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Biomedical subjects

J D Brown

Publications and source records attributed to J D Brown.

At least 37 records · Page 2Linked to original sources
PubMed2000

An algorithm for predicting proton nuclear magnetic resonance deshielding over a carbon-carbon double bond.

Hydrogen nuclei located over a carbon-carbon double bond in a strong magnetic field experience NMR shielding effects that result from the magnetic anisotropy of the nearby double bond and various other intramolecular shielding effects. We have used GIAO, a subroutine in Gaussian 98, to calculate isotropic shielding values and to predict the proton NMR shielding increment for a simple model system: methane held in various orientations, positions, and distances over ethene. The average proton NMR shielding increments of several orientations of methane have been plotted versus the Cartesian coordinates of the methane protons relative to the center of ethene. A single empirical equation for predicting the NMR shielding experienced by protons over a carbon-carbon double bond has been developed from these data. The predictive capability of this equation has been validated by comparing the shielding increments for several alkenes calculated using our equation to the experimentally observed shielding increments. This equation predicts the NMR shielding effects more accurately than previous models that were based on fewer geometries of methane over ethene. In fact, deshielding is predicted by this equation for protons over the center and within about 3 A of a carbon-carbon double bond. This result is in sharp contrast to predictions made by the long-held McConnell "shielding cone" model found in nearly every textbook on NMR, but is consistent with experimental observations. The algorithm for predicting the (de)shielding increment for a proton over an alkene can be used in a spreadsheet on a PC or incorporated into software that estimates chemical shifts using additive substituent constants or a database of structures. In either application its use can substantially improve the accuracy of the estimated chemical shift of a proton in the vicinity of a carbon-carbon double bond, and thus assist in spectral assignments and in correct structure determination.

Algorithms↗
PubMed2000

The development of a post-baccalaureate certificate program in molecular diagnostics.

A post-baccalaureate certificate program in diagnostic molecular sciences was created in 1995 by the Diagnostic Genetic Sciences Program in the School of Allied Health at the University of Connecticut. The required on-campus lecture and laboratory courses include basic laboratory techniques, health care issues, cell biology, immunology, human genetics, research, management, and molecular diagnostic techniques and laboratory in molecular diagnostics. These courses precede a 6-month, full-time practicum at an affiliated full-service molecular laboratory. The practicum includes amplification and blotting methods, a research project, and a choice of specialized electives including DNA sequencing, mutagenesis, in situ hybridization methods, or molecular diagnostic applications in microbiology. Graduates of the program are immediately eligible to sit for the National Credentialing Agency examination in molecular biology to obtain the credential Clinical Laboratory Specialist in Molecular Biology (CLSp(MB). This description of the University of Connecticut program may assist other laboratory science programs in creating similar curricula.

Connecticut↗
PubMed2000

Handshaking, gender, personality, and first impressions.

Although people's handshakes are thought to reflect their personality and influence our first impressions of them, these relations have seldom been formally investigated. One hundred twelve participants had their hand shaken twice by 4 trained coders (2 men and 2 women) and completed 4 personality measures. The participants' handshakes were stable and consistent across time and coders. There were also gender differences on most of the handshaking characteristics. A firm handshake was related positively to extraversion and emotional expressiveness and negatively to shyness and neuroticism; it was also positively related to openness to experience, but only for women. Finally, handshake characteristics were related to the impressions of the participants formed by the coders. These results demonstrate that personality traits, assessed through self-report, can predict specific behaviors assessed by trained observers. The pattern of relations among openness, gender, handshaking, and first impressions suggests that a firm handshake may be an effective form of self-promotion for women.

Adult↗
PubMed2000

The maternal Xenopus beta-catenin signaling pathway, activated by frizzled homologs, induces goosecoid in a cell non-autonomous manner.

In spite of abundant evidence that Wnts play essential roles in embryonic induction and patterning, little is known about the expression or activities of Wnt receptors during embryogenesis. The isolation and expression of two maternal Xenopus frizzled genes, Xfrizzled-1 and Xfrizzled-7, is described. It is also demonstrated that both can activate the Wnt/beta-catenin signaling pathway as monitored by the induction of specific target genes. Activation of the beta-Catenin pathway has previously been shown to be necessary and sufficient for specifying the dorsal axis of Xenopus. beta-Catenin is thought to work through the cell-autonomous induction of the homeobox genes siamois and twin, that in turn bind to and activate the promoter of another homeobox gene, goosecoid. However, it was found that the beta-catenin pathway regulated the expression of both endogenous goosecoid, and a goosecoid promoter construct, in a cell non-autonomous manner. These data demonstrate that maternal Frizzleds can activate the Wnt/beta-catenin pathway in Xenopus embryos, and that induction of a known downstream gene can occur in a cell non-autonomous manner.

