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PubMed1999

Carcinoma of the uterine cervix: a review of its pathology and commentary on the problem in Malaysians.

Since its recognition about 150 years ago, there has been much progress in the understanding of the pathogenesis, prevention, early detection and management of carcinoma of the uterine cervix. Important historical landmarks include the (1) recognition of pre-invasive and pre-clinical lesions, and the devise of various systems for reporting these lesions, (2) improvements in diagnostic techniques particularly colposcopy, (3) advent of therapeutic procedures (electrocoagulation, cryotherapy, laser therapy and loop electrosurgical excision), and (4) recognition of the aetiological relationship between the human papillomavirus and cervical neoplasia. The susceptibility of the cervical transformation zone to malignant change is now well recognised. The WHO classification system remains the one most commonly utilised for histological reporting of cervical cancers. In the recent 1994 update, cervical carcinoma is divided into 3 main categories: squamous cell carcinoma, adenocarcinoma and other epithelial tumours. Squamous cell carcinoma (60-80%) predominates among invasive cervical carcinoma. Recognised variants include verrucous, warty (condylomatous), papillary squamous (transitional) and lymphoepithelioma-like carcinoma. Adenocarcinoma (5-15% of invasive carcinomas) shows an increasing trend in young females. Like its squamous counterpart, preinvasive and microinvasive versions are known. Variants such as mucinous, endometrioid, clear cell, mesonephric, serous, villoglandular and minimal deviation carcinoma are now defined. Adenosquamous carcinoma (5-25%), adenoid-cystic, adenoid-basal, neuroendocrine and undifferentiated carcinomas constitute other epithelial tumours of the cervix. The management of invasive cervical carcinoma remains heavily dependent on its stage. The FIGO staging system remains the most widely used. The 1995 update provides more definite criteria in subdividing stage IA tumours by delimiting stromal invasion of stage IA1 lesions to a maximum depth of 3 mm and a horizontal axis of 7 mm. In Malaysia, an appreciation of the cervical carcinoma problem has to take into consideration the population at risk, its multi-ethnicity, its socio-economic and geographical diversities and the constraints of the health care system. Females form 48.9% of the Malaysian population. 52.9% of them are in the sexually active age group of 15-50 years, indicating a significant population at risk for cervical carcinoma. Cervical carcinoma was the third most common cause of death due to solid tumours among Malaysian females in 1995 following carcinoma of the breast and respiratory tract. East Malaysia is predominantly rural with many communities having limited modern facilities. Such areas imply a lower educational and socio-economic status, raising the worry of a population at higher risk for developing cervical carcinoma. The population: doctor for Malaysia of 2153:1 compares poorly with nearby Singapore. Besides a shortage of doctors, there is also an uneven distribution of doctors, resulting in a ratio in East Malaysia of > 4000:1. Although Malaysia does not have a national cervical cancer-screening programme, many action plans and cancer awareness campaigns have been launched throughout the years, which appear to have made an impact as evidenced by the decreasing mortality rates from cervical carcinoma. Another interesting feature of cervical carcinoma in Malaysia relates to its multiethnic population. In Malaysian Chinese and Malay females, the prevalence of cervical carcinoma ranks second to breast cancer whereas the pattern is reversed in Malaysian Indian females. Studies into its aetiology and pathogenesis are being undertaken and may shed more light on this matter.

Carcinoma↗
PubMed2002

Genetic polymorphisms of the interleukin-4 receptor alpha gene are associated with an increasing risk and a poor prognosis of sporadic renal cell carcinoma in a Japanese population.

PURPOSE: It has been suggested that the immune system of the host may be capable of modulating the clinical course of renal cell carcinoma (RCC) patients. In fact, the amount of Th2 cytokines such as interleukin (IL)-4 and IL-10 in the serum of patients has been found to be an important predictor of poor prognosis. Recently, it was reported that genetic polymorphisms of the IL-4 receptor alpha (IL-4Ralpha) gene affect the strength of signaling through the receptor. In addition, these same polymorphisms were found to be associated with an increased risk of atopy by causing Th2-dominated responses of the host. The significance of the polymorphisms on the incidence and prognosis in sporadic RCC patients were examined to clarify the role of IL-4 as well as that of the Th1/Th2 immune system in this disease. EXPERIMENTAL DESIGN: A case-control study was performed with 143 sporadic RCCs in a Japanese population and 205 Japanese controls. Logistic regression models were also used to assess the genetic effects on prognosis. RESULTS: The frequencies of variant alleles that enhance signaling of IL-4 were significantly related to an increased risk of RCC. Furthermore, multivariate regression analysis showed that the genotype of the IL-4R gene was an independent prognostic factor for cause-specific survival (P = 0.018) together with M classification (P = 0.0002) and histopathological grade (P = 0.044). CONCLUSIONS: The present findings show that the preferential Th2-type response to tumors was associated with a poorer prognosis and suggest that polymorphisms of the IL-4Ralpha gene may serve as useful genetic markers for assessing the risk of the development and progression of RCC.

