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Somatic G17V RHOA mutations were found in 50–70% of angioimmunoblastic T-cell lymphoma (AITL). The mutant RHOA lacks GTP binding capacity, suggesting defects in the classical RHOA signaling. Here, we discovered the novel function of the G17V RHOA: VAV1 was identified as a G17V RHOA-specific binding partner via high-throughput screening. We found that binding of G17V RHOA to VAV1 augmented its adaptor function through phosphorylation of 174Tyr, resulting in acceleration of T-cell receptor (TCR) signaling. Enrichment of cytokine and chemokine-related pathways was also evident by the expression of G17V RHOA. We further identified VAV1 mutations and a new translocation, VAV1–STAP2, in seven of the 85 RHOA mutation-negative samples (8.2%), whereas none of the 41 RHOA mutation-positive samples exhibited VAV1 mutations. Augmentation of 174Tyr phosphorylation was also demonstrated in VAV1–STAP2. Dasatinib, a multikinase inhibitor, efficiently blocked the accelerated VAV1 phosphorylation and the associating TCR signaling by both G17V RHOA and VAV1–STAP2 expression. Phospho-VAV1 staining was demonstrated in the clinical specimens harboring G17V RHOA and VAV1 mutations at a higher frequency than those without. Our findings indicate that the G17V RHOA–VAV1 axis may provide a new therapeutic target in AITL.

Genome studies of diffuse large B-cell lymphoma (DLBCL) have revealed a large number of somatic mutations and structural alterations. However, the clinical significance of these alterations is still not well defined. In this study, we have integrated the analysis of targeted next-generation sequencing of 106 genes and genomic copy number alterations (CNA) in 150 DLBCL. The clinically significant findings were validated in an independent cohort of 111 patients. Germinal center B-cell and activated B-cell DLBCL had a differential profile of mutations, altered pathogenic pathways and CNA. Mutations in genes of the NOTCH pathway and tumor suppressor genes (TP53/CDKN2A), but not individual genes, conferred an unfavorable prognosis, confirmed in the independent validation cohort. A gene expression profiling analysis showed that tumors with NOTCH pathway mutations had a significant modulation of downstream target genes, emphasizing the relevance of this pathway in DLBCL. An in silico drug discovery analysis recognized 69 (46%) cases carrying at least one genomic alteration considered a potential target of drug response according to early clinical trials or preclinical assays in DLBCL or other lymphomas. In conclusion, this study identifies relevant pathways and mutated genes in DLBCL and recognizes potential targets for new intervention strategies.

Frazil ice in the coastal polynyas has been increasingly recognized as important for efficient sea ice production, associated dense water formation, transport of particulate matter and consequent biological production. However, it has not been well understood where and to what degree active‐frazil areas occur in the Northern Hemisphere polynyas. We presented the first mapping of active frazil in the Northern Hemisphere, using sea ice data during September–May for 2002/2003–2010/2011, created from an Advanced Microwave Scanning Radiometer for the Earth Observing System thin ice algorithm that can detect active frazil areas. The North Water, Northeast Water, Anadyr, and St. Lawrence Island polynyas were found to have a relatively high occurrence rate of active frazil compared with other polynyas. We improved the estimation of sea ice production by discriminating between active frazil and thin solid ice and found that previous algorithms tended to overestimate sea ice production, particularly for polynyas dominated by thin solid ice such as the Okhotsk Northwestern polynya. We also made the first global comparison of polynya characteristics for all the major coastal polynyas. The annual ice production rate is 3–4 m yr−1in the Northern Hemisphere polynyas and 6–9 m yr−1in the Antarctic coastal polynyas. This large difference is mainly explained by the less frequent occurrence of active frazil and thin ice areas in the Northern Hemisphere polynyas owing to a lower occurrence of strong wind events. Coastal polynyas, which are high‐latitude coastal regions of thin ice or open water surrounded by thick sea ice, are important components of the global climate system. High production of sea ice in coastal polynyas generates dense water, which then influences physical and biological processes in the surrounding regions. Thin ice areas in a polynya are roughly classified into two ice types: active frazil, a mixture of grease/frazil ice and open water formed under turbulent conditions, and thin solid ice, a relatively uniform thin ice region formed under calm conditions. In this study, we focused on measuring the active frazil, which indicates areas of efficient ice production. Frazil ice also incorporates and transports sediments or micro‐nutrients, possibly leading high biological productivity. We presented the first mapping of active‐frazil areas in the Northern Hemisphere, and improved estimates of total ice production taking account of the ice type. We also discussed the characteristics of major coastal polynyas in the world. The rates of ice production and active frazil occurrence are generally lower in the Northern Hemisphere than in the Antarctic coastal polynyas because of lower wind speeds in the Northern Hemisphere high‐latitude coastal regions. The active frazil area in the Northern Hemisphere is mapped for the first time, with improved estimation of sea ice productionSeveral coastal polynyas with a high occurrence rate of active frazil and high ice production rate are extractedThe ice production rate in Northern Hemisphere polynyas is generally lower than in Antarctic polynyas owing to fewer strong wind events The active frazil area in the Northern Hemisphere is mapped for the first time, with improved estimation of sea ice production Several coastal polynyas with a high occurrence rate of active frazil and high ice production rate are extracted The ice production rate in Northern Hemisphere polynyas is generally lower than in Antarctic polynyas owing to fewer strong wind events

