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Biomedical subjects

M Kawata

Publications and source records attributed to M Kawata.

At least 181 records · Page 10Linked to original sources
PubMed1990

[Application of gastric acidity-controlled beagle dog to bioavailability study of cinnarizine].

The relationship between gastric acidity and bioavailability of a weakly basic drug, cinnarizine (CN) was investigated in the gastric acidity-controlled beagle dogs. The dissolution of CN from capsules was very fast at pH 1.2 but it decreased with an increase in pH. The capsules containing CN were orally administered to the beagle dogs of the following three groups: 1) the dogs whose gastric acidity were not controlled; 2) the dogs whose gastric acidity were controlled to high levels (less than pH 2) with pentagastrin; 3) the dogs whose gastric acidity were controlled to low levels (more than pH 6) with omeprazole. The peak plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC0-8h) of CN were most variable in the first group. On the other hand, the variations of these parameters were small in the second and third groups. The Cmax and AUC0-8h of CN in the high acidity group were about 20 times larger than those in the low acidity group (p less than 0.01). The bioavailability of CN was markedly influenced by the gastric acidity. This finding was similar to that in human subjects. The gastric acidity-controlled beagle dogs are useful animal models to evaluate the bioavailability of weakly basic drugs such as CN, exhibiting pH-dependent dissolution behavior.

Animals↗
PubMed1990

Effect of hypertonic saline on the corticotropin-releasing hormone and arginine vasopressin content of the rat pituitary neurointermediate lobe.

The changes in the levels of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in the neurointermediate lobe of the pituitary (NIL) following hypertonic saline administration were examined in rats. The plasma osmotic pressure in rats receiving 2% NaCl for 8 days was greatly increased. Plasma AVP concentration in rats receiving 2% NaCl for 8 days were significantly higher than in control rats (566% of the control level). Plasma corticosterone was significantly higher in the saline-treated rats than in controls, whereas plasma ACTH was not significantly different. The pituitary ACTH concentration was much higher in the saline-treated rats than in controls. CRH in the NIL was increased significantly by saline treatment (419% of the control concentration), whereas the CRH in the paraventricular nucleus and median eminence of control and saline-treated rats did not differ significantly. The AVP in the NIL fell greatly in saline treated rats. The extract from both control and saline-treated rats showed a major peak for immunoreactive CRH, with a retention time identical to that of rat CRH. However, the peak was much higher in the extract from saline-treated rats. The immunoreactive AVP peak was greatly reduced in saline-treated rats. These results suggest that hypertonic saline administration increases the CRH in the NIL and causes AVP hypersecretion and/or hyperfunction of magnocellular-NIL CRH might be responsible for pituitary-adrenal stimulation in saline-treated rats.

Adrenal Cortex Hormones↗
PubMed1990

Effects of hyperosmotic stimulation and adrenalectomy on vasopressin mRNA levels in the paraventricular and supraoptic nuclei of the hypothalamus: in situ hybridization histochemical analysis using a synthetic oligonucleotide probe.

The effects of salt loading and adrenalectomy on arginine vasopressin (AVP) mRNA levels in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) of the hypothalamus were studied by semiquantitative in situ hybridization histochemistry, using a synthetic oligonucleotide probe and a computer-assisted image analysis system. Salt loading (2% NaCl) for 7 days produced marked increases in AVP mRNA levels in the magnocellular neurons of the PVN, SON, and accessory nuclei. Adrenalectomy caused an increase in AVP mRNA expression in the magnocellular part of the PVN and the expansion of hybridization signals into its medial parvocellular region, where the cell bodies of corticotropin-releasing hormone (CRH) neurons are located. No apparent alteration of AVP mRNA levels was observed in the SON following adrenalectomy. These results indicate that hyperosmotic stimulation and the loss of circulating glucocorticoids had differential effects on AVP gene expression in the PVN and SON, and that the magnocellular PVN and SON neurons responded in different manners to the loss of feedback signals.

Adrenalectomy↗
PubMed1990

[Analysis of the denture dynamics in R.P.D.'s. 2. Influence of retainers on the dynamics of free-end-saddle].

