Biomedical subjects

Y Kon

Publications and source records attributed to Y Kon.

At least 37 records · Page 2Linked to original sources

PubMed2000

[Efficacy of sustained-released theophylline on peak expiratory flow rate in asthmatic patients].

Nocturnal worsening is an important problem in asthma management. We evaluated the efficacy of two sustained-released theophylline formulations, administered twice-a-day (TD) and once-a-day (UP). In 20 asthmatic patients with low peak expiratory flow rate (PEF) in the morning (< 80% of predicted) administered TD (mean dose 475 mg/day) for 2 weeks, we evaluated PEF, diurnal variability of PEF, symptom score, results of spirometry and serum theophylline concentration (STC) and then changed theophylline, from TD to UP (mean dose 470 mg/day) for 2-4 weeks. PEF in the morning was higher during the UP period (mean +/- SD: 335 +/- 110 L/min) than during the TD period (mean +/- SD: 308 +/- 95 L/min) (p < 0.05), and diurnal variabirity of PEF was lower during the UP period (17.1 +/- 8.0%) than TD period (22.9 +/- 13.4%) (p < 0.05). However, there were no changes in PEF at night or daytime, symptom score, spirometry parameters or STC during the study period. The improvement in morning PEF observed in this study was consistent with the differences in pharmacokinetics between the two theophylline formulations. Morning PEF was increased during the UP period, probably because STC in the early morning during the UP period was higher than STC during the TD period.

Adult↗

PubMed2000

Embryonic hematopoiesis defect in the tattered-Hokkaido (Tdho) mouse.

BACKGROUND AND PURPOSE: The Tdho allele is an X-linked dominant, embryonic male-lethal mouse mutation that occurs between embryonic day (E) 12.5 and E14.5. The lethal cause and responsible gene have not been identified until now. The cause of lethality in Tdho male embryos was examined with respect to the defect of hematopoiesis. METHODS: Suppression subtractive hybridization and Northern blot analysis were performed on E12.5 male Tdho and normal mouse embryos. In addition, histochemical examinations and blood cell counts of normal and mutant E12.5 embryos were carried out. RESULTS: Diminished expression of embryonic globin genes (zeta and epsilon globins) in the blood of E12.5 Tdho male embryos were documented by use of Northern blot analysis and subtractive hybridization. Increased apoptosis of yolk sac-derived erythrocytes was found in E12.5 Tdho male embryos. Furthermore, diminished numbers of anucleated erythrocytes were observed in E12.5 mutant embryos. CONCLUSIONS: A defect of embryonic hematopoiesis in Tdho mice was suggested as one of the possible causes of embryo lethality.

Animals↗

PubMed1999

The role of Pseudomonas aeruginosa elastase as a potent inflammatory factor in a rat air pouch inflammation model.

Pseudomonas aeruginosa, an opportunistic pathogen, can cause life threatening infections in patients compromised by underlying respiratory disease like bronchiectasis, cystic fibrosis and diffuse panbronchiolitis. Most strains of P. aeruginosa produce some kind of protease with broad substrate specificities during the infectious state in the host. P. aeruginosa elastase, one of the strongest exotoxins, has a tissue-damaging proteolytic activity and is capable of degrading such plasma proteins as immunoglobulins, complement factor and cytokines. The present study focused on the effect of P. aeruginosa elastase and was designed to evaluate the neutrophil accumulation at the inflammation site mediated by P. aeruginosa elastase in the inflammatory response in the host. An air pouch model in rats, considered as a useful model of inflammation, was used to analyze the number of leukocytes, the volume of exudate and the concentration of interleukin-8 after the injection of P. aeruginosa elastase into the pouch cavity. The number of neutrophils and the volume of exudate in the pouch cavity increased significantly at 4 h, peaked at 8 h in a dose-dependent manner and then decreased at 24 h. The concentration of interleukin-8 in pouch fluid peaked 4 h earlier than the peak of the neutrophil number. The enzymatic activity of P. aeruginosa elastase seemed to reinforce the inflammation process. The influence of lipopolysaccharide contamination was negligible. Although these observations were made in the subcutaneous cavity, they indicate that P. aeruginosa elastase plays a role as an immunoprovocative factor in the inflammatory response in cases of infection with P. aeruginosa.

Air↗

PubMed1999

Expression of protein gene product 9.5, a neuronal ubiquitin C-terminal hydrolase, and its developing change in sertoli cells of mouse testis.

