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Biomedical subjects

T Kido

Publications and source records attributed to T Kido.

At least 91 records · Page 5Linked to original sources

Otoconial formation in the chick: changing patterns of tetracycline incorporation during embryonic development and after hatching.

The antibiotic tetracycline (TC) is incorporated into calcifying tissues and serves as a fluorescent marker for identifying calcifying sites in bone and otoconia. Fluorescent labeling was performed at different stages in chick embryos and newly hatched chicks. The stagewise changes in the intensity, location and time course of fluorescent labeling were assessed. TC/egg (1-2 mg) was injected into the yolk sacs of embryos on the 4th, 8th and 11th embryonic days (ED), and the embryos were then killed at specified times after injection. In newly hatched chicks, TC was injected daily intraperitoneally with 0.06 mg TC/g body weight for 7 days and the chicks were killed on the 8th day after hatching. Embryos injected on the 4th ED and killed on the 6th ED showed intense fluorescence in the saccular otoconial layer. All maculae from embryos killed after injection on the 4th ED showed uniformly intense fluorescence throughout the otoconial layer. By the 9th ED, otoconia in all three maculae (saccular, utricular, and lagenar) fluoresced. Maculae from embryos killed after injection on the 8th ED showed uniformly intense fluorescence throughout the otoconial layer or intense localized fluorescence mainly in the upper half of the otoconial layer. All maculae from embryos killed after injection on the 11th ED showed moderate to weak fluorescence primarily in the lower half of the otoconial layer. All maculae from posthatched chicks showed very weak fluorescence throughout the otoconial layer. Otoconia at the periphery of the maculae generally showed weak fluorescence in embryos that had been injected on the 4th and 8th ED, but not in embryos injected on the 11th ED. TC, which competes for calcium binding sites, may inhibit the formation of some otoconia. The formation of giant otoconia may reflect subtle changes in the crystallization microenvironment on these occasions. In brief, the results suggest that: (a) otoconial formation in the saccule precedes that of the utricle and lagena; (b) otoconial formation occurs during the early period (beginning the 6th ED); (c) otoconial formation is stratified, with those in the upper layer forming first and those in the lower layer forming last.

Animals↗

Scanning electron microscopic study of amphibians otoconia.

The otoconia of three adult amphibian species were studied by scanning electron microscopy (SEM). Two calcium carbonate polymorphs (calcite and aragonite) were shown to be present at specific sites in the membranous labyrinth. The utricle contained only calcitic otoconia, whereas the saccule, lagena and endolymphatic sac contained only aragonitic otoconia. SEM examination demonstrated that there is a morphological difference in otoconia according to the site of origin in the membranous labyrinth, and that a mechanism for determining the range of otoconial sizes according to this difference in otoconial morphology may exist.

Amphibians↗

Concentration of cadmium in rice and urinary indicators of renal dysfunction.

OBJECTIVES: (1) To examine the relation between concentrations of cadmium (Cd) in rice and urinary concentrations of indicators of renal dysfunction and the prevalence of abnormalities in urine in areas polluted by Cd. (2) To establish the maximum allowable concentration of Cd in rice from these findings. METHODS: The target population consisted of 1703 inhabitants (832 men and 871 women) aged over 50 years who consumed home grown rice and had lived in the same hamlet in areas polluted by Cd in the Kakehashi River basin in Ishikawa Prefecture, Japan for at least 30 years. The correlation coefficients between concentrations of Cd in rice and several urinary substances, the prevalence of abnormalities in urine and sex in hamlets polluted by Cd were calculated. Finally, regression analysis was performed for significant indicators to calculate the maximum allowable concentration of Cd in rice based on values in a control group. CONCLUSIONS: Significant correlations between concentration of Cd in rice and concentrations of urinary beta 2-microglobulin, metallothionein, glucose, and aminonitrogen were established. Similarly, there were significant correlations between concentration of Cd in rice and the prevalence of beta 2-microglobulinuria, metallothioneinuria, glucosuria, proteinuria, proteinuria with glucosuria, and aminonitrogenuria. The highest maximum allowable concentration of Cd in rice calculated for these indicators was 0.34 ppm/l and 0.29 ppm/g creatinine. Both values are lower than 0.4 ppm, the tentative limit prescribed by the Japanese government.

Aged↗

Effect of human neutrophil elastase on tracheal mucociliary transport in anesthetized quails.

