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Chronic synovitis with marked infiltration of granulocytes in a patient with an unusual development of systemic lupus erythematosus.

The case described concerns a patient initially presenting the clinical symptoms of rheumatoid arthritis, including the presence of nodules, and slowly developing into systemic lupus erythematosus (SLE). Besides the signs of chronic inflammation in the synovial tissue, many granulocytes and PAS-positive macrophages were present. At electronmicroscopy the basal membranes of the vessels were multilaminated and the endothelial cells enlarged while many macrophages contained large clumps of electrondense material which could easily be interpreted as rough endoplasmatic reticulum (RER) of plasma cells. Immunoflourescence studies showed deposition of immunoglobulins and complement in the vessel walls of the synovium, thus suggesting an immune-complex pathogenesis.

Arthritis, Rheumatoid↗

[Development of computer-aided diagnostic system for detection of lung nodules in three-dimensional computed tomography images].

We have developed an automated computerized method for the detection of lung nodules in three-dimensional (3D) computed tomography (CT) images obtained by helical CT. In this scheme, a lung segmentation technique for the determination of the nodule search area is performed based on a gray-level thresholding technique. To enhance lung nodules, we employed the 3D cross-correlation method by using a 3D Gaussian template with zero-surrounding as a model of lung nodule. False positives are then eliminated by using a rule-base with 53 features. For further reduction of false positives, we performed linear discriminant analysis using these 53 features. The average number of false positives was 6.7 per case at a percent sensitivity of 85.0%. This computerized scheme will be useful to radiologists by providing a "second opinion" in case of possible early lung cancer.

Diagnosis, Computer-Assisted↗

No enhancement by phenobarbital of the hepatocarcinogenicity of a choline-devoid diet in the rat.

An experiment was performed to test whether inclusion of phenobarbital in a choline-devoid diet would increase the hepatocarcinogenicity of the diet. Groups of 5-week old male Fischer-344 rats were fed for 7-25 months semipurified choline-devoid or choline-supplemented diets, containing or not 0.06% phenobarbital. No hepatic preneoplastic nodules or hepatocellular carcinomas developed in rats fed the plain choline-supplemented diet, while one preneoplastic nodule and one hepatocellular carcinoma developed in two rats fed the same diet containing phenobarbital. The incidence of preneoplastic nodules and of hepatocellular carcinomas was 10% and 37%, respectively, in rats fed the plain choline-devoid diet, and 17% and 30%, in rats fed the phenobarbital-containing choline-devoid diet. The results evinced no enhancement of the hepatocarcinogenicity of the choline-devoid diet by phenobarbital. Sporadic neoplastic lesions were observed in organs other than the liver of some of the animals, irrespective of the diet fed.

Animals↗

Sequential hepatic histologic and histochemical changes produced by diethylnitrosamine in the rhesus monkey.

Six young adult male rhesus monkeys were given diethylnitrosamine ip for 3-5 years. Liver biospies were done monthly. After 6 months, biopsy specimens showed individual hepatocytes and small foci of hepatocytes that were intensely positive for glycogen. During the second and later years, larger foci of such cells developed. In sections stained with hematoxylin and eosin, the glycogen-containing hepatocytes generally appeared unusually clear. Some hepatocytes, however, had eosinophilic or basophilic cytoplasm. Nuclear enlargement and atypic developed, particularly outside the foci. The hepatocytes within most foci were uniform in their histochemical features: glycogen was elevated, glucose-6-phosphatase was decreased, and ATPase activity was present not only along the bile canalicular surface but also along the enire cell membrane. After 3-5 years, neoplastic nodules and hepatocarcinomas developed in 5 of 6 animals. Two nodules and particularly the heptocarcinomas differed from the foci in one of more histochemical parameters. The findings suggested that the glycogen-containing, histochemically altered cells of the foci in one or more histochemical parameters. The findings suggested that the glycogen-containing, histochemically altered cells of the foci may be the first step in the development of neoplasia; further steps toward malignancy appeared to be frequently associated with additional alterations, such as loss of sinusoidal ATPase and re-formation of glucose-6-phosphatase.

