Effect of local anesthesia on trigeminal somatosensory-evoked magnetic fields.

For objective neurophysiological evaluation of the function of the trigeminal system, magnetoencephalography- based TSEF (trigeminal somatosensory-evoked field) assessment would be valuable in providing spatial and temporal profiles of cortical responses. However, this necessitates knowledge of how TSEF varies with trigeminal nerve dysfunctions. We introduced a conduction block of the trigeminal nerve using local anesthesia (lidocaine) to temporally mimic nerve dysfunctions, and monitored TSEF changes. Following an electrical stimulation of the lower lip, a magnetic response with peak latency of approximately 20 ms was identified in all participants. Dipole for the peak was estimated on the post-central gyrus in the participant's own magnetic resonance image. After normalization to Montreal Neurological Institute (MNI) space and inter-participant data integration, the summary equivalent current dipole localization among participants remained in the post-central gyrus, suggesting validity of the use of MNI space. Partial anesthesia of the lower lip led to a loss of the waveform characteristics of TSEF for electrical stimulation to the trigeminal nerve. We verified that the 20-ms latency cortical response of TSEF components localized at the primary sensory cortex can serve as a robust neurofunctional marker of experimental trigeminal nerve dysfunction.

Varying the ratio of dietary n-6/n-3 polyunsaturated fatty acid alters the tendency to thrombosis and progress of atherosclerosis in apoE-/- LDLR-/- double knockout mouse.

We have investigated the influence of dietary n-6/n-3 (ù-6/ù-3) polyunsaturated fatty acid-balance on the tendency to arterial thrombosis and the progress of atherosclerosis in apoE-/- LDLR-/- double knockout mouse. Homozygous apoE-/- LDLR-/- double knockout mouse (DKO mice, 129XC57BL/6J background) and male C57BL/6 mice aged 6 weeks were divided into four groups. Each group was fed a diet containing a different n-6/n-3 ratio (Group l: 0.29; Group 2: 1.43; Group 3: 5.00; Group 4: 8), prepared with high linolenic (LNA) flaxseed oil (n-3 rich) and high linoleic (LA) safflower oil (n-6 rich). There were no statistical differences in the gain in body weight between the four groups. After 16 weeks, plasma triglyceride and LDL levels in Group 1 were significantly lower than in the other groups. Conversely, HDL was the highest. After 8 and 16 weeks, the tendency to arterial thrombosis was assessed using a He-Ne laser-induced thrombosis model. The degree of atherosclerosis was measured using the entire aorta method employing image analysis software. The n-6/n-3 ratio had a dose-dependent antithrombotic effect (thrombus volume decreased 23%, Group 1 vs. Group 4), In addition, the extent of atherosclerosis was less in the animals fed a low n-6/n-3 ratio compared with the high n-6/n-3 ratio group (atherosclerotic area decreased 40%, Group 1 vs. Group 4). The lowest n-6/n-3 ratio tested (0.29) was the most effective in suppressing the thrombotic and atherosclerotic parameters in these DKO mice.

Complete nucleotide sequences of attenuated and severe isolates of Leek yellow stripe virus from garlic in northern Japan: identification of three distinct virus types in garlic and leek world-wide.

We have determined the complete nucleotide sequence of three isolates (two severe and one attenuated) of the potyvirus Leek yellow stripe virus (LYSV), the main causal agent of the garlic mosaic disease that is prevalent in Aomori prefecture, northern Japan. They contained 10,296-10,297 nucleotides and encoded a deduced polyprotein of 3,215 amino acids. Sequence variation among the three isolates was 1.5% at both the nucleotide and amino acid levels. Surprisingly, the sequences of all three isolates were quite different from that of recently described garlic isolate of LYSV from China. Sequence similarities among the 5'-UTR and P1 regions were only 56-57% and 52-53%, respectively, raising the possibility that these isolates may actually be distinct virus species. Phylogenetic analyses using 5'-UTR, P1 protein and coat protein revealed that all LYSV isolates described to date can be divided into three groups; i.e., those from leek, those from garlic in northern Japan, and those from garlic in southern Japan, China, and other parts of the world. The garlic isolates from northern Japan were more closely related to LYSV isolates from leek than to garlic isolates from southern Japan and China, suggesting a different origin for the garlic cultivars now cultivated in northern Japan.

A novel spermatogenesis-related factor-1 gene expressed in maturing rat testis.

