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Biomedical subjects

K Iwai

Publications and source records attributed to K Iwai.

At least 127 records · Page 7Linked to original sources
PubMed1994

Idiopathic pulmonary fibrosis. Epidemiologic approaches to occupational exposure.

Idiopathic pulmonary fibrosis (IPF) risk-related factors were epidemiologically investigated on the basis of 1,311 Japanese IPF autopsy cases selected from the annual complications of autopsy data records in Japan during a 12-yr period. Age and sex distribution of the subjects revealed a high peak in their seventh decade with males predominating. The IPF rate was more than two times higher (p < 0.01) among subjects engaged in occupations that exposed them to dust or organic solvents compared with those in other jobs. To ascertain job characteristics, an autopsy-case control study was conducted using other annual volumes of the autopsy data records and a similar tendency was observed. Then, a live-case control study was undertaken of 86 subjects with IPF. A significantly higher odds ratio was noted among metal production workers and miners compared with healthy and hospital control subjects (1.37 and 1.34, respectively, p < 0.01), and also a significantly lower odds ratio among subjects who frequently eat fish. Taken together with results of recent in vitro studies, the intrapulmonary deposition of hazardous dusts, especially metallic dusts, appears to play at least a partial role in initiating IPF.

Adolescent↗
PubMed1994

[Clinical study of primary hyperparathyroidism--diagnosis, parathyroidectomy and late result of operation].

We retrospectively studied clinical problems for 55 patients with primary hyperparathyroidism who were operated on at our hospital. The chance to discovery of primary hyperparathyroidism and its accompanied symptoms were various. Other than classical symptoms, hypertension was noted in 12 patients and malignant tumors in 9. Forty-four percent of patients who had no bone related symptoms were found to have decreased bone mineral density (BMD). Even the patients with normal BMD were seen to increase the BMD, postoperatively. We thought that the parathyroidectomy was indicated for the asymptomatic patients with normal BMD. Biochemical investigation showed that positive rate were 50% for PTH-C, 94% for PTH-HS, 78% for intact PTH, 87% for serum total calcium and 98% for serum ionized calcium. Serum ionized calcium and intact PTH were useful for the diagnosis of patients who had normocalcemia or slight elevation of serum calcium. The sensitivity was 61% for ultrasound sonography (US) and 49% for computer tomography (CT) and scintigram, respectively. The detection rate of US and CT was positively related to the size of the parathyroid glands, but scintigram was not. The rate with which the parathyroid glands can be recognized during operation increased from 30% in the former group to 52% in the later group. As a result, 11% of the patients with adenoma had too much surgery and 29% of the patients with hyperplasia had too little surgery.

Adult↗
PubMed1994

[Two cases of advanced breast cancer effectively treated with chemoendocrine therapy and radiotherapy].

We reported 2 cases of breast cancer with lymph node metastasis treated with CAF (cyclophosphamide, adriamycin, 5-fluorouracil) and medroxyprogesterone acetate (MPA). Case 1 was stage IV [T4b, N3 M1 (lung)] and case 2 was stage IIIa (T1, N2, M0). The two cases responded well to CAF and MPA therapy in local and systemic lesions, and then underwent radiotherapy and lymph node resection without mastectomy. After these treatments, both cases were thought to be disease-free. Major side effects were allopecia, obesity, and leukopenia. These results suggest that combination chemoendotherapy, radiotherapy, and surgery can be utilized for most patients with moderately advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Racial difference in cardiac sarcoidosis incidence observed at autopsy.

The most commonly involved organ in sarcoid related death has been reported to be the lung in western countries, while it was the heart in the Japanese autopsy series. In order to verify this different pattern of death, autopsy records were reviewed in two United States institutions and in Japanese nation-wide data. In Japanese, male to female ratio was 1:2 and a high frequency of sarcoidosis in females over 50 years of age was observed. Male to female ratio in Caucasian sarcoidosis autopsy was nearly 1:1. In Afroamericans, it was nearly 1:2, and the age distribution showed that this female predominance was due to a high number of sarcoidosis in females over 40 years of age. The frequency of sarcoidosis in Caucasian autopsies was higher than in Japanese autopsies. The number of involved organs was smaller in Caucasians than in Afroamericans or in Japanese. The incidence of cardiac sarcoid granuloma in Japanese was significantly higher than that seen in Caucasians and Afroamericans. The commonest cause of death in sarcoidosis of Caucasians and Afroamericans was from non-sarcoid diseases, while the major cause of sarcoid-attributed death was pulmonary sarcoidosis in Afroamericans. Japanese showed the highest rate of cardiac sarcoid-attributed death. Possible factors relating to this high incidence of sarcoidosis in elderly females and the racial difference in cardiac sarcoidosis were discussed.

