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Biomedical subjects

N Yamada

Publications and source records attributed to N Yamada.

At least 415 records · Page 23Linked to original sources

Left ventricular thrombosis following coronary artery bypass grafting in a patient with nephrotic syndrome: report of a case.

We present herein the case of a 63-year-old man with nephrotic syndrome who developed an apical infarction 4 days after undergoing coronary artery bypass grafting. Echocardiography done 2 weeks postoperatively revealed a left ventricular thrombus which was successfully removed. He has no further thrombotic events since anticoagulant therapy was initiated.

Coronary Artery Bypass↗

Antimicrotubule effects of the novel antitumor benzoylphenylurea derivative HO-221.

The antitumor action of HO-221, a novel benzoylphenylurea derivative, was studied. The in vitro cytotoxic strength of HO-221 was investigated, as measured by IC50 values, compared with those of other drugs with different action mechanisms, using Chinese hamster lung (CHL) cells, mouse leukemia L1210 cells and human promyelocytic leukemia HL-60 cells. Morphological alterations following treatment were observed under a phase contrast microscope, and the mitotic index was determined at regular intervals to check for accumulation of metaphase cells. HO-221 was found to have a very strong toxic effect on all cell types, equal to that of the spindle poisons used as controls. HO-221 also produced the same specific morphological changes as the spindle poisons, with a significant accumulation of metaphase cells. A chromosome analysis of treated cells showed that HO-221 frequently induced polyploid and aneuploid cells, but without accompanying chromosome-breaking activity. An in vivo mouse bone marrow micronucleus assay was also carried out. The assay allowed the in vivo identification of a chromosome breaker or a spindle poison through the measurement of the relative sizes of micronuclei produced and erythrocytes. HO-221 was found frequently to induce relatively large micronuclei, an action regarded as specific to spindle poisons. It was thus demonstrated that HO-221 acts as a spindle poison both in vitro and in vivo. In order to investigate the mechanism of this action, a study of tubulin assembly using purified calf brain tubulin was carried out, which demonstrated clearly that HO-221 inhibits microtubule assembly. A detailed investigation of the action mechanism of HO-221 as a spindle poison is now called for.

Animals↗

Steatorrhea in Japanese patients with chronic pancreatitis.

Fecal fat excretion, fecal mass, fecal fat concentration, and the coefficient of fat absorption were evaluated in 31 normal Japanese subjects with a mean fat consumption of 61.8 g and compared with the values in 43 Japanese patients with chronic pancreatitis (CP) with a fat consumption of 40.2 g. Fecal fatty acids were analyzed by the gas chromatographic method. Fecal fat excretion by normal individuals was 1.7 +/- 1.0 (Mean +/- SD) g/day (range, 0.4-4.9 g/day). Steatorrhea was therefore defined as fecal fat excretion that exceeded 5.0 g/day. The patients with CP were divided into three groups: non-steatorrhea (fecal fat < 5.0 g/day), chemical steatorrhea (fecal fat > or = 5 g/day and no appearance of fatty stool), and manifest steatorrhea (evaluated from the appearance of fatty stool). In addition, we investigated the correlation between fecal fat excretion and pancreatic exocrine function, obtained by the pancreozymin-secretin (or secretin) test in 24 controls and 30 CP patients. Fecal fat excretion by CP patients was 9.1 +/- 8.8 g/day, which was significantly higher (P < 0.01) than that of controls. There were 28 (65%) CP patients with steatorrhea. Of these, 15 (35%) showed chemical steatorrhea and 13 (30%) manifest steatorrhea. In CP patients, the fecal mass (250.5 +/- 133.6 g vs control, 125.6 +/- 52.5 g), fecal fat concentration (3.40 +/- 2.16 g% vs control, 1.48 +/- 0.89 g%), and coefficient of fat absorption (77.3 +/- 20.2% vs control, 97.2 +/- 1.7%) all showed significant differences from the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Role of SPan-1 antigen in adhesion of human colon cancer cells to vascular endothelium.

Recently E-selectin (ELAM-1, endothelial leukocyte adhesion molecule-1) was shown to recognize not only sialyl Lewis X but also sialyl Lewis A, and these carbohydrate antigens may be involved in the process of the adhesion between cancer cells and endothelial cells in cancer metastasis. To investigate the contribution of sialylated carbohydrate antigen, SPan-1, and sialic acid to the adhesion of human colon cancer cells to endothelial cells, adhesion assay using HUVECs (human umbilical vein endothelial cells) was performed. The adhesion was significantly inhibited by pretreatment with anti-E-selectin antibody, indicating that this adhesion was thought to be mediated by E-selectin. When these cancer cells were pretreated with SPan-1 antibody, the adhesion was significantly inhibited in a concentration-dependent manner. The adhesion was also inhibited by pretreatment with neuraminidase. These findings suggest that the SPan-1 antigen plays a significant role in the adhesion of human colon cancer cells to endothelial cells, and sialylation of the terminal structure of carbohydrate antigens is important in this adhesion.

