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Alternative splicing of CD44 pre-mRNA in human colorectal tumors.

Expression of the CD44 molecule has been linked to tumor growth and metastases in both human and rodent cancers. Alternatively spliced variants expressed in rat and mouse tumors have been shown to confer metastatic potential to non-metastatic carcinoma cell lines, and human homologues of rat variant mRNA sequences are expressed in human tumors. In the present study matched sets of RNA from adenocarcinomas of the colon and distant normal mucosa were assayed for CD44 expression by quantitative RT-PCR. Retrospective analysis revealed that colonic tumor cells had both quantitative and qualitative differences in CD44 expression when compared to normal mucosa. These were: 1) an increase in levels of CD44 transcripts, 2) an increase in levels of alternatively spliced transcripts, 3) the presence of larger alternatively spliced transcripts with inserts > 400 bases and 4) the primary alternatively spliced CD44 isoform in colonic adenocarcinomas in all cases is CD44R. Interestingly, two patterns of CD44 isoform expression termed "variant dominant" or "balanced" patterns of expression, based on the ratio of variant to standard CD44 transcripts (R+V's/H), could be differentiated. An unfavorable prognosis was suggested for tumors expressing increased levels of CD44 variant exons previously associated with tumor metastasis. Specifically, patients with tumors expressing the "variant dominant" pattern of expression irregardless of Dukes classification and Dukes C and D staged tumors of both patterns exhibited a poorer prognosis.

Adenocarcinoma

Ocular palsy preceding chronic relapsing idiopathic polyneuropathy. Poor response to plasma exchange.

We report a case of chronic relapsing idiopathic polyneuropathy developing six weeks after the onset of extraocular palsy. As in the other four published cases, the patient failed to respond to steroids and also in this case to plasma exchange, thus confirming the poor prognosis. The electrophysiological features and poor response to plasma exchange are at variance with a demyelinating pathogenesis and suggest classification of this form as a distinct clinical variant.

Adult

Phylogeny of Serpulina based on sequence analyses of the 16S rRNA gene and comparison with a scheme involving biochemical classification.

Twenty-one putative Serpulina strains, representing six proposed biochemical groups, were selected for phylogenetic studies based on 16S rRNA sequencing. The biochemical groups were distinguished by the degree of beta-haemolysis, indole production, hippurate hydrolysis and alpha-galactosidase-, and beta-glucosidase activity. The 16S rRNA sequences of the U2 to U5 region, including three evolutionarily variable regions, from representatives of each biochemical group were determined by automated solid phase DNA sequencing after in vitro amplification by the polymerase chain reaction (PCR). The sequences generated were 532 nucleotides in length. Sequence alignments showed that all the strains were closely related, with six informative positions in the region sequenced. A dendrogram was constructed from these data and compared with the tentative biochemical classification. The results support the proposed biochemical classification and indicate that at least five genetic variants of the genus Serpulina can be identified.

Animals

The immunologic approach to analysis of malignant lymphoma. Mantle zone lymphoma of the ileocecal region.

We studied an unusual type of lymphoma of the ileocecal region using an established protocol that combines morphologic, flow cytometric, and immunohistochemical analyses. This lymphoma grew as multiple submucosal nodules, some of which had coalesced into a mass in the terminal ileum. Histologically, the lesion resembled a lymphoma of follicular center-cell origin except for germinal centers that appeared reactive and greatly expanded follicular mantles. Flow cytometric studies showed that the lymphoma contained a monoclonal, kappa+ population of B-lymphocytes. Evaluation of sections of frozen tissue by an immunoperoxidase technique revealed that the germinal centers were polyclonal (nonneoplastic) and that the neoplastic cells were confined to the mantle zone. The additional information led to classification of the neoplasm as the mantle zone variant of intermediate lymphocytic lymphoma. This type of lymphoma may pursue a more aggressive course than a follicular lymphoma derived from the germinal center. We review our general approach to the analysis of hematolymphoid neoplasms and discuss how certain techniques may be useful adjuncts in the evaluation of these types of tumors.

Antibodies, Monoclonal

Root length, crown height, and root morphology in Turner syndrome.

