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Biomedical subjects

M Ichikawa

Publications and source records attributed to M Ichikawa.

At least 235 records · Page 13Linked to original sources

Renal nerves contribute to salt-induced hypertension in sinoaortic-denervated uninephrectomized rabbits.

The objective of this study was to investigate the role of the renal nerves in the pathogenesis of salt-induced hypertension in sinoaortic-denervated uninephrectomized rabbits. Twelve rabbits were divided into two groups. Sinoaortic-denervated uninephrectomized rabbits with intact renal nerves (sham group: n = 6) and without renal nerves (RDN group; n = 6). In both groups, 2 days of 154 meq/l NaCl loading was followed by 10 days of 1,700 meq/l NaCl loading. We administered 154 meq/l or 1,700 meq/l NaCl intravenously at every 8 h. Serial changes in mean arterial pressure (MAP) and heart rate (HR) were recorded using a microcomputer system. We chronologically measured hematocrit, serum osmolality, serum sodium, potassium, and chloride concentration, serum creatinine, plasma renin activity, plasma aldosterone, plasma norepinephrine, plasma arginine vasopressin, and plasma atrial natriuretic peptide. Urine volume and body weight were recorded every day, as were urinary concentrations of sodium, potassium, and chloride. The basal value of MAP in the sham group was significantly higher than that in the RDN group (on day -2, 111 +/- 1 mmHg for sham, 99 +/- 2 for RDN, P less than 0.001). Hypertonic saline loading induced an elevation of blood pressure in the sham group (126 +/- 2 mmHg on day 4, 127 +/- 2 on day 7, 124 +/- 4 on day 10). There were no significant changes in the response to salt loading in the RDN group. In the sham group, the retention of sodium was significant compared with that in the RDN group on day 5, and this difference was maintained until the end of the experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Alexithymia and depression in families with alcoholics.

Alexithymia and depression in family members of alcoholics were examined among 48 families. Results were as follows: (1) The prevalence of alexithymia was 47.9% (23 cases), whereas that of depression was only 6.3% (3 cases); (2) no significant correlation between alexithymia and depression was noted; (3) expressiveness and conflict were significantly lower in families with alcoholics than in healthy families without alcoholics, although families with alcoholics do have strong conflicts. The results suggest the possibility that half of them forcefully suppress their conflicts, unconsciously deny the existence of alcoholics, and finally manifest secondary alexithymia.

Adult↗

Effects of antihypertensive agents on arterial baroreceptor reflexes in conscious rats.

The effects of antihypertensive treatment with four currently used agents (trichlormethiazide, atenolol, nicardipine, and enalapril) on the arterial baroreceptor reflex control of renal sympathetic nerve activity and heart rate were investigated in 45 conscious spontaneously hypertensive rats and 37 age-matched Wistar-Kyoto rats. Antihypertensive agents were administered for 2 weeks beginning at 8 weeks of age to treat and prevent the development of hypertension. Blood pressure was reduced to a similar level (-13 +/- 3 mm Hg, p < 0.05) by each antihypertensive agent. Blood pressure, heart rate, and renal sympathetic nerve activity were recorded in the conscious state during phenylephrine and nitroglycerin ramp infusion. The gain in the baroreceptor reflex was determined from the maximum slope of logistic function curves. Untreated spontaneously hypertensive rats exhibited decreased sensitivity of reflex control of renal sympathetic nerve activity and heart rate (-1.78 +/- 0.07% of control/mm Hg and -2.16 +/- 0.05 beats per minute/mm Hg, respectively) compared with untreated Wistar-Kyoto rats (-3.62 +/- 0.18% of control/mm Hg, p < 0.01, and -3.46 +/- 0.11 beats per minute/mm Hg, p < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Subcellular localization of xanthine oxidase in rat hepatocytes: high-resolution immunoelectron microscopic study combined with biochemical analysis.

Xanthine oxidase (XO), a molybdo-flavoprotein enzyme involved in purine degradation, was localized immunocytochemically in rat hepatocytes by high-resolution immunoelectron microscopy. XO was isolated from rat liver and a 150 KD polypeptide was purified. Antibodies were raised in rabbits. Small pieces of fresh liver were quickly frozen by contact with a copper block pre-cooled with liquid helium and were freeze-substituted with either 2.5% OsO4 or 0.2% glutaraldehyde in acetone. They were then warmed and embedded in Epon-Araldite or Araldite 6005. Resin sections were treated by indirect immunostaining using anti-rat liver XO antibody and protein A-gold. The labeling pattern was clearly over the cytosol and not on cell organelles. A few gold particles were found over the mitochondrial matrix, but not over the endoplasmic reticulum, Golgi apparatus, lysosomes, or peroxisomes, including their crystalloid core. These results are consistent with those of the biochemical assay of XO in this study. The significance of the occasional immunolabeling of the mitochondrial matrix remains obscure, since biochemical determinations in this study indicate no XO activity in the mitochondrial fraction.

