Variability of clinical and pressure-flow study variables after 6 months of watchful waiting in patients with lower urinary tract symptoms and benign prostatic enlargement

PURPOSE: We quantified the physiological variability of clinical and pressure-flow study variables in patients with symptomatic benign prostatic enlargement. MATERIALS AND METHODS: Symptom scores were measured, and advanced urodynamic studies with pressure-flow analysis were performed in 178 patients before and 6 months after a period a watchful waiting. RESULTS: Patients without bladder outlet obstruction experienced significant symptomatic improvement. Symptoms in patients with obvious bladder outlet obstruction did not improve significantly. The reproducibility of mean pressure-flow variables was evident. However, there was an important intra-individual variability. Patients with obvious bladder outlet obstruction showed a significant decreases in detrusor pressure at maximal flow of 14cm. water, a significant decrease in the urethral resistance factor of 7 cm. water and a significant decrease of 1 obstruction class on the linear passive urethral resistance relation nomogram, indicating less severe bladder outlet obstruction. CONCLUSIONS: Mean differences among therapy groups must be regarded critically, especially when the difference are slight and possibly within physiological variability.     

Concurrent right diaphragmatic hernia and esophageal atresia

The occurrence of a coexisting congenital diaphragmatic hernia (CDH) and esophageal atresia (EA) with distal tracheoesophageal fistula is extremely rare and is considered highly lethal. Only 19 cases of CDH with EA have been reported in the world literature to date. This is a very challenging clinical problem, and the neonate is likely to deteriorate rapidly. Such a case is reported with a successful outcome, probably the first survivor with a right CDH and EA. Management guidelines for such a case are discussed.     

The role of glycoproteins gC, gE, gI, and gG in the induction of cell-mediated immune responses to bovine herpesvirus 1

Mutant viruses with deletions in genes encoding non-essential glycoproteins are considered as promising bovine herpesvirus 1 (BHV1) vaccine candidates. The present study compared the influence of various gene deletions (gC, gE, gI, gG) on the induction of cell-mediated immune responses against the virus. The highest BHV1 specific lymphoproliferative response was observed in the group of calves inoculated with the gC- mutant. However, in all groups of inoculated calves, limiting dilution analysis showed marked individual variability in the number of BHV1 specific T lymphocytes that were stimulated. The same animals were then challenged with wild-type BHV1. In these animals, limiting dilution analysis did not reveal gE, gI nor gG as a major T lymphocyte antigen. However, further analysis suggested the T cell antigenicity of gE in a low number of BHV1 hyperimmunized calves. Stimulation of MHC unrestricted cytotoxicity was also evaluated after inoculation with the various deletion mutants. Cytotoxicity in gC- inoculated calves was as high as in BHV1 inoculated calves. In conclusion, among the BHV1 deletion mutants that were tested, the gC- mutant stimulated the best cell-mediated immune responses.     

Implications of Deltatheridium specimens for early marsupial history

We describe here two new specimens of the mammal Deltatheridium pretrituberculare from the Late Cretaceous period of Mongolia. These specimens provide information on tooth replacement in basal therian mammals and on lower jaw and basicranial morphology. Deltatheroidans, known previously from isolated teeth, partial rostra and jaws from the late Cretaceous of Asia and possibly North America, have been identified variously as eutherians, as basal metatherians (the stem-based clade formed by marsupials and their extinct relatives), or as an outgroup to both eutherians and metatherians. Resolution of these conflicting hypotheses and understanding of the early evolution of the therian lineage have been hampered by a sparse fossil record for basal therians. The new evidence supports metatherian affinities for deltatheroidans and allows a comprehensive phylogenetic analysis of basal metatherians and marsupials. The presence of specialized marsupial patterns of tooth replacement and cranial vascularization in Deltatheridium and the basal phylogenetic position of this taxon indicate that these features are characteristic of Metatheria as a whole. Other morphological transformations recognized here secure the previously elusive diagnosis of Metatheria. The new specimens of Deltatheridium illustrate the effectiveness of fairly complete fossil specimens in determining the nature of early evolutionary events.     

Random mutagenesis of the cAMP chemoattractant receptor, cAR1, of Dictyostelium. Evidence for multiple states of activation

cAMP receptor 1 (cAR1) of Dictyostelium couples to the G protein G2 to mediate activation of adenylyl and guanylyl cyclases, chemotaxis, and cell aggregation. Other cAR1-dependent events, including receptor phosphorylation and influx of extracellular Ca2+, do not require G proteins. To further characterize signal transduction through cAR1, we performed random mutagenesis of the third intracellular loop (24 amino acids), since the corresponding region of other seven helix receptors has been implicated in the coupling to G proteins. Mutant receptors were expressed in car1(-) cells and were characterized for G protein-dependent and -independent signal transduction. Our results demonstrate that cAR1 is remarkably tolerant to amino acid substitutions in the third intracellular loop. Of the 21 positions where amino acid substitutions were observed, one or more replacements were found that retained full biological function. However, certain alterations resulted in receptors with reduced ability to bind cAMP and/or transduce signals. There were specific signal transduction mutants that could undergo cAMP-dependent cAR1 phosphorylation but were impaired either in coupling to G proteins, in G protein-independent Ca2+ influx, or in both pathways. In addition, there were general activation mutants that failed to restore aggregation to car1(-) cells and displayed severe defects in all signal transduction events, including the most robust response, cAMP-dependent cAR1 phosphorylation. Certain of these mutant phenotypes were obtained in a complementary study, where the entire region of cAR1 from the third to the seventh transmembrane helices was randomly mutagenized. Considered together, these studies indicate that the activation cycle of cAR1 may involve a number of distinct receptor intermediates. A model of G protein-dependent and -independent signal transduction through cAR1 is discussed.     

