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Controlling hypertension has been revealed to be as important as controlling hyperglycemia to prevent the progression of diabetic nephropathy. Home blood pressure (HBP) measurement is useful for the treatment of hypertension. This study aimed to determine whether HBP measurement is a stronger predictor of the progression of diabetic nephropathy than clinic blood pressure (CBP) measurement. A multicenter follow-up study was performed at the Japan National Hospital Organization. A database of type 2 diabetic patients was constructed. In addition to CBP measurement patients, those using HBP were included in the database. Fifty-four patients with diabetic nephropathy were extracted from the database and analyzed. The rate of decline of the estimated glomerular filtration rate (eGFR) was calculated as the outcome. Correlations between the rate of eGFR decline and various clinical and laboratory parameters, including HBP and CBP measurement, were analyzed. The white-coat effect and reverse white-coat effect were frequently observed. The rate of eGFR decline correlated significantly with home systolic blood pressure (HSBP) measurement, but not with clinic systolic blood pressure (CSBP) measurement. Stepwise multiple linear regression analysis was performed. The rate of eGFR decline was significantly explained by the morning HSBP reading. The rate of eGFR decline was also significantly explained by the average of the morning HSBP readings during the follow-up period, the eGFR and age at baseline in the model, which included CBP and HBP measurements during the follow-up period instead of those at baseline. Home blood pressure measurement is useful for predicting the prognosis of diabetic nephropathy.

The quality of whiskey is known to improve remarkably by its storage over many years. This process is commonly termed "maturing." In this process, polyphenols derived from lignin and tannin of the barrel have an important role in not only forming the matured flavor and taste but also contributing to the advance of clustering ethanol and water in whiskey. It is also likely that polyphenols generally possess reactive oxygen (RO) scavenging activity. The present study evaluated the RO scavenging activity (free-radical scavenging activity, H(2)O(2) reduction activity under peroxidase coculture, and H(2)O(2)scavenging activity) of 24 single malt whiskeys with a maturation age of 10 to 30 y produced in Japanese, Scotch (Islay), or Scotch (Speyside and Highland) regions. Single malt whiskey not only showed RO scavenging activity but there was also a positive correlation between this activity and the maturation age of whiskey exceeding the difference resulting from the manufacturing region. A nonvolatile fraction derived from the barrel was responsible for RO scavenging activity. In particular, the contents of ellagic and gallic acids and lyoniresinol, the main polyphenolic compounds in whiskey, increased with maturation age. For the free-radical scavenging activity per molecule, each compound was 1.68 to 3.14 times that of trolox (a water-soluble vitamin E). The activities of ellagic acid, gallic acid, and lyoniresinol in the whiskey (Yamazaki 18) were equivalent to that of 80.3, 31.2, and 11.1 ppm trolox, respectively. Accordingly, the total activity of these 3 compounds accounted for about 20% of the activity of the whiskey (630.7 ppm trolox).

The universal primer sets for identification of human adenovirus (HAdV) targeting hexon gene were designed and applied to 121 clinical samples suspected of HAdV infection. The primer sets amplified at least 20 HAdV reference strains of six species. Of these clinical samples, 81 (66.9%) samples were positive for HAdV. They were classified into 11 serotypes belonging to 5 HAdV species (B-F). The primer sets described here are sensitive and reactive to the broad spectrum of HAdV and are useful for rapid diagnosis of various HAdV infections.

A 24-year-old female presented with Terson syndrome secondary to bilateral ventricular hemorrhage as a complication of moyamoya disease. Ophthalmoscopy and magnetic resonance imaging clearly demonstrated vitreous hemorrhage in the left eye globe. Various visual symptoms are associated with moyamoya disease, almost all of which result from ischemic lesions in the visual cortex and optic pathways. In this case, the visual disturbance was caused by Terson syndrome secondary to ventricular hemorrhage. Close ophthalmological and radiological evaluation is mandatory even in patients with moyamoya disease and hemorrhagic manifestation located in the intracerebral, subarachnoid, or intraventricular space.

