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Biomedical subjects

J Schulman

Publications and source records attributed to J Schulman.

At least 19 recordsLinked to original sources
PubMed1995

Blood cardioplegia in the senescent heart.

As an increasingly aged population undergoes cardiac surgery, myocardial protective strategies must address the fundamental differences between adult and senescent myocardium. In a test of the hypothesis that senescent myocardium is less tolerant of cardioplegic arrest, adult (0.5 to 1.0 years) and senescent (6 to 9 years) sheep underwent 55 minutes of hypothermic blood cardioplegic arrest. A 5-minute dose of terminal warm blood cardioplegic solution was administered followed by 30 minutes of vented reperfusion. Left ventricular volume was monitored by means of sonomicrometric crystals in three orthogonal planes. Myocardial function was assessed with the preload recruitable stroke work relationship. Diastolic function was assessed with two techniques: the "stiffness" coefficient (beta), derived from the exponential end-diastolic pressure-volume relationship, and the time constant of isovolumic left ventricular pressure decay (tau). Data were acquired before arrest and after the reperfusion period. Contractility in the adult hearts was well preserved (preload recruitable stroke work: 63.7 +/- 6.1 versus 56.8 +/- 4.1 mJ/beat per milliliter per 100 gm, prearrest versus postarrest, p = not significant). In contrast, senescent heart contractility was poorly preserved (56.8 +/- 4.1 versus 35.4 +/- 4.2 mJ/beat per milliliter per 100 gm, p < 0.025). Early diastolic relaxation (tau) was prolonged in the adult hearts (42.5 +/- 3.3 versus 48.8 +/- 3.5 msec prearrest versus postarrest, p < 0.05), whereas the senescent hearts were essentially unchanged (49.3 +/- 3.1 versus 52.3 +/- 4.5 msec. p = 0.35). Myocardial stiffness (beta) was unchanged in both groups. When compared with adult hearts, contractility in senescent hearts is poorly preserved after cold blood cardioplegic arrest. Active diastolic relaxation, however, is more prolonged in adult hearts. Passive diastolic properties are unchanged in both groups. Because there are specific age-related differences in tolerance to cardioplegic arrest, extrapolation of myocardial protective strategies from studies in adult hearts to elderly patients may not be appropriate.

Aging↗
PubMed1994

Intact antiinfluenza virus immune response in targeted kappa-deficient mice.

Immunoglobulins are encoded by genes located in three different loci, the heavy chain (IgH), kappa light chain (Ig kappa), and lambda light chain (Ig lambda) loci. In mice, the kappa/lambda ratio of B cells is 95:5. In a previous study, we reported that kappa gene deletion causes the alternative usage of lambda 1 (93%) and lambda 2 (7%) light chains, and that the kappa anti-TNP repertoire is compensated for by the lambda repertoire even though the latter is clonally restricted in K-/- mice. To investigate the contribution of lambda antibodies to protection against virus, we compared K-/- mice with 129/Sv wild-type mice with respect to immune responses to influenza virus. PR8 virus immunized K-/- and 129/Sv mice showed no difference in the titer of anti-HA antibodies. Furthermore, the same immunized mice had sufficiently high neutralizing antibody titer to prevent infection when challenged with 7.5 x 10(4) TCID50 of PR8 virus. In addition, immunized K-/- mice were resistant to infection with 7.5 x 10(4) TCID50 and 7.5 x 10(5) TCID50 (10 and 100 LD50, respectively) of PR8 virus. Finally, K-/- mice are also capable of inducing cytotoxic T cells. These results suggest that the lambda repertoire can compensate for the kappa repertoire by generating a fully protective neutralizing antibody response.

Amino Acid Sequence↗
PubMed1993

Surveillance for and comparison of birth defect prevalences in two geographic areas--United States, 1983-88.

