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Biomedical subjects

T Holt

Publications and source records attributed to T Holt.

At least 19 recordsLinked to original sources
PubMed2006

Examination of potential methods to predict pulmonary arterial pressure score in yearling beef cattle.

Susceptibility of beef cattle to high altitude disease (HAD) is of major importance to economic and genetic selection on high elevation ranches. However, currently the best indicator of HAD susceptibility is the pulmonary arterial pressure (PAP) test, a test with high cost and invasive nature. Therefore, 2 experiments were undertaken to determine whether emerging technologies that predict blood components could be used to predict the PAP score in yearling Angus cattle. In Exp. 1, 39 yearling Angus bulls were used to determine if a relationship existed between PAP score and 10 blood components provided by a hemogram using whole blood or oxygen saturation as predicted by pulse oximetry in nonanesthetized cattle measured rectally or orally. Three of the hemogram values (packed cell volume, hemoglobin concentration, and red cell distribution width) were correlated (P < 0.10) with the PAP score. Prediction equations for PAP score were generated using the hemogram values and resulted in R2 values of 0.375 and 0.305 for the regression model using all of values and the best 2-variable model, respectively. Pulse oximetry was able to provide oxygen saturation predictions rectally or orally; however, the predicted values were not correlated with the PAP score (P > 0.10) or with each other (P > 0.10). In Exp. 2, 84 yearling Angus cattle (62 bulls, 22 heifers) were used to evaluate the ability of a portable clinical analyzer to predict the PAP score using 11 blood components from a sample of whole blood evaluated at the processing chute. The portable clinical analyzer was able to provide values for all of the 11 blood components; however, none of the predicted values were correlated with the PAP score (P > 0.10). In these preliminary experiments, 3 blood component values provided via the hemogram were the only variables both correlated with the PAP score and able to contribute to the development of a useful PAP prediction equation that could reduce the cost of traditional measures of HAD susceptibility. Future research is needed to determine whether additional blood components or emerging blood analysis technologies are able to accurately predict the PAP score in beef cattle.

Altitude Sickness↗
PubMed2005

Paying research participants: a study of current practices in Australia.

OBJECTIVE: To examine current research payment practices and to inform development of clearer guidelines for researchers and ethics committees. DESIGN: Exploratory email based questionnaire study of current research participant reimbursement practices. A diverse sample of organisations and individuals were targeted. SETTING: Australia. PARTICIPANTS: Contacts in 84 key research organisations and select electronic listservers across Australia. A total of 100 completed questionnaires were received with representations from a variety of research areas (for example, market, alcohol and drug, medical, pharmaceutical and social research). MAIN MEASUREMENTS: Open-ended and fixed alternative questions about type of research agency; type of research; type of population under study; whether payment is standard; amounts and mechanisms of payment; factors taken into account when deciding on payment practices; and whether payment policies exist. RESULTS: Reimbursement practice is highly variable. Where it occurs (most commonly for drug dependent rather than health professional or general population samples) it is largely monetary and is for time and out-of-pocket expenses. Ethics committees were reported to be often involved in decision making around reimbursement. CONCLUSIONS: Research subject payment practices vary in Australia. Researchers who do provide payments to research participants generally do so without written policy and procedures. Ethics committees have an important role in developing guidelines in this area. Specific guidelines are needed considering existing local policies and procedures; payment models and their application in diverse settings; case study examples of types and levels of reimbursement; applied definitions of incentive and inducement; and the rationale for diverse payment practices in different settings.

Australia↗
PubMed2001

Using an integrated measurement system as a common language: lessons from the U.S. Army medical department.

The Process of developing an integrated measurement system for the U.S. Army Medical Department (AMEDD) is examined in this study. A fundamental issue is whether the measures of performance accumulated by any information system are the correct ones and whether these measures appropriately reflect managers' decision making. Measurement is proposed as a solution to performance barriers. The four steps involved in building the AMEDD integrated measurement system (IMS) model are set out. Strategy is explored as the key input to the IMS model. An activity-based management (ABM) model that can support the required IMS cost-based measures is also described and the interrelationship between the two models is illustrated. The key test for application of the IMS model will be whether linking strategy and measurement results in information that improves decision making.

Benchmarking↗
PubMed2000

Analysis of latency in cattle after inoculation with a temperature sensitive mutant of bovine herpesvirus 1 (RLB106).

Calves were inoculated with the bovine herpes virus 1 (BHV-1) vaccine strain (RLB 106), which is a temperature sensitive mutant. The route of inoculation was intranasal instillation or intramuscular (i.m.) injection (flank or neck). As a control, five calves were given placebo by i.m. injection of the neck. Regardless of the infection route, clinical symptoms did not occur. However, BHV-1 neutralizing antibodies were detected after inoculation demonstrating that sero-conversion occurred. At 60 days post-inoculation, dexamethasone was given by i.m. injection to attempt reactivation of RLB 106. Only those calves inoculated by the intranasal route shed virus leading to an increase in BHV-1 specific antibodies. As expected, viral DNA and the latency related-RNA were detected in trigeminal ganglia (TG) of calves inoculated by the intranasal route. In contrast, viral nucleic acid was not detected in TG of calves inoculated by the i.m. route or in calves inoculated with placebo. In cervical ganglia or sacral dorsal root ganglia, viral nucleic acid was not consistently detected. This study provides evidence that efficient latency and reactivation does not occur following i.m. inoculation. Since serum-neutralizing antibodies were detected in all inoculated calves, i.m. inoculation led to sero-conversion.