The search for components exhibiting antioxidant activity in Ume liqueur, Japanese traditional liqueur made by steeping Ume (Prunus mume) fruit and sugar in spirits, was investigated. The active components were extracted more effectively by relatively polar solvents, such as ethyl acetate, diethylether and chloroform than nonpolar solvents. such as n-hexane and petroleum ether. Ethyl acetate extract from Ume liqueur was purified with solvent fractionation followed by Amberlite XAD-2, Wakogel C-100, Sephadex LH-20 column chromatographies and high performance liquid chromatography. The purified compound exhibiting antioxidant activity was identified as aryltetralin lignan, Lyoniresinol, by UV, EIMS, 1H-NMR and 13C-NMR spectra. Lyoniresinol suppressed linoleate autooxidation more effective than a-tocopherol at 72 hr incubation in the presence of 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH). These results suggest that habitual drinking of Ume liqueur possibly suppress lipid pe

A 67 year-old male who had suffered from myocardial infarction, was admitted to our clinic to examine his internal carotid artery stenosis revealed by preoperative study for heart surgery. Although he had no neurological symptoms, the angiograms showed severe stenosis of his right internal carotid artery. To improve stenotic internal carotid artery, PTA was performed employing a self-expanding stent. The stenotic right internal carotid artery was improved from 75% to 11% immediately after the stenting though restenosis mildly occurred up to 16% three months later. No complication occurred during this stenting procedure. Afterwards the patient uneventfully received coronary artery bypass grafting (CABG) surgery.

When a ground-fault problem occurs on a 6.6 kV power distribution line, it is essential to locate the fault point immediately and restore power to that line as soon as possible. However, in a combined system of both insulated wires and cables, surge signals could be affected by attenuation and reflection at both connected points and branch points, making an accurate determination of the fault point more difficult. Moreover, the surge signals of a 6.6 kV ungrounded power line are smaller than those of an ultra-high voltage grounded power line, further making it difficult to detect surge signals. Therefore, we have developed the fault location system and conducted verification tests on a fault locator on a 6.6 kV power distribution line. The ground-fault point is detected by measuring surge voltage propagation at both ends of line utilizing both noncontact voltage sensors and GPS (Global Positioning System) synchronizing technology. We found it important to acquire the first arrival surge and determine the surge traveling speed. These two points are key factors in improving the accuracy of the fault locator. First of all, as the power line produces much base noise, we have difficulty acquiring the first arrival surge. To solve this problem, we succeeded in developing a differential amplifier which improved the S/N (Signal /Noise) ratio. Secondly, we have established a method of calculating the fault point and the surge traveling speed from the switching surge in the combined insulated wire and cable system. In conclusion, we have conducted verification tests, enabling us to detect the fault location with an error rate ranging from 278 m to 363 m (3%) at a distance of 12.258 km. We are continuing work to improve the system.

The remodelling of the adipose tissue by pioglitazone may be associated with the sustained therapeutic effects. We studied the effects of withdrawal of pioglitazone after 3-month treatment on glucose, lipid and high-molecular weight (HMW) adiponectin levels as well as liver function in patients with type 2 diabetes mellitus.Forty-nine Japanese patients with type 2 diabetes mellitus were randomly assigned into the withdrawal group after 3-month treatment with pioglitazone (15 or 30 mg daily) and the non-withdrawal group.Three-month treatment with pioglitazone improved glycaemic control, homeostasis model assessment for insulin resistance (HOMA), dyslipidaemia and liver function tests in association with a marked increase in serum HMW adiponectin level. Three months later after the withdrawal of pioglitazone, however, fasting plasma glucose and HOMA increased, whereas serum HMW adiponectin decreased to the pretreatment levels. Dyslipidaemia also returned to the pretreatment level. On the other hand, liver enzymes at 3 months after the withdrawal remained lower after a mild rebound. In addition, the bone formation marker, serum bone-specific alkaline phosphatase, was significantly reduced by pioglitazone treatment in post-menopausal women.The present study suggests that 3-month treatment with pioglitazone has no sustained beneficial effects except in liver function tests in patients with type 2 diabetes mellitus.

