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Biomedical subjects

I Kato

Publications and source records attributed to I Kato.

At least 109 records · Page 6Linked to original sources

External iliac artery occlusion in posterior spinal surgery.

STUDY DESIGN: Report of a case of external iliac artery occlusion occurring as a rare complication of lumbar posterior spinal surgery. OBJECTIVE: To clarify the cause of this rare complication and recommend methods for preventing its recurrence. SUMMARY OF BACKGROUND DATA: Several cases of central retinal artery occlusion after posterior spinal surgery have been reported, but there has been no reported case of external iliac artery occlusion after posterior spinal surgery. METHODS: A 65-year-old woman who had a 32-year history of systemic lupus erythematosus underwent posterior decompression and spinal fusion for degenerative scoliosis. She was supported on a Hall frame during the operation. Three hours after surgery, paralysis and sensory impairment of the left leg and cyanosis of the toes of the left foot were noted. The popliteal, dorsalis pedis, and posterior tibial pulses were not palpable. Angiography showed complete occlusion of the external iliac artery, and emergency removal of the thrombus was performed. RESULTS: One year later, neurologic symptoms were absent, and the leg vessels were normal. CONCLUSIONS: Prolonged direct pressure on the inguinal region during posterior spinal surgery on a Hall frame may cause external iliac artery occlusion. Early recognition and adequate treatment can prevent serious sequelae.

Aged↗

Iron intake, body iron stores and colorectal cancer risk in women: a nested case-control study.

Accumulated evidence suggests that increased body iron stores may increase the risk of colorectal cancer, possibly via catalyzing oxidation reactions. We examined the relationship between iron status and colorectal cancer in a case-control study nested within the New York University Women's Health Study cohort. For 105 incident cases of colorectal cancer with an average follow-up of 4.7 years and 523 individually matched controls, baseline levels of serum iron, ferritin, total iron binding capacity (TIBC) and transferrin saturation were determined as indicators of body iron stores, and total iron intake was assessed based on their diet and supplement intake. Overall, there were no associations between the risk of colorectal cancer and any of these indices except for serum ferritin, which showed a significant inverse association. When analyzed by subsite, there was an increasing trend in risk of cancer of the proximal colon with increasing total iron intake (p-value for trend = 0.04). In addition, a significantly increased risk of colorectal cancer associated with higher total iron intake [odds ratio (OR) = 2.50; 95% confidence interval (CI): 1.06-5.87] was observed among subjects with higher intake of total fat. Our results do not support a role of increased body iron stores in the development of colorectal cancer, but suggest that luminal exposure to excessive iron may possibly increase the risk in combination with a high fat diet.

Adult↗

Comparison of active and cancer registry-based follow-up for breast cancer in a prospective cohort study.

The authors compared the relative effectiveness of two distinct follow-up designs in prospective cohort studies--the active approach, based on direct contact with study subjects, and the passive approach, based on record linkages with population-based cancer registries--utilizing available information from the New York University Women's Health Study (WHS) and the New York State Cancer Registry (NYSCR). The analyses were limited to breast cancer cases identified during the period 1985-1992, for which follow-up was considered reasonably complete by both the WHS and the NYSCR. Among 12,947 cohort members who reported a New York State address, 303 pathologically confirmed cases were identified through active follow-up and 284 through record linkage. Sixty-three percent of cancers were identified by both sources, 21% by the WHS only, and 16% by the NYSCR only. The agreement was appreciably better for invasive cancers. The percentage of cases identified only by the NYSCR was increased among subjects whose active follow-up was incomplete, as well as among nonwhites, obese patients, and parous patients. This suggests that relying on either type of follow-up alone may introduce certain biases in evaluating risk factors for breast cancer. Combining both approaches appears to be a better strategy in prospective cohort studies.

Adult↗

CD38 disruption impairs glucose-induced increases in cyclic ADP-ribose, [Ca2+]i, and insulin secretion.

