Biomedical subjects

H Higashi

Publications and source records attributed to H Higashi.

At least 127 records · Page 7Linked to original sources

PubMed1994

Involvement of CD11b/CD18 in enhanced neutrophil adhesion by Fc gamma receptor stimulation.

Neutrophils showed a rapid and transient adhesion to immunoglobulin G (IgG)-coated plates compared with their adhesion to bovine serum albumin (BSA)-coated plates: the adhesion reached a peak after 15 min of incubation and then gradually returned to almost the basal state in 60 min. The addition of monomeric IgG or anti-Fc gamma RII monoclonal antibody (mAb) (IV.3) suppressed the increase in adhesion, whereas anti-Fc gamma RIII mAb (3G8) was hardly effective, indicating that the interaction of Fc gamma R, especially Fc gamma RII, with coated IgG is involved in the process. Adhesion was also blocked by cytochalasin B, suggesting that functional actin filament structures are crucial. Protein kinase inhibitors, erbstatin and genistein, inhibited the adhesion in a dose-dependent manner. The adhesion was inhibited by anti-CD11b (M1/70) and anti-CD18 (MHM23, TS1/18) mAbs. Moreover, neutrophils from a patient with complete leukocyte adhesion deficiency syndrome did not show increased adhesion to IgG-coated plates. The adhesion of neutrophils to fibrinogen- and BSA-coated plates was also increased when Fc gamma R was stimulated in the fluid phase with soluble aggregated IgG, which was also inhibited by anti-CD11b mAb. Stimulation of neutrophil Fc gamma R with soluble aggregated IgG enhanced the expression of CD11b in concert with the enhanced adhesion. These data collectively suggest that stimulation via Fc gamma R evokes a tyrosine kinase-dependent and actin filament-dependent intracellular signal that enhances the specific and nonspecific adhesive activity of neutrophils, presumably through the activation of CD11b/CD18.

Adult↗

PubMed1994

Serum hyaluronic acid for the assessment of graft viability in porcine liver transplantation.

For the assessment of graft viability, serum hyaluronic acid (HA) levels during porcine orthotopic liver transplantation were measured in two groups: group 1 (viable: n = 5) in which allografts were transplanted following a minimal cold (4 degrees C) preservation, and group 2 (nonviable: n = 4) in which allografts were transplanted after cold static storage (4 degrees C) for 24 h in University of Wisconsin solution. The changes in the HA levels reached a significant difference between the two groups at 30 min after reperfusion (P < 0.02). In group 1, all animals survived for over 4 days, while all animals in group 2 died within 24 h. The serum HA also demonstrated a significant correlation with prothrombin time, beta-glucuronidase, and aspartate aminotransferase at 120 min after reperfusion. These results suggest that the measurement of serum HA is a potentially effective index for evaluating hepatic allograft viability.

Animals↗

PubMed1994

Increased expression of Na+/H+ exchanger in the injured renal tissues of focal glomerulosclerosis in rats.

The renal mRNA expression of Na+/H+ exchanger (NHE) and the effects of NHE inhibitor, amiloride, on renal injury were investigated in adriamycin (ADR)-induced glomerulosclerosis model in rats, which progressively developed extensive glomerulosclerosis and interstitial fibrosis. NHE-1 mRNA from the cortex of the ADR rats progressively increased at weeks 4 and 8 and then peaked at week 16, which paralleled with the degree of glomerular sclerosis and interstitial fibrosis. The interstitial fibrosis in the ADR-rats was prevented by a daily administration of amiloride. A simultaneous analysis of the effects of a high salt diet on NHE-1 mRNA expression or renal injury was performed in the ADR rats at weeks 2 and 8. Renal or glomerular hypertrophy was observed in the control or ADR rats fed an 8% NaCl diet at week 2 and 8 compared to a 1% NaCl diet, while the NHE-1 mRNA expression was not up-regulated by an 8% NaCl diet at week 2. At week 8, the NHE-1 mRNA expression or glomerulosclerosis and interstitial fibrosis were enhanced in the ADR rats fed an 8% NaCl diet compared to a 1% NaCl diet. This histological aggravation by an 8% NaCl diet was prevented by a daily administration of amiloride but not by furosemide. In conclusion, the increased NHE-1 mRNA expression and the preventive effects of amiloride on the renal lesions suggest a potential importance of NHE in the progressive process of ADR-nephropathy. The high salt diet had a hypertrophic and destructive effect on kidney or glomeruli in the ADR rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗

PubMed1994

Acute effects of interstitial hyperthermia on normal monkey brain--magnetic resonance imaging appearance and effects on blood-brain barrier.

