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Biomedical subjects

J Kaplan

Publications and source records attributed to J Kaplan.

At least 181 records · Page 10Linked to original sources
PubMed1996

Children's understanding of the meaning and functions of verbal irony.

We investigated children's understanding of irony and sensitivity to irony's meanness and humor. In Study 1, 89 participants (5-6-year-olds, 8-9-year-olds, adults) heard ironic and literal criticisms, and literal compliments. Comprehension of irony emerged between 5 and 6 years of age. Ratings of humor increased with age; ratings of meanness did not (showing that all ages perceived irony as more muted than literal criticism). In Study 2, results from 135 participants (6-7-year-olds, 8-9-year-olds, and adults) replicated these findings and revealed the role of form and intonation. Thus, comprehension of irony emerges between 5 and 6 years of age, and sensitivity to the muting function develops prior to sensitivity to the humor function.

Age Factors↗
PubMed1995

How important is race/ethnicity as an indicator of risk for specific AIDS-defining conditions?

In order to examine differences in the prevalence of AIDS-defining conditions by race/ethnicity, we analyzed U.S. surveillance data for 203,470 adolescents and adults diagnosed with AIDS from 1988 through 1992. A number of AIDS-indicator conditions were more common among certain racial/ethnic groups. The prevalence of extrapulmonary tuberculosis was higher among blacks, Hispanics, Asians/Pacific Islanders, and American Indians/Alaskan Natives than among whites. The prevalence of isosporiasis and toxoplasmosis was higher among Hispanics than among blacks or whites. Furthermore, the likelihood of being diagnosed with extrapulmonary tuberculosis (TB), toxoplasmosis, or isosporiasis was generally higher among foreign-born than among U.S.-born persons of all racial/ethnic groups. The prevalence of all malignancies was higher among whites than among blacks or Hispanics. However, the magnitude of prevalence differences by race/ethnicity was reduced when we controlled for other demographic and exposure risk categories. Although race/ethnicity was significantly associated with the prevalence of a number of conditions, the relative frequency and patterns of AIDS-indicator conditions in different populations are probably most influenced by differences in (1) underlying prevalence or exposure to various etiologic agents causing these conditions, (2) diagnosis and reporting of conditions, and (3) access to care and therapy for HIV-related conditions.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Nocturnal dyspnea and atrial fibrillation predict Cheyne-Stokes respirations in patients with congestive heart failure.

BACKGROUND: Cheyne-Stokes respirations have frequently been noted in highly selected groups of patients with congestive heart failure, but their prevalence in an unselected population with congestive heart failure is undefined. METHODS: One hundred consecutive unselected outpatients or stable inpatients with clinical congestive heart failure encountered by three clinical cardiologists during a 6-month period were screened for Cheyne-Stokes respirations with overnight oximetry. RESULTS: The mean age (+/- SD) of the patients was 70 +/- 8.6 years. Of the 100 patients, 33% had had previous coronary bypass surgery, 77% were men, 57% had hypertension, and 32% had atrial fibrillation. The mean ejection fraction (+/- SD) was 34% +/- 13%. Periodic breathing was assessed qualitatively as Cheyne-Stokes respirations in 27% of patients, nonspecific sleep-disordered breathing (apneas and/or hypopneas) in 43%, and normal in 30%. For patients with Cheyne-Stokes respirations, patients with nonspecific sleep-disordered breathing, and normal subjects, the mean numbers of oxyhemoglobin desaturation events per hour were 24, 10, and 2, and the total numbers of desaturations of 4% or more that lasted less than 3 minutes were 172, 74, and 13. Independent predictors of Cheyne-Stokes respirations vs non-Cheyne-Stokes respirations included a history of nocturnal dyspnea (odds ratio, 4.00; 95% confidence interval, 1.33 to 12.04; P = .01) and atrial fibrillation (odds ratio, 3.24; 95% confidence interval, 1.21 to 8.48; P = .02). CONCLUSIONS: Cheyne-Stokes respirations and nonspecific sleep-disordered breathing are common in unselected patients with congestive heart failure, and Cheyne-Stokes respirations are predicted by a history of nocturnal dyspnea and the presence of atrial fibrillation. Techniques designed to modify the nocturnal breathing pattern of patients with congestive heart failure may be applicable to a large portion of the congestive heart failure population.

Aged↗
PubMed1995

Defective myosin VIIA gene responsible for Usher syndrome type 1B.

