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Stromal nodules in benign prostatic hyperplasia.

OBJECTIVE: Stromal nodules from benign prostatic hyperplasia (BPH; n = 375 from autopsy, n = 100 from biopsy specimens) were investigated with regard to cytoskeletal components, topography, vascularization, leukocytic infiltrates, and proliferative activity. METHODS: The nature of stromal nodules was studied by histopathology and immunohistochemistry, using antibodies against alpha-actin, desmin, myosin, vimentin, BMA-120, factor VIII, CD3, CD4, CD20, CD34, CD45RO, CD68, PCNA, and MiB1. RESULTS: The findings lead to an extended classification of stromal nodules in BPH: immature mesenchymal (IM; 8.8%), fibroblastic (FB; 65.2), fibromuscular (FM; 21.6), and smooth muscular (SM; 4.4%). The different types occurred in all age decades in a similar distribution (FB > FM > IM > SM). Topographical studies (modified zonal subdivision of McNeal) revealed stromal nodules predominantly in the transitional zone (n = 286), less in the central zone (n = 78), occasionally in the peripheral zone (n = 11), and predominantly in the periurethral (n = 287) and less in the intermediate (n = 84) and subcapsular (n = 4) regions. The different types of nodules presented a distinct vascular pattern. FB, FM, and SM nodules showed significantly increased diffuse infiltrates of T lymphocytes-mainly T helper cells (mean 73%)-and an increase of B lymphocytes. Proliferative activity in the nodules was not observed. Stromal nodules were not observed in normal nonhyperplastic prostates; they only occurred in combination with hyperplastic nodular glandular proliferates. CONCLUSIONS: The findings are suggestive of a maturational sequence of stromal nodules in BPH and of a possible significance of immunocompetent cells in the development of stromal nodules and further suggest that both stroma and epithelium of the prostate respond with nodular hyperplasia to the stimulus, which causes BPH.

Adult↗

[Acquired regressive cutaneous non-Langerhans-cell histiocytosis in an infant].

INTRODUCTION: Cutaneous histiocytosis of childhood often regresses spontaneously without treatment. In some cases however, it is difficult to differentiate aggressive forms and electron microscopy and immunohistochemistry can be a valuable help. We report a case of cutaneous histiocytosis in a child which illustrates the difficulties encountered in the classification of histiocytosis. CASE REPORT: An 18-month old girl was brought to consultation with a cutaneous nodule which had developed at the age of 15 months on the labia majora. A second nodule on the chin had regressed spontaneously. Histology showed evidence of dermal histiocyte proliferation. Immunohistochemistry demonstrated is non Langerhans nature which was confirmed by electron microscopy. The clinical course was benign after surgical exeresis of the lesion on the labia majora. DISCUSSION: Different forms of histiocytosis can be classed on the basis of 4 criteria: Langerhans origin or not, acquired or congenital forms, cutaneous or visceral involvement, benign or malignant course. Four diagnosis were possible in our case: histiocytosis X, self-healing congenital histiocytosis, benign cephalic histiocytosis, juvenile xanthogranuloma. We preferred to use the descriptive term of acquired regressive cutaneous non-X histiocytosis of childhood.

Female↗

Role of rhizobial lipo-chitin oligosaccharide signal molecules in root nodule organogenesis.

The role of oligosaccharide molecules in plant development is discussed. In particular the role of the rhizobial lipo-chitin oligosaccharide (LCO) signal molecules in the development of the root nodule indicates that oligosaccharides play an important role in organogenesis in plants. Recent results of the analyses of structures and of the biosynthesis of the LCO molecules are summarized in this paper. The knowledge and technologies that resulted from these studies will be important tools for further studying the function of LCO signals in the plant and in the search for analogous signal molecules produced by plants.

Carbohydrate Sequence↗

The early nodulin transcript ENOD2 is located in the nodule parenchyma (inner cortex) of pea and soybean root nodules.

A pea cDNA clone homologous to the soybean early nodulin clone pGmENOD2 that most probably encodes a cell wall protein was isolated. The derived amino acid sequence of the pea ENOD2 protein shows that it contains the same repeating pentapeptides, ProProHisGluLys and ProProGluTyrGln, as the soybean ENOD2 protein. By in situ hybridization the expression of the ENOD2 gene was shown to occur only in the inner cortex of the indeterminate pea nodule. The transcription of the pea ENOD2 gene starts when the inner cortical cells develop from the nodule meristem. In the determinate soybean nodule the ENOD2 gene is expressed in the inner cortex as well as in cells surrounding the vascular bundle that connects the nodule with the root central cylinder. The term 'nodule inner cortex' is misleading, as there is no direct homology with the root inner cortex. Therefore, we propose to consider this tissue as nodule parenchyma. A possible role of ENOD2 in a major function of the nodule parenchyma, namely creating an oxygen barrier for the central tissue with the Rhizobium containing cells, is discussed.

