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1. Veratrine greatly sensitizes the action of potassium ions on frog's rectus muscle. Quinine inhibits the sensitizing action of veratrine. 2. Perfusate of the preparation from the stimulated veratrinized hind limbs evokes a contraction of the veratrinized test muscle. 3. The other purfusates of the preparations perfused with Ringer's solution or with veratrine-Ringer's solution do not affect the test muscle. But a similar contraction is observable if potassium chloride of a certain strength, is added to the perfusates. 4. It can be shown that the chemical agent causing the muscular contraction is potassium ions, 5. The above experimental results may be wholly explained by the assumption that veratrine increases the permeability of muscle cell membrane to potassium ions.

Im hinblick auf diese experimentellen Resultate zeitigten alle Immunisierungsmethoden durch die Trachea positive Ergebnisse, ohne Rucksicht auf die Antigenarten und die Einfuhrungsmethode (Rinderserum, -pulver, intratracheale Einspritzung, Einblasen oder Inhalation u. a.). Die Resorptionszustande waren folgende : wenn man mit wasserloslichem Material, d.h. mit Serum, experimentierte, so konnte man infolge der guten Resorption schon nach 30 Minuten Antigen im Blut nachweisen ; wenn man mit nicht-wasserloslichem Material, d.h. mit Rinderserumpulver, experimentierte, so konnte man Antigen im Blut erst nach I Stunde spurenweise und nach 2 Stunden klar und sicher nachweisen, weil das Material durch die Sekretionsfluissigkeit gelost und resorbiert wird. Ich stellte fest, daβ das Stadium, in welchem resorbiertes Antigen im Blut am zahlreichsten erschien, 5 Stunden bis 8 Tage nach der Immunisierung auftrat. Bei mit Rinderserum immunisierten Kaninchen erreichte man die groβte Antigenmenge im Blut bei ca. 0.128-0.512cc. Bei mit Serumpluver imumsierten Kaninchen erreichte die Resorptionsmenge des Antigens im Blut beinahe einen 1 : 20 gegenuber dem Resultate mit Serum (Serumpulver ca. 0.064-0.256 g). Wenn man diese Resultate mit denen von Endo vergleicht, so ergibt sich eine leichte Verschiebung. Er gab an, daβ er bei dem die Antigenitat vergleichenden Versuch mit Trocken- und Feuchtantigen gegen Tracheaimmunisierung mit Feuchtantigen ein zwanzigfach so gutes Resorptionsantigen im Blut nachweisen konnte als mit Trockenantigen. Ich konnte das durch die Trachea im Blut resorbierte Antigen in einem Fall lange Zeit nach der Antikorperbildung, und in einem anderen Fall kurze Zeit danach schwer nachweisen, im letzten Falle namlich wurde die Reaktion undeutlich und verschwand. Die Erscheinung stimmt mit den Angaben von Hamburger u. Moro, Dehne u. Hamburger, Opie u. a. uberein, daβ bei subkutaner Injektion von Antigen die Antikorperbildung spater eintritt und die Retentionszeit des Antigens langer ist.

1. Die Menge der Galle und der Gallensaure der Gallenblasenfistel tragenden Hunde wird durch Bestrahlung des Korpers mit ultravioletten Strahlen vermehrt. 2. Die Menge der Galle und der Gallensaure des Fistelhundes wird durch Futterung mit Ergosterin vermehrt und diese Vermehrungbei Zufuhr von Ergosterin durch Bestrahlung des Hundekorpers mit ultravioletten Strahlen verstarkt. 3. Die Gallensekretion und Gallensaureausscheidung des Fistelhundes wird durch Ftitterung mit Shiitake vermehrt und diese Vermehrung durch Bestrahlung des Hundekorpers verstarkt. Bei Verabreichung von mit ultravioletten Strahlen bestrahltem Shiitake tritt diese viel starker auf als bei Verabreichung von nichtbestrahltem. Aus diesen Ergebnissen scheint hervorzugehen, daβ die Gallensaurebildung im Organismus mit der Bestrahlung des Korpers und der Nahrung eng verknupft ist.

