Biomedical subjects

H Kinoshita

Publications and source records attributed to H Kinoshita.

At least 19 recordsLinked to original sources

PubMed1995

Expression of immunoreactive human hepatocyte growth factor in human esophageal squamous cell carcinomas.

Hepatocyte growth factor (HGF) is a potent mitogen for epithelial cells that promotes cell motility and invasiveness. In this study, we report that the human esophageal squamous cell carcinoma (SCC) shows a significant elevation of HGF concentration (600 +/- 416 ng/100 mg protein), compared to normal mucosa (80 +/- 183 ng/100 mg protein) (P < 0.01). An association could be established between levels of HGF and decreasing differentiation of 37 SCCs. The 2-year crude survival rates were 51.1% and 68.4% at high and low HGF concentrations, respectively. The results indicate that HGF is significantly increased in human esophageal SCCs, especially of poorly differentiated type. HGF might thus be useful as a biological biomarker for characterization of human esophageal SCCs.

Adult↗

PubMed1995

Polyamine metabolism in the rat liver after orthotopic liver transplantation.

We examined the polyamine metabolism in liver transplanted after cold ischemia and effects of putrescine administration on liver injury, liver regeneration, and survival rate after orthotopic liver transplantation in the rat. Male Wistar rats were used as donors and recipients. Grafts were stored in Euro-Collins solution for 6 h at 4 degrees C. Orthotopic liver transplantation was performed by the three cuff technique. The activities of aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase elevated and peaked 4 h after liver transplantation. Hepatic ornithine decarboxylase and spermidine/spermine N1-acetyltransferase activities were also elevated and peaked 8 h after the operation. In agreement with the increases in ornithine decarboxylase and spermidine/spermine N1-acetyltransferase activities, the putrescine content increased and spermidine content decreased in the transplanted liver. Putrescine administrated intraperitoneally improved the survival rate, decreased serum transaminase level and increased the [3H]thymidine incorporation into the liver DNA. These findings suggest that both biosynthetic and biodegradative pathways are stimulated in liver transplantation, resulting in the increase in the formation of putrescine from ornithine and from spermidine, and that putrescine administration improve the survival rate by protecting the damaged graft after cold ischemia and reperfusion and by stimulating liver regeneration.

Acetyltransferases↗

PubMed1995

Selective separation of human peripheral platelets, granulocytes and lymphocytes by surface affinity chromatography.

Selective separation of human peripheral platelets, granulocytes and lymphocytes was investigated by column liquid chromatography using methoxyethoxymethyl (MEM) bonded-phase columns (25 x 0.9 cm I.D.). Isotonic solutions containing mono- and disaccharides, methyl-alpha-D-pyranosides and a physiological saline at pH 7.4 were used as the mobile phase. Granulocytes and lymphocytes were separated on the MEM-Cellulofine GH-25 column by elution with 0.3 M D-mannose solution. The isolation of platelets and lymphocytes from human leukocyte-rich plasma was performed with a MEM-Sephadex G25 column and elution with 0.27 M sucrose solution. On the same column platelets could also be collected selectively by elution with 0.31 M methyl-alpha-D-mannoside at the high recovery of 100%. The isolated cells were viable for more than 90%.

Blood Platelets↗

PubMed1995

Development of human precision grip. IV. Tactile adaptation of isometric finger forces to the frictional condition.

The adaptation of the grip forces to the frictional condition between the digits and an object relies on feedforward sensorimotor mechanisms that use tactile afferent input to intermittently update a sensorimotor memory that controls the force coordination, i.e., the ratio between grip force (normal to the grip surface) and load force (tangential to the grip surface). The present study addressed the development of these mechanisms. Eighty-nine children and 15 adults lifted an instrumented object with exchangeable grip surfaces measuring the grip and load forces. Particularly in trials with high friction (sandpaper), the youngest children used a high grip force to load force ratio. Although this large safety margin against slips indicated an immature capacity to adapt to the frictional condition, higher grip forces were produced for more slippery material (silk versus sandpaper). The safety margin decreased during the first 5 years of age, in parallel with a lower variability in the grip force and a better adaptation to the current frictional condition. The youngest children (18 months) could adapt the grip force to load force ratio to the frictional condition in a series of lifts when the same surface structure was presented in blocks of trials, but failed when the surface structure was unpredictably changed between subsequent lifts. The need for repetitive presentation suggests a poor capacity to form a sensorimotor memory representation of the friction or an immature capacity to control the employed ratio from this representation. The memory effects, reflected by the influences of the frictional condition in the previous trial, gradually increased with age. Older children required a few lifts and adults only one lift to update their force coordination to a new friction. Hence, the present finding suggests that young children use excessive grip force, a strategy to avoid frictional slips, to compensate for an immature tactile control of the precision grip.

