Absence Of Lymphocytic Infiltration Research Articles

25. Short Term Maintenance of Cadaveric Costal Cartilage Integrity in Ear Reconstruction

PURPOSE: Cartilage allografts are widely used in orthopedic and reconstructive surgery. Concerns over resorption and warping have limited their use in ear reconstruction. Newer sterilization methods forgo high dose radiation yielding high quality allografts with reliable longevity. In this study, we evaluate the use of this non/minimally irradiated cadaveric costal cartilage (NCCC) for primary ear reconstruction in congenital type III microtia. METHODS: Patients who underwent ear reconstruction using NCCC between August 2020 and August 2022 were included. Demographics, complications, and outcomes were recorded. Pre and post implantation cartilage samples from four patients stained with H&E and safranin-O were analyzed qualitatively using light microscopy. RESULTS: 12 ears were reconstructed for 11 patients (six male, five female) with congenital type III microtia. Average age was 10.7 years (range 4 - 25) and average follow up time post stage I reconstruction was 11.1 months (range 1.5-25.3). Two instances of surgical site infection were recorded as well as two instances of 1cm x 1cm construct exposure which were successfully salvaged. All patients required less than 90 minutes of anesthesia and were discharged home same day with over-the-counter analgesics for pain. Histologic analysis revealed repopulation of empty lacuna at stage II with cells and absence of lymphocytic infiltration. CONCLUSION: Ear reconstruction with NCCC shows short term maintenance of cartilage integrity with evidence of integration on histology. Advantages over current options include significantly reduced anesthesia time, reduced post operative pain, same day discharge, and reconstruction as early as 4 years old. Longer follow up times will reveal long-term reliability.

Skin Tightening With Hyperdilute CaHA: Dilution Practices and Practical Guidance for Clinical Practice.

BackgroundOver the past several years, hyperdilute calcium hydroxylapatite (CaHA) has emerged as an effective modality for improving skin quality and managing laxity in the face, arms, hands, neck, décolletage, upper arms, abdomen, buttocks, and upper legs, as well as for treating cellulite and striae. Whereas undiluted CaHA is used to provide volume, hyperdilute CaHA is distributed across a much larger surface area in a more superficial plane to stimulate neocollagenesis and elastin formation over time. The absence of lymphocytic infiltrates and predominance of type 1 collagen in the tissue response to CaHA make hyperdilute CaHA a valuable tool for nonsurgical skin tightening.ObjectivesThe aim of this study was to provide practical step-by-step guidance on patient selection, dilution practices, and optimal injection technique to facilitate incorporation of the technique into clinical practice.MethodsOver the course of 3 regional meetings in the United States, 12 expert physician injectors participated in live webinars as part of a continuing medical education program.ResultsThe practical guidance in this manuscript is based upon the most frequently requested information by audience members and the information considered critical for success by the authors.ConclusionsThe minimally invasive nature of filler injection results in little downtime, making this treatment particularly appealing. The recommendations presented are consistent with previously published consensus guidelines on hyperdilute CaHA but are intended to serve as “how-to” guidance based on the experience of expert injectors who have successfully treated the face and body.Level of Evidence: 4

Endothelial monolayer disruption in bioprosthetic heart valve as a trigger of primary tissue failure

Aim . To study the surface and cellular composition of non-calcified bioprosthetic heart valve (BHV) leaflets with varying degrees of structural deterioration to determine the possible mechanisms of primary tissue failure development. Materials and methods . An examination of six bioprosthetic heart valves (KemCor and PeriCor) extracted from mitral position due to the structural valve deterioration was performed. The structure of BHV leaflets was studied by hematoxylin – eosin staining and immunohistochemistry assay (with the following indicators – CD3, T lymphocytes; CD20, B lymphocytes; CD31, mature endothelial cells; CD34, endothelial progenitor cells; CD68, monocytes/macrophages; vimentin, mesenchymal cells; α-smooth muscle actin, vascular smooth muscle cells). Results . The degree of disruption of BHV leaflets in primary tissue failure differed significantly: relatively intact samples with the intact endothelial monolayer, areas with impairment of the surface layers (minimal and moderate damage) and areas with the spread of destruction into the extracellular matrix of the leaflet (expressed degeneration) were determined. Endothelial cells (monolayer with preserved or impaired integrity), macrophages, smooth muscle cells and other mesenchymal lineage cells were identified in BHV. T- and B-lymphocytes were not detected in the BHV leaflets. Conclusions . A characteristic feature of structurally deteriorated BHVs is impairment of endothelial monolayer integrity in areas of degraded extracellular matrix. In contrast to other types of bioprosthetic dysfunctions, structural valve deterioration was characterized by the absence of lymphocyte infiltration. Therefore, we suppose that endothelial mololayer injury is a trigger of structural BHV deterioration.

