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Biomedical subjects

T Brown

Publications and source records attributed to T Brown.

At least 73 records · Page 4Linked to original sources
PubMed2001

Pyometra and uterine adenocarcinoma in a melengestrol acetate-implanted captive coati (Nasua nasua).

A 9-yr and 3-mo-old captive female coati (Nasua nasua) was implanted with melengestrol acetate for contraception for 4.5 yr prior to presentation. During her annual examination, purulent vaginal discharge and a palpably prominent uterus were identified. Ancillary diagnostic tests including hematology, cystocentesis, radiographs, and abdominal ultrasound were consistent with pyometra. An ovariohysterectomy was performed and histologic examination revealed pyometra and uterine adenocarcinoma, similar to pathology that has been associated with melengestrol acetate contraception in felids, canids, and primates. Given the potential association between melengestrol acetate and uterine pathology in this case, we recommend caution with melengestrol acetate use in procyonids.

Adenocarcinoma↗
PubMed2001

Should body size preference be a target of health promotion efforts to address the epidemic of obesity in Afro-Caribbean women?

OBJECTIVE: To determine if 1) Afro-Caribbean women prefer large body sizes, 2) the body size preference of Afro-Caribbean men and women are associated, 3) women's preferences are associated with increased risk of obesity or with weight management behaviors. DESIGN: Population samples of 314 and 487 women, ages 20-55 years, were recruited on Barbados and Dominica with response rates of 74% and 77%, respectively. Body size preferences, stress related variables, and demographic data were ascertained by questionnaire. Height and weight were also measured. On Barbados, body preference data were collected from male partners of participants, and data on intentions to perform weight management behaviors were collected from 175 women. RESULTS: Most women preferred body sizes within normal limits, although women on Dominica had a slightly larger ideal body size (IBS) than did Barbadian women (P<.05). On both islands, the size that women thought men preferred was related to their IBS (P<.0001). Likewise, IBS was associated with increased odds of being overweight (P<.001), however most overweight women (>75%) wanted to be smaller. IBS was not related to the intention to exercise or to eat high fat foods. CONCLUSIONS: It is unlikely that body size preference poses a barrier to intervention efforts to reduce the prevalence of overweight in Afro-Caribbean women.

Adult↗
PubMed2001

The impact of psychological disturbances on immediate memory.

The current study tested the hypothesis that attention mediates the impact of psychological disturbances (i.e. depression, loss of self-control, and bizarre thinking) on immediate memory. A hypothesized model, in which psychological disturbances indirectly impacted immediate memory via attention, was tested using structural equations modeling (EQS). The participants included heterogeneous groups of brain-damaged and psychiatric subjects both with and without age-corrected observed variables. These groups did not vary with regard to the relationships within the model, and all models had good fit indices [comparative fit index (CFI)>0.98]. Competing models with paths directly from psychological disturbances to verbal, spatial, and general immediate memory were not significant, and these competing models did not result in a better fitting model. Therefore, the best fitting, most parsimonious model was the hypothesized one. These results corroborate the hypothesis of an indirect relationship between psychological disturbances and immediate memory via attention.

Journal Article↗
PubMed2000

Regulation of sensitivity to 5-hydroxytryptamine in pulmonary supernumerary but not conventional arteries by a 5-HT(1D)-like receptor.

