Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 145 records · Page 8Linked to original sources

PubMed1999

Reorganization of the primary afferent termination in the rat spinal dorsal horn during post-natal development.

To study the reorganization of the primary afferent input in the spinal dorsal horn during post-natal development, synaptic responses evoked by large Abeta and fine Adelta afferents were recorded from substantia gelatinosa (SG) neurons in slices obtained from immature (post-natal days 21-23) and mature rats (post-natal days 56-60). Threshold stimulus intensities and conduction velocities (CVs) of Abeta and Adelta afferents were determined by intracellular recordings of the antidromic action potentials from dorsal root ganglion (DRG) neurons isolated from immature and mature rats. In immature rats, excitatory postsynaptic currents (EPSCs) were elicited by stimulation sufficient to activate Abeta afferents in the majority of SG neurons (64.9%, 24 of 37 neurons), while most EPSCs observed in mature rats were elicited by stimulation of Adelta afferents (62.5%, 25 of 40 neurons). These observations suggest that the primary afferents innervating SG neurons were reorganized following maturation; Abeta afferents were the predominant inputs to the SG neurons in the immature state, thereafter Adelta afferents were substituted for the Abeta afferents to convey sensory information to the SG neurons. This relatively slow reorganization of the sensory circuitry may correlate with slow maturation of the SG neurons and with a delay in the functional connections of C afferents to the SG neurons.

Animals↗

PubMed1999

Decrease with age in methylcytosines in the promoter region of receptor for advanced glycated end products (RAGE) gene in autopsy human cortex.

Changes with age in the methylation status of cytosines in the promoter region of the receptor for advanced glycated end products (RAGE) in autopsy human cortex were investigated, using the bisulfite method, polymerase chain reaction (PCR), and direct sequencing of PCR products. The total number of methylcytosines significantly decreased with age. While the number of methylated cytosines at CpG dinucleotides was stable throughout adult life, that at sites other than CpG dinucleotides significantly decreased with age in cases >/=70 years old. Of 13 transcription factor binding sites, cytosines in CpG doublets in NF-IL6 and SP-1 binding sites were methylated in all cases, suggesting that these sites are repressed throughout adulthood. In contrast, the number of methylcytosines in AP-2 or SP-1 binding sites located at CpC, CpA, or CTG was significantly lower or at least tended to be lower in cases >/=70 years than <70 years old. These reductions in the number of methylcytosines at transcription factor binding sites may increase expression of RAGE, which may in turn play a role in aging of the brain.

5-Methylcytosine↗

PubMed1999

Plasma soluble intercellular adhesion molecule-1 levels in coronary circulation in patients with unstable angina.

It has been suggested that active inflammation plays an important role in the pathogenesis of acute coronary syndromes, including unstable angina. Intracellular adhesion molecule-1 (ICAM-1) is a major ligand on the endothelial cells for adherence of the activated polymorphonuclear leukocytes. Recently, it has been demonstrated that the soluble form of ICAM-1 has been detected in human serum and has been increased in many other inflammatory or autoimmune disorders. To evaluate the involvement of ICAM-1 in unstable angina, we examined plasma soluble ICAM-1 (sICAM-1) levels in coronary circulation. The plasma sICAM-1 levels in the coronary sinus and aortic root were simultaneously examined in 20 patients with unstable angina, 19 patients with stable exertional angina, and 16 control subjects. The plasma levels of sICAM-1 were measured by enzyme-linked immunosorbent assay. The mean plasma sICAM-1 levels (nanograms per milliliter) both in the coronary sinus and aortic root were significantly higher (p <0.01) in patients with unstable angina than in those with stable exertional angina and in control subjects (217+/-14 vs 126+/-8; 120+/-10 in the coronary sinus, 202+/-13 vs 125+/-9; 123+/-10 in the aortic root). Furthermore, the mean value was higher in the coronary sinus than in the aortic root in patients with unstable angina. There were no significant differences in the values between in the coronary sinus and aortic root in patients with stable exertional angina and control subjects. Thus, sICAM-1 release is increased, especially in coronary circulation in unstable angina.

