Early increase in expression of surfactant protein A gene in type II cells from silica-treated rats.

Silica is known to cause an increase in lung surfactant and to promote type II cell hypertrophy and hyperplasia. Two populations of type II cells can be isolated from silica-treated rats: type IIA cells that are similar to normal type II cells and type IIB cells that are larger, contain more surfactant phospholipids, and have increased rates of phospholipid biosynthesis. As much less is known about the influence of silica on the amounts of surfactant proteins (SPs) in type II cells, we examined expression of the genes for all four SPs in types IIA and IIB cells isolated from rats 1, 3, and 7 days after a single intratracheal injection of silica. There was a rapid increase in expression of the SP-A gene in type II cells from the silica-treated animals. SP-A mRNA content was 8- to 10-fold greater in types IIA and IIB cells isolated 1 day after silica injection than in type II cells from saline-injected animals. SP-A mRNA levels were also elevated in the cells isolated on days 3 and 7 after silica injection, but the extent of the increase was less than in the cells isolated on day 1 and declined with time after injection. SP-B, SP-C, and SP-D mRNA levels were 2.5- to 4-fold greater in type IIA cells on day 3 after silica injection than in control type II cells. However, those mRNA levels were not significantly increased in the type IIA cells isolated on days 1 and 7 or in type IIB cells at any time point. These data show that silica causes a rapid and substantial increase in expression of the SP-A gene in type II cells.

Computed axial tomography pancreatitis: an atypical asymptomatic postoperative disease without serum or urinary enzyme evaluation.

A case report of atypical postoperative pancreatitis following radical prostatectomy without any clinical symptoms is presented. The patient was asymptomatic in the postoperative period with regards to pancreas disease. Serum lipase, serum amylase and urinary amylase were normal. There was no history of alcoholism or biliary disease. The diagnosis was made by a CAT scan performed for an unrelated indication. The patient was followed for 17 months postoperatively. The pancreas CAT scan appearance returned to normal. No definitive treatment was given.

Altered regulation of surfactant phospholipid and protein A during acute pulmonary inflammation.

Biochemical changes in the pulmonary surfactant system caused by exposure to toxicants are often accompanied by an influx of inflammatory cells into the lungs. We have investigated the possibility that the inflammatory and surfactant biochemical effects might be connected. Co-treatment with dexamethasone, a synthetic anti-inflammatory glucocorticoid, mitigated the increases in free cells and total intracellular surfactant phospholipid normally seen in animals given silica alone, suggesting a relationship between the free cell population of the alveoli and the surfactant system during alveolitis. Furthermore, we have investigated whether induction of the surfactant system is a universal response to alveolar inflammation. Inflammation was induced in the lungs by intratracheal injections of titanium dioxide, silica, bleomycin or lipopolysaccharide (LPS) suspended in isotonic saline. Inflammatory cell and surfactant responses were measured at 3 days and 14 days following injection. There was a distinct alveolar inflammatory cell profile following administration of each agent, at each time point, indicating a dynamic inflammatory cell population during the course of the study. Furthermore, surfactant phospholipid and protein A (SP-A) pools exhibited unique responses to the inflammatory agents. Only silica-treated lungs maintained elevated levels of surfactant phospholipids and SP-A throughout the course of the experiment. We conclude that both the surfactant components and the inflammatory cell population of the alveoli undergo dynamic changes following treatment with these inflammatory agents and that activation of the surfactant system is not a universal response to alveolar inflammation, since surfactant components were not always elevated during times of increased alveolar cellularity. The unique inflammatory cell infiltrate elicited by silica is of particular interest in that surfactant components were elevated throughout the course of the experiment in this group. Indeed, we have shown that the size of the intracellular pool of surfactant is directly proportional to the number of polymorphonuclear leukocytes but not alveolar macrophages or lymphocytes in the alveoli following silica treatment. Finally, our data suggest that the phospholipid and SP-A components of surfactant respond differentially to the pulmonary toxicants in this study.

Malignant teratoma of the testicle: diagnosis suggested by preoperative ultrasonography.

