Identification of LytSR-regulated genes from Staphylococcus aureus

In this report, the characterization of a Staphylococcus aureus operon containing two LytSR-regulated genes, lrgA and lrgB, is described. Sequence and mutagenesis studies of these genes suggest that lrgA encodes a murein hydrolase exporter similar to bacteriophage holin proteins while lrgB may encode a protein having murein hydrolase activity.     

Expression and regulation of c-kit receptor and response to stem cell factor in childhood malignant T-lymphoblastic cells

The cytokine stem cell factor (SCF) synergizes with IL-7 to enhance the proliferation of thymocytes. We therefore investigated the role of the SCF receptor, the protooncogene c-kit, in the pathogenesis of pediatric T-lineage malignancies. Expression and regulation of c-kit in cells from children with non-Hodgkin's lymphoma (T-NHL) or acute lymphoblastic leukemia (T-ALL) and the proliferative effect of SCF on these cells were examined in seven cell lines and 21 biopsy tumor cell preparations. Inducibility of c-kit receptors by SCF, IL-1beta, IL-2, IL-7, TGF-beta, TNF-alpha, PMA or calcium ionophore A23187 was studied by flow cytometry (FCM). C-kit receptors were detected in three out of seven T-lymphoblastic cell lines and in nine out of 21 biopsy tumor cell preparations. Upregulation of c-kit could be induced by cultivation, and to a higher extent by cultivation and addition of IL-1beta, TNF-alpha, TGF-beta or A23187. Downregulation of c-kit occurred in the presence of SCF or PMA. SCF caused a downregulation of c-kit receptors in eight of nine, and a proliferative response in three of 11 c-kit-positive T-lymphoblastic cell preparations. We conclude that c-kit is able to transduce a growth stimulatory signal in some T-lymphoblastic cells and that its expression may not be detectable in a resting metabolic or proliferative state.     

Functional capabilities of molecular network components controlling the mammalian G1/S cell cycle phase transition

The molecular interactions implicated in the mammalian G1/S cell cycle phase transition comprise a highly nonlinear network which can produce seemingly paradoxical results and make intuitive interpretations unreliable. A new approach to this problem is presented, consisting of (1) a convention of unambiguous reaction diagrams, (2) a convenient computer simulation method, and (3) a quasi-evolutionary method of probing the functional capabilities of simplified components of the network. Simulations were carried out for a sequence of hypothetical primordial systems, beginning with the simplest plausibly functional system. The complexity of the system was then increased in small steps, such that functionality was added at each step. The results suggested new functional concepts: (1) Rb-family proteins could store E2F in a manner analogous to the way a condenser stores electric charge, and, upon phosphorylation, release a large wave of active E2F; (2) excessive or premature cyclin-dependent kinase activities could paradoxically impair E2F activity during the G1/S transition period. The results show how network simulations, carried out by means of the methods described, can assist in the design and interpretation of experiments probing the control of the G1/S phase transition.     

Calcium modulation of activation and desensitization of nicotinic receptors from mouse brain

The effects of extracellular calcium on functional properties of nicotinic receptors from mouse thalamus were investigated. Previous studies have reported that calcium modulates the function of several neuronal nicotinic receptors. A 86Rb+ ion efflux assay was developed to measure nicotinic receptor function from brain tissue, and data indicate that alpha4beta2 receptors may mediate this response. Using the 86Rb+ efflux assay, calcium effects on receptor activation, desensitization induced by high, activating and low, subactivating concentrations of agonist, and recovery from desensitization were examined. Effects of calcium on the kinetics of ligand binding were also investigated. Calcium modulated receptor activation by increasing the maximal response to nicotine in a concentration-dependent manner, without affecting the EC50 of nicotine. Barium, but not magnesium, mimicked the effects of calcium on receptor activation. The increase in receptor activation could not be explained by changes in the ratio of activatable to desensitized receptors as assessed by the kinetics of ligand binding. Desensitization following activation was unaffected by calcium. Calcium, barium, and magnesium, however, increased the potency of nicotine for desensitization induced by exposure to low, subactivating concentrations of nicotine. Recovery from desensitization was not modulated by calcium. These data suggest that calcium modulates various functional aspects of nicotinic receptors from mouse brain and may do so via different mechanisms.     

