DNA distribution pattern of the so-called severe dysplasias and small carcinomas of the colon and rectum and its possible significance in the tumor progression

The DNA distribution pattern was determined by cytofluorometry in 25 cases of colorectal small carcinoma and the so-called severe dysplasia. The colorectal carcinoma and "severe dysplasia" consisted of four principal stemlines as to DNA ploidy: diploidy, aneuploidy, and their respective polyploidies. These patterns appeared in various combinations in individual neoplasms. DNA distribution of the severe dysplasia was diploid-predominant (11 cases) or aneuploid-predominant (three cases), usually showing mosaicism in various degrees with respective first order polyploidy. Similar DNA distribution patterns also were found in submucosally invasive small carcinomas. The neoplastic cell populations of a higher polyploidy (second or third order), however, occurred only in the submucosally invasive carcinomas (three cases) regardless of their basic ploidy. The mitotic index tended to be higher in the aneuploid-predominant tumors than in the diploid-predominant tumors. In the current observation, there was no significant correlation between the DNA distribution pattern and histologic type of the "dysplasia" or carcinoma. We found that most of the so-called severe dysplasias of the colon and rectum already gained definitive characteristic of carcinoma in the DNA pattern, i.e., ploidy heterogeneity. Therefore, they can be identified as intramucosal carcinomas, distinct from the normal epithelia and adenomas of the colon and rectum.     

Discrete breakpoint mapping and shortest region of overlap of chromosome arm 1q gain and 1p loss in human hepatocellular carcinoma detected by semiquantitative microsatellite analysis

Recurrent chromosomal gain at 1q is one of the most common features of human hepatocellular carcinoma (HCC), but how the gain at 1q contributes to hepatocarcinogenesis is still unclear. To identify the target genes, precise determination of the shortest region of overlap (SRO) and of breakpoints is necessary. Similarly, the role of loss at 1p, which is also a major cytogenetic aberration in HCC, needs to be determined. Fifty HCCs were examined with the aid of 59 microsatellite markers distributed throughout both arms of chromosome 1. To detect allelic gain effectively, the cutoff value of the allelic imbalance index was set at 0.70. Alleles showing imbalance were subjected to multiplex PCR, using a retained allele as an internal control, to determine whether the imbalance was the result of chromosomal gain or loss. The SRO of the gains was defined as D1S2878-D1S2619 (1q23.-q25.3, 16.9 Mb), which involved 36 cases (72%). Gains in the number of copies of certain oncogenes within this region seemed to be critical for the pathogenesis of HCC. In contrast, the centromeric breakpoints of these gains varied, but they tended to occur mainly in the pericentromeric region (26 of 50 cases, 52%). Rearrangement of specific genes associated with the gains is unlikely. On the other hand, the SRO of deletion was defined as D1S2893-D1S450 (1p36.32-p36.22, 5.1 Mb). Four known putative tumor-suppressor genes (TP73, RIZ1, NBL1/DAN, and CDKN2C) were outside the SRO, suggesting the presence of other candidate genes with critical roles in hepatocarcinogenesis.     

A novel t(2;6)(p12;q23) appearing during transformation of follicular lymphoma with t(18;22)(q21;q11) to diffuse large cell lymphoma

Follicular lymphoma is characterized genetically by t(14;18)(q32;q21), whereas t(18;22)(q21;q11), a rare variant form of t(14;18), has been preferentially observed in chronic lymphocytic leukemia (CLL). We describe here an unusual case of follicular lymphoma with a t(18;22)(q21;q11), that progressed to diffuse large cell lymphoma with a novel t(2;6)(p12;q23). Spectral karyotyping revealed that add(2)(p12) and add(6)(q23) were derived from a t(2;6)(p12;q23). Fluorescence in situ hybridization analysis confirmed rearrangements of the BCL2 gene at 18q21 and the BCL6 gene at 3q27. Our results indicate that a reciprocal translocation involving 6q23 could be implicated in the progression of follicular lymphoma and that t(18;22) may have a specific role in the pathogenesis of follicular lymphoma as well as CLL.     

