The incidence of M-component in 165 patients with leukemia and 64 cases with malignant lymphoma, and the relationship between M-component and the clinical course were studied by a combination of cellulose acetate electrophoretic and agar immunoelectrophoretic analysis. By cellulose acetate electrophoresis, M-component was detected in 3.0% leukemia and in 6.7% of malignant lymphoma. The M-components were classified into two groups according to the electrophoretic pattern. Pattern I showed a clear dense narrow band. Pattern II was a faint obscure abnormal band often with two or more associated abnormal bands. Pattern I was found in 6 cases. Except for one case with acute lymphocytic leukemia in which the M-component was accompanied by severe liver disease prier to death, M-components of this type were detected in the sample examined initially and correlated well with the course of the malignant disease. Pattern II was found with regression of the tumor in 3 of 4 cases. This type of M-component was suggestive of imbalance in the clonal distribution of immunoglobulin-producing cells as a result of tumor cell infiltration of the immunoglobulin producing system; or of enhancement accompanied by increase of immunoglobulin-producing cells during remission of the tumor. However, in one case of reticulum cell sarcoma, chemotherapeutic factors seems to have contributed to the occurrence of pattern II. By agar immunoelectro-phoresis, changes in the IgM precipitation line suggestive of low amounts of M-component and undetectable by cellulose acetate electrophoresis (“abnormal IgM”) were observed in 11 cases with leukemia and 6 cases with malignant lymphoma. It seems that these M-components belong to the pattern II found with cellulose acetate electrophoresis. In these cases normal parts of the IgM precipitation line were well preserved and two or more abnormalities were frequently found. In leukemia, except for a few cases, this type of M-component appeared transiently during remission of malignant diseases and was associated with severe chronic infectious diseases. In malignant lymphoma, the changes were detected in the first sample without significant complications and lasted for a long time. It seems likely that many factors such as infection, remission of tumor, chemotherapeutic factors and tumor cell infiltration into immunoglobulin producing system are required for the production of the “normal IgM” in leukemia. This is contrary to malignant lymphoma, in which imbalance in the clonal distribution of immunoglobulin-producing cells, detectable as “abnormal IgM”, occurs as a result of tumor cell infiltration of the immunoglobulin-producing system. Clinically, the cases with M-component pattern I had short survivals. The survival of patients with pattern II varied. In many cases, leukemic potients with “abnormal IgM” survived for a long time. In malignant lymphoma, the survivals were not affected by the presence of M-component of this type. In general, the presence of M-component showed the failure of the immunologic response. However, in some cases such as patients with “abnormal IgM” which appeared at remission of leukemia, occurrence of M-component indicated the process of recovery from the immunodeficient state, To discuss the clinical significance of M-components, the patterns of M-components and basic factors, which arise from imbalance in the distribution of immunoglobulin-producing cells, should be considered.
There are a few reports about the effect of splenectomy done after tumor transplantation on tumor growth and cell-mediated immunity. In this study, splenectomy was performed in PDS mice transplanted s. c. with Erlich ascites tumor cells before and after the transplantation to clarify the significance of splenectomy in tumor-bearing bodies. The tumor size and macrophage migration inhibitory activity (MIF) were measured as parameters of cell-mediated immunity with the lapse of days after the transplantation. 1. Effect of splenectomy on tumor growth and the survival period of mice transplanted with 5×106 tumor cells/mouse. (1) In the first group undergoing sham operation 7 days before transplantation, all mice died of tumor within 30-50 days after the transplantation. (2) In the second group undergoing splenectomy 7 days before transplantation, the tumor propagated temporarily then regressed completely in each mouse. (3) In the third group that underwent splenectomy 5 days after transplantation when the tumor had become palpable, the tumor regressed completely in 85% of mice. The rest of the mice died of growing tumor. (4) In the fourth group undergoing operation 10 days after transplantation, all mice died of the rapidly growing tumor and died earlier than the first group. 2. Effect of splenectomy on tumor growth and the survival period of mice transplanted with 5×105 tumor cells/mouse. (1) In the fifth group undergoing sham operation 7 days before transplantation, all mice died of tumor similar to the first group. (2) In the sixth group undergoing splenectomy 10 days after transplantation, 40% of mice died of tumor growth similar to the fifth group. The remaining 44% of mice survived 2 times longer than the fifth group and the tumor regressed completely in 16% of the mice. 3. Effect of splenectomy on the MIF of regional axillary lymph node cells. In every group, the MIF has a close relationship with the tumor growth. The MIF reached its maximum level on about 5 days after transplantation by which time the tumor had become palpable in the first and the fifth group. Thereafter, MIF decreased and had disappeared by 2 weeks after transplantation. In the mice in which the tumor regressed completely, a weak MIF was found during tumor growth and this was still moderate 2 weeks after the complete tumor regression. Splenectomy seems to be useful in the relatively early cancer as it inhibits relapse after the radical operation.
