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Biomedical subjects

N L Harris

Publications and source records attributed to N L Harris.

At least 127 records · Page 7Linked to original sources

Immunohistochemical characterization of intraepithelial and subepithelial mononuclear cells of the upper airways.

The upper airway is the first site of exposure to inhaled antigens and the site of initiation of mucosal immunity to certain antigens; however, the intraepithelial lymphoid populations of this region have not been well characterized. We studied 6-mu frozen tissue sections from tonsils, adenoids, and nasal mucosae using immunohistochemistry and a panel of antibodies to mononuclear antigens to determine whether nasal mucosa contained distinctive populations of mononuclear cells. Intraepithelial lymphocytes (IELs) of nasal mucosa were CD3+, CD8+, and mainly CD5+. Tonsil and adenoid both showed diffuse CD8+ IELs; clusters of CD4+ IELs were associated with B cells within the crypt epithelium. All nasal IELs were uniformly negative for Leu8 (homing receptor analog of Mel14). Scattered Leu8-positive cells were present within tonsil and adenoid crypt epithelium only. Nasal IELs rarely expressed HML1 and were often CD7-, whereas the majority of tonsillar and adenoidal IELs were HML1+ and variably CD7+. In nasal mucosa and in deep submucosa of tonsil and adenoid, 80 to 90% of T cell receptor expression was of alpha/beta type. There was a concentration of gamma/delta T cell receptor-positive cells in intraepithelial and subepithelial zones of tonsil and adenoid, with areas of up to 30% gamma/delta T cell receptor positivity. A population of intraepithelial dendritic cells was identified in all three tissues expressing mononuclear phagocyte system antigens CD14 and KiM1P, but lacking CD1a. Virtually no B cells and no organized subepithelial lymphoid tissue were identified in nasal mucosa. Nasal mucosal lymphoid tissue seems to differ from that of endodermally derived mucosae, tonsil, and adenoids to share similarities with both mucosa-associated lymphoid tissue and peripheral lymph nodes.

Adenoids↗

Breast lymphoma. A B-cell spectrum including the low grade B-cell lymphoma of mucosa associated lymphoid tissue.

We studied the morphologic, immunologic, and clinical features of 31 cases of malignant lymphoma involving the breast. Primary breast lymphoma occurred in nine women with a median age of 69 years (range, 51-87 years); median follow-up was 31 months (range, 9-67 months). Eight cases were low grade, one was high grade, and all expressed B-lineage antigens. Four cases had features of lymphoma of mucosa-associated lymphoid tissue (MALT); three were free of disease after excision alone at 10, 12, and 48 months, whereas the fourth relapsed with transition to immunoblastic lymphoma and died at 25 months. Four patients had follicular lymphomas, three of which relapsed, causing death from active disease at a median of 55 months (range, 25-67 months). One case of small noncleaved cell lymphoma relapsed, causing death at 31 months. Lymphoma secondarily involved the breast in 22 patients (21 women, one man) with a median age of 60 years (range, 39-83 years) at breast relapse; these patients were followed for a median of 88 months (range, 2-271 months) from primary diagnosis and 4 months (range, 0-116 months) from breast relapse. Nineteen patients had prior documented lymphomas (10 nodal or splenic, nine extranodal), and breast involvement most commonly occurred as part of widespread, predominantly nodal disease. Three patients had breast involvement by lymphomas that were generalized at diagnosis or staging. Thirteen cases were low grade (nine follicular), seven intermediate grade, and one high grade; 19 of 20 cases expressed B-lineage antigens, and one expressed T-lineage antigens. Four cases had features of MALT-type lymphoma; in these patients, isolated breast relapses were interspersed with other extranodal relapses, with interim resolution of disease after local or systemic therapy; two were free of disease and two were alive with localized disease on treatment at median follow-up of 60 months (range, 9-91 months). In contrast, 15 of 18 nonMALT lymphomas had widespread disease at breast relapse (median, 29 months; range, 0-259 months); 16 of 18 received systemic therapy, 10 died with active disease, and five of eight had disseminated active disease at last follow-up. Primary breast lymphomas were commonly low grade. The follicular lymphomas had clinical behavior similar to nodal follicular lymphoma. Primary MALT-type lymphomas were a distinct subset with a potential for disease-free survival after local therapy. Secondary breast lymphomas were heterogeneous and more commonly higher grade, although follicular lymphoma was the most common subtype.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Primary lymphoma of the trachea with morphologic and immunophenotypic characteristics of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue.

