Legionella and the enterobacterial common antigen.

Legionella pneumophilia Philadelphia 1 and Knoxville 1 were examined by in vitro hemagglutination and dermal hypersensitivity reactions in guinea pigs for the presence of the enterobacterial common antigen. No ECA was found and no cross reactivity was demonstrated between ECA and the proteinaceous cross reacting antigen.

Experience with hypercalcemia and osteoporosis of neoplastic disease.

Hypercalcemia and hypercalcemic crisis are common and often life threatening complications of neoplastic disease. Even moderately increased mobilization of skeletal calcium can result in significant osteoporosis. This in turn can give rise to pathologic fractures, often followed by pulmonary fat embolism and death.

Studies on the pathophysiology and therapy of osteoporosis.

Etiologic and pathologic factors in clinical osteoporosis are reviewed. Techniques were developed to determine total skeletal calcium content with in vivo neutron activation analysis and to induce osteoporosis (in about three months) with low calcium diet, corticosteroid or heparin treatment in experimental animals. Genetic influence was demonstrated: C3H/St (Ha) mice were more susceptible to osteoporosis by all three modalities than C57B1/6 (J) mice.

Antineoplastic effect of the xanthine derivative Trental.

The xanthine derivative, Trental (pentoxifylline) was found to inhibit several human leukemic and lymphoma cell lines in tissue cultures. Optimal concentrations were less inhibitory for a normal B-lymphocyte cell line then for the neoplastic cell lines. In fact, small concentrations stimulated DNA synthesis in the normal cell line.

Effect of second tumors and of prostaglandin-leukotriene inhibitors on radiation therapy of transplanted rodent tumors.

The prostaglandin and leukotriene inhibitor sodium meclofenamate (SM) failed to influence radiation therapy induced regression of 6C3HED Gardner lymphosarcoma in C3H mice. Recurrence after radiation therapy, however, was reduced by treatment with SM. During these experiments, we observed that if a tumor was "cured" by radiation therapy, it required inoculation of a larger number of cells to establish a second tumor.

Studies on the management and prevention of vasoocclusive crisis in sickle cell disease.

In vitro deformability of red blood cells from SS-genotype patients in vasoocclusive crisis of sickle cell disease was significantly improved by the in vitro addition of the xanthine derivative pentoxifylline (Trental). Monkeys transfused with discarded sickle cell crisis blood showed aggregation of red cells and platelets on metal screens inserted into arterio-venous anastomoses. This phenomenon could be prevented by pretreatment of the animals with 24 mg/kg of pentoxifylline.

Study of antiosteoporotic agents in tissue culture.

Cultures of osteoblast-like cells were established from calvariae of Sprague-Dawley rats. Pentoxifylline increased cAMP levels and calcium uptake in these cultures. However, calcium uptake increased at lower levels than required to increase cAMP levels.

Activation and immunoregulation of human B lymphocytes.

Immunocompetent cells communicate via direct cellular contact and/or by the release and binding of soluble mediators. These soluble mediators transmit signals for growth and differentiation of various cell types. We have been intensively studying the regulation of human B lymphocytes and have focused on the events which occur following stimulation of mature, resting B cells with antigen or an antigen equivalent, anti-immunoglobulin antibody.

Studies on osteoporosis X. Effect of estrogen-progestin combination on heparin-induced osteoporosis.

Neutron activation analysis was employed to determine total body calcium in C3H/St(Ha) female mice. As 99% of body calcium is in bone, loss of calcium was used as an index of bone loss (osteoporosis). Heparin (500 U/kg b.

The role of the tissue adhesive fibrin seal (FS) in esophageal anastomoses.

Following surgical removal of esophageal tumors, leakage and mediastinitis is a frequent and often fatal complication. A new method has been developed to seal suture lines in the esophagus with preparations containing fibrinogen, cold insoluble globulin, factor XIII, antiplasmin, platelet growth factor, thrombin, and calcium chloride. In experimental animals operated on by standard methods, esophageal leakage developed in 50% of the animals and death in 40%.

Prognostic parameters in recurrent malignant melanoma.

In 361 patients with recurrent malignant melanoma, the clinical stage was the strongest determinant of subsequent survival (P less than 0.01). In Stage IV, the number of initial, distinct lesions was important.

The role of pentoxifylline in the prevention of tumor cell implantation.

Short-term administration of pentoxifylline concurrent with intraportal or intravenous instillation of W163 adenocarcinoma was ineffective in preventing tumor cell implantation in adult male rats.

The role of fibrin adhesive in vascular surgery.

Fibrin Seal (FS) (a natural adhesive material composed of fibrinogen, cold insoluble globulin, factor XIII, platelet growth factor, antiplasmin thrombin, and calcium chloride) was utilized in the construction of vascular anastomosis of the femoral artery of mongrel dogs. A significant decrease in the number of sutures necessary to achieve adequate anastomosis and minimize the likelihood of postoperative bleeding was noted. There was no long-term increase in tissue reaction or decrease in arterial patency.

Protection of normal tissues with 2-aminoethylisothiouronium during local pelvic radiation in monkeys.

