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Biomedical subjects

J R Brown

Publications and source records attributed to J R Brown.

At least 91 records · Page 5Linked to original sources
PubMed1995

The pharmacological modulation of angiogenesis in chronic granulomatous inflammation.

Angiogenesis is required for the progression of chronic inflammation, and agents that alter it can affect the development of inflammation and the consequent tissue destruction. However, in vivo quantification of neovascularization and its modulation by angiostatic and angiogenic agents is difficult. Studies have relied on reported effects of drugs on embryonic and tumor vasculature to infer angiomodulatory actions. We have characterized a vascular casting method that incorporates carmine in gelatin. Vascularity expressed as micrograms dye/mg dry tissue (vascularity index, V.I.) was studied in the murine chronic granulomatous air pouch. Carmine was retained within the vasculature by gelatin, and its content increased before the granulomatous tissue, resulting in a V.I. peak at 5 days, regression and a second peak over 14 to 28 days. The modulation of prostaglandin synthesis, plasma exudation and vasomotor tone showed that the carmine V.I. remained unaffected, unlike Evans blue, illustrating independence from acute inflammatory processes such as vasomotor tone and plasma exudation. The angiogenic stimulus p.o. heparin increased the V.I., whereas a sub-anti-inflammatory dose of cortisone with 1000 U heparin reduced it. Higher doses of heparin overcame this. The potent angiostatic steroid tetrahydrocortisol significantly reduced the V.I. in the absence of heparin. Cortisone exhibited independence from heparin on topical administration in hyaluronan. Dexamethasone inhibited granulomatous tissue development with a resulting increase in V.I. These observations indicated the differential effects of angiostatic and anti-inflammatory steroid activity. The pharmacological modulation of angiogenesis in inflammation can therefore be quantified.

Animals↗
PubMed1995

Nonprescription, padded, lightweight support socks in treatment of mild to moderate lower extremity venous insufficiency.

Currently, strength greater than 20 mm Hg of compression is considered necessary for support hose used to treat symptomatic venous insufficiency in lower extremities. This strength is frequently uncomfortable, which reduces compliance and therefore clinical effectiveness. Whether more comfortable, nonprescription, light-compression support hose is effective in the treatment of mild to moderate venous insufficiency was investigated in 36 men with subjective complaints and objective signs (per Doppler ultrasound) of lower extremity venous insufficiency. All participants wore padded, light-compression (6 mm Hg), crew-height socks for 1 month. Then, participants were assigned to one of two groups on the basis of initial Doppler results. The half with the worst results wore stronger-compression (12 mm Hg) over-the-calf support socks, on the assumption that patients with worse venous insufficiency would require more support; those with the better Doppler results continued to wear the light-compression socks. Participants were retested at monthly intervals for 3 months. In each group, data indicated that the venous insufficiency for all patients improved objectively and subjectively. Many of the objective venous values improved with either statistical or highly statistical significance--specifically deep venous valve function, superficial venous valve functions, and venous capacity--without statistically altering arterial function. Improvement occurred in the first month of the trial and continued throughout the study. The use of light-compression support socks is effective and should be considered as a first line of therapy in treatment of mild to moderate venous insufficiency.

Adult↗
PubMed1995

Variability of day 3 follicle-stimulating hormone levels in eumenorrheic women.

OBJECTIVE: To assess the intercycle variability of early follicular follicle-stimulating hormone (FSH) and estradiol (E2) levels in eumenorrheic women according to age. STUDY DESIGN: Forty-eight female volunteers with regular menstrual cycles were studied. Serum samples were obtained on cycle day 3 in multiple cycles over a one-year period. Serum was also obtained on consecutive cycle days 2, 3 or 4 in a single cycle in 20 participants. All samples were assayed for FSH and E2 by radioimmunoassay. RESULTS: In women under 40 years of age, all initial day 3 FSH levels were < 20 mIU/mL, and 15% of subjects had a subsequently elevated day 3 FSH level (> or = 20 mIU/mL) within the year. In eight women 40-44 years of age, 75% had an initial day 3 FSH level < 20 mIU/mL, but half of them subsequently had an elevated level, > 20 mIU/mL, within the year. Between cycle days 2, 3 and 4, FSH (coefficient of variation [CV] = 14.8%, 95% confidence interval (CI) = 11.4-18.3%) varied less than E2 (CV = 31.1%, 95% CI = 21.5-40.6%). CONCLUSION: A single day 3 FSH level < 20 mIU/mL is highly predictive of all subsequent values within a year and occurred only in women under 40. An FSH level drawn on cycle day 2 or 4 will probably be within 18% of the day 3 value, but the E2 level may vary by up to 40%.

