The effect of adrenergic enhancement on overdrive excitation.

The effect of adrenergic enhancement (stimulation of a stellate ganglion or administration of norepinephrine) on arrhythmias induced by ventricular overdrive ("overdirve excitation") was studied in dogs with complete atrioventricular block. The following results were obtained. (1) Adrenergic enhancement may lead to abnormal ventricular rhythms. (2) A brief drive during adrenergic enhancement induced or enhanced fast ventricular rhythms. (3) The induced rhythms were characterized by an abrupt onset, a fast rate of discharge, and a moderate degree of slowing before an abrupt cessation. (4) The induced rhythms were accelerated by further drive. (5) Increasing the duration of overdrive during adrenergic enhancement resulted in overdrive suppression and not in overdrive excitation. (6) Prolonged drive could induce a few beats (instead of suppression) but at a rate below control ("inhibited excitation"). (7) The arrhythmogenic effects of overdrive and adrenergic enhancement were potentiated by the simultaneous administration of calcium. It is concluded that interventions which increase the inward calcium current (overdrive, adrenergic enhancement and higher [Ca]o) favor the onset and the maintenance of overdrive excitation.


The relation of activation boundary size to body surface QRS potential sum.

The relations of QRS amplitude sums to activation boundary size at two instants was evaluated in five normal subjects. In each subject, QRS amplitude sums from 192 simultaneously recorded torso electrocardiograms and from 35 leads from the precordial area only were obtained 10 and 15 msec after the QRS onset. Activation boundary size at these instants was taken from published studies of ventricular excitation sequence in the human heart. The relative size of electrocargiographically effective boundaries at 10 and 15 msec and the measured QRS amplitude sum at 10 msec were used to predict expected QRS amplitude sums at 15 msec. Differences between the predicted and measured QRS amplitude sums at 15 msec constitute an estimate of error in determining cardiac source size from its expressions in the body surface electrocardiogram (ECG). Results demonstrated a more consistent relation of activation boundary size to QRS sums from the 192 than from the 35 electrode array. Indirectly the results suggest summed ST segment displacement from the larger array of electrodes would be more consistently related to the extent or severity of myocardial injury than an ST segment displacement sum based on 35 precordial leads. Finally, the findings suggested that the absolute sum of an electrocardiographic measurement such as ST segment displacement would provide a better index of lesion size than ST elevation or depression only.


Right atrial versus left atrial echo zones: a proposed new criterion for determining the atrial site of retrograde preexcitation.

In a patient whose electrocardiogram (ECG) initially (1966) showed a Type A Wolff-Parkinson-White pattern, recurrent supraventricular tachycardia (SVT) developed but never subsequently showed antegrade bypass conduction. Intracardiac pacing studies (1975) revealed that premature high right atrial (induced 250-450 msec after atrial depolarization) or coronary sinus depolarization (250-550 msec) resulted in SVT. Late coronary sinus depolarization resulted in SVT without A-H prolongation. During SVT, P wave morphology changed and the coronary sinus atrial electrogram preceded that from the low right atrium; retrograde ventriculoatrial conduction time was 240 msec. Neither pacing the high right atrium or coronary sinus up to rates of 200 beats/min nor progressive atrial premature depolarizations from the high right atrium or coronary sinus resulted in antegrade bypass conduction. Failure of antegrade bypass conduction does not preclude SVT due to retrograde preexcitation and must be distinguished from atrioventricular (A-V) nodal reentry. Atrial effective refractory period (200 msec) was shorter than the minimal time required for an atrial impulse to return to the atrium (380 msec), suggesting concealed antegrade bypass conduction. Stimulation of the atrium linked to the A-V bypass results in earlier bypass activation and recovery and explains the differing high right atrial vs coronary sinus echo zones.


An unusual mechanism of arrhythmia production.

An unusual electrocardiogram (ECG) is presented which demonstrates two mechanisms of communication between the atria and the ventricles. The first appears to reflect ordinary atrio-ventricular impulse propagation. The second appears likely to represent stimulation of the ventricles by mechanical atrial systole.


Diagnosis of high anterolateral and true posterior myocardial infarction by chest wall ECG-mapping.

Precordial and posterior chest wall ST-mapping has been utilized in a patient with high anterolateral and true posterior myocardial infarction. In this patient evolution of the anterolateral component of the infarct was accurately delineated by changes in the precordial map which were not detected in the standard precordial leads. The true posterior component of the infarct was clearly diagnosed by detection of pathological Q waves and ST elevations in posterior chest wall maps, whereas right precordial standard leads had shown only suggestive reciprocal changes. The study illustrates the superiority of localized chest wall mapping over conventional 12-lead electrocardiography in detecting transmural infarction in high anterolateral and posterior regions of the left ventricle.


Idioventricular parasystolic rhythms.

A description is given of the electrocardiograms of three subjects with artificial demand pacemakers in whom no inhibition of the idioventricular rhythms occurs, thus causing unusual relationships between the artificial and the spontaneous rhythms. The latter are protected and therefore appear to be parasystolic. In the first two cases, interpolated artificial beats are inscribed in the spontaneous rhythm. In the third case, the spontaneous parasystole is intermittent and alternates with concealed extrasystolic beats originating in the same focus.


Primary ST and T wave abnormalities in the diagnosis of acute anterior myocardial infarction during permanent ventricular pacing.

The electrocardiographic diagnosis of myocardial infarction in patients with ventricular pacemakers is often difficult. This report describes the electrocardiograms of two patients with permanent ventricular pacemakers in whom the diagnosis of acute anterior myocardial infarction could be made with confidence by observing the evolution of primary ST and T wave abnormalities in the absence of specific QRS changes.


Early evaluation of a rechargeable pacemaker system.

A rechargeable demand pulse generator for permanent transvenous cardiac pacing was evaluated in 66 patients. During a cumulative follow-up period of 895 patient months there was no instance of failure of either the pulse generator or of the recharging circuit. Acceptance of the recharging concept was high, there being only one patient in whom it was necessary to replace the rechargeable generator because of inability to master the recharging technique. The early findings indicate that with proper patient selection the rechargeable pulse generator promises to be an important contribution to pacemaker therapy.


Part II: magnetic field produced by a current dipole.

To understand the MCG, electrical models of the heart must be used in which the basic building-block is usually the current dipole. The dipole's magnetic field is generally made up of two parts: 1. the contribution by the dipole element itself, which is mathematically simple; 2. the contribution by the current generated in the volume conductor by the dipole, which is complicated and depends on the boundaries; for special boundaries this contribution is zero to Bz, the component of magnetic field which is normal to the boundary. This applies to the boundaries of the semi-infinite volume conductor, the infinite slab, and the sphere. This property allows great simplification in solving the magnetic forward and inverse problems. Because of its importance, it is proven with electrolytic tank experiments. Based on this property, a method is presented for estimating the presence of those dipole combinations which produce a suppressed surface potential; it consists of a visual examination of an "arrow" display of Bz.


Part III: the effect of the torso boundaries on the magnetocardiogram.

The magnetic field produced by a current dipole is made up of two parts: the field from the dipole element, and from the current generated by the dipole in the volume conductor. It was previously shown for the semi-infinite volume conductor, infinite slab, and the sphere that the volume-current contribution is zero to the component of magnetic field which is normal to the boundary. The volume conductor in the form of the human torso is here investigated by computer simulation. Three different heart-torso models are used. The contribution to the normal field component (Bn) by the volume current (via the boundaries) and by the heart dipoles are computed. For comparison, the boundary contribution to the surface potential (V) is also computed. For Bn the three models yield a ratio of boundary to dipole contribution in the same range, with 0.28 as the average. Simple subtractions can make this ratio negligible. For V the equivalent ratio is somewhat greater. The arrow map, developed previously to display Bn over special surfaces, is shown to be valid for the human torso, for visually estimating the heart dipoles.


Part IV: visual determination of generators of the magnetocardiogram.

Previously it was shown that Bn, the component of the heart's magnetic field which is normal to the chest, is in large part produced directly by the generators in the heart; the volume-current (or boundary) contribution to Bn is relatively small. It was also shown that the distribution of Bn across the chest could be displayed as an arrow map which visually reveals the underlying dipole sources, in particular those dipole combinations which produce suppresed surface potentials but undiminished Bn. Arrow maps of two normal and one abnormal heart subject are here presented. The purpose is to demonstrate that the generators of the MCG can be coarsely estimated by visual inspection of these maps. The generators of the normal hearts are visually determined by comparing their arrow maps with those computed from the Cuffin-Selvester model. The generators of the abnormal heart are visually determined by trial-and-error, with the aid of a simple computing program. These examples are the first determinations, however approximate, of multi-dipole generators of the actual MCGs. Some possible new information is indicated.


Production of antisera against highly purified human follicle-stimulating hormone, luteinizing hormone and thyroid-stimulating hormone.

Antisera were produced in rabbits against highly purified preparations of human LH (2000 or 10,000 i.u./mg), human FSH (5500 i.u./mg), and human TSH (7-5 i.u./mg). Most rabbits produced antisera of high titre and high avidity. Cross-reactions were minimal between human TSH and human chorionic gonadotrophin (HCG) and between human FSH and HCG but marked between human LH and HCG. TSH and FSH also showed a constant but relatively weak cross-reaction. LH cross-reacted with FSH to a higher degree than did HCG. The avidity of the antisera was high. It was concluded that much of the lack of specificity recorded for glycoprotein antisera are effects of impure immunogens. Some of the true cross-reactions are probably explained by shared antigenic determinants of the beta-subunits. Unadsorbed antisera could be used for assay of FSH and TSH in plasma from pregnant women.


Serum gonadotrophin levels during development in male, female and androgenized female rats and the effect of general disturbance on high luteinizing hormone levels.

Serum LH, FSH and prolactin levels were measured in blood samples which were obtained by decapitation from groups of female, neonatally androgenized female and male Wistar rats at 2-day intervals from birth to maturity. An increase in serum FSH levels was observed between 4 and 24 days of age in both the female and androgenized female groups, while a much later increase, between 28 and 44 days of age, occurred in the males. Serum prolactin contrast, serum LH levels were in general low in all three groups of animals, although very high levels (greater than 7 ng/ml) were recorded in 22 out of 168 females and 8 out of 192 males between 4 and 28 days of age, as well as in adult males; occasional high LH levels were also seen in the androgenized females. The nature of the high serum LH levels was investigated in anaesthetized and unanaesthetized immature females by serial blood sampling using a number of techniques. Unexpectedly, only three out of 58 animals had high LH levels: two of these showed an episodic form of LH release during which levels increased to peak values and then declined within a period of about 30 min. On investigation it was found that general disturbance within the 45 min before decapitation could inhibit high LH levels in females aged between 23 and 30 days.


