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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 613 records · Page 34Linked to original sources
PubMed1994

The role of xanthine oxidase and xanthine dehydrogenase in skin ischemia.

The importance of sequential events which lead to skin necrosis has significant implications in trauma, vascular injury, and wound healing. In this series of experiments, we tested the hypothesis that xanthine oxidase (XO) activity was increased along an ischemic gradient of a skin flap and that the XO enzyme activity correlated with an increase in neutrophils. There were two animal groups in which the skin flaps were raised and assayed at 0, 1, or 6 hr. In the other group, they were created as bipedicle flaps for 7 days, before the distal attachment was divided and the tissue assayed. In the acutely raised flaps, some animals were treated with the XO inhibitor, allopurinol. Xanthine dehydrogenase (XD) and XO activity was measured with a fluorometric pterin assay and neutrophil concentration was measured using a myeloperoxidase marker. In this model, there was consistent skin necrosis in the distal end of the skin flap (48 +/- 8%). The data showed that both XD and XO activity in the distal ends was statistically significantly increased over the sham control or proximal ends of the skin flaps at 1 hr (P < 0.05). XO activity remained elevated in the distal ends at 6 hr. Allopurinol significantly reduced the neutrophil concentrations in the distal ends of the skin flaps when compared to untreated animals (P < 0.05). Moreover, allopurinol reduced skin necrosis to 12 +/- 1%. Preconditioning of the skin flap reduced the XO activity to sham control levels. The observations implicate XO activity as source of free radical injury in skin necrosis seen in random skin flaps.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol↗
PubMed1994

Effect of chronic lithium treatment with or without haloperidol on number and sizes of neurons in rat neocortex.

The present study used stereological methods to determine whether long-term administration of lithium, with or without haloperidol, affects the number and average volume of neocortical neurons. Twenty-five rats were divided into three groups and given no treatment, lithium, or lithium combined with haloperidol. Serum lithium levels ranged from 0.5 to 0.8 mmol/l. Haloperidol was injected intraperitoneally at a daily dose of 1 mg/kg. After 30 weeks of treatment, the animals were killed and the brains were prepared. Neocortical volume, density of neurons, total number of neurons and mean volume of neurons were estimated. As no differences were found between the groups, the present study provides no evidence for quantitative morphological changes in the cerebral cortex due to long-term 'therapeutic' levels of lithium, with or without haloperidol.

Animals↗
PubMed1994

SDZ 208-911, an amino-ergoline with partial dopamine agonist properties, dose dependently increases cocaine self-administration in the rat.

Brain dopamine neurotransmission appears to be an important component of the neural pathways involved in the maintenance of intravenous (IV) cocaine self-administration in rats. The effects of a novel partial dopamine agonist, SDZ 208-911, on intravenous cocaine self-administration in rats was studied. SDZ 208-911 at a dose range of 0.025-1.6 mg/kg SC dose-dependently increased the number of lever presses and drug intake in rats exposed to limited (3-h) daily access to cocaine on a continuous reinforcement schedule (0.75 mg/kg per injection). This behavioral profile is similar to that observed following administration of dopamine antagonist drugs and has been hypothesized to reflect a compensatory increase in drug intake due to a reduction of the reinforcing efficacy of the drug, probably because of functional antagonism at the receptor site. These results suggest that dopamine partial agonists may act as functional dopamine antagonists in the face of pharmacologically induced activation of brain dopamine function.

Animals↗
PubMed1994

Cytogenetic and fluorescence in situ hybridization studies on sporadic and hereditary tumors associated with von Hippel-Lindau syndrome (VHL).

