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Biomedical subjects

P Parker

Publications and source records attributed to P Parker.

At least 19 recordsLinked to original sources

Excimer laser photorefractive keratectomy in high myopia. A multicenter study.

Excimer photorefractive keratectomy was performed at three centers on 16 highly myopic eyes (8 diopters [D] or more) and followed up for 6 months. Ablation depths ranged from 137 to 230 microns. The preoperative spherical equivalent of myopia ranged from -8.62 D to -14.50 D (mean +/- SD, -11.57 +/- 1.62 D). Six months after surgery, the mean refraction (spherical equivalent) was -0.90 +/- 2.13 D. Eleven of 16 eyes achieved refractions within 2 D of that attempted. All eight patients at one site were treated with a maximum-beam diameter of 6.0 mm and were corrected to within 2 D of that attempted, and all were 20/40 or better uncorrected. Three of eight eyes at the other two sites were treated with a 5.5- or 5.6-mm maximum-beam diameter, which achieved corrections within 2 D of that attempted. The epithelium healed within 3 to 4 days, and there were no erosions. Mild subepithelial reticular haze, similar to that seen with excimer photorefractive keratectomy for lower myopia, was seen in all patients, with two patients experiencing more significant corneal haze. This peaked at 3 to 6 weeks and then gradually diminished. All but two patients had a return of their best corrected preoperative visual acuity to within one Snellen line at 6 months. This preliminary study shows excimer photorefractive keratectomy to be a promising surgical treatment for patients with higher myopia.

Adult

The effects of estradiol on pituitary responsiveness to dopamine in vitro: a comparison of ovariectomized Fischer 344 and Holtzman rats.

The objective of this study was to determine if the effectiveness of dopamine as an inhibitor of prolactin is altered by estradiol in strains of rats which show marked differences in estrogen-induced pituitary hyperplasia. Groups of Fischer 344 and Holtzman Sprague-Dawley rats were ovariectomized and implanted with Silastic capsules of estradiol. Rats were sacrificed by rapid decapitation following a brief period of ether anesthesia at 2, 4, 6, 8 weeks (F-344) or at 2 and 8 weeks (Holtzman) of estradiol treatment. The pituitary was removed and cut into fragments which were either snap frozen for initial prolactin content measurements or incubated for 60 min in the presence or absence of dopamine (1 x 10(-6) M). Prolactin was measured in the plasma, in sonicates of the pituitary and in the incubation medium by double antibody radioimmunoassay. Pituitary weight and plasma levels of prolactin were significantly less in Holtzman rats compared to Fischer 344 females at 2 or 8 weeks of estradiol treatment but pituitary concentrations of prolactin were not different between the two strains. Pituitary fragments from Fischer 344 rats studied at 2 and 4 weeks of estradiol treatment did not respond to the removal of dopamine in vitro whereas pituitary fragments from Holtzman rats obtained at 2 weeks of estradiol treatment did release significantly more prolactin in the absence than in the presence of dopamine. Pituitary fragments taken from Fischer 344 rats at 6 and 8 weeks were responsive to dopamine whereas pituitary tissue from Holtzman rats was not responsive at 8 weeks. The data indicate that temporal differences in responsiveness to the inhibitory effects of dopamine occur in strains which are susceptible or resistant to the formation of pituitary tumors following prolonged estradiol treatment.

Analysis of Variance

Occupational injuries among minors doing farm work in Washington State: 1986 to 1989.

BACKGROUND: There is growing evidence that many children are injured while engaged in agricultural work. However, little specific information on farm work-related injuries among minors is available, probably because employment or workers' compensation data for children are hard to obtain. METHODS: Workers' compensation data were used to evaluate occupational injuries among children in Washington State from 1986 through 1989. The frequency and severity of injuries among minors doing farm work were compared with the distributions of injuries among minors working in food service and all other occupations by year of injury, age of injury, and month and hour of injury. RESULTS: A total of 16,481 claims filed by children under age 18 were evaluated. Although farm workers accounted for only 7% of all claims, they made up 36% of claims filed by children under age 14, and 17% of claims filed by children aged 14 or 15. Injuries classified as serious accounted for 26% of farm worker claims compared with only 16% of all claims filed by children. CONCLUSIONS: Although injury rates could not be developed owing to the lack of denominator data, this study demonstrates that farm work is dangerous for young children.

