Using specimens of tracheal muscle excised from guinea pigs, the effects of aminoglycoside antibiotics on the action of anti-asthmatics and adrenergic agents were studied. Using chain specimens of excised trachea obtained from guinea pigs of the Hartley strain (250-300mg), contraction and relaxation of tracheal muscle were recorded on Kymograph smoked paper (with a frontal stylo) . As agonist, Ach 1×10^-6, His 3×10^-6and Bac 1₂1×10^-3were used and five aminoglycoside antidiotics were selected for use, namely, gentamicin, amikacin, kanamycin, streptomycin and tobramycin Three macrolide antibiotics such as erythromycin, spiramycin and leucomycin and two polypeptides such as colistin and colistin methane sulfonate, as well as chloramphenicol, ampicillin and cefazolin were also used here. Here, also, five adrenergic agents such as isoproterenol, adrenaline, noradrenaline, ephedrine and salbutamol were employed. As steroid, we used hydrocortisone sodium succinate, all as anti-asthmatic agents. ED₅₀'s by three agonists were ; Ach=3×10^-8> His=3 × 10^-6> Bac l₂=3×10^-4. Abatement due to antibiotics was noted to be the strongest with aminoglycosides and no great difference was observed between macrolides and polypeptides. Among aminoglycosides, gentamicin showed the strongest effect. Among the macrolides, the effect of leucomycin was the strongest, but similar effects were also observed with chloramphenicol, etc. The ED₅₀'s of the five adrenergic agents were obtained, and the comparison of their potencies revealed Ach contraction in the order of isoproterenol=2×10^-8> Salbutamol=5×10^-9> adrenaline =6×10^-8> noradrenaline =2×10^-6> ephedrine =1×10^-4. In the case of Bac l₂, the strongest was salbutamol and, in the case of His, salbutomal and isoproterenol were nearly on the same level of potency. In combined use of adrenergic agents with antibiotics, when Ach was used as agonist, the augmentation effect was below 20%, except for ephedrine, and when His was used, the percentage of augmentation were 11-40 % with salbutamol and 47-87 % with others. When Bac l₂was used, the percentages were 60-82 % in the case of concomitant used with ephedrine and 56-81% with others. Hydrocortisone showed no marked effect against agonists in delayed action of post-treatment. In case of pretreatment being used together with antibiotics, abatment was augmented. Potency was found in the following order: kanamycin ampicillin cefazolin.

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We have studied the teratogenicity of centrifugal forces on embryonic cardiovascular systems in chick embryos. Environmental factors may play a teratogenic role in modern life and this study was undertaken to help elucidating the possible causes. Fertile white leghorn eggs, weighing 58 g on the average, were obtained from a commercial hatchery in Tokyo ; they were incubated at 38°C until the embryos reached developmental stages 22 to 40 somites of Hamburger-Hamilton (approximately 3-4 days) . Experimental groups corresponding to this developmental age were placed in a centrifuge. An automatic high-speed refrigerated centrifuge, 20 PR-52-type, was used to centrifuge the fertilized eggs, warmed to 30°C and set in 500 pp tubes around the RP-RS 3-3 swing rotor. Fertilized eggs were subjected to centrifugation at 500 rpm for 5 to 10 minutes or 1000 rpm for 5 to 10 minutes. The mortality rate and resulting congenital malformations of the cardiovascular system were higher in the experimental group compared to the control (p <0.001) . Extracardiac anomalies such as body torsion, skull asymmetry, skull or mandible anomalies and/or cyclopia were encountered. The application of centrifugal force induced double outlet right ventricle (DORY), ventricular septal defect (VSD) and hypoplastic right ventricle. Ectopia cordis with complex cardiovascular anomalies was also analyzed. Our study is very specific on the induction of complex cardiovascular anomalies depending on the various degrees of centrifugal force applied during organogenesis. The possible mechanism involved in the genesis of various malformities in this experiment may be explained as abnormal physio-hemodynamic effects caused by centrifugal force on the primitive flow pattern in embryonic chick hearts and on the development of the thoracic abdominal system.