Comparison between the binding of 19-nortestosterone, 5alpha-dihydrotestosterone and testosterone in rat prostate and bulbocavernosus/levator ani muscle.

Specific binding of (3H)19-nortestosterone in the 100000 g cytosol of the rat bulbocavernosus/levator ani muscle (BCLA) and prostate was demonstrated by agargel electrophoresis at low temperature and compared qualitatively and quantitatively with the binding of tritiated testosterone and 5alpha-dihydrotestosterone (5alpha-DHT). Both tissues showed a greater binding affinity for 5alpha-DHT than for 19-nortestosterone, with testosterone binding the least well of the three. The relative binding affinities in the BCLA and prostate were: 19-nortestosterone:testosterone=1-4, 1.-nortestosterone: 5alpha-DHT = 0.7 The differences were statistically significant (P less than 0-02). The concentrations of receptor sites for 5alpha-DHT were 171 +/- 20 (S.D.) fmol/mg prostatic cytosol protein and 24 +/- 4 (S.D.) fmol/mg BCLA cytosol protein. The in-vitro metabolism of the three steroids in both tissues was aldo investigated by thin-layer chromatography. After incubating for 2 h at 0 degrees C the prostate was shown to reduce 26% of the 5alpha-DHT to androstanediols whilst the BCLA showed a 5% conversion. Testosterone was converted by the prostate to 5alpha-DHT (10%) and the androstanediols (6%) whilst the BCLA showed little activity in this respect. Comparing these in-vitro data with in-vivo findings from the literature, in both organs there is a positive correlation of the extent of binding in vitro to the stimulation of growth in vivo, bearing in mind that testosterone is metabolized to 5alpha-DHT in the prostate whilst in the BCLA, 5alpha-reductase is essentially absent.


Mammary nucleic acids and pituitary prolactin secretion during prolonged lactation in mice.

Lactation was prolonged until 61 days by repeated renewal of litters every week after day 12 in primiparous C3H/He strain mice. On days 12, 19, 40, and 61 of lactation, litters were removed for 5 h and after 1 h of resuckling the synthesis of DNA and RNA in the mammary gland was estimated by the incorporation of (3H)thymidine and (14C)uridine into mammary DNA and RNA in vitro respectively. Mammary nucleic acid content and pituitary and plasma levels of prolactin were also assayed. Nulliparous mice were similarly treated on day 19 of pregnancy. The percentage gain in litter weight per week was highest between days 5 and 12 of lactation, declined until days 26-33 and became steady thereafter. Mammary DNA synthesis was extremely high on day 19 of pregnancy, decreased on day 12 of lactation to less than one-fifteenth of that on day 19 of pregnancy and increased linearly therafter. Changes in mammary DNA content were not so marked, but DNA content was high on days 12 and 19 of lactation. RNA synthesis was highest on day 19 of pregnancy, abruptly decreased on days 12 and 19 of lactation and increased again with the advance of lactation. Mammary RNA content, RNA:DNA and 14C:3H ratios increased from day 19 of pregnancy to days 12-19 of lactation and decreased on days 40 and 61. While the pituitary levels of prolactin were almost constant during lactation, they were significantly higher than those on day 19 of pregnancy. There were only slight differences in plasma prolactin levels at any stage.


Effects of oestradiol-18beta, hypophysectomy and age on cytoplasmic oestradiol-17beta receptor sites in rat testis interstitial tissue.

After administration of oestradiol-17beta to intact mature and immature rats, a decrease in the testicular concentration of specific oestradiol-binding sites was observed within 1 h. The binding capacity was replenished starting about 3 h after oestradiol administration and after 5 h the oestrogen receptor level had returned to control values. Exposure of intact animals to oestradiol-17beta for longer periods (up to 24 h) did not result in an increase of receptor levels in testicular cytosol. Mature animals which were hypophysectomized for periods of up to 10 days did not show a significant change in the number of specific oestradiol-binding sites in either total testicular tissue or dissected interstitial tissue. At 15 days or longer periods after hypophysectomy, an apparent increase in receptor concentrations in total testicular cytosol was observed due to a relative increase in the amount of interstitial tissue. A specific oestradiol-binding protein is present in plasma of immature male rats aged less than 30 days. This plasma protein could also be demonstrated in the cytosol of testes of immature rats. In contrast to the cytosol receptor, which shows a moderate affinity for diethylstilbestrol (DES), the plasma protein did not bind DES. The sedimentation values of the plasma protein and the oestradiol receptor were 4 S and 8 S respectively. These differences in characteristics made it possible to demonstrate the presence of the oestradiol receptor in addition to the binding protein in testicular cytosol of rats from 14 days of age onwards. The nuclear receptor for oestradiol-17beta could be demonstrated after incubation of testicular tissue of rats from 4 days of age onwards.


Lordosis behaviour in male, female and androgenized female rats.

Sex differences in the lordodis response of adult rats to ovarian hormones were studied in a series of experiments. Male rats were less sensitive to oestradiol benzoate (OB, a single injection of 10, 100 or 1000 mug/kg or seven daily injections of 2, 10, or 50mglkg)then were female rats.  Oestradiol benzoate-primed (10 mglkg)female, but not male, rats showed dose-dependent responses to progesterone (0-4, 2-0 or 10-0 mg/kg/. male rats responded clearly to progesterone (2 mg/rat) only when primed with a high dose of OB (100 mug/rat). Display of the whole pattern of female sexual behaviour was induced in male rats by treatment with 100 mug OB and 2 mg progesterone. Female rats treated with 1 mg testosterone propionate (TP) on day 4 of life, ovariectomized as adults and tested under the same endocrine conditions as the rats described above, retained behavioural OB sensitivity but responded poorly to progesterone. Evidence is presented that ovarian secretions during development significantly modify the response of neonatally TP-treated and normal female rats to OB in adulthood.


Effect of the anti-oestrogen tamoxifen on plasma levels of luteinizing hormone, follicle-stimulating hormone, prolactin, oestradiol and progesterone in normal pre-menopausal women.

Plasma levels of LH, FSH, prolactin, oestradiol and progesterone were determined daily during two consecutive menstrual cycles in six women volunteers. During the first (control) cycle no treatment was given and normal secretion of these hormones was observed. Oral administration of tamoxifen (20 mg/day), for either 5 or 10 days of the follicular phase of the second cycle, caused no change in either the overall length of the cycle or the time of occurrence of the mid-cycle gonadotrophin surge. There was little difference in the secretion of LH, FSH and progesterone during the control and test cycles. A two- to eight-fold increase in oestradiol levels was observed during test cycle which was most pronounced at the times of mid-cycle and mid-luteal hormone peaks. There was a significant decrease in plasma prolactin levels at mid-cycle but no real difference could be seen during the remainder of the cycle. The data suggest that tamoxifen may act directly on the ovary to stimulate oestradiol release without intermediary gonadotrophin stimulation. As the drug apparently inhibited prolactin secretion even in the presence of high oestradiol levels, an alternative explanation may be that the reduced prolactin concentration permits augmented ovarian stimulation by normal concentrations of gonadotrophins.


Selection for high and low adrenal weight in mice.

Four strains of mice were used to found a heterogenous stock from which one line was selected for high adrenal weight/100 g body weight. By the eighth generation of selection, two stocks of mice were produced, one with adrenals whose absolute weight was greater than any of the parental strains. The realized heritability estimates were 75% for females and 67% for males during the period of selection, showing that a large component of variation in adrenal weight was genetic in origin. Asymmetry in response to selection was also noticed and attributed to possible variation in adrenal structure between sexes. Estimates of variances in each generation, particularly the eighth, did not show any decline which suggested that further responses to selection would be possible with further selection.


Serum follicle-stimulating hormone, luteinizing hormone and progesterone concentrations in pseudopregnant rats treated with medroxyprogesterone acetate.

Pseudopregnant rats were treated early in pseudopregnancy with 1 or 10 mg medroxyprogesterone acetate (MPA). Serum FSH, LH and progesterone concentrations were determined on days 2-20 of pseudopregnancy in treated and control rats. The mean duration of pseudopregnancy was 13-5 days in the control animals, but when animals were treated with 1 mg MPA a dioestrous period of 21-4 days was observed. A period with leucocytic vaginal smears of at least 2 months was observed after treatment with 10 mg MPA. Injection with MPA on day 3 of pseudopregnancy did not affect the serum FSH concentrations during the subsequent days. The progesterone pattern was alike in the three groups of animals, i.e. the duration of the activity of the corpora lutea was similar in all groups. However, 10 mg MPA slightly lowered progesterone concentrations on days 4-8 of pseudopregnancy. In the saline-treated rats, LH concentrations decreased from days 2-5, and remained low until they increased after day 11 of pseudopregnancy. This increase was delayed until day 20 in the animals treated with 1 mg MPA, and was not observed in the animals treated with 10 mg MPA. It is argued that the increase of LH concentration at the end of pseudopregnency is not instrumental in the decrease of peripheral progesterone concentration but rather that the decrease in the progesterone concentration leads to the increase in the LH concentration.


Binding of human growth hormone to hepatic lactogenic binding sites: regulation by oestrogens and androgens.

