Autotomy following peripheral nerve lesions: experimental anaesthesia dolorosa.

(1) When hindlimb peripheral nerves are cut across in rats and mice, there is a tendency for the animal to attack the anaesthetic limb. We have called this attack "autotomy". In this paper we describe the time course and degree of autotomy following various types of nerve injury. (2) Four different types of lesion were applied to the sciatic nerve of rats. The most serious autotomy was produced by section of the nerve and encapsulation of its cut end in a polythene tube. Section followed by immediate resuturing also produced serious autotomy. Simple ligation of the nerve end was followed by less autotomy than encapsulation or cut and resuture. A crush lesion caused only minimal attack. (3) Section of the saphenous branch of the femoral nerve produced no autotomy. However, if the saphenous and sciatic nerves were ligated at the same time so that the entire foot became anaesthetic there was a great increase of autotomy over that seen when the sciatic nerve alone was ligated. This increase with the double lesion occurred even if the saphenous nerve was ligated more than 100 days after the sciatic nerve had been cut. (4) Mice showed autotomy very similar to that seen in rats but the onset was somewhat faster. (5) Reasons are given to propose that autotomy is triggered by an abnormal afferent barrage generated in the cut end of the nerve. Autotomy from peripheral nerve lesions is a different phenomenon from that seen after dorsal root section. Autotomy occurs under conditions which produce anaesthesia dolorosa in man. This simple model may be suitable for studies of the prevention of irritations originating from chronic lesions of peripheral nerves.


Recent advances in the treatment of pressure sores.

The problem of decubitus ulceration is a common one in para- and tetraplegic patients. It is a problem which involves these patients spending long periods in hospital. In 1977 almost 50 per cent of the patients re-admitted to our Unit had skin problems. During 1977 the average time spent in our Unit with skin problems of all degrees, was almost 3 months. Over the past few years several new products have become available for cleansing and healing these sores which, it seems, may reduce the time required in preparation for surgery or in achieving healing. We discussed the application of these products and the results of their use in our hands.


Lipoprotein lipase activity in the skeletal muscle during physical exercise in dogs.

Changes in lipoprotein lipase activity /LPLA/ in the quadriceps femoris muscle were followed in ten dogs during 3-hour treadmill exercise and 2-hour post-exercise recovery period. During the first hour of exercise muscle LPLA steeply increased. Subsequently the enzyme activity tended to plateau. After exercise LPLA decreased to the pre-exercise value within 1 hour. It is concluded that exercise increases the ability of skeletal muscles to remove triglycerides from the circulation.


Epinephrine and the pacemaking mechanism at plateau potentials in sheep cardiac Purkinje fibers.

1. In 1.35 mM [K+]0, sheep cardiac Purkinje fibers depolarized to about -40 mV. Whereas some fibers oscillated spontaneously at plateau potentials, others could be made to oscillate when polarized by intracellular currents. Pacemaker activity at plateau potentials (-50 to 0 mV) was distinct from that caused by the iK2 pacemaker at more negative potentials (-60 to -100 mV). 2. Epinephrine induced spontaneously occurring action potentials and increased pacemaker activity in depolarized Purkinje fibers. The ED50 for the positive chronotropic effect of epinephrine was about 5 x 10(-7) M. This concentration is similar to that reported for the effect of epinephrine on plateau amplitude (Carmeliet and Vereecke, 1969) and the slow inward current (isi, Reuter, 1974). 3. In voltage clamp experiments, epinephrine, increased the magnitude of isi and of an outward plateau current, ixi. It is concluded that epinephrine effects pacemaking at plateau potentials by increasing isi and without shifting the voltage dependence of these currents. The onset of pacemaker activity by epinephrine was preceded by membrane depolarization that results from an inward shift of the steady-state current-voltage relation. This current may flow through isi channels that are activated but not completely inactivated.


The effect of harmaline on intestinal sodium transport and on sodium-dependent D-glucose transport in brush-border membrane vesicles from rabbit jejunum.

Harmaline inhibition of sodium uptake and of sodium-dependent D-glucose transport was investigated using brush-border membrane vesicles from frozen rabbit jejunum. Under sodium-gradient conditions, "initial" D-glucose uptake (20 s) was inhibited by harmaline at concentrations above 0.5 mM, but at lower harmaline concentrations D-glucose uptake was stimulated by 10--15%. When a similar potassium gradient was used, harmaline had no effect. At concentrations up to 2 mM, harmaline did not alter the equilibrium uptake of D-glucose or D-mannitol. After pre-equilibration with sodium (25 mM), G-glucose uptake was inhibited at harmaline concentrations ranging from 0.1 to 2 mM. Sodium (10 mM) uptake was also inhibited by harmaline. Increasing the sodium concentration reduced the inhibitory effect of harmaline on tracer sodium uptake as well as on sodium-dependent D-glucose uptake. Similar to phlorizin, harmaline (1 mM) was able to prevent glucose-induced sodium influx across the brush-border membrane. Sodium uptake into brush-border membrane vesicles seems to be inhibited at lower harmaline concentrations than sodium-dependent D-glucose uptake. At high (2 mM) inhibitor concentrations, however, sodium-dependent glucose uptake is more strongly inhibited than sodium uptake. These results suggest that harmaline inhibits both sodium and sodium-dependent transport across intestinal brush-border membranes by interacting with specific sodium-binding sites.


Periodic changes in blood flow in the in vivo rat kidney.

The frequency response of the blood flow through the rat kidney in vivo has been studied. A piston controlled by a random-signal generator compressed the abdominal aorta proximal to the renal artery eliciting stochastical arterial pressure changes of an amplitude of less than or equal to 5 mm Hg. This small amplitude allowed to study the system under physiological conditions. In accord with earlier results from isolated kidneys pressure induced maxima of flow resistance were found at 0.005 Hz and at 0.1 Hz, thus demonstrating that in vivo humoral and/or nervous factors do not significantly alter the renal vascular response to changes of arterial pressure.


Extracellular space determination in rat small intestine by using markers of different molecular weights.

The apparent extracellular space (ECS) of rat jejunum, everted and cannulated "in vitro", has been measured by using extracellular markers of different molecular weights. The markers used were two polyethyleneglycols, 14C and 3H labelled (14C-PEG MW 4000 and 3H-PEG MW 900) and 3H-sucrose. The ECSs for the mucosal and serosal sides have been separately determined throughout the time course, and it has been found that the two spaces are identical when PEG 4000 was used but the serosal ECS is almost the double when using PEG 900. The serosal ECS determined with sucrose is four times as big as the mucosal ECS. It seems reasonable to conclude that the best marker for the measure of total apparent ECS is sucrose, placed in the serosal compartment, taking into account that the mucosal ECS is four times smaller than the serosal one. All the markers used reach equilibrium with ECS, more rapidly in the mucosal than in the serosal ECS. Finally, by comparing cell water and cell Na concentrations, one observes that there is a statistical difference between the results obtained by using PEG 4000 as an extracellular marker and those obtained with sucrose.


The effects of pressure on the water permeability of the descending limb of Henle's loops of rabbits.

Descending limbs of Henle's loops from rabbits were perfused in vitro. Using techniques where the collecting pipets permitted cannulation of the tubule, we were able to maintain reasonable flow rates at lower perfusion reservoir heights than are required with a conventional "Sylgard seal" pipet. The bath was either isosmotic to the perfusate, or was made 300 mOsm hyperosmotic using urea. Net water reabsorption did not occur in tubules perfused at low pressure (average reservoir height = 26 cm H2O) even when the bath was hyperosmotic: delta Jv = -0.06 +/- 0.18 nl/min (n = 7). Observed increases in sodium concentration and osmolality of collected fluid, when the bath was made hyperosmotic, were 16 +/- 8 mM (n - 7) and 254 +/- 38 mOsm (n = 7), respectively. Presumably the large increase in osmolality of the collected fluid was due to entrance of urea. When the "Sylgard seal" collecting end was utilized higher perfusion reservoir heights had to be used to maintain flow (mean height 66 cm H2O). These tubules were highly permeable to water as reported by others for this tubule segment. In the presence of a hyperosmotic bath water extrusion resulted in a dramatic increase in the osmolality of the collected fluid (312 +/- 5 mOsm; 7 tubules) which was almost completely accounted for by an increase in sodium concentration (153 +/- 8 mmole/l; 6 tubules). The 14C urea permeability (measured lumen to bath) of descending limbs in a 300 mOsm bath was 0.64 x 10(-7) cm2 . s-1 +/- 0.23 x 10(-7) (11 tubules). When the bath was made hyperosmotic using urea or raffinose the 14C urea permeability increased significantly.


Renal blood flow distribution at varying perfusion pressure in the alloperfused dog kidney.

Tissue blood flow (TBF), its percent distribution and glomerular blood flow (GBF) were measured using labelled microspheres 15 micrometer in diameter (M) and chicken red blood cells (CRBC) at perfusion pressures (PP) of 17.3, 12.8 and 8.0 kPa (130, 95 and 60 mm Hg) in isolated alloperfused dog kidneys. Renal blood flow (RBF) was never interrupted during the isolation. Experiments with M showed a marked inequality of the tissue blood flow in different parts of the renal cortex at a constant PP of 17.3 kPa. TBF was highest in the outermost quarter and lowest in the juxtamedullary one. Using CRBC, a homogeneous TBF was observed in the outer 3/4 of the renal cortex with a lower flow in the innermost quarter. With M, a typical percent "redistribution" of TBF and GBF into the inner cortical regions was indicated during PP reduction. With CRBC, this phenomenon was observed only at PP below the range of RBF autoregulation (8.0 kPa) and was much less conspicuous than with M. The smaller size and higher elasticity of CRBC as compared with M, may result in a more realistic reflection of cortical blood flow distribution. The GBF of outermost superficial glomeruli decreases, even with CRBC, with each PP reduction, the difference exhibiting only a 5% significance level. The lower limit of BF autoregulation in these glomeruli seems to be somewhat higher than that of total RBF autoregulation.


Autoregulation of superficial nephron function in the alloperfused dog kidney.