PROBLEM/CONDITION: CDC and a number of states have developed surveillance systems to monitor the birth prevalence of major defects. REPORTING PERIOD COVERED: This report covers birth defects surveillance in Metropolitan Atlanta, Georgia and selected jurisdictions in California for the years 1983-1988. DESCRIPTION OF SYSTEM: The California Birth Defects Monitoring Program and the Metropolitan Atlanta Congenital Defects Program are two population based surveillance systems that employ similar data collection methods. The prevalence estimates for 44 diagnostic categories are based on data from 1983 to 1988 for 639,837 births in California and 152,970 births in metropolitan Atlanta. The prevalences in the two areas are compared adjusting for race, sex and maternal age using Poisson regression. RESULTS: Regional differences in the prevalence of aortic stenosis, fetal alcohol syndrome, hip dislocation/dysplasia, microcephalus, obstruction of the kidney/ureter, and scoliosis/lordosis may be attributable to general diagnostic variability. However, differences in the prevalences of arm/hand limb reduction, encephalocele, spina bifida, or trisomy 21 (Down Syndrome) are probably not attributable to differences in ascertainment because these defects are relatively easy to diagnose. INTERPRETATION: Regional differences in prenatal diagnosis and pregnancy termination may affect prevalences of trisomy 21 and spina bifida. However, the reason for differences in arm/hand limb reduction is unknown, but may be related to variability in environmental exposure, heterogeneity in gene pool, or random variation. ACTIONS TAKEN: Because of the similarities of these data bases, several collaborative studies are being implemented. In particular, the differences in the birth prevalence of spina bifida and Down Syndrome will focus attention on the impact of prenatal diagnosis.

California↗
PubMed1993

Interpoint squared distance as a measure of spatial clustering.

The expectation and variance for the mean interpoint squared distance are presented. In order to evaluate these expressions it is necessary to calculate the moments of a bivariate uniform distribution defined over an arbitrary polygon. Expressions for these moments are presented, allowing the mean interpoint squared distance to be used as a measure of spatial clustering. The distribution and power of this test statistic is explored on the unit square, and the spatial distribution of 11 cases of non-Hodgkin's lymphoma is investigated to illustrate an application of the approach.

Cluster Analysis↗
PubMed1993

Induction of antihemagglutinin antibodies by polyclonal antiidiotype antibodies.

Antiidiotypic antibodies can be envisioned as an alternative approach in the development of vaccines against influenza virus, which exhibits natural antigenic variations. In our work, we obtained two polyclonal cross-reactive anti-Id antibodies against PY102, VM113, and VM202 mAbs, which in turn are specific respectively for PR8 virus and laboratory-induced virus variants (PY102-V1 and VM113-V1). With these cross-reactive anti-Id antibodies, we were able to elicit anti-HA antibodies in mice. In comparing the anti-HA antibody response in animals injected with anti-Id antibodies to those immunized with PR8 influenza virus, we demonstrated that the HI titer was higher after virus immunization and that the PR8 virus boost was more efficient in this group. Our results showed that the polyclonal cross-reactive anti-Id antibodies were more efficient than the individual anti-Ids at eliciting responses. At the same time, we demonstrated that PR8-primed T cells, cultured with B cells from animals immunized with anti-Id antibodies, were able to produce anti-PR8 antibodies subsequent to stimulation with influenza virus.

Animals↗
PubMed1993

Glycosylation of neuraminidase determines the neurovirulence of influenza A/WSN/33 virus.

The neuraminidase (NA) gene of influenza A/WSN/33 (WSN) virus has previously been shown to be associated with neurovirulence in mice and growth in Madin-Darby bovine kidney (MDBK) cells. Nucleotide sequence analysis has indicated that the NA of WSN virus lacks a conserved glycosylation site at position 130 (corresponding to position 146 in the N2 subtype). To investigate the role of this carbohydrate in viral pathogenicity, we used reverse genetics methods to generate a Glyc+ mutant virus, in which the glycosylation site Asn-130 was introduced into the WSN virus NA. Unlike the wild-type WSN virus, the Glyc+ mutant virus did not undergo multicycle replication in MDBK cells in the absence of trypsin, presumably because of lack of cleavage activation of infectivity. In contrast, revertant viruses derived from the Glyc+ mutant were able to replicate in MDBK cells without exogenous protease. Nucleotide sequence analysis revealed that the NAs of the revertant viruses had lost the introduced glycosylation site. In contrast to wild-type and revertant viruses, the Glyc+ mutant virus was not able to multiply in mouse brain. These results suggest that the absence of a glycosylation site at position 130 of the NA plays a key role in the neurovirulence of WSN virus in mice.

