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Vascular cognitive impairment (VCI) plays an important role in dementia in elderly people, and refers to the contribution of vascular pathology to the entire spectrum of cognitive disorders, ranging from mild cognitive impairment to severe dementia, as well as the pathological spectrum, from 'pure' Alzheimer disease through degrees of vascular comorbidity to 'pure' vascular dementia. In the present study, we investigated the relationship between cognitive dysfunction and systemic metabolic disorders, by employing deep learning (DL). We studied 202 patients (73.4 ± 13.0 years), 94.6% of whom were undergoing treatment for lifestyle diseases, and 68.8% of whom had a history of cerebrovascular disorder. We evaluated cognitive dysfunction by performing a Mini Mental State Examination (MMSE). We performed general blood examination, including Complete Blood Count and Basic Metabolic Panel, and measured cerebral blood oxygenation in the prefrontal cortex (PFC) using time-resolved near infrared spectroscopy (TNIRS). We then used deep neural networks to assess the MMSE scores of the subjects based on the TNIRS parameters and the blood examination data, independently. Next, we compared predicted MMSE scores based on the TNIRS and the blood examination. There was a significant positive correlation between the TNIRS parameters and the blood examination data (r = 0.6, p 0.01). These observations suggest that cognitive dysfunction in patients with VCI may be caused by combinations of systemic metabolic disorders such as energy and oxygen metabolisms and cerebral circulatory disturbance due to arteriosclerosis resulting from lifestyle-related diseases.

The incidence of stress-induced psychological and somatic diseases has been increasing rapidly, and it is important to clarify the neurophysiological mechanisms of stress response in order to establish effective stress management methods. We previously reported that the prefrontal cortex (PFC) plays an important role in stress response. In the present study, we employed near-infrared spectroscopy (NIRS) and electroencephalography (EEG) to investigate the characteristics of PFC activity during mental arithmetic tasks. A two-channel NIRS device was used to measure hemoglobin (Hb) concentration changes in the bilateral PFC during a mental arithmetic task (2 min) in normal adults. Simultaneously, EEG was used to also measure bilateral PFC activity during the same task. We evaluated concentration changes of oxy-Hb induced by the task while analyzing α wave changes using power spectrum analysis. It was observed that oxy-Hb in the bilateral PFC increased significantly during the task (p 0.05), while α wave power in the PFC decreased significantly (p 0.01). The present results indicate that mental stress tasks caused the activation of the bilateral PFC. Simultaneous measurements of NIRS and EEG are useful for evaluating the neurophysiological mechanism of stress responses in the brain.

We present an unobtrusive cuff-less sphygmomanometer based on contact-type and optical pulse sensors for continuous and minimally invasive monitoring of blood pressure (BP). We developed a cuff-less sphygmomanometer that utilizes the pulse arrival time (PAT) to estimate continuous BP. To assess its accuracy, we recruited 10 healthy subjects in whom we carried out BP studies using the cuff-less sphygmomanometer compared with a standard cuff-type device in a stationary sitting patient. Preliminary results showed that the mean difference (MD) of estimated systolic blood pressure and diastolic blood pressure were 0.96 ± 9.6 (mean ± SD) mmHg and 1.14 ± 7.5 mmHg, respectively, compared to the control. The corresponding correlation between the estimated BP values and controls were 0.78 for systolic blood pressure (p 0.01) and 0.69 for diastolic blood pressure (p 0.01); thus, there were significant correlations. These results suggest that the developed cuff-less sphygmomanometer has the potential for continuous BP monitoring. Finally, we conducted a preliminary study of simultaneous monitoring of cuff-less BP and near-infrared spectroscopy to evaluate the potential for assessment of autonomic nervous system functions during mental stress tasks.

