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Yoshikazu Kawakami

Publications and source records attributed to Yoshikazu Kawakami.

17 recordsLinked to original sources
PubMed2005

Comparative simulation of gas transport in airway models of rat, dog, and human.

Although a number of animal studies have been conducted to investigate the toxic effects of gaseous pollutants on human airways, the anatomical and physiological differences between animals and humans represent a challenge in extrapolating the animal data to humans. The aim of this study was to examine how interspecies anatomical and physiological differences influence the transport of the inhaled gases throughout the airways and alveoli. We designed mathematical airway models of three mammalian species, rats, dogs, and humans, in which interspecies differences in airway dimensions and respiratory patterns were taken into account. We then simulated the bulk flow of three gases (ozone [O(3)], nitrogen dioxide [NO(2)], and sulfur dioxide [SO(2)]) and obtained the intra-airway concentrations of the gases and the amount absorbed using these models. For all three gases, both real-time and mean concentrations in the upper and lower airways were higher in humans when compared with rats and dogs. For example, the mean concentration of O(3) in the 5th bronchi of humans was 3 and 12 times higher than in rats and dogs, respectively. Similarly, the amount of absorbed gases corrected for airway surface area was again higher in the upper and lower airways of humans than the other two species. Sensitivity analysis indicated that tidal volume, respiratory rate, and surface area of the upper and lower airways had significant impact on the results. In conclusion, kinetics of inhaled gaseous substances vary substantially among animals and humans, and such variations are, at least partially, the result of anatomical and physiological differences in their airways.

Air Pollutants↗
PubMed2005

Pleural involvement of dialysis-related amyloidosis.

Two cases of pleural involvement of dialysis-related amyloidosis (DRA) with pleural effusion are presented. DRA is one of the most important complications in long-term dialysis patients and beta2-microglobulin is the principal protein component of DRA, but pleural deposition of beta2-microglobulin amyloid has not yet been reported. To the best of the authors' knowledge, this is the first case report of pleural involvement of DRA presenting with pleural effusion. This case study suggests that pleural involvement of DRA should be considered when exudative pleural effusion is observed in patients undergoing long-term dialysis.

Aged↗
PubMed2004

[A case of pulmonary embolic metastasis of choriocarcinoma presenting with multiple pulmonary infiltrative shadows].

A 34-year-old woman visited our hospital complaining of dry cough. Chest radiography and computed tomography showed bilateral multiple infiltrative shadows over the lung field. After an initial diagnosis of pneumonia, antibiotics were administered, but the therapy failed to improve the symptoms and abnormalities observed on the chest radiograph. The patient was then admitted to our hospital. The bronchoalveolar lavage fluid (BALF) was slightly bloody, but we were not able to make any specific findings in BALF. In order to confirm the pathological diagnosis, video-assisted thoracoscopic lung biopsy was performed aiming at the right middle and lower lobes. There were bleeding pulmonary infarctions in a biopsy specimen from the right middle lobe. Atypical cells positive for human chorionic gonadotropin (hCG) proliferated in the pulmonary arteries, and so a diagnosis of pulmonary embolic metastasis of choriocarcinoma was made. After the diagnosis, it became clear that urine and serum hCG values were very high. The patient has since received systemic chemotherapy in the gynecology unit at our hospital. Pulmonary embolic metastasis of choriocarcinoma diagnosed by video-assisted thoracoscopic lung biopsy has never been reported in the literature. However, early hCG measurement may have detected this syndrome in the earlier stages, and pulmonary metastasis of choriocarcinoma should be considered in the differential diagnosis of women with past pregnancy presenting with intractable multiple pulmonary shadows.

Adult↗
PubMed2002

Expression and alteration of ras and p53 proteins in patients with lung carcinoma accompanied by idiopathic pulmonary fibrosis.

BACKGROUND: The ras oncogene and the p53 tumor suppressor gene play important roles in the carcinogenic process of lung carcinoma. The authors evaluated whether alterations of the ras and p53 proteins may contribute to the development of lung carcinoma in patients with idiopathic pulmonary fibrosis (IPF) and whether such alterations may explain the high incidence of lung carcinoma among patients with IPF. METHODS: Lung tissues were obtained from 35 patients who had IPF without complications of lung carcinoma and from 36 patients who had IPF with complications of lung carcinoma. Altered expression of ras and p53 proteins was evaluated by immunohistochemistry, and mutations of both genes were evaluated by polymerase chain reaction-single strand conformation polymorphism and sequencing analyses. RESULTS: The frequency of expression of ras protein in type II alveolar pneumocytes was significantly greater in lung tissues from patients with IPF who had lung carcinoma compared with lung tissues from patients with IPF who did not have lung carcinoma (75% vs. 40%, respectively; P < 0.01). K-ras point mutation in codon 12 (GGT to GTT transversion) was detected in lung tissue with interstitial pneumonia, in which ras protein was overexpressed in type II alveolar pneumocytes obtained from 2 of 41 patients with IPF complicated by lung carcinoma, causing amino acid substitution (Gly to Val) in both patients. A p53 mutation was detected in three of six lung tissue samples from patients who had IPF lung with positive p53 immunoreactivity, and multiple mutations were detected in two samples. CONCLUSIONS: Expression of ras protein in type II alveolar pneumocytes and mutation in the codon 12 of K-ras gene in lung tissue may contribute to the induction of lung carcinoma in patients with IPF. Furthermore, the presence of multiple mutations in the p53 gene may explain the high incidence lung carcinoma in patients with IPF.

