Effects of glucose and chromium(III) concentrations in the medium on the uptake of 51Cr by brewer's yeast. The incorporation of trivalent chromium into S. carlsbergensis as function of time, the effects of chromium and glucose concentrations in the medium on the uptake of 51Cr by the yeast cells, and the effect of chromium on growth of the yeast were studied. 51Cr was taken up by yeast cells most rapidly during the logarithmic growth period in Sabouraud's liquid medium containing 5% glucose. Cells grown in a medium containing only 0.5% glucose at the beginning of cultivation incorporated very little 51Cr, and incorporation ceased when the glucose concentration was reduced to less than 0.1%. Addition of 5% glucose into this culture resulted in a very rapid increase in the 51Cr uptake. The second glucose addition did not notably increase the rate of 51Cr uptake by the yeast. Chromium, reduced yeast growth slightly, however, was not clearly toxic.


Potentiating action of 5-fluorouracil when used in combination with platinium compounds and cyclophosphamide in treatment of advanced L1210 leukemia. Nine new organoplatinum (Pt) compounds, cyclophosphamide (CY), and 5-fluorouracil (FU) were used singly and in combination in treatment of advanced L1210 leukemia in C57BL/6 X DBA/2 hybrid mice. In each experiment the Pt + CY dual combination was minimally supra-additive at the doses chosen. However, eight of the nine Pt + CY + FU combination regimens enhanced markedly the increased life span of treated mice as compared with the corresponding dual Pt + CY combination. Collectively, the cure rate (greater than 60-day survival) was less than 6% with the various Pt + CY combinations, and was increased to over 63% upon inclusion of FU in the regimens.


Electronic properties of sulfhydryl- and imidazole-containing peptide-cobalt(II) complexes: their relationship to cobalt(II)-substituted "blue" copper proteins. The electronic properties of 2:1 sulfhydryl- and imidazole-containing peptide-Co(II) complexes have been investigated and compared with those of Co(II)-substituted "blue" copper proteins. The Co(II) complexes of N-mercaptoacetyl-L-histidine and 3-mercaptopropionyl-L-histidine gave the ligand field parameters of deltat = 4110 and B = 756 cm(-1), and of deltat = 4120 and B = 724 cm(-1), respectively. These values correspond well to those (deltat = 4900 and B = 730 cm(-1)) of Co(II)-substituted "blue" copper proteins. The energy differences between S leads to M(II) charge transfer bands of Co(II)-Cu(II) couples were about 14,000 cm(-1) in both the proteins and the model complexes. The spectral results suggest that "blue" copper site has a pseudotetrahedral geometry and a deep absorption near 600 nm atributes to S leads to Cu(II) charge transfer.


Carbon-13 and proton nuclear magnetic resonance spectroscopy of water-soluble porphyrins and metalloporphyrins. Carbon-13 and proton nuclear magnetic resonance (NMR) spectra have been recorded for porphyrins, zinc porphyrins, and iron(III) porphyrin complexes in aqueous media. Spectra of porphyrin-c and hemin-c confirm the structure with thioether linkages at positions alpha to the porphyrin ring. The pattern of NMR isotropic shifts has implications regarding electron transfer in cytochrome-c. Free-base porphyrin-c and meso-substituted porphyrins have been examined for pyrrole nitrogen-hydrogen tautomerism and possible aggregation in aqueous solution. Zinc porphyrin 13C NMR spectra were recorded in order to provide diamagnetic references for paramagnetic iron(III) derivatives. Low-spin iron(III) porphyrin-biscyano complexes in aqueous solution exhibit NMR isotropic shift patterns similar to those previously observed for related compounds in non-aqueous media. The first 13C NMR spectra are reported for mu-oxo-bridged iron(III) porphyrin dimers. A partially resolved spectrum of a high-spin iron(III) porphyrin has also been obtained. Patterns of 13C and proton isotropic shifts are compared, and unpaired spin delocalization mechanisms for 13C resonances are discussed in a qualitative manner.


Electric hysteresis and mitochondrial incorporation of RNAs from different sources. The paper reports the characteristics of four different RNAs from yeast, Torula and calf thymus of molecular weight ranging between 15,000 and 30,000. The gel-filtration behaviour with aqueous and partially qqueous solvents is studied together with the response of the four RNAs to static electric fields of strength ranging between 20 and 35 kV/cm. The relationship between molecular weight and extent of electric hysteresis is linear for all RNAs, while tRNA slightly deviates from such a relationship. The ability of the RNAs to permeate biological mebranes or bind membrane components such as lecithins is studied with rat liver mitochondria and a two-phase system with egg lecithin dissolved in the organic phase and RNA in the aqueous one. There is no apparent relationship between molecular weight of the RNAs and their ability to interact with biological membranes.


Hormone responsiveness of adenylate cyclase activity of cultured myogenic cells. We studied the effect of catecholamines on the adenylate cyclase activity of myogenic cells of the L6 line during the differentiation process. The enzyme of mononucleated myoblasts was found to be activated by adrenaline L, noradrenaline L, and to a small extent, by adrenaline D and dihydrocymandelic acid. The adenylate cyclase of the differentiated cells responded to adrenaline L and noradrenaline L but not to adrenaline D or dihydroxymandelic acid. This activation could be inhibited by the addition of DOPA and propranolol, a specific beta adrenergic blocker. alpha adrenergic compounds such as phentolamine did not have any effect. It is concluded that beta adrenergic receptors are present on myogenic cells before and after differentiation.


Solubilization of Spiroplasma citri cell membrane proteins with the anionic detergent sodium lauroyl-sarcosinate (Sarkosyl). 1. Up to 90 per cent of the membrane proteins from Spiroplasma citri could be solubilized with the anionic detergent Sarkosyl (sodium lauroyl-sarcosinate). Maximal solubilization was obtained with 6 to 20 mumoles of of detergent per mg of membrane protein. The insoluble residue, comprising about 10 per cent of the membrane protein, contained mainly the protein spiralin, which is quantitatively the major one of this membrane. 2. Mg2+ ions completely prevented solubilization of the membrane proteins at a molar ratio of MgCl2/Sarkosyl greater than 0.5. 3. The selectivity of Sarkosyl was also tested at low detergent concentrations and in the presence of Mg2+ ions. Spiralin was the least soluble protein also under these conditions. Other proteins were not selectively solubilized. 4. An electrophoretical and immunoelectrophoretical approach was used to study the interaction between Sarkosyl and membrane proteins. The results indicated that Sarkosyl should be considered as a mild detergent which usually solubilizes membrane proteins without gross donformational changes. This hypothesis was supported by experiments with a membrane-bound enzyme in the presence of Sarkosyl.


[Isolation of myosin light chain from porcine heart by preparative electrophoresis and study of the polypeptides obtained by cyanogen bromide action]. A simple, rapid and efficient procedure is developed to isolate proteins with identical or different isoelectric points such as pig cardiac myosin light chains. Preparative electrophoresis on discontinuous polyacrylamide slab gels in the presence of urea allows a very good separation of each light chain (L27 and L18) and heavy chain from highly purified myosin. An original elution procedure of the proteins fixed and localized by amido schwartz allows the isolation of the L27 and L18 light chains in quantities sufficient to carry out structural studies. Homogeneity of light chains thus isolated is checked by the analysis of cyanogen bromide peptides. Structural similarities can be demonstrated between myosin light chains of beef and pig heart.


[Immobilization of coenzyme A on a hydrosoluble polymer]. Our purpose being to work out a "continuous flow" enzymatic reactor of acetylation with a cofactor, we present here some results about the immobilization of coenzyme A on T40 dextran. Two methods of fixation are compared with regard to the capacity and the biological activity of the polymers thus obtained.


A comparison of the mechanisms and some properties of instructed sudomotor and cardiac control. Instructed control defined as differential compliance with verbal instructions to increase and decrease a response was assessed when a change in sudomotor activation or heart rate was specified as the behavioral goal. Instructed control of heart rate was evident prior to explicit feedback training for this response, but instructed control of sudomotor activation defined as finger sweating and measured as skin conductance was not. Feedback training subsequently established instructed control of sudomotor responding, but such training did not lead to a significant improvement in control of heart rate. Explicit strategy suggestions emphasizing emotional responding and intended or actual movement appeared to interfere with the performance of instructed control under both target conditions. Instructed changes in heart rate were attended by correlated changes in somatomotor and respiratory function. Somatomotor and respiratory responses were also observed when subjects were instructed to change sudomotor activation, but these correlated activities were of small magnitude and were not augmented by feedback training as was target responding. Several accounts of the basis for differences that were evident between the target conditions with respect to feedback effects and response patterns are discussed.


Methodological issues in alpha biofeedback training. Current controversies concerning outcomes of EEG alpha feedback training are at least in part due to methodological differences among different studies. The aim of this paper is to provide future and present researchers in this field with an analysis of methods used in most of the studies published from 1968 to 1976, and to comment on those methodological issues we think most important. These include alpha assessment, training schedules, and uni- versus bidirectional training. This analysis is accomplished in part by a series of tables listing 45 studies and the detailed methodologies used. It is believed that the probabilities of successful feedback enhancement of alpha can be substantially improved by incorporating the following suggestions: (a) employing at least four training sessions, (b) the use of continuous rather than dichotomous feedback, supplemented by periodic quantitative scores of progress, and (c) using training trials of at least 10 minutes' duration.


Effects of pharmacologic agents on umbilical blood flow in fetal lambs in utero. We studied the effects of pharmacologic agents on umbilical blood flow and umbilical-placental vascular resistance in 18 fetal lambs in utero. Three groups of drugs were identified: the first had no effect on umbilical blood flow or umbilical-placental vascular resistance; the second altered umbilical blood flow secondary to changes in heart rate and placental perfusion pressure, but did not change umbilical-placental vascular resistance; the third decreased umbilical blood flow and increased umbilical-placental vascular resistance. The studies suggest mechanisms by which umbilical blood flow is regulated in the fetal lamb.


Intrauterine growth in Hong Kong Chinese. The recorded data on birth weight and gestational age of 16,836 babies born at Tsan Yuk Hospital in Hong Kong for the years 1970 to 1972 was analysed by computer. The means, standard deviations, and percentiles were separately obtained for nine sub-groups between 28 and 42 weeks and they were compared with similar series from Taiwan, Singapore, America and England. Chinese babies in Hong Kong were significantly heavier compared to most series between 32 and 35 weeks (p less than or equal to 0.001), and consistently lighter compared to all series studied between 38 and 42 weeks (p less than or equal to 0.001). Reasons for these findings are discussed.


