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R Kaufman

Publications and source records attributed to R Kaufman.

At least 37 records · Page 2Linked to original sources
PubMed1996

Catabolism of dopamine and 5-hydroxytryptamine by monoamine oxidase in the ixodid tick, Amblyomma hebraeum.

The purpose of this study was to assess biogenic amine catabolism in Amblyomma hebraeum Koch (an African cattle tick). We assayed haemolymph and saliva for a variety of biogenic amines (usually following injection of substrate into the haemolymph) in partially fed females using HPLC coupled to electrochemical detection. Dopamine (DA) and 5-hydroxytryptamine (5-HT) were rapidly converted to dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) respectively, indicating that monoamine oxidase (MAO) constitutes a major catabolic pathway for biogenic amines in this species. We could not detect N-acetylated or gamma-glutamyl conjugated metabolites of these important neurotransmitters. [In a few samples we looked for but could not detect homovanillic acid or 3-methoxytyramine (O-methylated metabolites of DOPAC and DA respectively).] Deprenyl was about 44-72 times more potent an inhibitor of MAO than clorgyline when either DA or 5-HT was offered as substrate, suggesting that this MAO is of the MAOB type. Conversion of DA to DOPAC was also detected in several tissues incubated with DA in vitro; in descending order of MAO activity (pmol mg-1 h-1 at about 18 degrees C) tissues tested were: skeletal muscle (approximately 100), Malpighian tubule (approximately 50), ovary (approximately 45), salivary gland (approximately 30), midgut (approximately 20), and haemolymph (approximately 4-5). This study suggests that ticks differ considerably from insects in utilizing MAO as an important metabolic pathway for biogenic amines.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

A generalized HLA prediction model for related donor matches.

This article derives a generalized probabilistic model for predicting HLA matches from a population of family members consisting of all blood-related descendants of one pair of patient's grandparents, excluding parents and siblings, for three subsequent generations. This consists of the patient's children, blood-related aunts/uncles, first cousins, first cousins once removed and nephews/nieces. (It is assumed that the patient's siblings and parents were tested prior but did not produce a match.) The model uses family pedigree information and haplotype frequency data to estimate the likelihood of a match. Results are given for many ethnic groupings. These results indicate that such a family search frequently approximates or exceeds the 0.25 success rate of a single sibling search when the patient possesses a common haplotype within the patient's ethnic population, and the family members are also of the same ethnic origin. Families of the same lineage averaging more than two children/nuclear family substantially exceed the 0.25 rate. The results degrade only modestly for the two children/nuclear family scenario when first cousins once removed are excluded from the search. Among the study's larger nations of Japan, the United States and the United Kingdom, approximately 15-20% of the population can potentially benefit from such searches. These percentages are much higher for the study's smaller countries.

HLA Antigens↗
PubMed1996

Increased bcl-2 protein levels in prostatic adenocarcinomas are not associated with rearrangements in the 2.8 kb major breakpoint region or with p53 protein accumulation.

bcl-2, an inhibitor of programmed cell death (apoptosis), is present in high levels in a subset of prostatic adenocarcinomas. In this study, 42 prostatic adenocarcinomas were analyzed to determine whether increased bcl-2 levels are associated with rearrangements in the 2.8-kb major breakpoint region, an association known to occur in certain follicular lymphomas featuring a t(14:18) translocation. Immunostaining for bcl-2 and p53 proteins was performed on formalin-fixed, paraffin-embedded tumor specimens using murine anti-human bcl-2 and p53 monoclonal antibodies in all 42 cases. Genomic DNA from paired frozen samples of each tumor was subjected to digestion with HindIII and EcoRI and the products analyzed on a Southern blot with a 2.8-kb-digoxigenin-labeled major breakpoint region probe. Comparisons between groups were evaluated with the Fisher exact test. Diffuse, strong cytoplasmic immunoreactivity for bcl-2 was present in the epithelial cells of tumor glands in 16 of 42 cases (38%), including 8 of 19 low grade (Gleason score 6 and below) and 8 of 23 high grade (Gleason score 7 and above) prostatic adenocarcinoma. Southern blotting demonstrated a normal 2.8-kb germline DNA fragment in every case, with no evidence of rearrangement. Nuclear p53 staining was present in 10 of 24 high grade and 0 of 18 low grade tumors (P < 0.001). Only four cases exhibited positivity for both bcl-2 and p53, and there was no association of bcl-2 positivity with co-expression of the p53 protein (P = 0.58). We conclude that aberrations in the function of either bcl-2 or p53 could possibly modify the apoptotic pathway resulting in the extended survival of tumor cells. Also, increased bcl-2 levels in prostatic adenocarcinomas occur in the absence of detectable rearrangements in the major breakpoint region.

