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Biomedical subjects

K Yamazaki

Publications and source records attributed to K Yamazaki.

At least 19 recordsLinked to original sources

Effects of the catechol-O-methyltransferase inhibitor tolcapone in Parkinson's disease: correlations between concentrations of dopaminergic substances in the plasma and cerebrospinal fluid and clinical improvement.

We compared the concentrations of dopaminergic substances in the plasma and cerebrospinal fluid (CSF) with clinical severity in patients with Parkinson's disease (PD) under L-dopa/carbidopa treatment and under L-dopa/carbidopa+tolcapone treatment. Compared with treatment with L-dopa/carbidopa alone, the co-administration of tolcapone produced a significant decrease in clinical severity; a remarkable reduction in the 3-O-methyldopa (3-OMD) concentration and significant increase in the L-dopa concentration both in the plasma and CSF; and a significant increase in the dopamine concentration in the CSF. The clinical effects of tolcapone were closely correlated with the reduction in the 3-OMD concentration, but not with the increase in the dopamine and L-dopa concentrations in the CSF.

3,4-Dihydroxyphenylacetic Acid

Evidence suggesting that the odortypes of pregnant women are a compound of maternal and fetal odortypes.

Odortypes--namely, body odors that distinguish one individual from another on the basis of genetic polymorphism at the major histocompatibility complex and other loci--are a fundamental element in the social life and reproductive behavior of the mouse, including familial imprinting, mate choice, and control of early pregnancy. Odortypes are strongly represented in urine. During mouse pregnancy, an outcrossed mother's urine acquires fetal major histocompatibility complex odortypes of paternal origin, an observation that we took as the focus of a search for odortypes in humans, using a fully automated computer-programmed olfactometer in which trained rats are known to distinguish precisely the odortypes of another species. Five women provided urine samples before and after birth, which in each case appropriately trained rats were found to distinguish in the olfactometer. Whether this olfactory distinction of mothers' urine before and after birth reflects in part the odortype and hence genotype of the fetus, and not just the state of pregnancy per se, was tested in a second study in which each mother's postpartum urine was mixed either with urine from her own infant or with urine of a different, same-aged infant. Responses of trained rats were more positive with respect to the former (congruous) mixtures than to the latter (incongruous) mixtures, implying that, as in the mouse, human fetal odortypes of paternal genomic origin are represented in the odortype of the mother, doubtless by circulatory transfer of the pertinent odorants.

Animals

Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin.

BACKGROUND: Prostate cancer is the most common cancer diagnosed in U.S. men and remains incurable once it has metastasized. Many stages of the metastatic cascade involve cellular interactions mediated by cell surface components, such as carbohydrate-binding proteins, including galactoside-binding lectins (galectins). Modified citrus pectin (pH-modified), a soluble component of plant fiber derived from citrus fruit, has been shown to interfere with cell-cell interactions mediated by cell surface carbohydrate-binding galectin-3 molecules. PURPOSE: The aim of this study was to determine whether modified citrus pectin, a complex polysaccharide rich in galactosyl residues, could inhibit spontaneous metastasis of prostate adenocarcinoma cells in the rat. METHODS: The ability of modified citrus pectin to inhibit the adhesion of Dunning rat prostate cancer MAT-LyLu cells to rat endothelial cells was measured by 51Cr-labeling. Modified citrus pectin inhibition of MAT-LyLu cell anchorage-independent growth was measured by colony formation in agarose. The presence of galectin-3 in rat MAT-LyLu cells and human prostate carcinoma was demonstrated by immunoblotting and immunohistochemistry. One million MAT-LyLu cells were injected subcutaneously into the hind limb of male Copenhagen rats on day 0. Rats were given 0.0%, 0.01%, 0.1%, or 1.0% (wt/vol) modified citrus pectin continuously in their drinking water (from day 4 until necropsy on day 30). The number of MAT-LyLu tumor colonies in the lungs were counted. RESULTS: Compared with 15 or 16 control rats that had lung metastases on day 30, seven of 14 rats in the 0.1% and nine of 16 rats in the 1.0% modified citrus-pectin group had statistically significant (two-sided; P < .03 and P < .001, respectively) reductions in lung metastases. The lungs of the 1.0% modified citrus pectin-treated rats had significantly (two-sided; P < .05) fewer metastatic colonies than control groups (9 colonies +/- 4 [mean +/- SE] in the control group compared with 1 colony +/- 1 in the treated group). Modified citrus pectin had no effect on the growth of the primary tumors. In vitro, modified citrus pectin inhibited MAT-LyLu cell adhesion to rat endothelial cells in a time- and dose-dependent manner as well as their colony formation in semisolid medium. CONCLUSIONS: We present a novel therapy in which oral intake of modified citrus pectin acts as a potent inhibitor of spontaneous prostate carcinoma metastasis in the Copenhagen rat. IMPLICATIONS: Further investigations are warranted to determine the following: 1) the role of galectin-3 in normal and cancerous prostate tissues and 2) the ability of modified citrus pectin to inhibit human prostate metastasis in nude mice.