We performed cytogenetic and fluorescence in situ hybridization (FISH) studies on 29 sporadic or familial tumors associated with von Hippel-Lindau [correction of Landau] disease. Four of five renal cell carcinomas with detectable alterations showed clones with chromosome 3 alterations. These changes led to loss of genetic material visible with cytogenetic resolution: either an unbalanced translocation involving 3p or loss of a whole homolog 3, resulting in monosomy of 3p. We have previously mapped the VHL gene to chromosomal region 3p25-p26. We applied FISH using the single copy probes cA233 and cA479, sequences close to the VHL gene, in a search for submicroscopic deletions of 3p. Use of FISH with differentially labeled probes indicated cA479 to be distal to cA233, but both were located within bands 3p25-26. FISH with single copy probes for interphase cytogenetics detected four subclones with deletions in the VHL region in 8/22 tumors, including four tumors which appeared cytogenetically normal. FISH proved to be a powerful tool in tumor genetic studies, especially helpful in detecting tumor subclones in benign and slowly growing tumors.

Adrenal Gland Neoplasms↗
PubMed1994

Free and island vascularized joint transfer for proximal interphalangeal reconstruction: a series of 27 cases.

Twenty-seven vascularized joints were transferred in 26 patients for proximal interphalangeal joint reconstruction: 7 heterodigital island, 7 homodigital island (distal to proximal interphalangeal), 2 free heterodigital, and 11 free second toe proximal interphalangeal. With a mean follow-up period of 37 months, mean active range of motion of heterodigital island joint was 56 degrees (mean extensor lag, 21 degrees), excepting one failure ending with an arthrodesis. Four complications occurred in the homodigital island joint series: one sepsis, one nail dystrophy, one failed distal arthrodesis, and one bone abutment in flexion. Excluding the sepsis, mean active final range of motion was 52 degrees after a mean follow-up period of 18 months. The two free heterodigital joints had 80 degrees and 65 degrees of motion. The worst results occurred in the free second toe proximal interphalangeal joints transferred, with a mean active range of motion of 33 degrees (mean extension lag 39 degrees). The main advantages of these techniques are a compound tissue transfer, rapid bone healing, good lateral stability, growth potential, and long-term cartilage preservation.

Adult↗
PubMed1994

Reconstruction of urinary and gastrointestinal tracts in total pelvic exenteration: experience at Columbia-Presbyterian Medical Center.

OBJECTIVES: To examine the effectiveness of and complications from total pelvic exenteration (TPE) with maintenance of urethral and anal sphincter function for locally invasive tumors of the pelvis. METHODS: A retrospective review of 4 patients who have undergone TPE with urethral and anal sphincter preservation at Columbia-Presbyterian Medical Center in the last 2 years was performed with attention to perioperative morbidity and mortality, disease-free status, and need for further operative procedures. RESULTS: Two patients had colorectal adenocarcinoma, 1 had squamous cell carcinoma of the cervix, and 1 had prostate sarcoma. All had urinary tract reconstruction with orthotopic neobladder creation, and 3 of 4 had primary low rectal anastomoses for gastrointestinal reconstruction. One patient underwent creation of a J rectal pouch. One of 4 patients had received radiation therapy for the disease prior to surgery. There was no operative or perioperative mortality. Two of 4 patients required reoperation, 1 in the immediate postoperative period for repair of a left ureteral stricture, and the other 13 months postoperatively for repair of a rectal-neobladder fistula. With a mean follow-up of 25 months (range, 21 to 43 months), 3 of 4 patients are alive and free of disease. All living patients are continent of urine and 2 of 3 are continent of stool. CONCLUSIONS: Our experience confirms that TPE can be effective in controlling a variety of locally advanced pelvic tumors and can be performed in conjunction with simultaneous genitourinary and gastrointestinal reconstruction with minimal morbidity.

Adenocarcinoma↗
PubMed1994

Tobacco, alcohol and other drug use among college students.

Smoking, binge drinking, and illicit drug use remain common among college students. The purpose of this study was to characterize college students who smoke, and to determine the relationship between smoking behavior and alcohol and illicit drug use. Cigarette smoking, alcohol use and illicit drug use practices were surveyed at ten public colleges in Virginia. A total of 3,374 undergraduate respondents from eight schools (those with response rates > 20%) were analyzed. The one-year smoking prevalence was 23.5%. Smokers were significantly more likely to be white, female, and to have lower life satisfaction and grade point averages than nonsmokers. Students classified themselves as regular or occasional smokers. Smoking was significantly associated with binge drinking in the last two weeks and with marijuana, cocaine, and LSD use in the past year. Except for binge drinking, the associations were stronger for regular than for occasional smokers. Cigarette smoking, even occasional use, identifies a subgroup of college students who are at increased risk of binge drinking and illicit drug use. This information may be useful in developing targeted drug prevention programs.

