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M Robert-Guroff

Publications and source records attributed to M Robert-Guroff.

At least 109 records · Page 6Linked to original sources
PubMed1984

Transformation of different phenotypic types of human bone marrow T-lymphocytes by HTLV-1.

Fresh bone marrow mononuclear leukocytes were used as a target for infection by human T-cell leukemia-lymphoma virus subgroup 1 (HTLV-1) by co-cultivation with virus-positive cell lines. The lines were established from T-cell leukemia-lymphoma patients or HTLV-1-transformed human umbilical cord-blood T cells. Clumps of transformed cells became visible by 2-3 weeks after infection and developed at a high frequency (greater than 90%) in the bone marrow samples used. Stimulation of target cells with lymphocyte mitogens facilitated this process but was not absolutely required. Unlike fresh or cultured cells from HTLV-1-positive adult leukemia-lymphoma patients and HTLV-1-transformed cord-blood T cells, which usually have an OKT 4/leu 3a surface phenotype, the transformed bone marrow cells frequently fell into one of three categories based on their reactivity with cell-specific monoclonal antibodies. These included populations of cells that were predominantly; (1) OKT 4/leu 3a-positive, (2) OKT 8/leu 2a-positive, and (3) cells expressing neither phenotype. Fresh bone marrow provided a rapid and efficient system for the assessment of HTLV-1 infection. The type of bone marrow cells transformed in vitro suggests that HTLV-1 can infect several subsets of T lymphocytes, possibly including immature cells or that these cells can undergo phenotypic modulation.

Bone Marrow↗
PubMed1984

Prevalence of HTLV-specific antibodies in Surinam emigrants to The Netherlands.

Sera of 98 participants in a methadone maintenance programme, all recent Surinam emigrants to the Netherlands, were examined for antibodies to disrupted HTLV using the ELISA technique. Twelve per cent of the donors possessed HTLV-specific antibodies with a range of titre from 41 to 20,000. Sera of 26 control Dutch drug users lacked such antibodies with the exception of one female who subsequently was found to reside with a Surinam male. Intravenous drug use was not a factor in these studies. These data indicate that HTLV circulates within the Surinam community in the Netherlands. More broadly, these results show that the region of the Caribbean endemic for HTLV extends as far south as Surinam. Furthermore, an antibody prevalence of 12% for clinically healthy donors with non-malignant disease suggests that the Caribbean has an incidence of HTLV infection approaching, if not equal to, that of southwestern Japan.

Adult↗
PubMed1984

The pathologic spectrum of adult T-cell leukemia/lymphoma in the United States. Human T-cell leukemia/lymphoma virus-associated lymphoid malignancies.

The human T-cell leukemia/lymphoma virus (HTLV) is a novel Type-C retrovirus isolated from patients with post-thymic T-cell malignancies. Thirteen patients diagnosed in the United States were identified as having antibodies to HTLV and a typical clinicopathologic syndrome characteristic of adult T-cell leukemia/lymphoma as described in Japan. The most characteristic diagnostic feature in our series was the presence of highly pleomorphic and lobated lymphoid cells in the peripheral blood. Also notable was acid phosphatase activity which was partially tartrate-resistant in the neoplastic cells. The pathologic spectrum of the associated lymphomas was broad and encompassed several diffuse histologic subtypes in the Rappaport classification, the working formulation, and the classification of the Japanese lymphoma study group. However, differences in survival could not be correlated with differences in histologic subtype. All patients presented with Ann Arbor Stage IV lymphoma. Other common clinical features were generalized lymphadenopathy, hepatosplenomegaly, skin and peripheral blood involvement, hypercalcemia, and lytic bone lesions. The clinical course was aggressive with a median survival of 9 months. In two-third of patients with cutaneous involvement, epidermal infiltration resembling Pautrier microabscesses was observed. However, most cases can be readily distinguished from mycosis fungoides/Sézary syndrome on clinical and epidemiologic grounds. The presence of HTLV-antibodies in patients with lymphoid malignancies appears to define a distinct clinicopathologic syndrome which tends to occur in geographic clusters. Adult T-cell leukemia/lymphoma is favored as the diagnostic term for this clinicopathologic entity.

