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Biomedical subjects

H Sakamoto

Publications and source records attributed to H Sakamoto.

At least 271 records · Page 15Linked to original sources

Prevention of N-methylnitrosourea-induced colon carcinogenesis in F344 rats by lycopene and tomato juice rich in lycopene.

Epidemiological studies have suggested a protective effect of lycopene and lycopene-rich tomatoes against various cancers. Here, the inhibition of colon carcinogenesis by lycopene and tomato juice was investigated. Seven-week-old female F344/NSlc rats received an intrarectal dose of 2 mg (experiment I) or 4 mg (experiment II) of N-methylnitrosourea 3 times a week for 3 weeks, and had free access to one of 4 drinking fluids: plain water (control group), 17 ppm lycopene water solution (Ly group), and diluted tomato juice containing 17 ppm (Tj group) or 3.4 ppm (tj group) lycopene, throughout the experiments. The colon cancer incidence at week 35 was significantly lower in the Tj group, but not in the Ly group, than in the control group: 21% and 33% vs. 54%, in experiment I (24 rats in each group). It was significantly lower in the Tj group than in the tj and control groups, 40% vs. 72% and 84%, in experiment II (25 rats in each group). An appreciable amount of lycopene (0.02 microgram/g) was detected in the colon mucosa of rats in the Tj group, but not in the tj group. The results suggest that tomato juice rich in lycopene may have a protective effect against colon carcinogenesis.

Animals↗

Blood-brain barrier damage in reperfusion following ischemia in the hippocampus of the Mongolian gerbil brain.

Vascular permeability to intravenously injected horseradish peroxidase (HRP) was qualitatively examined in the hippocampus of ischemic Mongolian gerbil brains by light and electron microscopy. After 30 min of right common carotid artery occlusion followed by 90 min of reperfusion, the animal was perfused with a fixative and killed. Before the perfusion of the fixative, HRP was injected into the femoral vein. HRP was visualized with tetramethyl benzidine (TMB) and diamino-benzidine (DAB) for light and electron microscopy, respectively. Staining reaction with TMB for HRP appeared in medial or dorsal portions of the operated side of the hippocampus, especially around some vessels along the hippocampal fissure. Ultrastructural examination in the vessels along hippocampal fissure revealed that the endothelial cytoplasm contained HRP-filled vesicles or vacuoles in close proximity to the basal lamina, and seemed to be slightly electron-dense. Swollen pericytes, swollen astrocytic foot processes and perivascular cells with HRP-filled cytoplasm were also observed in that area. In this study, it was clearly demonstrated that intravascular macromolecules leaked transendothelially, through vessel walls in the hippocampal fissure, from the blood stream in the medial portions of the hippocampus during reperfusion following ischemia. These findings suggest that the blood-brain barrier in some vessels along the hippocampal fissure in the medial parts of the hippocampus is more vulnerable to ischemic insults than those in other brain areas.

Animals↗

Substitution of an alanine residue for glycine 146 in TMP kinase from Escherichia coli is responsible for bacterial hypersensitivity to bromodeoxyuridine.

The wild-type TMP kinases from Escherichia coli and from a strain hypersensitive to 5-bromo-2'-deoxyuridine were characterized comparatively. The mutation at codon 146 causes the substitution of an alanine residue for glycine in the enzyme, which is accompanied by changes in the relative affinities for 5-Br-UMP and TMP compared to those of the wild-type TMP kinase. Plasmids carrying the wild-type tmk gene from Escherichia coli or Bacillus subtilis, but not the defective tmk gene, restored the resistance to bromodeoxyuridine of an E. coli mutant strain.

Alanine↗

Antagonism of ANG II type 1 receptors protects the endothelium during the early stages of renal hypertension in rats.

The degree of involvement of the renin-angiotensin system in endothelial dysfunction was investigated by using a one-kidney, one-clip (1K,1C) model of renal hypertension. Male Wistar rats received 0.02% enalapril, 0.02% losartan, or tap water for 1 day before and for 48 h after the induction of renal artery stenosis or sham operation. The aorta of 1K,1C rats showed increased contraction and decreased relaxation responses produced by norepinephrine and acetylcholine, respectively, vs. control responses. Exposure to 10(-5) mol/l NG-monomethyl-L-arginine acetate augmented the contractile responses to norepinephrine to a greater extent in control rats than in the 1K,1C rats. The increased contraction and decreased relaxation responses to these agonists in the 1K,1C rats were normalized by enalapril or losartan. The addition of HOE-140 to the bath did not alter these normalized responses. Results suggest that angiotensin II causes endothelial dysfunction and reduces nitric oxide levels in 1K,1C rats. Such endothelial dysfunction enhanced the norepinephrine-induced contraction during the early-stage hypertension in 1K,1C rats.