Aged↗

PubMed1999

Effect of interleukin-1 beta on cardiac hypertrophy and production of natriuretic peptides in rat cardiocyte culture.

This study was designed to examine the effects of interleukin-1 beta (IL-1 beta) on myocyte (MC) hypertrophy and the production of A-type natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in rat ventricular cardiocyte culture, and to investigate the role of nonmyocyte (NMC) in this process. We examined the effects of IL-1 beta on the production of ANP and BNP in comparison with the effects of endothelin-1 (ET-1) by using two types of neonatal rat cardiocyte culture; MC-enriched culture and MC-NMC coculture. In the MC-enriched culture, the increase in secretion of ANP and BNP was small in treatment with IL-1 beta (1000 pg/ml), while ET-1 (10 nM) markedly augmented the secretion of ANP and BNP. In the MC-NMC coculture, IL-1 beta and ET-1 each significantly augmented the secretion of ANP and BNP. The degree of the increase of ANP and BNP was equivalent between IL-1 beta and ET-1. As for the morphological changes of MCs, IL-1 beta induced the star-shaped MC hypertrophy characterized by elongation and pointed edges only in the MC-NMC coculture, while ET-1 induced the MC hypertrophy characterized by shapes of squares, triangles or circles in both cultures. This study shows that IL-1 beta induces unique cardiac hypertrophy and the marked secretion of ANP and BNP, and that NMC is indispensable when treated with IL-1 beta.

Animals↗

PubMed1999

Local variation in expression of pro- and antithrombotic factors in vascular endothelium of human autopsy brain.

The expression of tissue factor (TF), tissue factor pathway inhibitor (TFPI), von Willebrand factor (vWF), endothelial nitric oxide (NO) synthase (eNOS), tissue plasminogen activator (tPA), its inhibitor (PAI-1), and myosin, an indicator of local shear stress, was examined in the endothelium of cerebral vessels according to vessel size and location in human autopsy brains, using immunohistochemistry. Expression of TF, vWF, eNOS, tPA/PAI-1, and myosin was much greater in intracerebral perforating arteries and the microvasculature than the pial and carotid arteries. Expression of all antigens studied was normally faint or negative in the pial and carotid arteries. However, TF, vWF, myosin, tPA, and PAI-1 were strongly expressed in the endothelium of the inner wall of the carotid bifurcation where flowing blood collides, but not in the outer wall. In the endothelium of arteries with fibrillary hyperplasia, vWF, myosin, eNOS, tPA, and PAI-1 were strongly expressed. Within the brain, microvascular expression of TFPI was very faint or negative, whereas that of vWF was intense throughout all brain regions. However, expression of TF and myosin was more intense in the basal gray matter and white matter than in the cortex. eNOS was expressed more strongly in the basal gray matter and cortex than the white matter, whereas tPA and PAI-1 expression was more intense in the white matter than the gray matter. In addition to intrinsic properties of individual vessels, these local variations in expression of pro- and antithrombotic factors in cerebral vessels may in part be due to differences in hemorheological and humoral environments to which they are exposed, and may result in local difference in vulnerability to ischemia. The present findings may in part account for the propensity of thrombus generation in the carotid inner wall, an usual source of artery-to-artery microemboli, frequent development of lacunar (small) infarcts in deep brain regions, and diffuse white matter lesions as seen in Binswanger's leukoencephalopathy.

Adult↗

PubMed1999

A minireview of studies conducted in japan using finger-skin temperature during cold-stress tests for the diagnosis of hand-arm vibration syndrome.

For the diagnosis of the hand-arm vibration syndrome, cold-stress tests using different water temperatures and periods of hand immersion have been investigated in Europe, North America, and Japan. In recent years, peripheral circulation and sensory tests, including finger-skin temperature measurement involving immersion of one hand in cold water at 10 degrees C for 10 min, have been widely accepted in Japan. On the other hand, standardization of the vascular assessment method is under discussion at the International Organization of Standardization. We reviewed research findings from Japan concerning finger-skin temperature measurement during the cold-stress test, especially factors influencing the test results and the diagnostic significance. For establishment of the cold-stress test for epidemiology studies of the hand-arm vibration syndrome, standardization of the environmental factors influencing the test results and reporting of its sensitivity and specificity are needed.

