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Biomedical subjects

R J Smith

Publications and source records attributed to R J Smith.

At least 325 records · Page 18Linked to original sources

Induction of neutral proteinase and prostanoid production in bovine nasal chondrocytes by interleukin-1 and tumor necrosis factor alpha: modulation of these cellular responses by interleukin-6 and platelet-derived growth factor.

We have previously reported that recombinant human interleukin-1 (IL-1) stimulates matrix erosion in bovine nasal cartilage explants (R. J. Smith et al., Inflammation 13, 367-382, 1989). This action of IL-1 is believed to be caused by matrix-degrading neutral proteinases produced by activated chrondrocytes. Accordingly, we investigated the effects of recombinant human interleukin-1 alpha (IL-1 alpha), recombinant human interleukin-1 beta (IL-1 beta), and recombinant human tumor necrosis factor alpha (TNF alpha) on bovine nasal chondrocyte (BNC) responsiveness. IL-1 alpha and IL-1 beta stimulated a time (0-72 hr) and concentration-dependent (0.01-10 ng/ml) production of collagenase, gelatinase, caseinase, and prostaglandin E2 (PGE2) in BNC monolayer cultures. Neutral proteinase and PGE2 production by BNC was also induced by TNF alpha (0.2-200 ng/ml) in a time-dependent (0-72 hr) manner. Recombinant human interleukin-6 (IL-6) caused a concentration-dependent (6-200 ng/ml) potentiation of IL-1-stimulated neutral proteinase and PGE2 production by BNC. However, recombinant human platelet-derived growth factor homodimer BB suppressed BNC responsiveness to IL-1. A recombinant human IL-1 receptor antagonist protein inhibited BNC activation by IL-1 but not TNF alpha.

Animals↗

Preparation and stability of a radioiodinated pentamidine isethionate analog.

Iodopentamidine isethionate was heated for 70 min with [I-123]- or [I-125]-sodium iodide and ammonium sulphate in the absence of solvent at 140 degrees C. The product, [I-123]- or [I-125]-iodopentamidine isethionate, was purified by ion exchange chromatography. It was stable at room temperature in aqueous solution over several days, in human blood in vitro for at least 24 h (showing no binding to either cells or proteins), in urine over at least 15 h, and during nebulization in both ultrasonic and jet nebulizers.

Aerosols↗

The duration of orthodontic treatment.

Characteristics of the patient, the treatment plan, and the practitioner's office were examined to evaluate causes for variation in the duration of orthodontic treatment. From six offices 118 patients were evaluated. All patients were treated in a single phase with fixed appliances. Appliances were worn for an average of 23.1 months. The mean duration for offices ranged from 19.4 to 27.9 months. Thirty-eight percent of the patients had extractions, and 32% wore headgear. Fifty percent of the variation in treatment duration among patients was explained by a five-step multiple regression equation. The variables entering this equation were (1) number of extracted premolars, (2) number of broken appointments, (3) pretreatment mandibular plane angle, (4) pretreatment ANB angle, and (5) pretreatment Salzmann Index. Observations within each office suggested that the time spent by individual clinicians in detailed finishing, which would not be detected by measures such as the Salzmann Index, was an important source of unexplained variation in treatment duration.

Adolescent↗

Cephalometrics of anterior open bite: a receiver operating characteristic (ROC) analysis.

A new approach is presented for the evaluation of cephalometric measurements in which a measurement is considered to be a diagnostic test for the presence or the absence of some component of malocclusion. This approach allows cephalometric measurements to be judged by the criteria that are generally used for clinical diagnostic tests, including determination of sensitivities, specificities, positive and negative predictive values, and, most important, receiver operating characteristic (ROC) curves. In this study, ROC curves are generated for the relationship between several skeletal cephalometric measurements and anterior dental open bite in a sample of 1541 orthodontic patients. The overbite depth indicator is found to be a better diagnostic criterion for the presence of dental open bite than any other commonly used skeletal cephalometric measurement or ratio. ROC curves are of substantial value for evaluating the diagnostic information of cephalometric measurements.

