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[A case of smoldering ATLL in high risk family and familial double infection of HTLV-1 and HBV].

A 35-year-old male from Kagoshima prefecture developed nodules with asymptomatic erythema on both upper eyelids, both hands and upper right leg in April 1986. On April 10, 1987, biopsy of skin lesions revealed numerous atypical CD4 positive lymphocytes which had invaded the dermis around the vessels. Analysis of serum showed positive antibody titer (X40) against the human T lymphotropic virus type I (HTLV-I) with some flower cells evident in peripheral blood; however, no infiltration into bone marrow or lymph nodes could be seen. Lymphocytes from peripheral blood and from the skin lesion of the right leg showed monoclonal integration of HTLV-I proviral DNA. Chronic active hepatitis B virus (HBV) was also a complicating factor. Familial study revealed all three family members to be infected with HTLV-1 as well as HBV. Proviral integration of HTLV-I was the intermediate type in two out of the three. From the results, a diagnosis of smoldering adult T cell leukemia-lymphoma (ATLL) was made in this patient with high risk to family members. Herein we discuss the development of ATLL in this case and infection among family members.

Adult↗

Transformation of mycosis fungoides: T-cell receptor beta gene analysis demonstrates a common clonal origin for plaque-type mycosis fungoides and CD30+ large-cell lymphoma.

It is well recognized that patients with classical mycosis fungoides (MF) may develop a large-cell lymphoma (LCL), a phenomenon known as "transformation." An unresolved issue regarding the transformation of MF is whether MF and LCL represent two separate lymphomas or whether they are derived from the same T-cell clone. We report the clinicopathologic, immunophenotypic, and immunogenotypic analysis of MF and LCL in a white male. He developed a rash at age 51 that was diagnosed at age 56 as clinical stage IA patch/plaque MF. After topical nitrogen mustard and total skin electron beam therapy for progressive generalized CD3+CD4+ patch/plaque lesions, he developed nodules of Ki-1+ (CD30+) T-LCL at age 72. Southern blot analysis of DNA digested with Bg/II or BamHI and probed with a T-cell receptor (TCR)-beta gene J beta 1/J beta 2 probe showed a single, identical rearranged band in both the MF and LCL skin lesions that had been obtained 4 years apart. V beta gene family--specific gene amplification assays demonstrated dominant V beta 6 PCR products in both types of lesions. These PCR products and lesional cDNA exhibited a monoclonal pattern when amplified with consensus TCR-beta gene VDJ joint primers and electrophoresed under conditions that allowed the resolution of small differences in size. Furthermore, sequence analysis of the V beta 6 PCR products amplified from both the MF and LCL lesions showed an identical nucleotide sequence involving V beta 6.4, D beta 1.1, J beta 1.2, and C beta 1. These findings indicate that both the MF and the LCL in this patient arose from the same T-cell clone and that these diseases developed at a stage in the clone's differentiation subsequent to rearrangement of the TCR-beta gene.

Aged↗

Estrogen receptor-alpha, bcl-2 and c-myc gene expression in fibroadenomas and adjacent normal breast: association with nodule size, hormonal and reproductive features.

Fibroadenomas are the most common benign lump in females. The study of gene alterations and/or deregulation in reproductive years may help explain hormonal physiological processes involved in nodule development and evolution. The objective was to compare ER-alpha, c-myc, and bcl-2 gene expression in breast fibroadenomas and in normal tissue and evaluate menstrual cycle, parity, and oral contraceptive influences. Fifty-seven premenopausal women (14-49 years) undergoing surgical removal of fibroadenomas were selected. Samples from fibroadenomas and circumjacent normal tissue were obtained for RT-PCR paired analysis. Patients were divided in groups according to menstrual cycle, use of contraceptives and parity. Tissue from 32 patients was adequate for RT-PCR. Paired analysis showed higher expression of ER-alpha (P=0.012) and bcl-2 (P=0.001) in fibroadenomas than in normal breast, while c-myc presented a similar expression (P=0.655). ER-alpha was higher in fibroadenomas of patients in follicular phase versus contraceptive users and normal tissue (P=0.003); bcl-2 was higher in fibroadenomas of patients in luteal phase than in the normal samples from all groups (P=0.007). c-myc did not differ according to menstrual cycle, but was higher in fibroadenomas>3 cm versus<3 cm (P=0.015) and in nulliparous women (P=0.04). A positive correlation between c-myc levels and fibroadenoma diameter was demonstrated (r=0.536; P=0.007). Nulliparous mean nodule diameter was superior than parous women (P=0.008). In conclusion, the expression of ER-alpha, bcl-2 and c-myc depends on hormonal and reproductive factors, with a possible contribution to lump formation and evolution.

