Biomedical subjects
Publications and source records attributed to T Pham.
This article describes the use of the Jasper Jumper in the treatment of class III anomalies, both theoretically and with a case report. Contrary to its use in class II anomalies, the Jasper Jumper is fixed to the 6-year-molars in the lower jaw and in the canine area in the upper jaw. This results in a continuously working mechanism--independent of co-operation on the part of the patient.
OBJECTIVE: A select group of Escherichia coli strains known as uropathogenic cause pyelonephritis in nonpregnant individuals. We investigated whether Escherichia coli from gestational pyelonephritis represent a random population or possess common uropathogenic characteristics. STUDY DESIGN: Repetitive element sequence-based polymerase chain reaction, plasmid profiles, hemolysin, and O serotypes were assayed from Escherichia coli isolates of 57 pregnant patients with acute pyelonephritis at different gestational ages. RESULTS: The majority of the first trimester isolates fell primarily into repetitive element sequence-based patterns 1 and 3 and O6, O15, and O75 serotypes. Second-trimester isolates had multiple patterns with high-frequency repetitive element sequence-based polymerase chain reaction 1 and 5 and an unknown (OX) serotype. Pattern 3, predominantly O75 serotype, was found primarily among third-trimester isolates. CONCLUSION: It is likely that Escherichia coli associated with acute pyelonephritis during different trimesters of pregnancy represents nonrandom closely related isolates, and some of these strains may be characteristic in pregnant patients only.
The mouse is a common model for transgenic manipulation, however, their small size has made hemodynamic study difficult. A noninvasive 10-MHz pulsed Doppler probe was used to measure aortic and mitral flow velocities in anesthetized, intact mice to study the effects of aging and hypethyroidism (induced by thyroxine) one systolic and diastolic cardiac function. In 10 hyperthyroid mice peak aortic velocity (PAV, an index of systolic function) was 34% higher than in 10 control mice (108 +/- 2 vs. 80 +/- 3 cm/s, P < 0.05). The ratio of early to late mitral filling velocity (E/A ratio, an index of diastolic function) was 47% higher (5.6 +/- 0.8 vs. 3.8 +/- 0.2, P < 0.05) in the hyperthyroid mice. In six old (30 mo) mice PAV was similar to eight young (4 mo) mice (73 +/- 3 vs. 75 +/- 3 cm/s), but the E/A ratio was 59% lower (1.8 +/- 0.3 vs. 4.4 +/- 0.4, P < 0.05). Despite a wide range of observed heart rates, the systolic and diastolic parameters of the groups were clearly separated. We conclude that cardiac systolic and diastolic function in mice, measured by pulsed Doppler ultrasound, are similar to larger species both in magnitude and in their response to hyperthyroidism and aging.
Congenital decubital ulcers were found in 94% of newborn infants with unilateral cleft lip and palate in the course of a systematic study of a large cohort study (N = 52). The procedures for diagnosis, documentation, and follow-up are described. The ulceration area at birth varied over a wide range. The ulcerations were usually located in the posterior part of the vomer. Sonographic evidence supports the hypothesis that the ulcerations are caused mechanically by the motor activity of the tongue during the fetal and newborn period. The decubital ulcer disappeared in each case within 5 days following the implementation of a palatal plate.
Several clinical isolates of Serratia marcescens were found to dissociate on peptone glycerol agar into colonies with red and pink or white and gray phenotypes that differ in the expression of proteolytic activity and mannose-sensitive type of hemagglutination. Colonies of red and white type were proteolytically active but did not express hemagglutination, whereas pink and gray colonies were protease-deficient but agglutinated guinea pig erythrocytes. Site-directed mutagenesis of a red laboratory strain S. marcescens SM6 resulted in selection of protease negative derivative prt::G7 which expressed the pink phenotype with hemagglutinating activity. It is suggested that a DNA-regulatory element may be involved in this type of colony variation.
We investigated the hemolytic activity of Escherichia coli strain EC901 carrying plasmid pBJN406 containing genes draA-E involved in expression of the mannose-resistant Dr hemagglutinin, and in its isogenic insertion mutants devised with Tn5, Tn3, and TnphoA. While E. coli BN406 displayed rapid hemolytic activity against equine erythrocytes, insertion mutations in draD and draE, but not in draA, draB, and draC, abolished all hemolytic activity. These data suggest a role for draD and draE in the expression of hemolysis.
A low molecular weight endogenous substance believed to be responsible for extracellular fluid homeostasis in mammals has been sought for many years. Our goal is to isolate and structurally characterize this putative "natriuretic hormone." We have developed an assay using the conscious rat to measure prolonged natriuresis (Benaksas et al (1993) Life Sciences, 52, 1045-1054), the activity originally described for this putative substance. Using this assay we have identified a number of natriuretic compounds isolated from human uremic urine. The collected urine is processed by ultrafiltration (< or = 3 kDa), gel filtration chromatography (G-25) and extraction with isopropanol and diethyl ether. The organic soluble material is then subjected to sequential high-performance liquid chromatography. We report here the initial characterization of two pure isolates (LLU-alpha and LLU-gamma) obtained by this method, and the structural elucidation of a third pure compound, LLU-beta 1, a natriuretic and previously unreported metabolite of the drug diltiazem.