The intestinal health of silver catfish Rhamdia quelen can be changed by organic acid salts, independent of the chelating minerals

Food additives based on organic acids or their salts promote numerous improvements in zootechnical parameters, digestive enzymatic activities, resistance to diseases and intestinal health. This study aimed to evaluate the influence of calcium and sodium chelated to propionic acid on the digestive enzymes activities, intestinal microbial community and histological alterations in the liver and intestine of the silver catfish Rhamdia quelen. Fish with an initial mean weight of 8.43 ± 0.18 g were divided into a control and four treatments, with 15 fish in each replicate, and fed the following supplemented diets for 60 days, four times per day: unsupplemented control, Ca-propionate 0.25% (Ca0.25%), Ca-propionate 1% (Ca1%), Na-propionate 0.25% (Na0.25%) and Na-propionate 1% (Na1%). At the end of the assay, digestive enzymes activities in the gastrointestinal tract (GIT) was not affected by the chelating mineral, nor by its concentration to propionic acid. On the other hand, the most important digestive enzymes for silver catfish were lipase and acid protease. Regarding the intestinal microbial community, fish fed Ca0.25% showed a lower concentration of total heterotrophic bacteria and a higher lactic acid bacteria count, compared to Na1%-supplemented fish, in addition to the maintenance of cordonal features and liver cholestasis. Fish fed a Ca0.25% or Na0.25% supplemented diet presented the best histomorphometry parameters, such as the greatest width and number of villi, a lower number of eosinophilic infiltrates and the absence of lymphocytic infiltrates. The organic acid propionate chelated to calcium at 0.25% improved the microbial composition and intestinal health of silver catfish, with no effects on the liver, the most important organ for depuration, and could be indicated as a feed additive for silver catfish.

Platelet Depletion is Effective in Ameliorating Anxiety-Like Behavior and Reducing the Pro-Inflammatory Environment in the Hippocampus in Murine Experimental Autoimmune Encephalomyelitis.

The neuropsychiatric symptoms of multiple sclerosis (MS), such as anxiety and depression, can result from disease activity itself as well as psychological reaction to an unfavorable diagnosis. Accordingly, the literature reports evidence of increased anxiety-like behavior in experimental autoimmune encephalomyelitis (EAE), an accepted MS model. Due to the recently described critical role of platelets in inflammation and autoimmune disease, we examined the relationship between platelets, inflammation, and anxiety-like behavior in EAE. In the elevated plus maze, EAE-induced C57BL/6J mice showed decreased time spent in the open arms relative to vehicle-only controls, demonstrating an increase in anxiety-like behavior. This effect occurred in the presence of platelet–neuron association, but absence of lymphocytic infiltration, in the hippocampal parenchyma. Platelet depletion at the pre-clinical disease stage, using antibody-mediated lysis prevented the EAE-induced increase in anxiety-like behavior, while no significant difference in distance moved was recorded. Furthermore, platelet depletion was also associated with reduction of the pro-inflammatory environment to control levels in the hippocampus and prevention of EAE disease symptomology. These studies demonstrate the high efficacy of a platelet-targeting approach in preventing anxiety-like symptoms and clinical manifestations of EAE and have implications for the treatment of neuropsychiatric symptoms in MS.

Major Histocompatibility Complex I and II Expression and Lymphocytic Subtypes in Muscle of Horses with Immune-Mediated Myositis.