Adult↗
PubMed2006

Down-regulation of MLL-AF9, MLL and MYC expression is not obligatory for monocyte-macrophage maturation in AML-M5 cell lines carrying t(9;11)(p22;q23).

The MLL-AF9 oncogene originates from the translocation t(9;11)(p22;q23), which is mainly associated with monocytic acute myeloid leukaemia (AML-M5; FAB-classification). In AML-M5 THP-1 cells carrying t(9;11) (p22;q23) and expressing MLL-AF9, we previously showed that MLL-AF9 expression is down-regulated during monocyte-macrophage maturation. We have subsequently observed that in a 'rapid-growing' variant of the THP-1 cell line (THP-1-R) MLL-AF9 down-regulation does not occur. MLL fusion proteins (including MLL-AF9) deregulate MYC transactivation activity, and both presence and absence of MYC down-regulation have been reported during monocyte-macrophage maturation in THP-1 cells. In the present study, we analyze the expression patterns of MLL-AF9, MLL wild-type and MYC after induction of monocyte-macrophage terminal differentiation in the AML-M5 cell lines, THP-1, THP-1-R, Mono-Mac-6 (MM6) and MOLM-13, all of which carry t(9;11)(p22;q23) and express MLL-AF9. RT-PCR analysis indicated that down-regulation of MLL-AF9, MLL or MYC is not necessary to abolish malignant phenotypes by induction of terminal monocyte-macrophage differentiation in leukaemic cells carrying t(9;11)(p22;q23).

Cell Differentiation↗
PubMed1986

Correlation of surface marker expression with morphologically and immunologically defined subclasses of acute myeloid leukaemias.

The expression of myeloid-associated cell surface antigens detected by monoclonal antibodies (MoAb: MCS-2, MCS-1, MY7, MY9, Leu-M1, OKM1, VIM-D5, Mol, My-1, MY8, MY4, Leu-M3, VIM-D2, Mo2) of the HLA-DR/Ia-like antigen and of the Fc-receptor was determined on the blast cells from 91 patients with acute myeloid leukaemias classified as M1-M5 in the French-American-British (FAB) system. The surface antigen analysis revealed a highly heterogeneous reaction profile. Nevertheless, distinctive patterns of marker expression referring to morphologically defined subgroups were delineated. Several MoAb (especially MCS-2 and MY7 which were positive in most cases of the five FAB subgroups) appear to be useful for the recognition of myelomonocytic cells regardless of the commitment to either the granulocytic or monocytic cell lineage whereas other Mo Ab (especially MY4, Leu-M3, VIM-D2, Mo2) react predominantly with the monocytic variants and are helpful in the identification of monocytic commitment. The 91 cases could be divided into three immunologically defined phenotypes (Types I-III) corresponding to sequential differentiation levels. Correlations of these MoAb-defined phenotypes with the FAB subtyping showed that immunological and morphological classifications are not completely concordant and that only the parameters Type I and FAB M1 were significantly related. A scheme of early myeloid differentiation sequences based on the expression of surface antigens is presented.

Adult↗
PubMed1989

[Classification, histogenesis, and prognosis of renal cell carcinoma and renal oncocytoma].

