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Proposed panel of diagnostic criteria, including the use of ultrasound, to refine the concept of 'endemic normals' in lymphatic filariasis.

Although living adult Wuchereria bancrofti worms can be detected by ultrasound examination of the scrotal area in approximately 80% of men infected with this filarial parasite, the location of the adult worms in the remaining 20% remains unclear. To determine this, 32 individuals who had W. bancrofti microfilaraemia but no adult worms detectable on ultrasound were treated with diethylcarbarmazine (DEC), either with a single 6 mg/kg dose (n = 13) or with a 12-day course of 6 mg/kg per day (n = 19). They were then monitored with serial physical and ultrasound examinations. Thirteen (41%) subjects developed small, single scrotal nodules 12 h to 7 days after treatment; this rate was unaffected by the dose of DEC. No nodules were detected outside the scrotal area. All 5 men with lymphangiectasia suspected on ultrasound before treatment developed scrotal nodules, compared to 8 (29.6%) of 27 men without ultrasonographic evidence (P = 0.006). Thus, using both ultrasound and 'provocative' treatment with DEC, adult W. bancrofti can be detected in the scrotal area of an estimated 88% of infected men. Because no single diagnostic test for W. bancrofti infection is completely sensitive, a panel of tests, including ultrasound, is proposed to identify with greater accuracy 'endemic normals' for immunological and epidemiological studies.

Adult↗

Thyroid nodules in female uremic patients on maintenance hemodialysis.

We investigated the incidence of thyroid nodules in female uremic patients on maintenance hemodialysis using a high-frequency sonographic scanner. In 47 (21.0%) of the 224 female normal controls and 33 (55.0%) of the 60 female patients, thyroid nodules were detected. The difference in these incidences between controls and patients was significant. There were no differences in age, duration of hemodialysis, the level of blood urea nitrogen, parathyroid hormone or thyroid stimulating hormone between the patients with thyroid nodules and those without nodules. Although there is a correlation between uremia and the development of thyroid nodules, the details of the underlying mechanism of their association remain unclear.

Adult↗

Carcinogen-induced alteration in liver epidermal growth factor receptor distribution during the promotion stage of hepatocarcinogenesis in rat.

Changes in hepatic membrane binding capacity for epidermal growth factor (EGF) were assessed during 2-acetylaminofluorine (2-AAF)-induced hepatocarcinogenesis. An overall decrease in membrane EGF binding levels was observed throughout the period of 2-AAF administration. Immunochemical studies indicated the decreases in EGF binding levels were paralleled by decreases in tissue EGF receptor levels. Immunohistochemical studies showed that the losses in hepatic EGF receptor levels were not uniform throughout the liver during the early, promotion stage of cancer development. During the promotion stage, preneoplastic liver nodules were found to display a higher level of EGF receptor than surrounding hepatic tissue. This resistance to 2-AAF-mediated down-regulation of EGF receptor may confer a proliferative advantage to the developing nodule relative to the surrounding liver tissue. Similar immunochemical and immunohistochemical analysis of hepatocarcinomas at late stages of 2-AAF-induced hepatocarcinogenesis indicated a uniform loss of EGF receptor in tumor and surrounding tissue. These studies indicate that carcinogen-mediated changes in EGF binding levels are different during the multistage process of hepatocarcinogenesis, and that resistance to down-regulation of EGF receptor among preneoplastic nodules may have a role in providing a selective growth advantage to initiated cell populations. EGF receptor may be useful as a dynamic marker assessing the development of hepatic tumors.

2-Acetylaminofluorene↗

Reduction of pain and local complications when buffered lidocaine solution is used as a local anesthetic in conjunction with hyperthermia treatments: results of a randomized trial.

