Marked Epithelial Hyperplasia Research Articles

Synchronous presentation of borderline phyllodes tumour and tubular adenoma in a background of fibrocystic disease - A case report

Mammary fibroepithelial lesions encompass a wide spectrum of tumours ranging from an indolent fibroadenoma to potentially fatal malignant phyllodes tumour. Here, we report a case of 22 -year -old unmarried girl with bilateral breast lump for one month who underwent wide local excision which on histopathological examination revealed borderline phyllodes tumour and tubular adenoma in a background of fibrocystic disease with adenosis, marked epithelial hyperplasia, fibro adenomatoid change and apocrine metaplasia a rare occurrence which can be confused with benign and malignant lesions of the breast.

Granulomatosis with polyangiitis presenting with strawberry gingivitis: Images in rheumatology

A 17 years old girl presented with complaints of painful, swollen and bleeding gums. On examination, she had diffuse reddish nodular gingival swelling with dusky margins that bleed (Figure 1). Her inflammatory markers were high, including markedly elevated anti-PR3 (147.2 AU/ml). The gingival biopsy revealed marked epithelial hyperplasia with ulceration, and the CECTchest showed bilateral nodular cavitary lesions, thus confirming our diagnosis for Granulomatosis with Polyangiitis. The patient received rituximab and methylprednisolone, and the symptoms had started resolving on the follow-up post a fortnight.

Repetitive Ozone Exposures and Evaluation of Pulmonary Inflammation and Remodeling in Diabetic Mouse Strains.

Background:Epidemiological studies support the hypothesis that diabetes alters pulmonary responses to air pollutants like ozone (). The mechanism(s) underlying these associations and potential links among diabetes, , and lung inflammation and remodeling are currently unknown.Objectives:The goal was to determine whether pulmonary responses to repetitive ozone exposures are exacerbated in murine strains that are hyperglycemic and insulin resistant.Methods:Normoglycemic and insulin-sensitive C57BL/6J mice; hyperglycemic, but mildly insulin-resistant, KK mice; and hyperglycemic and markedly insulin-resistant KKAy mice were used for ozone exposure studies. All animals were exposed to filtered air (FA) or repetitive ozone ( , 4 h/d, for 13 consecutive weekdays). Tissue analysis was performed 24 h following the final exposure. This analysis included bronchoalveolar lavage (BAL) for cell and fluid analysis, and tissue for pathology, immunohistology, mRNA, and hydroxyproline.Results:Following repetitive exposure, higher bronchoalveolar lavage fluid inflammatory cells were observed in all mice (), with a notable influx of neutrophils and eosinophils in KK and KKAy mice. Although the lungs of -exposed C57BL/6J and KK mice had minimal centriacinar histological changes without fibrosis, the lungs of -exposed KKAy mice contained marked epithelial hyperplasia in proximal alveolar ducts and adjacent alveoli with associated centriacinar fibrosis. Fibrosis in -exposed KKAy lungs was confirmed with immunohistochemistry, tissue hydroxyproline content, and tissue mRNA expression of fibrosis-associated genes (Ccl11, Il13, and Mmp12). Immunofluorescence staining and confocal microscopy revealed alterations in the structure and composition of the airway and alveolar epithelium in regions of fibrosis.Discussion:Our results demonstrate that in diabetic animal strains repetitive ambient ozone exposure led to early and exaggerated pulmonary inflammation and remodeling. Changes in distal and interstitial airspaces and the activation of Th2 inflammatory and profibrotic pathways in experimental animals provide a preliminary, mechanistic framework to support the emerging epidemiological associations among air pollution, diabetes, and lung disease. https://doi.org/10.1289/EHP7255

EVALUATION OF THE WOUND HEALING ACTIVITY OF CAESALPINIA BONDUCELLA AND CYCLEA PELTATA EXTRACTS IN EXPERIMENTALLY INDUCED DIABETIC RATS

