Responses of the dog saphenous vascular bed to a variety of vasoactive substances were studied under constant flow perfusion. Adrenergic compounds, except isoproterenol, induced a constriction. Releasers of norepinephrine from the sympathetic nerve endings, such as DMPP, tolazoline, TEA and guanethidine also constricted the saphenous vascular bed, and catecholamine-uptake blocking agents such as cocaine and desipramine behaved in the same way. Phentolamine, one of the adrenergic blocking agents, and bretylium, a typical antireleaser of norepinephrine, caused a dilatation. Cholinergic compounds produced a dilatation. Serotonin, angiotensin and vasopressin produced a constriction, while histamine, bradykinin, kallikrein and eledoisin produced a dilatation. Relaxants of the vascular smooth muscle, nitroglycerin, papaverine, dipyridamole and xanthine derivatives dilated the saphenous vascular bed. Ergot alkaloids caused a constriction. Morphine markedly dilated the saphenous vascular bed and nicotinic acid had no activity at all.
The collateral circulation of the limbs was investigated by injection of radioiodinated macroaggregated serum albumin (131I-MAA) into the brachial and femoral arteries of 31 patients with occlusive vascular diseases. The method was found useful as a subsidiary means in evaluating the peripheral circulation in these diseases. In 80% of cases of sympathectomy, arteriovenous shunts were increased by 25% of the control. Higher leakage of 131I-MAA of approximately 90% over the control was observed in a congenital arteriovenous fistula of the leg, which was confirmed by scintiscanning. Linear scanning along the body axis displayed accumulation of 131I-MAA in the lung of control and patients with vascular diseases, suggesting that 131I-MAA had passed through the arteriovenous shunts. Abnormally high radioactivity was observed occasionally at the toes and finger tips with chronic ulcers.
Seven and nine cases of organic and mental impotence, respectively, were examined for changes in circulating blood in the penis after the administration of 131I-human serum albumin. As a result, there was a remarkable difference in the amount of circulating blood in the penis between the two groups. This method of examination using an isotope was applied to patients in a painless testing situation. It was also simple enough to be performed at any clinic equipped with a renogram apparatus. These results require verification by further studies on a larger number of patients.
An attempt was made to inhibit the rejection of renal allotransplants by use of the donor bone marrow. The survival time of untreated control dogs averaged 9.0±1.1 (S. D.) days, ranging from 7 to 10 days. Some prolongation of survival was achieved when azathioprine was given by mouth in a dose of 5 mg per kg per day for a week before and after renal transplantation and then 3 mg of the agent per kg per day. This group showed a mean survival of 17.5±5.2 days. All the transplanted kidneys showed typical features of allograft rejection. The survival time of the dogs given the donor bone marrow alone once before transplantation averaged 5.4±3.1 days, ranging from 4 to 7 days. On the other hand, the survival time of dogs which received azathioprine and allotransplantation of the donor bone marrow averaged 28.9±6.4 days, and that of the dogs which received azathioprine and allotransplantation of the non-donor bone marrow averaged 14.9±5.1 days. When the recipients were injected repeatedly with the donor bone marrow after transplantation, the mean survival time was prolonged to 37.0±5.3 days. Bone marrow was labeled in vitro with 3H-thymidine to trace the cells after injection into recipients; the presence of labeled band and segmented forms showed that injected cells were capable of both mitosis and maturation. By reaction of rabbit antiserum to canine erythrocytes, the life span of erythrocytes originating from the infused bone marrow cells in the peripheral blood of recipients was estimated, and it was shown that the survival time of kidney grafts was parallel to that of donor bone marrow. The effectiveness of the treatment with donor bone marrow combined with azathioprine as a conditioning agent was demonstrated on canine renal allografts.
Seventy-four dogs received renal allografts after simultaneous bilateral nephrectomy. Five recipients were untreated, another five were given daily subcutaneous injections of normal rabbit serum, twenty-five received daily injections of rabbit-anti-dog antilymphocytic serum (ALS) at varying intervals before and after transplantation, ten were treated daily by mouth with azathioprine, fourteen received daily injections of ALS combined with azathioprine, and fifteen were treated with daily injections of ALS combined with both azathioprine and the allotransplantation of the donor's bone marrow. The mean survival time of the untreated control animals and that receiving normal rabbit serum were 9.0±1.0 and 10.0±0.3 days, respectively. No animals in these groups survived more than eleven days. In the ALS-treated dogs, some prolongation of survival was achieved when the serum was administered subcutaneously twice a day in a total dose of 1.0 ml per kg per day from 4 days before renal transplantation to 14 days after the transplantation and then once a week, and the survival time averaged 20.9±2.7 days. On the other hand, azathioprine combined with ALS and allotransplantation of the donor's bone marrow produced a mean survival of 38.4±4.7 days, a significant prolongation of functional survival over those of the other series. Accordingly, a considerable synergism was found in the combined therapy with ALS, a small dose of azathioprine and allotransplantation of the donor's bone marrow.
