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Biomedical subjects

T Iwanaga

Publications and source records attributed to T Iwanaga.

At least 37 records · Page 2Linked to original sources

Germinated barley foodstuff feeding. A novel neutraceutical therapeutic strategy for ulcerative colitis.

A germinated barley foodstuff (GBF) contained glutamine-rich protein and the hemicellulose-rich fiber was made from brewer's spent grain by physical isolation (milling and sieving). Both in vivo and in vitro studies demonstrated that the fiber fraction of GBF supports maintenance of epithelial cell populations, facilitates epithelial repair, and suppresses epithelial nuclear factor kappa B-DNA binding activity through generating increased short-chain fatty acid (especially butyrate) production by luminal microflora which includes Bifidobacterium and Eubacterium, thereby preventing experimental colonic injury. The fiber fraction also modulates stool water content by its high water-holding capacity. The protein fraction which contains larger glutamine prevents experimental small bowel injury. Based on these observations, clinical studies were initiated in patients with mild to moderate active ulcerative colitis. The patients who had been unresponsive to or intolerant of standard treatment received 30 grams of GBF feeding daily in a nonrandomized, open-label fashion. At 4 weeks, this treatment resulted in a significant clinical and endoscopic improvement independent of disease extent. The improvement was associated with an increase in stool butyrate concentrations and in luminal Bifidobacterium and Eubacterium levels. After the end of GBF treatment the patients had an exacerbation of the disease. GBF was safe and well tolerated. These results indicate that GBF feeding is a potentially attractive treatment in patients with ulcerative colitis.

Administration, Oral↗

Ivermectin treatment of demodicosis in 56 hamsters.

Fifty-six hamsters with demodicosis were treated with daily oral administration of ivermectin (0.3 mg/kg). Thirty-three cases (58.9%) were cured and 6 cases (10.7%) had improved clinically but needed to continue treatment. Of 5 cases (8.9%) who relapsed within 3 months and were retreated with ivermectin, 4 were cured and 1 needed further treatment. Five cases (8.9%) had improved clinically but died within 3 months. Seven cases (12.5%) had not improved and died within 3 months. Overall 49 (87.5%) hamsters had improved clinically. No significant differences in prognosis of demodicosis were detected according to sex, breed, age and clinical features, but the prognosis of demodicosis in hamsters with concurrent disease was poor.

Animals↗

Hydrocephalus and syringomyelia in a cat.

A 3-month-old male Japanese cat with feline parvovirus infection, showing central and cervical nerve abnormalities, was diagnosed as hydrocephalus and syringomyelia by use of magnetic resonance imaging (MRI). The cat was maintained clinically by medical treatment even though he could not stand. The MRI scans obtained about 5 months later showed that the ventricles had increased in size and the cervical syrinx had extended into the thoracic spinal cord. Ventriculoperitoneal (VP) shunt was performed. One week after surgery, neurological conditions had improved. At the postoperative MR images, the ventricles had decreased in size and the syrinx in the cervical and thoracic spinal cord could no longer be seen. The cat was still alive and was able to walk well.

Animals↗

Expression of estrogen receptor-alpha and -beta mRNAs in the male reproductive system of the rat as revealed by in situ hybridization.

We mapped the cellular expression of estrogen receptor (ER) alpha and ERbeta mRNAs in the male reproductive system of the rat during development and adulthood by in situ hybridization. The expression patterns of ERalpha mRNA in the gonad, efferent duct and initial segment of the epididymis during the perinatal period were essentially similar to those of the adult: ERalpha mRNA signals were expressed most intensely in the epithelia of the efferent ducts and initial segment of the epididymis, and in the interstitial cells of the testis from the prenatal period to adulthood. However, ERalpha mRNA signals in the primordial epididymis and vas deferens during the prenatal period were confined to the outermost cellular layer of the ducts, whereas thereafter they were only expressed weakly in the epithelium and stroma of the epididymis and moderately in the muscle layer of the vas deferens. ERbeta signals were expressed intensely (1) in primordial germ and Sertoli cells only during the prenatal period, (2) in arterial walls in the adult testis, and (3) in the epithelium of the sex accessory glands from the perinatal period to adulthood. This report is the first to describe the cellular distribution of ER mRNA in the male reproductive organs during the perinatal period, and complements and confirms earlier data on its distribution in the adult. The broad expression of ERs in male reproductive organs suggests roles for estrogen in regulating tissue development and reproductive events.