We have found that the low immune response to streptococcal cell wall Ag (SCW) was inherited as a dominant trait and was linked to HLA, as deduced from family analysis. In the present report, HLA class II alleles of healthy donors were determined by serology and DNA typing to identify the HLA alleles controlling low or high immune responses to SCW. HLA-DR2-DQA1*0102-DQB1*0602(DQw6)-Dw2 haplotype or HLA-DR2-DQA1*0103-DQB1*0601(DQw6)-DW12 haplotype was increased in frequency in the low responders and the frequency of HLA-DR4-DRw53-DQA1*0301-DQB1*0401(DQw4)-Dw15 haplotype or HLA-DR9-DRw53-DQA1*0301-DQB1*0303(DQw3)-Dw23 haplotype was increased in the high responders to SCW. Homozygotes of either DQA1*0102 or DQA1*0103 exhibited a low responsiveness to SCW and those of DQA1*0301 were high responders. The heterozygotes of DQA1*0102 or 0103 and DQA1*0301 showed a low response to SCW, thereby confirming that the HLA-linked gene controls the low response to SCW, as a dominant trait. Using mouse L cell transfectants expressing a single class II molecule as the APC, we found that DQw6(DQA1*0103 DQB1*0601) from the low responder haplotype (DR2-DQA1*0103-DQB1*0601(DQw6)-Dw12) activated SCW-specific T cell lines whereas DQw4(DQA1*0301 DQB1*0401) from the high responder haplotype (DR4-DRw53-DQA1*0301-DQB1*0401(DQw4)-Dw15) did not activate T cell lines specific to SCW. However, DR4 and DR2 presented SCW to CD4+ T cells in both the high and low responders to SCW, hence the DR molecule even from the low responder haplotype functions as an restriction molecule in the low responders. Putative mechanisms linked to the association between the existence of DQ-restricted CD4+ T cells specific to SCW, and low responsiveness to SCW are discussed.

The purpose of this paper is to analyze the traffic flow characteristics under congested conditions on the intercity expressway, especially an accordion-like action, and the maximum flow rate at the bottlenecks. To analyze the relationshipsbetween speed characteristics and geometric factors is also another one of the objectives of this paper.In the first part of this paper, the authors discussed traffic phenomena of the congested flows up- and downstream of the bottlenecks, and clarified the accordion-like actions also appeared in the intercity expressway same as the urban expressways. In the middle part, characteristics of thefree speed at each detector station and lane were analyzed. In the last part, a multivariate analysis is applied to quantify the affects of the geometric factors to the free speed.

Between October and December, 2006, high activity of three genetically distinct norovirus GII-4 subtypes was observed in Chiba prefecture, Japan. One subtype was newly identified in this period and it was detected in 85% of outbreaks.

Control-flow diagrams are often criticized as difficult to read because of numerous edge intersections. To improve the readability we propose a solution that manages the visual complexity of graphs with hundreds, or even thousands of nodes. It consists in applying heuristics to choose the best path for an edge and an appropriate color that will help distinguish an edge from its neighbors.

One major challenge with graph-based visual languages is managing the complexity and maintaining a good readability as the density of edges in the graph increases. To improve the graph readability we propose a solution that manages the visual complexity of graph-based diagrams with many hundreds, and even thousands of nodes. It consists in applying heuristics to choose the best path for an edge and attributing to it a color defined automatically according to its origin and destination nodes. A grid system where certain areas are reserved for the display of nodes and others for the edges, is used for the layout of the nodes and edges.

We compared the results of EPBD in 18 patients using one-step catheter (one-step group) with those in 46 patients using usual two-step catheter (two-step group). The frequency of endoscopy and bile duct clearance were the equal in both groups. Pancreatitis occurred in only one patient of two-step group. Elevations of the amylase values were the equal in both groups. Amylase values after EPBD tended to decrease in 11 patients whose amylase values were above 500 IU/l before EPBD. Using one-step catheter in EPBD was useful for removing common bile duct stones easily and safety.

