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Biomedical subjects

R L Brown

Publications and source records attributed to R L Brown.

At least 37 records · Page 2Linked to original sources

Analysis of acoustic communication by ants.

An analysis is presented of acoustic communication by ants, based on near-field theory and on data obtained from the black imported fire ant Solenopsis richteri and other sources. Generally ant stridulatory sounds are barely audible, but they occur continuously in ant colonies. Because ants appear unresponsive to airborne sound, myrmecologists have concluded that stridulatory signals are transmitted through the substrate. However, transmission through the substrate is unlikely, for reasons given in the paper. Apparently ants communicate mainly through the air, and the acoustic receptors are hairlike sensilla on the antennae that respond to particle sound velocity. This may seem inconsistent with the fact that ants are unresponsive to airborne sound (on a scale of meters), but the inconsistency can be resolved if acoustic communication occurs within the near field, on a scale of about 100 mm. In the near field, the particle sound velocity is significantly enhanced and has a steep gradient. These features can be used to exclude extraneous sound, and to determine the direction and distance of a near-field source. Additionally, we observed that the tracheal air sacs of S. richteri can expand within the gaster, possibly amplifying the radiation of stridulatory sound.

Animal Communication↗

Improving prevention systems in primary care practices: the Health Education and Research Trial (HEART)

BACKGROUND: The Health Education and Research Trial (HEART) was a multicenter clinical trial designed to test methods to improve primary care practice systems for heart disease prevention services. We present the trial methodology, the practices' use of medical record tools, and changes in documentation of cardiovascular risk factor screening and management. METHODS: Primary care practices were recruited from 4 Midwestern states. The factorial design resulted in 4 study groups: conference only, conference and quality improvement consultations, conference and prevention coordinator, and all interventions combined. Medical record audits and physician, staff, and patient surveys assessed practice change in cardiovascular disease risk factor documentation. RESULTS: Practices participated fully in this project, set goals to improve preventive services, and implemented recommended medical record tools. The number of goals set and the increase in the use of medical record tools were greatest in the combined intervention group, with improvements noted in all groups. The use of patient history questionnaires, problem lists, and flow sheets was significantly higher in the combined intervention group when compared with the conference-only group. Documentation of risk factor screening in a recommended-medical record location improved in all intervention groups, with significant sustained improvements in the practices that received the combined intervention. Documented risk factor management significantly improved in all intervention groups compared with the conference-only control. CONCLUSION: Primary care practices are interested in improving prevention systems and can change these systems in response to supportive external interventions. Promoting organizational change to produce sustained improvement in preventive service clinical outcomes is a complex process that requires further research.

Adult↗

Remission of alcohol disorders in primary care patients. Does diagnosis matter?

BACKGROUND: Alcohol use disorders (AUDs) are prevalent in primary care patient populations. Many primary care patients with AUDs can remit without formal treatment. An understanding of the factors that predispose patients to remission may help primary care physicians provide effective brief counseling for those with mild to moderate disorders and more effectively recommend formal treatment for others. METHODS: A total of 119 eligible and randomly selected primary care patients with alcohol abuse or dependence in remission (as defined in Diagnostic and Statistical Manual of Mental Disorders, third edition, revised) participated in a semistructured telephone interview. RESULTS: Of the subjects, 59.7% were women; 50.4% had been alcohol dependent; 66.3% made a conscious decision to modify their drinking; and 62.1%, including 54.2% of the alcohol-dependent subjects, moderated their drinking without abstaining. Family, emotional, and medical issues most often prompted reduced drinking. Nearly one third of the subjects found specific strategies and rules helpful in reducing their drinking, and many cited circumstances that helped or hindered their efforts. Only 10.9% had formal alcohol treatment. CONCLUSIONS: A significant proportion of patients with AUDs remitted without formal treatment. Abstinence may not be necessary for a subset of dependent patients. When counseling patients with active AUDs, primary care clinicians are advised to counsel patients about the psychosocial and medical reasons to control drinking, promote rule-setting about drinking, help patients avoid circumstances that trigger drinking, and support patients' attempts at moderating drinking rather than abstaining. Motivational interviewing (motivational enhancement therapy) may provide a useful framework for such counseling.

Adolescent↗

Geomicrobiology of subglacial ice above Lake Vostok, Antarctica.

