Primary structure of the nucleic acid from the 1,4-alpha-glucan branching enzyme.

The primary structure of the nucleic acid from the branching enzyme 1,4-alpha-D-glucan: 1,4-alpha-D-glucan 6-alpha-(1,4-alpha-glucano)-transferase (2.5-S RNA) isolated from rabbit muscles has been elucidated. The polyribonucleotide consists of 31 nucleotides; the unique features of the polyribonucleotide are the unusually high content of modified nucleotides (32%) and guanine residues (40%). Apparently 2.5-S RNA belongs to a class of nucleic acids unknown up to now. It is the first time that the structure of a nucleic acid component from a ribonucleoenzyme has been defined. This work is a preprequisite for gaining insight into the intimate activating effect of the poly-ribonucleotide on the enzyme action.


Alterations in the processing of rat-liver ribosomal RNA caused by cycloheximide inhibition of protein synthesis.

Cycloheximide given in vivo at low doses (2--5 mg/kg body weight) causes within 30 min a complete inhibition of protein synthesis in rat liver. The labelling of nuclear proteint is also strongly inhibited. Under these conditions, the amount of nucleolar 45-S pre-rRNA and its [14C]-orotate labelling remain unaffected for at least 4 h. These results show that initially the rates of synthesis and processing of 45-S pre-rRNA are not appreciably altered. On the other hand, drastic alterations in the 45-S pre-rRNA processing pathways occur at the early stages of cycloheximide action. Formation of 18-S rRNA is abolished and that of 28S rRNA is reduced to about half the level in control rats. This dichotomy in the production of the two ribosomal particles may be correlated with a block in the formation of 41-S and 21-S pre-rRNA. Generation of 36-S and 32-S pre-rRNA is still taking place, but the rate of their processing to nucleolar 28-S rRNA is decreased, thus causing the accumulation of these two pre-rRNA species. In parallel, processing of 45-S pre-rRNA to an aberrant 39-S rRNA species is markedly enhanced. The results obtained show that the channelling of nucleolar pre-rRNA along alternative processing pathways is under stringent control by the continuous supply of critical protein(s).


Fluorescence depolarization studies and phase transition in human apoprotein . phospholipid complexes.

The microviscosity of unilamellar vesicles of dimyristoyl-3-sn-phosphatidylcholine and that of phosphatidylcholine . apoprotein complexes was followed by fluorescence depolarization after labeling with 1,6-diphenyl-1,3,5-hexatriene. The transition temperature from gel-crystalline to liquid-crystalline phase in 24 degrees C for the dimyristoyl-phosphatidylcholine vesicles and is shifted to around 30 degrees C in the complexes between phosphatidylcholine and apoA-I, apoA-II, apoC-I, apoC-III proteins while the cooperativity of the transition is decreased. At temperatures below the transition of the phospholipid, the microviscosity of the complexes of phosphatidylcholine with apoA-I, apoA-II and apoC-I proteins is lower than that of the phosphatidylcholine, while the opposite effect is observed above 30 degrees C. The phosphatidylcholine . apoprotein complexes isolated on a Sepharose 6B column have a molecular weight around 100 000 and a phosphatidylcholine/apoprotein ratio of 2--2.6 (w/w). The microviscosity measurments at 35 degrees C performed after elution of the column enable the complex to be detected. The size and microviscosity of the apoprotein . phosphatidylcholine complex is compatible with a model where the vesicular structure has disappeared and the amino acid side chains present hydrophobic interaction with the phosphatidylcholine acyl chains.


Identification of mRNA in the slime mold Physarum polycephalum.

Using a differential extraction procedure which had previously been shown to yield one nucleic acid fraction enriched in cytoplasmic RNA and another enriched in nuclear RNA, we have been able to isolate two polyadenylated RNA populations from microplasmodia of Physarum polycephalum. The poly(A)-containing RNA from the cytoplasmic-enriched fraction accounts for approximately 1.2% of the cytoplasmic nucleic acid, has a number-average nucleotide size of 1339+/- 39 nucleotides, and has been shown, in a protein-synthesizing system in vitro, to be capable of directing the synthesis of peptides which have also been shown to be synthesized in vivo by microplasmodia. The poly(A)-containing RNA from the nuclear-enriched fraction has a number-average nucleotide size of 1533 +/- 104 nucleotides and represents a mixture of cytoplasmic and nuclear adenylated RNA molecules. Based upon these observations, we have identified the polyadenylated RNA isolated from the fraction enriched in cytoplasmic nuclei acid as Physarum poly(A)-containing messenger RNA.


Anomalous systemic arterial supply to the basal segments of the lung presenting with a murmur.

A murmur was discovered on routine preschool physical examination of a 5 year and 7 month-old boy. A lower lobe lesion was detected by chest X-ray. Aortography demonstrated that a large systemic artery from the descending thoracic aorta supplied the basilar segments of the left lower lobe, which had no normal pulmonary arterial supply. A clinical diagnosis of intralobar sequestration of the lung was made, and left lower lobectomy was performed.


Clinical and biochemical study of a child with the non-neuronopathic-Type B form of Niemann-Pick disease.

A child with Niemann-Pick disease type B, diagnosed at the age of two years and followed up for three years is described. Despite extensive visceral involvement--as deduced from marked hepatosplenomegaly and pulmonary infiltration--the child is in general good health and has no apparent neurologic abnormality. Biochemical studies revealed a tenfold increase of sphingomyelin content in his liver biopsy specimen and a markedly reduced sphingomyelinase activity in peripheral blood leukocytes. His parents were found to be heterozygous carriers of the disease, showing sphingomyelinase activity values intermediate between those of patient and healthy subjects. The relevant literature, concerning patients with the non-neuronopathic type B form, is reviewed.


A girl with an end-to-end fusion of two X'S.

An abnormal large chromosome was seen in the karyotype of a 3-year-old girl with features of Turner's syndrome: i.e., short stature, cubitus valgus, coarctation of aorta. With the banding technics this abnormal chromosome appears to be the result of a fusion of two X chromosomes, short arm-to-short arm. This chromosome has two regions with C-heterochromatin and is late replicating.


Complicated optic atrophy (Bher's disease) associated with epilepsy and amino acid imbalance.

A case of Behr's disease (complicated optic atrophy) associated with epilepsy and with imbalance of the free amino acid pool in plasma and cerebrospinal fluid, quite similar to that identified in patients with hereditary ataxias, is reported. The latter finding stands for a closer correlation between the two clinical entities.


Transient hyperkinesia after a single intravenous perfusion of diphenylhydantoin. Report of a case associated with nontoxic plasma levels of diphenylhydantoin.

Transient hyperkinesia was observed in a 16-year-old epileptic and mentally retarded patient after a single intravenous perfusion of diphenylhydantoin (DPH). No clinical signs of DPH intoxication were associated with the movement disorder. Repeated plasma anticonvulsant level determinations never showed toxic concentrations of DPH. Since a few spontaneous episodes of hyperkinesia had been observed before, the DPH intravenous perfusion could have unmasked a preexisting latent movement disorder in our patient. However, neuroradiological investigations failed to demonstrate the existence of any anatomical damage of the basal ganglia, and HVA as well as 5-HIAA levels measured in the CSF with the probenecid technique were within the normal range 2 months after cessation of hyperkinesia. HVA and 5-HIAA levels have also been measured in the CSF during the period with hyperkinesia; the results are discussed with reference to previously published data concerning cerebral monoamine metabolism in drug-treated epileptic patients.


Possible interference between migrainous and epileptic mechanisms in intercalated attacks. Case report.

The possibility that epileptic seizures and classic migraine episodes may occur in the same patient is discussed. The probable relationship between the neurophysiological mechanisms which underlie both types of attacks has not yet been agreed upon. The case of a young man who suffered from classic migraine and who presented two convulsive epileptic attacks, preceded by visual aura is described. The EEG showed an epileptogenic occipito-temporal focus which corresponded to the region of the scotoma origin. A possible connection between scotoma in migraine and epileptic discharge is discussed. It is proposed that spreading depression, as the basis of the migraine prodomata, was preceded by a moment of intense neuronal excitation which changed the epileptic intercritical activity into a critical one.


Variation of immunoglobulin G and total protein concentrations during lumbar cerebrospinal fluid collection.

In successive lumbar samples of cerebrospinal fluid (CSF), each consisting of 5 ml, immunoglobulin G (IgG) and total protein were determined. Variation was studied by comparing the values in the initial sample with values in succeeding samples. In 13 out of 17 patients, IgG was reduced in sample 2. There was no reduction in the following samples. The concentration of IgG in sample 2 was below 50% of the concentration in sample 1 in 2 patients and below 70% in 9 patients. IgG was also reduced if the concentration in each sample was given as percent of the total protein concentration. The total protein concentration was not significantly reduced during collection of 25 ml of CSF. IgG was increased in sample 2 in 3 out of the 4 patients with neurological diseases since childhood. In 1 patient there was a considerable rise in the total protein concentration after collection of the first 5 ml, without a corresponding rise of IgG concentration. In clinical practice, the portion to which the CSF sample belongs should be noted, and comparison of values from various patients should be made between equivalent samples.


Detection and genetic counselling of subclinical and carrier states in Duchenne muscular dystrophy.

23 potential carriers of Duchenne muscular dystrophy (DMD) and 20 of their apparently healthy brothers were studied for evidence of any subclinical form of the disease. The results of the study confirmed that it was possible to confirm the diagnosis of a 'high genetic risk' carrier by integrating the results of clinical studies, estimation of basal serum CPK, steroid-CPK test, EMG and ECG observations. Similarly, the subclinical state of DMD could also be detected with certainty in 10% of the brothers of DMD carriers. The results may be applied for genetic counselling to bring down the incidence of the disease in the community.


Two cases of choreatic syndrome caused by polycythemia vera.

Two patients with choreatic syndromes caused by polycythemia vera recovered after treatment of the polycythemia by only two venesections: this proves that the syndrome is due to reversible alterations. Investigations of the cerebral circulation in one of the patients showed that blood flow was lowest in the grey matter at the basal region of the brain: this suggests that the alterations might mainly occur there. However, investigation of erythrocyte rheology, glucose-6-phosphate dehydrogenase, serum concentrations of caeruloplasmin and serotonin, and urinary excretion of epinephrine, norepinephrine and vanillylmandelic acid gave normal results in both patients. There are therefore no indications as to the possible pathophysiology of these alterations. There are now 24 cases reported, including our 2 patients, which suggests that the association of these two diseases may not be so rare as supposed.


