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Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 235 records · Page 13Linked to original sources

Simultaneous elevation of the levels of circulating monocyte chemoattractant protein-1 and tissue factor in acute coronary syndromes.

The levels of circulating monocyte chemoattractant protein-1 (MCP-1) and tissue factor (TF) were examined on admission in 46 consecutive patients with acute coronary syndromes (ACS) and 30 patients with stable exertional angina (SEA). The plasma levels of both MCP-1 and TF were higher in the ACS patients than in the SEA patients (MCP-1: p<0.001; TF: p<0.001). Only the circulating TF level related to the number of diseased vessels. A positive correlation between plasma MCP-1 and TF levels was found (r=0.476, p<0.001). These results suggest that circulating MCP-1 plays an important role in the pathogenesis and/or development of ACS.

Acute Disease↗

Occult papillary thyroid carcinoma in Hashimoto's thyroiditis presenting as a metastatic bone tumor.

Some occult thyroid carcinomas are hypothesized to regress and be eventually obliterated. We report here a patient whose condition supports this hypothesis. A 51-year-old male with primary hypothyroidism due to Hashimoto's thyroiditis suffered from a rib bone tumor. He had a diffuse goiter with no nodular lesion. Serum FT4 and TSH concentrations were 0.8 ng/dl and 36.4 microU/ml on taking 100 microg/day of T4. Anti-Tg- and -TPO-Ab were strongly positive (99 and 1380 U/ml). The iodine 123 scintigraphy demonstrated clear accumulation in the rib tumor, whereas the thyroid was scarcely visible. Biopsy of the rib tumor showed papillary proliferation of large atypical cells, which were immunohistochemically positive for thyroglobulin. Metastatic bone tumor of papillary thyroid carcinoma was therefore strongly suspected. He underwent a total thyroidectomy and the thyroid was stepwise sectioned completely at 3 mm intervals. The thyroid condition was diagnosed as Hashimoto's thyroiditis demonstrating diffuse and dense fibrosis, lymphocyte infiltration with lymphoid follicles and flattened atrophied follicles, but no carcinomatous foci were found. He was treated with I-131 and scintigraphy after the ingestion showed distinct accumulation in the rib tumors similar to that before thyroidectomy. No other abnormal uptake was observed. It is suggested that the primary occult thyroid papillary carcinoma regressed and was obliterated possibly by some immunologic or other host-resistance factors after it metastasized to the distant bone.

Bone Neoplasms↗

Rapid diagnosis of oral tuberculosis by amplification of Mycobacterium DNA from paraffin embedded specimens.

The polymerase chain reaction (PCR) assay is a powerful tool for quick diagnosis of various infectious diseases. We applied this technique as well as conventional histopathological examination to diagnose oral tuberculosis. Ziehl-Neelsen staining of oral mucosal specimens often fails to detect Mycobacterium (M.) tuberculosis due to the low number of bacteria in the tissue. Specific primers and probes were synthesized based upon the nucleotide sequence of the 65 kDa membrane protein of M. tuberculosis. DNA extracted from the paraffin-embedded tissue was amplified using taq polymerase. PCR assay detected M. tuberculosis in 5 of 6 samples. Although the gene segments from these species were quite similar, the gamma 32P labeled noligonucleotide probes distinguished between M. tuberculosis and M. fotuitum by southern blot hybridization. In all specimens that were Ziehl-Neelsen negative, M. tuberculosis DNA was detected by PCR. These results suggest that PCR is a useful means of diagnosing mycobacterium infection.

Adult↗

Multidrug resistance mediated by overexpression of P-glycoprotein in human osteosarcoma in vivo.

We examined the expression levels of P-glycoprotein (P-Gp)/the human multidrug resistance gene (MDR1) and in vivo chemosensitivity in the 7 osteosarcoma xenografts. Three of seven (43%) osteosarcoma xenografts expressed MDR1 by reverse transcriptase-polymerase chain reaction (RT-PCR). The OSS-516R xenograft selected with vincristine (VCR) from the MDR1-negative xenograft OSS-516, which was sensitive to VCR and doxorubicin (DOX), acquired cross-resistance to DOX. In the OSS-516R, RT-PCR assay showed definite MDR1 expression and immunohistochemical analysis demonstrated P-Gp-positive tumor cells. These results suggest that P-Gp/MDR1 overexpression is related to multidrug resistance in human osteosarcoma in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Change in intraocular pressure after intraocular lens implant during a follow-up period of over 10 years].

