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Biomedical subjects

M Tannenbaum

Publications and source records attributed to M Tannenbaum.

At least 37 records · Page 2Linked to original sources

Human hybridoma lupus anticoagulants distinguish between lamellar and hexagonal phase lipid systems.

Antibodies to phospholipids may have important physiological and biological functions. Lupus anticoagulants represent a subclass of anti-phospholipid antibodies which are characterized by their ability to prolong the clotting time in in vitro coagulation assays measuring partial thromboplastin time (PTT) (Thiagarajan, P., Shapiro, S. S., and DeMarco, L. (1980) J. Clin. Invest. 66, 397-405). In the present study, we produced hybridomas by fusing lymphocytes from 13 systemic lupus erythematosus patients with the GM 4672 lymphoblastoid line. Of the resulting 67 hybridoma autoantibodies, 14 (21%) were found to prolong a modified PTT assay, and 11 of these antibodies were analyzed further. Competition experiments, using a modified PTT assay, demonstrated that hexagonal phase phospholipids, including natural and synthetic forms of phosphatidylethanolamine, were able to neutralize the lupus anticoagulant activity of all 11 hybridoma antibodies. In contrast, lamellar phospholipids, such as phosphatidylcholine and synthetic lamellar forms of phosphatidylethanolamine, had no effect on the anticoagulant activity. Thus, these antibodies are capable of recognizing phospholipids on purely structural criteria. The demonstration that anti-phospholipid antibodies are able to distinguish between different structural arrangements of phospholipid may have important implications regarding the immunoregulation of autoimmunity.

Antibodies↗

Carcinoma of prostate metastatic to penis.

A case report of prostatic carcinoma metastasizing to the penis is presented. Review of the literature revealed only 54 cases reported to date. With survival rates ranging from two to six months, the prognosis is gloomy. The most commonly used method of treatment was local wide excision of the lesion.

Acid Phosphatase↗

Primary transitional cell carcinoma of prostatic periurethral ducts.

Primary transitional cell carcinoma of the prostatic periurethral ducts is a distinct histologic variety of prostate carcinoma. Traditional methods of therapy for adenocarcinoma of the prostate are ineffective. A review of the literature suggests that appropriate radical surgical therapy should be considered for early control of this disease.

Adenocarcinoma↗

Acid phosphatase localization in prostatic carcinoma. A comparison of monoclonal antibody to heteroantisera.

A series of 39 prostatic carcinomas was characterized in terms of grade, stage, histologic pattern, and serum acid phosphatase values. These cases were studied immunohistochemically with two different heteroantisera, a goat and rabbit antiserum, and with a monoclonal antibody to prostatic acid phosphatase (PAP). Eighty-three percent of carcinomas had some degree of PAP positivity when stained by the goat anti-PAP. Seventy percent were positive with the rabbit antiserum, and 59% showed positivity with the monoclonal antibody. Microacinar patterns were consistently the most positive for PAP, followed by cribriform patterns. The least positivity was observed in the undifferentiated, single-file and sheet-like patterns. Likewise, there was more PAP positivity in the lower Gleason and Mostofi grades. When the serum PAP positivity (done by counterimmunoelectrophoresis [CIEP]) was compared with tissue positivity (using the same goat antiserum), 37% were positive in both serum and tissue; 48% were negative in serum, but positive in tissue; and in only 9% the tissue sample was negative when the serum was positive. Based on these data, conclusions are drawn about the significance of the serum acid phosphatase elevations and the role of monoclonal antibodies and heteroantisera in clinical-diagnostic and research work.

Acid Phosphatase↗

Interaction of ultrasonic hyperthermia with two alkylating agents in a murine bladder tumor.

Fischer rats bearing s.c. implants of TCT-4909 bladder tumor were treated either with ultrasonic hyperthermia (US) (44.2 degrees, 20 min) or either of two alkylating agents, thiotepa or Cytoxan (CTX) or in combinations of chemotherapeutic agent and heat at specific time intervals. Applying US 20 hr before either agent (thiotepa, 2 mg/kg i.p.; or CTX, 50 mg/kg i.p.) had a less than additive effect upon tumor growth. CTX, administered 20 hr before US, resulted in a significantly increased tumor volume-doubling time compared to CTX only. This was not true for thiotepa. With both agents, a synergistic effect was obtained when US and the agent were applied within 1 hr of each other, but the maximum was observed when the US had been applied 30 min before injection of agent. The intratumor temperature had decayed to normal at the time of injection. Radiolabeled alkylating agents injected at different times after US showed decreased uptake of label up to 20 hr after heating. Tritiated thymidine uptake was also reduced over the same period. Nuclear morphometry indicated increased nuclear condensation in parallel with the reduced uptakes described above. The data suggest that the synergism was not due to increased uptake of agent into heated tissue nor to the direct activation of alkylating activity by heat. It was demonstrated that heat had a rapid and marked inhibitory action upon DNA synthesis. This could have augmented the delayed but prolonged DNA inhibition caused by the alkylating agents to produce a synergistic effect. The apparent prolongation of the growth-inhibitory effect of CTX or thiotepa by heat may be due to the thermal inhibition of the enzymes responsible for the recovery of DNA after alkylation. The precise mechanism for the synergy may vary with the agent, the dose, the equilibrium temperature and its dwell time, and the interval between modalities. The influence of each of these parameters will require further investigation.

Animals↗

Prostate cancer grading: light and electron microscopy.