The binding of 125I-labelled human growth hormone (HGH) to the 'lactogenic' binding sites of rat liver membranes has been shown to be highly dependent on the oestrogen and androgen status of the membranes has been shown to be highly dependent on the oestrogen and androgen status of the animal from which the membranes were prepared. Oestradiol treatment of either male or female rats induced a highly significant rise in HGH binding. The minimum effective dose used was 2-5 mug/day and the rise in HGH binding was apparent after 4 days of treatment. Folowing cessation of oestradiol treatment of male rats HGH binding declined with a half-time of approximately 9 days. In contrast to the stimulatory effect of oestrogen, treatment of female rats with testosterone propionate (minimum effective dose 100-200 mug/day) led to a marked reduction in HGH binding. The influence of both oestrogens and androgens was confirmed following the removal of endogenous sex steroids by adrenalectomy-ovariectomy of female rats and castration of male rats. Scratchard analysis showed that, with the possible exception of adrenalectomy-ovariectomy, all pharmacologically and physiologically induced changes in HGH specific binding reflected changes in binding site capacity; there were no changes in binding affinity. While earlier studies have indicated that the oestrogen effect is primarily indirect and is mediated by the pituitary gland, the mode of action of the androgens is currently unknown. The relatively slow response of HGH binding to hormonal changes would support an indirect action for both the sex steroids. The stimulatory effect of oestrogens and the inhibitory effect of androgens may provide an explanation for the marked sex difference in HGH binding to rat liver membranes.


Pre-ovulatory changes in steroidogenesis in ovaries from immature rats treated with pregnant mare serum gonadotrophin.

The metabolism of progesterone in the 1000 g supernatant fraction of homogenates of ovaries from PMSG-treated immature rats was determined. As early as 52 h after a single injection of 50 i.u. PMSG, still before the LH surge, 5alpha-pregnane-3alpha, 20alpha-diol was identified as the main metabolite, together with small quantities of 3alpha-hydroxy-kalpha-pregnan-20-one and 5alpha-androstane-3alpha, 17beta-diol. Similar incubations of untreated rat ovaries at the same age did not produce 5alpha-pregnane-3alpha, 20alpha-diol. The quantities of 3alpha-hydroxy-5alpha-pregnan-20-one and 5alpha-androstane-3alpha, 1mbeta-diol were reduced in PMSG-treated rat ovaries as compared with control ovaries. When progesterone metabolism was examined 64 h after PMSG administration, 5-7 h after the peak of LH surge but still before ovulation, 75% of the substrate was converted to 5alpha-pregnane-3alpha, 20alpha-diol, while 3alpha-hydroxy-5alpha-pregnan-20-one as well as 5alpha-androstane-3alpha, 17beta-diol could not be detected.


Biological effects of 131I and 125I isotopes of iodine in the rat.

From the differences in radiation profiles between 131I and 125I isotopes of iodine it would be expected that they would show different effects on thyroid function. The differences should lead to lower rates of thyroid gland destruction with 125I and hence less post-irradiation hypothyroidism. This difference in biological effect has been demonstrated in rats by indirect assessment of thyroid function. In this report the long-term effects of a range of similar doses of 131I and 125I were compared, in male and female rats, by direct assessment of thyroid function. Seventeen months after receiving 25 and 125 muCi of 131I, male and female rats showed significant elevation of serum TSH concentration and a reduction in 3 h radioiodine uptake. Rats receiving 1 and 5 muCi of 131I and all doses of 125I showed no significant changes in thyroid function. These findings confirm the previously reported differences in effect between the 131I and 125I isotopes of iodine in the rat.


Stimulation of growth in the little mouse.

The new mouse mutation little (lit) in the homozygous state causes a pituitary deficiency involving at least growth hormone (GH) and prolactin. The resultant growth failure of lit/lit mice was shown to be reversed by experimental conditions that enhanced levels of GH or GH and prolactin in the circulation. Two measures of growth, actual weight gain and bone dimension, were significantly improved by the physiological processes of pregnancy and pseudopregnancy, by extra-sellar graft of a normal mouse pituitary, and by treatment with GH but not prolactin. These data confirmed pituitary dysfunction as the basic defect caused by the mutation lit and showed that the GH deficiency is responsible for growth failure. However, the biological site of gene action, the pituitary or hypothalamus, has not been established. Little mice exhibit a number of characteristics similar to those of human genetic ateleotic dwarfism Type 1, namely genetic inheritance, time of onset of growth retardation, proportionate skeletal size reduction, and pituitary GH deficiency.


Influence of the vagus and carotid sinus nerves on plasma renin in the cat.

Influence of the vagus and carotid sinus nerves on peripheral plasma renin was studied in the cat. Bilateral cervical vagotomy was followed by a sustained increase in plasma renin concentration (PRC) of anaesthetized cats made hypervolaemic by intravenous saline infusions. The increase in PRC is attributable to right vagotomy. Bilateral carotid artery occlusion in anaesthetized hypervolaemic cats, either with or without prior vagotomy, or with mechanical prevention of a rise in systemic blood pressure, resulted in no statistically significant increases in peripheral venous PRC, compared with the control animals.


Concentration of oestrogens and androgens in human ovarian venous plasma and follicular fluid throughout the menstrual cycle.

The concentrations of androstenedione, testosterone, oestrone and oestradiol-17beta were measured in peripheral and ovarian venous blood and follicular fluid of women at various stages of the menstrual cycle. The concentration of oestradiol was similar in small follicles (diameter less than 8 mm) at all stages of the menstrual cycle and in large follicles (diameter greater than or equal to 8 mm) except during the mid- and late follicular phase when the concentration reached a peak (approximately 1500 ng/ml). The concentration of androstenedione was lowest in large preovulatory follicles at midcycle at a time when the secretion into the ovarian vein was markedly increased. The concentration of testosterone in large follicles (greater than or equal to 8 mm) was unchanged during the follicular phase whereas in small follicles there was a peak at mid-cycle. The rise in the concentration of testosterone and androstenedione at mid-cycle in peripheral plasma may be due to increased secretion by the preovulatory follicle into the ovarian vein. It is suggested that the relatively low concentration of androstenedione in follicular fluid of the preovulatory follicle arises from increased aromatization by granulosa cells in the course of oestrogen synthesis.


Induction of luteinizing hormone release by gonadal steroids in the ovariectomized domestic hen.

The ability of intramuscular injections of gonadal steroids to exert a positive feedback action on LH secretion was investigated in the ovariectomized hen. Plasma LH was measured by radioimmunoassay. Single injections of progesterone (dose range: 0.05-10 mg/kg) or oestradiol benzoate (dose range: 0.01-1 mg/kg) did not result in an increase in plasma LH concentration. After priming with 0.1 mg oestradiol benzoate/kg on alternate days for 7 days and with 0.5 mg progesterone/kg on days 5, 6 and 7, a single injection of progesterone on day 8 (dose range: 0.1-2 mg/kg) caused the plasma LH concentration to start increasing after 15 to 30 min. Peak LH concentration was reached around 1.5-2 h after injection. The magnitude of LH response to progesterone was dose related. In contrast, a single injection of oestradiol benzoate (dose range: 0.01-1 mg/kg) failed to stimulate LH release in the oestrogen-progesterone primed ovariectomized (O-P-OVX) hen. A single injection of testosterone (dose range: 0.1-2.0 mg/kg) failed to stimulate LH release in ten out of 12 O-P-OVX hens. A small increase in LH secretion was observed in the two remaining birds. When oestrogen or progesterone was omitted from the priming schedule, a LH positive feedback response to a single injection of progesterone was not observed. Increasing or decreasing the mount of oestrogen or progesterone in the priming schedule modified the LH response to a single injection of progesterone on the day following the last priming injection. This suggested that a critical oestrogen to progesterone ratio was required to prime the LH positive feedback mechanism. It is suggested that, in the hen, the release of LH is facilitated by the positive feedback effect of a combination of oestrogen and progesterone in a two-phase process. The first is the priming phase, which depends on the presence in the blood of oestrogen and progesterone; the second is the ind  .uctive phase, which depends only on an incremental change in plasma progesterone concentration. Oestrogen is not involved in the induceive phase.


Cleft palate induction in hamster fetuses by glucocorticoid hormones and their synthetic analogues.

The effect of prenatal administration of different doses of cortisone, corticosterone, dexamethasone, triamcinolone and prednisolone on the fetus and its palatal development was studied. All the glucocorticoids, except cortisone, produced cleft palate in the fetuses. Both the total frequency and morphologically different types of cleft palate were related to the dose of the teratogen. Triamcinolone appeared to be more potent than other glucocorticoid in inducing cleft palate. An association was noted between fetal growth inhibition, the dose of the teratogen and the frequency and type of cleft palate.


Distortion of patches of retinal degeneration in chimaeric mice.

Estimation of the proportion of degenrate retina in rd/rd and +/+ (or +/rd) chimaeras, using a linear analysis of histological sections, suggests a considerable preponderance of the normal phenotype, while analyses based on the area of the surviving tissue suggest that the proportion of each component is similar to that in other tissues. This argues against the validity of the linear analyses used by other authors. It is suggested that cell movement occurs in the outer nuclear layer, following the degeneration of the rd/rd population, and results in a distortion of the original patches of normal cells.


Patches in the livers of chimaeric mice.

Sections of adult chimaeric livers have been histochemically stained for beta-glucuronidase activity and patches of two cell populations visualized. A one-dimensional clonal analysis has been used to estimate the number of coherent clones in the adult liver. The data are consistent with a total of 9-22 million regular, coherent clones, comprising 10-34 nuclei, or a smaller number of irregular, branched coherent clones. Both of these alternatives suggest considerable cell mixing during liver morphogenesis.


[Stability of determination and differentiation of the somatic sexual characters in Nereis pelagica L. (Annelida polychaeta)].

Experiments of regeneration in situ or on grafts were carried out to test the stability of determination of the somatic sexual characters in Nereis pelagica. The sexual characters of the parapodial cirri (male and female swellings, male crenellations) are always expressed on stump or regenerate according to the genetic sex. Supernumary parapodia which developed at the site of junction of the heterologous faces of host and graft of opposite sexes, might have the characters of either sex; this result can be interpreted by supposing that a supernumary parapodium is derived from tissues of either host or graft, of the corresponding sex. Conversely, the pygidial papillae, which normally occur only on the heteronereid male, will appear on regenerating female pygidia, triggered to transform to the heteronereid condition naturally or by decerebration, with a frequency depending on the age of the regenerate, the length of the regenerate, and the genital condition of both the stump and the regenerate. It is concluded that the presence of the papillae is not a sex-specific character, but that their development is normally inhibited in the maturing female.


Target discrimination in regenerating insect sensory nerve.