Arm↗

PubMed1999

Presence of sodium dodecyl sulfate-stable amyloid beta-protein dimers in the hippocampus CA1 not exhibiting neurofibrillary tangle formation.

The amyloid cascade hypothesis of Alzheimer's disease postulates that accumulation of amyloid beta-protein (Abeta) precedes neurofibrillary tangle formation or neuronal loss in the cortex. Although this temporal profile has been proved in the neocortex by silver staining and immunocytochemical methods, CA1 of the hippocampus exhibits a distinct temporal profile during normal aging: the formation of neurofibrillary tangles precedes senile plaque formation. This temporal profile has been further confirmed by two-site enzyme immunoassay (EIA) quantitation of sodium dodecyl sulfate (SDS)-dissociable Abeta42; neurofibrillary tangles are already present despite undetectable levels of SDS-dissociable Abeta42. However, when the same specimens were subjected to Western blotting, many cases with or without neurofibrillary tangles showed some accumulation of SDS-stable Abeta dimers that cannot be detected by EIA. Thus, the temporal profile prerequisite for the hypothesis is still valid in CA1, and this finding also suggests that SDS-stable Abeta dimers have some significant effects on CA1 pyramidal neurons, which are most vulnerable to neurofibrillary tangle formation.

Adult↗

PubMed1999

Appearance of sodium dodecyl sulfate-stable amyloid beta-protein (Abeta) dimer in the cortex during aging.

We previously noted that some aged human cortical specimens containing very low or negligible levels of amyloid beta-protein (As) by enzyme immunoassay (EIA) provided prominent signals at 6 approximately 8 kd on the Western blot, probably representing sodium dodecyl sulfate (SDS)-stable Abeta dimer. Re-examination of the specificity of the EIA revealed that BAN50- and BNT77-based EIA, most commonly used for the quantitation of Abeta, capture SDS-dissociable Abeta but not SDS-stable Abeta dimer. Thus, all cortical specimens in which the levels of Abeta were below the detection limits of EIA were subjected to Western blot analysis. A fraction of such specimens contained SDS-stable dimer at 6 approximately 8 kd, but not SDS-dissociable A(beta) monomer at approximately 4 kd, as judged from the blot. This A(beta) dimer is unlikely to be generated after death, because (i) specimens with very short postmortem delay contained the A(beta) dimer, and (ii) until 12 hours postmortem, such SDS-stable A(beta) dimer is detected only faintly in PDAPP transgenic mice. The presence of A(beta) dimer in the cortex may characterize the accumulation of A(beta) in the human brain, which takes much longer than that in PDAPP transgenic mice.

Adult↗

PubMed1999

Evaluation of TMN classification for lung carcinoma with ipsilateral intrapulmonary metastasis.

