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PubMed1997

Cytohistological and immunological classification of canine malignant lymphomas: comparison with human non-Hodgkin's lymphomas.

Non-Hodgkin's lymphomas (NHLs) in man are on the increase. They are also common in dogs, which, as close companions of man, may constitute a useful experimental model. However, comparisons cannot be made without a reliable morphological and immunological classification of canine NHL. Canine NHLs (n = 134) were classified on the basis of fine-needle lymph-node aspirates according to the Kiel classification, and 92 were re-classified according to the Working Formulation and the updated Kiel classification, in a histological and immunological study. The immunophenotype was determined (1) in 92 cases by the use of the pan-T anti-CD3 polyclonal antibody and the pan-B anti-mb1 monoclonal antibody on paraffin wax-embedded tissue sections, and (2) in 47 cases by the use of a panel of polyclonal and monoclonal antibodies on fresh preparations and frozen tissue. Cytological analysis showed a predominance of high-grade lymphomas (73.9%) over low-grade lymphomas (26.1%); it also demonstrated forms not reported in other species (small-cell variants, lymphomas with macronucleolated medium-sized cells [MMCs], and polymorphic lymphomas with a centroblastic component). Histological examination revealed the rarity of follicular lymphomas (2.2% of cases), an appearance suggestive of T-cell neoplasia (8.7% of cases), and evidence that some MMC lymphomas originated in the marginal perifollicular zones. Some (26%) of the lymphomas were of the T-cell phenotype: the majority of these consisted of small-cell, low-grade lymphomas and mycosis fungoides, the rest being either high-grade pleomorphic lymphomas (mixed or large-cell) or, rarely, high-grade, small noncleaved-cell, plasmacytoid lymphomas. No lymphoma expressed a double (T and B) phenotype. This study revealed similarities with, but also notable differences from, human NHL. In particular, the MMC lymphomas may constitute an interesting equivalent of human marginal zone B-cell lymphomas.

Animals↗
PubMedDate not supplied

[Diagnosis and genetics of congenital dyserythropoietic anemias (CDA)].

The congenital dyserythropoietic anemias (CDA) are hereditary diseases characterized by a lifelong, mostly moderate anemia. CDA can be diagnosed already in early childhood. However, diagnosis is complicated due to poor knowledge of morphological criteria and the large number of differential diagnoses that have to be excluded. CDA type I is characterized by macrocytic anemia with megaloblastic changes in erythropoiesis and chromatin bridges between isolated erythroblasts. Type II shows a normocytic anemia with a positive acidified serum test and increased agglutination with anti-i. Erythroblasts can present with 2 or more nuclei. CDA type III presents with a macrocytic anemia and erythroblasts with up to 12 nuclei, the so called gigantoblasts. Some patients lack the typical morphological abnormalities of type I-III (variants or type IV). Besides light microscopic abnormalities, CDA type-specific changes in electron microscopy are described. The clinical picture of the patients vary between the different forms: signs of hemolysis and ineffective erythropoiesis such as icterus, splenomegaly and gall stones can be present. Most important is the tendency of a part of patients to have an increased iron absorption and iron storage. Patients with and without transfusion dependency are described. Supportive care such as iron chelation can be necessary in some patients. The CDA are inherited in an autosomal recessive manner; in type III an additional autosomal dominant variant exists. Recently, the determination of gene loci for type I, II and III was enabled by linkage analysis on different regions of chromosome 15 and 22. It is considered that CDA I and II are genetically heterogenic. Until now no gene has been identified in either type of CDA. In CDA type II, a glycosylation defect of erythrocyte membrane proteins is present. An international group plans to do further research. Therefore, identification and registration of patients in a registry is necessary. Patients' data and material would enable gene characterization. The results would allow an extended classification according to genotype and prediction of the course of the disease. Additionally, information on the regulation and control of normal and abnormal erythropoiesis could be obtained.

Anemia, Dyserythropoietic, Congenital↗
PubMed2003

Implementing DRGs in Slovenia: why the Australian variant was selected.

