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Biomedical subjects

D Cohen

Publications and source records attributed to D Cohen.

At least 469 records · Page 26Linked to original sources

MEG versus EEG localization test using implanted sources in the human brain.

It is believed that the magnetoencephalogram (MEG) localizes an electrical source in the brain to within several millimeters and is therefore more accurate than electroencephalogram (EEG) localization, reported as 20 mm. To test this belief, the localization accuracy of the MEG and EEG were directly compared. The signal source was a dipole at a known location in the brain; this was made by passing a weak current pulse simulating a neural signal through depth electrodes already implanted in patients for seizure monitoring. First, MEGs and EEGs from this dipole were measured at 16 places on the head. Then, computations were performed on the MEG and EEG data separately to determine the apparent MEG and EEG source locations. Finally, these were compared with the actual source location to determine the MEG and EEG localization errors. Measurements were made of four dipoles in each of three patients. After MEGs with weak signals were discounted, the MEG average error of localization was found to be 8 mm, which was worse than expected. The average EEG error was 10 mm, which was better than expected. These results suggest that the MEG offers no significant advantage over the EEG in localizing a focal source. However, this does not diminish other uses of the MEG.

Adult↗

Heterogeneity of HLA genetic factors in IDDM susceptibility.

The association of certain HLA-D alleles with insulin-dependent diabetes mellitus (IDDM) is well known. One hundred and sixty-one non-related diabetic individuals and 142 non-related healthy controls were typed for the HLA DR-DQw-Dw association, using a restriction fragment length polymorphism (RFLP) typing method that combines three probe/enzyme systems: DRB/Taq I, DQB/Taq I, and DQB/Bam HI. Comparison of frequencies in both diabetics and controls confirms previous results in terms of HLA class II and IDDM association. Moreover, we have found that DR3/3 heterozygous individuals are more susceptible to IDDM when they are also Dw25 (associated with B18) than when they are Dw24 (associated with B8). Using oligonucleotide dot-blot hybridizations we analyzed the HLA-DQB1 sequence of DR3,Dw24 and DR3,Dw25 homozygous individuals, and we found no difference at position 57 between these two DR3-carrying haplotypes. This observation points to the heterogeneity of HLA genetic factors in IDDM susceptibility.

Alleles↗

Intellectual, academic, and adaptive functioning of Tourette syndrome children with and without attention deficit disorder.

The intellectual, academic, and adaptive strengths and weaknesses of 30, medication-free children (M = 10.5 years) with Tourette syndrome (TS) were assessed with a battery of standardized psychoeducational measures and the Vineland Adaptive Behavior Scales. Results indicated significant relative weaknesses in mental and written arithmetic, and relative strengths in reading achievement and abstract, logical thinking. Socialization skills emerged as a significant weakness in adaptive functioning. Comparisons between TS children with attention deficit disorder with hyperactivity (ADD-H) (n = 19) weakness in both groups in all areas assessed, but significantly lower performance IQs in TS subjects with ADD-H. These findings are discussed in relation to future research with TS children.

Achievement↗

Effect of androgenic gland ablation on morphotypic differentiation and sexual characteristics of male freshwater prawns, Macrobrachium rosenbergii.

Mature males of the freshwater prawn, Macrobrachium rosenbergii (de Man), may change from one to another morphotype, according to a set sequence. Small males may develop into orange-claw males and orange-claw males into dominant blue-claw males. Each of the three morphotypes demonstrates distinctive reproductive behavior and secondary sexual characteristics. The role of the androgenic gland in this morphotypic transformation was examined experimentally by bilateral androgenic gland ablation (andrectomy) of small males and orange-claw males. For andrectomy initiated in the small male morphotype, transformation to the next morphotype was permitted (orange-claw), but subsequent transformation to the blue-claw morphotype was blocked. Andrectomy of orange-claw males did not prevent transformation into the blue-claw. Andrectomy on both small and orange-claw males caused disappearance of the genital papillae and atrophy of the sperm ducts and testes. The growth rates of the andrectomized small and orange-claw males were significantly lower than those of the unoperated and sham-operated controls. We conclude that androgenic gland factors control not only the differentiation of male secondary sexual characteristics but also morphotypic differentiation. Bioassays based on the results of this study will be instrumental in the characterization of such a factor(s).

Animals↗

The products of the mdr1a and mdr1b genes from multidrug resistant murine cells have similar degradation rates.

Two vinblastine-resistant sublines of the murine macrophage-like cell line J774.2, J7.V1-1 and J7.V3-1, overproduce unique forms of P-glycoprotein that are encoded by distinct mdr genes, mdr1b and mdr1a, respectively. Degradation rates of the two P-glycoprotein isoforms were measured by immunoprecipitation of P-glycoprotein. The half-life of immunoprecipitable P-glycoprotein from J7.V1-1 cells was 16.8 +/- 0.5 hours and from J7.V3-1 cells, 17.4 +/- 0.5 hours. This rate was not influenced by the presence of vinblastine in the growth medium. The data indicate that P-glycoproteins derived from distinct genes have similar degradation rates.