Animals↗

Synthesis of dibenzoylmethane derivatives and inhibition of mutagenicity in Salmonella typhimurium.

Twenty dibenzoylmethanes with methyl, methoxy, bromo, chloro, or fluoro substitution on either one or both benzene rings were synthesized and assayed for inhibition of the mutagenicity of 2-nitrofluorene in S. typhimurium TA98. 2,2-Dimethoxy, 3,3-dimethoxy and 3,3,4,4-tetramethoxydibenzoylmethane was as active as dibenzoylmethane. None of the halogen-substituted dibenzoylmethanes were active. These results demonstrate that dibenzoylmethanes can inhibit the mutagenicity of 2-nitrofluorene, and that modifications made on the benzene rings of dibenzoylmethane cannot enhance the antimutagenicity of this parent compound.

Antimutagenic Agents↗

Thyroid papillary adenocarcinoma in a woman with Peutz-Jeghers syndrome.

We present a rare case of Peutz-Jeghers(P-J) syndrome in a 29-year-old woman who developed adenocarcinoma of the thyroid and polyps in the gastrointestinal tract. Polyps removed from the stomach, colon and ileum showed features typical of hamartomas. Histological examination indicated that the tumor resected from the right lobe of the thyroid was a papillary adenocarcinoma. This appears to be the first precise report of a P-J syndrome associated with thyroid carcinoma. This case adds an example of predisposition of P-J syndrome to extra-intestinal malignancy and indicates the importance of long-term observation of malignancy.

Adenocarcinoma, Papillary↗

Abscess within a glioblastoma multiforme--case report.

A rare case of abscess within a glioblastoma with an unusual presentation occurred in a 46-year-old female who developed right hemiparesis and seizure. Computed tomography and magnetic resonance imaging demonstrated hemorrhage which mimicked hemorrhagic infarction. However, the lesions developed ring enhancement. Aspiration showed one to be an abscess, which collapsed by drainage but later re-expanded. The mass was removed, and histological examination revealed glioblastoma.

Brain Abscess↗

[Treatment of hemobilia after percutaneous transhepatic cholangiography and drainage (PTCD)].

PTCD was performed in 206 of our patients during the past 6 years and 7 months. Of the 206, hemobilia occurred in 14 patients (6.8%). The hemorrhage was completely stopped by irrigation of the bile duct in 3 patients, compression with a larger catheter in 7 patients, and transcatheter anterior embolization (TAE) in 4 patients. TAE was performed on the patients whose hemobilia could not controlled by the compression with a larger catheter. In TAE, either a steel coil or a sponge was used as an embolus. Rebleeding occurred in one patients for whom the right hepatic artery was chosen as a embolization site. Therefore, it was decided that the embolization was going to be done in all the hepatic arteries when the blood stream in the portal vein and preserved functions of the liver of the subjected patients including the one with rebleeding were fully normal. A complete control of the hemorrhage was obtained in all patients. The PTCD root caused hemobilia was removed after TAE in considering the possibility of rebleeding from the root, and a new PTCD root was made.

Aged↗

Glycosylation of P-glycoprotein in a multidrug-resistant KB cell line, and in the human tissues.

P-glycoprotein (P-gp) is thought to transport anti-cancer drugs and to be responsible for the multidrug-resistant (MDR) phenotype. Immunohistochemistry reveals that P-gp is also expressed in normal human tissues, such as the adrenal gland, kidney, liver, and the capillary endothelium of the brain and testis. However, little is known about the structural and functional variations of P-gp in these tissues. With immunoblotting and photoaffinity labeling, we found that the molecular mass of P-gp in these tissues varied between 130-140 kDa. To clarify the post-translational modification of P-gp, we studied the biosynthesis of P-gp in a human multidrug-resistant cell line (KB-C2). We found that P-gp was produced in KB-C2 cells as a 125 kDa precursor and was slowly processed (t1/2 = 45-60 min) to the mature form of 140 kDa. In the presence of tunicamycin, a 120 kDa form of P-gp was synthesized and this form was no longer processed. Treating the 125 kDa precursor form with endo-beta-N-acetylglucosaminidase H (Endo H) and the 140 kDa mature form with N-glycanase diminished the molecular size of P-gp to that of the tunicamycin-treated form. N-Glycanase almost completely removed [3H]glucosamine labeling from P-gp. These data indicate that the major modification of P-gp is N-linked glycosylation. P-gps from KB-C2 cells, kidney and adrenal gland had a different lectin-binding capacity. There seems to be a variety of N-linked glycosylations in tissue and tumor P-gps.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Ultrastructure of the ganglion cells of the terminal nerve in the dwarf gourami (Colisa lalia).

