Apparent Smith-Lemli-Opitz syndrome in a child with a previously undescribed form of mucolipidosis not involving the neurons

A diagnosis of Smith-Lemli-Opitz syndrome was made shortly after birth in a small-for-dates infant, on the basis of a characteristic face, penoscrotal hypospadias, bilateral postaxial hexadactyly, and bilateral syndactyly of toes 2-3. The clinical course was marked by failure to thrive, severe delay, refractory myoclonic jerks beginning at age 2 months, and increasing hepatosplenomegaly. He developed corneal clouding and increased gingival hypertrophy and died at age 18 weeks. Autopsy disclosed widespread storage of mucopolysaccharides and lipids within the macrophages and, to a lesser extent, parenchymal cells, of all organ systems. There was extensive demyelination of the cerebral white matter, and dystrophic calcification in the cerebrum, cerebellum, and brainstem. There was no evidence of primary neuronal involvement in the storage. Although the chance concurrence of 2 uncommon diseases is rare, a causal link between the clinical anomalies and the storage disorder cannot be argued convincingly on the basis of one case. Careful pathologic studies of other children who die with clinical signs compatible with Smith-Lemli-Opitz syndrome are indicated.     

Hepatic uptake of small-latticed immune complexes does not alter mononuclear phagocyte system function.

The hepatic and splenic uptake of circulating, small-latticed immune complexes and the effect of these complexes on the hepatic mononuclear phagocyte system (MPS) were examined in mice. The small-latticed immune complexes were prepared at fifty-fold antigen excess. The clearance from circulation and uptake by the liver and spleen of two probes of MPS function, aggregated human IgG and aggregated mouse albumin, were quantified. The hepatic uptake of a dose of small-latticed complexes, containing 5 mg of antibodies, at 1 hr was comparable with the uptake of a similar dose of complexes that contained large-latticed complexes. At later time points, the hepatic uptake of the small complexes was significantly less than that of the larger complexes. The splenic uptake of the small-latticed complexes was less at all time points. Doses of the small-latticed complexes, ranging from 1 to 5 mg antibody in the complexes, produced no significant inhibition of the clearance or organ uptake of the MPS probes when administered 1 hr after the preload injections. In contrast, large-latticed complexes produced a dose-dependent delay in clearance due to a decreased hepatic uptake of the probes. These observations showed that small-latticed immune complexes were ineffectively removed by the hepatic MPS and that the presence of large quantities of small-latticed complexes in circulation did not alter MPS function.     

The role of the endoscopic biopsy in the diagnosis of gastric lymphoma: a morphologic and immunohistochemical reappraisal

Forty-three endoscopic biopsies from 29 patients with confirmed gastric lymphoma (GL) were analyzed retrospectively to establish the morphologic criteria of greatest diagnostic significance. An average of 10 tissue samples was obtained at each endoscopy. In 44% of the cases, lymphoma was discovered in only one or two of the tissue portions. Eighteen lymphomas were primary, six were probably primary, and five were generalized. The diagnosis of lymphoma was originally suspected or established in 46% of the biopsies. However, a review of the histologic sections indicated that the changes, either diagnostic of or compatible with lymphoma, were present in 75% and 18% of the sections, respectively. Most diagnostic errors consisted of confusion with diffuse lymphoid infiltrates in chronic gastritis and/or peptic ulcer, and less frequently with poorly differentiated carcinoma. In those cases confused with chronic gastritis or peptic ulcer, biopsies showed centrocyte-like cells of the standard type or small lymphocytes which produced: (1) a marked increase in density of the lymphoid infiltrate in the gastric mucosa, (2) massive substitution of gastric glands by lymphoid infiltration, and (3) a collection of lymphocytes infiltrating and partially destroying isolated glands (lymphoepithelial lesion). From 48 biopsies having intense benign lymphoid infiltrates, three were interpreted (by means of a blinded study) as compatible with GL. In poorly differentiated neoplasms (blastic and pleomorphic types), cytologic features were sufficient to diagnose GL or malignant neoplasms; immunohistochemical techniques were useful to define their lymphoid nature. It is concluded that many GLs can be suspected or correctly diagnosed by routine endoscopic biopsy.     

Isolation of verotoxin-producing Escherichia coli O-rough:K1:H7 from two patients with traveler's diarrhea.