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The minimum inhibitory concentrations of anthramycin for gram-positive bacteria were 0.78-3.12μg/ml, and for gram-negative rods, 25-50μg/ml or more than 100μg/ml. Marked prolongation of life span was observed by the intraperitoneal injection of 0.075 or 0.15mg /kg/day of anthramycin for 4 days in mice transplanted intraperitoneally with leukemia P 388. A dose of 0.008 or 0.04 mg/kg/day for 5 days was effective against ascitic forms of sarcoma 37 and sarcoma 180. When mice were intraperitoneally injected with anthramycin, 0.25 mg/kg once, before immunization with sheep red blood cells (on day -4 or -2), the number of plaque-forming spleen cells (PFC) was markedly decreased. On the contrary, when treated with anthramycin, 0.125 or 0.25mg/kg intraperitoneally once, on day 0 or +1, PFC was remarkably increased. In the intravenous route of administration, increase in PFC was recognized, even by pretreatment with anthramycin (0.25mg/kg on day -4) . The delayed-type cutaneous hypersensitivity with picryl chloride in mice was significantly inhibited by treatment with anthramycin before or after sensitization.

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In our laboratory, we found that 1) after treatment of D-phenylalanine (DPA), or lesion of the analgesic inhibitory system, the lateral centromedian nucleus of the thalamus (ICM), acupuncture non-point stimulation caused analgesia, which is quite different from acupuncture point stimulation-produced analgesia (AA) and that 2) after treatment with DPA, the individual variations in effectiveness of AA disappeared. In the present experiment, the relationship between DPA action and lesion effect of ICM has been investigated and the effect of DPA on naloxone reversal AA has been studied as well. After lesion of the lateral septum (lSp), which is the site of AA-producing afferent pathway (R₂) from the acupuncture point to the hypophysis, AA disappeared. Under these conditions, treatment with DPA (250mg/kg intraperitoneally) caused analgesia.
After lesion of ICM, DPA had no effect on analgesia caused by acupuncture point or non-point stimulation, with or without lesion of ISp. Therefore, it was shown that DPA action is equivalent to that of ICM lesion. After excluding DPA action on the ICM by lesion of the ICM, DPA augmented naloxone reversal analgesia. Augmentation was more marked in the presence of R₂than in the absence of R₂. Individual variations in effectiveness of such analgesia disappeared after DPA treatment. It was concluded that 1) DPA inhibited the analgesic inhibitory system and that 2) DPA abolished the individual variations in effectiveness in naloxone reversal analgesia.

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We reported that the central pathway (R₂) of acupuncture point stimulation-produced analgesia (AA) is different anatomically as well as pharmacologically, from (R₁) of the acupuncture non-point stimulation-produced analgesia (NAA) appearing after lesion of the analgesia inhibitory system, the lateral centromedian nucleus (ICM) . For example, R₂and R₁pathways passed through the dorsal periaqueductal central gray (dPAG) and the lateral PAG (IPAG), respectively. Since NAA is produced by lesion of the ICM, the effect of lesion and stimulation of the ICM on dPAG and IPAG stimulation-produced analgesia (dPAG-SPA), and stimulation effect of the ICM on evoked potential in the IPAG caused by acupuncture point or non-point stimulation have been investigated. Pain threshold was measured by rat tail flick latency. For stimulation of the ICM, dPAG and IPAG, 600 msec frain of biphasic 80 Hz waxing wave was applied. This pulse stimulus was applied with ¹/sec frequency. Stimulus strength was limited by a constant current apparatus and 50pA and 200μA maximum for the PAG and ICM stimulations, respectively. ICM lesion had no effect on the dPAG-SPA, while augmenting IPAG-SPA. Stimulation of ICM has no effect on the dPAG-SPCA, while inhibiting IPAG-SPA completely during stimulation. Among 21 cases of IPAG evoked potentials, 13 were completely inhibited by ICM stimulation, while 4 were partially inhibited and 4 others showed no change. No regional change in IPAG histological examination could be fo and between the stimulated region and the recorded region in IPAG in the above experiments. It was concluded that analgesia inhibitory system exerted its inhibitory effect on the IPAG.

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It was reported that hypophysectomy abolished analgesia in acupuncture anesthesia (AA) measured by tail-flick and vocalization tests in rats. However, Fu et al reported that hypophysectomy did not influence AA measured by writhing test using phenylquinone in mouse. In the present experiment, the effect of hypophysectomy on AA measured by writhing test in rats has been investigated. Intraperitoneally applied 2.5 mg/kg phenylquinone caused writhing. Acupuncture stimulation completely abolished writhing behavior in acupuncture effective animals classified by the tail-flick test. After hypophysectomy, acupuncture stimulation did not prevent writhing caused by phenylquinone. The difference between Fu's results and those here might be the difference in analgesia caused by different acupuncture stimulation, since Fu's AA was not blocked by naloxone, while our AA was blocked completely, and Fu's AA was slightly reduced by hypophysectomy, while our AA was completely abolished. It was concluded that hynonhvsectomv completely abolished naloxone reversal AA measured by writhing test.