Bovine pulmonary supernumerary arteries are more sensitive to 5-hydroxtryptamine (5-HT) (pD(2) 6.43+/-0.25) than conventional arteries (pD(2) 5.32+/-0.16). This study investigated receptors for 5-HT in ring segments of these arteries. The 5-HT(2) receptor agonist, 2,5 dimethoxy-4-iodoamphetamine hydrobromide (DOI) constricts both arteries. The selective 5-HT(2) receptor antagonist ritanserin produced insurmountable antagonism of 5-HT concentration-response curves in both arteries, whereas the 5-HT(1B/1D) receptor antagonist N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'(5-methyl- 1,2,4-oxadiazol-3-yl[1,1,-biphenyl]-4-carboxamide hydrochloride (GR127935) produced much greater antagonism in supernumerary arteries. In rings preconstricted with 9,11-dideoxy-9, 11-methanoepoxy prostalagdin F(2alpha) (U46619) and relaxed with the adenylyl cyclase activator forskolin, the selective 5-HT(ID) receptor agonist 2-[5-[3-(4-methylsulphonylamino) benzyl-1,2, 4-oxadiazol-5-yl]-1H-indole-3-yl] ethylamine (L694247) reversed the relaxation. Concentration-response curves for L694247-induced reversal of forskolin-relaxation were antagonised by GR127935 in supernumerary (pK(B) 8.6) and conventional (pK(B) 8.4) arteries, whereas concentration-response curves to 5-HT-were less sensitive to antagonism by GR127935T and this was more obvious in conventional (pK(B) 7.6) than supernumerary (pK(B) 8.1) arteries. Neither the selective 5-HT(1D) receptor antagonist (1-(3-chlorophenyl)-4-[3, 3-diphenyl (2-(S,R) hydroxypropanyl)piperazine] hydrochloride (BRL15572) nor the 5-HT(1B) receptor antagonist (2,3,6, 7-tetrahydro-1'-methyl-5-[2'methyl-4'5-(methyl-1,2,4-oxadiazol-3-y l) biphenyl-4-carbonyl]furo[2,3-f]indole-3-spiro-4'-piperidine hydrochloride (SB224289) antagonised concentration-response curves induced by 5-HT or 5-HT(1)-receptor-selective agonists. In addition to the 5-HT(2A) receptor, 5-HT activates a GR127935-sensitive and a GR127935-insensitive receptor in these arteries. Supernumerary arteries have a greater proportion of GR127935-sensitive receptors, which display only some of the pharmacological characteristics of the cloned 5-HT(ID) receptor. It is possible that the GR127935-sensitive receptor could be a species homologue of the human 5-HT(1B) receptor that is insensitive to SB224289.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Sequence-dependent bending of DNA induced by cisplatin: NMR structures of an A.T-rich 14-mer duplex.

The NMR solution structure of the A.T rich DNA 14-mer duplex d(ATACATGGTACATA).d(TATGTACCATGTAT) is reported. This is compared with the NMR structure of the same duplex intrastrand cross-linked at the d(G*pG*) site by cis-(Pt(NH3)2¿2+, derived from the anticancer drug cisplatin. The unmodified duplex has B-DNA geometry, but there is a large positive base-pair roll (roll angle 24 +/- 2 degrees) at the T9-A10 step on the 3' side of the central GG site. Platination of the DNA duplex causes the adjacent guanine bases to roll toward one another (roll angle 44 +/- 4 degrees), leading to an overall helix bend of 52 +/- 9 degrees. The platinum atom is displaced from the planes of the coordinated G7* and G8* by 0.8 A and 0.3 A, respectively. The minor groove opposite the platinum lesion is widened and flattened, with geometric parameters similar to those of A-form DNA. The unwinding of the helix at the platination site is 26 degrees. Platination causes the DNA duplex to bend toward the 3'-end (with respect to the G*G* strand), in contrast to G C-rich structures reported previously, which bend toward the 5'-end. This difference can be attributed to the predisposition of the A.T rich duplex toward bending in this region. Protein recognition of bent platinated G*G* lesions may therefore exhibit a strong dependence on the local DNA structure.

Base Sequence↗
PubMed2000

Mode of action and application of Scorpion primers to mutation detection.

Scorpion primers can be used to detect PCR products in homogeneous solution. Their structure promotes a unimolecular probing mechanism. We compare their performance with that of the same probe sequence forced to act in a bimolecular manner. The data suggest that Scorpions indeed probe by a unimolecular mechanism which is faster and more efficient than the bimolecular mechanism. This mechanism is not dependent on enzymatic cleavage of the probe. A direct comparison between Scorpions, TaqMan and Molecular Beacons on a Roche LightCycler indicates that Scorpions perform better, particularly under fast cycling conditions. Development of a cystic fibrosis mutation detection assay shows that Scorpion primers are selective enough to detect single base mutations and give good sensitivity in all cases. Simultaneous detection of both normal and mutant alleles in a single reaction is possible by combining two Scorpions in a multiplex reaction. Such favourable properties of Scorpion primers should make the technology ideal in numerous applications.

Alleles↗
PubMed2000

Developmental apraxia arising from neonatal brachial plexus palsy.

