Crk-associated substrate p130(Cas) interacts with nephrocystin and both proteins localize to cell-cell contacts of polarized epithelial cells.

Crk-associated substrate (p130(Cas), Cas) is a docking protein first recognized as having elevated phosphotyrosine content in mammalian cells transformed by v-Src and v-Crk oncoproteins. Subsequent studies have implicated Cas in the control of normal cell behavior through its roles in integrin-mediated signal transduction and organization of the actin cytoskeleton at sites of cell adhesion. In this study, we sought to gain new insight into normal Cas function by identifying previously unrecognized interacting proteins. A yeast two-hybrid screen using the C-terminal region of Cas as a bait identified the Src homology 3 (SH3) domain of the mouse "nephrocystin" protein-orthologous to a human protein whose loss of function leads to the cystic kidney disease familial juvenile nephronophthisis. The putative full-length mouse and partial canine nephrocystin sequences were deduced from cDNA clones. Additional studies using epitope-tagged mouse nephrocystin indicated that nephrocystin and Cas can interact in mammalian cells and revealed that both proteins prominently localize at or near sites of cell-cell contact in polarized Madin-Darby canine kidney epithelial cells. Our findings provide novel insight into the normal cellular activities regulated by both Cas and nephrocystin, and raise the possibility that these proteins have a related function in polarized epithelial cells.

Scars without wounds: spectrum of delayed manifestations of histoplasmosis outside of the endemic area.

This short series represents a spectrum of histoplasmosis usually described only in places where the infection is nearly universal. In fact, most of the patients in this series were born in such places (17 of 19 patients with complicated presentations; 2 had recent suspicious exposures). As young adults, they had moved away to pursue military life, usually in coastal areas where the evidence of infection with H. capsulatum is a statistical rarity. The implications of these observations are straightforward. At the clinical level, they focus on histoplasmosis as a possible cause of pulmonary, mediastinal, or other lesions of obscure etiology, whether or not the patient has recently lived in "the endemic area". The simple determination of CF gamma titers may heighten the index of suspicion, especially when not confounded by skin testing with histoplasmin, a practice which rarely provides useful information. [Table: see text] With regard to pathogenesis, it seems noteworthy that common form of histoplasmosis was not seen in this brief experience. That is the "marching cavity" described by Goodwin and Des Prez, and other forms of chronic cavitary disease. The absence of such lesions is consonant with the view that they require continuous exogenous infection for their development. As for the forms of histoplasmosis which were seen in this series, it appears that most of the illnesses developed outside of what is usually considered endemic areas. The term endemic, as construed medically, has been defined as "restricted to and constantly present in a particular country or locality". Such a construction is unduly pedantic and rigid for clinicians. A more probabilistic view is needed, with attention to the possible role of inapparent infection early in life and of environmental foci of infection in places where the organism is not notoriously present. The mobile nature of our society makes it likely that the radiographic manifestations of once-regional diseases such as this one will be encountered more generally than in the past.

A study of co-positivity of three multipuncture techniques with intradermal PPD tuberculin.

One hundred thirty-five patients with a reaction of 10 mm or more of induration to 5 TU of intradermal PPD were simultaneously tested with 3 multipuncture techniques to determine the copositivity of the multiple puncture methods with the Mantoux method. Of the 3 multipuncture preparations used (Tine Test, Aplitest, and Mono-Vacc), the Mono-Vacc had 2 (1.5 per cent) false-negative result after 48 hours with only one remaining negative result after 72 hours; whereas the Tine-Test had 21 (15.5 per cent), and the Aplitest had 13 (9.6 per cent) false-negative reactions after 48 hours. Vesicular eruptions were not a commonly noted reaction to the multipuncture preparations. Of the 3 multipuncture preparations commercially available, Mono-Vacc is the preferred reagent because of its significantly lower incidence of false-negative reactions.

Drowning and near-drowning. Pathophysiology and therapy.

Drowning is one of the three leading causes of accidental death. Dry drowning, the type in which no water enters the trachea, responds readily to resuscitation efforts. The current concept of drowning recognizes few differences between saltwater and freshwater aspiration; the therapeutic approach is the same for both types. The physician should be prepared to deal with the drowning victim at the scene of the accident as well as in the hospital. Hospitalization for observation is necessary in every instance, as adult respiratory distress syndrome may develop and cause secondary drowning.

