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Biomedical subjects

K Yoshioka

Publications and source records attributed to K Yoshioka.

At least 289 records · Page 16Linked to original sources
PubMed1994

Changes in serum hepatitis C virus RNA titer and response to interferon therapy in patients with chronic hepatitis C.

Response to interferon (IFN) therapy for chronic hepatitis C has been determined by the alteration of serum alanine aminotransferase (ALT) values. However, eradication of hepatitis C virus (HCV) could be another aim of the therapy. Thus, we serially measured serum HCV RNA levels during therapy and for at least 12 months after cessation of therapy in 65 patients with chronic hepatitis C who received IFN-alpha (49 cases) or -beta (16 cases). The presence of HCV and its amount were measured by the combination of nested and competitive PCR. Twenty-seven patients, who were categorized as complete responders, showed sustained normalization of ALT values for more than six months posttreatment. The viral RNA titers at pretreatment were significantly lower in complete responders (logarithmic copy numbers/ml: 5.4 +/- 1.3, P < 0.001) than in partial and nonresponders. Complete response rate was significantly higher in patients with HCV genotype III (68.4%, P < 0.01) than those with type II (23.6%). Among 27 complete responders, HCV RNA became undetectable in only 13 patients six months after completion of therapy, and 11 still had low levels of viremia; however, none experienced relapse of the disease during follow-up of 12-24 months. Three complete responders showed lasting high-titered viremia, and their ALT values rose again during follow-up. Our data suggest that IFN treatment of chronic hepatitis C is often ineffective in eradicating HCV infection even in responders, and long-term follow-up study is necessary to determine the sustained beneficial effect of IFN.

Adult↗
PubMed1994

Evaluation of a nine-lead Holter monitor for identifying and localizing ischemia and coronary artery disease detected by quantitative thallium-201 tomography.

We devised a nine-lead Holter monitor system with a lead-switching technique to record electrocardiograms from multiple sites in the anterior and the posterior or lateral chest. Leads CM1 to CM6, high lateral (HL), low lateral (LL), and low posterior chest (LB) were used. The sensitivity, specificity, and predictive accuracy of this system for identifying specific regions of myocardial ischemia and coronary artery disease were investigated in 130 patients with coronary artery disease. Anterolateral leads (CM4 to CM6, HL, and LL) showed high sensitivity for detecting anterior and lateral ischemia (69% to 100%) but low specificity (4% to 44%) compared with tomographic results. The specificity of these leads for identifying single-vessel disease was low (6% to 47%) although some leads showed high sensitivity (69% to 100%). In contrast, the LB lead exhibited high sensitivity and specificity for detecting inferior ischemia (70% and 95%, respectively) and right coronary artery (RCA) disease (74% and 93%, respectively). Consequently, ST depressions in the LB lead (anode) are specific for identifying inferior ischemia and RCA disease, whereas those in the anterior and lateral chest leads do not identify the ischemic region or the obstructed coronary artery.

Coronary Angiography↗
PubMed1994

Regional sympathetic denervation detected by iodine 123 metaiodobenzylguanidine in non-Q-wave myocardial infarction and unstable angina.

Previous studies have revealed that the sympathetic nervous system is more vulnerable to ischemia than the myocardium itself. Thus our study was undertaken to detect denervated myocardium in non-Q-wave myocardial infarction (MI) and unstable angina with iodine 123 metaiodobenzylguanidine (123I-MIBG), which can delineate myocardial sympathetic innervation. Eight patients with non-Q-wave MI and 12 with unstable angina were studied. Sequential 123I-MIBG and thallium-201 chloride (201TlCl) imaging and single-photon emission computed tomography (SPECT) were performed at rest 24 +/- 12 days after the last ischemic attack. Myocardial perfusion defect was not detected by 201TlCl in 4 of 8 patients with non-Q-wave MI, whereas 123I-MIBG SPECT imaging revealed defects corresponding to myocardial ischemic areas predicted by coronary angiography in all 8 patients. 123I-MIBG imaging revealed defects in 7 of 12 patients with unstable angina corresponding to coronary angiographic findings, whereas no myocardial perfusion defect was detected by 201TlCl imaging in any of them. In conclusion, 123I-MIBG SPECT is a sensitive method for detecting myocardium exposed to transient ischemia that cannot be detected by 201TlCl imaging.

