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Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 469 records · Page 26Linked to original sources
PubMed1997

Spindle cell carcinoma of the breast: a case report and an immunohistochemical study including p53 and Ki-67 expression.

A rare case of spindle cell carcinoma (SpCC) of the breast occurring in a 51-year-old Japanese woman is reported. A firm and well-circumscribed tumor, measuring 9 x 8.5 x 8.5 cm, was located on the upper lateral region of the right breast. Microscopically, the tumor consisted of sheets of both malignant spindle cells and poorly differentiated ductal carcinoma containing squamoid islands with gradual transition to the spindle cell component. The immunocytochemical expression of epithelial markers was recognized in the spindle cells, as well as in the carcinomatous cells. Moreover, the spindle cell component expressed vimentin, alpha-smooth muscle actin and S-100 protein. Ultrastructurally, in addition to the features of adenocarcinoma, squamous or myoepithelial differentiation was confirmed in the spindle cell component. These findings thus suggest an epithelial origin with squamous differentiation and myoepithelial participation in the genesis of SpCC. In a comparative study, the expression of p53 protein and Ki-67 as a proliferation marker in each component of this tumor was also investigated. The mean p53 labeling index (LI) in both the carcinomatous and spindle cell area was similar, however the mean MIB-1 LI in the spindle cell area was significantly higher than that in the carcinomatous area. The results indicate that p53 overexpression is involved in the tumorigenesis of both components in the SpCC, and the spindle cell component shows a higher degree of proliferative activity than the carcinomatous component.

Biomarkers↗
PubMed1997

Heterogeneous actions of vasopressin on ANG II-sensitive neurons in the subfornical organ of rats.

The aim of this study was to investigate the effects of the antidiuretic hormone arginine vasopressin (AVP), which is released in vivo during dehydration and hypovolemia to prevent further water loss, on the activity of neurons in the subfornical organ (SFO). The SFO is a brain structure with an open blood-brain barrier and is critically involved in angiotensin II (ANG II)-dependent water intake. SFO neurons were recorded extracellularly in tissue slices of the rat brain and were tested for responsiveness to AVP and ANG II. About one-half of 159 neurons tested with an AVP concentration of 10(-6) M in the superfusion medium were responsive, and approximately equal proportions were excited and inhibited. Neurons exhibiting the different response types did not differ from each other with respect to spontaneous discharge rate, latency, and duration of the response. Excitatory and inhibitory responses to AVP were dose dependent and reversible, and their threshold concentrations (10(-8) to 10(-9) M) were similar. Superfusion with a medium low in Ca2+ and high in Mg2+ showed that the excitatory effect is most likely direct, whereas the inhibitory effect largely depends on inhibitory synaptic interaction. About one-half of the SFO neurons excited by ANG II (10(-7) M) were responsive to AVP (10(-6) M), and equal proportions were inhibited and excited. Both excitatory and inhibitory AVP actions were blocked by the V1-receptor antagonist, Manning compound, and neurons responsive to AVP did not respond to the V2-receptor agonist [deamino-Cys1,D-Arg8]vasopressin. It is concluded that AVP, probably released from synaptic terminals, may increase or decrease the activity of neurons in the SFO, many of which are activated by ANG II. In contrast to previous experiments on ducks, in which the exclusively excitatory effect of the avian antidiuretic hormone arginine vasotocin on ANG II-sensitive SFO neurons correlates well with the dipsogenic effect of both peptides, a greater functional heterogeneity exists among AVP-responsive neurons in the rat SFO.

Angiotensin II↗
PubMed1997

In vitro macro- and microautoradiographic localization of V1 and V2 receptors in the rat kidney using OPC-21268 and OPC-31260.

