Biomedical subjects

N L Harris

Publications and source records attributed to N L Harris.

At least 163 records · Page 9Linked to original sources

PubMed1989

Hodgkin's disease and Epstein-Barr virus. Altered antibody pattern before diagnosis.

In patients with Hodgkin's disease, titers of IgG antibody against viral capsid antigen of Epstein-Barr virus and the prevalence of antibodies against early antigen are higher than expected. To evaluate whether this condition antedates diagnosis, we identified 43 persons with Hodgkin's disease, from whom blood had been drawn and stored for an average of 50.5 months before diagnosis, and 96 controls from the same populations, from whom blood had been drawn at the same time. The relative risks of Hodgkin's disease associated with elevated levels of IgG and IgA antibodies against capsid antigen were 2.6 (90 percent confidence interval, 1.1 to 6.1) and 3.7 (1.4 to 9.3), respectively. For Epstein-Barr nuclear antigen, the relative risk was 4.0 (1.4 to 11.4), and for early antigen D it was 2.6 (1.1 to 6.1). However, the prevalence of IgM antibody against capsid antigen was substantially lower in patients with Hodgkin's disease (0.22 [0.04 to 1.3]). These associations were stronger in serum samples obtained at least three years before diagnosis than in serum samples obtained closer to diagnosis. We conclude that the development of Hodgkin's disease may in some patients be preceded by enhanced activation of Epstein-Barr virus. Whether Epstein-Barr virus has a direct role in the pathogenesis of the disease or is simply a marker for a more fundamental factor affecting the immune control of latent infections is unknown.

Antibodies, Viral↗

PubMed1989

Humoral hypercalcemia in Hodgkin's disease. Clinical and laboratory evaluation.

To provide further understanding of humoral hypercalcemia in Hodgkin's disease (HD) the authors describe the clinical features and laboratory investigation of three patients recently treated at Massachusetts General Hospital. All were middle-aged men who presented with symptomatic hypercalcemia which led to a diagnosis of bulky intraabdominal HD. None had evidence of bone involvement or hyperparathyroidism. In the two cases tested 1,25(OH)2D3 was elevated at the time of diagnosis. These characteristics are remarkably similar to those of ten patients with HD and probable humoral hypercalcemia described in the literature. The diagnosis of HD was supported in Cases 1 and 3 by genomic blot analysis which showed no evidence of T-cell or B-cell tumor origin. In an in vitro assay, primary tumor medium from Case 1 stimulated dose-dependent bone resorption which was not entirely ascribable to 1,25(OH)2D3. The authors conclude that humoral hypercalcemia in HD predominantly affects males of middle age, that intraabdominal bulky disease is common, and that hypercalcemia appears to be mediated by tumor related production of 1,25(OH)2D3 in concert with a second factor.

Adult↗

PubMed1989

Lupus lymphadenitis: report of a case with immunohistologic studies on frozen sections.

A case of lupus lymphadenitis with frozen section immunohistologic studies is presented. Clinically, the patient had well-documented systemic lupus erythematosus (SLE) when rapid development of generalized lymphadenopathy raised the possibility of a diagnosis of malignant lymphoma. Histologically, the findings of paracortical foci of necrosis and hematoxylin bodies were diagnostic of SLE. Granulocytes were absent. Monoclonal antibodies applied to frozen sections demonstrated two predominant cell populations within and surrounding the paracortical zones of necrosis: OKM1+, Leu-M1+ histiocytes and OKT8+, Leu-4+ T cytotoxic/suppressor cells. In the lymph node not involved by necrosis, lymphoid follicles were composed of polytypic B cells and the interfollicular regions of T cells. Leu-3a+, Leu-4+ T helper/inducer cells outnumbered T cytotoxic/suppressor cells in a 3:1 ratio. Since lupus lymphadenitis may closely resemble histiocytic necrotizing lymphadenitis of Kikuchi and Fujimoto, particularly if hematoxylin bodies are not found, we compared the findings in this case with findings of cases of histiocytic necrotizing lymphadenitis of Kikuchi and Fujimoto reported in the literature. The immunologic findings in both diseases are similar. We conclude that immunologic studies using frozen sections are probably of no help in differentiating between these two disorders when histologic findings are not conclusive.

