Search PubMed⌕ Search

Biomedical subjects

Y Nitta

Publications and source records attributed to Y Nitta.

At least 91 records · Page 5Linked to original sources
PubMed1994

Remodelling of microvessels by coronary hypertension or cardiac hypertrophy in rats.

We attempted to clarify the individual effects of coronary hypertension and ventricular pressure-overload on the remodelling of coronary arterial microvessels. We examined structural vascular changes in the right ventricular free walls using two experimental rat models: 12-week ascending aortic banding, i.e. a model of coronary hypertension without ventricular pressure-overload and 12-week pulmonary artery banding, i.e. a model of ventricular pressure-overload without coronary hypertension. In vivo peak systolic left ventricular pressure and left ventricular weight to body weight ratio in the aortic banding model increased to 198 +/- 10 mmHg and by 39% above the controls, respectively. In vivo peak right ventricular pressure and right ventricular weight to body weight ratio in the pulmonary artery banding model increased to 87 +/- 7 mmHg and by 69% above the controls, respectively. The right coronary reserve measured by the Doppler method decreased in both experimental models. Aortic banding increased the medial area and perivascular collagen to lumen area ratios in the microvessels > 30 microns in lumen diameter but not in those < 30 microns. Pulmonary artery banding increased the perivascular collagen to lumen area ratio in the microvessels < 60 microns, but not in those > 60 microns. Medial thickening was not observed over the whole range of lumen diameter. These results suggest that the mechanisms responsible for the remodelling of coronary microvessels differ between non-hypertrophied hearts with coronary hypertension and hypertrophied hearts without coronary hypertension.

Animals↗
PubMed1994

Identification of programmed cell death in normal human skin tissues by using specific labelling of fragmented DNA.

Programmed cell death (PCD) in normal human skin tissues was studied by using in situ specific labelling of fragmented DNA. This labelling method clearly stained the nuclei of Henle's layer in the bulb of the anagen hair follicle in serial sections, and the nuclei of the inner root sheath cuticle cells and Huxley's layer cells showed positive staining in the upper part of the hair follicles. This staining pattern was consistent with the sequence of keratinization in the three layers. The nuclei of differentiated cells located at the centre of the sebaceous glands, and those of the granular keratinocyte layer, were also stained. These findings suggest that PCD might play a key role in the terminal differentiation of the epidermis and epidermal appendages.

Apoptosis↗
PubMed1994

Significance of tubuloreticular structures forming in Daudi cells cultured with sera from mothers bearing infants with neonatal lupus erythematosus.

It is known that infants with neonatal lupus erythematosus (NLE) may be born to mothers whose sera are positive for the anti-Ro/SSA antibody. However, women who have this antibody do not always give birth to children with NLE. We have demonstrated tubuloreticular structures in vascular endothelial cells in the skin lesions of infants with NLE. Tubuloreticular structures could no longer be detected at the site of the lesions once the annular erythema had resolved, and the anti-Ro/SSA antibody test had become negative. The probability of a child being born with NLE was assessed by observing whether tubuloreticular structures were formed in Daudi cells cultured with sera from eight mothers who were anti-Ro/SSA antibody positive. Tubuloreticular structures formed in Daudi cells cultured with sera from four mothers who bore infants with NLE, but not in Daudi cells cultured with sera from four other mothers who bore normal infants. These results suggest that women who are positive for the anti-Ro/SSA antibody have a higher risk of bearing infants with NLE if tubuloreticular structures are formed in Daudi cells cultured with sera from these women, whereas this risk is lower if tubuloreticular structures do not develop in Daudi cells.

Adult↗
PubMed1994

[Basic and clinical studies of fleroxacin on infectious enteritis. Research Group of AM-833 on infectious enteritis].