The effect of electrical stimulation of unilateral right and left stellate ganglia (SG) on coronary hemodynamics and the cardiac surface electrocardiogram (ECG) was studied in openchest anesthetized dogs. The results were as follows: 1) Both right and left SG stimulation resulted in significant increase of mean coronary blood flow, stroke diastolic coronary blood flow, left ventricular segmental contraction, heart rate and aortic blood pressure, with decrease of stroke systolic coronary blood flow, and coronary vascular resistance, Except for heart rate and blood pressure, these changes caused by left SG stimulation were significantly greater in the left circumflex coronary artery (LCX) area than in the left anterior descending coronary artery (LAD) area. However, right SG stimulation disclosed no significant difference between the two coronary areas. Left SG stimulation increased the positivity of the T wave of the cardiac surface ECG of the LCX area and the negativity of the LAD area, while right SG stimulation increased the positivity of the T wave in both areas. The QT interval of the cardiac surface ECG was unchanged or slightly shortened, but the QT ratio by Bazzet's formula was increased in both areas by SG stimulation. The data obtained suggest that the functional distribution of right SG and left SG innervation to the ventricles is different, that the LAD area is predominantly innervated by right SG, and the LCX area is innervated equally by right and left SG. 2) Intravenous (I. V.) administration of phentolamine (0.1mg/kg/min.) resulted in no significant change in hemodynamics or ECG patterns produced by SG stimulation, as compared. with untreated animals. However, administration of propranolol (0.5mg/kg I.V.) inhibited the effect of SG stimulation on coronary hemodynamics and cardiac surface ECG. This suggests that the effect of electrical SG stimulation may be caused by catecholamine release at sympathetic nerve endings, hence, beta receptor stimulation at coronary artery areas.
Although carotenoid is one of the typical pigments in Staphylococcus aureus, its properties and physiological role have not been well characterized. This paper examined carotenoid of S. aureus in regard to (1) factors affecting its production. (2) chemical properties and (3) its effect on liposomal permeability. (1) Carotenoid content increased during the late logarithmic growth phase. Production was potently accelerated by the addition of 10% NaCl (10 fold), 2% glycerin (10 fold) and 1% glycerolmonoacetate (250 fold). Oxygen was necessary but visible light did not effect the production. (2) The major component of carotenoid was C30 Diaponeurosporenoic acid methyl ester. Minor components were Diaponeurosporene, Diapo- ∫ -carotene, Diapolycopenoic acid methyl ester, Diaponeurosporene ester and a hydroxyl derivative of Diaponeurosporene. Staphylo-coccal carotenoids were all C30. (3) The addition of carotenoid to liposomes (made of staphylococcal phospholipids) increased the permeability for glycerol and glucose. This indicates that production of carotenoid may be an adaptational response of the bacteria.
