Immunological effects of cancer chemotherapy in malignant melanoma

Summary The effects on the immune system of highdose cyclical combination chemotherapy were studied in nine patients with advanced malignant melanoma. Chemotherapy consisted of monthly cycles of dimethyl triazeno imidazole carboxamide 150 mg/m² i.v. daily from days 1–5, cyclophosphamide 1000 mg/m² i.v. on day 5, and vincristine 1.4 mg/m² i.v. on day 5.Immunological testing was carried out prior to treatment and at weekly intervals during the first month.B, T and non-B, non-T cell numbers all tended to fall early in the cycle as did the phytohaemagglutinin(PHA)-induced transformation and PHA-induced cytotoxicity to chicken red cells. Although PHA-induced transformation and cytotoxicity usually returned to normal by day 29, B and T cell numbers often remained subnormal. In contrast, levels for antibody-dependent, cell-mediated cytotoxicity (ADCC) were relatively stable throughout the cycle. Two patients with subsequent tumour response to therapy had rebound supranormal PHA transformations between weeks 1 and 3 of the first cycle. No other changes correlated with prognosis in individual patients.Analysis of the temporal relationships between PHA transformation, PHA-induced cytotoxicity, and ADCC supported the concept that the three assays reflect the function of separate mononuclear cell subpopulations.The stability of ADCC is of particular interest in view of other work suggesting that this function may be important in immune responses to tumours, including melanoma.Work was supported by grants from the National Health and Medical Research Council and the Western Australian Arthritis and Rheumatism Foundation, and the Cancer Council of Western Australia     

The peptidoglycan crosslinking enzyme system in Streptomyces strains R61, K15 and rimosus

The DD-carboxypeptidase-transpeptidase enzyme system in Streptomyces strain K15 consists of: (1) a membrane-bound transpeptidase capable of performing low DD-carboxypeptidase activity; and (2) a set of DD-carboxypeptidases: (a) membrane-bound, (b) lysozyme-releasable and (c) exocellular, having low transpeptidase activities in aqueous media and at low acceptor concentrations. The DD-carboxypeptidases are related to each other and may belong to the same pathway leading to enzyme excretion. A similar enzyme system occurs in Streptomyces strain R61 except that the membrane-bound DD-carboxypeptidase activity is low when compared with the membrane-bound transpeptidase activity. In Streptomyces rimosus the enzyme system consists almost exclusively of the membrane-bound transpeptidase and the levels of membrane-bound, lysozyme-releasable and exocellular DD-carboxypeptidases are very low.     

Bahavioral fever in crayfish

Crayfish (Cambarus bartoni) were tested individually in an electronic shuttlebox thermoregulatory device which allowed them to control water temperature, and thereby their body temperature, by their movements.Crayfish which initially selected 22.1°C water increased their preferred temperature by 1.8°C following injection of killed bacteria (Aeromonas hydrophila) into the gill cavity.This behavioral fever appears similar to that of vertebrates, and may enhance host defense reactions against pathogens.     

Ultra-short acting beta-blockers: a proposal for the treatment of the critically ill patient

Beta-blockade is of proven value in the therapy of acute myocardial infarction but, unfortunately, may produce cardiac failure by removal of needed sympathetic support. The long duration of action of available blockers (hours) makes reversal of failure a complicated problem and precludes rapid modification of therapy to match changing autonomic conditions. To improve the safety and efficacy of beta-blockade in this setting we have developed the concept of ultra-short beta-blockade and have identified a novel beta-blocker (ASL-8052) which possesses a duration of action less than 15 minutes. This compound is cardioselective and possesses efficacy in an animal model of acute myocardial infarction. It, therefore, appears to be suitable for rapid attainment of controlled levels of beta-blockade via intravenous infusion and rapid recovery from beta-blockade if required by the clinical situation. The compound should, therefore, be useful for safe therapy in critically ill cardiac patients.     

Isopropanol enhancement of carbon tetrachloride metabolism in vivo

We examined the effects of isopropanol (ISOP) pretreatment on the metabolism of ¹⁴CCl₄ to ¹⁴CO₂ and CHCl₃ exhaled in the breath, to ¹⁴C metabolite excreted in 24 hr urine and feces from 0 to 24 hr, and to ¹⁴C metabolite bound to liver at 24 hr. Fasted male rats were given 0.1 or 2.0 mmoles ¹⁴CCl₄/kg. ISOP pretreatment, which markedly enhanced the hepatotoxicity of CCl₄, selectively enhanced the rate and total extent of ¹⁴CO₂ and CHCl₃ metabolite exhalation. The pathways of CCl₄ metabolism leading to CO₂ and CHCl₃ metabolite formation may be more relevant to the hepatotoxicity of CCl₄ than the pathways leading to urinarym fecal or covalently bound metabolites.     

The accessory olfactory system and its role in the pheromonally mediated suppression of oestrus in grouped mice

Mice were grouped to induce suppression of oestrus and subjected to removal of the vomeronasal organs or treatment with CB 154 which lowers prolactin levels. Both treatments overcame the suppression of oestrus after 72 h. Oestrus suppression was induced in lesioned mice by haloperidol treatment which raises plasma prolactin, and oestrus returned some 72 h after withdrawal of haloperidol treatment.     

Active transport of alpha-aminoisobutyric acid in freshly prepared rat hepatocytes

The transport of alpha-aminoisobutyric acid in freshly prepared rat liver cells was saturable and exhibited a K_t of 13.9 × 10^?3M and a_max of 28.6 umoles/ml intracellular fluid/30 min. The system required the presence of sodium and was sensitive to ouabain. Anaerobiosis, 2,4-dinitrophenol and low temperature suppressed the uptake of the amino acid. Efflux studies also indicated that the majority of the intracellular amino acid was rapidly exchangeable and therefore probably present in the cell water in a free state. It is suggested that alpha-aminoisobutyric acid is transported into isolated rat hepatocytes by an active carrier system.     

Membrane potentials and resistances of giant mitochondria. Metabolic dependence and the effects of valinomycin

The membrane potentials and resistances of giant mitochondria from mice fed cuprizone have been studied. They were found to correspond approx. 10-20 mV, positive inside, and 2 M omega, respectively. These properties were found to be independent of the metabolic state. The microelectrodes were in the inner mitochondrial space since (a) the potentials in the presence of valinomycin depended on the K+ concentration of the medium and magnitude of the K+ diffusion potentials was consistent with the presence of a high internal concentration of K+, (b) almost identical results were obtained with mitochondria from which the external membrane had been removed and the cristae were evaginated, and (c) punch-through experiments, in which the microelectrodes were advanced until they emerged through the other side of the mitochondria, showed an identical membrane potential both in the presence and in the absence of valinomycin. The potentials were stable under a variety of conditions and showed no sign of decay of membrane leakiness. Detailed evidence that the impaled mitochondria are metabolically viable will be presented in a separate publication.