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Biomedical subjects

M Shindo

Publications and source records attributed to M Shindo.

At least 109 records · Page 6Linked to original sources
PubMed1997

The clinical value of grading and staging scores for predicting a long-term response and evaluating the efficacy of interferon therapy in chronic hepatitis C.

BACKGROUND/AIMS: To determine the clinical usefulness of a new histological scoring system (grading and staging scores) for predicting a long-term response to interferon therapy and evaluating the efficacy of therapy, we examined biochemical, virological and histological findings during and 1 year after interferon therapy in 109 patients with chronic hepatitis C. METHODS: Hepatitis C virus RNA was assayed by reverse transcriptase polymerase chain reaction, hepatitis C virus genotype was determined by reverse transcriptase polymerase chain reaction using type-specific primers, and histological grading and staging scores were determined according to a newer scoring system. RESULTS: The patients were divided into two groups according to the outcome of serum alanine aminotransferase levels and HCV RNA level during and after therapy: 31 long-term responders whose serum aminotransferase level became and remained normal for 1 year after therapy with undetectable HCV RNA in serum and liver and 78 non-responders whose aminotransferase levels did not normalize during therapy or rose again after therapy. Before therapy, the long-term responders had significantly lower viral levels, lower incidence of genotype 1b, and lower staging scores than those of the non-responders. There was no significant difference in grading score between the long-term and non-responders. Multivariate analysis showed that the viral level and genotype are more important predictors of a long-term response than the staging score. Both grading and staging scores decreased significantly at the end of therapy in both the long-term and non-responders. The 1-year follow-up liver biopsy examination in the long-term responders showed that the grading score, but not the staging score, continued to decrease significantly. CONCLUSIONS: These findings suggest that: (1) the staging score, but not the grading score, appears to be associated with a long-term response, but the viral level and genotype are more important predictors than the staging score; and (2) both the grading and staging scores decreased significantly with interferon therapy, but the staging score appeared to take longer to improve than the grading score.

Alanine Transaminase↗
PubMed1997

Osteogenesis by bone marrow stromal cells maintained on type I collagen matrix gels in vivo.

In this study, we demonstrated that bone marrow stromal cells maintained on type I collagen matrix induced bone in vivo. The formed bone contained bone marrow, and the process of bone formation occurred without cartilage formation. Bone marrow stromal cells differentiated into osteoblasts on type I collagen matrix in vitro, but types II, III, and V collagens did not possess this activity. These findings imply that type I collagen matrix offers a suitable environment for the induction of osteoblastic differentiation in vitro and osteogenesis in vivo.

Alkaline Phosphatase↗
PubMed1997

Dietary red pepper ingestion increases carbohydrate oxidation at rest and during exercise in runners.

The effects of dietary hot red pepper on energy metabolism at rest and during exercise were examined in long distance male runners 18-23 yr of age. A standardized meal was given on the evening prior to the experiment. The subjects had a meal (2720 kJ) with or without 10 g of hot red pepper for breakfast. During rest (2.5 h after meal) and exercise (pedaling for 1 h at 150 W, about 60% VO2max, using cycling ergometry), expired gasses and venous blood were collected. The meal with hot red pepper significantly elevated respiratory quotient and blood lactate levels at rest and during exercise. Oxygen consumption at rest was slightly but nonsignificantly higher in the hot red pepper meal at 30 min after the meal. Plasma epinephrine and norepinephrine levels were significantly higher in those who had only hot red pepper at 30 min after the meal. These results suggest that hot red pepper ingestion stimulates carbohydrate oxidation at rest and during exercise.

Adolescent↗
PubMed1997

Double product response is accelerated above the blood lactate threshold.

Catecholamine concentrations are known to increase sharply in the blood at work rates above the blood lactate threshold (LT); thus, we hypothesized that the double product (DP, heart rate-systolic blood pressure product) may also abruptly increase at work rates above the LT. Ninety healthy students performed a stepwise incremental test on a cycle ergometer. The slopes of the two regression lines below and above the LT for the heart rate (HR), the indirectly measured systolic blood pressure (SBP), and the DP, respectively, were compared using VO2 as an independent variable. For all three parameters the slope of the regression line above the LT was significantly higher than that below the LT. Although either the same or a lower slope was found in the HR (N = 23) or SBP (N = 22) responses in some subjects above the LT as compared with that below the LT, a steeper DP slope above the LT was evident in all 90 subjects. The same results were also obtained during 4-min constant work rate exercise sessions at a variety of submaximal intensities performed in a random order in seven subjects. In addition, we established the DP break point (DPBP) determining protocol with a fairly good test-retest reliability (r = 0.951) and a correlation coefficient between the DPBP and the LT (r = 0.900). These results suggest that the DP increases more steeply above the LT, and, as a result, the DPBP is considered to be a valid and useful parameter as a marker of the LT.

