Sweet's syndrome and bronchiolitis obliterans organizing pneumonia.
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Biopsy↗
Biomedical subjects
J Serrano
Publications and source records attributed to J Serrano.
Atypical chronic graft-versus-host disease following interferon therapy for chronic myeloid leukaemia relapsing after allogeneic BMT.
We report a 54-year-old woman who received interferon alpha for haematological relapse of Ph-positive CML, 7 years after allogeneic BMT from an HLA-identical brother. Eighteen months after relapse, cytogenetic and molecular remission was achieved. She received interferon therapy for 25 months and it was discontinued when she developed skin lesions on her face and trunk, dysphagia and fever with respiratory failure and bilateral patchy airspace consolidation of the lung without microbiologic findings. Histologic features showed discoid lupus erythematosis, oesophagitis with pseudomembranes and a mixed pattern of lymphocytic bronchiolitis involving the alveoli and interstitial spaces all compatible with chronic GVHD. The patient was commenced on immunosuppressive therapy with complete clinical and radiological resolution. The available evidence supports an atypical presentation of chronic GVHD and suggests a role for interferon alpha in the pathogenesis of GVHD. To the best of our knowledge, this is the first case reported of severe chronic GVHD occurring during the course of interferon therapy for relapsed CML.
Antineoplastic Agents↗
Detection of myeloperoxidase by flow cytometry in acute lymphoblastic leukaemias with BCR-ABL gene rearrangement.
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Adolescent↗
Does the widespread use of proton pump inhibitors mask, complicate and/or delay the diagnosis of Zollinger-Ellison syndrome?
BACKGROUND: Proton pump inhibitors are potent acid suppressants which, at normal doses, can result in hypergastrinaemia in patients with idiopathic oesophageal reflux disease and in the control of symptoms in most patients with gastrinomas. Therefore, their use could delay or mask the diagnosis of gastrinoma. AIM: To investigate whether the widespread use of proton pump inhibitors masks or complicates the diagnosis of gastrinoma. SUBJECTS AND METHODS: Data from two centres with different referral criteria for suspected gastrinomas were analysed (Gastroenterology Unit, Rome, Italy and National Institutes of Health, Bethesda, MD, USA). The number of referrals and the number of new patients with gastrinoma diagnosed in the years prior to the widespread use of proton pump inhibitors (1986-1992) were compared with the numbers since proton pump inhibitors became widely available (1993-1998). RESULTS: The decrease in referral rate (P=0.0009) and the decrease in the annual rate of gastrinoma diagnosis (P=0.0020) at both centres correlated with the increased use of proton pump inhibitors. At the Italian centre, there was a 62% decrease in annual referrals (P < 0.0001) in the post-proton pump inhibitor period, relative to the pre-proton pump inhibitor period, whereas there was an increase in the rate of referral of other gastrointestinal endocrine tumours. The number of new cases of gastrinoma diagnosed decreased by 40%. At the US centre, the referral rate decreased by 28% (P=0.024) in the post-proton pump inhibitor period. There was also a 43% decrease in the number of new cases diagnosed annually in the post-proton pump inhibitor period (P=0.0012). There was a 2.6-fold increase in the post-proton pump inhibitor period in the percentage of referrals with a false diagnosis of gastrinoma as the cause of hypergastrinaemia (P=0.0040). CONCLUSIONS: In both referral centres, less patients have been referred with a possible diagnosis of gastrinoma and fewer new patients with gastrinoma have been diagnosed since proton pump inhibitors became widely available. These data support the conclusion that, since proton pump inhibitors have been released, the diagnosis of gastrinoma has been masked and will probably be delayed, with the result that patients with gastrinoma will be diagnosed at more advanced stages in their disease course.
Anti-Ulcer Agents↗
Genetic structure and distinctness of Apis mellifera L. populations from the Canary Islands.
The genetic structure of Apis mellifera populations from the Canary Islands has been assessed by mitochondrial (restriction fragment length polymorphisms of the intergenic transfer RNAleu-COII region) and nuclear (microsatellites) studies. These populations show a low level of genetic variation in terms of average number of alleles and degree of heterozygosity. Significant differences in the distribution of alleles were found in both data sets, confirming the genetic differentiation among some of the islands but not within them. Two mitochondrial haplotypes characteristic of the Canary Islands are found at high frequencies, although populations are introgressed by imported honeybees of eastern European C lineage. This introgression is rather high on Tenerife and El Hierro and low on Gran Canaria and La Gomera, whereas on La Palma it has not been recorded. The finding of microsatellite alleles characteristic of the eastern European lineage corroborates the genetic introgression. Phylogenetic analyses indicate that the Canarian honeybees are differentiated from other lineages and provide genetic evidence of their African origin.
