Vitamin D metabolites and bone mineralization in man. A comparison was made of the biochemical and osseous effects of 25-hydroxyvitamin D3 [25(OH)D3], 1 alpha-25-hydroxyvitamin D3 [1 alpha, 25(OH)2D3], and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] in adult vitamin D-deficient man. Administration of 50 micrograms/d of 25(OH)D3 for 8 weeks led to a return of the mineralization front to normal associated with a return of TmPO4/GFR to normal, an increase in serum phosphate and calcium concentrations, a fall in serum IPTH, and a rise in serum alkaline phosphatase activity. Giving 2.5 micrograms/d of 1 alpha,25(OH)2D3 did not produce these effects. Administration of 1 alpha, 25 (OH)2D3 caused an increase in intestinal calcium absorption, and a rise in serum calcium associated with a fall in serum immunoreactive parathormone (IPTH) concentrations but no sustained rise in either alkaline phosphatase, serum phosphate concentration, nor in TmPO4/GFR. Its administration caused an increase in the extent of the osteoclastic bone resorption surface but the extent of the mineralization front remained subnormal. Administration of 20 micrograms/d of 24,25(OH)2D3 caused a fall in urinary calcium excretion and in serum IPTH, and a rise in serum alkaline phosphatase, but no change in TmPO4/GFR or serum phosphate, and only a slight increase in the extent of the mineralization front. Combined treatment with 1 alpha, 25(OH)2D3 and 24,25(OH)2D3 led to a return of the mineralization front of normal even though both TmPO4/GFR and serum phosphate concentration remained low. It is concluded that 1alpha,25(OH)2D3 is not the sole biologically active metabolite of vitamin D in man. It is apparent that either 25(OH)D3 or some as yet unidentified metabolite of 25(OH)D3 stimulates the renal tubular reabsorption of calcium and phosphate, and that the subsequent rise in serum phosphate concentrations along with the direct actions of 1 alpha-25(OH)2D3, 24,25(OH)2D3, and possibly 25(OH)D3 on bone cells all participate in the restoration of normal bone formation and bone mineralization in vitamin D-deficient man.


Volume as a determinant of plasma aldosterone in anephric man. Previous studies from this laboratory have demonstrated that the redistribution of blood volume and concomitant central hypervolemia induced by water immersion to the neck (NI), produces a prompt and profound suppression of plasma renin activity (PRA) and plasma aldosterone concentration (PA) without concomitant alterations in serum sodium and potassium concentrations. The NI model was utilized to assess the responsiveness of PA to volume expansion in 12 anephric subjects. The patients were studied on 2 occasions, 48 h after their last dialysis: during a seated control study (7 of the patients) and during 3 h of NI (all 12 patients). The conditions of seated posture and time of day were identical. Blood for PRA, PA, and cortisol was obtained at 30-min intervals for 5 h. PRA was undetectable in all patients. NI failed to alter PA. Plasma cortisol declined progressively throughout NI; serum potassium concentration remained unchanged. An identical NI study in normal subjects suppressed PA by 60%. These data demonstrate that when plasma composition and posture are maintained constant, marked central hypervolemia does not alter PA in anephric man. The present findings support the role of the renin-angiotensin system as the prepotent mediator of volume-induced changes in PA.


Cord blood reverse T3 in congenital hypothyroidism. Reverse triiodothyronine (rT3) was measured in cord serum from 5 infants with congenital hypothyroidism and compared with normal values in 70 euthyroid control infants. The mean (and SEM) value in the affected infants (135 +/- 12 ng/dl) was significantly lower than that in the control population (270 +/- 9 ng/dl). However, the large overlap in range of concentrations in affected and control infants indicates that newborn screening based on the determination of rT3 in cord blood specimens offers no advantage over present screening methods.


Thyroid stimulating antibodies in patients with subacute thyroiditis. A radioreceptor assay was used to measure thyroid stimulating antibodies (TSAb) during the acute and recovery phases in 7 patients with subacute thyroiditis. High levels of TSAb were detected in 4 patients during the acute phase. In two other patients, tests were borderline positive. In the latter two patients tests were negative by two weeks, whilst in the 4 patients with strongly positive tests initially, levels persisted for several weeks, falling to within the normal range by 3 months in the two patients in whom repeated tests were carried out. TSAb probably do not play a role in the transient hyperthyroidism commonly seen in this disorder, since the detection of TSAb did not correlate with clinical or biochemical evidence of hyperthyroidism. Thus, in this disorder, TSAb are apparently able to bind to thyroid membranes in vitro, but not stimulate the gland in vivo. On the other hand TSAb could possibly play a role in the recovery phase. The possible role of suppressor cells in the development of the transient immune abnormalities which are associated with temporary thyroid damage is discussed.


Dialysis dementia -- the Chicago experience. In the four years between 1972 and 1976 twenty out of 160 maintenance dialysis patients developed dialysis dementia. Their illness was characterized by an insidious onset of mental deterioration, speech disturbance, apraxia, and myoclonus. The disease progressed inexorably to a fatal outcome, the onset of seizures being an ominous sign, and the average duration of the illness being seven months. Routine biochemical studies were unremarkable, and osteodystrophy was not a prominent feature. Serial electroencephalograms (EEG) showed progressive slowing of the rhythm, usually antedating the neurologic symptoms. Brain scan and  flow studies were normal. Radio-iodinated serum albumin (RISA) scans in seven patients showed changes suggesting altered cerebrospinal fluid (CSF) dynamics. Treatment was generally ineffective, but ventriculo-peritoneal shunting produced transient neurologic improvement in one patient. Epidemiologic investigations showed high aluminum levels in city water during the period of the outbreak.


An outbreak of dialysis dementia due to aluminum in the dialysate. The dialysis dementia syndrome was observed in eight of 21  patients dialyzed in a small center during a 22-month period in which dialysate contained aluminum levels of 618 microgram/liter. This incidence of 38% was significantly higher than the zero incidence of four prior years when no aluminum was added to city water (p less than 0.05) and also when compared to the zero incidence in the 2.5 years subsequent to deionization of dialysis water which lowered its aluminum content to less than 1 microgram/liter (p less than 0.0002). Since other factors were not altered, we conclude that aluminum intoxication from the dialysate was the cause for the outbreak of this progressive encephalopathy.


Hyper/hypo-osmotic peritoneal dialysis.

Hyper/hypo-osmotic peritoneal dialysis. This report concerns the augmentation of peritoneal dialysis using alternating hyper/hypoosmotic peritoneal dialysates, and covers a detailed examination of the longest lived, anephric goat to be maintained using this delivery system. Experimental results show that with this technique: 1) urea clearance can be increased some 200% over control values, 2) the convective transport of urea is unimportant and the increased urea clearance is due primarily to increased peritoneal permeability, 3) net ultrafiltration and electrolyte balance can be easily controlled by variation of total electrolyte and glucose about an appropriate mean. A detailed autopsy failed to demonstrate any gross or microscopic pathology.


Locus of control and degree of compliance in hemodialysis patients. An experiment was conducted to test the hypothesis that dialysis patients with an internal locus of control orientation will show a higher rate of compliance to medication and dietary restrictions than those patients with an external locus of control. The results strongly supported the hypothesis. The possibility of interventions to modify patient locus of control is discussed, as is the use of this widely studied personality variable in predicting patient compliance.


Repetitive activity and Hopf bifurcation under point-stimulation for a simple FitzHugh-Naguma nerve conduction model. In response to point-stimulation with a constant current, a neuron may propagate a repetitive train of action potentials along its axon. For maintained repetitive activity, the current strength I must be, typically, neither too small nor too large. For I outside some range, time independent steady behavior is observed following a transient phase just after the current is applied. We present analytical results for a piecewise linear FitzHugh-Nagumo model for a point-stimulated (non-space-clamped) nerve which are consistent with this qualitative experimental picture. For each value of I there is a unique, spatially nonuniform, steady state solution. We show that this solution is stable except for an interval (I*, I(*)) of I values. Stability for I too small or too large corresponds to experiments with sub-threshold I or the excessive I which leads to 'nerve block'. For I = I*, I(*) we find Hopf bifurcation of spatially nonuniform, time periodic solutions. We conclude that (I*, I(*)) lies interior to the range of I values for repetitive activity. The values of I* and I(*) and their dependence on the model parameters are determined. Qualitative differences between results for the point-stimulated configuration and the space-clamped case are discussed.


Mating for schistosomes.

Mating for schistosomes. A mathematical model for schistosomiasis is developed under the hypothesis of promiscuous mating between mature schistosomes. The model is used to study epidemiology, control, and eradication of schistosome infections. Comparisons are made with previously published models that deal with monogamous mating and with parthenogenesis. We find that the two modes of mating give results that are essentially similar. On the other hand, essential differences exist between either mode of mating and the parthenogenetic case. Thus, we conclude that it is not of essential importance to find out if mature schistosomes are monogamous or promiscuous. A second conclusion is that the simplifying assumption of parthenogenetic egg-laying of schistosomes is not acceptable.


A stochastic locomotor control model for the nurse shark, Ginglymostoma cirratum. The locomotor behavior of the nurse shark (Ginglymostoma cirratum) is characterized by 17 variables (frequency and ratios of left, right, and total turns; their radians; straight paths (steps); distance travelled; and velocity) Within each of these variables there is an internal time dependency the structure of which was elaborated together with an improved statistical model predicting their behavior within 90% confidence limits. The model allows for the sensitive detection of subtle locomotor response to sensory stimulation as values of variables may exceed the established confidence limits within minutes after onset of the stimulus. The locomotor activity is well described by an autoregression time series model and can be predicted by only seven variables. Six of these form two independently operating clusters. The first one consists of: the number of right turns, the distance travelled and the mean velocity; the second one of: the mean size of right turns, of left turns, and of all turns. The same clustering is obtained independently by a cluster analysis of cross-sections of the seven time series. It is apparent that, among a total of 17 locomotor variables, seven behave as individually independent agents, presumably controlled by seven separate and independent centers. The output of each center can only be predicted by its own behavior. In spite of the individual of the seven variables, their internal structure is similar in important aspects which may result from control by a common command center. The shark locomotor model differs in important aspects from the previously constructed for the goldfish. The interdependence of the locomotor variables in both species may be related to the control mechanisms postulated by von Holst for the coordination of rhythmic fin movements in fishes. A locomotor control model for the nurse shark is proposed.