Usher syndrome represents the association of a hearing impairment with retinitis pigmentosa and is the most frequent cause of deaf-blindness in humans. It is inherited as an autosomal recessive trait which is clinically and genetically heterogeneous. Some patients show abnormal organization of microtubules in the axoneme of their photoreceptors cells (connecting cilium), nasal ciliar cells and sperm cells, as well as widespread degeneration of the organ of Corti. Usher syndrome type 1 (USH1) is characterized by a profound congenital sensorineural hearing loss, constant vestibular dysfunction and prepubertal onset of retinitis pigmentosa. Of three different genes responsible for USH1. USH1B maps to 11q13.5 (ref. 10) and accounts for about 75% of USH1 patients. The mouse deafness shaker-1 (sh1) mutation has been localized to the homologous murine region. Taking into account the cytoskeletal abnormalities in USH patients, the identification of a gene encoding an unconventional myosin as a candidate for shaker-1 (ref. 14) led us to consider the human homologue as a good candidate for the gene that is defective in USH1B. Here we present evidence that a gene encoding myosin VIIA is responsible for USH1B. Two different premature stop codons, a six-base-pair deletion and two different missense mutations were detected in five unrelated families. In one of these families, the mutations were identified in both alleles. These mutations, which are located at the amino-terminal end of the motor domain of the protein, are likely to result in the absence of a functional protein. Thus USH1B appears as a primary cytoskeletal protein defect. These results implicate the genes encoding other unconventional myosins and their interacting proteins as candidates for other genetic forms of Usher syndrome.

Adult↗
PubMed1995

The FET3 gene product required for high affinity iron transport in yeast is a cell surface ferroxidase.

The yeast FET3 gene is required for high affinity iron transport (Askwith, C., Eide, D., Ho, A. V., Bernard, P. S., Li, L., Davis-Kaplan, S., Sipe, D. M., and Kaplan, J. (1994) Cell 76, 403-410). The gene has extensive sequence homology to the family of multi-copper oxidases. In this communication, we demonstrate that the gene product is a cell surface ferroxidase involved in iron transport. Cells that contain a functional FET3 gene product exhibited an iron-dependent non-mitochondrial increase in oxygen consumption. Comparison of the rate of iron oxidation to O2 consumption yielded an approximate value of 4:1, as predicted for a ferroxidase. Spheroplasts obtained from cells grown under low iron conditions also displayed an iron-dependent increase in O2 consumption. Treatment of spheroplasts with trypsin or affinity-purified antibodies directed against the putative external ferroxidase domain of Fet3 had no effect on basal O2 consumption but inhibited the iron-dependent increase in O2 consumption. Anti-peptide antibodies directed against the cytosolic domain of Fet3 had no effect on O2 consumption. These studies indicate that Fet3 is a plasma membrane ferroxidase required for high affinity iron uptake, in which the ferroxidase-containing domain is localized on the external cell surface.

Amino Acid Sequence↗
PubMed1995

Late motor involvement in cases presenting as "chronic sensory demyelinating polyneuropathy".

Chronic inflammatory demyelinating polyneuropathy (CIDP) is usually characterized by prominent motor deficits. A pure sensory presentation, labeled chronic sensory demyelinating neuropathy (CSDN), has been reported, but it is unclear if this neuropathy is a distinct clinical and immunologic entity or merely the sensory presentation of the more usual sensorimotor CIDP. We describe 5 patients with what initially appeared to be CSDN; 3 subsequently developed substantial weakness coincident with the electrophysiologic appearance of multifocal motor conduction block. These cases indicate that, in some cases, CSDN may be a transitional clinical stage of CIDP in which the more usual sensorimotor deficits develop later. Immune-based therapy, including intravenous immunoglobulin, was found to be effective in both the pure sensory and sensorimotor types.

Chronic Disease↗
PubMed1995

A gene for blepharophimosis-ptosis-epicanthus inversus syndrome maps to chromosome 3q23.

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal dominant malformation of the eyelids that may severely impair visual function. Chromosomal aberrations involving chromosomes 3q23, 3p25 and 7p34 have been reported in BPES but the disease gene has not been hitherto localized by linkage analysis. We have mapped a gene for BPES to chromosome 3q23 in a large French pedigree (Zmax = 4.62 at Theta = 0 for probe AFM 182yc5 at locus D3S1549). The best estimate for the location of the disease gene is at locus D3S1549, between the loci D3S1292 and D3S1555 (maximum lod score of 5.10).

