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Ultrasound-guided fine-needle aspiration biopsy of thyroid nodules and multinodular goiters.

OBJECTIVE: To describe various techniques for performing ultrasound-guided fine-needle aspiration (FNA) biopsy of thyroid nodules, with the intent of shortening the learning curve for physicians with interest in this new procedure. METHODS: General principles and details of biopsy techniques and equipment are reviewed, and personal experience and preferences are described. RESULTS: Real-time ultrasound guidance has technically refined the FNA biopsy technique by decreasing the number of inadequate biopsy specimens and increasing both the specificity and the sensitivity of this procedure. In addition to being cost-effective, well tolerated, and expedient, ultrasound-guided FNA biopsy has emerged as the most accurate method for evaluation of thyroid nodules. The success of the procedure depends on the experience of the person using these techniques. CONCLUSION: For provision of optimal evaluation and management of thyroid nodules, endocrinologists should develop expertise in ultrasound-guided FNA biopsy and understand its advantages over conventional FNA biopsy.

Biopsy, Fine-Needle↗

Cellular biochemistry of the stepwise development of cancer with chemicals: G. H. A. Clowes memorial lecture.

The sequence of possible cellular, tissue, biochemical, and molecular changes that are important during the development of experimental liver cancer with chemicals is reviewed from the viewpoint of the author's experience in carcinogenesis over the past 25 years. The development of a new model for the analysis of liver carcinogenesis, the resistant hepatocyte model, is briefly described, as are the known steps between exposure to an initiating dose of a chemical carcinogen to the appearance of hepatocellular carcinoma. These steps include: (a) the interactions with DNA; (b) the dependence on a round of cell proliferation for initiation; (c) one type of initiated hepatocyte, a resistant hepatocyte; (d) the selection of these new hepatocytes, probably by clonal expansion, to form synchronously the first type of hepatocyte nodules, early nodules; (e) the election of the majority of these nodules to undergo remodeling to normal-appearing liver by differentiation ("redifferentiation"); (f) the election of a minority of early nodules to persist; (g) the slow growth of the few persistent nodules; and (h) the precursor role of persistent nodules in the development of hepatocellular carcinoma. The evidence for such a precursor role includes: (a) the common occurrence in persistent nodules of a subsequent precancerous step, "nodules in nodules"; (b) the occurrence of metastasizing cancer inside nodules without cancer elsewhere in the liver; and (c) the high rate of evolution to cancer of persistent nodules, but not of early nodules, when transplanted to the spleen. Based on the common architecture, organization, blood supply, and biochemical pattern of properties relating to the metabolism of xenobiotics in hepatocyte nodules in six different models of liver carcinogenesis and on the common occurrence of a highly programmed redifferentiation pattern of carcinogen-induced hepatocyte nodules, it is concluded that heterogeneity and diversity seen in many phenotypic properties of cancers, including liver cancers, is preceded by a precursor population that is unusually homogeneous and uniform in phenotype. Thus, the heterogeneity and diversity of cancers are probably late manifestations in carcinogenesis. The available evidence is very suggestive that the hepatocyte nodules are an expression of physiological adaptation to exposure to hazardous xenobiotics and not a form of aberration or mutation. The data also suggest that hepatocyte nodules are an additional pattern of liver differentiation and that liver cancer, to be understood, should be compared with this precursor new state rather than the conventional adult, fetal, or embryonic states.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Partitioning of C-photosynthate, and long distance translocation of amino acids in preflowering and flowering, nodulated and nonnodulated soybeans.

The influence of stage of development (preflowering versus flowering) in nodulated and nonnodulated soybeans (Glycine max [L.] Merr. cv. Wells) on partitioning of (14)C into assimilates following exposure of a soybean leaf to (14)CO(2) by both steady-state and pulse-labeling techniques was studied. Blades on the second fully expanded leaf from the stem apex were exposed to (14)CO(2). Radioactive assimilates were extracted from source leaf blades, petioles, and stems (both the path up and path down from source leaf), were separated into neutral (sugars), basic (amino acids), and acidic (organic acids, sugar phosphates) fractions by ion exchange chromatography. The basic fraction was further resolved using thin layer chromatography and the percentage of radioactivity recovered in each amino acid was determined.The distribution of radioactivity in the neutral, basic, and acidic fractions of the source leaf blades was significantly different from that of the transport path (petiole and stems). About 70% of the radioactivity in source leaf blades was recovered in the neutral fraction, whereas about 90% of the recovered radioactivity in the path was in the neutral fraction. (14)C-Aminoacids constituted 8 to 17% and 2 to 7% of the recovered radioactivity in source leaves and paths, respectively. Recovered (14)C in organic acids ranged from 13 to 20% and 2 to 7% in source leaves and paths, respectively. Partitioning of (14)C-assimilates among the neutral, basic, and acidic fractions was not affected by the presence of nodules or flowers. However, when steady-state labeling was compared to pulse labeling, a significantly lower percentage of (14)C was recovered in the neutral fraction with a concomitant increase in the basic fraction. Asparagine-arginine, serine, glutamate, gamma-aminobutyrate-alanine, and aspartate accounted for 69 to 85% of the recovered radioactivity in the basic fraction from the various treatments. [(14)C]Serine was significantly higher in pulse-labeling experiments, whereas glutamtate and proline were higher with steady-state labeling. [(14)C]Serine was significantly higher in nonnodulated plants than in nodulated plants, whereas gamma-aminobutyrate-alanine was significantly higher in preflowering plants as compared to flowering plants.

