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Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 595 records · Page 33Linked to original sources
PubMed1994

Tauro alpha-muricholate is as effective as tauro beta-muricholate and tauroursodeoxycholate in preventing taurochenodeoxycholate-induced liver damage in the rat.

Male Wistar rats were infused intravenously with taurochenodeoxycholate (0.4 mumol/min/100 gm) alone (group A) or with one of the three bile salts (tauroursodeoxycholate [group B], tauro beta-muricholate [group C] or tauro alpha-muricholate [group D]) at a rate of 0.2 mumol/min/100/gm for 1 hr. One-hour bile flow and bile salt excretion rates were significantly lower in group A than in the other three coinfused (B, C, D) groups. Biliary 1-hr outputs of lactate dehydrogenase and albumin in the bile, on the other hand, were significantly higher in group A than in the other groups. Plasma concentrations of lactate dehydrogenase at the time of killing (1 hr) were two to three times higher in group A than in the other groups. Although tauro alpha-muricholate does not possess a 7 beta-hydroxy group, the 6 beta-hydroxy group that tauro alpha-muricholate possesses thus appears to be as effective as a 7 beta-hydroxy group in reducing the liver damage caused by toxic bile salts such as taurochenodeoxycholate. The so-called hepatoprotective effects of tauroursodeoxycholate and tauro beta-muricholate found in previous studies may require explanation(s) other than the presence of a 7 beta-hydroxy group in their molecular structures.

Albumins↗
PubMed1994

[Early phase II clinical study of KW-2307 in patients with lung cancer. Lung Cancer Section in KW-2307 Study Group].

A multicenter early Phase II clinical study of KW-2307, a new vinca alkaloid derivative, in patients (pts) with lung cancer was conducted in 15 hospitals. Ninety-seven pts were enrolled, among whom 95 were eligible. Seventy of the eligible pts had non-small cell cancer (NSCLC) and 25 had small cell cancer (SCLC). PR was obtained in 13 (18.6%) of NSCLC pts and 3 (12%) of SCLC pts. Only those who had no previous chemotherapy showed PR in NSCLC pts, and the response rate in these pts was 29.5% (13/44). As to the correlation between dosage and tumor effect, a better effect was exhibited at higher doses, with response rates of 21.7% (5/23) and 38.1% (8/21) at 20 mg/m2 and 25 mg/m2, respectively. The major adverse effect of this drug was leukopenia (neutropenia), which was Grade 3 or 4 in many cases. Recovery from this complication, however, was rapid. Other adverse effects included mild hepatic dysfunction, anorexia, nausea/vomiting, fever, general fatigue, phlebitis and constipation. The incidence of peripheral nervous disorder such as the paresthesia commonly observed with vinca alkaloids, was as low as 10%, and the symptoms, if any, were mild.

Adult↗
PubMed1994

[Immunohistochemical study of Helicobacter pylori and mononuclear cells in the gastric mucosa of patients with gastritis or peptic ulcer].

The distribution and localization of Helicobacter pylori (HP) and mononuclear cells (MNC) in the gastric mucosa were investigated immunohistochemically in 120 patients with gastritis or peptic ulcer. HP was detected in the gastric mucosa of 58% of 40 gastritis patients, 82% of 56 gastric ulcer (GU) patients, and 88% of 24 duodenal ulcer (DU) patients. In the HP-positive mucosa, cells positive for IgG or IgA were increased significantly when compared to the HP-negative mucosa. Neutrophils and eosinophils were also increased under the HP-infected surface and therefore these cells were likely involved in the mucosal damage. Enhancement of the expression of HLA-DR antigen was observed in the gastric epithelium with HP infection and it was associated with a significant increase of lymphoid follicles and B cells in the mucosa. In comparison with the HP-infected mucosa of gastritis patients, the number of MNC were increased significantly in the mucosa of both DU and GU patients. The number of HP in the gastric mucosa of DU patients was significantly higher than those of both gastritis and GU patients. In addition, the grade of the infiltration of MNC and IgA positive cells were always greater in DU than in gastritis, regardless of the number of HP. These findings suggested that activation of the local immunity in the gastric mucosa of gastritis and peptic ulcer patients by HP infection may participate in the pathogenesis of gastroduodenal mucosa damage.

Adult↗
PubMed1994

Local recurrence after complete resection for non-small-cell carcinoma of the lung. Significance of local control by radiation treatment.

