Biomedical subjects

M Nishida

Publications and source records attributed to M Nishida.

At least 307 records · Page 17Linked to original sources

PubMed1994

A Case of Stromal Sarcoma of the Breast Coexisting with Noninvasive Ductal Carcinoma.

This paper describes a very rare case of stromal sarcoma of the breast coexisting with simultaneous noninvasive ductal carcinoma in the same breast. A 75-year-old female was seen at our hospital for a lump in the right breast. On physical examination, a 10 x 8 cm well-difined and movable hard mass with a smooth surface was palpated in the upper outer quadrant of the breast. Aspiration cytology suggested a non-epithelial tumor with marked dysplasia (class 3b). Drill biopsy revealed probable stromal sarcoma. Simple mastectomy and axillary lymphonode sampling was performed. Histologically, the tumor was stromal sarcoma in the upper outer quadrant of the breast. In addition, noninvasive ductal carcinoma was simultaneously detected in the upper inner quadrant of the breast as an independent lesion. No positive axillary nodes were found. To date, as far as we could investigate, there was no preceding case report of both stromal sarcoma and carcinoma in the single patient at the same time.

Journal Article↗

PubMed1994

Tumorigenicity of BALB3T3 A31 cells transfected with hamster-complement-C1s cDNA.

Hamster-complement-C1s cDNA was inserted into an expression plasmid BCMGSNeo (BCMGSNeoHACS). BALB/c mouse fibroblast A31 cells, which do not produce C1s, were transfected with BCMGSNeoHACS and the transfectants were selected with G418. Normal C1s production by the transfectants was confirmed by Northern and immunoblot analysis and by an esterase assay. To examine the tumorigenicity of the transfectants, 1 x 10(6) cells were injected s.c. into 6-week-old BALB/c nu/nu mice. Three C1s cDNA transfectants (A3CS9, A3CS12, A3CS13) formed tumors whereas both A31 and A31 transfected with the vector alone (A3BCM1 and A3BCM3) did not. The tumors derived from the transfectants showed invasive growth, and many capillaries were observed in the tumors. A tumor derived from A3CS13 was examined immunohistochemically and found to be reactive with an anti-C1s monoclonal antibody. Tumor cells were cultured in vitro again and C1s secreted into the culture medium was examined by immunoblot analysis. C1s synthesized by the tumor cells derived from A3CS13 maintained its biological functions. Tumor cells derived from A3CS9 and A3CS12 cells, however, produced C1s having abnormal disulfide bonds.

3T3 Cells↗

PubMed1994

Mutation of K-ras protooncogene is associated with histological subtypes in human mucinous ovarian tumors.

A series of 57 mucinous and 47 serous ovarian tumors (adenomas, tumors of borderline malignancy, and carcinomas) were examined by polymerase chain reaction-single strand conformation polymorphism analysis and direct sequencing for mutations in codons 12, 13, and 61 of K-ras gene. Higher incidence of K-ras mutations was observed in mucinous tumors compared to serous ones. Mutations were detected in 4 of 30 mucinous adenomas (13%), in 4 of 12 mucinous tumors of borderline malignancy (33%), and in 7 of 15 mucinous carcinomas (46%). Only 1 of 17 serous carcinomas (6%) had a mutation of K-ras in serous ovarian tumors. All mutations identified were in codon 12. Detailed analysis revealed that more K-ras mutations in mucinous adenomas were observed in intestinal type (identified in 4 of 13) than in endocervical type (identified in 0 of 17). Thus, K-ras gene codon 12 mutations in mucinous ovarian adenomas appear to be associated with the occurrence of intestinal type adenomas.

Adenocarcinoma, Mucinous↗

PubMed1994

Histological changes of implanted collagen material during bone induction.

Studies were made on the fate of implanted material during bone induction. Mixtures of 1 mg of crude bone morphogenetic protein (BMP), or bovine serum albumin as a control, and 1.5 mg of bovine collagen, were pressed into discs and implanted under the fascia of the rectus abdominus muscle of rats. The tissues with implants were fixed 7, 10, and 14 days later and examined histologically. On day 7 after implantation, the implant was surrounded and invaded by alkaline phosphatase-positive cells. New bone and cartilage were seen at the periphery of the implant. In the regions of calcified cartilage and bone, these osteogenic matrices were intermixed with the implant. The mineral deposits were seen by electron microscopy not only on the osteogenic matrices but also on the implanted collagen. On day 14, the bone had spread to the center of the implant. No osteogenesis or chondrogenesis was seen in control implants. It was concluded that the calcification occurred on the implanted collagen during bone induction, and that it was related to successive bone formation and remodeling.

