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Biomedical subjects

Y Koga

Publications and source records attributed to Y Koga.

At least 217 records · Page 12Linked to original sources

Indium-111 antimyosin monoclonal antibody Fab imaging in patients with cardiomyopathy.

Six patients with cardiomyopathy were imaged following intravenous injection of an indium-111 labeled monoclonal antibody directed against the heavy chain of cardiac myosin. Two patients had hypertrophic non-obstructive cardiomyopathy (HNCM), two patients had dilated cardiomyopathy (DCM), and two patients had specific heart muscle disease. One of 2 patients with HNCM and one of 2 patients with DCM had a positive antimyosin scan. The 2 patients with specific heart muscle disease manifested persistent blood pool activity of the antibody, thereby precluding interpretation of the images. The present report demonstrates that antimyosin antibody imaging may provide evidence of myocardial injury, or necrosis in some patients with cardiomyopathy.

Adolescent↗

Intrapleural perfusion hyperthermo-chemotherapy for malignant pleural dissemination and effusion.

Taking advantage of the antitumor effect of hyperthermia, we administered intrapleural perfusion hyperthermo-chemotherapy for the treatment of malignant pleural seeding or pleural effusion. This consists of irrigating the pleural space for 2 hours with 43 degrees C saline solution containing cis-platinum using specially devised extracorporeal circuits. From January 1988 through December 1993, we performed this technique in 12 patients with malignant disseminated lesions stemming from lung cancer who also underwent surgical resection of the primary lesions and in 7 patients with malignant pleural effusions who did not undergo thoracotomy or surgical resection. There were no serious clinical complications associated with this procedure. The pharmacokinetics showed that a high concentration of cis-platinum (more than 17.6 micrograms/mL in the free form) was retained in the pleural cavity during perfusion. After this therapy, the cancer cells showed marked degeneration with fibrosis in the pleural wall. The pleural effusion was well controlled in 100% of the patients. The median survival time in the 12 patients with pleural disseminated lesions who were treated with intrapleural perfusion hyperthermo-chemotherapy was 20 months. On the other hand, the median survival time in 7 patients with similar lesions who did not receive IPHC was only 6 months. Intrapleural perfusion hyperthermo-chemotherapy seems to have considerable value as an adjuvant therapy for patients with pleural dissemination who have had their primary lesions removed.

Adult↗

Management of intraaortic balloon entrapment.

Two cases of intraaortic balloon entrapment were presented. In patient 1, urokinase was injected into the gas driver lumen of the intraaortic balloon catheter, then it could be removed. In patient 2, the intraaortic balloon was removed retrogradely through the left axillary artery. If the entrapped intraaortic balloon is encountered, it is effective to try a clot-lysis method initially, followed by a surgical approach through a left axillary artery.

Aged↗

Disappearance of giant negative T waves in patients with the Japanese form of apical hypertrophy.

OBJECTIVES: The present study investigated the long-term changes in the electrocardiographic (ECG) hallmarks of the Japanese form of apical hypertrophy. BACKGROUND: Giant negative T waves and tall R waves in the left precordial leads are the ECG hallmarks of the Japanese form of apical hypertrophy. However, the long-term course is largely unknown. METHODS: Twenty-nine patients with apical hypertrophy (26 men, 3 women, mean age +/- SD 50.4 +/- 8.2 years) who showed left precordial giant negative T waves (< or = -10 mm) and tall R waves (> or = 26 mm) and spade configuration in the left ventriculogram were followed up for 10.9 +/- 3.7 years. RESULTS: The intermediate follow-up ECGs (5 to 9 years) showed disappearance of giant negative T waves in 31% and of tall R waves in lead V5 in 6%. At the long-term follow-up study (> or = 10 years), loss of giant negative T waves increased to 71%, with average T wave negativity in lead V4 or V5 decreasing from -16.5 +/- 5.1 to -6.9 +/- 4.2 mm. These T wave changes were associated with decreases in R wave amplitude in lead V5 from 40.7 +/- 9.6 to 26.1 +/- 13.8 mm, with loss of tall R waves in lead V5 in 38% of patients and development of abnormal Q waves in two patients. CONCLUSIONS: During the long-term follow-up of the Japanese form of apical hypertrophy, giant negative T waves disappeared in association with decreases in R wave amplitude in lead V5, indicating that these ECG hallmarks are clinical features that evolve progressively during the natural course of the disease.

Adult↗

DNA typing of HLA class II genes in Japanese patients with dilated cardiomyopathy.