Effects of verapamil on automaticity and conduction with particular reference to tachyphylaxis.

Verapamil delivered via the sinus node artery exerted a dose-related, exclusively negative chronotropic action at all concentrations studied. Perfusion through the AV node artery during AV junctional rhythm also caused a dose-related negative chronotropic response, but the concentrations required to depress this pacemaker were ten times higher than those required to depress sinus node automaticity. Verapamil administered into the AV node artery during sinus rhythm impaired AV conduction. His bundle electrograms demonstrated that depressed A-V conduction was exclusively located at the A-H level. In 5 out of 10 dogs verapamil (5 to 10 mg) delivered into the septal artery caused an abrupt onset of ventricular fibrillation without premonitory dysrhythmias. Verapamil (except at very high concentrations) did not alter the responsiveness of the sinus node and the AV junction to acetylcholine or norepinephrine, whether administered selectively into the sinus node artery or the AV node artery or released by neural stimulation. Serial injections of verapamil were associated with tachyphylaxis for the direct chronotropic and dromotropic properties of the drug.


Programmed simultaneous biventricular stimulation in man, with special reference to its use in the evaluation of intraventricular reentry.

Programmed stimulation was alternatively performed exclusively from the right ventricular endocardium, exclusively from the left ventricular epicardium and simultaneously from both ventricles in 8 patients who did not have coronary artery disease or bundle branch block. A specially constructed QRS triggered pacemaker, (with a refractory period of 260 msec and an escape interval of 800 msec) connected to the right ventricular and left ventricular electrodes, was used to perform simultaneous biventricular stimulation. The latter had no untoward effects and was not more dangerous than exclusive right ventricular, or exclusive left ventricular, stimulation. In 3 patients, pacemaker-induced repetitive firing occurred during right and left ventricular pacing. Persistence of this phenomenon (in these 3 patients) during simultaneous biventricular stimulation is in keeping either with a microreentry occurring in the vicinity of the electrodes or with a macroreentry involving the bundle branches. A more precise evaluation of the reentry circuit requires that left ventricular pacing be performed from an endocardial (rather than from an epicardial) site. This study suggests that the pulse generator described in the present communication can be used to produce simultaneous atrial and ventricular activation (or pacing) by connecting one pole to an atrial electrode and the other pole to a ventricular electrode. This modality of stimulation can be effective in preventing or abolishing some types of reciprocating atrioventricular tachycardias.


Blood cadmium and plasma zinc measurements in acute myocardial infarction.

Blood cadmium and plasma zinc were measured in a series of 47 patients admitted for myocardial infarction (MI) and in 37 control subjects divided into 3 groups. Certainly increased blood cadmium values, for the MI patients, were found in 33%. The mean blood cadmium value of the MI series was significantly (P less than 0.001), but not invariably, higher against the control subjects. The difference between the zinc values of the series was studied in 35 MI patients with raised serum enzyme activity. In MI patients, the mean plasma zinc content was significantly (0.001 less than P less than 0.01) lower than in healthy controls. Of the enzymes, the highest positive correlation was found between the ratio of blood cadmium to plasma zinc and the GOT activity. Of the ratio, the MI patients had values in excess of the controls range in 43%, and values within the limits of the healthy controls in 40%. Therefore, the rise in the ratio is of limited value for the diagnosis of myocardial infarction in an individual patient.


Serial echocardiography during the first 3 mth of life in normal neonates.

Echocardiography was performed in 13 normal neonates on the first day of life and repeated after 1 wk, 1 mth and 3 mth. Measurements were made of cardiac chamber size and wall thickness, mitral, tricuspid and pulmonary valve motion, right and left ventricular systolic time intervals, and of fractional left ventricular shortening (%deltaS) and mean velocity of circumferential fibre shortening (mean Vcf). During the study there was a relative decrease in right ventricular cavity size and wall thickness with an increase in the pulmonary valve EF slope, indicating a fall in pulmonary artery pressure with regression of the right ventricle. Left ventricular size and thickness increased while LVET became longer, possibly the consequence of an increasing left ventricular afterload. There was not a significant change in %deltaS and mean Vcf during the study period. The greatest change from right to left ventricular preponderance occurred between 1 wk and 1 mth of life and was accompanied by changes in the mean frontal QRS axis of the electrocardiogram. The study shows that significant changes occur in the echocardiogram during the first 3 mth of life; neonatal echocardiograms should be interpreted not only in relation to the baby's weight, but also to its age.


Syncope and aortic stenosis: significance of conduction abnormalities.

22 patients with syncope and significant aortic stenosis underwent electrophysiological evaluation in addition to the hemodynamic study. Abnormalities of impulse formation or conduction were present in 12 patients. 6 patients demonstrated HV times greater than or equal to 55 msec. There was no correlation between the aortic valve gradient and the HV interval, between the enddiastolic volume of the ventricle and the HV time and between aortic valve calcification and the HV time. Syncopal attacks were corrected with aortic valve replacement even in patients with prolonged HV times.


Oral absorption of cimetidine and its clearance in patients with renal failure.

The plasma concentration curve after a single oral dose of cimetidine 200 mg was followed in 27 patients with varying degrees of chronic renal failure (creatinine clearance 1--52 ml/min) and in 46 patients with normal serum creatinine. Compared to the latter patients, the plasma concentration was higher and the elimination rate was slower in all uraemic subjects, including a group with moderate renal impairment. The preliminary recommendations of dosage for patients with a creatinine clearance below 5 ml/min, and for patients on regular haemodialysis, is cimetidine 200 mg every 12 h, 5-15 ml/min 200 mg every 12 to 8 h, 15-30 ml/min 200 mg every 8 h and 30-52 ml/min 200 mg every 6 h.


Human pharmacokinetics of nitrazepam: effect of age and diseases.

Plasma concentrations of nitrazepam were measured by gas-liquid chromatography in: young healthy volunteers, in geriatric and psychiatric patients and in epileptic children. The disposition of nitrazepam was described in terms of a two-compartment open model. After a single oral dose of nitrazepam 5 mg the most prominent differences between the experimental groups were in the beta-phase half-life mean 29 h in the young volunteers and 40 h in geriatric patients , and in the apparent volume of distribution during the beta-phase of 2.4 vs 4.8 1/kg. Total plasma clearance and the average steady state concentration in both groups were equal. The plasma level rose at a rate proportional to the beta-phase half-life, and so, they were achieved more rapidly in the young than in the old subjects (3.5 vs 7.5 d). No change in steady-state level or in the half-life of nitrazepam were found during long term treatment, which indicates lack of enzyme induction or inhibition. In 95% of the epileptic children with a good to fair clinical response, the plasma concentration of nitrazepam was 40-180 ng/ml (mean 114 ng/ml). As all of the patients were on combined antiepileptic therapy, no attempt was made to correlate plasma level with therapeutic response.


Pharmacokinetics of quinidine related to plasma protein binding in man.

The disposition and plasma protein binding of quinidine after intravenous administration were studied in 13 healthy subjects. Plasma protein binding, expressed as the fraction of quinidine unbound ranged from 0.134--0.303 (mean 0.221). Elimination rate constant (beta) varied from 0.071 to 0.146 h-1 (mean 0.113), and apparent volume of distribution (Vbeta) varied from 1.39--3.20 1 . kg-1 beta (mean 2.27). Total body clearance was 2.32--6.49 ml min-1 . kg-1. There was a positive linear correlation between the plasma fraction of unbound quinidine and both V beta (r = 0.885, p less than 0.01) and total body clearance (r = 0.668, p less than 0.05). No significant correlation existed between the fraction of unbound quinidine in plasma and the elimination rate constant. The results show that both the apparent volume of distribution and total body clearance of quinidine are proportional to the unbound fraction in plasma. This implies that the total plasma concentration of quinidine at steady state will change with alterations in plasma binding, whilst the concentration of unbound compound and its elimination rate will remain unaffected.


Pharmacokinetic, bioavailability and pharmacodynamic study of indobufen (K 3920), an inhibitor of platelet aggregation, after a single dose in man.

Six healthy volunteers received single iv and oral doses of 2-[p-(1-oxo-2-isoindolinyl)phenyl] butyric acid 100 mg (indobufen; K 3920), an inhibitor of platelet aggregation. Plasma levels and urinary excretion of the drug were determined by GLC. Collagen-induced platelet aggregation was assessed turbidimetrically at various intervals after administration. The plasma half-life of the drug was 7--8 h and more than 70% of the administered dose was recovered within 48 h in urine, as unchanged drug and as the glucuronide of indobufen. After oral administration of tablets of two different formulations, the drug was completely absorbed, but one formulation showed faster absorption. The maximal inhibitory effect on platelet aggregation was observed 1 to 4 h after iv administration, and it had decreased by 8h. After tablets, peak effect and the time of the peak were similar, but activity was significantly prolonged, in accordance with the higher plasma levels found at 8 h. The data suggest that the effect of indobufen on platelets is reversible, and that for this drug platelets behave as a compartment that slowly equilibrates with plasma.


Indobufen (K 3920), a new inhibitor of platelet aggregation: effect of food on bioavailability, pharmacokinetic and pharmacodynamic study during repeated oral administration to man.

The effect of food on bioavailability of indobufen tablets was investigated in 6 healthy volunteers. Subsequently, the same subjects took 100 mg b.i.d. for 7 days. Plasma levels and urinary excretion of indobufen were determined by GLC. Platelet aggregation induced by several concentrations of adrenaline was determined turbidimetrically at various times after the first and last doses. The absorption of indobufen tablets was not substantially impaired by the presence of food in the GI tract, although peak plasma levels and AUCs were slightly reduced after food. Pharmacokinetic analysis of plasma and urinary levels of indobufen did not indicate any change in drug disposition after repeated dosing. Adrenaline-induced platelet aggregation was markedly inhibited for up to 12 h after the first dose  and the intensity and duration of this effect did not change after repeated administration. A twice-daily dosing appears suitable for clinical trials.


Inhibition of platelet uptake of serotonin in plasma from patients treated with clomipramine and amitriptyline.