Changes in intraocular pressure were studied in 141 eyes following intraocular lens implant. The average observational time was twelve years. We tried to fix both loops of the implant in the ciliary sulcus. The intraocular pressure increased over the ten year interval at 0.19 mmHg per year. Twenty-seven of the 141 eyes developed glaucoma. We studied the intraocular pressure of the cases with or without complications. Thirty-eight eyes had complications, fifteen eyes (39%) developed secondary glaucoma, and three eyes (8%) developed glaucomatous visual field defect. In twenty-three cases without secondary glaucoma, the intraocular pressure increased over a three-year interval after surgery and remained constant thereafter. 103 eyes had no complications to influence the intraocular pressure, twelve eyes (12%) developed secondary glaucoma, and four eyes (4%) developed glaucomatous visual field defect. In 91 cases without secondary glaucoma, the intraocular pressure increased over a five-year interval after surgery at 0.28 mmHg per year and remained constant thereafter. We recommend regular examination, especially during the initial five-year period when the intraocular pressure is apt to increase even if complications are not evident.

Adult↗

Astrocytes containing amyloid beta-protein (Abeta)-positive granules are associated with Abeta40-positive diffuse plaques in the aged human brain.

Amyloid beta-protein (Abeta) is the major component of senile plaques that emerge in the cortex during aging and appear most abundantly in Alzheimer's disease. In the course of our immunocytochemical study on a large number of autopsy cases, we noticed, in many aged nondemented cases, the presence of unique diffuse plaques in the cortex distinct from ordinary diffuse plaques by immunocytochemistry. The former were amorphous, very faintly Abeta-immunoreactive plaques resembling diffuse plaques, but they stained for Abeta40 and were associated with small cells containing Abeta-positive granules. A panel of amino- and carboxyl-terminal-specific Abeta antibodies showed that such Abeta40-positive diffuse plaques and cell-associated granules were composed exclusively of amino-terminally deleted Abeta terminating at Abeta40, -42, and -43. Double immunostaining also showed that those Abeta-immunoreactive granules are located in astrocytes and not in microglia or neurons. Immunoelectron microscopy revealed that nonfibrillar Abeta immunoreactivity was located within lipofuscin-like granules in somewhat swollen astrocytes. These findings raise the possibility that astrocytes take up Abeta and attempt to degrade it in lysosomes in the aged brain.

Adult↗

Immunoradiometric assay for the N-terminal fragment of proatrial natriuretic peptide in human plasma.

Recently, the N-terminal fragment of proatrial natriuretic peptide (N-terminal proANP) has been proposed as a marker of chronic congestive heart failure. In this study, we established a two-step immunoradiometric assay using monoclonal antibodies and synthetic N-terminal proANP (1-67) as a standard. It allows us to measure plasma N-terminal proANP in only 4 h without prior extraction. The detection limit of this assay was 15 pmol/L for a 100 microL sample of plasma. Within-run CVs ranged from 1.7% to 2.9% and between-run CVs ranged from 4.2% to 5.1%. The dilution curves of plasma samples showed good linearity and analytical recovery was 89-104%. The mean (+/-SD) N-terminal proANP in plasma of 33 healthy subjects was 188 (+/-71) pmol/L and 1030 (+/-411) pmol/L in 25 patients with heart failure. Our immunoradiometric assay is rapid and precise enough for routine determination of N-terminal proANP in human plasma.

Antibodies, Monoclonal↗

Quantitation of amyloid beta-protein (A beta) in the cortex during aging and in Alzheimer's disease.