A survey of inpatient alcoholics in Okayama Prefecture was carried out on September 1, 1977. Questionnaires for each alcoholic were sent to the psychiatrists of 23 psychiatric hospitals and wards (the total number of psychiatric beds was 4591). Psychiatrists from 21 hospitals (93.9% of the total beds) supplied data. There were 4198 psychiatric inpatients, of whom 230 (5.5%) were alcoholics. Of these alcoholics, 14 were women (6.1% of all alcoholics). Marked differences were found among the hospitals concerning the number of inpatient alcoholics. The number of senile alcoholics over 60 was high (49 persons, 21.4%) and many inpatient alcoholics (102 persons, 44.3%) continued admission for more than one year. The hospital bills of 110 alcoholics (47.8%) were paid by Seikatsuhogo (financial support by the Welfare Office) and obligatory admissions were only 3 (1.3%) of the total alcoholics. 83 of the guardians (36.1%) were spouses and 20 (8.7%) were mayors or village heads. 30.4% of them remained divorced. Thus, inpatient alcoholics had handicaps in family and economical backgrounds, and it is necessary to carry on treatment sufficiently supported by social work.
In order to evaluate the effects of isoproterenol on cerebral circulation and tissue metabolism, hemispheric blood flow (HBF) and the concentration of adenosine 3', 5'-monophosphate (cyclic AMP) in brain tissue were measured in 99 Wistar strain rats under light nitrous oxide anesthesia. Differences in the effects of l- and dl-isomers of isoproterenol were also studied. HBF was measured by the modified 133Xe tissue direct count method previously described by Matsumoto. The advantage of this method was the ability to measure HBF and tissue metabolic valiables simultaneously, even in small animals. Cyclic AMP was measured by radioimmunoassay kits (Yamasa Shoyu Co., LTD). The control values of HBF and cyclic AMP at normocapnia (PaCO2 38.9 mmHg) were 83.3±2.4 ml/100g/min and 1.26±0.05 μmol/mg; at hypocapnia (PaCO2 20.7 mmHg), 62.5±2.2 ml/100g/ min and 1.26±0.07 μmol/mg; and at hypercapnia (PaCO2 63.6 mmHg), 139.6±5.8 ml/100g/ min and 1.33±0.10 μmol/mg respectively. During normocapnia and hypocapnia, continuous intravenous administration of isoproterenol (0.4 μg/kg/min) for 30 minutes caused a significant increase in both HBF and cyclic AMP, while the mean arterial blood pressure (MABP) fell considerably. Both l- and dl-isomers of isoproterenol caused similar increases in HBF ranging from 128% to 140% of control values. The increase in cyclic AMP was between 130% and 144%. The correlation between HBF and cyclic AMP values in individual animals was statistically good at normocapnia. During hypercapnia HBF did not show any changes, while cyclic AMP increased. Administration of l-isoproterenol in different doses (0.2, 0.4, and 1.6 μg/kg/ min) demonstrated a dose-dependent increase in cyclic AMP, but the increase in HBF was not dose-dependent. Continuous administration of HCl solution of the same acidity as isoproterenol hydrochloride (pH 3.5-5.5) increased HBF without associated changes in cyclic AMP. This result suggests that arterial acidosis induced by either isoproterenol or HCl solution is at least partially responsible for the increase in HBF. It was concluded that increase in regional cerebral blood flow during intravenous administration of isoproterenol may be mediated not only via direct vasodilation of cerebral vessels, but also through enhancement of cerebral metabolism, especially stimulation of the adenyl cyclase-cyclic AMP system.