We present an unobtrusive cuff-less sphygmomanometer based on contact-type and optical pulse sensors for continuous and minimally invasive monitoring of blood pressure (BP). We developed a cuff-less sphygmomanometer that utilizes the pulse arrival time (PAT) to estimate continuous BP. To assess its accuracy, we recruited 10 healthy subjects in whom we carried out BP studies using the cuff-less sphygmomanometer compared with a standard cuff-type device in a stationary sitting patient. Preliminary results showed that the mean difference (MD) of estimated systolic blood pressure and diastolic blood pressure were 0.96 ± 9.6 (mean ± SD) mmHg and 1.14 ± 7.5 mmHg, respectively, compared to the control. The corresponding correlation between the estimated BP values and controls were 0.78 for systolic blood pressure (p < 0.01) and 0.69 for diastolic blood pressure (p < 0.01); thus, there were significant correlations. These results suggest that the developed cuff-less sphygmomanometer has the potential for continuous BP monitoring. Finally, we conducted a preliminary study of simultaneous monitoring of cuff-less BP and near-infrared spectroscopy to evaluate the potential for assessment of autonomic nervous system functions during mental stress tasks.

Vascular cognitive impairment (VCI) plays an important role in dementia in elderly people, and refers to the contribution of vascular pathology to the entire spectrum of cognitive disorders, ranging from mild cognitive impairment to severe dementia, as well as the pathological spectrum, from ‘pure’ Alzheimer disease through degrees of vascular comorbidity to ‘pure’ vascular dementia. In the present study, we investigated the relationship between cognitive dysfunction and systemic metabolic disorders, by employing deep learning (DL). We studied 202 patients (73.4 ± 13.0 years), 94.6% of whom were undergoing treatment for lifestyle diseases, and 68.8% of whom had a history of cerebrovascular disorder. We evaluated cognitive dysfunction by performing a Mini Mental State Examination (MMSE). We performed general blood examination, including Complete Blood Count and Basic Metabolic Panel, and measured cerebral blood oxygenation in the prefrontal cortex (PFC) using time-resolved near infrared spectroscopy (TNIRS). We then used deep neural networks to assess the MMSE scores of the subjects based on the TNIRS parameters and the blood examination data, independently. Next, we compared predicted MMSE scores based on the TNIRS and the blood examination. There was a significant positive correlation between the TNIRS parameters and the blood examination data (r = 0.6, p < 0.01). These observations suggest that cognitive dysfunction in patients with VCI may be caused by combinations of systemic metabolic disorders such as energy and oxygen metabolisms and cerebral circulatory disturbance due to arteriosclerosis resulting from lifestyle-related diseases.

The incidence of stress-induced psychological and somatic diseases has been increasing rapidly, and it is important to clarify the neurophysiological mechanisms of stress response in order to establish effective stress management methods. We previously reported that the prefrontal cortex (PFC) plays an important role in stress response. In the present study, we employed near-infrared spectroscopy (NIRS) and electroencephalography (EEG) to investigate the characteristics of PFC activity during mental arithmetic tasks. A two-channel NIRS device was used to measure hemoglobin (Hb) concentration changes in the bilateral PFC during a mental arithmetic task (2 min) in normal adults. Simultaneously, EEG was used to also measure bilateral PFC activity during the same task. We evaluated concentration changes of oxy-Hb induced by the task while analyzing α wave changes using power spectrum analysis. It was observed that oxy-Hb in the bilateral PFC increased significantly during the task (p < 0.05), while α wave power in the PFC decreased significantly (p < 0.01). The present results indicate that mental stress tasks caused the activation of the bilateral PFC. Simultaneous measurements of NIRS and EEG are useful for evaluating the neurophysiological mechanism of stress responses in the brain.

Multi-channel NIRS, so-called optical topography (OT), allows functional mapping of the cortex; however, it takes a long time to set optodes on the head and is relatively expensive. Thus, OT is not suitable as a screening test of brain disorders evaluating many subjects. Recently, a wearable two-channel continuous wave NIRS (CW-NIRS) device has been developed. Such a simple NIRS device may be applicable as a screening test of brain disorders; however, its reliability in measurements of brain function is not yet clear. Here, we tested a two-channel CW-NIRS, which employs single LED (800 nm) for measurement of total hemoglobin (t-Hb) changes. We measured t-Hb changes in the bilateral prefrontal cortex (PFC) during mental arithmetic tasks, employing the CW-NIRS and time-resolve NIRS (TNIRS). The left-right asymmetry of the PFC activity was evaluated by calculating the laterality index (LI; (R-L)/(R + L) of t-Hb), which reflects mental stress. The interval between CW-NIRS and TNIRS measurements was 1-13 days. A significant positive correlation was observed between LI measured by CW-NIRS and TNIRS. These results suggest the reliability of the simple CW-NIRS, and it may be applicable to prevent stress-induced various diseases. Finally, it should be emphasized that the left-right asymmetry of PFC activity is relatively stable.