BackgroundMajor histocompatibility complex (MHC) I and II expression is not normally detected on sarcolemma, but is detected with lymphocytic infiltrates in immune‐mediated myositis (IMM) of humans and dogs and in dysferlin‐deficient muscular dystrophy.Hypothesis/ObjectivesTo determine if sarcolemmal MHC is expressed in active IMM in horses, if MHC expression is associated with lymphocytic subtype, and if dysferlin is expressed in IMM.AnimalsTwenty‐one IMM horses of Quarter Horse‐related breeds, 3 healthy and 6 disease controls (3 pasture myopathy, 3 amylase‐resistant polysaccharide storage myopathy [PSSM]).MethodsImmunohistochemical staining for MHC I, II, and CD4+, CD8+, CD20+ lymphocytes was performed on archived muscle of IMM and control horses. Scores were given for MHC I, II, and lymphocytic subtypes. Immunofluorescent staining for dysferlin, dystrophin, and a‐sarcoglycan was performed.ResultsSarcolemmal MHC I and II expression was detected in 17/21 and 15/21 of IMM horses, respectively, and in specific fibers of PSSM horses, but not healthy or pasture myopathy controls. The CD4+, CD8+, and CD20+ cells were present in 20/21 IMM muscles with CD4+ predominance in 10/21 and CD8+ predominance in 6/21 of IMM horses. Dysferlin, dystrophin, and a‐sarcoglycan staining were similar in IMM and control muscles.Conclusions and clinical importanceDeficiencies of dysferlin, dystrophin, and a‐sarcoglycan are not associated with IMM. Sarcolemmal MHC I and II expression in a proportion of myofibers of IMM horses in conjunction with lymphocytic infiltration supports an immune‐mediated etiology for IMM. The MHC expression also occured in specific myofibers in PSSM horses in the absence of lymphocytic infiltrates.

Cricothyroid Articulation in Elderly Japanese With Special Reference to Morphology of the Synovial and Capsular Tissues

The present study aimed to clarify individual variations in the cricothyroid joint (CT joint). Using 30 specimens of the CT joint obtained from elderly donated cadavers, we examined the composite fibers of the capsular ligament as well as the morphology of the synovial tissue. The capsular ligament consistently contained abundant thick elastic fiber bundles on the anterior side of the joint (anterior band) and an elastic fiber-made mesh on the posterior side (posterior mesh). The synovial membrane, lined by synovial macrophages, was usually restricted to the recesses in the medial or inferior end of the joint cavity. Without the synovial lining, elastic fibers of the capsular ligament were subsequently detached, dispersed, and exposed to the joint cavity. We also observed a folded and thickened synovial membrane and a hypertrophic protrusion of the capsular ligament. In six specimens, the joint cavity was obliterated by debris of synovial folds and elastic fiber-rich tissues continuous with the usual capsular ligament. Notably, with the exception of two specimens, we did not find lymphocyte infiltration in the degenerative synovial tissue. We considered the CT joint degeneration to be a specific, silent form of osteoarthritis from the absence of lymphocyte infiltration. For high-pitched phonation, the elderly CT joint seemed to maintain its anterior gliding and rotation with the aid of elastic fiber-rich tissues compensating for the loss of congruity between the joint cartilage surfaces. Conversely, however, high-pitched phonation may accelerate obliteration of the joint.

Influence of lymphocitic thyroiditis on prognostic outcome differentiated thyroid carcinoma