Adolescent↗
PubMed1994

Vitamin B-6 deficiency vs folate deficiency: comparison of responses to methionine loading in rats.

The plasma homocysteine response to methionine loading was assessed in vitamin B-6- and folate-deficient rats. Rats fed vitamin B-6- or folate-deficient diets for 4 wk were administered a gastric gavage of methionine (100 mg/kg body wt). Subsequent plasma analyses revealed a peak post-methionine load increase in plasma homocysteine concentration of > 300 mumol/L in the vitamin B-6-deficient rats. Folate-deficient rats exhibited no significant changes in plasma homocysteine after the load. These disparate responses can be explained by the observed increase in hepatic S-adenosylmethionine (SAM) concentration because of the load. In vitamin B-6 deficiency, increased SAM inhibits homocysteine remethylation, which, in conjunction with the impaired homocysteine catabolism due to the deficiency and the increased synthesis of homocysteine due to the methionine load, leads to a large elevation of homocysteine in the blood. In folate deficiency, increased SAM activates homocysteine catabolism, which compensates for the increased synthesis of homocysteine due to the load and thus no change in blood homocysteine is observed. These results have significant bearing on the interpretation of both positive and negative responses to methionine loading in humans.

Animals↗
PubMed1994

Dietary fat saturation affects apolipoprotein gene expression and high density lipoprotein size distribution in golden Syrian hamsters.

Our purpose was to elucidate the mechanisms whereby diets high in polyunsaturated fat lower plasma triglycerides and HDL cholesterol concentrations compared with diets high in saturated fat. Twenty-four male Golden Syrian hamsters (F1B strain) were fed semipurified diets containing 0.2 g cholesterol + 15 g fat/100 g diet enriched (13 g/100 g) in either coconut oil or soybean oil for 18 wk. Consumption of the soybean oil diet was associated with significantly (P < 0.001) lower mean concentrations of HDL cholesterol (28%), triglycerides (51%) and free fatty acids (51%), as well as a significantly lower proportion of large HDL particles. No effect on plasma cholesteryl ester transfer protein or lecithin:cholesterol acyltransferase activities or hepatic or intestinal apolipoprotein (apo) A-I, A-IV or E mRNA levels were noted. The soybean oil-fed group had significantly lower levels of mRNA (P < 0.05) for hepatic apo A-II (23%) and apo C-III (18%) and significantly higher levels of mRNA for intestinal apo C-II (23%). Our data are consistent with the hypothesis that diets high in polyunsaturated fatty acids lower triglyceride concentrations in hamsters by decreasing apo C-III gene expression and by increasing apo C-II gene expression. In addition, reduced expression of apo A-II in animals fed the soybean oil diet may contribute to the lower HDL cholesterol concentration and larger proportion of small HDL particles noted.

Animals↗
PubMed1994

Severe folate deficiency causes secondary depletion of choline and phosphocholine in rat liver.

It has previously been shown that choline deficiency causes depletion of hepatic folate concentration in rats. Two separate experiments were undertaken to investigate the converse phenomenon: whether folate deficiency would lead to depletion of hepatic choline. In Experiment 1, severe folate deficiency was induced in rats by feeding an amino acid-defined diet containing (per kg diet) 1.4 g choline, 0 mg folate and 10 g succinylsulfathiazole. Control rats were fed the same diet containing 8 mg folate/kg. After 4 wk, plasma and hepatic folate concentrations were significantly depleted in the severely folate-deficient rats compared with controls (P < 0.001), and hepatic choline and phosphocholine concentrations were 65 and 80% lower, respectively (P < 0.001). In Experiment 2, moderate folate deficiency was induced in rats by feeding the same diet as described above, but with the succinylsulfathiazole omitted. After 24 wk, significant systemic folate deficiency was present in the moderately folate-deficient rats compared with controls (P < 0.001). A modest reduction (36%, P = 0.087) in hepatic choline concentration was observed in the moderately folate-deficient rats compared with controls. No significant differences in hepatic phosphocholine concentrations were detected between the two groups. These results indicate that severe folate deficiency causes secondary hepatic choline deficiency in rats.

