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Two dissimilar U.S. medical schools--the University of Pittsburgh School of Medicine and the University of Texas Medical Branch at Galveston-changed their curricula for the first two years of medical education from ones that were lecture-dominated and departmentally run to ones that are centrally governed, multi-modal, goal-oriented, and fully integrated, with mechanisms to continue curricular change into the last two years of medical education. The change at each school was in response to national education philosophy, the recommendations of the Liaison Committee for Medical Education after the most recent site visit, and faculty's and students' concerns and interests. The change process took place over a three- to four-year period at each school, involved students, faculty, and administration, and utilized task forces and retreats as communication vehicles. The barriers encountered (e.g., belief by some that the curriculum needed no change; concern over loss of departments' control) and the processes employed to overcome them and to radically change the curricula (e.g., commitment of the central administration and dean to the change, involvement of all segments of the school in the change process, appointment of department chairs on task forces, and creation of a strong curriculum committee that gave authority to faculty and students) were essentially identical. The resulting curricula were also largely similar in their main characteristics, but there were notable differences, based on the goals and concerns of the two institutions.

The confluence of enhanced attention to primary care and palliative care education presents educators with an opportunity to improve both (as well as patient care) through integrated teaching. Improvements in palliative care education will have benefits for dying patients and their families, but will also extend to the care of many other primary care patients, including geriatric patients and those with chronic illnesses, who make up a large proportion of the adult primary care population. In addition, caring for the dying, and teaching others to carry out this task, can be an important vehicle for personal and professional growth and development for both students and their teachers.

This article describes a novel course that was designed to bridge the gap between the basic science years and clinical experiences in medical school by using information science and computer technology as major components of problem-based learning (PBL) sessions. The course, Integrated Case Studies and Medical Decision Making, was first given to second-year students at the University of Pittsburgh School of Medicine in the spring of 1994. It consists of 13 PBL exercises, each of which explores a clinical case. The cases, including images and gated access to information, are housed on a computer. Using one of 16 networked terminals in specially designed small-group rooms, groups of nine students progress through the cases with a faculty facilitator. The responses of students and faculty to the initial year of the course were favorable. In comparison with traditional PBL sessions, enhanced quality of and access to images and accountability for accessing case information in sequential fashion were cited as major strengths of the course. Juxtaposition of basic science and clinical material and utility in reviewing for the United States Medical Licensing Examination were also cited as strengths. The diversity of the basic science material involved in completing the cases drew overwhelming enthusiasm from students and facilitators alike. In conclusion, the course successfully employs computer and information science technology, which will be of increasing importance to future physicians. The course also serves as an effective bridge to the clinical years of medical school and as a study adjunct for the USMLE.

The authors describe the advantages and disadvantages of central governance of the undergraduate medical curriculum as contrasted with traditional departmental approaches, based upon their school's experience with a new centrally governed curriculum during the preceding four years. Central governance has more advantages, but also more costs, compared with traditional departmental approaches. Central governance does what it was intended to do: it provides rational and integrative mechanisms for ensuring a broad general education in medicine focusing on the doctor-patient relationship. It also provides an effective mechanism for dealing with "turf" and time issues in the curriculum while allowing for and encouraging changes and providing mechanisms for evaluating those changes. However, as the allocation of resources and rewards remains more departmentally than centrally based, a major challenge of central governance has been to help faculty resolve a "conflict of loyalty" (the sense of serving two masters) between school and department, particularly in the evaluation and reward of teaching. On balance, central governance provides a powerful means of introducing broad-based reforms into all elements of the undergraduate medical curriculum, but it requires ongoing collaboration with faculty and chairs to assist them in negotiating competing pressures and priorities as they strive to become excellent teachers.

Removal of the Fc region of human IgA m components by treatment with IgA-specific protease from Neisseria gonorrhoeae reduces the neutrophil chemotactic inhibitory activity associated with IgA M components. This observation, along with the failure of an IgA halfmer paraprotein to inhibit neutrophil chemotaxis, emphasizes the importance of the IgA Fc region in the inhibition of neutrophil chemotaxis by IgA M components.