3-Iodobenzylguanidine↗
PubMed1994

PCR and immunoblot analyses of dystrophin in Becker muscular dystrophy.

The dystrophin gene was examined by PCR analysis in 30 Japanese patients with Becker muscular dystrophy (BMD). Fifteen PCR of these patients had exon deletion, generally, less than three exons. Muscle biopsies were also performed in 20 BMD patients (10 with sequence deletions, and 10 without detectable sequence deletions) in order to correlate PCR findings with immunoblot and immunostaining data. A patchy, heterogeneous membrane immunostaining pattern of reduced intensity was found, irrespective of the presence or absence of deletions. Immunoblotting studies demonstrated dystrophin of low molecular mass and quantity in BMD patients with deletion mutations, while a low quantity of dystrophin with an apparent wild type molecular mass was observed in nearly half the BMD patients without detectable deletions. However, these dystrophins were also found to have slightly abnormal molecular masses when the standard electrophoresis time was prolonged. This suggests that immunoblots and PCR data correlate well in patients with BMD. Additionally, it is suggested that immunoblot assays can detect abnormalities in dystrophin in the absence of detectable PCR deletions.

Adolescent↗
PubMed1994

Relationship between diabetic autonomic neuropathy and peripheral neuropathy as assessed by power spectral analysis of heart rate variations and vibratory perception thresholds.

To investigate the relationship between diabetic autonomic and peripheral neuropathies, we carried out power spectral analysis (PSA) of heart rate variations and determined the vibratory perception threshold (VPT) in diabetic subjects (DM). The VPT, measured with a Suzuki-Matsuoka Vibrometer (SMV-5), was greater in diabetic subjects than in controls. The low frequency (LF) component of the PSA which represents sympathetic nervous activity and the high frequency (HF) component of the PSA which indicates parasympathetic nervous activity were significantly decreased in diabetic subjects when compared to values in the controls. In addition, there were significant inverse correlations between the LF and HF components of the PSA of heart rate variations and the VPT. These results suggest that the PSA of heart rate variations and the measurement of VPT are useful tools for evaluating diabetic autonomic and peripheral neuropathies.

Autonomic Nervous System↗
PubMed1994

Carrier-mediated transport of H1-antagonist at the blood-brain barrier: mepyramine uptake into bovine brain capillary endothelial cells in primary monolayer cultures.

The transport mechanism of the H1-antagonist mepyramine at the blood-brain barrier (BBB) was studied by using primary cultured monolayers of bovine brain capillary endothelial cells (BCEC). The initial uptake of [3H]mepyramine into the BCEC showed strong temperature and concentration dependency, indicating that it involves both saturable and nonsaturable processes. Transport at the luminal membrane may be the rate-limiting process in the transcellular transport, since the values of the uptake coefficient of [3H]mepyramine at the luminal membrane (609 microliters/mg protein/min) and the transcellular permeability coefficient (488 microliters/mg protein/min) are very similar. The initial uptake of [3H]mepyramine was not affected by metabolic inhibitors, but was stimulated by preloading with the drug. Mepyramine appears to be transported into the BCEC by a carrier-mediated transport system which does not require metabolic energy, probably via a facilitated diffusion mechanism.

Animals↗
PubMed1994

Carrier-mediated transport of H1-antagonist at the blood-brain barrier: a common transport system of H1-antagonists and lipophilic basic drugs.

