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Biomedical subjects

K Yoshioka

Publications and source records attributed to K Yoshioka.

At least 253 records · Page 14Linked to original sources
PubMed1995

Immunohistochemical study of calpain and its endogenous inhibitor in the skeletal muscle of muscular dystrophy.

A calcium-dependent proteinase (calpain) has been suggested to play an important role in muscle degradation in Duchenne muscular dystrophy (DMD). In immunohistochemical studies, calpain and its endogenous inhibitor (calpastatin) were located exclusively in the cytoplasm in normal human muscles. The intensity of the staining was stronger in type 1 than in type 2 fibers. Quantitative immunohistochemical study showed an increase of calpain in biopsied muscles from the patients with DMD and Becker muscular dystrophy. Abnormal increases in calpain and calpastatin were demonstrated mainly in atrophic fibers, whereas necrotic fibers showed moderate or weak immunoreactions for the enzymes. Opaque fibers and hypertrophic fibers were negative. Not all dystrophin-deficient muscle fibers necessarily showed a strong reaction for calpain. We suggest that calpain may play an important role in muscle fiber degradation, especially in the early stage of muscle degradation in muscular dystrophy.

Adolescent↗
PubMed1995

The position of the patient does not adversely influence the results of the most clinically important measurements of anorectal function.

Anorectal physiological measurements were carried out in three groups of patients: Controls (n = 11), slow transit constipation (n = 21) and neuropathic faecal incontinence (n = 14) to examine whether the position of the patient influenced the result of tests of anorectal function. Measurements were made in both the conventional left lateral and the seated position. No significant differences were observed in the pressures within the anal canal at 2 cm from the anal verge, the usual site of maximum resting and maximum squeeze pressures, although, at 4 cm pressures were significantly different in the two positions. With all other tests including rectal compliance, anorectal inhibitory reflex and rectal sensation there was no significant difference due to position in any of the three clinical groups. We conclude that the left lateral position is generally satisfactory for measurement of the most clinically important aspects of anorectal function.

Adult↗
PubMed1995

A case of non-insulin-dependent diabetes mellitus with vertebral osteomyelitits: usefulness of imaging diagnosis.

A 63-year-old woman with NIDDM poorly controlled by insulin therapy was admitted to our hospital because of fever and severe lumbago. Laboratory data revealed diabetic ketosis and a hypercoagulable state with infection. Bone and gallium scintigrams revealed an abnormal accumulation of the isotopes at L4-L5, where magnetic resonance imaging showed inflammatory changes. The patient was then diagnosed as having pyogenic vertebral osteomyelitis. Antibiotic chemotherapy and the administration of gebexate mesilate improved the inflammation and hypercoagulable state. When diabetic patients suffer from severe lumbago with sustained fever, and show segmental knock pain along the spine, pyogenic vertebral osteomyelitis should be considered. Bone and gallium scintigrams, and MRI are of clinical value for the early diagnosis of the disease.

Blood Coagulation Disorders↗
PubMed1995

Serum HCV RNA titer at the end of interferon therapy predicts the long-term outcome of treatment.

BACKGROUND/AIMS: Serum HCV RNA was quantitated by the competitive polymerase chain reaction before, at the end of, and after interferon therapy. We assessed whether serum HCV RNA titer at the end of interferon therapy predicts the long-term outcome of treatment. METHODS/RESULTS: Of 71 patients treated with various doses of interferons, 21 became negative for HCV RNA persistently during follow up of 2 years, and they were considered as complete responders. The serial determinations of HCV RNA titer for each individual showed that in patients with HCV RNA negative at the end of therapy, the complete response rate was quite high (78.6%), while in patients with HCV RNA titer > or = 10(4) copies/ml at the end of therapy, none became complete responders in long-term follow up. The percentage decreasing to < or = 10(2) copies/ml of HCV RNA at termination of interferon tended to be higher in patients with genotype 2a (14/21, 66.7%) than in those with genotype 1b (18/42, 42.9%). The complete response rate of patients whose viral load was < or = 10(2) copies/ml at termination of interferon was significantly higher in genotype 2a (11/14, 78.6%) than in genotype 1b (5/18, 27.8%) (p < 0.01). Pretreatment HCV RNA titer appeared to correlate to the titer at the end of therapy (r = 0.596, p < 0.001); even when HCV RNA decreased to < or = 10(2) copies/ml, the higher pretreatment titer indicated a lower likelihood of complete response (p < 0.05). CONCLUSIONS: These results indicate that HCV genotype and pretreatment viral titer are important factors in the response to interferon therapy. In addition, our study suggests that it is possible to stop interferon therapy at an appropriate time by monitoring HCV RNA titer.