Animals↗

Cellular distribution of napsin (kidney-derived aspartic protease-like protein, KAP) mRNA in the kidney, lung and lymphatic organs of adult and developing mice.

Kidney-derived aspartic protease-like protein (KAP), initially identified in the mouse kidney, is a novel aspartic protease exclusively expressed in the lung and spleen as well as the kidney. Its orthologues have been identified in the human and rat, and termed napsin. We performed in situ hybridization analysis to determine the cellular expression of napsin mRNA in the kidney, lung, and lymphatic organs of adult mice and to demonstrate, for the first time, its expression patterns in ontogeny. In the adult mouse kidney, extremely intense signals for napsin mRNA were observed in the proximal straight and convoluted tubules, in agreement with a previous study. The first signals for napsin mRNA during nephrogenesis occurred selectively in mesonephric tubules at embryonic day 13, and in metanephric tubules from embryonic day 14. In the lung, a distribution restricted to type II alveolar cells or their precursors was found from embryonic day 15, at the onset of type II cell differentiation, to the adult stage. In the spleen, the mRNA was expressed in lymph nodules of the white pulp and the marginal zone-namely, B-lymphocyte-rich regions from postnatal day 0 to adult. The lymph node and Peyer's patch displayed similar expression patterns, but T cell-dependent areas in these organs and the thymus lacked such signals. These findings suggest that mouse napsin possesses crucial functional roles not only in the kidney but also in the lung and lymphatic tissues, even during fetal stages.

Animals↗

Cellular localization of the diazepam binding inhibitor (DBI) in the gastrointestinal tract of mice and its coexistence with the fatty acid binding protein (FABP).

The diazepam binding inhibitor (DBI), initially isolated as an endogenous 10-kDa polypeptide from the brain, has the ability to displace ligands from benzodiazepine binding sites on gamma-aminobutyric acid (GABA) receptors. However, DBI is widely distributed outside the brain, with the highest expression in the intestine. The present in situ hybridization study revealed the cellular expression of DBI mRNA throughout the gastrointestinal tract of mice, showing it to be intensely expressed in the spinous layer in the stratified squamous epithelium of the oral cavity, esophagus and forestomach, in surface mucous cells in the glandular stomach, and in columnar (absorptive) cells of the intestinal villi. A precise identification of DBI-expressing cell types was confirmed immunohistochemically, although the expressing cells detectable by the two histochemical methods differed slightly in their extension. Noteworthily, DBI always coexisted with the fatty acid binding protein (FABP), which participates in the uptake and metabolic processing of long chain fatty acids. In addition to the biochemical finding that DBI is identical with the acyl-CoA binding protein (ACBP), the distributional patterns of DBI and its colocalization with FABPs suggests its involvement in the absorption and metabolism of lipid in the epithelia of the digestive tract.

Animals↗

Morphological changes in pancreatic islets of KATP channel-deficient mice: the involvement of KATP channels in the survival of insulin cells and the maintenance of islet architecture.