Thyroid carcinoma is rare malignant tumors. They are typically presented with slow progression and clinical course. Lymphocytic infiltration, including fagocytosis of neoplastic cells by macrophage plays an important role in preventing development of distant metastases. This paper sets the following objectives: Establish whether presence or absence of Hashimoto thyroiditis in differentiated thyroid carcinoma (DTC) is a favourable prognostic factor. The group under examination here are all newly diagnosed patients with differentiated thyroid carcinoma surgically treated at the Surgery Clinic in Podgorica from 2003. to 2010. A total of 125 patients, aged 11 to 79, were included in this research. The patients were divided in two groups, those with and those without lymphocytic infiltration. Both groups were mutually compared for their prognostic factors. For the identification of T and B lymphocytes, anti-CD 3 and anti-CD 20 antibodies were used. Student t-test was used for comparison of clinical and pathological parameters among groups, Hi square test for comparison of frequency, and Coxs regression model for time dependant variables as frequency of recurrence among groups with various stages of disease. Survival curve (Kaplan-Meier) is used for comparison of time dependant variables (survival, recurrence, death). The follow-up time ranges from 10 to 70 months in both groups of patients. presence of lymphocytic infiltration in thyroid tissue in patients with differentiated thyroid carcinoma is significant prognostic factor (P < 0.0001). But, absence of lymphocytic infiltration is a poor prognostic factor in patients with invasive extra thyroid tumours (P < 0.0001). Also, absence of lymphocytic infiltration is a poor prognostic factor for development of lymphogenic and hematogenic metastases. The presence of T or B lymphocytes and varying degree of their presence is not a significant prognostic factor (P < 0.0046). Patients without lymphocytic infiltration are significantly more numerous in the fourth stage of disease (P < 0.0001). There is no statistically significant difference in terms of the presence of T or B lymphocytes in the tissue. Chronic lymphocytic thyroidis hahshimoto is a favourable prognostic factor in our examined group (P < 0.0001). Local invasiveness and extrathyroid expansion is significantly smaller in the group of patients with the presence of lymphocytic infiltration (P < 0.0001). By means of univariate analysis, we found that factors with a significant impact on survival rate include age (P < 0.0001), size of tumour (P < 0.018), extrathyroid invasiveness (P < 0.0001), hematogenic metastases (P < 0.049). Lymphocytic infiltration is present in 81% of patients in their thyroid gland, and in 19% patients there are no lymphocytes in tissue. Limphocitic infiltration has a favourable influence on tumor variables. CONCLUSION. This research has shown that lymphocytes in tissue as part of Hashimoto thzroiditis have an effect on certain prognostic factors of differentiated thyroid carcinoma as size, smaller invasiveness and extrathyroid tumour growth and incidence of hematogenic metastases.

Association Between Histological Type of Tumour Growth and Patient Survival in T2-T3 Lymph Node-Negative Rectal Cancer Treated with Sphincter-Preserving Total Mesorectal Excision

For rectal cancer patients without nodal metastases the identification of unfavourable factors can be helpful for the better selection for adjuvant therapy and multimodality treatment. The aim of this study was to evaluate the impact of clinico-histological parameters on prognosis in node-negative rectal cancer patients. One hundred and thirty-nine consecutive node negative rectal cancer patients with complete five-year follow-up were studied prospectively. All of them underwent curative anterior resection with total mesorectal excision technique. Seventy-eight patients with tumour penetration beyond the bowel wall received neo-adjuvant short-course radiation (25 Gy) followed by surgery within 1 week and postoperative chemotherapy with 5-fluorouracil and folinic acid in six cycles or adjuvant radiochemotherapy: irradiation (50.4 Gy) combined with chemotherapy (as above). Cancer-specific survival was calculated according to the Kaplan-Meier method. Variables significant in univariate analysis by log-rank test (P < 0.05) entered the Cox proportional hazard model. Survival was decreased for males, older patients (>60 years) with extraperitoneal, poorly differentiated cancers, tumours with mucinous histology and with the absence of lymphocytic infiltration but with the lack of statistical importance. Prognosis was significantly improved for patients with T2 tumours versus T3 (P < 0.01) and with cancers with expanding growth comparing to diffusely infiltrating ones (P < 0.01). In multivariate analysis these parameters significantly and independently influenced survival (P < 0.01 and P < 0.05, respectively). Diffusely infiltrating growth of tumour can reflect the more aggressive cancer behaviour and unfavourable course of disease despite the optimised local control. Apart from the extent of tumour penetration the type of invasive margin can be an additional parameter helpful for the optimal treatment planning and better patient selection for postoperative chemotherapy.

A Dukes/Jass combination – is it more discriminating?