Data from ice 3590 meters below Vostok Station indicate that the ice was accreted from liquid water associated with Lake Vostok. Microbes were observed at concentrations ranging from 2.8 x 10(3) to 3.6 x 10(4) cells per milliliter; no biological incorporation of selected organic substrates or bicarbonate was detected. Bacterial 16S ribosomal DNA genes revealed low diversity in the gene population. The phylotypes were closely related to extant members of the alpha- and beta-Proteobacteria and the Actinomycetes. Extrapolation of the data from accretion ice to Lake Vostok implies that Lake Vostok may support a microbial population, despite more than 10(6) years of isolation from the atmosphere.

Antarctic Regions↗

The single-channel dose-response relation is consistently steep for rod cyclic nucleotide-gated channels: implications for the interpretation of macroscopic dose-response relations.

Cyclic nucleotide-gated channels contain four subunits, each with a C-terminal binding site for cGMP or cAMP. The dose-response relation for activation is usually fit with the Hill equation, I/I(max) = [cGMP]n/([cGMP]n + K(1/2)n, where I/I(max) is the fraction of maximal current, K(1/2) is the concentration of cGMP that gives a half-maximal current, and n is the Hill coefficient, taken as the minimum number of ligands required for significant activation. The dose-response relations in multichannel patches are often fit with Hill coefficients of </=2.0, even though other lines of evidence indicate that these channels contain four binding sites and that the binding of three or four ligands is required for significant opening. We have measured dose-response relations for a large number of single cyclic nucleotide-gated channels composed of the bovine rod alpha subunit. We find that the single-channel Hill coefficient is consistently higher than 2.5, with an average of 3.0 +/- 0.37 over 16 patches. In both multichannel and single-channel patches, large variations in K(1/2) have been observed, and are thought to arise from modifications such as phosphorylation. Here we show that mixtures of single channels with high Hill coefficients and variable K(1/2) values will give rise to shallow macroscopic dose-response relations with anomalously low Hill coefficients. This is because activation occurs over a broad range of cGMP concentrations. Thus, dose-response relations from multichannel patches should be interpreted with caution, particularly when detailed mechanistic issues such as cooperativity are being investigated.

Animals↗

Synthesis, evaluation, and comparative molecular field analysis of 1-phenyl-3-amino-1,2,3,4-tetrahydronaphthalenes as ligands for histamine H(1) receptors.

A series of 1-phenyl-3-amino-1,2,3,4-tetrahydronaphthalenes (1-phenyl-3-aminotetralins, PATs) previously was found to modulate tyrosine hydroxylase activity and dopamine synthesis in rodent forebrain through interaction with a binding site labeled by [(3)H]-(-)-(1R,3S)-trans-H(2)-PAT. Recently, we have discovered that PATs also bind with high affinity to the [(3)H]mepyramine-labeled H(1) receptor in rat and guinea pig brain. Here, we report the synthesis and biological evaluation of additional PAT analogues in order to identify differences in binding at these two sites. Further molecular modifications involve the pendant phenyl ring as well as quaternary amine compounds. Comparison of about 38 PAT analogues, 10 structurally diverse H(1) ligands, and several other CNS-active compounds revealed no significant differences in affinity at [(3)H]-(-)-trans-H(2)-PAT sites versus [(3)H]mepyramine-labeled H(1) receptors. These results, together with previous autoradiographic brain receptor-mapping studies that indicate similar distribution of [(3)H]-(-)-trans-H(2)-PAT sites and [(3)H]mepyramine-labeled H(1) receptors, suggest that both radioligands label the same histamine H(1) receptors in rodent brain. We also report a revision of our previous comparative molecular field analysis (CoMFA) study of the PAT ligands that yields a highly predictive model for 66 compounds with a cross-validated R(2) (q(2)) value of 0.67. This model will be useful for the prediction of high-affinity ligands at radiolabeled H(1) receptors in mammalian brain.

Animals↗

Putative sigma(3) sites in mammalian brain have histamine H(1) receptor properties: evidence from ligand binding and distribution studies with the novel H(1) radioligand [(3)H]-(-)-trans-1-phenyl-3-aminotetralin.

