Characteristics of sensori-motor interaction in the primary and secondary somatosensory cortices in humans: a magnetoencephalography study.

We studied sensori-motor interaction in the primary (SI) and secondary somatosensory cortex (SII) using magnetoencephalography. Since SII in both hemispheres was activated following unilateral stimulation, we analyzed SIIc (contralateral to stimulation) as well as SIIi (ipsilateral to stimulation). Four tasks were performed in human subjects in which a voluntary thumb movement of the left or right hand was combined with electrical stimulation applied to the index finger of the left or right hand: L(M)-L(S) (movement of the left thumb triggered stimulation to the left finger), L(M)-R(S) (movement of the left thumb triggered electrical stimulation to the right finger), R(M)-R(S) (movement of the right thumb triggered electrical stimulation to the right finger), and R(M)-L(S) (movement of the right thumb triggered electrical stimulation to the left finger). Stimulation to the index finger only (S condition) was also recorded. In SI, the amplitude of N20m and P35m was significantly attenuated in the R(M)-R(S) and L(M)-L(S) tasks compared with the S condition, but that for other tasks showed no change, corresponding to a conventional gating phenomenon. In SII, the R(M)-L(S) task significantly enhanced the amplitude of SIIc but reduced that of SIIi compared with the S condition. The L(M)-L(S) and R(M)-R(S) tasks caused a significant enhancement only in SIIi. The L(M)-R(S) task enhanced the amplitude only in SIIc. The laterality index showed that SII modulation with voluntary movement was more dominant in the hemisphere ipsilateral to movement but was not affected by the side of stimulation. These results provided the characteristics of activities in somatosensory cortices, a simple inhibition in SI but complicated changes in SII depending on the side of movement and stimulation, which may indicate the higher cognitive processing in SII.

The spectrophotometric determination of trace molybdenum (VI) after collection and elution as molybdate ion on protonated chitin.

Collection and elution method for inorganic anion on protonated chitin has been applied to the spectrophotometric determination of molybdenum (VI). The molybdenum (VI) is collected as molybdate ion on a column of chitin in weak acidic medium which is easily eluted with a small volume of 0.1 M ammonia buffer solution (pH 10). The molybdenum (VI) in the eluent is determined by bromopyrogallol red-Zephiramine method spectrophotometrically. Beer's law is obeyed over the concentration range of 0.1-0.8 mug of molybdenum (VI) in 1 ml of eluent at 634 nm. The apparent molar absorptivity is 6x10(4) dm(3) mol(-1) cm(-1). The tolerance limits for WO(4)(2-), VO(3)(-), CrO(4)(2-) and Fe (III) is low, that is, 1-100 times that of molybdenum (VI), but some metal ions and common inorganic anions do not interfere in concentration range of 1000-5000 times that of molybdenum (VI). The present method can be applied to the determination of molybdenum (VI) in natural water samples.

The simple and rapid spectrophotometric determination of trace chromium(VI) after preconcentration as its colored complex on chitin.

Preconcentration method with collection of metal complexes on a chitin has been applied to the spectrophotometric determination of chromium(VI) in water. The chromium(VI) is collected as its 1,5-diphenylcarbazide(DPC) complex on a column of chitin in the presence of dodecyl sulfate as counter-ion. The Cr-DPC complex retained on the chitin is eluted with a methanol-1 M acetic acid mixture (7:3, v/v), and the absorbance of the eluent is measured at 541 nm. Beer's law is obeyed over the concentration range of 0.05-0.6 mug of chromium(VI) in 1 ml of the eluent. The apparent molar absorptivity is 3.5x10(4) dm(3) mol(-1) cm(-1). The tolerance limits for Fe(III) is low, i.e. ten times that of chromium(VI), but some metal ions and common inorganic anions do not interfere in concentration range of 100-10 000 times that of chromium(VI). The present method can be applied to the determination of chromium(VI) in natural water samples.

Preparation of Amberlite XAD resins coated with dithiosemicarbazone compounds and preconcentration of some metal ions.

