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PubMed1993

Genes for a microaerobically induced oxidase complex in Bradyrhizobium japonicum are essential for a nitrogen-fixing endosymbiosis.

We report the discovery of a Bradyrhizobium japonicum gene cluster (fixNOQP) in which mutations resulted in defective soybean root-nodule bacteroid development and symbiotic nitrogen fixation. The predicted, DNA-derived protein sequences suggested that FixN is a heme b and copper-binding oxidase subunit, FixO a monoheme cytochrome c, FixQ a polypeptide of 54 amino acids, and FixP a diheme cytochrome c and that they are all membrane-bound. The isolation and analysis of membrane proteins from B. japonicum wild-type and mutant cells revealed two c-type cytochromes of 28 and 32 kDa as the likely products of the fixO and fixP genes and showed that both were synthesized only under oxygen-limited growth conditions. Furthermore, fixN insertion and fixNO deletion mutants grown microaerobically or anaerobically (with nitrate) exhibited a strong decrease in whole-cell oxidase activity as compared with the wild type. The data suggest that the fixNOQP gene products are induced at low oxygen concentrations and constitute a member of the bacterial heme/copper cytochrome oxidase superfamily. The described features are compatible with the postulate that this oxidase complex is specifically required to support bacterial respiration in endosymbiosis.

Aerobiosis↗
PubMed1999

In vivo suppressor mutations correct a murine model of hereditary tyrosinemia type I.

Hereditary tyrosinemia type I and alkaptonuria are disorders of tyrosine catabolism caused by deficiency of fumarylacetoacetate hydrolase (FAH) and homogentisic acid dioxygenase (HGD), respectively. Tyrosinemia is a severe childhood disease that affects the liver and kidneys, but alkaptonuria is a more benign adult disorder in comparison. Because HGD is upstream of FAH in the tyrosine pathway, mice doubly mutant in both enzymes were found to be protected from the liver and renal damage of tyrosinemia as hypothesized. Mice mutant at the tyrosinemic locus but heterozygous for alkaptonuria spontaneously developed clonal nodules of functionally normal hepatocytes that were able to rescue the livers of some mice with this genotype. This phenotypic rescue was a result of an inactivating mutation of the wild-type homogentisic acid dioxygenase gene, thus presenting an example of an in vivo suppressor mutation in a mammalian model.

Acetoacetates↗
PubMed2002

Avian retrovirus infection causes naturally occurring glioma: isolation and transmission of a virus from so-called fowl glioma.

So-called fowl glioma is characterized by multiple nodular gliomatous growths associated with disseminated non-suppurative encephalitis. To investigate the possibility of the induction of the gliomatous lesions, chicks of Japanese bantams (Gallus gallus domesticus) and specific pathogen free chickens (C/O strain White Leghorn) were intracerebrally inoculated with a brain homogenate or culture supernatant from a bantam affected with fowl glioma. All bantams and 16 chickens (89%) in the inoculated groups showed non-suppurative encephalitis, and the 18 bantams (82%) and five chickens (28%) developed multiple nodules consisting of aggregations of astrocytes in the cerebrum. These astrocytes had avian leukosis virus (ALV) antigen. By Southern blot analysis, the ALV sequence was detected both in DNA prepared from the brains of the inoculated birds and in DNA from the inoculum. Ultrastructurally, tadpole-shaped particles, approximately 100 nm in diameter, were detected in the concentrated supernatant of the chicken embryo fibroblasts, and budding of the particles was noted. These results substantiated that fowl glioma of the bantams could be transmitted by intracerebral inoculation of the affected tissue and that the causal agent was an unidentified strain of ALV.

Animals↗
PubMed1973

Somite chondrogenesis. A structural analysis.

