Thymineless death in colon carcinoma cells is mediated via fas signaling

Fas is expressed constitutively in colonic epithelial cells and is also expressed in colon carcinomas and in cultured colon carcinoma cell lines. However, the potential role of Fas signaling in mediating apoptosis in cells of this type remains unknown. We have developed human colon carcinoma cell models deficient in thymidylate synthase that demonstrate acute (TS- cells) or delayed (Thy4 cells) apoptosis following DNA damage induced by thymineless stress. Complete protection of cells from acute apoptosis and prolongation of delayed apoptosis was obtained following exposure to the NOK-1 monoclonal antibody (inhibitory to Fas signaling) during the period of dThd deprivation. These results suggested that apoptosis induced by thymineless stress was regulated by autocrine signaling via Fas-FasL interactions. Fas expression was high in both TS- and Thy4 cells. However, FasL, undetectable in synchronous cultures, was up-regulated in TS- cells at 48 hr, when cells were undergoing acute apoptosis, and in Thy4 cells at 96 hr, correlating with the delayed onset of thymineless death. FasL expression also correlated with acute apoptosis induced in parental GC3/cl cells, commencing at 48 hr, following thymidylate synthase inhibition by 5-fluorouracil/leucovorin exposure. Fas-mediated apoptosis induced by the cytotoxic anti-Fas monoclonal antibody CH-11 was inhibited following adenoviral delivery of a Bcl-2 cDNA, and Bcl-2 also protected cells from acute apoptosis induced by dThd deprivation. Taken together, these data demonstrate a functional Fas system in these cultured colon carcinoma cell models, and they demonstrate that Fas-FasL interactions can link DNA damage induced by thymineless stress to the apoptotic machinery of colon carcinoma cells.     

Safety of influenza vaccine in heart transplant recipients

BACKGROUND: Influenza vaccine is recommended for heart transplant recipients, but its administration is often deferred because of anecdotal reports of rejection associated with the vaccine. We evaluated the safety of influenza vaccine in a group of stable heart transplant recipients over a 2-year period. METHODS: During the 1993 to 1994 influenza season, stable heart transplant recipients who had undergone transplantation a minimum of 1 year before study entry were randomized to vaccination with a single dose of influenza vaccine versus no vaccination. Routine endomyocardial biopsies and postvaccination influenza serologic studies were performed between 2 and 6 weeks after enrollment/immunization. During the 1994 to 1995 season, patients were given 2 doses of influenza vaccine, separated by 3 weeks; endomyocardial biopsies and serologic studies were performed between 2 and 6 weeks after the second immunization or enrollment (if control subject). Biopsy results were evaluated with respect to vaccine response, immunosuppressive regimens, and patient demographics. RESULTS: Eighteen patients were enrolled in the single vaccine trial and 10 in the booster vaccine trial. Four of 14 vaccine recipients had biopsy specimens consistent with International Society for Heart and Lung Transplantation grades 2 to 3A as compared with 1 of 14 control subjects (grade 2) (p = .326). All episodes of rejection in the vaccine recipients were asymptomatic and responded to a single course of treatment. Rejection was unrelated to the time from transplantation, doses of immunosuppression, age, or number of doses of or response to vaccine. CONCLUSIONS: Influenza vaccine can be safely administered to most heart transplant recipients but may be associated with low-level histologic rejection.     

Ureteritis and cholecystitis: two unusual manifestations of cytomegalovirus disease in renal transplant recipients

BACKGROUND: Common clinical manifestations of cytomegalovirus (CMV) infection include flu-like symptoms with fever, diarrhea, leukopenia, and elevated liver enzymes. Diagnosis is made by detection of the virus by buffy-coat blood culture or by polymerase chain reaction (PCR) analysis. METHODS: Here we describe two renal transplant recipients who presented with unusual manifestations of CMV disease (cholecystitis and ureteritis). In both patients, no symptoms or signs of systemic CMV infection were present, and they were thought to have other common causes for cholecystitis and ureteral obstruction. RESULTS: Retrospective analysis of peripheral blood by PCR analysis was positive for CMV DNA. Histologic examination of the resected gall bladder and stenotic ureteric segment showed CMV inclusions, confirmed subsequently by in situ hybridization. Thus, we report that CMV infection may present with acute cholecystitis or ureteral obstruction without its classical clinical symptoms. CONCLUSIONS: Because CMV infection is common in transplant patients, the atypical manifestations of CMV should be considered in the differential diagnosis of posttransplant complications. Detection of CMV DNA in the peripheral blood by PCR analysis may help identify these patients.     

Combining tabular, rule-based, and procedural knowledge in computer-based guidelines for childhood immunization

IMM/Serve is a computer program which implements the clinical guidelines for childhood immunization. IMM/Serve accepts as input a child's immunization history. It then indicates which vaccinations are due and which vaccinations should be scheduled next. The clinical guidelines for immunization are quite complex and are modified quite frequently. As a result, it is important that IMM/Serve's knowledge be represented in a format that facilitates the maintenance of that knowledge as the field evolves over time. To achieve this goal, IMM/Serve uses four representations for different parts of its knowledge base: (1) Immunization forecasting parameters that specify the minimum ages and wait-intervals for each dose are stored in tabular form. (2) The clinical logic that determines which set of forecasting parameters applies for a particular patient in each vaccine series is represented using if-then rules. (3) The temporal logic that combines dates, ages, and intervals to calculate recommended dates, is expressed procedurally. (4) The screening logic that checks each previous dose for validity is performed using a decision table that combines minimum ages and wait intervals with a small amount of clinical logic. A knowledge maintenance tool, IMM/Def, has been developed to help maintain the rule-based logic. The paper describes the design of IMM/Serve and the rationale and role of the different forms of knowledge used.     

