We studied the influences of chronic tobacco exposure on aging and oxidant-antioxidant balance in two different strains of mice, hitherto called SAM (senescence-accelerated mice). One is a senescence-prone strain, "SAM-P/2," and another is a senescence-resistant strain, "SAM-R/1." We used 100 male mice--20 young (12 weeks of age) mice and 30 mature (24 weeks of age) mice from each strain. Half of each series were housed in a Hamburg II machine and exposed to tobacco smoke inhalation for five weeks. The result was that fewer of the mature SAM-P/2 survived compared with the mature SAM-R/1 after chronic tobacco inhalation. The grading of senility in the mature SAM-P/2 was also significantly higher than that in the mature SAM-R/1. The reduction of glutathione contents of blood and liver after tobacco exposure in the mature SAM-P/2 was greater than that in the young SAM-P/2 and the mature SAM-R/1. Moreover, oxygen radical generation of total blood cells stimulated by phorbol-myristate-acetate or opsonized zymosan showed a greater increase in the mature SAM-P/2 compared to the young SAM-P/2 and the mature SAM-R/1. These results indicate that the senescence-prone strain (SAM-P/2) was more susceptible to tobacco smoke exposure than the resistant strain (SAM-R/1). The impaired oxidant-antioxidant balance in the SAM-P/2 may therefore contribute to the process of senescence acceleration.

Aging↗

PubMedDate not supplied

Bilateral large peripapillary venous and arterial loops.

BACKGROUND: Peripapillary loops of venous origin are extremely rare. CASE: A 55-year-old woman was referred to us for further examination of peripapillary vascular abnormalities. OBSERVATIONS: Fundus examination and fluorescein angiography clearly showed a venous and an arterial peripapillary loop in both her right and left fundi. The venous loop in the right eye was in a large hairpin configuration, extending into the retina about 1 disc diameter from the optic disc. Fluorescein angiography in the left eye revealed slow and irregular filling of dye into a venous loop that showed stasis of the bloodstream through the loop. Various retinal vascular abnormalities, including cilioretinal artery and triple branching of the retinal vein were also observed. CONCLUSION: The findings in this case of bilateral peripapillary venous and arterial loops and unilateral trifurcation of retinal vein suggest that there could be an association in the other retinal abnormalities. Periodic follow-up examinations seem necessary.

Coloring Agents↗

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An in vitro screening system for characterizing the cleft palate-inducing potential of chemicals and underlying mechanisms.

An in vitro organ culture system with developing mouse palates was improved to characterize the cleft palate (CP)-inducing potential of chemicals and underlying mechanisms. Palatal explants collected from gestation day 12 mouse fetuses were cultured with various concentrations of teratogens and examined for palatal development after 48 and 72 h of culture to assess effects of the chemicals on growth and/or fusion of palatal shelves. When the explants were exposed to diphenylhydantoin or 5-fluorouracil, palatal growth was inhibited in a concentration-dependent manner at 48 h. Suppression of the expression of proliferative cell nuclear antigen revealed poor cell proliferation. At 72 h, the incidence of explants with CP was significantly increased in the high-dose groups, suggesting that CP induction is mainly attributable to inhibition of palatal growth. By contrast, retinoic acid and hydrocortisone significantly lowered the rates of fused palates at 72 h in all treated groups, while they exhibited no effects on palatal growth at 48 h even at the highest concentration. Because no apoptosis was found in the epithelial cells at the tip of these palates, these chemicals are suggested to inhibit palatal fusion process by preventing apoptosis.

Animals↗

PubMedDate not supplied

Polydactyly lethal: a new mutant spontaneously occurring in the FPL strain of rats.

A new mutant gene that causes preaxial polydactyly in the hindlimbs was found in the strain of rats with fused pulmonary lobes (fpl). Genetic analysis has revealed that the new mutation is inherited as an autosomal recessive trait and is not closely linked with the fpl gene. Since homozygous mutants die within the first 2 days after birth, the mutant gene was named polydactyly lethal, gene symbol pl. A test for allelism between the pl gene and another gene, pd, which also causes preaxial duplication anomalies, showed no allelism between these two genes. Skeletal examination revealed that all pl/pl newborns had thickening and/or bifurcation of tarsal I and metatarsal I, as well as duplication of the proximal and distal phalanges of digit I in the hindlimbs. In some cases, phalangeal duplication or bifurcation in digit I with thickening of metacarpal I was also found in the forelimbs, although extra forelimb digits were not detected externally. The pl/pl newborns showed hunchback-like abnormal posture externally and had several associated vertebral abnormalities in varying degrees, i.e., kyphosis, scoliosis, splitting of the thoracic vertebral bodies, and fusion of the lumbar vertebral bodies. No major malformations were seen in the visceral organs. The cause of neonatal deaths has not yet been determined.

Alleles↗

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Influences of cisplatin combination chemotherapy on oxygen radical generation by blood in elderly and adult patients with lung cancer.

