Search PubMed⌕ Search

Biomedical subjects

S Birnbaum

Publications and source records attributed to S Birnbaum.

At least 37 records · Page 2Linked to original sources
PubMed1992

Latex-based thin-layer immunoaffinity chromatography for quantitation of protein analytes.

A rapid immunochromatographic method for qualitative and quantitative analysis of protein antigens is described. The method is based on the "sandwich" assay format using monoclonal antibodies (Mabs) of two distinct specificities. Mabs of one specificity are covalently immobilized to a defined detection zone on a porous membrane while Mabs of the other specificity are covalently coupled to blue latex particles which serve as a label. The sample is mixed with the Mab-coated particles and allowed to react. The mixture is then passed along a porous membrane by capillary action past the Mabs in the detection zone, which will bind the particles which have antigen bound to their surface, giving a blue color within this detection zone with an intensity logarithmetrically proportional to the antigen concentration in the sample. Analysis is complete in less than 10 min, requires a minimum amount of sample (4 microliters), and has a detection limit below the nanomolar range for the antigen we studied, human chorionic gonadotropin.

Antibody Specificity↗
PubMed1992

A DNA polymorphism for LCAT is associated with altered LCAT activity and high density lipoprotein size distributions in baboons.

A polymorphic Pvu II site was mapped to intron 5 of LCAT, the gene encoding baboon lecithin: cholesterol acyltransferase (LCAT). In a study of 83 baboons, heterozygous baboons (Pv1/Pv2) had significantly higher LCAT enzyme activity levels than did baboons homozygous for the more common allele (Pv1/Pv1). LCAT genotype explained 6% of the total variation in LCAT enzyme activity. To test for allelic effects on cholesterol metabolism, we compared serum concentrations of high density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I). We also compared distributions of cholesterol and apo A-I among three HDL size classes (HDL1, HDL2, and HDL3). All measurements were obtained for each baboon after long-term feeding of a basal diet low in cholesterol and fat and again after 7 weeks on an atherogenic diet. Heterozygous baboons had significantly lower serum levels of total cholesterol than did homozygotes. In addition, we detected significant effects of LCAT genotype on size distributions of HDL cholesterol and apo A-I on both diets but did not detect any genotype-by-diet interaction. Heterozygotes had increased amounts of cholesterol and apo A-I in HDL3 particles and lower amounts of cholesterol and apo A-I in the larger HDL size classes by comparison with homozygotes. Overall, the LCAT polymorphism explained a significant proportion of total variation in cholesterol (4-10%) and apo A-I (13%) distributions on both diets. Thus, the results indicate that the LCAT polymorphism is associated with significant differences in LCAT enzyme activity and with alterations in HDL compositions.

Animals↗
PubMed1990

Fractionated proton radiation therapy of cranial and intracranial tumors.

Since 1973 fractionated proton radiation therapy has been used in the treatment of malignant disease. Protons have favorable physical characteristics that yield dose distributions superior to those of photons in certain clinical situations. As of December 31, 1987, 1,678 patients had been treated. Of these, 110 had chordomas or low-grade chondrosarcomas of the base of skull. The first 68 patients have a minimum follow-up of 17 months. The median dose was 69 Cobalt Gray Equivalent (CGE). (CGE is the dose in proton Gray multiplied by 1.1, which is the relative biological effectiveness for protons relative to 60Cobalt.) The actuarial 5-year local control rate is 82%, and the disease-free survival rate is 76%. Thirteen patients with meningiomas have been treated, following subtotal resection. The median dose was 59.4 CGE. With a median follow-up of 26 months, no patient has had tumor progression. In addition, nine patients with gliomas and 12 with craniopharyngiomas have been treated.

Adolescent↗
PubMed1989

Effects of a smoking ban on a general hospital psychiatric unit.

On January 1, 1987, the Board of Trustees of Southwest Washington Hospitals instituted a smoking ban in all of its facilities, including the 17-bed general psychiatry unit. Our study of ward atmosphere, PRN medications, and negative incidents related to that change are reported. We feel the change was introduced successfully with minimal impact on the successful function of our service. Others are encouraged to proceed with validation of our experience.

Adaptation, Psychological↗
PubMed1989

Conservative treatment of uveal melanoma: local recurrence after proton beam therapy.