Adolescent↗

PubMed1995

Position of the sulfhydryl group and the disulfide bonds of human glucocerebrosidase.

Purified human glucocerebrosidase isolated from placenta was modified with [14C]-iodoacetic acid without reduction and digested with both protease-V8 at pH 4.0 followed by alpha-chymotrypsin at pH 7.5. The majority of radioactivity was found in a peptide that contained the [14C]-carboxymethylated-cysteine identified as CM-Cys18. Direct sequencing of the N-terminus of the intact labeled protein confirmed the modification of Cys18. For identification of disulfide bond-containing peptides, another portion of glucocerebrosidase was alkylated with nonlabeled iodoacetic acid and then digested with protease V8 and alpha-chymotrypsin as before. Twenty-eight HPLC fragments were collected. These purified peaks were then reduced with beta-mercaptoethanol followed by S-carboxymethylation with [14C]-iodoacetic acid. Three peptides among these 28 peptides generated two radioactive daughter peptides. These peptides were sequenced and the position of the radioactive CM-cysteines identified. The locations of these disulfides are Cys4-Cys16, Cys23-Cys342, and Cys126-Cys248. Attempts to reproduce the free sulfhydryl labeling experiments using the glucocerebrosidase isolated from Ceredase proved unsuccessful. No label was incorporated by this enzyme prior to reduction. This result suggests that the form of the protein used in the clinic differs from the native protein.

Amino Acid Sequence↗

PubMed1995

Arthroscopic repair for a flap tear of the posterior horn of the lateral meniscus adjacent to its tibial insertion.

A flap tear of the posterior horn of the lateral meniscus adjacent to its tibial insertion combined with acute rupture of the anterior cruciate ligament was successfully repaired arthroscopically by a combination of advancement of the tip of the flap into a drill hole created in the tibia and an inside-out stacked suture technique using Henning instrumentation in two cases. However, the long-term function of the repaired menisci, which was reduced several millimeters in circumferential length, is still unknown.

Adolescent↗

PubMed1995

Disparate circadian variations of blood pressure and body temperature in bedridden elderly patients with cerebral atrophy.

Twenty bedridden elderly patients with normal sleep-wake cycles were studied to evaluate the circadian variations of blood pressure, pulse rate, body core temperature, cortisol, and catecholamines with a focus on their relation to cerebral atrophy. Twenty-four-hour blood pressure (BP) and pulse rate monitorings were done with simultaneous measurement of urinary bladder temperature. Urine was also collected every 4 h to measure 17-hydroxycorticosterone and catecholamines. Based on the brain CT, frontal horn index (FHI: maximal distance between bilateral frontal horns/the corresponding width of the skull) was calculated as an index of cerebral atrophy. Analysis by the cosinor method revealed that the significant circadian rhythm with nocturnal decline was observed in only 9 patients (45%) for BP and in 13 patients (65%) for pulse rate. In contrast, 19 of 20 patients (95%) showed significant circadian rhythms of bladder temperature, with the nadirs appearing between 00:06 and 06:54. In the subgroup of mild cerebral atrophy (FHI < 0.30, n = 11), BP and pulse rate fell modestly but significantly during nighttime, whereas they did not fall in the subgroup of moderate to severe cerebral atrophy (FHI > or = 0.30, n = 9). The possibility could not be excluded that the sleep disturbance might result in the relatively high BP during nighttime. Bladder temperature, 17-hydroxycorticosteroids, and catecholamines showed significant nocturnal falls in both groups. In conclusion, nocturnal fall of BP disappeared in the bedridden elderly patients with cerebral atrophy, which cannot be explained by the change in the circadian variation of the sympathetic nervous system, cortisol, or body core temperature.

