Characterization of Leishmania colombiensis sp. n (Kinetoplastida: Trypanosomatidae), a new parasite infecting humans, animals, and phlebotomine sand flies in Colombia and Panama.

Characterization of Leishmania colombiensis sp.n. is presented, which on the basis of biological and molecular criteria, appears to be a new member of the L. braziliensis complex. A total of nine isolates of the new parasite were made in Colombia and Panama between 1980 and 1986: two from human cases of cutaneous leishmaniasis, six from phlebotomine sand flies, and one from a sloth. Although most closely related to L. lainsoni, L. colombiensis sp.n. is clearly distinguishable from other members of the genus by its reactivity with monoclonal antibodies, isoenzyme electrophoresis, and restriction endonuclease fragment patterns of kinetoplast DNA (k-DNA).     

Agalactosyl IgG: an aid to differential diagnosis in early synovitis

Sixty consecutive patients presenting with early-onset synovitis were studied by measuring rheumatoid factor (RF) titers and the percentage of oligosaccharide chains attached to the C gamma 2 domain of IgG that lack galactose (GAL[0]). After 2 years of followup, 39 patients (65%) had developed rheumatoid arthritis (RA), and 21 had developed a variety of other inflammatory joint diseases. A combination of RF positivity and GAL(0) levels above the age-corrected mean gave a positive predictive value for a diagnosis of RA in 94% of these patients. These observations may well have clinical utility.     

Patient-specific transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is one of the leading causes of transfusion-associated mortality. The inadvertent transfusion of neutrophil antibodies can cause pulmonary transfusion reactions and TRALI. However, not all patients transfused with neutrophil antibodies experience transfusion reactions. A 22-year-old man with severe aplastic anaemia (SAA) experienced TRALI after a platelet transfusion. The donor was found to be alloimmunized to human neutrophil antigen (HNA)-3a, an antigen expressed by neutrophils from approximately 90% of Caucasians. Eleven other platelet components from this donor were transfused prior to this event and two caused reactions: one chills and one TRALI. Both episodes of TRALI occurred in the same male patient with SAA. The fact that one patient experienced TRALI following both exposures to anti-HNA-3a from the same donor whereas nine other recipients did not adds evidence to the observation that patient factors make a significant contribution to neutrophil antibody-mediated transfusion reactions.     

Effect of Vagotomy on Serum Gastrin in Patients with Duodenal Ulceration

The concept of increased vagal activity in patients with duodenal ulceration was investigated by observing the effect of medical and surgical vagotomy on the secretion of gastrin. Using a radioimmunoassay technique fasting serum levels of gastrin were determined in 41 normal subjects, 40 patients with duodenal ulceration and 16 patients following vagotomy. The effect of atropine on gastrin secretion was observed in a further 2 patients with duodenal ulceration. The patients with duodenal ulceration were found to have elevated serum levels of gastrin. The 8 patients with “complete” vagotomy had significantly lower serum levels of gastrin than the patients with duodenal ulceration, the patients with an “incomplete” vagotomy or the normal subjects. Post-vagotomy hypergastrinaemia was associated with a recurrence of ulceration. The abolition, by medical or surgical vagotomy, of the hypergastrinaemia associated with duodenal ulceration is consistent with the hypothesis of an increased vagal tone in this disease. These studies also suggest that gastrin estimations may be useful in predicting the presence of inadequate vagotomies.     

Direct sequence analysis of the t(14;18) chromosomal translocation in Hodgkin's disease.

There have been conflicting reports about the occurrence of the t(14;18) chromosomal translocation in Hodgkin's disease. A polymerase chain reaction analysis of biopsy specimens from 21 patients with Hodgkin's disease (HD) has shown the presence of the t(14;18) translocation in four cases (20%). All four patients had nodular sclerosing HD. Direct sequencing of the amplified 14q+ junctions established that the BCL-2 (major breakpoint region) sequence was fused to an Ig joining region (JH) (J6 in all four cases). Different breakpoints were observed in each case but were similar in nature to the breakpoints described in follicular lymphoma. The exact nature and cell of origin in HD remains obscure, although the presence of the t(14;18) translocation may reflect either a B-cell origin in these cases or associated lymphoid hyperplasia.     