Twenty-three of 1006 (2.3%) uveal melanoma patients treated with proton beam therapy at the Harvard Cyclotron Laboratory between July 1975 and December 31, 1986 received additional treatment for documented (15 patients) or suspected (eight patients) tumor growth in the irradiated eye. Growth within the initially irradiated volume was documented at Massachusetts Eye and Ear Infirmary in 12 patients. Documented growth occurred in nine of 665 (1.4%) patients with small and intermediate size tumors, at times after treatment ranging from 6 to 48 months (median 16 months), and in three of 341 (.9%) patients with large tumors at 7, 11, and 12 months after treatment. Melanoma growing totally outside the treated volume was also documented in three additional patients at 7, 9, and 45 months; two of these were thought to be "ring melanomas". Eight patients had the treated eye removed elsewhere for suspected tumor growth. The additional treatment in these 23 patients was conservative in nine patients (repeat proton irradiation in five and laser photocoagulation in four). Thirteen underwent immediate enucleation and one had orbital exenteration. Ultimately, 17 of the 23 eyes (74%) were removed. Estimated probability of local control of the melanoma within the irradiated eye at 60 months was 96.3 +/- 1.5%. Dose distributions to the 12 patients with documented local failure within the irradiated volume were analyzed. Ten tumors recurred marginally in an area receiving less than the prescribed dose of 70 CGE (CGE = Cobalt Gray Equivalents = proton Gy X RBE 1.1), whereas only two recurred in the volume receiving full dose. Based on these data, it appears that a dose of 70 CGE in five fractions is associated with very high rates of local control in human uveal melanoma. It is reasonable to consider initiating studies using a lower total dose or a more protracted course, to determine if some of the observed complications are dose-related.

Adult↗
PubMed1989

Neurovisual outcome following proton radiation therapy.

From February 1981 to January 1984, 20 patients with a tumor of the upper clivus received proton irradiation at the Harvard Cyclotron Laboratory. For 15 patients with known neurovisual status (including visual acuity, color vision, visual field, and fundus examinations) we obtained a cumulative dose-volume histogram (DVH) of the optic nerves (ON) and the optic chiasm. The prescribed tumor doses ranged from 66.6 to 74.4 Cobalt Gray Equivalent (CGE) with a daily fraction size of 1.8 to 2.1 CGE. CGE is used because modulated protons have an RBE of 1.1 compared to 60Co. The follow-up ranged from 30 to 68 months (median 52). Two patients developed, 10 and 36 months post irradiation, a progressive visual deterioration affecting both eyes. This was attributed to an ON and a chiasm injury in one patient and to bilateral ON injury in the other patient. In the first patient, the dose-volume analysis indicated that approximately half of the ON and of the chiasm had received 65 CGE and 55 CGE, respectively. In the second patient, it indicated that a quarter of the left ON (LON) had received 55 CGE whereas the dose to the right ON (RON) was significantly less. This patient had diabetes mellitus which may be a predisposing factor. From this study, a complication rate of 20% (1/5) is observed when a substantial portion of the ON is taken to 65 CGE, while it doesn't exceed 12.5% (2/16) and 7.5% (1/13) at 55 CGE for the ON and for the chiasm, respectively. This suggests a tolerance dose implying a 10% rate of major complications close to 55 CGE. When a tumor requires a high radiation-dose, the exclusion of these structures at 55 to 60 Gy is recommended.

Adult↗
PubMed1989

Fractionated proton radiation therapy of chordoma and low-grade chondrosarcoma of the base of the skull.

Sixty-eight patients with chordoma or low-grade chondrosarcoma at the base of the skull received fractionated high-dose postoperative radiation delivered with a 160-MeV proton beam. Protons have favorable physical characteristics which allow the delivery of high doses of radiation to these critically located tumors. The methods employed for these treatments are described. These patients have been followed for at least 17 months and for a median of 34 months. The median tumor dose was 69 CGE (cobalt Gy equivalent): CGE is the dose in proton Gy multiplied by 1.1, which is the relative biological effectiveness for protons compared to cobalt-60. The daily dose was 1.8 to 2.1 CGE. For this group the 5-year actuarial local control rate is 82% and disease-free survival rate is 76%. The incidence of treatment-related morbidity has been acceptable.

Adolescent↗
PubMed1988

Conservative treatment of uveal melanoma: probability of eye retention after proton treatment.