Arachidonic acid metabolism: a primer for head and neck surgeons

The arachidonic acid metabolites, or eicosanoids, are a large series of lipid-derived mediators capable of producing a multitude of physiologic effects in the local environment. They play important roles in a variety of signaling pathways in endocrinology, immunology, and oncology. A significant body of work in this area has occurred in squamous cell carcinomas of the head and neck over the past 15 years. This review will attempt to familiarize the head and neck surgical oncologist with the basic biochemical steps in the formation of these compounds, newer developments in the field of eicosanoid biochemistry, and related experimental evidence of the roles of these substances in head and neck cancer.     

Validation of serum transthyretin (prealbumin) as a nutritional parameter in hemodialysis patients

Discoloring of glass due to ionizing radiation depends on the absorbed dose. The radiation-induced light attenuation in optical fibers may be used as a measure of the dose. In high-energy photon beams (6 MV X rays), a lead-doped silica fiber can be calibrated. A dosimeter based on an optical fiber was developed for applications in radiation therapy. The diameter of the mounted fiber is 0.25 mm, whereas the length depends on the sensitivity required. To demonstrate the applicability, a customized fiber device was used to determine scattered radiation close to the lens of the eye. Measurements were compared with TLDs (LiF) in an anthropomorphic phantom. The comparison with TLD measurements shows good agreement. In contrast to TLD, optical fibers provide immediate dose values, and the readout procedure is much easier. Owing to its small size and diameter, interesting invasive dose measurements are feasible.     

The development and testing of a new NiTi-SE-steel uprighting spring

The uprighting spring presented here consists of a combination of superelastic material which is connected with a steel were by means of a crimped connector. Pseudo-elastic areas of such a spring can be used well by combining superelastic material with steel. The uprighting spring presented here yields the following advantages: 1. The uprighting moment of the molar is between 10 and 20 N with a 40 degree tipping of molar.2. The uprighting springs exhibit a large plateau in the area of 8 to 15 Nmm depending on a bending-in of an alpha-bend. 3. An intrusive force of approximately 0.5 to 1.0 N can be produced by varying the alpha-bend. The preformed uprighting spring in combination with a cross tube can be affixed without any problems, because only the alpha-activation must be bent in. 5. Practically, a reactivation during uprighting is not required. 6. An enlargement of the alpha-moment to produce an intrusive force makes great demands on the anchoring element. For this reason, one must check in each individual case, if an anchoring segment displays the required stability. 7. By lengthening the SE material at the crimped connector, the alpha and beta-moments become smaller, as does the intrusive (extrusive) force applied to molars.     

Role of MR venography in the evaluation of deep venous thrombosis

INTRODUCTION: Oral NSAIDs cause acute gastric injury that resolves, despite continued administration, by a process known as adaptation. Little is known about the factors that influence this process. METHODS: Sixty-two healthy volunteers were given a 28-day course of either etodolac 300 mg b.d. (13 subjects), naproxen 500 mg b.d. (23), enteric-coated diclofenac (10) or effervescent diclofenac 50 mg b.d. (16). All subjects were gastroscoped before and on days 1, 7 and 28 during drug administration, to assess gastric mucosal damage using a modified Lanza scale. Subjects were then divided into three categories: those who adapted completely, those who adapted incompletely and those who showed no adaptation. The proportion of subjects in each group was compared with respect to age, gender, smoking, the presence of Helicobacter pylori, and the NSAID prescribed. RESULTS: Fifty-nine subjects (median age 25.0 years, range 18-70) developed initial gastric injury to NSAIDs of whom 42 adapted completely, 13 adapted incompletely and four showed no evidence of adaptation. The mean age of subjects was lower in those who adapted (26.8 +/- 9.8 years) than those who adapted incompletely (32.5 +/- 10.3 years) and those who did not adapt (42.0 +/- 15.7 years, P = 0.01). There was no evidence of gender influencing adaptation. Of 17 H. pylori-positive subjects, a higher proportion had incomplete adaptation, with only nine subjects adapting completely (53% vs. 81%, P = 0.04). Sixteen subjects were smokers, of whom a greater proportion showed no evidence of adaptation (19% vs. 2%, P = 0.03). A smaller proportion of those who took naproxen (48%) adapted completely than those who took enteric-coated diclofenac (89%), effervescent diclofenac (75%) or etodolac (91%, P = 0.03). CONCLUSION: Some adaptation occurred in over 90% of subjects after 4 weeks dosing with an NSAID, but adaptation was less frequent in older subjects and in smokers. Complete adaptation occurred less frequently in H. pylori-positive subjects and in those who were given naproxen.