Aged↗

PubMed1995

Allelic frequency of p53 gene codon 72 polymorphism in urologic cancers.

Alterations in the p53 tumor suppressor gene appear to be important in the development of many human tumors. The wild-type p53 gene has a polymorphism at codon 72 that presents the arginine (CGC) or proline (CCC) genotype, which recently has been reported to be associated with genetically determined susceptibility to smoking-related lung cancers. To determine whether this p53 genotype influences individual risk of urologic cancer and/or its progression, we used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis to assay the allelic frequencies of this polymorphism in 85 renal cell carcinoma patients, 151 urothelial cancer patients, 33 testicular cancer patients, 28 prostatic cancer patients and 56 patients without neoplastic disease. The allelic distributions of the three genotypes (Arg/Arg, Arg/Pro, Pro/Pro) in patients with renal cell carcinoma (29.4%, 55.3%, 15.3%), urothelial cancers (45.7%, 39.7%, 14.6%), testicular cancer (45.4%, 48.5%, 6.1%) or prostate cancer (42.9%, 50.0%, 7.1%) did not differ significantly from those in the normal controls. However, Pro/Pro genotype in renal cell carcinoma and urothelial cancer (smoking-related cancers) was more frequent than that in prostate cancer and testicular cancer (smoking-unrelated cancers) with borderline significance (P = 0.0881). There was no particular correlation between frequency of the three genotypes and grade or stage of each type of tumor. The association of genetic predisposition to urologic cancers with p53 gene codon 72 polymorphism is not so clear as the previous study of Japanese lung cancer patients, but this polymorphism may play some role in urothelial cancers and renal cell carcinoma, in which smoking is an epidemiological risk factor.

Adult↗

PubMed1995

Contribution of chromosome 9p21-22 deletion to the progression of human renal cell carcinoma.

To investigate the possible role of genomic aberrations of chromosome 9p21-22 in the tumorigenesis of human renal cell carcinoma (RCC), 10 RCC cell lines, 55 primary RCCs and 5 metastatic lesions were studied by Southern blotting and polymerase chain reaction-based analysis. Nine of 10 RCC cell lines showed a homozygous deletion of MTSI/CDKN2/(p16), while only 1 in 55 primary tumors had this deletion. Loss of heterozygosity on 9p21-22 was observed in 5 of 10 informative primary RCCs from patients with metastasis, but in only 4 of 31 informative tumors (13%) without metastasis (P = 0.025). Futhermore, 3 of 5 metastatic tumors (60%) showed hemi- or homozygous deletion of MTSI/CDKN2. These results indicate that the 9p21-22 deletion may be a relatively late event in RCC tumorigenesis and could be associated with RCC metastasis.

Alleles↗

PubMed1995

The ultrastructure, kinetics and intralobular distribution of apoptotic hepatocytes after portal branch ligation with special reference to their relationship to necrotic hepatocytes.

Apoptosis was originally defined as shrinkage necrosis, as a distinct mode of cellular death from coagulative necrosis in the rat liver lobes after portal branch ligation. To reveal the functional role of the apoptosis of hepatocytes in the volume reduction and recovery of normal hepatic architecture in portal-deprived liver lobes, we ligated the portal vein branch supplying the left and median liver lobes in Wistar rats. The liver lobes were perfusion-fixed with glutaraldehyde solution via the proximal site of the ligated portion of the portal vein on Days 1, 2, 4, 7 and 14 after operation and examined light and electron microscopically. On Day 2 after ligation, massive necrosis of hepatocytes occurred in the central to intermediate zones of the liver lobule, and apoptotic hepatocytes were observed in the boundary region between necrotic and normal areas. Such necrotic area-associated apoptosis of hepatocytes was most frequent on Day 2, declining thereafter. The sequential changes of the cell organelles in apoptotic hepatocytes were distinct from those in necrotic hepatocytes. On Day 7, when necrotic areas had almost disappeared the apoptosis of hepatocytes occurred mostly between intact hepatocytes in the "combined hepatic cell cords" which included no obvious sinusoidal lumen between hepatic cell cords. Such necrotic area-nonassociated apoptosis began to increase in frequency on Day 4, reached a peak on Day 7 and was gone by Day 14, when normal hepatic architecture was recovered. The present study suggests that both necrotic area-associated and non-associated apoptosis of hepatocytes may be induced by mild ischemia and contribute in part to the volume reduction of ligated liver lobes. It further reveals that the necrotic area-non-associated apoptosis of hepatocytes plays a role in reconstructing the architecture of hepatic cell cords after necrotic hepatocytes have undergone dissolution in the liver lobule.

