Reexamination of chromosomal loci of human muscle actin genes by fluorescence in situ hybridization.
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Biomedical subjects
Publications and source records attributed to T Miwa.
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The expression of EGF/EGFR in 47 laryngeal surgical specimens from 44 patients was examined. PCNA analysis as an index of proliferating cells was also performed in 32 cases of laryngeal cancer, six cases of pre-cancerous lesions and nine cases of normal laryngeal mucosa. EGFR failed to show a significant correlation with tumour behaviour, but EGF expression was statistically significantly higher in malignant (SCC) than in non-malignant tissues (pre-cancerous and normal tissues) (p < 0.006), and PCNA also showed a statistically significant difference (p < 0.016) between the two. In malignant tissues when EGF/EGFR in 'double-positive' and 'double-negative' cases was compared, a statistically significant difference in PCNA was found (p < 0.029); but this was not seen in non-malignant tissues. Our results support the hypothesis that an autocrime mechanism exists in laryngeal cancer and in this mechanism EGF may play an important role in tumour progression, especially when EGFR is overexpressed.
Helicobacter pylori eradication therapy combining amoxicillin (AMPC), plaunotol (PL), and a proton pump inhibitor (PPI) was examined as an alternative to triple therapy, which has a high rate of side effects and low patient compliance. Thirty-two H. pylori-positive patients (24 men, 8 women) with duodenal ulcers were examined. The diagnosis of H. pylori infection was made by the urease test on specimens biopsied from two sites in the stomach. Simultaneously, the IgG antibody against H. pylori was measured by the EIA method. The therapeutic regimen was lansoprazole (LPZ) 30 mg q.d. (6 weeks) and AMPC 1,500 mg t.i.d. (2 weeks) plus PL320 mg b.i.d. (6 weeks). The rate of ulcer healing was judged endoscopically after 6 weeks. Cases that become urease-negative after the cessation of the therapy were defined as having achieved clearance, and those negative after 1 month as eradication. Within 6 weeks, 31 of 32 patients had healed ulcers. All patients were H. pylori antibody-positive before therapy. The clearance rate was 71.9% (23/32) and the eradication rate was 45.8% (11/24). Adverse effects were observed only in one case. We conclude that combination therapy with LPZ, AMPC, and PL has a high therapeutic effect on ulcer healing and moderate effectiveness for eradication of H. pylori.
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The effects of 7-(4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro-2 (1H)- quinolinone (OPC-14597), a derivative of the dopamine (DA) autoreceptor agonist 7-(3-[4-(2,3-dimethylphenyl)piperazinyl]propoxy)-2(1H)-quinolinone (OPC-4392), on DA receptors were biochemically and behaviorally studied and compared with those of OPC-4392. Both OPC-14597 and OPC-4392 inhibited reserpine- and gamma-butyrolactone (GBL)-induced increase in tyrosine hydroxylase activity in the mouse and rat brain. The effects of OPC-14597 were comparable to those of OPC-4392 and were completely antagonized by haloperidol. OPC-14597, unlike apomorphine, did not evoke postsynaptic DA receptor-stimulating behavioral signs such as hyperlocomotion in the reserpinized mice and contralateral rotation in rats with unilateral striatal 6-hydroxydopamine lesions. Both OPC-14597 and OPC-4392 inhibited such apomorphine-induced postsynaptic behavioral changes as stereotypy and hyperlocomotion in mice and rats and rotation in rats with unilateral striatal kainic acid lesions. The anti-apomorphine effects of OPC-14597 were about 30 to 140 times greater than those of OPC-4392 and were observed at doses that inhibit the increases in tyrosine hydroxylase activity. The affinities of OPC-14597 for 3H-spiperone-labeled D2 receptors in the rat frontal cortex, limbic forebrain and striatum were higher than those of OPC-4392. These results suggest that OPC-14597 is a unique antipsychotic drug candidate, being a DA autoreceptor agonist that has a stronger postsynaptic D2 receptor antagonistic activity than that of OPC-4392.
In Japan the number of patient infected with M. avium complex (MAC) has been increasing in contrast to a decrease of pulmonary tuberculosis. DNA probe method enabled us be able to differentiate an isolated MAC into M. avium and M. intracellulare. From 1991 to 1992, we performed an investigation to apply this new technique of the DNA probe method on 52 patients of atypical mycobacteriosis diagnosed as infected with MAC by the ordinary method at the Higashi Nagoya National Hospital. The group consisted of 27 males and 25 females. M. avium infection was found in 39 patients (M. avium group) and M. intracellulare in 16 patients (M. intracellulare group). No significant gender difference was found between two groups. The M. avium group showed more complications in contrast to the M. intracellulare group. As complications in the M. avium group, pulmonary aspergillus infection, bacterial pneumonia and bronchiectasis were found in 4, 3 and 2 cases, respectively. The rate of drug resistance to antituberculosis drugs was high in the both groups. Chemotherapy with isoniazid (INH) rifampin (RFP) and streptomycin (SM) in five patients, that with INH, RFP and ethambutol (EB) in three were found to be effective after 4 months treatment. Three patients in M. avium group died of respiratory failure, aspergillus infection and renal failure. In contrast the prognosis of patients in the M. intracellulare group seemed to be better as there was no fatal case. We conclude that DNA probe method is useful to differentiate between M. avium and M. intracellulare, and enable us to select more appropriate selection of the chemotherapy and to assess of the prognosis.
