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Biomedical subjects

T Kamada

Publications and source records attributed to T Kamada.

At least 343 records · Page 19Linked to original sources

Effect of transient forebrain ischemia on superoxide dismutases in gerbil hippocampus.

Substantial generation of oxygen-derived free radicals has been implicated in pathophysiology of ischemic brain damage. Immunoreactive mitochondrial manganese and cytosolic copper-zinc superoxide dismutases, initial and essential enzymes to scavenge superoxide radical anions, increased in the gerbil hippocampal neurons after transient forebrain ischemia. Neuronal cells responded to oxidative stress in ischemia and induced the protective mechanism to increase superoxide dismutases.

Animals↗

[A clinical and pathological study of non-Hodgkin's lymphoma of the nasal cavity and paranasal sinuses].

We studied 30 patients with early stage malignant lymphomas involving the nasal cavity and/or paranasal sinus who were treated between 1972 to 1991 in Hokkaido University Hospital. The mean age of the patients was 60.6 yr, and the male-to-female ratio was 2.6. The predominant histologic type was diffuse large cell type (n = 23). Treatment policy differed depending on time: radiotherapy (RT) alone between 1972 and 1980 (n = 15), RT followed by modified CVP or CHOP between 1981 and 1988 (n = 10) and BACOP followed by RT between 1989 and 1991 (n = 5). Overall five-year survival was 53%. Better survival was observed in patients with B-cell type (72%), smaller mass (tumor limited to the unilateral nasal cavity or paranasal sinus) (76%), and patients who were treated with combination chemotherapy (BACOP) followed by RT (100%). Eleven patients experienced recurrence. Four of nine local recurrences were in patients with T-cell lymphoma. CNS relapse was observed in three patients with T-cell lymphoma. We conclude that T-cell lymphoma arising at the nasal cavity and/or paranasal sinus needs careful follow-up for its high frequency of local and CNS relapse. More intensive treatment such as prophylactic whole brain RT, intrathecal administration of MTX or third generation chemotherapy (e.g. MACOP-B) might improve survival in these patients.

Adolescent↗

Induced resistance and susceptibility to cerebral ischemia in gerbil hippocampal neurons by prolonged but mild hypoperfusion.

Brief periods of non-lethal cerebral ischemia can induce resistance against subsequent lethal ischemia. In this study, asymptomatic gerbils after unilateral carotid artery ligation were subjected to 5 min of forebrain ischemia. The prolonged but mild hypoperfusion, by carotid occlusion, induced susceptibility at 1 day and tolerance at 30 days to lethal ischemia in the hippocampal neurons. The neuroprotective effect correlated well with induction of heat shock protein 72 in the hippocampal neurons. These results suggested that neuronal cells possess a cellular response to sublethal hypoperfusion and can survive forthcoming ischemic stress.

Animals↗

Rapid screening method of abnormal insulin-receptor gene expression: allele-specific oligonucleotide hybridization by using silent polymorphisms.

An asymmetrical reduction in the levels of the insulin receptor mRNA transcribed from one allele was reported in some patients with severe insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM). To detect this abnormality, we designed the less laborious method; Allele-specific oligonucleotide hybridization of the amplified mRNA (cDNA) by using silent polymorphisms in the insulin receptor gene (nucleotide positions at 1686 and 1698). The allelic frequencies of C-1686 and T-1686 were 0.63 and 0.37, respectively (0.60 and 0.40 in 10 normal subjects, and 0.67 and 0.33 in 20 NIDDMs; n.s.). Similarly, the allelic frequencies of A-1698 and G-1698 were 0.47 and 0.53, respectively (0.50 and 0.50 in the normal subjects, and 0.45, and 0.55 in the NIDDMs; n.s.). These results suggest that these two polymorphisms are very common in Japanese. Nineteen (64%) out of 30 cases are heterozygous at one or two position(s), suggesting that it is possible to distinguish the mRNA transcribed from each of two alleles of the insulin receptor gene with using allele-specific oligonucleotide hybridization. Although we successfully measured the ratio of mRNA expression from two alleles of the gene in 20 NIDDMs, there was no patient whose mRNA transcribed from one allele of the insulin receptor gene was extremely decreased. We showed that allele-specific oligonucleotide hybridization method is useful for the screening of abnormal insulin-receptor gene expression.

Alleles↗

Importance of left ventricular minimal pressure as a determinant of transmitral flow velocity pattern in the presence of left ventricular systolic dysfunction.