The effect of inflammatory cytokines on secretion of macrophage colony-stimulating factor and monocyte chemoattractant protein-1 in human granulosa cells

PROBLEM: In order to investigate the role of macrophage colony-stimulating factor (M-CSF) and monocyte chemoattractant protein -1 (MCP-1) in human ovulation, we studied the regulation of M-CSF and MCP-1 in cultured human granulosa cells. METHOD OF STUDY: Immortalized granulosa cells (GC1a) were cultured in serum-free medium, and incubated with interleukin (IL)-1alpha, IL-1 receptor antagonist (ra) and tumor necrosis factor (TNF)-alpha. The supernatants were collected, and M-CSF and MCP-1 were measured by ELISA. RESULTS: The levels of M-CSF and MCP-1 were increased after treatment with IL-1alpha (1 nm) and TNF-alpha (1 nm) in a time-dependent manner. The levels of M-CSF and MCP-1 were significantly increased after treatment with IL-1alpha and TNF-alpha in a dose-dependent manner. However, the levels of M-CSF and MCP-1 were significantly decreased by treatment with IL-1alpha (1 nm) and/or increasing concentrations of IL-1 ra. CONCLUSIONS: Our data indicated that M-CSF and MCP-1 were regulated by IL-1alpha and TNF-alpha. It was suggested that M-CSF and MCP-1 may play an important role in human preovulatory processes.     

Murine thymic nurse cell clone supports the growth of fetal thymocytes in the presence of interleukin 2.

To investigate the role of thymic nurse cells (TNC) in activation and differentiation of fetal CD4-CD8- (double-negative) thymocytes, we have co-cultured murine fetal thymocytes (14-15 days of gestation) with an established murine TNC clone. We show here that TNC induced the growth of the fetal double-negative thymocytes in the presence of recombinant interleukin 2 (rIL2). Activated fetal thymocytes markedly formed lymphocyte-TNC complexes and proliferated extensively after 5 days in the co-culture. The activated fetal thymocytes in this co-culture condition remained double negative after 10 days in culture. None of them gave rise to phenotypically and functionally competent lymphocytes during this period. TNC alone and the supernatant of TNC had no effect on activation. The presence of both TNC and rIL2 was necessary for the growth of fetal thymocytes in our system. The proliferation of fetal thymocytes was inhibited by a monoclonal antibody against mouse IL2 receptors (IL2R). The fetal thymocytes could be maintained further in this co-culture condition. The prolonged cultivation of fetal thymocytes resulted in the establishment of the fetal thymocyte line and its several clones. CD4 single-positive cells of activated fetal thymocytes first appeared 14 days after the onset of culture and their number increased, whereas CD8+ cells or CD4CD8 double-positive cells were not observed. These results indicate that fetal CD4-CD8- thymocytes underwent phenotypic change after long periods of culture. All established clones of fetal thymocytes are CD4 single positive showing lymphocyte-TNC interactions but do not express CD3 complex. Northern blot analysis detected mRNA for the gamma T cell receptor, but no messages for the delta, alpha or beta T cell receptor. Chemical cross-linking of 125I-labelled IL2 revealed that the 90-kDa band (presumably considered to be the IL2R beta chain) was clearly present in IL2-responsive fetal clones, whereas freshly isolated day 14-15 fetal thymocytes lacked the band. Taken together, TNC might be involved in the differentiation and/or expansion of murine fetal thymocytes by inducing IL2R beta chain, which forms the functional IL2R together with IL2R alpha chain and CD4, one of the T cell accessory molecules, on the cell surface through direct cell-cell interaction.     

