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Biomedical subjects

T Williams

Publications and source records attributed to T Williams.

At least 19 recordsLinked to original sources
PubMed1992

Characterization of phycocyanin produced by cpcE and cpcF mutants and identification of an intergenic suppressor of the defect in bilin attachment.

Mutants of the cyanobacterium Synechococcus sp. PCC 7002 constructed by the insertional inactivation of either the cpcE or cpcF gene produce low levels of spectroscopically detectable phycocyanin. The majority of the phycocyanin produced in these strains appears to lack the alpha subunit phycocyanobilin (PCB) chromophore (Zhou, J., Gasparich, G. E., Stirewalt, V. L., de Lorimier, R., and Bryant, D. A. (1992) J. Biol. Chem. 267, 16138-16145). Purification of the phycocyanin produced in the mutants revealed two fractions each with an aberrant absorption spectrum. Tryptic peptide maps of the major fraction showed that the alpha-84 PCB peptide was absent. The two PCB peptides derived from the beta subunit were normal. Tryptic digests of the less abundant phycocyanin fraction contained a family of bilin peptides derived from the alpha subunit. Several distinct bilin adducts were present. A major component was a mesobiliverdin adduct, a previously described product of the in vitro reaction of PCB and apophycocyanin. The same results were obtained with both the cpcE mutant and the cpcF mutant. In vitro reactions with PCB and the fractions containing apo alpha subunit showed that the alpha-84 bilin attachment site was unmodified and competent for adduct formation. Pseudo-revertants of both strains were observed to arise at high frequency. Analysis of the phycocyanin from a cpcE pseudo-revertant, which produced a near wild-type level of phycocyanin with alpha subunit carrying PCB, revealed a single amino acid substitution, alpha-Tyr129----Cys. This residue, which is conserved in all phycocyanins sequenced to date, forms part of the alpha-84 bilin binding site and lies within 5 A of alpha-Cys84. A mutated cpcA gene containing this substitution was constructed by site-directed mutagenesis and transformed, along with cpcB, into a cpcBAC deletion strain containing an insertionally inactivated cpcE. This strain produces high levels of phycocyanin and the majority of the alpha subunit carries PCB at alpha-Cys84.

Amino Acid Sequence↗
PubMed1992

Comparison of laparoscopic cholecystectomy versus elective open cholecystectomy.

Laparoscopic cholecystectomy has essentially replaced open cholecystectomy as the procedure of choice for gallbladder disease. This rapid shift to laparoscopic cholecystectomy, however, has resulted more from marketing forces than from prospective clinical trials. To evaluate the safety and efficacy of laparoscopic cholecystectomy, the first 486 laparoscopic cholecystectomies at two institutions were studied. These results were then compared to the results of the last 6 months of elective open cholecystectomy cases prior to the introduction of laparoscopic surgery. The age, sex, height, and weight were similar in both groups. The mean operative time was 78.8 +/- 1.8 min for laparoscopic cholecystectomy and 62.7 +/- 2.6 min for open cholecystectomy (p < 0.01). The mean time for tolerating a regular diet was 1.23 +/- 0.04 days in the laparoscopic group versus 2.44 +/- 0.07 days in the open group (p < 0.01). Laparoscopic cholecystectomy patients required only oral pain medications by a mean of 1.22 +/- 0.03 days postoperatively compared to 2.55 +/- 0.07 days postoperatively for those undergoing open cholecystectomy (p < 0.01). The mean length of hospitalization was 1.58 +/- 0.07 days for laparoscopic patients and 3.55 +/- 0.11 days for open patients (p < 0.01). Thirty-one patients undergoing laparoscopic cholecystectomy were converted to open cholecystectomy (6.4%). The most common reasons for conversion to open cholecystectomy were acute inflammation, adhesions, and bleeding. For the laparoscopic patients, the morbidity rate was 8.4% and the mortality rate 0.2% (1 death). In the open cholecystectomy group the morbidity rate was 8.0% and there were no deaths. The most troublesome complication in laparoscopic cholecystectomies continues to be bile leaks and bile duct injuries.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1992

Saliva activated transmission (SAT) of Thogoto virus: relationship with vector potential of different haematophagous arthropods.