Adenocarcinoma

Ultrastructural evidence of cell communication between epithelial dark cells and melanocytes in vestibular organs of the human inner ear.

BACKGROUND: The possibility of interaction between epithelial dark cells and melanocytes in the mammalian inner ear has been pointed out because of their morphological and biochemical characteristics, although very few studies have dealt directly with communication between these two types of cells. We investigated the dark cell area of human vestibular organs in order to clarify the ultrastructural evidence for cell interaction between epithelial dark cells and melanocytes. METHODS: All of the material was obtained from vestibular schwannoma operations. Paraffin sections were stained with hematoxylin and eosin (H&E) and by the Fontana-Masson technique. Other paraffin sections were also stained immunohistochemically for S-100 protein. Glutaraldehyde fixed specimens were investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS: Light microscopy revealed melanin pigment granules in the cytoplasm of epithelial dark cells. Melanocytes in the subepithelial layer stained positively for S-100 protein. The presence of intraepithelial melanocytes was confirmed by the presence of cell profiles with a large number of melanin pigment granules and S-100 protein in the cytoplasm. SEM showed that the dark cells had a pentagonal surface with microvilli on the apical surface edge. They had complicated structures at the basal portion of their cytoplasm. Melanocytes extending cytoplasmic processes to adjacent areas were observed under the dark cells. TEM showed that the dark cells were tightly linked by junctional complexes in the upper lateral portion of their cytoplasmic membrane and interdigitated by lateral infoldings. Compound melanosomes (phagosomes or secondary lysosomes) found in the cytoplasm of the dark cells contained poorly pigmented melanosomes with a periodic internal structure. Gap junctions were clearly showed between adjacent melanocytes in the subepithelial layer. CONCLUSIONS: The characteristic substructures of dark cells and melanocytes suggested the presence of intimate cell interaction between these two types of cells in the vestibular organs of the human inner ear, although it is not clear at this stage whether such cell interaction is specific only for patients with vestibular schwannoma. Dark cells and melanocytes form a cell community that serves to maintain homeostasis in vestibular organs through communication in which cell information obtained by both dark cells and melanocytes serves to facilitate the system.

Adult

Assessment of spine bone mineral density in ovariectomized rats using DXA.

Measurements of lumbar spine (L1-L6) bone mineral density (BMD) and bone mineral content (BMC) of Wistar rats were obtained by dual energy X-ray absorptiometry (DXA) (QDR-1000W, Hologic Inc., Waltham, MA) to estimate reproducibility and investigate age-related changes. In addition we evaluated the accuracy of the technique in female rats. The coefficients of variation (CV) for spine BMD measurements were found to range from 0.73-1.04 in vivo and from 0.36-1.56 in vitro. The in vitro measurements were performed in a 3 cm deep water bath to stimulate an equivalent tissue thickness. Spine BMC, measured in vivo and in vitro correlated closely with the subsequently determined ash weights (r2 = 0.87 and 0.97, respectively). We examined age-related spine BMD by DXA. A relatively constant increase in spine BMD was observed from 6 weeks to 22 weeks; spine BMD remained stable between 22 and 58 weeks. No peak was observed in spine BMD. To evaluate the effect of estrogen deficiency on animals of different ages, we measured spine BMD weekly in female rats subjected to ovariectomy (OVX) or sham operation at 8 and 23 weeks of age. The spine BMDs in each OVX rat were significantly lower than that of the controls. In the 23-week-old rats, bone loss was quite rapid for the first 3 weeks of observation and stable afterward. The BMD of 8-week-old OVX rats increased with body size. We conclude that DXA allows the observation of age-related changes in the spine BMD of rats with great precision.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon

