Isozyme phenotypes of polyoma virus tumors in mice

Isozyme profiles for 32 enzyme systems were studied in tumors induced by two strains of polyoma virus (2PTA and LID1), in two conventional mouse strains (C3H/BiDa and NIH), and in athymic (nude) mice of two genetic backgrounds (C3H/Hes nu/nu and NIH nu/nu). Tumors studied were: primary and transplant passages of salivary gland tumors (127); primary thymic epithelial tumors (12); primary subcutaneous sarcomas (6); primary hair follicle tumors (5); primary and transplant passages of mammary tumors (18); primary ameloblastomas (3); and primary renal medullary sarcomas (3). Regardless of mouse strain or virus strain, the isozyme arrays were highly constant and unique for each tumor histotype with the exception of salivary and mammary tumors, which shared a single profile differing from that of each of the other histotype-associated profiles. Other tumor types could be distinguished from each other and from the salivary-mammary tumor pair by as few as five isozymes: glycerol-3-phosphate dehydrogenase; glyceraldehydephosphate dehydrogenase; lactate dehydrogenase; sorbitol dehydrogenase; and alkaline phosphatase. Twelve nonpolyoma mammary tumors and their passages from mouse mammary tumor virus-expressed C3H/Hes nu/+ mice were analyzed for the same enzymes; variations in activity and isozyme profiles were found for ten enzyme systems. Three spontaneous salivary myoepitheliomas in BALB/c mice were also analyzed; two different lactate dehydrogenase profiles were observed, and all three tumors lacked the placental alkaline phosphatase present in polyoma virus-induced salivary tumors. Uniformity of isozyme phenotype may be characteristic of DNA virus transformation of cells in a particular differentiative state. This uniformity does not appear to occur in mouse mammary tumor virus-associated tumors, spontaneous tumors, and, according to the literature, chemically induced tumors.     

Point mutations in polypeptide VP1 of foot-and-mouth disease virus affect mouse virulence and BHK21 cell pathogenicity

Virus produced in the first four days after infection of a BHK21 culture was shown to differ from that produced later in the infection. The early virus caused large plaques in IB-RS-2 cell sheets, had a slow cytopathic effect in BHK21 cultures and showed a high virulence for suckling mice. In contrast, the late virus caused small plaques, was rapid in its cytopathic effect and was of low virulence for mice. Comparison between one clone each of the early and late virus showed that no change in immunogenic specificity had taken place, but that charge changes had occurred both in VP3 and in the large trypsin-resistant fragment of VP1. The early, large plaquing clone gave rise spontaneously to small plaquing virus during the destructive phase of a single passage in BHK21 cultures. Conversely, the late, small plaquing clone gave rise to large plaquing virus after a single passage in mice. Each new virus was cloned and it was shown that they differed in VP1. This indicated that missense mutations in the genome coding for the trypsin resistant fragment of VP1 were responsible for the biological changes observed.     

Digoxin biotransformation

Serum digoxin and metabolites were assayed in plasma and urine by HPLC in 10 dialysis-dependent patients with end-stage renal failure (group I) and in five patients with comparatively normal renal function (group II) after ingestion of 150 muCi 3H-digoxin-12 alpha. Thirteen patients were on maintenance digoxin therapy and were at steady state. Metabolites found regularly but usually in small amounts, were 3 beta-digoxigenin and its mono- and bis-digitoxosides, and 3-keto and 3 alpha(epi)-digoxigenin. Quantitatively the most abundant metabolites were polar and averaged 26% (7 to 76) of the radioactivity in plasma 6 hr after drug, and 60% (11 to 88) for digoxin for all 15 patients. Neither values between group I and II for the polar metabolites nor digoxin differed significantly. The metabolites reacted with antibody to digoxin to varying degrees and may make up an important component of the serum digoxin concentration when determined by standard radioimmunoassay. In some patients, digoxin undergoes extensive biotransformation, mainly, we suggest by hydrolysis, oxidation, epimerization, and conjugation to polar end-metabolites.     

Capacity of mammary fat pads of adult C3H/HeMs mice to interact morphogenetically with fetal mammary epithelium.

When rudimentary mammary epithelium from 13- to 17-day female C3H/HeMs fetuses was transplanted into gland-free mammary fat pads of 3-week-old mice, organogenetic development of the grafts occurred, resembling that seen in normal mammary gland morphogenesis. Initial developmental growth did not require the reproductive hormones. Mammary fat pads of juvenile (3-wk-old), young adult (8- to 12-wk-old), and fully matured (40-wk-old) females had equal ability to interact morphogenetically with fetal mammary epithelium. Fetal pulmonary, pancreatic, and salivary gland epithella showed no morphogenetic response within adult mammary fat. An exception was rudimentary hair follicle epithellum, which underwent extensive development toward hair follicles within mammary fat. Mammary glands that developed from rudimentary mammary epithellum transplanted into gland-free fat pads underwent morphologic changes characteristic of lactation when the hosts bore young.     

