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Detection of hepatocellular carcinomas and dysplastic nodules in cirrhotic liver: accuracy of ultrasonography in transplant patients.

The purpose of this study was to assess the usefulness of ultrasonography in the detection of hepatocellular carcinomas and dysplastic nodules in patients with liver cirrhosis. Pretransplantation sonograms in 52 patients with liver cirrhosis who underwent orthotopic liver transplantation were evaluated retrospectively. The numbers of hepatocellular carcinomas and dysplastic nodules were assessed in the explanted liver specimens and compared with pretransplantation ultrasonographic results. Eighteen hepatocellular carcinomas in 16 patients and 20 dysplastic nodules in 11 patients were present in the explanted livers. The size of hepatocellular carcinomas ranged from 0.6 to 5.0 cm (mean, 2.1 cm) in diameter, and that of dysplastic nodules ranged from 0.5 to 1.7 cm (mean, 1.0 cm) in diameter. Pretransplantation ultrasonography enabled detection of 6 of 18 hepatocellular carcinoma and 0 of 20 dysplastic nodule lesions; lesion detection sensitivity for hepatocellular carcinomas and dysplastic nodules was 33% and 0%, respectively. Patient sensitivity and specificity for hepatocellular carcinomas were 38% (6 of 16) and 92% (33 of 36), and those for dysplastic nodules were 0% and 95% (39 of 41), respectively. On the basis of our results, ultrasonography is insensitive for detection of hepatocellular carcinomas and dysplastic nodules in patients with advanced liver cirrhosis.

Adult↗

Multiple macroregenerative nodules in liver cirrhosis due to Budd-Chiari syndrome. Case reports and review of the literature.

Clinical, radiological, histological and immunohistochemical methods were used to define the nature of multiple rapidly growing hepatic nodules in 2 young patients with Budd-Chiari syndrome due to myeloproliferative diseases. In one patient, the arterial hyperperfusion of large nodules was demonstrated by dynamic computed tomography and angiography. The explanted livers of these patients showed multiple well-demarcated nodules up to 3 cm in diameter on the background of liver cirrhosis resulting from chronic hepatic congestion. Histologically, these nodules covered a spectrum ranging from adenoma-like lesions to nodules resembling focal nodular hyperplasia. They consisted of essentially normal hepatocytes, and variably contained fibrous septa including neoductules and large, mostly dysmorphic arteries. Sometimes, they were located close to still patent or recanalized veins. These rapidly growing hepatic nodules are best defined as macroregenerative nodules. The knowledge of this entity may help the physician to avoid misinterpretation of such nodules as carcinomas.

Adolescent↗

[Ultrastructure of bacteroid-containing tissue of Pisum sativum L. peas having various regulatory mechanisms of nodulation].

The infected root nodule cells of Pisum sativum cvs. Torsdag, Rondo and its supernodulating mutant nod3 have been investigated by transmission electron microscopy and morphometrically. Torsdag and nod3 developed effective nodules, when grown with or without nitrates in the growth medium. The nodules developed by Rondo were ineffective in the presence of nitrates, and otherwise effective. An obvious similarity in the fine structure of bacteroid tissue of root nodules has been observed in Torgsdag (Nod5) and the supernodulating mutant nod3, both forms being nitrate-tolerant, but nodulation being controlled by different genetic systems. The statistical processing results showed significant differences in the respective morphometric parameters of nodule cells between the plants grown according to either scheme: with and without nitrates. Combined nitrogen is likely to affect the ratio of symbionts in the infected nodule cells of cultivars with nitrate-tolerant nodulation.

Bacteria↗

Comparison of [(18)F]FDG PET and (201)Tl SPECT in evaluation of pulmonary nodules.