Adult↗
PubMed1995

The modulation of granulomatous tissue and tumour angiogenesis by diclofenac in combination with hyaluronan (HYAL EX-0001).

In a novel application, hyaluronan has been utilized as a delivery system for topical and i.v. therapeutics. Clinical trials and case reports show that topical diclofenac delivered in hyaluronan (HYAL CT-1101) is effective against basal-cell carcinoma and actinic keratosis. The effect of this drug formulation on tumour growth and angiogenesis, as well as granulomatous tissue angiogenesis, has been investigated experimentally. The evidence that hyaluronan has a permissive effect on the inhibition of granulomatous tissue angiogenesis by diclofenac (as assessed by the carminel/gelatin vascular casting method) when injected into the lesion or applied topically is reviewed. Topical diclofenac in hyaluronan also induces a regression of the existing neo-vasculature of granulomatous tissue when applied therapeutically. The diclofenac formulated in hyaluronan was also found to be profoundly effective against the development of subcutaneous Colon-26 tumours in syngeneic balb/c mice (T/C ratio after 12 days topical application of 0.174, p < 0.0001). Analysis of the tumour vasculature showed that vascular development was retarded by 12 days. This was shown by the reduction in the tumour density of carmine in the vascular casts, as well as reduced blood-vessel density visualized by rat anti-mouse CD31 immunohistology. Hyaluronan alone had a significant effect on tumour development with a 50% inhibition of tumour growth and only a transient reduction in vascularity. The effects noted when diclofenac is formulated in hyaluronan, and applied topically, could be related to trans-dermal delivery and deposition properties of hyaluronan, and to the binding properties of hyaluronan to areas of pathology with high expression of hyaluronan receptors such as RHAMM, ICAM-1, and CD44.

Animals↗
PubMed1994

Tempo, mode, the progenote, and the universal root.

Early cellular evolution differed in both mode and tempo from the contemporary process. If modern lineages first began to diverge when the phenotype-genotype coupling was still poorly articulated, then we might be able to learn something about the evolution of that coupling through comparing the molecular biologies of living organisms. The issue is whether the last common ancestor of all life, the cenancestor, was a primitive entity, a progenote, with a more rudimentary genetic information-transfer system. Thinking on this issue is still unsettled. Much depends on the placement of the root of the universal tree and on whether or not lateral transfer renders such rooting meaningless.

Animals↗
PubMed1994

Evolutionary relationships of bacterial and archaeal glutamine synthetase genes.

Glutamine synthetase (GS), an essential enzyme in ammonia assimilation and glutamine biosynthesis, has three distinctive types: GSI, GSII and GSIII. Genes for GSI have been found only in bacteria (eubacteria) and archaea (archaebacteria), while GSII genes only occur in eukaryotes and a few soil-dwelling bacteria. GSIII genes have been found in only a few bacterial species. Recently, it has been suggested that several lateral gene transfers of archaeal GSI genes to bacteria may have occurred. In order to study the evolution of GS, we cloned and sequenced GSI genes from two divergent archaeal species: the extreme thermophile Pyrococcus furiosus and the extreme halophile Haloferax volcanii. Our phylogenetic analysis, which included most available GS sequences, revealed two significant prokaryotic GSI subdivisions: GSI-alpha and GSI-beta. GSI-alpha-genes are found in the thermophilic bacterium, Thermotoga maritima, the low G+C Gram-positive bacteria, and the Euryarchaeota (includes methanogens, halophiles, and some thermophiles). GSI-beta-type genes occur in all other bacteria. GSI-alpha- and GSI-beta-type genes also differ with respect to a specific 25-amino-acid insertion and adenylylation control of GS enzyme activity, both absent in the former but present in the latter. Cyanobacterial genes lack adenylylation regulation of GS and may have secondarily lost it. The GSI gene of Sulfolobus solfataricus, a member of the Crenarchaeota (extreme thermophiles), is exceptional and could not be definitely placed in either subdivision.

