Mesenchymal hamartoma and undifferentiated embryonal sarcoma: diagnostic keys that radiologists need to know. / Hamartoma mesenquimatoso y sarcoma embrionario indiferenciado: claves diagnósticas que el radiólogo debe conocer.

OBJECTIVE: Hepatic tumors are uncommon in pediatric patients. Among the most common of these uncommon tumors are mesenchymal hamartoma and undifferentiated embryonal sarcoma, which have different origins but similar appearance on imaging studies. This paper reviews the characteristic findings and differential diagnosis of these entities. Ultrasonography is the first-line imaging test to study these tumors. Magnetic resonance imaging and computed tomography are useful for further characterizing the tumors and planning surgery. CONCLUSION: Radiologists need to be familiar with the imaging findings of the different disease entities and to evaluate them together with the patient's age, personal history, and bloodwork.

Dissociation of preparatory attention and response monitoring maturation during adolescence.

OBJECTIVE: Substantial brain development occurs during adolescence providing the foundation for functional advancement from stimulus-bound "bottom-up" to more mature executive-driven "top-down" processing strategies. The objective was to assess development of EEG markers of these strategies and their role in both preparatory attention (contingent negative variation, CNV) and response monitoring (Error Related Negativity, ERN, and Correct Related Negativity, CRN). METHODS: CNV, ERN and CRN were assessed in 38 adolescents (18 girls), age 11-18 years, using a variation of a letter discrimination task. RESULTS: Accuracy increased with age and developmental stage. Younger adolescents used a posterior attention network involved in inhibiting irrelevant information. Activity in this juvenile network, as indexed by a posteriorly-biased CNV and CRN decreased with age and advancing pubertal development. Although enhanced frontal CNV, known to be predictive of accuracy in adults, was not detected even in the older adolescents, top-down medial frontal response monitoring processes (ERN) showed evidence of development within the age-range studied. CONCLUSIONS: The data revealed a dissociation of developmental progress, marked by relatively delayed onset of frontal preparatory attention relative to error monitoring. SIGNIFICANCE: This dissociation may render adolescents vulnerable to excessive risk-taking and disinhibited behavior imposed by asynchronous development of component cognitive control processes.

Aberrant p53 expression in feline vaccine-associated sarcomas and correlation with prognosis.

Eighty spontaneously occurring feline vaccine-associated sarcomas (VAS) were evaluated to determine the immunohistochemical expression of the tumor suppressor gene p53. Sixty-five of 80 VAS (81%) exhibited positive immunoreactivity with Mab240, a murine monoclonal antibody that specifically recognizes mutated p53. Only 44 of 81 tumors (55%) were positive with rabbit polyclonal antibody CM-1. CM-1 often yielded nonspecific staining of nonneoplastic tissues. Nonspecific staining was greatly reduced or absent with Mab240. Cytoplasmic staining for p53 was a consistent pattern of VAS, occurring in 44% of tumors evaluated. Cats with tumors that exhibited cytoplasmic p53 had significantly shorter time to tumor recurrence compared to those cats with tumors that exhibited nuclear p53 staining (P = 0.0284), but no significant difference in survival outcome was observed. Immunohistochemical detection of p53 offers a prognostic tool for VAS, and, because abnormal p53 expression appears to be a common feature of feline VAS, molecular targeting of mutant p53, may offer a promising new therapeutic opportunity for this cancer.

Lung transplantation in interstitial lung disease.

Interstitial lung disease is a heterogeneous group of illnesses, some of which may progress to a fibrosing stage and cause respiratory failure. For selected candidates, lung transplantation is the ultimate therapeutic option. We review data on lung transplantation for various interstitial lung diseases. We address indications, procedures, and outcomes for patients undergoing transplantation. Unique issues affecting morbidity, mortality, and recurrence of disease are discussed. We review the literature of transplantation for specific interstitial lung diseases and the outcomes of transplantation for interstitial lung diseases. Candidates with idiopathic pulmonary fibrosis experience high mortality on the waiting list, but derive significant survival benefit from lung transplantation. Recurrence is reported for several interstitial lung diseases after lung transplantation. Survival with lung transplantation for interstitial lung diseases is comparable with that attained in recipients with other indications. Lung transplantation is a well-tolerated, effective therapy for respiratory failure in interstitial lung disease.

