Biomedical subjects

J Doty

Publications and source records attributed to J Doty.

12 recordsLinked to original sources

PubMed2005

Discovery of the short gamma-ray burst GRB 050709.

Gamma-ray bursts (GRBs) fall into two classes: short-hard and long-soft bursts. The latter are now known to have X-ray and optical afterglows, to occur at cosmological distances in star-forming galaxies, and to be associated with the explosion of massive stars. In contrast, the distance scale, the energy scale and the progenitors of the short bursts have remained a mystery. Here we report the discovery of a short-hard burst whose accurate localization has led to follow-up observations that have identified the X-ray afterglow and (for the first time) the optical afterglow of a short-hard burst; this in turn led to the identification of the host galaxy of the burst as a late-type galaxy at z = 0.16 (ref. 10). These results show that at least some short-hard bursts occur at cosmological distances in the outskirts of galaxies, and are likely to be caused by the merging of compact binaries.

Journal Article↗

PubMed1999

Cigarette smoke impairs endothelium-dependent relaxation in rabbit superficial femoral veins.

BACKGROUND: The use of autogenous vein for arterial reconstruction provides the optimal conduit for limb salvage. Cigarette smoking is a risk factor for vascular disease and may adversely affect graft patency and limb preservation rates of extremities reconstructed with autogenous vein. This study was performed in order to determine the effects of cigarette smoke on venous endothelium-dependent relaxation which is mediated by nitric oxide. MATERIALS AND METHODS: New Zealand white rabbits were exposed to cigarette smoke in a 240-ft3 air-flow chamber for 3 h per day, 5 days per week, for 8 weeks. A control group was treated similarly without infusion of smoke into the chamber. Elevated serum cotinine and carboxyhemoglobin levels comparable to those of chronic smokers were observed in the experimental group. After 8 weeks, the superficial femoral veins were explanted, cut into 3-mm segments, and studied in organ chambers. RESULTS: No difference in contractile response to KCl (80 mM) (control, 0.10 +/- 0.06; smoke, 0.17 +/- 0.04) or norepinephrine (EC50) (control, 0.78 +/- 0.18; smoke, 0.87 +/- 0.11) was seen. A significant decrease in relaxation was noted with all doses of acetylcholine (M) (control, 10(-8) - 50.35 +/- 8.37, 3 x 10(-8) - 71.20 +/- 9.05, 10(-7) - 88.32 +/- 13.72, 3 x 10(-7) - 92. 86 +/- 13.69; and smoke, 10(-8) - 8.25 +/- 1.83*, 3 x 10(-8) - 19.11 +/- 5.11*, 10(-7) - 31.84 +/- 7.90*, 3 x 10(-7) - 39.74 +/- 8.65*; *P < 0.05). Both control and smoke veins relaxed completely with sodium nitroprusside. CONCLUSIONS: Superficial femoral veins, when exposed to cigarette smoke, demonstrated a significant decrease in endothelium-dependent relaxation in response to acetylcholine without smooth muscle injury. This loss of vasomotor tone could be detrimental over time in veins which have been placed as arterial conduits.

Acetylcholine↗

PubMed1997

Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase.

The epidermal growth factor receptor (EGFR) is overexpressed in a significant percentage of carcinomas and contributes to the malignant phenotype. CP-358,774 is a directly acting inhibitor of human EGFR tyrosine kinase with an IC50 of 2 nM and reduces EGFR autophosphorylation in intact tumor cells with an IC50 of 20 nM. This inhibition is selective for EGFR tyrosine kinase relative to other tyrosine kinases we have examined, both in assays of isolated kinases and whole cells. At doses of 100 mg/kg, CP-358,774 completely prevents EGF-induced autophosphorylation of EGFR in human HN5 tumors growing as xenografts in athymic mice and of the hepatic EGFR of the treated mice. CP-358,774 inhibits the proliferation of DiFi human colon tumor cells at submicromolar concentrations in cell culture and blocks cell cycle progression at the G1 phase. This inhibitor produces a marked accumulation of retinoblastoma protein in its underphosphorylated form and accumulation of p27KIP1 in DiFi cells, which may contribute to the cell cycle block. Inhibition of the EGFR also triggers apoptosis in these cells as determined by formation of DNA fragments and other criteria. These results indicate that CP-358,774 has potential for the treatment of tumors that are dependent on the EGFR pathway for proliferation or survival.

Adenosine Triphosphate↗

PubMed1997

The Cyberknife: a frameless robotic system for radiosurgery.

The Cyberknife is a unique instrument for performing frameless stereotactic radiosurgery. Rather than using rigid immobilization, the Cyberknife relies on an image-to-image correlation algorithm for target localization. Furthermore, the system utilizes a novel, light-weight, high-energy radiation source. The authors describe the technical specifications of the Cyberknife and summarize the initial clinical experience.

