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Fine needle aspiration biopsy of primary mucinous carcinoma of the skin: a case report.

BACKGROUND: Primary mucinous carcinoma of the skin is a rare neoplasm of sweat gland origin. To date there are only 2 case reports in English describing its features on fine needle aspiration biopsy (FNAB). We describe an additional case and review the literature regarding this entity. To the best of our knowledge, this is the first reported case with a sentinel lymph node biopsy. CASE: A 78-year-old woman presented with a 3-cm left scalp mass at an outside institution. Following incomplete excision, multiple subcentimeter nodules developed in the skin adjacent to the biopsy site. FNAB of the nodules confirmed a recurrence of mucinous carcinoma. Clinical examination and extensive radiographic studies did not reveal primary disease elsewhere, thus supporting a diagnosis of primary mucinous carcinoma of the skin. At the time of wide excision of the residual tumor, sentinel lymph node biopsy revealed a single focus of micrometastasis. The patient declined adjuvant therapy and was disease free 6 months after the initial diagnosis. CONCLUSION: Cutaneous mucinous carcinoma is a tumor characterized by bland histocytologic features and abundant extracellular pools of mucin. Without a high index of suspicion, this rare entity may be overlooked or misdiagnosed. Numerous benign and malignant mucin-producing primary and secondary mimics exist, and immunohistochemistry offers limited benefits in differentiating them. Cytologic diagnosis of primary mucinous carcinoma of the skin is possible; however, correlation of clinical, radiologic and pathologic features is necessary to arrive at an accurate diagnosis.

Adenocarcinoma, Mucinous↗

[CT findings of hypersensitivity pneumonitis].

CT findings of 22 cases of hypersensitivity pneumonitis (HP) were evaluated on 1 cm slices. All cases were diagnosed by transbronchial lung biopsy and clinical information. The study population included 8 men and 14 women with a mean age of 43 years. The causative antigens were considered to be so-called summer type in 17 cases, air humidifier in 1, pigeon in 1 and paint spray (isocyanate was suspected) in 3. CT examination were performed at a mean of 1.5 weeks after admission. In conclusion, characteristic CT findings of HP include combination of small nodular shadows and slight elevation of lung density. The size of nodular shadows was usually within 1 cm diameter, and their distribution was considered to be a centrilobular pattern, representing alveolitis and granuloma formation in a secondary lobule. It was though that the slight elevation of lung density developed when the disease extended all over the secondary lobule and the nodules developed when the disease was limited to the centrilobular lesion. In most cases, significant changes in proximal bronchi and pulmonary vasculatures could not be detected. The presence of segmental or lobar distribution of the shadows was also suggested. In addition to the typical findings, various other findings were also revealed; irregular shaped dense shadows, subpleural curvilinear shadow and honeycombing formation, especially in chronic cases. These findings have caused some difficulty in distinguishing HP from other interstitial diseases. More precise information can probably be obtained by thin slice CT than by 1 cm slice thicknesses, nevertheless, the standard method of CT should yield a useful diagnostic imaging.

Adult↗

The soybean NRAMP homologue, GmDMT1, is a symbiotic divalent metal transporter capable of ferrous iron transport.

Iron is an important nutrient in N2-fixing legume root nodules. Iron supplied to the nodule is used by the plant for the synthesis of leghemoglobin, while in the bacteroid fraction, it is used as an essential cofactor for the bacterial N2-fixing enzyme, nitrogenase, and iron-containing proteins of the electron transport chain. The supply of iron to the bacteroids requires initial transport across the plant-derived peribacteroid membrane, which physically separates bacteroids from the infected plant cell cytosol. In this study, we have identified Glycine max divalent metal transporter 1 (GmDmt1), a soybean homologue of the NRAMP/Dmt1 family of divalent metal ion transporters. GmDmt1 shows enhanced expression in soybean root nodules and is most highly expressed at the onset of nitrogen fixation in developing nodules. Antibodies raised against a partial fragment of GmDmt1 confirmed its presence on the peribacteroid membrane (PBM) of soybean root nodules. GmDmt1 was able to both rescue growth and enhance 55Fe(II) uptake in the ferrous iron transport deficient yeast strain (fet3fet4). The results indicate that GmDmt1 is a nodule-enhanced transporter capable of ferrous iron transport across the PBM of soybean root nodules. Its role in nodule iron homeostasis to support bacterial nitrogen fixation is discussed.

Amino Acid Sequence↗

Progression of chronic hepatitis and preneoplasia in Helicobacter hepaticus-infected A/JCr mice.