Stability of periodic travelling wave solutions of a nerve conduction equation. Nagumo's nerve conduction equation has travelling wave solutions of pulse type and periodic wave type. We consider the stability of the latter ones. We denote by L(c) the minimum spatial period of a periodic travelling wave solution whose propagation speed is c. It is shown that this travelling wave solution is unstable if L'(c) less than 0.


The permeability coefficient of the wall of a villous membrane. The equations hitherto used to correct the permeability coefficient for the unstirred layer influence are valid only for flat membranes. Therefore, appropriate equations for membranes with a villous surface (e.g., small intestine) have been derived. They take into account the non-linear concentration gradient in the intervillous part of the unstirred layer. Quantitative information about the geometry of the villous surface and the unstirred layer thickness are needed to calculate the permeability coefficient of the membrane wall (e.g., intestinal epithelium). The concentration of highly permeable substances drops sharply already in the upper part of intervillous space, so that the tips of the villi function as effective absorbing area. The intervillous concentration gradient of a substance with a low permeability coefficient is so small, that such a substance is absorbed by the total surface area of the villous membrane. The effective absorbing area of substances with intermediate permeability coefficient lies between the described limits.


Computer simulation of calcium-induced myotonia. In an extensive research project on myotonia, the ionic mechanisms which are at the basis of the phenomenon of calcium-induced myotonia have been taken into consideration. A mathematical model of a muscle fibre was constructed to demonstrate the possibility that anomalous values of the membrane permeability to Calcium ions have an active part in the genesis of myotonia.


A fully coupled transient excited state model for the sodium channel. II. Implications for action potential generation, threshold, repetitive firing, and accommodation. The axon membrane is simulated by standard Hodgkin-Huxley leakage and potassium channels plus a coupled transient excited state kinetic scheme for the sodium channel. This scheme for the sodium channel is as proposed previously by the author. Simulations are presented showing the form of the action potential, threshold behavior, accommodation, and repetitive firing. It is seen that the form of the individual action potential, its all-or-none nature, and its refractory period are well simulated by this model, as they are by the standard Hodgkin-Huxley model. However, the model differs markedly from the Hodgkin-Huxley model with respect to repetitive firing and accommodation to stimulating currents of slowly rising intensity, in ways that are shown to be related to those features of the sodium inactivation which are anomalous to the H-H model. The tendency for repetitive firing is highly dependent on that parameter which primarily determines the existence of the inactivation shift in voltage clamp experiments, in such a way that the more pronounced the inactivation shift, the less the tendency for repetitive firing. The tendency for accommodation is highly dependent on that parameter which primarily determines the 'tauc-tauh' separation, in such a way that the greater the separation the greater the tendency for the membrane to accommodate without firing action potentials to a slowly rising current.


Topological considerations in the theory of replication of DNA. An obvious difficulty of the Watson-Crick model of DNA is that the intertwining of the strands would seem to hinder their separation during replication. The nature of the difficulty is here made precise and is called the alignment problem. It is shown that the swivelase theory, found in current textbooks and thought to overcome the difficulty, does not in fact do so. The various conceivable solutions of the alignment problem are considered and rejected, leading to the conclusion that chromosomal DNA is not double-helical. An alternative model of DNA is discussed. In addition a topological classification of DNA denaturation processes is given, and an alternative interpretation of the gel electrophoresis experiments on circular duplex DNA is suggested.


An analysis of the mammalian ventricular action potential. A Hodgkin-Huxley model for ventricular excitation is abstracted from electrophysiological data. A singular perturbation analysis of the 8-dimensional phase portrait of the model characterizes the role of calcium during the plateau phase of the ventricular action potential and demonstrates how the calcium refractory period prevents tetanization.


Surveillance and follow-up of patients with implanted cardiac pacemaker by telephone transmission. A follow-up study on pacemaker function in 15 patients with implanted cardiac pacemaker has been performed by telephone transmission. The transmitting set consisting of electrocardiograph, pacemaker pulse modulator and acoustic coupler was manipulated by the patients themselves. ECG, pacemaker pulse, and pulse rate were simultaneously transmitted through 1 channel to the receiver in our clinic. Of 56 patients with pacemaker, 15 patients were surveyed by telephone transmission. In these patients battery exhaustion was detected in 3, competition in 2, and lead fracture in 1. The fact that surveillance and follow-up of the patients with implanted cardiac pacemaker could be carried out by telephone transmission as well as by clinic visitation tells us that the telephone transmission is a useful method and plays an important role in a pacemaker clinic. Moreover our study established its further usefulness in the patient's preference due to difficulties in travelling to the pacemaker clinic and in reducing patient's anxiety.


A study on the irregularity of the sequence of R-R intervals in chronic atrial fibrillation in man based on the time series analysis and the information theory. The mechanism of the irregularity of R-R intervals and especially the genesis of the long R-R intervals in atrial fibrillation were clarified. From the point of view of the present study, the sequence of successive R-R intervals can be regarded as a stochastic process, and consequently mathematical analyses can be applied, and the following conclusion could be obtained: the stability of the data, mathematically called stationarity, is present in the sequence of R-R intervals, and these intervals are independently and identically distributed. The probability density function is an Erlangian distribution with phase k of 20 to 26. Namely, as soon as, on the average, 20 to 26 atrial excitatory stimuli have arrived at the AV node, a threshold value of the AV node is reached and ventricular activation is induced. However, if we examine the mathematical structure of the sequence of successive R-R intervals in more detail, the following results can be evidently obtained: during atrial fibrillation with rapid ventricular response, the sequence of R-R intervals is completely independent, but with intermediate or slow ventricular response the adjacent R-R intervals correclate with each other and these adjacent intervals have at least the first order Markov property, which seems to be caused by the concealed conduction. Because of this Markow property due to the prolongation of the refractory period of the AV node, slow ventricular response results.


Sodium metabolism in essential hypertension. Natriuretic response to acute hypertonic saline load. In order to investigate the mechanism of the "exaggerated natriuresis" in hypertension, 300 ml of 3% saline was infused for 1 hour during hydropenia in 13 patients with normal renin essential hypertension and 5 normotensive subjects on a daily ingestion of 4 Gm and 16 Gm of NaCl. At the end of the infusion, the circulating blood volume indicated by the change in serum total protein concentration and the glomerular filtered load were increased in a similar manner in both groups. Prompt the enhanced natriuresis and diuresis were seen within 1--2 hours after starting the infusion in the hypertensives on a daily ingestion of 16 Gm of NaCl. Significant positive correlations were found between the change in mean arterial blood pressure (deltaMAP) and UV, and between deltaMAP and UNa V in the hypertensives either on a daily 4 Gm or 16 Gm ingestion of NaCl. Free water reabsorption (Tc H2O) was lower in the hypertensives than that in the controls at high levels of osmolar clearance (Cosm). Plasma renin activity (PRA) did not differ in either group on either NaCl ingestion and was equally suppressed on a daily ingestion of 4 Gm of NaCl, while little changed on a high salt intake. Plasma aldosterone levels changed in parallel with PRA. It is suggested that the "exaggerated natriuresis" is due to the decreased tubular sodium reabsorption, which may be the result of intrarenal hemodynamic changes related to the elevated renal perfusion pressure. The decreased medullary osmolar gradient probably induced by an increase in the medullary blood flow is a possible contributing factor in the enhanced sodium and water excretion, and the renin-aldosterone system does not seem to play an important role.


Effects of beta-adrenergic blocking drug pindolol (LB46) on cardiac fibers in relation to its membrane effects. Direct membrane effects and beta-adrenergic blocking action of pindolol were studied comparatively on isolated perfused cardiac fibers of dogs. In Purkinje fibers, the duration of transmembrane action potential decreased in concentrations higher than 0.5 mg/L. Maximum rate of depolarization also decreased in higher concentrations (5.0 mg/L or more). The functional refractory period decreased to a lesser degree compared with the decrease of the action potential duration. Nevertheless, slow-rising action potentials could not be abolished in premature responses, probably because of membrane depressant effects of this drug. In ventricular muscle fibers, these changes were minimum in the same range of concentrations. On the other hand, 0.05 mg/L of pindolol which was close to the therapeutic plasma concentrations and had no effect on action potentials of both Purkinje and ventricular muscle fibers, minimized the increase in automaticity of Purkinje fibers induced by 0.2 mg/L of isoproterenol. It is rationally speculated that the mechanism of antiarrhthmic action of pindolol is mainly due to its beta-adrenergic blocking action.


Direct positive chronotropic and inotropic effects of ouabain in the isolated and blood-perfused canine atrium. Using isolated, blood-perfused canine atrial preparations the effects of ouabain on sinus rate and contraction were investigated in 20 preparations. A continuous infusion of ouabain (1 microgram/min) usually induced a significant increase in sinus rate but occasionally a slight but no significant decrease followed by a clear increase, and then finally decrease followed by atrial arrest. On the inotropy, ouabain induced only distinct positive inotropic effect from the earlier stage, and the time to the maximum positive inotropic effect was much earlier than that to the maximum chronotropic effect. The positive chronotropic effect of norepinephrine was not affected by ouabain in the dose for inducing marked positive inotropic effect. On the other hand, the positive inotropic effect of norepinephrine was suppressed in percent changes by ouabain but not abolished. The negative chronotropic and inotropic effects of ACh were not significantly affected by ouabain in the dose for inducing marked positive inotropic effect. During atrial arrest by ouabain infusion, distinct staircase phenomenon disappeared. In this condition, atrial muscle responded more readily to higher frequencies of electric pacing (above 2 Hz) than to lower frequencies (under 1 Hz).


Increased vascular permeability of developing collateral arteries after femoral artery ligation in rabbits. Ligation of the main femoral artery is followed by a rapid development of collateral arteries. To detect an increase in vascular permeability of the collateral arteries, colloidal carbon (1 ml/Kg, iv) was injected into 153 rabbits at various times after ligation or sham-ligation of the main femoral artery. These animals were killed later and collateral arteries was dissected. Increase in vascular permeability was identified by the presence of visible carbon deposits on the vascular walls. The carbon deposits were frequently found on the intermediate segments of the collateral system in legs with ligation, but were not found on any arteries either in legs with sham-ligation or in contralateral untouched legs. The increase in vascular permeability was observed in 15 of 17 animals as early as 6 hours, in 32 of 36 animals 1 day but only in 5 of 21 animals 6 to 8 days after ligation. The arterial segments with carbon deposits showed various structural changes such as fragmentation of the internal elastic layer, degeneration of the medial muscle and deposition of fibrinoid material. These results indicate that vascular permeability transiently increases in the intermediate segments of developing collateral arteries. Acute vasodilatation may be responsible for the increase in vascular permeability.


