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Biomedical subjects

D R Brown

Publications and source records attributed to D R Brown.

At least 253 records · Page 14Linked to original sources
PubMed1993

Analysis of the promoter sequences of the UL9 gene of herpes simplex virus type 1.

The origin-binding protein, encoded by the UL9 gene of herpes simplex virus-1 (HSV-1), has the properties of an initiator of DNA replication. Since onset of lytic replication of the virus can be critically controlled by availability of the initiator protein, we have analyzed the sequences upstream of the UL9 gene in a monkey kidney cell line (Vero). In this communication, we report the presence of three UL9 transcripts and multiple transcription initiation sites of the UL9 gene in HSV-1-infected cells. The presence of multiple transcription initiation sites for the UL9 gene is consistent with the absence of a TATA element 5'- to the UL9 ORF. A 395-bp upstream sequence encompassing all UL9 transcription initiation sites was active in expressing a reporter gene and was induced by viral immediate-early proteins. This result is consistent with the earlier observation that immediate-early proteins of HSV-1 induce viral early genes.

Animals↗
PubMed1993

Detection of human papillomavirus L1 protein in condylomata acuminata from adults with defects in cell-mediated immunity.

Immunohistochemical assays for human papillomavirus (HPV) L1 protein, using antiserum directed against the L1 major capsid protein of bovine papillomavirus (anti-BPV serum), were performed on 101 condylomata acuminata biopsy samples from 47 men (40 of whom had intact cell mediated immunity [CMI], and 7 with conditions known to cause CMI defects), and 54 women (48 with normal CMI, and 6 with CMI defects). L1 protein was detected in 28% of all biopsies, including 20.5% of samples from patients with normal CMI and 76.9% of patients with CMI defects (P = .00002). For both males and females, L1 protein was detected significantly more often in samples from patients with CMI defects than those with normal CMI. Immunohistochemical assays of HPV 11-infected human foreskin implants grown in athymic mice were performed to optimize the conditions of the assay. Three dilutions of anti-BPV serum or preimmune rabbit serum were used. A 1:500 dilution provided readily interpretable results, while preimmune serum at this dilution did not stain to any significant degree. However, at 1:10 and 1:100 dilution, both the anti-BPV serum and preimmune serum caused an unacceptable amount of nuclear staining, making results uninterpretable. Defects in CMI may allow active viral particle assembly at an increased rate, as judged by detection of L1 protein in condylomata acuminata from these patients.

Capsid↗
PubMed1993

Selective hyperresponsiveness to ovalbumin-induced epithelial transport in inflamed guinea pig distal colon.

This study examined whether a mild inflammatory state induced by acetic acid would alter ovalbumin-induced motor and secretory responses of the actively sensitized colon. Short-circuit current (Isc), a measure of active transepithelial ion transport, and longitudinal contractility were measured, respectively, in mucosa-submucosa or smooth muscle sheets from guinea pig distal colon. Ovalbumin produced similar, concentration-dependent increases in Isc in noninflamed and inflamed colonic mucosa. Chlorpheniramine, an H1-histamine antagonist, produced a concentration-related decrease in antigen efficacy that was greater in noninflamed mucosa than in inflamed tissues. Lipoxygenase inhibitors (R840 and A64077) were equally effective in decreasing ovalbumin-induced secretion in both inflamed and noninflamed tissues. Ovalbumin also produced longitudinal muscle contractions that were of similar magnitude in inflamed and noninflamed strips. Moreover, chlorpheniramine and lipoxygenase inhibitors inhibited contractile responses in muscle from both inflamed and noninflamed colons. These results suggest that inflammation produces hyperresponsiveness in the colonic mucosa but not in the underlying longitudinal smooth muscle.

Animals↗
PubMed1993

Design of a device to exercise hip extensor muscles in children with cerebral palsy.

