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Biomedical subjects

W C Chan

Publications and source records attributed to W C Chan.

At least 163 records · Page 9Linked to original sources

Malignant lymphoma of the skin in children.

The clinical and histopathologic findings in eight cases of malignant lymphoma of the skin in children are presented. All patients had skin lesions as a primary manifestation of the disorder. Three patients had simultaneous regional lymph node involvement documented by the findings of subsequent biopsies. The majority (five patients) had solitary nodules involving the skin of the head and neck region. Three of the skin biopsy specimens were classified as lymphoblastic lymphoma, two large cell lymphoma, two mixed small and large cell lymphoma, and one small cleaved cell lymphoma. Disseminated disease subsequently developed in four patients in an interval that ranged from 4 to 30 months after diagnosis. The follow-up period ranged from 8 to 56 months, and median survival was 56 months. A literature review of 33 previously reported patients and our eight patients indicate that: skin of the head and the neck region is the most common site of involvement (56%); the majority of lymphomas are diffuse (93%); lymphoblastic lymphoma is the predominant type (53%), with a high proportion showing a non-T-cell phenotype; Burkitt's lymphoma and Hodgkin's disease of the skin are extremely rare; and most patients presented in an early clinical stage (Stage IE 56%, Stage IIE 21%), and prolonged disease-free survival was seen mostly in Stage I patients. The cumulative probability of survival for Stage I patients at 24 months was 0.71; while for Stages II to IV patients combined, it was 0.33 at 26 months.

Adolescent↗

The p75 peptide is the receptor for interleukin 2 expressed on large granular lymphocytes and is responsible for the interleukin 2 activation of these cells.

There are at least two interleukin 2 (IL-2) binding peptides: one is the Mr 55,000 peptide (p55) reactive with the anti-Tac monoclonal antibody, and the other is a Mr 75,000 non-Tac IL-2 binding peptide (p75). Independently existing Tac or p75 peptides represent low-affinity IL-2 receptors, whereas high-affinity IL-2 receptors are expressed when both peptides are present and associated in a receptor complex. It has long been known that normal large granular lymphocytes (LGL) or leukemic cells from the patients with abnormal expansions of LGL can be activated by IL-2 not only to more-potent natural killer cells but also to effectors of lymphokine-activated killer (LAK) activity, although they do not express the Tac peptide. In the present study, using cross-linking methodology, we found that normal LGL and leukemic LGL from all individuals tested expressed the p75 IL-2 binding peptide but did not express the Tac peptide. These LGL leukemia cells made proliferative responses to IL-2 but required a much higher concentration than that required for the proliferation of normal phytohemagglutinin-stimulated T lymphoblasts that express high-affinity receptors. Furthermore, the addition of IL-2 to Tac-negative LGL leukemic cells augmented transcription of the Tac gene and induced the Tac peptide. Neither the IL-2-induced proliferation nor the up-regulation of Tac gene expression was inhibited by the addition of anti-Tac. These results strongly suggest that the p75 peptide is responsible for IL-2-induced activation of LGL and that the p75 peptide alone can mediate an IL-2 signal. Thus, the p75 peptide may play an important role in the IL-2-mediated immune response not only by participating with the Tac peptide in the formation of the high-affinity receptor complex on T cells but also by contributing to the initial triggering of LGL activation so that these cells become efficient natural killer and lymphokine-activated killer cells.

Cell Division↗

Evoked release of methionine enkephalin from tolerant/dependent enteric ganglia: paradoxical dependence on morphine.

Experiments were performed in order to determine whether the state of tolerance to and dependence upon opiates is associated with changes in one or more of the characteristics of the electrically induced release of methionine enkephalin from enteric ganglia. Acute morphine pretreatment substantially reduces the magnitude of the evoked release of this peptide from opiate-naive ilea. However, the rate of the evoked release of enkephalin from morphine-pretreated, tolerant/dependent preparations is indistinguishable from that observed for untreated, naive ilea. Paradoxically, 15 min after acute in vitro withdrawal of morphine form such preparations, the presence of morphine appears to be prerequisite for the manifestation of electrically evoked release of methionine enkephalin. The evoked release of this peptide from ilea 60 min after withdrawal is no longer dependent upon morphine. Moreover, the magnitude of the increase in the rate of enkephalin release from these preparations is almost double that observed for opiate-naive ilea. These data indicate that the manifestation of opiate tolerance/dependence for the release of methionine enkephalin from enteric ganglia comprises several adaptive processes, the consequences of which can be observed at different stages of withdrawal.

Animals↗

Immunoglobulin and T cell receptor gene rearrangements in human lymphoma and leukemia.