Acetylcholine↗

Bronchial hyperresponsiveness, hypersensitivity to analgesics and urinary leukotriene E4 excretion in patients with aspirin-intolerant asthma.

This study was designed to investigate the protective effect of cromolyn sodium on airway sensitivity to sulpyrine, and bronchial responsiveness to methacholine, and to investigate whether this protective activity is associated with reduction in aspirin-induced excretion of urinary leukotriene E4 (u-LTE4), a marker of the cysteinyl LT overproduction that participates in the pathogenesis of aspirin-induced asthma. We assessed the effects of pretreatment with cromolyn sodium on bronchoconstriction precipitated by inhalation of methacholine and sulpyrine in 16 adult patients with mild or moderate aspirin-intolerant asthma; those who were in stable clinical condition and were hypersensitive to a sulpyrine provocation test were included in this study. A double-blind, randomized, crossover design was used. u-LTE4 was measured using combined reverse-phase high-performance liquid chromatography enzyme immunoassay. Cromolyn sodium protected against analgesic-induced bronchoconstriction through mechanisms that are not related to its bronchodilator property, but to the improvement of both bronchial hyperresponsiveness and hypersensitivity to analgesics (p<0.01 and p<0.001). Although excretion of u-LTE4 did not increase after the methacholine provocation test, it significantly increased after sulpyrine provocation (p<0.01). Furthermore, after pretreatment with cromolyn sodium, the maximum level of u-LTE4 after the sulpyrine provocation test was significantly lower than in controls (p<0.01). These results support the hypothesis that cysteinyl LT is one of the most important components in the pathogenesis of aspirin-intolerant asthma. Cromolyn sodium improves both hypersensitivity to analgesics, and bronchial hyperresponsiveness in aspirin-intolerant asthma.

Adult↗

Hepatic infarction caused by an embolus from an atherosclerotic lesion--a case report.

Although it has been reported that emboli from atherosclerotic disease may be more frequent than commonly appreciated, hepatic infarction caused by an arterial embolus is an unusual but serious complication. The authors describe a patient who had a secondary liver infarct during anticoagulant treatment for cerebral infarction. The thrombus causing the liver infarction was detected as a low echoic mass by transesophageal echocardiography at the right coronary sinus.

Aged↗

ET(A) receptor antagonist ameliorates nephrosclerosis and left ventricular hypertrophy induced in rat by prolonged inhibition of nitric oxide synthesis.

We investigated the ability of the ETA receptor antagonist T-0115 and the angiotensin-converting enzyme (ACE) inhibitor imidapril hydrochloride to prevent hypertensive complications induced in rats by chronic inhibition of nitric oxide (NO). Male Wistar rats were given distilled water (control), NG-nitro-L-arginine methyl ester (L-NAME) 500 mg/l, or L-NAME plus imidapril 10 mg/l in the drinking water. In rats treated with L-NAME 500 mg/l plus T-0115, T-0115 was given in the food at a dose of 0.2 mg/g food or 0.6 mg/g food. We then collected 24-h urine samples at 2, 4, and 6 wk, obtained blood samples at 6 wk, and histologically examined the kidney and heart. L-NAME markedly reduced the levels of NO metabolites in serum and urine while increasing the tail-cuff blood pressure, the urinary albumin level (1.90+/-0.65 vs. 0.05+/-0.02 mg/d/100 g in control), and the area of the left ventricular wall (83.3+/-3.0 vs. 69.8+/-1.8 mm2 in control). The plasma renin activity was significantly higher in rats treated with L-NAME than in the control rats. The concomitant administration of T-0115 0.6 mg/g food with L-NAME ameliorated the tail-cuff pressure and the albuminuria (0.56+/-0.23 mg/d/100 g), although to a lesser extent than the changes seen with imidapril 10 mg/l. T-0115 0.6 mg/g food prevented left ventricular hypertrophy as effectively as imidapril 10 mg/l (70.8+/-1.8 with T-0115 vs. 68.3+/-2.7 mm2 with imidapril). Chronic inhibition of NO synthesis produced left ventricular hypertrophy and nephrosclerosis. Our results demonstrate that inhibition of the renin-angiotensin system morely effectively prevents nephrosclerosis than does the blockade of ETA receptors in a model of hypertension induced by chronic NO blockade. However, inhibition of the ET-1 pathway appeared to be as effective as ACE inhibitors in preventing left ventricular hypertrophy in this model.