Alkaline Phosphatase↗

PubMed1994

Increased actin cable organization after single chromosome introduction: association with suppression of in vitro cell growth rather than tumorigenic suppression.

We previously showed that introduction of a single human chromosome 1, 6, or 9 derived from normal fibroblasts into HHUA endometrial carcinoma cells resulted in suppression of tumorigenicity. The tumorigenic suppression was accompanied by remarkable morphological changes in the microcell hybrids containing an extra copy of chromosome 1. The study presented here was undertaken to search for target cytoskeletal components affected by chromosome 1 transfer into endometrial carcinoma cells. We found that the microcell hybrids containing an extra copy of chromosome 1 were characterized by intracellular actin bundle formation and an excessive accumulation of actin and vinculin. The latter was a result of increased stabilization of the proteins. Additionally, chromosome 3 introduction into RCC23 human renal carcinoma cells resulted in prolongation of cell division and in senescence of a significant proportion of the microcell hybrids. In these microcell hybrids, the intracellular actin network was also reorganized, but the amounts of actin and vinculin protein were not increased. These findings suggest that the increased actin organization, which appeared not to cause tumorigenic suppression in the microcell hybrids, is associated with complementation of tumor suppressor genes and senescence by multiple mechanisms.

Actin Cytoskeleton↗

PubMed1994

Intraarterial combined immunochemotherapy for unresectable hepatocellular carcinoma: preliminary results.

An important objective for patients with unresectable hepatocellular carcinoma (HCC) is the development of effective chemotherapy. We administered a combination of biological response modifiers and anticancer agents to 24 patients with unresectable HCC. Each case had an implanted infuser port which was connected to a catheter placed in the hepatic artery for the intraarterial (i.a.) administration of chemotherapy. The following agents were administered to each patient: recombinant interleukin-2 (800,000 JRU/day infused i.a. continuously for 6 days/week); OK-432 (5 KE injected i.a. twice in 4 weeks and i.m. three times per week); Adriamycin (10 mg injected i.a. twice in 4 weeks); cyclophosphamide (300 mg injected i.a. twice in 4 weeks), and famotidine (40 mg/day administered orally). Objective response was assessed according to tumor size measured by computed tomography and angiography before and after treatment. We observed a complete response (CR) in 4, partial response (PR) in 3, minor response (MR) in 7, no change (NC) in 7, and progressive disease (PD) in 3. The response rate (CR+PR+MR) was 58.3%. The overall 2-year survival rate was 52%. The 2-year survival rate of the responders (CR+PR+MR) was 80%, while that of the non-responders (NC+PD) was 0%. There was a significant difference between the responders and non-responders in respect to survival rate (P < 0.05). The percentages of CD25+ cells, CD56+ cells, and Leu7-CD16+ cells and NK activity in the peripheral blood showed a significant increase following the regimen. Serum levels of tumor necrosis factor alpha TNF alpha rose after the initiation of OK-432. TNF alpha levels were higher in the responders than in the non-responders. Adverse effects included high fever (all patients) and severe transient hypotension (15 patients) that was controlled by conservative therapy. Combined immunochemotherapy administered intraarterially may be a new strategy for treating unresectable HCC.

Aged↗

PubMed1994

Contribution of visceral fat accumulation to the development of coronary artery disease in non-obese men.