Isolated dog kidneys were each pump-perfused by another dog during 4 experimental periods at perfusion pressures (PP) of 21, 17, 13, and 8 kPa, resp. (i.e. 160, 130, 94, and 60 mm Hg). At the 3 highest PP values, the total kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were perfectly autoregulated while at the lowest value both values were significantly lowered. No significant difference was observed between the single nephron GFR (SNGFR) of periods 1 and 2; in period 3 (PP = 13 kPa) a lower value was observed (P less than 0.05). Free flow pressure in proximal convolution (FFP), stop-flow pressure (SFP), and peritubular capillary pressure (PCP) were not different in period 2 than in period 1, but were significantly lower in period 3 (P = 0.02--0.05). Effective filtration pressure (EFP) was the highest in period 1, decreasing significantly with decreasing PP. Filtration pressure equilibrium was observed in period 4 at PP 8 kPa. Total blood flow resistance (RT) fell with decreasing PP, the drop being due to a steep decline in afferent resistance (RA). Efferent resistance (RE) increased as PP decreased. Ultrafiltration coefficient (Kf) rose with declining PP both within and outside the autoregulatory range. The results indicate that the lower limit of autoregulation is higher in superficial nephrons than in the whole kidney.


Exogenous and endogenous stimulations during different phases of pancreatic secretion in conscious rats.

The effects of stepwise increasing doses of intravenous caerulein, secretin, urecholine and intraduodenal oleic acid were investigated in conscious rats. a) Basal water, bicarbonate, and protein secretion significantly augmented after diversion of pancreatic juice. On the basis of protein secretory pattern of basal secretion 3 stable stages have been recognised: 1. The most physiological basal stage during return of pancreatic juice. 2. The first, highly elevated plateau from the 4th to 7th 30-min period after diversion of pancreatic juice. 3. The second, delayed and less elevated plateau after 270 min. b) The following patterns of stimulated secretion were observed: 1. Caerulein stimulated protein and bicarbonate secretion during return of juice and the first plateau but it failed to elicit a significant response during the second, delayed plateau. 2. Secretin and urecholine showed similar protein responses during return of pancreatic juice but after diversion, they stimulated water and bicarbonate secretion only. 3. During the second plateau oleic acid stimulation resulted in a significant increase in water and bicarbonate secretion but no significant increase occured in protein output. The delayed inhibition of protein secretion, previously described in our laboratory, was unchanged. 4. Supramaximal doses of exogenous stimuli caused an inhibition in pancreatic secretion.


Measurements of the perivascular PO2 in the vicinity of the pial vessels of the cat.

PO2's in the environment of the pial micro-vessels of the cat were measured using recessed tip oxygen microelectrodes. Measurements were made on the surface of vessels with internal diameters ranging from 200 micrometers to 22 micrometers. Blood oxygen partial pressures were also measured inside these vessels by penetrating the vessels with sharpened electrodes. Both intravascular and extravascular PO2 values decreased progressively from the large arterial vessels down to the small arterioles. The observed values of intravascular PO2 showed a systematic longitudinal decrease from 98.5 +/- 10.7 (SEM) mm Hg in the largest vessels down to 72.6 +/- 3.6 mm Hg in the smallest vessels. In addition to the longitudinal gradient, a transmural gradient was observed across the walls of the microvessels. The difference between blood PO2 and vessel surface PO2 was 27.0 +/- 2.5 mm Hg in the largest vessels and 6.0 +/- 2.2 in the smallest. The mean wall thickness in these groups of vessels were 27.0 +/- 1.5 and 7.5 +/- 0.8 micrometers respectively. Measurements of the minimum tissue PO2 on the exposed surface of the cortex yielded a value of 25.4 +/- 6.6 mm Hg. Systemic arterial partial pressure of oxygen averaged 94.7 +/- 4.7 mm Hg. The data indicate that significant gradients for oxygen exist both longitudinally and radially in association with the pial vessels. The longitudinal gradients represent losses of oxygen from the precapillary vessels. The transmural gradients are apparently the result of both consumption by the microvessel wall and diffusional gradients due to oxygen flux into the extravascular space.


Interaction of adenosine and its phosphorylated derivatives with putative purinergic receptors in the gill vascular bed of rainbow trout.

1. The haemodynamic responses of trout gill to pulses of adenosine and related nucleotides were recorded in isolated trout head preparations. 2. Pulses of adenosine and related nucleotides induced a vasoconstriction of arterial gill vessels. Theophylline antagonized the resonse to adenosine but had not influence on its metabolism. 3. Dipyridamole and two adenosine deaminase inhibitors [deoxycoformycin and erythro-9(2-hydroxy-3-nonyl) adenine] had no effect on either the haemodynamic response of adenosine or its deamination and its uptake by gill tissues. 4. The adenosine response was neither mediated by cholinergic nor adrenergic receptors. 5. These results suggest the existence of extracellular "purinergic receptors" in the gills of trout.


A comparison of the stimulus-response curves of aortic and carotid sinus baroreceptors in decerebrated cats.

Recordings of total nerve activity suggested differences in the sensitivities and working ranges between aortic and carotid sinus baroreceptors. This result however, conflicts with single fibre studies from isolated receptor zones. Thus it appeared of some interest to compare the function curves of aortic and carotid sinus baroreceptors in the intact animal. This was achieved by comparing the response characteristics of two groups of aortic and carotid sinus baroreceptors in decerebrated cats. One smaller group consisted of 11 receptor pairs, each member of the pair being studied simultaneneously in the same cat, and a larger group consisting of 98 aortic and 49 carotid sinus baroreceptors studied independently of each other. The response of each receptor to wide pressure variations was recorded by inflating and deflating an intraaortic catheter tip balloon. Function curves were derived by plotting receptor discharge in terms of spikes per second against mean aortic pressure. No significant differences were found either in the slope of the function curves or their mean pressures at minimum activity, the latter appearing to be set by the working blood pressure level. Thus it was concluded that aortic and carotid sinus baroreceptors differ neither in their sensitivities nor in their working ranges when in their physiological environment.


Effects of glucose and ouabain on transepithelial electrical resistance and cell volume in stripped and unstripped goldfish intestine.

1. In goldfish intestine (perfused unstripped segments and mucosal strips) the serosal addition of ouabain (10(-4) M) resulted in a vanishment of the transepithelial potential difference and in a continuous increase in transepithelial resistance. 2. Incubation of mucosal strips with ouabain resulted in an increase in sodium content which was greater than the decrease in potassium content. The resulting increase in cation content was accompanied by an increase in chloride content and an increase in water content. 3. Histological examination showed that exposure to ouabain resulted in a swelling of the epithelial layer as compared to the control situation. 4. The ouabain induced resistance increase is greater in the presence of glucose, 3-OMG or fructose than in the presence of mannitol. Phlorizin (10(-4) M) inhibits the extra resistance increase induced by mucosal glucose but is without effect on the fructose induced extra resistance increase. The initial velocity and the magnitude of the glucose induced extra resistance increase depends on the glucose concentration. 5. The results suggest that in goldfish intestine ouabain induces cellular swelling with a concomitant collapse of the lateral intercellular spaces, which is the cause of the increased transepithelial resistance. The additional changes in resistance induced by sugars suggest that the cell membrane is more permeable to glucose, 3-OMG and fructose than to mannitol. The resulting changes in osmotically active material within the epithelial cell influence the cross-sectional area and consequently the conductivity of the paracellular shunt pathway. The hypothesis that these sugars do not induce a resistance change in the absence of ouabain is discussed.


A slow-release technique for inducing prolonged paralysis by tetrodotoxin.

A technique is described for the slow-release of tetrodotoxin in peripheral nerves using a constriction capillary. The capillary, which was implanted under the epineurium of the sciatic nerve, released tetrodotoxin from a 25 micrometer pore. Nerve block was complete after approximately 20 min and lasted 6--9 days. Replacement of the capillary enabled paralysis of the rat hindlimb to be maintained for periods of 21 days and longer. Studies with radioactively labelled compounds demonstrated that the efflux rate from the capillary was dependent on the size of the pore and the relative molecular mass of the compound.


A kinetic model for the muscarinic action of acetylcholine.

The timecourse of the membrane hyperpolarization evoked by stimulation of postganglionic parasympathetic nerve endings in isolated atria from the guinea-pig heart is mainly governed by two exponentials, one describing most of the rising phase (rate constant k alpha = 2.88+/-1.135 s-1) and one which completely describes the decline of the response (k beta = 0.58+/-0.31 s-1). An exact description of the muscarinic receptor mediated potential change, which also allows for its apparent latency and its s-shaped beginning, is found if two additional faster exponentials are introduced. In agreement with earlier results a model of four consecutive reactions is presented. It is concluded that during muscarinic cholinergic transmission reactions subsequent to binding of the ACh-molecules to the receptor are rate-limiting.


[Female hyperprolactinaemia. 19 cases (author's transl)].

The authors were able to confirm the ineffectiveness of vitamin B6. The correction of hyperprolactinaemia by bromocriptine restored ovarian function immediately, or after the failure of surgical treatment. It would still be premature to determine the exact place of surgery in this type of pathology.


Atropine stereotypy and its inhibition by intracaudate triperidol in the rat.

One component (rearing) of the stereotyped behavior of the rat was quantitated using erigometer, a new device developed in this laboratory. Intraperitoneal injection of atropine, but not methylatropine, caused dose-related stereotyped behavior in the rat and this effect was antagonized by intracaudate injection of triperidol in a dose-related manner. It is concluded that stereotypy can be evoked also in the case when the striatal dopaminergic tone is normal or even below normal: it is the equilibrium of the striatal cholinergic-dopaminergic systems which must be shifted towards dopamine, which is necessary for the development of this behavioral manifestation.


Behavioral effects and cerebral pharmacokinetics of apomorphine in the rat: dependence upon the route of administration.

Effect of the route of administration and satiation on behavioral effects of apomorphine and its pharmacokinetics in the brain was studied in the rat. The highest brain concentration and the strongest behavioral response (gnawing) were observed after a subcutaneous injection of the drug to fasted rats. Intraperitoneal injections produced a more rapid onset of apomorphine action, but lower cerebral concentration of the drug. Intracerebroventricular injections produced a weak effect. Apomorphine administered systemically was eliminated from the brain according to equations for a two-compartment model; the possibility that the long half-time compartment represents the receptor bound apomorphine is discussed. After intracerebroventricular injections apomorphine was eliminated according to equations for the one-compartment open model: the elimination of the drug from the cerebrospinal fluid to circulation was rapid (half-time approx. 9 min).


Influence of lesion of the median raphe nucleus on motility and dopamine turnover.

Both the spontaneous locomotor activity and the locomotor activity stimulated by apomorphine are enhanced in raphe lesioned animals. The exploratory activity does not show clearcut differences. After unilateral microinjection of dopamine into dopaminergic areas intensity of rotation and dominance of direction are amplified in lesioned animals. Other regions fail to evoke asymmetric or enhanced motoric reactions. The sensitivity of the dopaminergic system of raphe lesioned animals is increased too against unspecific stimulation, but with less strong dominance of direction. The general enhancement of motor activity reflects the inhibitory influence of the serotonergic system. In parallel to the change of behavior we observed a moderate increase of dopamine content connected with an accelerated turnover in lesioned animals.