In this study we sought to learn about when and how amyloid beta-protein (A beta) accumulates in the cortex of normal individuals and about the difference in the A beta accumulation between normal aged and Alzheimer's disease (AD) brains. From consecutive autopsy cases and AD cases, hippocampus CA1 and occipitotemporal cortex T4 were sampled for A beta quantitation by the well characterized two-site enzyme immunoassays (EIAs). There was a strong tendency toward A beta 42 accumulation between the ages of 50 and 70 years in T4 and a little later in CA1. The A beta 42 levels were consistently higher in T4 than those in CA1 in any given case. The levels of A beta 42 in AD brains were significantly higher than those in control brains, and the extent of A beta 42 amino-terminal modification was also much greater in AD brains than that in control brains. Even in cases in which no senile plaques were immunocytochemically detected, EIAs clearly showed that significant amounts of A beta 42 already had accumulated. In contrast to A beta 42, A beta 40 showed no apparent age-dependent accumulation, and its high levels were found to be associated with AD.

Adult↗

[Vancomycin resistant enterococci].

Enterococci are normal intestinal flora in humans. Among enterococci, Enterococcus faecalis and Enterococcus faecium are frequently isolated and can become nosocomial pathogens in hospitals, especially in intensive care units and oncology wards. Recently, vancomycin-resistant enterococci (VRE) such as E. faecalis and E. faecium have caused a serious problem of hospital-acquired infections in Europe and the USA. VRE also has another aspect as a cause of community-acquired infections. Especially, avoparcin which had been used to enhance growth of food animals is documented as associated with the spread of VRE in European countries. In Japan, there have only been a few of reports about VRE so far. However, there evidence that VRE might become prevalent in many hospitals in Japan. In fact, we have already isolated another highly vancomycin-resistant E. faecium (VCM:MIC > 128 micrograms/ml) from a hospitalized diabetic patient. We should pay a careful attention to VRE and perform the following control measures: 1)re-education and re-training about hospital infection control procedures, 2) prudent use of vancomycin in clinical settings, 3)accurate report of VRE in clinical laboratories, and 4) good communications and collaborations among physicians, nurses and other health care personnel and laboratory technicians. We should learn more from countries in which VRE are already prevalent, and pursue further investigations, to prevent the spread of VRE in Japan.

Animals↗

[Introductory review of diagnostic approach to arteriosclerosis].

Investigation of the pathogenesis of arteriosclerosis and/or atherosclerosis has been progressed using molecular biology. New concepts have been developed and, receptors and substances have been found clinically and experimentally, which have led us to create new methods of evaluating or diagnosing the grade of atherosclerosis lesion. Dealing with the new concepts or knowledge in this symposium, this introductory paper describes an overview of pathogenesis of atherosclerosis, from which the new methods of evaluating or diagnosing lesion has been exploited. The injury to the endothelium leads to endothelial cell dysfunction, which initiates the acceleration of LDL oxidation and increases adherence of monocytes, macrophages and T lymphocytes, migrating subendothelially and causing large foam cells to develop because of lipid accumulation. Macrophages and platelets release many growth factors, which accelerate the growth of vascular smooth muscle cells, forming fibrous plaque. In these pathogenic processes of atherosclerosis, angiotensin II participates in releasing growth factor for cell proliferation and hepatocyte growth factor (HGF) participates in revascularization of the sclerotic lesion, suggesting a candidate marker for atherosclerosis. Hyperlipidemia and hypercoagulation are the major factors in advanced atherosclerosis. Using new methods to evaluate or diagnose lesions, further therapy and prevention for atherosclerosis will progress in future.

Arteriosclerosis↗

[Vascular endothelium-related factors and atherosclerosis/arteriosclerosis: serum hepatocyte growth factor as a possible indicator of vascular lesions].

