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Biomedical subjects

H R Miller

Publications and source records attributed to H R Miller.

At least 145 records · Page 8Linked to original sources

Generation of mucosal mast cells is stimulated in vitro by factors derived from T cells of helminth-infected rats.

The connective tissue of rats, and several other species of mammals, contains two distinct types of mast cells that differ in morphology, histochemical staining properties and location1. One type, frequently called the normal connective tissue mast cell, can be obtained in nearly homogeneous preparation from a mixed cell population in the peritoneal cavity and forms the basis of our knowledge of mast cells. The other type is referred to as the mucosal mast cell because in normal rats it has been observed only in mucosal tissue. Infection with helminth parasites induces an exteNsive accumulation of mast cells and eosinophils in the tissues, and parasites of mucous surfaces, in particular, stimulate a rapid hyperplasia of mucosal mast cells. However, the origin of mucosal mast cells, and their relationship to the connective tissue mast cells is uncertain. We now slow that lymphocytes of helminth-infected rats, on in vitro stimulation with specific antigen, release factors causing pronounced mucosal mastocytosis in normal rat bone marrow cultures.

Animals↗

Interpersonal judgements of schizophrenics: a golden section study.

Normal subjects typically categorize acquaintances on bipolar dimensions consisting of pairs of contrasting descriptive adjectives by using positive adjectives in the golden section ratio, i.e. 62 percent cent of the time. This study compared the performance of thought-disordered and non-thought-disordered schizophrenics on a similar task, using acquaintances and inanimate objects. Subjects generated six evaluatively positive figures (three acquaintances and three objects) and six negative figures (three acquaintances and three objects) and categorized them and themselves using either pole of 12 pairs of contrasting descriptive adjectives. Positive adjectives were assigned to objects 59.2 per cent and to acquaintances 62.8 per cent of the time. Overall, positive adjectives were assigned 61.0 per cent of the time. There were no differences between TD and NTD subjects. Subjects rated acquaintances positively (62.0 per cent) significantly more often than objects (P less than 0.05). Results supported the fundamental nature of the GS in interpersonal relations and the idea that schizophrenics identify with and differentiate themselves from others in the same way as normals.

Adult↗

Quantitative analysis of mucosal mast cell protease in the intestines of Nippostrongylus-infected rats.

Following infection with the intestinal nematode Nippostrongylus brasiliensis, mucosal mast cell (MMC) proliferated in the jejunum and the peak of this response was associated with a nine-fold increase in the level of mucosal mast cell protease (RMCPII) in the mucosa. At this stage the protease constituted 10%-15% of the soluble protein from gut homogenates. Concomitant immunoperoxidase studies showed that during the early proliferation of the MMC, only a proportion of the cells in lamina propria and none of the MMC within the epithelium contained detectable RMCPII. Fourteen and 20 days post infection and following a secondary challenge, staining for RMCPII in lamina propria MMC was much stronger and a few intraepithelial mast cells also contained RMCPII. With time after infection an increasing proportion of intestinal goblet cells were specifically labelled, indicating an accumulation either of RMCPII or of an antigenically similar enzyme within mucous glycoproteins. The significance of the high levels of protease in parasitized gut and of its apparent cellular distribution is discussed in relation to the protective response against the parasite.

Animals↗

Quantitative recovery of isolated mucosal mast cells and globule leucocytes from parasitised sheep.

A method of the quantitative recovery of mast cells and globule leucocytes from the gastric mucosa of parasitised sheep is described. The optimal yields of viable cells from small samples of tissue digested with collagenase and hyaluronidase were measured. Mast cell/globule leucocyte yields were significantly increased in sheep orally challenged with 3000 to 5000 Ostertagia circumcincta per day. In these groups as many as 23 per cent of the cells were mast cells/globule leucocytes. Enrichment of these cells was achieved by Percoll density gradient centrifugation and fractions containing 34 to 84 per cent mast cells/globule leucocytes were isolated.

Abomasum↗

Toxoplasma gondii: its effect on the ovine popliteal lymph node.

