Improving the heavy-Higgs-boson two-charged-lepton-two-neutrino signal.
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Biomedical subjects
Publications and source records attributed to T Han.
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We describe a case of human T-lymphotropic virus type I (HTLV-I)-associated transient benign immature T-cell lymphocytosis in a black female patient, which over the course of several months underwent spontaneous complete remission. The patient presented with a white blood cell count of 20,000/microliter and a T4/T8 ratio of 1.7:1. The majority of cells appeared to be lymphoid in origin, and cell marker analyses established that the circulating lymphocytes were predominantly immature T-cells. HTLV-I was detected at this time by a p19 indirect immunofluorescent slide assay. Over a 1-month period of time the patient's clinical status evolved into a mature T-lymphocytosis with a T4/T8 ratio of 4.5:1. HTLV-I was detected by anti-p19 immunofluorescence by cell sorter analyses and by dot-bloc nucleic acid hybridization. Serological testing demonstrated that the patient had anti-HTLV-I antibodies and antimembrane antibodies specific for an HTLV-I producing cell line. In a competitive HTLV-I ELISA assay only HTLV-I proteins could effectively compete out the seroreactivity. The patient also had a high serum level of soluble interleukin-2 (IL-2) receptors, which is associated with HTLV-I infection. This is the first reported case of immature T-lymphocytosis in a patient infected with HTLV-I. The patient's HTLV-I markers disappeared with time, and her lymphocytosis subsequently spontaneously resolved. She remains disease free and virus negative after 2 years of follow-up study.
Solid and granular porous hydroxylapatite implants were compared in the surgical treatment of angular interproximal periodontal defects in 10 subjects. After completion of initial therapy, presurgical measurements of pocket depth, attachment level, gingival recession, gingival fluid and tooth mobility were recorded. Six months after the surgery the measurements were repeated. The use of both forms of porous hydroxylapatite resulted in reduction in pocket depth, and probeable attachment level gains as well as gingival recession and reduction of gingival fluid and tooth mobility. These changes were similar for both granular and solid forms of porous hydroxylapatite.
A routine method allows bone marrow biopsy specimens to be embedded in glycol methacrylate (GMA), a water miscible plastic, and to benefit from the advantages of good morphology with immunoperoxidase detection of a wide range of cellular antigens useful in diagnosing and classifying various haematopoietic disorders. Marrow cores were fixed in cold Bouin's solution, rinsed in cold phosphate buffer, dehydrated in cold methanol, infiltrated and embedded in cold GMA, then polymerised at 4 degrees C. Sections were cut at 2 micron thickness with a Tungsten carbide knife in a Jung's high performance microtome (Autocut). Antigenecity was preserved when drying slides at room temperature but pronase digestion was necessary to re-expose the antigens in bone marrow biopsy sections embedded in GMA. Histostik, a new adhesive, was used to coat the glass slides to prevent section loss during enzyme digestion and immunostaining procedures. This method of adapting plastic embedding to undecalcified marrow cores preserves marrow architecture and cellular details and it can serve as a useful adjunct to analyse the bone marrow from patients with myeloproliferative and lymphoproliferative disorders. This technique may also be applicable in non-haematological malignant conditions which affect the marrow.
We studied the B lymphocyte metaphases in 78 of 94 cases of CLL, 24 of our 28 hairy cell leukaemias, 4 CLL's which transformed into prolymphocytic leukaemia and 8 original prolymphocytic leukaemias. Twelve CLL's were carriers of trisomy 12, 13 of this trisomy 12 with other abnormalities and 15 had other abnormalities without trisomy 12. Trisomy 12 seemed to be more frequent in patients with CLL or prolymphocytic leukaemia with a monoclonal gammopathy. In contrast to our previous results, the isolated finding of a trisomy 12 had an influence on the median survival.
Iliac crest trephine biopsy specimens from 16 patients treated with recombinant alpha 2-interferon (alpha-IFN) for hairy cell leukemia (HCL) were examined for reticulin and collagen content. These data were compared with the hairy cell index (HCl), the proportion of hairy cells to the overall cellularity of the bone marrow. Specimens were studied immediately before alpha-IFN therapy, at 6-month intervals during, and in six patients 6 months after cessation of therapy. All patients presented with increased bone marrow fibrosis ranging from focally increased reticulin to a diffuse increase in both reticulin and collagen content. This fibrosis was observed to decrease during alpha-IFN therapy inasmuch as the hairy cell population was diminished in the bone marrow in 13 patients. Regression analysis of HCl v bone marrow fibrosis showed a positive correlation (r = .73, P less than .02). Six patients demonstrated a reduction in bone marrow reticulin and collagen to normal levels during alpha-IFN therapy. Two of six patients demonstrated increased bone marrow fibrosis and HCl 6 months after cessation of alpha-IFN therapy. Three of 16 patients exhibited no decrease in bone marrow reticulin content during therapy despite a decreased bone marrow hairy cell population.
