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Biomedical subjects

M Unger

Publications and source records attributed to M Unger.

At least 55 records · Page 3Linked to original sources

Development of monoclonal antibody imaging of metastatic prostatic carcinoma.

Indium-111-labeled monoclonal antibody directed against prostate-specific antigen was injected into ten patients with known prostatic carcinoma, nine with metastatic disease. The monoclonal antibody scan was compared to the standard technetium bone scan, and both were correlated to clinical status and to 2-year follow-up. The ratio of target-to-nontarget activity and pharmacokinetics of the radiolabeled antibody were determined. Based on these findings we are hopeful that modifications of this radiolabeled antibody approach may be used for staging and may be developed as a therapeutic adjuvant.

Adenocarcinoma↗

Breast cancer imaging with mouse monoclonal antibodies.

The localization of 111In-labelled MA5 monoclonal antibody, reactive with a breast tumor associated antigen, was studied in 17 patients. MA5 was selected because 1) it reacts with greater than 95% of primary and metastatic lesions, 2) the recognized antigen is present on the cell surface in vivo and 3) MA5 gives excellent localization in human breast tumor xenografts. Each patient received 2 mg antibody labeled with 5 mCi 111In and in some cases, 3 mg or 18 mg unlabeled carrier antibody. No serious allergic reactions were noted. There was a large uptake in the liver, less significant uptake in the spleen and bone, and minimal accumulation in the bowel. Bone lesions, primary tumors, soft tissue recurrences and lung metastases larger than 3 cm diameter were imaged, while only 1 lesion smaller than 3 cm was detected. Non specific accumulation of tracer was noted at the site of a port-a-cath, in a hematoma, in fibrocystic lesions, and at sites of previous radiation treatment. Extensive fibrosis and poor vascularization characteristic of breast tumors may explain in part the limited sensitivity of the imaging.

Antibodies, Monoclonal↗

Laparoscopic laser treatment of endometriosis with the Nd:YAG sapphire probe.

Laparoscopic surgery with the Nd:YAG laser generator and a sapphire probe was performed in 43 women for relief of pain and/or infertility associated with endometriosis and in two other women for treatment of an asymptomatic adnexal enlargement. More than half of the patients had American Fertility Society endometriosis scores of stage III or IV. Results of uterosacral denervation for pain relief were excellent, and eight of 17 patients who were attempting pregnancy with follow-up for 6 months conceived. A touch technique, reduced smoke production, and delivery via a flexible fiber constitute advantages to the surgeon compared with carbon dioxide systems.

Adult↗

A monoclonal antibody recognizes a 39 kDa protein expressed in atretic granulosa cells.

A major problem in ovarian physiology is the lack of conveniently quantifiable markers of atresia. Towards this end, we identified a monoclonal antibody (anti-OA-2) that selectively recognizes granulosa cells in atretic follicles. When cryostat sections of rat ovaries were incubated with anti-OA-2, granulosa cells in atretic follicles showed intense immunofluorescent labeling. In contrast, no anti-OA-2 immunoreactivity was observed in the granulosa of the healthy follicles. The amount of anti-OA-2 binding was significantly enhanced when atresia was stimulated by treatment with human chorionic gonadotropin, testosterone, or estrogen withdrawal. The results of immunoprecipitation and Western blot analyses indicated that the OA-2 antigen is a 39 kDa protein which is actively synthesized by the granulosa during atresia. The 39 kDa protein is localized at or near the inner surface of the plasma membrane. We conclude that the anti-OA-2 monoclonal will prove useful as a convenient analytical tool to study the regulation of granulosa atresia.

Animals↗

Scintigraphy with In-111-labeled monoclonal antitumor antibodies: kinetics, biodistribution, and tumor detection.

The purpose of this study was to evaluate and compare the kinetics, biodistribution, and tumor-depicting properties of three intact indium-111-labeled murine monoclonal antibodies (MoAb) and to determine if use of In-111-labeled F(ab')2 fragments of one of them had advantages over its intact counterpart for immunoscintigraphy. Ten patients with prostate cancer were studied with an anti-prostatic acid phosphatase MoAb (PAY-276), with a resultant tumor detection rate of 15%. Twenty-eight patients with melanoma were studied with ZME-018, a MoAb that targets the KD-240 melanoma antigen. Forty-three percent of the known lesions were detected. Forty patients with carcinoembryonic antigen (CEA)-producing tumors were studied, 24 with intact ZCE-025, and anti-CEA MoAb, and 16 with its F(ab')2 fragment. With use of intact ZCE-025, 34% of known lesions were detected versus 83% with its F(ab')2 fragment. The distribution of each MoAb appears unique unto itself with regard to kinetics, normal tissue distribution, and response to MoAb mass.

Antibodies, Monoclonal↗

Radioimmunoimaging of metastatic medullary carcinoma of the thyroid gland using an indium-111-labeled monoclonal antibody to CEA.