Associations between intra-abdominal visceral fat accumulations and coronary risk factors were studied in a sample of 29 non-obese men aged 57 +/- 10 years with coronary artery disease (CAD). Their body mass indexes (BMI) were 23.8 +/- 1.5 (range 18.7-26.3). The visceral fat area (VFA) and the subcutaneous fat area (SFA) were measured at the level of the umbilicus by computed tomography. In patients with CAD, the average VFA was significantly increased compared with that in 54 control subjects without CAD, matched for sex, age, and BMI (117.2 +/- 53.1 vs. 93.8 +/- 38.6 cm2, P < 0.05). However, their average SFA was not statistically different (111.2 +/- 33.3 vs. 106.3 +/- 35.7 cm2, N.S.). Eleven CAD patients (38%) and nine control subjects (17%) had greater than 2 S.D. higher than the mean VFA obtained from 22 healthy subjects extracted from the control subjects. Accordingly, the proportion of the subjects with high VFA was significantly higher in the CAD group. This group also had significantly higher levels of plasma glucose and insulin areas than controls determined by oral glucose tolerance tests. This may be due to insulin resistance. The proportion of the subjects with multiple risk factors including hyperlipidemia, hyperglycemia, and hypertension was significantly higher in the CAD patients with high VFA compared with the control subjects with normal VFA (CAD with high VFA 82% and control with normal VFA 33%). These findings suggest that visceral fat accumulations may play an important role in the occurrence of CAD regardless of obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1994

Marked reduction of pancreatic insulin content in male ventromedial hypothalamic-lesioned spontaneously non-insulin-dependent diabetic (Goto-Kakizaki) rats.

The effects of ventromedial hypothalamic (VMH) lesions were examined in male and female non-obese non-insulin-dependent diabetic (Goto-Kakizaki [GK]) rats with respect to glucose metabolism and pancreatic insulin content. VMH lesions produced hyperphagia and hyperinsulinemia in both male and female GK rats. In male rats, plasma glucose levels of VMH-lesioned GK rats (22.7 +/- 3.1 mmol/L) were significantly greater than the levels of sham-operated GK rats (10.6 +/- 1.0 mmol/L, P < .001) at 7 weeks after the operation, although there were no differences in these levels between VMH-lesioned and sham-operated groups in Wistar rats. Plasma insulin levels in male VMH-lesioned GK rats tended to be lower at 7 weeks than at 1 week. VMH lesions caused a significant decrease in the pancreatic insulin content of male GK rats (12.0 +/- 2.3 nmol/L/g pancreas) compared with male sham-operated rats (15.8 +/- 1.4 nmol/L/g pancreas, P < .05) 9 weeks postoperatively. In contrast to the results in male rats, female GK rats showed no differences in plasma glucose levels between VMH-lesioned and sham-operated groups at 7 weeks. Female VMH-lesioned GK rats also showed no difference in plasma insulin levels between 1 week and 7 weeks. The pancreatic insulin level of female VMH-lesioned GK rats was unchanged from that of female sham-operated GK rats. The insulin content was significantly greater in the VMH-lesioned Wistar group than in the sham-operated Wistar group, regardless of sex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Primary pineal melanoma with long-term survival: case report.

A rare case of primary pineal melanoma is reported. The patient was a 53-year-old woman who complained of a severe headache. Computed tomography and magnetic resonance images revealed obstructive hydrocephalus caused by a mass lesion in the pineal region. A biopsy was performed through an occipital transtentorial approach. A black pigmented solitary tumor was seen without leptomeningeal dissemination. Histologic examination revealed melanoma. Chemotherapy consisting of dacarbazine, ACNU, vincristine, and interferon was used. Follow-up imaging studies showed dramatic reduction of the tumor without recurrence for 4 years. This report demonstrates that a solitary primary intracranial melanoma without leptomeningeal dissemination and with rare mitoses may yield a good result with chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Polymorphonuclear leukocytes-induced injury in hypoxic cardiac myocytes.

