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Biomedical subjects

F Kayama

Publications and source records attributed to F Kayama.

At least 37 records · Page 2Linked to original sources
PubMed1995

Cadmium-induced renal damage and proinflammatory cytokines: possible role of IL-6 in tubular epithelial cell regeneration.

Cadmium exposure in humans and experimental animals produces renal damage characterized by degeneration and necrosis of tubular epithelial cells followed by interstitial inflammation and eventual regeneration of proximal tubular cells. Since chronic kidney diseases are often associated with the presence of inflammatory cytokines and cadmium has been reported to alter cytokine expression in monocytes and the Kupffer cells of the liver, we investigated the role of proinflammatory cytokines in cadmium-induced nephrotoxicity. Increases in TNF-alpha and IL-6 cytokine mRNA transcripts and secretion were observed in the kidney following exposure of LPS-primed mice to a total of 21 mg/kg body weight cadmium administered over a 14-week period. IL-6 was the predominant cytokine expressed and was found to be present in mesangial cells. Cadmium, in the presence of LPS, was able to induce IL-6 secretion in vitro from mouse glomerular mesangial cells. Proliferative cell nuclear antigen (PCNA) staining revealed increases in regeneration of tubular epithelial cells following cadmium exposure. Furthermore, renal tubular epithelial cells responded to IL-6 by marked proliferation. Taken together, these data suggest that cadmium-induced IL-6 secretion in the kidney may act to support the regeneration of renal tubular epithelial cells that occurs in the course of cadmium nephrotoxicity.

Animals↗
PubMed1994

[The effect of occult hyperprolactinemia (OHP) on gonadotropin secretion system].

The present study was conducted to investigate the effects of the transient increase of serum prolactin levels on the gonadotropin secretion system in patients with occult hyperprolactinemia (OHP). 216 cases of normoprolactinemic hypothalamic anovulatious were selected by LH-RH and TRH loading tests, and 5mg/day of bromocriptine was administered for more than 8 weeks. The effectiveness of the bromocriptine administration was estimated by the ultrasonic examination of the follicular development. The endocrinological backgrounds were compared between bromocriptine effective (154 cases, group A) and non-effective (62 cases, group B) patients. Serum prolactin levels 30min. after LH-RH and TRH loading (PRL30 in group A were significantly higher than those of group B (74.1 +/- 36.5 vs. 38.0 +/- 18.2ng/ml, p < 0.01). From this result, it was thought that many of the OHP patients were selected in group A. Serum LH levels 30min. after loading test (LH30) in group A also increased compared to those of group B (65.0 +/- 66.5 vs. 43.1 +/- 34.3mIU/ml, p < 0.02). The LH/FSH ratio before loading was also higher in group A (1.3 +/- 0.6) than that of group B (1.0 +/- 0.5, p < 0.02). This fact showed that group A also contained patients with hyper-LH hypothalamic anovulation, which is known as the endocrinological PCOD. There were also significant inverse correlations between serum levels of prolactin and FSH in group A (before loading values: r = 0.272, 30min. after loading: r = 0.224, p < 0.01). By the administration of bromocriptine, serum prolactin levels decreased both in group A and B, and the elevated serum LH/FSH ratio (1.0 +/- 0.4, p < = 0.02), LH30 (46.1 +/- 37.0mIU/ml, p < 0.005) also decreased significantly. Serum levels of FSH in group A increased significantly with treatment (before loading: 5.4 +/- 2.6-->6.2 +/- 2.0, 30min. after loading: 10.6 +/- 6.0-->14.6 +/- 9.9mIU/ml, p < 0.005). From these facts, it was concluded that FSH secretion was suppressed even by a slight increase of serum prolactin levels which was usually seen in the OHP, and bromocriptine administration was effective not only for the suppression of serum prolactin and LH levels, but also for the improvement of FSH secretion in the OHP patients.

Anovulation↗
PubMed1994

Cytokine induction in human epidermal keratinocytes exposed to contact irritants and its relation to chemical-induced inflammation in mouse skin.