The paired abdominal cerci of the cricket Acheta domesticus are mechanosensory appendages which regenerate readily when amputated during larval life. Their peripherally-located sense cells form axons which project centrally as a purely sensory nerve to the terminal abdominal ganglion. In an attempt to analyze some of the factors which guide a regenerating sensory nerve to correct central terminations, implants of homologous, supernumerary terminal ganglia were made in cricket larvae and the host cerci amputated. The possibility that implants with multiple nerve stumps might release an attracting substance was considered. Surgical procedures used were (1) implant in posterior abdomen; (2) implant in posterior abdomen, ipsilateral to chronic cercal deprivation; (3) implant in mesothoracic leg socket, adjacent to heterotopically-transplanted regenerated cercus; (4) implant in posterior abdomen, ipsilateral host cercal motor nerve sectioned; (5) implant in posterior abdomen, ipsilateral margin of host terminal ganglion wounded. Results were determined after the adult molt, by conventional histology or by cobalt chloride filling of regenerated cercal nerves. In all procedures except (3) and (4), the regenerated afferent nerve bypassed the implant and terminated in the host terminal ganglion. In (3), the regenerated fibers from cercal grafts bypassed the implant; terminations were not found. In (4), some regenerated cercal axons connected with the implant and the majority terminated in the host ganglion. It is suggested that regenerating cercal afferents may depend in a facultative way on the cercal motor nerve as a pathway guide but there is as yet no clear evidence for a trophic influence from the central nervous system.


Observations on the migration and proliferation of gonocytes in Xenopus laevis.

The process of primordial germ cell formation in the normal course of development of Xenopus laevis was examined with a light microscope on paraffin and Epon sections of embryos or tadpoles, extending over the period from the gastrula to the feeding tadpole stage. Positional changes of gonocytes with development were nearly the same as those reported on the same species by Blackler (1958) and Whitington & Dixon (1975). The following points were newly demonstrated. Gonocytes which have been located in a deep endodermal position till mid tail-bud stage come to be located in a rather peripheral region of the endoderm cell mass at stage 31 (late tail-bud), suggesting that the initial step of migration of the gonocytes towards the future genital ridge has already begun at this stage. Gonocytes at stages 33/34 and 35/36 were observed in a more dorsal part of the endoderm than at stage 31. Gonocytes which seem to have begun their migration are roundish in external shape and have a large intercellular space around them. At stage 40 gonocytes were located in the dorsal endodermal crest, and at stage 41 gonocytes were found with cell bodies extending over both the dorsal endoderm crest and the dorsal mesentery, indicating that the separation of the gonocytes from the endoderm was in progress at this stage. The present results seem to indicate that gonocytes migrate not passively but actively from the deep endodermal position to the genital ridge, passing through the dorsal mesentery. Counting the number of gonocytes at successive stages of development revealed that gonocytes proliferated exponentially throughout the developmental stages from gastrula to tadpole.


Incorporation of tritiated cytochalasin B into ectodermal explants of the amphibian gastrula.

Ectodermal explants from gastrulae of Triturus alpestris were exposed to tritiated cytochalasin B (5 and 10 mug/ml) for 1/2-2 1/2 h. The flat explants failed to heal into compact spheres and the component cells gradually rounded up. Radioactivity in the fixed and sectioned material was analysed by light and electron microscopic autoradiography. Silver grains were found predominantly over the yolk platelets, but were also scattered over other cellular components. Areas containing pigment granules or the feltwork material, present in the apices of dissociating cells of the superficial layer, exhibited higher activity than areas containing mitochondria or cytoplasmic matrix. Lipid droplets and nuclei showed comparatively little activity. The results are discussed in relation to previous findings on the uptake of tritiated cytochalasin D by cell fractions.


[Comparative study of the cells of the freshwater planarian Polycelis tenuis (Iijima) using dissociated fragments cultivated in vitro: ultrastructural aspects and incorporation of (3H) leucine and (3H) uridine].

Study of planaria cells, which are the result of dissociated fragments cultivated in vitro, allows the evolution of two cell groups to be followed: (1) Differentiated cells, which do not divide, and do not dedifferentiate either, incorporate leucine and uridine at a rate which remains stable for the whole duration of the culture. (2) Undifferentiated cells have a mitotic and incorporation rate of leucine and uridine which varies during the period of culture. After 10 days of culture they demonstrate the characteristics of cells undergoing differentiation. These results are in agreement with those of other authors who attribute an essential role to undifferentiated cells during regeneration of the adult planaria.


Cytological and microspectrophotometric analysis of mesodermalized explants of Triturus gastrula ectoderm.

Using isolated presumptive ectoderm of the newt (Triturus pyrrhogaster) embryos as a reactor and extract of rat bone marrow as a mesodermal inductor, changes of cell number and mitotic index of the reactor cells were studied. In early stages of cultivation the increase in cell number in the mesodermalized ectodermal piece was slower than in the non-mesodermalized epidermal piece; but after 24 h it showed abrupt increase and reached a cell population equal to that of the control at 48 h of cultivation. In the experimental series, the mitotic index was 0 at 4 h after the application of the inducing stimulus, but increased precipitously in the next 8 h and reached a level of 4-4% at 12 h and thereafter decreased gradually. The cell cycle stopped at the S phase and stayed in it for several hours after the application of inductor. A sudden fall in cell number, observed in the mesodermalized epidermal piece between the 4th and the 8th h after the application of inducing stimulus, seems to be attributable to cell death which was brought about by the inducing stimulus. In the histogenetic process phases of repression on mitosis by an inducing stimulus, cell proliferation and nonproliferation seem to succeed each other.


Effect of ascorbic acid deficiency on mouse second molar tooth germs cultivated in vitro.

Mandibular second molar tooth germs from two-day old mice were cultured in vitro, on millipore membranes, for periods of up to 20 days in liquid medium with or without added ascorbic acid. Tooth germs grown in ascorbate medium were characterized by relatively normal growth, differentiation, morphology and histology. Cuspation patterns were maintained. The epithelial root sheath continued to grow along the millipore membrane. Tooth germs cultured in ascorbate-deficient medium manifested a consistent and striking failure in maintenance of differentiated odontoblastic and ameloblastic tissue with arrest of predentin synthesis, severe structural collapse and reduction in size. Cuspation patterns were lost in scorbutic molars, with sinking of surface layers into pulpal tissue and flattening of the entire organ. This resulted in a lack of recognizable morphology and in severe disorganization of tissues. Only growing areas of the root sheath with associated proliferation of preameloblasts and pre-odontoblasts and adjacent pulpal tissue remained normal and refractory to ascorbate deficiency. Odontoblastic as well as ameloblastic layers were disrupted and cells were dedifferentiated. Newly differentiated odontoblasts became highly vacuolated when they became polarized and started to secrete extracellular matrix.


Membrane transport by murine lymphocytes. I. A rapid sampling technique as applied to the adenosine and thymidine systems.

We have developed a rapid sampling technique for animal cells in suspension for the purpose of measuring membrane transport in lymphocytes. The method involves rapid centrifugation of cells through a layer of silicone oil into perchloric acid after incubation periods as short as 4 s. Using this method we have described the uptake of thymidine and the uptake and transport systems of adenosine by murine bulk nonadherent spleen cells. The two uptake systems are markedly different. Adenosine was shown to be taken up by classical carrier-mediated diffusion, while thymidine was not. In addition we have explored the metabolism of the two nucleosides under the conditions we employed for measuring transport or uptake; Both nucleosides are phosphorylated extensively. We also investigated the uptake and metabolism of thymidine over a 2-h interval the standard time used to measure DNA synthesis in lymphocytes. Unless cells were separated from medium by centrifugation through oil before TCA addition, the TCA precipitable counts exceeded the total radioactive uptake. Hence the standard method for measuring thymidine utilization yields estimates under these conditions which can be as much as 100% too high.


Induction of IgG in young nude mice by lipid A or thymus grafts.

Postnatal serum concentrations of IgG2a of paternal allotype, measured in congenitally thymusless nude mice, increase with kinetics and titers comparable to their normal congeneic counterparts. Lipid A, the mitogenic part of LPS, stimulates IgG synthesis in nude mice when it is given 7 days after birth. IgG concentrations at 15 days of age are 6- to 8-fold higher than in untreated control nudes; this is considerably lower, however, than in normal mice, which show up to 45-fold higher IgG2ab levels after lipid A treatment. A thymus graft from nearly congeneic donors of the same age, transplanted at 4 days after birth, also stimulates long-lasting IgG synthesis in the nude recipients. If the grafted nudes are injected with lipid A 3 days later, IgG synthesis is further stimulated 8- to 16-fold. The data are discussed in relation to the thymus dependency of IgG production and the conditions for lipid A stimulation.


Alternative pathway of complement: recruitment of precursor properdin by the labile C3/C5 convertase and the potentiation of the pathway.

In this study the physiological role of properdin and the differential subunit composition of the solid phase enzymes of the pathway have been explored. Cell-bound C3 and C5 convertase differ in their C3b requirement. Apparently one molecule of C3b is sufficient to allow formation of C3 convertase (C3b,B), whereas two or more are required for generation of C5 convertase (C3bn,B). This conclusion was drawn from results indicating the critical role of the spacial distribution of C3b molecules on the cell surface in enzyme formation. While the C3/C5 convertase is fully capable of acting on C5 and thereby initiating the assembly of the cytolytic membrane attack complex, it is exceedingly  labile and vulnerable to destruction by the C3b inactivator. It is the apparent role of properdin to confer a degree of stability upon the labile enzyme and to protect its C3 convertase function against enzymatic destruction. To achieve these effects, precursor properdin (pre-P) is recruited in a binding-activation reaction by the labile C3/C5 convertase. Multiple C3b molecules appear to be needed for the formation of properdin-activating principle. Three modes of regulation have been described, which involve spontaneous dissociation enzymatic degradation by C3b inactivator and disassembly by beta1H. The functional differences of pre-P and activated properdin (P) were delineated, pre-P displaying a weak affinity for C3b and P the capacity of strong interaction, P generating a soluble C3 convertase in serum and pre-P being unable to do so. Because of the profound differences between native pre-P and the laboratory product P, the question was raised as to whether soluble P represents an unphysiological form of the protein. On the basis of this and other studies, the conclusion was reached that in vitro properdin recruitment constitutes the terminal event of the properdin pathway, and that properdin augments the function of C3/C5 convertase without changing its substrate specificity.