Interaction of fibrinopeptides A and B with dopaminergic receptors in central nervous system.

The effect of fibrinopeptides A and B (FAB) on the action of compounds affecting the dopaminergic receptors in central nervous system (CNS) of rats was investigated. These peptides given intraperitoneally (ip) or intraventricularly (ivc) exerted dose-dependent stimulatory effects on the CNS: Enhanced the apomorphine and amphetamine-induced stereotypies and reduced the catalepsy induced by haloperidol. FAB depressed the dopamine level, especially when given together with alpha-MT, and elevated the level of homovanillic acid in the striatum. The results suggest that the stimulatory effects of FAB depend on their interaction with dopaminergic receptors in the CNS.


[Andrological characteristics in males with X-chromosomal pathology].

The authors examined 32 patients with Klinefelter's syndrome: 21 with chromatine-positive (the 1st group), 11 with chromatine-negative (the 2nd group). In contrast to the patients of the 2nd group an altered karyotype was revealed in patients of the 1st group (47/XXY, 46XY/47XXY, 48XXXY/49XXXXY). Hormonal examination revelaed hypoandrogenia with a relative hyperestrogenuria in the majority of the patients of the 1st and 2nd groups. However, patients of the 2nd group displayed a greater preservation of the reserve testicular function. Further clinical, endocrinological and cytogenetic studies of the Klinefelter's syndrome is necessary for its differential diagnosis and correction.


[Aldosterone and progesterone content and blood renin activity in women with idiopathic edema syndrome in various phases of menstrual cycle].

Aldosterone and progesterone content and renin activity were studied by the radioimmunological method in women with the idiopathic edema syndrome and in healthy women in various phases of the menstrual cycle. The most significant differences were revealed in the luteinic phase of the cycle. A parallel elevation of the renin activity and of the aldosterone level against the background of a high progesterone level occurred in healthy women at this phase. Patients showed greater increase in the aldosterone level with the reduction of renin activity and a low progesteron level. Hyperaldosteronism was observed in patients with the idiopathic edema syndrome in all the phases of the cycle. It is suggested that an excessive elevation of the aldosterone level and a decrease in the progesterone level in the luteinic phase of the cycle could served as one of the pathogenetic mechanisms of the edema syndrome formation.


[Effect of glucocorticoids on the level of transcortin-like cytoplasmic receptors].

Experiments were conducted on intact, adrenalectomized and stress-subjected male Wistar rats; the level of transcortin-like cytosol receptors of the lungs heart, kidneys, and the liver was studied by means of 3H-corticosterone and solid-phase sorption. The level of transcortin-like receptors in the cytosol of various tissues in intact rats had the following declining sequence; the lungs, heart, kidneys, liver. In stress the level of transcortin-like receptors in the tissue cytosol displayed a sharp reducion, although the sequence characteristic of intact animals persisted. In adrenalectomized rats stress induced no significant fall in the content of transcortin-like receptors in the tissue cytosol, whereas intraperitoneal administration of cortisol to adrenalectomized rats decreased the level of these receptors. A hypothesis was put forward on the antistress action of transcortin-like cytoplasm receptors.


The effect of external stimulus change on ethanol-produced dissociation.

Rats which were subjected to aversive Pavlovian conditioning while in a state of ethanol-produced intoxication showed significantly less conditioned suppression of water drinking in the non-drugged state only if the external stimulus situation was also changed between conditioning and testing. This interaction between internal and external stimulus change supports a generalization-decrement explanation of drug-produced dissociation of memory. The number of conditioning trials was also manipulated, but this variable had no significant effect on the conditioned responses. In a second experiment, ethanol injections were given again shortly before testing. This treatment caused a normal degree of conditioned drinking suppression in rats conditioned in the ethanol state, indicating that state-dependent learning was responsible for the conditioned response deficit seen in the first experiment. The dissociation was asymmetrical since rats injected with ethanol before testing only showed a high degree of conditioned suppression.


[Endocrine function of the ovaries of blue foxes (Alopex ladopus) during postnatal ontogenesis].

Progesterone, androgen and estradiol levels in the blood plasma were radioimmunologically studied in female Alopex lagopus aged 2 to 9 months with different weight at birth. The blood sex steroid level showed a sharp elevation at the age of 4 months. The weight gain stops by this time. Thus, by the age of 4 months in females the sexual system becomes mature. From the age of 5 to 8 months there is a fall of the blood sex hormones, corresponding to anestrus, and by the age of 9 months there is a significant rise in the level of sex hormones pointing to activation of the ovarian function by the reproductive season. Large females had a tendency to earlier sexual maturation in comparison with the small ones. Since in the female animals of the species under study two peaks of sexual hormone concentration were revealed in the course of a year it is suggested that at the preceding evolutional stages representatives of the family were capable of reproducing twice a year.


A comparison of the effects of acute and subacute administration of beta-phenylethylamine and d-amphetamine on mouse killing behavior of rats.

beta-Phenylethylamine (PEA) is an endogenous amine that in some instances acts biochemically and behaviorally like amphetamine. In the present experiments, the effects of PEA on mouse killing by rats were compared and constrasted with the effects of d-amphetamine on this behavior. When given acutely to experienced mouse killing rats, PEA (16 and 32 mg/kg) inhibited killing in a direct dose dependent manner. This is similar to the dose dependent inhibition of killing by amphetamine reported previously. However, d-amphetamine but not PEA showed physiologic tolerance following 8 days of twice daily administration. Cross tolerance between the two drugs only occurred when d-amphetamine was administered subacutely. It was concluded that PEA and d-amphetamine have sililar acute effects but differed when given subacutely since PEA did not show tolerance and there was not bidirectional cross-tolerance. These data suggest that these drugs have different pharmacologic actions when given repeatedly. One possible difference may be the duration of action.


The involvement of interoceptive factors in the maintenance of heroin-seeking behavior.

The role of interoceptive stimuli in conditioned heroin-seeking behavior was investigated using forty-two naive male Wistar rats. A 21-day Phase I period in which 28 animals self-injected heroin in saline solution was followed by a 5-day Phase II period in which 7 animals were allowed access to the original solution; 7 animals were allowed access to saline only; 7 animals were allowed access to distilled water; and 7 animals were allowed no access to any solution. Results showed that only the heroin and (heroin-associated) saline groups shows a significant difference in operant rate compared to animals that had been continually exposed to saline only. It was concluded that heroin-seeking behavior was maintained in the (heroin-associated) saline group as a result of physiological conditioning following repeated association of saline with heroin.


Memory storage impairment or retrieval failure: pharmacologically distinguishable processes.

The effects of reserpine and syrosingopine on retention of a passive avoidance task in mice were investigated. Following repeated exposure to the training apparatus, the amnesia induced with syrosingopine could be reversed, the amnesia induced with reserpine could not. The amnesia produced by these agents was still evident 35 days following training. The results were discussed in terms of the effects of these drugs on memory consolidation and/or retrieval.


Annual differences in daily variations in hepatic drug metabolizing enzyme activity and plasma hormone levels in the rat.

Daily variations in hepatic drug metabolism and in plasma corticosterone and insulin levels were examined at monthly intervals over the duration of 1 year. Annual differences were observed in the basal levels of all parameters. Consistent daily variations were observed only in plasma corticosterone levels, whereas daily variations in each of the other parameters occurred inconsistently over the year with significant variations being found in ethylmorphine metabolism and insulin levels only five times, and in aniline metabolism, six times. These data show that daily variations in the parameters examined do not occur in a regular manner.


Corpus luteum susceptibility to prostaglandin F2 alpha (PGF2 alpha) luteolysis in hysterectomized prepuberal and mature gilts.

The susceptibility of induced corpora lutea (CL) of prepuberal gilts and spontaneously formed CL of mature gilts to prostaglandin F2 alpha (PGF2 alpha) luteolysis was studied. Prepuberal gilts (120 to 130 days of age) were induced to ovulate with Pregnant Mare Serum Gonadotropin and Human Chorionic Gonadotropin (HCG). The day following HCG was designated as Day 0. Mature gilts which had displayed two or more estrous cycles of 18 to 22 days were used (onset of estrus = Day 0). Gilts were laparotomized on Day 6 to 9, their CL marked with sterile charcoal and totally hysterectomized. On Day 20, gilts were injected IM with either distilled water (DW), 2.5 mg PGF2 alpha or 5.0 mg PGF2 alpha. An additional group of prepuberal gilts was injected with 1.25 mg PGF2 alpha, a dose of PGF2 alpha equivalent, on a per kilogram body weight basis, to the 2.5 mg PGF2 alpha dose given to the mature gilts. The percentages of luteal regression on Day 27 to 30 for mature and prepuberal gilts given DW, 2.5 mg PGF2 alpha and 5.0 mg PGF2 alpha were 0.0 vs 4.4, 43.5 vs 96.8 and 47.7 vs 91.6, respectively; the percentage of luteal regression for the prepuberal gilts given 1.25 mg PGF2 alpha was 75.1. These results indicate that induced CL of the prepuberal gilt were more susceptible to PGF2 alpha luteolysis than spontaneously formed CL of the mature gilt and that pregnancy failure in the prepuberal gilt could be due to increased susceptibility of induced CL to the natural luteolysin.


The effect of doxorubicin on hepatic and cardiac glutathione.

The effect of the antitumor antibiotic doxorubicin on glutathione and glutathione disulfide levels in mouse heart and liver has been evaluated. The glutathione content of hepatic and cardiac tissue from saline-treated controls exhibited a statistically significant diurnal variation. Doxorubicin administration produced a dose-related decrease in hepatic glutathione which was not blocked by pretreatment with the free radical scavenger alpha-tocopherol; a lesser drop in cardiac glutathione was also documented. These changes may play an important role in the metabolism and toxicity of doxorubicin.


A simple ballistocardiographic measure (IJ/HI amplitude ratio) in relation to electrocardiographic evidence of ischaemic heart disease.