Increases in [Ca2+]i in pancreatic beta cells, resulting from Ca2+ mobilization from intracellular stores as well as Ca2+ influx from extracellular sources, are important in insulin secretion by glucose. Cyclic ADP-ribose (cADPR), accumulated in beta cells by glucose stimulation, has been postulated to serve as a second messenger for intracellular Ca2+ mobilization for insulin secretion, and CD38 is thought to be involved in the cADPR accumulation (Takasawa, S., Tohgo, A., Noguchi, N., Koguma, T., Nata, K., Sugimoto, T., Yonekura, H., and Okamoto, H. (1993) J. Biol. Chem. 268, 26052-26054). Here we created "knockout" (CD38(-/-)) mice by homologous recombination. CD38(-/-) mice developed normally but showed no increase in their glucose-induced production of cADPR in pancreatic islets. The glucose-induced [Ca2+]i rise and insulin secretion were both severely impaired in CD38(-/-) islets, whereas CD38(-/-) islets responded normally to the extracellular Ca2+ influx stimulants tolbutamide and KCl. CD38(-/-) mice showed impaired glucose tolerance, and the serum insulin level was lower than control, and these impaired phenotypes were rescued by beta cell-specific expression of CD38 cDNA. These results indicate that CD38 plays an essential role in intracellular Ca2+ mobilization by cADPR for insulin secretion.

ADP-ribosyl Cyclase↗

Identification of HLA-A24 epitope peptides of carcinoembryonic antigen which induce tumor-reactive cytotoxic T lymphocyte.

Carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a potential target for specific immunotherapy. HLA-A24 is the most frequent allele among Japanese and is also frequently present in Asians and Caucasians. We tested CEA-encoded HLA-A24 binding peptides for their capacity to elicit anti-tumor cytotoxic T lymphocytes (CTL) in vitro. For this purpose, we used CD8+ T lymphocytes from peripheral blood mononuclear cells (PBMC) of a healthy donor and autologous peptide-pulsed dendritic cells as antigen-presenting cells. This approach enabled us to identify 2 peptides, QYSWFVNGTF and TYACFVSNL, which were capable of eliciting CTL lines that lysed tumor cells expressing HLA-A24 and CEA. The cytotoxicity to tumor cells by the CTL lines was antigen-specific since it was inhibited by peptide-pulsed cold target cells as well as by anti-class I major histocompatibility complex (MHC) and anti-CD3 monoclonal antibodies (MAbs). The antigen specificity of the 2 CTL lines was examined using several tumor cell lines of various origins and for their peptide-dose responses. The identification of these novel CEA epitopes for CTL offers the opportunity to design and develop epitope-based immunotherapeutic approaches for treating HLA-A24+ patients with tumors that express CEA.

Amino Acid Sequence↗

An aureobasidin A resistance gene isolated from Aspergillus is a homolog of yeast AUR1, a gene responsible for inositol phosphorylceramide (IPC) synthase activity.

The AUR1 gene of Saccharomyces cerevisiae, mutations in which confer resistance to the antibiotic aureobasidin A, is necessary for inositol phosphorylceramide (IPC) synthase activity. We report the molecular cloning and characterization of the Aspergillus nidulans aurA gene, which is homologous to AUR1. A single point mutation in the aurA gene of A. nidulans confers a high level of resistance to aureobasidin A. The A. nidulans aurA gene was used to identify its homologs in other Aspergillus species, including A. fumigatus, A. niger, and A. oryzae. The deduced amino acid sequence of an aurA homolog from the pathogenic fungus A. fumigatus showed 87% identity to that of A. nidulans. The AurA proteins of A. nidulans and A. fumigatus shared common characteristics in primary structure, including sequence, hydropathy profile, and N-glycosylation sites, with their S. cerevisiae, Schizosaccharomyces pombe, and Candida albicans counterparts. These results suggest that the aureobasidin resistance gene is conserved evolutionarily in various fungi.

Amino Acid Sequence↗

Lactic acid bacterium potently induces the production of interleukin-12 and interferon-gamma by mouse splenocytes.