Near infrared spectroscopy (NIRS) has been applied to measurements of cerebral blood oxygenation (CBO) in normal subjects and patients with various brain disorders including cerebrovascular diseases. However, it is not known whether NIRS allow us to measure CBO correctly in patients with abnormal cortices where optical characteristics such as optical pathlength (OP) may differ from those in normal cortex. In the present study, employing a time-resolved NIRS (TNIRS), we compared baseline hemoglobin (Hb) concentrations and OPs between normal and abnormal cortices in chronic stroke patients. We studied five patients with chronic cerebral infarction (two males, three females, age 59.0 ± 24.2 years) who were admitted to the University Hospital of Fukushima Prefectural Medical University. Employing TNIRS (TRS-20, Hamamatsu Photonics), we measured baseline Hb concentrations and OPs (760, 800, 830 nm) at various positions on the head. We observed that deoxy-Hb concentrations were significantly lower on the affected side (p 0.01), and the tissue oxygen saturation was significantly higher than that on the affected side (p 0.01), suggesting that oxygen consumption was reduced on the affected side. In addition, the OPs (760, 800 nm) were significantly longer on the affected side (p 0.05); these changes might be caused by a possible increase of cerebrospinal fluid layer associated with brain tissue degeneration by ischemia. The present results suggest that NIRS should be performed on patients with abnormal cerebral cortices, giving special consideration to the possible difference in optical characteristics between normal and abnormal brain tissues.

Near infrared spectroscopy (NIRS) has been applied to measurements of cerebral blood oxygenation (CBO) in normal subjects and patients with various brain disorders including cerebrovascular diseases. However, it is not known whether NIRS allow us to measure CBO correctly in patients with abnormal cortices where optical characteristics such as optical pathlength (OP) may differ from those in normal cortex. In the present study, employing a time-resolved NIRS (TNIRS), we compared baseline hemoglobin (Hb) concentrations and OPs between normal and abnormal cortices in chronic stroke patients. We studied five patients with chronic cerebral infarction (two males, three females, age 59.0 ± 24.2 years) who were admitted to the University Hospital of Fukushima Prefectural Medical University. Employing TNIRS (TRS-20, Hamamatsu Photonics), we measured baseline Hb concentrations and OPs (760, 800, 830 nm) at various positions on the head. We observed that deoxy-Hb concentrations were significantly lower on the affected side (p < 0.01), and the tissue oxygen saturation was significantly higher than that on the affected side (p < 0.01), suggesting that oxygen consumption was reduced on the affected side. In addition, the OPs (760, 800 nm) were significantly longer on the affected side (p < 0.05); these changes might be caused by a possible increase of cerebrospinal fluid layer associated with brain tissue degeneration by ischemia. The present results suggest that NIRS should be performed on patients with abnormal cerebral cortices, giving special consideration to the possible difference in optical characteristics between normal and abnormal brain tissues.

Multi-channel NIRS, so-called optical topography (OT), allows functional mapping of the cortex; however, it takes a long time to set optodes on the head and is relatively expensive. Thus, OT is not suitable as a screening test of brain disorders evaluating many subjects. Recently, a wearable two-channel continuous wave NIRS (CW-NIRS) device has been developed. Such a simple NIRS device may be applicable as a screening test of brain disorders; however, its reliability in measurements of brain function is not yet clear. Here, we tested a two-channel CW-NIRS, which employs single LED (800 nm) for measurement of total hemoglobin (t-Hb) changes. We measured t-Hb changes in the bilateral prefrontal cortex (PFC) during mental arithmetic tasks, employing the CW-NIRS and time-resolve NIRS (TNIRS). The left-right asymmetry of the PFC activity was evaluated by calculating the laterality index (LI; (R-L)/(R + L) of t-Hb), which reflects mental stress. The interval between CW-NIRS and TNIRS measurements was 1–13 days. A significant positive correlation was observed between LI measured by CW-NIRS and TNIRS. These results suggest the reliability of the simple CW-NIRS, and it may be applicable to prevent stress-induced various diseases. Finally, it should be emphasized that the left-right asymmetry of PFC activity is relatively stable.