The blood-brain barrier (BBB) transport system for H1-antagonists was studied using primary cultured bovine brain capillary endothelial cells (BCEC). The uptake of [3H]mepyramine was inhibited by various H1-antagonists. Ketotifen competitively inhibited [3H]mepyramine uptake with an inhibition constant (Ki) of 46.8 microM. Lipophilic basic drugs such as propranolol, lidocaine and imipramine significantly inhibited [3H]mepyramine uptake. In particular, propranolol inhibited [3H]mepyramine uptake competitively at an inhibition constant (Ki) of 51.1 microM. Moreover, in ATP-depleted BCEC, [3H]mepyramine uptake was stimulated by preloading with H1-antagonists and lipophilic basic drugs. These results indicated that H1-antagonists are transported across the BBB via a carrier-mediated transport system common to lipophilic basic drugs.

Animals↗
PubMed1994

Localization of the complement regulatory proteins in the normal human kidney.

The kidney is an organ where complement-mediated tissue injuries take place by various stimuli. To assess how the kidney is protected from the autologous complement attack, comparative localization of decay accelerating factor (DAF), membrane cofactor protein (MCP) and 20 kDa homologous restriction factor (HRF20) was studied in the normal human kidney. Specific monoclonal antibodies to DAF, MCP and HRF20 were used for the study. Studies by immunofluorescence and immunoelectron microscopy showed that the distribution of each protein in the kidney was complementary to each other in most parts. MCP and HRF20 were clearly seen in the glomerular capillaries, while DAF was only faintly observed. Juxtaglomerular apparatus was abundant in DAF and MCP but not in HRF20. HRF20 was most strongly expressed in the peritubular capillaries where MCP was not detectable. Basolateral membranes of the proximal tubules and collecting ducts expressed MCP strongly, while there was no expression of DAF in the proximal tubules. Interestingly, both DAF and MCP, which inhibit complement activation at C3/C4 level, were not expressed in the apical portion of the tubular cells including proximal tubule brush border. In contrast, HRF20 was expressed on the apical part of the tubules. Medullary interstitium strongly expressed MCP but not DAF. Based on these observations, we conclude that each segment of the kidney is protected from the complement attack by the different combination of complement regulatory proteins. We speculate that the tubular cells might be fragile when complements are activated inside the tubular lumen, because there is no expression of complement regulatory proteins which inhibit C3 convertase.

Antibodies, Monoclonal↗
PubMed1994

Mutations in the COL4A5 gene in Alport syndrome: a possible mutation in primordial germ cells.

Using a combination of gene amplification with single strand conformation polymorphisms analysis and sequencing, we examined the COL4A5 gene in 37 patients with Alport syndrome. In patient A8, a single base insertion was noted at codon 1,597 tyrosine in exon 49. The premature terminal signal appeared and 89 amino acids (approximately one-third) of the non-collagenous domain were lost. The mutation was present in the mother, hence she is heterozygous. In patient A12, the nucleotide changed from C to T at codon 1,679 glutamine in exon 51, which created a termination codon, and 7 amino acids at the carboxyl terminus were lost. Gene tracking using peripheral leukocytes revealed that the parents did not carry the mutant allele, while the sister was heterozygous. DNA samples from hair roots and skin fibroblasts of the mother were normal and immunological examination of the epidermis of the mother indicated that the alpha 5(IV) chain was normally expressed. As these results suggest that somatic cells of the mother do not carry the mutant allele, the primordial germ cells possibly carry a fresh mutation in the mother of patient A12.

Adolescent↗
PubMed1994

Immunohistochemical study of alpha 1-5 chains of type IV collagen in hereditary nephritis.