Antigens, Neoplasm↗

No negative feedback regulation between plasma CCK levels and luminal tryptic activities in patients with pancreatic insufficiency.

The study was conducted on five healthy subjects and six patients with calcifying pancreatitis (CP) and steatorrhea. Following overnight fasting, one tube each was placed in the stomach and the upper of the small intestine, respectively. Through the gastric tube, a test meal that included 30 g of fat (total calories, 625 kcal, 500 mL) was infused over a span of 30 min. Every 30 min (up to 150 min), fluid samples in the upper small intestine were collected and chilled, and the amylase, trypsin, and lipase levels were determined. In addition, in the case of the CP patients, a high-potency pancreatin preparation was infused into the stomach together with the test meal. In order to determine the plasma CCK level, blood sample were collected before test meal infusion and at 10, 20, 30, 45, 60, 90, 120, and 150 min subsequent to infusion. The plasma CCK was extracted using a Sep-Pak C-18 cartridge and analyzed with radioimmunoassay using an OAL-656 antibody. The result was converted to the CCK-8 level and expressed in pg/mL. The enzyme activities in the upper small intestine of the CP patients after test meal administration amounted to 22.8 (amylase), 10.8 (trypsin), and 16.9% (lipase) compared with the corresponding figures for the normal subjects. Following administration of a high-potency pancreatin in patients with CP, enzyme activities in the upper small intestine increased to 132.2 (amylase), 38.7 (trypsin), and 45.3% (lipase) compared with levels in the normal subjects. However, the healthy subjects and the CP patients, both with and without treatment with supplementary exogenous enzymes, all exhibited similar profiles in the plasma CCK response to stimuli. Based on these findings, we concluded that a negative feedback mechanism does not exist between the tryptic activity of the upper small intestine and the CCK secretory response in patients with chronic pancreatitis.

Adult↗

Relationship between insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus: beta-cell function, islet cell antibody, and haptoglobin in parents of IDDM patients.

To examine the relationship between non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM), we studied beta-cell function, HLA type, and serologic markers of IDDM and NIDDM in the parents of IDDM patients. Fifty-two parents of 33 IDDM patients were examined in terms of islet-cell antibody (ICA) status, haptoglobin phenotype, HLA type, and insulin responses during an oral glucose tolerance test (OGTT). Twenty-seven parents were prospectively evaluated for up to 113 months. They were divided into the following three groups based on pattern of ICA positivity during the follow-up period: group 1, persistently positive ICA (n = 4); group 2, fluctuating ICA (n = 7); and group 3, persistently negative ICA (n = 16). Twenty-three percent (12 of 52) of the parents of IDDM patients had NIDDM, and 12% (six of 52) of the matched controls did. The prevalence of ICA in the parents (11 of 52, 21%) was greater than in normal controls (one of 112, P < .01). Diabetic parents tended to show a higher prevalence of ICA (six of 12, 50%) than nondiabetic parents (six of 40, 15%; P = .06). ICA-positive parents showed higher glucose levels and lower insulin responses than ICA-negative parents. Three of four parents in group 1 slowly progressed to an insulin-dependent state during 25 +/- 3 months of follow-up evaluation. Parents in group 2 and group 3 did not show any changes in glucose levels or insulin responses during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Mechanism of cell detachment from temperature-modulated, hydrophilic-hydrophobic polymer surfaces.

Poly(N-isopropylacrylamide) (PIPAAm), exhibiting a lower critical solution temperature (LCST) at 25 degrees C in physiological phosphate buffered saline solution (pH 7.4) and at 32 degrees C in pure water, was grafted onto the surfaces of commercial polystyrene cell culture dishes. This PIPAAm-grafted surface exhibited hydrophobic surface properties at temperatures over the LCST and hydrophilic surface properties below the LCST. Endothelial cells and hepatocytes attached and proliferated on PIPAAm-grafted surfaces at 37 degrees C, above the LCST. The cultured cells were readily detached from these surfaces by lowering the incubation temperature without the usual damage associated with trypsinization. In this case, the optimum temperature for cell detachment was 10 degrees C for hepatocytes and 20 degrees C for endothelial cells. Cell detachment was partially inhibited by sodium azide treatment, suggesting that cell metabolism directly affects cell detachment. Morphological changes of the adherent cells during cell detachment experiments indicated further involvement of active cellular metabolic processes. Cells detached from hydrophobic-hydrophilic PIPAAm surfaces not only via reduced cell-surface interactions caused by the spontaneous hydration of grafted PIPAAm chains, but also by active cell morphological changes which were a function of cell metabolism.

