Association of MSX1 and TGFB3 with nonsyndromic clefting in humans

Nonsyndromic cleft lip with or without cleft palate (CL/P) and nonsyndromic cleft palate only (CPO) are common congenital anomalies with significant medical, psychological, social, and economic ramifications. Both CL/P and CPO are examples of complex genetic traits. There exists sufficient evidence to hypothesize that disease loci for CL/P and CPO can be identified by a candidate-gene linkage-disequilibrium (LD) strategy. Candidate genes for clefting, including TGFA, BCL3, DLX2, MSX1, and TGFB3, were screened for LD with either CL/P or CPO in a predominantly Caucasian population, with both case-control- and nuclear-family-based approaches. Previously reported LD for TGFA with both CL/P and CPO could not be confirmed, except in CL/P patients with a positive family history. Also, in contrast to previous studies, no LD was found between BCL3 and either CL/P or CPO. Significant LD was found between CL/P and both MSX1 and TGFB3 and between CPO and MSX1, suggesting that these genes are involved in the pathogenesis of clefting. In addition, a mutation search in the genes DLX2, MSX1, and TGFB3 was performed in 69 CPO patients and in a subset of the CL/P patients. No common mutations were found in the coding regions of these genes; however, several rare variants of MSX1 and TGFB3 were found that may alter the latters' normal function. These results form the basis for future research, including (a) mutation searches in the MSX1 and TGFB3 genes in Caucasian CL/P patients and (b) extension of the search for MSX1 mutations in CPO patients to the noncoding regions.     

Wasp and bee venom allergy

To diagnose insect venom allergy a good patient history is important. Allergological tests (skin test, specific IgE titre) confirm the diagnosis. Patients are advised on preventive measures (e.g. with respect to clothing and use of perfume). They are also instructed on medical treatment (antihistaminics, epinephrine) in case they are stung again. In patients having had a serious systemic reaction immunotherapy should be considered. Immunotherapy leads to complete protection in more than 98% of patients with wasp (yellow jacket) venom allergy and in 75-80% of patients with bee venom allergy. Serious adverse reactions to immunotherapy are rare. Immunotherapy lasts at least 3 to 5 years. After cessation of immunotherapy the frequency of systemic reactions to the sting of a wasp or bee is in the range of 5-15%. There are insufficient data on the long-term effect of immunotherapy.     

Scrotal skin ulcer in a patient with a previous tonsillectomy because of natural killer cell lymphoma

The CD56+ lymphomas are a recently characterized high-grade malignancy of putative natural killer cell origin. They are mostly localized to the nasal areas but show a propensity to spread to or recur in the skin. We describe a unique case of CD56+ natural killer lymphoma that recurred in scrotal skin in a patient 8 years after an initial limited resection. Although this case was unusual in showing a prolonged period of apparent remission, it illustrated a characteristic clinicopathologic behavior of this rare tumor.     

Src can regulate carboxy terminal interactions with AFAP-110, which influence self-association, cell localization and actin filament integrity

The SH2 and SH3 binding partner AFAP-110 is a tyrosine phosphorylated substrate of Src. AFAP-110 has been hypothesized to link Src to actin filaments, which may contribute to the effects of Src upon actin filament integrity. However, it has been unclear what effect activated Src (Src527F) has upon AFAP-110 structure or function and whether AFAP-110 plays a role in actin filament integrity. We report here that the carboxy terminal 127 amino acids of AFAP-110 are comprised of an alpha-helical region that contains a leucine zipper motif. This indicated the potential of AFAP-110 to self-associate. Expression of the carboxy terminus as a fusion protein (GST-cterm) will permit affinity absorption of cellular AFAP-110. The integrity of the alpha-helical leucine zipper motif in GST-cterm is required for affinity absorption, but binding is not due to a classical leucine zipper interaction. Co-expression of Src527F, unlike cSrc, will abrogate affinity absorption of AFAP-110 with GST-cterm. These data indicate that Src527F has affected a change in the carboxy terminal structure that renders AFAP-110 unavailable for affinity absorption. Superose chromatography demonstrate that AFAP-110 will fractionate as a monomer or multimer, indicating AFAP-110 can be detected in a self-associated form in cell lysates. Co-expression of Src527F resulted in AFAP-110 fractionating with a molecular weight that predicts only a multimeric population. Deletional mutagenesis also indicate a biological role for the carboxy terminus in cellular localization and actin filament integrity. Deletion of the entire carboxy terminal alpha-helix (84 amino acids) will not permit AFAP-110 to efficiently colocalize with actin filaments or the cell membrane. Deletion of only the leucine zipper region of the carboxy terminal alpha-helix (44 amino acids) from AFAP-110 (AFAPAdeltazip) demonstrate that both AFAPdeltalzip and actin filaments are repositioned into rosette-like structures, similar to the effects of Src527F, while co-expression of AFAP-110 with cSrc will not affect actin filaments. These data indicate that AFAP-110 can play an important role in modulating actin filament integrity through carboxy terminal interactions that can be affected by Src527F.     