Alleles↗
Light and ultrastructural immunocytochemical study of prolactin cells in ovine adenohypophysis. Influence of lactation and weaning.
The influence of lactation and weaning on the number, distribution, and structure of mammotroph cells (PRL cells) in ewes was studied using immunocytochemical procedures for light and electron microscopy, as well as morphometric and stereological techniques. The adenohypophyseal gland of 12 ewes of the Segureña breed at different stages of milk production and weaning were analysed, while the same organ of 3 ewes in anestrus served as control. During lactation, PRL cells increased in number and decreased in size. Ultrastructurally, these cells showed a well-developed rough endoplasmic reticulum (RER) and Golgi complex (GC), and large secretory granules. These findings point to increased synthesis and secretion activities during lactation, and a decrease after weaning. One day after weaning 'storage' cells increased in number, and crinophagy became evident 7 days after weaning, when the first 'inactive' cells were seen (10% of total cells). In anestrus these last cells represented 40% of the total, and showed scarce granules, signs of inactivity, lysosomes and lipid droplets.
Anestrus↗
Assessment of hematologic progenitor engraftment by complete reticulocyte maturation parameters after autologous and allogeneic hematopoietic stem cell transplantation.
BACKGROUND AND OBJECTIVES: Hematopoietic restoration after marrow ablation is initiated by the erythroid compartment. However, the absolute microscope counts or corrected percentage of reticulocytes have proven to be poor markers of hematopoietic engraftment. Some reports have highlighted the usefulness of automatic flow cytometry methods to determine highly fluorescent reticulocytes, or mean fluorescence index. In this series of 60 hematopoietic stem cell transplants, we sought the normal kinetics throughout the post-transplant period of the following reticulocyte maturing parameters: highly fluorescent reticulocytes (RETH), immature reticulocyte fraction (IRF), mean fluorescence index (MFI) and also mean reticulocyte volume (MRV). DESIGN AND METHODS: Sixty consecutive patients undergoing allogeneic bone marrow (30 cases) and autologous mobilized stem cell transplantation (30 cases) were studied. Parameters of reticulocyte maturation were measured every other day from the beginning of the conditioning regimen until myeloid engraftment. RESULTS: Nadir values for the analyzed reticulocyte parameters were found between days +4 and +7 and thereafter, increases in these reticulocyte parameters appeared earlier than the rise in neutrophils. We considered erythroid engraftment to have occurred on the day when RETH reached 3%, IRF 10%, MFI 10 and MRV 110 fL. These cut-offs were assigned considering the 25% quartile for each parameter on the day that the myeloid engraftment occurred. The median engraftment days for RETH were +9 and +16, for IRF +9 and +13, for MFI +9 and +13 and for MRV +11 and +13 in autologous and allogeneic procedures, respectively. When compared to standard neutrophil engraftment, IRF and MFI engraftment occurred significantly earlier in all patients. Remarkably, we found a statistical correlation between the day a reticulocyte parameter reached its cut-off and the subsequent day of absolute neutrophil count (ANC) recovery for MFI after allogeneic transplants and for MRV after autologous procedures (p < 0.001 and p= 0.02, respectively). Of all the clinical parameters tested, only the number of infused CD34 cells showed a statistical influence on erythroid engraftment in autologous transplant. INTERPRETATION AND CONCLUSIONS: Early reticulocytes appear sooner than neutrophils after both autologous and allogeneic transplants, and any determined reticulocyte parameter can reliably measure this fraction. Nevertheless, our results show that MRV and MFI cut-offs are useful for determining subsequent myeloid engraftment. These findings could be relevant to decision-making in those patients with primary graft failure heralded by an absence of increasing values of MFI and MRV, indicating very low production of reticulocytes from the graft, who could, therefore, benefit from earlier rescue therapy.
Adolescent↗
IgA and IgM anti-Naegleria fowleri antibodies in human serum and saliva.
