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PubMed2005

[Changes in thyroid volume after radioactive iodine therapy in patients with single toxic thyroid nodule].

Radioactive iodine (131I) is a well-established therapeutic modality in the treatment of toxic solitary autonomous thyroid nodules. This method is preferred in patients with small, benign nodules. The aim of our study was to investigate the effects of radioiodine therapy on thyroid size in patients with a solitary toxic thyroid nodule. 22 patients with single nodule in USG and confirmed "hot" nodule in scintigraphy were enrolled in the study. Thyroid and nodule volume were determined by ultrasound before, 3 and 6 months after the administration of 131I. Thyroid function was assessed by TSH level prior to the treatment and 6 weeks after the therapy. Thyroid volume and nodule size decreased significantly within 3 and 6 months after 131I treatment. The mean reduction of thyroid volume within 6 month after treatment was 32%. Reduction in thyroid volume and nodule, size was significantly greater within first 3 months than within next 3 months. Patients with smaller nodules (less than 70% of thyroid volume) were characterized by greater reduction of goiter size than patients with nodules bigger or equal to 70% of thyroid volume.

Dose-Response Relationship, Radiation↗

PubMed2006

Tissue characterization of solitary pulmonary nodule: comparative study between helical dynamic CT and integrated PET/CT.

UNLABELLED: Recent advances in the technology of helical multidetector CT allow precise evaluations of nodule hemodynamics. In addition, the efficacy of tissue characterization has improved, and now sensitivity and specificity of >90% are achieved. Moreover, the efficacy of PET for the tissue characterization of solitary pulmonary nodules (SPNs) has also become of importance. The purpose of this study was to compare the diagnostic accuracy of helical dynamic (HD) CT (HDCT) and integrated PET/CT for pulmonary nodule characterization. METHODS: One hundred nineteen patients with an SPN underwent both HDCT (unenhanced scans, followed by series of images at 30, 60, 90, 120 s and at 5 and 15 min after intravenous injection of contrast medium) and integrated PET/CT. On HDCT, a nodule was regarded as malignant with a net enhancement of > or =25 Hounsfield units (HU) and a washout of 5-31 HU. On integrated PET/CT, nodules were considered malignant with a > or =3.5 maximum standardized uptake value and an 18F-FDG uptake greater than that of mediastinal structures. The sensitivity, specificity, and accuracy of the 2 modalities for malignancy were compared using the McNemar test. RESULTS: There were 79 malignant and 40 benign nodules. The sensitivity, specificity, and accuracy for malignancy on HDCT were 81% (64/79 nodules), 93% (37/40), and 85% (101/119), respectively, whereas those on integrated PET/CT were 96% (76/79), 88% (35/40), and 93% (111/119), respectively (P = 0.008, 0.727, and 0.011, respectively). All malignant nodules were interpreted correctly on either HDCT or PET/CT. CONCLUSION: Integrated PET/CT is more sensitive and accurate than HDCT for the malignant nodule characterization; therefore, PET/CT may be performed as the first-line evaluation tool for SPN characterization. Because HDCT has high specificity and acceptable sensitivity and accuracy, it may be a reasonable alternative for nodule characterization when PET/CT is unavailable.

Adult↗

PubMed1994

[Echography of thyroid nodules. The echography specialist facing the clinician's requirements].

The risk of malignancy in cases of unique non-functional thyroid nodules ranges from 5 to 20% and since definitive diagnosis can only be provided by the pathology examination, surgical removal could be planned in all cases. The clinician however also has the objective of proposing surgery to as few patients with benign nodules as possible and thus calls upon the echographist to help distinguish between malignant and benign nodules. Thus orders for echography carry an intrinsic request for diagnostic arguments, a precise analysis of the characteristics of the nodule and a description of possible multinodular dystrophy as well as an estimation of the probability of malignancy. The echographist's report must include a precise description of each thyroid lobe, the localization of the nodule, its size, contour, echostructure, echogenicity and calcifications. The cervical lymph node chains must also be explored. An analysis of the surrounding parenchyma can frequently confirm multinodular dystrophy. The size of the nodule is the determining factor in predicting malignancy. While for very small nodules, less than 1 cm in diameter, the malignant nature cannot be reasonably predicted, and inversely for very large nodules, invading an entire lobe, it is usually evident, for intermediate sized nodules, echography is a strategic diagnostic tool. No sign is pathognomonic but an association of arguments can favour malignancy: an unique isolated nodule, irregular contours, lymph node enlargement greater than 1 cm. Hypoechogenicity is another important characteristic with a positive predictive value of 50% to 63%. Overall, the sensitivity of echography is good at 75% with specificity of 61 to 83%.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

PubMed1997

[Contrast-enhanced study of solitary pulmonary nodules with thin-section computed tomography].

