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Biomedical subjects

R Kaufman

Publications and source records attributed to R Kaufman.

At least 19 recordsLinked to original sources
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↗
PubMed1990

Association of disease-free survival and percent of ideal dose in adjuvant breast chemotherapy.

The relationship between percent of ideal dose and disease-free survival was examined in 256 Stage II and III patients who participated in a 2-year breast adjuvant chemotherapy trial consisting of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) given postoperatively. When analyzed analogously to previous work, the results confirmed a dose-response relationship: that is, there appeared to be an improved disease-free survival for patients receiving higher doses of adjuvant chemotherapy. The major criticism of such an analysis is its bias. This bias was addressed by considering only patients who were still receiving therapy at 6, 12, and 24 months; then, the dose-response relationship was no longer seen. Although causality cannot be inferred, the apparent differences in disease-free survival among the dose groups can be attributed to recurrences in the first 2 years among patients receiving lower doses of chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

A naturally occurring gamma globin gene mutation enhances SP1 binding activity.

Transcription of the human fetal globin genes in erythroid cells is tightly regulated during different stages of development and differentiation. Two naturally occurring mutations 202 base pairs upstream of the duplicated gamma globin genes are associated with incorrectly regulated gamma globin gene gene expression; elevated levels of fetal globin are synthesized during adult life. A C-to-G base substitution upstream of the G gamma-globin gene is highly correlated with a dramatic increase in gene expression. It increases the similarity of the region to the consensus Sp1 recognition site. We determined that the mutated DNA had a 5- to 10-fold-higher affinity for Sp1 than did normal gamma globin gene sequence. We also observed a reduction in normal factor-binding activity. A different substitution at -202, C to T, upstream of the A gamma-globin gene was associated with a more moderate increase in fetal globin expression. This mutation decreased the similarity of the sequence to an Sp1 recognition site. We determined that it did not result in enhanced Sp1 binding but did alter normal factor binding. We suggest that these changes in nuclear protein-binding properties detected in vitro are responsible for the enhanced gamma globin gene expression found in -202 G gamma beta + patients with hereditary persistence of fetal hemoglobin.

Base Sequence↗
PubMed1989

Substituting diagnostic services. New tests only partly replace older ones.

Hospitals' patterns of ancillary service use were examined to determine whether new technologies replace older, more outmoded technologies, and to explore the factors associated with adoption of newer services and abandonment of older services. Annual inpatient use of five pairs of ancillary services was measured for 1978 through 1980 at 63 hospitals in five regions. The diagnostic test pairs consisted of one well-established diagnostic test and one newer service that could largely substitute for the older one and included (1) oral cholecystogram and gallbladder ultrasound; (2) brain scan and computed tomographic head scan; (3) skull roentgenogram and brain scan; (4) bone survey and bone scan; and (5) blood type/cross and type/screen. Use of gallbladder ultrasound increased significantly after its adoption, with small decreases in the use of oral cholecystogram, its paired test. For the other newer tests examined, increased use was not accompanied by significantly decreased use of the paired older service. The strongest predictors of change in patterns of test use were hospital size, number of residencies, occupancy, urban location, and the proportion of specialists on staff. We conclude that diffusion of new diagnostic services occurs gradually and often without concomitant decrease in older, outmoded services; new services generally seem to complement rather than substitute for older ones. Larger hospitals with a greater teaching commitment make a faster transition to the use of new technologies and the abandonment of older ones.

Diagnostic Services↗
PubMed1989

Synthesis, in vitro acetylcholine-storage-blocking activities, and biological properties of derivatives and analogues of trans-2-(4-phenylpiperidino)cyclohexanol (vesamicol).

Eighty-four analogues and derivatives of the acetylcholine-storage-blocking drug trans-2-(4-phenylpiperidino)-cyclohexanol (vesamicol) were synthesized, and their potencies were evaluated with the acetylcholine active-transport assay utilizing purified synaptic vesicles from Torpedo electric organ. The parent drug exhibits enantioselectivity, with (-)-vesamicol being 25-fold more potent than (+)-vesamicol. The atomic structure and absolute configuration of (+)-vesamicol were determined by X-ray crystallography. The absolute configuration of (-)-vesamicol is 1R,2R. Structure-activity evidence indicates that (-)-vesamicol does not act as an acetylcholine analogue. Alterations to all three rings can have large effects on potency. Unexpectedly, analogues locking the alcohol and ammonium groups trans-diequatorial or trans-diaxial both exhibit good potency. A potent benzovesamicol family has been discovered that is suitable for facile elaboration of the sort useful in affinity labeling and affinity chromatography applications. A good correlation was found between potencies as assessed by the acetylcholine transport assay and LD50 values in mouse.

Acetylcholine↗
PubMed1989

Fractional vesamicol receptor occupancy and acetylcholine active transport inhibition in synaptic vesicles.