A case of multiple myeloma with no monoclonal protein synthesis is reported. The patient had hypogammaglobulinemia, bone marrow invasion, osteolytic lesions, and plasma cell tumors. The absence of protein synthesis has been demonstrated in bone marrow culture with tritiated leucine. No evidence of immunoglobulin production was found. Bone marrow or plasma cell tumor biopsy may be the only method of diagnosis in such cases.

An unusual human cryoglobulin complex was characterized as a two-component system containing monoclonal immunoglobulin G (IgG) and serum albumin in a 1:2 mole ratio. This complex appeared to be an antibody-antigen complex, since the mole ratio was appropriate and the isolated Fab of the IgG associated with the albumin. The cryoglobulin apparently arose as a result of specific association and/or aggregation of the IgG albumin adduct, since the cryoglobulin complex formed a crystalline precipitate. The IgG and albumin were separated and characterized with respect to immunological cross-reactivities, sedimentation velocities, isoelectric properties, and amino acid composition. The extent of precipitation of the cryoglobulin complex was maximal at pH 7.8, was decreased by added ions including citrate, ethylenediaminetetraacetic acid, NaCl, and CaCl2, and was decreased by increasing temperature. Both the nature of the cold-precipitable complex and the solubility properties differed from those described for other cryoglobulins.

beta 2-Microglobulin is a low molecular weight protein with sequence homology to immunoglobulins. As a portion of the HLA complex this protein is an important cell-surface structure. Under normal conditions beta 2-microglobulin is synthesized and shed by many cells, particularly lymphocytes, and is detectable in the circulation of normal individuals. Because of its small size it is normally filtered readily at the glomerulus and is catabolized by proximal tubular cells of the kidney. Impaired renal function and hyperproduction of beta 2-microglobulin are both associated with increased serum levels. A function for beta 2-microglobulin as a modulator of lymphocyte surface and as a potential regulator of the immune system is proposed.

Receptors for the Fc portion of immunoglobin on human peripheral blood cells were enumerated by rosette formation with ox erythrocytes sensitized with rabbit IgG, IgA, and IgM. A large percentage of purified polymorphonuclear leukocytes and monocytes were found to express receptors for IgA. These receptors were also found to exist on a significantly greater percentage of lymphocytes than was previously observed. The receptors for IgA were specific, as verified by blocking studies using purified human immunogloblins. In addition, some polymorphonuclear leukocytes and monocytes were observed concomitantly to posses independent receptors for both IgG and IgA. These studies may indicate that IgA can cooperate with monocytes or polymorphonuclear leukocytes through receptors for IgA on these cells and perhaps mediate immune defense on mucosal surfaces. Initial studies on antibody-dependent cellular cytotoxicity suggested that IgA alone is ineffectual in supporting cytolysis by nonactivated human peripheral blood cells.

We have analysed and compared the fine specificity and behavior in various immunoassays of 10 mouse monoclonal antibodies, from three independent laboratories, directed against IgA1, IgA2 or non-IgA2m(2). The following observations were made. (1) Although all of the monoclonal antibodies were specific for a particular IgA subclass or isoallotype in a radioimmunoassay, three of them were not specific when tested in indirect immunofluorescence on plasma cells derived from pokeweed-activated peripheral blood lymphocytes. In this highly sensitive system, contrary to direct immunofluorescence previously performed using formalin-fixed lymphoid tissue, the anti-IgA1 69.114 reacted with some of the IgA2 plasma cells, the anti-IgA2 DLDB7 reacted with some of the IgA1 plasma cells and the anti-IgA2 16.512 dimly reacted with all IgM plasma cells. (2) Among the eight anti-IgA subclass antibodies, seven were directed against the CH2 domain of IgA whereas the anti-IgA1 1-155-1 recognised an epitope destroyed by Streptococcus sanguis IgA1 protease and localised in the hinge region of IgA1. The two anti-isoallotype antibodies were directed against epitope(s) probably localised in the 65 C-terminal amino acid residues of the alpha-CH3 domain. All of the 10 antibodies were able to react with endogeneously produced surface IgA on B-cells. (3) Using monoclonal anti-IgA subclass antibodies in radioimmunoassay may be hazardous in the absence of knowledge of their affinity constants and of careful control experiments: some of the antibodies were not sensitive in radioimmunoassays designed to measure the serum titer of specific IgA1 and IgA2 antibodies. Moreover, major differences were observed between the different monoclonal reagents with respect to the influence of the size of IgA on a solid-phase sandwich radioimmunoassay. While three of the anti-IgA1 underestimated dimeric IgA relative to monomeric IgA, the fourth anti-IgA1 and all the anti-IgA2 overestimated dimeric IgA relative to monomeric IgA, by a factor sometimes close to 7.

