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Biomedical subjects

D Mann

Publications and source records attributed to D Mann.

At least 145 records · Page 8Linked to original sources

Transformation of human umbilical cord blood T cells by human T-cell leukemia/lymphoma virus.

Several isolates of human T-cell leukemia/lymphoma virus (HTLV) were transmitted to normal human T cells obtained from the umbilical cord blood of newborns. T cells from seven specimens were immortalized by infection with different HTLV isolates and their properties were compared with those of activated uninfected normal T cells grown in the presence of T-cell growth factor (TCGF) and with those of HTLV-positive neoplastic T-cell lines derived from patients with T-cell malignancies. The HTLV-infected cells generally belonged to a class of mature T cells (OKT4+ and Leu 3A+) and differed from the normal uninfected cells in that they could be propagated in culture indefinitely; possessed altered morphology, including convoluted nuclei and some bi- and multinucleated giant cells; formed large clumps in culture; demonstrated a diminished requirement for TCGF; had an increased density of TCGF receptors; often became completely independent of exogenous TCGF; and expressed HLA-DR determinants. These properties of the HTLV-infected cord blood T cells contrasted to those of uncultured cord blood T cells and of cord blood cells stimulated with mitogen and grown with TCGF but resembled the characteristics of T-cell lines established previously from patients with HTLV-associated T-cell malignancies. This in vitro system offers a unique opportunity to study the basic mechanism involved in abnormal growth and neoplastic transformation of a specific class of human T cells.

Cell Division↗

Natural killer cells in mouse lung: surface phenotype, target preference, and response to local influenza virus infection.

Natural killer (NK) and natural cytotoxic (NC) cells can be recovered from the spleens of mice. NK/NC cells are thought to serve as a first line of defense (before the development of immune responses) against tumor and virus infected cells; therefore organs such as the lung that are exposed to the environment may harbor NK/NC cells. Studies reported in this manuscript characterize a population of pulmonary cells (recovered from collagenase-treated lungs) that exhibited cytotoxic activity against 51Cr-labeled tumor targets in vitro. As with the spleen cell populations, the mononuclear cells from the lung lysed the NK-sensitive target YAC-1 as well as the NC-sensitive WEHI 164.1 tumor cells in vitro. By using flow cytometry, it was observed that 15 to 20% of nylon wool-passed (NWP) lung cells and 5 to 15% of NWP spleen cells from C57BL/6 mice could bind antibody for NK cell alloantigens (NK 1.2, defined by (CE X NZB)F1 anti-CBA sera). Treatment of lung and spleen cell populations with complement and antisera to NK 1.2, asialo GM1, and Ly-5 but not Thy-1 antigens significantly decreased lung and splenic NK (YAC-1) activity. Forty-eight hours after infection of mice by intratracheal inoculation of an infectious dose of influenza virus (PR/8/34) NK activity was stimulated in the lung and not the spleen. Therefore although NK cells in the lung and spleen are similar in antigenic phenotype and target preference there appears to be a pulmonary compartment of natural resistance cells the function of which can be modulated locally. These data are consistent with the hypothesis that the lung contains a separate compartment for NK/NC cells that may participate in the defense mechanisms of the lung.

Animals↗

Human T-cell leukemia-lymphoma virus (HTLV) is in T but not B lymphocytes from a patient with cutaneous T-cell lymphoma.

A human type C retrovirus, designated HTLV, previously was isolated from or identified in some patients with leukemias and lymphomas of mature T lymphocytes. HTLV is genetically and serologically distinct from any known animal retroviruses. The absence of HTLV proviral sequences in DNA from normal humans showed that HTLV is not a ubiquitous endogenous (germ-line transmitted) virus of humans. Antibodies to HTLV core proteins have been identified in some people with T-cell neoplasias and are particularly prevalent in Japanese with adult T-cell leukemia, suggesting that HTLV is acquired horizontally. However, it was possible that HTLV is transmitted through the germ line of some (possibly rare) families and is then expressed in the HTLV- positive malignancies. An opportunity to study this question was provided by the development of several T-cell lines and a B-cell provided by the development of several T-cell lines and a B-cell line from one HTLV-positive patient with a cutaneous T-cell lymphoma. Here we report that HTLV proteins or nucleic acids (or both) are found in three independently derived T-cell lines, all shown by HLA typing to have originated from the patient. In contrast, the B-cell line, the identity of which was also ascertained by HLA typing, contained no detectable HTLV protein, RNA, or proviral DNA. Because the sensitivity of the latter assay is more than sufficient to detect one proviral equivalent per haploid genome, the results indicate that HTLV was not transmitted to this patient through the germ line but rather was acquired by infection.