The ATP-sensitive potassium channel (KATP channel) is an essential ion channel involved in glucose-induced insulin secretion. The KATP channel is composed of an inwardly rectifying potassium channel, Kir6.2, and the sulfonylurea receptor (SUR 1); in the pancreas it is reported to be shared by all endocrine cell types. A previous study by our research group showed that Kir 6.2-knockout mice lacked KATP channel activities and failed to secrete insulin in response to glucose, but displayed normal blood glucose levels and only mild impairment in glucose tolerance at younger ages. In some aged knockout mice, however, obesity and hyperglycemia were recognizable. The present study aimed to reveal morphological changes in pancreatic islets of Kir 6.2-knockout mice throughout life. At birth, there were no significant differences in the islet cell arrangement between the knockout mice and controls. At 14 postnatal weeks glucagon cells appeared in the central parts of islets, and this image became more pronounced with aging. In animals older than 50 weeks insulin cells decreased in numbers and intensity of insulin immunoreactivity; most islets in 70- and 80-week-old mice were predominantly composed of glucagon cells and peptide YY (PYY)-containing cells. Staining of serial sections and double staining of single sections from these old mice demonstrated the frequent coexpression of glucagon and PYY, which is a phenotype for the earliest progenitor cells of pancreatic endocrine cells. These findings suggest that the KATP channel is important for insulin cell survival and also regulates the differentiation of islet cells.

Adenosine Triphosphate↗

Acute interstitial pneumonia induced by ONO-1078 (pranlukast), a leukotriene receptor antagonist.

A 62-year-old woman treated with pranlukast for 2 months developed interstitial pneumonitis with a high fever. A lymphocyte stimulation test was reactive to pranlukast. Her clinical symptoms improved with discontinuation of pranlukast and administration of systemic corticosteroid. To our knowledge, this is the first reported case of drug-induced lung disease involving a leukotriene. The steps that can be taken to promptly reach a diagnosis and to successfully treat this life-threatening condition are described.

Acute Disease↗

Roles of ATP-sensitive K+ channels in cell survival and differentiation in the endocrine pancreas.

To determine the roles of the ATP-sensitive K+ (K(ATP)) channels in endocrine pancreas more directly, two types of genetically engineered Kir6.2 mice were developed: mice expressing a dominant-negative form of Kir6.2 specifically in beta-cells (Kir6.2G132S Tg mice) and mice lacking Kir6.2 (Kir6.2-/- or Kir6.2 null mice). The Kir6.2G132S Tg mice show severe impairment of K(ATP) channel function only in the beta-cells, whereas Kir6.2 null mice are completely defective in K(ATP) channel function in all of the cells in which Kir6.2 is a constituent of the K(ATP) channels, because of the disruption of Kir6.2. Both types of mice show abnormal architecture of the pancreatic islets. The number of beta-cells in Kir6.2G132S Tg mice decreases markedly with age, whereas that in Kir6.2-/- mice decreases slightly. alpha-Cells, which are normally present only in the periphery of pancreatic islets, also appear in the center of the islets in both Kir6.2G132S Tg and Kir6.2-/- mice. Interestingly, the number of peptide YY (PYY) and glucagon-positive cells is markedly increased in Kir6.2 null mice, whereas the number of PP cells and delta-cells is not altered. Apoptotic cells are detected by the TdT-mediated dUTP nick-end labeling (TUNEL) method at a high frequency in both Kir6.2G372S Tg and Kir6.2-/- mice compared with the respective controls. Thus, studies of Kir6.2G372S Tg and Kir6.2-/- mice indicate that K(ATP) channels play an important role in cell survival and differentiation in the endocrine pancreas.

Adenosine Triphosphate↗

[Long-term study of airborne allergic pollen count, C. Japonica and cupressaceae in Japan].

We have investigated the distribution of airborne pollen at the different eleven points in Japan from 1987 to 1998 using gravity sampler. To clarify the characteristics causative pollen for Japanese cedar pollinosis, we examined annual change of pollen counts, dispersing period and geographical difference of C. japonica and Cupressaceae pollen. C. japonica pollen occupied much more in Central Japan and Cupressaceae in the west of Japan than the other area. In Hamamatsu City, both of pollen counts were most of all and we found a tendency that the more pollen counts the longer dispersing period. As they reported that at the starting day of pollen in this method some patients had already suffered from allergic symptoms, we considered pollen grains were dispersing in spite of being continuously captured. In these twelve years we found that patients with Japanese pollinosis are exposured by causative agents during about 100 days every spring. But we could not observe the trend of increasing pollen counts and earlier starting day because of global warming. Further more we found that the pollen counts of C. japonica in autumn was increasing since 1994. As one of the factors of increasing patients with pollinosis, we thought that total exposure period of causative pollen every year were longer than that of 1980s.