The magnitude and time course of histological and neuroradiological changes due to interstitial hyperthermia in normal cerebral white matter were investigated in eight adult Japanese monkeys. A cooling system enveloping a 2450-MHz microwave antenna was inserted stereotactically into the brain under general anesthesia. A point located 5 mm away from the surface of the cooling system was used as the reference point (RP). Hyperthermia was given to maintain the RP at 43 degrees C for 60 minutes. Two animals were sacrificed under general anesthesia following the intravenous administration of Evans blue, immediately and 1, 3, and 7 days after treatment. After removing the brain, histological changes were investigated. Magnetic resonance (MR) imaging was performed at 1, 3, and 7 days after treatment. Evans blue extravasation was most prominent in the region heated to 43 degrees C or above immediately after treatment. MR imaging showed obvious enhancement in the region heated to 43 degrees C or above 1 day after treatment, related to the disruption of the blood-brain barrier (BBB) by hyperthermia. Three days after treatment, ring-like enhancement with a central low-intensity area was seen in the region heated to about 43 degrees C, caused by BBB disruption and slight neovascularization. One week after treatment, an enhanced ring was observed in the region heated to less then 43 degrees C which surrounded a low-intensity area. The enhancement seen 1 week after treatment was caused by prominent neovascularization. T2-weighted imaging showed a high-intensity area, caused by edema, most prominent 3 days after treatment. Thus chemotherapeutic agents should be given just before the end of hyperthermia.

Animals↗

PubMed1994

Chloride-dependent potentials and their effects on firing pattern in guinea-pig cingulate cortical neurons.

Intracellular recordings were made from pyramidal neurons in the anterior cingulate cortex layer V of the guinea-pig slice preparation. An oscillation in membrane potential occurred when the membrane was depolarized to a subthreshold level (e.g. -60 mV), and the oscillation triggered repetitive firing. The frequency of the spontaneous firing varied with the membrane potential: frequencies were 2.9 +/- 1.4, 6 +/- 1, 13 +/- 3, and 17 +/- 3 Hz at the membrane potentials of -60, -58, -55, and -40 mV, respectively. Bicuculline (500 nM to 10 microM) increased the firing rate when the membrane potential was kept around threshold level by DC current injection. 2-Hydroxysaclofen and low Cl- (43 mM) also increased the firing rate, but 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonate (SITS, 250 microM) did not change the firing rate. Strychnine (1 to 3 microM) had no effect on the spontaneous firing. These results suggest that the firing frequency of cingulate pyramidal neurons is modulated by GABA tonically released by interneurons.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1994

[Synergistic effect of carboplatin and hyperthermia in rat and human glioma cell lines].

To assess the interaction of carboplatin and hyperthermia in vitro, the thermochemosensitivities of three glioma cell lines, C6 rat glioma cell line, human glioma cell lines T98G and KMG4, were examined by 3-(4,5-dimethylthiazol-2-yl) -2,5 diphenyltetrazolium bromide (MTT) assay. The cell survival of each cell line decreased according to increasing CBDCA concentration and temperature. With a certain CBDCA concentration, the cell survival at following temperature was significantly decreased from that at 37 degrees: 43 degrees C and 44 degrees C for C6 cells (2.5 micrograms/ml); 41 degrees C, 42 degrees C, 43 degrees C and 44 degrees C for C6 cells (128 micrograms/ml); 42 degrees C, 43 degrees C and 44 degrees C for KMG4 cells (8 micrograms/ml) (CBDCA concentration within parentheses). It is generally considered that the highest tolerable temperature of normal brain is 42 degrees C for 60 minutes, while under 43 degrees C, there is a possibility that a sufficient tumoricidal effect might not be obtained. This study revealed enhanced cytotoxicity of CBDCA with hyperthermia at the temperature lower than 42 degrees C and suggests the possibility to gain increased tumoricidal effect without injuring normal brain by hyperthermia at the normal-tissue-tolerant temperature with systemic administration of relatively lower dose of CBDCA.