Amino Acid Sequence↗
PubMed2000

Cardiovascular responses during prolonged exercise at ventilatory threshold in boys and men.

PURPOSE: The purpose of this study was to examine the cardiovascular responses during prolonged exercise in boys and men at an intensity set relative to ventilatory threshold (VT). METHODS: Eight boys (10-13 yr) and 10 men (18-25 yr) completed an orientation trial, a maximal exercise test, and a 40-min submaximal exercise bout at an intensity equal to the VO2 at VT (approximately 64.5% VO2max). RESULTS: Heart rate (HR) was higher and stroke volume (SV) was lower in the boys compared with the men (P < or = 0.05). From 10 to 40 min, HR significantly increased 9.5% and 13.6% and SV significantly decreased 8.8% and 11.6% in the boys and men, respectively. Despite the tendency for the changes in HR and SV to be greater in the men, the group-by-time interaction was not significant. Cardiac output was greater in the men (P < or = 0.05) but remained constant over time (P > 0.05). In men, mean arterial blood pressure was higher (P < or = 0.05) and decreased 4.2% over time. In boys, mean arterial blood pressure remained constant, which resulted in a significant group-by-time interaction. Total peripheral resistance (TPR) was significantly higher in the boys and remained constant over time (P > 0.05). From 0 to 40 min, the decrease in plasma volume was significantly greater in the men (-10.2%) than the boys (-5.7%) but was unrelated to the changes in SV in either group (P > 0.05). CONCLUSION: In conclusion, the cardiovascular responses during prolonged exercise are similar in boys and men, although there is a tendency for the magnitude of cardiovascular drift to be greater in the men.

Adolescent↗
PubMed1999

Mechanism and function of signal transduction by the Wnt/beta-catenin and Wnt/Ca2+ pathways.

Communication between cells is often mediated by secreted signaling molecules that bind cell surface receptors and modulate the activity of specific intracellular effectors. The Wnt family of secreted glycoproteins is one group of signaling molecules that has been shown to control a variety of developmental processes including cell fate specification, cell proliferation, cell polarity and cell migration. In addition, mis-regulation of Wnt signaling can cause developmental defects and is implicated in the genesis of several human cancers. The importance of Wnt signaling in development and in clinical pathologies is underscored by the large number of primary research papers examining various aspects of Wnt signaling that have been published in the past several years. In this review, we will present a synopsis of current research with particular attention paid to molecular mechanism of Wnt signal transduction and how the mis-regulation of Wnt signaling leads to cancer.

Aging↗
PubMed1999

MEKK-1, a component of the stress (stress-activated protein kinase/c-Jun N-terminal kinase) pathway, can selectively activate Smad2-mediated transcriptional activation in endothelial cells.

Smad proteins are essential components of the intracellular signaling pathways utilized by members of the transforming growth factor-beta (TGF-beta) superfamily of growth factors. Certain Smad proteins (e.g. Smad1, -2, and -3) can act as regulated transcriptional activators, a process that involves phosphorylation of these proteins by activated TGF-beta superfamily receptors. We demonstrate that the intracellular kinase mitogen-activated protein kinase kinase kinase-1 (MEKK-1), an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase pathway, can participate in Smad2-dependent transcriptional events in cultured endothelial cells. A constitutively active form of MEKK-1 but not mitogen-activated protein kinase kinase-1 (MEK-1) or TGF-beta-activated kinase-1, two distinct intracellular kinases, can specifically activate a Gal4-Smad2 fusion protein, and this effect correlates with an increase in the phosphorylation state of the Smad2 protein. These effects do not require the presence of the C-terminal SSXS motif of Smad2 that is the site of TGF-beta type 1 receptor-mediated phosphorylation. Activation of Smad2 by active MEKK-1 results in enhanced Smad2-Smad4 interactions, nuclear localization of Smad2 and Smad4, and the stimulation of Smad protein-transcriptional coactivator interactions in endothelial cells. Overexpression of Smad7 can inhibit the MEKK-1-mediated stimulation of Smad2 transcriptional activity. A physiological level of fluid shear stress, a known activator of endogenous MEKK-1 activity in endothelial cells, can stimulate Smad2-mediated transcriptional activity. These data demonstrate a novel mechanism for activation of Smad protein-mediated signaling in endothelial cells and suggest that Smad2 may act as an integrator of diverse stimuli in these cells.