UNLABELLED: Recent reports have indicated the value of [(18)F]FDG PET and (201)Tl SPECT in diagnosing lung cancer. In this study, we compared the diagnostic value of FDG PET and (201)Tl SPECT in the evaluation of pulmonary nodules. METHODS: Sixty-three patients with 66 pulmonary nodules suspected to be lung cancer on the basis of chest CT were examined by FDG PET and (201)Tl SPECT (early and delayed scans) within a week of each study. For semiquantitative analysis, the standardized uptake value (SUV) or the tumor-to-nontumor activity ratio (T/N) (or both) was calculated. All of these lesions were completely removed thoracoscopically or by thoracotomy and were examined histologically. RESULTS: Fifty-four nodules were histologically confirmed to be malignant tumors, and 12 were benign. Both techniques delineated focal lesions with an increase in tracer accumulation in 41 of 54 lung cancers. (201)Tl SPECT on early or delayed scans (or both) identified 4 additional lung cancers that FDG PET images did not reveal: 3 bronchioloalveolar carcinomas and a well-differentiated adenocarcinoma. FDG PET identified 3 additional lung cancers that (201)Tl SPECT images did not reveal; 2 of these lung cancers were <2 cm in diameter. The mean FDG SUV and T/N of bronchioloalveolar carcinomas (2.06 +/- 0.76 and 3.49 +/- 1.03, respectively) were significantly lower than those of poorly differentiated adenocarcinomas (5.55 +/- 2.01 [P = 0.026] and 8.23 +/- 2.16 [P = 0.01], respectively). However, no significant difference was found in (201)Tl T/N on early and delayed scans between bronchioloalveolar carcinomas (1.64 +/- 0.29 and 1.87 +/- 0.42, respectively) and poorly differentiated adenocarcinomas (1.58 +/- 0.32 and 2.76 +/- 1.36, respectively). Of the 12 benign nodules, FDG PET and (201)Tl SPECT showed false-positive results for the same 7 benign nodules (58.3%) (4 granulomas, 1 sarcoidosis, 1 inflammatory pseudotumor, and 1 aspergilloma). Negative FDG PET findings and positive (201)Tl SPECT findings were obtained only for bronchioloalveolar carcinomas or a well-differentiated adenocarcinoma but not for other histologic types of lung cancers or benign pulmonary nodules. CONCLUSION: No significant difference was found between FDG PET and (201)Tl SPECT in specificity for the differentiation of malignant and benign pulmonary nodules. The degree of differentiation of lung adenocarcinoma correlated with FDG uptake but not with (201)Tl uptake. Bronchioloalveolar carcinoma (a well-differentiated, slow-growing tumor) findings typically were positive with (201)Tl but were negative with FDG. The combination of FDG PET and (201)Tl SPECT may provide additional information regarding the tissue characterization of pulmonary nodules.

Adenocarcinoma↗

Molecular cloning, functional characterization, and subcellular localization of soybean nodule dihydrolipoamide reductase.

Nodule ferric leghemoglobin reductase (FLbR) and leaf dihydrolipoamide reductase (DLDH) belong to the same family of pyridine nucleotide-disulfide oxidoreductases. We report here the cloning, expression, and characterization of a second protein with FLbR activity, FLbR-2, from soybean (Glycine max) nodules. The cDNA is 1,779 bp in length and codes for a precursor protein comprising a 30-residue mitochondrial transit peptide and a 470-residue mature protein of 50 kD. The derived protein has considerable homology with soybean nodule FLbR-1 (93% identity) and pea (Pisum sativum) leaf mitochondria DLDH (89% identity). The cDNA encoding the mature protein was overexpressed in Escherichia coli. The recombinant enzyme showed Km and kcat values for ferric leghemoglobin that were very similar to those of DLDH. The transcripts of FLbR-2 were more abundant in stems and roots than in nodules and leaves. Immunoblots of nodule fractions revealed that an antibody raised against pea leaf DLDH cross-reacted with recombinant FLbR-2, native FLbR-2 of soybean nodule mitochondria, DLDH from bacteroids, and an unknown protein of approximately 70 kD localized in the nodule cytosol. Immunogold labeling was also observed in the mitochondria, cytosol, and bacteroids of soybean nodules. The similar biochemical, kinetic, and immunological properties, as well as the high amino acid sequence identity and mitochondrial localization, draw us to conclude that FLbR-2 is soybean DLDH.