INTRODUCTION: Since many benign and malignant pathologic conditions can appear as solitary pulmonary nodules, to establish nodule nature is always necessary for correct patient management. Recently, some authors have demonstrated the effectiveness of incremental dynamic CT in distinguishing cancerous from noncancerous lesions. The purpose of this work is to report our personal experience in this field. MATERIAL AND METHODS: We reviewed the incremental dynamic CT scans of 21 patients with a solitary pulmonary nodule < 3.5 cm phi without any calcifications, cavities and fat--namely, 15 carcinomas, 3 granulomas, 2 hamartomas, 1 abscess. Lesion density was evaluated before and 30 s, 1, 2, 3 and 5 min after contrast agent administration; we used a circular region of interest consisting of the central portion of the nodule in all cases and of 60-70% of its area in most cases. We subdivided the nodules into two groups, according to their enhancement: the nodules with > 20 HU and those with < 20 HU. All the lesions were submitted to surgery and histologic studies. RESULTS: Fourteen of 15 carcinomas and one hamartoma had contrast enhancement > 20 HU; an abscess exhibited marked ring-shaped contrast enhancement (positive predictive value: 87%). One carcinoma, three granulomas and one hamartoma had no contrast enhancement, or else it was < 20 HU (negative predictive value: 80%). DISCUSSION: Recently, some authors have demonstrated that malignant nodules, studied with incremental dynamic CT, have higher contrast enhancement than benign nodules. A value > 20 HU is a good predictor of malignancy (positive predictive value: 90%) and, conversely, a value < 20 HU is an unquestionable sign of benignity (negative predictive value: 100%). Our findings confirm the positive predictive value of enhancement > 20 HU, but not its negative predictive value because we found a malignant nodule without contrast enhancement. CONCLUSIONS: Incremental dynamic CT is an effective indicator of solitary pulmonary nodule nature, but its predictive value is not absolute and therefore this technique should be integrated with biopsy in the cases which are clinically or radiologically suspicious.

Contrast Media↗

PubMed1998

[Benign pulmonary nodule: morphological features and contrast enhancement evaluated with contiguous thin-section CT].

The morphological changes in 54 benign lung nodules, including 8 histologically proven nodules of tuberculoma, 10 of focal organizing pneumonia (FOP), 1 of lung abscess and 35 other benign nodules, were evaluated with contiguous thin-section (3mm) CT. In addition, incremental dynamic studies were carried out in 25 of these nodules. The three-dimensional shapes of the nodules were found to be quite varied and were classified into four types: (A) round mass (n = 18), (B) polygonal mass with concave or straight margins (n = 20), (C) oval or band-like mass extending along the bronchovascular bundle (n = 7), (D) oval mass attached to the pleura with broad contact (n = 9). Forty-two (78%) of the 54 nodules were located along the bronchovascular bundle. The maximum increments in CT values over 20HU were observed after contrast enhancement in 18 (72%) of the 25 benign nodules, among which all tuberculomas showed little or no contrast enhancement. The number of small vessels quantified microscopically in teh center of the nodules were minimal in tuberculomas with little enhancement and plentiful in lesions of FOP and abscess which showed marked enhancement. Our results suggest that the differentiation between benign and malignant pulmonary nodules is not possible simply on the basis of the degree of contrast enhancement. Therefore, morphological features and the anatomical relation to the bronchovascular bundles should also be taken into consideration in the diagnosis of pulmonary nodules.

Adult↗

PubMed1990

Cystic thyroid nodules. The dilemma of malignant lesions.