Autopsy data on 1,206 children and adult patients with acute myelocytic leukemia (AML) (585), chronic granulocytic leukemia (CGL) (204), acute lymphocytic leukemia (ALL) (308), and chronic lymphocytic leukemia (CLL) (109) obtained from 1958 to 1982 were reviewed. This analysis has shown that, whereas the proportion of patients with residual AML at any anatomic site decreased significantly and uniformly over the entire study period, significant corresponding decreases in patients with CGL and ALL occurred only since 1976 and 1978, respectively. No significant corresponding decreases were noted in patients with CLL at any time. Significant decreases were also noted over time in the rates of extramedullary site involvement by AML, CGL, and ALL. Whereas the lymphoreticular organs, kidneys, adrenals, and pituitary were most often involved at autopsy by CLL, the testes, leptomeninges, dura mater, uterus, large bowel, and pancreas were most often involved by ALL. In general, patients with AML and CGL showed the lowest relative rates of involvement of the various organs by leukemia during the 24-year period. Whereas patients with AML and ALL showed significant decreases in the rates of involvement of nearly all anatomic sites during the most recent study periods, those with CGL and CLL showed corresponding decreases in only a few organ sites. The lower rates of organ involvement in patients with AML and ALL attest to the more aggressive eradication of leukemic cells by therapeutic regimens in these diseases over time. In particular, the significant decrease in the rate of meningeal involvement by ALL during the most recent period is probably attributable to central nervous system prophylaxis.
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Seventy three patients with disseminated diffuse non-Hodgkin's lymphomas were treated with combinations of cyclophosphamide, vincristine sulfate, prednisone, and doxorubicin with and without 2 weekly doses of oral methotrexate in "intermediate" doses, followed by calcium leucovorin rescue. The addition of methotrexate did not increase the complete remission rate, the remission duration, or the survival (P value = 1.0, 0.74, and 0.78, respectively) in patients who did not have previous chemotherapy treatment. In previously treated patients, the complete remission rate was somewhat higher and the remission duration and survival were longer among those patients treated with the methotrexate containing program; however these differences were not statistically significant (P values = 0.88, 0.81, and 0.46, respectively). There was substantial morbidity and mortality during treatment with both treatment arms, among patients aged more than 60 years.
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Eleven patients with Hodgkin's disease refractory to chemotherapy were treated with six cycles of intermediate-dose methotrexate with calcium leucovorin rescue, followed by cyclophosphamide, doxorubicin, vincristine, and prednisone (MTX-CHOP). Three other patients were treated with a similar program of treatment minus doxorubicin (MTX-COP). The overall response rate was 57%, with four (29%) patients achieving a complete response and four patients achieving a partial response. None of the three patients treated with MTX-COP had a complete remission (CR); thus the complete remission rate with MTX-CHOP was somewhat higher (36%). Only one of the CR's is in continuous complete remission and free of disease at 99+ months. One patient died of overwhelming sepsis and pancytopenia during treatment. Hematologic toxicity in the other patients was acceptable. The overall median survival was 18 months. The search for an effective treatment program for this group of patients remains a major challenge.
Cytogenetic analyses were performed on cells from 17 patients with hairy cell leukemia stimulated with polyclonal B-cell activators (in 155 different cultures). No mitosis was obtained in samples from four cases (23.5%). Of 14 bone marrows, four (28.6%) showed mitoses, two with clonal abnormalities. All four samples from the spleen had mitoses with four clonal changes; eight of 13 (37.5%) blood samples had mitoses with three clonal changes. Of the polyclonal B-cell activators (PBA), lipopolysaccharide and protein A seemed to be effective for the detection of clonal abnormalities in hairy cell leukemia. Among the clonal aberrations, chromosomes #3, #10, and #17 were affected in two cases each; frequent numerical changes were monosomies of #10 and #17 and structural changes were deletions at band 3p21 (two cases), 6q-, and der(9)t(9;?)(p22;?). The chromosomal bands involved in structural changes were close to accepted constitutive fragile sites.
