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Biomedical subjects

M Yoshioka

Publications and source records attributed to M Yoshioka.

At least 163 records · Page 9Linked to original sources

[Transient cerebral ischemia and long-term potentiation in the rat hippocampus].

Long-term potentiation (LTP) has been widely studied as a form of synaptic plasticity that represents a cellular mechanism of learning and memory. Among numerous processes and molecules that may be involved in LTP formation, a great many of them including neurotrophic and transcription factors have been described as those involved in neural death after ischemic insult. Nitric oxide (NO) is a molecule that is known to also exert double-edged effects on LTP formation. Here we will be describing recent advances with respect to the LTP mechanisms in the hippocampal synapses, a critical brain region for learning and memory function. In another context, we described our study elucidating the changes in hippocampal LTP as a functional response to transient cerebral ischemic insult, from the viewpoint of its relevance to NO production. As indices of NO production, nitrite and nitrate levels were determined by in vivo microdialysis. It was demonstrated that hippocampal LTP deficiency after transient cerebral ischemia was preceded by an increase in hippocampal NO production. Direct or indirect inhibition of an inducible NO synthase restored ischemia-induced LTP deficiency. These findings suggest that NO production, in part via inducible NO synthase, is responsible for LTP deficiency after transient cerebral ischemia in the rat hippocampus.

Animals↗

Rapid diagnosis at the outpatient clinic for breast tumors by fine needle aspiration cytology. The utility.

The aim of this study was to emphasize the utility and prove the accuracy of rapid diagnosis at the outpatient clinic for breast tumors by fine needle aspiration cytology [FNAC]. Rapid diagnosis for breast tumors by FNAC is performed on the same day just after mammography and echonography are carried out at our hospital and the result reported to the patients while they are waiting at the outpatient clinic. We evaluated FNAC by rapid diagnosis at the outpatient clinic for 1,786 breast tumors during the last ten years. The cases of no judgement (Class 0) were 11%, negative cases (Class I & II) 72%, suspicious cases (Class III) 7%, and positive cases (Class IV & V) 10%. We experienced only 4 false negative cases and 0 false positive cases among 1,198 cases during the last 5 years, whereas there were 8 false negative cases and 2 false positive cases among 588 cases during the first 5 years. Two false positive cases in the the first 5 years were judged as Class IV, but definitive surgery [mastectomy] was not performed because rapid diagnosis during the operation by frozen section confirmed no malignancy. As a result, all the cases in which mastectomies were performed up to now were confirmed malignant. We emphasize that rapid diagnosis at the outpatient clinic for breast tumors by FNAC is very useful for early detection and treatment and it is very important to consider the histological type of breast tumors by FNAC to prevent misjudgement.

Adult↗

Changes in the proliferative activities of cells in experimental atherosclerotic plaques during remodeling.

To investigate the relationship between cytologic alterations and cellular proliferation during atherosclerotic remodeling, we examined experimental atheromatous plaques by immunohistochemistry. Plaques were formed on rabbit aortas by cholesterol-enriched diets and mechanical stimulation over a period of 2 months. Plaques were examined 1 month and 6 months after induction. We used antibodies RAM-11, HHF-35, and monoclonal anti-proliferating cell nuclear antigen (PCNA) antibody for detection of macrophages (Mphi), smooth muscle cells (SMC), and PCNA, respectively. One month after induction, the plaques revealed a thickened intima with a fibrofatty histologic pattern or accumulation of foam cells. With either histologic pattern, foam cells were found to be Mphi and proliferative activity was mainly observed in Mphi. Six months after induction, calcification and organization were seen on the induced plaques, suggesting progression of remodeling. There were fewer Mphi and more SMC compared with plaques examined 1 month after induction. Proliferative activity was observed mainly in SMC. We have demonstrated that the proliferative activity of cell types changes during remodeling of atheromatous plaques. Our results suggest an important relationship between the proliferative activity of SMC and remodeling.

Animals↗

[Successful chemotherapy based on in vitro chemosensitivity testing in a case of recurrent thymic carcinoma].