A rat gene with testis-specific expression coinciding with spermatogenesis was cloned by differential display. This spermatogenesis-related factor-1 (SRF-1) gene was not expressed in other organs. Testicular expression was detected from 5 weeks of age and increased up to 15 weeks; this level of expression was maintained for 63 weeks. The 750-bp cloned gene was coded for an open reading frame of 202 amino acids. According to in situ hybridization at 7 weeks, this gene was expressed mainly in spermatocyte. The gene product may function as a molecular motor in meiosis, as the deduced amino acid sequence showed partial homology with kinesin-related proteins. The action of this gene and its product with respect to division of reproductive cells requires further investigation.

Increased systemic oxygen consumption offsets improved oxygen delivery during dobutamine infusion in newborn lambs.

OBJECTIVE: To determine: 1) if dobutamine elicited a thermogenic response during postnatal development; and 2) if this response impacted on the balance between systemic O(2) delivery (DO(2)) and O(2) consumption (VO(2)), and involved one or a combination of adrenoceptor subtypes. DESIGN: Prospective non-randomized unblinded study. SETTING: University research laboratory. SUBJECTS: Thirty-five Border-Leicester cross lambs used in a main study performed at 1-2 days (n=7), 7-10 days (n=7), and 6-8 weeks (n=8), and in a adrenoceptor blockade substudy performed at 1-2 days (n=13). INTERVENTIONS: Lambs were instrumented under anaesthesia and dobutamine was infused at incremental rates of 1-40 microg/kg per minute. In separate subgroups of 1-2 day-old lambs, dobutamine was infused after selective or combined alpha1, beta 1, and beta 2-adrenoceptor blockade. MEASUREMENTS: Cardiac output, aortic and pulmonary arterial blood gases, and body temperature were measured. DO(2) and VO(2) were calculated. MAIN RESULTS: Dobutamine increased DO(2) similarly at all three ages. Dobutamine also increased VO(2) in the absence of muscle shivering, but the average rise in 1-2 day-old lambs was sevenfold to 12-fold greater (P<0.001) than in 7-10 day-old and 6-8 week-old animals, was associated with an increase in systemic O(2) extraction, and accounted for approximately 90% of the rise in DO(2). Body temperature rose by 1.3+/-0.5 degrees C in 1-2 day-old animals (P<0.001), but was unchanged in 7-10 day-old or 6-8 week-old lambs. In 1-2 day-old lambs, rises in DO(2), VO(2), and body temperature induced by dobutamine were not affected by selective alpha1, beta1 or beta2 adrenoceptor blockade, but were markedly attenuated by combined adrenoceptor blockade. CONCLUSIONS: A substantial rise in VO(2) which accompanied a pronounced thermogenic effect of dobutamine in newborn lambs utilized most of the associated increase in DO(2) and appeared to be dependent on activation of multiple adrenoceptor subtypes.

Node-positive mucosal gastric cancer: a follow-up study.

BACKGROUND: Lymph node metastasis from mucosal gastric carcinoma is rare and the prognosis of the patients has seldom been reported. METHODS: Forty-five patients with node-positive mucosal gastric cancer were studied. They accounted for 2.5% of 1770 patients with mucosal gastric cancer who underwent gastrectomy with lymphadenectomy at the National Cancer Center Hospital, Tokyo. The clinicopathological features were studied and the current clinical status was sought. RESULTS: The majority of patients (87%) were treated with D2 lymphadenectomy. The metastasis was confined to the perigastric nodes (pN1 by Japanese classification) in 30 patients (67%). The number of positive nodes was less than seven (pN1 by TNM) in 42 patients (93%). Two patients had para-aortic nodal metastasis. The median follow-up period was 11 years. Four patients died of definite or possible recurrent disease and the disease-specific 5- and 10-year survival rates were 95 and 89%, respectively. CONCLUSIONS: Although nodal metastasis is an important prognostic factor for gastric cancer, the prognosis was excellent as long as the primary tumor was confined to the mucosa and was treated with gastrectomy and lymphadenectomy.

[Current status and problem of adjuvant chemotherapy for curatively resected gastric cancer].

Randomized controlled trials (RCT) on adjuvant chemotherapy for gastric cancer published in the West and Japan were reviewed. Although several small trials showed positive data, adjuvant chemotherapy for curatively resected gastric cancer has been thought to be ineffective in western countries. Results of Japanese RCTs also have not become evidence of its benefit. Despite this, suggestive data by non-predefined subset analyses of old RCTs have been misread as definitive evidence of benefit because of less understanding of clinical statistics in Japan. As a result most Japanese patients have received postoperative adjuvant chemoimmunotherapy. Recently understanding of clinical trial has spread gradually and well designed RCTs with sufficient sample size have been reported. First of all we have to determine the efficacy of adjuvant chemotherapy by carefully designed RCT using surgery alone arm as control.

