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Biomedical subjects

T Tyler

Publications and source records attributed to T Tyler.

At least 19 recordsLinked to original sources
PubMed2001

Tumor suppression and therapy sensitization of localized and metastatic breast cancer by adenovirus p53.

We have examined the effects of a replication-defective adenovirus encoding p53 (RPR/INGN 201 [Ad5CMV-p53]; Adp53), alone or in combination with the breast cancer therapeutic doxorubicin (Adriamycin), to suppress growth and induce apoptosis in breast cancer cells in vitro. We have also examined the in vivo effect of intratumoral administration of Adp53, alone or in combination with doxorubicin, to suppress the growth of established subcutaneous MDA-MB-435 breast cancer tumors. Finally, using the MDA-MB-435 orthotopic model of metastatic breast cancer, we have examined the effect of systemic administration of Adp53, alone or in combination with doxorubicin, to reduce the incidence of metastases. We find that whereas in vitro treatment of cells with Adp53 reduces [(3)H]thymidine incorporation by about 90% at 48 hr, cell viability at 6 days is reduced by only some 50% relative to controls. Although apoptosis is detectable in Adp53-treated cultures, these results suggest that a large fraction of Adp53-treated cells merely undergo reversible cell cycle arrest. Combined treatment with Adp53 and doxorubicin results in a greater than additive loss of viability in vitro and increased apoptosis. In vivo, locally administered Adp53 suppresses growth of established subcutaneous tumors in nude mice and suppression is enhanced by doxorubicin. In the metastatic breast cancer model, systemic administration of Adp53 plus doxorubicin leads to a significant reduction in the incidence of metastases relative to Adp53 or doxorubicin alone. Taken together, these data indicate an additive to synergistic effect of Adp53 and doxorubicin for the treatment of primary and metastatic breast cancer.

Adenoviridae↗
PubMed1999

Obtaining an accepted Investigational New Drug application to operate an umbilical cord blood bank.

BACKGROUND: The residual blood left in the placenta, previously considered a biologic waste, contains sufficient hematopoietic stem and progenitor cells to consistently engraft at least a small recipient. Over the past several years, more than 500 HLA-matched, related and unrelated, allogeneic cord blood transplants have been performed. Consequently, public and private cord blood banks are being developed to meet future demands. Thus, the definition of a suitable and effective cord blood component needs to be critically defined. In February 1997, the US Food and Drug Administration (FDA) proposed that cord blood banks should operate under an Investigational New Drug (IND) license. STUDY DESIGN AND METHODS: Standard operating procedures were designed using standards from the Foundation for Accreditation of Hematopoietic and Cellular Therapy, the American Association of Blood Banks, and the National Marrow Donor Program and in accordance with current good manufacturing practices. The standard operating procedures were field-tested and submitted to the FDA. RESULTS: Issues of the utmost concern to the FDA dealt with transplant recipient outcome data collection, donor recruitment, sample tracking, the use of unlicensed materials, and the reporting of positive infectious disease results. After three attempts, an IND application was approved. CONCLUSIONS: To obtain approval of an IND application, cord blood banks need a set of standard operating procedures that describe cord blood collection, processing, freezing, and storage. Issues relating to potential cord blood recipient identification, cord blood shipping, and reporting of transplant recipient outcomes are also needed. The IND process provides an opportunity for outside reviewers to make suggestions that may be included in the standard operating procedures.

Blood Banks↗
PubMed1997

Isopropanol vapor inhalation oncogenicity study in Fischer 344 rats and CD-1 mice.