Adenosine Triphosphatases↗

Inhibition of promotion and persistent nodule growth by S-adenosyl-L-methionine in rat liver carcinogenesis: role of remodeling and apoptosis.

The resistant hepatocyte model (initiation/selection) and the triphasic model (initiation/selection followed by phenobarbital, for a maximum of 16 weeks) were compared for their ability to generate enzyme-altered foci (EAF) and nodules in the liver of Wistar rats initiated by diethylnitrosamine. The effects of S-adenosyl-L-methionine (SAM) on the development of preneoplastic tissue was tested in these experimental models. In the absence of phenobarbital (PB), EAF and early nodules (EN) went through a phase of rapid growth, between 4 and 9 weeks after initiation, to a phase in which progressive decrease in number and size occurred. By the 26th week only a few remodeling EAF and nodules were found. In PB-treated rats a rapid increase in the percentage of liver occupied by EAF and EN, up to the 9th week after initiation, was followed by a period of slow growth (from the 9th to the 20th week) and then, after PB withdrawal (20th week), by a drop in the number and size of EAF and EN. However, at the 26th week actively growing nodules with a low tendency to spontaneous remodeling (persistent nodules) developed. EAF and EN showed a high DNA synthesis 5 weeks after initiation. Thereafter, progressive decline in DNA synthesis, coupled with remodeling and decrease in number of biochemical markers, was seen both in the absence and, even though to a lesser extent, in the presence of PB, indicating that preneoplastic lesions became increasingly insensitive to PB. Relatively few apoptotic bodies could be observed in EAF and EN during PB treatment. After PB withdrawal, decrease in growth potential was coupled with increase in apoptotic bodies. In contrast, in persistent nodules relatively high apoptosis occurred which partially counterbalanced high DNA synthesis. Administration of SAM for a maximum of 16 weeks, starting at the 4th week after initiation, caused a great decrease in number and size of EAF and EN, associated with inhibition of DNA synthesis, high cell death by apoptosis, high remodeling, and loss of biochemical markers, in preneoplastic lesions of both PB-treated and untreated rats. A 1-8-week SAM treatment, started after the development of persistent nodules, caused a great regression of nodular lesions, coupled with a sharp fall in DNA synthesis and increase in apoptosis. It is suggested that inhibition by SAM of the development of preneoplastic tissue is linked to a shift of the equilibrium between cell production and cell death in favor of cell death.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗

Hemochromatotic arthropathy mimicking rheumatoid arthritis. A case with subcutaneous nodules, tenosynovitis, and bursitis.

A 63-year-old man developed symmetrical polyarthritis, subcutaneous nodules at the elbows, olecranon bursitis, and recurrent tenosynovitis. He was later discovered to have idiopathic hemochromatosis. Staining of the subcutaneous nodule revealed iron deposits. These manifestations which are common to rheumatoid arthritis may be seen in hemochromatotic arthropathy.

Arthritis↗

Subcutaneous Whipple's disease.

Cutaneous findings in Whipple's disease are rare and often exhibit nonspecific lesions such as hyperpigmentation, subcutaneous nodules, and erythema nodosum. A 37-year-old black man with previously documented Whipple's disease developed soft, subcutaneous nodules on the chin, neck and extremities. Biopsy of these nodules showed a nonspecific panniculitis and intracellular inclusions stained by periodic acid-Schiff reagent. The inclusions were of the type thought characteristic of Whipple's disease. These findings indicate that patients with Whipple's disease can have characteristic skin findings that can be documented by skin biopsy.

Adult↗

Nitrogen assimilation in alfalfa: isolation and characterization of an asparagine synthetase gene showing enhanced expression in root nodules and dark-adapted leaves.

