension has led to research on the genes related to hypertension (ACE, angiotensinogen). Nevertheless, to date no reliable and clinically useful genetic marker has been found. Attempts to correct the metabolic abnormalities derived from diabetes are a new topic in the treatment of diabetic nephropathy. The effects of HMG CoA reductase inhibitors (antihypercholesterolaemic drugs), aldose reductase inhibitors (inhibitors of the polyol pathway) and glycation inhibitors (inhibitors of formation of advanced glycosylation end-products) on diabetic nephropathy have been evaluated in animal studies and in some clinical trials. Thus far, results with HMG CoA reductase and aldose reductase inhibitors have been somewhat conflicting. The potential therapeutic role of glycation inhibition in the treatment of diabetes deserves further study.

Adrenergic beta-Agonists↗
PubMed1997

Erythromycin derivative improves gastric emptying and insulin requirement in diabetic patients with gastroparesis.

OBJECTIVE: To evaluate the effect of the erythromycin derivative EM523L on gastric emptying and postprandial insulin requirement in insulin-dependent diabetic patients with severe gastroparesis. RESEARCH DESIGN AND METHODS: In six IDDM patients with severe gastroparesis (two men and four women, mean age 44.5 years [range 36-53]), the insulin infusion pattern during feedback control with an artificial endocrine pancreas device (Biostator) after intake of a test meal, the retention rate of residual isotope ([99m]Tc-labelled Sn-colloid) in the stomach, and the time-concentration curve of plasma acetaminophen as the marker for liquid emptying were studied with EM523L or a control placebo RESULTS: Time courses of insulin infusion rates peaked within 120 min after intake of the test meal in the EM523L phase, whereas no apparent peak rates were observed in the control phase. The total amount of insulin required in the first 90 min postprandial was significantly greater in the EM523L phase than in the control phase. EM523L significantly decreased the residual isotope ratio in the stomach at > or =50 min postprandial and increased the plasma acetaminophen concentrations at 30-120 min postprandial, compared with respective values in the control phase. CONCLUSIONS: Preliminary results obtained from a small number of patients suggest that EM523L or erythromycin analogs, which have agonistic activity to motilin receptors as well as no antibacterial effect, may be useful to accelerate gastric emptying and improve insulin requirement patterns, thereby establishing more stable glycemic control.

Acetaminophen↗
PubMed1997

Identification of rat and human cytochrome P450 forms involved in the metabolism of the thromboxane A2 receptor antagonist (+)-S-145.

(+)-S-145 [5-(+)-(Z)-7-[(1R, 2S, 3S, 4S)-3-phenylsulfonylaminobicyclo[2.2.1]hept-2-yl]-heptenoic acid] and its beta-oxidized metabolites [two [bisnor or dihydro (DH)-bisnor] or four (tetranor) carbon-shortened products at the carboxyl side chain] are hydroxylated at the C-5 or C-6 position of the bicyclo ring by microsomal monooxygenases. We investigated the oxidative metabolism of (+)-S-145 and its beta-oxidized metabolites with liver microsomes from rats and humans to identify which cytochrome P450 (P450) forms are involved in these reactions. In rats, phenobarbital or dexamethasone treatment significantly increased 5- and 6-hydroxylation activities toward (+)-S-145 and its beta-oxidized metabolites, suggesting the involvement of P4503A forms. Immunoinhibition studies suggested that P4503A2 was mainly responsible for the 5-hydroxylation of (+)-S-145, bisnor, and DH-bisnor and the 6-hydroxylation of bisnor and tetranor. Furthermore, P4502C6, a phenobarbital-inducible 2C form in the rat, was involved in the 6-hydroxylation of (+)-S-145, bisnor, and DH-bisnor. P4502C11, the major constitutive form (male rats), was partly involved in the 5-hydroxylation of DH-bisnor and the 6-hydroxylation of bisnor and DH-bisnor. Reconstitution studies with purified human enzymes and immunoinhibition studies suggest that P4503A4 is primarily involved in the 5-hydroxylation of (+)-S-145 and bisnor and the 6-hydroxylation of tetranor; P4502C9/10 mainly catalyzed the 5-hydroxylation of tetranor and the 6-hydroxylation of (+)-S-145. Results of the present study indicated that the same subfamily P450 forms are responsible for the oxidative metabolism of (+)-S-145 in rats and humans. P4503A enzymes were shown to be involved in the formation of 6-hydroxy tetranor, the main metabolite of S-1452 in vivo.

Animals↗
PubMed1997

[Interferon treatment for hepatitis G virus infection in patients with chronic hepatitis C].

