New clinical trials with interleukin-2: rationale for regional administration.

The recent availability of recombinant interleukin-2 (IL-2) has led to its rapid introduction as systemic agent against solid tumors. Much less has been undertaken so far in the exploration of the potential advantages of regional applications of IL-2. The potential advantages of regional administration of IL-2 include an ability to achieve higher levels of IL-2 at the site of the tumor, to abrogate local and systemic immunosuppression and to activate specific and nonspecific cytotoxic effectors, with avoidance or reduction of major organ toxicity of high-dose systemic IL-2 therapy.

Isolation and partial characterization of melanoma-associated antigens identified by autologous antibody.

The study of the autologous immune response to cancer avoids the difficulties encountered in the use of xenoantisera and may identify antigens of physiological relevance. However, the low titer and incidence of autologous antibody to melanoma have hampered further evaluation. By utilizing acid dissociation and ultrafiltration of serum, we have been able to augment the detectable autologous immune response to melanoma in the majority of patients studied.

Pharmacokinetics of oxytetracycline in clinical cases in the red-necked wallaby (Macropus rufogriseus).

Oxytetracycline, administered at 40 mg kg-1 by intravenous injection, was used as part of the treatment of three female red-necked wallabies, Macropus rufogriseus, with suspected Fusobacterium necrophorum infections. The plasma concentrations of this drug in blood samples collected at intervals up to 24 hours after administration were measured using a biological assay. The pattern of decline in plasma oxytetracycline concentration with time was consistent with a two-compartment model.

Independence of dysplastic nevi from total nevi in determining risk for nonfamilial melanoma.

In the determination of risk for melanoma, relatively little is known about the possible independence of two important predictors, total nevi and clinically dysplastic nevi. From a study conducted in Sydney, Australia [see J. J.

Intrapatient and interpatient comparison of tumor size and monoclonal antibody uptake in melanoma.

In two panels totaling 52 patients with melanoma who were imaged with In-111 labeled 96.5 or ZME-018 (ZME) monoclonal antibodies (MoAb), four patients demonstrated numerous metastases (greater than or equal to 20) in the subcutaneous tissues and peripheral lymph nodes. These constituted four intrapatient groups of tumors.

Dysplastic nevi in association with multiple primary melanoma.

Risk factors for multiple primary cutaneous melanoma were evaluated in a case-control study. Eight cases of multiple primary melanoma were matched on sex, age, and education to 24 first primary melanoma controls. Risk factors examined in the analysis included pigmentary characteristics, history of sun exposure, and nevi.

Hepatic iron overload in birds: analytical and morphological studies.

Hepatic iron content was determined in post mortem specimens from a wide range of avian species collected over a 12-month period. The majority (> 90%) of these specimens (n = 40) showed high iron content (up to 12 mg Fe/g tissue). The highest concentrations were associated with fibrosis and regenerative nodules.

Cell kinetics and longitudinal bone growth in birds.

The theory that links cell division in epiphyseal cartilage plates to overall growth of long bones has been extended from linear growth systems to those in which proliferating and hypertrophied cells are not arranged in columns. Consideration has also been given to the analysis of non-parallel growth systems. The theory is illustrated by examples from the growth of chicken bones.

A randomized phase I/II study of continuous versus intermittent intravenous interferon gamma in patients with metastatic melanoma.

Thirty patients with documented metastatic melanoma were randomly assigned to receive recombinant DNA-produced gamma-interferon (specific activity approximately, 20 MU/mg) intravenously (IV) over either two or 24 hours at dosages of 3, 30, 300, 1,000, or 3,000 micrograms/m2. Objective toxicity resembled that of alpha-interferon and included fever, chills, myalgias, headache, and fatigue. Neutropenia, elevations in liver enzymes, tachyarrhythmias, and CNS changes also were noted.

Comparison of gallium-67 versus indium-111 monoclonal antibody (96.5, ZME-018) in detection of human melanoma in athymic mice.

We compared the biodistribution of two radiolabeled, whole, tumor selective monoclonal antibodies [( 111In]96.5, [111In]ZME-018) to 67Ga in nude mice bearing a human melanoma known to express p97 antigen. Localization of gallium was determined 48 hr following i.

