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Biomedical subjects

D L Longo

Publications and source records attributed to D L Longo.

At least 433 records · Page 24Linked to original sources

Lymph node pathology of HTLV and HTLV-associated neoplasms.

Human T-cell leukemia/lymphoma virus I can transform mature T-lymphocytes in vitro and is associated with the human T-cell cancer, adult T-cell leukemia/lymphoma. Adult T-cell leukemia/lymphoma is a distinct clinicopathological entity associated with leukemia, lymphadenopathy, hepatosplenomegaly, skin lesions, hypercalcemia, and lytic bone lesions. Although morphologically diverse it pursues an aggressive clinical course. Human T-cell leukemia/lymphoma virus III is associated with acquired immunodeficiency syndrome, which in its early stages shows follicular lymphoid hyperplasia; however, lymphoid atrophy is progressive and ultimately results in virtually total lymphoid depletion of lymph nodes. Patients with human T-cell leukemia/lymphoma virus III infections appear to have an increased risk of high-grade B-cell lymphomas and perhaps Hodgkin's disease.

Acquired Immunodeficiency Syndrome↗

In vivo treatment of neonatal mice with anti-I-A antibodies interferes with the development of the class I, class II, and Mls-reactive proliferating T cell subset.

In this study we investigated the effect of monoclonal anti-I-A Ab treatment of neonatal mice on the development of alloreactive class I-specific, class II-specific, and Mls-specific T cell proliferative responses. Responses to both class I and class II alloantigens, as well as to Mls antigens, were nearly abrogated at the end of the 2- to 3-wk in vivo treatment period in both the thymus and the spleen. Development of suppressor cells could be excluded as the cause of the observed defect. Diminished responsiveness could not be restored by the addition of IL 2-containing supernatant, suggesting that the reduced T cell proliferative response in anti-I-A-treated mice is due to defective or absent MHC-specific T cell precursors. Furthermore, generation of alloreactive class I-specific proliferative responses was dependent on self-class II recognition, thus providing an explanation for the absence of class I-specific proliferating T cells. Finally, a non-Ia-restricted T cell response, i.e., Con A-induced proliferation, was not affected by anti-I-A Ab treatment. It was previously reported that neonatal anti-Ia Ab treatment results in reduced Ia-antigen expression in the thymus, and that the development of the class I-specific CTL precursors proceeds undisturbed in these mice. The present results extend these findings and suggest that in vivo development of class II-restricted T cells is dependent on interaction with Ia-encoded products on cells either in the thymus or at other sites where T cells undergo development. Moreover, these results demonstrate that in vivo development of the alloreactive class II-specific T cell repertoire is dependent on development of self-class II recognition.

Animals↗

Production and characterization of a monoclonal antibody that binds Reed-Sternberg cells.

A murine monoclonal antibody, termed HeFi-1, was produced after immunization with the L428 Hodgkin's disease tissue culture cell line. HeFi-1 selectively stained only the Reed-Sternberg or Hodgkin's cells in 18 of 18 cases of Hodgkin's disease, including the nodular sclerosis, mixed cellularity, and lymphocyte-depleted histologic subtypes. HeFi-1 did not stain any cells in normal lung, brain, salivary gland, thyroid, gall bladder, pancreas, liver, testis, breast, endometrium, or kidney. Rare large cells at the edge of the lymphoid follicles were stained in normal tonsil, colon, and hyperplastic thymus. There was no staining of any cells in 14 cases of B cell non-Hodgkin's lymphoma; however, the malignant cells in three of 11 cases of non-Hodgkin's lymphoma which appeared to express T cell markers were also stained with HeFi-1. Tissue culture cell lines including the T cell acute lymphocytic leukemia lines MOLT4 and CEM, the histiocytic cell line U-937, and the amniotic cell line WISH were not stained. Seven Epstein Barr virus (EBV)-positive lymphoblastoid cell lines were stained with HeFi-1, but there was no staining of three EBV+ African Burkitt's lymphoma cell lines or three EBV- American Burkitt's cell lines. HeFi-1 did not block the ability of the L428 cells to stimulate a mixed lymphocyte reaction or function as accessory cells for mitogen-induced human T cell proliferative responses. Modulation of the HeFi-1 cell surface antigen on the L428 cells was not observed. HeFi-1 specifically immunoprecipitated a cell surface protein of approximately 120,000 daltons from both the L428 and EBV+ lymphoblastoid cell lines. HeFi-1 monoclonal antibody should prove useful not only in the diagnosis, staging, and potential therapy of Hodgkin's disease, but also for determining the cell of origin of the Reed-Sternberg cell.