Of 471 patients undergoing a complete resection for non-small-cell carcinoma of the lung between 1972 and 1989, 40 patients (8.5%) had local recurrences without extrathoracic distant metastasis. Excluding 8 patients who had malignant pleural effusion, we selected 32 patients (24 with hilar-mediastinal lymph node, 6 with bronchial stump, and 2 with chest wall recurrence) from the 40 patients and assessed the significance of local control by radiotherapy. The median length of survival after disease recurrence for these 32 patients was 19 months. Of 29 patients given radiation treatment, 16 who responded to the treatment survived significantly longer than nonresponders (median survival time 27 months versus 6 months, p < 0.01). Univariate analyses of survival after recurrences in relation to various factors revealed that sex and disease-free intervals were significant prognostic factors (p < 0.05) other than the effect of radiotherapy. A multivariate analysis showed that the effect of radiotherapy was the predominant prognostic factor. From these results, we conclude that local control with radiation is beneficial in patients with solely locally recurrent tumors in terms of improved survival.

Adult↗
PubMed1994

Analysis of hepatic vein waveform by Doppler ultrasonography in 100 patients with portal hypertension.

OBJECTIVES: We classified the Doppler waveform seen in patients with portal hypertension and examined the associations of the waveform type with the diagnosis of Budd-Chiari syndrome and severity of the liver cirrhosis. METHODS: The Doppler pattern of right and left hepatic veins in 100 consecutive Japanese patients with portal hypertension and esophagogastric varices was classified into six types: I, triphasic waveform; II, biphasic waveform without reversed flow; III, decreased amplitude of phasic oscillations; IV, flat waveform with fluttering; V, completely flat waveform with fluttering; VI, no waveform. All patients underwent computed tomography and magnetic resonance imaging. Patients in whom hepatic vein waveform showed type IV, type V, or type VI, positively underwent hepatic venography and inferior vena cavography. RESULTS: Type I was seen in 31 of 100 patients, type II in 35, type III in 17, type IV in eight, type V in four, and type VI in five. Types I-IV waveform indicated no lesion in hepatic veins and inferior vena cava, type V indicated stenosis of hepatic veins or occlusion of inferior vena cava, and type VI, occlusion of hepatic veins. For one patient with type V hepatic veins, balloon angioplasty was done, and the waveform changed from type V to type II. Examining the relationship between hepatic vein waveform and the Child-Pugh score, liver function of type IV cases was worse than that of type I cases in 66 cirrhotic patients without hepatocellular carcinoma (p < 0.05). There was no clear relationship between hepatic vein waveform and portal venous perfusion, as based on Nordlinger's grade. CONCLUSIONS: Our classification of hepatic vein waveform in Doppler ultrasonography is useful in diagnosing Budd-Chiari syndrome, in judging the efficiency of treatment for hepatic vein lesions, and in assessing severe liver function in cirrhotic patients.

Adult↗
PubMed1993

C fiber generates a slow Na+ spike in the frog sciatic nerve.

The present study was carried out to examine the properties of A and C fibers in the bullfrog sciatic nerves by applying several agents through perfusing solutions between stimulating and recording electrodes. The compound action potentials (CAPs) of A beta and A delta fibers were tetrodotoxin (TTX)-sensitive and were abolished in Na(+)-free solution. However, C fiber CAP was TTX-insensitive although CAP disappeared in Na(+)-free solution. Moreover, C fiber CAP was not blocked by Ca2+ channel blockers and its chronaxy (2 ms) and conduction velocity (0.70 m/s) indicate that the time constant of C fiber CAP is relatively large (2.88 ms). These suggest that a slow Na+ channel, which is TTX-resistant, contributes to C fiber action potentials.

Action Potentials↗
PubMed1993

Immunohistochemical distribution of amyloid precursor protein during normal rat development.

This study focused on the immunohistochemical identification of the beta/A4 amyloid precursor protein (APP) in various developmental stages of both the rat central nervous system (CNS) and the peripheral nervous system (PNS). A comparative study with myelin basic protein (MBP) and synaptophysin (SYP) facilitated the understanding of neuronal maturation and synaptogenesis on both prenatal and postnatal development. Our immunohistochemical study revealed APP to be widely distributed through the nervous system while existing mainly in the cytoplasm, dendrites and axons of the neurons. However, immunoreactivity was also observed in either the ependymal cells or the choroid plexus epithelial cells. Our immunostaining was carried out by the hydrated autoclaving method and revealed the expression of APP at embryonic day 15 in the neuron of the mesencephalic nucleus of the trigeminal nerve and the anterior horn of the spinal cord, trigeminal and spinal ganglion, ependymal cells and the choroid plexus. We thus observed dramatic changes of APP expression in the cerebellum from the embryonic stage. The maturation of synaptogenesis in the cerebellar molecular layer was parallel to the extension of the dendrites of Purkinje cells, which revealed immunoreactivity for APP. These findings suggested that APP played an important role in neuronal maturation and synaptogenesis. Thus, APP is considered to be a useful marker for neuronal development.