Adolescent↗

[Extra-nodal Rosai-Dorfman disease: a case report with thyroid involvement].

Extra nodal involvement by Rosaï-Dorfman disease (RDD) is not rare but remains poorly described clinically and microscopically. We report a case of RDD involving the thyroid and revealed by a 15 mm cold nodule developed on an ancient goiter. The patient was a 53 year old North African woman. She also presented an involvement of cervical lymph nodes, respiratory tract and right kidney. Microscopic analysis of thyroid revealed a diffuse and dense infiltrate of large pale histiocytes with few features of lymphophagocytosis. To the best of our knowledge, this is the fifth case reported in the literature. In previous reported cases, thyroid RDD was associated to constant lymph node involvement (massive lymphadenopathy in 3 cases and occult in one case) and no other extra nodal localization except the respiratory tract in one case. The characteristic features of lymphophagocytosis must be searched with great care.

Female↗

Rhizobium meliloti mutants that overproduce the R. meliloti acidic calcofluor-binding exopolysaccharide.

The acidic Calcofluor-binding exopolysaccharide of Rhizobium meliloti Rm1021 plays one or more critical roles in nodule invasion and possibly in nodule development. Two loci, exoR and exoS, that affect the regulation of synthesis of this exopolysaccharide were identified by screening for derivatives of strain Rm1021 that formed mucoid colonies that fluoresced extremely brightly under UV light when grown on medium containing Calcofluor. The exopolysaccharide produced in large quantities by the exoR95::Tn5 and exoS96::Tn5 strains was indistinguishable from that produced by the parental strain Rm1021, and its synthesis required the function of at least the exoA, exoB, and exoF genes. Both the exoR and exoS loci were located on the chromosome, and the exo96::Tn5 mutation was 84% linked to the trp-33 mutation by phi M12 transduction. Synthesis of the Calcofluor-binding exopolysaccharide by strain Rm1021 was greatly stimulated by starvation for ammonia. In contrast, the exoR95::Tn5 mutant produced high levels of exopolysaccharide regardless of the presence or absence of ammonia in the medium. The exoS96::Tn5 mutant produced elevated amounts of exopolysaccharide in the presence of ammonia, but higher amounts were observed after starvation for ammonia. The presence of either mutation increased the level of expression of exoF::TnphoA and exoP::TnphoA fusions (TnphoA is Tn5 IS50L::phoA). Analyses of results obtained when alfalfa seedlings were inoculated with the exoR95::Tn5 strain indicated that the mutant strain could not invade nodules. However, pseudorevertants that retained the original exoR95::Tn5 mutation but acquired unlinked suppressors so that they produced an approximately normal amount of exopolysaccharide were able to invade nodules and fix nitrogens. The exoS95::Tn5 strain formed Fix+ nodules, although some minor variability was observed.

Benzenesulfonates↗

A Sinorhizobium meliloti lipopolysaccharide mutant altered in cell surface sulfation.

