Biomedical subjects

K Shimizu

Publications and source records attributed to K Shimizu.

At least 595 records · Page 33Linked to original sources

PubMed1997

Effects of various selective phosphodiesterase inhibitors on muscle contractility in guinea pig ileal longitudinal smooth muscle.

The effects of various selective phosphodiesterase (PDE) inhibitors on muscle contractility in guinea pig ileal longitudinal smooth muscle were investigated. 1) 3-Isobutyl-1-methyl xanthine (IBMX) or zaprinast markedly inhibited the high K(+)- or carbachol (CCh)-induced contraction and increased cGMP content of the muscle strip in a concentration-dependent manner. However, these agents only slightly increased the cAMP content. Milrinone or Ro20-1724 also slightly inhibited the high K(+)- or CCh-induced contraction and increased the cAMP content, but did not increase cGMP. 2) In a fura2-loaded muscle, IBMX or zaprinast inhibited both contractions and the increase in intracellular Ca2+ ([Ca2+]i) level induced by high K+ or CCh, although the inhibitory effect on the [Ca2+]i level was smaller than that on muscle tension. 3) In alpha-toxin-permeabilized muscles, cGMP, IBMX or zaprinast significantly inhibited the Ca(2+)-induced contraction. These results suggest that IBMX and zaprinast inhibit muscle contraction in the ileal longitudinal smooth muscles mainly through an increase in cGMP and the inhibitory mechanism of IBMX or zaprinast is involved in the decreases in the [Ca2+]i level and sensitivity of contractile elements to Ca2+.

1-Methyl-3-isobutylxanthine↗

PubMed1997

Preferential changes in hepatosplanchnic hemodynamics in patients with borderline hypertension.

To investigate changes in systemic and regional hemodynamics during the development of human hypertension, we simultaneously measured cardiac index (CI) by the indocyanine green (ICG) dye dilution method, hepatosplanchnic blood flow (HBF) by the ICG clearance method using a two-compartment model, and renal blood flow (RBF) by the p-aminohippurate clearance method in patients with borderline and essential hypertension. In patients with borderline hypertension (BH, n = 27), HBF (435 +/- 15 ml/min/m2) and HBF/CI (16 +/- 1%) were significantly (p < 0.05) lower than in age-matched normotensive controls (528 +/- 21 and 19 +/- 1, respectively, n = 21), while CI, RBF and RBF/CI were similar. In patients with essential hypertension (EH, n = 32), HBF, RBF, and RBF/CI were all significantly (p < 0.01) lower than in the control subjects. Hepatosplanchnic vascular resistance (HVR) in patients with BH was preferentially increased, while total peripheral resistance (TPR) and renal vascular resistance (RVR) remained in the normal range. In patients with EH, TPR, HVR, and RVR were all increased. These results indicate that hemodynamic changes in patients with BH do not occur uniformly among the various regional circulations and suggest that hemodynamic changes in the hepatosplanchnic region precede those in other organ circulations during the development of human hypertension.

Adolescent↗

PubMed1997

Suppression of glucose absorption by some fractions extracted from Gymnema sylvestre leaves.