Growing evidence suggests that free radicals derived from polymorphonuclear leukocytes (PMNs) play an important role in myocardial ischemia-reperfusion injury. To elucidate the cellular mechanism by which activated PMNs exacerbate ischemic myocardial damage, we investigated the extent of cell injury, assessed by the morphological deterioration, free radical generation, and lipid peroxidation in mouse embryo myocardial cells coincubated with activated PMNs. The generation of PMN-derived free radicals was related to the extent of myocardial cell injury. When myocardial cell sheets were subjected to hypoxia and glucose-free media, myocardial cells were injured (cristalysis in the mitochondria and disruption of the sarcolemma) after adding various PMN activators, and the injury extended to the adjacent cells. Chemiluminescent emission and production of thiobarbituric acid-reactive substances in the coincubated cells increased markedly compared with myocardial cells or PMNs alone. The augmented lipid peroxidation coincided with the progression of myocardial cell injury. Catalase inhibited the myocardial cell injury by 52%, the chemiluminescence by 46%, and lipid peroxidation by 50%, whereas superoxide dismutase exhibited less pronounced inhibition. These results indicate that a chain reaction of lipid peroxidation in myocardial cells induced by PMN-derived free radicals closely correlates with membrane damage and contributes to the propagation of irreversible myocardial cell damage.

Animals↗

PubMed1994

Adenosine blockade during reperfusion reverses the infarct limiting effect in preconditioned canine hearts.

OBJECTIVES: The aim was to investigate whether adenosine release after reperfusion contributes to infarct limitation by ischaemic preconditioning. METHODS: Dogs underwent preconditioning with four 5 min cycles of left anterior descending coronary artery (LAD) occlusion and reperfusion, followed by 90 min LAD occlusion and 5 h reperfusion with or without the non-specific adenosine receptor blocker, 8-phenyltheophylline (8-PT). Infarct size was assessed by a dual staining method with triphenyltetrazolium chloride and Evans blue. Blood flow measurements in the subendocardial region were made by infusion of coloured microspheres before occlusion and midway through the sustained occlusion. Transcardiac alteration of neutrophillic function was assessed by luminol-enhanced whole blood chemiluminescence induced by zymosan. RESULTS: Infarct size was significantly reduced in the preconditioned dogs [12.5(SEM 4.0)%, n = 10, p < 0.01] compared with the control dogs [40.5(6.1)%, n = 10], an effect significantly reduced by the 8-PT treatment [23.4(4.9)%, n = 8]. Treatment with 8-PT without ischaemic preconditioning had no effect on infarct size [42.8(6.3)%, n = 7]. There was no difference in myocardial blood flow in the ischaemic or non-ischaemic subendocardial tissue between any pair of the four groups. The ratio of whole blood chemiluminescence in the cardiac vein to that in the carotid artery was considerably reduced in preconditioned dogs compared with that in control dogs after reperfusion. Myeloperoxidase activity in the ischaemic myocardium and the peripheral neutrophil count at the end of the experiment were both also decreased compared with control dogs. In preconditioned dogs treated with 8-PT, neutrophillic function in the coronary circulation after reperfusion was increased compared with that in both controls and preconditioned dogs with no 8-PT treatment. There was no difference in neutrophillic function between the 8-PT-treated dogs with or without ischaemic preconditioning. Treatment with 8-PT increased myeloperoxidase activity in the ischaemic myocardium of the preconditioned dogs, and no difference was seen in activity between dogs treated with 8-PT with or without ischaemic preconditioning. CONCLUSIONS: An adenosine receptor blocker caused a moderate but significant reversal of infarct limitation by ischaemic preconditioning associated with a significant increase of neutrophillic function in the coronary circulation during early reperfusion.

Animals↗

PubMed1994

The presence of low molecular weight germinative substances in Bacillus cereus T spore extract.

An extract from intact spores of Bacillus cereus T having a germination-inducing activity was studied. Two distinct germinative principles were found through dialysis of the extract. One was diffusible through the dialysis membrane and the other was non-diffusible. The activity of the former fraction was inhibited by the addition of 1 mM glycoletherdiamine-N,N,N',N'-tetraacetic acid (GEDTA), whereas the latter fraction was inactive unless GEDTA was added to the assay system. The diffusible principle maintained the major portion of the activity found in the crude spore extract. By means of high-performance liquid chromatography (HPLC) using a gel permeation chromatography column, 9 fractions were obtained from the deproteinized diffusible fraction. Of those fractions, two fractions (No. 1 and No. 8) were responsible for the germination-inducing activity, but no reconstituted activity was observed unless both fractions No. 1 and No. 8 were added to the assay system. Amino acid analysis of fraction No. 1 revealed that the fraction was rich in free amino acids, especially in alanine. On the other hand, by the use of reverse-phase HPLC and fast atom bombardment mass spectrometry, it was concluded that the effective substance in fraction No. 8 was inosine. Based on these findings, it was suggested that the active substances in fraction No. 1 might be a free amino acid such as L-alanine and/or Ca2+ and a Ca(2+)-binding substance.