The postnatal development of rats born preterm and postterm. II. Liver, brain, heart and kidneys. Groups of 3 preterm (duration of gestation 22 days), 3 term (23 days), and 3 postterm (24 days) rats have been fed together by 1 mother rat. The postnatal growth of liver, brain, heart and kidney has been studied up to the 30th day of life. The postnatal loss of water shows good correlation with the maturation of each organ. The postnatal loss of water is marked in brain and kidneys, but only slight in liver and heart. The pronounced growth spurt of the brain at the about 10th day of life is probably due to the opening of the eyes. The growth spurt of the liver at the 15th day may be due to the supplementary food at the time of weaning. The effect of intrauterine undernutrition in postterm rats is most strikingly demonstrated in the liver. Postnatal undernutrition in preterm rats causes a retardation of growth of the liver and kidneys.


Quantification of intrauterine malnutrition. Small-for-gestational-age infants are a heterogeneous collection of growth-retarded infants. In the subgroup of intrauterine-malnourished infants an attempt is made to quantify the degree of malnutrition by postnatal measurements of length, weight and fat-fold thickness. In 48 clinically wasted and not-wasted term newborns, regardless of birth weight, the ponderal index of Rohrer (100 X W/L3) was determined and the deviation from 'normal' calculated. The deviations are correlated with fat-fold thickness and clinical diagnosis. A highly significant correlation gives support to the view that both ponderal index deviation from 'normal' and fat-fold thickness are useful parameters to quantify the effect of intrauterine malnutrition in newborns.


Postnatal changes in blood S-adenosylmethionine concentration. Some observations in hyaline membrane disease. The blood concentration of S-adenosylmethionine in 18 premature neonates affected by hyaline membrane disease did not differ from that found in a control group of healthy premature newborns. However, these values are higher than those found in full-term infants: this fact suggests that the methionine cycle is active in both the fetus and premature neonate with consequent conservation of homocysteine sulfur. These data provide ancillary evidence in support of the hypothesis that in premature babies cyst(e)ine is an essential amino acid. The concentration of S-adenosylmethionine reaches its lowest level 30 days after birth and then stabilizes at the age of 2--5 months with blood levels similar to those of the normal adult.


The effects of aflatoxin B1 on rat fetal lung lipids. The administration of aflatoxin B1 to rats on days 17 and 19 of pregnancy caused increased synthesis of the total lipids and the fatty acids, and decreased synthesis of the phosphatidyl choline in 21-day-old fetal lung. Aflatoxin B1 caused toxicity in the fetal lung as evidenced by the excessive accumulation of the lamellar bodies and the osmiophilic spheroids in the type II cells and the alveolar lumen, respectively. The rearrangement of the lamellar form to the continuous sheet-like tubular myelin form was reduced in the alveolar lumen of the treated lung.


The rabbit during the last third of gestation. Data concerning the whole fetus, its diaphragm and brown adipose tissue. Total lipid, protein and glycogen concentrations were determined for the diaphragm and interscapular brown adipose tissue of fetal (22-31 days of gestation) and neonatal rabbits. In the diaphragm, protein concentration doubles and lipid concentration drops to half its initial value during the period under study; the glycogen level reaches its maximal value at 27 days, and decreases thereafter. In the brown fat, the lipid concentration rises steadily until the immediate prenatal period; the protein concentration remains steady and the glycogen is highest at 29 days of gestation. Fetal plasma glucose and insulin levels increase steadily; there exists a positive correlation between fetal plasma insulin levels and fetal body weight.


Relationship of intra-oesophageal pressure to mouth pressure during the measurement of thoracic gas volume in the newborn. During the measurement of thoracic gas volume, mouth pressure changes were compared to oesophageal pressure changes using an oesophageal balloon system. In individual babies the correlation was high, with r values in excess of 0.98. In other babies the correlation was less satisfactory due to cardiac contractions producing artefacts in the oesophageal pressure trace. The overall correlation obtained from analysing 155 respiratory efforts in a group of 21 babies studied on 23 occasions exceeded an r value of 0.90. We conclude that it is valid to use an oesophageal balloon system to measure changes in intrathoracic pressure.


Effect of lipid loading on fetal uptake of free fatty acids, glycerol, and beta-hydroxybutyrate. The possibility of influencing the fetal uptake of free fatty acids (FFA), beta-hydroxybutyrate (beta-OH), and glycerol was demonstrated by enhancing the maternal blood level of these substances by means of 10% intralipid infusions to the mothers during delivery. The FFA uptake, which was not significant in fetuses of control mothers, became positive in fetuses born after maternal infusion with intralipid. The uptake of beta-OH and glycerol, which were positive in normal conditions, increased in fetuses from intralipid-infused mothers. These studies demonstrate that, after intralipid infusions to the mothers, the fetal FFA uptake could be correlated with the FFA concentration difference between maternal arterial, and fetal umbilical arterial blood. Since the fetal uptake of FFA subsequent to intralipid infusions is not negligible, we consider the possibility that lipid infusions to the mothers could be an approach to the treatment of the fetus with poor intrauterine growth.


A reduction apparatus for femur fractures. The majority of femur fractures are closed fractures in the mid-third of the femoral shaft. A very well known fixation technique is the one using an intramedullary pin, which is inserted from the hip side. Open reduction of the fracture is mostly applied but the majority, between 85 and 93%, of the fractures are closed and therfore a more logical and safer technique would be closed reduction. However, this technique, also called blind-nailing, is more difficult. Besides an x-ray scanner with a monitor it also requires experience of the surgeon and some special tools to supply the necessary reduction forces to the proximal and distal parts of the femur. This publication describes a new designed reduction apparatus (1), that primarily simplifies blind-reduction of femur fractures, but can also be used for any other operation technique where a good grip on bones has to be provided with a minimum of tissue damage. The apparatus is designed to be used with standard Kirschner-wires and is easy to apply in combination with the existing operation techniques, and does not require special skill.


Dental implant fixation by electrically mediated process. I. Interfacial strength. In order to determine the effect of electrical stimulation on canine alveolar bone, porous PMMA dental implants with a solid core (on which a Pt-13% Rh electrode was wound) were implanted in the mesial socket of the canine mandibular fourth premolars bilaterally. The positive electrode was implanted into the distal socket. The power pack was placed over the masseteric fossa. The implants, wires and power packs were all implanted subcutaneously. Each animal had an experimental and control implant. Mechanical push-out samples were prepared by sectioning a 2mm thick section of the mandible with the implant in the middle. The samples were tested immediately and the load-deflection curves were obtained.


Electrochemical behavior of amino acids and their influence on the anodic oxidation of glucose in neutral media. Body fluids contain a large number of amino acids along with glucose. Therefore, the electrochemical behavior of amino acids should be considered in studying the anodic oxidation reaction of glucose for biological applications. Potential-sweep and steady-state measurements with different platinum electrodes under neutral conditions have shown that the oxidation of amino acids is basically possible. However, their presence, especially as a mixture, has a remarkable influence on the glucose oxidation and the anodic reaction is strongly inhibited. With respect to the degree of inhibition, they can be classified into two groups. The inhibiting effect is particularly drastic in the case of basic and unsaturated amino acids as well as the ones containing sulphur because of their strong absorption at the electrode surface. The glucose currents are inhibited by about 90% under steady-state. In addition to the direct electrochemical inhibition, the following bacterial decomposition of amino acids is probably also responsible for the drastic effect. However, about 10% of the glucose currents still remain measurable indicating that glucose is detectable at physiological concentrations even under extremly unfavorable conditions. This result is of basic importance in operating a biofuel cell or in measuring glucose concentrations.


Large agarose beads for extracorporeal detoxification systems. A method is reported by which agarose beads of diameter 1000 to 10000 microns can be prepared from Sepharose (R) 4B (native bead diameter 40 to 190 microns). Haemoperfusion experiments indicate that the enlarged beads are relatively haemocompatible; platelet loss is considerably less than that reported for many other bio-materials employed in haemoperfusion, and haemolysis is slight even after perfusion for several hours at flow-rates in excess of 25 ml/min. The beads can be activated by cyanogen bromide for the immobilisation of proteins. The sites for protein fixation are not restricted to the outside surface of the beads; small water soluble molecules, and serum proteins diffuse quite rapidly through the enlarged beads. A possible medical application of the large beads is in extracorporeal detoxification by chromatographic extraction or enzymatic modification, particularly of lipophilic toxins, using the enlarged beads as a carrier-matrix. The results described in this publication prove the viability of this concept. Such methods should be especially useful as artificial supports in fulminant hepatic failure.


In vivo interactions between novel filler free silicone rubber and blood. To evaluate the thrombogenicity of the novel filler free silicone rubber (FFSR) prepared in our laboratory, its interactions with blood were studied. The test samples (FFSR) along with control Silastic samples were placed in an extracorporeal shunt and primed with sterilized normal saline. The blood from an anaesthetized and systemically heparinized dog was passed over these samples for predetermined time intervals. After washing, fixing, etc., the platelets adhering to the samples were counted under light microscopy. To study the morphological changes of the platelets adhering to the samples, they were examined under scanning electron microscope. The number of platelets adhering to the FFSR samples was very small compared to the Silastic samples. For example, when the blood was passed over the samples for 10 min the number of platelets sticking per 0.14 mm2 surface area was 10 for FFSR samples compared to 380 for Silastic. Furthermore, there were no leukocytes on FFSR samples compared to 10 on Silastic. From these studies, the novel filler free silicone rubber prepared in our laboratory was judged to be more compatible with formed elements of blood compared to the Silastic material.


Post-heparin plasma lipolytic activity in acute hepatitis. Post-heparin plasma lipolytic activity (PHLA) was measured in 21 patients with acute viral hepatitis. PHLA was significantly reduced in all patients (p less than 0.0005), whose mean activity was only 32% of the control subjects. An inverse correlation (p less than 0.05) was found between PHLA values and serum triglycerides levels. During recovery, the normalization of PHLA was much slower than that of the usual tests of liver function. PHLA measurement may represent a new and sensitive test of liver function.