Amino Acid Sequence↗

Molecular aspects of soybean cultivar-specific nodulation by Sinorhizobium fredii USDA257.

Sinorhizobium fredii USDA257 forms nitrogen-fixing nodules in association with the primitive soybean cultivar 'Peking' but fails to initiate nodules on many advanced soybean cultivars, including 'McCall'. This distinction is controlled by a set of nodulation genes termed nolXWBTUV. Inactivation of any of these genes enables USDA257 to nodulate McCall and many other improved soybean cultivars. Mutation in the nolXWBTUV locus also alters the Nod factor structure resulting in the production of a novel molecule with glucose incorporated into the chitin backbone. Some of the genes located in the nolXWBTUV locus reveal sequence homologies to known components of the type III secretion system (TTSS) of plant and animal pathogenic bacteria. Recent studies have demonstrated the presence of a complete TTSS in USDA257 and few other symbiotic bacteria. The TTSS cluster of USDA257 contains 27 open reading frames out of which 10 code for the structural components of the TTSS. USDA257, when grown in presence of flavonoids, secrete several proteins called Nops (Nodulation Outer Proteins) into the extracellular environment. Genes located in the TTSS of USDA257 encode some of the extracellular proteins, such as NopX, NopB, and NopL. These type III secreted proteins appear to play an important role in regulating nodulation in a host-dependent manner. Failure to elaborate the Nops results in a drastic phenotypic effect on soybean nodulation, indicating that these proteins may play a pivotal role in soybean cultivar specificity. The secretion of Nops appears to be facilitated by novel filamentous appendages (pili) that are produced by USDA257 upon induction by flavonoids. Biochemical studies have demonstrated the close association of several Nops with the purified pili. However, it remains to be seen if the filamentous appendages can function as conduits for delivery of Nops into the host cell. This review examines the current state of our knowledge on the molecular aspects of soybean cultivar-specific nodulation by USDA257.

Bacterial Proteins↗

Analysis of the root nodule-enhanced transcriptome in soybean.

For high throughput screening of root nodule-enhanced genes, cDNA libraries specific for three different developmental stages of soybean root nodules were constructed after inoculation with Bradyrhizobium japonicum USDA110. 5,469 cDNA clones were sequenced and grouped into 2,511 non-redundant (nr) ESTs consisting of 769 contigs and 1,742 singletons. Using similarity searches against several public databases we constructed a functional classification of the ESTs into root nodule-specific nodulin genes, stress-responsive genes and genes related to carbon and nitrogen metabolism. We also constructed a cDNA microarray with 382 selected clones that appeared to be up-regulated in the root nodule. Using the microarray we compared the transcript levels of uninfected roots and root nodules from four developmental stages. We identified 81 genes that were differentially expressed, and grouped them into seven clusters according to the similarity of their expression profiles, using a hierarchical clustering algorithm. Clusters 1, 2, 3, and 6, comprised of 58 genes, showed root nodule-enhanced expression. The information from this study will be used to analyze the roles of root nodule-specific genes and signaling pathways during root nodule development.

Databases, Nucleic Acid↗

A relative deficiency of cytochrome P-450 and aryl hydrocarbon [benzo(a)pyrene] hydroxylase in hyperplastic nodules induced by 2-acetylaminofluorene in rat liver.

The concentrations of cytochrome P-450 and the activities of aryl hydrocarbon [benzo(a)pyrene] hydroxylase (AHH) and reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase were measured in early (gray-white) and remodeled (brown) hyperplastic nodules induced in the livers of rats with 2-acetylaminofluorene and were compared to the values in control livers and in the liver surrounding the nodules. Cytochrome P-450 content of early (14 weeks) hyperplastic nodules is 30% of the activity of untreated control livers and 48% of the activity of the surrounding liver. AHH activity of the early nodules is 10% of the control activity and 33% of the activity in the surrounding nonnodular liver. Nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity in the microsomes of early nodules is 76% of the control activity and 78% of the activity in the surrounding liver. In the late remodeled nodules, (22 and 25 weeks), the cytochrome P-450 content is 40% of that of controls and AHH activity is 15% of the control activity. In primary hepatomas induced by 2-acetylaminofluorene, cytochrome P-450 content is 21% of that of controls, AHH activity is 11% of the activity of controls, and reductase is 50% of the control activity. These results, indicating a relative nodule deficiency in some of the cellular components believed to be important in the activation of hepatocarcinogens and hepatotoxins, offer one possible explanation for the relative resistance to carcinogen cytotoxicity of hyperplastic liver nodules.