DNA samples from blood leukocytes or tumor biopsies of 45 patients with phenotypic B or T cell neoplasms were analyzed for rearrangements of the immunoglobulin (Ig) or T cell receptor (TCR) genes by Southern blot hybridization analysis. Rearrangements of the Ig heavy chain joining region genes (JH) were present in DNA from each of 28 B cell lymphomas and leukemias; 14 of 21 of these tumors also had rearrangements of the Ig kappa light chain joining (JK) or deleting element (KDel) genes. Conversely, 16 of 17 T cell lymphomas and leukemias had rearranged TCR beta chain genes. One B cell and one T cell tumor had rearrangements of both Ig and TCR genes. There was a strong correlation between the rearrangements of specific genes and the immunophenotype of the tumor: JH rearrangement without TCR beta chain rearrangement occurred only in B cell tumors; TCR beta chain rearrangement with or without JH rearrangement occurred only in T cell tumors, with one exception; and JK and KDel rearrangements were found only in B cell tumors. Thus, rearrangements of the Ig heavy and light chain genes and the TCR beta chain genes were found to be highly sensitive markers of monoclonal human lymphomas and lymphoid leukemias, with the type of gene rearrangements well correlated with the cell lineage of these neoplasms.

Antigens, Neoplasm↗

The distribution and ontogeny of MHC antigens in murine ocular tissue.

The distribution of H-2 (Class I) and Ia (Class II) antigens in the mouse eye was determined with the use of monoclonal antibodies and found to be different. H-2 antigen was observed in the corneal epithelium, conjunctival epithelium, choroid, and inner and outer nuclear layer of the retina--in order of decreased intensity of staining. In contrast, Ia was detected most strongly, in a patchy distribution, in the choroid, limbus epithelium, and peripheral corneal stroma, followed by the iris and ciliary body. Thus, distinctively different patterns of distribution of H-2 and Ia were observed in the normal mouse eye. Surprisingly, adult eyes stained more intensely for both H-2 and Ia antigens than neonatal eyes, implying that the expression of MHC antigens varies with ontogeny. Since unique and important immunologic functions have been ascribed to class I and II antigens, their different distribution within the eye may indicate that various ocular structures can play distinctive roles in the immune response.

Animals↗

Primary non-Hodgkin's lymphoma of the heart in two patients with the acquired immunodeficiency syndrome.

We report two cases of primary cardiac lymphoma that developed in patients suffering from the acquired immunodeficiency syndrome. Both cases of lymphoma were histologically aggressive as generally observed in patients with the acquired immunodeficiency syndrome. The lymphoma cells in the center of a tumor nodule obtained from one patient were monoclonal B-cells, whereas those at the periphery showed a polyclonal pattern of staining. It is postulated that this represents a monoclonal lymphoma evolving from a polyclonal B-cell lymphoproliferation analogous to those reported in some cases of lymphoma in immunosuppressed patients infected with Epstein-Barr virus. The lymphoma cells in the other case failed to stain for cytoplasmic immunoglobulins. The possible underlying basis for the increase in incidence of lymphoma in immunodeficiency and the reasons for prevalence of extranodal sites are discussed.

Acquired Immunodeficiency Syndrome↗

Phenotypic changes in large cell transformation of small cell lymphoid malignancies.

Large cell transformation of two cases of chronic lymphocytic leukemia and two cases of small lymphocytic lymphoma were studied. Changes in surface immunoglobulins were observed in two cases. In one case, there was a change from IgM to IgG. In another case, the large cells bore kappa light chains whereas the small cells had lambda light chains. Surface antigens other than immunoglobulin might also differ. All three small cell malignancies tested, but none of the large cell tumors, expressed the antigen T1 (Leu 1). The antigens HLA-DR, Leu 14, B1, and BA1 were expressed by both the small and large cell malignancies with one exception. The staining intensity might, however, change on transformation. The common acute lymphocytic leukemia antigen was not detected on any of the tumors studied and the expression of BA2 was variable. Surface marker studies cannot confidently distinguish between large cell lymphomas resulting from clonal evolution and those arising de novo. More definitive studies such as analyzing the idiotypic determinants on and amino acid sequences of the heavy and light chains or analyses of immunoglobulin gene rearrangements are necessary to confirm or exclude the same clonal origin in such cases.

Adult↗

Sequential testicular biopsies in childhood acute lymphocytic leukemia.