Root length, crown height, and root morphology were studied on intraoral and panoramic radiographs in 33 Turner syndrome patients aged 7.0-16.7 years, subdivided on the basis of karyotype. Thirty-three normal girls aged 10.2-16.4 years served as controls. In the 45X patients and, with the exception of a few teeth, also in the isochromosome and mosaic karyotypes, root length and crown height of incisors, canines, and premolars were significantly reduced. Some teeth showed altered crown-root proportions. Maxillary first premolars showed a significantly increased number of two-rooted and three-rooted variants. Mandibular premolars and molars had a complex root morphology, and a classification system was established including four premolar and six molar root types. Premolars had a significantly increased number of root components. Some of the variants, such as a molar-like second premolar, are apparently specific for these patients. On several first molars a radix entomolaris was identified. Two separate mesial and one or two separate distal roots were also frequently seen. Our investigation demonstrates that X-chromosome deficiency influences root formation.

Adolescent

[Consensus 'diagnosis of short stature in children.' National Organization for Quality Assurance in Hospitals].

Each year about 2500 children in the Netherlands are referred to a specialist because of short stature. Aim of the consensus meeting: 'Diagnosis of short stature in childhood' by general practitioners, pediatricians and pediatric endocrinologists was to promote early diagnosis and treatment of aberrant growth but also to prevent unnecessary referral and interventions. For optimal treatment of growth disorders early diagnosis is of the utmost importance. Short stature is best detected by the use of standard deviation scores (SDS) instead of percentile lines. As cut-off point for referral SDS < -1.3 (< P10) was chosen in order to identify risk groups that need further evaluation. Based on international consensus a diagnostic classification of short stature is possible, distinguishing normal variants and (or) idiopathic short stature from primary and secondary growth disorders. Using target length, the growth curve in the SDS diagram, the actual age and puberty signs, the general practitioner can use a flow chart to determine whether there is a growth problem and whether this needs treatment in primary or secondary health care. Measuring skeletal age has no additional value. Attention should also be given to psychosocial problems as the cause or the effect of short stature.

Adolescent

Major retroperitoneal venous anomalies: surgical considerations.

Nineteen major anomalies of the vena cava or its branches were encountered in patients requiring abdominal vascular surgery and related procedures at Barnes Hospital during the past 5 years. The classification of these anomalies, their embryologic development, associated variants, and surgical considerations are discussed. Careful review of preoperative computed tomographic scans and familiarity with these anatomic variants may allow the surgeon effectively to avoid potentially disastrous intraoperative consequences.

Humans

[Nephroblastomas (Wilms' tumors) and special variations of nephroblastomas].

The results of the National Wilms' Tumor Study (NWTS) enabled the subdivision of nephroblastomas into subtypes with "favorable and unfavorable histology". Nephroblastomas with "unfavorable histology" could be discriminated by identifying those tumors not responding to therapeutic regimes proven successful for most cases with "favorable histology". A major disadvantage of the NWTS classification has been the exclusion of cytodifferentiated nephroblastoma variants, which, in contrast to typical nephroblastomas, can be cured by complete nephrectomy with wide excision of perinephric soft tissue. In the current study all types of nephroblastoma and nephroblastoma variants were included to encompass the whole morphological spectrum which these tumors may assume. This unselected material is necessary to define the relation between morphology and prognosis and to compare the treatment results of various clinical trials. Three hundred and four cases of nephroblastoma and related neoplasms on file at the Pediatric Tumor Registry, Kiel, were investigated by conventional light microscopy, electron microscopy, immunohistochemistry and DNA-flow cytometry. Of the "typical" nephroblastomas 50% occurred in the left kidney, 45% in the right kidney, and 5% were bilateral. Five cases were located in extrarenal sites. There were 121 males and 114 females. The peak incidence was noted in the third year of life. Of 135 patients 111 are alive and well, nine are living with disease, and 10 patients have died of disease. The blastemal predominant and stromal predominant types in our study were more frequent than in the NWTS. By contrast, the mixed and epithelial predominant types were more frequent in the NWTS. Patients with nephroblastomas of mixed or blastemal predominant type were older than those with epithelial predominant or stromal predominant type. Electron microscopy showed that nephroblastoma is derived from metanephric blastema. Blastemal cells are capable of differentiating into tubular epithelial cells and stromal cells. Undifferentiated blastemal cells contain exclusively vimentin intermediate filaments, better differentiated blastemal cells vimentin and cytokeratin, and stromal cells exclusively vimentin. Preoperative radio- and/or chemotherapy led to a marked reduction of undifferentiated blastema and poorly differentiated tubules, whereas better differentiated tubules, striated muscle, hyaline cartilage, cells with anaplastic and sarcomatous elements were not affected. Thus, identification of highly malignant nephroblastomas with anaplasia and sarcomatous renal tumors was even possible after preoperative treatment. Congenital mesoblastic nephroma (CMN; n = 17) is a low-grade malignant, cytodifferentiated nephroblastoma which very rarely occurs beyond the fourth month of life and has an excellent prognosis, provided it has been completely resected.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent

Prognostic implications of blast cell morphology in childhood acute lymphoblastic leukemia: a report from the Childrens Cancer Study Group.