The inhibition of serotonin uptake by platelets has been measured in blood from 20 patients on amitriptyline (50--225 mg daily), 14 patients on clomipramine (25--200 mg daily), and in an untreated group of 21 depressed patients. A complete kinetic analysis was carried out in each patient. Using the increase in the kinetic parameter Km as a measure of uptake inhibition, there was high correlation between the daily dose and inhibition within each drug group, clomipramine being about 10 times more potent than amitriptyline. The inhibition did not vary with age, sex, duration of treatment (up to 3 years), or concomitant use of moderate doses of benzodiazepines, neuroleptics or lithium. In the amitriptyline group the inhibition was significantly smaller in smokers than in non-smokers. The kinetic parameter Vmax was essentially unchanged in the amitriptyline group, and was markedly reduced in the clomipramine group, but without any correlation with dose. The mixed competitive-noncompetitive effect of clomipramine confirms previous in vitro findings.


The protein binding of methotrexate by the serum of normal subjects.

The protein binding of methotrexate by serum from eight normal volunteers was assessed by continuous ultrafiltration at pH 7.4 and 37 degrees C. Methotrexate concentrations were measured by radioimmunoassay and the data analysed by the method of Scatchard. The major binding protein was albumin which bound 87.3% of the drug in serum. Analysis of the Scatchard plots indicated two distinct groups of binding sites. Class I was found to have 0.16 +/- 0.05 (S D) binding sites with an intrinsic association constant of 71.15 +/- 35.98 (S D) X 10(4) M-1: Class II had 2.01 +/- 0.93 (S D) binding sites and and affinity of 0.18 +/- 0.15 X 10(4) M-1. No great change in the percentage of methotrexate bound occurred until the total concentration of the drug exceeded 50 muMol 1-1.


Convulsant, anticonvulsant and anaesthetic barbiturates. 5-Ethyl-5-(3'-methyl-but-2'-enyl)-barbituric acid and related compounds.

Barbiturates derived by minor structural changes to the butenyl sidechain of the convulsant 5-ethyl-5-(3'-methyl-but-2'-enyl)-barbituric acid are almost devoid of convulsant activity, but all have anaesthetic and anticonvulsant effects. Anticonvulsant activity is also observed in the convulsant barbiturate. Increased lipophilic character does not increase anaesthetic potency, only speed of onset, and anticonvulsant activity is reduced in the more lipophilic compounds. The stereochemistry at the 3'-position of the sidechain is vitally important to convulsant activity, and also influences anticonvulsant potency.


Effect of morphine on the accumulation of DOPA after decarboxylase inhibition in the rat.

Acute systemic administration of morphine (10 mg/kg s.c.) to rats increased in vivo tyrosine hydroxylation in the striatum measured as the accumulation of DOPA after decarboxylase inhibition. DOPA accumulation reached a maximum 30-60 min after morphine. The morphine antagonist naloxone (1, 10 or 100 mg/kg s.c.) did not significantly after DOPA accumulation. However, naloxone completely antagonized the effect of morphine. The DA agonist apomorphine decreased and the DA antagonist haloperidol increased DOPA accumulation. The effect of apomorphine (0.05 mg/kg) was counteracted by morphine. Naloxone did not significantly change the accumulation of DOPA  after apomorphine or after haloperidol. In rats treated with gamma-butyrolactone (GBL) or with reserpine DOPA accumulation was not altered by treatment with morphine or naloxone. However, the inhibiting effect of apomorphine (0.5 mg/kg) on the accumulation of DOPA in rats treated with reserpine was weakly counteracted by morphine (0.5 mg/kg) on the accumulation of DOPA in rats treated with reserpine was weakly counteracted by morphine (10 mg/kg s.c.). Since the effects of morphine on the apomorphine-induced inhibition of DOPA  accumulation were antagonized by naloxone, we suggest that the effects on striatal DOPA accumulation produced by morphine were mediated via opioid receptors and not directly via DA receptors.


Similar binding of 3H-ADTN and 3H-apomorphine to calf brain dopamine receptors.

The binding of 3H(+/-)-ADTN (of high specific activity; 7.6 Ci/mmole) to homogenates of calf striatum was investigated. The dissociation constant (KD) for the specific, saturable binding of 3H-(+/-)-ADTN was 1 nM and the density of specific sites was 100 fmoles/mg protein. The IC50 values (nM concentrations inhibiting specific binding by 50%) were 0.9 for (+/-)-N-propyl-norapomorphine, 3.0 for dopamine, 7 for (--)-adrenaline, 60 for (--)-noradrenaline and 4000 for isoproterenol, a series of potencies compatible with properties for a dopaminergic site. The (+)-enantiomer of ADTN was 10 times more potent than (--)-ADTN in competing for 3H-(+/-)-ADTN, while the (--)-enantiomer of 5-OH-dipropyl-ATN was 40 times more potent than the (+)-isomer. The IC50 values for various agonists against 3H-(+/-)-ADTN were similar to those against 3H-apomorphine or 3H-dopamine in the calf striatum. A comparison of these 3H-(+/-)-ADTN data to those for 3H-spiperone suggests that the two 3H-ligands label different receptor sites.


Electrophysiological effects of desipramine on guinea pig papillary muscles.

The effects of desipramine (DMI) in concentrations between 1 x 10(-7) M and 1 x 10(-4) M on various electrophysiological parameters were evaluated in ventricular papillary muscles of guinea pig. At concentrations less than 5 x 10(-5) M, DMI produced a significant shortening in the action potential duration (APD) measured at both 50% and 100% of repolarization. At 1 x 10(-4) M, the terminal portion of repolarization was so prolonged that the total APD was not significantly different from control values. DMI (greater than 1 X 10(-5) M) did not change the resting potential but significantly, decreased the overshoot potential, the amplitude, and the maximum rate of rise of phase O depolarization (Vmax) and shifted the membrane responsiveness and membrane reactivation curves downward and to the right. The effective refractory period (ERP) was shortened or lengthened, the effect being dependent on the concentration, but always made the ERP long relative to APD. DMI, (1 X 10(-5) M and 5 x 10(-5) M), attenuated and abolished the spontaneous activity and the Ca-mediated action potentials induced in ventricular muscle fibers. The mechanisms responsible for DMI's in vivo arrhythmogenic or antiarrhythmic effects are discussed. In terms of changes in ion conductance most effects can be explained by a reduction in sodium and calcium conductance.


Effects of loperamide on the guinea pig taenia coli.

The effects of an antidiarrhoeal agent, loperamide, were studied using isolated guinea pig taenia coli. Loperamide in concentrations ranging from 10(-7) M inhibited the cholinergic, contractile responses induced by electrical transmural stimulation, nicotine and serotonin, and the nonadrenergic, relaxing responses induced by electrical transmural stimulation and nicotine. However, the adrenergic response to perivascular nerve stimulation was not affected by these concentrations. The inhibitory effects of loperamide were not reversed by washing with a drug-free solution. Morphine (10(-6 M to 10(-5) M) also inhibited both cholinergic and nonadrenergic responses, but the effect was reversible. Naloxone (1o(-6) M) attenuated the inhibitory effects of both drugs. Unlike morphine, loperamide in concentrations higher than 5 x 10(-6) M relaxed the strips and reduced the contractile response to acetylcholine noncompetitively, and these effects were not blocked by naloxone. These results suggest that loperamide at low concentrations acts selectively on the opiate receptors located in both cholinergic and nonadrenergic nerves and at higher concentrations also acts directly on smooth muscle thus producing relaxation of the intestinal tone.


Influence of temperature on the sensitivity of the adrenoceptors in the isolated atria of guinea pigs and rats.

The influence of the bath temperature on the responsiveness to sympathomimetic amines was studied with isolated guinea pig and rat atria. In electrically driven guinea pig left atria, the dose-response curve for the positive inotropic effect of isoproterenol (ISO) was shifted to the left by lowering the temperature from 36 to 24 degrees C. The positive inotropic effect of phenylephrine (PHE) in lower concentrations was attenuated by lowering the temperature. Phentolamine markedly inhibited the PHE response at 36 and 32 degrees C, whereas it produced no inhibition at 24 degrees C. Similar changes were observed with rat left atria. In guinea pig left atria, propranolol inhibited the response to PHE more effectively at 24 degrees C than 32 degrees C. With guinea pig and rat atria the dose--response curve for the positive inotropic effect of PHE in the presence of phentolamine was shifted to the left by lowering the temperature. The results suggest that lowering the temperature of the bath solution diminished the positive inotropic effect of PHE mediated by alpha-adrenoceptors and potentiated that mediated by beta-adrenoceptors.


Terbutaline and adrenaline inhibit leakage of fluid and protein in guinea-pig lung.

The effect of terbutaline (0.3 mg/kg s.c.) and adrenaline (0.1 and 0.3 mg/kg s.c.) on histamine--aerosol-induced increase in lung weight and dye content was studied in conscious guinea pigs, previously given Evans blue dye. Both drugs prevented the effects of histamine. It is concluded that terbutaline and adrenaline have a pronounced anti-permeability effect in guinea-pig lungs inhibiting the histamine-induced microvascular efflux of fluid and protein.


Effect of intragastric acid on pepsinogen secretion in the rat.

When the osmolarity of intragastric instillates was constant (200 mosmole/l) the changes in their hydrogen ion concentrations (maximally from 0.01 to 100 mM) did not significantly affect pepsinogen secretion in anaesthetised rats. Solutions of 100 mM HCl, 100 mM NaCl and 150 mM sucrose all produced a similar stimulation of pepsinogen secretion. The results do not support the view that the gastric mucosa contains receptors sensitive to hydrogen ions regulating pepsinogen secretion under physiological conditions.


Lack of effect of levallorphan on analgesia induced by intraventricular application of porcine calcitonin in mice.

Intraventricular administration to mice porcine calcitonin (10 U/kg) as well as of morphine (3 microgram/kg) elevated the threshold pressure of stimuli applied to the base of the tail as assessed by squeaking, struggling or biting, all of which were regarded as manifestations of pain sensation in the animals. Pretreatment with an opiate antagonist, levallorphan (30 mg/kg i.p.) showed no influence upon the analgesic effect of calcitonin, though it completely antagonized the effect of morphine. The results suggested that a peptide hormone, calcitonin, exerted its analgesic action in a manner distinct from the narcotic analgesic.


3H-Spiroperidol binding to dopamine receptors in rat striatal membranes: influence of loxapine and its hydroxylated metabolites.

The effects of loxapine and its hydroxylated metabolites 7-hydroxyloxapine and 8-hydroxyloxapine on 3H-spiroperidol binding to rat striatal membranes were investigated. Whereas 7-hydroxyloxapine and loxapine displayed strong affinities for 3H-spiroperidol binding sites, 8-hydroxyloxapine was essentially inactive. The potency of 7-hydroxyloxapine to displace 3H-spiroperidol is 1.5 times and 8 times those of haloperidol and chlorpromazine, respectively. These results suggest that the combined effects of loxapine and 7-hydroxyloxapine on the postsynaptic dopamine receptors in the brain may explain the clinical efficacy of loxapine in the treatment of schizophrenia.