A retrospective study of 221 surgically resected thyroid nodules disclosed that 71 (32%) were cystic and 150 (68%) were solid lesions. Ultrasonography correctly characterized cystic nodules in all but one case. Comparing cystic and solid nodules, there were no differences in patient demographics (mean ages, 47.7 +/- 1.8 SEM vs 45.9 +/- 1.2 years; sex, 78% females both groups), the proportion that were solitary (39% vs 40%), or the nodule size (49% vs 47% greater than or equal to 2 cm in diameter). Of cystic thyroid lesions, 4% were simple cysts, 82% were degenerating benign adenomas or colloid nodules, and 14% were malignant compared with 23% of solid lesions that were malignant. Most cystic lesions (81%) contained bloody fluid. One benign true cyst was filled with thick brown fluid, while clear yellow fluid was repeatedly aspirated from one malignant cystic nodule. Malignant fine-needle aspiration cytology was the best predictor of cancer (100%). Much less predictable were signs of local compression or invasion (43%), a history of head or neck irradiation (33%), cyst recurrence after aspiration (29%), or an increase in the cystic nodule's size (7%). Indeterminate cytology identified malignancy with about half the frequency in cystic lesions as compared with solid nodules (13% vs 27%). The only false-negative fine-needle aspiration cytology occurred in a cystic lesion. In patients with cystic papillary cancers, needle aspirates contained insufficient material for diagnosis in 20% that occurred in no patient with solid papillary carcinoma. The sensitivities and specificities of fine-needle aspiration cytology for solid nodules were 100% and 55%, and for cystic nodules were 88% and 52%. Thus, cystic lesions are as likely as solid thyroid lesions to harbor a malignancy that cannot be predicted from the cyst's clinical characteristics or the patient's demographic data. Although fine-needle biopsy is the best predictor of malignancy in either cystic or solid thyroid lesions, it is slightly less reliable when a thyroid lesion is fluid filled rather than solid. We believe that most cysts not abolished by aspiration should be surgically excised.

Adult↗

PubMedDate not supplied

Sonographic appearances of small hepatic nodules without tumor stain on contrast-enhanced computed tomography and angiography.

PURPOSE: We report the sonographic appearances and pathologic findings for hepatic nodules 2 cm or smaller that were detected by sonography but that did not produce a tumor stain on constrast-enhanced helical CT or digital subtraction angiography. METHODS: Sixty-six nodules 2 cm or less were found by sonography in 39 patients. Sonographically guided needle biopsies were done on all lesions. RESULTS: Twenty-seven nodules were benign nodules, 9 were borderline lesions, and 30 were hepatocellular carcinomas. Benign nodules were significantly smaller than hepatocellular carcinomas (mean size, 1.0 cm versus 1.4 cm, respectively; p <0.00001). Nodules 1 cm or smaller were more likely to be diagnosed as benign nodules (68%) than as either of the other types (32%; p = 0.01). A significantly greater percentage of hepatocellular carcinomas showed a heterogeneous pattern (64%) on sonography compared with benign nodules (25%) and borderline lesions (11%; p = 0.04). In nodules 1 cm or smaller, a homogeneous pattern (68%) was more common than a heterogeneous pattern (32%; p = 0.01). CONCLUSIONS: The nature of small hepatic nodules cannot be determined with sonography. Thus, biopsy remains the only technique for obtaining a definitive diagnosis.

Aged↗

PubMed1989

Effects of transforming growth factor beta and epidermal growth factor on cell proliferation and the formation of bone nodules in isolated fetal rat calvaria cells.

When cells enzymatically isolated from fetal rat calvaria (RC cells) are cultured in vitro in the presence of ascorbic acid and Na beta-glycerophosphate, discrete three-dimensional nodules form with the histologic, immunohistochemical, and ultrastructural characteristics of bone (Bellows et al; Calcified Tissue International 38:143-154, 1986; Bhargava et al., Bone, 9:155-163, 1988). Quantitation of the number of bone nodules that forms provides a colony assay for osteoprogenitor cells present in the RC population (Bellows and Aubin, Develop. Biol., 133:8-13, 1989). Continuous culture with either epidermal growth factor (EGF) or transforming growth factor beta (TGF-beta) results in dose-dependent inhibition of bone nodule formation; however, the former causes increased proliferation and saturation density, while the latter reduces both parameters. Addition of EGF (48 h pulse, 2-200 ng/ml) to RC cells at day 1 after plating results in increased proliferation and population saturation density and an increased number of bone nodules formed. Similar pulses at confluence and in postconfluent multilayered cultures when nodules first begin forming (approx. day 11) inhibited bone nodule formation and resulted in a smaller stimulation of cell proliferation. Forty-eight hour pulses of TGF-beta (0.01-1 ng/ml) reduced bone nodule formation and proliferation at all times examined, with pulses on day 1 causing maximum inhibition. The effects of pulses with TGF-beta and EGF on inhibition of nodule formation are independent of the presence of serum in the culture medium during the pulse. The data suggest that whereas EGF can either stimulate or inhibit the formation of bone nodules depending upon the time and duration of exposure, TGF-B inhibits bone nodule formation under all conditions tested. Moreover, these effects on osteoprogenitor cell differentiation do not always correlate with the effects of the growth factors on RC cell proliferation.