Antibodies from IgA and IgM classes that recognize Naegleria fowleri (Nf) proteins were detected by the ELISA assay in serum and saliva from three groups of people: (i) subjects with upper respiratory tract infections (URTI) living in the parasite-endemic area, (ii) healthy persons from the same area, and (iii) healthy persons from a parasite-nonendemic area. In serum and in saliva the titers of IgA antibodies to Naegleria fowleri in the group of patients with URTI was significantly higher than that of the healthy group in the parasite-endemic area; also the titers of IgM antibodies in serum were significantly higher in patients. On the contrary, in saliva the antibodies were higher in healthy people from the parasite-endemic area. In all cases the subjects from the parasite-nonendemic area had lower antibody titers in serum and saliva.
Adult↗
Her-2/neu oncogene expression in Puerto Rican females with breast cancer.
Her-2/neu belongs to the family of tyrosine kinase transmembrane proteins whose overexpression has been associated with a poor prognosis in patients with breast cancer. The product of this proto-oncogene is overexpressed in 25-30% of human breast cancer and is the target of selective immunotherapy. Concerned about the ethnic differences on the expression of this oncogene, we have evaluated 143 consecutive specimens of primary breast cancer diagnosed in San Pablo Hospital, Puerto Rico. The specimens were analyzed for Her-2/neu expression using immunohistochemistry assays (Hercept test). We have related the expression of hormone receptor status, percent cells in S phase, DNA ploidy, tumor size, nodal status and menopausal state with the Her2/neu expression. Out of 143 specimens, 28 overexpressed the Her-2/neu (19.6%). Of the Her/2 negative 30/114 (26%) were estrogen receptor negative as compared to 9/27 (33%) (p = 0.464). The degree of aneuploidy was abnormal in 25/104 (24%) in the Her-2/neu negative vs 11/27 (41%) p = 0.083. The percent cell in DNA synthesis was high in 16/77 (21%) in Her-2/neu negative vs 4/15 (27%) p = 0.613. The tumor size was greater than 2 cm in 35/106 (33%) in Her-2/neu negative vs 9/23 (39%) p = 0.575. In the progesterone specimens negative for Her2, 44/114 (39%) were Her2/neu negative vs 15/27 (56%) p = 0.108. No differences were seen regarding menopausal status, age and nuclear grading. A trend favoring abnormal aneuploidy in Her2/neu positive was seen. Nodal involvement was significantly associated with Her2/neu overexpression. (p = 0.037). Although the incidence of Her2 overexpression found in this database was somewhat lower than the one reported in the literature, this might also be due to the small cohort examined or to the technique utilized.
Adenocarcinoma↗
Molecular analysis of lineage-specific chimerism and minimal residual disease by RT-PCR of p210(BCR-ABL) and p190(BCR-ABL) after allogeneic bone marrow transplantation for chronic myeloid leukemia: increasing mixed myeloid chimerism and p190(BCR-ABL) detection precede cytogenetic relapse.
We studied lineage-specific chimerism and minimal residual disease (MRD) in sequential posttransplant samples from 55 patients who underwent unmanipulated (n = 44) or partially T-cell-depleted (n = 11) allogeneic bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Chimerism was assessed by polymerase chain reaction (VNTR [variable number of tandem repeats]-PCR) analysis in highly purified CD19+, CD3+, CD15+, and CD56+ cell fractions, whereas MRD was investigated in whole blood by reverse transcriptase-PCR (RT-PCR) of both p210(BCR-ABL) and p190(BCR-ABL) hybrid transcripts. Of 55 patients, 14 (including 6 T-cell-depleted patients) had cytogenetic relapse at 5-80 months and progressed to hematologic relapse, while 41 patients remained in prolonged cytogenetic remission 12-107 months post-BMT. Before leukemia recurrence, patients in the relapse group showed a consistent evolution pattern sequentially featured by persistent p210(BCR-ABL) positivity, increasing mixed chimerism (MC) in myeloid cells, p190(BCR-ABL) positivity, and, finally, cytogenetic relapse. Myeloid MC preceded cytogenetic relapse by 2-12 months, whereas p190(BCR/ABL) was detected 1-6 months prior to cytogenetic relapse in 11 patients and concomitant with cytogenetic relapse in 3 patients. In the remission group, all patients invariably tested negative for p190(BCR-ABL); 10 patients tested positive for p210(BCR-ABL) at variable time-points but showed persistent full donor chimerism (DC), whereas 31 patients tested p210(BCR-ABL) negative and displayed full DC or transient MC due to the persistence of recipient T cells. Two patients in the relapse group were successfully reinduced into molecular remission with donor lymphocyte infusion. Sequential molecular analysis after such treatment showed the inverse pattern to that observed prior to relapse, ie, progressive disappearance of p190(BCR-ABL) transcripts, conversion of myeloid chimerism to donor type, and, finally, p210(BCR-ABL) negativity. We conclude that lineage-specific chimerism and p190(BCR-ABL) messenger RNA (mRNA) analyses contribute a better characterization of CML evolution after BMT and enable early identification of patients at the highest risk of relapse. (Blood. 2000;95:2659-2665)
Adolescent↗
[All that glitters is not gold].
