A monoclonal antibody selected for probing the folding of staphylococcal nuclease and its N-terminal fragments

PURPOSE: Nitric oxide (NO) is generated in mammalian tissue by the conversion of L-arginine to L-citrulline. The reaction is catalyzed by nitric oxide synthase (NOS). NO has been suggested to have a dual role in tumor biology with both antitumor and tumor promoter activity. Furthermore, it has been proposed that NO contributes to interleukin-2-induced antitumor activity. Since interleukin-2 is used in the treatment of renal cell carcinoma (RCC) it was of interest to study the NOS activity in the human kidney and in RCC and its correlation to tumor grade. Furthermore, the effect of cytokine treatment on NOS activity and the effect of NO donor application was studied in cultured cells. MATERIALS AND METHODS: The effect of cytokine treatment on NOS activity and the effect of NO donor application on cell proliferation was studied in cultured human proximal tubular cells and in RCC cell lines HN4 and HN51. NOS activity was measured by the L-arginine to L-citrulline conversion assay. RESULTS: Calcium-dependent NOS activity was found in all non-malignant kidney tissues (486+/-63 pmol. min(-1) g(-1) tissue). The activity was significantly lower in RCC (24+/-6 pmol. min(-1) g(-1) tissue) and correlated with tumor grade; thus high grade tumors showed lower activity than low grade tumors. Calcium-independent NOS activity was not detected in non-malignant kidney tissue or in RCC tissue. In cultured proximal tubular cells and RCC cell lines HN4 and HN51, cytokine treatment induced a marked increase in NOS activity and NO exerted cytostatic effects on these cell lines. Conclusions: The NOS activity was higher in non-malignant kidney tissue than in RCC tissue and was inversely correlated with tumor grade. Furthermore, cytokine treatment induced a marked increase in NOS activity and NO exerted cytostatic effects on cultured proximal tubular cells and RCC cell lines.     

TraceLink: a model of amnesia and consolidation of memory

This investigation examined the feasibility of applying the conductance catheter technique for measurement of absolute aortic segmental volume. Aortic segment volume was estimated simultaneously in vitro by using the conductance catheter technique and sonomicrometer crystals. Experiments were performed in five isolated canine aortas. Vessel diameter and pressure were altered, as were the conductive properties of the surrounding medium. In addition, a three-dimensional finite-element model of the vessel and apparatus was developed to examine the electric field and parallel conductance volume under different experimental conditions. The results indicated that in the absence of parallel conductance volume, the conductance catheter technique predicted absolute changes in segmental volumes and segmental pressure-volume relationships that agreed closely with those determined by sonomicrometry. The introduction of parallel conductance volume added a significant offset error to measurements of volume made with the conductance catheter that were nonlinearly related to the conductive properties of the surrounding medium. The finite-element model was able to predict measured resistance and parallel conductance volume, which correlated strongly with those measured in vitro. The results imply that absolute segmental volume and distensibility may be determined only if the parallel conductance volume is known. If the offset volume is not known precisely, the conductance catheter technique may still be applied to measure absolute changes in aortic segmental volume and compliance.     

Amifostine (WR-2721) shortens the engraftment period of 4-hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support

4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty-three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high-dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.     

Developing visiting surgical services for rural and remote Australian communities

The University Department of Surgery at Queen Elizabeth II Medical Centre (Perth, Western Australia) has undertaken a pilot project to provide surgical services to country communities where no such service exists. Three surgeons undertake a regular schedule of appointments, and are accompanied by final-year medical students to give them experience with common conditions rarely managed in teaching hospitals. The service is supported by a central administrative office and coordinated by a general practitioner, who negotiates with the regional healthcare providers. Patients are referred by their general practitioner, who may work with the surgeon as anaesthetist or surgical assistant.     

Traumatic myocardial infarction caused by lead shot

The authors report the case of a 32 year old woman who was shot with a shotgun. Acute inferior wall infarction was detected fortuitously on electrocardiography and coronary angiography showed occlusion of the right coronary artery with lead shot. The single coronary lesion, absence, of other cardiac complications (haemopericardium, cardiac perforation, ...) and the favourable outcome with conservative medical treatment has not been previously reported to the authors' knowledge.     

Helicobacter pylori and gastric lymphoma]

BACKGROUND: Continent urinary diversion may be necessary in a range of urological abnormalities. In circumstances where the standard techniques are not possible, alternative innovative techniques may be used. METHODS: In a female patient with bladder exstrophy, a continent diversion was recommended. The appendix was not available, the ureters were not suitable and a continent stoma was fashioned from an isolated segment of colon. RESULTS: The stoma proved to be continent, although it was somewhat stenotic. However, clean intermittent catheterization maintained its patency. CONCLUSIONS: A continent catheterizable stoma may be constructed from a segment of colon. The technique may be considered when other well recognized methods are not feasible.     

Maximum cardiac output during incremental exercise by first-pass radionuclide ventriculography

A flow injection hydride atomic absorption spectrometric (FI-HAAS) method was developed for determining selenium in human milk and whole blood after microwave digestion of the sample. The sample (2 mL human milk or 0.25 mL blood) was introduced into the microwave vessel with 1.5 mL HNO3 and 0.25 mL H2O2 and 300 W (4 min) and 600 W (4 min) were applied. The digestion was completed by heating to 140 degrees C (2-3 h). Se (VI) was reduced to Se (IV) with hydrochloric acid. The instrumental conditions for FI-HAAS (concentrations of reducing agent and carrier acid, flow rate of argon carrier gas, and sample volume injected) were optimized. The detection limit of the proposed method was 0.23 ng/mL (assay) or 115 pg Se (absolute) in biological samples (1.15 ng/mL milk, 10.4 ng/mL blood). The precision values were 5.0% for milk and 4.0% for blood. The accuracy was evaluated with 2 reference materials, National Institute of Standards and Technology Non-Fat Milk Powder (found: 104.3 +/- 7.2 ng/g, certified: 110 +/- 10 ng/g) and Whole Blood Seronorm (found: 81 +/- 7.3 ng/mL, reference: 83 +/- 4 ng/mL). The results show the suitability of the method for selenium determination in human milk and whole blood. The method was applied to whole blood samples obtained from pregnant women and to human milk.     

Perceived equity and intimacy in marriage

The extent to which perceived inequity is related to perceived marital intimacy was examined. Sixty-six couples married five years or less were randomly selected from marriage license records in a western rural community. Equity/inequity was assessed using the Walster global measure of equity. Levels of overall intimacy, conflict resolution, affection, cohesion, sexuality, identity, compatibility, autonomy, and expressiveness were measured using the Waring Intimacy Questionnaire (WIQ). Inequity was associated with lower levels of overall intimacy, compatibility, identity, and expressiveness among the wives. Among the husbands, inequity was not associated with any types of intimacy. When comparing husbands in inequitable relationships to wives in inequitable relationships, the wives reported lower scores for only one kind of intimacy--identity. Explanations and implications for marriage therapy are discussed.