Duplication of the urethra

Ten patients with patent urethral duplication are presented. Nine patients had two independent patient channels originating from the bladder or the posterior urethra. Both voiding cystourethro and retrograde urethrography are necessary to completely evaluate this anomaly. In each instance the ventral channel, regardless of the position of its meatus, proved to be the more functional urethra. In those patients whose dorsal channel was in an epispadiac position, the symphysis pubis was abnormally wide. A functionally and anatomically accurate classification is proposed, and the embryology of these anomalies is discussed.     

Peripheral nerve glycoproteins and myelin fine structure during development of rat sciatic nerve

Developmental changes in relative amounts of peripheral nerve proteins and glycoproteins have been correlated with the degree of morphological myelination at various ages during the first 25 postnatal days in rat sciatic nerve. At birth there is virtually no major myelin glycoprotein (P0), but there is a protein which migrates to the same point on sodium dodecyl sulphate (SDS) polyacrylamide gels as the small myelin basic protein (P2). During the time myelin is being formed in the nerve, the P0 protein increases and the P2 protein appears to decrease in relative amount in the nerve. The accumulation of P0 protein in the nerve correlates extremely well with the degree of myelination in sciatic nerve. At 4-6 days postnatal, smooth membrane profiles are observed which are located within axons and in the inner Schwann cell cytoplasm. Such profiles are also observed to fuse with the axolemma-Schwann cell interface. The profiles may represent membrane material being added to or deleted from the axolemma or myelin during myelination.     

Characterization of fractionated human diploid fibroblast cell populations

In a series of 1334 consecutive pneumoencephalographies in children 0-15 years, there were 2 deaths, 3 severe apneas and 1 pneumomediastinum. Respiratory insufficiency, due to contention of the patient with resulting impairment of the motion of thoracic muscles was an important mechanism and pneumoencephalography is contra-indicated in children with respiratory difficulties prior to the examination. In 90 consecutive patients submitted to pneymoencephalography CSF changes and fundus oculi abnormalities were studied prospectively. Aseptic meningitis of a mild degree is common following the examination, whereas significant meningeal haemorrhage is rare. Haemorrhages in the fundi were noted in 10% of the patients. The general tolerance of the examination was good.     

Inhibition of GABAA receptor function by tyrosine kinase inhibitors and their inactive analogues

The effects of tyrosine kinase inhibitors which target the ATP binding site or the substrate binding site of tyrosine kinases were assessed on murine recombinant type A gamma-aminobutyric acid (GABAA) receptors expressed in Xenopus oocytes or HEK cells using two-electrode voltage clamp or patch clamp recording. Genistein inhibited in a noncompetitive manner GABA-activated currents recorded from alpha1beta1gamma2S receptor constructs by reducing the maximum normalized response from 1.83 +/- 0.04 to 0.71 +/- 0.04 and reducing the EC50 from 35.7 +/- 2.1 microM to 15.1 +/- 3.9 microM. After mutating the two "functionally active" substrate tyrosine (Y) residues in gamma2S and expressing the mutant receptor alpha1beta1gamma2S(Y365F, Y367F), genistein still noncompetitively inhibited the responses to GABA reducing the maximum current from 1. 81 +/- 0.03 to 0.26 +/- 0.01 and the EC50 from 33.1 +/- 2.3 microM to 5.8 +/- 2.2 microM. The inactive compound, daidzein, also similarly inhibited responses to GABA on these two receptor constructs. Inhibitors targeting the substrate binding site of tyrosine kinases, the tyrphostins, also inhibited both the wild-type and the tyrosine mutant GABAA receptors. Tyrphostin A25 and the inactive tyrphostin A1 reduced the maximum normalized responses for alpha1beta1gamma2S and alpha1beta1gamma2S(Y365F, Y367F) receptors by 73 and 64%, respectively. The tyrosine kinase inhibitors and their inactive controls did not display any significant voltage sensitivity to the antagonism of GABA-activated responses. Moreover, genistein or tyrphostin A25 did not affect the potentiation of responses to GABA by pentobarbitone or diazepam. Mutating the two "functionally silent" tyrosine residues, Y370 and Y372, known to be substrates for tyrosine kinases in the beta1 subunit and coexpression in the alpha1beta1(Y370F, Y372F)gamma2S(Y365F, Y367F) construct failed to affect the inhibitory action of genistein. The study concludes that tyrosine kinase inhibitors and their inactive controls can directly interact with GABAA receptors completely independent of any effects on tyrosine kinases.     