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The role of the arcuate nucleus of the hypothalamus in acupuncture point stimulationproduced analgesia (AA) and non-point stimulation-produced analgesia (NAA) has been investigated by measuring tail-flick latency of rats as pain threshold. Lesion of the caudal part of the arcuate nucleus abolished both AA and NAA. Stimulation of the caudal arcuate nucleus produced analgesic effect (ARN-SPA) . ARN-SPA exhibited the nature of the desending pain inhibitory system, i. e. ARN-SPA appeared only during stimulation, did not exhibit individual variations in effectiveness, was not blocked by naloxone (1 mg/kg i. p.) and was not influenced by hypophysectomy. ARN-SPA was completely abolished by pimozide (2 m/kg, i. p.) . Dexamethasone (0.4 mg/kg i. p. 24 hr. and 0.2 mg/kg i. p.1 hr before experiment) had no effect on ARN-SPA. ARN-SPA was partially antagonized by lesion of the ventral periaqueductal central gray (v-PAG), in which the dorsal raphe nucleus is located, by methysergide (2 mg/kg i. p.), a serotonin inhibitor or by phentolamine (20 μg intrathecally applied), a catecholaminergic α-blocker. Simultaneously applied methysergide and phentolamine or lesion of the dorsolateral funiculus completely abolished ARN-SPA. Evoked potential in v-PAG was induced by stimulation of the arcuate nucleus. From these results, it was concluded that arcuate nucleus plays a role in the descending pain inhibitory system in AA and NAA. Dopaminergic neurons may be involved in the descending inhibitory system from arcuate nucleus to the ventral PAG and the original region of the catecholaminergic descending system.

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Stress induced analgesia (SIA) producing central pathway was explored by comparing it with that of‘so called’acupuncture analgesia (AA) caused by acupuncture point stimulation and that of acupuncture non-point stimulation produced analgesia (NAA), which appeared after lesion of the analgesia inhibitory system, the lateral centromedian nucleus of thalamus (ICM) . Tail flick latency of Wistar rats was used for measurement of pain threshold. Electric stress shock of 1 sec duration was applied between back and upper thigh at ¹/₅ sec. The stimulus strength was increased from 1.5 mA to 3 mA within 10 min onset of stimulation. Acupuncture point and non-point stimulation were applied to the anterior tibial muscle and the abdominal muscle, respectively, with a stimulus strong enough to cause slight muscle contraction. Lesions of the dorsal and lateral periaqueductal central gray (dPAG and IPAG) and ICM were made by electrode insertion. SIA, caused by electric shock in the present experimental, reached a maximum at 30 min after onset of stimulation and then decreased gradually. Analgesia remained after of stimulation (after effect) . Such SIA was abolished by hypophysectomy, naloxone (1 mg/kg i. p.) or dexamethasone (0.4 mg/kg 24 hr. before, and 0.2 mg/kg 1 hr. before) . Individual variation was observed in SIA, but this variation has no correlation with that of AA. SIA was not influenced by lesion of the dPAG, which is the site of the afferent analgesia-producing pathway in AA from acupuncture point to the hypophysis, or by intrathecally applied naloxone (0.2 μg), which abolished AA. Four days were necessary to recover normal SIA. SIA had no effect on AA for 4 days after after SIA. Like NAA, SIA was abolished by lesion of the 1PAG, however, 1CM lesion, by which NAA was induced by acupuncture non-point stimulation, did not produce SIA in SIA non-effective animals. Analgesia was induced after 1CM lesion by weak stress shock, which did not produce SIA. This analgesia was not antagonized by naloxone. NAA was not influenced by SIA for 4 days. Since 1) SIA was antagonized by either naloxone or dexamethasone, while AA was antagonized only by naxolone and NAA only by dexamethasone, 2) SIA had no effect on AA or NAA for 4 days, were necessary to recover SIA, 3) dPAG lesion or intrathecal naloxone, which abolished AA, had no effect on SIA, therefore, it was concluded that the central analgesia producing pathway for SIA is different from that of AA or NAA.