The Rhizobium-legume symbiosis involves the formation of a novel plant organ, the nodule, in which intracellular bacteria reduce molecular dinitrogen in exchange for plant photosynthates. Nodule development requires a bacterial signal referred to as Nod factor, which in Sinorhizobium meliloti is a beta-(1,4)-linked tetramer of N-acetylglucosamine containing N-acyl and O-acetyl modifications at the nonreducing end and a critical 6-O-sulfate at the reducing end. This sulfate modification requires the action of three gene products: nodH, which catalyzes the sulfonyl transfer, and nodPQ, which produce the activated form of sulfate, 3'-phosphoadenosine-5'-phosphosulfate. It was previously reported that S. meliloti cell surface polysaccharides are also covalently modified by sulfate in a reaction dependent on NodPQ. We have further characterized this unique form of bacterial carbohydrate modification. Our studies have determined that one of the nodPQ mutant strains used in the initial study of sulfation of cell surface harbored a second unlinked mutation. We cloned the gene affected by this mutation (referred to as lps-212) and found it to be an allele of lpsL, a gene previously predicted to encode a UDP-glucuronic acid epimerase. We demonstrated that lpsL encoded a UDP-glucuronic acid epimerase activity that was reduced in the lps-212 mutant. The lps-212 mutation resulted in an altered lipopolysaccharide structure that was reduced in sulfate modification in vitro and in vivo. Finally, we determined that the lps-212 mutation resulted in a reduced ability to elicit the formation of plant nodules and by altered infection thread structures that aborted prematurely.

Bacterial Proteins↗

Carbon and nitrogen limitations on soybean seedling development.

Carbon and nitrogen limitations on symbiotically grown soybean seedlings (Glycine max [L.] Merr.) were assessed by providing 0.0, 1.0, or 8.0 millimolar NH(4)NO(3) and 320 or 1,000 microliters CO(2)/liter for 22 days after planting. Maximum development of the Rhizobium-soybean symbiosis, as determined by acetylene reduction, was measured in the presence of 1.0 millimolar NH(4)NO(3) under both levels of CO(2). Raising NH(4)NO(3) from 0.0 to 8.0 millimolar under 320 microliters CO(2)/liter increased plant dry weight by 251% and Kjeldahl N content by 287% at 22 days after planting. Increasing NH(4)NO(3) from 1.0 to 8.0 millimolar under 320 microliters CO(2)/liter increased total dry weight and Kjeldahl N by 100 and 168%, respectively, on day 22. Raising CO(2) from 320 to 1,000 microliters CO(2)/liter during the same period had no significant effect on Kjeldahl N content of plants grown with 0.0 or 1.0 millimolar NH(4)NO(3). The maximum CO(2) treatment effects were observed in plants supplied with 8.0 millimolar NH(4)NO(3), where dry weight and Kjeldahl N content were increased 64% and 20%, respectively. An increase in shoot CO(2)-exchange rate associated with the CO(2)-enrichment treatment was reflected in a significant increase in leaf dry weight and starch content for plants grown with 1,000 microliters CO(2)/liter under all combined N treatments. These data show directly that seedling growth in symbiotically grown soybeans was limited primarily by N availability. The failure of the CO(2)-enrichment treatment to increase total plant N significantly in Rhizobium-dependent plants indicates that root nodule development and functioning in such plants was not limited by photosynthate production.

Journal Article↗

Clinical significance of low titer anti-nuclear antibodies in early rheumatoid arthritis: implications on the presentation and long-term course of the disease.