A novel phenylaminotetralin (PAT) radioligand, [(3)H]-(1R, 3S)-(-)-trans-1-phenyl-3-dimethylamino-1,2,3,4-tetrahydronaphthalene ([(3)H]-[-]-trans-H(2)-PAT), is shown here to label a saturable (B(max)=39+/-6 fmol/mg protein) population of sites with high affinity (K(d)=0.13+/-0.03 nM) in guinea pig brain. Consistent with previous studies which showed that PATs stimulate catecholamine (dopamine) synthesis in rat striatum, autoradiographic brain receptor mapping studies here indicate that [(3)H]-(-)-trans-H(2)-PAT-labeled sites are highly localized in catecholaminergic nerve terminal fields in hippocampus, nucleus accumbens, and striatum in guinea pig brain. Competition binding studies with a broad range of CNS receptor-active ligands and CNS radioreceptor screening assays indicate that the pharmacological binding profile of brain [(3)H]-(-)-trans-H(2)-PAT sites closely resembles histamine H(1)-type receptors. Comparative studies using the histamine H(1) antagonist radioligand, [(3)H]mepyramine, indicate that the H(1) ligand binding profile and guinea pig brain distribution of H(1) receptors and [(3)H]-(-)-trans-H(2)-PAT sites are nearly identical; moreover, both sites have about 40-fold stereoselective affinity for (-)- over (+)-trans-H(2)-PAT. These results are discussed in light of previous studies which suggested that PATs stimulate dopamine synthesis through interaction with a novel sigma-type (sigma(3)) receptor in rodent brain; it now appears instead that PATs represent a new class of ligands for brain histamine H(1) receptors that can be stereoselectively labeled with [(3)H]-(-)-trans-H(2)-PAT.

Animals↗

Pseudechetoxin: a peptide blocker of cyclic nucleotide-gated ion channels.

Ion channels activated by the binding of cyclic nucleotides first were discovered in retinal rods where they generate the cell's response to light. In other systems, however, it has been difficult to unambiguously determine whether cyclic nucleotide-dependent processes are mediated by protein kinases, their classical effector enzymes, or cyclic nucleotide-gated (CNG) ion channels. Part of this difficulty has been caused by the lack of specific pharmacological tools. Here we report the purification from the venom of the Australian King Brown snake of a peptide toxin that inhibits current through CNG channels. This toxin, which we have named Pseudechetoxin (PsTx), was purified by cation exchange and RP-HPLC and has a molecular mass of about 24 kDa. When applied to the extracellular face of membrane patches containing the alpha-subunit of the rat olfactory CNG channel, PsTx blocked the cGMP-dependent current with a Ki of 5 nM. Block was independent of voltage and required only a single molecule of toxin. PsTx also blocked CNG channels containing the bovine rod alpha-subunit with high affinity (100 nM), but it was less effective on the heteromeric version of the rod channel (Ki approximately 3 microM). We have obtained N-terminal and partial internal sequence data and the amino acid composition of PsTx. These data indicate that PsTx is a basic protein that exhibits some homology with helothermine, a toxin isolated from the venom of the Mexican beaded lizard. PsTx promises to be a valuable pharmacological tool for studies on the structure and physiology of CNG channels.

Amino Acids↗

Does early ultrasonography affect management of pediatric appendicitis? A prospective analysis.

BACKGROUND: Appendicitis remains a difficult diagnosis in children. Ultrasonography is increasingly used for the diagnosis of appendicitis, although the proper clinical role for this test remains unclear. METHODS: To evaluate the clinical utility of ultrasonography in appendicitis, the authors analyzed prospectively all children evaluated for possible appendicitis from January 1 through December 31, 1997. Children with a high clinical suspicion of appendicitis were referred for surgery (n = 122). Children with equivocal findings of appendicitis were referred for early ultrasonography (EUS) and formed the study cohort (n = 103). An initial management plan was made to operate or observe each patient, and a risk of appendicitis (doubtful, possible, probable) was assigned by a pediatric surgery fellow. EUS was then performed, and its effect on management was assessed. RESULTS: Using clinical judgment to operate at initial presentation, the sensitivity was 38% and specificity was 95%. Using EUS alone, the sensitivity was 87% and specificity was 88%. The management of 30 of 103 patients (30%) was changed after EUS, including a decision to operate in 28 patients and a decision not to operate in two patients. CONCLUSIONS: EUS appears to have substantial clinical utility in children with equivocal findings of appendicitis, and its use complements the clinical management. The use of EUS can improve patient care and reduce hospital resource utilization.

Adolescent↗

Observation of splenic trauma: when is a little too much?