Pulmonary complications in cardiac transplant recipients.

BACKGROUND: The incidence of pulmonary complications in heart transplant recipients has not been extensively studied. We report pulmonary complications in 159 consecutive adult orthotopic heart transplantations (OHTs) performed in 157 patients. MATERIALS AND METHODS: Retrospective review of medical records. RESULTS: Forty-seven of 159 recipients (29.9%) had 81 pulmonary complications. Pneumonia was the most common (n = 27), followed by bronchitis (n = 15), pleural effusion (n = 10), pneumothorax (n = 7), prolonged respiratory failure requiring tracheotomy (n = 7), and obstructive sleep apnea syndrome (n = 6). All patients with late-onset (> 6 months after transplantation) community-acquired bacterial pneumonia presented with fever, cough, and a new lobar consolidation on the chest radiograph, and responded promptly to empiric antibiotics without undergoing an invasive diagnostic procedure. In contrast, early-onset nosocomial bacterial pneumonias carried a 33.3% mortality rate. A positive tuberculin skin test result was associated with a significantly higher rate of pulmonary complications (62.5% vs 26.8%, p = 0.007). Lung cancer and posttransplant lymphoproliferative disorder (PTLD) developed exclusively in 6 of the 61 patients (8.1%) who received induction immunosuppression with murine monoclonal antibody (OKT3). CONCLUSION: Pulmonary complications are common following heart transplantation, occurring in 29.9% of recipients, and are attributed to pneumonia of primarily bacterial origin in one half of cases. Late-onset community-acquired pneumonia carried an excellent prognosis following empiric antibiotic therapy, suggesting that in the appropriate clinical setting invasive diagnostic procedures are unnecessary. Analogous to reports in other solid-organ transplant recipients, induction therapy with OKT3 was associated with an increased incidence of lung cancer and PTLD. Overall, the development of pulmonary complications after OHT has prognostic significance given the higher mortality in this subset of patients.

The incidence of chickenpox in the community. Lessons for disease surveillance in sentinel practice networks.

Sentinel practice networks have been established in many European countries to monitor disease incidence in the community. To demonstrate the value of sentinel networks an international study on the incidence of chicken pox has been undertaken. Chickenpox was chosen as an acute condition for which incidence data are important to the determination of health policy on vaccine use. The project examined the incidence of chickenpox reported in sentinel networks in England and Wales, The Netherlands, Portugal and Spain (two regional networks) in January-June 2000 and the potential underestimate from patients who did not consult. An investigation of secondary household contact cases was undertaken. Reported incidence of chickenpox (all ages) in England and Wales was 25 per 10,000, in The Netherlands 13 per 10,000, in Portugal 21 per 10,000, in Spain Castilla y Leon 27 per 10,000 and in Spain Basque 55 per 10,000. Analysis of secondary contact cases suggested underestimation of incidence between 2.4% in Spain Castilla y Leon and 32.2% in The Netherlands. There was a trend towards incidence at an earlier age in England and Wales and in The Netherlands compared with Portugal and Spain. Whilst there was little problem in reliably identifying the number of incident cases in the recording networks and relating the non-consulting contact cases to them, the security of the denominator remains a problem where networks are comprised of differing categories of health care provider. It is essential that numerator and denominator information are made available specifically for each category.

Immunostimulatory effects of human recombinant interleukin-12 on peripheral blood mononuclear cells from normal dogs.