The effects of levodopa on plasma glucose in two strains of rat.

The effects of levodopa on plasma glucose were examined in two strains of rats. In fasted Wistar rats levodopa produced a dose-dependent hyperglycaemic response which was augmented by pretreatment with nialamide. This response in nialamide-treated rats was prevented by pretreatment with phentolamine and converted to a hypoglycaemic response. Phentolamine increased the plasma concentration of immunoreactive insulin (IRI). In phentolamine-pretreated rats levodopa produced a further marked increase in the plasma IRI concentration. It is suggested that the prevention of levodopa hyperglycaemia by phentolamine is due to the marked increase in the plasma IRI concentration produced by pretreatment with phentolamine. Moreover the fall in the plasma glucose concentration produced by levodopa in phentolamine-pretreated rats is likely to be due, at least in part, to the additional increase in the plasma IRI concentration produced by levodopa under these conditions. In contrast, in fasted Sprague-Dawley rats pretreated with nialamide, levodopa produced either no effect on plasma glucose, or in larger doses, a marked hypoglycaemic effect followed by death. This hypoglycaemic effect was accompanied by a decrease in the plasma IRI concentration.


Alteration of GABA metabolism in mammalian brain by l-alpha-amino-beta-chloropropionic acid hydroxamide and related compounds.

The administration of L-alpha-amino-beta-chloropropionic acid hydroxamide (L-ACPH) to mice brought about an inhibition in GABA-T activity in the brain of the animals, a significant inhibition occurring with dosage levels as low as 0.25 mmol/kg. Minimum levels of GABA-T activity were reached 3 h after administration of the drug. Brain glutamic acid decarboxylase, DOPA decarboxylase and aspartate aminotransferase activities were not altered by the L-ACPH but alanine aminotransferase activity was totally inhibited. Slight changes in structure caused great changes in the potency of the drugs. For example, the elongation of the L-ACPH structure by one carbon, or a change in the configuration of the amino group from L- to D-, caused a significant decrease in GABA inhibition. The chloro and hydroxamide groups were necessary for inhibitory activity. The administration of L-ACPH to mice delayed the onset of drug induced seizures but had a less noticeable effect against maximal electroshock. The addition of L-ACPH to crude extracts from brain, or to preparations of semipurified GABA-T, also inhibited GABA-T activity. Again the development of the inhibition was time-dependent. Possible mechanisms of action with respect to L-ACPH induced inhibition of GABA-T activity are discussed in the light of the data presented.


Effect of 6-hydroxydopamine on blood pressure and heart rate responses to intracisternal clonidine in conscious rabbits.

The effects of intracisternal injection (i.c.i.) of clonidine (1 microgram kg-1) on blood pressure and heart rate were studied in conscious rabbits with an implanted catheter in the cisterna magna. Each animal was studied under control conditions and 7 days after i.c.i. of 6-hydroxydopamine (6-OHDA) (1 microgram kg-1; n = 10) or ascorbic acid vehicle (n = 6). In the control experiments blood pressure and heart rate began to fall 1--2 min after i.c.i. of clonidine, with maximum falls at 10--20 min averaging 18 +/- 2 mmHg and 45 +/- 8 b/min and almost complete recovery by 90 min. After vehicle pretreatment neither response was significantly altered. After 6-OHDA the early component of the bradycardia was abolished and only a late fall in heart rate developed 30 min after i.c.i. clonidine. The magnitude of the hypotension was unaffected but the onset was slightly delayed, probably owing to the abolition of the bradycardia. The dose of 6-OHDA reduced spinal cord catecholamines to about 20% of the level observed after vehicle. Central catecholaminergic pathways are thus important in the early predominantly vagal component of the clonidine induced bradycardia, but play little role in the hypotensive response.


Influence of histamine on the serotonergic system of rat brain.

Both histamine and 4-methylhistamine, after intraventricular injection into normal rats, reduced the levels of serotonin and increased those of 5-hydroxyindoleacetic acid in hypothalamus; after injection into tranylcypromine-treated rats, head twitches were induced which were blocked by antiserotonin agents. 2-Pyridylethylamine, an agonist of histamine H1 receptors, neither influenced serotonin level in hypothalamus nor evoked behavioural changes. It is concluded that injected histamine may release serotonin from the hypothalamus and that this produces the behavioural changes.


Topical clonidine produces mydriasis by a central nervous system action.

One drop of clonidine solution (0.125, 0.25 or 0.5%) was administered topically to one eye in cats anesthetized with pentobarbital in which the vagosympathetic nerves had been sectioned. Clonidine caused a simultaneous dose-related mydriasis in both eyes along with a decrease in heart rate. The peak effects were observed in about 20--30 min. Topical administration of clonidine (0.5%) produced no effect on the parasympathectomized, eserinized iris but did dilate the opposite pupil. Epinephrine (0.1--30 microgram, i.a.) produced equal pupillary dilation in both eyes. In addition, topical clonidine caused a dramatic decrease in postganglionic ciliary nerve activity. All of the effects of clonidine were antagonized by yohimbine (0.5 mg/kg, i.v.). These results demonstrate that topical administration of clonidine causes my driasis in the cat and that this effect is mediated totally by means of CNS inhibition of parasympathetic tone to the iris.


Mianserin potentiates responses to acetylcholine in the rat anococcygeus muscle.

In the rat anococcygeus muscle, mianserin (1 and 10 muM) increased the magnitude of the maximal contractile responses to acetylcholine and carbamylcholine without affecting the maximal responses to (--)-noradrenaline. The potentiating effect of mianserin on responses to acetylcholine was maintained in the presence of 5muM phentolamine, following 6-hydroxy dopamine incubation of the tissues (1 mM for 3h) and in the presence of 1 muM nortriptyline. It is suggested that mianserin increases the sensitivity to acetylcholine by an action at the level of, or distal to, the cholinergic receptor.


Brain distribution of propranolol in the rat.

The distribution and kinetics of D,L-propranolol in rat brain were examined after an intravenous injection of the drug. Measurements in brain areas and blood were performed by means of a sensitive and specific gas liquid chromatographic method. The disappearance rate in cortical areas paralleled that in blood. However D,L-propranolol decreased at a slower rate in hypothalamic and medullary nuclei. Since propranolol is believed to have central hypotensive effects, its retention by certain central nuclei involved in blood pressure regulation is of interest.


Cat phrenic nucleus architecture as revealed by horseradish peroxidase mapping.

Cat phrenic motoneurons, labeled by intradiaphragmatic injection of horseradish peroxidase, formed a tight cluster in the most ventral portion of the ventral horn in lamina IX of the lower cervical cord. Cell counts were symmetrically distributed for 17 to 21 mm along the longitudinal axis of the cord with a unimodal peak at the junction of segments C5 and C6. The phrenic nucleus was bilaterally organized on either side of the cord with anatomical symmetry and in no case was there evidence for the crossing of phrenic axons in the cord. Assessment of cellular geometry and intercellular relationships demonstrated that phrenic cell diameters approximated a normal distribution with a single peak at 26 mum while longitudinal cell lengths average 76 mum. Cells of different size were mixed randomly at all levels of the nucleus. The minimum distance between cells was about 10 mum and the maximum cell packing density approached 2 cells per 10(6) mum3. The results confirm the location of the cat phrenic nucleus, extend the knowledge of phrenic motoneuronal geometry, and provide an anatomical basis for the understanding of recruitment and synchronization phenomena within the phrenic nucleus.


Effects of inertial load and velocity on the braking process of voluntary limb movements.

The aim of this study has been to identify, in humans, the braking process underlying voluntary forearm movements performed at various velocities and amplitudes and against differential inertial loads. The procedure used to estimate the parameters of the braking process involved kinematic analysis of the movement and measurement of alpha-motoneural input to flexor and extensor muscles by recording electromyographic (EMG) activity. We have shown that when the agonist force does not exceed the passive viscoelastic tension developed by the extensor and flexor muscles, the movement can be braked by the viscoelastic forces alone. In contrast, above this force threshold, it was found that the motor output in agonist and antagonist muscles consists of well defined bursts of EMG activity, first in agonist then in antagonist muscles. The timing of these two bursts (duration of the agonist activity and onset of the antagonist activity) are clearly correlated with the value of the peak velocity. For the same peak velocity, the addition of inertial loads increase the excitation level of both agonist and antagonist muscles but does not change the timing of the EMG bursts. The discussion of these results focuses on the concept of "unit of movement" organized to reduce the large number of possible patterns of activation of the muscles acting on the same joint.


Collicular function in human vision.

Threshold elevation in the periphery of the visual field as a consequence of repetitive stimulation can be abolished by stimulating a mirror-symmetric position in the contralateral visual half-field. A patient suffering from a congenital malformation of the right superior colliculus did not exhibit threshold elevation when stimulated repeatedly in the left visual field. Stimulation in the right visual half-field resulted in the usually observed threshold elevation, but stimulating a mirror-symmetric position in the left visual half-field did not abolish threshold elevation in the right half-field. These observations suggest that: (a) threshold elevation probably occurs as a consequence of collicular adaptation and (b) the mirror-symmetrically organized interhemispheric interaction is mediated at the collicular level.


A correlation of receptive field properties with conduction velocity of cells in the rat's retino-geniculo-cortical pathway.

1. The receptive field properties and responses to electrical stimulation of 126 P-cells recorded from the dorsal lateral geniculate nucleus (LGNd) were studied in the hooded rat. 2. Eighty-five cells had a concentric (Kuffler, 1953) receptive field organisation (46 off-centre on-surround; 39 on-centre off-surround). Of the remaining cells 29 had co-extensive on/off excitatory discharge regions, nine had on-centres with suppressive surrounds and two cells gave on-responses but had no suppressive surround. One cell was identified as suppressed-by-contrast. 3. On the basis of the battery of tests developed for the identification of cell types in the cat's retina and LGNd, 35 of the cells with a Kuffler-type receptive field organisation were identified as Y-like. The majority of the remaining cells, both concentric and others, reminded us of the different subclasses of W-cells of the cat. Nine concentric cells in most of the tests exhibited X-like properties. 4. All of the Y-like cells were driven by relatively fast conducting retinal ganglion cell axons, comprising the t1 conduction velocity group. The majority of the remaining cells were driven by slower axons comprising t2 or t3 conduction velocity groups. 5. Thus, in the rat, as in other mammalian species studied so far, there is a correlation between the conduction velocity groups in the retino-geniculo-cortical pathway and the functional groups based on the cells' receptive field properties. There seem to be functional equivalents of the cat's Y- and W-cell classes but evidence for a distinct X-like class of cells is lacking.


