Variability in cholesteryl ester transfer protein in healthy Japanese hyper-HDL-cholesterolemic subjects

OBJECTIVE: Hyper-high density lipoprotein (HDL)-cholesterolemia has been considered to be anti-atherogenic and is referred to as longevity syndrome. However, hyper-HDL-cholesterolemia induced by a cholesteryl ester transfer protein (CETP) deficiency may not be athero-protective, rather being atherogenic in nature. In a rural area in central Japan, the incidence of hyper-HDL-cholesterolemia has been found to be rather high (3.1% of healthy people). We studied healthy Japanese people in this area with hyper-HDL-cholesterolemia, particularly in relation to CETP. METHODS: Serum lipids were analyzed, and CETP mass was determined with an enzyme immunoassay method. MATERIALS: Blood was drawn after an overnight fast from 17 Japanese (5 males and 12 females) with serum HDL-cholesterol (C) > or =100 mg/dl. RESULTS: Serum CETP mass in hyper-HDL-cholesterolemic subjects was distributed in a wide range. Serum CETP mass was positively correlated with low-density lipoprotein (LDL)-C, apolipoprotein (Apo) B, and LDL-C/HDL-C, with statistical significance. CETP was also positively correlated with LDL-C/Apo B. CONCLUSION: These results suggest that hyper-HDL-cholesterolemia may not be a single clinical entity, but a mixture of various pathophysiological conditions, and that the ratio of LDL-C to HDL-C and the size of LDL may be important factors in classifying these conditions.     

Naloxone-precipitated morphine withdrawal elicits increases in c-fos mRNA expression in restricted regions of the infant rat brain

This paper is the first report of a genetic index for morphine withdrawal in infant rats. We examined the effects of naloxone (2 mg/kg) on c-fos mRNA levels in brains of infant and adult rats following repeated treatment with morphine (20 mg/kg, once daily for 5 days). One hour after a single administration of naloxone (naloxone challenge), an increase in c-fos mRNA was observed in the olfactory bulb, hypothalamus and medulla oblongata of infant rats, and in the olfactory bulb and hypothalamus, but not in the medulla oblongata of adult rats. The c-fos mRNA levels returned to control levels 6 h after the naloxone challenge. The increase in c-fos mRNA levels was followed by body weight loss in both infant and adult rats. When MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, was co-administered along with morphine, it inhibited the naloxone-induced increases in c-fos mRNA levels in infant rats following repeated morphine administration. These results suggest that physical dependence develops in infant rats following repeated morphine administration and that the increment of c-fos mRNA levels is a useful indicator for naloxone-precipitated morphine withdrawal in infant as well as in adult rats.     

7,12-DMBA-induced rat leukemia: a review with insights into future research

7,12-Dimethylbenz[a]anthracene (DMBA) elicits leukemia in Long–Evans rats (LE). This leukemia is mostly erythroblastic and 30% of leukemias have total and partial trisomy of #2 chromosome and the rest have diploid karyotype. The common duplication site is in 2q26–q34 and N-ras gene is located in 2q34. 7,8,12-Trimethylbenz[a]anthracene (TMBA) also induces similar leukemias. These leukemias reveal a highly specific mutation of N-ras gene as in human leukemias. N-ras mutation is induced 48 h after DMBA treatment. Wild type N-ras allele is frequently lost in diploid leukemias but not in trisomy type. Therefore, a gene dosage problem related to the mutant N-ras gene is involved in development of leukemia. Some secondary genetic rearrangements involving abl and H-ras are also observed in cultured leukemia cells. DMBA-induced chromosome aberrations as well as leukemia are enhanced by erythropoietin and blocked by Sudan III given prior to DMBA treatment. This leukemia will provide an important tool for chemical carcinogenesis and leukemia studies.     