Enucleation was performed after proton treatment in 57 of 1006 (5.7%) uveal melanoma patients treated with proton beam therapy at the Harvard Cyclotron Laboratory between July 1975 and December 31, 1986. Only 2% of 99 patients with small tumors and 4% of 566 patients with intermediate size tumors underwent enucleation after treatment; 10% of 341 patients with large tumors lost the treated eye. No eyes were removed after 52 months, with 89% of enucleations performed during the first 36 months after treatment. Eye retention rates at 60 months were 89.1 +/- 3.0% for the entire group, and 97 +/- 3.7%, 92.7 +/- 3.1%, and 78.3 +/- 7.0% in patients with small, intermediate, and large tumors, respectively. Significantly greater enucleation rates were observed in patients with large tumors than in those with intermediate tumors (p = less than .0001), in patients with tumor height greater than 8 mm relative to those with tumors less than or equal to 8 mm, p = (less than .0001), with tumor diameter greater than 16 mm compared to less than or equal to 16 mm, (p = less than .0001), and with tumor involvement of the ciliary body compared to involvement of the choroid only (p = less than .0001). Possible strategies to decrease the likelihood of enucleation in patients at apparently increased risk of losing the eye after conservative therapy, that is, those with large tumors involving the ciliary body, might include a lower total dose, a more protracted treatment course, or a lower radiation dose and adjuvant treatment with chemotherapy and/or immunotherapy, with hyperthermia, or with other radiation sensitizers.

Actuarial Analysis↗
PubMed1988

Endocrine function following high dose proton therapy for tumors of the upper clivus.

The endocrine status of patients receiving proton radiation for tumors of the upper clivus was reviewed to evaluate the effect of high dose treatment on the pituitary gland. The fourteen patients had chordomas or low grade chondrosarcomas and were all treated by the same techniques. The median tumor dose was 69.7 Cobalt Gray Equivalent (CGE) with a range from 66.6 to 74.4 CGE. (CGE is used because modulated protons have an RBE of 1.1 compared to 60Co). The daily fraction size was 1.8-2.1 CGE. The median follow-up time is 48 months, ranging from 30 to 68 months. All treatments were planned using a computerized multi-dimensional system with the position of the pituitary outlined on the planning CT scan. Review of the dose distribution indicated that the dose to the pituitary ranged from 60.5 to 72.3 CGE, with a median of 67.6 CGE. One female patient had decreased thyroid and gonadotropin function at the time of diagnosis and has been on hormone replacement since that time. The other three females were all pre-menopausal at the time of radiotherapy. At this time four patients (3 males and 1 female) have developed endocrine abnormalities 14 to 45 months after irradiation. All four had evidence of hypothyroidism and two have also developed corticotropin deficiency. The three males had decreased testosterone levels; the female patient developed amenorrhea and hyperprolactinemia. All four are asymptomatic with ongoing hormone replacement.

Adolescent↗
PubMed1987

Combined surgery and radiation in endometrial carcinoma: an analysis of prognostic factors.

From 1969 to 1979, 300 patients with the diagnosis of endometrial cancer operated elsewhere were referred for treatment to the Department of Radiation Oncology at Memorial Sloan-Kettering Cancer Center. All the patients were staged according to FIGO classification. One hundred and seventy-three patients were Stage IA, 105 patients were Stage IB, and 22 patients were Stage II. Within Stage IA, 141 patients had well differentiated tumor (G1), 20 had moderately well differentiated tumor (G2), and 12 patients had poorly differentiated (G3). One hundred and thirty-three patients had superficial myometrial invasion and 40 patients had deep myometrial invasion. Within Stage IB, 69 patients had G1 tumor, 23 had G2, and 13 had G3 tumors. Seventy-four patients in this group had superficial myometrial invasion and 31 patients had deep myometrial invasion. Two hundred and eighty-three patients had adenocarcinoma, 13 patients had adenoacanthoma, 4 patients had adenosquamous and other histological types. All of the patients received combined surgery (total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) and radiation. The radiation treatments consisted of external pelvic radiation and intravaginal vault radiation. External pelvic radiation was delivered with a megavoltage apparatus for a total dose of 4,000 cGy in 4 weeks preoperatively (47 patients) or postoperatively (105 patients) in patients presenting with high grade (G2,G3), more than 1/3 myometrial invasion, Stage II and extrauterine extension of disease at surgery. All patients received in addition, postoperative intravaginal vault irradiation consisting of 2100 cGy in 3 fractions over 4 weeks with a high dose rate remote afterloading technique. The follow-up in these patients ranged from 5-14 years. Survival data was calculated according to Kaplan-Meier Method and Cox regression multivariate analysis to identify the prognostic factors. The 10-year survival rate in Stage IA was 91%; in Stage IB 75%; and in Stage II it was 71%. Eleven patients (4%) developed recurrent disease with either local and/or distant metastasis. Nine-percent of the patients developed mild to moderate complications which resolved with conservative treatment. Patients with gross extra-uterine pelvic extension of disease had a poor survival compared with those presenting with microscopic involvement (40% vs. 80% at 5-years). No statistically significant difference in survival was observed between patients who received either preoperative or postoperative external pelvic irradiation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1986

Automated thermometric enzyme immunoassay of human proinsulin produced by Escherichia coli.