A 71-year-old woman underwent radical resection in May 1994 for a mediastinal mass invading the anterior chest wall. Histopathological examination revealed adenosquamous cell carcinoma. She was treated with postoperative chemotherapy including 5-fluorouracil (5-FU) and 4'-D-tetrahydropyrayl-doxorubicin (THP), based on in vitro chemosensitivity testing (CST), by MTT assay, using a surgical specimen. In December 1994, a recurrent tumor was detected on the left anterior chest wall and the patient received two courses of 5-FU, THP and methotrexate (MTX). The size of the chest-wall tumor decreased 25%. In July 1995, the patient had involvement of the left axillary lymph node and brain metastases in addition to the mass on the chest wall. Therefore, cisplatin, 5-FU and MTX were selected as treatment agents, based on CST using a metastatic axillary lymph node. After two courses of these agents, chest computed tomography showed a 91% reduction in the size of the chest wall tumor. Radiation was administered for the brain metastasis. In March 1997, the patient died of thymic carcinoma.

Aged↗

Efficacy of a dentifrice containing 5% potassium nitrate and 1500 PPM sodium monofluorophosphate in a precipitated calcium carbonate base on dentinal hypersensitivity.

The effect on dentinal hypersensitivity from the use of a dentifrice containing 5.0% potassium nitrate, 1500 ppm sodium monofluorophosphate in a precipitated calcium carbonate (PCC) base over an eight-week period was compared to a placebo dentifrice without potassium nitrate. A total of forty-eight subjects were entered into the study and stratified into two balanced groups according to their baseline mean thermal (air blast) and tactile (Yeaple Probe) sensitivity scores. The two groups were randomly assigned to use either the potassium nitrate/PCC dentifrice or a placebo dentifrice without potassium nitrate. The two groups were well balanced with regard to their mean baseline thermal tactile sensitivity scores, sex and age. Subjects were instructed to brush their teeth twice daily (morning and evening) for one minute with their assigned dentifrice and a commercially available soft-bristled toothbrush. Dentinal hypersensitivity examinations, which included tactile and thermal sensitivity, were conducted at baseline, four weeks, and eight weeks. Examinations were conducted by the same dental examiner (TS) on the subjects at each examination. After four weeks' use of their assigned products, those subjects in the potassium nitrate/PCC dentifrice group demonstrated statistically significant improvements (p < 0.0001), as compared to the placebo dentifrice without potassium nitrate, in tactile and thermal sensitivity. After eight weeks' use of their assigned products, those subjects in the potassium nitrate/PCC dentifrice group again demonstrated statistically significant improvements (p < 0.0001), in tactile and thermal sensitivity, as compared to the placebo dentifrice without potassium nitrate. Thus it can be concluded from this study that the use of a dentifrice containing 5.0% potassium nitrate and 1500 ppm sodium monofluorophosphate in a precipitated calcium carbonate (PCC) base is a clinically effective method for reducing dentinal hypersensitivity.

Adult↗

[Surgical correction of complete rupture of the anterior papillary muscle complicating acute myocardial infarction].

A 71-year-old female patient with complete post infarction rupture of the anterior papillary muscle and severe congestive heart failure is presented. The diagnosis was determined by echocardiography and cardiac catheterization. Two days after the acute episode, the patient underwent emergency mitral valve replacement with an ATS 27 M prosthetic valve. The mitral annulus was edematous and friable. Postoperatively, the patient improved dramatically. In this case, two factors were important-repairing the nonfunctioning mitral valve as soon as possible and handling the friable mitral annulus with great care.

Aged↗

[Continuous arterial infusion of protease inhibitor with supplementary therapy for the patients with severe acute pancreatitis--clinical effect of arterial injection of ulinastatin].