Adult↗

PubMed1989

Lymphoid infiltrates of the orbit and conjunctiva. A morphologic and immunophenotypic study of 99 cases.

Most of the earlier clinicopathologic studies of orbital and conjunctival lymphoid infiltrates were done before the development of immunohistologic methods. In this study, we have examined 99 lymphoid infiltrates of the orbit and conjunctiva immunohistologically and correlated clinical and histologic features with immunophenotype. Sixty-six infiltrates expressed monotypic immunoglobulin; one case was immunoglobulin-negative, B-lineage; and 32 infiltrates expressed polytypic immunoglobulin. Using histologic criteria, 36 cases were malignant (35 monotypic; one immunoglobulin-negative, B-lineage), 44 were indeterminate (31 monotypic, 13 polytypic), and 19 were benign (all polytypic). Combining histologic and immunophenotypic criteria, 67 cases were diagnosed as malignant lymphoma. Seventy-six percent of the lymphomas were classified as low-grade according to the Working Formulation; small lymphocytic lymphoma (45%) was the most common histologic subtype. Cytologic atypia (p less than .0001) and Dutcher bodies (p less than .05) were found only in lymphomas. Similarly, bilateral involvement (p less than .05) and dissemination at time of presentation (p less than .001) occurred only in lymphomas. No other histologic or clinical features reliably distinguished lymphomas from benign orbital and conjunctival lymphoid infiltrates. Nineteen patients had a prior history of extraorbital malignant lymphoma, and eight patients had a history of pseudolymphoma. Patients with a history of malignant lymphoma more often presented with dissemination (p less than .001) and less often had the small lymphocytic subtype (p = .07) than patients without a history of lymphoma. However, not all patients with a history of extraorbital lymphoma had monotypic orbital and conjunctival infiltrates, and the incidence of monotypic orbital and conjunctival lesions in these patients was similar to that of the patients without a history of lymphoma. Patients with a history of pseudolymphoma always presented with localized disease (p less than .01) and more often had benign lesions (p = .08) as compared with patients without a history of pseudolymphoma. We conclude that the presence of either cytologic atypia or Dutcher bodies is a reliable criterion of malignant lymphoma in the orbit and conjunctiva. However, for one-third of the cases in this study, immunohistologic studies were the only means of distinguishing malignant from benign lymphoid infiltrates.

Conjunctiva↗

PubMed1989

Primary large cell lymphoma of the mediastinum. A histologic and immunophenotypic study of 29 cases.

We studied the morphologic and immunologic features of 29 cases of primary nonlymphoblastic non-Hodgkin's lymphoma of the mediastinum. The patients ranged in age from 15 to 73 years, with a median of 32 years. The mean age for the 11 men (50 years) was significantly higher than that for the 18 women (32 years) (p less than 0.05). All had diffuse large cell lymphomas (six immunoblastic, 14 large cell not otherwise specified, six large cell noncleaved, one large cell cleaved, and two not subclassifiable). Sclerosis was prominent in 11 cases, none of them immunoblastic, and did not correlate with superior vena cava syndrome. The mean age (54 years) of patients with immunoblastic lymphomas was higher than that for patients with other subtypes (35 years) (p less than 0.02). Frozen-section immunoperoxidase staining disclosed monotypic immunoglobulin in 13 cases, with a high frequency of heavy-chain class switching (seven IgG, two IgA, four IgM). Sixteen cases were immunoglobulin negative; 14 of 15 cases expressed B-lineage antigens, and none expressed T-lineage antigens. Three of four cases showed immunoglobulin heavy- or light-chain gene rearrangement by the Southern blot technique. None showed rearrangement of the T-cell receptor beta-chain-gene constant region. There was no correlation between immunophenotype and morphologic subtype. The immunoglobulin-negative group was predominantly female (13 of 16 cases; p less than 0.02), and younger (mean age, 34 years versus 44 years; p = NS) than the immunoglobulin-positive group; however, the difference in age was not statistically significant. The actuarial 5-year survival was 57%, and there was no correlation between survival and either histologic subtype or immunophenotype. Mediastinal large cell lymphoma is a B-cell tumor, which frequently lacks immunoglobulin, may be primary in the thymus, has a predilection for young women, and can be cured with aggressive therapy.

