Sexual variations in thermoregulation during heat stress.

Four male and three female physically fit, but untrained subjects performed a treadmill walking task in neutral (25 degrees C), warm (32 degrees C) and hot (40 degrees C) environments. The treadmill grade for each subject was based on 50% VO2 max as determined in a neutral environment. Environmental exposures were 2 h in duration divided into 40 min of rest, work, and recovery. No distinct sexual differences in rectal and skin temperature responses were observed in the three environments. The male subjects had higher heart rates and greater evaporative weight losses during exercise in all environments. The female subjects experienced less severe increases in metabolic requirements during work in the warm and hot environments than the male subjects. The greater percentage of increase in heart rates relative to changes in the metabolic cost of work in the females suggested a greater cardiovascular component of thermal regulation in the female than in the male subjects. The results of this study suggest that physically fit females are capable of working in the heat about as well as males when work load is relative to individual maximal aerobic capacity.


Disseminated intravascular coagulation developed in hyperbaric oxygen.

Male rats of 260 g were exposed to hyperbaric conditions of oxygen with different partial pressures and the changes of the haemostasis were studied. In 100% oxygen at 2 ATA, the animals died within 48 h. In 100% oxygen at 1 ATA, death occurred only after 3 d; however, in 24-48 h there developed disseminated intravascular coagulation (DIC). At the same time uncompensated acidosis of 7.34 +/- 0.02 was measured. Perivascular bleeding could be histologically demonstrated in different organs. The mixture of 60% oxygen and 40% nitrogen caused only a minimal DIC while a mixture of 40% oxygen and 60% nitrogen caused no changes in the haemostasis. Volunteer young males exposed to the mixture of 60% oxygen and 40% nitrogen, developed the beginning symptoms of DIC, which made it necessary to stop the experiments.


Stress in air traffic personnel: low-density towers and flight service stations.

Stress and anxiety levels were measured in 10 air traffic control specialists (ATCS) at two low traffic-density towers in Fayetteville (FYV), Ar, and Roswell (ROW), NM, and in 24 flight service (FS) specialists at those airports and at Okalhoma City (OKC), Ok. Physiological measurements consisted of heart rate and urine biochemical analysis  for 17-ketogenic steroids, epinephrine, and norepinephrine. On-duty arousal in ATCSs and FS specialists was evident both physiologically and psychologically; such arousal was within psychologically normal limits and was generally low physiologically compared to other air traffic control (ATC) facilities studied in the past. Physiological stress levels at these low-density towers and flight service stations were also low compared to other ATC facilities studied previously. Therefore, it is inappropriate to describe all air traffic control work, as is commonly done in the popular press, as unusually stressful. Such accounts in the popular press tend to deal with the exceptional, rather than with the typical, controller or facility.


Method for rehabilitation of the alcohol-addicted pilot in a commercial airline.

Based upon data available from the National Council on Alcoholism and encouraged by the emerging concept of alcoholism as a disease responsive to the multidisciplinary approach to its management, a program to assist alcoholic employees was instituted in 1968 at the United Airlines Maintenance Operations Center in San Francisco. This program was developed through the tripartite efforts of management, union and the medical department. Using this basic model, a similar effort to assist flight crew members of our San Francisco pilot domicile emerged in 1970. The method is oriented to the three-fold process of identification, referral for treatment, and followup. The mechanism of identification includes an intervention process. Treatment is accomplished in a specialty hospital embracing the principles of Alcoholics Anonymous. The essential monthly followup is continued for 2 years. Twenty-five pilots in United's system have been returned to flight deck duties after treatment and recertification.


Ten-year experience with abnormal EEGs in asymptomatic adult males.

This study reports a 10-year experience of the USAF School of Aerospace Medicine with spike waves of focal spikes on a screening electroencephalogram in aviators who did not have a history of seizure, unexplained loss of consciousness, or significant neurologic abnormality at the time of the first abnormal electroencephalogram. Only one of 20 patients went on to develop a seizure disorder 4 years after his first abnormal electroencephalogram.


Heterophoria--its influence on stereopsis and the importance of cycloplegia in refraction testing of pilot applicants.

Heterophoria, its influence on stereopsis, and the importance of cycloplegia in refraction testing of pilot applicants were studied. Distant heterophoria was found in 94.5-100% while near heterophoria was found in 86.9-98.1% of the cases, depending on the test used. Hyperphoria of over 1 prism diopter was extremely rare. No statistically significant correlation between distant heterophoria and the degree of stereopsis could be demonstrated at a range of up to at least 6 prism diopters. Cycloplegia induced a mean difference of +0.75 diopter in refraction before and during cycloplegia. Eight percent of the applicants failed because of refractive errors (spherical extremes, -0.75 diopter and +4.50 diopters; cylindrical extreme, 1.25 diopters). It is concluded that stereopsis does not seem to be affected much by heterophoria within moderate limits, and that cycloplegia in refraction testing of young pilot applicants must be considered relatively important.


Preventive effect of a vasodilator on the occurrence of decompression sickness in rabbits.

The effect of terbutaline on the occurrence of decompression sickness was studied in seven rabbits. Terbutaline is a vasodilator, a sympathomimetic beta2-receptor stimulator. The rabbits were given a hyperbaric exposition at 2 ATA followed by oxygen breathing at 1 ATA and a hypobaric exposition at 0.2 ATA. Each rabbit got a hyperbaric exposition long enough for symptoms of decompression sickness to occur at the hypobaric exposition. With a time interval of at least 1 week, each rabbit received an identical pressure exposition, except that terbutaline was injected intravenously at the beginning of the denitrogenation period at 1 ATA. Of the seven experiments with the drug, only one case of decompression sickness occurred and with a delayed appearance. This may be compared to rapid-appearing decompression sickness in all cases in the control series. The results may be of importance in diving routines and, possibly, in the treatment of decompression sickness.


Physiological and psychological effects of heat stress simulating cockpit conditions.

It is generally accepted that physiologically tolerable heat stress can adversely affect human performance, but it is difficult to predict the impact of a specific environment. Experiments were designed to determine the effects of thermal conditions similar to those occurring in aircraft cockpits in warm climates, where both high air temperatures and radiant heat play important roles. Subjects (n = 13) were exposed to heat for 2 h, had a 30-min break, then repeated the exposure. Conditions were Tdb = 35 degrees C and Twhb = 26 degrees C, with or without use of infrared lamps which raised globe temperature to 47 degrees C. Measurements included skin, rectal, and esophageal temperatures, heart rate, weight loss, and hematocrit. Subjective Fatigue Estimates (SFE) and Repetitive Psychometric Measures (RPM) were performed before, during, and after each heat stress. Both thermal conditions were physiologically compensable but induced marked subjective fatigue and altered the learning curve for some subtests of the RPM. Similar conditions in aircraft can be associated with impaired performance, particularly in new or emergency situations.


Effect of gravitational and inertial forces on vertical distribution of pulmonary blood flow.

Vertical distribution of pulmonary blood flow (VDPBF) was studied, using radioactive microsphere emboli, in dogs without thoracotomy in the right decubitus position during exposure to lateral (--Gy) accelerations of 1, 2, 4, and 6 G. At all levels of force environment studied, an inverse linear relationship was observed between vertical height in the thorax and pulmonary blood flow (ml/min/ml lung tissue) with a decrease in flow to the most dependent region of the lung despite large increases in intravascular pressures at this site. Changes in blood flow were smallest at the mid-lung level, the hydrostatic "balance point" for vascular and pleural pressures. These force environment-dependent changes in VDPBF are not readily explainable by the Starling resistor analog. Gravity-dependent regional differences in pleural and associated interstitial pressures, plus possible changes in vascular tone resulting from inadequate aeration of blood in the most dependent regions of the lung, probably also affect VDPBF.


Peritoneal lavage cooling in an anesthetized dog heatstroke model.

This study was undertaken to compare cooling in room air (27 degrees C, 20% RH), ice slush surface cooling, and peritoneal lavage cooling (6-10 degrees C) as methods for lowering body temperature in an anesthetized dog heatstroke model. We anesthetized 19 animals with sodium pentobarbital (25 mg/kg) intravenously, and maintained them in an ambient temperature of 42-46 degrees C with a water heating blanket approximately 2.0 h until rectal temperatures rose to 43.2 +/- 0.2 degrees C. At the maximum rectal temperature, the heating blankets were removed, and animals were cooled, observed until death occurred or 18 h elapsed, and then sacrificed. The data demonstrate that maximum cooling rates of rectal temperature were: peritoneal lavage, 0.56 degrees C/min; ice slush, 0.11 degrees C/min; and 27 degrees C air cooling, 0.06 degrees C/min. The incidence of 18-h survival for lavage-cooled dogs when supported with normothermic dialysis every 4 h was significantly greater than for either ice slush or air cooled dogs.


Hypoxia, smoking history, and exercise.

Six nonsmokers and six cigarette smokers, 22-34 years old, performed bicycle work (53% sea level VO2 max) for 30 min in an altitude chamber under four conditions: SL, simulated sea level (PIO2 = 159 torr, PB = 523 torr) with 0.5% HbCO; SLCO, simulated sea level with 4.2% HbCO; and ACO, altitude with 4.2% HbCO. During work at altitude, heart rate (HR), minute ventilation and tidal volume increased and diastolic blood pressures decreased relative to SL. Cardiac output (Qc), stroke volume (SV), and arterial-mixed venous oxygen difference (a--vO2) were similar in smokers and nonsmokers at SL, SLCO, and A. At ACO, nonsmokers increased Qc and SV and decreased a--vO2, but these were not influenced in the smokers. Smokers showed a graded increase in HR when exposed to work in SLCO, A, and ACO. Their lower finger temperatures during A and ACO suggested vasoconstriction in the extremities. Cigarette smokers may be partially adapted to hypoxia.


Time course of change in soleus muscle fibers of rats subjected to chronic centrifugation.

Soleus muscles from three groups of rats were analysed for changes in muscle fiber populations and diameters after being subjected to chronic centrifugation. The experimental groups were: earth control, raised at earth gravity with no rotation; rotation control, subjected to a gravitational force of 1.03 g and 30 rpm; and rotation experimental, subjected to a gravitational force of 2 g and 30 rpm. One male and one female of each group were killed at 7, 14, 21, 35, 42, 45, 49, 56 and 60 d after initiation of the experiment. Hypergravity resulted in an increase in the proportion of slow oxidative fibers. The time course of change in their muscle fiber populations is plotted. The time course of change in the ratio of body weight to muscle fiber diameter in the rotation control animals differed from that of the earth control and rotation experimental animals.


Some influences of touch and pressure cues on human spatial orientation.

