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T King

Publications and source records attributed to T King.

At least 55 records · Page 3Linked to original sources
PubMed1998

The role of the brachyury gene in heart development and left-right specification in the mouse.

The midline has a theoretical role in the development of left-right asymmetry, and this is supported by both genetic analyses and experimental manipulation of midline structures in vertebrates. The mouse brachyury (T) gene encodes a transcription factor which is expressed in the developing notochord and is required for its development. T/T mice lack a mature notochord and have a dorsalised neural tube. We have examined the hearts of T/T mice and have found consistent morphological abnormalities, resulting in ventrally displaced ventricular loops, and a 50% incidence of inverted heart situs. Three TGF-beta related genes, lefty-1, lefty-2 and nodal, are expressed asymmetrically in mouse embryos, and are implicated in the development of situs. We find that nodal, which is normally expressed around the node and in left lateral plate mesoderm in early somite embryos, is completely absent at this stage in T/T embryos. In contrast, lefty-1 and lefty-2, which are normally expressed in the left half of prospective floorplate and left lateral plate mesoderm, respectively, are both expressed in T/T embryos only in a broad patch of ventral cells in, and just rostral to, the node region. These results implicate the node as a source of instructive signals driving expression of nodal and lefty-2 in the left lateral plate mesoderm, and being required for normal looping and situs of the heart.

Animals↗
PubMed1998

Nursing strategies to prevent ventilator-associated pneumonia.

Critically ill patients who require mechanical ventilation are at high risk for development of pneumonia during the course of treatment. Ventilator-associated pneumonia leads to higher rates of mortality and morbidity, increased length of hospital stay, and higher hospital costs. The intubation that is necessary for mechanical ventilation impairs the patient's normal defense mechanisms for fighting infection. Impaired defenses, along with such risk factors as age of the patient, equipment used, and failure of the staff to wash hands increase the likelihood of colonization of the lower airways. Colonization and subsequent pneumonia commonly occurs from microaspiration of secretions from the oropharynx and gastrointestinal tract. In this article, the mechanism of microaspiration, diagnosis of ventilator-associated pneumonia, and nursing strategies to reduce the incidence of pneumonia are described.

Adult↗
PubMed1997

Embryonic asymmetry: left TGFbeta at the right time?

Vertebrates have consistent differences between their left and right sides. In all species, nodal, a transforming growth factor beta superfamily signalling protein, is involved in a late step in the pathways that specify such asymmetry in the embryo. Earlier components seem not so well conserved.

Animals↗
PubMed1997

Sex differences in visual recognition memory: support for a sex-related difference in attention in adults and children.

The selectivity hypothesis of Meyers-Levy (1989) proposes that cognitive sex differences reflect underlying differences in information processing between males and females. Males are considered to be more likely to organize information in a self-related manner, whereas females are more likely to adopt a comprehensive approach to information processing. We tested this hypothesis in children (10-15 years) and adults using recognition memory tasks. Tests were devised which employed male-oriented objects, female oriented objects, or random objects. In both the child and adult samples, females performed significantly better than males on tests using random and female-oriented objects. Males performed at the level of females only when tested for recognition of male-oriented objects. These results demonstrate that this sex difference is present prior to puberty and support the concept of sex differences in information processing.

Adolescent↗
PubMed1997

11BetaOH-progesterone affects vascular glucocorticoid metabolism and contractile response.

Vascular smooth muscle (VSM) contains a bidirectional isoform of 11beta-hydroxysteroid dehydrogenase (11beta-HSD), the enzyme that can metabolize endogenous glucocorticoids to their respective 11-dehydro derivatives. 11BetaOH-progesterone (11betaOH-P), a compound that can be produced in vivo, is as potent or more potent than licorice derivatives in inhibiting renal and hepatic 11beta-HSD. When studied in homogenates prepared from primary cultures of rat VSM, 11betaOH-P and its derivative, 11-keto-progesterone (11-keto-P), proved to be potent, directionally specific inhibitors of vascular 11beta-HSD. 11BetaOH-P selectively inhibited the forward dehydrogenase reaction (corticosterone-->11-dehydrocorticosterone), whereas 11-keto-P selectively blocked the reverse oxidoreductase reaction. To test the physiological effects, vascular rings were prepared from rat aorta. Rings were incubated in culture media containing either a submaximal concentration of corticosterone (10 nmol/L), 11-dehydrocorticosterone (100 nmol/L), 11betaOH-P (1 micromol/L), 11-keto-P (1 micromol/L), or a combination of glucocorticoid and inhibitor for 24 hours. After the 24-hour incubation, rings were briefly stimulated sequentially with phenylephrine (10 nmol/L to 1 micromol/L) and angiotensin II (1 micromol/L). The immediate contractile response in rings incubated with both corticosterone and 11betaOH-P was greater than in rings previously incubated with either the corticosterone or 11betaOH-P alone (eg, response to 100 nmol/L phenylephrine in milligrams of force, mean+/-SE: corticosterone, 728+/-56, n=9; 11betaOH-P, 325+/-105, n=4; both, 1132+/-122, n=8; corticosterone versus both, P<.01). In contrast, the immediate contractile responses to phenylephrine and to angiotensin II were attenuated in rings exposed previously to both 11-dehydrocorticosterone and 11-keto-P. Thus, 11betaOH-P and 11-keto-P (and possibly structurally similar compounds) alter the vascular effects of glucocorticoids and may play a role in glucocorticoid-induced hypertension.