We investigated the effect of human neutrophil elastase (HNE) on tracheal mucociliary transport in anesthetized quails. Topical application of HNE (30-300 microg/kg) to tracheal mucosa dose-dependently decreased mucociliary transport velocity (MCTV). The HNE (300 microg/kg)-induced decrease in MCTV was blocked by ONO-5046 x Na (sodium N-[2-[4-(2,2-dimethylpropionyloxy)phenyl-sulfonylamino]benzo yl]aminoacetate tetrahydrate) (3-30 mg/kg, i.m.), a specific neutrophil elastase inhibitor. Furthermore, we found that HNE increased DNA, fucose and protein contents of tracheal lavages, and the increases were also reverted by ONO-5046 Na. These results indicated that HNE decreased tracheal mucociliary transport, and the decrease may be, at least in part, ascribed to the deterioration of tracheal secretions.

Animals↗

Dexamethasone suppresses mucus production and MUC-2 and MUC-5AC gene expression by NCI-H292 cells.

Excessive production of airway mucus is a characteristic feature of many chronic inflammatory lung diseases. Although current pharmacological approaches to excessive mucus production are limited, glucocorticoids appear to be the most effective among a few useful drugs. The exact evidence for the effectiveness of glucocorticoids on mucus production has not been fully elucidated to date. The purpose of this study is to clarify the effect of dexamethasone on mucus production and mucin gene expression in a human pulmonary mucoepidermoid carcinoma cell line (NCI-H292). NCI-H292 cells produced hyaluronidase-resistant high-molecular-weight glycoconjugates (HMWG), which elute in the void volume on Sepharose CL-4B column chromatography. Dexamethasone significantly suppressed the basal production of [3H]glucosamine-or [3H]serine-labeled HMWG in NCI-H292 cells. In Northern blot analysis, dexamethasone attenuated steady-state mRNA levels of MUC-2 and MUC-5AC mucin genes. These data indicate that dexamethasone suppresses the basal production of HMWG and decreases steady-state mRNA levels of mucin genes in airway mucus-producing cancer cells.

Carcinoma↗

Acid phosphatase activity in the chick's inner ear.

The cellular localization of distribution of acid phosphatase (AP) in the plastic sections of newly hatched chick's inner ear were investigated utilizing an azo-coupling method. AP activity as evidenced by azo dye deposits were well defined and localized in various cells of membranous labyrinth. Intense AP activity was detectable in the supranuclear area of hair cells in the basilar papilla and vestibular sensory hair cells. As in the case of the other sites of AP activity, marked AP activity was seen in the supranuclear area of the transitional epithelia of crista ampullaris and in the supranuclear area, or diffusely in the cytoplasm of the dark cells at the base of crista ampullaris. The columnar cells and the cells of tegmentum vasculosum showed moderate to strong AP activity. The statoacoustic and vestibular ganglion cells showed various degrees of AP activity. On the AP activity of statoacoustic or vestibular ganglion, in comparison between the sections from JB-4 Plus embedded specimens and those from LR White embedded specimen, the latter could more intensely demonstrate AP activity than the former. Moreover, sections fixed in 2.5% paraformaldehyde demonstrated more intense AP activity than those fixed in 2.5% glutaraldehyde.

Acid Phosphatase↗

[A case report--congenital esophago-bronchial fistula with esophageal diverticulum].

Congenital esophago-bronchial fistula with diverticulum is rare, and in Japan only 29 cases have been reported. A 59-year-old man had suffered from recurrent pulmonary infections and often complained of coughing while drinking water during the previous two years. An UGI series for follow-up of gastric ulcer revealed an esophago-bronchial fistula, located between the mid-esophagus and B10 of the right lung. We resected the diverticulum and the fistulous tract with a partial excision of S10. Histological examination revealed that the squamous epithelium with the muscularis mucosa of the esophagus was smoothly connected to the columnar epithelium of the bronchus. Thus, we diagnosed this fistula as congenital, not acquired. Comparison of the previous UGI series before presenting symptoms with that performed at this admission showed the lengthening and thickening of this congenital fistula during the three-years period. We suspected that the influence of acquired factors may cause a congenital fistula to manifest various clinical symptoms.

Adult↗

[Pharmacokinetic and clinical studies on azithromycin in children].