Inherited structural polymorphism in human C2: evidence for genetic linkage between C2 and Bf.

Structural variation in the second component of human complement was identified in about 4% of serum samples from random unrelated individuals of all the major races. Three forms of C2 have been identified by isoelectric focusing in polyacrylamide gel and development of patterns in agarose gel containing antibody-sensitized sheep red cells and C2-deficient serum: C2 C (common), C2 A (acidic), and C2 B (basic). The C2 variants were shown to be inherited as autosomal codominant traits, and suggestive evidence for close linkage between C2 and Bf was obtained.


Murine model for human secondary amyloidosis: genetic variability of the acute-phase serum protein SAA response to endotoxins and casein.

The serum precursor SAA of the secondary amyloid protein AA has been detected by solid-phase radioimmunoassay as a normal serum alpha-globulin of mol wt 160,000, which dissociates to a more stable 12,500 dalton moiety on treatment with formic acid. In 12 strains of mice, including T-cell-deficient nude mice, treated with the amyloid-inducing agents lipopolysaccharide (LPS) or casein, SAA behaved as an acute-phase reactant. SAA concentration rose to about 750 mug/ml by 24 h and returned to less than 1 mug/ml by 48 h. Since the amyloid-resistant colchicine-treated mice and AJ mice had a normal SAA response to LPS, it appears that their resistance to amyloid induction is due to the nature of their SAA processing rather than decreased SAA production. C3H/HeJ mice, which have defective B-lymphocyte responses to LPS, required extremely high dosages of LPS to cause SAA elevation, although their SAA response to casein was normal. This suggests that SAA is an acute-phase protein produced as a result of B-lymphocyte stimulation. Preliminary evidence suggests that at the height of an acute SAA response, liver homogenates are particularly rich in protein AA cross-reacting material.


In vitro stimulation of lymphocytes by neutral proteinases from human polymorphonuclear leukocyte granules.

Two neutral proteinases from human polymorphonuclear leukocytes (PMN), an elastase and the chymotrypsin-like cathepsin G, were purified, and their actions on lymphocytes in culture were studied. Both PMN proteinases stimulate lymphocytes from human peripheral blood and from mouse spleen in vitro, but do not affect thymic cells from either normal or hydrocortisone-treated mice. In stimulated mouse spleen cell cultures, most of the developing blast cells bear surface immunoglobulins, and subsequently appear to engage in antibody synthesis. In their stimulatory action, the two PMN proteinases thus resemble the classic B-cell mitogen LPS and neutral pancreatic proteinases such as trypsin, chymotrypsin, and elastase. The effects of proteinase inhibitors indicate that lymphocyte stimulation is dependent on the proteolytic activity of the enzymes. This work suggests that PMN proteinases, which are released at sites of inflammation, may modulate the function of lymphocytes.


Cell surface antigens of human malignant melanoma. II. Serological typing with immune adherence assays and definition of two new surface antigens.

Immune adherence assays revealed that 10 out of 18 melanoma patients had demonstrable antibody to surface antigens of autologous cultured melanoma cells, with serum titers ranging from 1/4 to 1/160. Autologous fibroblasts showed no reactions with these sera. Antibody from individual patients showed reproducible temperature preference for maximal reactivity. Two new melanoma antigenic systems were defined in this study. The first, BD, was restricted to autologous melanoma and could not be demonstrated in absorption tests on 12 allogeneic melanoma cell lines. The other, AH, was found on 5 of 12 melanomas and represents a class of shared melanoma surface antigens. Neither BD nor AH antigen was found on normal cells from autologous, allogeneic, or xenogeneic sources or on any nonmelanoma tumor cell line. Methods are now available to develop a comprehensive serological classification of the surface antigens of melanoma.


Natural concepts in pigeons.

Pigeons learned to discriminate pictures of trees, bodies of water, or a particular person in three separate experiments. Pictures being seen for the first time were discriminated almost as well as pictures seen in training. The pigeons in each experiment showed similar patterns of errors and correct discrimination.


Aversions to unflavored water and cup drinking produced by delayed sickness.

Rats drank from a cup and were then injected with lithium chloride. The result was an apparent association between the appearance of the cup and toxicosis. In Experiment 1, avoidance of drinking unflavored water from the cup was apparent after two trials in which toxicosis was induced either immediately or 1/2 hr. after such drinking. Consumption of sucrose solution from the cup prior to toxicosis, however, did not produce a statistically reliable aversion to drinking unflavored water from the cup. In Experiment 2, rats were repeatedly subjected to toxicosis 0.0, .5, 1.5, 4.5, or 18.0 hr. after drinking unflavored water from a cup. A reduction in drinking from the cup was inversely related to the delay of toxicosis, but only the 0.0- and .5-hr.-delay groups exhibited statistically reliable aversions. A later phase excluded the possibility that sensitization alone could account for the cup aversions. Marked aversions to the unflavored water itself were obtained in Experiment 1, but in Experiment 2 any such aversions were so weak that they could not have been responsible for the cup aversions.


Effects of priming unconditioned stimulus representation in short-term memory on Pavlovian conditioning.

A series of four experiments evaluated eyelid conditioning in the rabbit under circumstances in which the unconditioned stimulus (US) could variously be assumed to be prerepresented (primed) in short-term memory at the time of its presentation in pairing with a conditioned stimulus (CS). In both between- and within-subjects comparisons, less conditioning resulted when CS-US pairings were shortly preceded by US presentations than when not. The decremental effect of the pretrial priming US depended upon the similarity of such US to the subsequent conditioning US included in the CS-US pairing and could be removed by the interpolation of a distractor stimulus between the priming US and the CS-US pair. Finally, a similar decrement in conditioning was observed if a weak priming US was administered prior to the conditioning US but after the CS, that is, within the CS-US interval. The overall pattern of data supports Wagner's thesis that stimuli are rendered generally less effective when they are primed in short-term memory.


Limulus psychophysics: spectral sensitivity of the ventral eye.

The ventral eye of Limulus contains only one type of photoreceptor. Behaviors mediated by the ventral eye provide an unambiguous representation of the function of that single-receptor type. Such behaviors can be compared with the results of acute, single-cell investigations to assay for the contributions of candidate neural codes in the regulation of behavior (cf. Uttal, 1973). Using an unconditioned tail movement as the response, the psychophysical spectral sensitivity function mediated by the ventral eye of Limulus was measured. This psychophysical function peaked at 525 nm and showed evidence of strong absorption by the cuticle in the short-wavelength portion of the spectrum. Under the conditions of the present experiment, the threshold was 4.5 quanta absorbed per receptor per msec at 525 nm. The spectral transmission of the ventral eye cuticle was also measured. After correction for cuticle absorption, the psychophysical spectral sensitivity function was compared with previously reported spectral sensitivity functions obtained either from electrophysiologic (Millecchia, Bradbury, and Mauro, 1966; Nolte and Brown, 1970) or from microspectrophotometric (Murry, 1966) recordings from single, isolated ventral eye photoreceptor cells. All three functions exhibit a sensitivity peak near 525 nm; the corrected psychophysical and microspectrophotometric functions both display a second peak near 425 nm. A second experiment confirmed the reliability and validity of the 425-nm peak. The coding implications of these findings were explored. A preliminary finding is that, in dichromatic or trichromatic visual systems, two-peaked receptor spectral sensitivity functions produce central, opponent response systems that are qualitatively the same as those produced by single-peaked receptors.


Reform in the United States: its impact on medicine and education for family practice.

The historical concept of reform is useful as an aid to understand the modern rise of family practice education. Beginning about 1890, historians have identified several themes of reform in the United States which have been expressed culturally, politically, and socially. Each of these themes, agrarianism, bureaucratization of the professions, and utopianism, has influenced medicine and medical education--first at the turn of the century in the activities of the AMA in promoting public health and in establishing the natural sciences as a basis for medical education and practice. Since the end of World War II, additional reform themes have become visible which are also influencing medicine. Among these are humanism, consumerism, and the women's movement. It is the author's thesis that the present vitality and future development of family practice as a discipline is more dependent on its capacity and willingness to be identified with these expressions of reform than on its negotiations and compromises within the medical education establishment.


An information system for family practice. Part 1: Defining the practice population.

Information systems for family practice are vital in its development as an academic discipline, in the teaching and learning process which ultimately improves the quality of care, and in the planning processes which must be used to rationalize the distribution of scarce resources in the health-care field. The provision of sufficient data for these purposes demands a flexible system, generally one based on the computer as a data storing and analyzing tool. Such a system has been developed in the teaching practices of the Department of Family Medicine, University of Western Ontario; the methods employed and the uses for that system are to be described in a series of four papers. This first paper describes the methods developed for gathering demographic information on the practice population.


An information system for family practice. Part 2: The value of defining a practice population.

The gathering of information on the practice population is essential for practice monitoring, preventive medicine, and research. The minimum necessary information is the age and sex of individuals cared for in the practice. This allows the expression of age-sex specific morbidity rates for the at-risk population. In the Department of Family Medicine, University of Western Ontario, practice census information has been used to determine the suitable size for a teaching practice, the representativeness of our practices in terms of age, sex, residence location, and morbidity, and for the production of at-risk registers based on age and sex.


Injection therapy for varicose veins.

The varicose tendency cannot be cured but it can be controlled. Injection compression sclerotherapy, if performed competently on selected patients, is an effective treatment. It is a relatively simple, economical, safe, and ambulatory form of therapy which has a major place in the management of varicose veins. The technique for injection is subject to considerable variation, but the necessity for post injection compression of the veins is absolute. Post injection compression reduces the potential for recurrence by preventing return of the blood to the vein after injection and maintaining contact of the intimal surfaces so that bonding can occur, thus converting the vein from a tube to a solid fibrotic cord. Injection compression sclerotherapy is the best treatment of selected varicosities.


On the diversity of sperm histones in the vertebrates: II. A cytochemical study of the basic protein transitions during spermiogenesis in the cartilaginous fish Hydrolagus colliei.