The Childrens Cancer Study Group (CCSG) has evaluated French-American-British (FAB) morphology in newly diagnosed children with acute lymphoblastic leukemia (ALL) since 1975. A modification of the FAB system was used in which individual lymphoblast cells were scored and designated as either L1 or L2 on the basis of distinctive morphologic characteristics. L1 ALL was defined as less than 10% L2 cells and greater than 90% L1 cells; L2 ALL was defined as greater than or equal to 10% L2 cells and less than 90% L1 cells. FAB morphology was an independent predictor of overall survival (P = 0.02) in CCSG-141 and a highly significant predictor of successful induction of complete remission and event-free survival in the CCSG-160 series (P = 0.00001). These studies involved nearly 3900 patients. Two concordance studies have been performed. In the first (1981) study, overall concordance between the FAB reference laboratory and member institutions was 76% using a two-category system (L1, non-L1), 86% for L1 cases, and 47% for non-L1 cases. In the second (1984) concordance study, the use of more stringent, semiquantitative definitions of L1 and L2 lymphoblasts did not improve overall (75%), L1 (89%), or non-L1 (46%) concordance. The results of reference laboratory classification more powerfully predicted event-free survival than did member institutions (P = 0.016 vs P = 0.125). Quality control factors (slide preparation, cellularity, staining quality, and discipline of the reviewer) did not influence concordance. These results justify the continued assignment of patients to protocols of the CCSG-100 series on the basis of the modified FAB classification. The biological significance of the FAB morphologic variants remains to be determined.

Child

[Clinico-morphological characteristics and working classification of kidney diseases in patients with systemic scleroderma].

Based on a study of 110 patients with systemic scleroderma (SSD) (74 had involved and 36 uninvolved kidneys) the authors provide the clinico-functional and morphological characteristics of renal lesions and the working classification of sclerodermic nephropathy (SN). The two basic variants of SN were recognized: acute and chronic. The latter one was subdivided into clinical, moderate and pronounced SN. A correlation was revealed between the functional (glomerular filtration lowering) and ultrastructural (reticulation of endotheliocytes and thickening of the basal membrane of the glomerular capillaries) signs evidencing derangement of the microcirculatory bed. Morphological examination of the kidneys disclosed alterations that mirror the complex pathogenesis of SSD: derangement of the microcirculatory bed, immunopathological disorders, activation of connective tissue components.

Adolescent

[Carcinoma of the major duodenal papilla].

The analysis of 134 postmortem cases and 65 clinical observations of carcinoma of the major duodenal papilla (MDP) has revealed different variants of development of carcinoma of MDP. The classification by the TNM system is made. In 34% of cases carcinoma was found to spread beyond the duodenum limit. Papillectomy should not be considered radical intervention. Average survival time after papillectomy was 17 months, after pancreatoduodenal resection it was 34 months. Fibroduodenoscopy, laparoscopic cholecystocholangiography in combination with relaxation duodenography was used for early diagnosis of carcinoma of MDP. Laparoscopic investigation was always accomplished by laparoscopic cholecystostomy which permitted avoiding hepatic insufficiency in the postoperative period.

Adult

[The dependence of the progression of chronic glomerulonephritis on the clinical and morphological types of glomerulonephritis and on the tubulointerstitial changes].

Progression of chronic glomerulonephritis (CGN) is strongly associated with morphologic type of the disease, tubulointerstitial changes, some clinical syndromes. The aim of the study was to trace relations between the onset of chronic renal failure within 7 years since the diagnosis (fast progression of CGN--FP CGN), CGN clinical variant according to M. Ia. Ratner et al. classification (1987) and histomorphological changes in the renal biopsy. Unfavorable clinical types (active nephritic types and nephrotic-hypertensive type) proved dominating predictor of FP CGN not only because of close relationship between these type and FP CGN but also due to FP CGN occurrence in morphologically unfavorable morphological types and tubulointerstitial changes in line with concomitant unfavorable clinical types.

Adolescent

[Classification of the types of blood supply of the muscles from the standpoint of plastic surgery].

