Search PubMedSearch

Biomedical subjects

H Tada

Publications and source records attributed to H Tada.

At least 19 recordsLinked to original sources

Induction and repair of UVB-induced cyclobutane pyrimidine dimers and (6-4) photoproducts in organ-cultured normal human skin.

To examine the induction and repair of UV-induced DNA damage, indirect immunofluorescence was performed on UVB-irradiated organ-cultured normal human skin using monoclonal antibodies specific for either cyclobutane pyrimidine dimers or (6-4) photoproducts. Nuclear immunofluorescence of cyclobutane pyrimidine dimers and (6-4) photoproducts were observed in a dose-dependent manner after UVB irradiation. The intensity of nuclear immunofluorescence of the upper epidermal layers was stronger and clearer than that of the lower epidermal layers. DNA repair time-course studies showed that both types of DNA damage could be repaired within 24 h after UVB irradiation.

Cyclobutanes

The effect of recombinant human interleukin-5 on eosinophil accumulation and degranulation in human nasal mucosa.

Recombinant human interleukin-5 (rhIL-5) was administered repeatedly onto the nasal mucosa of individuals with Japanese cedar pollinosis outside the pollen season. The numbers of eosinophils and epithelial cells and the amount of eosinophil cationic protein (ECP), secretory IgA (S-IgA), and IgA in the nasal lavage fluid increased significantly after the application of rhIL-5. Responsiveness to histamine was also enhanced after the application. When S-IgA was administered onto the nasal mucosa after application of rhIL-5, the amount of ECP in the nasal lavage fluid was significantly more increased. The above findings together with the facts that IL-5 promotes production of IgA, that IgA receptors are present on eosinophils, and that rhIL-5 does not increase release of ECP from eosinophils isolated from the peripheral blood suggest that a series of possible reactions consisting of (1) IL-5--induced production of IgA from the immune-mediating cells, (2) binding of secretory components released from either serous glandular cells or epithelial cells of the nasal mucosa with IgA, (3) release of ECP from eosinophils induced by S-IgA and/or IgA, (4) epithelial damage to the nasal mucosa, and (5) development of nasal hyperreactivity to histamine.

Adult

Effects of probucol on impaired cardiac performance and lipid metabolism in streptozotocin-induced diabetic rats.

Plasma lipids and cardiac performance were studied in diabetic rats treated with probucol. Male Wistar rats were rendered diabetic with a single intraperitoneal injection of streptozotocin (STZ, 75 mg/kg). Nondiabetic control rats received the vehicle alone. Two weeks after STZ or vehicle injection, control and diabetic rats were randomly assigned to probucol-treated or untreated groups. The rats in the two probucol-treated groups (control- and diabetic-probucol groups) were fed a diet containing 1% probucol (w/w) for 4 weeks. Blood was drawn, and then cardiac performance was assessed by the isolated perfused working heart technique. Probucol treatment had no effect on the cardiac performance of the nondiabetic control rats. The peak left ventricular developed pressure and maximum rate of change in left ventricular pressure during systole were significantly greater in the probucol-treated diabetic rats than in the untreated diabetic rats (p less than 0.05), although cardiac performance did not improve to the level in the nondiabetic rats. Plasma cholesterol, free fatty acid, and phospholipid were significantly elevated in the untreated diabetic rats, and probucol treatment decreased significantly the plasma cholesterol and free fatty acid concentrations (p less than 0.05). These data suggest that probucol treatment improves plasma lipids and cardiac performance in rats with experimental diabetes and may prevent diabetic cardiomyopathy.

Animals

Induction of the 72-kD heat shock protein in organ-cultured normal human skin.

To study the induction of heat shock protein (HSP) of normal human skin, the indirect immunofluorescence method, using monoclonal antibody directed against 72-kD HSP, was applied in organ-cultured normal human skin that was treated with heat, UV, or chemicals. The present study provided new evidence that HSP 72 was induced not only by heat and chemical agents, such as L-azetidine 2-carboxylic acid, and sodium arsenite, but also by ultraviolet (UV B and C). The result suggests that normal human skin has an induced protective function against numerous environmental stresses.

Arsenic

Induction of the 72-kD heat shock protein in xeroderma pigmentosum complementation group A fibroblasts.

