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Biomedical subjects

T Harris

Publications and source records attributed to T Harris.

At least 19 recordsLinked to original sources
PubMed2001

Comparison of a virtual microscope laboratory to a regular microscope laboratory for teaching histology.

Emerging technology now exists to digitize a gigabyte of information from a glass slide, save it in a highly compressed file format, and deliver it over the web. By accessing these images with a standard web browser and viewer plug-in, a computer can emulate a real microscope and glass slide. Using this new technology, the immediate aims of our project were to digitize the glass slides from urinary tract, male genital, and endocrine units and implement them in the Spring 2000 Histology course at the University of Iowa, and to carry out a formative evaluation of the virtual slides of these three units in a side-by-side comparison with the regular microscope laboratory. The methods and results of this paper will describe the technology employed to create the virtual slides, and the formative evaluation carried out in the course. Anat Rec (New Anat) 265:10-14, 2001.

Computer-Assisted Instruction↗
PubMed2001

High plasma insulin and lipids profile in older individuals: the Italian longitudinal study on aging.

BACKGROUND: The inverse relationship of insulin level to high-density lipoprotein (HDL)-cholesterol and its positive association with hypertriglyceridemia has been demonstrated in several studies; however, the relationship of insulin to low-density lipoprotein (LDL)-cholesterol in elderly persons is not clear. This study investigates the relationships of fasting plasma insulin and selected metabolic and biological risk factors in an aged population. METHODS: The present study is based on a cross-sectional analysis of the data collected at baseline of the Italian Longitudinal Study on Aging in 1992 on a random sample of 5632 Italians aged 65-84 years. Analyses were performed to compare the distribution of risk factors, such as blood level of lipids, creatinine, albumin, fibrinogen, apolipoprotein A-1 and B, blood pressure, and body mass index (BMI), by quartiles of insulin, in both diabetic and nondiabetic participants. RESULTS: Significantly higher levels of triglycerides and BMI and lower levels of HDL-cholesterol were found in the upper quartile of insulin among nondiabetic individuals. In men, we also found significantly higher levels of systolic and diastolic blood pressure. The same trend for these variables, although not significant for HDL-cholesterol and blood pressure, was seen in diabetic men. In diabetic women, total and LDL-cholesterol were significantly lower in the highest insulin quartile (p <.001), while no significant differences were seen in nondiabetic women or in men. We also found higher levels of white blood cells in the highest insulin quartile of diabetic women. CONCLUSIONS: These results, apparently in disagreement with earlier reports on the clustering of cardiovascular disease risk factors in hyperinsulinemic individuals, could be due to the high frequency of chronic inflammation and the high prevalence of urinary infections in older diabetic women.

Aged↗
PubMed2001

Ketamine sedation for pediatric gastroenterology procedures.

BACKGROUND: Although the dissociative sedative ketamine is used commonly for pediatric procedural sedation in other settings, the safety of this agent in pediatric gastroenterology is not well-studied. A 5-year experience with ketamine sedation for pediatric gastroenterology procedures was reviewed to document the safety profile of this agent and to identify predictors of laryngospasm during esophagogastroduodenoscopy (EGD). METHODS: The study was a retrospective consecutive case series of children receiving ketamine administered by pediatric gastroenterologists skilled in basic airway management to facilitate pediatric gastrointestinal procedures during a 5-year period. Patient's records were reviewed to determine indication, dosage, adverse effects, drugs, inadequate sedation, and recovery time for each sedation. A multiple logistic regression analysis was performed to identify predictors of laryngospasm during EGD. Outcome measures were descriptive features of sedation, including adverse effects and predictors of laryngospasm during EGD. RESULTS: During the study period pediatric gastroenterologists administered ketamine 636 times, primarily for EGD (86%) and primarily by the intravenous route (98%). The median loading dose and total dose were 1.00 mg/kg and 1.34 mg/kg, respectively. Inadequate sedation was noted in seven (1.1%) procedures. Adverse effects included transient laryngospasm (8.2%), emesis (4.1%), recovery agitation (2.4%), partial airway obstruction (1.3%), apnea and respiratory depression (0.5%), and excessive salivation (0.3%). There were no adverse outcomes attributable to ketamine. Nearly half (46%) the subjects had severe underlying illness (American Society of Anesthesiologists (ASA] class > or =3). All instances of laryngospasm occurred during EGD (9.5% incidence), and the only independent predictor of laryngospasm in this sample was decreasing age. The incidence of laryngospasm was 13.9% in preschool-aged (< or =6 years) children and was 3.6% in school-aged (>6 years) children (difference 10.3%, 95% confidence intervals 5.5-14.9%). No dose relationship was noted with laryngospasm, and the risk did not increase with underlying illness. CONCLUSION: Pediatric gastroenterologists skilled in ketamine administration and basic airway management can effectively administer this drug to facilitate gastrointestinal procedures. Transient laryngospasm occurred in 9.5% of children receiving ketamine for EGD, and its incidence was greater in preschool than in school-aged children.