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Platelet volume was measured in 123 cases with various hematological disorders, using a Coulter Counter, Model ZB-1 with a Channel Analyzer. Normal values of platelet volume in 50 healthy adults were as follows: mode, 6.71±0.83μ³, mean volume, 9.77±0.95μ³, and megathrombocyte index (M. I.), 21.07±2.87μ³In ITP, both platelet volume and the number of megakaryocytes increased. A negative linear relationship was found to exist between volume and numbers. The abnormal peak of particles smaller than 1.6μ³was conspicuous in cases which indicated remarkably low platelet counts, and this peak was regarded as fragments of platelets produced by immunologic aggregation. On the contrary, platelet volume and the number of megakaryocytes decreased in hypoplastic anemia. The platelet volume in acute leukemia was lower than normal, especially in cases of acute promyelocytic leukemia with DIC. These platelet volumes gradually returned to normal after complete remission. In the case of paraproteinemia or megaloblastic anemia, platelet volume was always lower than normal, however decreased platelet aggregation improved after plasma exchange or Vit. B₁₂injection. In the case of malignant lymphoma, PNH and myeloproliferative disorders (MPD), the platelet volume was almost within normal limits. However, there was a negative linear relationship between volume and aggregation in PNH. On the contrary, no relationship was revealed to exist between them in MPD. The present study suggests that larger platelets do not always have greater metabolic potential, but platelet dysfunctions result from not only platelet size but various factors in each hematological disorder.

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Transcutaneous PO₂ (tcPO₂) during Astograph was measured in 44 cases (33 asthmatic, 7 non-asthmatic respiratory disorders and 4 normal subjects) . The tcPO₂significantlycorrelated with the PaO₂ (P<0.001) . The Cmin time on the astograph correlated significantly with the maximum tcPO₂time. After inhalation of a bronchial dilator, tcPO₂recurrence timeto the prior state was significantly delayed to the maximum and the final Rrs times on the A stograph, and the minimum tcPO₂ (p<0.001) time. The correlations of the recurrent tcPO₂period from minimum to the prior levels and age, asthmatic types and other respiratory parameters (%FEV, FEV_1.0%and V50/V25 by Chestac-35F and Rrs by MZR-4000) were not found to be significant. The ratio of ascending Rrs and the ratio of descending tcPO₂were notcorrelatable. The minimum tcPO₂ and the prior tcPO₂were significantly correlated (P<0.05) .These results indicated that a more careful observation was required of the respiratory examiner (for example, with the Astograph), especially in relation to those patients with a prior history of hypoxia.

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Transverse muscle sections from 14 adult humans (10 males and 4 females) were studied for estimations on myofibrous organization of hyoid muscles, the number and the size and density of muscle fibers. The samples were embedded in celloidin and double-stained with hematoxylin and eosin, and the results were compared with those on other human muscles. The following results were obtained: 1) In the area of the transverse section of muscle belly, geniohyoid was the largest (an average of 101.5 sq. mm) . Superior omohyoid, inferior omohyoid and sternohyoid were in the range of the smallest area group, with an average of approximately 20 sq. mm. The range of hyoid muscles belonged to hand and foot muscles. 2) The number of muscle fibers per sq. mm. of geniohyoid and mylohyoid was approximately 800 per sq. mm. on the the average, and the female range for this parameter was larger than that for the male. In addition, other muscles were approximately 600 sq. mm. in size. No sex difference could be established. These muscles were as large as the masseter, in which the ranges were narrow in comparison to hand and foot muscles. 3) The total number of muscle fibers in geniohyoid was 80, 000, which was the largest by far. Mylohyoid, anterior belly of digastric and thyrohyoid were ranked in the second group, and stylohyoid, superior omohyoid and inferior omohyoid fell into the group having the smallest number, 40, 000 on the average. 4) Mean muscle fiber size was approximately 1, 000 μm². Data on this were generally greater in males than in females. The size distribution pattern had a tendency toward a multi-peaked pattern with advanced age. The range of muscle fiber mean size was approximately equal to that of hand muscle, was smaller than foot muscle and larger than masseter. 5) On muscle fiber density, geniohyoid and mylohyoid muscle had a density of about 80%, others were from 60 to 70% on the average. These findings were higher than those for masseter' but lower than those for rectus abdominis'.