The distribution of alpha 1-5 chains of type IV collagen [alpha 1-5(IV)] in the glomerular basement membrane (GBM) and epidermal basement membrane (EBM) of 23 families with hereditary nephritis was examined by indirect immunofluorescence. These families were divided into three clinicopathological groups. Group I (10 families) patients showed a widespread "basket weave" pattern of the GBM and a family history of nephritis was present. Group II (6 families) patients showed a widespread "basket weave" change without a family history of nephritis. Group III (7 families) patients showed a widespread attenuation of the GBM but no "basket weave" change, and had a family history of nephritis and chronic renal failure. alpha 1(IV) and alpha 2(IV) were present in all affected and unaffected family members and controls. All normal family members and controls expressed alpha 3(IV), alpha 4(IV) and alpha 5(IV) in the GBM and alpha 5(IV) in the EBM in a diffuse pattern. All group I families and three of the group II families exhibited complete loss of the alpha 5(IV) antigen from the GBM and EBM in male patients, and segmental loss of the alpha 5(IV) antigen in female patients. In these families the alpha 3(IV) and alpha 4(IV) antigens were completely lost from the GBM in male patients with severe nephritis, whereas alpha 3(IV) alpha 4(IV) were present but diminished in male patients with mild nephritis. Three group II and all group III families expressed the alpha 3-5(IV) antigens in an identical manner to that of normal controls. These findings indicate that the heterogeneity of hereditary nephritis reflects a variety of aberrant expression patterns of alpha 3-5(IV) and that immunohistochemical examination of alpha 5(IV) in the EBM is a useful method for the diagnosis of X-linked Alport syndrome.

Adult↗
PubMed1994

Effects of sympathetic stimulation, with and without previous alpha 1 and beta adrenoceptor blockade, on refractoriness dispersion in canine heart.

OBJECTIVE: The aim was to determine the electrophysiological effects of cardiac sympathetic stimulation, with and without prior alpha 1 and beta adrenoceptor blockade during myocardial ischaemia in dogs. METHODS: Chloralose anaesthetised dogs were studied 2 h after ligation of the obtuse marginal branches of the circumflex artery (OMB). The refractory period was measured at eight sites in the ischaemic zone, two sites in the border zone, and two sites in the normal zone with S1-S2 extrastimulus methods. RESULTS: In group 1 (n = 13), before OMB ligation, stimulation of the ventrolateral cardiac nerve shortened the refractory period only in the ischaemic zone (p < 0.01). OMB ligation resulted in a significant shortening of the refractory period in the ischaemic zone (p < 0.01). In group 2 (n = 12), the alpha 1 blocker bunazosin (0.2 mg.kg-1, intravenously) blunted the shortening of the refractory period in the ischaemic zone induced by OMB ligation (p < 0.01), resulting in a reduction in refractory period dispersion between the ischaemic and non-ischaemic (border and normal) zones. Subsequent administration of the beta blocker propranolol (0.2 mg.kg-1, intravenously) prolonged refractory periods both in the ischaemic and in the non-ischaemic zones (p < 0.05 v p < 0.001). Ventrolateral cardiac nerve stimulation reversed the effects of bunazosin on the refractory period in the ischaemic zone; however, after the addition of propranolol, neural stimulation no longer influenced the refractory period. In group 3 (n = 13), propranolol (0.2 mg.kg-1, intravenously) reversed the shortening of the refractory period in the ischaemic zone (p < 0.01) induced by OMB ligation but also prolonged the refractory period in the non-ischaemic zone (p < 0.001); refractory period dispersion between the ischaemic and non-ischaemic zones was thus not reduced. Ventrolateral cardiac nerve stimulation had no effect on refractory period after administration of propranolol alone or propranolol followed by bunazosin. CONCLUSIONS: Although an alpha 1 blocker may be better than a beta blocker in reducing refractory period dispersion between the ischaemic and non-ischaemic myocardium, a beta blocker may protect more effectively than an alpha 1 blocker against the detrimental effects of cardiac nerve activity on electrical instability in the ischaemic myocardium.

Adrenergic alpha-Antagonists↗
PubMed1994

The augmented rectal bladder for urinary diversion: experience with the original valved rectum and a valve-less modification.

