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Biomedical subjects

R Horie

Publications and source records attributed to R Horie.

At least 37 records · Page 2Linked to original sources

A new cancer-associated antigen defined by a monoclonal antibody against a synthetic carbohydrate chain.

Carbohydrate antigens can be designed by referring to previously defined carbohydrate structures. We have generated a novel monoclonal antibody (MAb) (F1 alpha-75) against an artificially designed antigen (F1 alpha), using organic-synthetic chemistry methods and hybridoma technology. F1 alpha (Gal beta 1-->4GlcNAc beta 1-->6GalNAc alpha 1-->Ser/Thr) belongs to core type 6 of O-linked glycans, which has not been previously reported in human cancers. To produce antibodies against F1 alpha, a glycolipid was synthesized which carries the carbohydrate portion of F1 alpha on a ceramide foundation (Gal beta 1-->4GlcNAc beta 1-->6GalNAc alpha 1-->Cer). The MAbs we obtained (F1 alpha-75, F1 alpha-87) specifically recognized F1 alpha and had only a very weak or no cross-reactivity with other glycolipids similar to F1 alpha. We investigated the expression of F1 alpha in human tissues, including 110 gastric cancers, 73 colon cancers and 42 pancreatic cancers. F1 alpha was found in human cancerous tissues but not in normal adult tissues. The rate of positive staining with F1 alpha-75 was 80.0% for gastric cancer, 52.4% for pancreatic cancer and 38.4% for colon cancer. F1 alpha-75 also reacted with the tissues neighboring gastric and pancreatic tumors but not intensely. Among fetal tissues, F1 alpha-75 reacted with the pyloric glands of the stomach, the centro-acinar cells of the pancreas, the convoluted tubules of the kidney and the terminal bronchioles of the lung.

Antibodies, Monoclonal↗

Community-based prevention of stroke: nutritional improvement in Japan.

OBJECTIVES: (1) To demonstrate the importance of nutrition, especially sodium restriction and increased potassium and protein intakes, in the prevention of hypertension and stroke in a pilot study involving senior citizens. (2) To design a population-based intervention in the Shimane Prefecture of Japan concerning dietary factors such as low sodium and high potassium, protein, magnesium, calcium and dietary fibre in the prevention of stroke. DESIGN AND METHODS: The intervention study was carried out at a senior citizens' residence and included general health education along with a reduction of dietary salt intake and increases in vegetable and protein, especially from seafood. Sixty-three healthy senior citizens (average age: 74.8 +/- 7.7 years) had their daily meals modified to a low sodium/potassium ratio for four weeks without their knowledge by the use of a potassium chloride substitute for salt, soy sauce and bean paste, which contains much less sodium and more potassium. Monosodium L-glutamate monohydrate used for cooking was changed to monopotassium L-glutamate monohydrate. Blood pressure was measured with the patient in the sitting position. Daily dietary sodium and potassium intakes were assessed by flame photometry from 24-hour urine specimens. Extensive intervention programs were introduced into the Shimane Prefecture, which has a population of 750,000, through health education classes for housewives, home visits by health nurses and an educational TV program for dietary improvement. The mortality from stroke was monitored for 10 years and compared with the average in Japan. RESULTS: The blood pressure lowering effect of reducing the dietary sodium/potassium ratio was confirmed through a pilot intervention study at the senior citizens' residence. The mortality rates for stroke in the middle-aged population from the Shimane Prefecture during the 10 years after the introduction of dietary improvement had a steeper decline in hemorrhagic, ischemic and all strokes than the average for Japan.

Adult↗

Nutritional factors for stroke and major cardiovascular diseases: international epidemiological comparison of dietary prevention.