In response to exogenous stimuli such as phorbol-12-myristate 13-acetate, ultraviolet B radiation, and lipopolysaccharide, human keratinocytes produce soluble mediators that are important in primary contact irritancy including cytokines that are associated with proinflammatory properties (interleukin-1 alpha [IL-1 alpha], tumor necrosis factor alpha), chemotaxis (IL-8), and growth activation (granulocyte/macrophage colony stimulating factor, IL-6, transforming growth factor alpha). We examined qualitative and quantitative changes in selected intracellular and secreted cytokines in human keratinocyte cultures in response to non-sensitizing contact irritants (croton oil, sodium lauryl sulfate, methyl salicylate, ethyl phenylpropiolate), sensitizing irritants (oxazolone, dinitrofluorobenzene), and ulcerative agents (phenol, benzalkonium chloride, chromium trioxide). The chemicals were also applied to mouse skin to assess whether the chemical-specific pattern of inflammation correlated with the in vitro production of keratinocyte-derived cytokines. Although all agents elicited neutrophils to the site of chemical application, time dependent and chemical-specific patterns of inflammation could be detected. Sodium lauryl sulfate, phenol, and croton oil induced increases in IL-8 production at non-cytotoxic concentrations in semi-confluent human keratinocyte cultures. Phenol and croton oil stimulated tumor necrosis factor alpha production, whereas croton oil was the only agent found to induce granulocyte/macrophage colony-stimulating factor production. Croton oil, phenol, benzalkonium chloride, and dinitrofluorobenzene induced the intracellular production of IL-1 alpha without a concomitant release into the medium. The release of cytokines occurred in parallel with a relative increase in cytokine-specific mRNA transcripts. Studies using neutralizing antibodies to tumor necrosis factor alpha and IL-1 alpha demonstrated that IL-8 induction by croton oil and phenol occurred directly rather than through autocrine circuits. These data suggest that a given pattern of cytokine production is chemical-specific and may predict the contribution of keratinocytes to skin inflammation.

Animals↗
PubMed1994

Endotoxin-induced cytokine gene expression and excretion in the liver.

Peptide mediators, including tumor necrosis factor-alpha, interleukin 1 and interleukin-6, are associated with many chronic inflammatory diseases and septic shock. As such, considerable information has been collected by means of study of cytokine secretion from isolated cells or plasma cytokines during septic shock or inflammatory disorders. In this investigation, we used semiquantitative polymerase chain reaction analysis and a recently developed liver slice model to examine the characteristics of cytokine profiles that occur in the liver, the main organ involved in endotoxemia, after lipopolysaccharide challenge. Tumor necrosis factor-alpha, interleukin-1 alpha and interleukin-6 were rapidly secreted after in vivo LPS exposure or when added in vitro to rodent or human liver slice samples. This increase was associated with increased cytokine-specific mRNA transcripts. Kinetic analysis revealed that most tumor necrosis factor-alpha is released from the liver within 1 hr of lipopolysaccharide challenge, whereas interleukin-1 alpha and interleukin-6 continued to be produced for the entire culture period. Addition of monoclonal antibodies against tumor necrosis factor-alpha or interleukin-1 alpha to the culture partly inhibited interleukin-6 secretion, indicating that interleukin-1 alpha and tumor necrosis factor-alpha help mediate and sustain interleukin-6 synthesis. Depletion of hepatic sinusoidal macrophages (Kupffer cells) by a liposome-mediated macrophage "suicide" technique indicated that almost all of the secreted interleukin-1 alpha and tumor necrosis factor-alpha originate from these cells, whereas interleukin-6 secretion might also include other cell types. This study supports and extends previous findings and allows for a more rational approach to developing effective therapies against chronic inflammatory diseases and septic shock.

Alanine Transaminase↗
PubMed1993

Effect of side-stream cigarette smoke on the hepatic cytochrome P450.

The effect of inhalation of side-stream cigarette smoke on the hepatic microsomal cytochrome P450 was investigated Rats were placed in a chamber of 0.1 m3 in volume, in which cigarettes were burned at the rate of 1, 3, or 5 cigarettes per h, 8 h/day for 5 days. Cytochrome P450 and NADPH-cytochrome c reductase showed no significant changes; however, cytochrome b5 increased significantly. On the other hand, the activity of aryl hydrocarbon hydroxylase (AHH) decreased in the rats treated with a high concentration of cigarette smoke. In order to study the changes of isoforms of cytochrome P450, western blot analyses were performed. The inductions of three kinds of isoforms, cytochromes P450IA1, IA2, and IIB1, were demonstrated immunochemically. However, there were disagreements between the results of the western blot analyses and the measurements of total cytochrome P450 content and AHH activity.