Two Escherichia coli O-rough:K1:H7 strains producing verotoxin 1 that were isolated from stool samples of two travelers with diarrhea who consulted our clinic after trips to the Indian Subcontinent and Central America were characterized. Both strains were sorbitol negative, the same phenotype presented by E. coli O157:H7, but in contrast they were beta-glucuronidase positive. Low-frequency restriction analysis of chromosomal DNA and pulsed-field gel electrophoresis and repetitive extragenic palindrome-PCR showed that both strains were epidemiologically related. The illness was self-limited in both cases but involved long-duration, watery diarrhea (10 to 50 days) accompanied by abdominal cramps and flatulence. This serotype should be taken into account as a possible cause of traveler's diarrhea.     

Mecanotransduction and Endothelial Cells

1 IntroductionAtherosclerosis preferentially occurs in areas of complex blood flow where there are disturbed flow and low fluid shear stress, whereas laminar blood flow and high shear stress are atheroprotective~([1]). Reports of others and our studies suggest a steady laminar flow decreases some molecules and genes expression of vascular endothelial cells (EC) that may promote atherosclerosis, as well as it can differentially regulate production of many vasoactive factors at the level of gene expression an...     

Effects of the ras-related rap2 protein on cellular proliferation.

Ras oncogenes encode 21-kDa (p21s) GTP binding proteins that are capable of transforming immortalized cells in culture. The ras-related rap1A/Krev-1/smgp21A protein, that exhibits a similar structural organization and contains the same effector domain as ras proteins, antagonizes ras-transformation. In order to investigate whether the closely related (61% identical) rap2 protein had similar capacities, the corresponding cDNA was inserted into constitutive as well as inducible mammalian expression vectors. Neither the wild-type, nor an "activated" mutant carrying a glycine-to-valine substitution at position 12, had any transforming activity. Several independent lines of evidence demonstrate that the rap2 protein exhibits neither growth-promoting nor growth-inhibitory effects, and that its over-expression does not interfere with ras-induced transformation. Thus, in spite of their great similarities, the rap1A/Krev-1/smgp21A and rap2 proteins have distinct physiological properties.     

15-Hydroxyeicosatetraenoic acid inhibits neutrophil migration across cytokine-activated endothelium.

15-hydroxyeicosatetraenoic acid (15-HETE) is an eicosanoid, formed by the actions of 15-lipoxygenase, epoxygenases, and cyclooxygenases on arachidonic acid, whose tissue levels are often elevated during inflammation. The present study demonstrates that 15(S)-HETE is a potent inhibitor of polymorphonuclear neutrophil (PMN) migration across cytokine-activated endothelium in vitro. 15(S)-HETE is rapidly esterified into PMN phospholipids, and we report that 15-(S)-HETE-remodeled PMN displayed blunted adhesion to, and migration across, human endothelial cells that had been activated with either interleukin-1 beta or tumor necrosis factor-alpha Several lines of evidence suggested that 15(S)-HETE inhibited PMN transmigration by attenuating PMN responsiveness to endothelial cell-derived platelet-activating factor (PAF). The inhibitory action of 15(S)-HETE on transmigration was not restricted by the profile of adhesion molecules expressed by cytokine-activated endothelium. Interleukin-1 beta and tumor necrosis factor-alpha induce PAF production by endothelium, and PMN migration across cytokine-activated endothelium was inhibited by a PAF receptor antagonist. PMN migration across endothelium in response to exogenous PAF was dramatically inhibited following exposure of PMN to 15(S)-HETE. Furthermore, 15(S)-HETE-remodeled PMN displayed impaired cytoskeletal and adhesion responses when stimulated by exogenous PAF, two pivotal events in PMN migration across activated endothelium. 15(S)-HETE seemed to attenuate PMN responsiveness to PAF by inhibiting membrane-associated signal transduction events. In keeping with this interpretation, remodeling of PMN phospholipids with 15(S)-HETE was associated with a sixfold reduction in the affinity of specific high-affinity PAF receptors for their ligand and impaired PAF-triggered IP3 generation. In contrast, PMN adhesion responses stimulated by calcium ionophore or activators of protein kinase C remained intact. These results provide further evidence that 15(S)-HETE may be an important endogenous inhibitor of PMN-endothelial cell interaction that serves to limit or reverse neutrophil-mediated inflammation in vivo.