Objective: The present study was conducted to verify the effect of Caesalpinia bonducella and Cyclea peltata extracts on experimentally induced excision wounds in diabetic rats.Methods: Methanolic and ethyl acetate extract of test sample in PEG base was applied and observed for wound healing effect for a period of 15 d.Results: The data demonstrated statistically significant wound contraction up to 98% in the treated sample as compared to 90% in diabetic control group. The results correlated (r ³ 0.95) with fasting blood glucose level, indicating the deleterious effect of hyperglycemia in wound healing. Histopathological studies indicated moderate granulation with marked epithelial enclose and moderate hyperplasia in groups treated with high dose (100 mg/kg BW) of methanolic extract of aerial part of Cyclea peltata and root of Caesalpinia bonducella. Conclusion: From the study, it can be hypothesized that tested plant extracts favours wound healing in diabetic animals and paves the way for the more detailed study of the phytochemical constituent for therapeutic applications. The present investigation adds to the existing knowledge in the field of therapeutic medicine and may even become the base for the development of herbal based gel formulations or ointments for treating wounds in diabetic patients and thereby continuous usage of synthetic drugs, its associated side effects could be avoided.

Telfairia occidentalis Leaf and Seed Extracts as Possible Preventive and Therapeutic Agents for Induced Benign Prostatic Hyperplasia

The efficacy of Telfairia occidentalis leaf and seed as herbal extracts in the management of induced benign prostatic hyperplasia (BPH) in Wistar rats was investigated. Fifty adult male Wistar rats in 10 equal groups were utilized for the study. BPH was induced in nine groups. One group, (CN) served as normal control and the last, (CI) as positive control. Groups ALC and ELC respectively had aqueous and ethanolic extracts of the leaf while ASC and ESC groups had the respective seed extracts. All these four groups had concurrent administration of the extracts. Groups ALP, ELP, ASP and ESP had the respective extract administered after induction of BPH. At the expiration of the experiment, blood samples were collected for leukocyte count and estimation of activities of antioxidants. The animals were sacrificed and the harvested prostate glands processed for light microscopy. Groups ELC and ESP had significantly lower body weight change compared to CI ( P< 0.05 ). The mean prostate weights of ALP, ALC, ELC, ASC and ESC were significantly higher than that of CN ( P< 0.05 ). The MDA levels of ALP, ELP, ASP, ESP, ELC and ASC were significantly lower than CI but markedly higher than that of CN. The glutathione peroxidase, catalase and superoxide dismutase activities of ALP, ELP, ASP, ESP, ALC, ELC, ASC and ESC were significantly higher than that of group CI but lower than CN ( P< 0.05 ). The histology of the prostate gland of groups CI and ELC showed marked epithelial and stromal Hyperplasia. Groups ASC, ESC and ALC showed lesser degree of epithelial and stromal hyperplasia. Telfairia occidentalis extracts (seed and leaf) are able to reduce the severity of the associated prostatitis, ameliorate the testosterone effects and reduce the size of prostate with Benign Hyperpasia by prevention of oxidative stress

Sex steroid receptors and apoptosis-related proteins are differentially expressed in polycystic ovaries of adult dogs

In Polycystic Ovaries (PCOs), the dynamics of sex hormone receptors and follicle-related apoptotic signaling remain unknown. In this study, we investigated the expression of androgen receptors (AR), estrogen receptors (ERα and ERβ), and apoptosis-related molecules (BAX, active caspase-3, Bcl-2 and Survivin) on different follicular stages of PCOs in adult dogs. Clinical evidences of high estradiol and testosterone levels, persistent estrus and vaginal discharge were observed. Inhibin B immunolabeling was increased in primary and 2 to 5-mm follicles, and a marked epithelial hyperplasia was common in the ovarian surface. Ovarian epithelia and primary follicles showed low expression of AR, ERα, and ERβ, whereas a moderate immunoexpression of AR was found in theca cells of secondary follicles and cysts. In PCOs, growing follicles displayed ERα expression, and secondary follicles exhibited higher ERβ expression. In addition, while few ERα-positive cells were found in the cysts, ERβ was moderately expressed in growing follicles and cysts. BAX was upregulated in the ovarian epithelium, primary follicles, and in the wall of follicular cysts. Active caspase-3 was significantly downregulated in the epithelium, primary follicles, and follicular cysts, whereas growing follicles had a strong immunoexpression in the granulosa cells. Bcl-2 and survivin were increased in the epithelium and primary follicles, and only survivin was upregulated in secondary and growing follicles. While Bcl-2 had a diffuse immunexpression in the follicular cysts, survivin was overexpressed by these cells. We concluded that sex steroid receptors and apoptotic proteins are differentially expressed in the follicles of adult dogs with PCOs.

Cyanide-induced hyperthyroidism in male Wistar rats.