During constant velocity rotation about his recumbent Z axis, a blindfolded subject feels as if he were on an orbital path in the same direction. This experienced motion results from the pattern of touch and pressure stimulation of the body surface. If the subject changes the pressure pattern on his body by bracing himself in the rotating apparatus in different ways, it is possible for him to influence profoundly and systematically his apparent orientation. For example, pressure on the top of his head while he is rotating can make the subject feel he is upside down on a cylindrical path. The changes in apparent ongoing posture elicited by different patterns of pressure cues are very similar for different subjects and are constant for the same subject over time. During experienced orbital motion, a subject will hear a continuously emitting sound source--one that is stationary in the external environment--as circling his head in the direction opposite that of his true rotation. If the rotating subject is permitted unrestricted sight of his surroundings, he neither experiences orbital motion nor mislocalizes sounds. These observations provide insight into the spatial orientation mechanisms that normally allow an organism to distinguish accurately between those changes in activity at its receptors contingent on its own movements, and those resulting from movement within the environment. They also provide a way of understanding some of the postural illusions experienced during exposure to unusual force environments, including free fall.


Prevention of acute paraquat toxicity in rats by superoxide dismutase.

Paraquat is a widely used herbicide which causes lung injury in man characterized by progressive parenchymal damage that may lead to fatal respiratory failure. The precise mechanism of injury is unknown but is related to the cyclic oxidation and reduction of paraquat in cells with resultant production of free radicals of oxygen. In this study, superoxide dismutase (SOD), an enzyme that catalyzes the dismutations of superoxide free radical (O2-) to less toxic forms, plus reduced glutathione (GSH), and d-propranolol (PROP), were evaluated for their ability to protect against acute paraquat toxicity. Rats maintained at room air were given 50 mg paraquat dichloride/kg body weight in a single intraperitoneal (IP) injection 60 min prior to receiving either 0.2, 2, 10, or 20 mg/kg/d SOD, 3.6, 7.2, or 14.4 mmol/kg/d GSH, 2 or 20 mg/kg/d PROP, or an equal volume of normal saline (controls) LP. in divided doses for 3 d. SOD significantly prolonged and increased survival at doses of 2, 10, or 20 mg/kg/d (p less than 0.05). In addition, histologic lung morphology in SOD-treated rats showed only minimal intra-alveolar hemorrhage and hypercellularity 24, 48, and 168 h after paraquat challenge. Treatment with GSH, PROP or 0.2 mg/kg/d SOD was not protective. Duration of survival, percent survival, and lung morphology in these groups were not significantly different from controls. These results indicate that a) SOD protects against the development of acute paraquat toxicity in rats, b) one mechanism of paraquat poisoning is increased biologic production of O2-, and c) SOD may have a role in the therapy of paraquat poisoning in man.


Inflight measurement of pilot workload: a panel discussion.

A group of U.S. scientists engaged in inflight measurements of pilot workload discussed the problems and aspects of workload; the techniques used for inflight measurements; the various workload models, such as design-oriented, operational, psychological, and physiological concepts; different experimental approaches; and experiences, results and further plans, during the 48th Annual Scientific Meeting of the Aerospace Medical Association in Las Vegas, Nv, on May 10, 1977. The contributions by the chairman and the five panel members are summarized.


Permanent changes in the spines of military parachutists.

To investigate whether parachuting causes permanent changes in the spine, 50 military parachutists (mean number of jumps 490 per parachutist) and 50 matched controls were studied. In X-rays of parachutists and controls, the frequency of degenerative changes differed in the cervical spine (46 and 20%; p less than 0.01), and in the thoracic spine (62 and 28%; p less than 0.05) but not in the lumbar spine (44 to 36%; not significant). Parachutists suffered significantly more often from stiff neck, but the incidence of other neck and back symptoms was the same in the two groups. The increased frequency of degenerative changes in the spine in military parachutists is probably due to repeated traumata which parachutists sustain on landing and, possibly, during the training period before parachute jumps.


Case report of an obsessive-compulsive personality: a precurser to accident proneness.

The social/physiological/psychological review of an aircraft accident involving input of incorrect controls and low-altitude ejection of a student naval aviator enlightened the investigators as to maybe a not-so-uncommon problem--accident proneness resulting from an obsessive-compulsive nonpsychotic personality. Review of the pilot's history reflected a perfectionist attitude since childhood with continuous associated near-serious accidents. Flight training revealed occurrences of over-correction, channelized attention, and denial of errors. With the demands of Naval Aviation that spurs the growth of the perfectionist, normal/abnormal parameters of obsession-compulsion as they present themselves must be cautiously examined.


Investigation of arterial bloodgases at altitude using constant-flow oxygen masks.

Arterial blood oxygen tensions up to 6700 m altitude (FL220) were measured polarographically while subjects breathed from various masks with constant-flow oxygen. The Sierra and Aro masks used for emergency decompression descent in commercial passenger aircraft, gave mean PaO2's of 130 +/- 7.6 and 130 +/- 12.1 torr at 6700 m (FL220) and 90 +/- 3.8 and 77 +/- 3.35 torr at 4260 m (FL140), respectively, when supplied with oxygen flows corresponding to those available in the Boeing 747. These oxygen tensions during descent are acceptable for normal physiological function in a heterogeneous population of air travellers whereas breathing ambient air during return to base at 4260 m (FL 140) (PaO2 of 48 or less) is not acceptable. The valveless Hudson 1007 and Puritan 114011 masks, used for air ambulance service, gave mean PaO2's of 110 +/- 2.7 and 98 +/- 4.5 torr at 6700 m and 80 +/- 3.0 and 77 +/- 2.5 torr at 4260 m under the same condition--significantly less than the Sierra mask.


Ca2+-uptake and -release phenomena from cardiac mitochondria under normal and ischemic conditions.

Guinea-pig and dog heart mitochondria were isolated in a KEA-medium. Ca2+-transport across mitochondrial membranes was measured continuously with an Aminco Dual-Wavelength-Spectrophotometer and murexide as a Ca2+-sensitive indicator. Ischemia was produced by cardioplegia at 15 degrees C according to Bretschneider. Guinea-pig heart mitochondria as well as mitochondria from dog heart show a spontaneous Ca2+-release without nonphysiological influence. Addition of 3.5 M Na+ can induce a very quick release of Ca2+ taken up by heart mitochondria. This release is different from that occurring spontaneously. Progressive ischemia results in a marked depression of Ca2+-uptake and spontaneous Ca2+-release.


Prevention of myocardial depression in experimental hemorrhagic shock by pretreatment with hydrocortisone.

The left anterior descending or left circumflex coronary artery was cannulated in ten dogs. 4 mg/kg hydrocortisone were slowly infused and the cannula was withdrawn. The dogs were then subjected to hemorrhagic shock for 90 minutes followed by retransfusion. The contractile force (CF) and its first derivative (df/dt) were measured in the pretreated (infused) area and in a control (non-perfused) area of the left ventricle. During the shock period, CF and df/dt in the non-pretreated area showed a 50% reduction in comparison to the pre-shock level, whereas the contractile force in the area that had been pretreated with hydrocortisone did not change when compared to the pre-shock period. This study shows that myocardial depression secondary to hemorrhagic shock can be effectively prevented by pretreatment with hydrocortisone.


Why does the cardiac force-velocity relationship not follow a Hill hyperbola? Possible implications of feedback loops involved in cardiac excitation-contraction coupling.

1. If cardiac force-velocity (PV) relationships are determined in a rhythmically beating isolated preparation by progressively changing afterloads, the PV curves obtained exhibit a characteristic nonhyperbolic shape with an upward convexity in the force domain close to P0. It was suggested by others that this might be due to contractile element (CE) shortening against series elastic component (SEC) and/or the early decay of the active state at isometric peak tension. 2. The present investigation performed in isolated cat papillary muscles demonstrates that neither CE shortening against SEC nor the variation of the intensity of the active state can fully account for the nonhyperbolic shape of cardiac PV curves. 3. On the other hand large parts of the remaining deviation could be eliminated if the "progressive loading sequence" (PLS) was replaced for an "interpolated loading sequence" (ILS). Here, the muscle contracts under steady state conditions either isometrically or isotonically (zero load). Single afterloaded test contractions are interpolated after every 10th beat. 4. It is concluded that the nonhyperbolic shape of cardiac PV curves, determined by progressively changing afterloads, is the expression of at least four factors: (i) the existence of displacement dependent variation of excitation-contraction coupling (including the contraction-excitation-contraction recoupling loop), (ii) CE shortening against non CE bound SEC, (iii) a variable active state and (iiii) a fourth unknown mechanism.


Influence of drugs on the relationship between sinus node recovery time and calculated sinoatrial conduction time in man.

Sinus node recovery time (SRT), the pacing rate with the maximal SRT, and calculated sinoatrial conduction time (SACT) were studied by overdrive atrial pacing and programmed premature atrial stimulation in 78 patients before and after the application of several antiarrhythmic drugs or of atropine. The maximum SRT was usually observed at lower rates of atrial pacing after application of a drug that prolonged SACT, whereas the opposite behaviour was observed in the majority of cases in whom the drug tested shortened calculated SACT. However, this relationship was not observed in all cases which may be due to random changes of sinus node automaticity or sinoatrial conduction, or to the inability of programmed premature atrial stimulation to detect changes of SACT. The results of this study further substantiate the importance of the properties of sinoat;ial conduction for achieving a maximal depression sinus node activity during high rate atrial pacing.


[Coronary risk factors and social class. Screening in employees of a large industrial firm (author's transl)].

In Munich, 1477 employees (868 males and 609 females) of a large industrial firm were examined with regard to coronary heart disease risk factors. The known risk factors--overweight, disorders of the lipometabolism, diabetes, cigarette smoking, hypertension, pathologic ECG, physical inactivity--as well as certain somatic complaints and mental stress were checked for their distribution within the various social levels. With the exception of cigarette smoking among women and professional worries among men, in both sexes the members of the upper social group are less burdened with danger factors than the average. Aside from high blood pressure and disorders of the lipometabolism, which predominate in males in the middle layers, and cigarette smoking, which prevails among females in the upper social group, the risk factors pile up in the lowest social level. Our results will be discussed and compared with other studies.


Intropic and electrophysiological action of humoral factors released in cardiogenic shock after acute myocardial infarction.

The inotropic and electrophysiological effects of plasma obtained from patients and experimental dogs during cardiogenic shock following acute myocardial infarction were studied. Changes in the isometric contraction and the intracellular action potential were determined in isolated papillary muscles of rabbits. Control plasma collected from normal subjects produced no significant changes in the contraction or the electrical parameters. Plasma from shock patients decreased peak force by 42% and the maximum rate of force development by 38% in comparison to control values; the time to peak of contraction, the relaxation time and the action potential parameters were not significantly altered. Corresponding results were obtained with plasma from dogs before and during experimental cardiogenic shock. Biochemical determinations failed to identify a single specific "myocardial depressant factor" in the plasma of patients and dogs with cardiogenic shock. The results suggest that (1) various humoral factors released during cardiogenic shock may depress the contractile function of cardiac muscle and (2) that the observed negative intropic effect is not due to electrical changes in the cell membrane.