Endoscopic characteristics of low-grade gastric mucosa-associated lymphoid tissue lymphoma after eradication of Helicobacter pylori.

BACKGROUND AND AIMS: It was recently reported that low-grade gastric lymphoma of mucosa-associated lymphoid tissue (MALT) was regressed by the eradication of Helicobacter pylori. The aim of this study was to confirm the effect of H. pylori eradication on low-grade gastric MALT lymphoma and to investigate the whitish mucosa that appeared with regression of the lesions. METHODS: Forty-seven H. pylori-positive patients with low-grade gastric MALT lymphoma were treated by using triple therapy. Biopsy specimens were histologically graded and B cell clonality was examined by using reverse transcription-polymerase chain reaction before and after eradication treatment. The relationship between the appearance of whitish mucosa and the degree of gastric gland loss was evaluated. RESULTS: Histologic regression was observed 2 months after eradication therapy in 42 of 47 patients. However, B cell monoclonality changed to polyclonality in only 23 patients during the follow-up period. The appearance of whitish mucosa in patients who showed histologic regression became more frequent as the degree of gastric gland loss increased (P< 0.001). CONCLUSIONS: Most low-grade gastric MALT lymphoma histologically regressed after H. pylori eradication. The appearance of whitish mucosa after histologic regression reflected the degree of gastric gland loss. Whitish mucosa is an endoscopic characteristic and may be an endoscopic marker for regression of low-grade gastric MALT lymphoma.

Scanning electron microscopy subsequent to a combined treatment of NaOCl and EDTA in some non-collagenous calcified matrixes.

Using backscattered electron (BSE) imaging and scanning electron microscopy, subsequent to a combined treatment of sodium hypochlorite (NaOCl) and ethylenediamine tetra-acetic acid (EDTA) or only with EDTA etching, we observed some structures of non-collagenous calcified matrixes with the aim of revealing the correlation of deposition between calcification degree and organic amount. In human tooth enamel, the NaOCl-EDTA method eroded more intensively the hypocalcified prisms of enamel tufts containing a relatively large amount of EDTA-insoluble organic matter than the hypercalcified normal prismatic enamel containing a small amount of the organic matter. Afibrillar cementum, one of the non-collagenous calcified tissues similar to the enamel, has been reported to consist of organic-rich and poor incremental lamellae. The BSE imaging showed an alternation pattern of hypocalcification and hypercalcification. The hypocalcified lamellae were retained by EDTA etching, while the hypercalcified lamellae showed a resistance against the NaOCl-EDTA method. In the non-collagenous calcareous concretions of human pineal body, organic-rich and poor, and hyper- and hypocalcified incremental lamellae have been reported. The deposition pattern of calcification degree and organic amount was similar to that in afibrillar cementum, and the hypercalcified lamellae showed a resistance against the NaOCl-EDTA method. In conclusion, the high and the lower calcified regions of non-collagenous calcified matrixes contained smaller and larger amounts of EDTA-insoluble organic matter respectively. Moreover, scanning electron microscopy subsequent to the NaOCl-EDTA method corresponding to the BSE imaging clearly showed fine calcified structures compared with the BSE imaging.

Treatment of primary gastric lymphoma: experience in the National Cancer Center Hospital, Tokyo.

The single institutional experience of the treatment of primary gastric lymphoma is presented in chronological order. Between 1963 and 1986, 74 patients were treated with various uncontrolled methods and resection line involvement was seen in seven cases. Between 1987 and 1995, a prospective study was conducted employing total gastrectomy with systematic lymphadenectomy, followed by chemotherapy for cases with lymph node metastasis. Fifty patients were enrolled and the 5-year survival rate was 86%. Thorough histological examinations of the resected specimens revealed multiple foci in the stomach and nodal involvement in 36% and 50% of cases, respectively. Since 1995, the effects of eradication of Helicobactor pylori have been examined in association with the introduction of the histological diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma. Special attention should be paid to the elevated type tumors because they could metastasize to lymph nodes preserving the features of "low-grade" MALT lymphoma.

Aporphine glycosides from Stephania cepharantha seeds.

