Sequences at the somatic recombination sites of immunoglobulin light-chain genes.

The entire nucleotide sequence of a 1.7-kilobase embryonic DNA fragment containing five joining (J) DNA segments for mouse immunoglobulin kappa chain gene has been determined. Each J DNA segment can encode amino acid residues 96--108. Comparison of one of the five J DNA sequences with those of an embryonic variable (V) gene and a complete kappa chain gene permitted localisation of a precise recombination site. The 5'-flanking regions of J DNA segments could form an inverted stem structure with the 3'-non-coding region of embryonic V genes. This hypothetical structure and gel-blotting analysis of total embryo and myeloma DNA suggest that the somatic recombination may be accompanied by excision of an entire DNA segment between a V gene and a J DNA segment. Antibody diversity may in part be generated by modulation of the precise recombination sites.


A kappa-immunoglobulin gene is formed by site-specific recombination without further somatic mutation.

The active gene for a kappa light chain is formed by a somatic recombination event that joins one of several hundred variable region genes to one of a series of recombination sites (J-segments) encoded close to the kappa constant region gene. The nucleotide sequences of cloned germ line and somatically recombined genes define the precise organisation of these genetic segments and the site  and nature of the recombination event that joined them. Apart from somatic recombination, no further alteration of ther germ line sequence has occurred. The J-segment is of special interest as it encodes signals for both DNA and RNA splicing and provides a means of generating further immunoglobulin gene diversity.


Lack of evidence for an inhibitory role played by tuberoinfundibular dopaminergic neurons on TSH secretion in the rat.

The role of dopamine (DA) in the control of thyroid stimulating hormone (TSH) secretion in basal or cold stimulated conditions was investigated by using pharmacological or neurosurgical tools. The intraventricular injection of DA (5 micrograms/animal) or the subcutaneus (s.c.) injection of a dopaminomimetic agent failed to induce changes of TSH plasma levels in normal or in cold stimulated conditions. The same results were obtained by intraperitoneal (i.p.) administration of haloperidol, a blocker of dopaminergic receptors. The complete deafferentation of hypothalamus, which causes degeneration of norepinephrinergic nerve endings and leaves the DA tuberoinfundibular system unaffected, prevented the TSH release evoked by cold exposure. alpha-Methyl-p-tyrosine (alpha-MpT) (250 mg/kg i.p.), which causes a remarkable reduction of DA in the median eminence (ME) of deafferented animals, was unable to restore the TSH response to cold. Collectively these results seem to suggest that DA does not play a significative role in the control of TSH secretion in the rat.


Alterations in cortical oxygen tension during the development of ischemic cerebral edema in primates (Macaca mulatta).

With a closed head primate stroke model, acute cerebral ischemia limited to the middle cerebral artery (MCA) territory was produced by macrosphere embolization of the internal carotid artery bifurcation. Measurements of the oxygen tension (PO2) at the cerebral cortical surface were obtained by continuous on-line mass spectrometry. Percentage of dry weight and tissue sodium, potassium, and chloride concentrations from ischemic and nonischemic hemispheres were determined at various times. With this preparation, we registered the precise onset of cortical surface PO2 depletion, which showed an exponential downward trend (fast component from 0 to 5 minutes, t 1/2 = 0.8 minute, rate of change = 89% per minute; slow component from 5 to 240 minutes, t 1/2 = 285 minutes, rate of change = 0.3% per minute). After the onset of cerebral ischemia, there was an immediate fall of the cortical surface PO2 with reductions of more than 45% at 5 minutes before definite hemiparesis and electroencephalographic abnormalities were recognized. During the secondary phase from 5 to 240 minutes the cortical surface PO2 fell by only an additional 23% of the steady state. Even so, when cortical surface PO2 was maintained at this critically low level, the earliest cerebral cortical edema was evident 180 minutes after MCA occlusion. Thereafter, progressive accumulation of edema fluid in the cortex (90 to 170.8 microliters per g of tissue) and in the white matter (19 to 46.2 microliter per g of tissue) was detected by the end of 240 minutes of cerebral ischemia.


Cranioplasty: a review of 1030 cases of penetrating head injury.

A total of 491 cranioplasties performed in a population of 1030 cases of penetrating head injury are reviewed. The morbidity rate was 5.5%, and the mortality rate was 0.2%. The clinical criteria of improving cosmetic defects and restoring craniocerebral protection are established, based on the location and size of the skull defect. Cranioplasty after penetrating head injury should be deferred for a minimum of 1 year to control morbidity. Complication of the original injury and surgical debridement increase the morbidity rate of cranioplasty. Post-traumatic epilepsy is not related to skull defects per se; neither is it affected by cranioplasty. Acrylic is an acceptable cranioplasty material if there is strict adherence to good surgical technique.


[Current trends of complementary therapy in radical surgery of colo-rectal cancer].

Large surgical series are agreed on the fact that the prognosis for radically operated colorectal cancer has improved little in the last twenty years. Reasons for these failures are, of course, local or remote recurrences. To improve the number of stable cures, experiments have been carried out with complementary or coadjuvant techniques whose purpose is to limit intra-operative dissemination of the tumour and to monitor the number of cancer cells that might remain after radical surgery. Such techniques have been applied at preoperative, intra-operative and post-operative phases. Results obtained so far have been uncertain but seem to point to the usefulness of intraoperative procedures in reducing the number of local recurrences and of postoperative chemotherapy with 5 FU which has improved five-year survival indices by 5-7%.


[Multiple diverticulosis of the small intestine].

A case of jejunum-ileum multiple diverticulosis observed during a cholecystectomy due to cholelithiasis, is reported. Stress is laid on this unusual localization of diverticulosis in the small intestine. The clinical picture can be silent or present an acute or chronic symptomatology and radical surgical treatment can performed or not. When the disease involves all the intestine, without presenting serious inflammatory phenomena and without clinical symptoms (as in the case observed), medical and not surgical treatment can be envisaged.


[Current status in transplantation of the endocrine pancreas in the treatment of diabetes mellitus 2. Transplantation of fetal pancreas].

The latest findings support hypotheses that diabetes complications are secondary to metabolic control which current insulin therapy is unable to render constant. Surgical attempts to transplant the pancreas and Langerhans islets in the treatment of diabetes mellitus are reviewed and special attention paid to the use of the foetal pancreas which has proved particularly suitable in preventing microangiopathic complication. Comments are based on a careful review of the literature, made in the light of personal experience.


Projection of precentral motor cortex upon nucleus medialis dorsalis thalami in the monkey.

The efferent connections of the lateral aspects of the precentral, premotor and granular frontal cortex were reexamined in 12 monkeys (Macaca fascicularis) by means of anterograde labelling techniques using radioactive proline and leucine. A distinct projection of the precentral gyrus upon the paralamellar portion of the nucleus medialis dorsalis (MD) was observed. The somatotopic arrangement within this projection is less well defined than within the ventrolateral thalamic complex. The facial division of area 4 has not only a marked ipsilateral but in contrast to the body representation also a distinct if much weaker contralateral projection. No label was found in MD after injections in the postcentral gyrus. Thus, MD represents a thalamic link between agranular (motor) and granular (association) cortex of the frontal lobe.


Interlaminar connections of tree shrew visual cortex.

The intracortical projections of neurons in layers II and upper III of tree shrew visual cortex were studied after terminal lesions in the supragranular layers of area 17. Examination for terminal degeneration was made using ultrastructural techniques. The majority of degenerating terminals were found in layers V and, to a lesser extent, VI, and were presynaptic to neural profiles in the following distribution: 80.5% on spines of small to medium size dendrites, 19% on dendrite shafts, and less than 1% on neuronal perikarya. Degenerating axons coursed in vertical bundles through layers III, IV, V and VI. These findings are similar to those previously described in rat visual cortex.