We herein report a rare case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and diabetes mellitus with ketoacidosis. An 18-year-old female patient was diagnosed to have diabetes mellitus and insulin therapy was thereafter initiated. At 26 years of age, she was hospitalized for diabetic ketoacidosis, soon followed by a loss of consciousness, left-sided dysmetria, and ataxic speech. MELAS was diagnosed because of the presence of ragged red fibers in a muscle biopsy. At 33 years of age, she was admitted to our hospital because of ketoacidosis and partial status epilepticus. A blood gas examination revealed as follows; arterial pH, 6.88; bicarbonate, 2.1 mmol/l; base excess - 29.8 mmol/l. The serum level of glucose had also increased to 30 mmol/l. The serum levels of lactate and B-hydroxybutyrate were elevated to 11.4 mmol/l and 1,990 micromol/l, respectively. Ketoacidosis improved by fluid replacement and continuous intravenous insulin infusion. A brain MRI demonstrated hyperintensity areas on FLAIR images in the bilateral temporal lobes and the cerebellum. A proton MRS demonstrated the abnormal lactate accumulation in the bilateral temporal and occipital lobes. Since epileptic seizures are rare in patients with diabetic ketoacidosis, such seizures may indicate the existence of MELAS syndrome.

A 24-year-old female presented with Terson syndrome secondary to bilateral ventricular hemorrhage as a complication of moyamoya disease. Ophthalmoscopy and magnetic resonance imaging clearly demonstrated vitreous hemorrhage in the left eye globe. Various visual symptoms are associated with moyamoya disease, almost all of which result from ischemic lesions in the visual cortex and optic pathways. In this case, the visual disturbance was caused by Terson syndrome secondary to ventricular hemorrhage. Close ophthalmological and radiological evaluation is mandatory even in patients with moyamoya disease and hemorrhagic manifestation located in the intracerebral, subarachnoid, or intraventricular space.

We report herein the case of a 56-year-old woman who presented with repeated transient ischemic attacks (TIAs). Cerebral angiography revealed that the left redundant internal carotid artery (ICA) uncharacteristically curved medially. These findings were highly suggestive of an internal carotid artery aneurysm at the level between the first and second cervical vertebral bodies. The lesion was presumed to be difficult to access by the surgical procedure usually adopted in carotid endarterectomy. Thus, we decided to employ a modified vertical mandibular osteotomy. The operative view revealed that the lesion was atherosclerotic stenosis with ulceration, so carotid endarterectomy was indicated. This mandibular osteotomy not only provided us with wide, satisfactory exposure of the distal cervical internal carotid artery but also afforded good mandibular stability during the postoperative period.

We reported the preliminary results of percutaneous transluminal angioplasty (PTA) supported with a self-expanding stent (Wallstent) for the cervical internal carotid artery (i.c.) stenosis in 6 patients (7 lesions). All were male aged from 60 to 79 (mean 70.8). Three patients were symptomatic and 3 were asymptomatic. The procedure was attempted in patients with severe i.c. stenosis according to criteria of NASCET, ECST or ACAS studies and with high risk if carotid endarterectomy (CEA) were performed. In all cases, vascular access was from the femoral artery and angioplasty was performed without cerebral protection. Successful angioplasty was obtained in all cases with no mortality. Stenosis was improved from 82.7% (74-90%) to 17.4% (10-33%). Perioperative complications were seen in only one case with TIA during the postdilatation period, which was supposed to be due to a distal embolism. The preliminary results of PTA supported with self-expanding stent for severe i.c. stenosis were excellent. These results suggested that some patients with severe i.c. stenosis can be treated safely and effectively by stent-supported PTA. However, it is necessary to mark the indications clear and strict, and to follow up these lesions after the procedure, because of the possibility of perioperative ischemic complications and restenosis.

It is very important to make a prompt and accurate diagnosis and to commence pertinent treatment for patients suffering from acute cerebrovascular occlusive disease. Thirteen patients (mean age: 67.1 years) with basilar artery occlusion (BAO) were enrolled in this study. Dynamic computed tomography functional images (FID-CT) were analysed to determine whether this method could diagnose BAO in the acute phase. The functional images were categorized into 3 groups: (1) group A (n = 5) showed abnormalities on corrected mean transit time (cMTT) images and time-to-peak (TP) images in the territory of the posterior cerebral artery (PCA) and in the thalamus, (2) group B (n = 6) only showed abnormalities on TP images, and (3) group C (n = 2) had no abnormalities on either cMTT or TP images. The group C patients had poor time-density curves because of heart disease. Although the results may sometimes be false negative and this limitation should be kept in mind, FID-CT seem to be useful not only for defining patients who need angiography but also those who need thrombolytic therapy for acute BAO.