Extracts containing gymnemic acids, which were extracted from the leaves of Gymnema sylvestre (GS) as nine fractions, were evaluated for their effects on a high K(+)-induced contraction of guinea-pig ileal longitudinal muscles, on glucose transport mediated by the difference of glucose-evoked transmural potential difference (delta PD) in the inverted intestine of guinea-pig and rat, and on blood glucose in rat. Among nine fractions obtained by high performance liquid chromatography from the extract, f-2 and f-4 strongly suppressed the high K(+)-induced contraction of the ileal muscle, f-3 and f-5 did so moderately, and f-8 and f-9 did so weakly, whereas the other fractions did not affect it. The degree of suppression of high K(+)-induced contraction by f-2 at 74% was almost the same as that of f-4 at 67%, at concentrations of 0.1 mg/ml. The suppressed contraction by f-2 or f-4 was recovered by adding 5.5 mM pyruvate. The delta PD increased by 5.5 mM glucose in the inverted intestines of guinea-pig and rat were equally suppressed by 0.1 mg/ml of f-2 or f-4 to 40%. In a rat sucrose tolerance test, f-2 and f-4 suppressed the elevation of blood glucose level. Both f-2 and f-4 suppressed the contraction of guinea-pig ileal longitudinal muscle, interfered with the increase in delta PD induced by glucose in the inverted intestines of guinea-pig and rat, and inhibited the elevation of blood glucose level. In conclusion, it is suggested that some of the extracts containing gymnemic acids from GS leaves suppress the elevation of blood glucose level by inhibiting glucose uptake in the intestine.

Administration, Oral↗

PubMed1997

Suppression of glucose absorption by extracts from the leaves of Gymnema inodorum.

Gymnema sylvestre (GS) is one of the Asclepiad strains that grows in South-east Asia. Their therapeutic effects for treating diabetes mellitus, rheumatic arthritis and gout have been well known for a long time. However, the problem is that GS suppresses sweetness and tastes bitter. For this study, we chose Gymnema inodorum (GI) instead of GS, since it has an advantage that it does not suppress sweetness nor is it bitter in taste. In this paper, effects of glucose availability of some saponin fractions (F-I to F-IV) extracted from GI leaves, which were obtained by high-performance liquid chromatography were studied on a high K(+)-induced contraction of guinea-pig intestinal smooth muscle, O2 consumption on guinea-pig ileum, glucose-evoked transmural potential difference (delta PD) of guinea-pig everted intestine and blood glucose level in glucose tolerance tests on rats. The extracts of GI leaves suppressed the intestinal smooth muscle contraction, decreased the O2 consumption, inhibited the glucose evoked-transmural potential, and prevented the blood glucose level. Our studies suggest that the component of GI inhibits the increase in the blood glucose level by interfering with the intestinal glucose absorption process.

Animals↗

PubMed1997

Osteonecrosis of the femoral head: a prospective study with MRI.

We performed a prospective study using MRI to evaluate early necrosis of the femoral head in 48 patients receiving high-dose corticosteroids for the treatment of various autoimmune-related disorders. The mean interval from the initiation of corticosteroid therapy to the first MRI examination was 2 months (0.5 to 6). MRI was repeated, and the mean period of follow-up was 31 months (24 to 69). Abnormalities were found on MRI in 31 hips (32%). The initial changes showed well-demarcated, band-like zones which were seen at a mean of 3.6 months after initiation of treatment with steroids. In 14 of these hips (45%) there was a spontaneous reduction in the size of the lesions about one year after treatment had started, but there was no further change in size with a longer follow-up.

Adolescent↗

PubMed1997

Plasma chromogranin A in pheochromocytoma, primary hyperparathyroidism and pituitary adenoma in comparison with catecholamine, parathyroid hormone and pituitary hormones.

