The second two hundred cases of endocapsular phacoemulsification: the learning curve levels off.
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Cataract Extraction↗
Biomedical subjects
S Alexander
Publications and source records attributed to S Alexander.
The PsB glycoprotein complex is secreted as a preassembled precursor of the spore coat in Dictyostelium discoideum.
The PsB glycoprotein in Dictyostelium discoideum is one of a diverse group of developmentally regulated, prespore-cell-specific proteins, that contain a common O-linked oligosaccharide. This post-translational modification is dependent on the wild-type modB allele. The PsB protein exists as part of a multiprotein complex of six different proteins, which have different post-translational modifications and are held together by both covalent and non-covalent interactions (Watson et al. (1993). J. Biol. Chem. 268, 22634-22641). In this study we have used microscopic and biochemical analyses to examine the cellular localization and function of the PsB complex during development. We found that the PsB complex first accumulates in prespore vesicles in slug cells and is secreted later during culmination and becomes localized to both the extracellular matrix of the apical spore mass of mature fruiting bodies and to the inner layer of the spore coat. The PsB associated with the spore coat is covalently bound by disulfide bridges. The PsB protein always exists in a multiprotein complex, but the composition of the PsB complex changes during secretion and spore maturation. Some of the PsB complex proteins have been identified as spore coat proteins. These data demonstrate that some of the proteins that form the spore coat exist as a preassembled precursor complex. The PsB complex is secreted in a developmentally regulated manner during the process of spore differentiation, at which time proteins of the complex, as well as additional spore coat proteins, become covalently associated in at least two forms of extracellular matrix: the interspore matrix and the spore coat. These and other studies show that proteins with modB dependent O-linked oligosaccharides are involved in a wide variety of processes underlying morphogenesis in this organism. These developmental processes are the direct result of cellular mechanisms regulating protein targeting, assembly and secretion, and the assembly of specific extracellular matrices.
Animals↗
Population-based study of HIV-1 infection in 4,086 subjects in northwest Tanzania.
A population-based HIV-1 seroprevalence survey of 4,086 individuals, aged 15-49 years, in the North Mara district of Tanzania from rural, periurban, and urban areas, including high-risk (prostitutes, and co-workers) individuals, was performed in 1989 and 1990. The overall seroprevalence was 7.3% (95% confidence interval, 6.5-8.1), with a gradient of seropositivity from high-risk 13.0% (9.1, 16.8), urban 8.8% (7.6, 10.0), periurban 6.5% (4.7, 8.4), to rural 2.6% (1.6, 3.7) subjects. Adjusted for population group, HIV-1 seroprevalence was significantly elevated for men over age 24 and for women 20-34 years old, while age-specific prevalence rates were similar for men and women in the rural area. Recent treponemal infection, measured by the rapid plasma reagin test, was not associated with HIV-1 seropositivity in men or women. These data suggest a growing HIV-1 epidemic paralleling rising rates in other rural areas of Africa distant from areas that have been previously recognized as having high prevalence.
Adolescent↗
A developmentally regulated glycoprotein complex from Dictyostelium discoideum.
The monoclonal antibody MUD50 recognizes an epitope on a family of developmentally regulated proteins in Dictyostelium discoideum (Alexander, S., Smith, E., Davis, L., Gooley, A., Por, S. B., Browne, L., and Williams, K. L. (1988) Differentiation 38, 82-90). This epitope is an O-linked oligosaccharide that requires the wild-type modB allele for expression. These glycoproteins are structurally diverse. Some are integral membrane proteins, while others are soluble and do not require detergent for solubilization. One of the soluble glycoproteins, PsB, is also recognized by the monoclonal antibody MUD102, which binds to the polypeptide backbone. The antibody recognizes a single 100-kDa band in Western analysis. In this report we demonstrate that the PsB molecule is part of a specific developmentally regulated multiprotein complex containing six different proteins. The complex is held together by both covalent and noncovalent bonds. Interestingly, only the PsB glycoprotein has the MUD50 O-linked oligosaccharide determinant. None of the proteins in the complex is N-glycosylated as assessed by sensitivity to peptide N-glycosidase F. Only one of the complex proteins is heavily phosphorylated. This work establishes the foundation for additional studies on the biosynthesis, processing, and assembly of the O-glycosylated PsB protein.
Animals↗
Human T-cell leukemia virus type II infection frequently goes undetected in contemporary US blood donors.
