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Biomedical subjects

S Baba

Publications and source records attributed to S Baba.

At least 37 records · Page 2Linked to original sources

Alcohol drinking and high blood pressure: data from a 1980 national cardiovascular survey of Japan.

Many epidemiological cross-sectional studies have confirmed that alcohol drinking is related to high blood pressure. However, the impact of alcohol drinking on high blood pressure in the general population including older people has only been reported on in a few studies. The association between alcohol drinking and blood pressure or the prevalence of hypertension was examined using cross-sectional data of 4795 men and 6102 women aged 30-94, randomly selected from the Japanese population in 1980. The response rates were 74 and 84% for men and women, respectively. The prevalence of hypertension adjusted for body mass index (BMI, kg/m2) was significantly higher in everyday male drinkers than in male non-drinkers from the youngest age group (30-39 years) to oldest age group (70 years and over). A relationship between alcohol and blood pressure was found only in the youngest age group (30-39 years) of female drinkers. In each 10-year age-group of men, the BMI-adjusted systolic and diastolic blood pressures in everyday drinkers were 7-10 and 4-6 mmHg higher than those in non-drinkers. The relationship between alcohol and blood pressure in men was confirmed by multiple regression analysis adjusting for age and BMI in both younger (30-59 years) and older (60-94 years) people. The impact of alcohol drinking on blood pressure in men should be taken into account in the primary prevention of blood pressure related diseases and in the treatment of hypertension in both younger and older people.

Adult

Breakdown of hepatic tight junctions during reoxygenation injury.

We investigated whether reoxygenation following anoxia increased biliary permeability and whether or not allopurinol had a protective effect. Isolated rat livers were perfused for 30 min in a one-pass system with buffer equilibrated with 100% nitrogen after stabilization, and then for 60 min with the oxygenated buffer. Hepatic tight junction permeability was assessed by quantifying the early appearance in the bile of horseradish peroxidase (HRP) injected with the perfusate. This early peak represents paracellular passage of HRP, whereas a later second peak results from transcellular passage. In the control livers, 7% of the total HRP passage (93 +/- 50 pg/g liver) was paracellular and 93% was transcellular. After 30 min of reoxygenation following anoxia, however, 516 +/- 20 pg/g liver of HRP passed paracellularly. Addition of allopurinol (5 micrograms/ml) to the perfusate from the start of perfusion reduced paracellular passage of HRP to 219 +/- 49 pg/g liver after anoxia and reperfusion (P less than 0.01). Allopurinol also reduced the cumulative lactate dehydrogenase (LDH) release during the first 30 min of reoxygenation from 2.1 +/- 0.3 x 10(4) to 1.4 +/- 0.4 x 10(4) units/g liver (P less than 0.01). Reduction of the anoxic period from 30 min to 25 min significantly reduced the change in tight junction permeability and the extent of cellular injury: Paracellular passage of HRP was 336 +/- 20 pg/g and LDH release was 0.7 +/- 0.1 x 10(4) units/g liver, both significantly lower than those at 30 min (P less than 0.01). No significant difference in hepatic ATP levels after 60 min of reoxygenation was noted among the experimental groups, but all had lower levels than the control group. The protective effect of allopurinol suggests that the mechanism of biliary reoxygenation injury involves free radical generation. Susceptibility of tight junctions suggests a pattern of injury similar to that involved in anoxic damage of the vascular endothelium.

Adenosine Triphosphate

Cell proliferative activity of epidermal keratinocytes in hair discs.

To clarify the differences in epidermal keratinocyte proliferative activity and in postnatal developmental changes of this activity between the hair discs and the interfollicular epidermis, the incorporation of 3H-thymidine into the nuclei of the basal cells was measured by autoradiography, and the percentages of basal cells thus labelled were calculated. This percentage was higher in hair discs than in interfollicular epidermis at all stages examined. The percentage of labelled basal cells in the hair discs was 10% up to 15 days after birth, decreasing to about 6% from 20 days postnatally. These results suggest that the degree of cell proliferation in the hair disc epidermis differs from that in the surrounding epidermis and that changes in proliferative activity during the postnatal developmental stages are well correlated with the morphogenesis of the hair discs.