OBJECTIVES: This study was designed to assess whether the transmitral flow velocity pattern provides an estimation of left atrial pressure irrespective of the presence of left ventricular systolic dysfunction and, if not, to clarify the mechanism. BACKGROUND: The pulsed Doppler transmitral flow velocity pattern, particularly peak early diastolic filling velocity, has been shown to change in parallel with left atrial pressure. However, extremely elevated left atrial pressure in association with heart failure does not necessarily cause an increase in peak early diastolic filling velocity in patients. METHODS: Left atrial pressure was elevated with intravenous saline infusion in 11 dogs (normal left ventricular function group) and hemodynamic, transesophageal Doppler echocardiographic and M-mode echocardiographic variables were recorded at three different loading levels. In another 12 dogs, left atrial pressure was elevated by production of left ventricular systolic dysfunction with the stepwise injection of microspheres into the left coronary artery (left ventricular dysfunction group) and the same set of recordings was obtained at three different levels of dysfunction. RESULTS: Peak early diastolic filling velocity increased with left atrial pressure in the normal left ventricular function group and correlated with mean left atrial pressure (r = 0.61, p < 0.01) and early diastolic left atrial to left ventricular crossover pressure (r = 0.71, p < 0.01). In contrast, peak early diastolic filling velocity did not increase with left atrial pressure in the left ventricular dysfunction group and did not correlate with mean left atrial pressure (r = -0.05) or the crossover pressure (r = 0.06). Peak early diastolic filling velocity correlated well with the difference between the crossover pressure and left ventricular minimal pressure in the left ventricular dysfunction group (r = 0.64, p < 0.01). In contrast to peak early diastolic filling velocity, deceleration time of the early diastolic filling wave correlated with mean left atrial pressure and the crossover pressure irrespective of the primary cause of preload alteration (r = -0.54, r = -0.59, p < 0.01 respectively, n = 69 for all data). CONCLUSIONS: Preload dependency of the Doppler transmitral flow velocity pattern is hampered if an increase in left atrial pressure is due to left ventricular systolic dysfunction. In this setting, the increase in left ventricular minimal pressure due to left ventricular systolic dysfunction cancels the effect of the increase in left atrial pressure on the flow velocity pattern.

Animals↗

An AP-1 enhancer mediates TPA-induced transcriptional activation of the chicken insulin-like growth factor I gene.

As a step to elucidate a role of protein kinase C(PKC) pathways in the regulation of insulin-like growth factor I(IGF-I) gene, we sought to determine whether the IGF-I gene promoter of chicken can be a target of regulation by PKC. An initial gene transfer study showed that, in a human cell line HepG2, the IGF-I gene promoter directs accurate transcription of IGF-I-luciferase fusion gene and enhances luciferase activity. Treatment of transfected cells with 12-o-tetradecanoylphorbol 13-acetate(TPA) increased promoter activity of 2100 and 600bp 5'-flanking sequence 4.9- and 3.6-fold, respectively. Site-directed mutagenesis in the AP-1-like sequence located within the 600bp resulted in 91% loss of its TPA-induced promoter activity, and a gel mobility-shift analysis revealed that TPA-stimulation of HepG2 cells caused a dramatic increase in specific protein-binding to the AP-1-like sequence, suggesting that the sequence functions as an AP-1 enhancer. These observations support a direct role for PKC pathways in activating the IGF-I gene promoter in chicken.

Animals↗

Expression of the c-met/hepatocyte growth factor receptor gene during rat liver regeneration induced by carbon tetrachloride.

The hepatocyte growth factor is closely related to liver regeneration. And the c-met protooncogene is reported to encode a hepatocyte growth factor receptor. Little is known, however, about how the c-met gene is activated during liver regeneration. In this study, we demonstrated that expression of the c-met gene/hepatocyte growth factor gene was enhanced, with a distinct peak, following carbon tetrachloride administration, i.e., the gene expression was activated at 6 hours after the treatment, then decreased, and again increased. The present study suggested that this gene could be responding to liver regeneration and that the hepatocyte growth factor receptor plays an important role in regulating cell cycle progression prior to elevation of deoxynucleic acid synthesis during liver regeneration.

Animals↗

Quantitation of hepatitis C virus RNA in serum of asymptomatic blood donors and patients with type C chronic liver disease.