A 12-year-old boy was treated conservatively for a grade II splenic laceration. On discharge, he was instructed to avoid contact sports, running, and strenuous physical activity. Thirty-eight days later, after diving off the side of a swimming pool, he had abdominal pain, nausea, and diaphoresis. On admission, he was hemodynamically unstable. Results of a diagnostic lavage showed gross blood. At laparotomy, a fractured spleen was found, and splenectomy was performed. He recovered without complication. This case questions the activity restrictions placed on patients with conservatively managed splenic trauma. Avoidance of only contact sports and heavy exertion may be inadequate.

Child↗

Gastrointestinal bleeding in infants and children: Meckel's diverticulum and intestinal duplication.

Gastrointestinal bleeding in infants and children can be quite alarming and anxiety-provoking for parents and caregivers alike. In most cases the cause is benign, and the course self-limited. However, in the patient with significant bleeding, an aggressive diagnostic approach is warranted. The differential diagnosis can be extensive and varies depending on the age of the patient. Meckel's diverticula and intestinal duplications may cause gastrointestinal bleeding in almost any age group and require a high index of suspicion for diagnosis. Bleeding usually is painless but may be massive. The advent of technetium (Tc) 99m pertechnetate radionuclide scanning has greatly facilitated the diagnosis of Meckel's diverticula and may also be useful for intestinal duplications. A positive scan requires the presence of ectopic gastric mucosa, which may be identified in both Meckel's diverticula and intestinal duplications. The significance of ectopic gastric mucosa is that it contains acid-secreting parietal cells, which may cause ulceration and bleeding. Only rarely are intestinal duplications diagnosed preoperatively. After initial fluid resuscitation, bleeding from Meckel's diverticula and intestinal duplications require surgical intervention. Resection is the treatment of choice. Diverticulectomy or segmental bowel resection including the diverticulum should be performed for bleeding Meckel's diverticula. It is important to remove the ectopic mucosa and site of ulceration to prevent rebleeding episodes. Intestinal duplications share a common wall and blood supply with native bowel. Segmental resection is indicated if it can be performed without sacrificing a significant portion of bowel. A recent advance has been laparoscopic-assisted resection of Meckel's diverticula and intestinal duplication cysts. With the aid of the laparoscope, extracorporeal or intracorporeal resection may be performed.

Child↗

Inhibition of plant-pathogenic fungi by a corn trypsin inhibitor overexpressed in Escherichia coli.

The cDNA of a 14-kDa trypsin inhibitor (TI) from corn was subcloned into an Escherichia coli overexpression vector. The overexpressed TI was purified based on its insolubility in urea and then refolded into the active form in vitro. This recombinant TI inhibited both conidium germination and hyphal growth of all nine plant pathogenic fungi studied, including Aspergillus flavus, Aspergillus parasiticus, and Fusarium moniliforme. The calculated 50% inhibitory concentration of TI for conidium germination ranged from 70 to more than 300 microgram/ml, and that for fungal growth ranged from 33 to 124 microgram/ml depending on the fungal species. It also inhibited A. flavus and F. moniliforme simultaneously when they were tested together. The results suggest that the corn 14-kDa TI may function in host resistance against a variety of fungal pathogens of crops.

Aspergillus flavus↗

Distribution of antifungal proteins in maize kernel tissues using immunochemistry.

This study examined the distribution of two antifungal proteins, ribosome-inactivating protein (RIP) and zeamatin, in maize kernel tissues. Proteins were extracted from endosperm (including aleurone layer) and embryo tissues of imbibed maize kernels. Western blot analyses revealed that RIP-like protein was present at higher levels in endosperm than in embryo tissues, whereas zeamatin-like protein was more concentrated in embryo tissues than in endosperm tissues. However, there were three protein bands in the endosperm and two bands in the embryo that reacted to anti-RIP antibody in Western blot analyses. Tissue prints were conducted to localize the antifungal proteins. Imbibed kernels were cut longitudinally and transversely and blotted onto nitrocellulose membranes. Using antibodies against maize RIP and zeamatin, RIP was found primarily in the aleurone layer of the endosperm and glandular layer of scutellum, whereas zeamatin was located mainly in the kernel embryo. These results provide insight into the potential functions of these antifungal proteins, especially since the presence of RIP and zeamatin within maize kernels uniquely protects kernels from pathogens.

Aflatoxins↗

Primary care practice adherence to National Cholesterol Education Program guidelines for patients with coronary heart disease.

