Obstructive jaundice in patients with pancreatitis without associated biliary tract disease. Jaundice occurring in patients with pancreatitis is usually due to hepatocellular injury or to associated biliary tract disease. Common duct obstruction is occasionally caused by pancreatic fibrosis, edema or pseudocyst in patients who have neither hepatocellular injury nor biliary tract disease. We have studied 7 patients with obstructive jaundice due to pancreatitis who demonstrated no other known cause for jaundice. The difficulty in making the differential diagnosis between benign and malignant disease in these patients, particularly when no pain is associated with obstructive jaundice, is discussed. In view of the fact that the terminal common duct traverses the pancreas, it is uncertain why obstructive jaundice associated with chronic pancreatitis does not occur more often unless the condition is sometimes transient and overlooked. Operative intervention is required in those patients in whom jaundice is persistent. Operation is intended to decompress the biliary tract and the pancreas. The approach used will be dictated by the operative findings in each patient.


Postoperative adrenal hemorrhage.

Postoperative adrenal hemorrhage. Twelve elderly patients without Waterhouse-Friderichsen syndrome or adrenal tumor who had spontaneous adrenal hemorrhage one to 33 days after operation are described. Seven of these patients had operations on the gastrointestinal tract, one on the biliary system, two on the genitourinary system and two on the central nervous system. Important factors relating to adrenal hemorrhage included: intra-abdominal sepsis in 5 patients, cancer in 4, pneumonia in 4, coagulation defects in 2, exogenous steroids in 2, and syphilis in one patient. Spontaneous adrenal hemorrhage should be considered in patients whose condition deteriorates rapidly after operation and in whom no other explanation is plausible. Its detection and appropriate therapy can be lifesaving.


An evaluation of the application procedure for surgical house officership. The application procedure for surgical house officership was evaluated at 25 university affiliated surgical training programs. Major inadequacies were found with the present system. The prospective house officer often does not receive relevant, up-to-date or useful literature, and interviews and tours were frequently conducted in a haphazard manner. Recommendations are offered to improve the application process and criteria are provided, which should assure adequate levels of information and help the candidate arrive at an appropriate decision with regard to postgraduate training.


Left-sided gallbladder:: calculous cholecystitis with situs inversus. A 59-year-old woman with complete situs inversus, developed cholecystitis in a left-sided gallbladder. The diagnosis was made radiologically and a successful operation performed. A diseased gallbladder containing two calculi, together with the appendix, was removed. An operative cholangiogram revealed a normal, but transposed, biliary system. The literature on this subject is reviewed.


A small arterial substitute: expanded microporous polytetrafluoroethylene: patency versus porosity. Eighty-nine grafts of expanded microporous polytetrafluoroethylene (PTFE) with a diameter of 4 mm, were placed in the carotid and femoral arteries of dogs. The animals were sacrificed at varying intervals beginning three days after operation. Four animals remain alive with patent grafts 10 months post-operatively. Twenty-four of 89 grafts were occluded, an overall patency of 73%. Fibril length (pore size) of the graft material was varied from 4 to 110 microns. Average pore size ranged from 9 to 65 microns. Wall thickness varied from 0.3 to 0.75 mm. Density ranged from 0.24 to 0.35 g/ml. Tissue ingrowth, neointimization and patency rate as compared to pore size, wall-thickness and density of expanded PTFE were observed. Pore size is the primary determinant of tissue ingrowth, neointimization and patency. Of 51 grafts with an average pore size of 22 microns or less, there were 6 occlusions, an 88% patency rate. There were 38 grafts with an average pore size of 34 microns or greater. In these 38 grafts, 18 occlusions were observed, a 53% patency rate. Patent grafts demonstrated tissue ingrowth, capillary formation an a thin neointima. Using small pore grafts, patency rates of 90% can be anticipated in the dog. Expanded microporous PTFE with its ease of handling, strength and pliability may be the vascular prosthesis of choice in man.


Prevention of infection in war chest injuries. Infection is a major complication of military chest injuries. In a series of 142 wounded, infectious complications occurred in 7 (4.9%). Factors influencing the incidence of infection are evaluated. In this group of injuries, 81 patients were admitted soon after wounding. The intrathoracic damage was severe, due to penetration of metallic fragment. The hemothorax was treated by immediate intercostal drainage. Immediate thoracotomy was performed in 10 patients and late thoractomy in 15. One patient developed a lung abscess and 5 patients had infection following thoracotomy (7.4%). Another 61 wounded patients had been first managed in a forward hospital, including three with thoractomy for massive bleeding. Two, not in a forward hospital, had a bullet removed from the lung. Upon admission to this hospital, intercostal drains were inserted when needed and four patients underwent thoracotomy. Larger wounds were debrided in 24 patients. Late thoracotomy was perfromed in seven. Chronic empyema developed in one patient after pneumonectomy performed at the field hospital, resulting in a resuscitation or infection rate of less than 2%. Factors contributing to a low infection rate were: early drainage of hemothoraces and wide debridement of larger wounds with delayed closure and avoidance of thoracotomy as primary treatment. Resection of lung tissue was avoided. Thoraco-abdominal injuries were treated separately. The clotted hemothorax was immediately evacuated. Prolonged antibiotic therapy was usually indicated.


Prolonged secretion of lithogenic bile after cholecystectomy. Hepatic bile samples were obtained from 8 subjects 1 1/2 to 23 years after cholecystectomy for presumed cholesterol gallstones. The content of cholesterol, bile acids and lecithin was determined for each bile sample and compared to the values found in gallbladder bile in 15 control subjects undergoing cholecystectomy for pure and mixed cholesterol stones. Plot of the data on triangular coordinates and subsequent determination of lithogenic index showed that bile was supersaturated with cholesterol in both groups of patients. The cholesterol content of bile remained at supersaturated levels following cholecystectomy and showed no tendency to return toward normal levels with the passage of time.


Reversed gastric tube (RGT) esophagoplasty for failure of colon, jejunum and prosthetic interpositions. Reversed gastric tube (RGT) esophagoplasty is preferred by the author as the primary procedure for esophageal replacement. Many patients undergoing RGT esophagoplasty, however, have previously had multiple operative procedures. A particularly challenging problem in esophageal reconstruction is the patient who has already had unsuccessful intestinal or prosthetic interposition operations in attempts to reconstruct the esophagus. In such patients, it has been possible to replace the esophagus by means of the RGT operation. Of 67 RGT esophagoplasties, 9  patients (13.4%) had previous interposition operations that had failed. Six had undergone colon interposition; 2 of these had strictured, 1 had partially sloughed leaving a cervical salivary fistula, and in 1 the proximal end was never patent. In each instance, bypass with RGT was performed without resecting the colon transplant. The colon had necrosed and was removed in 2 patients. Of the remaining 3 patients, in 1 a plastic esophageal prothesis had sloughed and two had free jejunal transplants, 1 of which had impaired vascularity and the other had fibrosed. The specific techniques used to reconstruct the esophagus by reversed gastric tube esophagoplasty, as they relate to this particular group of patients, are described.


Femoral neuropathy and ischemic colitis associated with amyloidosis in hemodialysis patients. Renal failure is often the presenting problem with amyloidosis and it portends a generally poor prognosis. Two of 121 patients in a home dialysis program were found to have amyloidosis after they developed unusual complications, ischemic colitis and femoral neuropathy. Both ultimately died as a result of their disease. From the limited experience that is reported, it appears that renal transplantation offers a better alternative for long term therapy than hemodialysis.


Successful treatment of hepatic artery aneurysm with erosion into the common duct. A patient with an hepatic artery aneurysm is presented with preoperative angiographs, and intra-operative photographs demonstrating erosion and fistulazation into the common duct. The aneurysm was ligated and excised, and the erosion of the common duct was treated successfully with a Roux-en-Y choledochoduodenstomy. This is the fourth case with erosion into the common duct to be treated successfully by surgery. The other three cases are discussed. A review of the literature reveals that hepatic artery aneurysms are rare, and successful treatment is based on several different techniques. Ligation of the hepatic artery, with or without excision of the aneurysm, is discussed as a method that may in fact be the safest treatment in a group of patients who because of their disease are already in a high risk category.


Goiter and deaf mutism.

Goiter and deaf mutism. The occurrence of deaf-mutism and goiter unassocaited with creatinism or mental retardation in euthyroid patients is known as Pendred's Syndrome. It is considered due to a single mutant recessive gene responsible for both the goiter and deafness. The penetrance is high, the intenseness of expressivity may vary within the same family and only one generation is affected. The extremely atypical hyperplasia seen in such goiters has been considered malignant. In 1956 the author reported a family in which 4 of 6 sibilings demonstrated Pendred's Syndrome. Three of the 4 had undergone thyroidectomy, two were considered to have carcinoma. Nineteen years later the family is again reported. The fourth sibling has recently undergone thyroidectomy. This thyroid demonstrated the same atypical hyperplasia as seen in the elder two siblings. The 19 year followup of this family has shown no evidence of recurrence or metastases, indicating that the atypical hyperplasia is probably not malignant. Pendred's Syndrome is described and certain suggestions are made for the counseling of the parents and the treatment and counseling of those children so afflicted.


Effect of nutrition, diet and suture material on long term wound healing. Although it is known that malnutrition hinders early wound healing, it has not been determined whether this occurs because of formation of a poor scar or a slow rate of normal healing; the ultimate fate of the malnourished wound is unknown. Malnutrition was produced in rats by short gut syndrome. Elemental diet was compared to rat chow and silk was compared with polyglycolic acid suture. Nutritional deficiency was seen in short gut rats for two weeks postoperatively. Thereafter adaptation allowed partial recovery, but relative deficiency persisted. Morbidity and mortality of short gut rats doubled that of controls and all wound complications were limited to this group, occurring within the first two weeks. Malnourished animals surviving for 60 days had wound strength equal to the control rats as determined by gut anastomosis bursting strength, skin wound breaking strength and wound hydroxyproline content. Neither diet nor suture material altered ultimate wound strength. Improved nutrition allowed more animals and wound to survive, but ultimate healing survivors was indistinguishable from that of normal controls. Thus early weakness probably results from slow healing rather than formation of poor scar. Nutrition plays an important role in early strength and survival, but not in ultimate wound healing.