Muscle infarction after bypass graft occlusion for atherosclerotic occlusive disease in non-diabetic patients is uncommon. The diagnosis of minor muscle necrosis not requiring surgical debridement in the presence of an acute graft occlusion is often difficult to make. The incidence of this problem in non-diabetic patients with artheroscleotic disease as well as the utility of magnetic resonance imaging in the diagnosis of minor muscle necrosis are presented below.

Two sets of optically active 5-substituted-2-(3-pyridyl)thiazolidin-4-ones, highly potent and selective antagonists of platelet activating factor (PAF), displayed apparently different anti-PAF activities between their enantiomers, wherein these activities depend markedly on the absolute configuration of the 2-position in the thiazolidin-4-ones.

1. 1. Monte Carlo Calculations by a Modified Vector Processor. At Japan Atomic Energy Research Institute, four Monte Carlo codes KENO-IV, MORSE-DD, and VIM and MCNP were vectorized to examine the adaptability of vector processors for these codes. The performances and vectorization rates of the vectorized versions were not good except KENO-IV on SX-2 vector processor, on which the vectorized version attained three times faster speed compared to its scalar version. According to the experience with the vectorization, some additional features specialized for Monte Carlo calculations will improve the vectorization rates of the four codes. Functions of the features and anticipated effects are presented. 2. 2. Speedup of Monte Carlo Criticality Calculation by a Parallel Processor. The authors implemented the Monte Carlo code KENO-IV on a parallel processor system Topology 1000 with three processing units under control of SUN workstation. The Hansen-Roach 16-group cross section set was used for the calculation. A computation for a bare sphere of highly enriched uranium metal showed that the system attained 2.7 times speedup compared to that of one processing unit.

The identification of predictive indicators of radiosensitivity is extremely useful in selecting patients suited for preoperative radiotherapy and avoiding unnecessary preoperative treatment. In this study, we evaluated the possible role of the immunohistochemical expression pattern of p53 and Ku70 protein in determining tumor radiosensitivity in rectal cancer before preoperative irradiation. We examined pretreatment biopsy materials from 111 patients by immunohistochemistry. The expression pattern of p53 and Ku70 was evaluated for association with tumor radiosensitivity, which was defined according to the criteria of the Japanese Research Society for Cancer of the Colon and Rectum. There was a significant correlation between the expression pattern of p53 and tumor radiosensitivity (P = 0.045); Ku70 and tumor radiosensitivity (P0.001); and the combination of p53 and Ku70, and tumor radiosensitivity (P0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in both p53 and Ku70-positive cases for radioresistance were all superior to those of the group positive for p53 alone. In conclusion the examination of the combination of p53 and Ku70 may predict the radiosensitivity of rectal cancer before preoperative irradiation.

The histoculture drug sensitivity assay (HDRA) has been demonstrated to have high predictability for resistance, sensitivity, and survival for gastrointestinal cancer (Clin Cancer Res 1: 305-311, 1995; Clin Cancer Res 1: 1537-1543, 1995). In this report, we evaluated the clinical usefulness of the HDRA in ovarian cancer. HDRA was performed on tumors from patients with ovarian cancer. Eighty-five cases (97%) were evaluable. Tumor fragments were cultured on collagen-sponge gels. The cultures were incubated with cisplatin (CDDP) for seven days. Cell viability were assessed with the MTT end point. The optimal cut off concentration of CDDP was determined to be 25 micrograms/ml by correlation with the historical clinical response rate to CDDP. HDRA results were correlated to clinical response of 15 patients who received CDDP-based therapy that included doxorubicin and cyclophosphamide (CAP therapy). The true positive rate was 88%, the true negative rate was 86%, the sensitivity was 88%, the specificity was 86%, and the accurate prediction rate was 87% when HDRA results were compared to the response of the treated patients. The data suggest that the HDRA is capable of predicting the response to antitumor chemotherapy in patients with ovarian cancer and that measuring response to CDDP can be useful for optimization of CAP chemotherapy for patients with this disease.