Interleukin-12 (IL-12) plays a pivotal role in regulating cellular immune responses involving autoimmunity, infectious disease, and cancer. Human recombinant (hr) IL-12 is being evaluated for therapy of human cancer. We investigated the potential of hrIL-12 to activate canine peripheral blood mononuclear cells (PBMC) using proliferation and cytotoxicity as readouts. Human rIL-12 caused increased proliferation of PBMC, and enhanced lysis of allogeneic canine tumor targets mediated by PBMC from normal dogs in vitro. In addition, antibody-dependent cellular cytotoxicity (ADCC) mediated by canine PBMC was enhanced by hrIL-12. These results indicate that hrIL-12 is recognized by canine immune cells, triggering a number of immune responses in canine PBMC, that may be important for immunotherapy of canine cancer. Information from this investigation provides impetus for evaluation of the effects of hrIL-12 on PBMC from tumor-bearing dogs and should be helpful in the development of hrIL-12 as an immune cell activator in vivo in the dog.

GD3 ganglioside antibody augments tumoricidal capacity of canine blood mononuclear cells by induction of interleukin 12.

Monoclonal antibody R24 recognizes ganglioside GD3 expressed on the cell surfaces of some tumor cells and on a subset of human T lymphocytes. Binding of R24 to these lymphocytes induces proliferation, cytokine production, and activation of intracellular signaling pathways. In the current report, we investigated expression of gangliosides by canine mononuclear immune cells and studied the ability of antiganglioside antibody to activate these cells using tumor cell killing as a measure of activation. A subset of canine monocytes, but not lymphocytes, was found to express gangliosides GD3 and GD2 as determined by the binding of monoclonal antibodies R24 and 14.G2a, respectively. Only R24 augmented the tumoricidal potential of fresh canine peripheral blood mononuclear cells (PBMCs) against tumor cell lines that did not express surface gangliosides GD3 or GD2. The augmenting effect of R24 on PBMC-mediated tumor cytotoxicity required cooperation between monocytes and lymphocytes because there was no enhancement of cytotoxicity mediated by R24 combined with either monocytes or lymphocytes individually. The enhancing effect of R24 on canine PBMC-mediated tumor cytotoxicity was blocked by anti-interleukin (IL)-12 neutralizing antibody, suggesting that R24 binding to monocytes triggered IL-12 release, contributing to the observed tumor killing effects. Reverse transcription-PCR confirmed that the binding of R24 to canine monocytes induced transcription of mRNA for canine IL-12. These data indicate that monocytes can be activated for tumoricidal responses through a membrane structure associated with ganglioside GD3 triggered by the binding of R24 and that the mechanism for enhanced cytotoxicity is due to the production and secretion of IL-12.

Sarcoidosis and transplantation.

BACKGROUND AND AIM OF WORK: Organ transplantation is an accepted treatment for patients with end-stage organ failure. There is limited information about transplantation in patients with sarcoidosis. While there has been no systematic study of transplantation in sarcoidosis, there have been several reports of patients with sarcoidosis undergoing organ transplantation. The purpose of this review is to analyze the available literature. METHODS: We reviewed the literature regarding transplantation of kidney, liver, heart, heart-lung and lung in patients with sarcoidosis with attention to survival, complications and the incidence of recurrence of sarcoidosis in the transplanted organ and at distant sites. RESULTS: Survival and complication rates are similar to those of patients undergoing transplantation for other indications. Recurrence of pulmonary sarcoidosis has been estimated to be 47% following lung transplantation. The published cases represent a fraction of the patients reported to the International Registry maintained by the United Network of Organ Sharing (UNOS). CONCLUSIONS: Transplantation can be carried out safely in patients with sarcoidosis. Recurrence is frequent, often asymptomatic, and does not compromise graft function or patient survival. Radiographic abnormalities or symptoms associated with recurrence are responsive to increased adrenocorticosteroid therapy. Exacerbation of sarcoidosis in transplant recipients occurs in the setting of intense immunosuppression.

Conversion of non-iodine-concentrating differentiated thyroid carcinoma metastases into iodine-concentrating foci after anticancer chemotherapy.