Animals↗
PubMed1993

Personal exposure to nitrogen dioxide from indoor heaters and cooking stoves.

The personal exposure to NO2 generated from various heaters and cooking stoves were studied, using 85 university students. The students attached NO2 filter badges to their chests or collars and wrote down the period of time for heating and cooking for 1 week. Types of heaters and smoking habits were described through a questionnaire. The urinary hydroxyproline/creatinine ratio (HOP/C) was examined as a biomarker for health effects. The outdoor NO2 concentration during the study period was 13.5-13.7 micrograms/m3. Smoking and the usage of electric heaters did not affect the exposure to NO2. Exposure increased according to the length of time kerosene heaters or oil fan heaters were used. The NO2 concentration during the heating by a kerosene heater and an oil fan heater was calculated to be 219 and 474 micrograms/m3, respectively. The correlation between the period of cooking and personal exposure was also observed. The NO2 levels during cooking were calculated to be 290 micrograms/m3. Using these calculated values of NO2 concentration, it is possible to presume the personal exposure levels from the length of time heaters and cooking stoves are used even if the subjects do not attach the filter badges. Neither smoking nor exposure to NO2 were associated with the increase of urinary HOP/C.

Adult↗
PubMed1992

The effect of ethylene glycol monomethyl ether and diethylene glycol monomethyl ether on hepatic gamma-glutamyl transpeptidase.

In this paper, we determined whether ethylene glycol monomethyl ether (EGME) and diethylene glycol monomethyl ether (diEGME) induce hepatic gamma-glutamyl transpeptidase activity. Male adult Wistar rats weighing 220 g were used as experimental animals. EGME (100, 300 mg/kg per day) and diEGME (500, 1000, 2000 mg/kg per day) were administered by gavage for 1, 2 or 5 days or 4 weeks. In the 4-week study, experimental animals were administered EGME or diEGME once a day orally, 5 days/week. EGME treatment increased the serum gamma-glutamyl transpeptidase (GGT) level significantly, however, diEGME did not. The activities of three other enzymes (SGOT, SGPT and ALP) in serum were not altered by EGME or diEGME treatment and thus there was no biochemical indices of hepatic damage by EGME or diEGME. EGME treatment increased the GGT activities in the liver and lungs. Of the organs examined, the induction of GGT was the greatest in the liver. The inducibility in the liver was 216% for the 5-day treatment and 460% for the 4-week treatment. A dose-dependent increase of hepatic microsomal GGT activity by EGME was observed. On the other hand, renal GGT activities were declined to 72% and 60% of control by the 5-day and 4-week EGME treatments, respectively. DiEGME did not affect the GGT activities in any of the tissues except those of the brain. In the histochemical study, most hepatocytes at the periportal zones were stained with GGT staining after the 4-week treatment. However, the hepatocytes at the central zones were negative.

Animals↗
PubMed1991

Absorption of cadmium after a long-term oral administration of cadmium to dogs.

A long-term experiment using beagle dogs to investigate the absorption of cadmium was conducted. The dogs in the experimental groups were given a commercial diet and pelleted food containing 1, 3, 10, 50, and 100 mg of cadmium per day. The cadmium concentration in the blood increased continuously, gradually reaching a steady state following the administration of cadmium. The cadmium excreted daily in urine increased continuously. The cumulative excreted amount of cadmium in urine was calculated by using the trapezoidal rule based on the data of excretion of cadmium in urine. Then the absorbed fraction of administered cadmium was estimated on the basis of the relationship between the cumulative excreted amount of cadmium in urine and the cumulative administered dose of cadmium after the cadmium concentration in blood reached a steady state. The absorbed fraction of cadmium decreased with an increase in the administered dose of cadmium. A dose-dependent increase between the absorbed amount and the administered dose was observed.

Administration, Oral↗
PubMed1991

Selective depletion of immature thymocytes by oral administration of ethylene glycol monomethyl ether.