The retinal origin of uncrossed optic nerve fibres in rats and their role in visual discrimination.

An attempt was made to sever the optic chiasma in the mid-sagittal plane in 12 rats. This was successful in 8 animals. Provided there was no additional substantial damage to the uncrossed optic fibres the rats were able to relearn an intensity discrimination and to learn or relearn an orientation discrimination, although optokinetic following was abolished. The results unequivocally demonstrate that the uncrossed optic fibres can mediate two kinds of visual discrimination. The area of retina giving rise to the uncrossed fibres was determined from the position of undegenerated retinal ganglion cells in each eye following section of the chiasma, and in one eye of 4 rats in which one optic tract was entirely or extensively destroyed. The ganglion cells giving rise to the uncrossed optic fibres occupy about 40 degrees of the temporal retina, corresponding to the binocular overlap in the visual field.


The projection of the temporal retina in rats, studied by retrograde transport of horseradish peroxidase.

Horseradish peroxidase (HRP) was injected unilaterally into the lateral geniculate nucleus or tectum, or both, in 26 hooded rats in order to mark the exact extent of the retina from which uncrossed optic axons arise. This region occupied about a quarter of the retina, in the temporal periphery, following thalamic injections, but a much smaller region following tectal injections. By comparing the proportions of HRP positive neurones in nasal and temporal retinae of both eyes it was shown that: (1) within the region supplying uncrossed axons the majority of the ganglion cells nevertheless project contralaterally, (2) a large proportion of the ganglion cells from the temporal crescent project bilaterally, which does not occur from the remainder of the retina, (3) ganglion cells of all sizes contribute to both ipsilateral and contralateral projections. The results also support earlier suggestions that the smallest neurones in the ganglion cell layer do not send an axon into the brain, and are therefore not ganglion cells.


Thermosensory defects after cervical spinal cord lesions in the cat.

The behavioural thermosensitivity of cat paws was examined before and/or after restricted uni- and/or bilateral lesions had been made in the spinal cord between the first and fifth cervical segments. Unilateral lesions of the lateral funiculus, which involved at least its whole width at the level of the central canal, reproducibly were found to interfere with the contralateral sensitivity for temperature increases and/or decreases. No corresponding thermosensory deficiencies were found after unilateral lesions involving the ventral spinal quadrant or the dorsal funiculus. Various bilateral and combined lesions were made, but no cat ever developed thermoanaesthesia. The bilateral lesions included bilateral transections of: the middle parts of the lateral funiculi, the dorsal halves of the lateral funiculi, the dorsal funiculi, and the ventral spinal half. Most of our knowledge about peripheral behavioural thermosensitivity after spinal cord injury is based on observations of human patients, especially after anterolateral chordotomies. The present finding of contralateral thermosensory deficiencies after lesions of the middle part of the lateral funiculus fits with some of the clinical reports. The present failure to cause thermoanaesthesia, on the other hand, is inconsistent with the theory of a single ascending spinal pathway for behavioural thermosensitivity, which has emanated mainly from the clinical observations.


A comparison of visual responses in two pretectal nuclei and in the superior colliculus of the cat.

Single unit recordings from 220 units were obtained from the nuclei praetectalis anterior (NPA) and posterior (NPP) of 30 immobilized, anesthetized cats. Quantitative analysis of pretectal (PT) visual activity was mainly based on recordings from the NPP. For comparison, 160 collicular (CS) neurons were studied. A strong sensitivity for moving objects was evident in both samples. The following main types of PT activity were categorized: (A) slow movement, direction-selective units (21%); (B) slow movement, nondirection-selective units (19%); (C) units nonselective for stimulus velocity and direction (24%); (D) jerk movement selective, nondirection-selective units (36%). Latency measurements following single shocks to optic chiasm (OX) and tract (OT) showed mainly slow conducting fiber input to the PT and CS which can be divided into two different groups by conduction properties and synaptic delay: direct W-input and delayed W-input. Fast Y-fiber input of both types, direct and indirect, was recorded at both sites, PT and CS.


Morphological evidence for axonal sprouting of cerebellothalamic neurons in kittens after neonatal hemicerebellectomy.

Changes in cerebellothalamic projections in kittens after neonatal hemicerebellectomy were studied by the retrograde and anterograde horseradish peroxidase (HRP)-tract-tracing methods. The number of cerebellar nuclear neurons labeled retrogradely with HRP injected into the ipsilateral VA-VL complex of the thalamus was much more numerous in neonatally hemicerebellectomized kittens than in intact kittens. Presumed terminals of ipsilateral cerebellothalamic fibers labeled anterogradely with HRP injected into the cerebellar nuclei were also distributed more densely and extensively in the thalamic areas, especially in the VA-VL complex, of hemicerebellectomized kittens than in the thalamic areas of the control kittens. These results are in good accordance with those obtained from the previous electrophysiological study (Kawaguchi et al., 1979) and offer corroborating evidence for axonal sprouting of cerebellothalamic neurons after neonatal hemicerebellectomy.


Amblyopia occurs in retinal ganglion cells in cats reared with convergent squint without alternating fixation.

The spatial resolving power, contrast sensitivity, and receptive field properties of retinal ganglion cells were studied in cats reared with either convergent or divergent squint in one eye. Sustained-X cells in the area centralis of the squinting eye of the cats with esotropia without alternating fixation showed significantly poorer spatial resolution, and reduced contrast sensitivity compared with cells in the area centralis of the normal eye. These amblyopic sustained-X cells in the area centralis of the squinting eye had receptive field characteristics similar to those found in immature cells of young kittens. They had a shallow sensitivity gradient within a relatively widespread centre zone and a weak and widespread inhibitory surround. In contrast, the sustained cells in the area centralis of the normal eye revealed a typical, well defined, small centre zone with its sensitivity gradient extremely steep and its inhibitory surround strong and confined. A minor degree of amblyopia was also found in transient Y-cells in the area centralis of the squinting eye of these cats. However, no loss of resolving power was found in the cells in the area centralis of the squinting eye of the cats with esotropia or exotropia which showed alternating fixation. Thus, amblyopia occurs in those eyes which have lost the use of the area centralis as the normal visual axis during early postnatal development, and its organic lesion is already apparent in the retinal ganglion cells--the third order neurone in the afferent visual system. It is suggested that the loss of the ability to fixate results in inadequate stimulation of the central retinal ganglion cells due to the habitual presence of blurred images at the area centralis which prevents their full development during the critical period.


Family size, contraceptive practice and fertility intentions in England and Wales, 1967--1975.

In Britain, as in the United States over the last decade, there has been a considerable decline in the birthrate, in average family size and in the number of children wanted, at the same time that use of the most effective forms of contraception--the pill, the IUD and contraceptive sterilization--and use of abortion have become more and more widespread.


Ecosystemic epistemology: an alternative paradigm for diagnosis.

An alternative paradigm for diagnosis based on cybernetics, ecology, and systems theory is proposed. This paradigm, termed "ecosystemic epistemology," suggests that diagnosis focus on knowing problematic situations in an ecological and systemic way. Theoretical statements concerning this approach are delineated with specific references to major family therapists. This discussion provides a foundation for an ecosystemic epistemology for diagnosis that addresses the following issues: (a) the meaning of system; (b) the symptom's presence in the system; (c) the therapist's presence in the system; (d) the ecological relationship system that emerges in diagnosis; and (e) the relation between ecosystemic epistemology and the process of diagnosis. In effect, this paper attempts to formally describe the underlying epistemology inherent in the work of therapists who approach diagnosis in an ecological and systemic way.


The family therapy of attempted suicide.

Suicidal behavior is a multidetermined act based upon a variety of factors among which family tensions and patterns of interaction predominate. Family therapy, nevertheless, is underutilized for suicidal situations because too few practitioners possess the requisite skills in both suicidology and family treatment. This paper attempts to integrate the two fields, describes some assessment procedures, and presents an account of the method of family therapy utilized by the author with suicidal persons. The basic goals of therapy are to help initiate and to catalyze a healing process that will enable the participants to accept changes in both individual and family existence; to decrease the amount of destructive family interaction; to deal with the inevitable anxiety that accompanies growth and development; to make contact with and among the family members; and to provide hope.


Family awareness for nonclinicians: participation in a simulated family as a teaching technique.

This paper describes a course in family theory geared to "well" family members that combines didactic and experiential teaching techniques. A key feature of the course is that students participate in a simulated family for twelve weeks. Family therapists are skilled at using techniques that powerfully dramatize family process; they can provide a needed and useful service to the community by teaching the dynamics of families functioning to people who have a personal or professional interest in learning more about families.


Jealousy: systematic, problem-solving therapy with couples.

Literature on the treatment of marital jealousy has focused on individual and interpersonal awareness/insight and the use of communication-negotiation skills. This paper proposes an alternative viewpoint applying the problem-solving approaches of Erikson, Haley, Watzlawick, Weakland, and Fisch to the alteration of jealous systems. Through a detailed case study, the author describes the concept of the therapeutic triangle and the use of paradox and symptom transfer as potential contributions in the treatment of jealousy. Finally, the author discusses briefly a possible factor leading to the success of the systematic, problem-solving modality: serious playfulness.


Pilgrim's progress III: A trend analysis of family theory and methodology.

Exciting developments in family theory construction over the past few years demand a constant survey and evaluation of measurable progress. This paper documents some developmental trends that have taken place in family theory construction and its applications, as well as in the relation of theory to advances in methodology. Many of these trends are examined in the light of two earlier reports, Pilgrim's Progress I (21) and Pilgrim's Progress II (13).


An empirical comparison of natural-father and stepfather family systems.

This study examined the family system differences between 40 volunteer natural-father and stepfather families. Family triads consisting of the husband, the wife, and a child whose age ranged from 12 to 15 years were studied. Four instruments were used: (a) the Family Concept Q-Sort; (b) a Semantic Differential; (c) a demographic questionnaire; and (d) an interaction-reaction questionnaire. Analyses of variance on the data obtained from the Q-sorts and the Semantic Differentials indicated that stepfather family systems are different from natural-father family systems along several salient dimensions including psychological adjustment, satisfaction with family, reciprocal understanding, and perceived goodness and potency. It was concluded that the differences between the family systems in terms of their interpersonal relations and perceptions affect the entire stepparent family system and its ability to function adequately.