Adult↗
PubMed1997

Central auditory information processing in patients with bilateral auditory cortex lesions.

Severe auditory cognitive disorders in 10 patients who had bilateral lesions either to the auditory cortex and/or auditory radiations were studied audiologically with special attention to residual hearing. This auditory cognitive problem is called "auditory agnosia or cortical deafness". Our study revealed that auditory information processing for pure tones, monosyllable discrimination, environmental sound perception, and auditory comprehension is commonly but differently affected by bilateral lesions of auditory cortex or auditory radiation. In summary, these patients can discriminate loudness of pure tones and some environmental sounds but cannot clearly perceive any sounds of monosyllables and sentences. Generally their residual hearing is useful for auditory awareness and is often enhanced by lip reading.

Adult↗
PubMed1997

Comparison of interaural time and intensity difference discrimination in patients with temporal lobe lesions.

We studied the sound lateralization in 15 patients with left (12 patients) or bilateral (3 patients) temporal lobe cerebrovascular lesions. The lesions included the auditory cortex. Interaural time difference (ITD) and interaural intensity difference (IID) discriminations were separately measured by using a self-recording apparatus. All 12 patients with left temporal lobe lesions could discriminate ITD, and their IID thresholds were significantly higher than those in healthy volunteers. None of the 3 patients with bilateral temporal lobe lesions could discriminate ITD. On the other hand, all patients with either unilateral or bilateral temporal lobe lesions could discriminate IID and their IID thresholds were significantly higher than those in healthy volunteers. The present findings indicate that the auditory cortex plays an important role in discriminating both cues, but that the role may not be essential for IID.

Auditory Cortex↗
PubMed1997

[A case of corticobasal degeneration presenting with primary progressive aphasia].

We report a 64-year-old right-handed woman whose initial symptom was slowly progressive aphasia without generalized dementia and who was subsequently diagnosed as having corticobasal degeneration (CBD). Neurological examination revealed disturbed vertical gaze, dysarthria, rigidity of the right upper extremity, and bilateral instinctive grasp reaction. Neuropsychological assessment disclosed Broca's aphasia, buccofacial apraxia, and memory disturbance. MRI of the brain showed atrophy of the frontotemporal lobes, which was more severe on the left than on the right, especially the left inferior frontal gyrus. In most reported cases of CBD, the initial symptom is motor dysfunction of the unilateral upper or lower extremity. However, we should be cautious that among cases with CBD, there have been rare cases that begin with progressive aphasia alone. In our case, the atrophied region of the cerebral cortex was most severe around the left inferior frontal gyrus. In a few reported cases with the initial symptom of aphasia, the atrophied region corresponded considerably to the type of the aphasia. On the other hand, in those whose initial symptom was mainly motor dysfunction of the unilateral extremity, the atrophied region was remarkable in the posterior part of the frontal lobe and parietal lobe. Therefore, we suggest that in CBD the distribution of the cerebral cortical lesions differs in accordance with whether the initial symptom is motor disturbance or aphasia, and that the type of aphasia corresponds to the location of the cortical lesion.

Aphasia, Broca↗
PubMed1996

Sound lateralization in patients with lesions including the auditory cortex: comparison of interaural time difference (ITD) discrimination and interaural intensity difference (IID) discrimination.

We examined sound lateralization using dichotic presentation of noises in 15 patients with left unilateral (12 patients) or bilateral (3 patients) temporal lobe lesions, that included the auditory cortex, and evaluated their abilities to discriminate interaural time and intensity difference (ITD, IID) separately. On the ITD discrimination test, discrimination thresholds in patients with left unilateral lesions were significantly higher than those in normal subjects, but all patients with left unilateral lesions could detect ITD. However, none of 3 patients with bilateral lesions could detect ITD. On the IID discrimination test, all patients with either unilateral or bilateral lesions could detect IID. IID discrimination thresholds in these patients were significantly higher than those in normal subjects. The auditory cortex plays an important role in discriminating both cues, but appears to be necessary for discriminating ITD.