3T3 Cells↗
PubMed2002

Occurrence of farmer's lung disease is relevant to meteorological conditions: a 20-year follow-up field survey analysis.

BACKGROUND: A field survey on farmer's lung disease (FLD) in a dairy farming community in the northernmost district of Japan has been in progress since 1978. METHODS: The correlation between the number of FLD occurrences year by year and dairy farming conditions and meteorological data were compared. RESULTS: Thirty-four FLD cases had occurred in a 20 years period. Average number of days below freezing during the harvest season the year prior to FLD occurrence were significantly smaller than other years (2.1 +/- 0.7 [SE] days, 4.6 +/- 0.7 days, P < 0.05, respectively). Average annual sum of the sunlight hours in the years before the years with FLD occurrence was significantly smaller than those without FLD occurrence (1457.1 +/- 114.0 hr, 1811.3 +/- 97.7 hr, P < 0.05, respectively) and was also significantly smaller for the sunlight hours during a harvest season (821.9 +/- 60.2 hr, 1023.2 +/- 52.7 hr, P < 0.05, respectively). CONCLUSIONS: Temperature and sunlight hours closely associated with the FLD occurrence.

Dairying↗
PubMed2002

Enhanced complement sensitivity of NK-T cells in murine thymus and spleen associated with presence of serum immunoglobulin.

In vitro treatment of thymocytes and splenocytes with rabbit complement (C') alone induced significant reductions in the proportion of NK-T cells in murine system. The reduction appeared to be prominent in the thymic NK-T cells compared to that in splenic NK-T cells. No reductions were detected in other populations, such as T, B and NK cells. Thus, NK-T cells lineage-specifically showed the enhanced C' sensitivity. However, NK-T cells in T cell receptor (TCR) transgenic mice of RAG-/- background that lack B cells and antibodies exhibited no C' sensitivity. On the other hand those from the same TCR transgenic mice of RAG intact background that have a normal population of B cells and antibodies showed the C' sensitivity similar to that in normal mice. These findings suggest that the enhanced C' sensitivity observed in the NK-T cell population is associated with the NK-T specific autoantibodies. Indeed, we found that a subset of NK-T cells in the thymus bound mouse immunoglobulins. Similar observations were obtained with several strains of lupus model mice, some of which show a decrease of NK-T cells with aging. Possible roles of the enhanced C' sensitivity of NK-T cells in pathophysiological conditions in various mouse strains including lupus models are discussed.

Animals↗
PubMed2002

Tissue hypoxia in sleep apnea syndrome assessed by uric acid and adenosine.

STUDY OBJECTIVE: Although the overnight increase in urinary uric acid/creatinine ratio (DeltaUA/Cr) is considered by some to be a marker of tissue hypoxia in patients with obstructive sleep apnea-hypopnea syndrome (OSAS), this index is not universally accepted. The purpose of this study was to confirm the validity of DeltaUA/Cr as a marker of tissue hypoxia by measuring the plasma level of adenosine during sleep, and also to test the hypothesis that the heart rate (HR) response to apnea is a determinant of tissue hypoxia. DESIGN: Intergroup comparative study. SETTING: A university hospital, Sapporo, Japan. PATIENTS: Eighteen patients with OSAS who had apnea-associated, moderate-to-severe arterial desaturation. The patients were classified into two groups: the DeltaUA/Cr-positive group, who were considered to have tissue hypoxia, and the DeltaUA/Cr-normal group, who were not. MEASUREMENTS AND RESULTS: Although there were no significant differences between two groups of the patients in either arterial desaturation parameters or the apnea-hypopnea index, the plasma level of adenosine during sleep was significantly higher in the DeltaUA/Cr-positive group than in the DeltaUA/Cr-normal group. Successful treatment with nasal continuous positive airway pressure significantly decreased both DeltaUA/Cr and the plasma level of adenosine only in the DeltaUA/Cr-positive group. The magnitude of the HR increase after the termination of apnea was significantly smaller in the DeltaUA/Cr-positive group. CONCLUSIONS: DeltaUA/Cr is a marker of tissue hypoxia, which does not necessarily parallel arterial desaturation indexes in OSAS. Intersubject variability in the HR response to apnea may explain the discrepancy between tissue hypoxia and arterial desaturation indexes.

Adenosine↗
PubMed2002

A case of diabetes, deafness, cardiomyopathy, and central sleep apnea: novel mitochondrial DNA polymorphisms.