A study of intercellular relationships between trabecular bone and marrow stromal cells in the murine femoral metaphysis.

The cellular relationship between the substantia spongiosa of bone (cancellous or trabecular bone) and the haematopoietic bone marrow in the femoral metaphysis of C57BL/6NJCL mice was studied by transmission electron microscopy (TEM). Special attention was directed to intercellular junctions between osteocytes, osteoblasts, and bone marrow reticular cells. These were gap junctions and adhesive devices of simple architecture referred to as primitive junctions or zonula adherens-like junctions. Gap junctions were observed between osteocytes (within the trabeculae) and osteoblasts (at the trabecular surface) and between osteoblasts and marrow reticular cells. Gap junctions were also observed between the same cell type within each of these categories. These junctions involved the plasmalemmal membranes of adjacent cell bodies and of processes. Primitive cell junctions had a similar cellular distribution. Quantitative analysis of the cell types covering or positioned around the trabecular bones and of gap junctions between these and other cells was carried out by TEM. It was found that osteoblasts were the most numerous cell type, occupying 31% of the total of each cell type positively identified around the trabeculae (31%), while pre-osteoblasts, (flattened bone marrow reticular cells) took up 26%. These data emphasise the intimate relationship of the various mesenchymal cells based on processes and intercellular junctions, and point to an anatomical and probably functional integration of trabeculae and marrow. The functional significance and putative regulatory activity of this unit are discussed.

Animals

Acute and subacute inhalation toxicity of diborane in male ICR mice.

To clarify the toxicity of diborane, we conducted acute (15 ppm for 1, 2, 4 or 8 h) and subacute (5 ppm for 2 or 4 weeks) inhalation studies on ICR mice. The concentration resulting in a 50% kill after 4 h exposure was 31.5 ppm. Body weight gain was suppressed and the lung weight was increased in diborane-exposed mice in both acute and subacute studies. In the acute study, diffuse pan bronchiolitis-like lesions developed in the lung in various degrees depending on exposure time, which can be pathologically characterized as infiltration of inflammatory cells into the terminal bronchioles and surrounding alveoli, pulmonary congestion and bleeding and/or edema. In the subacute study, we observed lymphoid hyperplasia in the perivascular and peribronchial areas, and infiltration of macrophage and plasma cells into the alveoli. In the mice exposed for 4 weeks, the lesions were more severe than in those exposed for 2 weeks, consisting of hyperplasia and desquamation of Clara cells. In the nasal cavity, we saw mucous exudate and inflammatory cells, suggesting irritation caused by diborane. The histopathological findings, except for the respiratory organs, did not reveal any exposure-related changes. No significant changes were seen in hematological and serum biochemical examinations either. In conclusion, the target organ of diborane inhalation is the respiratory organs, particularly the lung. Further inhalation experiments are essential to investigate the safety exposure levels of diborane.

Administration, Inhalation

An immunohistochemical investigation of porcine epidemic diarrhoea.

A sudden outbreak of epidemic diarrhoea of piglets occurred in Japan, the principal features being watery diarrhoea, dehydration and high mortality in newborn animals. The microscopical lesions were villous atrophy in the small intestine, the villous enterocytes being vacuolated and cuboidal in shape. The villus-crypt ratio was severely reduced, varying from 1:1 to 3:1. Transmission electron microscopy showed numerous coronaviruses within the cytoplasm of enterocytes and among microvilli. Specific antigens of porcine epidemic diarrhoea (PED) virus were detected in the cytoplasm of enterocytes by the streptavidin-biotin (SAB) technique. Infected cells, which were most abundant in the villous epithelia of the jejunum and ileum, were present in small numbers in the large intestine, the crypt epithelia, the lamina propria and Peyer's patches. The study suggests that the SAB technique is useful for the diagnosis of PED.