A series of eighteen monozygotic and thirteen dizygotic twin pairs originally selected in 19=7--1968 because of the presence of symptoms of ischemic heart disease in at least one of the pair members was subjected to after examination including ultra-low frequency ballistocardiography. The ratio between IJ and HI amplitudes in the ballistocardiogram was used as an index of myocardial mechanical function. The IJ/HI ratio had a repeatability coefficient of 0.82 before and/or after psychiatric interview. The mean ratio did not change significantly after psychiatric interview. The measure was demonstrated to be independent of height, weight, age, heart rate and systolic and diastolic blood pressure and negatively correlated with a measure of somatic anxiety. The ratio was highly significantly correlated with electrocardiographic evidence of ischemic heart disease. The IJ/HI ratio showed a better discrimination than qualitative readings according to Starr and furthermore has the advantage of providing a continuous measure. The ratio seemed to be more influenced by the functional state of the myocardium than by genetic factors.


Development of sequence specific radioimmunoassay of human parathyroid hormone and its use in the diagnosis of hyperparathyroidism.

Two antisera which were raised against bovine parathyroid hormone (bPTH), and which cross-reacted with the human hormone, have been characterized. The antisera which originated from rooster and guinea-pig, were found to contain several populations of antibodies directed against both N-terminal and C-terminal sequences of the hormone. However, at proper dilutions the rooster antiserum did not bind the N-terminal fragment nor could this fragment displace the [125I] bPTH (1--84 amino acid residue) from binding to the antiserum. Furthermore, preincubation experiments with excess N-terminal fragment showed only a negligible reduction in maximal binding of the iodinated intact hormone using the rooster antiserum. In contrast, the guinea-pig antiserum reacted equally well with the N-terminal fragment and the intact hormone, and preincubation with this fragment reduced the binding of the [125I]bPTH (1--84 amino acid residues) by 75%. Gel filtration of hyperparathyroid serum on Bio-Gel P-60 showed immunoreactive material which was measured with both antisera, eluting at a position similar to the intact hormone. However, in the C-terminal specific, but not in the N-terminal specific radioimmunoassay the major component eluted together with or somewhat earlier than the N-terminal bPTH fragment (1--34 amino acid residue), and this peak represented more than 90% of total immunoreactive PTH (iPTH) in serum. This major iPTH component must therefore represent fragment(s) with intact carboxy-terminal sequences. The N-terminal specific radioimmunoassay was unable to measure iPTH in about 80--90% of healthy individuals while the C-terminal specific assay detected iPTH in about 88% of these sera (equal to or above 0.1 micrograms/l). Similarly, the N-terminal specific antiserum measured consistently lower serum iPTH concentrations in patients with primary hyperparathyroidism. In thirty-four out of forty-one patients with surgically verified primary hyperparathyroidism, serum iPTH concentrations equal to or above 0.60 micrograms/l were demonstrated using the C-terminal, specific radioimmunoassay.


The human body louse egg--correlative study of anatomy by SEM and light microscopy.

SEM and correlative light microscopy of the developing egg of the human body louse reveals a complicated aeropyle system within the operculum important for gaseous exchange. With SEM the opened nit shows three new structures: one, latch-like; a second, ellipsoid with spikes; and a third, pad-like with two parallel rows of pores. They are part of the surface membranes covering the developing embryo. The relationship of the pad-like structure to the ellipsoid structure with spikes is seen by tilting the specimen. The light microscopy findings help to understand the relationship of these structures, which to separate at the time of hatching. A theoretical model is proposed for the hatching mechanism. The latch consists of a clasp on a stalk which may act as a hinged lock when the operculum opens outward. The ellipsoid with spikes and pad appears to separate when the vitelline membrane is ruptured at the time of hatching.


Scanning electron microscopy of Spironucleus (Hexamita) muris infection in mice.

An epizootic disease characterized by failure to gain weight, lethargy, enteropathy, and death developed in weanlings from a production colony of NIH/Nmri CV mice. Light microscopic and scanning electron microscopic examination of the intestine revealed large numbers of protozoan parasites identified as Spironucleus (Hexamita) muris. The extensive, entangled mass of organisms in the intestinal lumen enveloped the villi and continued deep within the crypts of Lieberkühn. Inflammation and significant intestinal lesions were not observed. The scanning electron microscopic appearance of the small intestine in spironucleosis gives credence to a pathogenesis of malabsorption with subsequent, severe malnutrition and death in weanling mice.


Membrane events of fertilization in the sea urchin.

Four important events of fertilization in the sea urchin are: 1) the acrosome reaction of the sperm, 2) sperm-egg fusion, 3) the cortical reaction of the egg, and 4) the formation of the fertilization coat. The acrosome reaction is triggered by contact of the sperm with the jelly coat, a complex extracellular matrix surrounding the egg. This causes rapid fluxes of ions, fusion of the acrosome membrane with the plasma membrane, and extension of the acrosomal filament. The acrosome membrane inserted into thesperm plasma membrane covers the acrosomal filament and contacts the plasma membrane of the egg to initiate sperm-egg fusion. One consequence of sperm-egg fusion is insertion of the sperm plasma membrane into the egg plasma membrane, producing a mosaic patch. The sperm components inserted persist in development and can be identified by quantitative methods after gastrulation. Another consequence of sperm-egg fusion is the cortical reaction in which thousands of vesicles fuse with the egg surface, thereby adding their membranes to the egg plasma membrane and releasing their contents upon the egg surface. This results in an approximate doubling of the amount of membrane on the egg surface in a few seconds and produces a mosaic topography. The excess surface membrane is accommodated by elongation of egg microvilli. The cortical reaction causes a detachment of the egg glycocalyx or vitelline membrane, and this layer is elevated from the egg surface. Contents of the cortical granules combine with and alter the vitelline membrane by a hardening reaction to produce the fertilization coat. Hardening involves a peroxidase-mediated tyrosine crosslinking, requiring a burst of oxygen consumption by the egg to generate hydrogen peroxide and resulting in chemiluminescence. These events are followed by activation of metabolic processes in the egg and changes which protect the egg against polyspermy.


Complement consumption in the diagnosis of pigeon breeders' disease.

Two laboratory techniques have been applied for the diagnosis and follow-up of pigeon breeders' disease, viz. detection of precipitins against specific antigens from pigeon droppings and assays of human haemolytic complement (huC) consumption by pigeon dropping antigens. A simple laboratory test of huC consumption by pigeon antigens is described, revealing high huC sensitivity in almost all sera of pigeon breeders with manifest or former disease. False-positive results were seldom observed. Discontinuation of antigen exposure and/or corticosteroid therapy had no effect on the huC consumption level in the test system, despite precipitin titres falling below the level of detection. Titration studies revealed an initial decrease of the huC-consuming serum factors, but titres settled at a definite constant level, even after antigen avoidance for many years. Combined application of both the precipitin test and the huC consumption test appears to be a good procedure for the laboratory diagnosis of pigeon breeders' disease.


[Development of narcotics consumption in adolescents 19 and 20 years old. A comparison in the canton of Zurich 1971, 1974 and 1978].

In 1971, 1974 and 1978 representative samples of 19/20-year-old males and females in the Canton of Zurich (Switzerland) answered identical questionnaires on consumption of alcohol, tobacco and drugs. It was thus possible to analyze changes in consumption habits for alcohol, tobacco and drugs by young adults. Consumption patterns changed differently for males and females, with a tendency for females to approach the same levels as males. The number of persons who had been drunk at least once nearly doubled; among men to 68% (as compared to 41% in 1971) and among females to 44% (21%). However, the number of heavy alcohol consumers did not change greatly. The number of cigarette smoking males decreased markedly to 42% (compared to 55%) and is now similar to that of females (43%/41%). The consumption of drugs did not change strikingly. The number of females consuming marijuana increased slightly from 13% to 17%, whereas that of males decreased slightly to 20% (23%). This can be explained by the lower proportion of males with only 1--10 marijuana experiences. The social context of drug consumption shows greater changes than the mere number of consumers: the age of the first drug experience is now considerably lower while differences in drug contact by region or by social strata show a tendency to disappear, with the sole exception of persons without occupational training who now show extremely high drug experiences. It is therefore assumed that drug consumption is no longer a means of self-experience but rather a form of evasive behavior.


Structure and regeneration of the planarian basal lamina: an ultrastructural study.

The structure and regeneration of the planarian subepidermal basement membrane or basal lamina have been electron microscopically examined, particularly in relation to the changes of extracellular products at the wounded area. The intact basal lamina consists of three structural elements; namely, an electron-lucent zone, a limiting layer and a microfibrillar layer. Ultrastructural changes during wound healing have suggested that the amorphous material secreted in the interspace between the epidermal cells and blastema contains precursors of the basal lamina. Within the amorphous zone two distinct phases of the basal lamina regeneration are observed: one is a reconstitution of the limiting layer and the other is a polymerization of the microfibrils. The limiting layer arises from areas subjacent to newly developed hemidesmosomes of epidermal cells. The unit microfibrils are formed from an accumulation of the precursors through transitional smaller microfibrils. At the late stage, individual mature microfibrils are regularly lined with the limiting layer and cell membranes of the newly differentiated muscle fibres. On the basis of these observations we suggest that the planarian basal lamina is regenerated by the interaction between epidermal cells and myoblasts.


Ultrastructural observations on the granular leucocytes of the tuatara Sphenodon punctatus (Gray).

The granular leucocytes of an active, mature female tuatara, Sphenodon punctatus (Gray) were examined in the electron microscope. Eosinophils contained a lobulated nucleus, homogeneous, dense, irregularly shaped granules, assorted smaller granular inclusions, mitochondria and beta-glycogen. Endoplasmic reticulum, Golgi complexes and ribosomes were scanty. Immature neutrophils (myelocytes) were regular in outline and contained a compact nucleus. In the adjacent centrosomal region were paired centrioles with connected microtubules, and Golgi complexes. Ovoid electron-dense granules, mitochondria, lipid droplets and numerous microfilaments arranged randomly or in bundles, lay in the cytoplasm. Mature neutrophils were often highly irregular in outline, had a segmented nucleus and contained possibly a second type of granular inclusion. The basophils were regular in outline with a compact nucleus. Numerous ovoid homogeneous, electron-dense granules, mitochondria, beta-glycogen particles and some microfilaments were seen in the cytoplasm. The granules in many basophils appeared 'altered' or degenerate and most of these contained microtubules. The cytology of the granulocytes of the tuatara is compared with that in other vertebrates.


Follicle formation in the embryonic chick thyroid. III. Initiation of follicle formation.

It has been proposed that the follicular spaces in the thyroid form by either the coalescence of intracellular droplets or by separation of cell apices by secretion into the extracellular space. On the basis of examination of thyroid primordia in early chick embryos this study provides evidence that in the chick, at least, follicle formation conforms to the second model. The first indications of change in the chick thyroid is the appearance of interdigitations of the cell apices. These interdigitations form microvilli as the two surfaces become separated and the follicular space is established. Vesicles with two types of contents can be identified in proximity with the cell surface during follicle formation, but it is not clear if either the dense particulate or the more electron-lucid materials that they contain actually enter the follicular space. Neither removal of the pituitary gland by decapitation nor inhibition of collagen synthesis and a concomitant failure of the invasion of capsular mesenchyme prevents the initiation of normal follicle formation.