Circulating immune complexes in multiple sclerosis. Relation to clinical and biological parameters. Circulating immune complexes were looked for on 38 clinically definite MS (multiple sclerosis) patients compared to 35 other neurological patients and 26 healthy subjects. 29% of the MS sera and 8.6% of the other neurological sera were positive, whereas none of the control sera were positive. These differences are significant. Clinical status was analysed as regards the age at onset, the duration and course of the disease, the disability of the patients and the treatment they received. CSF (cerebrospinal fluid) parameters studied were pleocytosis, concentration of total protein, electrophoresis. The results suggest that IC (immune complex) are more frequent during the first 10 years of the MS disease, in patients with blood-brain barrier damage and in patients without oligoclonal IgG.


Effect of gastric intubation of the gastric loss of serum albumin. In a group of 18 inpatients, the catabolism of serum albumin rate, in percentage of intravascular albumin pool, was measured during two successive periods of 7 days. In the first experimental period, we did no intubation, while during the second, a tube was kept in the stomach, with an overnight intragastric perfusion of an isotonic solution of sodium bicarbonate. With the same batches of labelled albumin, we measured the serum albumin catabolism, in a similar way, in a group of 19 normal subjects, for two weeks, without gastric intubation. The difference in the rate of serum albumin catabolism, during the first and second period, is positive and amounts to +0.547 percent +/- 0.214 (mean +/- SEM) in the intubated group, and +0.765 percent +/- 0.207 in the control group. The weaker decrease in catabolism rate during the second period in the intubated group, as compared to the control group, is not statistically significant (t = 0.731). We conclude that continuous intubation of the stomach for 7 days does not increase the catabolism rate of serum albumin. Therefore, it should not significantly increase the loss of albumin in the gastric lumen.


Use of laser-nephelometer to quantitate lipoprotein-bound immunoglobulins in human sera. Importance of the diluting reagent. If the method using Hyland LAS-RTM kit reagent recommended by the manufactorer yielded excellent results to measure immunoglobulins free in serum, the same is not true when one quantitates immunoglobulins bound with antigens, especially with lipidic antigens. Since the specificity of Hyland antisera is not the cause of this difference, we have studied therefore the effect of the diluting buffer on the antisera, on the blank, and its consequences on the assay. The abnormalities encountered in the results were due to precipitation of lipoproteins and immune complexes by the diluting buffer yielded in the kit. We avoided entirely these errors by preparing a blank, not in NaCl 0.15 M, but in the kit reagent used to dilute the antisera.


The fate of clofibrate in the perfused rat liver. Rat liver perfusions were carried out with [methyl 14C]-labelled chlorophenoxyisobutyrate (CPIB) in the perfusate. In three hours, livers passed 42% of the CPIB into the bile (40% of which was conjugated), oxidized 0.3% to CO2 and retained 2.2% within the liver tissue. The fate of CPID in perfused livers from rats pretreated with clofibrate for one week was similar. Subfractionation of the liver showed that most of the retained radioactivity was located in the cytosol. The substantial uptake and transport of the drug through the tissue show that its effects on liver metabolism could be due to direct action.


Preliminary results of the combination methotrexate-asparaginase in patients with acute non lymphoid leukemia. Twenty-three refractory and/or relapsing acute non-lymphoid leukemia patients were treated with a combination of methotrexate (MTX) and asparaginase (Aase) slightly modifed from that recently proposed by Capizzi et al. Patients received MTX on day 1, followed by Aase 24 hours later; the two day course was repeated weekly. The starting dose of MTX was 60 mg/m2 and was increased by 50% at each course to maximum toxicity. The dose of Aase was kept constant at 10,000 u/m2. Twelve patients achieved complete remission lasting 3 to 58 weeks, with 8 patients surviving more than 30 weeks. Toxicity has been remarkably mild with the major problem being hypersensitivity to Aase.


Biochemical problems caused by some cryoglobulins. An unsuspected cryoglobulinaemia may be responsible for incorrect serum protein results and thus cause dysglobulinaemia to remain undetected. When cryoglobulins precipitate above laboratory temperature, they will be removed with the clot during centrifugation of the blood sample if they have not previously been suspected clinically or biologically. In the case of massive cryoglobulinaemia, one might find normal protein results but such results are incorrect and if only total protein estimation has been requested, dysglobulinaemia can remain undetected. However, if electrophoresis can also been carried out, a slight abnormality of the gamma globulin fraction might be observed and this ought to incite one to look for cryoglobulin by the usual method (i.e. at 37 degrees C), even in the absence of clinical evidence.


Colony-forming units in the spleen and bone marrow of young (C57BL/6xDBA/2)F1 hybrid mice. Spleen or bone marrow cells from (C57BL/6 X DBA/2)F1 hybrid mice ranging in age from 1 to 32 days were transplanted into syngeneic irradiated adult recipients. By enumeration of macroscopic hemopoietic spleen colonies 8 days after transplantation, the colony-forming unit(CFU) content of the spleen and bone marrow of the young donor mice was determined. The CFU concentration in the bone marrow, initially at a level of 15.1--17.0 CFU/105 nucleated cells, increased during the third week of life and reached a value comparable to that of the adult during week 4. In contrast, the CFU concentration of the spleen decreased during the first 2 weeks and reached a plateau at a level of 4.45--6.66 CFU/105 nucleated cells during the third and fourth weeks of age. This was still significantly higher than that of the adult hybrid. The rise in prominence of the bone marrow as a hemopoietic organ during this period appeared to be due to an increase in total cellularity coupled with an increase in CFU concentration in this hybrid. While the cellularity of the spleen also increased during this time, the CFU concentration decreased, resulting in little change in the total CFU content of this organ.


High renal plasma flow lability in the kidneys of hypertensive patients. The spontaneous changes in renal plasma flow (RPF) were determined by sodium paraamino hippurate clearance (CPAH) in the individual kidneys of 71 patients with essential and secondary hypertension. These changes were expressed as changes in CPAH and as changes in CPAH per 100 ml Glomerular Filtration Rate (GFR = inulin clearance) for every individual kidney. Sixteen normal subjects were used as control. The RPF changes were measured between two consecutive 10 minute clearance periods during separated kidney function tests. In all the hypertensive groups studied, when RPF variability was expressed per 100 ml GFR, the variability was found to be two to five times greater than in normals. This findings suggests that in the hypertensive state the blood flow changes in the kidney are more labile than in normals. The high lability of renal blood flow could reflect and abnormality in renal vascular tone. This abnormality could be an important factor in the pathogenesis and maintenance of high blood pressure.


Starvation and sucrose activity in small intestinal mucosa. An evaluation of different tissue preparations and reference systems. Starvation for 48 hrs reduced the activity of sucrase referred to unit length in rat proximal small intestine by approximately 30%, irrespective of whe her mucosal scrapings, isolated villus epithelial cells or brush border membranes were investigated. Sucrase activity referred to unit weight, unit protein or to unit DNA of intestinal epithelium did not change.


Prenatal diagnosis of galactosemia.

Prenatal diagnosis of galactosemia. We have monitored 3 pregnancies at risk for galactosemia by deficiency in Galactose-1-Phospho uridyl transferase. Galactosemia was diagnosed in the 1st case; heterozygoty in the 2nd, and a "double heterozygoty" in the 3rd. The latter is the first example of such a diagnosis. Post natal confirmation was obtained in the three cases. Arguments are given for the usefulness of this prenatal diagnosis.


Sialic acid-containing glycoconjugates in human lactation urine. The excretion rate of neutral hexoses, fucose and sialic acid of oligosaccharide and glycopeptide fraction has been determined in lactation urine. Thin layer chromatography has been used to investigate the excretion pattern of oligosaccharides, specially sialyl-oligosaccharides, during the course of lactation and after weaning. Lactation urine contains sialyloligosaccharides which are not present in normal urine and their presence has been studied up to the 3rd week after weaning. These results indicate a mammary origin for most of these compounds and confirm the hypothesis of previous research.


Lecithin bilayers. Density measurement and molecular interactions. Density measurement are reported for bilayer dispersions of a series of saturated lecithins. For chain lengths with, respectively, 14, 15, 16, 17, and 18 carbons per chain, the values for the volume changes at the main transition are 0.027, 0.031, 0.037, 0.040 and 0.045 ml/g. The main transition temperature extrapolates with increasing chain length to the melting temperature of polyethylene. Volume changes at the lower transition are an order of magnitude smaller than the main transition. Single phase thermal expansion coefficients are also reported. The combination of X-ray data and density data indicated that the volume changes are predominantly due to the hydrocarbon chains, thus enabling the volume vCH2 of the methylene groups to be computed as a function of temperature. From this and knowledge of intermolecular interactions in hydrocarbon chains, the change in the interchain van der Waals energy, delta UvdW, at the main transition is computed for the lecithins and also for the alkanes and polyethylene at the melting transition. Using the experimental enthalpies of transition and delta UvdW, the energy equation is consistently balanced for all three systems. This yields estimates of the change in the number of gauche rotamers in the lecithins at the main transition. The consistency of these calculations supports the conclusion that the most important molecular energies for the main transition in lecithin bilayers are the hydrocarbon chain interactions and the rotational isomeric energies, and the conclusion that the main phase transition is analogous to the melting transition in the alkanes from the hexagonal phase to the liquid phase, but with some modifications.


The equation of motion for sperm flagella. The equation of motion for sperm flagella, in which the elastic bending moment and the active contractile moment are balanced by the moment from the viscous resistance of the surrounding fluid, is solved for a wave solution that superimposes partial solutions. Substitution of the expression for the wave solution into the equation leads to an expression for the active contractile moment. This active moment can be decomposed into two parts. The first part describes an active moment that travels over the flagellum with the mechanical flagellar wave, the second part represents a moment in phase over the entire length of the flagellum, which decreases linearly towards the distal tip. The linear synchronous moment, to which an amount of traveling moment has been added as a perturbation, leads to wave solutions that closely resemble flagellar waves. Properties such as wavelength and wave amplitudes and also the shape of the waves in sea urchin sperm flagella at different frequencies are accurately described by the theory. The change in wave shape in sea urchin sperm flagella at raised viscosity is predicted well by the theory. The different wave properties caused in bull sperm flagella by different boundary conditions at the proximal junction are explained. When only a traveling active moment is present in a flagellum, the wave solutions describe waves of a small wave length in a long flagellum. Some properties of the wave motion of sperm flagella are derived from the theory and verified experimentally.