OBJECTIVE: To assess the relationship of biological markers of dietary factors with blood pressure (BP) (Core Study) and with age-adjusted mortality rates of stroke and ischemic heart disease (Complete Study) in the WHO Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study, a multicentre epidemiological study in 55 centres of 24 countries as of 1993. DESIGN AND METHODS: From each population, 100 men and 100 women aged 48 to 56 years were randomly selected for BP measurement, 24-hour urine collection, blood tests, etc. Various biological dietary markers from the urine and blood were analysed centrally. Age-adjusted mortality rates from stroke and ischemic heart disease were obtained from 19 centres in 14 countries. RESULTS: Core Study: Cross-centre analyses, using simple linear regression, showed a positive relationship of body mass index to systolic BP and diastolic BP in men (p < 0.001) and women (p < 0.05). There were also strong positive correlations between 24-hour sodium excretion rates and both systolic and diastolic BP (both p < 0.01) in men. An inverse relationship was found between the 24-hour magnesium/creatinine excretion ratio and diastolic BP (p < 0.05) in men. Complete Study: Stroke mortality was significantly positively related to the 24-hour sodium excretion rate in men (p < 0.01) and to the sodium/potassium ratio in both sexes (p < 0.05). It showed an inverse relationship of serum phospholipid with serum total cholesterol (p < 0.05) and a positive relationship with arachidonic acid. A strong positive relationship between serum cholesterol level and ischemic heart disease (p < 0.001) was observed in men. The serum phospholipid n-3 polyunsaturated fatty acid (PUFA) level and the PUFA to saturated fatty acid (SFA) ratio were significantly inversely correlated with ischemic heart disease. The 24-hour taurine excretion rate, a biological marker of seafood protein intake, showed a significant inverse correlation with ischemic heart disease in both sexes (p < 0.01). CONCLUSION: The Core Study revealed a consistent adverse effect of high body mass index and excess salt intake on BP and a beneficial effect of magnesium on BP. The Complete Study demonstrated an adverse effect of high sodium, low potassium intake and hypercholesterolemia on stroke; and an adverse effect of cholesterolemia as well as beneficial effects of serum phospholipid n-3 PUFA, PUFA/SFA and the taurine excretion rate on death from ischemic heart disease.

Arachidonic Acids↗

High expression of the CD30 molecule in human decidual cells.

CD30 is a receptor-type membrane protein that belongs to the nerve growth receptor superfamily. It is expressed on Hodgkin's cells and activated lymphocytes, as well as in some human malignancies including malignant lymphomas, embryonal carcinomas, and other mesenchymal tumors. However, whether it is expressed in normal tissues remains unclear. To study the expression and biological function of CD30, we first examined various human tissues by immunohistochemistry. The monoclonal antibody Ber-H2 intensely stained the membranes of decidual and endometrial cells with decidual change in frozen sections. Western blots of these tissues with Ber-H2 revealed bands of 120, 105, and 90 kd as found on CD30-expressing cells. Northern blots of these tissues using a CD30 cDNA probe detected mRNAs of the same molecular mass and variety as those in the positive control cell line HUT 102. These results indicated that CD30 is expressed in human endometrial tissue with decidual change and imply that CD30 expression in endometrial tissue is induced by hormonal control.

Base Sequence↗

Cerebrovascular protection by sequential bilateral carotid artery ligation in aged spontaneously hypertensive rats.

1. Sequential bilateral carotid artery ligation (BCL) separated by a 1 week interval was performed on 5 month spontaneously hypertensive rats (SHR) (i.e. SHRSR-B1/Izm) and the developmental course of hypertension and cerebrovascular lesions in advanced age were analysed as compared with those in age-matched sham-operated controls. 2. Behavioural activity and behavioural reaction to light were also investigated in the above-mentioned SHR, young and adult stroke-prone SHR (i.e. SHRSP-A3/Izm), SHR (i.e. B1/Izm) and Wistar-Kyoto rats (i.e. WKY/Izm). 3. All of the control SHR developed severe hypertension resulting in cerebral stroke with focal oedema due to cerebral haemorrhage and infarction as a result of arterionecrosis 18 months after birth. 4. SHR usually die within a few days of BCL. In the present study, however, they successfully survived without cerebrovascular damage for a long time, although they developed a similar severe hypertension in a significantly shorter period of time (P < 0.05) and showed behavioural abnormalities that were probably due to severe cerebral ischaemia. 5. These experimental results suggest an ischaemic tolerance phenomenon in a hypertensive model that was exposed to mild ischaemic stress by unilateral carotid artery ligation (UCL) before the subsequent induction of severe ischaemia by BCL. The results also suggest that an aggravation of hypertensive cerebrovascular changes due to long-lasting ischaemia after BCL was prevented through a possible cumulative effect of ischaemic stress.

Aging↗

Intralymphocytic free calcium and magnesium in stroke-prone spontaneously hypertensive rats and effects of blood pressure and various antihypertensive agents.

