A progress report on the localization of Usher syndrome type II to chromosome 1q.
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Chromosome Mapping↗
Biomedical subjects
R J Smith
Publications and source records attributed to R J Smith.
Report on attempts to localize Usher syndrome type 1 by linkage analysis to selected candidate regions.
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Chromosome Mapping↗
Glucose transporter number, activity, and isoform content in plasma membranes of red and white skeletal muscle.
The fiber type composition of a skeletal muscle is an important determinant of its ability to take up glucose. Although numerous factors may account for this phenomenon, we have hypothesized that fiber type differences in glucose transporter number, isoform content, and/or intrinsic activity play an important role. Skeletal muscle plasma membranes were prepared from red and white gastrocnemius muscle from male Sprague-Dawley rats that were either exercised on a treadmill (1 h, 20 m/min, 10% grade), injected with 20 U insulin, or remained sedentary. In sedentary rats, plasma membrane glucose transporter number (cytochalasin B binding) was 2.4-fold greater in red compared with white muscle. Exercise and insulin both increased glucose transporter number by 40% in red muscle and twofold in white muscle. Maximal velocity of glucose transport (Vmax) was 2-fold greater in red compared with white muscle, whereas exercise and insulin increased Vmax by 2.3-fold in red muscle and 3.6-fold in white muscle. Glucose transporter turnover number, a measure of the average intrinsic activity of transporters in the plasma membrane, was not different between red and white muscle and increased 80-90% with exercise and insulin in both red and white muscle. Both GLUT-1 and GLUT-4 isoform content were greater in red than white muscle. These results suggest that fiber type differences in rates of glucose uptake in resting, insulin-stimulated, and contraction-stimulated skeletal muscle may be due to differences in the number but not the intrinsic activity of glucose transporter proteins.
Animals↗
Influence of dietary fiber on insulin receptors in rat intestinal mucosa.
This study was designed to determine the effect of dietary carbohydrate and fiber on mucosal insulin receptors, in order to correlate changes in cellular proliferation with hormonal responsiveness. In two protocols insulin binding was significantly affected by the consumption of dietary fiber. Compared to fiber-free, feeding corn bran increased binding in the duodenum 30% and ileum 50% but decreased binding in the jejunum 44%, and feeding guar gum increased binding in the colon 73% but decreased binding in the jejunum 40%. Feeding wheat bran or oat bran increased binding 50% in the small intestine compared to cellulose or fiber-free. Receptor autophosphorylation was 30% higher with fiber-free or wheat bran feeding than cellulose or oat bran. These changes in receptor binding and activity may correlate with altered rates of cell proliferation induced by dietary fiber.
Animals↗
Hemipelvectomy for trauma: case report.
This report documents a patient with an open pelvic fracture with gross contamination and partial avulsion of soft tissues with transection of femoral artery and vein, femoral nerve, and a stretch injury to the sciatic nerve. Initially, an attempt was made to treat with above-knee amputation, but due to massive soft tissue loss, this was not feasible. A left hemipelvectomy was done with closure of the wound. The patient required 14 units of blood. He was discharged and is now ambulatory with a prosthesis.
Adult↗
Effects of the sulfonylureas on muscle glucose homeostasis.
The sulfonylureas have pharmacologic effects both on insulin secretion by pancreatic beta cells and on responsiveness to insulin in peripheral tissues. The effects of the sulfonylureas on skeletal muscle may have a particularly significant influence on glucose homeostasis because of the important role of muscle as a peripheral site of glucose clearance. Under most physiologic conditions, the rate-limiting step for glucose utilization in muscle is its uptake across the plasma membrane; for this reason, the effects of the sulfonylureas on glucose transport have been a focus for study. In muscle tissue, the sulfonylureas appear to augment the stimulation of glucose uptake by insulin but not to alter glucose homeostasis in the absence of insulin. The mechanism of this effect, which requires several hours of exposure to a sulfonylurea, has not been defined. Although studies with cultured muscle cells have yielded inconsistent findings, recent work with the L6 rat skeletal muscle cell line demonstrated that the sulfonylureas exerted effects similar to those in muscle tissue both in time course and in requirement for co-stimulation by insulin. Mechanistic studies in L6 cells have shown that the sulfonylureas induce increased glucose transporter messenger ribonucleic acid levels and increased total cellular content of transporter proteins even in the absence of insulin, but that insulin is required for augmented glucose uptake activity. Based on these data, it has been suggested that insulin may cause the activation of transporters synthesized in response to sulfonylureas. The definition of the mechanism of this synergistic response to insulin and the sulfonylureas in L6 muscle cells may give insight into the in vivo molecular events involved in the action of the sulfonylureas in skeletal muscle.
