Influence of Paternal 252Cf Neutron Exposure on Abnormal Sperm, Embryonal Lethality, and Liver Tumorigenesis in the F1 Offspring of Mice

Experiments were conducted to determine whether neutron-induced genetic damage in parental germline cells can lead to the development of cancer in the offspring. Seven-week-old C3H male mice were irradiated with ²⁵²Cf neutrons at a dose of 0, 50, 100, or 200 cGy. Two weeks or 3 months after irradiation, the male mice were mated with virgin 9-week-old C57BL females. Two weeks after irradiation, the irradiated male mice showed an increased incidence of sperm abnormalities, which led to embryo lethalities in a dose-dependent manner when they were mated with unirradiated female mice. Furthermore, liver tumors in male offspring of male mice in the 50 cGy group were significantly increased in 19 of 44 (43.2%) animals, in clear contrast to the unirradiated group (1 of 31; 3.2%) ( P < 0.01). In the 100 cGy group, 6 of 39 (15%) mice had lesions. At 3 months after irradiation abnormal sperm and embryonal lethality were not significantly increased. The incidences of liver tumors in male offspring from the 50 cGy, 100 cGy and 200 cGy groups were 6 of 20 (30%), 5 of 22 (23%) and 1 of 19 (5%), respectively, which are not significantly increased compared with the control. It is concluded that increased hepatic tumor risk in the F₁ generation may be caused by genetic transmission of hepatoma-associated trait(s) induced by ²⁵²Cf neutron irradiation.     

Serial magnetic resonance angiography in a case with isolated angiitis of the CNS

Isolated angiitis of the central nervous system (IAC) is an idiopathic type of vasculitis, exclusively affecting small to medium-sized blood vessels of the central nervous system. We report serial angiographical findings, mainly demonstrated with magnetic resonance angiography (MRA) in a case of IAC. A 58-year-old-female came to our hospital because of a sudden headache. Computed tomography (CT) did not show any particular findings. MRA 3 days after the onset revealed diffuse arterial dilatations and segmental stenoses of the middle and anterior cerebral arteries. However, these findings did not lead us to make a diagnosis of IAC. Two days later she was admitted with increased headache and subcortical hemorrhage in the left frontal lobe on CT. Subsequent MRA demonstrated remarkable changes such as dilatated main trunks with segmental stenoses. Steroid pulse therapy was started after definite diagnosis of IAC. She improved gradually and was headache-free 15 days after the onset. Nevertheless, follow-up MRA at 15 days revealed diffusely narrowed anterior and middle cerebral arteries with multiple segmental stenoses. Characteristic findings of angiitis showed improvement at 29 days and had disappeared at 73 days. The patient discontinued corticosteroids and has remained free from headache for the last 7 months.     

Fluctuation of computed tomographic findings in white matter in Alexander's disease

A Japanese boy developed febrile seizures and gait disturbance at 2 years of age and dysarthria a year later. He had generalized tonic-clonic seizures once or twice a year from the age of 4 years. Brain computed tomography (CT) showed symmetric low-density areas in the white matter of the frontal lobes. However, abnormal CT findings fluctuated occasionally, with no apparent change in clinical manifestations. Clinical evaluation at 9 years of age revealed hyper-reflexia, psychomotor retardation, megalencephaly, and slurred nasal speech. Magnetic resonance imaging showed white matter abnormalities, predominantly in the frontal lobes. He was a heterozygote of the Arg239Cys mutation of the glial fibrillary acidic protein gene and was diagnosed with Alexander's disease. Fluctuation of CT findings in white matter may reflect blood-brain barrier dysfunction in Alexander's disease.     

Decreased cerebrospinal fluid levels of beta-phenylethylamine in patients with Rett syndrome

To clarify the mechanism of brain impairment in Rett syndrome, we measured the cerebrospinal fluid levels of beta-phenylethylamine (PEA) in 17 patients with Rett syndrome. Findings were compared with those obtained in age-matched controls and diseased controls. The cerebrospinal fluid level of PEA was significantly lower in patients with Rett syndrome than in the controls (31% of control values). The alteration in the cerebrospinal fluid level of PEA may reflect dopamine system impairment in Rett syndrome.     

Detection of stable chromosome aberrations by FISH in A-bomb survivors: comparison with previous solid Giemsa staining data on the same 230 individuals

PURPOSE: To evaluate the relative abilities of the solid Giemsa staining (conventional) and fluorescence in situ hybridization (FISH) methods in the detection of stable chromosome aberrations in the peripheral blood lymphocytes of A-bomb survivors. MATERIALS AND METHODS: Lymphocytes from a total of 230 A-bomb survivors for whom prior chromosome aberration data had been obtained by the conventional method were recently examined afresh using FISH in which chromosomes 1, 2 and 4 were painted with composite probes. RESULTS: It was found that the early use of the solid Giemsa staining method had allowed the detection of translocations with a mean frequency of 73% of the value for the genome-equivalent translocation frequency (F(G)) that was now obtained using FISH. The disparity may at least in part be due to the reciprocal exchange of seemingly identical amount of chromosome material; such exchanges can escape detection by the conventional method but can be readily identified using FISH. CONCLUSION: It has previously been established that the conventional method can detect about 20% of radiation-induced translocations as abnormal monocentric chromosomes. Present results indicate that an additional 50% can be detected if proper karyotyping is conducted and the remaining 30% are not likely to be detected unless FISH or banding methods are used. Thus, solid Giemsa staining accompanied by karyotyping may not be quite as unsuitable as is generally assumed for retrospective biodosimetry analyses, which deal mainly with stable aberrations.     