Animals

Surgical strategy for pheochromocytoma: emphasis on the pledge of flank extraperitoneal approach in selected patients.

BACKGROUND: Anterior transabdominal exploration has traditionally been advocated as the standard procedure for pheochromocytoma. However, some authors claim that a flank extraperitoneal approach with accurate unilateral localization is justifiable. METHODS: Retrospective analysis was performed on 87 patients with pheochromocytoma to determine the appropriateness of extraperitoneal exploration. RESULTS: There were 45 men and 42 women with a mean age of 44.7 years (range, 16 to 83 years). Fifteen patients (17.5%) had pheochromocytoma as a part of multiple endocrine neoplasia (MEN) type 2A, and four had familial pheochromocytoma, von Hippel-Lindau disease, or von Recklinghausen's disease. All tumors detected by preoperative localization studies were correctly identified and were resected through flank extraperitoneal (45 patients), transabdominal (28), thoracoabdominal (13), and posterior (1) approaches. Tumors were extraadrenal in 14, multiple in 22, bilateral in 12, and unequivocally malignant in 2 patients at the initial operation. Two patients died during the immediate postoperative period, giving an operative mortality of 2.3%. Two patients had persistent disease. During follow-up within a mean period of 5 years (range, 1 month to 13.7 years) 8 patients (9.1%) experienced recurrence or metastasis. Other than the patients with MEN 2, recurrence was not attributable to the operative approach. CONCLUSIONS: If a preoperative localization study is accurate, an extraperitoneal approach is justifiable for many patients with pheochromocytomas.

Adolescent

Dichotic listening in patients with partial section of the corpus callosum.

Patients with a complete section of the corpus callosum have been observed to exhibit strong left-ear suppression when different speech stimuli are presented to both ears simultaneously (so-called dichotic listening). Data concerning the locus of corpus callosum damage that causes strong left-ear suppression remains scanty. In the present investigation, a consonant-vowel syllable dichotic listening test was given to five right-handed patients with partial sections of the corpus callosum, which were located using MRI and accurately defined measurement procedures. The following two measurement methods were used: (i) the genu-splenium (G-S) method, in which a lesion was localized in the anteroposterior dimension relative to the total length of the corpus callosum, defined as the distance between the most anterior point of the genu to the most posterior point of the splenium; and (ii) the rostrum-splenium (R-S) method, which takes into account the curvature of the corpus callosum, and in which a lesion was localized relative to the total length of the corpus callosum, defined as the length of the curved line from the tip of the rostrum to the end of the splenium. Results were compared with scores from 50 normal control subjects. Strong left-ear suppression was observed in two patients, who had surgical sections of the posterior 15.5-18.5% of the corpus callosum as measured with the G-S method, or the posterior 20-24% of the corpus callosum as measured with the R-S method. The suppression phenomenon persisted for more than 10 years post-surgery. On the other hand, the remaining three patients, who had lesions anterior to the posterior 17-28% of the corpus callosum as measured with the G-S method or 20-33% as measured with the R-S method exhibited no left-ear extinction. Despite the common assumption that damage to the posterior part of the trunk of the corpus callosum causes strong left-ear suppression, the results from the G-S method indicated that damage to the splenium defined as the posterior one-fifth of the segment between the anterior-most and posterior-most points of the corpus callosum, cause strong left-ear suppression. By the R-S method, results showed that damage to the splenium (the posterior one-fifth of the curvature of the corpus callosum) and possibly the part extending to the most posterior part of the trunk (the posterior one-quarter of the curvature) causes strong left-ear suppression.

Adult

Immunohistological analysis of T cell functional subsets in chronic inflammatory periodontal disease.