Typing of renal cell tumours according to cytomorphological criteria results in different basic cell types, i.e. the clear cell type, the chromophilic cell type, the chromophobic cell type, the oncocytic cell type and the cell type of Duct-Bellini-Carcinoma. Each basic cell type exhibits a typical spectrum of cytological variability including eosinophilic (granular) variants. Antigenic properties of the proximal tubule can mainly be detected in clear cell and chromophilic renal cell carcinomas, whereas antigenic properties of the connecting tubule and collecting duct can be found especially in the chromophobic renal cell carcinoma and oncocytoma as far as in Duct-Bellini-Carcinoma. These different phenotypes of epithelial renal cell tumours are possibly due to various histogenetic pathways. Prognostic factors in renal cell carcinoma include staging, grading and to a less extent cytological and histological parameters which are summarized in a new prognostic score. From this score, three significantly distinct prognostic groups evolved with a correct prognosis of over 80% on the average for an individual case, which suggests a great prognostic potential.

Adenoma↗
PubMed1984

[Morphometric analysis of the dorsal lateral geniculate body of the laboratory mouse and microphthalmic variants].

The dorsal lateral geniculate nucleus (dLGN) of the mouse (strain 944 with microphthalmus syndrome, P. Hertwig 1942) has been morphometrically investigated. The eyes of the gray littermates develop normally (control animals) while the white littermates show the microphthalmus syndrome (microphthalmic animals). Four male twentyone day old animals were examined. Following perfusion with formaldehyde (diluted 1:4 with H2O) Nissl stained frontal sections were used for classification of neurons. we differentiate between projection neurons (PN) (geniculo-cortical relay neurons) and interneurons (IN). We succeeded in identifying these two cell types using deimpregnated Golgi preparations (Fairén et al. 1977), which were counterstained with methylene blue (0.1%). The neuronal packing density and the ratio PN:IN were conventionally determined using 20 micron thick sections from both control and microphthalmic animals. In both cases this ratio was 12:1 (= 8% IN). Measuring fields distributed in a meander-like manner were selected for estimating the neuronal density. Measuring fields giving equal values were connected. The results show that we can distinguish between 3 regions of dLGN: lateral, medial and caudal. They differ with regard to neuronal packing density, size and structure of the PN. Using 3 micron thick Nissl stained sections from both control and microphthalmic animals the size and structure of PN were automatically determined using the picture processing device "MORPHOQUANT" VEB Carl Zeiss JENA). The distribution pattern of IN is apparently uniform. The microphthalmus syndrome produces a diminished number of pathologically changed retinal fibers. The morphometrically registered findings show that within the dLGN, of the microphthalmus mouse the neuronal packing density increased (diminution of neuropil), the size of PN decreased and their structural density increased (transneuronal dystrophy). Compared with the other parts, the medial part of the dLGN is minimally altered.

Animals↗
PubMed1994

Phylogenetic classification of human T cell leukaemia/lymphoma virus type I genotypes in five major molecular and geographical subtypes.

Proviral DNA was obtained from ex vivo peripheral blood mononuclear cells of 75 human T cell leukaemia/lymphoma virus type I (HTLV-I)-infected individuals who were either asymptomatic or had adult T cell leukaemia or tropical spastic paraparesis/HTLV-I-associated myelopathy. Amplified long terminal repeats (LTRs) were analysed for restriction fragment length polymorphisms (RFLPs). The results, together with previously published LTR data (a total of 180 specimens analysed), showed the presence of 12 different RFLP profiles with four major molecular subtypes. Furthermore, a fragment of 413 bp (nucleotides 22 to 434) of the U3/R region was sequenced for 12 new HTLV-I specimens originating from Central and West Africa (8 cases), Iran (1 case), Caribbean (2 cases) and Reunion Island (1 case). Phylogenetic analysis using three different techniques (maximum parsimony, neighbour-joining and UPGMA) comparing these 12 strains (including four new African HTLV-I variants) with the 30 published partial HTLV-I LTR sequences (nt 120 to 434) showed the existence of clusters of molecular variants in discrete geographical areas. The topology of the phylogenetic trees is thought to reflect HTLV-I evolution and the migrations of virally infected populations in the recent or distant past. Furthermore, there was a nearly perfect concordance between the clustering based on the LTR sequence homologies and the LTR RFLP subtypes suggesting that this rapid and simple technique is well suited to the investigation of HTLV-I molecular epidemiology. These results allow a new phylogenetic classification of HTLV-I genotypes into five major molecular subtypes: Cosmopolitan (C) subtype widespread all over the world, Japanese (J) subtype, West African (WA) subtype. Central African (CA) subtype and Melanesian (M) subtype.

