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We report a patient with non-Hodgkin's lymphoma of small lymphocytic type with IgM-kappa monoclonal gammopathy who developed extranodal involvement with orbital and nasal manifestations, followed by generalized subcutaneous nodules. Immunological study disclosed that the peripheral blood and the subcutaneous nodule were both involved in a common monoclonal proliferation of B cells at various stages of differentiation, including secretory cells which accounted for the serum paraprotein. The secretory capacity was far greater in the peripheral blood than in the subcutaneous tissue. These clinical and immunological manifestations might reflect the physiological behaviour of a particular B cell subset which shows a preference for mucocutaneous sites to secrete IgM in the peripheral blood.

40 patients with idiopathic thrombocytopenic purpura (ITP) were studied for T-cell abnormalities using a panel of monoclonal antibodies (Mc Abs). These patients showed a tendency to have a decreased OKT4+: OKT8+ ratio compared with normal subjects and a significant increase was observed in OKT10-positive cells in ITP patients. Further analyses were made utilizing McAbs of different subclasses in combination (BMA040 mouse IgG1 McAb, helper/inducer T and BMA081 mouse IgG2 McAb, suppressor/cytotoxic T). An increased proportion of cells reactive with both BMA040 and BMA081 McAbs (double-labelled cells) was demonstrated in patients with ITP compared with the normal controls. Furthermore, there was an inverse correlation between the proportion of “double-labelled cells” and the platelet counts. These data suggest that abnormalities of the T-cell subsets in the peripheral blood may play an important role in the pathogenesis of ITP.

A 48-year-old woman was hospitalized because of severe thrombocytopenia, leg edema, and fever. Intravenous immunoglobulin therapy was administered, but no efficacy was obtained. Her bone marrow was dry-tap, and fibrosis was found in the biopsy specimens. A positron emission tomographic study showed FDG-avid lymphadenopathy and hepatomegaly. Biopsy specimens of axillary lymph nodes showed Castleman's disease-like findings. Since she then developed severe proteinuria and massive pleural effusion, steroid therapy was started, providing temporary relief of symptoms other than the thrombocytopenia. However, rapid worsening of her general condition prompted us to attempt rituximab as salvage therapy. The pleural effusion, edema, and proteinuria disappeared soon after starting rituximab administration. Platelet counts also normalized and fibrosis of the bone marrow showed amelioration. Recently, a variant of multicentric Castleman's disease, termed the TAFRO syndrome, has been proposed, and our patient's features fit the diagnosis of this syndrome. Rituximab might be considered as a therapeutic option in such cases.

We report a 39-year-old man with intravascular large B-cell lymphoma (IVLBCL) who had been treated as a case with pulmonary arterial hypertension (PAH) for one year. After he became worse, diffuse pulmonary (18)F-fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) suggested the existence of IVLBCL in the lung showing normal CT images. The diagnosis was confirmed with random transbronchial lung biopsy, and he was then successfully treated. Since IVLBCL presenting PAH has been rare and is difficult to diagnose, early application of FDG-PET may provide early recognition of the disorder, leading to a better outcome.

To clarify the components of cellular immunity responsible for defense against the clonal development of myeloma cells, we tested the capacity of human peripheral blood lymphocytes (PBLs) to inhibit the growth of 3 human myeloma cell lines (RPMI 8226, OPM-1, and OPM-2). RPMI 8226 was found to be sensitive to PBLs, showing almost complete growth arrest when cultured with PBLs for 72 h. Inhibition of the growth of RPMI 8226 cells required direct cell-to-cell contact but not presensitization of the PBLs to the target cells, and did not depend on the generation of soluble factors. CD3+, CD4-, CD8- and CD16- cells were found to be the major subset contributing to inhibition of the growth of RPMI 8226 cells, and this growth inhibition was cytostatic rather than cytotoxic. These characteristics distinguished it from growth inhibition mediated by the natural killer system. Impaired PBL-mediated growth inhibition of RPMI 8226 cells was found in patients with various hematologic diseases, including myeloma. It therefore appears that the CD3+, CD4-, CD8- and CD16- cell subset might be involved in tumor immunity in myeloma.