Plasma levels of chromogranin A (CgA) were measured by ELISA in 22 patients with pheochromocytoma (18 non-metastatic, 3 metastatic, and 1 mixed neuroendocrine-neural tumor), 9 patients with primary hyperparathyroidism, and 9 patients with pituitary adenoma. The plasma levels of CgA were compared with norepinephrine, epinephrine, parathyroid hormone and pituitary hormones, i.e., growth hormone and prolactin. In pheochromocytoma, CgA in preoperative plasma of the patients without metastasis was 228 +/- 38 U/L (mean +/- SEM) and significantly higher than healthy controls (30 +/- 11 U/L, n = 40). Plasma CgA was decreased after removal of the tumors (28 +/- 6.0 U/L), except in three patients with metastatic pheochromocytoma and a mixed neuroendocrine neural tumor. The concentration of CgA in the patients with non-metastatic pheochromocytoma was significantly correlated with that of plasma norepinephrine (P < 0.005, r = 0.68) and urinary norepinephrine (P < 0.05, r = 0.65), but not with that of epinephrine. There was an exceptional case in which CgA was extremely high, but the CA level was normal. This tumor was a highly malignant pheochromocytoma with extensive metastases composed of small tumor cells which were occasionally positive for tyrosine hydroxylase immunohistochemically. These cells were considered to be poorly differentiated tumor cells and synthesized a very small amount of norepinephrine. Plasma levels of the patients with primary hyperparathyroidism and the patients with pituitary adenoma were 44 +/- 4 U/L and 48 +/- 8 U/L, respectively. Only one patient with a growth hormone-producing pituitary adenoma had a high level of CgA. Plasma CgA is a useful tumor marker for pheochromocytoma, even for malignant pheochromocytoma without elevated CA level, but not for hyperparathyroidism, or pituitary adenoma.

Adenoma, Acidophil↗

PubMed1997

Danazol induced thrombocytopenia.

A 34-year-old woman with a left ovarian cyst (clinically diagnosed as endometrial cyst) was treated with 400 mg of danazol per day. On the next day, after a total dose of only 600 mg of danazol, gingival bleeding and purpura occurred. Her laboratory findings were as follows: platelet count 1000/ mm3 hematocrit 39%, WBC 7300/mm3 and RBC 466 x 10(4)/mm3. Immune thrombocytopenic purpura (ITP) was diagnosed, and she was treated with 40 mg of methylprednisolone per day for 19 days. Her platelet count increased to 130,000/ mm3. Her left ovarian cyst was extirpated surgically, and the histological diagnosis was endometrial cyst. Danazol at 400 mg per day was therefore again administered. On the next day, she complained of gingival bleeding and purpura again, and her platelet count was 5000/mm3. We diagnosed this case as danazol induced thrombocytopenia.

Adult↗

PubMed1997

Enchondroma of the distal phalanx of the hand.

We saw five patients who had enchondroma of the distal phalanx, a relatively uncommon site for that lesion. Three patients had pain secondary to a pathological fracture and were managed with curettage and bone-grafting through a palmar longitudinal incision. The other two patients had severe deformities of the fingertip and nail. One was managed with disarticulation of the distal interphalangeal joint and the other, with curettage and grafting through a dorsal approach followed by reconstruction of the nail matrix. We believe that the palmar incision in the pulp of the finger has few, if any, complications.

Adult↗

PubMed1997

[Toxicity studies of landiolol hydrochloride (ONO-1101) (2). 4-week repeated dose intravenous toxicity study in rats with 4-week recovery test].

4-week repeated dose toxicity study with 4-week recovery test of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in Sprague-Dawley (SD) rats. ONO-1101 was administered intravenously to rats of both sexes at a dose level of 0 (control), 12.5, 25, 50 or 100 mg/kg/day. In the 100 mg/kg/day group, bradypnea or dyspnea was seen in all animals, pale in ear, eye and foot, tremor, reddish lacrimation and loss of righting reflex were also observed in some animals right after administration, and then those signs disappeared within 1 min after administration. During the treatment period, 3/20 animals of each sex in the 100 mg/kg/day showed clonic convulsion and died within 2 min after administration. No clinical changes were seen in the 50 mg/kg/day group or lower. Histopathological findings showed atrophy of the submaxillary gland in females and vessel-wall thickening and perivascular fibrosis of the injection site (tail) in both sexes at 100 mg/kg/day, however those changes were reversible. ONO-1101 did not effect on body weight, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weights or necropsy at any doses. These results indicate that the no-adverse-effect level of ONO-1101 in rats is 50 mg/kg/day for both sexes in this study.

Adrenergic beta-Antagonists↗

PubMed1997

[Toxicity studies of landiolol hydrochloride (ONO-1101) (3). 4-week repeated dose intravenous toxicity study in dogs with 4-week recovery test].

