Severe Inflammatory Lesions Research Articles

Changes in neuropeptide-containing nerves in human colonic mucosa with inflammatory bowel disease.

The distribution abnormality of vasoactive intestinal polypeptide-containing nerves (VIP-nerves) and substance P-containing nerves (SP-nerves) was immunohistochemically investigated in the colonic mucosa with inflammatory bowel disease (IBD) in relation to colonic glands and blood vessels in the lamina propria. In active ulcerative colitis (UC), VIP- and SP-nerves decreased in severe inflammatory lesions. VIP-nerves were almost absent particularly around crypt abscesses. Even in resolving and quiescent UC, VIP-nerves still decreased, depending on the decrease of glands and blood vessels. On the other hand, both nerves increased in some hypervascular lesions. In the uninvolved mucosa of UC, they did not change their distribution. In Crohn's disease, the distribution abnormality of both nerves resembled that of UC. These results suggest that the changes in VIP- and SP-nerve distributions in the mucosa with IBD are subsequent to mucosal inflammation and damage. However, these peptides are known to be immunoregulators, and their distribution abnormalities may induce the disorder of immunoregulation in the IBD mucosa and cause the mucosal damage and/or chronicity.

Promoting and synergistic effects of chrysazin on 1,2-dimethylhydrazine-induced carcinogenesis in male ICR/CD-1 mice.

The modifying effects of chrysazin on 1,2-dimethylhydrazine (DMH)-induced colon and liver carcinogenesis were examined in male ICR/CD-1 mice. Starting at 6 weeks of age, mice were divided into four groups, two of which were treated with s.c. injections of DMH (20 mg/kg body wt) once a week for 12 weeks. A week after the final injection of DMH, one group was kept on the basal diet throughout the study (group I), and the other group was fed the diet containing chrysazin (mixed in basal diet at 0.2% concentration) alone for 42 weeks (group II). The other two groups were injected with normal saline and given the diet containing 0.2% chrysazin for 42 weeks (group III), or the basal diet during the experiment (group IV). The incidence and multiplicity of colon tumors of group II were significantly greater than those of group I (P < 0.05, P < 0.01). The incidence and multiplicity of the hepatocellular neoplasms of group II were larger than those of group I (P < 0.002, P < 0.02 respectively). In group III, colon tumors were not found, though a few liver neoplasms and severe inflammatory lesions of the colon were observed. The activity of ornithine decarboxylase of the colonic mucosa in mice exposed to chrysazin was stronger than that of animals without chrysazin. The results suggest that the promoting effect of chrysazin is probably related to an increase of cell proliferation in the target organ. A synergistic effect of DMH with chrysazin was also observed in liver tumorigenesis.

Evaluation of a new synthetic antimicrobacterial agent, OPC-7251 cream in the treatment of acne vulgaris with moderate or severe inflammatory acne lesions: A multicenter, double-blind, gruop comparative study with a cream base

Evaluation of a new synthetic antimicrobacterial agent, OPC-7251 cream in the treatment of acne vulgaris with moderate or severe inflammatory acne lesions: A multicenter, double-blind, gruop comparative study with a cream base

Factors affecting the distribution of ingested propionic acid in the rat forestomach

Propionic acid (PA) when incorporated into food pellets and fed to male Wistar rats for 20 wk had no effect on the forestomach mucosa; however, in powdered diet PA led to pronounced hyperplasia and severe inflammatory lesions in the forestomach mucosa near the limiting ridge. Since this discrepancy in the effect of PA may have been caused by the type of diet in which PA was administered, the distribution of total PA (including the corresponding acid-soluble CoA ester) in different parts of the stomach and certain variables affecting this distribution were investigated. In the forestomachs of rats fed 4% PA in powdered diet, the amount of PA in hyperplasias (1553 ± 508 μg PA/g tissue) was three times higher than that in the remainder of the tissue (479 ± 247 μg PA/g tissue). The PA content decreased progressively towards the glandular parts. There was a slight, but not significant, decrease in the PA content of the forestomach and a slight increase in the PA content of the glandular stomach in rats fed pelleted food compared with those fed powdered diet. Supplementation of 1% l-carnitine to PA powdered diet for 12 wk led to a significant decrease ( P < 0.02) in PA accumulation in hyperplastic tissues compared with hyperplasias induced by PA alone, although l-carnitine had no influence on the severity of hyperplastic changes in the forestomachs of rats. The present study shows that the type of diet in which PA was administered to male Wistar rats is of great importance for the development of hyperplasia, PA or the corresponding CoA ester can accumulate in the forestomach and is preferably accumulated in hyperplasias, and PA accumulation does not appear to be directly related to the severity of hyperplastic changes.