Six cases of monocytoid B-cell lymphoma (MBCL) developing in extranodal sites (thyroid, three; stomach, two; rectum, one) are described. Patients were all women aged 46 to 65 years (median, 53 years). Three patients with thyroid lymphoma presented with an increasing goiter, two with positive serum antithyroid antibodies, and one patient had chronic lymphocytic thyroiditis (CLTH). The histologic type of surgically resected specimens was a diffuse proliferation of atypical lymphoid cells with monocytoid appearance, i.e., abundant pale cytoplasm with distinct cell border and small reniform nucleus. These cells were CD20+, 22+, 24-, 9- showing their B-cell origin. The monoclonal nature of the proliferating cells was confirmed by restricted expression of immunoglobulin (Ig) light chain and/or gene rearrangement study in three cases. Two cases of thyroid lymphoma in which the monoclonality could not be confirmed had histologic appearances characteristic of malignant lymphoma. All three patients with gastric or rectal lymphoma had reactive lymphoid hyperplasia (RLH) near the tumors. These findings showed presence of MBCL in the extranodal sites with invariable coexistence with lymphoid follicles formed by CLTH in thyroid or RLH in stomach and rectum.

A 48-year old man was admitted with idiopathic fever, and subsequently diagnosed as having hemophagocytic lymphohistiocytosis (HLH). Though an extensive series of laboratory examinations failed to demonstrate an apparent etiology, empirical use of steroids achieved remission. About two years later, the patient developed Pneumocystis Jiroveci pneumonia and was diagnosed as HIV-positive. Based on this case, HIV-screening tests would be performed whenever we encounter HLH in Japan, where the number of HIV-positive patients is increasing.

Summary A study was made of 29 patients with monoclonal gammopathies to detect aberrations in immunoglobulin (Ig) light chain isotype expression in lymphocytes at various levels of B-cell differentiation, namely, circulating surface Ig positive (SIg +) cells, Ig-secreting cells (plaque forming cells, PFC) and mitogen-induced PFC. By using kappa-lambda analysis, two major phenotypes of aberrant Ig light chain isotype expression were found in circulating B cells at these three levels of differentiation: an absolute increase in B cells bearing the same Ig light chain isotype as that of monoclonal protein (clonal B-cell excess), and a relative decrease in those B cells (isotypic discordance). Isotypic discordance (ID) was found to be essentially negative in patients with monoclonal gammopathy of undetermined significance (MGUS) provided that they were in a stable condition. In myeloma patients, ID was found only in stage I, except for a remission case of stage III (4/7 in stage I, 0/8 in stage II, and 1/6 in stage III). ID was not restricted to a circulating SIg+ cell level but was also demonstrable at a spontaneous or pokeweed mitogen-induced PFC level. However, ID was negative at a PFC level induced by Staphylococcus aureus Cowan I. Clonal B-cell excess (CE) was frequently found in patients with active myeloma but not in stable patients (0/8 in MGUS, 1/7 in stage I, 8/8 in stage II, and 4/6 in stage III). CE was positive not only at a circulating SIg+ cell level but also at a circulating PFC level. Furthermore, patients with CE at a PFC level were found to have a higher proliferating capacity, defined as a percentage labelling index of marrow myeloma cells, than those without CE at a PFC level (P

Functional and structural characteristics of interleukin 2 (IL-2) receptors on B-cell chronic lymphocytic leukemia (B-CLL) cells were analyzed by a proliferation assay, IL-2 binding assay and cross-linking study. In the 3H-thymidine incorporation assay, purified B-CLL cells from four out of sixteen cases, in which the percentage of Tac antigen (Tac Ag) positive cells in peripheral blood lymphocytes ranged from 0 to 48.8%, responded to IL-2 (100 U/ml) after both 3- and 6-day incubation. No relationship was found between the responsiveness to IL-2 and the percentage of Tac Ag positive cells. In the radiolabeled IL-2 binding assay, however, B-CLL cells from all seven cases examined, including three cases with mitogenic response to IL-2 and four cases without mitogenic response, were shown to have both high- and low-affinity receptors. The number of high- and low-affinity receptors per cell ranged from 29-186 and from 420 to 1,800, respectively. Furthermore, with the affinity cross-linking method p55 (Tac Ag) and p70/75 were found even in cases without mitogenic response in their B-CLL cells. In conclusion, the B-CLL cells so far examined possessed high-affinity IL-2 receptors consisting of p55 and p70/75; nevertheless, this was not sufficient to respond to the mitogenic signal of IL-2.