We previously have reported that the lactic acid bacterium, Lactobacillus casei strain Shirota (LcS), shows marked antitumor activities and an ability to modify immune responses. In this study, we examined whether LcS can induce the production of interleukin (IL)-12 and interferon-gamma (IFN-gamma), which are important cytokines for antitumor and antimicrobial immunity, from murine splenocytes in vitro in order to clarify the mechanisms of its immune modification. Stimulation by LcS induced a marked production of IL-12 by X-ray-irradiated splenocytes (X-irr-Spl). The production of IL-12 by X-irr-Spl was independent of the presence of nylon wool column-passed splenocytes (NW-Spl). IFN-gamma was produced by splenocytes by the stimulation with concanavalin A (Con A). LcS showed a synergistic stimulatory effect on the ConA-induced production of IFN-gamma. In addition, X-irr-Spl were required for the IFN-gamma; production by NW-Spl treated with LcS. The IFN-gamma production was reduced by anti-IL-12 antibody treatment. NW-Spl produced IFN-gamma following treatment with recombinant IL-12. Thus, we confirmed that IFN-gamma production by splenocytes was the result of the production of IL-12 from X-irr-Spl stimulated by LcS. Furthermore, in BALB/c mice, the oral administration of viable LcS augmented the production of IFN-gamma but not that of IL-4 or IL-5 by splenocytes. Thus, we suggested that LcS primarily activated X-irr-Spl, probably macrophages, and these cells secreted IL-12. The IL-12 induced by LcS stimulated the production of IFN-gamma.

Animals↗

Chemo-enzymatic synthesis of a calcitonin derivative containing a high-mannose type oligosaccharide by endo-beta-N-acetylglucosaminidase from Arthrobacter protophormiae.

Chemo-enzymatic addition of a high-mannose type oligosaccharide to eel calcitonin (CT), a calcium-regulating hormone, was examined. The endo-beta-N-acetylglucosaminidase from Arthrobacter protophormiae (Endo-A) transglycosylated the Man(6)-GlcNAc moiety from an ovalbumin-derived high-mannose type glycosyl asparagine, Asn(Man(6)-GlcNAc(2))-OH, to a calcitonin derivative, [Asn(GlcNAc)(3)]-CT, in which the N-acetyl-d-glucosamine (GlcNAc) is attached to the third l-asparagine (Asn) residue of the peptide, and a calcitonin derivative containing a high-mannose type oligosaccharide, [Asn(Man(6)-GlcNAc(2))(3)]-CT, was synthesized. The optimal reaction conditions for the synthesis of [Asn(Man(6)-GlcNAc(2))(3)]-CT from Asn(Man(6)-GlcNAc(2))-OH and [Asn(GlcNAc)(3)]-CT catalyzed by Endo-A were examined. The transglycosylation yield relative to the concentration of the [Asn(GlcNAc)(3)]-CT added was 32.7%, and 4.42 mg of [Asn(Man(6)-GlcNAc(2))(3)]-CT was prepared.

Journal Article↗

Epidemiologic correlates with menstrual cycle length in middle aged women.

While irregular menstruations have been associated with lower cumulative exposure to the ovarian steroids, shorter regular cycles have been postulated to increase the cumulative exposure. Epidemiological correlates with menstrual patterns were analyzed among 4900 premenopausal women aged 45 or younger from the New York University Women's Health Study. The length of regular menstrual cycles increased with increasing age at menarche, body mass index and parity, but decreased with age, nonwhite racial background and current smoking. The likelihood of irregular cycles increased with increasing age, body mass index and number of cigarettes smoked per day. With adjustment for age, body mass index and number of cigarettes smoked per day, the risk of irregular cycles was marginally positively associated with total fat intake.

Adult↗

Epidemiologic correlates of serum folate and homocysteine levels among users and non-users of vitamin supplement.

Lower serum folate and higher serum homocysteine levels are known risk factors for various conditions. Thus, epidemiologic correlates with these measurements were studied for 256 multivitamin users and 230 non-users who were middle-aged women. Both serum folate and homocysteine levels increased with advancing age in both multivitamin users (P < 0.01 and P < 0.01) and non-users (P = 0.08 and P < 0.01). Among non-users, higher intake of vegetables, fruits, cold cereals and total protein were associated positively with serum folate and inversely with homocysteine levels. There were 25-74% increases in serum folate and 10-15% decreases in serum homocysteine between 1st and 4th quartiles of intake of these food/nutrients. In addition, 26% lower serum folate and 18% higher serum homocysteine were observed for those smoking 20 or more cigarettes per day compared with non-smokers. Among multivitamin users, body weight was correlated inversely with serum folate (P < 0.01) and positively with serum homocysteine levels (P = 0.04), while no correlates were found among lifestyle factors. Regular use of multivitamins increased serum folate about fourfold and decreased homocysteine twofold. These results suggest that multivitamin use can offset the effects of an unhealthy lifestyle on these serum markers, and that levels of serum folate and homocysteine can also be favorably influenced by healthier diet and abstinence from smoking.