Tick saliva (or salivary gland extract) potentiates the transmission of Thogoto (THO) virus to uninfected ticks feeding on a non-viraemic guinea-pig. This phenomenon has been named saliva activated transmission (SAT). To investigate the potential of different haematophagous arthropods to mediate SAT, guinea-pigs were infested with uninfected R.appendiculatus Neumann nymphs and inoculated with THO virus and salivary gland extract (SGE) derived from a range of ixodid (metastriate and prostriate) or argasid ticks, or mosquitoes; control guinea-pigs were inoculated with virus alone. Enhancement of THO virus transmission was observed only when SGE was derived from metastriate ticks. Comparison with the vector potential of these various arthropod species revealed that enhancement of THO virus transmission was specific for ticks which were competent vectors of the virus. The data indicate a correlation between vector competence and the ability of haematophagous arthropods to mediate SAT of THO virus.

Aedes↗
PubMed1992

The core promoter region of the tumor necrosis factor alpha gene confers phorbol ester responsiveness to upstream transcriptional activators.

Activators of protein kinase C, such as 12-O-tetradecanoylphorbol 13-acetate (TPA), are known to regulate the expression of many genes, including the tumor necrosis factor alpha (TNF) gene, by affecting the level or activity of upstream transcription factors. To investigate the mechanism whereby TPA activates the TNF promoter, a series of 5'-deletion mutants of the human TNF promoter linked to chloramphenicol acetyltransferase was transfected into U937 human promonocytic cells. TPA produced a 7- to 11-fold activation of all TNF promoters tested, even those promoters truncated to contain only the core promoter with no upstream enhancer elements. The proximal TNF promoter containing only 28 nucleotides upstream and 10 nucleotides downstream of the RNA start site confers TPA activation to a variety of unrelated upstream enhancer elements and transcription factors, including Sp1, CTF/NF1, cyclic AMP-response element, GAL-E1a, and GAL-VP16. The level of activation by TPA depends on the TATA box structure, since the TPA response is greater in promoters containing the sequence TATAAA than in those containing TATTAA or TATTTA. These findings suggest that the core promoter region is a target for gene regulation by second-messenger pathways.

Base Sequence↗
PubMed1992

99mTechnetium-labelled red blood cell scintigraphy as an alternative to angiography in the investigation of gastrointestinal bleeding: clinical experience in a district general hospital.

99mTechnetium-labelled red blood cell scintigraphy (99mTc RBC scintigraphy) was used as the second-line investigation to localise bleeding in 23 patients (11 male, 12 female; mean age 67 years) presenting with active bleeding per rectum. Scintigraphy was available on a 24 h basis. A total of 18 patients had positive scans (78%). Surgery was performed urgently in 11 patients and the site of bleeding, as predicted by scintigraphy, was confirmed in 9 (82%). 99mTc RBC scintigraphy was less useful in patients who were not bleeding actively or who were being investigated for chronic anaemia. This study suggests that 99mTc RBC scintigraphy can play a useful role in the preoperative localisation of unexplained gastrointestinal bleeding in hospitals with nuclear medicine facilities, but confirms it has little place in the management of patients unless they are bleeding actively.

Adult↗
PubMed1992

The surgical significance of Persian Gulf sand.

Foreign bodies, in particular sand and soil particles, can cause considerable reaction in wounds and remain in tissues indefinitely. The introduction of foreign material as a contaminant in wounds and intracavitary injuries to military personnel deployed in the Persian Gulf region can be a complicating factor in treatment. Samples of desert sand from the military operational areas of the Persian Gulf were analyzed and the acute local and systemic responses of intraperitoneal contamination determined in an experimental rat model.

Animals↗
PubMed1992

Cardiopulmonary transplantation service establishment in the 1990s: Australia--a developing country?