Unbuffered lidocaine (pH = 6.5) is commonly employed as a local anesthetic prior to transcutaneous placement of catheters for use in temperature monitoring during hyperthermia treatments. The most frequent complaint associated with this procedure is stinging or burning pain at the injection site. Tender firm subcutaneous nodules at sites of lidocaine infiltration for catheter placement have also been noted in fields treated with radiation and hyperthermia. A reduction in the pain associated with lidocaine infiltration has been reported by the use of alkalinized (buffered) local anesthetic solutions. To confirm this finding in patients treated with hyperthermia for superficially-located tumors, a randomized prospective double blind trial comparing unbuffered (pH 6.5) and buffered (pH 7.3) 2% lidocaine (without epinephrine) was undertaken. Between March and October 1990, a total of 54 hyperthermia treatment fields were each randomized to buffered or unbuffered lidocaine to be used at the time of all catheter placements (146 placements). Patients were scored both for the pain noted during the infiltration of lidocaine and the pain noted with subsequent catheter placement. In addition, the development of subcutaneous nodules at the sites of catheter placement was monitored at the time of 3-week follow-up. Follow-up was available for all but two fields. Treatment fields that received the buffered anesthetic had a statistically significant reduction in the pain associated with infiltration of lidocaine (p less than 0.05) without any compromise in its therapeutic efficacy as observed on a linear Visual Analog Scale. Furthermore, the incidence of subcutaneous nodules was lower in the fields treated with the buffered solution (1/23 vs 7/29, p = 0.05 for buffered and unbuffered solutions, respectively). The results of this trial support the use of buffered lidocaine prior to catheter placement for hyperthermia treatments as a method of reducing pain at infiltration and the subsequent development of subcutaneous nodules.

Buffers↗

Thickening and nodules in port-wine stains.

Port-wine stains are vascular ectasias that can develop thickening or nodules over time. Thickening is a further dilation of the ectatic vessels, and nodules are vascular neoplasms or hyperplasias. The records of 173 subjects with port-wine stains were reviewed for thickening, nodules, and associated characteristics. The incidence of nodules increased with age. Thickening often began in early adulthood, but its intensity and association with nodules continued to increase into older age. Thickening and nodules were most common in the area of the second and third branches of the trigeminal nerve innervating the face and were associated with deepening color. The incidence of thickening alone was greater in male than in female patients.

Adolescent↗

Cellular atypia in a rheumatoid nodule: a diagnostic pitfall of aspiration biopsy.

A 63-year-old cachectic white male developed subcutaneous scalp nodules. Clinically these were felt most likely to represent metastatic tumor, although the patient was known to have rheumatoid arthritis. Aspiration cytology was interpreted as malignant due to the presence of atypical cells, but tissue biopsies demonstrated necrotizing palisading granulomas. The diagnostic hazard of cellular atypia in rheumatoid nodules is discussed.

Biopsy, Needle↗

Serum factor levels during the growth of rat hepatoma nodules in the lungs.

The levels of tumour-specific antigen, antibody and specific immune complexes in the sera of rats bearing lung nodules of a chemically induced rat hepatoma, produced by intravenous inoculation of viable tumour cells, have been examined and compared with the levels of serum factors in animals actively immunized by intravenous inoculation of mixed tumour cells and BCG. Animals inoculated with cells alone developed multiple lung nodules which slowly grew, until on day 24 the remaining animals had to be killed due to respiratory distress. In contrast, the animals receiving a mixed inoculum of BCG and tumour cells developed no visible lung nodules and were capable of rejecting a further challenge of tumour cells. Tumour-specific antigen could be detected in the sera of both groups of rats at different times. In actively immunized animals free antigen could be detected from day 3 to day 10 after inoculation of cells BCG whereas in animals receiving cells alone, free antigen could not be detected until day 14 and persisted until the termination of the experiment. Free tumour-specific antibody, however, was found in the sera of rats actively immunized with tumour cells and BCG from day 10 onwards, although in the other group of animals it could not be detected. Conversely, immune complexes of tumour-specific antigen and antibody could be detected from day 10 in rats receiving cells alone and only at day 10 in actively immunized rats. The relevance of these findings in relation to what is known about serum factor levels during tumour growth and regression is discussed.

Animals↗

Hepatic stellate cell activation in dysplastic nodules: evidence for an alternate hypothesis concerning human hepatocarcinogenesis.

We have previously suggested that dysplastic nodules (also referred to as "adenomatous hyperplasia" or "macroregenerative nodules"), likely precursors of hepatocellular carcinoma (HCC), develop as an infiltrating clonal expansion, in advance of or parallel to cirrhosis. As part of this hypothesis, to explain aspects of their gross and microscopic appearance, we suggested that dysplastic nodules are resistant to the scarring process affecting the rest of the liver. We sought to test this hypothesis by examining the distribution of activated hepatic stellate cells (HSCs), the hallmark of hepatic scarring, in cirrhotic nodules, dysplastic nodules and HCC. We immunohistochemically stained 56 cirrhotic nodules, 20 low grade dysplastic nodules, 27 high grade dysplastic nodules, and 20 HCCs with monoclonal antibodies against alpha-smooth muscle actin to identify activated HSCs. Distribution and number of HSCs were graded semiquantitatively (0 to 4+). In our results, HSCs were significantly less widespread in dysplastic nodules than in cirrhotic nodules or in HCCs (both: p < 0.00001). HSCs were also more prominent in the periphery of dysplastic nodules than in the center, though still fewer in number than in cirrhotic nodules. In conclusion, the low number of activated HSCs in dysplastic nodules, compared to both cirrhotic nodules and HCC, supports our hypothesis concerning dysplastic nodule development: that they arise as clonal expansions of neoplastic hepatocytes in advance of, or parallel to, the development of cirrhosis.