Remarriage after divorce: dissolution and reconstruction of family boundaries.

Remarriage is analyzed from the perspective of family boundaries and roles. The nuclear and remarriage family models are compared, and the process that begins with the formation of the first-marriage nuclear family and ends with the formation of a second-marriage family is conceptualized in terms of changing family boundaries and roles. Discussions with remarriage group members provide concrete illustrations of this process and suggest solutions to some of the problems confronting remarriage family members.


The pill and mortality from cardiovascular disease: another look.

Analysis of U.S. mortality statistics shows that since adoption of the pill, deaths among women of reproductive age from cardiovascular diseases have declined much more steeply than have death rates for comparable men. This suggests that the high level of risk of death from such diseases associated with pill use in other studies are exaggerated.


The brain renin-angiotensin system: a critical analysis.

The concept of a brain renin-angiotensin system originated with the observation that the components necessary for the formation of angiotensin II are present in the central nervous system. This observation has been confirmed and extended, and it is now frequently assumed that there is a functional brain renin-angiotensin system. However, careful analysis of the available evidence has revealed a number of significant problems. It appears that most of the renin-like activity measured in extracts of brain is due to the acid protease cathepsin D; this is unlikely to function as an angiotensin-forming enzyme in vivo. Experiments involving central administration of renin substrate have not provided convincing evidence for a significant renin-renin substrate interaction in vivo. Attempts to demonstrate the presence of angiotensin in the brain have been plagued with problems of specificity and it is still not clear if the peptide is actually present in the central nervous system. These problems do not rule out the possibility that there is a brain renin-angiotensin system, but more definitive evidence is required before it can be concluded that such a tensin system exists.


Interrelations between vasopressin and the renin-angiotensin system.

The interrelationships between vasopressin and the renin-angiotensin system are reviewed. Vasopressin can inhibit the release of renin by the kidney. This effect can occur at physiological plasma concentrations of vasopressin. Centrally administered angiotensin II can stimulate the release of vasopressin, a response that may be partially mediated by brain prostaglandins. The significance of this action of angiotensin II depends on whether there is an effective brain renin-angiotensin system and on whether peripherally generated or administered angiotensin can reach sites in the brain where it can act on vasopressin release. Peripherally administered angiotensin II can under certain, but not all, conditions stimulate vasopressin release. Peripheral angiotensin II can also potentiate the vasopressin response to an osmotic stimulus and to dehydration, but has little effect the release of vasopressin and renin, there is a failure to demonstrate any correlation between the two. Blockade of the renin-angiotensin system fails to modify the vasopressin response to a reduction in blood volume. In conclusion, the physiological significance of the interactions between the vasopressin and the renin-angiotensin system is not as yet clearly established.


Physiological actions of angiotensin II on the kidney.

The importance of angiotensin as a modulator of renal function is well documented. Several lines of evidence suggest strongly that angiotensin plays an important role in the maintenance of renal vascular resistance and arterial pressure in several physiological and pathophysiological states with increased activity of the renin-angiotensin system. Angiotensin also acts as a physiological "brake" on excessive release of renin from juxtaglomerular cells. Angiotensin influences renal sodium excretion via its renal vascular actions to change the glomerular filtration rate and, thus, the filtered load of sodium; in addition, angiotensin influences tubular reabsorption of sodium by altering the filtration fraction and the balance of Starling forces in the peritubular capillaries.


Some contributions to the chemistry of the gastrointestinal hormones.

Twenty-five years ago we described an extraction procedure for porcine secretin in which the intestinal tissue is briefly boiled in water and then extracted with dilute acid at low temperature. Boiling in water, which inactivates proteolytic enzymes, does not extract secretin, and extraction with acid in the cold will minimize cleavage of acid labile peptide structures. This extraction procedure has formed the basis for the isolation not only of secretin but also of cholecystokinin-pancreozymin (CCK) and, in collaboration with other laboratories, of the vasoactive intestinal peptide (VIP), the gastric inhibitory peptide (GIP), and motilin. Recently it has been used for the isolation of an N-terminally extended somatostatin from intestinal tissue, and of a peptide, from both nonantral gastric and intestinal tissues, with gastrin-releasing and probably cholecystokinin-releasing properties. A technique has been worked out permitting the chemical analysis, in certain cases, of polypeptide hormones in the presence of other polypeptides, the polypeptide mixture being exposed to fragmentation conditions known to result in characteristic hormone fragments, which are then extracted and quantitated. The technique can also be useful for the isolation of previously unknown peptides by identifying fragments of such and tracing them back to their peptides of origin.


Bombesin-like peptides in mammals.

Acid extracts of rat gut and brain contain substances that cross-react in a radioimmunoassay for the amphibian skin tetradecapeptide bombesin. Highest concentrations are present in the fundic part of the stomach, but there are significant amounts throughout the small and large intestine. Concentrations in the brain are highest in the hypothalamus. On gel filtration the rat bombesin-like immunoreactivity eluted as two major peaks. Fractionation of the second peak on cation exchange chromatography resolves this material into two further components. Intravenous infusions of partially purified preparations of the two components separated on gel filtration cause increases in serum gastrin in rats that are similar to those produced by immunochemically comparable amounts of synthetic bombesin.


Chemical messengers: a view from the gut.

The peptides usually called gastrointestinal hormones belong to a broader group of regulatory substances distributed in many parts of the body and delivered to their targets not only by the blood but also by neural and paracrine paths. The neural, endocrine, and paracrine cells as a group might be called "regulator cells" and the chemical messengers they produce might be called "regulins." Twenty peptides have been isolated from the alimentary tract and pancreas: 12 have been sequenced, 4 have been partially sequenced, and 4 more have been identified only by immunoreactivity. Gastrin, gastric inhibitory peptide, glucagon, insulin, and secretin can be regarded as established hormones that are released into the blood by identified stimuli and produce identified physiological responses. The evidence for the hormonal status of cholecystokinin, pancreatic polypeptide, and motilin is incomplete but suggestive. The possible physiological roles of the other 12 peptides remain to be determined. If specific antagonists of these peptides can be found, they will greatly assist in elucidating the peptides' physiological roles.


Synaptic modulation by substance P.

The phrase "synaptic modulation," to describe a role of neurotropic peptides, has been used in a number of different ways by a number of different investigators. Using the phrase in its original context, i.e. altered (increased or decreased) synaptic excitability without reference to site or mode of action, evidence is presented that substance P modulates synaptic transmission of cat alpha-motoneurons. The effect appears to be biphasic, with low doses inhibiting, and high doses facilitating synaptic transmission.


Inhibition of sperm dilution damage by purified factors from hamster caudal epididymal plasma and by defined diluents.

Sperm dilution damage can be prevented by diluting hamster caudal epididymal (HCE) sperm in HCE plasma, a fluid which had been shown to contain sperm survival factors (SF). Dialysis and ultrafiltration studies demonstrated that SF consisted of both small-molecule and large-molecule components. Several known macromolecules and small molecules could substitute for these factors. Chemically defined diluents were designed that were able to substitute for HCE plasma in the prevention of sperm dilution damage under certain conditions. When the HCE plasma large-molecule component were fractionated by Sephadex G-100 chromatography, three bands of SF activity eluted. One appeared in the void volume ( is greater than 100,000 daltons), one with bovine serum albumin (67,000 daltons), and one at about 35,000 daltons. Two HCE plasma small-molecule components of less than 500 daltons eluted from both Sephadex G-25 and G-15 columns. Proteolysis studies suggested that both the small-molecule and the large-molecule components of HCE plasma may possess peptide bonds.


Ovarian ectopic pregnancy in association with a copper-7 intrauterine device in situ.

A case is reported of a primary ovarian pregnancy in a patient with a Cu-7 intrauterine device. A brief review of the literature on this subject is exposed. As the action of intrauterine devices on the ovulatory mechanism and tubal transport of the ovum is still unknown, further studies should be carried out to explain this association.


Contraceptive practice before and after therapeutic abortion. II. Use-effectiveness of oral contraceptives and intrauterine devices.

Of 180 women who underwent therapeutic abortion in a certain period in 1977, 71.7% were unmarried and 63.9% were unmarried primigravidas. At the first follow-up visit 3 to 6 weeks postabortion 55.0% of the unmarried primigravidas chose oral contraceptives and 43.2% chose intrauterine devices (IUDs). Of the unmarried women, 25.7% chose oral contraceptives and 65.7% chose IUDs. For unmarried primigravidas the 1-year continuation rates for oral contraceptives and IUDs were 83.6% and 93.8%, respectively. For married women the figures were 55.6% for oral contraceptives and 91.3% for IUDs. The differences between use of oral contraceptives and use of IUDs in the two groups of women was not statistically significant. We recorded no contraceptive failure, but three episodes of pelvic inflammatory disease occurred among unmarried primigravidas. The results indicate a high motivation for reliable methods and a high continuation rate following therapeutic abortion. The results may also indicate that oral contraceptives and IUDs represent equivalent methods for both parous and nulliparous women.


The intrauterine device and ovarian pregnancy.

Within a 1-year period, three patients presenting to the University of Chicago, Chicago Lying-In Hospital with a complaint of lower abdominal pain were diagnosed at laparotomy to have ovarian pregnancies according to the criteria of Spiegelberg. All of the patients were at the time using the Copper-7 intrauterine device for contraception. There are now 50 known cases of ovarian pregnancies in patients using the intrauterine device (IUD). The characteristics of these patients do not differ markedly from those previously reported in studies on tubal pregnancies, with and without the IUD, but the presentation of patients tends to be more variable than in tubal pregnancies. The increasing incidence noted here, in a population already known to be particularly prone to pelvic inflammatory disease and therefore ectopic pregnancies in general, lends further credence to a questioning of the desirability of the IUD in such a population.


Müllerian anomalies: a proposed classification. (An analysis of 144 cases).

Hospital and clinic charts for 100 patients with diagnosed Müllerian anomalies were reviewed. Reproductive history, type of therapy, and treatment results for those patients and for another 44 with a history of exposure to diethylstilbestrol and abnormal hysterosalpingographic findings were recorded and evaluated. The anomaly most frequently associated with reproductive failure was the septate uterus. A new classification, based on degree of failure of normal development, was used in separating the anomalies into groups with similar clinical manifestations, treatment, and prognosis for fetal salvage.


Alterations in the organic compounds of vaginal secretions caused by sexual arousal.