OBJECTIVE: To determine whether motor unit activation is impaired in patients with persisting disability arising from neonatal brachial plexus palsy (NBPP). BACKGROUND: In NBPP patients, the authors previously found more extensive muscle reinnervation than might have been anticipated from the clinical examination. METHODS: Motor skills were tested in a group of nine boys and seven girls with prior NBPP, who then underwent physiologic investigation of proximal and distal muscles in their affected and unaffected arms. The latter tests comprised measurements of maximal evoked muscle compound action potential (M-wave) amplitude, maximal voluntary torque, twitch torque, and twitch interpolation. A group of 17 children of similar ages served as control subjects. RESULTS: In the NBPP group, motor skills were diminished and voluntary torque was reduced relative to M-wave amplitude and twitch torque. Moreover, interpolated twitches could be demonstrated in some NBPP patients but not in control subjects. CONCLUSION: Persisting disability in NBPP patients is due, at least in part, to impaired motor unit activation. The authors suggest that the impairment is a form of developmental apraxia caused by defective motor programming in early infancy.

Action Potentials↗
PubMed2000

Recognition of GT mismatches by Vsr mismatch endonuclease.

The Vsr mismatch endonuclease recognises the sequence CTWGG (W = A or T) in which the underlined thymine is paired with guanine and nicks the DNA backbone on the 5'-side of the mispaired thymine. By using base analogues of G and T we have explored the functional groups on the mismatch pair which are recognised by the enzyme. Removal of the thymine 5-methyl group causes a 60% reduction in activity, while removing the 2-amino group of guanine reduces cleavage by 90%. Placing 2-amino-purine or nebularine opposite T generates mis-matches which are cut at a much lower rate (0.1%). When either base is removed, generating a pseudoabasic site (1', 2'-dideoxyribose), the enzyme still produces site-specific cleavage, but at only 1% of the original rate. Although TT and CT mismatches at this position are cleaved at a low rate (approximately 1%), mismatches with other bases (such as GA and AC) and Watson-Crick base pairs are not cleaved by the enzyme. There is also no cleavage when the mismatched T is replaced with difluorotoluene.

2-Aminopurine↗
PubMed2000

Cyclic CD8+ lymphopenia in dogs experimentally infected with Bartonella vinsonii subsp. berkhoffii.

Until recently, it was presumed that Bartonella vinsonii only infected voles, a species of North American rodents. In April of 1993, however, our laboratory isolated a novel subspecies of B. vinsonii (B. vinsonii subsp. berkhoffii) from the blood of a dog diagnosed with vegetative valvular endocarditis. Subsequently, based on a seroepidemiologic survey of dogs from North Carolina and Virginia presenting for a variety of medical problems, we found evidence supporting a potentially important association between B. vinsonii and Ehrlichia canis co-infection in dogs. In the following study, eight dogs were infected with B. vinsonii: four specific pathogen free dogs and four dogs that had previously been infected with E. canis. Flow cytometric analysis of peripheral blood lymphocytes revealed a cyclic elevation of the CD4/CD8 T-cell ratio that correlated with cyclic CD8+ lymphopenia in all dogs infected with B. vinsonii, regardless of prior exposure to E. canis.

Animals↗
PubMed2000

Prospective trial of preoperative concomitant boost radiotherapy with continuous infusion 5-fluorouracil for locally advanced rectal cancer.

RATIONALE: To evaluate the response to a concomitant boost given during standard chemoradiation for locally advanced rectal cancer. METHODS AND MATERIALS: Concomitant boost radiotherapy was administered preoperatively to 45 patients with locally advanced rectal cancer in a prospective trial. Treatment consisted of 45 Gy to the pelvis with 18 mV photons at 1.8 Gy/fraction using a 3-field belly board technique with continuous infusion 5FU chemotherapy (300mg/m(2)) 5 days per week. The boost was given during the last week of therapy with a 6-hour inter-fraction interval to the tumor plus a 2-3 cm margin. The boost dose equaled 7.5 Gy/5 fractions (1.5 Gy/fraction); a total dose of 52.5 Gy/5 weeks was given to the primary tumor. Pretreatment tumor stage, determined by endorectal ultrasound and CT scan, included 29 with T3N0 [64%], 11 T3N1, 1 T3Nx, 2 T4N0, 1 T4N3, and 1 with TxN1 disease. Mean distance from the anal verge was 5 cm (range 0-13 cm). Median age was 55 years (range 33-77 years). The population consisted of 34 males and 11 females. Median time of follow-up is 8 months (range 1-24 months). RESULTS: Sphincter preservation (SP) has been accomplished in 33 of 42 (79%) patients resected to date. Three patients did not undergo resection because of the development of metastatic disease in the interim between the completion of chemoradiation (CTX/XRT) and preoperative evaluation. The surgical procedures included proctectomy and coloanal anastomosis (n = 16), low anterior resection (n = 13), transanal resection (n = 4). Tumor down-staging was pathologically confirmed in 36 of the 42 (86%) resected patients, and 13 (31%) achieved a pathologic CR. Among the 28 tumors (67%) located <6 cm from the anal verge, SP was accomplished in 21 cases (75%). Although perioperative morbidity was higher, toxicity rates during CTX/XRT were comparable to that seen with conventional fractionation. Compared to our contemporary experience with conventional CTX/XRT (45Gy; 1.8 Gy per fraction), improvements were seen in SP (79% vs. 59%; p = 0.02), SP for tumors <6 cm from the anal verge (75% vs. 42%; p = 0.003), and down-staging (86% vs. 62%; p = 0.003). CONCLUSION: The SP rate with concomitant boost radiation has been highly favorable with rates of response which are higher than those previously reported for chemoradiation without administration of a boost. Further evaluation of this radiotherapeutic strategy appears warranted.

