Search PubMed⌕ Search

Biomedical subjects

M Mendelsohn

Publications and source records attributed to M Mendelsohn.

At least 19 recordsLinked to original sources
PubMed1999

Social perspective taking and use of discounting in children's perceptions of others' helping behavior.

The authors investigated the relationship between children's ability to take the social perspective of another and their use of the causal attribution principle known as discounting in assessing others' kindness in helping. The participants (N = 153), 7 to 16 years old, were interviewed in a township bordering Johannesburg. Each participant was administered 2 perspective-taking tasks and a series of vignettes, based on prosocial versus self-interested motives, assessing perceptions of kindness in helping. A significant relationship was established at p < .01 between social perspective-taking ability and use of discounting, such that participants at higher perspective-taking levels judged helpful behavior as significantly less kind than did their peers when the behavior was motivated by self-interest. This finding is interpreted in terms of literature suggesting that advances in perspective taking facilitate the recognition of the manipulative function of externally offered incentives. Observations are made regarding the cross-cultural investigation of these variables.

Altruism↗
PubMed1998

Serotonin receptor 1A knockout: an animal model of anxiety-related disorder.

To investigate the contribution of individual serotonin (5-hydroxytryptamine; 5-HT) receptors to mood control, we have used homologous recombination to generate mice lacking specific serotonergic receptor subtypes. In the present report, we demonstrate that mice without 5-HT1A receptors display decreased exploratory activity and increased fear of aversive environments (open or elevated spaces). 5-HT1A knockout mice also exhibited a decreased immobility in the forced swim test, an effect commonly associated with antidepressant treatment. Although 5-HT1A receptors are involved in controlling the activity of serotonergic neurons, 5-HT1A knockout mice had normal levels of 5-HT and 5-hydroxyindoleacetic acid, possibly because of an up-regulation of 5-HT1B autoreceptors. Heterozygote 5-HT1A mutants expressed approximately one-half of wild-type receptor density and displayed intermediate phenotypes in most behavioral tests. These results demonstrate that 5-HT1A receptors are involved in the modulation of exploratory and fear-related behaviors and suggest that reductions in 5-HT1A receptor density due to genetic defects or environmental stressors might result in heightened anxiety.

Animals↗
PubMed1998

Neuronal patterning by BMPs: a requirement for GDF7 in the generation of a discrete class of commissural interneurons in the mouse spinal cord.

Inductive factors are known to direct the regional differentiation of the vertebrate central nervous system (CNS) but their role in the specification of individual neuronal cell types is less clear. We have examined the function of GDF7, a BMP family member expressed selectively by roof plate cells, in the generation of neuronal cell types in the dorsal spinal cord. We find that GDF7 can promote the differentiation in vitro of two dorsal sensory interneuron classes, D1A and D1B neurons. In Gdf7-null mutant embryos, the generation of D1A neurons is eliminated but D1B neurons and other identified dorsal interneurons are unaffected. These findings show that GDF7 is an inductive signal from the roof plate required for the specification of neuronal identity in the dorsal spinal cord and that GDF7 and other BMP family members expressed by the roof plate have non-redundant functions in vivo. More generally, these results suggest that BMP signaling may have a prominent role in the assignment of neuronal identity within the mammalian CNS.

Amino Acid Sequence↗
PubMed1998

Odorant receptors govern the formation of a precise topographic map.

Olfactory neurons expressing a given odorant receptor project with precision to 2 of the 1800 glomeruli within the olfactory bulb to create a topographic map of odor quality. We demonstrate that deletions or nonsense mutations in the P2 odorant receptor gene cause the axons of these cells to wander rather than converge on a specific glomerulus. Receptor substitution experiments that replace the P2 gene with the coding region of the P3 gene result in the projection of P3-->P2 axons to a glomerulus touching the wild-type P3 glomerulus. These data, along with additional receptor substitutions, indicate that the odorant receptor plays an instructive role in the establishment of the topographic map.

Animals↗
PubMed1998

External beam radiation therapy for choroidal neovascularization.