The low-molecular weight organic constituents of human vaginal secretions from normally cycling subjects were analyzed both before and after sexual stimulation. Gas chromatography and combined gas chromatography-mass spectrometry were employed in the analyses of the secretions. Consistent increases were noted for a number of the lipid constituents of the secretions, suggesting that they are derived at least in part from the plasma and transude into the vaginal lumen during arousal. In addition, the increases in the concentrations of glycerol and stearic acid with respect to baseline levels were significant (P is equal to and less than 0.05). Compounds which are produced intravaginally appear to decrease in concentration during the arousal interval because of dilution by the transudate. No consistent qualitative changes were noted in the secretion.


A practical, objective approach to the evaluation of sperm and cervical mucus in humans.

Human sperm fertility potential, expressed as a quality index (QI), was evaluated objectively from considerations of sperm velocity, percentage of motile forms, sperm density, and ejaculate volume. Turbidimetry was applied in the quantitation of sperm velocity. High QIs (700) were characteristic of semen samples that were capable of penetrating cervical mucus in capillary tube penetration tests, while low QIs (80) were associated with specimens that did not penetrate mucus. The rate of decline in QI as a function of time postejaculation was determined for samples stored at 37 degrees C and at ambient temperature, providing correction factors for the comparative evaluation of semen samples analyzed at different times. The penetrability of cervical mucus was determined by capillary tube penetration testing. Subsequent chemical analysis of sperm-penetrable and impenetrable samples indicated that the concentrations of mucus nondialyzable solids (NDS), mucins, and soluble proteins were significantly higher in impenetrable specimens. These characteristics were also observed in impenetrable mucus obtained from patients with cervical factor infertility. These studies indicate that it is now feasible to employ mucus [NDS] in the diagnosis of cervical factor infertility and turbidimetry in the evaluation of human sperm quality.


The presence of complement in human cervical mucus and its possible relevance to infertility in women with complement-dependent sperm-immobilizing antibodies.

Full-complement component lytic activity was measured in human midcycle cervical mucus, using a sensitive 51Cr release hemolytic assay. The level measured was 11.5% of the activity of complement in an equal volume of undiluted human serum. The relevance of this level of complement to complement-dependent sperm-immobilizing antibody activity was studied. After 1 hour's incubation with mucus levels of complement, immobilization of about 50% of spermatozoa occurred and after 3 hours' incubation, immobilization of about 70% of spermatozoa occurred.


The role of antiandrogenic action in cyproterone acetate-induced morphologic and biochemical changes in human semen.

Following the daily administration of 10 mg of cyproterone acetate to three normal fertile human volunteers for 12 to 16 weeks, there was a marked decrease in the count, motility, and cervical mucus-penetrating ability of spermatozoa, with a concomitant increase in abnormal and immature forms. The levels of seminal acid phosphatase and glycerylphosphoryl choline were also significantly decreased. Subsequently, concurrent daily administration of 75 mg of mesterolone increased the count, motility, and cervical mucus-penetrating ability of spermatozoa and stimulated the seminal biochemical constituents. The results indicate that the effects of a low dose of cyproterone acetate are due mainly to peripheral androgen deprivation.


Seminal fluid prolactin: studies in normal subjects and in hypergonadotropic oligospermia.

A sensitive radioimmunoassay was developed for the determination of seminal plasma prolactin levels. Prolactin added to normal or oligospermic seminal plasma was fully recoverable, indicating that the seminal plasma of oligospermic patients did not contain interfering substances. A gradient between seminal plasma blood serum prolactin was found in 54 health fertile subjects. No gradient was demonstrable among 13 infertile oligospermic patients who had normal levels of serum testosterone and luteinizing hormone but elevated levels of follicle-stimulating hormone.


Studies on factors in hamster caudal epididymal plasma and other sources which inhibit sperm dilution damage.

We observed that hamster caudal epididymal (HCE) plasma could inhibit dilution damage in HCE sperm. Here it is shown that in the absence of HCE plasma survival factors (SF), dilution of HCE sperm led to apparently simultaneous lysis and loss of motility. However, in the presence of HCE plasma, lysis did not occur when HCE sperm motility was blocked by palytoxin. Using a newly developed microassay for SF, significant amounts of SF activity were detected in dog and bovine caudal epididymal plasma, hamster testes exudate, HCE sperm cytosol, human seminal plasma, hamster and bovine adrenal extracts, hen's egg, and human serum. The SF activity of HCE plasma could tolerate restricted periods of boiling or pH extremes but was destroyed by trypsin and protease. Unlike human serum, HCE plasma did not significantly alter HCE sperm respiration or ATP content.


[Effect of strychnine and picrotoxin on the development of habituation in the visceral analyzer].

Effects of strychnine and picrotoxin on habituation of cortical potentials evoked by repeated stimulation of the splanchnic nerve were studied in anesthetized and immobilized cats. I. v. administration of strychnine (o.1 mg/kg) or picrotoxin (0.4 mg/kg) did not alter the decrement in evoked potentials. Larger doses of strychnine (0.3 or 0.6 mg/kg) and picrotoxin (0.8 or 2.0 mg/kg) did not block the habituation effects either. Picrotoxin applied to 2nd somatosensory area of the cortex effected amplitude of the negative component of the evoked potentials. Possible mechanisms of the habituation process are discussed.


[Interaction of callosal and extracallosal systems].

Studies of the topography of homotopic transcommissural evoked potentials in 85 symmetrical points of the cat motor cortex, prior to and after section of the corpus callosum, revealed the functional areas as follows: acommissural (53% of the total area), purely callosal (23%), mixed (22%), and purely extracallosal (2%). The summation and reciprocal interrelationships between the callosal and extracion flows spreading over the extracallosal system.


[Patterns of afferent signal convergence in the neurons of the frog midbrain tectum].

The activity of 168 optic tectum units was recorded in conditions of separate and combined actions of light, sound, and pain stimuli. The sensitivity of the neurons to multisensory convergence depended on their spontaneous activity. Excitatory--inhibitory characteristics of responses to unspecific stimuli in most cases were similar to specific responses. Combined action of different stimuli complicated and increased the number of response types.


[Convergence of sensory and cortical inputs on caudate nucleus neurons].

The immobilized cats, the influences of 2nd somatosensory and temporal areas on responses of the caudate nucleus' neurons to stimulation of the tibial and splanchnic nerves, were studied. The majority of spontaneously active neurons responded to the cortical stimulation, mainly from the 2nd somatosensory area. Over half of the neurons revealed the "binareal" feature. The typical form of interaction of the cortical and sensory stimuli (with the 50-msec interval between the conditioning and the testing stimuli) was either partial or complete suppression of responses of the caudate neurons both to the somatic and to the visceral stimulation. The results of cortico-sensory interaction were independent of the nature and functional significance of the stimulated cortical areas.


[Responses of cat pulvinar neurons to stationary visual stimuli].

The activity of 130 neurons in pulvinar was investigated using static visual stimuli (light spots of different dimensions flashing in the center of receptive fields, and diffuse flashing light). 50 neurons of 130 did not respond to light stimuli but only to the movement of black stimuli. The majority of investigated neurons revealed "on--off" types of reactions to the flashing light spot, 14 neurons gave "on" responses, and 28 -- "off" responses. The receptive fields of pulvinar neurons had mainly homogenous structure without center and antagonistic surrounding, although some of them appeared to have concentric type of receptive fields. Some neurons revealed responses similar to those of neurons in the Clare--Bishop area. The responses of such neurons were the regular bursts of discharges during the time of stimulation which suggests the compound structure of receptive field with elements of different latency.


[Inhibition and space-frequency characteristics of the complex receptive fields of the cat visual cortex].

Responses of complex receptive fields of the cat straitum to moving sinusoidal grating were studied. Stimulation of the receptive field with some spatial frequencies suppresses spontaneous discharges. Responses of the receptive field corroborate previously made predictions that the spatial--frequency characteristics of the receptive field should have the main and the secondary maximums and negative areas in case the complex fields perform piece-wise Fourier--transformation of image. The changes of impulse frequency in field's response are predicted by comparing the changes of instantaneous spectrum of grating entering the field with spatial frequency characteristic of the field. The data evidence that the complex field is rather a spatial--frequency filter than a detector. Some complex fields reveal a lateral inhibitory area behind the field's nucleus in direction of stimulus movement. The complex fields with no lateral inhibitory areas seem to serve for piece Fourier--description of image, those with lateral areas--for picking out the countour between textures.


[Coding visual information in frogs by means of the latent periods of neuronal responses].

The difference between latencies of responses of the retina ganglionic cells and the neurons of the midbrain tectum in frogs seems to be a way of coding visual signals which indicates the probability of the coherent principle of visual information processing. In combination with the probability-statistical principle, this can serve as a basis for high reliability, plasticity, and polyfunctional character of neuronal mechanisms of the visual analysis.


[Cerebral circulatory autoregulation in the presence of orthostatic stimuli].

Autoregulation of cerebral blood flow (ACBF) under orthostatic tests (OT) was estimated in acute experiments on rabbits and cats under local anesthesia according to changes of perfusion pressure (PP) in carotid arteries, cerebral blood flow, pressure in the venous system of the brain, and resistance of cerebral vessels. OT was modeled by turning a special table with animal fixed stop of it from horizontal position to head up or down position for 40--80 degrees. In most experiments ACBF correlated with the changes of PP. Different variations of ACBF and its possible mechanisms are discussed.


[Sensitivity of a small artery of the muscular type to blood flow velocity: self-adjustment reaction of the artery's lumen].

The external diameter of the artery predominantly supplying the gracilis muscle was recorded by contact inductive transducer in anesthetized dogs. Blood flow from this artery was directed via an A--V shunt straight into the vein. An increase in blood flow from 4.9+/-0.7 to 45.5+/-6.6 ml/min with a latency of 11.3+/-1.3 sec evoked an increase of 12.6+/-1.3% in the diameter of this artery. Dilatation was independent of whether intravascular pressure at the recording site increased, decreased, or remained unchanged. The smooth arterial muscles seem to be able to "sense" the deformation and, as a result their arteries can automatically change their lumen in response to changes in blood flow velocity.


[Pancreatic atrophy: its effect on the plasma concentration of pancreatic polpeptide, gastrin and motilin in dogs].

