Interleukin-5 is at 5q31 and is deleted in the 5q- syndrome

Human interleukin-5 (IL-5) is a selective eosinophilopoietic and eosinophil-activating growth hormone. By in situ hybridization this gene is mapped to chromosome 5q23.3 to 5q32. It is shown to be deleted in two patients with the 5q-syndrome and in one patient previously diagnosed with myelodysplasia whose condition had progressed to acute myeloblastic leukemia. The clustering of other genes involved in hematopoiesis (IL-3, granulocyte-macrophage colony-stimulating factor, feline sarcoma viral oncogene homolog, colony-stimulating factor 1) to the same region as IL-5 suggests a nonrandom localization and raises interesting questions concerning the evolution and regulation of these genes.     

Failure to prolong pancreatic islet allograft survival in rats with donor-specific blood transfusions and immunosuppression

The effects on pancreatic islet allograft survival of donor-specific blood transfusions (DST) in combination with pre- and posttransplant immunosuppression were studied. A total of 12 groups of rats (n=105) with chemically induced diabetes underwent islet allotransplantation. Multiple DST or third-party blood transfusions (TPT) were given prior to transplantation. Pretransplant immunosuppression consisted of azathioprine and prednisolone, and low-dose cyclosporin A was used for posttransplant immunosuppression. TPT, as well as separate or combined pre- and posttransplant immunosuppression without blood transfusions, did not prolong islet allograft survival. DST resulted in either primary nonfunction of the islet allografts or a markedly decreased islet allograft survival. These findings contrast with the beneficial effect of DST on whole-organ allograft survival in rats previously described by others.     

Bactericidal effects of ticarcillin-clavulanic acid against Legionella pneumophila pneumonia in immunocompromised weanling rats.

A model of acute Legionella pneumophila pneumonia in neutropenic weanling rats was developed as a means of assessing the efficacies in vivo of the beta-lactams ticarcillin, ticarcillin-clavulanic acid, and clavulanic acid, agents active against the organism in vitro. Weanling rats were dosed with cyclophosphamide 3 days before and immediately prior to infection by intrabronchial intubation with L. pneumophila. The bacteria persisted in the lungs of untreated animals at high counts (5.0 to 7.0 log10 CFU/g of lung tissue) for up to 168 h after infection, and the histological characteristics of the infection were similar to those of the disease in humans. Transmission electron micrography revealed the presence of L. pneumophila multiplying within alveolar macrophages. Therapy with ticarcillin was ineffective in reducing the bacterial numbers in the lung tissue, whereas ticarcillin-clavulanic acid and clavulanic acid were active, producing bactericidal effects similar to those of erythromycin. The ticarcillin-clavulanic acid combination was significantly more efficacious (P less than 0.01) than corresponding doses of clavulanic acid alone. Synergistic activity between ticarcillin and clavulanic acid against L. pneumophila has been demonstrated in vivo, and the combination showed activity similar to that of erythromycin.     

Measurement of the clinical status of patients with breast cancer: evidence for the validity of self assessment with linear analogue scales

We have assessed the validity of a method of measurement for describing the clinical status of patients with breast cancer. One hundred and nine patients with breast cancer assigned numerical values to their own state of health using linear analogue scales. We have shown previously that this method of measurement is reliable and corresponds well with other methods of assessment. Validity was assessed in this study by examining the ability of measurements to distinguish between groups of patients who differed either in the presence of metastatic disease or in the treatments they were receiving. All patients completed the same set of 29 linear analogue scales that enquired about the severity of health related problems and symptoms. In general, patients with metastatic disease were clearly distinguished from patients without metastases by their scores on items related to physical function. Patients receiving chemotherapy were distinguished from those not receiving chemotherapy by their scores on treatment related toxicities. Measures of psychological and social health were similar in patients receiving chemotherapy regardless of disease status. These results provide further support for the validity of measurement of clinical status with linear analogue scales scored by patients.     

Purification from a human lung cancer cell line of a water soluble molecule mediating leukocyte adherence inhibition for patients with lung cancer

Soluble lung tumor activity as determined by LAI2 was enriched by physicochemical methods from chemically - defined spent medium of a lung cancer cell line (NCI-H69). To identify the polypeptide carrying the antigenic determinant, splenic lymphocytes of BALB/c mice were immunized with the enriched isolate and hybridized with mouse plasmacytoma cells. Eight hybrids were cloned successfully and produced MAbs that immunoprecipitated principally a single chain of Mr 40,000 (p40) as well as minor chains of Mr 25,000 (p25) and Mr 13,000 (p13) which were probably degradation products of p40. On 2D gels, p40 was composed of 7 spots with a p1 of 6.3 to 7.6, which was not altered by neuraminidase digestion. Affinity chromatography with MAb anti-p40 absorbed p40 and LAI activity. The bound and recovered fraction was enriched for p40 and LAI activity. Affinity-purified p40 also contained the previously identified p25 and p13 as well as a Mr 32,000 peptide (p32). MAb anti-p40 was directed to a common framework determinant on p40 since MAb anti-p40 bound to cancer cells from other organs. The comparatively lung cancer organ-specific determinant recognized by leukocytes from lung cancer patients was not recognized by the MAb. Affinity-purified p40 triggered LAI for leukocytes from patients with lung cancer but not for leukocytes from control subjects or patients with colon cancer or malignant melanoma in rigorous blind testing. Crossreactivity was observed with leukocytes from patients with breast cancer. LAI activity of affinity-purified p40 seems unlikely to result from an unidentified impurity. Thus a p40 molecule has been purified that is expressed on the membranes of lung cancer cells and triggers immunologically-mediated LAI.     