X-ray microanalysis of isolated perfused rat hearts.

X-ray microanalysis was carried out on sections from isolated hearts perfused with a modified Krebs-Henseleit solution with or without isoproterenol. Changes in P, Ca and Zn concentrations could be detected after isoproterenol and some correlation with hemodynamic and morphological parameters was observed. Ratios between P/Ca in myonuclei and the ratios of interstitial cell to myofiber nucleus calcium were related directly to the state of the heart.


A biometrical approach for determining the effects of treatment with a chemotherapeutic agent upon heart weight in the mature rabbit.

Changes in heart weight as attributable to treatments involving a chemotherapeutic agent (CTA) were studied using adult rabbits. CTA was administered to each subject three times a week until sacrifice. Dose level per administration was held constant with respect to mg of CTA per kgm of body weight. The level of treatment for a given animals was then determined by the length of time the animal was in the treatment program prior to sacrifice. At sacrifice, variations in heart weight were evaluated relative to sex, initial body weight, relative change in body weight and level of treatment. Regression techniques were used in the analysis of data. This procedures allowed for differentiation between the direct effects and indirect effects of treatment. The direct effect was shown to cause a significant increment in heart weight. The indirect effect as related to loss body weight was shown to lead to a significant decrement in heart weight.


The heterogeneity of the lipoprotein lipase of rat epididymal adipose tissue.

Lipoprotein lipase is heterogeneous, and it was suggested that the enzyme in adipose tissue is transformed from a species of mol. wt. approx. 120000 to forms of much higher molecular weight as it is secreted from the fat-cell. This paper demonstrates that the forms of higher molecular weight are probably artifacts. Enzyme preparations were characterized by gel filtration, by density-gradient centrifugation and by affinity chromatography. The results indicate that the enzyme forms of mol. wt. greater than 120000 result from an association of the enzyme with particulate material. It is therefore necessary to reconsider schemes that have recently been proposed for the synthesis and export of lipoprotein lipase.


Incorporation and release of inorganic phosphate in horse spleen ferritin.

When ferritin is reconstituted from Fe and apoferritin in vitro in the presence of Pi, the product obtained differs both from native ferritin and from ferritin reconstituted in the absence of Pi. When the latter is incubated with Pi the product resembles native ferritin with respect both to the pattern of Pi incorporated per molecule or per Fe atom and to the ease of release of this Pi relative to Fe release. It is concluded that much of the Pi of native ferritin is adsorbed on surfaces of ferritin iron-core crystallites. The results also suggest that Pi is not present at the intracellular site of Fe incorporation into ferritin, but is added after Fe.


Iron-binding fragments from the N-terminal and C-terminal regions of human lactoferrin.

Digestion of lactoferrin with pepsin at pH3.0 gave an iron-binding half-molecule that represents the C-terminal part of the native protein. Tryptic or chymotryptic digestion of 30%-iron-saturated lactoferrin yielded the N- and C-terminal half molecules, which could be separated by DEAE-Sephadex chromatography. The N- and C-terminal fragments did not show any immunological cross-reaction. The carbohydrate of lactoferrin was distributed equally between the two fragments.


Isolation and characterization of phytoferritin from pea (Pisum sativum) and Lentil (Lens esculenta).

Ferritin was isolated from the seeds of pea (Pisum sativum) and lentil (Lens esculenta). The homogeneity of the phytoferritins was established by polyacrylamide-gel electrophoresis. The subunit molecular weights were respectively 20 300 and 21 400 for hte pea and lentil proteins. A neutron low-angle scattering study established the molecular weight of the oligomer as 480 000 for pea apoferritin and 510 000 for lentil apoferritin. Although the quaternary structure of 24 polypeptide chains is preserved, the phytoferritins have a larger cavity in the interior than mammalian ferritins and can thus potentially store 1.2-1.4 times as much iron. The amino acid composition of the phytoferritins show some similarities to those of mammalian apoferritins; tryptic 'fingerprinting' reveals that there are many differences in the amino acid sequence of plant and mammalian apoferritins.


Quantitative analysis of rat liver nucleolar and nucleoplasmic ribosomal ribonucleic acids.

rRNA from detergent-purified nuclei was fractionated quantitatively, by two independent methods, into nucleolar and nucleoplasmic RNA fractions. The two RNA fractions were analysed by urea/agar-gel electrophoresis and the amount of pre-rRNA (precursor of rRNA) and rRNA components was determined. The rRNA constitutes 35% of total nuclear RNA, of which two-thirds are in nucleolar RNA and one-third in nucleoplasmic RNA. The identified pre-rRNA components (45 S, 41 S, 39 S, 36 S, 32 S and 21 S) are confined to the nucleolus and constitute about 70% of its rRNA. The remaining 30% are represented by 28 S and 18 S rRNA, in a molar ratio of 1.4. The bulk of rRNA in nucleoplasmic RNA is represented by 28 S and 18 S rRNA in a molar ratio close to 1.0. Part of the mature rRNA species in nucleoplasmic RNA originate from ribosomes attached to the outer nuclear membrane, which resist detergent treatment. The absolute amount of nuclear pre-rRNA and rRNA components was evaluated. The amount of 32 S and 21 S pre-rRNA (2.9 x 10(4) and 2.5 x 10(4) molecules per nucleus respectively) is 2-3-fold higher  than that of 45 S, 41 S and 36 S pre-rRNA.


Processing and migration of ribosomal ribonculeic acids in the nucleolus and nucleoplasm of rat liver nuclei.

Kinetic studies on the labelling in vivo with [14C]orotate of rat liver nucleolar and nucleoplasmic pre-rRNA (precursor of rRNA) and rRNA, isolated from detergent-purified nuclei, were carried out. The mathematical methods used for the computer analysis of specific-radioactivity curves are described. Evaluation of the experimental data permitted the selection of the most probable models for the processing of pre-rRNA and the nucleo-cytoplasmic transfer of rRNA. It was shown that considerable flexibility exists in the sequence of endonuclease attacks at critical sites of 45 and 41 S pre-rRNA chains, resulting in the simultaneous occurrence of several processing pathways. However, the phosphodiester bonds involved in the formation of mature 28 and 18 S rRNA appear to be protected until the generation of their immediate pre-rRNA. The turnover rates and half-lives of all pre-rRNA and rRNA pools were determined. The turnover rate of 45 S pre-rRNA corresponds to the formation of 1100 ribosomes/min per nucleus. The model for the nucleolus-nucleoplasm-cytoplasm migration of rRNA includes a 'nucleoplasm' compartment in which the small ribosomal subparticle is in rapid equilibrium with the respective cytoplasmic pool. At equimolar amounts of nuclear 28 and 18 S rRNA this model explains the faster appearance of labelled small ribosomal subparticles in the cytoplasm simultaneous with a lower labelling of nuclear 18 S rRNA as compared with 28 S rRNA.


1. Bile salts of the green turtle Chelonia mydas (L.) were analysed as completely as possible. 2. They consist of taurine conjugates of 3 alpha, 7 alpha, 12 alpha, 22 xi-tetrahydroxy-5 beta-cholestan-26-oic acid (tetrahydroxysterocholanic acid) and 3 alpha 12 alpha, 22 xi-trihydroxy-5 beta-cholestan-26-oic acid, with minor amounts of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5beta-cholan-24-oic acid (cholic acid), 3alpha, 12 alpha-dihydroxy-5beta-cholan-24-oic acid (deoxycholic acid) and possibly other bile acids. 3. Cholic acid and deoxycholic acid represent the first known examples of bile acids common to chelonians and other animal forms: they may indicate independent evolution in chelonians to C24 bile acids. 4. The discovery of a 7-deoxy C27 bile acid is the first evidence that C27 bile acids or their conjugates have an enterohepatic circulation.


Boundary refinement of the lysozyme antigenic site around the disulphide bond 6-127 (site 1) by 'surface-simulation' synthesis.

1. We have previously shown that an antigenic site (site 1) in native lysozyme resides around the disulphide bond 6-127 and, by classical synthesis of nine disulphide peptides, the antigenic site was accurately narrowed down to the structure Cys((6))-Arg((14))-[Cys((6))-Cys((127))] -Gly((126))-Arg((128)). Only a few residues on this disulphide peptide were proposed to be involved in the reactivity with antibody. However, this lacked direct verification and the role of Arg-128 remained uncertain. 2. In the present work, several peptides were designed and synthesized by the surface-simulation concept devised in our laboratory. These enabled the precise definition of the site as well as the investigation of its conformational and directional requirements. 3. The results showed that the antigenic site (site 1) is made up of the spatially contiguous surface residues: Arg-125, Arg-5, Glu-7, Arg-14, Lys-13. The surface-simulation synthetic peptide Arg-Gly-Gly-Arg-Gly-Glu-Gly-Gly-Arg-Lys (which does not exist in native lysozyme, but copies a surface region of it) accounted entirely for the maximum expected reactivity of the site (i.e. about one-third of the total antigenic reactivity of lysozyme). An immunoadsorbent of the peptide also removed about one-third of the total lysozyme antibodies. 4. The antigenic site exhibited restricted conformational freedom. The achievement of the full reactivity of the site by surface-simulation synthesis requires the appropriate choice of spacer separation between its reactive residues. The surface-simulation synthetic site exhibits the same mono-directional preference (Arg-125 to Lys-13) for the rabbit and goat antisera so far tested. The site describes a line which encircles a part (3.01 nm in C((alpha))-to-C((alpha)) distance from Arg-125 to Lys-13) of the surface of the molecule.


The precise and entire antigenic structure of native lysozyme.

The exact boundary, residue, conformational and directional definitions of the three antigenic sites of native hen's egg-white lysozyme are described. The results clearly reveal that the three antigenic sites account quantitatively for the total antigenic reactivity of the protein. Thus the entire antigenic structure of lysozyme has now been precisely determined and is briefly discussed here, together with the power of the surface-stimulation synthetic concept.


Lysine residue 240 of human serum albumin is involved in high-affinity binding of bilirubin.

Bilirubin can be coupled covalently to albumin by using water-soluble carbodi-imide as coupling reagent. The optimal specificity in the attachment of bilirubin to the high-affinity site on the albumin molecule was obtained by treating an albumin-bilirubin complex with carbodi-imide in low concentrations and for a short period. The product was reduced, carboxymethylated and digested with trypsin. By fractionation on Sephadex G-50 (superfine grade) a peptide fraction containing most of the bilirubin label was isolated. Further purification by paper chromatography gave one peptide, consisting of residues 240-258. The peptide containined a single lysine residue, 240, and had an intact disulphide bridge. The results indicate that bilirubin is bound to lysine residue 240 at its high-affinity site on human serum albumin.