1. A National Transplantation Service has been established at the Alfred Hospital performing more than 50 transplants per year. 2. Increased access to transplantation technology has facilitated an improvement in national population servicing from 2.7 to 6.2 transplants per million population per year. National funding of A$4.062 million per year has been secured. 3. Basic research into organ preservation has facilitated transcontinental organ procurement. 4. An active lung transplantation program has been established synchronous with the cardiac transplant service activities. 5. MCS program establishment has paralleled clinical transplantation activities. 6. Budget management and cost containment has been achieved through rationalisation of management protocols.

Australia↗
PubMed1991

Sequence specific protein binding to and activation of the TGF-beta 3 promoter through a repeated TCCC motif.

We have previously characterized the TGF-beta 3 promoter and shown that the activity of this promoter is highly variable in different cell types. Although the promoter contains a proximal cAMP responsive element, which is critical to basal and forskolin-induced promoter activity, this element is not responsible for the variable, cell-specific regulation of the promoter. In this paper, we identify a 25 base pair sequence in the proximal region of the TGF-beta 3 promoter that binds a novel DNA-binding protein. This region includes the sequence T-CCCTCCCTCCC, (3 x TCCC), and mutation of these T-CCC repeats inhibits protein binding. Further, we show that in the cell line A375, which we have previously shown expresses high levels of TGF-beta 3 mRNA, this region is responsible for mediating high level TGF-beta 3 promoter activity. Immediately 3' to the 3 x TCCC sequence is a consensus AP-2 binding site, however, we show that this region does not bind AP-2, and AP-2 does not transactivate the TGF-beta 3 promoter. Therefore, we provide strong evidence that high level expression of TGF-beta 3 in A375 cells results from transactivation of the TGF-beta 3 promoter by a protein that binds to a repeated TCCC motif in the promoter and suggest that this DNA-binding protein likely also regulates aspects of developmental and tissue-specific expression of this cytokine.

Animals↗
PubMed1991

Characterization of a dimerization motif in AP-2 and its function in heterologous DNA-binding proteins.

The mammalian transcription factor AP-2 is a retinoic acid inducible sequence-specific DNA-binding protein that is developmentally regulated. In this report, the functional domains necessary for AP-2 DNA binding were studied. AP-2 required a dimerization domain and an adjacent region of net basic charge to achieve a sequence-specific protein:DNA interaction. The sequences responsible for dimerization consisted of two putative amphipathic alpha helices separated by a large intervening span region. This helix-span-helix (HSH) domain was unable to bind DNA when separated from the basic region, but was still capable of dimerization. The ability of the HSH domain to function as a module that promotes DNA binding through dimerization was further demonstrated by attaching it to the heterologous basic region of the c-Jun proto-oncogene product. The resulting chimeric protein specifically recognized an AP-1 DNA-binding site in the absence of an intact c-Jun leucine repeat and in a manner that was dependent on the presence of a functional AP-2 dimerization domain.

Adenosine Triphosphate↗
PubMed1991

Bacterial resistances to mercury and copper.

Heavy metals are toxic to living organisms. Some have no known beneficial biological function, while others have essential roles in physiological reactions. Mechanisms which deal with heavy metal stress must protect against the deleterious effects of heavy metals, yet avoid depleting the cell of a heavy metal which is also an essential nutrient. We describe the mechanisms of resistance in Escherichia coli to two different heavy metals, mercury and copper. Resistance of E. coli to mercury is reasonably well understood and is known to occur by transport of mercuric ions into the cytoplasmic compartment of the bacterial cell and subsequent reductive detoxification of mercuric ions. Recent mutational analysis has started to uncover the mechanistic detail of the mercuric ion transport processes, and has shown the essential nature of cysteine residues in transport of Hg(II). Resistance to copper is much less well understood, but is known to involve the increased export of copper from the bacterial cell and modification of the copper; the details of the process are still being elucidated. Expression of both metal resistance determinants is regulated by the corresponding cation. In each case the response enables the maintenance of cellular homeostasis for the metal. The conclusions drawn allow us to make testable predictions about the regulation of expression of resistance to other heavy metals.

Amino Acid Sequence↗
PubMed1991

Self-report measures of obsessionality, depression and social anxiety in a school population of adolescents.