Adult↗
PubMed1995

Interferon gamma production by peripheral blood lymphocytes to hepatitis C virus core protein in chronic hepatitis C infection.

Evidence suggests that cellular immunity to hepatitis C virus (HCV) core protein may be important in the pathogenesis of viral infection. Therefore, interferon gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) derived from patients with chronic HCV infection (genotype 1b) was examined. The cellular immune response was evaluated with a recombinant HCV core fusion protein derived from a patient with genotype 1b. To identify the immunodominant epitopes, IFN-gamma production in responders was also assessed with a panel of nine synthetic peptides that covered the entire core region. It was found that mononuclear cells from 24 (52%) of 46 patients with chronic liver disease responded to the core protein; asymptomatic HCV carriers demonstrated a lower response rate (14%, P < .05). More important, individuals who had received IFN-alpha treatment and went into clinical and virological remission had a higher response rate (75%, P < .05) compared with those with ongoing hepatitis whose treatment failed (31%). Of 25 patients whose mononuclear cells responded to HCV core protein, 18 had a significant response to one or more peptides; 12 patients reacted to a peptide mixture containing hydrophilic sequences. The core peptide amino acid sequence 141 to 160 was recognized in 9 patients. Interestingly, 7 of 8 patients bearing HLA DR 4 and w53 haplotypes recognized the peptide sequence 141 to 160. Thus, IFN-gamma production of the mononuclear cell response appeared to be HLA DR restricted, and the responding cells were identified as CD4+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Characteristics of substance P-evoked release of amino acids from neonatal rat spinal cord.

The characteristics of release of amino acids evoked by substance P from the neonatal rat spinal cord were examined. A hemisected spinal cord was continuously perfused and the release of amino acids into the perfusate was measured using high-performance liquid chromatography with a precolumn derivatization technique. Substance P (10 microM) evoked a significant increase in the release of aspartate, glutamate, GABA, glycine and taurine. The substance P-evoked release of these five amino acids was not reduced by Ca(2+)-free medium, but was blocked by [D-Pro4,D-Trp] substance P4-11 (10 microM). Perfusion of the spinal cord with low-Na+ medium (22 mM) induced a marked increase in the high-K+ (90mM)-evoked release of GABA, glutamate and glycine. In contrast, the substance P-evoked release of the five amino acids was significantly decreased by the low-Na+ medium. Similarly, perfusion of the spinal cord with low-Cl- medium (8 mM) increased the high-K(+)-evoked release of GABA and glycine, but decreased the substance P-evoked release of GABA, glycine and taurine. The substance P-evoked release of the five amino acids was dose-dependently blocked by d-tubocurarine (3-10 microM), whereas it was not blocked by tetrodotoxin (0.2 microM) or amiloride (30 microM). Compound 48/80 (10 micrograms/ml), a histamine-releasing agent on mast cells, evoked release of the amino acids from the spinal cord with characteristics similar to those of substance P-evoked amino acid release.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1995

Effects of fatty acids and fatty acyl CoA esters on Cu(2+)-induced conversion of xanthine dehydrogenase to oxidase in rabbit liver.

Effects of various fatty acids and fatty acyl CoA esters on Cu(2+)-induced conversion of xanthine dehydrogenase to oxidase in rabbit liver were examined. Cu2+ (2-10 microM) brought about the conversion of xanthine dehydrogenase to oxidase in a dose-dependent manner. Oleic, arachidonic, eicosapentaenoic, and docosahexaenoic acids (50-200 microM) prevented the conversion of xanthine dehydrogenase to oxidase catalyzed by 6 microM-Cu2+. The effect of these four fatty acids was concentration-dependent, whereas palmitic, stearic, and linoleic acids had no effect on the conversion of xanthine dehydrogenase to oxidase at the same concentration range. On the other hand, palmitoyl, linoleoyl, and arachidonoyl CoAs elicited the inhibition of 6 microM-Cu(2+)-induced conversion of xanthine dehydrogenase to oxidase at concentrations of 50, 100, and 200 microM. These results suggest that oleic, arachidonic, eicosapentaenoic and docosahexaenoic acids, and fatty acyl CoAs have the potential to inhibit the conversion of xanthine dehydrogenase to oxidase in rabbit liver.

Acyl Coenzyme A↗
PubMed1995

Expression of Fas antigen and Bcl-2 in human glomerulonephritis.