Four non-immune sheep and two with naturally acquired antibody were inoculated subcutaneously in the lower part of the leg with 100 cysts of Toxoplasma gondii. Two other non-immune sheep were given a control inoculum. Efferent lymph from the popliteal nodes on the side of the injection was collected via a cannula and injected into mice. Live toxoplasms were present in the lymph of non-immune sheep from day 2 until day 15, at which time the experiment was terminated. Corresponding samples of lymph from the one immune animal tested were almost always negative. Severe pathological changes were present in lymph nodes from non-immune sheep. Gross enlargement, loss of architecture, haemorrhages, and some necrosis occurred, and the sinuses were packed with plasma cells and plasmablasts. Changes in the nodes of immune sheep were similar but less striking, with retention of architecture, no haemorrhages and no necrosis. It was concluded that the lymphadenopathy in sheep is similar to that in rabbits, mice and man with toxoplasmosis.

Animals↗

Human intestinal mucosal mast cells: evaluation of fixation and staining techniques.

The staining properties of tissue mast cells are influenced by the method of fixation. Differences in fixation and staining techniques may explain the contradictory results in the published reports on the number of human mucosal mast cells (MMC) in the gastrointestinal mucosa in health and disease. We have examined the influence of fixatives on the staining properties of human MMC in operative biopsy specimens of human jejunum. Specimens were divided into pieces, each of which was fixed in one of the following fixatives: Carnoy's, basic lead acetate (BLA), Baker's, Bouin's, isotonic formol-acetic-acid (IFAA), 10% neutral buffered formalin, formol sublimate, and formol saline. Thereafter, tissues were paraffin-embedded and 5 micron sections were cut and stained with either astra-blue/safranin pH 0.3, or toluidine blue pH 0.5. Counts of the number of MMC/mm2 were obtained for each fixation method. The results show a critical influence of the fixative on the number of mast cells identified after staining. For example with astra-blue/safranin the mean MMC/mm2 count was 40 in formol-saline-fixed specimens, and 268 in Carnoy's-fixed specimens. In biopsies fixed with formalin-based fixatives, mast cells were more readily stained with toluidine blue. It is recommended that Carnoy's or BLA be used as the fixative for any light microscopic study of human MMC.

Cell Count↗

Prorating incomplete Wiggins and MacAndrew Scales.

A table is provided for prorating the Wiggins Content Scales and MacAndrew Alcoholism Scale from the Minnesota Multiphasic Personality Inventory (MMPI) when the entire form has not been completed. Conversion factors are given in increments of 10 items for 200 to 400 completed questions. Means, standard deviations, and comparisons of the number of scales over 70 were calculated from 236 profiles, using 200, 250, 300, 350, and 400 items. Results indicate that the conversion factors tend to overestimate scale elevations for the Wiggins scale. The MacAndrew scale can be used for clinical purposes with as few as 200 MMPI items completed, but clinical interpretation of prorated Wiggins scales should be done cautiously.

Journal Article↗

Adoptive transfer of total and parasite-specific IgE responses in rats infected with Nippostrongylus brasiliensis.

Infection of rats with Nippostrongylus brasiliensis has both a parasite-specific and non-specific IgE stimulating effect. Both these responses can be adoptively transferred with thoracic duct lymphocytes (TDL) from infected rats. The character of the IgE response in the recipient rats was related to the stage after infection of the cell donors. TDL from hyperimmune rats adoptively transferred high serum titres of parasite-specific IgE to infected recipient rats and substantially increased the levels of total IgE. However, adoptive immunization with TDL from donors infected 10 days previously did not stimulate parasite-specific IgE and only slightly increased total IgE levels. After cell fractionation the sIg- cells from day 10 TDL increased the level of total IgE but not parasite-specific IgE whereas sIg- cells from hyperimmune TDL did not induce any IgE response unless given with sIg+ cells. The possible reasons for this are discussed.

Animals↗

Immune exclusion and mucus trapping during the rapid expulsion of Nippostrongylus brasiliensis from primed rats.

