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M Kaufman

Publications and source records attributed to M Kaufman.

At least 37 records · Page 2Linked to original sources

A three-dimensional model of the mouse at embryonic day 9.

This paper describes a digital, three-dimensional model of the mouse embryo at E9. The model was made by reconstruction from images of serial histological sections digitally warped to remove distortions and has a resolution of approximately 9 microns. The model can be digitally resectioned in any plane to provide images which resemble conventional histological sections. The main tissues have been identified and delineated by digital painting so that the anatomical components can be visualized and manipulated in 3-D surface- and volume-rendered views. This provides a three-dimensional definition of anatomy that will provide a useful tool for interpreting and understanding spatial data in mouse embryos. The anatomy of the model is discussed where it provides landmarks for interpretation and navigation or where it is unexpected in light of existing descriptions of the E9 mouse embryo. The complete anatomy is not presented in this paper but will be available on CD-ROM. A detailed description of the technical aspects of the construction of the model is included in an appendix. The model is the first of a series that will form the basis for an atlas/database of mouse development. This reconstruction and its associated anatomy are available in a variety of data formats with some supporting software from http:@genex.hgu.mrc.ac.uk/.

Anatomy, Cross-Sectional↗

Determination of cellular thiol levels in individual viable lymphocytes by means of fluorescence intensity and polarization.

Cellular thiol levels regulate lymphocyte proliferation and death and play a significant role in the immune response. Therefore, the ability to analyze the total protein and non-protein thiol compounds and their distribution among individual living lymphocytes is of great importance. A quantitative measurement of intracellular sulphydryl groups in living lymphocytes using the Cellscan mark F (CS-F) cytometer, in conjunction with the probe CMFDA, is described. This technique permits the detection, identification, and study of sub-populations and single cells in a sample of heterogeneous lymphocytes. The Cellscan apparatus is a laser based scanning cytometer incorporating a unique cell carrier which allows repeated, high-precision measurements of fluorescence intensity (FI) and fluorescence polarization (FP) to be made on intact individual living cells under controlled physiological conditions. The discernible effect of fluorophore molecules bound to thiols having a higher FP than free molecules was used to estimate their relative fractions in living lymphocytes. The results were more conspicuous when the ratio between FP measured at two wavelengths (FPR) of the fluorogenic molecules was used for analysis. In addition, the intracellular dynamic changes in the FI, FP and FPR of the fluorescent probe were also monitored. The cellular sulphydryl content of each lymphocyte within a population was recorded by the CS-F, and sub-populations or individual cells were classified according to their thiol levels and their metabolic rates. Changes in thiol concentration were observed following mitogenic activation of peripheral lymphocytes.

Ethylmaleimide↗

The trace and subgrouping of lymphocyte activation by dynamic fluorescence intensity and polarization measurements.

Cell activation involves conformational changes of cytosolic enzymes, and/or their regulatory proteins, as well as intracellular matrix re-organization. In this work, these changes were monitored by dynamic measurements of fluorescence polarization in single cells incubated with or without phytohaemagglutinin (PHA), using the Cellscan mark S (CS-S) cytometer. This instrument and the procedure used proved to be a powerful tool for distinguishing subpopulations of cells. Grouping of cells by their staining rates (the time rate of change of the fluorescence intensity) yielded three major subgroups. For each subgroup, the fluorescence depolarization (FDP) induced by the incubation with PHA was measured. The kinetics of the subgroups indicate that the major FDP is contributed by the cells with the lowest staining rate. This FDP is approximately 1.5 times greater than that of a bulk population. It is believed that the analysis of kinetic probing might yield an important and more sensitive method for functional marking of subgroups of cells by their response characteristics.

Cell Separation↗

A logical analysis of T cell activation and anergy.