Animals

Alpha 1-adrenoceptor subtypes in the rat ventricular muscle.

Scatchard analyses of [3H]prazosin binding in rat ventricular muscle membranes showed biphasic curves, which identified alpha 1High- and alpha 1Low-affinity sites. The alpha 1High-affinity site was completely inhibited by 1 microM phenoxybenzamine. The displacement potencies of alpha 1-adrenergic antagonists were characterized by [3H]prazosin binding to alpha 1High- and alpha 1Low-affinity sites in the absence and presence of 1 microM phenoxybenzamine. The affinities of most chemicals for alpha 1Low-affinity sites were significantly lower than those for alpha 1High-affinity sites, but WB-4101 (2-(2,6-dimethoxy-phenoxyethyl)aminomethyl-1,4-benzodioxane), arotinolol, cinanserin, nifedipine, and p-aminoclonidine had the same affinities for both alpha 1Low- and alpha 1High-affinity sites. These results show that two alpha 1-adrenoceptor subtypes, alpha 1High- and alpha 1Low-affinity, are present in the rat heart, and that there are physical variations in alpha 1-adrenoceptor binding sites, based on their selectivity to antagonists.

Adrenergic alpha-Antagonists

Alpha 1-adrenoceptor subtypes in bovine prostate.

The object of this study was to examine the existence and characteristics of alpha 1-adrenoceptor subtypes in the bovine prostate using the radioligand binding assay method. [3H]Prazosin was used as the radioligand and its binding sites in bovine prostate were classified into two subtypes. One subtype showed a high affinity (alpha 1High, Kd: 101.1 pM and Bmax: 11.8 fmol (mg protein)-1) and the other had a low affinity (alpha 1Low, Kd: 3371.4 pM and Bmax: 50.5 fmol (mg protein)-1). Although the same pKi values of clorethylclonidine, p-aminoclonidine, benoxathian and dibenamine to both alpha 1High and alpha 1Low binding sites in bovine prostate tissue were observed, other alpha 1 antagonists used in this study had different pKi values for the two alpha 1-adrenoceptor subtypes. The existence and binding characteristics of alpha 1-adrenoceptor subtypes in bovine prostate were clarified. It is possible that agents selective for one site may contribute to the development of better drugs for the treatment of bladder outlet obstructions of men with benign prostatic hyperplasia.

Animals

Solubilization of high affinity peptide-YY receptors from porcine brain.

We have previously characterized peptide-YY (PYY) receptors in porcine hippocampal membranes. We demonstrate here that brain PYY receptors can be extracted in the active state using digitonin. Among several detergents tested for their suitability to extract active PYY receptors, digitonin gave the most favorable results, as judged by specific binding of [125I]PYY to the solubilized receptors. The binding of [125I]PYY to digitonin extract was dependent on incubation time, temperature, and protein and magnesium ion concentrations and had a pH optimum of 6-7. Solubilized PYY receptors maintained the rank order of potencies for various related peptides and PYY fragments characteristic of the membrane PYY receptor: PYY greater than neuropeptide Y (NPY) much much greater than avian and porcine pancreatic polypeptide, and PYY greater than PYY-(22-36) much much greater than PYY-(1-22) and PYY-(22-28), respectively. Scatchard analyses of competitive binding data indicated the presence of two classes of binding sites in the digitonin extract; the high affinity component had affinities and binding capacities similar to those of the membrane PYY receptor. Solubilized PYY receptors also retained their sensitivity to guanine nucleotides. PYY was cross-linked to its receptors with disuccinimidyl suberate, solubilized with digitonin, and cross-linked to digitonin-solubilized receptors. The resulting complexes were analyzed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by autoradiography. Using these procedures, we identified a PYY receptor species with a molecular size of 50,000, which was the same size as the labeled protein in native membrane homogenates. Solubilized NPY receptors were also the same size. The solubilized cross-linked PYY receptor was adsorbed by wheat germ agglutinin-agarose and Concanavalin-A, suggesting its glycoprotein nature. These data suggest that the specific binding properties of the PYY receptor are inherent in the solubilized glycoprotein molecules. The solubilization in digitonin of PYY receptors from membranes should allow a more complete molecular and functional characterization of PYY-mediated events and purification of the receptor.

