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Biomedical subjects

Y Homma

Publications and source records attributed to Y Homma.

At least 145 records · Page 8Linked to original sources
PubMed1995

Dairy farmers have increased methacholine bronchial responsiveness independent of sensitization to mold antigens.

Patients with farmer's lung disease (FLD) and dairy farmers have nonspecific bronchial hyperresponsiveness. To examine the factors determining bronchial hyperresponsiveness among dairy farmers, we studied airway functions, airway responses to inhaled methacholine, serum total IgE levels, and antigen-specific IgE levels in 37 dairy farmers and 11 local control subjects. The 37 dairy farmers consisted of three groups; 12 farmers with episodes of FLD (FLD group), 13 farmers with serum antibody to Micropolyspora faeni (MF) and/or Thermoactinomyces vulgaris (TV) but without episodes of FLD (Ab(+) group), and 12 farmers without serum antibodies to MF and TV and without episodes of FLD (Ab(-) group). Pulmonary function tests showed small airways disorders among farmers (each of the three groups versus control subjects; p < 0.05). Methacholine provocation test, utilizing PD35Grs (a cumulative dose of methacholine that induces 35% reduction in respiratory conductance [Grs]), showed bronchial hyperresponsiveness in each group of dairy farmers compared with that in control subjects (Log PD35Grs, mean +/- SEM: 1.22 +/- 0.18, 1.00 +/- 0.17, and 1.20 +/- 0.20, respectively, versus 2.10 +/- 0.09; p < 0.001). However, there was no statistically significant difference in bronchial responsiveness among the three groups of dairy farmers. In addition, there was no significant difference in serum total IgE levels and specific IgE antibodies among the four groups. These results suggest that the bronchial hyperresponsiveness to methacholine among dairy farmers is not due to past episodes of FLD or sensitization to MF and/or TV, but is possibly due to the occupational environment of dairy farming.

Antibodies, Bacterial↗
PubMed1995

Increased susceptibility to silicosis and TNF-alpha production in C57BL/6J mice.

Toxic oxygen species and several proinflammatory cytokines are involved in the pathogenesis of silicosis. In order to understand whether factors that lead to susceptibility to ozone are also important in silicosis or not, we examined ozone-sensitive C57BL/6J mice and ozone-resistant C3H/HeJ mice as models of silicosis. We also analyzed the production of proinflammatory cytokines in both the acute and the chronic phases. On Day 2 after silica injection, the ozone-resistant C3H/HeJ mice showed significantly higher cellular responses as recognized by bronchoalveolar lavage (BAL) cell counts than did the C57BL/6J mice. In the chronic phase (Day 28 after silica injection), the ozone-sensitive C57BL/6J mice showed significantly greater responses to instilled silica judged by total protein and cell number in BAL fluid, hydroxyproline content, and histology than the ozone-resistant C3H/HeJ mice. TNF-alpha production by BAL cells after silica exposure was significantly higher in C57BL/6J mice than in C3H/HeJ mice in the chronic phase, whereas there was no significant difference in IL-1 alpha production between both strains of silica-injected mice. Also, the control C57BL/6J mice had significantly higher secretions of TNF-alpha than did the control C3H/HeJ mice in the acute phase. These results suggest that ozone-sensitive C57BL/6J mice are also more susceptible to silicosis than are ozone-resistant C3H/HeJ mice, and that the initial lower cellular responses and increase in TNF-alpha production may be related to the higher level of inflammatory and fibrotic response in the C57BL/6J mice.

Animals↗
PubMed1995

Cleavage of connectin by calpain and cathepsin D.

mu-Calpain quickly split the alpha-connectin in myofibrils into beta-connectin, and then produced a 1700-kDa component. Cathepsin D also split alpha-connectin into beta-connectin, further degrading it to fragments smaller than the 1700-kDa component with increasing incubation time. The action of cathepsin D on the connectin molecule was distinctly different from that of mu-calpain in terms of the splitting rate and manner. When freshly excised muscle was exposed to a temperature of 37 degrees C, complete disappearance of connectin (alpha, beta and 1700-kDa component) was observed within 36 h. In contrast, at 2 degrees C, about 75% of connectin was retained as beta-form even after 3 weeks. The present data suggest that the degradation of connectin in muscle might be caused by mu-calpain in the early stage of aging, and then with time, this action is replaced by m-calpain or cathepsin D. However, the possibility of other intrinsic proteases participating in the degradation of connectin still remains.