Interaction between batrachotoxin and yohimbine. The neurotoxins, batrachotoxin and veratridine, are specific activators of sodium channels and cause an increase in the rate of 22Na uptake in neuroblastoma cells. Yohimbine, an indolakylamine alkaloid, inhibits this batrachotoxin-induced 22Na uptake. The dose-response curve of yohimbine suggest that the inhibitor acts reversibly on a single class of binding sites with dissociation constant of 3--4 x 10(-5) M. The dissociation constant is not affected by depolarization from--41 to 0 mV. Kinetic and equilibrium experiments indicate that yohimbine is a competitive inhibitor of the action of batrachotoxin. These results support the conclusion that yohimbine inhibitis the sodium flux by acting on the channel gating mechanism rather than by occluding the channels.


The dynamics of the ventricular wall and some observations on blood flow. An expression for the energy of motion of the wall of the left ventricle is developed. A cylinderical model is assumed for the left ventricle, and symmetry is used to produce the problem to a two-dimensional problem. Result obtained indicate that consideration of the energy of motion can be useful in problems of clinical diagnosis. Some correlation between previously published experimental results is also made with the equations derived in this paper.


Postreplication repair in mammalian cells after ultraviolet irradiation: a model. A model is presented for bypass of ultraviolet-induced damage in DNA during replication. The overall process is initiated by the introduction of a single-strand break into parental DNA near the point of arrest of synthesis, followed by a transient crossing-over step similar to that envisaged in genetic recombination. The mechanism proposed provides an alternative explanation to existing models and is entirely consistent with available data on postreplication repair in mammalian cells. In addition the model explains the low level of recombination repair observed in mammalian cells.


A mathematical model for spreading cortical depression. A mathematical model is derived from physiological considerations for slow potential waves (called spreading depression) in cortical neuronal structures.  The variables taken into account are the intra- and extracellular concentrations of Na+, Cl-, K+, and Ca++, together with excitatory and inhibitor transmitter substances. The general model includes conductance changes for these various ions, which may occur at nonsynaptic and synaptic membrane together with active transport mechanisms (pumps). A detailed consideration of only the conductance changes due to transmitter release leads to a system of nonlinear diffusion equations coupled  with a system or ordinary differential equations. We obtain numerical solutions of a set of simplified model equations involving only K+ and Ca++ concentrations. The solutions agree qualitatively with experimentally obtained time-courses of these two ionic concentrations during spreading depression. The numerical solutions exhibit the observed phenomena of solitary waves and annihilation of colliding waves.


An analysis of the electrical properties of a skeletal muscle fiber containing a helicoidal T system. The linear electrical properties of skeletal muscle fibers have been analyzed using lumped circuit analogues of helicoidal T system. The geometry of a helicoid is assumed to produce two electrical effects, modeled separately. One model is motivated by the pitch or tilt of the T system, which forces the current flowing in the lumen of the tubules to have a longitudinal projection. The second model is motivated by the longitudinal continuity of a helicoid, which forms a structure similar to a cable within the fiber. The pitch or tilting of the T system plane modified the longitudinal resistance of the fiber, making it slightly frequency dependent; however, the magnitude of the change was less than 0.1%. The longitudinal connections between T system networks had a more complicated effect; the magnitude of the correction was again less than 0.1%. The conclusion from this analysis is that a helicoidal T system, whose pitch is constrained by the sarcomere spacing, will not affect electrical signals recorded intracellularly in intact fibers.


Local anesthetic block of sodium channels in normal and pronase-treated squid giant axons. The inhibition of sodium currents by local anesthetics and other blocking compounds was studied in perfused, voltage-clamped segments of squid giant axon. When applied internally, each of the eight compounds studied results in accumulating "use-depnedent" block of sodium currents upon repetitive pulsing. Recovery from block occurs over a time scale of many seconds. In axons treated with pronase to completely eliminate sodium inactivation, six of the compounds induce a time- and voltage-dependent decline of sodium currents after activation during a maintained depolarization. Four of the time-dependent blocking compounds--procaine, 9-aminoacridine, N-methylstrychnine, and QX572--also induce altered sodium tail currents by hindering closure of the activation gating mechanism. Treatment of the axon with pronase abolishes use-dependent block completely by QX222, QX314, 9-aminoacridine, and N-methylstrychnine, but only partially be tetracaine and etidocaine. Two pulse experiments reveal that recovery from block by 9-aminoacridine or N-methyl-strychnine is greatly accelerated after pronase treatment. Pronase treatment abolishes both use-dependent and voltage-dependent block by QX222 and QX314. These results provide support for a direct role  of the inactivation gating mechanism in producing the long-lasting use-dependent inhibition brought about by local anesthetic compounds.


Mean activity coefficients for the simple electrolyte in aqueous mixtures of polyelectrolyte and simple electrolyte. V. Common counterion mixtures of alkali-metal dextransulfates with alkali metal chlorides. Mean molal activity coefficients of simple electrolyte in aqueous solutions of Li, Na, K or Cs salts of dextransulfate (DS) with added LiCl, NaCl, KCl or CsCl are reported. The measurements were carried out by means of an electrochemical cell method using a cation exchange membrane as cation selective electrode and Ag/AgCl electrodes. For LiDS-LiCl, NaDS-NaCl and CsDS-CsCl systems the polymer concentration, mp, was varied from 0.0088 to 0.113 m and at a given mp the ratio X of the polymer to salt concentration was varied from 0.5 to 16. Due to the insolubility of KDS in high concentration of KCl, the measurements on KDS-KCl system were performed in the mp range of 0.0088--0.089 m and some of the smaller X values were omitted. The activity coefficient results are compared to Manning's limiting laws, the additivity rule, and to new limiting laws. The additivity rule can give an excellent representation of the data for all mp values when gammap is used as an adjustable parameter.


Electro-optical studies on synthetic polyelectrolytes. IV. Electric polarizability and conformation of poly-N-methyl-2-vinylpyridinium bromide in aqueous solution. Measurements of the relaxation time on aqueous solutions of the title polyelectrolyte as a function of the concentration and of the molecular weight show that its conformation at very high dilution can be better accounted for by a weakly bending rod or wormlike chain model, with persistence length ranging from 200 to 400 A. The analysis of the field strength dependence of the electric birefringence yields electric polarizability values which increase sharply with the dilution and are not significantly dependent upon the molecular weight. This has been tentatively interpreted on the basis of the theories derived by Oosawa and by Mandel and Van der Touw. The partially flexible model proposed by the latter authors allow to identify the electric polarizability calculated from electro-optical data to the specific dielectric increment measured in the high frequency range; both parameters appear to be molecular weight independent. The electric polarizability obtained from the Kerr effect would be originated in the induced dipoles caused by the delocalization of the bound counterions along rigid subunits whose length seems however to differ from the persistence length.


Spatial structures in a reaction-diffusion system--detailed analysis of the "Brusselator". Continuous dependence of spatially nonuniform concentration profiles for the 'Brussellator" reaction mechanims on the characteristic length of the system is given both for zero flux and fixed boundary conditions. Branches of solutions arising through primary bifurcation form closed curves. Secondary bifurcations giving rise to spatially asymmetric solutions exist for fixed boundary conditions. Results of a stability analysis of individual solutions are discussed. A method of composing complex spatial profiles for higher lengths from elementary solutions for smaller lenghts is suggested and tested in the case of zero flux boundary conditions. Emergence of subsequently more complex stable patterns in dependence on increasing length of the system suggests many similarities to gradual build up of complex morphogenetic patterns.


Current noise around steady states in discrete transport systems. Subject of this paper is the transport noise in discrete systems. The transport systems are given by a number (n) of binding sites separated by energy barriers. These binding sites may be in contact outer reservoirs. The state of the systems is characterized by the occupation numbers of particles (current carriers) at these binding sites. The change in time of the occupation numbers is generated by individual "jumps" of particles over the energy barriers, building up the flux matter (for charged particles: the electric current). In the limit n leads to infinity continuum processes as e.g. usual diffusion are included in the transport model. The fluctuations in occupation numbers and other quantities linearly coupled to the occupation numbers may be treated with the usual master equation approach. The treatment of the fluctuation in fluxes (current) makes necessary a different theoretical approach which is presented in this paper under the assumption of vanishing interactions between the particles. This approach may be applied to a number of different transport systems in biology and physics (ion transport through porous channels in membranes, carriers mediated ion transport through membranes, jump diffusion e.g. in superionic conductors). As in the master equation approach the calculation of correlations and noise spectra may be reduced to the solution of the macroscopic equations for the occupation numbers. This result may be regarded as a generalization to non-equilibrium current fluctuations of the usual Nyquist theorem relating the current (voltage) noise spectrum in thermal equilibrium to the macroscopic frequency dependent admittance. The validity of the general approach is demonstrated by the calculation of the autocorrelation function and spectrum of current noise for a number of special examples (e.g. pores in membranes, carrier mediated ion transport).


A mechanism for indirect allosteric action of charged effectors. A mechanism for indirect allosteric action of charged effectors on substrate binding to a macromolecule is proposed. It is accounted for by electrostatic interaction among effectors in the solution, away from their receptors. The possibility of the mechanism proposed is tested in the allosteric action of univalent salt and 2,3-diphosphoglycerate on oxygen binding to hemoglobin. A model for electrostatic interaction between these two effectors in the solution and for their overall effect on oxygen binding is introduced. The 2,3-diphosphoglycerate binding constant to deoxygenated hemoglobin as a function of univalent salt concentration and the median ligand activity  as a function of the concentration of univalent salt and 2,3-diphoshoglycerate are calculated and compared with experimental data. The obtained results indicate that electrostatic interaction in the solution may significantly contribute to indirect allosteric action of charged effectors.


Tension transients in fibrillar muscle fibres as affected by stretch-dependent binding of AMP-PNP: a teinochemical effect? The recovery in tension after release of a fibrillar muscle preparation as well as the fall in tension after restretch was found to be greater in presence of AMP-PNP than in its absence (rigor). The effect of AMP-PNP was concentration-dependent with an optimum at 0.1 mM corresponding to the dissociation constant of AMP-PNP from the myosin heads. This evidence supports the validity of the teinochemical principle which predicts a stretch-dependent AMP-PNP binding. The stiffness calculated per cross bridge was similar to that found by Huxley and Simmons (1971). It was further calculated that only 15% of the cross bridges are in a force-maintaining state in rigor.


