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Biomedical subjects

L Fowler

Publications and source records attributed to L Fowler.

11 recordsLinked to original sources

35H, a sequence isolated as a protein kinase C binding protein, is a novel member of the adducin family.

We recently cloned a partial cDNA (35H) for a protein kinase C (PKC) binding protein from a rat kidney cDNA library and demonstrated that it is a PKC substrate in vitro (Chapline, C., Ramsay, K., Klauck, T., and Jaken, S. (1993) J. Biol. Chem. 268, 6858-6861). Additional library screening and 5' rapid amplification of cDNA ends were used to obtain the complete open reading frame. Amino acid sequence analysis, DNA sequence analysis, and Northern analysis indicate that 35H is a unique cDNA related to alpha-and beta-adducins. Antisera prepared to the 35H bacterial fusion protein recognized two polypeptides of 80 and 90 kDa on immunoblots of kidney homogenates and cultured renal proximal tubule epithelial cell extracts. The 35H-related proteins were similar to alpha- and beta-adducins in that they were preferentially recovered in the Triton X-100-insoluble (cytoskeletal, CSK) fraction of cell extracts and were predominantly localized to cell borders. Phorbol esters stimulated phosphorylation of CSK 35H proteins, thus emphasizing that sequences isolated according to PKC binding activity in vitro are also PKC substrates in vivo. The phosphorylated forms of the 35H proteins were preferentially recovered in the soluble fraction, thus demonstrating that phosphorylation regulates their CSK association and, thereby, their function in regulating cytoskeletal assemblies. We have isolated another PKC binding protein partial cDNA (clone 45) from a rat fibroblast library with substantial homology to alpha-adducin. Antisera raised against this expressed sequence recognized a protein of 120 kDa, the reported size of alpha-adducin, on immunoblots of renal proximal tubule epithelial cell extracts. A 120-kDa protein that cross-reacts with the clone 45 (alpha-adducin) antisera coprecipitated with 35H immunecomplexes, indicating that alpha-adducin associates with 35H proteins in vivo. Taken together, these results indicate that 35H is a new, widely expressed form of adducin capable of forming heterodimers with alpha-adducin. We propose naming this adducin homologue gamma-adducin.

Amino Acid Sequence

Family psychoeducation: chronic psychiatrically ill Caribbean patients.

This article described a method of patient and family intervention designed for psychotic patients who are prone to relapse. Issues addressed in a monthly group meeting were designed to clarify, inform, and support families on the facts of schizophrenia and bipolar disorder. This format succeeded in improving the rate of recidivism in the population of Caribbean patients because it clarified distortions of the nature of the illnesses and made obvious that medication compliance was separate and did not intrude on the culture and belief systems. Family dynamics were not a focus in this psychoeducation program, but alliances, boundaries, and process did change over the course of the 6 months of the program. Family members were engaged relatively easily and responded when it was clear there was no intention to intrude on culture or personal beliefs. Many expressed anger and frustrations that such a program had not been offered before, especially those families whose relatives had experienced multiple readmissions. The questionnaires clearly illustrated an increase in knowledge and understanding about the illness, and this correlated with reduced recidivism. A major effort is made to maintain contact with patients and their families following discharge from the day hospital for up to 3 years to ensure their follow-through. Follow-up phone calls ensure 100% follow-up. For the past few years, we have found that ongoing contact is also useful on a reduced frequency to reinforce the concepts communicated initially.

Adolescent

Surgical management of perilymphatic fistulas: a Portland experience.

A comprehensive review of our series of surgical perilymphatic fistula (PLF) repairs, as well as a review of published results from other otologists, suggested an unacceptably high rate of postoperative PLF recurrence. Some recurrences were related to specific events (i.e., coughing, strenuous activity, Valsalva-type maneuvers). However many cases had no apparent cause. Rather, the patients' symptoms recurred spontaneously, and at reoperation the graft was seen to have not "taken," suggesting graft failure rather than "patient failure." After a critical evaluation of current PLF surgical procedures and state-of-the-art concepts of wound healing, we developed a new surgical technique for PLF closure. Combining the use of laser graft-site preparation, an autologous fibrin glue "buttress," and a program of postoperative activity restriction, the new procedure allowed us to achieve statistically significant improvements in graft retention and surgical outcome, with recurrences dropping from 27 percent to 8 percent. In addition, complete resolution or significant symptomatic improvement occurred in 89 percent of patients with vertigo and/or dizziness and in 84 percent with disequilibrium. We conclude that this new surgical technique is an important addition to the otologic surgeon's arsenal for PLF management.

Adolescent

Surgical management of perilymph fistulas. A new technique.

A wide range of recurrence rates (21% to 47%) for perilymph fistula repairs have been reported in the otology literature. An improved surgical technique developed at the Portland (Ore) Good Samaritan Hospital and Medical Center Neurotology Department was used to repair perilymph fistulas in 58 patients from October 1986 to October 1988. Our recurrence rate was reduced from 27% in a 1982-1985 study to 8% in our study. At 1 year postoperatively, improvements in disequillibrium, dizziness, and vertigo were comparable with results of older surgical techniques. Functional outcomes were also good: 83% of patients returned to normal activities of daily living, and 71% also returned to school or resumed gainful employment outside the home.