Adenocarcinoma↗
PubMed1995

Measles virus and C3 binding sites are distinct on membrane cofactor protein (CD46).

The human complement regulatory protein membrane cofactor protein (CD46) is the cellular receptor for measles virus (MV), whereas decay accelerating factor (DAF; CD55), a structurally similar complement regulatory protein, does not bind MV. To characterize the interaction between MV and CD46, mutants of the CD46 protein and hybrid molecules between CD46 and DAF were tested for their ability to act as MV receptors. The transmembrane domain and cytoplasmic tail of CD46 were not required for receptor function as cells expressing the CD46 extracellular domain linked to the glycosyl-phosphatidylinositol tail of DAF were rendered susceptible to MV infection. Chimeric proteins exchanging the four extracellular short consensus repeat (SCR) domains between CD46 and DAF indicated that only molecules with both SCR1 and SCR2 from CD46 allowed a productive MV infection. Further, monoclonal antibodies (mAbs) against SCR1 or SCR2 of CD46 blocked MV infection, whereas a mAb against SCR3 and SCR4 did not. The latter mAb blocks C3b/C4b binding (which maps to SCR3 and SCR4) whereas the former mAbs do not. Thus, our data indicate that both SCR1 and SCR2 make up the MV receptor determinant in CD46. These results also suggest avenues for development of therapeutic agents to inhibit MV binding and thus infection and disease.

Animals↗
PubMed1995

Characterization of the echovirus 7 receptor: domains of CD55 critical for virus binding.

CD55, or decay-accelerating factor (DAF), is a cell surface glycoprotein which regulates complement activity by accelerating the decay of C3/C5 convertases. Recently, we and others have established that this molecule acts as a cellular receptor for echovirus 7 and related viruses. DAF consists of five domains: four short consensus repeats (SCRs) and a serine/threonine-rich region, attached to the cell surface by a glycosylphosphatidyl inositol anchor. Chinese hamster ovary cells stably transfected with deletion mutants of DAF or DAF-membrane cofactor protein recombinants were analyzed for virus binding. The results indicate that the binding of echovirus 7 to DAF specifically requires SCR2, SCR3, and SCR4. There is also a nonspecific requirement for the S/T-rich region which probably functions to project the binding region away from the cell membrane. The three nonpeptide modifications of DAF, N-linked glycosylation, O-linked glycosylation, and the glycosylphosphatidyl inositol anchor, are not required for virus binding. The SCRs of membrane cofactor protein, the closest known relative of DAF, cannot substitute for those of DAF with retention of virus binding activity. The monoclonal antibody used to identify DAF as an echovirus receptor, and which inhibits binding of the virus (monoclonal antibody 854), binds to SCR3.

Animals↗
PubMed1995

HLA prediction model for extended family matches.

This article derives a probabilistic model for predicting HLA matches from a population of extended family members. (Extended family members are defined as either first cousins or blood-related aunts or uncles). The model uses family pedigree information and haplotype frequency data to estimate the likelihood of a match. Results are given for many ethnic groupings. A case study is also described. This technique is most applicable when all family members are of the same ethnic origin, which increases the likelihood of a match among a small number of family members, and the patient possesses a haplotype having a frequency exceeding 10%, within the patient's ethnic population. Under such conditions, an extended family search can frequently approximate the success rate of a single sibling search.

Adult↗
PubMed1994

Comparison of three immunoassays for the determination of N-acetylprocainamide. Determination of false elevations by a polyclonal antibody-based method.

The performance of the ROCHE FP NAPA reagent, a newly reformulated monoclonal antibody-based fluorescence polarization immunoassay (FPIA) for N-acetylprocainamide, was compared with two commercially available polyclonal antibody-based immunoassays, the Abbott TDx and Syva EMIT. Although excellent correlation was observed between the ROCHE FP NAPA reagent and the Syva EMIT reagent, a positive bias was observed in the correlation between the ROCHE FP NAPA reagent and the Abbott TDx reagent. The bias in the TDx method was investigated further by the concurrent high-performance liquid chromatography (HPLC) analysis of patient samples. Insignificant differences (p < 0.05) were observed between the HPLC and ROCHE FP values. The TDx system, however, yielded significantly higher (p < 0.0005) results than did HPLC.

Acecainide↗
PubMed1994

Inclusion of a sensitivity control to add a quality-control parameter and improve reproducibility in BCR, immunoglobulin, and T-cell receptor gene-rearrangement studies.