Thromboembolism has been shown to play a role in the pathogenesis of inflammatory bowel disease (IBD). A possibility exists that lipoprotein (a) [Lp(a)], a newly-discovered prothrombotic factor, also participates in the development of at least some cases of IBD. Marked elevation of serum Lp(a) levels was observed in a young patient with ulcerative colitis. A biopsy specimen of the rectal mucosa showed findings compatible with ulcerative colitis, as well as small vessel thrombus occurring within the muscularis mucosa in the rectum. Serum Lp(a) levels were markedly elevated on admission (71 mg/dl), with a gradual decrease to 46 mg/dl on discharge. Moreover, serum Lp(a) levels decreased in parallel with clinical improvement. In the quiescent clinical stage, no small vessel thrombus was observed in the mucosa on follow-up colonoscopy. The association between IBD and hyper-Lp(a)-emia would be presumable but it has been, to our knowledge, previously unreported. The case reported here would be the first young patient, suggesting the presence of hyper-Lp(a)-emia and small vessel thrombus formation occurring in association with the development of ulcerative colitis.

VLA-5 recognizes the GRGDSP sequence of fibronectin (FN) in the extracellular matrix (ECM). We examined the role of beta1 integrin in the spreading of the human plasma cell line, FR4ds, induced by FN and laminin (LN). We first examined the role of VLA-5 in the spreading induced by FN. Anti-alpha4 antibody induced 46.4% inhibition, whereas anti-alpha5 had no effect. A combination of anti-alpha4 and anti-alpha5 enhanced the inhibition of spreading significantly. Complementary inhibition was also demonstrated using the GRGDSP peptide plus anti-alpha4 and the GRGDNP peptide of LN plus anti-alpha4. The results suggested that VLA-5 is a regulator of VLA-4 and that it is involved in the recognition of GRGDNP. We then examined the role of VLA-5 in the spreading induced by LN. Anti-alpha6 induced 53.1% inhibition. Anti-alpha5 alone had no effect. A combination of alpha5 and anti-alpha6, however, significantly enhanced the inhibition of spreading. The combination of GRGDSP plus anti-alpha6 and GRGDNP plus anti-alpha6 resulted in complete inhibition. These results suggested that VLA-5 participates in the recognition of LN cooperatively with VLA-6 and that VLA-5 is a common regulator of VLA-4 and the LN receptor, VLA-6.

Autologous mixed lymphocyte reaction (AMLR)-induced suppressor function was studied in 12 patients with chronic idiopathic thrombocytopenic purpura (ITP). The function was found to be significantly impaired (20 +/- 55%; p less than 0.005) compared with normal subjects (69 +/- 25%). AMLRs in these patients were significantly decreased (p less than 0.05) compared with normal subjects. There was no significant correlation between AMLR-induced suppressor function and platelet counts. Nine patients were studied for AMLR-induced suppressor function before and after splenectomy. The platelet counts increased significantly as a result of splenectomy, but the AMLR-induced suppressor function showed no significant improvement. The results of this study suggest that suppressor dysfunction in ITP may be an immunologic defect irrespective of disease activity. We consider that this abnormality may reflect in vivo failure of the immunoregulatory (feedback) mechanism in ITP.