Helicobacter hepaticus infection induces sustained inflammation and carcinoma of the liver in A/JCr mice, and serves as a model of human cancers associated with viral hepatitis and H. pylorichronic gastritis. Here we describe the pathogenesis of premalignant disease in A/JCr mice infected with H. hepaticus. We inoculated dams intragestationally and/or pups postnatally, and evaluated offspring at 3, 6, or 12 months. Mice infected at or before 3 weeks of age, but not at 12 weeks, developed disease. Male mice were most affected, but expressed a bimodal pattern of susceptibility. Males exhibited lobular necrogranulomatous and interface (chronic active) hepatitis, while females usually developed intraportal (chronic persistent) hepatitis. Portal inflammation was slowly progressive, with tertiary lymphoid nodule development by 12 months. Hepatic bacterial load and preneoplastic lesions, including clear and tigroid cell foci of cellular alteration, were correlated with lobular hepatitis severity. No extrahepatic surrogate disease marker reliably predicted individual hepatitis grade. In conclusion, gender and bacterial exposure timing are key determinants of H. hepaticus disease outcomes. Intrahepatic inflammation is driven by local signals characterized by a vigorous but nonsterilizing immune response. Continued study of chronic hepatitis progression may reveal therapeutic targets to reduce the risk of hepatocellular carcinoma.

Alanine Transaminase↗

Differential expression within the glutamine synthetase gene family of the model legume Medicago truncatula.

The glutamine synthetase (GS) gene family of Medicago truncatula Gaertn. contains three genes related to cytosolic GS (MtGSa, MtGSb, and MtGSc), although one of these (MtGSc) appears not to be expressed. Sequence analysis suggests that the genes are more highly conserved interspecifically rather than intraspecifically: MtGSa and MtGSb are more similar to their homologs in Medicago sativa and Pisum sativum than to each other. Studies in which gene-specific probes are used show that both MtGSa and MtGSb are induced during symbiotic root nodule development, although not coordinately. MtGSa is the most highly expressed GS gene in nodules but is also expressed to lower extents in a variety of other organs. MtGSb shows higher levels of expression in roots and the photosynthetic cotyledons of seedlings than in nodules or other organs. In roots, both genes are expressed in the absence of an exogenous nitrogen source. However the addition of nitrate leads to a short-term, 2- to 3-fold increase in the abundance of both mRNAs, and the addition of ammonium leads to a 2-fold increase in MtGSb mRNA. The nitrogen supply, therefore, influences the expression of the two genes in roots, but it is clearly not the major effector of their expression. In the discussion section, the expression of the GS gene family of the model legume M. truncatula is compared to those of other leguminous plants.

Ammonia↗

Nodule initiation involves the creation of a new symplasmic field in specific root cells of medicago species.

The organogenesis of nitrogen-fixing nodules in legume plants is initiated in specific root cortical cells and regulated by long-distance signaling and carbon allocation. Here, we explore cell-to-cell communication processes that occur during nodule initiation in Medicago species and their functional relevance using a combination of fluorescent tracers, electron microscopy, and transgenic plants. Nodule initiation induced symplasmic continuity between the phloem and nodule initials. Macromolecules such as green fluorescent protein could traffic across short or long distances from the phloem into these primordial cells. The created symplasmic field was regulated throughout nodule development. Furthermore, Medicago truncatula transgenic plants expressing a viral movement protein showed increased nodulation. Hence, the establishment of this symplasmic field may be a critical element for the control of nodule organogenesis.

Biological Transport↗

A case of lymphocutaneous nocardiosis with a review of lymphocutaneous nocardiosis reported in Japan.

An 82-year-old Japanese male developed nodules and ulcers along the lymphatics after a fall in the garden of his house resulting in injuries to the dorsum of his left hand which lasted for 3 months. Nocardia brasiliensis was isolated from a nodule, supporting a diagnosis of the lymphocutaneous type of nocardiosis. He had previously developed generalized bone metastasis from prostatic cancer, and his resulting depressed immunity might have played a part in the nocardiosis genesis. Sixteen cases of the lymphocutaneous type of nocardiosis reported in Japan were reviewed.

Abscess↗

The products of Rhizobium genes, psi and pss, which affect exopolysaccharide production, are associated with the bacterial cell surface.