Although immunotoxicity of ethylene glycol monomethyl ether (EGME) has been strongly suspected, functional evaluation of the immune response in EGME-treated animals was negative in previous studies. We observed a decrease in thymic cellularity and increases in the various ex vivo immunological assays in mice, orally administered with EGME 0.5 or 1.0 mg/g body weight daily for 5 or 10 days: ex vivo lymphoproliferative responses to concanavalin A, in vitro induction of trinitrophenyl (TNP)-specific cytotoxic T-cell activity of thymocytes and splenocytes. Histopathological examination of the thymus of the treated mice disclosed a markedly atrophic cortex and almost intact thymic medulla. Study of thymocyte surface markers revealed that CD4+/CD8+, Thy-1+, PNA+ immature thymocytes were relatively decreased in EGME-gavaged mice and that, thus, ratios of CD4-/CD8+, H2+ mature thymocytes were enriched. These findings indicate that oral administrations of EGME selectively deplete immature thymocytes in mice. Although the mechanism of action remains unknown, the EGME-induced immature thymocyte depletion is not considered to be due to lymphocidal action of corticosteroids.

Administration, Oral↗
PubMed1991

Effects of dietary zinc deficiency on protein secretory functions of the mouse testis.

The effects of dietary zinc deficiency on testicular protein secretion, mainly that by Sertoli cells, were examined by electron microscopy and two-dimensional polyacrylamide gel electrophoresis of [35S] methionine-labeled secretory proteins from mouse testes. Zinc deficiency caused a significant decrease in the gonadosomatic index and a distinct increase in deoxyribonucleic acid concentration. Sertoli cells maintained normal fine-structural features; junctional complexes among Sertoli cells continued to divide seminiferous tubules into basal and adluminal compartments in the zinc-deficient mouse testes. Severe atrophic changes were observed in spermatogenic cells after meiotic division in the adluminal compartment, but not in spermatogonia located in the basal compartment. Zinc replacement treatment caused spermatogenesis to recover normally. Although total protein secretion was not affected by zinc deficiency, one polypeptide spot appeared due mainly to the loss of its target spermatogenic cells. The present study indicates that zinc is indispensable for spermatogenic cells after meiosis and that testicular protein secretory functions can be preserved in the absence of zinc.

Animals↗
PubMed1990

Effect of ethylene glycol monomethyl ether and diethylene glycol monomethyl ether on hepatic metabolizing enzymes.

Glycol ethers have been extensively used in industry over the past 40-50 years. Numerous studies on the toxicity of glycol ethers have been performed, however, the effects of glycol ethers on the hepatic drug metabolizing enzymes are still unknown. We studied the changes of the putative metabolic enzymes, that is, the hepatic microsomal mixed function oxidase system and cytosolic alcohol dehydrogenase, by the oral administration of diEGME and EGME. Adult male Wistar rats were used. DiEGME was administered orally; 500, 1000, 2000 mg/kg for 1, 2, 5 or 20 days and EGME was 100, 300 mg/kg for 1, 2, 5 or 20 days. Decreases in liver weights were produced by highest doses of diEGME (2000 mg/kg body wt/day for 20 days) and EGME (300 mg/kg body wt/day for 20 days). DiEGME increased hepatic microsomal protein contents and induced cytochrome P-450, but not cytochrome b5 or NADPH-cytochrome c reductase. The activity of cytosolic ADH was not affected by diEGME administration. On the other hand, EGME did not change cytochrome P-450, cytochrome b5 or NADPH-cytochrome c reductase. The activity of cytosolic ADH was increased by repeated EGME treatment. Therefore it is suspected that the enzyme which takes part in the metabolism of diEGME is different from that of EGME, although diEGME is a structural homologue of EGME.

Administration, Oral↗
PubMed1989

[Continuing education and residency program of occupational medicine in U. S. A].

To investigate postgraduate education of occupational medicine in the U. S. A., the author was sent to take some courses in occupational medicine continuing education supported by the National Institute of Occupational Health (NIOSH) in February and March of 1988. The course participants were mainly industrial hygienists. The contents of the courses were approximately the same as those of the Three-Month Course in Fundamental Occupational Health held in UOEH for medical doctors. The physicians in occupational medicine in the U. S. A. take mainly mini-residency courses from the NIOSH programs. The Curriculum of the Intensive Residency Program at the University of California San Francisco (UCSF) is presented in this report as a reference. According to the information I acquired, well-trained industrial hygienists are maintaining a high standard of control over the workplace environment. I received the impression that the industrial hygienists are playing an important part in occupational health in the U. S. A. Physicians specializing in occupational medicine are interested more in the clinical diagnosis of occupational diseases than in preventive measures such as environmental control of the workplace.

