Southern blot analysis of cerebrospinal fluid lymphocytosis.
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Blotting, Southern↗
Biomedical subjects
D J Innes
Publications and source records attributed to D J Innes.
Immunophenotypic analysis of sinonasal non-Hodgkin's lymphomas.
A panel of paraffin effective antibodies recognizing B cells and T cells (LN-2, MB1, L26, MT1, UCHL1, kappa, lambda) was used to characterize the immunophenotypes of 26 sinonasal non-Hodgkin's lymphomas. Seventeen tumors were stage I, five were stage II, one was stage III, and three were stage IV. Nine lymphomas were classified morphologically as large cell, six were large cell immunoblastic, six were small cleaved cell, two were mixed small and large cell, two were small noncleaved cell, and one was lymphoblastic. None were follicular. Twenty-two lymphomas had a B cell immunophenotype, three were T cell neoplasms, and one was immunoreactive only for MT1. This predominance of sinonasal lymphomas with a B cell immunophenotype in patients residing in the United States contrasts with the almost exclusive occurrence of T cell sinonasal lymphomas in Chinese patients living in Hong Kong and Japanese patients residing in regions of Japan that are nonendemic for human T cell leukemia virus-1.
Adolescent↗
Platelet vacuoles in acute megakaryoblastic leukemia.
The case of a 53-year-old man with acute megakaryoblastic leukemia (M7) was studied. At time of diagnosis, the platelet count was 980 X 10(9)/L and abnormal platelet vacuoles were present. The vacuoles were periodic acid-Schiff (PAS) positive. Electron microscopic examination showed large aggregates of glycogen. Findings of qualitative platelet function studies were abnormal. The authors' study and review of the literature indicates that thrombocytosis with large platelet vacuoles accompanying a blast cell population suggests a diagnosis of M7 and indicates the need for appropriate confirmatory studies.
Blood Platelets↗
Sequential bcl-2 and c-myc oncogene rearrangements associated with the clinical transformation of non-Hodgkin's lymphoma.
We report a case of untreated non-Hodgkin's lymphoma with histologic progression over 1 yr from a low-grade, small cleaved follicular center cell lymphoma to a high-grade, small noncleaved follicular center cell lymphoma. Both lymphomas had identical immunoglobulin (Ig) heavy-chain joining gene (JH), kappa light-chain joining gene, and bcl-2 gene rearrangements, indicating the clonal identity of the two tumors. The Ig heavy chain locus on one chromosome 14 was involved in an initial t(14; 18) translocation as shown by comigrating JH and bcl-2 rearrangements. However, the oncogene c-myc was in the germline configuration in the initial lymphoma but had one allele rearranged near the 3' end of exon I in the high-grade tumor; DNA sequence analysis was consistent with a chromosomal breakpoint at that site. The presence of the c-myc rearrangement in the high-grade tumor suggest a role for c-myc in the clonal evolution of the low-grade tumor into a more aggressive lymphoma. The coexistence of both bcl-2 gene and c-myc oncogene rearrangements in the same tumor is unusual, with only a few cases reported. Furthermore, this case is unique in the direct demonstration of the histologic and clinical progression of a human lymphoma associated with the sequential rearrangement of the bcl-2 gene and the c-myc oncogene.
Base Sequence↗
Transient myeloproliferative disorder. In a neonate with Down syndrome. Immunophenotypic studies.
This report describes the results of bone marrow leukocyte immunophenotypic studies, DNA index measurement, and chromosome analysis in a newborn with Down syndrome and transient myeloproliferative disorder. The infant's initial leukocytosis with immature cells in the peripheral blood and thrombocytopenia resolved without treatment by 6 months of age, and he was well at 2 years of age. The lack of specific reactivity between the patient's morphologically immature cells and multiple monoclonal antibodies directed against lymphoid and myeloid leukemia cells may be characteristic of this disorder. Other cases should be examined for immunophenotype to correlate the results with chromosomal analysis and to provide a basis for comparison in those who subsequently develop true acute leukemia.
Bone Marrow↗
Clostridium difficile toxin A. Interactions with mucus and early sequential histopathologic effects in rabbit small intestine.