Adult↗
PubMed1984

HTLV: epidemiology and relationship to disease.

With the discovery of the human retrovirus class, an important turning point in the understanding of the process by which cancer is caused and develops in humans has been achieved. As summarized here, clinical and epidemiologic studies have documented the close association of human T-cell leukemia virus (HTLV-I) to a particular form of T-cell malignancy, adult T-cell leukemia/lymphoma (ATL). Yet to be understood is the process involved in translating virus infection into malignant lymphoproliferation. Epidemiologic data suggest that this may involve a relatively long latent period between primary HTLV-I infection and subsequent malignancy risk. Presumably, identifiable co-factors will emerge to explain the trigger for malignant transformation. However, the restricted pattern of tumor phenotype suggest that this process is tightly linked to cells for which HTLV-I has a particularly strong infectious trophism. Interdisciplinary studies are currently under way in a number of laboratories to elucidate the molecular interactions in the HTLV-I associated malignant transformation process in order to correlate these with the epidemiologic data. Thus, lessons are likely to be learned from these molecular and epidemiologic studies which may provide new and important etiologic insights applicable to the prevention and therapy of cancer. Furthermore, with the recent discovery of HTLV-III, a cytopathic form of this class of human retrovirus, the likely cause of acquired immunodeficiency syndrome (AIDS) has been discovered. This has enormous public health implications for the detection, treatment, and prevention of this major medical epidemic. Epidemiologic studies are currently under way to identify what factors associated with virus exposure result in the full-blown AIDS syndrome. In addition, the malignancy potential of this new type of retrovirus is currently the subject of intensive investigation.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Antibodies against human T-cell leukemia/lymphoma virus (HTLV) and expression of HTLV p19 antigen in relatives of a T-cell leukemia patient originating from Surinam.

Serum and peripheral blood cell samples from eleven relatives of a T-cell leukemia patient with human T-cell leukemia/lymphoma virus (HTLV)-associated disease, were investigated for the presence of HTLV antibody and antigen expression. In addition to the patient, three family members were seropositive and a wide range in HTLV antibody titer was observed. The father of the patient showed the highest titer (173,000) and carried HTLV p19+ cells in his peripheral blood. Upon induction of proliferation of these cells by short-term culture in the presence of phytohemagglutinin (PHA) and 12-O-tetradecanoyl phorbol-13-acetate (TPA), an increase from 1% to 28% HTLV p19+ cells was observed confirming previous findings that HTLV p19 expression was correlated with proliferative activity of the host cells. In none of the other seronegative or seropositive relatives of the patient HTLV p19 expression was revealed when tested in freshly isolated mononuclear cells, upon short-term incubation in PHA + TPA or after prolonged culture for 2 or 3 passages in medium containing T-cell growth factor. The results from HLA typing studies did not provide any evidence for HTLV related abnormalities in haplotype expression. Our data confirmed the earlier notion of a prevalence of HTLV infection within families of patients with HTLV-associated disease. It is furthermore obvious from our results that a normal individual may possess high titer HTLV antibody and circulating HTLV p19+ cells without showing signs of disease.

Antibodies, Viral↗
PubMed1983

The human T-cell leukemia-lymphoma virus in the southeastern United States.

The human T-cell leukemia-lymphoma virus (HTLV) is a recently described RNA tumor virus associated with human T-cell malignant neoplasms. In two geographic areas, Japan and the Caribbean basin, clusters of adult T-cell leukemia-lymphoma are "sentinel diseases" and have suggested an underlying prevalence of HTLV infection in both family members of the index cases and in the population. Four cases of lymphoma from the United States are described as illustrative of the sentinel disease. Serological studies of families and of a small population sample suggest that HTLV infection is endemic in certain parts of the southeastern United States at rates similar to those seen in Caribbean blacks but at a lower rate than that observed in southwestern Japan.