Between August 1978 and November 1981, 33 boys with acute lymphocytic leukemia (ALL) (26 non-T, 7 T-cell) younger than 16 years underwent bilateral wedge testicular biopsies at the time of initial diagnosis. Seven (4 non-T, 3 T-cell) demonstrated focal leukemic infiltrates. Rebiopsy after successful induction therapy without testicular irradiation showed eradication of leukemic infiltrates in five, persistent focal infiltrates in one, and a diffuse infiltrate in one. The two patients who had persistent leukemic involvement had a T-cell phenotype, and in one of them overt testicular disease developed 2 years later. All 33 patients were followed prospectively for a minimum of 3 years. Fifteen (14 non-T, 1 T-cell) remained in remission for 3 years and underwent another testicular biopsy before the cessation of therapy. Two patients, both non-T and both of whom were free of testicular involvement at diagnosis, showed testicular infiltrates at that time. Of the seven boys with positive specimens at diagnosis, only two remained disease-free for 3 years and showed no testicular involvement upon the completion of chemotherapy. In this study, microscopic testicular involvement by lymphoblasts occurred in 21% of newly diagnosed boys with ALL; this occurred only if the leukocyte count exceeded 25,000/microliter. These patients in general had a poor prognosis, probably reflecting the overall heavy tumor burden. However, it was not possible to predict accurately those patients who would have leukemic testicular infiltrates at the cessation of chemotherapy by performing biopsy of the testes at the time of initial diagnosis or after induction therapy.

Adolescent↗

Percutaneous needle biopsy in the diagnosis and classification of lymphoma.

Results of percutaneous needle biopsies were evaluated retrospectively in 58 patients in whom a diagnosis of lymphoma was suspected. The biopsy specimen was diagnostic in 94% of the 36 patients with lymphoma, 20 of whom had recurrent disease and 16 of whom had newly diagnosed lymphoma. Sufficient tissue was obtained in 94% of these positive biopsy specimens to allow histologic subtyping of the lymphoma. Immunohistochemical studies performed on seven of the biopsy specimens allowed immunologic subclassification into B-cell and T-cell types of lymphoma. Our results suggest that the percutaneous needle biopsy is a useful and reliable tool in the diagnosis and classification of lymphoma.

Adolescent↗

Human sympathetic ophthalmia. Immunologic analysis of the vitreous and uvea.

The inflammatory cell reaction within the vitreous and uvea of a human eye with atypical sympathetic ophthalmia was studied immunohistologically and with the fluorescence-activated cell sorter. The uveal infiltrate consisted predominantly of T cells of the helper/inducer subset, with less than 5% of the cells characterized as B cells, plasma cells, or monocytes. These results suggest that T cells perform an important role in atypical human sympathetic ophthalmia. A similar population of mononuclear cells was observed in the vitreous inflammatory infiltrate, in marked contrast to the peripheral blood, where there was a significant depression of circulating T cells. The similarity between the inflammatory cell populations within the vitreous cavity and uvea, in contrast to the peripheral blood, underlines the importance of studying the intraocular inflammatory reaction in uveitis to gain further insight into the mechanism of this disease.

Autoimmune Diseases↗

Lymph node interdigitating reticulum cell sarcoma.

A 67-year-old man presented with a malignant tumor involving abdominal lymph nodes, spleen, liver, and lungs, with associated protracted fever and night sweats. The tumor consisted of large pleomorphic cells, often surrounding microabscesses. Intracytoplasmic S100 protein, surface T6, Leu-3a (T4), and HLA-DR antigens were demonstrated. The malignant cells also possessed ATPase activity. Ultrastructurally, the cells exhibited numerous interdigitating cell processes but no Birbeck granules. The anatomic distribution of the tumor, its ultrastructural features, immunologic phenotype, and enzymatic profile are all consistent with a derivation from lymph node interdigitating reticulum cell. The tumor was unresponsive to the chemotherapeutic agents administered, and the patient soon died.

Adenosine Triphosphatases↗

Heterogeneity of large granular lymphocyte proliferations: delineation of two major subtypes.

Two major types of lymphocytosis of large granular lymphocytes (LGLs) were observed. The proliferating LGLs in each type had distinct immunophenotypes, functional characteristics, and probably belonged to different cell lineages. The more common form (Type A) consisted of cells derived from the T cell lineage and had the T suppressor/cytotoxic phenotype (T11+, T3+, T8+). The expression of the Leu 7 and HLA-DR antigen was variable. These cells did not have natural killer (NK) function but showed a variable degree of antibody-dependent cell-mediated cytotoxic (ADCC) activity. Neutropenia was invariably present and rheumatoid arthritis and autoantibodies were frequent associations. These lymphocytes had many similarities to the major type of LGLs present in normal adult bone marrow. The other type of LGL lymphocytosis (Type B) consisted of cells lacking the antigens T3 and T8 but expressing M1 and NKH1. These cells possessed strong NK and ADCC activity but their cell lineage was not clear. Neutropenia and autoimmune phenomena were not detected. The cytochemical characteristics of the LGL granules from both types of patients were similar but differences in ultrastructure were observed. LGLs from Type B patients proliferated in the presence of Interleukin 2 (IL-2) and 12-O-tetradecanoyl-phorbol-13 acetate (TPA). Significant changes in their basic T11+, T3-, T8- phenotype were not observed. IL-2 and TPA, however, had profound influence on the NK function of the cells with enhancement in the case of IL-2 and marked suppression when stimulated by TPA.