Animals↗

PubMed1995

Polymyositis associated with thymoma and the subsequent development of pure red cell aplasia.

A 53-year-old woman with polymyositis associated with thymoma subsequently developed pure red cell aplasia (PRCA). She was hospitalized because of fever and muscle weakness, and diagnosed as having polymyositis by muscle biopsy. Remarkable clinical improvement followed administration of prednisolone. Progressive anemia became evident, however, while prednisolone was being tapered. Erythroid aplasia and the presence of thymoma confirmed the diagnosis of PRCA. Further examinations revealed that cytotoxic T cells may play an important role in the pathogenesis of this case.

Cytotoxicity, Immunologic↗

PubMed1995

[A case of massive air embolism during cardiopulmonary bypass].

Massive air embolism during cardiopulmonary bypass is one of the most serious complications in open heart surgery. We report such an accident, which was managed by temporary retrograde perfusion through the superior vena cava. A 59-year-old woman with severe mitral stenosis underwent mitral valve replacement. Soon after the start of the bypass, a massive air embolism occurred, probably because a bend in the tubing caused the blood level in the oxygenator to fall. The pump was stopped immediately and the patient was placed in the deep Trendelenburg position. The pump circuit was primed rapidly with fluid and retrograde perfusion through the superior vena cava was done at a flow rate of 1.5 L/min for 5 min. After air return from the aortotomy was confirmed, the standard bypass procedure was resumed with hypothermia. When the accident was discovered, and until the end of the operation, deep anesthesia was induced with pentobarbital for protection of the brain. Mitral valve replacement and tricuspid annuoplasty were done in the usual way thereafter. Postoperatively, the patient had no neurologic sequelae except for transient generalized convulsions, and has returned to normal daily activities.

Cardiopulmonary Bypass↗

PubMed1995

[Experience in intra-hepatic-arterial chemotherapy and hepatic resection for metastatic colorectal cancer].

Out of 213 consecutive cases of colorectal cancer patients, 39 patients had liver metastasis (31 synchronous metastases and 8 metachronous metastases). One-and 3-year survivals of these patients with liver metastases were 46.5% and 30.1%, respectively. Twenty-four patients who were treated with intra-hepatic-arterial chemotherapy had better survival rates of 54.7% at 1 year, and 36.5% at 3 years than non-treated patients. Fifteen patients who underwent curative hepatic resection had better survival rates of 83.1% at 1 year, and 48.5% at 3 years than non-resected patients. Thirteen patients who underwent curative hepatic resection followed by intra-hepatic-arterial chemotherapy had good survival rates of 80.8% at 1 year, and 53.9% at 3 years. Seven patients who had multiple metastases to both lobes, were treated with intra-hepatic-arterial chemotherapy. These patients had a better survival rate of 22.9% at 1 year than non-treated patients.

Adenocarcinoma↗

PubMed1995

[Surgical repair of ventricular septal perforation following acute myocardial infarction in an 86-year-old man].

We reported on an 86-year-old man who underwent successful repair of ventricular septal perforation (VSP). He was admitted to our hospital with acute inferior myocardial infarction (MI). Color Doppler echocardiogram showed the VSP located in posterior ventricular septum and right heart catheterization revealed a Qp/Qs of 2.1. His hemodynamic condition worsened, necessitating initiation of intraaortic balloon pumping 11 days after the onset of MI. Surgical repair of the VSP was performed on that day. A posterior ventricular septal defect was repaired using the method advocated by Daggett: the ventricular septal defect was closed with a Teflon felt patch, and left ventricular free wall was closed with an artificial graft. The postoperative course was uneventful, and the patient is doing well at one year after operation. He was, to the best of our knowledge, the eldest patient to undergo successful operation for VSP in Japan.

Aged↗

PubMed1995

[The ethanol elimination pharmacokinetics--the effects of genotypes of ALDH2 and CYP2E1 on the ethanol metabolism].

