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K Walker

Publications and source records attributed to K Walker.

At least 19 recordsLinked to original sources

Tumor markers CA 19-9 and CA 195 are also useful as markers for cystic fibrosis.

When monoclonal kits are used we can no longer detect highly elevated serum concentrations of carcinoembryonic antigen in cystic fibrosis (CF) patients as we could earlier (Pediatr Res 10:223-236, 1975). Instead, we find increased concentrations of CA 19-9 or CA 195 in the CF sera. The serum levels of CA 19-9 not only reflect the pulmonary condition of CF patients but also respond well to antibiotic therapy. Several lines of evidence suggest that the elevated serum concentration of CA 19-9 is derived from sputum and corresponds with the amount of sputum in the lung. Correlations between CA 19-9 and CA 195 in random and serial specimens from both patients with CF and patients with pancreatic carcinoma suggest that all sera contain heterogeneous, Lewis blood group-related epitopes and the proportions of various epitopes are different among individual patients. When monitored on multiple tumor markers, the pattern of CF is different from that of pancreatic carcinoma although both usually show elevated CA 19-9. Our study indicates that both CA 19-9 and CA 195 can be used as sensitive markers for the early detection of exacerbation in CF patients.

Adolescent

Changes in the CA 19-9 antigen and Lewis blood group with pulmonary disease severity in cystic fibrosis.

The altered carbohydrate structure of sputum from patients with cystic fibrosis (CF) has been thought to be due to the inflammatory airway response. Carcinoembryonic antigen (CEA) and CA 19-9 detect sialosylated carbohydrates in mucus. The epitope of CA 19-9 is part of the Lewis A (Le(a)) blood group antigen. Serum concentrations of CEA and CA 19-9 were determined by radioimmunoassay in 41 CF patients, aged 6-34 years; 16 were asymptomatic Outpatients, and 25 had been admitted for pulmonary exacerbations. There was no difference in CEA between groups. The CA 19-9 serum concentration was elevated in 90% of patients who had at least one of the two Lewis antigens. The CA 19-9 concentration of Inpatients with exacerbations was 2.7 times that of stable Outpatients (263 +/- 44 versus 99 +/- 13 U/mL; P less than 0.02). CA 19-9 correlated significantly with age (r = 0.35, P less than 0.05), Brasfield score (r = 0.39, P less than 0.015), pulmonary function tests, cough severity (r = 0.50, P less than 0.001) and NIH clinical score (r = 0.57, P less than 0.001). CA 19-9 concentration of Inpatients decreased by 44% from admission to discharge (302 +/- 45 to 169 +/- 39, P less than 0.02). Fourteen of 25 (56%) of the Inpatients were Le(a) positive versus only 3/15 (20%) of Outpatients who had milder lung disease (P less than 0.002). Of the Inpatients, 25% with more advanced lung disease were Le(a+b+), a rare blood group in the normal population, and one not observed in the Outpatients with milder disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

A nationwide quality assurance program can describe standards for the practice of pathology and laboratory medicine.

An important component of quality assessment is the analysis of peer group comparisons, although little data are available for evaluation. We developed and tested six interinstitutional quality indicators related to Pathology and Laboratory Medicine among 36 institutions. Results showed that the mean frequency of intraoperative frozen section consultations (6.0%), sensitivity of fine needle aspiration cytology diagnosis (87%), nosocomial infections (5.0%) and average cross-match to transfusion ratio (2.1%) was comparable with previous studies, but the range of values was large. The median stat laboratory turnaround time of approximately 1 hr for CSF cell count, glucose, protein and gram smear was considerably longer than expected from previous investigations, and was longer for larger institutions. Analysis of serious laboratory reporting errors showed the lowest number detected by individuals working in transfusion medicine, and highest numbers among hematology workers. We conclude that interinstitutional comparison of data from quality assurance programs can be used to describe performance standards related to the quality and effectiveness of care.

Biopsy, Needle

Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element.

