Biomedical subjects

C F Kuper

Publications and source records attributed to C F Kuper.

At least 37 records · Page 2Linked to original sources

PubMed1994

Acute and subacute inhalation toxicity of germanium dioxide in rats.

Two acute (4 hr) and one subacute (4 wk) inhalation toxicity studies on germanium dioxide (purity > or = 99%, mean particle size 1.7-2.6 microns) were conducted in young adult Wistar rats. In the acute studies, exposure of two groups of five rats of each sex to maximum attainable concentrations of either 3.10 g amorphous or 1.42 g hexagonal germanium dioxide/m3 for 4 hr was not lethal. In the subacute study, four groups of five rats of each sex were exposed to 0, 16, 72 and 309 mg hexagonal germanium dioxide/m3 for 6 hr/day, 5 days/wk during 4 wk. Two additional groups of 5 rats per sex, exposed either to 0 or to 309 mg/m3, were kept for a 33-day post-exposure period. At the end of the treatment period, changes were observed only in rats of the high concentration group: these changes were decreased body weight gain (both sexes), decreases in haematocrit (females) and thrombocyte count (both sexes), and increases in neutrophil count (both sexes) and white blood cell count (females). On clinical chemistry evaluation, decreased fasting blood glucose (females), decreased total protein concentration (both sexes), increased plasma alanine aminotransferase and aspartate aminotransferase activities (females), increased plasma urea nitrogen (males) and increased plasma bilirubin level (females) were observed. In addition, urinary volume was elevated, and urine density and pH were lowered in both sexes. Relative weights of kidneys, spleen, heart and lungs were higher than in controls. Microscopic examination revealed effects on renal tubular epithelium. Effects on growth, kidneys, and liver were still present at the end of the 33-day recovery period. It was concluded that the 4-hr LC50 value of amorphous germanium dioxide was greater than 3.10 g/m3 and that of the hexagonal form greater than 1.42 g/m3. The no-adverse-effect-level in the 4-wk study using hexagonal germanium dioxide was 72 mg/m3.

Administration, Inhalation↗

PubMed1994

Recombinant insulin-like growth factor-II inhibits the growth-stimulating effect of growth hormone on the liver of Snell dwarf mice.

The actions and interactions of recombinant insulin-like growth factor-I and -II (IGF-I and IGF-II), alone or in combination with human GH on body growth and the growth of several organs were studied in the Snell dwarf mouse. IGF-I and -II stimulate to a similar extent sulfate incorporation into cartilage, and both IGFs increase body length and weight. IGF-II as well as IGF-I have clear effects on the size of the submandibular salivary glands, kidneys, and spleen. IGF-II, however, did not influence the weight of the lung, in contrast with IGF-I. GH treatment alone resulted in growth of the liver, whereas both IGFs were inactive. Surprisingly, IGF-II and, to a lesser extent, IGF-I inhibited GH-induced growth of the liver. Glycogen storage in the liver was decreased by treatment with IGF-II alone or in combination with GH, as shown by histological examination. It was not affected by GH, IGF-I, or GH plus IGF-I. Also, the size of the centrilobular hepatocytes was decreased by treatment with IGF-II and IGF-II plus GH; GH alone had a hypertrophic effect, whereas IGF-I or GH plus IGF-I had none. In contrast to GH, IGFs did not increase polyploidy. Treatment with IGF-II increased the level of IGFBP-3, as did IGF-I or GH treatment, as shown by Western ligand blotting. The IGFs appeared to have a greater effect on the induction of 38.5-kilodalton IGFBP-3 than GH, suggesting a different role in the regulation of glycosylation. In conclusion, IGF-I and IGF-II as well as GH have a stimulatory effect on general body growth and are effective in the stimulation of serum IGFBP-3, sulfate incorporation into cartilage, as well as the growth of specific organs in Snell dwarf mice. Both IGFs, alone or in combination with GH, show distinct effects on the growth of the liver with respect to several histological parameters, which require further exploration.

Animals↗

PubMed1993

Ultrastructure of free nerve endings in respiratory and squamous epithelium on the rat nasal septum.