Numerous antral follicles develop during the second half of pregnancy in the golden hamster. However, mechanisms regulating follicular development during this period are unknown. Because inhibin and activin are related to follicular development, these hormones were studied to gain insight into any potential roles in follicular development. Plasma inhibin A and B suddenly increased from day 8 of pregnancy, reached peak levels on day 10 and gradually declined to term. Plasma activin A gradually increased from day 8 to day 15 of pregnancy, and this was followed by an abrupt decrease at day one of lactation. Ovariectomy on day 12 of pregnancy rapidly reduced plasma inhibin A and B, but not activin A levels. Hysterectomy or placentectomy on day 12 of pregnancy caused an abrupt decrease in the levels of plasma activin A and FSH, but not inhibin A and B at 6 h after surgery. Hysterectomy also induced atresia of large antral follicles at 24 h after surgery. These results indicate that antral follicles are the main source of circulating inhibin A and B, whereas uteri and placentae are the main source of circulating activin A. These results suggest that increased levels of activin A may be involved in folliculogenesis in the ovary during the second half of pregnancy in the golden hamster.

Immunohistochemical studies on the time-dependent expression of the chemokines such as interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1α were performed on 50 human skin wounds with different wound ages (group I 0–12 h, group II 1–4 days, group III 7–14 days and group IV 17–21 days). In the wound specimens with wound ages between 4 and 12 h, neutrophils mainly showed positive reactions for IL-8, MCP-1 and MIP-1α. With increasing wound ages, macrophages and fibroblasts were positively stained with anti-IL-8, MIP-1α and MCP-1 antibodies. Morphometrically, there was a similar distribution in the positive ratios of the inflammatory cells among IL-8, MCP-1 and MIP-1α. The positive ratios of each chemokine were very low in group I and a considerable increase of the positive ratios in each chemokine was observed in group II (mean ± standard error IL-8: 59.8 ± 2.1%, MCP-1: 42.4 ± 3.1% and MIP-1α: 50.4 ± 3.7%). Although the positive ratios for each chemokine gradually decreased according to the wound age, the mean positive ratios in groups III and IV were significantly higher than those in group I. From the forensic aspect, these chemokines are considered useful markers for wound age determination. Thus, ratios of > 50% for IL-8, > 30% for MCP-1 or > 40% for MIP-1α indicate a wound age of at least 1 day. Moreover, the combined investigation of these three chemokines can make wound age determination more objective and accurate.