The effect of CYP2E1 upon the blood ethanol level was investigated. Blood ethanol concentrations in 4 volunteers whose ADH 2, ADH 3 and ALDH 2 genotypes were identical, were determined after intravenous administrations of 0.20 g/kg of ethanol by gas chromatography. The predicting 95% confidence bounds determined on regression analysis of these data suggested that after venous injection of ethanol, the blood ethanol concentration in a volunteer normal homozygous for CYP2E1 (C1/C1) is higher than that heterozygous (C1/C2). And beta 60 (the blood ethanol concentration-time curve) of the subject heterozygous for CYP2E1 (C1/C2) was higher than that normal homozygous (C1/C1). It is possible that the C2 allele corresponding to the higher CYP2E1 activity may affect the ethanol metabolism.

Aldehyde Dehydrogenase↗

PubMed1995

[Case of pseudocoarctation associated with aneurysm of the descending aorta].

A 55-year-old man was hospitalized for examination of a descending aortic aneurysm found on chest X-ray film. Aortogram and magnetic resonance imaging showed elongation and kinking of the arch and proximal descending aorta, which is associated with a descending aneurysm. A slit-like area of stenosis was found at the beginning of the aneurysm, but there was no pressure gradient across the stenotic lesion. The diagnosis of pseudocoarctation with aneurysm was done, and an operation was undertaken. The aneurysm and the kinking distal to the left subclavian artery were resected, and an artificial graft was inserted using partial cardiopulmonary bypass. This case is the tenth of pseudocoarctation associated with aneurysm reported in Japan.

Aortic Aneurysm, Thoracic↗

PubMed1995

Determination of the new fluoroquinolone balofloxacin and its metabolites in biological fluids by high performance liquid chromatography.

A sensitive high performance liquid chromatographic method for the determination in biological fluids of 1-cyclopropyl-6-fluoro-1,4- dihydro-8-methoxy-7-(3-methylaminopiperidin-1-yl)-4-oxoquinoline-3 -carboxylic acid dihydrate (CAS 127294-70-6, balofloxacin, Q-35), a new fluoroquinolone, as well as its metabolites, has been developed. Balofloxacin and its metabolite, N-desmethyl balofloxacin, were separated and determined by reversed-phase column with fluorescence detection. Balofloxacin glucuronide was determined as balofloxacin after alkali hydrolysis. This method exhibited good precision and accuracy. Furthermore, it is a simple method and requires only a small amount of samples, and therefore should be useful for pharmacokinetic studies in animals and humans.

Animals↗

PubMed1995

Pharmacokinetics of the new fluoroquinolone balofloxacin in mice, rats, and dogs.

The pharmacokinetics of 1-cyclopropyl-6-fluoro-1, 4-dihydro-8-methoxy-7-(3-methylaminopiperidin-1-yl)-4-oxoquinoline -3-carboxylic acid dihydrate (CAS 127294-70-6, balofloxacin, Q-35), a new fluoroquinolone, were studied in mice, rats and dogs by high performance liquid chromatography. The mean oral bioavailabilities of balofloxacin calculated from the area under the curve after oral and intravenous administration in mice, rats and dogs were 19.03, 87.50 and 87.73%, respectively, indicating that balofloxacin was almost completely absorbed in rats and dogs but not in mice after single oral administration. The mean elimination half-lives in plasma after intravenous administration in mice, rats and dogs were 0.92, 1.33 and 6.38 h, respectively. Mean cumulative urinary excretion percentages of unchanged balofloxacin within 24 h of oral administration of balofloxacin at the dose of 20 mg/kg in mice, rats and dogs were 4.91, 21.77 and 22.49% of the dose, respectively. A small portion of the metabolite was excreted into urine as balofloxacin glucuronide and N-desmethyl balofloxacin in these species. After oral administration of balofloxacin at the dose of 100 mg/kg to rats, absorption was prolonged compared with that after administration at the doses of 5 and 20 mg/kg. Plasma concentration-time profiles and pharmacokinetic parameters of balofloxacin in male rats were similar to those in female rats, indicating no sex-related differences. Once daily 21-day multiple administrations had not affect on these pharmacokinetic profiles of balofloxacin in rats.

Administration, Oral↗