In mammalian cells, 72-kD heat shock protein (HSP72) is the major stress-inducible protein that is thought to play a protective role against the various environmental stresses. In order to know the induction mechanism of HSP72, we examined the HSP72 in DNA repair-deficient xeroderma pigmentosum group A fibroblasts (XP2OSSV) and normal fibroblasts (WI38VA13) by the indirect immunofluorescence method using a monoclonal antibody specific for the inducible 72-kD protein. Heat-shock treatment of the same survival fraction (5% survival) induced HSP72 in xeroderma pigmentosum (XP) and normal cells. However, as compared with XP cells, normal cells showed the induction of HSP72 more rapidly and strongly. When XP and normal cells were irradiated with UVC at the same survival dose (10% survival), apparent induction of HSP72 was observed in both cell lines. In the case of UVC irradiation at the same dose (1.0 J/m2), though XP cells showed the induction of HSP72, HSP72 was not induced in normal cells. In both cell lines, heat-shock treatment caused more rapid induction of HSP72 than UV irradiation. These results suggest that the induction mechanism of HSP72 might be different between heat-shock treatment and UV irradiation. In addition, in the case of UV irradiation, the extent of DNA damage after DNA repair or the cell death might be involved in the induction of HSP72.

Cell Line, Transformed

Separate isolation of Clostridium difficile spores and vegetative cells from the feces of newborn infants.

A modified taurocholate-cefoxitin-cycloserine-fructose agar medium, pH 5.5, on which vegetative cells alone could grow, was newly devised for separate isolation of Clostridium difficile vegetative cells and spores from feces. The ratio of C. difficile-positive feces from healthy newborn infants younger than 10 days of the age was 30.8%, and 93.3% of feces from healthy infants older than 20 days were positive for C. difficile. C. difficile spores alone were detected in twenty-one samples (75%) of C. difficile-positive Twenty-eight specimens. Only 10.7% (3/28) C. difficile vegetative cells alone were detected. C. difficile spores alone were detected in one of nine healthy adults. These collective results offer potential explanations for high frequent isolations of C. difficile from newborn infants without occurrence of pseudomembranous colitis.

Bottle Feeding

Prevention of perinatal transmission of hepatitis B virus carrier state.

By means of passive and active immunization with hepatitis B immunoglobulin and hepatitis B vaccine, 396 of 407 babies born to hepatitis B antigen-positive carrier mothers, were protected from establishing the hepatitis B virus (HBV) carrier state during a follow-up period of 12 months or longer. Four infants developed the HBV carrier state before the completion of the immunoprophylaxis schedule, and another seven developed the state after the completion of the schedule. Seroconversion of anti-HBc was observed in 26.8% of the successfully protected infants. In Japan a nationwide program to prevent the vertical transmission of HBV with these procedures was established in 1986, and so liver diseases due to HBV are expected to be eliminated in the near future.

Carrier State

[Detection of verotoxin-producing Escherichia coli using polymerase chain reaction from dairy cattle].

The vero cytotoxin (VT) is responsible for hemorrhagic colitis and hemolytic uremic syndrome. Polymerase chain reaction (PCR) was used to detect VT-producing coliform bacteria from dairy cattle. It was found that 39 (33.3%) of the 117 fecal samples examined were recognized with VT genes in BGLB enrichment broth by the PCR method (named BGLB-PCR). Of the VT-positive samples, 31 samples (26.5%) were found to have VT-producing Escherichia coli. Frequencies of isolation in younger cattle (under 5 months) were 31.3-32.9%. On the other hand, the PCR method using the bacterial suspension of some colonies from DHL selective isolation medium (named DHL-PCR), was used for 105 samples. The DHL-PCR was validated according to the number of colonies tested for detecting VTEC. When using E. coli strains which have been stored after isolation by the conventional culture method, the VT-producing strains found were 7 (10.3%) of the 68 isolates tested. The 101 out of the 108 VTEC strains from cattle were classified into 14 O groups. 4 O serogroups (O26, O111, O145, O157) from 60% of VTEC positive cattle, were also the most common in humans with diarrhea. All E. coli O157:H7 isolates failed to ferment after 48 hrs and to hydrolyze 4-methyl-umbelliferyl-beta-D-glucuronide (MUG). These results suggests that cattle may play an important role in human VTEC infections. The BGL B-PCR technique is usefull in ecological studies for VT-producing pathogens.

