Staurosporine and its derivatives enhance f-Met-Leu-Phe-induced superoxide production via phospholipase D activation in human polymorphonuclear leukocytes

Staurosporine (STAR) is one of the most potent inhibitors of protein kinase C (PKC). It is known that in human polymorphonuclear leukocytes (PMNs), the phorbol ester-induced generation of superoxide anion (respiratory burst) is effectively inhibited by STAR in a dose-dependent manner, whereas superoxide generation induced by chemoattractants, e.g. n-formyl-methionyl-leucyl-phenylalanine (FMLP) or PAF, is regulated biphasically by STAR. We compared the effects of STAR and K252a on FMLP-induced superoxide production from PMNs and examined the effects of propranolol, a inhibitor of phosphatidic acid (PA) phosphohydrolase, on the potentiation of the production by STAR. We also examined the effects of some derivatives of STAR and K252a on the production and the alteration of the effects induced by propranolol pretreatment. When PMNs were stimulated with FMLP, STAR potentiated superoxide production by 240.5 +/- 30.9% at a low concentration (100 nmol/l). Propranolol pretreatment specifically inhibited the potentiation. When phorbol-12-myristate-13-acetate (PMA) was used as a stimulant, STAR inhibited superoxide production dose-dependently and did not enhance the production. K252a inhibited PMA or FMLP-induced superoxide production dose-dependently and did not enhance FMLP-induced superoxide production. STAR derivatives showed potentiation of FMLP-induced superoxide production similar to that of STAR at concentrations ranging from 10-100 nmol/l, and propranolol (200 mumol/l) effectively inhibited it. K252a derivative NA332 did not show any potentiative effect on the production. PMA-induced superoxide production was inhibited by all compounds dose-dependently.(ABSTRACT TRUNCATED AT 250 WORDS)     

Longitudinal bone mineral density changes in early rheumatoid arthritis

A prospective longitudinal study of patients with early RA was performed to examine the influence of disease duration, disease activity and physical activity on bone loss. Sixty-seven patients with non-steroid treated RA of less than 5 yr duration, including 16 patients with disease duration less than 6 months, had BMD measurements of the femoral neck and the lumbar spine over a 12-month period using dual energy X-ray absorptiometry. The BMD changes were compared with values from 72 control patients and were also correlated with serial measurements of disease activity (measured by the Stoke Index) and disability [measured by the Health Assessment Questionnaire (HAQ) score], at 3-monthly intervals over the 12-month period. No significant differences in BMD changes were found between RA patients and controls overall. Patients with disease duration of less than 6 months had significantly greater loss of BMD at the femoral neck (-3.9%, S.E.M. 1.5) than the remainder of the cohort (-0.2%, S.E.M. 0.7) (P = 0.02) and controls (-0.8%, S.E.M. 0.6). Lumbar spine BMD changes correlated with the initial Stoke Index (Rs-0.373, P = 0.01) but not mean Stoke Indices. There was no correlation of BMD changes with age or HAQ scores. These findings suggest that significant bone loss occurs within the first few months of disease in patients with RA.     

Evidence for superantigen involvement in insulin-dependent diabetes mellitus aetiology

Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease whose onset is believed to be triggered by unknown environmental factors acting on a predisposing genetic background. Islet-infiltrating T (IIT) cells from two IDDM patients, who had died at the onset of the disease from brain swelling as a complication of ketoacidosis, were analysed. The results provided evidence for the involvement of a pancreatic islet cell membrane-bound superantigen as a diabetes aetiopathogenetic factor. There was a selective expansion of a T-cell receptor (TCR) variable segment of the beta-chain (V beta 7) in these IIT cells in association with unselected V alpha-chain segments; extensive junctional diversity of the TCR V beta 7 chains; and evidence of positive selection, after exposure to diabetic islet cell membrane preparations, of V beta 7+ T-cell clones among peripheral blood lymphocytes from non-diabetic individuals.     

Ventilatory response to severe acute hypoxia in guinea-pigs and rats with high hemoglobin-oxygen affinity induced by cyanate

Laparoscopic pelvic lymph node dissection has been applied as a minimally invasive staging technique for men with prostate cancer. This procedure has been shown to shorten markedly postoperative hospitalization, decrease analgesic requirements and shorten convalescence period compared to open pelvic node dissection. However, the laparoscopic procedure takes longer to perform and many disposable instruments are used, thus increasing the cost. We determine the overall cost of laparoscopic versus open pelvic lymph node dissection. Between January 1989 and April 1992, 61 men underwent only staging pelvic lymph node dissection for cancer of the prostate at a single university teaching hospital. Of these patients 11 and 50 underwent open and laparoscopic pelvic lymph node dissection, respectively. Information from the hospital business office was reorganized into preoperative, intraoperative and postoperative expenses. All individual charges were transformed up or down to the dollar amounts of the 1990 to 1991 fiscal year so as to correct for inflationary changes. Preoperative costs were not significantly different between the 2 operative approaches. Intraoperative expenses were 52% greater if laparoscopic pelvic lymph node dissection was performed and can be explained by the longer operative times and use of disposable instrumentation. However, the postoperative period lasted an average of 1.61 days following laparoscopic pelvic lymph node dissection. Postoperative nursing and analgesic requirements were significantly more for patients undergoing open pelvic lymph node dissection. The overall postoperative costs following open pelvic lymph node dissection were 280% more expensive than for the laparoscopic procedure. The overall total costs were approximately $1,250 more for laparoscopic pelvic lymph node dissection. Wages lost or earned during this period and rapid return to normal activity following laparoscopic pelvic lymph node dissection would, in our opinion, justify this additional cost.     

Comparative analysis of HIV-1 and HIV-2 indeterminate western blot patterns

A comparison of HIV-1 and HIV-2 indeterminate Western blot patterns of Ghanaian sera collected between 1989 and 1990 was made. Antibodies to group specific antigen (GAG) gene products were most frequently detected both HIV-1 and HIV-2 indeterminate sera. HIV-2 GAG gene product p26 was shown to be a non-specific indicator of infection. Antibody to gp120, and envelope gene product of HIV-1 never occurred in indeterminate sera whereas antibodies to all the envelope gene products of HIV-2 were detected in indeterminate sera.     

Simplified method for the measurement of segmental colonic transit time

Segmental colonic transit has been measured in 101 patients. Two MBq of 111Indium absorbed on resin pellets and encapsulated in an enteric coated capsule was given at 7 00 am. Hourly images during the first day, and three images during each subsequent day were acquired for up to three days. Using all scan and patient data the scans were categorised in one of the five patterns of colonic transit: normal, rapid, right delay, left delay, or generalised delay. The geometric centres and per cent activity at each time point was compared between the five groups of colonic transit patients to find the best time for imaging and so to distinguish the five groups. During the first day, early images did not help in diagnosis of patterns of transit, however, in the later images (six hours onwards after the ingestion of the activity) the rapid transit groups could be identified. Images at 27 and 51 hours were both required to distinguish all five groups of patients from each other. Only in the 'normal' transit patients was there some excretion of the activity during the course of the second day, otherwise there was no difference in the images taken in the course of a day (second or third day). A simplified protocol requires a minimum of three images to distinguish all five patterns of colonic transit. The activity should be ingested in the morning (7 00 am) and the first image taken at the end of the working day (8-10 hours after ingestion), the second image on the morning of the second day, and the third image during the course of the third day. This simple protocol would provide all the clinically relevant information necessary for correct classification of the colonic transit.