Animals↗

PubMed1990

Decreased expression of the growth hormone receptor and growth hormone binding protein in rat liver nodules.

The growth hormone receptor (GHR) and growth hormone-binding protein (GH-BP) expression were characterized in liver nodules and hepatomas from male Wistar rats. The mRNA levels of GHR and GH-BP, studied by northern blot analysis and solution hybridization, were 35-50% (in nodules) and 2-6% (in hepatomas) of the level found in liver from untreated, age-matched rats. The binding of 125I-labeled human growth hormone to a low-density membrane fraction (LDMF) containing Golgi and endosome membranes in the presence of excess ovine prolactin was 75-80% lower in nodules than in liver. When endogenous ligand was removed, the binding increased in nodules but not in liver. Affinity cross-linking experiments revealed identical specific receptor-binding protein complexes at Mr of 95,000, 55,000, and 43,000 in both nodules and liver, assuming stochiometric binding of ligand. The in vivo endocytosis of 125I-labeled bovine growth hormone correlated with the level of GH binding and was thus reduced 75-80% in nodules, compared with liver. The level of insulin-like growth factor-I (IGF-I) mRNA was reduced by 50% in nodules; however, GH administration resulted in a twofold induction of IGF-I mRNA in both nodules and liver. It is concluded that the greater proportion of occupied GHR in nodules could result from an impaired dissociation of endogenous GH, which might explain the reduced GHR mRNA expression. Furthermore the low GHR mRNA expression may reflect a de-differentiated phenotype in nodules.

Animals↗

PubMed2003

Quantitative RT-PCR in cirrhotic nodules reveals gene expression changes associated with liver carcinogenesis.

Cirrhosis is considered to be the precursor of most hepatocellular carcinomas. To gain insight into the early molecular mechanisms of liver carcinogenesis, this study compared, using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), the expression levels of 31 selected genes in normal livers, cirrhotic nodules, and hepatocellular carcinomas. Since cirrhosis is composed of a mixture of polyclonal and monoclonal nodules, gene expression levels were also compared according to the clonal status of the cirrhotic nodules. The expression of eight of the 31 genes studied was significantly increased (NEGF2, ANGPT1, ARF, KRT19, SFN, CLDN4, MMP7, and ETV4) in cirrhotic nodules compared with normal liver, while only one was decreased (LYVE1). The same trend of variation was observed in cirrhosis and hepatocellular carcinomas for all of these genes except KRT19. When gene expression variation was compared according to the clonal status of cirrhotic nodules, only the LYVE1 expression level was significantly different. The LYVE1 gene expression level decreased progressively from polyclonal cirrhotic nodules to monoclonal cirrhotic nodules (polyclonal nodules 0.39 +/- 0.25; monoclonal nodules 0.20 +/- 0.14; p < 0.05) and to hepatocellular carcinoma (0.07 +/- 0.1). In conclusion, this study highlights the fact that among genes strongly dysregulated in hepatocellular carcinoma, some are already abnormally expressed in cirrhosis. The decrease in the expression level of one of these genes, LYVE1, was associated with monoclonality in cirrhotic nodules.

Adult↗

PubMed1993

Isolation and characterization of novel nodulin cDNAs representing genes expressed at early stages of soybean nodule development.