The objective of this study was to evaluate the clinical significance of anti-nuclear antibodies (ANA) detected in the early stages of rheumatoid arthritis (RA), by a retrospective comparison of the clinical, laboratory, and therapeutic characteristics of patients with or without ANA. The files of 99 longstanding seropositive RA patients were reviewed. Data relating to demographics, medical history, family history, physical findings, extra-articular complications, laboratory tests, drugs [dosage, duration. efficacy, combinations, adverse effects (AEs)], intra-articular injections, and surgery were recorded. Patients with or without ANA at presentation of their disease were compared using chi-square and t-tests. Fifty-two ANA positive (group 1) and 47 ANA negative (group 2) patients were enrolled in the study. All were comparable in terms of their mean age, age at diagnosis, follow-up duration (approximately 10.5 years), and male:female (M:F) ratio. On admission, pain complaints were more pronounced in group 1 (P = 0.004 in the feet), but the physical findings did not differ. Deformities and nodules developed in similar numbers. Extra-articular complications were evenly distributed; vasculitis, however, was significantly more prevalent in ANA positive (10/52) than in ANA negative (2/47) patients. Thyroid disease was more common in group 2 (10/47 vs 3/52). Laboratory tests (presentation and maximal values) were similar, with the exception of higher anti-DNA (but within normal ranges) and gamma-globulin% in group 1. Group 1 used more drugs prior to diagnosis. Corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs) were evenly used. Combination therapy, joint injections, and surgery were more prevalent in group 2. AEs to various DMARDs were more common in group 1. Although similar in many aspects, RA patients with ANA tend to present with more pain complaints, a higher risk of vasculitis and AEs relating to use of DMARDs, while those without ANA needed more aggressive therapeutic modalities.

Antibodies, Antinuclear↗

Nitrogen Nutrition of Nodules in Relation to ;N-Hunger' in Cowpea (Vigna unguiculata L. Walp).

Early growth, nodule development, and nitrogen fixation by two cultivars of cowpea (Vigna unguiculata L. Walp), one large-seeded (Vita 3; 146.0 +/- 0.9 milligrams seed dry weight, 4.1 +/- 0.2 milligrams seed N), the other small-seeded (Caloona; 57.5 +/- 2.5 milligrams seed dry weight, 1.8 +/- 0.1 milligrams seed N), were compared under conditions of sand culture with nutrient solution free of combined N. The seed stocks used had been obtained from plants uniformly labeled with (15)N, thus enabling changes with time in distribution of cotyledon and fixed N among plant parts to be measured by isotope dilution. Caloona, but not Vita 3, showed physiological symptoms of ;N hunger,' i.e. transient loss of chlorophyll (visible yellowing) and N from the first-formed unifoliolate leaves at or around the onset of symbiotic functioning and N(2) fixation. The smaller-seeded Caloona showed higher early nitrogenase activity than the larger-seeded Vita 3 and by 28 days had fixed 6.6 milligrams of N per milligram of seed N [mg N . (mg seed N)(-1)] versus only 3.5 mg N . (mg seed N)(-1) in Vita 3. Both cultivars lost around 30% of their initial seed N at germination, mostly as fallen cotyledons. Abscised cotyledons of Caloona contained 1.21 +/- 0.17% N; those of Vita 3 contained 2.61 +/- 0.37% N. When compared on the basis of cotyledon N available for seedling growth, Caloona was shown to have fixed 10.6 mg N . (mg seed N)(-1) and Vita 3 only 5.3 mg N . (mg seed N)(-1). Most of the cotyledon N withdrawn from the unifoliolate leaf pair of Caloona during ;N-hunger' was committed to early nodule growth and, in total, 20 to 25% of the cotyledon N resource of this cultivar was ultimately invested in establishment of symbiosis compared with only 7% in Vita 3.

Journal Article↗

Granulocytic sarcoma of the cervix as a primary manifestation: case without overt leukemic features for 26 months.

A case of granulocytic sarcoma involving the uterine cervix as primary manifestation without evidence of leukemia is presented. It was followed by neurological symptoms 19 months later and a right breast mass 26 months after the initial cervical lesion, but still with no evidence of leukemia. Two years and four months after onset, soft tissue and skin nodules developed and rare blastic cells appeared on peripheral blood smear. The patient terminally developed acute granulocytic leukemia with a rapidly downhill course. The differential diagnosis of granulocytic sarcoma and histiocytic lymphoma is discussed. The literature is reviewed with emphasis on the clinical and pathological problems that arise when the tumor presents in an unusual location without peripheral blood manifestation of leukemia.