Adsorption

Carbohydrate structures of beta-core fragment of human chorionic gonadotropin isolated from a pregnant individual.

Highly purified beta-core fragment was obtained from urine of a pregnant woman with use of an immunoaffinity column. The amino acid sequence of beta-core fragment indicated that it is composed of two polypeptides linked by a disulfide bond. The two polypeptides correspond to the 6-40 and 55-92 portions of hCG beta-subunit. Both Asn13 and Asn30 residues were glycosylated. The N-linked sugar chains of beta-core fragment were quantitatively released as radioactive oligosaccharides by hydrazinolysis, followed by N-acetylation and NaB3H4 reduction. The radioactive oligosaccharides were fractionated by serial lectin column chromatography and Bio-Gel P-4 column chromatography, and their structures were investigated by sequential exoglycosidase digestion and periodate oxidation. The results indicated that they were a mixture of the four oligosaccharides: Man alpha 1----6(+/- Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(+/- Fuc alpha 1----6)GlcNAc. The structural characteristics of the sugar chains of beta-core fragment are quite different from those of the beta-subunit of hCG whose structures were typical biantennary sugar chains containing the Neu5Ac alpha 2----3Gal beta 1----4GlcNAc beta 1----2 group as their outer chains.

Amino Acid Sequence

Solubilization of the receptors for avian pancreatic polypeptide in chicken, canine, and pig brains.

When n-octyl-beta-D-glucoside was used in several detergents to extract active avian pancreatic polypeptide (APP) receptors, a specific binding of [125I]APP to the solubilized chicken cerebellar and porcine hippocampal membranes was found. The binding of [125I]APP to the solubilized receptors was dependent on incubation time, temperature, and protein concentrations and appeared to have a slightly acidic optimal pH. APP binding to chicken and porcine brain extracts showed a high specificity for APP, although the chicken receptors do not discriminate well between APP and its related peptides, neuropeptide Y and peptide YY. Scatchard analyses of competitive binding data indicated the presence of two classes of binding sites in the brain extracts as in membrane-bound receptors; however, the high affinity component of the chicken receptor showed a decreased affinity after extraction. APP receptors in chicken and porcine brain extracts retained their insensitivity to the nonhydrolyzable GTP analog guanosine 5'-O-(3-thiotriphosphate). Cross-linking studies were performed with the homobifunctional cross-linker disuccinimidyl suberate and brain membrane receptors solubilized with n-octyl-beta-D-glucoside. An APP receptor species with a M(r) of 67,000, the same size as that of the labeled protein in native membrane homogenates of chicken and pig brains, was identified. However, in the canine brain we observed a M(r) 85,000 receptor protein, suggesting that species differences exist among the structures of brain APP receptors. The solubilized cross-linked APP receptors in these species were adsorbed by wheat germ agglutinin-agarose and by concanavalin A, indicating that they are glycoprotein in nature. The availability of the solubilized receptors from vertebrate brains with n-octyl-beta-D-glucoside represents an important step toward the purification and molecular characterization of the APP receptors.

Animals

Evidence for further heterogeneity of the receptors for neuropeptide-Y and peptide-YY in tumor cell lines derived from neural crest.

