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Biomedical subjects

A S Cohen

Publications and source records attributed to A S Cohen.

At least 19 recordsLinked to original sources

Serum amyloid A protein in amyloidosis, rheumatic, and enoplastic diseases.

Serum levels of amyloid protein A (SAA) have been shown to be elevated in different types of amyloidosis and in rheumatic diseases by radioimmunoassay using 125 iodine labeled AA and anti-AA. SAA levels were elevated in both primary and secondary amyloidosis, but there were highly significant differences between these levels. In heredofamilial amyloid, SAA levels were within normal limits. While the mean SAA level was elevated in persons over 70 years, the fact that some persons in this age group had normal levels suggested that marked elevation after age 70 may be due to occult inflammatory or neoplastic disease. High SAA levels in patients with rheumatoid arthritis correlated, in most cases, with physician evaluation of disease activity and Westergren ESR. SAA levels in patients with systemic lupus erythematosus were lower than those in patients with rheumatoid arthritis, and most patients with degenerative joint disease had normal levels. Very high levels of SAA were found in patients with neoplastic diseases. Patients with carcinoma of the lung and bowel had much higher levels than patients with carcinoma of the breast. Determination of SAA levels may be of value in evaluating different forms of systemic amyloidosis, assessing the activity of rheumatic disease, and screening for occult inflammatory or neoplastic disease.

Aged

A review of the use, evaluations, and criticisms of the preliminary criteria for the classification of systemic lupus erythematosus.

The use of the Preliminary Criteria for the Classification of Systemic Lupus Erythematosus (SLE) has been reviewed. Most authors describing 10 or more patients have used the criteria. Although originally designed for classification of patients, the criteria have often been used for the diagnosis of SLE. The sensitivity of the criteria was evaluated and found to be similar to the 90% reported in the original ARA trial. Studies on specificity yielded conflicting results. Various suggestions to improve the criteria have been made, including a more detailed description of some of the organ involvements and the adoption of laboratory tests that have been improved since or were unavailable at the time of original publication of the criteria.

Antibodies, Antinuclear

The effect of a primary-care pathway on internal medicine residents' career plans.

There has been no evidence that primary-care pathways, a recent innovation in internal medicine residency programs, have affected the career choices of their trainees. We report the experience of the first four cohorts of primary-care trainees in internal medicine compared with traditional-pathway trainees at Boston City Hospital. Primary-care residents remained committed to their plans for a career in general internal medicine throughout training. In contrast, two thirds of the traditionally trained residents who were planning a career in general internal medicine at the beginning of their training changed their plans to subspecialty medicine. Thus, the primary-care pathway reinforced the career plans of trainees in general internal medicine, whereas traditional training influenced potential generalists toward subspecialty medicine.

Boston

Binding of serum amyloid P-component (SAP) by amyloid fibrils.

Serum amyloid P-component (protein SAP) was found to bind in vitro to isolated amyloid fibrils of both primary and secondary types. The binding was strictly calcium-dependent, optimal uptake requiring at least 0.5 mM calcium ion. Using normal human serum as the source of protein SAP different fibril preparations became saturated with between 5--20 micrograms of SAP per mg dry weight of fibril. Isolated pure protein SAP bound in greater amounts. In control experiments SAP did not bind significantly to collagen fibrils, sheep erythrocytes, plastic shavings, or the following immobilized proteins: human kappa or lambda Bence-Jones proteins; human; rabbit or mouse IgG; human serum albumin. C-reactive protein, which resembles protein SAP structurally but has calcium-dependent specificity for different ligands, bound significantly to only one of five different amyloid fibril preparations.

Amyloid

Serum amyloid P-component levels in amyloidosis, connective tissue diseases, infection, and malignancy as compared to normal serum.