Effect of verapamil on the transmural energy metabolism in the isoproterenol-induced myocardial lesion. The effect of verapamil on the isoproterenol (ISO)-induced transmural metabolic lesion in the left ventricular wall was investigated in the rat heart. The treatment with ISO 2.5 mg/Kg s.c. on 2 consecutive days resulted in significant decreases of creatine phosphate in the subendocardium (ENDO) and of adenosine triphosphate in the ENDO and the subepicardium. On the other hand, inorganic phosphate (Pi) and lactate (LA) were increased in both layers. These changes were more prominent in the ENDO. Pretreatment with verapamil 25 mg/Kg s.c. prevented the reduction of high energy phosphate compounds and the increases of Pi and LA in both layers by ISO.


Hemodynamic effects of the concomitant use of intra-aortic balloon pumping and venoarterial bypass without oxygenation in cardiogenic shock. The concomitant use of INTRA-AORTIC BALLOON PUMPING (IABP) and venoarterial bypass (VAB) without oxygenation (VABsO) was performed in 10 experiments using 6 dogs in cardiogenic shock. VABsO was accomplished with the cricuit from the right atrium to the femoral artery and bypass flow rates were set at approximately one third of the baseline cardiac output. Displacement volume of the IABP balloon was 10 or 20 ml. Evaluation of hemodynamic effects of the concomitant use was carried out, as compared with the single use of IABP or VABsO. The following findings were obtained: (1) In the concomitant use, left ventricular afterload decreased, while mean aortic root pressure increased. Increase in total perfusion flow, decrease in mean left atrial pressure and decrease in left ventricular stroke work were shown more effective than each of the single uses. (2) These results suggest that the concomitant use of IABP and VABsO can be used as a second step assisted circulation when IABP is shown uneffective in the case of severe cardiogenic shock.


Primary aldosteronism aggravated during peripartum period. Two cases are reported of a 30-year-old and of a 28-year-old Japanese women with primary aldosteronism in whom metabolic and blood pressure abnormalities were aggravated during peripartum period. The characteristic findings in 2 present cases are as follows; 1) lower blood pressure during pregnancy, 2) elevated blood pressure during peripartum period, and 3) after parturition, serum potassium decreased, and the blood pressure elevated. The reason why the hypertension and hypokalemia associated with primary aldosteronism were ameliorated during pregnancy was thought to be due to the increased secretion of progesterone. Furthermore, the rapid recurrence of symptoms, increase in blood pressure, and hypokalemia in the post-partum period could be related to elevated prolactin and decreased progesterone levels.


Ruptured sinus of Valsalva aneurysm into the left ventricle. A rare case of sinus of Valsalva aneurysm ruptured into the left ventricle was reported. The echocardiogram was suggestive of the diagnosis. The abnormal echo extended from the aortic root to the left ventricular cavity in diastole and disappeared in systole. Discussion was made on the etiology and differential diagnosis.


Final localization of Schistosoma japonicum in the lungs of field rats, Rattus mindanensis, in Leyte, Philippines. Among 45 specimens of Rattus mindanensis (Hearns, 1,905) caught in an endemic area of schistosomiasis japonica in Leyte, Philippines, 39 (86%) were found to be positive for Schistosoma japonicum. Lung examination of 24 autopsied rats revealed a high incidence of pulmonary infection and the flukes were found in 20 rats (83%). In 24 (73%) out of 33 rats, the flukes were seen in the hepatic portal vein. Only 29% of the rats were positive for Schistosoma ova in the intestinal wall. The average number of living worms was much greater in the lungs (19.2) than in the liver (12.4). However, fewer fully developed worms of oviposition stage were found in the lungs than in the liver. In the lungs widespread and massive nodules containing living worms and distinct lesions due to embolism were observed histopathologically.


An analysis of the fatty acid composition of total lipids from mycoplasmas. The fatty acid composition of the total lipids obtained from 9 species (22 strains) of Mycoplasma and 3 species (7 strains) of Acholeplasma was determined by gas-liquid chromatography (GLC). The major fatty acids of the Mycoplasma species were palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1), and linoleic acid (C18:2). Lauric acid (C12:0) and myristic acid (C14:0) were present in small amounts in this genus. For the Mycoplasma species, the most prevalent fatty acid was C16:0 or C14:0, and other leading fatty acids were C12:0, C18:0, C18:1 and C18:2. A substantial amount of C12:0 and C14:0 was found in the Acholeplasma species. It was confirmed that C12:0 and C14:0 were synthesized de novo, based on the fact that 14C-acetate was incorporated into these acids. The total percentage of C16 fatty acid was less than that of C18 fatty acids in all the strains of Mycoplasma and Acholeplasma except 4 strains. This may be related to osmo-regulation of the L-forms of Streptococci as mentioned in other reports.


[Studies on predilection area of gastric ulcer viewed from healing process of experimental gastric ulcers (author's transl)]. Clinically, it is true that gastric ulcer is more common along the lesser curvature and less common along the greater curvature. To elucidate this difference in ulcerognesis, two experimental ulcers were prepared in dogs at the sites, one at the angular incisure and the other at the corresponding greater curvature after the method by Hatafuku & Thal. The fates of these ulcers studied endoscopically, macroscopically, histologically and with the use of microangiography. The results obtained are summarized as follows. 1) When two ulcers only were prepared, better healing was consistent for the greater curve ulcer. 2) Experimental ulcers with simultaneous ligation of gastric vessels resulted in poor healing of both ulcers, though the greater curve ulcer showed better healing than the lesser curve ulcer. 3) Endoscopically, dogs with vessel ligation showed antral congestion and edema. These findings, however, disappeared in 3 to 4 weeks. 4) Histamine injection accelerated the rate of early perforation and both experimental ulcers showed no tendency of healing. In conclusion, delayed healing was almost consistent for the lesser curve ulcer under various conditions. The cause for this may be explained by the increased motility with repeated ischemic condition at the lesser curvature.


[Studies on predilection area of gastric ulcer viewed from gastric motility (author's transl)]. Clinically, most gastric ulcers are located in the region of the incisura angularis, but they are least found along the greater curvature. To elucidate this difference, following experiments were carried out. A total of 22 mongrel dogs were used. A set of bipolar electrodes and/or a water-proof strain gage were chronically implanted at both the incisura and the corresponding site of the greater curvature. Electrical and contractile activities of these two sites were compared at the fasted state and under the stimulations by food, neostigmine and tetragastrin. Results are summarized as follows. 1. Electromyographically, the propagation velocity was always greater along the greater curvature than the lesser curvature. The discharge interval of BER and incidence of antiperistalsis were identical for both the lesser and greater curvature. 2. Through the course before and after the stimulation, there was no difference in the frequency of contraction waves, while the amplitude and motility index of the contraction were definitely greater at the incisura than the corresponding greater curvature. In conclusion, the present study revealed that the contractile force of the incisura was always greater than that of the corresponding greater curvature. It is possible that the peristaltic contraction could cause stronger repetitive ischemic condition of the incisura than the corresponding greater curvature. It is estimated that the gastric motility is one of the important factors for the predilection or delayed healing of gastric ulcers seen in the region of the incisura angularis.


[Experimental and clinical studies on anti-reflux effect of modified end-to-side esophagogastrostomy in proximal gastrectomy (author's transl)]. A modified end-to-side esophagogastrostomy devised at our department to prevent postoperative reflux was evaluated both experimentally in 15 dogs and clinically in 4 cases. The seromuscular coat of the anterior wall of the remnant stomach was excised longitudinally, the distal esophagus was buried and anastomosed at its distal end so as to provide an effective thin flap valve. The presence of gastroesophageal reflux was attested by the use of withdrawal pH, intraluminal pressure and fluoroscopy studies as well as by autopsy in dogs. Furthermore, 7 out of 15 dogs were subjected to the analytical study of reflux prevention mechanism employing an intraoperative pressure measurement. The results are summarized as follows: Gastroesophageal reflux was absent in 11 out of 15 dogs and in all the 4 clinical cases. A specific finding after this procedure was that even after resection of the cardia, there was seen creation of an artificial high pressure zone at the site of the anastomosis serving as a barrier to reflux. Reflux prevention mechanism of the present method lies in an effective flap valve mechanism which seals the distal esophagus receiving the side pressure from the artificial fundus. The procedure is technically easy and seems to serve overcoming the problem of postoperative reflux highly seen after conventional end-to-end or end-to-side esophagogastrostomy.


[Effects of selective proximal and truncal vagotomy on canine gastric motility (author's transl)]. With the use of electromyography and intraluminal pressure recording of the pylorus, the effect of selective proximal and truncal vagotomy on the gastric motility was investigated in 10 dogs. The results are summarized as follows: 1. Control dogs showed regular discharge intervals with elevation of intrapyloric pressure coinciding with the action potentials. There was seen no occurrence of antiperistalsis. 2. Selective proximal vagotomy resulted in the prolongation of discharge intervals along with slight decrease in the incidence of action potentials. The rate of antiperistalsis was 4.4%. Besides, the rate of pyloric contraction also showed a tendency of slight decrease. 3. Truncal vagotomy lead to the prolongation of discharge intervals and decrease in the incidence of action potentials, though these changes were milder than those after selective proximal vagotomy. The incidence of antiperistalsis was 6.8% which was higher than the one after selective proximal vagotomy. Eelvation of intrapyloric pressure did not necessarily took place coinciding with the action potentials. Intrapyloric pressure as well as the incidence of pyloric contraction showed a marked decrease when compared with those of the control and selective proximal vagotomy dogs. Out of these results, it is concluded that the selective proximal vagotomy is superior to the truncal vagotomy when viewed from the preservation of the gastric motility.


Localization of glutamine accumulation and tubular reabsorption in rat nephron. Glutamine accumulation in rat kidney was investigated by giving large loads of gluta, mate and aspartate and measuring glutamine changes in seven completely defined portions of the nephron and in small patches from the thin limb area and from the papilla. Both glutamate and aspartate (which is partly coverted to glutamate) caused increases up to sixfold in glutamine which were mainly confined to the proximal straight tubule. Plasma glutamine is minimally affected. In contrast, large glutamine loads doubled plasma glutamine and caused about a doubling of glutamine concentrations in all parts of the nephron, but resulted in no greater change in the proximal straight tubule than elsewhere. Simultaneous inulin and glutamine measurements make it seem likely that the proximal convoluted tubule is a major site of glutamine reabsorption. The low glutamine concentrations in these cells (only 40% higher than that in plasma) indicate a very small gradient at the antiluminal surface. We suggest that the proximal straight tubule is the major site of glutamine synthesis but that it may not be an important site of glutamine breakdown.