Animals↗
Recurrent meningitis and Mondini dysplasia.
Three infants with cerebrospinal fluid otorrhea and recurrent meningitis due to Mondini dysplasia have been treated at Baylor College of Medicine, Houston, Tex; 39 other patients with this association have been described. This review highlights the characteristics and embryologic basis of the malformation. The clinical evaluation of an infant with recurrent meningitis is outlined, and the importance of brain-stem response audiometry and thin-cut computed tomography of the temporal bones is discussed. Surgical management depends on the functional status of the dysplastic ear; usually, a stapedectomy is performed and the vestibule is obliterated. Although the surgical failure rate is 30% after one procedure, early identification of the dysplasia and prompt surgical management diminish morbidity and mortality and permit early habilitation of the child with congenital hearing impairment.
Audiometry, Evoked Response↗
A comparative study of the fallopian canal at the meatal foramen and labyrinthine segment in young children and adults.
If entrapment is a critical factor in pathogenesis, the lower incidence of Bell's palsy in children compared with adults may have an anatomical basis. Histologic sections of 20 temporal bones from children younger than 2 years were examined to determine the diameter of the facial nerve and fallopian canal at the meatal foramen and in the labyrinthine segment. No statistically significant difference in the nerve/canal ratios in these areas was found. Comparisons were made with similar data from 10 adult temporal bones. The nerve/canal ratios in the labyrinthine portion were similar in both age groups; however, the ratio at the meatal foramen was significantly smaller in children. This may be due, in part, to growth of the vertical crest, which was found to increase considerably in length and width by adulthood. These results suggest that the facial nerve is not as tightly contained at the meatal foramen in children and provides a possible explanation for the relative infrequency of Bell's palsy in this age group.
Adolescent↗
Recombinant human granulocyte-macrophage colony-stimulating factor induces granule exocytosis from human polymorphonuclear neutrophils.
Exposure of human polymorphonuclear neutrophils (PMNs) to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) resulted in a time- and concentration-dependent (3-100 units/ml) extracellular release of a specific (vitamin B12-binding protein) but not azurophil granule constituent (myeloperoxidase). Negligible granule exocytosis occurred if PMNs were not preincubated with cytochalasin B prior to contact with GM-CSF. The extent of degranulation elicited with GM-CSF was reduced but not abolished when PMNs were incubated with EGTA in calcium-free medium. GM-CSF did not stimulate a rise in the cytosolic-free calcium concentration ([Ca2+]i), and it had no effect on PMN protein kinase C (PKC) activity.
Calcium↗
Current management of laryngeal and laryngotracheoesophageal clefts.
Laryngeal and laryngotracheoesophageal clefts (L-LTEC) are uncommon anomalies in neonates that cause significant morbidity secondary to aspiration, pneumonia, and respiratory distress. Other anomalies of development, such as esophageal atresia and tracheoesophageal fistula (EA-TEF), are observed in 20% of patients with L-LTEC and often confuse the radiographic and clinical picture. Repair of L-LTEC depends on the length and location of the cleft, associated anomalies, and concurrent systemic illness. For type I L-LTEC, endoscopic repair occasionally is possible with microsurgical instrumentation. With types II to IV L-LTEC, an open approach must be used. Tracheotomy is a universal requirement, often for extended periods of time. Reported here is our experience with four cases of L-LTEC managed over the past 7 years at Texas Children's Hospital.
Endoscopy↗
Glutamine prevents pancreatic atrophy and fatty liver during elemental feeding.
