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T Cook

Publications and source records attributed to T Cook.

At least 37 records · Page 2Linked to original sources
PubMed2001

Photoreceptor subtype specification: from flies to humans.

Multiple cell types often differentiate from a pluripotent cell. These cells may then further diversify as distinct subtypes. The visual system provides an ideal model for studying subtype specification as various photoreceptors acquire different functions based on the type of opsin they express. Opsin expression is mostly controlled through transcriptional mechanisms that are evolutionary conserved from Drosophila to humans. In addition, it appears that, from a "default" developmental state, distinct "acquired" photoreceptor states develop upon receiving intrinsic or extrinsic signals. This review discusses factors involved in opsin gene regulation and how their integration may explain how subtype specificity is achieved.

Animals↗
PubMed2001

Primary and secondary transconjunctival involutional entropion repair.

PURPOSE: Lower eyelid involutional entropion is a significant disorder of the aging population resulting from horizontal eyelid laxity, overriding orbicularis oculi muscle, and attenuation of the lower eyelid retractors. The purpose of this study is to describe the long-term results of transconjunctival entropion repair. DESIGN: Interventional noncomparative case series. PARTICIPANTS: Thirty-six eyelids in 31 patients. METHODS: Charts were reviewed of all transconjunctival entropion repairs, which included myectomy, retractor fixation, and horizontal shortening performed by three oculoplastic surgeons between January 1993 and January 1999. Cases with less than 12 months follow-up were excluded. MAIN OUTCOME MEASURES: Entropion recurrence. RESULTS: Thirty-six lids in 31 patients were followed for mean of 31.5 months (12.5-79). Six of 36 lids (16.7%) had postoperative complications. Recurrent entropion occurred in 3 of 36 lids (8.3%) an average 16.3 months (7-35) after surgery. An average of 6 trichiasis lashes (1-10) occurred in 4 of 36 lids (11.1%) at a mean of 2.25 months (1-4) after surgery. There were no overcorrections. Three of 36 lids (8.3%) required additional surgery. CONCLUSIONS: Entropion recurrence after three-step transconjunctival repair is within the 0% to 30% reported recurrence for other repair techniques but more frequent than reported for a similar transcutaneous procedure. The 8.3% recurrence rate might have resulted from inadequate myectomy, inadequate retractor fixation, cicatricial changes directly related to the transconjunctival incision, or progressive involutional changes. Trichiasis was the most frequent complication. Transconjunctival entropion repair may be slightly less effective than transcutaneous repair.

Aged↗
PubMed2001

Suggested specifications for a standardized Addiction Severity Index database.

The Addiction Severity Index (ASI) has become one of the most widely used instruments in the addictions field. As a result of its wide popularity, there are multiple versions of the instrument in use, and a wide range of computer systems used to collect and/or store ASI data. Thus, it has been difficult for different users and systems to share ASI data. This difficulty significantly reduces the value of the information for treatment providers, policy makers, and researchers. This article provides operational definitions and specifications for a "Standard ASI Database." Descriptions for standard variable names, data types, field lengths, value labels, range checks, and programming notes for all items in the fifth edition of the ASI are available electronically from the senior. Examples from the full protocol and the rationale for producing the Standard ASI Database elements are illustrated here. It is hoped that the format suggested will become the "industry standard" for ASI data storage among all users of the ASI and that, regardless of the software used or the method of data collection, there will be a single, standard format for all ASI databases. The potential applications from such a database would benefit treatment providers/clinicians and researchers as well as payers and policy makers.

Databases as Topic↗
PubMed2001

The flexiblade 2.

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Equipment Design↗
PubMed2001

Risk factors for a major coronary event after myocardial infarction in the Scandinavian Simvastatin Survival Study (4S). Impact of predicted risk on the benefit of cholesterol-lowering treatment.

