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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 667 records · Page 37Linked to original sources

Evaluation of effective portal venous flow in chronic liver diseases using echo-Doppler flowmetry combined with per jejunal portal scintigraphy.

Portal circulation changes due to the progression of chronic liver disease and portal venous flow are also affected by pharmacotherapy. Thus, noninvasive measurement of effective portal venous flow (EPVF) is highly desirable. We evaluated EPVF under steady-state conditions using echo-Doppler flowmetry combined with per jejunal portal scintigraphy in 32 patients with chronic liver disease. After introduodenal administration of 37 MBq (1 mCi) of 123I-iodoamphetamine, scintigraphy of the pulmonary and hepatic regions was performed and a portosystemic shunt index (SI) calculated. EPVF was calculated as follows: EPVF = PVFx (1-SI/100). EPVF in chronic hepatitis, compensated cirrhosis and decompensated cirrhosis was 12.0 +/- 1.8 ml/min/kg, 10.3 +/- 1.6 ml/min/kg and 8.0 +/- 2.5 ml/min/kg, respectively. There were significant differences in EPVF between all groups, although PVF was similar in each group. EPVF correlated with liver function tests and was a better indicator of liver function than PVF. Measurement of EPVF may provide useful information in the management of patients with chronic liver disease.

Adult↗

[Natural type interferon-alpha (Namalwa) therapy for multiple myeloma complicated by hemolytic anemia].

A 45-year-old woman with Bence-Jones type multiple myeloma was treated with natural type alpha-interferon (Namalwa interferon), 3 million IU every other day subcutaneously. After about 5 months, she developed hemolytic anemia. However, screening tests for autoantibodies, including direct and indirect antiglobulin (Coombs' tests), were negative. This report is the first case in which hemolytic anemia appeared to be caused by natural type alpha-interferon. It is likely that interferons will be used in treating increasing numbers of patients and that more patients will develop this complication.

Anemia, Hemolytic↗

[Nucleolar organizer regions in meningiomas with reference to histopathological findings and recurrence].

A silver staining technique was used in the study of nucleolar organizer regions (Ag-NORs) in paraffin sections of 40 meningiomas. The specimens were divided into three groups as follows: typical (n = 24), atypical (n = 8) and recurrent (n = 8) groups, and the mean number of Ag-NORs was evaluated in three groups. The mean Ag-NORs number (mean +/- S.D.) of typical, atypical and recurrent group was 1.48 +/- 0.14, 1.82 +/- 0.16 and 2.05 +/- 0.23 respectively. The mean Ag-NORs number of atypical and recurrent groups was significantly greater than that of typical group. These results suggest that the proliferative potential of meningiomas and the risk of recurrence could be evaluated by quantification of Ag-NORs.

Adult↗

[Metastasis of hepatocellular carcinoma to the urinary bladder].

We report a case of metastasis of a hepatocellular carcinoma to the bladder. Clinically the tumor was suspected to be a primary bladder tumor with subsequent metastasis to the liver. However, the pathological diagnosis yielded different results. The tumor cells resembled liver cells and sometimes bile production was even observed. No therapy was available and the patient died of cachexia 6 months later.

Aged↗

Direct evidence for clonal destruction of allo-reactive T cells in the mice treated with cyclophosphamide after allo-priming.

It has previously been reported that a single i.p. injection of 200 mg/kg cyclophosphamide (CP) 2 days after priming with 10(8) donor spleen cells (SC) leads to donor-specific skin allograft tolerance in H-2 compatible, multiminor antigen incompatible murine strain combinations. It is speculated that the i.v. injection of donor cells may result in synchronized proliferation of donor-reactive host T cells and subsequently administered CP may specifically destroy these proliferating T cells in the periphery. Although this unique action of CP is considered to be a principal mechanism in this method, direct evidence has not yet been obtained. In the present article, this in vivo destructive effect of CP is clearly demonstrated by assessing detailed kinetics of host-derived blastoid T cells and donor (Mls-1a)-reactive V beta 6+ T cells in the model system of C3H mice rendered tolerant to AKR. Frequencies of the blastoid cells and V beta 6+ cells, which increased as a result of AKR priming, decreased rapidly with the administration of CP. C3H mice, which received AKR SC alone, also exhibited partial deletion of V beta 6+ T cells, but both tempo and magnitude of decrease in the frequency of V beta 6+ cells were quite different from those of the C3H mice given AKR SC and CP, which showed more rapid and profound elimination of V beta 6+ T cells. In accordance with these kinetic studies, in vitro proliferative response to Mls-1a antigens was greatly impaired in mice treated with SC and CP, whereas a low but appreciable response was detected in mice given SC alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Current status of thermoradiotherapy in cancer therapy].