Alanine↗

PubMed1994

[Formation of drug-induced serotype variants of Pseudomonas aeruginosa: changes in biochemical properties, drug susceptibility and outer membrane proteins].

The serotype variants were formed in some isolates of Pseudomonas aeruginosa in the presence of anti-pseudomonal drugs in vitro. Pyocin type, various biochemical properties and drug susceptibility of these variants were compared with those of the parent cells. Furthermore, the patterns of outer membrane proteins were also examined for some respective parent and variant cells by the SDS-PAGE and compared with their drug susceptibilities. In P. aeruginosa No. 1-S (serotype E) and No. 1-R (serotype C), simultaneously isolated from the identical specimen of the infectious patient, the serotype variants were formed by anti-pseudomonal drugs and accompanied by changes in pyocin types, some biochemical properties and susceptibilities to various kinds of anti-pseudomonal drugs. When the profiles of outer membrane proteins of P. aeruginosa No. 1-R parent and two variant cells were evaluated by the SDS-PAGE, the quantitative differences of the porin proteins between the parent and variant cells were well related to their drug susceptibilities. Although eight variant cells with other serotype were formed from the parent cells (serotype A) of P. aeruginosa No. 13, four variants with serotype M and one non-typable variant showed changes in drug susceptibility such as resistance to imipenem only and no changes in biochemical properties. On the other hand, three other variants showed marked changes in two kinds of biochemical properties and in susceptibilities to various kinds of anti-pseudomonal drugs. From the results of SDS-PAGE, it was found that the porin protein profiles of outer membranes of these parent and variant cells except a few cells which corresponded to their drug susceptibility.

Anti-Bacterial Agents↗

PubMed1994

[Alteration of serotype and drug susceptibility of some Pseudomonas aeruginosa isolates by exposure to human serum and polymorphonuclear leukocytes].

In the presence of 40% human serum plus polymorphonuclear leukocytes (PMNs, 10(7) cells/ml), changes in the surface properties of clinical isolates of P. aeruginosa were investigated by determining their serotypes and pyocin types as the markers. Furthermore, three isolates were tested for their susceptibility to anti-pseudomonal drugs and profiles of outer membrane proteins by the SDS-PAGE analysis. P. aeruginosa No. 21 which did not change in serotype and pyocin type after exposure to serum plus PMNs did not alter their susceptibility to all the drugs tested or their profiles of OMPs. In the case of P. aeruginosa No. 1-S, the variants with different serotypes were formed after the exposure, and increased their susceptibilities to some beta-lactams and norfloxacin which could penetrate into the bacterial cells through the porin channels of the outer membrane. Furthermore, two of the three type variants formed decreased their susceptibilities to gentamicin and polymyxin B which penetrated into the cells by the self-promoted uptake pathway. P. aeruginosa No. 1-R formed the serotype A and G variants with different pyocin types, only when exposed to serum plus PMNs for 24 hours, and the results were accompanied by the appearance of the porin D2 which was not detected in the parent cells. A small number of P. aeruginosa formed the variants with different serotypes and pyocin types owing to the alteration of their surface structures, when the cells were exposed to serum plus PMNs. The alterations were accompanied by the changes in some outer membrane proteins and the drug susceptibility to anti-pseudomonal drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

PubMed1994

Calcium overload and cardiac myocyte cell damage induced by arachidonate lipoxygenation.