Animals↗

Deep venous thrombosis during therapy for Hodgkin's disease.

Upon reviewing the case records of 177 patients with Hodgkin's disease, we identified ten patients (6%) with deep vein thromboses confirmed by diagnostic tests. Most of the patients initially presented with advanced Hodgkin's disease as defined by stage and constitutional symptoms. Thrombotic episodes usually occurred between cycles of chemotherapy in the absence of clinically detectable tumor. Infusion of chemotherapeutic vesicants may have contributed to the high proportion of upper extremity deep venous thrombosis in this series. Thrombotic episodes did not necessarily imply recurrent disease. Three patients developed thromboses after completion of therapy and remained free of Hodgkin's disease or other malignancies at 85+, 18+, and 17+ months of follow-up.

Adolescent↗

Treatment of advanced non-Hodgkin's lymphoma with recombinant leukocyte A interferon.

We report the results of a trial of recombinant leukocyte A interferon in previously treated patients with non-Hodgkin's lymphoma who were no longer responsive to chemotherapy. Patients received recombinant leukocyte A interferon (50 X 10(6) U per square meter of body-surface area) by intramuscular injection three times weekly for three months or longer. Forty-five patients were enrolled in the study, and 37 were evaluated for a response. Thirteen of 24 (54 per cent) evaluable patients with low-histologic-grade non-Hodgkin's lymphoma had objective responses (nine partial responses and four histologically confirmed complete responses). Two of six (33 per cent) with intermediate-grade lymphoma responded (one partially and one completely), and one of seven (14 per cent) with high-grade lymphoma had a partial response. The median duration of responses was eight months. Four of the five complete responders have continued to receive maintenance interferon and have been in complete remission for 3, 7, 9, and 12 months, respectively; one had a recurrence at a site of previous disease seven months after interferon had been stopped. Side effects were noted in most patients. All 16 responders had been heavily pretreated with combination chemotherapy, including doxorubicin in 8 of the 16. These results suggest that recombinant leukocyte A interferon may be an effective new therapy for some patients with low- and intermediate-grade non-Hodgkin's lymphoma.

Adult↗

Self-recognition specificity expressed by T cells from nude mice. Absence of detectable Ia-restricted T cells in nude mice that do exhibit self-K/D-restricted T cell responses.

The presence in athymic nude mice of precursor T cells with self-recognition specificity for either H-2 K/D or H-2 I region determinants was investigated. Chimeras were constructed of lethally irradiated parental mice receiving a mixture of F1 nude mouse (6-8 wk old) spleen and bone marrow cells. The donor inoculum was deliberately not subjected to any T cell depletion procedure, so that any potential major histocompatibility complex-committed precursor T cells were allowed to differentiate and expand in the normal parental recipients. 3 mo after reconstitution, the chimeras were immunized with several protein antigens in complete Freund's adjuvant in the footpads and their purified draining lymph node T cells tested 10 d later for ability to recognize antigen on antigen-presenting cells of either parental haplotype. Also, their spleen and lymph node cells were tested for ability to generate a cytotoxic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified stimulator cells of either parental haplotype. It was demonstrated that T cell proliferative responses of these F1(nude)----parent chimeras were restricted solely to recognizing parental host I region determinants as self and expressed the Ir gene phenotype of the host. In contrast, CTL responses could be generated (in the presence of interleukin 2) to TNP-modified stimulator cells of either parental haplotype. Thus these results indicate that nude mice which do have CTL with self-specificity for K/D region determinants lack proliferating T cells with self-specificity for I region determinants. These results provide evidence for the concepts that development of the I region-restricted T cell repertoire is strictly an intrathymically determined event and that young nude mice lack the unique thymic elements responsible for education of I region-restricted T cells.

Animals↗

Evaluation of abdominal pain in the AIDS patient.

Acquired immune deficiency syndrome (AIDS) is a recently recognized entity characterized by a deficiency in cell mediated immune response. The syndrome is manifested by the development of otherwise rare malignant neoplasms and severe life-threatening opportunistic infections. Case histories of five AIDS patients evaluated for abdominal pain are presented to demonstrate the unusual spectrum of intra-abdominal pathology that may be encountered in the AIDS patient. As the number of patients with AIDS continues to escalate, surgical evaluation and intervention will be required more frequently. An understanding of this syndrome and its complications is mandatory for the surgeon to adequately evaluate AIDS patients with abdominal pain.

Abdomen↗

Kaposi's sarcoma of the head and neck in the acquired immune deficiency syndrome.