Air Pollutants↗

[Clinical study on the cases in which INH or RFP was discontinued during treatment for pulmonary tuberculosis].

Short course regimens; 2HRZ (E)(S)/4HR (E), 6HRS (E)/3-6HR and 6-9HR have been accepted as a standard chemotherapy (SC) for initial treatment of pulmonary tuberculosis in Japan. We studied the frequency of the treatment completion, the causes of the treatment failure and the outcome of the patients in whom INH or RFP was discontinued within 6 months after starting SC. The subjects included 597 newly diagnosed culture positive pulmonary tuberculosis patients admitted to 16 national hospital in 1996. Results were as follows. 1. In 47 (7.9%) of the 597 patients, either INH (19; 3.2%) or RFP (33; 5.5%) was discontinued. These 47 cases were defined as a SC incompleted group and the other 550 as a SC completed group. 2. The patients in the SC incompleted group were seen more frequently in the ages of 20s (11.9%), 50s (10.9%), 60s (11.7%) or 70s (11.4%). 21 (13.6%) of 154 female patients and 26 (5.9%) of 443 male patients were in the SC incompleted group. 3. The causes of cessation of INH or RFP were drug side effects (33; 5.5%), drug resistance (10; 1.7%) and complications or underlying diseases (8; 1.3%). 4. Fever or eruption (19; 3.2%) and drug induced hepatitis (12; 2.0%) were frequently seen as drug related side effects causing the cessation of INH or RFP. 5. The rate of culture negative conversion of TB bacilli at 6 months after the start of the treatment was 98.9% in the SC completed and 88.9% in the SC incompleted group respectively. In the SC incompleted group, there were three cases continuously positive and two other patients who relapsed and became culture positive again. In these five patients, INH or RFP was discontinued because of drug resistance.

Adolescent↗

Immunohistochemical demonstration of chromogranin A in endocrine organs of the rat and horse by use of region-specific antibodies.

Chromogranin A (CgA) is an acidic glycoprotein that is co-stored with hormones or neurotransmitters in granular components of endocrine cells and neurons, and released together with them in response to adequate stimulation. In addition to acting as a packaging protein, CgA functions as a precursor molecule that yields several bioactive peptides by proteolytic cleavage. The purpose of this study is to elucidate how different the processing of CgA is among endocrine tissues by immunostaining using multiple region-specific antisera, and to evaluate the availability of region-specific antisera. When various endocrine organs of rats were immunostained with four region-specific antisera against rat CgA (CgA 1-28, 94-130, 296-314, and 359-389), all amine/peptide-secreting endocrine tissues except the pineal body were stained positively. The adrenal medulla and gastric endocrine cells were equally intensely immunoreactive to all four antisera, while the other endocrine tissues, represented by pancreatic islets, showed different staining patterns depending on the antiserum. These results suggest that the processing of CgA differs from tissue to tissue. An antiserum against horse CgA 335-365, corresponding to rat CgA 359-389 which shows the highest concentration in the plasma and urine of the rat, again stained all endocrine tissues of the horse except the pineal body. Therefore, the anti-horse CgA 335-365 serum is useful for immunohistochemical survey of horse CgA, and may make possible the establishment of a CgA assay system for the measurement of CgA in the plasma, urine and saliva.

Animals↗

Increased concentrations of protein gene product 9.5 in the synovial fluid from horses with osteoarthritis.