Azithromycin (AZM) is a new oral macrolide antibiotic drug. AZM either in 10% fine granules form or in 100 mg capsule form was studied for its pharmacokinetics and treatment efficacy in pediatric patients with various infections. 1. Pharmacokinetics. Plasma and urine samples were collected from four patients with pharyngitis and post-dosing drug levels were determined. The drug was given once daily at 10 mg/kg body weight for 3 days. The drug concentrations found in plasma at 96 hours after the first dosing (48 hours after the final dosing) lay in a range of 0.02 and 0.04 microgram/ml and in urine at 120 hours after the first dosing (72 hours after the final dosing) in a range between 3.2 and 7.7 micrograms/ml. AZM was found in two patients but no effect was observed on blood levels of theophylline determined between 48 and 96 hours after the first dosing in the treatment of underlying bronchial asthma. 2. Clinical study results. Clinical studies of AZM was carried out in 25 pediatric patients with bacterial infections that mainly affected the respiratory tract. The patients received either 10% fine granules at 10 or 20 mg/ kg body weight or 100 mg capsules at 10 mg/kg body weight once daily over 3 to 6 days. The drug was found markedly effective in six patients, moderately effective in thirteen patients, while the investigators could not assess the drug efficacy in six patients. Although no side effect was reported in the study, two patients experienced slight decrease in WBC.

Adolescent↗

Ligand western blotting for specific detection of active forms of proteases.

We developed a non-radioactive method of ligand western blotting for specific detection of active forms of serine proteases. The method consists of three steps: (i) separation of proteins by electrophoresis in sodium dodecyl sulfate-polyacrylamide gel, followed by blotting of proteins to nitrocellulose membrane; (ii) binding of a specific ligand, such as soybean trypsin inhibitor labeled with biotin, to protease on the membrane; and (iii) detection of the protease-inhibitor complex by color reaction (or chemiluminescence) developed by streptavidin-conjugated peroxidase (or alkaline phosphatase). By using this method, plasmin and trypsin (serine proteases) were detected, but papain (thiol protease) or pepsin (acidic protease) was not. Plasmin was detectable up to less than 4 ng. Inactive precursors of serine protease, i.e. plasminogen and trypsinogen, did not exhibit visible bands until they were activated by treatment with streptokinase or trypsin, respectively. We applied this method to clinical samples, and succeeded in detecting plasminogen, after conversion to plasmin with streptokinase treatment, in as little as 5 microliters of serum or trypsin, as it was in 10 microliters of pancreatic juice.

Bacterial Proteins↗

Processing of proendothelin-1 by human furin convertase.

Endothelin-1 (ET-1) is the most potent vasoactive peptide known to date. The peptide is initially synthesized as an inactive precursor (proET-1) which undergoes proteolysis at specific pairs of basic amino acids to yield bigET-1. Production of ET-1 then proceeds by cleavage of bigET-1 by the endothelin converting enzyme (ECE). Here, we demonstrate that the in vitro cleavage of proET-1 by furin, a mammalian convertase involved in precursor processing, produced bigET-1. Upon further processing, bigET-1 was converted to biologically active ET-1. Furthermore, we demonstrate that the furin inhibitor, decanoyl-Arg-Val-Lys-Arg chloromethylketone, abolished production of ET-1 in endothelial cells.

Amino Acid Chloromethyl Ketones↗

Cell differentiation induced by poly(ADP-ribose) synthetase inhibitors.

From a survey of about 400 compounds, we found a number of potent and specific inhibitors of poly(ADP-ribose) synthetase. Two new classes of inhibitors include vesnarinones and heterocyclic amines. Although the inhibitory activity was not very strong, several of these classes of inhibitors proved to induce most efficiently differentiation of murine teratocarcinoma EC cells in culture; for example, 70 microM benzylvesnarinone or 1 mM PhIP effected almost complete change in cell morphology in 5 to 7 days. Analyses of poly(ADP-ribose) synthesis and NAD concentrations in EC cells after treatment with a differentiation inducer suggested that poly(ADP-ribose) might play a role at an initiation stage of cell differentiation.

Animals↗

Significance of elevated urinary human intestinal alkaline phosphatase in Japanese people exposed to environmental cadmium.

Urinary human intestinal alkaline phosphatase (IAP), beta 2-microglobulin (beta 2-MG) and N-acetyl-beta-D-glucosaminidase (NAG) were analyzed in 40 Japanese environmental-cadmium (Cd)-exposed and 40 non-exposed subjects to evaluate early biological markers for Cd-induced renal damage. All urinary indicators were significantly higher in the Cd-exposed subjects than non-exposed subjects. A fourth-order function was fitted for the relationship between beta 2-MG and IAP or NAG. The beta 2-MG concentration corresponding to the inflexion point for IAP was smaller than that for NAG. This result may support the contention that the cells containing IAP are damaged earlier than those containing NAG, and that IAP is a useful marker for detecting renal tubular dysfunction in people moderately exposed to Cd. However, in the stage of severe renal damage, the combination of IAP and beta 2-MG is considered to be more useful.