Adolescent↗

Localization of the gene for branchiootorenal syndrome to chromosome 8q.

Branchiootorenal syndrome is an autosomal dominant disorder that affects an estimated 2% of profoundly deaf children. In addition to hearing impairment, it is characterized by a lop-ear deformity, preauricular pits, branchial cleft sinus tracts, and renal anomalies. The pathogenesis of the disease remains unknown; however, the defective gene has been localized to chromosome 8q by family linkage studies.

Abnormalities, Multiple↗

Localization of two genes for Usher syndrome type I to chromosome 11.

The Usher syndromes (USH) are autosomal recessive diseases characterized by congenital sensorineural hearing loss and progressive pigmentary retinopathy. While relatively rare in the general population, collectively they account for approximately 6% of the congenitally deaf population. Usher syndrome type II (USH2) has been mapped to chromosome 1q (W. J. Kimberling, M. D. Weston, C. Möller, et al., 1990, Genomics 7: 245-249; R. A. Lewis, B. Otterud, D. Stauffer, et al., 1990, Genomics 7: 250-256), and one form of Usher syndrome type I (USH1) has been mapped to chromosome 14q (J. Kaplan, S. Gerber, D. Bonneau, J. Rozet, M. Briord, J. Dufier, A. Munnich, and J. Frezal, 1990. Cytogenet. Cell Genet. 58: 1988). These loci have been excluded as regions of USH genes in our data set, which is composed of 8 French-Acadian USH1 families and 11 British USH1 families. Both of these sets of families show linkage to loci on chromosome 11. Linkage analysis demonstrates locus heterogeneity between these sets of families, with the French-Acadian families showing linkage to D11S419 (Z = 4.20, theta = 0) and the British families showing linkage to D11S527 (Z = 6.03, theta = 0). Genetic heterogeneity of the data set was confirmed using HOMOG and the M test (log likelihood ratio > 10(5)). These results confirm the presence of two distinct USH1 loci on chromosome 11.

Chromosome Mapping↗

Linkage studies of Usher syndrome type 1: exclusion results from the Usher syndrome consortium.

Usher Syndrome Type 1 is an autosomal recessive disease characterized by profound congenital hearing impairement and vestibular dysfunction followed by the onset of retinitis pigmentosa in childhood or early adolescence. Members of the Usher Syndrome Consortium, whose objective is to locate and isolate the genes for Usher syndrome, have pooled linkage data from 36 families with 111 affected individuals. We report the analysis of 206 blood group, protein, and DNA marker polymorphisms. No evidence of linkage heterogeneity among families was found for any of the markers studied; the negative lod scores exclude the locus for this disease from about 39% of the genome. Our results indicate the regions of the genome to which our continuing efforts should be directed.

Chromosome Mapping↗

Cephalometric changes during treatment with the open bite bionator.

Lateral cephalometric radiographs of 39 patients who were treated with an open bite bionator, also known as a "bionator to close the bite," were obtained from six private orthodontic practices. Comparisons of pretreatment cephalometric values with published standards indicate that clinicians do not generally use this appliance for patients who have marked excessive anterior vertical dimension. Rather, the cases appear to be Class II with mild anterior open bites or with some indication of open bite tendency, such as a steep mandibular plane angle. Changes in cephalometric values during treatment with the appliance were compared with normal growth standards. Patients exhibited a reduction in facial convexity and overjet, reduced eruption of maxillary molars, and less of an increase in facial height than expected. The appliance appears to be effective for Class II correction in patients who require control or improvement of moderately excessive vertical dimension.

Activator Appliances↗

Normal hearing in Splotch (Sp/+), the mouse homologue of Waardenburg syndrome type 1.

