Thinning of fetal pulmonary arterial wall and postnatal remodelling: Ultrastructural studies on the respiratory unit arteries of the pig

Summary Adaptation to extra-uterine life and postnatal remodelling of intra-acinar arteries was followed in 34 Large White pigs, from birth to adult life, applying morphometry to light and electronmicroscopic studies. After birth, percentage wall thickness decreased rapidly due to a reduction in overlap of adjacent smooth muscle cells and an increase in smooth muscle cell surface area/volume ratio, (p<0.01 at 12 h), without a reduction in the volume density of smooth muscle cells. Smooth muscle cells appeared immature at birth and synthetic rather than contractile organelles predominated. Between 3 weeks and 6 months myofilament volume density doubled (p< 0.0001). At all ages, pericytes, intermediate and smooth muscle cells showed similar volume densities of contractile and synthetic organelles. Thus, the high fetal pulmonary vascular resistance appeared to be due to the shape and arrangement of smooth muscle and other contractile cells within the vessel wall, rather than an excessive contractility of these cells. After birth rapid remodelling of arterial wall structure achieved a reduction in wall thickness by 30 min, continuing during the first week of life. After 3 weeks, remodelling involved an increase in wall thickness, connective tissue deposition with more collagen than elastin (p<0.0001), and smooth muscle cell differentiation.     

HER2 protein expression and gene amplification in androgen-independent prostate cancer

The role of the HER2 receptor remains uncertain in the pathogenesis and progression of human prostate cancer. Previous studies have reported widely divergent rates for HER2 expression in primary prostate tumors, probably owing to significant methodologic differences in the studies. Few data exist about the frequency of HER2 protein overexpression and gene amplification in androgen-independent prostate cancer (AIPC), although recent xenograft models suggest HER2 expression may be up-regulated in the transition from androgen-dependent to androgen-independent disease. We studied the role of HER2 protein in AIPC by immunohistochemical and fluorescence in situ hybridization (FISH) analyses on AIPC specimens using well-characterized and validated reagents. Fourteen (36%) of 39 specimens expressed HER2; however, only 2 (5%) had moderate (2+) expression, and 2 (5%) had high-level (3+) expression. Two (6%) of 36 specimens had gene amplification by FISH. These data suggest that HER2 protein overexpression and gene amplification are relatively uncommon in AIPC.     

Ultrastructural studies of interactions of B16 melanoma cells and normal mouse skin fibroblasts in the three-dimensional collagen gels in vitro

In the in vivo system, cancer metastasis is a complex multi-step process. We have utilized an in vitro three-dimensional system to study the initial stages of tumour cell invasion. In this communication, the sequence of events in interactions between B16 melanoma cells and normal mouse skin fibroblasts are described. It is proposed that tumour cells produce a "retractive factor" which induces the underlying fibroblasts to retract so as to facilitate invasion and metastasis.     

Diabetic retinopathy and lipid abnormalities

The relationship of serum lipid levels and diabetic retinopathy has interested clinicians for several decades. Data from both a population-based study of diabetic retinopathy and a controlled, randomized trial of laser photocoagulation and aspirin treatment in diabetic retinopathy have provided further information regarding the importance of the role of serum lipids in patients with elevated serum lipid levels and diabetic retinopathy. Retinal hard exudate, which is accompanied by macular edema, is associated with elevated serum lipid levels. Although the data are observational, visual loss is likely to be associated with retinal hard exudate and serum lipid abnormalities. These relationships are evaluated in the analyses of the data from the Early Treatment Diabetic Retinopathy Study.     

Nutritional supplement use and age-related macular degeneration

Age-related macular degeneration is one of the leading causes of visual loss among people aged 65 years or older. The causes and factors associated with the progression of age-related macular degeneration are unknown presently. Basic research and epidemiologic data support the hypotheses that higher levels of antioxidant vitamins and minerals may protect the eye from the development of age-related macular degeneration. For this reason and also because of the lack of effective treatment for most cases of age-related macular degeneration, nutritional supplements with antioxidants have emerged as possible therapy for age-related macular degeneration. Nutritional supplements are not proven therapy for age-related macular degeneration. The potential beneficial effects and adverse side effects of the nutritional supplements have not yet been fully evaluated in carefully conducted clinical trials. Several randomized placebo-controlled clinical trials are presently underway. Results of these studies will provide important data to clarify the potential beneficial and adverse effects of such treatment. Until these results are available, it would be premature to make recommendations in favor of vitamin or mineral supplements.     

Prospective cohort study of antioxidant vitamin supplement use and the risk of age-related maculopathy

In a prospective cohort study, the authors examined whether self-selection for antioxidant vitamin supplement use affects the incidence of age-related maculopathy. The study population consisted of 21,120 US male physician participants in the Physicians' Health Study I who did not have a diagnosis of age-related maculopathy at baseline (1982). During an average of 12.5 person-years of follow-up, a total of 279 incident cases of age-related maculopathy with vision loss to 20/30 or worse were confirmed by medical record review. In multivariate analysis, as compared with nonusers of supplements, persons who used vitamin E supplements had a possible but nonsignificant 13% reduced risk of age-related maculopathy (relative risk = 0.87, 95 percent confidence interval (CI) 0.53-1.43), while users of multivitamins had a possible but nonsignificant 10% reduced risk (relative risk = 0.90, 95% CI 0.68-1.19). Users of vitamin C supplements had a relative risk of 1.03 (95% CI 0.71-1.50). These observational data suggest that among persons who self-select for supplemental use of antioxidant vitamin C or E or multivitamins, large reductions in the risk of age-related maculopathy are unlikely. Randomized trial data are accumulating to enable reliable detection of the existence of more plausible small-to-moderate benefits of these agents alone and in combination on age-related maculopathy.     

Calcium oxalate urolithiasis in cats

Urolithiasis has long been recognized as a cause of irritative voiding in cats. Before the late 1980s, sterile struvite was the most common urolith; today, however, 40% of feline uroliths are of calcium oxalate. This change may be partly attributable to the change to urine-acidifying, magnesium-restricted diets that were introduced to reduce the formation of struvite. However, it is possible that the diet modifications made by cat food manufacturers simply exposed a population of cats predisposed to calcium oxalate stone formation. Urolithiasis in cats appears to be diet sensitive rather than diet induced. As in humans, water is crucial in the prevention and treatment of feline stones.