A patient with primary extranodal lymphoma arising in the trachea presented with severe upper airway obstruction. The tumor was localized at presentation. The patient has remained disease-free for 12 months following surgical resection and local radiation treatment. The tumor had distinctive morphologic features characteristic of low-grade lymphomas of mucosa-associated lymphoid tissue (MALT), including a diffuse infiltrate of small lymphocytes and centrocyte-like cells surrounding reactive follicles, with plasmacytoid differentiation, and lymphoepithelial lesions. The tumor cells expressed monotypic immunoglobulin but not CD5 or CD10. This case provides evidence that primary lymphomas of the trachea in some cases are tumors of mucosa-associated lymphoid tissue.

Aged↗

Prethymic adult lymphoblastic lymphoma. A clinicopathologic and immunohistochemical analysis.

The clinical, histologic, and immunohistologic features of three cases of pre-T-cell (CD7+/CD2-) lymphoblastic lymphoma in adults are reported. The patients were adults over age 50 years who had a relatively indolent nodal disease, partial involvement of lymph nodes, and primitive immunophenotype. The phenotype of the three cases was TdT+, HLA-DR+, CD34+, CD71+, CD38+, and CD7+, most resembling the normal prothymocyte, and in contrast to normal thymocytes, which generally coexpress CD1+, CD4+, and CD8+. The prethymic T-cell character was further supported by germline T-cell receptor beta and gamma chain genes. In contrast to most reported cases with this early immunophenotype, these patients had nodal disease but not peripheral blood involvement. Two of the three cases were associated with Langerhans' cell histiocytosis (histiocytosis X), a previously unreported association. Because of the Langerhans' cell histiocytosis and the relatively indolent clinical presentation, the differential diagnosis in all cases included both a benign process and a lower-grade lymphoma. Recognition of this unusual form of adult lymphoblastic lymphoma is essential for correct diagnosis and treatment.

Aged↗

The relationship between Hodgkin's disease and non-Hodgkin's lymphoma.

The final Workshop of the meeting focused on cases of Hodgkin's disease (HD) in combination with non-Hodgkin's lymphoma (NHL), either T, B, or anaplastic large cell (ALC) type. The cases selected for this session fell into five categories: nodular lymphocyte-predominance Hodgkin's disease (NLPHD) with NHL, B cell chronic lymphocytic leukemia (CLL) with HD-like transformation, follicular lymphoma (FL) with HD or anaplastic large cell lymphoma (ALCL) (composite or discordant), HD following mycosis fungoides (MF), and HD following ALCL. Taken together, these cases left the participants with the distinct impression that there is likely to be some biological relationship between HD and a variety of T cell and B cell NHL.

Hodgkin Disease↗

Florid progressive transformation of germinal centers. A syndrome affecting young men, without early progression to nodular lymphocyte predominance Hodgkin's disease.