AIMS: To analyse (1) the prognostic importance of clinical findings and lipids in patients with a previous myocardial infarction and (2) the relative and absolute benefit of simvastatin in patients at low, medium and high predicted risk. METHODS: The 4S was a double-blind, randomized, clinical trial of long-term treatment with simvastatin or matching placebo in patients with myocardial infarction or angina pectoris, serum total cholesterol 5.5-8.0 mmol x l(-1), and serum triglycerides <or=2.5 mmol x l(-1). The present study only deals with those 3525 patients who had a previous myocardial infarction. End-points comprised coronary death, definite and probable hospital verified myocardial infarction, and resuscitated cardiac arrest. Because there were few women the primary analyses were performed among men. RESULTS: A Cox model analysis in the placebo group identified the following independent predictors of coronary events: a history of hypertension (P=0.023), diabetes (P=0.0001), smoking after the myocardial infarction (P=0.010), total cholesterol (P=0.020), and HDL cholesterol (P=0.062). The relative reduction of risk by simvastatin treatment in patients at low, medium and high predicted risk was 38%, 39% and 42%, respectively, but the corresponding absolute benefit per 100 patients treated for 6 years increased from 7.9 to 16.2. CONCLUSION: In addition to serum lipids, clinical variables contributed significantly to prediction. The relative benefit from simvastatin treatment was independent of predicted risk, but the absolute benefit increased from low to high risk.

Anticholesteremic Agents↗
PubMed2001

Monitoring a clinical trial conducted under the Food and Drug Administration regulations allowing a waiver of prospective informed consent: the diaspirin cross-linked hemoglobin traumatic hemorrhagic shock efficacy trial.

In 1996, the US Food and Drug Administration (FDA) enacted Rule 21 CFR section 50.24, which allows a narrow exception to the requirement for prospective informed consent from human research subjects in clinical trials investigating potentially beneficial therapies for acute, life-threatening conditions. The first clinical trial to be conducted under this rule was sponsored by Baxter Healthcare Corporation and approved by the FDA on November 21, 1996. This large, multicenter, randomized clinical trial was designed to compare the addition of diaspirin cross-linked hemoglobin (DCLHb) with standard care in the initial resuscitation of adults experiencing severe, uncompensated, traumatic hemorrhagic shock. Before the first planned interim analysis of the data, review of fatal adverse events revealed an imbalance in mortality between the 2 treatment groups. The Data Monitoring Committee (DMC) recommended suspension of patient enrollment 24 days later. Additional data collection and analyses confirmed the excess number of deaths in patients treated with DCLHb but failed to reveal the cause of these deaths. The trial was formally terminated after only 112 of the planned 850 patients had been enrolled. We review the events leading up to and the rationale behind the DMC recommendations for suspension of patient enrollment and trial termination. Although the DCLHb trial was unsuccessful in achieving its goals, the monitoring process worked well. Emergency research was facilitated by DMC oversight, and the interests of research subjects were protected by the actions of the DMC.

Aspirin↗
PubMed2001

Why is there so much end-stage renal failure of undetermined cause in UK Indo-Asians?

There is a high incidence of end-stage renal failure (ESRF) of undetermined cause in the Indo-Asian population of the UK. We studied patients presenting from the district of Brent and Harrow, which has a large Indo-Asian community, and whose renal services are largely provided by our centre. The diagnosis and ethnicity of patients starting renal replacement therapy and/or undergoing renal biopsy were collated. The incidences of ESRF, rates of renal biopsy and underlying diagnoses were calculated for Indo-Asians and Caucasians. Requirement for renal replacement therapy in Indo-Asians presenting to our centre from Brent and Harrow was 221/10(6)/year; no underlying diagnosis was identified in 77/10(6)/year. Renal biopsy rate in these patients was 456/10(6)/year, and the diagnostic categories significantly over-represented compared to Caucasians were: hypertension and ischaemia, focal segmental glomerulosclerosis (FSGS), idiopathic interstitial nephritis (IIN), diabetic nephropathy, minor glomerular abnormality, lupus nephritis and non-specific advanced chronic renal disease (p<0.001). The first three of these had a combined incidence of 135/10(6)/year in Indo-Asians and 31/10(6)/year in Caucasians. ESRF of undetermined cause is common in UK Indo-Asians, as is requirement for renal biopsy. Hypertension with ischaemia, FSGS and IIN are over-represented in the Indo-Asian population, and should be targeted for early diagnosis and treatment in this group.

Adult↗
PubMed2001

Civilization as a threat to human health?

Civilization can be defined as the distinctly human attributes and attainments of a particular society. In general, the development of civilization is viewed as a positive step for the well-being of the human species, leading to an increased duration and quality of human life. The accelerated progress of civilization (mainly industrialization, urbanization and nutrition) has lead to new possibilities for adverse effects on human health. A collection of problems referred to as 'civilization diseases' has become the subject of serious concern but review of available data indicates that this concept appears to add very little to our understanding of modern environmental influences on human health. Important limitations in the continued use of this term are its non-specificity, the lack of a unifying scientific foundation, and provision of virtually no direction for remediation of these diseases or for future research. In addition, the use of this term has been localized to primarily post-socialist European countries. In view of these limitations, it seems more productive for scientists, in all parts of the world, to embrace the discipline of environmental health science and to discontinue use of the term "civilization diseases".

