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Biomedical subjects

I Kato

Publications and source records attributed to I Kato.

At least 91 records · Page 5Linked to original sources

Efficient retrovirus-mediated transfer of the multidrug resistance 1 gene into autologous human long-term repopulating hematopoietic stem cells.

Pre-clinical studies indicate that efficient retrovirus-mediated gene transfer into hematopoietic stem cells and progenitor cells can be achieved by co-localizing retroviral particles and target cells on specific adhesion domains of fibronectin. In this pilot study, we used this technique to transfer the human multidrug resistance 1 gene into stem and progenitor cells of patients with germ cell tumors undergoing autologous transplantation. There was efficient gene transfer into stem and progenitor cells in the presence of recombinant fibronectin fragment CH-296. The infusion of these cells was associated with no harmful effects and led to prompt hematopoietic recovery. There was in vivo vector expression, but it may have been limited by the high rate of aberrant splicing of the multidrug resistance 1 gene in the vector. Gene marking has persisted more than a year at levels higher than previously reported in humans.

Adolescent↗

Diet, smoking and anthropometric indices and postmenopausal bone fractures: a prospective study.

OBJECTIVE: Bone fractures are an important cause of morbidity and mortality among the elderly in the US. The present study assesses the possible role of a number of risk factors for postmenopausal bone fractures. METHODS: We analysed the relationships of anthropometric, demographic and lifestyle factors with the risk of bone fracture among 6250 postmenopausal women in a prospective cohort study, the New York University Women's Health Study. RESULTS: After an average of 7.6 years of follow-up, 1025 new incident bone fractures were reported, including 34 hip and 159 wrist fractures (incidence rates; 71.6 and 334.7 per 105 woman-years, respectively). The risk of fracture increased with increasing age, body height and total fat intake, while it was significantly lower among obese and African American women. The relative risk among African Americans was 0.45 (95% CI: 0.32-0.63) compared with non-African Americans. Women taller than 170 cm had a 64% increase in risk of fractures, as compared with those under 155 cm. These associations were generally more pronounced when fractures were limited to those at the hip and wrist. CONCLUSIONS: The present study provides an indication for a potential role of dietary fat in the development of postmenopausal fractures and further evidence to support protective effects of obesity, short stature and African American ethnicity.

Adult↗

Inducible differentiation and apoptosis of the pre-B cell receptor-positive pre-B cell line.

The function of the pre-B cell receptor (pre-BCR) during B cell differentiation is not precisely defined. To investigate the pre-BCR receptor activity, we have established pre-BCR-positive pre-B cell lines that are able to differentiate into immature B cells in vitro. Antibody cross-linking of the pre-BCR induced apoptosis and differentiation accompanied with tyrosine phosphorylation. A specific tyrosine-phosphorylated 43 kDa protein (p43) was found down-stream of the pre-BCR. The results demonstrated the receptor function of pre-BCR, which indicates that a ligand-like molecule or a cross-linking structure on the cell surface is possibly present.

Animals↗

Psychotropic medication use and risk of hormone-related cancers: the New York University Women's Health Study.

BACKGROUND: The use of psychotropic medications may increase the risk of hormone-related cancers in females through increased gonadotropin secretion, but the data from epidemiologic studies are limited to evaluate the hypothesis. METHODS: The association between the use of psychotropic medications and cancer incidence was studied in a prospective cohort study that involves 15,270 women who participated in mammographic screening. The relative risks (RR) and 95 per cent confidence intervals (CIs) for cancer associated with the use of psychotropic medications were estimated by the Cox's proportional hazard model. RESULTS: During an average of 7.3 years of follow-up, 1,130 incident cases of cancer were identified, including 566 breast, 67 endometrial and 47 ovarian cancers. The use of any type of psychotropic medication at baseline was associated with increased risks of breast [relative risk (RR) = 1.39, 95 per cent CI 1.11-1.74], endometrial (RR=1.71; 95 per cent CI 0.93-3.14) and ovarian (RR= 1.48, 95 per cent CI 0.69-3.16) cancers, whereas no increase in risk was observed for other cancers (RR = 1.06). When the subjects were divided by menopausal status at baseline, premenopausal women tended to have higher risk of all hormone-related cancers (RR = 1.73, 95 per cent CI 1.27-2.35) than postmenopausal women (RR=1.23, 95 per cent CI 0.94-1.62). The magnitude of the RR associated with the use of these medications did not change by length of follow-up. Analysis by type of medication did not find that the association was limited to specific types. CONCLUSION: The observed association needs to be confirmed in further studies based on more detailed medication history.