Children with cerebral palsy (CP) often have weak hip extensor muscles and gait-related difficulties. Current therapeutic techniques do not provide sufficient exercise for this muscle group. In addition to calisthenics, therapists use a traditional tricycle to strengthen leg muscles, yet the mechanics of traditional tricycles are not effective in exercising hip extensor muscles. A new therapeutic tricycle was designed specifically to exercise the hip extensor muscles, and tests compared the traditional tricycle to the new hip extensor tricycle in effectiveness of promoting hip extensor activity in two subjects without CP. The tests demonstrated that the hip extensor tricycle was more effective in promoting hip extensor activity. Tests are underway to investigate the effect of the hip extensor tricycle in improving hip extensor strength and gait in patients with cerebral palsy. This paper describes the design of the hip extensor tricycle and a preliminary investigation of its effectiveness.

Cerebral Palsy↗
PubMed1993

Evaluation of the hip-extensor tricycle in improving gait in children with cerebral palsy.

Weakness of the hip extensor muscles contributes to the walking impairment of children with cerebral palsy, but it is difficult to strengthen these muscles. This study demonstrates greater activation of the hip extensor muscles when using a tricycle developed for this purpose than when using a traditional tricycle. The hip-extensor tricycle was also found to be more stable than a traditional tricycle. A 10-week field trial of the hip-extensor tricycle showed that visually analysed gait improved, but hip extensor strength did not. However, children used and enjoyed the tricycle, and parental reports were positive. This tricycle could be used to supplement other means of improving gait in children with CP.

Bicycling↗
PubMed1993

A physiologically based pharmacokinetic assessment of tetrachloroethylene in groundwater for a bathing and showering determination.

A two-step methodology is described to make a health-based determination for the bathing and showering use of the water from a private well contaminated with volatile organic chemicals. The chemical perchloroethylene (PERC) is utilized to illustrate the approach. First, a chemical-specific exposure model is used to predict the concentration of PERC in the shower air, shower water, and in the air above the bathtub. Second, a physiologically based pharmacokinetic (PBPK) model is used to predict the concentration of PERC delivered to the target tissue, the brain, since the focus is on neurological endpoints. The simulation exercise includes concurrent dermal and inhalation routes of exposure. A reference target tissue level (RTTL) in the brain is estimated using the PBPK model. A hazard index based on this benchmark guideline is used to make a regulatory determination for bathing and showering use of the contaminated water.

Baths↗
PubMed1993

Analysis of human papillomavirus types in exophytic condylomata acuminata by hybrid capture and Southern blot techniques.

Exophytic condylomata acuminata of the external genitalia of 40 patients were analyzed for human papillomavirus (HPV) DNA by the Southern blot and hybrid capture methods. All lesions were initially analyzed by the Southern blot method by using a mixture of HPV type 6, 11, 16, and 18 whole genomic probes. Southern blots demonstrated characteristic PstI restriction patterns of HPV type 6, 11, or 16 in all but one lesion. HPV 6 subtypes accounted for 28 of 39 HPV-positive lesions. Twenty-seven of these 28 lesions contained HPV type 6a, and 1 lesion contained HPV type 6c. Eight lesions contained HPV type 11 and three contained HPV type 16. Two of the three condylomata acuminata containing HPV type 16 were obtained from solid-organ transplant recipients receiving immunosuppressive medications. The third lesion containing HPV type 16 was a typical exophytic condyloma acuminatum from a woman with previously resected vulvar carcinoma. The hybrid capture assay detected HPV DNAs in all lesions except the Southern blot-negative lesion. Twenty-five lesions were positive for the A probe only (HPV types 6 and 11 and related types). All of these lesions were found to contain HPV type 6 or 11 sequences in the Southern blot assay. The remaining 14 lesions were positive for both the A probe and the B probe (HPV types 16 and 18 and related types). The strongest signal in these 14 lesions by the hybrid capture assay was consistent with the result of the Southern blot assay in all but one case. We conclude that (i) HPV type 6a is the most common type found in these lesions, (ii) HPV type 16 may be present more often in exophytic condylomata acuminata from immunosuppressed individuals, (iii) hybrid capture is a useful tool for documenting the presence of HPV sequences in DNAs from exophytic condylomata acuminata, and (iv) in samples containing multiple HPV types, hybrid capture allows detection of minority HPV types.