Noninvasive cardiac evaluation (NICE) of intracardiac shunts using inhaled radioactive carbon dioxide. A totally new, noninvasive technique is presented for the detection and analysis of left-to-right cardiac shunts. Five millicuries of oxygen 15-labeled carbon dioxide is administered by a single-breath inhalation technique. The resultant lung washout curve accurately reflects the presence or absence of a shunt. The quantitative studies are promising, but the method must be compared with standard techniques in a statistically significant series. This work is in progress.


The role of intraaortic balloon counterpulsation in patients undergoing cardiac operations. Intraaortic balloon counterpulsation (IABC) was used to assist 60 patients undergoing cardiac operations for reasons of acute left ventricular  failure (18 patients) or electively for indications in high-risk coronary and valvular heart disease (42 patients). Nine of 18 patients achieved hemodynamic stability when treated for acute perioperative or postoperative cardiogenic shock. Four of these died from problems unassociated with postoperative left ventricular failure and 5 were long-term survivors, indicating a potential salvage of 50%. In 42 high-risk patients, IABC was used electively to control preinfarction angina before operation (21 patients) and prophylactically to prevent postoperative low-output failure in another 21 patients with severe coronary and valvular heart disease. Thirty-nine, or 93%, of these patients survived. There were no deaths in the preinfarction angina group, 1 death in the group with coronary disease and ejection fractions less than 30%, and 2 deaths in those with valvular heart disease and congestive failure. Seven patients developed thrombotic or ischemic complications, but no permanent damage resulted. IABC is an important form of assistance for any patient with preoperative, intraoperative, or postoperative left ventricular failure and adds safety and hemodynamic stability for the high-risk patient with preinfarction angina or poor ventricular function.


The effect of cardiopulmonary bypass perfusion pressure on myocardial gas tensions in the presence of coronary stenosis. Mass spectrometry was utilized to determine myocardial gas tensions in dogs subjected to cardiopulmonary bypass. Myocardial ischemia occurred in animals with normal coronary arteries when cardiopulmonary bypass perfusion pressure fell 40 to 60 mm Hg below the mean aortic pressure measured prior to bypass. Myocardial ischemia did not occur, or could be eliminated when present, if cardiopulmonary bypass perfusion pressure was maintained near prebypass mean aortic pressure. In animals with constricted circumflex coronary arteries, the adverse effect of low perfusion pressure on myocardial metabolism during cardiopulmonary bypass was found to be more severe in areas of myocardium supplied by the stenotic coronary artery. It is concluded that maintenance of cardiopulmonary bypass perfusion pressure near the level of preoperative mean aortic pressure will help prevent myocardial ischemia during operation; particularly in patients with coronary artery disease.


Is mediastinoscopy necessary in the evaluation of lung cancer? The records of 96 consecutive patients who underwent mediastinoscopy and were ultimately shown to have bronchogenic carcinoma were reviewed. Indirect tests for mediastinal tumor metastases in these patients included bronchoscopy and chest roentgenograms in all 96, mediastinal laminagrams in 65, esophagograms in 27, carinal biopsy in 23, bronchograms in 5, pulmonary angiograms in 5, azygograms in 2, and aortograms in 2 patients. Of the 43 patients in this series in whom all indirect tests revealed no metastases, mediastinoscopy showed nodal involvement in 11 (28%), who were thus spared unnecessary thoracotomy. On the other hand, if negative mediastinoscopy had not cast doubt on the validity of indirect tests that seemed to show metastases, an operation might actuallly have been denied to 14 patients who were ultimately proved to have anatomically resectable disease.


Coarctation of the abdominal aorta with multiple aneurysms. Operative correction. An 11-year-old asymptomatic girl with hypertension was found to have coarctation of the abdominal aorta with four aneurysms in or adjacent to the hypoplastic segment of aorta. Operative treatment included insertion of a thoracoabdominal aortic bypass graft and resection of the aneurysms. The association of abdominal coarctation and aneurysm formation is reviewed and the rationale for therapy discussed.


A method for revascularization of circumflex marginal coronary arteries. The transverse sinus route for bypassing high marginal circumflex coronary arteries facilitates the operation and obviates potential kinking sites at the left atrial appendage and pericardial reflection over the pulmonary veins. The vein bypass emerges from the transverse sinus and closely parallels the marginal circumflex coronary vessels.


Internal mammary--coronary artery anastomosis. "No-touch" technique. A simple technique for internal mammary--coronary artery anastomosis that can be applied to all branches of the coronary circulation is described. The anastomosis can be constructed in 10 to 15 minutes. This technique eliminates pinching of the internal mammary artery by forceps.


Correction of truncus arteriosus after pulmonary artery banding. Correction of truncus arteriosus can be performed in the older child with low mortality. However, many infants are severely symptomatic with increased pulmonary blood flow and require banding of the pulmonary artery at an age when correction has a high mortality. The pulmonary artery band can complicate the usual technique of the subsequent repair. An alternative approach following pulmonary artery banding is to interrupt the pulmonary artery--truncus continuity with a patch from within the truncus and then place the external valved conduit onto the pulmonary artery in an end-to-side manner.


Norepinephrine content of various rat organs after chronic administration of desmethylimipramine. The effect of chronic oral administration of desmethylimipramine (DMI) on the norepinephrine (NE) content of various organs was examined in rats. The present results show that in contrast to its effect on the brain, where it lowered the NE concentration, chronically administered DMI either did not change (vas deferens) or tended to increase (heart and spleen) the NE concentrations in the examined peripheral organs. The effect of chronic DMI administration on the brain seems to be specific since this was the only studied organ in which a decreased NE concentration was observed.


Effect of cyanoketone on digitoxin-induced mortality and hepatic mixed function oxidases in rats. Cyanoketone pretreatment protected female rats against digitoxin-induced mortality. Cyanoketone also acts as an inducer of hepatic mixed function oxidases, increasing cytochrome P-450 content and enhancing aniline hydroxylase and aminopyrine demethylase activities. The protective effect of cyanoketone against digitoxin toxicity may be due to the enhanced conversion of the glycoside to more polar metabolites which are more readily excretable.


Suppression of Cerebellar Evoked Potentials by a peripheral action  of diphenylhydantoin. Cerebellar evoked potentials were produced by muscle stretch, increased muscle tension and direct stimulation of axons originating  in muscle nerves. Diphenylhydantoin, 10 mg/kg, suppressed only the cerebellar potentials evoked by muscle stretch indicating a suppression of muscle spindle function leading to a reduced cerebellar input. With larger DPH doses (total 60 mg/kg) cerebellar evoked responses produced by any of the above forms of stimulation were depressed indicating an impairment in the CNS. The data indicate that peripheral suppression of muscle spindles contributes to the cerebellar deficits observed in intoxication with diphenylhydantoin.


Antagonism of barbiturate by DNA pyrimidines and allied compounds. The mortality caused by barbiturate poisoning in mice is reduced by the combined action of the DNA pyrimidines thymine and 5-hydroxymethylcytosine (5-HMC) and the structurally related vitamins, pyridoxal, nicotinamide and thiamine, given intraperitoneally. The acute hypnotic effect of sodium pentobarbital at moderate to high dosages is also antagonized by these compounds. All five compounds are required for activity. The structural similiarity between these antagonist components and the barbiturates had suggested that the former's reactions as cofactors or as the constituents of more complex molecules might be points of drug inhibition. It therefore appeared that this inhibition might be reversed by administration of these cellular constituents. The obligatory requirement for both thymine and 5-HMC as components of this antagonist raises the possibility that a metabolically reactive DNA species in brain may be one site of barbiturate action. At the dosages employed, this antagonist produces no behavioral or symptomatic response in non-narcotized animals and may thus provide a basis for treatment of barbiturate poisoning.


Influence of halothane on calcium movements in isolated heart muscle and in isolated plasma membranes. The influence of halothane on cellular calcium movements was studied in guinea-pig isolated atria and in isolated plasma membrane from guinea-pig myocardial muscle. In spontaneously beating atria halothane (1.6 X 10(-4) M) significantly reduced the rate of 45Ca-accumulation, but the total tissue calcium content and the exchangeable fractions remained unchanged. In isolated plasma membranes the rate of 45Ca- uptake was increased by halothane. Moreover, the binding capacity for calcium was increased as well upon exposure to halothane in concentrations that are sufficiently elevated to depress cardiac contractile force. This finding is interpreted in the sense of a reduced amount of ionized calcium that can be made available for excitation-contraction coupling, owing to the halothane- induced acceleration of calcium binding by plasma membranes. Kinetic experiments in isolated atria had already suggested that halothane probably acts at the level of the outward cell membrane. The changes in membraneous calcium migration may be causally related to the cardiodepressive influence of the anaesthetic agent.


Effects of ethanol and its interaction with vasoactive agents in bovine vascular smooth muscle. The vascular effects of ethanol were evaluated using isolated arteries from bovine brain, eye, and kidney. Ethanol induced contraction in all vessels, but only at concentrations in excess of lethal blood levels in man. At a concentration approximating that found in the blood during intoxication (43 mM), ethanol had no effect on renal vascular responses to norepinephrine, serotonin, or histamine. The response of ocular vessels to norepinephrine and histamine was significantly diminished by 43 mM ethanol, suggesting a possible mechanism underlying the "bloodshot" eyes found in acute intoxication. Cerebral vascular responses to vasoactive agents were generally unaffected by 43 mM ethanol, indicating that regional differences in brain perfusion are probably not a cause of the behavioral changes found during intoxication.


Synthesis and adrenergic neuron blocking properties of some alkylating analogues of bretylium. A series of ortho-substituted N-alkyl-N-(2-chloroethyl)-benzylamines have been prepared. These compounds are structurally similar to the adrenergic neuron blocking agent bretylium. They were tested for neuron blocking activity using both the innervated rabbit jejunum and the vas-deferens-hypogastric nerve preparation of the guinea pig. Three compounds possessed some adrenergic neuron blocking activity of a prolonged nature, the most potent being N-(2-chloroethyl)-N-(0-bromobenzyl)-ethylamine.


Effect of glucagon on myoelectrical and mechanical activity recorded from the isolated homologous perfused canine stomach. Totally isolated whole canine stomachs, perfused ex vivo with homologous blood, were used for recording of myoelectrical and mechanical activity. Hormones were administered into the arterial system of the isolated stomach. Pentagastrin, methacholine and electrical stimulation induced premature control potentials with uncoupling of the normal, phase locked, pattern of electrical control activity and also stimulated mechanical activity. Electrical response activity was also present. When the three modes of stimulation were applied during the infusion of glucagon, a marked inhibitory effect was observed. This effect consisted of inhibition of mechanical activity and of electrical response activity. Glucagon also decreased, but did not suppress the changes in electrical control activity observed after electrical stimulation and after injection of pentagastrin or methacholine into the gastric artery of the isolated stomach. During infusion of glucagon, the mean gastric arterial perfusion pressure and gastric peripheral vascular resistance were reduced.