Clostridium difficile produces two toxins, A (enterotoxic) and B (cytopathic), that are implicated in the pathogenesis of pseudomembranous colitis. However, the relationship of the secretory effect and the early histopathologic events is still unclear. We examined the early histopathologic effect of purified C. difficile toxin A in rabbit ileal loops and correlated the mucosal damage with the secretory response. As early as 2 hours after inoculation, toxin A at 1.0 micrograms caused cytolysis of the basal portion of the apical epithelia cells. Electron microscopy showed the basal portions of the absorptive epithelial cells necrotic. No significant fluid accumulation occurred after 2 or 4 hours in ileal loops inoculated with either 0.1 or 1.0 micrograms toxin A. In contrast, with 3-10 micrograms toxin A there was significant hemorrhagic fluid accumulation after 2 hours that correlated with the severity of the histologic lesions. An early mucoid exudate was demonstrated not to be related to a mucus secretagogue effect of toxin A. Prior exposure of toxin A to rabbit intestinal mucus preparations did not alter its subsequent enterotoxic or cytopathic (Chinese hamster ovary cells) effects. These studies demonstrate that the early intestinal tissue damage by toxin A was dose and time dependent and involved disruption of the basal portions of the absorptive epithelial cells with marked separation of the cells along the mucosal surfaces that preceded the secretory response.
Animals↗
Normal biochemical and hematological values in New Zealand white rabbits.
Animal model systems are used extensively for experimental in vivo studies. When biochemical and hematological measurements are made, reference intervals for the animal species must be determined. Here, the subjects for our study were young adult male New Zealand White rabbits. Blood was sampled from 110 normal healthy rabbits. Biochemical and hematological blood variables were measured by methods available in our routine service laboratory, and we report the ranges.
Alkaline Phosphatase↗
Intranasal tolerance and histopathologic effects of a novel synthetic interferon, rIFN-alpha Con1.
In a double-blind trial 119 adults were randomly assigned to receive daily sprays of placebo (N = 30) or rIFN-alpha Con1 3 MU (N = 29), 9 MU (N = 30), or 30 MU (N = 30) per day for 25 consecutive days. Fifty-nine subjects were removed from treatment because of abnormal nasal exams (N = 56) or irritative symptoms (N = 3). The fraction of drop-outs in the placebo group (30%) was significantly different (P less than 0.05) from that in the 3 MU (55%), 9 MU (57%), or 30 MU (67%) groups. Nasal mucosal biopsies collected 1-2 days after completing spray use detected moderate or marked lymphocytic infiltration in 10% of placebo (N = 10), 90% of 3 MU (N = 9), 85% of 9 MU (N = 13), and 70% of 30 MU (N = 10) subjects (P less than 0.05, placebo vs each rIFN-alpha Con1 group). All 3 dose levels of rIFN-alpha Con1 were associated with significant clinical and histopathologic signs of nasal irritation. The findings suggest that intranasal rIFN-alpha Con1 does not have a more favorable therapeutic index than rIFN-alpha 2 and that the risk of nasal irritation relates more closely to the anti-viral activity than the protein content of the rIFN-alpha administered.
Adult↗
Primary gastric lymphoma. Problems in staging and management.
A retrospective review of 28 patients with primary gastric lymphoma was performed to determine the optimal treatment modality. The presenting signs and symptoms resembled peptic ulcer disease or gastric carcinomas. The majority of the lymphomas were of the diffuse histiocytic subtype. There was a 75 percent resectability rate in those patients operated on. Palliative resection produced a 5 year duration of survival of 28 percent and curative resection, 43 percent. Eighteen patients underwent a subtotal gastrectomy, and a total of 10 patients presented with stage I disease. The longest median duration of survival at last follow-up was 32 months for patients with stage IB disease compared with a median duration of survival of 8 months for those with stage III disease. Adjuvant radiotherapy and chemotherapy may improve survival after a curative resection is performed if there is serosal penetration or nodal involvement.
Adult↗
Tolerance and efficacy of intranasal administration of recombinant beta serine interferon in healthy adults.
We performed two studies to determine the dose-related tolerance and the efficacy of recombinant beta serine interferon (rIFN-beta ser) in experimental rhinovirus infection. In the tolerance study, 120 healthy adults received intranasal sprays of rIFN-beta ser or placebo daily for 25 d. No differences in nasal symptoms were found. Rhinoscopy detected more mucosal bleeding sites in high-dose (38%) versus low-dose (12.5%) or placebo (12.5%) recipients. There were more subepithelial lymphocytes in nasal biopsy specimens in the high-dose (54%) than the low-dose (17%) or placebo (17%) groups. In the efficacy study, 34 volunteers received daily nasal drops of IFN, beginning 36 h before challenge and for three days afterwards. The numbers of infections and days of shedding of virus were not reduced, but colds occurred less often in the high-dose (25%) than in the low-dose (55%) or placebo (64%) recipients. Nasal mucus weights were lower in the high-dose (mean +/- SD g per five days; 5 +/- 4) than placebo (31 +/- 37) recipients. Thus, rIFN-beta ser may have a more favorable therapeutic ratio than do previously tested alpha interferons.
