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Diagnostic and prognostic significance of serum measurements of lactoferrin, lysozyme and myeloperoxidase in acute myeloid leukemia (AML): recognition of a new variant, high-lactoferrin AML.

92 patients with acute myeloid leukemia were classified according to the FAB classification (M1 n = 20, M2 n = 43, M3 n = 1, M4 n = 19, M5a n = 2, M5b n = 2, and M6 n = 5 patients). Serum measurements of lactoferrin (LF), myeloperoxidase (MPO) and lysozyme (LYS) were performed before the start of treatment. LF was significantly lower in M1 when compared with M2 but not as compared to M4, MPO was significantly higher in M2 and M4 than in M1, but comparable MPO levels were found in M2 and M4. LYS was significantly elevated in M2 in comparison with M1, and in M4 when compared to both M1 and M2. Polymorphonuclear granulocytes (PMNs) in M1 were significantly reduced when compared with M2 and M4, whereas mononuclear cells were significantly increased in M4 in comparison with both M1 and M2. FAB classification did not generate any prognostic information. When the patients were, instead, subdivided according to LF levels were found prognostically significant differences. Of patients below 100 micrograms/l, 44% went into remission as compared to 77% with LF from 101 to 400 micrograms/l. In patients with LF levels above 400 micrograms/l the remission frequency was only 14%. Multivariate statistical analysis on the data further suggested that lactoferrin may be used as an independent prognostic indicator. We conclude that although determination of the serum-levels of lactoferrin, lysozyme and myeloperoxidase in certain cases may be valuable as a supplement to the morphological examination of acute myeloid leukemia, it is evident that none of the three determinations can be used alone to distinguish between the FAB groups.

Adult↗

Genetic heterogeneity of hepatitis C virus: quasispecies and genotypes.

Worldwide, HCV is a major etiologic agent of chronic hepatitis that may lead to the development of liver cirrhosis and hepatocellular carcinoma. Thus, significant morbidity and mortality is caused by HCV infection and effective control measures against the spread of this virus are needed. Originally, the extent of genetic heterogeneity of HCV was not fully appreciated. However, the breadth of the genetic heterogeneity of HCV is great, and this may have important implications in diagnosis, pathogenesis, treatment, and vaccine development. In an infected individual the HCV genome population circulates as a quasispecies distribution of closely related yet heterogeneous RNA sequences centered around one dominant sequence. The dominant sequence, as well as the consensus sequence, changes sequentially during the course of the infection. A hypervariable region (HVR1) within one of the envelope proteins of HCV (E2) evolves very rapidly. Patients infected with HCV mount a humoral immune response to epitopes of HVR1. However, sequential changes in the consensus sequence of HVR1 during infection result in the generation of variants that are not recognized by preexisting antibodies. This might represent a mechanism by which HCV evades host immune surveillance and establishes and maintains persistent infection. It will be important to determine whether HVR1 of HCV, as was found for the V3 loop of HIV, contains epitopes that elicit neutralizing antibodies against HCV. Furthermore, it will be important to determine whether the quasispecies nature of HCV helps the virus evade the cytotoxic T-cell response of the host. Analysis of complete or partial HCV genomic sequences revealed that HCV exists as multiple, distinct genotypes. A total of nine major genetic groups and at least 30 subgroups have been recognized. To evaluate the current classification of HCV genotypes, we performed phylogenetic analyses of complete and partial nucleotide sequences from isolates that represent all published variants of HCV. Analysis of complete HCV sequences, which represent three major genetic groups, supports the currently used genotype classification scheme. However, analysis of the partial genomic regions (ie, C, E1, and NS5b) of HCV isolates that represent all recognized variants of HCV demonstrates that the genetic relatedness among some of the genotypes was not equivalent in the different gene regions. Furthermore, the distinction among isolates, subtypes, and types of HCV was not always clear. This finding might reflect the shortcomings of analyzing only limited gene regions or may reflect the wide spectrum of genetic variation of HCV.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A preliminary study of angiographic classification and its correlation to treatment of central arteriovenous malformation in the jaw.

