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Biomedical subjects

R M Freeman

Publications and source records attributed to R M Freeman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Is antenatal bladder neck mobility a risk factor for postpartum stress incontinence?

OBJECTIVE: To assess the contribution of constitutional factors, as demonstrated by antenatal bladder neck mobility, in the development of postpartum urinary stress incontinence. DESIGN: A prospective investigational study. SETTING: General district hospital. POPULATION: One hundred and three primigravid women with no pre-existing urinary incontinence or neurological disorder. METHODS: Antenatal and postnatal measurement of bladder neck mobility using perineal ultrasound. MAIN OUTCOME MEASURE: Urinary stress incontinence at 10-14 weeks postpartum. RESULTS: Women with postpartum urinary stress incontinence have significantly greater antenatal bladder neck mobility than those women continent postpartum. There were no significant differences in any labour or delivery variables, including mode of delivery, between the postpartum continent and incontinent women. CONCLUSIONS: There is evidence for a constitutional risk factor (eg, defective pelvic floor connective tissue in the development of postpartum stress incontinence).

Adult↗
PubMed1996

Multiple requirements for SHPTP2 in epidermal growth factor-mediated cell cycle progression.

Using transient overexpression and microinjection approaches, we examined SHPTP2's function in growth factor signaling. Overexpression of catalytically inactive SHPTP2 (PTP2CS) but not catalytically inactive SHPTP1, inhibited mitogen-activated protein (MAP) kinase activation and Elk-1 transactivation following epidermal growth factor (EGF) stimulation of 293 cells. An SHPTP2 mutant with both C-terminal tyrosyl phosphorylation sites converted to phenylalanine (PTP2YF) was also without effect; moreover, PTP2YF rescued PTP2CS-induced inhibition of EGF-induced Elk-1 transactivation. PTP2CS did not inhibit transactivation by activated Ras, suggesting that SHPTP2 acts upstream of or parallel to Ras. Neither PTP2CS nor PTP2YF inhibited platelet-derived growth factor (PDGF)-induced Elk-1 transactivation. Thus, protein-tyrosine phosphatase activity, but not tyrosyl phosphorylation of SHPTP2, is required for the immediate-early responses to EGF but not to PDGF. To determine whether SHPTP2 is required later in the cell cycle, we assessed S-phase entry in NIH 3T3 cells microinjected with anti-SHPTP2 antibodies or with a glutathione S-transferase (GST) fusion protein encoding both SH2 domains (GST-SH2). Microinjection of anti-SHPTP2 antibodies prior to stimulation inhibited EGF- but no PDGF- or serum-induced S-phase entry. Anti-SHPTP2 antibodies or GST-SH2 fusion protein could inhibit EGF-induced S-phase entry for up to 8 h after EGF addition. Although MAP kinase activation was detected shortly after EGF stimulation, no MAP kinase activation was detected around the restriction point. Therefore, SHPTP2 is absolutely required for immediate-early and late events induced by some, but not all, growth factors, and the immediate-early and late signal transduction pathways regulated by SHPTP2 are distinguishable.

Animals↗
PubMed1995

The SH2-containing protein-tyrosine phosphatase SH-PTP2 is required upstream of MAP kinase for early Xenopus development.

SH-PTP2, the vertebrate homolog of Drosophila corkscrew, associates with several activated growth factor receptors, but its biological function is unknown. We assayed the effects of injection of wild-type and mutant SH-PTP2 RNAs on Xenopus embryogenesis. An internal phosphatase domain deletion (delta P) acts as a dominant negative mutant, causing severe posterior truncations. This phenotype is rescued by SH-PTP2, but not by the closely related SH-PTP1. In ectodermal explants, delta P blocks fibroblast growth factor (FGF)- and activin-mediated induction of mesoderm and FGF-induced mitogen-activated protein (MAP) kinase activation. Our results indicate that SH-PTP2 is required for early vertebrate development, acting as a positive component in FGF signaling downstream of the FGF receptor and upstream of MAP kinase.

Activins↗
PubMed1993

Tyrosyl phosphorylation and growth factor receptor association of the human corkscrew homologue, SH-PTP2.