A 22-year-old white man was found to have malignant teratoma of the testicle (nonseminomatous germ cell testicular tumor), which had been suggested by ultrasonography. Modified template retroperitoneal lymphadenectomy with nerve sparing showed no microscopic metastatic tumor.

Bile duct-specific lectins, Dolichos biflorus agglutinin and peanut agglutinin, as probes in mouse hepatocarcinogenesis.

BACKGROUND: It is well established that alterations in the expression of cell surface glycoproteins occur during the course of tumorigenesis and can be detected immunohistochemically. However, no consistent markers of malignancy in mouse hepatocellular tumors have yet been identified. EXPERIMENTAL DESIGN: Lectin histochemistry, using three bile duct-specific lectins, Dolichos biflorus agglutinin (DBA), peanut agglutinin (PNA) and soybean agglutinin (SBA), and anti-epidermal keratin immunohistochemistry, was conducted on formalin-fixed, paraffin-embedded tissues of a spectrum of benign and malignant hepatocellular proliferative lesions of mice, including hepatocholangiocarcinomas. DBA- and PNA-binding glycoproteins in normal livers and in bile and liver tumors of mice were verified by SDS-PAGE and Western blot analysis. RESULTS: Normal bile duct cells stained strongly with DBA but minimally to moderately with PNA and SBA. DBA-positive tumor cells were present in 96% of hepatocholangiocarcinomas, 89% of hepatocellular carcinomas, and 35% of hepatocellular adenomas. In comparison, 43% of hepatocholangiocarcinomas, 37% of hepatocellular carcinomas, and 24% of hepatocellular adenomas exhibited PNA staining. SBA did not specifically stain tumor cells. Normal hepatocytes and those in altered foci were consistently negative for these three lectins. Keratin-positive staining was found only in normal bile ductular cells and ductal elements in 70% of hepatocholangiocarcinomas. Electrophoresis and Western blot analysis demonstrated that, in normal livers, DBA and PNA bound to the 13- to 16-kDa and 27- to 30-kDa glycoproteins believed to be of bile duct cell origin and commonly present in hepatocellular adenomas, hepatocellular carcinomas, and hepatocholangiocarcinomas, with strongest expression in the last. In addition, hepatocholangiocarcinomas had the same high molecular mass glycoprotein (> 200 kDa) labeled with DBA as detected in bile. CONCLUSIONS: Our results suggest that some malignant hepatocytes, especially in mouse hepatocholangiocarcinomas, have the potential of biliary differentiation. DBA is a sensitive marker for malignant hepatocytes in mice.

Glucocorticoid stimulation of fatty-acid synthase gene transcription in fetal lung: antagonism by retinoic acid.

Glucocorticoid hormones are known to stimulate the rate of fatty acid biosynthesis and to increase the activity and mRNA level of fatty-acid synthase (FAS) in late gestation fetal lung. We have now examined the effect of dexamethasone on FAS transcription in fetal rat lung. Explants of 19-day fetal rat lung cultured for 48 h in serum-free medium were exposed to dexamethasone (10(-7) M) for various time periods. Nuclei were isolated, and the rate of [32P]UTP incorporation into FAS and gamma-actin RNA transcripts was measured by transcription-elongation assay. Dexamethasone increased FAS transcription but had no effect on that of actin. The maximum effect of the hormone, approximately threefold increase, was observed 1-2 h after addition of the hormone but was still apparent up to 48 h. FAS transcription but not that of actin was inhibited by cycloheximide and puromycin in both control and dexamethasone-treated cultures. However, the stimulatory effect of the hormone was not significantly reduced by the inhibitors. Retinoic acid antagonized the stimulatory effects of dexamethasone on FAS activity, mRNA content as measured by Northern analysis, mass as measured by Western blotting, and rate of transcription. The effect of retinoic acid was dependent on concentration in the relatively narrow range of 5 x 10(-6) to 5 x 10(-4) M. These data show that glucocorticoids stimulate transcription of the FAS gene in late gestation fetal rat lung, that normal transcription of the FAS gene is dependent on ongoing protein synthesis, and that glucocorticoid stimulation of FAS gene expression is antagonized by retinoic acid.