Durch die vorliegenden Versuche wurden einige Eigenschaften der 12-Keto-3-cholensaure, die unter gleichzeitiger Hydratisierung und Reduktion im Kaninchenorganismus in Desoxycholsaure verwandelt im Harn ausgeschieden wird, vergleichend mit denen der anderen Gallensauren untersucht und folgende Daten festgestellt : 1. Die bamolytische Wirkung der 12-Keto-3-cholensaure wurde viel starker als die der Desoxycholsaure gefunden. 2. Die die Pankreaslipase fordernde Wirkung der 12-Ket0-3-cholensaure ist fast gleich der der Cholsaure. 3. Die choleretische Wirkung der 12-Ket0-3-cholensaure ubertrifft weitaus die der Cholsaure. 4. Der Adrenalingehalt der Nebenniere wurde durch parenterale Zufuhr von 12-Keto-3-cholensaure herabgesetzt gefunden, wobei sich die Herabsetzung durch 12-Keto-3-cholensaure etwas starker zeigte als die durch Cholsaure.

The release of indomethacin from fatty-base suppositories, which had been stored at a low (4 degrees C) and a high (25-30 degrees C) temperature for about one month, was examined in vitro and in vivo. In the in vivo experiments, the plasma indomethacin levels after administration of suppositories stored at different temperatures were measured in conscious and anesthetized rats. In the in vitro release test using a dialysis cell method, much lower amounts of indomethacin were released from the suppositories stored at a high temperature than from those stored at a low temperature. The melting point of suppositories stored at a high temperature was higher by approximately 2 degrees C than those stored at a low temperature. In conscious rats, the plasma indomethacin levels attained after the intrarectal administration of suppositories stored at a high temperature were slightly lower than those after the animals were given suppositories stored at a low temperature, but the difference was significant only 30 min after administration. In anesthetized rats, the plasma indomethacin levels were markedly lower than those in conscious rats, and the influence of the storage temperature on the plasma indomethacin levels was clearly observed. These results suggest that in conscious rats many factors such as a locomotor hyperactivity and enhancement of gastrointestinal motility caused by the rectal administration mask the real character of suppositories. The in vitro and in vivo results show that the release of indomethacin from fatty-base suppositories stored at a high temperature is less than the release from those stored at a low temperature.

A patient with a diffuse, small cleaved cell, non-Hodgkin's lymphoma associated with marked hypecalcemia was described. Antibody to the adult T-cell leukemia-lymphoma virus was absent. Although bone marrow was infiltrated by lymphoma cells, destructive or lytic bone lesions could not be detected. The serum level of immunoreactive parathyroid hormone C-terminal (PTH-C) was normal. The serum level of 1, 25-dihydroxyvitamin D was lower than normal. This case suggests that other humoral substances produced by lymphoma cells may be responsible for hypercalcemia.</P>

We constructed a plasmid, pBH103-ME5, in which the region encoding the 10 preS2 amino acid residues and the S domain of the hepatitis B surface antigen (HBsAg) were regulated by the promoter of the yeast repressible acid phosphatase gene. Saccharomyces cerevisiae carrying pBH103-ME5 produced the HBs antigen (yHBsAg), when it was cultured in a medium containing a low concentration of phosphate. The antigen was purified to homogeneity. Its molecular weight was determined by Western blotting to be 24,000, and its amino acid composition agreed well with that deduced from the nucleotide sequence. The C-terminal amino acid sequence of yHBsAg was exactly the same as that predicted from the nucleotide sequence, while the N-terminal amino acid acetylserine, which was followed by 8 amino acid residues coded by the preS2 region. These results indicate that the recombinant yeast produced a single polypeptide consisting of the preS2 region and the subsequent S domain after being processed at the N-terminus