Clinical features of HGV infection as a novel virus infection have not yet been clarified enough. We studied the implication of HGV in the activity of hepatitis and the sensitivity of HGV to IFN. We treated 10 HGV RNA positive patients with chronic hepatitis C with IFN. HGV RNA was identified in serum by RT-PCR method using the primer derived from the base sequences of the NS5 region of HGV genome. HGV RNA became negative in the all of 10 patients during IFN treatment, but returned to be positive again in the all patients after the completion of IFN treatment. In 5 of 10 patients, HCV RNA became persistently negative. In 3 of these 5 patients, ALT was continuously normal and hepatitis subsided biochemically and clinically after IFN treatment. We assume that HGV is sensitive to IFN, but could not be implicated in hepatitis or liver damage.

Adult↗
PubMed1997

CT and MR findings of denervated tongue after radical neck dissection.

PURPOSE: To describe the CT and MR findings in the denervated tongue after a radical neck dissection. METHODS: We retrospectively evaluated the radiologic findings in seven patients who had hypoglossal paralysis following radical neck dissection. None of the patients had clinical or radiologic evidence of tumor recurrence. RESULTS: The side of the tongue operated on showed low density on CT scans. At MR imaging, denervated tongues were clearly seen as hyperintense relative to muscle on T2-weighted images; on T1-weighted images, the signal was hypointense to hyperintense, representing increased extracellular water or fatty degeneration. CONCLUSION: In patients who have undergone a neck dissection for a malignant process, abnormal imaging findings in the tongue not only might indicate a recurrence of tumor involving the hypoglossal nerve but also suggest the possibility of postoperative change. Our findings emphasize the importance of the denervated tongue in differentiating inflammatory from neoplastic diseases of the the tongue.

Adult↗
PubMed1997

Immunocytochemical study of dystrophin localization in cone cells of mouse retinas.

PURPOSE: Previously, the authors reported that dystrophin was observed under the rod cell membranes in rat retinas. However, it was not determined whether dystrophin is located in cone cells. In the current study, the authors clarify dystrophin localization in cone cells of mouse retinas. METHODS: Immunoblotting, confocal laser scanning microscopy, and immunoelectron microscopy were used to investigate retinal dystrophin with a monoclonal antibody raised against the human dystrophin C-terminus. RESULTS: Immunoblotting analysis showed some immunoreactive bands from retinal extracts. Confocal images indicated two different immunostaining patterns: One was a tiny dot, and the other was a larger, aggregated dot. Immunoelectron microscopy revealed that retinal dystrophin was localized in cone cells as well as in rod cells. CONCLUSIONS: Retinal dystrophin is a common component of cone and rod cells and probably is related to the physiological function of photoreceptor cells.

Animals↗
PubMed1996

A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 28.0-40.1 min region on the linkage map.

The 569,750 base pair sequence corresponding to the 28.0-40.1 min region on the genetic map of Escherichia coli K-12 (W3110) was determined. This region includes the replication terminus region and contained at least 549 potential open reading frames. Among them, 160 (29%) were previously reported, 174 (32%) were homologous to other known genes, 102 (18%) were identical or similar to hypothetical genes registered in databases, and the remaining 113 (21%) did not show a significant similarity to any other gene. Of interest was the finding of a large number of genes and gene clusters in and near the replication termination region which had been thought to be genetically silent. Those included a cluster of genes for fatty acid beta-oxidation, the third copy of the pot (spermidine/putrescine transport system) gene cluster, the second dpp (dipeptide transport system) operon, the second dsm (anaerobic dimethyl sulfoxide reductase) operon, a cluster of fim (fimbrial) genes and a DNA helicase-like gene with a high molecular weight. In addition, we found the dnaC- and dnaT-like genes in the cryptic prophage, Rac, and a number of genes originated probably from plasmids.

Chromosome Mapping↗
PubMed1996

A 460-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 40.1-50.0 min region on the linkage map.

The 465,813 base pair sequence corresponding to the 40.1-50.0 min region on the genetic map of Escherichia coli K-12 (W3110) was determined. Analysis of the sequence revealed that this region contained at least 466 potential open reading frames, of which 187 (40%) were previously reported, 105 (23%) were homologous to other known genes, 103 (22%) were identical or similar to hypothetical genes registered in databases, and the remaining 71 (15%) did not show a significant similarity to any other gene. At the 45.2-46.0 min region, we found a very large cluster of about 30 genes, whose functions are involved in the biosynthesis of polysaccharides as the components of outer membranes. In addition, we identified a new asn-tRNA gene, designated asnW, between the asnT and asnU genes and a new lysogenic phage attachment site as the cis-element.