Cells of origin of the frontal projections to magnocellular and parvocellular red nucleus and superior colliculus in cynomolgus monkey. An HRP study.

Cells of origin of frontal cortical projections to parvocellular and magnocellular red nucleus (MRN) and superior colliculus were identified by means of retrograde HRP transport. The cells projecting to parvocellular red nucleus (PRN) are mainly located in areas 6 and 4, and are situated in the upper part of layer V, i.e. above the Betz cells, while those projecting to MRN are mainly located posteriorly in area 4, and are situated deep in layer V, i.e. at the level of the Betz cells. The neurons projecting to superior colliculus are located deep in layer V of areas 9, 8 and 6.


Localization of motoneurons innervating the posterior belly of the digastric muscle: a comparative anatomical study by the HRP method.

Motoneurons innervating the posterior belly of the digastric muscle were identified in the monkey, cat, dog, guinea pig and rat by the HRP method. After injections of horseradish peroxidase (HRP) into the posterior belly of the digastric muscle, two groups of HRP-labeled motoneurons were observed; the rostral group was seen as a small cluster of neurons in the lateral reticular area along the medial border of the descending root of the facial nerve, and the neurons of the caudal group were distributed among the ascending root fibers of the facial nerve. The distribution pattern of these neurons corresponded to that of the accessory facial nucleus neurons. The accessory facial nucleus was lacking in the rabbit in which the posterior digastric (PD) muscle is nonexistent.


Neuronal activity in the cortical supplementary motor area related with distal and proximal forelimb movements.

Monkeys were trained to perform two different motor acts, one involving muscle activity in distal forelimb muscles and the other in proximal forelimb and shoulder girdle muscles. After confirming spatial and temporal dissociation of muscle activity in the two motor acts, single unit activity in the supplementary motor area (SMA) was recorded. SMA neurons related with the distal and proximal forelimb movements were found to be arranged rostrocaudally with a considerable overlap. In the overlapping region, neurons related with the distal movement were located more deeply.


Neurons responding to visual stimuli in the frontal lobe of macaque monkeys.

Responses to visual stimuli of single cortical neurons in arcuate and prearcuate regions were studied in 6 immobilized macaque monkeys. Neurons responding to visual stimuli were found in both regions, some of them responded to conventional light stimuli, others required more complex visual stimulation. The former were found posteriorly in the arcuate region, the latter anterioly and in the prearcuate region. According to their functional properties the latter neurons were subdivided into: (a) neurons responding to stimuli near the eyes; (b) neurons triggered by complex visual stimuli; (c) neurons inhibited by visual stimuli.


Carbonic anhydrase activity in myelin fractions from rat optic nerves.

The carbonic anhydrase activity of myelin fractions isolated from the optic nerves of adult and immature (20-day-old) rats was examined. The specific activity in both total homogenate and myelin fractions was about 2-fold higher in adult than in immature animals and at both ages, the activity in the homogenate was higher than in myelin. After subfractionation by zonal gradient centrifugation, it was shown that carbonic anhydrase activity was greatest in the heaviest myelin particles at both ages. These data are consistent with the hypothesis that a small proportion of the total enzyme activity is localised in myelin.


Age-dependent changes in the inactivation of thyrotrophin-releasing hormone by different areas of rat brain.

Age-dependent changes in the inactivation of thyrotrophin-releasing hormone (TRH) were investigated in two subcellular fractions prepared from hypothalamus, thalamus, cortex and cerebellum of male rats. It was found that, in both supernatant and particulate fractions from the four brain areas, enzyme activity increased to a peak at 10-25 days of age and then decreased gradually until adult levels were reached. The changes in TRH degradation observed may be related to alterations in hypothalamic TRH content with age and to maturation of the tripeptide's putative neurotransmitter/neuromodulator function.


[Electrophoretic and immunofluorescent study of lactate dehydrogenase isoenzymes during eye regeneration in adult tritons].

The spectrum of LDH isozymes was studied at the successive stages of retinal regeneration from the pigment epithelium and lens cells from the iris margin in the adults Pleurodeles waltlii. The combination of two methods, electrophoresis and immunofluorescence, has revealed the slow and rapid LDH isozymes with different intensity of histochemical staining in cells of the tissues under study (pigment epithelium, retina, iris and lens). During the regeneration the spectra of LDH isozymes peculiar to the pigment epithelium and iris and characterized by the predominance of slow forms were substituted by those peculiar to the retina and iris and characterized by the predominance of rapid forms. The rearrangement is realized in the proliferative phase during the transformation of one cell type into another.


Sickled erythrocytes, hyphema, and secondary glaucoma: II. Injected sickle cell erythrocytes into human, monkey, and guinea pig anterior chambers: the induction of sickling and secondary glaucoma.

Injection of sickle cell erythrocytes (SS, SC, Sthal, and AS) into the anterior chambers of living human, monkey, and guinea pig eyes resulted in conversion of erythrocytes to the sickled configuration. Immune responses did not appear to play an important role in influencing this phenomenon. The number of cells sickled was directly related to the concentration of hemoglobin S. In human and monkey eyes, the severity of elevated IOP appeared to be related to the type of cells injected and their concentration of hemoglobin S. Even the ordinarily benign genotype of sickle cell trait demonstrated sickling in the anterior chamber and elevation of the IOP.


Sickled erythrocytes, hyphema, and secondary glaucoma: VII. The passage of sickled erythrocytes out of the anterior chamber of the human and monkey eye: light and electron microscopic studies.

Sickled erythrocytes leave the anterior chamber of human and monkey eyes by several mechanisms: intracameral and intratrabecular hemolysis and phagocytosis; entry into and phagocytosis within the iris and ciliary body; and passage into Schlemm's canal. Sickled erythrocytes used as biologic tracers allowed definite confirmation, for the first time in the human, that intracameral erythrocytes can enter Schlemm's canal in the orthograde direction. Erythrocytes appeared to traverse the inner wall of Schlemm's canal through the cytoplasm of individual endothelial cells, rather than between adjacent endothelial cells -- a mechanism similar to that employed by red and white blood cells elsewhere in the body. Although some sickled erythrocytes did pass into Schlemm's canal, considerable obstruction appeared to occur at the corneoscleral meshwork, juxtacanalicular connective tissue, and inner wall of Schlemm's canal, caused largely by the elongated, rigid nature of the sickled cells. Total blockage of Schlemm's canal was not observed.


Chemical carcinogenesis of submandibular salivary gland in BALB/c mice and syngeneic passage of the tumor.

Twenty-two male BALB/c mice were used in this investigation. A pellet of dry 9,10-dimethyl-1,2-benzanthracene powder was implanted in the submandibular salivary gland. Fifteen epidermoid carcinomas and four sarcomas were induced within a period ranging from 7 to 15 weeks. Epidermoid carcinomas were sucessfully transplanted into syngeneic mice.


[Nitrogen balance in premature babies during parenteral nutrition (author's transl)].

This paper represents a continuation of research into the nitrogen (N) balances in seriously premature babies. During parenteral nutrition an increased amount of 400 mg N/kg body weight/24 hrs. was administered in the form of L-aminoacids together with glucose and fat emulsion. No change in the amount of retained aminoacids occurred (some 80%). On the other hand several increased values of N-metabolites demonstrate that this dosis of aminoacids can be considered as the maximal value.


[Kryptophthalmus syndrome (author's transl)].

This peper describes the rare cryptophthalmus syndrome combined with several other malformations of the urogenital tract and of the nose, in addition to dyscephalia and cutaneous syndactilism of fingers and toes. Because of a high incidence of parental consanguinity autosomal recessive heredity is discussed.


Organochlorine residues in harp seal (Phagophilus groenlandicus) tissues, Gulf of St. Lawrence, 1971, 1973.

