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Biomedical subjects

G L Brown

Publications and source records attributed to G L Brown.

At least 19 recordsLinked to original sources
PubMed1992

D2 dopamine receptor genotype and cerebrospinal fluid homovanillic acid, 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenylglycol in alcoholics in Finland and the United States.

If a genetic association between the D2 dopamine receptor genotype and alcoholism is mediated by altered dopamine function, then a stronger association might be found in alcoholics who are deviant in indices of dopamine function and by comparing alcoholics to nonalcoholics matched for ethnic origin. Therefore, we evaluated the D2/TaqI polymorphism in 29 impulsive violent alcoholic Finns, 17 nonimpulsive violent alcoholic Finns and 36 Finnish controls free of mental disorders, alcoholism and substance abuse. In 37 of the alcoholics, we measured cerebrospinal fluid (CSF) homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol. There was no relationship between D2/Taq 1 genotype and concentrations of these monoamine metabolites in this group, which exhibits lower CSF HVA and 5-HIAA as compared to controls. There was also no genotypic difference between Finnish alcoholics and nonalcoholic controls. The lack of relationship between D2/Taq1 genotype and HVA concentration was replicated in 24 Caucasian alcoholics in the United States.

Adult↗
PubMed1991

Effect of topical recombinant TGF-beta on healing of partial thickness injuries.

Peptide growth factors produced by platelets, macrophages, epidermal, and dermal cells may play key roles in regulating healing of partial-thickness skin wounds. We examined the effects of recombinant transforming growth factor beta (TGF-beta) on cultures of epidermal and dermal cells in vitro and on healing of partial-thickness injuries in vivo. Increasing concentrations of TGF-beta (0.1, 1, and 10 ng/ml) progressively inhibited serum-stimulated DNA synthesis by up to 95% in cultures of adult human keratinocytes during 48 hr of exposure to TGF-beta. In contrast, TGF-beta (10 and 100 ng/ml) in serum-free media stimulated DNA synthesis by up to 80% compared to serum-free control cultures of adult human dermal fibroblasts. To evaluate the effects of TGF-beta on healing of partial-thickness injuries in vivo, wounds (20 x 20 x 0.6 mm) were created on the dorsal thoracolumbar region of adult pigs by an electrokeratome and were treated daily for 5 days after injury with vehicle or vehicle containing 0.1 or 1 microgram/ml TGF-beta and covered with occlusive dressing. Computerized planimetry of wound photographs demonstrated that TGF-beta treatment stimulated statistically significantly increases in the area of regenerated epidermis compared to wounds treated with saline vehicle on Days 3, 4, 5, and 7 after injury probably due to TGF-beta increasing the rate of epidermal cell migration. In addition, morphometry of biopsy specimens showed that TGF-beta treatment stimulated statistically significant increases in the cross-sectional depths of regenerated dermis compared to wounds treated with saline or Silvadene vehicles on Days 5, 6, and 8 after injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Adenosine receptor-mediated coronary artery relaxation and cyclic nucleotide production.

We investigated the involvement of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) in adenosine (ADO) receptor-mediated coronary artery relaxation. Rings from left anterior descending coronary artery, with the endothelium mechanically removed, contracted with prostaglandin F2 alpha and relaxed in a concentration-dependent manner to ADO, 2-chloroadenosine (CAD), l-N6-(2-phenylisopropyl)adenosine (R-PIA), and 5'-(N-ethylcarboxamido)adenosine (NECA). These relaxations were blocked by addition of the ADO receptor antagonist 8-(sulfophenyl)theophylline (8-SPT), indicating ADO receptor involvement. In an endothelium-free membrane preparation, ADO, CAD, and R-PIA all stimulated adenylate cyclase activity in a concentration-dependent manner, and these responses were blocked by 8-SPT. The increase in adenylate cyclase activity produced by ADO, CAD, and R-PIA was completely dependent on the presence of guanosine 5'-triphosphate, suggesting G protein involvement. Surprisingly, NECA and CGS-21680 did not increase adenylate cyclase activity. Unlike atrial natriuretic factor, neither NECA, CAD, R-PIA, nor ADO increased guanylate cyclase activity, suggesting that cGMP is not involved in ADO receptor-mediated relaxation. Data presented in this study support the hypothesis that ADO receptor-mediated coronary artery relaxation may involve cAMP; however, the inability of NECA and CGS-21680 to stimulate adenylate cyclase suggests that the ADO receptor-signaling mechanisms in coronary artery may be more complicated than agonist interaction with a single adenylate cyclase-coupled A2 adenosine receptor.