The changes in plasma concentrations of inhibins A, B and pro-alpha C were determined in the cyclic golden hamster during follicular atresia induced with antiserum against luteinizing hormone releasing hormone (LHRH-AS) at 1100 h on day 4 (day 1=day of ovulation). Follicular status in the ovary was also studied by determining the number of follicles ovulating in response to human chorionic gonadotrophin (hCG) injection. The time-courses of changes in plasma concentrations of inhibins A, B and pro-alpha C were different from each other during induced follicular atresia and subsequent follicular development. Plasma concentrations of inhibin A decreased to 58.6% of initial values by 24 h after LHRH-AS treatment, and then remained relatively low until at least 60 h later. Plasma concentrations of inhibin B decreased to 64.2% of the initial values by 18 h after LHRH-AS treatment and remained at basal values for 36 h, but increased abruptly to greater than initial values at 42 h after the treatment. Plasma concentrations of inhibin pro-alpha C increased at 6 and 12 h, decreased suddenly to 21.9% of the initial values by 24 h after LHRH-AS treatment, and then gradually increased until 60 h after LHRH-AS. The number of follicles responding to hCG decreased gradually between 0 and 30 h after LHRH-AS, when no ovulations were observed, and then gradually increased until 60 h. The changes in follicular ovulatory responses to hCG correlated with the plasma profile of inhibin A throughout the experiment. These results suggest that inhibin A is mainly secreted by large antral follicles. In contrast, during the subsequent follicular development, the plasma concentration of inhibin B increased earlier than that of inhibin A. These results suggest that inhibin B is secreted by small and large antral follicles. Plasma concentrations of inhibin pro-alpha C were high at a time when plasma concentrations of oestradiol-17 beta had already decreased, indicating that inhibin pro-alpha C is secreted not only from healthy follicles but also from early atretic antral follicles.

Intravascular large B-cell lymphoma (IVLBL) is a rare neoplasm characterized by proliferation of lymphoma cells within the blood vessels. The cell origin of IVLBL has not yet been determined. We examined cell lineage, with immunohistochemical staining and molecular analysis, using polymerase chain reaction (PCR) of the variable region of the immunoglobulin heavy chain (Ig-VH) gene. We also investigated the cell origin using direct sequence analysis of the complementary-determining region 2 (CDR2) and framework region 3 (FR3) in six cases, consisting of two male and four female patients. The sequences in five cases showed frequent mutations. The percent homology to their closest germline genes ranged from 74.7 to 91.8%. However, one case showed a percent homology of 99.4% in CDR2 and FR3 of Ig-VH. All cases showed rearrangements of VH3 family genes. Interestingly, three of the IVLBL cases with hypermutated IgH genes showed the expression of CD5. Therefore, expression of CD5 in lymphoma cells does not indicate that the origin of IVLBL is the same as mantle cell lymphoma having the character of CD5 expression, which develops in pre-germinal center cells. Our results indicate that most IVLBLs may originate in the post-germinal center cells, based on the presence of somatic mutation in VH genes, although some heterogeneous cases are intermingled within IVLBL.

Abstract: We encountered a patient with Sjögren's syndrome (SS) associated with bilateral parotid salivary gland swelling. Histological analysis of biopsy specimens from both parotid glands showed myoepithelial islands and infiltration of small- and intermediate-sized lymphocytes but no cytological atypia. Using reverse transcriptase-polymerase chain reaction and subsequent single-strand conformational polymorphism analysis, monoclonal B-cell expansion was detected in samples from both right and left parotid glands, bone marrow, and peripheral blood (PB). Our case suggests that the circulating clonal lymphocytes represent clones that can repopulate tissue sites and may contribute to B-cell lymphomagenesis. Detection of monoclonal B cells in PB is therefore considered to be important in monitoring the disease course of SS.

AbstractWe encountered a patient with Sjögren's syndrome (SS) associated with bilateral parotid salivary gland swelling. Histological analysis of biopsy specimens from both parotid glands showed myoepithelial islands and infiltration of small- and intermediate-sized lymphocytes but no cytological atypia. Using reverse transcriptase-polymerase chain reaction and subsequent single-strand conformational polymorphism analysis, monoclonal B-cell expansion was detected in samples from both right and left parotid glands, bone marrow, and peripheral blood (PB). Our case suggests that the circulating clonal lymphocytes represent clones that can repopulate tissue sites and may contribute to B-cell lymphomagenesis. Detection of monoclonal B cells in PB is therefore considered to be important in monitoring the disease course of SS.

