Melanocytes are not absent in lesional skin of long duration vitiligo

This paper provides evidence that melanocytes are still present in the depigmented epidermis of patients with vitiligo even after stable disease of 25 years' duration. Melanocyte cultures were successfully established from depigmented epidermal suction blister tissue of all 12 randomly selected patients and these cells produced melanin. Even under in vitro conditions, vacuolation of melanocytes was demonstrated in five patients with active disease, which was reversible upon exogenous addition of bovine catalase to the culture medium. Full skin biopsies from 17 patients with vitiligo, obtained from depigmented and normally pigmented areas, confirmed the involvement of melanocytes, keratinocytes, and Langerhans cells in this disorder. In addition, the presence of clustered and single pre-melanosomes in basal and supra-basal keratinocytes of lesional and normal epidermis, as well as the retention of single melanocytes in lesional epidermis, was demonstrated by light and electron microscopy. Upon topical application of a narrow band UVB-activated pseudocatalase, vacuolation, granulation, and dilatation of the endoplasmic reticulum completely recovered, but the ectopic pre-melanosome shedding remained. Taken together, these observations indicate that melanocytes are never completely absent in the depigmented epidermis and that these melanocytes can recover their functionality in vivo and in vitro upon the removal of hydrogen peroxide. Furthermore, this study supports the concept that vitiligo involves the entire epidermal unit in both depigmented and 'normal' pigmented skin.     

Protein A is the von Willebrand factor binding protein on Staphylococcus aureus

Endovascular infection is a highly critical complication of invasive Staphylococcus aureus disease. For colonization, staphylococci must first adhere to adhesive endovascular foci. Von Willebrand factor (vWF) is a large, multimeric glycoprotein mediating platelet adhesion at sites of endothelial damage. Earlier it was demonstrated that vWF binds to and promotes the surface adhesion of S. aureus, prompting this effort to identify the vWF adhesin. In Western ligand assays of S. aureus lysates, staphylococcal protein A (SPA) was recognized by purified vWF. Surface plasmon resonance demonstrated the binding of soluble vWF to immobilized recombinant protein A with a K(d) of 1.49 x 10(-8) mol/L. Using flow cytometry, the binding of fluorescein isothiocyanate-labeled vWF to S. aureus was found to be saturable and inhibitable by unlabeled vWF, antiprotein-A antibodies, or IgG. Isogenic Deltaspa::Tc(r) mutants were constructed by the insertion of a tetracycline resistance cassette into spa using allelic replacement, and it exhibited decreased binding of soluble vWF and decreased adhesion to vWF-adsorbed surfaces. The interaction was restored on complementation of the mutants with spa-containing plasmid pSPA7235. In conclusion, protein A confers interaction of S. aureus with soluble and immobilized vWF in a newly discovered function characterizing protein A as a novel member of the staphylococcal surface protein adhesin superfamily and suggesting its potential role in the pathogenesis of endovascular staphylococcal disease.     

Regulation of PKC delta expression by estrogen and rat placental lactogen-1 in luteinized rat ovarian granulosa cells

Protein kinase C (PKC) delta is dramatically upregulated in the corpus luteum in the second half of pregnancy in the rat. To gain insight into the hormonal regulation of PKC delta expression, studies were undertaken to analyze the regulation of PKC delta expression in a luteinized rat granulosa cell model. PKC delta protein expression was evaluated in luteinized granulosa cells, isolated from human (h)CG-treated immature female rats 7 h after the injection of an ovulatory dose of hCG and cultured up to 12 days. Cytochrome P450 cholesterol side chain cleavage enzyme expression was observed throughout the culture period, and a majority of the cells expressed steroidogenic acute regulatory protein and responded to rat placental lactogen (rPL)-1 by exhibiting hypertrophy, consistent with maintenance of the luteal phenotype. Both PKC delta protein and mRNA expression increased 3.5-4-fold with time of culture, and PKC delta mRNA expression could be eliminated by treatment of cells with the PKC inhibitor GF109203X. E(2) caused a specific dose- and time-dependent increase in expression of PKC delta protein of twofold, whereas PKC delta mRNA was unaffected by E(2) over a 12-day culture period. Treatment of cells with 500 ng/ml rPL-1 for the final 4 days of a 12-day culture in the absence of E(2) had no effect on PKC delta protein or mRNA expression, while treatment with 500 or 3000 ng/ml rPL-1 in the presence of E(2) significantly enhanced both PKC delta protein and mRNA expression (up to threefold). These results show that two of the major regulators of luteal function in the second half of pregnancy in the rat, E(2) and rPL-1, cooperate to regulate PKC delta expression in luteinized granulosa cells.     