The ordinary denture movement during function is defined as the "Denture dynamics" in R.P.D.'s. by K. H. Körber (1975). The Author has already reported the evaluating method of the denture dynamics objectively by two ways: The displacement sensors of magnetoresistors detected the vertical and horizontal movements of denture saddle in free end situation. Tiny accerelometer also detected the accerelation during the movements. In this present study, the correlations among the retainers used, the extent of the denture dynamics in displacement and accerelation, the occluding force and the abutment tooth mobility induced by the denture support were correlatively evaluated in two patients with class I free end R.P.D.'s. with interchangeable retainers by above methods. All the data were collected simultaneously by the electronic measuring and recording apparatus. Following results were obtained: 1. The denture dynamics depended on the selection of retainers examined. The extent of the dynamics reduced from the denture with the wrought wire clasps, the denture with the cast clasps, then to the denture with cone crown telescopes in sequence. 2. The occluding force increased just as the changes in sequence of the denture dynamics. 3. The abutment tooth moved to the distal in each case. The highest value of the mobility was found in the denture with the cast clasps, then in the denture with the wrought wire clasps. The least value of the tooth mobility was found in the denture with the cone crown telescopes. These results will strongly support the concept of the free end saddle R.P.D.'s anchored and supported rigidly by the abutments and the residual ridges in clinics.

Dental Abutments↗
PubMed1990

[Cell biological characteristics of a human embryonal carcinoma cell line].

We examined the cell biological characteristics of a human embryonal carcinoma cell line. NEC 14, derived from a male germ cell tumor of testis origin. The following results were obtained. 1) The morphological characteristics of NEC 14 cells were small size, an increase in the N/C ratio and poor development of organelle and desmosome-like cell-cell junctions. The NEC 14 cells proliferated rapidly and the population doubling time in vitro was 17 hours. 2) The functional characteristics of NEC 14 cells were the localization of intermediate filaments such as keratin and vimentin, hCG secretion and tissue plasminogen activator and laminin synthesis and expression of cell surface antigens such as stage-specific embryonic antigen-3, trophoblast antigen and neuron cell surface antigen. 3) The mode of chromosome number was 58 and many abnormal and undetermined chromosomes were found in the NEC 14 cells. 4) Differentiation was observed in vitro and in the tumor tissues xenotransplanted into nude mice.

Antigens, Surface↗
PubMed1989

Identification of a major GTP-binding protein in bovine aortic smooth muscle membranes as smg p21, a GTP-binding protein having the same effector domain as ras p21s.

At least two GTP-binding proteins (G proteins) with Mr values of about 20,000 were extracted from bovine aortic smooth muscle membranes by sodium cholate. The most abundant G protein (22K G) was purified to near homogeneity by successive column chromatographies of Ultrogel AcA-44, phenyl-Sepharose CL-4B, hydroxyapatite and Mono Q HR5/5. 22K G showed kinetic and physical properties very similar to those of smg p21, a G protein recently isolated from bovine brain and human platelet membranes, having the same effector domain as ras p21s. Moreover, 22K G was recognized specifically by the anti-smg p21 antibody. These results indicate that the major G protein in bovine aortic smooth muscle membranes is smg p21.

Animals↗
PubMed1989

Phosphorylation of smg p21, a ras p21-like GTP-binding protein, by cyclic AMP-dependent protein kinase in a cell-free system and in response to prostaglandin E1 in intact human platelets.