To elucidate the precise localization of vasopressin (VP) V1 and V2 receptors in the kidney, we utilized in vitro macroautoradiography (macro-ARG) and microautoradiography (micro-ARG) of these receptors in Wistar rat kidneys. This was done by using OPC-21268 and OPC-31260, two newly developed selective V1 (OPC-21268) and V2 (OPC-31260) receptor antagonists. For macro-ARG, 10-microm kidney sections were incubated with Tris-HCl buffer containing [3H]-VP with or without unlabeled ligand (VP, OPC-21268, or OPC-31260) at 20 degrees C for 40 min. These sections were then loaded into X-ray cassettes with Hyperfilm-[3H] and exposed in the dark for 2 months. The autoradiograms were quantitatively analyzed by using the research analysis system RAS 1,000; the V1 and V2 receptors were quantitated by subtracting the nonspecific binding (incubated with OPC-21268 and OPC-31260, respectively) from the total binding. To assess a more precise localization of the V1 and V2 receptors, we also investigated the micro-ARG of the renal V1 and V2 receptors by dipping the kidney section slides used for macro-ARG into a photographic emulsion and observing the receptors under light microscopy. [3H]-VP binding to the rat kidney was completely displaced by unlabeled excess VP, but not by unlabeled angiotensin II, indicating that [3H]-VP binding was specific for VP receptors. Computerized quantification showed that V2 receptors, visualized by OPC-31260, were the predominant type of VP receptor in the kidney. Conversely, V1 receptors, visualized by OPC-21268, were fewer in number. V1 receptors were partly localized to the glomerulus, cortical vessels, interstitial cells, and the medullary vessels. The V2 receptors localized to the collecting ducts and medullary tubules. Our findings indicated that renal V1 and V2 receptors can be detected by in vitro macro- and micro-ARG by using OPC-21268 and OPC-31260.

Animals↗
PubMed1997

Responses of monkeys with pollinosis to two major allergens of Japanese cedar pollen.

We examined the responses of two Japanese monkeys with pollinosis to two major allergens (Cry j 1 and Cry j 2) of Japanese cedar pollen. The two monkeys (A and B) had specific IgE antibodies to the allergens and showed a strong positive reaction to both of them in the intradermal test. In the histamine release test with peripheral blood mononuclear cells (PBMC), monkey A showed a typical pattern similar to that seen in human patients, while monkey B released a low level of histamine. The proliferative response of PBMC to both allergens in monkey A was weak, but was typical in monkey B. From clinical as well as immunological points of view, these monkeys may be a suitable animal model for Japanese cedar pollinosis in humans.

Allergens↗
PubMed1997

Role of activin-A and follistatin in foam cell formation of THP-1 macrophages.

Macrophage (M phi) foam cell formation is a characteristic event that occurs in the early stage of atherosclerosis. To examine the roles of activin-A, a member of the transforming growth factor-beta superfamily, and follistatin, the binding protein for activin-A, in M phi function, we investigated their effects on foam cell formation of THP-1 M phi s. When THP-1 M phi s were treated with activin-A (5 nmol/L), foam cell formation and cellular cholesteryl ester accumulation were decreased. This downregulation was paralleled by a reduction in cell association and degradation of acetylated LDL. The inhibitory effect of activin-A on cell association and degradation was dose dependent, and the effect was blocked by concomitant addition of follistatin. Activin-A (5 nmol/L) also decreased the Bmax for acetylated LDL and scavenger receptor mRNA expression. Follistatin showed an effect opposite to that of activin-A and promoted M phi foam cell formation and cellular cholesteryl ester accumulation. It increased binding, cell association, and degradation of acetylated LDL and upregulated scavenger receptor mRNA expression. Because follistatin is the binding protein for activin-A, follistatin's effect is considered to be mediated by blocking the inhibitory effect of intrinsic activin-A. These results indicate that activin-A inhibits and follistatin promotes M phi foam cell formation by regulating scavenger receptor mRNA expression. We conclude that activin-A and follistatin play important roles in the process of atherosclerosis by regulating M phi foam cell formation.

Activins↗
PubMed1997

Magnetic resonance imaging in diagnosis of right coronary arteriovenous fistula--a case report.

We describe a patient with a right coronary arteriovenous fistula in whom magnetic resonance imaging (MRI) was useful in establishing the diagnosis. In a 36-year-old woman, T1 spin echo MRI demonstrated a massively dilated coronary arteriovenous fistula connecting the right coronary artery to the right atrium. The cine field echo technique showed a continuous shunt flow within the fistula as documented by the flow void throughout the cardiac cycle. These findings were confirmed by cardiac catheterization. We conclude that MRI is useful not only in detecting a coronary arteriovenous fistula but also in identifying its origin and the drainage site.