Adult↗

Cervical curvature after laminoplasty for spondylotic myelopathy--involvement of yellow ligament, semispinalis cervicis muscle, and nuchal ligament.

To assess the consequences of cervical laminoplasty on postoperative lordosis, a retrospective radiographic analysis of 31 patients undergoing laminoplasty for spondylotic myelopathy was completed. Special attention was paid to lordotic changes occurring at each level over more than 2 years. Preoperative lordosis remained unchanged with the patients wearing a cervical orthosis 1 week postoperatively. However the lordosis subsequently demonstrated a significant decrease in 87% of patients over an average of 3.1 years. Lordotic alignment at C2-C3 and C6-C7 before surgery significantly decreased in 81% and 58% of patients 1 week postoperatively, and 84% and 81% at last follow up, respectively, while lordotic alignment at other levels pre- and postoperatively did not significantly change. Loss of lordotic alignment was largely attributed to detachment of semispinalis cervicis muscle on C2 and nuchal ligament on C6/C7 with a posterior approach and/or section of yellow ligament at C2-C3.

Adult↗

Isolation of two novel genes, down-regulated in gastric cancer.

Using a differential display technique, we identified two genes that are down-regulated in human gastric cancer tissue as compared to normal gastric mucosa. The down-regulated expression of these genes in gastric cancer tissue was confirmed by northern blotting analysis and RT-PCR. One, CA11, was a novel gene expressed predominantly in the stomach and was depleted in all of the gastric cancer cell lines examined. The other gene, GC36, was homologous to the digestive tract-specific calpain gene, nCL-4. The expression of both GC36 and nCL-4 was suppressed or depleted in gastric cancer cell lines of differentiated and poorly differentiated types. This is the first report of genes, the expression of which is down-regulated with considerable frequency in gastric cancer.

Alternative Splicing↗

Roles of the AGE-RAGE system in vascular injury in diabetes.

This study concerns whether advanced glycation endproducts (AGE) are related to microvascular derangement in diabetes, exemplified by pericyte loss and angiogenesis in retinopathy and by mesangial expansion in nephropathy. AGE caused a decrease in viable pericytes cultivated from bovine retina. On the other hand, AGE stimulated the growth and tube formation of human microvascular endothelial cells (EC), this being mediated by autocrine vascular endothelial growth factor. In AGE-exposed rat mesangial cells, type IV collagen synthesis was induced. Those AGE actions were dependent on a cell surface receptor for AGE (RAGE), because they were abolished by RAGE antisense or ribozyme. The AGE-RAGE system may thus participate in the development of diabetic microangiopathy. This proposition was supported by experiments with animal models; several indices characteristic of retinopathy were correlated with circulating AGE levels in OLETF rats. The predisposition to nephropathy was augmented in RAGE transgenic mice when they became diabetic.

Animals↗

CD4(+)-T-Cell-mediated resistance to systemic murine candidiasis induced by a membrane fraction of Candida albicans.