Abstract: Cytotoxic cells include natural killer (NK) cells and cytotoxic αβ and γδ T lymphocytes (CTLs). These cells express cytotoxic molecules of T-cell restricted intracellular antigen(TIA-1), and activated cytotoxic molecules of perforin, granzyme B, and FasL. Recent studies suggest that most extranodal T-cell lymphomas are derived from CTLs, and that NK cell lymphomas are extranodal. However, only a few nodal NK and cytotoxic lymphomas have been described so far. We present here the clinicopathological features of seven cases of nodal cytotoxic T and NK cell lymphomas. The study excluded anaplastic large-cell lymphomas expressing cytotoxic molecules. The neoplastic cells of all cases contained activated cytotoxic molecules of TIA-1, granzyme B, Fas ligand, and/or perforin. Phenotypically and genotypically, four cases showed αβ T cell type [CD2+, CD3+, T-cell receptor (TCR) δ-1–, βF1+, and TCR gene rearrangement], two cases showed γδ T-cell type [CD2+, CD3+, T-cell receptor (TCR)δ–1+, βF1–, and TCR gene rearrangement], and one case showed NK cell type [CD2+, CD3-, CD56+, T-cell receptor (TCR)δ-1–, βF1–, and TCR gene germline]. Using Southern blot analysis, Epstein-Barr virus (EBV) sequences were detected in six cases, and monoclonal terminal repeat proliferation was confirmed. In addition, in situ hybridization (ISH) studies for EBV showed EBV infection in almost all neoplastic cells. Clinically, all patients presented with peripheral lymphadenopathy in high clinical stages and showed an aggressive course. Hepatosplenomegaly was detected in six cases. During the course of the disease, bone marrow and extranodal invasion were noted in five cases. The nodal type showed an aggressive clinical course in all cases but one, as did the extranodal type. The nodal type varied in phenotype, but was closely associated with EBV infection.

An individual with late-onset ataxia was found to be heterozygous for an unusual (GAAGGA)65sequence and a normal GAA repeat in the frataxin gene. No frataxin point mutation was present, excluding a form of Friedreich ataxia. (GAAGGA)65did not have the inhibitory effect on gene expression in transfected cells shown by pathogenic GAA repeats of similar length. GAA repeats, but not (GAAGGA)65, adopt a triple helical conformation in vitro. We suggest that such a triplex structure is essential for suppression of gene expression.

The seasonal variations in serotonin immunoreactivity and ultrastructure of the secretory rudimentary photoreceptor cells (SRPC) were studied in the pineal organ of the Japanese grass lizard, Takydromus tachydromoidesin relation to the environmental temperature. Our results clearly demonstrated that serotonin immunoreactivity in the lizard pineal organ displayed seasonal variations under an artificial photoperiod of LD 12:12 and natural temperature in the laboratory. Immunoreactivity became intense with increase in temperature from spring to summer, showing the strongest reaction in the summer, and subsequently became weak with the drop in temperature to winter. Also, the SRPC of the lizard showed distinct seasonal variations in number and size of the dense-cored vesicles correlated to the serotonin immunoreactivity. In contrast, the changes in size of the lysosomes and nucleoli of the SRPC were inversely proportional to that of the dense-cored vesicles. Furthermore, the lysosomes ingested some dense-cored vesicles after the autumn, and they coalesced to form huge autophagosomes or residual bodies during the winter. The present study provided serotonin-immunohistochemical and ultrastructural evidence for seasonal variations in the secretory activity of the lizard pineal organ in accordance with changes in the environmental temperature. However, there may be few functional relationships between the pineal gland and the reproductive organs in the male Japanese lizard in relation to environmental temperature.