Interstitial Inflammatory and Chronic Tubulointerstitial Lesions in Lupus Nephritis: Comparison with those in IgA Nephropathy

The significance of interstitial inflammatory and chronic tubulointerstitial lesions was studied in relation to the severity of glomerular lesions in 62 patients with lupus nephritis and 88 with IgA nephropathy. Severe interstitial inflammatory and chronic tubulointerstitial lesions were found in patients with severe glomerular lesions in both lupus nephritis and IgA nephropathy. In such cases, the serum creatinine levels at biopsy were high and the renal prognosis was poor regardless of the underlying disease (lupus nephritis or IgA nephropathy). No IgA nephropathy patients with nil or mild glomerular lesions had moderate or severe interstitial inflammatory and/or chronic tubulointerstitial lesions. In contrast, predominantly severe interstitial inflammatory lesions were found in 36% of lupus nephritis patients with nil or mild glomerular lesions. The prevalence of interstitial immune complexes deposition was markedly high in those with predominant interstitial inflammatory lesions. However, the severity of chronic tubulointerstitial lesions was mild and renal function did not deteriorate in the mean follow-up periods of 68.6 months. It is suggested that, besides the tubulointerstitial lesions attributable to the severe concomitant glomerular damage, the interstitial deposition of immune complexes per se plays a pathogenic role in the interstitial inflammatory lesions in lupus nephritis. Its prognostic significance, however, was considered to be minor.

Calcitonin secretion in a primary culture of isolated ultimobranchial bodies of rat fetuses

We immunohistochemically investigated the distribution of vasoactive intestinal peptide (VIP)-immunoreactive nerve fibers (VIP-nerves), in the colonic mucosa with and without ulcerative colitis (UC), and analyzed the relationship with other structural components, such as colonic glands and capillaries. In the control, VIP-nerves were distributed along by colonic glands or by capillaries, or without relation to glands and capillaries in the lamina propria. In the severe inflammatory lesions of active UC, VIP-nerves decreased, particularly around crypt abcess. In active and revolving UC, however, increased supply of VIP-nerves was observed in the hypervascular areas

Expression of adhesion molecules and histocompatibility antigens at the blood-brain barrier.

The migration of inflammatory cells through the blood-brain barrier in health and disease involves complex interactions between hematogenous cells, endothelial cells, the basement membrane and the perivascular glia limitans. Recent evidence is presented, suggesting that part of these interactions involve antigen independent mechanisms, mediated by cellular adhesion molecules. The accessibility of endothelial adhesion molecules in the intact blood-brain barrier is lower compared to vessels in other organs. This may account for the low traffic of hematogenous cells through the normal blood-brain barrier. However, in inflammatory conditions the expression of endothelial adhesion molecules is upregulated, which may lead to recruitment of inflammatory cells into the lesions. Antigen specific activation of T-cells at the blood-brain barrier apparently takes place mainly at perivascular monocytes and microglia cells. In severe inflammatory lesions, however, astrocytes may be additionally involved in antigen presentation.

Periapical reactions to calcium hydroxide‐containing sealers and AH 26® in monkeys

The long-term effect on periapical healing (8-14 months) of CRCS and Sealapex was compared with that of AH 26. Vital pulpectomy and root canal filling by the hybrid thermomechanical method were performed in teeth of 3 young monkeys. Ten roots with CRCS, 10 with Sealapex and 7 roots with AH 26 were examined after demineralization and routine histological processing. Hematoxylin and eosin and Brown & Brenn staining for micro-organisms were employed. Mild to severe inflammatory lesions were found at the apical foramina of the roots filled with AH 26 and CRCS. Most of the Sealapex specimens showed no inflammatory cells, except macrophages with sealer particles. A striking finding was a tendency towards apical obliteration with calcified tissue in roots filled with Sealapex, apparently following resorption of the sealer. Such a tendency was seldom observed with the other sealers. However, both AH 26 and Sealapex were irritating for a long time when pushed into bone. Despite the interesting results with Sealapex, additional research is needed before its use can be unconditionally recommended. This sealer has not yet been tested in infected cases and its ability to be resorbed, which is an advantage when it precedes replacement by calcified tissue, may become a disadvantage if it is not followed by apical obliteration.

