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Surface induced deep hypothermia combined with cardiopulmonary bypass (combined method) is excellent in open heart surgery of infants which combines each advantage of cardiopulmonary bypass and hypothermia. The present study was performed to investigate pathophysiological changes, especially metabolic changes, in combined method induced by two stressors such as cardiopulmonary bypass and hypothermia. In general, metabolic changes during hypothermia are temporarily enhanced immediately after the start of cardiopulmonary bypass. Lactacidemia and metabolic acidosis are rapidly improved after the start of perfusion rewarming, but abnormality of ceruloplasmin and cholesterol metabolism in the liver and hypopotassemia are not rapidly improved. Therefore, the treatment for these metabolic abnormalities seems to be necessary during and after the procedure.

The effects of large doses of angiotensin II on the rabbit kidney and heart and or the ability of perfused canine kidney to inactivate angiotensin II were examined to clarify the role of angiotensin II in the low cardiac output syndrome after open-heart surgery. Intravenous infusion of angiotensin II at a rate of 1.1 to 1.4 microgram/Kg/min for 48 hours caused multifocal myocardial necrosis and renal mononuclear cell infiltration and necrosis. Isolated canine kidney preparations inactivated 76% of angiotensin I and 79% of angiotensin II. The results indicates that the kidney can inactivate angiotensin and that high doses of angiotensin II can produce myocardial and renal lesions. It is suggested that an increased concentration of angiotensin II may result in the low cardiac output syndrome through myocardial damage, and that decreased inactivation of angiotensin II by the kidney accelerates the myocardial damage.

One hundred and seven patients with ventricular septal defect who survived one and a half to thirteen years after hypothermic open-heart surgery were reviewed with respect to somatic, intellectual, and psychomotor development. There were no negative effects associated with deep hypothermic arrest in any of these areas. Abnormal electroencephalograms were seen in one-half the number of patients examined, but there was no close relation between the circulatory arrest period and electroencephalographic findings. CT scanning of the brain indicated that the abnormality decreased with the lapse of the time after hypothermic open-heart surgery. It would appear that hypothermic open-heart surgery with limited circulatory arrest is a useful method, providing that the circulatory arrest is not allowed to exceed a limited period. However electroencephalographic assessment suggests that postoperative cerebral abnormalities may occur more frequently than previously suspected, despite the lack of preoperative abnormalities on the electroencephalograms.

In surface-induced deep hypothermia, metabolic acidosis resulting from lactacidemia was observed. In the hypothermic heart, the rate of reduction in the coronary arteriovenous (A-V) difference ratio of lactate, pyruvate, and nonesterified fatty acids (NEFA) was proportionately less than that of coronary flow and myocardial oxygen consumption, suggesting that lactate, pyruvate, and NEFA play important roles as energy fuels in the hypothermic heart. Myocardial metabolism of glucose was reduced; exogenous corticosteroids and ATP do not influence the myocardial metabolism of carbohydrates and lipids in the hypothermic heart.

The role of the liver in the changes of acid-base balance and plasma lipids in surface-induced deep hypothermia for open-heart surgery was investigated clinically and experimentally. The metabolic acidosis generally observed in open-heart surgery under surface-induced deep hypothermia is derived from lactacidemia. Although the accelerated anaerobic glycolysis is partly responsible, the depressed acidic metabolite-disposing ability of the liver also plays an important role. The evidence which is presented to show the decrease of plasma lipids other than NEFA under hypothermia is probably due to the hepatic accumulation of lipids and the decreased lipids release from the liver.

In order to clarify the inhibitory mechanism of insulin secretion associated with open-heart surgery, the influence of insulin antagonistic hormones on insulin secretion was studied in 20 patients with congenital heart diseases undergoing open-heart surgery, under simple deep hypothermia. Despite a hyperglycemia, plasma immunoreactive insulin and C-peptide showed no change during the cooling period, while with the exception of plasma human growth hormone, dopamine-beta-hydroxylase, immunoreactive glucagon, cortisol and cyclic AMP in plasma, either showed no change, or a decrease during the cooling period. It is assumed that catecholamine, glucocorticoid and glucagon do not play an important role in the inhibitory mechanism of insulin secretion during hypothermic open-heart surgery, and a transient hypofunction of the pancreas as well as the liver and the adrenal gland is probably involved.