A highly sensitive radioimmunoassay was developed to measure the serum levels of SAP. Sera from 50 normal individuals ranging in age from 4 to 89 years had a mean level of 7.47 mg/dl and showed no variations with age. Sera from persons with various clinical types of amyloidosis, connective tissue diseases, and bacterial pneumonia did not differ significantly from normal values. A significant difference was noted in the sera from persons with malignancy, where a mean value of 10.79 mg/dl was determined. Although a number of similarities exist between SAP and CRP, SAP does not share the property of being an acute-phase reactant.

Adolescent

The rheumatologic manifestations of diabetes mellitus.

The rheumatologic disorders associated with diabetes mellitus have been reviewed. From the evidence presented, it can be concluded that neuroarthropathy and osteolysis are definitely assoicated with diabetes. Ankylosing hyperostosis and periarthritis probably represent valid associations, and possible, but still unproven associations exist for gout, pseudogout, the carpal tunnel syndrome, osteoarthritis, Dupuytren's contracture and joint contractures. Despite the lack of a proven pathophysiologic basis these interrelationships may be clinically relevant. The discovery of one of these disorders may provide a clue to underlying glucose intolerance, and idabetics should be followed with the knowledge that they are at risk for the development of certain musculoskeletal problems.

Ankylosis

Synovial membrane histopathology in the differential diagnosis of rheumatoid arthritis, gout, pseudogout, systemic lupus erythematosus, infectious arthritis and degenerative joint disease.

The synovial membrane histologic sections from patients with six common rheumatic diseases were reviewed without knowledge of the clinical diagnosis. After histopathologic evaluation, the synovial membrane characteristics were grouped according to the patient's clinical diagnosis, and included 29 patients with rheumatoid arthritis, 13 with systemic lupus erythematosus, 17 with degenerative joint disease, 10 with acute bacterial arthritis, 8 with gout, and 13 with pseudogout. The only specific characteristics identified were bacteria (infectious arthritis), crystals (gout, pseudogout), and lymphoid follicles (rheumatoid arthritis). Nevertheless, other characteristic features of differential diagnostic utility were recognized, including the intensity and nature of synovial lining cell hyperplasia and of leukocyte infiltration. Light microscopic histopathologic changes in the common rheumatic diseases are not specific, but are of diagnostic utility. Complete and exhaustive review of each pathologic synovial membrane characteristic provides more justification for the routine use of synovial membrane biopsy as an adjunct to arthrocentesis in the evaluation of common rheumatic diseases.

Arthritis

Localized amyloidosis of the lower respiratory tract.

Amyloidosis limited to the lower respiratory tract is a relatively rare condition. Three new patients are reported, and the pertinent literature is reviewed. The available information is discussed with regard to clinical forms, diagnostic methods, therapy, and clinical course. Tracheobronchial deposition is the most frequent form of localized amyloidosis; it affects relatively younger persons and often gives rise to symptoms of airway obstruction. Bronchoscopy, although carrying a risk of bleeding, is the procedure of choice diagnostically and therapeutically. Single or multiple pulmonary nodules are usually discovered as an incidental roentgenographic finding, and surgical resection (for suspected malignancy) has resulted in cure in all cases. On rare occasions, amyloid may be deposited diffusely in the pulmonary parenchyma, leading to death from respiratory insufficiency.

Adrenal Cortex Hormones

Patterns of pulmonary involvement in systemic amyloidosis.

The clinical and histopathologic features of pulmonary amyloidosis were reviewed in 22 patients with systemic amyloidosis who came to autopsy. Eleven of 12 patients (92 percent) with primary amyloidosis had prominent interalveolar amyloid deposits. Symptoms attributable to these deposits were found in four cases (33 percent), while severe lung involvement was the apparent cause of death in one. Extensive deposition was noted in all three cases of amyloidosis associated with multiple myeloma or Waldenstrom's macroglobulinemia. Five of seven patients (71 percent) with secondary amyloidosis showed histologic lung involvement, which was perivascular or tracheobronchial in location, but not associated with symptoms. Histologic lung involvement is frequent in all forms of amyloidosis and lung tissue obtained from any patient with unexplained interstitial or reticular-alveolar pulmonary disease should be stained with Congo-red and viewed for green birefringence under polarizing microscopy for the presence of amyloid.