Adolescent↗
PubMed1996

Inhibitory projection from brachioradialis to biceps brachii motoneurones in human.

Neural projection from the brachioradialis to the biceps brachii motoneurones in human was studied using the method of post-stimulus time histogram. Electrical stimulation to the radial branch innervating the brachioradialis produced inhibition in 11 out of 21 biceps motor units. The central delays of the inhibition were 0.7-1.2 ms longer than those of the homonymous facilitation. The inhibition was evoked with the intensity below the motor threshold. Pure cutaneous stimulation provoked no effects on the motor-unit firing. These findings suggest that group I afferents from the brachioradials mediate an oligosynaptic inhibition of the biceps brachii motoneurones.

Adult↗
PubMed1996

Induction mechanism of small intestinal lesions caused by intravenous injection of endotoxin in rats.

The pathogenesis of intestinal damage caused by bolus intravenous injection of endotoxin (ETX; 3 mg/kg) was investigated. Administration of ETX to rats induced reddish discoloration suggestive of bleeding, increased hemoglobin amounts, and leakage of plasma protein in the intestine. However, light microscopic examination of the intestine demonstrated blood congestion of the microvessels. Plasma accumulation was partially inhibited by combined pretreatment with a histamine H1 antagonist and a serotonin (5-HT) antagonist. Neither a 5-lipoxygenase inhibitor, a soybean trypsin inhibitor, nor atropine was observed to inhibit plasma accumulation. Both the intestinal leakage of plasma and the accumulation of hemoglobin were completely inhibited by indomethacin, a selective thromboxane A synthetase inhibitor (OKY 1581), and a stable PGI2 analogue (beraprost). Intravital microscopic observation of the microvessels of the small intestinal villi demonstrated microthrombus formation within several minutes after the injection of ETX, and pretreatment with OKY 1581 attenuated the formation of microthrombus. Platelet counts decreased significantly 10 min after ETX administration, and the decrease was not inhibited by pretreatment with either OKY 1581 or beraprost. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were not prolonged. These observations thus suggest that microcirculatory disturbances by platelet thrombus, which are mediated by thromboxane A2 at least in part, play an important role in ETX-induced intestinal damage.

Animals↗
PubMed1996

Characterization of whole cell chloride conductances in a mouse inner medullary collecting duct cell line mIMCD-3.

The chloride conductance of inner medullary collecting duct cells (mIMCD-3 cell line) has been investigated using the whole cell configuration of the patch clamp technique. Seventy-seven percent of cells were chloride selective when measured with a NaCl-rich bathing solution and a TEACl-rich pipette solution. Seventy-five percent of chloride-selective cells (90/144) had whole cell currents which exhibited an outwardly-rectifying (OR) current-voltage (I/V) relationship, while the remaining cells exhibited a linear (L) I/V relationship. The properties of the OR and L chloride currents were distinct. OR currents (mean current densities at +/- 60 mV of 66 +/- 5 pA/pF and 44 +/- 3 pA/pF), were time- and voltage-independent with an anion selectivity (from calculated permeability ratios) of SCN- (2.3), NO3- (1.8), ClO4- (1.7), Br- (1.7), I- (1.6), Cl- (1.0), HCO3- (0.5), gluconate- (0.2). Bath additions of NPPB, flufenamate, glibenclamide (all 100 microM) and DIDS (500 microM) produced varying degrees of block of OR currents with NPPB being the most potent (IC50 of approximately 50 microM) while DIDS was the least effective. Linear chloride currents had similar current densities to the OR chloride currents and were also time- and voltage-independent. The anion selectivity sequence was SCN- (2.5), NO3- (1.9), Br- (1.4), I- (1.1), Cl- (1.0), ClO4- (0.5), HCO3- (0.5), gluconate- (0.3). In contrast to the OR conductance, glibenclamide was the most potent and DIDS the least potent blocker of L currents. An IC50 of > 100 microM was observed for NPPB block. Neither OR of L chloride currents were affected by acutely or chronically increased intracellular cAMP and were not affected when intracellular Ca2+ levels were increased or decreased. The molecular identity and physiological role of OR and linear currents in mIMCD-3 cells are discussed.

Animals↗
PubMed1996

Impaired non-insulin mediated glucose uptake after downhill running in rats.

