Prevention by Methionine of Enhancement of Hepatocarcinogenesis by Coadministration of a Choline-deficient L-Amino Acid-defined Diet and Ethionine in Rats

The effects of methionine on hepatocarcinogenesis induced by Coadministration of a choline-deflcient L-amino acid-defined (CDAA) diet and ethionine were examined. F344 male rats were divided into 4 experimental groups. Groups 1 and 2 received the CDAA diet and a choline-supplemented L-amino acid-defined (CSAA) diet, respectively. Group 3 received the CDAA diet containing 0.05% ethionine, and group 4 the CDAA diet containing 0.05% ethionine and 0.47% methionine. Animals were killed after 12 weeks of treatment. Histologically, the CDAA diet induced intracellular fat accumulation and foci. In contrast, ethionine caused not only foci, but also hyperplastic nodules, cholangiofibrosis and the proliferation of oval cells without such fat accumulation. Methionine abolished the development of all of the liver lesions induced by Coadministration of the CDAA diet and ethionine. To investigate the effects of methionine on induction of c- myc and c-Ha- ras expression, as well as generation of 8-hydroxyguanine (8-OHGua) and 2-thiobarbituric acid-reacting substances (TBARS), by Coadministration of the CDAA diet and ethionine, subgroups of 3 to 5 animals were killed at 2, 4, 8 or 11 days after the beginning of the experiment. Coadministration of the CDAA diet and ethionine markedly enhanced the level of expression of c- myc and c-Ha- ras , 8-OHGua formation and TBARS generation as compared with the CDAA or CSAA diet within 11 days, and methionine blocked these actions. These results indicate that addition of methionine prevents the induction of c- myc and c-Ha- ras expression, 8-OHGua formation and TBARS generation, as well as hepatocellular lesions, by Coadministration of the CDAA diet and ethionine in rats, and suggest a possible involvement of oxidative stress and gene expression in hepatocarcinogenesis by these agents.     

Primary Non-Hodgkin Malignant Lymphoma of the Male Breast

A case of primary non-Hodgkin lymphoma of the male breast isreported. The patient was a 76-year-old Japanese with a historyof bilateral gynecomastia. After the patient had received sexhormone treatment for the gynecomastia, rapid growth of a tumorin the right breast was noted, with regression of a contralateralbreast lesion. Clinically, inflammatory breast cancer was suspected,and right mastectomy with ipsilateral axillary lymph node dissectionwas performed after intraarterial infusion chemotherapy usinga cis-platinum derivative. The histology of the surgical specimenwas non-Hodgkin malignant lymphoma of the diffuse large celltype, with focal tumor necrosis. Immunohistochemically, thetumor cells showed a B-cell nature. The patient is currentlywell without disease 39 months after surgery.     

Effects of growth hormone on testicular dysfunction induced by cyclophosphamide (CP) in GH-deficient rats

Growth hormone (GH) is known to accelerate spermatogenesis and maintain gonadal function. In this study, we evaluated the effect of GH on recovery from testicular damage induced by cyclophosphamide (CP). Eleven- to fourteen-week-old GH-deficient Lewis rats (dw/dw) were divided into 4 groups (n = 10 each), with one group serving as controls. In the CP group, CP was intravenously administered in daily doses of 50 mg/kg for 2 days, followed by daily doses of 10 mg/kg for the next 3 days. In the GH group, rat GH was subcutaneously administered at a daily dose of 0.3 mg/kg until the rats were sacrificed. In the CP/GH group, GH and CP administration were started simultaneously. In the CP/preGH group, GH administration was started 14 days before CP administration. Five rats from each group were sacrificed at days 14 and 28 after administration of CP. Spermatogenesis was then evaluated morphometrically by counting numbers of cells at several stages of the spermatogenic cycle. On day 14, there were no significant differences in the numbers of the spermatocytes between CP and CP/GH group. On day 28, the numbers of spermatocytes and motility of spermatozoa in CP/GH group were greater than those of CP group were. In the CP/preGH group, these effects of GH administration were not observed. These results suggested that administration of GH improved testicular function damaged by CP under GH-deficient condition, when GH and CP administration are started simultaneously.     

