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Biomedical subjects

J Kaplan

Publications and source records attributed to J Kaplan.

At least 145 records · Page 8Linked to original sources
PubMed1997

Contraceptive efficacy of norethindrone encapsulated in injectable biodegradable poly-dl-lactide-co-glycolide microspheres (NET-90): phase III clinical study.

Safety, contraceptive efficacy, and acceptability of norethindrone, encapsulated in biodegradable poly-dl-lactide-co-glycolide injectable microspheres (NET-90), was evaluated for 12 months in one hundred women. Fifty-one volunteers received 65 mg, and 49 received 100 mg of NET-90, at three month intervals, intramuscularly in the gluteal region. The mean NET levels at 3-month intervals for the 65 and 100 mg groups were, respectively, 0.32 +/- 0.16 ng/ml and 0.49 +/- 0.25 ng/ml. No local or systemic side-effects were observed in either group. Body weight, blood pressure, and laboratory parameters, namely hemoglobin, hematocrit, lipid profile, sequential multichannel autoanalyzer computer profiles (SMAC), as well as PAP smear, remained within normal limits throughout the study in both groups. There was no pregnancy in the 65 mg group; however, one volunteer became pregnant in the 100 mg group. In the 65 mg group, 52.9% of menstrual cycles were normal, 34.5% were amenorrheic, and 12.6% showed prolonged bleeding. In the 100 mg group, 40.6% of the cycles were normal, 52.3% were amenorrheic, and 7.1% had episodes of prolonged bleeding. A total of 40.3% and 36.6% of the cycles showed increased spotting in the 65 and 100 mg group, respectively. Our observations indicate that NET-90 microsphere injectables can provide a safe, efficacious, and acceptable method of contraception.

Adult↗
PubMed1997

Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB.

Usher syndrome is recognized as the most frequent cause of hereditary deaf-blindness. Usher syndrome type I (USH1), the most severe form of the disease, is characterized by profound congenital sensorineural deafness, constant vestibular dysfunction, and retinitis pigmentosa of prepubertal onset. This form is genetically heterogeneous and five loci (USH1A-E) have been mapped thusfar. However, only the gene responsible for USH1 B (which accounts for approximately 75% of USH1 cases) has been characterized. It encodes a long-tailed unconventional myosin, myosin VIIA, with a predicted 2215 amino acid sequence. Primers covering the complete myosin VIIA coding sequence as well as the 3' non coding sequence were designed, allowing direct sequence analysis of each of the 48 coding exons and flanking splice sites in seven patients affected by USH1. Four novel mutations were thereby identified. The possibility should now be considered of a sequence-based prenatal diagnosis in some of the families affected by this very severe form of Usher syndrome.

Base Sequence↗
PubMed1997

A newly identified locus for Usher syndrome type I, USH1E, maps to chromosome 21q21.

Usher syndrome (USH) is a clinically and genetically heterogeneous disorder characterized by congenital hearing loss combined with retinitis pigmentosa. This dual sensorineural deficiency is transmitted in an autosomal recessive mode. Usher syndrome type I (USH1) is the most severe form. Four loci responsible for USH1 (USH1A, 1B, 1C and 1D) have previously been mapped, among which only the USH1B gene has been cloned. Using homozygosity mapping in a consanguineous family from Morocco, we identified a novel locus for USH1, USH1E, mapping to chromosome band 21q21. The delimited 15 cM interval is flanked by the loci D21S1905 and D21S1913. Subsequent segregation analysis of two families affected by USH1, in which the A, B, C and D loci had been excluded, also excluded the involvement of the USH1E locus, therefore indicating the existence of at least one more locus for USH1.

Child↗
PubMed1997

Severe manifestations in carrier females in X linked retinitis pigmentosa.