Levels of p,p'-DDT, p,p'-TDE, p,p'-DDE, dieldrin, polychlorinated biphenyls (PCBs), and HCB were determined in certain tissues of 31 harp seals (P hagophilus groenlandicus) taken from the Gulf of St. Lawrence during 1971 and 1973. The seals ranged in age from less than two weeks to 18 years. Mean concentrations of PCBs and sigma DDT in the various tissues were about the same sigma DDT levels were 1.64--9.88 ppm in adult seal blubber and 1.08--3.73 ppm in seal pup blubber. Organochlorine levels in harp seal samples taken in 1973 were similar to those reported by other workers for samples collected in the Gulf of St. Lawrence during 1967-71.


Nationwide residues of organochlorine compounds in starlings (Sturnus vulgaris), 1976.

Organochlorine pesticide and PCB residues in starlings from 126 sites within the contiguous 48 states were monitored during fall 1976. The average nationwide level of DDE and PCBs has increased significantly since 1974, but the number of sites reporting PCB residues has decreased fivefold. Dieldrin residues have remained unchanged since 1974. Highest DDE levels occurred in samples from parts of Arizona, Arkansas, California, Louisiana, and New Mexico.


Effects of adrenaline administration on the activity of glycogen metabolizing enzymes in different muscle types.

Adrenaline administration which leads to glycogen changes different in fast and slow twitch muscles (Gorski, 1978) causes very similar acute changes in the activities of glycogen synthase I and of glycogen phosphorylase 'a' in these two types of rat muscle.


[Major metabolic disturbances occur in diabetic patients whether they are obese or not (author's transl)].

The authors analyzed the effects of obesity/non-obesity in 162 epidoses of severe metabolic disturbances. Ketoacidosis and hypoglycaemics comas were more frequent in the non-obese group of diabetics, who were often insulin treated; whereas hyperosmolar coma and lactic acidosis were frequent in the obese group of diabetics, usually not treated with insulin. In the obese group both advanced age as well as a higher frequency of degenerative complications impaired the prognosis of these metabolic accidents. However the mortality rate was not significantly different in the two groups of patients. Despite the importance of the weight balance in the natural history of diabetes mellitus, it did not seem to influence the clinical aspects nor did it modify the therapeutic management of the major metabolic disturbances which occur in diabetes.


[Islet cell transplantation and diabetes (author's transl)].

It is now apparent that transplantation of islet cells is biologically feasible in experimental animals utilizing adult neonatal or fetal islet cells and employing many different sites for implantation of the islet cells. It is reasonable to expect that with successful acquisition of new basic information in immunology, endocrinology, metabolism and developmental biology islet cell transplantation should be used as a therapeutic approach to human diabetes.


[Alcoholic ketoacidosis. One case (author's transl)].

Severe ketoacidosis sometimes develops in chronic alcoholics after increased alcohol intake associated with dietary restriction. This particular case was unusual from two standpoints: a considerable, prolonged and unexplained increase in serum free fatty acid, and discordance between the degree of ketonaemia and an abundant liver glycogen load.


Incorporation of lysine into Y base of phenylalanine tRNA in Vero cells.

Vero cells, a line derived from African green monkey kidney, contains a hypermodified base, called Y, adjacent to the 3' end of the anticodon of tRNAPhe. Two types of evidence are presented suggesting that lysine is involved in biosynthesis of Y base in these cells. First, when Vero cells are starved for lysine, a new, early-eluting species of tRNAPhe which lacks the fully modified Y base can be detected by reversed phase chromatography (RPC-5). After addition of lysine to the medium, this new species disappears. Second, when these cells are grown in low-lysine medium and then exposed to [3H]lysine, radioactivity from the lysine comigrates with tRNAPhe. The Y base can be selectively excised from tRNAPhe by incubation at pH 2.9, and extracted into ethyl acetate. Thin-layer chromatography of acid-excised material from these cells reveals that lysine-derived radioactivity comigrates with genuine Y base from calf liver tRNAPhe and the acid-excised tRNA no longer contains radioactivity. These results are consistent with the model that lysine is a structural precursor of Y base in tRNAPhe of Vero cells.


Transfer RNATyr of melanoma tissues and cells: relevance to melanin synthesis?

The tRNA present in swine melanoma tumor tissue and normal gray skin tissue were compared by aminoacylation of the unfractionated tRNA preparations. Of the seventeen amino acids studied, seven showed differences in rate of acceptance to tRNAs from normal and tumor tissues; the tRNAs of two amino acids, tyrosine and glycine, showed dramatic three fold increases in melanoma tumor. As melanin biosynthesis proceeds from tyrosine oxidation the investigations focused on the increase in tyrosine tRNA. Kinetic analysis of tyrosine aminoacylation to normal and melanoma tRNAs revealed no differences. Analysis of the isoaccepting species of tRNATyr from normal skin and melanoma tumor tissues identified three isoacceptors; tRNATyr, represented the predominant species in normal gray skin, while tRNA2Tyr predominated in melanoma tumor tissue. The tyrosine acceptances by tRNAs from three human melanoma cell lines were analyzed and found to be variable, but isoaccepting species analysis of the tRNATyr of these three cell lines still showed a correlation between the preponderance of tRNA2Tyr and extent of tyrosine acceptance. Additionally the enzymatic activity for the oxidation of tyrosine was found to be related to tyrosine acceptance and tRNA2Tyr predominance..


The conformational properties of ribosomal protein S1.

The proton NMR spectrum of S1 reveals that S1 has considerable tertiary structure in physiological buffers, but more structural flexibility than normal for globular proteins. S1's NMR spectrum is independent of the method of preparation.


Effect of lucanthone (miracil D) on transcription of ribosomal RNA genes from Tetrahymena in vivo and in vitro.

Addition of lucanthone (1-5 mug/ml) to cultures of Tetrahymena results in a preferential inhibition of the synthesis of ribosomal RNA. Transcriptional studies with isolated nucleoli from Tetrahymena demonstrate that the endogenous RNA polymerases of the r-chromatin (chromatin form of rDNA) do not recognize the normal termination and move into the spacer region distal to the terminator in the presence of lucanthone. This is shown by hybridization of the transcript synthesized in the presence of the drug to restriction fragments of rDNA. Lucanthone seems specific in its action on termination as it does not inhibit the elongation process on the chromatin. Among various DNA-binding drugs tested only lucanthone and proflavine are found to cause repression of the termination. The data obtained suggest that the reduced synthesis of rRNA in lucanthone-treated eukaryotic cells is due to lack of reinitiating RNA polymerases possibly caused by improper termination.


Evidence for the protection of specific RNA sequences in globin messenger ribonucleoprotein particles.

Purified 15 S globin mRNA-protein (mRNP) complexes obtained by EDTA dissociation of duck reticulocytes polyribosomes were digested with the calcium dependant Staphylococcus aureus nuclease (EC 3. 1. 4. 7.). 25% of the globin mRNA sequences were resistant to extensive nuclease digestion as determined by TCA precipitation of the digested 15 S particles labelled in vivo with tritiated uridine. Polyacrylamide gel electrophoresis of the RNA from nuclease digested 15 S particles showed that the protected oligoribonucleotides were distributed into two distinct size classes of 25,000 and 12,000 MW. Comparison between in vitro iodine-labelled 9 S globin mRNA extracted from Staphylococcal nuclease digested 15 S mRNP particles was carried out by fingerprinting. Mapping of T1 ribonuclease digests by high-voltage electrophoresis and homochromatography showed that specific oligoribonucleotides were protected against nuclease attack by proteins of the 15 S mRNP.


Apurinic acid endonuclease activity from mouse epidermal cells.