Adenosine↗
PubMed1991

Stimulation of healing of chronic wounds by epidermal growth factor.

We evaluated the effect of topical epidermal growth factor treatment on healing of chronic wounds in a prospective, open-label, crossover trial. Five males and four females who ranged in age from 40 to 72 years (average 57 +/- 9 years) were enrolled. Four patients had adult-onset diabetes mellitus, two had rheumatoid arthritis, two had old burn scars, and one had a failed abdominal incision. The average duration of the ulcers prior to treatment with epidermal growth factor was 12 +/- 5 months (range 1 to 48 months). Following failure of the wounds to heal with conventional therapies, including debridement, skin graphs, and vascular reconstruction, wounds were treated twice daily with Silvadene alone for periods ranging from 3 weeks to 6 months. No evidence of healing was observed in any of the patients' wounds during Silvadene treatment, and patients were crossed over to twice a day treatment with Silvadene containing 10 micrograms epidermal growth factor per gram. Wounds of eight patients healed completely with epidermal growth factor-Silvadene treatment in an average of 34 +/- 26 days (mean +/- SD, range 12 to 92 days) and did not reoccur for periods ranging from 1 to 4 years. One patient failed therapy. These results suggest that topical treatment of chronic wounds with epidermal growth factor may stimulate healing.

Administration, Cutaneous↗
PubMed1991

Procurement and transplantation of colonized cadaver skin.

Cadaver skin is an important adjunct to burn care. This study was designed to measure the percentage of its contamination prior to grafting and to determine the clinical safety of its use. Cadaveric homografts from 19 donors were harvested, frozen, thawed, and used as a biological dressing. Cultures were obtained at the time of harvest, after incubation in antibiotics, and at actual transplantation. The homografts were 43 per cent, 68 per cent, and 50 per cent contaminant-free, respectively. Two of 14 patients lost their homografts due to infection. However, no patient developed an infection or lost the homograft due to an organism identified during the pretransplantation processing. Therefore, contaminant-free and slightly contaminated cadaver skin can be used safely as homografts.

Adolescent↗
PubMed1990

Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism.

Using the dopamine D2 receptor clone lambda hD2G1, Blum et al recently found that the D2/Taq I allele (A1) was present in 69% of 35 deceased alcoholics but in only 20% of an equal number of controls. To assess this association further, we evaluated the D2/Taq I polymorphism and a single-strand conformation polymorphism detected by polymerase chain reaction and nondenaturing gel electrophoresis (PCR-SSCP) of the 3' noncoding region of the D2 receptor gene. We studied 40 unrelated white alcoholics, 127 racially matched controls, and two white pedigrees. The Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) clinical diagnostic interviews were rated blindly by two clinicians. The SADS-L interviews and other data were then used to ascertain diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria. Alcoholics were subtyped according to age of onset, severity, presence of antisocial personality, and family history. No significant differences in either D2/Taq I or PCR-SSCP allele frequencies were observed between alcoholics, subpopulations of alcoholics, or controls. The PCR-SSCP polymorphism provided independent information against linkage at the D2 receptor locus. Several recombinants between the D2/Taq I locus and alcoholism were observed in two white families with an alcoholic parent who possessed the A1 allele. This study does not support a widespread or consistent association between the D2 receptor gene and alcoholism.

Adult↗
PubMed1990

Effects of CGS-15943A on the relaxations produced by adenosine analogs in human blood vessels.

The antagonistic effects of CGS-15943A on the relaxations produced by adenosine and its analogs in human blood vessels were investigated in vitro. Donor hearts were the source of coronary arteries, whereas the internal mammary arteries and saphenous veins were obtained from patients undergoing coronary bypass surgery. Adenosine and its analogs, 5'-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CAD), produced concentration-dependent relaxations in KCl-contracted coronary rings. CGS-15943A antagonized, significantly, the relaxations produced by adenosine, NECA and CAD in coronary arteries. Similarly, the adenosine receptor antagonist, 8-phenyltheophylline (8PT, 10-mumol/l), caused a significant attenuation of the relaxing responses to adenosine, NECA and CAD in coronary arteries. In rings obtained from internal mammary arteries and saphenous veins, adenosine, NECA and CAD all produced concentration-dependent relaxations. These relaxations were smaller in magnitude than those obtained in coronary arteries, and were slightly greater in rings contracted with 10 mumol/l prostaglandin F2 alpha (PGF2 alpha) as compared to 35 mmol/l KCl. However, the mammary arteries and saphenous veins relaxed completely in response to 100 mumol/l papaverine. CGS-15943A (10 mumol/l) did not antagonize the relaxing effects of adenosine and its analogs in these vessels. The results show that coronary arteries are more responsive than mammary arteries or saphenous veins to the relaxing effects of adenosine analogs and that these relaxing responses are dependent on the contracting agent. Furthermore, CGS-15943A demonstrated antagonism of the adenosine response in coronary arteries.