Origins of cerebral palsy

Analyses were undertaken to determine the causes of cerebral palsy in a prospective study of 43,437 full-term children. Presumed causes were found for about 71% of the 34 quadriplegic and 40% of the 116 nonquadriplegic patients with cerebral palsy. Risk estimates based on predictive models, adjusted for multiple factors, suggest that 53% of the quadriplegic patients with cerebral palsy could be attributed to congenital disorders, 14% to birth asphyxia, and 8% to other identified disorders. Thirty-five percent of the nonquadriplegic patients with cerebral palsy could be attributed to congenital disorders and 6% to other disorders. In the victims of cerebral palsy, characteristic consequences of birth asphyxia were more often the result of nonasphyxial disorders. These included meconium in the amniotic fluid, low 10-minute Apgar scores, neonatal apnea spells, seizures, persisting neurologic abnormalities, and slow head growth after birth.     

Nasal intermittent positive-pressure ventilation offers no advantages over nasal continuous positive airway pressure in apnea of prematurity

A prospective, randomized, cross-over trial was performed to compare the efficacy of nasal intermittent positive-pressure ventilation with nasal continuous positive airway pressure in infants of less than 32 weeks of gestation. Continuous positive airway pressure was delivered at end-expiratory pressures of 4 cm H2O, while peak pressures of 20 cm H2O and end-expiratory pressures of 4 cm H2O were used during nasal intermittent positive-pressure ventilation at ventilatory rates of 20 breaths per minute. The frequency and extent of apnea and bradycardia during a 6-hour period in a patient receiving nasal continuous positive airway pressure were compared with a similar crossover period of nasal intermittent positive-pressure ventilation. Although the infants had slightly less frequent episodes of apnea per hour (0.6 +/- 0.7 vs 0.5 +/- 0.7) and bradycardia per hour (1.2 +/- 1.3 vs 0.9 +/- 1.0) during nasal intermittent positive-pressure ventilation, these differences were not significant. There were no significant differences in the severity of these events as assessed by the duration and fall in transcutaneous oxygen pressure during apnea and heart rate during bradycardia. There were no significant changes in blood gases throughout the study. Nasal intermittent positive-pressure ventilation appears to have no advantages over nasal continuous positive airway pressure in preventing apnea and does not alter gas exchange in infants of less than 32 weeks of gestation.     

Platinum-based combination chemotherapy for malignant mixed mesodermal tumors of the ovary

Although considerable clinical data are available to guide treatment decisions for patients with ovarian epithelial malignancies, therapy for the rare malignant mixed mesodermal (mullerian) tumor (MMMT) of the ovary is poorly studied. Ten untreated patients diagnosed with primary ovarian MMMT were managed with cis-platinum-based combination chemotherapy from 1980 to 1985. Six of the 10 patients were stage III suboptimal with evaluable residual disease; 4 of these 6 had CRs with a median duration of response of 13 months. The remaining 2 patients had PRs, of 2 and 11 months duration. Four patients had stage III optimal disease; 1 progressed at 7 months, 1 progressed at 16 months and the other 2 patients have no clinical evidence of disease at 12+ and 22+ months. Despite impressive initial response rates, survival overall was poor, with a median survival for all 10 patients of 16+ months.