Direct renal hemodynamic effects of clonidine. The renal hemodynamic and excretory effects of clonidine were tested in 2 groups of dogs. In one group, the drug was given directly into the renal artery at a rate of 1.2 mug/min and resulted in a significant decrease of the effective renal plasma flow (ERPF) in both kidneys, an increase in filtration fraction (F.F.), urine volume (U.V.), and free water clearance (CH2O) and had no effect upon the glomerular filtration rate (GFR), osmolar clearance (Cosm) and the excretion of sodium (UNa+V), chloride (UC1-V), potassium (UK+V), calcium (UCa++V) and phosphorous (UP04V). In the second group of animals it was given intravenously at a rate of 12.0 mug/min and resulted in a significant decrease of ERPF, UNa+V, UC1-V, and an increase in F.F., U.V. and CH2O and had no effect upon GFR, Cosm, UK+V, UCa++V and UPO4V. Systemically, it decreased heart rate (H.R.) and respiratory rate (R.R.) in both groups of animals; it increased blood pressure (BP) in Group I and had no effect on BP in Group II.


Effects of metiamide on distribution of 14C-histamine in aortic smooth muscle. The effects of metiamide on 14C-histamine movements and on contractions induced by histamine were studied in rabbit aortic smooth muscle. Low temperature (0 degrees C) and pretreatment with aminoguanidine or chloroquine markedly reduced the uptake of 14C. Component analysis of 14C efflux curves indicated that this decrease occurred mainly within the slower of two washout components. Addition of metiamide (but not pyrilamine) to the bathing solution decreased 14C-histamine uptake, and exposure to metiamide during the washout of 14C-histamine decreased the rate of efflux. These effects of metiamide on 14C-histamine movements can be explained in terms of an altered ability of rabbit aortic smooth muscle to accumulate histamine at some cellular site or store.


Influence of catecholaminergic agents on narcotic binding in brain. The effects of various agents on the specific tissue binding of 3H-naloxone and 3H-naltrexone were examined. In addition to the narcotics, alpha-adrenergic blockers and dopamine antagonists also significantly inhibited the specific bindings of these opiates. The binding of naloxone or naltrexone was not significantly altered by beta-adrenergic blockers, agents which block the effects of acetylcholine, serotonin and histamine at the receptor level, and a number of other drugs. Kinetic analyses revealed that the alpha-adrenergic and dopamine antagonists competitively inhibited the binding of naloxone. The results of these studies provide additional evidence for an interaction between the narcotics and catecholaminergic agents.


The effects of drugs on accumulation and release of catecholamines in rat brain slices. Pretreatment of rats with reserpine decreased the uptake and release of labelled NE and DA in rat slices. MAO inhibition with nialamide partially antagonized the effects of reserpine, but nialamide itself decreased the release of labelled DA. Treatment of brain slices in vitro with phenoxybenzamine or desmethylimipramine inhibited uptake of catecholamines, and affected spontaneous and electrically-stimulated release in a manner consistent with the existence of an alpha-receptor-mediated feedback regulation of release at both NE and DA nerve terminals. The effect of phenoxybenzamine on stimulated release was observed to be dependent on stimulation rate.


Effect of amphetamine and apomorphine on brain monoamines and behaviour in the immature and young adult rat. In the immature rat (12-day old), amphetamine (10 mg/kg i.p.) caused an initial increase in forward locomotion, followed 15 min later by intermittent stereotyped behaviour (SB). Fifty to 65 min after injection the animals entered a phase of sleep which lasted 1-3 hrs; after this period continuous SB emerged, lasting 2-3 hrs. Brain amphetamine levels (half-life = 150 min) were elevated throughout the sequence of behavioural effects. Peak amphetamine levels were lower in the immature rat than in the adult rat. In the immature animal amphetamine caused a decrease in brain dopamine (DA) 4 hrs after injection and a sustained decrease in noradrenaline (NA) which was evident at 90 min and persisted throughout the study; a significant increase in serotonin (5HT) was evident at 15 min but had returned to normal at 90 mins. In the young adult rat (5-6 wks old), amphetamine caused an increase in forward locomotion, followed in 10-15 min by continuous SB lasting 4-4.5 hrs. The half-life of brain amphetamine was 66 min. Amphetamine increased brain DA and NA within 15 min of injection. At 90 min 5HT was elevated, DA had returned to normal but NA was still increased; thereafter the concentration of NA declined to significantly lower levels than controls and 5HT returned to normal. In the immature rat, apomorphine (10 mg/kg i.p.) caused an initial increase in locomotion which was followed 10 min later by transient intermittent SB. Following this, the animals entered a phase of sleep which lasted about 40 min before intermittent SB reemerged; this persisted for 1-2 hrs. Apomorphine caused an increase in NA and a corresponding decrease in DA at 15 and 30 mins after injection after which the levels of these amines returned to normal; 5HT levels were unchanged. In the adult rat SB commenced immediately after injection of apomorphine and lasted 70 min. There were no changes in levels of brain monoamines. There was no clear correlation between behavioural observations and levels of brain monoamines after amphetamine or apomorphine.


The narcotic cue: evidence for the specificity of the stimulus properties of narcotic drugs. Various non-narcotic drugs with intrinsic stimulus properties were found not to be generalized with fentanyl treatment in rats trained to discriminate fentanyl (0.04 mg/kg, s.c., t-30') from its solvent (s.c., t-30'). In contrast, five typical narcotic analgesics yielded dose-dependent generalization with fentanyl treatment. The results evidence the specific character of the narcotic cue in rats.


Influence of bile flow, theophylline and some organic anions on the biliary excretion of 3H-ouabain in rats. The influence of some organic anions and theophylline on the biliary excretion of 3H-ouabain in bile-fistula rats (treated with 55 nmoles X kg(-1) 3H-ouabain i.p.) was investigated. Compared with controls (31.5 +/- 1.6 nmoles X kg(-1) per 3 hr) the excreted amounts of the glycoside within 3 hr were decreased to the following values: 22.3 +/- 0.9 nmoles X kg(-1) by taurocholic acid (0.7 nmoles X kg(-1) X hr(-1); 25.6 +/- 1.7 nmoles X kg(-1) by sulfobromophthalein (0.15 nmoles X kg(-1); 19.3 +/- 2.0 nmoles X kg(-1) by phenolphthalein (0.5 nmoles X kg(-1) and 20.9 +/- 2.1 nmoles X kg(-1) by probenecid (1.5 nmoles X kg(-1). Taurocholic acid and probenecid increased the bile flow by about 50 per cent compared to the controls as well as the biliary excretion of Na+, K+ and Cl-. Ethacrynic acid (0.2 nmoles X kg(-1) and the phospho-diesterase inhibitor theophylline (1.1 nmoles X kg(-1) had no influence on bile flow, electrolyte-and ouabain excretion. Therefore no relation between the biliary transport of ouabain and the bile flow could be observed. The interference of the hepatic transport of ouabain with organic anions is discussed in view of the current concept of a specific hepatic transport for steroid compounds.


Alteration of drug pharmacodynamics by hyperlipidemia. Circulating lipid levels, when elevated, can alter the pharmacodynamics of lipophilic drugs presumably by acting as an additional storage depot for such drugs. Prostaglandin E1 (PGE1) and phenylephrine produced less effect on the blood pressure of atherosclerotic-hyperlipidemic rabbits than of control rabbits. This difference was apparently not due to alterations in vascular smooth muscle since aortic strips from the normal and severely atherosclerotic rabbit responded identically to the contractile effects of these drugs. Further, hyperlipidemic rats which had not yet become atherosclerotic were less responsive to the convulsant effects of fluorthyl, a highly lipophilic drug. In the presence of emulsified fat the contractile response of the rat ileum in vitro to PGE1 and acetylcholine was greatly reduced. The inhibition was reversed when fat was removed from the bathing solution. The response to PGE1, which is more lipid-soluble than acetylcholine, was more sensitive to inhibition by the presence of lipid. Finally, the pharmacokinetics of intravenously administered sulfamerazine, a lipophilic drug, appeared to be altered in the hyperlipidemic rabbit.


Response of normal subjects to a single 2-milligram dose of glucagon administered intramuscularly. Recently there has been increased interest in glucagon because in human radiographic and endoscopic studies it has been reported to relax the gallbladder, stomach, small bowel and colon. These results suggest it may be preferable as a diagnostic aid for these procedures. Therefore, we believed it important to assess the safety, and clinical laboratory responses after glucagon is given to normal subjects. Twenty normal subjects received 2 mg of glucagon and placebo intramuscularly at daily intervals, double-blind and crossover. After glucagon there was an increase in the WBC, bands, neutrophiles, fasting blood sugar, glucagon and insulin, and a decrease in the lymphocytes. There was no change in the pulse rate or blood pressure with minimal reports of side effects. These results tend to confirm other reports that glucagon is one of the stress hormones. Glucagon is remarkably safe and produces few, mild and transient side effects, not much greater than placebo.


[Effect of ingestion of derivatives of quinoxaline on the enzymatic detoxication activity of hepatic microsomes in the rat]. Female rats received quinoxaline, 2,3-dimethyl quinoxaline, 2,3-diphenyl quinoxaline and 2,3-dithiol quinoxaline by oral intubation for 4 days (500 mg/kg/day) and drug-metabolizing enzymes were investigated. A significant stimulation in liver microsomal enzymes occurred after 2,3-dimethyl quinoxaline and 2,3-diphenyl quinoxaline treatments; these changes were associated with increases in cytochrome P-450 level and in RNA and protein contents of the microsomal fraction. Quinoxaline had no effect on the metabolic rate of the studied substrates but increased the cytochrome P-450 and the RNA and protein levels; whereas, 2,3-dithiol quinoxaline inhibited the aminopyrine and N-methylaniline N-demethylations and decreased the cytochrome P-450 per mg microsomal protein.


