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A 7-year-old female Kerry blue terrier dog developed 20 cutaneous nodules, up to 4 mm in diameter, over the body. Light and electron microscopy demonstrated that they were virus-associated inverted papillomas and they are described because canine skin viral papillomas have not been frequently reported.
Advances in molecular biology research continue to have a major impact on clinical medicine. These advances have provided a means to produce proteins previously available in limited supply and allow for the production of novel proteins that are improved agonists or else antagonists with greater specificity for therapeutic targets. Newer drug delivery systems should facilitate delivery of these proteins. By combining the capabilities to produce drug targets in acceptable quantities with improved methods for determining the three-dimensional structures of these targets, novel organic therapeutic molecules that act on these targets will be designed. Gene transfer therapy using genes that express important proteins or that encode "antisense" RNAs that inhibit the translation of specific mRNAs will soon become a reality. The use of RFLPs and PCR methodologies promises increased means to diagnose specific genetic diseases and infections. Most importantly, molecular biology is helping to understand the mechanisms of disease such that novel diagnostic and therapeutic approaches can be described. These advances are providing an understanding of the mechanisms involved in cancers of the thyroid gland. They have already led to an enhanced understanding of (1) the growth factors that control proliferation of the thyroid gland, (2) the potential steps in thyroid nodule and neoplasia development, (3) particular mutations that may occur as thyroid cancers develop, (4) oncogenes that are expressed in thyroid cancers, and (5) the genetic defects that are responsible for thyroid gland malignancies in the multiple endocrine neoplasia (MEN) syndromes. With the latter, the RFLP technology has already provided an enhanced means to diagnose the disorder. With further progress, enhanced means for diagnosis and treatment should emerge. Molecular biology techniques are contributing to an increased understanding of the mechanisms of development of autoimmune thyroid disease as with Graves' disease and Hashimoto's thyroiditis. The potential role of infections, histocompatibility antigens, thyroid gland and extraglandular antigens, immune modulators, subpopulations of T-cells such as suppressor and helper cells, other cells involved in immune responses, and a combination of influences of several different functions on the thyroid gland are being defined. This knowledge should soon suggest improved means for diagnosis and treatment. Understanding of the function of the thyroid hormone receptors should have clinical importance. This knowledge suggests a means to develop thyroid hormone antagonists that may be used to more rapidly ameliorate the effects of hyperthyroidism and could be useful in nonthyroidal disorders such as cardiac arrhythmias.(ABSTRACT TRUNCATED AT 400 WORDS)
We report a case of epithelioid hemangioendothelioma observed in soft tissue in a 35-year-old man who presented a painful mass of the right arm which progressed in size for two years. Imaging revealed a 7-cm poorly limited expansive tumor process located in the medial muscle compartment of the right arm. Surgical resection was performed. Histological and immunohistochemical examination led to the diagnosis of soft tissue epithelioid hemangioendothelioma. The tumor recurred in the right arm and the right axillary fossa with development of multiple nodules in the contralateral thoracic wall and pleural effusion. Adjuvant chemotherapy and radiotherapy were performed, but the patient died at two years.
In a double-blind trial on 37 asymptomatic microfilaraemic subjects (minimum 400 microfilariae [mf] per mL) with Wuchereria bancrofti infection, the safety, tolerability and macrofilaricidal efficacy of 12 fortnightly doses of ivermectin, 400 micrograms/kg (ivermectin group), was compared with 12 fortnightly doses of diethylcarbamazine (DEC), 10 mg/kg (DEC group), over a period of 129 weeks after treatment. A control group (LDIC group) was treated with low dose ivermectin to clear microfilaraemia, for ethical reasons. Both ivermectin and DEC in high multiple doses were well tolerated and clinically safe. Macrofilaricidal efficacy was assessed by prolonged clearance of microfilaraemia, appearance of local lesions, and reduction of circulating W. bancrofti adult antigen detected by an antigen capture enzyme-linked immunoassay based on the monoclonal antibody AD12. Mf counts fell more rapidly after ivermectin than after DEC, but low residual mf levels were equivalent in these groups after week 4. Conversely, filarial antigen levels fell more rapidly after DEC than after ivermectin, but low residual antigen levels in these groups were statistically equivalent at all times beyond 12 weeks. Mild, self-limited systemic reactions to therapy were observed in all 3 treatment groups. Local reactions, such as development of scrotal nodules, were observed in several subjects in the DEC and ivermectin groups. These results suggested that high dose ivermectin and DEC both had significant macrofilaricidal activity against W. bancrofti, but neither of these intensive therapeutic regimens consistently produced complete cures. Thus, new drugs or dosing schedules are needed to achieve the goal of killing all filarial parasites in the majority of patients.