Journal Article↗

Molecular diversity of rhizobia nodulating the invasive legume Cytisus scoparius in Australia.

AIMS: To contribute to the understanding of Cytisus scoparius success at invading and establishing itself in Australia. METHODS AND RESULTS: Root-nodule bacteria isolated from C. scoparius, growing on five different sites and originally introduced to Australia, were compared with isolates from indigenous plants growing in France and isolates from native legumes growing on the same Australian sites as C. scoparius. Small-subunit rDNA from 251 isolates were analysed by PCR-RFLP and representatives from different genospecies were selected for sequencing. Phylogenetic analyses revealed a great diversity of lineages belonging to Bradyrhizobium, with one genospecies being specific for Cytisus both in Australia and in France, Rhizobium and Mesorhizobium and one falling outside the described genera of legume-nodulating bacteria. Principal component analysis showed that the Cytisus Australian rhizobial communities are more similar to each other than to their co-occurring native partners. CONCLUSIONS: Early established rhizobial symbionts may have an increased probability to contribute inoculum for the development of further nodules. SIGNIFICANCE AND IMPACT OF THE STUDY: This is a first report comparing rhizobia nodulating C. scoparius in its native and exotic environments. Cytisus scoparius symbionts were identified outside the Bradyrhizobium genus and a new lineage of legume-nodulating bacteria was identified.

Australia↗

Significance of non-calcified pulmonary nodules in patients with extrapulmonary cancers.

BACKGROUND: This study sought to determine the rate and patterns of malignancy in patients with extrapulmonary cancers and non-calcified pulmonary nodules, and to develop a statistical model to guide clinicians regarding choice of patients for diagnostic biopsy. METHOD: The medical records of 151 patients evaluated at the Memorial Sloan-Kettering Cancer Center between January 1999 and December 2001 for non-calcified pulmonary nodules were reviewed. Nodules were considered malignant based on the results of a diagnostic biopsy, and were considered benign if their appearance remained stable 2 years after the initial study, if they resolved, or if a biopsy showed a non-malignant condition. RESULTS: Sixty four of 151 patients (42%) were diagnosed with malignant nodules; 32 had newly diagnosed lung cancers, 28 had metastatic spread of their primary cancers, and four had lesions that were either new cancers or of undetermined aetiology. On univariate analysis the likelihood of malignancy increased with nodule size, tobacco exposure, and the finding of a solitary nodule. On multivariable analysis only nodule size and tobacco exposure were predictive of malignancy. The model had good predictive accuracy (area under the curve 0.751) but had insufficient discrimination for use as a clinical tool to determine which patients should undergo diagnostic biopsy. CONCLUSION: Nearly half the non-calcified pulmonary nodules identified in this series were malignant. Lung cancer was more common than metastatic disease. These findings support the need for close interval follow up and a low threshold for diagnostic biopsy in patients with extrapulmonary cancers and non-calcified pulmonary nodules. In smokers, such lesions should raise concern for lung cancer.

Aged↗

Low-energy laser irradiation stimulates bone nodule formation at early stages of cell culture in rat calvarial cells.