Animals↗
PubMed1997

Influence of dietary sodium on the renal isoforms of 11 beta-hydroxysteroid dehydrogenase.

Endogenous glucocorticoids are converted to their biologically inert 11-dehydroderivatives by isoforms of the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). The low-K(m), NAD(+)-dependent renal isoform (Type 2) identified in the distal nephron protects mineralocorticoid receptors from activation by endogenous glucocorticoids. The function of high-K(m), NADP(+)-dependent renal isoform (Type 1) is less well understood. Since glucocorticoids may modulate sodium transport in renal proximal tubules (PT), we hypothesized that Type 1 activity in this segment may be regulated by dietary Na(+)-11 beta-HSD activity was assessed in homogenates of canine PT by the conversion of cortisol to cortisone in the presence of NADP+ 200 microM. A high-Na+ diet for 4 days increased the Vmax 4-fold, with no change in the Type 1 K(m) (40 mEq/day Na+ diet: K(m) 0.959 microM, Vmax 3.40 pmoles/min/mg protein versus 150 mEq/day Na+ diet: K(m) 0.962 microM, Vmax 14.8 pmoles/min/mg protein). Type 1 mRNA also rose in the salt repleted animals. The high-Na+ diet produced no detectable change in the Type 2 isoform enzyme kinetics and mRNA level. No reverse oxo-reductase activity was noted with either renal isoform. Thus, renal Type 1 11 beta-HSD can be regulated by dietary Na+ independent of changes in the renal Type 2 isoform.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Environmental contamination due to methicillin-resistant Staphylococcus aureus: possible infection control implications.

OBJECTIVE: To study the possible role of contaminated environmental surfaces as a reservoir of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals. DESIGN: A prospective culture survey of inanimate objects in the rooms of patients with MRSA. SETTING: A 200-bed university-affiliated teaching hospital. PATIENTS: Thirty-eight consecutive patients colonized or infected with MRSA. Patients represented endemic MRSA cases. RESULTS: Ninety-six (27%) of 350 surfaces sampled in the rooms of affected patients were contaminated with MRSA. When patients had MRSA in a wound or urine, 36% of surfaces were contaminated. In contrast, when MRSA was isolated from other body sites, only 6% of surfaces were contaminated (odds ratio, 8.8; 95% confidence interval, 3.7-25.5; P < .0001). Environmental contamination occurred in the rooms of 73% of infected patients and 69% of colonized patients. Frequently contaminated objects included the floor, bed linens, the patient's gown, overbed tables, and blood pressure cuffs. Sixty-five percent of nurses who had performed morning patient-care activities on patients with MRSA in a wound or urine contaminated their nursing uniforms or gowns with MRSA. Forty-two percent of personnel who had no direct contact with such patients, but had touched contaminated surfaces, contaminated their gloves with MRSA. CONCLUSIONS: We concluded that inanimate surfaces near affected patients commonly become contaminated with MRSA and that the frequency of contamination is affected by the body site at which patients are colonized or infected. That personnel may contaminate their gloves (or possibly their hands) by touching such surfaces suggests that contaminated environmental surfaces may serve as a reservoir of MRSA in hospitals.

Bacterial Typing Techniques↗
PubMed1996

p53 mutations do not predict response to paclitaxel/radiation for nonsmall cell lung carcinoma.