The Amberlite XAD resins coated with dithiosemicarbazones were prepared and their collection behavior of metal ions from aqueous solution was investigated. Among the resins used, the reagent-loaded Amberlite XAD-7 was found to be superior for the collection of metal ions to other reagent-loaded resins used. The quantitative collection of mercury(II), palladium(II) and copper(II) was obtained from acidic medium, while cadmium(II) and lead(II) was obtained from neutral medium by the Amberlite XAD-7 resin coated with dimethylglyoxal bis(4-phenyl-3-thiosemicarbazone) (DMBS). These metal ions collected on the resin were easily eluted with a small volume of N,N-dimethylformamide as their DMBS chelates. This collection-elution method was applied to the determination of their metal ions by reversed-phase high performance liquid chromatography with a spectrophotometric detection.

Simultaneous determination of platinum(II) and palladium(II) by reversed phase high-performance liquid chromatography with spectrophotometric detection after collection on and elution from resin coated with dimethylglyoxal bis(4-phenyl-3-thisomicarbazone).

Amberlite XAD-7 resin coated with dimethylglyoxal bis(4-phenyl-3-thiosemicarbazone) (DMBS) was prepared and applied to the preconcentration of platinum(II) and palladium(II) from aqueous solution. Platinum(II) and palladium(II) were collected quantitatively on resin coated with the reagent (DMBS-XAD-7) from acidic solution in the presence of iodide ion by a bach method. The metal ions were then easily eluted from DMBS-XAD-7 as their DMBS chelates with a small volume of N,N-dimethylformamide. This collection and elution method was applied to the simultaneous determination of platinum(II) and palladium(II) by reversed-phase high-performance liquid chromatography with spectrophotometric detection using an ODS column and acetone-water as the mobile phase. The proposed method was applied to the determination of the metals in commercially available samples.

Electrochemical detection of lectin using a galactosamine labeled with daunomycin.

To detect a lectin from soybean, an electrochemical procedure was developed by the use of a labeling of galactosamine. Because the lectin has binding sites to galactosamine, galactosamine labeled with daunomycin having electroactivity was prepared. When labeled galactosamine (LG) combines with lectin, the part of daunomycin is taken in the binding sites of the lectin and becomes electroinactive. Therefore, the concentration of the lectin can be estimated by measuring the peak current of the LG. On the other hand, a competitive reaction to the lectin of galactosamine and the LG makes a detection of galactosamine possible. This method has merit that does not require a separation procedure of the free LG from the bound one. An effect of length of spacer between daunomycin and galactosamine was also investigated. It was found that adsorption of reagent on the electrode increased due to introduction of the spacer. Furthermore, the electrode response of the LG was influenced by the type of the spacer.

[Reproduction study of Guanabenz, a new antihypertensive agent (1) - fertility test in rats].

Guanabenz (WY-8678) was given to rats to examine its effects on their reproductive ability, dams and their fetuses. The drug was administered orally to rats at 30, 15, and 1 mg/kg/day. The vehicle used was 5%-Arabic Gum at dose level of 5 ml/kg, and a control experiment where only vehicle was administered was also conducted. Male rats were treated for 60 days before mating and the treatment continued through mating. Female rats were treated 14 days before mating and the treatment continued from mating to the 7th day of gestation. The results obtained were as follows. 1. In male rats before mating in the 30, 15, and 5 mg/kg groups, the increase of body weight tended to be suppressed, and decrease of food consumption and increase of water intake were found. In female rats before mating in the 30 and 15 mg/kg groups, increase of body weight tended to be repressed, and decrease of food consumption and increase of water intake were found in each group. 2. In the observation of males and females, the drug induced decrease in spontaneous movement, sedation, lacrimation of red exudate and nebula of the eyeball. 3. In the reproduction test, copulations were confirmed in almost all rats by the second cycle of matings. However, the pregnancy rate tended to decrease a little in the 30 and 15 mg/kg groups. 4. Body weight increase during gestation was not affected by oral administration of 1 mg/kg, but was inhibited dose-dependently by administration of more than 5 mg/kg/day of Guanabenz. Food consumption and water intake tended to increase in drug-treated groups. 5. In the observation of the fetuses, the average number of corpora lutea were decreased in the 15 mg/kg group. The average number of implantations decreased in the 30 and 15 mg/kg groups. The implantation rate decreased in the 30 mg/kg group. No difference was observed in each group on the number of resorptions, the number of live fetuses, and the sex ratio. 6. No difference was observed in each group as to external and visceral malformations. In the skeletal observation, retardation of ossification was observed in the 30 mg/kg group. From these results, it is concluded that Guanabenz shows neither fatal effect nor teratogenic potential on fetuses in rats and the safe dosage level seems to be below 5 mg/kg/day.