Effect of an enzymatic rinse on salivary levels of Streptococcus mutans and lactobacilli in periodontally treated patients

Root surface caries is prevalent in patients with both treated and untreated periodontal disease. The major etiologic factor has been identified as microbial plaque. In periodontally treated patients, significantly higher root caries prevalence and incidence have been found in patients with high levels of Streptococcus mutans and Lactobacilli in saliva. Reducing the levels of S. mutans and Lactobacilli in saliva may lower the risk of root caries development. The purpose of this investigation was to determine the effect of an oral enzymatic rinse on the salivary counts of S. mutans and Lactobacilli in periodontally treated patients. Fifteen adult subjects participated in a double-blind, cross-over designed clinical trial. Each subject had previously undergone comprehensive periodontal therapy and had been maintained on a regular program of supportive periodontal therapy. Paraffin-stimulated whole saliva was collected from each participant. Each subject was then randomly given either the enzymatic rinse product or a control rinse and instructed to rinse with one tablespoonful twice a day for 2 weeks, after which saliva samples were taken. After a washout period, salivary samples were again taken, and the subjects received the alternate rinse product. Two weeks later, final salivary samples were taken. The salivary samples were serially diluted and incubated aerobically on selective culture media. S. mutans and Lactobacilli were counted on the basis of colonial morphology. Pretreatment and posttreatment salivary counts of S. mutans and Lactobacilli were analyzed using the Wilcoxon matched-pairs signed-rank test at the 5% level of significance. Analysis of data revealed that neither the test nor the control rinse significantly lowered salivary counts of either species in the sample population.     

Transglutaminase II: a new class of GTP-binding protein with new biological functions

Tissue type transglutaminase (TGase II) is historically a member of the transglutaminase family, which covalently cross-links cellular proteins and polyamines. A recent new finding in the TGase II field is that the enzyme functions as a signal mediator from receptors to an effector in transmembrane signaling. This review will discuss the recent development of TGase II. This new signal transducer was termed Gh when initially discovered and was recently found to be TGase II. To help the reader understand the role of Gh as a signal mediator, the role of heterotrimeric G-proteins in hormone-mediated transmembrane signaling is briefly discussed. We have highlighted how Gh transmits the alpha 1-adrenoceptor signal to the phospholipase C-delta 1 and how Gh is activated and deactivated compared to the prototype of heterotrimeric G-proteins. Recent developments regarding the structure-function of Gh and other biological functions of Gh are discussed to facilitate understanding the impact of Gh in cells.     

The effects of colony-stimulating factor-1 on the number and ultrastructure of osteoclasts in toothless (tl) rats and osteopetrotic (op) mice

The role of colony-stimulating factor-1 (CSF-1 or M-CSF) in osteoclast development is illustrated by observations that administration of exogenous CSF-1 increases osteoclast number and improves the skeletal sclerosis of two osteopetrotic mutations, toothless (tl) in the rat and osteopetrotic (op) in the mouse. We examined the effects of CSF-1 treatment on the number and ultrastructure of osteoclasts in the tibial metaphysis of normal and mutant animals of both stocks to understand the similarities and differences between these two mutations. Osteoclasts from normal animals of both stocks were abundant and possessed the ultrastructural features of active cells. These included apical areas in contact with mineralized surfaces with tightly apposed clear zones, extensive ruffled borders, and a vacuolated cytoplasm with numerous mitochondria. In toothless rats osteoclasts were difficult to locate and those present had poorly defined ruffled borders, fewer cytoplasmic vacuoles, and a basal membrane with both smooth and ruffled areas. Large lipid accumulations were often found near tl osteoclasts. Osteoclasts in op mice were difficult to find, but more numerous than in tl rats. Unlike tl osteoclasts, those of op mice possessed very well developed ruffled borders, small clear zones, and large electron-dense cytoplasmic inclusions. These cells also had unusual basal membranes with both smooth and ruffled regions. CSF-1 treatment increased the number of osteoclasts in both mutant stocks, normalizing the numbers in op mice, but not tl rats. CSF-1 injections caused dramatic changes in the morphology of tl osteoclasts, including increased incidence and size of ruffled borders and cytoplasmic vacuolization. The growth factor had little effect on ruffled borders or clear zones in op mice. Interestingly, mutant osteoclasts of both stocks exhibited a ruffled basal membrane in response to CSF-1 treatment. This increase in membrane ruffling may reflect the ability of CSF-1 to promote rapid formation of osteoclasts from mononuclear precursors in a more permissive microenvironment. Our data indicate that CSF-1 is not required for the development of at least some osteoclasts. The differences in response to CSF-1 treatment which we report lead us to speculate that additional factors may be involved in osteoclastogenesis.