Trisomy 1q43 syndrome: a consistent phenotype with macrocephaly, characteristic face, developmental delay and cardiac anomalies.

Trisomy 1q43 syndrome: a consistent phenotype with macrocephaly, characteristic face, developmental delay and cardiac anomalies: Patients with trisomy (1)(q42-qter) present with psychomotor retardation, macrocephaly, occasional presence of facial capillary naevi, cardio-vascular anomalies and small size for gestational age. We report on a girl with the same pattern of malformations, who has pure trisomy 1 q43: duplication of the region (1) (q43) and the translocation of the terminal region of the other chromosome 1 to the derivative 1, narrowing down the critical region for the characteristic traits of severe developmental delay, macrocephaly and congenital cardiac malformations.

Transient arterial occlusion raises enkephalin in the canine sinoatrial node and improves vagal bradycardia.

The C-terminal proenkephalin sequence, Methionine-enkephalin-arginine-phenylalanine (MEAP), is abundant in the myocardium and when delivered into the sinoatrial (SA) node by microdialysis, the peptide had significant vagolytic activity. The study that follows was conducted to determine if an increase in endogenous nodal MEAP could be demonstrated during reduced nodal blood flow and was endogenous MEAP similarly vagolytic. Microdialysis probes were placed in the canine SA node and perfused at 5 microl per min. The SA node artery was occluded and released four times at 10-min intervals. The intermittent occlusions were followed by one or two prolonged occlusions (30 min). Vagally mediated bradycardia was compared before, during, and after occlusion of the artery. An increase in recovered MEAP (70-220 fmol) was recorded during each of the initial 10-min occlusions. MEAP returned to baseline during each subsequent 10-min reperfusion. There was a sustained increase in MEAP (110-150 fmol) during longer occlusions. Contrary to the hypothesis, the increased MEAP during arterial occlusion was coincident with improved vagal bradycardia. The improvement in vagally mediated bradycardia was highly reproducible and was observed again during a second 30-min occlusion. The improved vagal function was reversed or reduced, respectively, when naltrindole or glibenclamide was included in the microdialysis inflow during arterial occlusion. Although these observations suggested that opioid receptors and ATP-sensitive K+ channels might have been involved, only a single dose of each agent was practical. Therefore, the specificity of these two responses remains to be confirmed. In summary, the recovery of endogenous opioids from the sinoatrial node increased during reduced arterial perfusion of the node. Contrary to expectations, the increase in recovered endogenous opioids was accompanied byimproved rather than impaired vagal bradycardia.

Delta opioid receptors inhibit vagal bradycardia in the sinoatrial node.

BACKGROUND: Methionine-enkephalin-arginine-phenylalanine (MEAP) is an endogenous opiate derived from the C-terminal sequence of the larger precursor molecule proenkephalin. This heptapeptide is abundant in the myocardium and has significant vagolytic activity when infused systemically. MEAP interrupted vagal bradycardia when it was delivered directly into the sinoatrial node by local microdialysis. This study was conducted to determine the opioid receptor responsible for the vagolytic effect of MEAP. METHODS AND RESULTS: Microdialysis probes were placed in the sinoatrial node of mongrel dogs and perfused at 5 microL/min. Increasing doses of MEAP were included in the nodal perfusate and approximately two thirds of the vagal bradycardia was inhibited with a maximal effect at 0.3 nmoles/microL and a half-maximal response near 0.1 nmoles/microL. When deltorphin II (a delta opioid receptor agonist) was infused into the sinoatrial node, more than 95% of the vagal bradycardia was eliminated at 0.3 nmoles/microL with the half-maximal response near 0.1 nmoles/microL, indicating that deltorphin II was more efficacious than MEAP. The maximal deltorphin II and MEAP effects were both similarly reversed by the paired infusion of increasing doses of the delta opiate receptor antagonist, naltrindole. Selected mu (endomorphin, super DALDA) and kappa (dynorphin, U50488) receptor agonists and mu (CTAP) and kappa (norBNI) receptor antagonists were completely ineffective in this system. CONCLUSIONS: These data suggest that the vagolytic effect of MEAP involves the activation of delta opiate receptors within the sinoatrial node.

