Effects of phototherapy in patients with delayed sleep phase syndrome

Phototherapy was given to six patients with delayed sleep phase syndrome (DSPS). Polysomnography (PSG) and core body temperature were examined before and after phototherapy. Phototherapy was administered to each patient for 5 days, and this treatment not only advanced the delayed sleep phase but also delayed the time of minimum body temperature in all patients. On the PSG, decreases in total sleep time and amounts of stages 2 and REM were observed after phototherapy. These results suggest that phototherapy is effective even in the short term in advancing delays in sleep phase and time of minimum body temperature in DSPS patients.     

Effects of low-dose ketamine on neuropathic pain: An electroencephalogram-electrooculogram/behavioral study

The aim of the present study was to clarify the neurophysiological changes associated with analgesic and behavioral effects of low-dose ketamine HCl in patients suffering from chronic neuropathic pain. Ten in-patients with neuropathic pain participated in this single-blind, placebo-controlled study after giving written informed consent. Following intravenous injections of a saline solution (placebo), three bolus injections of 5 mg ketamine HCl were administered at 5 min intervals. Changes in pain perception were assessed using a numerical rating scale for pain. Behavioral changes, including psychotomimetic effects, were assessed using the Brief Psychiatric Rating Scale (BPRS). Electroencephalograms (EEG) and electrooculograms (EOG) were recorded continuously throughout the testing period. One minute EEG and closed-eye eye movements were quantified. The effects of ketamine were evaluated by comparing the neurophysiological and behavioral parameters obtained from the placebo and ketamine trials. Pain reduction was significantly correlated with ketamine-induced changes in hallucinatory behavior and excitement as measured by the BPRS. Ketamine injections caused a significant decrease in the EEGalpha amplitude without an accompanying reduction in EEG frequency. The EEGalpha amplitude reduction at the right central electrode was significantly related to subjective pain relief. Subanesthetic doses of ketamine significantly decreased rapid eye movements, but did not initiate slow eye movements. In conclusion, the present EEG-EOG/behavioral results indicate that ketamine-induced failure of neural integration between cortical-subcortical regions induces psychotic symptoms and alters pain perception on neuropathic pain.     

A patient with lambda type light-chain disease associated with Crow-Fukase syndrome and autoimmune thrombocytopenia]

A 67-year-old woman, who presented polyneuropathy, pleural effusion, ascites and sclerosing changes in the ribs, was admitted to our hospital on June 17, 1987. On admission, cerebrospinal examination showed a marked protein-cell dissociation and a delay in nerve conduction velocity. Bence-Jones protein was detected in urine, and the immunohistochemical study of biopsied bone marrow of the rib revealed lambda-chain positive plasmacytoma. Serum immunoelectrophoresis, however, showed no monoclonal gamma-globulinemia. From the findings described above, she was diagnosed as having Crow-Fukase syndrome associated with lambda-type light chain disease. Even with a therapy by prednisolone, platelet counts progressively declined to 10,000/ml3. Bone marrow aspiration showed normal number of megakaryocytes. Since platelet-associated IgG was increased to 452 ng/1.0 x 10(8) plt, a diagnosis of autoimmune thrombocytopenia was considered. Melphalan and cyclophosphamide to plasmacytoma resulted in a marked improvement of platelets. In addition, the level of platelet-associated IgG returned to normal range. Polyneuropathy, however, didn't respond to those therapies. It was suggested that both Crow-Fukase syndrome and thrombocytopenia were closely concerned with plasmacytoma but developed in a different manner.     

Regeneration of granule neurons after lesioning of hippocampal dentate gyrus: evaluation using adult mice treated with trimethyltin chloride as a model

The hippocampal dentate gyrus in adult animals is known to contain neural progenitors that proliferate and differentiate into neurons in response to brain injury. Little has been observed, however, on regeneration of the granule cell layer of the dentate gyrus that has been directly injured. Using trimethyltin (TMT)-treated mice as an in vivo model, we evaluated the ability of this layer to regenerate after injury. The administration of TMT induced neuronal death in the dentate gyrus selectively 2 days later, with recovery of granule neurons on day 14 and thereafter. At an early stage (days 2-5) after the damage by TMT treatment, 5-bromo-2'-deoxyuridine (BrdU) incorporation into at least two different types of cells was facilitated in the dentate gyrus: BrdU-positive/neuronal nuclear antigen (NeuN)-negative cells were found predominantly in the subgranular zone and granule cell layer, whereas BrdU-positive/NeuN-positive cells were numerous in the dentate molecular layer and hilus. In addition, expression of proliferating cell nuclear antigen, nestin, NeuroD3, and doublecortin, which are markers for proliferating cells and neural progenitors/neuronal precursors, was extremely enhanced in the dentate gyrus at the early stage after treatment. Double staining revealed that BrdU was colocalized with nestin and doublecortin in the subgranular zone. Behavioral analysis revealed that TMT-induced cognition impairment was ameliorated by day 14 after the treatment. Taken together, our data indicate that the hippocampal dentate gyrus itself is capable of regenerating the neuronal cell layer through rapid enhancement of neurogenesis after injury.     