IL-2, interferon-gamma (IFN-gamma), IL-4 and IL-6 producing T cells in periodontitis and gingivitis-affected human tissues were investigated by immunohistochemistry to clarify the relationship between T cell functional subsets and disease entity. Using alkaline-phosphatase anti-alkaline-phosphatase technique, the relative proportions of each cytokine-producing T cell were calculated in the crevicular 1/3, middle 1/3 and oral 1/3 areas selected in the connective tissue of sections. CD19:CD3 and CD4:CD8 ratios were determined on the serial sections. Compared with gingivitis tissues, the proportion of cytokine-producing cells in periodontitis-affected samples was higher overall in the crevicular 1/3 (P < 0.02). The middle 1/3 exhibited a higher percentage of cytokine-producing cells, except for IL-6-producing cells. Frequencies of cytokine-producing cells in the oral 1/3 did not differ. IL-4 was the prominent cytokine in periodontitis-affected tissues, with the highest proportion detected in the crevicular 1/3. The CD19:CD3 ratio was higher in periodontitis tissues irrespective of the location, indicating a B cell dominance in periodontitis lesions. Furthermore, a significant positive correlation between the proportion of IL-4-producing cells and the CD19:CD3 ratio was noted. The CD4:CD8 ratio consistently exceeded 2.0 in both periodontitis and gingivitis. These results suggest that immunoregulation of both periodontitis and gingivitis are T cell-dependent, but in periodontitis type 2 helper T cells predominate and thereby control B cell activation.

Adult

[Clinical efficacy of lomefloxacin (100 mg or 300 mg) single-dose therapy in female acute uncomplicated cystitis].

Female acute uncomplicated cystitis responds relatively well to antimicrobial chemotherapy. In particular, new quinolones are suited for use as antimicrobial agents in single-dose therapy of female acute uncomplicated cystitis since they have a long serum half-life and express potent antimicrobial activity against the causative microbes of this infection. Lomefloxacin (LFLX) is one such new quinolone which shows a long serum half-life, expresses potent antimicrobial activity against Escherichia coli (E. coli) and maintains an effective urinary drug concentration for approximately three days after a single administration. The authors carried out a comparative investigation of the clinical efficacy of single doses of 100 mg and 300 mg of LFLX in the treatment of female acute uncomplicated cystitis. The clinical efficacy rates with these doses, evaluated on the 3rd day after administration, were 98.2% (56/57 cases) for the 100mg-LFLX dose and 100% (62/62 cases) for the 300-mg LFLX dose. When the evaluation was performed on the 7th day after administration, the clinical efficacy rates were 91.3% (42/46 cases) for the 100-mg LFLX dose and 95.8% (46/48 cases) for the 300-mg LFLX dose. In addition, the microbial eradication rates were 73.7% (42/57 cases) for the 100-mg LFLX group and 75.8% (47/62 cases) for the 300-mg LFLX group on the 3rd day after administration, and 71.7% (33/46 cases) for the 100-mg LFLX group and 83.3% (40/48 cases) for the 300-mg LFLX group on the 7th day after administration. Although there were no statistically significant differences between the two LFLX dosage groups for these parameters at either of the evaluation times, the rates for the 300-mg LFLX dose were slightly superior. The investigators judged the efficacy of the LFLX treatment as having been insufficient in 12 patients, and urological examinations performed on six of those cases determined that there were mild underlying diseases in four cases, such as stenosis of the urethral meatus. On the basis of the findings described above, it is clear that a single 100-mg dose of LFLX provided sufficient clinical efficacy in the treatment of female acute uncomplicated cystitis, but the efficacy of the 300-mg dose of LFLX was even better. In addition, it was surmised that performance of detailed urological examinations provides an opportunity to detect mild underlying diseases that may be the cause of the intractability in female acute uncomplicated cystitis cases showing an insufficient response to treatment with antimicrobial agents such as LFLX.

Acute Disease

[Long-term monitoring of female acute uncomplicated cystitis cases after lomefloxacin single-dose therapy].