Animals

A novel sequence-specific DNA-binding protein, LCP-1, interacts with single-stranded DNA and differentially regulates early gene expression of the human neurotropic JC virus.

We have identified a novel brain-derived single-stranded-DNA-binding protein that interacts with a region of the human neurotropic JC virus enhancer designated the lytic control element (LCE). This nuclear factor, LCP-1 (for lytic control element-binding protein 1), specifically recognizes the LCE, as determined by gel retardation assays. Alkylation interference showed that specific nucleotides within the LCE were contacted by LCP-1. Subsequent experiments revealed that point mutations within the LCE differentially affected LCP-1 binding. UV cross-linking and competition analysis suggested that the LCP-1 DNA-protein complexes were 50 to 52 and 100 to 120 kDa in size. Promoter mutations that affected LCP-1 binding reduced early mRNA transcription during the early phase of the lytic cycle. However, upon DNA replication in the presence of JC virus T antigen, when early mRNA initiation shifts to new locations indicative of the late phase, the LCP-1 mutations had no effect. We suggest that the JC virus early transcription unit is differentially regulated by LCP-1 prior to but not after DNA replication, suggesting a novel mechanism by which DNA structure regulates eukaryotic gene expression.

Base Sequence

Interleukin 2 and tumor necrosis factor alpha are complementary for proliferation of the hematopoietic stem cell line LyD9.

We have shown that tumor necrosis factor alpha (TNF alpha) and interleukin 2 (IL-2) are complementary for stimulation of growth of the hematopoietic stem cell line, LyD9. Neither TNF alpha nor IL-2 alone could stimulate the proliferation of LyD9 cells even after pre-incubation with these growth factors. The number of high-affinity IL-2 receptors on LyD9 cells did not increase after incubation with IL-2 and TNF alpha. These results suggest that the proliferative response of LyD9 by TNF alpha and IL-2 is not mediated by receptor inducing activities. We used the induction of the proto-oncogenes c-myc and c-pim to characterize the proliferative stimulation by IL-2 and TNF alpha. Northern blot analysis revealed that the simultaneous addition of IL-2 and TNF alpha was more efficient than IL-2 alone for c-myc mRNA induction. However, the addition of TNF alpha and IL-2 could not increase c-pim mRNA more than the level induced by IL-2 alone. The results indicate that the two growth factors complement each other by transducing different types of growth signal.

Blotting, Northern

[Epidemiological analysis of infectious mononucleosis as primary Epstein-Barr virus infection].

We report the characteristics of 45 Epstein-Barr virus (EBV)-infected patients visiting our hospital from 1989 to 1991 in comparison with 102 patients seen from 1981 to 1988. Cases of infectious mononucleosis (IM) increased especially in patients over 30 years old. They tended to have nonspecific symptoms and signs for IM such as general fatigue. Immunologically showed twice higher positivity for anti-EBV VCA-IgM antibody in the recent 3 years when compared to the previous 8 years. The patients with anti-EBNA antibody decreased in the recent 3 years. This may be due to early diagnosis as IM. EBV also causes atypical diseases. non-IM in this report, including hematological or neurological disorders. We indicated here the increased number and advanced age of patients with IM and early diagnosis as IM in the recent 3 years compared to the previous 8 years.

Adolescent

[N-isopropyl-p-[I123] iodoamphetamine single photon emission computed tomography (I123-IMP SPECT) and child neurology].