Background:Cyanide is one of the major environmental pollutants termed thyroid disruptor. Regardless of its origin, it is a primary toxic agent. This study was designed to understand the impact of prolonged low dose cyanide exposure on the structure and function of the thyroid gland.Materials and Methods:Twelve F1 male Wistar rats were used for this study. They were divided into two groups of six animals each. The first group served as the control group and received 0.25M sucrose while the second group being the treated group received 2 mg/kg body weight (BW) potassium hexacyanoferrate III solution. The treatment duration was 56 days following which the animals were sacrificed by cervical dislocation. Blood samples were drawn to determine serum FT3, FT4 and thyroid stimulating hormone (TSH) levels. The thyroid gland was also excised and processed for light microscopic studies.Result:An increase in serum FT3 and FT4 with decrease serum TSH was obtained in the treated group. Application of one-way analysis of variance (ANOVA) statistical analysis showed that there were highly significant differences (P < 0.05) in the activities of FT3, FT4 and TSH when compared with those of the control group. Light microscopic examination of thyroid gland from the treated group revealed marked epithelial hyperplasia with cellular degeneration and scanty cytoplasm while the control group revealed normal thyroid architecture.Conclusion:Results obtained revealed that hyperthyroidism was induced by cyanide.

Pathology of spontaneous air sacculitis in 37 baboons and seven chimpanzees and a brief review of the literature.

Air sacculitis is an important clinical condition in non-human primates. We evaluated 37 baboons and seven chimpanzees with spontaneous air sacculitis submitted to pathology over a 20-year period. Air sacculitis was observed almost exclusively in males. Common reported signs were halitosis, coughing, nasal discharges, depression, anorexia, and weight loss. Gross lesions included thickened air sacs and suppurative exudate lining the walls. Microscopic lesions included marked epithelial hyperplasia or hypertrophy, necrosis, fibrosis, cellular infiltrates, and bacterial colonies. Mixed bacterial infections were more common than infections by single species of bacteria. Streptococcus sp. was the most frequent bacteria isolated in both baboons and chimpanzees. This is the first report describing the gross and microscopic lesions of air sacculitis in chimpanzees. The preponderance of males suggests a male sex predilection in baboons.

Sheep Pox Virus Induces Proliferation of Type II Pneumocytes in the Lungs

The present study investigated the expression of pulmonary surfactant proteins (surfactant protein [SP]-A, SP-B, proSP-C), thyroid transcription factor-1 (TTF-1), proliferating cell nuclear antigen (PCNA) and the infiltration of CD3(+) T and CD79alphacy(+) B lymphocytes into the lungs of 10 lambs naturally infected with sheep pox virus. Microscopical examination detected marked epithelial hyperplasia, sheep pox cells and neutrophilic infiltration in pock nodules. Immunohistochemistry demonstrated intense expression of SPs in the cytoplasm of the hyperplastic type II pneumocytes in the nodular pock lesions. These cells displayed a gland-like arrangement. The hyperplastic and the normal bronchiolar epithelium did not express SPs. The nuclei of the hyperplastic and normal type II pneumocytes labelled positively for TTF-1. Strong PCNA positivity indicated epithelial cell proliferation in the pock nodules. Moderate to abundant numbers of CD3(+) T cells, but few CD79alphacy B lymphocytes, were detected in the pock lesions. Transmission electron microscopy revealed that the hyperplasia in the pock nodules comprised predominantly type II pneumocytes and that the sheep pox cells and epithelial cells contained virus particles in their cytoplasm. The results of this study show that sheep pox virus induces marked proliferation of type II pneumocytes and bronchiolar epithelial cells and that the lung lesions in diseased lambs are mainly proliferative.

Multiple cutaneous inverted papillomas in a dog : clinical communication

Cutaneous inverted papillomas are described in an 8-month-old mixed breed domestic dog from Windhoek, Namibia. Multiple firm, rapidly growing, doughnut-shaped masses formed on the ventral abdomen, which histologically consisted of a cup-shaped rim of marked epithelial hyperplasia, giant keratohyaline granules and prominent koilocytes and marked hyperkeratosis filling the centre of the mass. Current literature on canine papillomas is briefly reviewed.