We describe a case of diabetes mellitus complicated by neurosensory hearing loss, cardiomyopathy, and sleep apnea syndrome. A 48-year-old man who was admitted for treatment of a lacerated tendon of the right shoulder was also found to require preoperative control of diabetes, a condition that had been diagnosed 4 years earlier. The family pedigree suggested maternal inheritance of diabetes. The patient also had neurosensory hearing loss and the central type of sleep apnea syndrome. His myocardium was hypertrophic and the ultrastructural analysis showed morphologically abnormal mitochondria. On the basis of the apparent characteristic manifestations, we speculated that he had a mitochondrial disease. To elucidate the responsible mutation of mitochondrial DNA, we sequenced the patient's entire mitochondrial DNA derived from blood leukocytes and found 40 sequence variants. Three of those, 5466 A/G, 7912 G/A, and 10601 T/C, have not yet been reported. Nine of the 40 variants were accompanied by an amino acid replacement, including 5466 A/G. Although we could not determine the most significant mutation, the variants of mitochondrial DNA may have been associated with this patient's unusually variable clinical manifestations.

Cardiomyopathies↗
PubMed2002

Troglitazone ameliorates abnormal activity of protein tyrosine phosphatase in adipose tissues of Otsuka Long-Evans Tokushima Fatty rats.

Protein tyrosine phosphatases (PTPases) play an essential role in the regulation of steady-state phosphorylation of the insulin receptor and other proteins in the insulin signaling pathway. To determine the role of PTPases in adipose tissue in the development into an insulin-resistant state, we examined PTPase activities and protein levels of three major candidate PTPases in adipose tissues of 26-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Particulate PTPase activities in visceral and epididymal adipose tissues of OLETF rats were increased compared to those in Long-Evans Tokushima Otsuka (LETO) rats, non-insulin-resistant controls. Cytosolic PTPase activities in these tissues were conversely decreased in OLETF rats. In subcutaneous adipose tissues, those changes were not observed. Western blot analysis showed that the amounts of leukocyte antigen-related PTPase (LAR), PTPase 1B (PTP1B), and src homology 2-containing PTPase (SH-PTP2) were increased in particulate fractions of visceral and epididymal fat of OLETF rats. On the other hand, those in the cytosolic fractions were slightly decreased. Troglitazone was administered to OLETF rats to examine the effect of the drug on the changes in PTPase activity and distribution. Troglitazone treatment restored those alterations in PTPase activity in the particulate fraction and the amounts of LAR, PTP1B and SH-PTP2 in both fractions of visceral and epididymal adipose tissues of OLETF rats. Although it remains unknown whether such effects of troglitazone are mediated by peroxisome proliferator-activated receptor y, these data provide useful information for understanding the significance of PTPase in insulin-resistant rats and the molecular mechanism of troglitazone action.

Adipose Tissue↗
PubMed2002

[Genetic background of sarcoidosis--special reference to HLA].

A comprehensive epidemiological study (ACCESS) recently conducted in the United States has recognized modest familial aggregation of sarcoidosis. Therefore, genetic factors, in particular human leukocyte antigens (HLAs) are believed to be important determinants of susceptibility to sarcoidosis. A previous case-control study on Japanese population has postulated that an amino acid, serine, at position 11 of beta subunit of HLA-DR confers susceptibility to sarcoidosis. Whereas, a more recent study suggests that protective HLA-DR alleles, which encode the DR1 and DR4 antigens, were found to share characteristic small hydrophobic residues at the same position. Meanwhile, the first genome scan on sarcoidosis has found the highest linkage score in the class III region, where HLA-DR genes do not exist. Complete clarification of genetic mechanisms of sarcoidosis awaits the precise identification of causative antigens, if any.

Genetic Markers↗
PubMedDate not supplied

Topoisomerase inhibitor-induced apoptosis accompanied by down-regulation of Bcl-2 in human lung cancer cells.

BACKGROUND: Anticancer drug-induced apoptosis is one of the important mechanisms in the effectiveness of chemotherapy. In this study, we investigated apoptosis induced by topoisomerase inhibitors and its relationship with chemosensitivity, the expression of Bcl-2 family proteins and p53 status in human lung cancer cells. MATERIALS AND METHODS: A total of six human lung cancer cell lines, i.e., two small cell lung cancer (SCLC) and four non-small cell lung cancer (NSCLC) cell lines, were used. For induction of apoptosis, these cell lines were treated with SN-38 (DNA topoisomerase I inhibitor) or etoposide (DNA topoisomerase II inhibitor). Drug sensitivity was determined using a microculture tetrazolium assay. The rates of apoptosis and alterations of Bcl-2 and Bax expression were analyzed by flow cytometry. RESULTS: Apoptotic cells increased in a time-dependent manner after exposure to topoisomerase inhibitors. Induction of apoptosis was accompanied by the down-regulation of Bcl-2 expression, but there was little alteration of Bax expression. These events were significantly more extensive in SCLC cell lines, which are more sensitive to topoisomerase inhibitors, than in NSCLC cell lines, which are more resistant to these inhibitors. However, neither induction of apoptosis nor chemosensitivity correlated with p53 status in the lung cancer cell lines studied. CONCLUSION: The more extensive induction of apoptosis with Bcl-2 down-regulation in SCLC than in NSCLC might explain, at least in part, the higher clinical sensitivity to topoisomerase inhibitors in the former disease.

Antineoplastic Agents, Phytogenic↗