AThe phenomenon of rapid expulsion (RE) of Nippostrongylus brasiliensis was examined in Wistar rats. Within 4 hr of intraduodenal challenge with 4 day old N. Brasiliensis greater than 85% of the worms were expelled from rats immunized by infection 18 days previously with 4000-6000 third stage larvae. Rapid expulsion was unaffected by the challenge dose but waned with time after primary infection. Histological observations suggested that the parasites were excluded from their predilection site between the villi in immune rats and that they were separated from the mucosa by a superficial layer of mucus. A newly developed intestinal wash-out technique demonstrated that the 70%-80% of worms in previously uninfected controls were adherent to the mucosa whereas in immune rats 28%-36% of the parasites were adherent and 3%-23% were trapped in mucus. These experiments establish that immune exclusion and mucus trapping are early events in the expulsion process. The possible mechanisms controlling these phenomena are discussed.

Animals↗

Expulsion of Nippostrongylus brasiliensis from rats protected with serum. I. The efficacy of sera from singly and multiply infected donors related to time of administration and volume of serum injected.

Several of the parameters related to the efficacy of passive protection against Nippostrongylus brasiliensis were studied in female hybrid (PVG/c x DA)F1 and outbred Wistar rats. The time after infection at which immune serum was given did, to some extent, alter the degree of protection conferred. There was substantial protection 8 days after challenge in rats given hyperimmune serum (HIS) either as daily injections 4-7 days post-infection or as a single dose on day 4. Eight separate experiments in which HIS was injected 4 days after challenge with 1000 l3 resulted in expulsion of 96 +/- 2% of the worm burdens by day 8. In a further six experiments, following infection with 2000 l3 and using the same protocol, 85 +/- 3% of the worm burden was expelled by day 8. A lag of 2 days between serum transfer and commencement of worm expulsion was consistently observed and, within the space of a further 2-4 days, more than 95% of the parasites were expelled. Transplanted 'normal' and 'damaged' adult worms were also susceptible to the passive transfer of HIS. Sera recovered from rats immunized with two or three challenges (hyperimmune sera) were more protective than sera from rats given one challenge. Serum from rats challenged for the first time 6 days previously conferred significant protection against a 1000 l3 infection and sera recovered 8 and 10-12 days post-infection with 4000 l3 protected recipients with increasing effectiveness. Thoracic duct lymph collected on the tenth day of infection with 4000 l3 was also protective. The response to both primary infection and hyperimmune serum was dose-dependent. The consistently good protection achieved in the present study when compared with the variable success of previous experiments (reviewed by Ogilvie & Jones, 1971) may be a function of the strain and sex of the rats used, together with modifications of the immunization protocols. The relevance of these findings to mucosal defences against N. brasiliensis is discussed.

Animals↗

Intestinal goblet cell differentiation in Nippostrongylus-infected rats after transfer of fractionated thoracic duct lymphocytes.

Adoptive immunization of Nippostrongylus-infected rats augmented goblet cell differentiation in the intestinal epithelium. After fractionation of immune thoracic duct lymphocytes (TDL), cells lacking surface immunoglobulin (sIg-) were the most potent stimulators of goblet cell differentiation. Moreover, TDL drained from rats harbouring a primary infection were more effective than TDL from hyperimmune rats.

Animals↗

Immune regulation of intestinal goblet cell differentiation. Specific induction of nonspecific protection against helminths?

Goblet cell differentiation (GCD) was studied in the intestines of rats infected with Nippostrongylus brasiliensis since an important component of the immune expulsion of this parasite is thought to be nonspecific. An increase in the proportion of villous goblet cells occured at the time of worm expulsion during a primary infection. GCD was augmented by the passive transfer of immune thoracic duct lymphocytes and immune serum in infected rats but not in normal controls. Since drug-induced expulsion of the worms did not induce comparable changes, it was concluded that increased GCD in passively immunized rats was not simply a repair phenomenon. Passive protection with serum was abrogated by reserpine and prednisolone and GCD was depressed in the recipients of these drugs. The possibility that goblet cell differentiation and mucus release are part of the nonspecific component of worm expulsion is discussed.

Animals↗