Blotting, Southern↗
PubMed1993

The tumor suppressor p53 and the oncoprotein simian virus 40 T antigen bind to overlapping domains on the MDM2 protein.

The oncogene mdm2 has been found to be amplified in human sarcomas, and the gene product binds to the tumor suppressor p53. In this report, we describe the dissection of the MDM2-binding domain on p53 as well as the p53-binding domain on MDM2. We also demonstrate that the oncoprotein simian virus 40 T antigen binds to the product of cellular oncogene mdm2. We have constructed several N- and C-terminal deletion mutants of p53 and MDM2, expressed them in vitro, and assayed their in vitro association capability. The N-terminal boundary of the p53-binding domain on MDM2 is between amino acids 1 and 58, while the C-terminal boundary is between amino acids 221 and 155. T antigen binds to an overlapping domain on the MDM2 protein. On the other hand, the MDM2-binding domain of p53 is defined by amino acids 1 and 159 at the N terminus. At the C terminus, binding is progressively reduced as amino acids 327 to 145 are deleted. We determined the effect of human MDM2 on the transactivation ability of wild-type human p53 in the Saos-2 osteosarcoma cell line, which does not have any endogenous p53. Human MDM2 inhibited the ability of human p53 to transactivate the promoter with p53-binding sites. Thus, human MDM2 protein, like the murine protein, can inactivate the transactivation ability of human p53. Interestingly, both the transactivation domain and the MDM2-binding domain of p53 are situated near the N terminus. We further show that deletion of the N-terminal 58 amino acids of MDM2, which eliminates p53 binding, also abolishes the capability of inactivating p53-mediated transactivation. This finding suggests a correlation of in vitro p53-MDM2 binding with MDM2's ability in vivo to interfere with p53-mediated transactivation.

Amino Acid Sequence↗
PubMed1993

Breathing periodicity in intact and carotid body-denervated ponies during normoxia and chronic hypoxia.

Periodic oscillations in pulmonary ventilation (VI), tidal volume (VT), and inspiratory and expiratory times (TI and TE) were studied during normoxia (arterial PO2 = 95 Torr) and 48 h of hypoxia (arterial PO2 = 40-50 Torr) in awake intact (n = 8) and carotid body-denervated (CBD; n = 8) ponies. Periodic oscillations were identified by fast-Fourier transformation of breath-by-breath data and quantitated by determining the power ratio of significant periodic oscillations to total power of data sequence. Periodic oscillations of 0.063-0.500 cycles/breath were observed in all parameters during both normoxia and hypoxia. During normoxia, CBD accentuated periodicity of VT (P < 0.02) and VI (P < 0.01) but did not change TI or TE periodicity (P > 0.05). These findings suggest that carotid chemoreceptors serve to stabilize breathing (i.e., decrease periodicity) during normoxia, conceivably because of their shorter response time compared with that of central chemoreceptors. During certain periods of hypoxia, periodicity of VT and VI was significantly (P < 0.05) increased in intact ponies. The response to hypoxia in CBD ponies was variable, with VI periodicity significantly (P < 0.05) increasing, decreasing, or unchanging. Because some CBD ponies significantly changed their periodicity during hypoxia compared with normoxia, we conclude that carotid chemoreceptors are not requisite for hypoxia-induced changes in periodic breathing. In addition, our observations in both groups of ponies during normoxia and hypoxia suggest that multiple mechanisms may lead to periodic oscillations in breathing.

Animals↗
PubMed1993

Clinical appropriateness, therapeutic equivalence, and cost of conversion of H2 antagonist therapy.