Adolescent↗
PubMed1994

[Clinical and autopsy studies on prognosis of sarcoidosis].

Prognosis of 435 sarcoidosis patients and epidemiologic features were studied in 320 autopsy cases. About 80-90% of Stage I or II patients showed spontaneous remission. The prognosis of Stage III patient was poor and corticosteroid therapy seemed to be rather ineffective. The proportion of sarcoidosis autopsy, relative to total autopsy cases, appears to be increasing. The number of female cases was about 2 times larger than that of males. Only 43.4% of the total autopsy cases had been diagnosed clinical sarcoidosis. Over 5 times more sarcoidosis patients than clinically diagnosed were estimated to exist. Approximately one half of the sarcoidosis autopsy cases were related to cardiac sarcoidosis.

Adolescent↗
PubMed1994

[Immunohistochemical studies on mycobacteria in tuberculous necrotizing granulomas].

For the purpose to know the pathogenesis of caseous necrosis in tuberculous lesion, authors compared the presence and the number of mycobacteria in the pulmonary tubercles of various histological types. Forty pulmonary tubercles obtained from 16 patients (9 males, 7 females; mean age 51) were examined. By Ziehl-Neelsen (ZN) method, acid-fast bacilli were detected in 40% of 5 proliferative, in 12.5% of 24 productive and none of 11 sclerotic granulomas. By immunohistological staining with anti-BCG antiserum, positive staining was observed in 60%, 87.5% and 91% of each type of granuloma, respectively. Types of necrosis were classified by silver-staining as necrosis after exudative reactions (EN), necrosis after productive reactions (PN) and filled materials after softening and liquification of necrotic lesions (LN). EN was observed in 24 tubercles, and mycobacteria were stained in 8% of EN by ZN method and in 75% by immunohistological method. PN was observed in 21 tubercles, and mycobacteria were detected in none and 5% of such type of necrosis by respective method. LN was observed in 28 tubercles, and mycobacteria were detected in 11% and 71% of these lesions by respective method. So, positive ratio by immunochemical method was significantly higher in EN and LN than in PN. Further, mycobacteria were stained with anti-BCG antiserum as granules and the number of such granules were much more numerous in EN and LN than in PN (p < 0.01). From these results, it was suggested that necrosis might occur by different mechanisms in exudative reactions and in productive reactions.

Adult↗
PubMed1993

Genomic characterization of the human DNA excision repair-controlling gene XPAC.

We have characterized the human DNA excision repair gene, XPAC (xeroderma pigmentosum group A complementing). This gene of approximately 25 kb consists of six exons. The 5'-flanking region of the gene has a CAAT box, but no TATA box. The region upstream from the coding sequence of exon 1 is G + C rich (73%), and has a GC box. Transcriptional mapping analysis suggested that there is one major transcription start point (tsp). The presence of two polyadenylation signals suggests that the two XPAC mRNAs with different 3' untranslated regions in normal human cells are due to alternative polyadenylations. The promoter activity, measured by transient expression of the cat gene with the 5' flanking regions, indicated the presence of a functional promoter.

Amino Acid Sequence↗
PubMed1993

Importance of E-selectin (ELAM-1) and sialyl Lewis(a) in the adhesion of pancreatic carcinoma cells to activated endothelium.