1. Free Ca2+ ([Ca2+]i) and Mg2+ ([Mg2+]i) were measured in peripheral lymphocytes from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) at the age of 5, 7 and 17 weeks, from various antihypertensive agents-treated SHRSP, and from secondary hypertensive WKY. 2. At the age of 5 weeks, no difference was observed in systolic blood pressure (SBP), or lymphocyte [Ca2+]i and [Mg2+]i between SHRSP and WKY. At the age of 7 or 17 weeks, SBP and [Ca2+]i of SHRSP were significantly higher than in WKY, and at the age of 17 weeks, [Mg2+]i of SHRSP was significantly lower than in WKY. Further, [Ca2+]i or [Mg2+]i was positively or negatively correlated to SBP, and [Mg2+]i was negatively correlated to [Ca2+]i. 3. SBP of SHRSP fell significantly after antihypertensive treatment with calcium antagonist, angiotensin-converting enzyme (ACE) inhibitor or hydralazine for 40 days. [Ca2+]i was significantly lower in calcium antagonist and hydralazine groups, and tended to be low in ACE inhibitor group. These four groups showed no difference in [Mg2+]i. 4. After 40-day administration of NG-nitro-L-arginine (L-NNA), WKY developed severe hypertension, but there were no significant differences in lymphocyte [Ca2+]i and [Mg2+]i between the L-NNA treated and non-treated groups. 5. These results suggested that increased lymphocyte [Ca2+]i and decreased [Mg2+]i observed in SHRSP are not only secondary to hypertension but possibly related to a basic genetic abnormality of divalent cation handling.

Animals↗

Comparative study of various genetic hypertensive rat strains: blood pressure, body weight, growth and organ weights.

In an attempt to compare various genetic strains of hypertensive rats, representative hypertensive strains and associated controls (male, 1-month-old, 6-10 of each strain and 18 strains in total) were collected at a single center (National Institutes of Health; NIH, United States), maintained under the same experimental conditions with normal sodium NIH open formula diet and studied by a single investigator using standard techniques. Animals were measured for blood pressure (BP) by a tail-cuff method without anesthesia and body weight (BW) at 10 and 12 weeks of age and killed to measure organ weights. Hypertension was severe (> 190 mmHg) in spontaneously hypertensive rats (SHR) and their stroke-prone substrains at 12 weeks of age but mild to moderate (145-160 mmHg) in the rest of the hypertensive strains (Dahl's, Milan, Lyon, Sabra, and New Zealand Strains). Regarding organ size, partial correlation analysis showed that organ weights, except for brain and adrenal glands, are good functions of BW and that weight of the left ventricle (LV) was the only one significantly linked to BP levels. A bivariate regression model for LV weight was obtained as follows: LV(mg) = 1.478 BW(g) + 2.13BP(mmHg) - 51(R = 0.878, P < 0.001). The presence of some genetic factor regulating relative organ size independently of BW and BP was suggested in LV weight as well as in the weight of the other organs. Among the strains, MHS was found to be unique for the smallest kidney size and New Zealand strains for the greatest relative LV size when adjusted to allow for the influence of BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Potassium accelerates urinary sodium excretion during salt loading without stimulating atrial natriuretic polypeptide secretion.

1. Effects of potassium (K) supplementation (100 mEq/day) on urinary sodium (Na) excretion and on the secretion of atrial natriuretic polypeptide (ANP) during salt loading (350 mEq/day) were studied in 12 healthy salt-resistant normotensives under strictly controlled metabolic ward conditions. 2. Urinary volume and Na excretion on the first day of the high salt period (HSP) were significantly greater in the K-supplemented group (KG) than in the control group (CG). 3. There was a significant gain in bodyweight after salt loading in both groups, with a significantly greater gain in CG on the second day of HSP. Haematocrit decreased significantly during salt loading in both groups, the degree of which was significantly greater in CG. 4. Plasma norepinephrine decreased significantly during salt loading in both groups, the degree of which was significantly less in KG than in CG. A significant increase in plasma ANP was observed in CG on and after the second day of HSP, while a significant increase in plasma ANP was observed on the fifth day of HSP in KG. 5. These findings indicate that K supplementation accelerates diuresis and natriuresis, resulting in moderate suppression of volume expansion induced by salt loading and that this accelerated diuresis and natriuresis is not a result of the action of ANP.

Adult↗

International cooperative study on the relationship between dietary factors and blood pressure: a preliminary report from the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. The CARDIAC Cooperative Study Research Group.