OBJECTIVE: To elaborate on the classification of central arteriovenous malformations (AVMs) in the jaw based on angioarchitecture and to evaluate the correlation of this classification with treatment options. STUDY DESIGN: X-ray films and digital subtraction angiograms (DSA) of 25 cases with AVMs in the jaw were retrospectively reviewed to evaluate the appearance of bone resorption, feeding arteries, nidus of the malformations, and draining veins. Based on the findings a classification of angioarchitecture was recommended. Furthermore, the treatment results of these cases were reviewed to assess the correlation of this classification system with treatment options. RESULTS: The angiographic pictures of 25 cases with central AVMs could be divided into 5 types: Type I (n = 5) had diffused microarteriovenous fistulas (AVFs); type II (n = 8) had 1 large venous pouch with all the feeding arteries draining into it; type III (n = 7) had a large venous pouch as well as diffused microAVFs (I+II); type IV (n = 2) had multiple venous pouches; and type V (n = 3) had multiple venous pouches and diffused microAVFs (I + IV). The angioarchitecture corresponded well to the x-ray appearance in all cases except 1 (96%). With respect to the treatment outcomes, type II, III, and IV AVMs gained clinical cure in 100% of the cases, whereas type I and type V AVMs obtained clinical cure only in 60% and 33.3% of the cases, respectively. CONCLUSIONS: Central AVMs in the jaw contained variant patterns of angioarchitecture and could be divided into 5 types. This angiographic classification was helpful for decision making about appropriate therapy.

Adolescent↗

Reliable phenotyping of alpha-1-antitrypsin by hybrid isoelectric focusing in an ultranarrow immobilized pH gradient.

Genetically determined phenotypes of the highly polymorphic human alpha 1-antitrypsin were examined by hybrid isoelectric focusing in a narrow immobilized pH gradient. The chosen pH range from 4.45 to 4.75 was useful for identification and classification of the common PI M subtypes and a number of PI variants in the microheterogeneous regions of m6, m7, and m8. A high degree of resolution and an improved sharpness of PI bands was achieved with this excellent technique. It allowed the distinction of a new PI M variant, which has been designated M8, or Mingolstadt, according to the PI nomenclature. The pI difference of this mutant to the slightly cathodically located subtype M3 is approximately 0.001 pH unit. In addition, some common as well as rare phenotypes are presented.

Hydrogen-Ion Concentration↗

Acute myeloid leukemia (FAB-M2) with a masked type of t(8;21) translocation revealed by spectral karyotyping.

We report a case of acute myeloid leukemia (AML), M2 subtype according to the French-American-British (FAB) classification, with extramedullary myeloblastoma of the uterus and a masked type of variant translocation of t(8;21)(q22;q22). A 45-year-old Japanese woman presented with metrorrhagia, and AML (M2) with uterine invasion was diagnosed. The patient received an allogeneic peripheral blood stem cell transplantation after remission, and her pelvis was irradiated locally. Cytogenetic study at first showed t(8;17)(q22;p13) by G-banding. Spectral karyotyping (SKY) analysis modified this interpretation to a 3-way translocation involving chromosomes 8,17, and 21 and identified a masked type of variant t(8;21)(q22;q22) translocation. Results of fluorescence in situ hybridization using the AML1/ETO probe, and of detection of the AML1/ETO fusion transcript by reverse transcriptase-polymerase chain reaction were consistent with the karyotyping result. SKY analysis is useful to compensate for the limitations of cytogenetic studies.

Chromosomes, Human, Pair 21↗

[MR imaging of variants of the superior labral-bicipital complex and SLAP lesions].

In the detection of SLAP (superior labral anterior to posterior) lesions of the shoulder MR arthrography shows a significantly higher sensitivity compared with conventional MR techniques and therefore, represents the method of choice in diagnostic imaging of the superior labral-bicipital complex. On the basis of morphological criteria it mostly allows distinction of traumatic lesions and anatomic variants of the superior labrum and the biceps anchor as well as classification of detected SLAP lesions (types 1-4 according to Snyder). However, the differentiation of a SLAP type 2 lesion and a sublabral recess can be very difficult, even if all distinction criteria are considered.

Cartilage, Articular↗

Fractious cats and feline aggression.

Despite variation in terminology it is clear that the context in which feline aggression occurs is important for classification, prevention and treatment. Many of the aggressions discussed can be considered variants of normal feline behavior, so client education is particularly important. Educated clients will know when their cat can benefit from veterinary intervention, and when closing a door may be sufficient. The goals of treating all feline aggressions should be safety for all concerned, and quality of their living environment for the cats. The greater our knowledge, the more likely we are to achieve these goals.

Aggression↗

T-prolymphocytic leukaemia with spontaneous remission.