Animals↗

Nucleotide sequence of the HLA-A26 class I gene: identification of specific residues and molecular mapping of public HLA class I epitopes.

A cosmid clone bearing an HLA class I gene has been isolated from a human genomic library by hybridization to a class I-specific probe. This clone encodes the HLA-A26 molecule characterized by immunologic reagents on murine transfected L cells. Nucleotide sequencing of the A26 allele has been performed, and the deduced amino acid sequence was compared with previously published HLA class I sequences. Amino acid sequence homologies between HLA-A26 molecules and members of the HLA-AW19 cross-reactive group were observed and allowed us to demonstrate that residue Q144 is the only critical residue involved in the binding of the 4E monoclonal antibody defining an epitope common to all HLA-B, -C, and -Aw19 alleles. This study also permitted designation of a V residue at position 189 in the third domain as possibly involved in the binding of the B1-23-2 monoclonal antibody. Furthermore, we located clusters of variability in reference to the three-dimensional structure of the HLA-A molecules, i.e., the ninth residue of the first beta-strand domain, the upper surface of the first helical region, and both beta and alpha structures of the alpha 2 domain.

Amino Acid Sequence↗

Construction and characterization of a yeast artificial chromosome library containing seven haploid human genome equivalents.

Prior to constructing a library of yeast artificial chromosomes (YACs) containing very large human DNA fragments, we performed a series of preliminary experiments aimed at developing a suitable protocol. We found an inverse relationship between YAC insert size and transformation efficiency. Evidence of occasional rearrangement within YAC inserts was found resulting in clonally stable internal deletions or clonally unstable size variations. A protocol was developed for preparative electrophoretic enrichment of high molecular mass human DNA fragments from partial restriction digests and ligation with the YAC vector in agarose. A YAC library has been constructed from large fragments of DNA from an Epstein-Barr virus-transformed human lymphoblastoid cell line. The library presently contains 50,000 clones, 95% of which are greater than 250 kilobase pairs in size. The mean YAC size of the library, calculated from 132 randomly isolated clones, is 430 kilobase pairs. The library thus contains the equivalent of approximately seven haploid human genomes.

Cloning, Molecular↗

Response to trivalent oral poliovirus vaccine with and without immune serum globulin in young adults in Israel in 1988.

Fifteen cases of type 1 paralytic poliomyelitis occurred in August 1988, mainly among young adults in the Jewish population of Israel, where vaccine coverage exceeds 90%. The military forces, as a precaution against further spread of the virus, vaccinated all recruits in late September. They received oral poliovirus vaccine (OPV) simultaneously with prophylactic immune serum globulin (ISG) to protect against hepatitis A virus infection. Since it is generally not recommended to administer live vaccines simultaneously with ISG, the serologic response to OPV given at the same time as ISG was compared with the response when OPV was given alone; specimens were also available from a control group receiving ISG alone. No effect of ISG on the antibody response to OPV was found, and thus there appears to be no contraindication to giving OPV at the same time as injecting pooled ISG--particularly relevant for travelers to areas endemic for both diseases, who have to leave at short notice. Of recruits 18-19 years of age, 21% lacked antibodies to type 1 poliovirus, suggesting either a decline in antibody titers with age or a lack of vaccine potency during earlier years. After the booster, only 2% lacked type 1 antibody, and the geometric mean titer increased from 1:16 to 1:698.

Adult↗

Improved results using OKT3 as induction immunosuppression in renal allograft recipients with delayed graft function.

Delayed graft function remains a major problem in cadaveric renal allograft transplantation. We have used 2 different immunosuppressive induction regimens in patients with delayed graft function. The first regimen, used in 40 patients from January 1985 to December 1986, consisted of CsA (8 mg/kg/day, orally within 48 hr of cadaveric renal transplantation regardless of graft function), azathioprine (1.5-2.5 mg/kg/day), and steroids (methylprednisolone 375 mg on day 0, then prednisone tapered to 30 mg/day by day 10 with slow tapering to 7.5-10 mg/day over the first 6 months after transplantation). A second regimen, used from January 1987 to March 1989, employed the same doses of azathioprine and steroids; however, OKT3 (5 mg i.v./day for 7-21 days) was administered in the 34 patients who had delayed graft function. CsA was withheld until ATN resolved. The use of OKT3 as induction immunosuppression in patients with ATN led to a significant increase in 1-year graft survival (80% vs. 55%) while markedly decreasing the incidence of rejection episodes (44% vs. 82%) and the duration of nonfunction (9.4 vs. 14.9 days). There were 5 CMV infections in patients treated with OKT3. Antibodies to OKT3 developed in only 1 of 34 patients treated with OKT3. Five of 7 patients who received a second course of OKT3 successfully reversed the rejection episode. Patient survival (89%) was the same in the 2 groups. The benefit of OKT3 on long-term graft survival appears to stem from elimination of early rejection episodes that may be difficult to diagnose in a poorly functioning allograft. We conclude that OKT3 induction provides superior results over CsA induction at doses given in renal allograft recipients with delayed graft function without a significant increase in morbidity or mortality and permits the reuse of OKT3 for treatment of rejection in most cases.