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The effect of controlled hypotension using adenosine triphosate (ATP) on the hemodynamics and organ blood flow was studied in 16 dogs and 48 rabbits. Overall hemodynamic changes were measured in anesthetized dogs whose mean blood pressures had been reduced to 50% of the control value with drip infusion of ATP. Also, blood flow changes of heart muscle, liver, kidney, spleen, stomach, small intestine and large intestine were measured in anesthetized rabbits under the same controlled hypotensive conditions using ATP and trimetaphan (TMP) . Accompanying hypotension, ATP caused slowing of heart rate. ATP also caused a decrease in TPR, which was proportionately greater than the decrease in blood pressure. ATP increased cardiac output, with stroke volume increasing markedly. Central venous pressure also increased slightly. PaO₂levels increased while PaCO₂levels decreased slightly. Base excess was reduced, but pH did not decrease significantly because of the reduction in PaCO₂levels. In addition, a-v DO₂was reduced but V0₂did not change significantly. ATP caused increased blood flow in the heart muscle and liver, whereas TMP caused decreased blood flow in the heart muscle, stomach, small intestine and large intestine. Overall, ATP afforded greater stroke volume and increased cardiac output while increasing liver and heart muscle circulation, without significantly affecting blood flow in the kidney, spleen, stomach, small intestine or large intestine. Therefore, hypotensive anesthesia using ATP appears to be safer than using TMP.

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In modelling experimental chronic pancreatitis caused by scorpion venom, we found a decrease in toxicity in rabbits undergoing long-term administration of scorpion venom, apparently due to the production of anti-venom. Thus, the experiment was planned to prove the abovementioned hypothesis, and we obtained the following results: 1) By neutralization of antivenom, its production was apparent in rabbits. 2) Anti-venom inhibits hypersecretion of the rabbit pancreas due to scorpion venom. 3) Pathologically and histologically, abnormalities in pancreatic or salivary gland action due to scorpion venom toxicity were not observed when anti-venom was present. 4) Reduced venom, by the anti-venom, resumed to prior levels by increase in the former. 5) In mice injected with a solftion of increased volumes of venom and anti-venom, the series of tissue reactions that are expected to occur due to scorpion venom were confirmed. These experiments lead to the conclusion that increase in venom totally inhibits the already-produced anti-venom. Furthermore, long-term administration of scorpion venom can maintain the state of hypersecretion of amylase. Therefore, the use of this paradigm to mirror chronic pancreatitis is thought to be justifiable.

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Immobilization stress, using a metallic stress cage, was induced in spontaneously hypertensive rats (SHR) and Wistar rats (WR) for 90min. Blood pressure (BP) and heart rate (HR) were recorded every 15min., and plasma norepinephrine (NE) and epinephrine (E) were measured at O, 15 and 60min. intervals during stressing. The effects of i. p. administration of prazosin (0.1., 0.5mg/kg), propranolol (1, 10mg/kg) and labetalol (1, 10mg/kg) on BP or HR responses to this stress were investigated. 1) Both BP and HR began to increase at 30-45min., and maximum BP and HR responses were reached at 60-75min. 2) The BP response was greater in SHR than in W R, and this maximum BP response occurred earlier in SHR than in WR. 3) Plasma NE and E tended to increase at 15min., but returned to the pre-stress level after 60min. 4) Only prazosin (0.5mg/kg) significantly suppressed BP response. 5) It is sug-gested that: 1) SHR is more sensitive to BP changes, 2) BP, HR or plasma catecholamin es are interchangeable, stress phasedependently and 3) The ai-receptor might play a role in BP re-sponse to this stress.

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By supravital staining of blood from an erythroleukemic, we observed erythrocytes which were golf ball-like in appearance, suggesting abnormal hemoglobin presence. In hemoglobin electrophoresis by starch gel, the abnormal extraband was mobilized faster than the Hb A. Then, we purified this abnormal extra-band by anion-exchange column chromatography, DEAE-Sepharose CL-6B. Purified, this abnormal fraction, which was treated with PCMB (p-chloromercuribenzoic acid), was then electrophorized, and only beta-chain and non-dissociated he-moglobin were detected: alpha-chain was not. These results suggested this abnormal hemoglobin was Hb H.

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[in Japanese]

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