Adolescent↗
PubMed2000

State scholarship, loan forgiveness, and related programs: the unheralded safety net.

CONTEXT: In the mid-1980s, states expanded their initiatives of scholarships, loan repayment programs, and similar incentives to recruit primary care practitioners into underserved areas. With no national coordination or mandate to publicize these efforts, little is known about these state programs and their recent growth. OBJECTIVES: To identify and describe state programs that provide financial support to physicians and midlevel practitioners in exchange for a period of service in underserved areas, and to begin to assess the magnitude of the contributions of these programs to the US health care safety net. DESIGN: Cross-sectional, descriptive study of data collected by telephone, mail questionnaires, and through other available documents, (eg, program brochures, Web sites). SETTING AND PARTICIPANTS: All state programs operating in 1996 that provided financial support in exchange for service in defined underserved areas to student, resident, and practicing physicians; nurse practitioners; physician assistants; and nurse midwives. We excluded local community initiatives and programs that received federal support, including that from the National Health Service Corps. MAIN OUTCOME MEASURES: Number and types of state support-for-service programs in 1996; trends in program types and numbers since 1990; distribution of programs across states; numbers of participating physicians and other practitioners in 1996; numbers in state programs relative to federal programs; and basic features of state programs. RESULTS: In 1996, there were 82 eligible programs operating in 41 states, including 29 loan repayment programs, 29 scholarship programs, 11 loan programs, 8 direct financial incentive programs, and 5 resident support programs. Programs more than doubled in number between 1990 (n = 39) and 1996 (n = 82). In 1996, an estimated 1306 physicians and 370 midlevel practitioners were serving obligations to these state programs, a number comparable with those in federal programs. Common features of state programs were a mission to influence the distribution of the health care workforce within their states' borders, an emphasis on primary care, and reliance on annual state appropriations and other public funding mechanisms. CONCLUSIONS: In 1996, states fielded an obligated primary care workforce comparable in size to the better-known federal programs. These state programs constitute a major portion of the US health care safety net, and their activities should be monitored, coordinated, and evaluated. State programs should not be omitted from listings of safety-net initiatives or overlooked in future plans to further improve health care access. JAMA. 2000;284:2084-2092.

Cross-Sectional Studies↗
PubMed2000

General anesthetic action at an internal protein site involving the S4-S5 cytoplasmic loop of a neuronal K(+) channel.

The structural bases of general anesthetic action on a neuronal K(+) channel were investigated using the series of homologous 1-alkanols, electrophysiology, and mutational analysis. Domain swapping between dShaw2 (alkanol-sensitive) and hKv3.4 (alkanol-resistant) and site-directed mutagenesis demonstrated that a 13-amino acid cytoplasmic loop (S4-S5) determines the selective inhibition of native dShaw2 channels by 1-alkanols. The S4-S5 loop may contribute to a receptor for both 1-alkanols and the inactivation particle, because the enhanced 1-alkanol sensitivity of hKv3.4 channels hosting S4-S5 mutations correlates directly with disrupted channel inactivation. Evidence of a discrete protein site was also obtained from the analysis of the relationship between potency and alkyl chain length, which begins to level off after 1-hexanol. Rapid application to the cytoplasmic side of inside-out membrane patches shows that the interaction between dShaw2 channels and 1-alkanols equilibrates in <200 ms. By contrast, the equilibration time is >1000-fold slower when the drug is applied externally to outside-out membrane patches. The data strongly favor a mechanism of inhibition involving a discrete internal site for 1-alkanols in dShaw2 K(+) channels. A new working hypothesis proposes that 1-alkanols lock dShaw2 channels in their closed conformation by a direct interaction at a crevice formed by the S4-S5 loop.

1-Butanol↗
PubMed2000

Genetics, genomics, and drug discovery.