Abnormalities, Multiple↗
PubMed1995

Exclusion of the cone-specific alpha-subunit of the transducin gene in Stargardt's disease.

Stargardt's disease is an autosomal recessive infantile macular degeneration of unknown origin whose gene has been recently mapped to chromosome 1p21-p13 by linkage analysis in eight multiplex families. Since the cone-specific alpha-subunit of the transducin gene (GNAT2) has been mapped to chromosome 1p13, we tested GNAT2 as the disease-causing gene in our series. Using a novel intragenic polymorphism, we show here that GNAT2 is most probably located centromeric to the genetic interval encompassing the disease gene (D1S424-D1S236, location score = 3.54). In addition, single-strand conformation polymorphism and sequence analyses of the eight exons of the GNAT2 gene was performed in our probands. No evidence of a deleterious base substitution was observed in any affected individual. Taken together, these results support the exclusion of GNAT2 as the causal disease gene of Stargardt's disease. come. The pathogenesis is unknown and the treatment is limited to ultraviolet ray protection with dark glasses. Stargardt's disease has been recently mapped to chromosome 1p21-p13 in the genetic interval defined by loci D1S424 and D1S236. In addition, our previous study has suggested that Stargardt's disease is genetically homogeneous (Kaplan et al. 1993). With respect to the physical mapping of the proteins specific to the retinal pigmentary epithelium or to cones we noted that the cone-specific alpha-subunit of the transducin gene (GNAT2) has been mapped to chromosome 1p13 (Wilkie et al. 1992). The human GNAT2 is 9967 bp in length and consists of eight exons with seven introns (Morris and Fong 1993). In the present study, we examined this gene as the candidate gene in eighteen unrelated patients affected with Stargardt's disease.

Base Sequence↗
PubMed1995

"Synchronized" endocytosis and intracellular sorting in alveolar macrophages: the early sorting endosome is a transient organelle.

Incubation of alveolar macrophages in hypoosmotic K(+)-containing buffers results in persistent cell swelling and an inability to undergo regulatory volume decrease. We demonstrate that cells incubated in hypo-K+ show an inhibition of endocytosis without any observed alteration in recycling. The inhibition of endocytosis affected all forms of membrane internalization, receptor and fluid phase. Both increased cell volume and the inhibition of endocytosis could be released upon return of cells to iso-Na+ buffers. The ability to synchronize the endocytic apparatus allowed us to examine hypotheses regarding the origin and maturation of endocytic vesicles. Incubation in hypo-K+ buffers had no effect on the delivery of ligands to degradative compartments or on the return of previously internalized receptors to the cell surface. Thus, membrane recycling and movement of internalized components to lysosomes occurred in the absence of continued membrane influx. We also demonstrate that fluorescent lipids, that had been incorporated into early endosomes, returned to the cell surface upon exposure of cells to hypo-K+ buffers. These results indicate that the early sorting endosome is a transient structure, whose existence depends upon continued membrane internalization. Our data supports the hypothesis that the transfer of material to lysosomes can best be explained by the continuous maturation of endosomes.

Animals↗
PubMed1995

Alterations in immune function following head injury in children.

OBJECTIVE: To investigate cellular and humoral immunity in children immediately after severe head injury and during the early recovery period. DESIGN: Prospective, observational study with factorial design. SETTING: Pediatric ICU of a university teaching hospital. PATIENTS: Fifteen children (median age 9.6 yrs, range 1.7 to 18) with head injury and Glasgow Coma Score of < or = 7. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Skin testing with seven standard antigens was performed and blood samples were obtained for the following measurements: total lymphocyte count and subsets; proliferative response to phytohemagglutinin, concanavalin A, and pokeweed mitogen; and immunoglobulin concentrations on days 1, 7, and 14 and 3 months after injury. The effect of patient plasma on phytohemagglutinin-induced proliferative responses of normal donor lymphocytes was also assessed at these times. Anergy was present in 71% of patients on day 1, 54% of patients on day 7, 31% of patients on day 14, and 18% of patients at 3 months. Total, helper, and suppressor T-cell counts were decreased on day 1, and the T-cell response to phytohemagglutinin was decreased on days 1, 7, and 14 compared with values at 3 months. B-cell counts were increased on day 1, followed by an increase in serum immunoglobulin concentrations 1 to 2 wks later. The B-cell response to pokeweed mitogen was unchanged over the 3-month study period. The phytohemagglutinin responses of normal donor lymphocytes were decreased when incubated with patient plasma obtained on day 7 after injury. CONCLUSIONS: Severe head injury in children is associated with depressed cell-mediated immunity. Plasma immunosuppressive factors may contribute to T-cell dysfunction.