Progressive transformation of germinal centers (PTGC) occurs focally in reactive lymph nodes, and has been reported with increased frequency in patients with nodular lymphocyte predominance Hodgkin's disease (NLPHD). It has been suggested that patients with lymph node biopsy samples showing PTGC are at increased risk for the development of NLPHD, and that Hodgkin's disease may evolve from PTGC. We report five young men (ages 14-24 years, mean 18) with prominent lymphadenopathy and florid PTGC, in whom careful examination and follow-up showed no progression to Hodgkin's disease. Three patients developed adenopathy that involved several node groups and two had localized adenopathy. Cervical (2), inguinal (2) and axillary (1) nodes ranging from 3 to 4 cm were excised. The number of progressively transformed germinal centers (PTGCs) ranged from 10 to 123 per specimen (mean 67); single sections contained nine to 29 PTGCs (mean 19). In three cases the nodal architecture was significantly distorted, suggestive of NLPHD, but Reed-Sternberg cells were absent. Follow-up is available for all patients (all untreated): three patients had persistent adenopathy 1 year 4 months to 10 years after diagnosis. Results of repeat biopsy in two patients (2 and 3 years after diagnosis) showed florid PTGC with no evidence of Hodgkin's disease. One of these patients had one subsequent biopsy 8 years after presentation; results showed only rare PTGCs. The fourth and fifth patients, who had presented with isolated adenopathy, were free of recurrent adenopathy at 2 and 5 years. These cases suggest a syndrome of lymphoid hyperplasia with florid PTGC in adolescent boys and young men. Although adenopathy can persist, there has been no progression to Hodgkin's disease. Recognition of this syndrome is important to avoid overdiagnosis of LPHD. Close follow-up of these patients will be necessary to evaluate the relationship of this disorder to NLPHD.

Adolescent↗

The Rancho mounting technique for the Ilizarov method. A preliminary report.

To improve implant tolerance and muscle function associated with circular external fixation, the authors substituted divergent titanium pins for the tensioned steel wires used to mount the Ilizarov apparatus on a limb. The first ten patients treated with half-pins were compared to the last ten patients managed with tensioned wires. While the conditions were not exactly comparable, the half-pin group showed improvement over the wire group in categories including time in fixation, implant-site sepsis, range of joint motion, pain medication requirements, and ambulatory capacity. Half-pin mountings require special techniques for a successful application.

Adolescent↗

PRAD1, a candidate BCL1 oncogene: mapping and expression in centrocytic lymphoma.

Rearrangement of the BCL1 (B-cell lymphoma 1) region on chromosome 11q13 appears to be highly characteristic of centrocytic lymphoma and also is found infrequently in other B-cell neoplasms. Rearrangement is thought to deregulate a nearby protooncogene, but transcribed sequences in the immediate vicinity of BCL1 breakpoints had not been identified. PRAD1, previously designated D11S287E, was identified on 11q13 as a chromosomal breakpoint region rearranged with the parathyroid hormone gene in a subset of parathyroid adenomas; this highly conserved putative oncogene, which encodes a novel cyclin, has been linked to BCL1 and implicated also in subsets of breast and squamous cell neoplasms with 11q13 amplification. We report pulsed-field gel electrophoresis data showing BCL1 and PRAD1 to be no more than 130 kilobases apart. PRAD1 mRNA is abundantly expressed in seven of seven centrocytic lymphomas (Kiel classification), in contrast to 13 closely related but noncentrocytic lymphomas. Three of the seven centrocytic lymphomas had detectable BCL1 DNA rearrangement. Also, two unusual cases of CLL with BCL1 rearrangement overexpressed PRAD1, in contrast to five CLL controls. Thus, PRAD1 is an excellent candidate "BCL1 oncogene." Its overexpression may be a key consequence of rearrangement of the BCL1 vicinity in B-cell neoplasms and a unifying pathogenetic feature in centrocytic lymphoma.

Chromosomes, Human, Pair 11↗

Epstein-Barr virus antibody patterns preceding the diagnosis of non-Hodgkin's lymphoma.

