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Biomedical subjects

M Brown

Publications and source records attributed to M Brown.

At least 19 recordsLinked to original sources
PubMed1992

Flavobacterium indologenes infection in leopard frogs.

An investigation of an epidemic of infectious disease in a frog (Rana pipiens) colony was conducted. Six of 40 frogs in a continuous (once through) water flow housing system had weight loss, swollen abdomen, corneal edema, uveitis, subcutaneous edema, petechial hemorrhage, incoordination, and respiratory distress. The frogs had lesions consistent with bacterial septicemia. A gram-negative, nonfermenting bacillus, Flavobacterium indologenes (Flavobacterium sp biovar IIb), was isolated in pure culture from tissues and blood. The clinical isolate was used to inoculate healthy frogs sc. An isolate identical to the one isolated from the sick frogs was recovered from tissues and blood of the inoculated frogs. Inoculation of the housing water in a nonflow-through system did not result in disease, despite proliferation of the Flavobacterium spp in the water; therefore, it is likely that establishment of infection requires the presence of the organism in sufficient numbers and a portal of entry into the body.

Animals↗
PubMed1992

A controlled trial comparing continued zidovudine with didanosine in human immunodeficiency virus infection. The NIAID AIDS Clinical Trials Group.

BACKGROUND: Although zidovudine is effective in patients with human immunodeficiency virus (HIV) infection, its efficacy may decline with prolonged use. Didanosine is another inhibitor of HIV reverse transcriptase. We evaluated the effectiveness of changing anti-HIV treatment from zidovudine to didanosine. METHODS: This multicenter, double-blind study involved 913 patients who had tolerated zidovudine for at least 16 weeks. The patients had the acquired immunodeficiency syndrome (AIDS), AIDS-related complex with less than or equal to 300 CD4 cells per cubic milliliter, or asymptomatic HIV infection with less than or equal to 200 CD4 cells per cubic milliliter. They were randomly assigned to receive 600 mg per day of zidovudine, 750 mg per day of didanosine, or 500 mg per day of didanosine. RESULTS: There were significantly fewer new AIDS-defining events and deaths among the 298 subjects assigned to 500 mg per day of didanosine than among the subjects who continued to receive zidovudine (relative risk, 1.39; 95 percent confidence interval, 1.06 to 1.82; P = 0.015). With 750 mg of didanosine, there was no clear benefit over zidovudine (relative risk, 1.10; 95 percent confidence interval, 0.86 to 1.42). The efficacy of didanosine was unrelated to the duration of previous zidovudine treatment. In the two didanosine groups, there were improvements in the number of CD4 cells (P less than 0.001 for both groups) and in p24 antigen levels (P = 0.03 in the 500-mg group; P = 0.005 in the 750-mg group), as compared with the zidovudine group. CONCLUSIONS: Changing treatment from zidovudine to 500 mg per day of didanosine appears to slow the progression of HIV disease.

AIDS-Related Complex↗
PubMed1992

Eicosatetraynoic and arachidonic acid-induced changes in cell membrane fluidity consonant with differences in computer-aided design-structures.

ETYA (5,8,11,14-eicosatetraynoic acid), a competitive analogue of arachidonic acid (AA), inhibits the proliferation of U937 (human monoblastoid) and PC3 (human prostate) cancer cells, without the overt cytotoxicity associated with AA at similar concentrations. The mechanism of inhibition is not established. ETYA at 100 microM acutely increased whole cell and isolated microsomal membrane fluidity of both cell lines to a greater extent than arachidonic acid. PC3 cells incubated with ETYA for 72 h evidenced increased membrane fluidity. This was measured by the fluorescence polarization parameter, R, using the probes TMA-DPH and DPH for whole cell and isolated membrane fractions, respectively. Compared with whole cells, isolated membranes yielded a 10-20-fold increase in fluorescence intensity. The intramolecular conformational profiles of both ETYA and AA were explored using a combination of molecular mechanics energy minimization and molecular dynamics simulation. While it is possible that not all of the low energy conformational states of either molecule were sampled, the large number of low-energy conformers determined for ETYA correspond to kink deformed conformers relative to the family of AA conformers. These kinks make the molecular cross sections of ETYA larger than AA and arise from the four alkyne bond geometries. This structural finding is consistent with ETYA's greater effect on membrane fluidity. Dissociation between the extent of change in membrane fluidity due to ETYA or AA and inhibition of DNA synthesis can suggest that either (A) increased fluidity and inhibition of DNA synthesis are independent, or as we believe more likely, (B) greater membrane fluidity evoked by ETYA is important for inhibiting DNA synthesis, while changes induced by AA are insufficient or differ qualitatively from those required to initiate and sustain these nonlethal events.