BACKGROUND: Mutations in the tumor suppressor gene p53 have been associated with resistance to ionizing radiation and chemotherapy. Paclitaxel and concurrent radiation (paclitaxel/RT) achieve high response rates with locally advanced nonsmall cell lung carcinoma (NSCLC). In vitro data and animal studies suggest that paclitaxel may have a unique ability to activate tumor cell apoptosis in the absence of wild-type p53 function. The authors sought to determine whether p53 mutations affect response to paclitaxel/RT in patients with locally advanced NSCLC. METHODS: Thirty patients with Stage IIIA or IIIB NSCLC who participated in Brown University Oncology Group protocols utilizing paclitaxel/RT had tumor tissue that was adequate for analysis. Mutations were detected in tumor tissue by single-strand conformation polymorphism analysis of exons 5 through 8 of the p53 gene, and confirmed by direct sequencing. RESULTS: Mutations in p53 were found in 12 of 30 patients (40%). The response rates (complete plus partial) of 75% for patients with tumors with p53 mutations, and 83% for patients with wild-type p53, did not differ significantly (P = 0.70). CONCLUSIONS: p53 mutations do not predict response of patients with NSCLC to paclitaxel/RT. This finding is in striking contrast to results with other chemotherapeutic agents and ionizing radiation. These clinical data support in vitro data and animal studies regarding the unique mechanism of the action of paclitaxel. Further investigation is needed to determine the mechanism of lung tumor cell death after paclitaxel/RT. These results suggest that paclitaxel/RT may be an active regimen for patients with other locally advanced neoplasms with high rates of p53 gene mutations.

Aged↗
PubMed1996

Comparison of symptoms after the consumption of milk or lactose-hydrolysed milk by people with self-reported severe lactose intolerance.

BACKGROUND: Ingestion of a large dose of the milk sugar lactose--for example, the 50 g load in 1 liter of milk--causes symptoms such as abdominal pain, diarrhoea, bloating and flatulence in the majority of people with lactose malabsorption. It is uncertain whether the ingestion of more common doses of lactose, such as the amount in 240 mol (8 oz) of milk, causes symptoms. Some people insist that even smaller quantities of milk, such as the amount used with cereal or coffee, cause severe gastrointestinal distress. METHODS: In a randomized, double-blind, cross-over trial, we evaluated gastrointestinal symptoms in 30 people (mean age, 29.4 years; range 18-50) who reported severe lactose intolerance after ingesting less than 240 ml of milk. The ability to digest lactose was assessed by the subjects' end-alveolar hydrogen concentration after they ingested 15 g of lactose in 250 ml of water. Subjects then received either 240 ml of lactose-hydrolysed milk containing 2% fat or 240 ml of milk containing 2% fat and sweetened with aspartame to approximate the taste of the lactose-hydrolysed milk; each type of milk was administered daily with breakfast for a 1-week period. Using a standardized scale, subjects rated the occurrence and severity of bloating, abdominal pain, diarrhoea, and flatus and recorded each passage of flatus. RESULTS: Twenty-one participants were classified as having lactose malabsorption and nine as being able to absorb lactose. During the study periods, gastrointestinal symptoms were minimal (mean symptom-severity scores for bloating, abdominal pain, diarrhoea, and flatus between 0.1 and 1.2 [1 indicated trivial symptoms, 2 indicated mild symptoms]). When the periods were compared, there were no statistically significant differences in the severity of these four gastrointestinal symptoms. For the lactose malabsorption group, the mean (+/- SEM) difference in episodes of flatus per day was 2.5 +/- 1.1 (95% confidence interval, 0.2-4.8). Daily dietary records indicated a high degree of compliance, with no additional sources of lactose reported. CONCLUSIONS: People who identify themselves as severely lactose-intolerant may mistakenly attribute a variety of abdominal symptoms to lactose intolerance. When lactose intolerance is limited to the equivalent of 240 ml of milk or less a day, symptoms are likely to be negligible and the use of lactose digestive aids unnecessary.

Journal Article↗
PubMed1996

Psychometric scores and persistence of irritable bowel after infectious diarrhoea.

BACKGROUND: Although previous studies have shown that psychological disturbances are frequently associated with the irritable bowel syndrome (IBS), the relation was not necessarily cause and effect. The development of chronic bowel symptoms after an episode of acute gastroenteritis has allowed us to examine prospectively the role of psychological factors. METHODS: Seventy-five patients with acute gastroenteritis completed a series of psychometric tests soon after admission to hospital. Of these, 22 had persistent symptoms compatible with IBS after the acute illness, and in 20 of these the symptoms were still present at six months. FINDINGS: At the time of their initial illness, patients who subsequently developed IBS had higher scores for anxiety, depression, somatization and neurotic trait than those who returned to normal bowel function. The psychometric scores had not changed when remeasured after the acute illness. Lactose malabsorption was not an important factor. INTERPRETATION: These results support the hypothesis that psychological factors are important in IBS.

Journal Article↗
PubMed1996

Interferon alfa for macular degeneration.