Comparison of the kinetic properties of ribulose bisphosphate carboxylase in chloroplast extracts of spinach, sunflower and four other reductive pentose phosphate-pathway species.

Extracts from chloroplasts of spinach, sunflower and four other reductive pentose phosphate (C3)-pathway species were measured spectrophotometrically with or without a modified preactivation procedure. In all six species this modification yielded Km (CO2) values in the range of 7-15 micron and maximum velocities, at 20 degrees C, of 129-431 mumol of CO2 carboxylated/h per mg of chlorophyll. In general, both the carboxylation and electron-transport capacities of sunflower were somewhat greater than that of the other species, and this is discussed in relation to the superior rates of photosynthesis believed to be displayed by the parent tissue.


Simplified preparation of a phosphatase inhibitor and further studies of its action.

1-Pyrrolidinecarbothioic acid (2-pyridylmethylene) hydrazide chelates Zn2+ but not Mg2+. This compound is about twice as effective as EDTA for inhibiting alkaline phosphatase from calf mucosa, and approx. 1000-fold more effective than EDTA for inhibiting acid phosphatase from wheat germ. The compound did not inhibit pyridoxine kinase activity in human leucocytes at the highest concentration tested (33 micron). Therefore it may be a useful tool for either examining or eliminating the effects of phosphatases in complex enzyme systems.


The influence of the type of sulphate bond and degree of sulphation of glycosaminoglycans on their interaction with lysosomal enzymes.

Significant differences occur between the interaction of several sulphated glycosaminoglycans with a particular lysosomal protein, leading to inhibition in the case of lysosomal enzymes. The order of strength of inhibition at pH4 was: heparin greater than chondroitin 4-sulphate = chondroitin 6-sulphate greater than dermatan sulphate.


Criteria to recognize the structure and micropolarity of pyridoxal 5'-phosphate-binding sites in proteins.

We show that polarography can be a useful tool for the recognition of the mode of binding of pyridoxal 5'-phosphate to proteins. Furthermore we discuss the possibilities of other techniques that can be used to study this subject.


Co-operativity and the methods of plotting binding and steady-state kinetic data.

The features that distinguish positive from negative co-operativity in double-reciprocal Eadie-Hofstee-Scatchard and Hanes plots, often incorrectly stated to be the sign of curvature or second derivatives, are explained. It is shown how to determine the 'Hill exponent' and interaciton free energies from curves in these plots, and in the simple plot of ligand binding or velocity against free ligand or substrate concentration. New types of plots, where the kind of co-operative behaviour is more obvious than in the traditional ones, are proposed.


The preparation of liposomes bearing human (HLA) transplantation antigens.

The incorporation of HLA antigens into liposomes is described. At and above the lipidphase-transition temperature, between 50 and 80% of the added antigenic activity may be incorporated into liposomes in the form of multilamellar vesicles. The antigen appears to be asymmetrically orientated with respect to the lipid bilayer.


I-cell disease. A hypothesis for the structure of the carbohydrate recognition site on beta-D-N-acetylhexosaminidase.

I-cell disease (mucolipidosis II) is presented as a model for endo- and exo-cytosis phenomena in man. A hypothesis is presented for the structure of the carbohydrate recognition site on fibroblast-derived beta-D-N-acetylhexosaminidase that may extend to the other affected hydrolases and that is responsible for specific uptake of the enzyme by fibroblasts. The proposed neuraminidase deficiency in I-cell disease is discussed in the light of its significance in influencing the final sugar sequence in the carbohydrate structure of the recognition site.


All factors required for protein synthesis are retained on heparin bound to Sepharose.

1. Postmitochondrial supernatants of rabbit reticulocyte lysates were chromatographed on heparin bound to Sepharose 4B, and the fraction retained on affinity columns was separated by subsequent gel filtration on Sepharose 4B into three fractions, two of them active in protein synthesis. 2. The heavier fraction sedimented at 40S and contained more than 10% RNA. This consisted predominantly of a 12S component, with smaller amounts of the 9S and 4S RNA species. The lighter fraction (18-20S) was composed of proteins with less than 1% RNA. 3. Different enzymic activities were associated with these fractions. 4. In the presence of both fractions, efficient translation took place on combined ribosomal subunits of rat liver with added cofactors. Globin messenger ribonucleoprotein stimulated this translation 5-6-fold. 5. Relatively large complexes of all factors required for protein synthesis are apparently isolated from reticulocytes by affinity chromatography on heparin-Sepharose 4B. Such complexes may occur naturally in the cytoplasm of mammalian cells.


The binding of monoribosomes, oligoribosomes and polyribosomes to reticular membranes from rat liver.

1. The activity of the enzyme protein disulphide-isomerase (EC 5.3.4.1) was used to measure the binding of ribosomal fractions to reticular membranes from the liver of unstarved male rats. 2. Membranes degranulated by treatment with KCl plus puromycin and washed by centrifugation through 0.5 M-KCl bound oligoribosomes but not monoribosomes. 3. Substitution of 0.25 M-KCl for 0.5 M-KCl in the wash solution produced membranes that bound monoribosomes and 60 S subunits in addition to oligoribosomes. 4. The binding of all classes of ribosomes to smooth and 'lightly granulated' rough membranes was activated by oestradiol. The hormone activation was much greater with polyribosomes from fed rats than for monoribosomes or oligoribosomes from starved rats. 5. Exposure of rough membranes to centrifugal forces caused them to undergo partial degranulation, as demonstrated by unmasking of protein disulphide-isomerase activity.


Possible interrelationship between vitamins E and b12 in the disturbance in methylmalonate metabolism in vitamin E deficiency.

1. The disturbance in 2-methylmalonate metabolism resulting in its increased urinary excretion observed in vitamin E deficiency is not caused by increased formation of methylmalonate from propionate as is evident from the activity of the enzyme propionyl-CoA carboxylase (EC 6.4.1.3), but can be traced to an impairment in the conversion of methylmalonate into succinate by the vitamin B12-requiring enzyme, methylmalonyl-CoA mutase (EC 5.4.99.2) in rat liver. 2. It is shown that the decrease in the activity of methylmalonyl-CoA mutase in vitamin E deficiency is not a consequence of a secondary vitamin B12 deficiency. Peroxidative destruction of the coenzyme in vitamin E deficiency was also ruled out. The results suggest a defect in the conversion of cyanocobalamin into its coenzyme form.


Glycosyl transfer from nucleotide sugars to C85- and C55-polyprenyl and retinyl phosphates by microsomal subfractions and Golgi membranes of rat liver.

The capacity of isolated membrane fractions to catalyse transfer of sugars from sugar nucleotides to alpha-saturated and non-saturated forms of phosphorylated C85 and C55 polyprenols and retinyl phosphate was examined. The amount of endogenous lipid acceptor present for various sugars was also measured. It appears that the types and amounts of polyprenyl phosphates present in rough- and smooth-microsomal fractions and Golgi membranes are different and the individual polyprenyl phosphates exhibit specificity as sugar acceptors.


The effect of dietary protein deficiency on albumin synthesis and on the concentration of active albumin messenger ribonucleic acid in rat liver.

In rats fed on a protein-deficient diet, albumin synthesis as a percentage of total liver protein synthesis falls from the normal value of approx. 15% to about 8%. We have extracted total cytoplasmic RNA from individual rat livers and measured the concentration of active albumin mRNA by translation in a reticulocyte lysate system from which the endogenous mRNA had been removed [Pelham & Jackson (1976) Eur. J. Biochem. 67, 247-256]. In this messenger-dependent system it is possible to measure the synthesis of albumin as a proportion of the overall protein synthesis promoted by the addition of the hepatic RNA. The results show that the concentration of translatable albumin mRNA in samples of total cytoplasmic RNA from livers of protein-deficient rats is decreased markedly. These findings suggest that dietary protein supply affects selectively the synthesis and/or functional stability of albumin mRNA in rat liver.


Mechanisms of the ability of insulin to activate the glucose-transport system in rat adipocytes.

Isolated rat adipocytes were used to assess the mechanisms of the ability of insulin to accelerate glucose transport. Glucose transport was determined by measuring the initial rates of 2-deoxyglucose uptake, and at 24 degrees C insulin increased the Vmax. of transport from 7.3 +/- 1 to 23.1 +/- 2 nmol/min per 10(6) cells, but the Km value remained unchanged (2.5, cf. 2.4 mM). When the Vmax. of basal and insulin-stimulated transport was measured as a function of temperature (15-37 degrees C), parallel Arrhenius plots were obtained yielding equal activation energies of approx. 59kJ/mol. Since both processes have equal activation energies the data indicate that insulin increases Vmax. by increasing the number of available carriers rather than enhancing intrinsic activity of already functioning carriers. Since the ability of insulin to activate glucose transport did not decrease with temperature (whereas plasma-membrane fluidity declines), it is suggested that lateral diffusion of insulin receptors within the plasma-membrane bilayer is not a rat-determining step in insulin action.


Loss of cell-population-density-dependent incorporation of fucose into the lipid fraction of cultured human tumour cells.

The incorporation of radioactively labelled fucose into the lipid fraction of cultured normal human cells and several human tumour-cell lines was examined as a function of the cell population density. Normal cells exhibited a density-dependent pattern of incorporation, whereas in tumour cells the radioactivity incorporated was independent of the cell population density. An exception was found among the tumour cells, which suggests a possible correlation between the loss of this marker and the ability to produce tumours.


The regulation of glutamate metabolism by tricarboxylic acid-cycle activity in rat brain mitochondria.

1. The interrelationship of metabolism of pyruvate or 3-hydroxybutyrate and glutamate transamination in rat brain mitochondria was studied. 2. If brain mitochondria are incubated in the presence of equimolar concentrations of pyruvate and glutamate and the K(+) concentration is increased from 1 to 20mm, the rate of pyruvate utilization is increased 3-fold, but the rate of production of aspartate and 2-oxoglutarate is decreased by half. 3. Brain mitochondria incubated in the presence of a fixed concentration of glutamate (0.87 or 8.7mm) but different concentrations of pyruvate (0 to 1mm) produce aspartate at rates that decrease as the pyruvate concentration is increased. At 1mm-pyruvate, the rate of aspartate production is decreased to 40% of that when zero pyruvate was present. 4. Brain mitochondria incubated in the presence of glutamate and malate alone produce 2-oxoglutarate at rates stoicheiometric with the rate of aspartate production. Both the 2-oxoglutarate and aspartate accumulate extramitochondrially. 5. Externally added 2-oxoglutarate has little inhibitory effect (K(i) approx. 31mm) on the production of aspartate from glutamate by rat brain mitochondria. 6. It is concluded that the inhibitory effect of increased C(2) flux into the tricarboxylic acid cycle on glutamate transamination is caused by competition for oxaloacetate between the transaminase and citrate synthase. 7. Evidence is provided from a reconstituted malate-aspartate (or Borst) cycle with brain mitochondria that increased C(2) flux into the tricarboxylic acid cycle from pyruvate may inhibit the reoxidation of exogenous NADH. These results are discussed in the light of the relationship between glycolysis and reoxidation of cytosolic NADH by the Borst cycle and the requirement of the brain for a continuous supply of energy.