Elevated levels of carcinoembryonic antigen (CEA) or calcitonin after surgical therapy for medullary carcinoma of the thyroid gland (MCT) indicate the presence of residual or metastatic disease. CEA elevations appear to be prognostically more reliable in patients with metastatic disease and suggest a more virulent tumor. Attempts to stage the disease with use of conventional imaging techniques are usually inadequate, as is the therapy for disseminated or recurrent MCT. An indium-111-labeled anti-CEA monoclonal antibody (ZCE-025) was used to image metastases in a patient with MCT. Potential applications of monoclonal antibody technology in the management of MCT would include (1) preoperative differentiation of unicentric from multicentric thyroid gland involvement, (2) detection of regional or distant metastases or both, (3) measurement of response to systemic therapy, and (4) the facilitation of radionuclide immunoconjugate therapy.

Antibodies, Monoclonal↗

Radioimmunodetection of human melanoma with indium-111-labeled monoclonal antibody.

The purpose of the study was threefold: (1) to evaluate the efficacy of an 111In-labeled murine monoclonal antibody (ZME-018) directed against a heavy molecular weight melanoma associated glycoprotein in localizing metastatic disease; (2) to determine the effect of unlabeled antibody mass (2.5, 5, 10, 20, and 40 mg) on labeled antibody blood clearance, biodistribution and lesion detection; (3) to estimate radiation dosimetry. Twenty-five patients with previously documented disease received an intravenous infusion of 2.5 to 40 mg of monoclonal antibody with 1 mg of the antibody labeled with 5 mCi of 111In. There were no acute reactions. Patients were scanned without computer enhancement or background subtraction techniques at 24 and 72 hr after injection. Imaging detected tumor in 14/18 (78%) patients with active disease, identified 24/44 (77%) of lesions greater than 1 cm and changed or specifically directed patient management in 22% (4/18) patients with tumor. There was a prolongation in blood clearance associated with decreased liver and spleen activity following administration of 20 and 40 mg of antibody compared to the three lower antibody dose levels. Assuming a biodistribution similar to [111In]ZME-018, the radiation dose delivered to normal tissues by [90Y]ZME-018 would restrict its use as a routine vehicle for radioimmunotherapy; however, it may be possible to deliver substantial tumor doses in selected patients.

Adult↗

Enhancing CEOs' decision making through information systems.

Although healthcare management information systems significantly enhance the decision-making capacity of the chief executive officer (CEO), some CEOs make limited use of this potentially powerful management ally. A central management issue is finding the optimal fit between the CEO's roles and responsibilities and the capacity of information systems to adapt to and support these functions. Thus data system designers must clearly understand the CEO's needs, management tasks, and unique responsibilities. An often misunderstood concept is that data by themselves are not immediately useful and applicable to managerial needs. To become useful information, data must be timely, accurate, relevant, and actionable. CEOs may be disappointed with management information systems because of an inherent conflict between what the computer can do best--rapid, routinized solutions--and what top management usually requires. The CEO's decisions are generally singular, and the system's data may not be structured to serve those decision-making requirements. Building a system that is responsive to the CEO's needs requires an equal partnership between the CEO, data manager, and system designer. The CEO also must be willing to invest a lot of time in shaping the facility's system. In addition, because of the considerable and escalating cost of developing, using, and maintaining organizational data systems, CEOs must assess the cost/benefit ratio of obtaining additional information from existing data bases.

Computer Systems↗

Should health care managers adopt Theory Z?

Health care administrators should carefully consider the situations in which they apply management methods used in industry, since such methods may not be effective in motivating certain groups of hospital employees. Physicians, for example, may display little loyalty to the health care organization, even though as a group they exert significant influence on policies, standards, and administration. As a result, management styles such as Theory Z that focus on holistic concern, individual decision-making responsibility, and long-term employment guarantees may fail to interest them. Nurses also may be reluctant to commit themselves to an organization because of the high rate of turnover in their profession in recent years. Support staff, however, probably would be receptive to management techniques that offer security through long-term employment guarantees. Other factors necessary for the effective use of Theory Z industrial management techniques are a clear hierarchy with well-defined reporting relationships, moderately specialized career paths, and trust among employees that the organization's concern for their welfare is genuine. The key consideration, however, in applying any theory is that only those aspects which best serve the organization's needs should be adopted.

Catholicism↗

General anaesthesia for Nd:YAG laser resection of obstructing endobronchial tumours using the rigid bronchoscope.

Provision of general anaesthesia for patients undergoing Nd:YAG laser resection of obstructing endobronchial tumours using the rigid bronchoscope presents unique problems for the anaesthesiologist. We studied 15 patients who underwent 20 of these procedures under general anaesthesia. Patients were anaesthetized and ventilated with either potent inhalation agents via the side arm of the ventilating bronchoscope (Group I: N = 8), or with intravenous agents and the Sanders jet injector attached to the rigid bronchoscope (Group II: N = 12). Patients were paralyzed and ventilation was controlled. The inspired gas mixture was nitrogen and oxygen, and the FIO2 was decreased to 0.3-0.4 during periods of resection. Group I patients had significantly higher peak pCO2's than Group II (8.3 kPa (62 mmHg) vs. 5.6 kPa (44 mmHg); lowest recorded pO2's were comparable and similar to pre-induction values. Both groups exhibited wide blood pressure fluctuations. Heart rates remained within 15 per cent of pre-induction levels. There were no intraoperative deaths, and no airway fires, massive haemorrhages or pneumothoraces. We conclude that these procedures can be undertaken with the use of general anaesthesia and the rigid bronchoscope, but that patients may encounter potentially serious respiratory or haemodynamic instability during the procedure.