Molecular analyses to determine clonality of T and B cells in malignant lymphoma and leukemia and to detect the (9;22) translocation in chronic myelogenous leukemia are commonly used in clinical molecular biology laboratories. We describe the inclusion of a sensitivity control in each of these assays derived from DNA of well-characterized cell lines. The inclusion of such a sample adds an important quality-control parameter to ensure assay-to-assay reproducibility and to satisfy accreditation and regulatory requirements.

Blotting, Southern↗
PubMed1994

Utilization of pulmonary function tests by primary care internists in a community hospital.

OBJECTIVE: A quality assurance effort to evaluate the use of pulmonary function tests by primary care physicians. Specifically, to examine the patient's understanding of the test, the types of tests physicians order, and the appropriateness of the ordered tests for answering questions posed by physicians. DESIGN: Concurrent chart review, clinical interviews, and patient interviews. SETTING: Community teaching hospital. PATIENTS: 101 consecutive inpatients and outpatients, referred to the Pulmonary Function Laboratory over a consecutive 5-month period. MEASUREMENTS: Interview of the patient by a pulmonary technician. Interview of the primary care physician by a pulmonary physician. Interview, where applicable, with the house staff. Final assessment by a pulmonary physician. MAIN RESULTS: 64% of the patients understood the purpose of the test and 49% of the patients felt there was some potential benefit to be derived from participating in the testing. Sixty-five percent of the physicians ordered specific tests on their patients. Seventy-two percent of physicians planned on using the data obtained from testing to formulate treatment decisions. Fifty percent of the interviewed physicians said they were using the results for decisions regarding further diagnostic evaluation and/or treatment. The reviewing pulmonary physician considered that 31% of the pulmonary function tests ordered were appropriate for the goals defined by the requesting physician. Sixty-eight percent of the ordered tests could have had some aspects of ordering improved, and 1% of the testing was unnecessary. CONCLUSIONS: 1) There is a need to increase patient understanding of the indications and potential benefits of participating in pulmonary function testing. 2) When physicians-in-training are involved in the process of requesting pulmonary function tests, greater staff-level supervision and involvement should be present. 3) There is a need to increase physician knowledge regarding the appropriate pulmonary function tests that should be requested for specific clinical questions and situations. 4) The requesting form for pulmonary function testing may serve to remind and educate the physician, while documenting the indications for the testing and the physician's efforts. 5) Quality assurance/utilization-review efforts can be combined with educational efforts that could result in a diminution of the deficiencies.

Adult↗
PubMed1993

Cancer Information Service utilization by selected U.S. ethnic groups.

The Cancer Information Service (CIS) has responded to information requests of more than 5 million people since 1976. Of interest to staff has been program coverage--in particular, patterns of use by audiences identified as being at high risk for cancer. This paper presents an introductory analysis of the use of the CIS between 1983 and 1990 by ethnic and racial groups. Data analysis, although affected by demographic data-collection restrictions, confirms suspected underutilization by racial and ethnic minorities. Although members of minority audiences call the CIS less frequently, they use the CIS for information about cancer-prevention topics more often than they do for treatment information, and their calls tend to be longer than calls from Whites. Television is demonstrated to be the most effective medium to stimulate use of the CIS among all audience groups. The authors conclude that expanding program coverage is important to reach target audiences, as is a more rigorous data-collection plan to assess utilization patterns. They also suggest the use of program funds to buy air time on a regular basis to stimulate use of the CIS by high-risk audiences and the general public.

Ethnicity↗
PubMed1993

Benign vulvar melanosis.

Large melanotic lesions of the vulva are uncommon, but they may present a diagnostic problem. Eleven cases of benign vulvar melanosis are reported. The clinical features, histologic characteristics and differential diagnosis are described and analyzed.

Adult↗
PubMed1993

Long-term suppression of recurrent genital herpes with acyclovir. A 5-year benchmark. Acyclovir Study Group.