Kock's augmented and valved rectum was created in 10 patients following total cystectomy. During an observation period of up to 46 months, 4 patients died (1 from a recurrence of cancer, 1 from multiple organ failure subsequent to diabetes mellitus, 1 from coronary insufficiency, and 1 from cerebral hemorrhage). Post-operative complications included valve failure in 1, hydronephrosis in 2, and mild nocturnal urinary incontinence in another. Hyperchloremic metabolic acidosis was particularly notable in the cases without an intussuceptive valve of the rectum. Their base excess ranged from -6.9 to -15.0 mM/l but the condition was satisfactorily controlled by oral administration of alkaline agents. Although the present method has a number of shortcomings, the absence of a stoma and elimination of the need for self-catheterization are outstanding benefits. For these reasons, we believe that it is an effective option for urinary diversion.

Aged↗
PubMed1994

Localization of fibril/microfibril and basement membrane collagens in diabetic glomerulosclerosis in type 2 diabetes.

Collagen is one of the major components of the extracellular matrices of the kidney. Basement membrane collagen, type IV collagen, is the major component in normal glomeruli. Fibril and interstitial collagen such as type III collagen, type V collagen, and type VI collagen are minor components of glomerular extracellular matrices and are localized mainly in the interstitium. Diabetic glomerulosclerosis is characterized by the expansion of the glomerular mesangial matrix as well as by thickening of the glomerular basement membrane. In order to clarify the roles of these various types of collagen in the development of diabetic glomerulosclerosis, immunohistochemical studies were performed in kidney specimens from patients with Type 2 diabetes. Early glomerulosclerosis is characterized by expansion of mesangial matrix with basement membrane collagen. However, in later stages glomerulosclerosis is characterized by an increase in the minor collagen components, such as type V and type VI collagen or collagens not normally present, such as type III collagen. Mesangial cells are known to synthesize all these types of collagen. In diabetes, phenotypic change in mesangial cells might produce excess amounts of fibril and interstitial collagen such as type III, type V, and type VI collagen, thus, leading to glomerulosclerosis.

Aged↗
PubMed1994

Involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters in neonatal rat spinal cord.

1. The possible involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters was examined in the spinal cord of the neonatal rat. 2. The magnitude of substance P (SP)- or neurokinin A (NKA)-evoked depolarization of a lumbar ventral root in the isolated spinal cord preparation was increased by a mixture of peptidase inhibitors, consisting of actinonin (6 microM), arphamenine B (6 microM), bestatin (10 microM), captopril (10 microM) and thiorphan (0.3 microM). The mixture augmented the response to NKA more markedly than that to SP. 3. In the isolated spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow depolarization of the L3 ventral root was augmented by the mixture of peptidase inhibitors in the presence of naloxone (0.5 microM) but not in the presence of both naloxone and a tachykinin receptor antagonist, GR71251 (5 microM). 4. Application of capsaicin (0.5 microM) for 6 min to the spinal cord evoked an increase in the release of SP from the spinal cord. The amount of SP released was significantly augmented by the mixture of peptidase inhibitors. 5. Synaptic membrane fractions were prepared from neonatal rat spinal cords. These fractions showed degrading activities for SP and NKA and the activities were inhibited by the mixture of peptidase inhibitors. The degrading activity for NKA was higher than that for SP and the inhibitory effect of the mixture for NKA was more marked than that for SP. Although some other fractions obtained from homogenates of spinal cords showed higher degrading activities for SP, these activities were insensitive to the mixture of peptidase inhibitors. 6. Effects of individual peptidase inhibitors on the enzymatic degradation of SP and NKA by synaptic membrane fractions were examined. Thiorphan, actinonin and captopril inhibited SP degradation, while thiorphan and actinonin, but not captopril, inhibited NKA degradation. The potency of the inhibition of each peptidase inhibitor was lower than that of the mixture.7. The present results suggest that enzymatic degradation is involved in the inactivation of tachykinin neurotransmitters in the spinal cord of the neonatal rat.

