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Biomedical subjects

K W Thomas

Publications and source records attributed to K W Thomas.

At least 19 recordsLinked to original sources
PubMed2001

Simultaneous inhibition of Rac1 and IKK pathways sensitizes lung cancer cells to TNFalpha-mediated apoptosis.

Lung cancer is the most frequently occurring cancer in the world and causes more deaths in the United States than does colon, breast, and prostate cancer combined. Despite advances in treatment modalities including radiation, surgery, and chemotherapy, the overall survival in lung cancer remains low. The cytokine tumor necrosis factor alpha (TNFalpha) has been shown to regulate both apoptotic and antiapoptotic pathways. Activation of the transcription factor NF-kappaB appears to be the critical determinant of the antiapoptotic response to TNFalpha exposure in epithelial cells. A549 human lung carcinoma cells were infected with adenoviral constructs carrying dominant negative mutants of Rac1 and IKK or constitutively active mutant of Rac1, upstream effectors in TNF-mediated NF-kappaB activation. Cell death, apoptosis, and NF-kappaB activation were subsequently measured in response to TNFalpha exposure. Although TNFalpha alone had no cytotoxic effect, the expression of the dominant negative mutant of IKKbeta (Ad.IKKbetaKA) resulted in apoptotic cell death following TNFalpha exposure. Similarly, dominant negative mutant to Rac1 (Ad.N17Rac1) further sensitized A549 cells to IKKbetaKA-mediated TNFalpha-induced cell death. Conversely, a dominant active form of Rac1 (Ad.V12Rac1) ameliorated the cell death response to concurrent IKKbeta dominant negative mutant infection and TNFalpha exposure. These results suggest that concurrent inhibition of Rac1 and IKK pathways sensitizes lung cancer cells to TNFalpha-induced apoptosis.

Adenoviridae↗
PubMed1994

A breath sampling device for measuring human exposure to volatile organic compounds in microgravity.

A compact device for the collection of alveolar air (breath) from humans aboard spacecraft was developed. The system uses silicone one-way valves that operate independent of gravity, and provide minimal backpressure. Small charcoal filters clean ambient air used for inhalation. The device provided good recoveries of organic compounds at the 20 ng/L level, with generally low carryover of these compounds to a blank sample following a sample at exposure to 100 ng/L. When water accumulated in the system, this carryover increased for highly water soluble compounds. The new device was used in parallel with a larger, previously developed alveolar air sampler that requires gravity for proper operation; comparable results were obtained with the two units. The device measures 47 x 34 x 11.4 cm and weighs approximately 3.2 kg. Sufficient space is available within the case to accommodate a number of sample collection options.

Aerospace Medicine↗
PubMed1991

Elimination of volatile organic compounds in breath after exposure to occupational and environmental microenvironments.

Breath measurements offer the potential for a direct and noninvasive evaluation of human exposure to volatile organic compounds (VOCs) in the environments in which people live and work. This research study was conducted to further evaluate and develop the potential of this exposure assessment methodology. Several people were exposed to the atmosphere in six microenvironments for several hours. Air concentrations of VOCs were measured during these exposures and breath samples were collected and analyzed at multiple time points after the exposure to evaluate elimination kinetics for 21 VOCs. A new alveolar breath collection technique was applied. Elimination half-lives were estimated using a mono- and bi-exponential model. The alveolar breath collection and analysis methodology proved to be very useful for collecting many samples in short time intervals and this capability was very important for more accurately describing the initial phase of the decay curves. Breath decay curves were generated from samples collected over a four hour period after exposure for 21 of 24 target VOCs. A biexponential function generally provided a better fit for the decay data than did the monoexponential function, supporting a multi-compartment uptake and elimination model for the human body.

Air Pollutants↗
PubMed1991

Effect of dry-cleaned clothes on tetrachloroethylene levels in indoor air, personal air, and breath for residents of several New Jersey homes.

Several volatile organic compounds, including tetrachloroethylene, have been found to be nearly ubiquitous in residential indoor environments during previous TEAM studies. Eleven homes in New Jersey were monitored over three or five days to examine the effect of bringing freshly dry-cleaned clothes into the home on indoor air levels and personal exposures to tetrachloroethylene. Indoor air, personal air, and breath concentrations were measured over multiple 12-hrs periods before and after dry-cleaned clothes were introduced into nine of the homes. No dry-cleaned clothes were introduced into the two remaining homes. Outdoor air tetrachloroethylene concentrations were measured at six of the eleven homes. Indoor/outdoor concentration ratios and source strengths were calculated at the six homes with outdoor measurements. Elevated indoor air levels and human exposures to tetrachloroethylene were measured at seven of the nine homes with dry-cleaned clothes. Indoor air concentrations reached 300 micrograms/m3 in one home and elevated indoor levels persisted for at least 48 hrs in all seven homes. Indoor/outdoor tetrachloroethylene concentration ratios exceeded 100 for the four homes with both dry-cleaned clothes and outdoor measurements. Maximum source strengths ranged from 16 to 69 mg/hr in these homes and did not directly correspond to the number of dry-cleaned garments brought into the home. Breath levels of tetrachloroethylene increased two to six-fold for participants living in seven homes with increased indoor air levels. Indoor air, personal air, and breath tetrachloroethylene concentrations were significantly related (0.05 level) to the number of garments introduced divided by the home volume.