Immunosuppressed patients who develop non-Hodgkin's lymphoma (NHL) have abnormal antibody responses against the Epstein-Barr virus (EBV) prior to the diagnosis of malignancy. To see if this is also true of "spontaneous" cases in the general population, we undertook a collaborative serologic case-control study. From 4 serum banks containing specimens from over 240,000 persons, 104 subjects were identified for whom a blood specimen had been stored an average of 63 months before diagnosis of NHL, and 259 controls matched for age, sex, ethnic group and date of serum collection. The relative risks (RR) for subsequent development of NHL associated with elevated levels of IgG and IgM antibodies against viral capsid antigen were 2.5 (95% confidence interval = 1.1-5.7) and 3.2 (1.3-7.5), respectively; these associations increased with age at diagnosis. For the nuclear antigen, the distribution of titers for cases was more restricted than that of controls, with fewer cases having either elevated or low titers, RR = 0.5 (0.2-1.4) and 0.5 (0.2-1.2), respectively. Cases had significantly lower antibody titers against the cytomegalovirus, RR = 0.4 (0.2-0.9). These findings suggest that, at least for some patients, NHL is preceded by an enhanced level of endogenous immunosuppression with resultant EBV activation. This observation supports the role of EBV either directly in the development of NHL or as a primary marker of immune dysfunction.

Adult↗

Epstein-Barr virus antibody patterns preceding the diagnosis of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) patients have elevated IgG and IgA antibody titers against the Epstein-Barr viral capsid antigen (VCA) and the diffuse component of the early antigen complex (EA-D) at diagnosis. Several studies have implied that the presence of anti-VCA-IgA can be used as a screening marker for early NPC. To evaluate this further, we undertook a serologic case-control study based on four serum banks which together had specimens from over 240,000 persons. Seven cases of undifferentiated or poorly differentiated NPC were diagnosed in the period after serum collection ranging from 26 months to 154 months. Two controls per case matched on serum bank, age, sex, race, and date of serum collection were selected by a predetermined random process. For anti-VCA-IgG, the geometric mean titer for cases (88.3) was significantly higher than that for controls (75.5, P less than 0.05). The difference was greatest among the Asian patients. No significant differences were found for anti-VCA-IgA, anti-EA-D, and anti-EA-R or anti-EBNA. No time effects were evident when titers were plotted against time of blood collection preceding diagnosis. Our results do not suggest EBV activation in the period preceding NPC diagnosis, nor that detectable IgA antibody against VCA is a marker for early disease.

Adult↗

Splenic hamartoma and capillary hemangioma are distinct entities: immunohistochemical analysis of CD8 expression by endothelial cells.

The histologic and immunohistologic features of two morphologically similar splenic tumors, a capillary hemangioma and a splenic hamartoma, are reported. The hemangioma was composed predominantly of small vascular channels lined by endothelium expressing factor VIII-related antigen and lacking T-subset antigen (CD8). In contrast, the splenic hamartoma was predominantly a spindle cell lesion with numerous vascular channels coursing through the tumor; these contained splenic-type endothelium expressing both CD8 and factor VIII-related antigen. Our results justify the concept that the splenic hamartoma is a tumor of splenic origin or a true hamartoma and is distinct from the splenic capillary hemangioma.

Aged↗

Fungi in megakaryocytes. An unusual manifestation of fungal infection of the bone marrow.

When fungi infect the bone marrow, typically they are associated with granuloma formation and/or necrosis, and the fungi are found within histiocytes or admixed with necrotic debris. Recently two bone marrow biopsy specimens were encountered in which fungi were confined to the cytoplasm of megakaryocytes, a finding not previously reported in the literature. The first case was that of a 46-year-old man with pulmonary histoplasmosis and no known immunodeficiency. The second was that of a 38-year-old man with the acquired immune deficiency syndrome and cryptococcal meningitis. In the first case, many megakaryocytes contained fungal forms consistent with Histoplasma. In the second, one small cluster of megakaryocytes contained several budding yeast consistent with Cryptococcus. Neither marrow biopsy specimen had necrosis, granulomas, or histiocytic infiltration. In both cases, because of the unusual localization of the fungi, they were initially overlooked. The bone marrow may contain fungi even in the absence of abnormalities suggesting fungal infection on routinely stained sections. A silver stain or a periodic acid--Schiff stain should be performed on all marrow biopsy specimens in cases of known or suspected fungal infection outside the marrow. The phenomenon of megakaryocyte emperipolesis is well known, and this process may be responsible for the apparent ability of megakaryocytes to internalize fungi.

Acquired Immunodeficiency Syndrome↗