Animals↗

PubMed1994

[Clinical pharmacokinetics of carboplatin and MCNU in malignant brain tumor and normal brain tissues].

We measured the concentrations of MCNU and CBDCA in the serum, brain tumor and normal brain tissue. Six patients with malignant glioma were treated with intravenous chemotherapy using 80mg/m2 MCNU and 300mg/m2 CBDCA during surgery. After drug administration, specimens of serum, tumor and normal brain tissue were collected every 30 min and then the drug concentration in each sample was measured. The highest MCNU levels in all samples were obtained immediately after administration which followed by gradual decrease. On the contrary, the mean CBDCA levels in the tumor and normal tissue remained almost at a constant level, although serum CBDCA level declined rapidly as MCNU. As expected, MCNU seemed to have advantages in the treatment of brain tumors as it distributed with higher concentration in the tumor tissue than in the serum and normal brain tissue. On the contrary, CBDCA in the tumor tissue did not exceed the concentration in the serum. Nevertheless, it remained longer in the tumor tissue with a constant level, suggesting that CBDCA can achieve an effective area under the concentration versus time curve (AUC) in the brain tumor tissue to kill tumor cells.

Aged↗

PubMed1994

Influence of hepatectomy on cell infiltration in the resected liver parenchyma compared with the biopsy specimen--a preliminary study.

We undertook a preliminary investigation to determine whether or not preoperative hepatitis activity can be evaluated by the finding of cell infiltration into the parenchyma of the resected specimen. In 28 patients who underwent hepatic resection, liver biopsies were obtained just after the laparotomy in order to make a histological comparison with the resected liver specimen. Histological changes were observed in 11 out of 28 patients. However, these were limited to minimal changes of neutrophil infiltration in the portal and subserosal area with no derangement of chronic cell infiltration. In addition, the preoperative liver function and operative findings did not differ between patients with and those without histological changes. The activity of hepatitis was therefore seen not to be histologically influenced by the surgical procedure. Thus, an accurate evaluation of chronic inflammatory cell infiltration activity in the resected liver specimen is a reliable indicator in chronic liver disease patients.

Adult↗

PubMed1994

Indications for major hepatectomy in cirrhotic liver.

In an investigation of the indications for major hepatic resection of the cirrhotic liver, the records of 152 consecutive patients who had undergone a right hepatic resection between April 1985 and January 1991 were reviewed. A comparison of right hepatic lobectomy and right partial hepatectomy of the liver with no cirrhotic changes, revealed that postoperative values of serum glutamic pyruvic transaminase were significantly higher after right partial hepatectomy than after right lobectomy, despite the fact that there were no significant differences with respect to preoperative laboratory data, and there was a greater blood loss and total weight of the resected liver in patients receiving a right lobectomy as compared with those undergoing partial hepatectomy. These results suggest that in order to enable a more favorable recovery from hepatic resection, it is essential to avoid both mechanical damage and ischemic injury to the residual liver during hepatic surgery. A total of 77 patients underwent a partial hepatectomy of a cirrhotic liver, and among these patients, 16 patients had values of the indocyanine green test of less than 20%, as well as a portal pressure of less than 200 mm saline. Compared with these 16 cirrhotic patients and those patients who underwent right lobectomy, there were no significant differences with regard to the pre-operative laboratory data and portal pressure. These results therefore suggest that major hepatic lobectomy could be performed on selected patients with cirrhotic livers.

Adult↗

PubMed1994

A cyclin-dependent kinase inhibitor, butyrolactone I, inhibits phosphorylation of RB protein and cell cycle progression.

