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Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 109 records · Page 6Linked to original sources
PubMed2000

Increased rate of formation of small-sized platelet aggregates in patients with acute coronary syndromes.

Coronary thrombosis has been implicated in the pathogenesis of acute coronary syndromes, and platelet activation plays a pivotal role in the pathogenesis of coronary thrombus. A new platelet aggregometer using a laserlight scattering beam was trialled for assessment of platelet aggregation. Platelet aggregability, especially small-sized platelet aggregates, was investigated on admission using the laser-light scattering method and again after treatment in 23 patients with acute coronary syndromes. The platelet aggregability in 14 patients with stable exertional angina and in 14 control subjects was also examined. On admission, the number of small- and medium-sized platelet aggregates in the acute coronary syndromes group was significantly greater than in the stable exertional angina group or control group. However, the number of large-sized platelet aggregates on admission was not increased in the acute coronary syndromes group. Furthermore, the number of small- and medium-sized platelet aggregates decreased significantly after treatment in the acute coronary syndromes group. The increased number of small-sized platelet aggregates may sensitively reflect attacks of thrombosis in patients suffering acute coronary syndromes.

Acute Disease↗
PubMed2000

Effects of topically applied capsaicin cream on neurogenic inflammation and thermal sensitivity in rats.

The effects of capsaicin cream on neurogenic inflammation and thermal nociceptive threshold were investigated in rats. Firstly, for topical application of capsaicin cream to hind paw, we shaped boots from dental cement to prevent the animals from licking off the drug. Capsaicin cream (1%) led to significant increases in the amounts of Evans blue and substance P (SP) released into the perfusate, and the former response was significantly suppressed by pretreatment with RP67580, an NK1-receptor antagonist, but not by treatment with an NK2-receptor antagonist. Subsequent electrical stimulation of the sciatic nerve resulted in a significant reduction in Evans blue and SP extravasation 24 h after topical application of capsaicin cream. On the other hand, when capsaicin cream was repeatedly applied to both hind paws once a day, withdrawal latency for noxious heat stimulation decreased after 24 h, and this thermal hyperalgesia was reversed 3 days later. These results suggest that capsaicin cream initially affects neurogenic inflammation mechanisms and then blocks the pain transmission mechanism.

Administration, Topical↗
PubMed2000

Lack of association between T-786-->C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene and essential hypertension.

Accumulating evidence strongly suggests that an alteration in nitric oxide metabolism is involved in the pathogenesis of hypertension. We recently found 2 polymorphisms in the endothelial nitric oxide synthase (eNOS) gene, a Glu298Asp missense variant in exon 7 and a T-786-->C variant in the 5'-flanking region, which are not linked to each other. In our previous reports, we showed a positive association between the Glu298Asp variant and essential hypertension, myocardial infarction, and coronary spastic angina. We also revealed that the T-786-->C variant is strongly associated with coronary spastic angina and leads to the reduction of the eNOS gene promoter activity. To further investigate the genetic involvement of the eNOS gene in essential hypertension, we examined the frequency of T-786-->C variant in two independent populations of persons with essential hypertension in Kyoto (n=215) and Kumamoto (n=186) and compared the frequency with that in each age- and gender-matched control (233 controls in Kyoto and 223 controls in Kumamoto). In both groups, the frequency of T-786-->C variant was similar in patients with hypertension and normal controls. In conclusion, the T-786-->C variant was not positively associated with essential hypertension. Given the evidence of positive association of another polymorphism in the eNOS gene, the Glu298Asp polymorphism, with essential hypertension, special attention will be required to interpret the results of a case-control study for genetic risk factors.

Adult↗
PubMed2000

Association of human hepatocyte growth factor with hemodialysis hypotension.