Acrylic Resins↗

Sequential MR signal change of the thrombus in the false lumen of thrombosed aortic dissection.

The evolution of thrombus in the false lumen was investigated in 14 patients with thrombosed aortic dissection, by reviewing the findings acquired at a total of 21 magnetic resonance imaging (MRI) examinations performed between 2 and 146 days after the onset. On electrocardiographic gated 1.5-Tesla MRI, T1-(TR/TE = 860 +/- 190 ms/17-40 ms) and T2-(TR/TE = 1620 +/- 240 ms/70-80 ms) weighted spin echo and gradient echo images were obtained, and the signal intensity of the thrombus on these images was evaluated independently by two observers. The density of the thrombus was also evaluated using computed tomography (CT) images obtained at a total of 54 examinations. On both T1- and T2-weighted images, the thrombus showed signal iso- or hypointensity compared to that of skeletal muscle during the first several days after the onset and, thereafter, showed signal intensity similar to that of fat tissue. It is suggested that the low signal intensity of the thrombus observed during the initial period after the onset was caused by the presence of deoxyhemoglobin and the high intensity observed thereafter was caused by methemoglobin. Focal discrepancy of the signal intensities within two parts of the lumen on spin echo images was observed in 7 patients, and a low-intensity layer on the surface of the thrombus inside the false lumen was observed on gradient echo images in 5 of these 7 patients. This characteristic MR signal change of the thrombus in the false lumen of thrombosed aortic dissection provides useful information concerning the age of the thrombus and in the differential diagnosis of the thrombus from a mural thrombus of aortic aneurysm.

Adult↗

Chronologic analysis of in situ cytokine expression in mite allergen-induced dermatitis in atopic subjects.

Patch testing with crude dust mite extracts, after removal of horny epidermal layers, was performed on normal-appearing skin of nine adult patients with atopic dermatitis who had high mite-specific IgE antibody levels. Positive skin reactions were observed in seven subjects. Skin biopsy specimens were obtained from positive reaction sites at 2, 6, 12, 24, and 48 hours after allergen challenge and subjected to histologic and immunohistochemical studies and extraction of RNA. Perivascular infiltration of small mononuclear cells began at 2 hours, followed by eosinophilic infiltration at 6 hours, which peaked at 24 and 48 hours. Increased expression of IL-4 messenger RNA was detected with reverse-transcription polymerase chain reaction at 12 and 24 hours, whereas immunohistochemical staining with anti-IL-4 antibody showed positive reactions in connective tissue around infiltrating cells after 2 hours. Expression of IL-5 and tumor necrosis factor-alpha mRNA was upregulated 2 hours after an application of allergen. Interferon-gamma mRNA was not detected. These findings suggest the crucial role of TH2-type cytokines in initiating eosinophil infiltration of mite allergen-induced dermatitis in patients with atopic dermatitis.

Adult↗

Establishment of a new human extrahepatic bile duct carcinoma cell line (OCUCh-LM1) and experimental liver metastatic model.

A new human extrahepatic bile duct carcinoma cell line, designated OCUCh-LM1, was established from a liver metastatic lesion in a 61-year-old male. OCUCh-LM1 cells proliferated in a monolayered sheet with a population doubling time of 31 h. OCUCh-LM1 cells had an aneuploid pattern with a DNA index of 1.76, and chromosome counts showed a unimode of 63. OCUCh-LM1 cells expressed various carbohydrate antigens, including sialyl Lewis X, carbohydrate antigen 19-9 and SPan-1 antigen. Subcutaneous injections of OCUCh-LM1 cells induced tumour formation in nude mice. The reconstituted tumours were classified as well-differentiated adenocarcinoma. A daughter line, designated OCUCh-LM1-H1, was also established from liver metastatic colonies induced by splenic injection of OCUCh-LM1. OCUCh-LM1-H1 cells showed a higher potential for liver metastasis than OCUCh-LM1 (100% vs 20%). Since OCUCh-LM1 retains the initial characteristics (as of 93 passages at present) and expresses various carbohydrate antigens, the OCUCh-LM1 cell line and liver metastatic model established here will be useful for the study of the biological nature of extrahepatic bile duct carcinoma and the relationship between the expression of carbohydrate antigens and metastatic potential.