Protein gene product 9.5 (PGP9.5), originally isolated as a neuron-specific protein, belongs to a family of ubiquitin carboxyl-terminal hydrolases that play important roles in the nonlysosomal proteolytic pathway. Antibodies against PGP9.5 have been used for immunohistochemical detection of neural elements, although some non-neuronal cells are also immunoreactive for PGP9.5. In the present study, developing testes of the mouse were immunostained after autoclave pretreatment of sections. In the testes of days 8 and 16, PGP9.5 was only localized on the spermatogonia, whereas on day 30 and in adults it appeared not only on spermatogonia, but also on Sertoli cells. In the testis of the male sterile W/W(v) mutant, very little, but strong, immunoreactivity was detected at some Sertoli cells, which were phagocytizing Sertoli cell aggregations that had fallen from the basal membrane. Additionally, it was confirmed that the nucleotide sequence of PGP9.5 in mice was highly conserved, like that in other mammals. These results suggest that PGP9.5 is a useful marker for activated Sertoli cells, playing an important role in degradation of abnormal proteins.

Animals↗

PubMed1999

A Japanese herbal medicine, Chujo-to, has a beneficial effect on osteoporosis in rats.

The inhibitory effects of a Japanese herbal medicine, Chujo-to, on the progress of bone loss induced by ovariectomy in rats were investigated. Ovariectomized rats were administered with Chujo-to during weeks 7-14 after ovariectomy. At 14 weeks, the bone mineral density of the tibia from ovariectomized (OVX) rats had decreased by 27% compared with those in the sham-operated rats, and by a 18%-21% and 16% decrease after the administration of Chujo-to and 17 beta-oestradiol, respectively. The surface of a trabecular bone of the tibia in ovariectomized rats had a porous and fibrous appearance, while that of the same bone in sham-operated rats was composed of fine particles. After the administration of Chujo-to or 17 beta-oestradiol, the surface of trabecular bone maintained the porous and fibrous appearance. The uterine weight was not restored by Chujo-to but by 17 beta-oestradiol. These results suggest that Chujo-to has an efficacy on the osteoporosis of rats similar to 17 beta-oestradiol, but with a different mechanism.

Animals↗

PubMed1999

Jumbled spine and ribs (Jsr): a new mutation on mouse chromosome 5.

Jumbled spine and ribs (Jsr) is an autosomal dominant mutation that results in malformation of the axial skeleton. The vertebrae of mutant mice (Jsr/+) are all shorter than those of normal mice (+/+) in the inbred line and show various abnormalities. In addition, several ribs are fused at their proximal region because of fusion of thoracic vertebrae. In this study, we localized the Jsr mutation on distal Chromosome (Chr) 5 and constructed a high-resolution map. Chromosomal mapping was performed with an inter-subspecific backcross of (CKH-Jsr/+ x MOG) F1 carrying the Jsr allele and CKH-+/+. The predicted gene order around Jsr was determined to be cen-(Epo, Pdgfa, D5Mit31, D5Mit374)-(Jsr, Nfe2u, D5Mit99, D5Mit247, D5Mit284, D5Mit292, D5Mit327)-D5Mit328-tel. Subsequently, high-resolution mapping concluded the Jsr localization to be cen-Nfe2u-1.0cM-Jsr-0.2cM-D5Mit247,292-tel . Jsr/Jsr homozygotes are alive, as the mutation is not lethal. Based on histological analysis of mutant embryos, Jsr is hypothesized to be caused by abnormal development of primordial cells in the axial skeleton.

Animals↗

PubMed1999

Metaphase-specific cell death in meiotic spermatocytes in mice.

Apoptosis of male germ cells is a widespread but little-understood phenomenon in many animal species. The elucidation of its mechanisms could be useful in the understanding of male infertility. We have examined the distribution of dying cells with the terminal transferase-mediated nick-end labeling (TUNEL) method and by an electron-microscopic procedure in the testes of 10 mouse strains, viz., C57BL/10 (B10), SL/NiA (SL), C57BL/6 (B6), C3H/He (C3H), BALB/c (BALB), DBA2 (DBA), CBA/J (CBA), MRL/MpJ(-)+/+ (M+), MRL/MpJ-lpr/lpr (lpr), and wild-type NJL mice (Mus musculus musculus). In the testes of the B10, NJL, SL, B6, C3H, BALB, DBA, and CBA mice, very few TUNEL-positive cells are distributed in the seminiferous tubules, whereas in the testes of the M+ and lpr mice, many TUNEL-positive cells, which are restricted to stage XII seminiferous tubules, have been identified. The most important finding is that many metaphases of meiotic spermatocytes show a marked TUNEL-positive reaction. Some metaphases show apoptotic morphology electron-microscopically. These results suggest that the testes of MRL strains will provide a useful model for the study of the mechanism of metaphase-specific apoptosis in meiotic spermatocytes.

