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Biomedical subjects

P Witt

Publications and source records attributed to P Witt.

13 recordsLinked to original sources

Quantitation of interferon-induced Mx protein in whole blood lysates by an immunochemiluminescent assay: elimination of protease activity of cell lysates in toto.

Due to the rapidly expanding usage of interferons and its costliness of therapy, it is important to evaluate the clinical efficacy of the various interferons. Directly assaying circulating interferon is technically quite difficult. Here, we present an alternate method to evaluate interferon therapy by assaying a unique protein, called Mx protein, which is a 78 kDa cytoplasmic protein selectively induced by type-1 interferon in human leukocytes. The current assay is a two-site chemiluminescent immunoassay, designed to detect Mx protein in whole blood lysates. Since the Mx protein once solubilized, is highly susceptible to proteolysis in whole blood lysates, we have devised a new procedure both to maximize its solubility and virtually eliminate its proteolytic degradation. A mouse monoclonal antibody conjugated to the derivatized-paramagnetic particles and an acridinium ester-labeled antibody serve as the solid phase capture and detector antibodies, respectively. This assay is applicable to both manual and automated modes with a detection limit of Mx protein at 20 ng/ml whole blood. Availability of a reliable assay for Mx protein should facilitate the clinical evaluation of many of the newly constructed type-1 interferons.

Animals

Evidence for the elevation of serum carcinoembryonic antigen and tumor-associated glycoprotein-72 levels in patients administered interferons.

Sera were collected from 111 patients diagnosed with adenocarcinoma or nonadenocarcinoma malignancies who received different schedules of interferon (IFN)-gamma or IFN-beta ser alone or in combination. Serum carcinoembryonic antigen (CEA) and tumor-associated glycoprotein-72 (TAG-72) antigen levels were measured to determine whether interferon could enhance the tumor shedding and, thereby, the serum level of either tumor antigen. Less than 10% of the sera samples from patients diagnosed with nonadenocarcinoma malignancies (e.g., hairy cell leukemia, melanoma) had positive titers of TAG-72 or CEA, and interferon neither increased nor resulted in the appearance of either tumor antigen in those sera. In contrast, 59.2% and 75.4% of the patients with adenocarcinoma had positive serum levels of TAG-72 and CEA, respectively, prior to interferon. IFN-gamma and IFN-beta ser alone or in combination significantly increased serum TAG-72 or CEA in approximately 65% of those patients. The results suggest that interferon administration to patients with adenocarcinoma can result in increased serum levels of selected tumor-associated antigens used in the diagnosis of malignancy. These preliminary findings may be important in the development of new strategies to obtain more sensitive tumor antigen serum assays for the diagnosis and monitoring for disease progression of adenocarcinoma.

Adenocarcinoma

Transfer dysphagia in a patient with the rare combination of scleroderma and ankylosing spondylitis.

Esophageal involvement in scleroderma is generally confined to the body, manifested manometrically as impaired motility and decreased lower esophageal sphincter tone. Pharyngeal dysfunction has not been recognized. This is a report of a patient with the rare combination of scleroderma and ankylosing spondylitis, whose presenting complaint was transfer dysphagia due to impaired relaxation of the upper esophageal spincter as a result of tight overlying cervical skin, or sclerodermatous involvement of the sphincter itself.

Deglutition Disorders

Nifedipine therapy for diffuse esophageal spasm.

Although nifedipine therapy resulted in substantial relief of dysphagia in six patients with diffuse esophageal spasm, significant side effects, particularly in young working subjects, precluded prolonged use.

Dizziness

Experimental hyperextension supracondylar fractures in monkeys.

Discarded monkey autopsy specimens were used to investigate the mechanism of supracondylar hyperextension fracture. As the fracture progressed from mild angulation to complete lateral or medial displacement, the anterior periosteum first was detached from the bone and then stripped distally before tearing over the edge of the proximal fragment. Stability or reduction by acute elbow flexion and forearm pronation, owing to compressive forces, was transmitted through the elbow joint on the medial side of the fracture, and stability was not significantly influenced by a bridging periosteal hinge or forearm musculature. Forearm supination and elbow flexion of less than 90 degrees resulted in less stability. The influence of acute elbow flexion and forearm pronation was diminished when the fracture was distracted by traction. Interposition of the anterior periosteum in displacement fractures prevented anatomic reduction.

Age Factors