4-week repeated dose toxicity study with 4-week recovery test of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in beagle dogs. ONO-1101 was administered intravenously to dogs of both sexes at a dose level of 0 (control), 12.5, 25 or 50 mg/kg/day. No deaths occurred throughout the treatment period. Transitory licking chops, vomiting, nausea, diarrhea and soft feces were observed occasionally in both sexes dosed 25 and 50 mg/kg/day and the incidence seemed dose-dependent. However, those incidence declined in the course of the treatment period. Hematology showed a decrease in red blood cell count, hematocrit and hemoglobin value in both sexes receiving 25 and 50 mg/kg/day. ONO-1101 did not effect on body weight, food consumption, respiratory rate, pulse, rectal temperature, heart rate, blood pressure, electrocardiography, renal or hepatic function, ophthalmology, urinalysis, occult blood in feces, blood chemistry, organ weights, necropsy and microscopic findings at any doses. These results indicate that the no-adverse-effect level of ONO-1101 in dogs is 12.5 mg/kg/day for both sexes in this study.

Adrenergic beta-Antagonists↗

PubMed1997

Cushing's syndrome due to bilateral adrenocortical adenomas with different pathological features.

A 48-year-old woman with Cushing's syndrome due to bilateral adrenocortical adenomas is reported. The patient presented with a typical Cushingoid appearance. The serum cortisol level was elevated with loss of the diurnal rhythm and the plasma adrenocorticotropic hormone (ACTH) level was undetectable. Dynamic testing showed no suppression of urinary 17-OHCS by high-dose dexamethasone and no stimulation by metyrapone. An abdominal computed tomography (CT) scan showed bilateral adrenal tumors. Bilateral adrenalectomy was performed. The right adrenal gland contained a tumor that was encapsulated and consisted mainly of compact cells. The surrounding cortex was atrophic. The left adrenal gland contained an encapsulated tumor composed predominantly of clear cells. There were numerous small adrenocortical nodules in the surrounding cortex. Immunohistochemical analysis of steroidogenic enzymes (P450scc, 3beta-HSD, P450c21, P450c17 and P450c11) was performed. Immunoreactivity of all the enzymes was intense in the compact cells of the right adrenocortical adenoma, while the adjacent non-neoplastic cortex was negative for the enzymes. In the left adrenal tumor, the immunoreactivity of 3beta-HSD was intense, while that of P450c17 was weak. In the adrenocortical nodules, 3beta-HSD activity was sporadically observed. G protein genes encoding Gs alpha and Gi2 were examined for activating mutations at codons 201 and 227 (Gs alpha) and codons 179 and 205 (Gi2 alpha) in the bilateral adrenal tumors, but no mutations were found. The bilateral adenomas of this patient showed marked differences in microscopic and immunohistochemical studies, suggesting that the capacity of steroidogenesis differs between the right and left tumors.

Adrenal Cortex Neoplasms↗

PubMed1997

Total anomalous pulmonary vein drainage in an adult diagnosed by helical computed tomography.

A 41-year-old man visited our hospital with the complaint of palpitation by atrial flutter. He was finally diagnosed as total anomalous pulmonary vein drainage by helical computed tomography (CT). This case is very unusual due to the lack of symptoms until the age of 41. The absence of pulmonary artery stenosis, and the presence of atrial septal defect providing sufficient right to left shunt flow to maintain the output of left ventricle are some of the reasons to explain the lack of symptoms and very slight impact on daily life. Helical CT, in particular 3-dimensional imaging, is very useful in diagnosing complicated cardiovascular deformation as in this case.

Adult↗

PubMed1997

Intraoral minor salivary gland tumors: a retrospective study of 129 cases.