Animals↗

PubMed1999

Expression of angiotensinogen in the uterus induced by coagulating gland renin in mice.

Coagulating gland (CG) renin is one of the components of the local renin-angiotensin system (RAS), which plays important roles in the maintenance of homeostasis in several tissues. Although the existence of local renin has been reported in many tissues, its function is not yet well understood. In the present study, the relationship between CG renin and uterine angiotensinogen was investigated by immunohistochemical and in situ hybridization techniques. In mating experiments with male and female C57BL/6 mice, renin was demonstrated immunohistochemically on the epithelial cells of the uterus on the first day after coitus; however, it was not detected on the second and third days after coitus. Neither immunoreactive cells nor messenger signals for renin were demonstrated on the epithelial cells of the uterus throughout the experiments. On the first day after mating, it was noted that positive signals for angiotensinogen mRNA were expressed on the epithelial cells of the uterus in situ hybridization, but not on the second and third days after coitus. These results suggest the possibility that CG renin is transferred to the uterine epithelium at mating and temporarily activates the expression of angiotensinogen in the uterus. Angiotensin II produced by angiotensinogen may act as an important mediator for vascularization of the first step of pregnancy.

Angiotensinogen↗

PubMed1999

Renin in exocrine glands of different mouse strains.

The renin-angiotensin system (RAS) controls the regulation of blood pressure and water-mineral balance. Recently, renin has been reported to be synthesized and secreted outside the kidney. The present study investigated immunohistochemically the distribution of renin in exocrine glands, i.e. salivary glands and coagulating glands, in male mice of 13 strains. In some strains, renin was detected in the sublingual and submandibular salivary glands, but not in the parotid glands. It was restricted to the striated or granular portions of excretory ducts. In coagulating glands, variable staining patterns were found. These results demonstrate the existence of variations in renin content in mouse strains and offered a selection of mouse strains for investigation of exocrine gland renin.

Animals↗

PubMed1999

Identification of the murine Mx2 gene: interferon-induced expression of the Mx2 protein from the feral mouse gene confers resistance to vesicular stomatitis virus.

The mouse genome contains two related interferon-regulated genes, Mx1 and Mx2. Whereas Mx1 codes for the nuclear 72-kDa protein that interferes with influenza virus replication after interferon treatment, the Mx2 gene is nonfunctional in all laboratory mouse strains examined, since its open reading frame (ORF) is interrupted by an insertional mutation and a subsequent frameshift mutation. In the present study, we demonstrate that Mx2 mRNA of cells from feral mouse strains NJL (Mus musculus musculus) and SPR (Mus spretus) differs from that of the laboratory mouse strains tested. The Mx2 mRNA of the feral strains contains a single long ORF consisting of 656 amino acids. We further show that Mx2 protein in the feral strains is expressed upon interferon treatment and localizes to the cytoplasm much like the rat Mx2 protein, which inhibits vesicular stomatitis virus replication. Furthermore, transfected 3T3 cell lines of laboratory mouse origin expressing Mx2 from feral strains acquire slight resistance to vesicular stomatitis virus.

Amino Acid Sequence↗

PubMed1999

Comparative study of renin-containing cells. Histological approaches.

The juxtaglomerular apparatus is known to be the functional unit of renin control. In the present review, the author will describe the comparative characteristics of renin-containing (RC) cells as well as extrarenal distribution, paying special attention to developmental and topographical approaches. The characteristic locality of RC cells suggests that the secretion of renin is performed at a site beside the adventitia or via the glomerular capillaries. Ontogenetical and phylogenetical investigations of RC cells have provided interesting findings on their morphogenesis. Analysis of the endocrine kidney after unilateral obstruction of the ureter provides some findings about the origin of RC cells and the processing of renin granules. Observation of developing adrenal renin suggests that there is important involvement of angiotensin II produced by renin synthesis in the morphogenesis of the adrenal gland in the fetal stage. Coagulating gland (CG) renin is characterized by testosterone-regulated and exocrine mechanisms. Recently, all or some of the components of the renin-angiotensin system (RAS) have been reported to be synthesized and secreted outside of classical organs or tissues. In the future, the real function of local RAS will be clarified by using gene targeting in mice.

Adrenal Glands↗

PubMed1999

MR imaging of hepatic injury in the LEC rat under a high magnetic field (7.05 T).