Phenotypic features in a boy with monosomy 18 mosaicism.

We report on a patient with mosaicism for monosomy 18, a chromosomal abnormality that has been reported only once previously. The patient had cleft lip and palate and mild behavioral and academic problems. His phenotype was milder in comparison with the previously reported patient by Khalifa et al. [1996: Clin Genet 49:318-320]. Further case reports of this chromosomal anomaly will be needed to determine a consistent phenotypic pattern to assist in management and genetic counseling.

Effect of a Select Group of Seed Protectant Fungicides on Growth of Sclerotinia minor In Vitro and Its Recovery from Infested Peanut Seed.

Potato-dextrose agar containing 100 µg of streptomycin sulfate per milliliter of medium (SPDA) was amended to establish levels of 0, 2, 4, 6, 8, and 10 µg/ml of the fungicides thiophanate-methyl, carboxin, dicloran, captan, pentachloronitrobenzene (PCNB), or thiram. Fresh mycelial plugs, dry mycelial fragments, and sclerotia of Sclerotinia minor were placed onto the amended media, and mycelial growth and sclerotial germination were determined for 7 days. Thiophanate-methyl was the most effective chemical in inhibiting growth of S. minor, followed by PCNB and dicloran. Thiophanate-methyl was the only chemical that prevented germination of sclerotia of S. minor. Peanut seed naturally infested with S. minor was treated with the fungicides alone or in various combinations; control seed was treated with talcum powder. Seed was stored in polyethylene bags for 12 weeks at 24°C. To determine the incidence of viable S. minor in treated seed, seed was removed from bags, washed for 1 min in 0.2% unscented, liquid soap solution, rinsed twice in distilled water, and then dried for 15 min prior to plating on SPDA. The incidence of S. minor in talcum and thiophanate-methyl treated seed was 3.68 and 0.0%, respectively. Incidence of S. minor in seed treated with the other compounds ranged from 0.40 to 0.56%. Subsequent tests were performed using thiophanate-methyl and some of the above chemicals, in combinations or alone. These tests confirmed that thiophanate-methyl was the only compound that consistently reduced recovery of S. minor from infested seed. Germination of thiophanate-methyl treated seed equaled that of seed treated with talcum.

Autonomic control of heart rate in dogs treated chronically with morphine.

The vagotonic effect of chronic morphine on the parasympathetic control of the heart was examined in dogs treated with morphine for 2 wk. Because normal vagal function is critical to myocardial stability, the study was conducted to evaluate for potential impairments following chronic vagal stimulation. The hypothesis that persistent vagal outflow would result in a loss of vagal reserve and reduced vagal control of heart rate was tested. Heart rate and the high-frequency variation in heart rate (power spectral analysis) declined shortly after initiation of subcutaneous morphine infusion. A progressive bradycardia correlated well with the rising plasma morphine. The resting bradycardia (57 beats/min) was maintained through day 2 and was accompanied by a significant parallel increase in vagal effect and a decline in the intrinsic heart rate (160 vs. 182 beats/min). A compensatory increase in the ambient sympathetic control of heart rate was evident on day 2 and was supported by an increase in circulating catecholamines. The lowered intrinsic heart rate and elevated sympathetic activity were maintained through day 10 despite a return of the resting heart rate and plasma catecholamines to pretreatment values. These observations suggested that chronic morphine alters either the intrinsic function of the sinoatrial node or reduces the postvagal tachycardia normally attributed to nonadrenergic, noncholinergic agents. Both acute and chronic morphine depressed the rate of development of bradycardia during direct vagal nerve stimulation without altering the rate of recovery afterward. This last observation suggests that acute morphine reduces the rate of acetylcholine release. Results provide insight into the mechanisms that maintain vagal responsiveness. The results are also relevant clinically because opiates are increasingly prescribed for chronic pain and opiate abuse is currently in resurgence.

A peripherin/retinal degeneration slow mutation (Pro-210-Arg) associated with macular and peripheral retinal degeneration.