Amino Acid Sequence↗
PubMed1993

Substance P selectively activates TNF-alpha gene expression in murine mast cells.

There is increasing evidence that the neurologic system is capable of modulating a wide range of immunologic responses, including certain inflammatory processes in the lung, gastrointestinal tract, and skin. It has been proposed that secreted neuropeptides such as substance P (SP) may mediate these neuroinflammatory interactions by binding to and stimulating immune cells such as mast cells and lymphoid cells. SP is secreted in a variety of tissues by an extensive network of neurosensory C and A5 fibers in response to a wide range of noxious stimuli and injury. Previous studies to examine the effect of SP on mast cells have focused on its role in triggering histamine release and mediating immediate hypersensitivity responses. Recently it was demonstrated that mast cells are also capable of secreting multiple cytokines including TNF-alpha, IL-1, IL-3, IL-4, IL-6, and GM-CSF. In this study we tested the possibility that SP may also influence mast cell-mediated late inflammatory events by modulating the production of one or several of these cytokines. Our results indicate that SP induces TNF-alpha mRNA expression and TNF-alpha secretion in a dose-dependent manner in a murine mast cell line, CFTL12. Likewise, SP stimulates TNF-alpha secretion in freshly isolated murine peritoneal mast cells. The induction of mast cell TNF-alpha is selective, since SP does not stimulate the production of IL-1, IL-3, IL-4, IL-6, or GM-CSF in these cells. The CFTL 12 mast cell line constitutively expresses high levels of SP receptor mRNA which is not modulated by PMA/cycloheximide treatment or SP. These results further support the concept that the neurologic system modulates inflammatory events by neuropeptide-mediated mast cell cytokine release.

Animals↗
PubMed1993

Intraspecific DNA sequence variation of the mitochondrial control region of white sturgeon (Acipenser transmontanus).

Intraspecific sequence variation in the D-loop region of mtDNA in white sturgeon (Acipenser transmontanus), a relict North American fish species, was examined in 27 individuals from populations of the Columbia and Fraser rivers. Thirty-three varied nucleotide positions were present in a 462-nucleotide D-loop sequence, amplified using the polymerase chain reaction. Bootstrapped neighbor-joining and maximum-parsimony trees of sequences from 19 haplotypes suggest that the two populations have recently diverged. This is consistent with the hypothesis that the Columbia River, a Pleistocene refugium habitat, was the source of founders for the Fraser River after the last glacial recession. On the basis of a divergence time of 10-12 thousand years ago, the estimated substitution rate of the white sturgeon D-loop region is 1.1-1.3 x 10(-7) nucleotides/site/year, which is comparable to rates for hypervariable sequences in the human D-loop region. Furthermore, the ratio of mean percent nucleotide differences in the D-loop (2.27%) to that in whole mtDNA (0.54%, as estimated from restriction-enzyme data) is 4.3, which is similar to the fourfold-to-fivefold-higher substitution rate estimated for the human D-loop. The high nucleotide substitution rate of the hypervariable region indicates that the vertebrate D-loop has potential as a genetic marker in molecular population studies.

Animals↗
PubMed1993

Temperature and flow rate effects on mass median diameters of thermally generated malathion and naled fogs.

The effects of temperature and flow rate on mass median diameters (mmds) of thermally generated aerosol clouds were studied. Number 2 fuel oil alone, undiluted and diluted malathion 91, and undiluted naled were examined. There was a significant flow rate x temperature interaction on the mmds of diluted malathion fogs: i.e., differences among flow rates depended on temperature and vice versa.

Aerosols↗
PubMed1993

A cell culture model system for genetic analyses of the cell cycle by targeted homologous recombination.