Slovenia is embarking on an ambitious health sector reform program, a small part of which involves implementing the categorization of acute inpatients by DRG for payment purposes. I summarise the leading DRG variants, and describe the process of selecting one of them. I argue that the Slovenian decision to use the Australian DRG variant as a starting point was sensible in terms of cost, speed of implementation, and usefulness of the resultant information. More time and effort could have been spent on the appraisal process, but I suspect it would not have led to a different outcome.

Australia↗
PubMed2004

Class discovery and classification of tumor samples using mixture modeling of gene expression data--a unified approach.

MOTIVATION: The DNA microarray technology has been increasingly used in cancer research. In the literature, discovery of putative classes and classification to known classes based on gene expression data have been largely treated as separate problems. This paper offers a unified approach to class discovery and classification, which we believe is more appropriate, and has greater applicability, in practical situations. RESULTS: We model the gene expression profile of a tumor sample as from a finite mixture distribution, with each component characterizing the gene expression levels in a class. The proposed method was applied to a leukemia dataset, and good results are obtained. With appropriate choices of genes and preprocessing method, the number of leukemia types and subtypes is correctly inferred, and all the tumor samples are correctly classified into their respective type/subtype. Further evaluation of the method was carried out on other variants of the leukemia data and a colon dataset.

Algorithms↗
PubMed2025

Polygenic Risk Scores and HLA Class II Variants are Biomarkers of Corticosteroid Response in Childhood Nephrotic Syndrome.

INTRODUCTION: Nephrotic syndrome (NS), a common glomerular disease in children, is classified based on response to corticosteroid therapy as either steroid-sensitive nephrotic syndrome (SSNS), or steroid-resistant nephrotic syndrome (SRNS). However, there are currently no reliable predictors of therapy response at initial clinical presentation. METHODS: We conducted genome-wide association studies, developed polygenic risk scores (PRS) for therapy response and analyzed classical HLA alleles in 1,997 (994 discovery and 1,003 replication/validation cohorts) previously unstudied children with NS and 3,558 ancestry-matched controls. RESULTS: A significant association with HLA loci defined by variants in HLA-DQB1, HLA-DRB1, and HLA-DQA1 were found for SSNS (but not SRNS), along with a second immune-related SSNS locus: CLEC16A. A PRS that discriminates between SSNS and SRNS was validated in two independent cohorts. The HLA haplotype HLA- DRB1*07:01~DQA1*02:01~DQB1*02:02 was associated with ~4 times the risk of developing SSNS. A model incorporating HLA haplotype, PRS score, and age at onset of the disease was the best predictor of steroid responsiveness with an AUC of 0.68-0.70 and an overall classification accuracy of SSNS versus SRNS of 67-71%. CONCLUSIONS: Our findings confirm that SSNS (unlike SRNS) is an immune-mediated HLA-associated disorder. The PRS for therapy response and HLA haplotype can serve as biomarkers and provide a foundation for more accurate diagnoses and tailored and individualized treatment.

HLA haplotype↗
PubMed1996

Mixed medullary-follicular carcinoma of the thyroid gland: a clinicopathologic variant of medullary thyroid carcinoma.

A rare case of mixed medullary-follicular carcinoma of the thyroid gland, which occurred in a 44-year-old man, is reported. The thyroid tumor was composed of solid nests of polygonal cells, with an admixture of many evenly distributed thyroid follicles that contained colloid. The lymph node metastases were the same composition as the primary, with follicle formations that contained colloid. Immunohistochemically, in both the primary and metastatic lesions, calcitonin and carcinoembryonic antigen were present in the predominant solid areas of medullary carcinoma, whereas thyroglobulin was demonstrated in the follicular structures. At the ultrastructural level, most of the tumor cells contained numerous neurosecretory granules, but some showed follicular cell differentiation. These findings fulfilled the criteria of mixed medullary-follicular carcinoma of the thyroid according to the World Health Organization classification and also suggested dual neuroendocrine and follicular differentiation of this type of thyroid carcinoma. We reviewed the literature on mixed medullary-follicular carcinoma of the thyroid and concluded that it might constitute another clinicopathologic entity different from conventional medullary thyroid carcinoma; it occurs predominantly in younger males and is associated with a more favorable clinical course than the usual medullary thyroid carcinoma.