Civilization↗
PubMed2001

Musculoskeletal disorders among construction apprentices in Hungary.

The purpose of this study was to determine the prevalence of occupationally related musculoskeletal disorder (MSD) symptoms and carpal tunnel syndrome (CTS) among construction apprentices in Hungary. Symptoms of occupational MSDs and the job factors contributing to the symptoms were determined through an administered symptom and job factors survey. The prevalence of CTS was based on a case definition that included hand symptoms and nerve conduction studies of the median nerve across the carpal tunnel. The participation rate was 96% among the 201 eligible construction apprentices. More than 50% of the apprentices reported occupationally related musculoskeletal symptoms in the previous 12 months. Job tasks that required awkward postures and working in a static position were the two factors that contributed most to MSD symptoms. No cases of CTS were found in this sample of apprentices. Although disorders of the musculoskeletal system are more prevalent among experienced construction workers, this study indicated that symptoms of MSDs are present among young construction workers. Assessing the magnitude and nature of occupational related MSDs is the first step in promoting a healthier, safer, and more efficient workforce.

Carpal Tunnel Syndrome↗
PubMed2000

Expression of the cyclin-dependent kinase inhibitor p27 in keratoacanthoma.

BACKGROUND: Keratoacanthomas are characterized by initial rapid enlargement followed by clinical regression. A series of cyclin and cyclin-dependent kinase complexes regulate cell cycle progression. p27(kip) inhibits a variety of cyclin-cyclin-dependent kinase complexes in vitro and may act to hold eukaryotic cells in a quiescent state (G0). OBJECTIVE: We examined expanding and regressing keratoacanthomas for expression of p27(kip). METHODS: An immunohistochemical method was used to visualize and count p27(kip)-labeled cells in 5 expanding and 15 regressing keratoacanthomas. RESULTS: In normal epidermis p27(kip) was found overlying the nuclei of suprabasilar keratinocytes. In expanding keratoacanthoma there was little expression of p27(kip) in nuclei of atypical keratinocytes composing the tumor (1.25 +/- 2.1 labeled cells per high-power field); in regressing keratoacanthoma the nuclei of most suprabasilar keratinocytes in atypical tumor aggregates contained p27(kip) (55.1 +/- 28.6 labeled cells per high-power field). The difference was significant at P values of less than.001. CONCLUSION: The identification of p27(kip) in regressing keratoacanthoma but not in expanding keratoacanthoma suggests that p27(kip) may be playing a role in promoting regression of keratoacanthoma and is a potential target for pharmacologic intervention.

Cell Cycle Proteins↗
PubMed2000

Pharmacokinetics of orally administered camptothecins.

Phase I trials of oral camptothecins, including camptothecin (CPT) and irinotecan (CPT-11), have reported substantial interpatient variability in systemic exposure, which could result in suboptimal antitumor activity in some patients or enhanced risk for toxicity in others. This investigation evaluates the contribution of intestinal absorption and first-pass metabolism in the disposition of oral CPT and CPT-11, respectively. The transport of CPT in Caco-2 cell lines (validated model of intestinal drug transport) was concentration dependent and saturable (Vmax: 34 x 10(-5) cm/sec and Km: 20 microM), and was temperature dependent with an activation energy (Ea) of 11.7 kcal/mole. Cumulatively, this data was indicative of carrier-mediated intestinal transport. In addition, a reduction of transport in the presence of sodium azide plus deoxyglucose suggested ATP dependence. Thus, variable expression and availability of intestinal transporters could contribute to the observed wide variability in the exposure to oral CPT. CPT-11 is hydrolyzed by the ubiquitous enzyme carboxyl esterase to active SN-38, and first-pass metabolism of oral CPT-11 would include both intestinal and hepatic hydrolysis. Incubation of CPT-11 with S9 fractions of human liver and intestinal tissues resulted in variable rates of formation of SN-38. The mean (+/- SD) specific activities (pmoles/min/mg) were: liver (8.57 +/- 10.4, n = 8), duodenum (5.06 +/- 3.7, n = 4), jejunum (6.44 +/- 2.8, n = 5), ileum (4.81 +/- 2.4, n = 5), colon (1.93 +/- 1.5, n = 6), and rectum (0.82, n = 1). Interestingly, there was a decrease in SN-38 formation by tumor tissue compared to matched normal liver and colon tissues. Therefore variable first-pass metabolism could contribute to the substantial differences in the systemic exposures to CPT-11 and SN-38 in patients receiving oral CPT-11.