The local immunologic phenomena in the thyroid gland of 16 patients with chronic lymphocytic thyroiditis (CLTH) were investigated; 5 of these cases were associated with thyroid non-Hodgkin's lymphomas (NHL). All patients were admitted because of struma, growing slowly in patients with CLTH alone and rapidly in those with associated thyroid NHL. CLTH was confirmed by histologic findings, including the presence of lymphoid follicles or thyroid autoantibodies in the serum in all 16 patients. Immunologic study revealed that all thyroid NHL were of the B cell type. Surface maker study of suspended cells showed that the percentages of E-rosette-forming cells in patient with CLTH and thyroid NHL (38.0 +/- 10.0%) and in patients with CLTH alone (45.0 +/- 11.9%) were between those of B cell NHL of lymph node and B cell hyperplasia reported by others. Immunohistochemical studies confirmed the reactive nature of lymphoid follicles. Subset distribution of T and B lymphocytes in patients with CLTH and thyroid NHL markedly contrasted with that in patients with CLTH alone: an increased ration of CD8+ cells (suppressor/cytotoxic cell) to CD4+ cells (helper/inducer cell). There was a marked increase in the number of immunosuppressive acidic-protein(IAP)-containing macrophages in the thyroid lesion and serum IAP level in patients with thyroid NHL. These findings provide evidence of a difference in the local immunologic conditions in CLTH alone compared to CLTH complicated by thyroid NHL.

A new B-cell line (ONHL-I) was established from non-Hodgkin's lymphoma. ONHL-I was free from Epstein-Barr virus nuclear antigen and expressed CD20, CD24, and slg (μ, δ, γ and κ), thus being equivalent to the mature B-cell stage. Chromosome analysis revealed a markedly abnormal pattern including 14q+ and 6q- In accordance with the positive expression of surface K light chains, one of the K genes was found to be rearranged. However, rearrangement of the A locus was also detected, contrary to the supposed hierarchy for the rearrangement of the light-chain genes. The cell line showed rearrangement of the bcl-2 gene. Further, the rearranged fragments of the JH, CA, and bci-2 genes were of the same size in the EcoRI and HindIII digests on the same filter. This may suggest that the bcl-2 gene is juxtaposed with the JH and CA locus. The proliferation of ONHL-I was inhibited by adding Staphylococcus aureus Cowan I or 12-O-tetradecanoyl-phorbol-13-acetate. During this growth inhibition, the expression of c-myc decreased, while that of bcl-2 mRNA remained steady. This result suggests that not the bcl-2 gene but other oncogenes, such as c-myc, play a key role in the proliferation of ONHL-I. This agrees with the hypothesis that the bcl-2 gene is not concerned with aggressive proliferation but with cell survival. This new cell line will therefore be of value in studying the differentiation and tumorigenesis of B cells.

Twenty-seven patients with stages I or II thyroid lymphomas were investigated immunologically. Approximately 60% of these patients had a goiter for longer than 1 year. Both the tests for serum antithyroid antibodies and histologic findings of the resected specimens showed that chronic lymphocytic (autoimmune) thyroiditis was usually present. The tumors were classified histologically as seven cases of follicular lymphomas and 20 cases of diffuse lymphomas. Immunocytologic study on suspended cells and immunohistologic study on frozen tissue sections showed that neoplastic cells in 22 of 27 cases expressed restricted immunoglobulin light chains. In remaining five cases, the neoplastic cells reacted with B-1, Leu-10, and/or Leu-14. These results indicate that thyroid lymphomas are exclusively B-cell-derived tumors.

Neoplastic cells of 18 patients with multiple myeloma were studied using a panel of 6 monoclonal antibodies to B cells and monospecific antisera against the light chain types of immunoglobulin. OKT10 bound to the myeloma cells of all the patients, although only a small percentage of the cells reacted in 3 instances. Monoclonal sIg was present in 5 patients. HLA-DR antigen detected with OKIa-1 was found in 5 patients. B1 bound to a small percentage of the myeloma cells only in 2 patients who had received treatment. The B1+ cells were always sIg+. In 3 patients, BA-2 reacted with the myeloma cells. BA-1 and BA-3 invariably did not react with the cells. Myeloma cells with B cell markers were found more frequently in treated patients than in untreated patients. The RPMI8226 line was also studied and found to react with OKT10 and BA-2. The results of this study show the presence of phenotypic variety in myeloma cells.

