Hiroki Kajihara

Aggressive natural killer cell leukaemia/lymphoma: report of four cases and review of the literature POSSIBLE EXISTENCE OF A NEW CLINICAL ENTITY ORIGINATING FROM THE THIRD LINEAGE OF LYMPHOID CELLS

The morphologic, immunologic, genotypic and functional properties of peripheral blood and bone marrow cells or cultured cells from four patients with a clinically aggressive non‐T, non‐B natural killer cell leukaemia/lymphoma (ANKL/L) are described. The leukaemic cells possessed medium to large granules in the cytoplasm, antigens against CD38, CD2, OKIa1 and NKH‐1 (CD56) monoclonal antibodies on their cell‐surface, and also showed natural killer (NK) activity. In addition, these ANKL/L belonged to neither T‐ nor B‐cell lineage, proved by studying clonal gene rearrangement for the Tβ, Tγ and Tδ receptors, and immunoglobulin.

Activated astrocytes with glycogen accumulation in ischemic penumbra during the early stage of brain infarction: immunohistochemical and electron microscopic studies

Brain infarction was induced in rats by injection of microspheres through the right internal carotid artery, and structural changes in the astrocytes were observed during the early period following the infarction. Necrotic foci, varying in size and shape, were found in the right hemisphere. After immunohistochemical staining for GFAP, GFAP-positive astrocytes in the perinecrotic area known as the ischemic penumbra had distinctly increased in number and size with elongation of cytoplasmic processes 3 days after infarction. Electron microscopic observation revealed that glycogen granules had markedly accumulated in the cytoplasm of astrocytes located in the ischemic penumbra 3 and 5 days after infarction. Seven days after infarction, however, the glycogen granules disappeared from the astrocytes. Intermediate filaments increasingly appeared in the protoplasmic astrocytes after 3 days and were abundant in the activated and hypertrophied astrocytes after 7 days. As a result of our present study, we conclude that: (1) the function of glucose uptake from blood vessels was not impaired in the astrocytes under hypoxic conditions; (2) the astrocytes actively ingested blood glucose through the endothelial cells and accumulated it as glycogen for activation of their functions, and the cell volume increased under hypoxic conditions; (3) the depression of energy metabolism and the decrease in the uptake of energy sources in the nerve cells promoted glycogen accumulation in the astrocytes under hypoxic conditions; (4) intermediate filaments (GFAP filaments) increased in number, coincident with the activation and enlargement of the astrocytes; and (5) protoplasmic astrocytes were transformed into fibrous astrocytes in the ischemic penumbra of the brain infarction.

Aggressive Natural Killer Cell Leukemia/Lymphoma with N901-Positive:Surface Phenotype: Evidence for the Existence of a Third Lineage in Lymphoid Cells

The morphology, immunologic and functional properties of peripheral blood and bone marrow cells or cultured cells from 2 patients with clinically aggressive non-T, non-B lymphoma/leukemia are described. The leukemic cells possessed medium to large granules in the cytoplasm, antigens against CD38, CD2, CD25, OKIa1, CD16, TA-1, CD9, CD24 and NKH-1 (N901) monoclonal antibodies on their cell surface, and also showed a high natural killer (NK) activity. Phenotypically, the cells in these disorders were quite different from T gamma leukemia cells bearing Fc receptor or the traditionally reported NK leukemia cells possessing HNK-1 (Leu 7) antigens on their surface. In addition, these leukemias/lymphomas belonged to neither T- nor B-cell lineage, proved by studying clonal gene rearrangement for the T beta and T gamma receptor, and immunoglobulin. Hence, a quite interesting and important point, as suggested by our data, is that all our cases expressed an antigen for NKH-1 (N901), which is detectable on all NK cell surfaces and they lacked the antigen for Leu 7 (HNK-1), which is usually detected on the surface of leukemic NK cells. These facts indicate that we are dealing with a leukemic NK cell subset which is quite different from cells of all other reported cases of NK cell leukemias. We therefore concluded that such disorders with an aggressive clinical nature and a poor prognosis as in our cases belong to a new clinical entity originating from a portion of the NK cell subset.(ABSTRACT TRUNCATED AT 250 WORDS)

Flow cytometric analysis of peroxidase negative acute leukemias by monoclonal antibodies—II. Acute megakaryoblastic and acute promegakaryocytic leukemias

Abstract In this report, we have described three cases of acute megakaryoblastic leukemia (AMKL) which were demonstrated by the presence of megakaryocyte-platelet-related cell-surface antigens detected by utilizing flow cytometry and monoclonal antibodies in addition to both PPO activity which was shown by ultrastructural cytochemistry and emergence of differentiation antigens while culturing these leukemic cells. The blasts of one case possessed both platelet GpIb and GpIIb/IIIa cell-surface antigens detected by 5F1 (CD36), AN51 (CDw42), and J15, P2 and HPL2 (CDw41), respectively, whereas the remaining two cases almost completely lacked Gplb cell-surface antigen. Hence, the former was diagnosed as immature (pro) megakaryocytic leukemia and the latter as AMKL from the viewpoint of immunophenotypic analysis as discussed in this article.