Cervical cancer radiation injury to the urinary bladder and ureters: management by cecal augmentation to a previous ileal augmentation cystoplasty.

A case report of the management of severe post cervical carcinoma pelvic radiation injuries is presented. Management was accomplished by detubularized ileal augmentation cystoplasty followed by cecal augmentation to the detubularized ileal augmentation 4 years later when bilateral ureteral obstruction developed. The development of a vesicouterine fistula required the creation of a large bowel cecal conduit for cutaneous urinary diversion utilizing the cecal augmentation antireflux segment.

Transurethral insertion of a vaginal contraceptive suppository into the urinary bladder.

PIP: Patients usually come to the emergency room within 2 hours of accidentally inserting a vaginal contraceptive suppository into the urinary bladder. Usually, there is a history of intoxication of the patient associated with the misplacement of the suppository. The patient complains of severe urgency, stranguria, intensive suprapubic pain, and hematuria. The pH of the spermicide is 3.35. For Conceptrol, the pH of the vaginal suppository is 4.5. The acidic nature of the suppositories contributes directly to the severe chemical cystitis encountered. Physical examination may reveal marked urethral edema and urethral pain. Urological evaluation demonstrates a marked reduction in the capacity of the urinary bladder with uninhibited bladder contractions. These patients have a severe hemorrhagic cystitis with pseudopolyp formation and marked elevation of the mucosal surfaces of the urinary bladder. A 3-way catheter should be inserted into the urinary bladder, and the bladder emptied. Irrigation with an alkaline solution should be initiated because of the acidic nature of the suppositories to assist in the reduction of the symptoms and duration of the chemical cystitis. Broad spectrum antibiotic coverage should be instituted along with antispasmodic therapy for the uninhibited bladder contractions. The use of intravenous steroids at high doses is recommended. The patient should be hospitalized, and an oral steroid tapering dose with prednisone should be started. Urological evaluation should be performed because of submucosal bladder hemorrhage and blood clot formation in the bladder. Significant hemorrhage from the bladder and possibly permanent bladder damage can occur. Because a significant absorption of the nonoxynol-9 can occur via the bladder mucosa, appropriate liver and renal function studies should be obtained for the treatment of the patient. There was a significant reduction in the capacity of the urinary bladder reported in some cases of nonoxynol-9 suppository insertion that persisted for up to 6 weeks.^ieng

Confocal laser scanning immunofluorescence microscopy of the pulmonary surfactant system. Association of surfactant protein A with the nucleus of the alveolar type II cell.

BACKGROUND: Localization of surfactant protein A (SP-A) to nucleus of type II cells isolated from the lungs of rats has been reported. Data suggested that most SP-A was located within lamellar bodies of the type II cell; however, some SP-A was found in other cytoplasmic regions of the cell and in particular in the nucleus. EXPERIMENTAL DESIGN: Type II cells and type II cell nuclei isolated from the lungs of rats were reacted with affinity-purified antibodies against SP-A. Location of SP-A was determined by using fluorescein isothiocyanate-labeled secondary antibodies and the distribution of fluorescence examined by using a laser scanning microscope fitted with a confocal aperture. Two-dimensional electrophoresis followed by Western blotting was used to separate and identify type II cell nuclear proteins. RESULTS: Nuclei were isolated from type II cells obtained from elastase-digested rat lungs and examined for the presence of SP-A. The nuclei contained both focal and diffuse deposits of SP-A. Some regions within the nuclear matrix (in particular the nucleolus) appeared to be relatively devoid of SP-A. The perinuclear membrane stained intensely for SP-A where optical sectioning showed its presence as a patchwork of punctate deposits. Analysis of the SP-A associated with the nucleus by two-dimensional electrophoresis revealed that it consisted of a family of proteins with molecular masses of 26, 32, and 36 kDa and pI 5.1. Biosynthesis of nuclear SP-A in primary cultures of type II cells was sensitive to inhibitors of glycosylation resulting in the presence of only the lowest molecular weight unprocessed form. CONCLUSIONS: These data indicate that three basic forms of SP-A are associated with the nucleus of the type II cell and are especially concentrated on the perinuclear membrane.