Interaction of the antigen-specific receptor of T lymphocytes with its antigenic ligand can lead either to cell activation or to a state of profound unresponsiveness (anergy). Although subtle changes in the nature of the ligand or of the antigen-presenting cell have been shown to affect the outcome of T cell receptor ligation, the mechanism by which the same receptor can induce alternative cellular responses is not completely understood. A model for explaining both positive (cell proliferation and cytokine production) and negative (anergy induction) signaling of T lymphocytes is described herein. This model relies on the autophosphorylative properties of the tyrosine kinases associated with the T cell receptor. One of its basic assumptions is that the kinase activity of these receptor-associated enzymes remains above background level after ligand removal and is responsible for cellular unresponsiveness. Using a simple Boolean formalism, we show how the timing of the binding and intracellular signal-transduction events can affect the properties of receptor signaling and determine the type of cellular response. The present approach integrates into a common framework a large body of experimental observations and allows specification of conditions leading to cellular activation or to anergy.

Animals↗

Reactivity of peripheral blood lymphocytes to oxidized low-density lipoprotein: a novel system to estimate atherosclerosis employing the Cellscan.

BACKGROUND: The assumption that atherosclerosis involves an autoimmune response to oxidized LDL (oxLDL) is based on the presence of immunocompetent cells and immunoglobulin deposition in the atherosclerotic lesions by successful immunomodulation of the atherosclerotic process and by inhibition of experimental atherosclerosis by antioxidants. The Cellscan system is a multiparameter laser-based static cytometer that enables repeated monitoring of the fluorescence intensity (FI) and polarization (FP) of individual living cells. Analysis of intracellular fluorescein fluorescence polarization (IFFP) has previously been used to define activated lymphocyte population. HYPOTHESIS: In this study, the Cellscan apparatus has been used to monitor cellular response to oxLDL in patients with atherosclerosis and in controls. METHODS: The FI and FP of fluorescein diacetate (FDA)-labeled peripheral lymphocytes were measured following exposure to oxLDL in vitro. Using cluster analysis we were able to identify subpopulations of cells that were characterized by their FI and FP. Forty-two subjects were studied: 22 patients with severe coronary heart disease and 22 control individuals, either healthy or with other diseases. RESULTS: Fluorescence intensity of fluorescein-labeled peripheral blood lymphocytes (PBL) was markedly decreased upon exposure to high doses (> 25 micrograms/ml) of oxLDL concurrently with an increase in FP. A specific and dose-dependent reduction in FP of the high-intensity cell subpopulations, accompanied by higher FI, was evident in patients with ischemic heart disease upon exposure to low doses of oxLDL (up to 25 micrograms/ml). Maximal depolarization was shown upon triggering with 2 micrograms/ml oxLDL. The polarization ratio (the mean polarization value of the specific cell population with and without activation) obtained for patients' lymphocytes was significantly lower (p < 0.01) than that of the control group (0.936 +/- 0.05 and 1.028 +/- 0.055, respectively). CONCLUSION: These data suggest that PBL from patients with active ischemic heart disease show an increased reactivity to oxLDL. A 73% positivity rate was found for ischemic heart disease patients compared with 5% in the control subjects. One of the future prospects of this study might be the advent of a simple and rapid noninvasive test that could assess the extent of atherosclerosis, and possibly even the response to therapy, by monitoring the reactivity of PBL to oxLDL.

Aged↗

A controlled investigation of bodywork in multiple sclerosis.