Control-flow visual languages are often criticized as generating diagrams that look like a spaghetti plate. In this paper, we describe a solution we implemented to manage the visual complexity of control-flow diagrams with a very large number of nodes. Our solution is based on subdividing the display window into a sort of grid, with some areas where mostly nodes are displayed and other areas where mostly edges are displayed.

We studied the influence of reperfusion on carrier and barrier functions of the blood-brain barrier after transient global ischemia in rats. We used iodine-125-labeled 3-iodo-alpha-methyl-L-tyrosine and carbon-14-labeled sucrose as tracers for studying carrier and barrier functions of the blood-brain barrier, respectively. Brain uptakes of these two tracers were measured in Wistar rats subjected to either 15- or 30-minute four-vessel occlusion developed by Pulsinelli and Brierly before recirculation for 3, 6, 24, 48, and 72 hours. Tracer (5 microCi) was injected intravenously in each rat 30 minutes before killing the animal. Following 15- or 30-minute ischemia, [14C]sucrose uptakes were significantly higher at 3 and 6 hours of reperfusion before recovery to control values after reperfusing for 24 to 48 hours in almost all brain regions. However, a rebound in radioligand uptake was significantly manifested in some sites at 72 hours after reperfusion (p < 0.05 to p < 0.01). Uptakes of 125I-3-iodo-alpha-methyl-L-tyrosine were brain site-dependent: significantly (p < 0.05) higher in cortex (3 and 48 hours after reperfusion) and thalamus (3, 6, and 48 hours after reperfusion) but significantly (p < 0.05 to p < 0.01) lower in striatum, cortex (72 hours after reperfusion), and midbrain (6, 24, and 72 hours after reperfusion). Because the [14C]sucrose uptake in brain was 10% lower than that of 125I-3-iodo-alpha-methyl-L-tyrosine, the change in absolute transport of the latter tracer was approximated to its brain uptake. The carrier and barrier functions of the blood-brain barrier should be evaluated separately. The radioligand 125I-3-iodo-alpha-methyl-L-tyrosine may serve as a useful tool to evaluate the carrier function of the blood-brain barrier after transient cerebral ischemia in rats.

We reported the existence of high and low responders to streptococcal cell wall antigen (SCW) in human population. To analyze the mechanism of low responsiveness to SCW at the cellular level, we previously established SCW specific CD4+ T cell lines. During the course of generation of a SCW specific CD4+ T cell line restricted by HLA-DQ from a low responder, we obtained autoreactive CD8+ CTLs. Once the CTL was established as a line (HYCD8), they proliferated in the presence of autologous monocytes and IL-2 without SCW. HYCD8 lysed autologous monocytes and EBV transformed B lymphoblastoid cell line (BLCL). This cytotoxic activity was specifically inhibited by an anti-HLA class I framework mAb and restricted by HLA-B specificity, as judged by killing activity against panel cells and HLA class I-transfected BLCLs. Although HYCD8 contained perforin in the cytoplasm, this HLA-class I restricted cytotoxicity was observed only in the presence of the supernatant of cultured PBLs which could not be replaced by known cytokines and their mixtures. The biological activity of the soluble factor for cytotoxic activity (SFCA) was purified in a single peak fraction by HPLC. Thus, HYCD8 down-regulated the proliferation of SCW specific CD4+ T cells through killing autologous APCs in SFCA dependent manner suggesting a unique immunoregulatory role of autoreactive CD8+ CTLs in immune responses.

The prevalences and risk factors of micro- and macroalbuminuria were surveyed in all 927 patients with diabetes mellitus who visited outpatient clinics in 27 hospitals in the Fukuoka prefecture on a designated day. The urinary albumin-creatinine ratio (UAI; mg/g Cr) of spot urine was determined in all patients except those with persistent macroproteinuria. The results were as follows: (1) The prevalences of microalbuminuria (UAI 30-299) and macroalbuminuria (UAI greater than or equal to 300) were 26% and 15%, respectively. (2) Hyperglycemia and high blood pressure synergistically increased the prevalences. (3) The independent risk factors of microalbuminuria were severities of retinopathy and neuropathy, duration of diabetes, blood pressure, and HbA1c, as determined by logistic regression analysis, although the explanation rate was low.