[Reproduction study of Guanabenz, a new antihypertensive agent (2) - teratological test in rats].

Guanabenz (WY-8678) was given to pregnant rats to examine its effects on dams, their fetuses, and offspring. The drug was administered orally to rats at 15, 5 and 1 mg/kg/day from the 7th days of gestation. The vehicle used was 5%-Arabic Gum at dose level of 5 ml/kg, and a control experiment where only the vehicle was administered was also conducted. The results obtained were as follows. 1. In the observation of the dams, the increase of body weight tended to be repressed in the 15 mg/kg group, and body weight decreased in the 30 mg/kg group. 2. The drug produced decreased spontaneous movement, sedation, and lacrimation of red exudate in dams. 3. Half of the 30 mg/kg group had a resorption, but there were no remarkable effects on length of gestation and nursing in the nursing group. 4. The weight of the thymus decreased dose-dependency. 5. No difference was observed in each group in the number of corpora lutea, the number of resorptions, the number of live fetuses, sex ratio, and mean placental weight of the fetuses. The mean body weight of the fetuses decreased in the 30 and among 15 mg/kg groups. 6. In observation of the fetuses, no difference was observed among groups regarding external and visceral malformations. In the skeletal observation, retardation of ossification of the forelimb and hind limb was observed in the 30 and 15 mg/kg groups, and retardation of ossification of the sternebra was observed in the 30 mg/kg group. 7. In observation of the offspring, the number of implantations, the number of live fetuses, delivery rate, and viability rate decrease in the 30 mg/kg group. No difference was observed among groups as to postnatal development symptoms, the faculties of sensation, and emotion. From these results, it is conducted that Guanabenz has no teratogenic potential in rats and the safe dosage levels seems to be below 5 mg/kg/day.

[Reproduction study of Guanabenz, a new antihypertensive agent (3) - perinatal and postnatal test in rats].

Guanabenz (WY-8678) was given to rats to examine its effects on dams and offspring in terms of influence on postnatal development emotion, learning and reproductive ability. The drug was administered orally to rats at 15, 8, 5, 2 and 1 mg/kg/day from the 17th day of gestation to the 21st post-partum day. The vehicle used was 5%-Arabic Gum at dose level of 5 ml/kg and a control experiment where only vehicle was administered was also conducted. The results obtained were as follows. 1. In observation of the dams, increase in body weight tended to be repressed after administration in the 8 mg/kg group, and in the 15 mg/kg group body weight decreased. Food consumption and water intake tended to be suppressed in the 15 mg/kg group. During nursing, changes of body weight, food consumption and water intake were not influenced by Guanabenz in each group. 2. The drug produced sedation, abnormal walking, decrease in a reflex test and lacrimation of red exudate in dams. 3. In the 15 mg/kg group, the length of gestation was prolonged. Furthermore, abnormal delivery and nursing were observed, and in one-third of dams in the 8 mg/kg group and in all dams of 15 mg/kg group, the still-birth of all offspring was observed. No difference was observed among groups as to the organ weights at weaning. 4. In observation of the offspring, differences were observed in the viability rate and the weaning rate. No difference was observed among groups as to the viability rate, changes of body weight, postnatal development, and behavioral development on the 7th day. No differences were observed in each group regarding emotion, motion, perception and learning. 5. No difference was observed among groups in the reproduction test. As to symptoms seen in gestation, the dams and fetuses were not influenced by dosage of Guanabenz. From these results, the safe dose level seems to be below 5 mg/kg/day.