Bacterial adhesins are important virulence factors that allow colonization of the human urogenital tract by Escherichia coli. Adhesins of the Dr family have been found to be more frequently expressed in strains associated with symptomatic urinary tract infections. Because of the high frequency of symptomatic urinary tract infections during pregnancy, we screened E. coli isolates from 64 gestational pyelonephritis patients for the expression of Dr and X adhesins to address their potential virulence roles in this population. Using PCR and primers for the afaB gene, we detected dra-related operons in 17 isolates (27%). On the basis of the lack of hemagglutination of Dr(a-) erythrocytes containing a point mutation in the decay-accelerating factor (DAF) short consensus repeat-3 (SCR-3) domain, 12 of these strains were categorized as classical Dr adhesins. The hemagglutination of O erythrocytes by Dr+ strains was blocked or reduced by a monoclonal antibody to the DAF SCR-3 domain. The remaining five dra-positive strains agglutinated Dr(a-) erythrocytes. Monoclonal antibody to the DAF SCR-3 domain failed to block O-erythrocyte hemagglutination. Adhesins in these strains did not fulfill criteria for Dr hemagglutinins because of the undefined receptor specificities and were categorized as X. E. coli strains bearing dra-related X adhesins bound to DAF cDNA-transfected Chinese hamster ovary cells. Three of these dra-related X-adhesin-bearing E. coli strains failed to attach to the SCR-3 delta deletion transfectant, which suggested that binding sites were located in the SCR-3 domain but outside the region blocked by the monoclonal anti-SCR-3 immunoglobulin G. The binding sites of the remaining two dra-related X adhesin strains were localized to the SCR-4 domain, as the attachment was shown to be abolished on an SCR-4 delta mutant but unaffected by an SCR-3 delta deletion. The heterogeneity in the binding sites of E. coli DAF (Dr) family adhesins from gestational pyelonephritis isolates may reflect the ability of the adhesins to evolve to recognize alternate peptide epitopes for efficient colonization.
Transforming growth factor beta (TGF-beta), a potent regulator of bone formation, has bifunctional effects on osteoblast replication and biochemical activity that appear differentiation dependent. We now show that cell surface binding sites for TGF-beta vary markedly among fibroblasts, bone-derived cells, and highly differentiated osteosarcoma cultures from fetal rats. Expression of betaglycan and type II receptors decline relative to type I receptor expression in parallel with an increase in osteoblast-like activity, predicting that the ratio among various TGF-beta binding sites could influence how its signals are perceived. Bone morphogenetic protein 2 (BMP-2), which induces osteoblast function, does not alter TGF-beta binding or biochemical activity in fibroblasts and has only small effects in less differentiated bone cells. In contrast, BMP-2 rapidly reduces TGF-beta binding to betaglycan and type II receptors in osteoblast-enriched primary cell cultures and increases its relative binding to type I receptors in these cells and in ROS 17/2.8 cultures. Pretreatment with BMP-2 diminishes TGF-beta-induced DNA synthesis in osteoblast-enriched cultures but synergistically enhances its stimulatory effects on either collagen synthesis or alkaline phosphatase activity, depending on the present state of bone cell differentiation. Therefore, BMP-2 shifts the TGF-beta binding profile on bone cells in ways that are consistent with progressive expression of osteoblast phenotype, and these changes distinguish the biochemical effects mediated by each receptor. Our observations indicate specific stepwise actions by TGF-beta family members during osteoblast differentiation, developing in part from changes imprinted by BMP-2 on TGF-beta receptor stoichiometry.
Explore the source record for details and available documents.
Treatment with the non-competitive NMDA receptor blocker MK-801 (0.16 mg/kg), given to juvenile rats before and after the exposure to an enriched environment on alternate days for 4 weeks, attenuated the improvements in spatial learning and open field adaptation which resulted from such environmental stimulation. Drug treatment affected the consolidation of experiences as an injection given after exposure to the enriched environment was needed to demonstrate this effect. In addition, MK-801 administration diminished the adverse effect of stimulus deprivation-the slow learning rate normally seen in rats housed in impoverished environment. Radioligand binding studies showed that drug treatment decreased [3H]MK-801 binding sites in cortex. The learning, activity and receptor binding effects were measured 4 months from cessation of the drug treatment and environmental manipulation. The results support the role of NMDA receptors in mediating cognitive changes associated with environmental stimulation.