Attachment Sites, Microbiological↗
PubMed1996

Target cell specificity of a bacteriocin molecule: a C-terminal signal directs lysostaphin to the cell wall of Staphylococcus aureus.

Microbial organisms secrete antibiotics that cause the selective destruction of specific target cells. Although the mode of action is known for many antibiotics, the mechanisms by which these molecules are directed specifically to their target cells hitherto have not been described. Staphylococcus simulans secretes lysostaphin, a bacteriolytic enzyme that cleaves staphylococcal peptidoglycans in general but that is directed specifically to Staphylococcus aureus target cells. The sequence element sufficient for the binding of the bacteriocin as well as of hybrid indicator proteins to the cell wall of S.aureus consisted of 92 C-terminal lysostaphin residues. Targeting to the cell wall of S.aureus occurred either when the hybrid indicator molecules were added externally to the bacteria or when they were synthesized and exported from their cytoplasm by an N-terminal leader peptide. A lysostaphin molecule lacking the C-terminal targeting signal was enzymatically active but had lost its ability to distinguish between S.aureus and S.simulans cells, indicating that this domain functions to confer target cell specificity to the bacteriolytic molecule.

Bacterial Outer Membrane Proteins↗
PubMed1996

A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map.

The 718,122 base pair sequence of the Escherichia coli K-12 genome corresponding to the region from 12.7 to 28.0 minutes on the genetic map is described. This region contains at least 681 potential open reading frames, of which 277 (41%) have been previously identified, 147 (22%) are homologous to other known genes, 139 (20%) are identical or similar to the hypothetical genes registered in databases, and the remaining 118 (17%) do not show a significant similarity to any other gene. In this region, we assigned a cluster of cit genes encoding multienzyme citrate lyase, two clusters of fimbrial genes and a set of lysogenic phage genes encoding integrase, excisionase and repressor in the e14 genetic element. In addition, a new valine tRNA gene, designated valZ, and a family of long directly repeated sequences, LDR-A, -B and -C, were found.

DNA, Bacterial↗
PubMed1996

Boar proacrosin expressed in spermatids of transgenic mice does not reach the acrosome and disrupts spermatogenesis.

Transgenic mice that express boar proacrosin were produced to examine mechanisms for targeting hydrolytic enzymes to the acrosome. A 2.3 kb transgene was constructed by ligating the cDNA for boar preproacrosin with the mouse protamine 2 promoter region. Six founder mice that incorporated the transgene were identified by polymerase chain reaction and Southern blot analysis. Northern blots indicated that the two male founders (Ac.2 and Ac.5) and male progeny from three female founders (Ac.3, Ac.4, Ac.6) expressed the transgene mRNA in testis, but not in somatic tissues. In these transgenic animals boar proacrosin was detected by immunohistochemistry in condensing spermatids, but was not localized in the acrosome. This acrosomal targeting defect of the transgene product may result from its delayed expression during the later steps of haploid differentiation. Furthermore, both male founders and all Ac.4 and Ac.6 males were infertile, as determined by multiple matings for at least 2 months. Ac.3 males were either infertile or rarely transmitted the transgene to their offspring. The infertile males mated, produced copulatory plugs, and had seminal vesicle weights and testosterone levels within the normal range. However, they produced significantly fewer spermatozoa and had lower testis weights than controls. Although the mitotic and meiotic phases of spermatogenesis appeared normal by histological criteria, condensing spermatids were missing from most tubules, and multinucleated cells were present in the lumen of seminiferous tubules and in the epididymis. We hypothesize that boar proacrosin which fails to reach the acrosome is activated in these transgenic mice, and that its proteolytic activity disrupts spermatogenesis during spermatid formation.

Acrosin↗
PubMed1996

Determination of enamel protein synthesized by recombined mouse molar tooth germs in organ culture.

Epithelial-mesenchymal interaction is a prerequisite for tooth morphogenesis. To study this interaction, inner enamel epithelium and dental papilla mesenchyme of molar tooth germs from a 16.5-day mouse embryo were dissociated enzymatically and cultured alone or after recombination. Characteristic matrix protein synthesized and secreted by recombined tooth germ was determined quantitatively by enzyme-linked immunosorbent assay. The protein was detected in the culture of recombined tooth germ but not of dissociated enamel epithelium alone. The amount of enamel protein increased until 8 days in culture. Morphological differentiation of the recombined epithelial rudiment into ameloblasts and enamel protein production were confirmed.

Ameloblasts↗