We induced resistance to systemic Candida albicans infection through CD4(+)-cell-mediated immunity in mice by immunization with subcutaneous injections of live C. albicans cells emulsified in incomplete Freund adjuvant. Using the resistant mice, we tested subcellular fractions of C. albicans cells for antigenicity. The fractions were derived from digested surface cell walls, insoluble membranes, or soluble and insoluble cytoplasmic materials, which were prepared by treatment with cell wall-digesting enzymes followed by lysis of the consequent protoplasts. Interestingly, the live-cell-immunized mice showed strong cell-mediated immune responses to the membrane fraction (C. albicans membrane antigen [CMA]). In addition, immunization with CMA induced resistance to systemic candidiasis, which disappeared upon administration of anti-CD4 monoclonal antibody. Infusion of splenocytes from the CMA-immunized mice conferred resistance on SCID mice, whereas infusion of CD4(+)-T-cell-depleted splenocytes was unable to induce resistance, indicating the importance of CD4(+) lymphocytes for resistance. These results suggest a potential for the membrane fraction to act as an antigen conferring resistance to systemic candidiasis in place of live cells and also as a source for the isolation of a new antigen.

Adoptive Transfer↗

Immunization with the Candida albicans membrane fraction and in combination with fluconazole protects against systemic fungal infections.

We studied the immunogenicity of a membrane fraction prepared from Candida albicans cells called C. albicans membrane antigen (CMA). The present study revealed that CMA immunization has antifungal activity in mouse models of systemic fungal infection. Immunization of mice by subcutaneous injections of CMA with incomplete Freund adjuvant induced resistance to infections caused not only by C. albicans but also by Aspergillus fumigatus. The level of resistance to candidiasis was as high as that induced by whole-cell immunization. The acquired resistance to candidiasis in the mice immunized with CMA was not diminished by immunosuppressive treatment with cyclophosphamide. The level of resistance to fungal infections was superior to that given by fluconazole (FLC) treatment alone and highly enhanced by the combination with FLC. When CD4(+) cells in CMA-immunized mice were depleted by a monoclonal antibody, the antifungal activity induced by the combination of CMA and FLC was significantly reduced. These results indicate that immunization with CMA is useful for preventing systemic fungal infections and in combination with FLC for increasing resistance after infection.

Animals↗

Incidence and risk factors for subtypes of cerebral infarction in a general population: the Hisayama study.

BACKGROUND AND PURPOSE: We estimated the incidence of first-ever cerebral infarction in regard to its subtypes and analyzed their risk factors separately in a community-based prospective cohort study in Japan. METHODS: Stroke-free subjects (n=1621) aged >/=40 years were followed up for 32 years from 1961. During this period, 298 cerebral infarctions occurred and were divided into 167 lacunar, 62 atherothrombotic, 56 cardioembolic, and 13 undetermined subtypes of infarction on the basis of clinical information including brain imaging and autopsy findings. RESULTS: The age-adjusted incidence of lacunar infarction (3.8 per 1000 person-years for men and 2.0 for women) was higher than that of atherothrombotic infarction (1.2, 0. 7) and cardioembolic infarction (1.3, 0.5) in both sexes. Time-dependent Cox's proportional hazard analysis revealed systolic blood pressure as well as age to be independent risk factors for all subtypes of cerebral infarction except for cardioembolic infarction in men. Additionally, ST depression on ECG, glucose intolerance, and smoking in men and left ventricular hypertrophy on ECG and body mass index in women remained significant risk factors for lacunar infarction. ST depression was also significantly related to events of atherothrombotic infarction in women. The risk of atrial fibrillation for cardioembolic infarction was outstandingly high in both sexes, and left ventricular hypertrophy and lower total cholesterol were additional risk factors for cardioembolic infarction in women. CONCLUSIONS: In this Japanese population, lacunar infarction was the most common subtype of cerebral infarction and had a greater variety of risk factors, including not only hypertension but also ECG abnormalities, diabetes, obesity, and smoking, than did atherothrombotic infarction or cardioembolic infarction.

Adult↗

No toxicity caused by organ accumulation of CPT-11 on multiple injections under clinical regimens in rats.