The distribution of nerve fibres in the mucosa of the nasal septum of the rat was investigated by means of transmission electron microscopy on transverse and tangential ultrathin sections. Near the basement membrane of respiratory and squamous epithelium, a rather dense network of unmyelinated nerve fibres occurs. Some fibres in the respiratory epithelium ascend between the epithelial cells to reach up to the tight junctions. These fibres appeared in transverse sections to end as hooks or boutons, sometimes with branches. These shapes resemble the free nerve endings that are considered to act as nociceptors. The small intraepithelial fibres, with diameters of about 0.5-1 microns, contain both dense granules and clear vesicles comparable to synaptic vesicles. Substance P was found in dense granules in basal fibres; vasoactive intestinal peptide was absent throughout the epithelium. Acetylcholinesterase activity was observed closely associated with the basal fibres; the apical fibres showed little if any activity. Membrane specializations pointing to an efferent function as well as structures usually associated with mechanoreceptive functions were lacking in both respiratory and squamous epithelium.

Acetylcholinesterase↗

PubMed1993

Epithelium-free area in the thymic cortex of rats.

The histology of epithelium-free areas in the subcapsular region of the thymus was studied in Wistar rats. Lymphocytes in these areas were CD4/CD8 double-positive, TCR alpha/beta positive in low intensity, and in CD5 labeling either negative or positive in low intensity. There was a high proliferative activity as assessed by bromodeoxyuridine incorporation in vivo and detected by immunohistochemistry. Various macrophage types were observed. They were either large and round to slightly dendritic, or small and dendritic. Most large cells were positive for MHC Class II, and labeled by the antimacrophage antibodies ED1 and ED2. A few cells were strongly positive for Sudan black, Oil red O, nonspecific esterase, and acid phosphatase; they resembled the large rounded macrophages in the corticomedullary zone, although their MHC Class II and ED2 staining was more intense. A few cells showed features of tangible body macrophages, as they contained cellular debris. Serial sections showed that epithelium-free areas run from the subcapsular area to deep in the cortex, and often border the medulla. This opens the opportunity for immature lymphocytes to move into the medulla and corticomedullary zone without contacting and potential selection with cortical stromal elements other than macrophages in the epithelium-free areas. In this case, the epithelium-free areas may offer a separate intrathymic pathway for T lymphocytes.

Animals↗

PubMed1992

The role of nasopharyngeal lymphoid tissue.

Nasal-associated lymphoid tissue (NALT), which comprises paired lymphoid organs in the nasopharynx of rodents, is the principal mucosal lymphoid tissue of the respiratory tract. As described in this review, NALT bears certain similarities to the Peyer's patches of the intestine but the two differ remarkably in morphology, lymphoid migration patterns and the binding properties of their high endothelial venules (HEV).

Animals↗

PubMed1992

Correlations between presence of spontaneous lesions of the pituitary (adenohypophysis) and plasma prolactin concentration in aged Wistar rats.

The predictive value of elevated plasma prolactin concentrations for the presence of spontaneous pituitary lesions was studied in 40 male and 38 female Wistar (Cpb:WU) rats, all 30 months old. The pituitaries were examined light microscopically and stained for prolactin using immunohistochemical methods. Plasma prolactin concentrations were measured by radioimmunoassay. Pituitary lesions were classified on the basis of their morphology in hematoxylin and eosin-stained sections as foci of hypertrophic or hyperplastic cells and hemorrhagic, pleomorphic, or spongiocytic adenomas; no carcinomas were found. There were significantly (P = 0.001) more female than male rats with pituitary adenomas (58% females, 33% males) or without any pituitary lesions (21% females, 5% males); however, there were less female (21%) than male rats (63%) with foci of hyperplastic and/or hypertrophic cells but no adenomas in the pituitary (P = 0.001). Elevation of plasma prolactin concentration above the upper 99th percentile value in age-matched rats without lesions was predictive, but not conclusively, of the presence of pituitary hemorrhagic adenomas in both sexes. It was, however, not predictive of the presence of foci of hypertrophic or hyperplastic cells. Elevation of plasma prolactin concentration above 10 ng/ml in male and 60 ng/ml in female rats was conclusive for the presence of hemorrhagic adenomas. Using multivariate analysis, significant positive correlations (P less than 0.01) were found between plasma prolactin concentration and presence and size of hemorrhagic adenomas and their prolactin staining intensity (correlation coefficients between 0.392 and 0.652). Foci of hyperplastic cells stained positively for prolactin, whereas hypertrophic cell foci and pleomorphic and spongiocytic adenomas did not stain for prolactin. There were no correlations (coefficients of less than +/- 0.189) between plasma prolactin concentration and the presence of hypertrophic or hyperplastic cell foci and pleomorphic or spongiocytic adenomas in the pituitary. The morphologic criteria developed to distinguish spontaneous hypertrophic, hyperplastic, and neoplastic lesions of the rat pituitary corresponded well with their prolactin immunoreactivity and/or ability to elevate plasma prolactin concentration. These criteria constitute a biologically meaningful classification system for these rat pituitary lesions.