Light and electron microscopy are used in this study to compare chondrogenesis in cultured somites with vertebral chondrogenesis These studies have also characterized some of the effects of inducer tissues (notochord and spinal cord), and different nutrient media, on chondrogenesis in cultured somites Somites from stage 17 (54-60 h) chick embryos were cultured, with or without inducer tissues, and were fed nutrient medium containing either horse serum (HS) and embryo extract (EE), or fetal calf serum (FCS) and F12X Amino acid analyses were also utilized to determine the collagen content of vertebral body cartilage in which the fibrils are homogeneously thin (ca. 150 A) and unbanded. These analyses provide strong evidence that the thin unbanded fibrils in embryonic cartilage matrix are collagen. These thin unbanded collagen fibrils, and prominent 200-800 A protein polysaccharide granules, constitute the structured matrix components of both developing vertebral cartilage and the cartilage formed in cultured somites Similar matrix components accumulate around the inducer tissues notochord and spinal cord. These matrix components are structurally distinct from those in embryonic fibrous tissue The synthesis of matrix by the inducer tissues is associated with the inductive interaction of these tissues with somitic mesenchyme. Due to the deleterious effects of tissue isolation and culture procedures many cells die in somitic mesenchyme during the first 24 h in culture. In spite of this cell death, chondrogenic areas are recognized after 12 h in induced cultures, and through the first 2 days in all cultures there are larger accumulations of structured matrix than are present in equivalently aged somitic mesenchyme in vivo. Surviving chondrogenic areas develop into nodules of hyaline cartilage in all induced cultures, and in most non-induced cultures fed medium containing FCS and F12X There is more cell death, less matrix accumulation, and less cartilage formed in cultures fed medium containing HS and EE. The inducer tissues, as well as nutrient medium containing FCS and F12X, facilitate cell survival, the synthesis and accumulation of cartilage matrix, and the formation of cartilage nodules in cultured somites.

Amino Acids↗
PubMed1955

Studies on antibody production. III. The alum granuloma.

After subcutaneous injection of hen's ovalbumin or diphtheria toxoid precipitated with aluminum phosphate, the production of antibody, as judged by the presence in the tissues of antibody-containing cells, proceeds partly within the regional lymphatic glands and partly in the granulation tissue surrounding the nodule which develops at the site of injection. The first production of antibody takes place in the regional lymphatic gland and antibody production in the local granuloma becomes apparent only from 14 days onwards (rabbit). Antibody-containing plasma cells were demonstrated in the local granuloma up to 7 weeks. Antibody-containing cells in the regional lymphatic glands reach maximum numbers at 2 weeks following injection and decrease thereafter to few cells at 5 weeks. The adjuvant effect of the aluminum phosphate is interpreted as due partly to the delay in absorption of antigen from the local site of its injection which results in prolongation of stimulation of cells within the regional lymphatic glands, and partly to the production of a local granuloma which contains antibody-producing plasma cells.

Adjuvants, Immunologic↗
PubMed1983

Disseminated infection by Aspergillus terreus.

A patient with acute nonlymphocytic leukemia who received chemotherapy developed lung nodules and later central nervous system symptoms consistent with disseminated aspergillosis. The diagnosis was made at open lung biopsy by culturing the organism and observing in tissue sections conidia borne laterally along the hyphae, a characteristic of the Aspergillus terreus-flavipes group. This is the first reported case of disseminated A. terreus infection in an immunocompromised host.

Acute Disease↗
PubMed1992

Search for Ha-ras codon 61 mutations in liver tumours caused by hexachlorobenzene and Aroclor 1254 in C57BL/10ScSn mice with iron overload.

C57BL/10ScSn mice administered iron--dextran and fed the environmental pollutants hexachlorobenzene (HCB) and polychlorinated biphenyls (PCBs) develop hepatic nodules and carcinomas within 18 months. A range of lesions from the livers were analysed for the presence of mutations in the Ha-ras proto-oncogene at codon 61 using the polymerase chain reaction to amplify DNA from formalin-fixed sections, followed by oligonucleotide hybridization. Only two mutations from 23 preneoplastic and neoplastic lesions induced by HCB were detected (a focus of altered cells and a trabecular cell carcinoma). With Aroclor 1254 no mutations were detected in 28 areas at various stages of carcinogenesis analysed. Sequencing of the two mutations generated by HCB showed a C-->T transversion at the first base of codon 61 (carcinoma) and an A-->T transversion at the second base (proliferative focus). Thus, in marked contrast to some other systems of mouse liver tumour induction, hepatocarcinogenesis caused by HCB and PCBs in C57BL/10ScSn mice is an example of carcinogenesis which does not involve a high frequency of Ha-ras gene mutation at codon 61.