Rats fed an elemental, enteral diet (STD) developed pancreatic atrophy and hepatic steatosis following 60% jejunoileal intestinal resection. An isonitrogenous, isocaloric 2 g/100 ml glutamine-supplemented diet (GLN) significantly attenuated the development of pancreatic atrophy and hepatic steatosis associated with elemental feeding. Pancreatic weight, DNA, and protein were 27, 22, and 40% increased, respectively, in GLN animals. The pancreata of all animals appeared normal by light and electron microscopic examination. GLN animals had 12% less total liver wet weight, 3% less hepatic water content, and 47% less hepatic fat relative to STD rats. Histologic examination of the liver revealed extensive centrilobular fatty vacuolization in STD animals whereas GLN rats had normal looking hepatic parenchyma. Glutamine should be viewed as an important nutrient in elemental diets with trophic effects on the pancreas and protective effects against the development of hepatic steatosis.
Animals↗
Airway compression secondary to left atrial enlargement and increased pulmonary artery pressure.
Although congenital cardiac defects are infrequently considered a cause of major airway compression in neonates and infants, patients with left-sided cardiac enlargement can develop compression of the left mainstem bronchus. This is a consequence of the intimate relationship of the trachea and left mainstem bronchus to the left atrium, left pulmonary veins and left pulmonary artery. If the mean pulmonary arterial pressure, mean left atrial pressure and carinal angle are increased, the likelihood of major airway compression is high.
Airway Obstruction↗
Kinematics of the ulnar carpus related to the volar intercalated segment instability pattern.
Anatomic dissections were done on 18 fresh and 4 preserved cadaver upper extremities to study the pathology of the carpal kinetics and to define the ligaments involved in the volar intercalated segment instability pattern. In a normal wrist, the scaphoid, lunate, and triquetrum all rotate so that their distal surfaces tilt palmarward with radial deviation. With ulnar deviation, all three carpal bones rotate dorsally. In the volar intercalated segment instability pattern, the lunate remains tilted volarly instead of rotating dorsally with ulnar deviation. In this study changes in carpal motion were observed after serially sectioning the ligaments supporting the ulnar carpus before and after loads were applied to the wrist to simulate the dynamic conditions of the wrist. The ligaments were then repaired to help identify which repairs restored normal carpal motion with radial and ulnar deviation with and without axial loads. In these anatomic studies the volar intercalated segment instability pattern occurred when there was instability between both hamate and triquetrum and between the lunate and triquetrum. The main ligaments involved in this instability appeared to be the ulnar half of the volar arcuate ligament and the luno-triquetral ligament as division of these ligaments, particularly under axial loads, produced the most significant change in lunate rotation (p less than 0.05). Similarly repair of these two ligaments produced the most significant correction of lunate position particularly with maintenance of dorsal rotation of the lunate during ulnar deviation under axial loads (p less than 0.01).
Humans↗
Localization of Usher syndrome type II to chromosome 1q.
Usher syndrome is characterized by congenital hearing loss, progressive visual impairment due to retinitis pigmentosa, and variable vestibular problems. The two subtypes of Usher syndrome, types I and II, can be distinguished by the degree of hearing loss and by the presence or absence of vestibular dysfunction. Type I is characterized by a profound hearing loss and totally absent vestibular responses, while type II has a milder hearing loss and normal vestibular function. Fifty-five members of eight type II Usher syndrome families were typed for three DNA markers in the distal region of chromosome 1q: D1S65 (pEKH7.4), REN (pHRnES1.9), and D1S81 (pTHH33). Statistically significant linkage was observed for Usher syndrome type II with a maximum multipoint lod score of 6.37 at the position of the marker THH33, thus localizing the Usher type II (USH2) gene to 1q. Nine families with type I Usher syndrome failed to show linkage to the same three markers. The statistical test for heterogeneity of linkage between Usher syndrome types I and II was highly significant, thus demonstrating that they are due to mutations at different genetic loci.
Chromosome Mapping↗
Relationship between compliance by adolescent orthodontic patients and performance on psychological tests.
Two hundred and fifty-two adolescent orthodontic patients were categorized according to their general level of compliance during orthodontic treatment. Each patient completed three standardized psychological tests, (1) The Comprehensive Personal Assessment System: Self-Report Inventory, by Oliver H. Bown, (2) The Adolescent Alienation Index, by F. K. Heussenstamm, and (3) The Home Index, by Harrison Gough. The most important variable in predicting compliance was the sex of the patient. Females were more compliant than males. The psychological tests indicated that more compliant patients scored higher on self-esteem, derived self-satisfaction from personal achievement, were optimistic regarding the future, had higher socioeconomic status and had a low degree of general alienation from society. These easy-to-administer, brief psychological inventories could be helpful to clinicians in anticipating compliance problems during orthodontic treatment.