Amyloid beta-Protein Precursor↗
PubMed1993

Establishment of lung cancer cell line producing parathyroid hormone-related protein.

Parathyroid hormone-related protein (PTHrP) producing cell line (KCC-C1) was established from malignant pleural effusion of a patient with squamous cell lung carcinoma. Hypercalcemia and granulocytosis were noted in the patient. The serum level of PTHrP, measured by N-terminal specific radioimmunoassay, was 110 pg/ml (normal < 20 pg/ml). The established KCC-C1 tumor cells proved to have PTHrP RNA transcripts and produce a large amount of PTHrP. Besides the production of PTHrP, the culture medium contained a significant level of interleukin 1 (IL-1). However, tumor necrosis factor or colony stimulating factor was not defected. Transplantation of KCC-C1 tumor cells into nude mice resulted in tumor formation with hypercalcemia. As IL-1 is also known to have bone-resorbing activity, KCC-C1 which may prove valuable in the study of the interaction between PTHrP and IL-1 for induction of hypercalcemia.

Animals↗
PubMed1993

The effect of caloric restriction on the lateral diffusion constant of hepatocyte membrane proteins in C57BL/6 male mice of different ages: FRAP studies on liver smears.

The lateral mobility of proteins in hepatocyte plasma membranes was compared in calorically restricted and ad libitum (AL)-fed C57BL/6 male mice in age groups from 7 to 28 months. Caloric restriction was achieved by means of the every-other-day (EOD) feeding regimen, maintained for various periods from 1 to 15 months. Protein lateral diffusion constant (D) in hepatocyte membranes was measured by means of fluorescence recovery after photobleaching (FRAP) in liver smears. The peroxide-induced autofluorescence (PIAF) was utilized as a fluorescent label. A mild (1 mM for 10 min) H2O2 treatment of liver smears produces oxidation of riboflavin that is bound to all proteins of the cell membrane. Using this technique, the average lateral diffusion constant (D) and the fractional recovery (FR) of these proteins can be measured. EOD feeding resulted in a significant decrease in body weights and also a significant increase in the values of D in all age groups after 1 month of EOD feeding. After 3.5 months of EOD feeding a further increase of D was observed (up to about 15%). Nevertheless no further change in D occurred if the EOD feeding was maintained for 6.5 or even 15 months. The negative linear age correlation of D observed in the AL-fed animals was present also under the EOD feeding; however, the whole regression equation shifted towards higher values. These experiments indicate that caloric restriction influences the lateral diffusion constant of membrane proteins in hepatocytes. The results are interpreted as a result of an increased protein turnover caused by the caloric restriction.

Aging↗
PubMed1993

Two truncated forms of rat insulin receptor-related receptor.

The insulin receptor-related receptor (IRR) (1271 amino acids) is expected to have unique functions as a novel member of the insulin receptor family. In this paper, we report two alternatively spliced variants of rat IRR mRNA, which are predicted to encode two truncated forms of IRR, sIRR-1 (410 amino acids) and sIRR-2 (469 amino acids). The amino acid sequence of sIRR-1 is identical to the N-terminal 410-amino acid sequence of IRR. sIRR-2 has an additional 59-amino acid insertion in the C-terminal region. Both truncated forms retain the N-terminal and cysteine-rich domains but lack the transmembrane and intracellular tyrosine kinase domains, indicating that the truncated forms are the secreted forms. The translation products of the truncated form mRNAs were detected in the stomach and kidney by Western analysis. However, the physiological significance of the secreted forms remains to be elucidated.

Alternative Splicing↗
PubMed1993

Cloning, expression and characterization of horse L-ferritin in Escherichia coli.

Horse L-ferritin cDNA was cloned from horse liver, and the base sequence was determined. The L-ferritin was expressed using pTZ18U encoding lac promoter, and found to possess an additional 8-amino acid sequence at the N-terminus as compared with commercially obtained horse spleen (natural) ferritin. It was determined that there was Pro at position 94 in both the recombinant and natural L-ferritin, although it was previously reported that Leu was in this position in the natural species. Transmission electron microscopy showed that this recombinant ferritin formed a 24-mer shell.

Amino Acid Sequence↗
PubMed1993

Nicotinic acetylcholine receptor mRNAs in myasthenic thymuses: association with intrathymic pathogenesis of myasthenia gravis.