Adult↗

Serum folate, homocysteine and colorectal cancer risk in women: a nested case-control study.

Accumulating evidence suggests that folate, which is plentiful in vegetables and fruits, may be protective against colorectal cancer. The authors have studied the relationship of baseline levels of serum folate and homocysteine to the subsequent risk of colorectal cancer in a nested case-control study including 105 cases and 523 matched controls from the New York University Women's Health Study cohort. In univariate analyses, the cases had lower serum folate and higher serum homocysteine levels than controls. The difference was more significant for folate (P < 0.001) than for homocysteine (P = 0.04). After adjusting for potential confounders, the risk of colorectal cancer in the subjects in the highest quartile of serum folate was half that of those in the lowest quartile (odds ratio, OR = 0.52, 95% confidence interval, CI = 0.27-0.97, P-value for trend = 0.04). The OR for the highest quartile of homocysteine, relative to the lowest quartile, was 1.72 (95% CI = 0.83-3.65, P-value for trend = 0.09). In addition, the risk of colorectal cancer was almost twice as high in subjects with below-median serum folate and above-median total alcohol intake compared with those with above-median serum folate and below-median alcohol consumption (OR = 1.99, 95% CI = 0.92-4.29). The potentially protective effects of folate need to be confirmed in clinical trials.

Aged↗

Autocrine and paracrine motility factors and their involvement in invasiveness in a human oral carcinoma cell line.

Invasive potentials of malignant cancer cells are regulated by cell motility factors. To examine the regulation of motility and invasiveness in oral squamous carcinoma, we investigated autocrine- and/or paracrine-acting cell motility factors, using a newly established human cell line (IF cells) from oral squamous cell carcinoma, which has highly invasive and metastatic characteristics. Conditioned medium derived from IF cells stimulated cell scattering and migration of GB-d1 gallbladder carcinoma cells, indicating that IF cells secreted cell motility factors. Using antibodies, IF-derived cell motility factors proved to be transforming growth factor (TGF)-alpha and TGF-beta1. Antibodies against TGF-alpha and TGF-beta1 inhibited autonomous migration of the IF cells. On the other hand, in vitro invasion of IF cells was strongly enhanced by hepatocyte growth factor (HGF) but only slightly by TGF-alpha and TGF-beta1. The conditioned medium from fibroblasts enhanced in vitro invasion of IF cells, an event abrogated by anti-HGF antibody, but not by antibodies against TGF-alpha and TGF-beta1. Importantly, IF cells secreted a factor inducing HGF production in fibroblasts and the factor was identified as interleukin-1, which means that a mutual interaction exists between tumour cells and fibroblasts, as mediated by the HGF/HGF-inducer loop. These results indicate that IF cells utilize TGF-alpha and TGF-beta1 as autocrine-acting motility factors and HGF as a paracrine-acting motility factor, and that invasiveness of IF cells is particularly stimulated by HGF derived from stromal fibroblasts. Utilization of multiple cell motility/invasion factors that act in distinct pathways may confer highly invasive and metastatic potentials in IF oral squamous carcinoma cells.

Carcinoma, Squamous Cell↗

Two-dimensional electrophoresis of Malassezia allergens for atopic dermatitis and isolation of Mal f 4 homologs with mitochondrial malate dehydrogenase.

The yeast Malassezia furfur is a natural inhabitant of the human skin microflora that induces an allergic reaction in atopic dermatitis. To identify allergens of M. furfur, we separated a crude preparation of M. furfur antigens as discrete spots by 2-D PAGE and detected IgE-binding proteins using sera of atopic dermatitis patients. We identified the known allergens, Mal f 2 and Mal f 3, and determined N-terminal amino acid sequences of six new IgE-binding proteins including Mal f 4. The cDNA and genomic DNA encoding Mal f 4 were cloned and sequenced. The gene was mitochondrial malate dehydrogenase and encoded Mal f 4 composed of 315 amino acids and a signal sequence of 27 amino acids. We purified Mal f 4, which had a molecular mass of 35 kDa from a membrane fraction of a lysate of cultured cells. Thirty of 36 M. furfur-allergic atopic dermatitis patients (83.3%) had elevated serum levels of IgE to purified Mal f 4, indicating that Mal f 4 is a major allergen. There was a significant correlation of the Phadebas RAST unit values of Mal f 4 and the crude antigen, but not between Mal f 4 and the known allergen Mal f 2.