A clinical study was conducted on fleroxacin (FLRX) in 143 patients and carriers with infectious enteritis (shigellosis, Salmonella enteritis, Campylobacter enteritis, pathogenic Escherichia coli enteritis, Vibrio parahaemolyticus enteritis, cholera, multiple bacterial infections, pathogen-negative enteritis). Furthermore, its antibacterial activity against clinical isolates, fecal concentration and effect on fecal microflora were conducted. FLRX was administered orally in doses of 200 mg once a day (200 mg group) or 300 mg once a day (300 mg group) for 3 days to cholera, for 7 days to Salmonella enteritis and for 5 days to the other infectious enteritis. The clinical efficacy rates were 100% in both the 200 mg and 300 mg groups. The bacteriological efficacy rates were 100% against Shigella spp., Salmonella spp., pathogenic E. coli, V. parahaemolyticus and V. cholerae O1, and 63.6% against Campylobacter spp. in the 200 mg group. The rates of the 300 mg group were 93.3% against Shigella spp., and 100% against Campylobacter spp. and pathogenic E. coli. As adverse effects, skin rash was observed in 1 case each in both groups (1.1%, 2.1%). Abnormal laboratory findings consisted of 1 case of increased eosinophils and 1 case of elevated GOT and GPT levels in the 200 mg group (2.8%), and 1 case of elevated GPT in the 300 mg group (2.9%). The clinical usefulness rates were 92.9% and 93.3% in the 200 mg and 300 mg groups, respectively. Antibacterial activity was somewhat inferior to that fo ciprofloxacin and equal to or better than that of norfloxacin, demonstrating MIC90 values against Shigella spp., Salmonella spp., pathogenic E. coli, V. parahaemolyticus and Campylobacter spp. of 0.1, 0.2, 0.1, 0.2 and 0.78 micrograms/ml, respectively. Peak fecal concentrations of the drug were 49.0 micrograms/g and 274.4 micrograms/g in the 200 mg group, and 43.3 micrograms/g and below the detection limit (5.0 micrograms/g) in the 300 mg group. With respect to fecal microflora (4 cases), a decrease in Enterobacteriaceae was observed in 3 cases during dosing. But this change showed a tendency to recover after completion of dosing. No effects were observed on anaerobic bacteria.

Adolescent↗
PubMed1994

Diminished heat shock protein 70 mRNA induction in aged rat hearts after ischemia.

Vulnerability of aged hearts to ischemia may be due to defects in protective mechanisms provided by heat shock proteins (HSPs). To determine whether there is a defect in the induction of HSPs by ischemia in old hearts, HSP72 and HSP73 (inducible and constitutive HSP70, respectively) mRNA induction was examined in young (2-mo-old; n = 36) and old (18-mo-old; n = 32) rat hearts. Transient (10- or 20-min) ischemia was applied by tightening a snare placed around left coronary arterial branches 3 days before examination to avoid the effect of operation on induction. HSP72 mRNA was induced markedly in young hearts after 10-min ischemia, peaked at 2 h, but was induced only slightly in old hearts. HSP73 mRNA was also induced in young hearts, peaked at 4 h, but was not induced in old hearts. The mRNAs were markedly induced in old hearts as well after 20-min ischemia, which was accompanied by the induction of HSP72 protein. Thus the age-related modulation of HSP72 and HSP73 mRNAs suggests a defective sensing mechanism for ischemia in old hearts.

Aging↗
PubMed1994

Responses to hemodynamic stress in the aged heart.

In aged individuals the incidence of heart failure is higher than in younger subjects. Ischemic events are also common in the aged heart because of changes in the coronary vasculature and myocytes caused by aging. Adaptational responses to increased hemodynamic overload and to ischemia in the aged heart are discussed at the molecular, cellular and organ levels. One characteristic of the aged heart is a limited capacity for adaptation with hypertrophy to increased mechanical load. This age-related attenuation of the hypertrophic response may be attributed to the diminished induction of proto-oncogenes such as c-fos, c-myc and c-jun by hemodynamic stress. This diminution results from the aging of the heart per se and may be modulated by extracardiac factors. An age-related diminution was also observed in the mRNA induction of heat shock proteins by transient ischemia. However, this diminished induction of immediate early genes in the aged heart was not observed after more severe stress. With regard to the coronary vasculature, the age at which pressure-overload begins seems to be one of the important factors which determine the vascularity of hypertrophied hearts. Late-onset pressure-overload decreased dilator reserve in spite of the absence of myocardial hypertrophy. Thus, the responses to stress in the aged heart are quite different from those in the young heart. The limited capacity for adaptation to hemodynamic overload and poor protective mechanisms against stress may be causes of the higher incidence of heart failure in the aged.

Aged↗
PubMed1993

Sweet potato beta-amylase. Primary structure and identification of the active-site glutamyl residue.

