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Biomedical subjects

T Kanda

Publications and source records attributed to T Kanda.

At least 325 records · Page 18Linked to original sources

Comparative effects of linoleic acid and linoleic acid hydroperoxide on growth and morphology of bovine retinal pigment epithelial cells in vitro.

PURPOSE: Outer segments of the photoreceptor rods that are phagocytized by the retinal pigment epithelial (RPE) cells contain a high proportion of polyunsaturated fatty acids (PUFA). PUFA are susceptible to lipid peroxidation. We hypothesized that the resulting peroxides could injure RPE cells leading to retinal degeneration. Accordingly, we compared the effects of linoleic acid (LA) and its hydroperoxide (LHP) on the growth and morphology of RPE cells using laser scanning microscopy and transmission microscopy. METHODS: We counted the number of RPE cells after incubation for 24 and 48 hrs with concentrations of LA or LHP of 0.035, 0.175, and 0.35 mM. To observe the actin filaments, cultured RPE cells were stained with rhodamine phalloidin. The cells were prefixed with 2% glutaraldehyde and postfixed in 1% osmium tetroxide. Specimens were embedded in Epon 812 after dehydration, and the ultrathin sections were doubly stained with 2% uranyl acetate and 2% lead acetate for examination by transmission electron microscopy. RESULTS: Exposure to LA or LHP produced dose-dependent damage to RPE cells with a significantly greater effects of LHP than LA. After incubation for 24 hrs with 0.35 mM LA, the number of vacuoles in RPE cells exceeded that observed in control RPE cells by 365 nm laser microscopy. Exposure to 0.35 mM LHP for 24 hrs produced a pycnotic nucleus, with diffuse and granular autofluorescences observed in and around it. Exposure of RPE cells to 0.35 mM LA for 24 hrs showed that the LA incorporated into the lysosomes was digested and released extracellularly from lysosomes via exocytotic vesicles. However, such exposure to LHP damaged the RPE cells, including the membranes in the pinocytotic vesicles. The packed membranes resembled myelin. CONCLUSIONS: While the LA incorporated into the lysosomes was released extracellularly, LHP persisted in the RPE cells, being observed as autofluorescent lipofuscin-like materials. LHP was cytotoxic, and caused damage to the membranes of pinocytotic vesicles and lysosomes.

Animals↗

[Occurrence of ileus after voglibose treatment in an elderly diabetic patient with gait disturbance caused by cerebral hemorrhage].

Alpha-glucosidase inhibitor can suppress postprandial hyperglycemia by delaying the absorption of carbohydrates in the intestine, and may be useful in obese patients with non-insulin-dependent diabetes mellitus (NIDDM) and preserved insulin secretion. We encountered an obese elderly patient with NIDDM in whom gait disturbance had developed after cerebral hemorrhage and who suffered from ileus after treatment with voglibose. The patient had received voglibose which is reported to cause fewer abdominal symptoms than acarbose, for 15 days. The patient, a 63-year-old woman, was given a diagnosis of NIDDM in February 1995, and was treated with a sulfonylurea agent. However, her glycemic control remained poor and she was admitted to our hospital in April 1995. Her body mass index was 30.5 kg/m2 and laboratory investigation revealed a fasting plasma glucose level of 211 mg/dl, a postprandial (2 h) plasma glucose level of 288 mg/dl, HbAlc of 9.9%, a fasting insulin level of 9 microU/ml, urinary C-peptide excretion of 95.7 micrograms/ day, and an coefficient of variation of R-R value of 2.1%. Fifteen days after glibenclamide was replaced by to voglibose, abdominal pain, nausea, constipation, and ausculatory sounds of gurgling developed, and niveau were noted on an abdominal roentgenogram which indicated that simple ileus had developed. Voglibose was discontinued and the patient was treated with an enema and hot air. She recovered from simple ileus on the next day. This patient had had two abdominal surgeries and a cerebral hemorrhage, and her daily physical activities were limited, which might have contributed to ileus. In elderly patients with NIDDM, a history of abdominal surgery and the amount of daily exercise must be considered when deciding whether or not to give alpha-glucosidase inhibitors.

Cerebral Hemorrhage↗

["Vertigo" the fact analysis of clinical practice by ENT physicians of Chiba Prefecture by "send-out" questionnaires].