We present the unusual case of a 29-year-old man diagnosed in 1975 with papillary carcinoma of the thyroid metastatic to regional lymph nodes. The patient underwent surgical resection, postoperative iodine-131 (131I) radioablation and levothyroxine suppression. He was subsequently lost to follow-up. In 1991, he presented with extensive metastatic disease that was not demonstrable on whole-body 131I imaging, but was seen on computerized tomography and whole-body thallium chloride scanning. The patient was treated with cisplatin (Platinol) and doxorubicin (Adriamycin). Repeat 131I imaging after three cycles of chemotherapy showed significant 131I uptake in previously non-iodine-concentrating lesions. The patient was subsequently treated with 200 mCi 131I. We postulate this patient's non-iodine-concentrating thyroid cancer may have become functional by either a differentiating effect of chemotherapy on the tumor cells, or perhaps a selective cytotoxicity against nonfunctional, less differentiated papillary thyroid cancer cells, or both. This would allow more functional differentiated cells to overgrow and become the predominant cell type in the lesions. Chemotherapy may be beneficial in patients with advanced non-iodine-concentrating differentiated thyroid carcinoma by inducing radioiodine uptake and allowing subsequent radioiodine therapy. The possible mechanisms of induction of iodine uptake by chemotherapy are discussed.

Characterization of the protective borreliacidal antibody response in humans and hamsters after vaccination with a Borrelia burgdorferi outer surface protein A vaccine.

Significant borreliacidal antibody was induced in volunteers and hamsters 60 days after primary and secondary vaccination with high concentrations of recombinant outer surface protein A (rOspA). However, the borreliacidal antibody response waned rapidly. Only 1 person had detectable cidal activity 180 days after vaccination. Similarly, the borreliacidal antibody response waned rapidly in hamsters by week 10 of vaccination. By contrast, the total anti-rOspA antibody response remained elevated in volunteers and hamsters. When isolates of Borrelia burgdorferi sensu lato were incubated in sera from vaccinated humans or hamsters, only the vaccine-specific isolate was killed. These results were confirmed by challenging rOspA-vaccinated hamsters with different isolates of B. burgdorferi sensu lato. The results showed that monitoring total rOspA antibody is inappropriate for evaluating the efficacy of an rOspA vaccine. The rOspA vaccine must be improved to yield comprehensive protection and maintain sustained levels of protective borreliacidal antibodies.

Sarcoidosis mythology.

BACKGROUND: Sarcoidosis continues to be shrouded by anecdotal misinformation which has gained credence by repetition. These myths have been developing for the past 50 years and continue to accumulate, despite remedial data. Among the most egregious myths are that sarcoidosis is a disease of Blacks, that the chest radiography is diagnostic of sarcoidosis, and has chronologic significance, that serum angiotensin converting enzyme and bronchoalveolar lavage are diagnostic of sarcoidosis and serve as guides to therapy, that the Kveim-Siltzbach test is not a reliable diagnostic test for sarcoidosis, that sarcoidosis is difficult to diagnose, and that sarcoidosis is tuberculosis. METHODS AND RESULTS: The literature regarding these myths has been reviewed and supported by the experience with more than 10,000 patients with sarcoidosis who have been treated at Mount Sinai Medical Center, New York. CONCLUSIONS: Sarcoidosis occurs with varying frequency among all races. The chest radiograph typical of sarcoidosis can be mimicked by other granulomatous and neoplastic diseases. The classic radiographic stages, from 0 to 111, do not reflect the time course of sarcoidosis can be made relatively easily in most patients, but its etiology is still unknown.

Excessive thoracic computed tomographic scanning in sarcoidosis.