We treated five patients with severe acute pancreatitis by continuous arterial infusion (CAI) of protease inhibitor, nafamostat mesilate. Arterial injection (AI) of ulinastatin was performed in four cases and AI of antibiotics (IPM/CS) was done in one case, as supplemental therapies of CAI. Abdominal pain disappeared in 7.9 hours on the average, abdominal tenderness disappeared in 5.0 days and laboratory data lately recovered. All five cases treated by these therapies were cured without hemodialysis or surgical treatment in acute phase. AI of ulinastatin through arterial infusion catheter is pharmacokinetically more effective, because it yields a relatively high concentration of the drug at the acting site when compared with that of intravenous injection. Furthermore ulinastatin inhibits different types of protease from nafamostat mesilate. Therefore the clinical effect of CAI of nafamostat mesilate is enhanced by the combined therapy with AI of ulinastatin. It is also suggested that arterial injection of ulinastatin might be effective for the control of abdominal pain and that arterial injection of antibiotics might have an advantage on prevention of infectious pancreatic necrosis.

Acute Disease↗

Bone mass loss due to estrogen deficiency is compensated in transgenic mice overexpressing human osteoblast stimulating factor-1.

Osteoblast stimulating factor-1 (OSF-1) stimulates in vitro proliferation and differentiation of osteoblastic cells, and its gene is expressed in the bone and brain tissues in mammals and amphibians. To evaluate the in vivo function of OSF-1 in bone metabolism, transgenic mice overexpressing the human osf-1 gene driven by the osteocalcin promoter were generated. Femoral bone mineral content was increased in transgenic mice relative to wild-type controls as estimated by ash assay, depending on the transgene copy number per cell. In ovariectomized mice, bone mass loss due to estrogen deficiency was observed in both transgenic and control mice but bone mass was still higher in transgenic mice than in controls. Bone mass in ovariectomized transgenic mice was comparable to that in wild-type mice without ovariectomy. These observations indicate that OSF-1 may direct in vivo appositional bone formation by increasing osteoblast activity rather than decreasing osteoclast activity, suggesting a new way to treat osteoporosis with OSF-1.

Animals↗

Antiemetic effects of N-3389, a newly synthesized 5-HT3 and 5-HT4 receptor antagonist, in ferrets.

The antiemetic activity of N-3389 (endo-3,9-dimethyl-3,9-diazabicyclo[3,3,1]non-7-yl-1 H-indazole-3-carboxamide dihydrochloride), a new 5-HT3 and 5-HT4 receptor antagonist, against cisplatin-, cyclophosphamide- and copper sulfate-induced emesis was investigated using ferrets. We also examined the effects of these agents on abdominal afferent vagus nerve activity in anesthetized ferrets. Both intraperitoneal (0.1-1.0 mg/kg) and oral (0.1-1.0 mg/kg) administration of N-3389 produced dose-dependent antiemetic effects. The time-course of cisplatin (10 mg/kg, i.p.)-induced emesis in another group of ferrets paralleled the increase in abdominal afferent vagus nerve activity induced by cisplatin (10 mg/kg, i.p.) and was inhibited by pretreatment with N-3389 (1.0 mg/kg, i.v.). Furthermore, the cisplatin (10 mg/kg, i.p.)-induced increase in abdominal afferent vagus nerve activity was markedly reduced by an additional injection of N-3389 (0.1-1.0 mg/kg, i.v.) in a dose-dependent manner. The antiemetic effects exhibited by N-3389 are probably due to the inhibition of 5-HT3 and 5-HT4 receptors on the abdominal afferent vagus nerves.

5-Methoxytryptamine↗

Expression of tumor necrosis factor-alpha in muscles of polymyositis.

We immunohistochemically examined biopsied muscles from nine untreated patients with polymyositis (PM) and five patients with other neuromuscular diseases (ONMD), using monoclonal antibodies to tumor necrosis factor-alpha (TNF-alpha) and lymphoid surface markers. In muscles of three patients with PM, we observed many TNF-alpha positive macrophages and lymphocytes in endomysium and around vessels in the muscles. By contrast, there were few, weakly TNF-alpha stained cells in muscles of three patients with ONMD. The ratio of TNF-alpha-positive cells to the muscle fibers and the ratio of TNF-alpha-positive cells to the mononuclear cells were significantly higher in PM compared with ONMD. In addition, we observed atrophic muscle fibers more frequently in TNF-alpha-positive muscles than TNF-alpha-negative ones. We conclude that, at least, in a part of PM patients, TNF-alpha produced locally may contribute to the pathogenesis of PM.