Administration, Intranasal↗
PubMed2000

UK measles outbreak in non-immune anthroposophic communities: the implications for the elimination of measles from Europe.

We describe the epidemiology of the first nationwide outbreak of measles infection in the UK since the implementation of a mass vaccination campaign. Notifications of infectious diseases, interview and postal questionnaire identified 293 clinical cases, 138 of which were confirmed by salivary IgM, measles virus isolation and PCR. Twelve were epidemiologically linked to confirmed cases. The outbreak began in London, after contact with measles infection probably imported from Italy. Measles genotyping determined by sequence analysis confirmed spread to other unimmunized anthroposophic communities in the north, south west and south coast of England. Only two cases had been vaccinated against measles infection, and 90% of cases were aged under 15 years. Measles virus can selectively target non-immune groups in countries with high vaccine uptake and broader herd immunity. Without harmonization of vaccination policies and uniform high coverage across Europe, the importation and spread of measles virus amongst non-immune groups may prevent the elimination of measles.

Adolescent↗
PubMed1999

A Ras protein from a phytopathogenic fungus causes defects in hyphal growth polarity, and induces tumors in mice.

Ras is a low-molecular-weight guanine nucleotide (GDP/GTP)-binding protein that transduces signals for growth and differentiation in eukaryotes. In mammals, the importance of Ras in regulating growth is underscored by the observation that activating mutations in ras genes are found in many animal tumors. Colletorichum trifolii is a filamentous fungal pathogen of alfalfa which causes anthracnose disease. To investigate signaling pathways that regulate growth and development in this fungus, a gene encoding a Ras homolog (CT-Ras) was cloned from C. trifolii. CT-Ras exhibited extensive amino acid similarity to Ras proteins from higher and lower eukaryotes. A single amino acid change resulting in mutationally activated CT-Ras induced cellular transformation of mouse (NIH 3T3) fibroblasts and tumor formation in nu/nu mice. In Colletotrichum, mutationally activated CT-Ras induced abnormal hyphal proliferation and defects in polarized growth, and significantly reduced differentiation in a nutrient-dependent manner. These results show that C. trifolii Ras is a functional growth regulator in both mammals and fungi, and demonstrate that proper regulation of Ras is required for normal fungal growth and development.

3T3 Cells↗
PubMed1999

Cyclin D1 expression as a prognostic parameter in papillary carcinoma of the thyroid.

Papillary carcinoma of the thyroid is the most common thyroid cancer. At the time of clinical presentation, most papillary carcinomas are still confined to the thyroid gland, and appropriate surgical treatment achieves a 95% 5-year survival rate. Certain carcinomas, however, behave in a much more aggressive fashion. Because specific therapies do not exist, for those tumors that have escaped local control, patients with disseminated disease have little or no chance of permanent cure or long-term survival. Cyclin D1, a protein that plays a critical role in the control of the cell cycle, has been shown to be overexpressed in a variety of human neoplasias and may serve as a prognostic parameter of disease progression. To explore the role played by cyclin D1 in the pathogenesis of thyroid papillary carcinoma, we have quantitated, by computerized image analysis, the immunohistochemical expression of cyclin D1 in formalin-fixed, paraffin-embedded tissue from 35 conventional papillary carcinomas of the thyroid and correlated the results with established clinicopathologic parameters and available survival data.

Adult↗
PubMed1999

Genetic models with reduced penetrance related to the Y chromosome.

Classical statistical genetics models of a quantitative trait depending on an autosomal gene indicate that father-to-daughter and mother-to-son correlations should be the same. If phenotypes are not sex-dependent, father-to-son and mother-to-daughter correlations also share this common value. On the other hand, if the gene is sex-linked, then the father-to-son correlation is zero. Such models do not explain genetic variation in pulmonary artery pressure (PAP) of cattle--important because cattle with high PAP are known to develop brisket disease, pulmonary heart disease, and congestive heart failure when taken to high altitudes. Data on 966 calves at a ranch in Colorado showed positive correlation (0.2) between sire PAP and male calf PAP but slightly negative correlation (-0.01) between sire PAP and female calf PAP; the dam-to-male calf and dam-to-female calf correlations are both about 0.1. The model presented here postulates an autosomal gene with reduced penetrance (i.e., the trait may remain at a normal level even when the genotype suggests abnormality) and that, in males, the rate of penetrance is related to an abnormality in the Y chromosome and is therefore passed on from father to son. Then under plausible selective breeding assumptions, the pairwise correlation between fathers and daughters can become zero or negative. Explicit formulas are computed for the model covariances, and numerical computations indicate that plausible parameter values can be chosen for the model.

