Search PubMed⌕ Search

Biomedical subjects

H R Miller

Publications and source records attributed to H R Miller.

At least 163 records · Page 9Linked to original sources

Pseudomembranous colitis: isolation of two species of cytotoxic clostridia and successful treatment with vancomycin.

Lincomycin-resistant Clostridium sporogenes obtained from the stools of a patient with lincomycin-associated pseudomembranous colitis produced a heat-stable cytotoxin in low titre when grown in chopped meat medium. Vancomycin eradicated this strain and all other clostridia, and controlled the symptoms. When diarrhea recurred 7 days after treatment with vancomycin was stopped, clostridia including C. sporogenes and C. difficile were again isolated. The C. difficile produced a heat-labile cytotoxin in high titre that was unaffected by growth in various media and induced colitis in hamsters. Treatment with vancomycin, to which all the clostridia were sensitive, eradicated both toxic species and controlled the diarrhea. Antibiotic-induced pseudomembranous colitis may be associated with more than one species of toxin-producing clostridia. Vancomycin therapy should be continued for 10 days or more in patients with severe disease to eradicate the responsible organism.

Aged↗

Reassortment of lymphocytes in lymph from normal and allografted sheep.

The distribution and nature of surface immunoglobulin-bearing (SIg) cells were studied in various sources of lymph from normal sheep and from sheep bearing renal autografts and renal allografts. In normal sheep, 12.2% +/- 1.5 of all mononuclear cells in peripheral lymph SIg and, of these, more than 50% were monocytes and macrophages. Less than 6% of the lymphocytes in peripheral lymph carried SIg. In contrast, 24.7% +/- 1.3 of the mononuclear cells in central lymph had SIg, and all of the labeled cells were lymphocytes. The frequencies of SIg cells in peripheral lymph issuing from renal autografts and from renal allografts were 6.7% +/- 1.3 and 6.9% +/- 0.8, respectively, and the labeled cells were predominantly lymphocytes. The proportion of SIg cells in central lymph from graft-bearing sheep was similar to that from normal sheep. The differences between central lymph and peripheral lymph from both normal and graft-bearing sheep are thought to reflect a restriction on the passage of SIg cells through capillary endothelium in nonlymphoid tissues.

Animals↗

Leukocyte-dependent antibody in sheep immunized with murine mastocytoma cells.

Sheep serum removed after hyperimmunization with murine P-815 mastocytoma cells was fractionated and two types of cytotoxic antibody were isolated. Complement-dependent antibody (CDA) was detected in the IgM and IgG1 fractions whereas "leukocyte" -dependent antibody (LDA) was found in the IgG1 and IgG2 fractions. Effector cells that mediated LDA cytotoxicity were isolated from sheep blood but not from sheep lymph, showing that recirculating lymphocytes do not have LDA effector function. Removal of adherent cells from blood leukocyte suspensions reduced antibody-mediated cytotoxicity, suggesting that LDA effector leukocytes may be a heterogenous population containing both adherent and nonadherent cells.

Animals↗

Cytotoxic mechanisms detected in vitro following sheep renal allografts.

Cytotoxic effects of lymph and blood components, removed from sheep following renal allografting were determined by in vitro assay using 51Cr labelled donor sheep lymphocytes as target cells. Lytic antibodies were detected in lymph efferent from the node draining the graft site and at lower concentrations in blood serum and in lymph leaving the graft. The cytotoxic antibodies had both complement-dependent and leucocyte-dependent functions; the complement-dependent antibodies were fractionated and shown to be of IgM and IgG1 subclasses. Cytotoxic cells were found in lymph leaving the graft but not in blood or in lymph efferent from the draining node; those detected in the renal lymph were non-specific in action and their appearance correlated with increased numbers of macrophages.

Animals↗

Synthesis of antibody and immunoglobulins without detectable antibody function in cells responding to horseradish peroxidase.

The kinetics of immunoglobulin-synthesizing cells (IFC) and antibody-forming cells (AFC) are compared in the popliteal nodes of mice challenged, in the hind footpads, with horseradish peroxidase (PO) in Freund's complete adjuvant. A rise in the number of IFC without antibody function precedes the appearance of AFC. IFC reach peak numbers 7 days before AFC. Control experiments show that the majority of IFC without antibody function are responding to PO and not to adjuvant. Kinetic and radioautographic data suggest that IFC arise by division and differentiation; however, the doubling time of AFC is too rapid to be accounted for by cell division alone. Double staining techniques revealed the presence of immunoglobulin and antibody in different compartments of the same cell in 5 to 15% of the AFC. It is postulated that some AFC are recruited, possibly from cells already synthesizing immunoglobulin determinants.

Animals↗

Intracellular distribution of antibody in immunocytes responding to primary challenge with horseradish peroxidase.

A new improved technic was used to follow the development of, and the intracellular antibody distribution in antiperoxidase antibody-forming cells (AFC) of the mouse popliteal lymph nodes responding to primary stimulation with horse-radish peroxidase (HRP). The first AFC were found 6 to 8 days after immunization and were all plasma cells. Antibody was concentrated in the Golgi complexes and in a few cisternae of rough endoplasmic reticulum. Subsequently, an increasing proportion of the AFC were filled with antibody, and with time the numbers of full cells and the intensity with which they stained increased. Kinetic studies of the cell changes in the lymph node medulla suggest that lymphoid cells proliferate, differentiate into plasma cells, and are then recruited as AFC. Furthermore, it was concluded that the changing intracellular distribution of antibody represents the gradual filling of the AFC with specific antibody.

Animals↗

Intracellular distribution of antibody in immunocytes responding to secondary challenge with horseradish peroxidase.

A new improved immunoperoxidase method was used to study the antiperoxidase antibody-forming cells (AFC) in the medullae of mouse popliteal nodes after a second challenge with horseradish peroxidase (HRP). Two populations of AFC were found: a) A stable nondividing background population of mature plasma cells whose content of antibody increased 3 days after challenge and b) A new population of cells which increased in number exponentially between 18 hours and 5 days after challenge. In contrast with the first response, the new AFC included many stimulated lymphoid cells, significant numbers of small lymphocytes, and plasma cells. The results suggest that the morphology of the AFC found in the first and second responses reflects the stage in their developmental cycle at which the precursor cells are recruited into the AFC population. More than 90% of the AFC arising between 18 hours and 3 days after challenge had antibody in their perinuclear cisternae, and their cisternae of rough endoplasmic reticulum were rapidly filled with antibody. The striking differences between the intracellular localisation of antibody during the first and second responses are discussed.

Animals↗

Immune reactions in mucous membranes. IV. Histochemistry of intestinal mast cells during helminth expulsion in the rat.

The histochemistry of intestinal (IMC) and connective tissue mast cells (CTMC) in the normal rat is compared. Acid mucopolysaccharide appears to be less strongly sulfated and the granule content of monoamines is lower in IMC. After infection with the intestinal helminth, Nippostrongylus brasiliensis, the mucosal content of IMC is altered. During the early phase of immunologic expulsion of this parasite (self-cure) the IMC proliferate and differentiate; the histochemical properties of the granules appear to reflect this process. Very large numbers of mature IMC are found in the mucosa during the later, rapid phase of worm expulsion. Both acid mucopolysaccharide and monoamines are depleted from the granules of these cells; this is consistent with previous studies suggesting that IMC discharge occurs at this stage. These findings lend further support to the hypothesis that the biogenic products of IMC discharge are responsible for the increase in mucosal permeability which occurs during self-cure and which may facilitate the rapid translocation of antiworm antibody into the intestinal lumen.

Animals↗