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Biomedical subjects

D S Jackson

Publications and source records attributed to D S Jackson.

At least 19 recordsLinked to original sources

A kinetic study of the hydrolysis of the N-tosylalanine ester of 3-hydroxy-5-phenylpyrrole and related compounds by human leukocyte elastase.

The tosylalanine ester of 3-hydroxy-5-phenylpyrrole (HOPPy) is localized on reagent strips (Ames LEUKOSTIX) and used diagnostically to test urine for the presence of human leukocyte elastase (HLE) as an indication of urinary tract infection. We have determined the kinetic constants for the HLE-catalyzed hydrolysis of this substrate and the related substrates Tos-Ala-ONp, Cbz-Ala-OPPy, and Cbz-Ala-ONp, in solution at three different pH values. In the reagent strip matrix, diazo coupling of 4-diazo-3-hydroxy-1-napthylsulfonate (HONapN+2) with the enzymatic hydrolysis product HOPPy generates a purple color. We have also studied the kinetics of the reaction of HOPPy with HONapN+2 and other related diazonium salts such as 4-diazo-3-hydroxy-7-nitro-1-napthylsulfonate, 4-diazo-3-hydroxy-1,7-napthyldisulfonate, and 2-methoxy-4-(N-morpholinyl)benzene diazonium chloride. Tos-Ala-OPPy is the most reactive substrate among the compounds examined and kinetic studies indicate that deacylation is rate-limiting for HLE hydrolysis. The presence of decanol accelerates the enzymatic hydrolysis of Tos-Ala-OPPy with a kcat/KM = 10(7) M-1 s-1, which is close to the diffusion-controlled limit. For the diazo coupling reaction, the rate is affected by the substituents on the naphthalene ring and by the buffer in which the reaction occurs. This research has elucidated some important mechanistic features for the reaction of these compounds and may lead to improved methods for the detection of leukocyte elastase.

Alanine

Chymase-directed serine protease inhibitor that reacts with a single 30-kDa granzyme and blocks NK-mediated cytotoxicity.

Cytotoxic NK and T lymphocytes kill virally infected cells within minutes without causing damage to themselves or bystander cells. One mechanism of killing involves exocytosis of granules containing serine proteases and perforin. Serine protease inhibitors block killing of target cells mediated by the cytotoxic lymphocytes. There are at least five different serine protease activities in cytolytic granules. Ten different serine protease sequences have been identified with the use of cDNA-specific clones. It is not known whether only one or several of these serine proteases are essential for cytolytic activity. In this study we show that an irreversible serine protease inhibitor, biotinyl-Aca-Aca-Phe-Leu-PheP(OPh)2, selectively inhibits a chymotrypsin-like (chymase) serine protease activity of rat RNK-16 granule extracts. Under the same conditions, only one 30-kDa (reduced) band was detected on protein blots. Furthermore, only one of three chymase peaks separated by hydrophobic interaction chromatography was inhibited. When this granzyme was inhibited, granule-mediated lysis of erythrocytes was diminished. NK cell killing was completely blocked when biotinyl-Aca-Aca-Phe-Leu-PheP(OPh)2 was added to cytotoxicity assays at 200 microM with rat splenocytes as effectors. By confocal fluorescence microscopy, we show that this inhibitor localizes to distinct regions within RNK-16 cells and rat NK cells. Inhibitor treatment of intact cells inactivated the chymase activity and reduced lysis found in their dense organelles. Together these data indicate that biotinyl-Aca-Aca-Phe-Leu-PheP(OPh)2 inhibits a granule chymase that is essential to cytolytic activity of NK cells.

Amino Acid Sequence

Practical applications of element-specific detection by inductively coupled plasma atomic emission spectroscopy and inductively coupled plasma mass spectrometry to ion chromatography of foods.

Three practical examples are presented to demonstrate the utility of element-selective detection for ion chromatography (IC). The determination of As species in a liquid health food supplement by IC with inductively coupled plasma atomic emission spectroscopy (IC-ICP-AES) is shown to confirm results obtained for total As. IC-ICP-AES is also used to investigate the identity of an unknown peak in a sample of shrimp commercially treated with tripolyphosphate. Finally, results are presented for the determination of residual bromate in baked goods by IC with inductively coupled plasma mass spectrometry detection.