Since 1981 a new syndrome of acquired immune deficiency (AIDS) has been recognized. Male homosexuals, male and female intravenous drug abusers, and recipients of blood products (i.e., hemophiliacs) appear to be the populations at risk. The syndrome has been manifested by community-acquired opportunistic infections and/or Kaposi's sarcoma (KS). Otolaryngologic manifestations of AIDS are not infrequent. Thirteen AIDS patients at the National Institutes of Health with KS of the head and neck region are presented. All 13 patients were homosexual or bisexual males. Nine initially presented with KS, five with KS of the head or neck. As a group the patients demonstrated lesions involving the oropharyngeal, tracheobronchial, and gastrointestinal regions. Their clinical course and complications are presented in detail. The mortality rate in this subgroup of AIDS patients is extraordinarily high (62%), with an average longevity of 11 months following initial diagnosis.

Acquired Immunodeficiency Syndrome↗

Pharyngeal obstruction by Kaposi's sarcoma in a homosexual male with acquired immune deficiency syndrome.

A homosexual man with AIDS developed multifocal KS with involvement of the palate, larynx, trachea, and esophagus. Symptoms included dysphagia and gagging with resultant inanition. Short-course local radiation therapy effectively resolved the mucosal KS lesions in the treated areas. Other otolaryngologic manifestations included herpes stomatitis and oral candidiasis.

Acquired Immunodeficiency Syndrome↗

NIH conference. Acquired immunodeficiency syndrome: epidemiologic, clinical, immunologic, and therapeutic considerations.

The acquired immunodeficiency syndrome is a new disease whose cause is unknown but is almost surely due to a transmissible agent, most likely a virus. The disease is clearly spread by sexual contact, particularly homosexual activity. Blood-borne transmission constitutes the other major recognized form of spread of the disease, although it is highly likely that the disease is not readily spread through casual, nonsexual, non-blood-borne routes. Although the disease is still highly concentrated in the United States, it is now seen in several countries throughout the world. The common denominator of the disease is a profound suppression of cell-mediated immunity, specifically a quantitative and qualitative defect in the T4 inducer or helper subset of T lymphocytes. Hyperactivity of B lymphocytes is also characteristic. The clinical manifestations are those of severe and life-threatening opportunistic infections and unusual neoplasms, particularly Kaposi's sarcoma. The mortality may well approach 100%, making this one of the most extraordinary transmissible diseases in history.

Acquired Immunodeficiency Syndrome↗

Prolonged initial remission in patients with nodular mixed lymphoma.

Seventy-nine patients with nodular mixed lymphoma were treated at the National Cancer Institute between 1966 and 1978. Fifteen patients had stage I or II disease, and 64, stage III or IV disease. The overall complete response rate for the patients that received various primary treatment regimens was 76%, with 52% of complete responders remaining in their first remission at a median follow-up of 7 years. Median survival of complete responders is projected to be more than 13 years. Median survival of patients who do not achieve complete remission is less than 2 years. Patients with B symptoms, bone marrow involvement, or a lactate dehydrogenase level greater than 250 U/mL had significantly shorter survivals than did patients without these features. Patients with advanced-stage (III and IV) nodular mixed lymphoma had a 72% complete response rate, with the average remission lasting more than 6 years. Although relapses have been seen up to 8 years after diagnosis in patients with nodular mixed lymphoma given C-MOPP chemotherapy (cyclophosphamide, vincristine, procarbazine, prednisone), prolonged initial remissions can be achieved with this therapy.

Adult↗

Pneumocystis carinii pneumonia: a comparison between patients with the acquired immunodeficiency syndrome and patients with other immunodeficiencies.

Clinical features of 49 episodes of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome were compared with those of 39 episodes in patients with other immunosuppressive diseases. At presentation patients with the syndrome were found to have a longer median duration of symptoms (28 days versus 5 days, p = 0.0001), lower mean respiratory rate (23.4 versus 30, p = 0.005), and higher median room air arterial oxygen tension (69 mm Hg versus 52 mm Hg, p = 0.0002). The survival rate from 1979 to 1983 was similar for the two groups (57% and 50% respectively). Patients with the syndrome had a higher incidence of adverse reactions to trimethoprim-sulfamethoxazole (22 of 34 versus 2 of 17, p = 0.0007). Survivors with the syndrome at initial presentation had a significantly lower respiratory rate, and higher room air arterial oxygen tension, lymphocyte count, and serum albumin level compared to nonsurvivors. Pneumocystis carinii pneumonia presents as a more insidious disease process in patients with the syndrome, and drug therapy in these patients is complicated by frequent adverse reactions.

Acquired Immunodeficiency Syndrome↗