Adenocarcinoma, Follicular↗
PubMed1996

HIV type 1 phenotype correlates with the stage of infection in vertically infected children.

A cohort of 39 vertically infected children (class N, A, B, and C of the CDC HIV classification for pediatric infection) was studied by virus isolation and non-syncytium inducing (NSI)/syncytium inducing (SI) HIV-1 phenotype evaluation. The HIV-1 isolates were recovered from PBMCs and the MT-2 cell line was used to perform the syncytium assay. HIV-1 could be isolated in 34 of 39 (87%) infected children, regardless of the clinical and immunological stage of the disease. Class N and A subjects harbored exclusively NSI strains, whereas the SI phenotype was detected in two of eight class B and five of nine class C patients. All of the SI variants were observed in severely CD4-depleted children (class 3 patients). The capability of pediatric HIV-1 isolates to induce a cytopathic effect is associated with the clinical status and the degree of CD4 depletion. These data suggest that the biological properties of HIV-1 isolates in children do not differ from those observed in adults, and that viral phenotype strictly correlates with disease progression in vertically infected children.

Cell Line↗
PubMed1987

Severe combined immune deficiency due to a homozygous 3.2-kb deletion spanning the promoter and first exon of the adenosine deaminase gene.

We have investigated the structural gene for adenosine deaminase (ADA) in a female infant with ADA deficiency associated severe combined immune deficiency (ADA-SCID) disease and her family by DNA restriction-fragment-length analysis. In this family a new ADA-specific restriction-fragment-length variant was detected, which involves a 3.2-kb deletion spanning the ADA promoter as well as the first exon. It was found that the patient, who was born to a consanguineous couple, was homozygous and both her parents and her brother were heterozygous for the deletion. No ADA-specific mRNA could be detected by hybridization in fibroblasts derived from this patient. Thus the patient was established to be homozygous for a true null ADA allele. In the light of the apparently normal development of most tissues except the lymphoid tissue the above finding directly questions the classification of ADA as a 'housekeeping' enzyme.

Adenosine Deaminase↗
PubMed1994

Epidemiology of the rheumatic diseases.

Understanding, description, and classification of musculoskeletal pain syndromes have been further substantiated, but linking them to physical and psychological variables remains problematic. Core tools to measure disability in a population context forms a stable, well validated set of instruments, which increasingly has been translated, tested, and applied in sociocultural settings and in outcome research. Evidence for a declining incidence of rheumatoid arthritis seems established, and paleopathologic evidence indirectly provides some support for a possible causative environmental agent. Within an epidemiologic framework, immunogenetic studies continue to suggest an increasing number of subsets of rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis variants. Studies in which the overuse hypothesis was tested as a cause in the etiology of osteoarthritis have provided conflicting results. Increasing evidence shows a secular trend in loss of bone mineral density, resulting in an increased fracture incidence. However, validated methods to safely prevent osteoporosis and fracture are also being established. Finally, although they are now well recognized and scientifically productive, large long-term epidemiologic studies should be critically examined.

Persons with Disabilities↗
PubMed1995

Chemotherapy for AIDS-related and endemic African Kaposi's sarcoma in southern Africa.