We took advantage of a subtractive hybridization procedure to isolate a set of cDNA clones of nodule-specific genes (nodulin genes) from developing soybean root nodules. Single-stranded 32P-labelled cDNA synthesized from nodule poly(A)+ RNA was hybridized with a large excess of uninfected root poly(A)+ RNA. Unhybridized cDNA was selected and used to screen nodule cDNA libraries. By this procedure we isolated several novel nodulin cDNA clones together with most of the nodulin cDNAs previously described. Four novel nodulin genes, which were expressed long before the onset of nitrogen fixation, were further characterized. GmN#36 and GmN#93 transcripts appeared in the roots less than 3 days after sowing and inoculation with Bradyrhizobium, but GmN#36 transcripts were also detected at very low levels in the stems of uninfected plants. Transcripts of GmN#315 and GmN#70 first appeared at 6-7 days, just before nodule emergence. Amino acid sequences of the predicted products of GmN#36, GmN#93 and GmN#70 exhibited no significant homology to proteins identified so far. The GmN#315 encoded protein has a limited but significant homology to some plant cyanins, suggesting that it is a metal-binding glycoprotein. In situ hybridization studies revealed that GmN#36 transcripts first appeared in the pericycle cells of the root stele near the infected site. During nodule emergence they were found in a few cell layers surrounding the vascular strands connecting the nodule meristem with the root stele, and in mature nodules they were present specifically in the pericycle cells in vascular bundles. These observations led us to hypothesize that GmN#36 gene products play a role in the transport and/or degradation of photosynthate. On the other hand, GmN#93 transcripts first appeared in the primary nodule meristem just below the root epidermis. In mature nodules they were only present in the infected cells.

Amino Acid Sequence↗

PubMed1981

Organ culture passage enhances the oncogenicity of carcinogen-induced hyperplastic mammary nodules.

The purpose of this study was to determine whether culturing hyperplastic mammary nodules in hormone-free medium would enhance their oncogenicity following subsequent transplantation into mammary fat pads. The underlying hypothesis is that the proliferation of transformed cells within the nodules is inhibited by hormone-dependent normal cells also present in the nodules. Accordingly, both primary hyperplastic nodules and tissues from a hyperplastic outgrowth of a primary nodule were maintained as organ cultures for varying periods in hormone-free Medium 199. The results show that whereas noncultured nodules developed mammary tumors at an incidence of only 15%, those passaged in organ culture gave rise to mammary tumors at an incidence of 40 to 43%. This threefold enhancement in the oncogenicity of mammary nodules is interpreted to be due, at least in part, to a reduction in the normal mammary cell content of nodules. Consistent with this interpretation is the observation that cultured nodules gave rise to mammary outgrowths that were predominantly hyperplastic, whereas noncultured nodules generated outgrowths with varying proportions of hyperplastic and normal ductal mammary tissue.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1999

Interleukin-1beta-induced release of matrix proteins into culture media causes inhibition of mineralization of nodules formed by periodontal ligament cells in vitro.

The mechanism by which interleukin-1beta (IL-1) inhibits the formation of mineralized tissue nodules by periodontal ligament (PDL) cells in vitro was investigated through the processes of morphological analysis, immunoprecipitation, and Northern blot analysis. PDL cells were obtained from a 2-day-old coagulum in tooth socket and cultured in Dulbecco's Modified Eagle Medium (DMEM) containing 10% fetal bone serum (FBS) and antibiotics. Confluent cells were grown for up to 3 weeks in the presence of ascorbic acid (AA), beta-glycerophosphate (GP), and dexamethasone (Dex), or IL-1. PDL cells cultured in the presence of GP and AA did not differentiate, but those treated with Dex, GP, and AA (Dex group) underwent differentiation, showing four stages (confluent, multilayer, nodule, and mineralization) of disparate morphological characteristics. In contrast, the cells treated with IL-1, Dex, GP, and AA (IL-1 group) did form multilayers but failed to form mineralized nodules. Electron microscopy demonstrated that the Dex-induced mineralized nodules contain multilayers of fibroblastic cells, numerous collagen fibrils, and dense globular as well as fused electron dense patches that are associated with numerous apatite crystals. The nodule-like structures in the IL-1 group were also comprised of multilayered fibroblastic cells, but they contained only a small number of collagen fibrils, and no dense globular or fused patches. Von Kossa staining confirmed the presence of numerous mineralized nodules in the Dex group and their scarceness in the IL-1 group. Northern blot analysis of IL-1-treated cells, however, revealed the presence of mRNAs for type I collagen (Col I), secreted protein, acidic and rich in cysteine (SPARC), osteopontin (OPN), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OC), whose expression patterns and levels were comparable to those of the Dex group. Immunoprecipitation analysis of OPN and BSP in the cell/matrix layers and the culture media after [35S]-methionine labeling showed their deposition primarily in the mineralized nodules of the Dex group, and their release into the media in the IL-1 group. Immunogold labeling demonstrated the location of OPN and BSP in mineralized nodules of the Dex group, but no significant labeling occurred in the nodule-like structures from the IL-1 group. Interestingly, IL-1 treatment increased the expression of collagenase mRNA by sevenfold, compared with that of the Dex group. These data suggest that the IL-1-induced formation of unmineralized nodules by PDL cells results not so much from the downregulated formation of matrix proteins, which plays a crucial role in the mineralization process, as from their release into the culture media. Finally, collagenase synthesis upregulated by IL-1 may be involved in this process.