A case of chronic leukemia is reported. Malignant cells had the morphology of lymphocytes and an affinity for skin. Cytochemically, they were peroxidase negative, and NaF-resistant alpha-naphthyl esterase positive. The peripheral mononuclear cells formed E-rosettes and reacted with Leu 1 and OKM1. They were unreactive with OKT3, OKT4, OKT6, OKT8, and OKIa1. The cells did not possess surface IG, C3b receptors, or IgG Fc receptors (EAIgG). They responded weakly to phytohemagglutinin, and did not respond to concanavalin A. The cells did not adhere to Petri dishes or phagocytose latex beads. It is concluded that it was a case of OKT3-, OKM1+, EAIgG- T-cell chronic lymphocytic leukemia. This suggests that OKT3 does not recognize all peripheral T-cells, and that OKM1 is not specific for the monocyte-myeloid lineage. These cells may be useful in the characterization of E+, OKM1+ subset of peripheral mononuclear cells.

Tubuloreticular inclusions (TRI) and paired cisternae (PC) were induced in lymphocytes of normal individuals after incubation with Staphylococcus aureus Cowan 1. TRI were initially detected in lymphoid cells on day 2 (48-h culture). The frequency of TRI-positive cell sections on day 5 increased about twofold over those on days 2-4. On day 7, TRI were predominantly seen in lymphoplasmacytoid cells or plasmacytoid cells, with an incidence of up to 18% of sections. The regions in these cells were most extensive and anastomosed with the cisternae of adjacent well-developed rough endoplasmic reticulum (RER). TRI formation appears not to be essential for mitogen-induced B-cell differentiation to plasmacytoid cells, because pokeweed mitogen (PWM) failed to induce TRI. The diverse expressions of TRI induction between these two mitogens may be due to a difference in B-cell activation mechanisms. Paired cisternae were observed in a great majority of mitotic cells at various stages. These were encountered most frequently on day 4. PC were also seen in the PWM-stimulated culture. Our observations suggest that PC formation may be related to new formation of RER as well as to reconstruction of the nuclear envelope.

Tubuloreticular inclusions (TRI) were induced in normal blood lymphocytes after incubation with Staphylococcus aureus Cowan 1 (STA), but they were not induced by pokeweed mitogen (PWM), as we reported previously. TRI were also induced in Raji cells when grown in the medium of STA culture. Alpha-interferon (alpha IFN) was detected only in the medium of STA culture and not in PWM culture. The cells of PWM cultures formed TRI when exposed to various concentrations of human leukocyte alpha IFN. The incidences of TRI-positive cells in the presence of 50-500 IU/ml of alpha IFN were 3-5% on day 2 and increased to 10% on day 7. On days 5-7 of the PWM cultures, plasmacytoid cells containing TRI were seen not infrequently. In the presence of a high concentration of alpha IFN (10,000 IU/ml), which was sufficient to inhibit cell growth and differentiation, the growth of the TRI region was not altered and the incidence of TRI-positive cells was 9% on day 2 and increased to 15% on day 7. Our observations suggest that the TRI formation in STA culture is attributable to the alpha IFN produced endogenously by STA-stimulated cells and that some relationship might exist between the incidences of TRI-positive cells in these mitogen-stimulated cultures and the biologic functions of IFN.

Monoclonal gammopathy (IgG, lambda) in a 37-year-old man with Hashimoto's thyroiditis, was markedly decreased after thyroidectomy. Histological examination of the thyroid showed large lymphoid follicles surrounded by a massive proliferation of plasma cells. Immunological studies revealed that interfollicular plasma cells stained monotypically for lambda chain, findings in keeping with a diagnosis of plasmacytoma of the thyroid. In addition, there was kappa monotypic staining of the lymphoid follicles and absence of tangible body macrophages, indicating the presence of a follicular lymphoma derived from a separate cell line from the plasmacytoma.

Four cases of thyroid lymphomas are presented showing curious histologic difficult to distinguish from severe lymphocytic thyroiditis by routine histologic study alone. The age of the patients ranged from 39 to 63 years. Three female patients suffered from autoimmune (lymphocytic) thyroiditis for 2 to 20 years until the present illness. A male patient had no history of thyroiditis. Rapid growth of struma in these patients suggested an evolution of malignant lymphomas. Histologic study results showed that small atypical lymphoid cells with slightly irregular and indented nuclear contour surrounded randomly distributed secondary follicles as a wide mantle. Immunohistologic staining showed that these atypical small lymphoid cells expressed surface properties intermediate between mantle-zone lymphocytes and germinal center cells with a restricted expression of kappa chain in three cases. Stages of tumors were stage I in three cases and stage II in one case. The findings demonstrated were intermediate lymphocytic lymphomas of the thyroid.