BACKGROUND: The clinical value of computed tomographic (CT) scanning of the chest in the initial assessment of sarcoidosis was investigated. METHODS: One hundred consecutive patients referred to the sarcoidosis outpatient services of the Mount Sinai Medical Center, New York from 1990 to 1992 with a presumptive diagnosis of sarcoidosis were studied. The diagnosis was subsequently confirmed in all by a positive tissue biopsy sample or the Kveim-Siltzbach test. Clinical and laboratory data of each patient were reviewed. Chest radiographs were classified according to the classical stages of sarcoidosis. Thirty five of the 100 patients had a CT scan of the chest performed before presentation. The CT scans were compared with the presenting clinical data and standard chest radiographs in order to determine if they yielded useful additional information regarding diagnosis or treatment. RESULTS: The chest CT scan revealed no additional clinically relevant information compared with conventional chest radiographs in any of the 35 studies performed. In two patients mediastinal adenopathy was detected by CT scan which was not seen on standard radiographs. Two patients thought to exhibit hilar adenopathy and pulmonary infiltrations by standard radiography had no parenchymal disease on the CT scan. Bilateral parenchymal infiltrates were seen in one patient which were interpreted as unilateral infiltrates by standard radiographs. The variance between conventional radiographs and CT scans in these five patients was not clinically valuable. CONCLUSIONS: CT scans of the chest do not add clinically useful information to the standard chest radiographs in the initial assessment of sarcoidosis in patients presenting with the typical standard radiological patterns. CT scanning of the thorax is indicated in patients with proven or suspected sarcoidosis when the standard chest radiographs are normal or not typical of sarcoidosis, when signs or symptoms of upper airway obstruction are present, when the patient has haemoptysis, if there is a suspicion of a complicating second intrathoracic disease, or the patient is a candidate for lung transplantation.

Dobutamine thallium 201 perfusion imaging in candidates for lung transplantation.

BACKGROUND: Thallium-201 stress imaging is the most often used noninvasive test for detection of coronary artery disease. Its utility in patients with end-stage lung disease has not been defined. METHODS: Feasibility, safety, and reliability of thallium 201 perfusion imaging was evaluated in 23 consecutive candidates for lung transplantation. All underwent graded dobutamine thallium 201 single photon emission computed tomography imaging. The perfusion imaging results were correlated with results of coronary angiography, radionuclide angiography, and right heart catheterization. RESULTS: The testing was completed without complications in all patients. No perfusion abnormality was detected in five patients, and none had evidence of coronary artery disease on coronary angiography. In 18 patients with abnormal thallium 201 imaging, coronary artery disease was detected in four patients only, and no angiographic data was available in three patients. Thus, in at least 11 of 23 patients, thallium 201 imaging was falsely positive. There was a trend toward lower left ventricular ejection fraction in patients with abnormal thallium 201 imaging. No correlation was found between thallium 201 results, pulmonary artery and right atrial pressures at rest. Possible noncoronary origin of the perfusion defects include the following (1) presence of sarcoid in the myocardium, (2) left ventricular attenuation by hypertrophied right ventricle, and (3) altered left ventricular anatomy, function, and coronary perfusion as a result of right ventricular pressure overload. CONCLUSIONS: Dobutamine thallium 201 stress test can be safely performed in lung transplant candidates. However, its specificity for detection of coronary artery disease is low. Selective use of coronary angiography in patients with multiple risk factors is likely a more cost-effective approach.

Upregulation of interferon-induced indoleamine 2,3-dioxygenase in human macrophage cultures by lipopolysaccharide, muramyl tripeptide, and interleukin-1.