The level of pollutants, especially SOX, are becoming lower in the air. The prevalence rates of respiratory symptoms such as cough and phlegm are also decreasing, but the sampling size must be increased to know the effects of air pollution. Self-completion methods have the merit of increasing the sampling size, but the reliability of self completion method has been argued. In previous studies, agreement between the prevalence rates of self-completion methods and those of personal interview was tested. But this agreement is not considered to be always necessary, if a specific relationship between the two methods is observed in the range of the prevalence rate. From this point of view, the correlation and regression analyses of cough, phlegm, dyspnea and asthma symptoms were made, and the reliability of the self-completion method discussed. The data of 19 districts in Okayama prefecture was used, where surveys using both methods were attempted. The questionnaire for the personal interview method was the BMRC's standard questionnaire, and the questionnaire for self-completion method was made by referring to the CMI's and other self-completion questionnaires. The results were obtained as follows: 1. On regression analyses, the regression coefficients were statistically significant in many cases (p<0.01 for eight cases and p<0.05 for three out of twelve cases). 2. The correlation coefficients between the two methods were large, especially for the analyses of cough and phlegm. For phlegm, the lower limits of 95% confidence interval of correlation coefficients ranged from 0.833 to 0.982. For cough, it ranged from 0.630 to 0.941. 3. From the results of 1 and 2, it was considered that the self-completion method using a simple questionnaire was as useful as the personal interview method to study the prevalence of cough and phlegm in the districts.
The present study has been undertaken to clarify the ascending projections of the inferior colliculus (IC) to the posterior thalamus, particularly the medical geniculate body (MGB), using the Nauta-Gygax and Fink-Heimer methods. The ventrolateral part of the central nucleus of IC projects mainly to the laminated ventral principal part and the lateral portion of the magnocelluar part of MGB. The projections to the laminated ventral principal part are topically organized mediolaterally, i.e., the medial laminae of the central nucleus of IC project to the medial laminae of the ventral principal part of MGB, whereas the more lateral laminae of the central nucleus send fibers to the more lateral laminae of the ventral principal part of MGB. The projections of the central nucleus of IC to the laminated ventral principal part of MGB also appear to be organized anteroposteriorly and dorsoventrally. The dorsomedial part of the central nucleus of IC projects to the ventromedial portion of the ventral principal part, the magnocellular part, and the ventral portion of the dorsal principal part of MGB. The external nucleus of IC is situated lateral to the central nucleus and extends anteriorly to form the anterior extremity of IC. It projects to the magnocellular and ventral principal parts and to the ventral portion of the dorsal principal part of MGB, including the deep dorsal nucleus of Morest (1964). In addition, it sends fibers to the deeper layers of the superior colliculus (stratum griseum intermediale and profundum) and to the anterior pretectal and suprageniculate nuclei. The inferior colliculus projects to the nucleus of the brachium of the inferior colliculus and the interstitial nucleus of the inferior brachium and to the central gray of the midbrain. Each part of IC is connected with other parts by intrinsic fibers. IC sends fibers to the dorsal part of the contralateral inferior colliculus, particularly the dorsomedial part of the central nucleus, through the commissure of the inferior colliculus. Only a few fibers pass by way of the inferior brachium to MGB on the contralateral side.
The activities and properties of two inhibitors of cell proliferation, which are present in the supernatant of rat liver, have been studied in L929 fibloblast systems. 1) One factor, which had arginase activity, completely inhibited cell proliferation by depletion of arginine in the culture medium. 2) The other factor was stable to Trypsin-, RNase- and Heat-treatment, and primarily inhibited protein synthesis. Inhibition of DNA synthesis was thought to be a secondary effect. 3) Whether the second factor changes the biological activity in regenerating liver is now under investigation.
The effects of four stereoisomers of β-hydroxyglutamic acid (BHGA) and related substances were examined on the electrical activity of the PON (periodically oscillating neurone) identified in the subesophageal ganglia of the African giant snail (Achatina fulica Férussac). 1) Erythro-L-(eL-) and threo-L-BHGA showed an inhibitory effect on the electrical activity of the PON, and critical concentrations of these two substances to produce the effect (by the bath application) were 10-63×10-6 and 3×10-510-4 kg/l respectively. Erythro-D- and threo-D-BHGA had no effect at 10-4 kg/l. 2) Of the BHGA related substances examined, erythro-ibotenic acid (I acid), quisqualic acid (Q acid), three stereoisomers of tricholomic acid, α-methyl-DL-glutamic acid and erythro-DL-β-hydroxyaspartic acid showed an inhibitory effect on the PON, and the critical concentrations of these substances were respectively 3×10-610-5, 10-5, 10-4, 10-4, 10-4, 10-4 and 10-4 kg/l. 3) It was confirmed by the microdrop application that eL-BHGA, I acid and Q acid directly hyperpolarized the PON membrane. 4) In the chloride free medium, eL-BHGA, I acid and Q acid showed the same hyperpolarizing effect as in physiological medium by microdrop application. The hyperpolarization caused by these substances was not dependent on chloride ions. 5) The resistance of the PON membrane was not changed by eL-BHGA at 10-5 kg/l as compared with the physiological state. But, under a higher concentration (10-4 kg/l), it decreased. 6) eL-BHGA was considered as the inhibitory transmitter of the PON or as an agonist of an unknown inhibitory transmitters of the PON.