Adult↗
PubMed1997

Source of ATP, ADP, AMP and adenosine released from isolated rat caudal artery exposed to noradrenaline.

Purines of ATP, ADP, AMP and adenosine released from rat caudal artery with and without endothelium and the isolated smooth muscle and endothelial cells were examined, in order to determine the source. Treatment of intact segments of caudal arteries with noradrenaline (10 microM) for 3 min induced a large release of ATP, ADP, AMP and adenosine. However, if the artery segments had been denuded of their endothelial lining, noradrenraline induced only a slight release of purines. Endothelial cells in primary culture prepared from caudal arteries, when exposed to noradrenaline for 3 min released large amounts of purines, whereas vascular smooth muscle cells prepared similarly and passaged endothelial cells did not release purines upon exposure to noradrenaline. These results indicate that, of smooth muscle and endothelial cells of the vascular wall, only intact endothelial cells react to alpha-adrenoceptor stimulation by releasing adenine nucleotides and adenosine.

Adenine Nucleotides↗
PubMed1997

Current status of conducting function tests in repeated dose toxicity studies in Japan.

It seems desirable to conduct as many function tests as possible in repeated dose toxicity studies, but is it practicable? The current status of conducting function tests in repeated dose toxicity studies in Japan was investigated by a literature survey of more than one thousand papers published in seven Japanese toxicology journals during the past 10 years and by a questionnaire survey directed to toxicologists among the Japan Pharmaceutical Manufacturers Association (JPMA) member companies. The function tests often carried out in repeated dose toxicity studies were, for example: 1) electro-retinography (ERG) and visually evoked potential (VEP) for visual test and tonometer for intraocular pressure; 2) auricular reflex, evoked response audiometry (ERA) and auditory brainstem response (ABR) to sound stimuli; 3) respiration and heart rate, electrocardiogram (ECG) and blood pressure by noninvasive cuff methods or using electronic devices such as telemetry; 4) body temperature, spontaneous motility and some adaptation tests (using rotarod and sloped plate in rats); 5) indocyanin (ICG) or bromosulfophtalein (BSP) for hepatic test; 6) phenolsulfonphtalein (PSP) and creatinine clearance for renal test; and 7) immunoglobulin, leukocyte phagocytosis, lymphocyte blastgenesis and natural killer cell (NK) for immuno-reaction test. Limitations to conducting function tests in repeated dose toxicity studies and issues to be resolved were discussed, based on questions and suggestions given by the respondents to the questionnaire. Although it certainly seemed desirable to conduct as many function tests as possible in repeated dose toxicity studies, most of the function tests so far introduced into toxicity studies were not satisfactory, because those tests could not be carried out under the restricted conditions of repeated dose toxicity studies, and not much reliable data from function tests were obtainable. A variety of function tests should firstly be incorporated into single dose toxicity studies together with development of a new concept for methodology in safety pharmacology.

Animals↗
PubMed1997

Postprandial atrioventricular block in a patient with diabetes mellitus.

Postprandial atrioventricular (AV) block and hypotension occurred in an 80-year-old man with a 13-year history of diabetes mellitus. Two weeks before admission, he experienced syncope on two occasions after lunch. Master's two-step test induced second degree AV block (2:1 block). Four days after admission, syncope recurred while walking 1 hour after eating; electrocardiogram (ECG) showed complete AV block following 2:1 block. PP interval analysis suggested phase 3 block as the mechanism of AV block. Electrophysiologic study revealed 2:1 HV block. Postprandial syncope ceased after permanent pacemaker implantation. Postprandial AV block and hypotension merit close attention in diabetics.

Aged↗
PubMed1997

Use of carbon dioxide microbubble-enhanced sonographic angiography for transcatheter arterial chemoembolization of hepatocellular carcinoma.