An endonuclease activity making single-strand breaks into depurinated and alkylated DNA has been purified 500-fold from carcinogen-transformed mouse epidermal cells. The enzyme was active only at apurinic/apyrimidinic sites, regardless of whether they were produced by heating at an acidic pH or by alkylation with the ultimate carcinogen MeSO2OMe. The enzyme did not act on native DNA nor on ultraviolet-induced pyrimidine-dimers nor on steric distortions caused by modification of DNA with the carcinogen (Ac)2ONFln. The enzyme was active in the presence of 1 mM EDTA; however, at pH 7.4 optimal conditions were: 6mM MgCl2 and 40--120 mM KCl or 10--40 mM potassium phosphate. The enzyme eluted from hydroxyapatite, phosphocellulose and heparin-cellulose between 100--250 mM potassium phosphate but did not bind to DEAE-cellulose. Using four chromatographic steps the endonuclease was obtained free of exonuclease, demethylase and DNA glycosylase activity specific for DNA bases methylated with MeSO2OMe or MeNOUr. The molecular weight was 31 000 +/- 3000 as calculated from the diffusion coefficient (8.2 x 10-7 cm2/s) and the sedimentation value (2.7 S).


Leptospirosis and acute renal failure--clinical experiences and a review of the literature.

About 50 cases of leptospirosis are diagnosed each year in the United Kingdom, with an overall mortality of 5%. Renal failure, in association with jaundice, is commonly held responsible for this figure. Over a period of 18 years, 6 cases of leptospirosis complicated by renal failure were treated at the Royal Air Force Renal Unit; there were 4 survivors. The 2 deaths occurred before the unit policy of daily haemodialysis and total parenteral nutrition, and were both from haemorrhagic complications. The authors believe that patients with leptospirosis and progressive renal impairment should be managed in renal units experienced in the management of the hypercatabolic patient, and that this should improve their prognosis.


[The role of anaesthesiology in intensive care (author's transl)].

The German Society of Anaesthesia and Resuscitation was founded in 1953. The change of name to "German Society of Anaesthesia and Intensive Care" in 1977 reflects the development that this specialty has undergone since 1953; it is also an indication of the claim of anaesthesia to play a part in the care of the critically ill surgical patient. To the questions: what is the basis for this claim, what can anaesthesia contribute towards the care of these cases, where is the dividing line between anaesthesia and the other disciplines concerned in intensive care, what effect has intensive care work on the training of the anaesthetist, the answers are as follows: the concern of the anaesthetist is the care of the patient whose vital functions are impaired by surgery, anaesthesia or disease; he has therefore acquired techniques and means to maintain and assist these vital functions. His work in the intensive care ward is thus often no more than a continuation of the work he is doing in the operating theatre. This does not mean that he should replace the clinician of the traditional specialties working in the intensive care unit; rather that he should function as a co-ordinator as regards the type and course of treatment and nursing. For the anaesthetist there is the advantage that he can enlarge and consolidate the skill and knowledge acquired in the operating theatre, deepen his understanding of pathophysiological conditions and gain experience and assurance in evaluation of a variety of clinical situations. By becoming competent in diverse fields (at a time when the general trend is for ever more specialization) he will contribute towards raising the status of the anaesthetist who is still apt to be regarded as merely a technician.


[Physiological and pathological aspects of the immune reactions (author's transl)].

The basic principles of modern immunology are reviewed. In analogy to the nervous defence mechanism of the body the immune reactions are divided into a "specific" afferent, "unspecific" efferent and central regulatory part. The old conception of the "lock and key" relation between antigen and antibody is re-interpreted in terms of molecular chemistry. The dual aspects of the immune response is interpreted as part of an over-all network within which the humoral and cellular defence systems are organized to act in concert. Allergy is considered to be solely a special type of immune reaction; while its disease-producing effects are undisputed its physiological significance is still obscure. The immune mechanism involved in specific densitization is discussed in detail.


[Oral desensitization in childhood (author's transl)].

1) There is some evidence that orally administered allergens are absorbed. 2) 75% of the children considered oral desensitization to be effective. 3) As judged by bronchial flow resistance after provocation, oral and subcutaneous desensitization appear to be equally effective in reducing bronchial hypersensitivity. The reduction in hypersensitivity after oral desensitization was of the same magnitude as that induced by 1 capsule of DNCG. Reduced bronchial hypersensitivity was also observed in children who had received sympatomatic anti-asthma treatment over periods of 1-3 years.


Multiple discrete sites for premature RNA chain termination late in adenovirus-2 infection: enhancement by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole.

Discrete-sized short RNA chains that contain the distinctive oligonucleotides, including the 5'-capped oligonucleotide, characteristic of the first 600 nucleotides of the adenovirus type 2 (Ad-2) large, late, rightward-reading transcriptional unit (16.4-99) accumulate in Ad-2-infected HeLa cells. In the presence of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole the accumulation of these chains is enhanced, as is the accumulation of short chains from a neighbouring rightward-reading transcriptional unit (3.0-10.7). These short chains appear to represent prematurely terminated transcripts. Late in infection there is a marked increase in RNA synthesis, including that of prematurely terminated short chains, from the large late transcriptional unit. This suggests that the increase in transcription and mRNA production from this region late in infection is not due to reduced "attenuation" of RNA synthesis.


[Content and dynamics of sulfhydryl compounds in the blood during treatment of diabetes mellitus].

The results of the study of the level of sulfhydryl groups in the whole blood and serum of patients suffering from diabetes mellitus are presented. A total of 170 patients with diabetes mellitus aged from 16 to 70 years were investigated. A severe form of the disease was revealed in 31.2% of the patients, moderately severe in 50.0%, and a mild form--in 18.8%. A significant sulfhydryl groups deficiency (P less than 0.005) was displayed by diabetic patients. The lowest content was found in patients with a severe form of the disease and with ketoacidosis. The existing methods of diabetics treatment failed to completely restore the level of sulfhydril groups. Other additional therapeutic methods are necessary for complete compensation.


Mechanism of penicillin action: penicillin and substrate bind covalently to the same active site serine in two bacterial D-alanine carboxypeptidases.

It has been hypothesized that penicillin acts as a structural analog of the acyl-D-alanyl-D-alanine terminus of nascent bacterial cell wall and that it consequently binds to and acylates the active site of the enzyme(s) that crosslinks the cell wall to form an inactive penicilloyl enzyme [Tipper, D.J. & Strominger, J.L. (1965) Proc. Natl. Acad. Sci. USA 64, 1133-1138]. This study directly proves that penicillin acylates the active site of two penicillin-sensitive enzymes, D-alanine carboxypeptidases from Bacillus stearothermophilus and Bacillus subtilis. Active site peptides were generated by chemical or enzymatic cleavage of these carboxypeptidases after covalently labeling with [14C]penicillin G or after trapping an acyl-enzyme intermediate derived from the depsipeptide substrate. [14C]diacetyl-L-lysyl-D-alanyl-D-lactate. The amino acid sequences of the penicillin- and substrate-labeled peptides were identical. Both penicillin and substrate were covalently bound via an ester linkage to the same active site residue, a serine at position 36 of the B. stearothermophilus carboxypeptidase and the corresponding serine in the B. subtilis carboxypeptidase. The two D-alanine carboxypeptidases showed significant homology around the active site. Moreover, homology between these two enzymes and four beta-lactamases of known sequence suggests that these two groups of enzymes are evolutionally related.


Chromosomal assignment of the mouse kappa light chain genes.

Mouse-hamster somatic cell hybrids containing a variable number of mouse chromosomes have been used in experiments to determine which mouse chromosome carries the immunoglobulin kappa light chain genes. It has been shown by nucleic acid hybridization that the kappa constant gene and the genes for at least one variable region subgroup are on mouse chromosome 6. This somatic cell genetic mapping procedure appears to be general and can be applied to any expressed or silent gene for which an appropriate nucleic acid probe exists.


Keratin cytoskeletons in epithelial cells of internal organs.