B-Lymphocytes↗

[Determination of serum haptoglobin concentration in the acute phase of myocardial infarct by means of Mancini's simple radial immunodiffusion test].

In 14 patients with an according to the WHO-criteria definitive myocardial infarction quantitative serum haptoglobin course controls were performed in the first week after the pain event. The haptoglobin estimations were performed by means of simple radial immunodiffusion after Mancini on M-partigen plates. Up to the fifth day after the pain event an increase of the haptoglobin concentration could be established. On the two following days a decreasing tendency could be observed. In a comparative group of five with chronic ischaemic heart diseases and angina pectoris syndrome under the same conditions of examination no increase of haptoglobin could be observed during the first five days after the pain event. These examination results correspond with the literary data, that in disease with tissue destruction increases of haptoglobin are to be observed.

Coronary Disease↗

The structure of the cercal sensory system and ventral nerve cord of Grylloblatta. A comparative study.

The structure of cercal sensilla, the cercal nerve and the central projections of the cercal sensory nerve of a notopteran (Grylloblatta sp.) are described and compared with other orthopteroid insects in which the cercal sensory system and central connections are well known. The cercal sensilla are similar to those of gryllids and blattids, but the gross structure of the cerci and distribution of cercal sensilla more closely resemble those of the Thysanura. The elements of the cercal sensory nerves and the central nervous system are similar to those of other orthopteroid insects, but extracellular material is present in greater quantity, and more extensive glial bundling of axons occurs in both the cercal nerve and central connectives. Glial structure, extracellular material and large multicristate mitochondria may be adaptations to life near O degrees C. The form of central projections of the cercal nerve and the configuration of the largest abdominal interneurons are unlike those of gryllids and Dictyoptera; they are similar to those of Dermaptera.

Abdomen↗

Cell surface differentiation antigens of the malignant T cell in Sezary syndrome and mycosis fungoides.

Using a panel of monoclonal antibodies and rabbit heteroantisera, we have studied the cell surface markers of peripheral blood (PB) Sezary cells from six patients with mycosis fungoides or Sezary syndrome, disease grouped within the spectrum of cutaneous T cell lymphomas (CTCL). Furthermore, we have studied two cell lines (Hut 78 and Hut 102) derived from malignant Sezary T cells from CTCL patients. The monoclonal antibody 3A1 defines a major human PB T cell subset (85% of PB T cells) while the antigen defined by the monoclonal antibody 4F2 is present on a subset (70%) of activated PB T cells and on circulating PB monocytes. In contrast to normal subjects in whom 60-70% of circulating PB mononuclear cells were 3A1(+) T cells, PB mononuclear cells from six CTCL patients studied had an average of only 10.6+/-3.2% 3A1(+) T cells. Whereas 85% of E-rosette positive cells from normal individuals were 3A1(+), virtually all E-rosette positive T cells from the Sezary patients were 3A1(-). Two patients with high numbers of circulating Sezary T cells had both aneuploid and diploid PB T cell populations present; after separation of PB T cells into 3A1(+) and 3A1(-) cell suspensions, all 3A1(-) cells were found to be aneuploid. In contrast to normal resting PB T cells which were 4F2(-), all PB Sezary cells were 4F2(+), suggesting a state of activation. The 3A1 antigen was on a variety of acute lymphoblastic leukemia T cell lines (HSB-2, RPMI-8402, MOLT4, CEM) but was absent on the Hut 78 and Hut 102 Sezary T cell lines. Using rabbit anti-human T and anti-human Ia (p23, 30) antisera, we found that all malignant Sezary PB cells tested were killed by anti-T cell antiserum plus complement but not by anti-Ia plus complement. In contrast, Sezary cell lines Hut 78 and 102, were killed by both anti-T cell antiserum and anti-Ia plus complement. Similar to 3A1(-) normal PB T cells, 3A1(-) Sezary PB T cells proliferated poorly to phytohemagglutinin and concanavalin A. However, 3A1(-) Sezary T cells were able to provide T cell help towards pokeweed mitogen-induced in vitro B cell immunoglobulin synthesis, an immunoregulatory function limited to 3A1(+) T cells in normal subjects.Thus, the 3A1 antigen is present on 85% of normal PB T cells, and on most T-acute lymphoblastic leukemia lines tested; in contrast the 3A1 antigen is not present on the majority of circulating malignant Sezary PB T cells nor on T cell lines derived from malignant Sezary T cells. The lack of expression of the 3A1 antigen may be associated with malignant transformation of T cells in CTCL and may be an important marker for tracing the clonal origin of the malignant Sezary T cell.

Adult↗

[Long-term studies on the beta blocker talinolol (cordanum) with special reference to side effects].