Aged↗

Effects of liver damage induced by polychlorinated biphenyls (PCB) on cadmium metabolism in mice.

Polychlorinated biphenyls (PCB) were added to the diets of mice at different concentrations. Mice fed these diets were given a sc or oral doses of 109Cd. The uptake and excretion of Cd was followed by whole-body counting. The gastrointestinal absorption of Cd after an oral dose of 109Cd was less in animals fed on 66 ppm PCB diet, compared with a control group, and the body elimination of Cd was faster. In the liver, the amount of Cd was reduced by dietary PCB exposure, after both oral and sc administration of 109Cd, and the data suggest a faster transport of Cd from liver to kidneys in PCB-exposed animals than in controls. The mobilized liver Cd was not quantitatively recovered in the kidneys, thus increased urinary excretion due to PCB exposure may have taken place. Histological examination of the livers revealed a dose-dependent induction of liver changes characterized by centrilobular enlargement of liver cells and centrilobular focal necroses. In four of eight livers from animals fed 200 ppm PCB for 32 weeks there were five liver cell tumors with cytological signs of malignancy. In the control group and in groups fed lower doses of PCB (10-100 ppm) no such tumors were found among 28 animals. The results support observations made with agents inducing acute liver damage, that liver damage increases the rate of redistribution of cadmium from the liver to the kidney.

Animals↗

Characterization of DNA and RNA in circulating immunocomplexes in multiple sclerosis, amyotrophic lateral sclerosis and normal controls.

The total levels of DNA and RNA in serum immunocomplexes from multiple sclerosis (MS) patients and healthy control persons were compared. Furthermore, the levels of single-stranded DNA (ss DNA) and double-stranded DNA (ds DNA) in serum immunocomplexes from MS patients, amyotrophic lateral sclerosis (ALS) patients and controls were studied. The mean values of DNA and RNA were found to be elevated (P less than 0.01) in MS compared to the control means. Furthermore, the RNA/DNA ratio and the ratio ss DNA/ds DNA were decreased in MS. In contrast the ss:ds DNA ratio in ALS was increased. In ALS, however, the sum of ss DNA and ds DNA was lower (P less than 0.05) than the control mean value.

Adult↗

A monoclonal antibody to a mammary cell line recognizes two distinct subtypes of ovarian granulosa cells.

When screening supernatant fluids from hybridoma clones, Dulbecco and co-workers found that a mouse monoclonal antibody generated against a mammary tumor cell line showed rather striking high binding to rat oocytes and granulosa cells. In this study we have specifically investigated the reactivity of the monoclonal antibody (designated anti-OA-1) with granulosa cells during the differentiation process. This was accomplished using the two-step indirect immunocytochemical technique. When a primordial follicle is recruited to initiate growth, intense immunoreactivity appears in the surface membrane of the granulosa cells. As a follicle proceeds through the preantral stages, the plasma membrane of the granulosa cells is strongly positive for anti-OA-1 reactivity, and the granulosa appear as a homogeneous population. However, once Graafian follicle development is initiated, a major shift in anti-OA-1 immunoreactivity occurs among the granulosa cells. As the antrum expands, 75% of the granulosa in the mural region (those nearest the basal lamina) elongate and become negative for anti-OA-1. This is in contrast to the periantral and cumulus granulosa, which remain rounded and show strong anti-OA-1 reactivity up to the preovulatory stage. The disappearance of anti-OA-1 reactivity in the subpopulation of mural cells is specifically initiated by FSH and occurs very rapidly after a 12-h lag phase. After the loss of anti-OA-1 reactivity, the elongated mural granulosa cells express their terminal differentiated state by acquiring LH/hCG receptor, 3 beta-hydroxysteroid dehydrogenase activity and cytoplasmic lipid inclusions. By contrast, the periantral and cumulus granulosa, which remain positive for anti-OA-1, do not express these differentiated functions; however, they do differentiate ultrastructurally, indicating that they respond to the FSH signal. These results strongly suggest that a monoclonal antibody recognizes a major surface differentiation antigen in the granulosa cell. This antigen is under hormonal control and is inversely linked to expression of the terminal differentiation program in the granulosa cells. We anticipate that the monoclonal antibody will be a valuable probe to aide in the analysis of structure/function relationships in subpopulations of granulosa cells.

Animals↗

Neodymium:YAG laser therapy for malignant and benign endobronchial obstructions.

Because of its specific wavelength (1064 nm), the Nd:YAG laser can be transmitted through fiberoptics and has very specific characteristics of a high-scattering effect in living tissues, permitting in-depth penetration of energy and coagulation of cellular protein. Among other topics, this article reviews the indications for and complications of endoscopic Nd:YAG therapy.

Bronchoscopes↗