Translational fusions between a mutant phoA (lacking its promoter, ribosomal binding site and signal peptide sequence) and Rhizobium 'symbiotic' genes were isolated. Since these fusions expressed alkaline phosphatase (AP), the product of phoA, the genes into which phoA was inserted apparently specify proteins located in the bacterial periplasm or cell membrane, the compartment in which AP has activity. These genes were psiA and genes upstream of psiA (psiA is required for normal nodule development and strains with multicopy psiA fail to make exopolysaccharide (EPS) and to nodulate). Fusions between phoA and pss (exo) genes, which are required for EPS production, also resulted in the expression of AP indicating that products of these pss genes were located at the cell surface. Using gus fusions to psiA and pssA, we found that the former was expressed in N2-fixing bean root nodules but the latter was not.

Alkaline Phosphatase↗

Genetic locus required for antigenic maturation of Rhizobium etli CE3 lipopolysaccharide.

Rhizobium etli modifies lipopolysaccharide (LPS) structure in response to environmental signals, such as low pH and anthocyanins. These LPS modifications result in the loss of reactivity with certain monoclonal antibodies. The same antibodies fail to recognize previously isolated R. etli mutant strain CE367, even in the absence of such environmental cues. Chemical analysis of the LPS in strain CE367 demonstrated that it lacked the terminal sugar of the wild-type O antigen, 2,3,4-tri-O-methylfucose. A 3-kb stretch of DNA, designated as lpe3, restored wild-type antigenicity when transferred into CE367. From the sequence of this DNA, five open reading frames were postulated. Site-directed mutagenesis and complementation analysis suggested that the genes were organized in at least two transcriptional units, both of which were required for the production of LPS reactive with the diagnostic antibodies. Growth in anthocyanins or at low pH did not alter the specific expression of gusA from the transposon insertion of mutant CE367, nor did the presence of multiple copies of lpe3 situated behind a strong, constitutive promoter prevent epitope changes induced by these environmental cues. Mutations of the lpe genes did not prevent normal nodule development on Phaseolus vulgaris and had very little effect on the occupation of nodules in competition with the wild-type strain.

Carbohydrate Sequence↗

Adenovirus-mediated p53 tumor suppressor gene therapy against subcutaneous HuH7 hepatoma cell line nodule of nude mice.

Mutations of the tumor-suppressor gene p53 have been found in 30-50% cases of hepatocellular carcinoma (HCC). In this study, E1-negative adenoviral vector encoding wild-type p53 under the control of the human cytomegalovirus promoter (AdCMV-p53w) was constructed to evaluate its therapeutic efficacy against tumor nodules developing after injection of HuH7 cell lines in ten nude mice. When each nodule had reached 10 mm in perpendicular diameter, 1.5 x 10(8) pfu of AdCMV-p53w per session was injected intratumorally as follows: In group I (n=3), five sessions were injected every other day. In group II (n=3), only one session. Group III (n=4) as negative controls. The mice were sacrificed at 28 days post AdCMV-p53w injection. Tumor growth was significantly suppressed and delayed in group I and II compared to group III as compared by tumor volume at the end of observation. These results suggest that AdCMV-p53w may not only be effective in treating HCCs expressing mutant p53, but also useful as a local injectable gene therapy.

Adenoviruses, Human↗

Keratoacanthoma as a postoperative complication of skin cancer excision.

BACKGROUND: Keratoacanthomas usually occur spontaneously as a single rapidly growing tumor on sun-exposed skin. Multiple keratoacanthomas are rarely seen. Keratoacanthomas may also develop after trauma, laser resurfacing, radiation therapy, and at the donor site after skin grafting. OBJECTIVE: We report 6 cases of keratoacanthomas that developed in and around healing and healed surgical sites after treatment of skin cancer. These tumors developed 1 to 3 months after surgery and were sometimes multiple. METHODS: We performed follow-up examinations of patients' wounds after the treatment of skin cancer. Histological examination of nodules developing in the margins of healing wound sites and in the scars of healed wound sites after Mohs micrographic surgery revealed keratoacanthomas. RESULTS: The tumors presented as a rapidly growing nodule or nodules, with the typical morphology and pathology of keratoacanthoma. One patient developed multiple keratoacanthomas at surgical and nonsurgical sites. These nodules were treated by a combination of excision, curettage and electrodesiccation, and oral isotretinoin, 4 mg/d. CONCLUSION: Keratoacanthoma must be considered in the differential diagnosis of a rapidly growing nodule within or around the surgical site after skin cancer surgery.

Aged↗

Purification, cDNA Cloning, and Developmental Expression of the Nodule-Specific Uricase from Phaseolus vulgaris L.