Pulmonary function tests were performed on 252 healthy young subjects free from respiratory and allergic symptoms, and 80 young subjects with past history of nasal allergy (PNA) and 10 subjects with past history of bronchial asthma (PBA). All the subjects were non-smokers. Maximal expiratory flow-volume (MEFV) curves were visually classified into five types (A-E). The percent distribution of type A in healthy subjects was significantly higher than in the PNA group, while the total sum of percentage of types B, C, and D in the PNA group was significantly higher than in the healthy subjects. The percent distribution of type E in the PNA group was similar to that in the healthy subjects. The percent distribution of MEFV types were significantly different between healthy males and healthy females. The percent distribution of types A, B and E were the highest in healthy subjects, PNA and PBA groups, respectively. Conclusively, the difference in the percent distributions of MEFV types was recognized among healthy subjects, PNA and PBA groups.

Antroduodenal contractions were studied in rat preparations. Augmented duodenal contractions occurred spontaneously in coordination with antral contractions in normal and saline-pretreated preparations. The coordination did not occur when muscle layers and the myenteric plexus were transversely cut at the duodenum just anal to the gastroduodenal junction. In silent preparations, the coordinated contractions were produced by neostigmine or domperidone. When the antroduodenal junctional zone was pretreated with benzalkonium chloride, the augmented duodenal contractions did not occur spontaneously, and even after administration of neostigmine and domperidone although antral contractions occurred spontaneously. In these preparations, there were notably few myenteric neurons in the junctional zone, but the neurons were distributed normally in the areas where motility was recorded. The results suggest that myenteric neurons mediate antroduodenal coordinated contractions and that the coordination is modified by myenteric cholinergic excitatory and dopaminergic inhibitory pathways.

Post-traumatic colonic stenosis (obstruction) is rare. We experienced a case of sigmoid obstruction due to blunt abdominal trauma. A 75-year-old man was hit on the lower abdomen 3 days before admission and gradually developed abdominal pain and distension. Laboratory data showed severe inflammation and a barium enema disclosed obstruction of the sigmoid colon. Conservative treatment was carefully carried out, because there was no sign of peritoneal irritation and there were passages of normal stool and flatus. The sigmoid obstruction gradually improved and the stenosis was almost undetectable on a barium enema on the 51st hospital day. An abdominal contusion is the most likely causal factor in this case. Compression of the sigmoid colon between the abdominal wall and the promontory of the pelvis is the most possible explanation.</P>

The hepatitis B virus surface antigen containing the preS2 nine amino acid sequence produced by a recombinant Saccharomyces cerevisiae (yHBsAg) was purified and its physicochemical properties were determined. Ultrastructurally, the yHBsAg was found to be a homogeneous spherical particle with a diameter of 24 +/- 4 nm. The homogeneity of the yHBsAg particles was also demonstrated by analyses of their buoyant density and isoelectric point. They consisted of protein (53%), lipid (36%) and carbohydrate (11%), and the alpha-helix content was estimated to be 32%, differing from the reported values for human plasma-derived HBsAg (hHBsAg). Immunodiffusion analysis showed that the antigenic specificity of yHBsAg was identical to that of hHBsAg. Immunization of mice demonstrated that the immunogenicity of the yHBsAg was significantly higher than that of hHBsAg.

<p>We present a case of pre-elastofibroma-like lesion, a kind of elastic-producing fibrous tumor. The small colonic polyp, which was found in a 49-year-old asymptomatic man in association with a large colonic adenoma, showed submucosal nodular deposits of fine granular or fibrillar eosinophilic materials with interspersed fibroblastic cells. Elastic stain revealed these deposits to consist mainly of dark gray granular or partially fibrillar dense elastinophilic materials, most of which were digested with elastase. This stromal lesion somewhat resembled a pre-elastofibroma. Therefore, pre-elastofibroma-like lesions should be kept in mind as a possible origin of colonic polyp.</p>