Oxygen radical generation by blood cells before and after chemotherapy was investigated in 16 elderly (72.8 +/- 1.0 years) and 14 adult (45.0 +/- 2.4 years) patients with lung cancer, using a lucigenin-dependent chemiluminescence method. The oxygen radical generation by 100 microliters of blood before chemotherapy in the elderly and the adults was 3,784 +/- 123 and 3,969 +/- 125 chemiluminescence (CL), respectively. The value decreased gradually and reached a nadir at 2 weeks after therapy (elderly: 1,090 +/- 37; adult: 1,114 +/- 38 CL). Peripheral leukocyte counts also reached a nadir then: 1,308 +/- 140 and 1,288 +/- 44/mm3, respectively. However, the oxygen-radical-generating activity per leukocyte was not different before and after the therapy (elderly: 0.94 +/- 0.14 CL before to 0.83 +/- 0.09 CL after; adult: 0.97 +/- 0.13 CL before to 0.87 +/- 0.10 CL after). These results indicate that a decrease in oxygen radical generation by blood following chemotherapy is mainly due to a decrease in the number of polymorphonuclear neutrophils both in elderly and adult patients.

Adenocarcinoma↗

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Significant survival benefit to patients with advanced non-small-cell lung cancer from treatment with clarithromycin.

We carried out a randomized study of 49 consecutive patients with unresectable primary lung cancer to determine whether clarithromycin (CAM), a 14-membered ring macrolide, can improve outcome. A total of 49 patients (42 patients with non-small-cell lung cancer and 7 patients with small-cell lung cancer) had received prior chemotherapy, radiotherapy or both during their hospital stay. They were randomly allocated into two study groups on the first visit after discharge: 25 patients (22 patients with non-small-cell lung cancer, 3 patients with small-cell lung cancer) were assigned to receive CAM (400 mg/day, orally), and 24 patients (20 patients with non-small-cell lung cancer, 4 patients with small-cell lung cancer) did not receive CAM. CAM treatment after randomization was open and the treatment was to be continued as long as the patients could tolerate CAM. There was no significant difference in the median survival time for small-cell lung cancer between the CAM group and the non-CAM group. However, CAM treatment significantly increased the median survival time for non-small-cell lung cancer patients, the median survival for the CAM group was 535 days and that for the non-CAM group was 277 days. Analyses of prognostic factors showed that only treatment with CAM was predictive of longer survival for non-small-cell lung cancer, and other tested covariates had no effects on the prognosis. There were no remarkable side effects observed in the CAM group throughout treatment. We conclude that long-term treatment using CAM is beneficial for unresectable non-small-cell lung cancer patients and that it can increase the median survival of patients with advanced disease.

Aged↗

PubMedDate not supplied

[Analysis of nocturnal disturbed breathing in the elderly using desaturation index].

This study was conducted to examine the nocturnal ventilatory parameters and gas exchange in the elderly with nocturnal disturbed breathing. In order to facilitate analysis of ventilatory parameters with minimum manpower, we developed an unattended continuous nocturnal monitoring system for ventilation and arterial oxygen saturation. Using this system, nocturnal ventilatory parameters and gas exchange were investigated in our geriatric ward. We investigated 30 elderly subjects aged between 65 and 94 (mean age 77.8 +/- 6.5 years, male; female = 15:15). The subjects were free of severe cardiovascular and cerebrovascular disorders, and underwent 10 hours of continuous monitoring of ventilation and arterial oxygen saturation (SaO2). Number of significant desaturation (SDS; desaturation greater than 4% in SaO2 from the baseline value) and desaturation index (DI; sigma SDS(%) x duration (hour)) were calculated using the same system. The number of apnea episodes significantly correlated with DI and the number of SDS. DI also significantly correlated with lowest SaO2, while the number of SDS and the number of apneas were not found to be correlated with lowest SaO2. The number of SDS and the number of apnea episodes did not correlated with lowest SaO2. From the view point of gas exchange during the night, newly introduced DI is more comprehensive parameter when compared with the number of apneas or SDS. Subjects with a DI of over 0.5 were assigned to the group A (n = 8, mean age = 77.8) and the remaining subjects were assigned to group B (n = 22, mean age = 77.8). We compared the group A with the group B regarding nocturnal ventilatory parameters and SaO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMedDate not supplied

The impact of FK506 on graft coronary disease of rat cardiac allograft--a comparison with cyclosporine.

We studied the impact of FK506, a potent immunosuppressant, on graft coronary disease and graft-infiltrating lymphocyte subset after rat heart transplantation. Fisher rat heart grafts transplanted into Lewis rat recipients were divided into three groups: control (n = 7), rats treated with FK506 at a dose of 0.32 mg/kg/day intramuscularly (n = 7), and rats treated with cyclosporine at a dose of 10 mg/kg/day intramuscularly (n = 7). Grafts were removed on day 71 in the treated groups and on rejection in the control group. We blindly scored graft rejection and graft coronary disease on a scale of 0 to 4. Graft-infiltrating lymphocytes were investigated by flow-cytometric analysis with the following monoclonal antibodies: W3/25, anti-helper T lymphocyte; OX8, antisuppressor and cytotoxic T lymphocyte; and OX39, antiinterleukin-2 receptor. No difference of graft rejection was found between the two treated groups (FK506 1.66 +/- 0.49 versus cyclosporine 1.45 +/- 0.37), but the FK506 group showed severe graft coronary disease (FK506 2.14 +/- 0.82 versus cyclosporine 0.78 +/- 0.17; p less than 0.01) in this model. In flow-cytometric analysis, we found an increased proportion of OX8-positive lymphocytes (FK506 25.7 +/- 6.4 versus cyclosporine 4.9 +/- 2.4, p less than 0.01). These results suggest that suppression of cytotoxic T lymphocytes may be involved in graft coronary disease.

Animals↗