Our previous study established protein gene product 9.5 (PGP 9.5), a ubiquitin C-terminal hydrolase, as a specific cytochemical marker of synovial lining cells (type B synoviocytes) in the horse joint. The present study aimed to detect PGP 9.5 in the synovial fluid and shows that PGP 9.5 is a valuable marker of osteoarthritis in the horse. Immunohistochemical staining confirmed rich and consistent localization of PGP 9.5 immunoreactivity in the cytoplasm of synovial lining cells in the normal horse joint. Western blot analysis of synovial fluid from normal joints could detect a significant band corresponding to that contained in the brain and synovial membrane extracts. When 60 synovial fluid samples from normal and abnormal joints were assayed with an enzyme-linked immunosorbent assay (ELISA) system, the concentration of PGP 9.5 tended to be elevated in osteochondrosis dissecance, inflammatory arthropathy and intra-articular fracture, among which a statistically significant elevation was recognizable between the intra-articular fracture and the control. Thus, this study demonstrated the possibility that PGP 9.5, derived from synovial lining cells, may be a new biochemical marker for arthritic disorders of the horse.

Animals↗

[The impact of obesity on oxygen desaturation in patients with sleep apnea/hypopnea syndrome].

We performed a cross-sectional investigation on the impact of obesity on clinical manifestations in patients with obstructive sleep apnea/hypopnea syndrome (SAHS). The subjects were 87 patients who underwent overnight polysomnography with an apnea/hypopnea index (AHI) of 15/h or more. We divided these patients into non-obese (N) and obese (O) groups based on the median value of the body mass index (BMI), 27 kg/m2. Subjective symptoms, sleep quality and AHI were similar in both groups, but every parameter related to oxygen desaturation was worse in group O than in group N. There was no difference in the mean duration of apnea events between the two groups. The rate of fall in oxygen saturation during apnea events was highly correlated to the BMI (r = 0.72; p < 0.00001). Accordingly, we concluded that profound desaturation in group O is due to a rapid fall in oxygen saturation during apnea events compared with group N. Anthropometric measurements revealed that the rate of fall in oxygen saturation was more related to abdominal circumference (AC) than the neck circumference (NC), which is contrasted with the finding that AHI was more related to NC than AC. This fact suggests that abdominal obesity may deteriorate oxygenation during apnea events and may therefore aggravate the risk of cardiovascular disease in patients with SAHS.

Adult↗

[A case of acute disseminated encephalomyelitis after renal transplantation].

We report a patient of acute disseminated encephalomyelitis (ADEM) in a recipient of renal transplantation. A 43-year-old man suffered from generalized convulsion and consciousness disturbance followed by coma on day 53 of after the transplantation. He was receiving several immunosuppressants, and an increase of serum antigen for cytomegalovirus was observed one day before the ictus. T2 and diffusion-weighted image of MRI showed high intensity lesions in the bilateral cerebral white matter, basal ganglia, thalamus, midbrain, pons and cerebellum. Examination of cerebrospinal fluid revealed elevated myelin basic protein level. The patient was diagnosed as having ADEM and was treated with methylpredonisolone pulse therapy in combination with intravenous immune globulin. He gradually recovered and became capable to eat and sit on a wheel chair. White matter lesions on MRI were also diminished. ADEM may occur in recipients of organ transplantation even if they have immunosuppressive treatment.

Acute Disease↗

Regulation of the successive reaction catalyzed by rat neuronal nitric oxide synthase.