BACKGROUND: Staging for lung cancer based on the TNM classification is an important predictive factor for prognosis. Recently, lung cancer with ipsilateral intrapulmonary metastasis (PM) was reclassified according to the revision of the TNM classification. To evaluate the prognostic importance of the new staging system for PM, we analyzed the postoperative survival of patients with non-small cell lung carcinoma. METHODS: Of 1,002 consecutive patients who underwent operation for primary lung cancer between June 1984 and December 1996, we reviewed the medical record of 889 patients who underwent complete resection for non-small cell lung cancer. RESULTS: We considered 89 patients (10.0%) to have synchronous ipsilateral PM. After reclassification to the former staging system revised in 1992, 5 patients were classified as stage I, 29 as stage IIIA, 48 as stage IIIB, and 7 as stage IV. In the new staging system revised in 1997, 48 patients were recategorized as stage IIIB, and 41 as stage IV. The 5-year survival of patients without PM (49.5%) was significantly better than that of patients with PM in primary-tumor lobe (29.6%, p = 0.002) or in nonprimary-tumor ipsilateral lobe (23.4%, p = 0.0002). Although the survival of patients with stage IV cancer without PM was significantly worse than that of patients with the new (1997) stage IV cancer with PM (p = 0.02), it was similar to that of patients with the former (1992) stage IV cancer with PM. The survival of PM patients with N0 or N1 disease was significantly better than that of PM patients with N2 or N3 disease (p = 0.001). Furthermore, in patients with the new (1997) stage IIIB cancer, the survival of N0 disease was better than that of N2 disease (p = 0.007). CONCLUSIONS: Inasmuch as the prognosis of non-small cell carcinoma in patients with PM strongly correlated with N factor rather than PM factor, N factor should be reflected in a staging designation. We therefore consider the new TNM classification for PM reclassified in 1997 to be less acceptable for surgical-pathologic staging than the revision in 1992.

Adult↗

PubMed1999

How should interlobar pleural invasion be classified? Prognosis of resected T3 non-small cell lung cancer.

BACKGROUND: The results of surgical treatment for non-small cell lung cancer with interlobar pleural involvement and direct invasion of the other lobe have seldom been documented. METHODS: Of 1,130 consecutive patients who were operated on for primary bronchogenic carcinoma between 1984 and 1997, we studied 132 patients who had complete resection of T3 non-small cell carcinoma. RESULTS: The structures involved were as follows: parietal pleura, 49 patients; chest wall, 45; interlobar pleura, 19; main bronchus within 2 cm of the carina, 11; mediastinal pleura, 6; and diaphragm, 1. Patients with N2 disease had a significantly worse survival than those with N0 (p = 0.0054) and N1 disease (p = 0.0165). The survival of patients with involvement of the interlobar pleura was significantly worse than that of patients with T1 (p = 0.0001) or T2 disease (p = 0.0484), and was similar to that of patients with T3 disease (p = 0.9821). CONCLUSIONS: In patients with T3 disease, mediastinal lymph node involvement influenced survival significantly. Patients with involvement of the interlobar pleura should be regarded as having T3 lesions.

Adult↗

PubMed1999

Extended sleeve lobectomy for lung cancer: the avoidance of pneumonectomy.

OBJECTIVE: We have tried atypical bronchoplasties in patients with noncompromised lung function with centrally located cancers to avoid pneumonectomy. We evaluated the efficacy of extended sleeve lobectomy in such patients. METHODS: Among 157 patients undergoing bronchoplasty for primary non-small cell lung carcinoma, 15 patients underwent extended sleeve lobectomy. RESULTS: According to the mode of reconstruction, the 15 patients were classified into 3 groups: (A) anastomosis between the right main and lower bronchi with resection of the upper and middle lobes (n = 6), (B) anastomosis between the left main and basal segmental bronchi with resection of the upper lobe and superior segment of the lower lobe (n = 4), and (C) anastomosis between the left main and upper division bronchi with resection of the lingular segment and lower lobe (n = 5). The tumors were completely resected in all patients. Pulmonary angioplasty was carried out in 8 patients. Bronchial reconstruction was successful in all patients. Pulmonary vein thrombosis resulting from overstretching of the inferior pulmonary vein occurred in 1 patient of group A and was relieved by completion pneumonectomy. There was neither operative mortality nor local recurrence. Although all patients with stage IIB disease and half of patients with stage IIIA disease were alive without recurrence (12-106 months), half of the patients with stage IIIA disease died of distant metastases within 1 year. CONCLUSIONS: We suggest that this extended sleeve lobectomy, which is technically demanding, should be considered in patients with centrally located lung cancer, because this lung-saving operation is safer than pneumonectomy and is equally curative.

Aged↗

PubMed1999

Prognosis of completely resected pN2 non-small cell lung carcinomas: What is the significant node that affects survival?