Clinical studies demonstrate that interferon alfa has little benefit in treating CNV secondary to macular degeneration. However, it may be useful in the treatment of choroidal and retinal hemangiomas, diabetic and post-vein occlusion retinopathy, and retinopathy of prematurity.

Antineoplastic Agents↗
PubMed1995

The embryo's one-sided genes.

The origin of left-right asymmetry during vertebrate embryogenesis has long been a puzzle; now, for the first time, genes have been identified that are expressed with left-right asymmetric patterns in early embryos.

Journal Article↗
PubMed1995

Transcervical quinacrine sterilization: clinical experience.

OBJECTIVE: To review the use of quinacrine pellets for non-surgical female sterilization. BACKGROUND: The transcervical insertion of quinacrine pellets has been under study for over 15 years. It could potentially expand access to sterilization services, because it is relatively simple to administer, with the use of a modified IUD inserter, and is inexpensive. METHODS: Published and unpublished data are reviewed. RESULTS: The short-term safety of transcervical quinacrine appears to be better than surgical sterilization, but it is less effective, especially among women under 35, and there are virtually no data on its reversibility. Thus, it is probably most appropriate for older women, aged 35 and over, but it could be an option for others where access to surgical sterilization is limited. CONCLUSION: The use of quinacrine pellets for female sterilization needs to be reviewed by appropriate regulatory authorities, especially with regard to long-term safety issues, and additional clinical studies are needed to better define a standardized regimen.

Cervix Uteri↗
PubMed1995

Bidirectional activity of 11 beta-hydroxysteroid dehydrogenase in vascular smooth muscle cells.

Endogenous glucocorticoids (GC) can be metabolized through the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD); in the rat, corticosterone (B) is converted to its inactive metabolite 11-dehydrocorticosterone (A). Since increased tissue concentrations of GCs may affect blood pressure by potentiating the vasoactive effects of alpha-adrenergic agonists and possibly other pressors, we studied the metabolism of corticosterone in freshly dissected aortae and cultured vascular smooth muscle cells (VSMC). Incubations were generally conducted for 60 min with 10(-8) M steroid; steroids were isolated and identified by HPLC. In aortic minces stripped of endothelium, the oxo-reductase reaction of A back to B was nearly 4 times greater than the dehydrogenase reaction of B to A (2.8 +/- 0.5 x 10(-11) versus 7.3 +/- 1.0 x 10(-12) mol/mg protein). This pattern was also seen in cultured VSMC during growth and quiescent states (growth A to B 3.2 +/- 0.4 x 10(-12) versus B to A 9.7 +/- 0.9 x 10(-13) mol/mg protein; quiescent A to B 8.8 +/- 0.1 x 10(-12) versus B to A 1.2 +/- 0.2 x 10(-12) mol/mg protein). Enzyme activity in either direction was less during growth, correlating with a decrease in mRNA for 11 beta-OHSD. In cell homogenates containing 200 microM NADP(H), the enzyme functioned equally in either direction at pH 7.4 with an apparent Km for corticosterone of approximately 2 x 10(-7) M. Carbenoxolone, an inhibitor of 11 beta-OHSD, suppressed the dehydrogenase reaction to a greater degree than the reverse oxo-reductase reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Meta-analysis of enteral nutrition as a primary treatment of active Crohn's disease. Gastroenterology 1995; 108:1056-67.

UNLABELLED: The efficacy of enteral nutrition as primary therapy of active Crohn's disease is controversial. The aim of the study was to compare by meta-analysis the likelihood of clinical response to liquid diet therapy vs. corticosteroids and to assess the importance of formula composition to efficacy. METHODS: Randomised controlled trials comparing exclusive enteral nutrition with corticosteroids and elemental with non-elemental formulas were identified through a combination of computerised and hand-searching techniques. Rates of clinical remission of active Crohn's disease, based on the intention to treat principle, were extracted from the studies by two independent reviewers. Odds ratios for the likelihood of clinical response were calculated. RESULTS: In eight trials comprising 413 patients, enteral nutrition was inferior to corticosteroids (pooled odds ratio 0.35; 95% confidence interval 0.23-0.53). In five trials comprising 134 patients, there was no difference in the efficacy of elemental versus non-elemental formulas (pooled odds ratio 0.87; 95% confidence interval 0.41-1.83). CONCLUSIONS: Corticosteroids are more effective than enteral nutrition in the treatment of active Crohn's disease. Limited sample size precludes definite conclusions about the importance of formula composition in the efficacy of enteral nutrition; however, data analysed in this study do not support an advantage to elemental feedings compared with a polymeric formulation.

Journal Article↗