Algorithms↗

PubMed1996

Relationship between intrinsic radiation sensitivity and metastatic potential.

PURPOSE: Prior studies emphasized genetic modulation of tumorigenicity, and experimental metastatic potential in cells transfected with oncogenes. Whether the intrinsic radiaton sensitivity of cells might correlate with parallel changes in metastatic potential is unknown. METHODS AND MATERIALS: Rat embryo cells (REC) were transfected with the following oncogenes, and where appropriate, with corresponding selection markers: pCMVneopEJ6.6ras, pEJ6.6ras/v-myc, pEla, and pEJ6.6ras/Ela. Individual transfectant clones and corresponding pooled cellular populations were propagated in selective medium. In vitro cellular radiation sensitivity was determined via clonogenic assays, a minimum of three, by standard techniques and individual SF2 and MID parameters determined. Tumorigenicity was defined as the number of tumors forming following the injection of 1 x 10(5) - 1 x 10(6) cells into the axillary pouch of three different strains of immune-deficient mice. Animals were killed once resultant tumors reached a maximum size of 1.5-2.0 cm in maximum diameter. For determination of experimental metastatic potential, between 1 x 10(5) - 1 x 10(6) cells were injected into the tail veins of litter-matched sibling mice in parallel to the tumorigenicity studies. RESULTS: Radiobiologic studies indicate similar levels of radiation sensitivity among REC, mock-transfected REC, Ela, and combined E1a/ras transfectants. pEJ6.6ras, and combined ras/myc transfected pooled cellular populations demonstrated increases in radiation resistance when compared to the pooled radiobiologic data from untransfected and mock-transfected corresponding pooled cellular populations (p <0.05, two-tailed test, SF2, MID). Rat embryo cells, Ela, and mock-transfectants were relatively radiation sensitive and nontumorigenic. pEla/ras was tumorigenic but demonstrated relatively low experimental metastatic potential. Ras, and ras/myc transfectants, demonstrated similar levels of experimental metastatic potential on lung colonization assays. CONCLUSIONS: A good correlation exists between the intrinsic radiation sensitivity and the experimental metastatic potential of transfected REC. The highest levels of radiation resistance in vitro and experimental metastatic potential in vivo were found among REC transfected with ras/myc or activated ras alone. E1a/ ras cotransfected cellular populations, although tumorigenic, were relatively radiation sensitive and nonmetastatic. Further study is needed to formulate a mechanistic explanation for the intriguing correlation between intrinsic radiation sensitivity in vitro and metastatic potential in vivo.

Adenovirus E1A Proteins↗

PubMed1991

Development of squamous cell carcinoma in chronic perineal sinus and wounds in Crohn's disease.

Two patients with Crohn's disease who developed squamous cell carcinoma in chronic sinus tracts are reported. Because nonhealing perineal sinus tracts or fistulas are relatively common in patients with Crohn's disease, the diagnosis of carcinoma may not be considered until the malignancy is advanced. Because of the potential for a surgical and oncologic "cure," early diagnosis may improve the prognosis. Malignancy should be considered in patients with nonhealing perineal sinuses who develop severe continuous perianal pain. Diagnosis is best made by needle aspiration cytology and sinus tract biopsy. Treatment should include wide excision of the sinus tract, surrounding soft tissue, and lymph nodes, followed by chemotherapy and radiotherapy in selected cases.

Adult↗

PubMed1990

Gastric emptying of nondigestible solids in dogs: a hydrodynamic correlation.

The influence of particle size, particle density, fluid viscosity, and fluid flow rate on the gastric emptying of nondigestible solids was investigated in five dogs with chronically placed fistulas. Six hundred and fifty particles of 13 different size and density combinations were administered simultaneously with 500 ml of either normal saline or low-, medium-, or high-viscosity polymer solutions. The canine stomach was found to discriminate between these solids on the basis of size and density at all levels of viscosity above saline. The observed patterns of emptying are consistent with the hypothesis that gastric emptying of nondigestible solids is governed in part by hydrodynamics and correlate well with the gastric-emptying coefficient (GEC), a dimensionless grouping of variables that takes the form GEC = (Dpy/Dp) [g(rho f - rho p)Dp2]/[eta (nu)] where [g(rho f - rho p)] is particle buoyancy consisting of fluid (rho f) and particle (rho p) densities and g, the gravitational constant; (Dp) is the particle diameter, (Dpy) the estimated pyloric diameter, eta the fluid viscosity, and (nu) the average linear velocity of fluid exiting the stomach.