To understand the regulatory mechanism of apoptosis in human glomerulonephritis, we examined the expression of Fas antigen (CD95) and Bcl-2 in five normal human kidney specimens and 80 tissues from patients with several types of glomerular diseases. These proteins were detected in glomeruli by immunofluorescence. The number of intraglomerular cells positive for Fas antigen was high in Henoch-Schönlein purpura nephritis and lupus nephritis, and that of Bcl-2-positive intraglomerular cells was high in lupus nephritis, focal glomerular sclerosis, and IgA nephritis. Dual-labeling and staining on serial sections indicated that mesangial cells and occasionally infiltrating leukocytes expressed Fas antigen and Bcl-2. In situ hybridization detected Bcl-2 mRNA in glomerular cells. Electron microscopy revealed apoptotic cells and apoptotic bodies in proliferated mesangial areas and within the glomerular capillaries. Fragmented DNA was detected in glomeruli by in situ nick end labeling, the data of which paralleled the number of Fas antigen-positive intraglomerular cells. In mesangial proliferative types of glomerulonephritis, the population of Bcl-2-positive intraglomerular cells, but not that of Fas antigen-positive cells, was significantly correlated with the number of proliferating cell nuclear antigen-positive glomerular cells, the grade of mesangial cell increase, and the magnitude of proteinuria. This study showed that Fas antigen and Bcl-2 are up-regulated in the glomeruli of several types of human renal diseases. Bcl-2 overexpression might play a role in the prolonged proliferation of mesangial cells and glomerular hypercellularity in glomerulonephritis.

Apoptosis↗
PubMed1995

Probucol prevents the progression of fatty liver in MSG obese mice.

We investigated the effect of Probucol in preventing fatty liver in monosodium-L-glutamate (MSG) treated obese mice and control mice fed a high fat diet. MSG mice became significantly obese 9 weeks after birth with higher levels of serum blood glucose, total cholesterol, HDL-cholesterol, GPT, and cholinesterase, and had greater triglyceride contents in their livers relative to control mice. Morphologically, MSG obese mice also had a marked fatty liver. Administration of Probucol mixed with the high fat diet for 2 weeks significantly decreased the serum levels of total cholesterol and HDL-cholesterol, and liver triglyceride contents in both MSG and control mice. Morphologically, the livers were less fatty after Probucol treatment. These results suggest that Probucol prevents the development of fatty liver, and in addition reduces hypercholesterolemia.

Animals↗
PubMed1995

Myxoma of the mitral valve detected by echocardiography and magnetic resonance imaging.

Myxomas of the mitral valve diagnosed during life are exceedingly rare. We employed transthoracic and transoesophageal echocardiography and magnetic resonance imaging enhanced by gadolinium-diethylene-triamine-pentaacetic acid in a patient with palpitations. After these examinations clearly demonstrated a myxoma on the atrial side of the posterior mitral valve leaflet, urgent surgery was performed. When a small tumour of the mitral valve exists, these examinations are useful not only for detecting and characterizing the tumour, but also for deciding the optimal surgical management.

Adult↗
PubMed1995

Alterations of sympathovagal balance in patients with hypertrophic and dilated cardiomyopathies assessed by spectral analysis of RR interval variability.

Spectral analysis of RR interval variability was performed in 35 ambulatory patients with early hypertrophic cardiomyopathy (HCMa, NYHA class I), 21 hospitalized patients with advanced hypertrophic cardiomyopathy (HCMh, NYHA class II or III), and 18 hospitalized patients with dilated cardiomyopathy (DCMh, NYHA class I, II or III). Twenty-nine ambulatory subjects (COTa) and 20 hospitalized volunteers (COTh) served as normal controls. The RR interval standard deviation (SD), the high-frequency power (HF: 0.15-0.40 Hz) corrected by the mean RR interval (CCVHF) and the normalized unit of the HF power (NUHF) served as markers of vagal modulation. Low-frequency power (LF: 0.04-0.15 Hz) corrected by the mean RR interval (CCVLF) and the normalized unit of LF power (NULF) were markers of sympathetic modulation. The LF/HF ratio was an index of sympathovagal balance. There was no significant difference in the SD, CCVHF, NUHF, CCVLF, NULF or the LF/HF ratio between the HCMa and COTa groups. At night, the SD was lower in the HCMh group relative to the COTh group (P < 0.01). The HCMh group demonstrated lower CCVHF and NUHF values (P < 0.01), higher NULF values (P < 0.01) and higher LF/HF ratios (P < 0.05) at night relative to the COTh group. Two patients who later died suddenly in the HCMh group had markedly reduced CCVHF values (0.2-0.8%) relative to the survivors in the group (mean +/- SD in the morning, afternoon and night, 1.07 +/- 0.43%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Subtypes of tachykinin receptors on tonic and phasic neurones in coeliac ganglion of the guinea-pig.