We report a case of stage IV ovarian clear cell adenocarcinoma successfully controlled by a combination of cisplatin-cyclophosphamide (CP) and paclitaxel-carboplatin (TJ). A 64-year-old female with advanced ovarian cancer and pleural effusion underwent 4 courses of combination chemotherapy with CP. The giant ovarian tumor showed a relative reduction in size and the pleural effusion disappeared. Serum CA-125 levels and CA 19-9 levels markedly decreased. Thus, the patient underwent a total hysterectomy and bilateral salphingoophorectomy. During the operation, a giant ovarian clear cell adenocarcinoma was found, but there was no peritoneal dissemination and no cancer cells in her peritoneal fluid. Thereafter, she underwent 3 courses of combination chemotherapy with TJ. She has had 13 months of stable, tumor-free survival since the operation and normal serum CA-125 and CA 19-9 levels. Ovarian clear cell adenocarcinoma generally responds poorly to cisplatin and carboplatin, but in combination chemotherapy with paclitaxel-carboplatin these may be effective.

We examined the effects of tetragastrin on mucin (mucus glycoprotein) content and mucosal damage in the rat stomach and duodenum. Following an injection of tetragastrin (12, 120, or 400 microg/kg subcutaneously), no macroscopic damage was found to the gastric mucosa but an increase in corpus mucin content was noted, whereas mucosal lesions appeared and the mucin content decreased in the duodenum in a dose-related manner. In the groups with histamine (0.8, 8, or 80 mg/kg intraperitoneally) administration, the extent of mucosal damage and the decrease in mucin content were dose-related in both these regions. For assessment of the effect of tetragastrin on the protective action in gastroduodenal mucosa, changes in mucin content and mucosal damage with histamine (80 mg/kg) -induced injury were examined. Coadministration of tetragastrin prevented the gastric mucosal damage and inhibited the decrease in corpus mucin content. In the duodenum, tetragastrin aggravated the histamine-induced mucosal damage and did not inhibit the reduction of the mucin content. From the present results, the increase in gastric mucins induced by tetragastrin might be related to the protective effect of gastric mucosa against injury. Tetragastrin did not protect the duodenal mucosa, and histamine-induced injury occurring in this region would be aggravated by the increase in HCl secretion and the decrease in mucin content induced by tetragastrin.

Novel chiral aminophosphines, N,N-disubstituted diphenyl(1-amino-2-naphthyl)phosphines 4 were synthesized via nucleophilic aromatic substitution reaction on 1-methoxy-2-(diphenylphosphinoyl)naphthalene (1) by chiral lithium amides 2, followed by reduction of the phosphinoyl function. The new ligands were tested for their efficiency in the palladium-catalyzed allylic substitution of dimethyl malonate with 1,3-diphenyl-2-propenyl acetate and high asymmetric inductions up to 80%ee were observed.

The effect of leminoprazole ((+-)-2-[[2-(isobutyl-methylamino)benzyl]sulfinyl]-1H-benzimidazol e, NC-1300-O-3, CAS 104340-86-5), a new compound being developed as an inhibitor of the gastric mucosal proton pump (H+,K(+)-ATPase), on gastric mucus secretion was studied by a biochemical method measuring the gastric mucin content in rats. Oral administration of leminoprazole (30 mg/kg) strongly inhibited the hemorrhagic lesions induced by 60% ethanol containing 0.15 mol/l HCl (acid-ethanol) administered 1 h later. Leminoprazole significantly inhibited the acid-ethanol-induced reduction of the mucin content in the surface mucosa including the mucus gel layer, but no significant effect could be obtained on the reduction of mucin present in the deep layer of the corpus and antral mucosa. Leminoprazole given to rats not treated with acid ethanol accelerated the secretion of deep mucosal mucus and increased significantly the content of soluble mucus which was recovered from the gastric luminal contents to about 200% of control, but failed to produce any significant change in the mucus content present in the surface mucosal and the mucus gel layers. The effect of leminoprazole on gastric mucus secretion might contribute to healing the peptic ulcer diseases and may be involved in the cytoprotective mechanism of this drug.

The effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2 (1H)-quinolinon-4-yl]-propionic acid, OPC-12759, CAS 11911-87-6), an anti-ulcer agent developed to enhance defensive factors in the gastric mucosa, on gastric mucus secretion was studied by a newly developed biochemical method to measure the gastric mucus glycoprotein content in rats. 1 h after intraperitoneal administration, rebamipide did not produce a significant change in the intramucosal mucus contents (surface mucosal layer and deep mucosal layers of corpus and antral regions) but significantly increased the content of soluble mucus, which recovered from the gastric contents, to about 160% of the control value. Since rebamipide has been shown to increase the biosynthesis of prostaglandins, indometacin was administered to the rats prior to rebamipide administration to examine whether the increase in prostaglandin biosynthesis contributes to the rebamipide-induced increase in gastric mucus secretion. The increase in the soluble mucus was not altered by the pretreatment with indometacin, thus indicating that rebamipide per se has a potential to increase the gastric mucus secretion by a mechanism that is not mediated by the endogenous prostaglandins. The effect of rebamipide on the gastric mucus secretion might contribute to heal and to prevent the recurrence of peptic ulcer diseases as well as to maintain the homeostasis of the gastric mucosa.

SM-10661 [(+/-)-(cis)-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl] displayed marked in vitro inhibition of rabbit platelet aggregation induced by 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (alkyl-PAF), 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16-PAF), and 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine, with IC50, values of 5.50, 5.94, and 3.68 microM, respectively. It also inhibited alkyl-PAF-induced aggregation of human platelets with an IC50 of 3.00 microM, but it did not inhibit platelet aggregation induced by ADP, collagen, arachidonic acid, the thromboxane A2 agonist U46619, or the Ca ionophore A23187, at concentrations up to 400 microM. Furthermore, SM-10661 antagonized [3H]-C16-PAF binding to rabbit platelets competitively, with an IC50 of 1.0 microM. SM-10661 protected against alkyl-PAF-induced lethality in mice with an ID50 of 6.0 mg/kg intravenously or 24 mg/kg orally. In guinea pig, SM-10661 inhibited the alkyl-PAF (0.1 micrograms/kg)-induced increase in bronchial pressure, with an ID50 of 0.7 mg/kg intravenously or 15 mg/kg orally. Bronchial hyperreactivity to bombesin after the infusion of alkyl-PAF was also inhibited dose-dependently by the infusion of SM-10661, with an ID50 of 25 mg/kg. In addition, SM-10661 inhibited alkyl-PAF (0.01 micrograms/kg)-induced hypotension in rats, with an ID50 of 0.36 mg/kg intravenously or 33 mg/kg orally. SM-10661, when given orally, showed rapid absorption and good duration of pharmacological activity in rats and rabbits.

In our previous reports, low dose acid secretagogues caused increase in corpus mucus glycoprotein content in rats. This increase was not due to the direct action of protons. The present study was conducted to determine whether this increase has a mucosal function or not Rats were given histamine (0.8 mg/kg) intraperitoneally or tetragastrin (12 micrograms/kg) subcutaneously. One hour following the acid secretagogues administration, the animals were given 1 ml of 30, 40 or 50% ethanol orally and then sacrificed after one hour. Gastric mucus glycoproteins were isolated from the corpus region of stomach. The following results were obtained: 1) Histamine prevented the gastric mucosal damage and the decrease of corpus mucus glycoprotein content induced by 40% ethanol ingestion. 2) Tetragastrin prevented the gastric mucosal damage induced by 30 approximately 50% ethanol ingestion and the decrease of corpus mucus glycoprotein content induced by 40 approximately 50% ethanol ingestion. Based on these results, the increase of corpus mucus glycoprotein content induced by acid secretagogues has a mucosal function. Moreover, tetragastrin strengthened the mucosal defence together with acid secretion.

