Search PubMed⌕ Search

Biomedical subjects

Y Higashi

Publications and source records attributed to Y Higashi.

At least 181 records · Page 10Linked to original sources
PubMed1993

Dynamics of genome change in the E2/NS1 region of hepatitis C virus in vivo.

To substantiate and extend the quasispecies model of hepatitis C virus (HCV), we made a pairwise comparison in the nucleotide and deduced amino acid sequences for multiple recombinant clones of the E2/NS1 region, which derived from each blood sample taken from five patients of subtype II or subtype III infection at different stages. Sequence heterogeneity among the clones was generally high. The heterogeneity, however, changed temporally and appeared to be significantly lowered after interferon therapy. The temporal fluctuation involved selection of particular amino acids at particular positions, which had represented only a minor fraction or had been absent in the previous clones. Evolution of defective viruses was featured by most of the cases, the proportion of which also fluctuated temporally and was extremely high at a certain stage in one of the patients. A comparison was also made among the clones from different stages of each patient and revealed highly divergent clones. An extreme case of subtype III infection showed sequence differences well beyond those among chronologically and geographically different isolates of subtype I or subtype II, which were defined by the same calculation of available sequence data. These features of HCV genome suggest that the virus could circulate as an extremely heterogeneous population including defective viruses and that this heterogeneity lends itself to selection pressures including interferon therapy and host immune response. Our results also indicate an absolute need of population based approach in HCV genetics.

Aged↗
PubMed1993

Cerebellar degeneration in the Niemann-Pick type C mouse.

Chronological morphological changes and topographical distribution of degenerating Purkinje cells were studied in the murine model of Niemann-Pick disease type C (NPC mouse). Loss of Purkinje cells can be detected in the anterior vermis as early as 60 days of age, coinciding with early neurological signs, and progressed to total absence in the entire hemisphere and vermis with exception of nodules. Ultrastructurally, concentric lamellar inclusions were detected in the perikarya of degenerating Purkinje cells as well as in the focally enlarged branching points of their dendrites. Calbindin immunocytochemistry demonstrated dendritic pathology characterized by irregular contour of dendritic trees and decreased number of dendritic spines. Ubiquitin immunoreactivity revealed granular reaction products in the perikarya, dendrites and axons of Purkinje cells. Our studies demonstrated unique pathological features of Purkinje cells that involve perikarya, dendrites and axons in the NPC mouse.

Animals↗
PubMed1993

A pilot study of ribavirin and interferon beta for the treatment of chronic hepatitis C.

BACKGROUND: Chronic hepatitis C is a common and often progressive liver disease for which interferon alfa therapy widely spreads, but the beneficial response is frequently transient. Ribavirin is a nucleoside analog with a broad spectrum of antiviral action, and we investigated the efficacy of it in patients with chronic active hepatitis C. METHODS: We conducted a pilot study of oral ribavirin in patients with chronic active hepatitis C. Twenty-seven patients with hepatitis C virus RNA were randomly assigned to receive either 0.8-1.0 g of ribavirin daily or 3 MU of interferon beta three times weekly or combination of the two for 24 weeks. RESULTS: Ribavirin was tolerated well, and all completed the treatment schedule. Ribavirin decreased aminotransferase levels in all instances, and the mean value at termination decreased to half of the baseline level (P < 0.01), but the enzyme level increased after cessation of therapy in most cases. Ribavirin suppressed amounts of hepatitis C virus RNA in 4 of 9 patients, and 1 became negative during follow-up. Interferon alone (P < 0.05) or with ribavirin (P < 0.01) significantly decreased the viral population, resulting in sustained loss of viremia with normal enzyme levels in 2 of 9 and 3 of 9 patients, respectively, in each therapy during follow-up. CONCLUSIONS: These results indicate that ribavirin has a beneficial effect in some patients with chronic hepatitis C, although the antiviral effect is less than interferon beta. Large-scale trials are needed to determine whether the combination of interferon and ribavirin is of more benefit than interferon alone.

Adult↗
PubMed1993

Aqueductal stenosis due to mesencephalic venous malformation: case report.