Despite the fact that vertigo has been one of the most frequent complaints encountered in daily practice in an ENT outpatient clinic, it is believed to be the most unwelcome subject for ENT physicians. The reasons are diverse; e.g., the understanding of vertigo is still a difficult task for most physicians and requires time-consuming multiple studies. However, answers to those questions, although speculated a posteriori, are yet to be substantiated. Therefore, we have analyzed the data obtained from multiple questionnaires that were addressed to ENT physicians practicing in Chiba Prefecture in November of 1993. However, those who work in publicly run hospitals were excluded from the study. The study included otorhinolaryngologists who were members of the Society of Otorhinolaryngology of Japan. We received filled questionnaire forms from 76 of 155 members (49%). The age ranged from 33 to 82 years (mean 55.8 years, 68 men and 8 women). From these questionnaires, it became apparent that physicians are not necessarily reluctant to see patients with vertigo. Instead, most ENT physicians appeared to be actively paying attention to this symptom and to be making efforts to approach its diagnosis and treatment. Although we are not certain if the data obtained here represent the majority of ENT physicians, the positive attitudes toward the patients with vertigo/dizziness would certainly encourage those of us who are interested in this particular symptom category.

Adult↗

Beneficial effect of amiloride, A Na(+)-H+ exchange blocker, in a murine model of dilated cardiomyopathy.

We investigated the effect of amiloride, a Na(+)-H+ exchange blocker, on ventricular hypertrophy in a murine model of dilated cardiomyopathy (DCM). Mice with DCM were given orally amiloride for 60 days. The ratio of heart weight to body weight and left ventricular cavity dimension were significantly smaller in both amiloride groups than those in furosemide and control (untreated DCM) groups (p < 0.05). The fiber diameter was significantly smaller in amiloride groups than that in furosemide group (p < 0.01). Plasma and cardiac angiotensin II (AII) levels were decreased in amiloride-treated groups compared with those in furosemide or control group (p < 0.05). Our findings suggest that amiloride prevents the development of myocardial hypertrophy and left ventricular dilatation in DCM in association with a reduction of AII.

Amiloride↗

Are glomerular lesions alternatives to microalbuminuria in predicting later progression of diabetic nephropathy?

We inquired whether the type of diabetic glomerulosclerosis, diffuse or nodular, is of value as an alternative to microalbuminuria in predicting later progression of renal disease. To answer this question, we conducted a retrospective cohort study in eleven Japanese non-insulin-dependent diabetes mellitus patients with normo- to microalbuminuria. Nodular diabetic glomerulosclerosis was found in six patients, and diffuse diabetic glomerulosclerosis in five patients. The mean follow-up period was 41.5 months (range 12-65). Three patients developed persistent proteinuria and one developed chronic renal failure. Mean level of serum creatinine in all patients was elevated from 0.97 +/- 0.23 mg/dl (SD) to 1.10 +/- 0.37 mg/dl (P = 0.098). The rate of increase in serum creatinine was 0.068 +/- 0.115 mg/dl/year in nodular diabetic glomerulosclerosis, and 0.023 +/- 0.069 mg/dl/year in a diffuse one. No difference was found between these two types of diabetic glomerulosclerosis (P = 0.445). We conclude that in normo- to microalbuminuria diabetic nephropathy the type of diabetic glomerulosclerosis, diffuse or nodular, is not necessarily an alternative to microalbuminuria in predicting its later progression in Japanese non-insulin-dependent diabetes mellitus patients.

Albuminuria↗

Amlodipine inhibits the development of right ventricular hypertrophy and medial thickening of pulmonary arteries in a rat model of pulmonary hypertension.

This study was designed to evaluate the effects of amlodipine, a new calcium channel blocker, on the development of right ventricular hypertrophy and thickening of the media of the pulmonary arteries in a rat model of pulmonary hypertension. Pulmonary hypertension was induced in rats by administering a single injection of monocrotaline, 80 mg/kg. The oral administration of amlodipine, 3, 10, or 30 mg/kg/day, was initiated 24 hours later (day 1). On day 28 of therapy, we determined the right ventricular systolic pressure (RVSP), the mass ratio of the right ventricle (RV) to the left ventricle, the thickness of the wall of the RV, the diameter of myocardial fibers in the RV, the percent thickness of the media of the pulmonary artery, and the percent area of smooth muscle in the pulmonary arteries. The magnitude of all parameters was significantly less in the rats administered amlodipine, 30 mg/kg/day, vs. the control group given monocrotaline alone. RVSP, the percent medial thickness, and the percent smooth muscle area, were significantly lower in rats administered a dose of amlodipine, 30 mg/kg/day vs. 10 mg/kg/day. The oral administration of amlodipine, 30 mg/kg/day, inhibited the development of RV hypertrophy and medial thickening of the pulmonary arteries in rats exposed to monocrotaline significantly more effectively vs. the untreated control exposed only to monocrotaline.