OBJECTIVE: To determine whether a course of Feldenkrais bodywork would result in significant improvement in physical, mood symptoms and functioning in multiple sclerosis (MS) patients beyond the effects observed using a sham condition (nontherapeutic bodywork). DESIGN: The bodywork method used was the Feldenkrais method. Subjects were randomly assigned to 1 of 2 groups in a crossover design to control for order effects of treatment. Half of the subjects received 8 weeks of sham sessions followed by 8 weeks of Feldenkrais sessions. The other half of the subjects received Feldenkrais sessions first and then sham. All subjects completed the outcome measures prior to the first course of treatment, in between Feldenkrais and sham, and at study completion. SETTING: Participants were recruited from a regional MS clinic and were administered bodywork treatment and outcome measures in a bodywork practitioner's office. SUBJECTS: Twenty individuals with clinically definite MS and disability status scores between 2.0 and 6.0 participated. OUTCOME MEASURES: Nine-hole pegboard test of hand dexterity, Hospital Anxiety and Depression Scale, MS self-efficacy scale, MS Symptom Inventory, MS Performance Scales, and the Perceived Stress Scale. RESULTS: The only significant differences were observed for perceived stress and lowered anxiety after Feldenkrais sessions. There were nonsignificant trends toward higher self-efficacy after both Feldenkrais and sham sessions. MS symptoms, levels of functional ability, and upper extremity performance were not affected by Feldenkrais or sham sessions.

Adult↗

Cervical cancer screening knowledge and practices among Korean-American women.

Cervical cancer is one of the most common cancers of American women. The Papanicolaou (Pap) smear test for cervical screening is a widely used and effective means to reduce the morbidity and mortality rate from cervical cancer through early detection. Despite these benefits, many women have never been screened or are not screened at regular intervals. The purpose of this study was to examine cervical cancer screening knowledge and practices of Korean-American women. The sample consisted of 159 Korean-American women, 40 to 69 years of age. The 1987 Cancer Control Supplement questionnaire was translated into Korean and used to collect data. Twenty-six percent of the respondents never heard of the Pap smear test. Only 34% of respondents reported having had a Pap smear test for screening. The most frequently cited reason for not having had a Pap smear test was absence of disease symptoms. Results indicate that education and usual sources of health care were significant factors related to having heard of or having had a Pap smear test. The findings from this study have important implications for health practitioners and policy makers who serve this ethnic population.

Adult↗

A molar entropy model of age differences in spatial memory.

Two very-short-term-memory, spatial scanning aging experiments were conducted involving a graphics character as a target stimulus. On the probe portion of a trial, the stimulus was presented in the same position as it was on the target portion of the trial (i.e., a same trial) 50% of the time. However, on the remaining 50% of the trials, the probe stimulus was shifted (or transposed) 1, 2, or 3 positions to the right or left of the original presentation (target) position. In Experiment 1, exposure duration was manipulated. In Experiment 2, the number of potential target display positions was manipulated. For both experiments, older adults showed larger transposition distance effects than younger adults for errors. In the past (e.g., P.A. Allen, 1990, 1991), this effect has been attributed to higher levels of internal noise (entropy) in older than younger adults. This research provides converging operations to this contention by using statistical physics methods to rigorously compute the entropy in a molar neural network across age groups. After successfully fitting the statistical mechanics model to the data, the model is proved to have external validity by fitting a simplified version of it to an earlier spatial memory aging experiment reported by P. R. Bruce and J. F. Herman (1986). The results of both traditional reaction time and error rate analyses, as well as the entropy modeling analyses, indicated that older adults exhibited higher levels of entropy than did the younger adults and that this effect appeared to be generalized across processing stage.

Adolescent↗

Midgut bacteria in Anopheles gambiae and An. funestus (Diptera: Culicidae) from Kenya and Mali.

Field studies in Kenya and Mali investigated the prevalence of bacteria in the midguts of malaria vectors, and the potential relationship between gram-negative bacteria species and Plasmodium falciparum sporozoites. Midguts were dissected from 2,430 mosquitoes: 863 Anopheles funestus Giles and 1,037 An. gambiae s.l. Giles from Kenya, and 530 An. gambiae s.l. from Mali. An. funestus had a higher prevalence of gram-negative bacteria (28.5%) compared with An. gambiae collected in Kenya and Mali (15.4 and 12.5%, respectively). Twenty different genera of bacteria were identified by gas chromatography from 73 bacterial isolates from mosquito midguts. Pantoea agglomerans (Enterobacter agglomerans) was the most common species identified. There was no association between gram-negative bacteria in the midgut and P. falciparum sporozoites in field-collected An. gambiae s.l. and An. funestus. However, An. funestus females that harbored gram positive bacteria were more likely to be infected with sporozoites compared with those with no cultivable bacteria or gram negative bacteria in their midguts. Habitat-related variation in the prevalence of diverse types of bacteria in mosquitoes could influence malaria parasite development in mosquitoes and corresponding sporozoite prevalence.