Curriculum↗
PubMed1989

Significance of cardiovascular malformations in cystic hygroma: a new interpretation of the pathogenesis.

Fetuses with cystic hygroma or loose skin of the neck were studied chromosomally and phenotypically to clarify the relation between neck abnormality and cardiovascular malformations. Of 12 fetuses, 9 had chromosome abnormalities: 4 with 45,X, 3 with trisomy 21, one each with trisomy 13, dup 6q. One had normal chromosomes. Two cases, in which chromosome analysis was unsuccessful, were morphologically suspected to be trisomy 13. Nine of the 12 fetuses had either bilateral cystic hygroma of the neck (7 cases) or nuchal bleb (2 cases: trisomy 13 and dup 6q). Two of the 3 remaining cases (trisomy 21) had loose skin of the neck, and one had edematous swelling of the skin of the neck. Except for the last case of trisomy 21, 11 fetuses (91.7%) had severe and/or rare cardiovascular malformations. They were divided into 3 major groups: a) spectrum of hypoplastic left heart syndrome (45,X and dup 6q), b) double outlet right ventricle, agenesis of semilunar valve (trisomy 13), and c) abnormality of atrioventricular orifice or valves (trisomy 21). One fetus with normal chromosomes had persistent left superior vena cava instead of absent right one and calcification of myocardium. Histological observation of edematous skin demonstrated the abnormal distribution of lymph vessels, including their absence. Some cases showed hypoplastic thymus. To integrate the findings of the present study and the descriptions in the literature, a pathogenesis is hypothesized in relation to migration of neural crest cells and extracellular matrix.

Abnormalities, Multiple↗
PubMed1988

[Neonatal hyperbilirubinemia of inadequately breast-fed infants and the effect of formula supplementation].

One hundred and fifty full-term breast-fed infants were analysed for their oral intake in the first 6 days. Fifty infants with less than 330 ml/kg/6 days breast feeding were defined as inadequately breast-fed infants. Twenty inadequately breast-fed infants without formula supplementation had significantly lower total fluid intake, lower total calorie intake, more body weight loss and significantly higher rates of hyperbilirubinemia and requirement of phototherapy when compared with the control group of 100 infants with more than 330 ml/kg/6 days breast feeding. On the other hand, 30 inadequately breast-fed infants with formula supplementation had significantly higher total fluid intake, higher total calorie intake, lower body weight loss and requirement of phototherapy than those without formula supplementation. From these data, we suggest that (1) Inadequate feeding may be a factor responsible for the higher prevalence of early neonatal jaundice in breast-fed infants reported in the literature. (2) Lower fluid intake, lower calorie intake and greater body weight loss may be associated with the higher incidence of hyperbilirubinemia and requirement of phototherapy. (3) Formula supplementation may be helpful in decreasing the risk of hyperbilirubinemia in inadequately breast-fed infants.

Breast Feeding↗
PubMed1985

[Reliability of the advice given at genetic counselling: follow-up study].

A follow up investigation was carried out in order to estimate the reliability of the advice given at our genetic counselling clinic. Data were collected mainly by questionnaires sent by mail in November, 1983 to 556 clients counselled during the period January, 1976 - December, 1982. The outcome of 444 pregnancies for 361 clients was revealed. They were divided into three groups according to the risks estimated and suggested by the counsellors; below 2% (Group I), 2 - 9% (Group II) and 10% or more (Group III). The following results were obtained. The incidence of those who had not become pregnant following the day of counselling was higher in Groups II and III than in Group I. The rate of spontaneous abortion was higher in Group III than in Groups I and II. The incidence of pregnancies with children affected by birth defects for which the risks were estimated was 1.5% in Group I, 6.5% in Group II and 26.5% in Group III. Six to nine percent of babies of all groups suffered from other diseases such as intrauterine fetal death, congenital anomalies, developmental abnormalities or severe infectious diseases. The recurrence rate for regular trisomic Down's syndrome was 1.8%. These results suggested that the risk estimates and advice were quite reliable and helpful.

Abortion, Spontaneous↗