BACKGROUND: Kaposi's sarcoma (KS), either in its endemic (African) form or its AIDS-related variant, is a common neoplastic disorder seen in Southern Africa. Chemotherapy has been proven to be very effective in advanced or relapsed African Kaposi's sarcoma, but much less so in AIDS-related, endemic KS. PATIENTS AND METHODS: The study consists of a retrospective analysis of the results of chemotherapy alone in 17 patients with African KS (AKS) and in 32 patients with epidemic AIDS-related KS (EKS), treated at the Johannesburg General Hospital between 1982 and 1992. Single agents included vinblastine, actinomycin D, bleomycin, and vincristine; combined regimens were largely doxorubicin/vincristine/bleomycin or etoposide/methotrexate. Outcome classifications were: complete remission (CR), partial remission (PR), and treatment failure (TF). RESULTS: Four of the 17 patients with AKS had CR, 10 a PR, and three were TF and died rapidly from their disease. The combined chemotherapeutic regimens produced marked symptomatic relief and even long-term remission in AKS. In patients with EKS, the response rate to chemotherapy was very low and of brief duration. No patient had a CR and debilitating side effects were common. CONCLUSIONS: The African type of AKS is a chemo-sensitive tumor, whereas the endemic type EKS, like its Western counterpart, has a dismal prognosis.

AIDS-Related Opportunistic Infections↗
PubMed1986

Invasive lobular carcinoma of the breast. An analysis of 29 cases.

Twenty-nine cases of invasive lobular carcinoma were analyzed, based on three aspects of the histology: 1) cellular features such as a monotonous proliferation of uniform small cells, 2) a single file or targetoid arrangement, and 3) loss of cell cohesion or dissociation of tumor cells. Twenty-four tumors which fulfilled these three criteria were appraised as cases of conventional lobular carcinoma, in a classic sense, while five others were a variant of this tumor. Individual tumor cells of lobular carcinoma were estimated to be well differentiated, both morphologically and functionally, revealing well developed intracytoplasmic organelles and a high percentage of alpha-lactalbumin content in the cytoplasm. Nevertheless, the tumor itself was characterized by a lack of any particular structural differentiation in the arrangement of cells. Based on the observation of the histologic features, invasive lobular carcinoma was subclassified into three groups, in situ predominant, intermediate, and diffuse infiltrating and with a definite correlation to the age of the patient and to the prognosis. Validity of this classification indicates that lobular carcinoma progresses gradually, even in the invasive phase, and can be categorized as a slowly growing subset of mammary carcinoma.

Adult↗
PubMed1997

Prostaglandin levels of primary bone tumor tissues correlate with peritumoral edema demonstrated by magnetic resonance imaging.

BACKGROUND: Several reports have shown peritumoral edema accompanying primary bone tumors demonstrated by magnetic resonance imaging (MRI). However, the mechanism of this inflammatory reaction is still unclear. The authors postulated that the reaction was caused by some chemical mediators including prostanoids, because several investigators have observed that some types of bone tumors synthesize prostanoids. Therefore, the authors compared MRI findings and tumor prostaglandin (PG) levels. METHODS: The subjects were 29 patients with primary bone tumor or tumor-like conditions: chondroblastoma (n = 5); chondrosarcoma, including rare variants (n = 8); giant cell tumor (n = 6); osteochondroma (n = 5); osteoblastoma (n = 2); Ewing's sarcoma (n = 2); and eosinophilic granuloma (n = 1). T1- and T2-weighted spin echo images were obtained in all but one patient before surgery. The tumor concentration of prostaglandin E2, 6-keto-PGF1 alpha, and thromboxane B2 were measured by radioimmunoassay. RESULTS: MRI distinctly showed bone marrow edema in 9 and soft tissue edema in 12 of the 28 patients examined. These findings were significantly correlated with the PG levels. Moreover, the PG levels were correlated with the histologic classifications (P < 0.001). In particular, the chondroblastomas showed prominent concentrations of PGs compared with other cartilaginous tumors or giant cell tumors. CONCLUSIONS: Although peritumoral edema accompanying benign and malignant bone tumors is not necessarily related to one single pathophysiologic mechanism, these results suggest that PG production was an important cause of the inflammatory reaction that was revealed by MRI. Recognition of this phenomenon is advantageous not only for strict diagnostic purposes but also for understanding the characteristic features of individual primary bone tumors.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Small round viruses: classification and role in food-borne infections.

