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Biomedical subjects

H Minami

Publications and source records attributed to H Minami.

At least 127 records · Page 7Linked to original sources

Clinical and pharmacologic analysis of hyperfractionated daily oral etoposide.

PURPOSE: The antitumor effect of etoposide is increased by maintaining a low blood level, whereas high peak levels may cause myelotoxicity. We investigated whether a constant low blood level could be obtained by the administration of oral etoposide three times daily. PATIENTS AND METHODS: Nineteen patients with non-small-cell lung cancer were treated with oral etoposide (25 mg three times daily for 21 days) as monotherapy or in combination with cisplatin 80 mg/m2. A pharmacokinetic model that predicted the mean blood concentration (Cmean) was developed in the 10 patients on etoposide monotherapy and validated in the nine patients on combination chemotherapy. Pharmacodynamic relationships were evaluated in each group. RESULTS: Etoposide dose per body-surface area ranged from 45 to 63 mg/m2/d (median, 53), but did not correlate with plasma level. Cmean was 1.1 +/- 0.3 micrograms/mL. Peak concentrations ranged from 0.6 to 2.5 micrograms/mL. The intrapatient coefficient of variation for plasma etoposide concentrations was 22% +/- 10%. Cmean was accurately estimated as follows: Cmean = 0.098 + 0.413 x C0 + 0.458 x C2 (r = .97, P = .0001), where C0 and C2 represent concentrations before and 2 hours after administration. This model was unbiased (mean predictive error [MPE], 0.0 microgram/mL) and precise (root mean square error [RMSE], 0.1 microgram/mL). Leukopenia was the major toxicity. The surviving fraction of leukocytes (SF; nadir count/pretreatment count) was correlated to Cmean as follows: SF = 0.87 - 0.34 x Cmean (r = .67, P = .03) in the monotherapy group and SF = 0.64 - 0.33 x Cmean (R = .77, P = .03) in the combination chemotherapy group. Two and four patients treated with monotherapy and combination chemotherapy showed responses, respectively. All responders had a Cmean > or = 1.0 microgram/mL. CONCLUSION: Hyperfractionated oral etoposide achieveda stable plasma level that could be predicted by measurement at only two times.

Administration, Oral↗

Occult thymic carcinoma presenting as malignant cardiac tamponade.

A 66-year-old woman who presented with malignant cardiac tamponade of unknown origin was eventually found to have a tiny squamous cell carcinoma of the thymus. Thus, even a small thymic carcinoma can exhibit highly aggressive behavior. It should be included in the differential diagnosis of malignant cardiac tamponade of unknown origin.

Aged↗

Activation of ornithine decarboxylase in epithelial cells of rat intestine.

Intestinal ornithine decarboxylase (ODC) is strongly induced by dietary amino acid and protein feeding. However, the consequence of this induction is unknown. In this study, we analyzed the relationship between intestinal ODC activity and DNA synthesis in villus and crypt cells of rat intestine. Single amino acid diets and protein diets stimulated ODC activity in villus cells, but not in crypt cells. However a 20% casein diet induced ODC activity and increased the putrescine concentration in villus and crypt cells. Administration of alpha-difluoromethylornithine, a suicide inhibitor of ODC, prevented both an increase in putrescine level and DNA synthesis in the crypt cells. Observations suggested that the induction of ODC is necessary to initiate DNA synthesis in rat intestinal epithelium.

Animals↗

[Myocardial structural proteins in cor pulmonale. Analysis by two-dimensional electrophoresis].

Changes in cardiac structural proteins caused by cor pulmonale were studied with two-dimensional electrophoresis. Sprague-Dawley rats were exposed to an oxygen-poor gas mixture (10% O2/90% N2) for three weeks. These rats (the hypoxic group) were compared to a control group that was kept in room air. Hemoglobin, hematocrit, and right ventricular systolic pressure were greater in the hypoxic group than in the control group. After the third week, desmin content of both ventricular muscles had increased in the hypoxic group, and was significantly greater in the hypoxic group than in the control group. The contents of other cardiac structural proteins did not change. These data suggest that increases in desmin are caused by adaptation of the myocardium to pressure overload associated with pulmonary hypertension. However, increases in the desmin content of the left ventricular muscle might be caused by volume overload, humoral factors, or might be a direct effect of hypoxemia.