We studied the clinical usefulness of I123-IMP SPECT in 50 pediatric patients with CNS disorders, which were categorized into the convulsive disorder group (n = 20), the cerebrovascular disorder group (n = 10), the acute encephalopathy or CNS infection group (n = 10), the metabolic or degenerative disorder group (n = 6), the congenital abnormality group (n = 2) and the migraine group (n = 2). The findings obtained were compared with those of cranial CT. I123-IMP SPECT revealed abnormal findings in 45 out of the 50 patients (90%), although cranial CT showed abnormal findings in only 24 patients (48%). This difference was statistically significant (p less than 0.01). In all groups except the migraine, we could find abnormal findings in more than 90% of the patients. Out of 28 patients without focal findings on the initial CT scanning, I123-IMP SPECT showed focal abnormalities in 26 patients (93%). Moreover in many patients with focal neurological abnormalities, we found focal abnormalities of I123-IMP SPECT related with neurological abnormalities of the patients. From these findings, we think I123-IMP SPECT might be better to CT scanning in examining a localized lesion. It was found that in many patients with focal abnormalities in CT scanning, I123-IMP SPECT showed larger abnormalities in CT scanning. By using I123-IMP SPECT we might be able to study the blood perfusional state surrounding the abnormal area shown by CT. In 3 patients with acute cerebrovascular disorders, I123-IMP SPECT revealed abnormal findings 3 to 11 days earlier than cranial CT.I123-IMP SPECT might be useful for early recognition of the pathological state.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors

31P-nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in patients with chronic lung disease and congestive heart failure.

The development of 31P-nuclear magnetic resonance (NMR) has enabled direct and non-invasive measurements of muscle metabolism. Serial measurements of the phosphocreatine/inorganic phosphate (PCr/Pi) ratio, which is closely related to the adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio and pH during and after forearm exercise were performed in 11 patients with chronic lung disease (CLD), nine patients with chronic heart failure (CHF) and eight control subjects. As compared with control subjects, the PCr/Pi ratio in the patients with CLD or CHF was lower during the recovery period and significantly lower at three and 4 min exercise. The pH values after exercise were lower in patients with CLD or CHF compared to control subjects. The PCr/Pi ratio at 4 min after exercise in the patients with CLD or CHF did not correlate with parameters of cardiac function or arterial and mixed venous oxygen tension. The arterial oxygen content and output in patients with CLD and CHF were significantly lower than that of control subjects. Nutritional parameters were not statistically different among the three groups. These observations suggest that metabolic abnormalities may be present in the skeletal muscles of patients with CLD and CHF that are not due to under-nutrition. These may result from reduced arterial oxygen output and, partially, from physical detraining.

Aged

[Effect of coix seed on the changes in peripheral lymphocyte subsets].

Coix seed has been used in patients with verruca vulgaris and verruca planae juveniles, which have been considered to be induced by viral infection. Moreover, coixenolide, component in the seeds of coix, was reported to show anti-tumor activity. Possibly coix seed may have some influence on the cytotoxic activity of peripheral lymphocytes but there has been no data on this. Then we investigated the changes in number of cytotoxic lymphoid cells in seven volunteers before, during (four weeks) and after taking six coix seed tablets. Lymphocyte subsets were analyzed with monoclonal antibodies using a flow cytometer. The level of CD3+CD56+ (MHC-non restricted cytotoxic T cells) markedly increased at four weeks (before 1.9 +/- 0.5% vs four weeks 4.2 +/- 0.7%, p less than 0.01). The level of CD16+CD57- (the mature, most active natural killer cells) increased at three weeks (before 4.5 +/- 0.8% vs three weeks 5.2 +/- 0.8%, p less than 0.05). The level of CD3-CD56+ (natural killer cells) and the level of CD16+CD57+ (the variable active natural killer cells) decreased at one week and returned to normal level thereafter (before 13.7 +/- 2.1% vs one week 11.2 +/- 1.5%, p less than 0.05; before 8.8 +/- 1.5% vs one week 6.9 +/- 1.3%, p less than 0.05, respectively). These results indicate that coix seed modulate the peripheral blood lymphocyte subsets and may be effective to virus disease through the enhancement of cytotoxic activity.

Drugs, Chinese Herbal

Biochemical evidence for a third chain of the interleukin-2 receptor.