Atlas burst fracture (Jefferson fracture) requiring surgical treatment after conservative treatment--report of two cases

Most cases of atlas burst fracture do not require surgical stabilization, because they can be successfully treated with external immobilization. The authors present two cases of atlas burst fracture in which surgical stabilization was required after external immobilization. The first patient was a 50-year-old male and the second patient was a 34-year-old male. Both presented with neck pain without neurological symptoms after a traffic accident. Neuroradiological examinations revealed atlas burst fracture in both patients. They were initially treated with conservative treatment; one with a rigid collar and the other with a halo vest. However, lateral offset of the atlas on the axis increased and atlanto-axial instability became evident three months later in both patients. They underwent upper cervical arthrodesis with satisfactory results. The authors review surgical indication and its timing in patients with atlas burst fracture.     

The usefulness of 3D-CTA for the diagnosis of a ruptured aneurysm at the origin of the duplicated middle cerebral artery: case report

Duplication of the middle cerebral artery is known as a rare anomalous vessel arising from the internal carotid artery and an aneurysm at the origin of the duplicated middle cerebral artery is very rare. We presented a case of ruptured aneurysm at the origin of the duplicated middle cerebral artery and discussed the usefulness of 3D-CTA (three-dimensional computed tomographic angiography) for its diagnosis. A 34-year-old female suffered from severe headache and was admitted to our hospital. CT scan revealed diffuse subarachnoid hemorrhage and angiography revealed duplication of the right middle cerebral artery and dilatation at its origin. We could not identify it as an aneurysm by angiography, so we performed 3D-CTA. 3D-CTA was able to demonstrate clearly the aneurysm at the origin of the duplicated middle cerebral artery and we performed neck clipping of the ruptured aneurysm. To our knowledge, previously there have been only 14 cases which reported such an aneurysm at the origin of a duplicated middle cerebral artery. We reviewed the 15 cases including ours and found that, in 4 cases, the aneurysm could not be detected by the initial angiography. We suspected that most of these aneurysms were small, so the detection of the aneurysms by angiography was difficult. We conclude that 3D-CTA is useful for diagnosing aneurysms at the origin of the duplicated middle cerebral artery even when thy can't be detected by angiography.     

Anti-osteopenic effect of taurine: possible involvement of activated MEK-ERK-Cbfa1 signaling

Previously we first noted that taurine (TR) has anti-osteopenic effect on low Ca diet-induced osteopenia in rats (1). Employing osteoblastic MC3T3-E1 cells, the mechanism of the anti-osteopenic effect was explored in vitro. TR (1 mM) was found to promote mineralization of extracellular matrices, without affecting alkaline phosphataase activity. Gel shift assay using 32P-labeled OSE2 (osteoblast-specific cis-element 2: the consensus sequence for Cbfa1, refer to 2) indicated that TR (1 mM) increased the nuclear localization of Cbfa1, just as TPH (1-34) (3,4) and bisphosphonates did (5). In addition, TR was found to stimulate ERK phosphorylation. PD98059, a MEK inhibitor, suppressed effects of TR on both Cbfa1 transactivation and ERK activation. The results strongly suggest that TR first activates intracellular MEK-ERK-Cbfa1 signaling system thereby promoting mineralization and finally leading to its bone anabolic action.     

Role of perivascular sympathetic nerves and regional differences in the features of sympathetic innervation of the vascular system

Maintenance of blood pressure is mostly dependent on sympathetic "tone", and the sympathetic nerve innervates the entire vascular bed, excepting the capillaries. Although norepinephrine (NE) is the principal neurotransmitter released upon sympathetic nerve stimulation, neuropeptide Y and ATP are cotransmitters in various vascular tissues. In addition, dopamine and epinephrine, as well as acetylcholine, have been shown to be sympathetic neurotransmitters in specific vasculatures. Transmitter NE release is modified by a number of endogenous substances including the transmitter itself. Chronic denervation of the preganglionic fiber induces an increase in NE release per pulse, indicating postganglionic neuronal supersensitivity. So far, three main adrenoceptor types have been shown, alpha1, alpha2 and beta, each of which is further divided into at least three subtypes, as well as the alpha1L-adrenoceptor, a phenotype of the cloned alpha1a-adrenoceptor, in the blood vessel. Thus, the response of vessels with different receptor types to a transmitter varies quantitatively and even qualitatively from one vessel to another. The remarkable diversity in the sympathetic innervation mechanism in the vascular system may play an important role in regional variations in the regulation of blood flow. The sympathetic nerve also exerts long-term trophic action on the blood vessel. In conclusion, the sympathetic nervous system plays an important role not only in the regulation of cardiovascular dynamics but in the maintenance of the vessel structure, as well.