Adenosine↗
PubMed1990

Cerebrospinal fluid monoamine metabolites, aggression, and impulsivity in disruptive behavior disorders of children and adolescents.

Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid, a metabolite of serotonin, were measured in relation to aggression, impulsivity, and social functioning in 29 children and adolescents with disruptive behavior disorders. The cerebrospinal fluid 5-hydroxyindoleacetic acid level was low compared with that of age-, sex-, and race-matched patients with obsessive-compulsive disorder. Within the disruptive group, significant negative correlations with age-corrected 5-hydroxyindoleacetic acid level were seen for the child's report of aggression toward people and the expressed emotionality of the child toward his or her mother; other correlations of age-corrected 5-hydroxyindoleacetic acid level with measures of aggression were in the expected negative direction but did not reach statistical significance. Impulsivity per se and socioenvironmental factors were not significantly related to cerebrospinal fluid 5-hydroxyindoleacetic acid concentration.

Adolescent↗
PubMed1990

A segment of Myxococcus xanthus ops DNA functions as an upstream activation site for tps gene transcription.

A segment of DNA located between 131 and 311 base pairs (bp) upstream from the transcriptional start of the Myxococcus xanthus ops gene (-131 to -311) was shown to function as an upstream activation site (UAS) for developmentally regulated transcription from the tps gene promoter region. The activation of early developmental transcription by the ops UAS was independent of orientation and could be increased by the addition of a second copy of the UAS. The ops UAS segment continued to function when placed 1.5 kbp upstream from the transcription initiation site. DNA from the tps promoter region was required for transcriptional activation by the ops UAS, and a specific requirement for the sequence of tps DNA between -34 and -66 was demonstrated. Several specific ops UAS DNA-protein complexes were observed after incubation of this DNA segment with an extract of early developmental M. xanthus cells. Extracts of vegetative cells contained much less ops UAS-specific DNA-binding activity. When the distance between the tps and ops genes was increased from 2 to 15 kbp by insertion of a transduced segment of DNA, the amount of developmentally induced tps RNA was found to be about one-third that found in wild-type M. xanthus. Our observations suggest that the regulatory region of the ops gene functions not only to control ops gene expression but also to increase early developmental expression of the tps gene located about 2 kbp downstream on the M. xanthus chromosome.

Chromosome Mapping↗
PubMed1990

CSF serotonin metabolite (5-HIAA) studies in depression, impulsivity, and violence.

A neuroanatomical central nervous system (CNS) mechanism for the expression of emotions and behaviors in animals has now been proposed for over 50 years. More specifically, alterations in CNS serotonin associated with aggressive behavior in certain animal models have been among the most frequent, reliable, and replicable findings. Because alterations in CNS monoamines, i.e., catechols and indols, have been related to hypotheses for affective disorders and associated with both suicidal and aggressive behaviors, human clinical implications have emerged. The original studies, which reported an association between low cerebrospinal fluid 5-hydroxyindole-acetic acid concentration and impulsive, destructive behaviors, particularly where aggression and violence are involved, have now been replicated rather consistently in a number of countries and cultures.

Aggression↗
PubMed1990

Fluoride produces endothelium-dependent relaxation and endothelium-independent contraction in coronary artery.

NaF produced endothelium-dependent relaxation and endothelium-independent contraction in porcine, bovine, canine and human coronary artery rings precontracted with either KCl or prostaglandin F2 alpha. For practical reasons the porcine coronary artery was selected to investigate the mechanisms responsible for these responses. Methylene blue, indomethacin, N-ethylmaleimide, pertussis toxin and cholera toxin all significantly attenuated the endothelium-dependent relaxation caused by fluoride. Pretreatment with deferoxamine had no effect on relaxation and superoxide dismutase/catalase potentiated the relaxation produced by fluoride. Fluoride also contracted vessels with or without the endothelium to equal tension levels and had no apparent relaxing effect on basal tone. The contraction produced by fluoride was significantly attenuated by pertussis toxin and cholera toxin; however, none of the other agents examined significantly altered contraction. Bradykinin also caused endothelium-dependent relaxation and this response was significantly attenuated by methylene blue but not indomethacin. Therefore, fluoride appears to relax the arteries by releasing an endothelium-derived relaxing factor similar to that released by bradykinin (methylene blue sensitive) and one or more prostanoid type endothelium-derived relaxing factor(s) (indomethacin sensitive). Furthermore, fluoride relaxation and contraction may be guanine nucleotide-binding regulatory protein-mediated based on sensitivity to the guanine nucleotide-binding regulatory protein modulators.