The reaction of the five-membered cyclic oxosulfonium ylide 2 with α-methylene-β-acetoxy ketones in the presence of two equimolar amounts of base afforded the cycloheptene oxide derivatives with stereoselectivity in 19−74% yield via a Michael-type addition of the ylide followed by elimination of the acetoxy group and an intramolecular Corey-Chaykovsky reaction.

The fine structure and immunocytochemical localization of serotonin in the cells of the receptor line were studied in the parietal eye and pineal organ proper of the Japanese grass lizard,Takydromus tachydromoides. Typical photoreceptor cells (PC) were the predominant cell type in the receptor line of the parietal eye, the outer segments of which had regular stacks of numerous disks similar to those of cones. The pineal organ contained relatively few PCs, which showed less well-developed outer segments than those of the parietal eye. In contrast, secretory rudimentary photoreceptor cells (SRPC) accounted for the majority of receptor cells in the pineal organ. These cells were structurally characterized by whorl-like lamellar outer segments and numerous dense-cored vesicles (80–280 nm in diameter). A small number of SRPC were also found in the parietal retina, which were similar to those in the pineal organ. In the parietal–pineal complex, numerous mitochondria located in the PC were larger and rounder than those in the SRPC. In the PC, basal processes prossessed only synaptic ribbons, whereas in the SRPC some of these processes contained synaptic ribbons and others contained dense-cored vesicles, rarely having both. Serotonin-immunoreactive cells were found not only in the pineal organ but also in the parietal eye, which closely resembled the cells of the receptor line in their size and shape. Furthermore, on immunoelectron microscopy for serotonin using the protein A-gold technique, gold particles indicating serotonin-immunoreactive sites were restricted in the core of dense-cored vesicles in the SRPC of the pineal organ. Regional differences in the distributions of the PC, SRPC and serotonin-immunoreactivity were found in the parietal-pineal complex.

Abstract: Adult T-cell leukaemia/lymphoma (ATLL) cells usually exhibit a CD4+ (helper/inducer) phenotype (CD4+/8–/56–), and only a minority of tumours express the CD8 (cytotoxic/suppressor) or CD56 (natural killer [NK]-associated) antigens. TIA-1 is a cytotoxic granule-associated protein expressed in NK cells and cytotoxic T lymphocytes (CTLs). Granzyme B, perforin and Fas ligand (FasL) are also expressed in activated CTLs and NK cells. To clarify the cytotoxic potential of ATLL cells, immunohistochemistry was performed in CD8+ and/or CD56+ ATLL cells, using anti-TIA-1, anti-granzyme B, anti-perforin and anti-FasL antibodies. We studied nine cases of CD8+ and/or CD56+ ATLL, all of which exhibited monoclonal integration of human T-cell leukaemia virus type 1 (HTLV-1) proviral DNA. Four cases exhibited a CD8+/CD56– phenotype, four others had a CD8–/CD56+ phenotype, and one was CD8+/CD56+. All but one case also expressed the surface antigens CD3, TCR αβ, and CD4. Expression of granzyme B and TIA-1 were demonstrated in three and two cases, respectively, but none expressed perforin or FasL. In the control study, 10 cases with typical CD3+/4+/8–/56– ATLL demonstrated no expression of those cytotoxic-associated proteins. Our findings suggest that CD8 and/or CD56 positivity probably confer(s) no cytotoxic function on ATLL cells, and it is possible that CD8 and CD56 may be simply aberrant surface markers in ATLL.