Adolescent↗

PubMed1989

Uterine leiomyomas with lymphoid infiltration simulating lymphoma. A report of seven cases.

Seven women, 35-50 years of age, had uterine leiomyomas with lymphoid infiltration. The leiomyomas ranged from 2 to 12 cm in greatest dimension and contained a variably dense infiltrate of small lymphocytes with scattered larger lymphoid cells and occasionally, numerous plasma cells; germinal centers were identified in some cases and ranged from large and florid to inconspicuous; rarely, eosinophils were present. Most of the tumors contained focal to extensive areas of sclerosis. In all the cases in which adjacent myometrium was available for examination, the lymphoid infiltrate was confined to the leiomyoma or was present to only a minor extent in the adjacent myometrium. Significant lymphoid infiltration of uterine leiomyomas, which appears to be a reactive process, has not been described previously. The polymorphous nature of the infiltrate and its confinement to the leiomyoma distinguish it from malignant lymphoma.

Adult↗

PubMed1989

Uveal lymphoid infiltrates: immunohistochemical evidence for a lymphoid neoplasia.

A 67-year-old man presented with a diffuse choroidal and ciliary body infiltrate, suggesting clinically and ultrasonographically a diffuse uveal melanoma. After enucleation both morphological and immunohistochemical data were highly suggestive of a diffuse, low-grade B cell lymphoma or lymphoplasmacytic immunocytoma. The difficulties of clinical and histopathological differential diagnosis of uveal lymphoid infiltrates are emphasised. In view of the excellent life prognosis of these tumours, treatment of the patient should be directed towards the preservation of ocular function.

Aged↗

PubMed1989

Detection of Epstein-Barr virus in CNS lymphomas by in-situ hybridization.

We used an optimized in-situ hybridization technique employing a biotinylated Epstein-Barr (EB) virus sequence, BamH1V (3.1 kb), to detect this sequence in 2 EB virus-infected cell lines (B95-8 and Namalwa) and 8 CNS lymphomas. We obtained a good hybridization signal from cytospins of B95-8 (EB virus productively infected) and Namalwa (EB virus latently infected, 1 copy per cell) cell lines. We were able to detect signal from both cell lines after overnight fixation in 10% formalin and paraffin embedding, but development time in the detection chromogen required longer incubation and the signal intensity was lower than in cytospin cells. We then used the technique to examine formalin-fixed, paraffin-embedded primary CNS lymphoma tissue from 4 patients who were immunocompromised (1 renal transplant, 3 acquired immune deficiency syndrome) and 4 patients who were not. All 4 CNS lymphomas from immunocompromised patients hybridized well with BamH1V, exhibiting a pattern of staining similar to Namalwa cells and nonlytically infected B95-8 cells. There was no relationship between the intensity and degree of reaction and the patients' survival. None of the 4 CNS lymphomas in immunocompetent patients or uninvolved brain showed any reactivity with BamH1V. We suggest that low-abundance targets are detectable in paraffin-embedded tissue by in-situ hybridization using biotinylated probes. Detection of EB viral sequences in CNS lymphomas in immunocompromised patients suggests a role for the virus in the pathogenesis of this tumor.

Acquired Immunodeficiency Syndrome↗

PubMed1989

The clinical relevance of lymphocyte marker studies in the diagnosis of lymphoma.

Immunologic analysis has greatly improved diagnostic accuracy in several clinically important areas, however, the ultimate goal of a lymphoma classification based on immunophenotype has not been reached and may not be forthcoming. In the evaluation of a patient suspected of having lymphoma, lymphocyte marker studies may be essential for a correct diagnosis, helpful but not essential, or entirely noncontributory, depending on the specific clinical setting and histological differential diagnosis. This review will cover the basic principles and technical aspects of marker studies, and will explore several problems in differential diagnosis to clarify the role of marker studies in determining patient management.