Since the first observation of Norwalk virus in the electron microscope in 1972, many different small virus particles in the size range 20-40 nm have been described world-wide in association with outbreaks of gastroenteritis. Progress characterizing these agents has been hampered by the relatively small numbers of particles present in clinical material and the lack of success in culturing them. Although the relationship between some of these viruses remains confusing, a number of distinct groups has emerged, based on morphological features and limited physical data. Immuno-electron microscopy has proved valuable in detecting viruses but the addition of antibody can mask surface morphological features. Examination of viruses in negatively stained preparations without added antibody has revealed distinct morphological differences and viruses previously thought to be simply antigenic variants within the Norwalk group of viruses clearly belong to other groups. Preliminary evidence suggests that one human virus unrelated to Norwalk has a single-stranded DNA genome and is a parvovirus. Some groups have been implicated in outbreaks of food-borne gastroenteritis, particularly after the consumption of shellfish, and their role in other food-borne and water-borne outbreaks is being increasingly recognized.

Caliciviridae↗
PubMed1975

Serologic classification of scrub typhus isolates from Pakistan.

Detailed serologic characterization of 79 isolates of Rickettsia tsutsugamushi from Pakistan was performed by using complement fixation and direct immunofluorescence techniques for comparison with three prototype strains. Seventy-one were of the Karp serotype and one was of a Gilliam serotype. Seven isolates were multiply-reactive: one with Karp and Gilliam, 3 with Karp and Kato, and 3 with Karp, Gilliam and Kato, No strain failed to react with at least 1 of the 3 prototype antisera. No correlation of antigenic types with local geographic factors, animal hosts, vecotr mites, or specific strain virulence was observed. These findings suggest the possibility that antigenic heterogeneity may be more restricted in areas peripheral to the geographic epicenter of scrub typhus endemicity, that the serotypes are relatively stable genetically and that new geographic variants are probably infrequent. The importance of these findings to the practical problems of immunoprophylaxis and serodiagnosis are discussed.

Animals↗
PubMed2005

Immunohistochemical appearance of HNE-protein conjugates in human astrocytomas.

Gliomas are tumors originating from astrocytes, oligodendrocytes or ependimal cells. Those of astrocytic origin are the most widespread of primary brain tumors and account for more then 60% of all CNS neoplasms. The current state of knowledge on the associations between tumor etiology and oxidative stress suggests that environmental factors that cause oxidative stress could also induce and promote cancer, especially in case of hereditary predisposition. Among mediators of oxidative stress, lipid peroxidation product 4-hydroxynonenal (HNE) is of particular relevance in oncology, as it is known to act as a growth-regulating factor and a signaling molecule. The aim of present study was to investigate by immunohistochemistry the presence of HNE-modified proteins in different types of astrocytoma. Our study comprised 45 astrocytic tumors. These tumors were graded in accordance with the WHO classification as diffuse astrocytomas (DA), anaplastic astrocytomas (AA) and glioblastomas (GB), while each group comprised 15 tumors. Slides of paraffin-embedded tumor tissue were stained with hematoxylin-eosin or were prepared for immunohistochemistry with monoclonal antibodies to HNE-histidine conjugate. Positive immunohistochemical reaction to HNE was analyzed semi-quantitatively. HNE positivity was proportional with malignancy of astrocytomas. The weakest presence of HNE-histidine adducts was found in DA, followed by AA and GB. Lowest intensity of HNE immunopositivity was present in tumor cells of almost all DA, predominantly around blood vessels. In malignant variants of astrocytoma, AA and GB, HNE positivity was moderate to strong, and diffusely distributed in all tumors.

Aldehydes↗
PubMed2005

[Malignant fibrous histiocytoma: pleomorphic sarcoma NOS or pleomorphic fibrosarcoma].