A 12-month drug monitoring program targeting the use of H2 antagonists was initiated at the Erie County Medical Center, a 650-bed academic teaching hospital in Buffalo, NY. Discussed in this article are the development of indicators used to determine appropriateness of therapy, implementation of a H2 antagonist monitoring and screening program, examination of the effect of the program on budgetary expenditures for H2 antagonist therapy, evaluation of adverse effects and potential drug interactions associated with drug use, and measurement of possible drug cost savings resulting from the implementation of the program.

Cimetidine↗
PubMed1993

Molecular characterization of alpha 2-adrenergic receptors regulating intestinal electrolyte transport.

Norepinephrine (NE) is an important neuromodulator of active Na+ and Cl- transport by the small intestine; however, the cellular targets and the adrenergic receptor (AR) subtype mediating its effects on ion transport have not been clearly defined. NE inhibited short-circuit current in submucosal-mucosal sheets of porcine distal jejunum under basal conditions and after electrical transmural stimulation of intrinsic neurons. A membrane fraction (P2) prepared from the submucosa of porcine jejunum was enriched in specific [3H]saxitoxin binding sites, relative to other submucosal fractions. This fraction contained homogeneous and high affinity sites binding the alpha 2-AR antagonist [3H]yohimbine (Kd = 0.39 +/- 0.03 nM). A prazosin versus oxymetazoline Ki ratio of 218 was obtained for the submucosal AR binding site, suggesting that it represents a neuronal alpha 2A-AR. A cell membrane fraction prepared from the mucosa exhibited specific and saturable high affinity binding of the muscarinic cholinergic antagonist [3H] quinuclidinyl benzilate (Kd = 77 +/- 9 pM) but displayed minimal specific binding of [3H]saxitoxin or [3H]yohimbine. A [32P]cDNA probe derived from the human alpha 2-C10 gene encoding the alpha 2A-AR hybridized to a 3.8-kilobase message that was prevalent in poly(A)+ RNA isolated from the jejuno-ileal submucosa and was also detected in porcine cerebral cortex and kidney; no message was detected in RNA isolated from the jejunal mucosa. These results suggest that NE modulates active ion transport in the small intestine through interactions with a submucosal alpha 2A-AR probably associated with enteric neurons.

Animals↗
PubMed1993

Neurally mediated actions of leukotrienes on ion transport in guinea pig distal colon.

The effects of the sulfidopeptide leukotrienes (LT), LTC4, LTD4 and LTE4 on short-circuit current (Isc), a measure of active ion transport, were determined in muscle-stripped mucosa sheets from the guinea pig distal colon. LTC4 and D4, but not E4, evoked concentration-dependent increases in Isc. Auto- and cross-tachyphylaxis could be demonstrated in LT actions. LTD4 was more sensitive than LTC4 to inhibition by the LTD4 antagonist, 1-<2-hydroxy-3-propyl-4-<4-(1H-tetrazol-5-yl)butoxy>phenyl>etha none, and the intracellular Ca++ inhibitor, 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester. Mucosal LT effects were reduced in tissues pretreated with bumetanide or bathed in HCO3(-)-free media. Measurements of transepithelial Na+ and Cl- fluxes revealed that LTC4 increased unidirectional and net secretory fluxes of Cl- but had no effect on Na+ transport. Tetrodotoxin, atropine and indomethacin inhibited mucosal responses to LTC4 and D4; in addition prazosin inhibited LTD4 effects. The results suggest that LTC4 and D4 evoke anion secretion by acting through distinct LT receptor populations. These effects are mediated in part by cholinergic and adrenergic submucosal neurons as well as by colonic prostanoids.

Adrenergic alpha-Antagonists↗
PubMed1993

Effects of inflammatory mediators on electrolyte transport across the porcine distal colon epithelium.