Retinitis pigmentosa (RP) is a group of progressive hereditary disorders of the retina in which various modes of inheritance have been described. Here, we report on X linked RP in nine families with constant and severe expression in carrier females. In our series, however, the phenotype was milder and delayed in carrier females compared to hemizygous males. This form of X linked RP could be regarded therefore as partially dominant. The disease gene maps to chromosome Xp2.1 in the genetic interval encompassing the RP3 locus (Zmax=13.71 at the DXS1100 locus). Single strand conformation polymorphism and direct sequence analysis of the retinitis pigmentosa GTPase regulator (RPGR) gene, which accounts for RP3, failed to detect any mutation in our families. Future advances in the identification of X linked RP genes will hopefully help to elucidate the molecular basis of this X linked dominant RP.

Adolescent↗
PubMed1997

Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans.

We have utilized an experimental model of human zinc deficiency for study of cytokines production by TH1 and TH2 cells. Additionally, we determined ratios of CD4+ to CD8+ and CD4+ CD45RA+ to CD4+CD45RO+ cells and percentages of CD73+ T cytolytic cells in the CD8+ subset. The data were collected during baseline, at the end of the zinc-restricted period, and following zinc repletion. Our results showed that functions of TH1 cells, as evidenced by production of interferon-gamma, interleukin-2 (IL-2), and tumor necrosis factor-alpha, were decreased, whereas functions of TH2 cells (production of IL-4, IL-6, and IL-10) were unaffected by zinc deficiency. Thus an imbalance between TH1 and TH2 cells resulted because of zinc deficiency in humans. Our studies also showed that zinc may be required for regeneration of new CD4+ T lymphocytes and maintenance of T cytolytic cells. We conclude that an imbalance between TH1 and TH2 cells, decreased recruitment of T naive cells, and decreased percentage of T cytolytic cells may account for decreased cell-mediated immune functions in zinc-deficient subjects.

Adult↗
PubMed1997

HTLV-associated myelopathy in a cohort of HTLV-I and HTLV-II-infected blood donors. The REDS investigators.

OBJECTIVE: HTLV-I-associated myelopathy (HAM) is a slowly progressive spastic paraparesis caused by infection with human T-lymphotropic virus type I (HTLV-I). The prevalence of HAM among those infected with HTLV-I is poorly defined, and the association of a similar myelopathy with HTLV-II infection has not been confirmed. DESIGN: Cross-sectional examination of HTLV-I, HTLV-II, and control subjects from the baseline visit of a cohort study. SETTING/ SUBJECTS: Persons testing HTLV seropositive at the time of blood donation at five U.S. blood centers, their seropositive sex partners, and a matched control group of HTLV seronegative blood donors. MEASUREMENTS: HTLV-I and HTLV-II were differentiated by serology and/or polymerase chain reaction. All subjects received systematic neurologic screening examinations. RESULTS: A diagnosis of myelopathy was confirmed in four of 166 HTLV-I subjects (2.4%, 95% confidence interval 0.7%, 6.1%) and in one of 404 HTLV-II subjects (0.25%, 95% confidence interval 0.0%, 0.6%). None of the 798 controls had a similar myelopathy, although one had longstanding typical multiple sclerosis. CONCLUSIONS: Our data also suggest that HAM occurs more frequently among HTLV-I-infected subjects than reported by previous studies. The HTLV-II infected myelopathy patient identified in this cohort, together with three other case reports in the literature, implies a pathogenic role for this human retrovirus. The diagnosis of HTLV-associated myelopathy should be considered in cases of spastic paraparesis or neurogenic bladder when risk factors for HTLV-I or HTLV-II infection are present.

AIDS Serodiagnosis↗
PubMed1997

Identification of a heparin binding peptide on the extracellular domain of the KDR VEGF receptor.