Although the acceleration of bone regeneration by laser treatment has been reported, the mechanisms of action of laser on bone are unclear. To determine the target cells responsible for the action of laser irradiation and roles of irradiation on these cells during bone formation, we investigated the effects of low-energy laser irradiation at various cell culture stages on cellular proliferation, bone nodule formation, alkaline phosphatase activity, and osteocalcin gene expression, employing rat calvarial cells. Osteoblast-like cells isolated from fetal rat calvariae were irradiated once with a low-energy Ga-Al-As laser (830 nm, 500 mW) at various cell culture stages (days 1-16). Laser irradiation at early stages of culture significantly stimulated cellular proliferation, ALP activity, and osteocalcin gene expression thereafter. Furthermore, laser irradiation at earlier stages of culture significantly stimulated a greater number (1.7-fold) and larger area (3.4-fold) of bone nodules that had developed in the culture dish on day 21. However, these effects could not be found by irradiation at a later date. These results suggest that laser irradiation may play two principal roles in stimulating bone formation. One is stimulation of cellular proliferation, especially proliferation of nodule-forming cells of osteoblast lineage, and the other is stimulation of cellular differentiation, especially to committed precursors, resulting in an increase in the number of more differentiated osteoblastic cells and an increase in bone formation. Both bone-formation-stimulating roles may be exhibited by laser irradiation to immature cells only.

Alkaline Phosphatase↗

Fatal hemothorax due to rupture of an intrathoracic extramedullary hematopoietic nodule.

Intrathoracic extramedullary hematopoiesis (TEMH) is an unusual but well-described entity, which is typically found in patients who have chronic hemolytic anemias, myelofibrosis, or myeloproliferative disorders. It is seldom symptomatic, rarely fatal. We report a case of a 26-year-old African-American male with a past medical history of sickle cell trait/beta thalassemia who developed multiple intrathoracic nodules of extramedullary hematopoiesis. One of these nodules spontaneously ruptured and produced a fatal hemothorax.

Adult↗

Head and neck irradiation in childhood: increased risk of developing thyroid disease.

A nodule of the thyroid in a patient with a history of prior irradiation to the head and neck area in childhood is more likely to be malignant than a nodule in the general population. Thirty-two of 144 such patients (22%) who came to surgery were found to have a carcinoma of the thyroid. A relative short-term (6 mo) trial with suppressive therapy with a thyroactive agent may be helpful in selecting out those nodules that may be malignant. Although considerable controversy continues to exist as to the proper surgical treatment, our current surgical management involves performing a total extracapsular thyroidectomy.

Child↗

Enhancement by Wy-14,643, a hepatic peroxisome proliferator, of diethylnitrosamine-initiated hepatic tumorigenesis in the rat.

Diethylnitrosamine (DEN), at a concentration of 100 parts/10(6) in drinking water for 14 days, caused the development, by 48 weeks, of very few liver tumours in 5 of 18 (27%) male F=344 rats fed control diet. When the DEN treatment was followed one week later by continuous feeding of the hypolipidemic hepatic peroxisome proliferator, Wy-14,643, at 0.1% dietary level, all of 28 rats (100%) developed, between 38 and 48 weeks, a significantly higher number of liver tumours. Furthermore, laparotomy at 22 weeks revealed that several rats fed Wy-14,643 after DEN initiation had developed visible liver nodules, suggesting that Wy-14,643 also accelerates the appearance of these tumours. Administration of another peroxisome proliferator, clofibrate, at 0.5% level in the diet after DEN initiation, also caused a substantial enhancement of liver tumorigenesis. The enhancement of liver-tumour development by clofibrate, however, was less than that by Wy-14,643. The marked enhancing effect of Wy-14,643 may be due to its profound hepatomegalic and peroxisome proliferative properties.

Acetates↗

Development of Bacteroids in Alfalfa (Medicago sativa) Nodules.

The morphology, acetylene reduction capability, and nucleic acid content of bacteroids in different regions of alfalfa (Medicago sativa var. Buffalo) nodules were studied by electron microscopy, gas chromatography, and laser flow microfluorometry, respectively. Bacteroids in the nodule tips were small (1 to 2.5 micrometers in length), had low nucleic acid content, and contained distinct central nucleoids. These bacteroids were comparatively inactive in acetylene reduction in situ. Bacteroids in the middle regions of alfalfa nodules were greatly enlarged (5 to 7 micrometers in length), had relatively high nucleic acid content, and did not possess central nucleoids. The bacteroids were very active in acetylene reduction. Bacteroids in the basal nodule region also were enlarged and without distinct nucleoid regions, but had relatively low nucleic acid content and low in situ acetylene-reducing activity.

Journal Article↗

SV40 in human thyroid nodules.