The complete amino acid sequence of a subunit of sweet potato beta-amylase, a homotetramer, was established by sequence analysis of peptides obtained by digestions with Achromobacter protease I and Staphylococcus aureus V8 protease and by cyanogen bromide cleavage of the S-carboxymethylated subunit. The subunit of the enzyme is a single polypeptide consisting of 498 amino acid residues. It showed 50-60% identity in the amino acid sequence with those of beta-amylases from soybean and barley, while it about 25% with those of three bacterial beta-amylases deduced from the cDNA sequences. Sweet potato beta-amylase was completely inactivated with 2,3-epoxypropyl alpha-D-[U-14C]glucopyranoside. Sequence analysis of the inactivated enzyme revealed that Glu187 was specifically esterified by the affinity labeling with the above reagent, proposing that Glu187 is a potent candidate involved directly in the catalysis with this plant beta-amylase.

Amino Acid Sequence↗
PubMed1993

Preferential expression of HSC70 heat shock mRNA in gerbil heart after transient brain ischemia.

Inductions of mRNAs for heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 were examined in the cerebral cortex, cerebellum, heart, lung, kidney, and liver of gerbils after a 10-min transient forebrain ischemia. HSP70 mRNA was normally expressed in a small amount in the cerebellum, lung, and kidney, but was not expressed in the heart or liver in a detectable amount. A very small amount of HSP70 mRNA was also present in the cerebral cortex. HSC70 mRNA was normally present in all the organs examined with a variety in the amount. Eight hours after the cerebral ischemia, the level of HSP70 mRNA increased in the cerebral cortex, lung, and kidney. HSC70 mRNA levels also increased in all the organs. However, the increase of HSC70 mRNA was remarkable in the heart. Transient cerebral ischemia caused subsequent hyperthermia. Treatment of gerbils with an artificial hyperthermia without cerebral ischemia increased the HSP70 and HSC70 mRNA levels as well. However, the HSC70 mRNA level in the heart after cerebral ischemia was much higher than that in the case with hyperthermic treatment. These results suggest that HSC70 mRNA was preferentially induced in the heart after transient forebrain ischemia that was not only due to the subsequent hyperthermia.

Animals↗
PubMed1993

Aminoalkylbisphosphonates, potent inhibitors of bone resorption, induce a prolonged stimulation of histamine synthesis and increase macrophages, granulocytes, and osteoclasts in vivo.

Aminoalkyl derivatives of bisphosphonates are potent inhibitors of bone resorption. A single I.P. injection of 4-amino-1-hydroxybutylidene-1,1-bis-phosphonate (AHBuBP) induced a prolonged enhancement of histidine decarboxylase (HDC) activity in the bone marrow, spleen, lung, and liver of mice and resulted in an increase in histamine. The induction of HDC by the agent was dose dependent (16-80 mumol/kg) and peaked 3-4 days after its injection (40 mumol/kg). Repeated S.C. injections of smaller doses of AHBuBP (0.32 or 1.6 mumol/kg/day) for 4 days also enhanced HDC activity. However, the minimum dose capable of inhibiting bone resorption (0.064 mumol/kg/day) was lower than that inducing HDC. Unexpectedly, AHBuBP, at the doses inducing HDC, increased macrophages, granulocytes, and even osteoclasts. The size of osteoclasts was also enlarged by the agent. Another aminobisphosphonate, 3-amino-1-hydroxypropylidene-1,1-bisphosphonate, but none of non-amino derivatives, also exhibited essentially the same effects as those of AHBuBP. These results indicate that in spite of increase in osteoclasts and their enlargement, bone resorption is still inhibited by amino bisphosphonates. As granulocyte and granulocyte-macrophage colony-stimulating factors and interleukin-3 induce HDC in hematopoietic organs, and histamine has a hematopoietic activity, the HDC induction by aminobisphosphonates may be relevant to the proliferation of progenitor cells of macrophages, granulocytes, and osteoclasts.

Alendronate↗
PubMed1993

[Investigation of subjective symptoms among visual display terminal users and their affecting factors--analysis using log-linear models].