Animals↗
PubMed1999

Community-acquired methicillin-resistant Staphylococcus aureus in hospitalized adults and children without known risk factors.

Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections are not commonly recognized in healthy patients without predisposing risk. We performed a retrospective study of patients hospitalized with community-acquired MRSA infections from 1992 to 1996 in Honolulu to determine if community-acquired MRSA infections occurred in patients without known risk. Patients hospitalized within the previous 6 months or transferred from other hospitals or nursing homes were excluded. Epidemiological and clinical data were obtained from an inpatient chart review. Ten (71%) of 14 patients with community-acquired MRSA infection had no discernible characteristics of MRSA infections. Thirteen (93%) patients had skin or soft-tissue infections and one patient had MRSA pneumonia. Isolates from patients with MRSA infection were more likely to be susceptible to ciprofloxacin (P = .05), clindamycin (P = .03), and erythromycin (P = .01) than were those from MRSA-colonized patients. In our population, the majority of community-acquired MRSA infections occurred in previously healthy individuals without characteristics suggestive of MRSA transmission.

Adolescent↗
PubMed1999

XCtBP is a XTcf-3 co-repressor with roles throughout Xenopus development.

XTcf-3 is an HMG box transcription factor that mediates Xenopus dorsal-ventral axis formation. As a Wnt pathway effector, XTcf-3 interacts with beta-catenin and activates the expression of the dorsal organizing gene siamois, while in the absence of beta-catenin, XTcf-3 functions as a transcriptional repressor. We show that XTcf-3 contains amino- and carboxy-terminal repressor domains and have identified a Xenopus member of the C-terminal Binding Protein family of transcriptional co-repressors (XCtBP) as the C-terminal co-repressor. We show that two XCtBP binding sites near the XTcf-3 carboxy-terminus are required for the interaction of XTcf-3 and XCtBP and for the transcriptional repression mediated by the XTcf-3 carboxy-terminal domain. By fusing the GAL4 activation domain to XCtBP we have generated an antimorphic protein, XCtBP/G4A, that activates siamois transcription through an interaction with endogenous XTcf-3. Ectopic expression of XCtBP/G4A demonstrates that XCtBP functions in the regulation of head and notochord development. Our data support a role for XCtBP as a co-repressor throughout Xenopus development and indicate that XCtBP/G4A will be a useful tool in determining how XCtBP functions in various developmental processes.

Amino Acid Sequence↗
PubMed1999

Failure to confirm the Rauscher and Shaw description of recovery of the Mozart effect.

The Mozart effect is an increase in spatial reasoning scores detected immediately after listening to the first movement of a Mozart piano sonata. Rauscher and Shaw (1998) suggested that failure to produce a Mozart effect could arise from carryover effects of a spatial reasoning pretest which may interfere with the effect of listening to Mozart. They cited an unpublished study in which a verbal distractor was inserted between the pretest and listening condition, and the manipulation produced the recovery of a Mozart effect. This experiment attempted to confirm the unpublished study. 206 college students were exposed to one of three sequences, pretest-Verbal distractor material-Mozart, pretest-Mozart-Verbal distractor material, and pretest-Verbal distractor material. An immediate posttest indicated no significant difference on solution of paper folding and cutting items among the three groups. The results do not support Rauscher and Shaw (1998). Our negative results are consistent with prior failures in other laboratories to produce a Mozart effect.

Attention↗
PubMed1999

An outbreak of acute eosinophilic myositis attributed to human Sarcocystis parasitism.