2-Acetylaminofluorene↗

Regulation of microsomal, xenobiotic epoxide hydrolase messenger RNA in persistent hepatocyte nodules and hepatomas induced by chemical carcinogens.

We have utilized a DNA clone complementary to epoxide hydrolase mRNA as a probe to examine the level of the mRNA in persistent hepatocyte nodules and hepatomas induced by the Solt-Farber chemical carcinogenesis procedure. Epoxide hydrolase mRNA is increased 14-fold in nodules as compared to the level in normal liver. When rats with liver nodules were administered phenobarbital, an inducer of epoxide hydrolase mRNA in normal animals, a superinduction in epoxide hydrolase mRNA was observed in the nodules (22-fold) as compared to normal liver. Surprisingly, nodule induction in conjunction with phenobarbital administration also produced marked elevation in epoxide hydrolase mRNA levels in the tissue surrounding the nodules. Using HpaII and MspI to assess the degree of methylation of CCGG sites, we have found that the epoxide hydrolase gene is hypomethylated in nodules and hepatomas compared to the gene in normal liver tissue. Phenobarbital treatment alone increased epoxide hydrolase mRNA levels but did not result in hypomethylation of the epoxide hydrolase gene. These data further support the observation that hypomethylation of specific gene sequences occurs during chemical carcinogenesis and is correlated with an elevation in the steady state level of epoxide hydrolase mRNA in persistent hepatocyte nodules.

Animals↗

Nodular duodenitis and single duodenal nodules.

Duodenal nodules are an uncommon endoscopic finding generally thought to indicate duodenal inflammation. This study examines the incidence and histologic correlates of multiple and single duodenal nodules in 2,966 consecutive male patients who underwent esophagogastroduodenoscopy during the past five years. Five per cent had duodenal nodules. When two or more discrete nodules, with or without apical ulceration, were present, the finding was termed nodular duodenitis, which was seen five and one-half times more frequently than single nodules. There were 127 patients with nodular duodenitis (4.3%); seven had chronic renal disease and 33 (26%) had concomitant peptic ulcer disease. Biopsies showed either normal mucosa or histologic aberrations typical of nonspecific duodenitis. Single nodules were seen in only 23 patients (0.8%). Biopsies of these nodules revealed benign or malignant tumors in five instances and infrequently showed only normal mucosa. It is concluded that nodular duodenitis is a visually distinct, morphologic variant of nonspecific duodenitis bearing some yet-to-be-defined relationship to peptic ulcer disease. Single nodules are much less likely to represent duodenitis and, in fact, they have significant neoplastic potential, mandating biopsy whenever they are found.

Aged↗

Nodular alteration of the paracortical area. An in situ immunohistochemical analysis of primary, secondary, and tertiary T-nodules.

With the use of in situ immunohistochemical techniques on freshly frozen and paraffin-embedded material from 63 reactive lymph nodes, the cellular composition of T-nodules observed in 30 cases with nodular alteration of the paracortical area was analyzed. T-nodules were composed of S-100 beta + interdigitating reticulum cells (IDRCs), variable numbers of OKT6+ dendritic cells (DCs), high endothelial venules, and a very high T helper/T suppressor ratio because of an enrichment of OKT4+, Leu3a+ helper/inducer T cells in these nodules. According to their localization in the paracortical area, and the arrangement of IDRCs and high endothelial venules, T-nodules could be divided into "primary" and "secondary" T nodules. In all cases of dermatopathic lymphadenitis, very large aggregates of S-100 beta + and OKT6+ DCs, admixed with few high endothelial venules and variable numbers of OKT4+, Leu3a+ helper/inducer T cells, were observed and were termed "tertiary T-nodules." It is suggested that T-nodules represent the paracortical counterparts of B-lymphoid follicles and are the in vivo equivalents of DC/T-cell clusters observed in vitro. According to their cellular composition and localization in the lymph node, "primary" and "secondary" T-nodules probably represent subsequent maturation stages of distinctive nodular paracortical structures, which play an important role in the presentation of antigens to helper/inducer T cells and in the proliferation of antigen-responsive T cells. Their close topographic relationship to B-lymphoid follicles may indicate their role in the extrafollicular generation of antibody-forming cells.