Arachidonic Acids↗
PubMed1992

Effects of ageing and exercise on soleus and extensor digitorum longus muscles of female rats.

The effects of ageing and of exercise on muscle mass, fiber cross-sectional area, and fiber type composition of a weight-bearing muscle, the soleus and a non-weight-bearing muscle, the extensor digitorum longus (EDL) were investigated in female Long-Evans rats. The animals were exercised by means of voluntary wheel running beginning at 4 months. Runners and sedentary controls were studied at 9 months and 27 months of age. In sedentary rats, the soleus muscle weighed 26% less, and the EDL weighed 19% less at age 27 months, than at 9 months. This decline in muscle mass was accounted for by a similar decrease in muscle fiber cross-sectional area. The wheel running resulted in significant hypertrophy of the soleus in both 9- and 27-month-old rats; as a consequence the 27-month-old runners had larger soleus muscles than the 9-month-old sedentary rats. The running did not prevent atrophy of the EDL in the old rats, but did increase the proportion of type IIa fibers. The exercise also increased the number of capillaries per fiber in the soleus muscles of both young and old rats. In conclusion, the finding that wheel running prevented atrophy with ageing of the weight-bearing soleus but not of the non-weight-bearing EDL emphasizes the specificity of exercise, and shows that exercise-induced muscle hypertrophy can be maintained in old age by appropriate exercise.

Aging↗
PubMed1992

Immunologic memory to phosphocholine keyhole limpet hemocyanin. Recurrent mutations in the lambda 1 light chain increase affinity for antigen.

Anti-phosphocholine (PC)-keyhole limpet hemacyanin hybridomas representative of a memory response that express the lambda 1 L chain isotype have a high reactivity to PC-protein. A common feature of these hybridomas possessing high affinity for PC-protein is the occurrence of somatic mutations resulting in replacement changes in three CDR2 positions of the lambda 1 L chain. The influence of each of these three positions on the Ag binding properties of these antibodies was examined by site-specific mutagenesis and expression of recombinant antibody molecules by transfected cells. Affinity measurements and fine specificity profile determinations demonstrated the importance of the three lambda 1 CDR2 positions in Ag binding. Compared to antibodies expressing germline lambda 1, including one with an additional junctional serine that is not encoded by V or J, those antibodies possessing critical changes in CDR2 would have a strong selective advantage based on affinity differences for Ag. Sequence analysis of a group of clonally related hybridomas expressing mutated lambda 1 genes allowed construction of a hypothetical genealogic tree that suggests selection based on changes in CDR2 of lambda 1 in the absence of H chain mutations. The results are consistent with stepwise acquisition of mutations and selection based on affinity constraints.

Animals↗
PubMed1992

Initial experience with a new compression device for hemostasis after femoral arterial puncture.

We evaluated a new hemostasis device to maintain focused pressure over the femoral artery puncture site for 2-6 hours in 330 cases after diagnostic catheterization or coronary angioplasty. No patient developed later hematoma or vascular complications. The initial favorable experience suggests that this hemostasis device has advantageous features of stability and site visualization and is a suitable adjunct to current methods of maintaining puncture site pressure after brief manual compression following arterial catheterization.

Cardiac Catheterization↗
PubMed1992

Interaction of amyloid beta protein (25-35) with tachykinin receptors.

Amyloid beta protein (25-35) failed to significantly interact with tachykinin NK1 (rat forebrain, guinea-pig ileum) NK2 (rabbit pulmonary artery, hamster trachea) or NK-3 (guinea-pig cortex) receptors, as determined by radioligand binding and functional assays. A weak interaction (Ki 14.8 microM) was detected with NK2 receptors in rat small intestine. It appears unlikely that direct interaction with tachykinin receptors may account for the reported ability of amyloid beta protein (25-35) to affect neuronal survival.

Amino Acid Sequence↗
PubMed1992

A new cause of trigger thumb.

We report a case of severe painful triggering in the thumb caused by intermittent locking of the interphalangeal joint by a sesamoid bone. The triggering was corrected by excision of the interphalangeal joint sesamoid bone.

Adolescent↗
PubMed1992

Cochleotopic selectivity of a multichannel scala tympani electrode array using the 2-deoxyglucose technique.