1. To investigate the epidemiological relationship of dietary factors to blood pressure (BP) and major cardiovascular diseases, we carried out the international cooperative Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study, which so far involves 48 centers in 20 countries as of August 1991. From each population, 100 men and 100 women aged 50-54 years were randomly selected for BP measurement, 24-h urine collection, blood tests, and medical interview. Various biological markers of diets from urine and blood were analyzed centrally in the Izumo CARDIAC center. 2. Cross center analysis using simple linear regression revealed strong significant correlations of body mass index (BMI) to systolic BP (SBP; p < 0.01) and diastolic BP (DBP; p < 0.001) in men. 24-h urinary sodium (Na) excretion in men also showed significant correlations with SBP (p < 0.05) and DBP p < 0.05) even after controlling for the effect of BMI (SBP; p < 0.05, DBP; p < 0.05). 3. Within center analysis using multiple linear regression implied that BMI and Na strongly adversely affect BP, whereas magnesium may have beneficial influence on BP. 4. Multicolinearities among 24h urinary sodium, calcium, and urea nitrogen were noted in men.

Body Mass Index↗

Gene-environment interaction in hypertension, stroke and atherosclerosis in experimental models and supportive findings from a world-wide cross-sectional epidemiological survey: a WHO-cardiac study.

1. Genetic rat models of hypertension, such as spontaneously hypertensive rats (SHR) and in particular, stroke-prone SHR (SHRSP) are useful models for research on the genetic pathogenesis, gene-environment interaction and control of environmental factors for the prevention of hypertension and related cardiovascular diseases (CVD). 2. Since recent genetic analysis of hypertension in SHRSP indicated that one of the hypertensive genes related to salt-induced blood pressure (BP) rise was linked with the gene of the angiotensin-converting enzyme, gene-environment interaction is important in the humoral, neural, vascular and nutritional mechanisms of hypertension and CVD. 3. Extensive experimental studies in SHRSP by the authors have demonstrated nutritional factors counteracting directly or indirectly against the adverse effect of excess salt intake, such as K, Mg, Ca, dietary fibres, protein, some amino acids and fatty acids, etc.; they are therefore effective in preventing stroke, the typical complication of hypertension. 4. Experimental atherosclerotic models were established in SHRSP, which indicated also a gene-environment interaction in the pathogenesis of atherosclerosis at the cellular level of vascular smooth muscle cells. Excess salt intake accelerated cholesterol absorption from the intestine to induce arterial fat deposition as well as to active platelet aggregation by the mechanism of increased intracellular Ca2+ mobilization. 5. Based on such experimental findings on the hypertension and related CVD prevention, a cross-sectional multicentre epidemiological 'CVD and Alimentary Comparison' Study (WHO-CARDIAC Study) was designed to assess the relationship of biological markers of dietary factors with BP ('core' study) and major CVD mortalities ('complete' study) and has been successfully undertaken for the past 8 years in co-operation with 54 centres in 23 countries. 6. The results of 'core' study so far obtained by cross-centre simple linear regression analysis demonstrated adverse effects of body mass index and salt intake on BP in men and possible beneficial effects of Mg by within-centre multiple linear regression analysis. 7. Preliminary cross-centre simple linear regression analysis of the 'complete' study indicated a positive correlation of serum cholesterol levels and negative correlation of serum phospholipid poly-unsaturated to unsaturated fatty acid ratios and 24 h urinary taurine excretion with coronary heart diseases mortality; a positive correlation of 24 h urinary Na and Na/K ratios and a negative correlation of serum cholesterol levels with stroke mortalities was indicated. 8. These epidemiological data confirmed mostly the applicability of experimental findings to the nutritional prevention of hypertension and CVD prevention.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Stroke-prone SHR (SHRSP) as a model for osteoporosis.