Accidents, Occupational

Clinical use of the 193-nm excimer laser in the treatment of corneal scars.

Phototherapeutic keratectomy using a 193-nm excimer laser was performed at four centers on 33 sighted patients with corneal opacity and/or irregular astigmatism. Pathologic conditions included anterior stromal and superficial scarring from postinfectious and posttraumatic causes, including inactive herpes simplex virus, anterior corneal dystrophies, recurrent erosions, granular dystrophy, and band keratopathy. Most patients received peribulbar anesthesia and underwent removal of the epithelium prior to laser ablation. A majority of patients had a reduction in the amount of corneal scarring and approximately half had improved visual acuity. No intraocular reaction or changes in endothelial counts were seen, and some patients avoided the need for penetrating keratoplasty. Reepithelialization usually occurred within 4 or 5 days and we noted no significant scarring secondary to use of the laser. It was difficult to eliminate preexisting irregular astigmatism despite the use of surface modulators, such as methylcellulose. A hyperopic shift secondary to corneal flattening was encountered in approximately 50% of the patients. A combination of myopic ablation, followed immediately by a secondary hyperopic steepening, may minimize this refractive change. The 193-nm excimer laser is an effective new tool in the treatment of selected patients with superficial corneal opacity from a variety of conditions.

Adult

The use of the 193-nm excimer laser for myopic photorefractive keratectomy in sighted eyes. A multicenter study.

Photorefractive keratectomy was performed at three centers using the 193-nm excimer laser on 31 sighted myopic eyes. Preoperative refractive errors (spherical equivalent) ranged from -12.00 to -4.00 diopters (D) (mean, -6.49 +/- 1.75 D). Peribulbar anesthesia, a 5.2- to 6.0-mm beam diameter, and topical corticosteroids were used for up to 6 months after surgery. The epithelium healed within 3 to 4 days, and all patients returned to their best corrected visual acuity within 1 line of their preoperative acuity. There was minimal subepithelial reticular haze, peaking at 3 weeks and diminishing over the next 3 to 4 months, which was not felt to be visually significant. At 6 months, the average residual refractive error was -1.85 +/- 2.5 D. Sixty-eight percent of eyes were corrected within 2 D and 55% within 1 D of attempted correction. There was no significant change in astigmatism, contrast sensitivity, corneal sensation, or endothelial cell counts. This preliminary work shows that photorefractive keratectomy has promise in the reduction of moderate myopia.

Adult

Importance of bone marrow cytogenetic evaluation before autologous bone marrow transplantation for Hodgkin's disease.

Alkylating agents used either with or without radiation therapy have been associated with the development of myelodysplastic syndrome (MDS) and acute nonlymphoblastic leukemia (ANLL) after treatment of both malignant and nonmalignant disorders. This report describes seven patients with recurrent Hodgkin's disease (HD) evaluated for bone marrow transplantation (BMT) who developed chromosomal abnormalities, and emphasizes the importance of bone marrow cytogenetic studies before bone marrow harvest. Three patients with histologically normal bone marrow underwent autologous BMT and subsequently developed an MDS or ANLL. Four patients had the clonal abnormality detected before bone marrow harvest and did not proceed to BMT.

Adult

Effector-dependent conformational changes in protein kinase C gamma through epitope mapping with inhibitory monoclonal antibodies.