The entity and nosology of pleomorphic malignant fibrous histiocytoma (MFH) is still ambiguous. The actual WHO-Classification uses pleomorphic malignant fibrous histiocytoma (MFH) and pleomorphic sarcoma NOS (not otherwise specified) synonymously. On the other hand text and illustrations convey the impression, that these tumors also could be pleomorphic lipo-, leio- or rhabdomyosarcomas etc. It would have been more informative to emphasize, that with the above mentioned specific sarcoma types MFH-like appearance may occur. Furthermore it would have been more up to date to consider pleomorphic sarcomas NOS as pleomorphic fibrosarcomas and include them in the chapter of fibroblastic and myofibroblastic tumors. This concept already has been carried out for the former myxoid variant of MFH, nowadays preferentially called myxofibrosarcoma. There is controversial discussion about the clinical significance of exact typing of pleomorphic sarcomas. Problems may also occur due to the lack of standards, which degree of desmin expression signifies leiomyosarcoma or just indicates myofibroblasts in MFH. The requirement of exclusion of other tumor-types before diagnosing pleomorphic fibrosarcoma still remains obligatory. After verification of the diagnosis pleomorphic sarcoma NOS or pleomorphic fibrosarcoma, grading e.g. according to criteria of the FFCCS can be carried out. Most cases of pleomorphic fibrosarcoma will qualify as high grade malignant.

Diagnosis, Differential↗
PubMed1996

Mantle-cell lymphoma: classification and therapeutic implications.

Mantle-cell lymphomas have been recognized in the new Revised European-American Lymphoma Classification as a peripheral B-cell neoplasm that has a distinct morphologic, immunologic, and genetic phenotype. Mantle-cell lymphomas have been subtyped into four categories, termed 'mantle zone', 'nodular', 'diffuse', or 'blastoid'. The incidence of the 'mantle-zone' pattern remains controversial. The fact that patients with the nodular, diffuse, or blastoid subtypes of mantle-cell lymphoma have a high proliferative rate resulting from overexpression of the cyclin D1 and a very short median survival demonstrates conclusively that these patients should be categorized as having an aggressive lymphoma. Most authorities believe that the 'mantle zone' variant pursues a more benign clinical course than the other subtypes. Trials of the new purine analogs are of great interest in these mantle-zone lymphoma patients.

Antineoplastic Agents↗
PubMed1992

Diversity of immunodominant 56-kDa type-specific antigen (TSA) of Rickettsia tsutsugamushi. Sequence and comparative analyses of the genes encoding TSA homologues from four antigenic variants.

There are several antigenic variants in Rickettsia tsutsugamushi, and a type-specific antigen (TSA) of 56-kilodaltons located on the rickettsial surface is responsible for the variation. The primary structures of the protein in two variants, Gilliam and Karp, have been reported independently by us and Stover et al. by cloning and sequencing the corresponding genes (Ohashi, N., Nashimoto, H., Ikeda, H., and Tamura, A. (1990) Gene (Amst.) 91, 119-122; Stover, C. K., Marana, D. P., Carter, J. M., Roe, B. A., Mardis, E., and Oaks, E. V. (1990) Infect. Immun. 58, 2076-2084). In the present study, genes encoding the TSA homologues of the other four variants, Kato, Kawasaki, Kuroki, and Shimokoshi, which are all distinguishable serologically, were cloned and sequenced, and consequently, it became possible to compare the primary structures of the six antigenic variants. The sequence analyses revealed a complete open reading frame encoding 55,308-56,745-dalton proteins with 521-532 amino acids, in which a putative signal peptide consisting of 22 amino acids was recognized at the NH2-terminal end. Transcription of the gene is regulated by several tandem promoters. All TSA molecules have the characteristics of transmembrane proteins with alternating hydrophobic and hydrophilic regions, and contain four variable domains with spans of 16-40 amino acids which are located in the hydrophilic regions in the molecule and show different amino acid sequences among the strains. Phylogenetic classification among the R. tsutsugamushi strains based on TSA homologues supports the antigenic relationships known in the closely and distantly related strains.

Amino Acid Sequence↗

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