Acute Disease↗
PubMed1995

Sustained production of human transferrin by transduced fibroblasts implanted into athymic mice: a model for somatic gene therapy.

Somatic gene therapy has been proposed as a means of treating inherited diseases involving defective or absent plasma proteins, viral diseases, and cancer. Introduction of the gene of interest into fibroblasts and implantation of these genetically modified fibroblasts using a skin equivalent system may be an attractive model for gene therapy because skin fibroblasts are easily obtained and propagated in culture. This study evaluated expression of the gene for human transferrin (hTf) by genetically modified fibroblasts in vitro and in vivo. NIH 3T3 fibroblasts, which form non-metastasizing tumors in athymic mice, were transduced with a retroviral vector encoding hTf. The transduced cells were cloned by limiting dilution and hTf production by the cloned cells measured. Two clones of cells producing high levels of hTf were used to seed collagen-coated nylon matrices, which were maintained in culture for up to 53 d. The rate of synthesis of hTf by the seeded matrices was constant after 22 d in vitro. Matrices seeded with cloned, transduced cells were implanted subcutaneously into seven athymic mice, and plasma levels of hTf were assessed biweekly. In all animals, the plasma level of hTf was detectable at week 6 after implantation. Levels of hTf remained elevated in the animals until the implants were removed at week 12. At week 10, the level of hTf in the plasma correlated with tumor volume in tumors less than 2000 mm3 in size. The half-life of hTf in the mice was 39.5 h. In this model, gene expression did not decline for the 12-week observation period.

3T3 Cells↗
PubMed1995

No evidence of genetic heterogeneity in dominant optic atrophy.

Autosomal dominant optic atrophy (OPA, MIM 165500) is an eye disease causing a variable reduction of visual acuity with an insidious onset in the first six years of life. It is associated with a central scotoma and an acquired blue-yellow dyschromatopsia. A gene for dominant optic atrophy (OPA1) has recently been mapped to chromosome 3q in three large Danish pedigrees. Here, we confirm the mapping of OPA1 to chromosome 3q28-qter by showing close linkage of the disease locus to three recently reported microsatellite DNA markers in the interval defined by loci D3S1314 and D3S1265 in four French families (Zmax = 5.13 at theta = 0 for probe AFM 308yf1 at locus D3S1601). Multipoint analysis supports the mapping of the disease gene to the genetic interval defined by loci D3S1314 and D3S1265. The present study provides three new markers closely linked to the disease gene for future genetic studies in OPA.

Chromosome Mapping↗
PubMed1995

Unusual association of juvenile macular dystrophy with congenital hypotrichosis: occurrence in two siblings suggesting autosomal recessive inheritance.

A familial association between juvenile macular dystrophy and congenital hypotrichosis is described in two siblings aged 25 and 23 years. We put forward arguments for locating the retinal alteration at the level of the retinal pigment epithelium and suggest that the hair disorder could be a Marie-Unna type hypotrichosis. This association is transmitted as an autosomal recessive condition.

Adult↗
PubMed1995

Prolactin release and clinical response to electroconvulsive therapy in depressed geriatric inpatients: a preliminary report.

Fifteen inpatients (nine women, six men) aged 50-86 years with DSM-IIIR major depression were treated with electroconvulsive therapy (ECT). Electrode placement (unilateral versus bilateral) and total number of treatments were determined by the patients' own psychiatrists according to clinical indications. Prolactin (PRL) was determined after the 1st, 6th, 7th, 9th, 11th, and final ECT treatments. Subjects were rated with the Hamilton Depression Rating Scale (HDRS) at baseline, after the sixth ECT treatment, and upon completion of ECT. PRL response to unilateral ECT was consistent across treatment for each subject. Percentage PRL increase was significantly higher for bilateral than unilateral ECT (alpha = 0.05). Subjects with final HDRS of < 12 tended to have greater peak, increase, and percentage increase PRL at the first unilateral treatment than subjects with final HDRS of at least 12; these trends approached statistical significance (Kruskal-Wallis one-way analysis of variance; peak: p = 0.059, chi = 3.556, df = 1; increase: p = 0.099, chi = 2.722, df = 1; percentage increase: p = 0.099, chi = 2.722, df = 1). Decrease in HDRS after the sixth treatment failed to show a statistically significant relationship to any PRL parameter at the initial unilateral treatment. Further studies are needed to characterize the relationship between PRL response, seizure activity, and stimulus dosing.