OBJECTIVE: We analyzed the effect of the station of mediastinal metastasis with regard to the location of the primary tumor on the prognosis in patients with non-small cell lung cancer. METHODS: Of 956 consecutive patients who underwent operation for primary lung carcinoma between 1986 and 1996, 760 patients (79.5%) were diagnosed as having non- small cell carcinoma and were subjected to complete removal of hilar and mediastinal lymph nodes together with the primary tumor. RESULTS: The status of lymph node involvement was N0 in 480 patients (63.2%), N1 in 139 patients (18.3%), and N2 in 141 patients (18.6%). The 5- and 10-year survival of patients with N2 disease were 26% and 17%, respectively. Neither cell type nor the extent of procedure was a significant survival determinant. Patients having involvement of subcarinal nodes from upper-lobe tumors had a significantly worse prognosis than those patients with metastases only to the upper mediastinal or aortic nodes (P =.003). Patients with nodal involvement of the upper mediastinum from lower-lobe tumors had a significantly worse survival than those patients with metastases limited to the lower mediastinum (P =.039). Furthermore, patients with involvement of the aortic nodes alone from left upper-lobe tumors had a significantly better survival than those patients with metastasis to the upper or lower mediastinum beyond the aortic region (P =.044). CONCLUSIONS: When mediastinal metastasis is limited to upper nodes from upper-lobe tumor, to lower nodes from lower-lobe tumor, or to aortic nodes from left upper-lobe tumor, acceptable survival could be expected after radical resection.

Adult↗

PubMed1999

Examination of signal transduction pathway of stimulated B1 and B2 kinin receptors; MAP kinase pathway to AP-1 translocation in HEK 293 cells.

B1 or B2 kinin receptor-overexpressing HEK293 cells were stimulated with des-Arg9-BK or BK, respectively. Each agonist induced translocation of AP-1 into the nuclear fraction as well as activation of MAP kinases in each cells. MAP kinase inhibitor PD98059 suppressed translocation of AP-1 and agonist-induced MAP kinase activation in both cells. These results indicate that stimulation of B1 or B2 receptor expresses a feature of the signal transduction pathway of MAP kinase activation to translocation of AP-1. This signal transduction pathway of HEK cells through B1 and B2 receptors may be similar in response to respective agonists.

Animals↗

PubMed1999

Bicuculline-resistant, Cl- dependent GABA response in the rat spinal dorsal horn.

Receptors for gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the mammalian central nervous system (CNS), have been divided into three subtypes. GABA(A) receptor is a ligand-gated chloride channel that is competitively antagonized by bicuculline, whereas GABA(B) receptor regulate Ca2+ or K+ channels through G proteins. Recently, GABA(C) receptor has been identified in mammalian and fish retina. Unlike GABA(A) receptors, the GABA(C) receptor is a bicuculline-resistant chloride channel that is selectively activated by cis-4-aminocrotonic acid (CACA), and antagonized by imidazole-4-acetic acid (I4AA) and to some extent by picrotoxin. We report here that bicuculline-resistant GABA responses mediated by chloride channels are also expressed in substantia gelatinosa (SG) neurons in the dorsal horn, which receive predominantly nociceptive inputs from periphery. The GABA responses are, however, not mimicked by CACA nor affected by I4AA, but abolished by picrotoxin. Moreover, these responses are modulated by benzodiazepines (flunitrazepam) and barbiturates (thiopental), although GABA(C) responses are not affected. Thus, the pharmacological characteristics of the GABA responses observed in SG neurons are distinct from those responses mediated by the known GABA receptors. These differences may reflect the presence of receptor subunits unique to SG neurons.

Animals↗

PubMed1999

Angiotensin-converting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction.

