The cdc2-related protein p40MO15 is the catalytic subunit of a protein kinase that can activate p33cdk2 and p34cdc2

Activation of the cyclin-dependent protein kinases p34cdc2 and p33cdk2 requires binding with a cyclin partner and phosphorylation on the first threonine residue in the sequence THEVVTLWYRAPE. We present evidence that this threonine residue, number 160 in p33cdk2, can be specifically phosphorylated by a cdc2-related protein kinase from Xenopus oocytes called p40MO15. Binding to cyclin A and phosphorylation of this threonine are both required to activate fully the histone H1 kinase activity of p33cdk2. In cell extracts, a portion of p40MO15 is found in a high molecular weight complex that is considerably more active than a lower molecular weight form. Wild-type MO15 protein expressed in bacteria does not possess kinase activity, but acquires p33cdk2-T160 kinase activity after incubation with cell extract and ATP. We conclude that p40MO15 corresponds to CAK (cdc2/cdk2 activating kinase) and speculate that, like p33cdk2 and p34cdc2, p40MO15 requires activation by phosphorylation and association with a companion subunit.     

Priapism: etiology and management

Priapism is a urologic emergency. All patients should receive prompt urologic consultation. Management is based on prompt recognition, differentiation between low- and high-flow priapism, reversal of any potential precipitating factors, and the use of corporal aspiration/irrigation combined with intracavernosal alpha-agonist injection therapy. It cannot be over-emphasized that severely prolonged erections are associated with the development of irreversible problems with erectile function and, therefore, immediate and aggressive management is mandatory.     

Pseudotumor form of pulmonary nocardia infection (Nocardia nova) in a renal transplant patient

The authors report a case of pulmonary nocardiosis due to Nocardia nova occurring in a smoker who had a renal transplant. A pseudo-tumour was found on a standard X-ray and computerised tomography did not suggest the diagnosis. Needle aspiration under computerised tomographic control enabled a diagnosis to be made.     

Paratesticular rhabdomyosarcoma in adult patients: 16-year experience at Institut Gustave-Roussy

BACKGROUND: Children with paratesticular rhabdomyosarcoma (RMS) have both a good prognosis and a high survival rate. The clinical behaviour and outcome of the disease in adults is not well described. PATIENTS AND METHODS: We reviewed retrospectively our experience with paratesticular RMS in patients older than 16 years during a 16-year period (1975-1991). RESULTS: Thirteen adult patients with paratesticular RMS are reported. Median age was 21 years (range 16 to 31). Presentation characteristics were scrotal mass in 11 cases, lumbar pain and weight loss in 5 cases, hypercalcemia in 3 cases and thrombocytopenia in 3 cases. There were 5 patients with stage IV, 2 with stage IIB and 6 with stage IA (IRS classification). The 5 stage IV patients are reported in detail, with initial bone marrow infiltration encountered in 4 of them. Objective response to chemotherapy was achieved in all 6 patients with measurable disease (2 CR + 4 PR). Two of 7 patients who received adjuvant chemotherapy relapsed at 7 and 11 months. After a median follow-up of 90 months, 8 patients (5 stage IV, 3 stage IA) died from disease progression. CONCLUSION: Metastatic disease with bone marrow involvement at presentation and aggressive behaviour seem to be more relevant in adult paratesticular RMS patients compared with children.     

Relative involvement of protein kinase C and of the estrogen receptor in the cytotoxic action of a population of triphenylethylenes on MCF7 cells as revealed by correspondence factorial (CF) analysis

A multivariate statistical method, correspondence factorial (CF) analysis, was used to examine the correlations among the protein binding and cell proliferation effects of a series of 36 di- and triphenylethylenes (DPEs and TPEs). The analysis was applied to a study which measured their competition for estradiol binding to cytosol estrogen receptor (ER), their influence on protein kinase C (PKC) activity under different conditions of enzyme activation, their ability to promote the growth of a breast cancer cell line and to inhibit growth at high concentrations (cytotoxicity). The CF analysis revealed several levels of correlation. First, it distinguished those molecules within the population that stimulated rather than inhibited PKC activity. Second, it made apparent a strong correlation between cytotoxicity and inhibition of Ca++ and phosphatidylserine-dependent PKC activity, which was most marked when the enzyme had been activated by diacylglycerol indicating that PKC inhibition under physiological conditions might contribute to the overall cytotoxicity of these compounds. Third, a lower level of correlation was established between competition for ER binding and cytotoxicity. Taken together, the results suggest that MCF7 cells might be most sensitive to a cytotoxic effect of TPEs (via PKC and other targets) when they at the same time decrease estrogen-stimulated proliferation via an ER-mediated antiestrogenic effect.     