The present study attempts to study the comparative anatomy of the parageniculate nucleus in carnivores. In Felidae it is closely applied to the lateral margins of the posterior lateral and suprageniculate nuclei, and is composed of small, deeply stained and fusiform cells. Caudally it lies just lateral to the ventrolateral part of the lateral pulvinar nucleus and to the suprageniculate nucleus. As the dorsal lateral geniculate nucleus appears, the parageniculate nucleus extends ventrally between the dorsal lateral geniculate nucleus and the suprageniculate nucleus or the inferior pulvinar nucleus. In the other carnivores examined, the parageniculate nucleus tends to be confined to the lateral margins of the lateral pulvinar and suprageniculate nuclei. At the most anterior levels of the dorsal lateral geniculate nucleus, the parageniculate nucleus extends ventrolaterally to reach the region just dorsomedial to the dorsal lateral geniculate nucleus, but does not extend between the geniculate nucleus and the dorsal thalamus proper. The parageniculate nucleus is regarded as a connecting cell group between the dorsal lateral geniculate nucleus and the dorsal thalamus proper, and may be a dorsal thalamic derivative.
Innumerable juvenile polyps were recognised in the stomach of an18-year-old girl. The clinical and pathological observations of the propositus have been already reported (in “Japanese Journal of Gastroenterology” and “Gastroenterology”). Her elder brother underwent a subtotal gastrectomy because of gastric polyposis at 14 years of age. Supplementary data of their clinical findings are given. They had no extragastric polyps on roentgenographic and endoscopic studies. A classification of this hereditary syndrome as a newly designated entity, juvenile polyposis of the stomach was proposed. Both siblings are now in good health.
An electrode was stereotaxically implanted in the mesencephalic ventromedial tegmentum (VMT) [A: 44.5, L: 22.5, H: -5.0-5.5] of each of ten cats. Subsequently two elèctrodes were placed in the rostomedial [A: 1415, L: 45, H: 45] and anteroventral [A: 1719, L: 45, H: 45] parts of the head of the ipsilateral caudate nucleus (CN). Four or five days later the VMT was electrically stimulated in three cats to induce behavioral changes which apparantly resembled human athetoid and choreiform movements. Square pulse current was 2-10 volt, 0.5-1.0 msec in duration and 20-100/sec in frequency. 1) The results of high frequency stimulation of the VMT were as follows. 1 Arrest of all kinds of voluntary movements, and ipsilateral miosis with adduction were observed immediately after the start of stimulation. 2 Turning or circling to the opposite side, elevation or choreo-athetoid movements of contralateral forelimb, and licking or chewing followed two to four seconds later. These movements continued during the electrical stimulation and lasted even after cessation of the stimulation. 3 Vegetative phenomena such as tachycardia or urination were also seen occasionally. 2) Decapitation was performed after irrigation of the brain by 10% formalin. Histological study revealed that the tip of the electrode was stituated in the VMT containing the dorsomedial part of the substantia nigra. 3) High frequency stimulation of the VMT led to numerous firing of neurons of the rostromedial part of the ipsilateral CN, which lasted for several seconds after cessation of the stimulation. Electrical stimulation of the rostromedial part of the CN induced choreoathetoid movements and turning, which were quite similar to those produced by stimulation of the VMT. 4) Additional CN stimulation altered the involuntary movements induced by stimulation of the VMT. Namely, stimulation of the rostromedial part of the CN increased both choreoathetoid movements and turning in cats. On the other hand, stimulation of the anteroventral part of the CN decreased them in cats. 5) Finally, turning and circling induced by the VMT stimulation intensified following parenteral administration of L-Dopa, and diminished with haloperidol. These results suggest that the nigrostriatal dopaminergic system plays an important role in the production of circling and choreo-athetoid movements. Especially, the caudate neurons which fired abnormally following repetitive VMT stimulation might be a trigger of these movements.