Aged↗

Adjuvant and neoadjuvant chemotherapy with dacarbazine in high-risk childhood melanoma.

Four of four children with clinical Stage II-IIIB childhood melanoma treated at The University of Texas System Cancer Center M.D. Anderson Hospital with surgical excision of gross disease and adjuvant or neoadjuvant chemotherapy with dimethyl triazeno-imidazole carboxamide (dacarbazine) were alive without evidence of disease at 2, 6, 9.5, and 10.5 years after treatment. In one of the four patients suspected pulmonary nodules developed shortly after the start of chemotherapy, but regressed completely with continued treatment. In another patient with a primary left wrist melanoma and palpable epitrochlear and axillary nodes, there was dramatic shrinkage of nodal disease during chemotherapy and subsequent biopsies were cytologically negative. The expected survival of children with this rare condition when diagnosed at a comparably advanced stage and treated primarily by surgery is 32% compared with the 100% survival in these four cases. Although dacarbazine has not been notably successful as adjuvant therapy in high-risk adult melanoma, data from this small series is suggestive of an adjuvant effect in high-risk childhood melanoma and merits further study although the rarity of this condition may make a controlled trial difficult.

Child↗

Nodular form of bleomycin-related pulmonary injury in patients with osteogenic sarcoma.

Bleomycin (BLEO), an antitumor antibiotic effective against a variety of malignancies, has been associated classically with a pulmonary toxic reaction producing diffuse interstitial fibrosis. However, BLEO-related pulmonary nodules have been reported recently, mostly in children and young adults treated for germ cell tumors. A different, apparent hypersensitivity reaction with prominent eosinophilic infiltrates has been seen in other patients. This report details the clinical history, radiographic features, and histopathologic condition of three patients with osteogenic sarcoma in whom pulmonary nodules developed during the course of their multiagent, BLEO-containing chemotherapy. The predominant histopathologic lesion was bronchiolitis obliterans-organizing pneumonia (BOOP); one patient had a significant eosinophilic infiltrate also. Pulmonary lesions developed in all of these patients after relatively low doses of BLEO (less than 200 mg). All of these patients underwent open lung biopsy to establish the diagnosis. Reported cases of BLEO-induced pulmonary injury other than diffuse fibrosis are reviewed and comparisons are made with those in the current report. Also, suggestions are made for the management of these patients.

Adolescent↗

Retinoids and mammary gland differentiation.

Certain retinoids serve as effective chemopreventive agents against breast cancer. The effective retinoids are also antiproliferative agents for the mammary gland both in vivo and in vitro. N-(4-hydroxyphenyl)retinamide (HPR) can inhibit the occurrence of hyperplastic alveolar nodules in C3H mice in vivo and 7,12-dimethylbenz[a]anthracene-induced nodule-like alveolar lesions in vitro. Moreover, HPR can also inhibit the phorbol ester-induced promotion of hyperplastic alveolar nodule development in vitro. HPR is metabolized by the mammary gland in vitro and one of the metabolites competes for the cytosolic retinoic acid-binding protein although the metabolite is not all-trans-retinoic acid.

Animals↗

Rheumatologic manifestations of human parvovirus B19 infection in adults. Initial two-year clinical experience.

During 1987 and 1988, we identified 9 adults at the Medical and Rheumatology Services of the University of Iowa Hospitals and Clinics who had a clinical diagnosis of fifth disease; 8 of the 9 had symptoms of joint involvement. Another 12 adults with serologic positivity for anti-parvovirus B19 IgM antibody presented with polyarthralgia/polyarthritis. Patients were usually found to be seronegative for rheumatoid factor, and none developed nodules or erosive disease. Many patients with chronic disease met criteria for a diagnosis of rheumatoid arthritis. A diagnosis of parvovirus B19 infection should be considered during the initial visit of patients with polyarthralgia/polyarthritis.

Adult↗

Primary structure and differential expression of glutamine synthetase genes in nodules, roots and leaves of Phaseolus vulgaris.