Absence of parallelism between polyamine and nucleic acid contents during induced growth of cucumber cotyledons.

The cytokinins (benzyladenine or benzyladenosine) decreased spermidine and spermine contents despite increasing putrescine content, when administered to isolated cotyledons of Cucumis sativus L. var. Guntur in organ culture. KCl decreased putrescine contents, although marginally increasing polyamine contents. The cytokinins and/or KCl augmented nucleic acid biosynthesis and accumulation, resulting in enhanced growth and differentiation of the isolated cotyledons. These observations show that polyamine accumulation and growth are not always coupled.


Fractionation of microsomal membranes on the basis of their surface properties.

Partition in dextran-poly(ethylene glycol) aqueous-phase systems can be used for both membrane subfractionation and gaining information on membrane surface properties [H. Walter (1977) in Methods of Cell Separation (Catsimpoolas, N., ed.), vol. 1, pp. 307-354, Plenum, New York]. Smooth, light rough and heavy rough rat liver microsome (obtained by sucrose-density-gradient centrifugation) were subjected to countercurrent distribution in such a system. Smooth microsomal membranes had the highest, heavy rough microsomal membranes the lowest and light rough microsomal membranes an intermediate partition coefficient. The separation is based primarily on hydrophobic differences in the membrane surfaces of the three preparations and is thus due to microsomal properties not previously utilized in their fractionation. The method permits additional subfractionations of microsomes.


Intramolecular labelling of sucrose made by leaves from [14C)carbon dioxide or [3-14C]serine.

Pea leaves were illuminated in air containing 150 or 1000p.p.m. of 14CO2 for various times. Alternatively, segments of wheat leaves were supplied with [3-14C]serine for 40 min in the light in air with 145, 326 or 944p.p.m. of 12CO2. Sucrose was extracted from the leaf material, hydrolysed with invertase, and 14C in the pairs of carbon atoms C-3+C-4, C-2+C-5 and C-1+C-6 in the glucose moiety was measured. The results obtained after metabolism of 14CO2 were consistent with the operation of the photosynthetic carbon-reduction cycle; the effects of CO2 concentration on distribution of 14C in the carbon chain of glucose after metabolism of [3-14C]serine is more easily explained by metabolism through the glycollate pathway than by the carbon-reduction cycle.


Lactate-stimulated ethanol oxidation in isolated rat hepatocytes.

1. Hepatocytes isolated from starved rats and incubated without other substrates oxidized ethanol at a rate of 0.8-0.9mumol/min per g wet wt. of cells. Addition of 10mm-lactate increased this rate 2-fold. 2. Quinolinate (5mm) or tryptophan (1mm) decreased the rate of gluconeogenesis with 10mm-lactate and 8mm-ethanol from 0.39 to 0.04-0.08mumol/min per g wet wt. of cells, but rates of ethanol oxidation were not decreased. From these results it appears that acceleration of ethanol oxidation by lactate is not dependent upon the stimulation of gluconeogenesis and the consequent increased demand for ATP. 3. As another test of the relationship between ethanol oxidation and gluconeogenesis, the initial lactate concentration was varied from 0.5mm to 10mm and pyruvate was added to give an initial [lactate]/[pyruvate] ratio of 10. This substrate combination gave a large stimulation of ethanol oxidation (from 0.8 to 2.6mumol/min per g wet wt. of cells) at low lactate concentrations (0.5-2.0mm), but rates remained nearly constant (2.6-3.0mumol/min per g wet wt. of cells) at higher lactate concentrations (2.0-10mm). 4. In contrast, owing to the presence of ethanol, the rate of glucose synthesis was only slightly increased (from 0.08 to 0.12mumol/min per g wet wt. of cells) between 0.5mm- and 2.0mm-lactate and continued to increase (from 0.12 to 0.65mumol/min per g wet wt. of cells) with lactate concentrations between 2 and 10mm. 5. In the presence of ethanol, O(2) uptake increased with increasing substrate concentration over the entire range. 6. Changes in concentrations of glutamate and 2-oxoglutarate closely paralleled changes in the rate of ethanol oxidation. 7. In isolated hepatocytes, rates of ethanol oxidation are lower than those in vivo apparently because of depletion of malate-aspartate shuttle intermediates during cell preparation. Rates are returned to those observed in vivo by substrates that increase the intracellular concentration of shuttle metabolites.


Studies on the orientation of brush-border membrane vesicles.

Orientation of rat renal and intestinal brush-border membrane vesicles was studied with two independent methods: electron-microscopic freeze-fracture technique and immunological methods. With the freeze-fracture technique a distinct asymmetric distribution of particles on the two membrane fracture faces was demonstrated; this was used as a criterion for orientation of the isolated membrane vesicles. For the immunological approach the accessibility or inaccessibility of aminopeptidase M localized on the outer surface of the cell membrane to antibodies was used. With both methods we showed that the brush-border membrane vesicles isolated from rat kidney cortex and from rat small intestine for transport studies are predominantly orientated right-side out.


Biochemistry of metallocenes. Identification of the major metabolite of acetylruthenocene.

1. After oral administration of acetylruthenocene to rats, metabolites were detected in bile and urine. 2. The major metabolite, which is present in both bile and urine, is a glucuronide with the structure: C5H5-Ru-C5H4-CO-CH2-O-C6H9O6 3. The metabolite was identified by mass spectrometry of the permethylated glucuronide and mass spectrometry and n.m.r. of the aglycone. 4. The nature of the metabolite is discussed, and a comparison is made with the metabolism of the benzene analogue, acetophenone.


The effects of pyruvate concentration, dichloroacetate and alpha-cyano-4-hydroxycinnamate on gluconeogenesis, ketogenesis and [3-hydroxybutyrate]/[3-oxobutyrate] ratios in isolated rat hepatocytes.

1. In isolated rat hepatocytes incubated with pyruvate, ketogenesis increased with increasing pyruvate concentrations and decreased under the influence of 1 mM-alpha-cyano-4-hydroxycinnamate, a known inhibitor of pyruvate transport. Ketogenesis from pyruvate was higher by 30% in hepatocytes prepared from starved than from fed rats. 2. With pyruvate as substrate, 2 mM-dichloroacetate had no effect on ketogenesis of starved-rat hepatocytes, but increased ketogenesis of fed-rat hepatocytes to the 'starved' value. Gluconeogenesis from pyruvate, lactate and alanine, but not from glycerol, was inhibited by dichloroacetate. Both increased ketogenesis and decreased gluconeogenesis may result from an inhibition of pyruvate carboxylase by dichloroacetate. 3. Mitochondria were rapidly isolated from incubated hepatocytes, and [3-hydroxybutyrate]/[3-oxobutyrate] ratios were measured in the mitochondrial pellet ('mitochondrial' ratios) and in whole-cell suspensions ('total' ratios). Increasing pyruvate concentrations increased mitochondrial and decreased total ratios. In the presence of pyruvate (2 to 10 mM), dichloroacetate decreased mitochondrial and increased total ratios.


The effects of diphosphonates on the growth and glycolysis of connective-tissue cells in culture.

1. The effects of two diphosphonates (compounds containing a P-C-P bond), disodium dichloromethanediphosphonate and disodium 1-hydroxyethane-1,1-diphosphonate, on the metabolism of cultured rat calvaria cells, rabbit ear cartilage cells and rat skin fibroblasts were investigated. 2. The diphosphonates had no effect on the growth of cartilage cells and on the exponential growth of the calvaria cells and the fibroblasts. However, dichloromethanediphosphonate stopped the growth of the calvaria cells and the fibroblasts after the beginning of confluence, whereas the untreated cells were still growing to a certain extent. This inhibition was dose-dependent. After the drug was withdrawn, the cells recovered slowly. 1-Hydroxyethane-1,1-diphosphonate had no detectable effect on the growth of any of the cell types studied. Both diphosphonates decreased the cloning efficiency of calvaria cells and fibroblasts. 3. The K+ content of cartilage, calvaria and skin cells was diminished only by the highest (0.25 mM) concentration of dichloromethanediphosphonate. 4. Radioactive dichloromethanediphosphonate and 1-hydroxyethane-1,1-diphosphonate were taken up linearly with time for at least 48 h by calvaria cells and fibroblasts. The diphosphonate concentration in the cells depended on its concentration in the medium. 5. Both diphosphonates, in a dose-dependent fashion, markedly inhibited glycolysis, dichloromethanediphosphonate being more effective than 1-hydroxyethane-1,1-diphosphonate, at drug doses that had no effect on cell growth or cellular K+ content. Calvaria cells were much more sensitive than cartilage cells. When cartilage cells were cultured in an N2 atmosphere, these effects on glucose and lactate metabolism disappeared. 6. As increased acid production appears to be associated with resorption of bone, this decrease in lactate may explain why diphosphonates are effective inhibitors of bone resorption in vivo.


Total hip replacement in children with arthritis.

Fourteen children with juvenile rheumatoid arthritis and two with ankylosing spondylitis received 29 total hip replacements (THR). The ages at THR were 12 to 18 years, the median duration of prior hip disease was 7.1 years, and the minimum followup was one year (range 1--4 years, median 2.2 years). The primary indication for THR was pain in 5 hips and severe malposition or flexion contractures in 24 hips. (Sixteen of these also had some degree of pain.) All 29 hips demonstrated improved postoperative range of motion, and all were free of pain. In children, active rheumatic disease in other joints, prosthesis longevity, and possible lack of adequate motivation all merit special consideration prior to THR, but the results are encouraging.


Pathologic features of a familial arthropathy associated with congenital flexion contractures of fingers.

Three siblings with a recently recognized form of familial arthropathy were studied clinically and by light and electron microscopy of the synovium. On light microscopy, the synovium from all 3 children showed synovial hyperplasia, necrotic villi, deposition of eosinophilic and PAS-positive material, and large numbers of multinucleated giant cells. Electron microscopy of the synovium in one patient revealed giant cells with profuse rough and smooth endoplasmic reticulum. Some phagocytic cells contained degenerated collagen in vacuoles or invaginations. There was granular and fibrinlike material on the synovial surface, but no amyloid. This symmetrical arthropathy now reported in three families appears to have characteristic histological appearance of synovium that allows its identification as distinct from other known joint diseases.