Animals↗
PubMed1995

Smoking promotes insidious and chronic farmer's lung disease, and deteriorates the clinical outcome.

Although the prevalence of serum precipitating antibodies for farmer's lung disease (FLD) is lower in smokers than in nonsmokers and FLD predominates in nonsmokers, the affects of smoking on the clinical course of the disease is not known. We compared the clinical findings and the prognosis between 12 smokers (SM-FLD) and 31 non-smokers with FLD (NS-FLD). There was no difference in age, sex, working years on farm, clinical symptoms, laboratory findings, radiographic findings, between the two groups. However, for the type of onset on the first visit for FLD, "acute single episode" type was less common, and "recurrent" and "insidious onset" types were more common in SM-FLD than in NS-FLD (8.3 vs 58.1, 91.7 vs 41.9%, respectively, p < 0.05). Although working status and mask wearing status were not significantly different between the two groups after the diagnosis of FLD, patients with symptoms and/or radiographic abnormalities of FLD of more than 6 months were found more frequently in SM-FLD than in NS-FLD (66.7 vs 19.4%, p < 0.005). And also SM-FLD had more recurrences of FLD than NS-FLD after the initial diagnosis of FLD (1.58 +/- 1.56 vs 0.47 +/- 1.07, p < 0.05). SM-FLD tended to have lower % VC than NS-FLD (73.6 +/- 7.4 vs 88.5 +/- 3.9%, respectively, p = 0.06). Regarding the prognosis, the 10-year survival rates were 70.7% in SM-FLD, and 91.5% in NS-FLD (p < 0.05). These results suggest that smoking may make FLD insidious and chronic, and deteriorates the clinical outcome.

Adolescent↗
PubMed1995

Fastigiofugal projection to the brainstem nuclei in the cat: an anterograde PHA-L tracing study.

Fastigial projections to brainstem nuclei were studied using an anterograde neural tracer, Phaseolus vulgaris leucoagglutinin (PHA-L). Microinjections of PHA-L were made into the rostral pole, and middle and caudal parts of the left fastigial nucleus in cat. In addition to fastigioreticular and fastigiovestibular projections, fastigiofugal projections to cranial motor nuclei (IV, VI and VII) and those nuclei involved in autonomic control were identified. At the medullary level, a topographic arrangement of fastigioreticular projection was observed. Rostral and caudal parts of the fastigial nucleus projected to the ventral and dorsal parts of the medial reticular formation, respectively. Fastigiofugal fibers which originated from the rostral part of the fastigial nucleus innervated heavily the nucleus reticularis gigantocellularis (NRGc), nucleus reticularis magnocellularis (NRMc) and the ventral paramedian reticular nucleus (PRN). Those fibers from the middle part innervated heavily the ventrolateral vestibular nucleus (VLV), NRGc, NRMc, ventral and dorsal PRN and parasolitary tract nucleus. From the caudal part of the fastigial nucleus, projections to the cranial motor nuclei (IV, VI and VII), VLV and inferior vestibular nucleus were observed.

Animals↗
PubMed1995

[Role of viral infections in acute exacerbation of idiopathic interstitial pneumonia].

To evaluate the possibility that viral infections can trigger acute exacerbations of idiopathic interstitial pneumonia (IIP), we analyzed data from 105 patients with IIP. Acute exacerbation was defined as an increase in dyspnea, a decrease in PaO2 by more than 10 Torr, and worsening of chest radiographic findings within one month. Viral infection was said to be involved when patients had more than a 4-fold change in viral antibody titer or viral inclusion bodies in sputum during the acute exacerbation. Of the 105 patients with IIP, 30 had acute exacerbations. Among these 30 patients, viral infection was said to be involved in 11 (37%). Presumptive viruses were influenza virus (n = 6), parainfluenza virus (n = 1), herpes simplex virus (n = 1), RS virus (n = 1), and cytomegalovirus (n = 2). The levels of serum immunoglobulin A (IgA) before acute exacerbations were significantly lower (p < 0.05) in patients in whom viral infection was said to be involved. These results suggest that viral infection associated with a low value of serum IgA is an important trigger of acute exacerbations of IIP.

Aged↗
PubMed1995

[Acyclovir and guinea-pig airway smooth muscle].