Evidence for 5-HT4 receptor involvement in the enhancement of acetylcholine release by p-chloroamphetamine in rat frontal cortex

The roles of endogenous serotonin (5-HT) and 5-HT receptor subtypes in regulation of acetylcholine (ACh) release in frontal cortex of conscious rats were examined using a microdialysis technique. Systemic administration (1 and 3 mg/kg, i.p.) of the 5-HT-releasing agent p-chloroamphetamine (PCA) elevated ACh output in a dose-dependent manner. Depletion of endogenous 5-HT by p-chlorophenylalanine significantly attenuated the facilitatory effect of PCA on ACh release. The PCA (3 mg/kg)-induced increase in ACh release was significantly inhibited by local application of the 5-HT₄ receptor antagonists RS23597 (50 μM) and GR113803 (1 μM), while the 5-HT_1A antagonist WAY-100135 (10 mg/kg, i.p.; 100 μM), 5-HT_1A/1B/β-adrenoceptor antagonists (−)-pindolol (8 mg/kg, i.p.) and (−)-propranolol (150 μM), 5-HT_2A/2C antagonist ritanserin (1 mg/kg, i.p.; 10 μM) and 5-HT₃ antagonist ondansetron (1 mg/kg, i.p.; 10 μM) failed to significantly modify the effect of PCA. These results suggest that PCA-induced enhancement of 5-HT transmission facilitates ACh release from rat frontal cortex at least in part through 5-HT₄ receptors.     

Clinicopathological multiplicity of dementia with Lewy bodies

‘Dementia with Lewy bodies (DLB)’ is a generic clinicopathological concept characterized by progressive dementia and Lewy bodies (LB). We examined 23 autopsied DLB cases clinicopathologically and immunohistochemically. These cases were classified into the neocortical type (10 cases), the limbic type (seven cases), the cerebral type (one case) and the brainstem type (none) according to our pathological criteria, which were based on the regional incidence of LB and the degree of neuronal loss in the substantia nigra. Each subtype of DLB was further divided into the common form and the pure form on the basis of the degree of Alzheimer pathology. The remaining five cases were not classified by our pathological criteria, and were designated ‘the senile dementia of Alzheimer type (SDAT) or Alzheimer's disease (AD) type of DLB with neocortical or limbic LB’. We examined how each subtype was correlated with various clinical features, such as the age of disease onset, the clinical duration, the degree of dementia, and the presence or absence of parkinsonism, fluctuating cognition and visual hallucination. The results of this study indicate that DLB can be clinicopathologically divided into a number of subtypes, that each subtype is preferentially correlated with some clinical feature, and that the neocortical type, common form, is the major type of DLB.     

Intracellular signaling in the induction of apoptosis in a human breast cancer cell line by water extract of Mekabu

Background We previously reported that water extract of Mekabu, a kind of seaweed, induced apoptosis in a human breast cancer cell line. In the present study we investigated intracellular signaling in apoptosis, with a focus on caspases.Methods Mekabu extract, obtained with ultrapure water, was used to induce apoptosis in a human breast cancer cell line, MDA-MB231, and DNA fractionation was investigated by flow cytometry and electrophoresis. In addition, using the caspase detection kit Caspa Tag, activation of caspases 3, 6, 8, and 9 was observed under a fluorescence microscope. Furthermore, using antibodies to caspases 3, 8, 9, and Bid, we conducted a protein analysis by Western blotting to determine the activation of these substances.Results Obvious ladder formation demonstrating DNA fractionation was seen, confirming that Mekabu extract induced apoptosis. In the fluorescence microscope observations, activation of caspases 3, 6, and 8, but not caspase 9, was seen. Activated caspases 3 and 8 were detected in the Western blotting analysis, but no proteins of activated caspase 9 or Bid were detected.Conclusion Mekabu extract activates caspases 3, 6, and 8 and contributes to intracellular signaling to induce apoptosis in a human breast cancer cell line. This signaling is not via the mitochondria.     