Antigens, Neoplasm↗

PubMed1989

Lymphoproliferative disorders and hematologic malignancies following organ transplantation.

Eleven allograft recipients (one cardiac, one hepatic, nine renal) at the Massachusetts General Hospital developed a lymphoproliferative disorder or leukemia. Six (all renal) patients received conventional immunosuppressive therapy (CIT), four received cyclosporin A (CsA) (one cardiac, one hepatic, two renal), and one received CIT for his first transplant and CsA for his second transplant (both renal). The interval from transplant to onset of the hematologic disorder ranged from 2 mo to 3 yr in the CsA group and from 6 mo to 9 yr in the CIT group and was 16 yr in the patient with two allografts. There were eight malignant lymphomas, seven of which were extranodal, (four immunoblastic, one large noncleaved cell, one small noncleaved cell, one plasmacytoma, one unclassifiable), one case of polymorphic diffuse B cell hyperplasia and two cases of acute myeloid leukemia. Frozen section immunohistochemistry in six cases showed monotypic immunoglobulin in four lymphomas, (including the plasmacytoma), an immunoglobulin-negative B cell phenotype in one lymphoma, and polytypic immunoglobulin in the case of polymorphic hyperplasia. One lymphoma showed a monotypic immunoglobulin-producing B cell population in one site and an immunoglobulin-negative B cell population in another site. With an immunoglobulin heavy chain gene-specific probe, Southern blot analysis of tissue from these two sites revealed two distinct rearrangements. When tissue from a second case of lymphoma was analyzed by Southern blot, identical rearrangements of the heavy chain gene were found in tumor from two separate sites. Similar to the experience of others, we find an increased incidence of lymphoma and a slightly increased incidence of acute myeloid leukemia in allograft recipients. In contrast to other reports, we found a predominance of monoclonal B cell malignancies, a more polymorphous histologic appearance of the lymphoproliferative disorders in CsA patients, and one case each of "multiclonal" and "monoclonal" lymphomas when tumor from separate sites was tested for gene rearrangement.

Adolescent↗

PubMed1988

Mediastinal large cell lymphoma. An uncommon subset of adult lymphoma curable with combined modality therapy.

Thirty adults with large cell lymphoma predominantly localized to the mediastinum diagnosed at the Massachusetts General Hospital between 1976 and 1985 were identified. The median age of the 20 females and 10 males was 34 years. All but one presented with symptoms due to an enlarging mediastinal mass, which was localized in 22 patients (73%) and exceeded 10 cm in maximal diameter in 65%. Superior vena cava syndrome and large pleural and pericardial effusions were common. Employing CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) and consolidation radiation therapy in most cases, 80% achieved a complete remission and 59% survive failure-free at 5 years by actuarial calculation. The size of the mediastinal mass adversely affected failure-free survival (89% vs. 40%, P less than 0.05). No other pretreatment risk factor predicted outcome, but more intense chemotherapy was associated with improved survival (P = 0.035). Large cell mediastinal lymphoma is a locally invasive, often bulky malignancy with a predilection for young women; disease of low or moderate bulk is curable with full dose CHOP chemotherapy and consolidation radiation, but bulky disease requires more aggressive treatment.

Adolescent↗

PubMed1988

The influence of ranitidine on the pharmacokinetics and toxicity of doxorubicin in rabbits.

