Evidence for a NO synthase in porcine platelets which is stimulated during activation/aggregation

Abstract: We tried to characterize the porcine platelet nitric oxide (NO) synthase and its L-arginine (L-arg)/NO metabolism. Using RT-PCR we could show a constitutive endothelial NOS (ecNOS) and an inducible NOS (iNOS) similar mRNA in platelets. The NOS protein could be evidenced by an ecNOS specific antibody which also bound in platelets. This finding could be confirmed by Western blot showing an ecNOS in the membrane but not the cytosolic fraction; iNOS protein could not be detected. Using NADPH-diaphorase staining we could show NO synthase in preactivated platelets but not in resting platelets, indicating that the platelet NOS may be activated during platelet activation/aggregation. Porcine L-arg plasma levels (9.31 × 10^–5 mol/l ± 10%) could be shown to be in the same range as human plasma levels. Moreover, we could show that the NO precursor L-arg and hydroxy-L-arginine (OHarg) concentration dependently inhibited collagen induced platelet aggregation. Summarizing these results confirm the existence of and further characterize porcine platelet NO synthases.     

Imaging findings of the developing temporal bone in fetal specimens.

PURPOSETo trace the development of the normal fetal temporal bone by means of plain radiography, MR, and CT.METHODSEighteen formalin-fixed fetal specimens, 13.5 to 24.4 weeks'' gestational age, were examined with a mammographic plain film technique, CT, and MR imaging at 1.5 T. Temporal bone development and ossification were assessed.RESULTSThe membranous labyrinth grows with amazing rapidity and attains adult size by the middle of the gestation period. The cochlea, vestibule, and semicircular canals are very prominent and easily recognized on MR images. The otic capsule develops from a cartilage model. Ossification of the otic capsule proceeds rapidly between 18 and 24 weeks from multiple ossification centers that replace the cartilaginous framework. The mastoid, internal auditory canal, vestibular aqueduct, and external auditory canal continue to grow after birth.CONCLUSIONThe study of fetal developmental anatomy may lead to a better understanding of congenital disorders of the ear. Faster MR scanning techniques may provide a method for in utero evaluation of the fetal temporal bone.     

Fas receptor expression on B-lineage cells

Mice homozygous for the lpr mutation have B and T cell defects and develop autoantibodies, suggesting that lpr plays a role in their genesis. The lpr defect has been identified as a mutation in the apoptosis-associated Fas receptor (FasR) gene. To begin to define the role of FasR in B cells, we have surveyed FasR expression on B-lineage cells from early progenitors in the bone marrow through their maturation in the periphery. Contrary to some reports, we found that FasR is expressed on B cells at all stages of their development and is highest on germinal center B cells. FasR is not expressed on lpr/lpr-derived cells. These data are consistent with the idea that lpr/lpr mice have an intrinsic B cell defect that may be manifested in developing as well as peripheral B cells. An unexpected finding is that B-1 (CD5) B cells do not constitutively express FasR: FasR becomes detectable on B-1 B cells only after activation.     

Attitudes and behaviors of African-American and Mexican-American women delivering newborns in inner-city Los Angeles.

To study some of the factors relating to the care of mothers and newborns in an inner-city hospital, three sources of information were reviewed: an obstetric database including information on prenatal care and perinatal mortality, a database of all admissions to the hospital neonatal intensive care unit over the past 5 years, and a detailed questionnaire concerning attitudes and behaviors of recently delivered women. While analyses from these hospital-based data are not conclusive, the results add evidence for the following propositions: 1) Optimal prenatal care is infrequently obtained by mothers delivering at inner-city hospitals. Lack of prenatal care is clearly associated with increased perinatal mortality. While the need for prenatal care is appreciated by 98% of the mothers in this sample, the most frequent reasons why prenatal care is not obtained earlier or more frequently involve knowledge about and access to prenatal care. 2) Inner-city mothers, in general, manifest attitudes and behaviors that promote the welfare of their pregnancies and newborns. These attitudes and behaviors are in stark contrast to those that are frequently attributed to inner-city women by the media. 3) Acute perinatal medical and nursing care are perceived by many postpartum women as suboptimal, particularly in terms of the lack of respect shown to patients by nurses and doctors. 4) Improved acute obstetric and neonatal care improves perinatal morbidity and mortality of infants delivered at inner-city hospitals.     

Study of the role of vitamin B12 and folinic acid supplementation in preventing hematologic toxicity of zidovudine

Abstract: A prospective, randomized study was conducted to evaluate the role of vitamin B₁₂ and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4 + cell counts < 500/mm³ were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B₁₂ (1000 μg monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B₁₂ and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm³ and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B₁₂ or folate levels and development of myelosuppression. Vitamin B₁₂ and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.     