HLA class II genes (DRB, DQA, DQB, DPA, and DPB) were typed at the DNA level using polymerase chain reaction/sequence-specific oligonucleotide probe analysis in 78 unrelated patients with DCM and 336 unrelated healthy controls to elucidate the HLA alleles or HLA haplotypes associated with DCM. The frequencies of DRB1*1401 (15.4% v 4.5%, RR = 3.90, P < 0.0005, Pc < 0.03), DQB1*0503 (14.1% v 5.4%, RR = 2.93, P < 0.007) and DRB1*1401-DQB1*0503 haplotype (11.5% v 1.5%, RR = 8.24, P < 0.00001, Pc < 0.01) were increased in the DCM patients. The frequency of HLA-DRB1*1101 (9.0% v 3.0%, RR = 3.26, P < 0.02) also was increased in the patients. In addition, the frequencies of DQB1*0604 and DPB1*0401 were increased in the DRB1*1401 and DRB1*1101 negative patients. In contrast, the frequencies of DQB1*0303 (19.2% v 30.7%, RR = 0.55, P < 0.05) and DRB1*0901-DQB1*0303 haplotype (16.7% v 29.8%, RR = 0.49, P < 0.02) were decreased in the DCM group. Disease susceptibility to DCM in the Japanese population, thus, may be controlled in part by a gene (or genes) in close linkage disequilibrium with DRB1*1401-DQB1*0503, DRB1*1101-DQB1*0301, and DQB1*0604-DPB1*0401 haplotypes, while the resistance to DCM may be associated with the DRB1*0901-DQB1*0303 haplotype.

Adolescent↗

sn-glycerol-1-phosphate dehydrogenase in Methanobacterium thermoautotrophicum: key enzyme in biosynthesis of the enantiomeric glycerophosphate backbone of ether phospholipids of archaebacteria.

One of the most characteristic features of archaebacterial ether phospholipids is the enantiomeric configuration of their glycerophosphate backbone (sn-glycerol-1-phosphate), that is the mirror image of the structure of the eubacterial or eukaryotic counterpart. The enzyme that forms glycerophosphate of this configuration was found for the first time in a cell-free extract of the methanogen, Methanobacterium thermoautotrophicum, and was identified as sn-glycerol-1-phosphate:NAD+ oxidoreductase (sn-glycerol-1-phosphate dehydrogenase) after partial purification. Because sn-glycerol-1-phosphate has been found to be a precursor of ether lipids of this organism, sn-glycerol-1-phosphate dehydrogenase is a key enzyme in the biosynthesis of the enantiomeric ether lipids of methanogens.

Animals↗

Calcium requirement and inhibitor spectrum for intracellular HIV type 1 gp160 processing in cultured HeLa cells and CD4+ lymphocytes: similarity to those of viral envelope glycoprotein maturase.

We recently purified the calcium-independent processing protease named viral envelope glycoprotein maturase (VEM), that converts human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein precursor gp160 to gp120 and gp41, from the human CD4+ T cell line, Molt-4 clone 8 [Kido, H., Kamoshita, K., Fukutomi, A., and Katunuma, N. (1993) J. Biol. Chem. 268, 13406-13413]. In this report, we deal with the inhibitor specificity and calcium requirement for intracellular gp160 processing in cultured HeLa cells and human CD4+ lymphocytes. Processing of gp160 in these cells infected with recombinant vaccinia virus encoding the gp160 gene was not affected by intracellular calcium depletion induced by the calcium ionophore A23187 and EGTA or by intracellular calcium administration. Processing of gp160 by the purified VEM in vitro was not inhibited by EDTA, EGTA, or the metallo-protease inhibitor phosphoramidon, but was specifically inhibited by a substrate analog, decanoyl-RVKR-chloromethylketone, and the trypsin-type protease inhibitors aprotinin, HI-30, and diisopropyl fluorophosphate (DFP). It was also inhibited by E-64 and thiol reagents. But intracellular gp160 processing was inhibited only by permeable, low molecular mass inhibitors of VEM, such as DFP, E-64, and thiol reagents. Syncytium formation induced by cell surface gp120 was also inhibited by permeable inhibitors of VEM. Taken together, our results indicate that calcium ions may not be essential for intracellular gp160 processing and so HIV-1 gp160 induced by recombinant vaccinia virus may be processed mainly by a protease(s) that does not require calcium ions, such as VEM in these cells.

Amino Acid Sequence↗

Effect on neonatal thyroid function of povidone-iodine used on mothers during perinatal period.

OBJECTIVE: Our objective was to evaluate the effect on the neonatal thyroid function of povidone-iodine (PVP-I) used on mothers during the perinatal period. METHODS: Eight consecutive-term pregnant women were randomly separated into 4 groups. Either PVP-1 or benzethonium chloride (BC) was used to disinfect both maternal skin during labor and vaginal lacerations after delivery in Group I and IV; and PVP-1 or BC was supplied to either skin or lacerations in Groups II and III. On day 5, we measured the iodide concentration in breast milk and random urine of neonates, and the levels of neonatal thyroid-stimulating hormone (TSH) and free thyroxine. RESULTS: The TSH levels in Group I and the breast-milk iodide concentrations in Groups I and II were significantly higher than those in Group IV (p < 0.05). Dietary iodide intake from breast milk correlated significantly with urinary iodide concentrations (r = 0.52, p < 0.001). In our clinic, the recall rate at the time of screening for congenital hypothyroidism was significantly decreased by discontinuing the use of PVP-I (4.47% vs 0.74%, p < 0.001). CONCLUSIONS: These findings suggest that the use of PVP-I on mothers is associated with transient neonatal hyperthyrotropinemia, in which breast milk might play an important role. Therefore, we recommend that the use of PVP-I be avoided during labor.