Animals↗

Senile degeneration and cognitive impairment in chronic schizophrenia.

OBJECTIVE: This study was an investigation of the role of Alzheimer-type senile degenerative abnormalities in the cognitive impairment of chronic schizophrenia. METHOD: The study group comprised 145 deceased elderly institutionalized psychiatric patients: 66 with schizophrenia, 26 with mood disorders, 36 with dementia, and 17 with other psychiatric diagnoses. The comparison group included 16 deceased elderly individuals without neurologic or psychiatric disease. Psychiatric diagnoses and cognitive status were established by standardized review of medical records. Neuritic senile plaques and neurofibrillary tangles were identified immunohistochemically and counted, by investigators blind to clinical information, in standardized regions of each brain. RESULTS: Of the subjects with schizophrenia, 68% had definite cognitive impairment, but only 8% satisfied neuropathological criteria for Alzheimer's disease. Among the schizophrenia subjects without Alzheimer's disease, definite cognitive impairment was associated with higher levels of plaques and tangles. The schizophrenia subjects without definite cognitive impairment had fewer plaques and tangles than the unimpaired nonpsychiatric subjects. CONCLUSIONS: Most cases of cognitive impairment in schizophrenia could not be attributed to Alzheimer's disease. An association of mild Alzheimer-type pathology with definite cognitive impairment was unique to schizophrenia. Enhanced sensitivity to the effects of aging on the brain may be a manifestation of diminished cognitive reserve in schizophrenia.

Aged↗

Cytokine evaluation in throat infections.

Inflammatory cytokines have been shown to play an important role in the pathogenesis of various inflammatory processes. In throat infections, intracellular inflammatory cytokines have been detected from the sites of inflammation. The present study aimed to evaluate serum cytokine levels of patients with throat infections and correlate them to the inflammatory parameters and type of inflammation. Significantly higher inflammatory cytokine levels (interleukin [IL]-6 > 7 pg/mL, IL-1 > 1 beta pg/mL, tumor necrosis factor alpha > 1 pg/mL) were detected in most of the patients as opposed to healthy controls. Clinical parameters of infection (fever > 38 degrees C, leukocytosis > 11,000 white blood cells per cubic millimeter, polymorphonuclear neutrophils > 75%) were significantly correlated with high levels of inflammatory cytokines: mainly IL-6 and tumor necrosis factor alpha, and to a lesser degree with IL-1 beta. No correlation, however, was found between the type of inflammation and cytokine levels. The present study indicates a role of inflammatory cytokines in the pathogenesis of throat infections and the need for an anti-inflammatory and anticytokine therapeutic approach.

Adolescent↗

Evaluation of the Periotest as a diagnostic tool for dental implants.

The Periotest is examined as a possible replacement for outdated, inconsistent dental implant stability diagnosis tools. The Periotest has the advantage of offering reproducible findings by measuring the levels of subclinical mobility using an ultrasonically vibrating probe. The Periotest is successful in assessing the stability status of an implant, but it can detect the quantity of bony osseointegration only in terminal cases. Radiography proved to be a more sensitive method of determining pericervical bone loss; therefore, periapical radiographs in addition to the Periotest device were found to offer the most reliable assessment of an implant's status.

Alveolar Bone Loss↗

Transnasal endoscopic management of choanal atresia.