Seven members of a 15-man U.S. military team that had operated in rural Malaysia developed an acute illness consisting of fever, myalgias, bronchospasm, fleeting pruritic rashes, transient lymphadenopathy, and subcutaneous nodules associated with eosinophilia, elevated erythrocyte sedimentation rate, and elevated levels of muscle creatinine kinase. Sarcocysts of an unidentified Sarcocystis species were found in skeletal muscle biopsies of the index case. Albendazole ameliorated symptoms in the index case; however, his symptoms persisted for more than 5 years. Symptoms in 5 other men were mild to moderate and self-limited, and 1 team member with laboratory abnormalities was asymptomatic. Of 8 team members tested for antibody to Sarcocystis, 6 were positive; of 4 with the eosinophilic myositis syndrome who were tested, all were positive. We attribute this outbreak of eosinophilic myositis to accidental tissue parasitism by Sarcocystis.

Acute Disease↗
PubMed1999

Late traumatic intraocular lens extrusion after penetrating keratoplasty.

BACKGROUND: Penetrating keratoplasty places a patient at risk for wound rupture from blunt trauma because the graft-host interface remains weakened for years after the surgery. Violent environments, contact sports, and strenuous activity put patients with compromised corneal structural integrity at high risk of traumatic injury. CASE REPORT: This case report presents a 42-year-old penetrating keratoplasty patient with a history of homelessness, polysubstance abuse, and domestic violence. This patient experienced a ruptured globe at the graft-host junction secondary to a direct blow by a fist, which extruded the intraocular lens from the eye. After emergency wound closure, the graft continued to degrade until bullous keratopathy developed. With little visual recovery potential for this graft, a Gunderson conjunctival flap procedure was implemented to decrease chronic ocular pain. CONCLUSIONS: After penetrating keratoplasty, patients should be periodically reminded of the susceptibility of the graft wound to injury from high-risk activity and violence. Constant use of protective eyewear should be recommended to corneal transplant recipients.

Adult↗
PubMed1998

CREB binding protein is a required coactivator for Smad-dependent, transforming growth factor beta transcriptional responses in endothelial cells.

The transforming growth factor-beta (TGF-beta) superfamily of growth factors and cytokines has been implicated in a variety of physiological and developmental processes within the cardiovascular system. Smad proteins are a recently described family of intracellular signaling proteins that transduce signals in response to TGF-beta superfamily ligands. We demonstrate by both a mammalian two-hybrid and a biochemical approach that human Smad2 and Smad4, two essential Smad proteins involved in mediating TGF-beta transcriptional responses in endothelial and other cell types, can functionally interact with the transcriptional coactivator CREB binding protein (CBP). This interaction is specific in that it requires ligand (TGF-beta) activation and is mediated by the transcriptional activation domains of the Smad proteins. A closely related, but distinct endothelial-expressed Smad protein, Smad7, which does not activate transcription in endothelial cells, does not interact with CBP. Furthermore, Smad2,4-CBP interactions involve the COOH terminus of CBP, a region that interacts with other regulated transcription factors such as certain signal transduction and transcription proteins and nuclear receptors. Smad-CBP interactions are required for Smad-dependent TGF-beta-induced transcriptional responses in endothelial cells, as evidenced by inhibition with overexpressed 12S E1A protein and reversal of this inhibition with exogenous CBP. This report demonstrates a functional interaction between Smad proteins and an essential component of the mammalian transcriptional apparatus (CBP) and extends our insight into how Smad proteins may regulate transcriptional responses in many cell types. Thus, functional Smad-coactivator interactions may be an important locus of signal integration in endothelial cells.

Animals↗
PubMed1998

Wnt signaling: why is everything so negative?

The Wnt proteins constitute a family of secreted glycoproteins the members of which have essential signaling roles during embryogenesis. The recent identification of several new regulators of this signal transduction pathway have revealed unexpectedly intricate levels of constraint on Wnt-dependent gene activation, and studies in developing embryos and in cell culture systems have allowed a more complete understanding of the functional and biochemical interactions between components of this evolutionarily conserved pathway.

Animals↗
PubMed1998

Reliability of delta-crystallin as a marker for studies of chick lens induction.