BACKGROUND: Clinical trials demonstrate significant benefit from cholesterol management for patients with cardiovascular disease (CVD). National guidelines recommending goals for screening and treatment were published in 1993 and widely disseminated. This study examines cholesterol screening and management by primary care physicians after the guidelines were released. METHODS: Medical records and patient surveys provided data for 603 patients with CVD, aged 27 to 70 years, from 45 practices in 4 states during 1993 to 1995. Physician surveys measured estimated performance and other variables. Physician and patient factors associated with adherence, or lack of adherence, to national guidelines were examined using univariate and multivariate analyses. RESULTS: A total of 199 patients (33%) with CVD were not screened with lipid panels, 271 patients (45%) were not receiving dietary counseling, and 404 (67%) were not receiving cholesterol medication. Only 84 patients (14%) with CVD had achieved the recommended low-density lipoprotein level of less than 2.58 mmol/L (100 mg/dL) and 302 (50%) had triglyceride levels lower than 2.26 mmol/L (200 mg/dL). Patients with a revascularization history and higher low-density lipoprotein and/or triglyceride levels were more likely to receive treatment, but other patient factors, including CVD risk factors, did not predict treatment. Physician specialty was not associated with differences in treatment, but physicians in practice for fewer years ordered more lipid panels. CONCLUSIONS: Most patients with CVD in primary care were not receiving cholesterol screening and management as recommended by the National Cholesterol Education Program guidelines in the 2 years after their release. Increasing cholesterol screening and treatment should be a priority for practice quality improvement and could result in significant reductions in CVD events for high-risk patients.

Adult↗

Movement of gating machinery during the activation of rod cyclic nucleotide-gated channels.

In the visual and olfactory systems, cyclic nucleotide-gated (CNG) ion channels convert stimulus-induced changes in the internal concentrations of cGMP and cAMP into changes in membrane potential. Although it is known that significant activation of these channels requires the binding of three or more molecules of ligand, the detailed molecular mechanism remains obscure. We have probed the structural changes that occur during channel activation by using sulfhydryl-reactive methanethiosulfonate (MTS) reagents and N-ethylmaleimide (NEM). When expressed in Xenopus oocytes, the alpha-subunit of the bovine retinal channel forms homomultimeric channels that are activated by cGMP with a K1/2 of approximately 100 microM. Cyclic AMP, on the other hand, is a very poor activator; a saturating concentration elicits only 1% of the maximum current produced by cGMP. Treatment of excised patches with MTS-ethyltrimethylamine (MTSET) or NEM dramatically potentiated the channel's response to both cyclic nucleotides. After MTSET treatment, the dose-response relation for cGMP was shifted by over two orders of magnitude to lower concentrations. The effect on channel activation by cAMP was even more striking. After modification, the channels were fully activated by cAMP with a K1/2 of approximately 60 microM. This potentiation was abolished by conversion of Cys481 to a nonreactive alanine residue. Potentiation occurred more rapidly in the presence of saturating cGMP, indicating that this region of the channel is more accessible when the channel is open. Cys481 is located in a linker region between the transmembrane and cGMP-binding domains of the channel. These results suggest that this region of the channel undergoes significant movement during the activation process and is critical for coupling ligand binding to pore opening. Potentiation, however, is not mediated by the recently reported interaction between the amino- and carboxy-terminal regions of the alpha-subunit. Deletion of the entire amino-terminal domain had little effect on potentiation by MTSET.

Animals↗

Pediatric head and neck lesions.

Commonly encountered head and neck lesions in children are described with an emphasis on evaluation, diagnosis, and treatment. Congenital lesions typically require excision, although hemangiomas usually resolve spontaneously. Acute suppurative lymphadenitis is common and readily diagnosed. Chronic lymphardenitis remains a diagnostic challenge and must be differentiated from malignancy. Lesions that do not respond to antibiotics should be biopsied to exclude neoplasms.

Branchioma↗

Care of the surgical intensive care nursery graduate. The primary care pediatrician's perspective.

Care of the intensive care nursery graduate may be quite challenging. It is important that primary care pediatricians become familiar with the complications unique to surgical patients so that they may properly prepare and educate parents and provide appropriate long-term follow-up for these often complex patients. Maintenance of a close relationship with the pediatric surgeon with an open line of communication regarding the approach to various surgical problems facilitates the effective integration of the intensive care nursery graduate into the primary care pediatrician's practice and provides the foundation for a successful clinical outcome.

Algorithms↗