Animals↗

[A case of rhabdomyolysis complicated with myocardial injury].

A 22-year-old man developed transient unconsciousness during running. He developed fever, nausea, vomiting, diarrhea and general fatigue. Next day, he was admitted to National Hospital Nayoro because of high serum CK level of 13,610U/l. Biochemical analyses revealed elevated serum myoglobin, increased CK-MM isozyme, aldolase and lactate dehydrogenase, increased serum osmolality, increased uric acid, and decreased serum potassium levels. Therefore, he was diagnosed as having rhabdomyolysis. In addition, serum CK-MB isozyme, cardiac myosin light chain I and troponin T were increased, suggesting the damage of cardiac muscle. Electrocardiogram showed elevated ST segment and inverted T on V2-4, which were not observed previously. He had no preceding infectious disease, drug ingestion or an underlying metabolic disorder. The rhabdomyolysis may be precipitated by the superimposition of dehydration and loss of potassium due to diarrhea and vomiting. The myocardial injury, probably produced by transient myocardial ischemia, should be paid attention in case of rhabdomyolysis.

Adult↗

Vitamin D-dependent rickets type II: regulation of human osteocalcin gene expression in cells with defective vitamin D receptors by 1,25-dihydroxyvitamin D-3, retinoic acid, and triiodothyronine.

The vitamin D receptor (VDR) is a nuclear transcription factor which binds to the vitamin D response element (VDRE) of the human osteocalcin gene and regulates its expression. Humans with VDR gene mutations, ever among those with the same point mutation in their VDR gene, demonstrate clinical heterogeneity. In addition, in some patients with these mutations, rickets has not recurred following cessation of therapy during follow-up ranging from 6 to 24 years. While important, it is likely that the VDR protein is not the sole factor in the development of rickets. To try to understand these clinical findings, the complex formed between the VDRE and one or more proteins in the nuclear extracts of cultured skin fibroblasts treated with 1,25-dihydroxyvitamin D-3 (1,25(OH)2D3), retinoic acid (RA), and/or triiodothyronine (T3) was investigated since such complexes are likely to precede the transcription of the VDR gene. Complex formation in the control cells with an intact VDR was increased by treatment with either 0.1 nM, 1 nM, 10 nM 1,25(OH)2D3, 100 nM RA, or 100 nM T3; however, combinations of these compounds did not produce an additive effect. In cells of affected patients, 1,25(OH)2D3, RA, or T3 increased complex formation, while no combination had an additive effect. These results indicate that 1,25(OH)2D3, RA, and T3 play a role in the regulation of bone remodeling through modulating the formation of protein complexes on the VDRE. Therefore, the clinical observations in patients with a VDR mutation might be explained at least in part by the overlapping control of osteocalcin expression by 1,25(OH)2D3, RA and T3.

Base Sequence↗

Characterization of the rabbit intestinal fructose transporter (GLUT5).

Recent studies suggest that the jejunal/kidney-type facilitative glucose transporter (GLUT5) functions as a high-affinity D-fructose transporter. However, its precise role in the small intestine is not clear. In an attempt to identify the fructose transporter in the small intestine, we measured fructose uptake in Xenopus oocytes expressing jejunal mRNA from five species (rat, mouse, rabbit, hamster and guinea-pig). Only jejunal mRNA from the rabbit significantly increased fructose uptake. We also cloned a rabbit GLUT5 cDNA from a jejunal library The predicted amino acid sequence of the 487-residue rabbit GLUT5 showed 72.3 and 67.1% identity with human and rat GLUT5 respectively. Northern-blot analysis revealed GLUT5 transcripts in rabbit duodenum, jejunum and, to a lesser extent, kidney. After separation of rabbit jejunal mRNA on a sucrose density gradient, the fractions that conferred D-fructose transport activity in oocytes also hybridized with rabbit GLUT5 cDNA. Hybrid depletion of jejunal mRNA with a GLUT5 antisense oligonucleotide markedly inhibited the mRNA-induced fructose uptake in oocytes. Immunoblot analysis indicated that GLUT5 (49 kDa) is located in the brush-border membrane of rabbit intestinal epithelial cells. Xenopus oocytes injected with rabbit GLUT5 cRNA exhibited fructose uptake activity with a Km of 11 mM for D-fructose. D-Fructose transport by GLUT5 was significantly inhibited by D-glucose and D-galactose. D-Fructose uptake in brush-border membrane vesicles shows a Km similar to that of GLUT5, but was not inhibited by D-glucose or D-galactose. Finally, cytochalasin B photolabelled a 49 kDa protein in rabbit brush-border-membrane preparations that was immunoprecipitated by antibodies to GLUT5. Our results suggest that GLUT5 functions as a fructose transporter in rabbit small intestine. However, biochemical properties of fructose transport in Xenopus oocytes injected with GLUT5 cRNA differed from those in rabbit jejunal vesicles.