Amino Acid Sequence↗

Pulmonary small lymphocytic lymphoma (mucosa-associated lymphoid tissue type) associated with pulmonary hyalinizing granuloma.

A case of pulmonary hyalinizing granuloma (PHG) and concomitant low-grade, small lymphocytic lymphoma of the lung is presented. This is the first occurrence of pulmonary lymphoma in patients with PHG ever reported. The infiltrates around a left lower lobe nodule with left pleural effusion and thickening seen on chest CT were histologically proven to be lymphomatous infiltrates of the lung, pleura, and chest wall muscle. We believe that the lymphoma developed around the nodule and spread to the pleura and muscle in our patient. When infiltrates around the nodules, pleural effusion, or adenopathy are developed in a patient with proven PHG, close follow-up, biopsy, or careful cytology should be seriously considered to rule out a developing lymphoma.

Granuloma↗

Hepatocarcinogenesis in rodents and humans.

In hepatocarcinogenesis in rodents, induction of foci and nodules comprising clonally proliferated initiated cells is considered to be essential for the future development of carcinomas. Nodules in human cirrhotic liver, though known to be associated with a high hepatocellular carcinoma risk, have generally been regarded as regenerative in nature, and not the result of clonal or neoplastic cell proliferation, on a morphological basis. However, when we analyzed 83 cirrhotic nodules from 11 HBV carrier patients, utilizing hepatitis B virus (HBV) integration as a marker for clonal proliferation, we found the existence of clonal populations of more than 10(5) hepatocytes in 26 (31.3%) of them. Although such clonal cell populations are morphologically not discernible from neighboring hepatocytes, they may have particular histogenetic significance in human hepatocarcinogenesis and clearly deserve further investigation. Allelotype analysis of mouse hepatocellular carcinomas (HCC), induced by a single dose of diethyl nitrosaminine in C3H/MSM F1 hybrids, revealed no remarkable alterations in the original tumors when microsatellite probes were used, but loss of heterozygosity of chromosome 4 at extremely high frequency (95%) in cultured cell lines derived from these HCC. The shortest common region was about 10 cM distal to the interferon alpha gene, in which the p16 gene is located. The results indicated that loss of gene function, most probably including that of the p16 gene, may be essential for immortalization of cultured hepatocytes but that it may not play any role in initiation or early events in mouse hepatocarcinogenesis in vivo. The mouse HCC used for analysis in this study may be comparable with human HCC at an early stage, for which only very limited genetic alterations have so far been identified.

Alleles↗

Radiation enhancement of lung nodule formation in mice is not potentiated by treatment with a perfluorochemical emulsion and carbogen.

The ability of intravenously-injected mouse mammary tumor cells to form lung tumors is increased by irradiation of the thorax 24 h previously. We examined the effects of treatment with a perfluorochemical emulsion (Fluosol-DA, 20%) plus carbogen before and during irradiation on the radiation-induced enhancement of lung nodule formation. We found no evidence that treatment with Fluosol plus carbogen altered the development of tumor nodules in irradiated mouse lungs.

Animals↗

Effect of light, dark, and temperature on root nodule activity (acetylene reduction) of soybeans.