One hour postprandial responses of plasma concentrations of pancreatic polypeptide, gastrin and motilin were detected in healthy dogs. Pancreatic atrophy was produced in these animals by obstructing their pancreatic juice flow. Basal hormone concentrations in four animals did not change significantly during 11 months of pancreatic atrophy. During this period the animals displayed a significant postprandial response. These preliminary results suggest that hormonal mechanisms involved in the digestive process are maintained during pancreatic atrophy.


[Afferent cortico-cortical connections of the orbito-frontal cortex].

Relations of frontal and orbital sections of the prefrontal cortex with different sections of neocortex were studied in cats by means of acute strychnine neurography. Afferent cortical connections of orbital and frontal sections did not differ much in their organization. Both sections had direct efferent cortical connections with motor, somatosensory and the rostral sections of the secondary auditory zone. Primary auditory field, visual and parietal associative cortex of suprasylvian gyrus had no direct afferent connections with orbito--frontal cortex. The cortico--cortical connections of orbito--frontal cortex with motor, somatosensory, and rostral sections of insular zone of neocortex appeared to be bilateral.


[Changes in the ultrastructure and protein fractions of the cortex of the motor and visual analyzers during conditioned reflex avoidance reactions].

In avoidance conditioning, rats developed changes in the range of electrophoretic proteins as well as subcellular reconstructions in neurons and synapses which enabled them to fulfill specific functions on the basis of genetically fixed biochemical processes and ultrastructures. This corroborates ideas of information storage in the c. n. s. on the basis of formation of certain neuronal ensembles by means of changes in neurons' synapses facilitating the conduction.


[Relationship between the minute superslow oscillations and the level of energy supply in brain tissue].

In animals, an increase in glycolysis intensity and processes of oxidative phosphorylation in the brain correlated with the steady potential shifts within the range of 0--1.0 Hz in the neocortex, dorsal hippocampus, and thalamic nuclei. The neurotropic drug ethymizol revealed two effects depending on the initial functional state of the rabbit: 2.5 mg/kg of the drug enhanced the amplitude of the minute waves in the frontal neocortex and dorsal hippocampus, increasing the metabolic rate in the unsteady period of conditioning, whereas after the fast conditioning the drug rendered background values to the minute oscillations and elongated the extinction of conditioned reflexes. The ethymizol appears to be an unspecific connector.


[Monoamine oxidase activity and noradrenaline concentration in tissue from symmetrical areas of cerebral cortex].

Tissue of the human brain cortex was obtained for investigations in neurosurgical operations and in autopsy. Homogenates of the tissue of symmetrical visual, auditory and skin areas were similar in the monoamine oxidase activity and adrenalin content whereas homogenates of the motor cortex tissue differed from each other in these parameters. Samples of tissue of the written language center were asymmetrical in their monoamine oxidase activity.


[Several details of the ultrastructural organization of the blood-brain barrier in humans and animals].

Electron microscope study of capillaries, arterioles, and venules of the cerebral cortex, strio--pallidar and nonneurosecretory complexes of hypothalamus of the man, cat, and rat revealed some details of the structure of the basal membrane and its interrelationship with adjacent astrocyte processes. Specific tight--junction type was present constantly among the adjacent membranes of glial cells. The system of the specializations and basal membrane seems to exert regulatory influence upon functioning of the blood--brain barrier.


[Morphometric and cytochemical parameters of skeletal muscle during long-term physical exertion].

Daily swimming for 40 days increased weight of the fast (gastrocnemius) and slow (soleus) muscles in white rats and altered the size of plane section and the relative amount of different fibers in the muscles. The slow muscle developed an anaerobic spectrum of lactatdehydrogenase isoenzymes characteristic of an intact fast muscle, whereas the fast muscle intensified its specific "muscular" spectrum of isoenzymes. By the 40th day the parameters under study tended to normalize.


[Skeletal muscle motor unit activity in cats during cold tremors].

The electrical activity of single motor units of the cat m. sartorious during the preshivering tone and shivering tremor revealed a steady frequency 5--10/sec. The transition from preshivering tone to shivering tremor involved recruitment of motor units with similar properties: the low--threshold units. The response of motor units to local thermal stimuli applied to vascular thermoreceptors depended on the level of peripheral temperature.


[Nature of vagotomy and atropine hypercoagulation].

Bilateral vagotomy and i. v. administration of atropin entailed shortening of total and thrombin time and lowering of fybrinolysis. The vagotomy brought about the changes within 3--15 min, whereas the atropinization evoked them in about 30--60 min. The maximum shortening of total and thrombin time and lowering of fibrinolysis occurred at the moment of highest activity of the cervical sympathetic system. Thereupon these effects in the blood coagulating system seem to be called forth by activity of the sympathetic system after vagotomy.


[Dynamics of peripheral nerve procoagulant and fibrinolytic activity upon electrical stimulation].

The amount of procoagulative and fibrinolytic agents in cellular organoids was studied in the cat n. ischiadicus. All cellular fractions revealed high thromboplastic activity. Plasminogen, its activator, and proactivator were discovered in the ischiadic nerve. In dogs, the changes of functional state of nerves were accompanied by discharging of tissue thromboplastin and stimulators of fibrinolysis into the external medium with stimulaneous changes of intracellular contents of hemocoagulating factors. Thus, electric stimulation of the nerve intensified its thromboplastic activity, increased concentration of analogs of the plasma factors (II, VII, IX) and stimulation of fibrinolytic agents. The data obtained suggest presence of close enough interaction between the changes of functional condition of cells and dynamics of their procoagulative and fibrinolytic power.


[Participation of the small intestine in intermediary lipid metabolism].

Data obtained in preliminarily operated healthy animals with the aid of a single or repeated lipid load achieved by means of heptadecan acid, showed that the C17:0 acid becomes involved in processes of lipid synthesis in the intestine epithelium, absorbed in the gastro-intestinal tract, and spread by the blood over different tissues, including the isolated loop of small intestine, in the form of various complex lipids. The small intestine appears to be a depot of lipids accumulating products which can be reabsorbed from the intestine lumen. As the depot reguires no hormonal or enzymatic mechanisms for mobilizing the resources, it has its advantages and is rather mobile. The "depots" ready for reabsorption of lipids in the intestine lumen appear to be one of the mechanisms for maintenance of homeostasis of nutritional substances within the organism.


[Nonsynaptic effect of the ECoG of the intact hemisphere on the impulse activity of neuronally isolated cortex].

In immobilized cats with neuronally-isolated cortex the nonsynaptic influence of the ECoG from the visual area of intact hemisphere upon unit activity of the visual and Clare-Bishop areas of the neuronally-isolated cortex was studied in the dark and during diffuse flash stimulation. Tonic unit reactions in the dark and tonic and phasic unit reactions to diffuse flash stimulation occurred in the visual and Clare-Bishop areas of the neuronally-isolated cortex. The possible nonsynaptic ECoG influence of the intact hemisphere on the activation of the neuronally-isolated cortical units is discussed.


[Effect of hyperoxia on oxygen tension in the blood and brain tissue].

Changes of the oxygen tension in the surface layers of cerebral cortex (PtO2) and arterial blood (PaO2) in the conditions of hyperoxia occurred in anesthetized rabbits: raising of O2 partial pressure in altitude chamber to 1.0 and 2.0 kgs/cm2 increased PaO2 from 76.5 +/- 11.4 mm Hg to 472.3 +/- 63.1 and 1138.0 +/- 79.4 mm Hg respectively. Raising of O2 partial pressure in altitude chamber from 0.2 to 6.0 kgs/cm2 increased PtO2 from 34.9 +/- 12.0 to 1087.5 +/- 149.8 mm Hg. Obvious defence reactions of the organism developed at the moment of transition from air breathing to pure oxygen breathing under the pressure of 1.0 kgs/cm2. High effectiveness of these reactions preserved with the raising of pressure to 3.0 kgs/cm2 and weakened with the further raising of pressure to 4.0-6.0 kgs/cm2. With prolongation of exposure to the 2.0-3.0 kgs/cm2 pressure the defence reactions slackened as well.


[Dopamine concentration in the nigrostriatal system during electrical stimulation of the head of the caudate nucleus].

The high-frequency (50/sec) stimulation of the caudate nucleus head increases the level of dophamine in the area under stimulation with simultaneous drop of dophamine content in the rest of the nucleus. The dophamine content, however, does not change in the black substance or in the putamen. The 2/sec stimulation has no effect upon the dophamine content in the area under stimulation or in the black substance but increases its level in the rest of the caudate nucleus with simultaneous decrease of the dophamine in the putamen.


[Interrelationship between the phenomena of divergence and convergence in the reflex activity of the spinal cord].

In acute experiments on cats, a single electrical stimulus applied to the afferent fibers of the sacral nerve elicits electrical responses of the efferent fibers of this nerve, as well as of other ones, i.e. pelvic and sympathetic trunks in the lumbosacral region (divergence); and the efferent fibers of the sacral nerve respond to stimulation not only through its afferent fibers but also in the said nerve trunks (convergence). A similar pattern occurs during separate electrical stimulation of the pelvic nerve and sympathetic trunk, and of L4 to S3 dorsal roots, with monitoring electrical responses of the corresponding nerves and ventral roots. A close relationship between the divergence and convergence seems to exist.


[Blood flow in skeletal muscle microvessels in normoxia and arterial hypoxemia (microcinematographic studies)].

Vital microfilming revealed peculiarities of blood flow in microvessels of 2-5-micron diameter under relatively resting conditions, in normoxia, as well as the microcirculatory response to hypoxia (breathing with mixture of nitrogen and 6-8% oxygen for 5 min), in intact temporal muscle of rat. The average blood flow velocity in normoxia was 1.14 +/- 0.04 mm/sec in capillaries and 2.43 +/- 0.08 mm/sec in terminal arterioles. Breathing with the hypoxic mixture decelerated blood flow in 75% of the vessels. The blood low velocity in the muscle capillaries correlated with arterial blood pressure.


[Analysis of focal potentials in the cat cerebral cortex during activation of cerebello-thalamo-cortical projection systems].

Peculiarities of topographical distribution of responses of the cat cerebral cortex to stimulation of cerebellar and thalamic (ventro-lateral and ventral anterior) nuclei as well as cerebello-thalamo-cortical projection system and comparison between the cerebellar and thalamic responses revealed differences in focal potentials evoked in pericruciate and parietal cortex. The latencies of the potentials, similarity in shape and in depth of reversion suggest that the cerebello-cortical responses in the pericruciate cortex are mediated through the thalamic ventro-lateral nucleus making synapses in III-IV cortical layers while responses in the parietal cortex--through the thalamic ventral anterior nucleus making synapses in more superficial layers.