Passive electrical properties of Halobacterium species. I. Low-frequency range. The electrical conductivity of suspensions of two species of Halobacterium was measured at low A. C. frequency. The results obtained from Halobacterium halobium suspensions show that the bacteria act as non-conducting particles. In contrast, the cells of a Halobacterium obtained from the Dead Sea (Halobacterium marismortui) had an apparently high conductivity which can be explained partly in terms of the cell-membrane being pierced by pores through which ions can move freely and partly in terms of highly concentrated cell ions, all of which are mobile.


Use of a new silylating agent for separation of bile acids and cholesterol by selected ion monitoring with the computer controlled intensity matching technique. Dimethylethylsilyl ether derivatives of human biliary bile acid ethyl esters and cholesterol were separated completely by gas chromatography and selected ion monitoring by use of the mixed stationary liquid phase of OV-101 and Dexsil 300GC (1:1). These derivatives could be prepared easily and subjected directly to gas chromatography mass spectrometry. Dimethylethylsilyl ethers of bile acids ethyl esters were eluted in regular order according to the number of hydroxyl groups when used with the non-polar stationary liquid phases. Lithocholic acid, a minor component of human bile, was identified easily by selected ion monitoring with the computer controlled intensity matching technique.


Simultaneous determination of diphenylhydantoin, mephobarbital, carbamazepine, phenobarbital and primidone in serum using direct chemical ionization mass spectrometry. A quantitative method for the simultaneous determination of five anticonvulsants in serum has been developed using chemical ionization mass spectrometry without prior chromatographic separation. The technique was shown to be rapid, simple and sensitive, allowing the routine analysis of 50 microliter of serum with good within-day and day-to-day precision.


The on column methylation of clonidine and p-hydroxyclonidine with trimethylanilinium hydroxide. The structures of the methylated clonidine derivatives formed by on column methylation with trimethylanilinium hydroxide are revised. The almost exclusive formation of derivatives of phenylimino-N,N-dimethylimidazolidine structure is explained in terms of a fast kinetically controlled reaction of substrate anions. The reliability of a stable isotope dilution assay for clonidine is discussed in view of these results.


Urinary metabolites of 4-isobutylphenylacetic acid studied by combined gas chromatography mass spectrometry. After ingestion of 4-isobutylphenylacetic acid three metabolites were identified in the urine, viz. 4-(2-carboxypropyl)phenylacetic acid, 4-(2-hydroxy-2-methylpropyl)phenylacetic acid and 4-(1-hydroxy-2-methylpropyl)phenylacetic acid. These metabolites were identified by gas chromatography and mass spectrometry. In the in vivo formation of the metabolites the isobutyl sidechain of the drug is attacked by omega1-hydroxylation, followed by further oxidation of the primary alcohol to a carboxyl group, by omega2-hydroxylation and by omega3-hydroxylation, respectively. It has been shown previously that two other drugs with an isobutyl sidechain, viz. 2-p-methoxybenzenesulphonamido-5-isobutyl-1,3,4-thiadiazole and 2,4'-isobutylphenylpropionic acid, are metabolized in an analogous way.


Selected ion monitoring assay for meclizine in human plasma. A method has been developed for the quantification of meclizine in human plasma using gas chromatography mass spectrometry. Pentadeuterated meclizine was synthesized and used as an internal standard. The method gave linear results over a concentration range of 5-200 ng ml-1 and was used to determine plasma levels of meclizine following administration to a male volunteer.


Natural 13C/12C ratio variations in human populations. Baseline data on the naturally occurring 13C/12C ratios of human tissue samples from several modern human populations are presented. Isotope ratios were determined for endogenous tissue samples (brain, liver and lung) from 20 routine unselected autopsy cases of residents of Long Island, New York. Comparable data were obtained from tissue samples from Bergen, Norway and Lucerne, Switzerland. Average values of 13C ratios reported in units of delta13C(0/00) relative to the PDB carbonate standard were -20.6 +/- 1.0 for 49 tissue samples from Switzerland, -20.7 +/- 1.0 for 21 tissue samples from Bergen, Norway and -16.2 +/- 1.0 for 89 tissue samples from Long Island, New York. These variations are discussed in terms of the isotopic carbon inventory in the respective diets of the populations sampled and also in terms of their implications for biomedical investigation.


Metabolism of the enantiomers of 2-hydroxy-N-cyclopropylmethylmorphinan in dog and man. The major metabolic pathway of the (-) enantiomer and the (+) enantiomer of 2-hydroxy-N-cyclopropylmethylmorphinan in dogs was shown to be conjugation with glucuronic acid and/or sulfate. Gas chromatography mass spectrometry, nuclear magnetic resonance spectroscopy and X-ray crystallography were used to identify additional metabolites of the two enantiomers in dog urine after hydrolysis with Glusulase. Metabolites of the (-) enantiomer were identified as 2-hydroxymorphinan and 2,7beta-dihydroxy-N-cyclopropropylmethylmorphinan. The major metabolites of the (+) enantiomer in hydrolyzed dog urine were identified as 2-hydroxymorphinan,2,3-dihydroxy-N-cyclopropylmethylmorphinan and 2-methoxy-3-hydroxy-N-cyclopropylmethylmorphinan. In addition, tentative or partial structures were postulated for three minor metabolites of the (+) enantiomer: 2-methoxy-3-hydroxymorphinan, a metabolite containing a hydroxyl group on either carbon 4, 5, 6 or 7 and a methylated catechol metabolite containing a hydroxyl group on carbon 4, 5, 6 or 7. Thus, the major oxidative pathways of the (-) enantiomer were N-dealkylation and aliphatic hydroxylation, while the (+) enantiomer mainly underwent N-dealkylation and aromatic hydroxylation, followed by phenolic methylation. Analysis of urine from a human subject administered the (-) enantiomer suggested that the metabolism of this isomer by man was similar to its metabolism by dog.


Phenylacetic acid in human cerebrospinal fluid and plasma: selected ion monitoring assay. Phenylacetic acid has been detected in human cerebrospinal fluid and plasma. Free acid and total acid values obtained after hydrolysis have been quantified as the pentafluorobenzyl ester by selected ion monitoring, using [2H7]phenylacetic acid as internal standard.


Applications of purification reactions for minimizing reaction-generated enzyme poisoning. A mathematical model has been employed to examine the interplay of reaction and mass transfer in immobilized enzyme systems involving reaction-generated enzyme poisions. Deactivation rates can be significantly reduced in some cases by catalyzing a purification reaction in which the poison is transformed into an innocuous substance. This conclusion in illustrated experimentally for reaction-generated H2O2 in  a continuous-flow stirred slurry reactor containing glucose oxidase immobilized on activated carbon.


Alterations in behavior resulting from persistent lymphocytic choriomeningitis virus infection. We have studied behavioral change in mice persistently infected as neonates with lymphocytic choriomeningitis virus. Open-field, electric shock startle, and locomotor behavior were measured on these persistently infected mice and normal controls when they were 2--6 months of age. The infected mice exhibited significantly greater latency to move in the open-field, were more sensitive to low current electric shock and were slightly less active when tested for 4 days in running wheels. Immunofluorescent examination of adult mouse brain 14 days after the initiation of persistent infection with cyclophosphamide (given 3 days after virus) demonstrated viral antigen in hippocampal and olfactory tissue. Behavioral results were interpreted in terms of direct effects of virus on the brain, perhaps altering certain critical neurophysiologic and neurochemical parameters. The possible relationship between limbic system pathology and human mental disorder is raised.


Serologic studies on schizophrenic patients. We studied the capacity of sera from schizophrenic patients and from normal blood bank donors to agglutinate sheep erythrocytes coated with extracts of human brain. Passive hemagglutination of coated erythrocytes was obtained with 36.4% of the assayed sera of the schizophrenia patients and with 11% of the control sera. Drug treatment did not seem to play a major role in the reactivity because the patients were either never treated before or a period of several weeks was allowed since treatment until blood was drawn. Furthermore, the analysis of sera obtained by sequential bleedings of patients on drug therapy showed that drugs did not affect the serologic activity.


[Comparative assessment of circulatory and respiratory maintenance by hemoglobin dissolved in plasma and contained in erythrocytes]. Basic values of blood circulation and respiration were compared in two groups of cats. The blood of group I animals was replaced by a 8% solution of human Hb completely free of stroma and procoaglulant activity. In group II animals the blood was diluted with polyglucine to the Hb level of 8 g%. The solution is well saturated in the lungs and releases O2 to tissues, but much less than Hb contained in red cells. The dissolved Hb did not completely meet the requirements of the organism in oxygen with the resultant hypoxia. Moderate anemic hypoxia caused by blood dilution with polyglucine was easily compensated. Hb solution can be considered as the basis or the first stage in the production of an oxygen carrier blood substitute.


[Interaction between the hypothalamo-hypophyseal system and the thyroid gland during different age periods]. Age peculiarities of interaction of the hypothalamo-hypophysial system and the thyroid gland with consideration to direct and feed-back control were studied. Significant alterations appear in old age in the hypothalamo-hypophysial system and the thyroid gland at the level of direct and feed-back control; there is an increase of sensitivity of the thyroid gland tissue to TSH, and of the hypothalamus-hypophysis--to the T4 effect. This rise of sensitivity is largely determined by the activation of the T4 deiodination processes in the adenohypophysis. The reactive capacity of the thyroid gland and of the hypothalamo-hypophysial complex to the corresponding influence is decreased.


[Increase in heat production by muscle contraction caused by 2,4-dinitrophenol]. By means of a highly sensitive thermometric method (1.10--50 C/mm) it was possible to demonstrate that the heat production during a single contraction of the isolated rat diaphragm increased under the influence of 2,4-dinitrophenol (DNP). Low DNP concentrations failed to produce any manifest changes in the resting muscle, but its action was distinct during contraction. With the same muscle contraction force DNP action was followed by an increase (about 1 1/2-fold) of heat production. This fact confirmed a supposition on the leading role of oxidation and phosphorylation uncoupling in the muscle cell respiratory chain in the increase of muscle contraction heat production in the animals after cold adaptation.


[Functional interaction between the determinant and other foci of epileptiform activity created in the cortex of both cerebral hemispheres]. It was shown in experiments on cats under nembutal anesthesia that creation of a hyperactive focus with a high excitation level in the orbital or coronary cortex of one hemisphere and of a number of foci in the neocortex of the contralateral hemisphere led to formation of a functional complex working in a unified regimen determined by the hyperactive focus activity. The latter plays the role of a determinant structure. Suppression of the determinant focus with nembutal was followed by a decay of the epileptic complex. Section of the corpus callossum (its rostral part) led to derangement in synch ronization of the work between the determinant and other epileptic activity foci. The results of investigation confirmed the conception on the role of the determinant structure in the nervous system activity.