The current status of thermoradiotherapy for cancer is reviewed. The usefulness of this combined treatment for superficial tumors, in which heating and thermometry are relatively easy to apply, has been clearly demonstrated by many clinical results. With recent technological advancements, the application of thermoradiotherapy to deep-seated tumors is increasing, and encouraging results have been reported for various tumors including brain tumors, carcinomas of the breast, lung, esophagus, liver, rectum, urinary bladder, and soft tissue tumors. Thermoradiotherapy seems a very promising treatment modality for various refractory malignancies.

Brain Neoplasms↗

Antipyrine concentrations in liver and blood monitored by microdialysis of unrestrained conscious rats.

A newly developed microdialysis probe for measurement of drugs in unrestrained, conscious animals was used for quantitation of antipyrine in liver and blood of rats. Microdialysis probe were implanted in the liver and right jugular vein of rats; antipyrine was then administered at a dose of 50 mg/kg i.p. The concentration of antipyrine was determined in the fluid from the two probes and compared with measurement made on blood drawn from the left jugular vein. The elimination half lives in serum, blood dialysate and hepatic dialysate were 2.24 +/- 0.09, 2.06 +/- 0.31 and 2.10 +/- 0.32 hrs, respectively; there were not significantly different statistically. The concentration of Na+, K+ and Cl- in the hepatic dialysate was stable at least for up to 12 hrs in anesthetized rats. In unrestrained, conscious animals these electrolytes were stable in hepatic dialysate for at least 48 hrs. Therefore, the microprobe should be useful for analysis of drugs in extra cellular fluids of rats liver for up to 48 hrs. These studies suggest that this microdialysis technique by employing the newly developed probe will be useful in many studies on pharmacokinetics and drug metabolism in the organ.

Anesthesia↗

Observations on morphology and electrophysiological properties of the normal and axotomized facial motoneurons in the cat.

The correlation between the morphology of facial motoneurons stained intracellularly with horseradish peroxidase and their physiological parameters was examined in cats following facial nerve section and in cats with intact facial nerve. A certain statistical relationship exists between cell size and excitability in normal neurons. After axotomy, facial neurons showed a slow conduction velocity and a low rheobasic current, but had a normal cell size. Physiological changes include repetitive firing in response to intracellular current injection, reflecting an increase in the excitability in the axotomized neurons.

Animals↗

Expression of mouse cathepsin L cDNA in Saccharomyces cerevisiae: evidence that cathepsin L is sorted for targeting to yeast vacuole.

To investigate the intracellular transport mechanism of lysosomal cathepsin L in yeast cells, we attempted to produce mouse cathepsin L in Saccharomyces cerevisiae by placing the coding region under the control of the promoter of the yeast glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene. Immunoblotting analysis by the use of an antibody specific for rat cathepsin L revealed that the yeast cells carrying the cathepsin L coding sequence produced 39- and 30-kDa products, which correspond to the rat procathepsin L and the single-chain form of mature cathepsin L, respectively. The precursor polypeptide showed sensitivity toward endoglycosidase H treatment. Cell fractionation experiments demonstrated that the processed form of 30-kDa cathepsin L was found to be colocalized to the yeast vacuole with the marker enzyme carboxypeptidase Y in a Ficoll step gradient. In the prepared vacuolar fraction, a considerable amount of cathepsin L was revealed to be cofractionated with the vacuolar membranes. Furthermore, the phase separation experiments with Triton X-114 provide the first evidence showing that the mature form of cathepsin L polypeptide is strongly associated with the vacuolar membranes. Therefore, the present results suggest that the mouse cathepsin L precursor polypeptide is initially synthesized as the proenzyme in the yeast cells and then correctly delivered to the vacuole. During the intracellular sorting pathway, the procathepsin L would undergo the post-translational proteolytic processing step to generate the mature enzyme. Based on these lines of evidence, we propose that cathepsin L is recognized by mechanisms similar to those for the intracellular sorting and processing of vacuolar proteins in the yeast cells.

Animals↗

Interference with cyclophosphamide-induced skin allograft tolerance by cyclosporin A.

