Contrasting patterns of nucleotide sequence variation at the glucose dehydrogenase (Gld) locus in different populations of Drosophila melanogaster

We have analyzed nucleotide sequence variation at the Glucose dehydrogenase (Gld) locus from four populations of Drosophila melanogaster from four continents. All four population samples show a significant reduction in silent variation compared to the neutral expectation. The levels of silent variation across all four populations are consistent with the predictions of the background selection model; however, Zimbabwe has a remarkably low level of variation. In the face of dramatically reduced silent polymorphism, an amino acid variant, leading to the common allozyme polymorphism at Gld, remains in low to intermediate frequency in all non-African samples. In the Chinese population sample, the ratio of replacement to silent variation is significantly elevated compared to the neutral expectation. The difference in patterns of variation across these population samples suggests that selection on Gld (or the Gld region) has been different in the Chinese population than in the other three.     

A mouse molecular mimic of human vascular adhesion protein-1

Human vascular adhesion protein-1 (VAP-1) is an endothelial sialoglycoprotein which exists in forms of Mr 90000 and 170000 and mediates lymphocyte binding to vessels under shear. VAP-1 is functionally defined by an inhibitory mouse mAb 1B2. A large-scale immunoaffinity purification of VAP-1 from human tonsil lysates was performed to determine the protein sequence for VAP-1 cDNA cloning. A dominant protein of molecular weight 90000 was obtained which yielded an N-terminal sequence of 20 amino acids which bore no significant identity to any protein sequence in the data banks. A mouse mAb (5B11) against a synthetic peptide from this sequence was raised and found to stain tissues in an identical manner to mAb 1B2, to inhibit lymphocyte adhesion to endothelial cells and to recognize VAP-1. Later, the N-terminal sequence obtained from the 1B2 immunoprecipitations was found to be identical to a mouse cyclophilin C associated protein (mCyCAP) subsequently published by others. We show here by several criteria at the protein and DNA level that VAP-1 is distinct from mCyCAP. Moreover, we elucidate the mechanism which results in binding of mCyCAP to mAb 1B2 during antibody synthesis in hybridoma cells and the sequelae of co-precipitation of mCyCAP during the immunoaffinity chromatography. Binding of mCyCAP to a mouse mAb has not been described before and suggests a new function for this molecule in immunoglobulin synthesis and/or secretion. Moreover, these data indicate that the N-terminal peptide of mCyCAP is a molecular mimic of a functionally important epitope of VAP-1.     

Anxious children: coping in dental practice

Treating anxious children is a challenge that many dentists face. Not only do anxious children find it difficult to cope with dental treatment but dentists also find it difficult to cope with anxious children. This article is intended to simplify the management of anxious children in general dental practice. Behavioural management, the coordination of the whole dental team, treatment planning and the use of inhalation sedation will be discussed.     

Bis-chloromethyl ether and carcinogenesis of alkylating agents

Bis-Chloro-Methyl-Ether is an alkylating agent and a recognised carcinogen. It can form spontaneously from the reaction of chloridric acid with formaldehyde. In the past it was extensively used as a chemical intermediate in organic synthesis, particularly as a crosslinking agent in the manufacture of ion-exchange resins. Recently, since its carcinogenicity has been proved in animal studies and confirmed in epidemiological studies of occupationally exposed cohorts, its use has been consistently reduced. A characteristic association has been observed between BCME exposure and a peculiar lung cancer histotype (oat cell carcinoma). In spite of these data, little information is available on the molecular alterations related to BCME exposure and possibly to its carcinogenic activity. Some suggestions can reasonably be obtained considering how the class of alkylating agents acts. They form adducts, binding different positions of DNA bases. The reaction that seems more relevant for mutagenesis and carcinogenesis is the alkylation at the atom O6 of guanine in DNA, which is followed by mis-coding and GC-->AT transition mutation. This kind of alteration determines the activation of a group of enzyme like DNA repair, mismatch repair, excision repair and a specific one, methyl guanine methyl transferase (MGMT). This last repair protein transfers alkyl groups from the O6 position of guanine to an internal cysteine residue, inactivating itself. Thus, the possibility for the cell to eliminate alkylated DNA bases depends strictly upon the cellular content of MGMT. In this view reduced or absent levels of the enzyme are associated with an increased number of adducts and hence increased risk of DNA mutations and cancer. At the moment no molecular studies in vivo have been performed to verify this hypothesis. The peculiar association BCME-oat cell carcinoma, the most chemosensitive tumor, need further investigation.     