[Induction of postural asymmetry in an intact recipient with an extract from the brain of a donor with such a syndrome]. An attempt was made of a direct transfer to the recipient of postural asymmetry originating after the removal of half of the anterior lobe of the cerebellum in rats. Postural asymmetry of the hind limbs proved to develop in spinal rats after subdural injection of brain extracts of the pathological donors below the spinal section level. Specificity of this asymmetry depending on the side of the cerebellar lesion was shown. The type of the recipient's asymmetry repeated the donor's asymmetry exactly. The brain extracts of control animals produced no asymmetry in the recipients. Additional evidence of the peptide nature of the factor stimulating postural asymmetry development was obtained: pronase inactivated the active brain extract.


[Noradrenaline and adrenaline concentration in the myocardium of persons who have died suddenly or from injuries]. To investigate mechanisms of sudden death the authors determined the content of noradrenaline and adrenaline in the myocardium of different heart sections in deceased persons by the fluorimetric method; similar studies of the myocardium of persons who died of trauma were conducted. Heterotopia in the noradrenaline content between the cardiac chambers proved to be considerably more pronounced in sudden death than in fatal trauma. The differences in the adrenaline and noradrenaline content in the heart chambers of persons who died of trauma and suddenly indicated the death mechanisms to be different in these cases.


[Erythropoietin and erythropoiesis inhibitor in neonatal hypoxia and normal conditions]. In 22 healthy newborns and in 31 newborns with transposition of the major arterial vessels (TMAV) erythropoietin and erythropoiesis inhibitor was studied on a model of polycythemic mice. Erythropoietin was not detected, whereas erythropoiesis inhibitor was revealed in the plasma and urine of 5--7-day-old healthy newborns. The newborns with TMAV displayed a rise of erythropoietin level up to the 14th day and its reduction during the period of from 14th to the 56th days. Erythropoiesis inhibitor was also found in the urine concentrates of the newborn with TMAV during the period of 3--4 weeks. The role of erythropoiesis inhibitor as a physiological regulator appearing in the blood of healthy and hypoxic newborns to normalize the erythropoiesis in the course of the initial weeks after birth is discussed.


[Functional state of the liver following massive transfusion of packed red cells]. Hepatic function was studied in experiments on 16 dogs after massive transfusion of red cell pack to ascertain the blood components influencing this function most. Massive transfusion of red cell pack failed to induce any significant changes in the excretory-absorbing protein forming function, and also in the content of transaminases. Hepatic function was markedly disturbed in a control group given massive transfusions of whole homologous blood. Results of investigations support the suggestion that one of the causes of hepatic function disturbances in "the syndrome of massive blood transfusion" was donor's and recipient's plasma protein incompatibility.


[Effect of in vivo thyroid hormones and IGL on protein synthesis in the mitochondria of thyroidectomized animals]. The authors studied the effect of triiodothyronine (T3) and IGL on the intensity of L-14C-tyrosine incorporation, and on the rate of protein of synthesis in the liver mitochondria of thyroidectomized rats, as well as on radioactivity of the liver amino acid poll. It was found that the intensity of L-14C-tyrosins incorporation into the protein of the liver mitochondria in thyroidectomized animals and the rate of protein synthesis in them was half that in sham-operated animals. T3 or IGL administration to thyroidectomized rats normalized protein synthesis in the liver mitochondria. According to all the biochemical indices studied the IGL effect was analogous to that of triiodothyronine. The absence of thyroid hormones in the organism of thyroidectomized animals, or T3 or IGL administration had no effect on the radioactivity of the free tyrosine pool in the liver tissue.


[Biosynthesis of reserpine-like substances in myocardium and other human and animal tissues]. Biosynthesis of reserpine-like substances with participation of such radioactive precursors as formiate, methyl groups of S-adenosylmethionine, tryptophane, reserpine, etc. occurred in the homogenates, microsomes, and cytozol of different human and animal tissues. As suggested, endogenous reserpine-like substances participated in the autoregulation of free and bound biogenic amines level.


[Effect of hypothermia on metabolism in the liver during its preservation]. Twenty experiments were conducted on dogs. The effect of hypothermia of different degree (from 18 to 20 degrees C and from 4 to 6 degrees C) on the carbohydrate metabolism and the extent of solubilization of hepatic enzymes (lactate dehydrogenase, glutamate dehydrogenase, urokaninase, DNA-ase, glucose-6-phosphatase) in prefusion-free preservation of the liver was studied. The preservation efficacy was assessed during the subsequent two-hour normothermic perfusion. A marked solubilization of the enzymes under study followed preservation of the liver at 18--20 degrees C; this indicated the loss of intactness of the cell membranes during the preservation. A moderate expenditure of the glycogen stores in the liver, and of sugar in the perfusate followed preservation of the liver at a temperature of 4--6 degrees C; this suggested an even suppression of hepatic metabolism and the prevalence of normal tissue respiration over glycolysis in the restoration of circulation in the liver.


[Concentration of acid proteins in the nuclei of rat hypothalamic neuron and glial cell nuclei during cold adaptation]. By means of two-wave length cytospectrophotometry the acid protein content per cell was determined in the nuclei of the neurons and their glial satellite cells of the medial peroptic area and the supraoptic nucleus of the hypothalamus of rats kept at 2--4 degrees C for 1, 3, 7, or 15 days (adaptation to cold). This colling resulted in an initial decrease in the nuclear acid protein content in the whole neuron-neuroglia system of the medail preoptic area with a gradual restoration to the normal by the 15th day of constant cooling. In the glial cells of this area the acid protein content increased temporarily above the control level before the restoration to the normal. A gradual accumulation of acid proteins and its following restoration to the control level was revealed in the neuron-neuroglia system of the supraoptic nucleus. By the 15th day of the adaptation to cold the content of neuronal and glial acid proteins of this nucleus became somewhat lower than in the control.


[Mechanisms of leukocyte activation during formation of leukocyte pyrogen]. The inhibotors of protein synthesis--actinomycin D and cycloheximide--inhibit endogenous pyrogen production by blood granulocytes in response to stimulation by the bacterial lipopolysaccharide and specific antigranulocytic serum and have no effect on the pyrogen release by exudate leukocytes. These results indicate that the mentioned inhibitors suppress the activation phase, but not the pyrogen labilization process.


[Phagocytic capacity of hematopoietic tissue stromal precursor cells]. A method of removal of phagocytising elements from the cell suspension by means of iron powder in magnetic field was used. Clonogenic fibroblast precursors of the hemopoietic tissue not belonging to histiocytes-macrophages, but referred to mechanocytes, were characterised by high phagocytic activity. Following Fe treatment less than 1% of clonogenic fibroblast precursors which gave rise to fibroblast colonies under conditions of monolayer cultures remained in the bone marrow cell suspension, and about 10%--in the spleen and the peritoneal exudate cell suspension.


[Changes in rat liver lysosomes following stimulation of recovery processes in the damaged organ by triton WR-1339]. The effect of a single injection of lysosomotropic agent--Triton WR-1339 on the properties of the rat liver lysosomes and the course of pathological process during chronic toxic hepatitis were studied. Triton WR-1339 administration was followed by a more rapid restoration of the liver structure and function. A possible mechanism of the favourable effect of Triton WR-1339 is discussed.


[Multicomponent system of estrogen-binding proteins of liver cytosol: species differences in rats, mice and guinea pigs]. Estradiol (E2) binding proteins from the liver cytoso-of mature male and female rats, mice, guinea pigs, and rabbits were investigated by gel filtration on Sepharose 6B columns. Components with Stokes radii (a) 6--7 and 2.5 nm which form specific stable complexes with E2 were found in female rats and female and male mice. The liver of male rats and male and female guinea pigs contain specific E2-binding proteins with a-about 6--7, 2.5 and less than 2.0 nm. E2 complexes with components having a values 6--7 and less than 2.0 nm relatively stable, whereas E2 complex with a component possessing a value about 2.5 nm is capable of dissociating completely within 45 minutes. It is suggested that at least some of the components of the discovered heterogenic populations of E2-binding proteins could participate in the estrogen signal reception by the liver.


[Long-term transplantation of mature sensory neurons]. The spinal ganglia were transplanted into the mesocolon of adult cats for periods of from 1 day to 9 months. About 30% of differentiated sensory neurons survived during the longterm transplantation. The intensive regeneration of the sensory neurons processes was characteristic of the transplanted neurons. Total myelinization of the regenerating nerves occurred during the 3rd--5th month. Potential regeneration capacity of the differentiated neurons and possibly of their prolonged transplantation were revealed.


[Differentiation of a transformed culture of L cells]. The cells of line L originated from the connective and adipose tissue of mice C3H were cultivated in nutrient medium with a 60% bovine serum. Some cells differentiated into adipose cells with formation of structures similar to normal adipose tissue. The occurring differentiation was evaluated by the formation of characteristic signetring cells whose cytoplasm was filled with neutral fat with a positive reaction for lipids in staining with a mixture of sudan III and sudan IV. The conclusion was drawn that prolonged existence of cells outside the organism (in vitro cultivation) and intracellular changes (accompanying the transformation), including those of mutation character, did not deprive the cells of their ability to differentiate.


[Activity and distribution of biogenic amines in thymus and spleen structures following administration of iso- and heterologous erythrocytes]. It was found that injection of heterological erythrocytes caused as soon as in 15 minutes displacement of noradrenaline from the efferent nerve endings and an essential re-building of metabolism of the central follicular cells and monoamine containing cells of the spleen marginal sinus, cortical fluorescent cells and mast cells of the thymus. Inversion of the medullary substance was revealed in the thymus.


[Effect of chronic pyrogenal stress on the mitotic regime and quantity of DNA-synthesizing cells in the epithelium of the cornea and tongue of white rats]. The effect of prolonged stress on mitotic regimen and the number of DNA-synthesizing cells in the corneal and tongue epithelium was studied on a model of pyrogenal stress. A five-day pyrogenal administration led to a 1.7-fold reduction of te number of mitoses in the corneal and tongue epithelium. Reduction in number of dividing cells was not associated with the change in the rate of mitosis. The percentage of pathological mitoses in the corneal epithelium of intact rats was 6.1, and it failed to change in stress. In control rats the labeled nuclei index in the corneal and tongue epithelium constituted 12.6 and 10.8. It was similar with the corresponding indices in experimental animals (12.2 and 12.2).