Studies on Australian snake venoms. Part 1: The haemodynamic effects of brown snake (Pseudonaja) species in the dog

The haemodynamic effects of Brown Snake (Pseudonaja) species (textilis, nuchalis, affinis) were investigated in anaesthetised, mechanically ventilated dogs. Blood pressure decreased to minimal levels five minutes after intravenous envenomation. Hypotension was accompanied by significant decrements in cardiac output and stroke volume and a rise in peripheral vascular resistance. Heart rate increased transiently during 0.5-2.0 minutes after envenomation but had declined below resting levels five minutes after envenomation. No statistically significant change was recorded in central venous pressure. Depression of myocardial contractility is postulated as the mechanism of venom induced hypotension.     

Isolated perfusion of extremities for metastatic melanoma from an unknown primary lesion

Since 1957, 822 patients with invasive malignant melanoma of the limbs were treated by regional perfusion at the Tulane Medical Center. Between 1958 and 1982, there were 32 patients with regional metastatic melanoma from an unknown primary site involving either the upper limb and axillary lymph nodes or lower limb and femoral or inguinal lymph nodes. This group represents 3.5% of patients with regional melanomas treated during this period. There were 16 patients with upper limb regional metastases and 14 patients with lower limb metastases. Sixteen patients had stage IIIB disease (ie, regional lymph node metastases), ten had stage IIIA disease (ie, satellitosis), and four had stage IIIAB disease. Six patients had a history of a suggestive limb lesion that had completely regressed and showed no residual tumor on biopsy. All 30 patients were treated by regional isolated perfusion and regional lymph node dissection, with surgical excision of in-transit disease when possible. The cumulative five-year survival for all patients is 50%. Interestingly, the patients with a history of a lesion that regressed had 85% cumulative five-year survival, and the patients with stage IIIB disease did almost as well, with 62% surviving for five years.     

Efficacy of topical mupirocin against an experimental Staphylococcus aureus surgical wound infection

The efficacy of topically-applied mupirocin was evaluated against an experimental surgical staphylococcal wound infection in the guinea-pig. A suture impregnated with Staphylococcus aureus was inserted into a superficial wound, and topical therapy with mupirocin ointment was started 24 h after infection. In non-treated wounds, the bacterial counts increased to greater than 10(6) organisms/wound in the majority of animals at 24 h, remaining at this level for up to seven days. Therapy with placebo ointment (polyethylene glycol base) was ineffective, whereas twice daily application of mupirocin ointment resulted in elimination of the staphylococci. Mupirocin was as effective as topically-applied fusidic acid cream in reducing the bacterial counts of infected wounds.     

Experimental cerebral ischemia studied using nuclear magnetic resonance imaging and spectroscopy

The effects of short-duration forebrain ischemia on cerebral metabolism in the rat have been studied using several nuclear magnetic resonance (NMR) techniques. In vivo phosphorus-31 (31P) NMR spectroscopy showed that the model produces rapid cerebral energy failure and acidosis. Reperfusion was accompanied by recovery of high-energy metabolites in about 30 minutes, with a slower recovery of pH. Proton (1H) NMR spectra of perchloric acid extracts of selected brain regions showed that levels of alanine and gamma-aminobutyric acid (GABA) were elevated and the level of glutamate was depressed immediately after the ischemic insult, returning to normal by 24 hours. The lactate level remained elevated for up to 7 days after ischemia, suggesting ongoing abnormal mitochondrial function. Postischemic cerebral glucose metabolism was monitored using carbon-13 (13C)-labelled glucose as an NMR probe. Glycolysis was impaired immediately after the ischemic insult, resulting in accumulation of glucose in the tissue and reduced formation of amino acids and tricarboxylic acid cycle intermediates. Glycolysis recovered by 1 hour, but underwent a secondary decrease at 24 hours, the time at which neuronal injury became manifest histologically and physiologically. Nuclear magnetic resonance imaging was used to follow the regional development of tissue injury in selectively vulnerable brain regions. Striatal changes were evident by 24 hours after reperfusion, increasing in intensity and accompanied by hippocampal changes by 48 hours, then becoming less pronounced by 72 hours. Histologic analysis of regional neuronal injury correlated well with the imaging results, establishing NMR imaging as a noninvasive method of visualizing the regional development of ischemic tissue injury.