The incidence of autoimmune disease of the thyroid approaches 10% in women. This autoimmune state, which predisposes to the development of thyroid neoplasia, especially in patients with subclinical hypothyroidism, combined with tumor growth and immunologic factors that occur in the pregnant state, account for the significant incidence of nodular thyroid disease in pregnancy. Thyroid carcinoma of follicular cell origin in a young woman can generally be expected to pursue a slow course with ample time for preoperative preparation and operative treatment. However, the pregnant state should be considered an exception and thyroid nodular disease with suspicious aspiration cytologic features should be managed with a certain degree of urgency. In an excellent article on the subject of pregnancy as a predisposing factor in thyroid neoplasia, Rosen and Walfish present a series of 30 patients with thyroid neoplasia arising during pregnancy. The incidence of thyroid carcinoma was 43% and the incidence of adenoma 37%, for an 80% overall incidence of neoplasia. Furthermore, during the course of the pregnancy, 20% of the patients showed marked increase in nodular growth, including a 26-year-old primiparous woman who developed a small nodule in the first trimester which proved to be cellular on needle aspiration biopsy. In spite of thyroid hormone treatment, the nodule grew markedly in the last trimester. At postpartum operation, the patient was found to have a papillary carcinoma with extensive unilateral neck and mediastinal node disease, which was clinically occult. These authors stress the importance of the operative treatment of thyroid neoplasia of pregnancy, either in the second trimester or immediately after delivery. We agree.
Nodular transformation, a rare hyperplastic condition of the liver, has been reported in patients with rheumatoid arthritis, Felty's syndrome, the CRST syndrome, and myeloproliferative disorders. Associated disorders in the present clinicopathologic study of 30 cases included the foregoing as well as extrahepatic neoplasms, endocrine disorders, and other diseases producing immune dysfunction; some patients had received drug therapy for a prolonged time. Clinically nodular transformation may be confused with cirrhosis; histologic evaluation of liver biopsy material is essential for diagnosis. Complications include portal hypertension, hepatic failure, and rupture of the liver. Histologic and experimental evidence suggests that nodular transformation is preneoplastic, possibly giving rise to hepatocellular adenomas or carcinomas. Experimental and clinical data suggest that drugs should be considered as possible etiologic factors in the development of the nodules.
Poly(2-hydroxyethyl methacrylate) (pHEMA) has potentially wide biomedical applications: it is biocompatible, allows immobilization of cells or bioactive molecules and has a hardness comparable to bone. We previously reported that immobilization of alkaline phosphatase (AlkP) in pHEMA can initiate mineralization in a manner that mimics the calcification of cartilage and woven bone. Because numerous proteins known to initiate mineralization possess acidic species, we have modified the neutral electrical surface of pHEMA by carboxymethylation (CM). We have studied the effects of these negative groups on the calcification process in vitro. Calibrated pellets of pHEMA were prepared and carboxymethylated by soaking with 0.5 M bromoacetic acid in 2 M NaOH. Pellets of pHEMA, pHEMA-AlkP and pHEMA-CM were incubated during 5, 10 and 15 days in two types of body fluid: normal (1X) and 1.5X concentration of ions. Nodules of hydroxyapatite developed on pHEMA-AlkP and pHEMA-CM but not on pHEMA. Hydroxyapatite crystals were dissolved in HCl allowing calcium to be dosed. CM significantly increased the amount of deposited Ca by 1.8 folds in the 1X fluid and 15.8 folds in the 1.5X fluid. The presence of AlkP considerably increased the amount of deposited Ca: 25.9 folds in 1X and 23.3 in 1.5X. ROS 17/2.8 osteoblast-like cells were seeded on the materials and examined by confocal microscopy after phalloidin staining. Cells grown on pHEMA alone appeared round, while cells grown on the crystals deposited on the pHEMA-CM or pHEMA-AlkP were flattened. The presence of AlkP favours the mineralization process more than the existence of surface negative groups on the polymer. Cells preferentially adhere to the polymer when hydroxyapatite crystals were developed.