Antibodies, Anti-Idiotypic↗

Structural analysis of the mouse mdr1a (P-glycoprotein) promoter reveals the basis for differential transcript heterogeneity in multidrug-resistant J774.2 cells.

In multidrug-resistant mouse J774.2 cells, the differential overproduction of functionally distinct phosphoglycoprotein isoforms reflects the amplification or transcriptional activation or both of two mdr gene family members, mdr1a and mdr1b. The mdr1a gene is a complex transcriptional unit whose expression is associated with multiple transcript sizes. Independently selected multidrug-resistant J774.2 cell lines differentially overexpress either 4.6- and 5.0-kilobase (kb) or 4.7- and 5.1-kb mdr1a transcripts. However, abundant overproduction of the mdr1a gene product was observed only in cell lines which overexpressed the 4.6- and 5.0-kb mRNAs. In order to determine the basis for mdr1a transcript heterogeneity and the relationship between transcript size and steady-state mdr1a protein levels, genomic and cDNA sequence analyses of the 5' and 3' ends of the mdr1a gene were carried out. Promoter sequence analysis and primer extension mapping indicated that mdr1a transcripts were differentially initiated from two putative promoters to generate either 5.1- and 4.7-kb or 5.0- and 4.6-kb transcripts in four multidrug-resistant J774.2 cell lines. Sequence analysis of 3' cDNA variants and a 3' genomic fragment revealed that the 5.1- and 5.0-kb mRNAs had identical 3'-untranslated regions which differed from those of the 4.7- and 4.6-kb mRNAs as a result of the utilization of a more downstream alternative poly(A) addition signal. Transcript initiation from the putative upstream promoter correlated with a 70 to 85% decrease in steady-state mdr1a protein levels relative to transcript levels. In addition, the identification of putative AP-1 and AP-2 promoter elements suggests a possible role for protein kinase A and protein kinase C in the regulation of mdr1a. The implications of these findings for mdr gene expression and regulation are discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Induction of suppressor cell activity by cyclosporin A and/or uremic serum in normal versus uremic peripheral blood mononuclear cells.

We investigated induction of suppressor cell activity in peripheral blood mononuclear cells (PBMC) from normal or uremic subjects. The cells were primed with cyclosporin A (CS-A), uremic serum, or both and subsequently cocultured with fresh phytohemagglutinin-stimulated normal allogeneic responders. CS-A-primed normal as well as uremic PBMC significantly suppressed responder cell thymidine incorporation. Uremic serum primed normal, but not the uremic, PBMC exerted a significant suppression on responder cell proliferation. No significant additive suppressive effect was detected following coculture of responders with PBMC primed by CS-A and uremic serum together. Exclusion of a distinct suppressor cell subset by panning, using anti-Leu-2b monoclonal antibody, did not result in blunting suppressive activity of the CS-A or uremic serum pretreated cells. On the other hand, adherent cell depletion of primed PBMC completely abolished their subsequent suppressive effect on responder cell proliferation.

Adult↗

Neutron and gamma-irradiation of bacteriophage M13 DNA: use of standard neutron irradiation facility (SNIF).

We describe here the use of the Van de Graaff accelerator as a source of high energy neutrons for biological irradiation. Single-stranded bacteriophage M13 DNA was chosen as the system to determine the relative biological effectiveness of monoenergetic neutrons. A Standard Neutron Irradiation Facility (SNIF) was established using a 3 MV Van de Graaff accelerator. The 2D (d,n)3He nuclear reaction was used to produce neutron fluxes of 3 x 10(8) cm 2 sec-1 yielding dose rates as high as 50 Gy h-1. A detailed description of the neutron source, neutron fluence measurement, dose calculation and calibration are included. Exposure of single-stranded bacteriophage M13 DNA to 90 Gy of neutrons reduced survival to 0.18% of the unirradiated value. 500 Gy of gamma-rays were required for the same level of killing, and RBE was estimated at 6 based on Do values. Determination of the extent of DNA damage after exposure to cleavage using gel electrophoresis, gave RBE values of 6-8 which was very similar to that observed for bacteriophage survival. The facility described here provides a reproducible source of high energy monoenergetic neutrons and dose levels suitable for experiments designed to measure DNA damage and effects on DNA synthesis.