To evaluate the effects of a single bout of exercise on non-insulin mediated glucose uptake in rats, hyperglycemic clamp tests were performed either 12 h after the rats were subjected to downhill running (90 min, -16 degrees incline, n = 10) or without any prior exercise (n = 10). Somatostatin (1.0 microgram/kg/min) was infused during clamps to suppress insulin secretion, while the serum glucose was clamped at a level of 200 mg/dl for 100 min. The serum insulin levels during the hyperglycemic clamp was maintained at basal levels. The non-insulin mediated glucose disposal rate was significantly decreased during clamp performed after downhill running (5.45 +/- 0.61 mg/kg/min) compared to the control conditions (9.63 +/- 0.32 mg/kg/min, P < 0.01). The creatine kinase level after downhill running (561 +/- 206 IU/l) was significantly higher than the control conditions (118 +/- 20 IU/l, P < 0.01). These results thus suggest that the muscle damage caused by downhill exercise, which predominantly consists of eccentric type, may therefore decrease the non-insulin mediated glucose uptake.

Animals↗
PubMed1996

Cytokine mRNA expression in the liver of patients with primary biliary cirrhosis (PBC) and chronic hepatitis B (CHB).

The expression of cytokine mRNA species was determined in liver biopsies from six normal subjects, 18 patients with PBC and 14 patients with hepatitis B e antigen (HBeAg)-positive CHB using a reverse transcriptase-polymerase chain reaction (RT-PCR) technique. cDNA, obtained by reverse transcription using oligo d(T) primers, was amplified by PCR using primers specific for the coding region of seven different cytokines (IL-1, IL-2, IL-4, IL-5, IL-6, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha)). The abundance of some cytokines (IL-2, IL-4, IL-5 and IFN-gamma) was also estimated by semiquantitative RT-PCR, using as standards dilutions of synthetic cytokine mRNA transcripts, that could be distinguished electrophoretically from respective native cytokine mRNAs. Hepatic inflammation was assessed by a semiquantitative histologic score and by amplification of mRNA for T cell receptor (TCR)-alpha. mRNAs for IL-1 and IL-6 were detected in only one control liver. In CHB, mRNAs for IL-1, IL-2, IL-4, IL-5 and IFN-gamma were detected in 43%, 60%, 80%, 20%, and 54% of biopsies, respectively. mRNA for IFN-gamma and IL-4, but not IL-1, tended to be associated with severe inflammation. In five biopsies semiquantitative analyses revealed increased levels of mRNA for TCR-alpha and, when transcripts were detectable, high levels of mRNA for IFN-gamma and IL-4. In PBC, mRNA for IFN-gamma was detected in 60% of biopsies, but no mRNAs for IL-1, IL-2, IL-4, IL-5, or IL-6, or for TNF-alpha, were detected. Semiquantitative analyses revealed that absolute levels of mRNA for IFN-gamma tended to correlate with the severity of hepatic inflammation. The results suggest that: (i) there may be fundamental differences in the roles that cytokines play in the hepatic inflammatory processes of PBC and CHB; and (ii) while hepatic IFN-gamma mRNA expression is not specific for PBC, IFN-gamma may play a prominent role in the immunopathogenesis of PBC.

Adult↗
PubMed1996

The clinical significance of changes in genetic heterogeneity of the hypervariable region 1 in chronic hepatitis C with interferon therapy.

We examined changes in the hypervariable region 1 of the hepatitis C virus (HCV) RNA that occurred with interferon therapy in 33 patients with chronic hepatitis C to assess the clinical significance of this region. The 33 patients had HCV genotype 1b and were classified into three groups based on serum aminotransferase levels during and after therapy with alpha interferon; long-term responders (n = 9), short-term responders (n = 11), and nonresponders (n = 13). Changes in the genetic heterogeneity of the hypervariable region 1 were determined by using nonisotopic polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). HCV RNA levels were evaluated by reverse transcriptase PCR and branched DNA probe assays. Changes in sequences were determined by cloning and sequencing analysis. Before therapy, the long-term responders had significantly lower degrees of heterogeneity and lower viral levels than nonresponders. There were no significant differences between short-term and nonresponders. With interferon therapy, viral levels and degree of heterogeneity decreased to a greater extent among long-term and short-term responders than among nonresponders. Sequencing analysis showed that the three groups had similar clone numbers initially, but long-term responders had rather homogeneous viral populations, whereas short-term and nonresponders had heterogeneous populations, but that there were no nucleotide sequences or amino acid alignments that were specific for any group before, during, and 6 months after therapy. Approximately half of short-term and nonresponders received a second course of interferon 7 to 10 months after the initial therapy; all showed an identical response to the second course of therapy regardless of interim changes in the heterogeneity of hypervariable region 1. These findings suggest that (1) patients who were nonresponders or short-term responders had mixed viral populations that had differing sensitivities to interferon, (2) the changes in the hypervariable region 1 (HVR 1) did not affect responsiveness to interferon, and (3) the lower heterogeneity in the HVR 1 was associated with a long-term response to interferon only when the viral levels were low.