In a murine strain combination identical in H-2 Ag but disparate in minor histocompatibility (H) Ag consisting of C3H/He (C3H; H-2k, Mls-1b) mice as recipients and AKR/J (AKR; H-2k, Mls-1a) mice as donors, a permanent skin allograft tolerance can be achieved by the cyclophosphamide (CP)-induced tolerance system that consists of i.v. injection of donor spleen cells (day -2) and i.p. injection of CP 2 days later (day 0). Such permanent take of allografts in CP-induced tolerant mice was interfered with by intramuscular injection of cyclosporin A (CsA) from day -5 to day -1 and their grafts were rejected by 21 days after grafting. Mls-1a-reactive CD4+V beta 6+ T cells in the periphery, as the indicator to follow the kinetics of donor-reactive T cells, increased on day 0 and day 3 in the C3H mice treated with AKR spleen cells alone, whereas they disappeared rapidly from day 0 to day 3 in CP-induced tolerant mice. When CsA capable of interfering with IL-2 production and T cell proliferation was administered before CP treatment in CP-induced tolerance system, the number of CD4+V beta 6+ T cells in periphery did not increase on day 0 and 3, but increased on day 7 in contrast to the decreased number of those in CP-induced tolerant mice. On day 7, MLR against donor cells was decreased in CP-induced tolerant mice, but maintained in CsA-interfered tolerant mice. These result may indicate that the destruction of donor-Ag-stimulated, proliferating T cells by CP is interfered with by CsA, probably because CsA inhibits the proliferation of donor-reactive T cells at the time of CP treatment. Furthermore, these results also implicate that the protocol for immunosuppression with CsA and antimetabolites has to be designed carefully in clinical transplantation.

Animals↗

Extraordinarily stable mini-hairpins: electrophoretical and thermal properties of the various sequence variants of d(GCGAAAGC) and their effect on DNA sequencing.

A small DNA fragment having a characteristic sequence d(GCGAAAGC) has been shown to form an extraordinarily stable mini-hairpin structure and to have an unusually rapid mobility in polyacrylamide gel electrophoresis, even when containing 7M urea. Here, we have studied the stability of the various sequence variants of d(GCGAAAGC) and the corresponding RNA fragments. Many such sequence variants form stable mini-hairpins in a similar manner to the d(GCGAAAGC) sequence. The RNA fragment, r(GCGAAAGC) also forms a mini-hairpin structure with less stability. The DNA mini-hairpins with GAAA or GAA loop are much more stable than DNA and RNA mini-hairpins with other loop sequence so far as has been examined. The stability difference between DNA and RNA mini-hairpins may be deduced to the stem structures formed by DNA (B form) and RNA (A form). The stable hairpins consisting of the GCGAAAGC sequence cause strong band compression on the sequencing gel. This phenomenon should be carefully considered in DNA sequencing.

Base Sequence↗

Solution structure of a DNA-binding unit of Myb: a helix-turn-helix-related motif with conserved tryptophans forming a hydrophobic core.

The DNA-binding domain of the c-myb protooncogene product consists of three imperfect tandem repeats of 51 or 52 amino acids, each of which contains three conserved tryptophans, spaced 18 or 19 amino acids apart. The structure of the third repeat, which is essential for sequence-specific DNA binding, has been determined by NMR with distance geometry calculation. It includes three well-defined helices (residues 149-162, 166-172, and 178-187) maintained by a hydrophobic core that includes the three conserved tryptophans, together with two histidines. Helices 2 and 3 form a structure related to but distinct from a canonical helix-turn-helix motif. In particular, the turn between these helices is one amino acid longer than the corresponding turn in bacterial repressors and homeodomains and contains a proline residue. In addition, the architecture of the three helices is different from those of homeodomains and DNA-binding domains of bacterial repressors. Based on the present structure, the binding mode of Myb repeat 3 with a specific DNA is also discussed.

Amino Acid Sequence↗

Synaptic inhibition of accessory motoneurons evoked by stimulation of the trigeminal nerve in the cat.

Stimulation of the trigeminal nerve produced polysynaptic inhibitory postsynaptic potentials (IPSPs) in accessory motoneurons of the cat. This contrasts with the observation that dorsal cervical motoneurons responded with EPSPs to trigeminal stimulus. Stimulation of the rostral part of spinal trigeminal nucleus elicited di- or polysynaptic IPSPs in accessory motoneurons. Transection of the anterior funiculus at the upper cervical cord selectively abolished the IPSPs. The IPSPs were antagonized by systematically administrated strychnine but not bicuculline.

Accessory Nerve↗

Afferent projections in the spinal accessory nerve to the facial motoneurons of the cat.

Stimulation of the accessory nerve evoked polysynaptic excitatory postsynaptic potentials (EPSPs) in the facial nucleus (FN) neurons of anesthetized cats. From the experiments with severance of C1-C3 dorsal roots, it is suggested that accessory afferents enter the brainstem through the accessory nerve. It was also found that stimulation of the solitary tract nucleus produced exclusively monosynaptic EPSPs in the FN neurons and the afferent volleys are most likely to be relayed at the solitary tract nucleus.