Spermiogenesis in the ratfish (Hydrolagus colliei) is characterized by unusual changes in the basic proteins of the nucleus. Cytochemical analysis indicates that early spermatids in this cartilaginous fish contain the somatic type of histones. However, late spermatids contain the salmon type of sperm histone whereas spermatozoa display the mouse/grasshopper type designated by Bloch ('69). Such an unusual cytochemical shift from protamine in the spermatid to "stable protamine" in the sperm has not been documented heretofore.


Body temperature of the lizard (Anolis carolinensis): effect of parietalectomy.

Thermal behavior of parietalectomized, sham-parietalectomized or intact lizards (Anolis carolinensis) was recorded in a test chamber containing moving photothermal gradients. Following parietalectomy, animals chose significantly higher temperatures than sham-parietalectomized or intact control animals, which chose lower and statistically identical temperatures. When pre-surgical and post-surgical means are compared within groups, the eccritic temperature was 2.10 degrees C higher following parietalectomy, 0.72 degrees C higher following sham-parietalectomy, and 0.31 degrees C higher in intact controls during the post-operative measurements. The effects of parietalectomy indicate that the parietalpineal complex may be involved in behavioral thermoregulation by precisely regulating exposure to heat sources (e.g. sunlight).


Parietalectomy and thermal selection in the lizard Sceloporus magister.

Lizards were acclimatized to various regimes of temperature (15 degrees, 35 degrees C) and photoperiod (LD 08:16, 16:8). Parietalectomized, sham operated, and control animals were placed in thermal gradients and their body temperatures monitored for periods of up to 15 days. Daily rhythms of thermal selection were evident with higher temperatures selected in late photophase and lower temperatures selected in scotophase. Thermal selection was more variable in scotophase than in photophase. Parietalectomized lizards chose significantly higher body temperatures than did shams or controls. Acclimatization to temperature and photoperiod had little or no effect on the thermal preferendum. The preferred body temperature of controls was 33.2 degrees C +/- 3.59. Length of time in the gradient tended to change thermal preference, especially in lizards acclimated to 15 degrees C. Through interactions with the pineal gland the parietal eye is probably important in synchronizing many bodily functions with photoperiod.


Phospholipase activity of sea urchin sperm: its possible involvement in membrane fusion.

Phospholipase activity of egg-water treated Arbacia punctulata and Lytechinus variegatus sperm was shown to result from the sequential action of phospholipase A and lysophospholipase. A transient burst of phospholipase A activity followed induction of the acrosome reaction with egg water. The time of appearance suggested an acrosomal localization of the enzyme. The peak activity of phospholipase A correlated with initiation of sperm-egg fusion, suggesting a role for sea urchin sperm phospholipase A in membrane fusion and/or egg activation during fertilization.


28 s and 18 s ribonucleic acid from mammalian spermatozoa.

The majority of RNA is spermatozoa from the epididymis and ductus deferens of mice was found to be 28 s and 18 s RNA. This RNA was also seen in human ejaculated spermatozoa. Our evidence indicates that little or none of the 28 s and 18 s RNA is transcribed in the maturing mouse spermatozoa and that the majority is synthesized in the primary spermatocyte. This RNA may be necessary to maintain post-meiotic translation during spermatogenesis.


Muscle satellite cells in urodele amphibians: faciliatated identification of satellite cells using ruthenium red staining.

The ruthenium red (RR) stained forelimb musculature of three species of urodeles Triturus (Notophthalmus) viridescens, Amblystoma maculatum, Amblystoma opacum in various stages of growth were examined with the electron microscope for the presence of satellite cells. It was found that RR staining facilitated greatly the identification of satellite cells. In young larvae of all three species satellite cells were detected with a frequency of 29% to 48% per total number of nuclei. In adult Triturus and Amblystoma maculatum satellite cells were no longer detected; instead "pericytes" as described by Hay ('74) were seen with a frequency of 12% and 3% respectively. During metamorphosis of Triturus satellite cells, with part of their myofiber-satellite cell intercellular space filled with basement membrane material, occurred at a peak frequency. The cells presumably are intermediate in the formation of "pericytes." At ten days after metamorphosis satellite cells and intermediate cells were no longer detected and the limb musculature contained only "pericytes" similar to the ones observed in adult newts. The significance of the presence of satellite cells in relation to limb regeneration and muscle regeneration is discussed.


The role of divalent cations in activation of the sea urchin egg. I. Effect of fertilization on divalent cation content.

The Ca and Mg content of unfertilized sea urchin eggs (3 and 21 mumole/ml eggs) remains remarkably constant over periods of hours, even when the eggs are suspended in Ca- or Mg-free sea water. After fertilization the Ca content of eggs in regular sea water increases sharply by about 20%, followed by a decrease to the unfertilized level by 40 minutes. However, if the fertilized eggs are washed three minutes in Ca-free sea water a sharp decrease in the Ca content occurs amounting to 30% of the total in the first 40 minutes, with little change thereafter. Suspension of the eggs in Ca-free sea water results in an even greater loss of Ca amounting to about 43% of the total in the same time interval, followed by a continuing slow loss. It is concluded that fertilization initiates the intracellular release of Ca, which is then extruded. For unwashed eggs this change is masked by the simultaneous generation of new extra-cellular coats with high affinity for Ca. Changes in the Mg content of fertilized eggs follow the same general pattern except that absorption of this divalent cation to the extracellular coats is minimal.


Ultrastructural characterization of the accessory lobes of Lachi (Hofmann's nuclei) in the nerve cord of the chick. I. Axoglial synapses.

Light microscopic observations of the accessory lobes of Lachi of one-day-old chicks show that this tissue contains abundant amounts of glycogen and consists of cells which are similar in appearance to those of the glycogen body. Ultrastructural studies reported here for the first time confirm the presence of glycogen-rich cells in the accessory lobes and reveal that these cells are intimately associated with nerve axons. The finding of synaptic complexes and other junctional specializations between nerves and accessory lobe cells suggests that they may have a functional relationship with the nervous system. It is felt that the accessory lobe cells may be neuroglia, possibly of the astrocytic type, which have an innate capacity for glycogen storage. While the functional significance of such glycogen remains obscure, the close morphological association between neurons and the accessory lobe cells enhances the hypothesis put forth by us regarding the glycogen body, namely that neural glycogen is involved in myelin synthesis in the avian nervous system.


Hypoxia: a succinate-fumerate electron shuttle between peripheral cells and lung.

The objective of this investigation was to determine if the succinate that accumulates in anoxic or hypoxic tissues of mammals is (a) increased in concentration in the blood, (b) excreted in the urine or (c) recycled in some manner. Rats were subjected to 0.4 atm and the plasma analyzed for succinate and fumarate at 2 hours, 24 hours and 28 days. Significant increases of succinate or succinate plus fumarate were obtained at 2 hours and 28  days at 0.4 atm. Analysis of 24-hour samples of urine obtained from controls and animals at 0.4 atm for 28 days demonstrated that no substantial increase in succinate excretion occurred with acclimation. Lung slices were incubated in Krebs-Ringer bicarbonate and succinate and gassed with O2:CO2 (95:5). Such oxygenated lung slices not only utilized succinate but produced a comparable quantity of fumerate plus malate. It is concluded that succinate produced from fumarate and alpha-ketoglutarate in peripheral hypotic tissue is transported by the blood to the oxygenated lungs. There it is oxidized to fumarate and recycled as fumarate and malate to the periphery. In this way metabolites can act as electron shuttles between peripheral cells and lung.


Breakdown of the germinal vesicle in pig oocytes in vivo and in vitro.

The breakdown of the pig germinal vesicle (GV) was studied in follicular oocytes matured in vivo and in vitro. For better characterization, the whole process was divided into four well-defined stages, based on the chromatin changes, and on nucleolus and nuclear membrane disappearance. In the intact germinal vesicle (GV I) nuclear membrane and nucleolus are clearly visible and chromatin forms a ring or horseshoe around the nucleolus. In the GV II a fre orceinpositive structures (chromocenters) on the nuclear membrane can be detected. For the GV III slightly stained chromatin clumps, localized especially around the nucleolus, and the beginning of strand formation are typical. In the last stage - GV IV - the nuclear membrane is less distinct and the nucleolus disappears completely. Chromatin is seen as an irregular network or as individual bivalents. According to these criteria GV breakdown in vivo was completed in most oocytes between 20 to 24 hours after HCG injection. In culture a similar stage of development was reached between 16 to 20 hours. This difference in the progress of nuclear changes appeared at the beginning of nuclear maturation and remained unchanged throughout the whole period studied.


Morphology and kinetics of the hamster sperm acrosome reaction.

The morphology and kinetics of the normal acrosome reaction were examined in vitro using hamster sperm incubated in detoxified sera. The reaction involved either swelling and elevation or crenulation and fragmentation of the acrosomal cap. Swelling and elevation occurred during both normal and degenerative reactions, as reported by others. Crenulation with subsequent fragmentation of the cap was observed during normal reactions. Early crenulation of the acrosome could be induced by cold shock (5 degrees C, 25 minutes), but this did not decrease the incubation time required (at 37 degrees C) for completion of the normal reaction. In appropriate sera, the occurrence of normal and degenerative acrosome reactions in motile sperm was significantly separated in time to study the reactions independently. The duration of the normal reaction, i.e., the time between the first morphological change in the acrosome (initiation)until the actual detachment of the cap (termination) was estimated to be 20 minutes. Saline dilution of these sera delayed initiation of the reaction and increased the duration of the reaction  once it had started. Data from cold-shock and serum dilution experiments indicate that the mechanisms which govern the initiation and termination of the normal reaction are independently variable, and further suggest that initiation involves a change in membrane permeability and that termination includes membrane vesiculation.


The development of the oxygen permeability of the avian egg shell and its membranes during incubation.

The 02-permeability of the avian egg shell and shell membranes is initially low (approximately equal to 0.1-10(-6) ml O2 STP-sec-1cm-2-mmHg-1) during incubation but increases about 10-fold after the first week. This increase correlates with a decline in water content of the membranes. A major increase in colloid osmotic pressure (up to 50 cm Hg) occurs and is the suggested cause for the onset of rapid removal of water from the membranes. A high membrane water content correlates with low O2-permeability and vice versa. The final degree of membrane hydration reached during incubation is independent  of ambient humidity; that is, the O2-permeability of the shell and its membranes is controlled by conditions inside the egg. An hypothesis is presented to explain the profound increase in O2-permeability while the rate of water loss from the egg remains stable during incubation. The removal of water from the shell membranes by the increased colloid osmotic pressure will increase the number of gas filled channels in the membranes which in turn will increase the O2-permeability. In spite of the change in water content, the water vapor pressure in the shell membranes will always be very close to that of a free water surface and water loss will hence be determined by the ambient humidity and the porosity of the mineral shell.