Adenoma↗

PubMed1991

Chronic inhalation toxicity and carcinogenicity study of methyl bromide in Wistar rats.

The toxicity and carcinogenicity of methyl bromide (MeBr) were studied in male and female Wistar rats exposed by inhalation to 0, 3, 30 or 90 ppm MeBr 6hr/day, 5 days/wk for 29 months. After 13, 52 and 104 wk ten rats/sex/group were killed to provide interim information. Body weights, clinical signs, haematology, biochemistry and gross and microscopic pathology were studied. Mortality was increased by wk 114 in the 90-ppm group. Body weights in males and females of the 90-ppm group were lower than those of the controls throughout the study. Increased incidences of degenerative and hyperplastic changes of the nasal olfactory epithelium were observed in all exposed groups, the incidences being positively correlated with the MeBr concentration; the nasal lesions did not progress appreciably with time. Exposure to 90 ppm MeBr was associated with an increased incidence of lesions in the heart (thrombi, myocardial degeneration), and with hyperkeratosis in the oesophagus and forestomach. Data on site, type and incidence of tumours in the various groups did not indicate carcinogenic activity of MeBr.

Administration, Inhalation↗

PubMed1990

Interactive effects of dietary wheat bran and lard on N-methyl-N'-nitro-N-nitrosoguanidine-induced colon carcinogenesis in rats.

A 3 x 3 factorial experiment was conducted to examine how dietary fiber (wheat bran) and fat (lard) interactively affect the genesis of N-methyl-N'-nitro-N-nitrosoguanidine-induced colon cancer in rats. Groups of 30 male 4-week-old Wistar rats were fed ad libitum one of nine experimental diets containing either 15 (low), 27.5 (medium), or 40% (high) energy as fat in combination with 0.7 (low), 2.2 (medium), or 3.8 g (high) fiber/100 kcal for a period of 37 weeks. After 4 weeks, each rat received a total of five weekly intrarectal instillations of 6 mg N-methyl-N'-nitro-N-nitrosoguanidine/kg. The highest colon carcinoma incidence and the highest total number of carcinomas of the colon were observed in the animals fed the medium-fat/medium-fiber diet. The highest number of polyps and a relatively high polyp incidence occurred in the animals on the high-fat/low-fiber diet. An enhancing effect of fat on both the tumor incidence and tumor multiplicity was clearly present for the low-fiber diets, whereas fat had no effect when the fiber content of the diet was high. In general, the results showed a nonlinear dose-response relationship for fiber and fat. These results indicate that both dietary fiber and fat affect colon carcinogenesis in a complex, interactive manner.

Adenocarcinoma↗

PubMed1990

Lymphoid and non-lymphoid cells in nasal-associated lymphoid tissue (NALT) in the rat. An immuno- and enzyme-histochemical study.

Lymphocyte and macrophage subpopulations and the stroma of mucosa-associated lymphoid tissue in the nasal cavity of the rat were examined by application of immunohistochemical and enzyme histochemical methods to cryostat sections. Nasal-associated lymphoid tissue was composed of a loose reticular network with lymphocytes and macrophages, covered by epithelium. The epithelium was infiltrated with B cells. T helper (W3/13-positive) and T suppressor/cytotoxic or large granular cells (OX8-positive), ED1-positive macrophages and Ia-positive cells. The B cell areas were populated by B cells, immunopositive for surface IgM or IgG. B cells with surface IgA or IgE were rare. Germinal centres were found infrequently. T helper cells were scattered throughout the B cell area. A few ED1-positive macrophages and ED5-positive follicular dendritic cells were observed. Strong Ia staining (mostly of B cells) was found in this area. The T cell areas contained T helper and T suppressor/cytotoxic cells in about equal amounts, and numerous ED1-positive macrophages. ED1 staining was also found in the subepithelial area. Numerous ED1-, ED2- and ED3-positive macrophages were found in the border between the lymphoid mass and the surrounding connective tissue. A few non-lymphoid cells showed weak acid phosphatase or non-specific esterase activity. The morphological observations suggest that nasal-associated lymphoid tissue plays an important role in the first contact with inhaled antigens.