Vesamicol [(-)-(trans)-2-(4-phenylpiperidino)cyclohexanol] receptor binding and inhibition of acetylcholine (AcCh) active transport by cholinergic synaptic vesicles that were isolated from Torpedo electric organ were studied for 23 vesamicol enantiomers, analogues, and other drugs. Use of trace [3H]vesamicol and [14C]AcCh allowed simultaneous determination of the concentrations of enantiomer, analogue, or drug required to half-saturate the vesamicol receptor (Ki) and to half-inhibit transport (IC50), respectively. Throughout a wide range of potencies for different compounds, the Ki/IC50 ratios varied from 1.5 to 24. Compounds representative of the diverse structures studied, namely deoxyvesamicol, chloroquine, and levorphanol, were competitive inhibitors of vesamicol binding. It is concluded that many drugs can bind to the vesamicol receptor and binding to only a small fraction of the receptors can result in AcCh active transport inhibition. Possible mechanisms for this effect are discussed.

Acetylcholine↗
PubMed1989

One-year suppression of frequent recurrences of genital herpes with oral acyclovir.

A double-blind, placebo-controlled study was undertaken to evaluate the long-term efficacy and safety of oral acyclovir suppressive therapy over a 1-year period. Results from the multicenter trials, based on a total of 261 patients with frequently recurring genital herpes, were analyzed. Of the patients enrolled in the study, 131 received oral acyclovir capsules (800 mg) daily and 130 received placebo capsules. Medication was taken twice daily. Analysis of data from patients who completed a full year of therapy demonstrated that only 5% of patients receiving placebo were free from recurrences, as compared with 46% of acyclovir recipients. The mean number of recurrences for patients on acyclovir therapy was 1.8, as compared with a rate of 8.7 recurrences for the placebo group over the course of the year. The mean time to the first recurrent herpes outbreaks was 19 days for the placebo group and 274 days for the acyclovir-treated patients. There were no significant differences between the two groups in laboratory data or in the frequency or nature of side effects reported. Daily administration of acyclovir capsules for 1 year is a safe and effective therapy for control of frequent recurrences of genital herpes.

Acyclovir↗
PubMed1989

Septic ischial bursitis in systemic lupus erythematosus presenting as a perirectal mass.

We describe a patient with systemic lupus erythematosus with dissection of a large ischial bursal cyst which presented as a perirectal mass. Dissecting bursal and articular synovial cysts are known to cause multiple complications including a number of "pseudosyndromes" such as pseudothrombophlebitis. The cyst in this case was initially thought to represent a perirectal abscess and we propose the term "pseudoperirectal abscess" to describe this condition. This cyst was found to be infected and required an extended course of antibiotics and bursectomy.

Abscess↗
PubMed1988

Episodic twice-daily treatment for recurrent genital herpes.

A new dosage regimen of orally administered acyclovir, 800 mg twice daily for five days, for the treatment of recurrent genital herpes was compared with the standard dosage of 200 mg given five times per day. A double-blind study of 157 patients was used to evaluate the safety and efficacy of both regimens. The new regimen was well tolerated, more convenient, and as effective as the standard dosage. In male patients, the new regimen may be more effective than the standard regimen of 200 mg given five times per day to treat lesions that are already present.

Acyclovir↗
PubMed1988

Prolonged continuous versus intermittent oral acyclovir treatment in normal adults with frequently recurring genital herpes simplex virus infection.

In Year 1 of this two-year trial, patients with six or more genital herpes recurrences in the past year received suppressive treatment with either acyclovir, 400 mg, or placebo, orally twice daily for one year, and physician-documented recurrences were treated with open-labeled acyclovir, 200 mg, orally five times per day for five days (acute treatment). In Year 2, patients received open-labeled acyclovir treatment either with daily suppressive therapy or intermittent acute therapy. Among 683 patients who completed two years of treatment, 348 received continuous suppressive treatment for two years, 276 received acute treatment in Year 1 and suppressive treatment in Year 2, 24 received suppressive treatment in Year 1 and acute treatment in Year 2, and 35 received acute treatment for two years. Patient groups receiving intermittent acute acyclovir treatment experienced means of 7.0 to 12.6 recurrences/year during treatment as compared with 1.4 to 1.9 recurrences/year among groups receiving continuous suppressive treatment. No patients who received acute treatment remained recurrence-free for two years as compared with 29 percent of patients receiving continuous acyclovir suppression for two years. There was no evidence of cumulative toxicity detected by clinical, hematologic, or blood chemistry evaluations performed monthly in Year 1 and quarterly in Year 2. Suppressive oral acyclovir therapy remained effective and well-tolerated in this two-year trial.

Acyclovir↗
PubMed1988

Ascorbic acid specifically increases type I and type III procollagen messenger RNA levels in human skin fibroblast.

In cultured human skin fibroblasts, ascorbic acid stimulates collagen production with no apparent change in the intracellular degradation of newly synthesized procollagen. To understand the basis for this effect, we measured the steady-state levels of type I and type III procollagen mRNAs in cells treated with ascorbic acid. A three- to fourfold increase in collagen synthesis was associated with a two- to threefold increase in the levels of mRNAs for both type I and type III procollagens. These effects of ascorbic acid are explained by a translational control linked either to procollagen gene transcription or mRNA degradation.

Ascorbic Acid↗