Some hemodynamic determinants of immune complex trapping by the kidney. This study was undertaken to help clarify the relationship between capillary hemodynamic events and the tissue uptake of circulating immune complexes (IC). In each of 23 dogs, bovine serum albumin (BSA) and rabbit antiBSA soluble IC labeled with 125I were given by constant i.v. infusion, and IC uptake by a normally perfused kidney was compared to that of the contralateral kidney in which renal blood flow (RBF) was changed by renal artery constriction or raised ureteral pressure. In these same animals, IC uptake in 15 other major organ systems was also measured simultaneously. During IC infusion microspheres of 85Sr were injected to measure cardiac output and tissue blood flow, and red cells labeled with 51Cr were infused to mark tissue vascular volume. At completion of the IC infusion, tissue samples were taken from the kidneys and the 15 other major organs systems. From the isotope content of each tissue, we determined IC content, blood flow rate, vascular transit time, and fractional uptake of IC (FIC). In addition, glomeruli were isolated from renal cortex to assess IC uptake in glomerular versus renal nonglomerular tissue. We found that 1) for kidney, IC delivery rate, capillary hydrostatic pressure, and capillary ultrafiltration rate are less important than the plasma IC concentration in determining IC uptake; 2) for each organ studied, the principal determinant of IC uptake per gram of tissue, at any given PIC, is vascular volume per gram of tissue; 3) tissue vascular volume per gram of tissue may determine IC uptake per gram of tissue because tissue vascular volume determines the capillary surface area in contact with circulating IC or because tissue vascular volume determines tissue vascular transit time, at any given tissue blood flow rate.


Renal sodium retention during volume expansion in experimental nephrotic syndrome. We have studied sodium retention during volume expansion in rats with autologous immune complex nephropathy (AICN), a model of nephrotic syndrome (NS) in which GFR after volume expansion was not different from that in adjuvant-injected controls (C). AICN rats developed heavy proteinuria (298 +/- 27 vs. less than 10 mg/day), hypoalbuminemia (2.14 +/- 0.15 vs. 3.08 +/- 0.12 g/100 ml) and hypercholesterolemia (181 +/- 22 vs. 58 +/- 4 mg/100 ml). After saline, there were no significant differences in blood pressure (119 +/- 2 vs. 114 +/- 2 mm Hg), renal plasma flow (4.9 +/- 0.41 vs. 4.1 +/- 0.28 ml/min), inulin clearance (1.37 +/- 0.06 vs. 1.55 +/- 0.10 ml/min), or SNGFR (47 +/- 2 vs. 53 +/- 4 nl/min). Sodium excretion, however, was significantly lower in NS rats (4.7 +/- 1.1 vs. 9.2 +/- 1.2 muEq/min). Proximal sodium reabsorption was decreased in NS rats (35 +/- 2 vs. 41 +/- 2%, 2.5 +/- 0.2 vs. 3.3 +/- 0.2 nEq/min). Sodium delivery into the loop, however, was equal in NS and C, since the slightly lower filtered load in NS rats offset the depression in proximal reabsorption. Sodium reabsorption by the loop and by the distal convoluted tubules were equal in NS and C. Thus, sodium delivered into the cortical collecting ducts was the same in both groups (0.33 +/- 0.17 vs. 0.34 +/- 0.07 nEq/min; 4.5 +/- 0.6% of filtered sodium vs. 4.4 +/- 0.3%). The percent of filtered sodium excreted in the urine, however, was significantly lower in the NS rats, 2.18 +/- 0.48% vs. 4.0 +/- 0.58%. We conclude that antinatriuresis in this model of NS is determined beyond the superficial late distal convoluted tubule. The inability to excrete the sodium load during volume expansion is due to either enhanced reabsorption by the collecting duct or to abnormal function in deep nephrons.


Nitrogen balance during intermittent dialysis therapy of uremia. Daily measurements of nitrogen balance were made at two levels of protein intake in five patients undergoing chronic intermittent dialysis therapy. During ingestion of high (1.4 g/kg of body wt) protein intake, nitrogen balance was positive on nondialysis days and negative on dialysis days, so that cumulative balance for the week of study was not different from zero. During ingestion of low (0.5 g/kg) protein intake, nitrogen balance was approximately zero on nondialysis days but was again negative on dialysis days, so that cumulative balance for this period was negative. The negative nitrogen balance observed on dialysis days was associated with a higher rate of urea nitrogen generation (Gu, g/24 hr, determined by a kinetic model of urea nitrogen in dialysis patients) that was most evident in the hours immediately following dialysis. Net protein catabolic rate (PCR, g/24 hr), derived from total nitrogen mass balance equations, correlated very closely with Gu:Gu = 0.154 PCR - 1.7, r = 0.96. This relationship agreed well with previous observations made in nondialyzed uremic patients under more steady-state conditions. These studies demonstrate that nitrogen balance is negative on dialysis days regardless of protein intake, and that Gu is higher on dialysis days. The negative nitrogen balance could result from amino acid loss in dialysate and from increased protein catabolism stimulated by loss of glucose into dialysate.


Evidence of an autologous immune complex pathogenic mechanism in acute poststreptococcal glomerulonephritis. Clinical and experimental studies have suggested a role for antiimmunoglobulins in the pathogenesis of glomerulonephritis associated with streptococcal infection. We attempted to localize anti-IgG in the kidneys of 22 patients who had renal biopsies performed 7 to 66 days after the onset of acute poststreptococcal glomerulonephritis (APSGN). In addition to routine localization of immunoglobulins and C3, specimens were stained with neuraminidase-treated, heat-aggregated, and unmodified IgG. Twelve biopsies showed staining with fluorescein-labeled human neuraminidase-treated IgG. A lesser number gave positive staining with the other IgG preparations. Following treatment of slides with 0.01 M citrate buffer, seven previously negative biopsies showed positive staining with neuraminidase-treated IgG. The demonstration of anti-IgG by these methods was possible in 19 out of 22 biopsies. It correlated best with the presence of C3 and IgG, and to a lesser extent with IgM, in the renal glomerulus. These results and our previous finding of elevated levels of serum anti-IgG early in the course of APSGN, and as early as 8 days following the antecedent streptococcal infection, support a role for anti-IgG in the immune pathogenesis of APSGN. Although our series of studies support the hypothesis that anti-IgG is formed to an IgG modified enzymatically by streptococcal product, the formation of this autoantibody to IgG incorporated in an exogenous (streptococcal antigen-antibody) complex can not be ruled out.


Nonprogressive, histologically mild membranous glomerulonephritis appearing in all evolutionary phases as histologically "early" membranous glomerulonephritis. Seven adult patients with idiopathic nephrotic syndrome and with a glomerular histology considered normal but with ultrastructurally provable membranous glomerulonephritis (MNG) were studied. The glomerular lesions were found to represent all ultrastructural evolutionary phases (A,B, and C) of MGN. In patients with serial biopsies, the membranous lesion seemed to have passed through all of its evolutionary phases towards healing (C) without developing spikes or thickening of the glomerular basement membrane (GBM), i.e., the traditional light microscopic characteristics of MGN. This evolution was associated with a benign clinical course. The membranous lesions were associated with a vacuolization visible in obliquely or tangentially cut segments of the GBM in silver-stained paraffin sections. This alteration seemed to be created by irregularities of the argyrophilic lamina densa of the GBM and not by subepithelial deposits, as suggested previously. All seven patients had a remission of the nephrotic syndrome which appeared to be spontaneous and not drug-induced. The amount of proteinuria correlated with the ultrastructural phase of MGN and with the intensity of immunofluorescent staining. In one patient, the latter became negative.


[The clinical course of an embolism of a branch of the retinal artery (author's transl)]. The way in which a varying amount  of blood runs past an almost obliterating yellowish-grey, homogenous "embolus" in a branch of the artery is shown. Finally although the "embolus" remained, there was an almost normal blood flow in amount. Retinal arteries running downwards showed changing vascular spasms, sometimes at the origin, sometimes further away from the central artery. This produces reversible scotomas. A small artery running nasally is sometimes better and sometimes worse supplied with blood. Temporary and permanent scotomata develop. Haemorrhages appearing here vary in extent.


[An error in the fluorescence angiographic diagnosis of a subretinal process (author's transl)]. A presentation is given of a malignant melanoma of the choroid of a 15-year-old girl. The tumor was erroneously considered as to be a subretinal hemorrhage produced by a choroidal rupture after an accident. A beginning melanosis bulbi resulted in the enucleation and the histological examination of the eye, which confirmed malignant melanoma of the choroid.


[On the distribution of the values of intra-ocular pressure in the normal population (author's transl)]. The distribution of applanation intraocular pressure was studied in a normal population over a period of 7 years. The distribution shows a bimodal curve with peaks at 13 and 17 mm. The assumption is made of two populations whose pressures are symmetrically distributed. Some genetic and clinical aspects of these findings are discussed.


[Glaucoma in the presence of chalcosis (author's transl)]. There are only few reports in the literature about the coincidence of a glaucoma with a chalcosis. After briefly presenting such a case the authors discuss the differential diagnosis; a strictly monocular chronic simple glaucoma, a contusion glaucoma or a glaucoma secondary to chalcosis. Since glaucoma and chalcosis coincide so infrequently there is no basis for assuming a true secondary glaucoma due to chalcosis existing, as is the case with siderosis.


[On the differential diagnosis of inflammatory illness of the orbit. Computer tomographic results (author's transl)]. Selectet CT-findings in inflammatory orbital diseases are demonstrated with special regard to the differential diagnostic importance of details. Based on the criteria-density of retrobulbar fat, swelling of extraocular muscles, dilatation of orbital vessels, representation of osseous borders of the orbit, pneumatisation of paranasal sinuses etc-typical CT-patterns of disease entities are demonstrated. The differentiation of inflammatory diseases, orbital tumors, and vascular disorders is discussed. The limits of diagnostic interpretation are pointed out.


