Cowden syndrome and Lhermitte-Duclos disease in a family: a single genetic syndrome with pleiotropy?

Cowden syndrome is an autosomal dominant condition of multiple hamartomas. Patients with this phakomatosis have an increased risk of breast cancer and thyroid tumours. Lhermitte-Duclos disease is usually a sporadic condition of cerebellar ganglion cell hypertrophy, ataxia, mental retardation, and self-limited seizure disorder. We describe a three generation family with Cowden syndrome and Lhermitte-Duclos disease. Karyotyping performed on the peripheral lymphocytes of the proband and her affected mother showed a 46,XX complement. Single strand conformational polymorphism analysis failed to show any germline p53 mutations as a cause of the syndrome in this family.     

Alzheimer''s disease. Beta-amyloid precursor protein expression in the nucleus basalis of Meynert.

The nucleus basalis of Meynert (nbM) was examined using immunocytochemistry for beta-amyloid precursor protein (beta APP) expression in Alzheimer's disease (AD). In mild AD cases, light labeling of the cell body and proximal processes was observed, and small intracellular structures were labeled rarely. In the more severe cases, intense cytoplasmic beta APP labeling was seen, often along with small beta APP-positive structures. Double-labeling experiments demonstrated that in the more severe cases these small structures were also decorated by a neurofibrillary tangle (NFT) antiserum. Other neurons in the severe cases showed incorporation of beta APP into large inclusions, which were also labeled with the NFT antiserum. However, some large inclusions in the severe cases were labeled by the NFT antiserum but contained no beta APP. Extraneuronal NFTs did not show beta APP labeling and did not react with an antibody to the beta-amyloid peptide. These results suggest that increased expression of beta APP coincides with intracellular NFT formation in the nbM, but that the formation of extraneuronal NFTs results in a loss of beta APP immunoreactivity.     

Bacteremia and fungemia in patients with acquired immune deficiency syndrome

Patients with acquired immune deficiency syndrome (AIDS) are known to have identifiable host defense deficiencies, especially deficiencies in cell-mediated immunity. They are at increased risk for developing infections of the bloodstream caused by Cryptococcus neoformans and Salmonella species. However, bacteremias caused by other enteric gram-negative rods and Pseudomonas aeruginosa are found less frequently in patients with AIDS than in patients without AIDS (P less than 0.001 and P less than 0.01, respectively). The findings of specific organisms in blood is consistent with the known types of host defense deficiencies in these patients.     

Clinical genetic counselling for familial cancers requires reliable data on familial cancer risks and general action plans

Familial cancer clustering, without obvious heritability, poses a major challenge for current cancer risk assessment and management. Reliable determination of familial risks for cancer is important for clinical genetic counselling, but medically verified data on familial risks for many malignancies have been limited. However, the nationwide Swedish Family-Cancer Database allows a reliable characterisation of familial risk for all major neoplasms. Even though alert genetic counsellors and certainly clinical cancer geneticists will consider familial cancer clustering in their purview, the standard medical referral systems, which have already been shown to be poor in capturing and referring families at high risk for heritable cancers, are unlikely to ascertain familial aggregations of other cancers that are not known to belong to an inherited cancer syndrome. The data will be helpful in implementing evidence based guidelines for helping the general medical system to ascertain and refer even familial cancer clusters to cancer genetics professionals.     

Seroprevalence of human herpesvirus-8 in blood donors from different geographical regions of Argentina, Brazil, and Chile

Human herpesvirus-8 (HHV-8) causes Kaposi's sarcoma (KS) and lymphoproliferative disorders in both HIV-infected and uninfected patients. HHV-8 has a worldwide occurrence but infection rates vary according to a combination of geographic and behavioral risks. The main transmission route seems to be sexual, nevertheless, nasal secretions, saliva, blood, and organ graft have been proposed. HHV-8 was postulated as a new infectious agent for screening in blood donors. The aim of this study was to evaluate the prevalence of antibodies against HHV-8 antigens in blood donors of South America. Serum samples from 2,470 blood donors from Argentina, Brazil, and Chile corresponding to five geographic regions were studied by indirect immunofluorescence assay (IFA). Seroprevalence rate was 3.7% (92/2,470; 95% CI 2.9-4.5) in the entire blood donor population distributed as follows: Argentina, 4.0% (Buenos Aires city, 4.3%; Bahia Blanca, 2.4%; and Córdoba, 4.0%), Campinas (Brazil), 2.8%; and Santiago de Chile, 3.0%. There was no difference (P>0.05) between men and women or age related, except in Brazil where positive cases were 30-49-year-old males. The present study, which includes different geographical areas of multiple countries from South America, has not been done before. The results show similar prevalence rates among the studied zones corresponding to low-prevalence regions. South America is a large sub-continent with a wide spectrum of population and geographical characteristics, thus, more HHV-8 prevalence studies should be necessary to establish possible regional differences.     