To investigate the possible involvement of hepatocyte growth factor (HGF) with vascular lesions, we studied the relationship between serum HGF concentrations and the grades of retinal arteriosclerosis, coronary atherosclerosis proliferative changes in the retina of diabetic subjects, and activities of systemic vasculitis. Individuals with more advanced grades of retinal arteriosclerotic change showed higher serum HGF values (grade 0, 0.053 +/- 0.005 ng/ml ; grade 1, 0.144 +/- 0.022 ng/ml ; grade 2, 0.338 +/- 0.36 ng/ml ; grade 3, 0.526 +/- 0.051 ng/ml). The serum HGF concentration was increased in subjects with single- (0.200 +/- 0.012 ng/ml, double- (0.334 +/- 0.018 ng/ml) or triple- (0.379 +/- 0.022 ng/ml) vessel coronary heart diseases, compared with that in subjects with intact coronary arteries (0.112 +/- 0.008 ng/ml). Serum HGF in diabetes without retinopathy was lower than that in nondiabetic subjects (0.041 +/- 0.003 ng/ml vs 0.080 +/- 0.010 ng/ml, p < 0.05), but did not differ from that in other diabetic subjects with background retinopathy (0.058 +/- 0.007 ng/ml) or preproliferative retinopathy (0.048 +/- 0.010 ng/ml). Serum HGF was increased in patients with proliferative retinopathy without photocoagulation (0.213 +/- 0.025 ng/ml, p < 0.01), but not in those with photocoagulation (0.040 +/- 0.008 ng/ml). Serum HGF concentration was increased (p < 0.01) during the acute phase of Schönlein-Henoch purpura (0.31 +/- 0.15 ng/ml), a systemic vasculitis, but it returned to control levels during the remission phase (0.11 +/- 0.10 ng/ml). Increased serum HGF may be involved in the pathogenesis of arteriosclerosis/atherosclerosis, retinal neovascularization, or vasculitis, and measurement of serum HGF may be a useful test for predicting these vascular lesions.

Aged↗

Roles of brain angiotensin II and C-type natriuretic peptide in deoxycorticosterone acetate-salt hypertension in rats.

OBJECTIVE: To investigate the roles of brain angiotensin II and C-type natriuretic peptide (CNP) in the hypertensive mechanism of deoxycorticosterone acetate (DOCA)-salt hypertension. METHODS: We injected 50 microg/kg CV-11 974, an angiotensin II type-1 receptors antagonist, 30 nmol/kg CNP-22, or the vehicle (artificial cerebrospinal fluid) into the cerebral ventricle or intravenously 5 min before the intracerebroventricular infusion of 1.5 mol/I NaCl solution for 30 min into either male normotensive Wistar rats or DOCA-salt hypertensive rats anesthetized with urethane, and their arterial pressures and heart rates were continuously recorded. Blood (2 ml) was collected at the end of the infusion for the measurement of plasma concentration of arginine vasopressin. We infused 10 or 50 microg/kg per day CV-11 974, 10 or 50 nmol/kg per day CNP-22, or the vehicle (1 microl/h) into the cerebral ventricles of DOCA-salt hypertensive rats for 7 days by using osmotic minipumps, and measured their systolic arterial pressures, pulse rates, and urinary excretions of vasopressin. RESULTS: Intracerebroventricular pre-administrations of CV-11 974 and of CNP-22 inhibited increases in mean arterial pressure, heart rate, and plasma vasopressin concentration induced by intracerebroventricular infusion of 1.5 mol/l NaCl into normotensive rats; increases in hemodynamics and plasma level of vasopressin induced by intracerebroventricular infusion of 1.5 mol/l NaCl were suppressed by intracerebroventricular pre-injections of CV-11 974, but not of CNP-22, into DOCA-salt hypertensive rats. Continuous intracerebroventricular infusions of 50 microg/kg per day CV-11 974 attenuated hypertension in DOCA-salt treated rats, accompanied by a reduction in urinary excretion of vasopressin. Continuous intracerebroventricular infusions of 50 nmol/kg per day CNP-22, however, affected neither hypertension nor urinary excretion of vasopressin in DOCA-salt hypertensive rats. CONCLUSION: Brain angiotensin II could play a role in the pressor mechanism of DOCA-salt hypertension by increasing release of vasopressin via type 1 receptors. That brain CNP has an inhibitory effect on release of vasopressin in acute experiments indicates that the impairment of this inhibitory effect of brain CNP on secretion of vasopressin could be involved in the pathogenesis of DOCA-salt hypertension in rats.

Angiotensin II↗

[Usefulness of heart rate variability for evaluating cardiac autonomic nervous function].