OBJECTIVE: Our objective was to determine the usefulness of sonographic angiography with carbon dioxide microbubbles during transcatheter arterial chemoembolization for hepatocellular carcinoma. SUBJECTS AND METHODS: Thirty-four patients with hepatocellular carcinoma underwent sonographic angiography during transcatheter arterial chemoembolization. Digital subtraction angiography failed to reveal tumors in 27 patients. Tumor stain became obscure on digital subtraction angiography after the catheter was inserted into distal branches in seven patients. Sonographic angiography was performed after injection of carbon dioxide microbubbles into the hepatic artery selected for transcatheter arterial chemoembolization. RESULTS: In angiographically undetectable hepatocellular carcinomas, sonographic angiography revealed tumor vascularity in 17 patients in whom transcatheter arterial chemoembolization was then performed. For the two patients who underwent a second transcatheter arterial chemoembolization, the existence of alternative feeding vessels was confirmed by sonographic angiography. In the remaining 10 patients, tumor vascularity was not seen on sonographic angiography; percutaneous ethanol injection therapy was then performed. Sonographic angiography clearly revealed tumor vascularity in patients in whom staining became obscure on digital subtraction angiography after the catheter was inserted into a peripheral branch of the hepatic artery. In all 24 patients who underwent transcatheter arterial chemoembolization, sonographic angiography was useful for determining the artery suitable for transcatheter arterial chemoembolization and for monitoring tumor perfusion in the selected artery. CONCLUSION: Sonographic angiography can be used to determine not only the therapeutic strategy for treatment of hepatocellular carcinoma but also whether the tumor is supplied by the artery selected for transcatheter arterial chemoembolization, especially when the tumor is not revealed by digital subtraction angiography.

Aged↗
PubMed1997

Gene amplification of int-2 and erbB in human esophageal cancer: relationship to clinicopathological variables.

Gene amplification is a relatively frequent event in human malignant tumors and is believed to play an important role in tumor progression. The int-2 and erbB genes are amplified more frequently than any other genes in human esophageal cancer. In order to investigate the correlation between these two proto-oncogenes and the clinical behavior of esophageal cancer, we examined DNA amplification of int-2 and erbB and analyzed their relationship to clinicopathological variables. Genomic DNA was extracted from 21 esophageal squamous carcinomas and normal esophageal mucosa, as well as from 4 metastatic tumors. We used Southern blot analysis for detection of gene amplification. Amplification of int-2 was observed in 13 of 21 cases (62%) and in all the metastatic tumors (4/4; 100%). We found a significant correlation between amplification of int-2 and the length of the primary lesion. Amplification of erbB was detected in 3 of 18 patients (17%). All patients who showed amplification of erbB also demonstrated amplification of int-2. These results suggest that amplification of int-2 or neighboring genes on 11q may participate in tumor progression and metastasis in patients with esophageal squamous cancer.

Age Factors↗
PubMed1997

Production of the immunosuppressive cytokine interleukin-10 by Epstein-Barr-virus-expressing pyothorax-associated lymphoma: possible role in the development of overt lymphoma in immunocompetent hosts.

Malignant lymphomas frequently develop in the pleural cavity of patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most PALs are diffuse lymphomas of B cell type and contain Epstein-Barr virus (EBV) DNA. We have established two lymphoma cell lines from the biopsy specimens of PAL cases, OPL-1 and OPL-2. Both cell lines contain EBV DNA, but only OPL-1 expresses EBV nuclear antigen 2, which works as a target molecule for the cell-mediated immune response. As systemic immunodeficiency is unlikely to be present in PAL patients, PAL from which OPL-1 derived was not expected to be fully developed. In this study, we examined the expression of immunosuppressive factors in OPLs. Only OPL-1, not OPL-2, expressed interleukin-10 (IL-10) mRNA and secreted IL-10 into culture supernatant. Both OPL-1 and OPL-2 expressed transforming growth factor (TGF)-beta 1 mRNA; however, neither expressed latent TGF-beta-binding protein mRNA at a detectable level by Northern blot analysis. Because TGF-beta expresses its functions in cooperation with latent TGF-beta-binding protein, the biological functions of TGF-beta 1 could be negligible. Neither cell line expressed at a detectable level EBV BCRF-1 mRNA, a viral gene product that is partly homologous to human IL-10 and shares biological activities of IL-10. Although IL-10 is reported to promote the growth of activated or neoplastic B cells, OPL-1 did not respond to human recombinant IL-10 by growing faster. As OPL-1 expresses a target antigen for the host cytotoxic T-cell response, the production of an immuno-suppressive cytokine, IL-10, might contribute to the development of overt lymphoma by inducing locally immunosuppressive circumstances. The present study suggests that an immunosuppressive cytokine plays a role in lymphomagenesis of immunocompetent patients.

