Effects of adenosine, ATP, and UTP on chloride secretion by epithelia explanted from fetal rat lung

To determine the role of intensive chemotherapy and allogeneic bone marrow transplantation (BMT) in treatment of refractory anemia with excess of blasts (RAEB) or RAEB-t (in transformation), the outcome of 37 consecutive children, 12 with RAEB and 25 with RAEB-t, diagnosed between 1985 and 1995 was analyzed. Fourteen patients received intensive chemotherapy according to the AML-BFM protocols 83, 87, or 93 (group 1). Seven patients were treated less intensively with the 6-week consolidation phase as induction (group 2). Allogeneic BMT was performed in 10 children of group 1 and 2 after, and in eight (group 3) without prior chemotherapy. Eight children received minimal or no chemotherapy (group 4). Of 21 children (groups 1 and 2) 17 (81%) achieved complete or partial remission after chemotherapy, 12 of them (10 of group 1) remained in remission, eight after BMT. Five-year survival in 29 children treated intensively (groups 1-3) was 46%, SE 12%. Two of the other eight children (group 4) remained alive, one after spontaneous remission. Outcome after BMT was related to the blast count in the bone marrow prior to BMT. None of 10 children (including two with minimal or no chemotherapy) with < or = 12% blasts before BMT relapsed, in contrast to five of eight patients with a higher blast count (P log rank 0.02). We conclude that a substantial number of children with RAEB or RAEB-t can achieve remission with intensive AML-specific chemotherapy. In patients responding to intensive chemotherapy an increase in long-term survival after allogeneic BMT can be expected.     

Spontaneous loss of viral episomes accompanying Epstein-Barr virus reactivation in a Burkitt's lymphoma cell line

Life-long viral persistence is a hallmark of human herpesvirus infection. In the Epstein-Barr virus (EBV)-positive Burkitt's lymphoma (BL) cell line, Mutu, spontaneous loss of all viral episomes accompanied productive viral DNA replication. The molecular configuration of intracellular EBV DNA evolved from monoclonal episomes in cells retaining the original tumor phenotype to predominantly replicating linear DNA and, subsequently, only integrated forms in BL cells that had acquired the lymphoblastoid cell phenotype. Transient appearance of deleted, rearranged WZhet EBV DNA capable of disrupting viral latency, along with the integration of viral DNA into human chromosomes, indicates a genetic instability in the host cell which, if duplicated in vivo, may affect configuration and persistence of the viral genome in expanding malignant cell clones.     

The clinical relevance of the Waterlow pressure sore risk scale in the ICU

OBJECTIVE: To evaluate whether the Waterlow pressure sore risk (PSR) scale has prognostic significance for intensive care patients. DESIGN: A prospective study. SETTING: The surgical intensive care unit (ICU) of the University Hospital Rotterdam. PATIENTS: Data were evaluated from 594 patients who had been admitted to the ICU during the year 1994. METHODS AND RESULTS: Each patient was assessed daily with respect to their Waterlow PSR score and the development of pressure sores in the sacral region. Actuarial statistical methods were used to analyse the predictive value of the risk score. When a patient had a Waterlow PSR score > 25 on admission, the risk of developing a pressure sore was significantly increased compared to patients with a PSR score < 25. After admission, the daily Waterlow PSR scores obtained were significantly associated with the risk of developing a pressure sore. For each additional point this risk increased by 23% (95% confidence interval 17 to 28%). CONCLUSIONS: The Waterlow PSR scale provides the medical and nursing staff at an early stage with reliable information about the risk patients have in developing a pressure sore.     

A review of new oncotropic tracers for PET imaging

We have developed three biochemical probes to determine if they are sensitive probes of early biochemical change in a tumor. All three probes appear to have the appropriate properties for in vivo imaging, but must now be evaluated as probes for the sensitive detection of changes in early malignant disease.     

A study of afferent input to the inferior olivary complex in the rat by retrograde axonal transport of horseradish peroxidase

The multilamellate glial sheath of mixed nerve roots of the sixth abdominal ganglion of crayfish contains numerous hemi-desmosomes which appear to attach glial lamellae to material in adjacent extracellular clefts. These junctions, which have been described in detail in an earlier report (Shivers and Brightman, '76), are irregular in shape, punctuate and may be as large as 1 mum in diameter. Surgical interruption of sixth ganglion nerve roots results in regeneration of motor axons and their multilamellate glial sheaths. As the glial processes grow and re-establish a highly organized axon sheath, hemi-desmosomes appear. These junctions are present at the advancing edge of glial processes as well as on their lateral margins. Developing hemi-desmosomes are characterized as a diffuse aggregation of 120-130 A intramembrane particles which are present three weeks following nerve section. As growth and reorganization of the sheath proceeds, the intramembrane particles appear to aggregate and form irregular clusters of varying dimensions. Regenerating nerves freeze-cleaved 8 to 16 weeks following surgery exhibit junctional particle aggregates similar to those in normal unoperated nerve roots. Origin of the intramembrane particles which comprise the junctional aggregated in unknown. Perhaps they are synthesized de novo by the regenerating glial cells or, they may be remnants of complexes which became dispersed following surgery. This is the first report of a freeze-fracture study of hemi-desmosome plasticity in an invertebrate nervous system.     

Conversion of proparathyroid hormone to parathyroid hormone: studies in vitro with trypsin

The conversion of proparathyroid hormone to parathyroid hormone (PTH) was studied in vitro employing pancreatic trypsin as a prototype converting enzyme. Digestion of intact radiolabeled bovine prohormone with trypsin (0.1%) (w/w) resulted in release of a peptide comigrating with intact hormone marker in systems resolving both on the basis of charge (urea polyacrylamide gels, pH 4.4) and size (sodium dodecyl sulfate-urea polyacrylamide gels, pH 7.2). Tryptic digestions of a synthetic analogue of bovine prohormone, ProPTH-(-6 + 34), consisting of the prohormone hexapeptide covalently bonded to the NIH2 terminus of the active fragment of the hormone, released in high yield the hexapeptide and the intact active hormone fragment before any other smaller fragments. Analyses of digestions were by: (i) thin-layer chromatography and amino acid analysis of digestion products; (ii) comparison of the biological activity of the prophormone substrate and the products of digestion; and (iii) peptide end-group analysis by the Edman method during progressive tryptic hydrolysis over 22 h. The latter experiments demonstrated cleavage of more than 75% of the hexapeptide-hormone peptide bond before cleavage of other trypsin-sensitive sites within the molecule. It is concluded that the specificity of cleavage at the hexapeptide-hormone bond in the process of intracellular hydrolysis of proparathyroid hormone resides primarily in the sequence and/or conformation of the precursor molecule; inasmuch as conversion of prohormone to hormone can be efficiently accomplished by pancreatic trypsin in vitro, there is, therefore, no need to postulate the existence of an intracellular converting enzyme within the parathyroid cell that possesses unique hydrolytic specificity.     

Pyogenic arthritis of the sacro-iliac joint. Long-term follow-up

Nine cases of sacro-iliac pyarthrosis are presented. The difficulty in localizing the infection is attributable mostly to failure to appreciate the posteriorly situated physical findings. This, and the difficulty with early roentgenographic demonstration of the lesion, may lead to unnecessary abdominal exploration (as in two of our patients) or to prolonged delay in diagnosis and hence spread of the infection. Awareness of the usual physical findings and prompt use of radioisotope scanning to localize the infection led to earlier diagnosis and avoidance of surgery in three patients seen recently. Antibiotic therapy, with or without surgery, led to cure in all patients, with minimum sequelae.