It has been shown that a statin (3-hydroxy-3-methyl-glutaryl coenzyme reductase inhibitor) enhances a suppressive effect of angiotensin Ⅱ type 1 receptor (AT 1-R) blocker (ARB) on injury-induced transforming growth factor (TGF)-β expression in kidneys. We have shown that TGF-β plays a crucial role in the development of liver fibrosis. In this study, we tested whether a combinatory use of a statin (pitavastatin) and an ARB (candesartan) may further inhibit liver fibrogenesis in carbon tetrachloride (CCl₄)-treated rats. Candesartan (8 mg/kg/day) significantly suppressed injury-induced TGF-β1 expression in livers, and attenuated fibrogenesis, as evaluated by masson-trichrome staining and hydroxyproline content in livers. Pitavastatin (2 mg/kg/day) alone did not affect liver fibrogenesis. However, it enhanced significantly the suppressive effects of candesartan on TGF-β1 expression and fibrogenesis. Although we do not know the underlying molecular mechanisms at this moment, these results suggest that a combinatory use of a statin and an ARB may confer beneficial effects on human liver fibrogenesis.

View full abstract

To test the hypothesis that tolerance to central hypovolemic stress is diminished with a reduced sensitivity of cardiac baroreflex in young and old men, twenty-four healthy elderly male subjects (67.5±0.9 yrs) and 24 young male subjects (22.4±0.4 yrs) underwent a 21 min bout of ramped lower body negative pressure (LBNP) (0 to -60 mmHg, 10 mmHg each for 3 min). Heart rate (HR), blood pressure, thoracic impedance (Z_o) and calf circumference were measured throughout the experimental period. The sensitivity (BRS) of arterial baroreflex control of the cardiac interval was calculated from spontaneous changes in beat-to-beat arterial pressure and the RR interval during the LBNP test. The occurrence of presyncope episodes during LBNP was 16.7% in elderly subjects and 37.5% in young subjects. The changes of HR, blood pressure, Z_o and calf circumference in the young (Young fainter group) and the elderly (Elderly fainter group) subjects who showed presyncope during LBNP did not differ from those in the subjects (Young and Elderly nonfainter groups) who did not show presyncope. The steady-state HR responses to the changes of Z_o during LBNP did not differ among the four groups. In young and elderly subjects, the baseline values of BRS in the fainter groups tended to be smaller than those in the nonfainter groups, and the difference in the young group was significant (P<0.05). No LBNP-related change of BRS was observed in elderly subjects, whereas a gradual LBNP-related decrease was observed in young subjects. These findings suggest that 1) aging does not increase intolerance to central hypovolemic stress induced by a given LBNP, 2) the reduced vagal BRS is related partly to low LBNP tolerance in young and elderly men.

View full abstract

Metallothionein (MT) is a low molecular weight protein, rich in cystein residues, and induced by stimulation with several stresses such as heavy metals, chemical agents, oxygen radicals and irradiation. It is involved in metal metabolism, detoxification and radical scavenging and also participates in immune responses. In this communication, to study the role of MT in immune responses, we analyzed immune functions, especially macrophage functions in MT-knock out (MT-KO) mice in vitro. When compared with wild type counterpart (MT-WT) mice, macrophages from MT-KO mice showed a defect of phagocytic and antigen-presenting activity. Cytokine productions such as IL-1α, IL-6, IL-10 and IL-12 were reduced in macrophages from MT-KO mice. Furthermore, the expressions of CD80, CD86 and MHC class Ⅱ molecules were also reduced in macrophages from MT-KO mice. No obvious dysfunction was observed in T cells and B cells. These results suggest that MT plays an important role in the regulation of immune responses, especially macrophage functions.

View full abstract

This study attempted to clarify gender differences associated with mental health consultations at a health care center (X center) that services 40,638 (34,491 men and 6,147 women) workers and is operated by a Japanese company. Data from 940 subjects (790 men and 150 women) undergoing first-time consultation at the X center between April 1996 and March 2001 were collected from the database. After matching age (within 3 years) and occupation between the male and female groups by pairing, 58 men and 58 women were compared. There was no difference in work inefficiency and diagnosis between the two groups, but the referral route of the first consultation differed significantly: males were more frequently self-referred. Fewer female than male patients were found to have work-related complaints. With regard to these work-related complaints, inadequate relationships, and especially conflicts with superiors, were found to be the most frequent cause among patients of both genders, although differences in the content of these complaints did exist.