It has been reported recently that the wild-type p53 gene product can positively regulate the expression of a test gene adjacent to the enhancer-promoter elements of the murine muscle-specific creatine kinase (MCK) gene. This discussion reports the identification of a wild-type p53 protein-specific DNA-binding element located within the p53-responsive region of the MCK enhancer-promoter element. This p53 protein/DNA-binding element has been defined by DNase I footprint analysis, which identified a 50-bp region. This 50-bp sequence was sufficient to confer wild-type p53 responsiveness on a heterologous minimal promoter. The mutant forms of p53 protein are much less capable of stimulating this DNA element. This study has identified the first example of a naturally occurring wild-type p53-specific DNA-binding element that is able to mediate positive regulation of a test gene. The results suggest a biological function in gene regulation for the wild-type p53 protein that is lost or altered in the mutant p53 proteins.

Animals

Indomethacin worsens and a leukotriene biosynthesis inhibitor accelerates mucosal healing in rat colitis.

The implication of leukotrienes as mediators of inflammation and recent evidence that prostaglandin analogues provide a beneficial effect during experimental colitis led to the speculation that (i) leukotrienes may be injurious and (ii) prostaglandins may be protective to colonic mucosa. Using a 2% acetic acid induced rat colitis model, we administered specific cyclooxygenase (indomethacin) and leukotriene biosynthesis inhibitors (MK-886) to examine the effect of endogenous prostaglandins and leukotrienes on colonic macroscopic injury, mucosal inflammation as measured by myeloperoxidase activity, net in vivo intestinal fluid absorption, and colonic PGE2 and LTB4 levels as measured by in vivo rectal dialysis. Indomethacin treatment prior to induction of colitis reduced endogenous mucosal PGE2 levels and exacerbated macroscopic ulceration and net fluid absorption. Addition of the exogenous PGE1 analogue misoprostol to the indomethacin-exacerbated colitis completely healed colonic macroscopic ulceration and inflammation but only partially improved fluid absorptive injury. The specific leukotriene biosynthesis inhibitor MK-886 administered prior to induction of colitis healed macroscopic ulceration and inflammation but not fluid absorptive injury. This mucosal reparative effect of MK-886 occurred at a dose that reduced colonic LTB4 synthesis while concomitantly enhancing PGE2 levels. Combining MK-886 with misoprostol treatment improved not only macroscopic ulceration and inflammation but also provided a synergistic effect that maintained net colonic fluid absorption at noncolitic control levels. These studies suggest that, during the induction of experimental colitis, endogenous prostaglandins play a pivotal role in providing a mucosal healing effect, and that leukotriene biosynthesis inhibitor may manifest part of its beneficial effect by shifting arachidonic acid metabolism towards production of prostaglandins.

Acetates

Two weeks of oral synthetic E2 prostaglandin (Enprostil) improves the intestinal morphological but not the absorptive response in the rat to abdominal irradiation.

Enprostil, a synthetic E2 prostaglandin, was administered in a dose of 5 micrograms/kg body weight by gastric tube to rats for 14 days following abdominal irradiation with a single dose of 600 cGy from a 137Cs source. Enprostil prevented the body weight loss and the reduced food intake observed in irradiated animals given placebo, and also prevented the irradiation-associated decline in the mucosal weight and surface area of the ileum. Enprostil given to nonirradiated animals reduced the maximal transport rate (Vmax) and the apparent Michaelis constant (Km*) for the ileal uptake of D-glucose, but did not prevent the irradiation-associated decline in the ileal uptake of glucose. Thus, there is a dissociation of the effects of Enprostil on the morphological and the absorptive properties of the intestine. It is concluded that a 2-week course of a daily oral dose of E2 prostaglandin begun shortly after a single exposure to nonlethal abdominal irradiation prevents the radiation-associated reduction in the intestinal mucosal surface area and the animal's body weight, but does not prevent the malabsorption of glucose.

Animals

Malignant melanoma in a Hispanic male with nevus of Ota.

Nevus of Ota is uncommon in the non-Oriental population. We report a case of malignant melanoma with metastasis to the genitourinary tract in a Hispanic male with nevus of Ota. Thirty-six prior cases of nevus of Ota with malignant melanoma reported in the English language are reviewed. Sixty-eight percent were women; 76% were Caucasians. Metastatic disease was reported in 16%. Three patients had liver metastases. Our case was the first involving the genitourinary tract. All but one patient with metastatic disease died within 1 month of presentation. Despite the increased frequency of nevus of Ota in the Japanese, only 4 cases of malignant melanoma have been reported. Nevus of Ota would appear to be a risk factor for developing malignant melanoma in the Caucasian population.