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Changes in gastric acid secretion and fasting gastrin levels (FGL) during the healing of duodenal ulcers were investigated. Duodenal ulcers were classified into three stages, with regard to healing, active, healing, and healed (scar). As controls, 49 individuals without gastro-duodenal lesions were used. We found that gastric acid secretion was highest during the active stage, thereafter decreasing during the healing and healed stages. Gastric acid secretion was lowest in the normal subjects, and significant differences were found between the 3 stages of the duodenal ulcers. FGL was also highest in the active stage, thereafter decreasing during the healing and healed stages. In the follow-up of 10 doudenal ulcer patients, gastric acid secretion and FGL were higher in the active than in the healed stage. It was concluded that gastric acid secretion and FGL change during the healing of duodenal ulcers. The increase of gastric acid secretion and FGL seen in the active stage appears to be implicated in the pathogenesis of the duodenal ulcer.
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The first case of spontaneous mediastinal emphysema was reported by Hamman et al. in 1939. It is a rare condition that primarily occurs in young adults. In many instances, spontaneous mediastinal emphysema is caused by yelling, shouting or active exercise, but the cause is often unknown. It is rare for cases of spontaneous mediastinal emphysema to recur. Recently, we experienced a recurrent case of spontaneous mediastinal emphysema in a patient with a duodenal ulcer. Vomiting appeared to be the cause of the recurrence in our patient. Of the 58 patients with spontaneous mediastinal emphysema who have been reported in Japan so far, recurrences were documented only in our patient and two others.
Four intraventricular central neurocytomas were studied histopathologically and intriguing findings were obtained with regard to the histogenesis of this tumor. The cases included 3 males and 1 female aged 17-25. The tumors had developed in the regions from the lateral to the third ventricles and were surgically removed in all the cases. A honeycomb appearance was recognized on H&E staining, and the calcification and latticed vascular findings closely mimicked the appearance of oligodendroglioma. A characteristic wide eosinophilic fibrous stroma was observed frequently. Immunohistochemically, all four cases were NSE-positive and strongly synaptophysin-positive, and by electronmicroscopy, neurosecretory granules and microtubules were observed in all cases and typical synapse structures in 2 cases. GFAP immunoreactivity and glial differentiation, including ependymal cells were exhibited electronmicroscopically, such as glial fibrils, basal bodies, centrioles and 9 + 1 patterned cilia-like structures in 2 cases. These findings suggest that central neurocytoma is an embryonal tumor in the wide sense, originating from the germinal matrix cell of the lateral ventricles and possessing multipotency, with potent differentiation from mature neurons.
Sigma receptor involvement in the oxyntic mechanism of gastric parietal cells was investigated using isolated guinea pig parietal cells. Using the 14C-aminopyrine accumulation method, di(orthotolyl)guanidine (DTG), a sigma receptor agonist, demonstrated peak stimulation of acid production at a concentration of 5 x 10(-5) M. The DTG-induced stimulatory effect on 14C-aminopyrine accumulation in preparations enriched in parietal cells was inhibited by haloperidol, a DTG inhibitor, and omeprazole, a proton pump inhibitor, in a concentration-dependent manner. Assessment of the interaction between DTG and agonists for histamine, gastrin, and muscarine receptors demonstrated a potentiating interaction effect on acid production only when parietal cells were exposed to both DTG and histamine. A receptor-binding assay using 3H-DTG revealed two sigma receptor subtypes, sigma 1 and sigma 2, on the crude membranes of parietal cells. There was a direct relationship between DTG dose and intracellular Ca2+ concentration, but there was no change in intracellular cyclic adenosine 5'-monophosphate (cAMP) concentration when parietal cells were exposed to DTG. These results demonstrate that sigma receptors exist on guinea pig gastric parietal cells and suggest that they play a role in acid production via an increase in intracellular Ca2+ concentration.
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We analyzed the frequency of somatic mutation in immunoglobulin genes from hybridomas that secrete anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) monoclonal antibodies. A high frequency of mutation (3.3-4.4%) was observed in both the rearranged VH186.2 and V lambda 1 genes, indicating that somatic mutation occurs with similar frequency in these genes in spite of the absence of an intron enhancer in lambda 1 chain genes. In contrast to the high frequency in J-C introns, only two nucleotide substitutions occurred at positions -462 and -555 in the 5' noncoding region in one of the lambda 1-chain genes and in none of the other three so far studied. Since a similar low frequency of somatic mutation was observed in the 5' noncoding region of inactive lambda 2-chain genes rendered inactive because of incorrect rearrangement, this region may not be a target or alternatively, may be protected from the mutator system. We observed a low frequency of nucleotide substitution in unrearranged V lambda 1 genes (approximately 1/15 that of rearranged genes). Together with previous results (Azuma T., N. Motoyama, L. Fields, and D. Loh, 1993. Int. Immunol. 5:121), these findings suggest that the 5' noncoding region, which contains the promoter element, provides a signal for the somatic mutator system and that rearrangement, which brings the promoter into close proximity to the enhancer element, should increase mutation efficiency.