In plants, glutamine synthetase (GS) is the enzyme primarily responsible for the assimilation of ammonia into organic nitrogen. In Phaseolus vulgaris a number of isoenzymic forms of GS are found, each of which consists of eight subunits of mol. wt 41 000-45 000. The GS subunits of P. vulgaris have previously been shown to be encoded by a small multigene family and a partial cDNA clone for a nodule-specific GS subunit has been obtained. We report here the isolation and nucleotide sequencing of two essentially full-length GS cDNA clones (pR-1 and pR-2) from a root cDNA library and the deduced amino acid sequences of the corresponding GS subunits (355 amino acid residues each). The coding sequences of pR-1 and pR-2 are closely related (80% nucleotide homology, 88% amino acid homology), but their 5'- and 3'-untranslated regions have diverged almost completely. Both pR-1 and pR-2 are related to, but distinct from, the nodule GS clone, pcPvNGS-01 (or pN-1). Hybridization to genomic Southern blots showed that the three GS mRNAs are encoded by three seperate genes and indicated the existence of a fourth class of GS gene. An S1 nuclease protection assay demonstrated the presence of R-1 and R-2 mRNA in both roots and leaves and confirmed that expression of the N-1 gene is nodule-specific. Expression of the R-1 and R-2 genes in the roots did not change significantly during nodulation. However, only the R-1 gene is expressed in the nodules themselves, indicating that the R-2 gene is specifically repressed during nodule development.

Journal Article↗

Transmembrane orientation and receptor-like structure of the Rhizobium meliloti common nodulation protein NodC.

The 46.8-kd NodC protein of Rhizobium meliloti is a membrane protein, essential for nodule formation. Gene fusions of nodC to a portion of the lambda cI repressor gene were used to define the membrane-anchor domain which is necessary for membrane insertion of the NodC protein into the membrane. The transmembrane orientation of NodC was confirmed by surface-specific radiolabeling and proteolysis experiments. A highly hydrophobic transmembrane-anchor domain was found near the carboxyl terminus, separating a large extracellular domain which contains an unusual cysteine-rich cluster from a short putative intracellular domain. Cross-linking studies showed that the NodC protein exists in the membrane probably as a dimer. The domain structure of the NodC protein shows striking similiarities with cell surface receptors. In nodules of various legumes a truncated form of the NodC protein was detected. The processed NodC was associated with the bacteroids and the amount of this protein increased during nodule development.

Journal Article↗

Signal molecules involved in plant embryogenesis.

In plant embryogenesis, inductive interactions mediated by diffusable signal molecules are most likely of great importance. Evidence has been presented that at late globular stages in plant embryogenesis, perturbation of the polar auxin transport results in abberrant embryo morphology. Rhizobium lipooligosaccharides or Nod factors are a newly discovered class of bacterial molecules that are able to trigger initial steps in root nodule development in legumes. Part of the activity of Nod factors may be directed towards alteration of endogenous plant growth regulator balance. The same bacterial Nod factors promoted the formation of globular embryos in the carrot cell line ts11. Whether there exist plant analogues of the Nod factors and whether these molecules are active as a more universal control system perhaps designed to initiate and or mediate gradients in auxin and cytokinin remains to be determined.

Cell Communication↗

Identification of two alfalfa early nodulin genes with homology to members of the pea Enod12 gene family.

In a search for plant genes expressed during early symbiotic interactions between Medicago sativa and Rhizobium meliloti, we have isolated and characterized two alfalfa genes which have strong sequence similarity to members of the Enod12 gene family of Pisum sativum. The M. sativa genes, MsEnod12A and B, encode putative protein products of 8066 Da and 12849 Da, respectively, each with a signal sequence at the N-terminus followed by a repetitive proline-rich region. Based on their expression during the initial period of nodule development, MsEnod12A and B are alfalfa early nodulin genes.

Amino Acid Sequence↗