7-OH-DPAT has d-amphetamine-like discriminative stimulus properties

A fluorometric procedure has been developed for detection and estimation of laccase activity in fungal broth cultures. Laccase solution was pretreated with catalase for 1 h at 37 degrees C and pH 5. Homovanillic acid was then added and the reaction mixture incubated for a further hour at 37 degrees C. The fluorescence was then developed by addition of 0.1 M glycine buffer at pH 10. Laccase preparations from Pyricularia oryzae, Coriolus hirsutus and Pycnoporus cinnabarinus catalysed formation of a fluorescent product of HVA but the optimum pH values of enzyme activities varied. The culture fluids of several other fungi also catalysed development of fluorescence in solutions containing HVA. p-Hydroxyphenylacetic acid was a poor substrate for all laccases in vivo except that produced by Perennipora tephropora.     

Gait adaptations before and after anterior cruciate ligament reconstruction surgery

Gait analyses of rehabilitated individuals with anterior cruciate ligament (ACL) deficiency and reconstruction have identified the final adaptations of increased hip extensor torque and hamstring electromyography (EMG) and decreased knee extensor torque and quadriceps EMG during stance. The initial adaptations to injury and surgery are, however, unknown as are the factors that influence the development of the adaptations. Identification of the initial response to injury would provide a basis for determining whether the final adaptations are learned automatically or if they are the result of a lengthy training period in which various factors may affect their development. The purpose of the study was to evaluate the initial effects of ACL injury and reconstruction surgery on joint kinematics, kinetics, and energetics, during walking. Injured limbs from nine subjects with ACL injury were tested 2 wk after injury, and 3 and 5 wk after surgery. Ten healthy subjects were tested. Kinematic and ground reaction data were collected and combined with inverse dynamics to calculate the joint torques and powers. A knee extensor torque throughout most of stance was observed in the injured limbs at all test sessions. This result was in conflict with previous observations of reduced extensor torque or a flexor torque in rehabilitated patients with ACL reconstruction and patients with ACL deficiency. This result also differed from the typical midstance extensor then flexor torque in healthy control subjects. Trend analysis showed a significant (P < 0.001) change in average position at the hip and knee, extensor angular impulse at the hip, and positive work done at the hip 3 wk after surgery followed by a partial rehabilitation at 5 wk after surgery. Power and work produced at the knee were reduced fivefold (P < 0.001) after 5 wk of rehabilitation and did not recover to pre-surgical levels. The existence of a long-lasting knee extensor torque 2 wk after injury indicated that the adaptation process to ACL deficiency is lengthy, requiring many gait cycles, and that numerous factors could be involved in learning the adaptations.     

Vitrectomy for retained lens fragments after phacoemulsification

PURPOSE: Posterior lens fragments after phacoemulsification can be a serious complication of cataract surgery. This study is designed to evaluate the clinical features of eyes after pars plana vitrectomy has been performed to remove posteriorly dislocated lens fragments after phacoemulsification. METHODS: The authors performed a retrospective chart review of 126 consecutive eyes of 126 patients with dislocated lens fragments after phacoemulsification, managed with pars plana vitrectomy at Associated Retinal Consultants of Michigan. These eyes were operated on from January 1986 through January 1996. RESULTS: The relation of the intervals between cataract surgery and vitrectomy to various postoperative clinical parameters was studied. Clinical features at presentation included elevated intraocular pressure (IOP over 25 mmHg) in 52.4% of the eyes, uveitis in 69.6%, and corneal edema in 50.8%. Initial visual acuity was 20/400 or worse in 73.8% of the eyes. The mean preoperative visual acuity was 20/278 (median, 20/400), whereas the mean final visual acuity was 20/40 (median, 20/50) after a mean follow-up of 18.9 months. Retinal detachments were found in 20 eyes: 7 before vitrectomy and 13 during or after it. After surgery, 44% of eyes achieved a final visual acuity of 20/40 or better and 90% were 20/400 or better. The distribution of best-corrected final visual acuities among the eyes showed statistically significant differences based on the type of intraocular lens (IOL) used, with posterior chamber IOL greater than anterior chamber IOL, and anterior chamber IOL greater than aphakia. Reasons for a poor visual outcome included persistent corneal edema (four eyes), retinal detachment (two eyes), central retinal vein occlusion (two eyes), age-related macular degeneration (two eyes) glaucoma (one year), and endophthalmitis (one eye). CONCLUSIONS: There were no statistically significant differences between early (< 7 days) and delayed (8 days or more) vitrectomy when increased IOP, corneal edema, choroidal effusions, cystoid macular edema, and visual acuity were analyzed. The use of vitrectomy to remove posteriorly dislocated lens fragments has been shown to be an effective treatment method that significantly reduces the inflammatory response and hastens visual recovery.