Three monoclonal antibodies (mAb) directed against the regulatory domain of the protein kinase C gamma (PKC gamma); 15G4, 5A2 and 36G9, were shown to display distinct properties with respect to PKC gamma kinase activity [Cazaubon, S., Marais, R., Parker, P. & Strosberg, A.D. (1989) Eur. J. Biochem. 182, 401-406]. The mAb 5A2 and 36G9, which act as potent inhibitors of the cofactor-dependent kinase activity, can no longer bind PKC gamma in the presence of phosphatidylserine and phosphatidylserine/phorbol ester, respectively; 15G4 binding is not influenced by effectors. Due to this functional relationship between the inhibitory mAb- and cofactor-binding sites, we sought to localize the mAb epitopes with respect to the functional sites of PKC gamma. For this purpose, several deletions were introduced at the 5' end of the PKC gamma cDNA and the mutant proteins were expressed in Escherichia coli. The determination of the immunoreactivity of the deleted PKC gamma proteins shows that the amino acid residues essential to the binding of 5A2 and 36G9 are directly adjacent to the second cysteine-rich motif: these are contained in the sequences at positions 151-163 and 164-197, respectively. In addition, various deletions around the C1 region of the regulatory domain allowed the identification of the second cysteine-rich motif as a functional binding site for phorbol dibutyrate. These deletion studies thus demonstrate that the epitopes recognized by the inhibitory mAbs 5A2 and 36G9 are distinct from the cofactor-binding sites. This suggests that the binding of phosphatidylserine and phorbol ester induce conformational changes in the regulatory domain of PKC, which are thus responsible for the loss of the 5A2 and 36G9 immunoreactivity of the native protein. In this conformational state, PKC gamma conserves its ability to interact with the non-inhibitory mAb 15G4. By using synthetic peptides, the 15G4 epitope was localized to the sequence 297-310 in the V3 variable region. This indicates that the flexibility of the V3 region, which delimits the C-terminus of the regulatory domain, may not be necessary for the allosteric activation of PKC. In view of these results, we propose that PKC activation by its cofactors results in intramolecular changes which allow the enzyme to bind exogenous substrates.

Amino Acid Sequence

Protein kinase C heterogeneity in GH4C1 rat pituitary cells. Characterization of a Ca2(+)-independent phorbol ester receptor.

Clonal GH4C1 rat pituitary cells are heterogeneous with respect to phorbol dibutyrate receptors (PDBu-R) and protein kinase C (PKC) content. GH cell PDBu-Rs can be separated into two categories based on Ca2(+)-modulation of receptor affinity. Approximately 70% of the cytosolic PDBu-Rs demonstrate Ca2(+)-sensitive receptor affinity and redistribute from the soluble to the particulate fraction in the presence of excess Ca2+. The other 30% of the receptors remain in the cytosol in the presence of excess Ca2+. Their receptor affinity is Ca2(+)-independent. Northern blot hybridization and immunoblot analysis showed that GH4C1 cells express Ca2(+)-independent epsilon-PKC as well as Ca2(+)-dependent alpha- and beta-PKCs. Cell lysis in Ca2+ caused the redistribution of greater than 95% of alpha- and beta-PKC to the particulate fraction, whereas approximately 90% of the epsilon-PKC remained in the cytosol. In contrast, brief treatment of GH cell cultures with PDBu or thyrotropin-releasing hormone caused redistribution of all three isozymes. Prolonged treatment with PDBu down-modulated all three isozymes but at different rates and to different extents. In contrast, prolonged thyrotropin-releasing hormone treatment selectively down-modulated epsilon-PKC. These results demonstrate that GH cells have both Ca2(+)-sensitive and -insensitive PKCs and PDBu-Rs and that both populations are regulated by agonists that control prolactin synthesis and secretion by these cells.

Animals

Heterogeneity of protein kinase C expression and regulation in T lymphocytes.

The purpose of the present study was to examine protein kinase C (PKC) isotype expression in T lymphoblasts derived from peripheral blood and the T leukaemic cell Jurkat. Using antisera reactive with PKC alpha, beta 1, and beta 2 and gamma, it was observed that T cells expressed two PKC isotypes, PKC alpha and beta 1. No PKC gamma was detected in T lymphocytes. In lymphoblasts, high levels of PKC beta compared to PKC alpha were found whereas Jurkat cells expressed high levels of alpha compared to PKC beta. Differences in the calcium sensitivity of phorbol ester-induced phosphorylation were observed in Jurkat and T lymphoblasts which correlated with the relative levels of PKC alpha and beta isotypes expressed by the cells.

Antigens, Differentiation, T-Lymphocyte

A novel inositol-phospholipid-specific phospholipase C. Rapid purification and characterization.