Transient unilateral hypoperfusion of the lung following mediastinoscopy.

Two cases of pulmonary hypoperfusion occurring after mediastinoscopic examination were demonstrated on lung scans. In one case, this finding on the ninth day required a pulmonary angiographic study that yielded normal findings. Repeat lung scans were normal. We propose that localized mediastinal edema or bleeding after mediastinoscopic examination can produce defects of hypoperfusion, and we urge caution in the interpretation of lung scans up to nine days after mediastinoscopic examination.

Bronchiolar carcinoma: report of 11 cases and review of the literature.

Eleven cases of bronchiolar carcinoma seen between 1970 and 1975 are reviewed. Roentgenographic manifestations at the time of initial examination included single peripheral nodules, multiple nodules, irregular cavities and a persistent infiltrative form. Microscopic tissue examinations showed two patterns of tumor growth: a papillary form resembling tall columnar cells extending along but not invading the alveolar septal walls and a cribriform pattern represented by inflammatory thickening of the alveolar septal walls and pleomorphic cellular proliferation within luminal spaces. The papillary form was associated with the cavitary lesions. Long term survival is dependent on early recognition of the single peripheral nodule, cavity or small persistent infiltrative form managed by a thoracotomy and lobectomy.

Control of high density bacterial contamination of the fiberoptic bronchoscope.

In a double-blind study the fiberoptic bronchoscope was contaminated with five pathogenic organisms, each at a concentration of 10(9) organisms per milliliter. The shaft and inner channel of the bronchoscope were cleansed with five antiseptic regimens. Each regimen included equal 120-ml aliquots of one, two, or three solutions, respectively. The five different regimens were as follows: (1) physiologic saline solution; (2) 70 percent solution of isopropyl alcohol, followed by physiologic saline solution; (3) alkaline glutaraldehyde, followed by 70 percent solution of isoproply alcohol, followed by physiologic saline solution; (4) benzalkonium chloride, followed by 70 percent isopropyl alcohol, followed by physiologic saline solution; and (5) povidone-iodine solution, followed by 70 percent solution of isopropyl alcohol, followed by physiologic saline solution. The four regimens involving solutions other than saline solution alone were effective in reducing the count of residual bacterial colonies to 10(4) colonies per milliliter or less.

Bronchilar carcinoma in a 20-year-old man.

A 20-year-old man with a nine-month history of pulmonary abscess and hemoptysis was discovered to have a small nidus of bronchiolar carcinoma in the fibrotic reaction surrounding the pulmonary abscess. The cell type, origin, and occurrence of this tumor in fibrotic pulmonary disease are discussed. We believe that this case represents an unusual presentation of bronchiolar carcinoma with respect to clinical manifestation, tumor size, and patient's age.

Extrinsic allergic alveolitis after Aspergillus fumigatus inhalation. Evidence of a type IV immunologic pathogenesis.

Three weeks after a massive inhalation of mold present on infected oats, a farmer's wife had extrinsic allergic alveolitis. Aspergillus fumigatus was cultured from the moldy oats and from deep bronchial washings obtained at fiberoptic bronchoscopy. Spores and hyphae characteristic of Aspergillus species were demonstrated within granulomas in the pulmonary tissue obtained by transbrochial biopsy. Serum precipitins, delayed (48 hour) cutaneous hypersensitivity and in vitro lymphocyte transformation to A. fumigatus were demonstrated. The findings in this case suggest that a type IV immunologic response and subsequent (lymphocyte-mediated) tissue inflammation may underlie the pathogenesis of this and other forms of hypersensitivity pneumonitis.

Metastatic renal cell carcinoma 24 years after nephrectomy.

Recurrence of renal carcinoma 20 years after primary resection is uncommon. A patient is reported in whom two pulmonary metastases developed 24 years following nephrectomy for renal carcinoma. After a left lower lobectomy and a right pulmonary wedge resection were performed, he survived an additional two years before dying from metastatic disease.