Acyclovir, an anti-herpes virus drug, has been reported to affect aspirin-induced asthma (AIA). Acyclovir was reported to decrease the sensitivity to aspirin in some AIA patients. Although the hypothesis that AIA is related to viral infection has been stated, there is no proof that patients with AIA are infected with a specific virus. Therefore, whether the effect of acyclovir on AIA is due to an antiviral effect is not clear. We hypothesized that acyclovir directly affects airway smooth muscle. To test this hypothesis, we examined whether acyclovir can directly contract or relax guinea-pig airway strips, and whether it can modify contraction or relaxation induced with several agents in vitro. Acyclovir did not directly affect basal smooth muscle tone and did not affect the responses to leukotriene D4, prostaglandin E2, carbachol, or KCl. We conclude that acyclovir has no direct effect on the function of guinea-pig airway smooth muscle.

Acyclovir↗
PubMed1995

Maximum flow rate--the single uroflowmetric parameter in clinical trials for benign prostatic hyperplasia?

BACKGROUND: Uroflowmetry parameters should be examined for both reliability and optimal test conditions in patients with benign prostatic hyperplasia (BPH), since the difference between one pre- and one post-intervention uroflow rate is usually evaluated in clinical trials of BPH. PATIENTS AND METHODS: Reproducibility of maximum flow rate (Qmax) or its modified forms, and the effects of urinary volume on the reproducibility were examined in terms of Spearman's correlation coefficient (r) in 67 BPH patients. RESULTS: Qmax had a higher r (0.672) as compared to other uroflow rates, such as mathematically modified forms of Qmax and adjusted values of Qmax on nomograms. Reliability was improved by bladder instillation (r = 0.811) or when voided volume was > or = 150 ml or the ratio of volumes was < 2.0 (r = 0.690-0.736). CONCLUSION(S): Qmax, preferably performed with urinary volumes of more than 150 ml or the ratio of volumes less than 2.0, is the most practical single parameter at present in the comparison of two uroflowmetric tests in BPH treatment.

Aged↗
PubMed1995

Neuroanatomical and neurophysiological bases of postural control.

At this stage of our study, we do not know yet the relative contribution of each pathway that descends from the cerebral cortex, the cerebellar nuclei, and the SN to the control of pontomedullary reticuloreticular and reticulospinal neurons. Nor do we know the resultant activation patterns of reticulospinal neurons and those of axial and proximal motoneurons in relation to postural fixation and equilibrium. In dealing with the physiology of posture, such as the maintenance or change of body position, we are dealing with the emergent properties of the total system that are not described by the sum of the properties of its parts. Learning how a system subcomponent behaves in a carefully defined and constrained set of circumstances gives us no guarantee that the subcomponent will behave according to the same rules if the circumstances were changed (59). Further behavioral studies in animal and human subjects, especially using natural posture and movements, plus studies aimed at elucidating the fine architecture of the target system, including identification of acting neurotransmitters at each synaptic level of a system subcomponent, are now needed to confirm existing hypotheses (10, 37, 47) and elaborate new ones related to the control of posture and movement.

Animals↗
PubMed1994

Bidirectional regulation of c-fos promoter by an oncogenic gip2 mutant of G alpha i2. A novel implication of retinoblastoma gene product.

G alpha i2 is a tissue-specific proto-oncogene product, whose activated mutant gip2 induces transformation through less defined downstream pathways. We found that c-fos promoter is a target of gip2 in multiple kinds of cells. Serum response element was shown to be the positive enhancer element that mediates gip2-induced c-fos expression. We further demonstrated that gip2 stimulates the negative silencer activity of the retinoblastoma (Rb) control element (RCE) and inhibits the c-fos promoter activity through RCE located in the c-fos promoter region. The effect of gip2 on RCE was shown to be mediated by the Rb gene product (pRb). Furthermore, gip2 augmented underphosphorylated active form of pRb by promoting pRb expression and by affecting the phosphorylation state of pRb. gip2 therefore propagates both positive and negative signals to the c-fos promoter through two different elements, and pRb mediates the negative signal of gip2. We conclude that gip2 has bifunctional roles in transformation which pRb critically regulates. Given that Rat-1 cells, which gip2 can transform, lack the sensitivity to the gip2/pRb-mediated negative pathway, this study provides a novel insight into oncogenesis by gip2 and its tissue specificity.