The results are reported for a non-clinical school population of 252 adolescent subjects, aged 13 to 15 years, responding to the Maudsley Obsessive-Compulsive Inventory (MOCI), the Children's Depression Inventory (CDI) and the List of Social Situation Problems (LSSP). The scales intercorrelated significantly but appear to measure different aspects of self perception. No significant age or gender effects emerged in any. The results obtained are compared with those of previous studies and the use of the MOCI in adolescent populations discussed.

Adolescent↗
PubMed1991

Determining cancer-patient-management educational needs.

The authors have proposed a model for curriculum planning and continuing medical education (CME) program development (JCE 4:255-259, 1989.) This paper reports the results of an application of this model. The knowledge examination administered was developed by specialists and family practice physicians, covering four cancer sites and eight cancer-patient management stages. The purpose of this application was to evaluate the model regarding its effectiveness in terms of whether specific core competencies could be identified as the basis for curriculum planning and/or CME program-planning use. It was assumed that data from this assessment could be extrapolated from the residency context to the development of CME programs. A total of 200 respondent reports (interns, residents, faculty) from 15 institutions (medical schools or hospitals) were analyzed. In general, more education improves test scores; faculty (6.5% of the respondents) averaged about 66% correct answers. The highest percentage of correct responses was associated with the site Breast (60%) and the stage Shared Care (70%). The lowest percentage of correct values was associated with the site Colorectal (45%) and the stage Treatment (44%). The pair Colorectal/Treatment produced the lowest percentage of correct answers observed (27%). The proactive model applied in this study was successful regarding determination of core-competency deficiencies. Participant responses were useful for identifying cancer-patient-management core-competency deficiencies, knowledge gaps that could be used for both curriculum planning and CME program development. Residency directors from participating institutions have reported using this information to modify the educational experience of individual residents as well as to modify their cancer program curriculum.(ABSTRACT TRUNCATED AT 250 WORDS)

Curriculum↗
PubMed1991

Risks and benefits of laparoscopic cholecystectomy in the community hospital setting.

Laparoscopic cholecystectomy has rapidly become more popular than open cholecystectomy. To further evaluate the safety and efficacy of laparoscopic cholecystectomy in the community setting, the first 190 patients to undergo the procedure in Saginaw, Michigan were studied. There were 159 females and 31 males. The mean age was 47.8 years. All patients had symptoms consistent with biliary tract disease and most had gallstones proven by preoperative ultrasound. The mean operative time was 84 minutes but decreased from 161 minutes the first month of the study to 74 minutes by the seventh month. Eighty-seven percent of patients were tolerating a regular diet by postoperative day 1. Ninety-six percent of patients were requiring only oral pain medications by postoperative day 1. Seventy percent of patients were discharged by postoperative day one while 91% were discharged by postoperative day 2. Six patients were converted to open cholecystectomy due to acute inflammation, significant bleeding or extensive adhesions. There were no deaths and the morbidity rate was 9.5%. The most significant complication was postoperative bile leak which occurred in two patients. Patients returned to work a mean of 16.1 days following surgery and to their normal daily activities at home a mean of 12.9 days postoperatively. This study of the first 190 laparoscopic cholecystectomies in Saginaw affirms the safety and feasibility of this procedure in the community setting in selected patients.

Biliary Tract Diseases↗
PubMed1991

Effect of acupuncture-point stimulation on diastolic blood pressure in hypertensive subjects: a preliminary study.

Electrical stimulation of four specific acupuncture points (Liver 3, Stomach 36, Large Intestine 11, and the Groove for Lowering Blood Pressure) was examined in order to determine the effect of this stimulation on diastolic blood pressure in 10 subjects with diastolic hypertension. Subjects were randomly divided into two groups: (1) an Acu-ES group, which received electrical stimulation applied to the four antihypertensive acupuncture points, and (2) a Sham-ES group, which received electrical stimulation applied to non-acupuncture-point areas. A repeated-measures analysis of variance revealed a significant, immediate poststimulation reduction of diastolic blood pressure for the Acu-Es group versus the Sham-ES group. Further studies are needed to determine whether there are other acupuncture points, stimulation characteristics, or modalities that can enhance this treatment effect and whether the treatment effect can last for a clinically significant period of time.

Acupuncture Points↗