Visualization of copper-induced hepatitis (CuH) in LEC rats was performed by using an MRI apparatus equipped with a magnet producing a high magnetic field of 7.05 T. When three groups of LEC rats (6-16 [pre-hepatitis], 15-26 [acute hepatitis] and 40-77 [chronic hepatitis] weeks old) were examined by MRI under T2-weighted imaging conditions which are suitable for the diagnosis of human hepatitis, hypointense MR images of the livers were, as a whole, obtained in all groups, suggesting that these conditions were not adequate for imaging of CuH of LEC rats. The shortening of the T1 and T2 relaxation times of livers due to an excess amount of paramagnetic irons under the high magnetic field was responsible for the lowering of MR signal intensities of the livers, especially those of 15 to 26-week old rats showing acute hepatitis. However, theoretical calculation of the MR signal intensities using the T1 and T2 relaxation times of the livers indicated that their imaging might be possible under proton density-weighted conditions even with a high magnetic field. Experimental results showed that hepatic injury was visualized as hyperintense regions in the MR image of the liver in the acute-phase rat.

Animals↗

PubMed1999

Expression and characterization of mouse angiotensin II type 1a receptor tagging hemagglutinin epitope in cultured cells.

The octapeptide angiotensin II mediates the physiological actions of the renin-angiotensin system through activation of several angiotensin II receptor (AT) subtypes, in particular AT1 (AT1a and AT1b in the case of rodents). Although we and others have generated mutant mice in which the AT1a gene was disrupted, the function of mouse AT1 remains to be fully elucidated, due to the lack of effective tools involving antibodies against AT1 for detecting biological responses in cellular conditions. To avoid these problems, we constructed the hemagglutinin (HA)-tagged mouse AT1a, and stably introduced this recombinant receptor into human embryonic kidney 293-T cells. Radioligand binding of [(125)I] angiotensin II to AT1a was specific, saturable, and reversible. Scatchard analysis demonstrated that the transfected receptor had a dissociation constant of 1.7 nM with a density of 1.2 x 10(5) sites/cells. Angiotensin II stimulated a rapid increase in cytosolic free calcium, and angiotensin II-induced phosphorylation of extracellular signal-regulated kinases (Erk) was found in a dose-dependent manner. After solubilization, Western blot analysis showed specific interactions between an anti-HA antibody and HA-tagged mouse AT1a. Furthermore, a significant proportion of HA-tagged mouse AT1a was specifically immunoprecipitated with this antibody. In the immunocytochemical and electronmicroscopic studies, treatment of this cell line with angiotensin II resulted in decrease in signals of the surface receptors. Based on these results, the cell line established here provides an excellent tool for studying angiotensin II actions mediated through mouse AT1a, at sub-nanomolar concentrations.

Angiotensin II↗

PubMed1999

[Medical therapy in ulcerative colitis].

Salazosulfapyridine(SASP) and 5-aminosalicyclic acid(5-ASA) are useful in the therapy of mildly to moderately active ulcerative colitis. 5-ASA lacks sulfa moiety of SASP and is associated with a decreased incidence of side effects. In patients with moderate or severe ulcerative colitis, glucocorticoids which may be given in conjunction with SASP or 5-ASA are beneficial in producing remission. Proctitis or left-sided colitis is effectively treated with glucocorticoid enemas. If symptoms are refractory to outpatient management, the patient should be hospitalized and given initial therapy with glucocorticoids. Total colectomy(ileo-anal anastomosis; IAA et al) must be considered for acutely ill patients not responding to intensive medical therapy. Early surgical consultation is necessary in severely ill patients.

Anti-Inflammatory Agents↗

PubMed1999

Effects of concurrent exposure to 3-methylcholanthrene and vitamin A on fetal development in rats.

To investigate the effect of the environmental pollutants, polycyclic aromatic hydrocarbons (PAHs), on retinoic acid-induced teratogenesis, all-trans-retinoic acid (RA) dissolved in corn oil (120 mg/kg) was administered orally to pregnant rats at the 11th day of gestation with and without the prior intraperitoneal treatment with 10 mg/kg 3-methylcholanthrene (3-MC) for 3 days. Dams were killed on the 20th day of pregnancy. The examinations of fetuses revealed that 3-MC barely enough to cause induction of P-450 in pregnant dams had profound embryo-toxic effects: the fetal resorption amounted to approximately 60% of total number of implantations. The fetuses survived weighed less than the control fetuses. All of RA-treated mothers had fetuses with abnormalities, and the main malformations were absence of tail (100%), caudal and sacral malformations (100%), and cleft palate (42%). Pregnant dams received both 3-MC and RA had a reduced severity of tail anomaly (33%), while the rest, 67%, had short vestigial tail. Caudal and sacral malformations were detected but at a milder degree. We did not observe cleft palate in this group. The concurrent treatment of dams with 3-MC and RA led to an increased inducibility of cytochrome P-450 and subsequently, CYP1A1 dependent enzyme activity higher than those observed after the injection of 3-MC alone. UDP-glucuronyl-transferase activity was also markedly induced in concurrent 3-MC and RA group higher than that in 3-MC alone. We suggest that the induction of P-450 and alteration of metabolic enzyme activities may play an important role in reducing the teratogenic potency of RA. However, RA-treatment did not retard the embryo-toxic effect of 3-MC but rather potentiated.