The tryptophan decyclizing enzyme indoleamine 2,3-dioxygenase (IDO) was induced in human monocyte-derived macrophages (MDM) treated with human recombinant interferon-beta (IFN-beta) or interferon-gamma (IFN-gamma). Treated cells exhibited dose-dependent increases in IDO when assayed 48 hr after treatment. Cells exposed to IFN-gamma were observed to exhibit consistently higher peak levels of IDO when compared with cells incubated in the presence of IFN-beta. When IFN-beta-treated cells were incubated in the presence of specified amounts of bacterial lipopolysaccharide (LPS) or liposome-encapsulated muramyl tripeptide (MTP), peak IDO activity increased such that enzyme activity was comparable to maximal activity observed with IFN-gamma-treated cells. LPS and MTP also upregulated IFN-gamma-mediated IDO activity when suboptimal amounts of IFN-gamma were used. When macrophages were costimulated with various concentrations of human recombinant interleukin 1 alpha (IL-1 alpha), along with either maximum-stimulating amounts of IFN-beta or suboptimal amounts of IFN-gamma, IDO activity was upregulated in a manner similar to results obtained using the microbial products as stimuli. While neither IL-1 alpha or IL-1 beta was detected in culture supernatants from macrophages treated with either LPS or MTP (alone or in combination with IFN), IL-1 alpha was detected in cell lysates of macrophages treated with these upregulators. Although neutralizing antibody to IL-1 alpha abolished the upregulatory effect of exogenous IL-1 alpha, it had no effect on upregulation by LPS or MTP. This suggests that although LPS and MTP may induce production of cell-associated IL-1 alpha, upregulation of IDO activity by these agents is independent of IL-1 alpha production and may be mediated through distinct pathways.

[Incidence of Campylobacter spp. and Salmonella spp. in raw and roasted chicken in Guadalajara, Mexico]. / Incidencia de Campylobacter spp. y Salmonella spp. en pollo crudo y rostizado en Guadalajara, México.

The presence of Campylobacter spp. and Salmonella was studied in 70 samples of fresh retail chicken pieces and in 40 samples of roast chicken. Total plate count was performed in every sample as well. Most of the samples of fresh chicken yielded total plate counts > 10(8)/piece (thigh), while in roast chicken these counts ranged from 10(3) to 10(5)/piece (leg and thigh). Campylobacter was isolated from 33% of fresh chicken and from no sample of roast chicken. Salmonella was isolated from 69% of fresh chicken and 2.5% of roast chicken. There was no relationship between total plate counts in fresh chicken and isolation of either Campylobacter or Salmonella. Sixty percent of the Salmonella isolates belonged to serotype S. anatum, and about 50% of the isolates of Campylobacter were identified as being C. coli. The only Salmonella-positive sample of roast chicken yielded three serotypes: S. give, S. muenster, and S. manhattan. Presence of Campylobacter and Salmonella in chicken is of concern, due to the risk of spreading from the raw food to other cooked foods. The isolation of pathogens from roast chicken indicates mishandling during processing and/or storage of the product.

Changes in follicle-stimulating hormone secretion in spontaneously hypertensive rats.

FSH and testosterone plasma levels, pituitary FSH content and concentration and the weight of testis, seminal vesicles and ventral prostate have been studied at the ages of 30, 60 and 90 days in spontaneously hypertensive rats (SHR) and normotensive control (WKY) rats. In vitro FSH secretion by pituitaries, and the response to orchidectomy and to exogenous administration of either LHRH (1 microgram) or LHRH agonist (0.05, 0.1, 1, and 5 micrograms/kg) were analyzed in 90-day-old SHR and WKY male rats. Ventral prostate weight and FSH plasma levels were determined in other groups of adult male rats castrated and castrated and implanted for 15 days with silastic capsules containing testosterone, dihydrotestosterone or estradiol. Also FSH plasma levels and pituitary FSH concentration were determined at the ages of 30, 60 and 90 days in SHR and WKY female rats. Male SHR showed increased plasma FSH levels and high testicular weight in all the cases, and enhanced testosterone levels in plasma and pituitary FSH content on days 60 and 90. Weight of seminal vesicles and ventral prostate was normal or reduced, depending on the animal age. Adult SHR had increased FSH secretion in vitro, normal response to orchidectomy and did not exhibit FSH increases after LHRH administration. The efficiency of testosterone to stimulate ventral prostate growth and the ability of estradiol to reduce FSH plasma levels were decreased in SHR. Female SHR showed a significant increase in the pituitary content of FSH on day 30 and on proestrus at the ages of days 60 and 90.(ABSTRACT TRUNCATED AT 250 WORDS)

Diffuse pulmonary uptake of indium-111-labeled leukocytes in drug-induced pneumonitis.