Animals↗
PubMed1986

Loa loa infection in temporary residents of endemic regions: recognition of a hyperresponsive syndrome with characteristic clinical manifestations.

Loiasis in residents of endemic areas is generally manifested by microfilaremia, episodic angioedema, periocular migration of adult worms, modest eosinophilia, and variable antibody levels. In 20 temporary residents who acquired loiasis in West Africa, however, the clinical presentations were markedly different. Only three of the 20 had detectable microfilaremia. Furthermore, these patients often showed a state of marked immunological hyperresponsiveness manifested by very high titers of antibody to filariae, increased levels of serum IgE, and profound hypereosinophilia--to levels greater than 3,000/mm3 in 18 of the 20. These patients were also notable for the increased severity, frequency, and pruritic nature of their angioedema. Also, significant complications occurred in seven of the 20; one patient developed endomyocardial fibrosis and six, renal disease after treatment with diethylcarbamazine. Thirteen of the 20 developed subcutaneous nodules; adult parasites were recovered from three of five of these patients who underwent biopsy. All of the patients responded to therapy with diminution of their clinical symptoms and decreases in levels of eosinophils, IgE, and antibody to filariae.

Adult↗
PubMed1986

Disseminated lobular capillary hemangioma (pyogenic granuloma). A clinicopathologic study of two cases.

The eruption of multiple lobular capillary hemangiomas (granulomata pyogenicum) is a previously documented but uncommon phenomenon. Reported cases have featured the recurrence of multiple satellite lesions after surgical removal of, or trauma to, a solitary capillary hemangioma. Sporadic cases of multifocal lesions arising de novo in both previously traumatized and uninjured skin have been described as well. We describe herein two unusual patients with disseminated lobular capillary hemangioma. One patient developed skin nodules in several sites, including the mouth, knee, thumb, and foot, after surgical removal of a solitary oculocutaneous neoplasm. The second patient had more than 700 skin lesions, distributed over the entire body. Unlike those in most previously reported examples of this condition, these two patients were elderly. Both were misdiagnosed clinically as having malignant vascular neoplasms, but the behavior of the lesions was benign, despite conservative surgical excisions in one patient and relative lack of therapeutic intervention in the other.

Facial Neoplasms↗
PubMed1998

Atrophic and plaquelike dermatofibrosarcoma protuberans.

It is clinically important to realize that dermatofibrosarcoma protuberans (DFSP) often begins as a nonprotuberant plaque and occasionally persists as such. Cases of what has been called atrophic DFSP have recently been reported. None of these cases varied either histologically or prognostically from classical nodular DFSP, and all should be considered part of the clinical spectrum of DFSP. However, histologic variants of DFSP can portend a worse prognosis. The fibrosarcomatous variant, which is fascicular and does not immunostain with anti-CD34, is an example. Recently, another fascicular variant that does positively immunostain with anti-CD34 has been described as plaquelike DFSP. We described a case of a DFSP that had histologically banal, slender fascicles of anti-CD34 immunostaining spindle cells in a clinically nonprotuberant plaque despite subsequently developing a nodule with typical storiform histology. The importance of anti-CD34 immunoperoxidase staining in the diagnosis and prognosis of DFSP variants is emphasized.

Antigens, CD34↗
PubMed2002

Rhabdomyosarcoma arising in a congenital melanocytic nevus.