In order to elucidate the mechanism of latent infection of herpes simplex virus (HSV), reactivatable latency of three avirulent strains (SKO-1B, -GCr Miyama, SKa) of HSV type 1 was comparatively examined in a mouse latency model. The SKO-1B strain showed high rate of virus reactivation from explanted trigeminal ganglia without n-butyrate enhancement, while the other two strains showed a very low rate of virus reactivation in the absence of n-butyrate. In the presence of n-butyrate, however, the rate of the -GCr Miyama strain jumped to a comparable level with that of SKO-1B, although the rate of SKa remained at a low level. A more precise follow-up experiment changing the virus dose highlighted the difference of the ability to reactivate from the latent state between SKO-1B and -GCr Miyama. Virus titer in trigeminal ganglia during acute phase, infectivity to cell lines of neural origin, and susceptibility to acyclovir and phosphonoacetate were assayed to know the reasons for the variation in the ability of reactivatable latency among these strains. It was concluded that the reduced infectivity to neural cells, and limited ability of reactivatable latency shown by the SKa strain could mainly be attributed to the deficiency of thymidine kinase activity.</P>

The association between the extent of left ventricular (LV) hypertrophy and severity of ventricular or atrial arrhythmias are examined. Two-dimensional echocardiography and 24-h Holter electrocardiography monitoring were performed in 60 patients with hypertrophic cardiomyopathy (HCM). According to the distribution of the LV hypertrophy, the patients were divided into three groups: 1. Apical hypertrophy (APH), 2. Septal hypertrophy, and 3. Extensive hypertrophy. Ventricular arrhythmias were found in 82% of the patients and supraventricular arrhythmias were detected in 70% of the patients. Lown grade III and IV arrhythmias occurred significantly more frequently in patients with extensive than with septal hypertrophy. Lown grade III to IV arrhythmias did not occur in patients with APH. Present results show a significant association between the extent of LV hypertrophy and the severity of ventricular arrhythmias in HCM. </P>

The cardioprotective effect of calmodulin antagonists, trifluoperazine (TFP) and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) was examined on the isolated rat heart exposed to hypothermic and ischemic conditions by measuring distribution of lysosomal enzymes in myocardial cells, and leakage of creatine kinase (CK) during reperfusion and postischemic recovery in myocardial systolic function. Experimental hearts were infused with 20 degrees C Krebs-Henseleit bicarbonate buffer (KHB) or KHB containing TFP or W-7 for 2min every 30min during hypothermic ischemia. After ischemia for 120min at 20 degrees C, rat hearts were reperfused at 37 degrees C for 30min. TFP and W-7 improved functional recovery and prevented CK release. In TFP treated hearts, leakage of lysosomal enzymes was reduced significantly, whereas stabilization of lysosomes by W-7 did not occur. These results suggest that calcium-calmodulin dependent enzymes may play an important role in the development of cellular damage of the myocardium during hypothermic ischemia, although levels of leakage of lysosomal enzymes may be unreliable predictors of functional recovery after hypothermic ischemia.</P>

The role of alpha-1 adrenergic mechanism in the shaking stress-induced adrenocorticotropic hormone (ACTH), and plasma noradrenaline secretion and pressor response were investigated using conscious rats. We also studied whether or not central corticotropin releasing hormone (CRH) is involved in the shaking stress-induced ACTH secretion. The shaking stress caused significant elevations of plasma ACTH, noradrenaline, and systolic blood pressure. Intra-third ventricular administration of alpha-1 adrenergic blocker, bunazosin, inhibited the shaking stress-induced ACTH secretion, but did not alter stress-induced noradrenaline secretion and pressor response. Furthermore, intra-third ventricular administration of CRH antagonist, alpha-helical CRH, significantly attenuated stress-induced ACTH secretion. These results indicate that alpha-1 adrenergic pathway and CRH at least partly mediate the shaking stress-induced ACTH secretion.</P>

<P>The tissue concentration of doxorubicin (adriamycin; ADM) and its major metabolite (aglycone I) was examined in mice pretreated with alpha-tocopherol (VE) or coenzyme Q10 (CoQ). In VE-pretreated group, the concentrations of aglycone I of the liver (1, 3 and 5 h after the administration), kidney (1 and 3h) and heart (3h) were significantly higher than those in the saline group. The clinical application of VE or CoQ concomitant with anti-tumor drugs especially ADM, requires caution.