Butyrolactone I is a selective inhibitor of the cyclin-dependent kinase (cdk) family. It inhibits both cdk2 and cdc2 kinase, but scarcely affects C-kinase, A-kinase, casein kinases, MAP kinase or EGF receptor-tyrosine kinase (Kitagawa et al., 1993, Oncogene, 8, 2425-2432). We studied the effects of butyrolactone I on the cell cycle as well as on phosphorylation of retinoblastoma protein (pRB). Butyrolactone I inhibited phosphorylation of pRB catalyzed by cyclin A-cdk2 produced by baculovirus in vitro. Furthermore, it inhibited phosphorylation of pRB and cell cycle progression from G1 to S phase in WI38 cell cultures. WI38 cells arrested at the G0 phase by serum starvation progressed in the cell cycle after serum stimulation. pRB was phosphorylated after 10 h serum stimulation. Incorporation of [3H]thymidine into the cells began to increase after 16 h serum stimulation. These processes were inhibited by butyrolactone I. Flow cytometric analysis showed that exposure to butyrolactone I inhibited progression of the cell cycle from G1 to S phase. These data suggested that initiation of DNA synthesis was inhibited by butyrolactone I and that the cell cycle was arrested in the G1 phase. Butyrolactone I also inhibited H1 histone phosphorylation in human WI38 cells and their G2/M progression. tsFT210 cells, a temperature-sensitive cdc2 mutant cell line, were synchronized at G2/M at a nonpermissive temperature, butyrolactone I inhibited the cell cycle progression of these cells at G2/M at the permissive temperature. Thus butyrolactone I, a cyclin-dependent kinase family inhibitor, which prevented the phosphorylations of the cell cycle-regulating proteins pRB and H1 histone, inhibited the cell cycle at G1/S and G2/M, respectively. These results suggest that the phosphorylations of pRB and H1 histone may play crucial roles in G1/S and G2/M progression, respectively, although it is possible that phosphorylations of other proteins by cdks are involved in G1/S and G2/M progression.

4-Butyrolactone↗

PubMed1994

[A case of pineal region germinoma treated by interstitial brachytherapy].

Although radiation therapy has been universally accepted as treatment for primary intracranial germinomas, the optimal technique for both diagnosis and treatment continues to be a matter of controversy. We report a case of germinoma in the pineal region treated by interstitial brachytherapy. A 23-year-old female was admitted with diplopia and consciousness disturbance. Magnetic resonance imagings (MRI) revealed an enhanced tumor of the pineal region and hydrocephalus. No serum and CSF tumor markers such as alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) or placental alkaline phosphatase (PLAP) were detectable. Stereotactic needle biopsy was performed using BRW MRI-guided stereotactic apparatus. After the histological diagnosis confirmed the presence of germinoma, three catheters for interstitial brachytherapy were implanted into the tumor through the biopsy tract, and iridium-192 seeds were inserted into the catheters and kept there for 5 days to give 35 Gy of irradiation at the tumor periphery. Subsequent MRI showed marked tumor regression and the clinical symptoms were gradually improved, and Gd-enhanced tumor on MRI completely disappeared 2 months after brachytherapy. Histological diagnosis is essential before initiation of treatment because a germinoma is commonly thought to be radiosensitive. However, pineal region tumor is dangerous to remove surgically because of high morbidity and mortality rates. Image-guided stereotactic technique provides a safe method to obtain an accurate diagnosis, and subsequent interstitial brachytherapy enables selective irradiation of the tumor, and does not give rise to complications caused by external irradiation such as mental disturbance, hypopituitarism, visual disturbance and brain necrosis. Interstitial brachytherapy following image-guided biopsy can be a useful tool for patients with germinoma.

Adult↗

PubMed1994

[Patterns of recurrence in malignant gliomas after brachytherapy].