Erabutoxin B, a toxic protein obtained from venom of Laticauda semifasciata, exerted a blocking effect on frog nerve-muscle preparation. This toxin reduced the irritability of the muscle cell and decreased tension developing in response to direct stimulation. By indirect stimulation, the ‘effective time’ was linear to the concentration of erabutoxin B in the range of 10-5 to 10-6. In microelectrode study, both the action potential and endplate potential were found diminished by erabutoxin B. The resting membrane potential was not affected. The effective membrane resistance was decreased. The action of erabutoxin B was considered to be a summation of blocking at the presynaptic site and direct action on the muscle cell membrane.
The postoperative results of 34 cases of chronic pancreatitis were evaluated in reference to different surgical operations. They comprised those of side-to-side pancreaticojejunostomy in 12 cases, distal pancreatectomy in 7, pancreatoduodenectomy in 5, pancreatolithotomy in 4 and other operative procedures in 6. In the overall assessment after a long-term follow-up, good results were found in 18 cases. When cases of immediate postoperative death and 2 cases of pancreatic cancer detected at operation were excluded, the above 18 cases made 62% of 29 operated cases. The best result was obtained by the side-to-side panereaticojejunostomy, 8 patients out of 9 having returned to normal life. Fat absorption was not favorably influenced by the operation, in contrast to remarkable relief of pain. There was a certain limit to the beneficial effect of surgical operations in patients with advanced pancreatic lesion.
The radii of the splenic and proper hepatic arteries were estimated by means of selective celiac arteriography in cases of portal hypertension and of splenomegaly without portal hypertension. The results were evaluated in comparison with normal arteriograms. The estimated radii of the splenic arteries were in satisfactory agreement with the histometrical ones. It was concluded that the splenic and hepatic arterial flow could be proportional to the 2.7th power of the radii of the respective arteries on arteriograms, as in the histometrical study.1, 2 In cases of portal hypertension and appreciable increase in the radius of the splenic artery was demonstrated. In splenomegaly without portal hypertension, as in idiopathic thrombocytopenic purpura, hemolytic jaundice, such an increase in the radius of the splenic artery was not observed. In portal hypertension, the radius of the splenic artery could be correlated with the splenic weight, portal pressure, the grade of decrease in the portal pressure after splenectomy and the length of the splenic artery. In cases of liver fibrosis, dilatation of the splenic artery was not usually accompanied by dilatation of the proper hepatic artery, whereas in liver cirrhosis with or without giant splenomegaly, dilatation was noted not only in the splenic artery but also in the proper hepatic artery as well.
In a patient with hyperalaninemia and hyperpyruvicemia previously reported, the levels of both pyruvate and lactate in the cerebrospinal fluid were found to be higher than those in the patient's blood, this suggesting that there may be a defective activity of pyruvate carboxylase in the brain tissue.
The prominent growth-promoting effect of serum albumin fraction V was hardly observable when purified crystalline serum albumin was employed, suggesting that the chemical factor respons;ble for the activity may belong to small molecular substances bound to albumin preparation as impurity. Minute amounts of linoleic acid did not show any growth-enhancing effect and the defatted preparation exhibited the activity just like the original albumin preparation did. Fetuin exhibited a growth-promoting effect for ‘A’ cells at the 28th transfer. Egg albumin showed growth-enhancing effect for the same cells under the same condition but the activity could not be observed when albumin was replaced with crystalline one. The active component (s) was proved to be heat-stable and dialysable.
Using various albumin fortified medium, many neonatal hamster lung cells were developed into established lines. The optimal culture condition to evolve into cell lines was investigated by varying the source of albumin, concentration of serum, inoculum density, medium component and time interval. Also, the minimum culture condition necessary to sustain the serial culture was examined. The requisite in the culture condition for the development of established cell lines was discussed.