Antibodies, Monoclonal↗

Spontaneous pituitary gonadotroph nodules in aging male Lobund-Wistar rats.

Spontaneous pituitary changes with aging were studied in 130 male Lobund-Wistar rats by light and electron microscopy and immunohistochemistry. These 69 healthy rats (6, 18, and 30 months) and 61 moribund rats (17-50 months) had been maintained in four different groups with the following environmental conditions: conventional full fed, convention food restricted, germ free-full fed, and germ free-food restricted. Gonadotroph nodules were the most frequent proliferative lesions (27 rats). It was difficult to determine whether these nodules were hyperplastic or neoplastic. They were found in aging rats (26 months or older) and their development was delayed by food restriction and germ-free status parallel to prolongation of life-span. No significant difference in incidence of gonadotroph nodules was demonstrated among the four groups. Six lactotroph adenomas, a thyrotroph nodule, and a mixed thyrotroph and lactotroph nodule were also noted in aging rats (30 months or older). In extranodular adenohypophyses, variable numbers of hyperactive gonadotrophs histologically similar to those in gonadotroph nodules were observed in almost all rats including 6-month rats, suggesting that gonadotrophs were continuously hyperactive during their lifetime from an early stage. The mechanism accounting for the development of gonadotroph nodules remain to be established. It can be concluded that food restriction and germ-free status may have a retarding effect but no preventative role in the development of gonadotroph nodules, which are the most common age-associated pituitary lesions of male Lobund-Wistar rats.

Aging↗

Hepatic foci of cellular and enzymatic alteration and nodules in rats treated with clofibrate or diethylnitrosamine followed by phenobarbital: their rate of onset and their reversibility.

The histologic appearance and cytochemical characteristics of foci of hepatic cellular alteration, hepatic nodules, and hepatocellular carcinomas occurring in male Sprague-Dawley rats treated with the hypolipidemic agent clofibrate (CAS: 637-07-0), with phenobarbital (CAS: 50-06-6), or with diethylnitrosamine [(DENA) CAS: 55-18-5] followed by phenobarbital were studied after treatment periods from 1 month to 2 years. Rats treated with clofibrate revealed foci of cellular alteration that were more often basophilic and occurred slightly sooner (wk 42) than those in untreated controls (wk 60). Of 36 rats that had received 68 or more weeks of continuous clofibrate, 19 had hepatic nodules. Of the 11 nodules examined cytochemically, none was gamma-glutamyltransferase (gamma-GT) positive and 2 were positive to glucose-6-phosphate dehydrogenase (G-6-PD) under oxygen. In rats withdrawn from clofibrate for 16-18 weeks after 68-95 weeks of clofibrate, 0 of 14 had nodules. In several of these rats zones of hepatic scarring were observed, suggesting the reversibility of the nodules. Phenobarbital alone had little effect on the incidence of foci of cellular alteration, although the number of gamma-GT-positive foci was increased. DENA followed by phenobarbital led to the early appearance of foci of cellular alteration (from wk 4), of nodules (from wk 13), and of hepatocellular carcinomas (from wk 26). gamma-GT activity was raised in most of these nodules and carcinomas, while G-6-PD activity was raised in only 3 of 9 nodules but in all 9 carcinomas examined. DENA-phenobarbital given for 13 or 26 weeks followed by withdrawal of phenobarbital for 28 and 26 weeks, respectively, produced an essentially similar pattern of lesions. In view of the growing recognition of the nonspecificity gamma-GT as a marker of carcinogen-initiated foci, the value of G-6-PD (under oxygen) as a marker merits further investigation.