More than 80% of malignant gliomas have been reported to recur locally after conventional chemoradiation therapy. This regional pattern of recurrence has encouraged the introduction of new treatments for local tumors. Since 1987 interstitial brachytherapy using Iridium-192 seeds has been carried out in our department for malignant brain tumors. The present study was designed to evaluate the patterns of recurrence following interstitial brachytherapy and to assess how this recurrence differs from that observed in patients treated by conventional means. Ten patients who satisfied the following criteria were selected among 41 patients treated with brachytherapy. The criteria were; 1) histologically diagnosed to be malignant glioma (astrocytoma grade III or glioblastoma), 2) followed up with MRI every month after the brachytherapy, 3) follow-up period was more than 6 months, and 4) the time of recurrence was confirmed. The patients were classified into 3 groups according to the patterns of tumor recurrence as follows; 1. Local recurrence group: The tumor recurred near the pretreatment tumor site. 2. Necrotomy group: Reoperation was performed because of neurological deterioration and radiographic evidence of increasing mass effect with surrounding edema. Neurological symptoms were unchanged or improving during the 6 months after the reoperation. 3. CSF seeding group: Primary tumor was well controlled, but seeding via cerebrospinal fluid was recognized on MRI. Local recurrence occurred in three patients, necrotomy was carried out in three patients, and CSF metastases were defined by both MRI and clinical symptoms in four patients. Median radiation does was 33 Gy in the local recurrence group, 57.6 Gy in the necrotomy group, and 43.2Gy in the CSF seeding group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Anti-tumor activity of ceramides and glycosphingolipids in a murine tumor system.

The anti-tumor activity of 7 sphingolipids, 2 ceramides and 5 glycosphingolipids against the syngeneic murine ascitic tumors MH134 and MM102 in C3H mice was examined. Five of these compounds showed anti-tumor activity against the tumors, ceramide type-IV (Cer-IV) having the highest activity without cytotoxic or cytostatic activity. These results indicate that the fatty acid in ceramide and sugar chains binding to it affect the anti-tumor activity in vivo. The anti-tumor activity of Cer-IV depended on the time of treatment. Mice treated with Cer-IV one day after tumor implantation showed the highest rate of survival. The cured mice were resistant to rechallenge with the same tumor (MH134-->MH134, MM102-->MM102) but not with a heterologous tumor (MH134-->X5563, MM102-->X5563), indicating that the effect of Cer-IV may be due to in vivo induction of specific immunity. Studies with various antibodies demonstrated that the anti-tumor effect of Cer-IV was inhibited by all the antibodies tested (L3T4, Lyt-2, and Thy-1,2 T cells, macrophages, and TNF alpha) in the induction phase (before Cer-IV administration) and by the antibodies of L3T4 and TNF alpha in the effector phase (after Cer-IV administration). Therefore, the anti-tumor effect of Cer-IV in this system depended on the host immune response rather than on its direct cytotoxic and/or cytostatic action.

Animals↗

PubMed1993

Profile of subjective complaints and activities of daily living among current patients with Minamata disease after 3 decades.

We surveyed 1144 current patients with Minamata disease (MD) aged 40 or over in the Minamata area and the same number of neighbor controls matched with age and sex by questionnaire interview with regard to subjective complaints and activities of daily living (ADL). From analysis of subjective complaints, it was found that MD patients had significantly higher rates of all complaints than controls (P < 0.05). Multivariate analysis showed that subjective complaints in controls were clearly separated into the following two categories: sensory disturbances and movement nerve disturbances, but all complaints in MD patients formed one cluster. Such variation seemed to be due to methylmercury exposure to the central nervous system. ADL analysis revealed that the difference in the ADL disability between MD patients and controls significantly increased with age (P < 0.05) and that ADL disability in MD patients was aggravated by aging.

Activities of Daily Living↗

PubMed1993

Open and closed suction drainage after hepatic resection.

A retrospective study was conducted to compare open conduit drains with closed suction drains, with regard to the occurrence of intraperitoneal septic complications after hepatectomy (IPSCH). The subjects comprised 50 consecutive Japanese patients who underwent hepatic resection followed by the insertion of a closed suction drain and the control group comprised 50 patients in whom a simple conduit drain had been placed following liver surgery. There were no significant differences between the two groups in sex, age, underlying liver disease, or the type of hepatectomy performed; nor was there a significant difference in the incidence of IPSCH, the simple conduit drain group versus the closed suction drain group being (10% versus 8%, respectively). However, bile leakage was highly related to IPSCH, the incidence being 60% and 100% in the simple conduit drain and closed suction drain groups, respectively. Thus, to prevent IPSCH, the treatment of bile leakage is a much more important factor than the type of drain used.

Aged↗

PubMed1993

Ionic mechanisms underlying the depolarizing and hyperpolarizing afterpotentials of single spike in guinea-pig cingulate cortical neurons.