Adult↗
PubMed2000

Cloning of CCRL1, an orphan seven transmembrane receptor related to chemokine receptors, expressed abundantly in the heart.

In an attempt to identify novel chemokine receptor genes, cDNA expressed sequence tags (EST) were analyzed for a significant homology with mammalian chemokine receptors. The sequence from one of the selected EST clones was used to generate a full-length cDNA encoding a putative seven transmembrane receptor, CCRL1-CC chemokine receptor like 1. The full-length receptor encodes a polypeptide of 350 amino acids and has about 35% homology to the chemokine receptors CCR6 and CCR7. Northern blot analysis indicates predominant expression of about 5.0, 2.0 and 1.3kb mRNA forms in human heart tissue, while low-level expression of the 2.0 and 1.3kb forms was observed in lung, pancreas and spleen and in fetal tissues. In-situ hybridization confirmed the presence of CCRL1 mRNA in cardiac muscle cells. Similar to the chemokine receptor CCR6, CCRL1 maps to chromosome 6 and has one intron in the 5' untranslated region. Coupled transcription-translation of CCRL1 cDNA yielded a glycosylated polypeptide of about 45kDa.

Amino Acid Sequence↗
PubMed2000

The influence of pulsatile preservation on renal transplantation in the 1990s.

BACKGROUND: Unlike simple cold storage (CS), pulsatile machine preservation (MP) of kidneys for transplantation permits pharmacologic manipulation of the perfusate and aids in the pretransplant assessment of the kidney graft. These characteristics of MP may have importance in the era of increasing use of extended criteria donor kidneys. The overall aim of this article is to critically assess practices at our preservation unit with respect to graft function. Specific aims are to (1) compare the influence of MP versus CS on graft function, (2) determine which pretransplant variables have significance in pretransplant assessment, and (3) determine whether pharmacologic manipulation during MP is advantageous. METHODS: There were 650 consecutive kidneys preserved in our laboratory between January 1, 1993 and March 1, 999, by either MP or CS. All MP kidneys were preserved by continuous hypothermic pulsatile perfusion using Belzer-MPS or Belzer II solution. Perfusion parameters and electrolytes were measured serially during pulsatile perfusion. All CS kidneys were stored in University of Wisconsin solution. All kidneys obtained from donors exhibiting extended criteria features underwent pretransplant frozen section biopsies. Transmission electron microscopy (EM) was performed on a subset of kidneys undergoing pharmacologic manipulation. Four agents were assessed prospectively for their ability to influence MP characteristics when added to perfusate: PGE1, trifluoperazine, verapamil, and papaverine. RESULTS: MP was associated with improved immediate, 1-, and 2-year graft function and reduced length of initial hospital stay when compared with CS grafts. Changes in the machine perfusion variables flow and resistance, and the [Ca++] in perfusate, were significantly associated with delayed graft function (DGF) after the transplant. Biopsy information was not predictive of DGF. The addition of PGE1 to perfusate improved MP characteristics, reduced the release of [Ca++] into perfusate, and ameliorated mitochondrial ischemic injury in transmission EM images. Early graft function was improved in the presence of PGE1+MP, compared with function in the presence of other pharmacologic agents or CS alone. CONCLUSIONS: MP is associated with improved early and long term renal function. Moreover, PGE1 augments MP in improving graft function. The combination of MP+PGE1 may be important in optimizing the ability to use extended donor criteria kidneys and, thereby, improve the overall efficiency of cadaveric renal transplantation.