T-prolymphocytic leukaemia (T-PLL) is a rare dis-order with a poor prognosis. A 69-year-old man was diagnosed as having a small-cell variant of T-PLL according to the French-American-British classification by haematological, immunological and ultrastructural studies, although the cells had a CD7- phenotype and no chromosomal abnormality. He had no symptoms or organomegaly. The number of his lymphocytes, 53.7 x 109/l at the time of diagnosis, gradually decreased without therapy, and he was in complete remission 39 months later. A rearranged band in the T-cell antigen receptor-beta gene, which was detected at the time of diagnosis, decreased or disappeared. This is the first report of a T-PLL case with spontaneous complete remission.

Aged↗

[X-ray morphology and pathologic anatomy of osteoblastoma].

Between 1974 and 1984, 24 patients with osteoblastomas were entered in the bone tumour registry of the Gerhard Domagk Institute of Pathology and Institute for Clinical Radiology of Westphalia. These cases are evaluated. Osteoblastoma is a benign primary bone tumour with a peak incidence between ten and 20 years and a sex ratio of 18 males to 4 females in our series. The site of predilection is the spine (59%) with long bones in second place (32%). The tumor is mostly situated in the medulla. Radiologically it usually appears as a well demarcated translucency with a narrow rim and marginal sclerosis. Variations in radiological appearance and the histology and treatment are described. A malignant variant, the "aggressive osteoblastoma", is discussed and one case is described. The classification of these cases is considered.

Adolescent↗

Differential activation of "social" and "solitary" variants of the Caenorhabditis elegans G protein-coupled receptor NPR-1 by its cognate ligand AF9.

Natural variations of wild Caenorhabditis elegans isolates having either Phe-215 or Val-215 in NPR-1, a putative orphan neuropeptide Y-like G protein-coupled receptor, result in either "social" or "solitary" feeding behaviors (de Bono, M., and Bargmann, C. I. (1998) Cell 94, 679-689). We identified a nematode peptide, GLGPRPLRF-NH2 (AF9), as a ligand activating the cloned NPR-1 receptor heterologously expressed in mammalian cells. Shifting cell culture temperatures from 37 to 28 degrees C, implemented 24 h after transfections, was essential for detectable functional expression of NPR-1. AF9 treatments linked both cloned receptor variants to activation of Gi/Go proteins and cAMP inhibition, thus allowing for classification of NPR-1 as an inhibitory G protein-coupled receptor. The Val-215 receptor isoform displayed higher binding and functional activity than its Phe-215 counterpart. This finding parallels the in vivo observation of a more potent repression of social feeding by the npr-1 gene encoding the Val-215 form of the receptor, resulting in dispersing (solitary) animals. Since neuropeptide Y shows no sequence homology to AF9 and was functionally inactive at the cloned NPR-1, we propose to rename NPR-1 and refer to it as an AF9 receptor, AF9-R1.

Animals↗

Differential interactions among isolates of peanut stunt cucumovirus and its satellite RNA.

The interactions of seven isolates of peanut stunt cucumovirus (PSV) originating from North America, Europe and Africa, and two variants of PSV satellite RNA (sat RNA) were analysed. Electrophoretic and immunoblot analyses of the coat protein (CP) and Northern blot hybridization analyses of the viral RNAs showed that isolates PSV F352, 1339 and 1507 belonged to subgroup I, and isolates PSV W, Su and B to subgroup II. The seventh isolate, robinia mosaic virus (RoMV) clustered with subgroup I isolates by CP analysis, but was related to both subgroups by RNA hybridization analysis. The ability to support the accumulation of two newly described sat RNA variants, P4 and P6 sat RNAs, was not related to PSV isolate classification: neither PSV W nor RoMV were helper viruses for these PSV sat RNAs. Symptom modulation by both sat RNAs was the same: the presence of sat RNA did not modify the symptoms induced by subgroup I isolates but exacerbated the symptoms induced by subgroup II isolates in both tobacco and cowpea. Sat RNAs P4 and P6 contained 393 nucleotides, and differed only in three nucleotide substitutions. This resulted in marked differences in infectivity, level of accumulation and relative encapsidation between both the sat RNAs. Accumulation levels and relative encapsidation of sat RNAs was also affected by the isolate of helper virus.

Arachis↗

Emended phenotypic characterization of Prototheca zopfii: a proposal for three biotypes and standards for their identification.