OBJECTIVE: This study aimed to determine the effect of external beam radiation therapy on choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN: The study design was a nonrandomized clinical trial with an historic control group. PARTICIPANTS: A total of 91 patients were treated with external beam radiation. These patients were compared retrospectively to the 119 patients in a control group. INTERVENTION: Patients with subfoveal CNV who did not meet the criteria for laser treatment defined by published reports from the Macular Photocoagulation Study Group or who did not want laser treatment were considered for radiation therapy in a nonrandomized, prospective clinical trial. Additional entry criteria for this prospective study included visual acuity better than or equal to 20/320 on the Early Treatment Diabetic Retinopathy Study chart and a lesion size less than 12 disc areas. The patients were treated with 5 fractions of 200 cGy 6 MV external beam photons. MAIN OUTCOME MEASURES: The visual acuity measured at baseline was compared to the visual acuity after 1 year of follow-up. RESULTS: The mean baseline visual acuity of the 91 patients entered into the Radiation Study was 20/80. After 1 year, 83 patients (91.2%) completed follow-up, and their mean visual acuity dropped to 20/200. By comparison, the mean baseline visual acuity of the control patients also was 20/80, and after 1 year, the control subjects had a mean visual acuity of 20/125. At 1 year of follow-up, 49.4% of patients treated with radiation and 38.1% of the control subjects lost 3 or more lines of visual acuity (P = 0.16). CONCLUSIONS: This study found that external beam radiation using 1000 cGy in 5 fractions, a dose similar to that used in previous studies, was not effective in the treatment of CNV secondary to AMD. These results suggest that patients should not be treated with this dose of external beam radiation for CNV secondary to AMD.

Aged↗
PubMed1998

Gore-tex augmentation grafting in rhinoplasty--is it safe?

OBJECTIVE: The utility of the Gore-tex soft-tissue patch in vascular and hernia surgery over the last 20 years led to its application in facial augmentation and rhinoplasty over the last decade. The early success of initial reported series must be balanced against the long-term problems that have faced all implant materials used in the nose in the past. Gore-tex is attractive to the facial plastic surgeon because of its ease in handling and sculpting, and its plentiful supply. This review analyzes the results of Gore-tex augmentation grafting. METHODS AND RESULTS: In a personal series of 30 rhinoplasty cases with minimum 18 month follow-up, there were three cases of infection, two of which required Gore-tex removal, and one seroma requiring Gore-tax removal. In two other patients, the Gore-tex was associated with excessive scar tissue. CONCLUSION: Our results led to the development of guidelines for Gore-tex usage in the nose. Since adopting these guidelines, the authors have not yet experienced any complications with Gore-tex.

Adolescent↗
PubMed1997

Enhanced neuronal death from focal ischemia in AMPA-receptor transgenic mice.

Excitatory amino acid (EAA) receptors play an important role in neuronal cell death in acute cerebral ischemia. Blocking the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) subtype of EAA receptor has been shown to reduce cell death in global cerebral ischemia. However their role in focal stroke, although suggestive, has remained more contentious. To clarify this issue, we generated transgenic mice overexpressing the AMPA receptor (AMPAR) subunit GluR2-flip which would increase AMPAR-mediated currents. Excitatory neurons in these transgenic mice are thus predicted to be more susceptible than wild-type neurons to EAA (glutamate)-induced excitotoxic damage. Consistent with this prediction, cultured neurons from transgenic mice had a lower LD50 for exposure to glutamate (10(-3)-10(-5) M for 5 min) compared to wild-type neurons. Moreover, transgenic mice subjected to permanent focal ischemia of the middle cerebral artery (MCA) using the intralumenal filament model sustained larger infarctions compared to wild-type controls. Hence we have developed a genetic mouse model that demonstrates the crucial role of AMPAR containing GluR2-flip in the pathogenesis of focal hypoxic-ischemic neuronal cell death. This model will be a valuable tool in elucidating molecular mechanisms of glutamate excitotoxicity and evaluating the efficacy of glutamate receptor antagonists in attenuating post-ischemic neuronal cell death.

Alternative Splicing↗
PubMed1997

Nuclear factor interleukin 6 motifs mediate tissue-specific gene transcription in hypoxia.