Animals↗
PubMed1994

Effects of RP 67580, a tachykinin NK1 receptor antagonist, on a primary afferent-evoked response of ventral roots in the neonatal rat spinal cord.

1. The pharmacological characteristics of RP 67580, a non-peptide tachykinin NK1 receptor antagonist, and its effects on a reflex response evoked by stimulation of primary afferent fibres, were examined in isolated neonatal spinal cord preparations of the rat. Potentials were recorded extracellularly from a lumbar ventral root and drugs were bath-applied in normal artificial cerebrospinal fluid (CSF) or in the presence of tetrodotoxin (TTX). 2. In normal artificial CSF, RP 67580 (0.1-0.3 microM) caused rightward shifts of the concentration-response curves for substance P (SP), neurokinin A (NKA) and substance P methyl ester (SPOMe), an NK1-selective agonist, with pA2 values of 7.25, 7.47 and 7.49, respectively. 3. In the presence of TTX (0.3 microM), RP 67580 also caused rightward shifts of the concentration-response curves for SPOMe and NKA. The pA2 value of RP 67580 against SPOMe (6.75) was significantly lower than that against NKA (7.22). RP 67580 (0.3-1 microM) did not cause a clear parallel shift of the concentration-response curves for SP, and it depressed the depolarizations induced by low concentrations of SP, but slightly potentiated those induced by high concentrations of SP. 4. RP 67580 (1 microM) did not depress the depolarizing responses to bombesin, L--glutamate, gamma-aminobutyric acid (GABA), thyrotropin-releasing hormone and muscarine. RP 67580 (1 microM), however, depressed the response to acetylcholine in the presence of atropine and the response to nicotine. RP 68651 (1 microM), the enantiomer of RP 67580 devoid of activity at tachykinin NK1 receptors, also depressed the response to acetylcholine in the presence of atropine. 5. RP 67580 (1 gAM) did not induce GABA release from the rat spinal cord.6. In the neonatal gerbil spinal cord, the antagonist effects of RP 67580 (0.3-1 JAM) against SPOMe were much less potent than in the neonatal rat spinal cord.7. In the rat spinal cord-saphenous nerve preparation, electrical stimulation of the saphenous nerve atC-fibre strength evoked a prolonged depolarization of the ipsilateral L3 ventral root (slow VRP).RP 67580 (0.1-1 JM) depressed the saphenous nerve-evoked slow VRP. In contrast, RP 68651 (0.3 JAM)had no effect on the slow VRP.8. The results of the present study indicate that RP67580 acts as a high affinity NK, receptor antagonist in the neonatal rat spinal cord, although it also possesses an antinicotinic action. This study further suggests the existence of a subpopulation of tachykinin NK, receptors that are activated by NKA and SPOMe, as well as by low concentrations of SP, and are sensitive to the antagonist action of RP 67580 in the neonatal rat spinal cord. This study also provides further evidence for the involvement of SP and NKA in the slow VRP evoked by C-fibre stimulation in the neonatal rat spinal cord.

Animals↗
PubMed1994

Localisation and characterisation of dystrophin in the central nervous system of controls and patients with Duchenne muscular dystrophy.

The aim was to localise and characterise dystrophin in various human tissues, especially in the CNS. Immunoblotting and immunostaining studies were carried out with eight region-specific dystrophin antibodies. In necropsy tissue from controls, dystrophin was noted as a doublet in immunoblots of striated muscle, and as a single band in those of smooth muscle and the CNS. With immunostaining, punctate immunoreactivity was seen on the cell bodies and dendrites of the cerebral cortical neurons and cerebellar Purkinje cells. By contrast, dystrophin was not detected in any tissues, including the cerebrum and cerebellum, of patients with Duchenne muscular dystrophy who had an intellectual disturbance.

Adolescent↗