Albuminuria↗

Circulatory arrest under hypothermic anesthesia using abdominal cavity cooling.

The purpose of this study was to investigate the potential for circulatory arrest during surgery under systemic hypothermic anesthesia, using the abdominal cavity cooling method. Eighteen beagles, each weighing 10.5 +/- 2.3 kg, were cooled by filling the abdominal cavity with crushed ice. Just after the esophageal temperature reached 30 degrees C, the heart was exposed, and a left-heart bypass from the left atrium to the aortic root was created. At 20-23 degrees C, the heart was arrested by infusing cooled Young's solution into the aortic root. After a period of cardiac arrest, resuscitation and rewarming were initiated simultaneously. Throughout these procedures, an electrocardiogram (ECG) and the arterial blood pressure (ABP) were monitored continuously. Hematocrit (Ht), total protein (TP), and arterial blood pH and gases were measured every 30 min. The recoveries after surgery were divided into three types as follows, 1) recovery without any complications-11 dogs, 2) not extubated with spontaneous breathing-4 dogs, 3) no reappearance of heart beat-3 dogs. PaO2 during resuscitation was significantly higher in dogs which recovered completely than in the rest of the dogs. These results suggest that hypothermia induced by the abdominal cavity cooling method could be useful for organ-protection during open-heart surgery, and that successful recovery may be attained through protection of the lung as well as the myocardium.

Abdomen↗

Electroejaculation and semen characteristics of the captive Hokkaido brown bear (Ursus arctos yesoensis).

An electroejaculation technique was applied to the Hokkaido brown bear (Ursus arctos yesoensis) for semen collection and characterization of their seminal traits. Ten captive sexually mature bears were anesthetized and subjected to 21 electroejaculation trials during their mating season in 1995 and 1996. Spermic electroejaculates were recovered from 6 of the 10 bears (14 of 21 trials). The semen was characterized by serous fluid of semitransparent white color and a neutral pH. The mean values of ejaculate volume, sperm concentration, percentage of sperm motility, percentage of live spermatozoa, and percentage of pleiomorphic forms were 2.7 ml, 471.6 x 10(6) cells/ml, 80.2%, 89.7% and 21.8%, respectively. Although there was considerable variation among the seminal traits of the individual bears, the electroejaculation technique was effective in obtaining ejaculates from captive bears.

Animals↗

Age-related changes in blood coagulation and fibrinolysis in mice fed on a high-cholesterol diet.

To investigate the pathogenesis of hyperlipidemia-induced atherosclerosis, we examined age-dependent changes in platelet activity, blood coagulation and fibrinolysis in susceptibility to a high cholesterol diet (HCD) feeding in male ICR mice. Pretreatment of platelet-rich-plasma from HCD feeding mice for 3 days with epinephrine (300 microM) resulted in a marked enhancement of adenosine 5'-diphosphate (ADP: 0.1 microM) or collagen (0.7 microgram/ml)-stimulated aggregation compared with the same in control mice. Yohimbine as alpha 2-adrenergic blocker antagonized these aggregations in a dose-dependent manner. A significant increase in plasma total cholesterol and VLDL (very low-density lipoprotein)-LDL (low-density lipoprotein)-cholesterol and the liver/body weight ratio was observed in mice fed on HCD for 3 months (3-month HCD mice). In the early phase of this experiment, a significant increase in fibrinogen was observed. In the middle phase, increases in the activity of antithrombin III (ATIII) and alpha 2-plasmin inhibitor (alpha 2-Pl) followed. Plasminogen content gradually decreased in both normal diet and HCD mice throughout the experiment. The activity of plasminogen activator inhibitor (PAI) decreased in 3-month HCD mice. Morphological observation of the aortic arch from 3-month HCD mice revealed apparent atheromatous plaques not seen in control mice. These results suggest that 3-month HCD mice can be a convenient hyperlipidemia-induced atherosclerotic model and the changes in platelet activity, coagulation and fibrinolysis in the early phase may be a cause of pathologic changes in this model.