The objectives of this study were (a): to define the effects of light, dark, and temperature on nodule activity (acetylene reduction), and (b) to establish the contributions of reserve carbohydrate and recent photosynthate to the support of nodule function. An in situ assay of nodule activity was developed for use with intact, hydroponically grown soybeans (Glycine max [L.] Merr. cv. Calland).Nodule activity of 35-day-old plants grown in controlled environment chambers decreased during a 10-hour dark period at 18 C, compared with activity during the preceding and subsequent 14-hour light periods at 27 C. In contrast, plants that were maintained at a constant 27 C did not vary in nodule activity during diurnally varying dark and light exposure. Nodules of plants exposed to diurnal 18 and 27 in 24-hour continuous dark were less active at 18 C than at 27 C. At constant 27 C, nodule activity was sustained throughout the 24-hour dark period. Thus, nodule activity was independent of short term dark periods but dependent on temperature; nodule activity was decreased at the lower temperature.Temperature also affected the nodule activity of plants maintained in the light. Exposure of shoots and roots of intact plants to the lower temperature (5 hours at 18 C) during the light period resulted in a marked decrease in nodule activity, compared with that of plants maintained at 27 C. Exposure of only the shoot portion to 18 C (roots were maintained at 27 C) resulted in a similar decrease in nodule activity.Nodules of plants exposed to 10 days of diurnally variable dark, light, and temperature had high activity in the light at 27 C and low activity in the dark at 18 C. Nodule activity of plants at a constant 27 C was not affected by diurnally variable dark and light exposure throughout the 10-day period, although activity generally increased with time due to increased nodule mass. At a constant 27 C, nodules of intact plants in continuous dark sustained activity through 72 hours before declining to zero by 7 days. At diurnally varying 18 and 27 C in continuous dark, peak diurnal nodule activity was sustained through 5 days, and then declined to zero by 8 days. Analyses of the carbohydrate content of tissue harvested from this study suggested use of reserve photosynthate (primarily of shoot origin) in support of nodule activity in the absence of concurrent photosynthesis.

Journal Article↗

A new proline-rich early nodulin from Medicago truncatula is highly expressed in nodule meristematic cells.

We cloned and characterized MtPRP4, a new member of the repetitive proline-rich protein gene family in Medicago truncatula. The sequence of MtPRP4 predicts a 62-kD protein consisting of a 22-amino acid N-terminal signal peptide and a 527-amino acid repetitive proline-rich domain composed of three repetitive pentapeptide motifs arranged into two decapeptide repeats: PPVEKPPVHK and PPVEKPPVYK. MtPRP4 is the largest PRP described to date and contains repeated motifs that have not previously been found together in a single polypeptide. RNA gel blot experiments detected MtPRP4 transcripts in symbiotic root nodules, but not in roots, hypocotyls, or leaves. Accumulation of MtPRP4 transcript was an early response to Rhizobium inoculation and did not depend on nodule infection. In situ hybridization experiments demonstrated that MtPRP4 was expressed early in the development of the nodule meristem and that expression was highest in the meristematic cells of mature indeterminate nodules. These data support the proposition that an important early response of legume host roots to Rhizobium involves remodeling the host extracellular matrix and that proline-rich wall proteins play an important role in this architectural modification.

Amino Acid Sequence↗

Lipopolysaccharide profiles from nodules as markers of bradyrhizobium strains nodulating wild legumes.

To develop the use of electrophoretic lipopolysaccharide profiles for Bradyrhizobium strain identification, we studied the feasibility of using electrophoresis of whole legume nodule homogenates to obtain distinctive lipopolysaccharide profiles. The electrophoretic patterns were the same whether we used nodule extracts, bacteroids, or cultured bacteria as samples, and there was no evidence of changes in the ladder-like pattern during the nodulation process. To assess the reliability of using lipopolysaccharide profiling performed with individual nodules for studying the diversity and microdistribution of the rhizobia nodulating wild shrub legumes, we used a population of Adenocarpus foliolosus seedlings. We obtained 75 different profiles from the 147 nodules studied. There was no dominant profile in the sample, and a plant with different nodules generally produced different profiles. Electrophoresis of legume root nodules proved to be a fast and discriminating technique for determining the diversity of a bradyrhizobial population, although it did not allow the genetic relationships among the nodulating strains to be studied.

Journal Article↗

Models for the study of cementogenesis.

Cementum is a mineralized tissue that acts to connect the periodontal ligament to the tooth root surface. Its composition is very much like bone, being comprised mainly of type I collagen, inorganic mineral and noncollagenous proteins, however the origin of the cells and factors necessary for cementum formation have yet to be elucidated. Our laboratory has focused on the role that adhesion molecules, and their cell surface receptors, play in the formation of cementum and tooth root. In order to study this, we used a mouse molar as a model system. This system enabled us to study the formation of four distinct mineralized tissues; bone, cementum, dentin and enamel at various stages of their development. For these studies, we initiated experiments to examine potential cementoblast progenitor cells, in vitro. As a first step, we show that dental papilla and dental follicle cells, n vitro, obtained from molar tissues at day 21 of development, induce mineralized nodules, in vitro. In addition, we obtained tissues from mice where defects in root development may exist and determined bone sialoprotein (BSP) protein expression, a mineralized tissue specific adhesion molecule, in such tissues. As discussed here, we found that osteopetrotic (op/op) mice have delayed and/or defective root development and BSP does not localize in the dental tissues, at day 33 of development. In addition, dentin formation was defective and odontoblasts appeared immature, based on morphological examination. In contrast, the day 33 control molars demonstrated positive staining for BSP localized to root cementum, with normal formation of dentin.