Adolescent

Human immunoglobulin therapy for preeclampsia associated with lupus anticoagulant and anticardiolipin antibody.

A patient with lupus anticoagulant and anticardiolipin antibody developed preeclampsia at 24 weeks' gestation. Therapy with human immunoglobulin (Ig) resulted in stabilization of preeclampsia and suppression of the lupus anticoagulant. Anticardiolipin antibody titers were partially suppressed. Preeclampsia worsened at 32 weeks' gestation, and a healthy infant was delivered. For patients with preeclampsia secondary to lupus anticoagulant before the fetus is viable, human Ig is a potential therapeutic option.

Adult

Ceftriaxone versus povidone iodine in preventing wound infections following biliary surgery.

The effect of either prophylactic antibiotic or wound antiseptic on bile bacteriology, wound and other postoperative sepsis has been studied in a controlled prospective randomised trial of 243 patients undergoing biliary surgery at a district general hospital. Wound infection rates were significantly less in patients given intravenous ceftriaxone (1%) at induction of anaesthesia when compared to povidone iodine sprayed into the wound at the completion of surgery (9%) (P = 0.02). In all but one patient infected wounds grew organisms identical to those cultured from the bile. There were also fewer chest and urinary infections in the ceftriaxone group but this was not statistically significant.

Administration, Topical

Cultured fetal rat myoblasts release peptide growth factors which are immunologically and biologically similar to somatomedin.

The production of immunologically and biologically active somatomedin activity from isolated myoblasts and fibroblasts from fetal rats of 21 days gestational age was investigated. Myoblast-rich cell populations were derived from primary cultures of dispersed muscle cells by the tendency of myoblasts to become detached from the culture dish in the presence of cytochalasin B. Fibroblasts were obtained from fetal muscle. Culture medium conditioned by exposure to myoblasts for 48 hours produced an increased incorporation of both [35S]sulphate and [3H]thymidine by explants of fetal rat costal cartilage in vitro compared to fresh medium. Myoblast-conditioned medium also contained somatomedin-C-like immunoreactivity which diluted in parallel with partially purified human somatomedin-C (3,271 +/- 446 mU/mg cell protein; mean +/- SEM, seven experiments). Medium conditioned by exposure to fetal rat fibroblasts did not promote isotope uptake by fetal rat cartilage above control values, and contained only low levels of somatomedin-C-like immunoreactivity (343 +/- 89 mU/mg cell protein, three experiments). The release of both somatomedin bioactivity and immunoreactivity into conditioned medium was significantly reduced by the incubation of myoblasts in the presence of rat growth hormone (100 ng/ml and 500 ng/ml). We conclude that fetal rat myoblasts released growth factor activity during culture which exhibited biological and immunologic characteristics of somatomedin. Since the bioactivity was demonstrated on skeletal tissues from rat fetuses of the same gestational age as those that yielded myoblasts such growth factor release may be physiological.

Animals

Effect of allergic bronchoconstriction on airways epithelial permeability to large polar solutes in the guinea pig.

The effect of allergic bronchoconstriction on the permeability of the airway mucosa to large hydrophilic polar solutes was investigated in the guinea pig. After specific antigen (ovalbumin) challenge, there was a significant increase in the plasma levels of horseradish peroxidase (HRP) (molecular weight, approximately 40,000 daltons), 3H-dextran (approximately 10,000 daltons), and 14C-mannitol (approximately 182 daltons) compared with that in control animals aerosol-challenged with a nonspecific protein, lactoglobulin. The morphologic correlates of this enhanced transepithelial permeability after ovalbumin challenge appeared to be (1) increased HRP penetration of the epithelial tight junctions (p less than 0.001), and (2) increased mucus discharge from surface lining goblet cells. We conclude that antigen-induced bronchoconstriction leads to an increase in tracheobronchial permeability to macromolecules, and this effect is likely to be mediated by an increased paracellular as well as transcellular vesicular movement of large polar solutes across the airway epithelial barrier.

Animals

Tissue distribution of primaquine in the rat.

The distribution of primaquine was measured in seven rat tissues at 15-180 min after the intraperitoneal injection of the antimalarial 8-aminoquinoline. The half-life of unmetabolized primaquine was 4.0 h in lung, 1.7-1.9 h in blood, spleen, kidney and heart, and 1.2 h in liver. At each interval, the concentrations of unmetabolized primaquine were (in order): lung greater than liver, kidney, spleen greater than heart greater than brain greater than or equal to blood. At 3 h after the injection of [6-O-methyl-3H]primaquine, unmetabolized primaquine constituted 10% of the total 3H in blood and 40-60% of the total 3H in liver, brain, heart and kidney.

Animals