Animals↗

PubMed1989

Macroscopic and microscopic early effects of tumour necrosis factor on murine Meth A sarcoma, and relation to curative activity.

Mice with solid Meth A sarcoma in the skin received an intravenous or intralesional injection of graded doses of recombinant human tumour necrosis factor (rTNF). Local treatment caused red discolouration and necrosis of the central portion of the tumour within 24 h over a larger range of doses than intravenous treatment. Effects showed a limited dose dependence and no significant correlation with subsequent cures, which were far more frequent after local treatment. A dose of rTNF that induced about equal macroscopic necrosis by both routes caused much more pronounced microscopic effects after local administration. Effects included mitotic arrest, granulocyte margination, endothelial damage, hyperaemia, congestion, oedema, and tumour cell necrosis. rTNF did not affect the Meth A cells in vitro. Locally injected skins showed moderate vascular effects which were more marked in tumour-bearing mice, but skin necrosis was absent. Data show that quantitative histology rather than macroscopically visible necrosis correlates with cure rates. A broad interference of rTNF with tumour blood supply seems to be a major cause of the induced necrosis. Granulocytes may be involved in vascular damage. The different effects of rTNF on skin and tumour indicate that tumour vasculature has enhanced susceptibility to rTNF and probably lesser repair capacity.

Animals↗

PubMed1989

Nasal lymphoid tissue in the rat.

The structure and organization of paired lymphoid tissue in the nasal mucosa, situated in the transitional zone on both sides of the septal opening of the pharyngeal duct, of conventionally-housed rats was examined by light microscopy and scanning and transmission electron microscopy. Each lymphoid structure consisted of follicles containing T- and B-cell areas, and was covered with specialized epithelium. This epithelium consisted of cuboidal ciliated cells with oval nuclei parallel to the basal lamina. Goblet cells were sparse. Occasionally, islands of microvilli-bearing cells (so called membraneous or M cells) covered the lymphoid structures. M Cells were also found as single cells among the ciliated cells. The morphological characteristics and the particular localization justify the conclusion that the nasal lymphoid tissue described belongs to the mucosa-associated lymphoid tissue. It is therefore suggested that this nasal structure be designated nasal lymphoid tissue.

Animals↗

PubMed1988

Comparative sensitivity of histo-pathology and specific lung parameters in the detection of lung injury.

The sensitivity of different parameters for the determination of lung injury caused by nitrogen dioxide (NO2) was investigated. Male rats were exposed to concentrations of 0, 4, 10 or 25 ppm NO2 for 6 h/day, for 7, 14 or 21 days. Histopathology of the nasal cavity, larynx, trachea and lungs was compared with the changes in macrophage function and morphology. In addition several biochemical parameters were determined in lung lavages. Cytotoxic effects were investigated in primary cultures of rat and bovine alveolar macrophages, exposed to the same NO2-levels as in the in vivo exposure. Treatment-related histopathological changes were observed in the lungs. No differences between exposed and control animals were observed in the nasal cavity, larynx or trachea. The morphology of the lavaged alveolar macrophages was changed at all exposure concentrations on day 7, 14 and 21. An increase in the number of macrophages was found after exposure to 10 and 25 ppm NO2 on days 7, 14 and 21. The phagocytic capacity was diminished after 14 and 21 days exposure to 25 ppm and at both times exposure to 10 and 25 ppm increased the level of gamma-glutamyl transferase (GGT) in lavage fluids. Morphology of the macrophages and levels of GGT were found to be sensitive parameters of nitrogen dioxide toxicity. In vitro exposure of rat and bovine alveolar macrophages to comparable NO2-concentrations induced effects on phagocytosis similar to those observed for macrophages from exposed rats.

Administration, Inhalation↗

PubMed1988

Antitumor effects of endotoxin against solid murine Meth A tumors of different ages. Quantitative histology of the tumors and regional lymph nodes.