Amelogenesis↗

Phenylacetate is an inhibitor of prostatic growth and development in organ culture.

PURPOSE: Benign prostatic hyperplasia (BPH) is the most common proliferative disease affecting men, and the obstructive uropathy it causes results in serious morbidity and financial cost. Phenylacetate (PA) is a small molecule that is a product of phenylalanine metabolism and is normally present in the mammalian circulation at very low levels. It has long been safely used in humans to treat the hyperammonemia resulting from urea synthesis disorders and liver failure. It has recently been investigated as an anticancer agent because it decreased growth and increased differentiation of a variety of human neoplasms, including prostate cancer in which a phase I trial has recently been completed. MATERIALS AND METHODS: Because of PA's growth-inhibitory effects on a variety of cell lines and the idea that BPH is due to a reawakening of embryonic-like inductive activity in prostatic stromal cells, which then induce development of epithelial nodules, we examined the effect of PA on serum-free organ cultures of developing rat prostates. RESULTS: We found that PA markedly decreased rat prostatic growth and ductal morphogenesis at concentrations that have previously been well tolerated in patients. In ventral prostates grown for 7 days in organ culture, histodifferentiation was inhibited as measured by a marked decrease in ductal lumen formation and ductal branching morphogenesis. This inhibition of differentiation was confirmed by using cytokeratin antibodies specific for basal and luminal cells. Synthesis of DNA was also significantly decreased per organ with PA. The growth inhibitory effects of PA were reversible, and the mechanism did not appear to be due to glutamine or glycine deprivation, or androgen receptor inhibition. CONCLUSIONS: In common with earlier studies, we found that PA inhibits prostatic growth; however, in our organ culture system, differentiation was also largely inhibited. These studies indicate that there may be a role for PA in treating BPH or in elucidating the mechanism by which it occurs since BPH apparently involves the neoformation of ductal-acinar tissue in aged men via mechanisms fundamentally similar if not identical to those in fetal prostatic development.

Animals↗

Gene expression analysis reveals evidence for inactivation of the TGF-beta signaling cascade in autonomously functioning thyroid nodules.

Molecular events that lead to the development of autonomously functioning thyroid nodules (AFTNs) are somatic mutations of the thyrotropin receptor (TSHR) in approximately 60% of the nodules and less frequently, somatic mutations in the Gsalpha protein. However, AFTNs without known mutations indicate that other causes remain to be identified. Moreover, the impact of constitutively activating TSHR mutations on the signal transduction network of the thyroid epithelial cell is unknown. We therefore investigated gene expression in 15 AFTNs and their surrounding tissue using Affymetrix GeneChips. Most prominently, data analysis revealed a changed pattern of gene expression in the TGF-beta signaling cascade and 25 differentially regulated genes in AFTNs, including thyroid peroxidase, type I iodothyronine deiodinase and sialyltransferase (SIAT) 1. Strikingly coexpression of SIAT 1 and TSHR in COS-7 cells increased TSH binding and cell surface expression of the TSHR. Moreover, differences in gene expression patterns for AFTNs with and without TSHR mutations indicate specific alterations of signal transduction in AFTNs without TSHR mutations. These results suggest that AFTNs with TSHR mutations harbor further mechanisms of forward stimulation. Furthermore, they give important leads to elucidate the molecular etiology of AFTNs without TSHR mutations.

Animals↗

The effect of age on the histopathogenesis of 7,12-dimethylbenz(a)-anthracene-induced mammary tumors in the Lewis rat.

The influence of age at time of DMBA administration on (1) the histopathogenesis and site of mammary tumor origin and (2) the precancerous nature of DMBA-induced mammary dysplasias was examined in Lewis rats between 25 and 200 days of age. Rats were killed at various times after carcinogen treatment and the numbers of tumors and dysplasias were recorded from microscopic examination of mammary gland wholemounts. We found that, in all age-groups tested, mammary tumors always appeared to originate within mammary end-buds and terminal ductules and that terminal ductule hyperplasia appeared to be an early stage in tumor formation. Age-related differences in susceptibility to tumor development were paralleled by similar differences in susceptibility to the development of terminal ductule hyperplasias. In contrast, although age-related differences in susceptibility to the development of hyperplastic alveolar nodules were also noted, they did not correspond to those observed for tumor development. Thus, hyperplastic alveolar nodules did not appear to be a site of tumor origin in situ or directly related to tumor development.