View full abstract

The purpose of this study was to investigate the limitations of lip-reading advantages for Japanese young adults by desynchronizing visual and auditory information in speech. In the experiment, audio-visual speech stimuli were presented under the six test conditions: audio-alone, and audio-visually with either 0, 60, 120, 240 or 480 ms of audio delay. The stimuli were the video recordings of a face of a female Japanese speaking long and short Japanese sentences. The intelligibility of the audio-visual stimuli was measured as a function of audio delays in sixteen untrained young subjects. Speech intelligibility under the audio-delay condition of less than 120 ms was significantly better than that under the audio-alone condition. On the other hand, the delay of 120 ms corresponded to the mean mora duration measured for the audio stimuli. The results implied that audio delays of up to 120 ms would not disrupt lip-reading advantage, because visual and auditory information in speech seemed to be integrated on a syllabic time scale. Potential applications of this research include noisy workplace in which a worker must extract relevant speech from all the other competing noises.

View full abstract

Following the discovery of an immunosuppressive substance isolated from one of the entomopathogenic fungi 'vegetable wasps and plant worms', FTY720, whose immunosuppressive action is more potent than that of cyclosporin, was developed. In contrast to classical immunosuppressants such as cyclosporin, FTY720 does not affect the growth, maturation and activation of lymphocytes, but causes a reduction in the number of circulating lymphocytes as a result of enhanced homing of lymphocytes to the secondary lymphoid organs. It has recently been reported that FTY720 is phosphorylated in vivo by sphingosine kinase, and the phosphorylated FTY720 is a ligand of the receptors of sphingosine 1-phosphate (SIP), which are G-protein-coupled receptors. SIP has been recognized most prominently as a platelet-derived lipid mediator which regulates several functions of endothelial and smooth muscle cells. In addition, recent studies have suggested the crucial roles for SIP in immunological, and inflammatory modulation.

View full abstract

A remarkable increase has occurred in the incidence of prostate cancer in many countries including Japan. For early detection of prostate cancer, mass screening was initiated in many areas in Japan. We began screening for prostate cancer in 1993 in the Yahata area. Prior to 1996, prostate cancer screening consisted of interview, digital rectal examination, measurement of prostate specific antigen and transrectal ultrasonography. Since 1997, only an interview and PSA measurement has been performed. This screening program is provided free of charge. The men who had abnormal findings on the first screening were advised to visit an urologist for further examination. Over a period of 10 years, we detected prostate cancer in 6 out of 903 men (0.64%). Of those 6 patients, 5 had early localized cancer. In conclusion, we feel it is necessary to increase the number of subjects and visiting rate to an urologist, and to determine the diagnostic strategies including prostate biopsy on the second screening. In addition, the effectiveness of screening should be elucidated.

View full abstract

The case is a 62 years old male. No polyposis was found by upper gastrointestinal endoscopy or barium enema examination performed at the time of cholecystectomy in March 1994. Symptoms such as dysgeusia, diarrhea, loss of hair and atrophy of nails began to appear from May. Examination of the digestive tract performed in October revealed clustered polyposis in the stomach, duodenum, small intestine and large intestine. Pathologically, all the polyps were found to be of the juvenile type, so a diagnosis of Cronkhite-Canada syndrome (CCS) was made. Histologic patterns of rectal polyp after polypectomy showed well differentiated adenocarcinoma continuous with the juvenile type polyp. The above-mentioned symptoms improved with the clinical course. At present, 6 years after the development of the disease, no recurrence of polyposis in the stomach and large intestine has been found. Our results suggest that ectodermal changes and lesions of the digestive tract in CCS appear and disappear in a short time.

View full abstract

Rehabilitation and return-to-work are important problems for laryngectomized patients. Here, we report 2 cases of laryngectomized middle-aged men, and discuss the role of otolaryngologists from the viewpoint of an industrial physician. The first case is a 55-year-old post-office male clerk, who underwent radical and reconstructive surgery for hypopharyngeal carcinoma. He started light work following 3-month-rest at home after discharge, and fully returned to his previous work 3 years later. The second case is a 50-year-old mailman who also underwent radical and reconstructive surgery for hypopharyngeal carcinoma. He could not return to work because of the recurrence of tumor during rehabilitation. In such cases, comprehensive management including medical, mental and social supports is essential according to the occupational environment. Industrial otolaryngologists should play an important role in rehabilitation and return-to-work of laryngectomized patients.

View full abstract