The authors report the case of a 43-year-old woman with a venous malformation of the mesencephalon occluding the sylvian aqueduct. Neuroradiological investigations suggested aqueductal stenosis, while the presence of a venous malformation was diagnosed by both magnetic resonance imaging and an angiogram, and was visualized using a neuroendoscope. This is the first reported instance of a venous malformation being observed in situ and the subependymal course taken.

Adult↗
PubMed1993

Effect of recombinant human transforming growth factor beta 1 on immune responses in patients with chronic hepatitis B.

Studies were undertaken to examine the effect of recombinant human transforming growth factor beta 1 (rTGF-beta 1) on cellular and humoral immune responses of peripheral blood mononuclear cells (PBMC) from patients with chronic hepatitis B. The addition of TGF-beta 1 caused a significant dose-dependent inhibition of hepatitis B (HB) core Ag-stimulated interferon-gamma and antibody to HB core Ag production and proliferation of PBMC from chronic hepatitis patients and HB-immune donors. TGF-beta 1 also induced a significant reduction in pokeweed mitogen-stimulated IgG and IgM production, as well as phytohemagglutinin p-stimulated proliferative response of PBMC. The degree of inhibition of TGF-beta 1 did not differ between antigen-specific and -nonspecific cellular and humoral immune responses, and between control individuals and patients. Pretreatment study with TGF-beta 1 showed that the activities of T cells, B cells and monocytes were similarly inhibited. Further, TGF-beta 1 inhibited activities of HLA class I antigen-matched cytotoxic T cells from patients with chronic hepatitis B for HBV DNA-transfected HepG2 cells in a 51Cr release assay. The results suggest that TGF-beta 1 may play a role in the regulation of antigen-dependent and -independent immune responses in patients with chronic hepatitis B.

Adult↗
PubMed1993

In-vitro permeability to salicylic acid of human, rodent, and shed snake skin.

In-vitro permeability to salicylic acid of human, rodent, and shed snake skin has been examined for the purpose of selecting model membranes for human skin corresponding to different anatomic sites, since a marked regional variation is suggested among the different sites. The greatest permeability to salicylic acid was observed in the scrotum, that of the sole was negligible. The cheek, neck, and inguinal skin seemed more permeable than the breast, back, thigh, lower leg, or foot skin. Shed snake and skin of hairless rat were found to show similar permeability to human breast and thigh skin. Wistar rat and nude mouse skin showed similar permeability to human cheek, neck, and inguinal skin.

Animals↗
PubMed1993

Animal pharmacokinetics of FK037, a novel parenteral broad-spectrum cephalosporin.

Single-dose pharmacokinetics of FK037 has been investigated in laboratory animals. After bolus intravenous dosing with 20 mg/kg, the elimination half-life of FK037 varied in the species; with values of 0.27, 0.30, 0.97, 1.29 and 1.76 hours in mice, rats, rabbits, dogs and monkeys, respectively. The volume of distribution ranged between 260 ml/kg in rats and 390 ml/kg in dogs. These parameters approximated those of ceftazidime and cefpirome used as reference drugs. The renal clearance of FK037 was almost equal to glomerular filtration rate (GFR) in rabbits. Probenecid did not affect the elimination half-life of FK037 and its clearance ratio to GFR. These findings suggest that FK037 is solely excreted by glomerular filtration. FK037 readily penetrated into the tissues and inflammatory exudate fluid in rats, and the tissue level was highest in the kidneys, and decreased in the following order; lungs > heart > liver > spleen. Penetration of FK037, cefpirome and ceftazidime into the cerebrospinal fluid were determined using induced staphylococcal meningitis in rabbits. The penetration percentage ranged from 14.2 to 16.0% for these drugs with no significant differences. The major route of excretion of FK037 was via the kidney, with more than 74% of the dose being excreted in the urine within 24 hours after dosing to each species. Biliary excretion was low, 0.79% in rats. Bioautograms showed only unchanged drug in the plasma, urine and bile. Serum protein binding was low (8.8 to 17.6%) in all the species studied.

Animals↗
PubMed1993

In vitro antibacterial activity of FK037, a novel parenteral broad-spectrum cephalosporin.