Amlodipine↗

Correlation between serum level of, and tissue positivity for, alpha-fetoprotein in hepatocellular carcinoma.

The serum level of alpha-fetoprotein (AFP) is a marker for primary liver tumors. To evaluate the relationship between the serum level of AFP and the positivity of liver tissue for this marker, specimens of liver were obtained at autopsy from patients with hepatocellular carcinoma (HCC). Tissues were fixed with formalin or Kryofix and immunostained for AFP. Serum AFP titer at autopsy was positively correlated with AFP staining in tissue fixed by Kryofix and stained with monoclonal antibody against AFP. The correlation was significant for plasma levels of AFP above 5,000 ng/ml. Results suggest that elevated serum AFP levels are an indicator of the progression of HCC.

Aged↗

An autopsy case of malignant lymphoma with a high serum CA 125 level occurring only in the brain and pericardium.

We report an autopsy case of a central nervous system (CNS) B-cell type lymphoma followed by cardiac tamponade. In this case, lymphoma cells which occurred primarily in the pericardium appear to metastasize to the brain and gradually increase in size in spite of control of the CNS lesion. The serum carbohydrate antigen 125 (CA 125) level was highly elevated and the autopsy findings showed the involvement of lymphoma only in the pericardium rather than the CNS, and the pericardium, not the tumor cells, was immunohistochemically positive for CA 125. Through this rare case, two things are suggested: first, the serum CA 125 level is elevated when B-cell type lymphoma infiltrates the coelomic epithelium; second, CA 125 is overproduced and secreted by the pericardium but not the lymphoma cells. Measurement of the serum CA 125 level may become a diagnostic marker for the infiltration of malignant lymphoma in the coelomic epithelium such as the pericardium, peritoneum or pleura.

Aged↗

Lutembacher's syndrome complicated by jaundice.

We encountered a 78-year-old female with jaundice induced by Lutembacher's syndrome, which, to our knowledge, is the first such case to be reported. Laboratory data and ultrasonographic examination revealed liver congestion with dilatation of the inferior vena cava and hepatic veins. A large atrial septal defect was found using two-dimensional echocardiography; the mitral valve area measured 1.6 cm2 by planimeter. Clinicians should be aware of congenital heart disease as an underlying cause of jaundice.

Aged↗

Artemether-pyrimethamine in the treatment of pyrimethamine-resistant falciparum malaria.

In vitro susceptibility and clinical response of multidrug resistant Plasmodium falciparum to the combination artemether-pyrimethamine were evaluated in patients with acute uncomplicated falciparum malaria. Sixty patients were randomized to receive 3 oral regimens of the combination artemether-pyrimethamine as follows: Regimen-I: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then placebo on the two consecutive days; Regimen-II: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then artemether (150 mg) plus pyrimethamine (50 mg) on the second day, and placebo on the third day; Regimen-III: artemether (300 mg) plus pyrimethamine (100 mg) on the first day, then artemether (150 mg) plus pyrimethamine (50 mg) on the second and third days. All patients had a rapid initial response to treatments with 95% of parasitemia being cleared within the first 24 hours. PCT24hours and PCT48hours were similar among the three drug regimens (11 vs 4, 6 vs 12, and 9 vs 11 patients for a 1-day, 2-day, and 3-day combination regimen, respectively). Fever was cleared within 48 hours in all patients in either group. Transient mild nausea, vomiting and loss of appetite were found in a few patients during the first 2 days of treatment. Seven patients did not complete the 28 day follow-up period (5 vs 2 in a 1-day vs 2-day regimen), the reason for withdrawal was not associated with drug-related adverse effects. Only 53 patients were therefore qualified for the efficacy assessment. There was 15, 13 and 5 patients in a 1-day, 2-day and 3-day combination regimens, respectively, who had reappearance of the parasitemia between days 11 and 21. The cure rates of the 3 treatment groups were statistically significantly different (0, 27.8, and 75% for a 1-day, 2-day and 3-day combination regimen, respectively). Two patients developed P. vivax malaria on days 20 and 24. All of the isolates were highly resistant to pyrimethamine, with MIC of 10(-5) M. There is potential advantage of this combination therapy in reducing the dosage and treatment period of artemisinin derivative, which is therefore likely to improve complaince in clinical practice. The use of a 3-day combination regimen (300 mg artemether plus 100 mg pyrimethamine on the first day, then 150 mg artemether plus 50 mg pyrimethamine on the second and third days) seems to be a good alternative regimen to sulfadoxine/ pyrimethamine in areas where P. falciparum is sensitive to pyrimethamine eg in Africa.