The potential oncogenic effects of isopropanol, a widely used solvent, were investigated. Four groups of animals, each consisting of 75 CD-1 mice/sex and 75 Fischer 344 rats/sex, were exposed to isopropanol vapor (CAS No. 67-63-0) at target concentrations of 0 (filtered air control), 500, 2500, or 5000 ppm. Animals assigned to the core group (55 mice/sex/group and 65 rats/sex/group) were exposed for 6 hr/day, 5 consecutive days/week for at least 78 weeks for the mice or 104 weeks for the rats. Ten mice/sex/group and 10 rats/sex/group were assigned to an interim euthanasia group and were terminated during Weeks 54 and 73, respectively. In addition, 10 mice/sex/group were assigned to a recovery group and did not receive any further exposure following Week 53 but were retained until the core group of animals was euthanized. Transient signs of narcosis were observed for both mice and rats during exposure to 2500 and 5000 ppm and following exposure for mice from the 5000-ppm group. Increased mortality (100% versus 82% for controls) and a decreased mean survival time (577 days versus 631 days for controls) were noted for male rats from the 5000-ppm group. Increases in body weight and/or body weight gain were typically observed for both sexes of mice and rats from the 2500- and 5000-ppm groups throughout the study. Urinalysis and urine chemistry changes indicative of impaired kidney function (i.e., decreased osmolality and increased total protein, volume, and glucose) were noted for male rats from the 2500-ppm group as well as for male and female rats from the 5000-ppm group. At the interim euthanasia, a concentration-related increase in testes weight (absolute and relative as a percentage of body and brain weight) was observed for male rats. Concentration-related increases in absolute and relative liver weight (as a percentage of body weight) were observed for male and female mice. In addition, increased absolute and/or relative (as a percentage of body and brain weight) liver and kidney weights were observed for male and/or female rats from the 2500- and 5000-ppm groups. At necropsy, an increased incidence of seminal vesicle enlargement was observed grossly for male mice from the 2500- and 5000-ppm groups. Microscopically, some of the nonneoplastic lesions noted for mice included an increased incidence of ectasia of the seminal vesicles for male mice from the 2500- and 5000-ppm groups, minimal renal tubular proteinosis for male and female mice from all isopropanol groups, and renal tubular dilation for female mice from the 5000-ppm group. A number of nonneoplastic lesions were observed for male and female rats from the 2500- and 5000-ppm groups, with the most significant lesions being observed in the kidney and associated with chronic renal disease. The lesions noted with increased severity and/or frequency included mineralization, tubular dilation, glomerulosclerosis, interstitial nephritis, interstitial fibrosis, hydronephrosis, and transitional cell hyperplasia. The only tumor type increased in incidence during the study was interstitial cell adenomas of the testes in male rats. However, the increase in these adenomas was not believed to be exposure-related due to an unusually low incidence observed for the control group. There were no increased frequencies of neoplastic lesions noted for male or female mice or for female rats from any isopropanol exposure group. Chronic renal disease was attributed to be the main cause of death for male and female rats from the 5000-ppm group and was also considered to account for much of the mortality observed for male rats from the 2500-ppm group. In conclusion, the no-observed-effect level (NOEL) for toxic effects for both rats and mice was 500 ppm. The NOEL for oncogenicity effects for both mice and rats was determined to be greater than 5000 ppm.

1-Propanol↗
PubMed1996

A new pelvic tilt detection device: roentgenographic validation and application to assessment of hip motion in professional ice hockey players.

Professional ice hockey players often sustain hip and low back strains. We hypothesized that playing the sport of ice hockey may result in the shortening of the iliopsoas muscles, increasing the likelihood of lumbosacral strains and hip injuries. The purpose of this study was to identify whether ice hockey players demonstrate a decrease in hip extension range of motion when compared with age-matched controls. Objective data were obtained using the Thomas test with an electrical circuit device to determine pelvic tilt motion. The device was validated by obtaining X-rays in six subjects during the Thomas test. The study then examined 25 professional hockey players and 25 age-matched controls. A two-way analysis of variance was applied for statistical analysis to examine the effect of sport and side. The results demonstrated that ice hockey players have a reduced mean hip extension range of motion (p < .0001) by comparison with age-match controls. There was no difference between right and left sides, nor was there any interaction of the sport with the side of the body. Therefore, hockey players demonstrated a decreased extensibility of the iliopsoas muscles. Future research may be directed toward establishing a link between prophylactic stretching and injury rate in professional ice hockey players.

Age Factors↗
PubMed1985

Quantitative assessment of in vivo backscatter enhancement from gelatin microspheres.

Experimental work using a quantitative C-scan technique to measure in situ enhancement of hepatic backscatter resulting from the administration of gelatin microspheres to dogs is reported. We have found that reproducible enhancement of hepatic backscatter on the order of 2 dB followed the peripheral administration of gelatin within minutes, the magnitude of the effect was not sensitive to the rate of infusion, but was likely to be dose dependent, changes in the overlying tissue attenuation had a pronounced effect on the measurement, and the effect was sustained for up to one half hour or longer.

Animals↗
PubMed1980

Oligohydramnios and transient neonatal anuria: a possible association with the maternal use of prostaglandin synthetase inhibitors.

The chronic use of prostaglandin synthetase inhibitors is reported in a pregnant patient with severe juvenile rheumatoid arthritis. Aspirin and indomethacin, along with corticosteroids, were required to prevent significant progression of the disease. Pregnancy was complicated by oligohydramnios and intrauterine growth retardation. The infant suffered transient anuria. The effects of prostaglandin synthetase inhibitors on renal vascular function is reviewed, and a possible association between the chronic ingestion of these drugs and compromised renal function in the newborn is pointed out.

Adult↗
PubMed1979

Pulmonary and systemic vascular responses of perinatal goats to prostaglandins E1 and E2.

Effects of prostaglandins of the E series and their metabolites on pulmonary and systemic circulations of newborn and exteriorized fetal goats (anesthetized with chloralose) were evaluated in situ using an isolated perfused left lung lobe preparation. Prostaglandin E1 (PGE1) and, to a lesser extent, prostaglandin E2 (PGE2) infusions resulted in decreases of pulmonary vascular resistance (PVR) of fetal and neonatal goats. Infusions of PGE1 or PGE2 (less than 2 microgram.kg-1.min-1 for 1 min) directly into left pulmonary arterial blood did not affect systemic arterial pressure (SAP). Infusions of PGEs (greater than 2 microgram.kg-1.min-1 for 1 min) resulted in decreases in SAP and heart rate. The dose-response characteristics of the pulmonary circulation in response to PGE1 and PGE2 were not different in fetal and newborn goats. Fetal asphyxia did not alter the dose-response characteristics of pulmonary circulation in response to PGE1. Metabolites (15-keto) of PGE1 and PGE2 had no effect upon PVR or SAP of perinatal goats. These results demonstrate in perinatal mammals 1) vasodilator action of PGE1 and PGE2 on the pulmonary and systemic circulations, and 2) catabolism by the lungs of these prostaglandins.