Acute effects of stereotactic radiosurgery on the kineties of glucose metabolism in metastatic brain tumors: FDG PET study

Hyperacute changes in the expression of glycolysis-associate gene products as well as FDG uptake in tumor cells after high-dose irradiation reflect response of the cells to noxious intervention and may be a potential indicator of the outcome of treatment. To understand acute effects on the kinetics of glucose metabolism of tumors in vivo after high-dose irradiation, we analyzed dynamic FDG PET data in patients with metastatic brain tumors receiving stereotactic radiosurgery. MATERIALS AND METHODS: We studied 5 patients with metastatic brain tumors by means of dynamic FDG PET before and 4 hours after stereotactic radiosurgery. Rate constants of glucose metabolism (K1*- k3*) were determined in a total of 13 tumors by a non-linear least squares fitting method for dynamic PET and arterial blood sampling data. Rate constants after radiosurgery were compared with those before radiosurgery. Changes in the rate constants induced by the therapy were also correlated with changes in tumor size evaluated by CT and/or MRI 6 months later. RESULTS: Four hours after radiosurgery, the phosphorylation rate indicated by k3* was significantly higher (0.080 +/- 0.058) than that before radiosurgery (0.049 +/- 0.023) (p < 0.05, paired t test), but there was no significant change in the membrane transport rates indicated by K1* and k2*. Although increases in the net influx rate constant K* (= K1*k3*/(k2* + k3*)) were correlated with increases in k3*, K* after radiosurgery (0.027 +/- 0.011) was not significantly different from that before the therapy (0.024 +/- 0.012). The reduction in the tumor size was correlated with k3* after radiosurgery. CONCLUSION: Acceleration of the phosphorylation process was demonstrated in vivo in metastatic brain tumors as early as 4 hours after stereotactic radiosurgery, as shown experimentally in vitro in a previous report. The phenomenon may be a sensitive indicator of cell damage.     

Liver stiffness measured by magnetic resonance elastography as a risk factor for hepatocellular carcinoma: a preliminary case�Ccontrol study

Objective

To examine if liver stiffness measured by magnetic resonance elastography (MRE) is a risk factor for hepatocellular carcinoma (HCC) in patients with chronic liver disease.

Methods

By reviewing the records of magnetic resonance (MR) examinations performed at our institution, we selected 301 patients with chronic liver disease who did not have a previous medical history of HCC. All patients underwent MRE and gadoxetic acid-enhanced MR imaging. HCC was identified on MR images in 66 of the 301 patients, who were matched to controls from the remaining patients without HCC according to age. MRE images were obtained by visualising elastic waves generated in the liver by pneumatic vibration transferred via a cylindrical passive driver. Risk factors of HCC development were determined by the odds ratio with logistic regression analysis; gender and liver stiffness by MRE and serum levels of aspartate transferase, alanine transferase, alpha-fetoprotein, and protein induced by vitamin K absence-II.

Results

Multivariate analysis revealed that only liver stiffness by MRE was a significant risk factor for HCC with an odds ratio (95?% confidence interval) of 1.38 (1.05?C1.84).

Conclusion

Liver stiffness measured by MRE is an independent risk factor for HCC in patients with chronic liver disease.

Key Points

? Magnetic resonance elastography can estimate liver stiffness, a marker of hepatic fibrosis. ? Liver stiffness is an independent risk factor of hepatocellular carcinoma (HCC). ? Liver stiffness seems a better indicator of HCC than tumour markers.     

A light and electron microscopic study of the mouse visceral yolk sac endodermal cells in the middle and late embryonic periods, showing the possibility of definitive erythropoiesis

Hematological studies have revealed the importance of the visceral yolk sac (VYS) in the primitive erythropoiesis of mouse embryos at an early stage before day 12. We examined the possibility of the occurrence of extra-embryonic erythropoiesis at a stage later than embryonic day 12 by light and electron microscopic analyses. Surprisingly, a novel structure in the form of erythrocyte-like globules was observed in the VYS endodermal cells. They were consistently present in the VYS endodermal cells from embryonic day 12 until day 18 (birth is day 19), by immunocytochemical and enzyme histochemical analyses. They were immuno-positive for mouse erythrocyte antibody and also positive for the benzidine reaction showing the presence of hemoglobin. The erythrocyte-like globules were shown to be the erythrocytes present in the cytoplasm. These results indicated that erythropoiesis in the VYS endodermal cells continues from the early embryonic stage, as primitive erythropoiesis, until the late stage.