Reverse transcription and the polymerase chain reaction showed that the alpha-, beta- and gamma-subunit genes of nicotinic acetylcholine receptor (AChR) in human skeletal muscle were expressed in myasthenia gravis (MG) thymuses (3 thymomas and 7 hyperplastic thymuses). A study of the expression of these subunit mRNAs in a variety of human tissues showed that alpha-subunit mRNA was expressed in human thymus and cerebral cortex, and that all three subunits were expressed only in human child thymus. Our results suggest that a complete AChR similar to extrajunctional (embryonic) muscle AChR is expressed in MG thymuses and that intrathymic AChR might be the primary antigen which induces autoimmune responses to muscle AChR.

Base Sequence↗
PubMed1993

Central effects of interleukin-1 on blood pressure, thermogenesis, and the release of vasopressin, ACTH, and atrial natriuretic peptide.

To assess the central role of interleukin 1-beta (IL-1 beta) in the release of ACTH, vasopressin (AVP) and atrial natriuretic peptide (ANP) and in the regulation of blood pressure and thermogenesis, 3 ng (0.173 pM) x 100-1 x BW-1 (LIL), 30 ng (1.73 pM) x 100g-1 x BW-1 (MIL), and 150 ng (8.63 pM) x 100g-1 x BW-1 (HIL) of human IL-1 beta dissolved in sterile saline were injected intracerebroventricularly to conscious rats. In the control rats, saline alone (5 microliters) was administered. In three other groups, rats were pretreated with indomethacin, a cyclooxygenase inhibitor, given i.v. (1 mg x 100g-1 x BW-1); medium and high doses of IL-1 beta or its vehicle were given. In the LIL group, IL-1 beta increased blood pressure, body temperature and plasma AVP and ANP without any changes in heart rate (HR) and plasma ACTH. In the MIL group, plasma ACTH was increased, and changes in the other parameters were similar to those in the LIL group. In the HIL group, however, the pressor and thermogenetic responses were attenuated; plasma AVP, ACTH, and ANP were increased; and HR was unchanged. In the control (CON) group, none of these parameters was changed throughout the studies. Indomethacin abolished the AVP and ACTH responses to IL-1 beta, but potentiated the pressor and hypothermic responses and increased plasma ANP. These data suggest that the actions of IL-1 beta on AVP and ACTH release and thermogenesis, but not on blood pressure and the release of ANP, are modulated by the stimulated central production of prostaglandins.

Adrenocorticotropic Hormone↗
PubMed1993

Detailed genetic and physical map of the 3p chromosome region surrounding the familial renal cell carcinoma chromosome translocation, t(3;8)(p14.2;q24.1).

Extensive studies of loss of heterozygosity of 3p markers in renal cell carcinomas (RCCs) have established that there are at least three regions critical in kidney tumorigenesis, one most likely coincident with the von Hippel-Lindau gene at 3p25.3, one in 3p21 which may also be critical in small cell lung carcinomas, and one in 3p13-p14.2, a region which includes the 3p chromosome translocation break of familial RCC with the t(3;8)(p14.2;q24.1) translocation. A panel of rodent-human hybrids carrying portions of 3p, including a hybrid carrying the derivative 8 (der(8)(8pter-->8q24.1::3p14.2-->3pter)) from the RCC family, have been characterized using 3p anchor probes and cytogenetic methods. This 3p panel was then used to map a large number of genetically mapped probes into seven physical intervals between 3p12 and 3pter defined by the hybrid panel. Markers have been physically, and some genetically, placed relative to the t(3;8) break, such that positional cloning of the break is feasible.

Animals↗
PubMed1993

Functional expression and characterization of a Xenopus laevis peptidylglycine alpha-amidating monooxygenase, AE-II, in insect-cell culture.

The alpha-amidating reaction of peptide hormones is a two-step process which is catalyzed by peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidylhydroxyglycine N-C lyase (PHL). There are three types of mRNA for these amidating enzymes in Xenopus laevis, namely AE-I, AE-II and AE-III. AE-I encodes only PHM and AE-III encodes both PHM and PHL. AE-II seems to encode subtypes of both PHM and PHL. While AE-II mRNA is present in high amounts in frog skin, the actual enzymes originating from AE-II have not been detected. When we expressed AE-II in cultured insect-cells using the baculovirus expression vector system, the expressed enzyme was specifically localized to the membrane fraction due to its hydrophobic transmembrane domain. Alternatively, when the transmembrane-domain-deleted AE-II (Met1-Ile731) was expressed, the enzyme was secreted into the culture medium; this secreted enzyme was purified to homogeneity by a simple two-step procedure. We have verified that the reaction product of the purified enzyme was the amidated peptide, indicating that AE-II has the ability to catalyze the entire amidating reaction.

Amino Acid Sequence↗