BACKGROUND: Mutations in the peripherin/retinal degeneration slow (RDS) gene have been identified in patients with retinitis pigmentosa and pattern macular dystrophy. The authors initially examined a large family affected with both peripheral and macular degeneration, inherited as an autosomal dominant trait. Screening for peripherin/RDS mutations identified a previously unreported nucleotide alteration in all of the affected individuals. Two additional families later were found to have this same mutation. METHODS: DNA samples from the members of three unrelated families were screened for peripherin/RDS mutations by denaturing gradient gel electrophoresis of the polymerase chain reaction-amplified peripherin/RDS coding sequences. The sequence change that was detected was further characterized by DNA sequencing. Family members were examined and evaluated with psychophysical and electrophysiologic methods. RESULTS: A proline to arginine mutation in codon 210 of peripherin/RDS was found in all clinically affected individuals. Macular changes included extensive geographic atrophy, pigment epithelial changes, and/or drusen. The proline to arginine mutation was not found among 100 healthy individuals, making it unlikely to be a nondisease-causing polymorphism. CONCLUSIONS: The authors identified a novel peripherin/RDS gene mutation associated with autosomal dominant retinal degeneration in patients from three different families. The largest family showed a broad variability in the expressivity of the mutation. The overlap of clinical features with those of age-related maculopathy highlights the need to consider photoreceptor-specific genes as potential factors in the etiology of the latter condition.

Medicare Transaction System: platform for change.

This article provides an overview of the Medicare Transaction System (MTS), a Health Care Financing Administration (HCFA)-wide initiative to be implemented starting in 1997 which will develop a national, standard, integrated, government-owned, contractor-operated Medicare claims processing system that will meet the challenges confronting Medicare over the next 2 decades. The authors discuss MTS goals and objectives, major features, how it will work, standardization efforts being undertaken in support of the initiative, contracting efforts involved, and project status.

The mouse intestinal fatty acid binding protein gene: nucleotide sequence, pattern of developmental and regional expression, and proposed structure of its protein product.

The rat intestinal fatty acid binding protein (I-FABP) gene has been used as a model to study temporal and spatial differentiation of the gut epithelium while its protein product has been used as a model for examining the atomic details of noncovalent fatty acid-protein interactions. We have isolated the mouse I-FABP gene (Fabpi) and determined its nucleotide sequence. Comparisons of the orthologous mouse, rat, and human I-FABP genes revealed three conserved domains in their otherwise divergent 5' nontranscribed sequences. RNA blot hybridization and multilabel immunocytochemical methods were used to compare the developmental stage-specific patterns of activation of the rat and mouse genes. In addition, Fabpi expression in enterocytes was examined as a function of their differentiation along the crypto-to-villus and duodenal-to-colonic axes of the small intestine. Based on the similar temporal and geographic patterns of mouse and rat I-FABP expression described here and the results of our earlier studies of transgenic mice containing rat Fabpi/human growth hormone fusion genes, we propose that one of the conserved domains, spanning nucleotides -500 to -419 in mouse Fabpi, and/or a 14-bp element, are necessary for establishing and maintaining its region-specific expression along the duodenal-to-colonic axis of the perpetually renewing gut epithelium. Finally, predictions of the structure of mouse I-FABP using the refined 2.0 A model of rat I-FABP, suggest that a proline found at position 69 of the mouse, but not rat, protein may affect its ligand binding properties.

Correlation between pathogenicity of Shigella and intraperitoneal survival in mice.

Phagocytosis of virulent and avirulent strains of Shigella and Escherichia coli in the mouse peritoneum was studied. A direct correlation between bacterial virulence and resistance to phagocytosis by peritoneal phagocytes was demonstrated. Virulent strains were less readily cleared and were able to multiply to a limited extent within the peritoneal cavity. An epimerase-deficient, rough mutant of S. flexneri 2a was highly susceptible to phagocytosis. Restoration of the cell wall structure in these mutants resulted in a significant increase in their resistance to phagocytosis. Susceptibility to phagocytosis in smooth S. flexneri was age-dependent. Cells from 16-hr cultures were more resistant to removal from the peritoneum than were cells from 48- and 72-hr cultures.