Female acute uncomplicated cystitis responds relatively well to antimicrobial chemotherapy, but this is also a disease which shows a high frequency of recurrence. However, there have been no published reports regarding long-term monitoring of the course of this disease after therapy has been administered. Accordingly, using primarily a questionnaire, the authors carried out long-term monitoring (for a mean of 242 days) of the natural course of cases of female acute uncomplicated cystitis after single-dose therapy with lomefloxacin (LFLX), a new quinolone antimicrobial agent. The subjects of this study were female patients diagnosed as having acute uncomplicated cystitis with pain upon urination, pyuria (> or = 10 WBCs/hpf) and bacteriuria (> or = 10(4) cfu/ml). LFLX was orally administered as a single dose of 100 mg or 300 mg, and the therapeutic efficacy was evaluated on the 3rd and 7th days thereafter. In principle, the evaluation of cure was performed on the 7th day after LFLX administration, and monitoring was conducted to detect early recurrence during the next 7 days (i.e., through the 14th day after treatment). Then the subjects were monitored for late recurrence during a mean follow-up period of 242 days by means of a questionnaire. Confirmation of recurrence was carried out to the greatest extent possible. It was possible to carry out long-term monitoring of the natural course of 101 cases of female acute uncomplicated cystitis in which the clinical efficacy on the 3rd day after LFLX treatment had been evaluated as good or excellent.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Stimulation by thyroid-stimulating hormone and Grave's immunoglobulin G of vascular endothelial growth factor mRNA expression in human thyroid follicles in vitro and flt mRNA expression in the rat thyroid in vivo.

To elucidate the pathogenesis of thyroid gland hypervascularity in patients with Graves' disease, we studied the expression of mRNAs for vascular endothelial growth factor (VEGF) and its receptor, Flt family, using human thyroid follicles in vitro and thiouracil-fed rats in vivo. Human thyroid follicles, cultured in the absence of endothelial cells, secreted de novo-synthesized thyroid hormone in response to thyroid-stimulating hormone (TSH) and Graves' IgG. The thyroid follicles produced VEGF mRNA but not flt-1 mRNA. The expression of VEGF mRNA was enhanced by insulin, tumor-promoting phorbol ester, calcium ionophore, dibutyryl cAMP, TSH, and Graves' IgG. When rats were fed thiouracil for 4 wk, their serum levels of TSH were increased at day 3. VEGF mRNA was also increased on day 3, accompanied by an increase in flt family (flt-1 and KDR/ flk-1) mRNA expression. These in vitro and in vivo findings suggest that VEGF is produced by thyroid follicles in response to stimulators of TSH receptors, via the protein kinase A and C pathways. VEGF, a secretable angiogenesis factor, subsequently stimulates Flt receptors on endothelial cells in a paracrine manner, leading to their proliferation and producing hypervascularity of the thyroid gland, as seen in patients with Graves' disease.

Animals

Potent thyrotropic activity of human chorionic gonadotropin variants in terms of 125I incorporation and de novo synthesized thyroid hormone release in human thyroid follicles.

Using a highly sensitive bioassay for TSH, in which human thyroid follicles incorporate 125I and release de novo synthesized thyroid hormone into the culture medium, the thyrotropic activities of various hCG preparations were studied. Under the culture conditions employed, bovine TSH (bTSH) was approximately 6- to 9-fold more active than human TSH (hTSH). Highly purified hCG prepared from urine of normal pregnant women (CR 127) had only a trivial thyrotropic activity equipotent to 0.00022 microU bTSH/U hCG or 0.0013 microU hTSH/U hCG (19.7 microU hTSH/mg hCG). Hybrid hCG (AB1ER) also elicited low thyrotropic activity (14.0 microU hTSH/mg), whereas crude hCG had moderate thyrotropic activity (0.041 hTSH microU/U hCG or 127 microU/mg protein). Deglycosylated hCG, a very weak LH/hCG receptor agonist, was the most potent agonist in thyroid follicles (588 microU hTSH/mg protein). hCGs purified from urine of patients with trophoblastic tumors had greater TSH-like activity (37-84 microU hTSH/mg protein) than purified hCG. Asialo-hCG purified from a patient with choriocarcinoma had very potent TSH-like activity (468 microU hTSH/mg). Submaximal doses of bTSH and hCG variants produced additive stimulation of thyroid function. Furthermore, the thyrotropic effect of hCG was inhibited by anti-TSH receptor antibody obtained from patients with myxedema. These in vitro findings suggest that although hCG is reported to exert potent cAMP-stimulating activity on rat thyroid-like cells (FRTL-5) and Chinese hamster ovary cells transfected with hTSH receptor complementary DNA (0.092-0.72 microU hTSH/U hCG), the thyrotropic activity induced by authentic hCG in human thyroid follicles is too weak to cause hyperthyroidism in normal pregnancy. However, hCG produced by some trophoblastic tumors, particularly asialo-hCG, has potent thyrotropic activity sufficient to cause clinically overt hyperthyroidism when produced excessively.