Aged↗
PubMed1995

A gene for late-onset fundus flavimaculatus with macular dystrophy maps to chromosome 1p13.

Fundus flavimaculatus with macular dystrophy is an autosomal recessive disease responsible for a progressive loss of visual acuity in adulthood, with pigmentary changes of the macula, perimacular flecks, and atrophy of the retinal pigmentary epithelium. Since this condition shares several clinical features with Stargardt disease, which has been mapped to chromosome 1p21-p13, we tested the disease for linkage to chromosome 1p. We report here the mapping of the disease locus to chromosome 1p13-p21, in the genetic interval defined by loci D1S435 and D1S415, in four multiplex families (maximum lod score 4.79 at recombination fraction 0 for probe AFM217zb2 at locus D1S435). Thus, despite differences in the age at onset, clinical course, and severity, fundus flavimaculatus with macular dystrophy and Stargardt disease are probably allelic disorders. This result supports the view that allelic mutations produce a continuum of macular dystrophies, with onset in early childhood to late adulthood.

Alleles↗
PubMed1994

The mammalian transferrin-independent iron transport system may involve a surface ferrireductase activity.

Mammalian cells accumulate iron from ferric citrate or ferric nitrilotriacetate through the activity of a transferrin-independent iron transport system [Sturrock, Alexander, Lamb, Craven and Kaplan (1990) J. Biol. Chem. 265, 3139-3145]. The uptake system might recognize and transport ferric-anion complexes, or cells may reduce ferric iron at the surface and then transport ferrous iron. To distinguish between these possibilities we exposed cells to either [59Fe]ferric citrate or ferric [14C]citrate and determined whether accumulation of iron was accompanied by the obligatory accumulation of citrate. In HeLa cells and human skin fibroblasts the rate of accumulation of iron was three to five times greater than that of citrate. Incubation of fibroblasts with ferric citrate or ferric ammonium citrate resulted in an enhanced accumulation of iron and citrate; the molar ratio of accumulation approaching unity. A similar rate of citrate accumulation, however, was observed when ferric citrate-incubated cells were exposed to [14C]citrate alone. Further studies demonstrated the independence of iron and citrate accumulation: addition of unlabelled citrate to cells decreased the uptake of labelled citrate without affecting the accumulation of 59Fe; iron uptake was decreased by the addition of ferrous chelators whereas the uptake of citrate was unaffected; reduction of ferric iron by ascorbate increased the uptake of iron but had no effect on the uptake of citrate. When HeLa cells were depleted of calcium, iron uptake decreased, but there was little effect on citrate uptake. These results indicate that transport of iron does not require the obligatory transport of citrate and vice versa. The mammalian transferrin-independent iron transport system appears functionally similar to iron transport systems in both the bacterial and plant kingdoms which require the activities of both a surface reductase and a ferrous metal transporter.

Ascorbic Acid↗
PubMed1994

TGF-beta mediates natural suppressor activity of IL-2-activated lymphocytes.

In addition to generating cells with non-MHC-restricted cytotoxic activity that is characteristic of lymphokine-activated killer (LAK) cells, in vitro cultures of lymphocytes with relatively high concentrations of IL-2 generate cells that simultaneously exhibit two distinct types of suppressor activities: veto, the ability of cells to specifically suppress generation of allo-CTL against their own histocompatibility Ags; and natural suppression, the ability of these same cells to nonspecifically suppress the generation of allo-CTL against both their own and unrelated cell surface Ags. In contrast to veto, which is known to require cell-cell contact between veto-active cells and precursors of CTL, natural suppression is known to be mediated by soluble factors. To identify and characterize suppressor factors that might mediate the natural suppressor activity of IL-2-activated lymphocytes, murine spleen cells were cultured with 1000 U/ml IL-2, and, after varying periods of incubation, their LAK cytolytic activity and natural suppressor activity was determined and cell supernatants were collected and tested for their effects on mixed lymphocyte culture-induced generation of allo-CTL. Like the IL-2-activated lymphocytes themselves, supernatants of these cells nonspecifically inhibited mixed lymphocyte culture-induced generation of allo-CTL. Rabbit anti-TGF-beta specifically neutralized the suppressive effects of both LAK cell supernatants and the IL-2-activated lymphocytes themselves. These findings indicate that TGF-beta is the primary mediator of the natural suppressor activity of IL-2-activated lymphocytes.

Animals↗