Since previous studies on SHRSP showed various abnormalities in Ca metabolism, aged SHRSP together with age-matched Wistar-Kyoto (WKY) were examined for bone mineral density and contents as well as bone histomorphometry and mechanical properties. SHRSP and WKY, 10 rats of each group at the age of 7 to 8 months were sacrificed with or without tetracycline and calcein labellings for the estimation of mineral appositional rate. Both femurs, tibia and the 1st lumbar vertebra were extirpated from each rat; one femur was used for mineral density and content analyses and the other was used for analyzing mechanical properties by three point-bending and torque methods (Maruto, MZ500D). Mineral density and cortical thickness index were decreased significantly in SHRSP compared with WKY, and Ca contents were decreased as well. Correspondingly femurs from SHRSP were proven to be fragile in the maximum bending stress. Undecalcified histological sections of tibial proximal epiphysis histomorphometrically indicated bone volume and trabecular thickness were significantly decreased in SHRSP. These findings together with others indicate SHRSP can be a good model for spontaneous osteoporosis in man.

Animals↗

Aggravating effects of isolated caging on the development of hypertension and its complications in stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY).

Stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) were maintained in isolation or in group to analyze the effect of isolation, one type of emotional stress, on the development of hypertension and its complications. SHRSP kept isolated during the whole or a half of the experimental period developed severer hypertension within a shorter period than those kept together with other animals throughout the experiment, and showed significantly higher incidences of cerebral stroke (40 or 33%) than the latter (8.3%). Histological and pathophysiological studies revealed pituitary-adrenal and cardiac hypertrophy accompanying more accelerated urinary epinephrine (E) excretion which indicated emotional stress caused by isolation might aggravate pathological lesions in hypertension. Neither WKY in isolation nor in groups developed hypertension, although isolated WKY had significantly heavier pituitary and adrenal glands accompanied with more accelerated urinary E and calcium excretions than WKY kept in groups.

Animals↗

Effects of long-term cerebral ischemia caused by bilateral carotid artery ligation on the acceleration or the development of hypertension in spontaneously hypertensive rats (SHR) or Wistar-Kyoto rats (WKY).

Bilateral carotid artery ligation (BCL) was performed with one week interval between the each operation in male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) aged 4 months. BP rose immediately after unilateral carotid artery ligation (UCL) and BCL in both WKY and SHR due to carotid sinus reflex. Once returning to preoperative levels after both UCL and BCL, BP of SHR and WKY increased again gradually one and 4 months after BCL and thereafter, respectively. BP was significantly higher than that in the controls of each strain, and the BP increment was significantly greater in SHR than in WKY. A significant regional cerebral blood flow (rCBF) increase on the contralateral side of carotid ligation was observed in SHR in contrast to a little change in that of WKY and a reduction of rCBF after BCL was significantly greater in SHR than in WKY. Behavioral activities in SHR were also reduced after BCL. Cerebral edema with nerve cells damage was recognized in SHR. In contrast, little change was found in WKY. On the other hand, upper cervical sympathectomy attenuated convulsive seizures after BCL more markedly in SHR, which survived longer than non-denervated SHR. These results suggest that chronic mild cerebral ischemia caused by BCL with one week interval accelerates the development of severe hypertension in SHR and developed mild hypertension in WKY. Sympathetic innervation might play much more important role in collateral circulation through the vertebrobasilar system in SHR.

Animals↗

[Acute leukemia successfully treated with natural interferon-alpha].

Natural interferon-alpha (IFN-alpha) alone was administered to a 42-year-old man with acute leukemia, whose bone marrow revealed hypocellularity (NCC = 6 X 10(4)/microliters) and a 50% increase in blasts. Initial chemotherapy regimens, including BHAC-DMP or low dose Ara-C were ineffective. One month after starting nIFN-alpha therapy, the blasts in his bone marrow decreased below 3% and peripheral blood cell counts became normal. He has been in remission for at least 7 months.

Acute Disease↗

Relative frequencies of dementia of the Alzheimer type and vascular dementia in Japanese nursing homes.

We have studied neuropathologically 200 aged nursing home residents (101 men and 99 women) autopsied between 1976 and 1985. Seventy-three of the 200 showed dementia during life, that is, 27% and 55% of the residents in nursing homes and special nursing homes, respectively. The relative frequencies of SDAT and VD in nursing homes as a whole were the same (34%). The relative frequencies of SDAT and VD in special nursing homes, where usually high concentrations of VD have been noted, were 21% and 52%, respectively. A comparison of the results of our special nursing homes (SDAT:VD = 1:2.5) and nursing homes as a whole (SDAT:VD = 1:1) with those of Barnes and Raskind (SDAT:VD = 2:1) and Rovner et al. (SDAT:VD = 3:1) showed that the frequencies of VD in Japanese nursing homes are considerably higher than those in their American counterparts.

Aged↗