Epithelial stratification in the developing chick cornea.

The process of epithelial stratification was studied in the embryonic chick corneal eipthelium between 10 and 21 days of incubation. Information was collected on the DNA synthetic activity occurring in individual cell layers, on cell density changes in the basal layer, and on mitotic spindle orientation in each cell layer before, during, and upon the completion of alyer formation. Prior  to the initiation of stratification, mitotic spindles are oriented parallel to the basement membrane interface. This orientation changes to predominantly vertically directed spindles as layer formation proceeds. Later, the majority of the spindles are horizontally aligned once more. This pattern was observed as each successive cell layer formed. The possible relationship between the spindle data and that obtained on DNA synthetic activity and cell density changes is discussed in terms of the role these factors might play in layer formation in the cornea, as well as in other stratified epithelia.


DNA synthesis during the development of the chick cornea.

The frequency and pattern of DNA synthesis were analysed autoradiographically in the developing chick cornea. Each cellular population was studied in time-sequence fashion from the time of its appearance until hatching. There is a sharp drop in the synthetic index (number of labeled cells/total number of cells) in the anterior corneal epithelium soon after its formation, corresponding in time to the secretion of extracellular matrix material by this tissue. A similar decrease does not occur in adjacent tissues. Continous labeling experiments show that about 20% of the corneal cells are not in the proliferative pool at this time while 100% of the cells in the underlying lens epithelium and the surrounding head epidermis and head mesenchyme are labeled. Cell cycle measurements indicate that the proliferative kinetics of both the corneal epithelium and the head epidermis are similar at this time even though the percentage of labeled cells in each region differs. The formation of the corneal endothelium and the movement of fibroblasts into the stromal region are events which involve extensive cellular migration. Labeled cells are observed at all stages of both endothelial and stromal fibroblast migration, indicating that DNA synthesis occurs during the course of cellular migration in the developing cornea.


Cytophotometric study of nuclear proteins during embryogenesis in two nematode species, Ascaris lumbricoides and Panagrellus silusiae.

Patterns of nuclear protein changes during embryogenesis in two nematode systems: Ascaris lumbricoides and Panagrellus silusiae were examined microspectrophotometrically. In both species, development is accompanied by an extensive loss of basic nuclear protein as noted by the diminished intranuclear binding of both the Sakaguchi reagent and fluorodinitrobenzene chromophore. The alkaline fast green (pH 8.1) procedure stained both nuclear and cytoplasmic regions of interphase cells to a similar extent throughout embryogenesis. In cells at metaphase the chromosomes bound the fast green dye intensely while the cytoplasm continued to give a positive reaction. Relative Feulgen stainability of nuclei during embryonic development varied between species. In Ascaris, the one-celled stage nucleus was Feulgen-negative and the LI juvenile somatic nuclei yielded a mean Feulgen-DNA value which was considerably less than a postdiminution diploid DNA equivilent. In Panagrellus, the nuclei of one-celled stage embryos contain DNA in excess of a 4C quantity which subsequently is reduced during embryonic divisions. As in Ascaris the nuclei of Panagrellus LI juveniles give hypodiploid Feulgen-DNA values. The significance of these changes remains to be determined.


Cytophotometric analysis of basic nuclear proteins during gametogenesis in the free-living nematode Panagrellus silusiae.

The cytochemical staining characteristics of basic nuclear proteins during gametogenesis in both sexes of the free-living nematode Panagrellus silusiae were monitored by absorption microspectrophotometry. During spermatogenesis, the levels of both of the nuclear-bound Sakaguchi and 1-fluoro-2, 4-dinitrobenzene (FDNB) reagents per Feulgen-DNA content increase prior to meiosis and subsequently drop off during spermiogenesis. During oogenesis, the amount of Sakaguchi-protein to DNA ratio rises slightly whereas the FDNB-protein to DNA ratio undergoes a meagre decline. Since the oocyte of Panagrellus accumulates DNA in excess of a 4C DNA equivalent, the relative constancy of the ratio of basic nuclear protein content to DNA amount during oogenesis signifies that these proteins are being continously produced during oocyte maturation. After treatment with alkaline fast green (pH 8.1) the cytoplasmic and nuclear regions of the gonocytes of both sexes yield such an intense reaction that microspectrophotometric measurements could not be taken. The basis of the cytoplasmic staining reaction to the fast green (pH 8.1) dye was not determined. The rapid, highly deterministic programme of embryogenesis in Panagrellus may require a substantial stockpiling of basic nuclear proteins during oogenesis.


Testis specific phosphoglycerate kinase B in mouse.

Mammals possess two genetically distinct forms of phosphoglycerate kinase (PGK). Only the X-linked PGK-A isozyme is detectable by electrophoresis of somatic and ovarian tissues of the mouse and of most other eutherian mammals studied to date. The PGK-B isozyme is highly active in testes and epididymides which contain spermatozoa, as well as in semen. PGK-B activity is first detectable in testes of 22-day-old mice and shows rapid increase concomitant with germ cell proliferation until day 40,after which activity increases only slightly. Two allelic isozymes (F and S) in mice express equal enzyme activity and are inherited in an autosomal codominant manner. One is equally as heat stable as PGK-A; the other is heat labile. Two of the 33 strains tested express neither F nor S, but do express a faintly staining PGK band which is of slightly faster mobility than F and which is absent from the other stains. This may represent a third allelic isozyme of PGK-B with reduced enzyme activity.


X-ray induced inhibition of DNA synthesis and mitosis in internal tissues during the initiation of limb regeneration in the adult newt.

Left front limbs of adult male newts were given 2000r of X-irradiation at least four weeks prior to amputation of both forelimbs. Internal stump tissues were evaluated for the ability to incorporate 3H-thymidine and accumulate colchicine-blocked mitotic figures. In otherwise uninjured limbs, irradiation stimulated low levels of DNA synthesis which did not increase significantly after amputation. Thus, as soon as DNA synthesis increased significantly in normal limbs as a result of amputation, it was demonstrably higher than in X-rayed limbs. In general, mitotic activity in both groups reflected the DNA synthetic rates. Since others have shown that denervation at the time of amputation blocks subsequent mitosis in internal stump tissues yet allows normal levels of DNA synthesis for eight days, we conclude that X-irradiation and denervation prevent cell division in potential blastema cells by different mechanisms.


The role of extracellular material in chick neurulation. I. Effects of concanavalin A.

The distribution of extracellular material (ECM) in developing neuroepithelium of stage 8+ chick embryos was investigated using lanthanum nitrate. The temporal changes in the distribution of ECM was correlated with the ongoing morphogenetic movements. The most striking finding was that as the folds were about to meet, thick dense ECM appeared between leading edges. Concanavalin A inhibited neural tube closure by binding to cell surfaces and disrupting the usual distribution of ECM in developing neuroepithelium.


Male haploidy in rotifers: relative DNA content of nuclei from male and female Asplanchna.

In A. sieboldi mitotic nuclei of males had one-half the nuclear DNA content of those of females. Spermatocytes from testes had 1c DNA contents. These observations indicate that the male is haploid and that spermatogenesis is atypical and involves no reductional divisions.


Isolation and characterization of Agrobacterium tumefaciens mutants affected in the utilization of octopine, octopinic acid and lysopine.

Using an enrichment procedure, mutant strains of Agrobacterium tumefaciens were isolated that lacked the ability to utilize octopine as a nitrogen source. Of 55 such isolates, 44 were unable to utilize several amino acids; the remaining 11 strains were altered solely in their ability to utilize octopine, octopinic acid and lysopine. It is concluded that only the latter were plasmid mutations. Among them, there was a high, but no absolute, correlation with avirulence. All strains contained the T1 plasmid. All virulent strains showed active transport of octopine when they had previously been grown in medium containing octopine, whereas the avirulent strains failed to show such transport. All the virulent mutants induced tumours containing octopine. The results are discussed in relation to the hypothesis that the genes which code for the octopine synthesizing enzymes in the tumour are of bacterial origin.


Sodium-dependent growth and respiration of a nonhalophilic bacterium, Pseudomonas stutzeri.

Pseudomonas stutzeri (van Niel strain) requires Na+ for growth. Its growth rate was a sigmoidal function of Na+ concentration, being maximal and constant from 2 to 50 mM-Na+, and half maximal at about 0-5 mM-Na+. The relationship between cell concentration and Na+ concentration was non-linear; cell concentration increased abruptly when Na+ was greater than 0-3 mM. Accumulation of Na+ in the organism during growth was not detected. In the presence of K+, respiration was enhanced specifically by Na+. The respiration rate of the organism growing in the culture was a linear function of the growth rate when limited by the Na+ concentration, whereas the maximum rate induced by excess Na+ was independent of the growth rate.


Cell-wall composition and structure of yeast cells and conjugation tubes of Tremella mesenterica.

Cell walls prepared from vegetative yeast cells and from hormone-induced conjugation tubes of the basidiomycete Tremella mesenterica had similar compositions. Evidence was found for 1,3-alpha-glucan (yeast 38%, tube 25%), 1,3-beta-1,6-beta-glucan (yeast 33%, tube 48%) and chitin (both less than 3%) in the walls. The walls also contained xylose (5 to 7%), mannose (6%), glucuronic acid (approx. 2%), and traces of galactose. Protein amounted to less than 2% of the wall weight. The cell capsule was very insoluble and could not be removed from the cell wall. The conjugation hormone did not appear to exert its effect on cell shape by causing gross changes in wall composition.


Polyamines in bacteriophage phi W-14 and in phi W-14-infected Pseudomonas acidovorans.

Bacteriophage phi W-14 is sensitive to osmotic shock. It contain sufficient free putrescine, 2-hydroxyputrescine and spermidine to neutralize about 15% of the DNA phosphates. The alpha-putrescinylthymine residues of the DNA could neutralize a further 25% of the phosphates. Label is transferred from ornithine to the alpha-putrescinyl residues of phi W-14 DNA. The rates of polyamine synthesis in Pseudomonas acidovorans are increased by phi W-14 infection.