Direct Activation of Human Polymorphonuclear Leukocytes by &lt;i&gt;Pseudomonas aeruginosa&lt;/i&gt;

Brief exposure of polymorphonuclear leukocytes (PMNs) to unopsonized Pseudomonas aeruginosa resulted in significant enhancement of PMN adherence and 3H-deoxyglucose uptake, two important indicators of PMN activation. Dose-response and time-course experiments show that maximal stimulation of PMNs occurred at a PMN: bacteria ratio of 10:1 and exposure time of 10 min. The PMN-stimulatory capacity of P. aeruginosa was completely or partially abolished by treatment with formalin, heat, ultrasonication and ultraviolet (UV) irradiation, all of which affect the integrity of ligands on the bacteria surface. The putative glycoprotein ligand(s) contains galactose rather than glucose as shown by the ability of galactose in the medium to abrogate PMN-stimulatory activity. This PMN-stimulatory activity was not mediated by soluble factor(s) released from either P. aeruginosa or PMNs as shown by experiments with appropriate supernatants. Finally, PMN-stimulating activity was also observed with P. maltophilia and P. pseudomallei, but not by the other Pseudomonas spp. such as P. cepacia and P. fluorescens. These results suggest that P. aeruginosa and other Pseudomonas spp. may have little capacity to circumvent PMN host defences. This may account in part for their limited pathogenic role as opportunistic micro-organisms, for the severe inflammatory lesions seen in Pseudomonas infections when they do occur, and is consistent with the fact that infection with these organisms is commonly associated with impaired quantity or function of PMNs.

Histopathology of arthritis induced in rats by active immunization to mycobacterial antigens or by systemic transfer of t lymphocyte lines. a light and electron microscopic study of the articular surface using cationized ferritin

We analyzed the histopathologic findings of arthritis in 3 rat models: adjuvant arthritis induced by active immunization to Mycobacterium tuberculosis (MT) antigens, arthritis produced by passive transfer of an intrinsically arthritogenic line of anti-MT T lymphocytes, and bystander arthritis produced by intraarticular injection of a foreign antigen, ovalbumin, into rats with T lymphocyte line cells specific for the ovalbumin antigen. The histopathology of the tibiotarsal and knee joints was studied by light microscopy and the articular surface of the cartilage by electron microscopy after labeling with cationized ferritin. The lesions in the 3 models of arthritis were compared. In active adjuvant arthritis, inflammatory lesions and cartilage destruction were found as early as 9 days after immunization, and persisted for as long as 11 months. Similar, but somewhat milder, lesions were found in arthritis produced by transfer of anti-MT T lymphocytes. Inflammatory signs were present at 4 days, when there was no evidence of joint edema. Severe inflammatory lesions were found in arthritis induced by transfer of anti-ovalbumin T lymphocytes that was followed by ovalbumin injection into the knee. Pathologic changes were found to be similar in all 3 models. Thus, the changes could be attributed to the action of T lymphocytes, irrespective of whether the target antigen was intrinsic to the joint.

The function of the primordial germ cell in extragonadal tissues.

The identity of the germ cell tumours of the pineal and the thymus with those of the testis and ovary suggests that the widely disseminated primordial germ cells might subserve some special function in these sanctuaries. It is proposed that thymic localization might be required for the conveyance of genetic haematological and immunological information and that the pineal-diencephalic localization could programme neuroophthalmic tissues prior to the development of the blood-brain barrier. The latter speculation was tested by producing allergic encephalomyelitis in thymectomized, bursectomized and thymobursectomized chickens. It was found that although thymectomy and, to a lesser extent, bursectomy decreased the severity of the experimental encephalomyelitis the combined procedure resulted in more severe inflammatory lesions. This may be due to release of suppressed intraneural immunological mechanisms in the somatically impaired bird.