Two receptor proteins that specifically bind interleukin-2 (IL-2) have been identified previously. The L (Tac or alpha) chain can bind IL-2 with a Kd value of 10 nM (low affinity). Although the H (beta) chain expressed on lymphocytes can bind IL-2 with a Kd value of 1 nM (intermediate affinity), transfected fibroblasts expressing the H chain cannot bind IL-2, suggesting the involvement of other lymphocyte-specific factors for the function of the H chain. To obtain direct evidence for the presence of a third component of the IL-2 receptor, we examined the IL-2 binding activity of detergent-solubilized cell membrane preparations. We found that lysates of transfected Cos7 cells expressing H chains can bind IL-2 when mixed with lysates from lymphocytes that cannot bind IL-2. Chemical cross-linking of 125I-IL-2-bound lysate mixture and subsequent immunoprecipitation with a noncompetitive anti-H chain antibody gave rise to two 125I-IL-2-bound proteins, a 56-kDa protein (p56) and the H chain, although neither the H chain nor p56 alone is able to bind IL-2. These results indicate that p56 is the IL-2 receptor third chain that is required for IL-2 binding to the H chain. A similar lysate mixing experiment also showed that p56 is involved in IL-2 binding to the high affinity IL-2 receptor by forming the quaternary complex of IL-2, p56, L chain, and H chain.

Animals

Pravastatin, a HMG-CoA reductase inhibitor, blocks the cell cycle progression but not Ca2+ influx induced by IGF-I in FRTL-5 cells.

IGF-I, when added to the TSH-primed FRTL-5 cells, induces a long lasting Ca2+ influx, and then, DNA synthesis. Moreover, Ca2+ channel agonist, B AY K8644 can mimic these effects on cell proliferation. We studied the effect of HMG-CoA reductase inhibitor, Pravastatin on IGF-I-induced cell cycle progression in FRTL-5 cells. Pravastatin inhibited DNA synthesis induced both by IGF-I and by BAY K8644. In contrast, Ca2+ influx stimulated by IGF-I was unaffected. These data demonstrate that the signal transduction pathway evoked by IGF-I may possibly involve pravastatin-sensitive process at the downstream step of Ca2+ entry. HMG-CoA reductase inhibitors are known to modulate some cellular signal transduction systems by blocking the membrane attachment of low molecular weight GTP binding proteins such as p21ras. Therefore, pravastatin-sensitive process that we have shown here might possibly involve some of such small G protein.

Animals

Experimental study of neurotization of denervated muscles with nerve-to-vein transfer.

Neurotization of denervated muscles was attempted by means of coaptation of peripheral nerves to the veins draining these muscles. In Sprague-Dawley rats, the lateral gastrocnemius branch from the tibial nerve was severed and its proximal end was sutured to the distal stump of the lateral gastrocnemius vein. In all animals nerve-muscle communication was confirmed electrophysiologically 2 and 6 months after the operation. However, histological examination revealed that the regenerated nerve fibers were not within the vessel lumen, but ran through the scar tissue in close proximity to the outside of the vessel, to enter the muscle. Control animals, in which only nerve resection was done, did not display nerve reinnervation. These results suggest that, although nerve fibers did not regenerate into the vein, the vein works well as a guide for regenerating nerve fibers to denervated muscle.

Animals

Regulation of JCVL promoter function: evidence that a pentanucleotide "silencer" repeat sequence AGGGAAGGGA down-regulates transcription of the JC virus late promoter.

The human neurotropic papovavirus JCV contains sequences within the two 98-bp tandem repeats which play a key role in glial-specific transcription of the viral early and late promoters. Previous analysis of the 98-bp sequence has delineated several protein-binding domains that are recognized by nuclear factors present in human brain cells. In the present study, by deletion mutation analysis, we have identified a region within each 98-bp repeat that reduces transcriptional activity of the JCV late promoter (JCVL). Using synthetic oligonucleotides spanning this region, designated "OP," we demonstrate that down-regulation of the JCVL promoter is associated with a pentanucleotide repeat sequence (AGGGAAGGGA) juxtaposed to the poly(dA) tract within the 98-bp tandem repeats. The OP sequence interacts specifically with a protein derived from glial nuclear extract and forms a major 56- to 60-kDa complex. Methylation interference experiment indicates that the three G residues proximal to the poly(dA) tract make major groove contacts with the protein. Single-base-pair substitution of these residues suggests that the complex can form in the presence of two of the three guanosyl residues. The possible role of this protein in regulating the JCV lytic cycle in concert with nearby regulatory elements within JCV promoter region is discussed.

Animals