We investigated the accumulation of CPT-11 and its metabolite (SN-38) in various organs and toxicities on multiple injections of CPT-11 under clinical regimens in SD rats. CPT-11 (16.7 mg/kg equivalent to 100 mg/m2) was administered intravenously by a single injection, or by multiple injections in 1 course (once a week for three consecutive weeks) or 3 courses (1 course repeated 3 times at intervals of 2 weeks). There was no tendency for CPT-11 and SN-38 to accumulate in any organs regardless of the number of injections. Treatment-related changes were not observed in the general condition, body weight, hematology, biochemistry, and organ weights. Histopathological changes induced by CPT-11 were not persistent and the rats made a rapid recovery after the administrations. From these results, it is suggested that there is no toxicity caused by accumulation of CPT-11 and its active metabolite, SN-38, in organs under clinical regimens in rats.

Animals↗

Clinical and pathologic characteristics of lumbar disk herniation in the elderly.

The clinical and pathologic characteristics of lumbar disk herniation in 23 elderly patients (15 men and 8 women) who required surgical treatment were investigated. Average age at surgery was 67.3 years, and average follow-up was 23 months. Preoperatively, the predominant symptom was severe unilateral leg pain, and 13 patients were nonambulatory because of leg pain. Operative treatment included wide laminectomy in 8, hemilaminectomy in 3, fenestration in 10, and osteoplastic laminectomy in 2 patients. Four (17%) patients had disk herniation at the L2-L3 or L3-L4 level. Sequestered herniation with or without migration was observed in 15 (65%) patients. Of 14 sequestered disk fragments examined histologically, 8 (57%) specimens contained cartilaginous or bony end plate with anulus fibrosus or nucleus pulposus. Postoperatively, results were rated as excellent in 11 patients and good in 12; no patient was rated as fair or poor. Severe leg pain affecting activities of daily life is a predominant symptom of disk herniation in the elderly. For patients in whom conservative treatment has failed, operative treatment should be considered. In lumbar disk herniation in the elderly, the incidence of cephalad and lateral herniation is higher than in younger patients. In addition, sequestered and migrated herniations including end plate are frequent.

Activities of Daily Living↗

[Flexibility in the adaptation of the vestibulo-ocular reflex to modified visual inputs in humans].

The vestibulo-ocular reflex (VOR) serves to stabilize images on the retina. To maintain appropriate performance and minimize image slippage throughout life, the VOR is subject to long-term adaptive regulation in response to visual input. Adaptive changes in VOR gain (eye velocity/head velocity) can be evoked either by fitting subjects with magnifying, miniaturizing, or reversing spectacles during normal behavior or by moving a large visual field in or out of phase relative to the subject's head movement. These changes exhibit frequency-selectivity. Here, we examine the flexibility of VOR gains by causing VOR in similar directions to undergo different behavioral gain changes. Nine healthy adults, ranging in age from 24 to 38 (mean 28.5) with no history of neurotological symptoms participated in the study. All subjects demonstrated clinically normal functioning on a screening battery of tests that included combined neurologic and otologic physical examinations. Horizontal and vertical eye positions were recorded by bitemporal DC coupled electrooculography (EOG). The subject sat in a rotating chair. The axis of rotation of the body was always earth-vertical, the interaural axis crossing the axis of rotation of the chair. The head was positioned at 20 degrees down in all experiments and was stabilized in this position using a chin rest. The chair was 78 cm in diameter and was shielded by a half-cylindrical optokinetic screen positioned in front of the subjects. Random dot patterns were projected onto this screen. During per- and post-adaptation periods, goggles were fitted to ensure that the subject was in complete darkness and the chair was rotated sinusoidally. The amplitude of the rotating chair was 30 degrees and 60 degrees. Frequencies of rotation were 0.1 Hz, 0.2 Hz, 0.3 Hz and 0.4 Hz for amplitudes of 30 degrees and 0.1 Hz, 0.2 Hz, and 0.3 Hz for amplitudes of 60 degrees. To induce VOR adaptation, the retinal slippage velocity caused by the visual input of a large field was changed for short-term; the change was produced by a combination of sinusoidal head rotation and random dot patterns. During each adaptation session, the frequencies of sinusoidal head rotation were either 0.1 Hz or 0.3 Hz and the amplitude was 30 degrees. The random dot patterns were synchronized with the sinusoidal head rotation in the same direction to make the retinal slippage zero (x0 experiment) and in the opposite direction to double the retinal slippage (x2 experiment). Therefore, a total of four adaptation protocols were tested. The subjects were asked to fix their eyes on a single dot by looking straight ahead in the x0 experiment and to follow the dot in the random dot pattern in the x2 experiment. Each adaptation session lasted for 30 minutes. Each subject participated in couple of adaptation experiments everyday. The average VOR gain and phase lag were calculated using a Fourier transformation. Out of all the subjects who participated in the x2 adaptation experiment at 0.3 Hz with an amplitude of 30 degrees, seven subjects showed a steady increase in VOR gain during a couple of the trials. One out of the remaining two subjects showed a decrease in VOR gain in all three trials. Another subject showed an increase in VOR gain during three trials and a decrease in two trials. In the x2 adaptation experiment with a range of 30 degrees at 0.3 Hz (peak velocity: 28 degrees/s), the percent change in gain (post-pre/pre) was 133% at the same stimulation and 100% at 0.4 Hz (peak velocity: 37 degrees/s). The percent change in gain was 65% for amplitudes of 60 degrees at 0.1 Hz (peak velocity: 18 degrees/s) and 64% for amplitudes 60 degrees at 0.2 Hz (peak velocity: 37 degrees/s). In the x1 adaptation experiment (30 degrees at 0.3 Hz), the percent change in gain was -62% for the same conditions and -50% for amplitude of 60 degrees at 0.1 Hz and -30% for amplitudes of 60 degrees at 0.2 Hz. No change, in VOR gain was observed at the other frequencies. The