Native valve endocarditis caused by dysgonic fermenter type 2 bacilli

A chronic alcoholic who had casual contact with dogs developed subacute tricuspid endocarditis caused by the unusual gram-negative bacillus dysgonic fermenter type 2 (DF-2). Despite recurrent pulmonary emboli, the patient had an apparent successful response to 6 weeks of penicillin therapy. Two weeks after discharge, he experienced congestive heart failure necessitating tricuspid valvulectomy. No evidence of active infection was found in tissue removed at surgery. Despite the achievement of a bacteriologic cure, surgery for residual valve damage is not uncommon in endocarditis, regardless of the microbial etiology. In this case, alcoholism was the only risk factor predisposing to infection presumably contracted from exposure to dogs.     

Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity.

Knockout (KO) mice lacking steroidogenic factor 1 (SF-1) exhibit a phenotype that includes adrenal and gonadal agenesis, impaired gonadotropin expression, and abnormalities of the ventromedial hypothalamic nucleus (VMH). Studies in rodents with lesions of the ventromedial hypothalamus have implicated the VMH in body weight regulation, suggesting that SF-1 KO mice may provide a genetic model of obesity. To prevent death, SF-1 KO mice were rescued with corticosteroid injections, followed by syngeneic adrenal transplants from wild-type (WT) littermates. Corticosterone and ACTH levels in WT and SF-1 KO mice were indistinguishable, documenting restoration of hypothalamic-pituitary-adrenal function. Although weights at earlier ages did not differ significantly from WT littermates, SF-1 KO mice were significantly heavier by 8 wk of age and eventually weighed almost twice as much as WT controls. Obesity in SF-1 KO mice predominantly resulted from decreased activity rather than increased food intake. Leptin was increased markedly, insulin was modestly elevated, and glucose was indistinguishable from WT mice. Although sex steroids in rodents affect weight, ovariectomy did not abolish the weight difference between WT and SF-1 KO mice. These SF-1 KO mice are a genetic model of late-onset obesity that may help elucidate the role of the VMH in weight regulation.     

Identification of tumor suppressor loci on the long arm of chromosome 5 in pulmonary large cell neuroendocrine carcinoma

BACKGROUND: A recent cytogenetic analysis of non-small cell lung cancer revealed hot-spot regions for deletion on the long arm of chromosome 5 and suggested the existence of putative tumor suppressor genes in that region. However, similar studies on genetic alterations in large cell neuroendocrine carcinoma (LCNEC) have been very limited. To our knowledge, this is the first report to screen for the loss of heterozygosity (LOH) and to examine the location of putative tumor suppressor genes on chromosome 5q in LCNEC. OBJECTIVES: To identify tumor suppressor loci on chromosome 5q in LCNEC by microsatellite analysis. PATIENTS AND METHODS: Microsatellite instability and LOH in tumor and normal tissue samples from 13 patients with LCNEC, who had undergone surgical resections, were analyzed by polymerase chain reaction using a panel of 19 microsatellite DNA markers spanning chromosome 5q. RESULTS: LOH was found in all of the 13 tumors (100%) in at least one informative marker tested. The following four common minimally deleted regions were noticed on chromosome 5q: 5q14.3-q21.1; 5q22.2-q23.1; 5q23.3-q33.2; and 5q35.1-q35.2. Three of 13 individual tumors (23.1%) exhibited shifted bands for at least one of the tested microsatellite markers. Shifted bands occurred in 6 of 224 loci (2.7%) tested. CONCLUSION: These data suggest the presence of at least four tumor suppressor loci on chromosome 5q in LCNEC, and further investigations into cloning candidate tumor suppressor genes are warranted.