Animals↗

The composite nodule. A structural and functional unit of the reactive human lymph node.

The relationship between T nodules and adjacent B-lymphoid follicles was investigated in 37 reactive lymph nodes by light microscopy and combined enzyme immunohistochemistry. In 16 cases (43%), T nodules and adjacent B-lymphoid follicles were unified in an ovoid, distinct nodular structure termed a "composite nodule." The composite nodule comprises two separate domains. The peripheral, subcapsular B domain contains all stationary and migratory elements of the B-lymphoid follicle, ie, B1+ B-cells, OKT4+, Leu 3a+ helper/inducer T cells, HLA-DR+ dendritic reticulum cells, and ANAE+, AcPhase+ tangible body macrophages and is surrounded by a B1+, HLA-DR+ lymphocytic corona displaying focal adenosine triphosphatase (ATPase) and alkaline phosphatase (AlkPhase) activity. The deep, paracortical T-domain contains all elements of the T nodule, ie, OKT4+, Leu3a+ helper/inducer T cells, high endothelial venules and HLA-DR+, ATPase+ interdigitating reticulum cells. The composite nodule is surrounded by a rim of ATPase+, AlkPhase+ high endothelial venules. Both domains are subject to changes in volume; thus, in follicular hyperplasia, the B domain enlarges at the cost of the T domain, and the reverse may occur in T-zone hyperplasia. Based on the striking resemblance between the composite nodule and the white pulp of the spleen, it is suggested that the composite nodule plays a major role in the triggering, helper-T-cell-dependent stimulation and subsequent maturation of antigen-responsive B cells into antibody-secreting plasma cells.

Adenosine Triphosphatases↗

The incidence of thyroid carcinoma in solitary cold nodules and in multinodular goiters.

The incidence of carcinoma in patients with multinodular goiters has been reported to be considerably lower than in patients with a single cold nodule. However, the definition of a "single cold nodule" is highly subjective and has therefore been modified by qualifiers such as "clinically solitary" or "clinically dominant." In this retrospective study, we find no significant difference in the incidence of carcinoma in patients with multinodular goiters compared with patients with a solitary cold nodule confirmed by operation and histopathologic examination. In a consecutive series of thyroidectomies over a 22-year period, all patients with factors predisposing them to neoplasia, such as a history of radiation exposure and thyroiditis, were eliminated. Furthermore, all patients thought to have additional nodules documented by gross examination at operation or subsequently by histopathologic examination were also eliminated. The remaining 69 patients with clinically evident multinodular goiters were compared with the remaining 96 patients with a solitary cold nodule. The incidence of carcinoma in the 96 patients with a solitary cold nodule was 17%. In the 69 patients with clinically evident multinodular goiters, the incidence of carcinoma was 13%. The difference is not significant. It is of interest that male patients with multinodular goiters had the highest incidence of carcinoma at 29%, whereas, males with a solitary cold nodule had an incidence of only 13%. In conclusion, once known factors that predispose patients to neoplasia are eliminated, there does not seem to be a significant difference in the incidence of thyroid carcinoma between patients with operatively and histopathologically proved solitary cold nodules and those with multinodular goiters.

Carcinoma↗

A sequential quantitative study of the reversibility or irreversibility of liver hyperplastic nodules in rats exposed to hepatocarcinogens.