The 2-deoxyglucose (2-DG) technique was used to study the cochleotopic selectivity of a multichannel scala tympani electrode array in four cats with another acting as an unstimulated control. Each animal was unilaterally deafened and a multichannel electrode array inserted 6 mm into the scala tympani. Thresholds to electrical stimulation were determined by recording electrically evoked auditory brainstem responses (EABRs). Each animal was injected with 2-DG, and electrically stimulated using bipolar electrodes located either distal or proximal to the round window. The contralateral ear was stimulated with acoustic tone pips at frequencies that matched the electrode place. Stimulation of both distal and proximal bipolar electrodes at 3 x EABR threshold, evoked localized 2-DG labelling in both ipsilateral cochlear nucleus (CN) and the contralateral inferior colliculus (IC), which was very similar in orientation and breadth to labelling evoked by the contralateral tone pips. The cochleotopic position of labelling to proximal stimulation was located in the 24-26 kHz region of each structure, whereas the distal labelling was located around 12 kHz. Distal stimulation at 10 x EABR threshold produced very broad 2-DG labelling in IC centered around the 12 kHz place. The present 2-DG results clearly illustrate cochleotopic selectivity using multichannel bipolar scala tympani electrodes. The extent of this selectivity is dependent on electrical stimulus levels. The 2-DG technique has great potential in evaluating the efficacy of new electrode array designs.

Acoustic Stimulation↗
PubMed1992

Prevention of hyperbaric-associated middle ear barotrauma.

STUDY OBJECTIVE: To determine the efficacy of topical nasal decongestant in the prevention of middle ear barotrauma in patients undergoing hyperbaric oxygen therapy. DESIGN: Prospective, parallel, double-blind, randomized trial. SETTING: University-affiliated community hospital emergency department with hyperbaric oxygen facilities. PARTICIPANTS: Sixty patients undergoing hyperbaric oxygen therapy; 30 subjects in each treatment arm. INTERVENTIONS: After randomization, consenting patients were given two sprays of oxymetazoline hydrochloride or sterile water, 15 minutes before hyperbaric oxygen therapy. Collected data included patient demographics, ear examinations before and after hyperbaric oxygen treatment, and subjective ear complaints. The otoscopic appearance of the tympanic membrane was graded according to the amount of hemorrhage in the eardrum, with Teed scores ranging from 0 (symptoms only) to 5 (gross hemorrhage and rupture). RESULTS: The treatment groups were similar with regard to age, sex, and medical history. Ear discomfort during hyperbaric oxygen therapy was present in 63% (19 of 30) of those receiving oxymetazoline versus 67% (20 of 30) of the control group (P = .99). Likewise, both groups had similar Teed scores after hyperbaric oxygen therapy (P = .88). No adverse effects were noted. CONCLUSION: The results of this pilot study suggest that topical decongestants may not be effective in preventing middle ear barotrauma during hyperbaric oxygen therapy.

Administration, Topical↗
PubMed1992

Pseudoephedrine for the prevention of barotitis media: a controlled clinical trial in underwater divers.

STUDY OBJECTIVE: To determine the efficacy and safety of decongestant prophylaxis among first-time underwater divers in the prevention of barotitis media (middle ear squeeze). DESIGN: Randomized, double-blind, prospective clinical trial. SETTING: Recreational diving schools in Panama City, Florida. TYPE OF PARTICIPANTS: One hundred twenty volunteer scuba divers under the supervision of certified instructors. INTERVENTIONS: After randomization, each subject received a 60-mg tablet of pseudoephedrine or placebo 30 minutes before diving. Prospective data were collected, including subject demographics, signs and symptoms of middle ear squeeze during the dive, and possible drug side effects. The otoscopic appearance of the tympanic membrane was graded according to the amount of hemorrhage in the eardrum, with Teed scores ranging from 0 (normal) to 5 (gross hemorrhage and rupture). chi 2 and t-tests were applied with significance set at P less than .05). The Mantel-Haenszel test was used to test the null hypothesis that the mean Teed scores of the two treatment groups were equal. RESULTS: A total of 116 subjects met the inclusion criteria and completed the study; 60 received 60 mg pseudoephedrine, and 56 received placebo. The treatment groups were similar with regard to age, sex, medical history, and depth of the first dive (P greater than .5). Ear discomfort and blockage during the dive were present in 8% (five of 60) of those receiving pseudoephedrine versus 32% (18 of 56) of the control group (P = .001). Similarly, the pseudoephedrine group had smaller Teed scores after diving than did the control subjects (P = .003). Adverse effects were minimal; two patients experienced dizziness and nausea. CONCLUSION: These results suggest that the use of an oral decongestant before diving decreases the incidence and severity of middle ear squeeze in novice divers.