A novel bovine brain inositol-phospholipid-specific phospholipase C has been identified on the basis of chromatographic behaviour and purified to apparent homogeneity by a rapid three-step procedure. The purified enzyme has a molecular mass of 85 kDa on SDS/polyacrylamide gel electrophoresis and a specific activity of 24 mumol.min-1.mg-1. The enzyme is dependent on Ca2+ and shows a marked preference for inositol phospholipid substrates. The unique nature of this polypeptide was confirmed through partial protein sequence analysis.

Amino Acid Sequence

Monoclonal antibodies to protein kinase C gamma. Functional relationship between epitopes and cofactor binding sites.

Four monoclonal antibodies (mAbs), derived from high-responder Biozzi mice immunized with purified protein kinase C, were selected by ELISA and further characterized by immunoblot: 3G12, 5A2, 36G9 are of isotype gamma 1, kappa and 15G4 is of isotype gamma 2b, kappa. Competition analysis between 15G4 and the three other mAbs showed that 15G4 and 3G12 are directed against either the same or overlapping epitope(s). All four mAbs are specific for the bovine gamma isoform of protein kinase C and cross-react with protein kinase C gamma from a variety of animal species. Immunoblot analysis of protein kinase C tryptic fragments revealed that the mAbs recognize the regulatory domain and not the catalytic domain. Two of the mAbs, 36G9 and 5A2, inhibit protein kinase C gamma cofactor-dependent activity (80% and 50% respectively). Consistent with the epitope mapping, none of mAbs inhibit the cofactor-independent catalytic activity of protein kinase C gamma. Competition analysis between these mAbs and phosphatidylserine, 12-O-tetradecanoylphorbol 13-acetate and Ca2+ showed that 36G9 and 5A2 block cofactor binding to protein kinase C gamma. These four mAbs thus interact with at least three distinct epitopes in the regulatory domain of protein kinase C gamma.

Animals

Pyomyositis in a child with acquired immunodeficiency syndrome. Patient report and brief review.

Although common in tropical regions, pyomyositis is rare in the continental United States. Fewer than 50 cases have been reported to date. It is characterized by suppuration of large muscle groups that can, if not quickly and appropriately treated, lead to sepsis and death. Diagnosis can be difficult secondary to the atypical appearance of the abscess process early on. Almost all cases have occurred in otherwise healthy people. The simultaneous occurrence of pyomyositis and immunodeficiency is rare. A recent report of a case in an adult with the acquired immunodeficiency syndrome (AIDS) is not, however, unexpected. We describe the first documented occurrence of pyomyositis in a child with AIDS. A brief review of the topic is included. Pyomyositis should be included in the list of unusual infections that can occur in children with AIDS.

Acquired Immunodeficiency Syndrome

Evidence that protein kinase C differentially regulates the human T lymphocyte CD2 and CD3 surface antigens.

The purpose of the present study was to explore the effects of protein kinase C (PKC) stimulation on two cell surface receptors that regulate T cell growth: the T cell antigen receptor/CD3 complex and the CD2 antigen. The data show that PKC differentially regulates the expression and functions of CD2 and CD3 molecules. Thus, activation of PKC induced a decrease in cell surface levels of CD3 molecules but an increase in the expression of CD2 antigens. Additionally, prolonged stimulation of PKC inhibited subsequent T cell activation via CD3 but promoted activation via CD2 molecules. These results suggest that the CD2 cellular activation pathway would be preferred in T cells which have been exposed to stimulators of PKC. The molecular basis for the regulatory effects of PKC on CD3 and CD2 molecules and its physiological significance are discussed.

Antibodies, Monoclonal

Medulloblastoma in association with the Coffin-Siris syndrome.

An 8-year old patient with Coffin-Siris syndrome is presented, who was found to have a medulloblastoma during the evaluation of apnea and ventilator dependency. Although several cases of Dandy Walker cysts and one case of brain-stem heterotopia have been described in this rare syndrome, this is the first report of medulloblastoma in a patient with Coffin-Siris syndrome. Possible pathogenetic mechanisms are briefly discussed.

Abnormalities, Multiple