Enhancement of urate solubility by connective tissue. I. Effect of proteoglycan aggregates and buffer cation.

Proteoglycan aggregates (PGC) facilitated dissolution of 2 1/2 times more sodium urate crystals than nonaggregated proteoglycans. This effect of aggregates on urate solubility was abolished by digestion of the aggregates with hyaluronic acid beta1 leads to 3 hydrolase. PGC, however, did not sustain urate concentrations in supersaturated solutions. Potassium urate was severalfold more soluble than sodium urate. In vivo, where they exist predominantly as their sodium salts in the extracellular connective tissue, proteoglycans may not markedly influence the solubility of sodium urate.


Vertebral ankylosing hyperostosis (Forestier's disease) and HLA antigens in Pima Indians.

Vertebral ankylosing hyperostosis is a common skeletal disorder among Pima Indians. Prevalence rates of approximately 50% have been reported in Pima Indian males aged 44 or older. The HLA-B27 antigen is also found more commonly in Pima Indians than in Caucasians (18% versus 6%). Because of the increased prevalence of both vertebral ankylosing hyperostosis and HLA-B27 in Pima Indians, a possible association between the two was thought to exist. Therefore, histocompatibility testing was done on 44 adult male Pima Indians age 55 or older with classic vertebral ankylosing hyperostosis and 33 age-matched controls. No significant association between any histocompatibility antigen phenotype or haplotype and vertebral ankylosing hyperostosis was found. This disease, therefore, connot be classified with the HLA-B27 associated spondylarthropathies.


Age, sex, and race effects on mortality from systemic lupus erythematosus in the United States.

Nationwide rates of death from systemic lupus erythematosus (SLE) were estimated from National Center for Health Statistics mortality data for 1968 to 1972 according to age, sex, and race. The overall rates for females, 6.3 per million person-years (whites 5.2, blacks 14.8), were about four times that for males, 1.6 per million person-years (whites 1.5, blacks 2.2). The overall rate for blacks, 8.8, was 2.6 times that for whites, 3.4. An earlier rise in age-specific mortality rates for females than males produced higher age-specific female-to male sex ratios in the early adult years than in later years. Mortality generally increased with age in whites whereas the phenomenon of an accentuation and decline during the early and middle adult ages was seen in blacks, particularly females. Analysis of age-, sex-, race-specific rates using one measure of synergistic interaction, S, revealed substantial synergy between the effects of sex and race on mortality during the childbearing ages (S = 3.2, 95% confidence interval = 2.3--4.4).


[Experimental study on hepatic encephalopathy: EEG and blood amino acid findings].

The AA. describe a method of gradual occlusion of the portal vein in the rat to induce a hepatic encephalopaty. This method allows to realise a condition of hepatic ischemia and a portal hypertensive state accompanied by spontaneous portal-systemic shunts. These two factors produce a hepatic encephalopaty like in cirrhotic state or in patients after portal systemic anastomosis. A part from similar behavior at the beginning of the encephalopaty it is possible to define two classes of animals: one showing a slow recovery and one showing a transient and slight improvement followed at the end by the death of the animal. The AA. found a definite correlation amoung the clinica, EEG's, serum aminoacids and biochemical data. Probably the different anatomical and phisiological aspects of the induced portal systemic shunts and the different ways of hepatic rivascularization may determine the two different evolutions of the animals.


Effect of cycloheximide on the bone marrow toxicity of nitrogen mustard.

Cycloheximide (CHM), a potent inhibitor of protein synthesis, has been reported to protect rat intestinal crypt cells from mitotic inhibition by nitrogen mustard (HN2). For investigation of the effect of CHM on the bone marrow toxicity of HN2, CHM (1.0 mg/kg) and HN2 in doses up to 2.5 mg/kg were given i.p. to rats. Twenty-eight % (13 of 46) of rats given HN2 alone died within 5 days. Only 4% (2 of 45) of rats pretreated with CHM died within 5 days after the administration of HN2. Rats pretreated with CHM had significantly less leukopenia and granulocytopenia than did rats given HN2 alone, and their bone marrow cellularity, assessed by histological sections and total femoral marrow cell counts, was greater than that of animals given HN2 alone. Bone marrow DNA synthesis, as measured by in vitro [3H]thymidine incorporation, was decreased 2 hr after HN2 injection, appeared to recover at 4 hr, but was further decreased at 24 and 48 hr. CHM given up to 20 min before HN2 reversed the effect of HN2 on DNA synthesis at 2 and 4 hr. A variable protective effect of CHM was observed at 24 and 48 hr. These studies indicate that CHM increases the survival of HN2-treated rats and partially protects rat bone marrow cells from HN2 cytotoxicity.


Technetium-99m stannous pyrophosphate imaging of experimental infective endocarditis.

Technetium-99m stannous pyrophosphate (99mTc-PYP) cardiac scintigraphy was performed in 15 rabbits with experimental Streptococcus sanguis aortic valve infective endocarditis. The animals were imaged five to seven days after the administration of bacteria, and in each case abnormal accumulation of the tracer was visualized in the region of the aortic valve. Three types of cardiac scintigraphic patterns were demonstrated: focal, multifocal and extensive, each correlating well with the anatomical extent of the lesion as defined by gross pathology. Tissue distribution studies demonstrated a 30 +/- 5.3 (mean +/- SEM) fold excess of radionuclide uptake in the infective endocarditis lesion compared with that of normal myocardium. Imaging of excised hearts from four animals showed an excellent correlation with in vivo imaging as well as gross pathology. Five animals with nonbacterial thrombotic aortic valve endocarditis demonstrated similar scintigraphic and tissue distribution results. In contrast, four normal animals failed to demonstrate abnormal 99mTc-PYP cardiac scintigrams or tissue uptake. This study demonstrates that 99mTc-PYP cardiac scintigraphy is a sensitive technique to detect experimental aortic valve endocarditis.


[Changes of the intestinal mucosa-bacterial flora ecosystem in rats fed various diets].

A study has been made of the distribution of bacterial flora in the gastro-enteric tract of rats fed on glycidic, protein and lipidic diets and compared with that found in rats given a standard diet. The flora of the gastro-enteric tract was noted in a fraction adhering to the epithelial cells of the mucous membrane and in a fraction present in the contents of the gastro-enteric tract. Changes resulting from the differences in diet are made particularly at the expense of the adhering flora. In groups fed on a glycidic diet there is a clear prevalence of enterococci, enterobacteria, lactobacilli, peptostreptococci and yeasts. In rats fed on a protein diet the quantity and variability fo the flora are less and clostridia predominate. Where rats are given a lipidic diet there is a prevalence of enterobacteria, lactobacilli and peptostreptococci. An extensive and diversified colonization is noted as a further consequence of differences in diet. The results obtained are discussed in relation to certain pathological intestinal conditions and to results reported elsewhere in the literature.


R factors from Enterobacter group.

Twenty-six R factors transmissible to E. coli K12 were derived from 79 strains of Enterobacter species isolated in various clinical specimens (urine, sputum, blood, pus); 71 of 79 strains were Enterobacter cloacae. Fifteen R factors were fi+: 14 belonged to group FII, 1 to group FI. Eleven R factors were fi-: 5 belonged to group M, of the others 6 (all controlling the cloramphenicol-resistance) 1 was recognized of group K, 1 was incompatible with standard plasmids of both groups S and W, and 4 belonged to group S.


Clearance of viable salmonella typhi Ty 2 and Staphylococcus aureus by the isolated rat liver in the absence of serum factors.

The clearance of S. typhi Ty 2 and of a S. aureus strain by the isolated rat liver perfused in vitro with a synthetic serum free perfusate was studied. Bacteria were added to the perfusate at the initial concentration of 1x10(8) cells/ml. During perfusions the perfusate was sampled; after 30 min bile and liver samples were obtained and used for viable bacterial counts. After 30 min the amount of bacteria phagocytized greatly differed from one strain to the other: 30% for S. typhi Ty 2 and 100% for S. aureus. The end amount of viable bacteria recovered in the isolated liver was 7% for S. typhi Ty 2 and 80% for S. Aureus, thus indicating that for the latter strain greater clearance was not associated with an equally fast intracellular death.


Histocompatibility (HLA) factors in ataxia telangiectasia.

In the recent studies conducted in patients with various types of primary immunodeficiency diseases, an increased frequency of HLA-A1 or HLA-A2 antigens was reported. In order to determine the frequency of the histocompatibility antigens in ataxia telangiectasia (A-T), HLA typing was carried out in 30 patients with A-T along with their 23 parents and 4 siblings. The results were compared with 138 healthy controls. That study showed no significant difference for the frequencies of 19 HLA antigens of the A and B loci between the controls and A-T patients or their parents-siblings.


Serum antibody level in rabbits submitted to antitetanus active-passive immunization with heterologous horse serum.

Serum antibody titres have been assessed in rabbits submitted to active and active-passive immunization against tetanus with AlPO4 adsorbed vaccine and horse heterologous immune serum. Heterologous antibodies survive in the blood stream no more than six days. Endogenous antibodies, with the adopted vaccination schedule, emerge fifteen days after the first vaccine inoculation. In rabbits undergoing active-passive immunization, the appearance time of endogenous antibodies is delayed, all the more so as the antiserum injected dose increases. Such data stress the opportunity to give up with the use of heterologous immune sera in tetanus prophylaxis, in association with vaccine as well.


Sheep red blood cell membrane structure: an immunological probe.

Pronase digested sheep red blood cell stromata were employed as probe in order to investigate erythrocyte membrane arrangement by immunological way. Antiserum from rabbits immunized with erythrocyte ghost pronase residue assayed for its hemolytic activity against intact sheep red cells, showed an high titer, in a good agreement with the presence in the same residue of externally located membrane antigens. Immunoelectrophoretic analysis was performed between the solubilized residue and precipitins produced by rabbits immunized respectively with the following antigens: intact sheep red blood cells (SRBC), sheep erythrocyte stromata (SRBCS), lipid complex (LC), sphingomyelin complex (SF), stromata after phospholipase A treatment (SPLA), stromata after phospholipase C treatment (SPLC), stromata after phospholipases A and C treatment (SPLAC), and pronase treated stromata (SP). Antigen/antibody reaction with anti-SP antiserum showed an additional precipitation line: this fact is discussed in view of a possible enrichment of the fraction after pronase stromata digestion, and/or enhancement of the immunogenicity.


[Evaluation of non-treponemal VDRL and RPRC reactions].

