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T H The

Publications and source records attributed to T H The.

At least 145 records · Page 8Linked to original sources
PubMed1989

Kinetics of cytomegalovirus IgG antibody following infusion of a hyperimmune globulin preparation in allogeneic marrow transplant recipients.

We investigated prospectively cytomegalovirus (CMV) IgG antibody kinetics following infusion of a CMV hyperimmune globulin preparation in 19 consecutive patients undergoing allogeneic bone marrow transplantation (BMT). CMV IgG against late antigen was measured by enzyme-linked immunosorbent assay. On a prophylactic hyperimmune globulin regimen (100 mg/kg body weight every 20 days), the mean half-life (t1/2) +/- SD of CMV IgG in seronegative patients with seronegative marrow donors was 19.7 +/- 7.9 days after the first infusion on day -7 before BMT, 24.9 +/- 12.5 days after the second infusion on day +13 after BMT, and 19.4 +/- 6.9 days after the third infusion on day +33. The t1/2 in individual patients showed a wide variation ranging from 10.9 to 47.6 days. A therapeutic high-dose hyperimmune globulin regimen (200-400 mg/kg body weight at 4-day intervals) given to five patients resulted in high serum levels of CMV IgG, which were maintained throughout therapy, even in two patients with severe intestinal graft-versus-host disease. The variation of CMV IgG kinetics between individual BMT recipients may contribute to the lack of protection from active CMV infection observed in some patients.

Adolescent↗
PubMed1988

Rapid immunodiagnosis of active cytomegalovirus infection by monoclonal antibody staining of blood leucocytes.

The appearance of cytomegalovirus (CMV) antigen positive blood leucocytes (CMV antigenaemia) was investigated in 52 renal transplant recipients during the first three months after transplantation. Using a mixture of three monoclonal antibodies, CMV (immediate early) antigens were detected in cytocentrifuged blood leucocytes within 3-5 h after sampling. The results were related to virus isolation from buffy coats (CMV viraemia), serology with a sensitive enzyme-linked immunosorbent assay (ELISA), and clinical symptoms of CMV disease. The antigen test was positive in all 14 patients with CMV viraemia, in 25 out of 27 of patients with serological evidence of primary or secondary CMV infection, and in 2 out of 25 patients without active infection. In patients with a clinical CMV syndrome the presence of CMV antigen (CMV-Ag) positive blood cells correspond with the period of signs and symptoms. CMV antigens were not detected in 23 out of 25 patients without active infection, nor in healthy controls and patients with other herpesvirus infections. CMV-Ag positive blood cells appeared, on average, nine days before serological signs of active infection. This method provides a rapid and sensitive approach to CMV detection, enabling early clinical diagnosis and subsequent tapering of immunosuppression or commencement of antiviral therapy.

Adult↗
PubMed1988

Comparison between viremia and antigenemia for detection of cytomegalovirus in blood.

In a prospective study, 139 serial blood samples from 15 transplant recipients were assessed for the presence of cytomegalovirus (CMV) by virus isolation (CMV viremia) and by direct staining of CMV antigens (CMV Ag) in blood leukocytes (CMV antigenemia). CMV was isolated from 23 samples, whereas CMV Ag was detected in 44 specimens. All positive samples were from a total of nine patients who were diagnosed as having active CMV infections. In seven patients, active CMV infections were diagnosed by virus isolation from blood and urine and by a significant rise of CMV-specific antibodies. In these patients, 21 of the 23 blood samples which were positive for CMV by cell culture were also positive by direct CMV Ag detection. Moreover, CMV Ag were detected in 23 of the 116 culture-negative samples. Twenty of these samples were from the acute phase of infection in the same seven patients. The remaining three CMV Ag-positive specimens were from the other two patients, from whom CMV was not isolated but who had serological evidence of concomitant active CMV infections. These results suggest that direct detection of CMV Ag in peripheral blood leukocytes is as specific as and more sensitive than current isolation techniques. Furthermore, by its sensitivity and inherent rapidity the antigen detection test proved to be the earliest diagnostic marker of active CMV infection in eight of the nine patients. Finally, it was shown that monoclonal antibodies to CMV immediate early antigens are a prerequisite for demonstration of CMV antigenemia.