To investigate the effect of gastric ulceration on cardiac autonomic nervous function, 24-hour ambulatory electrocardiograms were recorded in patients with artificial gastric ulcers caused by endoscopic treatment of gastric tumors. Their cardiac autonomic nervous activity was assessed by both time- and frequency-domain analyses of heart rate variability obtained from electrocardiogram recordings. The results were compared with those from patients who had undergone endoscopic treatment of esophageal varices or colorectal tumors, or gastrointestinal endoscopy alone. Parameters of time-domain analysis decreased significantly with the formation of gastric ulcers. Because parameters of frequency-domain analysis did not change in the group with gastric ulcers, this decrease in parameter of time-domain analysis suggests increased activity of cardiac sympathetic nervous system. There were no changes in the parameters of either time- or frequency-domain analysis in other groups. These results suggest that artificial gastric ulceration modifies cardiac sympathovagal balance, favoring cardiac sympathetic activity, while artificial esophageal and colon ulcers have no effect on cardiac autonomic nervous activity. Heart rate variability analysis is a useful method of evaluating possible implications between gastric ulceration and cardiac autonomic nervous function.

Aged↗

Molecular heterogeneity of hCGbeta--related glycoproteins and the clinical relevance in trophoblastic and non-trophoblastic tumors.

We analyzed immunoreactive hCG/hCGbeta (IR-beta) in the sera and urine of patients with trophoblastic diseases and non-trophoblastic tumors by using enzyme immunoassays (EIAs) specific for intact hCG, free hCG beta, and beta-core fragment of hCG (beta-CF). In trophoblastic diseases, while intact hCG and free hCGbeta were contained in both serum and urine, the beta-CF could be detected only in the urine of the patients. The relative contribution of the beta-CF to the total urinary IR-beta accounted for about 30-50% in normal early pregnancy and hydatidiform mole, and more than 60% in choriocarcinoma. We conclude that intact hCG should be measured in the serum rather than in the urine as a tumor marker for trophoblastic diseases, and suggested that the ratios of intact hCG, free hCGbeta, and beta-CF to each other may be useful indices in the differential diagnosis of trophoblastic diseases. Ectopic IR-beta was also investigated in the sera and urine of the patients with cervical, endometrial, ovarian, lung, and bladder carcinomas. We found that even when IR-beta could not be detected in the serum, the urine of the same patients with cancer often contained the significant amounts of IR-beta. The chromatographic study indicated that these urinary IR-beta were essentially attributed to beta-CF, leading to the evaluation of urinary beta-CF as a tumor marker. The positive rated of urinary beta-CF were 48% for cervical, 38% for endometrial, and 84% for ovarian, 40% for lung, and 42% for bladder carcinomas. We conclude that ectopic production of hCG beta by non-trophoblastic tumors is not a rare phenomenon and it can be recognized as a tumor marker when beta -CF is measured in urine of the patients.

Antibodies, Monoclonal↗

[Neovascularization and HGF: neovascularization in proliferative diabetic retinopathy and intraocular HGF].

Human hepatocyte growth factor (hHGF) has a strong angioneogenetic action. The present study was designed to investigate the possible involvement of hHGF in neovascularization in proliferative diabetic retinopathy by measuring vitreous hHGF concentration, and to examine the gene expression of hHGF in retinal Müller cells, which are presumed to play a role in proliferative diabetic retinopathy. Patients who had undergone pars plana vitrectomy were studied (33 diabetic patients with proliferative retinopathy and 20 nondiabetic subjects). The mean vitreous hHGF concentration was higher (p < 0.0001) in diabetic subjects with proliferative retinopathy (5.7 +/- 0.7 ng/ml) than in nondiabetic subjects (1.6 +/- 0.2 ng/ml). Furthermore, diabetic subjects with iris neovascularization, which is suggestive of advanced retinal ischemia, showed higher values of mean vitreous hHGF concentration than those without iris neovascularization (7.3 +/- 1.2 ng/ml [n = 14] vs. 4.5 +/- 0.7 ng/ml [n = 19], p < 0.01). Expression of hHGF gene was detected in cultured human Müller cells. Our results indicate that hHGF may be produced in the eye by retinal cells such as Müller cells and may play a role in neovascularization of proliferative diabetic retinopathy.

Diabetic Retinopathy↗