Hiroko Kuwabara

Small cell carcinoma of the gall-bladder with intestinal metaplastic epithelium.

A case of small cell carcinoma of the gall‐bladder Is described. lmmunohistochemically, the tumor cells were positive for chromogranin A, synaptophysin and neuronspecific enolase, which suggests that they derived from neuroendocrine cells. The overlying and surroundlng epithelium of the tumor showed intestinal metaplasia including goblet cells, pseudopyloric glands, Paneths cells, and chromogranin A and synaptophysin‐positive endocrine cells. Definite adenocarcinoma was absent. The endocrine cells in the epithellum were more numerous In the vicinity of the tumor. The present case supports the supposition that endocrine cell tumor (including small cell carcinoma) of the gall‐bladder may develop from endocrine cells of the intestinal metaplastic lesion.

Specific skin manifestations in CD56 positive acute myeloid leukemia

We found 16 CD56+ cases (29.6%) among 54 acute myeloid leukemia (AML) patients; they showed significantly Frequent cutaneous involvement compared to CD56‐ cases (43.8% vs.15.8%, p<0.05). Four of the CD56+ AML cases with specific skin manifestations were reviewed histologieally. In all cases, cutaneous leukemic cells were seen in the dermis and subcutaneous tissue with accentuation around the adnexa/nerve, but sparing the epidermis. In addition, angiocentric/angiodestructive and prominent cohesive tumor cell growth were seen in two rases, respectively. These findings suggest that the expression of CD56 may often be associated with the cutaneous involvement in AML, and that the above histological findings should remind us of the possibility of specific skin manifestations in CD56+ AML.

Immunohistochemical adrenomedullin expression is decreased in the placenta from pregnancies with pre-eclampsia.

The purpose of the present study was to investigate whether placental immunohistochemical adrenomedullin expression in normal normotensive pregnancies is different from that in pregnancies with pre‐eclampsia. Placental tissues were obtained from seven normal normotensive pregnancies and 12 pregnancies with pre‐eclampsia. The intensity of adrenomedullin staining in syncytiotrophoblasts was evaluated by means of immunohistochemistry and the ratio of the number of intact tertiary villi to that of total tertiary villi (intact/total villi ratio) was determined. The intensity of adrenomedullin expression in the placenta obtained from pregnancies with pre‐eclampsia was significantly decreased compared with expression in placentas from uncomplicated normotensive pregnancies (P< 0.005). The intact/total villi ratio in placentas obtained from pregnancies with pre‐eclampsia was significantly lower than that in placentas from normal normotensive pregnancies (P< 0.0001). In the amnion and extravillous trophoblast cells in both groups, no difference for the intensity of adrenomedullin expression was noted. These results suggest that adrenomedullin synthesis in the villous syncytiotrophoblasts is decreased in pregnancies with pre‐eclampsia.

Ciliary beat frequency controlled by oestradiol and progesterone during ovarian cycle in guinea‐pig Fallopian tube

The ciliary beat frequency (CBF) of guinea‐pig fimbria during the ovarian cycle was measured by video microscopy using a high‐speed camera (500 Hz). In the follicular phase, with increasing concentrations of β‐oestradiol ([βE2]) and a low concentration of progesterone ([PRG]), CBF increased from 13.5 to 16 Hz. In the ovulatory phase, with further increase of [βE2], CBF decreased gradually from 16 to 13.5 Hz. In the early luteal phase, with low [PRG] and [βE2], CBF increased to ∼17 Hz; however, in the middle luteal phase, with increasing [PRG], CBF decreased (∼12 Hz), and in the late luteal phase, with decreasing [PRG], CBF increased to ∼15 Hz. Then, in the resting phase, with low [βE2] and [PRG], CBF decreased immediately to ∼14 Hz. The CBF of the fimbria was measured in guinea‐pigs treated with β‐oestradiol benzoate (βE2B) or medroxyprogesterone (mPRG). A low dose of βE2B increased CBF to ∼14.5 Hz, whereas a high dose decreased it to ∼11 Hz. A βE2 receptor blocker, ICI‐182,780, abolished the βE2B‐induced CBF changes and maintained CBF at ∼12.0 Hz. Medroxyprogesterone decreased CBF to ∼12.5 Hz, and mifepristone (a PRG receptor blocker) abolished the mPRG‐induced CBF decrease and maintained CBF at ∼15 Hz. The addition of both blockers increased CBF to ∼18 Hz, suggesting that activation of βE2 or PRG receptors decreases the CBF of the fimbria. In conclusion, a moderate [βE2] increase maintains a high CBF (15.5 Hz) in the follicular phase, and then further [βE2] increase decreases CBF to 13.5 Hz in the ovulatory phase. In the early and late luteal phase, low [βE2] and [PRG] increase CBF to 17 and 15 Hz, respectively, and in the middle luteal phase a high [PRG] decreases CBF (to ∼12 Hz). Thus, the CBF of the fimbria was controlled by signals via βE2 and PRG receptors in guinea‐pigs.

Prepro-orexin mRNA expression in the rat brain is increased during pregnancy

The purpose of this study was to investigate whether orexin expression in the rat brain was changed during pregnancy. Brain samples were obtained from 5 nonpregnant rats and 10 pregnant rats (5; day 10 of gestation, and 5; day 20 of gestation). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed to investigate the expression of prepro-orexin mRNA and the housekeeping gene in the rat brain. The signals were quantified by the densitometric analysis. The distribution and expression of orexin-A and orexin-B were determined using immunohistochemistry. The ratio of the prepro-orexin mRNA expressions to the housekeeping gene expression in pregnant rat brain were significantly higher than that in nonpregnant control. There was no significant difference between prepro-orexin mRNA levels of day 10 and day 20 of gestation. Immunohistochemical staining for orexin-A and orexin-B was present in neurons within and around the lateral and posterior hypothalamic areas in both nonpregnant and pregnant rats. These results suggest that increased prepro-orexin mRNA levels at early gestational age in the maternal rat has a role on energy metabolism during pregnancy.