The behavior of hyperplastic nodules following an in vivo short-term screening test for hepatocarcinogens was studied. Rats were injected ip with 200 mg/kg body weight of diethylnitrosamine (DEN), given basal diet containing 200 ppm of N-2-fluorenylacetamide (2-FAA) (group 1), 1000 ppm of the alpha-isomer of 1,2,3,4,5,6,-hexachlorocyclohexane (alpha-BHC) (group 2) or basal diet (group 3) from week 3 to week 8, and then given basal diet and tap water. They were subjected to partial hepatectomy at the end of week 3. Animals were killed at weeks 4, 6, 8, 10, 20, 30, 40, and 50. A significant disappearance of hyperplastic nodules following the cessation of carcinogen treatment was observed in group 1, but was not evident in groups 2 and 3. With gamma-glutamyltranspeptidase (GGTase) as a positive marker and adenosine triphosphatase (ATPase) as a negative marker, hyperplastic nodules were classified into 3 different phenotypic categories, i.e., (1) GGTase-positive and ATPase-negative, (2) GGTase-positive, and (3) ATPase-negative. The percentages of GGTase-positive and ATPase-negative hyperplastic nodules were almost 80 approximately 90% in group 1 and 70 approximately 80% in groups 2 and 3. Some of the hyperplastic nodules were necrotic from week 8 in groups 1 and 2, and from week 20 in group 3. Subsequently, the numbers of necrotic hyperplastic nodules increased with time. Hepatocellular carcinomas were found at weeks 30, 40, and 50 in group 1, and at weeks 40 and 50 in group 2. Significantly higher incidences of cancer were found in group 1 than in group 2. The hepatocellular carcinomas were also classified enzyme-histochemically into 3 different phenotypic categories as for hyperplastic nodules, but the percentage (20%) of GGTase-positive and ATPase-negative hepatocellular carcinomas was significantly lower than that (70 approximately 90%) of GGTase-positive and ATPase-negative hyperplastic nodules in each group.

Adenosine Triphosphatases↗

Primary synovial chondrometaplasia. Histologic variations in the structure of metaplastic nodules.

Eight cases of primary synovial chondrometaplasia have been evaluated with respect to 1) number of metaplastic nodules, 2) their location in relation to the surface of the synovium, 3) the histochemical composition of the matrix of the nodules; number of nodules with 4) cystic degeneration, 5) osteoclastic/chondroclastic activity at the margin, 6) invasion of connective tissue and 7) calcification and/or ossification. Furthermore, the pleomorphism and hyperchromatism of the chondroid cells and their nuclei and number of mitoses were evaluated. The number of metaplastic nodules varied greatly, from a few to more than a hundred. Most nodules were located at the level of the original synovial surface or in the pedunculated prominences. Histochemically, two types of nodules were found and in about equal numbers. Connective tissue invasion, calcification and ossification were the most frequent changes; whereas cystic degeneration, which has not been described before, was the rarest. Only one of the cases showed all the different changes, and these within a considerable number of the nodules. Variation of the chondroid cells and their nuclei was considered as an expression of degenerative changes, and mitoses were not found. Two of the cases had a tumor-like accumulation of metaplastic nodules.

Adolescent↗

[Histological studies of multiple subperitoneal nodules produced by prolonged administration of estrogen (author's transl)].

It has been reported that multiple peritoneal fibroids were produced in guinea pigs treated with large doses of estrogens, and the nodules regressed when the steroid stimulant was discontinued. Recently, these experimental nodules were considered to be simulating the disseminated pattern of Leiomyomatosis Peritonealis Disseminata (LPD). Although these experimental nodules were considered to be composed of fibroblasts by light-microscopic studies, LPD was verified to be composed of smooth muscle by electronmicroscopic studies. Therefore, it is indispensable to study these experimental nodules by electronmicroscopy, when we discuss about the similarities between experimental nodules and LPD. Guinea pigs were treated with various doses of estradiol benzoate (E) [40, 80, 100, 200 microgram/day, thrice a week, intramuscular injection]. After treatment for three months, every dose of E produced the lesions simulating the disseminated pattern of LPD: multiple nodules in various sizes, scattered on the surface of the uterine horn, peritoneum, spleen and pancreas, and in the omentum and mesocolon. Ultrastructurally, the nodules were composed of the cells resembling fibroblast. We conjectured that estrogen differentiates and proliferates the cells of the features of fibroblast-like cells from subcoelomic mesenchyme, resulting in the production of multiple superitoneal nodules simulating the disseminated pattern of LPD.

Animals↗