Pattern of distribution of intraductal and infiltrating ductal carcinoma: A three-dimensional study using serial coronal giant sections of the breast

The purpose of this study was to establish the 3-dimensional (3D) structure of the breast tissue and to study the distribution and relationship between the intraductal and infiltrating components of ductal carcinoma and other proliferative epithelial lesions of the breast. Thirty mastectomy specimens with infiltrating carcinoma less than 3.0 cm in diameter were serially cut in the coronal plane. Each giant section was divided into small sections for routine processing. Using Photoshop (Adobe) and PowerPoint (Microsoft) software programs, the routinely stained sections were scanned and assembled to reestablish complete giant sections of the breast and subsequently the 3D structure. Intraductal and infiltrating ductal carcinomas, epithelial hyperplasia with atypia, and marked epithelial hyperplasia without atypia were mostly confined to a single duct (27 cases), resulting in an increase in size of the involved breast segment. Three remaining cases included a case of Paget's disease with tumor appearing to spread from one duct system to another system through the epidermis and two cases with multiple separate foci of carcinomas located in different quadrants and accompanied by ductal spread in different lactiferous ducts. Both intraductal and infiltrating carcinomas were often located in the superficial segments (near the subcutaneous tissue) (28 cases). The infiltrating components were often located adjacent to area of pure intraductal carcinoma and were often peripheral (nearer the chest wall than the nipple). Intraductal carcinomas showed a “fanned out” pattern of distribution, frequently extended toward the nipple (with involvement of the nipple or subareolar tissue in 7 cases), and occasionally were seen in the breast tissue peripheral to the infiltrating carcinoma. Multiple ducts with intraductal carcinoma could be seen to be connected with each other with serial sections. However, in at least 6 cases, foci of intraductal carcinomas were separated from each other by segments of duct with benign epithelium. Breast carcinoma often arise from the breast segment close to the subcutaneous tissue. Infiltrating carcinoma lesser than 3.0 cm in diameter is usually located adjacent to the area of pure intraductal. The pattern of spread of intraductal carcinoma has a pyramid-like shape, with the summit toward and occasionally extending up to the nipple. These findings should be considered in the surgical strategy for segmental resections of breast carcinomas.

Regression and epithelial hyperplasia after myopic photorefractive keratectomy in a human cornea

We present the histology of a cornea of a woman who had excimer laser photorefractive keratectomy (PRK) for myopia 6 months before she died in an accident. Preoperative spherical refraction was −6.00 diopters (D) with an astigmatism of −0.50 D. Six months postoperatively, refraction was −4.50 D. Slight corneal haze was noted at 1 and 3 months. The corneal histology showed marked epithelial hyperplasia in the center of the ablation zone without subepithelial deposition of newly synthesized collagen, proteoglycans, or both. The epithelial thickness was 38 μm in the untreated area and 93 μm in the center of the ablation. In conclusion, postoperative epithelial hyperplasia was responsible for regression after PRK in this eye.

Chronic rhinitis associated with herpesviral infection in captive spur-thighed tortoises from Spain.

An epidemic of chronic rhinitis in a population of 50 captive spur-thighed tortoises (Testudo graeca graeca) from Palafrugell (Girona, Spain) is described, in which eight animals died and 12 were euthanatized to perform necropsies and post-mortem studies. The main clinical sign was a bilateral, seromucous rhinitis often accompanied by stomatitis and glossitis. Hematology and serum biochemistry were performed in 33 of the 50 ill animals and in 29 healthy tortoises from three disease-free populations. Lymphocyte count, aspartate aminotransferase (AST) activity, and alpha-globulin levels were significantly higher in the animals from the sick population. The heterophil count was significantly lower in the sick animals. Some of the diseased tortoises also showed a normocytic-normochromic anemia. Lesions were restricted to the respiratory system and oral cavity. Marked epithelial hyperplasia and presence of a severe mixed inflammatory infiltrate in the epithelium of the oral, nasal, and tracheal mucosae were observed. Electron microscopy demonstrated the presence of intracytoplasmic and intranuclear viral particles of the size, shape, and distribution pattern typical of a herpesvirus.