Adolescent↗

[Clinical evaluation of sulbactam/cefoperazone for lower respiratory tract infections. Correlation between the efficacy of sulbactam/cefoperazone and beta-lactamase].

The efficacy and safety of sulbactam/cefoperazone (SBT/CPZ) were evaluated in 42 patients with respiratory tract infections, including pneumonia (29 patients) and lower respiratory tract infections (5 patients). Overall clinical efficacy rates (excellent + good) were 79% in pneumonia and 80% in respiratory tract infections in 34 patients evaluated for clinical efficacy. It was excellent that the clinical efficacy rate was 92% in mild and moderate pneumonia. Pathogens isolated from sputa were 31 strains, including 8 strains of Pseudomonas aeruginosa, 7 of Streptococcus pneumoniae, 3 of Staphylococcus aureus and 3 of Haemophilus influenzae. Since the isolates were eradicated in 18 strains, replaced in 3, unchanged in 2 and unknown in 8, the overall eradication rate was 91%. The eradication rates were 89% in beta-lactamase producing strains and 100% in beta-lactamase positive sputum, and excellent or good in 19 (83%) of 23 patients with beta-lactamase negative sputum. The eradication rate was 88% in 5 patients with beta-lactamase positive sputum. One patient experienced a moderate rash. Abnormal laboratory test values were observed in 10 patients (26.3%), but these abnormalities were mild and transient. These results suggested that SBT/CPZ was effective and safe for the treatment of respiratory tract infections caused by beta-lactamase producing as well as beta-lactamase non-producing bacteria.

Aged↗

Activity of artemether-azithromycin versus artemether-doxycycline in the treatment of multiple drug resistant falciparum malaria.

The efficacy of the combination of artemether with doxycycline or azithromycin was evaluated in 60 patients with acute uncomplicated falciparum malaria who attended malaria clinic in Mae Sot, Tak Province (Thai-Myanmar border). Patients (30 each) were randomized to receive (a) 300 mg artemether together with 100 mg doxycycline as initial doses, followed by 100 mg artemether plus 100 mg doxycycline at 12 hours later, then 100 mg doxycycline every 12 hours for another 4 days, or (b) 300 mg artemether together with 500 mg azithromycin, followed by 250 mg azithromycin at 24 and 48 hours. The follow-up period was 28 days. Patients in either group had a rapid initial response to treatment with comparable PCT and FCT. The cure rate of artemether-azithromycin regimen was significantly lower than that of artemether-doxycycline regimen (14.8 vs 53.3%). Low cure rate from artemether-azithromycin combination in this study was likely to be due to inadequate azithromycin dosage. However, with the low incidence of gastrointestinal adverse effects, the once daily dose of azithromycin could still be increased in order to enhance its clinical efficacy. The simplicity of drug administration and lesser incidence of adverse effects make azithromycin a more proper partner of artemether than doxycycline. Further dose-finding and pharmacokinetic study with the artemether-azithromycin combination is encouraging.

Adolescent↗

Tissue-specific regulation of the expression of rat intestinal bile acid-binding protein.

A lipid-binding protein identical to the rat intestinal bile acid-binding protein, termed I-15P, was expressed in steroid hormone-producing tissues such as ovary and adrenal gland, but not testis. In immature rats, I-15P was expressed in intestine but not in ovaries. The expression of I-15P in the ovaries of immature rats was induced to the level in immature rats by gonadotropin treatment. This suggests that the expression of I-15P in the ovaries is controlled by the ovarian cycle. The present results indicate that the expression of I-15P is developmentally and hormonally controlled in a tissue-specific manner.

Adrenal Glands↗

Molecular cloning, expression, and characterization of a human intestinal 15-kDa protein.

We have isolated a cDNA encoding a human intestinal 15-kDa protein (I-15P) from a human ileal lambda gt 11 cDNA library, using a full-length rat I-15P cDNA. One clone encompassed 571 nucleotides and encoded a 128-amino-acid protein with a calculated molecular mass of 14355 Da. The deduced amino acid sequence of human I-15P showed high similarity to the rat counterpart (78%), mouse ileal lipid-binding protein (80%) and porcine gastrotropin (75%). It also exhibited 36% similarity to human liver fatty-acid-binding protein (L-FABP). Northern blot analysis of human I-15P revealed a single transcript only in ileum, however, the reverse-transcription/PCR demonstrated expression in ovary and placenta, but it was much lower than in ileum. Transformation of Escherichia coli with the I-15P cDNA resulted in the efficient expression of a protein that was identical to the ileal cytosolic I-15P. In vitro binding studies revealed that the bacterially expressed recombinant I-15P showed much lower affinities for palmitate and oleate than L-FABP. However, it showed similar affinity for taurocholate, compared with a control, BSA. Comparison of the structural features of human I-15P and human L-FABP suggested that loss of a long alpha-helix region and hydrophobic profile of I-15P may be attributable to a unique ligand-binding specificity of I-15P.