A variety of malignancies have been reported to arise within congenital melanocytic nevi, most commonly malignant melanoma, but rarely rhabdomyosarcoma, liposarcoma, and malignant peripheral nerve sheath tumor as well. There have been only three documented cases of rhabdomyosarcoma arising within congenital melanocytic nevi: two embryonal rhabdomyosarcomas and one mixed liposarcoma and rhabdomyosarcoma. One of these cases was also associated with neurocutaneous melanosis. We report a fourth case of rhabdomyosarcoma originating from a congenital melanocytic nevus. A 4-year-old girl presented with a large ulcerated nodule that developed within a hairy congenital nevus on her left gluteal and sacral regions. Her parents refused postoperative adjuvant therapy, and she died 13 months after surgical excision. Histologic sections showed a lesion with two distinct components. There was an expansile proliferation of pleomorphic cells within a fibromyxoid stroma. The neoplastic cells were spindled, and some had abundant eosinophilic globular cytoplasm with occasional cross-striations characteristic of rhabdomyoblasts. They strongly expressed desmin and myoglobin and were negative for S-100 protein and HMB-45. The tumor merged with an adjacent congenital melanocytic nevus characterized by a proliferation of uniform nonatypical melanocytes. The finding of both rhabdomyoblastic and melanocytic differentiation within the same lesion lends support to the hypothesis of their derivation from common pluripotential stem cells or neural crest cells.

Biomarkers, Tumor↗
PubMed1984

Postoperative spindle cell nodules of genitourinary tract resembling sarcomas. A report of eight cases.

Eight cases of proliferative spindle cell nodules that developed 5 weeks to 3 months after operations on the lower genital tract of four women, and the lower urinary tract of four men, are described. The lesions ranged up to 4 cm in diameter, resembled spindle cell sarcomas on microscopical examination, and were initially interpreted as such in most of the cases. Six of the lesions were treated by local excision alone, and two by a radical surgical procedure, followed by radiation therapy in one case. The six patients whose lesions were treated inadequately on the assumption that they were sarcomas were free of disease 9-60 months (average, 28 months) postoperatively, and the two men who were treated by radical procedures were well 18 and 60 months later. The microscopic features, the unusual clinical setting, and the favorable prognosis of these lesions suggest that they were examples of a hitherto undescribed form of benign reactive lesion resembling a sarcoma.

Adult↗
PubMed1986

Necrobiotic xanthogranuloma with paraproteinemia. A review of 22 cases.

Cutaneous biopsy specimens from 22 patients showed the distinctive histopathologic pattern of necrobiotic xanthogranuloma within the dermis or subcutaneous tissue (or both). Twenty of the 22 patients had 1 or more serum protein abnormalities, consisting of an IgG monoclonal protein in 16, multiple myeloma in 3, cryoglobulinemia in 3, and an abnormal serum protein electrophoresis in 1. Cutaneous lesions were seen as discrete, slowly developing red nodules and plaques with a xanthomatized hue and a predilection for the face (periorbital region in particular), trunk, and extremities. Ulceration was a notable finding in 10 patients. Histologically, the dermis and lobules of subcutaneous tissue were involved with a granulomatous infiltrate containing bands of hyaline necrobiosis and bizarre foreign body, as well as Touton giant cells. Cholesterol clefts, lymphoid nodules with or without germinal centers, and foci of plasma cells were variable but significant features. Leukocyte monoclonal antibody studies in 6 patients demonstrated helper T cells within the granulomas. Electron microscopy in 3 cases showed lipid vacuoles in macrophages in the dermis and dendritic cells in the epidermis, and study confirmed this entity as a non-X histiocytosis. Pertinent laboratory findings, in addition to the serum protein abnormalities, included elevation of the erythrocyte sedimentation rate, leukopenia with absolute neutropenia, and decreased serum complement levels, as well as decreased levels of C1-esterase inhibitor in some patients. Thirteen of the 22 patients have survived, the mean duration being 9.5 years after the onset of cutaneous disease. While given to only a few patients in the current series, low-dose chemotherapy seems to induce a favorable response in both the cutaneous and the hematologic disease.

Adult↗
PubMed2001

Solitary pulmonary nodules: new wine in old bottles.

Management strategies for solitary pulmonary nodules have evolved slowly during the last 50 years. The goal has always been to facilitate the resection of malignant nodules without undue delay and to avoid exploratory thoracotomy for benign nodules. In the past decade, the development of reliable nodule enhancement techniques has replaced or become incorporated within some of the older strategies. In addition, some of the well-accepted concepts of the past have been undergoing critical reviews and reevaluations. These concepts include retrospective study of nodule diameters to recognize 2-year stability, the use of a watch-and-wait strategy using standard chest radiographs for prospective determination of stability, detection and recognition of calcification patterns on standard chest radiographs, and computed tomography for mediastinal staging.