[Reproduction study of Guanabenz, a new antihypertensive agent (4) - teratological test in rabbits].

Guanabenz (WY-8678) was given to pregnant rabbits to examine its effects on the dams and their fetuses. The drug was administered orally to rabbits at does of 10, 8, 5 and 1 mg/kg/day from the 6th to 18th days of gestation. The vehicle used was 5%-Arabic Gum at dose level of 10 ml/kg, and a control experiment where only the vehicle was administered was also conducted. The results obtained were as follows. 1. Concerning the effects on the dams, the symptoms of decrease in spontaneous movement and sedation were observed at 10 mg/kg. However, mean body weight, food consumption, and organ weight were not influenced by Guanabenz. 2. In the observation of the fetuses, no difference was observed among groups in the number of corpora lutea, the number of implantations, implantation rate, the number of resorption, the number of dead fetuses, the number of live fetuses, sex ratio, mean body weight of the fetuses, mean body length of the fetuses, and mean placenta weight of the fetuses. 3. No difference was observed among groups regarding external malformations, visceral malformations, skeletal malformations, skeletal variations and degree of ossification in the fetuses. From these results, it is concluded that Guanabenz has no teratogenic potential in pregnant rabbits and on effect no fetuses at doses of 8 mg/kg or lower.

[Mutagenicity test of antithyroid agent, methimazole--dominant lethal mutation test on male mice (author's transl)].

Mutagenicity test of Methimazole (MMI) was performed by means of dominant lethal mutation test in the male mice. Male mice were treated with a single s.c. injection of 45 mg/kg or 90 mg/kg MMI. Mean body weights were slightly decreased and mating rates were low immediately after treatment of MMI. Mean numbers of living implants at any periods examination up to 6 weeks after the treatment were compared with Salin Control, indicating lack of dominant lethality of MMI. On the other hand, EMS and MMC known mutagens and reference agents used in the present study, induced dominant lethalities at a single s.c. injection respectively.

Voltammetric detection of lectin using sugar labeled with electroactive substance.

The voltammetric detection of soybean agglutinin (SBA) was investigated on the basis of an interaction between the lectin and a sugar. Because galactose and lactose combined with SBA, the sugars were labeled by a Schiff base with an electroactive daunomycin. After the labeled sugar and SBA were mixed, measurements were carried out by voltammetry. When SBA-sugar binding occurs, a part of daunomycin of the labeled sugar is taken to the binding sites. As a result, SBA is detected by a change in the peak current of daunomycin, and the SBA-sugar interaction is evaluated. The length of the alkyl chain between daunomycin and the sugar was also considered. The electrode response to the concentration of SBA was linear over the range of 0.04-0.8 microg min(-1). The merits of this procedure are the convenient preparation of labeled sugar and a rapid measurement without separation. On the other hand, the detection of sugar at the 10(-9) mol dm(-3) level was achieved by a competitive reaction to limited binding sites of the lectin between the sugar and the labeled sugar.

[Clinical effects of cefoselis (CFSL) on infections in obstetric and gynecologic field and prevention of postoperative infections].