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Terminology as Topic↗
Distribution of adrenomedullin-like immunoreactivity in the rat central nervous system by light and electron microscopy.
Adrenomedullin is a peptide of marked vasodilator activity first isolated from human pheochromocytoma and subsequently demonstrated in other mammalian tissues. Using a polyclonal antiserum against human adrenomedullin-(22-52) amide and the avidin-biotin peroxidase complex technique, we have demonstrated by light and electron microscopy that adrenomedullin-like immunoreactivity is widely distributed in the rat central nervous system. Western blotting of extracts of different brain regions demonstrated the fully processed peptide as the major form in the cerebellum, whereas a 14-kDa molecular species and a small amount of the 18-kDa propeptide were present in other brain regions. Immunoreactive neurons and processes were found in multipolar neurons and pyramidal cells of layers IV-VI of the cerebral cortex and their apical processes, as well as in a large number of telencephalic, diencephalic, mesencephalic, pontine and medullary nuclei. Cerebellar Purkinje cells and mossy terminal nerve fibers as well as neurons of the cerebellar nuclei were immunostained, as were neurons in area 9 of the anterior horn of the spinal cord. Immunoreactivity was also found in some vascular endothelial cells and surrounding processes that probably originated from perivascular glial cells. Electron microscopy confirmed the light microscopy findings and showed the reaction product in relation to neurofilaments and the external membrane of small mitochondria. Immunoreactive terminal boutons were occasionally seen. The distribution of adrenomedullin-like immunoreactivity in the central nervous system suggests that it has a significant role in neuronal function as well as in the regulation of regional blood flow.
Adrenomedullin↗
Identical clonality of sporadic gastrinomas at multiple sites.
Gastrinomas are neuroendocrine neoplasms that occur sporadically and in patients with multiple endocrine neoplasia type 1 (MEN1). In MEN1, multiple gastrinomas have been shown to arise by independent clonal events (Debelenko, et al., Cancer Res., 57: 2238-2243, 1997). The purpose of the present study was to analyze clonality in 20 sporadic gastrinomas from eight patients in whom the tumor was present in at least two separate sites. A combination of methods was used to assess clonality, including MEN1 gene mutation analysis, loss of heterozygosity analysis of the MEN1 locus, and analysis of X-chromosome inactivation at the human androgen receptor locus (human androgen receptor analysis). In three patients, a somantic MEN1 gene mutation was detected in the tumor. Identical mutations were found in other tumors at different sites within the same patients. Human androgen receptor analysis in three informative patients and loss of heterozygosity analysis in five patients revealed identical clonal patterns in the tumors from multiple sites in each patient. We conclude that sporadic gastrinomas at multiple sites are monoclonal and that MEN1 gene alterations in gastrinomas occur before the development of tumor metastases.
Adult↗
Characterization of dansylated glutathione, glutathione disulfide, cysteine and cystine by narrow bore liquid chromatography/electrospray ionization mass spectrometry.