Serologic screening for human T-cell leukemia virus type I (HTLV-I) infection was begun in US blood banks with the licensure of enzyme-linked immunosorbent assays (ELISA) in December 1988. We examined the donation histories of the first 60 Western blot (WB)-confirmed HTLV-I/II positive donors to one blood center and found 8 had made 16 previous donations that scored negative on the screening ELISA. All 16 donations had ELISA absorbance below the cutoff for a positive assay, but still well above that of the average donation (17.6% +/- 5.7% of the cutoff). In a more extensive study, 17 donations from a total of 61,752 at six blood centers were both ELISA-positive and WB-positive for HTLV-I (4) or HTLV-II (13), and 218 samples had ELISA absorbance greater than 50% of the ELISA cutoff. One hundred seventy-eight of the 218 were tested further by WB and 11 were found positive. All 11 positives were confirmed by polymerase chain reaction; 10 had HTLV-II and 1 had HTLV-I. Thus, the HTLV-I-based screening ELISA missed at least 10 of 23, or 43% (95% confidence interval, 23% to 66%), of HTLV-II infections, compared with 1 of 5, or 20%, of HTLV-I infections.
Blood Donors↗
Domain mapping of tube, a protein essential for dorsoventral patterning of the Drosophila embryo.
The tube protein plays an essential role in the signal transduction pathway that establishes dorsoventral polarity in the Drosophila melanogaster embryo. Characterization of each of four tube mutants revealed a substitution or insertion in the amino-terminal half of the protein. This portion of the tube protein is also evolutionarily conserved, as demonstrated by isolation and sequencing of the Drosophila virilis tube gene. Moreover, RNA microinjection assays and germline transformation experiments demonstrated that the amino-terminal domain alone provides substantial levels of gene function: constructs encoding only the amino-terminal domain restore dorsoventral polarity to embryos lacking any maternal tube function. In the carboxyterminal domain, sequence conservation is concentrated in the five octapeptide repeats. Although the repeat-containing domain by itself provides no rescue of the tube maternal effect phenotype, it is necessary for wild-type levels of tube activity. This domain is thus likely to play an ancillary role in axis formation.
Amino Acid Sequence↗
Maintenance immunosuppression therapy and outcome of renal transplantation in North American children--a report of the North American Pediatric Renal Transplant Cooperative Study.
The North American Pediatric Renal Transplant Cooperative Study collects extensive data on all transplants entered into its registry. For this study we evaluated 568 cadaver kidney and 492 live-donor recipients with graft function at 30 days post transplant. Utilizing maintenance immunosuppressive therapy at 30 days post transplant, we evaluated patient and graft outcome, mortality and morbidity over the first 6 months post transplant. For cadaver kidney recipients, 36 patients were receiving prednisone and azathioprine (PA), 114 were maintained on prednisone and cyclosporine (PC) and 418 were on prednisone, cyclosporine and azathioprine (PCA). Patients receiving PA had a greater incidence of rejection prior to 30 days, a greater incidence of hospitalization for rejection and for hypertension over the next 6 months and a greater loss of allograft in the first 6 months compared with the other two groups. The only difference noted between PC and PCA was a lower serum creatinine in the PCA group at 6 months. For living-related kidney recipients, there were 78 patients maintained on PA, 97 on PC and 317 on PCA. Again patients receiving PA had a higher rate of hospitalization for rejection and a higher rate of graft loss. When patients receiving PC were compared with those receiving PCA, no differences were noted in the 6-month serum creatinine values, but a greater percentage of PCA patients were receiving antibiotics on day 30. We conclude that PA is poor therapy for both groups, PCA is ideal therapy for cadaver kidney recipients, but no beneficial effects are noted when PCA is used over PC for live-related donor kidney transplants.
Adolescent↗
Pharmacological characterisation of the calcium channels coupled to the plateau phase of KCl-induced intracellular free Ca2+ elevation in chicken and rat synaptosomes.
The effect of various blockers of voltage operated calcium channels (VOCCs) was studied on the non-inactivating, plateau phase of KCl-induced intracellular free Ca2+ ([Ca2+]i) elevation in rat cortical and chicken forebrain synaptosomes. In chicken synaptosomes, omega-CgTx GVIA (0.1 nM to 1 microM) and omega-CgTx MVIIA (0.1 nM to 1 microM), both selective blockers of N-type Ca2+ channels, produced a concentration-dependent inhibition of the plateau phase of [Ca2+]i elevation. omega-CgTx GVIA (IC50 value 28 nM) was more potent than omega-CgTx MVIIA (IC50 value 78 nM), but at submaximal concentrations, took longer to reach its maximum effect (20 min for omega-CgTx GVIA; 10 min for omega-CgTx MVIIA). At 1 microM, the highest concentration tested, each toxin blocked > 85% of [Ca2+]i elevation. The effect of omega-CgTx GVIA on the extent and time-course of inhibition of [Ca2+]i elevation was maintained in a Na(+)-free, choline substituted, medium. omega-Aga IVA (300 nM), a selective blocker of P-type calcium channels, inhibited 28 +/- 5% of [Ca2+]i elevation. The effect of a combination of submaximal inhibitory concentrations of omega-CgTx GVIA (100 nM) and omega-Aga IVA (300 nM) was less than additive. In rat synaptosomes, omega-CgTx GVIA (1 microM) and omega-CgTx MVIIA (1 microM), blocked only 18 +/- 5% and 17 +/- 4% of the plateau phase of free Ca2+ elevation, respectively. omega-Aga IVA produced a concentration-dependent inhibition of [Ca2+]i elevation in this preparation. Threshold inhibition was observed at 1 nM, and maximum inhibition (64 +/- 8%) at 1 microM.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Factors predictive of sustained growth in children after renal transplantation. The North American Pediatric Renal Transplant Cooperative Study.