The electrical recovery characteristics of relatively small air gaps between 0.3 and 9 mm were determined using a two-pulse method. The first pulse was used to over-volt the gap and initiate the arc current. The second pulse was used to determine the recovery voltage of the gap. A plot of the recovery voltage with time was obtained by varying the time delay of the second pulse relative to the arc extinction time of the first arc, in the time range form 50 mu s to 100 ms. It is found that the recovery characteristics are independent of the electrode materials (Cu, Al , St) and the arc current in the range from 40 to 200 A. It is also found that the shorter gaps and the rod plane gaps recover their dielectric strength faster than the longer gaps and the sphere gaps, respectively. >

A virus was isolated from large cupped narcissus showing symptoms of mild mosaic collected in Chiba in 1967. The virus was readily transmitted by juice inoculation, but not by Myzus persicae. Among the tested plants of 46 species in 15 families, 36 species of 13 families, namely, Chenopodiaceae, Amaranthaceae, Aizoaceae, Caryophyllaceae, Cruciferae, Leguminosae, Violaceae, Umbelliferae, Solanaceae, Pedaliaceae, Cucurbitaceae, Compositae, and Amaryllidaceae, were found susceptible to the virus. Of these plants, Chenopodium amaranticolor, bean, tobacco (Bright Yellow), petunia and cucumber were considered to be usefull as differential host plants for the virus. The virus was proved to be transmitted also through seeds of soybean at a very high rate.An evidence of soil transmission was provided by a greenhouse test using soil which surrounded diseased narcissus and was infested with nematodes including Xiphinema americanum. Lots of 1 to 50 X. americanum sieved from soil in which infected petunia had been grown for 2 to 3 weeks were placed near the roots of potted healthy petunia and cucumber plants. After 6 weeks the virus was detected, by juice inoculation and serological tests in 6 of 11 petunia plants, and in all of 4 cucumber plants. No infection occurred in control petunia and cucumber plants grown in soil free from X. americanum.The virus in vitro withstood heating at 55°C for 10 minutes, but not 65°C, dilution to 2×103, but not 2×104, and 7 days of storage at 20°C, but not 14 days. The virus particles were found to be spherical about 25-30mμ in diameter.Antiserum prepared showed homologous precipitin tube titre of 1/64. By agar gel diffusion tests, the virus showed negative reaction to antisera to tomato black ring virus and arabis mosaic virus kindly sent from Dr. B.D. Harrison and to tobacco ringspot virus antiserum kindly sent from Dr. R. Stace-Smith. The tomato ringspot antiserum obtained from Dr. R. Stace-Smith only gave positive result. The virus and the antiserum were furthermore sent to Dr. B.D. Harrison, and the above result was confirmed, along with an additional negative result with antiserum to strawberry latent ringspot virus.From these results, the virus was identified as tomato ringspot virus, which has not been reported before in Japan.Symptoms caused by this virus in narcissus is not marked. Virus-free narcissus seedlings that were juice inoculated, remained symptomless carriers for 17 months.

Solutions of phenylephrine hydrochloride at concentrations of 1, 2 and 5% were instilled in one eye of 5 normal volunteers. Both eyes were photographed concurrently with an infrared film, and the pupil diameter was determined by an image analyzer using the developed film. The mydriatic effects were expressed by the difference in the pupil diameter of the experimental and the fellow control eyes determined concurrently. The mydriatic effects with these 3 solutions reached a peak about one hour and 15 minutes after instillation; the peak effects and the logarithm of the drug concentrations showed a linear relationship. An extrapolation of the relationship gave a least effective concentration of 0.07%. From the time course of the mydriatic effects, the pharmacokinetic coefficients were calculated using a computer. The average values were 0.24 +/- 0.08 hour for the time lag of the mydriatic response to appear, 1.31 +/- 0.19 hour-1 for the apparent elimination rate constant and 1.47 +/- 0.28 hour-1 for the apparent absorption rate constant.

Fourty-four patients with advanced non-small cell cancer of the lung were treated with a combination chemotherapy of mitomycin C, endoxan, and cisplatin (MEP). The overall response rate was 20%, with 9 partial responses. The median duration of response was 7 months. The overall median survival was 10 months. No significant difference was noted in survival time between PR and NC. MEP therapy seems to provide a relatively easy therapeutic approach in the treatment of advanced lung cancer with no associated renal toxicity or loss of hair.

