Potentiation of vincristine and actinomycin D by a new synthetic imidazole anti-tumor agent YM534 active against human cancer cells and multidrug-resistant cells

Ethyl 6-p-5-(l-imidazolyl) pentyloxyphenoxy-2, 2-dimethylhexanoate hydrochloride (YM534) is a new synthetic anti-tumor compound. Combinations of YM534 with other anti-cancer agents were examined to ascertain whether YM534 potentiated other anti-cancer agents against the KB cell line and its multidrug-resistant counterpart, VJ-300. YM534 potentiated the cytotoxic action of vincristine and actinomycin D about 2-fold against KB cells, but not those of daunomycin and adriamycin. By contrast, YM534 only slightly reversed drug-resistance to adriamycin and daunomycin in VJ-300 while it reversed 5-fold vincristine resistance and 60-fold actinomycin D resistance in VJ-300. The reversal effect of YM534 on actinomycin D and vincristine-resistance in VJ-300 cells appeared to be due to enhanced accumulation of [3H] actinomycin D and [3H] vincristine in VJ-300 cells by YM534. YM534 inhibited efflux of actinomycin D and vincristine from VJ-300 cells, and it also enhanced cellular uptake of these anti-cancer agents. YM534 enhanced cellular accumulation of both actinomycin D and vincristine in the sensitive KB cells. YM534 is thus a unique anti-cancer agent since combinations of other anti-cancer agents with YM534 are expected to augment anti-tumor activity of them. By contrast, YM212, a carboxy analog of YM534, had much less activity to potentiate vincristine and actinomycin D). YM534 at 100-1000 microM almost completely inhibited the photoaffinity labeling of [3H] azidopine to the 170-kD P-glycoprotein of VJ-300 cell membranes, but YM212 showed much less inhibitory action on the photoaffinity labeling. YM534 could also inhibit the photoaffinity labeling of deglycosylated P-glycoprotein.     

Limited vertical skin incision for median sternotomy.

The cosmetic deformity of the vertical skin incision for median sternotomy was decreased by using a mechanical traction system to increase exposure at the superior margin of a shorter wound. The limited vertical skin incision did not impede technical surgical maneuvers and produced a scar that was more acceptable than submammary incision or right anterior thoracotomy. The limited skin incision is especially useful in young women with congenital heart disease.     

Uveitis associated with human T-cell lymphotropic virus type I.

Seroepidemiologic, clinical, and virologic studies were performed to determine whether human T-cell lymphotropic virus type I was closely associated with uveitis in two hospitals. One hospital was in an endemic area of the virus (Miyakonojo, Miyazaki) and the other hospital was in a less endemic area (Kurume). In the endemic area, the seroprevalence of the virus in patients with uveitis without defined causes (35.4%, 62 of 175 patients) was significantly higher than that in patients with nonuveitic ocular diseases (16.1%, 42 of 261 patients), or in patients with uveitis with defined causes (10.3%, eight of 78 patients). The seroprevalence in younger patients (20 to 49 years of age) with uveitis without defined causes in the area was 44.8% (30 of 67 patients), whereas it was only 9.3% (ten of 107 patients) in the other two groups. A similar observation was recorded even in the less endemic area (Kurume). Because the seroprevalence of the virus in the general population is known to be low in younger patients and to increase with age, these findings were interpreted to indicate that the association of human T-cell lymphotropic virus type I with uveitis was significant. Most patients, particularly those aged 20 through 49 years, had an intermediate uveitis characterized by a moderate inflammation in the vitreous body accompanied by an iritis and retinal vasculitis. The ocular symptoms in the patients differed from those of other types of uveitis common in Japan (Beh?et's disease, Vogt-Koyanagi-Harada's disease, and toxoplasmosis, for example).(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanism of ethanol-induced bronchoconstriction in Japanese asthmatic patients]

Acute ingestion of alcoholic beverages causes no changes in the expiratory airflow rates of most Occidental asthmatic patients. However, asthmatic symptoms are worsened after drinking small amounts of alcohol in Japanese asthmatic patients. Our laboratory results showed that the ingestion of pure ethanol caused a fall in FEV1.0 in about half of the Japanese asthmatic patients tested. The mechanism of ethanol-induced bronchoconstriction remains unclear. In order to investigate this mechanism, we performed oral-provocation tests with 10% ethanol in vivo, and leukocyte histamine release assay induced by ethanol and acetaldehyde in vitro. 55% of asthmatics showed a significant fall in FEV1.0 after ingestion of 10% ethanol (responder). There was no difference in the rise of blood ethanol concentration between the responder group and non-responder group. Acetaldehyde and histamine concentration in the responder group were significantly higher than in the non-responder group. Leukocyte histamine release assay showed that acetaldehyde (2 microM-100 microM) caused dose-dependent histamine release, whereas, ethanol (2 mM-100 mM) had no effect on histamine release. Our data indicate that histamine release from mast cells (or basophils) caused by acetaldehyde may play an important role in ethanol-induced bronchoconstriction. This is the first report on the mechanism of ethanol-induced bronchoconstriction in Japanese asthmatic patients.     