Adhesion molecules involved in attachment between human pancreatic carcinoma and activated endothelial cells in vitro were investigated. Basal adhesion occurred between 6 pancreatic carcinoma cell lines and unstimulated human umbilical vein endothelial cells (HUVEC), and augmented basal adhesion to activated HUVEC was only seen when pancreatic cancer cells expressed sialyl Lewisa (SLea) and sialyl Lewisx (SLex). Activation of HUVEC with interleukin 1-beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha), but not with interferon-gamma (IFN-gamma), generated the augmentative basal adhesion. Dose dependence and additive effect were observed in augmentation of the basal adhesion induced by IL-1 beta and/or TNF-alpha. Increase in adhesion correlated with up-regulation of the surface E-selectin (or ELAM-1) on HUVEC, and was evident at both 25 degrees C and 4 degrees C. Anti-E-selectin and anti-SLea blocked the augmented attachment, whereas anti-SLex, an antibody against another known ligand for E-selectin, did not. The collective evidence indicates that attachment between pancreas carcinoma cells and activated endothelial cells is regulated by cytokines such as IL-1 beta and TNF-alpha, and is mediated by SLea on pancreas carcinoma and E-selectin on endothelial cells. These molecules may be of significant importance in blood-borne metastasis of pancreatic carcinoma cells to inflamed sites.

Aged↗
PubMed1993

Absence of bcl-2 expression by activated CD45RO+ T lymphocytes in acute infectious mononucleosis supporting their susceptibility to programmed cell death.

bcl-2 proto-oncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death (apoptosis). There is now increasing evidence that regulation of bcl-2 expression is a determinant of life or death in normal lymphocytes. We have recently described that activated (CD45RO+) CD4+ and CD8+ T cells in acute infectious mononucleosis (IM) undergo apoptotic cell death on culturing, indicating an activation-driven cell death of mature T cells. In this work, we examine bcl-2 expression by activated T cells in acute IM using a flow-cytometric analysis with an anti-bcl-2 monoclonal antibody (MoAb). It was consistently observed that most T cells from acute IM patients displayed only much less bcl-2, while normal T cells expressed bcl-2 relatively strongly. Multicolor analysis showed that bcl-2-lacking T cells in acute IM were restricted to the CD45RO+ (activated) populations of CD4+, as well as CD8+ T cells. In contrast, the relatively intense levels of bcl-2 were expressed in both CD45RO+ and CD45RO- T-cell populations from normal subjects. This marked difference in bcl-2 expression of CD45RO+ T cells between acute IM and normal controls was also confirmed by Western blot analysis. Activated (CD45RO+) T cells with low bcl-2 expression, but not bcl-2-expressing CD45RO- T cells, in acute IM patients were found to die easily when cultured without added growth factors. However, in normal individuals, both CD45RO+ and CD45RO- T cells were relatively stable on culturing. These findings suggest that lack of bcl-2 expression by activated (CD45RO+) T cells in acute IM might be associated with their susceptibility to programmed cell death.

Adolescent↗
PubMed1993

Cytokine regulation of cell-to-cell interactions in lymphokine-activated killer cell cytotoxicity in vitro.

The permanent pancreas carcinoma cell line, PCI-24, was developed in order to analyse cytokine regulation on pancreas carcinoma and lymphokine-activated killer (LAK) cell interaction. PCI cells expressed ICAM-1 and HLA-ABC, but not HLA-DR antigens. PCI cells showed augmented ICAM-1 and HLA-ABC expression when incubated with interferon gamma (IFN gamma) and tumour necrosis factor alpha. A similar but weak augmentary effect on the HLA-ABC and ICAM-1 surface expression was seen with interleukin-1 beta treatment. Natural attachment of LAK to PCI cells was augmented by recombinant IFN gamma in close association with ICAM-1 up-regulation on PCI cells. In addition, natural attachment was significantly inhibited by anti-LFA-1 and anti-ICAM-1 antibody treatments. Cytotoxicity of the LAK cells against PCI cells was also significantly inhibited with the same treatment. Thus, the attachment of LAK cells to PCI cells through LFA-1/ICAM-1 molecules appeared to be essential for the cytotoxicity for PCI cells. Pretreatment of PCI cells, but not of LAK cells, with IFN gamma or other cytokines resulted in a decrease of susceptibility for LAK cell cytotoxicity. The decreased susceptibility inversely correlated with HLA-ABC expression on the PCI cells. The collective evidence indicates that, although LAK cell attachment to pancreas carcinoma cells through the LFA-1/ICAM-1 molecule is augmented by IFN gamma, IFN gamma treatment of pancreas carcinoma cells reduces LAK cell cytotoxicity possibly through an increase in HLA-ABC or a regulation of molecules closely associated to HLA-ABC expression.