Echocardiographic follow-up of diphtheric myocarditis

Factors affecting the postoperative ambulatory state of patients with intraspinal neurilemomas and meningiomas were evaluated in 92 patients who underwent surgery at the Chang Gung Memoriam Hospital. The patients' records were reviewed retrospectively and leg power grading was noted (Medical Research Council of Great Britain grading system, zero to five). Of the 89 patients with a preoperative leg power of 1 or better, 87 could walk with or without aids shortly after surgery. The remaining three patients, with a preoperative leg power of zero, were all wheelchair-bound postoperatively. The presence of sensory deficits and sphincter incontinence did not correlates with a poor postoperative ambulatory state, provided the preoperative leg power was above zero. The average period between the onset of the earliest symptoms and the establishment of the diagnosis was 68 weeks for patients with intraspinal neurilemomas and 71 weeks for those with meningiomas. Surgical for patients with neurilemomas were as good as those with meningiomas. Patients with multiple spinal neurilemomas did not fare any worse after surgery.     

Calcipotriol toxicity in a dog

The article describes the objectives and design of a prospective study of the prevalence, incidence and course of psychiatric disorders in a representative sample of non-institutionalized Dutch adults. A total of 7146 men and women aged 18-64, contacted through a multistage sample of municipalities and households, were interviewed at home in 1996. The primary diagnostic instrument was the CIDI, which determines the lifetime occurrence of DSM-III-R disorders. The disorders included were: mood disorders, anxiety disorders, eating disorders, schizophrenia and other non-affective psychotic disorders, and dependence and abuse of psychoactive substances. Follow-up measurements in the same sample were scheduled at 12 and 36 months. The net response to the first measurement was 69.7%. Poststratification weightings were applied for gender, age, marital status and degree of urbanization. Limitations and advantages of the study design are discussed. Findings are reported elsewhere in this issue.     

Formation of octa- and heptachlorodibenzo-p-dioxins during semi anaerobic digestion of sewage sludge

Octa- and heptachlorodibenzo-p-dioxins (OCDD and HpCDD) were formed during semi anaerobic digestion of sewage sludge at low temperature (20 degrees C). A twofold increase of OCDD and HpCDD was found after a digestion period of 192 days even if concentrations were corrected by corresponding accumulation factors caused by the degradation of biomass. Other polychlorinated dibenzo-p-dioxins and furans (PCDD/F) and polychlorinated biphenyls (PCB) were not increased. Under strictly anaerobic and aerobic conditions, however, no OCDD and HpCDD were formed. Semi anaerobic formation of OCDD and HpCDD may explain the prevalence of higher chlorinated PCDD in the homologues pattern typical for sewage sludge.     

Group B Streptococcal septicaemia/meningitis in neonates in a Singapore teaching hospital

Several studies have indicated that frequent allelic losses in some specific chromosomal regions occur during colorectal cancer (CRC) progression. To clarify the correlation between such allelic losses and metastatic potential, the allelotype of lymph node-positive early CRCs, which are small but extremely malignant cancers consisting of metastatically competent cells, were investigated. Nineteen paraffin-embedded specimens of early CRC (pT1 tumors according to TNM classification) with positive lymph nodes were collected. The tumor tissues were examined for loss of heterozygosity (LOH), using microsatellite markers on chromosomes 1p34-36, 8p21-22, 14q32, 18q21 and 22q12-13. The relationship between p53 protein expression and the metastatic status was also investigated by immunohistochemical staining. A group of 20 early CRCs with negative lymph nodes having a similar distribution of macroscopic appearance were used as controls. Among the 19 node-positive tumors, LOH at 8p21-22 and 18q21 was detected in 11 cases (57.9%) and 17 cases (89.4%), respectively. Allelic losses within these 2 regions in node-positive tumors were significantly more frequent than that in node-negative ones (p < 0.01). No significant correlation was found between LOH at 1p34-36, 14q32 or 22q12-13 and lymph node metastasis. p53 protein expression was not significantly associated with lymph node metastasis. Our results suggest that putative tumor suppressor genes, which may be involved in the metastatic process of CRC, are located on chromosomes 8p21-22 and 18q21. Allelic losses in these regions are possible risk factors for lymph node metastasis of early CRC.