From 1970 to 1996, 129 cases of intraoral minor salivary gland tumors were diagnosed at the Department of Pathology, Nihon University School of Dentistry. The diagnosis of each case was based on the 1991 WHO classification. Eighty benign and 49 malignant minor salivary gland tumors were found in the approximately 9,300 oral biopsies submitted during the 27-year period. Pleomorphic adenomas were the most commonly histologic type of the benign tumors identified and 51% of the malignant tumors were diagnosed as mucoepidermoid carcinoma. The most common primary location of the tumors was the palate. Sixty percent of all tumors occurred in females and the peak age for incidences of all tumors was found in the third, fourth, sixth and seventh decades. These results were compared with those of the studies in different world population groups.

Adenoma, Pleomorphic↗

PubMed1997

[Lipid and lipoprotein profile of Japanese centenarians--high prevalence of hypo beta lipoproteinemia].

To study the relationship between lipids and longevity, we examined the level of serum lipids and apolipoproteins, and the susceptibility of low density lipoprotein (LDL) to oxidation of 45 centenarians (15 men, 30 women, mean age 101.1 +/- 1.4) living in the Tokyo metropolitan area. The average levels of total cholesterol (TC), of LDL-C of high-density lipoprotein cholesterol (HDL-C), and of apolipoproteins A1 and B were significantly lower in centenarians than in healthy middle-aged controls. The frequency of hypobeta-lipoproteinemia (apoB < 60 mg/dl) in centenarians was almost ten times as high as in controls. The time course of copper-mediated LDL, oxidation (assessed by monitoring 234 nm diene absorption (lag time)) did not significantly differ between the two groups. Analysis of LDL subfractions by non-denaturated gradient-gel electrophoresis showed a predominance of large, buoyant LDL particles (pattern A) in 75%, and a predominance of small dense LDL particles (pattern B) in 25% of centenarians. We also assessed activities of daily living (ADL) and cognitive function in the centenarians. Centenarians were divided into two groups according to the median ADL score, and were classified into five groups with a scale clinical dementia. In subjects with good ADL scores, the mean concentration of HDL-3-C was significantly higher than in those with poor ADL scores. Average levels of HDL-C were also significantly lower in subjects with moderate or severe dementia than in those with normal cognitive function. These findings suggest that centenarians have protective phenotypes of lipids and lipoproteins that protect them from atheroscierosis.

Activities of Daily Living↗

PubMed1997

[Tokyo Centenarian Study. 4. Apolipoprotein E phenotype in Japanese centenarians living in the Tokyo Metropolitan area].

To examine the relationship between apolipoprotein E (apoE) phenotype and life span, we measured the frequently of the apoE phenotype and allele in 54 Japanese centenarians who lived in the Tokyo metropolitan area in 1994, 1995, and 1996. The control group consisted of 973 subjects, 883 healthy volunteers who were described previously and 90 healthy people who came to the Keio health consulting center. The apoE phenotypes in the centenarians was 2 E2/E2 (3.7%), 5 E2/E3 (9.3%), 38 E3/E3 (70.4%), and 9 3E/E4 (16.7%). No other phenotype was observed. In the control group, the phenotypes were 2 E2/E2 (0.2%), 57 E2/E3 (5.9%) 712 E3/E3 (73.2%), and 179 E3/E4 (18.4%). The frequency of E2 was higher in the centenarians. The frequencies of the apoE allele in the centenarians and the control subjects were epsilon 2 8.3% vs. 3.5%, epsilon 3 83.3% vs. 85.4%, and epsilon 4 8.3% vs. 10.9%. The frequency of the apoE allele differed significantly between centenarians and control subjects (chi 2 = 6.84, p = 0.033). Levels of serum cholesterol and apolipoprotein B were significantly lower in the E2/E2 + E2/E3 centenarians. Studies of the frequency of the apoE allele in Japanese, French, and Finnish subjects showed that epsilon 2 is more frequent and epsilon 4 is less frequent in centenarians. These data show the apoE phenotype may affect life span: epsilon 2 is positively and epsilon 4 is negatively associated with longevity.