Nodule-specific uricase (uricase II) from Phaseolus vulgaris L. was purified to homogeneity by chromatographic methods. Purification data indicated that uricase II is approximately 2% of the total soluble protein from mature nodules. Specific antiserum was raised and used to determine the developmental expression and for immunoselection of polysomes. Uricase II was antigenically detected early in nodule development, 2 to 3 days before nitrogen fixation. Uricase-encoding cDNA clones were isolated by hybridizing a nodule-specific pUC9 cDNA library with labeled mRNA from immunoselected polysomes and a 35,000 molecular weight uricase II-encoding cDNA from soybean. An homologous clone (pNF-UR07) was used to assess the expression pattern of the specific transcript during development. Northern-blot analysis indicated that uricase II mRNA is exclusively expressed in nodule tissue.

Journal Article↗

Severe abdominal involvement as the initial manifestation of cutaneous polyarteritis nodosa in a young girl.

We report a young girl who developed ingravescent intestinal symptoms as the first manifestation of cutaneous polyarteritis nodosa (PAN) while the typical skin nodules developed later during the disease course. Cutaneous PAN predominantly affects children and presents with crops of painful skin nodules in the medial aspect of the foot, often preceded by sore throat. Visceral manifestations including gut involvement are commonly associated with the classical form of PAN while they are rarely reported in the cutaneous form. In our patient the severity of the abdominal symptoms required a laparoscopy, which revealed diffuse erythematosus swelling of the intestine on the serosal side. The administration of penicillin and steroids was followed by a dramatic improvement in the disease course. Chronic anterior uveitis developed 4 months after the disease onset and responded to local treatment. At a 2-year follow-up the girl is in good condition under prophylaxis with benzathine-penicillin with no recurrence of the illness. Our case confirms that cutaneous PAN is often related to streptococcal infection, and suggests that ASO titers should be determined in children with vasculitides to ensure a timely diagnosis and treatment of the condition if present.

Abdominal Pain↗

Sequential histological and histochemical study of the rat liver during aflatoxin B1-induced carcinogenesis.

Male Wistar rats were given 50 mug of aflatoxin B1 twice a week for 4 weeks, and thereafter 75 mug twice a week for 10 weeks. Their livers were investigated histologically and histochemically for glycogen, RNA, fat, alkaline and acid phosphatases, adenosine triphosphatase, 5'-nucleotidase, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, succinic dehydrogenase, and alkaline and acid nucleases. No significant lesions occurred before 15 weeks. During this period, the liver was histochemically unchanged except for a periportal decrease of alkaline phosphatase and adenosine triphosphatase. Scattered hepatocytes with a strong glucose-6-phosphatase activity appeared. These changes represent toxic effects of aflatoxin B1 and are irrelevant to carcinogenesis. From 15 weeks onward, three types of liver cell hyperplastic foci and nodules developed. Histologically, and with respect to glycogen, fat, and RNA content, only two of these types were considered as potential precursors of hepatocarcinomas. However, all types exhibited a decrease or absence of the enzymes studied. Both histological and histochemical changes stressed the complex heterogeneity existing between and within hepatic foci and nodules. From 11 months on, hepatocarcinomas developed. The tumors disclosed similar histochemical changes. This similarity further supports the "precarcinomatous" nature of hyperplastic foci and nodules. It appears that focal changes in surface as well as in cytoplasmic and nuclear enzymes are intimately and very early linked to the carcinogenic process. Whether they are fundamental or only represent an epiphenomenon remains unclear.

Acid Phosphatase↗

No effect of RU 486 (mifepristone) on hepatocellular tumorigenesis in orchiectomized male mice induced by 3'-methyl-4-dimethylaminoazobenzene.

Effects of RU 486 (mifepristone) on hepatocellular tumorigenesis in orchiectomized male mice induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) were investigated. Male mice that had been treated with 3'-Me-DAB neonatally were orchiectomized at one month of age, and injected daily with vehicle only or RU 486 at 0.2 or 0.4 mg/day thereafter. In the liver of orchiectomized males injected with vehicle only, adenomatous nodules developed at incidences of 16.2 and 38.5% at 9 and 12 months of age, respectively, but no carcinomas developed at these ages. Injections of RU 486 at 0.2 or 0.4 mg/day neither affect incidences of adenomatous nodules in the liver, their numbers per mouse, and their areas, nor promote the development of carcinomas. The present results suggest that the long term administration of RU 486 has no effects on hepatocellular tumorigenesis.