Adult↗
PubMed1983

Clinical course of retrovirus-associated adult T-cell lymphoma in the United States.

We studied the clinical features of 11 patients with adult T-cell lymphoma associated with the human T-cell lymphoma virus. The patients were predominantly young, black, and born in the southeastern United States. They had an aggressive course, with the rapid onset of disseminated skin lesions or symptoms related to hypercalcemia and other metabolic disturbances, or both. Common findings included rapid enlargement of peripheral, hilar, and retroperitoneal lymph nodes, with sparing of the mediastinum; invasion of the central nervous system, lungs, or gastrointestinal tract; and opportunistic infections. A paraneoplastic syndrome characterized by increased bone turnover, abnormal bone scintigraphy, and hypercalcemia was present in all patients. Intensive combination chemotherapy produced prompt complete clinical remissions, which were generally of short duration. Similar features have been described in patients in Japan and the West Indies who had adult T-cell lymphoma, which is also associated with the human T-cell lymphoma virus. This syndrome should be suspected in patients presenting with the acute onset of widespread T-cell lymphoma in association with metabolic bone disease and hypercalcemia. The presence of the syndrome can be confirmed by appropriate serologic and virologic studies.

Adult↗
PubMed1983

Human T-cell leukaemia/lymphoma virus-associated lymphoreticular neoplasia in Jamaica.

19 (34%) of 56 Jamaicans with lympho-proliferative neoplasia had antibody to the human T-cell leukaemia/lymphoma virus (HTLV) in their sera. 17 of those positive had either non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukaemia. Of 16 consecutive patients presenting with NHL, 11 (69%) were HTLV seropositive. Virus-positive patients with NHL, among whom females were over-represented, had the clinical features and poor survival typical of adult T-cell leukaemia/lymphoma. HTLV-associated leukaemia/lymphoma is a distinct clinicopathological entity, and the high incidence in this series suggests that HTLV is an important cause of lymphoreticular neoplasia in Jamaica.

Adult↗
PubMed1983

Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS).

Several isolates of a human type-C retrovirus belonging to one group, known as human T-cell leukemia virus (HTLV), have previously been obtained from patients with adult T-cell leukemia or lymphoma. The T-cell tropism of HTLV and its prevalence in the Caribbean basin prompted a search for it in patients with the epidemic T-cell immune deficiency disorder known as AIDS. Peripheral blood lymphocytes from one patient in the United States and two in France were cultured with T-cell growth factor (TCGF) an shown to express HTLV antigens. Virus from the U.S. patient was isolated and characterized and shown to be related to HTLV subgroup I. The virus was also transmitted into normal human T cells from umbilical cord blood of a newborn. Whether or not HTLV-I or other retroviruses of this family with T-cell tropism cause AIDS, it is possible that patients from whom the virus can be isolated can also transmit it to others. If the target cell of AIDS is the mature T cell as suspected, the methods used in these studies may prove useful for the long-term growth of these cells and for the identification of antigens specific for the etiological agent of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Monoclonal antibody against human T cell leukemia virus p19 defines a human thymic epithelial antigen acquired during ontogeny.