A 31-year-old black man with a history of intravenous drug abuse developed a mass in his neck, a biopsy of which revealed Kaposi's sarcoma. The patient underwent radiation therapy, and the mass diminished in size. Approximately 2 months later the patient developed a herpes zoster infection in the left T3 distribution. The vesicular eruption resolved, but postherpetic neuralgia remained. Two months after the herpes zoster infection, the patient developed many small nodules in the area of the prior vesicular eruption. Biopsy revealed these nodules to be Kaposi's sarcoma. At this time no other cutaneous lesions were present. We believe that these nodules represent the occurrence of the Koebner phenomenon in a patient with Kaposi's sarcoma and the acquired immunodeficiency syndrome.
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been shown to induce marked atrophic changes of exocrine pancreas of rats when given at 400 ppm in diet. On the other hand, 3,2'-dimethyl-4-aminobiphenyl (DMAB) causes pancreatic acinar tumors. Both chemicals also induce intestinal tumors. In the present experiment, the possible promotional effects of PhIP on DMAB-induced carcinogenesis in the rat were investigated with particular attention given to the pancreas and intestine. After initiation with subcutaneous injections of DMAB (150 mg/kg b.w.) once a week for 3 weeks, PhIP was administered in the diet at doses of 200, 100, 25 and 0 ppm from weeks 5 to 40. In a dose-dependent manner, PhIP clearly increased the numbers of basophilic acinar foci and nodules while decreasing development of acidophilic lesions. The incidences of adenocarcinomas of the small intestine but not the colon demonstrated a tendency for an increase with the higher doses of PhIP. The results thus indicated that PhIP administration after DMAB treatment exerts two different effects on pancreatic acinar cell lesions, enhancing the growth of basophilic foci and suppressing that of their acidophilic counterparts. Any influence on alimentary canal tumorigenesis was limited to the small intestine.
This report describes a case of unusual intraductal "clear cell" changes of male breast that mimicked pagetoid ductal spread of lobular neoplasia. The lesion developed inside a nodule of gynecomastia of the left breast in a 56 year-old man. Immunohistochemically, the enlarged clear cells reacted positively with epithelial membrane antigen, low molecular weight cytokeratin and three breast markers (i.e.: gross cystic disease fluid protein-15 and -44 and estrogen receptors). They were negative for high molecular weight cytokeratin, muscle-specific actin, desmin and vimentin. Differential diagnoses included pagetoid ductal involvement by lobular neoplasia (i.e.: lobular carcinoma in situ and/or atypical lobular hyperplasia), pagetoid growth of intraductal carcinoma, atypical intraductal hyperplasia, and unusual intraductal myoepithelial proliferative lesion.
The sensitivity of elevated serum ornithine carbamyltransferase (OCT) as an index of hepatotoxicity in rats was assessed in different studies conducted over a number of years and originally designed to examine the toxicity or carcinogenicity of a variety of test chemicals and diets. Changes in serum OCT activities were compared with the more widely used clinical endpoints, alanine aminotranserase (ALT) and aspartate aminotransferase (AST). In the first study, rats received a single oral dose of the hepatotoxic and hepatocarcinogenic fungal toxin aflatoxin B(1) (AFB(1)). The increase in enzyme levels between control and AFB(1)-treated rats was greater for serum OCT than for ALT or AST. This response was similar to the changes in serum enzyme levels in studies where rats ingested a hepatotoxic and hepatocarcinogenic choline deficient (CD) diet. When rats were exposed to the hepatotoxic and nephrotoxic fungal toxin fumonisin B(1) (FB(1)) by intraperitoneal injection for 6 days, serum AST and ALT were significantly elevated above control levels while OCT was unaffected. The peroxisome proliferator ciprofibrate caused elevated ALT and AST but not OCT at week 52 of dietary exposure, after the development of liver nodules and tumours. Of the two liver-specific enzymes examined in all of the studies, ALT was more consistently predictive of hepatotoxicity than OCT.
We report two cases of body piercing as a religious practice that subsequently led to the development of granulomatous nodules at previously punctured sites of the skin and oral mucosa. These lesions were diagnosed as sarcoid-like foreign body reaction after other possible causes including sarcoidosis, tuberculosis, tuberculoid leprosy, fungal infections, viral infections, and Crohn's disease were excluded.