[Difficulties in the differential diagnosis of tuberculosis of the breast].

An analysis of the own material and of literature data permits to note alterations in the clinical course of mammary gland tuberculosis, which is the manifestation of tuberculosis pathomorphism under modern conditions. The lesion of the mammary gland is most commonly an isolated disease. This interferes with the differential diagnosis between tuberculous mastitis and tumors of the mammary gland and supports the opinion that the spreading of infection from other old tuberculous foci via hematogenic path plays the main part in the pathogenesis of tuberculosis of the mammary gland.


[Estrus induction in sheep injected with colostrum at different phases of the sexual cycle].

Investigations on the mechanism of colostrum effect in sheep sex apparatus stimulation were carried out. The experiments included 57 sheep, 10 of them used as a check and the remaining 47 distributed in four treatment groups and injected with colostrum at various phases of the sex cycle. It was established that the effectiveness of injecting cow colostrum on sheep with the aim of inducing synchronous oestrus during the regular reproduction season depends on the sex cycle phase at which the injection takes place. The effectiveness is higher in case injection is performed during the second half of dioestrum. The induced synchronous oestrus of sheep following colostrum injection is equivalent to the normal.


Distribution of four IgG Gm antigens in different experimental IgG samples.

The distribution of four Gm antigens was determined in rivanol-soluble as well as in chromatographically obtained human IgG preparations. In rivanol-soluble IgG, enrichment in IgG3 carrying Gm5 antigen was demonstrated and, in a preparation fractionated by DEAE-Sephadex chromatography, molecules with a predominantly Gml-expressed antigen were shown to be present.


Formaldehyde-related antibodies in hemodialysis patients.

In a study of anti-N-like antibodies, we tested sera from 93 hemodialysis patients for hemagglutination reactions with untreated and formaldehyde-treated reagent red blood cells. Six of 22 sera from patients who had been dialyzed with formaldehyde-sterilized membranes had anti-N-like activity and 20 (91%) specifically agglutinated formaldehyde-treated red blood cells. Sera from 71 patients dialyzed with disposable membranes neither had anti-N-like activity nor agglutinated formaldehyde-treated red blood cells. The agglutination of formaldehyde-treated red blood cells by sera from hemodialysis patients was unrelated to MNU phenotypes and, therefore, identified a second serologic specificity, provisionally termed "anti-formaldehyde." "Anti-formaldehyde" was absorbed by and eluted from NN red blood cells as well as from formaldehyde-treated red blood cells regardless of MNU phenotype. All eluates and sera containing anti-N-like activity also agglutinated formaldehyde-treated red blood cells, typically after the addition of anti-human serum. These findings are consistent with the hypothesis that anti-N-like reactions of hemodialysis patients' sera represent cross reactions of formaldehyde related antibodies with N antigens of normal red blood cells.


Reduced antibody response in patients with chronic renal failure undergoing hemodialysis with formaldehyde sterilized units.

In an attempt to explain the relatively low incidence of antibody production seen in patients undergoing regular hemodialysis, sera from 200 patients were exposed to formaldehyde under conditions similar to those during dialysis. It was found that this procedure substantially reduced antibody titers, except when the initial titer was very high. The danger of missing low antibody titers after dialysis is pointed out.


[Keeping quality of hard boiled eggs].

Only a few and contradictory results are available on the storage stability of hard boiled eggs which are of considerable importance for institutional feeding. Therefore four storage experiments on about 500 hard boiled eggs each were carried out and chemical and sensorial changes occurring during storage investigated. The one-day-old eggs of the same origin were boiled for 17 minutes under standard conditions and subsequently stored in air at a relative humidity between 73 and 85% at 4 degrees C (experiment No. 1), at 20 degrees C (experiments No. 2 and 3) and in pure carbon dioxide at 20 degrees C (experiment No. 4). Immediately after boiling, the eggs used for experiments No. 3 were dipped into coloured resin for egg shells (natural Manila-Kopa; dissolved in ethanol and stained with "Acillantechtgrün). Losses in weight during storages were distincly lower in the lacquered eggs than in the non-lacquered samples otherwise treated in the same manner. The weight decrease caused by the loss of water was extraordinarily high in pure CO2 and is due mainly the the decrease of the pH in the egg whites caused by the uptake of CO2. A few days after boiling the concentration of the free amino acids reached approximately the same level in albumen and yolk and remained practically constant over the following 3 weeks. For the breakdown of lecithine in yolk determined according to Grossfeld and Peter, a "deterioration quotient" of 6, like in unboiled eggs, was fixed as the limit value for unspoiled condition. Accordingly a possible storage time of 3 to 4 weeks resulted for the eggs stored at 4 degrees C and for the eggs treated with stained resin. The non-lacquered eggs stored in air or in CO2 at 20 degrees C reached the critical value in about 10 days. From the vitamins A, B1 and B2 only vitamin A showed considerable losses during storage. On the basis of the microbiological (3) and chemical findings and of the sensorial evaluation of colour, consistency, odour and taste of egg whites and yolks, the following storage times were determined for eggs in the quality class "saleable" requiring an overall rating not lower than 6 (satisfactory): 14 to 16 days, for non-lacquered eggs stored at 4 degrees C and for lacquered eggs at 20 degrees C whereas 5 days were found to be the maximum storage time for untreated eggs stored at 20 degrees C. If boiled eggs are stored in pure carbon dioxide at 20 degrees C, a distinct quality loss is observed already after a few days.


Is the aeration of the lungs a reliable sign of live birth?

One of the most important medico-legal questions is whether an infant was born alive or not. The aerated lungs do not mean in every case that the newborn had taken a breath. Under various conditions the aerated lungs may turn into unaerated ones and, on the other hand, a stillborn's lungs may seem aerated. The critical evaluation of the histological and macroscopical examinations may aid in solving the question.


[Effect of alcohol on cerebral cortex neurons].

Prevalent in the early period (10th--20th days) of experimental alcoholic intoxication were functional changes of the neurons and the dendrites with elements of compensatory character. With the progress of the pathological process (in 2,4,8,12, and 15 months) these functional changes gave more and more place to dystrophic and destructive ones. The following sequence of the dendrite structural changes was observed: a diminution of the number of impregnated spines, the loss of the spines, a convoluted pattern of the dendrites, a thinning of the dendrite branches with non-uniformity of their impregnation, appearance of "light fenestrae" along the dendrites. The damage of the dendrite structure plays an important role in the pathogenesis of alcoholic affections of the brain.


The influence of postnatal nutrition on lipoprotein lipase activity and hormone sensitive lipolysis in vitro of rat adipose tissue.

In rats grown up in small and large nests the lipolytic activity of adipose tissue was studied in vitro in dependence on age. Independent of age and sex a significantly higher lipoprotein lipase activity as well as a lower basal or norepinephrine stimulated lipolysis and reesterification (absolute) occurred in rats from small nests compared with rats from large nests. The calculated degree of reesterification was independent of the nest size, but decreased from 80% to 30% from one month to one year of age. The marked differences in the lipolytic activities of adipose tissue emphasize the distinct influence of the post-natal nutrition on metabolic functions in the later life and lead to the conclusion that the metabolism of adipose tissue of animals from small nests is directed towards a long-term increased storage of lipids.


Platelet turnover and megakaryocytopoiesis in ITP.

Among patients with ITP, a group of 9 subjects displayed a reduced platelet turnover. In their bone marrow the megakaryocyte mass was measured by 59Fe, and the results were referred to those of 6 patients with a moderately increased and of 6 with a considerably increased platelet turnover. In the low-turnover group the megakaryocyte nuclear lobe number was subnormal cells with basophil cytoplasm were in the majority and the number of megakaryocytes was increased, whereas in the other two groups of megakaryocite population showed a shift to the right, and increased nuclear lobe number, and the number of megakaryocytes, related to the erythroid cells, was increased. It is therefore assumed that in the case of a reduced platelet turnover, the megakaryocytes are damaged, primarily their maturation in the bone marrow. The three groups showed, however, no clinical differences.


Cardiac microstructure in female and male offspring of exercised rat mothers.

The microstructure of the cardiac muscle in eight subgroups of female and male rats was investigated: exercised (EE) and control (EC) offspring of exercised mothers, and exercised (CE) and control (CC) offspring of control, inactive mothers. The differences between subgroups were subjected to variance analysis and multiple-range tests according to Duncan. There were no marked differences in total body weight and weight of the heart related to total body weight. A significant difference (highest values) was shown in the density of muscle fibers and capillaries in the offspring of exercised mothers, which was further potentiated by the additional exercise during postnatal life. Diffusion distance was significantly longer in CC animals; the other subgroups did not differ significantly. There were no significant differences in the reaction of female and male offspring both due to prenatal and postnatal exercise.


Characteristics of optic disc in healthy school children.

The ophthalmoscopic features of the optic discs were studied in a series of 411 non-selected school children representing four age groups from 7 to 15 years. The distribution of the cup disc diameter ratios (C/D) showed that in the majority of the eyes (58.8%) the ratio was 0.2--0.3, independently of the age group. The highest ratio recorded, 0.7, was found in two eyes of the series. An asymmetry of 0.2 or more in the C/D ratios of the eyes was found in 5.2% of the children studied. The correlation between C/D ratio and the age or refraction was not statistically significant although C/D ratio of 0.4 or more was significantly commoner in myopia of -2.0 D. or more than in the other eyes. A preponderance of large C/D ratio was also found in children with a birth weight of 2500 g or less but the difference from the distribution in the total series was not significant. Cilioretinal arteries were detected in 17.7% of the eyes and in 27.3% of the subjects studied. In 8.1% of the children the condition was bilateral. In children with a birth weight of 2500 g or less cilioretinal arteries were found in more than half of the cases.


Do pre- and postchallenge small intestinal biopsies help to diagnose cow's milk protein intolerance?

Twelve infants suspected of cow's milk protein intolerance were challenged with cow's milk after at least one month of cow's milk-free diet. The challenge was clinically positive in seven. Small intestinal biopsies were taken with a multipurpose capsule both pre- and postchallenge (at 24 h) in eight, prechallenge in three, and postchallenge in one. Two or three biopsy specimens were taken at the same time in 15 of the 20 biopsy occasions. The morphology of the mucosa could vary from normal to slight damage at the same biopsy occasion. No difference was found in morphology judged by light microscopy between pre- and postchallenged biopsies. Light microscopy of small intestinal biopsies taken before and at 24 h after milk challenge seems of doubtful value as a routine diagnostic means in cow's milk protein intolerance.