An antiserum against human epidermal keratins was used to detect keratins in frozen sections of various rabbit and human tissues by indirect immunofluorescence. Strong staining was observed in all stratified squamous epithelia (epidermis, cornea, conjunctiva, tongue, esophagus, vagina, and anus), in epidermal appendages (hair follicle, sebaceous gland, ductal and myoepithelial cells of sweat glands), as well as in Hassall's corpuscles of the thymus, indicating that all contain abundant keratins. No staining by the antiserum was observed in fibroblasts, muscle of any type, cartilage, blood vessel, nerve tissue, iris or lens epithelium, or the glomerular or tubular cells of the kidney. In contrast, the antiserum stained the cells of most epithelia of the intestinal tract, urinary tract (urethra, bladder, ureter, collecting ducts of kidney), female genital tract (cervix, cervical glands, uterus, and oviduct), and respiratory tract (trachea and bronchi). Epithelial cells of the fine ductal system in the pancreas and submaxillary gland also stained well. When primary cultures of epithelial cells derived from bladder, intestine, kidney, and trachea were grown on glass coverslips and stained with anti-keratin, fiber networks similar to those of cultured keratinocytes were observed. These results show that keratins constitute a cytoskeleton in epithelial cells of diverse morphology and embryological origin. The stability of keratin filaments probably confers the structural strength necessary for cells covering a free surface. Keratin staining can be used to obtain information about the origin of cell lines.


Two processing steps in maturation of vitellogenin polypeptides in Drosophila melanogaster.

Synthesis of the three vitellogenin polypeptides (molecular weights of 44,000, 45,000, and 46,000) of Drosophila melanogaster has been analyzed in vivo and in a cell-free system. After labeling periods in vivo, the three vitellogenin polypeptides were made as the principal synthetic products of the female fat body. During a short (0.5 min) labeling period, they were identified as discrete species on two-dimensional gels. Two of the polypeptides have molecular weights of 45,000 and a third has a molecular weight of 44,000. After longer labeling periods (5-45 min) the three mature vitellogenins appeared. Both immunoprecipitation and peptide mapping confirmed that the species labeled at 0.5 min are immature forms of the vitellogenin polypeptides. In vitro translation of poly(A)-RNA from female fat body indicated another processing step in vitellogenin synthesis. Three polypeptides were obtained that were identified as precursors of the vitellogenins on the basis of immunoprecipitation and peptide mapping. Two of the translation products have a molecular weight of 46,000 and the third has a molecular weight of 45,000. Because the vitellogenins are secreted proteins, we interpret the higher molecular weight of the in vitro translation products as being due to signal peptides.


Hemoglobin ontogeny during normal mouse fetal development.

Pure populations of large, nucleated erythrocytes derived from yolk sac blood islands were obtained during normal fetal mouse development. Embryonic hemoglobins were present in these cells early in gestation. Later in gestation, an increasing amount of adults hemoglobin was also synthesized and accumulated in this population of primitive nucleated erythrocytes, as demonstrated by both biochemical and immunocytochemical techniques.


Structural evidence for independent joining region gene in immunoglobulin heavy chains from anti-galactan myeloma proteins and its potential role in generating diversity in complementarity-determining regions.

We have determined the variable region sequences of four heavy chains from beta(1-6)D-galactan-binding myeloma proteins. Two of these proteins are identical to position 100 which is located in the third complementarity-determining region (CDR-3). The remaining two differ at a total of 8 positions over the first 100 amino acids, and all of the differences can be explained by single-base mutations at the DNA level. When an assessment is made of the protein segment following CDR-3, which has been termed "J segment" or "FR4," a completely different pattern of variation is observed. The J segments from the four proteins can be divided into two sets. Members of each set share a series of linked amino acids not found in members of the alternative set. The two proteins identical to position 100 have J segments from the two different sets, suggesting that recombination has occurred between V and J genes. An examination of the CDR-3 sequences from the four heavy chains reveals substitutions at positions 100 and 105. Gly is found at 100 in two of the proteins and His in the remaining two. In the two proteins with Gly-100, the following J sequence is limited to one of the two sets of J segments defined by linked amino acids. Similarly, the two heavy chains with His-100 have J segments from the second set. Thus, at the protein level an apparent association is seen between CDR-3 and J segment. If CDR-3 should be found linked to J segment at the DNA level, a new mechanism would be introduced for increasing antibody diversity by recombining various CDR-3 plus J genes with genes coding for the remainder of the variable region. Alternatively, if CDR-3 were coded for by the V gene, then the recombination of V with J may provide an opportunity to introduce mutations in CDR-3. In this case the linkage of amino acids in CDR-3 and the J segments would suggest that recognition signals are used such that certain V genes only pair with a given J gene.


Immunosuppression by a mouse tumor resembles antigenic competition.

The intraperitoneal injection of gamma-radiated, UV-radiated, or unradiated P-815 tumor cells into syngeneic or allogeneic mice suppressed the immune response to a subsequent intraperitoneal injection of sheep erythrocytes in a manner similar to the suppression caused by the injection of manner similar to the suppression caused by the injection of horse erythrocytes and termed antigenic competition. In both cases, the greatest suppression occurred when the sheep erythrocytes were injected at the same site (intraperitoneal) as the tumor or antigen several days after the tumor or antigen and in a dose of 10(8) erythrocytes or less.


Amino acid sequence of a mouse immunoglobulin mu chain.

The complete amino acid sequence of the mouse mu chain from the BALB/c myeloma tumor MOPC 104E is reported. The C mu region contains four consecutive homology regions of approximately 110 residues and a COOH-terminal region of 19 residues. A comparison of this mu chain from mouse with a complete mu sequence from human (Ou) and a partial mu chain sequence from dog (Moo) reveals a striking gradient of increasing homology from the NH2-terminal to the COOH-terminal portion of these mu chains, with the former being the least and the latter the most highly conserved. Four of the five sites of carbohydrate attachment appear to be at identical residue positions when the constant regions of the mouse and human mu chains are compared. The mu chain of MOPC 104E has a carbohydrate moiety attached in the second hypervariable region. This is particularly interesting in view of the fact that MOPC 104E binds alpha-(1 leads to 3)-dextran, a simple carbohydrate. The structural and functional constraints imposed by these comparative sequence analyses are discussed.


Fetal and adult albumins are indistinguishable by immunological and physicochemical criteria.

The existence of a functionally immature fetal albumin has been postulated to explain the reduced ability of newborn plasma to bind bilirubin and various drugs. In support of this, cord and adult albumin, isolated by a simple salting-out technique, were reported to differ in electrophoretic and chromatographic properties and in their resistance to alkali and proteolytic enzymes. However, the interpretation of these findings has since been questioned. To resolve this controversy, we have purified to homogeneity human serum albumins from pooled umbilical cord and adult donor plasma. The two albumins were compared and found to be indistinguishable by polyacrylamide gel electrophoresis with and without sodium dodecyl sulfate, as well as by immunoelectrophoresis and double immunodiffusion using specific antibodies against both albumins. Furthermore, the amino acid compositions, the aminoterminal sequence (Asp-Ala-His-Lys-Ser-Glu-Val-Ala-), the carboxy terminus (Leu), and the peptide fingerprints were identical in the two albumins. No significant differences were found by circular dichroism in the ultraviolet (200-350 nm). Binding studies with bilirubin showed association constants of 3.7 +/- 0.7 x 10(7) M(-1) for cord and 2.9 +/- 0.3 x 10(7) M(-1) for adult albumin, respectively. The circular dichroic spectra of 1:1 bilirubin.albumin complexes showed considerable variation between the batches but were not significantly different. The only difference was found in the fluorescence spectra of the bilirubin.albumin complexes, in which complexes with adult albumin showed only 75% of the relative fluorescence exhibited with cord albumin. The combined results nevertheless strongly indicate that fetal and adult albumins are very similar, if not identical.


Partial purification of Rho (D) antigen from Rh positive and negative erythrocytes.