We have separated multiple small Mr GTP-binding proteins (G proteins) from bovine brain membranes by several column chromatographies and purified to near homogeneity four of them, including a novel Mr 24,000 G protein (smg p25A), a novel Mr 22,000 G protein (smg p21), the rho protein (rho p20), and the c-Ki-ras protein (c-Ki-ras p21). Among these small Mr G proteins, only smg p21 is phosphorylated stoichiometrically by cAMP-dependent protein kinase (protein kinase A), and c-Ki-ras p21 is phosphorylated to a small extent by protein kinase A in a cell-free system. None of smg p25A, rho p20, and other partially purified small Mr G proteins is phosphorylated by protein kinase A. Neither smg p21 nor other small Mr G proteins are phosphorylated by protein kinase C. About 1 mol of phosphate is maximally incorporated into 1 mol of smg p21 by protein kinase A. Only serine residue(s) are phosphorylated. The guanosine 5'-3-O-(thio) triphosphate (GTP gamma S)-bound and GDP-bound forms of smg p21 are phosphorylated with the same reaction velocity. The phosphorylation of smg p21 affects neither its GTP gamma S-binding nor GTPase activity. smg p21 is found in human platelets, and this human platelet smg p21 is also phosphorylated by protein kinase A at the same site(s) as bovine brain smg p21 in a cell-free system. When intact human platelets are stimulated by prostaglandin E1 known to elevate the cAMP level, four proteins with apparent Mr values of 240,000, 50,000, 24,000, and 22,000 are phosphorylated. These four proteins are also phosphorylated by the action of dibutyryl cAMP but not by the action of thrombin, Ca2+ ionophore A23187, or 12-O-tetradecanoylphorbol-13-acetate. Among the four proteins, the Mr 22,000 protein is identified as smg p21. The site(s) of phosphorylation of smg p21 by protein kinase A in a cell-free system are identical to that phosphorylated in response to prostaglandin E1 in intact platelets. These results indicate that among many small Mr G proteins, smg p21 is selectively phosphorylated by protein kinase A and that this G protein is also phosphorylated by this protein kinase in response to prostaglandin E1 in intact human platelets.

Alprostadil↗
PubMed1989

Does acute, intense stimulation of oxytocin neurones in the supraoptic nucleus increase their content of oxytocin mRNA?

We investigated whether a sustained increase in oxytocin secretion, with or without enhanced electrical activity of the cell-bodies of oxytocin neurones, leads to a rapid increase in oxytocin mRNA content in these neurones. To stimulate oxytocin release, naloxone (2.5 mg/kg i.v. twice, 30 min apart) was given to urethane-anaesthetized female rats after intracerebroventricular (i.c.v.) morphine or vehicle infusion for 5 days; in the latter, naloxone acts on the neurohypophysis to increase oxytocin release without affecting the electrical activity of oxytocin neurone cell-bodies, but in the former, naloxone acts both on the neucohypophysis and on the cell-bodies to excite them electrically. Oxytocin content in peripheral plasma was measured intermittently by radioimmunoassay for 4 h after i.v. naloxone or vehicle, then the brain was removed and cryostat sections were cut through the supraoptic nucleus (SON). Oxytocin mRNA content in individual neurones (25-50 per rat) was measured semiquantitatively by in situ hybridisation histochemistry, using a tritiated synthetic cDNA 25-mer oligonucleotide probe, autoradiographical visualisation, and computer-assisted image-analysis to measure silver grain density. Nalaxone increased oxytocin content in plasma 7-fold for at least 40 min in i.c.v. vehicle-infused rats, and 40-fold for at least 40 min in i.c.v. morphine-infused rats. Naloxone had no significant effect on the oxytocin mRNA content in labelled cells in the SON, and no effect on the proportion of labelled cells, in either the i.c.v. morphine- or i.c.v. vehicle-infused rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Brain natriuretic peptide in the porcine spinal cord: an immunohistochemical investigation of its localization and the comparison with atrial natriuretic peptide, substance P, calcitonin gene-related peptide, and enkephalin.

Immunohistochemistry was used to localize brain natriuretic peptide in the porcine spinal cord and to compare it with that of atrial natriuretic peptide, substance P, calcitonin gene-related peptide and [Met]enkephalin. Brain natriuretic peptide-immunoreactive varicose fibers were observed in lamina I and the inner portion of lamina II of the dorsal horn. Semiquantitative analysis showed that the highest density of brain natriuretic peptide-immunoreactive varicosities was in the lumbosacral and coccygeal segments. The distributional pattern of brain natriuretic peptide-immunoreactive nerve fibers in the spinal cord was unique and quite distinct from that of the other neuropeptides studied. These neuroanatomical findings suggest that brain natriuretic peptide may play a role in the regulation of nociceptive processing in the spinal cord, either alone or with bioactive substances.