Hypotension is a major cardiovascular complication of hemodialysis, and enhanced production of nitric oxide (NO) may be involved in hemodialysis hypotension. Human hepatocyte growth factor (hHGF), which induces endothelial proliferation, causes NO-mediated hypotension in animals. Because heparin, which is routinely used during hemodialysis, increases circulating hHGF concentration in humans, circulating hHGF may be involved in hemodialysis hypotension via increased NO production. To investigate the involvement of hHGF in NO production and hypotension in hemodialysis patients, we measured concentrations of serum hHGF and plasma NO3-, an index of endogenous NO production, in 114 patients undergoing maintenance hemodialysis. The mean serum hHGF concentration before dialysis was greater (p<0.01) in subjects with lower blood pressure (BP) (mean BP before dialysis < or =75 mmHg, n=16, 0.251+/-0.050 ng/ml) than in those with middle BP (mean BP before dialysis 76 to 109 mmHg, n=75, 0.143+/-0.016 ng/ml) or higher BP (mean BP before dialysis > or =110 mmHg, n=23, 0.088+/-0.017 ng/ml). The mean serum hHGF concentration after dialysis was higher in subjects with lower BP (1.854+/-0.242 ng/ml) than in those with middle BP (1.280+/-0.120 ng/ml) or higher BP (0.688+/-0.130 ng/ml). Serum hHGF concentration was positively correlated with plasma NO3- concentration (r=0.608, p=0.0001, n=114). Circulating hHGF may participate in the mechanism of chronic hemodialysis hypotension by affecting endogenous NO production.

Blood Pressure↗
PubMed2000

Induction therapy for non-small cell lung cancer with involved mediastinal nodes in multiple stations.

BACKGROUND: Metastasis to multiple stations of mediastinal nodes is associated with a poor prognosis. OBJECTIVE: : We prospectively examined the efficacy of induction therapy plus surgery in patients with non-small cell lung cancer and metastases at multiple stations of mediastinal (N2) lymph nodes. METHODS: Among the 1,085 patients who underwent surgery for primary non-small cell lung carcinoma from 1985 to 1997, those with clinical N2 disease of involved multiple stations, defined as bulky, mediastinal, lymph node metastases on CT scans, received induction therapy, consisting of cisplatin-based chemotherapy and radiation of 40 Gy. RESULTS: Of the 88 eligible patients entered into the study, 51 (58%) had multiple stations of N2 nodes affected preoperatively, as demonstrated by pathologic examination. Neither operative mortality nor fatal, treatment-related complications occurred during hospitalization. Patients who underwent complete resection had significantly longer survivals than did those who underwent incomplete resection (p = 0. 001). Among patients who underwent complete resection, the survival rate for patients with pathologically downstaged disease was significantly higher than that for patients whose disease was not downstaged (p = 0.009). Among patients with multiple stations of pN2 nodes involved who had undergone complete resection, those who received induction therapy for bulky N2 disease had a significantly better prognosis than did those undergoing surgery alone for nonbulky N2 disease (p = 0.03). CONCLUSIONS: Induction therapy prolonged the survival of patients with non-small cell lung cancer and mediastinal nodes involved at multiple stations. Survival was better when complete resection and downstaging of the disease were achieved after induction therapy.

Adult↗
PubMed2000

Lung cancer in women: sex-associated differences in survival of patients undergoing resection for lung cancer.

STUDY OBJECTIVES: The aim of this study was to analyze various characteristics and survival in female patients treated surgically for lung cancer. DESIGN: Retrospective clinical study. PATIENTS: From 1,242 consecutive cases of primary non-small cell lung cancer treated with pulmonary resection between June 1984 and December 1998, 337 female patients (27.1%) were chosen. RESULTS: Female patients had the following characteristics: a significantly younger age at onset (62.5 +/- 0.56 years vs 64.1 +/- 0.31 years for men), a higher frequency of adenocarcinoma (86.0% vs 48.3% for men), and smaller tumors (32.7 mm vs 38.3 mm in diameter for men). Peripheral tumors were significantly more common in women than men (71.8% vs 50.6%, respectively). Among 686 patients with a history of smoking, the women smoked significantly less often (12.8% vs 91.4% for men). Complete resection was achieved significantly less often in women (79.6% vs 85.2% for men); however, women having complete resection survived significantly longer than their male counterparts. Women with a postoperative negative carcinoembryonic antigen (CEA) had a significantly better prognosis than men; however, women with a postoperative positive CEA did not. Women > or = 60 years old survived significantly longer than their male counterparts, while women < 60 years old did not. CONCLUSIONS: Once the tumor was resected completely, women survived longer, partly due to the influence of life expectancy. However, the incidence of malignant effusion was higher and the rate of complete resection was lower in women.

Carcinoembryonic Antigen↗
PubMed2000

Decontamination of human xenotransplantable tumor with mouse hepatitis virus by implantation in nude rat: a case report.