1. Intracellular recording techniques were used to investigate the characteristics of tachykinin receptors and their subtypes in tonic and phasic neurones, which constituted two major neuronal populations in the coeliac ganglion of the guinea-pig. 2. In 95% of phasic neurones a long-lasting after-hyperpolarization (LAH), 5-8 s in duration and 10-20 mV in amplitude, was observed following action potentials evoked by passing a train of depolarizing current pulses into the neurones. In contrast, LAH was observed in only 4% of tonic neurones. 3. In most tonic neurones, substance P (SP), neurokinin A (NKA) and senktide induced depolarizations, whereas in phasic neurones they usually inhibited LAH but rarely induced depolarization. 4. Tonic and phasic neurones were further classified into three groups based on their responses (depolarization for tonic neurones and LAH inhibition for phasic neurones) to these tachykinin receptor agonists: (1) neurones responsive to SP, NKA and senktide (71-78%); (2) those responsive to senktide but not to SP and NKA (12-23%) and (3) those not responsive to any of the three agonists (7-11%). 5. GR71251 (5 microM), an NK1-selective tachykinin receptor antagonist, depressed the depolarization in tonic neurones and the LAH inhibition in phasic neurones induced by SP and NKA, but not those induced by senktide. 6. Selective NK2 receptor agonists, [Nle10]NKA4-10, [beta-Ala8]NKA4-10 and GR64349, were without effect in both tonic and phasic neurones. Furthermore, an NK2 receptor antagonist, L659,877, did not inhibit the depolarization induced by NKA, SP or senktide in tonic neurones. 7. It is suggested that NK1 and NK3 receptors are present on a large proportion of coeliac ganglion neurones. In tonic neurones both subtypes of tachykinin receptors are coupled to membrane depolarization,whereas in phasic neurones activation of these receptors leads to inhibition of LAH. The present study also suggests that NKA evokes the depolarization in tonic neurones and the LAH inhibition in phasic neurones via NK1, but not NK2 receptors.

Animals↗
PubMed1995

Predictive factors in the response to interferon therapy in chronic hepatitis C.

Factors predicting the efficacy of interferon therapy were statistically analyzed on 111 patients with chronic hepatitis C. Of the treated patients (total doses of interferon; 96-468 MU), 35 (31.5%) had a long-term remission. On multivariate analysis, hepatitis C virus genotype (p < 0.0001), histological diagnosis (p < 0.05), fibrosis score of histological activity index (p < 0.01) and source of infection (p < 0.05) were found useful for predicting the response to interferon therapy. Our findings suggest that the outcome of interferon therapy can be predicted to some degree from pretreatment data, and that a new therapeutic strategy is necessary for the group of patients who are predicted to be nonresponders.

Adult↗
PubMed1995

Flagellar filament structure and cell motility of Salmonella typhimurium mutants lacking part of the outer domain of flagellin.

We have isolated spontaneous mutants of Salmonella typhimurium which can swim in the presence of antifilament antibodies. The molecular masses of flagellins isolated from these mutants were smaller than that (52 kDa) of wild-type flagellin. Two mutants which produced the smallest flagellins (42 and 41 kDa) were selected, and the domain structures of the flagellins were analyzed by trypsin digestion and then subjected to amino acid sequencing. The two flagellins have deletions at Ala-204 to Lys-292 and Thr-183 to Lys-279, respectively. These deleted parts belong to the outer domain (D3) of flagellin, which is believed to be at the surface of the filament. These mutant filaments aggregated side by side in the presence of salt, resulting in disordered motility.

Amino Acid Sequence↗
PubMed1995

Use of NK1 receptor antagonists in the exploration of physiological functions of substance P and neurokinin A.

Tachykinin NK1 receptor antagonists were used to explore the physiological functions of substance P (SP) and neurokinin A (NKA). Pharmacological profiles of three NK1 receptor antagonists, GR71251, GR82334, and RP 67580, were examined in the isolated spinal cord preparation of the neonatal rat. These tachykinin receptor antagonists exhibited considerable specificities and antagonized the actions of both SP and NKA to induce the depolarization of ventral roots. Electrical stimulation of the saphenous nerve with C-fiber strength evoked a depolarization lasting about 30 s of the ipsilateral L3 ventral root. This response, which is referred to as saphenous-nerve-evoked slow ventral root potential (VRP), was depressed by these NK1 receptor antagonists. In contrast, the saphenous-nerve-evoked slow VRP was potentiated by application of a mixture of peptidase inhibitors, including thiorphan, actinonin, and captopril in the presence of naloxone, but not after further addition of GR71251. Likewise, in the isolated coeliac ganglion of the guinea pig, electrical stimulation of the mesenteric nerves evoked in some ganglionic cells slow excitatory postsynaptic potentials (EPSPs), which were depressed by GR71251 and potentiated by peptidase inhibitors. These results further support the notion that SP and NKA serve as neurotransmitters producing slow EPSPs in the neonatal rat spinal cord and guinea pig prevertebral ganglia.

Animals↗