Pharmacological and electrophysiological characteristics of neurones in the paramedian reticular nucleus. 1. Neurones in the paramedian reticular nucleus of decerebrate, unanaesthetised cats have been identified by microelectrode recording combined with antidromic activation of their axons in the ipsilateral inferior cerebellar peduncle. Most paramedian reticular neurones were not influenced by somatic stimulation. 2. When applied by iontophoresis from multibarrelled micropipettes acetylcholine and 5-hydroxytryptamine excited all but a few paramedian reticular neurones while l-noradrenaline inhibited almost all the neurones investigated. The excitatory response to acetylcholine could be antagonised by gallamine. 3. The paramedian reticular nucleus appears to be a relatively homogeneous group of neurones, pharmacologically as well as anatomically.


Response of Renshaw cells to sinusoidal stretch of hindlimb extensor muscles. 1. Renshaw cells responding disynaptically to electrically induced group I volleys in the intact gastrocnemius-soleus (GS) nerve, were submitted to small-amplitude, high-frequency vibration applied longitudinally to the deefferented GS muscle in precollicular decerebrate cats. 2. Vibration of the GS muscle at 200/sec, 180 mu peak-to-peak amplitude for 80-100 msec produced a sudden increase in the discharge rate of Renshaw cells, which gradually decreased within 25-50 msec to reach a steady level higher than that recorded in the absence of vibration. 3. Excitation of Renshaw cells appeared at a threshold amplitude of vibration (at 200-250/sec) of 5-20 mu and increased to a maximum value for amplitudes of about 70-80 mu, i.e., when all the primary endings of the spindles from the GS muscle had been driven by the stimulus. Recruitment of the secondary endings of the muscle spindles, due to large amplitude muscle vibration, did not modify the response of the Renshaw cells to the mechanically induced group Ia volleys. 4. These findings were obtained with the GS muscle pulled at 8 mm of initial extension. A threshold response of Renshaw cells to vibration appeared at 4 mm of static stretch, while maximal responses occurred at 8 mm. No further increase and actually a slight decrease in the response appeared for initial extensions of the muscle of 10-12 mm. 5. For a given vibration amplitude, the response of the Renshaw cells increased with increasing frequencies of vibration to reach the maximum at frequencies of 150-250/sec. Bursts of Renshaw cell discharges synchronous to each stroke of vibrator occurred only for low frequencies of stimulation (less than 25/sec). 6. It is concluded that vibration of the GS muscle represents a very effective method in exciting the Renshaw cells and that this response depends upon selective stimulation of homonymous motoneurons monosynaptically excited by the orthodromic volleys originating from the primary endings of the corresponding muscle spindles.


The relative sensitivity of Renshaw cells to orthodromic group Ia volleys caused by static stretch and vibrations of extensor muscles. 1. Activity of Renshaw cells monosynaptically excited by ventral root stimulation and disynaptically excited by electric stimulation of the group Ia afferents in the gastrocnemius-soleus (GS) nerve, was recorded in precollicular decerebrate cats. The response of these units to prolonged vibration applied longitudinally to the deefferented GS muscle was then compared with that elicited by static stretch of the homonymous muscle, for comparable frequencies of discharge of the group Ia afferents. 2. Small-amplitude vibration of the GS muscle at 200/sec for one second produced a sudden increase in the discharge rate of Renshaw cells, which gradually decreased within the first 100 msec of vibration to reach steady albeit lower level than that obtained during the first part of vibration. The response of the Renshaw cells during the first 100 msec of vibration (phasic response) and that elicited during the last 500 msec of vibration (tonic response) were evaluated for different frequencies of sinusoidal stretch. The mean increase in the firing frequency per imp./sec in the Ia afferents was also calculated using the total one-second period. 3. The response of Renshaw cells to muscle vibration increased with the frequency of vibration and, over the value of 10/sec, appeared to be linearly related to the frequency of the input, at least up to the frequency of 150/sec. Since vibration was of sufficient amplitude to produce driving of all the primary endings of muscle spindles, the responses were expressed as mean increases in the discharge rate of Renshaw cells per average impulse/sec in the Ia afferents. The discharge of the Renshaw cell increased on the average by 2.90 and 1.08 imp./sec per each imp./sec in the Ia afferents during the phasic and the tonic component of the response respectively, while the response calculated during the whole period of vibration corresponded on the average to 1.45 imp./sec per each imp./sec in the Ia afferents. 4. The Renshaw cells tested above responded also with increasing frequencies of discharge to increasing levels of static extension of the GS muscle. In particular the discharge frequency of Renshaw cells was on the average linearly related to muscle extension, at least for values ranging from 0 to 8 mm. The mean increase in discharge rate as a function of the static extension corresponded on the average to 0.89 imp./sec/mm. Since the discharge rate of the primary endings of muscle spindles recorded from the deefferented GS muscle increased by 2.62 imp./sec/mm, it appears that the mean increase in the discharge rate of Renshaw cells as a function of static extension corresponded to 0.34 imp./sec per each imp./sec in the Ia afferents.


The sensitivity of Renshaw cells to velocity of sinusoidal stretches of the triceps surae muscle. 1. The electrical activity of Renshaw cells monosynaptically excited by ventral root stimulation and disynaptically excited by electric stimulation of the group I afferents in the GS nerve has been recorded and their response to individual sinusoidal stretches of the deefferented GS muscle tested for different amplitudes and durations of the stimulus. 2. The experimental data indicate that the Rensahw cell responses are not only length dependent but also rate dependent. This finding indicates that the same Renshaw cells receive recurrent collaterals of both tonic and phasic motoneurons. 3. The observation that the discharge of Renshaw cells is particularly sensitive to the velocity of stretch suggests that the recurrent collaterals of large phasic motoneurons, which are recruited during high velocity stretches, exert a stronger excitatory action on Renshaw cells than do axon collaterals of the smaller tonic motoneurons, which are selectively stimulated during low velocity stretches.


A simple technique for thermal stimulation of single semicircular canals. Two simple thermodes for stimulating single semicircular canals have been designed in order to elicit eye nystagmus. The first, for warm stimulation, is based on the Joule effect: a silver needle is warmed up by means of a coiled nickrome wire. The temperature at the thermode tip is function of current intensity. The thermode for cold stimulation is a device in which a circulating freezing mixture cools a silver needle. The temperature at the thermode tip is proportional to the temperature of the freezing mixture.


Clinical and hormonal aspects in breast cancer with special reference to malignant evolutive push. It is tried to differentiate between various stages of malignant evolutive push and normal mammary tumors to establish an individual therapeutic procedure. Besides mammography and thermometry, investigations of urinary excretions of estrogenic and androgenic steriods are qualified for this purpose. Patients with malignant evolutive push showed an increased excretion of estrogens which reached its highest levels in patients suffering from inflammatory mammary carcinomas. The excretion of 17-ketosteroids shows a behaviour vice versa. Altogether mammary tumors with malignant evolutive push are characterized by a state of absolute and relative hyperestrogenity respectively. This phenomenon preferably depends on the clinical stage of the disease than on the age of the patients.


[Hormonal treatment of breast cancer from surgical point of view (author's transl)]. At present the best results in treating breast cancer of stage I and II appear to be achieved by surgery alone. As an alternative method preference should be given to the so-called classical radical mastectomy. Restriction or widening of operative management may be useful in some cases, but the indication is problematic. There is a high risk of applying appropriate procedures to inappropriate patients. In radical mastectomy the incidence of errors and complications comes within reasonable limits. On the contrary, in stage III additional treatment is well justified. At this stage, surgery alone gives poor results. The fate of stage III patients first of all depends on the presence or absence of metastases; therefore, preference should be given to systemic additional treatment, but on the basis of individualized tried measures. Polypragmasia and blind systemic treatment are to be avoided. The time schedule of such additional treatment are to be avoided. The time schedule of such additional treatment has to be established, by controlled clinical trials. From these considerations, the following requirements can be formulated: 1. improvement of the oncologic level 2. centralisation in oncologic treatment and diagnostics 3. enlargement of existing or creation of new facilities for bi-chemical and other testing, and for scientific investigation at the oneologic centers.


[Investigation on radiosensitizing and tumor inhibiting actions of the antioxidant MTDQ (6,6'-methylen-bis/2,2,4-trimethyl-1-1,2-dihydroquinolin) (author's transl)]. Unlike the hitherto known antioxidants, MTDQ is not a radiation protective-but a radiation sensitizing agent. According to autoradiographic findings accumulation of 14C-labelled MTDQ occurs in tumor tissue. The compound was found to be suitable in the combined treatment (MTDQ and 300 R x-ray therapy). In these instances tumor weight of solid Ehrlich- and Yoshida-tumors will be reduced even by doses ineffective as monotherapy. The MTDQ pretreatment of NKLy ascites tumorbearing rats raised survival rat by 60 to 90 per cent (controls 20%) and inhibited growth of solid Yoshida-tumors. No side-effects have been observed. In contrast to other antineoplastic agents MTDQ does not induce granulocytopenia.


[Clinical evaluation of Ftorafur (author's transl)]. The new soviet antimetabolite Ftorafur (N1-2'-Furanidyl-5-Fluorouracil, FFU) has been clinically evaluated in 18 selected patients with various solid tumours. Several of them had been treated before with other drugs. FFU was given to 8 patients as a monotherapy whereas 10 patients received the drug in combination with other therapeutic measures. A total response rate of 9/18 was seen. Three out of 8 patients treated with FFU alone have responded objectively. Due to its low toxicity FFU became a clinically interesting drug which is suitable for long-lasting administration. Its therapeutic activity is similar to that of 5-Fluorouracil. FFU is especially effective in carcinomas of the breast and the gastro-intestinal tract. It can be applied locally or safely be combined with other drugs or with irradiation.


Menstrual cycle phases and personality variables as related to response to erotic stimuli. The present research examined the relationship between menstrual cycle phases and response to erotic stimuli. Correlations between response to erotic stimuli and extraversion and neuroticism, as measured by the Eysenck Personality Inventory, were also investigated. Subjects were 60 university coeds who were shown explicitly erotic slides and asked to rate their sexual arousal while viewing these stimuli. Although significant effects were found for slides, no significant differences were noted amont women at different points in the menstrual cycle. Nonsignificant correlations were obtained between slide ratings and extraversion and neuroticism.