Scanning Electron Microscopy and Pathogenicity ofChilodonella piscicola(Ciliophora) on Juvenile Salmonids

Abstract An ectoparasitic ciliate, Chilodonella piscicola (=C. cyprini), became epizootic and caused chronic mortalities in juvenile masu (cherry) salmon Oncorhynchus masou and pink salmon O. gorbuscha being reared at the Nemuro Hatchery, eastern Hokkaido, Japan, in the spring of 1988. Cumulative mortalities amounted to 20% in a masu salmon population over 5 months and 10% in a pink salmon population over 2 months. Transmission experiments in masu salmon fry confirmed that C. piscicola can cause severe proliferation of the gill epithelium in the absence of other stressors. The infected fish exhibited reduced growth and chronic mortalities after the mean intensity had reached a peak (619 parasites per fish) at week 4 postinfection. The marked epithelial hyperplasia was followed by intense fusion of adjacent gill lamellae and filaments. Respiratory failure due to gill epithelial hyperplasia may have been a primary cause of the deaths.

Spermidine radioimmunoassay in monitor of precancerous lesions of esophagus

Serum spermidine was assayed by radioimmunoassay in different stages of esophageal carcinogenesis in the population from high risk area of esophageal cancer, Linxian County. The serum spermidine values were 76.94 +/- 74.38 ng/ml in 36 normal individuals; 115.71 +/- 113.45 ng/ml in 35 patients with marked epithelial hyperplasia (MEH) and 294.48 +/- 135.36 ng/ml in 31 patients with early esophageal cancer. Patients with MEH were given intervention treatment by Aminoretinoic Ester or Anticancer B or placebo (Starch) as controls. One year later, samples from the population were collected again for serum spermidine measurement. The values were 95.8 +/- 68.2 ng/ml in 27 normals; 125.1 +/- 72.9 ng/ml in 62 patients with MEH treated by Anticancer B; 125.6 +/- 117.2 ng/ml in 64 patients with MEH by Aminoretinoic Ester; 162.4 +/- 76.6 ng/ml in 62 controls and 210.5 +/- 182.9 ng/ml in 44 patients with early esophageal cancer. The results showed that spermidine radioimmunoassay could reflect the tendency of esophageal precancerous changes toward cancer or back to normal. They can be taken as a mid-way monitor indicator for tumor-blocking drugs. Also, it could be of value in the early diagnosis of esophageal cancer.

Pathogenicity and Immunogenicity of Mynah Pox Virus in Chickens and Bobwhite Quail

An avian pox virus was isolated from cutaneous proliferative lesions removed from greater hill mynahs (Gracula religiosa) imported from Malaysia. Cutaneous inoculation of specific pathogen-free chickens and bobwhite quail with the mynah pox virus resulted in severe proliferative cutaneous lesions similar to those seen in the naturally infected mynah birds. Microscopically, the reaction in the chickens and quail at sites of virus inoculation was characterized by marked epithelial hyperplasia with ballooning degeneration and formation of cytoplasmic inclusion bodies. Inoculation of conjunctival and oral mucosae of chickens by applying pox virus with a cotton swab did not result in gross or microscopic lesions.In cross-protection studies, chickens and bobwhite quail immunized with either quail, fowl, pigeon, turkey, or psittacine pox vaccines were not protected from challenge with mynah pox virus. Following vaccination of quail and chickens with mynah pox virus vaccine, there was no resistance to challenge by quail, fowl, pigeon, turkey, or psittacine pox viruses. Significant protection against development of lesions following inoculation with mynah pox virus was attained only when the homologous virus was used as a vaccine.

Respiratory (especially pulmonary) and urinary infections ofCryptosporidiumin layer chickens

Respiratory (especially pulmonary) and urinary infections of Cryptosporidium were diagnosed in four of 26 chickens from a layer flock. Macroscopically, the lungs had various degrees of yellowish white pneumonic foci. Occasionally caseous exudates were present in the lungs and air sacs. Histologically, there was marked epithelial hyperplasia in the air capillaries, atria, parabronchi, secondary bronchi and trachea. Cryptosporidia were detected on the epithelial cell surface or in the lumens of them in the lungs. Macrophages containing cryptosporidia were frequently seen in the lumens and walls of air capillaries and atria and in the cavities of parabronchi and secondary bronchi. Cellular infiltration was observed in the interstitium. Aspergillosis or bacterial infection was also present in the lungs and air sacs. The ureters and collecting ducts, collecting tubules and distal convoluted tubules of the kidneys demonstrated marked hyperplasia of epithelial cells associated with cellular infiltration. Cryptosporidial attachment on the epithelial cell surface of them were noted. Ultrastructurally, trophozoites, schizonts and macrogametocytes of Cryptosporidium were recognised in the lungs, kidneys and ureters. This study suggests that Cryptosporidium may induce bronchopneumonia with epithelial hyperplasia and may invade the urinary tract of chickens that are infected with other infectious agents.