Administration, Intranasal↗
Nodular sclerosing Hodgkin's disease with giant Reed-Sternberg cells.
A 70-year-old woman with multiple symptoms and extensive lymphadenopathy had a lymph node biopsy specimen that contained highly pleomorphic, giant Reed-Sternberg cells that resembled cells from other malignant giant cell neoplasms. The cells were strongly positive for Leu-M1, alpha 1-antitrypsin, S-100 protein, kappa light chain, and lambda light chain. With five courses of chemotherapy for pathologic stage IV-B Hodgkin's disease, the patient achieved a complete remission, and remains free of disease 85 months after diagnosis.
Aged↗
Effects of Clostridium difficile toxins A and B in rabbit small and large intestine in vivo and on cultured cells in vitro.
Clostridium difficile is recognized as the major cause of antibiotic-associated colitis. C. difficile produces two toxins, A (enterotoxin) and B (cytotoxin), that are implicated in the pathogenesis of the colitis. We examined the dose responses, time course, and synergism of these two toxins in ligated rabbit intestinal loops and in tissue culture. In rabbit small intestinal loops, toxin A caused histologically demonstrable intestinal tissue damage as early as 2 h. The secretory response greater than or equal to 8 h was similar to that of a cholera toxin control. The effect of toxin A on tissue damage or secretion was seen even if toxin was removed after 5 min. Purified toxin A caused significant net accumulation of sodium, chloride, potassium, and total protein and slightly increased osmolality of the fluid content at 6 h; these effects were similar to those caused by crude C. difficile culture filtrates containing toxins A and B. Crude C. difficile toxin caused fluid accumulation with a delayed time course in the rabbit large intestine, and in contrast to its effect in small intestine, crude toxin caused net accumulation of bicarbonate and increased pH. In tissue culture, toxin A caused a rounding up of CHO and T-84 colonic carcinoma cells. A monoclonal antibody (PCG-4) that has no effect on tissue culture cytotoxicity with toxins A and B completely inhibited the secretory and tissue-damaging effects in the intestine. Toxins A and B were synergistic in the gut only at high doses of toxin B (greater than or equal to 10 micrograms/ml), and they were additive in tissue culture. The cytopathic effect in tissue culture was not consistently associated with trypan blue uptake. The cytopathic effect of toxin A in tissue culture did not appear to involve inhibitable Ca2+-dependent or prostaglandin synthesis pathways or intact microfilament or microtubule function for its activity and was not inhibited by reducing or lysosomotropic agents. Our results suggest that toxins A and B have independent and distinct effects in vivo and in vitro.
Animals↗
Lymphocyte subsets in normal airway mucosa of the human nose.
The distribution and number of lymphocytes, monocytes/macrophages, and cells expressing HLA-DR antigen were studied in frozen biopsy sections of nasal mucosa from 40 healthy adults, using monoclonal antibody avidin-biotin immunoperoxidase techniques. The lymphocyte to monocyte/macrophage ratio was estimated to be 10:1; the T cell to B cell ratio was 3:1; and the T helper/inducer cell to T suppressor/cytotoxic cell ratio averaged 2.5:1. Regional differences were observed with a relatively increased number of T suppressor/cytotoxic cells around submucosal glands, and a relatively large number of B cells in lymphocyte aggregates in the lamina propria. The HLA-DR antigen was expressed in epithelial cells, suggesting involvement of surface epithelium of human airway in local immune responses.
Adult↗
Lymphocyte subpopulations of plateletapheresis products collected with the Fenwal CS-3000 Cell Separator.
To determine whether any lymphocyte subset is preferentially harvested and transfused as a consequence of plateletapheresis with the Fenwal CS-3000 Blood Cell Separator, the proportions of lymphocyte subpopulations in platelet concentrates were compared to their proportions in the donors' peripheral venous blood immediately prior to platelet collection. There was no difference in the proportion of B cells (surface immunoglobulin positive), T cells (OKT3 positive), helper/inducer T cells (OKT4 positive), suppressor/cytotoxic T cells (OKT8 positive), and natural killer cells (Leu 7 positive) in the donors' peripheral venous blood and the plateletapheresis product. Thus, although previous studies have demonstrated the ability to separate lymphocyte subpopulations by density centrifugation and velocity sedimentation, plateletapheresis with the CS-3000 harvests the lymphocyte subpopulations studied in the same proportions in which they circulate in donors' peripheral venous blood.
Blood Component Removal↗
Tolerance and nasal histopathologic effects of long-term, low-dose intranasal recombinant interferon alpha-2A (Roferon-A).