The influence of ranitidine on the pharmacokinetics and toxicity of doxorubicin was studied in six female New Zealand white rabbits. Plasma pharmacokinetic data were first obtained from rabbits given 3 mg/kg doxorubicin. After 1 month, the same rabbits were treated with ranitidine, 2.5 mg/kg or 25 mg/kg, before and during doxorubicin administration. The plasma doxorubicin assays to determine pharmacokinetic parameters were repeated. Drug toxicity was evaluated using complete blood counts, and hepatic function was measured using a 14C-aminopyrine breath test. High-dose ranitidine increased the total exposure to doxorubicin (area under the curve of doxorubicin alone = 1.44 +/- 0.88 microM.h/ml vs 4.49 +/- 2.35 microM.hr/ml for doxorubicin given with high-dose ranitidine; P = 0.06). Low-dose ranitidine did not alter doxorubicin pharmacokinetics. Exposure to doxorubicinol was altered by either high-dose or low-dose ranitidine. 14C-Aminopyrine half-life was altered by a ranitidine dose of 25 mg/kg (aminopyrine half-life after placebo control = 97 +/- 6 min as against aminopyrine half-life after ranitidine = 121 +/- 7 min; mean +/- SEM; P less than 0.02). Low-dose ranitidine did not exacerbate doxorubicin-induced myelosuppression. High-dose ranitidine enhanced doxorubicin-induced erythroid suppression while sparing the myeloid series. At cytochrome P-450-inhibitory doses, ranitidine's effects upon doxorubicin plasma pharmacokinetics are similar to those previously seen with cimetidine. These changes did not appear to alter drug detoxification and are not related to microsomal inhibition of doxorubicin detoxification. Low doses of ranitidine do not alter doxorubicin plasma pharmacokinetics or toxicity in rabbits.

Aminopyrine↗

PubMed1988

Computed tomography in the evaluation of lymphoma of the uterine cervix.

Primary involvement of the uterine cervix is a rare presentation of extranodal lymphoma. The clinical and computed tomography findings are described in four patients ranging from 23 to 74 years of age. All presented with vaginal bleeding. Computed tomography findings were similar to those of other primary pelvic neoplasms, with diffuse uterine enlargement and lobular contour alteration often mimicking fibroids. Lymphadenopathy was not observed in comparison to secondary lymphoma of the female genitalia. All patients had excisional biopsies. One patient had an initial TAH and BSO. Histology was varied with one case of large cell lymphoma, one of diffuse histiocytic, one of unclassifiable poorly differentiated lymphoma, and one of nodular poorly differentiated lymphocytic lymphoma that was finally classified as granulocytic sarcoma. Disease extent could be assessed by computed tomography and aided treatment planning. In conclusion, computed tomography was found to be useful in the evaluation of uterine lymphoma. Although the findings are not specific, the local tumor extent can be evaluated at the same time as other sites of potential involvement.

Adult↗

PubMed1988

Intravascular lymphomatosis (malignant angioendotheliomatosis). A B-cell neoplasm expressing surface homing receptors.

We report the clinical and immunohistochemical features of six cases of intravascular lymphomatosis. All patients presented with symptoms referable to central nervous system (CNS) involvement. In two patients, the diagnosis was made on brain biopsy specimens. In the remaining four cases, diagnosis was made at autopsy. Three of the four autopsied patients had focal extravascular lymphoma, diffuse large cell type. In all five cases tested, immunohistochemical stains on paraffin-embedded sections confirmed the lymphoid nature of the malignant cells. Stains on frozen sections in one case, and on paraffin-embedded tissue in the other four cases, demonstrated B-lymphocyte lineage. In the remaining case, electron microscopy confirmed the lymphoid nature of the tumor cells. All three cases tested expressed the Hermes 3-defined homing receptor antigen and lacked peanut agglutinin receptors. Our results are consistent with other reports confirming the lymphoid nature of so-called malignant angioendotheliomatosis. Our limited analysis of surface receptor molecules suggests that the expression of the homing receptor for high endothelial venules is not in itself responsible for the unusual intravascular location of these cells.

Aged↗

PubMed1987

Effect of allyl alcohol-induced sublethal hepatic damage upon doxorubicin metabolism and toxicity in the rabbit.