A representative selection of Prototheca zopfii strains isolated from different environmental habitats or clinical cases was characterized in a polyphasic approach in order to assess their intraspecies taxonomic position. Recently, the recognition of distinct phenotypic clusters has been reported as the assignment of 'variants'. In the present study, 11 strains were compared by a number of phenotypic and genetic criteria, including growth characteristics, biochemical reactions and serotyping results. Based on emended standards for biotype identification, P. zopfii strains showed auxanographic differences and distinct assimilation patterns with respect to utilization of amino acids and glycerol. Serotyping by means of immunoblotting revealed that all isolates of variant II obtained from clinical cases, i.e. isolates from bovine mastitis or from human enteropathia, showed specific antigen patterns. They were found to be different from strains assigned to the other two variants with respect to their immunogenic antigens. Furthermore, comparison of partial 18S rDNA sequences confirmed distinct differences between the former variants. Based on these results, it is proposed that P. zopfii merits classification as a species comprising three biotypes.

Animals↗

Acute pustulosis of the legs in diverticulitis with sigmoid stenosis: an overlap between bowel-associated dermatosis-arthritis syndrome and pustular pyoderma gangrenosum.

BACKGROUND: Bowel-associated dermatosis-arthritis syndrome denotes the occurrence of diarrhoea with arthritis and skin lesions related to bowel disease with or without bowel bypass. In this condition, the histological finding of cutaneous aseptic neutrophilic cell infiltrate is non-specific and common to a wide spectrum of neutrophilic dermatoses, including pyoderma gangrenosum. OBSERVATION: We describe a 78-year-old woman with fever, abdominal discomfort and arthralgias, who developed grouped pustular lesions on her shins with histologically spongiform pustule formation. Aetiological assessment disclosed diverticular disease with sigmoid stenosis. CONCLUSION: Although clinical and histological features in our case fit the diagnosis of bowel-associated dermatosis-arthritis syndrome, they may also correspond to a pustular variant of pyoderma gangrenosum. Our observation raises the question of the nosological classification of bowel-associated dermatosis-arthritis syndrome within the spectrum of neutrophilic diseases.

Acute Disease↗

Sonographic prediction of malignancy in adnexal masses using an artificial neural network.

OBJECTIVE: To generate a neural network algorithm which computes a probability of malignancy score for pre-operative discrimination between malignant and benign adnexal tumours. DESIGN: A retrospective analysis of previously collected data. Information from 75% of the study group was used to train an artificial neural network and the remainder was used for validation. SETTING: The Gynaecological Ultrasound Research Unit at King's College Hospital, London. POPULATION: Sixty-seven women with known adnexal mass who had been examined using transvaginal B-mode ultrasonography and colour Doppler imaging with pulse spectral analysis immediately before surgery. The excised masses were classified histologically as benign (n = 52) or malignant (n = 15), of which three were borderline. METHODS: The variables that were put into the artificial neural network were: age, menopausal status, maximum tumour diameter, tumour volume, locularity, the presence of papillary projections, the presence of random echogenicity, the presence of analysable blood flow velocity waveforms, the peak systolic velocity, time-averaged maximum velocity, the pulsatility index, and resistance index. Histological classification, categorised as benign or malignant, was the output result. RESULTS: A variant of the back propagation method was selected to train the network. The overall architecture of the network with the best performance contained an input layer with four variables (age, time-averaged maximum velocity, papillary projection score and maximum tumour diameter), a hidden layer with three units and an output layer with one. The sensitivity and specificity at the optimum diagnostic decision value for the artificial neural network output (0.45) were 100% (95% CI 78.2%-100%) and 98.1% (95% CI 89.5%-100%), respectively. These values were significantly better than those obtained from the independent use of the resistance index, pulsatility index, time-averaged maximum velocity or peak systolic velocity at their optimum decision values (P < 0.01). CONCLUSION: Artificial neural networks may be used on clinical and ultrasound derived end-points to accurately predict ovarian malignancy. There is a need for a prospective evaluation of this technique using a larger number of patients.

Adnexal Diseases↗

Tumours in Iceland. 11. Malignant tumours of the thyroid gland. A histological classification and epidemiological considerations.

All malignant primary tumours of the thyroid gland submitted for histological diagnosis in Iceland during the 30 years 1955-1984, and available for review, were typed histologically according to the World Health Organization classification but also taking into account the more recent well recognized follicular variant of papillary carcinoma. A total of 480 thyroid tumours were classified with a female--to male ratio of 2.8 (367 females, 129 males). The age distribution is much what would be expected, the anaplastic type of carcinomas occurring in the elderly while papillary and follicular tumours occur over a much wider age range. The incidence of thyroid carcinomas in Iceland is about 2-3 times higher than in the other Nordic countries. This is largely due to an unusually high incidence of the papillary type of carcinoma. Overall, the papillary carcinoma accounted for 80% of thyroid malignancies. The tumours diagnosed incidentally at autopsy were about 20% of the entire material, and these tumours were only of the differentiated types of thyroid carcinoma. Even if the incidentally diagnosed tumours are excluded, the percentage of papillary tumours is 77% which is unusually high. The papillary type of carcinomas occasionally occurred in familial clusters in Iceland but not sufficiently to account for the unusually high incidence. Some of the possible etiological factors are discussed.