Adaptation, Physiological↗

[Effects of calcium on HPV16 gene transcription in cultured laryngeal epithelial cells].

Human papillomavirus (HPV) gene transcription is closely linked to the differentiation status of infected epithelial cells. A variety of physiological agents, including calcium, regulates the differentiation of cultured epithelial cells. The expression of cytokeratin No.13 (CK13) can be used as a marker for differentiation in cultured laryngeal epithelial cells (HLEC cells). The purpose of this study is to examine the effects of calcium on CK13 expression and HPV16 gene transcription in HLEC cells. We analyzed two types of HPV16-containing HLEC cells: HPV 16-immortalized HLEC cells (HLEC16 cells) and HPV16-positive (infected) cultured laryngeal papilloma cells (HLP16 cells). In the HLEC16 cells, the viral genes were integrated into the host cell chromosomes, while the HLP16 cells contained extra-chromosomal viral genes. The effects of increasing calcium concentrations on CK13 expression were then evaluated using immunocytochemistry. Both the HLP16 and the HLEC16 cells responded to an increased calcium concentration by inducing CK13 expression. In HLP16 and HLEC16 cells, the CK13 expression was undetectable at low calcium concentrations (0.1 mM) but became clearly detectable at high calcium concentrations (1.0 mM). The level of viral RNA was elevated in HLP16 cells with added calcium (1.0 mM) but was similar in HLEC16 cells grown in either low (0.1 mM) or high (1.0 mM) calcium concentrations. These results suggest that a calcium-induced differentiation results in the up-regulation of HPV16 gene transcription in HLP16 cells. The integration of viral gene into the host cell chromosomes may be an important determinant for the differentiation-independent transcription of HPV16 genes.

Calcium↗

Enhancement of hydrolytic activity of sphingolipid ceramide N-deacylase in the aqueous-organic biphasic system.