Genetics and genomics are altering the drug discovery process and changing the practice of medicine. Genetic mapping and positional cloning will lead to the identification of disease susceptibility alleles of different genes and this will be further enabled by the publication of the DNA sequence of the human genome. Single nucleotide polymorphisms discovered by comparative sequencing and other methods will also speed up positional cloning and allow pharmacogenetics to proceed in a more comprehensive way than heretofore. Gene expression arrays coupled with studies in model organisms will help to define the function of all genes and determine how the products interact-the next big step. High throughput protein structure determination will also provide large-scale descriptions of protein function but with more biochemical clarity. In all of these studies data integration remains the biggest challenge.

Drug Design↗
PubMed2000

An ERP investigation of binding and coreference.

This study examines the nature of violations in processing one class of binding construction, namely those involving reflexives and their antecedents. When arguments of verbs appear at the point where a syntactic violation is detected, a centroparietal positivity occurs, peaking at 600 ms after the presentation of the stimulus (P600), as is consistent with other types of syntactic anomalies. However, nonarguments in similar sentences fail to elicit the same response. For example, the reflexive in "John's brothers like himself" is in an argument position and elicits the P600 when compared to its grammatical counterpart. The nonargument, participating in the same type of mismatch, "John's brothers like Bill and himself," does not elicit the same positivity. This provides evidence that there are two processes involved in parsing this binding construction, one syntactic and another as yet unidentified, perhaps involving meaning or pragmatics.

Adolescent↗
PubMed2000

Finding function through structural genomics.

The recent availability of whole-genome sequences and large numbers of protein-coding regions from high-throughput cDNA analysis has fundamentally changed experimental biology. These efforts have provided huge databases of protein sequences, many of which are of unknown function. Deciphering the functions of these myriad proteins presents a major intellectual challenge.

Amino Acid Sequence↗
PubMed2000

Structural genomics in the biotechnology sector.

Commercial efforts in structural genomics focus on providing to pharmaceutical customers information that relates to the suitability of specific proteins as drug targets and the informed selection and refinement of lead compounds generated by high-throughput screening and rational approaches. These efforts follow a variety of business models and are impacted by activities in the public domain, recent technological advances, and the changing intellectual property landscape.

Animals↗
PubMed2000

The importance of ERK activity in the regulation of cyclin D1 levels and DNA synthesis in human cultured airway smooth muscle.

The relationship between persistent ERK (extracellular signal-regulated kinase) activity, cyclin D1 protein and mRNA levels and cell cycle progression in human cultured airway smooth muscle was examined in response to stimulation by ET-1 (endothelin-1), thrombin and bFGF (basic fibroblast growth factor). Thrombin (0.3 and 3 u ml(-1)) and bFGF (0.3 and 3 nM) increased ERK activity for more than 2 h and increased cell number, whereas ET-1 (100 nM) transiently stimulated ERK activity and was non-mitogenic. The MEK1 (mitogen-activated ERK kinase) inhibitor, PD 98059 (30 microM), inhibited both ERK phosphorylation and activity, and either prevented (thrombin 0.3 and 3 u ml(-1), bFGF 300 pM) or attenuated (bFGF 3 nM) DNA synthesis. Thrombin and bFGF increased both cyclin D1 mRNA and protein levels. PD 98059 decreased cyclin D1 protein levels stimulated by the lower but not higher thrombin concentrations. Moreover, increases in cyclin D1 mRNA levels were unaffected by PD 98059 pretreatment, irrespective of the mitogen or its concentration, suggesting that inhibition of cyclin D1 protein levels occurred by a post-transcriptional mechanism. These findings indicate that the control of cyclin D1 protein levels may occur independently of the MEK1/ERK signalling pathways. The inhibition of S phase entry by PD 98059 at higher thrombin concentrations appears to result from effects on pathways downstream or parallel to those regulating cyclin D1 protein levels. These findings suggest heterogeneity in the signalling of DNA synthesis in human cultured airway smooth muscle.

Bronchi↗
PubMed2000

Muscle strength and body mass index as long-term predictors of mortality in initially healthy men.