In 1987 Jass described a modified staging system for colorectal cancer using two anatomical criteria in common with the Dukes system; extent of spread through the bowel wall and the presence or absence of lymph node involvement. Additionally it used two 'biological' criteria; the nature of the expanding margin of the tumour (pushing or infiltrating), and the presence or absence of lymphocytic infiltration within the tumour. This study aims to determine whether a combination of the Dukes and Jass staging systems provides a better predictor of five year survival in patients with colorectal cancer than Dukes stage alone. The Dukes and Jass stages along with vital status at five years were recorded for all 612 patients undergoing resection for colorectal cancer at the Royal Bolton Hospital and the Beaumont (BMI) Hospital, Bolton between 1991 and 1998. Kaplan-Meier survival curves with log rank test were used to show how survival correlated with Jass group stratified by Dukes stage. Both the Dukes B and the Dukes C tumours could be divided into groups with significantly different five year survival rates when stratified by Jass group. Five year survival for Dukes stage B, Jass group II tumours was 73.74% compared to Dukes B Jass III tumours whose survival was 51.38% (P = 0.0018). Five year survival for Dukes C Jass III tumours was 43.18% and for Dukes C Jass IV survival was 24.39% (P = 0.0029). By combining the biological criteria of the Jass staging system with the anatomically based Dukes system, both Dukes B and C tumours can be divided into groups with significantly different five year survival figures.

CXCR3 chemokine receptor immunoreactivity in primary cutaneous malignant melanoma: correlation with clinicopathological prognostic factors

Background: A role for CXCR3, the receptor for chemokines Mig, IP-10 and interferon-inducible T cell α-chemoattractant, in tumour cell migration during melanoma progression has been proposed. Aims: To analyse CXCR3...

Clinicopathological and immunohistochemical analysis of 20 cases of Merkel cell carcinoma in search of prognostic markers

To evaluate the clinicopathological and immunohistochemical characteristics of Merkel cell carcinoma (MCC) in an attempt to find new, potentially significant, prognostic markers. Clinical data and follow-up, histopathological features (pattern, cell size, thickness, mitoses, vascular invasion, lymphocytic infiltration) and immunohistochemical detection [CK20, thyroid transcription factor (TTF-1), chromogranin A, synaptophysin, p53, Ki67, Fli-1, CD99, c-Kit] were evaluated in 20 cases of MCC. Fli-1 and CD99 were detected in 90% and 55% of cases, respectively. Tumour size>30 mm, stage II, 'absent' lymphocytic infiltration, and the presence of>50% of Ki67+ tumour cells, were found to be prognostic indicators of disease-free interval (DFI), but only 'absent' lymphocytic infiltration constituted an independent prognostic factor of DFI after multivariate analysis. For overall survival, the same variables, together with local recurrence and lymph node involvement, had prognostic significance, with only local recurrence as an independent prognostic factor after multivariate analysis. Absence of lymphocytic infiltration and Ki67 immunoreactivity in more than 50% of tumour cells should be evaluated in conjunction with other well-known prognostic markers in MCC. Furthermore, recognizing that Fli-1 and CD99 expression is commonly found in MCC by immunohistochemistry may avoid misinterpretation in the differential diagnosis of MCC with other small round cell tumours.

MCP-1 and CCR2 Contribute to Non-Lymphocyte-Mediated Brain Disease Induced by Fr98 Polytropic Retrovirus Infection in Mice: Role for Astrocytes in Retroviral Neuropathogenesis

Virus infection of the central nervous system (CNS) often results in chemokine upregulation. Although often associated with lymphocyte recruitment, increased chemokine expression is also associated with non-lymphocyte-mediated CNS disease. In these instances, the effect of chemokine upregulation on neurological disease is unclear. In vitro, several chemokines including monocyte chemotactic protein 1 (MCP-1) protect neurons from apoptosis. Therefore, in vivo, chemokine upregulation may be a protective host response to CNS damage. Alternatively, chemokines may contribute to pathogenesis by stimulating intrinsic brain cells or recruiting macrophages to the brain. To investigate these possibilities, we studied a neurovirulent retrovirus, Fr98, that induces severe non-lymphocyte-mediated neurological disease and causes the upregulation of several chemokines that bind to chemokine receptors CCR2 and CCR5. Knockout mice deficient in CCR2 had reduced susceptibility to Fr98 pathogenesis, with significantly fewer mice developing clinical disease than did wild-type controls. In contrast, no reduction in Fr98-induced disease was observed in CCR5 knockout mice. Thus, signaling through CCR2, but not CCR5, plays an important role in Fr98-mediated pathogenesis. Three ligands for CCR2 (MCP-1, MCP-3, and MCP-5) were upregulated during Fr98 infection of the brain. Antibody-blocking experiments demonstrated that MCP-1 was important for retrovirus-induced neurological disease. In situ hybridization analysis revealed that MCP-1 was expressed by glial fibrillary acidic protein-positive astrocytes. Thus, astrocytes, previously not thought to play an effector role in the disease process were found to contribute to pathogenesis through the production of MCP-1. This study also demonstrates that chemokines can mediate pathogenesis in the CNS in the absence of lymphocytic infiltrate and gives credence to the hypothesis that chemokine upregulation is a mechanism by which retroviruses such as human immunodeficiency virus induce neurological damage.