A human tumor xenograft contaminated with mouse hepatitis virus (MHV) was implanted in a nude rat in order to decontaminate the tumor line. The decontamination failed in the first trial, but succeeded in the second trial. The difference between the two trials was the duration of implantation of the tumor in the nude rat, i.e., 12 days in the first and 24 days in the second trial. Duration of implantation might be a factor in the decontamination of transplantable tumors infected with MHV by passaging in the nude rat.

Animals↗
PubMed2000

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 16). Effects of short-term administration of carmofur on spermatogenesis.

Since morphological changes in the testes were observed in a 4 week repeated dose toxicity study of carmofur in rats, male Sprague-Dawley rats were administered the compound orally at 200 mg/kg by gavage for 11 days to assess the possibility of detecting abnormalities in spermatogenesis within a 2 week period. For comparison two studies were performed, treatment groups of fifteen and fourteen rats being given carmofur for 28 and 11 days, respectively. There were seven and nine rats that died or were killed in a moribund condition with 28 and 11 days treatment, respectively. Histopathologically, vacuolar degeneration of Sertoli cells, degeneration of elongated spermatids, exfoliation of round spermatids and multinucleated giant cell formation were observed in the testes of all animals and cell debris in ductus epididymidis was noted in almost all rats in the 28 days study. Exfoliation of round spermatids and multinucleated giant cell formation were detectable in two of five rats in the 11 days study, and vacuolar degeneration of Sertoli cells was also evident in four, though the changes were slight. No abnormalities were observed in the epididymides in the 11 days study. These results suggest that effects of carmofur on spermatogenesis can be detected with a treatment period of less than 2 weeks using histopathological examination of the testes. Therefore a 2-week repeated dose toxicity study has validity for detection of effects of carmofur on the male reproductive organs in the rats.

Administration, Oral↗
PubMed2000

Changes in vitreous concentrations of human hepatocyte growth factor (hHGF) in proliferative diabetic retinopathy: implications for intraocular hHGF production.

We measured human hepatocyte growth factor (hHGF) concentrations in the original vitreous and in the artificial vitreous after vitrectomy in 13 patients with proliferative diabetic retinopathy (PDR) undergoing repeated pars plana vitrectomy, in order to investigate whether the vitreous hHGF concentration is related to the recurrence of PDR after vitrectomy as well as to the original occurrence of PDR. We also examined the relationship between vitreous concentrations of hHGF and transforming growth factor-beta(2) (TGF-beta(2)), the predominant TGF-beta isoform in the vitreous, in 14 patients with PDR. For the original vitreous, mean hHGF concentrations were higher (P<0.05) in that from patients with severe PDR (vitreous haemorrhage, fibrovascular proliferation and tractional retinal detachment) than in that from patients with vitreous haemorrhage alone. In the artificial vitreous, mean vitreous hHGF concentrations were higher (P<0.05) in that from patients with severe PDR than in that from patients with vitreous haemorrhage alone or with vitreous haemorrhage plus fibrovascular proliferation. No correlation was found between the hHGF concentration in the artificial vitreous and time between vitrectomies. Vitreous hHGF concentrations were directly proportional to vitreous concentrations of latent TGF-beta(2) (r=0. 831; P=0.0002), but inversely proportional to vitreous concentrations of active TGF-beta(2) (r=0.495; P=0.072), which inhibits hHGF production. A decreased conversion of latent into active TGF-beta(2) in ocular disorders such as PDR is likely to result in an increased concentration of hHGF in the vitreous. Thus intraocular hHGF may be involved in pathological mechanisms causing not only the occurrence, but also the recurrence, of PDR.

Adult↗
PubMed2000

Rapid change of platelet aggregability in acute hyperglycemia. Detection by a novel laser-light scattering method.

We examined the alteration of platelet aggregability in acute hyperglycemia during 75-gram oral glucose tolerance tests (OGTT). Twenty subjects underwent 75-gram OGTT and venous blood samples were obtained before (0 min), 60, 120 and 180 min postload. Platelet aggregability shown as the number of small platelet aggregates was measured with a novel laser-light scattering (LS) method. Platelet aggregability increased in parallel with both glucose and immunoreactive insulin (IRI) levels. The number of mean small aggregates at 60 min (12.30 +/- 1.10 X 10(4)) was significantly higher than the one at 0 min (8.32 +/- 0.88 x 10(4), p <0.001), 120 min (10.63 +/- 0.98 x 10(4), p <0.05) and 180 min (8.28 +/- 0.84 x 104, p <0.001) (mean +/- SEM). Small aggregates correlated positively with plasma glucose levels at 60 min postload (r = 0.67, p = 0.001) while not with IRI. It might be important to suppress transient hyperglycemia for preventing the onset of acute coronary syndromes that could be closely related to platelet hyperaggregability.