Animals

No-effect level of subacute tetraethoxysilane inhalation on the mouse kidney.

To determine safe exposure levels of tetraethoxysilane (TEOS) in the kidney, groups of male ICR mice (SPF grade) containing 10 animals each were exposed to TEOS, 100 ppm or 50 ppm, for 6 hours/day, 5 days/week, for 2 or 4 weeks. Tubulo-interstitial nephritis developed in mice exposed to 100 ppm for 2 and 4 weeks, but no kidney lesions or renal function changes were observed in mice exposed to 50 ppm. However, histopathological changes were detected in the nasal mucosa of mice exposed to 50 ppm TEOS. These results indicate that the occupational exposure level for TEOS should be strictly maintained below the current recommended exposure limit, 10 ppm, set by many countries and academic associations, and that renal tubular function of TEOS-exposed workers should be assessed and monitored for a long period.

Administration, Inhalation

No-observed-effect level of diborane on the respiratory organs of male mice in acute and subacute inhalation experiments.

In order to clarify the acute and subacute toxicity of diborane (B2H6, CAS: 19287-45-7) at low concentrations, male ICR mice were exposed to diborane for 1, 2, 4 or 8 h at concentrations of 1 or 5 ppm (phase I study), and for 6 h/day, 5 days/wk, over 2 or 4 wk at concentrations of 0.02 or 0.7 ppm (phase II study). Hematological and biochemical tests, and histopathological examinations of the cornea, nasal mucosa, respiratory tract and lung were carried out. All mice in both studies survived until they were sacrificed. In the phase I study, lung weight increased significantly in mice exposed to 5 ppm of diborane for 8 h. Histopathologically diffuse panbronchiolitis-like lesion was observed in mice exposed to 5 ppm of diborane for 2, 4 or 8 h. In the phase II study, slight infiltration of polymorphous neutrophil was observed mainly in the peribronchiolar region in mice exposed to 0.2 ppm or 0.7 ppm of diborane for 2 or 4 wk. In both studies, hematological and biochemical examinations failed to reveal any exposure-related changes. These results suggest that no-observed-effect level of diborane inhalation on the respiratory organs were 1 ppm in acute exposure, but 0.2 ppm of diborane inhalation for 2 or 4 wk seems to be unsafe.

Acute Disease

Melanocytes in the dark cell area of human vestibular organs.

By using surgical materials obtained from 7 cases of vestibular schwannoma, the ultrastructure of melanocytes in the dark cell area of human vestibular organs was examined by light microscopy and electron microscopy. Paraffin sections were stained with hematoxylin and eosin. Glutaraldehyde-fixed specimens were observed by electron microscopy. Melanocytes were found in the subepithelial layer of the dark cell area. Melanocytes had round or spindle-shaped nuclei and clear cytoplasm with brown pigment granules which were thought to be melanin granules. Besides melanocytes, there were fibroblasts and small blood vessels. By electron microscopy we found melanocytes with round shaped melanosomes in various stages of pigmentation, well-developed Golgi apparatus and endoplasmic reticulum in the cytoplasm, and many cytoplasmic processes. There were pinocytotic vesicles just under the limiting membrane of the melanocytes, and intermediate filaments were abundant in the cytoplasm. On the other hand long-spacing collagen was found in the connective tissue area around melanocytes.

Adult