Rabbit experimental sensory ataxic neuropathy: anti-GD1b antibody-mediated trkC downregulation of dorsal root ganglia neurons

We previously reported experimental sensory neuropathy in rabbit induced by the immunization of ganglioside GD1b. The major pathological change in diseased rabbits was degeneration of primary sensory neurons with central axons extending to the dorsal column of the spinal cord. The loss of primary sensory neurons that mediate proprioceptive sensation prompted us to investigate the expression of trkC in dorsal root ganglia (DRG) because this type of neuron is thought depend mainly on neurotrophin-3-mediated trkC signaling. Northern blotting analysis revealed markedly reduced expression of trkC in DRG of diseased rabbits in acute phase. This result together with the absence of lymphocytic infiltration in DRG of diseased rabbits at any stage suggests the anti-GD1b antibody-mediated downregulation of trkC expression could be one of the pathogenesis of this experimental sensory ataxic neuropathy.

Prognostic evaluation of DNA flow cytometric and histopathologic parameters of colorectal cancer

The clinical value of DNA flow cytometry of colorectal cancer is unclear. The purpose of this retrospective study was to evaluate the relationship between tumor flow cytometry, histopathologic parameters, and survival. Flow cytometry was performed on paraffin embedded specimens from 653 patients who had surgery from 1980 to 1983. Aneuploidy was associated with distal tumor, perineural invasion, desmoplastic reaction, and failure to secrete mucin. TNM Stage I tumors were more frequently diploid than were more advanced tumors (71% vs. 41%). An abnormal DNA content had a marginal impact on survival as evaluated by univariate analysis (69% vs. 61% 10-year survival rate, P = 0.06). Multivariate analysis revealed that significant predictors of outcome were lymph node metastasis (95% confidence interval of relative risks of death from recurrent disease, 1.50-2.92), rectal cancer (1.22-2.19), absence of lymphocytic infiltration (1.20-2.17), invasion through bowel wall (1.17-3.13), lymphatic vessel invasion outside bowel wall (1.05-2.69), perineural invasion (1.15-3.19), and male gender (1.00-1.79). These findings suggest that ploidy is associated with some histopathologic parameters, but flow cytometry does not correlate with long term survival of patients with colorectal carcinoma.

Anatomical and functional consequences of induced rejection of intracranial retinal transplants

Retinae from embryonic rats transplanted over the midbrain of newborn host rats establish connections with visual centres of the host brain, which mediate a pupilloconstrictor response in the host eye when the transplant is stimulated by light. The changes in the size of the host pupil can be measured accurately with a pupillometry system. We have taken advantage of the additional observation that while grafts between rat strains, as between Long Evans and Sprague-Dawley strains, may survive indefinitely, they can be induced to reject by skin grafting from the strain providing the donor retinal tissue. Combining pupillometry with skin grafting provides a useful way of examining correlated anatomical and behavioural changes associated with graft rejection from its earliest stage to the point of overt destruction. Even within three days of skin grafting, the amplitude and speed of constriction as well as the response latency all showed significant enhancement from normal, and this was sustained for a further week or more. Response deterioration followed during the second week post-skin grafting, but the exact timing varied considerably among animals. Anatomical observations of the process of retinal rejection showed the first invasion of lymphocytes to occur between days 5 and 7 and total degeneration of the retinal transplant and its projections to occur by two to three weeks post-skin grafting. The lymphocytic infiltration was preceded by upregulation of microglia, which expressed both class I and II major histocompatibility antigens and by activation of astrocytes identified by their expression of glial fibrillary acidic protein. Within the target region of retinal transplant axons, major histocompatibility antigen expression and astrocytic responses preceded degeneration of transplant derived axons (demonstrated by the Fink-Heimer stain) and there was no evidence for any lymphocytic infiltration during transplant rejection. These observations show that the earliest stages of microglial activation are accompanied by an enhancement of response parameters, but that the functional failure finally occurs only at an advanced stage of graft destruction. The absence of lymphocytic infiltration into areas receiving terminals from axons of transplant origin, even though these contain significant numbers of reactive microglia, suggests that the terminal axonal processes are not a primary target for the immune response.