To ascertain growth and rehabilitation of children after transplantation, the North American Pediatric Renal Transplant Cooperative Study collected growth data on renal transplant recipients. From January 1987 through December 1990, a total of 1553 children with one or more transplants were entered into the study by its 75 participating centers. Of these, the first 300 children with a functioning graft and 2 years of linear growth data form the cohort for this study. For the total cohort of 300 patients, the mean (+/- SEM) baseline height z score was -2.41 +/- 0.09, and the change in z score determined after 2 years was 0.18 +/- 0.06 (p < 0.01). Children in the age group from birth to 1 year had the maximal deficit and had the maximal improvement in z score, gaining about 1 SD (p < 0.01). For the 2- to 5-year-old group, the change in z score was about 0.5 SD (p < 0.001). No improvement in z score was noted for children 6 to 17 years of age. Each increase in serum creatinine concentration of 90 mumol/L (1 mg/dl) was associated with -0.17 decrease in the z score (p < 0.001). Gender, donor source, history of previous transplantation, and prior dialysis were not associated with a significant change in the z score; thus the increased rate of growth during the first 2 post-transplantation years occurred mainly in subjects less than 6 years of age.
Adolescent↗
Captopril inhibits the 72 kDa and 92 kDa matrix metalloproteinases.
Gelatinases are metalloproteinases in the kidney which can cleave type IV collagen as well as gelatin. We partially purified the 72 kDa and 92 kDa gelatinases. The gelatinolytic activity was measured by zymography and a quantitative biotin-avidin assay. By zymography, captopril in concentrations of 20 mM and 40 mM added to the incubation buffer reduced the gelatinolytic activity in a dose-dependent manner. The addition of zinc in a concentration of 50 to 100 microM reversed most of the inhibitory effect of captopril. By the biotin-avidin assay, captopril in a concentration of 30 to 50 nM reduced half of either the 72 kDa or 92 kDa gelatinolytic activity. Zinc in a concentration of 50 microM completely reversed the inhibitory effect of 1 microM captopril on both gelatinases. Lisinopril, a non-sulfhydryl ACE inhibitor, similarly inhibited the gelatinases, but a 100-fold higher concentration of the drug was needed. These findings suggest that captopril reversibly inhibits the 72 kDa and 92 kDa metalloproteinases by interacting with the zinc ion at their active sites. This inhibitory effect is observed with captopril levels comparable to the concentrations needed to inhibit the angiotensin converting enzyme in vivo and may at least partially explain some of the renoprotective effects seen with this drug.
Animals↗
Toward a molecular genetic analysis of spermatogenesis in Drosophila melanogaster: characterization of male-sterile mutants generated by single P element mutagenesis.
We describe 83 recessive autosomal male-sterile mutations, generated by single P element mutagenesis in Drosophila melanogaster. Each mutation has been localized to a lettered subdivision of the polytene map. Reversion analyses, as well as complementation tests using available chromosomal deficiencies, indicate that the insertions are responsible for the mutant phenotypes. These mutations represent 63 complementation groups, 58 of which are required for spermatogenesis. Phenotypes of the spermatogenesis mutants were analyzed by light microscopy. Mutations in 12 loci affect germline proliferation, spermatocyte growth, or meiosis. Mutations in 46 other loci disrupt differentiation and maturation of spermatids into motile sperm. This collection of male-sterile mutants provides the basis for a molecular genetic analysis of spermatogenesis.
Animals↗
Leukaemia arising in donor cells following allogeneic bone marrow transplantation for beta thalassaemia demonstrated by immunological, DNA and molecular cytogenetic analysis.
Combined DNA analysis, molecular cytogenetic and immunological techniques have been used to identify the donor origin of common acute lymphoblastic leukaemia (cALL) which arose in a male patient with beta thalassaemia major, 5 years after an allogeneic bone marrow transplant from his HLA-matched sister. The necessity of using multiple techniques in this and similar cases is emphasized and the possible mechanisms for the development of donor leukaemia and the leukaemic transformation of donor cells are discussed.
Bone Marrow↗
Evaluation of EMIT Cyclosporine Assay for use with whole blood.