Fibrin formation: effect of calcium ions. Using laser fluctuation spectroscopy, a technique that measures particle size change in solution, the kinetics of fibrin clot formation from fibrinogen can be studied. With this technique the effect of calcium on the three distinguishable phases of clot formation, (1) proteolysis of fibrinogen, (2) fibrinogen-fibrin monomer complex formation, and (3) fibrin monomer polymerization, were investigated. Only a small change in the length of the induction period that results from the fibrinogen-fibrin monomer interactions was observed. However, there was a marked increase in the rate of fibrin monomer polymerization in the presence of calcium ions. These data show that calcium decreases the time required for fibrin formation from fibrinogen by markedly accelerating the phase of fibrin monomer polymerization.


Leukocyte-platelet interactions in a murine model of Chediak-Higashi syndrome. Chediak-Higashi (CH) syndrome, a genetic disease affecting man and other animals, is partially characterized by defective platelets that lack serotonin and dense bodies and by impaired leukocyte function where chemotaxis, degranulation, and bacterial killing are decreased. The effects of normal platelets containing serotonin and of reagent serotonin on the subnormal microbicidal activity of CH leukocytes were evaluated. The peripheral blood leukocytes of the beige mouse, an animal model with CH syndrome, were used with Staphylococcus aureus as the bacterial challenge. Addition of as few as two normal platelets/leukocyte resulted in normal levels of microbicidal activity of CH leukocytes. A similar normalization of leukocyte function was seen when 1-100-micrometer serotonin was added to the incubation mixture. Based on this work and work of others, a plausible explanation for these observations is that normal platelets interact with CH leukocytes, releasing serotonin, which results in reversal of the CH leukocyte defect in bacterial killing.


Absence of beta mRNA in beta0-thalassemia in Kurdish Jews. We report the characterization of the amount of beta mRNA in a Kurdish Jewish population with beta0-thalassemia using the same methods employed for characterization of the Catania and Ferrara beta0 patients. We found very low amounts of beta mRNA sequences, consistent with the presence of beta0-thalassemia of the beta mRNA-negative population type. In addition, no globin gene deletion was detected that could account for the absence of beta mRNA.


Fragmentation and myelin formation in hereditary xerocytosis and other hemolytic anemias. Erythrocytes from a heterogeneous group of hemolytic anemias have been found to release acetylcholinesterase-enriched fragments and show myelin forms during ATP depletion in vitro. The highest amount of fragmentation was found in hereditary spherocytosis and xerocytosis, two inherited membrane defects. Our data suggest ATP depletion plays a role in producing fragmentation or myelin forms. The addition of external CaCl2 1 mM had no effect on the degree of fragmentation. However, propranolol hydrochloride, a cationic anesthetic that does not prevent ATP depletion, inhibited fragmentation and the appearance of myelin forms in both hereditary spherocytes and xerocytes. A more detailed study of the xerocyte fragments showed that they had the same protein composition as those from normal red cells, primarily integral membrane proteins and glycoproteins. The red cells from patients with PNH and G6PD deficiency had the shortest survival in vivo (51Cr) and produced the smallest amount of fragmentation and myelin forms in vitro, whereas xerocytosis with only mild to moderate hemolysis in vivo was associated with the highest amount of myelin forms and membrane fragments in vitro.


Plasma cell leukemia (PCL): A report on 15 patients. Fifteen patients presenting with plasma cell leukemia (PCL) are reported in detail. The clinicopathologic features of PCL differ from typical myeloma and resemble those of acute leukemia: patients with PCL have less bone disease but a much higher incidence of organomegaly and tissue infiltration as well as diffuse marrow involvement and more pronounced pancytopenia. One of the reported patients developed meningeal plasma cell leukemia and is reported in detail. Cytomorphologic assessment of PCL cells showed nuclear immaturity and obvious nuclear/cytoplasmic asynchrony. Despite the use of cytotoxic agents known to be effective in myeloma, the prognosis in PCL is poor, and the median survival of the reported patients was only 2 mo.


Mechanisms underlying overshoot dilation after sympathetic denervation. (1) 30--60 sec after transection of the sympathetic chain, the diameter of both femoral artery and vein dilates to approximately 120% of the control diameter ('overshoot dilation'). Vessel diameter subsequently decreases and stabilizes with 5--10 min at a value of 108% of the original ('stabilized dilation'). (2) After treatment with norepinephrine-uptake-blocking drugs (cocaine, imipramine), the transient overshoot dilation is abolished and the diameter 1 min after denervation is identical to that at stabilized dilation. (3) It is proposed that (a) the stabilized rather than the transient overshoot dilation represents the loss of sympathetic control following following denervation and (b) the overshoot dilation reflects a transient decrease in transmitter concentration within the vessel wall, associated with a temporarily undiminished rate of neural reuptake activity persisting even in the absence of transmitter release.


Angiotensin analogs: effect of prostaglandin synthesis inhibitor. Structurally different inhibitors of prostaglandin synthesis reversed the antagonistic activity of the angiotensin II analog 1-sarcosine, 8-threonine angiotensin II. In isolated rabbit aorta, indomethacin or ETYA (eicosa 5, 8, 11, 14, tetraynoic) reversed the antagonism of the angiotensin II analog without affecting the dose response curves to angiotensin II. Both indomethacin and ETYA were able to reverse the tachyphylaxis to angiotensin II. Investigating the possibility that indomethacin could affect the binding of angiotensin II, it was found that at doses of indomethacin higher than 10(-5)M, binding of tritiated angiotensin to isolated adrenal cortical cells was reduced. It is postulated that indomethacin may have more than one effect on angiontensin, possessing a concentration-dependent effect on binding and prostaglandin synthesis.


In vivo study of microvascular wall characteristics and resting control in young and mature spontaneously hypertensive rats. This study was designed to determine if vessel wall hypertrophy and increased expression of sympathetic activity occur in the microcirculation during the development of hypertension. The cremaster muscle microvasculature of normal Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats was observed at age 5--7 weeks and 16--18 weeks. For age-matched WKY and SHR rats, the diameters, wall thicknesses and vessel wall cross-sectional areas for the majority of comparable types of arterioles were not significantly (p greater than 0.05) different. After denervation of the cremasteric muscle, the large and intermediate diameter arterioles of young WKY rats dilated significantly (p less than 0.05) more than did comparable vessels of SHR rats. In contrast, the dilation of comparable types of arterioles in mature WKY and SHR rats following denervation was not significantly (p greater than 0.05) different. The results do not support either abnormal vessel wall hypertrophy, vasoconstriction or increased expression of sympathetic activity in SHR rats compared to WKY rats up to age 16--18 weeks.


Ferritin in bone marrow and serum in iron deficiency and iron overload. Nonheme iron and ferritin in the bone marrow and serum ferritin was investigated in patients with iron deficiency anaemia or iron overload. As controls served patients without any disturbance of the iron metabolism. There is a precise correlation between the nonheme iron and ferritin in the bone marrow of patients with and without disturbance of iron metabolism. A correlation was also found between the ferritin in the bone marrow and the serum. Nonheme iron and ferritin in the bone marrow and serum ferritin was decreased in patients with iron deficiency anaemia. Conversely, the same parameters were increased in patients with iron overload.


[Iron determination by carbon rod atomizer (author's transl)]. A method is described for direct analysis of iron in proteins. The organic and inorganic matrices can be removed during the ashing step. The results obtained with simple aqueous standards were confirmed for all determinations by the standard addition method. The interpretation of the results by means of regression analysis showed, in dependence on the biological material (Haemoglobin, suspension of Microsomes, Cytochrome P 450), relative standard deviations between 4 and 20%.


Studies on Miltenberger class III, V, Mv and Mk red cells. I. Sodium-dodecylsulfate polyacrylamide gel electrophoretic investigations. The glycoproteins in erythrocyte membrane from individuals exhibiting the rare alleles at the MNSs blood group locus Miltenberger (Mi-) III, V, Mv and Mk were studied by sodium-dodecylsulfate polyacrylamide gel electrophoretic techniques. The results suggest that the genes Mi-III and -V give rise to the formation of Ss sialoglycoproteins whose electrophoretic mobilities are altered. The Mi-V alteration is additionally associated with a decreased MN glycoprotein content. The allele Mv leads to a decreased Ss glycoprotein content. Data on ordinary Mk and Mk/Mi-III red cells suggest that the gene complex Mk does not give rise to the synthesis of Ss glycoprotein.


Perthes disease conplicated by so called osteochondritis dissecans. A patient was followed for about 11 years from the onset of Perthes Disease (age 12). The radiographs during the period demonstrated the actual development of a free ossicle which was formed by resorption of a portion of the original femoral head, resulting in a wafer and subsequent enlargement by new bone formation. Changes of a similar nature have been described in idiopathic necrosis of the femoral heads in adults.


The response of the lower extremity to impact forces. I. design of an economical low frequency recording system for physiologic waveforms. An economical systems for the recording of low frequency physiologic waveforms on magnetic tape has been designed. This recording system has accurately reproduced human limb impact response data in the range of DC-350 Hertz.


Compression plate fixation of subtrochanteric osteotomies in children. Compression plates provide a reliable method for stabilizing subtrochanteric osteotomies (and fractures when indicated) in children. Apart from a standard compression set, no special appliances are required. The hazards and inconveniences of nail plates and external fixation devices are avoided.


Painless osteoid-osteoma in phalanx of finger. A case of unusual presentation and symptomatology. 1. Painless osteoid-osteoma is a very rare entity but must be considered. 2. Finger localization for this tumor has been reported in very few cases. Differential diagnosis with other tumors or osteomyelitis should be kept in mind. 3. Eng block excision in similar cases should be seriously considered. 4. While the reason for the absence of pain in some cases has not been precisely determined, the lack of nerve fibers in this case suggests that this may be an important factor.


Stress fracture after high tibial osteotomy: a case report. In summary, a case report is presented of the rare complication of a stress fracture of the tibia following a high tibial osteotomy. The stress fracture is thought to result from: (1) Local osteoporosis (2) Abnormal stress secondary to the malunion of the tibial osteotomy (3) Fibula non union resulting in impairment of the tibia to withstand cyclic loading with weight bearing.