Mice with 3-, 6-, 9- and 15-day Meth A tumors in the skin were injected intravenously with endotoxin to study age-dependent induction of tumor necrosis and reactive changes in draining lymph nodes. By 24 h after treatment with endotoxin, macroscopic necrosis was seen in 9-day, and to an even greater extent in 15-day tumors; microscopy showed extensive necrosis in 9-day tumors and some necrosis in 6-day tumors. The necrosis was predominantly coagulative, but the 9- and 15-day tumors showed a rim of hemorrhagic necrosis near the skin with surviving tumor tissue located at the lateral and basal margins. All the tumors showed about equal hyperemia by 4 h and mitotic arrest by 4 and 24 h. Depletion of mast cells, which were most numerous in the 9-day tumors, was seen on the dermal aspects by 24 h. Endotoxin did not change the morphology of the lymph nodes and disseminated tumor cells within 24 h. Endotoxin is known to cure 9-day Meth A tumors, and the extent of the rapid necrosis induced is clearly the crucial factor. Necrosis, however, is not a direct consequence of early hyperemia or mitotic arrest and other factors related to the age and site of the tumor, apparently affect whether or not necrosis ensues.

Animals↗

PubMed1988

Evaluation of the oral toxicity of potassium nitrite in a 13-week drinking-water study in rats.

A subchronic oral toxicity study with potassium nitrite (KNO2) was carried out in rats. Groups of ten male and ten female 6-wk-old rats received KNO2 in the drinking-water (tap-water) at levels of 0, 100, 300, 1000 and 3000 mg/litre for a period of 13 wk. The potassium concentration in the nitrite solutions was equalized by adding potassium chloride (KCl) up to the potassium level of the 3000-mg KNO2/litre solution. An additional group of ten males and ten females received drinking-water supplemented with KCl only, at an amount resulting in a potassium concentration equivalent to that of the 3000-mg KNO2/litre solution. Body weight, food intake and food efficiency were decreased at 3000-mg/litre level in males, while liquid intake was decreased in males given 1000 and 3000 mg/litre and in females given 3000 mg/litre. There was significant increase in the methaemoglobin concentration in animals given 3000 mg/litre, while slight decreases in red blood cell variables occurred at the 1000- and 3000-mg/litre dose. No impaired renal function was observed in any of the test groups, although the relative weight of the kidneys and the plasma urea nitrogen level was increased at 3000 mg/litre. There was a slight decrease in plasma alkaline phosphatase activity at 3000 mg/litre. A small amount of nitrite was present in the saliva of the rats receiving 3000 mg/litre but there was no evidence of increased mutagenic activity in the urine of these rats. Interestingly, hypertrophy of the adrenal zone glomerulosa was observed in all test groups, the incidence and degree being dose related. It was concluded that in the study reported here the no-effect level is lower than 100 mg KNO2/litre in the drinking-water, which is equivalent to a level lower than 10 mg KNO2/kg body weight/day.

Administration, Oral↗

PubMed1988

Chronic inhalation toxicity and carcinogenicity study of propylene oxide in Wistar rats.

Four groups of 100 Wistar rats of each sex were exposed by inhalation to 0, 30, 100 or 300 ppm propylene oxide for 6 hr/day, 5 days/wk for 28 months. After 12, 18 and 24 months ten rats/sex/group were killed to provide interim haematological, biochemical and urinary data. Mortality was increased by wk 115 in both sexes in the 300-ppm group and by wk 119 in females of the 100-ppm group. Body weights were lower than those of the controls throughout the study in males of the 300-ppm group and in females of the 300-ppm group during the first year of the study. Increased incidences of degenerative and hyperplastic changes of the nasal mucosa were observed in all exposed groups. Exposure to 300 ppm propylene oxide was associated with an increased incidence of both benign and malignant mammary tumours in females. There was no increase in the incidence of any particular type of tumour other than mammary tumours. The total number of rats bearing malignant tumours at sites other than the mammary glands was increased in both sexes in the 300-ppm group compared with the controls.

Administration, Inhalation↗

PubMed1988

The role of macrophages in LPS-induced lethality and tissue injury.