Acute Disease↗
PubMed2000

[A case of intra-right atrial thrombus adhering to an intravenous hyperalimentation catheter].

We reported a clinical case of intra-right atrial giant thrombus adhering to an intravenous hyperalimentation(IVH) catheter. The patient was a 63 years-aged male, and was indwelled the IVH catheter for one month from right subclavian vein to right atrium to improve a malnutrition due to his advanced gastric cancer. Intra-cardiac mass was found in the right atrium by routine transthoracic echocardiography for the preoperative inspection; the giant mass(22 x 20 mm) had a low-echo density with a portion of high-echo density. In transesophageal echocardiography, the portion of high-echo density was found to be an IVH catheter and intra-right atrial mass was pierced by that catheter; however, it was difficult to determine whether the mass was either a vegetation or thrombus. The mass was removed by operation, and was diagnosed as a giant thrombus by histopathological examination. Thrombus should be taken into account as a possible cause of intra-right atrial mass when an IVH catheter was indwelled in the right atrium.

Catheters, Indwelling↗
PubMed2000

[Interference by D-mannitol on serum D-arabinitol determination by enzymatic assay].

We examined a disparity in D-arabinitol values between two commercial assay kits, LABOFIT and ARABINITEC-AUTO. The determined values by the former were increased by 26%(y = 0.2643x) because of concomitant D-mannitol, whereas those by our newly developed ARABINITEC-AUTO was increased only by 2%(y = 0.0242x). Of 109 samples, 5 samples were found to contain more than 100 mumol/l of D-mannitol. A clear relation(r = 0.89) was noted between the degree of disparity between measurements by the two methods and D-mannitol concentrations in samples. Thus, we have proved that the disparity is mainly caused by D-mannitol.

Biomarkers↗
PubMed2000

Genetic risk factors for coronary artery spasm: significance of endothelial nitric oxide synthase gene T-786-->C and missense Glu298Asp variants.

BACKGROUND: We recently identified two endothelial nitric oxide synthase (eNOS) gene polymorphisms, Glu298Asp and T-786-->C, which are independently associated with coronary spasm. eNOS gene intron 4b/a polymorphism is also reported to be involved in smoking-dependent coronary artery disease. The genetic linkage among these polymorphisms remains unknown. Also, it is unclear which variant is most responsible for coronary spasm. In the present study, we first examined the genetic linkage among these three variants. Next, we studied the risk factors of coronary spasm by using all significant genetic and conventional risk factors in a large-scale study. METHODS: The genotype and allele frequencies for the T-786-->C, intron 4b/a, and Glu298Asp variants were assessed in 423 randomly selected DNA samples to examine their genetic linkages. The relative capacities of all risk factors to predict coronary spasm were then analyzed using multiple logistic regression in 201 patients with coronary spasm and 345 volunteers. RESULTS: Comparison of allele frequencies revealed that the eNOS intron 4a allele was significantly linked to the T-786-->C mutation (P < 0.00001), whereas there was not a linkage between the intron 4a allele and the Glu298Asp variant (P = 0.1437) or between the Glu298Asp variant and the T-786-->C mutation (P = 0.1996). Multiple logistic regression revealed that the most predictive independent risk factor for coronary spasm was the T-786-->C mutation (P < 0.001), followed by cigarette smoking (P < 0.001), hypertension (P = 0.004), and the Glu298Asp variant (P = 0.028). CONCLUSIONS: We found that the T-786-->C mutation and the intron 4a allele are in linkage disequilibrium. We previously showed that the T-786-->C mutation reduced eNOS gene promoter activity. In that context, our results strongly suggest that the T-786-->C mutation underlies the functional characteristics of the intron 4a allele. Further, multiple logistic regression analysis revealed that the T-786-->C mutation is the most predictive risk factor for coronary spasm, followed by cigarette smoking. Given that those effects are potentially additive, patients carrying the eNOS gene variants should be strongly cautioned against smoking.

Adult↗
PubMed2000

[Spinal cord infarction presenting Brown-Séquard syndrome with impaired position sense].