The rat neuronal nitric oxide synthase (nNOS) catalyzes two monooxygenase reactions successively from L-arginine (L-Arg) to L-citrulline (L-Cit) via N(omega)-hydroxy-L-arginine (OH-Arg) without most of OH-Arg leaving the substrate-binding site. In the steady-state reaction conditions, the amount of OH-Arg produced is about 1/30-1/50 that of L-Cit. We found in this study using nNOS purified from an Escherichia coli expression system that the ratio of the amount of OH-Arg to L-Cit (OH-Arg/L-Cit) increased to about 1 at low concentration of NADPH. In one cycle of the nNOS reaction, the decrease in NADPH concentration was found to reduce the rates of two monooxygenase reactions but had little effect on the rate constant of OH-Arg dissociation from the enzyme. The addition of NADP(+), the competitive inhibitor for NADPH, caused the decrease in the rates of monooxygenase reactions in a single cycle of the reaction and the increase in the ratio of OH-Arg/L-Cit in the steady state. At low CaM concentrations, the ratio of OH-Arg/L-Cit was about the same as that at high CaM. In a single cycle of the nNOS reaction, the rate of monooxygenation was not altered by the CaM concentration but the amount of metabolized L-Arg decreased with the decrease in CaM concentration, showing that the amount of active nNOS was regulated by complex formation between nNOS and CaM. It becomes clear that there are two regulatory mechanisms for the successive reaction of nNOS. One controls the rates of monooxygenations and the other controls the amount of active species of nNOS.

Animals↗

Characterization of p-chloroamphetamine-induced penile erection and ejaculation in anesthetized rats.

Methodological shortcomings present in elicitation of male sexual reflexes in anesthetized animals. The present study has demonstrated, however, that intraperitoneal (i.p.) injection of p-chloroamphetamine (PCA), an indirect serotonin (5-HT) agonist, elicited simultaneously both penile erection and ejaculation in anesthetized rats. PCA (2.5-10.0 mg/kg, i.p.) caused an intermittent cluster of genital responses consisting of penile erection, glans erections, and penile cups, which closely resembles the response observed during the ex copula tests in unanesthetized rats. Measurements of intracavernous penile pressure showed that rhythmic changes in penile pressure were produced by PCA, together with glans erections and penile cups. PCA also caused a frequent ejaculations and the weighing of ejaculate accumulated over 0.5 hr was increased in a bell-shaped pattern, and the maximum effect was observed at 5.0 mg/kg. Pretreatment with p-chlorophenylalanine, a serotonin (5-HT)-synthesis inhibitor, significantly inhibited the expression of PCA-induced penile erection and ejaculation, while acute spinal transection at thoracic level did not affect the sexual responses. These results indicate that PCA-induced penile erection and ejaculation in anesthetized rats are mainly produced by the release of 5-HT, which is limited to the lower spinal cord and/or the peripheral sites. Furthermore, the sexual responses can be easily and reliably elicited by administration of PCA, which may be useful for the study of the mechanisms underlying male sexual functions.

Animals↗

Effect of Added Salts or Polyols on the Cloud Point and the Liquid-Crystalline Structures of Polyoxyethylene-Modified Silicone.

The effect of added salts (NaCl, Na(2)SO(4), and NaSCN) or polyols (glycerin (Gly), 1,3-butanediol (1,3-BD), ethylene glycol (EG), and polyethylene glycol (PEG400)) on the hexagonal liquid-crystalline structure of polyoxyethylene-modified silicone was investigated by means of small angle X-ray scattering (SAXS). The effective cross-sectional area of the lipophilic part of the aggregate, a(s), in the hexagonal phase decreases upon the addition of salts, on one hand, lowering the cloud point in the dilute aqueous siloxane surfactant solutions. On the other hand, if added salt raises the cloud point, the a(s) increases. Similar results were obtained in the case of the addition of polyols. Since the a(s) mainly depends on the EO chain length, the above results are direct evidence that the hydration or dehydration of the EO chain is affected by these additives. The static fluorescence probe method was applied to the Gly and 1,3-BD systems using 8-anilino-1-naphthalene-sulfonic acid, ANS, to know the change in hydration of the EO chains. In the Gly system, the hydration of the EO chain monotonically decreases whereas 1,3-BD first increases the hydration and then decreases it at high 1,3-BD content. These results are very consistent with the SAXS and cloud temperature results. Copyright 2000 Academic Press.

Journal Article↗