Age Factors↗

Testicular sertoli cell tumours and relative sub-types. Analysis of clinical and prognostic features.

INTRODUCTION: Sertoli cell tumours have a rare (0.4-1.5% of all testicular neoplasms) and heterogeneous pathology. The aim of this paper is to analyse the histological classification of Sertoli cell tumours, in order to assess if the three different histotypes--classic type, large cell calcifying Sertoli cell tumour (LCCSCT) and sclerosing Sertoli cell tumour (SSCT)--really present distinctive clinical and prognostic features. MATERIALS AND METHODS: The current literature was reviewed; Sertoli cell tumour clinical series and single case reports were searched and analysed. Hence, more than 200 classic Sertoli cell tumours, 48 LCCSCTs and only 12 SSCTs were found. The thirteenth SSCT has been found by us in a 34-year-old man. RESULTS: Every single sub-type presents clinical specific characteristics regarding age of onset, bilaterality, focality, abnormal hormone production, correlated systemic symptoms. Ultrasonographic findings, size and--above all--malignant potential. CONCLUSIONS: The precise classification of these tumours is not important only histologically: the currently recognised variants really differ in clinical presentation and course. Moreover, LCCSCTs can be further divided in two subgroups with very different clinical behaviour, those in older patients and those associated with well-known syndromes. These clinical and prognostic variables are of great importance when deciding on the therapeutical approach.

Adult↗

Morphologic study of carcinoid-like tumors and their relation to true carcinoids, using tumors of the breast as a model.

Two cases of an unusual type of infiltrating ductal carcinoma of the breast are presented. Both cases demonstrated a carcinoid-like pattern and were indistinguishable from carcinoid tumors of the breast by light microscopy. However, Grimelius stains and electron microscopic evaluation showed no evidence of membrane bound secretory granules. In regard to the prognostic significance and proper classification of carcinoids of the breast, awareness of carcinoid-like morphologic variants of infiltrating ductal or lobular carcinoma is important. It is also apparent that there is a spectrum of tumors which demonstrate some properties of true carcinoids, however, only the true carcinoids show a better prognosis and it serves no useful purpose to separate the rest of these tumors. The diagnosis of carcinoid tumors requires demonstration of secretory granules on electron microscopic examination or in special stains; conventional light microscopic studies alone are insufficient for this diagnosis. All these principles may be applied to carcinoid like tumors of other sites.

Aged↗

Functional characterization of melanocortin-4 receptor mutations associated with childhood obesity.

The melanocortin-4 receptor (MC4R) is a member of the rhodopsin-like G protein-coupled receptor family. The binding of alpha-MSH to the MC4R leads to increased cAMP production. Recent pharmacological and genetic studies have provided compelling evidence that MC4R is an important regulator of food intake and energy homeostasis. Allelic variants of MC4R were reported in some children with early-onset severe obesity. However, few studies have been performed to confirm that these allelic variants result in an impairment of the receptor's function. In this study, we expressed wild-type and variant MC4Rs in HEK293 cells and systematically studied ligand binding, agonist-stimulated cAMP, and cell surface expression. Six of the 11 mutants examined had either decreased (S58C, N62S, Y157S, C271Y) or no (P78L, G98R) ligand binding, with proportional impairments in [Nle4, d-Phe7]-alpha-MSH-stimulated cAMP production. Confocal microscopy confirmed that the observed decreases in hormone binding by these mutants are associated with decreased cell surface expression due to intracellular retention of the mutants. The other five allelic variants (D37V, P48S, V50M, I170V, N274S) were found to be expressed at the cell surface and to bind agonist and respond with increased cAMP production normally. The data on these latter five variants raise the question as to whether they are indeed causative of the obesity or not and, if so, by what mechanism. Our data, therefore, stress the importance of characterizing the properties of MC4R variants associated with early-onset severe obesity. We further propose a classification scheme for mutant MC4Rs based upon their properties.

Alleles↗