[Light-and electron microscopic appearances of the orbicularis oculi muscle in patients with chronic progressive ocular muscular dystrophy and in normal persons (author's transl)]. In 8 patients with chronic progressive ocular muscular dystrophy, of whom some showed a weakness of lid closure, and in 3 normal persons (aged 62 to 69 years) biopsies of the orbicularis oculi muscle were investigated with the light- and electron microscopes. We tried to find out if the histopathological investigation alone of the orbicularis oculi muscle can establish the diagnosis of ocular muscular dystrophy or not. Both groups of investigated persons showed myopathic changes in the orbicularis oculi muscle. These changes were explained as followings of catabiosis (so called "secondary myopathic reaction") in the normal persons. The changes of the patients with myopathies, however, were explained as primarily myopathic, especially with regard to the anomalies of structure, and the pathological inclusions of the mitochondria. The findings showed that there occurred similar histopathological phenomena seen by light microscope in both groups of investigated persons; the muscle cell changes of the myopathy patients, however, were more prominent in the examination of the ultrastructure.


[Severe microphthalmus with Patau's syndrome (author's transl)]. The authors describe a new-born child with Patau's syndrome in which D-trisomy was zytogenetically proved. The interest in this case is justified by the fact that an anophthalmos was suspected on clinical examination, but the histological examination showed a severe grade of bulb hypoplasia. The authors stress the significance of chromosome examination in cases of multiple congenital deformities associated with eye changes.


[The influence of local anesthetics on corneal epithelium. A scanning electron microscopic study (author's transl)]. The effect of different local anesthetics (Cocain 4%, Lidocaine 2%, Proparacain) on the corneal epithelium in rabbits was examined under scanning electron microscope. The experiment was divided into three groups. Group 1 received one application of two drops of the given local anesthetic for a reaction time of 5 minutes. Group 2 received two drops of the given anesthetic after 0, 5 and 10 minutes. The cornea was excised after 15 minutes. Group 3 were measured after a single application of Proparacain using a Schiötz or hand applanation tonometer according to Draeger. After a single dose of a local anesthetic principally the same changes in the surface of the cornea were observed with all the preparations used: a distinct decrease in the number of microvilli and microplicae, disruption of the intercellular spaces and the prominence of the cell nuclei which under normal conditions are not visible. After several applications the greater toxicity of Cocain compared with the other preparations was clearly seen through the disruption of the plasma membrane and the cytoplasm. The damage effected several layers of cells. Tonometry when correctly performed causes no additional damage to the cell surface.- The effect of local anesthetics on the cell membrane can only take place after the disruption of the tear film. The results emphasize that local anesthetics should only be applied when absolutely essential.


[Experimental investigations concerning a topical application of sisomicin in the eye (author's transl)]. Sisomicin is a new aminoglycoside, which sometimes is active against bacterial isolates resistant to other antibiotics of this group. The compatibility of sisomicin and its penetration into the different tissues of the eye were studied in rabbits. The substance was well tolerated, when applied as drops or injected subconjunctivally. Concentrations of sisomicin which are effective against most bacteria were found in the cornea and in the aqueous humour, but it did not penetrate into the vitreous body.


[Autophagy in visual cell renewal processes (author's transl)]. The biological significance of autophagy in the metabolism of visual cells is discussed. In the process of autophagy, parts of the cytoplasm including cell organelles are surrounded by membranes. This formation is called an autophagic vacuole. Then, the contents of the vacuole are degraded by enzymes. Autophagy is a well known phenomenon occuring in various tissues. In visual cells, however, it was only recently first described by Remé and Young and Remé. Autophagy has been shown to occur in the visual cells of several normal species. The amount of autophagic activity follows a 24-hour rhythm, complementary to an overall protein synthesis. Thus, within a 24-hour period, one cycle of formation and degradation in visual cells is completed. Incubation of isolated retinas significantly increases the number of autophagic vacuoles in inner segments, indicating an adaptation of visual cells to changed metabolic conditions. It is assumed that changes in normal autophagic turnover may be an important factor in visual cell degenerative diseases, thus opening up a new field in retinal pathology.


[Advantages of Ocusert treatment (author's transl)]. The medical service of Deutsche Bundesbahn supervises through its eye-doctors all those employees who, affected to glaucoma caused by shift and stress, are rated approximately 170 per year. The drug carrier Ocusert (Federal Republic of Germany: Chemie Grünenthal) which is applied on most of the glaucomas is discussed-especially with regard to social-medical aspects.


[Clinical tests on the use of ethoxzolamide in glaucoma therapy (author's transl)]. Ethoxzolamide is a potent carboxyanhydrase inhibitor, and its use in chronic glaucoma and in the acute glaucoma attack is described in the present investigation. Ethoxzolamide shows itself to be extremely well tolerated. The frequency and intensity of the side-effects is low. The electrolyte balance remains also after prolonged administration compensated. The important advantage of this drug is its low dosability. Ethoxzolamide, which was already 1958 clinically evaluated (Gordon-Posner), represents a valuable medication for conservative glaucoma therapy.


[Treatment results with weak concentrations of pilocarpine in patients with primary glaucoma (Spersacarpin 0.25%) (author's transl)]. 25 Patients suffering from simple chronic glaucoma were treated with a 0.25% Spersacarpin solution. The intraocular tension was normalised in 22 Patients; only in 3 was it necessary to use stronger concentrations. The Spersacarpin 0.25% solution, which has a strong hypotensive and myotic effect but hardly any myopia inducing action, was well tolerated by all patients.


[On the conservation of the tear ducts in tumor surgery in the eyelid region (author's transl)]. The conservation of the tear ducts, as well as their partial conservation, must be considered when operating on smaller tumors, depending on the clinical picture and the histological aspect. However, the preparation should be done under magnification to facilitate delineation of the borders of the tumor and to immediately recognize when the tear ducts are opened. The histological description of the kind of tumor and the answer to the question of excision into the healthy tissue decide the further procedure. The placing of an indwelling tear duct probe in the form of a supramid thread or of a polyethylene tube has proved favorable. In case partial resection of the peripheral parts of the canal system is necessary, the remains of the posterior wall of the vertical or horizontal part of the canaliculus must be opened with Vanna's scissors. The remaining vertical or horizontal part of the canaliculus does not lose its suctionpressure pump capillarity when it is opened, but ensures tear drainage.


[Results of research on the microflora of the conjunctiva with either chemotherapeutically pretreated eyes or eyes not influenced by drugs concerning the question of the preoperative prophylaxis against infections (author's transl)]. In this study the results of 396 smears of conjunctiva are analysed concerning the microflora of chemotherapeutically pretreated eyes in comparison with eyes not treated. The results of microbiological culture indicate only a small statistically unsignificant difference in regard to the quantitity of sterile smears as well as the distribution of bacteria of both research groups. The discussion is on the question of unaimed preoperative prophylaxis of infection as conditio sine qua non before intraocular procedures on eyes free of phlogistic irritation.


[An unusual form of cogwheel macula degeneration: central and paramacular alveolar pigment epitheliopathy (author's transl)]. A peculiar and rare form of spoke-like macular lesion is described as found bilaterally in a 53 year old woman. The unmistakable ophthalmoscopic and angiographic findings are also discussed. Although the clinical picture can be explained by a pigment epitheliopathy with secondary involvement of the neuroepithelium, the precise etiology of this fundus disease still remains problematic.


[Conjunctival alterations by sympathomimetic drugs (author's transl)]. This is the report of two patients, who used eye drops containing adrenergic agents for a relatively long period of time because of conjunctival troubles. The eye drops contained phenylephrine or tetryzoline or naphazoline. As a consequence of the vasoconstriction, the treatment led to an epithelial xerosis in the region of the caruncula and of the neighbouring eyelid edges. The keratinisation resulted in a closure and disappearance of the puncta lacrimalia. Therefore, the application of vasoconstrictive eye drops for a longer period of time is discouraged. Moreover, eye drops with a low concentration of the sympathomimetic agent should be preferred.


[Intensive transillumination and spot-lighting with a new fiber optic light source (author's transl)]. An equipment for intensive transillumination is described which is able to provide approximate 8 fould higher angular emittance and 2.5 fould higher flux compared with customary used tools. The diameter of the fiber optic is about 1 mm and the angle of emittance of 30 or 60 degrees can be chosen. Even the experimental use of fiber optic with smaller diameter for intravitreal illumination has shown higher light intensity compared with other available light sources.


Experimental Coxiella burnetii infection of guinea pigs and mice. The susceptibility of five inbred strains of mice, designated DBA/1J, DBA/2J, C57BL/6J, Balf/CJ, and AKR/J, as well as outbred Hartley and Moen-Chase guinea pigs to infection with Coxiella burnetii by several routes was studied. The DBA/2J mice were more susceptible to infection and had higher mortality rates than other strains of mice. Guinea pigs were more susceptible to infection than mice. Lesions observed in the infected animals were similar to those previously described in man and experimentally infected animals.


Preliminary report on the magnesium deficient rat as a model of epilepsy. Weanling male rats fed a low magnesium diet for 14 days were protected from audiogenic seizures by administration of phenobarbital and diphenylhydantoin. Amphetamine, levo-dopa, and magnesium chloride injected 45 minutes prior to testing did not prevent the seizures. In contrast to weanling male rats which became mortally seizure prone, 3--5 week-old female rats fed a low magnesium diet for 17--21 days varied as to their susceptibility to audiogenic seizures. If thrown into seizures by a loud noise, the females frequently could be revived for subsequent testing, thus affording the opportunity to design experiments using fewer animals.


Prevention of cervical lymphadenitis in guinea pigs by vaccination. Cervical lymphadenitis, caused by beta hemolytic Streptococcus of Lancefield's group C, was experimentally produced in guinea pigs. Experimental transmission of cervical lymphadenitis was successful when a scratch in the oral mucous membrane was inoculated with a strain of the causative organism which had been isolated during an epizootic of cervical lymphadenitis. Animals without a mouth lesion did not develop the disease when inoculated in the same manner. Another strain, obtained from the American Type Culture Collection (ATCC-12960) was also used. This latter strain was found to have a low degree of pathogenicity for guinea pigs, and it was used for immunization experiments. Seventy-nine percent of animals inoculated orally with strain 12960 withstood later challenge with the virulent strain, whereas only 5% of the controls withstood the same challenge.


