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Biomedical subjects

T E Mandel

Publications and source records attributed to T E Mandel.

At least 181 records · Page 10Linked to original sources
PubMed1980

Resistance and susceptibility of mice to bacterial infection: histopathology of listeriosis in resistant and susceptible strains.

C57BL/10 mice have previously been shown to be 100 times more resistant to intravenously injected Listeria monocytogenes than are BALB/c mice due to the action of a single gene, Lr. Differences in the histopathology of listeriosis in the two strains were sought. Of the tissues examined, only liver, spleen, blood, and thymus showed changes. In the liver, Listeria localized in Kupffer cells within 3 h of infection. By 24 h these cells became surrounded by neutrophilic polymorphonuclear leukocytes. After high doses of Listeria, the susceptible BALB/c mice showed many foci surrounded by few polymorphs, whereas in the resistant C57BL/10 mice there were relatively few foci surrounded by many polymorphs. By 4 days in sublethally infected mice the polymorphs in the liver of both strains were being replaced by monocytes and macrophages. Liver morphology returned to normal by 8 days postinfection. In the blood of both strains there was a rise in total lymphocyte numbers at 24 h, followed by a fall in T-lymphocytes and recovery at 5 days. C57BL/10 mice showed an early monocytic response in the blood, whereas BALB/c mice showed a polymorph leukocytosis. In the spleens of both C57BL/10 and BALB/c mice there was an early neutrophil response and red pulp hyperemia. This was followed by a dramatic lymphocyte depletion in the T-dependent periarteriolar regions in both strains beginning 2 days after infection. Absolute numbers of Thy-1(+) cells in spleen cell suspensions also fell to 10% of normal, recovering 6 to 8 days postinfection. Surface immunoglobulin-positive B-lymphocytes and Thy-1(-), immunoglobulin-negative "null" cells rose in both strains at days 4 to 5, returning to normal levels on days 10 to 12. Whether the null cells represent lymphocytes or other cell types remains unresolved. Thymus atrophy was seen in the BALB/c mice but not in C57BL/10 mice.

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PubMed1980

The presence of mast cells in agar cultures.

Using a specific stain and electron microscopy, small numbers of mast cells were detected in human bone marrow cultures. However, they were not detected in agar cultures containing murine bone marrow cells. In bone marrow cultures from three patients with acute myeloid leukemia the number of mast cells was elevated.

Agar↗
PubMed1980

Use of spleen organ cultures to monitor hemopoietic progenitor cell regeneration following irradiation and marrow transplantation.

After lethal irradiation of C57BL mice followed by the injection of 10(7) marrow cells, total cellularity and progenitor cell levels exceeded pretreatment levels within 12 days in the spleen, but regeneration remained incomplete in the marrow. The exceptional regenerative capacity of progenitor populations in the spleen was observed in organ cultures of spleen slices prepared 24 hr after irradiation and transplantation, excluding continuous repopulation from the marrow as a significant factor in splenic regeneration.

Animals↗
PubMed1980

Immune elimination and immune retention: the relationship between antigen retained in the foot and the elicitation of footpad swelling.

We determined whether (1) long term antigen retention is present in distal sites after footpad challenge of immune mice; (2) if antigen retained in the foot is selectively localized; and (3) if the foot is adversely affected by the retained antigen. Mice immune or non-immune to human serum albumin (HSA) were injected in the hind footpads with 125I-HSA. In immune mice rapid clearance of radiolabel occurred in the liver, lungs, kidney, blood and urine but radiolabel was retained in the hind feet, draining lymph nodes and spleen. Non-immune mice rapidly cleared radiolabel from these sites. Autoradiography revealed that most of the radiolabel in the feet was in flexor tendons and tendon sheaths. Electron microscope autoradiography indicated that antigen was associated with collagen at the tendon surface, but not with cells or cell processes. Radiolabel solubilized from the feet, lymph nodes and spleen could be specifically precipitated with rabbit anti-HSA. Histological examination of the tendon and surrounding tissues did not show that retained antigen was causing inflammation or chronic tissue damage. Nanogram levels of antigen could elicit swelling in the sensitized foot even if the antigen was injected at a remote site, but mice immunized by other routes or against other antigens did not show footpad swelling. Antigen retained on collagenous tissues may induce hypersensitivity and thus play a role in rheumatic diseases.

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PubMed1980

Antibody isotypes mediating antigen retention in passively immunized mice.

Antibody isotypes vary in their capacity to mediate retention of a readily catabolized protein antigen, human serum albumin (HSA) in spleen, popliteal lymph node (PLN) and hind foot. Hyperimmune anti-HSA mouse sera were separated into fractions highly enriched for IgM, IgG1 and IgG2 via differential elution from protein A-Sepharose. These fractions were used to immunize normal mice passively. Twenty-four hours later the mice were injected with radio-iodinated HSA into the hind footpad. When the amount of HSA retained in the spleen 6 days later was determined, the potency of various antibody fractions to mediate retention could be ranked IgG2=IgG1 > IgM. The amount of HSA retention mediated by various fractions correlated well with autoradiographic evidence demonstrating localization of HSA in splenic follicles. The localization pattern in PLN was similar to the spleen except that the IgM-containing fraction mediated follicular localization of HSA to a considerable degree. In tendons of the hind foot, IgG1 mediated HSA retention five times better than IgG2 or IgM fractions. The amount of radioactivity found in the liver varied inversely with HSA retention in other locations. The results demonstrate differences in antibody isotype requirements for antigen localization in spleen, regional lymph node and collagenous sites of the hind foot.