Brain Neoplasms

Verapamil alters eicosanoid synthesis and accelerates healing during experimental colitis in rats.

In inflammatory bowel disease, prostaglandins are mucosal protective whereas leukotrienes are proinflammatory. Recent evidence suggests that the formation and action of leukotrienes are calcium-dependent, whereas the formation and action of prostaglandins are not. To examine the possibility that, because of differential regulation of arachidonic acid metabolism, calcium channel blockade might alter mucosal eicosanoid synthesis and accelerate healing during inflammatory bowel disease, we treated a 4% acetic acid-induced colitis model with verapamil and/or misoprostol and determined the effects on colonic macroscopic injury, mucosal inflammation as measured by myeloperoxidase activity, in vivo intestinal fluid absorption, and mucosal prostaglandin E2 and leukotriene B4 (LTB4) levels as measured by in vivo rectal dialysis. In colitic animals, verapamil treatment significantly improved colonic fluid absorption and macroscopic ulceration. This mucosal-protective effect of verapamil occurred in the presence of a twofold reduction in mucosal LTB4 synthesis. In noncolitic animals, verapamil alone had no effect on in vivo fluid absorption, macroscopic ulceration, or myeloperoxidase activity but did induce a threefold reduction in LTB4 synthesis in addition to shifting arachidonic acid metabolism towards a sixfold stimulation of prostaglandin E2 synthesis. Our results show that, when administered before the experimental induction of colitis, the calcium channel blocker, verapamil, has a mucosal-protective effect that occurs as a consequence of reduced mucosal leukotriene synthesis and increased prostaglandin synthesis. This differential regulation of arachidonic acid metabolism may play an important role in the development of novel therapeutic agents for inflammatory bowel disease.

Animals

Treatment of gastric lymphoma.

A review of 52 patients with gastric lymphoma at the Texas A&M University College of Medicine Affiliated Scott and White Memorial Hospital (Temple, TX). was performed to determine the influence of different treatment modalities. Thirty-one patients had a potentially curative resection, while 21 underwent a palliative procedure or biopsy alone. Overall 5-year survival was 73.4 per cent after curative resection and 38.3 per cent for lesser operative procedures (P less than .005). Adjuvant radiation was given to 14 patients after curative resection with a 5-year survival rate of 71.5 per cent compared to 82.4 per cent in the 17 patients treated by curative resection alone (nonsignificant). Patients who underwent palliative surgery or biopsy who received postoperative radiation therapy had a 38.0 per cent 5-year survival rate compared to a 0.0 per cent 5-year survival rate in patients who received no therapy (P = .18). The authors conclude that curative resection is the treatment of choice for gastric lymphoma, but radiation therapy may offer some benefit when complete resection is not feasible.

Actuarial Analysis

Quantification of errors in laboratory reports. A quality improvement study of the College of American Pathologists' Q-Probes program.

Over a 3-month period, 61,496 errors were detected in clinical laboratory reports by 631 participants in the College of American Pathologists' 1990 Q-Probes program. Each error detected was defined as an opportunity for improvement. Almost 4% of the detected errors were attributed to nonlaboratory personnel and approximately 4% (A errors) had a major impact on patient care. Rates of B (serious errors, but unlikely to affect patient care) and C errors (minor clerical errors) were approximately equal. When expressed in terms of measures of laboratory work loads, four of six measures of mean errors were lowest in blood banking, intermediate in chemistry and microbiology, and highest in hematology. Thirteen percent of participants did not have an error detection system in place. We conclude that many errors go undetected, and we recommend that an effective system for error detection in patient reports should be employed in all laboratories.

Blood Banks

Inhibition of protein synthesis by anti-5.8 S rRNA oligodeoxyribonucleotides.