We evaluated the EMIT Cyclosporine Assay, designed for specific quantification of cyclosporine (CsA) in whole blood. The assay was run on the Roche Cobas Mira or Cobas Mira S analyzer. Analytical recovery from both normal donor whole blood and transplant patients' samples was within 17% of the standards. Measurement of diluted out-of-range samples also yielded excellent recovery (101-105%). Within-run, between-run, and total CVs were < or = 8.1%, 10.9%, and 12.1%, respectively. The detection limit was < 32 micrograms/L. The assay was linear from 0 to 500 micrograms/L. No significant cross-reactivity was observed for CsA metabolites AM1, AM19, and AM4N. Slight cross-reactivity occurred with metabolite AM9; 670 micrograms/L AM9 increased the measured CsA concentration by 49 micrograms/L. High concentrations of bilirubin, uric acid, triglycerides, and cholesterol, as well as 54 commonly coadministered drugs did not interfere with CsA quantification. Similarly, neither extreme values of hematocrit nor choice of anticoagulant affected CsA recovery. Sample extract stability was > 4 h, and assay calibration was stable for at least 2 weeks. Patients' samples analyzed by the EMIT assay showed strong correlation with both HPLC and 125I-RIA (r > 0.97). We conclude that the EMIT Cyclosporine Assay provides a convenient, accurate, and precise method for specific quantification of CsA in whole blood.
Calibration↗
Prospective evaluation of one surgeon's first 100 cases of endocapsular phacoemulsification cataract surgery.
In this series of one surgeon's first 100 cases of endocapsular phacoemulsification cataract surgery (EPECS), believed to be the first truly prospective study of its kind, 86% of patients achieved corrected vision of 6/6 to 6/4; 96% achieved vision of 6/12 or better; and excluding those with pre-existing pathology, 99% achieved 6/12. Posterior capsular rupture occurred in 11 cases, with vitrectomy being required in eight cases. Detailed analysis of the 100 cases is provided.
Adult↗
Altering the antigenicity of proteins.
To better understand the binding interaction between antigen and antibody we need to distinguish protein residues critical to the binding energy and mechanism from residues merely localized in the interface. By analyzing the binding of monoclonal antibodies to recombinant wild-type and mutant myohemerythrin (MHr) proteins, we were able to test the role of individual critical residues at the highly antigenic site MHr-(79-84), within the context of the folded protein. The results directly show the existence of antigenically critical residues, whose mutations significantly reduce antibody binding to the folded protein, thus verifying peptide-based assignments of these critical residues and demonstrating the ability of buried side chains to influence antigenicity. Taken together, these results (i) distinguish the antigenic surface from the solvent-exposed protein surface before binding, (ii) support a two-stage interaction mechanism allowing inducible changes in protein antigens by antibody binding, and (iii) show that protein antigenicity can be significantly reduced by alteration of single critical residues without destroying biological activity.
Amino Acid Sequence↗
Chronic neurodegenerative disease associated with HTLV-II infection.
Although human T-cell leukemia virus (HTLV) type I is known to cause a number of diseases, there has been no convincing evidence of pathological changes after infection with the related virus, HTLV-II. We have found an endemic focus of HTLV-II infection among members of an American Indian population in New Mexico, USA. We set out to determine the pathological consequences of HTLV-II infection in this population and identified two sisters (aged 59 and 46 years) with a disease superficially resembling the myeloneuropathy induced by HTLV-I. These women had a syndrome similar to the olivopontocerebellar atrophy variant of multiple system atrophy, and HTLV-II infection was confirmed by western blot and the polymerase chain reaction. Thus, HTLV-II may, like HTLV-I, cause a progressive neurodegenerative disease.
Ataxia↗
Discoidin proteins of Dictyostelium are necessary for normal cytoskeletal organization and cellular morphology during aggregation.
The onset of aggregation of bacterially-grown Dictyostelium discoideum amoebae is accompanied by the accumulation of the discoidin proteins. An immunofluorescent analysis demonstrates that discoidin is distributed throughout the cytoplasm, but is excluded from vesicles and nucleoli. There is no indication of either extracellular or membrane localization. Translocating amoebae of mutants lacking discoidin form more dispersed pseudopodial regions at the cell periphery, possess an abnormally centered microtubule organizing center, are blunt rather than elongate, and lack the tapered posterior uropod characteristic of translocating wild-type cells. However, in spite of the loss of the normal elongate morphology, discoidinless mutants translocate with instantaneous velocities and directional persistence comparable to wild-type cells, and they respond normally to the rapid addition of cAMP. These results demonstrate that the discoidin proteins are cytoplasmic components essential for the maintenance of the elongate cell morphology, cytoskeletal organization and the ability to align with other cells during aggregation. However, the elongate morphology is not a requisite for rapid and persistent single cell translocation.
Actins↗