Direct perfusion of the sinus node artery under a constant pressure of 100mm Hg was arranged in the canine heart in vivo. The administration of dopamine, norepinephrine or epinephrine from 1 to 10μg into the sinus node artery often induced a deceleration of the sinus rhythm, but isoproterenol never caused such a paradoxical response. The higher the dose given, the more frequently was this paradoxical response observed. The participation of a cholinergic mechanism in this paradoxical response was proved by blocking it with atropine and by enhancing it with physostigmine. Furthermore such paradoxical responses were blocked by treatment with hemicholinium, hexamethonium or phenoxybenzamine, none of which blocked the muscarinic action of acetylcholine. The blocking effect of phenoxybenzamine was persistent and selective. The authors assume that naturally occurring catecholamines stimulate the cholinergic neuron at the presynaptic site through the α-receptors and thus, they are cholinergic in effect, causing the paradoxical response of the sinoatrial node.
Effects of adenosine phosphates on lipid synthesis were studied in singular aortic cell culture system, in which a linear relation was shown between the 14C-acetate incorporation and incubation time over 6 hours. Adenosine triphosphate promoted 14C-acetate incorporation into cultured chick aortic intimal cells. The incorporation rate was greater in neutral fat and sterol fraction than in phospholipid fraction. Adenosine mono- and diphosphates as well as adenosine triphosphate accelerated lipid synthesis to the same extent in the aortic cell culture environment.
1) Electric stimuli were given to the ulnar nerve at the elbow in men and the responses (M-waves) were picked up by bipolar surface electrodes placed above the M. abductor digiti V. 2) The kinetic component of the M-wave has a lower threshold than the tonic component in the strength- duration curve. 3) With paired stimulation, both the kinetic and tonic components were noticed on the second response even at a stimulus interval of 2 msec. 4) Similar responses were obtained successively by the repetitive stimulation of less than 20 per sec. At the rate of 30 per sec, the tonic activity was abolished in the fourth or fifth and in the subsequent responses. 5) A test stimulus was applied 10 msec after 10 conditioning shocks. When the rate of conditioning stimulus was more than 10 per sec, the tonic component was abolished and the ‘pure’ kinetic responses were obtained. Full recovery of the tonic component requires 200 and 300 msec after 10 impulses at the rate of 10 and 50 per sec, respectively. The inhibition of kinetic component was observed after conditioning at 200 per sec and the full recovery occurred within 100 msec. 6) It is suggested that during repetitive stimulation the transmitter available for immediate release is exhausted faster in the tonic motor nerve terminals than in the kinetic nerve terminals, probably due to a slower mobilization or larger quantal liberations of transmitter.
Some clinical and immunochemical findings are presented in 203 patients with M-components. These include 148 patients belonging to primary-malignant group - myeloma, primary macroglobulinemia, and potentially malignant type-, 9 patients with malignant lymphomas and various types of M-components, and 46 patients with benign monoclonal gammopathy. When M-component was present, the following findings seemed to support the diagnosis of myeloma: (1) the concentration of IgG-M-components over 2.0g/100ml or that of IgA-M-components over 1.0g/100ml, (2) presence of Bence-Jones proteins in serum or urine, (3) BBC below 3million/mm3, (4) serum albumin below 3.0g/100ml, (5) plasma cells over 10% in the bone marrow, and (6) presence of plasma cells with marked cytological abnormalities. Since there was a considerable overlap between myeloma and benign monoclonal gammopathy, these findings should be evaluated as a whole, not separately, together with other clinical features, and radiological and histological findings. There was no overlap in the concentration of monoclonal IgM between primary and secondary macroglobulinemia, but the number of cases is too small to draw definitive conclusions. The term `potentially malignant type' has been proposed by the author in order to contribute to the study on the pathogenesis of myeloma or related disorders and the development of tumors in general. Since this condition cannot be regarded as wholly benign, patients should be examined repeatedly for a long period. The mechanisms of occurrence of M-components in malignant lymphomas, its relationship to prognosis, and electrophoretic mobility and immunologic types of M-components are discussed.
Quantitative measurements of immunoglobulins were made in sera from 203 patients with monoclonal gammopathies. In IgG myeloma the serum IgG concentration averaged six times the normal level, in IgA myeloma 15 times, and in IgD myeloma 370 times the normal values of respective proteins. In primary macroglobulinemia the average serum level of IgM was 38 times higher than normal. The serum levels of the normal immunoglobulin classes were markedly decreased in these diseases, including Bence-Jones myeloma and biclonal myeloma. Various mechanisms were proposed to account for the reduction of normal immunoglobulins. On the other hand, in benign monoclonal gammopathy there was usually no reduction of normal immunoglobulins. However, in patients with cancer and IgG-or IgA-M-components IgM levels were decreased. The reason for lowered IgM value remains obscure. It was of special interest that one of the patients with a potentially malignant type appeared to be developing myeloma. A marked reduction of the normal immunoglobulin classes seems to be a poor prognostic sign in patients with M-components in the absence of myeloma. Since patients with lymphoma have a marked tendency to hypogammaglobulinemia and closely resemble a primary-malignant group, immunoglobulin changes in patients with lymphomas and M-components are more complicated. A classification of monoclonal gammopathies was proposed on the basis of their pathogenesis after the consideration of our data as well as those from the literature. The concept of the pathogenesis of monoclonal gammopathies presented herein is based on the view that lymphomas, immunologic deficiency diseases, and autoimmune diseases form a ‘trinity’ pathogenetically and etiologically.
In normal postnatal development, physiological regression of the muscular coat is accomplished to the major part in the first 6 months. Thereafter, the medial thickness still continues slowly to diminish and practically attains the level of normal adults in 4 years. With the present histometrical method, the medial thickness at an arterial radius of 100 μ was estimated at 9.8 μ immediately after birth, was reduced to 6.8 μ in 6 months, to 6.5 μ in a year and to 5.9 μ in 4 years, while the value for normal adults was 5.4 μ. In patients with ventricular septal defect (VSD), physiological medial regression does not take place, and the muscular coat retains or increases its neonatal thickness. The medial thickness is correlated with pulmonary blood pressure level and can be expressed by an exponential function of blood pressure. Pulmonary hypertension in VSD is correlated with the dimension of septal defect. Medial hypertorphy in VSD is probably associated with increased vascular resistance of pulmonary circulation.
The activities of the 9 Cl (Nucl. centralis lateralis), 9 LP (Nucl. lateralis posterior) and 43 Pul (pulvinar) neurons were studied in a monkey (Macaca mulatta) using various natural stimuli. The numbers of single neurons responsive to nociceptive stimuli were 4 in Cl; 2 in LP; and 4 in Pul. The receptive fields of some neurons were limited or were represented by the whole body.
Phenoxybenzamine, α-adrenoreceptor blocking agent, produced the potentiation of the relaxing response of taenia coli to transmural stimulation. This potentiation effect was prevented in the presence of atropine. Moreover, the relaxing response caused by nicotine was abolished by phenoxybenzamine. These results imply that phenoxybenzamine has blocking actions on the muscarinic receptor and possibly on the nicotinic receptor, as well as the adrenergic α-receptor.