Antigens, Viral↗
PubMed1988

Detection of small cell lung cancer metastases in bone marrow aspirates using monoclonal antibody directed against neuroendocrine differentiation antigen.

To detect metastases in the bone marrow of patients with small cell lung cancer, immunofluorescence with a monoclonal antibody detecting a membrane antigen (MOC-1) associated with small cell lung cancer was performed on 53 bone marrow aspirates from 30 patients. In 19 (63%) patients MOC-1 reactive cells were detected. Simultaneous histopathological examination of the bone marrow biopsy specimens detected tumour cells in only six (20%). The method is more sensitive than conventional histochemical staining of bone marrow aspirate and may eventually be able to show additional subgroups, such as patients with limited disease who might benefit from adjuvant radiotherapy or surgery.

Antibodies, Monoclonal↗
PubMed1988

The cellular immune response to cell-associated and cell-free cytomegalovirus (CMV) antigens after primary CMV-infection in non-immunocompromised hosts: development and maintenance of CMV-latency and its influence on immunocompetence.

Development and maintenance of cellular immunity to cell-associated CMV-antigens (CMVFF) was investigated in non-immunocompromised hosts during the first year (group I, n = 11) and 1 to 5 years (group II, n = 9) after a symptomatic primary CMV infection, as well as in healthy CMV-seropositive controls without a history of CMV disease (group III, n = 28). During the acute phase (0-2 months) of a primary CMV-infection CMVFF-induced lymphocyte proliferation was severely decreased compared to that in the post-illness phase (5-12 months), and to that in groups II and III. After the reconvalescent period (3-4 months) it gradually increased to levels seen in group III. In group II higher responses to CMVFF were found than in group III or during the post-illness phase of a primary infection. In general CMV-virion induced lymphocyte proliferation showed the same pattern of development as the CMVFF-induced lymphocyte response, but during the acute phase (0-2 months) a lack of correlation was observed between lymphocyte proliferation to CMVFF and CMV-virions. Lymphocyte proliferation to PHA, Con A, allogeneic lymphocytes and recall antigens were severely depressed in the acute phase of a primary CMV-infection and restored gradually to levels seen in groups II and III, with the exception of Con A-reactivity. The latter response remained depressed when compared to healthy seropositive controls, not only during the post-illness period, but also later on (group II).

Adult↗
PubMed1988

B-cell proliferation and differentiation in systemic lupus erythematosus and mixed connective tissue disease.

Systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) are characterized by B-cell hyperactivity as manifested by spontaneous in vitro production of immunoglobulins (Ig), but pokeweed mitogen (PWM)-induced Ig synthesis of peripheral blood (PB) mononuclear cells, a T-cell dependent process, is markedly decreased. We analyzed the defective capacity to produce Ig in vitro in 11 patients with SLE and 11 with MCTD. PWM-activated PB T-cells, both from SLE- and MCTD-patients, did not differ from control T-cells in their capacity to produce B-cell growth factors (BCGF) and B-cell differentiation factors (BCDF). However, B-cell proliferative responsiveness to control T-cell factors was decreased compared to control B-cells (p less than 0.01). In contrast to PB B-cells splenic B-cells from a patient with MCTD who underwent splenectomy were highly responsive to T-cell factors in a dose dependent way. It is concluded that the defective PWM-induced Ig production of PB lymphocytes in SLE/MCTD is due to decreased responsiveness of PB B cells to T-cell factors. However, analysis of splenic lymphocytes may be more representative for evaluation of the immunoregulatory disturbances in these disorders.

Adult↗
PubMed1987

Herpes-virus immunity and acute graft-versus-host disease.

The influence of pretransplant herpes-virus antibodies in 126 marrow-graft recipients and their HLA-identical (A, B, C, DR) sibling donors on the incidence of grades II-IV acute graft-versus-host disease (GVHD) was studied in relation to previously reported risk factors for GVHD. Logistic regression procedures were used to control for confounding factors. Increasing donor age (odds ratio 3.7 per decade; p = 0.02) and donor seronegativity for Epstein-Barr virus (EBV; odds ratio 10.1; p = 0.005) were associated with a high incidence of GVHD. Total rather than selective gastrointestinal decontamination (odds ratio 0.1; p = 0.004), donor seronegativity for herpes simplex virus (HSV; odds ratio 0.1; p = 0.003), and recipient EBV-seronegativity (odds ratio 0.05; p = 0.002) were associated with a low incidence of GVHD. Pretransplant EBV and HSV serology may thus contribute substantially to the estimation of the risk for GVHD.