A rapid method is described for partial purification of Rho(D) antigen from sodium deoxycholate-solubilized erythrocyte membranes by affinity chromatography on a column coupled with anti-Rho(D) IgG. The Rho(D) antigen is a low molecular weight membrane protein that comigrates with the lipid zone of erythrocytes during sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Similar quantities of Rho(D) antigen were present in Rh positive and negative erythrocytes. However, in the latter erythrocytes the antigen may not be exposed to the external cell surface, explaining why these cells are not agglutinated by anti-Rho(D) antiserum. LW antigen was also present in the fraction containing Rho(D) antigen. The genetic implications of these findings are discussed.


Roots of neglect of the long-term mentally ill.

A pattern of neglect of the severely mentally ill, then outrage and movements for reform, followed again by a lapse into neglect has been characteristic of the mental health professions and society generally. This article explores the possibility that neglect of the mentally ill may be rooted in professionals' dissatisfaction with meeting chronic dependency needs, a moral disapproval of dependency and passivity, a distaste for the lower social classes, and an inclination, like that in the larger society, to exclude the mentally ill. The discussion then turns to the problem of the overselling of rehabilitation and the observation that despite the powerful dependency needs and limited tolerance for stress of the mentally disabled, when attention is finally turned to them, neglect often gives way to unrealistic expectations of rehabilitation. The paper concludes with recommendations for alleviating these problems.


Tryptophan-free diet: effects on the acoustic startle reflex in rats.

In Experiment 1, body weights of rats fed a powdered tryptophan-free (TF) diet decreased monotonically during a 13-day period. Control animals fed the same diet supplemented with 0.5% L-tryptophan gained weight. The groups did not differ significantly in acoustic startle amplitude measured at 2, 4, 6, 7, 9, 11, and 13 days despite a 28% decrease in whole-brain serotonin in the TF rats. In Experiment 2, daily intubation of rats with a syrup form of each diet maintained the two groups' body weights at comparable levels. TF diet intubation decreased whole-brain serotonin by 64% and produced significantly elevated startle amplitudes, which returned to control levels when 0.5% L-tryptophan was added to the diet. Changes in whole-brain serotonin level preceded changes in startle amplitude by several days. In Experiment 3, acute injections of 125 mg/kg L-tryptophan significantly reduced the startle amplitude of TF diet intubated rats and significantly raised their brain serotonin levels. The results show that acoustic startle reflex is increased by a TF diet, provided the animals receive adequate nourishment, and suggest that this facilitation may result from depletion of brain serotonin.


Dopaminergic supersensitivity: influence of dopamine agonists, cholinergics, anticholinergics, and drugs used for the treatment of tardive dyskinesia.

Single and repeated administration of neuroleptics induce supersensitivity to dopamine agonists like apomorphine and methylphenidate. The degree of this supersensitivity depends on the period of the preceding administration of the neuroleptic. In the development phase additional administration of apomorphine can reverse the hyperdopaminergic behaviour, whereas addition of cholinergic/anticholinergic treatment does not modify the enhanced receptor response. In the supersensitivity phase additional treatment with deanol does not modify the supersensitivity. Pheobarbital, diazepam, and muscimol increase and cis (Z)-flupenthixol decreases the supersensitivity. It is concluded that supersensitivity induced by neuroleptics is time-dependent and that it can be prevented by additional treatment with DA-agonists but not by cholinergic/anticholinergic treatment. In the supersensitivity phase, the syndrome is suppressed by dopamine antagonists but enhanced by GABA-agonists, benzodiazepine and phenobarbital.


Comparative behavioral effects of clorgyline and pargyline in man: a preliminary evaluation.

The antidepressant and other behavioral effects of clorgyline, a preferential inhibitor of monoamine oxidase (MAO) type A, were compared with those of pargyline, a preferential inhibitor of MAO type B, in 16 depressed patients. In a subgroup of more severely depressed patients, clorgyline treatment for 4 weeks resulted in significant improvement on both observer-rated and self-rated scales, while minimal changes occurred during pargyline treatment. Similarly, in a crossover study that included 8 patients examined with multiple scales, clorgyline had generally greater antidepressant and antianxiety effects than did pargyline, although pargyline had some activating effects and also tended to produce more side effects. MAO type A inhibition may be more important than MAO type B inhibition for antidepressant efficacy.


Selectivity of clorgyline and pargyline as inhibitors of monoamine oxidases A and B in vivo in man.

During 4 weeks of treatment with clorgyline, a selective MAO-A inhibitor, platelet monoamine oxidase (MAO) activity was unchanged. During a similar 4-week crossover treatment period with pargyline, a selective MAO-B inhibitor, platelet MAO activity was essentially completely inhibited in the same individuals. The differential effects of the two drugs on platelet MAO, which consists exclusively of the MAO-B form, suggests that the in vitro selectivity of clorgyline, and possibly of pargyline, on MAO-A and MAO-B may be maintained in vivo during long-term administration in man. Reductions in blood pressure, heart rate, and plasma amine oxidase activity were generally similar in magnitude during treatment with both drugs, however, suggesting that either these effects are nonspecific consequences of both MAO-A and MAO-B inhibition, or that pargyline also inhibited MAO-A activity.


Plasma levels of d-amphetamine in hyperactive children. Serial behavior and motor responses.

Amphetamine has been clearly documented to be an efficacious treatment for hyperactive children. The pharmacokinetics of amphetamine have been studied in adults, but not in children. Sixteen male children who scored greater than 2SD from norms on Factors I and IV of Conner's Teacher Rating Scale and who were not excluded for reasons to do with medical or psychiatric conditions, intelligence, or age, had a plasma d-amphetamine apparent elimination half-life of 6.8 +/- 0.5h. Peak plasma level occurred between 3 and 4h (62.7 +/- 3.8 and 65.9 +/- 3.6 ng/ml, respectively). Six of these children had a repeat study and there were no significant differences within subject in apparent elimination half-lives and attained peak blood levels. The variation in plasma levels was greater during absorption than during elimination. Both behavioral and motor activity responses as analyzed by differences between amphetamine and placebo days (by paired t-tests) indicate significant responses between hours 1--4; however, these responses do not correlate with plasma amphetamine levels; they occur during the absorption phase. The decreased response to later similar plasma levels of d-amphetamine may be related to depletion of catecholamine stores, to replacement by a 'false neurotransmitter' metabolite of amphetamine, or to alteration in receptor sensitivity.


Joint effects of ethanol and caffeine on schedule-controlled responding in the pigeon.

Interactions between ethanol and caffeine were studied in pigeons keypecking under a multiple fixed ratio 30 fixed interval 5-min schedule of food presentation. When ethanol was administered alone, rates of responding under both components of the multiple schedule were generally decreased in a dose-related manner. Caffeine alone either decreased or had no effect on rates of responding under both the fixed ratio and fixed interval components. When caffeine and ethanol were combined, doses of caffeine which did not decrease rates of responding when given alone attenuated the rate-decreasing effects of ethanol.


Effects of LSD-25 on avoidance behavior and locomotor activity in mice.

C57BL/6(C57) mice were tested in a shuttle box under the influence of LSD-25 in two sets of experiments. In the first set, the pretrial administrations of LSD (0.05, 0.1, and 0.2 mg/kg) were followed by dose-related performance improvements. In the second set, the posttrial administration of LSD (0.2 mg/kg) immediately after each experimental session improved the performances of the mice. No effect was evident when the hallucinogen was injected 2 h after training, thus showing that LSD improved the memory processes of the C57 mice in these experimental conditions. Dose-related activity depressant effects were evident in a third set of experiments, carried out in a toggle-floor box.


Every-other-day acetylmethadol disturbs circadian cycles of human motility.