Intracellular recordings and hybrid single-microelectrode voltage-clamp techniques were used to study the ionic mechanisms underlying the afterdepolarization and the subsequent slow afterhyperpolarization that followed a single action potential in layers V/VI neurons of the guinea-pig anterior cingulate cortex in in vitro slices. Both the afterdepolarization and afterhyperpolarization were markedly suppressed in size by addition of Co2+ or Cd2+, reduction in extracellular Ca2+, and intracellular EGTA injection. On the other hand, elevation of extracellular Ca2+ concentration augmented the amplitudes of the afterpotentials. The afterdepolarization amplitude was selectively depressed by the stilbene derivatives, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonate, disodium 3H2O, and 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid, disodium salt. Reduction in external Cl- and intracellular Cl- injection enhanced the afterdepolarization amplitude without affecting the afterhyperpolarization. The null potentials for the afterdepolarizations recorded with K acetate- and Cs acetate-electrodes were -68 and -63 mV, respectively. The slope of the null potential obtained with K acetate electrodes or Cs acetate electrodes was 49 and 53 mV, respectively, per log unit of the external Cl- concentration. Reduction in external K+ markedly depressed the afterdepolarization and augmented the afterhyperpolarization in size, whereas rise in external K+ markedly augmented the afterdepolarization and depressed the afterhyperpolarization. The null potential for the afterhyperpolarization recorded with K acetate electrodes was -94 mV. The slope of the null potential was 57 mV per log unit of the external K+ concentration. Reduction in extracellular Na+ concentration slightly depressed both the amplitudes of the afterdepolarization and afterhyperpolarization. A hybrid voltage-clamp analysis revealed a slow decaying inward current and a subsequent outward current that followed an action potential. Both the amplitudes of the inward current corresponding to afterdepolarization and the outward current corresponding to afterhyperpolarization were suppressed by addition of Co2+. Reduction in extracellular Cl- concentration augmented the inward current amplitude without significantly affecting the outward current. These results indicate that the afterdepolarization is mainly due to an increase in a Ca(2+)-activated Cl- conductance, while the afterhyperpolarization is mainly generated by an activation of Ca(2+)-mediated K+ conductance.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1993

Molecular cloning and heterogeneity of the human hepatitis C virus (HCV) genome.

The Japanese variant of the hepatitis C virus (HCV-N) genome, consisting of 9440 nucleotides in length, was cloned from a small amount (2 ml) of plasma from a single Japanese carrier by using RT-PCR and modified RT-PCR. The HCV-N genome has a long open reading frame that encodes a 3014 amino acid polyprotein with 340 and 57 bases of 5' and 3' non-coding sequences, respectively. HCV-N has a 4-amino-acid insertion in the NS5 region as compared to other HCV isolates, but this insertion is found to be very rare upon direct sequencing of that region. Comparative sequence analysis of all the complete and partial HCV sequences that were reported indicates that HCV can be subdivided into at least 4 groups. The HCV-N isolate has a high homology with HCV-J and HCV-BK (> 90%) and so belongs to group II, but shows less similarity to HCV-1 (> 78%, group I) and least to HC-J6 (> 67%, group III). Among these HCV isolates, the 5' non-coding region was the most conserved (> 93%) since it plays an important role in replication. The RT-PCR assay to detect HCV-RNA, using the primers deduced from this region, was very sensitive and specific. The putative core protein could become an important target for immunoassay because of a high degree of amino acid sequence similarity in that region. A high degree of diversity and a low similarity between each HCV isolate in the putative envelope protein play an important role in the chronicity of HCV infection and development of immunopreventive agents, such as immunoglobulin and vaccine for that infection.

Base Sequence↗

PubMed1993

Complete obstruction of right proximal pulmonary artery: a case report.

A fifty-five-year-old woman had worried about dyspnea for three years. A chest x-ray appeared normal except for hypovascularity of the upper lung field. On angiograms, a wedge-shaped obstruction was observed at the left proximal pulmonary artery, and well-developed collateral circulation from the right thoracic artery to the internal costal arteries was observed. On the exercise test, exertional dyspnea developed with tachycardia and a decreased saturation of arterial oxygen.

Arterial Occlusive Diseases↗