Apparent diffusion coefficient of human brain tumors at MR imaging

PURPOSE: To determine if apparent diffusion coefficient (ADC) can be used to differentiate brain tumors at magnetic resonance (MR) imaging. MATERIALS AND METHODS: Institutional review board approval or informed patient consent was not required. MR images were reviewed retrospectively in 275 patients with brain tumors: 147 males and 128 females 1-81 years old, treated between September 1997 and July 2003. Regions of interest were placed manually in tumor regions on MR images, and ADC was calculated with a five-point regression method at b values of 0, 250, 500, 750, and 1000 sec/mm2. ADC values were average values in tumor. All brain tumor subgroups were analyzed. Logistic discriminant analysis was performed by using ADC, age, and patient sex as independent variables to discriminate among tumor groups. RESULTS: A significant negative correlation existed between ADC and astrocytic tumors of World Health Organization grades 2-4 (grade 2 vs grades 3 and 4, accuracy of 91.3% [P < .01]; grade 3 vs 4, accuracy of 82.4% [P < .01]). ADC of dysembryoplastic neuroepithelial tumors (DNTs) was higher than that of astrocytic grade 2 tumors (accuracy, 100%) and other glioneuronal tumors. ADC of malignant lymphomas was lower than that of glioblastomas and metastatic tumors (accuracy, 83.6%; P < .01). ADC of primitive neuroectodermal tumors (PNETs) was lower than that of ependymomas (accuracy, 100%). ADC of meningiomas was lower than that of schwannomas (accuracy, 92.4%; P < .01). ADC of craniopharyngiomas was higher than that of pituitary adenomas (accuracy, 85.2%; P < .05). ADC of epidermoid tumors was lower than that of chordomas (accuracy, 100%). In meningiomas, ADC was not indicative of malignancy grade or histologic subtype. CONCLUSION: ADC is useful for differentiation of some human brain tumors, particularly DNT, malignant lymphomas versus glioblastomas and metastatic tumors, and ependymomas versus PNETs.     

The herbal medicine Rikkunshi-to stimulates and coordinates the gastric myoelectric activity in post-operative dyspeptic children after gastrointestinal surgery

Rikkunshi-to (TJ-43), a gastroprotective herbal medicine, has been used for the symptomatic relief of adult patients with dyspepsia. However, its mechanism has yet to be fully elucidated. The aim of this study is to evaluate the effect of TJ-43 on the gastric myoelectric activity in post-operative dyspeptic patients, whose symptoms persisted for over 1 year after gastrointestinal surgery. Electrogastrography (EGG) recordings were performed to calculate the biomechanical parameters on the dominant peak frequency (DPF). Eight pediatric patients with dyspeptic symptoms after gastrointestinal surgery were examined and six age-matched children without any dyspeptic symptoms were used as controls, and they were compared with nine age-matched children without any dyspeptic symptoms after gastrointestinal surgery as subcontrols. All patients exhibited symptomatic relief after the administration of TJ-43, and the mean symptom score decreased significantly after the treatment of TJ-43 over a 1-month period (P<0.0001). The variability index (VI) and the percentage of normal waves (PNW) were calculated as irregularity parameters of DPF. The power ratio (PR) was calculated as a parameter of the gastric contractile activity. There were no significant differences in the VI and PNW between the controls and patients during the postprandial state after therapy, even though significant differences existed regarding those parameters between the controls and patients before the therapy. There were no significant differences in the DPF, VI, and PNW between the controls and subcontrols. Furthermore, PR exhibited a significant increase after therapy (P<0.05). However, there was a significant difference in the PR between the controls and subcontrols (P<0.05). Postprandial dip was observed in all control subjects, eight patients in the subcontrols, and two patients after administration of TJ-43, respectively. An abnormal gastric electrical activity therefore seems to be an important factor in the pathophysiology of post-operative dyspeptic children. The coordinating and stimulating effect of TJ-43 on the gastric myoelectric activity therefore seems to play an important role in the reduction of dyspeptic symptoms.     

Congenital fibromuscular dysplasia involving multivessels in an infant with fatal outcome

We report the unusual case of a 2-month-old boy with systemic fibromuscular dysplasia (FMD). He presented with congenital renovascular hypertension due to stenosis of the right renal artery, and later developed renal infarction on the contralateral side resulting in renal failure. The boy subsequently died of intracranial haemorrhage at the age of 14 months. During the course, hemiconvulsion caused by a Moyamoya disease-like vascular lesion was noted. Stenotic lesions of both the abdominal aorta and its branches were also revealed by angiography. Post-mortem examination confirmed that the coronary, splenic and mesenteric arteries were also affected and their histological findings were compatible with FMD. To our knowledge, this is the first congenital case of FMD demonstrating a rapidly progressive course resulting in a fatal outcome. In this case, multivessels in both intracranial and extracranial arteries were involved. Conclusion:our case suggests that the nature of fibromuscular dysplasia is congenital in origin and its aetiology, at least in some cases, is a systemic abnormality of vascular development.Abbreviations FMD fibromuscular dysplasia - MMD Moyamoya disease - RVH renovascular hypertension - US ultrasound