In order to evaluate factors affecting visual and musculoskeletal symptoms by visual display terminal (VDT) operation, a questionnaire survey was conducted among clerical workers in Chiba university. The results were as follows: 1) Of these workers, 81.9% engaged in VDT operation. For most of the subjective symptoms, the prevalence rates tended to increase with the degree of VDT use. 2) These complaints were combined to give visual and musculoskeletal symptom scores. Both of the scores were higher among females than males, and the musculoskeletal symptom score was significantly higher. No difference was found in regard to age. 3) Analysis using log-linear models was performed to evaluate the effects of sex and age. The results showed that the visual and musculoskeletal symptom scores were significantly higher among the workers operating VDTs for one or more hours per day than among those who did not operate them at all. Analysis of the effects of VDT workloads revealed that VDT use for five or more days per week significantly increased the prevalence rates of both symptoms. Their use for less than four days per week affected neither of the symptoms. With regard to operating time per day or length of VDT use, no differences were found. 4) This investigation suggested that the VDT workloads were not so heavy and that the effects on each symptom were minor among the subjects of the present survey. However, it is important that consideration be given to ensure that the workloads for workers who operate VDTs every day not be too heavy.

Adult↗
PubMed1993

Fluorescent staining of nucleolar organizer regions for three-dimensional display by confocal laser scanning microscope.

A new method of fluorescent staining of nucleolar organizer regions (F1NORs) is described. Aluminum ammonium sulfate was used instead of silver as the cationic metal ion for binding with NORs-associated proteins, and fluorescent morin was successively bound to aluminum by chelating with modification of the method developed by Malinin (1978). After bleaching the fluorescent staining of NORs by washing water, ordinary AgNORs staining was performed on the same section, and both images of F1NORs and AgNORs were found to coincide with each other. F1NORs staining of human malignant and benign tumors, and colorectal adenomas of borderline malignancy were examined by three-dimensional analysis of the fluorescence images under confocal laser scanning microscope (CLSM). A remarkable increase of F1NORs was found, not only in number but also in volume, with bizarre configuration in the process of tumor progression, and the F1NORs-CLSM technique may be helpful for daily pathological diagnosis of malignancy.

Evaluation Studies as Topic↗
PubMed1993

Early progression stage of malignancy of human colon border-line adenoma as revealed by immunohistochemical demonstration of increased DNA-instability.

The degree of DNA-instability was used as the marker of malignancy and applied to adenoma (7 benign cases and 17 border-line cases) and cancer (8 carcinoma-in-adenoma cases and 17 invasive cancer cases) of human colon. Proliferative activity by PCNA index and the activity of protein synthesis by AgNORs were also estimated for all cases as the supporting markers of malignancy. In all border-line cases, the following findings were obtained: (1), the degree of DNA-instability as revealed by immunohistochemical staining with anti-single-stranded DNA antiserum after acid hydrolysis was increased in border-line adenoma to the level of invasive overt cancer, indicating its malignancy with marked DNA-instability; (2), reflecting the malignant character, abnormal mitosis and single cell necrosis were usually observed in all border-line adenomas by fluorescent Feulgen staining, indicating the DNA alterations; (3), not only the parenchymal but also the stromal PCNA indices were statistically larger in border-line adenoma than in benign adenoma, indicating the "stromal activation" in malignancy; (4), the volumes of AgNORs were much increased in border-line adenoma in comparison with those in benign adenoma, and these showed further increases with the progression of malignancy to the invasive overt cancer. These findings indicate that border-line adenoma of human colon has already malignant character at the early progression stage, although no apparent epithelial atypia, or destructive invasion, is taking place.

Adenoma↗
PubMed1993

[The roles of cytokine in organ-specific tumor metastasis].

The production of cytokines by tumor cells has been suggested as the molecular perturbation responsible for the development of malignant tumors. The behavior of tumor cells in animals is presumed to be affected by these factors, which include such hematopoietic cytokines as GM-CSF, IL-1, and IL-6. Here, we report findings demonstrating that GM-CSF is produced by many murine transplantable tumors with metastatic ability in the lungs, and IL-6 and/or IL-1 are produced by the tumors metastatic in the liver. We discuss the notion that the particular organ or organs in which tumor cells metastasize may be associated with the type of cytokines produced by the tumors. Metastatic spread requires interactions of tumor cells with components of the extracellular matrix of host tissues or with other cells, almost all of which depend on cell surface determinants such as cell adhesion molecules. We also discuss the possibility that the expression and adhesive potentials of adhesive protein (CD44) may be regulated by the cytokine (GM-CSF) excreted from the tumor cells. We then emphasize the possibility that both gene expression of cytokines and adhesive proteins play a critical role in tumor metastasis and in determining organ specificity in metastasis.