A 79-year-old hypertensive man presented left hemiplegia of sudden onset. Neurological examination revealed weakness of the left extremities, with hypoalgesia on the opposite side below the level C 4. He also showed Horner syndrome, facial hypoalgesia, weakness of sternocleidmastoid and trapezius muscles on the paralyzed side. The position and vibration senses were impaired on the left extremities. The position sense was more disturbed on his upper limb, to the extent that the patient was not able to recognize where his wrist was located. The cervical MRI exhibited a high signal intensity on the left half of the cord between C 2-C 5 vertebral level on T 2 WI. Bilateral vertebral arteries were patent, though severe stenosis of internal-external carotid artery bifurcation was observed on MRA. Asymmetrical distribution of upper cervical cord arteries, severe atherosclerotic change of cervical and intracranial vessels, and spondylotic cervical canal stenosis were suggested to contribute to cause the lateralized infarction of the cord, involving not only the anterior, but also posterior part, where Burdach's fascicle were probably more affected.

Aged↗
PubMed2000

[Central necrosis of the lumbo-sacral segment of the spinal cord associated with multiple cholesterin emboli, clinically presenting as acute paraplegia].

A seventy-six-year-old man suddenly suffered from paraplegia and pain in both legs. He had been maintained on hemodialysis and committed a suicide attempt by cutting the shunt at the paraplegic attack. He was brought to the emergency ward for the treatment of hemorrhagic preshock. Neurological examination demonstrated flaccid paraplegia, loss of tendon reflex in the lower extremities, dissociated sensory loss below the fourth lumbar level; and incontinence in defecation. MRI showed T2 shortening in the ventral spinal cord caudal below the level of the eleventh thoracic cord. Postmortem examination confirmed ischemic infarct in the central area of the spinal cord, associated with disseminated cholesterin emboli in the small arteries. This case was the first MRI demonstration of central necrosis caused by cholesterin emboli, and may emphasize the significance of cholesterin emboli in the spinal arterial disorders in the aged.

Acute Disease↗
PubMed1999

Responsiveness of rat substantia gelatinosa neurones to mechanical but not thermal stimuli revealed by in vivo patch-clamp recording.

1. Synaptic responses of 46 substantia gelatinosa (SG) neurones in the spinal dorsal horn to cutaneous mechanical and/or thermal stimuli were investigated in an in vivo rat preparation with whole-cell patch-clamp recordings. The clamped neurones were identified as being in the SG based on either their morphological features by intrasomatic injection of biocytin or the depth of the neurones from the surface of the spinal cord. 2. In all SG neurones examined where spontaneous EPSCs occurred, pinch (noxious) and air (innocuous) stimuli applied to the ipsilateral hindlimb elicited a barrage of EPSCs (some of which initiated an action potential under current-clamp conditions), which subsided just after cessation of the stimuli without any residual slow current (or after-discharge). The spontaneous and evoked EPSCs were reversibly abolished by a non-N-methyl-D-aspartate (non-NMDA) receptor antagonist, CNQX (20 microM). 3. Noxious (>= 45 C) or innocuous (<= 40 C) thermal stimuli did not elicit any synaptic responses in all 18 SG neurones tested which were sensitive to mechanical stimuli. Noxious cold stimulation (<= 10 C) also failed to produce any responses (n = 6). 4. It is concluded that both noxious and innocuous mechanical information to SG neurones are transmitted primarily by activation of non-NMDA receptors, probably without any involvement of slow synaptic transmission, and that thermal information is conveyed to areas of the dorsal horn other than SG.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1999

The methylation status of cytosines in a tau gene promoter region alters with age to downregulate transcriptional activity in human cerebral cortex.

Changes with age in the methylation status of cytosines in a promoter region of the tau gene were investigated in autopsy human cerebral cortex, using the bisulfite method, polymerase chain reaction (PCR) and direct sequencing of PCR products. While the total number of methylcytosines decreased with age, the changes in methylation status differed among transcription factor binding sites. Cytosines in the AP2-binding sites were never methylated in any of the cases studied at any age. Methylcytosines in the binding sites for Sp1, a transcriptional activator, significantly increased with age, whereas those in the binding sites for GCF, a repressor of GC-rich promoters, significantly decreased with age. These findings suggest that the methylation status of cytosines in the promoter region of the tau gene alters with age to decrease its transcriptional activity in the human cerebral cortex.

Adult↗