Altitude↗
PubMed1998

The effects of fluoride concentration and the level of cariogenic challenge on caries development in desalivated rats.

Dental caries is an infectious and transmissible disease that continues to affect the majority of people. The presence of carbohydrate, mainly sucrose in the diet, is an important factor in its occurrence. The amount of fluoride required for optimal protective effect where there is a high caries challenge is unclear. Differences in the intensity of cariogenic challenge, for whatever reason, may play a part in determining fluctuations in the effectiveness of fluoride. The purpose of this study was to evaluate the effect of different concentrations of fluoride on the development of caries and explore the cariostatic effect of fluoride under various levels of cariogenic challenge. The study comprises two experiments. In experiment I, 60 desalivated Sprague Dawley rats infected with Streptococcus sobrinus were offered the following to drink for 21 days: group (1), sterile distilled water (SDW); (2) 10 parts/10(6) F SDW; (3) 20 parts/10(6) F SDW; (4) 30 parts/10(6) F SDW; (5) 40 parts/10(6) F SDW. In experiment II, eight groups of 9 rats were placed in a König Höfer programmed feeder and were exposed to different levels of cariogenic challenge through varying frequency of eating and offered water containing 10 parts/10(6) F. In experiment I, exposure to 20, 30 and 40 parts/10(6) F reduced caries development significantly: fluoride, at 10 parts/10(6), reduced the severity of the carious lesions. In this model of severe cariogenic challenge, the results suggest that elevated concentrations of fluoride might be effective in patients at high caries risk. In experiment II, fluoride reduced the incidence and severity of smooth-surface caries in all groups. The protective effect of fluoride decreased as the number of exposures to sugar increased. It is concluded that the effectiveness of fluoride is influenced by the level of cariogenic challenge and that consideration should be given to adjusting the level of fluoride exposure based on perceived caries risk, and that there is a maximum therapeutic effect of fluoride beyond which no additional protection can be expected.

Animals↗
PubMed1998

A protein encoded by the latency-related gene of bovine herpesvirus 1 is expressed in trigeminal ganglionic neurons of latently infected cattle and interacts with cyclin-dependent kinase 2 during productive infection.

Despite productive viral gene expression in the peripheral nervous system during acute infection, the bovine herpesvirus 1 (BHV-1) infection cycle is blocked in sensory ganglionic neurons and consequently latency is established. The only abundant viral transcript expressed during latency is the latency-related (LR) RNA. LR gene products inhibit S-phase entry, and binding of the LR protein (LRP) to cyclin A was hypothesized to block cell cycle progression. This study demonstrates LRP is a nuclear protein which is expressed in neurons of latently infected cattle. Affinity chromatography indicated that LRP interacts with cyclin-dependent kinase 2 (cdk2)-cyclin complexes or cdc2-cyclin complexes in transfected human cells or infected bovine cells. After partial purification using three different columns (DEAE-Sepharose, Econo S, and heparin-agarose), LRP was primarily associated with cdk2-cyclin E complexes, an enzyme which is necessary for G1-to-S-phase cell cycle progression. During acute infection of trigeminal ganglia or following dexamethasone-induced reactivation, BHV-1 induces expression of cyclin A in neurons (L. M. Schang, A. Hossain, and C. Jones, J. Virol. 70:3807-3814, 1996). Expression of S-phase regulatory proteins (cyclin A, for example) leads to neuronal apoptosis. Consequently, we hypothesize that interactions between LRP and cell cycle regulatory proteins promote survival of postmitotic neurons during acute infection and/or reactivation.

Animals↗
PubMed1997

Analysis of cyclin-dependent kinase activity after herpes simplex virus type 2 infection.

Small DNA viruses (adenoviruses, simian virus 40, or human papillomaviruses) induce S-phase progression but prevent cell division to provide precursors for viral DNA replication. Herpes simplex viruses types 1 or 2 (HSV-1 or HSV-2) contain genes which encode DNA-metabolizing enzymes, for example, ribonucleotide reductase, thymidine kinase and dUTPase, suggesting that S-phase factors are not required for an efficient infection. However, several studies indicated that HSV induces some events that occur during cell-cycle progression. To determine if HSV-2 induces S-phase entry, we examined serum-arrested African green monkey kidney cells (CV-1) after infection. Two hours after infection steady-state levels of the S-phase-specific cyclin, cyclin A, increased. S-phase cyclin-dependent kinase activity (CDK2) was stimulated 10-fold 8 h after infection but decreased at 16 or 24 h after infection. Mitotic CDK activity (CDC2) was not activated after infection, in part due to decreases in CDC2 protein levels and inactivation of enzymatic activity resulting from tyrosine phosphorylation of CDC2. Furthermore, CDK4 activity was not dramatically affected by infection. These studies indicate that HSV-2 infection selectively activates CDK2 after infection but cell-cycle progression does not occur. We hypothesize that infection activates certain components of the cell cycle which enhance viral gene expression and DNA replication.

Animals↗