Salt-dependent haemagglutinating measles virus in S.S.P.E.

Two strains fo S.S.P.E. virus show both haemagglutinin and salt-dependent haemagglutinin. These properties are associated with distinct plaque forms within each strain. The existence of salt-dependent strains in wild-type measles virus suggests that they should be found in the early isolates of all strains of S.S.P.E.


Inhibition of influenza virus replication in tissue culture by 2-deoxy-2,3-dehydro-N-trifluoroacetylneuraminic acid (FANA): mechanism of action.

The neuraminidase inhibitor 2-deoxy-2,3-dehydro-N-trifluoroacetylneuraminic acid (FANA) inhibits the mutlicycle replication of influenza viruses in tissue culture. Influenza virus grown in the presence of FANA contains neuraminic acid on its envelope which then serves as receptor for other virus particles causing extensive aggregation. Thus, FANA inhibits influenza virus replication by preventing the enzymatic removal of neuraminic acid from the virus envelope.


Effects of interferon on the human clonal cell line, RSa: inhibition of macromolecular synthesis.

Multiplication of the human clonal cell line, RSa, is completely inhibited by human leukocyte interferon preparations. Synthesis of DNA and protein is markedly reduced in these cells in proportion to the concentration of interferon applied. Interferon treatment leads to accumulation of cells of an epithelial morphology which do not enter the division cycle. It is suggested that the growth inhibitory effects of interferon on RSa cells may result from these effects.


A small RNA virus with a divided genome from Heteronychus arator (F.) [Coleoperai Scarabaeidae].

Some properties of a small RNA virus isolated from larvae of Heteronychus arator [Coleoptera: Scarabaeidae] are described. The virus develops in the cytoplasm of gut and fat body cells and is 30 nm in diamter. The sedimentation coefficient of virus was 137S and the buoyant density was 1-33 g/ml. The single stranded RNA was isolated as two species which sedimented at 22S and 15S, corresponding to mol. wt. of 1-0 and 0-5 X 10(6) respectively. The base ratios of the two RNA species were 22 S: A=29-0, C=24-1, G¿-8, U=24-1; 15S:A=26-4, C=23-8, G=24-7, U=25-2. There was one major polypeptide, mol. wt. 40 000 and two minor polypeptides in the virus. The virus was infective for Galleria mellonella and some other insects, but was not infective for mice. No evidence was obtained to suggest that the two RNA species were present in different particles.


Recent life changes and outcome of prolonged competitive stress.

To test the predictive utility of subjects' recent life changes with regard to outcome of prolonged competitive stress, the authors studied racers (N = 25) in a long distance Alaskan sled race, the Iditarod. Rank order correlations between subjects' 1-year life change units (LCU) total and adjusted place of finish proved significant by both Kendall's and Spearman's Test. Thus, lowe LCU scores correlated with better performance and higher scores with poorer performance. Differences between subgroupings of the racers are considered. The work suggests that the usefulness of recent life changes assessment may be extended beyong physical illness, particularly in the study of response and adaptation to prolonged stress.


On the methods and theory of reliability.

This paper reviews the most frequently used and misused reliability measures appearing in the mental health literature. We illustrate the various types of data sets on which reliability is assessed (i.e., two raters, more than two raters, and varying numbers of raters with dichotomous, polychotomous, and quantitative data). Reliability statistics appropriate for each data format are presented, and their pros and cons illustrated. Inadequancies of some methods are highlighted. The meaning of different levels of reliability obtained with various statistics is discussed. This critique is intended for the reading professional and the investigator who has an occasional need for reliability assessment. Statistical expertise is not required and theoretical material is referenced for the interested reader. Necessary formulas for computations are presented in the appendices. A summary table of some suitable reliability measures is presented.


Psychological differentiation and psychotherapy.

Patient's level of psychological differentiation was studied in relation to patients' and therapists' evaluations of the initial psychotherapy session. The evaluations assessed two broad dimensions of the interaction which generally have been considered important for psychotherapeutic success and which have been found to be related to patients' psychological differentiation: namely, patients' and therapists' satisfaction with the amount of structure, and therapists' impressions of patients' appropriateness for therapy. Significant correlations were obtained between patients' psychological differentiation and both of these dimensions. However, two control variables, socioeconomic status and alcohol use, were also found to be related to these dimensions. When the effects of these variables were partialed out, the relationships with therapists' impressions of appropriateness disappeared, but the relationships with patients' and therapists' satisfaction with the amount of structure remained significant. The relationship of these findings to other studies of psychological differentiation and psychotherapy is discussed. Finally, the contribution of the present results to the choice of the most appropriate measure of psychological differentiation is noted.


The relationships of the process/reactive, paranoid/nonparanoid, length of illness, and length of hospitalization dimensions to schizophrenic abstract thinking deficits.

Attempts to determine whether the quality of schizophrenic thought disorder varies from one type of schizophrenic to another in earlier studies have been hindered by the contamination of the major individual difference dimensions with each other. In the project described here, partial correlations were run between each of two abstraction deficit measures (Proverbs Test Abstract Level and Autism scores) and four independent variables which represent dimensions commonly used as criteria in individual differences research in schizophrenia--Ullmann-Giovannoni Process-Reactive scores, the MMPI Paranoia Scale, length of illness, and length of hospitalization. In each correlation the three noncriterion individual difference measures, the unused abstraction measure, age, education, and WAIS Vocabulary were partialed out. The correlations were also corrected for attenuation. After partialing, level of abstraction was negatively correlated with processness. Autism was positively related to reactiveness and length of hospitalization. Neither of two paranoid/nonparanoid measures used nor length of illness was related to either dependent variable.


Factors compelling psychiatric hospitalization in crisis.

At a time in a large community mental health center when all adjunct facilities were geared for crises, the compelling determinants in those patients still requiring hospitalization were studied. It was found that all patients answered affirmatively to one or more of the following six categories as occurring in their prehospital life: 1) alcohol abuse; 2) other drug abuse; 3) suicidal attempt; 4) a recent loss; 5) stoppage (or reduction) of medication; 6) stoppage of outpatient treatment. It was found that those patients diagnosed schizophrenic (69 per cent) did not significantly differ in the number of affirmative answers given in each of the six categories when compared to the total patient population. The most frequent categories to which an affirmative answer was given were stoppage of medication and stoppage of outpatient treatment. There did appear to be a trend for various combinations of these categories in a give patients. The schizophrenic group tended to have more affirmative answers in combinations of categories 3 and 4. The importance of these findings in the hospitalization and follow-up treatment of psychiatric patients is discussed.


Prolonged LSD flashbacks as conversion reactions.

This paper presents a case study of the background and treatment of a patient with prolonged LSD flashbacks. The hypothesis that flashbacks can be psychologically determined symptoms is supported by the dynamics of the case and the course of treatment. A second focus is a partial explanation for the often made observation that obessive-compulsive personalities are at increased risk for LSD flashbacks.


Characteristics of the sympathetic innervation of the nictitating membrane and of the vasculature of the nose and tongue of the cat.

Vasomotor responses from the nasal mucosa and tongue, and contractions of the nictitating membrane, were recorded on stimulation of the cervical sympathetic or internal carotid nerves. Preganglionic sympathetic nerve fibres which elicited a membrane response possessed a lower threshold than those which evoked nasal vasoconstriction, while the latter displayed a lower threshold than fibres which evoked tongue vasoconstriction. The sympathetic vasodilator fibres to the tongue whose activity was revealed after alpha-receptor blockade, had a similar threshold to the vasoconstrictor fibres. Membrane contraction, nasal vasoconstriction and occasionally tongue vasoconstriction could be evoked by stimulating the internal carotid nerve. The postganglionic fibres innervating the nasal mucosa had a similar threshold to those of the nictitating membrane, which may indicate that there are small myelinated fibres innervating the mucosa. The preganglionic compound nerve action potential had four major components, S1-S4. S1, S2 and usually S3 fibres were associated with membrane contraction; S2, S3 and sometimes S1 fibres were associated with nasal vasoconstriction; and S3, usually S2 and occasionally S1 fibres were associated with vasoconstriction in the tongue. It is concluded that each of these three groups of nerve fibres, but not S4 fibres, may include fibres associated functionally with the three effectors. There was a considerable difference between the relative amplitude of the responses of the three effectors elicited by stimulation of the cervical sympathetic nerve at frequencies between 0.2 and 2 Hz. Vasoconstrictor responses were relatively larger than membrane contractions suggesting differences in the mechanisms of neurotransmission at the neuroeffector junctions.


[The embryonic pineal organ of Lacerta vivipara J. I. Differentiation of the cells of the sensory line (CSL). The gradient of morphological differentiation].

This paper deals with the cytological development of the cells of the sensory line (CSL) of the pineal organ in Lacerta vivipara J. from the embryonic stage 30 on to the third day after birth. The general results are diagrammatically represented in figure 29. Only from stage 35 on, a diversity of sensory line cells can be distinguished. During ontogenetic development, in the photoreceptor cells (P) secretory activity is not observed. From stage 38 on, the photoreceptive poles of these elements show a differentiation of disks while, from stage 37 on, their basal processes make synaptic contacts with dendritic outgrowths originating from intra-epithelial sensory nerve cells. The embryonic secretory rudimentary photoreceptor cells (SRP) are characterized by an intensive secretory activity. Our quantitative analysis reveals a highly significant increase, during ontogenetic development, of the number of dense secretory granules, stored in the basal processes of the SRP. The photoreceptive poles of the SRP, just like those of the P cells, show the differentiation of disks from stage 38 on. Only just after birth, the outer segments of the SRP become rudimentary. From the absence of characteristic synaptic contacts between the basal processes of the SRP and dendrites of the sensory nerve cells it is concluded that, during ontogenetic development, the SRP become rudimentary as photoreceptivity is concerned. During the ontogenetic development of the pineal organ in Lacerta vivipara, morphological signs pointing to regression of its photoreceptor function are not very marked. In showing a photoreceptive differentiation of the outer segments of the SRP, the present investigation agrees with phylogenetic studies by other authors and supports the concept of the presence of a sensory cell line in the vertebrate pineal organ (Collin, 1969 b).