Animals↗
PubMed1992

Single- and multiple-dose pharmacokinetics of intravenous cefpirome (HR810) to healthy volunteers.

The safety and pharmacokinetics of single and multiple administrations of cefpirome (HR810), a new cephalosporin antibiotic agent with a broad antibacterial spectrum, were studied in healthy male volunteers. The single administration protocols included a 3-minute intravenous injection of 0.5 g or 1 g, and a 1-hour intravenous drip infusion of 0.5 g, 1 g, or 2 g. The multiple administration protocols included nine intravenous injections and 1-hour intravenous drip infusions of 1 g of cefpirome twice a day at intervals of 12 hours. Cefpirome was tolerated, and only a few mild, subjective and hepatic-function side effects were observed. There were no severe abnormalities. The drug concentrations in the plasma and the urine were determined by means of HPLC and bioassay, and the results correlated well (r = 0.99). The pharmacokinetic parameters were calculated using a two-compartment model. The elimination half-life (t1/2 beta) was about 1.7 hours for both intravenous injection and intravenous drip infusion and was not dose-dependent. AUC and Cmax were dose-dependent in this study, although an accumulation due to multiple administrations was not observed, and there were no changes in the pharmacokinetic parameters after the initial and the final administrations. The recovery rate of the unchanged compound in the urine was more than 80% in the 24 hours after a single administration and was the same after multiple administrations. Bioautography did not show any active metabolites in the plasma or the urine. The results, for safety and pharmacokinetics, show that cefpirome can be expected to have excellent clinical efficacy for bacterial infections.

Adult↗
PubMed1992

Induction of granule release by intracellular application of calcium and guanosine-5'-O-(3-thiotriphosphate) in human eosinophils.

The roles of Ca and G proteins in granule release from human eosinophils were examined by use of a patch-clamp technique in single cells. The morphologic changes and the release of eosinophil peroxidase (EPO) from single cells were simultaneously observed. In addition, the expression of small molecular weight guanine nucleotide binding protein (small G protein) mRNA (smg p25A [rab 3] and smg p21 [rab 1]) was investigated. The intracellular application of Ca, 10 mumol/L, and guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S), 100 mumol/L, induced fusion of EPO containing granules with the surface membrane, which was associated with a marked increase in membrane capacitance. Ca alone caused a rapid granule release at an early stage of cell dialysis, but most granules still remained in a cluster. GTP-gamma-S alone caused a gradual degranulation. Northern blot analysis revealed the definite expression of smg p21 mRNA with no appreciable expression of smg p25A. These results provide direct evidence of granule fusion by intracellular application of Ca and GTP-gamma-S. In addition, Ca dependent proteins and G proteins act cooperatively in granule release, and these proteins likely regulate the different processes of degranulation. Furthermore, a protein, encoded by smg p21, may be involved in the granule release process in human eosinophils.

Calcium↗
PubMed1992

GM-CSF and G-CSF stimulate the synthesis of histamine and putrescine in the hematopoietic organs in vivo.

Histamine and putrescine (a precursor of polyamines) are formed by histidine decarboxylase (HDC) and ornithine decarboxylase (ODC), respectively. Within a few hours after injection of a lipopolysaccharide (LPS) into mice, HDC is induced in the liver, spleen, lung and bone marrow, and ODC is induced in the liver, spleen and bone marrow. Since LPS is known to stimulate the production of various cytokines, the abilities of various cytokines to induce HDC and ODC in the tissues of mice were examined. IL-2, IL-6, IL-8, IFN gamma and M-CSF were ineffective. IL-1 alpha, IL-1 beta, TNF alpha and TNF beta induced HDC and ODC, as does LPS. On the other hand, GM-CSF and G-CSF induced HDC and ODC only in the spleen and bone marrow within a few hours after their injection. These results suggest that, in addition to their roles in inflammation or immune responses, HDC and ODC are also involved in an early stage of hematopoiesis.

Animals↗