Adult↗
PubMed1992

Fibrous histiocytoma of the parotid gland.

The light microscopic, electron microscopic, and immunocytochemical characteristics of a case of a fibrous histiocytoma arising in the parotid gland is presented. This neoplasm is very rare in this site and must be distinguished from other spindle cell tumors of the parotid gland, particularly those of epithelial and myoepithelial origins. Histologic characteristics similar to those displayed by dermatofibromas and dermatofibrosarcoma protuberans help to differentiate this tumor from other spindle cell tumors. The absence of cytochemical epithelial markers and the electron microscopic demonstration of fibroblasts and histiocytes are useful in establishing the diagnosis. This tumor, which was confined completely to the parotid gland, appears to have arisen from mesenchymal elements within the gland.

Histiocytoma, Benign Fibrous↗
PubMed1992

Histochemical and enzymatic comparison of the gastrocnemius muscle of young and elderly men and women.

To examine the effects of aging on human skeletal muscle, 10 men and 10 women, 64 +/- 1 yr old (Mean +/- SE), and 10 men and 10 women, 24 +/- 1 yr old, were studied. All subjects were sedentary nonsmokers who were carefully screened for latent cardiovascular, metabolic, or musculoskeletal disease. Needle biopsy samples were obtained from the lateral gastrocnemius muscle and examined using histochemical and biochemical techniques. The percentage of Type I, Type IIa, and Type IIb fibers did not differ with age. However, Type I fibers occupied a larger percent of total muscle area in the older men and women (60.6 +/- 2.6 vs 53.6 +/- 2.0%; p less than .05), because Type IIa and Type IIb fibers were 13-31% smaller (p less than .001) in these subjects. Muscle capillarization and mitochondrial enzyme (i.e., succinate dehydrogenase, citrate synthase, and beta-hydroxyacyl-CoA dehydrogenase) activities were also approximately 25% lower (p less than .001-.05) in the old subjects. Although it is difficult to determine whether these differences are due to aging itself or are simply due to inactivity, these structural and biochemical changes probably contribute to the decreases in muscle mass, strength, and endurance often observed in healthy but sedentary older men and women.

Adult↗
PubMed1992

Antiglobulin testing for CR1-related (Knops/McCoy/Swain-Langley/York) blood group antigens: negative and weak reactions are caused by variable expression of CR1.

The Knops, McCoy, Swain-Langley and York antigens have recently been identified as being on complement receptor type 1 (CR1, CD35, C3b/C4b receptor). We examined the relationship between CR1 expression and the reactivity of the CR1-related blood group antigens with their specific antibodies. RBC from donors of selected phenotypes were tested by hemagglutination using two monoclonal antibodies to CR1, as well as anti-Kna, -McCa, -S1a, -'Kn/McC' and -Yka. Monoclonal antibodies 3D9 and E11 required approximately 250 and approximately 400 CR1/RBC to obtain a positive reaction. Agglutination of antigen-positive cells by human polyclonal antisera was related to the CR1/RBC: thus, cells expressing 20-100 CR1/RBC were negative and included the previously designated null phenotypes for this collection, 100-150 were weak or negative, and greater than 200 were usually positive. One RBC sample carried Yka on the 190,000 dalton (A or F allele), but not the 220,000 dalton (B or S allele) variant of CR1, and gave inconsistent reactions with Yka antisera. These data provide an explanation for certain of the serologic characteristics of the CR1-related blood group antigen system.

Alleles↗
PubMed1992

A block in release of progeny virus and a high particle-to-infectious unit ratio contribute to poor growth of enteric adenovirus types 40 and 41 in cell culture.