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PubMed1979

Colony formation in agar by multipotential hemopoietic cells.

Agar cultures of CBA fetal liver, peripheral blood, yolk sac and adult marrow cells were stimulated by pokeweed mitogen-stimulated spleen conditioned medium. Two to ten percent of the colonies developing were mixed colonies, documented by light or electron microscopy to contain erythroid, neutrophil, macrophage, eosinophil and megakaryocytic cells. No lymphoid cells were detected. Mean size for 7-day mixed colonies was 1,800-7,300 cells. When 7-day mixed colonies were recloned in agar, low levels of colony-forming cells were detected in 10% of the colonies but most daughter colonies formed were small neutrophil and/or macrophage colonies. Injection of pooled 7-day mixed colony cells to irradiated CBA mice produced low numbers of spleen colonies, mainly erythroid in composition. Karyotypic analysis using the T6T6 marker chromosome showed that some of these colonies were of donor origin. With an assumed f factor of 0.2, the mean content of spleen colony-forming cells per 7-day mixed colony was calculated to vary from 0.09 to 0.76 according to the type of mixed colony assayed. The fetal and adult multipotential hemopoietic cells forming mixed colonies in agar may be hemopoietic stem cells perhaps of a special or fetal type.

Animals↗
PubMed1979

Immune retention: immunological requirements for maintaining an easily degradable antigen in vivo.

Radioactive human serum albumin (125I-HSA) was injected into the hind foot pads of unimmunized mice, actively immunized mice and mice passively immunized with mouse or rabbit anti-HSA serum. Eleven days later the unimmunized mice had cleared most of the 125I-HSA. In contrast, a high concentration of 125I-HSA was retained in the feet and draining lymph nodes and, to a lesser extent, in the spleen of the actively or passively immunized mice. Although immune retention required specific antibody, it appeared to be independent of T-cells or T-cell factors, since passively immunized nude mice retained antigen as well as actively or passively immunized normal mice. Depletion of the complement system with cobra venom factor (CVF) increased antigen retention in the feet but decreased retention in the spleen. Treatment with CVF did not decrease antigen retention in lymph nodes of actively immunized mice. Such treatment did, however, decrease retention in lymph nodes of passively immunized mice although not to the same extent as in the spleen. Retention of antigen in the feet was not only complement-independent but was also Fc independent, since F(ab')2 fragments of IgG could mediate immune retention. Antigen dose response studies indicated that immune retention in lymph nodes occurred optimally with minute amounts of antigen, whereas optimal retention in the feet required much higher concentrations of antigen. Foot pad injections of non-radiolabelled HSA eliminated 60% of the radioactivity retained in the foot pads of immunized mice. In contrast, non-radioactive egg albumin (EA) had almost no effect on retained HSA. However, if the mice were immunized to both EA and HSA, an injection of EA would displace a significant amount of retained HSA. Complexes of one specificity can apparently displace some retained antigen of a differing specificity.

Animals↗
PubMed1978

Suppression of an in vitro humoral immune response by cultured fetal thymus cells.

We studied the function of fetal thymocytes, derived from thymus progenitor cells of 14-day-old fetuses in an organ culture system, in an in vitro humoral immune response. The unprimed cultured fetal thymocytes suppressed the T-dependent primary immune response to adult syngeneic spleen cells against sheep red blood cells, but failed to suppress the response against the T-independent antigen NIP-POL [4(hydroxy-3-iodo-5-nitrophenyl)acetyl-coupled polymerized flagellin]. The suppression was abolished by anti-Thy-1 serum and complement treatment. Using a differential killing procedure, the suppressor cells were characterized as "low" Thy-1 cells. In addition, they were resistant to hydrocortisone. Suppression could only be achieved when the cultured fetal thymocytes were added during the first 48 h of culture, suggesting that their action occurred during the induction phase of the response. The implications of the high frequency of suppressor cells during fetal life are discussed.

Animals↗
PubMed1978

Haemopoietic stem cells in the foetal mouse thymus.

The presence of haemopoietic stem cells (HSC) in the foetal mouse thymus was assessed to determine whether all cells which enter the developing organ are precommitted to thymocyte differentiation, or if stem cell multipotentiality still exists. The Till and McCulloch spleen colony assay was used to delineate foetal-thymus derived HSC in lethally irradiated recipients. Of the range examined, between 13 days of gestation to birth, a peak of stem cell activity occurs in 15-day foetal thymus. The surface colonies produced by the thymus-derived HSC are small compared to colonies produced by the liver derived HSC, although well within the range of the latter. Histologically, five types of colonies were identifiable which were produced by the thymus-derived HSC, indicating that these cells retain the potential to form a wide range of differentiated colonies.

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