Aging↗

Mutations in CLCN5 chloride channel in Japanese patients with low molecular weight proteinuria.

Mutations in the CLCN5 gene have been demonstrated in three disorders of hypercalciuric nephrolithiasis, i.e., Dent's disease, X-linked recessive nephrolithiasis, and X-linked recessive hypophosphatemic rickets. Recently, a number of Japanese children with low molecular weight proteinuria (LMWP) showing symptoms similar to those shown by patients with Dent's disease in British families have also been reported to have mutations in the CLCN5 gene. The present study examines five unrelated Japanese families with LMWP, two of which lacked any signs other than LMWP, and three of which had several signs other than LMWP, i.e., hypercalciuria, aminoaciduria, hypophosphatemia, and rickets. One nonsense (E118X) and one missense (W22G) mutation were found in three patients in the two families having only LMWP. One genomic deletion including exons 5 to 8 in the CLCN5 gene was found in a patient with hypophosphatemic rickets, and a nonsense mutation (R347X) was found in one patient with LMWP and slight hypercalciuria. No mutations of the exons and exon-intron boundaries in the CLCN5 gene were found in one patient with LMWP, aminoaciduria, and hypokalemia. In addition to the predicted loss of chloride channel function in these nonsense and deletion mutations, the loss of function in the missense mutation W22G was confirmed in the Xenopus oocyte expression system. These results clarified four novel mutations in the CLCN5 genes, and additionally suggested that the loss-of-function mutation of the CLCN5 does not necessarily lead to hypercalciuria and nephrocalcinosis in the early stage of the disease, and that LMWP is an early and essential manifestation of disorders of the CLC-5 chloride channel.

Adult↗

Cerebellar mutism after basilar artery occlusion--case report.

A 30-year-old female became comatose due to embolic occlusion of the basilar artery, caused by surgical injury to the origin of the vertebral artery during removal of a neurinoma in the upper thoracic paravertebral region. The basilar artery occlusion was treated by local fibrinolysis through a microcatheter. Two weeks later she recovered her consciousness but suffered mutism. Her speech disturbance was characterized by severe ataxic dysarthria known as "cerebellar mutism" but without cranial nerve paresis. The mutism gradually improved during the following 3 months. This is case of cerebellar mutism was apparently due to ischemic stroke. Disturbance by hypoperfusion of the cerebellum and brain stem may have been involved in the pathogenesis of cerebellar mutism.

Adult↗

Rupture mechanism of a thrombosed slow-growing giant aneurysm of the vertebral artery--case report.

A 76-year-old male developed left hemiparesis in July 1991. The diagnosis was thrombosed giant vertebral artery aneurysm. He showed progressive symptoms and signs of brainstem compression, but refused surgery and was followed up without treatment. He died of rupture of the aneurysm and underwent autopsy in March 1995. Histological examination of the aneurysm revealed fresh clot in the aneurysmal lumen, old thrombus surrounding the aneurysmal lumen, and more recent hemorrhage between the old thrombus and the inner aneurysmal wall. The most important histological feature was the many clefts containing fresh blood clots in the old thrombus near the wall of the distal neck. These clefts were not lined with endothelial cells, and seemed to connect the lumen of the parent artery with the most peripheral fresh hemorrhage. However, the diameter of each of these clefts is apparently not large enough to transmit the blood pressure of the parent artery. Simple dissection of the aneurysmal wall by blood flow in the lumen through many clefts in the old thrombus of the distal neck may be involved in the growth and rupture of thrombosed giant aneurysms of the vertebral artery.

Aged↗

[A case of Sjögren's syndrome associated with inflammatory pseudotumor of the liver].

A 71-year-old man had noticed a dry sensation in the mouth with swelling of bilateral parotid glands in 1988. He was given a diagnosis of Sjögren's syndrome (SS) on the basis of characteristic findings of sialography and a minor salivary gland biopsy. He was admitted to our department in Febuary 1995 because of general fatigue of 2 month's duration. Laboratory data showed both positive anti-SSA and anti-SSB antibodies, liver dysfunction, hypoalbuminemia, and thrombocytopenia. Abdominal CT and MRI demonstrated a 2-cm intrahepatic mass (S 6) with enhanced areas at the periphery. The liver biopsy yielded fragments from the intrahepatic mass and hepatic parenchyma. The former was composed of plasma cells, lymphocytes, and histiocytes, compatible with the diagnosis of inflammatory pseudotumor of the liver. The pathological diagnosis of the latter specimen was primary biliary cirrhosis, although antimitochondrial antibody was negative. The intrahepatic mass gradually decreased in size without treatment. Inflammatory pseudotumor is considered to be a benign inflammatory condition simulating a neoplasma and the possibility of an autoimmune reaction is suggested on the basis of etiology. This is the first report of an inflammatory pseudotumor associated with Sjögren's syndrome developing in the liver. The inflammatory pseudotumor should be considered as a possible diagnosis in cases where the tumor is embedded in the liver.