BACKGROUND AND DESIGN: This multicenter trial (19 sites) was initiated in 1984 in more than 1100 immunocompetent individuals with a history of frequently recurring genital herpes (mean, > or = 12 episodes per year). The first year of this suppressive therapy trial was placebo controlled, with acyclovir being provided for episodic treatment in both groups. Thereafter, patients were treated with open-label acyclovir suppressive therapy on a long-term basis (400 mg twice daily) to continue to assess its long-term safety and efficacy. Complete data are available on 389 of the 430 patients who began the fifth year of the study. RESULTS: Patients were seen quarterly for review of diaries and clinical laboratory evaluations. The percentage of patients recurrence free for any 3-month quarter of the fifth year ranged from 86% to 90%. The mean annual number of recurrences per patient declined from 1.7 during the first year to 0.8 during the fifth year of suppressive therapy. The frequency of false prodromes has also decreased over time. More than 20% of the patients receiving suppressive therapy for 5 years have been recurrence free the entire time. The duration of herpetic outbreaks during suppressive therapy has not changed. CONCLUSION: This study extends the safety and efficacy profile of oral acyclovir in the suppression of genital herpes to 5 years. The majority of the patients were recurrence free on an annual basis during suppressive therapy. Therapy was well tolerated. Acyclovir usage was not associated with serious side effects or cumulative toxicity.

Acyclovir↗
PubMed1992

Detection of bluetongue virus serogroup by polymerase chain reaction.

To facilitate detection of active bluetongue virus (BTV) infection, a polymerase chain reaction (PCR) protocol was developed. The BTV reverse transcriptase PCR (RT-PCR) is a 1-tube reaction and involves chemical denaturation of the double-stranded viral RNA target, a complementary DNA (cDNA) synthesis step, and PCR amplification of the cDNA. BTV RT-PCR using primers derived from highly conserved genome segment 10 results in a 251-base pair (bp) product. BTV RNA from all USA prototype serotypes 2, 10, 11, 13, and 17; a wide spectrum of USA BTV field isolates including serotypes 10, 11, 13, and 17; and a spectrum of Israeli field isolates including serotypes 2, 4, 6, 10, and 16 were detected by BTV RT-PCR. With agarose gels, the 251-bp product was detected from as little as 100 fg-1 pg of BTV RNA, which is equivalent to 5 x 10(3)-5 x 10(4) viral particles or 5 x 10(2)-5 x 10(3) infectious units. With dot blot hybridization, specific PCR product was detected from as little as 1 fg of BTV RNA, which is equivalent to 50 viral particles, or 5 infectious units. This level of sensitivity is comparable to that of virus isolation. The BTV RT-PCR using primers derived from genome segment 10 can detect a wide spectrum of USA and Israeli BTV serotypes and has potential for detection of infection by the BTV serogroup. Application of this BTV PCR to clinical samples is in progress.

Base Sequence↗
PubMed1991

Expression and amplification of the HER-2/neu (c-erbB-2) protooncogene in epithelial ovarian tumors and cell lines.

Amplification of the c-erbB-2 protooncogene has been associated with a poor prognosis in human breast and ovarian cancers. Our study was undertaken to examine whether amplification, rearrangement, or overexpression of c-erbB-2 and other protooncogenes was frequently observed in epithelial ovarian cancers. c-erbB-2 was expressed in 87% of 22 ovarian cancers analyzed, but expression was significantly increased in only one of the 22 tumor specimens. In this case elevated c-erbB-2 expression was associated with dramatic amplification of the gene. In another tumor a 3.8 kb EcoRI fragment was found, in addition to the usual 4.4 and 6.0 kb fragments; this is consistent with a possible gene rearrangement or a restriction fragment length polymorphism. To place these results in perspective, expression of several other protooncogenes has been examined in ovarian carcinomas. The c-fos, c-myc, n-myc, c-fms, and c-Ha-ras protooncogenes were expressed in different fractions of tumors, but expression of l-myc, c-erbB, c-myb, c-sis, and c-mos was not detectable. Aside from c-erbB-2, neither amplification nor rearrangement was observed among the other protooncogenes studied. Expression of c-erbB-2, c-fms, c-myc, n-myc, c-fos, and c-Ha-ras deserves further evaluation as a prognostic factor in ovarian cancer.

Female↗
PubMed1991

Evidence of genome segment 5 reassortment in bluetongue virus field isolates.

A recombinant cDNA probe from genome segment 5 obtained from a virulent US bluetongue virus strain (BTV-11 strain UC8) was hybridized to US and Israeli BTV prototypes and field isolates. The cloned genetic probe hybridized with US BTV prototype 10, but not with US prototypes 2, 11, 13, and 17; with the avirulent BTV-11 strain UC2; and with the Israeli prototype 10. When the probe was hybridized to field isolates from the US serotypes, it hybridized to 12 of 14 BTV-10 isolates and 4 of 17 BTV-11 samples, but not to the BTV-13 and BTV-17 samples tested. Hybridization was not observed with the Israeli field isolates studied. Results indicate that a reassortant event occurred between a strain of US BTV-10 and US BTV-11 that originated the BTV-11 strain UC8.

Animals↗