Aged↗

PubMed1997

[Tokyo Centenarian Study. 5. Nutritional status of Japanese centenarians].

To establish the guideline for nutrition in the very old, we analyzed biochemical and hematological data from 45 Japanese centenarians living in Tokyo metropolitan area during 1994 and 1995. Levels of cholesterol, HDL-cholesterol, apolipoprotein A1 and B, albumin, prealbumin in serum were lower than in a control group or lower than the reference range, which indicates that these centenarians were undernourished. RBC counts, hemoglobin, and hematocrit were also low in the centenarians. The concentration of albumin correlated positively with those of HDL-cholesterol and apolipoprotein A1, and negatively with concentration of Lp(a). The value for transferrin correlated positively with energy intake and with the concentration of apolipoprotein A1. The concentration of prealbumin correlated positively with the concentration of hemoglobin, hematocrit and the total cholesterol concentration. According to their nutritional status, the centenarians were divided into 2 groups: well-nourished and undernourished. Those who were well-nourished had higher levels of cholesterol, HDL, Hb, and apolipoprotein A1, their levels of ADL and cognitive function were also high. The findings of blood-chemical data in the centenarians may be partly due to undernutrition. Centenarians who were well-nourished were considered to be aging successfully. These results and others previously published indicate that the concentrations of albumin, prealbumin, transferrin and either CRI or IL-6 are useful for nutritional assessment in the very old.

Aged↗

PubMed1997

Noninvasive optical imaging of the subarachnoid space and cerebrospinal fluid pathways based on near-infrared fluorescence.

The authors have developed a noninvasive optical method to image the subarachnoid space and cerebrospinal fluid pathways in vivo based on the near-infrared fluorescence of indocyanine green (ICG). The ICG was bound to purified lipoproteins (ICG-lipoprotein) and injected into the subarachnoid space of neonatal and adult rats. The ICG fluorescence was detected by a cooled charge-coupled device camera. After injection of ICG-lipoprotein into the cerebral subarachnoid space of the neonatal rat, ICG fluorescence was clearly detected at the injection site through the skull and skin. The ICG fluorescence was observed in the cerebellum and the lumbar spinal cord 1 and 8 hours postinjection, respectively. After injection of ICG-lipoprotein into the lumbar spinal subarachnoid space of an adult rat, ICG fluorescence was observed from the injection site to the thoracic levels along the spinal subarachnoid space. In addition, with the rat's head tilted downward, ICG fluorescence had extended to the cerebral subarachnoid space by 1 hour postinjection. The ICG fluorescence imaging of the cerebral subarachnoid space demonstrated an increase in fluorescence intensity around the lambdoid suture and the forebrain. On dissection of the rat brain the former location was identified as the supracerebellar cistern and the latter as the olfactory cistern. The results of this study are the first to demonstrate that an optical technique is applicable to imaging of the subarachnoid space and cerebrospinal fluid pathways in vivo. In addition, ICG-lipoprotein provides a sensitive optical tracer for imaging extravascular biological structures. Finally, ICG fluorescence imaging does not require an intricate imaging system because ICG is localized near the surface of the body.

Animals↗

PubMed1997

A long-term clinical study on drawn poly-L-lactide implants in orthopaedic surgery.

We have developed an ultra-high-strength drawn poly (L-lactide) (PLLA) with a bending strength of 240 MPa. Seventy-four patients (80 cases) who were treated with this PLLA implant were enrolled in this study. Their ages ranged from 14 to 78 years, and the follow-up period ranged from 4 to 9 years (mean: 5.3 years). Bony union was obtained in all cases. Osteolytic changes were observed in 12 cases (15%) but no late aseptic swelling was noted. Both MRI and roentgenographic findings indicated that the spaces where the PLLA implants were located had not been replaced with bony tissue.

Adolescent↗