Air Pollutants↗
PubMed1990

Haemoglobinuria and hypophosphataemia in postparturient dairy cows without dietary deficiency of phosphorus.

Postparturient haemoglobinuria occurred in 11 Holstein-Friesian cows in 8 dairy herds in East Gippsland, Victoria. The affected cows had a wide range of ages, body condition and production level. Seven of 9 cows sampled were hypophosphataemic, 4 of 8 cows examined had Heinz bodies present in erythrocytes and strong ketonuria was present in 6 of 10 urine samples tested. Herdmates having similar calving dates had mostly normal serum phosphorus levels and none had Heinz bodies. There was no evidence for dietary phosphorus (P) deficiency, hypocuprosis or excessive P drain from high production being predisposing factors. There were no cruciferous plants in the diet. Haemolysis persisted in 4 cows despite treatment to raise serum P levels. An hyposthesis is proposed for the sporadic nature and clinical manifestations of the disease. This is based on mechanisms of hypophosphataemia occurring in man and mechanisms of Heinz body formation and haemolysis in other circumstances. We suggest that hypophosphataemia occurs following recovery from preparturient keto-acidosis caused by undernutrition in late pregnancy and then becoming nutritionally replete in the early postparturient period. Circulating oxidants may cause erythrocyte damage which may be predisposed to by hypophosphataemia.

Animals↗
PubMed1990

Thiamine deficiency in sheep exported live by sea.

Three shipments of sheep being exported live by sea were examined to determine their thiamine status. Measurements were made of thiamine concentration in liver and ruminal contents, transketolase activity in erythrocytes and thiaminase activity in ruminal liquor. Sheep that died or were clinically ill and euthanased had significantly lower hepatic and ruminal thiamine concentrations than clinically healthy control sheep. A high proportion had thiamine concentrations comparable to those found in sheep that die with polioencephalomalacia. Thiamine concentrations decreased with increasing time that sheep were in pre-embarkation feedlots and on board ship. Destruction of thiamine in the rumen by thiaminase was not a significant factor. Erythrocyte transketolase activities indicated that many of the sheep that arrived in the Middle East without signs of clinical disease were also in a state of thiamine insufficiency.

Animals↗
PubMed1987

Natural establishment of thiaminase activity in the alimentary tract of newborn lambs and effects on thiamine status and growth rates.

Thiaminase activity was detected in the faeces of lambs at 2 to 5 days of age. Levels of activity increased for 10 days and then declined over the next 3 to 4 weeks. Decreased erythrocyte transketolase activity indicated thiamine insufficiency in lambs with high thiaminase activity. Mean growth rates were 17% less in lambs with high thiaminase activity than in lambs with zero or low thiaminase activity. Bacillus thiaminolyticus was the only organism isolated which produced thiaminase. Treatment of newborn lambs with intramuscular injections of sulphadoxine did not prevent them from excreting thiaminase in their faeces. It is proposed that oral thiamine supplementation of lambs at 2 to 3 weeks of age may be the most appropriate prevention and treatment for subclinical thiamine deficiency of the cause described.

Animals↗
PubMed1986

The effect of thiaminase-induced subclinical thiamine deficiency on growth of weaner sheep.

Three experiments were performed to examine for causes of poor growth of young Merino sheep. Weekly testing of animals 42 weeks of age for 10 weeks revealed that 90% of clinically poor animals were excreting high levels of thiaminase in their faeces; low levels of activity were present in 20% of clinically normal animals. There were significant differences in the mean erythrocyte transketolase activity of the thiaminase excreting poor animals and the thiaminase free normal animals. Other known causes of poor growth could not be demonstrated. Weekly monitoring of thiaminase activity in the faeces from 80 lambs 6 weeks of age showed 23% to be excreting significant levels of enzyme (greater than 3mUg-1 DM) throughout a 10 week test period. Mean growth rates of these lambs were significantly below those of lambs not excreting thiaminase or excreting low levels intermittently. Supplementation of thiaminase excreting lambs with intra-muscular injections of thiamine HCl was associated with a statistically significant improved growth rate (P less than 0.01) compared to unsupplemented sheep excreting thiaminase. Mean growth rates of lambs not excreting thiaminase on a continuous basis (sampled weekly) were the same with or without thiamine HCl supplementation. High thiaminase levels were found in the ruminal fluids of trial animals excreting the enzyme in their faeces, confirming this previously established association. Bacillus thiaminolyticus was isolated from faeces and ruminal fluids from clinically poor animals and is the most likely source of the thiaminase. Subclinical thiamine deficiency was indicated by low erythrocyte transketolase activities and elevated TPP effects and is proposed as the cause of the poor growth by the young sheep.