Scintigraphic detection of metastatic melanoma using indium 111/DTPA conjugated anti-gp240 antibody (ZME-018).

We evaluated the toxicity, pharmacokinetics, and localization of a monoclonal IgG2 alpha murine anti-human melanoma (gp240) antibody (ZME-018) that recognizes a tumor-associated cell surface glycoprotein of 240,000 molecular weight present in most melanomas. The antibody was conjugated with DTPA (diethylenetriamine pentaacetic acid) and labeled by chelation of 111In. One mg of antibody labeled with 5 mCi of 111In was infused, together with 0 to 40 mg of "cold" carrier ZME-018.

A Mössbauer spectroscopic study of the form of iron in iron overload.

There are major differences in the temperature dependence of the Mössbauer spectra of ferritin and haemosiderin extracted from the organs of humans suffering from transfusional iron overload. Iron overload can also occur in animal systems as a result of artificial treatments or dietary factors. None of the animal systems which were investigated in the present study showed evidence in their Mössbauer spectra for the presence of the haemosiderin found in transfusional iron overload in humans.

Perinatal mortality and season of birth in captive wild ungulates.

The magnitude of perinatal mortality in 50 species of captive wild ungulates born at the Zoological Society of London's collections at Regent's Park and Whipsnade between 1975 and 1985 is reviewed. Thirty-five per cent of 2471 ungulates born during this 11 year period died before six months old and most deaths occurred in the first week after birth. Similar findings have been reported at other zoos and in the wild.

Adrenal myelolipoma in the cottontop tamarin (Saguinus o. oedipus).

Two cases of myelolipoma in the cottontop tamarin (Saguinus o. oedipus) were found unequivocally within the adrenal gland, supporting an earlier suggestion that the adrenal gland was the possible origin of a juxtarenal myelolipoma in the same species. In the present study a 30-mm-diameter myelolipoma was present in the adrenal gland in case 1, whereas in case 2 the myelolipoma was only detected on histological examination.

Potential applications of the interferons in oncology: lessons drawn from studies of human melanoma.

The rationale for application of interferons in the treatment of melanoma is based on evidence suggesting that this tumor exhibits antigens capable of eliciting a host immune response. Agents that act as immunomodulators or that enhance the expression of tumor antigens may have greater therapeutic potential than agents that act solely as direct cytotoxic or antiproliferative agents. Data suggest that interferons may manifest all three categories of antineoplastic function.

Adenocarcinoma of the large bowel and colitis in captive cotton-top tamarins Saguinus o. oedipus.

The gross and microscopic appearance of large bowel adenocarcinoma in two young adult, captive-born cotton-top tamarins is described. A retrospective examination of sections of colons from other animals that had died in the colony revealed a high incidence of chronic colitis. The adenocarcinomas, which resembled those reported from colonies of this species in the U.

Human melanocytes cultured from nevi and melanomas.

The requirements for growth factors of human melanocytes in culture may be dependent on the stage of malignant transformation. Several factors synergistically promote the viability and proliferation of human neonatal melanocytes in culture. They are TPA (12-O-tetradecanoyl-phorbol-13-acetate), isobutylmethyl xanthine, cholera toxin, and as yet unidentified factors from extracts derived from several cell lines and human placenta.

Prognostic role of antibody reactivity to melanoma.

Antibody reactivity against cultured allogeneic melanoma Y-Mel 81:180 was studied in 43 patients who participated in an adjuvant trial for stage I and II melanoma. Serum samples were obtained at trial entry within 2 mo of definitive surgery. At the time of serum acquisition, all patients were free of disease by physical examination and routine radiologic and laboratory parameters.

Diagnosis of the dysplastic nevus in different populations.

Because of the relationship of the dysplastic nevus to melanoma, physicians are being encouraged to identify the clinical features of this newly defined entity. However, the dysplastic nevus was originally characterized in the familial setting, and application of equivalent criteria to the general population will be disappointing. The ability of the clinician to diagnose the presence of dysplastic nevi will be markedly influenced by the true underlying prevalence of dysplastic nevi in the population subjected to the examination.