Vascular endothelial growth factor (VEGF), a potent and specific activator of endothelial cells, is expressed as multiple homodimeric forms resulting from alternative RNA splicing. VEGF121 does not bind heparin while the other three isoforms do, and it has been documented that the binding of VEGF165 to its receptor is dependent upon cell surface heparin sulfate proteoglycans. Little is known about the biochemical mechanism that allows for heparin regulation of growth factor binding. For example, it is not clear whether heparin interactions with growth factor or with cell surface receptors or both are essential for VEGF binding to its receptor. In this manuscript we provide results which are consistent with the hypothesis that an interaction between heparin and a site on the KDR receptor subtype is essential for VEGF165 binding. First, we demonstrate that expression of KDR into a CHO cell line deficient in heparan sulfate biosynthesis does not allow VEGF165 binding unless heparin is exogenously added during the binding assay. Secondly, we show that a ten amino acid synthetic peptide, corresponding to a sequence from the extracellular domain of the KDR, both inhibits VEGF165 binding to the receptor and also binds heparin with high avidity. Third, affinity purification of heparin molecules on a KDR-derived peptide affinity column, together with capillary electrophoresis and polyacrylamide electrophoresis analysis, was used to show that the KDR-derived peptide interacts with a specific subset of polysaccharide chains contained in the unfractionated heparin. Taken together, these results are consistent with the hypothesis that interactions between cell surface heparan sulfate proteoglycans and the VEGF receptor contribute to allowing maximal VEGF binding.

Animals↗
PubMed1997

Zinc deficiency: changes in cytokine production and T-cell subpopulations in patients with head and neck cancer and in noncancer subjects.

Cell-mediated immune dysfunctions and susceptibility to infections have been observed in zinc-deficient human subjects. In this study, we investigated the production of cytokines and characterized the T-cell subpopulations in three groups of mildly zinc-deficient subjects. These included head and neck cancer patients, healthy volunteers who were found to have a dietary deficiency of zinc, and healthy volunteers in whom we induced zinc deficiency experimentally by dietary means. We used cellular zinc criteria for the diagnosis of zinc deficiency. We assayed enzyme-linked immunosorbent assay the production of cytokines from phytohemagglutinin-stimulated peripheral blood mononuclear cells and assessed by flow cytometry the differences in T-cell subpopulations. Our studies showed that the cytokines produced by TH1 cells were particularly sensitive to zinc status, inasmuch as the production of interleukin-2 (IL-2) and interferon-gamma were decreased even though the deficiency of zinc was mild in our subjects. TH2 cytokines (IL-4, IL-5, and IL-6) were not affected by zinc deficiency. Natural killer cell lytic activity also was decreased in zinc-deficient subjects. Recruitment of naive T cells (CD4+CD45 RA+) and CD8+ CD73+ CD11b-, precursors of cytolytic T cells, were decreased in mildly zinc-deficient subjects. An imbalance between the functions of TH1 and TH2 cells and changes in T-cell subpopulations are most probably responsible for cell-mediated immune dysfunctions in zinc deficiency.

Adult↗
PubMed1997

Minor advocacy in healthcare: a proposal for a more efficient solution.

Autonomy is a crucial, yet litigious right in health care that is usually unquestioned in the case of adults. However, children's or their guardian's refusal to accept necessary medical care can expedite the question of autonomy from the medical to the legal arena. Therefore, to save time, money, and lives, the health care establishment, specifically ethics committees, must be given rights as a judicial body to hand down binding judgments in cases of minors refusing the medical community's standard of care.

Adolescent↗
PubMed1996

Analysis of three deletion breakpoints in Xp21.1 and the further localization of RP3.