Acute Disease↗
PubMed1987

Rapid detection of infectious cytomegalovirus in blood with the aid of monoclonal antibodies.

The recently developed early antigen immunofluorescence (IF) method for the detection of infectious cytomegalovirus (CMV) in clinical specimens has hardly been applied on blood samples. We compared the CMV early antigen detection technique with the conventional cell culture method in 415 different buffy coat samples from 85 different immunocompromised patients. Duplicate coverslips were stained with two different monoclonal antibodies 4-6 days after inoculation. The conventional cultures were examined for typical cytopathic effects (CPE) during 10 weeks. Forty samples from 19 patients were positive by the IF technique, most of them with both monoclonal antibodies. Only 22 of these samples were positive in the conventional cell culture assay, on average after 15.8 days. CMV viraemia was detected exclusively by the IF method in 18 samples, 7 of which were from five patients without any further evidence of an active CMV infection. CMV viraemia was detected exclusively by the CPE method in eight samples, on average after no less than 36.6 days. CMV viraemia was not found in blood samples from 10 patients with laboratory proven active CMV infections and 53 patients without any evidence of an active CMV infection. In our hands the early antigen method for the detection of infectious CMV in blood is nearly as specific (at least 98.1%) and clearly much faster and more sensitive than the conventional cell culture method. The early CMV antigen detection method is therefore a very useful tool for the rapid detection of infectious CMV in blood.

Antibodies, Monoclonal↗
PubMed1987

Expression of class II major histocompatibility complex antigens on alveolar epithelium in interstitial lung disease: relevance to pathogenesis of idiopathic pulmonary fibrosis.

To determine whether expression of class II major histocompatibility complex antigens on alveolar epithelium is relevant to the pathogenesis of idiopathic pulmonary fibrosis (IPF) lung biopsy specimens were investigated from nine patients with IPF with or without connective tissue disease, four patients with sarcoidosis, eight patients with lung disease of presumably infectious origin, and five controls. The alveolar epithelium stained strongly with anti-Ia (HLA-DR) or Leu 10 (HLA-DS) monoclonal antibodies, in eight of nine biopsy specimens from patients with IPF, in three of four biopsy specimens from patients with sarcoidosis, in all six biopsy specimens from patients with presumably viral, mycobacterial, or pneumocystic lung disease, but not in control lung tissue, nor in two biopsy specimens from patients with bacterial pneumonia. Mononuclear cell infiltrates consisted of T4 positive (helper/inducer) lymphocytes, predominantly present in a nodular arrangement in the interstitium, and T8 positive (cytotoxic/suppressor) cells, distributed equally in the interstitium and subepithelially or intraepithelially. T8 cells outnumbered T4 cells in six of nine biopsy specimens from patients with IPF, but in none of the biopsy specimens from patients with sarcoidosis or interstitial lung disease of infectious origin. Although the expression of class II antigens on the alveolar epithelium which is infiltrated by T8 cells in IPF is consistent with local presentation of autoantigens and an ensuing local immune response, class II expression is also present in interstitial lung disease of sarcoidosis and microbial infections: its role in the pathogenesis of IPF must therefore remain speculative.

Adolescent↗
PubMed1987

The influence of cytomegalovirus carrier status on lymphocyte subsets and natural immunity.

The influence of the cytomegalovirus (CMV) carrier status on peripheral lymphocyte subsets was studied in 70 healthy individuals. IgG-class antibodies against CMV late antigen were used as markers for the presence of CMV in those individuals. The 39 CMV-seropositive individuals had significantly higher numbers of CD3+ (P = 0.009), CD8+ (P = 0.005) and HNK1+ (P = 0.002) cells than the 31 CMV-seronegative individuals. Two-colour immunofluorescence studies revealed that the HNK1+ cells coexpressing CD4 or high density CD8 were particularly increased in the number under the influence of CMV, but not the HNK1+ cells coexpressing CD16. Since HNK1 and CD16 are markers associated with natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC), we investigated the influence of the CMV carrier status on those functions. The NK and ADCC functions of peripheral blood mononuclear cells (PBMC), HNK1+ and HNK1- cells were correlated with the percentages of CD16+ cells among those cells. Although CMV-seropositive individuals had significantly less CD16+ cells among their HNK1+ cells than CMV-seronegative individuals (mean and s.d.: 39 and 19%, versus 58 and 11%, P = 0.003), the NK and ADCC functions of the HNK1+ cells were similar in both groups. Also, the CMV carrier status did not influence significantly those functions of PBMC and HNK1- cells. We conclude that the CMV carrier status, i.e. CMV-seropositivity, is associated with a significant increase in the numbers of HNK1+ lymphocytes coexpressing T cell markers. That situation may reflect the continuing interaction between CMV and the immune system of its host.