Characterization of Pasteurella multocida isolates from the nares of healthy rabbits with pneumonia. Pasteurella multocida was isolated from 42 of the 135 (31%) deep nasal swabs from clinically healthy conventional rabbits supplied by two vendors. The prevalences were significantly different among sex, age, and sources. The females and adults had higher prevalences when compared to males and juveniles, respectively. One vendor's rabbits had a prevalence of 41% while the other had 20%. Biochemically, only 24% of the 42 isolates decarboxylated L-ornithine, and 55% produced indol. All isolates were sensitive in vitro to several of the commonly used antibiotics, but most isolates were resistant to lincomycin, streptomycin, and sulfonamides. Typing with a hyaluronidase inhibition test revealed that 28 of the 42 (67%) isolates were type A. Type A was the major type isolate, whether the samples came from healthy rabbits or from rabbits with pyogenic lesions. The acriflavine flocculation test showed that two of the 42 (5%) isolates were type D. Although none of the 42 isolates were positive to both hyalurondase and acriflavine tests, 12 of the 42 (29%) isolates were negative to both tests, indicating that these isolates were not typeable by these two methods. The demonstration of more than one capsular type of Pasteurella multocida in rabbits indicates the need for more extensive studies on this important rabbit pathogen.


Decrease in the lethal effect of snake venom by serum of the opossum, Didelphis marsupialis. Decrease in the lethal effect of several crotalid snake venoms were compared when diluted or mixed with opossum serum, normal horse serum, or normal dog serum and injected into mice. Normal dog and horse serum showed no protective qualities while opossum serum and diluted antivenin were approximately equivalent in their protective effect.


Hepatic jaundice in a colony of nude mice. A colony of nude mice was maintained under controlled standards of care for 12 months, at which time a rapidly escalating liver disease developed in the animals, characterized by jaundice, emaciation, and rapid death. Histologically, the livers had swollen, vacuolated hepatic cells and increased numbers of enlarged Kupffer cells. Mouse hepatitis virus was not isolated from the livers of sick mice. Although the nature of the lesions suggested toxicity, efforts to reproduce the lesions by increased exposure to chemical compounds used for colony husbandry were unsuccessful. A definitive determination of the causative agent was not made.


A simple method for extending the period of surgical anesthesia in rats. The period of surgical anesthesia induced in a laboratory rat by the recommended intraperitoneal dose of pentobarbital may be extended fourfold by the oral administration of a second dose of pentobarbital diluted with water.


An outbreak of cecal mucosal hyperplasia in hamsters. Cecal mucosal hyperplasia associated with diarrhea, runting, and high mortality in suckling and weanling hamsters occurred as a natural disease outbreak in a production colony. Young hamsters were runted, and their perineal hair was stained and matted with liquid feces. Their ceca were thickened, contracted, congested, and had scant luminal content. There were severe hyperplasia of cecal crypts, accompanied by increased mitotic activity, inflammation, and focal mucosal erosion. A variety of bacteria was isolated, but none was considered pathogenic. No relationship of cecal hyperplasia to transmissible ileal hyperplasia of hamsters was found. Hyperimmune serum from hamsters with transmissible ileal hyperplasia did not react by immunofluorescence against hyperplastic cecal mucosa. Electron microscopy did not reveal a caustive agent. Transmission attempts have been unsuccessful. Cecal mucosal hyperplasia is apparently a newly discovered disease entity in hamsters with the clinical sign of diarrhea.


Fiberoptic esophagogastroscopy, brushings, and biopsy in rabbits (Oryctolagus cuniculus). The esophagus and stomach of rabbits were examined with a pediatric fiberoptic endoscope. The procedure involved general anesthesia and placement of an endotracheal airway followed by endoscopy. Photography, biopsies, and brushings for histology, cytology, and microbiological cultures were accomplished using this procedure. Rabbits were endoscoped and brushed repetitively on successive days without inducing esophagitis.


Intravenous cannulation of hens for long-term infusion. Intravenous cannulation was performed on the brachial vein of the hen. The cannulation system consisted of a jacket that fitted around the body of the hen. An external sheath passed through the top of the cage, over a small pulley and was counter-weighted with lead. A subcutaneous polyethylene sheath was extended from the wing near the site of cannulation to the mid-point of the back between the wings and into the external sheath. Once the polyethylene cannula was inserted into and attached to the brachial vein, the free end was passed through the subcutaneous sheath, into and through the external sheath, and attached to a syringe or pump. No special post-cannulation care was necessary. The hens were housed in wire cages and received feed and water ad libitum. Twenty-four hens were continuously or intermittently infused for up to 73 days after cannulation.


Intracellular compartmentation and transport of metabolites. The intracellular locations of enzymes and metabolites were determined for ornithine metabolism in Neurospora. Pulse label experiments were used to measure the rates of intracellular translocations and the sizes of compartmented pools of metabolites in the mitochondrial, cytosolic and vesicular compartments. The results indicate that rapid equilibration occurs between these pools during growth in minimal medium, although the vast majority of the ornithine is confined to the vesicular compartment. Arginine, the biosynthetic end-product of ornithine metabolism, regulates ornithine utilization through a combination of feedback inhibition, repression, and control of intracellular translocations. The last phenomenon plays a decisive role indicating that the regulation of intercompartmental translocations may be a common mechanism in rapid adaptation responses in eukaryotic cells.


Increase in the affinity of the uridine phosphorylation system for ATP after serum or insulin activation of 3T3 fibroblasts. The stimulation of uridine uptake, brought about by the addition of serum or insulin to quiescent 3T3 fibroblasts, is associated in the half-saturation concentration of the uridine phosphorylating system for the substrate ATP, with relatively little change in the maximum uptake or in the affinity for uridine. In stimulated cells the Km towards ATP fell in the range 0.053--0.187 mM, while V max was 34 to 52 pmoles/10(6) cells/min. In quiescent cells these values were 2.89--4.22 mM and 74.5--126 pmoles/10(6) cells/min, respectively. No difference was found, however, between the Km's for ATP when phosphorylation of uridine was determined using cell-free extracts prepared from either quiescent cells or from stimulated cells.


Steroid hormone receptor characterization of several histologic variants of a rat prostatic adenocarcinoma. Several histologic variants of the transplantable R-3327 prostatic adenocarcinoma carried in male Copenhagen rats have been characterized and the histologic types have been correlated with steroid hormone receptor content. One type is clearly an adenocarcinoma; this tumor is hormonally responsive and contains substantial amounts of both androgen and estrogen receptors. In contrast, another histologic type, a fibrosarcoma, is hormonally nonresponsive and does not contain either receptor. A third histologic variant is classified as a carcinosarcoma and contains histological elements of both adenocarcinoma and fibrosarcoma and is also hormonally responsive. This tumor contains lower receptor levels than the adenocarcinomas but more than the fibrosarcomas. The androgen receptor appears to be identical in the different histologic forms of the tumor: the sedimentation coefficient is 7.8S and the dissociatiln constant for methyltrienolone is 4 x 10(-9) M. Similarly, the estrogen receptor from the different histologic forms of the tumor has a sedimentation coefficient of 8.3S and the dissociation constant for estradiol is 7 x 10(-10) M. These findings clearly distinguish the cytosol binding macromolecules from plasma binding proteins, and classify them as steroid hormone receptors. Further, rat serum was devoid of androgen and estrogen binding in the 8S region. Normal prostate tissue from Copenhagen rats contained low levels of an androgen receptor, but no estrogen receptor. It is possible that during growth and/or passage of the R-3327 tumor, the hormonally responsive adenocarcinoma cells do not survive and there is a gradual emergence of the nonresponsive fibrosarcoma. If, as we suspect, the receptors are found in the epithelial cells and not the stromal cells, there clearly should be considerable variation of receptor content in the different intermediary histologic forms of the tumor.


Murine leukemia cell hybrids: the quantity of TL antigens expressed by parental and hybrid cells fails to correlate with their sensitivity to TL antibody and complement. The quantity of thymus-leukemia (TL) antigens expressed by murine leukemia cells is significantly greater than that expressed by somatic hybrids of such cells. Based upon the results of 125I-lactoperoxidase labeling and antibody absorption procedures, and corrected for size differences between the two cell types, the quantity of TL antigens expressed by RADA-1 cells, a radiation-induced murine leukemia cell line of strain A/J mice, is approximately 5.0 times greater than that of somatic hybrids of RADA-1 and LM(TK)- cells. LM(TK)- cells are a thymidine kinase-deficient TL(-) mouse fibroblast cell line. The quantity of TL antigens expressed is related only in part to their susceptibility to lysis by TL antibodies and guinea pig complement (GPC). RADA-1 cells resist lysis. The quantity of TL antigens expressed by RADA-1 cells is analogous to that formed by nonneoplastic thymocytes obtained from F1 hybrids of two strains of TL(+) and TL(-) mice; cells from both strains are sensitive to TL antiserum and GPC. ASL-1 cells, a spontaneously occurring leukemia cell line of A/J mice, express TL antigens in significantly higher quantities than any of the cell types examined. Exposed to TL antisera, the quantity of TL antigens of ASL-1 cells, but not that of hybrid cells, gradually diminishes. ASL-1 cells convert over a 6-h period of exposure to antibody and guinea pig complement (GPC) resistance; hybrid cells remain sensitive. However, ASL-1 cells converted to TL antibody and GPC resistance continue for a time to express TL antigens in quantities similar to that of sensitive F1 thymocytes and resistant RADA-1 cells. RADA-1 X LM(TK)- hybrid cells, which are sensitive to TL antibodies and GPC, express the lowest quantities of TL antigens of any of the cell types examined. It is likely that differences in the quantities of TL antigens expressed by different cell lines reflect genetic mechanisms controlling TL antigen expression. The failure of TL antisera to affect the quantities of TL antigens expressed by hybrid cells is taken as an indication that genetic controls governing antigen expression may be distinguished from those involved in regulating responsiveness to specific antiserum.


Membrane alterations in irreversibly sickled cells: hemoglobin--membrane interaction. Irreversibly sickled cells (ISCs) are sickle erythrocytes which retain bipolar elongated shapes despite reoxygenation and owe their biophysical abnormalities to acquired membrane alterations. Freeze-etched membranes both of ISCs produced in vitro and ISCs isolated in vivo reveal microbodies fixed to the internal (PS) surface which obscure spectrin filaments. Intramembranous particles (IMPs) on the intramembrane (PF) surface aggregate over regions of subsurface microbodies. Electron microscopy of diaminobenzidine-treated of ISC ghosts show the microbodies to contain hemoglobin and/or hemoglobin derivatives. Scanning electron microscopy and freeze-etching demonstrate that membrane--hemoglobin S interaction in ISCs enhances the membrane loss by microspherulation. Membrane-bound hemoglobin is five times greater in in vivo ISCs than non-ISCs, and increases during ISC production, parallelling depletion of adenosine triphosphate. Polyacrylamide gel electrophoresis of ISC membranes shows the presence of high-molecular-weight heteropolymers in the pre--band 1 region, a decrease in band 4.1 and an increase in bands 7, 8, and globin. The role of cross-linked membrane protein polymers in the generation of ISCs is discussed and is synthesized in terms of a unified concept for the determinants of the genesis of ISCs.