The pivotal role of tyrosine kinases in signal transduction is well established, but the role of tyrosine phosphatases remains obscure. The discovery of src homology 2 domain-containing protein tyrosine phosphatases suggested roles for these molecules in growth factor signaling pathways, since src homology 2 domains direct association of downstream signaling molecules with activated growth factor receptors and other phosphotyrosyl proteins. We have found that SH-PTP2, a putative homologue of Drosophila corkscrew, associates in vivo with the ligand-activated epidermal growth factor and platelet-derived growth factor receptors. The N-terminal src homology 2 domain of SH-PTP2 directly associates with activated receptors. SH-PTP2 itself is a phosphoprotein, and it becomes tyrosyl phosphorylated upon growth factor activation. These findings suggest several possible models for SH-PTP2 signaling.

3T3 Cells↗
PubMed1992

Identification of a human src homology 2-containing protein-tyrosine-phosphatase: a putative homolog of Drosophila corkscrew.

src homology 2 (SH2) domains direct binding to specific phosphotyrosyl proteins. Recently, SH2-containing protein-tyrosine-phosphatases (PTPs) were identified. Using degenerate oligonucleotides and the PCR, we have cloned a cDNA for an additional PTP, SH-PTP2, which contains two SH2 domains and is expressed ubiquitously. When expressed in Escherichia coli, SH-PTP2 displays tyrosine-specific phosphatase activity. Strong sequence similarity between SH-PTP2 and the Drosophila gene corkscrew (csw) and their similar patterns of expression suggest that SH-PTP2 is the human corkscrew homolog. Sequence comparisons between SH-PTP2, SH-PTP1, corkscrew, and other SH2-containing proteins suggest the existence of a subfamily of SH2 domains found specifically in PTPs, whereas comparison of the PTP domains of the SH2-containing PTPs with other tyrosine phosphatases suggests the existence of a subfamily of PTPs containing SH2 domains. Since corkscrew, a member of the terminal class signal transduction pathway, acts in concert with D-raf to positively transduce the signal generated by the receptor tyrosine kinase torso, these findings suggest several mechanisms by which SH-PTP2 may participate in mammalian signal transduction.

Amino Acid Sequence↗
PubMed1988

Subarachnoid anaesthesia for elective caesarean section. A comparison of two hyperbaric solutions.

Forty patients who underwent elective lower segment Caesarean section under subarachnoid anaesthesia received either 2.0 ml 0.5% cinchocaine in 6% dextrose or 2.5 ml 0.5% bupivacaine in 8% dextrose via a 26-gauge needle with the patient in the left lateral position. Onset time was rapid in both groups and the distribution of maximum ascent of sensory analgesia was T1-T6. Efficacy of analgesia was greater in the bupivacaine group, although the duration of both sensory and motor blockade was shorter than following cinchocaine. There were no significant differences between the two groups either in the incidence and severity of complications or in the condition of the neonates. The high incidence (50-65%) and often profound extent of hypotension seen throughout the trial, confirm the ineffectiveness of crystalloid preload of 1500 ml as a single prophylaxis against hypotension.

Adult↗
PubMed1987

Response surface of daily thyroid hormone rhythms in young chickens exposed to constant ambient temperature.

Response surface models were developed by multiple regression techniques to describe daily rhythms of plasma thyroid hormones in young chickens during acclimation to a wide range of ambient temperatures (Ta). Seventy-two Leghorn cockerels were raised in six environmental chambers under a 12L:12D light/dark cycle. Beginning at 21 days of age, two replicate chambers provided Ta treatments of 10, 24, or 38 degrees. During Day 6 of acclimation, blood samples were obtained at 0800, 1200, 1600, 2000, 2400, and 0400 hr for thyroid hormone analyses. Plasma triiodothyronine (T3) levels showed a convex response to the experimental region (10 to 38 degrees, and 0800 to 0400 hr under a 12L:12D light/dark cycle), whereas the plasma thyroxine (T4) response surface was concave. In particular, heat exposure (38 degrees) depressed (P less than .01) plasma T3 levels (2.8 ng/ml) below those of birds held at 24 degrees (4.5 ng/ml), whereas elevated (p less than 0.05) T3 concentrations were found in the 10 degrees treatment (5.0 ng/ml). Plasma T3 levels rose gradually during photophase and slowly declined during scotophase. Plasma T4 concentrations followed an opposite pattern with the daily zenith in scotophase and the nadir during photophase. Plasma T4 levels were sharply elevated in birds maintained at 38 degrees, particularly during scotophase. Although Ta did not change the daily amplitude or circadian frequency of the plasma T3 rhythm, an increased frequency or ultradian rhythm of plasma T4 was observed in cold-acclimated birds. The counter-responses of T3 and T4 to heat exposure and phase of the light/dark cycle were best seen in the molar ratio of plasma T3/T4 levels. The average daily T3/T4 molar ratio for heat-exposed birds was 0.16 while the average T3/T4 ratio was higher (P less than 0.01) for the 10 degrees (0.46) and 24 degrees (0.41) treatments. The opposing responses of plasma T3 and T4 levels to a wide range of Ta and phase of the light/dark cycle support a major role for circulating T3 in metabolic adjustments that chickens make to changes in the photothermal environment.