Animals↗

Interleukin-1 alpha stimulates the release of prostaglandin E2 and phospholipase A2 from fetal rat calvarial cells in vitro: relationship to bone nodule formation.

We have shown previously that interleukin-1 (IL-1) has biphasic effects on the formation of bone nodules in long-term cultures of fetal rat calvarial (RC) cells (Ellies and Aubin, Cytokine 2:430-437, 1990). To determine the role of arachidonic acid metabolism in this process, we have examined the release of prostaglandin E2 (PGE2) and phospholipase A2 (PLA2) from RC cells under conditions that allowed concomitant analysis of the formation of bone nodules. Recombinant human IL-1 alpha (rhIL-1 alpha) stimulated PGE2 and PLA2 release in a time- and dose-dependent manner. PGE2 release was highest in preconfluent cultures (days 1-6) and was stimulated up to 8.5-fold in response to 50 U/ml of rhIL-1 alpha. In contrast, extracellular PLA2 activity was maximal in postconfluent cultures, with 50 U/ml of rhIL-1 alpha causing a 20-fold increase by day 15. PLA2 release by RC cells was not significantly affected by PGE2, the glucocorticoid dexamethasone, or the cyclooxygenase inhibitor indomethacin. Indomethacin partially blocked the inhibition of bone nodule formation caused by rhIL-1 alpha, and exogenous PGE2 reversed this effect. Addition of group I PLA2 from Naja naja venom to RC cells had no effect on bone nodule development; however, group II PLA2 from Crotalus adamanteus venom inhibited the formation of bone nodules in a dose range similar to that induced by rhIL-1 alpha. These results indicate that PGE2 release does not have a direct temporal correlation with increases in PLA2 activity. In addition, the data show that only part of the inhibition of bone formation seen with rhIL-1 alpha is mediated by PGE2 and suggest that extracellular PLA2 also accounts for part of the inhibition.

Animals↗

Rheumatoid nodules do not predict response to treatment with slow-acting anti-rheumatic drugs.

Rheumatoid nodules have been associated with a poor long-term prognosis. We investigated whether they predict a poor response to treatment with slow-acting anti-rheumatic drugs (SAARDs). Two hundred and twenty-eight patients with rheumatoid arthritis (RA) were treated for six months with a SAARD. Clinical and laboratory assessments of disease activity were made initially and after 6 months' treatment. Patients were divided into two groups according to the presence or absence of nodules at entry. Twenty-one % had nodules before treatment but their response was no different to patients without nodules (79%), both groups showing improvements in all variables. Males were more likely to develop nodules and had a relative risk of 1.7. High titres of rheumatoid factor correlated with nodules and no sero-negative patients had nodules. We conclude that nodules are not predictive of poor response to treatment with a SAARD, despite their presence being associated with a poor long-term prognosis. One possible implication is that SAARDs themselves, despite an early response, may not effect long-term outcome.

Anti-Inflammatory Agents↗

The Rhizobial hemA Gene Is Required for Symbiosis in Species with Deficient [delta]-Aminolevulinic Acid Uptake Activity.

Most rhizobial hemA mutants induce root nodules on their respective legume hosts that lack nitrogen fixation activity and leghemoglobin expression. However, a Bradyrhizobium japonicum hemA mutant elicits effective nodules on soybean, and we proposed previously that synthesis and uptake of the heme precursor [delta]-aminolevulinic acid (ALA) by the plant and bacterial symbiont, respectively, allow mutant rescue (I. Sangwan, M.R. O'Brian [1991] Science 251: 1220-1222). In the present work, the B. japonicum hemA mutant MLG1 elicited normal nodules on three hosts, including cowpea, a plant that is not effectively nodulated by a hemA mutant of Rhizobium sp. These data indicate that B. japonicum rather than soybean possesses the unique trait that allows normal nodule development by a hemA mutant. Cowpea expressed glutamate-dependent ALA formation activity in nodules induced by B. japonicum strains I110 or MLG1 and by Rhizobium sp. ANU240. Exogenous ALA was taken up by B. japonicum bacteroids isolated from soybean or cowpea nodules, and the kinetics of uptake were biphasic. By comparison, Rhizobium sp. ANU240 had very low ALA uptake activity. In addition, ALA uptake was observed in cultured cells of B. japonicum but not in cultured cells of three other rhizobial species tested. We suggest that the differential success of legume-rhizobial hemA symbioses is due to an ALA uptake activity in B. japonicum that is deficient in other rhizobia, thereby further validating the ALA rescue hypothesis.

Journal Article↗