The ultrasound examination of the deep vein thrombosis

Ultrasonography is very useful for detection of deep vein thrombosis. The purpose of this paper is to show a method for detecting them efficiently by high resolution transducer and color Doppler system. We examined patients in the supine and prone positions. To detect the venous flow easily and differentiate thrombi from simple venous dilatation, some maneuvers are useful; one is pushing the vein area using the transducer on examination, the second is breathing overload, and the last is so-called milking. We can find throombi in the external iliac or femoral veins of patients who have symptoms of lower leg swelling, however, we need to better detect venous thrombi in the lower leg in patients with a history of pulmonary embolism. Because deep venous thrombi are increasing, the role of ultrasound will expand in the future.     

Granulocytic sarcoma presenting with lymph node infarction at disease onset

A completely infarcted lymph node is an unusual event. However, lymph node infarction should alert the pathologist to the considerable likelihood of malignant lymphoma. We report two unusual cases of acute myeloid leukemia presenting with granulocytic sarcoma at disease onset with a lymph node lesion exhibiting extensive lymph node infarction. The infarcted tissue contained numerous eosinophilic cell ghosts. There were some islands of degenerated, pyknotic medium-sized nuclei resembling lymphoblasts present in the necrotic area. By immunohistochemistry, these medium sized cells were CD3-, CD20-, CD34+, CD43+, CD45RO-, CD68-, CD79a- and myeloperoxidase+ in both cases. Differentiation of granulocytic sarcoma from malignant lymphomas is important for adequate therapy. The present cases indicate that granulocytic sarcoma should be added to the list of differential diagnoses for lymph node infarction.     

Effect of increased task procedures on correlation dimensions of the electroencephalogram

Changes in correlation dimensions of the electroencephalogram (EEG) were examined in three different tasks. These three tasks differed from each other with respect to the number of procedures. In the present experiment, left-hand movement and mental arithmetic were controlled, respectively, during an auditory linguistic task. Subjects were 13 healthy right-handed males. EEG signals from eight electrode sites were analyzed and the correlation dimensions were obtained. In addition, the relative power was obtained for the alpha band. An increase in the number of procedures yielded high dimensionality on the occipital EEG. In contrast, left-hand movement had no significant effect on EEG dimensions over the motor area. The relative power of the alpha band was seen to decrease in all channels as the number of procedures increased. The fact that changes in EEG dimensions did not necessarily exhibit a simple correspondence to changes in alpha wave activity was also discussed.     

Polyarteritis Nodosa with Atrophy of the Left Hepatic Lobe

A 73-year-old Japanese man with a history of partial gastrectomy due to gastric cancer 4 years previously was admitted because of intermittent fever. The patient developed abdominal pain, erythema, and myalgia in addition to the fever during the final clinical course, and died of acute heart failure. Autopsy disclosed atrophy of the left lobe of the liver and acute myocardial infarction. Neither metastasis nor recurrence of the cancer was observed. Small and medium-sized arteries of the visceral organs showed various stages of necrotizing vasculitis with narrowing of the lumina. The vasculitis was most prominent in the left lobe of the liver and in the heart. Narrowing of the portal vein due to portal tract inflammation in addition to vasculitis of the hepatic arteries may have induced ischemia and infarction, which had resulted in atrophy of the left hepatic lobe. Acta Pathol Jpn 42: 662–666, 1992.     

Neuronal histamine inhibits methamphetamine-induced locomotor hyperactivity in mice

Mianserin (5-20 mg/kg), like chlordiazepoxide (2.5-10 mg/kg), inhibits the shock-induced suppression of drinking (SSD) in rats. However, in contrast to chlordiazepoxide, the effect of mianserin is not blocked by the benzodiazepine antagonist, Ro 15-1788 (10 mg/kg). Although mianserin does not inhibit [3H]diazepam binding in vitro it has now been found to enhance [3H]flunitrazepam binding to mouse whole brain in vivo at 10-100 mg/kg p.o. These results suggest that mianserin does influence central benzodiazepine receptors, but the mechanism by which it does so differs from that of chlordiazepoxide.