Quinolinic acid was first identified in uremic serum by use of gas chromatography/mass spectrometry. Quantification by selected ion monitoring revealed that the serum concentration of quinolinic acid was markedly increased in chronic hemodialysis patients, and that the acid could be removed by conventional hemodialysis. The serum concentration of quinolinic acid was weakly but significantly correlated with the serum uric acid concentration. Accumulation of quinolinic acid in uremic blood may be involved in the pathogenesis of anemia, suppressed immune system, and uremic encephalopathy.

The effects of early-stage diabetes on disposition and renal handling of cefazolin (CEZ) were investigated in streptozotocin-induced diabetic rats. Significant increase in renal clearance was found in the diabetic rats (88%) and a strong correlation was obtained between renal and systemic clearance; however, there was no change in the volume of distribution. The results suggest that systemic clearance was increased as the result of enhancement of urinary excretion rate. Unbound fraction of CEZ in plasma was also increased by 60% in the diabetic rats and the increase may be due to the increase in glycosylated protein and plasma-free fatty acids. The filtration clearance for free drug in diabetic rats, which was estimated as glomerular filtration rate, was increased by about 1.9-fold compared to the normal rats, but the secretion clearance did not change in the two groups. Since kidney hypertrophy was observed in the diabetic rats, filtration and secretion clearance for free drug were normalized by means of kidney weight. After normalization for kidney weight, the two parameters were significantly reduced, indicating that the true kidney functions were impaired under the diabetic state. The parameters for CEZ secretion, maximum velocity and Michaelis-Menten constant, were also reduced in diabetic rats, suggesting that proximal tubule cell functions for secretion were altered in the diabetic rats. These results suggest that systemic and renal clearance was apparently increased in early-stage diabetes, whereas true kidney functions were impaired.

The effects of enoxacin and its metabolite 4-oxoenoxacin on the disposition of theophylline were investigated in rats. Systemic clearance of theophylline was significantly decreased by approximately 40, 46, and 50% after oral coadministration of 25, 100, and 200 mg of enoxacin per kg, respectively. No significant changes in the volume of distribution of theophylline were observed. 4-Oxoenoxacin had no direct effect on theophylline disposition. Significant changes in urinary excretion of theophylline and its metabolites were observed. (i) Urinary excretion of unchanged theophylline was significantly increased in proportion to increases in enoxacin dosage. (ii) Decreases in renal clearance of theophylline and metabolic clearance of 1-methyluric acid and 1,3-dimethyluric acid were observed. (iii) The percent decreases in the metabolic clearance of 1-methyluric acid were dependent on enoxacin dosage. It is likely that enoxacin inhibits the elimination process, which depends on cytochrome P-450-mediated isozymes for N demethylation and oxidation, and that the capacity of the inhibitory effect of enoxacin is greater in the N-demethylation pathway than it is in oxidation.

The gene encoding an extracellular Rhizopus niveus aspartic proteinase I (RNAP-I) was introduced into Saccharomyces cerevisiae. The yeast cell carrying a plasmid containing the intact RNAP-I gene under the control of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene promoter of S. cerevisiae did not synthesize RNAP-I at all. On the other hand, when the intron of the RNAP-I gene had been removed from the gene in the plasmid, the cell secreted RNAP-I with high efficiency. Processing of the pro-sequence occurred at the same region of the pro-enzyme during cultivation as observed in the culture of R. niveus. Moreover, the promoter and the terminator of the original RNAP-I gene were found to be weakly functional in the yeast cell with respect to expression of the intronless RNAP-I gene, although the initiation and termination sites were heterogeneous. The effects of vector-types on the extracellular production of RNAP-I were also investigated.

A review is presented which covers recent development in the theory of electronic structure of molecules. The literature survey was concluded in December 1957. Recent studies on the He atom are treated first, then nonempirical theory of simple molecules. Various semiempirical theories of molecules are discussed next, and results of calculations of various molecular constants are then reviewed. 83 references. (T.R.H.)

Purothionin from wheat flour was chemically modified by acetic or succinic anhydride under specific conditions. The complete modification of all amino groups of purothionin caused a large change in the net charge of the molecule, leading to the loss of the toxicity to mice and yeast. The sole tyrosyl residue in purothionin was nitrated by tetranitromethane at neutral pH or iodinated by the lactoperoxidase method. The nitro- and diiodo-derivatives of purothionin showed considerably reduced toxicity. Based on these modification studies we conclude that the positive charges of lysyl residues have an important role in the interaction with the negatively charged cell surface, and that the emergence of the toxicity of purothionin depends on a certain state of the tyrosyl residue.