Severe chemical cystitis from the transurethral intravesical insertion of a vaginal contraceptive suppository: a report of 3 cases and proposed method of management.

We report on 3 patients who sustained severe chemical cystitis from the inadvertent insertion of a nonoxynol-9 containing vaginal contraceptive suppository into the bladder. A suggested treatment schedule is presented and the toxicity of nonoxynol-9 is discussed.

PIP: Case reports are presented on 3 patients who sustained severe chemical cystitis from the inadvertent insertion of a nonoxynol-9-containing vaginal contraceptive suppository into the bladder. A treatment schedule is suggested, and the toxicity of nonoxynol-9 is discussed. In Case 1, a 23-year-old woman had marked urinary urgency following inadvertent insertion of a vaginal contraceptive suppository into the bladder via the urethra. Emergency cystoscopy revealed severe chemical hemorrhagic cystitis with pain. The bladder was irrigated copiously with saline, and 50 cc 1% lidocaine, 100 mg hydrocortisone, and dimethyl sulfoxide were instilled intravesically. The substance in the suppository was a detergent, thus no specific treatment was performed. In case 2, a 22-year-old woman was hospitalized for severe symptoms of urgency, marked dysuria, and severe burning pain following inadvertent insertion of a vaginal suppository into the bladder. A 3-way Foley catheter was inserted, and oxybutynin and ciprofloxacin therapy was initiated. Bladder irrigations were begun with normal saline. She received 100 mg hydrocortisone intravenously every 8 hours. Cystoscopy revealed diffuse severe hemorrhagic cystitis. Retrograde cystography with the patient under anesthesia demonstrated a bladder capacity of only 300 cc. The patient had severe bladder spasms for approximately 1 month after initial insertion of the vaginal suppository. A serious fixed drug eruption developed in the right leg secondary to the nonoxynol-9. In case 3, a 26-year-old woman presented to a urology clinic 36 hours after transurethral insertion of a vaginal suppository into the bladder. Cystoscopy revealed severe hemorrhagic cystitis. The patient was treated with 1 tablet of trimethoprim-sulfamethoxazole twice a day and 5 mg oral oxybutynin every 6 hours. Significant irritation was reported using latex condoms lubricated with nonoxynol-9. The absorption of the drug via the bladder wall occurs rapidly and reaches high concentrations.

Unilateral seminal vesicle cyst presenting as hematospermia; diagnosis established by transrectal prostatic ultrasound.

A case report of a unilateral seminal vesicle cyst presenting as painless hematospermia in a 44-year-old patient is presented. Ultrasound-guided needle aspiration of the cyst demonstrated a markedly elevated LDH level in the cyst fluid of unknown significance. Antibiotic injection under ultrasound guidance into the seminal vesicle cyst was accomplished. Laboratory evaluation on the cyst fluid is suggested.

Confocal laser scanning immunofluorescence microscopy of lamellar bodies and pulmonary surfactant protein A in isolated alveolar type II cells.

We have determined the distribution of surfactant protein A (SP-A) in isolated type II cells from the lungs of rats by using immunofluorescence in conjunction with a laser scanning microscope fitted with a confocal aperture. Because of the very narrow depth of field of this microscope (less than 0.4 microns) in the confocal format, we were able to optically section type II cells and determine both the distribution of SP-A in the type II cell and the distribution of the lamellar bodies. The location of SP-A was determined by using fluorescein isothiocyanate-labeled secondary antibodies and the lamellar body distribution by using the lipid soluble fluorescent stain Phosphine 3R. SP-A was detected in the cytoplasm of type II cells as asymmetrically distributed punctate fluorescent bodies that resembled lamellar bodies in terms of size, number, and distribution within the cytoplasm of the cell. Most of the SP-A was located within bodies of the type II cell. Diffuse patches of fluorescence were seen in other cytoplasmic regions as well as the number of the cell. We conclude that SP-A is localized primarily, but not exclusively, in lamellar bodies of type II cells and that laser scanning microscopy is a much superior technique for the localization of SP-A than conventional microscopy in terms of both sensitivity and resolution.