Anti-Infective Agents, Local↗

Granulation in livers of mice infected with Salmonella typhimurium is caused by superoxide released from host phagocytes.

The pathophysiological roles of superoxide (O2.-) at the site of infection of facultative intracellular bacteria were examined in this study. To evaluate the actual in vivo generation of the superoxide, an ex vivo chemiluminescence assay was newly developed. When ICR mice were infected with a sublethal dose (8 x 10(4) CFU) of Salmonella typhimurium, the number of bacteria in the liver reached its peak at 5 days after infection (10(5.05) CFU/g of liver) and decreased thereafter. At 21 days after infection, the bacteria became undetectable. On the other hand, phorbol myristate 13-acetate-stimulated O2.- generation reached a maximum at 7 days after infection (mean photon count, 1,249 cps versus 28.8 cps before infection; n = 4) and decreased thereafter to a level similar to that before infection at 21 days after infection (28.8 cps). Histological examinations revealed that the total area of the lesions reached a peak at 7 days after infection (7.2 x 10(4) microns 2/10 visual fields). In the early phase, a microabscess with infiltration of polymorphonuclear cells was noted, and then, in the late stage, the lesion was replaced by granulation with mononuclear cell infiltration. When microscopic lesions were measured histologically, a significant correlation between the area of the lesions and phorbol myristate 13-acetate-stimulated O2.- generation was observed, which suggested that superoxide was responsible for the generation of the lesions. Modified superoxide dismutase, i.e., alpha-4-([6-(N-maleimido)hexanoyloxymethyl] cumyl)half-butyl-esterified poly(stylrene-co-malelic acid)-conjugated superoxide dismutase (SM-SOD), was then applied. When SM-SOD was administered to suppress the O2.- generation in vivo, the number of bacteria increased (10(6.1) CFU). However, the lesion formation was inhibited (total lesion area, 0.3 x 10(4) microns 2). These results suggest that the establishment of the microabscess and granuloma formation after S. typhimurium infection is not due to the bacteria per se but rather to the O2.- from the host's phagocytes. Two aspects of the O2.-, i.e., the bactericidal role and the tissue-injurious effect, were clearly demonstrated in this study. Therefore, the information obtained from these results is useful in designing treatment strategy for similar kinds of infection.

Animals↗

In vitro analysis of mutations causing myoclonus epilepsy with ragged-red fibers in the mitochondrial tRNA(Lys)gene: two genotypes produce similar phenotypes.

Cytoplasts from patients with myoclonus epilepsy with ragged-red fibers harboring a pathogenic point mutation at either nucleotide 8344 or 8356 in the human mitochondrial tRNA(Lys) gene were fused with human cells lacking endogenous mitochondrial DNA (mtDNA). For each mutation, cytoplasmic hybrid (cybrid) cell lines containing 0 or 100% mutated mtDNAs were isolated and their genetic, biochemical, and morphological characteristics were examined. Both mutations resulted in the same biochemical and molecular genetic phenotypes. Specifically, cybrids containing 100% mutated mtDNAs, but not those containing the corresponding wild-type mtDNAs, exhibited severe defects in respiratory chain activity, in the rates of protein synthesis, and in the steady-state levels of mitochondrial translation products. In addition, aberrant mitochondrial translation products were detected with both mutations. No significant alterations were observed in the processing of polycistronic RNA precursor transcripts derived from the region containing the tRNA(Lys) gene. These results demonstrate that two different mtDNA mutations in tRNA(Lys), both associated with the same mitochondrial disorder, result in fundamentally identical defects at the cellular level and strongly suggest that specific protein synthesis abnormalities contribute to the pathogenesis of myoclonus epilepsy with ragged-red fibers.

Cell Line↗

Unresectable hepatocellular carcinoma: analysis of prognostic factors in transcatheter management.