Animals↗
PubMed1994

Promotional effect of two-generation exposure to a high-fat diet on prostate carcinogenesis in ACI/Seg rats.

Epidemiological studies have shown an association between a high-fat diet and a high mortality rate from breast, colon, and prostate cancer. However, the promotional effect of a high-fat diet on experimental carcinogenesis has not been fully established for the prostate. In this study, the effect on prostatic carcinogenesis of two-generation exposure to a high-fat diet was investigated using ACI/Seg rats, a strain with high incidence of spontaneous prostate cancer. A high-fat diet (20% corn oil) or a low-fat diet (5% corn oil) was given to mother rats during pregnancy and the newborn male rats were fed the same diets for 60 or 100 weeks after weaning. At 100 weeks, atypical hyperplasia and adenocarcinoma of the prostate were respectively found in 73.3% (11/15) and 20.0% (3/15) of the high-fat diet group and in 20.0% (3/15) and 0% (0/15) of the low-fat diet group. There was a significant increase of atypical hyperplasia in the high-fat diet group (P < 0.05). The serum concentrations of sex hormones and the prostatic proliferative activity as measured by flow cytometry or bromodeoxyuridine labeling were not significantly affected by diet. These results showed that feeding a high-fat diet before conception and from the beginning of organogenesis had a marked promotional effect on the early stage of prostate carcinogenesis in rats.

Animals↗
PubMed1994

Evidence for the accumulation of oxidative stress during cellular ageing of human diploid fibroblasts.

We have examined the level of 8-hydroxydeoxyguanosine (8-OH-dG) in the DNA of human diploid fibroblast TIG-1 cells at various stages of cellular ageing. Cellular DNA was obtained from cell lysates by simple precipitation with ethanol and analyzed 8-OH-dG levels by an electrochemical detection system. The data reveals that this method is valid for the detection of 8-OH-dG at levels of 1 x 10(-6) 8-OH-dG/dG without altering the recovery of other deoxynucleosides. Using this method, we demonstrate a significant increase in 8-OH-dG content during cellular ageing up to a 50 population doubling level (PDL) of TIG-1 cells, with levels of 0.5 x 10(-6) and 1.6 x 10(-6) 8-OH-dG/dG in young (22 PDL) and old (50 PDL) cells, respectively. The level decreases with further ageing and is 1.3 x 10(-6) 8-OH-dG/dG in senescent cells. We also show that the repair activity for the 8-OH-dG lesion declines significantly during cellular ageing, a phenomenon that might be associated with the increase in 8-OH-dG levels.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

Drosophila phospholipase C-gamma expressed predominantly in blastoderm cells at cellularization and in endodermal cells during later embryonic stages.

A Drosophila gene encoding a gamma-type isozyme of phosphoinositide-specific phospholipase C (PLC) was isolated and characterized. The gene, termed plc-gamma d, was mapped at position 14B-C of the X chromosome. The encoded protein, termed PLC-gamma D, contains X and Y regions, common to all known PLC isozymes. The two regions are split by a Z region that comprises two src homology 2 and one src homology 3 domains and is characteristic of gamma-type mammalian PLC (PLC-gamma 1 and -gamma 2). The deduced amino acid sequence of PLC-gamma D shows overall similarity to mammalian PLC-gamma s; no large deletion was observed except the short C-terminal extended region. In particular, the two split catalytic domains (X and Y regions) and the regulatory Z region including the src homology 2 and src homology 3 domains are well conserved. The mRNA is expressed throughout development, but expression is relatively higher during the embryonic stage, suggesting fundamental and important roles in both cell proliferation and differentiation. Distribution of the mRNA during embryogenesis, as analyzed by whole amount in situ hybridization, revealed that the mRNA emerges and reaches maximum levels at the cellular blastoderm stage and then decreases rapidly to a lower level. In later embryonic stages, invaginated anterior and posterior midgut primordia show high levels of mRNA expression, and fused midgut also maintains a high level of expression. In other tissues and cells, the mRNA was detected at lower levels. These results indicate that Drosophila PLC-gamma may be involved in universal cellular processes mediated possibly by receptor tyrosine kinases during embryogenesis and may also play specific roles during cellularization and midgut differentiation.

Amino Acid Sequence↗
PubMed1994

Purification and characterization of nuclear phospholipase C specific for phosphoinositides.