Asparagine, the primary assimilation product from N2 fixation in temperate legumes and the predominant nitrogen transport product in many plant species, is synthesized via asparagine synthetase (AS; EC 6.3.5.4). Here, we report the isolation and characterization of a cDNA and a gene encoding the nodule-enhanced form of AS from alfalfa. The AS gene is comprised of 13 exons separated by 12 introns. The 5' flanking region of the AS gene confers nodule-enhanced reporter gene activity in transformed alfalfa. This region also confers enhanced reporter gene activity in dark-treated leaves. These results indicate that the 5' upstream region of the AS gene contains elements that affect expression in root nodules and leaves. Both AS mRNA and enzyme activity increased approximately 10- to 20-fold during the development of effective nodules. Ineffective nodules have strikingly reduced amounts of AS transcript. Alfalfa leaves have quite low levels of AS mRNA and protein; however, exposure to darkness resulted in a considerable increase in both. In situ hybridization with effective nodules and beta-glucuronidase staining of nodules from transgenic plants showed that AS is expressed in both infected and uninfected cells of the nodule symbiotic zone and in the nodule parenchyma. RNA gel blot analysis and in situ hybridization results are consistent with the hypothesis that initial AS expression in nodules is independent of nitrogenase activity.

Adaptation, Physiological↗

Pneumocystis carinii pneumonia presenting as cavitating and noncavitating solitary pulmonary nodules in patients with the acquired immunodeficiency syndrome.

Among 150 cases of microscopically proved Pneumocystis carinii pneumonia secondary to the acquired immunodeficiency syndrome (AIDS) seen by our pulmonary service from January 1982 to January 1986, P. carinii presented roentgenographically as a solitary pulmonary nodule in 2 patients (1.3%). It was the sole cause of the nodules as determined by clinical and roentgenographic response to specific drug therapy, examination of specimens obtained at fiberoptic bronchoscopy, and examination of lung specimens obtained at autopsy. In one of the patients, the nodule appeared to develop a large central cavity, which was confirmed at autopsy. In patients with AIDS, a solitary pulmonary nodule with or without cavitation may rarely represent P. carinii pneumonia.

Acquired Immunodeficiency Syndrome↗

Costimulation of adenylyl cyclase and phospholipase C by a mutant alpha 1B-adrenergic receptor transgene promotes malignant transformation of thyroid follicular cells.

Proliferation of thyroid follicular cells is controlled by three intra-cellular cascades [cAMP, inositol 1,4,5-triphosphate (IP3)/Ca2+/diacylglycerol (DAG), and tyrosine kinases] that are activated by distinct extracellular signals and receptors. We had previously generated a transgenic mouse model in which the cAMP cascade was permanently stimulated in thyroid cells by an adenosine A2a receptor (Tg-A2aR model). In the present work, we have generated a transgenic model characterized by the chronic stimulation of both adenylyl cyclase and phospholipase C in thyroid follicular cells. The bovine thyroglobulin gene promoter was used to direct the expression of a constitutively active mutant of the alpha 1B adrenergic receptor, which is known to couple to both cascades in transfected cell lines. The expression of the transgene resulted, as expected, in the activation of phospholipase C and adenylyl cyclase, as demonstrated by the direct measurement of IP3 and cAMP in thyroid tissue. The phenotype resulting from this dual stimulation included growth stimulation, hyperfunction, cell degeneracy attributed to the overproduction of free radicals, and the development of malignant nodules invading the capsule, muscles, and blood vessels. Differentiated metastases were found occasionally in old animals. The development of malignant lesions was more frequent and of earlier onset than in our previous Tg-A2aR model, in which only the cAMP cascade was stimulated. These observations demonstrate that the cAMP and IP3/Ca2+/DAG cascades can cooperate in vivo toward the development of thyroid follicular cell malignancies.

Adenylyl Cyclases↗

[Malignant melanoma and melanosis of the conjunctiva. Limited surgical excision and cryotherapy].

