A comparison of ultrastructural changes on endomyocardial biopsy specimens obtained from patients with diabetes mellitus with and without hypertension

Summary The pathogenesis of diabetic cardiomyopathy is unknown. The synergistic, or enhanced, effect of hypertension on pathological changes in the heart of diabetic patients has been highly suspected. The purpose of this study was to evaluate the myocardial changes related to diabetes mellitus with and without hypertension, using biopsy specimens. We examined the ultrastructural changes in biopsy specimens of the endomyocardium obtained from 25 patients. They were divided into four groups: controls without hypertension or diabetes mellitus (n=6), and patient with hypertension (n=3), diabetes mellitus (n=8), and diabetes with hypertension (n=8). The diabetic patients showed nearly normal or mildly depressed systolic left ventricular function. Ultrastructural pictures were analyzed for thickening of the capillary basement membrane, presence of toluidine blue-positive materials (i.e., materials showing metachromasia) in the myocytes, size of myocytes, and interstitial fibrosis. The thickening of the capillary basement membrane, the accumulation of toluidine blue-positive materials, and interstitial fibrosis were all significantly greater in the patients with diabetes mellitus compared to the control subjects. The myocytes tended to be small (cell atrophy) in the diabetes group. Although these pathological changes in the heart were characteristic of diabetic patients, irrespective of the presence or absence of hypertension, the presence of hypertension increased the pathological changes of myocardial cells as well as abnormality in the capillary vessels in patients with diabetes mellitus. Alterations in the myocardial cells and capillaries, caused by diabetes mellitus, may lead to myocardial cell injury and interstitial fibrosis and, ultimately, to ventricular systolic and diastolic dysfunction, especially when the diabetes is accompanied by hypertension.     

A case of ectopic large pituitary adenoma

Ectopic pituitary adenomas are very rare and only 17 cases have been reported. In this paper we present a case of large pituitary adenoma originating in the suprasellar region. A 26-year-old man was admitted to our clinic with a chief complaint of headaches. Neurological examination revealed slight disorientation and bilateral choked disk. Hormonal study revealed that the serum prolactin level was 3300ng/ml and serum growth hormone level was 29.5ng/ml. Computed tomography showed a large mass in the suprasellar region extending upward to the third ventricle and backward to the pons. T1-weighted MR imaging revealed that the intensity of the mass was the same as that of the cerebral cortex and the pituitary gland was showing high intensity in the pituitary fossa. The tumor was radically removed via the transpetrosal transtentorial approach. Histologically, the tumor was a prolactin-growth hormones producing pituitary adenoma. The literature was reviewed and the origin of the tumor was discussed.     

Recent Trends in the Treatment and Prognosis of Adult Leukemia with Characteristics of Patients in Japan: Transition during the Fifteen Years from 1971 to 1985

Patients with acute (2,569) and chronic (957) leukemia diagnosedat 19 institutes took part in the study on the "MultidisciplinaryTreatment of Leukemia" between 1971 and 1985 and were investigatedretrospectively. By dividing the 15 years into three five-yearperiods, we were able to compare patient ratios in the differentperiods. The proportions of acute to chronic leukemia casesshowed no obvious change; however, the proportions of casesdiagnosed as acute lymphocytic leukemia in acute leukemia showeda significant increase. The main chemotherapeutic drugs usedduring the three time periods were cytarabine or its analogues,the anthracyclines, 6-mercaputopurine and prednisolone, againstacute myelogenous leukemia, and the vinca alkaloids, prednisoloneand the anthracyclines against acute lymphocytic leukemia. Therate of complete remission from acute myelogenous leukemia mademarked progress, from 45.1% during 1971–1975 to 62.3%during 1981–1985, but that of acute lymphocytic leukemiashowed no significant progress, being 65% during 1971–1975and 69.7% during 1981–1985. The durations of remission,however, and the survival times for patients with acute lymphocyticleukemia, as well as for those with acute myelogenous leukemia,became significantly longer over the three periods. Median survivaltimes from chronic myelocytic leukemia were 37–40 mo inall three periods, showing no progress. There was a better prognosisin cases of chronic myelocytic leukemia with, than without,Philadelphia chromosome. Except for a low incidence of chroniclymphocytic leukemia in Japan, adult leukemia patients' characteristicsand prognoses seem to be almost the same in Japan as in theU.S.A. and Europe.     