Inflammation as well as angiogenesis may participate in the pathophysiology of brain radiation necrosis

Radiation necrosis (RN) after intensive radiation therapy is a serious problem. Using human RN specimens, we recently proved that leaky angiogenesis is a major cause of brain edema in RN. In the present study, we investigated the same specimens to speculate on inflammations effect on the pathophysiology of RN. Surgical specimens of symptomatic RN in the brain were retrospectively reviewed by histological and immunohistochemical analyses using hematoxylin and eosin (H&E) staining as well as immunohistochemical staining for VEGF, HIF-1α, CXCL12, CXCR4, GFAP, CD68, hGLUT5, CD45, IL-1α, IL-6 TNF-α and NF-kB. H&E staining demonstrated marked angiogenesis and cell infiltration in the perinecrotic area. The most prominent vasculature was identified as thin-walled leaky angiogenesis, i.e. telangiectasis surrounded by prominent interstitial edema. Two major cell phenotypes infiltrated the perinecrotic area: GFAP-positive reactive astrocytes and CD68/hGLUT5-positive cells (mainly microglias). Immunohistochemistry revealed that CD68/hGLUT5-positive cells and GFAP-positive cells expressed HIF-1α and VEGF, respectively. GFAP-positive cells expressed chemokine CXCL12, and CD68/hGLUT5-positive cells expressed receptor CXCR4. The CD68/hGLUT5-positive cells expressed pro-inflammatory cytokines IL-1α, IL-6 and TNF-α in the perinecrotic area. VEGF caused leaky angiogenesis followed by perilesional edema in RN. GFAP-positive cells expressing CXCL12 might attract CXCR4-expressing CD68/hGLUT5-positive cells into the perinecrotic area. These accumulated CD68/hGLUT5-positive cells expressing pro-inflammatory cytokines seemed to aggravate the RN edema. Both angiogenesis and inflammation might be caused by the regulation of HIF-1α, which is well known as a transactivator of VEGF and of the CXCL12/CXCR4 chemokine axis.

Alterations of p53 and Rb genes in a novel human GM-CSF-dependent myeloid cell line (OHN-GM) established from therapy-related leukaemia

A novel GM‐CSF‐dependent myeloid cell line, OHN‐GM, was established from a patient who developed acute myelogenous leukaemia (AML) as a consequence of myelodysplastic syndrome (MDS). As the patient had previously received cytotoxic chemotherapy for Hodgkins disease, the MDS and AML were probably related to such therapy. Sequential karyotypic analysis established a del(5q) as the initial cytogenetic abnormality. Additional alterations, including t(10;13)(q24;q14), had developed subsequently during disease progression. Southern blot analysis of OHN‐GM cells suggested deletion of one allele of the IRF‐1 gene, although no aberrant transcripts were detected. Fluorescence in situ hybridization analysis revealed the deletion of the Rb gene due to the t(10;13)(q24;q14) translocation, and Western blot analysis demonstrated the absence of Rb protein in OHN‐GM cells. Finally, the OHN‐GM cells exhibited two missense point mutations in highly conserved regions of the p53 gene. These observations suggest that a multistep process, involving alterations of Rb and p53 genes, may have contributed to the patients disease development and progression. To our knowledge, OHN‐GM is the first cell line derived from a therapy‐related AML. These cells may aid the investigation of leukaemogenesis as well as the biology of secondary leukaemia.

Secondary myeloid/natural killer cell precursor acute leukemia following essential thrombocythemia

The de novo leukemic transformation of essential thrombocythemia is a rare event, and usually associated with previous treatments. We describe a patient who received treatments with nitrosourea for long-standing essential thrombocythemia and subsequently developed extramedullary tumors, tentatively diagnosed as lymphoblastic lymphoma. Combination chemotherapy was initially successful, but relapsed with marked bone marrow involvement. Surface marker analysis revealed that the tumor cells had CD5, CD7, CD33, CD34, and CD56 antigens but lacked other T-cell, and B-cell markers. Immunogenotypical studies revealed germline configurations for both T-cell receptors and immunoglobulin genes. These clinical and phenotypical features are consistent with a myeloid/natural killer cell precursor leukemia, a recently proposed distinct clinical entity. To our knowledge, this is the first report of secondary leukemia of myeloid/ natural killer cell precursor origin, and suggest that myeloid/natural killer cell precursor might be a potent target of therapy-related leukemia.

Pigmented squamous cell carcinoma of the alveolar ridge in the oral mucosa

The clinical and morphologic features of a pigmented squamous cell carcinoma of the alveolar ridge in an 81-year-old Japanese woman are reported. The tumor was typical, well-differentiated squamous cell carcinoma but had many melanin-containing cells within it. Electron microscopy showed melanosomes in macrophages, melanocytes, and neoplastic squamous cells. Those in the neoplastic squamous cells seemed to have been excreted from the cytoplasmic processes of melanocytes.

Pigmented Villonodular Synovitis (Giant Cell Tumor of the Synovium) Occurring in the Vertebral Column

A case of pigmented villonodular synovitis (giant cell tumor of the synovium) involving the vertebral column is presented. The tumor grew outside the dura and extended to the paravertebral connective tissue, causing sensory and motor disturbance indicative of spinal cord compression. This anatomic location is very rare for lesions of this type, and to our knowledge, this case is only the fifth reported in the English language literature.