Five patients with malignant pleural effusion were treated with intrapleural administration of ACNU. Three of 5 patients showed cytologically negative in the pleural fluid and the fluid was eliminated in two patients. In 5 patients, 200 mg of ACNU was injected into the pleural space and pharmacokinetic behavior was studied. The clearance curves of ACNU in pleural fluid were described by either one-compartment model or two-compartment model. The mean half life of slow phase was 0.75 hour. These results indicate that ACNU disappears rapidly from the pleural space after the intrapleural administration. The effect of ACNU on the pleura was studied histologically in rabbits. At a dose of 3mg per kg body weight, the mesothelial cells were swelling and small areas of cellular desquamation appeared over the pleural surface. With increase in dosage, these findings were more pronounced and in the submesothelial tissue there was edema as well as cellular infiltration. In rabbits given two injections with interval of one week, the pleura showed a stronger reaction than that produced by single injection.

Tetracycline has been used for the local treatment of malignant pleurisy ever since of Robinson (1972) reported its effectiveness. In this report, we try to elucidate possible mechanisms of action of this drug from the viewpoints of (1) pharmacokinetic analysis following intrapleural administration, and (2) pleural reaction. The results were as follows: (1) In 5 patients with malignant pleural effusion, 500 mg of doxycycline was injected into the pleural cavity and pharmacokinetic analysis was performed. The clearance curve of doxycycline in pleural fluid was described by either a one-compartment model or a two-compartment model. The mean half life of slow space was 33.3 hr, which suggested delayed excretion of this drug from pleural space. (2) The direct effect of doxycycline on pleura was studied in rabbits. At a dose of 10 mg per kg of body weight, the mesothelial cells became cuboid and contained vacuoles in their cytoplasma. With increasing dose up to 40 mg per kg, the changes in mesothelial cells were enhanced. In submesothelial tissue, edema and cellular infiltration were noticed. Three weeks later, normalization of mesothelium was observed, being followed by connective tissue proliferation. These findings may support the efficacy of tetracycline for local treatment of malignant pleurisy.

Fluorescein angiography was carried out in 150 glaucoma subjects. Among them 94 subjects were selected to evaluate the correlation between functional loss and the findings of fluorescein angiography in the optic disc. The intensity of fluorescence was assessed in the superficial reticular capillaries and radial epipapillary capillaries. Functional loss was estimated by the visual field defects and cup-disc ratio. A marked decrease in the capillaries was seen in accordance with the increase in the cup-disc ratio. Also, the intensity of fluorescence in the optic disc paralleled the change in the visual field: the greater the deterioration in the visual field, the fewer the capillaries in the optic nerve head and vice versa. The fluorograms of 94 subjects were placed in one out of six groups, i.e. (1) normal, (2) arcuate scotoma, (3) superior or inferior nasal defects, (4) superior or inferior defects, (5) central residue or (6) temporal residue. The common factors correlating the fluorescein angiography in the glaucomatous optic disc with visual field loss were explored in 94 subjects, and it was possible to predict the visual field change from the capillary distribution in the glaucomatous optic disc.

The chemical and immunological properties of the protein of cucumber green mottle mosaic virus, watermelon strain (CGMMV-W), are presented. Amino acid analysis, amino-terminal residue (acetylalanine), and carboxyterminal amino acid (alanine) indicate that CGMMV-W is chemically related to cucumber virus 4 (CV-4). The serological relationship of CGMMV-W to CGMMV-C (cucumber strain), TMV-OM (common strain), and TMV-T (tomato strain) was confirmed by reciprocal tests. Heterologous reactions showed different degrees of serological relationship among the four strains. CGMMV-W was found to be more closely related to TMV-OM than to CGMMV-C and TMV-T. The partial amino acid sequences, containing residues 91–122, of CGMMV-W protein were determined and compared with those of other TMV or CGMMV proteins. Fifteen out of 32 amino acids were common to the CGMMV-W and TMV-OM proteins. We think it is high enough to consider that CGMMV-W has an ancestral relationship to TMV.