A phosphoinositide-specific phospholipase C (PLC) was solubilized from the isolated nuclei of rat ascites hepatoma AH7974 cells by ultrasonication in 2 M KCl. The extract was then subjected to five steps of column chromatographies in the order of Sephacryl S-300, phosphocellulose, Mono Q, Mono S, and Superose 6. Four forms of PLC (tentatively designated as N1, N2, N3, and N4) were purified 440-1400-fold. N1, N2, N3, and N4 showed apparent molecular masses of 85, 83, 80, and 88 kDa, respectively, on SDS-polyacrylamide gel electrophoresis. N1 cross-reacted with the antibody against the delta 1 isoform, while the other three forms did not cross-react with any of the antibodies against PLC-delta 1, -gamma 1, -gamma 2, and -beta 1. They hydrolyzed phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP), and phosphatidylinositol 4,5-bisphosphate (PIP2) but did not show any activities against phosphatidylcholine and phosphatidylethanolamine. They showed the same optimal pH:pH 6.5 for PI hydrolysis and pH 7.0 for both PIP and PIP2 hydrolyses. They absolutely required Ca2+ for activity, with optimal concentrations of 10(-3)-10(-5) M for PIP and 10(-4)-10(-5) M for PIP2. For PI hydrolysis, N1, N2, and N3 required a Ca2+ concentration higher than 10(-2) M whereas N4 revealed significant activity even at 10(-5) M Ca2+ concentrations. Two forms of plasma membrane PLC and three forms of cytosolic PLC were purified from AH7974 cells by the same procedure as for nuclear PLC. Comparative study with these three groups revealed that all of the purified PLC isoforms shared similar enzymological properties except N4, which showed an exceptionally high affinity to Mono S column and was active at low concentrations of Ca2+ for PI as substrate. Furthermore, when PLC isoforms of nuclei from adult resting rat liver were compared with those from regenerating rat liver after partial hepatectomy, a PLC isoform corresponding to N4 of AH7974 cells was found only in regenerating liver nuclei. From these results, it was suggested that the nuclei of growing liver cells possessed a unique form of PLC (N4).

Animals↗
PubMed1994

Tyrosine kinases Lyn and Syk regulate B cell receptor-coupled Ca2+ mobilization through distinct pathways.

Stimulation of B lymphocytes through their antigen receptor (BCR) results in rapid increases in tyrosine phosphorylation on a number of proteins and induces both an increase of phosphatidylinositol and mobilization of cytoplasmic free calcium. The BCR associates with two classes of tyrosine kinase: Src-family kinase (Lyn, Fyn, Blk or Lck) and Syk kinase. To dissect the functional roles of these two types of kinase in BCR signaling, lyn-negative and syk-negative B cell lines were established. Syk-deficient B cells abolished the tyrosine phosphorylation of phospholipase C-gamma 2, resulting in the loss of both inositol 1,4,5-trisphosphate (IP3) generation and calcium mobilization upon receptor stimulation. Crosslinking of BCR on Lyn-deficient cells evoked a delayed and slow Ca2+ mobilization, despite the normal kinetics of IP3 turnover. These results demonstrate that Syk mediates IP3 generation, whereas Lyn regulates Ca2+ mobilization through a process independent of IP3 generation.

Animals↗
PubMed1994

Enhanced phosphoinositide metabolism in colorectal carcinoma cells derived from familial adenomatous polyposis patients.

The production of the second messenger molecules diacylglycerol and inositol 1,4,5-trisphosphate is mediated by activated phosphatidylinositol-specific phospholipase C (PLC) enzymes. We report the enhancement of the phosphoinositide metabolism pathway in KMS-4 and KMS-8 cells, both of which are human colorectal carcinoma cell lines derived from familial adenomatous polyposis patients. In these cells, the cellular contents of diacylglycerol and inositol 1,4,5-trisphosphate were constitutively increased and the PLC activity in vitro was significantly high, as compared with those in normal colon cells or in other sporadic colorectal carcinoma cells. Northern and Western analyses showed the high expression levels of both PLC-gamma 1 and PLC-delta 1 in KMS-4 and KMS-8 cells. Moreover, we detected the enhancement of protein-tyrosine kinase activity and tyrosine phosphorylation of PLC-gamma 1 in these KMS cells. These results suggest the involvement of activated phosphoinositide signaling pathways in the colorectal tumorigenesis of familial adenomatous polyposis.

Adenocarcinoma↗