Animals↗

PubMed1986

Enhanced gallbladder absorption during gallstone formation: the roles of cholesterol saturated bile and gallbladder stasis.

Cholesterol saturated bile and gallbladder stasis are important factors in the pathogenesis of cholesterol gallstones. The degree to which either or both of these factors affect gallbladder transport of fluid remains obscure. The authors tested the hypothesis that both cholesterol saturated bile and gallbladder stasis, and not stasis alone, promotes gallbladder fluid absorption. Prairie dogs were maintained for 2 weeks on either a control chow, total parenteral nutrition (TPN), or a 1.2% cholesterol enriched chow. The bile acid pool was labeled with 14C-cholic acid and indexes for cholesterol saturation (CSI) and gallbladder stasis (Rsa) were determined. Fluid transport was indirectly measured by calculating the ratio of gallbladder to hepatic bile concentrations of individual and total biliary lipids. Despite evidence of stasis in prairie dogs maintained on TPN, bile was unsaturated, and gallbladder absorption was not appreciably changed. In contrast, cholesterol-fed animals had cholesterol supersaturated bile, gallbladder stasis, and altered gallbladder absorption, as manifested by a significant change in the ratio of gallbladder to hepatic bile concentrations of individual and total biliary lipids. These data suggest that both cholesterol saturated bile and gallbladder stasis, and not stasis alone, are essential in promoting the enhanced gallbladder absorption, which has previously been observed during early cholesterol gallstone formation.

Absorption↗

PubMed1985

Anomalous drainage of the common bile duct into the fourth portion of the duodenum. Clinical sequelae.

We report two cases of early-childhood anomalous drainage of the common bile duct (CBD) into the fourth portion of the duodenum, which caused recurrent abdominal pain and hyperamylasemia. In both patients, this anomaly was associated with a long common channel between the CBD and the pancreatic duct. The CBD was obstructed by compression from the first portion of the duodenum, which passed anteriorly. Both children required choledochoenteric anastomosis to achieve permanent resolution of the abdominal pain. Elevation of the first portion of the duodenum does not produce permanent relief from symptoms. We believe that these patients represent the first described to have this unusual malformation.

Abdomen↗

PubMed1982

Amebic abscess of the liver: surgical aspects.

During the past five years, ten documented cases of hepatic amebic abscess have required surgical intervention at Olive View Hospital, Van Nuys, California. Three of the patients underwent laparotomy when an hepatic abscess ruptured into the peritoneal cavity, and two required surgical intervention when an abscess invaded adjacent organs. Another abscess continued to enlarge despite metronidazole therapy and still another became superinfected with bacteria. In the remaining three patients, surgical procedure would have been avoided if the correct diagnosis had been made. In fact, the preoperative diagnosis in five cases was acute appendicitis. All patients survived. The incidence of Entamoeba histolytica infestation is increasing in our community. Although most patients rapidly improve with metronidazole therapy, surgical complications do arise and diagnoses are missed. This series of cases emphasizes the need for surgeons working in Southern California to familiarize themselves with the clinical features, complications and appropriate surgical treatment of amebiasis.

Abdomen, Acute↗

PubMed1977

Cyclic AMP response to prostaglandin E1 in mononuclear cells from peripheral blood and synovial fluid of patients with rheumatoid arthritis.

The cyclic AMP response to prostaglandin E1 (PGE1) was studied in peripheral blood (PB) and synovial fluid (SF) mononuclear cells from patients with rheumatoid arthritis (RA). The PGE1 induced accumulation of cyclic AMP was consistently (7 of 8 patients) less in cell suspensions derived from SF than in suspensions of equivalent numbers of mononuclear cells obtained simultaneously from PB. The high PB/SF cyclic AMP ratio was seen most clearly at the lowest concentration (10(-6)M) of PGE1 tested. There was no correlation between the patients' therapy and cyclic AMP response to PGE1. The high PB/SF cyclic AMP ratio was not accounted for by the presence of platelets in PB cell suspensions.

Arthritis, Rheumatoid↗

PubMedDate not supplied

Refractive surgery and the athlete.

1. Athletes and medical professionals alike need to understand the basic methods of the new techniques, limitations, and benefits in refractive surgery as the field continues to offer new avenues in optical correction. 2. Wearing the appropriate protective eye wear is crucial to the health of the eyes, regardless of whether surgery has already been performed. The eyes are vulnerable to a variety of potential injuries, and proper care should be taken when participating in sports, especially for those who have undergone eye surgery. 3. The four basic surgical procedures presently in common practice each offer their own unique advantages to improving eyesight, and each has differing risks and residuals involved in the procedures.

Corneal Transplantation↗