Activation of transcription at the nuclear factor interleukin 6 (NF-IL-6) DNA binding motif modulates expression of multiple genes important in host adaptive and developmental mechanisms. Studies showing that hypoxia-induced transcription of IL-6 in cultured endothelial cells was due to transcriptional activation by the NF-IL-6 motif in the promoter (Yan, S.-F., Tritto, I., Pinsky, D., Liao, H., Huang, J., Fuller, G., Brett, J., May, L., and Stern, D. (1995) J. Biol. Chem. 270, 11463-11471) led us to prepare transgenic mice using 115- or 14-base pair regions of the promoter encompassing the NF-IL-6 site ligated to the lacZ reporter gene and the basal thymidine kinase promoter. On exposure to hypoxia or induction of ischemia, mice bearing either of the constructs showed prominent expression of the transgene in lung and cardiac vasculature and in the kidney but not in the liver (parenchyma or vasculature). In contrast, transgenic mice bearing a mutationally inactivated NF-IL-6 site showed no increase in transgene expression in hypoxia. Gel retardation assays revealed time-dependent, hypoxia-enhanced nuclear binding activity for the NF-IL-6 site in nuclear extracts of the heart, lung, and kidney but not in the liver; the hypoxia-enhanced band disappeared on addition of antibody to C/EBPbeta-NF-IL-6. Consistent with the specificity of hypoxia-mediated activation of C/EBPbeta-NF-IL-6, gel retardation assays showed no change in the intensity of the hypoxia-enhanced gel shift band in the presence of excess unlabeled oligonucleotide probes or antibodies related to other transcription factors, including NFkappaB, AP1, cAMP response element-binding protein, SP1, and hypoxia-inducible factor 1. These data indicate that the transcription factor NF-IL-6 is sensitive to environmental oxygen deprivation, and the tissue-specific pattern of gene expression suggests that local mechanisms have an important regulatory effect.

Animals↗
PubMed1996

Visualizing an olfactory sensory map.

We have developed a genetic approach to visualize axons from olfactory sensory neurons expressing a given odorant receptor, as they project to the olfactory bulb. Neurons expressing a specific receptor project to only two topographically fixed loci among the 1800 glomeruli in the mouse olfactory bulb. Our data provide direct support for a model in which a topographic map of receptor activation encodes odor quality in the olfactory bulb. Receptor swap experiments suggest that the olfactory receptor plays an instructive role in the guidance process but cannot be the sole determinant in the establishment of this map. This genetic approach may be more broadly applied to visualize the development and plasticity of projections in the mammalian nervous system.

Animals↗
PubMed1996

Transgenes encoding both type I and type IV c-abl proteins rescue the lethality of c-abl mutant mice.

Mice carrying homozygous mutations in the c-abl gene (abl-(m1) or abl2) exhibit severe, though variable phenotypes, including a high rate of postnatal mortality, runting, morphological abnormalities, a susceptibility to infections, and selected immune system defects. To further determine the role of the c-Abl protein in vivo, we have generated three lines of mice expressing c-abl transgenes. These minigenes encode the two major forms of the c-abl gene product (c-Abl types I and IV) and a kinase defective type IV c-Abl. The transgenic lines, in Abl-positive genetic backgrounds, were phenotypically almost indistinguishable from their non-transgene littermates and expressed the c-abl transgene in a variety of tissues at levels comparable to that of the endogenous c-abl gene. When the transgenes were introduced into a mutant c-abl strain by mating, the mutant c-abl phenotype was almost completely rescued by either of the c-abl type I or type IV transgenes, but not by the kinase-defective transgene. These findings suggest that either of the two alternatively spliced c-abl gene products can provide the in vivo functions of c-Abl, and that these functions are dependent on kinase activity.

Animals↗
PubMed1996

Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation.

Motor neuron differentiation is accompanied by the expression of a LIM homeodomain transcription factor, Islet1 (ISL1). To assess the involvement of ISL1 in the generation of motor neurons, we analyzed cell differentiation in the neural tube of embryos in which ISL1 expression has been eliminated by gene targeting. Motor neurons are not generated without ISL1, although many other aspects of cell differentiation in the neural tube occur normally. A population of interneurons that express Engrailed1 (EN1), however, also fails to differentiate in Isl1 mutant embryos. The differentiation of EN1+ interneurons can be induced in both wild-type and mutant neural tissue by regions of the neural tube that contain motor neurons. These results show that ISL1 is required for the generation of motor neurons and suggest that motor neuron generation is required for the subsequent differentiation of certain interneurons.

Animals↗
PubMed1996

Season of birth and schizophrenia: southern hemisphere data.

OBJECTIVE: The association between winter birth and increased incidence of schizophrenia is well documented in the northern hemisphere. The present study examined season of birth and schizophrenia in a southern hemisphere population from a mild temperate climate. METHOD: The seasonal incidence of birth in schizophrenic patients was compared, using Chi-squared tests, to normative population birth rates. RESULTS: A statistically significant seasonal pattern, with a peak in late spring and early summer, was obtained. CONCLUSION: This supports northern hemisphere findings regarding calendar month, but not season, of excess schizophrenic births. This has implications for viral and other aetiological hypotheses dependent on meteorological factors.

Birth Rate↗
PubMed1996

Violent political contexts and the emotional concerns of township youth.