A 92 year old woman was noted to have three black conjunctival nodules and a black-brown pigmentation of the temporal conjunctiva. Extensive diffuse intraepithelial conjunctival melanomar was developed with invasive nodules. We treated this disease by judicious excision of the invasive nodules combined with cryotherapy delivered to the surrounding flat intraepithelial areas of involvement.

Aged↗

Correlation of endogenous free polyamine levels with root nodule senescence in different genotypes in Vigna mungo L.

Endogenous free polyamines, nitrogenase (EC 1.1.8.6.1, acetylene reduction), and leghaemoglobin (pyridine-hemochrome assay) levels were compared among five genotypes of developing Vigna root nodules grown under field conditions. Nitrogenase activity and leghaemoglobin level attained a peak at the flowering stage and gradually declined thereafter. Individual and total polyamine also followed the same pattern. Ranking on the basis of legume yield and other morphometric attributes was PDU-2 > UH-28 > UH-82 > T-9 > Sardhomash. Except spermine, the levels of putrescine, spermidine, and total polyamine showed significant differences (p<0.05) amongst the genotypes, particularly from flowering to mid-pod development stage. Genotype, development stage, and their interaction between the two had significant (p<0.01) effects on individual as well as total polyamines. Moreover, significant high linear correlations were found between total free polyamine and putrescine with conventional nodule senescence marker like nitrogenase (R2 = 0.94 and R2 = 0.92, respectively). Putrescine had an overall positive correlation with high legume yield. The results strongly suggest a relationship between polyamine and nodule senescence. Endogenous free polyamine and putrescine may be considered as genotypic markers for nodule senescence in field grown V. mungo. It is suggested that the flowering stage is more suitable for selection.

Fabaceae↗

Investigation of new psychophysical measures for evaluation of similar images on thoracic computed tomography for distinction between benign and malignant nodules.

We have been developing a computerized scheme to assist radiologists in improving the diagnostic accuracy for lung cancers on low-dose computed tomography (LDCT) scans by use of similar images for malignant nodules and benign nodules. A database of 415 LDCT scans including 73 cases with 76 confirmed cancers and 342 cases with 413 confirmed benign nodules was first collected in an LDCT screening program for early detection of lung cancers in Nagano, Japan. An observer study by use of receiver operating characteristics analysis was first conducted with five radiologists to demonstrate that presenting similar images for malignant nodules and benign nodules can significantly improve radiologists' performance in the diagnosis of unknown nodules. Another observer study was then conducted for obtaining reliable data on subjective similarity ratings by 10 radiologists. Based on the subjective similarity ratings, three important features were selected from a number of nodule features, and four different techniques for the determination of similarity measures, namely, a feature-based technique, a pixel-value-difference based technique, a cross-correlation-based technique, and a neural-network-based technique, were investigated and evaluated in terms of the correlation coefficient with the subjective similarity ratings. The experimental results in this study indicated that the neural-network-based technique can provide a reliable psychophysical similarity measure which is comparable to the subjective similarity ratings for a single radiologist when evaluated by use of correlation with the average similarity ratings for the other nine radiologists.

Humans↗

Transforming growth factor alpha- and c-myc-induced mammary carcinogenesis in transgenic mice.

The growth factor transforming growth factor alpha (TGFalpha) and the nuclear transcription factor c-myc often are overexpressed by human breast cancer cells. To produce models of breast disease with these etiologies, mice were generated that carried TGF-alpha- or c-myc-encoding transgenes. Transgene targeting employed the whey acidic protein (WAP) gene promoter, which is expressed in pregnant and lactating mammary epithelial cells. Non-virgin WAP-TGFalpha transgenic mice displayed accelerated mammary development during pregnancy, delayed post-parturient mammary involution, a progressive increase in the number of hyperplastic alveolar nodules (HANs), and development of mammary carcinoma with a mean latency of 9 months. Non-virgin WAP-c-myc transgenic mice displayed accelerated mammary gland development during pregnancy and development of mammary carcinomas with a latency of 8 months. Bitransgenic mice carrying both WAP-TGFalpha and WAP-c-myc displayed a dramatic acceleration of tumor development. These models identify the overexpression of TGFalpha or c-myc as etiological factors in the development of mammary neoplasia and demonstrate the increased severity of disease when both molecular alterations are present in the same cell.