Lysoglycosphingolipids were produced from glycosphingolipids by using sphingolipid ceramide N-deacylase, which cleaves the N-acyl linkage between fatty acids and sphingosine bases in various glycosphingolipids. The enzyme reaction was done in a biphasic media prepared with water;-immiscible organic solvent and aqueous buffer solution containing the enzyme. We investigated the effects of organic solvents and detergents on lysoglycosphingolipid production in the biphasic system. Among the organic solvents tested, n-butylbenzene, cumene, cyclodecane, cyclohexane, n-decane, diisopropylether, n-heptadecane, and methylcyclohexane promoted hydrolysis of GM1, whereas benzene, chloroform, ethyl acetate, and toluene inhibited GM1 hydrolysis. Hydrolysis of asialo GM1, GD1a, GalCer, and sulfatide was also enhanced by the addition of n-decane. The hydrolytic activity of the enzyme was enhanced by the addition of 0.8% sodium taurodeoxycholate or sodium cholate to the aqueous phase. The most effective hydrolysis of various glycosphingolipids by the enzyme was thus obtained in the aqueous-n-decane biphasic system containing 0.8% sodium taurodeoxycholate. Under this condition, the fatty acids released from GM1 by the action of the enzyme were trapped and diffused into the organic phase, while lysoGM1 remained in the aqueous phase. Thus the almost complete hydrolysis of GM1 was achieved using the biphasic system, while at most 70% of hydrolysis was obtained using normal aqueous media possibly due to the inhibition of hydrolysis reaction by accumulation of fatty acids in the reaction mixture.

Amidohydrolases↗

Hepatocellular carcinoma with extension into the right atrium: report of a successful liver resection by hepatic vascular exclusion using cardiopulmonary bypass.

We report a successful liver resection using cardiopulmonary bypass with, total hepatic vascular exclusion (THVE) for hepatocellular carcinoma (HCC), with extension into the right atrium. A 61-year-old man with a cirrhotic liver was referred to our department with HCC in the medial segment of the left lobe of the liver, and tumor thrombus extending into the right atrium. During surgery, a left lobe and caudate lobe of the liver were transected leaving the left lobe of the liver connected to the inferior vena cava (IVC) by only the left and middle hepatic trunks, and then the intracaval tumor thrombus and the left lobe of the liver were removed en bloc using cardiopulmonary bypass with total hepatic vascular exclusion (THVE). Cardiac arrest was not performed during THVE, and the patient had an uneventful postoperative course and was discharged from the hospital 2 months following surgery. He died of multiple pulmonary metastases 4 years and 8 months after surgery; however, imaging showed no evidence of recurrence in the remnant liver during that period. In conclusion, by performing dissection of the hepatic parenchyma to the hepatic vein prior to removal of the tumor thrombus, the period of extracorporeal circulation, duration of warm ischemic time to the liver, and intraoperative blood loss were all reduced and a radical operation could be performed safely without scattering tumor cells during extirpation of the tumor.

Carcinoma, Hepatocellular↗

Structural requirements of muramylpeptides for induction of Toll-like receptor 2-mediated NF-kappaB activation in CHO cells.

We previously demonstrated that Gram-positive bacteria activated immune cells via CD14 and Toll-like receptor 2 (TLR2). Although peptidoglycan, a major constituent of the bacterial cell wall, substituted for whole organisms, the essential structure of muramylpeptides required to stimulate the cells is not clear. We further investigated the critical determinant for recognition by CD14 and TLR2. Chinese hamster ovary (CHO) fibroblasts, which do not express a functional TLR2 transcript, were transfected with TLR2 or TLR4. These cells were exposed to freeze-dried Staphylococcus epidermidis and were subsequently subjected to the pro-inflammatory transcription factor nuclear factor-kappaB (NF-kappaB)-dependent CD25 expression assay. Heterologous expression of human TLR2, but not TLR4, in CHO cells conferred immune responsiveness to freeze-dried S. epidermidis. A preparation of peptidoglycan from S. epidermidis substituted for whole organisms. Staphylococcus aureus lytic enzyme-digested product (SEPS) from peptidoglycan retained the activity, but hydrolysis of the glycan backbone in SEPS by M-1 endo-N-acetylmuramidase resulted in loss of the activity. These findings showed that cellular activation by Gram-positive cell wall components was mediated by TLR2, but not TLR4, and indicated that the glycan backbone of peptidoglycan is critical for TLR2-mediated NF-kappaB activation.

Acetylmuramyl-Alanyl-Isoglutamine↗