Animals↗
PubMed1997

[Brain uptake ratio as an index of cerebral blood flow obtained with 99mTc-ECD].

A new index of cerebral blood flow (brain uptake ratio, BUR) using 99mTc-ECD was developed and evaluated in 66 patients (132 cerebral hemispheres). BUR was calculated from brain count in anterior planar image (60-80 sec after injection of 99mTc-ECD) divided by the summation of the count of aortic arch during first transit of radionuclide. BUR correlated well with brain perfusion index (BPI) obtained with Patlak plot method (r = 0.960, p < 0.001). In conclusion, BUR is useful as a simple and non-invasive index reflecting cerebral blood flow.

Adolescent↗
PubMed1997

[Japanese version of the Neuropsychiatric Inventory--a scoring system for neuropsychiatric disturbance in dementia patients].

BACKGROUND AND PURPOSE: Neuropsychiatric disturbances are common and burdensome symptoms of dementias. Assessment and measurement of neuropsychiatric disturbances are indispensable to the management of patients with dementia and for clinical research. No standardized instruments have been developed for these purposes in Japan. The Neuropsychiatric Inventory (NPI), developed by Cummings et al., is a standardized, validated, and reliable tool to assess a wide range of neuropsychiatric derangements in patients with dementia, and has been used in clinical studies in North America. In this study, we prepared a Japanese version of the NPI and tested its reliability and usefulness in dementia patients. SUBJECTS AND METHODS: The subjects were 174 patients with dementia, including Alzheimer's disease (140), frontotemporal dementia (12), vascular dementia (19), and normal pressure hydrocephalus (3), whose diagnosis was made on the basis of the results of extensive examinations including MRI and PET/SPECT of the brain and appropriate clinical diagnostic criteria for each disorder. The subjects consisted of 133 women and 41 men; their mean age was 72.6 +/- 7.7 years (S.D.; range: 49 to 88) years. An examiner (neurologist) used the NPI to interview a caregiver familiar with the patient's everyday behavior. In 24 randomly selected patients interview was repeated by another examiner (psychiatrist) one month later, and test-retest reliability was evaluated. The Clinical Dementia Rating (CDR), the Mini-Mental State Examination (MMSE), and the Alzheimer's Disease Assessment Scale (ADAS) were used to assess the severity of the dementia and cognitive impairment. RESULTS: The MMSE scores ranged from 5 to 29 (mean +/- SD = 19.0 +/- 4.8) and the ADAS scores ranged from 7 to 63 (24.3 +/- 10.9). The CDR score was 0.5 in 17 patients, 1 in 95 patients, 2 in 52 patients, and 3 in 10 patient. Test-retest reliability of each score was acceptably high, and the correlation coefficient for each score obtained by repeated assessments in this study was similar to the coefficient in the original report. Apathy was the most common behavior in the ten abnormal behavioral domains, and euphoria was the least common. The prevalence of abnormal findings was also comparable to the results in the original report. The total NPI scores and many of the NPI subscale scores were significantly correlated with both the severity of dementia and cognitive impairment. CONCLUSIONS: This Japanese version of NPI, whose reliability and competency are comparable to those of the original version, is a reliable and useful tool for measuring neuropsychiatric disturbances in dementia patients.

Aged↗
PubMed1997

[Relationship between medical services utilization and preventive health behavior].

The purpose of this study was to examine the relationship between medical services utilization and preventive health behavior and to seek the factors affecting them. Subjects were 568 persons who were from 40 to 59 years old and lived in a community. Preventive health behaviors they actually performed and their interests in health were asked by questionnaire. Preventive health behaviors assessed included smoking behavior, drinking behavior, adequate hours of sleep, physical exercise, regularity of meals, and medical checkups. Medical services utilization, which included the number of visits to medical care providers, was measured by their medical claims during one year. Except for adequate hours of sleep, preventive health behaviors correlated positively with each other. A strong positive correlation was found between medical services utilization and medical checkups. However, correlations between medical services utilization and other preventive health behaviors were not statistically significant. Persons who performed preventive health behaviors and persons who utilized medical services scored higher in interest in health than persons who didn't. These results show that medical services utilization and preventive health behavior are strongly associated with interest in health, but are weakly correlated with each other.

Adult↗