Animals↗

Synchronous hepatocellular carcinoma and cholangiocarcinoma arising in two different dysplastic nodules.

We present the first reported case of explant cirrhotic liver that had synchronous cholangiocarcinoma and hepatocellular carcinoma arising in two different high-grade dysplastic nodules. The patient was a 55-year-old woman who had hepatitis B virus-associated liver cirrhosis for 3 years. The moderately differentiated cholangiocarcinoma occurred in high-grade dysplastic nodule with a 1.7-fold cell density compared with that of cirrhotic nodule. The hepatocellular carcinoma arose in a nodule-in-nodule pattern within a peripherally low-grade and centrally high-grade dysplastic nodule and had a 2.7-fold cell density compared with that of cirrhotic nodule. By immunohistochemistry, the tumor cells of the cholangiocarcinoma as well as bile ductular cells in dysplastic nodule were diffusely positive for cytokeratin 7, whereas hepatocellular carcinoma cells and dysplastic hepatocytes were negative for cytokeratin 7. The c-kit-positive hepatic progenitor cells were singly scattered between hepatocytes, and their number was highest in cirrhotic nodule and decreased in dysplastic nodule, whereas they were absent in cholangiocarcinoma and hepatocellular carcinoma arising in dysplastic nodules. Proliferation indices were progressively increased in cirrhotic nodule, dysplastic nodule, and cholangiocarcinoma or hepatocellular carcinoma, sequentially. These observations indicate that cholangiocarcinoma as well as hepatocellular carcinoma can develop in dysplastic nodule and that hepatic progenitor cells might play a role in the early stage of cholangiocarcinogenesis and hepatocarcinogenesis.

Bile Duct Neoplasms↗

Keratoacanthoma developing in prurigo nodularis treated with cryotherapy.

We describe an elderly woman in whom keratoacanthoma developed from one nodule of prurigo nodularis that had been treated with cryotherapy for 3 months. Since in our case keratoacanthoma developed after treatment with liquid nitrogen for prurigo nodularis which had been constantly scratched in the past, we hypothesize that irritations of cryotherapy in addition to repeated mechanical traumas of scratching might have played a role in the formation of this tumor.

Aged↗

Papillary carcinoma of the thyroid occurring during pregnancy. Report of a case diagnosed by fine needle aspiration cytology.

A case of papillary carcinoma of the thyroid gland occurring during pregnancy in a 29-year-old woman is described. The enlarged thyroid nodule was first detected at 10 weeks of gestation; fine needle aspiration (FNA) of the nodule showed no cytologic evidence of malignancy. Repeat FNA at 30 weeks of gestation produced inadequate material for diagnosis. A final FNA at 38 weeks of gestation showed classic cytologic features of papillary carcinoma, including papillary structures, grooved nuclei and intranuclear cytoplasmic inclusions. After delivery, the patient was treated with total thyroidectomy and cervical lymph node dissection. The enlargement of the nodule in this case during the course of the pregnancy suggests a relationship between pregnancy and the malignant development of thyroid nodules; this is discussed along with the utility of FNA cytology for diagnosing thyroid cancers during pregnancy.

Adult↗

Nodule-specific repression of yellow lupin protein R18.

It was found, using immunochemical techniques, that protein R18 presumably specifically repressed during development of lupin root nodules (Sikorski et al., 1989, Acta Biochim. Polon., 36, 63-72) is present in various tissues of this plant. Protein R18 was also detected in roots of four other legumes but was absent from the bacteroid-containing cells of root nodules. The data support our earlier view (Sikorski et al., op. cit.) that expression of protein R18 is regulated by the coupled mechanism of induction and repression of specific plant genes during development of lupin root nodule.

Fabaceae↗