Plasma concentrations of inhibin pro-alphaC, inhibin A and inhibin B were determined by enzyme-linked immunosorbent assay at 6 h intervals throughout the 4-day oestrous cycle of the golden hamster. Plasma concentrations of follicle-stimulating hormone (FSH) and oestradiol-17beta were also measured by radioimmunoassay during the oestrous cycle. Plasma concentrations of inhibin A increased from the early morning of day 1 (day 1=day of ovulation) and reached plateau levels at 0500 h on day 2. An abrupt increase in plasma concentrations of inhibin A was found at 1700 h on day 4, when the preovulatory FSH surge was observed. An increase in plasma concentrations of inhibin B occurred on day 1 and reached plateau levels at 1700 h on day 1. The levels remained elevated until 0500 h on day 4 and declined gradually by 2300 h on day 4. Plasma concentrations of inhibin pro-alphaC gradually increased with some fluctuation from day 1 to 1700 h on day 4 and then declined. Significant negative relationships were noted between plasma FSH and both dimeric forms of inhibin from day 1 to day 3. Significant positive relationships were found between plasma oestradiol-17beta and inhibin A or inhibin pro-alphaC throughout the oestrous cycle. In contrast, no significant relationship was found between plasma oestradiol-17beta and inhibin B. These findings suggest that both dimeric forms of inhibin play a role in the regulation of FSH secretion during follicular development. These findings also suggest that inhibin pro-alphaC could be secreted primarily by large follicles, and early atretic follicles could also be responsible for inhibin pro-alphaC secretion. On the other hand, the secretory pattern of dimeric inhibins might shift from inhibin B to inhibin A with follicular development.

An interactive online simulator PASS (Predictive Adaptive Simulation System) has been developed as a packaged tool for predictive production control systems. PASS is a man-machine system to enhance the following functions: prediction of process status and evaluation of alternative precautionary measures. In this paper, the present version (a job shop model) is described in terms of the prediction and evaluation functions, the simulation model, and the software structure

Summary The nucleotide sequences of coat protein (CP) genes of two Japanese strains of melon necrotic spot virus·(MNSV-NH and MNSV-S) were determined. The size of the CP genes of both strains was 1170 nucleotides. Comparisons of the deduced amino acid sequences among MNSV strains showed more than 95% homology, and those among other carmoviruses showed 31–34% homology. cDNAs of MNSV CP genes were cloned into anEscherichia coli expression fusion vector and MNSV-NH and MNSV-S CPs were successfully produced. Furthermore, synthetic oligonucleotide primers were used for differentiating MNSV strains by reverse transcription-polymerase chain reaction method.

We analysed the expression of adhesion molecules on lymphoma cells in 13 patients with Ki-1 (CD30)-positive anaplastic large-cell lymphoma (Ki-1 ALCL; lymph nodes in 6, extranodal tumours in 6, and both lymph nodes and bone in 1). Very late activation antigen (VLA)-a4 (CD49d) and Hermes lymph node homing receptor (CD44) were constantly expressed in all specimens, and intercellular adhesion molecule-1 (ICAM-1; CD54) was frequently expressed in 10 of the 14 specimens. The expressions of lymphocyte function-associated antigen-1a (LFA-1a; CD11a) and VLA-a5 (CD49e) occurred in 5 of 14 and 4 of 14 specimens, respectively. The expressions of VLA-a2 (CD49b), endothelial leukocyte adhesion molecule-1, neural cell adhesion molecule (CD56) and E cadherin were always lacking. VLA-a6 (CD49f) was absent in all but one specimen. The expression of VLA-a5 on Ki-1 ALCL was high in subcutis-cutis but absent in lymph nodes. Furthermore, in one case, LFA-1a was detected in the primary lymph node, but was absent in a metastatic bone lesion. These results suggest that the expression of ICAM-1 is partially responsible for aleukemic behaviour in Ki-1 ALCL and, moreover, that the Ki-1 ALCL cells modify their expression of adhesion molecules at each of the involved organs.

The transition between atypical hyperplasia and lymphoma with angioimmunoblastic lymphadenopathy and dysproteinaemia (AILD) was studied in serial lymp node biopsy specimens from five patients using DNA analysis with Southern blot analysis, polymerase chain reaction, chromosomal analysis, and immunophenotyping. The chromosomal analysis showed additional abnormalities as the disease progressed to those present initially, and immunological staining showed a corresponding increase in the numbers of CD4- and Ki67-positive cells. In the first biopsy from each patient a diagnosis of atypical hyperplasia with AILD was made and lymphoma excluding by the finding of only a few atypical lymphoid cells and the preservation of follicles with germinal centres. DNA analysis of lymph nodes at this stage showed either germ lines or oligoclonal rearrangements of the T-cell receptor (TCR) and immunoglobulin heavy chain genes. In the final biopsy, when a diagnosis of lymphoma with AILD was made, either a monoclonal rearrangement of the TCR was observed or one of the rearranged bands had increased in density. These results suggest selective proliferation of a clone of abnormal cells may account for the progression of atypical hyperplasia to lymphoma with AILD.