A case of plasma cell leukaemia of non-producer type is described. The patient presented with typical clinical features of plasma cell myeloma, including multiple osteolytic lesions, hypercalcaemia, renal failure and reduced polyclonal immunoglobulins, except that M-component was not detected in either the serum or urine. Morphological examinations showed a plasmacytoid appearance of the neoplastic cells, while immunological studies failed to detect cytoplasmic immunoglobulin or secretory capacity. The surface phenotype of CD38+, PCA-1+, DR-, CD20-, CD24-, CD9-, CD10- and surface immunoglobulin- was compatible with mature plasma cells. Chromosomal analysis showed the 14q+ marker due to translocation (6;14) and deletion of the short arm of chromosome 1. Analysis of immunoglobulin genes revealed the presence of heavy chain gene rearrangement, but the light chain genes, both kappa and lambda, remained in germline configuration. Such defective immunoglobulin gene rearrangement may be responsible for the failure of immunoglobulin biosynthesis and secretion by the neoplastic plasma cells. Furthermore, it is suggested that the morphological and phenotypic development of B cells may not necessarily depend on immunoglobulin light chain gene rearrangement, and that the oncogenic event in myeloma may occur at an earlier stage of B cell differentiation.

A case of "nonsecretory" myeloma is described. The patient had typical osteolytic lesions and marked infiltration of myeloma cells in the bone marrow, and plasma cell leukemia. A good partial remission was obtained with Melphalan, but the patient relapsed and died one year later. Immunofluorescent and immunoelectroscopic studies on the myeloma cells demonstrated the presence of cytoplasmic gamma-and kappa-chains at the initial stage and of only kappa-chains at a relapse. The electron microscopic method for polysome analysis indicated that both L-and H-chains were synthesized on membrane-bound polysomes initially, but the ability to produce H-chain was missing at the relapse.

Aspergillus vegetative endocarditis developing in a patient with acute lymphocytic leukemia during the phase of hematological remission has led to a fatal outcome, complicated with severe hemolytic anemia with red cell fragmentation. Systemic aspergillosis may involve heart valves with underlying disorders, but seldom affects intact valves even in severely compromised hosts. Among such rare cases so far reported, only 2 cases have been documented in acute leukemia, despite a huge prevalence of pulmonary and systemic aspergillosis in hematological malignancies. Our present case is essentially the same as in the preceding two cases in that endocarditis occurred during the hematological remission. These clinical, observations may suggest that every leukemic patient suffering from aspergillosis is susceptible to the valvular complication after, rather than during, the period of severe myelosuppression, because platelets play an important role in the formation of thrombotic lesions.

A successful embolization for life-threatening uterine hemorrhage is described in a patient with acute promyelocytic leukemia and disseminated intravascular coagulation. On admission the patient was in the 6th week of gestation with incomplete abortion and uterine hemorrhage. In addition to combination chemotherapy and anticoagulant therapy, dilatation and curettage were also performed. After the operation the uterine hemorrhage was progressively increased in amount and was not responsive to usual measures. Embolization of bilateral uterine arteries using Gelfoam was performed with a dramatic improvement of the hemorrhage.

Summary Human myeloma cells are malignant counterparts of plasma cells which represent the most differentiated B cells. Myeloma cells are, however, heterogeneous in their surface antigen expression (Katagiri et al, 1984, 1985), which may reflect that normal plasma cells have a spectrum of differentiation. To test this hypothesis, immunoglobulinsecreting cells (ISC) of non-neoplastic nature were studied with regard to their surface antigen expression by using a combination of reverse haemolytic plaque assay and complement-dependent cytolysis. Non-neoplastic ISC were found to have a broad spectrum of differentiation stages from the immature type of CD20+, HLA-DR+, CD38+ in the peripheral blood to the mature type of CD20–, HLA-DR–, CD38+ in the bone marrow. In patients with polyclonal B cell activation (PBA), ISC showed a more immature antigen expression in comparison with ISC in normal controls or patients without PBA. The surface antigen development of ISC was clearly demonstrated throughout the stages in the analysis of mitogen-induced ISC in vitro. No significant difference in the surface phenotype of ISC was found among heavy chain classes. Thus, non-neoplastic ISC show a spectrum of differentiation similar to that of myeloma cells, depending on the site where ISC are located, and on the degree of PBA in vivo.