Acetylglucosaminidase↗

Characterization of a dopamine-releasing action of 6R-L-erythro-tetrahydrobiopterin: comparison with a 6S-form.

6R-L-erythro-Tetrahydrobiopterin (6R-BH4) is a cofactor for aromatic L-amino acid hydroxylases and nitric oxide synthase. Recently, we have reported that independently of its cofactor activities, 6R-BH4 acts from the outside of neurons in the brain to enhance the release of monoamine neurotransmitters such as dopamine. To characterize the pharmacological properties of the action, we examined the effects of 6S-BH4, a diastereoisomer of 6R-BH4, on dopamine release in the rat striatum by using brain microdialysis and compared its effects with those of 6R-BH4. Perfusion of 6S-BH4 or 6R-BH4 through the dialysis probe increased extracellular dopamine levels (an index of in vivo dopamine release) concentration dependently; the maximal increase by 6S-BH4, was one-sixth of that by 6R-BH4. 6S-BH4 increased extracellular DOPA levels in the presence of NSD 1015, an inhibitor of aromatic L-amino acid decarboxylase (an index of in vivo tyrosine hydroxylase activity), to an extent similar to the increase induced by 6R-BH4. The increase in the DOPA levels induced by either of the pteridines was abolished after pretreatment of rats with alpha-methyl-p-tyrosine (an inhibitor of tyrosine hydroxylase). Under the same conditions, the 6S-BH4-induced dopamine release was abolished, but most of the 6R-BH4-induced increase persisted. Coadministration of 6S-BH4 with 6R-BH4 inhibited the increase in dopamine release induced by 6R-BH4 alone. These results show that 6R-BH4 stimulates dopamine release by acting at the specific recognition site on the neuronal membrane, and that 6S-BH4 acts as an antagonist of 6R-BH4 at this site, although it has cofactor activities.

Animals↗

[Studies on health effects of cadmium exposure in the general environment].

Effects of exposure to cadmium (Cd) in the general environment on health have been studied in several Cd-polluted areas in Japan. In this paper, results of investigations in the Kakehashi River basin, Ishikawa, a Cd-polluted area, are mainly reviewed as follows. 1. In an epidemiological study, prevalences of beta 2-microglobulinuria (beta 2-MG-uria) were 14. 3 and 18.7% in Cd-exposed men and women over 50 years of age, respectively, when a cutoff level of beta 2-MG of 1000 micrograms/g.cr. was used. These values are significantly high compared with those of nonexposed subjects. 2. Using several urinary indicators of renal function, such as alpha 1-microglobulin, N-acetyl-beta-D-glucosaminidase, human intestinal alkaline phosphatase, mucoprotein and albumin, levels of all indicators were significantly higher in Cd-exposed subjects than in nonexposed subjects. Furthermore, in a 5-year follow-up study, irreversibility of Cd-induced renal damage was shown after the level of beta 2-MG rose above 1000 micrograms/g.cr. 3. Exposure to Cd caused marked osteopenia, in particular in women, as assessed by microdensitometry, and this osteopenia was significantly associated with Cd-induced renal dysfunction. Serum 1 alpha, 25 dihydroxy-vitamin D levels were lower and serum parathyroid hormone (PTH) levels were higher in Cd-exposed subjects with renal damage than in nonexposed subjects. We assume that disturbances in vitamin D and PTH metabolism may be one of the causative factors for Cd-induced bone damage. 4. The dose-response relationships between Cd exposure and renal dysfunction were assessed using several statistical methods such as simple linear regression, probit linear regression, logistic regression analysis and general linear models. The prevalences of beta 2-MG-uria or metallothioneinuria were employed as indices of health effects, while urinary Cd and total Cd intake was used as indicators of Cd exposure. As the biological threshold, urinary Cd concentrations were calculated to be 3.8-4.2 micrograms/g.cr. in men and 3.8-4.8 micrograms/g.cr. in women, and a maximum allowable intake of about 2 g Cd is considered to be a reasonable estimate for preventing Cd-induced renal dysfunction. 5. A significant association was found between urinary beta 2-MG and mortality in a 9-year follow-up study of 3178 Cd-exposed inhabitants, using Cox's proportional hazards model. Moreover, mortality rates increased in proportion to increases in the amount of urinary beta 2-MG excreted. These results suggest that the prognosis for Cd-exposed subjects with renal tubular dysfunction is unfavorable.

Aged↗