Loss of spousal consortium.

Loss of spousal consortium. Analysis of medical malpractice decisions shows this particular type of spousal consortium claim is treated by the courts in a fashion similar to spousal consortium claims based on other types of negligent injury. That is, whether a spouse is permitted to maintain an action for loss of consortium is dependent, not on the medical malpractice basis of the claim, but on whether consortium recovery is permitted in that jurisdiction--by the spouse seeking damages--for any type of negligent injury. The common law right of a husband to seek compensation for loss of consortium due to negligent injury to his wife is well established in most U.S. jurisdictions. Four states, however, have abolished the husband's right to this cause of action--rather than perhaps be forced to extend it to the wife under a theory of constitutionally required equal protection. In contrast, 35 jurisdictions have shifted from their earlier common law view that a wife has no consortium rights and now permit her to bring such an action.


How laetrile laws affect MDs.

How laetrile laws affect MDs. A variety of problems exist in the 17 states that have passed laetrile laws. The precise legal relationship of these statutes to state food and drug laws and state medical practice acts is not well defined. The variability of the laws, state to state, is great and substances other than laetril are sometimes involved. The passage of substance-specific legislation confers "pseudo-approval" status on that substance in the public's mind. This results in a shifting of the drug approval process away from normal health regulatory channels into the political arena. Physicians should become familiar with the legal, medical, and social implications of such laws in their own states. More importantly, they need to articulate clearly to legislators the inherent problems and dangers in passing such legislation.


Will your medical records get you into trouble? Medical records frequently become legal documents. They can be the physician's best friend or worst enemy, depending on how the healthy care provider has maintained and cared for the record. Medical records that are properly maintained, including those that have properly made changes, can turn out to be a physician's staunchest ally. One cannot hope to rely on the support of a friend when the relationship has been tampered with. The health care provider has the duty to properly maintain the custody of the record, protecting the patient's right to confidentiality.


The effect of elaidic acid incorporation upon the lipid composition of Ehrlich Ascites tumor cells and of the host's liver. The incorporation of elaidic acid into Ehrlich ascites tumor cells (EATC) upon feeding the host an elaidic acid-rich diet has been investigated in the present study. The EATC lipids contained only one-half the concentration of elaidic acid found in the lipids of either the host livers or of livers from normal mice. On the other hand, elaidic acid incorporation into tumor cells was close to that of ascites fluid. This incorporation was mainly into phospholipids; the highest into choline phospholipids and ethanolamine phospholipids. Some changes in the EATC fatty acid composition were noted due to this incorporation. EATC phospholipids had reduced polyunsaturated fatty acids as compared with oleic acid-grown cells. The same was true with respect to ascites fluid phospholipids, but neutral lipids were not altered. Tumor development was accompanied by an increase in elaidic acid of the host's liver. Elaidic acid incorporation into tumor cells resulted in a reduction in the amount of all major lipids in the tumor. In contrast, elaidic acid had no effect on lipid composition of livers from normal mice and and-tumor bearing mice, and also had no effect upon the lipids of the ascites fluid that bathes the tumor cells. The incorporation of elaidic acid into the lipids of EATC, normal liver and host liver did not affect the relative composition of phospholipids in these tissues. The development of the tumor did result in decreases in triacylglycerols and esterified cholesterol, and increases in phospholipids and free cholesterol in the livers of host animals.


Distinctive medium chain wax esters, triglycerides, and diacyl glyceryl ethers in the head fats of the Pacific beaked whale, Berardius bairdi. Lipids were extracted from the mandibular fat body (jaw), the fatty forehead (melon), and the dorsal blubber of a Pacific beaked whale (Berardius bairdi) and separated into lipid classes by preparative thin layer chromatogrphy. The head fats were mixtures of wax esters and triglycerides with a very small amount of diacyl glyceryl ether. The blubber fat contained 97% wax ester and 3% triglyceride. Gas liquid chromatography (GLC) of the intac lipid classes indicated an unusually low C26-C30 range for most of the jaw and melon wax esters compared to the more normal C32-C40 molecules found in the blubber. Distinctive lower molecular weight C24-C40 triglycerides occurred in the head fats vs. the usual C44-C58 range in the blubber. Most diacyl glyceryl ethers were in the C35-C46 range, below the molecular weight of hexadecyldipalmitoyl glyceryl ether (C48). GLC of the derived fatty acid methyl esters showed that the lower molecular weight neutral lipids in the head fats were due to high levels of iso-10:0, n-10:0, iso-11:0, iso-12:0, N-12:0, and iso-13:0 acids. The wax ester fatty alcohols and the alkoxy chains of the glyceryl ethers were mostly the C14-C20 chain lengths commonly observed in marine organisms. The distinctive medium chain neutral lipids in the jaw and melon fats of this whale may be related to the postulated acoustical role of these tissues in echolocation.


Incidence and severity of experimental allergic encephalomyelitis and cerebral prostaglandin synthesis in essential fatty acid deficient and aspirin-treated rats. Experimental allergic encephalomyelitis (EAE) was induced in rats of the Lewis strain fed diets adequate or deficient in essential fatty acids (EFA). After induction of the disease, the diets were supplemented with aspirin (3.75 g/kg diet), and the effects of the drug on the course of EAE and on the synthesis of prostaglandin F (PGF) by brain slices from diseased animals and their Freund controls were examined. Aspirin supplementation delayed the onset of EAE in both dietary groups. EFA-deficient rats experienced an incidence and severity of the disease similar to that of aspirin-free, EFA-deficiet rats, while the EFA-adequate group showed a greater severity but not an increased incidence, compared to aspirin-free controls. Aspirin treatment led to an increased PGF production by brain slices from rats on either diet and not subjected to an immunochallenge. When the diet was deficient in EFA, challenge with antigen plus adjuvant or adjuvant alone tended to decrease PGF synthesis by brain slices, and when the diet was adequate in EFA, immunochallenge caused a marked depression on PGF synthesis. It was concluded that the PG synthetase inhibitor aspirin can alter the course of EAE in the rat, providing further evidence that PGs or related metabolites may be involved in the immune response in this disease.


Esterification of palmitic acid in swine aortic homogenates. The incorporation of [1-14C] palmitic acid into tissue lipids of the medial and intimal layers of swine aortic homogenates was investigated. The homogenates obtained were metabolically active as indicated by their ready incorporation of labeled palmitic acid into phospholipids, diglycerides and triglycerides in the presence of alpha-glycerophosphate in the incubation medium. Predominantly, labeling of phospholipids and especially of phosphatidylcholine was found when alpha-glycerophosphate or lysolecithin served as the fatty acid acceptor. Glycerol and monoolein did not serve as fatty acid acceptors. More than 98% of the radioactivity was recovered as the rephosphatidylcholine fraction at the level of 0.64 micromoles/ml of lysolecithin in the incubation medium.


The role of dietary fat and hepatic triglyceride secretion in cancer-induced hypertriglyceridemia. Growth of Ehrlich ascites carcinoma induces hyperlipemia in mice. In the present study using male Swiss-Webster mice, we examined whether the usual elevations of plasma triglyceride levels in cancerous mice would occur in the absence of dietary fat. Hypertiglyceridemia developed at a similar rate and to a comparable degree in tumerous mice eating a fat-free (58% glucose) diet and in those fed Purina chow. Maximal hyperlipidemia was observed on day 6 or day 8 in tumorous mice fed either diet. To determine whether the endogenous cancer-induced hyperlipidemia was due to hypersecretion of triglycerides by the liver, triglyceride secretion rates were studied 0, 2, 4, 6, 8, 10, and 12 days after tumor inoculation using Triton WR-1339. The secretory rates did not increase prior to or during the development of hypertriglyceridemia in tumorous mice and were not significantly different from those of control mice. On days 10 and 12, triglyceride secretion actually decreased in tumorous mice. Other possible causes for hypertriglyceridemia are discussed in light of the present findings of undetectable differences in triglyceride secretion rates accompanying growth of Ehrlich ascites carcinoma in mice.


Effects of essential fatty acid deficiency on prostaglandin synthesis and fatty acid composition in rat renal medulla. Studies are reported on the capacity of isolated rat renal papilla (inner medulla) to synthesize and release prostaglandin (PG) E from endogenous and exogenous precursor(s) during development of an essential fatty acid (EFA) deficiency in the rat. Weanling (21-day-old) male Sprague-Dawley rats were fed a fat-free diet supplemented with either 5% hydrogenated coconut oil (HCO) or 5% safflower oil (SO). At approximately 3, 6 and 7 weeks (6. 9 and 10 weeks of age), groups of animals fed each diet were killed for studies of PGE synthesis in the renal papillae. Differences in the fatty acid composition of the papillae lipids of the animals of each group were also determined. The in vitro production of PGE from endogenous precursor(s) was significantly reduced in the papillae from the 6-week-old rats fed the HCO diet compared to the control (SO) rats, and appeared to be near maximally depressed in the 10-week-old animals compared to that of animals fed an EFA deficient diet for over a year in an accessory experiment. Analyses of the fatty acids of the papillae lipids of the HCO groups showed that the levels of 18:2 and 20:4 were markedly reduced, and those of 16:1, 18:1 and 20:3 were elevated compared to the controls even in the 6-week-old animals, typical of an EFA deficiency. The papillae lipids of the animals fed the HCO diet were also depleted of their stores of 22:4 omega 6. A fatty acid believed to be derived by chain elongation of 20:3 omega 9, 22:3, was found in large concentrations in the papillae triglycerides of the EFA deficient rats. Incubations of exogenous arachidonic acid (20:4) in homogenates and tissue slices of the papillae of the HCO dietary groups showed that the PG synthetase was not impaired by an EFA deficiency. The rate of PGE synthesis in the papillae of the EFA deficient animals was generally enhanced when exogenous 20:4 was added, indicating that the concentration of available precursor(s) is a primary factor in the control of PGE synthesis in the papilla of the rat.