Animals↗
PubMed1992

Cells expressing an H chain Ig gene carrying a viral T cell epitope are lysed by specific cytolytic T cells.

The epitope corresponding to amino acid residues 147-161 of the nucleoprotein (NP) of influenza A virus is recognized by CTL in association with H-2Kd class I Ag. Herein, we engineered an Ig molecule carrying this CTL epitope by replacing the diversity gene segment of the H chain V region of an anti-arsonate antibody with an oligonucleotide that encodes the CTL epitope. The chimeric H chain gene was expressed either alone or together with the parental L chain in the nonsecreting BALB/c myeloma B cell line, SP2/0. The Ig produced by cells transfected with both the chimeric H chain and parental L chains genes expressed the NP epitope but lost the original arsonate binding activity. In addition, SP2/0 cells expressing the chimeric H chain either alone or together with the parental L chain were lysed by class I restricted NP-epitope specific CTL. By contrast, SP2/0 cells pulsed with soluble chimeric Ig molecules were not lysed by the specific CTL. These observations indicate that: 1) this particular CTL epitope can be expressed on Ig molecules without altering the H and L chain pairing; 2) this CTL epitope can be generated from this chimeric Ig in which it is surrounded by flanking regions distinct from those of the viral NP; and 3) the generation of this CTL epitope from the Ig molecule requires the endogenous pathway as do viral proteins.

Amino Acid Sequence↗
PubMed1992

Cytogenetic results from the U.S. Collaborative Study on CVS.

Cytogenetic data are presented for 11,473 chorionic villus sampling (CVS) procedures from nine centres in the U.S. NICHD collaborative study. A successful cytogenetic diagnosis was obtained in 99.7 per cent of cases, with data obtained from the direct method only (26 per cent), culture method only (42 per cent), or a combination of both (32 per cent). A total of 1.1 per cent of patients had a second CVS or amniocentesis procedure for reasons related to the cytogenetic diagnostic procedure, including laboratory failures (27 cases), maternal cell contamination (4 cases), or mosaic or ambiguous cytogenetic results (98 cases). There were no diagnostic errors involving trisomies for chromosomes 21, 18, and 13. For sex chromosome aneuploidies, one patient terminated her pregnancy on the basis of non-mosaic 47,XXX in the direct method prior to the availability of results from cultured cells. Subsequent analysis of the CVS cultures and fetal tissues showed only normal female cells. Other false-positive predictions involving non-mosaic aneuploidies (n = 13) were observed in the direct or culture method, but these cases involved rare aneuploidies: four cases of tetraploidy, two cases of trisomy 7, and one case each of trisomies 3, 8, 11, 15, 16, 20, and 22. This indicates that rare aneuploidies observed in the direct or culture method should be subjected to follow-up by amniocentesis. Two cases of unbalanced structural abnormalities detected in the direct method were not confirmed in cultured CVS or amniotic fluid. In addition, one structural rearrangement was misinterpreted as unbalanced from the direct method, leading to pregnancy termination prior to results from cultured cells showing a balanced, inherited translocation. False-negative results (n = 8) were observed only in the direct method, including one non-mosaic fetal abnormality (trisomy 18) detected by the culture method and seven cases of fetal mosaicism (all detected by the culture method). Mosaicism was observed in 0.8 per cent of all cases, while pseudomosaicism (including single trisomic cells) was observed in 1.6 per cent of cases. Mosaicism was observed with equal frequency in the direct and culture methods, but was confirmed as fetal mosaicism more often in cases from the culture method (24 per cent) than in cases from the direct method (10 per cent). The overall rate of maternal cell contamination was 1.8 per cent for the culture method, but there was only one case of incorrect sex prediction due to complete maternal cell contamination which resulted in the birth of a normal male.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Distance and risk measures for the analysis of spatial data: a study of childhood cancers.