Segregation distortion in myotonic dystrophy

Myotonic dystrophy (DM) is an autosomal dominant disease which, in the typical pedigree, shows a three generation anticipation cascade. This results in infertility and congenital myotonic dystrophy (CDM) with the disappearance of DM in that pedigree. The concept of segregation distortion, where there is preferential transmission of the larger allele at the DM locus, has been put forward to explain partially the maintenance of DM in the population. In a survey of DM in Northern Ireland, 59 pedigrees were ascertained. Sibships where the status of all the members had been identified were examined to determine the transmission of the DM expansion from affected parents to their offspring. Where the transmitting parent was male, 58.3% of the offspring were affected, and in the case of a female transmitting parent, 68.7% were affected. Studies on meiotic drive in DM have shown increased transmission of the larger allele at the DM locus in non-DM heterozygotes for CTGn. This study provides further evidence that the DM expansion tends to be transmitted preferentially.     

Low prevalence of human papillomavirus in a geographic region with a high incidence of head and neck cancer

BACKGROUND: The main purpose of this study was to determine the prevalence of human papillomavirus (HPV) infection in patients with head and neck carcinomas from Brazil. MATERIALS AND METHODS: Forty-five patients with head and neck squamous cell carcinoma were included in the study, from 1995 to 1996. Forty-two were male and 3 female, with age ranging from 32 to 82 years (median 61). Five patients (11%) did not have previous history of use of tobacco and 38 (90.5%) were heavy smokers. Tumor sites were pyriform sinus, 10; tongue, 11 (oral, 6; base, 5); larynx, 7; floor of mouth, 3; tonsil, 6; retromolar area, 3; inferior gingiva 2; buccal mucosa, 2; and maxillary sinus in 1 patient. Twenty-five were stage IV, 17 stage III, and 3 stage II. RESULTS: The presence of HPV DNA was detected in 5 of 45 patients (11%), all of them with HPV 16. Two patients had HPV DNA in normal mucosa and tumor tissue, 1 patient had HPV DNA only in the normal mucosa and tumor tissue, 1 patient had HPV DNA only in the normal mucosa, and 2 patients were positive for HPV DNA in tumor tissue. Four patients were male and 1 was female; 2 patients were nonsmokers. Three patients had tonsil carcinoma, 1 patient had a tongue carcinoma, and 1 patient had a pyriform sinus cancer. CONCLUSIONS: The role of chemical carcinogens seems to be more important in the genesis of head and neck cancer than is HPV infection. The presence of HPV DNA in 5 of 45 patients stimulates further investigation to determine the role of HPV as a risk factor for head and neck carcinoma.     

Campylobacter enteritis in Johannesburg

In order to establish a reasonable protocol for a diagnostic laboratory we conducted a survey during which we confined the routine culture of stool samples for Campylobacter fetus to two groups--all infants under 2 years of age, and older children and adults with obviously diarrhoeic stools. Camp. fetus was isolated from 100 of 2323 stool specimens (4,3%). This is within the 3 - 8% isolation rates previously reported from surveys in which all specimens were cultured. Camp. fetus isolates represented 16,9% of all bacterial pathogens isolated, and Black infants showed a significantly greater isolation rate than White infants. We feel that culture for Camp. fetus is an essential part of any routine bacteriological investigation of diarrhoea. A partially selective culture policy for Camp. fetus will result in a recovery rate at least equal to that of Salmonella and enteropathogenic Escherichia coli.