OBJECTIVES: We investigated the effects of enalapril therapy on plasma tissue factor (TF), tissue factor pathway inhibitor (TFPI) and monocyte chemoattractant protein-1 (MCP-1) levels in patients with acute myocardial infarction. BACKGROUND: Macrophages express TF in human coronary atherosclerotic plaques. Both TF and TFPI are major regulators of coagulation and thrombosis. Monocyte chemoattractant protein-1 is a monocyte and macrophage chemotactic and activating factor. METHODS: In a randomized, double-blind, placebo-controlled study beginning about two weeks after myocardial infarction, 16 patients received four weeks of placebo (placebo group) and another 16 patients received four weeks of enalapril 5 mg daily therapy (enalapril group). We performed blood sampling after administration of the doses. RESULTS: There were no significant differences in the serum angiotensin-converting enzyme (ACE) activity, plasma TF, free TFPI or MCP-1 levels before administration between the enalapril and placebo groups. In the enalapril group, ACE activity (IU/liter) (14.0 before, 5.2 on day 3, 5.8 on day 7, 6.3 on day 28), TF levels (pg/ml) (223, 203, 182, 178) and MCP-1 levels (pg/ml) (919, 789, 790, 803) significantly decreased by day 28. However, the free TFPI levels (ng/ml) (28.2, 26.5, 26.8, 28.4) did not change. These four variables were unchanged during the study period in the placebo group. CONCLUSIONS: This study demonstrated that administration of enalapril reduces the increased procoagulant activity in patients with myocardial infarction associated with inhibition of the activation and accumulation of macrophages and monocytes.

Aged↗

PubMed1999

Quantitation of nicotinic acetylcholine receptor subunits alpha 4 and beta 2 messenger RNA in postmortem human brain using a non-radioactive RT-PCR and CCD imaging system.

We present a simple and rapid procedure for quantifying mRNA in the brain after RT-PCR, in which the intensity of the ethidium bromide luminescence of PCR products is measured directly from electrophoretic gels by a highly sensitive CCD camera combined with an image analyzing computer system (Gel Doc 1000 system). The CCD camera allows the mRNA in the ethidium bromide-stained PCR-amplified bands to be quantified in a broad exponential range of PCR cycles. The proposed protocol enables standard curves to be constructed to examine the relationship between the number of reaction cycles and amplified log intensity and between the amount of sample RNA for RT-PCR and amplified intensity. The method was applied to nicotinic acetylcholine receptor (nAChR) subunits alpha 4 and beta 2 mRNA in postmortem human putamen in the present study, but is also applicable to mRNAs of other receptors and neurotransmitter precursor peptides.

Actins↗

PubMed1999

Serum hepatocyte growth factor levels in Henoch-Schönlein purpura.

BACKGROUND: Henoch-Schönlein purpura (HSP) is the most common form of vasculitis in children. The potential role of hepatocyte growth factor (HGF) in acute immune-mediated vasculitis has not been elucidated. METHODS: Serum HGF levels were determined in patients with HSP. RESULTS: In patients with acute-phase HSP, mean (+/- SD) serum HGF levels were 0.32 +/- 0.14 ng/mL and were significantly higher than those in the control group (0.11 +/- 0.10 ng/mL). This elevation of serum HGF levels recovered to control levels in parallel with improvement of the clinical symptoms. CONCLUSIONS: It is suggested that elevation of serum HGF levels in patients with acute-phase HSP may reflect endothelial cell damage or dysfunction in HSP.

Acute Disease↗

PubMed1999

Free peroneal skin flap for oropharyngeal reconstruction.

The thicknesses of three dermal flaps, platysma, forearm, and fibula, which are often used for oropharyngeal reconstruction, were measured in 21 subjects using 15 MHz Doppler ultrasonography. The mean (SD) thicknesses were 2.2 (0.3), 3.1 (0.5), and 3.8 (0.6) mm, respectively. The free peroneal skin flap from the leg was used in 14 patients with head and neck cancer. These flaps were successfully transplanted in 13 of 14 patients (93%) with no problems at the donor site. This flap offers many advantages, including its distance from the head and neck, its cosmetic superiority to a forearm flap, it allows two flaps with two cutaneous branches, it is possible to close the donor site primarily without a skin graft, and it has thin subcutaneous tissue. We found that the free peroneal skin flap is particularly useful for oropharyngeal reconstruction.

Adult↗