Amino Acid Sequence↗

The effect of KN-62, Ca2+/calmodulin dependent protein kinase II inhibitor on cell cycle.

The isoquinolinesulfonamide derivative, KN-62, is a potent and specific inhibitor of Ca2+/calmodulin dependent protein kinase II (CaM kinase II) (Tokumitsu, H., Chijiwa, T., Hagiwara, M., Mizutani, A., Terasawa, M., and Hidaka, H.(1990) J. Biol. Chem. 265, 4315-4320). KN-62 inhibits growth of K562 cells, in a dose-dependent manner. Flow cytometric analysis demonstrates that the treatment of K562 cells with 10 microM KN-62 causes an accumulation of cells in S phase. Immunoblotting studies showed that specific antibodies against CaM kinase II recognized the 65 kDa of protein in K562 cells. This protein showed protein kinase activity as examined by the activity gel method. The inhibition of this enzyme activity by KN-62 was dose-dependent. The immunoprecipitates with the antibodies from K562 cells phosphorylates the synthetic peptide substrates, syntide-2. These results suggest that CaM kinase II plays an important role in the mechanisms for the cell growth in K562 cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Different effects of antidepressants on dissociation of 3H-imipramine from solubilized binding sites of rat brain.

1. The effects of several antidepressants and 5-hydroxytryptamine on dissociation of 3H-imipramine from solubilized binding sites were investigated. 2. Binding sites were solubilized from rat brain membranes and gelfiltrated on a column of Sephacryl S-300. 3. Most of the agents used allowed biphasic dissociation with 1mM of displacing agent and without using dilution-induced dissociation. This biphasic dissociation without nonspecific effects of membranes may be due to the existence of low-affinity binding sites. 4. Dissociation of up to 40 min followed first-order kinetics. The dissociation half-life of 3H-imipramine with the various displacing agents was calculated at from 15.0 to 25.0 min, and the differences among the agents were not so significant as the attenuation or the acceleration of the dissociation was indicated. The lower concentration of the displacing agents may obscure the modulation of the dissociation.

Animals↗

Severe neurological abnormalities associated with a mutation in the zinc-finger domain in a group A xeroderma pigmentosum patient.

All the reported Japanese patients with group A xeroderma pigmentosum (XP) have two or three mutations at codon 116 in exon 3, codon 228 in exon 6, and the splicing acceptor site of intron 3 of XP group A complementing (XPAC) gene. A homozygote (XP39OS) with a nonsense mutation at codon 228 has less severe neurological abnormalities than patients with the splicing mutation at the acceptor site of intron 3. As homozygotes for the nonsense mutation at codon 116, which truncates a carboxyl-terminal site of XPAC protein at an early part of its zinc-finger domain, have not been reported previously, the possible severity of associated neurological abnormalities was not known. We report a group A XP patient, XP18OS, who had neurological abnormalities which were more severe than those in patients homozygous for the splicing mutation. The polymerase chain reaction product from exon 3 of the patient's XPAC gene was digested completely into three fragments by MseI restriction endonuclease. Thus, the patient was homozygous for the mutation at codon 116.

Base Sequence↗

Endobronchial mucosal bridges as evidence of residual malignancy.