Adolescent↗
Safety of glutamine-enriched parenteral nutrient solutions in humans.
To determine the safety of glutamine-enriched parenteral nutrition, seven normal volunteers were admitted to the Clinical Research Center for three 5-d study periods. The subjects received infusions of parenteral nutrients containing increasing doses of glutamine (0, 0.285, and 0.570 g.kg body wt-1.d-1) substituted for alanine and glycine. Each study period was preceded by greater than or equal to 2 wk of normal food intake. The diets were isocaloric (1.2X estimated basal metabolic rate) and isonitrogenous (1.5 g protein.kg-1.d-1) with nonprotein calories given as dextrose (38%) and fat emulsion (62%). The diets were all well tolerated and there were no untoward effects. Plasma glutamine concentrations increased significantly with glutamine administration but plateaued at concentrations approximately 25% above control values. Ammonia and glutamate, potentially toxic metabolites of glutamine, did not change significantly with glutamine enrichment. Nitrogen balance and hormonal concentrations were unchanged during the three dietary periods. Results of mental-status examinations and continuous performance testing were normal and unchanged throughout the three periods. Glutamine-enriched parenteral nutrient solutions are well tolerated with no associated signs of toxicity in normal humans.
Adult↗
Molecular dosimetry of DNA adducts in Chinese hamster ovary cells and C3H10T1/2 mouse embryo fibroblast cells treated with benzo[a]pyrene.
Chromatographic profiles of DNA adducts formed following treatment of Chinese hamster ovary (CHO) cells or C3H10T1/2 mouse embryo fibroblast cells with benzo[a]pyrene (BP), in the presence or absence of rat liver S9 fraction, have been obtained by both direct labelling ([3H]BP) and 32P-post-labelling methods. The principal adduct formed in both cell lines was (+)-N2-(7R,8S,9R-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene- 10S-yl) 2'-deoxyguanosine (detected as its 3',5'-bisphosphate by 32P-post-labelling). In both cell lines significantly higher levels of adducts were observed in the presence of S9 fraction. The results of these studies provide useful reference data on the genotoxic metabolism of BP in these widely used cell culture systems and allow comparisons with data obtained in other experimental mammalian systems. Valid comparisons of metabolism in experimental systems used as extrapolative models for man are particularly important where multiple bioactivation pathways are possible, such as in the case of polycyclic aromatic hydrocarbons.
Animals↗
Assessment of rebreathing O2 consumption in humans with normal and diseased lungs.
We investigated sources of error in estimating steady-state O2 consumption (VO2ss) by calculating O2 uptake from an anesthesia bag containing O2, He, and N2 during 10-20 s of rebreathing (VO2rb). In 11 normal resting subjects, VO2rb calculated with end-tidal sampling overestimated VO2ss by 16 +/- 15% (SD) (P less than 0.003). This error was proportional to the increase in pulse rate during rebreathing, so that pulse-corrected VO2rb slightly underestimated VO2ss by 2.1 +/- 12.2% (P = 0.66) in the six subjects who rebreathed 28% O2 in the rebreathing bag but significantly underestimated VO2ss by 7.5 +/- 6.7% (P less than 0.04) in the six subjects who rebreathed 21% O2 in the rebreathing bag. During exercise, VO2rb underestimated VO2ss by 4 +/- 12% (P less than 0.001) and by 7 +/- 6% at O2 consumptions greater than 2,000 ml/min if O2 in the rebreathing bag was kept above 20% throughout rebreathing. We found that VO2rb calculated with end-tidal gas concentrations underestimated VO2ss by 1-43% in patients with moderate-to-severe obstructive lung disease, with even greater errors when mixed expired samples were used. The magnitude of the discrepancy correlated poorly with abnormalities in standard pulmonary function tests. Based on these data, VO2rb closely approximates VO2ss in normal subjects, provided hypoxia during rebreathing is avoided and cardiac acceleration from rebreathing is taken into account during resting measurement.
Adult↗