The gene responsible for X-linked retinitis pigmentosa (xlRP) in Xp21.1 (RP3) was initially localized by deletion analysis to within a 150- to 170-kb region between the CYBB locus and the proximal deletion junction (BBJPROX) from a patient, BB, who suffered from Duchenne muscular dystrophy (DMD), McLeod syndrome, chronic granulomatous disease (CGD), and xlRP. This gene has recently been isolated and was found to be located outside and 400 kb proximal to the BB deletion. Further analysis of BBJPROX has identified the breakpoint junction sequence, showing that it occurs within an Alu repetitive element on the proximal side but with no significant homology to the distal sequence in dystrophin intron 30. Analysis of an overlapping deletion in patient NF, who suffered from DMD, CGD, and McLeod syndrome, shows that this deletion is within 4 kb but extends centromeric to BBJPROX, consistent with the location of RP3 outside the BB deletion region. A sequence with strong homology to a THE-1 transposon-like element was identified 7-13 kb from the proximal BB and NF breakpoints. These elements have been implicated in several highly unstable genomic regions. A third overlapping deletion, in a patient, SB, who suffered from CGD, McLeod syndrome, and xlRP, has here been shown to extend 380 kb proximal to the NF breakpoint, consistent with the finding that RP3 lies outside the BB deletion. This deletion has now been shown to disrupt the RP3 (RPGR) gene. The reason for the retinitis pigmentosa phenotype in patient BB remains unclear, but the most likely explanations include a long-range chromosomal position effect, a small secondary rearrangement, and the presence of a coincident autosomal form of retinitis pigmentosa.

Base Sequence↗
PubMed1996

Natural killer cell recognition of "self" and "non-self" triggering antigens on normal lymphoblasts.

NK cell specificity for normal lymphoblasts was tested in mice by direct cytotoxicity and competitive inhibition assays. IL-2-activated NK cells lysed Hh-1 incompatible but not Hh-1 compatible or Hh-1[null] allogeneic and semisyngeneic lymphoblasts. NK cells also lysed some syngeneic blasts. NK alloreactivity was inhibited by unlabeled targets which shared at least one Hh-1 determinant with the labeled target. NK self-reactivity was inhibited by syngeneic cells as well as by some allogeneic cells. Class I molecule-deficient beta2m-/- blasts universally inhibited NK lysis of all normal blasts. Cold targets appeared to specifically inhibit NK lysis by competing for recognition by NK activatory receptors rather than by competing for NK lysis by sharing with hot targets the absence of MHC class I inhibitory molecules recognized by NK cell Ly49 molecules. Backcross analysis revealed that a single non-MHC-linked gene locus regulates the accessibility of some normal lymphoblast target antigens to recognition by triggering receptors on self-reactive BALB/c NK cells. The results suggest that target lymphoblast class I molecules may differentially control the accessibility of universally expressed polymorphic NK triggering antigens to positive recognition by distinct sets of alloreactive and self-reactive NK cells.

Animals↗
PubMed1996

Characterization of yeast methyl sterol oxidase (ERG25) and identification of a human homologue.

A yeast mutant (LT06) was isolated that showed no growth on iron-limited medium but normal growth on iron-replete medium. A gene cloned from a genomic yeast library complemented the defect, allowing growth on low iron medium. Allelic segregation analysis demonstrated that the cloned gene was the normal allele rather than a high copy suppressor. A disruption mutant was nonviable, indicating that the gene was essential. Sequence analysis and functional assays indicated that the cloned gene was identical to ERG25, a gene that codes for methyl sterol oxidase. Incubation of LT06 in low iron medium resulted in marked changes in lipid metabolism, including the accumulation of fatty acids, triglycerides, methyl sterols, and other sterol precursors. A human homologue of ERG25 was cloned, sequenced, and mapped to human chromosome 4q32-34. Analysis of the data base with both ERG25 and the human homologue resulted in the identification of a putative set of metal binding motifs with similarity to that seen in a family of membrane desaturases-hydroxylases. Western analysis using antibodies to an Erg25-GST fusion protein detected two proteins of 34 and 75 kDa. Both proteins are membrane bound and contain one N-glycosyl unit. Immunofluorescence data suggest that the proteins are present in the endoplasmic reticulum and plasma membrane. Although ERG25 transcripts are not iron regulated, there is a large increase in the concentration of transcript in the mutant LT06 grown in low iron medium. These results suggest that the enzyme is regulated not by iron but by an end product of the ergosterol pathway.

Amino Acid Sequence↗