Age and perceived effects of erotica-pornography: a national sample study. In the spring of 1970, a national sample survey of 2486 adults (aged 20-80) was studied to ascertain U.S. public attitudes toward and experience with erotic materials. Twelve items measured whether or not those interviewed believed that looking at or reading sexual materials had certain effects on themselves or others. Initial description of the results revealed a considerable diversity of opinion. This report provides a multistage typology of those item responses, beginning with characterization of items as positive, neutral, or negative in effect. Striking age gradients were observed at each stage in the typology formation. At first glance, these results are hardly surprising, yet introduction of controls for level of education, gender, and reported previous levels of actual exposure to erotica did not appreciably change the age-graded response pattern. The last stage in the typology contained four levels and showed an attribute solely desirable and/or neutral effects to erotica. Those who expressed neutral and mixed (strongly positive and negative) views were somewhat older. The next age norms about explicit sexual materials took on a perception of no effects or a position of uncertainty. Finally, those who believed that pornography has largely or solely undesirable effects on its consumers were oldest. The replicability of the pattern suggests a specific order in the underlying process of change in values (historical and/or intraindividual).


Measurement of sexual arousal in male homosexuals: effects of instructions and stimulus modality. Erections were measured in 20 male homosexual subjects under three instructional conditions and within three stimulus modalities. The three conditions were arousal (e.g., imagine yourself involved and get aroused), suppression (e.g., imagine yourself involved bu suppress erection responses), and rearousal (e.g., imagine yourself involved and get aroused). The three stimulus modalities studied were video tapes, slides or pictures, and audio tapes of homosexual cues. The results show that video tape generates the highest level of arousal, audio tape the lowest level of arousal, and slides an intermediate level. Both video tape and slides show substantial voluntary suppression effects. During suppression, video tape continues to elicit relatively high levels of arousal in contrast to slides and audio tapes, which are equally low.


Rehabilitation professionals and sexual counseling for spinal cord injured adults. The Michigan Rehabilitation Association (M.R.A.) and the Program in Human Sexuality of the University of Minnesota collaborated to produce a 1-day seminar on sexual function in spinal cord injury. Evaluation of the participants and the seminar showed that the program was beneficial for most and harmful for few. Questionnaire responses indicated that few M.R.A. members are currently doing sexual counseling but many see an opportunity to do so. A relationship appeared between those who have received some form of training in sexual counseling and those who are doing counseling with clients. It is postulated that frank and sincere discussion of sexuality may improve rapport between client and counselor. However, before such an interaction can comfortably take place, the counselor may gain from an opportunity to examine his or her own attitudes toward human sexuality and gather more information about the sexuality of physically disabled adults.


A body image scale for evaluating transsexuals. Body image has come to mean not only the way one perceives his body but also how one feels about these perceptions. It is an important part of one's total self-concept. As such, it can present a significant problem for many individuals. For individuals with gender identity problems, such as transsexuals, body image dissatisfaction and distortion are a fundamental aspect of their condition. It is possible to more fully understand this condition by appreciating the distinction between the reality of the transsexual's body and his preferred body image. The Body Image (BI-I) scale presented here representa an effort to quantify the transsexual's body attitude. It consists of 30 body features which the subject is asked to rate on a 5-point scale of satisfaction. This test, as part of a larger seven-test battery, was administered to 16 male and 16 female transsexuals. The data have been analyzed for comparisons between males and females, for the effects of endocrinological and surgical treatment on body attitude, and for the common denominators which characterize the transsexual's body attitude. This instrument is being used as an additional tool in evaluating the transsexual's request for sex-reassignment surgery and in following those individuals who have been accepted for treatment as they progress through the evaluation and treatment program.


Sella turcica in male-to-female transsexuals. Roentgenological examination of the skull in 11 male-to-female transsexuals revealed considerable asymmetry (2.5-3 mm) of the sellar floor in three cases. There was no asymmetry exceeding 1.5 mm in 103 male controls. Asymmetry of the sella turcica suggests the presence of an intrasellar pituitary tumor. This finding in three patients with transsexualism is of interest in view of reports of endocrine disorders or hormonal secretion abnormalities in patients with atypical sexuality or gender identity problems.


Morphology, biochemical analysis and neuraminidase activity of rubella virus. A simple and reproducible method for the production of purified rubella virus is described. Purified virus was subjected to morphological and chemical analysis. The virus particles were rather pleomorphic (60 nm diameter), sometimes with one or more peripheral protrusions. The viral surface, revealed by negative staining, was composed of spikes 6 nm long, featuring enlarged ends. In SDS-urea-polyacrylamide gel electrophoresis, 4 major and 4 minor polypeptide bands were revealed. Total lipids and phospholipids were analysed on the same preparation. The viral particles were composed of RNA: 0.030 mg, and lipids: 0.245 mg, of which 0.169 mg were phospholipids for each mg of viral protein. Biologically, the purified virus preparation showed high infectivity, a high hemagglutination titre and a weak neuraminidase activity under defined conditions.


Estimation of hemagglutination-inhibition titers. In the hemagglutination-inhibition test, simple relationships exist between units of hemagglutinating virus and hemagglutination-inhibition antibody titers. Equations have worked out which allow estimating antibody titers for different virus doses, provided all other parameters are kept constant. They are applicable when the isofixation lines in log-log plots as obtained in box titrations either are positioned at angles of 45degree or deviate from this value. Using lower or higher doses of hemagglutinin in the test, the coefficient of variation of the estimated antibody titers was found to be approximately 4 per cent. This procedure is useful in a number of virus-cell-serum systems and allows comparisons of antibody titers obtained in different laboratories.


Structural polypeptides of California encephalitis virus: BFS-283. The polypepetides of California encephalitis virus (BFS-283) were analyzed by polyacrylamide gel electrophoresis (PAGE). Four polypeptides were detected in virions grown in both BHK-21 and LLC-MK2 cell cultures with molecular weights of 17,500. 30,000, 38,000, and 82,000 (VP-1, VP-2, VP-3, and VP-4, respectively). Viral proteins 2, 3, and 4 were glycoproteins and appeared to be associated with the envelope of the virus. Treatment of virions (rho=1.18 g/cm3) with then non-ionic detergent, NP-40, allowed detection of a RNA-rich fraction (rho=1.26/cm3) with contained the smallest polypeptides (VP-1).


A mouse hepatotropic variant of influenza virus. A hepatotropic variant of avian influenza virus A/Turkey/England 63 (Hav 1, Nav 3) was selected by serial passages in mouse liver. Adaptation to this organ was established after 13 in vivo passages and was found to improve during further passages as shown by increasing rates of replication in livers of ICR mice. The mutant virus finally selected was stable and differed from the original virus mainly in lethality upon intraperitoneal injection in mice, in its ability to grow to high titers in livers of susceptible animals and in plaque morphology in chick embryo fibroblasts. No differences were detected in hemagglutination inhibition and neutralization by standard mouse antisera. Pathogenicity for the liver was independent of the route of inoculation, included other laboratory animals sensitive to influenza virus and could be inhibited by amantadine. Fatal hepatitis in 50 per cent of susceptible mice by the intraperitoneal route required from 10 to 20 EID50-. Pathological changes consisted of severe necrosis of liver parenchyma accompanied by release of F antigen into the serum and were apparently due to virus replication in hepatic cells as evidenced by immunofluorescence. The main implications of this animal model for studies on experimental hepatitis and on myxovirus-host interactions in an organ not usually associated with influenza are discussed.


Abortive rabies in rabbits and white rats infected intracerebrally. Non-fatal rabies was successfully reproduced in rabbits infected intracerebrally with a highly pathogenic strain of street virus isolated from a man who had died of hydrophobia abter a dog bite and in white rats infected intracerebrally with the CVS strain of fixed virus. All the animals were pretreated with a sublethal intraperitoneal dose of live rabies virus. The surviving animals showed residual neurological symptoms (except one rat) in the form of paresis (both mild and marked) and high titres of virus-neutralizing antibody in the brain comparable to the level of serum antibody. Successful reproduction of abortive rabies in rabbits infected intracerebrally with the classical strain of street virus suggests that different forms of rabies infection may probably exist in nature.


Relation of virus particle counts to the hemagglutinating activity of influenza virus suspensions measured by the HA pattern test and by use of the photometric HCU method. The ratios of the number of virus (n.v.p.) to the hemagglutinating activity were determined for a series of influenza A and B strains using both the photometric HCU method and the HA pattern test. The logarithms of the ratios of n.v.p./hcu ranged from 7.06 to 7.54 and the logarithms of the ratios of n.v.p./HA from 6.87 to 7.56. While the n.v.p./HA ratios of different strains showed significant differences in a number of cases, such differences were not found for the n.v.p./HCU ratios with the only exception of the strain B/Hong Kong/8/73 differing uniformly from the other strains tested. Since the standard deviation of HCU values ranged from 0.006 to 0.039 log units and that of HA titers from 0.076 to 0.272 log units, it was concluded that the differences of n.v.p./HA ratios found were due to the range of variance of HA tests and did not reflect strain specific differences. The degree of purity of virus suspensions was found not to influence measurably the log n.v.p./HCU values.


[Effect on hepatocytes of the nuclear fraction of a liver homogenate]. The work presents the results of investigating the DNA synthesis in hepatic cell nuclei of mice as well as changes in the ultrastructure of hepatocytes nuclei of the rat after injections of nucleic fraction of the liver homogenate. The obtained data clearly suggest that reparation of the amount of DNA in the nuclei of hepatocytes of mice after a decrease of its amount due to the action of nucleic fraction results in increasing the number of hepatocytes synthesizing DNA. The comparison of the obtained results with the evidence of cytophotometry has shown that increased DNA synthesis is observed at that very time when the amount of DNA in hepatocytes nuclei began to increase. The electron microscopic investigations have confirmed the supposition of partial destruction of DNA in hepatocytes nuclei under Effects of nucleic fraction of the liver homogenate. The electron microscopic study evidences that in hepatocytes nucleic DNA is found in two different forms corresponding to two forms of chromatin--diffuse and condensed. The latter is characterized by lability to nucleic factors and readily undergoes destruction under their effects.


[Analysis of the mitotic activity of the lymphoid cells of the thymus in relation to age]. The mitotic activity of lymphoid cells of the thymus was studied separately in the subcapsule zone of the cortical substance, cortical substance and medullary substance of newborn, 21-day, 3-, 4-month and 12-month-old mice. In addition to counting mitoses (MA%) histograms of the organ lobes were drawn with exact localization of mitoses of dividing cells. The greatest index of mitotically dividing cells was noted in the subcapsule zone of newborns and 21-day-old mice (5,2+/-0,9 and 4,7+/-0,5). After sex maturation the mitotic activity considerably decreased but in 3-, 4- and 12-month-old mice, the mitotic coefficient of lymphoid cells also retained rather high level (2,6+/-0,3 and 2,1+/-0,2) though processes of involution took place in their thymus.