Chronic Disease↗
PubMed1996

Effects of a single bout of exercise on glucose effectiveness.

The effects of a single bout of exercise on glucose effectiveness (SG) and insulin sensitivity (SI) in 22 sedentary subjects were estimated with a minimal model approach. The intravenous glucose tolerance test (IVGTT) was performed 1) 11 h after an exercise bout on a cycle ergometer at the lactate threshold level (mild exercise) for 60 min, 2) 11 h after an exercise bout at the 4 mM lactate level (hard exercise) for 36 +/- 1 min, 3) 11 h after an exhaustive-exercise bout (exhaustive exercise) for 96 +/- 7 min, or 4) without any prior exercise (control). Only the exhaustive exercise increased the glucose disappearance constant (2.69 +/- 0.28 vs. 2.05 +/- 0.13%/min; P < 0.05) and SI (15.0 +/- 2.0 vs. 10.3 +/- 0.9 x 10(-5) min/pM: P < 0.05) in comparison with the control condition. The SG and SG at zero insulin (GEZI) were not affected by any exercise condition. However, a marked individual difference in GEZI emerged after the exhaustive exercise and could be divided into two subgroups: one decreased in GEZI (0.014 +/- 0.001 vs. 0.007 +/- 0.001 min-1) and the other increased in GEZI (0.014 +/- 0.001 vs. 0.021 +/- 0.003 min-1). The former subgroup was accompanied by elevated levels of plasma creatine kinase (100 +/- 16 vs. 598 +/- 315 IU/l; P < 0.05) and myoglobin (Mb; 46 +/- 4 vs. 126 +/- 47 ng/ml; P < 0.05), whereas the latter subgroup showed no significant change in creatinine kinase (99 +/- 10 vs. 128 +/- 9 IU/l; P > 0.05) and Mb (50 +/- 7 vs. 51 +/- 4 ng/ml; P > 0.05). In both subgroups, SI was similarly increased after the exhaustive exercise. These results thus suggest that a single bout of exercise that results in muscle damage or changes in muscle permeability, as reflected in the increased creatine kinase and Mb levels, decreases GEZI, whereas exhaustive exercise without such alterations increases GEZI.

Adult↗
PubMed1996

Abnormalities of ABR and auditory perception test findings in acquired palatal myoclonus.

An auditory test battery consisting of pure tone audiometry, the auditory brainstem response (ABR), the nonsense monosyllable perception test, the dichotic listening test and the Token test were administered to three patients with palatal myoclonus. All patients had ABR abnormalities correlated with the location of brainstem lesions, despite relatively normal pure-tone threshold. In two of the three patients, both the nonsense monosyllable test and the dichotic listening test revealed dominance on the side ipsilateral to the lesion, while ABR abnormalities were present on the contralateral side. In one patient who had bilateral ABR abnormalities, both the monosyllable perception and dichotic listening test scores were poor for bilateral ears. These results suggest that brainstem lesions producing palatal myoclonus could have an effect on auditory perception.

Adult↗
PubMed1996

Auditory nerve disease of both ears revealed by auditory brainstem responses, electrocochleography and otoacoustic emissions.

We report on two patients who showed absence of auditory brainstem response (ABR) but broad compound action potentials on electrocochleograms and almost normal otoacoustic emissions, together with absence of caloric response and preservation of per rotatory nystagmus for both ears. Patient 1, a 53-year-old woman, had noted auditory and vestibular problems since the age of 15 years, and Patient 2, a 68-year-old woman, had noted problems of the same age of 30 years. They could hear words and understand sentences if spoken slowly, but they could not discriminate monosyllables very well. Their auditory examinations disclosed mild threshold elevation in pure-tone audiometry and markedly poor scores in speech audiometry and good scores in auditory comprehension test. They were diagnosed as having auditory nerve disease of unknown cause.

Acoustic Stimulation↗