Healing capacity of human and monkey dental pulps following experimentally‐induced pulpitis

Abstract Intra‐ and extracellular products from oral bacteria were placed in Class V cavities prepared in dentin of human and monkey teeth to compare initial and late pulp tissue reactions. In one set of teeth, the bacterial material was left in the cavities for the entire experimental period (4, 10, 30 d in monkeys, 30 d in humans). In other teeth the challenge was stopped after 32 h and the bacterial material was removed and substituted with zinc‐oxide eugenol cement. The subsequent pulp tissue responses were observed histologically after 4, 10 (monkeys) and 30 d (humans and monkeys). Thirty‐two hours of bacterial challenge to human teeth induced intense acute inflammatory lesions. Four days of challenge in monkeys resulted in severe inflammatory cell involvement and pulpal necroses in a few teeth. At extended periods of observation severe inflammatory lesions were less frequent and the majority of the pulps showed tissue repair and healing at 30 d. This occurred irrespective of experimental protocol. Fourteen of 84 monkey teeth and none of 17 human teeth presented pulp tissue necrosis at follow‐up. Data showed that the‐dental pulp of both young human and monkey teeth can recuperate from a state of suppurative inflammatory involvement. Healing occurred irrespective of whether the bacterial challenge was removed or left in place. Findings also indicated that an acute inflammatory lesion rapidly could result in total pulp tissue necrosis.

Antibody Responses in Sera and Respiratory Secretions from Chickens Infected with Mycoplasma gallisepticum

Antibodies in sera and respiratory secretions from chickens infected with Mycoplasma gallisepticum (MG) were measured by an enzyme-linked immunosorbent assay (ELISA). Chickens intratracheally inoculated with 10(5) cells of MG showed a correlation between severity of tracheal lesions and extent of MG colonization in the tracheas in the first 3 weeks postinoculation. Antibody titers in tracheal washings (TWs) of the infected chickens increased during this phase. Thereafter, isolation of MG from the trachea decreased sharply, and there was a concomitant decrease in tracheal lesion scores. At 5 weeks postinfection, the chickens that recovered from the infection exhibited a consistent presence of antibodies in TWs. Chickens reexposed had a faster rate of MG elimination and substantially less severe inflammatory lesions in the tracheas than chickens observed after the first exposure. These findings suggest a possible role of antibodies of the respiratory secretions in resistance to MG. The ELISA was a sensitive and reliable test to detect a minute amount of antibodies in the secretions.

Hind-limb motor ability in Lewis rats during the onset and recovery phases of experimental autoimmune encephalomyelitis

Hind-limb motor function in adult female Lewis rats with experimental autoimmune encephalomyelitis (EAE) was investigated using an objective behavioral measurement of motor ability. Rats were pretrained to avoid falling from the external surface of a power-driven running wheel. The performance of EAE-group rats on the wheel was then compared with that of saline and adjuvant controls immediately prior to the onset of clinical signs of EAE, and within 3 days of apparent recovery from EAE. Results indicate no apparent hind-limb motor dificit in the absence of overt clinical signs of EAE, despite histological evidence of severe inflammatory lesions persisting in the central nervous system (CNS) at the time of the post-recovery test. The remarkably transient nature of motor impairment is discussed within the context of a continuing search for the underlying cause(s) of clinical signs of EAE.

Isolation and preliminary characterization of Semliki Forest virus mutants with altered virulence.

Four mutants of Semliki Forest virus (SFV) strain Lio showing altered virulence in weanling mice were selected following mutagenesis with N-nitro-N-methyl-N'-nitrosoguanidine. Intraperitoneal (i.p.) injection of wild-type (wt) virus resulted in the death of all mice given more than 30 p.f.u. Protection of mice surviving injection with lower doses of virus was not obtained. A proportion of mice infected with doses from 10(4) to 10(7) p.f.u. of mutant virus survived infection. Such surviving mice were protected against an otherwise lethal challenge with wt virus. Three mutants which were non-lethal at loses of 10(2) p.f.u. were studied further. The mutants M4 and M103 established a transient viraemia which was quickly cleared; unlike the wild-type, the virus did not enter the brain or spinal cord. The mutant M136 produced a viraemia similar to the wild-type, but reached a lower titre in the brain; it was not recovered from the spinal cord. Severe necrotic and inflammatory lesions, associated with large numbers of virus particles, were present in the brain and spinal cord (CNS) of mice 5 days p.i. with wt virus. Mice infected with M136 showed degenerative lesions in the grey and white matter of the CNS at 13 days p.i. Virus particles could not be detected at this time either by electron microscopy or infectivity assays.

The pathomorphology of malignant catarrhal fever. II. Multisystemic epithelial lesions.