Using monoclonal antibody 12/1-2 against a 19,000-dalton human T cell leukemia virus (HTLV) protein (anti-p19), previously demonstrated to be reactive with HTLV-infected human cells, but not in numerous other uninfected cells, we found a reactive antigen to be expressed on the neuroendocrine component of human thymic epithelial cells but not on any other normal epithelial or neuroendocrine human tissues. Moreover, this reactive antigen is acquired on neuroendocrine thymic epithelium during thymic ontogeny--first appearing on fetal thymic epithelial cells between 8 and 15 wk gestation. While only a portion of thymic epithelial cells in the subcapsular cortical region of 15- and 24-wk fetal thymuses contained anti-p19+ epithelial cells, the entire subcapsular cortical region of newborn thymus epithelium was anti-p19+. By age 3 yr, normal subjects' entire subcapsular cortical and medullary thymic epithelium was anti-p19+. Using antibody against HTLV core protein, p24, and c-DNA probes for HTLV DNA, neither HTLV-specific p24 protein nor proviral DNA could be demonstrated in anti-p19+ thymic epithelial tissue. However, thymic epithelial extracts, disrupted HTLV extracts, as well as purified HTLV p19 antigen all inhibited the binding of anti-p19 antibody to thymic epithelium. Thus, anti-p19 may recognize a determinant on an HTLV-encoded 19,000-dalton structural protein that is shared by human thymic epithelium. Alternatively, anti-p19 defines a host encoded protein that is selectively expressed by normal thymic epithelium, and is induced to be expressed in HTLV-infected malignant T cells.

Adolescent↗
PubMed1983

Evidence for human T cell lymphoma-leukemia virus infection of family members of human T cell lymphoma-leukemia virus positive T cell leukemia-lymphoma patients.

Sera of family members of patients from the United States, the Caribbean, and Japan, with human T cell lymphoma-leukemia virus (HTLV) associated T cell malignancies, possess HTLV-specific antibodies directed against internal structural components of HTLV, p24 and p19. The prevalence of antibodies to HTLV is greater in family members than in random healthy donors, which supports the infectious nature of HTLV and its association with particular aggressive T cell malignancies. Expression of HTLV p24 and p19 has also been observed in cultured T cells of some healthy relatives, and intact virus particles have been released from cells of one possibly pre-leukemic family member.

Antibodies, Neoplasm↗
PubMed1983

High incidence of human type-C retrovirus (HTLV) in family members of a HTLV-positive Japanese T-cell leukemia patient.

Sera and peripheral blood cells of an adult T-cell leukemia patient and several clinically normal members of his family from the northwest coast of Japan were examined for evidence of infection with human T-cell leukemia (lymphoma) virus (HTLV). The sera of the patient and his parents had antibodies to HTLV, whereas these antibodies were absent in the sera of the patient's brother and sister. T-cell lines were established from the peripheral blood lymphocytes of all of the family members, and all except the patient's sister expressed HTLV antigens (p19, p24, and reverse transcriptase) and type-C virus particles. Not only the fresh peripheral blood lymphocytes from the patient but also those from his clinically normal mother showed abnormal morphology of the kind characteristic of some patients with T-cell leukemia. These studies are consistent with previous evidence indicative of a high rate of HTLV infection within families, and they show that people whose sera are negative for antibodies may still be infected by HTLV. In addition, the results indicate that infection of T cells by HTLV can be associated with morphological transformation of the cells without other signs of leukemia.

Humans↗
PubMed1983

Human T-cell leukemia/lymphoma virus: the retrovirus of adult T-cell leukemia/lymphoma.

Human T (thymus-derived)-cell leukemia/lymphoma virus (HTLV) is a new retrovirus first isolated from T-cell lines from a patient with cutaneous T-cell lymphoma from the southeastern United States. Closely related viruses have since been isolated from several patients with adult T-cell leukemia and lymphoma (and some normal persons) from different areas of the world. HTLV is not a genetically transmitted endogenous virus of humans, but it rather is acquired by postzygotic infection. Natural antibodies to several purified viral proteins have been observed in infected individuals. HTLV is transmissible in vitro to human cord blood T cells, and infection results in an increased growth rate, a reduced requirement for (and often independence from) T-cell growth factor, and an abrogation of the crisis period that usually occurs a month after the establishment of normal T-cell cultures. These data suggest that HTLV is the etiologic agent in some human cases of leukemia and lymphoma.

Antibodies, Viral↗