Animals↗

PubMed2006

Endophytic occupation of root nodules and roots of Melilotus dentatus by Agrobacterium tumefaciens.

Agrobacterium strains have been frequently isolated from the root nodules of different legumes. Various possible mechanisms have been proposed to explain the existence of these bacteria in nodules, but there is no sufficient experimental evidence to support the estimations. In this work, we proved that the Agrobacterium strain CCBAU 81181, which was originally isolated from the root nodules of Onobrychis viciaefolia, and a symbiotic strain of Sinorhizobium meliloti CCBAU 10062 could coinhabit the root nodules of Melilotus dentatus. Analyses were performed by using a fluorescence marker, reisolation of bacteria from nodules, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of whole cellular proteins, and polymerase chain reaction amplification of symbiotic genes. The inoculation of A. tumefaciens CCBAU 81181 did not affect the growth and nodulation of plants. CCBAU 81181 and 24 other Agrobacterium strains isolated from nodules were incapable of nodulating on their original or alternative host and 22 strains of these strains were endophytes in the roots and stems of their hosts. Also, the tumor-inducing A. tumefaciens strains IAM 13129(T) and C58 were found capable of entering the roots of Glycyrrhiza pallidiflora, but did not cause pathogenic symptoms. With these results, we conclude that A. tumefaciens strains could be endophytic bacteria in the roots, stems, and root nodules. This finding partially explains why Agrobacterium strains were frequently isolated from the surface-sterilized nodules.

Agrobacterium tumefaciens↗

PubMed1994

Clonal analysis of regenerative nodules in hepatitis C virus-induced liver cirrhosis.

BACKGROUND/AIMS: Based on histological criteria, regenerative nodules in cirrhotic liver have been generally considered to result from hyperplastic proliferation of hepatocytes. Whether these nodules are hyperplastic or neoplastic has not been determined definitively. This study examined the issue by clonal analysis of each nodule. METHODS: The method for clonal analysis was based on restriction fragment length polymorphism of the X chromosome-linked phosphoglycerokinase gene and on random inactivation of the gene by methylation. RESULTS: Clonality of hepatocellular carcinoma (n = 7) and regenerative nodules (n = 76) induced by hepatitis C virus infection was analyzed. All carcinomas were monoclonal. Clonal analysis of regenerative nodules showed that 43% (33 of 76) were monoclonal in origin. Adjacent monoclonal nodules showed inactivation of the same allele of phosphoglycerokinase gene. Because the gene allele is inactivated at random, it is unlikely that each nodule happens to inactivate the same allele; it is more likely that monoclonal cell expansion is initiated before the nodule is established by septum formation. CONCLUSIONS: Monoclonal cell expansion is seen in a considerable number of regenerative nodules in cirrhotic liver. The results indicate that certain genetic changes, which are required for hepatocarcinogenesis, have already occurred in these nodules.

Base Sequence↗

PubMed1993

Focal mesangiolysis and the pathogenesis of the Kimmelstiel-Wilson nodule.