FK037 is a new parenteral cephalosporin, which offers some advantages over the commercially available parenteral cephalosporins. It demonstrated potent broad-spectrum activity against clinical isolates of Gram-positive bacteria including methicillin-resistant staphylococci, and Gram-negative bacteria including Pseudomonas aeruginosa. Against clinical isolates of aerobic Gram-positive bacteria, FK037, like cefpirome, demonstrated more potent activity than ceftazidime, cefoperazone and ceftizoxime. It is noteworthy that FK037, on the basis of the MIC90s, was the most active of all the cephalosporins tested against methicillin-resistant Staphylococcus aureus (MRSA). It was similar in activity to cefpirome against methicillin-sensitive S. aureus (MSSA). Against clinical isolates of aerobic Gram-negative bacteria, FK037, like cefpirome, was superior to cefoperazone, similar to ceftazidime and inferior to ceftizoxime in activity. Against P. aeruginosa, FK037 was superior to cefoperazone, similar or slightly superior to cefpirome and inferior to ceftazidime in activity. However, FK037 exhibited significant activity against Citrobacter and Enterobacter which were highly resistant to ceftazidime, cefoperazone and ceftizoxime. FK037 had an advantage in that its bactericidal activity against S. aureus, Escherichia coli and P. aeruginosa at sub-MICs (1/2 or 1/4 the MIC) was much stronger than those of cefpirome and ceftazidime. Moreover, it exhibited potent bactericidal activity against MSSA, MRSA and P. aeruginosa in a pharmacokinetic in vitro model simulating human plasma concentrations after intravenous dosage of 0.125, 1.0 and 1.0 g, respectively. FK037 inhibited essential penicillin-binding proteins (PBPs), 1, 2 and 3 of S. aureus with a 50% inhibitory concentration (I50) of 0.58 micrograms/ml or lower. Of essential PBPs 3, 1a and 1b of E. coli and P. aeruginosa, FK037 inhibited PBP 3 at the lowest I50 (0.03 and 0.04 micrograms/ml, respectively) and PBPs 1a and 1b with I50 values of 2.7 micrograms/ml or lower. FK037, like cefpirome, was highly stable to hydrolysis by various beta-lactamases except Ic cephalosporinase from Bacteroides fragilis, and had extremely low affinity for beta-lactamases. Therefore, FK037 was more potent than ceftazidime in activity against beta-lactamase-producing bacteria except P. aeruginosa and Serratia marcescens. The ability of FK037 to penetrate the outer membrane of E. coli was slightly higher than that of ceftazidime, but slightly lower than that of cefpirome.

Anti-Bacterial Agents↗
PubMed1993

Relative immunogenicity of hepatitis B virus-encoded antigens as targets for cytotoxic T-cell response.

To analyse the immunological mechanism of hepatocellular injury in hepatitis B virus (HBV) infection, the immunoreactivity of HBV-encoded antigens as a target for cytotoxic T lymphocyte (CTL) response was examined using recombinant vaccinia virus (RVV) expressing surface protein (S), precore/core protein (PC), and core protein (C) of HBV. C3H/He mice (H-2k) were inoculated with each RVV. Their spleen cells were then harvested and stimulated in vitro with the histocompatible transfectant, which stably expressed hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core antigen (HBcAg), and used as effectors. As the targets, L cells (H-2k) infected with individual RVV were used. Cytotoxic test was performed with various combinations and ratios of effectors and targets. The reactivity of PC-primed effectors against PC-expressing targets was greatest with 71.4% specific lysis on average at an effector/target ratio of 12.5:1 among all the combinations. C-primed effectors against C-expressing target also revealed rather high cytotoxicity (specific lysis, 40.6% at an E/T ratio of 12.5:1). Furthermore, PC-primed and C-primed effectors showed a cross-reactivity to the targets expressing other nucleocapsid antigen, respectively. S-primed effectors showed less lytic activity against S-expressing targets (specific lysis, 18.4% at an E/T ratio of 12.5:1). The CTL responses were blocked by anti-CD8 and anti-major histocompatibility complex (MHC) class I antibodies, but not by anti-CD4 or anti-MHC class II. These findings suggest that endogenously synthesized nucleocapsid antigen, especially PC, is a dominant target for the MHC class I-restricted CTL in H-2k mice and that this system may work as an efficient model to study immunopathogenesis of HBV infection.