Prednisolone therapy of idiopathic feline lower urinary tract disease: a double-blind clinical study

A double-blind clinical study was performed to evaluate prednisolone as treatment for idiopathic feline lower urinary tract disease. No differences in response were observed in prednisolone- and placebo-treated cats.     

Characterization of the chicken and quail homologues of the human gene responsible for the X-linked Kallmann syndrome

The human KAL gene, responsible for the X-linked Kallmann syndrome, was isolated previously. Southern blot analysis using human cDNA probes detected cross-hybridization with DNA from several organisms, including chicken and quail. The entire coding sequences of chicken and quail KAL cDNAs were determined. A comparison of these cDNAs with the human KAL cDNA reveals an overall identity of 73 and 72%, respectively. This results in 76 and 75% identity at the protein level. The highest conservation was found in the WAP four-disulfide core motif and in two of the four fibronectin type III repeats reported in the human protein. These results further support the hypothesis that the KAL protein is an extracellular matrix component with anti-protease and adhesion functions.     

Progressive scoliosis with vertebral rotation after lumbar intervertebral disc herniation in a 10-year-old girl

A case report of a 10-year old girl with a herniated disc is presented. The most significant symptoms were progressive scoliosis with a flat back and paravertebral muscle spasm. An absent H reflex on the left and an increased latency of the somatosensory-evoked potentials of the left posterior tibial nerve were found. The computed tomographic scan of the lumbar spine showed a large central left-sided disc protrusion at the L5-S1 level. Our case presents the youngest patient with documented intervertebral disc herniation and the only one with severe scoliosis and vertebral rotation. The curve was not structural because it improved with surgery and an orthosis was not necessary.     

Exceptional convergent evolution in a virus

Replicate lineages of the bacteriophage phiX 174 adapted to growth at high temperature on either of two hosts exhibited high rates of identical, independent substitutions. Typically, a dozen or more substitutions accumulated in the 5.4-kilobase genome during propagation. Across the entire data set of nine lineages, 119 independent substitutions occurred at 68 nucleotide sites. Over half of these substitutions, accounting for one third of the sites, were identical with substitutions in other lineages. Some convergent substitutions were specific to the host used for phage propagation, but others occurred across both hosts. Continued adaptation of an evolved phage at high temperature, but on the other host, led to additional changes that included reversions of previous substitutions. Phylogenetic reconstruction using the complete genome sequence not only failed to recover the correct evolutionary history because of these convergent changes, but the true history was rejected as being a significantly inferior fit to the data. Replicate lineages subjected to similar environmental challenges showed similar rates of substitution and similar rates of fitness improvement across corresponding times of adaptation. Substitution rates and fitness improvements were higher during the initial period of adaptation than during a later period, except when the host was changed.     

Interleukin 10 (IL-10) upregulates functional high affinity IL-2 receptors on normal and leukemic B lymphocytes

Interleukin 10 (IL-10) has recently been shown to induce normal human B lymphocytes to proliferate and differentiate into immunoglobulin (Ig)-secreting cells. Herein, we show that IL-10 also promotes DNA synthesis and IgM production by anti-CD40 activated B cell chronic lymphocytic leukemia (B-CLL). Most strikingly, IL-2 and IL-10 were found to synergize to induce the proliferation and differentiation of B-CLL cells. This synergy between IL-2 and IL-10 was also observed with normal B cells which proliferated strongly and secreted large amounts of IgM, IgG, and IgA. The observed synergy is likely to be due to the IL-10-induced increase of high affinity IL-2 receptors on both normal and leukemic B cells. This increase of high affinity receptor is associated to an increase of Tac/CD25 expression that can be detected by flow cytometric analysis. Taken together, these results indicate that IL-10 permits anti-CD40 activated B cells to respond to IL-2 through an induction of high affinity IL-2 receptors. This effect of IL-10 may partly explain how T cells, which activate B cells in a CD40-dependent fashion, induce B cell proliferation and differentiation mostly through IL-2.