Intestinal and bladder injury are the main limiting factors to radiation therapy in patients with pelvic neoplasms. 2-Amino-ethylisothiouronium (AET) is a radiation-protective agent when given systemically but absorbs poorly from the intestines. Accordingly, it was explored for the local protection of the bowel and bladder during radiation to the pelvis.

In vivo safety of hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase in a large animal model for phenylketonuria.

Hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase (PAL) were developed for the in vivo depletion of phenylalanine (Phe) in circulating blood. A series of experiments was conducted with a large animal model in order to explore its safety for clinical use. The level of red blood cells, white blood cells and platelets did not change during a 2-hr application of the reactors in anesthetized, heparinized dogs and monkeys with experimental hyperphenylalaninemia.

Antitumor studies of 2-amino-2-thiazoline and other tumor-modifying agents.

2--amino-2-thiazoline (AT) and 1-thiazolidine-4-carboxylate (TC, thioproline), which have been previously proposed as agents of reverse transformation, have been examined as antitumor agents in several rodent tumor systems. AT administration reduced tumor incidence in sym-dimethylhydrazine treated outbred ICR Swiss female mice and doubled the survival of DBA/2Ha female mice infected with polycythemic Friend leukemia virus. Indomethacin, pentoxyphylline, RA233 and diethyldithiocarbamate (DTC), with potential for altering host or tumor prostaglandin levels, platelet aggregation and host immunity, respectively, ranged from marginally effective to ineffective against Friend virus infection.

Clinical experience with prostaglandin E1 in the treatment of arteriosclerosis obliterans. A preliminary report.

Eleven patients with severe arteriosclerotic disease of the lower extremities who were unsuitable for surgical bypass procedures or who had surgical bypass failure have been treated with prostaglandin E1. The patients all responded well to the prostaglandin treatment, except for one patient who required an above the knee amputation. Subjective evidence of pain and swelling disappeared and the patients' narcotic requirements were reduced.

Studies on osteoporoses. XI. Effects of a methylxanthine derivative. A preliminary report.

Heparin (500 U/kg s.c. B.

Studies on osteoporosis. IX. Effect of fluoride on steroid induced osteoporosis.

Neutron activation analysis was employed to determine total body calcium in 5-8 month and 15-18 month old C3H/St(Ha) and C57/BL6 (JACOBS) female mice. Ninety-nine percent of calcium is in bone and loss of calcium was used as an index of osteoporosis. Prednisolone (50 mg/kg q.

Studies on osteoporosis VII. Effect of 17 beta-hydroxy-4-estren-3-one 17-decanoate on experimental osteoporosis.

Total body neutron activation analysis was employed to measure total calcium in C3H/St (Ha) female mice. Ninety-nine percent of total body calcium is in bone and loss of calcium was used as an index of osteoporosis. Heparin (500 U/kg B.

Depletion of phenylalanine in the blood of phenylketonuric patients using a PAL-enzyme reactor. An in vitro study.

Blood samples obtained from eight adult phenylketonuric individuals had a mean phenylalanine level of 25 mg/dl. When these samples were circulated through multitubular enzyme-reactors prepared with immobilized phenylalanine ammonia lyase an average of 77% of phenylalanine was metabolized within 30 minutes. We conclude that phenylalanine in human phenylketonuric blood is just as susceptible to metabolism by PAL-enzyme reactors as phenylalanine that is added to normal blood, or that is circulating in dogs and monkeys made hyperphenylalaninemic by experimental means.

Renal prostaglandin E2 biosynthesis: dependence on angiotensin II.

To study the interaction of the prohypertensive renin-angiotensin axis with the antihypertensive renal prostaglandins, angiotensin-converting enzyme inhibition (captopril and teprotide) and angiotensin blockade (Sar1-Ile8-AII) were produced in rabbits in vivo and renal slice prostaglandin E2 was measured in vitro after 30 minutes of incubation in Krebs-Ringer HCO3- buffer. In rabbits with angiotensin-converting enzyme inhibition, de novo prostaglandin E2 synthesis decreased in cortical, outer medullary and papillary slices by 85, 52 and 47 percent, respectively. Similar degrees of inhibition were observed with angiotensin blockade.

Hemostasis in experimental pulmonary injury.

Fibrin Seal (consisting of fibrinogen, cold insoluble globulin, factor XIII, antiplasmin, platelet growth factor, thrombin, and calcium chloride), cryoprecipitate, at Avitene were applied to areas of pulmonary wedge resections in dogs and cynomologus monkeys in an attempt to stop bleeding and air leakage. In the control groups, hemorrhage persisted. Comparing the three hemostatic agents used.

Studies on osteoporosis VI. Effect of human and salmon calcitonin on experimental osteoporosis.

Neutron activation analysis was employed to determine total body calcium in C3H/St (Ha) female mice. Ninty-nine percent of total body calcium is in bone and loss of calcium was used as an index of osteoporosis. Heparin (500 U/kg B.

Attempts to bypass the need for splenectomy in splenic injury.

Within the last decade spleen salvage has been a controversial issue. Only recently, with the advances and utilization of modern technology in surgery, spurred by a better understanding of this immunologically important organ, preservation has become a reality. Numerous approaches have been suggested.