Clinical effects of cefoselis (CFSL) on various infections and prevention of postoperative infections in the field of obstetrics and gynecology were investigated with a total of 100 patients of 8 facilities in Yamagata and the following results were obtained: 1. For the patients (n = 70) who received the treatment with CFSL at 2 g/day for 5 days to prevent postoperative infections, the treatment was effective for such infections in 68 of 69 (98.6%) except one to whom the treatment was discontinued during the course. 2. For the patients with infections (n = 30) who were treated with CFSL at 2-4 g/day for 5-7 days, the treatment was markedly effective in 8/30 (26.7%), effective in 21/30 (70%) and not effective in 1/30 (3.3%). The overall rate of efficacy was 29/30 (96.7%). Based on the clinical effects for each isolate, the bacteriological efficacy was evaluated as 29/29 and the rate of bacterial eradication for each isolate was 23/29 (79.3%). 3. Laboratory test revealed liver functional abnormalities in one patient and eruption, a subjective/objective symptom caused by CFSL was noted in two patients. These results suggest that CFSL is effective for various infections in obstetric and gynecologic field and also the prevention of postoperative infections.

[Clinical studies of faropenem in the field of obstetrics and gynecology].

The clinical effect of faropenem was evaluated in 165 ambulatory patients with various infections in the field of obstetrics and gynecology at 10 institutions in Yamagata Prefecture. The results obtained are summarized below. 1. The rate of efficacy, as determined from the clinical effect following 3- to 7-day repeated administration at a dose of 600 mg/day, was 97.9% (46/47) for intrauterine infections, 92.0% (23/25) for adnexitis, 93.8% (15/16) for external genital infections, 88.9% (8/9) for mastitis, 94.0% (63/67) for cystitis, and 100% (1/1) for cervicitis. The overall efficacy rate was estimated to be 94.5% (156/165). 2. The rate of clinical efficacy, as classified by isolate, was high, 95.1% for Gram-positive bacteria, 100% for Gram-negative bacteria, and 100% for anaerobes. As for bacteriological response classified by isolate, the eradication rate was high, 91.4% (74/81) for Gram-positive bacteria, 98.4% (62/63) for Gram-negative bacteria, 89.5% (17/19) for anaerobes, and 93.9% (153/163) in all. 3. No adverse reactions or laboratory abnormalities were observed in any patient. The results presented suggest that faropenem is a highly safe and effective antibiotic for the treatment of obstetric or gynecological infections of various kinds in an ambulatory setting.

[Structure and assembly of human beta herpesviruses].

This review is concerned with the structure and assembly of HCMV, HHV6 and HHV7. A characteristic ultrastructural feature common to all these viruses is a distinct tegumentary coating of intracytoplasmic capsids. The tegument structure is also distinctly seen in the virions of HHV6 and HHV7. Morphologically, acquisition of the tegument was observed to have taken place in the cytoplasm. Immunoelectron microscopic studies of HCMV infected cells, however, have demonstrated the existence of a tegument protein, pp150, on the surface of intranuclear capsids as well as on capsids in the cytoplasm and in extracellular virions. In addition, another tegument protein, pp65 has been detected within the matrix of cytoplasmic and extracellular dense bodies but not in virions. The molecular mechanism of the assembly of beta herpesviruses was also discussed.

Pharmacological studies of imidazoline derivatives. II. Agonistic and antagonistic actions on alpha-adrenoceptors in various smooth muscle preparations.

The effects of 8 imidazoline derivatives on alpha-adrenoceptor-mediated contraction or relaxation of various kinds of smooth muscle preparations were investigated. In rabbit aortic strips, K-6341, K-6343 and K-4011 produced alpha-agonistic action which was antagonized by prazosin. In the study of alpha-antagonistic action of imidazoline derivatives, i.e. antagonism against norepinephrine- or phenylephyrine-induced contraction of the rabbit aortic strip, the order of potency series, prazosin greater than phentolamine greater than yohimbine greater than K-4011, K-3827, K-4300 greater than tolazoline was found. Reserpine pretreatment did not affect the results. In the study of alpha-antagonistic effect on the relaxing response to norepinephrine of methacholine-contracted rat ileum, the potency series was revealed as follows: prazosin greater than phentolamine greater than yohimbine greater than K-4011, K-3827, K-4300, tolazoline. A similar experiment was performed on histamine-contracted guinea-pig taenia coli, and the results were nearly identical to the case of the rat ileum, except that K-6341 and K-6343 also exhibited alpha-antagonistic action which was not detected in the rat ileum. This suggests that alpha 2-receptor may exist in the postsynaptic alpha-adrenoceptor in the guinea-pig taenia coli. The results of the present study indicate that the potency of imidazoline derivatives to inhibit norepinephrine-induced contraction of some smooth muscle is almost identical to that which inhibited norepinephrine-induced relaxation of other smooth muscles. Furthermore, K-4300 was found to possess anti-acetylcholine and anti-histamine actions in the guinea-pig taenia coli and anti-serotonin action in the rat fundus strips.