BACKGROUND & AIMS: Hepatic fibrosis and cirrhosis are the consequences of many types of chronic liver disease, and, at its final stage when liver nodule and scarring develop, they are generally considered to be irreversible. METHODS: Here we describe 3 patients with chronic hepatitis B with clinical, biochemical, and histologic evidence of cirrhosis. They underwent treatment with interferon-alpha or lamivudine and had follow-up liver biopsy while in clinical, biochemical, and virologic remission. Biopsy specimens were randomly coded in unpaired manner according to patient, and they were read independently by 2 pathologists using the modified hepatitis activity index (with a maximum stage of 6). The mean interval between biopsies was 5.5 years. RESULTS: The mean ALT level decreased from 113.7 to 28.3 U/L. The mean bilirubin level decreased from 2.4 to 0.9 mg/dL, and the mean prothrombin time decreased from 16.3 to 12.3 seconds. The mean Child-Pugh score decreased from 8 to 5. The mean fibrosis score decreased from 5.8 to 0.5 (P = 0.004), and the mean grading score decreased from 10.8 to 3.2 (P = 0.017). CONCLUSIONS: Cirrhosis due to chronic hepatitis B might be reversible in some patients who respond to antiviral therapy.
Cutaneous metastasis from gastric adenocarcinoma is an infrequent disease entity. When present, it typically signifies disseminated disease with a poor prognosis. We report a case of a 57-year-old male patient with gastric cancer who developed generalized erythematous nodules on the chest, abdomen, back, neck, and four extremities 2 months postoperatively. Results of a skin biopsy disclosed groups of metastatic adenocarcinoma cells in the dermis and subcutaneous tissue, forming clusters and strands in a desmoplastic stroma. Histopathologic examination demonstrated that the cutaneous metastasis was of stomach origin.
Vocal fold palsy is a cause of dysphonia. Due to incomplete glottic closure during phonation, patients with a unilateral vocal fold palsy present with a weak and breathy voice and recurrent aspiration. To lessen the clinical manifestations of unilateral vocal fold palsy, polytetrafluoroethylene (Teflon) paste is one agent which has been injected into the paraglottic region, thus causing the vocal fold to move more medially. One of the complications associated with Teflon paste injection is migration of the paste into the surrounding tissues. We present a patient with idiopathic left vocal fold palsy who underwent Teflon injection to the vocal fold and subsequently developed a precricoid nodule, mimicking a cartilaginous swelling.
RON, a member of the MET proto-oncogene family, has been implicated in the progression of certain epithelial cancers. The purpose of this study was to determine the oncogenic potential of RON in vivo in lung epithelial cells. Transgenic mice were established using surfactant protein C promoter to express human RON in the distal lung epithelial cells. These mice were born normal but developed multiple lung tumors with distinct morphology and growth patterns. Tumors appeared as a single mass in the lung around 2 months of age and gradually developed into multiple nodules located mostly in the peripheral portions of the lung. A transition from early adenomas to later adenocarcinomas was observed. Morphologically, tumors were characterized as cuboidal epithelial cells with a type II cell phenotype, grew along the alveolar walls, and projected into the alveolar septa. RON was highly expressed and constitutively activated in tumors. These results indicate that overexpression of human wild-type RON causes the formation of lung tumors with unique biological characteristics in vivo. This model provides opportunities to study the role of RON in the pathogenesis of lung tumors and to elucidate the mechanisms underlying this distinct lung tumor.
A 53-year-old woman with systemic sclerosis developed numerous cutaneous nodules, resembling keloids, on her anterior chest wall. The nodules failed to respond to therapy with topical steroid, calcipotriol, or extended photochemotherapy. This is a rare, disfiguring variant of scleroderma, unresponsive to treatment, and poorly understood.
AIMS: Comparison of molecular and antibiotic resistance profile methods to identify an easy method that can differentiate between strains of introduced Bradyrhizobium japonicum and the indigenous Bradyrhizobium spp. (TGx) isolates which nodulate the newly developed TGx soybean cultivars in Africa. METHODS AND RESULTS: Restriction fragment length polymorphism (RFLP) of 16S rDNA generated by five restriction enzymes, banding patterns in Southern hybridization using nod and nif genes as probes, and resistance patterns of the isolates to nine antibiotics, were used to group 26 Bradyrhizobium spp. (TGx) isolates and four other Bradyrhizobium strains. The clusters of isolates obtained from the four grouping methods were all different, although all methods revealed large genetic diversity among the isolates. CONCLUSIONS: Results indicate that the antibiotic resistance profile method is as good as the three molecular methods used in this study for phylogenetic grouping of the Bradyrhizobium spp. (TGx) isolates, which may serve as a basis for further characterization of selected isolates from each group. SIGNIFICANCE AND IMPACT OF THE STUDY: The antibiotic resistance profile method can be used as a simple means of assessing genetic variability and grouping of a large number of Bradyrhizobium spp. (TGx) isolates. Representative isolates from each group can then be selected for further characterization.