Adult↗

Physical properties of rabbit articular cartilage after transection of the anterior cruciate ligament.

The effect of unilateral transection of the anterior cruciate ligament on the confined compression and swelling properties of the distal femoral articular cartilage of skeletally mature rabbits at 9 weeks after surgery was determined. Gross morphological grading of the transected and contralateral control distal femora stained with India ink confirmed that cartilage degeneration had been induced by ligament transection. Osteochondral cores, 1.8 mm in diameter, were harvested from the medial femoral condyles. The modulus, permeability, and electrokinetic (streaming potential) coefficient of the articular cartilage of the osteochondral cores were assessed by confined compression creep experiments. The properties (mean +/- SD) of control cartilage were: confined compression modulus, 0.75 +/- 0.28 MPa; hydraulic permeability, 0.63 +/- 0.28 x 10(-15) m2/Pa*sec; and electrokinetic coefficient, 0.16 +/- 0.31 x 10(-9) V/Pa. In transected knees, the modulus was reduced by 18% (p = 0.04), while the permeability and electrokinetic coefficient were not detectably altered. The change in modulus was accompanied by a trend (p = 0.07) toward a decrease (-11%) in the glycosaminoglycan density within the tissue, a significant increase (p < 0.001) in the water content of the cartilage after equilibration in 1 x phosphate buffered saline from 70.3 +/- 4.1% in control knees to 75.2 +/- 4.0% in transected knees, and little further swelling after tissue equilibration in hypotonic saline. The compressive modulus of the cartilage from both control and transected knees was positively correlated with the density of tissue glycosaminoglycan. The alterations in the physical properties of the articular cartilage after transection of the anterior cruciate ligament in the rabbit show trends similar to those observed in human and other animal models of osteoarthritis and provide further support for the use of this model in the study of cartilage degeneration.

Animals↗

Dietary docosahexaenoic acid increases cerebral acetylcholine levels and improves passive avoidance performance in stroke-prone spontaneously hypertensive rats.

We have recently shown that inferior performance in passive avoidance task is accompanied with decreased hippocampal choline (Ch) in stroke-prone spontaneously hypertensive rats (SHRSP) compared with normotensive control Wistar-Kyoto rats (WKY). We also reported that dietary docosahexaenoic acid (DHA) suppresses the development of hypertension and stroke-related behavioral changes, resulting in the prolongation of the life span of SHRSP. In this study, we examined the effect of dietary DHA on the cerebral acetylcholine (ACh) levels and learning performance in passive avoidance tasks in SHRSP. The arachidonic acid decreased and the DHA increased in plasma lipids dose dependently with dietary DHA treatments, which decreased the systolic blood pressure in SHRSP. Dietary DHA significantly restored the significantly inferior learning performance in passive avoidance response observed in control SHRSP (DHA 0%). Furthermore, the hippocampal ACh levels were correlated positively with the total response latency in passive avoidance tasks. These results suggest that cholinergic dysfunction in the brain of control SHRSP is responsible, at least in part, for the impaired learning ability and the dietary DHA ameliorates this performance failure.

Acetylcholine↗

Association of interleukin-6 in the cerebrospinal fluid during crisis of calf with ammoniated feed syndrome.

Ammoniated feed syndrome (AFS) in cattle is a neurotoxic syndrome caused by feeding specific ammoniated forage. To clarify the pathophysiology of AFS, we examined the association of interleukin-6 (IL-6) in the brain. By feeding milk either from cows fed such ammoniated forage or milk added with 4-methyl-imidazole, newborn calves showed a neurotoxic crisis of hyperexcitability, ataxia, muscle tremor, circling, roaring, epileptoid seizure, sweating and marked fever response. Although these calves had no pathological lesions in the brain, we detected a rise in IL-6 in the cerebrospinal fluid (CSF). Tumor necrosis factor-alpha (TNF-alpha) was not detected in the CSF. In the sera, IL-6 and TNF-alpha hardly changed during the experiment. Administration of recombinant human IL-6 into the lateral ventricle resulted in fever. Thus, we believe IL-6 in the CSF is related to the fever response in newborn calves with AFS.