Myelofibrosis Developing in Megakaryoblastic Leukemia in a Boy with Down's Syndrome

A 2 1 /2-year-old boy with Down's syndrome developed pancytopenia. After spontaneous recovery, leukocytosis with blast cells in peripheral blood and bone marrow developed, and it was associated with thrombocytopenia and splenomegaly. After transient but complete disappearance of all of these findings, they reappeared and a marked fluctuation with 4 subsequent peaks of leukocytosis was observed. Splenomegaly appeared in association with eukocytosis in early phase and persisted after the third peak. Blast cells were identified as megakaryoblasts and had a karyotype of 47, XY, -7, -1 2, +21, +der(7)t(7p+;?)(p22;?), +der(12)t(6;12p+)(pll;ll). Bone marrow biopsy at the time of recovery from pancytopenia showed hypercellularity with many megakaryocytes and minimal fibrosis. Subsequent serial bone marrow biopsies showed progressively developing fibrosis leading to the final picture of typical myelofibrosis. A histological examination of spleen and an omental tissue showed marked blastic infiltration associated with megakaryocytic infiltration. This case suggests that megakaryoblastic leukemia associated with myelofibrosis is anadditional type of abnormal myelopoiesis seen in Down's syndrome.     

A case of anal fistula cancer probably developing from intraluminal dissemination of rectal cancer

A 63-year-old man with a history of anal fistula was admitted to our hospital because the anal pain didn't disappear after the operation. On digital examination, a hard mass measuring 3.0 cm in diameter was found at the anal canal. Biopsy of the mass showed moderately differentiated adenocarcinoma. Colonoscopy revealed another rectal cancer at 15 cm from anal verge. Biopsy of the tumor also showed moderately differentiated adenocarcinoma, resembling the anal canal tumor. Because the histological findings of both tumors were nearly identical, we considered that cancer cells from the rectal cancer had been implanted and developed the metastatic tumor in the anal fistula. The patient underwent anterior resection for the rectal cancer, and a local resection for the anal canal cancer. Immunohistochemical staining for Ki-67, p53, Muc2, CD10, CK-7, and CK-20 revealed similar patterns in both tumors. Additionally, genetic analysis for p53, K-ras, and MSI revealed similar patterns in both tumors. We may suggest from these results that cancer cells from the rectal cancer had been implanted and developed the metastatic tumor in the anal canal.     

Bone metastasis of intracranial meningeal hemangiopericytoma

The authors investigated the clinical and radiological features and the treatment strategy for bone metastasis from a rare tumor, intracranial meningeal hemangiopericytoma. The clinical presentations and characteristic imagings were retrospectively reviewed in 15 bony metastatic lesions of four patients with this tumor. All four cases were initially diagnosed as atypical meningioma, and all of the bone metastases developed more than 10 years after the initial intracranial surgery. The common symptom induced by the metastatic lesions was pain. On plain roentgen films and computed tomography (CT), the involved bones showed thinning and expansion. On bone scintigraphy, a “cold-in-hot” appearance was typically observed. The clinical and radiological findings were diagnosed as bone metastasis from intracranial meningeal hemangiopericytoma. The prognosis after bone metastasis was relatively short compared to the long duration before bone metastases, because of the coexistence of other, visceral, metastasis. Combined with effective radiation therapy, surgical intervention for bone metastasis of this tumor should be carefully considered.     

Ameloblastoma induces osteoclastogenesis: a possible role of ameloblastoma in expanding in the bone

Ameloblastoma, a tumor located in bone, when neglected, can perforate the bone and, ultimately, spread into the soft tissues. To expand in the bone, ameloblastoma must have a mechanism of resorbing the surrounding bone. However, the mechanism for bone resorption is poorly understood. In the present study, we found that RANKL and TNFalpha were expressed and secreted by ameloblastoma cells, and was proven to induce osteoclastogenesis. Our present results also showed that phosphorylation of p38, SAPK, p44/42 and Akt were upregulated under treatment of 10xCM (concentrated conditioned media of AM-1 cells). We also noticed formation of resorption lacunae on dentin slice by 10xCM-induced osteoclast-like MNCs. These results suggested that ameloblastoma by secreting RANKL and TNFalpha could induce osteoclastogenesis.     

Dual Balloon-Occluded Retrograde Transvenous Obliteration of Gastric Varix Draining into the Left Adrenal Vein and Left Inferior Phrenic Vein

A 66-year-old woman with a gastric varix, draining into a dilated left adrenal vein and a left inferior phrenic vein, was treated with dual balloon-occluded retrograde transvenous obliteration (B-RTO). Under balloon occlusion of the left adrenal vein and the left inferior phrenic vein, retrograde injection of a sclerosant (5% ethanolamine oleate) into the gastric varix was performed. Two weeks later, disappearance of flow in the gastric varix was confirmed on endoscopic ultrasound examination.