Allergens↗

Dopamine penetrates to the central nervous system in developing rats.

BACKGROUND: The purpose of this study was to evaluate whether or not dopamine (DA) can penetrate to the central nervous system (CNS) from the blood in the infantile period in rats. METHODS: In a preliminary experiment, we administered a 50 mg/kg dose of DA hydrochloride, intraperitoneally, to 7-day-old rats (DA 50 mg/kg group), obtaining cerebrospinal fluid (CSF) both before and at 5, 10, 20, 30, 60 and 120 min after administration. The CSF levels of DA and its main metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were then measured. Next, we investigated the DA transfer from blood to the CNS by administering doses of 1, 5, 10 and 30 mg/kg DA hydrochloride (DA 1, 5, 10 and 30 mg/kg groups). In these groups, CSF samples were obtained only at 10 and/or 60 min after DA administration, based on the results of the DA 50 mg/kg group. RESULTS: The DA concentrations in CSF significantly increased compared with values before DA administration in the DA 50 mg/kg group. The DA concentrations in the DA 30 mg/kg group, DOPAC concentrations in the DA 5, 10 and 30 mg/kg groups, and HVA concentrations in all groups were significantly higher than in the control (saline injection) group. CONCLUSIONS: These findings suggest easy DA transfer from blood to the CNS and immaturity of the blood-brain barrier for DA in the infantile period in rats.

Animals↗

Effect of hyperinsulinemia on renal function in a general Japanese population: the Hisayama study.

BACKGROUND: Insulin resistance and hyperinsulinemia induce glomerular hypertension and hyperfiltration, which may result in glomerulosclerosis. However, the relationship between hyperinsulinemia and renal function is uncertain. METHODS: To elucidate whether hyperinsulinemia plays a significant part in the initiation and development of renal dysfunction, we examined in 1988 the relationship between serum insulin and renal function on data from a cross-sectional community survey conducted among residents from Hisayama Town, Japan, who were aged 40 to 79 years old. A total of 1065 men (72.0% of the total population in the same age range) and 1381 women (79.0%) without renal failure (creatinine clearance of more than 30 ml/min) underwent a comprehensive examination, including a 75 g oral glucose tolerance test. RESULTS: The correlation analysis showed that serum insulin, blood pressure, total cholesterol, low-density lipoprotein cholesterol, triglycerides, and body mass index were all negatively correlated with the reciprocal of serum creatinine level (P < 0.01), and alcohol intake was positively correlated (P < 0.05) in both sexes. High-density lipoprotein cholesterol and smoking habits were positively correlated (P < 0.05) in men. When the subjects were divided into quartiles based on the sum of fasting and two-hour postloading insulin levels, the averages of the reciprocal of serum creatinine were significantly lower in the fourth quartile (0.90 +/- 0.10 for men and 1.10 +/- 0.14 for women) compared with the lowest quartile (0.95 +/- 0.12 and 1.13 +/- 0.13, respectively) in both sexes (P < 0.05). In multiple regression analysis, the correlation between the sum of insulin levels and the reciprocal of serum creatinine remained significant even after controlling for age, sex, body mass index, blood pressure, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, alcohol intake, and smoking habits. We could not find appropriate correlations of creatinine clearance calculated by the Cockcroft-Gault formula with the covariates including serum insulin. CONCLUSIONS: The findings of this study suggest that hyperinsulinemia is a significant relevant factor of renal function in the general population.

Adult↗

Body fat distribution and obesity in pre- and postmenopausal breast cancer.