Acute Disease↗

Primary culture and expression of cytokine mRNAs by lipopolysaccharide in bovine Kupffer cells.

Kupffer cells are sessile tissue macrophages that have a role in liver defense against endogenous endotoxins. Because little information is available on the role of bovine Kupffer cells, we developed a primary culture method to investigate the function of bovine Kupffer cells. Kupffer cells were isolated from the caudate lobe of calf liver by perfusion with collagenase and pronase. Then, the cells were purified by gradient centrifugation followed by counterflow centrifugal elutriation. With the methods, a mean number of 1.5 x 10(6) Kupffer cells with a final viability of over 98% was obtained from 1 g of the liver. Over 95% of the isolated cells were positive for non-specific esterase activity and had surface molecule of CD68. The cultured Kupffer cells expressed mRNAs of tumor necrosis factor-alpha, interleukin (IL)-1 alpha, IL-1 beta and IL-6 by stimulation for 3 h with lipopolysaccharide. The primary culture of bovine Kupffer cells could be useful to investigate the systemic inflammatory response in bovine liver.

Animals↗

Effects of dietary docosahexaenoic acid on survival time and stroke-related behavior in stroke-prone spontaneously hypertensive rats.

1. Dietary docosahexaenoic acid (DHA) suppressed the age-dependent increase in systolic blood pressure and prolonged the average survival time of stroke-prone spontaneously hypertensive rats (SHRSP). 2. Dietary DHA (1% and 5% in diets) altered the circadian rhythm of SHRSP, causing significant increases in ambulatory activity during the dark period. At the onset of stroke, desynchronization with light and dark phases and new biological rhythms were noted in all of the control SHRSP (DHA 0%). DHA treated SHRSP did not show such behavioral changes. 3. These effects were accompanied by the increase of DHA and the decrease of AA levels in plasma and brain cortex. 4. It was concluded that dietary DHA suppresses the development of hypertension and stroke-related behavioral changes, resulting in prolongation of the SHRSP's life span.

Aging↗

Chiral analysis of 3-methoxy-4-hydroxyphenylglycol in human urine.

Since 3-methoxy-4-hydroxyphenylglycol (MHPG) is a neutral metabolite from norepinephrine, it will be a diagnostic marker for mental diseases such as depression. For the development of an immunoassay, the natural enantiomer of MHPG would be required to prepare its antigen and to examine the specificity of the antibody. A natural enantiomer synthesized, however, has not been obtained so far. In this paper, we attempted to enantioseparate synthetic DL-MHPG and to assign D-enantiomer from the optical rotation of MHPG purified from human urine, because endogenous norepinephrine occurs as D-enantiomer which should metabolically generate D-MHPG. Enantioseparation conditions were tested using a Ceramospher Chiral RU-1 column (4.6 x 250 mm) at a flow rate of 0.5 ml/min. The resolution was adequate for the analysis and purification of synthetic DL- and the urinary MHPGs using methanol as a mobile phase and the column temperature at 0 degrees C, where DL-MHPG was detected as two peaks. The earlier peak (peak 1) showed (-) optical rotation, while the latter gave (+) optical rotation. After being treated with beta-glucuronidase, the normal human urine was extracted with ethyl acetate and then evaporated to dryness. The residue was suspended in water and the supernatant was analyzed and purified by a reversed phase column with a multi channel detector. A peak corresponding to MHPG was collected and concentrated to dryness. The pooled residues were dissolved in methanol and enantioseparated on the chiral HPLC. The urinary MHPG appeared as a single peak which was corresponded to the earlier peak of DL-MHPG and showing (-) optical rotation. Thus, the urinary MHPG was found to be D-(-)-MHPG. Then the absolute configuration of enantioseparated MHPGs were assigned to each optical rotation, judging from the chemical data and the metabolic pathway of the urinary D-MHPG. These enantiomers will be useful for studying on biochemistry and immunoassay.

Chromatography, High Pressure Liquid↗