Assessment of heterospecific zona-free ovum penetration under fully defined conditions.

The prognostic value of the sperm penetration assay (SPA) using zona-free hamster ova has not been universally accepted. This is partly due to technical problems with the assay, resulting in 5-17% false negative results. The advantage of replacing albumin with defined synthetic polymers in the SPA culture media, increasing the calcium gradient and incorporating potential active tract agents and antioxidants, has been investigated.

Formation and stability of vincristine-tubulin complex in kidney cytosols. Role of GTP and GTP hydrolysis.

Vincristine-tubulin complex formed in the 100,000 g fraction of mouse kidney dissociated rapidly at 37 degrees in the absence of guanosine-5'-triphosphate (GTP). In the presence of 2 mM GTP, there was a substantial (2.8-fold) increase in complex stability; NaF (100 mM) but not beta-glycerophosphate (1 mM) also reduced the rate of dissociation.

Phase II testing of melphalan in children with newly diagnosed rhabdomyosarcoma: a model for anticancer drug development.

We describe events that led to successful testing of melphalan, one of the nitrogen mustard compounds, in children with newly diagnosed, poor-risk rhabdomyosarcoma (RMS). Preclinical studies with xenografts of human RMS, growing in the flanks of immune-deprived mice, had indicated superior oncolytic activity by melphalan compared with other agents commonly used to treat this tumor. However, in a conventional phase II trial, melphalan failed to produce partial responses in 12 of 13 heavily pretreated patients with recurrent tumors.

Evaluation of 3-(p-fluorophenyl)-L-alanyl-3-[m-bis-(2-chloroethyl) aminophenyl]-L-alanyl-L-methionine ethyl ester HCl (PTT.119) against xenografts of human rhabdomyosarcoma.

PTT.119 [p-F-phe-m-bis(2-chloroethyl)amino-L-phe-met ethoxy HCl], a synthetic tripeptide mustard, was evaluated for therapeutic efficacy against a spectrum of childhood rhabdomyosarcomas (RMS) maintained as xenografts in immune-deprived mice. These xenografts were established from previously untreated tumors, and sublines were selected in mice for resistance to L-phenylalanine mustard (L-PAM).

Acoustic reflex amplitude and noise-induced hearing loss.

Acoustic reflex maximum amplitude measurements elicited both contralaterally and ipsilaterally were obtained from subjects with noise-induced hearing loss and compared with those obtained from normal-hearing subjects. The eliciting signal was a pure tone of 1 kHz presented for 1,000 ms. The groups were matched on age, sex, static immittance and ear canal volume.

Characteristics of thymidylate synthase purified from a human colon adenocarcinoma.

Thymidylate synthase has been purified greater than 4000-fold from a human colon adenocarcinoma maintained as a xenograft in immune-deprived mice. In this disease, the enzyme is an important target for the cytotoxic action of 5-fluorouracil, which is influenced by the reduced folate substrate CH2-H4PteGlu. Due to the importance of this interaction, and the existence in cells of folate species as polyglutamyl forms, the interaction of folylpolyglutamates with thymidylate synthase was examined.

Disappearance of high-grade left anterior descending stenosis after revascularization.

Complete resolution of a high-grade left anterior descending (LAD) stenosis 6 months after revascularization with a left internal mammary artery (IMA) graft and the first reported case of spontaneous IMA graft spasm during repeat cardiac catheterization for continued atypical chest pain in the same patient are reported. Mechanisms involving regression of atherosclerosis and atypical spasm are briefly discussed.

Reciprocal cross-resistance in human rhabdomyosarcomas selected in vivo for primary resistance to vincristine and L-phenylalanine mustard.

Primary resistance to vincristine (VCR) has been selected in rhabdomyosarcoma xenograft HxRh12 by sequential administration of VCR at 1.5 and subsequently 3 mg/kg/passage. The resistant tumor (HxRh12/VCR-3) was approximately 4-fold resistant to VCR and resistance was stable in the absence of selecting pressure (greater than 2 yr).

THE DEGRADATION OF CHLOROPHYLL - A BIOLOGICAL ENIGMA.

Some 10 tonnes of chlorophyll are destroyed each year on land and in the oceans. The fate of these chlorophylls is, however, largely unknown. This review describes the developmental stages at which chlorophyll breakdown occurs in aquatic and terrestrial biological systems, and the destruction arising from herbivory, disease, pollution and other physical hazards.

Therapeutic selectivity of vinca alkaloids: a role for guanosine 5'-triphosphate?

Tubulin, the protein subunit of microtubules, is considered a target for antimitotic agents such as colchicine, maytansine and the vinca alkaloids vincristine and vinblastine. Of these agents, only vincristine and vinblastine have been found to have clinical utility for treatment of human neoplastic disease. The basis for therapeutic selectivity was examined in a comprehensive model in which human rhabdomyosarcomas were grown as xenografts in mice.

Characterization of cell lines derived from xenografts of childhood rhabdomyosarcoma.