Early onset Alzheimer's disease in a South American pedigree from Argentina

We report the clinical, SPET, immunohistochemical and DNA features of an early-onset familial Alzheimer's disease (FAD) in an Argentine pedigree of South American indian ethnic background. Pedigree spans 5 generations comprising more than 110 biological relatives. Clinical data supported the diagnosis of early onset FAD (mean age at onset 38.9 years) in 10 family members, including 3 with pathological confirmation (mean age at death 48.5). The pattern of transmission suggested autosomal dominant inheritance. Prominent features were mood changes, early language impairment, myoclonus, seizures and cerebellar signs. SPET displayed bilateral frontal, temporo-parietal and cerebellar hypoperfusion in early stages and in an asymptomatic member at risk, suggesting that SPET may have predictive value in this family. Immunohistochemistry showed β amyloid deposits within neuritic plaques and vessel walls and no anti-PrP immunoreactivity. DNA analysis showed no abnormalities in the β amyloid precursor protein gene. The identification of additional genetic defects in well characterized independent FAD pedigrees will contribute to the understanding of the pathogenesis of Alzheimer's disease.     

The Prospective Assessment of Autonomic Nerve Function by Pupillometry in Adolescents with Type 1 Diabetes Mellitus

The study aimed to compare the longitudinal assessment of autonomic nerve function by computerized infrared pupillometry and standard cardiovascular tests in adolescents with diabetes. Adolescents (n = 150) were assessed at two time points (T1 and T2). The median time interval between assessments was 1.5 (range 0.9–3) years. At T1 the median age was 14.5 (range 8.3–19.5) years and the median duration was 6.5 (range 1.1–16) years. The pupillary variables assessed included the resting pupil diameter, the maximum constriction velocity, and the reflex amplitude of constriction. Heart rate reflexes were assessed in response to deep breathing, the Valsalva manoeuvre, and on standing from a lying position (30/15 ratio). Between visits there was a significant decrease in maximum constriction velocity (6.0 mm s^?1 vs 6.3 mm s^?1, p = 0.0001) and resting pupil diameter (6.2 mm vs 6.3 mm, p = 0.001). At reassessment pupillary abnormalities increased from 32 (21 %) to 45 (30%), with 17 (54 %) of the initial abnormalities persisting. Adolescents with abnormally slow maximum constriction velocity compared to those with normal maximum constriction velocity had a higher glycated haemoglobin (HbA_1c%) at T2 (p = 0.02) and between assessments (p = 0.01). Cardiovascular test abnormalities did not increase between visits and the persistence of initial abnormalities was low (21 %). In summary, pupillometry appears a more sensitive test of autonomic nerve dysfunction in adolescents with diabetes than assessment of cardiovascular reflexes.     

SQUAMOUS CELL CARCINOMA IN KAUAI, HAWAII

Background. It is estimated that over 100,000 new cases of squamous cell carcinoma are diagnosed in the United States annually. This number is compounded by an increasing concern over the ozone layer depletion and the continued sunbathing behavior of many individuals. This could be particularly acute in Hawaii, which may have the highest rates of skin cancer in the country. We believe the updated information on skin cancer is essential to address the magnitude of the problem. Methods. A prospective 5-year population-based incidence study was conducted on Kauai, Hawaii, between 1983 and 1987 to investigate the frequency of squamous cell carcinomas in resident Caucasians. Results. A total of 58 residents, 37 men and 21 women, were identified with an initial episode of squamous cell carcinoma during the 5-year period. The average annual incidence rate per 100,000 Kauai Caucasian residents, standardized to the 1980 U.S. white population, was 153 for men and 92 for women with a combined rate of 118. The average patient age was 66.4 years. The head and neck was the most common anatomic site, with the extremities second. Subsequent new squamous cell carcinoma occurred in 13.8% of patients. Only one patient (2%) developed a recurrence after treatment. Twenty-five patients (43%) had basal cell carcinoma simultaneously or at other earlier times. Conclusions. In Kauai the incidence rate of squamous cell carcinoma is the highest yet documented in the United States. No consistent trend in incidence rates was appreciated during this 5-year period.     

Late-onset focal dermal elastosis: clinical and histological features

We describe two patients with lesions clinically resembling pseudoxanthoma elasticum and histologically exhibiting focal elastosis. with normal-appearing elastic fibres in the mid- and deep dermis. We consider that these skin lesions represent a previously undescribed entity, whose pathogenesis appears to be related to the ageing process.