Effect of estradiol-17 beta on basal and hCG stimulated progesterone secretion by porcine luteal cells isolated in various stages of the luteal phase

T cells of mice display V beta-specific reactivity for a spectrum of mouse mammary tumor virus (Mtv) antigens; confrontation with these antigens during ontogeny causes substantial "holes" in the T cell repertoire. Since endogenous Mtv antigens are rare in other species, the question arises whether V beta-specific recognition of Mtv antigens is unique to mice. To examine this question, rat T cells were allowed to differentiate from stem cells in severe combined immunodeficiency (SCID) mice. These rat-->mouse xenochimeras were prepared under a variety of conditions. The results show that rat T cells are strongly reactive to mouse Mtv antigens, both in terms of tolerogenicity and immunogenicity. In fact, the V beta specificity of rat and mouse T cells for Mtv antigens is almost indistinguishable.     

Variants of tissue-type plasminogen activator which display substantially enhanced stimulation by fibrin

Unlike most proteases, tissue-type plasminogen activator (t-PA) is secreted from cells as an active, single chain "proenzyme" whose catalytic efficiency is comparable with that of the corresponding mature, two-chain enzyme. We have previously suggested that the absence of the "zymogen triad" (Asp194-His40-Ser32; chymotrypsin numbering) contributes to this unusually high enzymatic activity of single chain t-PA. Consistent with this prediction, the single chain form of a variant of t-PA containing the zymogen triad displayed dramatically reduced activity toward synthetic substrates. Activation cleavage of this variant, however, resulted in a mature, two-chain enzyme with full catalytic activity. To further examine the functional significance of the zymogen triad, we used site-specific mutagenesis to construct a variant of t-PA, t-PA/R275E,A292S,F305H, that contained this triad but could not be converted into its two-chain form by plasmin. Characterization of this variant demonstrated that the presence of the zymogen triad specifically suppressed plasminogen activation by single chain t-PA in the absence of fibrin. In addition, these studies indicated that, like wild type t-PA, zymogen activation of this variant could be accomplished by binding to the co-factor fibrin. The combination of full activity in the presence of fibrin and reduced activity in its absence resulted in novel variants of t-PA that displayed dramatically enhanced stimulation by fibrin. While the presence of fibrin increased the catalytic efficiency of t-PA toward plasminogen by a factor of approximately 520, this stimulation factor increased to 130,000 for t-PA/R275E,A292S,F305H. Plasmin-resistant, zymogen-like variants of t-PA, therefore, may represent thrombolytic enzymes with enhanced "clot selectivity."     

Public release of cardiac surgery outcomes data in New York: what do New York state cardiologists think of it?

BACKGROUND AND OBJECTIVE: Since 1990, risk-adjusted outcomes for patients undergoing coronary artery bypass graft surgery in New York state have been released to the public. The purpose of this study was to assess the extent to which referring cardiologists share these data with patients and use these data to make referrals. METHODS: A survey questionnaire was sent to all cardiologists in New York in the New York State Chapter of the American College of Cardiology. RESULTS: Four hundred fifty cardiologists responded to the survey. Most (94%) found the report "easy to read." A majority (67%) found the report to be "very accurate" or "somewhat accurate" in capturing differences in the performance of cardiac surgeons, whereas 33% found it to be "not at all accurate." Twenty-two percent reported that they "routinely discuss the reports with their patients," and 38% responded that the information has affected their referrals to surgeons "very much" or "somewhat." CONCLUSIONS: A majority of cardiologists has not generally changed their well-established referral patterns as a result of the New York coronary artery bypass graft surgery reports. However, there has been a modest impact on referrals resulting from the distribution of these reports. The findings also suggest that increased dialogue between clinicians and policy makers regarding the format and structure of public releases would be a valuable undertaking.     

Intramuscular clindamycin for therapy of infective endocarditis. Report of 23 cases and review of the literature

Twenty-three patients with infective endocarditis received intramuscular clindamycin (Cleocin) for treatment. Thirteen had acute Staphylococcus (S.) aureus endocarditis but none had involvement of the aortic valve. Eleven of these 13 infections were heroin-related and involved the tricuspid valve.Twenty-one patients were successfully treated. Two patients with heroin-related S. aureus infection failed to respond to intramuscularly administered clindamycin, but responded to retreatment with methicillin. There have been 34 reported cases of endocarditis treated with clindamycin. Although 80 percent of all cases due to staphylococci responded favorably, almost all were heroin-related tricuspid valve infections. In addition 91 percent of cases due to aerobic streptococci responded but, surpisingly, treatment failed in three of four cases of anaerobic endocarditis. Although clindamycin can be useful in streptococcal endocarditis and in some cases of heroin-related S. aureus tricuspid endocarditis, caution should be exercised in its use. It is "less" bactericidal than the penicillins or cephalosporins, and organisms have become resistant during treatment. Furthermore, patients with anaerobic endocarditis have not responded well, and data are not available to recommend administration of clindamycin for acute S. aureus infections engrafted on the aortic or mitral valve.