In the present study we investigated the role of mononuclear phagocytes in the pathogenesis of lipopolysaccharide (LPS)-induced lethality and tissue injury. Since hepatic and splenic macrophages are the primary sites of localization of i.v.-injected LPS, we selectively eliminated these macrophages using liposome-encapsulated dichloromethylene diphosphonate (DMDP). After double DMDP-liposome treatment the phagocytic cells in the liver and spleen were completely eliminated, except for the macrophages in the white pulp of the spleen which were affected to a lesser extent by this treatment. An i.v. injection of LPS into DMDP- and saline-pretreated mice showed that the latter animals exhibited febrile-associated symptoms such as lethargy and ruffled fur, but that macrophage elimination abrogated these symptoms. Although after double saline- or DMDP-pretreatment the LD50 appears to be 1 mg and 630 micrograms, respectively, the differences in lethality between both groups of mice were not statistically significant. Therefore, we concluded that hepatic and splenic macrophages are not necessary for LPS-induced lethality. The role of macrophages in LPS-induced local tissue damage was studied by comparing the histopathological changes in hepatic and splenic tissue between DMDP- and saline-pretreated mice. A sublethal dose of LPS induced similar hepatic lesions in macrophage-depleted and saline-pretreated mice, whereas the histopathological changes in the spleen were much more pronounced after DMDP-pretreatment. Particularly in the inner periarteriolar lymphocyte sheath (PALS) of these mice, the number of T cells was considerably reduced and extensive cellular necrosis could be found. These data strongly suggest that the local tissue damage resulting from LPS injection may not be due to its localization in mononuclear phagocytes but rather to interaction with other cell types.

Animals↗

PubMed1987

Quantitative histology of muramyl dipeptide-potentiated induction of tumor necrosis by endotoxins.

Combinations of muramyl dipeptide (MDP) and toxic or detoxified endotoxin induced necrosis and subsequent disappearance of solid Meth A tumors in syngeneic mice. Toxic endotoxin alone was far less effective. MDP and detoxified endotoxin had negligible antitumor effects of their own. These observations were confirmed by histological examination. Neither MDP nor detoxified endotoxin induced significant changes in and around the tumor by 4, 24, and 48 h after intravenous administration when compared with saline treatment. MDP amplified various effects of toxic endotoxin such as the induction of hyperemia, mitotic arrest, mast cell depletion, non-hemorrhagic necrosis and reduction in lymphocyte infiltrates, but did not affect hemorrhagic necrosis or the influx of polymorphonuclear leukocytes. The combination of MDP and detoxified endotoxin lacked the latter two effects, but the other effects were similar to, although slightly less marked than those induced by the toxic combination. Because the degree of hyperemia was proportional to the degree of subsequent non-hemorrhagic necrosis, MDP seems to potentiate necrosis by enhancing mechanisms leading to hyperemia and mast cell mediators might be involved in the latter effect. Lymphocyte influx and the therapeutic outcome are likely to be related, since exclusively therapeutic treatments reduced the influx of these cells.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1986

In vivo effects of toxic and detoxified endotoxin alone or in combination with muramyl dipeptide on lymphoid and non-lymphoid cells in the spleen of Meth A sarcoma-bearing mice.

In this study we confirmed that combinations of toxic or detoxified endotoxin with muramyl dipeptide (MDP) induced much more necrosis of transplanted Meth A sarcoma in mice than toxic endotoxin alone. Detoxified endotoxin and MDP alone had little antitumor effects. We investigated whether these divergent antitumor effects could be related to histopathological changes in the white pulp of the spleen of Meth A sarcoma-bearing mice. Toxic endotoxin reduced the T:B cell compartment ratio in the splenic white pulp by increasing the size of the B-cell compartment while leaving the size of the T-cell dependent inner PALS unaffected. The number of the T-lymphocytes in this area, however, was reduced. The border of B-lymphocytes in the marginal zone was markedly narrowed and the number of marginal metallophils along the inner border of the marginal sinus was decreased. None of these changes were observed after treatment with detoxified endotoxin or MDP. Addition of MDP to either endotoxin did not change their effects. The histopathological changes in the lymphoid and non-lymphoid compartments of the splenic white pulp are apparently exclusively induced by toxic endotoxin. As the antitumor activity of both toxic and detoxified endotoxin combined with MDP are about equal and more powerful than the activity of toxic endotoxin alone, it is concluded that these antitumor effects cannot be related to changes in the white pulp of the spleen.

Acetylmuramyl-Alanyl-Isoglutamine↗