The bone marrow plasma cells of 52 patients with various kinds of monoclonal gammopathies were studied by electron microscopy, and compared to the bone marrow plasma cells of 22 patients with reactive plasmacytosis. Virtually every marrow from patients with myeloma and macroglobulinemia contained plasma cells with disparity between the nuclear maturation and cytoplasmic differentiation. This asynchronous development was not present in plasma cells of reactive marrows nor in plasma cells from patients with megaloblastic anemias. The degree of asynchrony observed in myeloma and macroglobulinemia was proportional to the extent of disease as judged by clinical criteria. For the most part plasma cells of patients with non-myelomatous monoclonal gammopathy failed to exhibit significant asynchrony. These observations are consistent with the view that multiple myeloma is a neoplastic disorder with a definably malignant-appearing cellular proliferation.

Two patients had a previously unrecognized form of crystallocryoglobulinemia. Their clinical presentations were similar, consisting of necrotizing vasculitis and purpura involving the legs. Analysis of each cryoglobulin complex showed that two components, albumin and a monoclonal IgG-lambda, were present, and both components were needed in a fixed ratio for precipitation. In addition, cryoprecipitation occurred in serum, but not plasma, due to citrate inhibition of complex formation. Our findings suggest that the monoclonal IgGs have the properties of antibodies directed specifically against a calcium-dependent antigenic site on human albumin, and that the resultant IgG-lambda-albumin immune complexes crystallized in the cold.

A patient with plasma cell leukemia and myelofibrosis excreted free immunoglobulin light chains and an abnormal monoclonal immunoglobulin (Ig) A in her urine. The IgA that was present in serum and urine had a sedimentation coefficient of 4.0 S. The molecule was comprised of both heavy and light chains but was antigenically deficient compared to normal IgA. As excreted in the urine, the protein appeared to be a half-molecule of IgA, with a partial deletion in the heavy chain, probably involving part or all of the C-terminal domain.

Fluorescent antibody to antigenically distinct portions of 7S gammaglobulin was used to study the occurrence of H-chains and L-chains of types I and II within single cells. Individual lymphoid cells contained both H-and L-chains, but individual cells did not contain both antigenic types of L-chains.

Two antigenic types of naturally occurring proteins related to the papain produced F(c) fragment of gammaG-globulin have been studied. Most normal and myeloma gammaG-globulins are related to one or the other of these proteins, based on antigenic and structural characteristics of their heavy chain. Molecules bearing the determinant "Cr" are approximately 10 times as abundant as those bearing the determinant termed "Zu" in pools of normal gammaG-globulin and among a large group of gammaG-myeloma globulins. Both populations have properties of typical gammaG-globulin antibodies. Splenic cells, stained for these two populations with specific fluorescent antibody preparations, are found to contain one or the other of the two populations of gammaG-globulin, but not both. Approximately 10 times as many cells contain the Cr determinant as contain the Zu determinant.

Two populations of immunologically distinguishable 7S gamma globulins in normal human serum and two corresponding antigenic types of myeloma 7S gamma globulins have been detected with rabbit antiserums to proteins associated with pathological conditions, the differences being related to the H-chains of 7S gamma globulin. No relationship exists with type I and type II antigenic classification, determined by L-chains. Human serums with various hereditary gamma globulin (Gm) specificities contain both types of 7S gamma globulin.