Adult↗

Spontaneous regression of a monoclonal proliferation of large granular lymphocytes associated with reversal of anemia and neutropenia.

A 43-year-old male with a phenotypically homogeneous, expanded subset of T cells presented in 1981 with anemia and neutropenia. The surface antigen phenotype of 99% of the peripheral blood lymphocytes was T3+, T8+, T4-, and they were morphologically large granular lymphocytes (LGL). The same cells comprised 37% of the marrow nucleated cells. Eight months after he presented, the peripheral blood T8+, LGL diminished spontaneously, and the anemia and neutropenia completely resolved. The patient remains hematologically normal as of October 1984. To determine if the T8+, LGL represented a clonal expansion, DNA from peripheral blood lymphocytes collected and cryopreserved when the patient was neutropenic and anemic, and when he was hematologically normal, was analyzed for clonal T-cell antigen receptor gene rearrangements. Using Southern blot analysis, a clonal DNA rearrangement was demonstrated, and this clone diminished but was still demonstrable in peripheral blood lymphocytes collected in 1984. The above observations implicate the expanded T8+, LGL in the pathogenesis of the neutropenia and anemia, yet the exact mechanism remains to be elucidated.

Adult↗

Direct analysis of the release of methionine-enkephalin from guinea pig myenteric plexus: modulation by endogenous opioids and exogenous morphine.

The in vitro release of methionine-enkephalin (met-enkephalin) from two longitudinal muscle myenteric plexus strips from guinea pig ileum has been obtained during continuous superfusion and quantitated directly using a radioimmunoassay specific for this opioid peptide. Electrical stimulation (5-80 Hz) produced a significant increase in the rate of release of met-enkephalin the magnitude of which was not dependent on the frequency of stimulation. Analysis of the release of met-enkephalin per pulse as a function of the frequency of stimulation indicated that the release of this opioid peptide from the myenteric plexus is inversely proportional to the frequency of stimulation. Electrically evoked release (40 Hz) of met-enkephalin was reduced by greater than 80% by substituting CoCl2 for CaCl2 or by pretreatment with tetrodotoxin (1 microgram/ml for 15 min). Evoked release was also reduced substantially by pretreatment with morphine (1 microM, 1.5 min). Alternatively, pretreatment of naive longitudinal muscle myenteric plexus strips with the opiate antagonist (-)-naloxone caused a significant increase in the rate of met-enkephalin release in the absence of electrical stimulation. In contrast, (+)-naloxone was devoid of any activity. These data, in combination with indirect pharmacological experiments, strongly indicate that met-enkephalin functions as a neurotransmitter in the enteric nervous system. Moreover, the activity of neurons that transmit via met-enkephalin appears to be under opioid regulation.

Animals↗

T-cell lymphoma following Hodgkin's disease.

Three patients initially diagnosed with Hodgkin's disease developed non-Hodgkin's lymphoma 1.5, 7, and 16 years later, respectively. Combined modality therapy had been employed in one patient; the other two had received combination chemotherapy. All three of the second neoplasms were morphologically characterized as peripheral T-cell lymphomas. Cell surface marker studies performed on two of these tumors confirmed their T-cell origin. Second lymphoproliferative malignancies are an increasingly recognized complication in patients with Hodgkin's disease. Further immunologic phenotyping is needed to more conclusively define the origin and frequency of occurrence of these tumors.

Adolescent↗

Increase in high-grade lymphomas in young men.

The relative frequencies of non-Hodgkin's lymphoma (NHL) subtypes and primary sites of presentation in young men before and during the acquired immunodeficiency syndrome epidemic were studied. Diagnostic pathological specimens were reviewed and classified according to the Working Formulation grades for cases of NHL in men aged 20-49 years identified through a population-based cancer registry. 76% of the lymphomas diagnosed in 1981-82 were intermediate or high grade, compared with 29% of those diagnosed in 1976-77. This increase was still significant when men aged 20-39 years and 40-49 years were grouped separately, and for married men. The proportion of extranodal lymphomas diagnosed in men aged 20-39 years also rose significantly from the early to the later period.

Acquired Immunodeficiency Syndrome↗