Aged↗
PubMed1993

Physiological characteristics related to endurance running performance in female distance runners.

The purpose of the present study was to determine the relationships between running velocity (v) in a 3000-m race and various physiological parameters. The parameters measured among 57 female distance runners during a treadmill running test were v at the lactate threshold (v-Tlac), oxygen uptake (VO2) at the lactate threshold (VO2 at Tlac), v at the onset of blood lactate accumulation (v-OBLA), VO2 at OBLA, running economy (steady-state VO2 at a standard v of 4 m s-1), maximal oxygen uptake (VO2 max) and v at VO2 max (v-VO2 max). The v-OBLA was the blood lactate variable with the strongest correlation with v in a 3000-m race (r = 0.78, P < 0.001). The second strongest correlation was with v-Tlac (r = 0.77, P < 0.001). Although v-VO2 max was strongly correlated with v over 3000 m (r = 0.75, P < 0.001), further analysis by stepwise multiple regression indicated that a combination of v-OBLA, VO2 at Tlac and v-Tlac could account for 73.2% of the variability in v over 3000 m, whereas v-OBLA on its own explained 61.5%. Blood lactate variables can account for a reasonably large part of the variance in v over 3000 m. Also, v-VO2 max can be used as a non-invasive predictor of distance running performance.

Adolescent↗
PubMed1993

Reperfusion after brief ischemia disrupts the microtubule network in canine hearts.

Histological changes in the stunned myocardium are believed to be minimal. This study examined whether cytoskeletal structures of microtubules are disrupted in the stunned myocardium. In 38 dogs, the left anterior descending coronary artery was occluded for 15 minutes and reperfused to produce the stunned myocardium. Microtubules were stained immunohistochemically. In intact myocardium, microtubules appeared as a filamentous network throughout the cytoplasm and encircled the nucleus. This pattern was not affected by 15 minutes of ischemia. One hour of reperfusion, however, disrupted microtubular structure substantially (disruption score in the endocardium, 53.4 +/- 6.0%) although actin filaments remained intact. Microtubular structures were reconstituted 1-3 days after reperfusion, showing supernormal immunoreactivity. Five days after reperfusion, the pattern of microtubular staining was normal. In another protocol, the role of Ca2+ during reperfusion in microtubular disruption was examined. When intracoronary infusion of EDTA (1.67 mumol/kg body wt per minute) was performed during the initial 10 minutes of reperfusion, myocardial stunning was attenuated. The fractional shortening in the perfused area after 1 hour of reperfusion was 20.1 +/- 1.2% versus 11.5 +/- 0.5% in the control condition (p < 0.05), and the microtubular disruption score was lower (12.6 +/- 1.4%). Although intracoronary infusion of calcium chloride (9 mumol/kg body wt per minute) for 10 minutes in nonischemic hearts increased contractile function (fractional shortening, 25.3 +/- 2.0%), it severely disrupted microtubular networks (microtubular disruption score, 64.0 +/- 10.6%). We conclude that microtubules supporting the structural integrity of myofibrils and other organelles are reversibly disrupted by reperfusion after brief ischemia probably through calcium overload.

Animals↗
PubMed1993

[Pathogenesis of idiopathic interstitial pneumonia: epidemiological approach from dust theory].

In order to elucidate the factors relating to the pathogenesis of idiopathic interstitial pneumonia (IIP), an epidemiological analysis was carried out on 1880 autopsy cases of acute and chronic froms of IIP which were included in the Japanese Pathological Autopsy Records. The disease was found in a high frequency in high age groups, especially in males, and was more prevalent in agricultural than in urbanized districts of Japan. Studies on the occupational distribution demonstrated a significantly higher rate of the disease in the occupations in which workers might have been exposed to harmful dusts or fumes. Other studies on autopsy cases also reported a high incidence of IIP in occupationally exposed groups, and a clinical case control study again reported a high incidence of IIP in the occupational group including production metal workers. Together with the previous studies on element analysis of IIP tissue, exposure to harmful dusts including metallic compounds is a possible trigger, at least partly, for idiopathic interstitial pneumonia.