We constructed recombinant vaccinia viruses (RVVs) that expressed human T-cell leukemia virus type I (HTLV-I) envelope glycoproteins by using attenuated vaccinia viruses (VVs) which have much lower neurovirulence than the WR strain that is extensively used as a vector. The RVV produced from the LC16mO strain, one of the attenuated VVs, elicited a high titer of anti-HTLV-I antibody in rabbits and protected them against HTLV-I infection. The env gene was inserted into the VV hemagglutinin gene. The resultant inactivation of the hemagglutinin gene led to the attenuation of VVs, but the extent of their attenuation depended on the VV strain. The propagation of LC16mO and its RVV in rabbit brain was poorer than that of LO-1, a cloned derivative of Lister strain, and its RVV, although LC16mO replicated in other organs better than did LO-1. Taken together, these results suggest that LC16mO is a good candidate as a vector for vaccination of humans.

The posttranscriptional regulator (p27x-III) of human T cell leukemia virus type I (HTLV-I) is located predominantly in the cell nucleolus. A highly basic amino-terminal sequence (NH2-Met-Pro-Lys-Thr-Arg-Arg-Arg-Pro-Arg-Arg-Ser-Gln-Arg-Lys-Arg-Pro-Pro -Thr- Pro) in this protein, when fused to the amino termini of beta-galactosidase and p40x of HTLV-I, acts as an autonomous signal capable of directing the hybrid proteins to the cell nucleolus.

A total of 31 cases of Crohn's disease; 23 males and 8 females; 8 small bowel, 11 colon, 8 both small and large bowels involvement and 4 unknown, were collected and analysed. Twelve cases were treated medically and 19 were operated with 61% of operative and 37% of reoperative rate. There was no death due to Crohn's disease. IVH was successful as non-surgical treatment. Indications for surgery were stricture, fistula formation and unsuccessful medical treatment. Limited resection of the diseased segment was performed and in 4 cases diseased segment was left behind without significant postoperative symptoms. Quality of life of the surgically and medically treated patients was satisfactory except one who had many operations during 20 years and still suffers from Crohn's disease. In 15 (48.4%) periproctal abscess or fistula was associated. There were 2 types of anal lesions, the one being ordinary type of low intersphincteric abscess or fistula and the other complex or Crohn's disease related high abscess or fistula. The former was successfully treated by laying-open whereas the latter was treated rather conservatively by drainage not to damage external sphincter muscles. Outcome of medical and surgical treatment of Crohn's disease was quite satisfactory and operation should not be hesitated in patients with serious complications. Type of anal lesion is to be identified and proper surgical treatment should be performed in feasible cases.

Recombinant vaccinia virus (RVV) containing the full-length cDNA of rinderpest virus (RV)-haemagglutinin (H) gene was constructed. The H gene was inserted into the attenuated vaccine strain of vaccinia virus (VV), Le 16 m0, with two different promoters, namely cowpox virus A-type inclusion body (ATI) promoter or VV 7.5 kilodalton (P7.5) promoter. These RVVs produced the same sized fully glycosylated RV-H protein in RK 13 cells as that of the authentic RV-H. Their heat stability in the lyophylized state was similar to that of the parental VV. All rabbits immunized with these RVVs produced virus neutralizing (VN) antibody to RV as well as anti RV-H antibody. Four weeks after immunization, these animals were challenged with RV intravenously. None of the RVV-immunized rabbits developed any clinical signs of RV infection except one which was immunized with RVV containing the ATI promoter and developed low VN titer. These results indicate the possibility of developing a heat-stable recombinant vaccine for the eradication of rinderpest in tropical countries without cold storage systems.