Animals↗

Suppression of mitochondrial succinate dehydrogenase, a primary target of beta-amyloid, and its derivative racemized at Ser residue.

beta-Amyloid cores contain considerable amounts of D-Ser and D-Asp residues in Alzheimer's disease. We investigated the cytotoxic effects of various synthetic beta-amyloids, including D-Ser-substituted derivatives, on primary cultured neurons and nonneuronal HeLa cells. beta 25-35, its D-Ser26-substituted derivative, and beta 1-40 in 10-100 nM specifically suppressed mitochondrial succinate dehydrogenase activity [MTT [3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide] reduction] in HeLa cells, which are dependent on ATP production mainly from glycolysis, but did not exert detectable cytotoxicity, assessed by dye exclusion test, NADH levels, and uptake of [3H]Leu and [3H]Tdr. The beta-amyloids, on the other hand, did exert neurodegenerative effects on rat hippocampal cultured neurons in which ATP is mostly synthesized by the mitochondrion. The activities of beta 25-35 and [D-Ser26] beta 25-35 are dependent on their having beta-structures and not random forms. Although beta 25-35 was degraded rapidly by proteinase(s) in brain extract or leucine aminopeptidase, [D-Ser26] beta 25-35 is fairly resistant. These results indicate that one of the primary targets of beta-amyloids is suppression of mitochondrial succinate dehydrogenase, and the vulnerability of the brain of beta-amyloids can be explained by its large dependence on mitochondrial energy production. Moreover, racemization of serine residues of beta-amyloids may be involved in neurodegeneration and formation of senile plaques through escaping from the degradation process by brain proteinases.

Amino Acid Sequence↗

Hemostatic abnormalities in patients with pulmonary embolism compared with that in deep vein thrombosis.

We investigated hemostatic abnormalities in 37 patients with deep vein thrombosis (DVT) and pulmonary embolism (PE) (PE patients) and in 40 patients with DVT without PE (DVT patients). Plasma fibrinogen, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex, fibrin-D-dimer, activated protein C (APC)-protein C inhibitor (PCI) complex, von Willebrand factor (vWf), tissue plasminogen activator (t-PA), PA inhibitor-I (PAI-1), and thrombomodulin levels in both PE and DVT patients were significantly increased compared with normal volunteers. Plasma APC-PCI complex, PAI-1, and vWf levels in PE patients were significantly higher than those in DVT patients without PE. These findings indicate that PE patients are more hypercoagulable and hypofibrinolytic than DVT patients. Plasma TAT, APC-PCI complex, PAI-1, and vWf levels were the most sensitive indicators for PE. In these patients, increases in TAT and APC-PCI complex suggest DVT and increased PAI-1 and vWf suggest the risk of onset of PE.

Aged↗

Inhibition of restenosis by beraprost sodium (a prostaglandin I2 analogue) in the atherosclerotic rabbit artery after angioplasty.

We examined the effect of beraprost sodium (BPS), a stable prostaglandin I2 (PGI2) analogue, on restenosis after balloon angioplasty in the atherosclerotic artery in rabbits. Regional atherosclerosis was induced in the femoral artery of New Zealand white rabbits by balloon deendothelialization and 2% cholesterol diet. After establishment of atheroma in the femoral artery, angioplasty was performed. In all, 65 rabbits were assigned to the following six subcutaneous drug treatment groups: control group (n = 13, saline 0.25 ml/kg); BPS low-dose group (n = 11, BPS 50 micrograms/kg twice daily); BPS high-dose group (n = 12, BPS 100 micrograms/kg twice daily); 2-day BPS high-dose group (n = 11, BPS 100 micrograms/kg twice daily for 2 days after angioplasty); aspirin (ASA) group (n = 10, ASA 30 mg once daily); and BPS+ASA group (n = 8, BPS 50 micrograms/kg twice daily plus ASA 30 mg once daily). Administration of each drug was started 30 min before balloon angioplasty and was continued until 4 weeks thereafter, except in the 2-day BPS high-dose group. Re-examination 4 weeks after the angioplasty showed significant (p < 0.05) preservation of the luminal diameter in the BPS high-dose and 2-day BPS high-dose groups (1.30 +/- 0.15 and 1.25 +/- 0.09 mm, respectively) as compared with that in the control group (0.83 +/- 0.10 mm); however, the luminal diameter in the BPS low-dose, ASA, and BPS+ASA groups (0.94 +/- 0.18, 1.06 +/- 0.11, and 1.05 +/- 0.15 mm, respectively) was not significantly different from that in the control group.

Administration, Oral↗

Treatment of recurrent hypersomnia with methylcobalamin (vitamin B12): a case report.

A 32 year old male patient suffered from recurrent hypersomnia for 12 years was successfully treated with vitamin B12. Episodes of hypersomnia lasting a few days occurred repeatedly a few times each year. Furthermore, the frequency of episodes had increased during the last 2 years. During the administration of vitamin B12, the patient had no episodes of hypersomnia for 6 months. In addition, he did not have any episodes during a follow-up observation period of 17 months after cessation of the treatment. Thus, this case suggests that vitamin B12 may be effective for preventing recurrent hypersomnia.

Adult↗