Adolescent↗
PubMed1993

Involvement of IL-7 in the development of gamma delta T cells in the thymus.

The effect of IL-7 on the growth of thymic T lymphocytes was investigated by adding recombinant IL-7 into cell suspension cultures and submersion organ cultures (SOC) of murine fetal thymuses (FT) and newborn thymuses (NBT). FT and NBT were obtained from C57BL/6 mice at day 15 of gestational age and at day 3 after birth, respectively. In both cell suspension cultures and SOC, addition of IL-7 highly improved the cell recovery. In cell suspension cultures, addition of IL-7 resulted in the growth of gamma delta T-cells from FT-cells, whereas the same cytokine promoted the growth of both alpha beta and gamma delta T-cells from NBT-cells. These results may indicate that this cytokine is able to support the proliferation of T-cells of both alpha beta and gamma delta lineages. In marked contrast, in SOC, addition of IL-7 resulted in the growth of gamma delta T-cells not only in FT but also in NBT, despite the fact that the SOC of NBT without exogenous cytokine exclusively promoted the growth of alpha beta T-cells. A similar effect was also seen when IL-2 was added to NBT-SOC, though the skewing to gamma delta lineage was not so strong as in the case of IL-7. In addition, we found that IL-7 mRNA is expressed in the day 15 FT at a much higher level than in the adult thymus. These results strongly suggested that the production of a large amount of IL-7 synthesized in the FT is one of the major factors leading to the generation of gamma delta T-cells in FT.

Animals↗
PubMed1992

A murine thymic stromal cell line which may support the differentiation of CD4-8- thymocytes into CD4+8- alpha beta T cell receptor positive T cells.

A fibroblastoid cell line TSt-4 was established from fetal thymus tissue of C57BL/6 mice. When fetal thymus (FT) cells or CD4-8- (DN) cells of adult thymuses were cultured on the monolayer of TSt-4, a considerable proportion of lymphocytes expressed CD4 or both CD4 and CD8 within 1 day, and the CD4+CD8- cells were maintained further while the CD4+8+ cells disappeared by Day 5. A large proportion of cells generated from DN cells but not FT cells was shown to express CD3 and T cell receptor alpha beta. Addition of recombinant interleukin (IL)-7 into the cultures resulted in a marked increase of cell recovery without virtual change in differentiation process of alpha beta lineage. The present work strongly suggests that thymic fibroblasts play an important role in T cell differentiation and IL-7 contributes to supporting proliferation of differentiated cells.

Animals↗
PubMed1992

In vitro induction of IgG anti-DNA antibody from high density B cells of systemic lupus erythematosus patients by an HLA DR-restricted T cell clone.

An HLA-DR restricted T cell clone (26G11) which recognized a lymphoid cell-derived autoantigen associated with DR4 molecule was shown to induce not only autologous but also allogenic DR4+ B cells to produce large amounts of antibodies of the IgG and IgM classes. Using the helper activity of this clone, we investigated the mechanism of anti-DNA antibody production in DR-matched patients with systemic lupus erythematosus (SLE). When cultured with 26G11 cells, B cells from DR-matched normal control subjects produced large amounts of IgM anti-DNA antibody, but did not produce IgG anti-DNA antibody which is thought to have a pathological role in SLE. In contrast, B cells from DR-matched patients with active SLE spontaneously produced a fairly large amount of IgG anti-DNA antibody, and the production was augmented by the T cell clone. Little IgG anti-DNA antibody was produced by the B cells of patients with inactive SLE in either the presence or absence of T cell clone. We next fractionated B cells into low density B (LD-B) and high density B (HD-B) cells by centrifugation on discontinuous Percoll density gradients. IgG anti-DNA antibody was spontaneously produced by LD-B cells of active SLE patients but not by those either of inactive SLE patients or normal controls. On the other hand, although IgG anti-DNA antibody was not spontaneously produced by the HD-B cells of both active and inactive SLE patients, it could easily be induced by their culture with the T cell clone. Our results clearly show the existence of IgG anti-DNA antibody-producing B cells in the peripheral blood of SLE patients irrespective of their disease activity and suggest that autoreactive T cells may play a pathogenic role in SLE through the induction of autoantibody production.

Antibodies, Antinuclear↗