Danazol for the treatment of idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura is an autoimmune disorder, most common in young women. We treated 22 patients with this disorder (12 of whom were women) with danazol, an androgen with reduced virilizing capability, for two months or longer. Fifteen had undergone splenectomy, all were receiving glucocorticoids, and 18 had also been given other treatments.

Treatment of autoimmune hemolytic anemia with Vinca-loaded platelets.

We worked with a new strategy for the treatment of autoimmune hemolytic anemia (AIHA) of the warm antibody type. Platelets were loaded with Vinca alkaloids and reacted with antiplatelet antibodies to facilitate their phagocytosis by macrophages, resulting in a measure of selective delivery of the drugs to the cells of the mononuclear phagocyte system, which destroy RBCs in AIHA. Four patients were studied.

Stability and melting kinetics of structural domains in the myosin rod.

The thermal stability and melting kinetics of the alpha-helical conformation within several regions of the rabbit myosin rod have been investigated. Cyanogen bromide cleavage of long myosin subfragment-2 produced one coiled-coil alpha-helical fragment corresponding to short subfragment-2 with molecular weight 90,000 (Mr = 45,000) and two fragments from the hinge region with molecular weights of 32,000 to 34,000 (Mr = 16,000 to 17,000) and 24,000 to 26,000 (Mr = 12,000 to 13,000). Optical rotation melting experiments and temperature-jump kinetic studies of long subfragment-2 and its cyanogen bromide fragments show that the hinge and the short subfragment-2 domains melt as quasi-independent co-operative units.

Cross-bridge movement in muscle and the conformation of the myosin hinge.

The force-generating mechanism in muscle is discussed and it is shown that a helix-coil transition in the S-2 link of the cycling cross-bridge is compatible with the physical and chemical properties of this region of the myosin molecule. Thermal melting and temperature-jump experiments are described demonstrating that the light meromyosin-heavy meromyosin (LMM-HMM) hinge domain of S-2 is a segment of low thermal stability. This region can undergo alpha-helix-random coil transitions on a time-scale comparable to the quick-recovery tension transient observed when isometrically contracting muscle is abruptly shortened or stretched.

Sugar transport by the bacterial phosphotransferase system. Studies on the molecular weight and association of enzyme I.

Studies were conducted on the physical properties of Enzyme I, the first protein in the Salmonella typhimurium phosphoenolpyruvate:glycose phosphotransferase system. Since values lower than those previously reported for the monomer molecular weight were obtained, experiments were performed to determine whether Enzyme I had been partially degraded during isolation of homogeneous protein. Crude extracts and partially purified and homogeneous protein preparations exhibited identical behavior in crossed immunoelectrophoresis analyses, indicating that the isolated protein represented native, intact Enzyme I.

Conformational transition in the myosin hinge upon activation of muscle.

We have determined the rates of chymotryptic proteolysis of the myosin hinge region in glycerinated rabbit psoas fibers and myofibrils in in rigor-inducing, activating, and relaxing buffers. The time course of formation of light meromyosin (LMM) provides a specific probe for cleavage within the hinge domain. In rigor-inducing and relaxing buffers proteolysis within the hinge is depressed, but on activation LMM is formed at a markedly increased rate, which is dependent on the concentration of MgATP.

Functional evidence for renorenal reflexes in the rat.

Acute left renal denervation in anesthetized volume-expanded rats produced an ipsilateral diuresis and natriuresis in 19 animals. A simultaneous decrease of glomerular filtration rate, p-aminohippurate clearance, urinary volume (P < 0.002), and percentage of filtered sodium excreted (4.

A selective inhibitor of cell proliferation from normal serum.

A factor in normal serum that selectively and reversibly inhibits proliferation of cells in culture has been enriched 160-fold from calf serum by sequential ammonium sulfate precipitation, gel filtration, and lectin-affinity chromatography. DNA synthesis of normal (but not transformed) rat hepatocytes, human lymphoblast lines, and mitogen-stimulated murine spleen cells is inhibited by greater than 90%, and Vero, murine myeloma, MELC, and a human colon carcinoma cell line to a lesser extent. Growth of other cell lines tested was not affected.

The Ph.D. to M.D. program: the seven-year mark.

The Ph.D. to M.

On the origin of the contractile force in skeletal muscle.

Analysis of the early tension responses after abrupt step changes in the length of isometrically contracting skeletal muscle shows that the magnitude of the recovery tension (T2) and the time dependence of this process at various step displacements give a good correlation with the behavior expected for a helix-coil transition in the subfragment-2 (S-2) region of myosin. The "instantaneous" tension response (to T1) after the step change in length appears to have its origin in compliance within the coil region of S-2, which is formed through helix melting at the moment of force generation.

Renal metabolism of N6,O2'-dibutyryl adenosine 3',5'-monophosphate.

Metabolism of dibutyryl cyclic AMP was studied by including the 3H- or C-labeled nucleotide (0.1 mM, 5 mumol) in the recirculating perfusate of the isolated rat kidney. Kidneys were perfused with nucleotide for 60 min.

Reinforced matrices for pin-amalgam restorations reduce microleakage.

The considerable decrease in microkeakage in the compound-reinforced restorations may be due to the tighter fit of the matrix band at the gingival wall of the preparation, which allows better condensation and marginal sealing of the restoration. The compound prevents lateral migration of the band during condensation pressures.

Rapid helix--coil transitions in the S-2 region of myosin.

Temperature-jump studies on the long S-2 fragment (100,000 daltons) isolated from myosin show that this structure can undergo alpha-helix--random coil transitions in a time range approximating the cycle time of a crossbridge. Two relaxation times are observed after temperature jumps of 5 degrees C over the range 35--55 degrees C, one in the submillisecond (tau f) and the other in the millisecond (tau s) time ranges. Both processes exhibit maxima near the midpoint of the helix--coil transition (tm = 45 +/- 2 degrees C) as determined by optical rotation melt experiments.

Iatrogenic disorders from cancer treatment.

All cancer therapies have potential and often serious side effects. With judicious selection of therapies, the risks are acceptable as are the contributions to better care, including that of iatrogenic disorders from therapy. It should, again, be stressed that new drugs and new modalities in combinations of treatments increase iatrogenic disorders from cancer therapy; as this increase is more and more appreciated, adjustments in schedules are resulting in decreased incidences of such disorders.

Hazardous solid waste from domestic wastewater treatment plants.

The treatment of liquid wastes in municipal sewage treatment plants creates significant quantities of solid residue for disposal. The potential hazard from these wastes requires that their characteristics be determined accurately to develop environmentally sound management criteria. It is readily recognized that the sludge characteristics vary with the type and degree of industrial activity within a wastewater collection system and that these characteristics play a significant role in determining whether the material has potential for beneficial reuse or if it must be directed to final disposal.