Availability of lysophosphatidylcholine in single bilayer vesicles for hydrolysis by lysophospholipase. Single bilayer vesicles were prepared from total rat liver microsomal lipids to which 5 mol% lysophosphatidylcholine had been added. The availability of lysophosphatidylcholine for enzymatic hydrolysis by lysophospholipase (EC 3.1.1.5) was found to be higher in vesicles prepared by the cholate dispersion technique when compared with sonicated vesicles. Sepharose 4 B chromatography showed that the vesicles prepared by the cholate technique were smaller than those prepared by sonication. This is in contrast to previous observations for egg phosphatidylcholine vesicles. Total rat liver microsomal extracts were found to contain proteolipid, which could be removed by ether precipitation. Cholate vesicles prepared from proteolipid-free extracts were still smaller than sonicated vesicle from this extract. Experiments with [14C] dextran entrapped in the vesicles indicate that there is no loss of the permeability barrier of the vesicles for high molecular weight solutes during vesicle treatment with lysophospholipase. The high availability of lysophosphatidylcholine in cholate vesicles of total rat liver microsomal lipids is discussed in terms of a highly asymmetric distribution of lysophosphatidylcholine over the inner and outer monolayer of the bilayer.


Separation of sulfated bile acids by high-performance liquid chromatography. In order to establish a new method for stimultaneous determination of sulfated bile acids without deconjugation, separation of 3-sulfates of unconjugated, glyco- and tauroconjugated bile acids by high-performance liquid chromatography has been undertaken. The preliminary experiment indicated that reversed phase chromatography on an ODS SC-02 column using ammonium carbonate aqueous solution/acetonitrile as a mobile phase would be promising. The ratio of peak width to retention time was varied depending upon the salt concentration. The content of water in mobile phase exerted an influence on the capacity ratio to a certain extent, but not on the resolution. The use of 0.5% ammonium carbonate/acetonitrile (26:8 and 20:8, v/v) was found to be suitable for complete resolution of sulfated cholate, chenodeoxycholate, deoxycholate, lithocholate and their glyco- and tauro-conjugates.


Biosynthesis of chenodeoxycholic acid: side-chain hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha-diol by subcellular fractions of guinea pig liver. Side-chain hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha diol was studied in subcellular fractions of guinea pig liver. The purity of the microsomal and the mitochrondrial fractions was determined with marker enzymes, and relatively little cross contamination between the particulate fractions was detected. Methods for the analysis of the incubation mixture by thin-layer chromatography and gas-chromatography-mass spectrometry were developed. Optimal assay conditons were established for the major hydroxylation reactions, namely the mitochondrial 26-hydroxylation and the microsomal 25-hydroxylation, It was found that the most active side-chain hydroxylation in the guinea pig was the microsomal 25-hydroxylation. The mitochondrial omega-hydroxylation was stereospecific, in that the rate of formation of (25R)-5 beta-cholestane-3 alpha, 7 alpha, 26-triol was 8 times greater than that of the 25S isomer. The microsomal "25" hydroxylation was not stereospecific under the conditions employed. It is concluded that the mitochondrial "26" hydroxylation (leading to the formation of (25R)-5 beta-cholestane-3 alpha, 7 alpha, 26-triol) plays an important role in the biosynthesis of chenodeoxycholic acid. The participation of microsomal 25-hydroxylation in the formation of chenodeoxycholic acids requires further investigation.


Bile acids in tissues: binding of lithocholic acid to protein. Human liver contains two forms of lithocholic acid. One form is readily extractable by 95% ethanol/0.1% ammonia (soluble lithocholate, SL), while the other remains firmly bound to the residue (tissue-bound lithocholate, TBL). TBL could be hydrolytically released using clostridial cholanoylamino acid hydrolase, suggesting a peptide link between lithocholate and protein. With bovine serum albumin (BSA), lithocholic acid showed spontaneous amino group-modifying activity. When small molecular weight lysine (alpha-t-BOC-1-lysyl-beta-naphthylamide) and arginine peptides (alpha-CBZ-di-arginyl-beta-naphthylamide) were used in place of BSA, lithocholate bound specifically to the lysine peptide. The unusual affinity for lysine suggested that this amino acid might be involved as a residue in TBL. Synthesis of lithocholyl lysines and comparison with products of acid hydrolysis of TBL established epsilon-lithocholyl lysine as the predominant form in which lithocholic acid is found in tissue bound form.


Bile acids LVII. Analysis of bile acids by high pressure liquid chromatography and mass spectrometry. Several high pressure liquid chromatographic methods for the separation of conjugated and free bile acids are presented. A mixture of synthetic conjugated bile acids has been separated by reverse-phase systems consisting of either a Waters Associated' "fatty-acid analysis" or a muBondapak/C18 column eluted with a mixture of 2-propanol/potassium phosphage buffer (pH 2.5 or 7.0). The major conjugated bile acids present in the gallbladder bile of obese subjects have been analyzed each in less than 30 min and quantitated with a U.V. detector set at 193 nm. Some of the 5 alpha- and 5 beta-isomers of conjugated bile salts could be resolved in straight-phase systems on Corasil II or muPorasil columns. Mass spectra of the conjugated bile acids obtained by electron impact were characteristics of the type of amino acid attached to the side chain, and the number of hydroxyl substituents on the nucleus. Most of the isomers could readily be differentiated by the relative intensities of the fragment ions.


Bile acids LVIII. Bile acids and colorectal cancer. Significant correlations have been reported by epidemiologists between the mortality from colorectal cancer in various populations and the consumption of meat or lipids by these populations. These have directed considerable attention to possible relationships between diet and the occurrence of this neoplasm. We have carried out studies of the composition of bile from rats as influenced by diets of varying lipid content. Two cannulas were surgically implanted to form an externalized bile duct through which bile was drained from the common duct and returned to the duodenum. Small aliquots were analyzed for total bile acids by enzymatic assay and for individual bile acids by high-pressure liquid chromatography, gas chromatography and gas chromatography-mass spectometry. Animals consuming diets highest in lipid content provided bile with the greatest amounts of bile acids. The primary bile acids, taurocholic, taurochenodeoxychilic, and tauro alpha- and beta-muricholic acids made up more than 99% of the 3 alph-hydroxy bile acids and were found in approximate molar ratio of 2:1:1. Either complete drainage of bile without return to the duodenum, or biliary tract obstruction had pronounced influence on the rate of secretion of bile and its composition.


Metabolic responses of females to high intensity interval training of different frequencies. The purpose of this investigation was to examine the effects of frequency and distance of high intensity, interval training on females. Thirty-two females participated in an eight-week program of interval run training. Subjects were assigned to either a 2 day/week or a 4 day/week group, as well as a high intensity, short distance (50,101,201 meters), or high intensity longer distance (604, 805, 1208 meters) group. Estimates of training intensity were 170% and 130% Vo2max for the short and longer distance groups, respectively. Maximal and submaximal measures of oxygen consumption (Vo2), heart rate (HR), and venous blood lactic acid were determined prior to and following the training program. After training, there was a significant increase (P less than 0.01) in Vo2max (13%) (deltax = 0.32 1/min or 5.2 ml/kg.min). Maximal VE increased approximately 12% after training (P less than 0.01). Max HR, max lactic acid, and submax Vo2 were not altered by the training. However, HR submax decreased significantly (P less than .05) after training by approximately 6%. Analysis of coveriance indicated that these changes were independent of training frequency, distance, and intensity. It was concluded that the changes in aerobic power and submaximal HR of females are independent of frequency, distance, and intensity of high-intensity interval training programs.


Maximal oxygen uptake in young women with training, inactivity, and retraining. Six young, healthy, sedentary females performed intense endurance training at a constant training stimulus (HR = 170 beats x min-1) twice a week in two 7-week periods separated by seven weeks of inactivity. Inactivity was defined as a period without scheduled exercise but with necessary daily activities. An increase in Vo2max (10-14%) and in training intensity at target heart rate (24%) were observed in both periods (p less than 0.001). Considering the intensity and duration of the program these gains are similar to those reported previously in women and men. The training response was the same in the two periods. Thus, there was no indication of beneficial effects during retraining from the previously performed activity. After the inactivity period Vo2max, as well as the work intensity at target heart rate, did not differ significantly from the pretraining observations. Thus seven weeks with no training was sufficient to neutralize the effect of a conditioning program of similar duration.


Physiological responses of international female lacrosse players to pre-season conditioning. This study examined the changes in body composition, maximum aerobic power (Vo2max) and maximum anaerobic power in seven Australian international women lacrosse players during a 3-month pre-season conditioning program. Monthly tests were conducted and the data were analyzed by an ANOVA repeated measures design and subjected to a polynomial orthogonal test of trend in the event of a significant F-ratio at the .05 level. The trend analysis for relative body fat (X = 24.9 [initial], 22.8, [first month], 23.1 [second month] and 23.1% [third month]) indicated significant linear and quadratic components since the major adjustment had occurred by the end of the first month. The players also experienced an overall average weight loss of 1.55 kg. The mean Vo2max values were: 44.0, 48.6, 52.3 and 52.9 ml/kg x min. Thus aerobic power had plateaued by the end of the second month and the trend analysis accordingly indicated significant linear and quadratic components. Anaerobic alactacid power was measured by Margaria's stair run. Both the times and power (kgm/kg x sec) exhibited significant linear trends. Post-exercise blood samples taken at the start and end of the 3-month training program indicated a significant increase (P less than .05) in lactate (X = 9.0 and 11.8 mmol/l) following a short duration maximum treadmill run.


Anthropometric estimation of body density, fat, and lean body weight in women gymnasts. Measurements from 44 highly skilled women gymnasts were used to evaluate previously derived equations for estimating body composition and to develop new equations by step-wise linear regression. True composition values were computed from body density (DB). Measures were taken of skeletal diameters (D), circumferences (C) and skin-folds (SF). Equations evaluated were those by Sloan et al. (23), F. Katch and Michael (15), Wilmore and Behnke (28), F. Katch and McArdle (18) and Weltman and V. Katch (26). With exception of the Weltman-Katch equation, correlations between true and estimated LBW's were high (.91 to .95) but underestimated true LBW 1.13 to 3.88 kg. Regression analysis suggested adjustment of ordinate values would give these equations acceptable accuracy for use with women gymnasts. New equations were derived from variables that had been selected by using factor analysis to minimize shared variance. Equations derived were DB - 1.024620 + .002024 Neck C--.001435 Supra-iliac SF--.001039 Juxta-um-bilicus SF (R.806, +/- .0061); Fat = .3798--.5809 Neck C + .3253 Abdominal C + .3007 Supra-iliac SF + .2047 Juxta-umbilicus SF, (R .891, +/- 1.29) and LBW = .3973 Height + .8357 Neck C + .4317 Shoulder C--87.203 (R .923, +/- 1.75).