The non-treponemal reactions VDRL and RPRC for the serological diagnosis of syphilis were compared in serum samples having low-titer antibodies and/or antibody dissociations. The analysis of the serological results obtained by performing non-treponemal (VDRL, RPRC) and treponemal (FTA-5, FTA-ABS) tests indicates the best choice of reactions for the serology of lues, which may be summarized as follows: a) The VDRL is the most sensitive and specific test of the non-treponemal reactions which employ cardiolipin antigen. b) A screening serology of syphilis, performed by associating two selected tests (VDRL, FTA-5), demonstrates more positive cases than the use of only one test. c) The serological identification of the antibodies present in luetic sera, obtained by associating selected treponemal and non-treponemal tests (VDRL, FTA-5, FTA-ABS, CF-ATPS) enables us to correlate the serological data with the main biological phases of lues, even during the periods of clinical latency of the disease.


[Spontaneous blast formation of spontaneous rosette-forming human lymphocytes with sheep and mouse erythrocytes: morphological demonstration].

A high uptake rate of 3HTdR by human cultured rosette-forming lymphocytes with sheep or mouse erythrocytes without stimulation has been already found occasionally in a discrete percentage of experiments by the Authors. In this paper morphologic evidence is shown that in those cultures "blastic" or "blast-like" cells are present, probable expression of spontaneous lymphocyte activation by "rosetting" phenomenon.


[Cryoglobulinemia and mesangio-capillary glomerulonephritis (comparison of the 2 histological types)].

Sera from 21 patients with mesangiocapillary glomerulonephritis were examined for the presence of cryoglobulins, for the complement levels and in 8 cases for the C3 splitting activity. Patients were divided, on the basis of histology, into two groups; the first of 10 patients with subendothelial deposits, the second of 11 patients with intramembranous dense deposits. The incidence of cryoglobulins and the cryoprecipitate components were similar in the two groups. As previously described, in the first group low levels the C3 was low without alterations in the C4 levels. There are no previous reports on this high incidence of cryoglobulins in dense deposits disease and these data add further support to the hypothesis that this disease is, at least partially immunecomplexes mediated.


Chromosome radiation-induced aberrations in patients with Hodgkin's disease. Possible correlation with second malignancy?

The karyotype of peripheral blood lymphocytes has been studied in a group of patients with Hodgkin's disease. Before any therapy, the karyotype was either normal or aneuploid. A few months after radiotherapy (total nodal irradiation) a conspicuous amount of structural chromosome aberrations was found. Three to six years after completion of radiotherapy, the lymphocyte karyotype was almost normal, even if stable ionizing radiation-induced aberrations were still detectable. This is consistent with the normal behaviour of these patients and with the long-lasting effect of radiations on nuclear D.N.A. Owing to the close relationship between ionizing raditions and chromosome aberrations on one hand, and abnormal karyotypes and tumors on the other, it cannot be overlooked that these aberrations may play an important role, together with other carcinogenic factors, in the development of second malignancies in these patients.


[Serological studies of influenza viruses in a sample of the population of Rome].

Haemagglutination inhibiting antibodies (H.I.A.) to influenza viruses A/Victoria/3/75, A/Victoria/112/76, B/Hong Kong/8/73 and A/New Jersey/8/76 were titrated in 1110 serum specimens collected in Rome in the period between March-May 1977 and obtained from subjects 0-60 years old. The H.I.A. protective level (greater than or equal to 1 : 40) found in 21.7% of the sera against A/Victoria/3/75 is such that it does not avoid a possible diffusion of this strain in the successive epidemic season. Moreover this finding suggests that there will be probably no antigenic change (4) in the same period. The age group 0-20 showed the higher titer H.I.A. Low protective levels were found against the virus A/Victoria/112/76 and B/Hong Kong/8/73, while the H.I.A. to virus A/New Jersey/8/76 showed a percentage of protective level increasing with the age.


[Incidence of hemagglutination-inhibiting antibodies in the population of Milan and of Bari against strains of influenza viruses of epidemiological importance in the winter of 1977-78].

A sero-epidemiological survey was carried out on 555 serum samples from normal subjects of both sexes (age: from few months to over 60 years) collected in the late summer 1977 in Milan and Bari, two towns with rather different climatic conditions. In both localities a further large spread of A/Victoria/3/75 strain seems unlikely, since 54% of sera from Milan and 58% of those from Bari have h.i.a. at protective titers. On the contrary, the degree of immunity against B/Hong Kong/8/73 virus is still faiitical level for the survival of A/Hong Kong/68 pandemic strain appears almost reached in the population of Milan, where 76% of subjects have antibody at protective titers. In Bari such percentage is 60%. The statistical analysis (X2 test) of the data concerning the subjects with h.i.a. at titers greater than or equal to 1:40 shows only one significant difference between Milan and Bari, that is the A/Hong Kong/68 antibody prevalence. Probably this is due to the low number of males of Bari with protective antibody levels.


[Nerve fibers and nerve endings in the choroid plexus--electron microscopic study (author's transl)].

Nerve fibers and nerve endings in the fourth ventricle choroid plexus of the adult rat were studies with the electron microscope. Nerve endings were found at two sites within the plexus : 1) on the vascular wall (i. e., vascular nerve endings), and 2) in the stroma between the choroidal epithelium and the fibrovascular core (i. e., stromal nerve endings). Ultrastructurally all fibers were of the efferent type, and the majority were unmyelinated. No ganglion cell bodies were identified. Fibers ending in relation to the smooth muscle of the vessels presumably control the calibre of these vascular channels. Although the role of the stromal nerve endings is as yet unknown, these fibers may influence epithelial cell functions and thus indirectly regulate choroidal cerebrospinal fluid production.


[Endocrinological evaluation of pituitary function in the prognosis of hypothalamo-pituitary disorders (author's transl)].

Chronological endocrine changes accompanying various diseases in the hypothalamo-pituitary region (183 cases) were collectively studied by evaluating both endocrinological symptoms and anterior pituitary functions, with the following results : 1) Endocrine disorders following the operation, trauma and subarachnoideal hemorrhage in the pituitary-diencephalic region varied in the order of a) subclinical, b) clinical and c) paradoxical. This trend was especially marked in young cases of pituitary adenoma and of craniopharyngioma. 2) In young patients, the secretion of anterior pituitary hormones was markedly improved, particularly, TSH showed hypersecretion. The clinical symptom, however, remained unimproved. 3) The alteration associated with the adhesion of pituitary-diencephalic region was significant for the endodrine disorders. Such alteration was observed at 2--6 months after traumatic subarachnoideal hemorrhage. 4) The endocrine disorder developed and exacerbated in 6 months to 2 years after radio therapy of the pituitary-diencephalic region. 5) For the estimation of recurrence of tumors in the pituitary-diencephalic region endocrinological assessment was very useful.


[Kraepelin's calculating test as an indicator of shunt-operation effect for normal pressure hydrocephalus (NPH) (author's transl)].

Many reports have been issued since the first report on NPH by Adams et al. in 1965, and shunting operation is reported as the most efficient procedure for this condition. However, still some problems are remained to be solved, for example we have no generally accepted objective evaluating method for mental activity of NPH--patient in pre- and post-shuntoperation. The author chose Kraepelin's calculating test, which is continuing adding of at random series of one figure numbers and result rate of every minute and correct or erroneous rates are used as the indicator for mental capacity according Yokota's standard. The reproducibility and stability of this test are realized again on the cases of this report. The most essential appreciation for the treatment of NPH is mental activity itself and not size of the ventricle nor improving of EEG. This report has proved that the Kraepelin's calcuculating test with Yokota's standard is stable objective indicator for mental activity of NPH--patient, and pre- and post-shuntoperation evaluation was mentioned.


[Auditory response at the posterior part of the first temporal convolution (author's transl)].

Among the epileptic patients investigated by the stereotactic E. E. G. (Talairach) whose electrodes were introduced at or around the auditory cortex (Area 41, 42), the topography of the auditory responses by the electrical bipolar stimulation and that of the auditory evoked potential by the bilateral click sound stimulation were studied in relation to the ac--pc line (Talairach). The positive points of auditory responses and those of evoked potential were found in the posterior part of the first temporal convolution at or around the Hesch's transverse gyrus. The contralateral auditory responses to the stimulating electrodes situated more anterior and superior than the homolateral responses in lateral projection and more medial in frontal projection. The points of the sensation of "elevation" or "fall" elicited by the electrical stimulation which were thought to be related to the vestibular function were scattered more superior and posterior than the points of the auditory responses in lateral projection and more medial in frontal projection. This study gave the accurate topography concerning the auditory responses, the positive auditory evoked potentials and the vestibular function related sensation (sensation of "elevation" or "fall"). Further study will be required to elucidate the functional anatomy of the human auditory cortex.


[An autopsy case of bilateral cavities in the temporal white matter and the striatum (author's transl)].

A 24-year-old female developed high fever and unconsciousness for several days at the age of 3. She was said to have meningitis. Subsequently her verbal development was markedly retarded so that she was kept at a deaf-and-dumb institute. At the age of 19, she was transfered to the mental hospital because she occasionally became very wild without any reasons. She suddendly died at the age of 24 due to paralytic ileus. Her autopsy showed bilateral cavities in the white matter of the anterior portion of the temporal lobes and the striatum. Microscopically, the tissues around the cavities were necrotic and devastated with loss of neurones. Glio-mesodermal reaction was mild. Besides marked thickening of meninges and micropolygyria of the cerebellar hemispheres were demonstrated.


[Effects of bilateral amygdalectomy on levers pressing for food reward in the rabbit (author's transl)].

Effects for continuous reinforcement (CRF) learning and differential reinforcement of low rate (DRL) learning for food in the rabbit by bilateral amygdalectomy were examined with the Skinner box. There was no changes in general behaviour and no impediment of CRF learning. But the completion of DRL learning was delayed by amygdalectomy. In the stage of completion of DRL learning there was no difference of total number of the reinforcement and the lever pressing between the control group and amygdalectmized group. But there was the impediment of DRL learning by the analysis of frequency distribution of inter-response time and of transition probability matrix in the amygdalectimized group. We thought that this impediment of DRL learning was due to the impediment of selection of decision of lever pressing action. The memory of the preamygdalectomy was maintained well after amygdalectomy.


Effects of gravitational stresses on mitral valve prolapse. I. Changes in auscultatory findings produced by progressive passive head-up tilt.