We describe a method for quantifying hepatitis C virus RNA in serum. This competitive assay combines reverse transcription and polymerase chain reaction and is based on coamplification of the target RNA with known amounts of synthetic mutated RNA. We tested serum samples from 104 hepatitis C virus carriers (9 asymptomatic blood donors and 95 patients with type C chronic liver disease) to determine the relationship between the replicative level of hepatitis C virus and various stages of the carrier states. The amount of circulating hepatitis C virus RNA ranged from 10(4) to 10(9.5) genomes/ml serum. The titer of hepatitis C virus RNA (logarithmic transformed copy numbers of RNA per milliliter of serum) was lower in asymptomatic blood donors (5.4 +/- 2.0) and in patients with chronic persistent hepatitis (7.3 +/- 1.1) than in patients with chronic active hepatitis (7.9 +/- 0.8), cirrhosis (7.8 +/- 0.7) or hepatocellular carcinoma (7.9 +/- 0.7). The titer of hepatitis C virus RNA was significantly lower in carriers younger than 40 yr old and correlated positively with the logarithmic transformed serum ALT level. Logistic regression showed that age and titer of hepatitis C virus RNA correlated independently with the stages of liver disease. These results showed that the replicative level of hepatitis C virus is higher in advanced liver disease and that elevation of viral replication may play an important role in liver injury and progression of liver disease. This competitive assay is useful in evaluating the state of viral replication in hepatitis C virus infection.

Alanine Transaminase↗

Bioactive glass promoted formation of nodules in periodontal-ligament fibroblasts in vitro.

The effects of bioactive glass and vitamin D3 on cultured fibroblasts derived from periodontal-ligament, with respect to their proliferation and alkaline-phosphatase activity were studied. The cells were cultured with or without the bioactive glass and/or vitamin D3, then the number and alkaline-phosphatase activity of the cells were measured periodically until the 33rd day. Formation of mineralized deposits was assessed by staining with alizarin red and von Kossa staining techniques. Fewer fibroblasts grew when they were cultured in the presence of bioactive glass and/or vitamin D3 as compared to those cultures without them. Alkaline-phosphatase activity was greater in the fibroblasts cultured with bioactive glass and vitamin D3 than in the cells grown without them. Mineralized deposits assessed by alizarin red and von Kossa staining techniques were observed microscopically around the fibroblasts cultured with bioactive glass and/or vitamin D3. A nodule visible after drying was evident only when both bioactive glass and vitamin D3 were present in culture. The results showed that although the bioactive glass and vitamin D3 decreased cell proliferation, they increased the alkaline-phosphatase activity of the fibroblasts which formed a nodule, suggesting an effect which might be useful for implant materials.

Alkaline Phosphatase↗

Low prevalence of hepatitis C virus antibodies in chronic liver disease in northwest China.

To evaluate the prevalence of hepatitis C virus infection in northwest China, 179 chronic liver disease patients in this area were examined for antibody to hepatitis C virus core protein (anti-HCVcore). This antibody was found in only 5 (14 percent) of 37 chronic non-A, non-B liver disease patients, in 11 (16%) of 67 asymptomatic hepatitis B virus carriers, and in 20 (27%) of 75 chronic hepatitis B patients. High titers of anti-HCVcore (cut off index > 2) were observed in 3 (60%), 5 (45%), and 9 (45%) of the anti-HCVcore-positive cases of these groups, respectively. We further investigated the seroprevalence of antibodies to hepatitis B virus in the 37 chronic non-A, non-B liver disease patients. All 5 anti-HCVcore-positive cases were positive for a hepatitis B virus marker, with only 44% (14/32) of the anti-HCVcore-negative patients (P < 0.05). Based on these findings, it is concluded that the prevalence of hepatitis C virus infection in chronic non-A, non-B liver disease is unexpectedly low in northwest China and that hepatitis B and C viruses seem to have a similar mode of infection in that area.

Adult↗

Usefulness of anaerobic threshold for evaluating daily life activity and prescribing exercise to the healthy subjects and patients.

Forty-three subjects were studied as for the relationship between anaerobic threshold (AT) and medical data including individual life style. Age, habit of exercise, and obesity are related to AT, showing a correlation coefficient of 0.533, 0.457 and 0.428, respectively. On the other hand, plasma lipid levels and alcohol are not so strongly related to AT, showing low correlation coefficient of 0.241 and 0.209 respectively. No correlation is found on the other factors such as FBS, Liver and blood pressure etc. Physical active life, commuting time, cumulative exercise hours in a month and work hours in a month are correlated to AT, showing correlation coefficient of 0.799, 0.734, 0.708 and 0.671, respectively, and even "more than once a month" frequency of exercise has affected AT. In conclusion, AT is a useful index for evaluating daily life activity and prescribing exercise regimen.