[Vascularization of tumors of the mammary glands]. The study of peculiarities of the blood supply of pre-tumour foci and cancer tumours of mammary glands of humans and mice of highly cancerous strains "A" and "C3H" by means of injectional, histological, histo- and enzymochemical and electron microscopical methods has shown that vascularization of corresponding zones alters with development of pre-cancerous growings in mammary glands. The most pronounced alterations are observed in the vessels of cancer tumours depending on the developmental stage, histological structure and differentiation degree. Changes in the character of "angioplastic" reaction, ultrastructural and histochemical reorganization of the vascular wall explain the peculiarities of microvascularization and metastazing of cancer.


[Prolonged hypokinesia and its influence on the tissues and vessels of the extremities in experiments]. The work describes the results of complex investigation of the state of the supporting-motor apparatus of extremities of dogs subjected to six-month-long restriction of motor activity and the following reparation during a month. Intravital rentgenological, anatomical, histochemical and electron microscopic methods were used. It was shown that continuous hypokinesia resulted in substantial alterations of the vascular bed in the macro-micro-ultrastructural level, disturbance of metabolism, focal reconstruction of tissues of the extremities by the type of natural death of ultrastructural elements without a following reparation. A one-month term appeared to be insufficient for reparation of structural disorders. Special attention was given to reactions of the vascular system. Signs of blood transport via extracapillary pathways from the arterial bed into the venous bed were noted.


[Structure and function of the microcirculatory bed in the preserved heart]. The morphological analysis of the state of the heart during hypertermal perfusion with different conservants reveals clear dependence of the microcirculation and the activity of the heart upon the type of the conservant. Perfusion with a salt solution and hemodilution is accompanied by pronounced disorders in microcirculation and unsatisfactory parameters of the cardiac activity. Conservation with cryoprecipitated plasma is characterized by comparatively less microcirculatory disorders, but fails to give a reliable safety of the heart. When using medium 199, changes in microcirculation were found to be minimal and parameters of cardiac activity were satisfactory. In the complex of non-specific changes in microcirculatory vessels the maximum structural lability was revealed in blood capillaries and vessels of the postcapillary-venular link.


[Viability of the kidney following autovenoplasty of its artery]. A segment of one of the renal arteries of the dog was substituted for a piece of the femoral vein of the same dog. Along the site of vascular anastomoses the kidney was excluded from general blood circulation. The results of the vessel plastics were not always favourable. Inspite of the independence of anastomoses in the course of operation, the lumen of the substituted piece of the renal artery underwent deformity in a number of experiments, the circulation of the kidney was disturbed, the parenchyma of the organ was injured, a part of renal bodies and tubules were atrophied, intraorganic vessels, especially glomeruli were reconstructed. The alterations were of focal character. In general the structure of the kidney was preserved. In most experiments the substitution of the renal artery for the own vein did not cause any disorders. The wall of the transplanted vein was soon reconstructed--artealized, the renal parenchyma kept normal structure. The success of vascular plastics and the full value of blood circulation was controlled by removing the twin organ. Animals with one kidney lived practically unlimited time without obvious disorders, the content of nitrogen in the blood was normal, no alterations were found in intraorganic vessels and the renal parenchyma.


[Comparative microspectrophotometric study of the activity of oxidative enzymes in separate types of fibers of the skeletal muscle of rats in the normal state and in experimental ischemia]. Microspectrophotometrical investigation of the activity of oxidative enzymes (glutamatdehydrogenase, cytoplasmic and mitochondrial alpha-glycerol phosphate dehydrogenase, succinic acid dehydrogenase and glucose-6-phosphatedehydrogenase) in certain types of muscular fibres of m. soleus, gastronemius and quadriceps of rats during experimental stenosins of the abdominal part of the aorta has shown the existence of certain cyclic changes in the enzymic activity of different periods after graded constriction which may be associated with arising of adaptational reactions of metabolic systems in striated muscles in response to chronic hypoxia.


[Cellular composition of the deep cervical and apical axillary lymph nodes in mature and aged humans]. Quantitative investigation of the cellular composition of follicles, cortical plato and myelinated strands of the regional lymphatic nodes in man has shown the lymphocytes (small, medium-size and large) to be prevailing cellular elements in all structural components of the node. Among them there are many small lymphocytes. In myelinated strands there are more reticular, plasma, mast cells and macrophages than in the cortical plato of the lymphatic node. The follicles of the lymphatic nodes are more homogeneous structural components. They consist mainly of lymphocytes. The cellular composition of profound cervical and apical axillary lymphatic nodes is different in the quantitative contact of cellular elements. It also changes depending on age and symmetry.


[Dynamics of changes in human cells with chromosome and genetic mutations in prolonged cultivation in a stationary phase. Report 1. Study of cells in xeroderma pigmentosum]. Ontogenetic changes of normal diploid cells and cells with genetic mutations (LHC-484 from a patient with xeroderma pigmentosum) have been studied under prolonged cultivation in a stationary phase. While investigating the dynamics of complex changes in certain cell properties and cell populations it was found that the cultivated human cells possess a particular pattern of ontogenetic changes for every culture and the dynamics of these changes depends upon the density of the cell population. Two cell subpopulations different in the degree of nucleus heterochromotinization have been discovered.


[Ultrastructure of the stria vascularis of the auricular labyrinth of the rabbit]. In the composition of the stria vascularis of the rabbit cochlea there are three types of cells: edging, medial and basal cells. The structure of these cells, their disposition and interrelationships within the stria vascularis are described. The nodes of the basal membrane whose ramification covers long mitichondria concentrating at the basement of edging cells are found in the structure of capillaries of the cochlea stria vascularis. It may be supposed that this powerful mitochondrial apparatus refers to the capillary system of the stria vascularis and represents a hypertrophic mitochondrial apparatus of pericytes. The capillaries of the stria vascularis are distributed mainly in longitudinal direction while the capillaries disposed transversely which are likely to be anastomoses were also found.


Potentiation by cocaine of relaxations of the guinea-pig colon caused by noradrenaline and by stimulation of adrenergic nerves. The distal colon of the guinea-pig is relaxed by noradrenaline, by isoprenaline and by the stimulation of fibres running with the colonic nerves or intramurally. The relaxations in response to stimulation of the colonic nerves have a guanethidine-sensitive (adrenergic) and a guanethidine-insensitive (non-adrenergic) component. Cocaine causes a three-fold sensitization of the muscle to noradrenaline but no sensitization to isoprenaline. Cocaine increases the duration, but does not affect the amplitude, of the relaxation observed when adrenergic nerves are stimulated, and affects neither duration nor amplitude of the non-adrenergic response. The adrenergic nerve terminals lie in Auerbach's plexus, not in the longitudinal muscle. It is concluded that the sensitization to noradrenaline and the increases in durations of responses to adrenergic nerve stimulation are due to inhibition of catecholamine uptake into adrenergic nerves by cocaine. It appears that, even where the neuromuscular separation is large as it is in the colon, the concentration of exogenous noradrenaline at the receptors can be decreased by neuronal uptake, and the uptake mechanism can modify responses to nerve stimulation in vitro.


Transfer functions for arterial oxygen saturation during +Gz stress. Discrete, finite, Fourier transforms of input +Gz stress and output arterial oxygen saturation (Sao2) were used to obtain transfer functions between G and Sao2 in 12 subjects. Ensemble averaging of transfer functions based on responses to variable G stress provided reasonable capability for predicting Sao2 responses to sustained 6-G stress. Prediction of responses to variable G stress from transfer functions based on responses to sustained G stress was unsuccessful, however. A synthetic transfer function with physiologic explicability and substantial predictive ability was obtained from an impulse response fabricated from simple mathematical functions.


Orthostatic responses in Caucasians and Bantu. Nine Caucasian and 13 Bantu young men, all untrained and unacclimated to heat, were tilted head-up for 20 min before and after 4 h of exercise performed at a load of 35 W at room temperature of 23 degrees C and in heat (33.9 degrees C DB, 32.2 degrees C WB). In heat, all Bantu but only four Caucasians completed the 4 h of exposure. The change in systolic blood pressure from recumbency to orthostasis was negligible in the Bantu and adverse in the Caucasians, during pre-exercise tilting at 23 degrees C. Similar differences were found during tilting after exercise at 23 degrees C. Post-exercise orthostatic heart rate did not differ between the two groups despite higher exercise heart rats of the Bantu. Seven subjects in each group fainted during heart-orthostatism, and the difference in systolic blood pressure between recumbency and orthostasis in heat was substantially more adverse in the Caucasians. High relationships were found between exercise heart rate, orthostatic heart rate, and fainting episodes. The results suggested that Bantu make better orthostatic adjestments than Caucasians.


Motion sickness questionnaire and field independence scores as predictors of success in naval aviation training. The present report has shown that a motion sickness questionnaire can be used to predict susceptibility to motion sickness or flight training success, depending on the items scored. There is a discussion of the theory that motion sickness results from conflicting perceptual inputs. This theory is related to aircraft operating conditions. Scores on a personality test which appear to be related to similar perceptual phenomena are related to aviation success. One phenotype, field independence, seems to be promising in this regard. In addition to use of this finding in aviator selection, it is felt that studies of this trait, as it relates to an ability to reconcile conflict and to motion sickness insusceptibility, should be conducted.


Effect of isolated head heating and cooling on sweating in man. A double climate chamber which permitted the independent regulation of temperature in each chamber was used to produce isolated head heating and cooling in three subjects. Deep body temperature was recorded from the tympanic membrane, oral cavity, esophagus, and rectum. Skin temperature was measured on nine body regions and a weighted mean skin temperature was calculated. Sweating rate was measured by resistance hygrometry from six regions. When head skin temperature was increased, deep body temperature measured at the tympanic membrane and oral cavity increased more than esophageal temperature, while rectal temperature remained essentially unchanged. Sweating rate increased when head skin temperature increased and again, somewhat later, as the tympanic membrane and oral temperatures began to rise. When head skin temperature was decreased, tympanic membrane and oral temperatures decreased and sweating again followed the changes in skin temperature as well as the changes in tympanic membrane and oral temperatures. Since it has been shown that head skin temperature is particularly important in determining thermal comfort and sweating rate when compared to other body regions, it is suggested that this particular sensitivity is in part due to a thermal counter-current exchange between venous blood draining the head and arterial blood ascending to intracranial thermoreceptors. Such an exchange would correspond to similar mechanisms present in other species.