To examine the relationship between the expression of human T-cell leukaemia virus type (HTLV-I) mRNA and associated antigens and clinicopathological features, we studied 31 lymph nodes of patients with adult T-cell leukaemia/lymphoma (ATLL) and related diseases, using in situ hybridization and immunohistochemistry. We classified the patients into four types on the basis of their clinicopathological features (HTLV-I associated lymphadenitis, incipient ATLL, ATLL with complete HTLV-I provirus, and ATLL with defective HTLV-I provirus. The expression of HTLV-I mRNA was detected in all 3 patients with incipient ATLL, in 5 of 10 patients with defective-provirus ATLL, in 5 of 11 patients with complete-provirus ATLL, and 3 of 7 with HTLV-I associated lymphadenitis, but the amounts were very small; approximately 1 in 10000–200000 lymph node cells express the viral genomes. This suggests that expression of viral genomes may not be important for immortalization, but it is important that to note the capacity for HTLV-I infection is preserved in each group of non-neoplastic and neoplastic states. HTLV-I mRNA was detected only in lymphocytes and/or lymphoma cells, but the HTLV-I associated antigens (env, gag and pX) were found in histiocytes and endothelial cells, as well as in lymphocytes and/or lymphoma cells. Anti-interleukin 2 receptor (IL-2R) antibody reacted with the giant cells of incipient ATLL and with the transformed lymphocytes and immunoblast-like cells of the HTLV-I-associated lymphadenitis but not with the lymphocytes in the background. Of the typical ATLL, IL-2R was found in both lymphoma cells and giant cells. IL-2 was rarely detected.

We investigated three patients suffering from angiocentric lymphoma with granulomatous panniculitis in the skin. All three patients presented with multiple purple subcutaneous nodules. Immunohistologically, the lymphoma cells in all three patients expressed CD2 (T-11), CD56 (neural cell adhesion molecule), and Mik-ß1 (interleukin-2ß receptor). CD3s (CD3, Leu-4)-positive lymphoma cells were found in two patients. A pore-forming protein (perforin) was detected in the lymphoma cells of all three patients. Perforin-possessing lymphoid cells were focally scattered in 2 of 15 patients with CD56-negative cutaneous lymphomas who served as controls. By the Southern blot method, one patient showed a rearranged T-cell receptor (TcR)ß gene in the biopsied specimen, and the other two patients had germline configurations of TcRs and immunoglobulin heavy chain genes. One patient had serum anti-human T-cell lymphotropic virus (HTLV)-I antibody, but showed no integration of its proviral DNA. Ultrastructurally, membrane-bound azurophilic granules were detected in the atypical lymphoid cells of all three patients. Angiocentric lymphoma with panniculitis in three patients showed the characteristics of natural killer and large granular T-cells. The histological features might be due to the characteristics of the neoplastic cells with azurophilic granules and perforin.

The alpha -particle-induced soft-error phenomena for VLSIs are investigated using a three-dimensional device simulator and a new experimental method. The scope of the present work includes a description of: the scalability of the funneling length (size effects and proximity effects), the effects of reduced supply voltages, the potential barrier effect of an n/sup +/-p/sup +/-p (substrate) structure, compulsory exposure experiments, and a new effect that causes the soft error ( alpha -particle source-drain penetration effect, or ALPEN). A new funneling length behavior that cannot be explained by Hu's model (1982) is discussed. According to this behavior, it was found that a critical charge for a given soft-error rate, which determines the limitation of planar and trench memory cells, can be scaled down. Furthermore, it is shown that the ALPEN effect, which occurs when an effective channel length of a MOSFET is comparable to the effective funneling length, puts a new constraint on deep submicrometer VLSI design.<>