Evaluation of dot enzyme-linked immunosorbent assay for mucocutaneous leishmaniasis and comparison with microplate enzyme immunoassay.

A dot enzyme-linked immunosorbent assay (dot ELISA) was evaluated and compared with a standard microplate ELISA (immunoglobulin G [IgG] ELISA) for the serological diagnosis of mucocutaneous leishmaniasis. The two assays were used to test 113 serum specimens from the following groups: normal individuals and patients with deep mycoses, toxoplasmosis, mucocutaneous leishmaniasis, visceral leishmaniasis, Chagas' disease, malaria, and schistosomiasis. Both tests exhibited cross-reactivity when testing specimens from cases of visceral leishmaniasis and Chagas' disease. The dot ELISA proved to be economical with respect to use of reagents and was easy to perform. Interpretation could easily be made by visual inspection of reaction endpoints in the nitrocellulose disks, obviating the need for spectrophotometric readings. There were no significant differences in sensitivity between the dot ELISA and the IgG ELISA at a cutoff level either of 20 or 40. However, its most remarkable feature was the high specificity compared with that of the IgG ELISA. Because of its ease of performance and high sensitivity and specificity, the dot ELISA should be an excellent test to be executed in the field during seroepidemiological surveys.     

Intracellular mechanisms governing the acute phase of β-endorphin secretion from the corticotrope in vitro

It is not certain which protein kinase (A, C or both) is involved in the acute phase of β-endorphin (β-EP) release stimulated in the corticotrope by vasopressin (VP) and corticotropin-releasing factor (CRF). We have employed an isolated ovine anterior pituitary cell superfusion system to determine the dynamic effects of forskolin, a protein kinase A (PKA) stimulator, and phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator. Both secretagogues stimulated β-EP release within 5 min and therefore both PKA and PKC are potential mediators of the acute phase of hormonal stimulation of the corticotrope. Pretreatment with PMA specifically desensitized the pituitary cell columns to subsequent PMA exposure while not significantly altering sensitivity to forskolin or 50 mM KCl.     

Hb FM-Fort Ripley: Confirmation of autosormal dominant inheritance and diagnosis by PCR and direct nucleotide sequencing

We describe a normal neonate who presented at four days of age with asymptomatic cyanosis. There was no evidence of cardiac or pulmonary abnormality and an extended family history included 13 other affected family members with asymptomatic cyanosis lasting one to three months. Polymerase chain reaction (PCR) amplification and direct nucleotide sequencing of the proband's Gγ chain gene revealed the mutation at codon 92 (CAC→TAC) previously shown in haemoglobin FM-Fort Ripley (α₂γ₂^{Gγ 92 (F8) His→Tyr}). This is the first family with Hb FM-Fort Ripley reported so far. It demonstrates autosomal dominant inheritance of this condition and incomplete penetrance. © 1994 Wiley-Liss, Inc.     

Carrier Frequency of the Bloom SyndromeblmMutation in the Ashkenazi Jewish Population

Bloom syndrome is more common in individuals of Ashkenazi Jewish descent than in any other population, and one particular mutation in the Bloom syndrome gene,blm^Ash,is homozygous in nearly all Ashkenazi Jewish persons with Bloom syndrome. We have determined the frequency ofblm^Ashin 1491 Ashkenazi Jewish persons with no known history of Bloom syndrome and found that 1 in 107 persons was heterozygous. Although not common, genetic screening for Bloom syndrome is feasible in this population.