To examine the role of the 5.8 S rRNA in ribosome function, oligodeoxyribonucleotides, complementary to chemically accessible sequences, were incubated with rabbit reticulocyte or wheat germ extracts undergoing protein synthesis in vitro. Significant and reproducible inhibitions were observed with several different oligonucleotides, the most inhibitory being specific for the universally conserved GAAC sequence. Mutant or heterologous sequences were substantially less inhibitory, results which clearly implicate the 5.8 S rRNA in the inhibitory process and are consistent with the possibility that the 5.8 S rRNA plays an important role in the binding of tRNA.

Animals

Termination region in rRNA genes from a eucaryotic thermophile, Thermomyces lanuginosus.

S1 mapping of the termination region in the ribosomal DNA from a thermophilic fungus, Thermomyces lanuginosus, revealed three distinct termini corresponding to the mature 25S rRNA, a precursor that is 19 nucleotides longer and corresponds to the 37S precursor in yeast cells, and a putative termination site at +96 that bears a limited sequence homology with the SalI box of mammalian cells. An estimate of the secondary structure suggested that the three termini are in close proximity, a feature that may be essential to precursor termination and maturation. The results raise questions regarding recently reported relationships between ribosomal DNA termination and spacer enhancer elements in fungi.

Base Sequence

XO/XY mosaicism in phenotypic males.

Eight cases of 45 XO/46 XY mosaicism are described: four were phenotypic males. Karyotyping should be performed more frequently in short boys as growth hormone treatment and testicular biopsy, to screen for carcinoma in situ, are likely to be beneficial.

Adolescent

Radiation and the small intestine. Future perspectives for preventive therapy.

Radiotherapy continues to enjoy a prominent role in the treatment of certain human tumors. Unfortunately, the undesired effect of radiation upon normal intestinal tissue often limits its therapeutic potential. While there is abundant information on the effects of radiation on the morphology of the intestine and on the proliferative process which occurs in the intestinal crypts, there is a paucity of information on the early and late effects of sublethal doses of radiation upon the absorptive functions of the intestine. The intestinal epithelium has a rapid turnover rate and is highly radiosensitive. Radiotherapy for malignant human neoplasms is a relatively safe and effective form of treatment, but it may become limited by its undesired side effects upon the gastrointestinal tract. A variety of clinical tests have been suggested as potential indicators of impending intestinal damage, but there is little information on the time course of radiation damage and the associated impairment of intestinal function. Such basic information is essential to assess early functional changes and to thereby allow for the development of suitable clinical tests to allow for the prediction of impending intestinal damage. Provision of this information to the radiotherapist would permit alterations to the timing or dose schedules of radiotherapy and would allow continued treatment, while avoiding or reducing unwanted side effects. In recent years, there has been extensive research on radiation injury to small intestine. This article will review some of the progress in this field, and will focus on potential future therapy to prevent or treat radiation damage to the intestine. These agents include WR-2721, enprostil, vasopressin, defined-formula diets and alterations in the ratio of dietary polyunsaturated-saturated fatty acids.

Forecasting

Changes in mallard (Anas platyrhynchos) serum chemistry due to age, sex, and reproductive condition.

Selected serum constituents were analyzed from 50 adult mallards (Anas platyrhynchos) of both sexes during several stages of reproduction: pre-egg laying, egg laying, incubating, molting, and postreproductive. Similar assays were conducted on sera from ducklings aged 5 to 58 days. Values for total protein (TPR), albumin (ALB), glucose (GLU), gamma-glutamyl transferase (GGT), calcium (CA), phosphorus (PHOS) and magnesium (MG) differed by sex. When all data were combined and analyzed for sex-related differences within each reproductive condition separately, all assays except lactate dehydrogenase (LD-L), cholinesterase (CHE), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CRN) and direct bilirubin (BIDI) differed between sexes during one or more reproductive periods. Each assay showed differences among the various reproductive conditions regardless of gender. The pattern of change differed between sexes. All assays except ALB, GLU, CA and MG showed age-related changes. Lipemia in the sample interfered with all chemistries except TPR, LD-L and CA. Results indicate that when using clinical chemistry as a diagnostic tool in the mallard, age and reproductive condition should be determined in order to compare the data to appropriate control values.

Age Factors