Adult

Skin involvement in generalized amyloidosis. A study of clinically involved and uninvolved skin in 50 patients with primary and secondary amyloidosis.

A punch or excisional biopsy of the skin was done in 50 patients with generalized amyloidosis: In 46, clinically normal skin, usually the forearm, was biopsied and in four, only cutaneous lesions. Amyloid was seen in the skin of 21 of 38 patients with primary and multiple myeloma-associated amyloidosis. Sixteen of 34 biopsies from clinically uninvolved skin were positive. Five of 12 patients with secondary amyloidosis had amyloid deposits in clinically normal skin. Overall, amyloidosis was definitively diagnosed on skin biopsy examination in 26 patients. A punch biopsy of clinically involved or uninvolved skin is an innocuous, simple procedure with a high diagnostic yield and can be done in an office setting.

Amyloidosis

The identification of amyloid P-component (protein AP) in normal cultured human fibroblasts.

The amyloid protein, AP, has not previously been detected in normal or nonamyloidotic tissues. In this study, human fibroblasts were examined for the presence of AP by immunofluorescence technique. Normal human skin fibroblasts were cultured in Eagle's minimum essential medium for varying periods of time. Antiserum was prepared in rabbits using AP isolated from amyloid-rich tissues. Using indirect immunofluorescence and anti-AP, fluorescent material was found to be distributed in a punctate pattern throughout the cytoplasm with sparing of the nucleus. The fluorescent reaction was speicifically inhibited by absorption of anti-AP with AP-positive serum but not by addition of AP-negative human cord serum. Thus, AP may have a fibroblast origin and a relationship to normal connective tissue.

Amyloid

Fractionation of primary amyloid fibrils. Characterization and chemical interaction of the subunits.

Amyloid fibrils of kappa origin from a patient with primary amyloidosis are dissociated in various denaturants and fractionated into their subunit components on Sepharose 6B. Solubilization of the fibrils in 4 M guanidine-HCl followed by reduction and alkylation produced 22 000 and 17 000 dalton fractions. Without prior reduction and alkylation, these fractions exist as a high molecular weight protein which can be separated on Sepharose 6B. A high molecular weight protein can be directly dissociated from the amyloid fibril with 1% sodium dodecyl sulfate or 1 M NaCl. Reduction and alkylation of this material produces the two lower molecular weight fractions, i.e., 22 000 and 17 000. These have in the first 20 residues identical N-terminal amino acid sequences; they share immunologic identity and have similar tryptic peptide map profiles. Amino acid analysis of the 22 000 dalton fraction is identical with the intact immunoglobulin light chain isolated from the patient's serum. These data suggest that the insoluble amyloid fibril is the result of aggregation by disulfide linkages between the 22 000 and 17 000 dalton fractions.

Amino Acid Sequence

Movements while driving cars around curves.

The eye fixations of 5 experienced and 4 inexperienced car drivers were analyzed while driving curves to the left and to the right. For experienced drivers in a curve to the left the mean duration of eye fixations was longer and the amplitude of the eye movements greater than in a curve to the right. No such difference was observed in inexperienced drivers who manifested neither uniformity within the same curves nor differentiation between the two types of curves. Mean duration of eye fixations of experienced subjects was shorter while driving in a curve to right, but their amplitude of eye movement was greater in a curve to left than those of inexperienced drivers. In Esp. 2, it was pointed out that there is already a change in the pattern of eye movements prior to entering a curve. Upon approaching the curve the mean duration of eye fixation decreased, and the fixations were mainly shifted toward the future driving path. Results are interpreted in terms of the adequacy of the eye fixations (supposedly influenced by prior long-term learning) for information at near distance for vehicle control and at longer distances for setting proprioceptive forward programs for possible future sensomotoric activity.

Adult