Pharmacological studies of imidazoline derivatives. III. Actions on cardiovascular system and acute toxicity.

The effects of 8 imidazoline derivatives on the cardiovascular system and their acute toxicity were investigated. In anesthetized rats, K-6341 and K-6343 produced relatively long-lasting elevation of blood pressure. This hypertensive response was prevented by prazosin. In contrast, K-4011, K-3827 and K-4300 exerted long-lasting hypotensive actions. Norepinephrine-induced increase in blood pressure was competitively antagonized by these three derivatives. Therefore, the hypertensive and hypotensive actions of imidazoline derivatives are conceivably exerted by activating and blocking alpha 1-adrenoceptors. In the isolated guinea-pig atrial preparations, K-4011, K-3827, K-6341 and K-6343 produced positive inotropic responses which were independent of beta-adrenoceptor activation. The positive inotropic effect of K-6341, which was the most potent, was specifically attenuated or abolished by diltiazem, suggesting that a change in Ca2+ movement across the cell membrane is contributing to K-6341-induced increase in atrial contractions. The main symptoms of mice manifested when injected with imidazoline derivatives were a decrease in spontaneous movement, exophthalmos, an increase in palpebral opening, paralysis of four limbs and respiratory depression. Acute LD50 values of imidazoline derivatives in mice (i.v., i.p.) were between these of tolazoline and naphazoline.

Pharmacological studies of imidazoline derivatives. I. A comparison of the effect on pre- and postsynaptic alpha-adrenoceptors in the rat vas deferens.

The effects of 8 imidazoline derivatives on pre- and postsynaptic alpha-adrenoceptors and [3H]norepinephrine release were investigated in the rat vas deferens and were compared with those of reference drugs, yohimbine, phentolamine, tolazoline, and prazosin. K-6341 and K-6343 activated postsynaptic alpha 1-adrenoceptor and were antagonized by prazosin. The order of potency series as alpha 1-antagonist, prazosin greater than phentolamine greater than yohimbine greater than K-4011 greater than K-3827 greater than K-4300, tolazoline was found in antagonism against phenylephrine. Many derivatives exhibited an antagonistic action against clonidine, and the potency series as alpha 2-antagonist was revealed as follows: phentolamine greater than yohimbine greater than K-3827 greater than K-4011 greater than K-6341 greater than K-6343 greater than K-4300, tolazoline greater than prazosin greater than K-4299. The antagonistic effect was more selective on presynaptic (alpha 2) than postsynaptic (alpha 1) adrenoceptor and the rank order of selectivity (KB-post/KB-pre) was K-3827 greater than yohimbine greater than K-4011 greater than tolazoline, K-4300 greater than phentolamine greater than prazosin. Imidazoline derivative increased [3H]norepinephrine release, the actions of K-3827, K-6341 and K-4300 being particularly potent. From these results, the structure-activity relationship was summarized. First, when 2',3'-methylenedioxyphenyl group is connected with the imidazoline ring via an amino or methylene residue, these compounds become alpha 1-agonist. Secondly, when the methylenedioxyphenyl group and the imidazoline ring are connected via an amino residue, these compounds show a weak agonistic and potent antagonistic characteristics at the presynaptic alpha 2-adrenoceptor. Thirdly, an addition of a methylenedioxy radical to the phenyl ring increased the affinity of the compounds to presynaptic alpha 2-receptor.