Analysis of how external proliferation signals impinge on the regulation of the cell cycle is ideally performed in cells that are capable of normal physiological withdrawal into the quiescent (G0) phase of the cell cycle as well as resumption of growth following appropriate stimuli. Targeted homologous recombination (gene targeting) provides an important new approach to determine the function of specific genes in these cellular processes. Current gene targeting methodology necessitates the use of immortal and stably diploid cell lines. This report investigates several rodent cell lines, by both genetic and physiological criteria, for use in gene targeting studies of the G0 to G1 transition. All murine cell lines examined were aneuploid. Some rat cell lines were euploid by chromosome number, but three specific genes, c-myc, c-raf-1 and Rb, were not always diploid. Only one cell line, an early-passage subclone of the Rat-1 cell line, was diploid for c-myc, c-raf-1 and Rb. An hprt- derivative of this cell line was isolated (designated TGR-1) and its karyotype was established by G-banding. TGR-1 cells were shown to withdraw into G0 upon serum starvation and to uniformly enter S phase after refeeding. Expression patterns of the c-myc, c-raf-1 and Rb genes and several properties of the gene products were found to be normal. The frequency of targeted homologous recombination of the c-myc and c-raf-1 loci was found to be within values observed with other cell lines. Thus, by both genetic and physiological criteria the TGR-1 cell line is a good model system for the analysis of the roles of c-myc, c-raf-1 and Rb in signal transduction, and will probably prove useful in studies involving other genes.

Animals↗
PubMed1993

A comparison of Teflon slides and the Army Insecticide Measuring System for sampling aerosol clouds.

The effects of method of droplet analysis, reader of Teflon slides and distance on mass median diameter of a Cythion aerosol cloud were examined in the calibration of an Army Insecticide Measuring System (AIMS). There were no significant differences in results among readers and between the AIMS and readers. There were slight but statistically significant differences between readers of Teflon slides and between the methods of analysis. Data supports the manufacturer's recommendation that, for the AIMS, the distance at which an aerosol generator air blast is between 3 and 7 m3 s-1 must be determined.

Aerosols↗
PubMed1993

Malathion aerosol cloud behavior in a Coastal Plains pine flatwoods.

The study examines malathion aerosol cloud behavior in a North Florida pine flatwoods. Droplet mass median diameters (MMD) decreased over distance in both open and pine flatwoods. A sharp decrease in number of aerosol droplets per cm2 occurred between 3.1 and 15.2 m and a gradual decline in droplets per cm2 occurred beyond 15.2 m in both treatment areas. There were no interactions between habitat and distance in regard to MMD or droplets per cm2. Analysis of variance models accounted for 82% of the variability in the MMD data and 79% of the variability in the number of droplets per cm2.

Aerosols↗
PubMed1992

Mitochondrial DNA length variation and heteroplasmy in populations of white sturgeon (Acipenser transmontanus).

Southern blot analysis was used to quantify the extent of mtDNA D-loop length variation in two populations of white sturgeon, Acipenser transmontanus. Over 42% of individuals were heteroplasmic for up to six different mtDNA length variants attributable to varying copy numbers of an 82-bp repeat sequence. Chi-square analyses revealed that the frequencies of length genotypes and the incidence of heteroplasmy were significantly different between Fraser and Columbia River sturgeon populations but not between restriction site haplotypes. Heteroplasmic fish have, on average, higher copy number than homoplasmic fish. Forty-five of 101 homoplasmic individuals carry only a single copy of the repeat, while none of the 73 heteroplasmic fish has the single repeat as the predominant variant. On the basis of differences in frequency distributions of copy number within and between fish, we suggest that (1) heteroplasmy is maintained by high recurrent mutation of multiple copy genomes, favoring increased copy number and (2) the mutation pressure toward higher copy number heteroplasmy is partially offset by selection to reduced genome size and segregation to the homoplasmic condition.

Animals↗
PubMed1992

Talk with your mother or your sibling? Developmental changes in early family conversations about feelings.