Three statistical approaches, used to detect spatial clusters of disease associated with a point source exposure, are applied to childhood cancer data for the city of San Francisco (1973-88). The distributions of incident cases of leukemia (51 cases), brain cancer (35 cases), and lymphatic cancer (37 cases) among individuals less than 21 years of age are described using three measures of clustering: distance on a geopolitical map, distance on a density equalized transformed map, and relative risk. The point source of exposure investigated is a large microwave tower located southwest of the center of the city (Sutro Tower). The three analytic approaches indicate that the patterns of the major childhood cancers are essentially random with respect to the point source. These results and a statistical model for spatial clustering are used to explore distance and risk measures in the analysis of spatial data. Both types of measures of spatial clustering are shown to perform similarly when a specific area of exposure can be defined.

Adolescent↗
PubMed1992

Cost efficient sampling design for quality control of a birth defects registry.

Quality control studies of registries are frequently conducted. We employed a cost effective sampling scheme for assessing the quality of case identification and abstracting in one birth defects registry. The general sampling method was a stratified two-stage design, and the optimal sample size for each stratum was chosen to minimize cost, which was defined as time for data collection. The resulting sample sizes depended on the variability in the number of abstracts between and within data collection facilities, and the amount of time needed to complete each data collection step. The most time effective scheme was to visit several facilities each for a short period of time rather than fewer facilities for a longer period of time. Cost efficient sampling strategies, such as the method used here, can be applied to ensure precision in registry quality control analyses and other public health studies.

Congenital Abnormalities↗
PubMed1992

Reporting and selection bias in case-control studies of congenital malformations.

Retrospective studies of congenital malformations frequently rely on exposures reported by study subjects. Differential error in exposure reporting by cases and controls, which has alternatively been referred to as "recall bias" and "reporting bias," may result in a biased effect measure. Some authors have attempted to avoid reporting bias by comparing exposures between two malformed groups, rather than between cases and nonmalformed controls. This approach, however, may introduce its own bias, which we call selection bias. Both reporting bias and selection bias are shown to be algebraically equivalent to bias arising from exposure misclassification. The magnitudes of these biases are compared for a range of plausible parametric values. The case-control design is sensitive to both differential reporting and selection bias, and the choice of study design involves balancing these two sources of bias.

Case-Control Studies↗
PubMed1991

Inhibition of multicycle influenza virus replication by hybrid antibody-directed cytotoxic T lymphocyte lysis.

Bifunctional antibodies with specificity for the TCR/CD3 complex as well as to a target cell-surface Ag can redirect CTL to lyse the target cell. We have produced a hybrid hybridoma, HHA6, which secretes bifunctional antibodies capable of redirecting CTL to lyse influenza virus-infected target cells. When added along with CTL to virus-infected cells, these antibodies very efficiently inhibit multicycle virus replication. Because hybrid hybridomas reassort H and L chains randomly we attempted to purify bifunctional antibody by using HPLC. The purification increased the potency of HHA6. This increase probably reflects an enrichment of the active species and the removal of inhibiting antibody species.

Animals↗
PubMed1990

Multicentric angiofollicular lymph node hyperplasia with peripheral neuropathy, pseudotumor cerebri, IgA dysproteinemia, and thrombocytosis in women. A distinct syndrome.