Actins↗

Regulation of Nodulation by Rhizobium meliloti 102F15 on Its Mutant Which Forms an Unusually High Number of Nodules on Alfalfa.

A mutant (WL3A150) of Rhizobium meliloti 102F51 that elicits an unusually high number of nodules on its host, alfalfa (Medicago sativa), supports the idea that the host may rely on early bacteroid development in the nodule or on metabolites produced in the infection thread as one of the signals to control further nodulation. This mutant was initially isolated because of its Fix phenotype. It consistently formed many more nodules than all the other Fix mutants isolated from strain 102F51 (a total of 11 mutants). Nodules formed by this mutant were small and white and were indistinguishable in appearance from nodules formed by the other Fix mutants. An ultrastructural study of the nodules, however, showed that this mutant, although forming numerous infection threads, failed to develop into bacteroids. The ability of the mutant to form an unusually high number of nodules coulde be suppressed in a time-dependent manner by the presence of the wild type.

Journal Article↗

Multistep and multicentric development of hepatocellular carcinoma: histological analysis of 980 resected nodules.

BACKGROUND/AIMS: Histological observations support the concept of multistep and multicentric development of hepatocellular carcinoma (HCC) in cases of chronic liver disease. However, the relationship between the incidence of such a modality of development of HCC and the type of background liver disease has not been fully investigated. METHODS: A total of 980 HCC nodules resected from 664 patients were analyzed. Multistep HCC was defined as well differentiated HCC containing the portal tracts (early HCC), or the presence of early HCC-like areas in the periphery of the nodule. In cases with multiple nodules, if the smaller nodule showed the features of multistep HCC, or if each nodule showed a distinct histology, the case was defined to have multicentric HCC. RESULTS: Of the 980 nodules, 369 (37.7%) met the criteria of multistep HCC. Of the 664 patients, 177 (26.7%) had multiple nodules that met the criteria of multicentric HCC. Both the incidences of multistep and multicentric HCC were significantly higher in HCV-Ab-positive cases than in HBs-Ag-positive cases (46.0 vs. 19.1%, P<0.001 and 34.1 vs. 16.5%, P=0.005, respectively). CONCLUSIONS: Multistep and multicentric HCC develops most frequently in patients with HCV infection.

Carcinoma, Hepatocellular↗

Increased hepatic androgen receptor expression in female rats during diethylnitrosamine liver carcinogenesis. A possible correlation with liver tumor development.

This study investigated the relationship between liver tumor development and androgen-receptor expression in diethylnitrosamine hepatocarcinogenesis in Wistar rats (SUAH substrain). Random liver samples were assayed by an isoelectric focusing method, with [3H]mibolerone as androgenic radioligand. After 16 wk of oral diethylnitrosamine treatment there was a greater than 20-fold increase in hepatic androgen receptor concentration in female rats (control group 0.3 +/- 0.07 fmol/mg cytosol protein; test group 8.36 +/- 0.96 fmol/mg cytosol protein; p less than 0.001, unpaired Student's t-test). This coincided with, and may be related to, an accelerated development of neoplastic nodules or hepatocellular carcinoma, or both. Male rats showed slower tumor development and no change in androgen receptor concentrations. This model is the first to demonstrate significantly increased androgen sensitivity in experimental hepatic carcinogenesis analogous to increased androgen receptor expression in human hepatocellular carcinoma. It may provide insight into steroid hormone sensitivity in developing tumors, and a means of testing potential therapeutic use of hormonal manipulation in human liver cancer.

Animals↗

Synovial chondromatosis of the temporomandibular joint: a light and electron microscopic study.

