Summary. More precise analysis of causes of death is needed to focus research efforts and improve morbidity and mortality in sickle cell disease. In this study, the morphological evidence of the cause of death was studied in 306 autopsies of sickle cell disease, which were accrued between 1929 and 1996. The most common cause of death for all sickle variants and for all age groups was infection (33-48%). The terminal infection was heralded by upper respiratory tract syndromes in 72AE6% and by gastroenteritis in 13AE7%. The most frequent portal of entry in children was the respiratory tract but, in adults, a site of severe chronic organ injury. Other causes of death included stroke 9AE8%, therapy complications 7AE0%, splenic sequestration 6AE6%, pulmonary emboli/thrombi 4AE9%, renal failure 4AE1%, pulmonary hypertension 2AE9%, hepatic failure 0AE8%, massive haemolysis/red cell aplasia 0AE4% and left ventricular failure 0AE4%. Death was frequently sudden and unexpected (40AE8%) or occurred within 24 h after presentation (28AE4%), and was usually associated with acute events (63AE3%). This study shows that the first 24 h after presentation for medical care is an especially perilous time for patients with sickle cell disease and an acute event. Close monitoring and prompt aggressive treatment are warranted.

Serum response factor (SRF) is a MADS box transcription factor that has been shown to be important in the regulation of a variety of muscle-specific genes. We have previously shown SRF to be a major component of multiple cis/trans interactions found along the smooth muscle gamma-actin (SMGA) promoter. In the studies reported here, we have further characterized the role of SRF in the regulation of the SMGA gene in the developing gizzard. EMSA analyses, using nuclear extracts derived from gizzards at various stages in development, showed that the SRF-containing complexes were not present early in gizzard smooth muscle development, but appeared as development progressed. We observed an increase in SRF protein and mRNA levels during gizzard development by Western and Northern blot analyses, with a large increase just preceding an increase in SMGA expression. Thus, changes in SRF DNA-binding activity were paralleled with increased SRF gene expression. Immunohistochemical analyses demonstrated a correspondence of SRF and SMGA expression in differentiating visceral smooth muscle cells (SMCs) during gizzard tissue development. This correspondence of SRF and SMGA expression was also observed in cultured smooth muscle mesenchyme induced to express differentiated gene products in vitro. In gene transfer experiments with SMGA promoter-luciferase reporter gene constructs we observed four- to fivefold stronger SMGA promoter activity in differentiated SMCs relative to replicating visceral smooth muscle cells. Further, we demonstrate the ability of a dominant negative SRF mutant protein to specifically inhibit transcription of the SMGA promoter in visceral smooth muscle, directly linking SRF with the control of SMGA gene expression. Taken together, these data suggest that SRF plays a prominent role in the developmental regulation of the SMGA gene.

Atrophic and proliferative changes in the prostate gland are regarded as beginning in middle age and characterizing the prostates of older men. A total of 51 prostates of men between 19 and 29 years old demonstrated a spectrum of proliferative abnormalities, including ductal and glandular hyperplasia, atypical hyperplasia, dysplasia, carcinoma in situ and incipient adenocarcinoma. The majority of the prostates also contained substantial areas of atrophy. Patterns of atrophic change included cystic dilatation of glands with flattened epithelium apparently secondary to obstructive hyperplasia of ductal epithelium, areas comparable to sclerotic atrophy of the aged prostate and segments having the appearance of a prepubertal unstimulated prostate. These observations contrast sharply with conventional concepts of the biology of the prostate gland, and suggest a number of hypotheses regarding the early antecedents and evolution of prostatic carcinoma and cancer in general.

A trichomonad flagellate, Tritrichomonas mobilensis n. sp., is described from the large intestine of the squirrel monkey, Saimiri boliviensis boliviensis. The organism has a lanceolate body 7-10.5 micrometers in length; a well developed undulating membrane; a stout, tubular axostyle with periaxostylar rings that terminate in a cone-shaped segment projecting from the posterior end of the cell; and a moderately wide costa. The anterior flagella are about as long as the body, and the recurrent flagellum is of the acroneme type. All its characteristics suggest that the new species belongs in the Tritrichomonas augusta type of the subfamily Tritrichomonadinae.

Spermatozoa have not previously been described within the prostate gland. Nine of one hundred prostates of nonhospitalized males obtained from autopsy during the course of medicolegal death investigation were found to contain spermatozoa. The potential role of spermatozoa in the pathogenesis of corpora amylacea/calculi formation, granulomatous inflammation, local antigenic stimulation, and carcinogenesis is considered.