Animals

Polyorchidism: functional classification and management strategy.

Polyorchidism is rare. We report a recent case and review the literature. A simple classification based on anatomic and functional arrangements of the testes and their drainage systems is described. Combining this classification with a knowledge of potential complications, we propose a management strategy.

Adult

Knowledge and attitudes about cervical cancer and the Pap smear among 10th-grade girls.

Data from questionnaires completed by 419 10th-grade girls were analyzed as part of a school health education program. The questionnaire was designed to collect knowledge of, attitudes toward, and experiences with cancer and cancer prevention. Data were collected from randomly selected health classes preceding a presentation on breast and cervical cancer prevention. Results showed that the girls were pessimistic about chances of surviving cancer and did not differentiate survival by type or site of the cancer. Although there was considerable confusion about its purpose, 27.6% reported having had a Papanicolaou smear within the past year and 79.2% correctly identified the Pap smear as a test for cancer.

Adolescent

Cefadroxil kinetics and dynamics in a pediatric patient with acute osteomyelitis.

Cefadroxil has been used for the treatment of acute osteomyelitis. However, its pharmacokinetics and pharmacodynamics have not been studied in these patients. We evaluated the kinetics and dynamics of cefadroxil in a pediatric patient with osteomyelitis caused by Staphylococcus aureus. After initial clinical improvement on intravenous nafcillin, the patient received oral cefadroxil, 60 mg/kg every 12 h. Blood samples were collected at 0, 1, 2, 4, 6, 8 and 12 h; bactericidal titers were determined at 2 and 12 h. Cefadroxil was measured by an HPLC method. The peak and trough serum concentration of cefadroxil was 35.4 and 0.5 micrograms/ml, respectively. The oral clearance and elimination half-life were 11.5 ml/min/kg and 2.4 h, respectively. The peak bactericidal titer was 1:4 and the trough titer was less than 1:2 for the infecting organism. The child's finger appeared worse with an increase in swelling and erythema after 2 days of cefadroxil therapy. Cefadroxil was discontinued and the patient was treated successfully with intravenous nafcillin. The apparent failure of cefadroxil therapy can be explained by lower than recommended peak (greater than or equal to 1:8) and trough (greater than or equal to 1:2) titers for therapeutic success. Thus, an alternative dosage regimen of cefadroxil should be considered in the future studies.

Cefadroxil

The use of ultrasound in the management of primary psoas abscess.

Whereas psoas abscess secondary to many local intra- and extra-peritoneal septic processes is well recognised, primary psoas abscess is much less common and the diagnosis is often delayed, leading to significant morbidity and mortality. A case of primary psoas abscess is described and the role of ultrasound in the investigation and management is discussed.

Abscess

Sigmoid volvulus in late pregnancy.

Sigmoid volvulus in late pregnancy is an uncommon complication. We report a case of a 35 year old Caucasian woman who presented with symptoms and signs of intestinal obstruction when 34 weeks pregnant. Surgical management of the case is described and the literature reviewed.

Adult

Sepsis in soft tissue limbs wounds in soldiers injured during the Falklands Campaign 1982.

The factors related to the development of sepsis in the soft tissue limb injuries sustained by soldiers during the Falklands Campaign have been assessed. Delay in surgery and delay in antibiotic administration are the most important factors, and where delay in surgery is inevitable, delay in antibiotic administration assumes an even greater importance.

Anti-Bacterial Agents

Prospective randomized multicentre trial of proximal gastric vagotomy or truncal vagotomy and antrectomy for chronic duodenal ulcer: results after 5-7 years.

In a prospective, randomized study 145 patients with duodenal ulcer have been followed 5-7 years after proximal gastric vagotomy (PGV) or truncal vagotomy with antrectomy (TVA). Postoperative complications were significantly higher after TVA (P less than 0.0005). There was one death due to anastomotic leakage after TVA. The recurrence rate was significantly higher after PGV (9.9 per cent). Postoperative symptoms were less after PGV (P less than 0.01). Due to the recurrence rate after PGV there was no overall significant difference in the Visick grading, although perfect results (Visick I) were seen significantly more often (P less than 0.01). It is concluded that better results follow PGV.

Body Weight