Africa↗
PubMed1995

Vertical facet splitting: a special variant of rotary dislocations of the cervical spine.

A special variant of rotary displacement of the cervical spine with vertical splitting of an inferior articular process by its articulating partner is reviewed. Eighteen patients with unilaterally locked facet joints confirmed by computerized tomography were seen between 1986 and 1991. Five patients presented with vertical split fractures of an inferior articular process by impaction of the superior process of the subjacent vertebra. This specific fracture pattern is not accounted for in current classifications. Four males and one female with a mean age of 31 years (range 16 to 49 years) were affected. Three of the patients showed no neurological deficits. One patient presented with cerebral contusion and paresis of the right upper extremity, and in one patient the posterior funiculus was involved. Three of the injuries had been sustained recently; the other two were of longer duration. Surgical treatment was chosen in the three cases of recent injury. In two cases surgery was prompted by neurological deficits; in the third case impaction was felt to be of inadequate depth. Surgery consisted in fracture reduction and interbody fusion using plates. The two cases of long-term fractures were treated conservatively, and ankylosis of the facet joints eventually provided adequate stability. If radicular or spinal symptoms are absent, this special variant of locked facet joints can successfully be treated conservatively leaving the rotary displacement uncorrected, provided impaction is adequately deep. The author's experience has shown that indications for surgical management are relative rather than absolute in this fracture variant and that use of computerized tomography is essential to establish the fracture pattern.

Adolescent↗
PubMed2004

Advances in the diagnosis and classification of chronic lymphoproliferative disorders.

In this review, we have highlighted recent advances in chronic lymphoproliferative disorders that commonly involve the peripheral blood. As we have seen, our concepts of certain diseases are changing. Molecular genetic and immunophenotypic studies are allowing more precise characterization of CLL and defining important biologic markers that predict clinical behavior. Prolymphocytic leukemia is now more narrowly defined and its relationship to nucleolated variants of MCL is now apparent. With new reagents and techniques applied to problems such as identification of Sezary cells and T-cell monoclonality determination, our ability to diagnose, monitor, and provide prognostic information is improving. Insight into the biology of these diseases also may provide new therapeutic targets in the future.

Chronic Disease↗
PubMed1977

[Classification of lymphogranulomatosis].

Histological and cytological studies of preparations of peripheral lymphatic nodes in 1081 patients before treatment were carried out. In 76 patients there were also investigated morphological changes in the spleen, mesenteric lymphatic nodes and parts of the liver obtained in laparotomy. Basing on the analysis of the literature and their own findings, the authors think it reasonable to single out the following 8 histological variants of untreated lymphogranulomatosis: focal lesion; a group of variants with nodular sclerosis, with various cellular composition--lymphocytic predominance, mixed cellularity, predominance of lacunar cells; a group of variants without sclerosis consisting of lymphoid predominance and mixed cellular variant; a group of lymphatic depletion combining the reticular variant and diffuse fibrosis. The variants indicated above may be both independent and transitional stages.

Hodgkin Disease↗
PubMed1999

[Metaplastic meningioma with cartilaginous differentiation].

A meningioma with cartilaginous areas is described. The tumour arose in the region of the right sphenoid wing in a 74-year-old woman. Histologically, it showed large areas of a typical meningothelial meningioma, among which numerous cartilaginous islands and some chondroid regions, obviously of intermediate (meningothelial/cartilaginous) differentiation, could be seen. Cartilaginous tumour areas showed lower MIB1-labelling indices than typical meningioma regions, where an increased proliferative activity was seen focally. The current WHO classification lists such tumours as metaplastic meningiomas, reflecting the potential of meningioma cells for mesenchymal differentiation. Metaplastic meningiomas may show different metaplasias (xanthomatous, osseous, lipomatous, cartilaginous, etc.). Extensive cartilaginous metaplasias are very uncommon. Identification of typical meningioma areas is the key for the diagnosis of this meningioma variant.

Aged↗
PubMed1992

Environmental tobacco smoke.