Animals↗
PubMed1993

[Combination therapy of ESWL and PNL for the staghorn calculi].

We have been engaged in the treatment of urinary tract calculi using extracorporeal shockwave lithotripsy (ESWL) and endourology techniques for more than 8 years. In the treatment of thin staghorn calculi, ESWL monotherapy is the first choice. On the other hand, combination of percutaneous nephrolithotomy (PNL) and ESWL is important for the treatment of thick staghorn calculi in order to avoid the stone street and side effects of shock waves. When the stone is made of hard components such as calcium oxalate monohydrate and cystine, combination of both methods is also useful. In the case of complicated staghorn calculi with isolated branches, open surgery such as nephrolithotomy or partial nephrectomy might be the choice.

Combined Modality Therapy↗
PubMed1993

[Benign hemorrhagic renal cyst mimicking cystic renal cell carcinoma].

We experienced four cases of benign hemorrhagic renal cyst which were indistinguishable from cystic renal cell carcinoma on ultrasonography, computer tomographic scanning, magnetic resonance imaging and angiography. Nephrectomy was performed in one case and enucleation of the mass in the other three. Pathological diagnoses were hemorrhagic septate cyst in two cases, cyst with inflammation containing old blood clots in one, and organized hemorrhagic cyst with calcification in one. Conservative surgeries should be considered when the definite diagnosis for renal hemorrhagic cysts is not made.

Adult↗
PubMed1993

Idiopathic retroperitoneal fibrosis: a case of unilateral lesion.

Here we report a case of idiopathic retroperitoneal fibrosis, a unilateral case, which resulted in remission by ureterolysis with intraperitonealization. A 24-year-old female was hospitalized because of hydronephrosis. Many examinations were performed with the suspicion of malignant disease, but no apparent cause was detected. We suspected idiopathic retroperitoneal fibrosis and performed surgical exploration. The pathological diagnosis was retroperitoneal fibrosis. Ureterolysis with intraperitonealization of the ureter was performed. Six months later, marked improvement of the right hydronephrosis was observed without steroid therapy.

Adult↗
PubMed1993

[Acute respiratory failure resulting from diffuse microscopic pulmonary tumor emboli by bladder cancer: a case diagnosed at autopsy].

A 71-year-old man who had undergone a total cystectomy and a transureterocutaneostomy more than a year earlier was admitted to our hospital on February, 1992 because of the chief complaints of anorexia and systemic bone pain due to multiple bone metastases of bladder cancer. At two weeks after the admission, he had a sudden attack of dyspnea. His chest reontgenogram revealed no significant abnormalities. He had repeated attacks and died of respiratory failure two days after the first attack. An autopsy disclosed diffuse microscopic pulmonary tumor emboli in the pulmonary arteries and arterioles of bilateral lungs, but there was no parenchymal metastasis. The metastatic lesions in the sinusoids of the liver were also occupied by numerous tumor emboli, suggesting that the tumor emboli in the lungs had derived from those in the sinusoids. Microembolization of the whole lung area must be considered as a cause of clinically unexplained dyspnea.

Aged↗
PubMed1993

Pilot study of ribavirin and interferon-beta for chronic hepatitis B.