Animals↗
PubMed1987

Reducing the hemorrhagic complications of hemodialysis: a controlled comparison of low-dose heparin and citrate anticoagulation.

We report a randomized prospective study comparing the results of anticoagulation using hypertonic trisodium citrate and low-dose controlled heparin during 45 hemodialysis treatments performed on patients determined to be at high or very high risk for bleeding. Dialysis-associated bleeding was more frequent following low-dose controlled heparin anticoagulation than during hypertonic citrate therapy (P less than .05). Dialysis effectiveness measured by postdialysis chemistries and weight loss was equivalent in the two groups.

Anticoagulants↗
PubMed1987

Blunted peripheral tissue responsiveness to thyroid hormone in uremic patients.

To understand the biologic significance of the low triiodothyronine (T3) syndrome in patients with chronic renal failure (CRF), we examined thyroid hormone profile, basal O2 uptake (VO2), and peripheral blood mononuclear leukocyte (PBL) ouabain binding in these patients and in the control subjects before and after L-triiodothyronine (T3) and sodium ipodate treatment. In the controls (N = 8), T3 administration increased serum total T3 from 136 +/- 15 to 232 +/- 11 ng/dl, and reduced total thyroxine (T4) from 8.14 +/- 0.56 to 6.08 +/- 0.43 micrograms/dl, free T4 from 1.59 +/- 0.12 to 1.03 +/- 0.05 ng/dl and thyroid-stimulating hormone (TSH) from 1.74 +/- 0.24 to 0.41 +/- 0.09 microU/ml. VO2 increased from 2.66 +/- 0.11 to 3.15 +/- 0.09 ml/kg/min. Ipodate treatment, on the other hand, resulted in a reduction of serum total T3 to 102 +/- 21 ng/dl, an increase in total T4 to 9.59 +/- 0.50 micrograms/dl, free T4 to 1.91 +/- 0.13 ng/dl and TSH to 3.64 +/- 1.14 microU/ml. VO2 decreased to 2.43 +/- 0.06 ml/kg/min. P values ranged from less than 0.05 to less than 0.001. In the CRF patients (N = 14), T3 treatment also resulted in a rise in serum total T3 from 75 +/- 5 to 185 +/- 8 ng/dl. Total T4 declined from 6.68 +/- 0.34 to 5.18 +/- 0.48 micrograms/dl, free T4 from 0.85 +/- 0.1 to 0.67 +/- 0.08 ng/dl and TSH from 3.67 +/- 0.86 to 0.94 +/- 0.3 microU/ml. VO2, however, did not change (from 2.91 +/- 0.12 to 2.99 +/- 0.17 ml/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Regional anticoagulation: hemodialysis with hypertonic trisodium citrate.

We have developed a simplified method for performing regional citrate anticoagulation during hemodialysis. High ultrafiltration rates and specialized equipment were obviated by the use of a 1.6-mol/L trisodium citrate solution and a standard calcium-containing dialysate. Thirty-six dialyses were performed with this technique on 14 stable and 22 high bleeding risk patients. There was no significant decline in plasma-ionized calcium during citrate dialysis, ie, 3.85 +/- 0.34 mg/dL (mean +/- SE) predialysis, to 3.31 +/- 0.26 postdialysis; furthermore, no patient developed neuromuscular symptoms or evidence of cardiovascular instability from hypocalcemia. Serum sodium rose with this procedure, but not to hypernatremic levels. This method of citrate dialysis is safe and effective during continuous blood flow (double-needle) hemodialysis, and is no more difficult to perform than conventional heparin dialysis. Single-needle (reciprocating blood flow) hemodialysis was successfully performed by the additional use of a calcium-free dialysate and separate calcium chloride infusion (10% calcium chloride), but risks the production of unexpected hypercalcemia.

Bicarbonates↗
PubMed1986

Basal oxygen uptake: a new technique for an old test.