Two new aporphine glycosides, stesakine-9-O-beta-D-glucopyranoside (1) and N-methylasimilobine-2-O-beta-D-glucopyranoside (2), were isolated from the seeds of Stephania cepharantha cultivated in Japan, together with 16 known alkaloids. The structures of 1 and 2 were spectroscopically determined by comparison of their (1)H and (13)C NMR data with those of stesakine (11) and N-methylasimilobine (12), respectively.

Phosphate as a limiting factor for the cell division of tobacco BY-2 cells.

The re-addition of phosphate to tobacco BY-2 cells deprived of phosphate for 3 d induced cells to semi-synchronously re-enter the cell cycle from a static state. Though the addition of auxin to auxin-starved tobacco BY-2 cells also induced cell division (Ishida et al. 1993), some major differences were observed between these two systems. BY-2 cells lost the ability to re-enter the cell cycle after prolonged periods of auxin deprivation, but in contrast retained this ability after longer periods in the absence of phosphate. By differential cDNA screening we identified a phosphate-induced gene phi-1. phi-1 was rapidly induced by the addition of phosphate with transcript levels starting to decrease by the start of DNA synthesis. phi-1 does not share any significant homology with any gene with known functions over its full length. However, the N-terminus shared some homology with plasma membrane ATPases suggesting that it may be involved in some process of phosphorylation. Immunolocalization of the phi-1 gene product revealed that it rapidly accumulated in the cytoplasm prior to the start of plastid and nuclear DNA synthesis. These results are discussed in relation to the role of phosphate in inducing plant cell division.

Increased heating efficiency of hyperthermia using an ultrasound contrast agent: a phantom study.

It is known that there are large temperature elevations in proximity to air bubbles during US (ultrasound) heating. The existence of tiny air bubbles in the target tissue may enhance the temperature elevation in US hyperthermia. To examine this hypothesis, phantom tissue experiments using an US contrast agent consisting of tiny air bubbles surrounded by a 5% (w/v) human albumin shell (Alb) were performed. As a phantom tissue, a 2 cm cube of beef was used. The phantom tissue was heated with or without the US contrast agent by an US hyperthermia device for 3 min. The heating device was operated at 1.5 MHz with the US intensity of 0.9 W/cm2. Physiological saline solution, iodized oil, and ethanol were used for control experiments. The effect of multiple needle punctures to the beef phantom was also examined. The temperature elevation rate (TER) was defined as the ratio of temperature elevation by heating with Alb or control materials to the temperature elevation by US heating alone. The TER of Alb was 1.7, whereas the TERs of the control materials and of the multiple needle punctures were approximately 1. The administration of Alb significantly increased the temperature in US hyperthermia. In addition, the heating efficiency of Alb was compared to the effect of an increase in the US intensity. Phantom tissue was heated at various US intensities. When the US intensity was increased from 0.9 to 1.8 W/cm2, the temperature elevated by approximately 1.7-fold. Thus, the effect of the administration of Alb was almost equivalent to the effect of increase in US power intensities from 0.9 to 1.8 W/cm2 in the present experimental settings. The results suggest that the US contrast agent can be a potential enhancer in US hyperthermia.

[Differences between Japan and the west in treatment strategy for gastrointestinal cancer--gastric cancer].

Diagnosis, staging, and treatment strategies for gastric cancer were reviewed with regard to differences between Japan and the West. In Japan, detection of early gastric cancer is common due to mass screening and widespread use of endoscopy. Treatment options for gastric cancer vary from endoscopic mucosal resection to the super-extended lymphadenectomy. Correct selection from the available options requires meticulous staging including endoscopy with indigocarmine spray, double contrast barium meal study, endoscopic ultrasonography, CT, abdominal ultrasound, and sometimes barium enema to detect possible peritoneal seeding. Western gastric cancer patients are, on average, 10 years older, more obese, have more cardiopulmonary disease, and more advanced tumors than Japanese patients. Because of the high proportion of patients with extensive disease at presentation in the West, laparoscopic staging is frequently used to avoid non-curative surgery. In Japan, D2 lymphadenectomy is the standard, and now a more extended surgery (D4) is being evaluated in a randomized controlled study, while D2 lymphadenectomy has been reported to be associated with high morbidity and mortality in European studies. Adjuvant chemotherapy is more commonly used in Japan, mostly with oral fluorouracil. However, no regimen has been shown effective in the adjuvant setting in either Japanese and Western studies.

New ferromagnetic bone cement for local hyperthermia.