Adult↗
PubMed1987

Intermediate filament expression in small cell lung cancer; poor correlation to in vitro data.

A panel of monoclonal antibodies, detecting different intermediate sized filament proteins, was prospectively applied on all specimens derived from S.C.L.C. patients attending our clinic in 1985. Reactivity with the antibodies was subsequently correlated to clinical data. The results indicate a heterogeneous pattern of reactivity of the assessed antibodies. However this heterogeneity is not a straightforward extension of the intermediate sized filament expression in SCLC cell lines.

Antibodies, Monoclonal↗
PubMed1987

Marrow donor immunity to herpes simplex virus: association with acute graft-versus-host disease.

The interactions between humoral and cellular immunity to herpes simplex virus (HSV) in bone marrow donors, the occurrence of active HSV infections, and the development of grades II-IV acute graft-versus-host disease (GVHD) in their HLA-A,B,C,DR-identical sibling recipients were studied. The absence of IgG-class HSV antibodies in the marrow donors was associated with a low incidence of GVHD: 38 of 53 recipients (72%) of marrow from HSV-seropositive donors developed GVHD versus only two of 15 recipients (13%) with HSV-seronegative donors (p = 0.0004). The cellular immunity to HSV was studied in vitro by evaluating the degree of lymphocyte proliferative responses to that virus and was also significantly associated with GVHD: 30 of 43 recipients (70%) of marrow from donors with a positive test developed GVHD versus 10 of 25 recipients (40%) of marrow from donors with a negative test (p = 0.03). The previously reported risk for GVHD attributed to donor CMV antibodies increased the risk of GVHD due to donor HSV antibodies. Of 31 recipients of marrow from donors who were both HSV- and CMV-seropositive, 27 (85%) developed GVHD versus 11 of 22 recipients (50%) of marrow from HSV-seropositive but CMV-seronegative donors (p = 0.008).

Adolescent↗
PubMed1987

Expression of class II MHC antigens on alveolar epithelium in fibrosing alveolitis.

Lung biopsy specimens from eight patients with fibrosing alveolitis with or without connective tissue disease were investigated for the presence of immune deposits and the expression of class II histocompatibility antigens on the alveolar epithelium. Immune deposits were not detected. The alveolar epithelium stained strongly with anti-Ia (HLA-DR) monoclonal antibodies in seven out of eight biopsy specimens from the patients, but not in control lung tissue. Sub- and intra-epithelially localized mononuclear cell infiltrates consisted predominantly of T8-positive (cytotoxic/suppressor) lymphocytes. The expression of class II antigens on the alveolar epithelium and its infiltration with T8 positive cells is consistent with local presentation of self-antigens and an ensuing local immune response.

Adult↗
PubMed1986

Diagnostic application of a monoclonal antibody against small cell lung cancer.

A monoclonal antibody (MOC-1) directed against an antigen present in small cell lung cancer (SCLC) was used for diagnostic purposes. After screening of biopsy specimens of lung tumors, MOC-1 was found to react with SCLC (n = 10) and adenocarcinoma of the lung (4 of 9 cases). Except for a few cells in a poorly differentiated tumor, the reaction with squamous cell cancer was negative (n = 6). Staining with MOC-1 by an immunoperoxidase technique on imprints of biopsy specimens procured by rigid bronchoscopy was found to be a reliable and rapid method for diagnosing SCLC (16 of 17 positive). All cytologically proven bone marrow and pleural metastases of SCLC were found by staining on a cytospin preparation with MOC-1. Moreover, in three cytologically negative cases, MOC-1-positive cells were detected.

Antibodies, Monoclonal↗