Chronic actinic dermatitis in the elderly: recognition and treatment

Chronic actinic dermatitis is a condition involving abnormal cutaneous photosensitivity to UV and, often, visible wavelengths. It is rare, but more common in the elderly than in younger populations, with an estimated prevalence of one in 2000 in the > or = 75-year-old population in Tayside, Dundee, Scotland. It usually presents as a dermatitis that maximally, but not exclusively, affects photo-exposed skin. Investigation to confirm the diagnosis and guide management includes phototesting and patch testing. The mainstay of treatment is education about the condition and advice on sunlight and allergen avoidance. Topical corticosteroids and emollients are always required, at least intermittently, and it is sometimes necessary to resort to systemic immunosuppression, usually with corticosteroids or azathioprine.     

Improved mitochondrial bioenergetics by anesthetic preconditioning during and after 2 hours of 27 degrees C ischemia in isolated hearts

We examined if sevoflurane given before cold ischemia of intact hearts (anesthetic preconditioning, APC) affords additional protection by further improving mitochondrial energy balance and if this is abolished by a mitochondrial KATP blocker. NADH and FAD fluorescence was measured within the left ventricular wall of 5 groups of isolated guinea pig hearts: (1) hypothermia alone; (2) hypothermia+ischemia; (3) APC (4.1% sevoflurane)+cold ischemia; (4) 5-HD+cold ischemia, and (5) APC+5-HD+cold ischemia. Hearts were exposed to sevoflurane for 15 minutes followed by 15 minutes of washout at 37 degrees C before cooling, 2 hours of 27 degrees C ischemia, and 2 hours of 37 degrees C reperfusion. The KATP channel inhibitor 5-HD was perfused before and after sevoflurane. Ischemia caused a rapid increase in NADH and a decrease in FAD that waned over 2 hours. Warm reperfusion led to a decrease in NADH and an increase in FAD. APC attenuated the changes in NADH and FAD and further improved postischemic function and reduced infarct size. 5-HD blocked the cardioprotective effects of APC but not APC-induced alterations of NADH and FAD. Thus, APC improves redox balance and has additive cardioprotective effects with mild hypothermic ischemia. 5-HD blocks APC-induced cardioprotective effects but not improvements in mitochondrial bioenergetics. This suggests that mediation of protection by KATP channel opening during cold ischemia and reperfusion is downstream from the APC-induced improvement in redox state or that these changes in redox state are not attenuated by KATP channel antagonism.     

Congenital deficiency of the tibia

The late results of treatment of 24 legs in 21 children with congenital deficiency of the tibia are presented. A new classification is proposed which correlates well with recommendations for treatment and with the final functional result. Three types of deficiency were recognised: Type I, total absence of the tibia; Type II, distal absence; Type III, distal deficiency with tibiofibular diastasis. The early radiographic appearances, the functional status of the quadriceps and the severity of flexion contracture of the knee were important factors in the selection of the operations likely to give the best function.     

The photocarcinogenic risk of narrowband UVB (TL-01) phototherapy: early follow-up data

BACKGROUND: Limited information is available on the carcinogenic risk associated with narrowband TL-01 UVB phototherapy in humans. OBJECTIVES: To determine the skin cancer incidence in a population treated with TL-01 phototherapy. PATIENTS AND METHODS: All TL-01-treated patients were identified from the departmental computerized database. Patients with malignant melanoma (MM), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) were identified by record linkage with the Scottish Cancer Registry. The incidence of each was compared with the normal Scottish population matched for age and sex. RESULTS: Data were obtained from 1908 patients. The median follow-up duration was 4 years (range 0.04-13). The median cumulative number of TL-01 treatments and dose were 23 (1-199) and 13 337 (30-284 415) mJ cm(-2), respectively. No increased incidence of SCC or MM was observed. Ten patients developed BCC compared with an expected 4.7 in the Scottish population [standardized rate ratio 213 (95% confidence interval 102-391); P < 0.05]. CONCLUSIONS: A small but significant increase of BCC was detected in the TL-01 group. This could be explained by a number of factors, including ascertainment bias. To determine the true carcinogenic risk of TL-01 phototherapy, longer follow-up is essential.     

Does narrow‐band ultraviolet B phototherapy work in atopic dermatitis through a local or a systemic effect?

The likely mechanisms of action of narrow-band ultraviolet B (NB-UVB) in atopic dermatitis are several. We attempted, in a 12 patient prospective intraindividually controlled study, to determine whether the effect of NB-UVB in atopic dermatitis is primarily through systemic or local effects. Change in observer-assessed severity of patches of dermatitis covered during each whole-body NB-UVB treatment was compared with change in uncovered neighbouring patches. We found great variation between patients in responses. Only in two (of 12) patients was there a large difference between directly exposed and covered patch dermatitis severity. We suspect that the balance of local and systemic effects important in determining response to NB-UVB in atopic dermatitis varies from patient to patient. This study did not conclusively answer our original question, but did show that in some patients localized effects of NB-UVB are important.