BACKGROUND: Muscle weakness, low body weight, and chronic diseases are often observed in the same people; however, the association of muscle strength with mortality, independent of disease status and body weight, has not been elucidated. The aim was to assess hand grip strength as a predictor of all-cause mortality within different levels of body mass index (BMI) in initially disease-free men. METHODS: Mortality was followed prospectively over 30 years. Maximal hand grip strength tests and BMI assessments were done at baseline in 1965 to 1970. The participants were 6040 healthy men aged 45 to 68 years at baseline living on Oahu, Hawaii. RESULTS: The death rates per 1000 person years were 24.6 in those with BMI <20, 18.5 in the middle BMI category, and 18.0 in those with BMI > or = 25. For grip strength tertiles, the mortality rates were 24.8 in the lowest, 18.5 in the middle, and 14.0 in the highest third. In Cox regression models, within each tertile of grip strength, BMI showed only minimal effect on mortality. In contrast, in each category of BMI there was a gradient of decreasing mortality risk with increasing grip strength. Among those with BMI <20, the adjusted relative risks (RRs) of mortality over 30 years were 1.36 (95% confidence interval 1.14-1.63) for those in the lowest third of strength at baseline, 1.27 (1.02-1.58) in the middle, and 0.92 (0.66-1.29) in the highest third. Correspondingly, for those with BMI 20-24.99, the RRs of death were 1.25 (1.08-1.45), 1.14 (1.00-1.32), and 1.0 (reference) in the lowest, middle, and highest third of grip strength, respectively. In those with BMI > or =25, the RRs were 1.39 (1.16-1.65) in the lowest, 1.27 (1.08-1.49) in the middle, and 1.14 (0.98-1.32) in the highest third of grip strength. Models were adjusted for age, education, occupation, smoking, physical activity, and body height. CONCLUSIONS: In healthy middle-aged men, long-term mortality risk was associated with grip strength at baseline, independent of BMI. The possible interpretation of the finding is that early life influences on muscle strength may have long-term implications for mortality. Additionally, higher strength itself may provide greater physiologic and functional reserve that protects against mortality.

Aged↗
PubMed2000

Four examples of anti-TSEN and three of TSEN-positive erythrocytes.

BACKGROUND: TSEN (MNS33) is a low-incidence antigen in the MNS blood group system encoded by hybrid glycophorin genes. TSEN is expressed by a unique amino acid sequence that results from the junction of GPA(58) to GPB(27), if the GPB carries S antigen. Until this study, only one example of anti-TSEN had been found. Antibody screening red blood cells (RBCs) positive for both S and s (ref. No. C873) reacted with four patient sera. Initially, the RBCs had been typed as S+s+, but later were typed as S-s+ in another laboratory. Two other RBC samples, one from a volunteer blood donor (D.L.), the other from a patient whose serum contained anti-En(a)FR (J.S.), also gave anomalous results when tested with anti-S. We suspected the presence of TSEN-positive hybrids on all three RBC samples. MATERIALS AND METHODS: Reactive sera (O.B., E.C., S.K., R.F.) were tested against RBCs with normal MNS phenotypes and with TSEN-positive RBCs. The RBCs of D.L., J.S. and C873 were tested with anti-S whose reactivity with S+s+ TSEN+ RBCs had been established previously, and with the original example of anti-TSEN. Immunoblotting was performed on the C873, D.L. and J.S. RBC membranes using a monoclonal antibody to an epitope common to both glycophorin A and glycophorin B. RESULTS: The sera from O.B., E.C., S.K. and R.F. were strongly reactive on the indirect antiglobulin test with TSEN+ RBCs. The RBCs of C873, D.L. and J.S. were typed as TSEN+. Immunoblotting pattern of D.L. and C873 were consistent with TSEN heterozygotes, while that of J.S. was consistent with a TSEN homozygote. CONCLUSIONS: Based on the estimated number of screening events with C873 RBCs, the incidence of anti-TSEN is approximately 1 in 20,000 sera. The antibody is found in patients with and without documented exposure to allogeneic RBCs. All known examples of anti-TSEN are IgG, but their clinical significance is not known.

Adult↗
PubMed2000

Cardiff depression study. A sib-pair study of life events and familiality in major depression.

BACKGROUND: An excess of both depression and undesirable life events in first-degree relatives of probands with depression as compared with controls has been reported. This association may have reflected a familial factor in common. AIMS: To examine the familiality of life events and depression and whether there may be a common familial factor influencing vulnerability to depression and the experiencing of life events. METHOD: In a sib-pair design, 108 probands with depression and their siblings were compared with 105 healthy controls and their siblings for psychopathology and life events. RESULTS: The lifetime relative risk of depressive disorder in the siblings of depressed subjects as compared with siblings of controls was 9.74, although these groups did not differ in the life events measures. Several categories of events showed significant sibling correlations, but this was due to the same event affecting both members of the pair. CONCLUSIONS: Although depressive disorder was strongly familial, the familial effects on life events were largely explained by shared experiences. There was no evidence for a common factor influencing both depression and life events.

Adolescent↗