A method using reversed phase high performance liquid chromatography/electrospray ionization-mass spectrometry (RP-LC/ESI-MS) has been developed to confirm the identity of dansylated derivatives of cysteine (C) and glutathione (GSH), and their respective dimers, cystine (CSSC) and glutathione disulfide (GSSG). Cysteine, GSH, CSSC and GSSG are present at low concentrations in rainbow trout (Oncorhynchus mykiss) liver cells. Initially, hepatic cells were sampled from a suspension culture and disrupted upon addition of 10% perchloric acid. The reduced thiols present in the cell extracts were acetylated to prevent dimerization and then the C and GSH species were derivatized with dansyl chloride for fluorescence detection. An LC system using a weak anion exchange column (AE) with fluorescence detection (FLD) was used for sensitive routine analysis; however, it produced peaks of unknown origin in addition to the expected analytes. Analytes were then separated on a C18 RP-LC system using a water/acetonitrile gradient with 0.2% formic acid, and detected using LC/ESI-MS at 3.5 KV which produced an intense ion with a minimum limit of detection of less than 0.5 pmole injected (>10:1 signal-to-noise (S/N). Subsequently, fractions of effluent from the AE-LC/FLD system were analyzed by LC/ESI-MS to confirm the presence of the target analytes in routine cell extracts. Monodansylated GSSG was identified as a product that could possibly affect the quantification of GSH and GSSG.
Animals↗
Myeloperoxidase gene expression in non-infant pro-B acute lymphoblastic leukaemia with or without ALL1/AF4 transcript.
In this study, we examined myeloperoxidase (MPO) gene expression in a series of 31 non-infant pro-B acute lymphoblastic leukaemia (ALL) patients that included 16 cases with the t(4;11) translocation and/or the resultant ALL1/AF4 chimaeric gene. Sixteen out of 31 cases (51%) were MPO mRNA positive/enzyme negative. MPO mRNA was detected in nine out of 16 (56%) and seven out of 15 (47%) patients with and without the ALL1/AF4 fusion transcript respectively. The comparative study between MPO mRNA positive and negative cases showed statistically significant differences with regard to age and white blood cell (WBC) count, and was 39.5 years vs. 26.3 years (P = 0.016) and 71.4 x 10(9)/l vs. 157.8 x 10(9)/l (P = 0.046) in the MPO mRNA positive and negative groups respectively. The correlation analysis between MPO mRNA expression, age, WBC count and leukaemic relapse according to the presence/absence of the ALL1/AF4 fusion showed that the statistically significant differences observed in the whole group were related mostly to the ALL1/AF4-positive ALL patients. In fact, in this latter group, the mean WBC count and patients' age were 85 +/- 79 x 10(9)/l vs. 289.8 +/- 102 x 10(9)/l (P = 0.0005) and 44.8 +/- 15.3 years vs. 26.7 +/- 13.7 years (P = 0.01) in patients with and without MPO mRNA expression respectively. It appears, therefore, that the assessment of MPO mRNA expression enables a further dissection of leukaemia heterogeneity in apparently homogeneous genetic/immunophenotypic ALL subsets.
Adolescent↗
Light and ultrastructural immunocytochemical study of somatotropic cells (GH cells) in ovine adenohypophysis: lactation and weaning influences.
The influence of lactation period and weaning on the distribution, number, and structure of somatotropic cells (GH cells) in ewes was studied using immunocytochemical procedures for light and electron microscopy, as well as morphometric and stereological techniques. The adenohypophyseal gland of 12 ewes of the Segureña breed in different stages of milk production and weaning was studied, while three ewes in anoestrus served as controls. The size of secretory granules was heterogeneous in all stages, suggesting that this characteristic is not related to functional activity. During lactation and weaning the size of GH cells decreased, while the number of 'synthesis cells' increased. The rough endoplasmic reticulum and Golgi complex appeared more developed and small secretory granules showed lower gold particle labelling. These data suggest that GH cells are more active during lactation, particularly during late lactation.
Animals↗
Pigmented villonodular synovitis of the wrist invading bone--a report of 2 cases.
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Adult↗
Variability in rDNA loci in Iberian species of the genus Zabrus (Coleoptera: Carabidae) detected by fluorescence in situ hybridization.
Fluorescence in situ hybridization (FISH) with a PCR-amplified 18S ribosomal probe was used to map rDNA loci in 19 taxa of the ground beetle genus Zabrus (2n = 47-63) from the Iberian Peninsula. A quantitative and qualitative variation has been observed among related species, subspecies, populations, and even individuals. The number of rDNA-carrying chromosomes varies from 2 to 12, and the extent of the signal from small dots to entire arms. Changes altering the number of rDNA clusters seem to be uncoupled from the variation found in the chromosome number. Mechanisms that explain the numerical variation and spreading of rDNA clusters throughout the genome within the genus Zabrus are briefly discussed. No concordance between the pattern of rDNA sites and the phylogenetic relationships as based on morphological characters has been found.
Animals↗