Animals↗
PubMed1994

Patterns of differentiation and hybridization in North American wolflike canids, revealed by analysis of microsatellite loci.

Genetic divergence and gene flow among closely related populations are difficult to measure because mutation rates of most nuclear loci are so low that new mutations have not had sufficient time to appear and become fixed. Microsatellite loci are repeat arrays of simple sequences that have high mutation rates and are abundant in the eukaryotic genome. Large population samples can be screened for variation by using the polymerase chain reaction and polyacrylamide gel electrophoresis to separate alleles. We analyzed 10 microsatellite loci to quantify genetic differentiation and hybridization in three species of North American wolflike canids. We expected to find a pattern of genetic differentiation by distance to exist among wolflike canid populations, because of the finite dispersal distances of individuals. Moreover, we predicted that, because wolflike canids are highly mobile, hybrid zones may be more extensive and show substantial changes in allele frequency, relative to nonhybridizing populations. We demonstrate that wolves and coyotes do not show a pattern of genetic differentiation by distance. Genetic subdivision in coyotes, as measured by theta and Gst, is not significantly different from zero, reflecting persistent gene flow among newly established populations. However, gray wolves show significant subdivision that may be either due to drift in past Ice Age refugia populations or a result of other causes. Finally, in areas where gray wolves and coyotes hybridize, allele frequencies of gray wolves are affected, but those of coyotes are not. Past hybridization between the two species in the south-central United States may account for the origin of the red wolf.

Alleles↗
PubMed1994

Is there a relationship between autoantibodies and silicone-gel implants?

The present study was conducted to determine if 200 patients with silicone-gel implants demonstrated elevated levels of autoantibodies, compared with a similar group of 100 age-matched control subjects without breast implants. These results were then compared with 29 patients who had demonstrated implant rupture. Differences in the frequency of autoantibody levels were determined by the chi-squared test. Differences in autoantibody titers were determined by Wilcoxon's signed rank test. Differences were considered significant with p > 0.05. The prevalence of a positive antinuclear antibody (ANA) test (dilution 1:100) in the 200 patients with breast implants was 26.5% compared with 28% in the 100 control subjects. In 29 patients with implant rupture, only 17.2% tested ANA positive. These values were not significantly different. In addition, there were no significant differences between the ANA titers of positive patients in each group. In each of the three groups, all patients who tested ANA positive were analyzed to assess the frequency and titer of other autoantibodies, including anti-DNA, anti-cardiolipin, anti-SSA, anti-SSB, anti-SM, anti-RNP, and anti-Scl-70. There were no significant differences between the frequency or titer of any of these autoantibody levels in each of the three groups of patients. These studies strengthen the concept that there is no conclusive evidence that silicone-gel implants are related to the development of connective tissue disease.

Adult↗
PubMed1994

Factors affecting the rupture of silicone-gel breast implants.

Between January 1990 and April 1993, over 500 patients with silicone-gel breast implants were clinically assessed regarding their implant status. Of these, 57 patients requested implant removal. Reasons for removal were capsular contracture (39 patients), possible implant rupture, suggested by ultrasound testing or mammography (7 patients), "silicone phobia" (7 patients), and asymmetry (4 patients). Of the 102 implants that were removed, 60% were intact, 33% were ruptured, and 7% were leaking. There was a positive correlation between duration of implantation time and the number of ruptured and leaking implants. Of the 45 implants that had been in place for 5 years or less, 93% were intact. Of the 29 implants that had been in place for 6 to 10 years, only 31% were intact (59% were ruptured and 10% were leaking). Similar results were obtained in 20 implants after 11 to 15 years (30% were intact, 55% were ruptured, and 15% were leaking). Of 8 implants that were in place for 16 to 26 years, 50% were intact and 50% were ruptured. In this study, the integrity of breast implants was not related to the degree of capsular contracture.