1-Alpha-acetylmethadol (LAAM) maintenance treatment has been proposed as a favorable alternative to methadone maintenance. With an unobtrusive actometer we recorded two successive 24-h cycles of spontaneous motor activity from 12 patients receiving LAAM every other day, and from five receiving methadone every day. LAAM patients were about 50% more active on days of drug administration than on no-dose days (P less than 0.001). There were no significant day-to-day differences in motility of methadone patients. LAAM administered every other day may significantly modify the human circadian rhythm of spontaneous motility; further research is thus needed before this treatment is widely adopted.


Evidence of central cholinergic mechanisms in the appearance of affective aggressive behaviour: dissociation of aggression from autonomic and motor phenomena.

Carbachol, muscarine, eserine and neostigmine injected into the cerebral ventricles of conscious cats evoked emotional behaviour with aggression, autonomic and motor phenomena as well as clonic-tonic convulsions. The main and the most impressive feature of the gross behavioural effects of intraventricular carbachol, muscarine, eserine and neostigmine in conscious cats was the affective type of aggression. However, neostigmine produced aggressive behaviour only in about one-quarter of the experiments. After intraventricular hemicholinium-3 and triethylcholine carbachol, muscarine, eserine and neostigmine elicited autonomic and motor phenomena. In these cats cholinomimetics and anticholinesterases evoked only slight hissing and snarling. Choline administered into the cerebral ventricles of hemicholinium-3 and triethylcholine-treated cats restored the emotional behaviour with aggression, autonomic and motor phenomena as well as clonic-tonic convulsions to intraventricular carbachol, muscarine, eserine and neostigmine. The restored gross behavioural changes to eserine were almost of the same intensity, while those to carbachol and muscarine were of lesser intensity than in control cats. From these experiments it is concluded that cholinergic neurones are involved in the appearance of the affective type of aggression resulting from intraventricular carbachol, muscarine, eserine and neostigmine.


Failure of apomorphine to induce dopamine receptor hypersensitivity.

Apomorphine, a direct dopamine agonist, failed to induce the so called dopamine receptor supersensitivity. Furthermore, a review of the evidence strongly suggests that the mechanisms involved in this phenomenon are not purely dopaminergic. This phenomenon is more complex than one of simple changes in the sensitivity or number of a particular type of receptor. Also sexual differences were observed and the literature suggest an involvement of serotoninergic mechanisms in sterotyped behavior.


Mood alterations during deanol therapy.

An imbalance between central cholinergic and adrenergic influences may affect mood disorders. Of 38 patients taking high doses of deanol, a putative acetylcholine precursor, eight developed changes in mood: five became depressed and three became hypomanic. A predisposition is suggested as seven of these eight patients had histories of affective symptoms. There was no relationship between the changes in dyskinesias and mood. These observations have both practical and heuristic implications for the management of patients and for further research into the pharmacology of affective disorders and deanol.


Naloxone enhancement of DMT and LSD-25 induced suppression of food-rewarded bar pressing behavior in the rat.

The narcotic antagonist naloxone was tested to determine its possible interaction with N,N-dimethyltryptamine (DMT) and lysergic acid diethylamide-25 (LSD) in adult male Holtzman rats trained to press a bar on a fixed-ratio four schedule (FR4), i.e., every fourth press earned a reward of 0.01 ml sugar sweetened milk. LSD (0.1 mg/kg) or increasing doses of DMT (1.0, 3.2, and 10.0 mg/kg) were administered i.p. to disrupt food-rewarded fixed ratio bar pressing in a dose related fashion. Pretreatment (5--10 min) with behaviorally ineffective doses of naloxone (1.0--5.6 mg/kg) dramatically enhanced the effects of DMT and LSD. The content of DMT in the brain and liver of rats injected with DMT alone (10 mg/kg) and with a 5 min pretreatment of naloxone (3.2 mg/kg) was determined by radiochemical analysis at 30 and 90 min after 14C-DMT injection. There was no significant difference for either brain or liver 14C-DMT levels when control DMT rats were compared with the naloxone pretreated rats. These results seem to rule out interference by naloxone with the metabolism of DMT as a mechanism of the observed behavioral potentiation.


Interaction of alcohol and reward in an achievement situation.

Effects of psychological stress on acute alcohol intoxication following intake of 2 ml whisky/kg body weight were examined in 12 healthy subjects. Each subject performed a 45-min psychomotor task under four conditions, two of which increased achievement stress by promising the subject a monetary reward for rapid and accurate performance. The conditions were (a) task only, (b) task + reward, (c) task + alcohol, and (d) task + reward + alcohol. In condition (b) reward improved performance and heightened both physiological and subjective arousal, and in condition (c) alcohol impaired performance, lowered subjective arousal, and increased physiological arousal. In condition (d) the reward counteracted the depressant effects of alcohol on performance and mood, whereas an additive, arousing effect was obtained in all physiological variables, i.e., catecholamine and cortisol excretion and heart rate.


Paradoxical effect of amphetamine in an endogenous model of the hyperkinetic syndrome in a hybrid dog: correlation with amphetamine and p-hydroxyamphetamine blood levels.

A telomian-beagle hybrid has been studied as a possible model for the hyperkinetic syndrome in children. Behavior tests showed that hybrids, like children, exhibit hyperactivity, impulsiveness, and impaired learning. Two groups of hybrid could be differentiated; the behaviour of one improved after amphetamine (responders) while that of the other did not (nonresponders). Moreover hybrids were less responsive than beagles to other effects of amphetamine such as stereotyped behaviour and hyperthermia. Measurement of blood levels of amphetamine and its active metabolite p-hydroxyamphetamine (pOA) showed that hybrids form less pOA. We propose that the lesser response of hybrids to toxic effects of amphetamine is due to this difference in amphetamine metabolism. Responders showed higher peak blood levels of amphetamine than nonresponders and their improvement on amphetamine correlated with blood levels of amphetamine. Therefore high levels of amphetamine appear to be necessary for its 'paradoxical' effect in this model. This suggests that amphetamine acts by activating both noradrenergic and dopaminergic neuronal systems in the CNS.


EEG effects of physostigmine and choline chloride in humans.

Seventeen normal volunteers received either 0.5 mg, 1.5 mg, or 2.5 mg physostigmine i.v. in a placebo-drug-placebo single-blind design. EEG was recorded simultaneously and analyzed by computerized spectral analysis. Eleven healthy elderly volunteers (mean age = 69.1 years) with mild memory impairment were treated with placebo, followed by oral choline chloride (either 8 g/day for 3 weeks, or 16 g/day for 1 week), and then, again, placebo. Recordings of spontaneous EEG and EEG event-related potentials (contingent negative variation) were obtained during both placebo and choline treatments. The larger doses of physostigmine produced an increase in low frequency activity and a slowing of the peak alpha frequency. Oral choline chloride had no effect on the EEG as measured by spectral analysis, but appears to have differential effects on contingent negative variation (CNV) amplitude and reaction time, depending upon the initial CNV amplitude.


Naloxone antagonizes theophylline-induced potentiation of morphine inhibition of a nociceptive reaction in rats.

In the rat, theophylline has been shown to potentiate the effect of morphine on the threshold for vocalisation after withdrawal of stimulation. This response to painful stimulation is considered to be integrated at the level of the thalamus-hypothalamus-rhinencephalon. Naloxone antagonized the effect of the combined treatment with morphine and theophylline, suggesting pharmacological specificity for morphine. Moreover, the theophylline-induced enhancement of this pharmacological response to morphine was attenuated after pimozide pretreatment, indicating an underlying dopaminergic mechanism.


Sources of variation in locomotor activity and stereotypy in rats treated with d-amphetamine.