Kidneys from 74 consecutively autopsied primarily non-insulin-dependent diabetes cases and 59 age-, sex-, and ethnic group-matched controls were examined qualitatively and semiquantitatively to determine whether focal mesangiolyses (FMs), Kimmelstiel-Wilson (KW) nodules, and glomerular capillary microaneurysms (GCMs) were related lesions, to determine their extent and pathogenic sequence, and to look for associations with structural and functional factors. Light microscopic examination of serial sections, immunohistochemical stains, image analysis, and electron microscopy were used. Focal mesangiolyses, KW nodules, and GCMs occurred in 31 of the 74 diabetes cases (27 had FMs, 29 had KW nodules, and nine had GCMs) and were positively correlated with each other semiquantitatively (r = .71, .70, and .68, respectively). Numerous FMs were found, involving 62% and 78% of the glomeruli in the two most severely affected cases. Most FMs were located at the periphery of KW nodules, but de novo FMs were documented in six cases. Glomerular capillary microaneurysms were deemed occasional complications of FMs because they were much less common, and 25 of the 27 GCMs identified were contiguous with FMs. Focal mesangiolyses and GCMs were deemed transient lesions, being absent in end-stage kidneys. Both FMs and KW nodules consisted of a spectrum of lesions. For the sake of clarity they were arbitrarily divided into two types: edematous and proliferative FMs and simple and complicated KW nodules. Their characteristics suggested the following pathogenic sequence: edematous FM-->proliferative FM-->focal nodular mesangial expansion-->simple KW nodule-->recurrent FM-->complicated KW nodule. Complicated nodules were associated with marked alterations in the lobular capillary. The number of mesangial cells was increased in FMs and they were thought to be responsible for increased matrix production. Focal mesangiolyses and KW nodules were positively associated with diabetes, proteinuria, and hyalinization of afferent and efferent arterioles, but were weakly or not associated with hypertension, arcuate and interlobular artery stenosis, hydroenphrosis, acute pyelonephritis, renal arterial atheromatous emboli, glomerular platelet-fibrin thromboemboli, and congestive heart failure.

Autopsy↗

PubMed1984

Effect of phenobarbital on the altered biochemical phenotypes expressed by hyperplastic liver nodules during hepatocarcinogenesis in the rat.

The effects of a chronic 8- to 12-week administration of the hepatic tumor promoter, phenobarbital, on further altering the biochemical enzyme deviation patterns shown by hyperplastic liver nodules was examined in rats previously subjected to the initiation/selection protocol of Solt and Farber. Hyperplastic liver nodules of various size classes from the phenobarbital-treated group exhibited a significant increase in GGT specific activity, as well as 2- to 3-fold higher levels of microsomal cytochrome P-450 than was shown by control nodules. The increase in GGT specific activity was also found in many cases to be higher in those hyperplastic liver nodules from the phenobarbital-treated group with diameters greater than 3.0-3.5 mm than in nodules of a smaller size. In contrast, the GGT specific activity of the control nodules did not correlate with differences in their sizes. Furthermore, while histochemical staining of GGT activity appeared uniform in sections of the various sized hyperplastic nodules from the phenobarbital-treated group, biochemical measurements indicated a consistently higher specific activity for this enzyme in tissue taken from the central portion of the nodule than in tissue from the peripheral portion of the nodule. On the other hand, the specific activities of glucose-6-phosphatase, 5'-nucleotidase, and fructose-1,6-diphosphate aldolase of the hyperplastic liver nodules were not found to be significantly altered over control values by the chronic phenobarbital treatment, suggesting a stability of these other marker enzyme alterations during the early promotional phase of hepatocarcinogenesis.

Animals↗

PubMed1997

Seryl-phosphorylation of soybean nodule sucrose synthase (nodulin-100) by a Ca2+-dependent protein kinase.

Sucrose synthase (SS; EC 2.4.1.13) was radiolabeled in situ by incubating detached soybean nodules with 32Pi. Phosphoamino acid analysis indicated that SS was phosphorylated on a serine residue(s). In-vitro phosphorylation of purified nodule SS by desalted nodule extracts was Ca2+-dependent. This SS-kinase was partially purified (approximately 2200-fold) from nodules harvested from illuminated plants. The molecular mass of the SS-kinase was about 55,000 on a Superdex 75 size-exclusion column or in a denaturing autophosphorylation gel. With either purified nodule SS or Syntide 2 as substrate, exogenous calmodulin and phosphatidylserine showed little or no effect on the in-vitro activity of this partially purified protein kinase. However, its activity was inhibited by W-7. The purified nodule SS-kinase (or CDPK) phosphorylated nodule PEP carboxylase (PEPC; EC 4.1.1.31) in the presence of Ca2+. In contrast, a partially purified nodule PEPC-kinase preparation was incapable of phosphorylating nodule SS. Unlike nodule PEPC [Zhang et al. (1995) Plant Physiol. 108, 1561-1568], the phosphorylation state of SS is not likely modulated in planta by photosynthate supply from the shoots.

Glucosyltransferases↗