Since 1755, when Roederer first described choanal atresia, more than 350 papers have been published dealing with the various aspects of this entity. Many surgical techniques have been used to treat the malformation, each with its advantages and disadvantages. Endoscopic transnasal repair of choanal atresia provides excellent visualization and enables accurate surgery to be performed on patients of all ages and even on newborn infants. Described are two newborn infants, one with bilateral choanal atresia and the other with bilateral choanal stenosis, successfully treated by endoscopic transnasal repair, with a 12 month follow-up. The technique of endoscopic choanal repair is described, emphasizing it as a highly successful, short and safe procedure with swift recovery and short hospitalization.

Choanal Atresia↗

Presence of herpes simplex DNA in surgical tissue from human epileptic seizure foci detected by polymerase chain reaction: preliminary study.

OBJECTIVES: To determine whether herpes simplex virus causes monofocal epilepsy and to assess the presence of herpes simplex virus 1 (HSV-1) and HSV-2 in surgical specimens from patients with epilepsy by using polymerase chain reaction and Southern blot analysis. BACKGROUND: Herpes simplex virus is a common neurotropic virus capable of latency within the central nervous system; it has a predilection for the temporal lobe. Central nervous system infection with HSV has been associated with seizure activity. DESIGN AND METHODS: Surgical specimens were removed from 50 patients as part of a treatment protocol for monofocal epilepsy. Neuropathological classification was done, and adjacent sections were screened for HSV by using polymerase chain reaction. Tissues obtained post mortem from the temporal lobe cortex of persons with Alzheimer disease (n=17), Parkinson disease (n=14), or nonneurological disease (n=17) served as controls. RESULTS: Twenty (40%) of the 50 epilepsy cases and 2 (4%) of the 48 control cases had at least one sample that tested positive for HSV (P<.001). Sixty-seven percent (8/12) of the epilepsy cases with heterotopia were positive for HSV. CONCLUSIONS: There was a statistically significant difference in the frequency of HSV-positive surgical specimens from monofocal seizure epicenters compared with nonepilepsy control specimens. These data suggest an association of the virus with seizure activity. All specimens positive for HSV (surgical specimens and control specimens) should be examined to determine the activity or latency state of the virus and cellular localization.

Adolescent↗

Tay-Sachs disease and HEXA mutations among Moroccan Jews.

Moroccan Jewry (N>750,000) is the only non-Ashkenazi Jewish community in which Tay-Sachs disease (TSD) is not extremely rare. Previous studies among Moroccan Jewish TSD families identified three HEXA mutations. In this study, extended to enzyme-defined and new obilgate TSD carriers, we found four additional mutations. One of them is a novel, IVS5-2(A-->G) substitution, resulting in exon skipping, and it was found only among enzyme-defined carriers. The seven HEXA identified mutations among Moroccan Jews are: deltaF(304/305), R170Q, IVS-2(A-->G), Y180X, E482K, 1278+TATC, and IVS12+1(G-->C). Their respective distribution among 51 unrelated enzyme-defined and obligate carriers is 22:19:6:1:1:1:1. The mutation(s) remain unknown in only three enzyme-defined carriers. Five of the seven Moroccan mutations, including the three most common ones, were not found among Ashkenazi Jews. Compared with the much larger and relatively homogeneous Ashkenazi population, the finding among Moroccan Jews probably reflects their much longer history.

Heterozygote↗

The mouse atlas and graphical gene-expression database

The large amounts of gene-expression data on mouse development are now too extensive to be stored in any format other than that of a database. Furthermore, as this data is intrinsically graphical and as, in the early developmental stages at least, its boundaries do not map directly to those of anatomical tissues, the natural way to store it is in graphical format. We are therefore constructing a database able to handle such graphical gene-expression data by mapping it onto 3-D reconstructions of mouse embryos whose tissues have been delineated. This article reviews the progress that has been made in this project and describes its two major components, CD-ROMs of the 3-D reconstructions to be held on the user's computer and a gene-expression database that will be maintained at a host site, the two being linked over the internet by a complex Java-based interface for submitting data and querying the database.Copyright 1997 Academic Press Limited Copyright 1997Academic Press Limited

Journal Article↗