The fastidious enteric adenovirus (FEAd) types 40 (Ad40) and 41 (Ad41) are found in stool specimens of infants and young children in association with gastroenteritis. Although they can be isolated routinely from clinical specimens by using 293 cells, they are propagated with variable success in cell lines which support the replication of other adenovirus serotypes. HeLa cells are generally considered to be nonpermissive for the replication of FEAds, but in this study, Ad40 and Ad41 grew to comparable titers in individual 293 and HeLa cells. However, virus was not efficiently released from infected HeLa cells and thus did not undergo multiple cycles of infection in HeLa cell cultures. The block in virus release was not overcome in KB18 cells which, like 293 cells, constitutively express proteins encoded by the E1B region of a subgroup C adenovirus (in this case Ad2). Moreover, it was apparent from these studies that Ad40 and Ad41 have particle-to-infectious unit ratios several orders of magnitude greater than that for Ad5, even in 293 cells which express the E1A and E1B proteins of Ad5 and are considered to be permissive for replication of the FEAds. Neither the block in release of progeny virus nor the high particle-to-infectious unit ratio is explained solely by the defect in expression of the E1B 55K protein identified by Mautner et al. (V. Mautner, N. MacKay, and V. Steinthorsdottir, Virology 171:619-622, 1989; V. Mautner, N. MacKay, and K. Morris, Virology 179:129-138, 1990).

Adenovirus Early Proteins↗
PubMed1992

Dose-response characteristics of human proinsulin and insulin in non-insulin-dependent diabetic humans.

We compared the actions of human proinsulin and insulin on glucose turnover and on intermediary carbohydrate and lipid metabolism in non-insulin-dependent diabetes mellitus (NIDDM). Six diet-controlled weight-matched (25.4 +/- 1.0 kg/m2) NIDDM subjects underwent six separate isoglycemic clamps. Glucose turnover was measured using a primed continuous infusion of [6',6'-2H2]glucose. Each subject received three low-dose intravenous infusions of both insulin and proinsulin. Blood glucose was maintained at 6.7 +/- 0.3 mM during proinsulin and insulin infusion. Insulin (I) infusions gave steady-state levels of 0.12 +/- 0.001 (I1), 0.18 +/- 0.01 (I2), and 0.33 +/- 0.01 nM (I3). Steady-state proinsulin (P) levels were 2.5 +/- 0.1 (P1), 4.3 +/- 0.2 (P2), and 8.8 +/- 0.9 nM (P3). Hepatic glucose production was suppressed equally by proinsulin and insulin at all doses. The metabolic clearance rate of glucose was significantly increased during the insulin infusion compared with proinsulin. The use of [6',6'-2H2]glucose resulted in a mean underestimation of the glucose infusion rate of 10.0 +/- 4.0 and 6.0 +/- 2.5% during the two highest insulin and proinsulin doses, respectively. Proinsulin had a significantly weaker effect than insulin, at the lowest infusion dose, in percent suppression of plasma nonesterified fatty acids, blood glycerol, and beta-hydroxybutyrate levels (all P less than 0.05). Blood lactate levels were lower during the P1 (628 +/- 43 microM) and P2 (657 +/- 93 microM) infusions compared with I1 (776 +/- 60 microM) and I2 (878 +/- 44 microM; P less than 0.05, P less than 0.02), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 2↗
PubMed1992

Skeletal muscle adaptations to endurance training in 60- to 70-yr-old men and women.

Previous studies of endurance exercise training in older men and women generally have found only minimal skeletal muscle adaptations to training. To evaluate the possibility that this may have been due to an inadequate training stimulus, we studied 23 healthy older (64 +/- 3 yr) men and women before and after they had trained by walking/jogging at 80% of maximal heart rate for 45 min/day 4 days/wk for 9-12 mo. This training program resulted in a 23% increase in maximal O2 consumption. Needle biopsy samples of the lateral gastrocnemius muscle were obtained before and after training and analyzed for selected histochemical and enzymatic characteristics. The percentage of type I muscle fibers did not change with training. The percentage of type IIb fibers, however, decreased from 19.1 +/- 9.1 to 15.1 +/- 8.1% (P less than 0.001), whereas the percentage of type IIa fibers increased from 22.1 +/- 7.7 to 29.6 +/- 9.1% (P less than 0.05). Training also induced increases in the cross-sectional area of both type I (12%; P less than 0.001) and type IIa fibers (10%; P less than 0.05). Capillary density increased from 257 +/- 43 capillaries/mm2 before training to 310 +/- 48 capillaries/mm2 after training (P less than 0.001) because of increases in the capillary-to-fiber ratio and in the number of capillaries in contact with each fiber. Lactate dehydrogenase activity decreased by 21% (P less than 0.001), whereas the activities of the mitochondrial enzymes succinate dehydrogenase, citrate synthase, and beta-hydroxyacyl-CoA dehydrogenase increased by 24-55% in response to training (P less than 0.001-0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