The epithelium from the porcine distal colon was mounted in Ussing chambers and bathed in plasma-like Ringer's solution. Histamine produced increases in current which were not affected by pretreatment with the neural conduction blocker tetrodotoxin. Both the H1-histamine antagonist pyrilamine and the cyclooxygenase inhibitor indomethacin produced dextral shifts in the histamine concentration-response curve. Replacement of Cl with gluconate or HCO3 with tris(hydroxymethyl)aminomethane(tris)-N-2- hydroxyethylpiperazine-N'-2-ethanesulfonic acid in the bathing solution inhibited the mucosal response to histamine by 74 and 23%, respectively. In addition, histamine increased the serosal-to-mucosal Na and Cl fluxes and inhibited the mucosal-to-serosal Na flux, resulting in a reduction of net Na and Cl absorption. Prostaglandin E2 also produced increases in short-circuit current which remained unaffected by tetrodotoxin. Replacement of either Cl or HCO3 inhibited these increases by 85%. Prostaglandin E2 inhibited the mucosal-to-serosal and net Cl fluxes. Leukotriene C4 produced oscillating increases in the short-circuit current which were completely blocked by tetrodotoxin. These increases in current were attributed to an increase in the serosal-to-mucosal Cl flux which resulted in a decrease in net Cl absorption. From these data it was concluded that: 1) histamine interacts with H1-receptors to increase Na and Cl secretion and inhibit Cl absorption; 2) prostaglandin E2 inhibits a HCO3-dependent Cl absorptive pathway, possibly involving Cl/HCO3 exchange and 3) leukotriene C4 acts on enteric nerves to stimulate Cl secretion.

Animals↗
PubMed1993

Effects of exercise and rest on the state anxiety and blood pressure of physically challenged college students.

The purpose of this study was to evaluate the effects of a single session of exercise and quiet rest on the blood pressure and state anxiety response of physically challenged college students (n = 10) enrolled in an adaptive physical education class. Each student had some degree of injury or disability (none requiring the use of a wheelchair) which made exercising inconvenient with regard to maintaining an optimal level of frequency, intensity, and duration of activity. All subjects participated in two treatment conditions in a counter-balanced design: (1) exercise (on a bicycle ergometer or treadmill) to self-imposed maximum, and (2) quiet rest in a soundproof chamber. Blood pressure and state anxiety (STAI 1) were assessed prior to and immediately following both conditions. A repeated measures ANOVA was used to analyze the data. There was a non-significant 7.4 mmHg increase in systolic blood pressure immediately following exercise, and a 9.6 mmHg, decrease following rest. A significant decrease in state anxiety was observed following exercise and rest. It is concluded that individuals who are physically challenged can experience reductions in anxiety after a session of vigorous exercise.

Adult↗
PubMed1992

Blood pressure increases in response to feeding in the term neonate.

We studied blood pressure and heart rate of 18 medically well newborn babies before, during, and after feeding. Seven were breast-fed and 11 bottle-fed and all were studied between 24 and 92 hr of age. There was an increase in heart rate associated with sucking on a pacifier but no additional increase with feeding. By 30-60 min after feeding, heart rate had returned to baseline value. Blood pressure, however, did increase in response to feeding and showed a greater increase in the breast-fed group than in the bottle-fed group. Systolic blood pressure rose from 72 mmHg in the basal state to 85 mmHg during the first 3 min of feeding in the bottle-fed babies and from 73 to 99 mmHg during comparable periods in the breast-fed babies. The results for diastolic blood pressure were similar except that changes within the bottle-fed group were not statistically significant. Bottle-fed babies rose only from 42 to 47 mmHg while breast-fed babies rose from 42 to 61 mmHg from basal conditions to feeding. Blood pressure responses to feeding may have implications for susceptibility to necrotizing enterocolitis, for future blood pressure liability in adulthood and for later hypertensive disease.

Arousal↗
PubMed1992

A model for an outpatient imaging center.

U.S. federally imposed efforts to regulate joint venturing are a result of certain physician strategies to circumvent anti-kickback statutes by investing in clinics, labs, and facilities for self-referral. This article addresses the ethical debate on physician ownership, MRI as an evolving modality, the 1989 Ethics in Patient Referrals Act and the subsequently released "safe harbors," and finally, describes an existing model for physician/hospital ownership in an outpatient MRI facility.

Ethics, Medical↗