Biopsies of skin from a 2-year-old heifer with spontaneously regressing dermal leukosis were examined. The heifer was not infected with bovine leukemia virus and was negative for tumor-associated antigens of enzootic bovine lymphosarcoma. By hematological standards for bovine leukemia, the heifer was positive at about 60 days post-occurrence of the disease (POD). At 53 days POD, lymphoblastic neoplastic cells in the dermis reacted with anti-T lymphocyte monoclonal antibody by the avidin biotin peroxidase complex method. The cells had intracytoplasmic clustered dense bodies under electron microscopy. From 53 to 83 days POD, figures of the transepithelial elimination (TE) against neoplastic cells and perivascular infiltration of small lymphocytes were in the dermis. Small lymphocytes reacted with anti-T lymphocyte monoclonal antibody. At necropsy there were no neoplastic lesions; there were flat lymph node-like tissues in the subcutis. Many germinal centers were seen in the lymphatic organs. Blood lymphocytes at 46 days POD were stimulated by phytohemagglutinin-P and concanavalin A. Sera, taken until 75 days POD and at necropsy, showed an inhibitory effect on mitogen-induced blastogenesis of normal bovine lymphocytes. These result suggested the existence of a spontaneous regressive mechanism against neoplastic lesions by TE and tumor immunity.

Summary The complete nucleotide sequence of the genome of a rakkyo strain of tobacco mosaic virus (TMV-R), which exhibits distinct host range differences from the common strain of TMV, was determined. The overall nucleotide sequence homology with TMV-U1 (a common strain of TMV) is 94.2%. The amino acid sequence homologies of the four encoded proteins (180K, 130K, 30K, coat protein) are from 95.9% to 98.0% compared with TMV-U1. To facilitate the analysis of the novel host range of TMV-R, a full-length clone of the genome containing a bacteriophage T7 RNA polymerase promoter was assembled from two cDNA clones and designated pRF3. In vitro transcripts derived from pRF3 were highly infectious. The infections of RF3, wild-type TMV-R, and U3/12-4 (derived from pU3/12-4, an infectious clone of TMV-U1) were compared onNicotiana tabacum cv. Bright Yellow (BY) plants. No systemic mosaic symptoms were observed on plants inoculated with RF3 and TMV-R, while BY plants inoculated with U3/12-4 developed distinct mosaic symptoms on the upper leaves 8–9 days post-inoculation. The green fluorescent protein (GFP) gene was introduced into pRF3 and pU3/12-4 by replacing the coat protein gene to get two GFP expressing chimeric virus clones: pR-GFP or pU1-GFP. Transcripts from pU1-GFP produced strong fluorescence when inoculated onto BY leaves, while those from pR-GFP produced only very faint fluorescence.

The complete nucleotide sequence of the RNA genome of turnip mosaic virus Japanese strain (TuMV-J) has been determined from five overlapping cDNA clones and by direct sequencing of viral RNA. The RNA sequence was 9833 nucleotides in length, excluding a 3′ terminal poly(A) tail. An AUG triplet at position 130–132 was assigned as the initiation codon for the translation of the genome size viral polyprotein which would consist of 3164 amino acid residues. Interestingly, a different amino acid sequence (continuous twenty amino acids) within the cytoplasmic inclusion protein between TuMV-J and Canadian strain of TuMV was observed, caused by an insertion and a deletion of nucleotides.

A 63-year-old man with malignant histiocytosis of the intestine died 3 days after gastrectomy for early gastric adenocarcinoma. Malignant histiocytosis of the intestine was unexpectedly found at autopsy. The intestine was thickened with mucosal erosions. Histologically, a few atypical large histiocyte-like cells were found in focal aggregates in the mucosa. These large cells expressed the T-cell antigen and monoclonality was demonstrated by the polymerase chain reaction showing variable-joining segment rearrangement in the T-cell receptor delta-chain gene. Malignant histiocytosis of the intestine was thus diagnosed.