In order to clarify difference of the mucosal immunity in various sites of normal large and small intestines, we studied the population of lymphocyte subsets and immunoglobulin (Ig)-containing cells in situ in biopsy specimens taken from various sites (ascending colon, sigmoid colon and rectum) of the large intestine and from the duodenum using an immunohistochemical method. Monoclonal antibodies against pan-T (Leu 1), cytotoxic/suppressor T (Leu2a), helper/inducer T (Leu3a), suppressor T (Leu15) and natural killer/K (Leu7) cells, and polyclonal antibodies to human IgG, IgA and IgM were used. In the duodenum, intraepithelial lymphocytes (IELs) were more prominent than in the large intestine. Immunoelectron microscopic observation revealed that some Leu2a+ IELs possessed pseudopods extending into intestinal epithelial cells, indicating that some IELs belong to the cytotoxic T cell subset. Leu7+ IELs were scarcely observed and Leu7+/Leu1+ ratio was higher in the large intestine than in the duodenum. Furthermore, the number of Leu7+ cells were more in the distal than the proximal colon. In the lamina propria Ig-containing cells tended to be fewer in the rectum than in the duodenum and the proximal colon. Our findings may suggest the variation of local immune responses and the difference of assigned immunological functions among the various sites of the intestines.

We investigated the antitumor activities of 5-fluorouracil (5-FU), 5'-deoxy-5-fluorouridine (5'-DFUR), 1-hexylcarbamoyl-5-fluorouracil (HCFU) and 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT-207) in combination with hyperthermia in vitro. The antitumor effect of 5-FU (10(-4) M) was slightly enhanced by combination with hyperthermia (42 degrees C) for 2h, and the effect was determined to be additive. Synergistic enhancement of antitumor activity was obtained by the concurrent use of hyperthermia (42 degrees C, 2h) and 5'-DFUR (10(-4) M) or HCFU (10(-5) M). However, the antitumor effect of FT-207 (10(-4) M) in combination with hyperthermia was comparable that of hyperthermia alone. The synergistic enhancement of antitumor activity was not obtained for all drugs when the cells were preheated at 42 degrees C for 2h. On the other hand, when cells were pretreated with drugs before heat exposure, weak interactions were obtained after 5-FU and 5'-DFUR treatment, and a synergistic interaction was obtained after HCFU treatment. It is speculated that the metabolites of 5'-DFUR and HCFU enhance the cytotoxicity of 5-FU, or might change the threshold concentration for a cytotoxic effect of 5-FU in cancer cells.

Twenty-seven previously untreated patients with unresectable non-small cell lung cancer were treated with a 3-drug combination of ifosfamide, cisplatin, and vindesine as a phase II study. Patients received ifosfamide, 1.3g/m2, on days 1 to 5; cisplatin, 20mg/m2, on days 1 to 5; and vindesine, 3mg/m2, on days 1 and 8; with a sufficient parenteral hydration. Courses were repeated every 4 weeks. Twenty males and seven females with a median age of 61 years were treated and fully evaluated. Five patients had stage IIIA, seven had stage IIIB, and 15 had stage IV disease. One patient with adenocarcinoma achieved a complete response and 16 achieved a partial response, for an overall response rate of 63% (95% confidence limit: 45% to 81%). The median duration of response was 34 weeks (range: 9 to 52 weeks). The median survival time was 58 weeks for patients with IIIA/B disease, and 33 weeks for those with IV disease. The major toxicity was myelosuppression, however, it was generally well-tolerated. These results indicate that the 3-drug combination is active against non-small cell lung cancer and warrants further clinical trials.