The light and electron microscopic features of synovial chondromatosis of the temporomandibular joint of one patient are presented. The affected synovial membrane and the cartilaginous nodules, which were freely movable in the joint space as well as attached to or incorporated in the synovial membrane, were examined. Light microscopic observation revealed metaplastic formation of these nodules within the subintima of the synovial membrane. Different stages of development of the nodules were observable. Electron microscopic examination of the cartilaginous nodules revealed features of mature chondrocytes well endowed with rough-surfaced endoplasmic reticulum and Golgi apparatus. The synovial intimal cells had a differentiated ultrastructural appearance. Several cytoplasmic organelles of the chondrocytes and intimal cells are described. The results of this study support the benign nature of synovial chondromatosis.

Cartilage↗

Physiological implications of trehalase from Phaseolus vulgaris root nodules: partial purification and characterization.

The purification and characterization of trehalase from common bean nodules as well as the role of this enzyme on growth, nodulation nitrogen fixation by examining the effects of the trehalase inhibitor validamycin A, was studied. Validamycin A did not affect plant and nodule mass, neither root trehalase and nitrogenase activity; however this treatment applied at the time of sowing increased nodule number about 16% and decreased nodule trehalase activity (16-fold) and the size of nodules. These results suggest that nodule trehalase activity of Phaseolus vulgaris could be involved in nodule formation and development. In addition, acid trehalase (EC 3.2.1.28) was purified from root nodules by fractionating ammonium sulfate, column chromatography on DEAE-sepharose and sephacryl S-300, and finally on native polyacrylamide gel electrophoresis. The purified homogeneous preparation of native acid trehalase exhibited a molecular mass of 42 and 45 kDa on SDS-PAGE. The enzyme has the optimum pH 3.9, Km of 0.109 mM, Vmax of 3630 nkat mg-1 protein and is relatively heat stable. Besides trehalose, it shows maximal activity with sucrose and maltose and, to a lesser degree melibiose, cellobiose and raffinose, and it does not hydrolyze on lactose and turanose. Acid trehalase was activated by Na+, Mn2+, Mg2+, Li+, Co2+, K+ and inhibited by Fe3+, Hg+ and EDTA.

Cations↗

Nodulation of Mimosa spp. by the beta-proteobacterium Ralstonia taiwanensis.

Several beta-proteobacteria have been isolated from legume root nodules and some of these are thought to be capable of nodulating and fixing N2. However, in no case has there been detailed studies confirming that they are the active symbionts. Here, Ralstonia taiwanensis LMG19424, which was originally isolated from Mimosa pudica nodules, was transformed to carry the green fluorescent protein (gfp) reporter gene before being used to inoculate axenically-grown seedlings of M. pudica and M. diplotricha. Plants were harvested at various intervals for 56 days after inoculation, then examined for evidence of infection and nodule formation. Nodulation of both Mimosa spp. was abundant, and acetylene reduction assays confirmed that nodules had nitrogenase activity. Confocal laser scanning microscopy (CLSM) showed that fresh M. pudica nodules with nitrogenase activity had infected cells containing bacteroids expressing gfp. In parallel, fixed and embedded nodules from both Mimosa spp. were sectioned for light and electron microscopy, followed by immunogold labeling with antibodies raised against gfp and nitrogenase Fe (nifH) protein. Significant immunolabeling with these antibodies confirmed that R. taiwanensis LMG19424 is an effective N2-fixing symbiont of Mimosa spp. Both species were infected via root hairs and, in all respects, the nodule ontogeny and development was similar to that described for other mimosoid legumes. The nodules were indeterminate with a persistent meristem, an invasion zone containing host cells being invaded via prominent infection threads, and an N2-fixing zone with infected cells containing membrane-bound symbiosomes.

Blotting, Western↗

Intralesional triamcinolone therapy for pretibial myxedema.

In a prospective study, nine patients with pretibial myxedema were treated with intralesional injections of triamcinolone acetonide. Complete resolution of the myxedematous plaques was obtained in seven of the nine patients. The other two patients failed to complete their treatment programs but did show partial resolution. For most patients the monthly injection of 8 ml or less of a solution containing 5 mg/ml of triamcinolone proved to be the most effective dosage schedule. No serious side effects were encountered. New nodules of myxedema developed in some patients after the initial completion of therapy; these nodules responded to reinjection using the same dosage schedule.

Adult↗

Leishmania braziliensis: development of primary and satellite lesions in the experimentally infected owl monkey, Aotus trivirgatus.