Animals↗
PubMed1989

Implication of activation of intraperitoneal macrophages with bio-degradable microspheres.

To estimate the possibility that biological degradable starch microspheres (DMS) activate abdominal or intraperitoneal macrophages (IMP), two sizes of DMS (Spherex, Pharmacia, Sweden) were injected into the peritoneum of the ICR mice of 4 to 8 weeks of age. Three days after the injection, peritoneal fluid was collected and incubated for one hour at 37 degrees C under 5% CO2. The cells which adhered to the petri dish were IMP, to which DMS was added for 18 hrs. The cultured IMP were observed by scanning electron microscope (SEM) and the ratio of the active type to the total number of IMP was counted as an index of the effect of DMS to IMP. The activation effect of DMS on the incubated IMP was significant in the group which was cultured with 2 microns DMS after the 45 microns DMS injection. That indicated the possible DMS function as a potential IMP activating factor (MAF).

Animals↗
PubMed1989

Neuron-specific enolase as a serum marker for immature teratoma and dysgerminoma.

Neuron-specific enolase (NSE) was measured with an enzyme-immunoassay in sera from 54 patients with malignant (24 cases) and benign (30 cases) germ cell tumors of ovarian origin. Serum NSE contents were clearly raised above control value (greater than 10 ng/mg) in 4 of 8 patients with immature teratomas and 5 of 6 with dysgerminomas. NSE was also measured in nine cell lines of germ cell tumors. Among these cell lines, high NSE contents were detected in the cell extracts and culture supernatants from PA-1 and Tera-II lines. In immunohistochemical study, widespread positive staining for NSE was shown in dysgerminomas, whereas the immunostaining was confined to neural elements in both an immature teratoma and xenograft tumors derived from PA-1 and Tera-II lines in nude mice. These findings suggest that serum NSE measurements are of diagnostic value not only for immature teratomas but also for dysgerminomas.

Biomarkers, Tumor↗
PubMed1989

Milky spots in the human greater omentum. Macroscopic and histological identification.

Macroscopic and histological investigations were made from surgical specimens demonstrating milky spots in the human greater omentum from subjects of various ages. The milky spots in the human greater omentum appear as tiny, cotton-wool-like masses to the naked eye. Histologically, the milky spots consisted mainly of many macrophages with diffuse cytoplasmic esterase reaction products and esterase-negative B lymphocytes surrounding the vascular networks. Macrophages phagocytosed many carbon particles which were introduced as a carbon suspension during the operation. The vascular networks were blood capillary convolutions with a glomerular shape. Silver impregnation showed the delicate networks of reticular fibers which constitute the framework of the organ. The number of milky spots was highest in infancy and gradually decreased with age.

Adolescent↗
PubMed1989

Preparation and pharmacokinetic and pharmacodynamic evaluation of hydroxy propyl cellulose-ethyl cellulose microcapsules containing piretanide.

Hydroxy propyl cellulose (HPC)-ethyl cellulose (EC) microcapsules containing piretanide were newly by a solvent evaporation technique and their slow-release properties were evaluated on dissolution properties in vitro and pharmacokinetic and pharmacodynamic parameters in beagle dogs. The dissolution behavior of piretanide from the microcapsules in dissolution media of pH 1.2-6.8 and the plasma piretanide level in beagle dogs varied dependently on the contents of HPC and EC. As compared with ordinary piretanide tablet on the market, the HPC-EC10 (5:3) microcapsule showed the controlled dissolution behavior, sustained plasma piretanide level, almost same AUC (area under curve), slow urinary piretanide excretion, decreased urine excretion maximum rate, and no difference in the cumulative urine volume and cumulative urinary electrolytes (Na+, K+, Cl-) excretion. HPC-EC microcapsules containing piretanide sufficiently satisfied the conditions which slow-release preparations must have.

Animals↗