Based on an experience with 120 composite flaps including the muscle and with special account of literature data the author describes a new classification of types of blood supply of muscles. The author proposes 6 types of blood supply of muscles and substantiates a direct relationship between the anatomy of muscle vessels and variants of its use for plasty. A comparison of the new classification and other classifications was made.

Blood Vessels

[The importance of the clinical classification of chronic glomerulonephritis for the prognosis of its progression and of the efficacy of therapy].

A significant correlation exists between clinical types of chronic glomerulonephritis (CGN) in a new clinical classification and morphological CGN types according to classification of WHO experts. Rapid progression is significantly correlated with clinicomorphological variants of CGN represented by unfavorable clinical types and unfavorable morphological types. No rapid progression occurred in combination of clinically favourable types and morphologically favourable and unfavorable types. The above classification is recommended for practice.

Adolescent

[Effects of immunologic markers on prognosis in acute lymphoblastic leukemia in young children].

Altogether 77 children aged up to 3 years with acute lymphoblastic leukemia (ALL) were examined for the immunological phenotype of blast cells. L1, L1/L2, L2/L1, L2 variants of ALL and the undifferentiated one were established in accordance with criteria of the FAB classification. T1, zero and Ia immunosubvariants were recorded most frequently. Mature cell T2 and pre-B variants (3 and 2 cases, respectively) were rare; B-cellular acute lymphoblastic leukemia was lacking; the "common" subvariant was revealed in 28 patients. The patients' age produced the highest effect on the prognosis: the significantly least disease standing and remissions were noted in a group of children under 2 years as compared to those aged 2 to 3 years. As for immunological markers, expression of Thy1-antigen exerted an unfavourable effect on the prognosis and duration of the first remission.

Antibodies, Monoclonal

Classification and survival rate of patients with serous cystadenocarcinoma of the ovaries.

The comparative evaluation of two stage classifications including USSR Ministry of Health stage classification and TNM system was performed on the base of studies of the end results of 419 patients with serous cystadenocarcinoma of the ovaries. It has been established that TNM system is of a greater importance in establishing more accurate prognosis than the stage classification of the Ministry of Health. In TNM system four variants of the degree of extension correspond to each stage that allows to evaluate not only the extent of the primary tumor that also of the metastatic spread. The achieved results point to the superiority of the TNM system and serve as a base for transition to the TNM system in the classification of ovarian carcinoma.

Cystadenocarcinoma

Hürthle cell (oxyphilic) papillary thyroid carcinoma: a variant with more aggressive biologic behavior.

The latest World Health Organization International Classification defines papillary thyroid carcinoma by its "follicular cell differentiation...as well as characteristic nuclear changes". However the oxyphilic (Hürthle cell) papillary carcinoma have nuclei which generally resemble the nuclei seen in oxyphilic follicular carcinomas, and such oxyphilic papillary tumors may behave more aggressively than typical papillary cancers. To further characterize these rare tumors, we identified during a 32-year period 22 patients with oxyphilic papillary cancer and compared them with 1,084 patients with typical papillary cancers and 57 patients with oxyphilic follicular cancers treated by the Mayo surgical group during the same time period. Although typical papillary and oxyphilic papillary cancers were comparable with regards to patient age, tumor size and extent, TNM stage, and prognostic score (AGES), there were significant differences. Compared to typical papillary tumors, oxyphilic papillary cancers had fewer neck nodal metastases at primary diagnosis (5% vs 40%, p less than 0.0001), were more often DNA non-diploid (71% vs 21%, p less than 0.001), and after 10 postoperative years had higher rates of both tumor recurrence (28% vs 11%, p less than 0.0001) and cause-specific mortality (1.7% vs 4%, p less than 0.0005). In these four important respects the oxyphilic papillary cancers more resembled the oxyphilic follicular cancers. For oxyphilic follicular cancers, the frequency of initial neck nodal metastases was 7% (cf 5%); 83% of the oxyphilic follicular tumors were non-diploid (cf 71%), and at 10 years postoperatively the tumor recurrence and cause-specific mortality rates were 28% and 18%, insignificantly different from 28% and 17% seen with the oxyphilic papillary cancers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Pyoderma gangrenosum: classification and management.

Pyoderma gangrenosum (PG) has four distinctive clinical and histologic variants. Some have morphologic and histologic overlapping features with other reactive neutrophilic skin conditions. PG often occurs in association with a systemic disease, and the specific clinical features of the skin lesion may provide a clue to the associated disease. Management of PG depends on its type and severity and usually requires aggressive local and systemic treatment.

Humans