Renal effects of continuous negative pressure breathing. Continuous negative pressure breathing (CNPB) was utilized to simulate the thoracic vascular distension of zero G or Space, in 11 anesthetized rats. The animals underwent renal clearance and micropuncture renal nephron studies before, during, and after CNPB. Four rats were pretreated with a high salt diet and I-M desoxycorticosterone (DOCA) in excess. None of these rats diuresed with CNPB. In contrast, five of the seven remaining rats increased the fraction of the filtered sodium excreted (CNa/GFR, p less than 0.05) and their urinary flow rate (V, p less than 0.05). Potassium excretion increased (UK V, p less than 0.05). End proximal tubular fluid specimen's TF/P inulin ratios were unchanged. Whole kidney and single nephron glomerular filtration rates fell 10%. CNPB, a mechanism for atrial distension, appears to cause in the rat a decrease in distal tubular sodium and water reabsorption. Exogenous mineral-corticoid prevents the diuresis, saluresis, and kaluresis. In a separate group of five rats, the CNPB was prolonged or excessive (CNPB greater than 3.5 cm H2O negative pressure); in these, the diuresis ceased and/or antidiuresis occurred. This confirmed the adequacy of other nonatrial volume control mechanisms in regulating renal salt and water conservation in opposition to the studied atrial-renal (Henry-Gauer) reflex of thoracic vascular distension. It encourages us to suggest that the atrial distension reflex diuresis that occurs with shifts of blood to the thorax in assuming a weightless condition, if comparable to the thoracic vascular distension of this model, will not progressively impair the circulation or the mammal but will be minor and short-lived.


Effects of mechanical vibration on rat plasma calcium, magnesium, phosphate, and xanthine oxidase. Sprague-Dawley rats were vibrated for 4 min in one of 12 combinations of G levels (+/-2, +/-4, or +/-8 GX) and frequency ranges (12-61, 62-111, 112-161, or 162-211 HZ). The animals were restrained and conscious during vibration. Plasma calcium, magnesium and inorganic phosphate concentrations as well as xanthine oxidase activities were determined for each animal at various times before and after vibration. Vibration at specific G levels induced physiological changes in plasma calcium, magnesium, and xanthine oxidase levels. Plasma inorganic phosphate concentrations appeared to increase with an increase in the displacement of vibration. All of the effects observed occurred within 24 h of vibration treatment. An effect of the frequency of vibration was not observed with any of the parameters examined. Factors involved in performing the experiments also were able to induce certain physiological changes, viz., the level of plasma calcium and xanthine oxidase activity.


Heart biochemical responses in miniature swine subjected to +Gz acceleration. Myocardial biochemical systems which are sensitive to hypoxic and ischemic insult were studied to determine the possible etiology of ventricular endocardial hemorrhage in miniature swine following +GZ stress. Unanesthetized animals were subjected to a single, 120-s +9 GZ acceleration. Approximately 1-2 h following +GZ exposure, the animals were anesthetized and the hearts removed for analyses. Acceleration exposure resulted in the loss of acid phosphatase enzyme activity from the membrane-bound lysosomal fraction with concomitant increased activity in the soluble fraction. This suggests that lysosomal membrane integrity had been disrupted. Mitochondrial preparations from +GZ-stressed hearts exhibited marked increases in active respiratory rate and rate of calcium transport while oxidative phosphorylation efficiency was unchanged. The results clearly indicate that +GZ acceleration is capable of altering myocardial biochemical systems. However, the results tend to suggest that these alterations in cellular processes may be mediated by influences other than hypoxia or ischemia.


Anthropometric sizing program for oral-nasal oxygen masks based on 1967 U.S. Air Force survey data. A new sizing program for oral-nasal masks, based on total facial length, has been developed through an analysis of the 1967 USAF anthropometric survey head and face data. A four-size series of three-dimensional face forms has been sculpted based on this sizing program as a design aid for sizing such masks. This report includes a discussion of the theoretical and practical aspects of the sizing analyses and procedures, and establishes design limits and procurement tariffs for the four sizes of masks. The MBU-12/P oxygen mask, an aoral-nasal pressure-demand type of mask, has been fabricated in accordance with this sizing system using the face forms as sizing guides. The results obtained during fit-tests using 66 USAF personnel as subjects are described. The authors concluded that the dimensional sizing of the oral-nasal oxygen mask facepieces is valid for USAF flight crews.


Laboratory assessment of the AN/PVS-5 night vision goggle. Laboratory assessment of the AN/PVS-5 Night Vision Goggle was conducted. Visual fields, goggle infrared source, useable range, and detectability of targets with the goggle were measured. Illumination levels of -8.37 and -9.17 log lm/cm2 were adequate for 90% detection of 0.14 and 0.07 acuity targets, respectively. Calculations of distances at which various surface and airborne targets subtended comparable visual angles and tables of natural brightness conditions are presented to permit translation of laboratory values into field conditions. While further field evaluation is anticipated, the laboratory assessment indicates that the goggle can significantly facilitate aircrew night visual performance.


Cardiac injuries in aircraft occupants resulting from aircraft accidents. The author reports that relatively frequent injuries to the thorax and to the heart are established in autopsies of aircraft fatalities. A review of 128 autopsy protocols of aircraft accident fatalities revealed 111 cases of severe contact injuries to the thorax and 98 cases of traumatic injuries to the pericardium and the heart. Accepting the fact that persons injured if traffic accidents display cardiac injuries in 25% of the cases, the number of traumatic heart lesions inflicted in persons in aircarft accidents is three times as high, a fact which may be attributed to the far higher speeds of the aircraft at the moment of impact with resultant forces of deceleration. Causes and mechanisms of the development of cardiac lesions as well as necessary recommendations for the improvement of the health protection of aircraft occupants are discussed.


Evaluation of possible microwave-induced lens changes in the United States Air Force. An Air Force examination team performed ophthalmologic examinations on 817 subjects in a double blind fashion. The subjects included 477 workers in the microwave radiation field and 340 control subjects with no known history of occupational exposure to microwave radiation. The intent of the study was to determine if a significant difference existed between the two groups for the presence of three lenticular findings equated with early cataract formation. No significant difference was found. Thus, this study does not support the contention that microwave exposure in the military environment is causing human cataracts at levels permitted by U.S. Safety Standards.


Testitis (excessive anxiety about flying checks). Excessive anxiety about flying checks--"testitis" or "checkitis"--is a relatively common cause of loss of licence by aircrew. This paper describes the syndromes seen in testitis and treatment which has resulted in alleviation of symptoms in nine out of 30 cases.


Heart rate monitoring of pilots during steep-gradient approaches. As part of a large scale investigation into noise abatement landing approaches, one trial involved the flight evaluation of steep-gradient and two-segment approaches; these were 3 degress, 6 degrees, 7.5 degrees, and 9 degrees single-segment, and 7.5 degrees/3 degrees two-segment approaches. To augment the subjective opinions of the test pilots, their heart rates were monitored during all the experimental runs. The resulting heart rate values for the different approaches correlated reasonably well with the subjective ratings of the relative workload levels. There is some evidence that the pilot workload level for the 7.5 degrees/3 degrees approaches is of the same order as the level for the conventional 3 degrees gradient.


Electromagnetic field effects in nerve tissue. In the present work, an attempt has been made to produce structural alterations in tissue from the nervous system of bullfrogs by means of a high-intensity electric field. The electric field used to expose the tissue was compased of a train of high-intensity, short-duration pulses. Theses pulses provide a high electric-field intensity in the tissue, yet a low enough absorbed-energy density to cause negligible thermal heating. Exposed and control tissue prepared for light microscope investigation was stained with thionin and hematoxylin and eosin stains. No gross histological alterations of the large motor neurons of the exposed tissue were found when compared with the control tissue.


Histological Studies in Hodgkin's disease. 200 cases of Hodgkin's disease were found in a revision of the lymph node biopsies studied between 1940 and 1973 at the Institute of Pathology of the Buenos Aires Medical School. Using Rye's nomenclature, 37 (18%) were classified as lymphocytic predominance, 60 (30%) as nodular sclerosis, 81 (41%) as mixed cellularity and 22 (11%) as lymphocyte depletion type of Hodgkin's disease. Preservation of various lymph node structures was observed in 54% of the 200 cases and was more common in the less aggressive varieties of Hodgkin's disease such as lymphocyte predominance and nodular sclerosis. The differences were statistically significant (P less than 001) for the preservation of the medullary sinus and capsule of the lymph node. The presence of sarcoid-like granulomas was more frequent in the lymphocyte predominance type and foam cell areas with Touton giant cells were seen only in cases of nodular sclerosing Hodgkin's disease. Vein invasion was present only in mixed cellularity and lymphocyte depletion hodgkin's disease.


Hormonal activity of testes in aged rats with leydig cell hyperplasia: histochemical investigation of some hydroxysteroid dehydrogenases. The following enzymes were employed in order to investigate the hormonal activity of the testes in aged rats: 3-beta hydroxysteroid-DH, 11-beta-hydroxysteroid-DH, and 17-beta-hydroxysteroid-DH. Our investigations show that in the non-altered testis of the aged rat the same enzyme activities can be observed as in young and sexually mature animals. A proliferation of the Leydig cells (L.c.), occurring in the aging rat, brings about an increased activity of the above-mentioned steroid-DHs. An augmented production of testosterone is quite probable.


Detection of aerosols in the respiratory tract. A fluorescence method for the detection of inhaled aerosols in the respiratory tract has been described. The most suitable fluorescence indicator for the histological examination was ethidium bromide.


Spherical aggregates of coxsackie B4 virus particles in mouse pancreas. A high titer culture of Coxsackie B4 virus was used to induce pancreatitis in newborn mice. In animals sacrificed 1 or 2 days after intraperitoneal inoculation, we observed cytonecrosis consistent with picornaviral infection as well as necrosis indicative of pancreatitis. In addition, we observed aggregates of particles which seem to be Coxsackie B4 virus particles, some arranged in the typical picornaviral crystalloid lattice formation and others arranged into spherical masses approximately 102 nm in diameter. Depending upon the depth and orientation of section through the spherical aggregates, the particles were arranged into two patterns which were readily distinguishable. When the plane of section was through the center of the sphere, 10 particles circularly arranged around a dense particle core were observed. When the sphere was cut tangentially, the particles were arranged in a zig-zag pattern so that there were two concentric layers of at least 6 particles per layer, with no central core. Both crystalloid and spherical aggregates were observed free within acinocyte cytoplasm, and within autophagic vacuoles, cytosegresomes, and fine granular bodies of acinocytes, and within phagocytic vacuoles of macrophages. We conclude that the spherical aggregates represent a distinct crystalloid form of Coxsackie B4 virus during its replicative cycle, which may eventually develop into the more typical picornaviral crystalloid lattice configuration and that the spherical aggregates are located in foci of viral synthesis. Marked pathogenicity of Coxsackie B4 virus in the newborn mouse pancreas should be considered a factor in the observations noted.