The effects of passive head-up tilt on systolic time intervals were assessed in 18 patients with mitral valve prolapse. In addition to causing prolongation of the pre-ejection period and shortening of left ventricular ejection time, this circulatory stress led to progressive shortening of the Q to click interval. In 1 patient, a systolic click became audible which had not been heard in the supine posture. In 7 patients the click disappeared during head-up tilt, usually at 60 degrees or 90 degrees. In 2 patients without a murmur while supine, a mid-late systolic murmur appeared with tilt; 1 of these 2 as well as another patient who had a soft late systolic murmur while supine developed loud systolic whoops at greater angles of tile. The correlations between Q to click interval and aortic valve opening to click interval, and both the angle and the sine of the angle of tilt were highly significant.


Left coronary artery anatomy in patients with bicuspid aortic valves.

The anatomy of the proximal left coronary artery in 33 adult patients with bicuspid aortic valves was compared with that in 33 adult patients with aortic valve disease of other aetiologies and with that in 50 adult control patients with no valve or congenital heart disease. Patients with bicuspid aortic valves had a higher incidence of immediate bifurcation of the left main coronary artery, of left main coronary length less than 10 mm, and of left coronary artery dominance. The mean length of the left main coronary artery was significantly less in the patients with bicuspid aortic valves. These variations from the usual coronary artery anatomy may be part of the developmental abnormalities responsible for bicuspid aortic valves, and require evaluation and consideration when considering angiography and valve replacement in patients with aortic stenosis.


Transposition of the great arteries with ventricular septal defect and pulmonary stenosis.

A postmortem investigation was carried out of 19 heart specimens with transposition of the great arteries, ventricular septal defect, and congenital subvalvular pulmonary stenosis. Certain types of obstruction appeared to be closely related to other features of the hearts. In cases with malalignment of the infundibular septum, the obstruction was caused by this septum and the anterolateral muscle bundle of the left ventricle. If the infundibular septum was deviated considerably to the left, the pulmonary stenosis was usually severe because the infundibular septum and anterolateral muscle bundle were joined. This junction resulted in a relatively posterior position of the pulmonary orifice in the left ventricle. A less extreme deviation of the infundibular septum resulted in an obstruction by this septum and by the anterolateral muscle bundle, situated at the right and the left sides of the pulmonary orifice respectively. In some cases of paratricuspid ventricular septal defect an anomalously attached and cleft anterior leaflet of the mitral valve was found. This, together with a leftward deviation of the anterior left ventricular part of the ventricular septum, caused the obstruction.


Cardiovascular malformations in Turner's and Noonan's syndrome.

The cardiovascular findings in 9 patients with Turner's syndrome and 9 patients with Noonan's syndrome are described. Of the 9 patients with Turner's syndrome, 4 had coarctation of the aorta, 4 aorta stenosis, and the remaining patient both these lesions. All patients with Noonan's syndrome had pulmonary valve stenosis. In addition, 2 children had an atrial septal defect and 1 an atrial septal defect associated with mild supravalvar pulmonary stenosis and anomalous drainage of the right upper pulmonary veins. In the majority of patients the electrocardiogram was different from the pattern usually seen in pulmonary valve stenosis: the QRS axis in the frontal plane was superiorly oriented in 7 out of 9 cases and in 2 patients evidence of right ventricular hypertrophy was lacking in the right praecordial leads; in 5 patients an rS complex was seen in the left praecordial leads. Gross thickening of pulmonary valve cusps was found at operation in 4 of the 8 patients who were operated on. Although phenotypically related, Turner's and Noonan's syndromes are associated with different and distinct cardiovascular anomalies.


Uses of coronary heart attack registers.

By studying all coronary heart attacks presenting within defined communities it should be possible to avoid the distortions and omissions inherent in hospital-based case series. In practice the technique presents several problems. Measures of frequency and outcome are very sensitive to the diagnostic criteria used. Data of varying quality are mixed and specific attack rates can be calculated only for items for which the census provides a denominator. Patients presenting to different medical services have different outcomes, but probably less because of treatment than because the severity of the attack affects behaviour in it. Despite these problems, some such intelligence system is of value in any comprehensive strategy for coronary heart disease.


Large ventricular aneurysms occurring after myocardial infarction.

We have studied 33 patients with a large ventricular aneurysm complicating an anterior myocardial infarction. The features of myocardial infarction progressing towards an aneurysm were no previous history of coronary disease, severe infarction as shown by the severity of pain and the presence of pericardial rub and heart failure, and large increase in serum levels of cardiac enzymes. A large aneurysm usually follows a large infarction resulting from the total or partial occlusion of the left anterior descending artery, which is involved alone in about half the patients and is associated with lesions of the circumflex and right coronary arteries in the other half. In most cases, standard radiography showed an abnormal cardiac configuration, but in 7 patients (21%) there was no radiological evidence of aneurysm. ST segment elevation (mean 2.7 mm) was reported in all subjects but one. Heart failure was present in most patients and was an indication for surgical treatment in one-third of the patients. A large aneurysm was not a contraindication to operation even when at angiography the aneurysm seemed to occupy almost all the left ventricle. Twenty-one patients were operated upon for resection of the aneurysm with a mortality rate of 14 per cent.


Role of Coxsackie B viruses in myocardial infarction.

Serological evidence of Coxsackie B virus infection was found in 13.5 per cent of 52 patients with acute myocardial infarction and in 19 per cent of 52 controls with chest pain but normal electrocardiograms. In contrast to an Australian report, but in agreement with previous findings in Glasgow, it seems unlikely that Coxsackie B viruses contribute significantly to the causation of myocardial infarction.


Long-term follow up of cardiac pacing threshold using a noninvasive method of measurement.

Seventeen patients were followed up for a period ranging from 12 to 40 months after implantation of an Elema Vario pacemaker with an endocardial electrode. Two patients had a greater stimulation threshold beyond 6 months after implantation than the maximum threshold recorded before 6 months. One of these patients required replacement of the pacing system because of exit block. The 16 patients who retained their pacing systems showed, as a group, a statistically significant fall in stimulation threshold at 12 months after implantation despite continued pacing. These findings are important in relation to the occurrence and prediction of late exit block when long-life impulse generators are used.


Leucocyte migration inhibition test in cases of ischaemic heart disease.

Cases of ischaemic heart disease have been studied for the cell-mediated immune response against human heart antigen by using the leucocyte migration inhibition test. In 30 cases of acute myocardial infarction, the leucocyte migration inhibition values started increasing from the first week reaching a peak in 3 to 4 weeks and then declining but still above control values 12 months after infarction. The leucocyte migration inhibition values were significantly higher than control values in another 10 patients with late complications of previous infarction and in those patients with acute myocardial infarction who were less than 40 years of age, who had extensive anterior infarction, or who had a past history of angina pectoris. The leucocyte migration inhibition values were negligible in all the 12 patients with stable angina pectoris, but were high in 2 of the 8 with unstable angina and in 3 of the 4 with the intermediate coronary syndrome. The leucocyte migration inhibition values were much higher in patients with complications, which may be the result of cardiac damage by a cell-mediated immune response.


Anticoagulants and the Björk-Shiley prosthesis. Experience of 390 patients.

From September 1972 to January 1975, 390 patients underwent valve replacement using the Björk-Shiley tilting disc prosthesis. For the group as a whole hospital mortality was 13.3 per cent and was lowest in those undergoing isolated mitral or aortic valve replacement (5.3 and 9.4%, respectively). Available for follow-up were 209 patients of whom 123 were maintained on dipyridamole and 96 on warfarin. Thromboembolic complications were significantly (P less than 0.01) commoner in the dipyridamole (28 of 123, 22%) than warfarin (6 of 86, 7%) treated group. In the dipyridamole treated group the incidence of thromboembolic complications was similar whichever valve was replaced and thromboembolic complications were responsible for 14 of the 28 late deaths. In the warfarin treated group thromboembolic complications only occurred in patients with a mitral prosthesis. Anticoagulation is indicated for all patients with this prosthesis wherever inserted.


Regional variations in mortality from ischaemic heart and cerebrovascular disease in Britain.

In middle-aged men and women, mortality from ischaemic heart disease and cerebrovascular disease is highest in the north and west of Britain. The worst region is West Central Scotland. Statistical analysis using a linear logistic model shows that the differences between the regions are significant and the yearly fluctuation in numbers of deaths contributes little to the overall variation.


Effect of morphine on splanchnic blood flow.

Splanchnic blood flow was measured by the constant infusion of indocyanine green given before and after morphine 0.2 mg/kg (maximum 15 mg) intravenously in 13 patients. Splanchnic blood flow increased from 1012 +/- 98 ml/min to 1200 +/- 118 ml/min after the administration of morphine, a 19 per cent increase (P less than 0.025). Splanchnic vascular resistance decreased from 0.094 +/- 0.010 to 0.081 +/- 0.010 mmHg min/ml, a 16 per cent decrease (P less than 0.001). There was no significant change between baseline and post-morphine values in systemic arterial pressure (92.2 +/- 3.8 and 89.0 +/- 2.9 mmHg), hepatic vein wedge pressure (7.1 +/- 1.0 and 7.8 +/- 0.6 mmHg), or right atrial mean pressure (4.5 +/- 0.6 and 4.3 +/- 0.7 mmHg). This study shows that morphine induced significant splanchnic arteriolar dilatation.


Diazoxide in treatment of primary pulmonary hypertension.

Three patients with primary pulmonary hypertension and one man with suspected thromboembolic pulmonary hypertension were given up to 300 mg diazoxide by injection into the pulmonary artery. The three patients with primary pulmonary hypertension responded with a fall in total pulmonary resistance and a rise in cardiac output. The patient with suspected thromboembolic pulmonary hypertension did not respond. Haemodynamic and clinical improvement was maintained by oral diazoxide in two of the responders, and in one the prognosis appeared to be greatly improved.


Left atrial myxoma with aortic regurgitation.

A 59-year-old woman with a left atrial myxoma was shown to have moderate aortic regurgitation. At operation for removal of the myxoma it was found to be attached to the atrial septum close to the aortic root. It is suggested that the aortic regurgitation was caused by distortion of the aortic root caused by traction upon it from the myxoma as it moved downward into the left ventricle in diastole. Observations are made on the echocardiographic findings which helped in the diagnosis of the left atrial myxoma.


Tricuspid valve excision without replacement in a case of endocarditis secondary to drug abuse.

A patient is presented in whom urgent surgical intervention was necessary to alleviate the consequences of tricuspid valve endocarditis. Six months after operation she remains well, without a valve prosthesis.


A case of surgically corrected Wolff-Parkinson-White syndrome. Clinical and histological data.

A case of type B Wolff-Parkinson-White syndrome, with intractable atrial fibrillation, underwent surgical division of a right-sided accessory atrioventricular bundle of Kent. Pre-excitation and complicating tachyarrhythmias were henceforth abolished for 6 weeks, when the patient died of infective endocarditis. Histological examination showed a divided Kent's accessory atrioventricular pathway and apparently functionless James and Mahaim fibres.