Smoking during pregnancy--hematological observations in the newborn.

Hematological values were measured in 28 newborn infants of mothers smoking 10-20 cigarettes daily during pregnancy, and in 25 infants of non-smokers. Higher hematocrit levels were found on the 1st day of life in infants of smoking mothers (60.8 +/- 5.0%, mean +/- S.D.) compared to controls (57.5 +/- 4.8%) (p less than 0.05). The hematocrit levels correlated positively with the maternal smoking level (r = 0.318, p less than 0.05) and the maternal serum thiocyanate concentrations at delivery (r = 0.389, p less than 0.01). Cord serum values for erythropoietin, serum-iron, transferrin and ferritin showed no statistically significant difference between the two groups. A significant inverse correlation was found between the hematocrit value on the 1st day of life and the cord serum ferritin concentration (r = -0.495, p less than 0.005). The present results suggest that maternal smoking stimulates fetal erythropoiesis, probably through a hypoxic effect on the fetus, dose related to the maternal smoking level. Increased erythropoiesis may cause increased iron incorporation into erythrocytes at expense of iron storage in the bone marrow and reticuloendothelial system.


A comparison of twins for degree of closeness and field dependency.

An examination of Witkin's construct of field dependency was undertaken with a sample of adolescent twin pairs to determine if the degree of closeness in twin relationships would be reflected in the twins' degree of field dependency. Sixteen pairs of monozygotic (MZ) adolescent male twins and the same number of dizygotic (DZ) same-sexed male twins were administered three measures: Nichols and Bilbro's (1966) zygosity questionnaire, Paluszny and Beit Hallahmi's (1974) semantic differential measure of closeness, and Jackson's (1956) short form of the Embedded Figures Test. No significant differences were found between the MZ and DZ twin groups with regard to their expressed closeness to one another, as measured with Paluszny and Beit-Hallahmi's index of closeness; in addition, there were no significant differences between the two twin groups on the measure of field dependency. However, significant relationships of these two variables with intelligence were found and possible reasons for such an occurrence were offered.


The effect of cytochalasin B on chick mesoderm cells as studied by scanning electron microscopy.

The effects of cytochalasin B (CCB) on chick mesoderm cells in vivo was examined by scanning electron microscopy (SEM). The embryos were mounted for New Culture and the mesoderm exposed by dissecting off the endoderm. Cytochalasin B was suspended in saline and the embryos flooded with the suspension. Control embryos were treated with saline alone. The embryos were reincubated for varying times at 37 degrees C. In the treated embryos the mesoderm cells were rounded and separated from each other. Many had long branched processes and rough surfaces. These changes became more pronounced as treatment time was increased. They were also reversible on reincubating treated embryos in the absence of cytochalasin B. The morphological changes produced by CCB are thought to be due to an effect on the cytoskeleton, either a direct disruptive effect or detachment of skeletal microfilaments from the cell membrane. There may also be a direct removal of cell surface materials leading to the observed surface roughening of treated cells.


Mastitis-metritis-agalactia complex in sows: effect of the dosage of oxytocin on intramammary pressure in lactating healthy sows.

The dose-response and time-response relationships between injected oxytocin and intramammary pressure were investigated in normal lactating sows. In less than 39 s after 20, 40, or 80 U of oxytocin was given (IM injection), there was a rapid initial increase in intramammary pressure (15 to 27 mm of Hg) which lasted 22 to 32 s. After this initial response, there were secondary oscillations in pressure which lasted approximately 40 minutes (20 U) and up to 60 minutes (40 or 80 U). Changes in intramammary pressure during each oscillation varied between 1 and 5 mm of Hg. Mean values for frequency and amplitude of oscillations and total work (area under the trace) were measured. Compared with response obtained after 20 U of oxytocin was given, responses obtained at the 40-U or 80-U dose level had an increased frequency (150.0% and 249.0%, respectively) and total work (36.6% and 104.4%, respectively), but not amplitude. Thus, there may be some clinical advantage in milk let-down effect when sows are given the larger doses of oxytocin (40 or 80 U). These results indicate that newborn pigs should be allowed to nurse at the same time in which oxytocin is injected.


Porcine mastitis-metritis-agalactia (MMA) syndrome: mammary gland responsiveness to oxytocin given to healthy sows during lactation.

Mammary gland responsiveness to exogenous oxytocin during lactation was assessed by measuring changes in intramammary pressure of healthy sows given (IM injection) synthetic oxytocin (40 U). Response to oxytocin was measured once a week for the first 8 weeks of lactation. Recordings of pressure changes were expressed as mean area (cm2) under the trace at each 10-minute interval over 30 minutes after oxytocin had been given. During the 2nd week of lactation, there was a 55.3% increase (P less than 0.05) in responsiveness to oxytocin (25.1 +/- 4.2 cm2/10 minutes) as compared with the 1st week (13.9 +/- 2.2 cm2/10 minutes). Responsiveness decreased, however, from the 2nd to the 8th week. Since the incidence of mastitis-metritis-agalactia in sows is particularly high during the 1st week of lactation, low responsiveness of the mammary gland to oxytocin may be a contributing factor.


Transplacental transmission and neonatal infection with swine influenza virus (Hsw1N1) in swine.

To study the question of chronicity or latency of swine influenza virus (Hsw1N1) infections in swine, newborn pigs were exposed to the virus in two experiments, and pregnant gilts were exposed in another experiment. Of five pigs exposed at 5 days of age, virus was isolated from throat swab samples of all (up to 10 postexposure days (PED) in one pig) and from a blood sample from one pig on PED 1 and 3. Virus was not isolated from urine, tissues, or explants of organs from pigs euthanatized PED 20 to 67, and disease was not evident. Of 11 pigs exposed within 2 hours of birth (before consuming colostrum), virus was shed for longer periods (for 10 and 11 days in four pigs) and severe respiratory tract pathologic changes developed. However, there was no evidence of chronic or latent infections. There was evidence of transplacental transmission of virus in one of ten pigs born to pregnant gilts that were exposed 10, 24, and 39 days before parturition, respectively.


Pharmacokinetic evaluation and mammary excretion of tamethicillin in the healthy goat.

We evaluated the pharmacokinetics and the mammary excretion of a new beta-lactam antibiotic derivative, the diethylaminoethyl ester of methicillin, commonly known as tamethicillin. Tamethicillin is a hydrolyzable weak basic ester (pro-drug) that is converted to methicillin in the body. Its pharmacokinetic profile compares favorably with that of methicillin. In this sense, tamethicillin had five times greater distribution volume than methicillin, and both its slow phase half-time (t 1/2) and elimination half-time (t 1/2 Kel) were clearly greater. In addition, our experimental studies on mammary excretion in the goat have demonstrated a better selectivity for the udder of tamethicillin as compared with methicillin. Results of 2 years of field experience show that tamethicillin can be considered a useful alternative for the treatment of mastitis in livestock, especially in mastitis due to beta-lactamase-producing Staphylococcus.


Unusual XX/XY chimerism.

Apparently identical twin boys are both XX/XY and have two populations, A1 and B, of cells in their peripheral blood. Chimerism in somatic tissue outside the blood cells can be demonstrated in only one of the twins. From analysis of chromosomes and many gene markers the mechanism of origin of the unusual twins remains unclear.


Permanent tooth sizes in 46,XX-males.

Measurements of permanent tooth sizes in four XX-males showed their teeth to be smaller than those of male controls and similar in size to those of female controls. The teeth of the XX-males were smaller than those of their first-degree male relatives and of the same size as those of three of their mothers. The teeth of three fathers of XX-males were similar in size to control males and the teeth of three mothers of XX-males were similar in size to control females. The detailed knowledge that exists regarding the sequence and timing of tooth crown development allows the following implications to be made from our results. Growth retardation in XX-males is of primary genetic origin and is due to the absence of the gene(s) normally located on the Y-chromosome. Growth retardation, compared to normal males, is apparent and final three years after birth, conceivably begins after 2--3 months of foetal life and persists during childhood. It is unlikely that XX-males have had a Y-chromosome at any stage. If maleness is caused by a recessively inherited translocation or a mutational acquisition of the testis-determining gene(s), the genes influencing growth are not involved in either mechanism.


Alexia, without agraphia, due to brain tumor: a reversible syndrome.

Alexia without agraphia occurred in a 41-year-old man suffering from a left occipital brain tumor. The syndrome disappeared following excision of the neoplasm.


Is it necessary to warm infants' feeds?

The effect of temperature on gastric emptying after milk feeds was studied in 31 newborn infants. Test meals were a commercially prepared modified cows' milk (a) at body temperature and (b) at room temperature. Our results suggest that temperature has no effect on gastric emptying.


[Ultrastructural changes induced by a brief period of anoxia in cerebral cortex tissue culture].

Explants of long-term cultures of nervous tissue of the rat cerebral cortex were placed for 30 min in a pure nitrogen atmosphere and then for 3--5 days transferred to the conventional cultivation co conditions. Electron microscope examinations showed that most severe changes occurred in the elements of oligodendroglia in the cytoplasm of which numerous lysosomes, large vacuoles, deposits of glycogen accumulated and myelin figures were formed. The damage of these cells appears to result in the degeneration of myelin sheaths. Edematous changes and glycogen accumulation were prevalent in astrocytes. Alongside with this, neurons had no such severe changes under these treatments. Its is emphasized that the intensity of reproducible oxygen deficiency must be taken into consideration in the evaluation of the sensitivity to anoxia of various nervous tissue elements.


Further study on the effect of norethisterone enanthate, an injectable contraceptive on body functions.

One hundred and fortythree healthy Bengali women have received norethisterone enanthate, as injectable contraceptive in doses of 200 mg. intramuscularly at intervals of 10 to 12 weeks. The drug have been found to be almost 100 percent effective in the control of fertility. Menstrual disturbance, e.g. amenorrhoea, irregular bleeding and spotting, appeared to be the main complaints of the clients during the initial period of the therapy; but these did not persist long. There was no ill effect of the drug on lactation. No significant change in body weight, blood pressure, platelet count, fasting blood sugar, serum cholesterol and total plasma protein level was observed following administration of norethisterone enanthate over one year.


Incorporation of 3H from delta-(L-alpha-amino (4,5-3H)adipyl)-L-cysteinyl-D-(4,4-3H)valine into isopenicillin N.

