Beta-adrenergic hyperresponsiveness in compensated hypothyroidism associated with Down syndrome

Although compensated hypothyroidism (CH) is the most common thyroid impairment in Down syndrome (DS), its pathogenesis remains elusive. Because primary gonadal failure is another DS-associated endocrinopathy, we hypothesized that an impaired signal-transduction pathway shared by several organs may provide a unifying explanation for both endocrinopathies. We assessed two possible transduction-pathway components associated with CH in DS: the G-protein adenylate-cyclase (AC) system and beta-adrenergic responsiveness, previously reported to be enhanced in DS fibroblasts. Twenty-one DS patients and 14 control subjects were studied. Peripheral mononuclear cells (PMCs) were incubated with G-protein modulators [prostaglandin E1 (PGE1) and cholera toxin (CTx)], an AC stimulator (forskolin), and a beta-adrenergic agonist (isoproterenol), and cAMP levels were determined. All participants had normal plasma thyroid hormone levels, but 11 of the DS patients had elevated TSH levels (hTSH), whereas in the 10 others, they were normal (nTSH). cAMP levels in response to forskolin, PGE1, and CTx were similar in all groups, whereas isoproterenol-stimulated cAMP levels were significantly higher in the hTSH group than in the nTSH group and control subjects (45 +/- 30 versus 22 +/- 9 and 21 +/- 9 pmol . 10(6) cells(-1) . 10 min(-1), respectively; p = 0.02). Four patients in the DS hTSH subgroup had impaired sexual development. We found hyperresponsiveness of PMCs to a beta-adrenergic agonist in a subgroup of DS patients with CH. If this observation is applicable to the thyroid gland, then it may reflect a mechanism in which negative effects on cell growth or responsiveness to TSH lead to CH.     

Splenic hamartoma with bizarre stromal cells

Splenic hamartoma is a rare entity characterized by disorganized red pulp tissue in the absence of interspersed white pulp. We report 3 cases with scattered bizarre stromal cells, a feature not previously reported in the literature. The patients were adults who presented with abdominal pain (2 cases) or were incidentally found to have a splenic mass (1 case). The lesion was solitary, circumscribed, and unencapsulated, comprising disorganized slit-like, tubular, ectatic or cavernous vascular channels. There was a loose stroma that contained lymphocytes, plasma cells, siderophages, and fibrin exudate. Scattered haphazardly were isolated bizarre large cells with oval, convoluted, or multilobated nuclei; pale or smudged chromatin; and scanty cytoplasm. Mitotic figures were not found. The bizarre cells were negative for lymphoid, dendritic cell, histiocytic, myeloid, endothelial, epithelial, and melanocytic markers. Only rare bizarre cells stained for desmin in 1 case. It is important to recognize this morphologic variant of splenic hamartoma in order not to misinterpret the bizarre cells as being indicative of a malignancy.     

Adrenocortical oncocytic tumors: report of 10 cases and review of the literature

Ten additional adrenocortical oncocytic tumors are presented: 2 benign oncocytomas, 4 borderline oncocytomas of uncertain malignant potential, and 4 oncocytic carcinomas. Histologically all tumors were entirely or predominantly composed of oncocytes. Immunohistochemically all tumors were immunoreactive for mitochondrial antigen mES-13. Electron microscopy was performed in 8 cases and was confirmatory of the oncocytic cell change. The morphologic parameters of the Weiss system, considered to be predictive of the biologic behavior of conventional (nononcocytic) adrenocortical tumors, are reviewed in the context of their possible application to the oncocytic tumor variant. Proposed major criteria (high mitotic rate, atypical mitoses, venous invasion) and minor criteria (large size and huge weight, necrosis, capsular invasion, sinusoidal invasion) in distinguishing malignant tumors are discussed, and definitional criteria (predominantly cells with eosinophilic and granular cytoplasm, high nuclear grade, diffuse architectural pattern) in common with all types of oncocytic tumors are outlined. The authors' proposed working rules for diagnostic categorization of oncocytic adrenocortical tumors are defined, with the presence of 1 major criterion indicating malignancy, 1 to 4 minor criteria indicating uncertain malignant potential (borderline), and the absence of all major and minor criteria indicative of benignancy. Using these criteria, the diagnosis of malignancy was straightforward in 3 of the 4 cases designated as oncocytic carcinoma (presence of at least 2 major criteria and all the minor criteria), while in 1 case the original diagnosis of benign oncocytoma was reversed to malignant following critical review of the original pathologic material after local tumor recurrence. Tumor recurrence occurred in 2 carcinomas at 8 and 20 months, respectively, and was followed in 1 case by the patient's death. The third patient expired at 6 months from unrelated causes, and the fourth patient is free of disease at the relatively short follow-up interval of 6 months. Regarding the 4 patients with borderline tumors, all are alive with no evidence of disease, with follow-up ranging from 10 to 61 months (mean 38.7 months). The 2 benign tumors have a follow-up of 25 and 30 months, respectively. Diagnostic difficulties are delineated and a complete review of the literature on this topic has also been performed.     

Acropustulosis infantilis in an 8-year-old girl

We report on an 8-year-old female patient showing the typical lesions of acropustulosis of infancy. Our case is unusual because infantile acropustulosis mostly affects male patients and occurs during the first year of life, persisting for a period of approximately 2 years.     

Kidney Changes in Mice due to Oriental Hornet (Vespa orientalis) Venom: Histological and Electron Microscopical Study

Abstract: Administration to mice of Vespa orientalis venom was found to cause acute tubular necrosis of the kidney. The proximal tubular epithelial cells showed an abundance of autophagic vacuoles, suggesting disintegration of mitochondria. A few necrotic cells were found. The mechanism of the action of the venom on the kidney tubule cells is as yet unknown but there is evidence for direct effect of the venom on the mitochondria.     

Rapid purification of extracellular and intracellular Moloney murine leukemia virus

Summary The present study demonstrates the advantages of a combination of concentration by polyethylene glycol-6000 and Sepharose Cl-4B chromatography as a rapid procedure for retroviruses purification. This procedure can be completed within 3 hours, providing a high degree of virus purification with minimal damage to its structural and biological properties. Using transmission electron microscopy we observed many intracellular type-C virions in cytoplasmic vacuoles of 3T3/NIH cells chronically infected with Moloney murine leukemia virus. There intracellular virions could be isolated from postmitochondrial cytoplasmic fractions prepared from the infected cells by a procedure which minimized its contamination by extracellular free or membrane-bound virions. SDS-polyacrylamide gel electrophoresis showed that the intracellular and extracellular virions contained similar protein composition.With 5 Figures     

Involvement of dorsal root ganglia in Fabry''s disease.

Bouts of shooting pain along the extremities are common in the early stages of Fabry's disease. No pathological explanation has been advanced to clarify the mechanism of such pain. In the present case neuronal storage of glycolipid was confined to dorsal root ganglia neurones only. It is suggested that this may explain the shooting pain in Fabry's disease. In hereditary sensory radicular neuropathy, familial dysautonomia, and tabes dorsalis, changes in dorsal root ganglia cells cause similar clinical signs and thus it may be concluded that shooting pains in Fabry's disease may be caused by damage to dorsal root ganglia neurones.     

A pustular form of loxoscelism (bite of the brown recluse spider)

We report on a 42-year-old man who showed the typical clinical picture after being bitten by a brown recluse spider (Loxosceles reclusa). The patient developed a pustular eruption during the acute phase of the disease. To the best of our knowledge, this is the first report on pustular loxoscelism.