An attempt has been made to use various morphological patterns as predictors of the pathobiology of clinically active prostate cancer. At the present time, the most predictable and time-tested procedure is that of the Gleason grading and subsequent score results. Even though there may be some deficiencies, it is the best that is currently available to the surgical pathologist and urologist. All other morphological procedures can be additive to the Gleason grading system.

Acid Phosphatase↗

Chemosensitivity of murine renal carcinoma.

A non-endocrine dependent, spontaneous carcinoma of the kidney in a Wistar-Lewis rat has been studied for sensitivity to chemotherapeutic agents. Two tumour models have been employed. Subcutaneously transplanted flank nodules were used to screen single agents for antitumour activity.. A model of intraperitoneal metastatic disease was employed to test further agents which had demonstrated some effectiveness in the nodule model. Single agents that proved ineffective were streptozotocin, neocarzinostatin, chlorozotocin and carminomycin. 5-FU, bleomycin and hydroxyurea were also ineffective at the doses tested. Agents that were effective included cyclophosphamide, adriamycin, vinblastine, vindesin and maytansine. The most effective combination therapy appeared to be cyclophosphamide with vindesin and cisplatin.

Adenocarcinoma↗

Characterization of rat colonic cell surface glycoconjugates by fluoresceinated lectins. I. Importance of fixation techniques.

Cryostat and paraffin embedded sections from cecum, proximal and distal colonic segments of male Sherman rats were examined by fluorescence microscopy after labeling with six fluorescein-conjugated lectins. These FITC-conjugated lectins were used as specific probes to define the labeling pattern of carbohydrate containing components of the lumenal and basolateral surfaces of epithelial cells, goblet cell mucin and lumenal mucin at all three sites. Marked regional differences in labeling were detected, indicating that the various carbohydrate components of these cells differ significantly along the length of the colon. Furthermore, the patterns of labeling components with each lectin appeared to vary depending on the fixation technique employed. Cryostat preparations generally resulted in a broader distribution of label and more intense staining with these lectins than fixed paraffin sections. While the reason(s) for these variations remain unclear at this time and will require further studies, the present data emphasize the importance of the fixation method when interpreting results obtained utilizing FITC-conjugated lectins.

Animals↗

Prognostic significance of nucleolar surface area in prostate cancer.

In an effort to define ultrastructural histologic features that might serve as predictors of tumor aggressiveness, a retrospective study was conducted on 52 patients with localized and metastatic adenocarcinomas of the prostate. Nucleolar surface area measurements were made by stereologically analyzing pictures obtained by the backscattered electron imaging (BEI) attachment to a scanning electron microscope (SEM). The data were compared with the Gleason grading system which is based on light microscopic glandular patterns. In patients with no evidence of disease three years or more after radical prostatectomy, the initial biopsy demonstrated nucleolar surface areas which averaged 1.28 micrometers2 (range 0.60 to 2.27 micrometers2) whereas, patients with metastases or dying of cancer exhibited an average nucleolar surface area of 5.17 micrometers2 (range 2.49 to 10.01 micrometers2). With a single exception in this 52-patient survey, progressive disease was always accompanied by nucleolar surface measurements larger than 2.40 micrometers2. There was close correlation in nucleolar surface measurements between the initial biopsy and the radical prostatectomy specimens; in contrast, Gleason grades varied by more than 30 per cent between the initial and final specimens in 70 per cent of the cases. Only 9 of 16 patients with aggressive disease ever demonstrated Gleason grades above 6. The development of an ultrastructural grading system may provide a means of determining prognosis in prostatic cancer in objectivity and specificity to light microscopic grading systems.

Adenocarcinoma↗

Counterimmunoelectrophoretic studies of serum prostatic acid phosphatase.

A counterimmunoelectrophoretic (CIEP) assay for the specific determination of prostatic acid phosphatase (PAP) is described. PAP was obtained from benign human prostatic tissue and a specific antiserum to this enzyme was produced in rabbits and goats. The lowest detectable activity of PAP was at 0.3 IU/l or 4 ng./0.1 ml. This CIEP method was compared to a standard biochemical method (Roy) on a wide spectrum of prostatic and nonprostatic disease. Nonprostatic malignancies and other disorders associated with hyperacidphosphatasemia by the biochemical method were found to be nonreactive for PAP by CIEP. Patients under treatment with various stages of prostatic carcinoma showed comparable elevations by both methods (35%). In untreated patients, the CIEP was statistically most sensitive in stage A (39% by CIEP and 14% by chemical).

Acid Phosphatase↗

Bone marrow acid phosphatase in prostate cancer: an assessment by immunoassay and biochemical methods.

Comparisons of the bone marrow and serum acid phosphatase values obtained by counter-immunelectrophoresis and the Roy biochemical test were made in 72 patients with and in 13 patients without prostatic cancer. The counter-immunoelectophoresis test, when positive at more than 1 international unit per liter, showed only 4.4 per cent falsely positive results. The Roy biochemical test, which used sodium thymolphthalein monophosphate as the substrate, had 65 per cent falsely positive bone marrow acid phosphatase levels. Conflicting reports regarding the value of bone marrow acid phosphatase determinations in patients with prostatic cancer result from the use of non-specific substrates in biochemical methods for measurement and from the trauma incidental to bone marrow aspiration, which releases many non-prostatic acid phosphatase enzymes. The use of immunoassay such as counter-immunoelectrophoresis minimizes this source of error.

Acid Phosphatase↗