Animals↗
PubMed1990

V-Y advancement flaps. Reusable flaps for pressure ulcer repair.

V-Y advancement modification of skin paddle design for the biceps femoris, tensor fascia lata, transverse lumbar, and gracilis flaps permits readvancement of each of these flaps for recurrent pressure ulcers. Our use of this refinement of these flaps over the past twelve years shows that up to two readvancements of each of these flaps can be done, thus preserving reconstructive options in a patient population prone to pressure ulcer recurrence.

Humans↗
PubMed1979

Plasma levels of d-amphetamine in hyperactive children. Serial behavior and motor responses.

Amphetamine has been clearly documented to be an efficacious treatment for hyperactive children. The pharmacokinetics of amphetamine have been studied in adults, but not in children. Sixteen male children who scored greater than 2SD from norms on Factors I and IV of Conner's Teacher Rating Scale and who were not excluded for reasons to do with medical or psychiatric conditions, intelligence, or age, had a plasma d-amphetamine apparent elimination half-life of 6.8 +/- 0.5h. Peak plasma level occurred between 3 and 4h (62.7 +/- 3.8 and 65.9 +/- 3.6 ng/ml, respectively). Six of these children had a repeat study and there were no significant differences within subject in apparent elimination half-lives and attained peak blood levels. The variation in plasma levels was greater during absorption than during elimination. Both behavioral and motor activity responses as analyzed by differences between amphetamine and placebo days (by paired t-tests) indicate significant responses between hours 1--4; however, these responses do not correlate with plasma amphetamine levels; they occur during the absorption phase. The decreased response to later similar plasma levels of d-amphetamine may be related to depletion of catecholamine stores, to replacement by a 'false neurotransmitter' metabolite of amphetamine, or to alteration in receptor sensitivity.

Child↗
PubMed1979

Alcohol and central serotonin metabolism in man.

Animal studies and some of thephenomena associated with alcoholism in humans suggest that some central effects of alcohol may involve serotonergic systems. The CSF metabolites of serotonin and dopamine, 5-hydroxyindoleacetic acid (5HIAA), and homovanillic acid (HVA) were studied in hospitalized alcoholics. There were no significant differences in HVA levels between groups. The level of 5HIAA of alcoholics in the abstinence phase, 28 to 63 days after their last drink, was significantly lower (21.8 +/- 1.9 ng/mL) than both a nonalcoholic comparison group (31.7 +/- 2.0 ng/mL) and alcoholics in the immediate postintoxication phase, within one to two days after their last drink (32.3 +/- 2.9 ng/mL).

Adult↗
PubMed1979

Aggression in humans correlates with cerebrospinal fluid amine metabolites.

Cerebrospinal fluid of the major central metabolites of serotonin (5HT), norepinephrine (NE), and dopamine (DA)--5-hydroxyindoleacetic acid (5HIAA), 3-methoxy-4-hydroxy=phenylglycol (MHPG), and homovanillic acid (HVA), respectively--were studied in a group of 26 age-similar military men with no history of major psychiatric illness, but with various personality disorders and difficulties adjusting to military life. Independently scored history of aggressive behavior showed a significant negative correlation with 5HIAA (r = -0.78) and a significant positive correlation with MHPG (r = 0.64).

Adult↗
PubMed1979

The role of plasma amine oxidase, platelet monoamine oxidase, and red cell catechol-O-methyl transferase in severe behavioral reactions to disulfiram.

The authors assayed platelet monoamine oxidase (MAO), plasma amine oxidase (AO), and red cell catechol-O-methyl transferase (COMT) in 32 male alcoholics before they began disulfiram treatment. Seven subjects developed psychotic reactions to disulfiram; these 7 had significantly lower pretreatment MAO and AO levels and significantly higher COMT than the patients who had no adverse reactions to disulfiram, which suggests that severe behavioral reactions to disulfiram are associated with differences in enzyme activities.

Adolescent↗