Aging↗
PubMed1986

Oral treatment of polioencephalomalacia and subclinical thiamine deficiency with thiamine propyl disulphide and thiamine hydrochloride.

Thiaminase type I production by Bacillus thiaminolyticus and activity in vitro were repressed by the primary substate thiamine and by thiamine monophosphate and thiamine propyl disulphide. At thiamine concentrations of 300-3000 mumol/l production of active enzyme by B. thiaminolyticus, and activity of purified enzyme, were totally repressed. Growth of B. thiaminolyticus was inhibited by thiamine propyl disulphide at 3000 mumol/l. Activity of purified thiaminase was lost when incubated with ruminal fluid from healthy thiaminase free sheep. Enzyme activity was also lost when exposed to mildly alkaline conditions but was stimulated and stabilized against heat denaturation if treated with dithiothreitol. Thiaminase activities in the ruminal fluids of cases of ovine polioencephalomalacia were repressed within 2 h of oral administration of thiamine propyl disulphide. Blood pyruvate levels and transketolase activities were restored to normal following treatment. Treated animals recovered clinically and were returned to pasture.

Administration, Oral↗
PubMed1984

Levels of trace elements in the liver and diet of free-living koalas, Phascolarctos cinereus (Goldfuss).

The mean liver concentrations of copper, manganese, zinc and cobalt were 0.25, 0.20, 2.97 mmol/kg and 2.81 mumol/kg respectively in free-living koalas in Victoria, Australia. The mean plasma copper concentration was 9.2 mmol/liter which was somewhat below the level in other hindgut fermenters. The mean concentrations of copper, manganese and zinc in their diet (Eucalyptus spp.) were 0.08, 4.46 and 0.27 mmol/kg respectively. Analysis of the data established a significant correlation between the age of the koalas and the inverse of the concentration of the copper (r = -0.67, P less than 0.001) in the liver. There were no such correlations apparent for manganese, zinc or cobalt. The concentrations of trace metals in the Eucalyptus diet for the koala were comparable to those recommended in the diets for other hindgut fermenters such as horse, rabbits and rats. However there was evidence for suboptimal plasma copper levels (mean 9.2 mmol/liter) in some koalas, and reduced liver copper levels in older koalas. Liver histology revealed the presence of brown intracytoplasmic granules in hepatocytes. The size and number of these granules per cell was noted to increase with increasing age of the koala but the chemical nature and the role of the granules was not determined by the histochemical techniques used.

Age Factors↗
PubMed1982

White liver disease of sheep.

Outbreaks of ovine white liver disease (WLD) on 7 farms in eastern Victoria were investigated. Most occurred in late spring and mainly affected lambs 3 to 6 months old, with a morbidity of 20 to 100% and mortality of 8 to 15%. Clinically affected lambs showed illthrift, emaciation and bilateral, serous, ocular discharge. Clinical pathology showed mild anaemia, elevated serum liver enzymes (GGT, OCT, AST) and low levels of serum vitamin B12. Grossly, the livers were pale, fatty and friable; microscopically there was parenchymal fatty change, bile duct proliferation and ceroid pigmentation. Liver cobalt values were consistently low (mean 0.4 +/- 0.4 mumol/kg D.W.). Levels of cobalt in pasture from 2 properties were very low (0.34 mumol/kg D.W.) The diagnosis of white liver disease was made on the basis of clinical features, specific liver pathology and low cobalt status. Treatment trials established that cobalt injections or oral bullet administration resulted in clinical improvement, significant weight gains, and improved serum vitamin B12 levels. WLD did not recur in previously affected sheep using these treatments. However, when blocks containing cobalt were available continuously, WLD recurred 2 years after the initial outbreak.

Animals↗
PubMed1982

Beyond expectancy theory: an integrative motivational model from health care.

Expectancy theory has been criticized for its omission of normative, habitual, and other motivational elements. This paper describes the sources and features of an integrative motivational model from the field of preventive health care that combines expectancy/valence factors with habitual, normative, and conative motivational elements. The model is viewed as having implications for work motivation as well.

Analysis of Variance↗
PubMed1980

The use of immunochemically purified anti-brucella antibody in a direct fluorescent antibody test for Brucella abortus.

Antibodies specific for Brucella abortus were purified from the serum of hyperimmunized sheep using immunochemical procedures. They were conjugated to fluorescein isothiocyanate and used in a fluorescent antibody (FA) test for B. abortus. The conjugate did not stain any heterologous bacterial or fungal species tested and background fluorescence associated with its use on smears and sections of abortion materials was particularly low. Of 239 cases of abortion examined fluorescent microscopy demonstrated B. abortus in all 12 cases in which the organism was isolated. A few areas of fluorescence typical of B. abortus were also seen in 3 cases from which the organism was not cultured. B. abortus was demonstrated in lymph nodes from 6 of 36 Brucella reactor cows by culture and 7 by the FA test. However, only very low numbers of B. abortus were isolated or seen and sampling errors would have been significant. Use of the FA test allows diagnosis of Brucellosis to be made in 2 hours, compared to 6 days by the usual cultural procedures.

Aborted Fetus↗