The anti-granulocyte activity of serum from patients with B-cell chronic lymphocytic leukaemia (CLL) and other lymphoproliferative disorders was investigated. Granulocyte-binding IgG was measured in 34 patients with CLL, 13 patients with hairy cell leukaemia, one patient with prolymphocytic leukaemia, two patients with Sézary cell leukaemia, and seven patients with chronic T-cell lymphocytosis who had a predominance of circulating large granular lymphocytes. Anti-granulocyte activity was absent in CLL and its variants, but present in the majority of granulocytopenic patients with chronic T-cell lymphocytosis. In one of these patients, granulocytopenia was associated with complement-activating IgG granulocyte antibody. Thus, antibody-mediated granulocyte injury appears to be an unusual occurrence in chronic lymphocytic leukaemia, but is a frequent complication of chronic T-cell lymphocytosis.
Cytogenetic analyses by G-banding and/or Q-banding techniques of leukemic B cells were performed in 102 patients with chronic lymphocytic leukemia (CLL), including six with prolymphocytic leukemia (PLL), one with hairy cell leukemia (HCL), and one with Waldenstrom's macroglobulinemia (WM) from 1979 through 1983. Follow-up after cytogenetic study ranged from 24 to 70 months. Seventeen patients had stage 0, 10 had stage I, 31 had stage II, and 44 had stage III or IV. Adequate metaphases were obtained for karyotypic analysis in 86 (84%) of 102 patients. Of these 86 patients with adequate metaphases, 43 had normal karyotypes (50%) and 43 had abnormal karyotypes (50%), of which trisomy 12 was the most frequent. Ten patients had trisomy 12 as the sole abnormality, 14 had trisomy 12 in combination with other abnormalities, and the remaining 19 had other abnormalities without trisomy 12. Abnormal karyotypes were more frequently associated with patients with advanced stages than those with early stages of the disease. Response rate to chemotherapy was significantly higher in patients with normal karyotypes than in those with abnormal karyotypes. Of eight patients who subsequently developed Richter's syndrome, seven initially had complex karyotypic changes with or without trisomy 12. These observations suggest that the chances of development of Richter's syndrome in CLL patients with multiple chromosome changes may be much higher than in those with either simple trisomy 12 or a normal karyotype. Mean frequency of abnormal metaphases was significantly higher in patients with complex trisomy 12 in combination with other changes than in those with trisomy 12 as the sole abnormality.(ABSTRACT TRUNCATED AT 250 WORDS)
Prolymphocytic leukemia is characterized by a low response rate to agents that are effective in the treatment of chronic lymphocytic leukemia. A 75-year-old man with prolymphocytic leukemia was followed up over a period of 69 months. During that time, he was treated with high-dose chlorambucil plus prednisone; cyclophosphamide administered daily; combinations of vincristine sulfate, prednisone, and cyclophosphamide; irradiation to the spleen; and alpha-interferon without substantial antitumor effect. The patient had a brief response after splenectomy. When he received low-dose vincristine therapy daily with high-dose prednisone therapy given on alternate days, a fatal tumor lysis syndrome occurred. Although rare, this complication should be kept in mind, particularly in patients who had rapid reduction of tumor cells.
The chromosomal constitution of stimulated lymphocytes in 13 patients with B cell chronic lymphocytic leukemia (B-CLL) were sequentially examined using polyclonal B cell activators (PBA), i.e., Epstein-Barr virus (EBV), lipopolysaccharide W from E. coli (LPS), pokeweed mitogen (PWM), and protein A from Staphylococcus aureus (PA). Of the 11 patients (44 samplings) with abnormal clones, 2 patients had only trisomy 12, 6 patients had trisomy 12 plus other clonal abnormalities, such as +8, +9, +16, +18, 6q-, 15q+, and t(4;15), and the remaining 3 cases had various clonal abnormalities other than trisomy 12, such as trisomy 3, 8, 20, 21, and insertion of #7 and #12. These findings suggest that even though trisomy 12 may be a common abnormality in B-CLL, various other abnormal clones may also be present in vivo for relatively long periods of time. It appears that stimulated lymphocytes in patients with previous therapy tend to show chromosome abnormalities more frequently than those in untreated patients.