Splotch is considered a model of Waardenburg syndrome type I (WSI) because the abnormalities are caused by mutations in homologous genes, Pax-3 in mice and PAX3 (HuP2) in humans. We examined inner ear structure and function in Splotch mutants (Sp/+) and found no sign of auditory defects, in contrast to the deafness in many WSI individuals. The difference in expression of the genes in the two species may be due to different parts of the gene being mutated, or may result from variations in modifying influences as yet undefined.

Animals↗

Autosomal dominant branchio-oto-renal syndrome--localization of a disease gene to chromosome 8q by linkage in a Dutch family.

Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder with variable clinical manifestations affecting branchial, renal and auditory development. Varying clinical expression of the disease between different families suggests that multiple loci may be involved. However, the possibility of genetic heterogeneity as the cause of clinical variability cannot be resolved until the gene(s) causing BOR syndrome are mapped. DNA from four generations of a family with autosomal dominant BOR syndrome have been typed with a series of genetic markers on the long arm of chromosome 8. Using two point linkage analysis, a significant lod score of Z = 4.0 at theta = 0.05 was obtained with the D8S165 microsatellite marker. Multipoint analyses with 8q markers place the gene for BOR between the markers D8S87 and D8S165.

Abnormalities, Multiple↗

The effect of low-energy laser on skin-flap survival in the rat and porcine animal models.

Low-energy lasers are currently being used in the therapy of rheumatoid arthritis, chronic pain, muscle strain, and the promotion of wound healing in human and veterinary medicine. This study examined the effects of low-energy laser on skin-flap survival in a controlled interspecies study using the rat and porcine models. Twenty dorsal skin flaps based caudally were performed in 20 rats (10 laser-treated and 10 control flaps). The wounds were closed, and the flaps were sutured over the skin. Forty dorsal pig skin flaps based medially were raised in five pigs. The flaps were treated once per day for 10 days: 4 days preoperatively, the day of surgery, and 5 days postoperatively (30 s/cm3 per day). The average surviving rat flap surface area for the laser-treated flaps was 653 +/- 112 mm (mean +/- SD) and 580 +/- 60 mm in the control flaps, which was not significant (p greater than 0.05). In the porcine model, the average surviving area for the 20 laser-treated flaps was 949 +/- 174 mm, and the control average (n = 20) was 969 +/- 147 mm, also not significant. No beneficial effect was seen with low-energy laser preoperative and postoperative treatment of skin flaps in the rat and porcine models.

Animals↗

Evaluation of a microtiter plate fluorescent-antibody assay for rapid detection of human cytomegalovirus infection.

The use of monoclonal antibody (MAb) p63-27, which is reactive with the major immediate-early human cytomegalovirus (HCMV) protein pp72, was explored for the rapid diagnosis of HCMV viruria. The rapid assay detected all but 1 of 19 specimens identified by standard virus isolation methods from 1,676 newborn urine specimens, achieving a sensitivity of 94.5% and a specificity of 100%. The monoclonal antibody recognized 260 randomly obtained clinical isolates of HCMV, indicating the suitability of this reagent for use in screening assays. The sensitivity of the microtiter plate method declined rapidly for specimen from older infants and children with congenital CMV infection and virus-infected children attending a day-care center and was judged to be unacceptable for screening populations in this age group.

Antibodies, Monoclonal↗

Effect of pattern of aerosol inhalation on clearance of technetium-99m-labeled diethylenetriamine pentaacetic acid from the lungs of normal humans.