An electrode was stereotaxically implanted in the unilateral dentate nucleus (DN), the contralateral ventrolateral nucleus of the thalamus (VL) and on the surface of the contralateral anterior sigmoid gyrus (ASG) in thirty-five cats. The evoked responses from the contralateral VL and ASG following DN stimulation were studied using an averaging computor technique. Electrical stimulation of DN was commenced in an unanesthetised state 4 to 5 days after the implantation. Square pulse current, 0.2 msec in duration was applied at a frequency of 1 Hz. Modification of the evoked responses was studied following parenteral administration of various centrally acting agents. The results were as follows. 1) Single stimulation of the DN demonstrated evoked responses in the contralateral VL with N1 (first negative), P1 (first positive), N2 (second negative), followed by P2 (second positive), and N3 (third negative). Peak latencies of these waves were estimated to be 0.8±0.1 msec in N1, 1.1±0.2 msec in P1, 1.5±0.3 msec in N2, 2.4±0.4 msec in P2, and 5.3±1.2 msec in N3. N1 and N2 corresponded to presynaptic tract response and postsynaptic relayed response respectively. From the latencies of N1 and the distance between VL and DN (21 mm), the conduction velocity in the dentato-thalamic pathway was roughly calculated as 23-30 m/sec. 2) The evoked responses on the contralateral ASG following a single stimulation of the DN demonstrated a wave form composed of P1, N1, P2, and N2. Peak latencies of these waves were estimated to be 2.1±0.4 msec in P1, 3.3±0.5 msec in N1, 5.8±0.7 msec in P2, 13.2±1.9 msec in N2. P2 and N2 is corresponding to Creutzfeldt's primary EPSP and secondary EPSP respectively. 3) The effects of various centrally acting agents on the above mentioned evoked responses were observed (See table 3). 1 L-5HTP markedly decreased the amplitudes of both P2 and N2 of ASG responses. PCPA caused no paticular changes. 2 AOAA also caused effects upon ASG responses similar to L-5HTP. A subconvulsive dose of picrotoxin caused no particular changes. 3 Atropine decreased the amplitudes of both P2 and N2 in ASG. Physostigmine caused no particular changes. 4 L-Dopa and ET495 tended to stabilize ASG responses especially when it was in the suppressed state. Reserpine and haloperidol caused no particular changes. These data suggest that 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), acetylcholine (ACh), and dopamine (DA) do not play a primary role in the dentato-thalamocortical pathway but work indirectly through other neuronal pathways. This method using evoked responses seems to be useful to know the site and the time course of drug action in relation to the function of a pathway.
A specific dog C-peptide radioimmunoassay system was established with a single antibody method using synthetic dog C-peptide as standard. The measurable range was between 0.4 pM/ml and 25.6 pM/ml. The coefficients of variation of Within- and Between-assay were 6.0 and 10.8%, respectively. Dog C-peptide immunoreactivity (CPR) and immunoreactive insulin (IRI) level in the superior pancreaticoduodenal (pancreatic) vein were measured in fasting and after loading of glucose or arginine into the superior pancreaticoduodenal (pancreatic) artery. Fasting dog CPR level was 2.73±0.46 pM/ml in the pancreatic vein and was 0.67±0.03 pM/ml in peripheral vein. The molar ratio of CPR/IRI was 1.42 in the pancreatic vein and 6.09 in peripheral vein. Glucose (10 mg/kg/min) infusion into the pancreatic artery evoked a prompt and parallel maximal increase in CPR and IRI within 3 min. The CPR concentration increased from 3.1 pM/ml to 6.5 pM/ml and the IRI concentration increased from 1.7 pM/ml to 4.6 pM/ml at the peak. Arginine (250 mg/kg/min) infusion resulted in a prompt, parallel increase in CPR and IRI. The CPR concentration increased from 3.2 pM/ml to 5.8 pM/ml, and the IRI concentration from 1.7 pM/ml to 4.4 pM/ml at 40 sec, respectively. The insulin-to-C-peptide ratio showed approximately equimolarity.