In our previous light microscopic studies (Oka et al., Brain Res. 367: 341-345, '86; Oka and Ichikawa, J. Comp. Neurol. 300: 511-522, '90), we reported that there are at least two types of terminal nerve (TN) cells based on cell size and immunoreactivity: type I cells had large cell bodies, while type II cells had smaller cell bodies. Type I TN cells were immunoreactive to gonadotropin-releasing hormone (GnRH) and may be the major source of GnRH-immunoreactive fibers that are widely distributed throughout the brain. Type II TN cells, on the other hand, were not immunoreactive to GnRH. In the present paper, we examined the cytology and synaptology of these two types of TN cells with electron microscopy. Type I TN cell bodies were found to have morphological characteristics similar to those of other peptide-synthesizing neurons and are likely to be actively synthesizing GnRH. The frequent occurrence of coated vesicles close to the plasma membrane of the cell body was suggestive of membrane retrieval following exocytosis of the vesicular contents from the cell surface. Neighboring TN cells were either in direct juxtaposition with one another or made specialized "glomeruloid" cell-to-cell contacts; these specializations may be relevant for nonsynaptic intercellular communications among the TN cells. Within these glomeruloid complexes, the somatic processes of TN cells received inputs from two types of synaptic terminals: one containing only spherical synaptic vesicles and another containing a small number of dense-cored vesicles in addition to the spherical synaptic vesicles. Axosomatic synapses were rare on type I TN cell bodies. In contrast, type II TN cell bodies had morphological characteristics similar to those of neurons in other brain regions. These receive axosomatic inputs from synaptic terminals containing only spherical synaptic vesicles and those with a small number of dense-cored vesicles in addition to the spherical synaptic vesicles. Thus, each type of TN cell has unique fine structural characteristics which may correlate to their different functional roles.

Animals↗

Interaction of organic chemicals with P-glycoprotein in the adrenal gland, kidney, and a multidrug-resistant KB cell.

P-glycoprotein (P-gp) is thought to mediate the transport of anti-cancer drugs and to be responsible for the multidrug-resistant (MDR) phenotype in tumor cells. However, the function of P-gp in normal tissues is still not well understood. We present evidence indicating that the active efflux of several structurally unrelated organic compounds is mediated by P-gp in multidrug-resistant KB (KB-C2) cells and that these compounds interact with P-gp in the kidney and adrenal gland. The photoactive radioactive calcium channel blocker [3H]azidopine labels a protein of approximately 140 kDa in crude membrane fractions from human kidney and adrenal gland and a 130-kDa protein from bovine adrenal gland. These photolabeled proteins are immunoprecipitated with an anti-P-gp antibody. Photolabeling is inhibited by vinblastine, reserpine, and several other organic chemicals. These data indicate that the kidney and adrenal gland express P-gp (or a protein closely related to P-gp) that can interact with several organic compounds and that the P-gp expressed in these tissues has a drug-binding site similar to that of P-gp in KB-C2 cells. Our findings thus strongly support the hypothesis that P-gp can transport a wide variety of organic chemicals as well as anti-cancer drugs and that one of the physiological functions of P-gp is the excretion of certain classes of organic compounds.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Functional p75 interleukin-2 receptor expression on the fresh blast cells in childhood acute lymphoblastic leukemia with natural killer cell properties.