Two distinct cell lines (OPM-1 and OPM-2) were established from the peripheral blood of a 56-year-old female myeloma patient at the stage of terminal leukemic evolution associated with loss of cytoplasmic immunoglobulin heavy chain (G lambda----lambda). The lines grew in suspension with a doubling time of 36-42 hr and 30-36 hr, respectively. EBNA was absent from both lines. The lines synthesized cytoplasmic lambda-chain, but had no detectable surface immunoglobulins. Fc receptors and complement receptors could not be detected in either line. The lines had very complex chromosomal abnormalities, but the patterns of chromosomes differed greatly between the two lines. The two lines, together with the RPMI 8226 line established by Matsuoka et al. (1967), were analyzed for phenotypic expression as defined by a panel of monoclonal antibodies to B cells (B1, BA-1, BA-2, BA-3, OKIa-1 and OKT10/BMA0100). Neither OPM-1 nor OPM-2 reacted with any of the antibodies tested except OKT10. OPM-1 cells reacted weakly (less than 30%) with OKT10/BMA0100, while OPM-2 cells showed a fluctuating reactivity, ranging from 40 to 80%, with OKT10/BMA0100. In contrast, RPMI 8226 reacted strongly with OKT10 and BA-2. These results demonstrate the presence of phenotypic heterogeneity in all 3 myeloma cell lines, suggesting that the lines might represent different stages of terminal B-cell development.

Distribution of membrane-bound Gc protein (mGc) in normal lymphocyte subpopulations and leukemic lymphocytes was studied using a rabbit antiserum specific to Gc protein. Forty to fifty percent of the normal peripheral blood mononuclear cells were stained with anti-Gc antiserum by membrane immunofluorescence, and almost all of the B cells (B1+) and NK cells (Leu 11+) were mGc-positive. Only a few resting T cells (T3+) reacted with anti-Gc, but mGc appeared in a significant number of the T cells after activation by PHA. The distribution of mGc on leukemic lymphocytes of various types nearly corresponded to that in normal lymphocyte subpopulations.

A case of malignant lymphoma with a helper activity of neoplastic cells is reported. On admission, a significant number of plasma cells of polyclonal nature were seen in the peripheral blood, and polyclonal hypergammaglobulinemia was seen. The biopsied lymph node showed poorly differentiated lymphocytic lymphoma with marked proliferation of plasma cells. At the terminal stage, the patient became leukemic in contrast with the disappearance of plasma cells from the peripheral blood. Although the leukemic cells failed to form sheep erythrocyte rosettes, they were considered to be of T-cell origin morphologically. Cytochemically, they had a "dot"-like pattern of alpha-naphthyl acetate esterase and acid phosphatase activity. Ultrastructurally, they had highly convoluted nuclei, and cytoplasmic clustered dense bodies. They showed marked helper activity on pokeweed mitogen-induced B-cell differentiation in vitro. This case may provide a novel view concerning the cause of hypergammaglobulinemia induced by lymphoproliferative disorders.

This report describes studies of a man suspected of having primary cortisol resistance. This conclusion is based on his high plasma cortisol levels and high 24-h urinary 17-hydroxycorticosteroid and cortisol excretion, plus the fact that he had no manifestations of Cushing's syndrome. Among family members tested, his mother also had hypercortisolemia. Both mother and son had high levels of unbound plasma cortisol, but their plasma ACTH concentrations were within the normal range. Both were partially resistant to dexamethasone adrenal suppression, and both had mild hypertension without hypokalemia. To study this apparent end-organ resistance to cortisol, we examined the glucocorticoid receptors in peripheral mononuclear cells. Using whole cell assays, glucocorticoid receptors in both patients were found to have reduced total binding capacity. We conclude that these two patients, members of the same family, have primary cortisol resistance accompanied by a reduced number of glucocorticoid receptors.