We have determined and monitored the production and release of human proinsulin by genetically engineered Escherichia coli cells. Several M9 media samples were analyzed sequentially after centrifugation with the aid of a rapid automated flow-through thermometric enzyme-linked immunosorbent assay (TELISA) system. The response time was 7 min after sample injection and a single assay was complete after 13 min. Insulin concentrations in the range of 0.1-50 micrograms/ml could be determined. The TELISA method correlated well with conventional radioimmunoassay determinations. Standard curves were reproducible over a period of several days even when the immobilized antibody column was stored at 25 degrees C in the enzyme thermistor unit. Thus, immediate assay start up was possible.

Enzyme-Linked Immunosorbent Assay↗
PubMed1985

Antibodies to the neutral glycolipid asialo ganglio-N-tetraosylceramide: association with gynecologic cancers.

As part of our efforts to define subpopulations at increased risk for gynecologic malignancies, sera from 145 women were obtained prior to diagnosis and analyzed for antibody to asialo ganglio-N-tetraosylceramide. This neutral glycolipid is present on the surface of thymocytes and natural killer cells, and asialo ganglio-N-tetraosylceramide antibody has been shown in animals to block natural killer cell activity and promote tumor cell proliferation. With the use of an enzyme-linked immunosorbent assay and with a value of 2 SD above the mean for healthy women designated as the boundary for a positive response, antibody to asialo ganglio-N-tetraosylceramide was detected in only one of 30 (3%) healthy women, none of 16 pregnant women, none of 18 women with benign masses, and two of 24 (8%) women with microbial infections. All of the above samples that contained antibodies were barely over the 2 SD limit. In marked contrast, 19 of 35 (54%) women with gynecologic malignancies had asialo ganglio-N-tetraosylceramide antibodies, with positive values ranging to greater than 10 SD above the control mean. Asialo ganglio-N-tetraosylceramide antibody was found in six of eight (75%) patients with cervical cancer, five of eight (63%) with endometrial cancer, and seven of 15 (47%) with ovarian cancer. Of the eight patients with Stage I gynecologic cancer at any site, five (62%) had asialo ganglio-N-tetraosylceramide antibodies. Four of 22 (18%) women with Hodgkin's disease also had antibodies, with values just exceeding 2 SD above control levels. The presence of these antibodies may contribute to an impaired immune surveillance system in these women and so increase their susceptibility to malignancy.

Antibodies↗
PubMed1984

Analysis of sera from ovarian cancer patients for immune complexes.

In contrast to other malignancies, circulating immune complexes (CICS) are usually not detected by conventional assays in the sera of ovarian cancer patients. However, a polyethylene glycol (PEG) precipitation assay has been reported to detect putative CICS in ovarian cancer. To determine if CICS were indeed present, we analyzed sera from 12 women with ovarian cancer. All were negative for CICS by the Raji cell assay; 5 (42%) were positive by the PEG assay. However, the PEG precipitate did not possess characteristics of immune complexes. IgG in sera or in the precipitate sedimented in sucrose gradients solely at the same rate as 7S monomeric IgG. In addition, the precipitates were not able to activate the complement system and the four IgG subclasses were present in the same relative concentration as that found in normal serum. The results suggest that it is probably a misnomer to label the material detected in ovarian cancer sera by the PEG precipitation assay as CICS. Instead a non-immune interaction of IgG with other components, possibly membrane fragments, is probably being measured.

Antigen-Antibody Complex↗
PubMed1983

Formation of proinsulin by immobilized Bacillus subtilis.

There has been an increasing interest in the use of immobilized cells for the production of pharmaceuticals as well as for products such as high fructose syrup or ethanol. Some of these compounds are now produced on an industrial scale whereby the cells are used in a resting or growing state or in a nonviable form as natural carriers of the enzyme(s) involved in the synthesis. The advantages of immobilized cell technology should also apply to microorganisms modified by recombinant DNA techniques to produce a variety of eukaryotic proteins such as hormones. We describe here the properties of immobilized Bacillus subtilis cells carrying plasmids encoding rat proinsulin. Cell proliferation normally coupled to DNA replication is undesirable in immobilized cell systems as "clogging' of the system occurs due to cells growing outside the beads. Therefore, different ways were investigated to inhibit cell division while allowing continued protein synthesis. We found that the addition of certain antibiotics in the growth medium, such as novobiocin which inhibits DNA replication, fulfills these requirements, allowing proinsulin synthesis and excretion to take place over a period of several days.

Bacillus subtilis↗