Association of gastroesophageal reflux disease with weight gain and apnea, and their disturbance on sleep.

Obesity is a common predisposition to gastroesophageal reflux disease (GERD) and obstructive sleep apnea syndrome (OSAS). By statistical analysis of the respondents to a questionnaire that was distributed to members of the Kansai Rugby Association, we examined whether weight gain increased the incidence of these diseases and whether GERD alone disturbs sleep. Prevalence distribution of GERD by age differed from another survey, which suggests that predispositions other than age may contribute to GERD. Weight gain tended to increase the incidence of GERD. In our epidemiological study, both GERD (particularly nocturnal reflux) and OSAS significantly contributed to sleep disturbance. Although GERD alone seemed to be one of several independent factors of sleep disturbance, it was not a weak factor.

Esophageal pressure and apnea hypopnea index in sleep-disordered breathing.

Severity of negative esophageal pressure (Pes) and apnea hypopnea index (AHI) were investigated in six cases of upper airway resistance syndrome (UARS) and 11 cases of obstructive sleep apnea syndrome (OSAS). The severity of negative Pes was represented by the highest peak (Pes Max) and the number of increased episodes (more than 13.5 cmH2O) per h (NPesI13.5). There was no significant correlation between Pes indices and AHI. Pes Max and NPesI13.5 were not different among severe OSAS (AHI > 30), mild OSAS (AHI < 30) and UARS. Apnea hypopnea index failed to represent the severity of negative Pes, which is an important aspect of the pathophysiology of sleep-disordered breathing.

The relationship between esophageal pressure and apnea hypopnea index in obstructive sleep apnea-hypopnea syndrome.

Severity of negative esophageal pressure (Pes) and apnea hypopnea index (AHI) were investigated in 34 patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). The OSAHS patients were diagnostically classified as having obstructive sleep apnea syndrome (OSAS) or upper airway resistance syndrome (UARS). Diagnosis of OSAS was based on an AHI of more than 5, and that of UARS on an AHI of less than 5, EEG arousals which were associated with apnea, hypopnea and/or respiratory effort occurring more than 10 times per hour, and daytime sleepiness. Negative Pes was represented by the greatest peak (NPes Max) and the number of increased (more than 13.5 cmH2O) episodes per hour (NPesI13.5). There was no significant correlation between the AHI and Pes indices, but NPes Max and NPesI13.5 showed significant correlation (p<0.01). NPes Max and NPesI13.5 showed no significant differences among the severe OSAS (AHI>50; 8 cases), moderate OSAS (50>AHI>15; 10 cases), mild OSAS (15>AHI>5; 9 cases) and UARS (7 cases) groups. We conclude that AHI does not reflect the severity of the increase in negative Pes, which is an important aspect of the pathophysiology of OSAHS. Assessment of OSAHS based on AHI alone may therefore underestimate the risk of increased negative Pes in cases with reduced AHI.

A frequent deletion of chromosome 5q21 in advanced small cell and non-small cell carcinoma of the lung.

We have examined the deletion of the long arm of chromosome 5 (5q) in 59 cases of advanced lung cancer [39 cases of small cell lung cancer (SCLC), 20 cases of non-SCLC] using 12 restriction fragment length polymorphism markers on 5q. Of 59 lung cancer cases, 48 (81%) exhibited deletion at any portion of the 5q locus (loci). Such a high frequency of 5q deletion has not been reported in surgically resectable non-SCLC. One SCLC case showed a 5q deletion only in metastatic sites but not in the primary cancer. These data suggest that the inactivation of putative tumor-suppressor gene(s) on 5q may be a late event in the progression of lung cancer. There was no significant difference in frequency of 5q deletion between SCLC and non-SCLC. Compared to non-SCLC, however, SCLC usually showed widespread deletion on 5q. While the most frequent target region was estimated to be about 3-5 megabases at 5q21 around the adenomatous polyposis coli (APC) gene locus, some cases showed more telomeric deletion (5q33-35), suggesting that there are at least two different tumor-suppressor genes on 5q associated with the progression of lung cancer.

Detailed deletion mapping of the short arm of chromosome 3 in small cell and non-small cell carcinoma of the lung.

We constructed a detailed deletion map of the short arm of chromosome 3 (3p) for 55 lung cancer cases by using 17 restriction fragment length polymorphism (RFLP) probes. Initially, we examined 40 small cell lung cancer (SCLC) cases and found three regions of deletion at 3p25-26, 3p21.3 and 3p14-cen, suggesting the possibility of at least three different tumor-suppressor genes on 3p. In order to obtain more detailed deletion area, and to compare the pattern of 3p deletion, we also examined 15 non-small cell lung cancer (NSCLC) cases. Compared to NSCLC cases, most of SCLC cases have widespread deletion on 3p, suggesting multiple tumor-suppressor genes on 3p may be inactivated in this type of cancer. In 3p21.3 area, minimum overlapping area of deletion lays between two probes which are close to each other. These data will be useful to isolate the putative tumor-suppressor genes located on the chromosome 3p.

Generation of a small cell lung cancer variant resistant to lymphokine-activated killer (LAK) cells: association with resistance to a LAK cell-derived, cytostatic factor.

Cells of OS2-RA, a human small cell lung cancer line sensitive to lymphokine-activated killer (LAK) cells, were repeatedly cocultured with human LAK cells. Fourteen cycles of the coculture produced a variant, termed OS2-RA-R, capable of growing successfully in the presence of LAK cells. OS2-RA-R showed a moderate resistance to lysis by LAK cells in 4-h 51Cr release assays. OS2-RA-R acted positively as a cold target for lysis of OS2-RA by LAK cells, suggesting no loss of the binding site for LAK cells on the cell surface of the variant. On the other hand, LAK cells were shown to produce a factor capable of suppressing the proliferation of OS2-RA and certain other cell lines but not lymphocytes. Interestingly, OS2-RA-R exhibited a substantial resistance to the cytostatic activity of LAK cell supernatants. The cytostatic factor, eluted at the 57-kDa fraction in gel filtration, showed no activity of interleukin 1, gamma-interferon, transforming growth factor beta, or tumor necrosis factor. These results suggest that LAK cells exhibit antitumor activity through not only rapid cytolysis but also slow-acting cytokine production, and the successful growth of OS2-RA-R in a coculture with LAK cells is the result of acquiring resistance to these two different LAK cell phenomena.