It is our purpose to isolate and characterize the putative "Natriuretic Hormone", ostensibly responsible for ECF homeostasis, as well as identify endogenous pressors and compounds that induce prolonged natriuresis; we report here our initial progress in this area. Large volumes of pooled urine collected from uremic patients were fractionated, and the resulting isolates were evaluated for in vivo natriuretic and pressor effects and Na+/K(+)-ATPase inhibitory activity in renal cells. The purification steps involved ultrafiltration to obtain materials of less than 3000 da, gel filtration, and sequential reversed-phase high performance liquid chromatography (HPLC). After each HPLC step, the fractions were evaluated for their ability to elicit significant natriuresis and/or influence mean arterial pressure in the normal conscious female rat. Each fraction was also assayed for its ability to inhibit Na+/K(+)-ATPase as determined by the inhibition of 86Rb+ uptake into MDBK renal cells. While several of the fractions elicited profound natriuresis and/or pressor activity and other fractions inhibited Na+/K(+)-ATPase, there was no correlation among the activities in individual fractions. We have concluded that this plethora of bioactivities is responsible for much of the confusion and multiplicity of crude isolates claimed to be the putative hormone. Presently we are attempting to purify each of these activities to chemical homogeneity for structure determination.
Explore the source record for details and available documents.
Scarring or undercorrection occurs in a small percentage of patients after myopic photorefractive keratectomy. Scarring occurred in 1.8% of 298 patients with a baseline myopia of 6.0 diopters or less, increasing to 8.8% in those with corrections of more than 6.0 D. Undercorrection of more than 1 D occurred in 2.7% of the eyes with a baseline myopia of up to -6.0 D. A much greater incidence of undercorrection (30% to 40%) was found after corrections of more than 6.0 D. Thirty eyes in 30 patients were reoperated because of scarring (11 eyes) and/or undercorrection (27 eyes) and were observed for 6 to 18 months (average, 7.8 months). Only one of the eyes has shown mild scar formation after this second laser treatment. Sixty-three percent of these patients had a manifest refraction between -1.0 D and +1.0 D six months after reoperation. Repeated phototablation seems to be a valuable technique for treatment of undercorrection and/or scarring after photorefractive keratectomy.
Moricizine has been touted as having a low incidence of proarrhythmic effects. We present a case of proarrhythmia from moricizine, which presented as exercise induced ventricular tachycardia, and review the literature suggesting that this antiarrhythmic drug shares the proarrhythmic profile of other agents with predominant type Ic action. We conclude that moricizine has certain clinical and electrophysiological features that resemble type Ic antiarrhythmic agents. Precautions similar to those used when prescribing other drugs of this type should be followed when prescribing moricizine, including predischarge exercise testing.
Explore the source record for details and available documents.
Erythropoietin (Ep) regulates the proliferation and differentiation of erythroid progenitor cells, but whether it functions solely as a survival factor or also acts as a mitogen is unresolved. Because late erythroid progenitor cells (CFU-E) are largely in cell cycle, we examined this issue by using an Ep-dependent, murine erythroleukemia cell line, HCD-57. In the presence of human Ep and fetal calf serum, HCD-57 cells had a doubling time of approximately 24 hours, and during log-phase growth approximately 36% of the cells were in G1, 45% in S, and 19% in G2/M. With Ep deprivation, there was a gradual loss of viability and an arrest of proliferation with a 44% increase in the G0/G1 population, which could be reversed by reexposure to Ep even after 72 hours of hormone withdrawal. As little as 2 hours of exposure to Ep was sufficient to stimulate DNA synthesis, and the lag time for initiation of DNA synthesis after exposure to the hormone was approximately 10 hours as measured by either incorporation of labeled thymidine into DNA or cell cycle analysis by flow cytometry. RNA synthesis, by contrast, was initiated within 2 hours after exposure to Ep and did not require DNA synthesis. Total cell DNA content increased after exposure to Ep, indicating that it was acting as mitogen in HCD-57 cells. Ep was also able to stimulate DNA synthesis in the absence of serum as well as in its presence, indicating that the hormone could act as both a competence and a progression factor. Qualitative analysis of the integrity of HCD-57 DNA by electrophoresis in agar as well as direct measurement of DNA fragmentation after metabolic labeling with radioactive thymidine indicated that programmed cell death was occurring that could be reduced but not completely prevented by Ep. These data indicate that Ep acts as both a mitogen and a survival factor for HCD-57 cells.
Within human insulin receptor gene there are three consensus binding sites for the CAAT/enhancer binding protein (C/EBP). Two sites are located in the 5' flanking region and the other is in the first intron. We have studied the ability of these sequences to be regulated by C/EBP. A eukaryotic expression vector containing these sequences can be transactivated in a dose-dependent manner by a C/EBP expression vector when co-transfected into NIH-3T3 cells. In addition, double stranded oligonucleotides corresponding to two of these sequences can bind C/EBP in a gel retardation assay. These two oligonucleotides can complete with each other to bind C/EBP. These findings suggest that this transcription factor may play a role in the regulation of insulin receptor gene expression in vivo.