Nonimmune thyroid destruction results from transgenic overexpression of an allogeneic major histocompatibility complex class I protein.

The overexpression of major histocompatibility complex (MHC) class I molecules in endocrine epithelial cells is an early feature of autoimmune thyroid disease and insulin-dependent diabetes mellitus, which may reflect a cellular response, e.g., to viruses or toxins. Evidence from a transgenic model in pancreatic beta cells suggests that MHC class I overexpression could play an independent role in endocrine cell destruction. We demonstrate in this study that the transgenic overexpression of an allogeneic MHC class I protein (H-2Kb) linked to the rat thyroglobulin promoter, in H-2Kk mice homozygous for the transgene, leads to thyrocyte atrophy, hypothyroidism, growth retardation, and death. Thyrocyte atrophy occurred in the absence of lymphocytic infiltration. Tolerance to allogeneic class I was revealed by the reduced ability of primed lymphocytes from transgenic mice to lyse H-2Kb target cells in vitro. This nonimmune form of thyrocyte destruction and hypothyroidism recapitulates the beta-cell destruction and diabetes that results from transgenic overexpression of MHC class I molecules in pancreatic beta cells. Thus, we conclude that overexpression of MHC class I molecules may be a general mechanism that directly impairs endocrine epithelial cell viability.

Morphological demonstration of the failure of Mus caroli trophoblast in the Mus musculus uterus.

A histological study of Mus caroli embryos gestating in the Mus musculus uterus was undertaken at Day 8.5 of gestation, 1 day after such embryos are reported to be normal and 1 day before the earliest events associated with death of the xenogeneic embryos. In comparison to control M. caroli embryos recovered from M. caroli and to control M. musculus embryos recovered from M. musculus, the xenogeneically transferred embryos showed intrauterine growth retardation that was associated with trophoblastic insufficiency. Trophoblast cell degeneration was observed, in the absence of lymphocytic infiltration. Therefore, loss of trophoblast cell function rather than lymphocyte-mediated destruction of trophoblast appears to underlie the death of M. caroli embryos in the M. musculus uterus.

Participation of T lymphocyte in corneal edema in the early stage of herpetic stromal keratitis.

The participation of T lymphocytes in the immunopathogenesis of corneal opacity in herpetic stromal keratitis was investigated. In BALB/c mice infected intracorneally with herpes simplex virus type 1, corneal opacity was manifested 10 days after infection, while in athymic mice corneas remained almost clear. Histologically, all opaque corneas revealed stromal edema accompanied by the diffuse presence of polymorphonuclear cells and lymphocytes. When complement (C')-treated immune spleen cells were adoptively transferred into athymic mice 6 or 72 h after corneal infection, stromal keratitis with mild opacity was observed 10 days after transfer. The athymic mice given anti-Thy 1.2+C'-treated immune spleen cells failed to develop corneal opacity. The difference, as revealed by light and electron microscopy, was the presence or absence of lymphocytic infiltration and edema in the posterior third layers of the stroma and endothelial lesions. The endothelium was infiltrated by lymphocytes or macrophages and showed various stages of destruction. The main cause of corneal opacity in the early stage of herpetic stromal keratitis is thought to be stromal edema due to an adverse effect on the endothelium by immune T lymphocytes.