Adenosine↗
PubMed2000

Optimal light dose for interstitial photodynamic therapy in treatment for malignant brain tumors.

BACKGROUND AND OBJECTIVE: The primary goal was to determine the maximal tolerable light dose that can be administered to patients undergoing multifiber interstitial photodynamic therapy (PDT) of malignant brain tumors at a fixed dose of photosensitizer. STUDY DESIGN/MATERIALS AND METHODS: Eighteen patients (12 glioblastomas, 5 anaplastic astrocytoma, and 1 malignant ependymoma) were included in this study. The total light dose delivered to the tumor was divided into three groups of six patients each: 1,500-3,700 J, 3,700-4,400 J, and 4,400-5,900 J. RESULTS: Five patients (all glioblastomas) demonstrated postoperative permanent neurologic deficits. None of the patients in 1,500-3,700 J, two patients in 3,700-4,400 J, and three patients in 4,400-5,900 J had neurologic deficits. Glioblastomas recurred more often than anaplastic astrocytomas. Increasing the light dose did not make a difference in local/regional control of glioblastomas. Patients with anaplastic astrocytomas survived (mean, 493 days) longer than patients with glioblastomas (mean, 116.5 days) after PDT. Four patients had prolonged survival (more than a year) after PDT. CONCLUSIONS: Increasing the total light dose delivered to the tumor increases the odds of having a permanent neurologic deficit but does not increase survival or time to tumor progression. There was no difference in local or marginal recurrence with increasing light dose. Recurrent anaplastic astrocytomas tend to do better than recurrent glioblastomas with PDT.

Adult↗
PubMed2000

The mapping from sound structure to the lexicon in aphasia: evidence from rhyme and repetition priming.

Two studies were conducted to explore the hypothesis that Broca's and Wernicke's aphasics have deficits arising from the processes involved in activating the lexicon from phonological form. The first study explored whether phonologically similar lexical entries differing only in their initial consonants show "rhyme priming." Results revealed that Broca's aphasics failed to show facilitation when the target was identical to the prime (i.e. identity priming) and they showed significant inhibition when targets were preceded by rhyming words. Wernicke's aphasics showed a pattern of results similar to that of normal subjects, i.e., identity priming and rhyme priming as well as significantly slower reaction-times in the rhyming condition compared to the identity condition. The second study investigated form-based repetition priming in aphasic patients at a number of intervals including when no other stimuli intervened between repeated stimuli (0 lag) or when 4, 8, or 12 stimuli intervened. Results showed that, unlike old normal subjects who showed repetition priming for both words and nonwords, both Broca's and Wernicke's aphasics showed repetition priming for word targets only. Moreover, in contrast to old normal subjects who showed a greater magnitude of priming at 0 lag for word targets, neither Broca's aphasics or Wernicke's aphasics showed priming at 0 lag. Implications of these findings are considered with respect to the hypotheses that Broca's and Wernicke's aphasics have deficits in the nature of the activation patterns within the lexicon itself and in auditory (working) memory.

Aged↗
PubMed2000

Revealing the existence of child abuse in the context of marital breakdown and custody and access disputes.

OBJECTIVE: Child abuse in the context of legal and de facto marital breakdown has received little attention internationally. Many believe it does not exist in this context and regard it as just a "gambit in the divorce wars." Recently, however, family courts in a number of countries have become concerned over the management of child abuse allegations in custody and access cases, known more commonly now as residence and contact cases. This article presents a unique research study, which investigated how the Family Court of Australia dealt with such cases. The study, covering all forms of child abuse, sought to discover who were the families bringing these problems to family courts, what precisely the abuse was and how the courts dealt with it. METHOD: The study reviewed court records of some 200 families where child abuse allegations had been made in custody and access disputes in jurisdictions in two states, observed court proceedings and interviewed court and related services' staff. RESULTS: The findings showed that these cases had become a core component of the court's workload without any public or professional awareness of this change, that the abuse was real, that it was severe and serious, and that the courts and child protection services did not provide appropriate services to the families. CONCLUSION: A new specialized intervention system was developed based on the research and it is now being trialed and evaluated. The new intervention system contains features derived from the research findings that may be suitable internationally for implementation.

Adult↗