Aged↗

Mutational analysis of human papillomavirus type 16 E6 protein: transforming function for human cells and degradation of p53 in vitro.

The E6 oncoprotein of human papillomavirus type 16 (HPV 16) [151amino acids (AA) long] contains four metal-binding motifs, C-X-X-C, and is postulated to form two 29-AA finger-like structures in the N-terminal and C-terminal halves, which mediate degradation of p53 and binding to p53, respectively. We constructed a series of E6 mutants with single-AA substitutions in these finger regions (AAs 34-62 and 107-135) and examined their transforming function for human embryonic kidney (HEK) cells in conjunction with HPV 16 E7 and their interaction with human p53 in vitro. The mutants with substitution of L for F-37, G for L-50, S for Y-54, and P for L-110, which did not transform HEK cells, showed markedly lowered activity to direct degradation of p53. The mutants with substitutions of G for R-39, G for V-42, G for Y-43, L for F-47, and G for V-53 lost the transforming function, but they could mediate degradation of p53 at levels comparable to the activities of the wild-type and transforming mutants. Like the wild type, all of the E6 mutants were localized by immunofluorescence to the nuclei of human TS21B cells or monkey COS-1 cells, except for the E6 mutant with substitution of G for Y-43 whose expression was undetectable. The levels of E6 mutants metabolically labeled in COS-1 cells were comparable to those of the transforming E6s. The data indicate that E6-directed degradation of p53 is necessary but not sufficient for HPV 16-mediated transformation of of HEK cells.

Amino Acid Sequence↗

Glycosphingolipid composition of murine neuroblastoma cells: O-acetylesterase gene downregulates the expression of O-acetylated GD3.

We have studied the glycosphingolipid composition in an F-11 neuroblastoma cell line originated from hybridization of a mouse neuroblastoma cell line (N18TG-2) with rat dorsal root ganglion cells. The total lipid-bound glucose of F-11 cells was estimated to be 0.28 micrograms/mg of protein and the total lipid-bound sialic acid was 0.82 micrograms/mg of protein. The major neutral glycosphingolipids were Gb4 (37% of the total neutral glycosphingolipids), Gb3 (15%), LacCer (21%), and GlcCer (15%). The major gangliosides were found to be GM3 (37% of the total gangliosides), GD3 (27%), O-acetylated GD3 (18%), and GD1a (4%), with trace amounts of GD2. The unusually high concentration of O-acetylated GD3 is consistent with its putative role as a tumor marker. Immunocytochemical localization studies of GD3 and O-acetylated GD3, examined by mouse monoclonal antibodies R24 and D1.1, respectively, revealed that the cell bodies and processes were all positively stained. To elucidate the role of O-acetylated GD3 in tumorigenesis, we transfected F-11 cells with the O-acetylesterase gene from influenza C virus. Compared with the original cell line, the transfected cells showed a dramatic increase in the level of GD3 (150% of that in the control cells) and a significant decrease of the concentration of O-acetylated GD3 (27% of control cells). In addition, the transfected F-11 cells exhibited a morphology different from the parental cells with enlarged cell bodies and elongated neurites. We conclude that alteration of ganglioside composition, particularly the expression of GD3 and O-acetylated GD3, may be associated with the morphological changes observed in this cell line.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗

Interleukin 1 beta up-regulates the expression of sulfoglucuronosyl paragloboside, a ligand for L-selectin, in brain microvascular endothelial cells.

Treatment of cultured bovine brain microvascular endothelial cells (BMECs) with interleukin 1 beta (IL-1 beta), an inflammatory cytokine, was shown to induce the accumulation of sulfoglucuronosyl paragloboside (SGPG), a glycolipid bearing the HNK-1 epitope. This resulted in the attachment of a greater number of human lymphocytes to the treated than to the untreated BMEC monolayers. Attachment of human lymphocytes to the IL-1 beta-activated BMEC cells could be blocked either by incubation of the human lymphocytes with an anti-L-selectin antibody or by application of an anti-SGPG antibody to the BMECs. These results suggest that SGPG may act as an important ligand for L-selectin for the regulation of the attachment of activated lymphocytes and their subsequent invasion into the nervous system parenchyma in inflammatory disorders of the central and peripheral nervous systems.

Animals↗