Aged↗

Study of standard tablet formulation based on fluidized-bed granulation.

In this study, acetaminophen, ascorbic acid, and ethenzamide were selected as model drugs for tableting granules. Agitation and fluidized-bed granulation were carried out at three drug contents of 30, 50, and 70%. Compared with agitation granulation, granules made by fluidized-bed granulation showed superior compressibility with wide formulation allowance for drug type and amount. Fluidized-bed granulation resulted in less granule hardness and greater plastic deformability. The granules had considerable compactness and for tablets containing 70% ethenzamide, prolonged disintegration and dissolution times were noted. These are typical features of granules produced by fluidized-bed granulation.

Acetaminophen↗

Multiple appearing and vanishing aneurysms: primary angiitis of the central nervous system. Case report.

The authors present the case of a patient with ischemic episodes and recurrent intracerebral hemorrhages probably caused by primary angiitis of the central nervous system (CNS). An initial angiogram revealed multiple cerebral artery aneurysms as well as vascular wall irregularity; a second angiogram obtained 2 years later, however, did not demonstrate the previous aneurysms but instead showed new ones together with stenosis. Based on the histopathological findings and clinical course in this case, the multiple aneurysms appear to have been induced by vascular wall fragility and subsequent self-repair resulting from primary angiitis of the CNS. The authors present the histological and clinical characteristics of this unusual case of granulomatous, necrotizing CNS vasculitis.

Central Nervous System Diseases↗

[A tuberculosis epidemic among four relatives who live in the neighborhood of index case].

A tuberculosis epidemic occurred among 4 relatives who live in the neighborhood of the index case. A thirty-three year old female was admitted to a hospital in July 1994 with high fever and cervical lymphoadenopathy. Culture examination of her sputum was positive for acid-fast bacilli and her chest X-ray showed diffuse small nodules. During the following sixteen months, five new patients with pulmonary tuberculosis were found among the relatives who lived in the neighborhood of the index case. The contact examination was first limited in her own family members, however, after detection of the second case, the examination was extended to other relatives living nearby, and another four patients were found. The results of PPD skin test of ten contact children showed strongly positive reaction, and chemoprophylaxis was indicated. Contacts examination is very important especially for patients with highly infectious tuberculosis.

Adolescent↗

[MPO-ANCA related diffuse alveolar hemorrhage].

The purpose of this study was to elucidate the clinical features characterizing patients with myeloperoxidase specific-antineutrophil cytoplasmic antibody (MPO-ANCA) related diffuse alveolar hemorrhage (DAH). Seventeen MPO-ANCA-positive patients were evaluated. Nine patients (52.9%) had pulmonary involvement; of those, 6 (35.3%) had DAH, and 4 (23.5%) had interstitial pneumonia (1 patient had both pulmonary diseases). Three of the patients with DAH demonstrated only mildly bloody sputum. All patients with DAH had increased peripheral white blood cell counts, high titers of C-reactive protein and MPO-ANCA, and marked microscopic hematuria. DAH was diagnosed in all cases by fiberoptic bronchoscopy with bronchoalveolar lavage. All patients with DAH were treated with three pulses of methylprednisolone, and 5 were treated with cyclophosphamide. Three of the patients with DAH required mechanical ventilation for respiratory insufficiency, but 2 were relieved of that need by immunosuppressive therapy. In spite of intensive care, 1 patient died of respiratory failure and 2 died of complications related to therapy. The prognosis for patients with DAH is poor. We emphasize the importance of prompt and accurate diagnoses and aggressive care, including immunosuppressive therapy, mechanical ventilation, and hemodialysis. In addition, extra precautions should be taken against opportunistic infections such as Pneumocystis carinii pneumonia.

Aged↗