224 patients with coronary heart disease, hypertension, disturbances of cardiac rhythm or hyperkinetic heart syndrome were treated with the cardioselective beta-blocker Talinolol (Cordanum) for a period up to 3 years. In 239 examinations in intravenous or peroral application of this medicament we controlled among others the appearance of side effects. This test was carried out with the help of standardised questionings and clinical controls. Apart from registrations of ECG and blood pressure clinico-chemical investigations were included and in the long-term experiment also tests by dermatologists, otorhinolaryngologists and ophthalmologists. In the total number of patients the proportion of side appearances was 17,6%, in the long-term experiment (100 patients with on an average 12.9 months) 7%. The symptoms most frequently cited in the initial phase, such as fatigue, weakness, insomnia and nausea receded within 4 weeks apart from few exceptions. There did not appear any essential bradycardic disturbances of the cardiac rhythm, just as little were references to disadvantageous reactions in the sense of a practolol syndrome.

Adolescent↗

Dopaminergic neuronal responses to a non-amphetamine CNS stimulant.

The present study compares the effects of d-amphetamine (d-AMP) and the potent non-amphetamine CNS stimulant, amfonelic acid (AFA), on the firing rate of single midbrain dopaminergic (DA) neurons and on neostriatal DA metabolism (dihydroxyphenylacetic acid--DOPAC). The results indicate that AFA, like d-AMP, reduces the firing rate of DA neurons, although unlike d-AMP, AFA does not cause a decrease in neostriatal DOPAC content and, in fact, enhances that produced by haloperidol (HALO). The AFA-induced decrease in firing rate, like d-AMP, is reversed by the DA receptor blocker HALO, but again unlike d-AMP, the decrease in firing rate is not prevented by catecholamine synthesis inhibition with alpha-methyl-para-tyrosine. Thus, both amphetamine and amfonelic acid have identical electrophysiological effects on DA neurons but act by different mechanisms.

3,4-Dihydroxyphenylacetic Acid↗

Concanvalin-A-binding proteins on the surface of human malignant and normal lymphocytes.

The concanavalin-A-binding cell surface glycoproteins from normal and certain leukaemic human lymphocytes were radiolabelled and then solubilized with detergent, isolated by affinity chromatography on Con A insolubilized on agarose beads, and subsequently analysed by SDS-polyacrylamide gel electrophoresis. Leukaemic T cells from patients with Sezary syndrome were found to express major concanavalin-A-binding glycoproteins on their outer surface similar to those of normal T lymphocytes. Leukaemic B cells from patients with chronic lymphocytic leukaemia expressed Con-A-binding proteins similar to those of B-cell lines. HLA antigens were predominant among the major Con-A-binding proteins on the surface of the normal and the malignant T cells studied. Human Ia-like antigens, HLA antigens, and the cell surface immunoglobulins IgD and IgM represented the major Con-A-binding proteins on the B cells studied. beta 2-microglobulin was found associated with HLA antigens on both leukaemic and non-leukaemic T and B cells. The presence of additional Con-A-binding proteins expressed on the surface of the different cell types studied is discussed along with some physical characteristics of the human Ia-like antigens isolated.

B-Lymphocytes↗

Action of prostaglandins on heart arrhythmias.

Depending on the type applied, prostaglandins have different cardiovascular effects both with regard to blood pressure and inotropic action. Results from experiments on animals show that the antiarrhythmic effect seems to be relatively uniform. So far our own clinical investigations have been carried out on 18 patients with disturbances of the heart rhythm predominantly due to organic causes. The response to PGF2 alpha infusions in dosages of 0.5-3.0 mg was not uniform. At constant heart rates, transitory regression of distrubances in the heart rhythm occurred, most pronounced in ventricular extrasytoles. Positive results became particularly evident in patients suffering from myocardial infarction, partially coinciding with the administration of cardiac glycosides. The antiarrhythmic effects cannot be explained by non-specific quinidine-like actions which was also confirmed by the lacking prostaglandin action on the diastolic stimulus threshold.

Adult↗

Partial purification of detergent-soluble HL-A antigen and its cleavage by papain.

HL-A antigen solubilized with the non-ionic detergent, Brij 99, has been purified to about 50% of homogeneity from a cultured human lymphoblast line. It consists of two nonidentical subunits of 44,000 and 12,000 molecular weight (MW). Upon papain proteolysis the 44,000 MW peptide is converted by at least two cleavages to a 34,000 MW peptide, but the 12,000 MW peptide appears to be unchanged. Concomitantly, the apparent molecular weight in gel filtration chromatography under nondenaturing conditions in the presence of Brij 99 is reduced from 460,000 to 45,000. HL-A molecules produced by direct papain proteolysis of membranes and by papain treatment of purified detergent-soluble HL-A are identical.

Animals↗