BACKGROUND: Excessive body weight is known to increase the risk of postmenopausal, but not premenopausal breast cancer. Some studies have suggested that being overweight is protective against premenopausal breast cancer, but the evidence is not compelling. Much less is known about the role of body fat distribution in either pre- or postmenopausal breast cancer. METHODS: Breast cancer risk was examined in relation to body weight, height, Quetelet index (kg/m2), and waist/hip ratio (WHR) in the New York University Women's Health Study, a prospective cohort study. Cases were 109 premenopausal and 150 postmenopausal women diagnosed with breast cancer between 1985 and 1994. Non-cases were 8,157 cohort members free of breast cancer. RESULTS: Among premenopausal women, there was an increasing risk of breast cancer with increasing WHR. The relative risk (RR) of breast cancer increased to 1.72 (95% confidence interval [CI]: 1.0-3.1) in the upper quartile of WHR. The association was limited to subjects who had elevated Quetelet index, but not among those with lower weight. Overall, Quetelet index itself was not related to breast cancer risk in the premenopausal group, but there was a protective association among those ranking below the median WHR. In postmenopausal women, the RR for breast cancer increased to 2.36 (95% CI: 1.4-3.9) in the upper quartile of Quetelet index, but there was no association with WHR. Height was not associated with breast cancer in this study. CONCLUSIONS: The study confirms that excessive body weight increases breast cancer risk in postmenopausal women. On the contrary, in premenopausal women, excessive body weight may be protective among women who have a lower-body type of fat accumulation (low WHR). An upper-body fat accumulation (high WHR) is a predictor of breast cancer risk in premenopausal women, and this effect is especially pronounced among subjects who are overweight.

Adipose Tissue↗

Lambda5 is required for rearrangement of the Ig kappa light chain gene in pro-B cell lines.

Lambda5 associates with V(pre-B) to form the surrogate light (L) chain. The phenotype of lambda5 knockout mice showed severe impairment of B cell development from pro-B to immature B cell stages. To investigate the function of the surrogate L chain at this stage, we restored expression of lambda5 to lambda5-deficient pro-B cell lines which were established from bone marrow cells of lambda5 knockout mice in the presence of IL-7 and a stromal cell line. Some of these lines are severely impaired in B cell development from pro-B to immature B cell stages as is seen in vivo in lambda5 knockout mice. Restoration of lambda5 protein by retroviral-mediated gene transfer into established lambda5-deficient pro-B cell lines induced rearrangement of the Ig kappa L chain genes after removal of IL-7 from the culture. Immunoprecipitation revealed that the restored lambda5 in the cell line is coupled with V(pre-B) to form the surrogate L chain. The results demonstrate that formation of a complete surrogate L chain, consisting of both lambda5 and V(pre-B), stimulates efficient rearrangement of the kappa L chain genes.

Animals↗

Induction of anti-thymocyte/T lymphocyte antibodies in mice injected with lipopolysaccharides from periodontopathic bacteria.

We examined the levels of anti-thymocyte/T lymphocyte autoantibody (ATA) in the serum of mice injected intraperitoneally with lipopolysaccharides (LPS) from periodontopathic bacteria; Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Capnocytophaga ochracea, and non-oral Escherichia coli. All of the LPS induced IgM-ATA. Among these, LPS from C. ochracea induced the highest level of IgM-ATA, whereas that of P. gingivalis induced the lowest. The peritoneal T lymphocytes of mice injected with LPS were bound by IgM-ATA. Peritoneal B-1 (CD5+B) cells stimulated by each LPS produced much more IgM-ATA than splenic B-2 (CD5-B) cells, suggesting that B-1 cells might be responsible for the production of these antibodies. Serum of mice injected with C. ochracea and F. nucleatum LPS showed cytotoxicity against thymocytes in the presence of rabbit complements. Binding and cytotoxicity were confirmed by IgM purified from serum of the mice injected with C. ochracea LPS. Furthermore, serum of mice treated with C. ochracea, F. nucleatum or A. actinomycetemcomitans LPS inhibited the proliferation of thymocytes. However, purified IgM from the serum of mice treated with C. ochracea LPS failed to produce the same inhibition. Our results suggest that LPS from certain species of periodontopathic bacteria can induce IgM-ATA in the serum and these antibodies may modulate the local immune network in periodontal tissues.

Aggregatibacter actinomycetemcomitans↗