Developmental changes in the pattern of family conversations and talk about feelings were examined in a longitudinal study of 50 families observed at home when the second-born children were 33 and 47 months old. Significant increases were noted in the total amount of talk and the frequency of talk about feelings between sibling pairs as well as decreases in the amount of mother-child conversation and references to feelings. Differences in whose feelings were discussed and in the context of references to feelings were found for mother-child and sibling-child dyads. Developmental changes in the children's use of feeling state language co-occurred with the increase in interaction between children and their siblings. The findings contrast the "complementary" nature of mother-child interaction and the "reciprocal" nature of child-sibling interaction and support the argument that the quality of particular relationships influences the use children make of their communicative competence.

Child Development↗
PubMed1992

Method for analysis, and distribution profile, of covalently-linked ferritin-daunorubicin conjugate in the blood of trypanosome-infected mice.

Daunorubicin is a highly potent trypanocide in-vitro but is inactive in-vivo. When daunorubicin is conjugated to bovine serum albumin or horse spleen ferritin using Schiffs base linkages, the complex is trypanocidal in-vitro and in-vivo. We have developed novel analytical methods, using HPLC with fluorimetric detection, for the quantitation of daunorubicin and doxorubicin in biological samples, either as unconjugated drug, or when covalently linked to macromolecules or particles. Ferritin-daunorubicin conjugate (25 mg kg-1) was administered intraperitoneally to mice infected with monomorphic Trypanosoma brucei rhodesiense; peak plasma levels occurred after 1.5 h, and were 5 times higher than those resulting from administration of an equivalent amount of unconjugated daunorubicin. Plasma levels then declined rapidly (t1/2 for 1-6 h period was 0.58 and 0.86 h respectively for conjugated and unconjugated daunorubicin). However, higher plasma levels were seen 24 h after treatment, suggesting the distribution profile of daunorubicin when conjugated to ferritin is multiphasic with resultant high levels of daunorubicin obtained for a prolonged time period.

Animals↗
PubMed1992

Passive exposure to cocaine in medical personnel and its effect on urine drug screening tests.

This report studies the importance of passive exposure of medical personnel to cocaine hydrochloride and its impact on urine screening testing. Eleven medical staff members were exposed to cocaine hydrochloride by means of aerosol and cutaneous application, similar to that which may occur in medical practice. Urine drug screening tests were negative for everyone tested. This finding is supported by known drug kinetics. It is unlikely that a single passive exposure of medical staff to cocaine hydrochloride will produce a positive urine screening test. In all cases of positive urine tests, contaminants should be tested for which may indicate a source of the drug. The routine use of gloves and masks--which is recommended to prevent HIV infection--should further decrease medical personnel's passive exposure to cocaine hydrochloride.

Administration, Cutaneous↗
PubMed1992

Feeding wash water solids to sows during gestation and lactation: sow productivity, pig performance, and tissue compositions.

Diets containing 0, 10, or 20% dried wash water solids (WWS) from a milk processing plant were fed to 54 Yorkshire gilts (160 to 270 kg) for five parities. Feed intake, weight changes, and morbidity of sows were measured; number of pigs per litter, birth weight, and weight gain of pigs were also determined. Blood, tissue, and milk samples were taken from sows for hematological and mineral analyses, and tissue samples were taken from newborn pigs from each treatment per parity. Overall, initial sow weight, sow weight at weaning, and weight losses were not affected (P greater than .05) by treatment. At 107 d of gestation, overall weights decreased (P less than .05) linearly with level of WWS in the diet. The number of pigs per litter and weight of pigs were not affected (P greater than .10) by diet. Concentrations of NA (P less than .10) and Cd (P less than .05) were lower in kidney of sows fed 20% WWS, and concentrations of Zn were lower in bone and in kidney of sows fed the 20% WWS diet. The Sr and Ba concentrations increased (P less than .05, P less than .10) linearly in bone from sows with level of WWS in the diet. In pigs, concentrations of Mn in kidney and Zn in liver were lower for the 20% WWS treatment. In conclusion, feeding WWS to sows over five parities had minimal adverse effects on sow productivity and pig performance; the reduction in Zn concentrations in tissues of sows and pigs seemed to be related to the Ca content of WWS.

Animal Feed↗