The dose-related tolerance and histopathologic effects of intranasal recombinant interferon alpha-2a (rIFN-alpha 2a) were determined in a blind study in which healthy subjects were randomized to receive sprays of interferon (IFN) (3 or 6 MU/day) or placebo for 28 days. Adverse nasal symptoms (bleeding, obstruction, irritation) tended to occur more often in the IFN 6 MU/day group. Blind analysis of biopsy samples collected before and after IFN treatment revealed that both IFN groups had significant histologic changes, most commonly an increased degree of lymphocytic infiltration in the subepithelium and underlying glandular zones. Changes developed in 61% of 18 recipients of IFN 6 MU/day, 37% of 19 recipients of IFN 3 MU/day, and 6% of 18 placebo recipients. Serum antibodies to rIFN-alpha 2a detectable by EIA were found in 4 recipients of IFN 3 MU/day and 2 recipients of IFN 6 MU/day, one-third of whom were positive by neutralization bioassay. The findings would predict that these rIFN-alpha 2a dosages would be associated with an excess of adverse side effects during long-term use in healthy adults.
Administration, Intranasal↗
T-cells and macrophages in rapidly progressive glomerulonephritis: clinicopathologic correlations.
We phenotyped with monoclonal antibodies (MAb) the cellular infiltrates in kidneys of patients with rapidly progressive glomerulonephritis (RPGN) responsive (R) or nonresponsive (NR) to pulse methylprednisolone therapy (PM)-eight anti-GBM, six no immune deposits, three immune complex, two vasculitis, and one proliferative GN. There were glomerular, periglomerular, crescentic, and interstitial T and T-cell subsets. Few interstitial and no glomerular B and NK cells were observed. TH cells were much more common than TS. Phenotypes were quantitatively evaluated in 221 nephritic and 32 control glomeruli. T and/or TH cells were positively correlated with M phi, r = 0.30 to 0.74, P less than 0.05 to 0.0005. Although differences in phenotypes were observed, these differences were insufficient to distinguish between subtypes. Analysis of R and NR revealed no relationship to percent crescents, entry serum creatinine, oliguria, or need for dialysis. NR was related to presence of anti-GBM disease, P = 0.001, as was ability to stop dialysis, 0 of 7 GBM versus 9 of 10 other, P less than 0.001. Mild infiltrates of lymphocytes and M phi correlated with R, P less than or equal to 0.02. R had fewer numbers of TH and M phi in glomeruli, P = 0.0001, in crescents, P less than 0.02, and total TH and M phi compared to NR, P less than 0.001. Crescentic and total TH/S ratios were lower in NR than R, P less than 0.05. These findings demonstrate that components of the cell-mediated immune (CMI) system are present by MAb analysis, that subtypes cannot be differentiated by CMI constitution, and R to PM is related to intensity and composition of CMI involvement. Independence of the CMI system relative to anti-GBM disease remains to be clarified.
Antibodies, Monoclonal↗
Nonspecific esterase staining patterns in acute monocytic leukemia.
Staining patterns for nonspecific esterase (NSE) were analyzed retrospectively in 14 cases of acute monocytic leukemia (M5) using alpha-naphthyl acetate as substrate. An attempt was made to correlate variability in NSE activity with clinical findings. Two staining patterns were distinguished: (1) diffuse fine granular cytoplasmic staining, and (2) dense focal staining superimposed on a weak positive cytoplasmic background. The 14 cases were divided into two groups according to their different staining qualities: Group 1 (6) diffuse and Group 2 (8) focal. All six cases of Group 1 were typical hypercellular acute leukemias. Group 2 contained four cases of hypercellular acute leukemia and four cases of hypocellular acute leukemia. All the cases of hypocellular leukemia showed the pattern of focal NSE activity. No difference in the clinical presentation or course of the disease between Groups 1 and 2 was found.
Adolescent↗
Promyelocyte morphology. Differentiation of acute promyelocytic leukemia from benign myeloid proliferations.
Bone marrow aspirates from patients with acute agranulocytosis or a marked left shift in myeloid maturation can mimic acute leukemia, particularly acute hypergranular promyelocytic leukemia. Bone marrow aspirates from 16 cases of apparent acute promyelocytic leukemia, 4 cases of acute agranulocytosis, and 1 case of a marked myeloid left shift were studied for the presence or absence of differentiating features. Normal or reactive promyelocytes were characterized by prominent paranuclear clear Golgi zones, whereas promyelocytes from true leukemic cases all had heavy azurophilic granules dispersed diffusely throughout the cytoplasm. Prominent Golgi zones in promyelocytes were associated only with benign myeloid conditions and were not observed in acute promyelocytic leukemia. The presence of prominent clear Golgi zones in promyelocytes is an important feature assisting in the distinction between leukemic and benign promyelocytes.
Adult↗