Electron microscopic observations of hypertrophied myocardium of rat produced by injection of monocrotaline.

The right ventricular myocardium of the cor pulmonare in the rat induced by subcutaneous single injection of monocrotallne has been studied by electron microscope. The hypertrophy and wearing of myocardium was sequentially categorized into (1) preparatory stage, (2) hypertrophied stage, and (3) damaged stage.

Analysis of peroxidase-negative acute unclassifiable leukemias by monoclonal antibodies. 1. Acute myelogenous leukemia and acute myelomonocytic leukemia

In this study, pretreatment peripheral and/or bone marrow blasts from 12 patients with acute unclassifiable leukemia (AUL) expressing the myeloid‐related cell‐surface antigen (CD 11) were isolated for further analysis. Despite a lack of myeloperoxidase (MPO) activity, 1 patients blasts contained cytoplasmic Auer rods. The circulating blasts from another patient expressed MPO while maintaining the same surface phenotype during 20 months of clinical follow‐up. In addition, the blasts from 3 cases demonstrated both myelomonocytic and monocyte‐specific surface antigens, whereas the remaining 9 cases completely lacked any monocyte‐specific antigen detectable by monoclonal antibodies, Mo2, My4 and Leu M3 (CD 14). The first case eventually was diagnosed as acute myelomonocytic leukemia and the second as acute myelogenous leukemia by means of immunophenotypic analysis using flow cytometry (FACS IV). In addition, the presence of MPO protein was identified in the cytoplasm of blast cells from 5 patients with AUL by means of a cytoplasmic immunofluorescence test using a monoclonal antibody (MA1). Our study indicates that non‐T, non‐B AUL expressing OKM1 (CD 11) antigens include acute leukemias which are unequivocally identifiable as being of either myeloid or myelomonocytic origin. However, further investigations, including immunophenotypic and cytoplasmic analysis, ultrastructural cytochemistry and gene analysis with molecular probes (tests applicable to normal myeloid cells), are necessary in order to determine the actual origin of blasts and to recognize the differentiation stages of the various types of leukemic cells from patients with undifferentiated forms of leukemia.

Eosinophilic coronary periarteritis (vasospastic angina and sudden death), a new type of coronary arteritis: report of seven autopsy cases and a review of the literature

A previously reported autopsy case of eosinophilic coronary periarteritis (ECPA, or isolated eosinophilic coronary periarteritis, IECPA), and an additional six autopsy cases of ECPA are reported. In addition, another four autopsy cases of ECPA reported in the literature are discussed. Fifteen cases of ECPA with spontaneous coronary dissection (hematoma), which appeared in the literature from 1987 to 2011, are also reviewed. The characteristic clinico-pathological findings of ECPA are: (a) variant angina (Prinzmetal’s vasospastic angina) appeared mainly from evening to early in the morning; (b) allergy or allergic history could be identified in only three of a total of 11 cases; (c) sudden unexpected death (sudden cardiac death) usually occurred early in the morning; (d) eosinophilic inflammation limited to the adventitia and periadventitial soft issue appeared in the epicardial large coronary arteries, chiefly in the left coronary anterior descending artery; (e) fibrinoid necrosis or granuloma could not be found in or around the inflammatory area; (f) no type of vasculitis could be found in any other tissues or organs (i.e., localized and non-systemic periarteritis); (g) ECPA was frequently accompanied by spontaneous coronary arterial dissection (SCAD) in the affected wall; and (h) ECPA without SCAD appeared mainly in men (male/female ratio was 8:3), while EPCA with SCAD appeared in almost all female cases (male/female ratio was 1:14). Although the etiology and pathogenesis are still unknown, we believe that ECPA (with or without SCAD) might be a distinct new type of coronary arteritis.

Argyrophil cells in early gastric carcinoma: an immunohistochemical and ultrastructural study.