BACKGROUND: Simian virus 40 (SV40) has been a model experimental system for the study of cell transformation and tumorigenesis for many years. The study of SV40 in humans has aroused interest in the related BK virus (BKV) and JC virus (JCV) and their role in human disease. OBJECTIVES: SV40 has been found in a variety of human samples, both malignant and normal. Many independent studies have suggested that SV40 plays a role for some cancers. However, in most cases the role of SV40 remains unclear. STUDY DESIGN: The subject of this study consisted of 99 patients with thyroid nodules. Both thyroid nodule and normal thyroid tissue were taken from each patient to test whether they contained SV40 sequences. RESULTS: We detected SV40 sequences by polymerase chain reaction (PCR) in four of 99 thyroid nodules. Two of them were papillary thyroid carcinomas and the others were benign thyroid nodules. No SV40 was detected in 99 of normal thyroid tissues of the same patients. DNA sequence analysis, performed in four positive samples, confirmed that PCR products belong to the SV40 T antigen (Tag) region. CONCLUSION: The possible role of SV40 in the development of thyroid nodules and the spread of SV40 by horizontal infection in the human population are discussed.

Adolescent↗

Sucrose synthase in legume nodules is essential for nitrogen fixation

The role of sucrose synthase (SS) in the fixation of N was examined in the rug4 mutant of pea (Pisum sativum L.) plants in which SS activity was severely reduced. When dependent on nodules for their N supply, the mutant plants were not viable and appeared to be incapable of effective N fixation, although nodule formation was essentially normal. In fact, N and C resources invested in nodules were much greater in mutant plants than in the wild-type (WT) plants. Low SS activity in nodules (present at only 10% of WT levels) resulted in lower amounts of total soluble protein and leghemoglobin and lower activities of several enzymes compared with WT nodules. Alkaline invertase activity was not increased to compensate for reduced SS activity. Leghemoglobin was present at less than 20% of WT values, so O2 flux may have been compromised. The two components of nitrogenase were present at normal levels in mutant nodules. However, only a trace of nitrogenase activity was detected in intact plants and none was found in isolated bacteroids. The results are discussed in relation to the role of SS in the provision of C substrates for N fixation and in the development of functional nodules.

Journal Article↗

Proteolysis during Development and Senescence of Effective and Plant Gene-Controlled Ineffective Alfalfa Nodules.

Plant-controlled ineffective root nodules, conditioned by the in1 gene in Medicago sativa L. cv Saranac, undergo premature senescence and have reduced levels of many late nodulins. To ascertain which factors contribute to premature senescence, we have evaluated proteolysis as it occurs throughout the development of ineffective Saranac (in1Sa) and effective Saranac nodules. Cysteine protease activities with acidic pH optimum and enzyme proteins were present in both genotypes. We found that acidic protease activity was low in effective Saranac nodules throughout their development. In contrast, by 2 weeks after inoculation, acid protease activity of in1Sa nodules was severalfold higher than that of Saranac nodules and remained high until the experiment was terminated 8 weeks later. This increase in protease enzyme activity correlated with an increase in protease protein amounts. Increased protease activity and amount in in1Sa nodules was correlated with a decrease in nodule soluble protein. The time at which in1Sa nodules initially showed increased protease activity corresponded to when symbiosis deteriorated. High levels of phosphoenolpyruvate carboxylase (PEPC) protein were expressed in effective nodules by 12 d after inoculation and expression was associated with low proteolytic enzyme activity. In contrast, although PEPC was expressed in in1Sa nodules, PEPC protein was not found 12 d after inoculation and thereafter. Acidic protease from in1Sa nodules could also degrade purified leghemoglobin. These data indicate that premature senescence and low levels of late nodulins in in1Sa nodules can be correlated in part with increased proteolysis.

Journal Article↗

Cutaneous myelofibrosis.

Cutaneous extramedullary hematopoiesis is rare, usually occurring in neonates following intrauterine viral infections, hereditary spherocytosis, or the twin transfusion syndrome. Only 20 cases of cutaneous extramedullary hematopoiesis have been reported in adults, all with myelofibrosis. The cutaneous infiltrates may be atypical and difficult to distinguish from leukemia cutis. We have studied a 65-year-old woman with myelofibrosis and approximately 40 violaceous, firm, non-tender cutaneous nodules measuring 1 to 4 cm in diameter, located on her abdomen near a splenectomy scar. Histologically, the lesions had a dense infiltrate of myeloid cells in all stages of maturation, atypical large cells with multilobate nuclei or multiple nuclei, resembling atypical megakaryocytes, and fibroblasts. Although the patient received erythropoietin therapy prior to the development of the nodules, erythroid progenitors were not seen. Reticulin was increased particularly surrounding the atypical megakaryocytes. The myeloid cells stained for chloroacetate esterase and with the polyclonal antibody MAC 387. Atypical megakaryocytes stained for Factor XIIIa and Factor VIII-related antigen. Dendritic Factor XIIIa positive cells were also increased. The skin lesions remain unchanged grossly one year after their development.

Aged↗