Potentiation of vasoconstrictor responses by 3- and 4-aminopyridine. 1. In concentrations that are known to reduce potassium conductance in many excitable membranes, 3 and 4-aminopyridine (3-AP, 4-AP) potentiate vasoconstrictor responses of the isolated ear artery of the rabbit to noradrenaline and histamine. 2. 3- and 4-AP have no effect on the responses of potassium-depolarized arteries to noradrenaline, histamine or calcium. 3. The results suggest that the aminopyridines have no direct effect on the contractile machinery or on pharmacomechanical coupling, but cause potentiation by influencing electrical events at the cell membrane. 4. 4-AP causes a greater potentiation of the response te electrical stimulation than of the response to noradrenaline. This suggests that the aminopyridines may also cause an increase in the amount of noradrenaline released in response to sympathetic nerve stimulation.


Relationship between atrial and ventricular rates of fibrillation and cardiac contractile tissue effective refractory periods in the dog. 1 During total cardiopulmonary bypass, acetylcholine-, isoprenaline-, ouabain- and quinidine-induced variations in the atrial and ventricular rates of fibrillation were studied and compared with the variations in effective refractory periods (ERP) of atrial and ventricular contractile tissue obtained under the same experimental conditions. 2 Acetylcholine significantly shortened the ERP and accelerated the rate of fibrillation in the atrium but did not provoke any change in ventricular tissue. A parallel decrease in atrial and ventricular ERP and a parallel increase in atrial and ventricular rates of fibrillation were observed with isoprenaline. 3 Ouabain exerted a biphasic effect on the atrium, with an initial decrease in the ERP and an initial acceleration of the rate of fibrillation. It produced only a slight decrease in the ventricular ERP and no significant variation in the ventricular rate of fibrillation. 4 Quinidine induced a greater increase in the ERP and a greater slowing of the rate of fibrillation in the atrium than in the ventricle. 5 The variations in percentage change of refractoriness and rate of fibrillation were strictly correlated: r = 0.89 (P less than 0.001); the equation of the regression line was y = --0.86 x --2.98.


Comparison of the electrocortical changes induced by (+)-amphetamine and chlorpromazine when perfused directly into the dorsal raphé nucleus of the cat. 1 (+)-Amphetamine mimicked the intermittent and sustained electrocortical desynchronization produced by (-)-noradrenaline (NA) when perfused directly into the dorsal raphé nucleus of cat encéphale isolé preparations. 2 The effects of amphetamine or NA were abolished or significantly attenuated by prior application of (-)-propranolol. 3 The effect of amphetamine, but not that of NA, was blocked by prior applications of guanethidine or chlorpromazine (CPZ). 4 Desmethylimipramine (DMI) produced dose-related changes in electrocortical activity which were similar to those induced by NA when applied to the same sites within the dorsal raphé nucleus. 5 DMI potentiated the effects of both amphetamine and NA, but guanethidine only abolished the DMI-induced potentiation of the amphetamine response. 6 (-)-Propranolol, guanethidine and CPA produced a short period of electrocortical desynchronization at the beginning of the perfusion period before antagonism of the amphetamine response was apparent. 7 The results suggest that CPZ and amphetamine have an action within the dorsal raphé nucleus possibly related to noradrenergic terminals.


A comparison of nicotine and structurally related compounds as discriminative stimuli. 1 Of seven nicotine-like compounds tested as discriminative stimuli in the rat, only 3-pyridyl-methylpyrollidine (3-PMP) generalized to the stimulus effects of nicotine. 2 3-PMP caused equivalent nicotine-like responding at a dose (800 microgram/kg) approximately 4 times that used for the original nicotine discrimination (200 microgram/kg). The ED50 for 3-PMP was about 5 times that for nicotine. 3 Testing of the compounds as possible antagonists of the nicotine-elicited cue were negative. 4 The nicotine-like cue produced by an 800 microgram/kg injection of 3-PMP was effectively blocked by mecamylamine but not by hexamethonium or atropine. Thus, 3-PMP appears to produce generalization to the nicotine cue via action on central nicotinic-cholinoceptors as has been previously reported for the nicotine discriminative stimulus. 5 Mecamylamine blocked the stimulus-effects of 3-PMP (800 microgram/kg) and of nicotine (200 microgram/kg) with an ED50 of 0.32 and 0.20 microgram/kg respectively.


Prostaglandin production by macrophages and the effect of anti-inflammatory drugs. 1 Macrophages derived from peritoneal cavity inflammatory exudates of guinea-pigs produced substantial amounts of prostaglandin E2-like activity during in vitro culture, so providing the basis for an experimental model of prostaglandin production during inflammatory reactions. 2 Dose-related inhibition of prostaglandin biosynthesis was demonstrated by 16 acidic non-steroidal anti-inflammatory drugs. 3 Seven anti-inflammatory glucocorticosteroid preparations inhibited prostaglandin production in a dose-related manner. The relative potencies of dexamethasone, prednisolone and hydrocortisone were consistent with clinical anti-inflammatory ranking. Cortisone, however, failed to inhibit macrophage prostaglandin production. 4 Three other agents used in the treatment of inflammatory joint diseases were examined. Sodium aurothiomalate inhibited prostaglandin production, although higher concentrations were toxic to macrophages. D-Penicillamine did not affect macrophage prostaglandin production. Colchicine, in contrast, enhanced prostaglandin production at some concentrations. 5 The probable significance of macrophages as a source of prostaglandins, during inflammatory responses, is discussed.


Comparison of the responses of single cortical neurones to tyramine and noradrenaline: effects of desipramine. 1 The technique of microelectrophoresis was used in order to compare the actions of tyramine and noradrenaline on single neurones in the cerebral cortex of the rat.2 Tyramine could both excite and depress cortical neurones. Each tyramine-sensitive cell was also sensitive to noradrenaline. There was a high correlation between the directions of responses to tyramine and noradrenaline, most cells excited by tyramine being excited by noradrenaline, and most cells depressed by tyramine being depressed by noradrenaline.3 In the case of both excitatory and depressant responses, tyramine appeared to be less potent than noradrenaline.4 Tyramine evoked ;slower' responses than noradrenaline, both the latencies to onset and the recovery times being longer for responses to tyramine than for responses to noradrenaline.5 When the rates of release of tyramine and noradrenaline from micropipettes were measured in vitro, no significant difference could be observed between the transport numbers of the two drugs. Thus the difference in potency between the two drugs, and the difference in the time courses of responses to the two drugs, are presumably of biological origin.6 Desipramine could discriminate between neuronal responses to tyramine and noradrenaline: responses to tyramine were antagonized, while responses to noradrenaline were either potentiated or unaffected. Responses to DL-homocysteic acid were not affected by desipramine.7 The results are consistent with the hypothesis that tyramine is an indirectly acting sympathomimetic amine in the brain, and desipramine acts by blocking the uptake of both tyramine and noradrenaline into presynaptic noradrenergic nerve terminals.


The mechanism of the relaxant effect of 2-2'-pyridylisatogen on the isolated taenia of the guinea-pig caecum. 1 2-2'-Pyridylisatogen tosylate (PIT) slowly relaxed taenia caeci preparationg of the guinea-pig in a concentration-dependent manner (threshold 2.5 muM). The relaxant effect did not show tachyphylaxis.2 The relaxation was not affected by tetrodotoxin (0.3 muM), guanethidine (17 muM) nor by a combination of phentolamine (36 muM) and propranolol (4 muM)3 In taenia caeci preparations suspended in K(+)-depolarizing, Ca(2+)-free Ringer, addition of Ca(2+) (0.1 to 30 mM) resulted in a slow contraction. PIT (50 muM) and papaverine (15 muM) antagonized these contractions, whereas indomethacin (28 muM) was ineffective.4 Although PIT (50 muM for 30 min) caused a relaxation of the taenia, and, when the tone of the preparations was restored with carbachol, antagonized adenosine 5'-triphosphate (ATP)-induced relaxations, relaxation of the taenia with papaverine (30 muM for 5 min) did not antagonize ATP-induced relaxations. It is concluded that the relaxant and ATP-receptor blocking actions of PIT are independent properties of the compound.


A comparison of the antifertility effects of alkylating agents and vinca alkaloids in male rats. 1 The anti-fertility effects of cyclophosphamide, nitrogen mustard, vincristine and vinblastine were studied and compared in male rats. 2 The effects of the drugs on body weight and haematological values were used to monitor the pharmacological actions of the drugs. 3 All four drugs impaired fertility, the severity of the impairment depending on dose and duration of treatment. 4 Testicular size and histological appearances remained mostly normal, even in infertile animals, but seminiferous tubules were fewer in number and maturation arrest at the spermatid level was evident in some sections. 5 Recovery of drug-induced infertility occurred in 64% of treated animals, 9 to 40 weeks after cessation of treatment. 6 Morbidity and mortality were much higher with alkylating agents than with vinca alkaloids for approximately similar degrees of impairment in fertility.


A test of the schizophrenic's ability to process information in one or two sensory modes. Twenty-three schizophrenics, ten psychiatric controls, and 17 normal controls were used to test the hypothesis that schizophrenics suffer a deficit in their ability to integrate information from different sensory modes. The task involved identifying auditory, visual, or mixed (auditory and visual) patterns which had previously been equated in difficulty for normal subjects. Mean error scores were greatest for schizophrenics and least for normals with psychiatric controls in between. Moreover, the schizophrenics did equally well whether the task was visual, auditory, or mixed. Thus, schizophrenics showed no deficit specific to the synthesis of information from two different sensory modes.


Some psychological, educational and criminological variables related to recidivism in delinquent boys. The HDHQ, 16 PF and PSI were administered to 315 detainees at Medomsley Detention Centre, Durham, along with tests of intelligence and attainment, and measures of previous criminal history. One hundred and ninety-one boys were subsequently reconvicted within two years of their release. They were found to have lower scores on reading and arithmetic tests, to show a greater degree of extrapunitive hostility and to score more highly on tests of social non-conformity. Recidivists had also begun their criminal careers at an earlier age than non-recidivists and had committed significantly more previous offences.


Simple behaviour rating scales for maximum security patients: development and validation. An outline is given of objective behaviour rating scales developed for use by nurse custodians in the maximum security hospital setting. Four independent scales are described: (a) antisocial belligerence, (b) disorientation, (c) withdrawal and (d) personal hygiene. The scales gave high test-retest and inter-rater reliabilities. Various indications of validity and potential usefulness of the scales are given. In particular, a probable relationship of the scales (a) and (c) with an impulsivity/overcontrol dimension is suggested-this relating to the type of aggressive offending recorded.