1. delta-(L-alpha-Amino[4,5-3H]adipyl)-L-cysteinyl-D-[4,4-3H]valine has been synthesized from its constituent amino acids, the L-alpha-amino[4,5-3H]adipic acid being obtained by reduction with 3H2 of methyl 5-acetamido-5,5-diethoxycarbonylpent-2-enoate and subsequent decarboxylation and hydrolysis. 2. In a cell-free system prepared by lysis of protoplasts of Cephalosporium acremonium 3H was incorporated from the doubly labelled tripeptide into a compound that behaved like penicillin N or isopenicillin N. The relative specific radioactivities of the alpha-aminoadipyl and penicillamine moieties of the penicillin were the same (within experimental error) as those of the alpha-aminoadipic acid and valine residues respectively of the tripeptide. 3. The behaviour of the labelled alpha-aminoadipic acid from the penicillin to the L-amino acid oxidase of Crotalus adamanteus venom showed that it was mainly L-alpha-aminoadipic acid. 4. The results are consistent with the hypothesis that the carbon skeleton of the LLD-tripeptide is incorporated intact into the penicillin molecule and that the first product is isopenicillin N.


Characterization of subcellular components in synchronized hepatoma cells as a function of the cell cycle.

The specific activity and subcellular distribution of marker enzymes for the main subcellular components were analysed in homogenates of synchronized hepatoma cells (Morris 7288c), obtained by selective detachment at mitosis combined with a metaphase block with Colcemid. Markers for lysosomes, mitochondrial outer membrane, plasma membrane and cytosol are synthesized throughout the cycle at the same rate as the bulk of cellular protein. Larger variations are observed for a Golgi marker; after a decrease around mitosis, the specific activity of galactosyltransferase increases steadily from middle G(1)-phase on, and at the end of G(2)-phase it is nearly twice that observed at the beginning of G(1)-phase. Our results show that synthesis of cytochrome oxidase may occur preferentially in G(2)-phase. Large modifications of the density distribution of lysosomes are observed during the cell cycle; the median equilibrium density of lysosomal markers decreases in G(1)-phase, and some increase in soluble activity occurs at the same time. Reverse changes occur progressively during S- and G(2)-phases. At mitosis, Golgi galactosyltransferase shows a more dispersed distribution, and modifications in the density distribution of endoplasmic-reticulum NADPH-cytochrome c reductase are observed. The latter can be most easily explained by a detachment of ribosomes from endoplasmic-reticulum membranes. No significant modifications occur in mitochondrial and plasma-membrane markers.


Cell-free conversion of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine into an antibiotic with the properties of isopenicillin N in Cephalosporium acremonium.

Cell-free extracts of antibiotic-negative mutants of Cephalosporium acremonium converted delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (LLD-tripeptide) into an antibiotic that was destroyed by penicillinase. The enzymic activity of the extracts was destroyed by boiling, but was not inhibited by cycloheximide. LLL-Tripeptide was totally inactive as substrate. The product resembled isopenicillin N, but not penicillin N, in its antibacterial spectrum. We propose that isopenicillin N is the first product of cyclization of LLD-tripeptide.


Effect of human, bovine and ovine prolactin on DNA synthesis by organ cultures of benign human breast tumours.

Ten benign breast tumours from 9 female patients (8 with fibrocystic disease and 1 with fibroadenoma) and 1 male patient (with gynaecomastia) were processed into slices and individually cultured for 2 days in serum-free Medium 199. [3H]-TdR was added to the culture medium to assess DNA synthesis. The addition of human prolactin to the culture medium (500 ng/ml) significantly (0.05 greater than P greater than 0.01) increased DNA synthesis; all 9 biopsy specimens from the 9 female patients responded positively to this hormone. Ovine prolactin (500 ng/ml) and bovine prolactin (500 ng/ml) increased the mean incorporation of [3H]-TdR into extracted DNA and increased the mean number of [3H]-TdR-labelled cells, but this increase did not reach the 5% level of probability. The sole case of male breast dysplasia analysed in this study did not respond to either human, ovine or bovine prolactin. These results provide evidence that human prolactin and, to a lesser degree, ovine and bovine prolactin are direct mitogenic stimulants to the epithelium in human (female) benign breast tumours.


Vitamin A, zinc and lung cancer.

Serum vitamin A concentration were measured in 26 newly diagnosed lung-cancer patients and found to be significantly lower than those of patients of similar age with either non-malignant lung or non-lung diseases. The levels of vitamin A in the lung-cancer patients, but not in the controls, were significantly correlated with serum concentrations of retinol-binding protein (RBP) and zinc. It is suggested that low levels of zinc might reduce the synthesis of RBP and thus reduce the mobilization of vitamin A from the liver.


The outcome of pregnancy after cone biopsy of the cervix: a case-control study.

We investigated the outcome of pregnancy after cone biopsy of the cervix. We found that preterm delivery and low birth weight were commoner and the mean duration of labour longer in women who had a cone biopsy than amongst matched controls. Rapid labour (under two hours) was not significantly more common after cone biopsy.


Diurnal variations of zinc, copper and magnesium in the serum of normal fasting adults.

Serum levels of copper, magnesium and zinc exhibit circadian rhythms in physiologically normal subjects eating normally. The same study was repeated with fasting subjects in order to determine the effect of daily food intake on these fluctuations. Blood samples were taken at 3 hour intervals, from 6 h to 18 h. Copper and magnesium no longer exhibit circadian rhythms in fasting subjects. In the case of zinc, however, a particularly interesting rhythm is observed, with a drop at 9 h and 15 h and an abrupt increase at 18 h.


Identification of 5-hydroxyhexanoic acid in the urine of twin siblings with a Reye's-like syndrome associated with dicarboxylic aciduria and hypoglycaemia and with similarities to Jamaican vomiting sickness.

Twin male infant siblings who presented in Harrow, UK, with a Reye's-like syndrome associated with profound hypoglycaemia, vomiting, diarrhoea, coma and death in one child, with dicarboxylic aciduria, and similarities to Jamacian vomiting sickness (hypoglycin toxicity) have been shown to excrete large amounts of a previously unrecorded urinary organic acid. This has been identified as 5-hydroxyhexanoic acid by gas chromatography mass spectrometry using a synthesized standard. Concentrations observed were 340 and 330 mg g-1 creatinine in the two patients. The metabolic precursor of the urinary acid is suggested to be hex-4-enoic acid, a probable chemical toxin closely related to the active organic acid metabolite of hypoglycin. The possibility of omega - 1 oxidation of hexanoic acid to 5-hydroxyhexanoic acid in these and other patients with dicarbocylic aciduris is also discussed.


[Carcinoma in situ of the uterine cervix: treatment (author's transl)].

Persisting dysplasias are nothing but carcinomas in situ with special differentiation. As such they become directly invasive and are differently located as classical carcinomas in situ. Intraepithelial lesions arise in clearly defined fields and do not spread into neighbouring epithelia. Most lesions are located within the cervical mucosa and less frequent in the region of original squamous epithelium. Treatment must be based on the knowledge of changes being truly intraepithelial and upon their extent. When primarily extirpating the uterus such knowledge is not available. Of 160 cases of primary hysterectomy two patients died of cancer. Vaginal hysterectomy produced better results than the abdominal. Electrocoagulation, cryosurgery and laser treatment destroy lesions without exact knowledge of their extent. Conisation combined with careful sectioning of specimen gives the best survey of the lesions. Of 1 219 conisation cases conisation was the only therapy in 918 patients. None of these died of cancer.


The cerebral malformation of the amnionic band syndrome.

The Amnionic Band Syndrome is a not uncommon disorder of the fetus which may result in cerebral malformations that mimic anencephaly. It is important to distinguish these two entities because of differences in pathogenesis and risk of recurrence. A preliminary stillborn female of 29 weeks gestation with multiple anomalies, including cerebral-placental fusion, cranial agenesis, cleft lip, syndactyly and ectopic liver is presented. These malformations are typical of the Amnionic Band Syndrome, an entity which has not been described in the neurologic literature.


Cis-dichlorodiammineplatinum(II) in advanced soft tissue and bony sarcomas: a Southwest Oncology Group Study.

cis-Dichlorodiammineplatinum(II) (DDP), at a dose of 15 mg/m2/day x 5 consecutive days, was administered to 68 evaluable patients with metastatic soft tissue and bony sarcomas. All patients, except one, had received extensive prior chemotherapy and had had progressive disease at the start of the study. Responses observed included one complete response in a patient with mesothelioma and three partial responses in patients with soft tissue sarcomas (7%). No responses were seen in 18 patients with bony sarcomas. Significant leukopenia and thrombocytopenia were observed in less than 20% of evaluable courses, although two patients manifested life-threatening leukopenia (less than 1000 cells/microliter) and three had life-threatening thrombocytopenia (less than 24,000 cells/microliter). Nephrotoxicity was noted in less than 25% of evaluable courses. Nausea and/or vomiting was recorded in 55% of evaluable courses. DDP is considered to be marginally active in the secondary treatment of metastatic sarcomas at this dose and schedule. Further studies of DDP in mesothelioma are indicated.


Serum IgE levels in rats infected with Dipetalonema viteae L3 larvae.

Serum IgE levels were measured by radioimmunoassay in rats infected with various doses of L3 infective stage larvae of Dipetalonema viteae. A high stimulation in total serum IgE levels was found with minute doses as well as with large doses of parasite, and IgE levels remained elevated for several months. No further increase in IgE levels was induced by a secondary infection.


Electron microscope study of 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid, an exfoliative antispermatogenic agent, in the rat testis.

We were interested in discovering whether the antifertility agent, DICA [1-(2,4-dichlorobenzyl)-1-H-indazole-3-carboxylic acid] induced Sertoli cell tight junction damage. Testis were fixed in 1% lanthanum nitrite cacodylate-buffered 2% gluteraldehyde at various times following a single oral 100 mg/kg dose of DICA. In control animals adluminal lanthanum was never seen. At one and ten days following DICA treatment adluminal lanthanum was seen. This suggests that the Sertoli cell tight junctions are more permeable to lanthanum following DICA treatment.


Some aspects of the changes induced by chronic barbital treatments in the male rat.