In 1992, the U.S. Environmental Protection Agency (EPA) issued a "draft" assessment of ETS and lung cancer in adults and respiratory disorders in children. Relying on weak and inconclusive epidemiological data, the supposed similarity between ETS and MS, the presence of "known or suspected carcinogens" in MS and by extrapolation in ETS, and the "biological plausibility" of an adverse relationship between ETS and health, the EPA recommended that ETS be classified as a "Group A (known human) carcinogen." Fundamental physical and quantitative chemical differences among ETS, MS, and SS and human exposure to each smoke were disregarded: The three are not equivalent nor is ETS exposure a quantitative variant of cigarette smoking. A substantial difference in retention percentage overlays the huge dosimetric difference between exposures. As a result, the "dosage" of ETS retained is miniscule relative to MS. Also, conclusions reached by the EPA and the use of tenuous relationships as bases for Group A classification are unwarranted because of failure to consider the data upon which the "tumorigenicity" of the ETS components was based, questions on the presence and/or levels of these components in MS, and data indicating that a 25- to 30-fold decrease of a high-level dose of MS or MS condensate diminished the effects observed in bioassays from pronounced to zero, i.e., a threshold was demonstrated. Finally, EPA overlooked the more than 100 tobacco smoke components known to inhibit the tumorigenic action of many of the listed "tumorigens."

Animals↗
PubMed2002

Discoid lateral meniscus in children.

The discoid meniscus is the most common abnormal meniscal variant in children. It is most likely a congenital deviation and usually occurs laterally. The discoid shape results in greater coverage of the tibia and usually is associated with increased thickness of the meniscus that may lead to abnormal shearing forces across the knee joint. The Watanabe classification divides this anomaly into three distinct types: complete, incomplete, and Wrisberg ligament. The complete and incomplete types are often asymptomatic; unless symptomatic, they generally should be left alone. Tears should be treated with resection back to a stable rim. The Wrisberg ligament type is a hypermobile meniscus secondary to a lack of posterior tibial attachment. This type may or may not be associated with an abnormal shape and may appear in childhood as a classic snapping knee syndrome. These children complain of intermittent popping and snapping within the knee that clinically manifests as a dramatic audible and visible adjustment of the knee with each flexion and extension. Treatment of a symptomatic Wrisberg ligament type requires surgical repair of the posterior disruption. Saucerization of the remaining meniscus may be required to protect the repair from abnormal shear forces.

Child↗
PubMed2004

Screening of HIV-1 isolates by reverse heteroduplex mobility assay and identification of non-B subtypes in Italy.

OBJECTIVE: The increasing prevalence of HIV-1 transmission through heterosexual contacts and the growing number of immigrants from non-Western countries, where non-B subtypes and recombinant forms are prevalent, suggest the possible emergence in Italy of a new epidemic wave of HIV-1 non-B subtypes as well as recombinant forms. METHODS: The distribution of HIV-1 subtypes has been evaluated in 63 seropositive individuals residing in Italy, most of whom were infected through a sexual route during the last 5 years. A modified heteroduplex mobility assay (HMA) strategy, reverse HMA (rHMA), has been developed in our laboratory, allowing rapid identification of divergent-from-B-subtype isolates, which have been subsequently characterized by detailed molecular and phylogenetic analyses. RESULTS: Five samples show, on rHMA, an electrophoretic pattern compatible with a non-B subtype classification. Their phylogenetic analysis, performed on both env and gag regions, confirms the rHMA subtyping prediction, given that 3 samples fall into the "A-family" subtype and 2 into the G subtype. The 5 non-B-subtype HIV-1 isolates have been identified among 23 variants (prevalence, 21.74%) isolated during the 2000 to 2001 period in heterosexuals. In parallel, B-subtype isolates show high levels of intrasubtype nucleotide divergence, compatible with a constant HIV-1 molecular diversification. CONCLUSION: The Italian HIV-1 epidemic is still mostly attributable to the B subtype, which shows an increasing nucleotide heterogeneity. Heterosexual transmission and the interracial blending, however, are slowly introducing novel HIV-1 subtypes, and the data indicate that rHMA represents a powerful tool for HIV-1 biomolecular screening in epidemics characterized by a mono-/dual-subtype predominance.

Adult↗
PubMed2004

Thermodynamical scaling of the glass transition dynamics.

Classification of glass-forming liquids based on the dramatic change in their properties upon approach to the glassy state is appealing, since this is the most conspicuous and often-studied aspect of the glass transition. Herein, we show that a generalized scaling, log (tau) proportional, variant T-1 V-gamma, where gamma is a material constant, yields superpositioning for ten glass formers, encompassing van der Waals molecules, associated liquids, and polymers. The exponent gamma reflects the degree to which volume governs the temperature and pressure dependence of the relaxation times.