Coliphages↗

Sociodemographic correlates of neutralizing poliovirus and hepatitis A virus antibodies as markers of different modes of acquiring immunity.

The prevalence and sociodemographic correlates of antibodies against poliovirus and hepatitis A virus (HAV) were compared in a random sample of 457 military recruits in Israel inducted during 1987. Lower socioeconomic status (SES) was associated with a higher prevalence of anti-HAV antibodies (67.3 vs 32.5 percent), whereas the reverse was true for type 1 poliovirus (78.4 vs 89.5 percent). While the high prevalence of anti-HAV antibodies observed in the lower SES groups reflects considerable natural exposure to enteroviruses, immunity against poliovirus appears to be determined primarily by compliance with vaccination.

Antibodies, Viral↗

The new old market: trends in hospital services for the aged.

Hospital health care services for the rapidly aging population should continue to expand. Several recent trends include the following: The overall number and proportion of admissions for the aged have increased since 1967 and will probably continue to increase in the future; The overall percentage of older patients in smaller hospitals has dropped steadily since 1967, but smaller hospitals continue to have a higher percentage of older admissions than do larger hospitals; The aged have a different seasonal pattern of admission compared to younger persons, reaching a nadir in August and an apex between January and April. The average inpatient length of stay for the aged has been dropping steadily over the last twenty years, long before the recent cost containment emphasis; Community hospitals are expanding their operations into long-term care services, including skilled nursing home care, intermediate care, and psychiatric long-term care; Emphasis on early patient discharge has led many hospitals to concentrate on continuity of care between institutions and the community, including increased emphasis on discharge planning and the coordination of services; and Hospitals plan to continue to expand care for the aging and aged population. As the population of the nation ages, hospitals will increasingly address the needs of older persons and continue to plan actively and aggressively and market their services to the aged, not only for humanitarian reasons but also for survival in an increasingly competitive environment. In the future, hospitals seem likely to continue to acquire new and more costly technology to enhance their acute care delivery. At the same time, however, they will continue to provide an increasing array of health care services to older persons. They will convert acute care beds to long-term care use, construct and or purchase nursing homes, and expand into other areas of care for the aged. Thus, the authors predict that hospitals will indeed evolve beyond acute care and play a central function in the provision of the nation's long-term care system.

Aged↗

Morphological findings contributing to a failed Fontan procedure. Twelve-year experience.

A group of 37 patients (age range, 3 months to 29 years) who died after the modified Fontan procedure (within 2 months), representing 15% of the 245 patients undergoing this procedure from 1976 through 1988, was reviewed to determine the causes of death. The three morphological groups were 1) univentricular atrioventricular connection (n = 19), 2) tricuspid atresia (n = 9), and 3) other complex malformations (n = 9). Subaortic stenosis was present in 15 patients (40%) in this group compared with 31 of 208 early survivors (15%) (p = 0.008). Pulmonary artery banding, identified as a risk factor in our previous experience, was performed in 14 patients, nine of whom had subaortic stenosis. Nine palliative procedures for subaortic stenosis were performed in eight patients--before the Fontan procedure in three patients and concurrently with the Fontan procedure in five patients. Myocardial hypertrophy and signs of acute ischemic injury were common findings at autopsy (n = 25) and were particularly prominent in all patients with univentricular heart of left ventricular morphology associated with subaortic stenosis and previous pulmonary artery banding (n = 7). We conclude that the present majority of deaths occurring after the modified Fontan procedure are myocardial in nature and attributable to advanced myocardial hypertrophy that is potentiated by previous pulmonary artery banding and subaortic stenosis.

Aortic Valve Stenosis↗

HLA-DP genotyping in HLA-A,B, and DR identical intrafamilial bone marrow transplantation.

In a study carried out for patients receiving intrafamilial HLA-A,B,DR identical, MLC negative bone marrow transplants, RFLP profiles of HLA-class II for 27 donor recipient pairs were analyzed. Twenty-four pairs were found HLA-class II identical while three pairs were HLA-DP incompatible. The patients of these three pairs did not reveal any acute GVHD greater than or equal to grade II. The seven cases of acute GVHD greater than or equal to grade II found in our panel were HLA-DR, DQ, and DP compatible. Thus, in practical terms pretransplantation HLA-DP typing does not seem necessary for intrafamilial HLA-identical, MLC negative BMT. On the other hand, this work confirmed that it is possible to type for HLA-DP using molecular biological techniques, and this in itself may have some important implications for unrelated BMT.

Adolescent↗