Three human rhabdomyosarcoma cell lines (Rh10, Rh18, and Rh28) have been established from three independently derived xenografts. These lines have been characterized as mesenchymal in origin (reactivity to desmin and vimentin antibodies) and as expressing a human fetal muscle surface antigen recognized by monoclonal antibody 5.1 H11.

The role of acyl-CoA: cholesterol acyltransferase in the metabolism of free cholesterol to cholesteryl esters or bile acids in primary cultures of rat hepatocytes.

Sandoz compound 58-035 has been shown to inhibit acyl-CoA: cholesterol acyltransferase activity in a variety of cell types. We have shown that it does not inhibit rat liver microsomal cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme of bile-acid synthesis, but it does inhibit acyl-CoA: cholesterol acyltransferase in both the microsomal fraction and in rat hepatocyte monolayers. To test the role of acyl-CoA: cholesterol acyltransferase in these cells, monolayers were incubated over 5 h in the presence and absence of 58-035 and in the presence of increasing amounts of mevalonic acid to provide a source of cholesterol.

Randomised trial of endoscopic versus percutaneous stent insertion in malignant obstructive jaundice.

Patients with biliary obstruction due to malignant disease, and judged unfit for open operation, were randomised to have a biliary stent inserted either endoscopically via the papilla of Vater or percutaneously. Analysis after 75 patients had been entered showed that the endoscopic method had a significantly higher success rate for relief of jaundice (81% versus 61%, p = 0.017) and a significantly lower 30-day mortality (15% versus 33%, p = 0.

Visualization of pig sperm chromosomes by in-vitro penetration of zona-free hamster ova.

Zona-free hamster eggs were penetrated by pig spermatozoa capacitated using bovine follicular fluid and Percoll gradients. A mean penetration rate of 80.1% was obtained from 5 ejaculates from 2 boars.

Scheduling of vincristine: drug accumulation and response of xenografts of childhood rhabdomyosarcoma determined by frequency of administration.

Vincristine (VCR) is an effective agent in the treatment of childhood rhabdomyosarcoma. Clinically, schedules differ in frequency of administration. To determine the influence of administration frequency, accumulation of VCR in xenografts of human rhabdomyosarcoma has been evaluated following administration of drug at 7- or 21-day intervals.

Haemophilus influenzae pericarditis successfully treated by catheter drainage.

Surgical drainage together with antibiotic therapy is generally considered the treatment of choice for purulent pericarditis. A case of culture-proven Haemophilus influenzae pericarditis is described in a young, previously healthy adult. Successful management of his illness included placement of an indwelling pericardial catheter and intravenous antibiotics.

Development and characterization of a human colon adenocarcinoma xenograft deficient in thymidine salvage.

In order to determine the contribution of thymidine (dThd) salvage to intrinsic resistance to antimetabolites (5-fluoropyrimidines, antifolates) in the human colon adenocarcinoma xenograft, H X GC3, a subline deficient in thymidine kinase has been developed. A cell line (GC3/M) was established in continuous culture that demonstrated a karyotype identical to that of the stem line of H X GC3 (46,X, - Y + 12). After inoculation of GC3/M cells into immune-deprived CBA/CaJ mice, the H X GC3/M xenografts retained histological, histochemical, and growth characteristics of the H X GC3 xenograft.

Determination of thymidylate synthase activity in colon tumor tissues after treatment with 5-fluorouracil.

The formation and isolation of [6-3H]FdUMP-thymidylate synthase-5,10-methylenetetrahydrofolate covalent complex have been examined in tumor cytosols incubated with albumin-dextran coated charcoal used to remove endogenous nucleotide. Charcoal suspension (10% charcoal, 0.5% albumin, 0.

Hypoxanthine:guanine phosphoribosyltransferase activity in primary human osteosarcomas. A rationale for therapy with methotrexate-thymidine rescue?

Hypoxanthine:guanine phosphoribosyltransferase (HPRT) activity was measured in 14 human osteosarcomas to test whether a subset of these tumors was deficient in the purine salvage pathway enzyme and thus provide a rationale for therapy with methotrexate-thymidine rescue. All tumors contained HPRT activity within the range previously reported for xenografts of human osteosarcoma. Three patients received methotrexate (3.

Development and characterization of human ependymoma xenograft HxBr5.

We describe the successful heterotransplantation of a human ependymoma in CBA/CaJ mice immune deprived by infant thymectomy and whole-body irradiation. The xenograft, HxBr5, was established from a fourth ventricular ependymoma, locally recurrent in an 11-yr-old girl who had been treated with radiation therapy to the posterior fossa. HxBr5 retains histological and ultrastructural fidelity to the tumor from which it was derived as does the DNA content, as confirmed by flow cytometric analysis.

A specific chromosomal abnormality in rhabdomyosarcoma.

A specific chromosomal abnormality, t(2;13)(q35;q14), was discovered in five cases of advanced rhabdomyosarcoma. It was identified directly in cells that had metastasized from bone marrow in one patient and in xenografts derived from the tumors of four other patients. The translocation was not restricted by histologic subtype, but was found in cases classified as alveolar, undifferentiated, or embryonal.