Neoplastic cells of childhood acute lymphoblastic leukemia (ALL) with natural killer (NK) cell properties were studied for the expression of p75 interleukin-2 receptors (IL-2R) and the receptor functions. Freshly prepared blast cells from a patient with ALL had NK cell properties: (1) the phenotype such as CD56+, CD2+, E-rosette+, CD3-, and CD19-; and (2) the presence of spontaneous cytotoxicity against NK-sensitive K562 target cells. Although p55 Tac antigen was not detectable, there was the expression of p75 IL-2R on the freshly prepared blast cells: 70% of the cells reacted with Mik-beta 1 monoclonal antibody against p75 IL-2R as determined by flow cytometry. Two-color flow cytometry revealed that the blast cells expressed both p75 IL-2R and NKH-1. NK activity of the blast cells was augmented by their treatment with 1,000 U/ml recombinant IL-2 (rIL-2): the cytotoxicity level as percentage lysis increased to 38.7% from 22.0% when the normal lymphocyte value increased to 62.1% from 46.2%. Although the blast cells possessed no apparent level of proliferative capacity, the addition of 1,000 U/ml rIL-2 yielded a 2.7-fold increase in their thymidine uptake. These results demonstrate the expression of functional p75 IL-2R on the patient's blast cells with NK cell properties.

Adolescent↗

Mutagenicity of N- and O-acetyl derivatives of methyl 3,4-diphenyl-5-hydroxylamino-2-furoate and N-hydroxy-4-aminobiphenyl in Salmonella typhimurium.

Methyl 3,4-diphenyl-5-hydroxylamino-2-furoate (N-OH-MDPF) (I), methyl 3,4-diphenyl-5-acetoxyamino-2-furoate (N-OAc-MDPF) (II), methyl 3,4-diphenyl-N-hydroxy-5-acetylamino-2-furoate (N-OH-MDPAF) (III), and methyl 3,4-diphenyl-N-acetoxy-5-acetylamino-2-furoate (N-OAc-MDPAF) (IV) were synthesized and tested for mutagenic activity for Salmonella typhimurium TA98 and TA100. The hydroxylamine (I) and acetyl derivatives (II-IV) did not show mutagenic activity in TA98 or TA100. In contrast, the parent nitro compound, methyl 3,4-diphenyl-5-nitro-2-furoate (MDPNF) (V) was found to be equally active in TA98 and TA98-DNP, and more active in TA100 and TA104. The mutagenic activity in TA100 and TA104 decreased significantly under anaerobic conditions. Additionally, MDPNF was previously shown to be less mutagenic in the nitroreductase-deficient derivatives TA100NR and TA98NR, suggesting a requirement for nitro reduction. Incubation of V with NADPH and bacterial lysates of TA98 or TA98NR yielded a metabolite which was identified as I based on chromatographic and mass spectral characteristics. The rate of reduction by the lysate of TA98NR was about one-third that of TA98, showing a correlation between mutagenicity and nitroreductase activity. The lysates of TA98 did not reduce N-OH-MDPF further to the amine. In contrast to the lack of mutagenic activity of I-IV, N-hydroxy-4-aminobiphenyl (N-OH-ABP) and its acetyl derivatives were active in TA98, but less so in TA98-DNP. These data suggest that mechanisms involving O-acetylation of N-hydroxylamine to the acetoxyamine or acyl transfer reactions are not involved in the generation of mutagen from MDPNF. Furthermore, the differential mutagenic response of V in TA98 and TA98NR, its reduction to I, and the lack of activity of I suggest that the intermediates of reduction between the nitro and hydroxylamine, such as nitro or nitroso free radical anions, may be involved in mutagenesis. The decreased response of V under anaerobic conditions and increased response in TA104 suggest that secondary oxygen radicals generated from reduction intermediates may be responsible for the mutagenicity of MDPNF.

Aminobiphenyl Compounds↗

A new multiple-unit oral floating dosage system. I: Preparation and in vitro evaluation of floating and sustained-release characteristics.

A multiple-unit type of oral floating dosage system, (a new type of floating pills which generate carbon dioxide gas) has been prepared in order to prolong the gastric emptying time (GET) of the preparation. The floating ability and the sustained-release characteristics of the system have been elucidated in vitro. The system was composed of sustained-release pills as seeds and double layers on the sustained-release pills. The inner layer was an effervescent layer containing both sodium bicarbonate and tartaric acid. The outer layer was a swellable membrane layer containing mainly polyvinyl acetate and purified shellac. When the system was immersed in water, it formed swollen pills, like balloons, with a density much lower than 1.0 g/mL. The reaction was due to carbon dioxide gas generated by neutralization in the effervescent layer with the diffusion of water through the swellable membrane layer. The system was floating completely within approximately 10 min and approximately 80% remained floating over a period of 5 h irrespective of pH and viscosity of the test medium. While the system was floating, a drug (p-aminobenzoic acid) was released. The release rate of the drug from the system was zero order and depended on the sustained-release characteristics of the sustained-release seeds composing the system. The release rate was not affected by the amount of the swellable membrane layer up to 13% (w/w).

Administration, Oral↗