Physicochemical experiments were performed in order to get further evidence of the formation of complexes between iron-sulfur proteins and flavoproteins from spinach chloroplast and beef adrenal cortex electron-transfer systems. With both spinach and adrenal iron-sulfur protein-flavoprotein systems, characteristic difference circular dichroism (CD) spectra between the sum of CD spectra of the respective proteins and the CD spectrum of a mixture with a molar ratio of one to one were obtained in the visible and far-ultraviolet regions. By differential scanning calorimetry (DSC) measurements, ferredoxin and ferredoxin-NADP reductase were found to be stabilized against heat treatment upon mixing: (1) the apparent denaturation temperatures of ferredoxin and the reductase increased by about 18 and 5 degree C, respectively, and (2) the activation energy of the denaturation reaction increased by about 50%. These results lead to the conclusion that the iron-sulfur protein and flavoprotein from a tightly bound complex, and suggest that the complex formation alters both the environments of the iron-sulfur and flavin chromophores and the contents of the ordered structures, resulting in stabilization of the proteins.

When the effects of new antiinflammatory drugs, 2-carboxyphenyl-1-(4-chlorobenzoyl)-5-methoxy-2-methyl-indole-3-acetate (TB 219) and 2-[(2-carboxyphenoxy)carbonyl]phenyl-1-(4-chlorobenzoyl)-5- methoxy-2-methylindole-3-acetate (TB 220), were investigated in various experiments, the following results were obtained: 1. TB 219 and TB 220 showed remarkable inhibitory effects on carrageenin edema, ultraviolet erythema and adjuvant arthritis. Although TB 219 displayed almost equipotent or slightly more potent effect than those of indometacin and acemetacin, TB 220 was slightly less effective than these two reference drugs except for the therapeutic effect on adjuvant arthritis. 2. TB 219 and TB 220 inhibited the writhing syndrome induced by acetic acid and inflammatory hyperesthesia, and they provided a significant antipyretic activity. 3. Both drugs elicited almost negligible side effects in the gastrointestinal tract even after the repeated administrations. Especially, ulcerogenic activity of TB 220 was extremely weak. LD50's of both drugs are higher than that of indometacin in rats. 4. Both drugs elicited no appreciable changes in general behavior in mice and rats after oral administration. After intraperitoneal or intravenous injection of these two drugs, no marked changes in spontaneous EEG pattern and the spinal reflex were observed.

The effect of purothionin, a peptide isolated from wheat flour, on adrenal medullary cells was examined in perfused bovine adrenal glands. Addition of purothionin (4 microgram/ml) to the perfusion fluid caused the release of cytoplasmic glutamic oxaloacetic transaminase (c-GOT), DOPA decarboxylase (DDC) and magnesium ions, which are present in the cytoplasmic fraction of adrenal medulla, but not the release of dopamine-beta-hydroxylase (DBH) or mitochondrial glutamic oxaloacetic transaminase (m-GOT), which are located in the particulate fraction. These results suggest that purothionin makes small pores in the cytoplasmic membranes of bovine adrenal medullary cells, resulting in the leakage of the cytoplasmic proteins and ions from the cells.

A basic polypeptide, purothionin A, which selectively injures cells in the S phase was tested on A31 cells producing MuLV. Treatment with 10 μg/ml PA has a marked cytotoxic effect on contact inhibited A31 cells infected with Moloney murine leukemia virus (Mo-MuLV), but scarcely any effect on uninfected A31 cells. On the basis of this finding we developed a new method for titration of MuLV: Cultures infected with highly diluted MuLV, which showed no XC plaques, were not affected appreciably by purothionin A, whereas culture infected with low dilutions of MuLV, in which large numbers of XC plaques normally developed, were severely affected by purothionin A. The results of this assay method were consistent with those obtained by XC plaque assay.

Der Pantothensaureester (II) wird mit den Zuckerderivaten (I) nach den im Formelschema angegebenen einfachen Umsetzungen in die 4′-O-β-D- Glykoside (V) der Pantothensaure umgewandelt.