Multistage transformation of cultured rat urothelium: the effects of N-methyl-N-nitrosourea, sodium saccharin, sodium cyclamate and 12-O-tetradecanoylphorbol-13-acetate

Rat bladder epithelial cell transformation was found to involve at least three distinct phenotypic stages in vitro. The effects on this process of N-methyl-N-nitrosourea (MNU), sodium saccharin, sodium cyclamate and 12-O-tetradecanoylphorbol-13-acetate (TPA) alone or in combination were investigated. MNU was a potent inducer of proliferating preneoplastic epithelial foci. Sodium saccharin alone induced a transient hyperplastic response of the cultured urothelium but did not induce significantly more foci than in controls, though a late toxic effect of saccharin may have masked focus induction. In combination with a single dose of 250 micrograms/ml MNU, sodium saccharin did not increase focus incidence compared with MNU treatment alone but following a single treatment with 25 micrograms/ml MNU which alone induced no foci, saccharin induced a significant number of foci indicating a promoting effect under these conditions. Sodium cyclamate alone induced a marked and prolonged epithelial hyperplasia and a significant increase in focus incidence above controls and above MNU-treated cultures. Following a single treatment with 250 micrograms/ml MNU, cyclamate increased focus incidence still further. TPA, the potent skin tumour promoting agent, alone induced significantly more foci than in controls. Rapidly-proliferating cell lines were established from nine foci induced by treatment with MNU alone or MNU + saccharin. Four of these were tumorigenic. These results indicate that MNU is a potent inducer of preneoplastic foci in rat urothelial cultures. Sodium saccharin and sodium cyclamate can act as promoting agents in this in vitro system as in the in vivo induction of tumours and sodium cyclamate appears to be active as a complete inducer under these conditions.

Ultrastructure of mast cells in the hyperplastic buccal mucosa of the zinc‐deficient rat

As previously reported, young rats on zinc-deficient diets develop a marked epithelial hyperplasia in the mucosa of the cheek, associated with a four-fold increase in the number of mast cells in the lamina propria. We now report the results of a quantitative and qualitative ultrastructural study of these mast cells. In contrast to the cells in mast cell-related disease, the cells were of normal morphology, but of consistently increased size, containing proportionally increased numbers of mitochondria and specific granules. The size distribution of the granules was as in controls. Microvilli were lengthened in proportion to the increase in the cell circumference. The number of nuclear pores was increased but their spacing was as in controls. In all these measurements, the experimental mast cells were a remarkably homogeneous population. We conclude that mast cells are capable of developing into cells of larger size showing evidence of greater activity. It may be that this development occurs in response to the same (unknown) stimulus which causes their number to increase. By virtue of their increased number and size, mast cells may play an important role in the enhancement of the microcirculation commonly seen in conditions of epithelial hyperplasia.

Acute bronchiolar injury following nitrogen dioxide exposure: A freeze fracture study

Three groups of Syrian golden hamsters were exposed to NO 2 for 6, 24, or 48 hr to determine acute effects on intercellular junctional morphology in distal airways and alveolar epithelium. A fourth group, exposed for 48 hr, was allowed to recover for 2 days prior to sacrifice. Light and transmission electron microscopy of bronchiolar epithelium show ciliary loss and surface membrane damage, loss of ciliated cells, and epithelial flattening at 24 and 48 hr. Moderate to marked epithelial hyperplasia and nonciliated cell hypertrophy are noted after 48 hr. Some restoration of normal histoarchitecture is noted in bronchioles of animals allowed a 48-hr recovery period. Freeze fracture platinum-carbon replicas of bronchiolar epithelium show the gradual evolution of a severe disruption of tight junctional networks after 6, 24, and 48 hr of exposure. Following 2 days of “recovery,” bronchiolar tight junctions from animals exposed for 48 hr remain fragmented. The wide distribution of the junctional material present suggests a regenerative process. Freeze fracture replicas of bronchial epithelium show similar fragmentation of tight junctions following 6-hr exposures. After longer intervals, however, there is a return to more normal appearances. Duration of NO 2 exposure has no systematic effect on the integrity of tight junctions in alveolar epithelium. The findings suggest that disruption of tight junctions may be an important specific determinant of increased bronchiolar epithelial permeability following brief exposures to nitrogen dioxide.