Immunoreactive dog C-peptide [CPR] and insulin [IRI] concentration in the superior pancreaticoduodenal (pancreatic) vein of normal dogs were measured after administration of neurotensin, xenopsin, γ-hydroxybutyric acid [GHB], 2-Br-α-ergocryptine [CB154], pimozide, and substance-P into the superior pancreaticoduodenal (pancreatic) artery. The effect of neurotensin on B cell secretion was studied in hypophysectomized (10th to 14th day post-hypophysectomy) dogs. In normal dogs, the administration of synthetic neurotensin (10 μg/kg) induced a mild hyperglycemic response with parallel and biphasic increases in both CPR and IRI levels. In hypophysectomized dogs, basal levels of pancreatic CPR and IRI were reduced to about 14% and 55% of the control, respectively. Neurotensin had little effect on pancreatic B cell secretion. Administration of synthetic xenopsin (10 μg/kg) caused mild hyperglycemia and rapid equimolar increases of CPR and IRI in the pancreatic vein. GHB had suppressive effects on both CPR and IRI secretion. Administration of a high dose (500 mg/kg) of GHB showed a more marked decrease in CPR and IRI than that of the low dose (100 mg/kg). The degree of suppression in CPR and IRI secretion was nearly equimolar. A bolus injection of CB154 (200 mg/kg) had caused mild hyperglycemia and biphasic CPR and IRI increases, but after premedication with pimozide (1 mg/kg, i.m.) the same dose of CB154 administration resulted in decrease of CPR and IRI concentrations in the pancreatic vein. With infusion of synthetic substance-P (50 ng/kg/min) for 30 min, CPR and IRI concent-rations in the pancreatic vein were reduced parallel and were nearly equimolar. The above findings indicated that C-peptide and insulin were released from the B cell in equimolar concentrations after stimulation by various CNS affecting agents.
Feedback regulation of insulin secretion from dog pancreatic B cells by exogenous insulin was demonstrated. Dog C-peptide immunoreactivity (CPR) concentration in the superior pancreaticoduodenal (pancreatic) vein was measured as an index of endogenous insulin secretion from B cells. Exogenous monocomponent (MC) insulin was administered into superior pancreaticoduodenal (pancreatic) artery of normal dogs which had various concentrations of blood glucose. When the blood glucose level was maintained at about 400 mg/dl, bolus injection of MC insulin (0.1 u/kg) into the pancreatic artery caused about 8.3% suppression of CPR level in the pancreatic vein. However, when the blood glucose concentration was approximately 180 mg/dl, suppression of the CPR level in the pancreatic vein was about 41%. With a fasting blood glucose concentration, exogenous MC insulin caused about 35% suppression of CPR level, but exogenous dog C-peptide (0.2 pM/kg/min) infusion did not affect the IRI concentration in the pancreatic vein.
The pharmacokinetics of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) were analysed by measuring its disappearance rate (K) from the circulating blood using a high-pressure liquid chromatographic technique. An increase in the disappearance rate of FT was observed by treatment with reduced glutathione (GSH)- or tocopheryl nicotinate-treated rats. The clearance rates of FT from the circulating blood in carbon tetrachloride (CCl4)-injured rats were much smaller than those in untreated rats. The unresponsiveness of K values to treatment with GSH or tocopheryl nicotinate was seen in liver-injured rats.