Journal Article↗
PubMed1982

Genetic markers for schizophrenic subgroups.

By the study of hereditary serum protein markers in psychotic patients and normal controls, a surplus of Gc 1-1 (p less than 0.01) and transferrin B variants (p less than 0.0027) has been established in schizophrenias. Affective psychoses are characterized by an excess of the haptoglobin (Hp) serum type 2-2 (p less than 0.001). These general statements have to be modified in regard to the clinical and psychopathological subdivision beyond the traditional classification into two major groups of endogenous mental disease. Using Leonhard's criteria, the prevalence of Gc 1-1 is restricted to the systematic schizophrenias reaching its highest value in hebephrenias, which are followed by paraphrenic and catatonic forms in this trait. In contrast to this, periodical catatonia and affective paraphrenia, classified as subgroups of the unsystematic schizophrenias, have Gc 1-1 frequencies like healthy controls. On the other hand, the Hp 2-2 value is not increased in the systematic schizophrenias, but it displays a relative overplus in the unsystematic forms. Concerning the Hp 2-2 and Gc 1-1 frequencies a certain similarity can be observed between affective paraphrenia and the paranoid psychoses with late onset, it they are characterized by a cyclic axis syndrome as described by the Vienna school. The cycloid psychoses are marked by an extreme surplus of Hp 2-2 (p less than 0.001) and an overweight of Gc 1-1 (p less than 0.05). Probably the Gc and Hp alleles play a role as risk factors or accidental effectors in the multifactorial genetic systems responsible for the biological background of psychoses. For both serum systems a selective interaction is discussed considering the vitamin D transport by the Gc proteins with the relation to neuronal consolidation and the possible influence of Hp 2-2 on transport and receptor functions.

Alpha-Globulins↗
PubMed2000

Salivary gland basal cell and canalicular adenomas: immunohistochemical demonstration of myoepithelial cell participation and morphogenetic considerations.

OBJECTIVE: To evaluate cellular composition of salivary gland adenomas using 3 monoclonal antibodies that recognize a smooth muscle phenotype confirmed to be sensitive for myoepithelial differentiation. DESIGN: Immunohistochemical evaluation of 25 salivary gland basal cell and canalicular adenomas. SETTING: Archival pathology material from the files of Henry Ford Hospital, Detroit, Mich, and the University of California at San Francisco. RESULTS: All basal cell adenoma variants exhibit some degree of myoepithelial cell participation with periductal, epithelioid, and spindled (stromal-like) morphologic structures. Only the canalicular adenomas, even if mixed with trabecular and solid patterns, are devoid of staining with these 3 antibodies, suggesting an adenoma composed exclusively of ductal luminal cells. CONCLUSIONS: There is an overlapping histomorphologic and common cellular composition of the basal cell adenoma variants with other recognized adenomas, such as pleomorphic adenoma and myoepithelioma. Relative differentiation toward 3 cell phenotypes (ductal luminal, basal, and myoepithelial) and the character of extracellular matrix production in varying proportions by the neoplastic myoepithelial cells distinguishes the spectrum of salivary gland adenomas identified in current classification schemes.

Actins↗
PubMedDate not supplied

Serotyping of avian infectious bronchitis viruses by the virus-neutralization test.

The antigenic relationships of 12 strains of infectious bronchitis virus (IBV) were evaluated by a virus-neutralization procedure similar to that used in typing human rhinoviruses. Such a procedure consists of reciprocal neutralization tests performed by reacting 32-320 EID50 or plaque-forming units of virus with 20 antibody units of antiserum. Eight serologic groups were identified by chicken embryo assay, and 4 by plaque-reduction (90%). In general, serologic groupings were not distinct but reflected numerous intergroup relationships. The contrasting results exhibited by indicator systems are viewed as differences in the accuracy of the methods employed. It is suggested that before an IBV classification scheme can be proposed, agreement must be reached on the most suitable indicator system, techniques must be standardized, and reference viruses and antisera distributed to several institutions for comparison testing. In addition, cross-protection studies are needed to determine the importance of IBV serotypes and/or variants on vaccine efficacy.

Animals↗