HTLV-I uveitis: a distinct clinical entity caused by HTLV-I.

Seroepidemiological, clinical and virological studies were carried out in an HTLV-I endemic area to find out if HTLV-I caused an intraocular inflammatory disorder, uveitis. The seroprevalence in patients with uveitis without defined etiologies (62/175, 35.4%) was significantly higher than that in patients with non-uveitic ocular diseases (42/261, 16.1%) or in patients with uveitis with defined etiologies (8/78, 10.3%). Moreover, the seroprevalence in young adults (20-49 years) with uveitis without defined etiologies was 30/67 (44.8%), whereas it was only 10/107 (9.3%) in the other two groups. The uveitis in HTLV-I carriers was characterized clinically by a moderate inflammation of the vitreous body accompanied by a mild iritis and retinal vasculitis. The proviral DNA of HTLV-I was detected by polymerase chain reaction from the inflammatory cells in the anterior chamber in 9 out of 9 seropositive patients with the uveitis, but not in any of the tested patients with other types of uveitis. These data, thus, indicate that HTLV-I causes a specific type of intraocular inflammation, uveitis.     

A study on the hemodialysis period following cadaveric kidney transplantation--a comparison between two centers sharing cadaver donor kidney pairs

To study the hemodialysis period following cadaveric renal transplantation, we reviewed 18 consecutive cadaver donor kidney pairs of which one kidney was transplanted at Shiga University of Medical Science (SUMS) while the contralateral kidney was transplanted at Kyoto Prefectural Medical University (KPMU) between January 1983 and September 1988. Of these 18 pairs, graft function was satisfactory and the recipient was free from hemodialysis in 13 pairs. However, the postoperative hemodialysis periods were different between the two centers. To clarify the factors causing this difference, recipient factors, such as age, HLA matching, total ischemic time of the graft (TIT), immunosuppression, onset of diuresis and postoperative complications were studied. There were no significant differences in age, HLA matching, or immunosuppression. TIT of cases at SUMS was significantly longer than that of cases at KPMU. The postoperative hemodialysis period at SUMS was 25.8 days and that at KPMU was 17.8 days, however, the difference was not statistically significant. The results of this study indicate that TIT seems to be a major factor relating to delayed graft function in cadaveric renal transplantation.     

A case report of mitral valve regurgitation due to the infective endocarditis associated with the straight back syndrome

A 54 year-old man was admitted to our hospital with a compliant of high fever following the dental treatment. He had the straight thoracic spine with absence of physiological kyphosis. Blood culture was positive for Streptococcus sanguis I. Echocardiography revealed the mitral valve regurgitation with some vegetation at the ruptured chordae tendinae of the posterior leaflet. The operation was performed after the sign of the inflammation was disappeared. We performed the mitral valve reconstruction following the Carpentier's technique. The half of the posterior leaflet was excised, and the annuloplasty and valvuloplasty was done with ease.     

Beneficial effect of diltiazem on pulmonary hypertension in a patient with Hughes-Stovin's syndrome]

A 54 year-old female who had a history of hemoptysis was admitted to our hospital because of dyspnea on effort. Pulmonary arterial pressure was elevated and pulmonary arteriography showed multiple pulmonary arterial aneurysms and occlusion of the left upper lobe pulmonary artery. Systolic pulmonary arterial pressure was 110 mmHg when measured by continuous wave Doppler echocardiography. From the clinical and angiographical findings, we diagnosed this patient as having Hughes-Stovin's syndrome (forme fruste). 30 mg of diltiazem per day was initially used, and 80 mg was used thereafter. After 2 months follow up of the medication with diltiazem, systolic pulmonary arterial pressure decreased from 110 mmHg to 61 mmHg and clinical symptoms improved dramatically.     

Mercury-selenium interaction in workers exposed to elemental mercury vapor

Mercury (Hg) and selenium (Se) levels were determined for erythrocytes, plasma and urine of 25 male and 29 female workers exposed to elemental mercury (Hgo) vapor. Interrelationship between the Hg levels and the Se levels was examined by the correlational analysis and the stepwise regression analysis. Indicators of Se status (erythrocyte Se levels, plasma Se levels and urinary Se levels) were closely intercorrelated; similarly, indicators of exposure to Hgo vapor (erythrocyte inorganic Hg levels, plasma Hg levels and urinary Hg levels) were significantly intercorrelated. Since plasma Hg level was one of the significant independent variables in determining the erythrocyte Se and plasma Se levels, Hgo vapor exposure was thought likely to influence the Se metabolism in workers. None of the Se status indicators were significant as determinants of the indicators of Hgo vapor exposure.