To assess the metabolic effects of T4 and T3, we measured serum total T4 (TT4), free T4 (FT4), total T3 (TT3), TSH, and basal oxygen uptake (VO2) in eight normal subjects in the basal state and after treatment with L-T3 (T3) and sodium ipodate for 2 weeks. T3 treatment resulted in a rise of serum TT3 from a baseline of 137 +/- 16 (+/- SE) to a peak of 239 +/- 15 ng/dl. Serum TT4 declined from 8.14 +/- 0.56 to 6.08 +/- 0.43 micrograms/dl, FT4 from 1.59 +/- 0.13 to 1.03 +/- 0.05 ng/dl, and TSH from 1.74 +/- 0.24 to 0.56 +/- 0.16 microU/ml. Basal VO2 increased from 2.66 +/- 0.11 to 3.15 +/- 0.09 ml/kg X min. Ipodate, on the other hand, led to a lower serum TT3 concentration (102 +/- 21 ng/dl), higher serum TT4 and FT4 (9.59 +/- 0.5 micrograms/dl and 1.91 +/- 0.13 ng/dl, respectively), and elevated TSH (3.64 +/- 0.14 microU/ml). Basal VO2 was reduced to 2.44 +/- 0.06 ml/kg X min. Linear regression analysis revealed an excellent positive correlation between serum TT3 and basal VO2 (n = 25; r = 0.747; P less than 0.001) and a significant negative correlation between serum TT3 and TSH (n = 26; r = -0.526; P less than 0.01). Serum TT4 and FT4 correlated negatively with VO2 and positively with serum TSH. The higher T4 level during ipodate treatment was associated with lower VO2 and higher TSH, and vice versa when T4 was suppressed while receiving T3. When ipodate was given concomitantly with T3 to five subjects, only the effects of T3, characterized by increased VO2 and decreased TSH, were evident. These data indicate that both basal VO2 and serum TSH are sensitive indices of thyroid hormone activities. The latter gives only the directional change (hyper- or hypothyroidism), while the former more accurately quantitates the magnitude of the derangement. Moreover, it appears that in man, T3, and not T4, is the primary hormone that regulates thermogenesis and TSH secretion.

Adult↗
PubMed1985

Cellular response to peritonitis among peritoneal dialysis patients.

White blood cell counts and differential cell counts were performed on 249 peritoneal dialysis effluents from 48 patients using chronic peritoneal dialysis. The finding of more than 50% polymorphonuclear leukocytes in the dialysate was a more sensitive indicator of peritonitis than was an absolute cell count of 100 cells/microL. This finding was true for patients using intermittent peritoneal dialysis, continuous ambulatory peritoneal dialysis, and continuous cycling peritoneal dialysis.

Ascitic Fluid↗
PubMed1985

Protective adaptation of low serum triiodothyronine in patients with chronic renal failure.

Low serum triiodothyronine (T3) concentration is frequently found in patients with chronic renal failure (CRF). To test the hypothesis that this may serve to minimize protein catabolism in these patients, we measured nitrogen balance (Nb) in seven CRF and four control subjects in the basal state and when serum T3 concentration was elevated by L-triiodothyronine (LT3) and suppressed by sodium ipodate administration. In the basal state, both the controls and the CRF patients were in positive Nb, 0.02 +/- 0.51 and 0.58 +/- 0.34 g/day, respectively. During LT3 administration, Nb decreased to -0.80 +/- 0.39 g/day in the CRF patients (P less than 0.01), but remained positive, 0.22 +/- 0.67 g/day, in the controls. There was a significant negative correlation between serum T3 concentration and Nb in the CRF patients (r = -0.63, P less than 0.005), but not in the controls. Furthermore, urea nitrogen generation rate, calculated from urea kinetics, increased from a baseline of 4.6 +/- 0.55 to 6.0 +/- 0.50 mg/min during LT3 administration in the CRF patients (P less than 0.01). Sodium ipodate, which significantly lowered serum T3 concentrations, had little effect on nitrogen metabolism in the controls and the CRF patients. These data support the concept that low serum T3 concentrations may confer a protective effect on CRF patients regarding protein-nitrogen conservation and provide a rationale for not correcting such deficiency.

Adaptation, Physiological↗
PubMed1985

Psychological features of women with idiopathic detrusor instability.

Psychological tests were completed by 57 incontinent women with idiopathic detrusor instability, and compared with those of 22 women with genuine stress incontinence (an anatomical disorder) and published norms. The previously reported findings of hysterical personality traits, situational stresses and sexual dysfunction in patients with detrusor instability were not confirmed. Higher scores for anxiety, neuroticism, hostility, and depression were found in patients with detrusor instability than in controls. These findings, known associations of psychosomatic disorders, lend further support to the view that idiopathic detrusor instability is a psychosomatic disorder.

Adult↗