Oral barbital treatments consisting of average daily doses of 200 mg/kg with durations of 15-50 weeks have been used to induce functional tolerance and physical dependence. Tolerance is usually studied with a hexobarbital threshold while increased excitation has been studied by various means, such as induction of convulsions with pilocarpine or choline. After barbital treatments for 30 weeks brain weights are reduced by approximately 10 per cent. This reduction is not due to changes in body weight or water content of the brain. The decrease is still found 30 days after the end of the barbital treatment. Supersensitivity to pilocarpine and reduced acetylcholine content in the brain are some earlier published indications that cholinergic mechanisms are involved in abstinence. Further studies have shown that atropine (8 mg/kg given intraperitoneally on the third day of abstinence) can reduce the tolerance to hexobarbital. An atropine treatment (4 mg/kg per day for 2 weeks) given late in the period of abstinence following a barbital treatment can induce a tolerance to hexobarbital. A prerequisite for this tolerance is the earlier barbital treatment. A steric selectivity in the action of hexobarbital is indicated by the interaction between atropine (8 mg/kg) and the isomers of hexobarbital. In normal rats only the potent isomer of hexobarbital is influenced by atropine. If the convulsive effect of choline is utilized in a threshold test, an increased sensitivity indicating increased excitation is found on day 10-11 of the period of abstinence when other signs of excitation are returning to normal. When these signs are maximal, on day 3, no increased sensitivity to choline is found. Choline seems to act on a selective mechanism which is revealed only late in the abstinence period. Hexobarbital thresholds performed on two phases of the blood ethanol concentration curve were used to study the interaction between ethanol and hexobarbital during abstinence following a barbital treatment. Immediately after the end of the barbital treatment, a general tolerance was present. A week later, ethanol eliminated the tolerance to hexobarbital. On day 15 of abstinence, no tolerance to hexobarbital was found, but there was a tolerance to ethanol on the increasing portion of the blood ethanol concentration curve. Thus, it is unlikely that physical dependence and functional tolerance constitute a single phenomenon in abstinence after barbital treatments. Cholinergic mechanisms seem to be involved in the presumably adaptive changes that can be recorded.


Behavioral rating scales for assessing phencyclidine-induced locomotor activity, stereotyped behavior and ataxia in rats.

Behavioral rating scales were developed for quantification of phencyclidine (PCP)-induced locomotor activity, stereotyped behavior and ataxia in rats. The dose-response relationship for PCP-induced locomotor activity was found to be an inverted U-shaped function over the first 25 min after injection while over the last 30 min of the experiment the function was highly linear. A linear dose-response relationship was found for ratings of stereotyped behavior and ataxia throughout the 90 min period of observation. The ratings of these two behaviors were found to be closely parallel. The effects of PCP on locomotor activity were found to be greatest during those intervals when stereotyped behavior and ataxia were at moderate levels. Ratings of locomotor activity may be confounded by ataxia when PCP is administered alone or in combination with other drugs.


Neurochemical aspects in pathogenesis of alcohol and drug dependence.

At present, catecholamines are considered to play a significant role in the regulation of psychic function and emotional states. Our investigations have revealed significant changes in peripheral catecholamine metabolism in alcoholic patients. Catecholamine metabolism in the brain and in the periphery are rather autonomous, and thus in our studies we compared the effects of alcohol on dopaminergic and noradrenergic systems in different brain regions as well as in the periphery. We found a significant decrease in noradrenaline levels in different regions of the CNS, particularly midbrain, hypothalamus and hippocampus. In chronic studies with rats, catecholamine metabolism was studied in animals chronically treated with alcohol, those treated with a single dose after chronic treatment, and those animals undergoing withdrawal from alcohol. Neuropharmacological and neurochemical studies were accompanied by electrophysiological monitoring of the effects of alcohol.


Non-specificity of "behavioral despair" as an animal model of depression.

When mice are forced to swim in a restricted space, they will cease attempts to escape and adopt a characteristic immobile posture which can be readily identified and timed. Imipramine decreased the duration of immobility in a 4 min swimming test in a dose-related manner. Likewise, caffeine, triiodothyronine and pentobarbital reduced immobility. These latter findings shed doubt upon the specificity of the behavioral despair swimming test to identify substances with antidepressant activity.


Enkephalin levels decrease in rat striatum during morphine abstinence.

Male Sprague-Dawley rats were treated with morphine for 11 days. Saline-injected animals served as controls. The striatal enkephalin levels were measured with a radioimmunoassay 2, 24 and 48 h after withdrawal. There was no change 2 h after the last morphine injection, but a marked reduction after 24 h and a slight decrease after 48 h. No decrease in enkephalin levels was found 12 and 24 h after a single dose of 20 mg/kg morphine.


Selection criteria for family therapy.

The patient selection criteria for most modalities of psychotherapy have not yet been clearly articulated. This paper presents a decision-tree model outlining the factors that incline a clinician to perform a family evaluation, then to decide upon family treatment instead of another form of therapy, and finally to settle upon the particular duration and intensity of family treatment. We have compiled screening criteria, based on research and clinical opinion, to be applied in the utilization review of the decisions made at each of these steps. This method can be used to evaluate the appropriateness of care and render decision-making explicit and accountable; it may also have considerable value in training and research.


Effect of coprophagy on bile acid metabolism in the rabbit.

The effect of coprophagy on the 7 alpha-dehydroxylation of biliary bile acids was studied in the rabbit. Bile acid composition of bile and intestinal contents was analyzed by gas-liquid chromatography and thin layer chromatography. Biliary bile acid composition of normal rabbits (n = 5) was: deoxycholic acid, 95.3 +/- 1.0SE % and cholic acid, 2.3 +/- 1.1SE %. When coprophagy was prevented, significant alterations were observed in biliary bile acid composition, including a considerable decrease in deoxycholic acid (82.5 +/- 2.8SE %, p less than 0.01) and a marked increase in cholic acid (15.2 +/- 3.0SE %, p less than 0.002). These results indicate that coprophagy is a factor causing an increase of the 7 alpha-dehydroxylated bile acid, deoxycholic acid (and lithocholic acid when the animals were fed chenodeoxycholic acid) in rabbit bile.


Penetration of ovicidal fungi into altered eggs of Ascaris lumbricoides.

Eggs of Ascaris lumbricoides exposed to temperatures of 40--60 degrees C for 1 hour or irradiated by high doses of UV light are more massively attacked by ovicidal fungi than the intact eggs. The authors assume that the more rapid and increased effect of ovicidal fungi in the soils of the tropics and subtropics is due to greater insolation of the surface layers and their higher temperature.


Dicentric Y-chromosome mosaicism in a girl with clitoral hypertrophy.

A 12-year-old girl with small stature and a hypertrophic clitoris was found to be mosaic for 45,X/46,X.dic(Y)(qtertop11:p11toqter)/46,XX/47,XX,dic(Y)(qtertop11:p11toqter). The dicentric chromosome was identified using Q-banding. These findings indicate mitotic instability of the dicentric Y, as well as the presence of an X chromosome in this patient.


Experimental infection of rabbit ligated ileal loops with Treponema hyodysenteriae.

An in vivo animal model was used to assess the enteropathogenicity of the etiological agent (Treponema hyodysenteriae) of swine dysentery. Multiple ligated ileal loops, prepared in New Zealand white rabbits, were challenged with either pathogenic (B78 and B204) or nonpathogenic (Pu) isolates of the organism. The pathogenic isolates induced the onset of intestinal fluid accumulation as early as 4 h, with maximal fluid induction at 18 h postchallenge. Gross lesions of the intestinal mucosa, observed in ileal loops of rabbits sacrificed 24 h postchallenge, were characteristic of swine dysentery. Both pathogenic isolates colonized the epithelial surface and eroded the mucosal barrier, as determined by histological and scanning electron microscopic observations. Intestinal fluid accumulation and erosion of the mucosal barrier were not observed in ileal loops exposed to the nonpathogenic isolate (Pu) or to either of the nonviable pathogenic (B78 and B204) isolates. The ability of pathogenic isolates to initiate and produce infection in rabbit ligated ileal loops, which closely resembles the disease in swine, provides a system with which to study experimental swine dysentery.


Breast cancer in black American women.

A case-control study of breast cancer among Black American women was conducted in seven hospitals in New York City from 1969 to 1975. Results are reported for 127 cases and 317 controls. Compared to women with a first birth before age 19, those with a first birth after 25 had a relative incidence rate for breast cancer of 3.8 and 2.2 for the pre- and postmenopausal age-groups, respectively. Compared to nulliparous women, parous women had a relative incidence rate of 0.6 for premenopausal and 0.7 for postmenopausal women. The incidence rate of breast cancer for women with a menopause after age 49 was estimated to be 3.1 times that of women with a menopause before age 45. Thus, the known risk factors for breast cancer among Whites are also related to the etiology of the disease among Blacks. The incidence rate of breast cancer has increased among younger Blacks since 1947 and is now similar to that among younger Whites. However, among older women, the incidence rate is still appreciably higher for Whites. The most likely explanation of this pattern is that Black women born since about 1925 are being exposed at the same frequency as White women to the causes of breast cancer.


The L1210 assay for immune complexes: application in cancer patients and correlation with disease progress.

Immune complexes (ICs) were determined by the non-complement-dependent L1210 radioimmune assay on 132 serum samples collected from 53 patients with a variety of cancers. Both the mean IC levels and frequency of positive tests were significantly greater in cancer patients (mean = 96 +/- 100 microgram/ml, 46% positive) than in a control group of 67 normal healthy blood donors (mean = 39 +/- 15, 3% positive). When cancer patients were assorted into groups by disease progress, those with large or progressing tumors had significantly higher mean values (136 +/- 129) and frequency of positives (75%) than those with small or regressing tumors (58 +/- 18, 22% positive). In lung cancer patients, IC levels showed a strong inverse correlation (rs = -0.903) with survival time in patients who died, and appeared to be a better prognostic indicator than performance status (Karnofsky scale) at time of diagnosis. Serial IC measurements taken on several patients showed a decrease in levels concomitant with a favorable response to cytoreductive therapy, sustained normal levels during periods of prolonged remission, and a rise to elevated levels with (and sometimes preceding) documentation of new metastases.


Gustatory preferences during estrus cycle in rats.

Estrus cycle has been used as a base to study gustatory responses in rats under conditions of two-bottle choice test given for one hour daily, and the data pooled respectively for diestrus/metestrus (D/M) and proestrus/estrus (P/E). Glucose (13.5%), sodium saccharin (0.2%), sodium chloride (0.9%), citric acid (0.004%) and quinine sulphate (0.002%) was each paired with water and a particular solution was presented daily for one week. Two days gap was given between two different solutions when only water was made available in both the bottles. An increased preference for glucose and saccharin, decrease to sodium chloride and no change in citric acid and quinine sulphate was observed at P/E. The differential gustatory response is perhaps linked to the levels of ovarian and hypophyseal hormones at the time of ovulation.