The clearance rate of inhaled aerosols of technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) from the lungs provides a rapid, clinically useful, noninvasive index of pulmonary epithelial permeability. In order to identify a method that minimizes intrasubject and intersubject variability and thereby provides a reliable means to identify patients with abnormal values, we administered a submicronic aerosol of 99mTc-DTPA to 10 healthy, nonsmoking male subjects with either tidal breathing (Vtidal) or multiple vital capacity maneuvers (VVC). Subjects then spontaneously breathed room air while counting continued for 30 min. Monoexponential clearance rates over 7, 15, and 30 min were compared with a two-compartment, biexponential analysis over 30 min. Intrasubject reproducibility was evaluated by repeating clearance 2 to 156 days later. Monoexponential clearance following VVC at 30 min equaled 1.36 +/- 0.55%/min compared with 0.83 +/- 0.25%/min for Vtidal (p less than 0.025). VVC inhalations resulted in a larger fast compartment of 16 +/- 12% compared with 3 +/- 2% with tidal breathing (p less than 0.01). The least intrasubject variability with coefficient of variation (CV) of +/- 18% was obtained with monoexponential analyses after Vtidal during 15 min of scanning and with either breathing maneuver over 30 min. Monoexponential clearance for 30 min with Vtidal gave the least scatter between subjects, with CV of +/- 30%. These data show that simple tidal inhalations of 99mTc-DTPA followed by a monoexponential analysis of the 30-min time-activity curve from both lungs minimize the degree of variability between and among subjects and provide a predicted normal value of clearance of 0.83 +/- 0.25%/min. The development of a more rapid curvilinear clearance followed by delivery VVC suggests that several deep breaths transiently increase epithelial permeability or reduce the volume of liquid in the alveolar subphase in some regions. Resting for 20 min prior to inhaling the aerosol of 99mTc-DTPA is recommended to avoid alterations in clearance rates from deep breathing.

Administration, Inhalation↗

Molecular biology in nutrition.

Recent progress in the field of molecular biology has had a considerable effect on both basic and applied clinical nutrition and offers even greater promise for the future. It is important for individuals working in clinical nutrition, as well as basic science investigators, to have an understanding of the fundamental concepts of molecular biology in order to be able to evaluate and apply new approaches to clinical problems as they become available. The purpose of this review is to provide those who are not molecular biologists with a brief overview of the fundamental concepts of molecular biology and then to describe a number of the recent applications of molecular biological methods and tools in the field of nutrition.

Animals↗

Changes in tyrosine phosphorylation of insulin receptors and a 170,000 molecular weight nonreceptor protein in vivo in skeletal muscle of streptozotocin-induced diabetic rats: effects of insulin and glucose.

The effects of experimental diabetes on in vivo tyrosine phosphorylation of the insulin receptor (IR) and non-receptor proteins were investigated in rat skeletal muscle. Diabetes was induced in male Sprague-Dawley rats (200 g) by streptozotocin administration (100 mg/kg, ip). Diabetic animals were subsequently anesthetized, insulin was injected via cardiac puncture, and hindlimb skeletal muscles were removed, frozen in liquid N2, and homogenized in sodium dodecyl sulfate. Tyrosine phosphoproteins were first immunoprecipitated and then identified by immunoblotting with antiphosphotyrosine antibodies. In both control and diabetic rats, insulin stimulated tyrosine phosphorylation of the IR beta-subunit and a major nonreceptor 170,000 mol wt (Mr) endogenous protein (pp170) in a dose- and time-dependent manner. Total IR number (determined by immunoprecipitation and immunoblotting with an anti-IR antibody) increased 2.4-fold in diabetic muscle, but there was little change in phosphorylated insulin receptor beta-subunit (157 +/- 12% of control value; P less than 0.001). In contrast, pp170 phosphorylation increased markedly in diabetes (500 +/- 119% of control value; P less than 0.005), and the time course of its disappearance was delayed compared to that in control rats. These changes were reversed by insulin therapy (5 U, sc, twice daily), but not by correction of hyperglycemia with phlorizin (0.4 g/kg.day, sc). In conclusion, in rat skeletal muscle in vivo, streptozotocin-diabetes results in 1) increased total IR number, 2) reduced efficiency of IR phosphorylation, and 3) markedly enhanced tyrosine phosphorylation of a 170,000 Mr putative IR substrate. Hypoinsulinemia, but not hyperglycemia, appears to increase the level of the phophorylated 170,000 Mr protein in streptozotocin-diabetes.

Animals↗