A model of hepatic dysfunction in vivo has been developed in rabbits to determine the effects of sublethal hepatocellular necrosis upon doxorubicin pharmacology. Eight New Zealand white rabbits were given 3 mg/kg doxorubicin i.v. Plasma doxorubicin and metabolite pharmacokinetics were determined and toxicity assessed by nadir complete blood counts. Hepatic function was assessed by the pulmonary excretion rate of 14CO2 from [14C]aminopyrine. Hepatocellular necrosis was produced by i.v. injection of 1.35 mg/kg of a 2% allyl alcohol solution. Doxorubicin administration and pharmacokinetics were repeated. Doxorubicin enhances the hepatotoxicity of allyl alcohol. Hepatocellular necrosis does not alter the plasma pharmacokinetics of doxorubicin but does increase the plasma exposure of doxorubicinol. Doxorubicin-induced myelosuppression is enhanced by allyl alcohol pretreatment. These data suggest that in circumstances of reduced hepatocellular volume or acute hepatocellular necrosis, a key plasma marker of doxorubicin-induced acute toxicity may be doxorubicinol.

1-Propanol↗

PubMed1987

Immunoglobulin gene rearrangements in adult non-Hodgkin's lymphoma.

Southern blotting was employed to analyze the immunoglobulin heavy and light chain genes and the gene for the T cell receptor beta chain in genomic DNA derived from the tumor specimens of 120 adults with pathologically classified and immunotyped non-Hodgkin's lymphoma and B cell chronic lymphocytic leukemia. In a consecutive series of 100 patients, one or two rearranged heavy chain genes could be detected in each of the 80 samples expressing clonal surface immunoglobulin. The kappa gene was rearranged in 70 percent of kappa-bearing tumors and in 23 percent of lambda-bearing specimens. Furthermore, a rearranged immunoglobulin gene was also observed in 21 of 29 lymphomas (nine from the consecutive series and 20 selected for surface immunoglobulin-negative status) in which B cell lineage was in doubt because of absent clonal surface immunoglobulin. These findings indicate that most cases of lymphoma and lymphocytic leukemia in adults are of B cell lineage, even when phenotypic evidence is inconclusive. The exceptional cases (only 3 percent in the consecutive series) were of either follicular lymphoma or diffuse large cell (histiocytic) lymphoma subtype; the lineage in cases of diffuse lymphocytic lymphoma or chronic lymphocytic leukemia was never in doubt. Although the convenience of surface marker analysis assures its continuing clinical application, gene study resolves indeterminate cases and extends the understanding of the pathogenesis of lymphoproliferative disease.

Adult↗

PubMed1987

"Plasmacytoid T cells" in Castleman's disease. Immunohistologic phenotype.

Plasmacytoid T cells in two cases of Castleman's disease were stained with a panel of monoclonal antibodies to hematopoietic cell-associated antigens, using an immunoperoxidase technique on frozen sections. The immunohistologic phenotype of these cells was T4/Leu-3+, HLA-DR+, T1/Leu-1-, T3/Leu-4-, T8/Leu-2-, T11/Leu-5-, B1-, B2-, Leu-14-, Ig-, CALLA-, OKM1-, Leu-M1-. In contrast to plasma cells of B lineage, plasmacytoid T cells were T200+, T10-. The phenotype was similar to that of two previously reported lymphomas of plasmacytoid T cells. Plasmacytoid T cells appear to be a unique subset of lymphoid cells, whose function remains to be established.

Adolescent↗

PubMed1987

Kimura's disease and angiolymphoid hyperplasia with eosinophilia: two distinct histopathological entities.

The relationship between the disorder known in Japanese and Chinese literature as Kimura's disease and that known in Western literature as angiolymphoid hyperplasia with eosinophilia (ALHE) has been the subject of debate. Many reports have used the terms synonymously. We have reviewed the histological and clinical features of 4 cases, all occurring in Caucasians, 2 of which are typical of Kimura's disease and 2 of ALHE. Analysis of the cases indicates that the histological features of the 2 disorders are sufficiently different to warrant their recognition as 2 distinct entities. The histological and clinical features of Kimura's disease are most consistent with an allergic or autoimmune process in which blood vessels, lymphocytes and eosinophils participate. Those of ALHE suggest a primary, probably neoplastic disorder of vascular endothelium with a variable and secondary inflammatory response. Although there is some clinical overlap between patients with the 2 disorders, the histological features are distinctive, and the 2 terms should not be used synonymously.

Adult↗