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.     

Autocrine inhibition of the epidermal growth factor receptor by intracellular expression of a single-chain antibody

A gene encoding a single-chain antibody which specifically binds the human epidermal growth factor (EGF) receptor has been constructed and expressed intracellularly. The single-chain antibody is derived from monoclonal antibody 225 which competes with EGF for binding to the extracellular domain of the receptor. The single-chain antibody was provided with a signal peptide to direct it to the secretory pathway and was expressed in EGF receptor transformed NIH/3T3 fibroblasts. EGF induced activation of its receptor was reduced in these cells. In addition, EGF-induced anchorage-independent growth of the cells was inhibited. The data suggest that the single-chain antibody functions in an autocrine fashion to inhibit the activity of the EGF receptor.     

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.     

Heat tolerance in Tuli-, Senepol-, and Brahman-sired F1 Angus heifers in Florida

We investigated heat tolerance and growth rate in two trials under ambient conditions in central Florida. Trial 1 (1994) involved 38 Brahman (B), 21 Senepol (S), 19 B x Angus (A), 20 S x A, and 20 Tuli (T) x A heifers. Trial 2 (1995) involved 13 A, 35 B, 30 S, 23 B x A, 17 S x A, and 28 T x A heifers. Measurements were made on three consecutive weeks during the hotter and cooler seasons of each year and included rectal temperature (RT, degrees C), respiration rate (RR, bpm), temperament score (TS; 1 = very docile, 5 = very aggressive), blood packed-cell volume (PCV), and plasma cortisol concentration (CORT). Data for RT were transformed (log10 [RT - 37]) before analysis. On the hottest date in Trial 1, log10 RT was not different between B (.39 +/- .011) and B x A (.37 +/- .016) or between T x A (.35 +/- .015) and B x A, but log10 RT was lower (P < .05) in S x A (.30 +/- .015) than in either S (.35 +/- .015) or T x A. On all dates in Trial 1, RR was lower (P < .05 to .001) and PCV was higher (P < .05 to .001) in B than in B x A. There were few differences in TS except on two dates when B scored higher (P < .01 to .001) than B x A, and these differences were associated with higher (P < .05) CORT in B than in B x A. Using initial BW as a covariate, adjusted ADG (kg) of T x A (.52 +/- .023) was not different from adjusted ADG of B x A (.57 +/- .024) or S x A (.54 +/- .023). On the hottest date in Trial 2, log10 RT and RR were higher (P < .001) in A (.59 +/- .017, 74 +/- 2.7) than in B (.47 +/- .010, 39 +/- 1.6), S (.42 +/- .011, 50 +/- 1.8), and crossbred heifers (.47 +/- .011, 60 +/- 1.8; .43 +/- .014, 55 +/- 2.4; and .50 +/- .012, 48 +/- 2.0 for T x A, S x A and B x A, respectively), and RR was higher (P < .001) in B x A than in B. On the coolest date in Trial 2, RR was slightly lower in B (32 +/- .5) than in A(34 +/- .7, P < .01) and B x A (36 +/- .6, P < .001) and was associated with higher PCV in B than in A. On both dates, TS and CORT were higher (P < .01) in B than in A. In Trial 2, adjusted ADG (kg) was higher (P < .01) in B (.43 +/- .017) than in A (.32 +/- .033), higher (P < .001) in S (.45 +/- .018) than in A, and higher (P < .001) in crossbreds (B x A [.53 +/- .023] + S x A [.44 +/- .025] + T x A [.46 +/- .019]) than in A. These data indicate that heat tolerance in F1 crosses of tropically adapted breeds (Tuli, Senepol, Brahman) with a temperate breed (Angus) is similar to heat tolerance displayed by purebred tropical breeds (Senepol, Brahman).     

Detection of coronary stenoses on source and projection images using three-dimensional MR angiography with retrospective respiratory gating: preliminary experience

OBJECTIVE: Our objective was to study the ability of three-dimensional MR angiography with retrospective respiratory gating to reveal stenoses in proximal coronary arteries on source and projection images. CONCLUSION: Proximal coronary artery stenoses can be identified using three-dimensional MR angiography with retrospective respiratory gating, both with projection images and on source images alone. Reasons for missed lesions included collateral vessels and retrograde flow distal to complete occlusion and volume averaging of vessels with adjacent structures. Causes of false-positive interpretations included small foci of decreased signal intensity distal to complete occlusion, partial volume effects on individual partitions, and regions of distal vessels leaving the imaging plane.