Four women with multicentric angiofollicular lymph node hyperplasia had a distinct clinical syndrome characterized by peripheral neuropathy, pseudotumor cerebri, IgA dysproteinemia, and thrombocytosis. The nodes displayed typical morphologic changes of the plasma cell variant of multicentric angiofollicular lymph node hyperplasia. The pathologic changes are morphologically distinct from angioimmunoblastic lymphadenopathy with dysproteinemia although clinical similarities do exist. In these four cases, the lymphadenopathy was usually bulky and multicentric. There was frequent splenic involvement. The neuropathies were severe and disabling. Clinical courses have been variable with some responses to therapy with steroids and alkylating agents. No neoplastic transformations have occurred. Multicentric angiofollicular lymph node hyperplasia may represent a reactive lesion in which the antigenic stimulus is unknown but results in follicular hyperplasia, angiogenesis, and the systemic manifestations of hyperimmune stimulation. We believe this clinical syndrome may represent a distinct variant of multicentric angiofollicular lymph node hyperplasia, and it requires close observation for neoplastic transformation and other complications of its multisystem nature.

Biopsy↗
PubMed1990

Sudden infant death syndrome among Asians in California.

We analyzed California linked birth and infant death records for 1978 to 1985 to determine the ethnic-specific incidence of sudden infant death syndrome in five Asian-American subgroups, and to assess the association of sudden infant death syndrome with cultural assimilation. The overall incidence of sudden infant death syndrome for these groups was 1.1/1000 live births (194 cases). The ethnic-specific incidence was statistically associated with the immigration status of each ethnic group, as measured by the proportion of all live births for which the mother was born in the United States, with a higher incidence for groups that have been in the United States for the longest period. A logistic model was used to examine simultaneously the association of sudden infant death syndrome with maternal ethnicity, ethnic homogeneity or heterogeneity of the parents, and maternal birthplace (United States, or elsewhere). The logistic analysis did not yield statistically significant evidence to support cultural assimilation as a factor in the incidence of sudden infant death syndrome for these groups. This finding may be due to small sample size and inadequate indicators of assimilation. It may also be that other factors relating to immigration and selective migration affect the incidence of sudden infant death syndrome among Asian-Americans.

Adult↗
PubMed1989

Pyometra involving uterus masculinus in a cat.

A neutered male cat with a history of intermittent antibiotic-responsive fever and strangury had pyometra involving uterus masculinus. The infected structure was removed, and episodes of infection and strangury ceased.

Animals↗
PubMed1989

Sudden infant death syndrome and birth weight.

We studied 2962 cases of sudden infant death syndrome (SIDS), derived from linked birth and death records, to specify further the descriptive epidemiologic data on recognized SIDS risk factors and to examine interrelationships among multiple risk factors and SIDS while controlling for the influence of birth weight (using logistic regression). The results generally confirmed those of other studies, with the exception of a higher incidence of SIDS among Chinese and Japanese babies and a lower incidence among Hispanic babies, all in comparison with white, non-Spanish (Anglo) infants. Median age at death was found to vary by birth weight, with very low birth weight babies being about 6 weeks older (postnatal age) than normal birth weight babies at time of death. The association of the risk factors with SIDS remained when birth weight data were statistically controlled; the association of these risk factors with SIDS cannot be explained by their relationship to birth weight. An interaction was found between race and maternal age and between multiparity and type of hospital of birth. There was no interaction between birth weight and the other risk factors.

Birth Weight↗
PubMed1989

Nucleotide changes in sequential variants of influenza virus hemagglutinin genes and molecular structures of corresponding monoclonal antibodies specific for each variant.

We have generated four monoclonal antibodies specific for one or more members of a series of two sequentially derived PR8 influenza virus variants. Three of these antibodies share cross-reactive idiotypes. The amino acid sequences of these antibodies were determined, and it was found that two of these antibodies use genes from the VH7183 family, whereas the third uses a gene from the VHJ558 family. All four monoclonal antibodies derive from different families of genes encoding the variable region of the kappa chain. The RNA sequence of the parent PR8 virus as well as the RNA sequences of the sequential variants were also determined, and it was demonstrated that the variant hemagglutinin molecules differed from the parent molecule by only a single amino acid interchange. Despite these subtle differences in antigenic structures of hemagglutinin, and the cross-reactive idiotype of the antibodies, their primary structures were very different. These data reinforce the idea that a wide variety of antibody structures exist which are directed against subtly different structures in biologically important antigens.

Amino Acid Sequence↗