SummaryEighteen argyrophil cell carcinomas in 101 early gastric carcinomas were examined histologically, ultrastructurally, and immunohistochemically for polypeptides, carcinoembryonic antigen (CEA), lysozyme, and human chorionic gonadotrophin (hCG). Seven of these 18 tumors had gastrin, and two of seven tumors also contained somatostatin. In all of these 18 tumors CEA were demonstrated. Seven had lysozyme and five of seven tumors also contained gastrin; hCG were present in four of 18 tumors and two of four tumors had gastrin, CEA, mucin, and lysozyme simultaneously. Argentaffin cells were found in seven of 18 tumors. Of the above seven tumors containing gastrin, three had argentaffin cells. Ultrastructurally, several types of secretory granules were noted and tumor cells resembling D1-or P cells were present in nine of the 18 tumors. Macroscopically, many of the tumors showed IIc or IIc+III type. Histologically, the 18 tumors consisted of six well differentiated adenocarcinomas and 12 poorly differentiated adenocarcinomas including signet-ring cell carcinoma. These 12 tumors frequently developed in the stomach of young females. In view of our previous investigations, it was suggested that the IIc-type argyrophil cell carcinoma histologically showing poorly differentiated adenocarcinoma may be related to scirrhous carcinoma of the stomach.Zusammenfassung18 Argyrophilzellencarcinome aus insgesamt 101 Frühcarcinomen des Magens wurden lichtmikroskopisch, elektronenmikroskopisch sowie immunhistochemisch mit Antiseren gegen Polypeptide, CEA, Lysozyme und hCG untersucht. 7 dieser Tumoren enthielten Gastrin und 2 unter ihnen außerdem Somatostatin. In allen 18 Tumoren wurde CEA nachgewiesen, 7 von diesen 18 Tumoren zeigten Lysozyme, darunter 5 auch noch Gastrin. In 4 Tumoren wurde hCG beobachtet, und in 2 aus dieser Reihe von 4 fand sich gleichzeitig Gastrin, CEA, Mucin sowie Lysozyme. Argentaffine Zellen wurden in 7 von 18 Tumoren beobachtet. Drei von 7 Gastrin enthaltende Tumoren hatten mehr oder weniger argentaffine Zellen. Elektronmikroskopisch wurden unterschiedliche Sekretgranula beobachtet und 9 von 18 Tumoren waren D1 oder P Zellen ähnlich. Makroskopisch entsprach die Mehrzahl der Tumoren dem IIc oder IIc+III Typ. Histologisch waren von diesen 18 Tumoren 6 gut differenzierte und 12 wenig differenzierte Adenocarcinome, einschließlich Siegelring-zellencarcinomen. Sie waren öfters im Fundusbereich jüngerer Frauen lokalisiert. Unter Heranziehung unserer schon publizierten Untersuchungsbefunde wird vermutet, daß IIc-Typ Argyrophilzellencarcinome mit dem histologischen Bild des wenig differenzierten Adenocarcinoms dem scirrhösen Carcinom zugeordnet werden kann.

Impairment of splenic B and T lymphocytes in the early period after severe thermal injury: immunohistochemical and electron microscopic analysis

Immunocompetent cells, such as lymphocytes and macrophages are easily damaged after severe thermal injury. In the present study, we investigated structural changes in splenic lymphocytes in the early period after a full skin thickness burn of 30% of the body surface area in rats. At 2h after thermal injury, numerous B lymphocytes had accumulated in the markedly expanded marginal zone of the splenic white pulp. Electron microscopy showed a small number of apoptotic cells in the marginal zone of the white pulp. After 5h, B lymphocytes in the marginal zone as well as in the lymphoid sheath and follicles were markedly decreased in number with an increase of tingible bodies and tingible body macrophages. The number of apoptotic cells had increased not only in the marginal zone, but also in the lymphoid sheath and follicles. After 12h, the splenic white pulp became atrophic with the appearance of a small number of large blastic cells and mitotic figures. After 24h, the splenic white pulp was still atrophic with a decrease in the number of lymphocytes, especially B lymphocytes. On the other hand, the large blastic cells and mitotic figures increased in number. Apoptotic cells decreased in number in the white pulp. After 48h, the lymph follicles were slightly enlarged and a small germinal centre occasionally appeared. A small number of T lymphocytes were observed in the splenic white pulp of the normal rats. However, the T lymphocytes almost disappeared shortly after thermal injury. A recovery in T cell number was observed only after 48h. These findings indicate that severe impairment of both B and T lymphocytes, circulating and in the lymphoid organs, occurs shortly after thermal injury and continues for several days. This severe damage to the lymphocytes is considered to be closely related to severe immune suppression after thermal injury.

Periarteritis of coronary arteries with severe eosinophilic infiltration. A new pathologic entity (eosinophilic periarteritis)

A 40 year-old male presented symptoms of angina pectoris for about nine years and expired with symptoms of unstable angina, changing pattern at the terminal stage. At autopsy, both right and left coronary arteries of the subepicardial region were grayish white and elastic hard. Histologically, inflammatory infiltration was localized in adventitia of coronary arteries located in the subepicardial region. Inflammatory cells infiltrated into the adventitia were mostly eosinophiles. The medial smooth muscle cells were well preserved and the intima showed irregular thickening with fibrosis. Vascular obstruction or recanalization could not be observed. As a result of these findings, it was considered that these inflammatory changes of the coronary arteries could be termed eosinophilic periarteritis. These inflammatory changes could not be found in the intramural coronary arteries. Rather extensive fibrosis could be seen in the muscle layer centering about the posterior wall of the left ventricle. No findings of angiitis could be detected in the blood vessels except subepicardial coronary arteries.