[Pathology in the U.S.A. A glut of pathologists, the role of the autopsy and the future of the "clinical pathology"]. This analysis deals with selected questions regarding the status of pathology in the United States. For a long time, the number of pathologists, both in practice and in training, had been deemed inadequate, but present trends indicate the existence of a considerable surplus of specialists in this discipline. The autopsy is still an important field of endeavor for the American pathologist even tbhough autopsy rates have drastically declined everywhere and the exact role of this procedure is being reevaluated. The concept of "clinical pathology" which seeks to encompass a whole conglomerate of heterogeneous disciplines and still dominates the practice of pathology in North America has come under attack; some observers plead for the total separation of laboratory medicine from pathology as well as for the systematic and intensive development of subspecialties within the field of pathology.


[Vitiliginous depigmentation, liver and splenic lesions and struma due to occupational contact with paratertiary butylphenol--a new systemic occupational disease]. In workers occupied with the production of paratertiary butylphenol, a hepatosplenopathy and a goiter with disorder of the synthesis of thyroid hormone have been observed for the first time besides the well-known vitiliginous depigmentation. It is supposed that paratertiary butylphenol has a systemic effect and causes lesions of various organic systems.


[Fatal skin epithelioma in a stomatologist professionally exposed to x-rays]. An epithelioma of the volar face of the right index caused the death of a stomatologist whose skin had been exposed to X-rays for many decades when keeping dental films in place. The casuistics of the clinical picture are dealt with, and arguments are given for its recognition as an occupational disease. The evaluated X-rays dose (the accumulated dose was approx. 2,100 rem, i.e. relatively low) and modern knowledge on radio-medicine are commented with regard to dose-effect relationship.


2,3-Oxidosqualene cyclase and cycloartenol-s-adenosylmethionine methyltransferase activities in vivo in the cotyledon and axis tissues of germinating pea seeds. Axis tissues, root and shoot, of germinating pea seedlings actively synthesize sterol from [2-14C]mevalonate during the first 3 days of germination. In addition to the intermediates of sterol synthesis, cycloartenol and 24-methylenecycloartanol, these tissues also form the triterpene beta-amyrin. The cyclase catalysing the formation of cycloartenol from oxidosqualene is about four times as active as that for beta-amyrin synthesis. 2. Sterol synthesis in the cotyledon is negligible, but cycloartenol and 24-methylenecycloartanol, as well as beta-amyrin, are synthesized there. Oxidosqualene cyclase activity in this tissue is 2.6 times as active for beta-amyrin synthesis as for cycloartenol synthesis. 3. Comparison of the relative amounts of 14C in cycloartenol and 24-methylenecycloartanol in the axis tissues and cotyledons of 3-day-old seedlings point to relatively active cycloartenol-S-adenosylmethionine methyltransferase systems in both axis tissues and a poorly active system in the cotyledon. 4. The role of beta-amyrin synthesis in the germinating pea seedling is discussed.


The effect of ethionine on ribonucleic acid synthesis in rat liver. 1. By 1h after administration of ethionine to the female rat the appearance of newly synthesized 18SrRNA in the cytoplasm is completely inhibited. This is not caused by inhibition of RNA synthesis, for the synthesis of the large ribosomal precursor RNA (45S) and of tRNA continues. Cleavage of 45S RNA to 32S RNA also occurs, but there was no evidence for the accumulation of mature or immature rRNA in the nucleus. 2. The effect of ethionine on the maturation of rRNA was not mimicked by an inhibitor of protein synthesis (cycloheximide) or an inhibitor of polyamine synthesis [methylglyoxal bis(guanylhydrazone)]. 3. Unlike the ethionine-induced inhibition of protein synthesis, this effect was not prevented by concurrent administration of inosine. A similar effect could be induced in HeLa cells by incubation for 1h in a medium lacking methionine. The ATP concentration in these cells was normal. From these two observations it was concluded that the effect of etionine on rRNA maturation is not caused by an ethionine-induced lack of ATP. It is suggested that ethionine, by lowering the hepatic concentration of S-adenosylmethionine, prevents methylation of the ribosomal precursor. The methylation is essential for the correct maturation of the molecule; without methylation complete degradation occurs.


Differential subnuclear distribution of polyadenylate-rich ribonuclei acid during induction of egg-yolk protein synthesis in male Xenopus liver by oestradiol-17 beta. A 4-8-fold increase in the rate of hepatic nuclear RNA synthesis occurred within 11 h after a single injection of oestradiol-17 beta to male Xenopus to induce egg-yolk protein synthesis. 2. By using a gentle procedure for fractionating nuclei into their major structurally different components [J. R. Tata& B. Baker (1974) Exp. Cell Res. 83. 111-124], it was found that the hormone-induced increase in the total amount of newly made RNA was associated with a 2-10-fold increase in the poly(A) content of nuclear RNA. 3. When the poly (A) content of nuclear RNA was determined by hybridization to poly[3H](U) or specific binding to oligo(dT)-cellulose, most of the increase (10-fold) in poly (A) content of newly synthesized RNA was associated with the euchromatin fractions, whereas the increase was less marked in the other subnuclear fractions. 4. Resolution of nuclear RNA into poly (A)-poor and poly(A)-rich RNA species by chromatography on oligo(dT)-cellulose, followed by polyacrylamide-gel electrophoresis with sodium dodecyl sulphate or in the pressence of 99% formamide, revealed that the hormone caused a preferential enhancement of high-molecular-weight (25S-60S) poly (A)-rich HnRNA (heterogeneous nuclear RNA,) much of which was associated with euchromatin and not with the nuclear sap. 5. Induction of vitellogenin in male frogs was in particular characterized by the appearance of a high-molecular-weight polyadenylated component exhibiting a peak at 35-36S, i.e. a molecular weight of approx. 2.05x10(6)+/-0.15x10(6). Although there is no evidence as yet that such a polyadenylated high-molecular-weight nuclear RNA species contains sequences corresponding to vitellogenin mRNA, it is possible that a high proportion of the most stable form of the putative nuclear precursor to vitellogenin mRNA induced by oestrogen in male Xenopus liver may be only marginally bigger than the cytoplasmic mRNA, and may at any one time be predominantly associated with the euchromatin fraction.


Amino acid biosynthesis in mixed rumen cultures. Mixed rumen micro-organisms, maintained in continuous culture readily incorporated labelled HCO3- and acetate into amino acids. Labelled propionate, in contrast, was utilized only for isoleucine biosynthesis, but failed to label other amino acids to any significant extent. Evidence was obtained showing that in these mixed, i.e. symbiotic, cultures foward tricarboxylic acid-cycle reactions only proceed to 2-oxoglutarate. 14C distribution in amino acids clearly shows that 2-oxoglutarate is not oxidized further by tricarboxylic acid-cycle enzymes. Instead, acetate is carboxylated to pyruvate which is then carboxylated to oxaloacetate. Oxaloacetate equilibrates with fumarate and thereby carbon atoms 1 and 4 as well as carbon atoms 2 and 3 are randomized. Evidence was also obtained for the carboxylation of propionate to 2-oxobutyrate, isovalerate to 4-methyl-2-oxopentanoate, phenylacetate and hydroxyphentlacetate to the corresponding phenyl- and hydroxyphenyl-pyruvic acids and succinate to 2-oxoglutarate. Of the amino acid precursors investigated, only 3-hydroxypyruvate, the precursor of serine, appeared to be synthesized via an oxidative step, i.e. 3-phosphoglyceric acid to 3-phosphohydroxypyruvic acid. Most 2-oxo precursors of amino acids in these organisms appear to be formed via reductive carboxylation of the precursor acid.


Stimulation of hepatic mitochondrial calcium transport by elevated plasma insulin concentrations. The effect of insulin (injected intraperitoneally) on the transport of Ca2+ by hepatic mitochondria from rats was investigated. 2. Elevated concentrations of plasma insulin within the physiological range (10-100muunits/ml) stimulate the initial rate of Ca2+ transport into mitochondria at 4 degrees C by about 75% and prolong by approx. tenfold the time for which the mitochondria retain the accumulated Ca2+. 3. The prolonged retention of Ca2+ is observed under the conditions where hypoglycaemia is significantly decreased by the simultaneous injection of glucose and insulin. 4. A good correlation is observed between the effects on Ca2+ transport and the decrease in blood glucose concentration when the amount of insulin injected was varied. 5. The effects of insulin on mitochondrial Ca2+ transport are apparent at about 30 min after the injection, and are inhibited by cycloheximide. 6. There is little change in mitochondrial energy transduction after the administration of insulin. 7. The results are briefly discussed in relation to the mechanisms of Ca2+ transport across the inner mitochondrial membrane and the role of mitochondria in modifying intracellular Ca2+ concentrations with reference to the mechanism(s) by which insulin affects cellular metabolism.


Stimulation of protein synthesis in cultured heart muscle cells by glucose. Glucose stimulated the rate of incorporation of [3H]leucine into HCLO4-insoluble fraction of cultured rat heart muscle cells under both aerobic and anaerobic conditions. In the aerobic system the incorporation proceeded at a constant rate during 3h of incubation with and without glucose whereas in the anaeorbic system the incorporation ceased after approx. 60 min and could be renewed only by the addition of glucose. No correlation was found to exist between the above effect of glucose on protein synthesis and glucose-dependent changes in the intracellular ATP concentration. The extent of the stimulation of protein synthesis was related to the concentration of glucose. The effect of glucose was suppressed by cycloheximide but was not affected by actinomycin D. Glucose had no effect on the rate of transport of alpha-aminoisobutyric acid. Mannose also stimulated [3H]leucine incorporation. Substances that did not produce lactate were ineffective. Iodoacetate inhibited the stimulatory effect of glucose, but pyruvate, which by itself had no apprecialbe stimulatory action, relieved the inhibition induced by iodoacetate. There was no concomitant change in the concentration of ATP when iodoacetate inhibition was reversed by pyruvate. L-Lactate or other intermediates of energy metabolism could not relieve the inhibitory effect of iodoacetate.