Adult↗
PubMed1994

The pathophysiological changes in the bladder obstructed by benign prostatic hyperplasia.

None of the hypotheses to explain the genesis of obstructed detrusor instability covered in this report provide a satisfactory explanation, by themselves, for the condition. While symptoms associated with prostatic obstruction are a common cause of patient referral to a urologist, all therapeutic advances so far have been directed towards the relief of bladder outflow resistance. It is possible that pharmacotherapy, for example, with drugs which stabilize muscle cell membranes and autonomically active drugs such as alpha 1-antagonists, possibly combined with anticholinergics, will have a therapeutic role in the treatment of obstructive detrusor instability. Further studies of obstructed human bladder are necessary to investigate the importance of changes in receptor density, affinity and distribution, agonist release and degradation and subsequently the ultrastructural and physiological alterations following the relief of obstruction.

Adult↗
PubMed1994

Characterization of a cleavage mutant of the measles virus fusion protein defective in syncytium formation.

Membrane fusion caused by measles virus (MV) is a function of the fusion (F) protein. This process is essential for penetration into the host cell and subsequent initiation of the virus replicative cycle. The biological activity of the MV F protein is generated by endoproteolytic cleavage of a precursor protein (F0) into a large F1 subunit and a smaller F2 subunit held together by disulfide bonds. The cleavage site consists of a cluster of five basic amino acids (amino acids 108 to 112) within the predicted primary structure of the F protein. To investigate the role of the arginine residue at the carboxy terminus of the F2 subunit (arginine 112), site-directed mutagenesis was used to construct a cleavage mutant of the MV F protein in which this arginine residue was changed to a leucine residue. The mutated F gene, encoding four out of the five basic amino acids at the cleavage site, was inserted into the genome of vaccinia virus. The resulting recombinant virus was used to study expression of the mutant F protein in infected cells. Analysis of the Leu-112 mutant protein made in infected cells demonstrated that this single-amino-acid substitution resulted in a reduced rate of transport of the mutant protein to the cell surface, despite its efficient cleavage to yield F1 and F2 subunits. However, the electrophoretic mobilities of the Leu-112 polypeptides suggested that the protein was cleaved incorrectly. This aberrant cleavage appears to have abolished the ability of the F protein to cause syncytium formation. The data indicate that the arginine 112 residue is critical for the correct proteolytic cleavage that is required for the membrane fusion activity of the MV F protein.

Amino Acid Sequence↗
PubMed1994

Functional analysis of N-linked glycosylation mutants of the measles virus fusion protein synthesized by recombinant vaccinia virus vectors.

The role of N-linked glycosylation in the biological activity of the measles virus (MV) fusion (F) protein was analyzed by expressing glycosylation mutants with recombinant vaccinia virus vectors. There are three potential N-linked glycosylation sites located on the F2 subunit polypeptide of MV F, at asparagine residues 29, 61, and 67. Each of the three potential glycosylation sites was mutated separately as well as in combination with the other sites. Expression of mutant proteins in mammalian cells showed that all three sites are used for the addition of N-linked oligosaccharides. Cell surface expression of mutant proteins was reduced by 50% relative to the wild-type level when glycosylation at either Asn-29 or Asn-61 was abolished. Despite the similar levels of cell surface expression, the Asn-29 and Asn-61 mutant proteins had different biological activities. While the Asn-61 mutant was capable of inducing syncytium formation, the Asn-29 mutant protein did not exhibit any significant cell fusion activity. Inactivation of the Asn-67 glycosylation site also reduced cell surface transport of mutant protein but had little effect on its ability to cause cell fusion. However, when the Asn-67 mutation was combined with mutations at either of the other two sites, cleavage-dependent activation, cell surface expression, and cell fusion activity were completely abolished. Our data show that the loss of N-linked oligosaccharides markedly impaired the proteolytic cleavage, stability, and biological activity of the MV F protein. The oligosaccharide side chains in MV F are thus essential for optimum conformation of the extracellular F2 subunit that is presumed to bind cellular membranes.

Animals↗