Animals↗
PubMed1978

Sodium transport by isolated bullfrog small intestine. Effect of prostaglandin E1.

Addition of 446 micron prostaglandin E1 (PGE1) to the serosal medium of isolated short-circuited bullfrog small intestine elicited small increases transmural potential difference and short-circuit current while addition of PGE1 to the mucosal medium caused no change in the electrical parameters. Addition of 100 micron indomethacin to the mucosal medium inhibited both potential difference and short-circuit current with a resultant increase in steady-state tissue resistance. In the presence of mucosal 100 micron indomethacin, serosal 60 micron PGE1 markedly stimulated transmural potential difference and short-circuit current with a resultant decrease in steady-state tissue resistance. Serosal arachidonic acid (330 micron) stimulated transmural potential difference and short-circuit current and this effect was abolished by the addition of 100 micron indomethacin to the mucosal medium. Serosal 60 micron PGE1 only stimulated the M (mucosa) leads to S (serosa) unidirectional flux of sodium. These results strongly suggest that the PGE1 action is mediated either via a series of metabolic reactions which possibly increase the permeability of the mucosal membrane to sodium or via direct stimulation of rheogenic sodium pump activity.

Animals↗
PubMed1977

Heat production of fetal sheep brain in utero.

Thermojunctions were implanted in the brains of 10 near term fetal sheep in utero under halothane anesthesia. Brief total occlusion of fetal brachiocephalic artery was followed immediately by an increase in brain temperature (mean +/- SE) of 0.130 +/- 0.014 degrees C-min-1. Occlusion of main pulmonary artery and ascending aorta, simultaneously, led to a brain temperature increase of 0.144 +/- 0.018 degrees C-min-1. Specific heat of three fetal brains was determined to be 0.898 +/- 0.014 cal-g-1. degrees C-1 or 3.76 +/- 0.059 J-g-1. Rate of fetal brain heat production, computed as the product of the higher rate of temperature change and brain specific heat, was 0.129 +/- 0.014 cal-g-1-min-1 or 9.00 +/- 0.98 mW-g-1.

Animals↗
PubMed1976

Use of indomethacin to reverse neonatal hypotension.

Treatment with indomethacin elevated systemic arterial pressure and pulmonary vascular resistance in hypotensive newborn goats. Indomethacin may be of value in restoration of systemic arterial pressure in stress-induced hypotension.

Animals↗
PubMed1976

Idiopathic multicentric osteolysis.

A 59 year old while female with striking carpal and tarsal osteolysis is reported. The process primarily involves the carpals and tarsals but includes other sites. The pertinent literature is reviewed and a simplified classification of idiopathic multicentric osteolysis is presented. Idiopathic multicentric osteolysis may be sporadic but can demonstrate either dominant or recessive inheritance. There may or may not be associated nephropathy. The underlying mechanism appears similar in all variations of this condition. Gorham's disease, the Winchester syndrome, and other osteolytic conditions which may predominantly affect the tarsal and carpal bones most likely are totally different processes, unrelated to idiopathic multicentric osteolysis.

Arthritis, Juvenile↗
PubMed1975

Effects of prostaglandins of the E-series on pulmonary and systemic circulations of newborn goats during normoxia and hypoxia.

Effects of exogenous prostaglandins of the E-series on pulmonary and systemic circulations of newborn goats were investigated during normoxia and hypoxia. Pulmonary arterial infusion of prostaglandins E1 and E2 decreased pulmonary vascular resistance 20% and 14%, respectively, without systemic effects. Prostaglandin E1 abolished the pulmonary pressor response to hypoxia. Prostaglandin E2 was less effective in counteracting this hypoxic response. The increased pulmonary vascular resistance and augmented response to hypoxia following indomethacin administration was reversed by prostaglandin E1. Infusion of prostaglandin E1 directly into the pulmonary circulation may be of benefit to the distressed newborn with elevated pulmonary vascular resistance.

Animals↗
PubMed1975

The effects of prostaglandin E on fetal pulmonary vascular resistance (38588).

The effects of PGE on pulmonary vascular resistance were investigated in fetal goats using an isolated perfusion technique on otherwise intact unventilated lobes. PGE decreased perfusion pressure in the left pulmonary artery under conditions of monary vascular resistance by vasodilatation of tonically contracted vascular smooth muscle. In our preparation, intrapulmonary PGE infusion did not alter femoral arterial pressure which suggests that PGE is inactivated in the fetal lung. Implications for PGE in the newborn with respiratory distress and increased pulmonary vascular resistance are discussed.

Animals↗