We have developed a ferromagnetic bone cement as a thermoseed to generate heat by hysteresis loss under an alternate magnetic field. This material resembles bioactive bone cement in composition, with a portion of the bioactive glass ceramic component replaced by magnetite (Fe3O4) powder. The temperature of this thermoseed rises in proportion to the weight ratio of magnetite powder, the volume of the thermoseed, and the intensity of the magnetic field. The heat-generating ability of this thermoseed implanted into rabbit and human cadaver tibiae was investigated by applying a magnetic field with a maximum of 300 Oe and 100 kHz. In this system, it is very easy to increase the temperature of the thermoseed in bone beyond 50 degrees C by adjusting the above-mentioned control factors. When the temperature of the thermoseed in rabbit tibiae was maintained at 50 to 60 degrees C, the temperature at the interface between the bone and muscle (cortical surface) surrounding the material rose to 43 to 45 degrees C; but at a 10-mm distance from the thermoseed in the medullary canal, the temperature did not exceed 40 degrees C. These results demonstrate that ferromagnetic bone cement may be applicable for the hyperthermic treatment of bone tumors.

Transgenic potato expressing a double-stranded RNA-specific ribonuclease is resistant to potato spindle tuber viroid.

We have produced transgenic potato lines expressing the yeast-derived double-stranded RNA-specific ribonuclease pac1. Five lines of pac1 potato (Solanum tuberosum L., cultivar Russet Burbank) challenged with potato spindle tuber viroid (PSTVd) suppressed PSTVd infection and accumulation. All of the progeny potato tubers produced by resistant plants were also free of PSTVd. Because the pac1 gene product digested PSTVd in vitro, double-stranded regions in PSTVd molecule and/or replicative intermediates may be targeted by pac1 gene product in the transgenic potato plant.

A phase I and II clinical trial of a newly developed ultrasound hyperthermia system with an improved planar transducer.

PURPOSE: The clinical usefulness of a newly developed ultrasound hyperthermia system was evaluated. METHODS AND MATERIALS: The hyperthermia system uses a modified planer transducer operated at frequencies of 0.5, 1.0, and 1.5 MHz. The transducer has a nonvibrating part at the center to reduce the central hot spot. Frequency sweeping technique is also used to eliminate the annular hot spot around the center. Thirty-eight tumors in 29 patients were examined in this study. In 35 tumors, hyperthermia was given in conjunction with irradiation and/or chemotherapy, and in the remaining 3 tumors, hyperthermia alone was given. In all, a total of 153 hyperthermia sessions were performed. RESULTS: The number of hyperthermia sessions per tumor ranged from 1 to 7 (mean, 4.0 +/- 1.3). The number of intratumor thermometry points per session ranged from 1 to 8 (mean, 4.3 +/- 1.5). The average intratumor temperature for tumors with a maximum depth of <3 cm, 3-6 cm, and >6 cm was 42.1 +/- 1.2, 41.7 +/- 1.4, and 39.9 +/- 2.0 degrees C, respectively. The percentage of monitored intratumor points with temperature exceeding 42 degrees C was 56 +/- 31%, 43 +/- 34%, and 21 +/- 24%, respectively. Of the 30 evaluable tumors treated with combined irradiation, 12 showed complete response, 14 partial response, and 4 no change. Observed complications included pain at the treatment site in 13 of the 153 treatment sessions and vesicle formation in 3 of the 38 treatment sites. No serious complication was seen. CONCLUSIONS: These results indicate that the newly developed ultrasound hyperthermia system is clinically useful for the treatment of localized superficial and subsurface tumors with a maximum tumor depth of no more than 6 cm.

[Benign infantile mitochondrial myopathy caused by reversible cytochrome c oxidase deficiency].

A 2-month-old girl had generalized weakness, profound muscular hypotonia, hepatomegaly and severe lactic acidosis. She needed ventilatory support. Muscle specimen taken at 2 months showed ragged-red fibers, abnormal mitochondria, and reduced cytochrome c oxidase (CCO) staining Biochemical analysis showed CCO activity to be reduced to about 16% of the normal mean. She received carnitine and coenzyme Q10 supplementation from the age of 3 months and abnormal blood lactate values declined to near normal values during the first three weeks. Gradually her condition started to improved: she held her head at 9 months, and walked alone at 15 months. The second biopsy specimen at 3 years and 8 months showed almost normal CCO staining and she was free of clinical signs. This case is an example of a rare benign infantile mitochondrial myopathy caused by CCO deficiency. Early diagnosis is crucial to provide intensive treatment until spontaneous clinical improvement appears. We concluded that carnitine and coenzyme Q10 supplementation was a useful treatment for clinical improvement in patients with a benign infantile mitochondrial myopathy caused by CCO deficiency.