The expression and structure of the receptors for neuropeptide-Y (NPY) and peptide-YY (PYY) were studied in 16 human and rodent tumor cell lines derived from the neural crest by ligand binding and cross-linking techniques using [125I]Bolton-Hunter-NPY, [125I]PYY, and various forms of monoiodinated NPY and PYY. Although NPY-binding sites were observed in most of the tumor cells, PYY-binding sites were found only on the human neuroblastoma cell lines SMS-MSN, SMS-KAN, SK-N-MC, and MC-IXC and the human Ewing's sarcoma cell line SK-ES. The differential labeling of the NPY/PYY receptors on these cell lines suggests that the NPY/PYY receptors are more heterogeneous than previously described as the Y1, Y2, and Y3 receptor subtypes. Cross-linking studies demonstrate that the Y1 and Y2 receptors for NPY/PYY are structurally different (mol wt, 70 and 50 kilodaltons, respectively) and that the 70- and 50-kilodalton receptor proteins are coexpressed in certain tumor cell lines. This could explain at least in part why cell lines show a relative specificity for Y1/Y2 classification, observed as the inhibition by both C-terminal fragments and Y1-specific analogs on the NPY/PYY binding to membrane receptors. Collectively, the present study suggests further heterogeneity of the NPY/PYY receptors and the existence of multiple receptor proteins in the tumor cell lines derived from the neural crest.

Animals

[A report of two cases of cervical necrotizing soft-tissue infection].

Two recent cases of cervical necrotizing soft-tissue infection are herein presented. Case 1. A 52-year-old man with uncontrolled diabetes was hospitalized because of an erythematous swelling of the left side of his neck and high grade fever. Fetid yellowish pus exuded from the left parotid area. The swelling extended from the left temporal area to the left supraclavicular fossa, with necrosis of the parotid gland, sternocleidomastoid, masseter and a portion of the strap muscles. Wound cultures revealed Staphylococcus aureus and alpha-hemolytic streptococcus. No anaerobic bacteria were detected. Treatment consisted of intravenous administration of antibiotics, control of diabetes with insulin, and debridement of the necrotic tissue, which left an epidermal defect in the initially swollen area. Transfer of a forearm free flap was done after the growth of healthy granulation tissue over the affected area. Case 2. A 55-year-old woman with rheumatoid arthritis was transferred to our hospital after tracheotomy performed in another hospital because of dyspnea due to severe crepitant swelling of her cheeks and submandibular areas bilaterally, and her left temporal area. A copious amount of fetid pus exuded from the incisions made in the left temporal area, left cheek, and right submandibular area. There were bilateral diffuse rales. Culturing the pus revealed alpha-hemolytic streptococci, while MRSA and Pseudomonas aeruginosa were detected from cultures of sputum. No anaerobic bacteria were found. After intravenous administration of antibiotics, infected wounds and pneumonia were ameliorated, and necrotic subcutaneous tissue and fascia were debrided. The patient was discharged with a residual depression in her left cheek and a scar on her left temporal area.

Connective Tissue Diseases

[Studies on the production of endogenous cytokines in patients with renal cell carcinoma].

This study was undertaken to determine the production of tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) by biological response modifier (BRM) in patients with renal cell carcinoma (RCC). Peripheral blood mononuclear cells (PBMC), which were donated from thirteen patients with RCC and five healthy controls, were cultured with streptococcal preparation, OK432, and/or macrophage-colony stimulating factor (M-CSF), and the TNF levels and IFN-gamma levels in the supernatant were evaluated. TNF activities were assayed by cytotoxicity to L929 cells and IFN-gamma activities were measured by inhibition of the cytopathic effects of sindbis virus on FL cells. The highest levels of TNF in the supernatant were 235.4 +/- 96.0 U/ml/1 x 10(4) cells in patients with renal cell carcinoma and 251.6 +/- 71.8 U/ml/1 x 10(4) cells in healthy controls, which were noted at 12 hours of incubation with the concentration of OK432 adjusted to 0.05 KE/ml. There was no statistically significant difference between the TNF activities induced by in vitro culture of PBMC obtained from patients with renal cell carcinoma and those from healthy controls. The production of TNF by in vitro culture of PBMC with OK432 of 0.05 KE/ml was augmented by adding 100 U/ml M-CSF especially at 48 and 72 hours of incubation, whereas M-CSF alone did not stimulated TNF production. The medium levels of IFN-gamma in six different cultures of PBMC with 0.05 KE/ml OK432 at 12, 24 and 48 hours of incubation were 1.15 +/- 0.34 U/ml/l x 10(4) cells, 2.23 +/- 0.93 U/ml/l x 10(4) cells, and 7.83 +/- 4.00 U/ml/l x 10(4) cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Localized proliferative effect of preadipocytes on cultured human epidermal keratinocytes.

