The requirement of tyrosines 579 and 581 for maximal ligand-dependent activation of the betaPDGFR is influenced by noncytoplasmic regions of the receptor.

Mutating tyrosines 579 and 581 of the beta platelet-derived growth factor receptor (betaPDGFR) tyrosine kinase to phenylalanines (the F2 mutation) impair activation of the receptor in response to ligand, but mutation of the analogous tyrosines in the alphaPDGFR has no effect on ligand-dependent receptor activation. We have found that the F2 mutation has only a modest effect on ligand-dependent activation of a chimeric PDGFR composed of the extracellular and transmembrane domains of the alphaPDGFR and the cytoplasmic domain of the betaPDGFR by three measures: (1) the ability to phosphorylate endogenous and exogenous protein substrates in vitro, (2) phosphorylation of tyrosine 857, and (3) binding of the effector proteins PLCgamma, RasGAP, and SHP-2. Conversely, the F2 mutation substantially impairs ligand-dependent activation of chimeric PDGFRs that consist of either the extracellular domain alone or the extracellular and transmembrane domains of the betaPDGFR and all remaining sequence from the alphaPDGFR by two measures: (1) phosphorylation of endogenous protein substrates in vitro and (2) binding of PLCgamma and SHP-2. Our results indicate that the requirement of tyrosines 579 and 581 for maximal activation of the betaPDGFR in response to ligand is primarily determined by noncytoplasmic regions of the receptor.

Comparison of ultrasound imaging in patients undergoing transperineal and transrectal prostate ultrasound.

OBJECTIVES: Prostatic evaluation in men who have undergone prior abdominoperineal resection pose an unusual challenge for the urologist. Neither digital rectal examination nor transrectal ultrasound (TRUS) can be performed. Transperineal ultrasound (TPUS) has been suggested as an alternative means of imaging. This imaging modality was compared directly with the standard TRUS method. METHODS: TPUS was performed with a 4-MHz abdominal probe or biplane multiple frequency probe at a frequency of 5 to 7 MHz followed by TRUS at 7 MHz in 50 consecutive men referred for prostate ultrasound and biopsy who had not undergone prior abdominoperineal resection. Dimensions of the prostate and ultrasound findings such as hypoechoic, anechoic, or hyperechoic areas were noted for each sonographic approach. Volume calculation was performed by the prolate spheroid method. RESULTS: There was good TPUS visualization of the prostate in the transverse plane in 48 (96%) of 50 patients and in the sagittal plane in 45 (90%) of 50 patients. Prostate volume calculation by TPUS correlated well with the volume calculated by TRUS (r=0.876). Twenty-nine patients (58%) were found to have suspicious hypoechoic lesions by TRUS; none were seen by TPUS. Prostatic calcifications were present in 12 patients and were visualized by both TPUS and TRUS in all 12 patients. Six prostate glands demonstrated cystic lesions on TRUS imaging; three of these cystic lesions were also seen with TPUS imaging. CONCLUSIONS: TPUS allows visualization of the prostate with volume determination that is comparable to the volume determination by TRUS. Some intraprostatic findings such as calcifications and cysts can be identified; however, suspicious hypoechoic lesions were not identified by TPUS imaging of the prostate.

BRO1, a novel gene that interacts with components of the Pkc1p-mitogen-activated protein kinase pathway in Saccharomyces cerevisiae.

Yeast cells with mutations in BRO1 display phenotypes similar to those caused by deletion of BCK1, a gene encoding a MEK kinase that functions in a mitogen-activated protein kinase pathway mediating maintenance of cell integrity. bro1 cells exhibit a temperature-sensitive growth defect that is suppressed by the addition of osmotic stabilizers or Ca2+ to the growth medium or by additional copies of the BCK1 gene. At permissive temperatures, bro1 mutants are sensitive to caffeine and respond abnormally to nutrient limitation. A null mutation in BRO1 is synthetically lethal with null mutations in BCK1, MPK1, which encodes a mitogen-activated protein kinase that functions downstream of Bck1p, or PKC1, a gene encoding a protein kinase C homolog that activates Bck1p. Analysis of the isolated BRO1 gene revealed that it encodes a novel, 97-kDa polypeptide which contains a putative SH3 domain-binding motif and is homologous to a protein of unknown function in Caenorhabditis elegans.

Long-term experience with controlled expansion cylinders in the AMS 700CX inflatable penile prosthesis and comparison with earlier versions of the Scott inflatable penile prosthesis.

UNLABELLED: OBJECTIVEs. To determine complication and survival rates of the AMS 700CX penile prosthesis and to compare its reliability with earlier versions of the Scott inflatable penile prosthesis. METHODS: Retrospective chart review and telephone interviews were used. RESULTS: Actual 4-year survival of the AMS 700CX device was 85%, whereas earlier versions of the device had actual 4-year survival of 46% (p < 0.0001). The observed difference in prosthesis reliability could not be accounted for by differences in patient population, surgical technique, or incidence of infections. The most significant factor that contributed to improved prosthesis survival was the lack of cylinder complications (leaks and aneurysms). CONCLUSIONS: The controlled expansion cylinders of the AMS 700CX penile prosthesis are a significant advance in reliable, low-morbidity surgical therapy for impotence.

Medical therapy alone for the treatment of gas forming intrarenal abscess.

Gas forming renal infections are severe, potentially lethal conditions. Gas formation in an intrarenal abscess is extremely rare. Formerly, these patients were uniformly treated by a combined medical and surgical approach. We describe 2 patients with intrarenal gas abscess who were successfully treated with antibiotics alone. We review the literature concerning intrarenal gas abscess and propose a pathophysiological mechanism for its formation as well as a treatment schema.