Cell culture of clonal ginbuna crucian carp hematopoietic cells: differentiation of cultured cells into erythrocytes in vivo

We cultivated kidney hematopoietic cells from clonal triploid ginbuna crucian carp, Carassius auratus langsdorfii. Proliferating cells from hematopoietic cell cultures were harvested and injected into tetraploid hybrids (clonal triploid ginbuna and goldfish hybrid) which possess three sets of chromosomes from a triploid clone and a haploid set of chromosomes from goldfish (Carassius auratus). After injection of cultured triploid cells (donor cells), blood samples were obtained from tetraploid hybrids (recipients) every other week. Blood cells stained with acridine orange were measured by flow cytometry to trace the injected donor cells by means of differences in DNA content. Although erythrocytes were not produced in donor cell cultures, such cultures maintained precursor cells capable of differentiation into erythrocytes in vivo. After 4-12 weeks of transplantation, mature erythrocytes derived from the donors were observed in the blood circulation of the recipient fish. These results indicated that the ginbuna hematopoietic cell culture system is an in vivo situation suitable for the study of hematopoietic control mechanisms.     

Transcriptome analysis of hagfish leukocytes: a framework for understanding the immune system of jawless fishes

Jawless fishes occupy a critical phylogenetic position in understanding the origin of the adaptive immune system. Here, we performed large-scale expressed sequence tag analysis of leukocytes isolated from the inshore hagfish Eptatretus burgeri. Although we found many immunity-related genes such as those involved in lymphocyte or hematopoietic cell signaling and development as well as cytokine and cytokine receptor genes, MHC molecules or antigen receptors were not identified. We characterized two hagfish cDNAs that closely resembled mammalian proteins with essential roles in adaptive immunity, one encoding a GATA3-like molecule and another encoding a Bruton's tyrosine kinase (Btk)-like molecule. The GATA3-like gene of hagfish was equidistant from GATA3 and GATA2 in jawed vertebrates. Similarly, the hagfish Btk-like molecule was not Btk itself, but qualified as a pre-duplicated form of Btk and Bmx in jawed vertebrates. In total, our work provides circumstantial evidence that adaptive immunity is unique to jawed vertebrates.     

Immunogenetic analysis of gastric MALT lymphoma-like lesions induced by Helicobacter pylori infection in neonatally thymectomized mice

Most gastric mucosa-associated lymphoid tissue (MALT) lymphomas are caused by Helicobacter pylori (H. pylori) infection. We previously reported that acquired lymphoid follicles with germinal centers were induced by H. pylori infection in neonatally thymectomized (nTx) mice. In the present study, we developed gastric MALT lymphoma-like lesions in nTx mice by long-term H. pylori infection, and performed immunogenetic analyses. BALB/c mice were thymectomized on the 3rd day after birth. At 6 weeks of age, mice were orally infected with 10(8) H. pylori and serially killed 2, 4, 6, and 12 months later. Normal BALB/c and noninfected nTx mice served as controls. Follicle formation occurred after 2 months of H. pylori infection in the nTx mice. Follicle formation and infiltration of intraepithelial lymphocytes progressed in a time-dependent manner. Lymphoepithelial lesions, a characteristic feature of MALT lymphoma, also occurred in a time-dependent manner (100% at 12 months). Serum immunoelectrophoresis revealed a monoclonal band (M-protein) in 30% (3/10) of mice 6 months after infection. M-protein-positive mice had amplification of one or two IgM and/or IgG heavy-chain genes in the gastric B lymphocytes, as determined with polymerase chain reaction, suggesting mono- or oligoclonality. Overexpression of Bcl-X(L) protein was immunohistologically observed in the infiltrating B lymphocytes and in some follicular B lymphocytes in 80% (8/10) of the cases at 12 months. Thus, H. pylori infection is involved in the development of gastric MALT lymphoma-like lesions in nTx mice. Our mouse model is useful for clarifying the pathogenetic mechanism of gastric MALT lymphoma by H. pylori infection.     

Toll-like receptor 9 is expressed on follicle-associated epithelia containing M cells in swine Peyer's patches

The precise distribution and expression of Toll-like receptor (TLR) 9 in gut-associated lymphoid tissues (GALTs) has not been elucidated. In this study, we investigated the expression pattern of TLR9 in adult and neonatal swine GALTs by real-time quantitative PCR, western blot, confocal laser microscopy and flow cytometric analysis. The swine TLR9 gene was preferentially expressed in adult Peyer's patches (Pps) and mesenteric lymph nodes (MLNs), which contained approximately three times higher TLR9 than the spleen. Other tissues exhibited only weak expression of TLR9. In neonatal swine, elevated expression of TLR9 was detected only in MLNs. We firstly showed that highly expressive (TLR9(+)) cells were formed in Pps and MLNs. In addition, TLR9(+) cells were present not only in immune cells such as dendritic cells and B cells but also in follicle-associated epithelia (FAE) including membranous cells (M cells) in Pps. These results suggest that Pps and MLNs provide the host defense with the ability to respond to a variety of bioactive oligonucleotides (ODNs) from bacteria at a conductive site of initial immune responses.