Administration, Oral↗
PubMed2000

Tetanus.

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Adolescent↗
PubMed2000

TIEG proteins join the Smads as TGF-beta-regulated transcription factors that control pancreatic cell growth.

The control of epithelial cell proliferation, differentiation, and apoptosis requires a balance between signaling and transcriptional regulation. Recent developments in pancreatic cell research have revealed that transforming growth factor-beta (TGF-beta) signaling is important for the regulation of each of these phenomena. More importantly, perturbations in this pathway are associated with pancreatic cancer. A chief example of these alterations is the mutation in the TGF-beta-regulated transcription factor Smad4/DPC4 that is found in a large percentage of pancreatic tumors. Surprisingly, studies on transcription factors have remained an underrepresented area of pancreatic research. However, the discovery of Smad4/DPC4 as a transcription factor fueled further studies aimed at characterizing transcription factors involved in normal and neoplastic pancreatic cell growth. Our laboratory recently described the existence of a novel family of zinc finger transcription factors, TGF-beta-inducible early-response gene (TIEG)1 and TIEG2, from the exocrine pancreas that, similarly to Smads, participate in the TGF-beta response and inhibit epithelial cell proliferation. This review therefore focuses on describing the structure and function of these two families of transcription factor proteins that are becoming key players in the regulation of pancreatic cell growth.

Animals↗
PubMed2000

Development of GnRH antagonists for prostate cancer: new approaches to treatment.

Prostate cancer has become the most common cancer among American men and is second only to lung cancer as a cause of male cancer-related death. Several treatment options exist for different stages of prostate cancer including observation, prostatectomy, radiation therapy, chemotherapy, and hormone therapy. Hormone therapy has evolved from the use of estrogens to gonadotropin-releasing hormone (GnRH) agonists and recently, investigational GnRH antagonists. GnRH receptor agonists such as leuprolide, bruserelin and goserelin have been used for the treatment of prostate cancer. These agonists eventually cause the inhibition of lutenizing hormone production, which in turn causes a suppression of testosterone and dihydrotestosterone, on which continued growth of prostate cancer cells depend. Several comparative studies of leuprorelin administered as daily injections or monthly depot injections have been reported. Disease progression was prevented in more than 72% of men administered daily leuprorelin, and in 82% to 89% of those receiving monthly depots. Another synthetic GnRH analog, goserelin, has been studied in a similar population of men with daily injections producing partial responses in 60% to 80% of men with previously untreated prostate cancer. Abarelix, a peptide antagonist of GnRH receptor, is also being studied for the treatment of prostate cancer. The discovery and development of GnRH antagonists may provide an important advance for patients with prostate cancer. Clearly the studies described herein, as well as many others, outline an exciting era of research to define the optimal use of hormonal therapy in prostate cancer.

Antineoplastic Agents, Hormonal↗
PubMed1999

Three conserved transcriptional repressor domains are a defining feature of the TIEG subfamily of Sp1-like zinc finger proteins.

Sp1-like transcription factors are characterized by three highly homologous C-terminal zinc finger motifs that bind GC-rich sequences. These proteins behave as either activators or repressors and have begun to be classified into different subfamilies based upon the presence of conserved motifs outside the zinc finger domain. This classification predicts that different Sp1-like subfamilies share certain functional properties. TIEG1 and TIEG2 constitute a new subfamily of transforming growth factor-beta-inducible Sp1-like proteins whose zinc finger motifs also bind GC-rich sequences. However, regions outside of the DNA-binding domain that differ in structure from other Sp1-like family members remain poorly characterized. Here, we have used extensive mutagenesis and GAL4-based transcriptional assays to identify three repression domains within TIEG1 and TIEG2 that we call R1, R2, and R3. R1 is 10 amino acids, R2 is 12 amino acids, and R3 is approximately 80 amino acids long. None of these domains share homology with previously described transcriptional regulatory motifs, but they share strong sequence homology and are functionally conserved between TIEG1 and TIEG2. Together, these data demonstrate that TIEG proteins are capable of repressing transcription, define domains critical for this function, and further support the idea that different subfamilies of Sp1-like proteins have evolved to mediate distinct transcriptional functions.

Amino Acid Sequence↗