Activities of Daily Living↗

Clinical evaluation of plasma des-gamma-carboxy prothrombin as a marker protein of hepatocellular carcinoma in patients with tumors of various sizes.

We measured des-gamma-carboxyprothrombin (DCP) (prothrombin induced by vitamin K absence or antagonist-II, abbreviated as PIVKA-II) by a newly developed enzyme immunoassay using an anti-DCP monoclonal antibody in 665 human subjects, of which 112 were patients with hepatocellular carcinoma (HCC). PIVKA-II was elevated to more than 0.1 AU/ml in 54 of the 112 patients (48.2%) with HCC, while it was positive only in 7.1% of those with liver cirrhosis and 3.1% of those with chronic hepatitis. Three patients with elevated PIVKA-II greater than 0.1 AU/ml who had been diagnosed as having liver cirrhosis by ultrasonography and computed tomography at the start of this study developed a diffuse type of HCC three or six months later, which was detected by angiography. No obvious correlation was observed between plasma PIVKA-II concentration and serum alpha-fetoprotein (AFP) level in HCC patients. Of the 112 HCC patients, 40.2% showed an increase in AFP to above 200 ng/ml. In the remaining patients, 32.8% had a PIVKA-II concentration greater than 0.1 AU/ml. In these patients with a negative or low serum AFP concentration, PIVKA-II proved to be a valuable tumor marker for laboratory diagnosis of HCC. Among them, 59.8% tested positive for PIVKA-II and/or AFP. Thus, combination assay with PIVKA-II and AFP seems useful for increasing the accuracy of laboratory diagnosis of HCC. None of patients with a solitary tumor smaller than 2 cm had elevated PIVKA-II. In patients with larger-sized and multiple HCC, positive results of elevated PIVKA-II were more frequent than those of increased AFP.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗

Brief myocardial ischemia affects free radical generating and scavenging systems in dogs.

This study examined whether brief repeated myocardial ischemia altered free radical generating and scavenging activity in a dog model. In dogs preconditioned with four 5-min left anterior descending coronary artery (LAD) occlusions and reperfusions, we examined transcardiac changes in both the function of neutrophils, cells which are major free radical generators, and in myocardial antioxidant enzyme activity, as an indication of free radical scavenging. Neutrophil function was assessed by determining luminol-enhanced whole blood chemiluminescence (CL) induced by zymosan. Blood was taken simultaneously from the carotid artery and the cardiac vein running along the occluded LAD. Preconditioning with sublethal ischemia significantly reduced whole blood CL in the cardiac vein compared with the carotid artery after the first and fourth 5-min reperfusions, while there was no difference in neutrophil count between these sampling sites. Immediately after brief repeated ischemia and reperfusion, manganese-superoxide dismutase (SOD) activity was significantly enhanced, and glutathione reductase activity was markedly reduced in the ischemic, compared with the non-ischemic, myocardium. There were no differences in the myocardial activities of copper, zinc-SOD, glutathione peroxidase, and glutathione S-transferase between the ischemic and non-ischemic regions. Also, no difference was observed between the reduced myocardial glutathione levels in these regions, although the oxidized glutathione level was significantly higher in the ischemic regions of the subepicardial and subendocardial areas. We demonstrated that brief repeated ischemia affects free radical generating and scavenging systems in the ischemic myocardium.

Animals↗

Effects of cytokines on HLA class I antigen expression on Huh6 and HB611 cells.

This study investigated the expression of HLA class I antigens on Huh6 and HB611 cells induced by interferon (IFN)-alpha, IFN-gamma, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta. All of these cytokines induced the antigens on both cells in a dose-dependent manner, with IFNs inducing much more expression than TNF-alpha or IL-1 beta. We have already reported that protein kinase C (PKC) is involved in the antigen expression induced by IFN-gamma on Huh6 cells. The antigen expression induced by IFN-alpha was also blocked by a PKC inhibitor, H-7. However, the antigen expression by TNF-alpha or IL-1 beta was not inhibited by H-7, by a protein kinase A inhibitor, HA1004, nor by a calmodulin antagonist, W-7. These results suggested that PKC, Ca(2+)-calmodulin, and cAMP are not involved in the induction of HLA class I antigens on both cells by TNF-alpha and IL-1 beta. We concluded that TNF-alpha and IL-1 beta induced much less expression of HLA class I antigens on both cells than IFNs and that this might be because the signaling pathway by TNF-alpha and IL-1 beta differed from that by IFNs.

Carcinoma, Hepatocellular↗