Ribavirin is a nucleoside analog that inhibits the replication of many DNA and RNA viruses. To evaluate the efficacy of oral ribavirin, we randomly assigned 24 HBeAg-positive patients with chronic active hepatitis to a 12-wk course of treatment with 0.8 to 1.0 gm/ribavirin day, 3 mU interferon-beta three times a week intravenously or a combination of those drugs. Ribavirin, alone and in combination with interferon-beta, decreased hepatitis B virus levels in most patients, and mean serum hepatitis B virus DNA and DNA polymerase levels at the end of treatment were approximately half of baseline levels (p < 0.05). Interferon alone exerted the most inhibitory effect on hepatitis B virus activity (p < 0.01). During ribavirin treatment, changes in serum aminotransferase values varied considerably and the mean values did not change significantly, although interferon alone and the combination of interferon and ribavirin were associated with significant reductions in serum aminotransferase activities. Ribavirin was well tolerated, but we transiently reduced the dosage in two cases because of mild hemolytic anemia, although all patients completed the treatment schedule. The combination of interferon and ribavirin did not appear to result in greater toxicity. During the follow-up period (6 to 9 mo), HBeAg and hepatitis B virus DNA disappeared in one patient treated with ribavirin, in two treated with interferon and in two given the combination. These results indicate that ribavirin suppresses hepatitis B virus replication, although its effect is less than that of interferon, and that it may be useful as adjunctive therapy for chronic hepatitis B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Clinical assessments on pre-treatment prognostic factors in 138 patients with advanced prostatic carcinoma (stage D2)].

We investigated the prognostic factors in 138 patients with stage D2 prostatic cancer by univariate and multivariate analyses. Analysis was restricted to 8 pre-treatment parameters, that is, age, general condition (PS), pain, number of metastases on bone scan, acid phosphatase value, Gleason's primary pattern, secondary pattern, and nucleoli grading. In addition, 4 therapeutic modalities except routine endocrine therapy, that is, castration, oral administration of estramustine phosphate, of 5-fluorouracil (5-FU) or its analogue, and combination chemotherapy, during the whole treatment period were included in the analysis. Univariate analysis (Kaplan-Meier method) showed only PS to be a significant prognostic factor. Multivariate analysis (Cox's proportional hazard model) revealed that PS, Gleason's primary pattern, oral administration of 5-FU or its analogue and combination chemotherapy were significant prognostic factors. However, patients treated by combination chemotherapy had poorer prognosis and chi 2 values of combination chemotherapy was the highest among the four parameters cited above. These results suggested that the 8 pre-treatment parameters examined in this study were not sufficient for predicting the prognosis of each patient.

Acid Phosphatase↗
PubMed1993

[Usefulness of contact thermography for the evaluation of chemotherapeutic effectiveness in breast cancer].

We examined temperature differences between a cancerous breast and its counterpart normal one by contact thermography before and after preoperative chemotherapy, and evaluated the relationship between the changes in the thermograms and response to chemotherapy in six patients with breast cancer. We used the following definitions: 1) delta Tmean: temperature differences between a mean temperature of a cancerous breast and that of the contralateral healthy breast; 2) delta Tmax: temperature differences between a cancer-related hyperthermic area in a breast and the mirror area of contralateral breast; 3) and the thermal patterns in thermogram were estimated by the criteria of Tada et al. In responders the thermograms after chemotherapy indicated an improvement in the hyperthermic vascular pattern (HVP) or hyperthermic area and a decrease of delta Tmean and delta Tmax. In contrast, little or no changes were observed in the thermograms of non-responders. Degrees of changes in thermograms reflected the effectiveness of chemotherapy. Our study showed that chemotherapeutic effectiveness may be better evaluated by combining contact thermography with the present method measuring tumor sizes than by only the present one.

Adult↗
PubMed1992

Microglial cell response to neuronal degeneration in the brain of brindled mouse.

Reactive changes of microglia in response to neuronal degeneration were investigated in the brains of brindled mottled mice with immunocytochemical technique. This mutant has a genetic defect in copper metabolism and spontaneous neuronal degeneration develops around postnatal day 10, in particular in the parasagittal regions of the cerebral cortex and thalamus. The antibodies to macrophage specific antigen, F4/80 and to type-three complement receptor, Mac-1 were used for the study. Reactive morphological changes of microglia, which are immuno-reactive to the antibodies to F4/80 and/or Mac-1, were demonstrated in areas corresponding to those of neuronal degeneration, coincident with the emergence of cells expressing major histocompatibility complex class II, Ia, antigen. Some of the Ia expressing cells had morphological features of ramified microglia, while others were rod shaped with few processes and were mostly located in the perivascular regions. The focal nature of such cellular changes suggests that signal(s) from the degenerating neurons may be responsible for microglial activation and cellular expression of the Ia antigen in the brain of the brindled mouse.

Animals↗