Abnormalities, Drug-Induced↗

PubMed1998

Intramuscular injection of plasmid DNA expressing mRNA7 coding the nucleocapsid protein of JHMV partially protected mice against acute infection with JHMV.

We constructed a plasmid expressing mRNA7 coding the nucleocapsid (N) protein of JHM strain of mouse hepatitis virus (JHMV) under the control of Rous sarcoma virus LTR, referred to as pRSV-mRNA7. When C57BL/6 mice injected intramuscularly (i.m.) with control plasmid DNA which contained no viral sequence were infected with JHMV, necrotic figures of neural cells and diffuse immersion of lymphatic cells in the pedunculus cerebri were observed. In the hypothalamus, vascular cuffing consisting of lymphatic cells was observed. In contrast, no histological change was observed throughout these areas of the brains in the JHMV-infected mice after injection with pRSV-mRNA7. These results showed that the injection with plasmid DNA expressing mRNA7 of JHMV partially protected mice against acute infection with JHMV in the brain. The plasmid DNA was i.m. injected into mice and the cytolytic activity of spleen cells from the mice was assessed by 51Cr-release assay. The spleen cells from the mice administrated with pRSV-mRNA7 showed a significant level of cytolytic activities against the transfected cells expressing the viral N protein even though the spleen cells were not cocultivated with stimulator cells. When the spleen cells from administrated mice with pRSV-mRNA7 were cocultivated with stimulator cells, higher cytolytic activity was observed against the transfected cells, compared with the activity without stimulation.

Acute Disease↗

PubMed1998

Expression of renin in the rat liver.

Renin is well-known to be a trigger enzyme in the renin-angiotensin system (RAS). In contrast to the classical RAS, the local RAS has recently been noted in several tissues. The local RAS has a function independent from that of the classical RAS, although its physiological principles are not well known. In the present study, we immunohistochemically demonstrated that hepatocytes in the rat express renin. No renin-immunoreactive cells were detected in rat liver at 0 min after death. At 15 min after death, a small number of renin-positive cells was demonstrated in the lamina hepatica, and they increased with time to the end of observation. Immunoreactivity for renin was scarce throughout the cytoplasm, sometimes condensed to below the cell membrane and around the intracellular granules. Histoplanimetrically, the values from 15 min to 120 min after death were significantly different from that at 0 min after death. Hybridohistochemistry revealed no hybrid signals throughout the liver at either 0 min or 30 min, although renin-immunoreactivity was clearly demonstrated in adjacent sections of liver at 30 min after death. In RT-PCR, the radioactivities in kidney and liver at 0 min after death were not different from those at 30 min after death, respectively. These results suggest the existence of hepatic renin in the rat.

Animals↗

PubMed1998

Chemoreceptive epithelioid cells in the chicken aorta. An electron microscopical study.

Aggregations of granulated epithelioid cells exist in the chicken aorta. In the present study, the locational characteristics of the epithelioid cells were investigated via an electron microscopic approach. Epithelioid cells were found mainly in two regions; the tunica interna just below the endothelial cell layers, and the intermediate region of the tunica media. In the former, the epithelioid cells were in contact with endothelial cells and sometimes directly exposed to the aortic lumen. No contact between the epithelioid cells and the nerve endings was observed in this region. On the other hand, in the intermediate region of the tunica media, five or more epithelioid cells were aggregated, and the synaptic structures were occasionally observed. Additionally, the epithelioid cells in this region was observed to closely contact smooth muscle cells. In an experiment using horseradish peroxidase injection, reactions were detected in the intercellular spaces between the epithelioid cells and endothelial cells. These results suggest that the epithelioid cells localized in the subendothelial region receive information from the aortic lumen, whereas their aggregations in the tunica media are controlled by the nervous system.

Animals↗