This article presents the findings of a series of studies that examine the perceptions of black South African youth about township life and the civil conflict and violence it encompasses. The studies were conducted with comparable samples of 58-82 youth at 3 points in South Africa's history, all characterized by high levels of violence but differing in terms of their political contexts. These contexts were overt State-community conflict, covert opposition and political repression, and intracommunity violence. The data revealed that in all 3 contexts youth reported a high exposure to violence, but only when violence occurred in the context of intracommunity conflict was it subjectively construed to be the most problematic. Reasons for this may include the real increase in more extreme forms of violence, including deaths, that occurs in intracommunity violence and the blurring of the distinction between political and criminal violence in this context.

Adaptation, Psychological↗
PubMed1995

Role of gastroesophageal reflux disease in patients with cervical symptoms.

Otolaryngologists commonly see patients with various nonspecific upper aerodigestive or "cervical" symptoms. The relationship between gastroesophageal reflux disease and these symptoms has been studied but remains unclear. We reviewed the records of 216 patients with various cervical symptoms. Each patient underwent a uniform investigation that included barium swallow, esophageal manometry, acid stimulation testing, and esophagoscopy with distal biopsy. Patients were treated with a combination of a histamine H2 blocker or omeprazole and a prokinetic agent. Follow-up was obtained in 194 patients. Overall, evidence of gastroesophageal reflux disease was detected in 73% of patients. Complete resolution or improvement of symptoms was seen in 84% of patients with treatment. We believe gastroesophageal reflux disease is an important factor in the cause of cervical problems.

Adolescent↗
PubMed1995

The aesthetic nose: do we agree?

The surgeon and patient use the preoperative consultations to develop an agreement regarding the aesthetic goals of a rhinoplasty. This study was designed to evaluate whether people do agree on what makes a nose attractive. Computerized video-imaging technology was used to create nine case studies. The graphics software permitted precise modification to either tip projection, tip rotation, or size of the dorsal hump. Only one parameter was altered in each case. Two hundred fifty judges were asked to identify the most attractive image in each case study. Significant trends were observed in each case, but every image received the preference of some judges. Most judges preferred midrange values in eight of nine cases, but overrotation of the tip was preferred to tip droop, overremoval of the dorsal hump was preferred to underremoval, and overprojection of the tip was preferred to underprojection. The discrepancy in what constitutes an aesthetic nose reinforces the need for the surgeon to clearly understand the patient's specific requests rather than to aim to produce a "standard nose.".

Humans↗
PubMed1994

Sp1 elements protect a CpG island from de novo methylation.

Animal somatic cell DNA is characterized by a bimodal pattern of methylation: tissue-specific genes are methylated in most cell types whereas housekeeping genes have 5' CpG islands which are constitutively unmethylated. Because methyl moieties derived from the gametes are erased in the morula and early blastula, this profile must be re-established in every generation; this is apparently accomplished by a wave of non-CpG island de novo methylation that occurs at implantation. Using transfection into embryonic stem cells and transgenic mice as a model system, we now show that Sp1 elements play a key role in protecting a CpG island in the adenine phosphoribosyltransferase (APRT) gene from de novo methylation. This recognition mechanism represents a critical step in embryogenesis, as it is responsible for setting up the correct genome methylation pattern which, in turn, is involved in regulating basal gene expression in the organism.

Adenine Phosphoribosyltransferase↗
PubMed1994

Differential activation of transcription versus recombination of transgenic T cell receptor beta variable region gene segments in B and T lineage cells.

We have tested the ability of the T cell receptor beta (TCR-beta) transcriptional enhancer (E beta) to confer transcriptional activation and tissue-specific V(D)J recombination of TCR-beta V, D, and J segments in a transgenic minilocus recombination substrate. We find that the minimal E beta element, as previously shown for a DNA segment that contained the E mu element, promotes a high level of substrate D to J beta rearrangement in both B and T cells, but only promotes V beta to DJ beta rearrangement in T cells. Thus, both the E mu and E beta elements similarly direct V(D)J recombination of this substrate in vivo, supporting a general role for transcriptional enhancers in the normal regulation of this rearrangement process. Surprisingly, however, we found that both the V beta and DJ beta portion of the constructs were transcribed in an enhancer-dependent fashion (conferred by either E mu or E beta) in both B and T lineage cells, including normal precursor B cells propagated in culture. These findings indicate that, at least in some contexts, transcriptional activation, per se, is not sufficient to confer V(D)J recombinational accessibility to a substrate V gene segment.

Animals↗