Twelve male and 8 female feral owl monkeys, Aotus trivirgatus, were inoculated intradermally at the dorsal base of the tail with 2 X 10(7) promastigotes (strains WR 128 or WR 539) or 5 X 10(5) amastigotes (strain WR 128) of Leishmania braziliensis panamensis, and the progression and regression of subsequent lesions were examined for up to 13 or 54 weeks after inoculation. Three of these monkeys had been infected previously with L. donovani, had been treated with meglumine antimoniate, and had recovered clinically from visceral leishmaniasis. All monkeys developed a cutaneous nodule at the inoculation site, but the size of the nodule varied (maximum 78 to 326 mm2 between 4 and 16 weeks after inoculation.) The initial nodule became ulcerated after 4 to 8 weeks in 17 of the 20 monkeys, and the ulcers persisted for 4 to 16 weeks until covered by a crust. Primary lesions disappeared by 17 to 52 weeks after inoculation, but satellite lesions, of similar morphology to the primary lesions but smaller, developed after 4 to 21 weeks in 14 of the monkeys. The primary nodule was excised in 4 monkeys at 6 weeks and did not recur nor did satellite lesions subsequently develop. The satellite lesions (median total number of 4, range 1 to 25) were adjacent to or at a maximum distance of 6 cm from the primary lesion, varied in size from 3 to 117 mm2, and persisted for 10 to 37 weeks. At 6 and 8 weeks after inoculation, tissue from the cutaneous leishmanial lesions from five monkeys was excised and examined. The granulomatous leishmanial lesions, located primarily in the dermis and subcutis, consisted of macrophages containing parasites, lymphocytes, plasma cells, and occasionally eosinophils. Satellite lesions at 14 weeks after inoculation were similar grossly and microscopically to the initial nodule. No significant differences were observed between promastigote or amastigote derived infections, between the two strains of L. b. panamensis, or between the course of infection based on the sex, age, karyotype, or country of origin of the owl monkeys. Cutaneous lesions developed when 5 X 10(5) amastigotes of L. b. panamensis (strain WR 128) were inoculated intradermally into the dorsal base of the tail, the upper eyelid, and the thorax of three monkeys. Leishmanial nodules which developed on the thorax regressed rapidly (after 2 to 5 weeks) whereas those on the upper eyelid and at the dorsal base of the tail persisted for 5 to 45 weeks after inoculation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Alfalfa Controls Nodulation during the Onset of Rhizobium-induced Cortical Cell Division.

The formation of first nodules inhibits subsequent nodulation in younger regions of alfalfa (Medicago sativa L.) roots by a feedback regulatory mechanism that controls nodule number systemically (G Caetano-Anollés, WD Bauer [1988] Planta 175: 546-557). Following inoculation with wild-type Rhizobium meliloti, almost all infections associated with cortical cell division developed into mature nodules. While the distribution of Rhizobium- induced cell divisions closely paralleled the distribution of first emergent nodules, only 9 to 15% of total cell division foci failed to become functional nodules. Nodule formation was restricted to the primary root when plants were inoculated before lateral root emergence. Excision of these primary root nodules allowed nodules to reappear in lateral roots clustered around the location of the root tip at the time of nodule removal. Apparently, this region regained susceptibility to infection within the first hours after excision of primary nodules and suppression of nodulation was restored a day later probably due to the development of new infection foci. Our results suggest that alfalfa controls nodulation during the onset of cell division in the root cortex and not during infection development as in soybean.

Journal Article↗

Therapeutic and persistent efficacy of doramectin against Dermatobia hominis in cattle.

One therapeutic and one persistent efficacy study were conducted in Brazil to evaluate doramectin at a dose rate of 200 micrograms/kg-1 against induced infestations of the tropical warble-fly, Dermatobia hominis. Doramectin was very effective in both the treatment of established infestations and also in the prevention of damage caused by the parasite. In the therapeutic trial, 12 calves were infested along the dorsal line with 25 first instar larvae of recent field isolates of D. hominis but in one calf nodules did not develop. Twenty-four days later animals were allocated to two groups on the basis of the number of parasite nodules present. Six calves were treated with doramectin, and five received saline solution. Animals were examined daily for 11 days post-treatment and the number of nodules mapped and recorded. Larvae that completed development were collected and incubated to evaluate viability. In the persistent efficacy study, 24 calves were allocated to six groups (T1-T6) of four animals each. On the day of treatment, three groups (T1, T3 and T5) were treated with saline and three groups (T2, T4 and T6) with doramectin. At 21 days, 28 days and 35 days post-treatment, 25 first instar D. hominis larvae were seeded along the dorsal line of each calf of T1 and T2, T3 and T4, and T5 and T6, respectively. Animals were examined daily for 18 days and the number of nodules mapped and recorded 6, 12 and 18 days post-infestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