9,10-Dimethyl-1,2-benzanthracene↗

In situ expression of the GmNMH7 gene is photoperiod-dependent in a unique soybean (Glycine max [L.] Merr.) flowering reversion system.

Soybean is a short-day plant and its flowering process can be reversed when switching from short-day to long-day conditions. Flowering reversion provides a useful system to study the flowering process in both forward and backward directions. In this study, we optimized a soybean flowering reversion system using a photoperiod-sensitive cultivar Zigongdongdou. Three types of terminal structures were found during flowering reversion: reversed terminal raceme (RTR), short terminal raceme (STR), and vegetative terminal (VT). The relative frequency of these terminal structures during flowering reversion under long day was dependent on the duration of the prior short day (SD) pretreatment. This process is phytochrome dependent and young plants were more susceptible to flowering reversion. Leaf removal increased the minimal SD period needed for the induction of STR. To demonstrate the application of this system, we studied the patterns of in situ expression of the GmNMH7 gene during flowering development and reversion. NMH7 family members encode MADS-box proteins and are unique in legume families since their expression can be detected in both developing flowers and nodules. In situ hybridization experiments using plants grown under different photoperiod cycles provided several lines of evidence supporting a close relationship between GmNMH7 gene expression and floral development in soybean. Furthermore, it seems that GmNMH7 may participate in flower development at different stages. Interestingly, the expression pattern of GmNMH7 in root nodules was also found to be regulated by photoperiod. These results support the notion that the photoperiod sensitive GmNMH7 gene may play multiple roles in growth and development in soybean.

Amino Acid Sequence↗

Reducing effects of rodent malaria on hepatic carcinogenesis induced by dietary aflatoxin B1.

The present study was undertaken to evaluate the effects of Plasmodium berghei infection on the development of liver tumors induced in male Buffalo rats by aflatoxin B1 (AFB1). Intraperitoneal (i.p.) injection of 10(6) parasitized red blood cells (pRBC) into the rat 12 days prior to administration of 2 ppm dietary AFB1 for 10 weeks diminished hepatocellular carcinoma (HCC) induction compared to that observed in rats given AFB1 alone at weeks 60-82. No animals in a control group developed HCC lesions, while only 1 of 22 rats treated with P. berghei alone developed a neoplastic nodule at week 82. These data suggest a reducing effect of P. berghei on the development of liver tumors induced by AFB1 in male Buffalo rats.

Aflatoxin B1↗

Assay of substances stimulatory to legume nodule formation.

Two methods were developed for the assay of substances stimulatory to the nodulation of bean (Phaseolus vulgaris) roots growing from segments of hypocotyl tissue. Coconut water was the chief source of active material, but extracts of cotyledons, hypocotyls and leaves of beans and of horse chestnut fruits were also stimulatory. High concentrations of nitrate improved nodulation both in the presence and absence of coconut water. The ash of coconut water was inactive. Whole alfalfa seedlings formed nodules in the dark when grown in the split medium, but nodulation was not improved by the addition of coconut water.

Journal Article↗

Suppression of spontaneous development of uterine adenomyosis and mammary hyperplastic alveolar nodules by Chinese herbal medicines in mice.

The effects of traditional Chinese herbal remedies, Shakuyaku-kanzo-to (SKT) and Hachimijiou-gan (HJG), on the spontaneous development of uterine adenomyosis and mammary hyperplastic alveolar nodules (HAN) were examined in an experimental animal model using SHN strain of mice. Female mice were provided with the chow containing 1% of SKT or HJG during 25-150 days of age. At 150 days of age, SKT treatment showed significantly lower incidence of adenomyosis, and HJG treatment resulted in a significantly lower incidence of HAN when compared to a control chow containing no medicines. Long-term exposure to these herbal medicines affected little serum prolactin (PRL) level, estrous cycle, food intake and body growth. Thus, the present mouse data suggest that the oral administration of these herbal medicines is a useful tool for the treatment of uterine adenomyosis or mammary disorder such as cystic mastitis.

Adenomyoma↗