Epithelia from 18 Holstein-Fresian calves with experimentally induced malignant catarrhal fever and two calves with naturally occurring disease had severe destructive inflammatory epithelial lesions. Calves were necropsied at early, mid and late clinical stages. Multifocal, degenerative and necrotic epithelial lesions were associated with lymphoid cells. Ultrastructurally, numerous lymphocytes, lymphoblasts and macrophages were accumulated between epithelial cells and in lamina propria, vessels and perivascular tissues. Epithelial cells in such lesions had variably severe degenerative changes or were necrotic but there was no proliferative response. Lesions were widespread in all calves and affected oral, ocular, gastrointestinal, ductal, urinary tract, choroid plexus and other epithelial tissues. Calves killed in late clinical stages had more severe lesions than those killed early. The predominantly lymphocytic, invasive-destructive pattern seen in tissues of cattle with malignant catarrhal fever was similar to that seen in such conditions as contact hypersensitivity and graft versus host disease. Viral structures were not seen.

Inflammatory lesions and bone resorption induced in the rat periodontium by lipoteichoic acid of Streptococcus mutans.

Severe inflammatory lesions were induced in the periodontal tissues of the rat following the intragingival injection of lipoteichoic acid (LTA) from Streptococcus mutans. There was no difference in the severity and distribution of the lesions between nonimmunized rats and animals immunized against LTA after antigenic challenge. The lesions are characterized by the occurrence of granulation tissue, massive infiltration of PMNs, abscess formation, bone resorption, and new bone formation. Deacylated LTA and saline caused relatively mild inflammation, and no significant bone resorption or new bone formation was evident. The peak response was reached after 3 intragingival infections. The mechanisms by which LTA caused the pathological alterations in the rat periodontium and the possible relations of this experimental model to periodontal disease in the human are discussed.

Experimental toxoplasmosis in young piglets

Piglets eight to 10 days old and one day old were infected with a cyst-forming strain of Toxoplasma gondii of low virulence. The older piglets developed an immunological response to the infection and survived, although inflammatory lesions were demonstrable in a variety of tissues. Some of the one-day-old piglets died; they exhibited more severe inflammatory lesions and lymphoid depletion in the lymph nodes, spleen and thymus. The tissue reaction resembled infection with a high-virulence strain of the organism. Control animals showed a delay in maturation of the lymphoid system during the first week of life. The virulence of the organism in therefore modified to a certain extent by the competence of the animal to develop an immunological response to the infection.

Experimental pulpitis in immunized monkeys

Bovine serum albumin (BSA) was topically applied to exposed dentin to assess whether inflammatory reactions can be induced in the pulp of monkeys immunized against BSA. Four cynomolgus monkeys received repeated injections of BSA emulsified with Freund's incomplete adjuvant. Pulp challenge was performed by applying BSA in freshly cut dentin cavities prepared on the buccal surface in 34 teeth. In 29 control teeth ovalbumin (OVA) was applied. Control applications of BSA were also performed in 15 teeth prepared in three nonimmunized monkeys. Forty-eight hours after the initiation of the pulp challenge the monkeys were sacrificed and the pulp tissue examined in the light microscope. Topical application of BSA to freshly exosed dentin in immunized monkeys resulted in severe inflammatory lesions in the pulp, characterized by bleeding and extravascular infiltration of large numbers of leukocytes. Extensive tissue damage was an important feature in several pulps. Identical applications of OVA in control teeth and BSA applications in nonimmunized monkeys produced no such reactions. The results indicate that interactions between antigens and antibodies can occur within the dentin-pulp area and following the formation of immune-complexes, severe injury to the pulp can be induced.

Experimental genital infection of male guinea pigs with the agent of guinea pig inclusion conjunctivitis and transmission to females.

Male guinea pigs were inoculated intraurethrally with the agent of guinea pig inclusion conjunctivitis (Gp-ic). Cytoplasmic inclusions were found in superficial epithelial cells of the urethra in smears and stained sections. Gp-ic antigen(s) was detected by immunofluorescent staining of sections. There was no marked urethral exudate, but many animals developed bullous lesions on the glans and the body of the penis and a severe inflammatory lesion of the hind leg. All males demonstrated an antibody response and most of them showed a positive skin test reaction. Venereal transmission to females of Gp-ic infection was shown to occur as determined by detection of inclusions in vaginal smears, antibody response, and positive skin tests.