Humans↗
PubMed2006

Biological tolerance of different materials in bulk and nanoparticulate form in a rat model: sarcoma development by nanoparticles.

In order to study the pathobiological impact of the nanometre-scale of materials, we evaluated the effects of five different materials as nanoparticulate biomaterials in comparison with bulk samples in contact with living tissues. Five groups out of 10 rats were implanted bilaterally for up to 12 months with materials of the same type, namely TiO2, SiO2, Ni, Co and polyvinyl chloride (PVC), subcutaneously with bulk material on one side of the vertebral column and intramuscularly with nanoparticulate material on the contralateral side. At the end of each implantation time, the site was macroscopically examined, followed by histological processing according to standard techniques. Malignant mesenchymal tumours (pleomorphic sarcomas) were obtained in five out of six cases of implanted Co nanoparticle sites, while a preneoplastic lesion was observed in an animal implanted with Co in bulk form. In the Ni group, all animals rapidly developed visible nodules at the implanted sites between 4 and 6 months, which were diagnosed as rhabdomyosarcomas. Since the ratio of surface area to volume did not show significant differences between the Ni/Co group and the TiO2/SiO2/PVC group, we suggested that the induction of neoplasia was not mediated by physical effects, but was mediated by the well-known carcinogenic impact of Ni and Co. The data from the Co group show that the physical properties (particulate versus bulk form) could have a significant influence on the acceleration of the neoplastic process.

Animals↗
PubMed1995

Lymphomatoid papulosis followed by Ki-1 positive anaplastic large cell lymphoma: proliferation of a common T-cell clone.

We report a case of lymphomatoid papulosis (LyP) followed by Ki-1 positive anaplastic large cell lymphoma (LCL). A 33-year-old man developed subcutaneous nodules in the left inguinal region and the left thigh after a seven-year-history of self-healing papulonecrotic lesions of LyP. Histological and immunohistochemical examination of the subcutaneous nodules revealed LCL. DNA was isolated from a nodule of the initial stage of LyP in 1988, a subcutaneous nodule of LCL in 1993, and a papule of LyP in 1993 which appeared after chemotherapy for LCL. T cell receptor gene rearrangement analysis demonstrated an identical rearranged pattern in all the three specimens, indicating that a common T cell clone proliferated throughout the course in both the LyP and LCL lesions.

Adult↗
PubMed2002

A case of hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber's disease) with dystrophic calcinosis cutis and retinal lesions.

A 65-year-old Japanese female developed a nodule on the distal interphalangealjoint of her right thumb. She also had multiple telangiectasias on her face, oral mucosa, tongue, nasal mucosa and upper extremities. A lip biopsy showed irregularly dilated capillaries and venules lined by flat endothelial cells. The nodule in the right thumb was resected. Histopathology revealed calcium deposits in the dermis. This case was diagnosed as dystrophic calcinosis cutis within hereditary hemorrhagic telangiectasia. Ophthalmologic examination showed bilateral retinal vascular lesions with dilated and tortuous retinal venules.

Aged↗
PubMed2005

Multiple cutaneous fibrous histiocytomas in association with systemic lupus erythematosus.

Cutaneous fibrous histiocytomas are usually regarded as superficial lesions and commonly known as dermatofibromas; however, unusual cases histologically showing fibrohistiocytic proliferation extending into the deeper dermis or subcutaneous tissues are occasionally experienced. Some authors propose this type as benign fibrous histiocytoma of the skin, distinct from dermatofibroma. We describe herein a case of systemic lupus erythematosus (SLE) who developed multiple nodules on the face, trunk and extremities. The nodule on the forehead did not present a typical clinical appearance of dermatofibroma, and histopathological examination showed fibrohistiocytic proliferation with a storiform pattern extending into the deep dermis and subcutaneous tissues. By contrast, histology of the nodule on the abdomen showed fibrohistiocytic proliferation confined to the dermis and compatible with dermatofibroma. Although multiple dermatofibromas are occasionally seen in patients with SLE, benign fibrous histiocytoma of the skin showing deeper invasion than dermatofibroma is rarely associated with SLE.

Adult↗