The effect of preadipocytes (ST 13) on cultured normal human epidermal keratinocytes (NHEK) was investigated. The growth of NHEK was accelerated with co-cultured ST 13 cells. This stimulative effect must have been localized around viable ST 13 cells, because neither the medium nor the surface conditioned by ST 13 or the ST 13 cell fragments showed any promotion of NHEK growth, and NHEK showed a compact, paving-like arrangement only when they were attached directly to ST 13 cells. It became clear that these compactly arranged keratinocytes have an active proliferative ability, since their nuclei showed a marked uptake of 5-bromodeoxyuridine (BrdU) and they were positively stained with anticytokeratin 37, a monoclonal antibody against the basal epidermis. Under electron microscopy, ST 13 preadipocytes were closely connected with NHEK. These results, together with those of previous reports, suggest that the localized proliferative effect of ST 13 cells on NHEK is due to cell-to-cell contact.

Adipose Tissue

[A study of intraoperative rapid frozen section diagnosis focusing on accuracy and quality assessment].

Accuracy of frozen section (FS) diagnoses was investigated in a consecutive series of 1129 intraoperative consultations. In our series, the correct diagnosis including clinically not serious minor errors was made in 96.9% of the cases. Whereas the accuracy ratio of FS diagnosis for unknown pathologic process decreased to 92.2%. Among all the types of tissues, central nervous system was shown to be the most frequently handled for FS, followed by lung/bronchus, breast, liver/biliary tract, lymph node and so forth. The requesting ratio of FS, on the other hand, tended to be high in the following specialties; neurosurgery (46.5%), thoracic surgery (19.0%), general surgery, (10.0%). Deferred diagnosis with a provisional diagnosis and misinterpretations in histology typing without serious clinical problem accounted for 2.7% and 3.1% respectively. Causes of erroneous diagnoses seemed to be multifactorial, such as inappropriate sampling, diagnosis on poor quality histology sections, lack of clinical information, lack of enough experience in FS practice of pathologists, or a combination of more than two of them, though inevitable cases showing minimal cytological and structural atypia were included. Intraoperative consultation by FS diagnosis is now essential to serve a good quality medication to patients. It is thus necessary that to establish a tight peer review system and also to provide an education program with regard to practice in FS diagnosis particularly for young pathologists.

Frozen Sections

Poly (lactic/glycolic acid) microspheres containing antigen as a novel and potential agent of immunotherapy for allergic disorders.

In order to establish a safer and simpler antigen administration method in immunotherapy, we prepared biodegradable microspheres containing antigen and evaluated its safety and efficacy using guinea pigs. Poly (lactic/glycolic acid); (LGA) microspheres containing ovalbumin (OA) were fabricated by solvent evaporation. Over 70% of the OA was released from the microspheres within 3 days, and release was completed within 14 days in vivo. The local tissue reactions to the OA-LGA microspheres were apparently weaker than those to OA-alum. Repeated injections of high dose OA-LGA microspheres to OA-sensitized guinea pigs (high-LGA group) for 8 weeks at intervals of 2 weeks elicited an excellent therapeutic effect, i.e. a significant increase in the threshold value of antigen inhalation test, with a significant increase in IgG2 blocking antibody. The therapeutic efficacy of the high-LGA group was comparable to the conventional immunotherapy model (conventional group) and was superior to the antigen-alum model (alum group). We concluded that administration of antigen-LGA microspheres could become a new immunotherapeutic method for allergic disorders, being safer and requiring a lower frequency of antigen injections than the conventional method.

Animals