PURPOSE: To evaluate the effect of transcatheter management of hepatocellular carcinoma (HCC) on survival. MATERIALS AND METHODS: A prospective trial of transcatheter arterial embolization (TAE) was performed in patients with unresectable HCC. Three hundred twenty-two patients (265 men, 57 women; age range, 30-83 years) underwent TAE alone: 60 patients underwent TAE with gelatin sponge (GS) that contained anticancer agents (protocol 1); 78, TAE with GS and iodized oil mixed with anticancer agents (protocol 2); and 159, TAE with iodized oil with anticancer agents (protocol 3). A Cox proportional hazard model was used to analyze prognostic factors. RESULTS: In the randomized group (n = 272), survival rates for protocols 1, 2, and 3 were 80.4%, 86.3%, and 65.9%, respectively, at 1 year. Findings of analysis of prognostic factors showed that extrahepatic metastases, ascites, tumor extension, and icterus were the important factors. CONCLUSION: TAE with GS was superior to TAE without GS. Patient characteristics were important factors for survival.

Adult↗

Synthesis of 2(1H)-quinolinone derivatives and their inhibitory activity on the release of 12(S)-hydroxyeicosatetraenoic acid (12-HETE) from platelets.

A search for potent inhibitors of release of 12(S)-hydroxyeicosatetraenoic acid (12-HETE), which plays an important role in the pathogenesis of various circulatory disorders and arteriosclerosis, led us to 6-[4-(1-cyclohexyl-5-tetrazolyl)butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) and 2(1H)-quinolinone derivatives having an azole group in the side chain. Many 2(1H)-quinolinone derivatives were synthesized and tested in vitro for the inhibitory activity in human platelets. 3,4-Dihydro-6-[3-(1-o-tolylimidazol-2-yl)sulfinylpropoxy]-2( 1H)-quinolinone (5k) was found to be one of the most potent inhibitors of 12-HETE release, being more potent than esculetin. In addition, the sulfoxide 5k showed in vivo inhibitory activity on platelet adhesion in rats. Since 5k is racemic, the enantiomers were prepared and their potencies were compared in vitro and in vivo. (S)-(+)-5k had the best pharmacological profile and was selected as a candidate drug for further development. The structure-activity relationships are discussed.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

The seven countries study in Japan. Twenty-five-year experience in cardiovascular and all-causes deaths.

Within the Seven Countries Study two Japanese cohorts of men aged 40-59 were enrolled, one from the farming village of Tanushimaru (n = 508) and the other from the fishing village of Ushibuka (n = 502), both located in Kyushu. Cardiovascular risk factors were measured at entry and 10 years later in the survivors. The 25-year death rate for all causes was 30% higher in Ushibuka than in Tanushimaru (p < 0.001) and higher also from specific causes except for violence. Baseline differences in the levels of age, blood pressure, serum cholesterol, smoking habits, body mass index and heart rate explained only 19% of the difference in all-cause mortality between the two towns. Multivariate models from data of the pooled cohorts showed that age was a significant predictor of coronary heart disease, stroke, cancer, all other causes and all-cause mortality. Cigarette smoking predicted coronary heart disease, cancer and all-cause mortality. Systolic blood pressure predicted coronary heart disease, stroke and all-cause mortality. Serum cholesterol, body mass index and heart rate predicted none of these five causes of death. Changes in systolic blood pressure during the first 10 years of follow-up were directly related to deaths between 10 and 25 years of follow-up, significantly improving the predictive power of the multivariate model. Changes in the other risk factors did not contribute, however, to improved prediction.

Adult↗

[A technique for removal of entrapped intra-aortic balloon catheter through the left axillary artery].

A case of intra-aortic balloon pumping (IABP) entrapment in which the ruptured catheter could be removed through the left axillary artery was reported. A 68-year-old man was admitted with persistent chest pain, and because of his poor cardiac condition, an IAB catheter was inserted by the Seldinger technique. During attempted extraction of the IAB catheter resistance was encountered and it turned out to be entrapped. Then a guide-wire was passed through the IAB lumen to the left axillary artery, the artery was exposed, and the tip of the guide-wire and IAB catheter were led to the arteriotomy site. After the balloon was dissected, the IAB catheter could be removed through the axillary artery. Finally, left femoro-left branchial artery bypass was performed with e-PTFE graft because of the arterial injury and ischemia of the involved arm. The patient recovered from this episode.

Aged↗

[Analysis of relationship between personality and emesis gravidarum in pregnant women].

The relationship between personality types and the symptoms of emesis gravidarum in pregnant women was analyzed by means of the Cattel personality test (revised by Nishizono) performed in early and mid pregnancy. Personality types were classified into five from cyclothymia A to schizothymia E. As for emesis, the patients were also classified into three groups, severe (35), mild (41) and none (19), according to the severity and duration of the symptoms. As a result, there was no significant difference between the types and the symptoms, but significant differences were seen in interpersonal attitudes, especially in sociality and dominative propensity, which were constituents of the personality type. The results of the analysis suggested that the patients who revealed disunification tended to express strong emesis as a somatic language. These results therefore indicate the necessity for counseling about personality without simply explaining it as their predisposing constitution, when we encounter strongly emetic pregnant women.

Female↗