Induction of a lens by the optic vesicle of the brain was the first demonstration of how tissue interactions could influence cell fate during development. However, recent work with amphibians has shown that the optic vesicle is not the primary inducer of lens formation. Rather, an earlier interaction between anterior neural plate and presumptive lens ectoderm appears to direct lens formation. One problem with many early experiments was the absence of an unambiguous assay for lens formation. Before being able to test whether the revised model of lens induction applies to chicken embryos, we examined the suitability of using delta-crystallin as a marker of lens formation. Although delta-crystallin is the major protein synthesized in the chick lens, one or both of the two delta-crystallin genes found in chickens is transcribed in many non-lens tissues as well. In studies of lens formation where appearance of the delta-crystallin protein is used as a positive assay, synthesis of delta-crystallin outside of the lens could make experiments difficult to interpret. Therefore, polyacrylamide gel electrophoresis, immunoblotting, and immunofluorescence were used to determine whether the delta-crystallin messenger RNA detected in non-lens tissues is translated into protein, as it is in the lens. On Coomassie-blue-stained gels of several tissues from stage-22 embryos, a prominent protein was observed that co-migrated with delta-crystallin. However, on immunoblots, none of the nonlens tissues tested contained detectable levels of delta-crystallin at this stage. By imunofluorescence, delta-crystallin was observed in Rathke's pouch and in a large area of oral ectoderm near Rathke's pouch, yet none of the cells in these non-lens tissues showed the typical elongated morphology of lens fiber cells. When presumptive lens ectoderm or other regions of ectoderm from stage-10 embryos were cultured and tested for lens differentiation, both cell elongation and delta-crystallin synthesis were observed, or neither were observed. The results suggest that delta-crystallin synthesis and cell elongation together serve as useful criteria for assessing a positive lens response.

Animals↗
PubMed1998

Venous thromboembolism associated with air travel: a report of 33 patients.

BACKGROUND: The medical literature suggests long distance travel, particularly air travel, may be a risk factor for venous thromboembolism, but the risk is poorly quantified. METHODS: We reviewed 134 records of patients hospitalized with venous thromboembolism for comments regarding recent travel. Patients who had traveled within 31 d prior to venous thromboembolism were defined as recent travelers. RESULTS: Of 134 patients records, 66 (49%) had documented inquiries regarding travel and 33 (50%) were recent air travelers. Data regarding demographics, mode of travel, day of onset of symptoms in relation to travel, and other risk factors for venous thromboembolism were abstracted from the records of the recent travelers. There were 12 (36%) travelers who had no other predisposition for venous thromboembolism. All had traveled non-stop by aircraft for 4 or more hours; none was identified as a crew-member. The median day of onset of venous thromboembolism was on travel day 4 (range: day 1-31). There were 8 (24%) patients who had onset during air travel or on the day of arrival, and 27 (82%) had onset by travel day 15. Air travel for 4 or more hours within the preceding 31 d was the most common risk factor for venous thromboembolism in our study patients and was present in 50%. This incidence is much higher than previously described, perhaps due to limiting the study population to those in which the presence or absence of travel was documented. CONCLUSION: Prospective studies are needed to better define the risk factors for venous thromboembolism among long distance air passengers and crew-members, and to determine effective preventive measures.

Adult↗
PubMed1998

A review of 79 patients with malaria seen at a military hospital in Hawaii from 1979 to 1995.

The goal of our study was to determine the epidemiological and clinical features of imported malaria seen at our military hospital in Hawaii. We reviewed the records of malaria cases seen from January 1, 1979, to December 31, 1995, and compared our results with published reviews from civilian hospitals in North America. Seventy-nine patients were diagnosed with malaria by blood smears. All acquired malaria abroad, mostly in southeast Asia. Sixty-seven percent of cases were vivax malaria, 22% were falciparum malaria, and 11% were caused by undetermined species. Common symptoms were fever (100%), alternate day fever (41%), rigors (91%), headache (59%), nausea (41%), fatigue (39%), dark urine (32%), and vomiting (31%). Ninety-one percent had fever during hospitalization, but 39% were afebrile on admission. Splenomegaly was detected in 49% of cases. The white blood cell count was normal in 65%, low in 31%, and elevated in 4% of cases. Other laboratory findings were anemia (58%), thrombocytopenia (74%), and mild hyperbilirubinemia (64%). Military physicians initially considered the diagnosis of malaria in only 54% of patients. The epidemiological features of our patients differ from those described in the civilian hospitals. Most of our patients were nonimmune, U.S.-born, military personnel infected in southeast Asia, whereas patients described in reviews from U.S. civilian hospitals were usually foreign-born civilians who were infected in Africa or India. The clinical features of malaria, and the problems of initial misdiagnosis in our patients, were similar to those reported from civilian hospitals. Military physicians, like their civilian colleagues, need more training and experience in malaria.

Adult↗