The accumulation of arachidonic acid and lipoxygenase metabolites of arachidonate occurs in ischemic-reperfused myocardium. Although lipoxygenase inhibitors have been shown to attenuate myocardial infarct size after ischemia-reperfusion, the relationship between arachidonate lipoxygenation and myocardial injury remains unclear. To investigate the direct effect of arachidonate lipoxygenation on cardiac myocytes, isolated rat cardiac myocytes loaded with indo 1 were superfused with Tyrode solution containing arachidonic acid mixed with soybean lipoxygenase. Although neither arachidonic acid nor lipoxygenase alone had any effects, arachidonic acid plus lipoxygenase induced an increase in the twitch amplitude associated with an increased intracellular Ca2+ concentration ([Ca2+]i) and irreversible hypercontracture. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, blocked these effects. Linolenic acid, which is also a lipoxygenase substrate, caused the same effects as arachidonic acid in the presence of lipoxygenase, whereas oleic and stearic acid, which do not function as lipoxygenase substrates, did not. Both ascorbic acid and alpha-tocopherol attenuated an increase in [Ca2+]i and the cellular damage, whereas nicardipine and superoxide dismutase had no effects. These results suggest that lipoxygenase metabolites of arachidonic acid cause intracellular Ca2+ overload and cellular damage to cardiomyocytes, probably through augmentation of lipid peroxidation of the cell membranes by free radicals.

Animals↗

PubMed1994

Ebselen protects against ischemia-reperfusion injury in a canine model of myocardial infarction.

We investigated the infarct-limiting effect of a selenoorganic compound, ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], in a canine coronary artery occlusion-reperfusion model of myocardial infarction. Ebselen, administered 1 h before coronary artery occlusion (50 mg/kg po), significantly reduced infarct size resulting from 90-min coronary artery occlusion followed by 5-h reperfusion (P < 0.05). When we examined the relation between infarct size and plasma ebselen level, infarct size in dogs with plasma ebselen level > 5 microM before reperfusion was significantly smaller (P < 0.05) than that in dogs with plasma ebselen level < or = 5 microM or in the control dogs. This infarct limitation produced by ebselen treatment was associated with an increase in reduced glutathione content and a reduction in myeloperoxidase activity in the ischemic myocardium. No differences between the control and treated groups were found in hemodynamic parameters or regional myocardial blood flow in the course of the experiment. The findings of this study demonstrate that ebselen effectively reduced the myocardial ischemia-reperfusion injury associated with preservation of the glutathione redox state and a reduction in neutrophil infiltration into the ischemic myocardium.

Animals↗

PubMed1994

Induction of manganese superoxide dismutase in rat cardiac myocytes increases tolerance to hypoxia 24 hours after preconditioning.

Manganese superoxide dismutase (Mn-SOD) is induced in ischemic hearts 24 h after ischemic preconditioning, when tolerance to ischemia is acquired. We examined the relationship between Mn-SOD induction and the protective effect of preconditioning using cultured rat cardiac myocytes. Exposure of cardiac myocytes to brief hypoxia (1 h) decreased creatine kinase release induced by sustained hypoxia (3 h) that follows when the sustained hypoxia was applied 24 h after hypoxic preconditioning (57% of that in cells without preconditioning). The activity and content of Mn-SOD in cardiac myocytes were increased 24 h after hypoxic preconditioning (activity, 170%; content, 139% compared with cells without preconditioning) coincidentally with the acquisition of tolerance to hypoxia. Mn-SOD mRNA was also increased 20-40 min after preconditioning. Antisense oligodeoxyribonucleotides corresponding to the initiation site of Mn-SOD translation inhibited the increases in the Mn-SOD content and activity and abolished the expected decrease in creatine kinase release induced by sustained hypoxia after 24 h of hypoxic preconditioning. Sense oligodeoxyribonucleotides did not abolish either Mn-SOD induction or tolerance to hypoxia. These results suggest that the induction of Mn-SOD in myocytes by preconditioning plays a pivotal role in the acquisition of tolerance to ischemia at a later phase (24 h) of ischemic preconditioning.

Adaptation, Physiological↗

PubMed1994

Cavernous sinus cavernoma treated with radiation therapy--case report.

A 71-year-old female presented with a syncopal attack. She underwent surgery for what appeared to be a meningioma. However, a small incision in the dura mater caused severe bleeding. Histological examination of the biopsy specimen showed sinus cavernoma with an incomplete pseudocapsule. The dura mater encapsulated the cavernous sinus cavernoma, explaining the severe bleeding from the dural incision. She was treated with Linac irradiation (40 Gy) which resulted in a decrease in tumor size. Radiation therapy is indicated for the treatment of cavernous sinus cavernoma, especially if associated with severe intraoperative bleeding.

Aged↗