Three patients who exhibited endobronchial mucosal bridges that formed at the site of tumor regression following chemotherapy for small cell lung carcinoma are presented. Histopathologic examination showed residual malignant cells in 2 of the 3 patients within the submucosal fibrous tissue and an overlying benign epithelium. Although these mucosal bridges were previously thought to represent a complete remission following chemotherapy or radiotherapy for small cell lung carcinoma, they may, in fact, harbor a residual malignancy under the benign mucosa.

Aged↗

Interbronchoscopist variability in the diagnosis of lung cancer by flexible bronchoscopy.

STUDY OBJECTIVE: We evaluated the interbronchoscopist variability in the diagnosis of lung cancer by flexible bronchoscopy. DESIGN AND SETTING: A retrospective review of the bronchoscopic records and clinical charts of patients at a university-affiliated hospital. PATIENTS AND MEASUREMENTS: All records of flexible bronchoscopic procedures performed for the diagnosis of lung cancer were retrospectively reviewed, and procedures that obtained histologic or cytologic evidence of malignancy were considered positive. Rates of positivity were compared according to the following factors: operator, operator experience, bronchoscopic findings, tumor location, and tumor laterality. Factors that affected the positivity rate were evaluated using logistic regression analysis. RESULTS: Of 384 bronchoscopic procedures performed in 353 patients, 275 (72 percent) were positive. The positivity rate differed significantly depending on the operator (p = 0.003) and the bronchoscopic findings (p < 0.001). A difference between operators was noted in technically difficult cases without epithelial or subepithelial findings and when tumors were located in the upper lobe or the superior segment of the lower lobe. The bronchoscopic findings and the operator also emerged as factors significantly affecting the positivity rate in the logistic analysis. CONCLUSIONS: The diagnostic yield of bronchoscopy for lung cancer is dependent on both the type of bronchial lesion present and the bronchoscopist.

Bronchoscopy↗

Rupture of thoracic aorta caused by penetrating aortic ulcer.

We present the findings in a 57-year-old man with a rupture of the thoracic aorta that originated in a penetrating atherosclerotic aortic ulcer. It formed a large hematoma that clinically mimicked a true saccular thoracic aneurysm. The possibility of penetrating aortic ulcer should be considered in the differential diagnosis of aortic aneurysm.

Aortic Aneurysm, Thoracic↗

[Clinical evaluation of intracavernous self-injection of vasoactive drugs for impotence: a long-term follow-up observation].

From December 1989 to September 1992, nine patients with impotence were instructed to perform intracavernous self-injection of vasoactive drugs. At first 40 mg of papaverine hydrochloride was used in all patients and the response on erection was evaluated. If the response did not show sufficiently functional erection, a mixture of 40 mg of papaverine hydrochloride and 1 mg of phentolamine mesylate or 20 mg of prostaglandin E1 was reinjected. Eight patients had achieved full erections and vaginal penetrations without noteworthy complications during the follow-up period. Out of eight patients, three patients were able to ejaculate and one patient showed recovery of erection. No major side effects were seen. In conclusion, intracavernous self-injection is a useful modality for impotence.

Adult↗

[A case of mediastinal mature teratoma presenting increased serum CA19-9 level].

A case of mediastinal mature teratoma with elevated serum CA19-9 level is reported. A 50-year-old woman admitted to our hospital complaining of cough and chest pain. Chest X-ray showed an abnormal mass shadow with retention of the right pleural effusion. Her serum CA19-9 level was high (204.4 U/ml), while serum AFP, CEA, HCG levels were normal. On lateral thoracotomy, an anterior mediastinal tumor perforating into the right lung was revealed and the total resection of the tumor with adherent part of the right lung was performed. Postoperatively, her serum CA19-9 level returned to normal. Histological examination disclosed a mature teratoma consisting of skin, pancreatic tissue, cartilage, bronchial epithelium, etc. Immunohistochemical staining were positive in the bronchial epithelium and bronchial gland but was negative in the pancreatic tissue of the tumor. This is a rare case of mediastinal mature teratoma with elevated serum CA19-9 level and negative immunohistochemical staining for it in the pancreatic tissue of the tumor.

CA-19-9 Antigen↗