Accessory Nerve↗

Accelerated declining tendency of human T-cell leukemia virus type I carrier rates among younger blood donors in Kumamoto, Japan.

The annual age- and sex-specific human T-cell leukemia virus type I carrier rate of blood donors in Kumamoto, Kyushu, Japan from 1986 to 1990 revealed that the carrier rates of all the age groups below 50 years declined linearly in both sexes (P less than 0.005). Furthermore, the annual declining rates relative to the carrier rates of 16-19-year-old and 20-29-year-old males were higher than those of all of the older males (P less than 0.02), and all female age groups below 50 years had higher relative declining rates than 50-64-year-old females (P less than 0.05). Although several factors, such as a notification program at obstetric clinics, methodological and technical improvement of the assays, wider knowledge of human T-cell leukemia virus type I infection in the latter years, and immigration of individuals from a nonendemic area, might cause an absolute decline of the carrier rate of the blood donors, these factors could not explain the acceleration of the relative declining rate among younger donors. Therefore, this acceleration represents the tendency of the general population.

Adolescent↗

Genetic control of nonresponsiveness to hepatitis B virus vaccine by an extended HLA haplotype.

We previously reported evidence for a statistical association between the serologically determined HLA-Bw54, DR4 and DRw53 alleles and the non-immune responsiveness to hepatitis B virus surface antigen (HBsAg) in the Japanese population. To identify the locus and allele within the HLA region associated with the nonresponsiveness to HBsAg, serological HLA typing, DNA typing of HLA-DQ and DP alleles using amplified HLA genes and sequence-specific oligonucleotide probes, and restriction fragment length polymorphism (RFLP) analysis of the fourth component of complement (C4) genes were performed in healthy unrelated Japanese vaccinees who were immunized subcutaneously three times with plasma-derived HBsAg vaccine. In nonresponders to HBsAg, the frequencies of HLA-Bw54 cross-reactive epitope group (CREG); (Bw54, Bw55, Bw56 and other Bw22), C4 RFLP (6.5 kb + 12.0 kb), DR4, DRw53 and DQw4 (DQA1*0301-DQB1*0401) were increased and the frequencies of HLA-DR1, DRw6 and DQw1 were decreased as compared with those in healthy unrelated controls. Further analysis revealed that the coexistence of HLA-Bw54CREG and DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) was associated with the nonresponder group, whereas, donors positive for exclusively either Bw54 CREG or DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) were not associated with the nonresponder group. Because there is a strong linkage disequilibrium between HLA-Bw54CREG, C4 RFLP (6.5 kb + 12.0 kb) and HLA-DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) in the Japanese population, the extended HLA-Bw54CREG-C4 RFLP (6.5 kb + 12.0 kb)-DR4-DR-w53-DQw4 (DQA1*0301-DQB1*0401) haplotype may well control nonimmune responsiveness to HBsAg. This extended HLA haplotype controls nonresponsiveness as a dominant genetic trait because all ten heterozygotes and two of three probable homozygotes of this extended HLA haplotype were nonresponders.

Adult↗

Tumor necrosis factor and endotoxin in the pathogenesis of liver and pulmonary injuries after orthotopic liver transplantation in the rat.

This study examines whether tumor necrosis factor and endotoxin are involved in the pathogenesis of primary nonfunction of graft and pulmonary complication after orthotopic liver transplantation. Livers from Lewis rats were stored for either 1 or 4 hr in ice-cold Euro-Collins solution (1-hr storage and 4-hr storage group, respectively). Subsequently, donor livers were implanted orthotopically. In some experiments, anti-tumor necrosis factor antibody was administered intravenously before and immediately after the surgery into animals that received livers stored for 4 hr. Blood samples for the measurement of tumor necrosis factor and endotoxin were collected by way of an indwelling catheter placed in the suprahepatic vena cava. Serum tumor necrosis factor was elevated at all time points studied postoperatively in rats of the 4-hr storage group; however, tumor necrosis factor was not detected in the serum in the 1-hr storage group. Endotoxin was also elevated significantly in the serum of the former group compared with levels in the serum of the latter group. The peak value of endotoxin occurred 1 hr earlier than that of tumor necrosis factor, suggesting that the rise in endotoxin stimulated release of tumor necrosis factor. The histological study of livers stored for 4 hr showed substantial hepatocellular degeneration 24 hr after surgery, whereas hepatocellular damage was minimal in the 1-hr storage group. Serum ALT levels 24 hr after the operation in the 1-hr and 4-hr storage groups were 169 +/- 46 IU/L and 374 +/- 41 IU/L (mean +/- S.E.M., p less than 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