Indium-111-labeled-leukocyte scintigraphy was performed on three febrile patients, two of whom had no signs or symptoms referable to the respiratory tract. The third patient had dyspnea on exertion, unchanged over two months. Their past histories were remarkable in that all three had recently undergone chemotherapy for malignancy (2 lymphoma, 1 malignant thymoma). Diffuse pulmonary uptake of labeled leukocytes was observed in all three individuals. As a direct result of leukocyte imaging, all three underwent fiberoptic bronchoscopy and transbronchial biopsy. The final diagnosis in each of these patients was drug-induced pneumonitis, which responded to treatment with corticosteroids. This entity should be added to the group of conditions, both infectious and noninfectious, that cause diffuse pulmonary uptake on labeled leukocyte images. Moreover, in the appropriate clinical setting, even in the absence of pulmonary signs or symptoms, diffuse pulmonary uptake of labeled leukocytes should alert the physician to the possibility of drug-induced pneumonitis.

Induction of emphysema in hamsters by intratracheal instillation of cathepsin B.

Current theories of pathogenesis suggest that pulmonary emphysema develops in humans because of progressive loss or derangement of lung elastin through a process mediated by elastolytic enzymes released by inflammatory cells. Neutrophils are considered primary etiologic factors because these cells produce and release two potent serine proteinases that cause emphysema when instilled into the lungs of animals. It has been suggested that alveolar macrophages also contribute to the development of emphysema through production of several enzymes with elastolytic activity, including the lysosomal cysteine proteinases cathepsin B and cathepsin L, but this has not been verified experimentally. In the current study, we instilled 115 micrograms of active cathepsin B into the lungs of hamsters three times at 48-h intervals. After 6 wk microscopic evaluation revealed that lung sections of five of seven animals given cathepsin B contained focal areas of enlarged and distorted alveoli, in the absence of fibrosis, which were similar to changes seen in the lungs of animals given papain intratracheally. Morphometrically, mean linear intercept (micron) values were significantly higher (p less than 0.025) in animals given cathepsin B (204.4 +/- 20.8) as compared with control animals (173.2 +/- 7.8), and internal surface area (sqcm) values were significantly lower (935 +/- 120 versus 1,083 +/- 56 in control animals), thereby confirming that airspace enlargement had developed after instillation of the enzyme. Lung volumes (ml) and compliance (ml/cm H2O) were not significantly higher in animals given cathepsin B.(ABSTRACT TRUNCATED AT 250 WORDS)

Goblet cell hyperplasia in large intrapulmonary airways after intratracheal injection of cathepsin B into hamsters.

Goblet cell hyperplasia (GCH) is a frequent histologic finding in the airways of smokers. Experimental observations suggest that the process may be caused by increased proteinase activity in the airways. To investigate the possible role of cathepsin B in the development of GCH, male Syrian golden hamsters were given three intratracheal injections of bovine spleen cathepsin B or buffer (pH 5.5) at 2-day intervals. Six weeks later, we found by review of PAS-hematoxylin-stained 1-micron sections of plastic-embedded lung tissue that large intrapulmonary airways of animals given cathepsin B contained a significantly greater number of secretory cells per millimeter of airway (64.8 +/- 7.3 versus 47.5 +/- 10.3 for control animals, p less than 0.005) in association with a significant increase in the number of total cells per millimeter of airway, from 149 +/- 14 for control animals to 164 +/- 11 for cathepsin-B-treated animals (p less than 0.025). No change was observed in the number of ciliated cells (93.9 +/- 8.1/mm for control animals versus 94.8 +/- 10.3/mm for cathepsin-B-treated animals) or other cells (3.0 +/- 2.2/mm for control versus 4.3 +/- 4.1/mm for cathepsin B), indicating that selective expansion of the secretory cell population occurred. In contrast, in the main bronchi of animals given cathepsin B, no significant alterations were found in the number or percentage of secretory cells. The findings reveal that cathepsin B induces secretory cell hyperplasia in hamsters and suggest the possibility that cysteine proteinases may contribute to GCH in smokers.