Rats injected with doses of d-amphetamine 0--5.0 mg/kg were observed continuously in either an enclosed Y-maze or on an elevated Y-shaped platform. Patterns of increased walking and stereotypy were unaffected by the type of apparatus, but rearing remained totally suppressed at all dose levels on the elevated platform. In the second experiment, groups of rats where given single short tests in the enclosed Y-maze, which was novel to them. The stimulant actions of d-amphetamine on locomotion were obscured by high baseline levels of motor activity induced by the novel environment. Continuous measurements of habituated rats may provide a more sensitive means of evaluating stimulant actions of drugs in screening tests. The observed changes in patterns of onset and offset of increased locomotion and of stereotypy were consistent with the view that these types of behaviour are, to some extent, independently, mediated.


Effects of ethyl alcohol on development and social behaviour in the offspring of laboratory mice.

Behavioural and developmental effects of exposure to a low level of ethyl alcohol from conception to adulthood have been examined in mice. A 5% solution of alcohol in the drinking fluid of male and female adults did not impair fertility. The offspring of treated mice were significantly lighter at birth than their controls and remained so throughout their life span. No congenital malformations were observed. Behaviour of the offspring 3--4 weeks of age and in adulthood was examined by ethological analysis of encounters between alcohol-treated and control mice of the same sex. In male and female juvenile mice receiving 5% alcohol, the frequency and duration of social investigation were significantly lower than those of control partners and the duration of non-social behaviour was raised. Individual elements of 'investigate' and 'sniff' were significantly reduced in frequency. In alcohol-treated adults, the only behavioural difference from controls was an increased frequency of flight elements occurring in males. It is suggested that long-term exposure to alcohol may lead to behavioural adaptation.


Feeding parameters with two food textures after chlordiazepoxide administration, alone or in combination with d-amphetamine or fenfluramine.

Chlordiazepoxide (5.0, 10.0 mg/kg) reduced the rate of eating and extended the duration of feeding in a 10 min feeding test. It also reduced the latency to feed. Both fenfluramine (1.0 mg/kg) and d-amphetamine (0.25 mg/kg) acted to reduce food intake, but by differing mechanisms. Fenfluramine reduced eating rate without affecting eating duration, whilst d-amphetamine reduced eating duration without reducing eating rate. The effects of chlordiazepoxide on feeding parameters were generally additive with those of either d-amphetamine or fenfluramine, whenever chlordiazepoxide was given in combination with one of the anorectic drugs. Food texture affected feeding behaviour; rats ate standard diet in pellet form faster than powdered food, although they spent longer eating the powdered food. Textural differences did not significantly interact with the changes in feeding responses induced by the 3 drugs, except that latency to eat after either d-amphetamine or fenfluramine injection, when pellets were available, was significantly prolonged. Characterising drug effects on feeding in terms of a 2-dimensional matrix of eating rate and duration is recommended, rather than relying solely on amount of food consumption as the measure of drug effects.


Effects of alcohol, instructions, and consumption rate on affect and physiological sensations.

Sixty-four male normal drinkers participated in a study designed to assess the effects of alcohol, instructions that one has consumed alcohol, and rate of alcohol consumption on self-reports of affect and physiological sensations. Subjects were instructed that they would be consuming either an alcoholic or a nonalcoholic beverage, were actually administered either an alcoholic or a nonalcoholic beverage, and consumed their beverages at either a slow or rapid rate. The results showed that consumption of a moderate dose of alcohol induced positive affect and produced a variety of changes in physiological sensations. Instructions and consumption rate also selectively influenced some affects and sensations. These results suggest the need for controlling instructions and consumption rate in future research on alcohol's effects on affect and physiological sensations.


Brain tryptophan metabolism in schizophrenia: a post mortem study of metabolites of the serotonin and kynurenine pathways in schizophrenic and control subjects.

Serotonin (5HT), its chief metabolite 5-hydroxyindoleacetic acid (5 HIAA), its precursor tryptophan, and kynurenine, another metabolite of tryptophan, have been measured in post mortem human brain samples. Concentrations of these metabolites were not found to be significantly different in putamen, hippocampus or temporal cortex from 23 normal subjects compared with 15 subjects in whom a diagnosis of schizophrenia could be restrospectively confirmed. The results have been analysed with respect to cause of death, medication and post mortem changes. Post mortem increases in tryptophan and kynurenine were observed. Some interrelationships between the variables measured within and between the different areas studied are discussed. It is concluded that there is no evidence for a generalised deficit of 5HT in the brain in schizophrenia, nor for gross changes in turnover along the serotonin or kynurenine pathways of tryptophan metabolism in brain.


The central action of pizotifen.

The central action of the potential antidepressant drug pizotifen (Sandomigran) was studied in mice, rats and rabbits. Pizotifen in doses up to 10 mg/kg i.p. was ineffective in classic tests for antidepressant activity. It neither antagonized the effects of reserpine in rats (hypothermia, ptosis) nor potentiated the effects of amphetamine (in mice and rats), nialamide or L-dopa (in mice) on locomotor activity. However, its antidepressant activitiy was found in the 'despair test' in rats. On the other hand, pizotifen inhibited the head twitch reaction induced by L-5-hydroxytryptophan in mice (ED50 = 0.009 mg/kg, i.p.) and by 5-methoxytryptamine (+ tranylcypromine) in rats (ED50 = 0.45 mg/kg, i.p.). It also antagonized tryptamine-induced clonic convulsions of fore-paws in rats (ED50 = 0.35 mg/kg, i.p.), and in doses of 5--10 mg/kg s.c. inhibited hyperthermia produced by LSD in rabbits. Finally, pizotifen (0.1--0.3 mg/kg, i.v.) inhibited or abolished LSD- or quipazine-induced stimulation of the hind limb flexor reflex of spinal rats; the above effect was not due to noradrenolytic action of the drug. These results suggest that pizotifen strongly blocks the central postsynaptic serotonin receptors.


Behavioral effects produced by long-term administration of a neuroleptic drug (flupenthixol) upon social interaction in a group of eight rats.

The behavioral effects produced by chronic treatment with alpha-flupenthixol decanoate followed by a 3-month pause upon social interaction in a group of eight rats were studied. alpha-Flupenthixol decanoate induced total disruption of two of the group formations studied, i.e., three or more in a group outside a corner and three or more following (running in a row)--the overall behavioral change shows a general depressive effect of the drug and a change in the pattern of social interaction. The shift in balance between the behavioral categories measured appeared as a significant difference in the time spent in the various group formations. Disintegration of group coherence, as shown in the measures of the degree of isolation, appeared only in the alpha-flupenthixol decanoate-treated group. An apomorphine test, which concluded the experiment 3 months after the last alpha-flupenthixol decanoate injection, revealed a significant difference in relation to licking response between the test group and the control group. The apomorphine test reported in this paper showed effects up to 90 days after the last drug treatment.


Naloxone effects on schedule-controlled behavior in morphine-pelleted rats.

The effects of morphine pellet implantation and naloxone administration were examined in rats lever pressing under inter-response time schedules of food presentation. Subcutaneous implantation of a morphine pellet initially decreased lever-pressing rates. Tolerance to this effect developed within 3--4 days. Naloxone (0.25--1.0 mg/kg) decreased response rates in morphine-pelleted rats in a dose-dependent and time-dependent manner. All doses of naloxone severely decreased rates of lever pressing on days four to nine post-pellet. This rate-decreasing effect persisted 7--17 days for 0.25 mg/kg naloxone, 9--22 days for 0.50 mg/kg, and 13--28 days for 1.0 mg/kg. Decreases in response rate were due to an increased frequency of long pauses and not to marked shifts in the temporal patterning of those lever presses that did occur. Changes in response rate after naloxone were accompanied by body weight loss. Area values summarizing the naloxone-induced changes in response rate or body weight over time after pellet implantation increased as a function of naloxone dose. Naloxone (0.25--1.0 mg/kg) did not alter performance by placebo-pelleted rats.


Arthrosonography: gray-scale ultrasound evaluation of the shoulder.

Gray-scale ultrasound images of the shoulders of 6 rhesus monkeys were obtained before and after fluid instillation to assess the ability of ultrasound to diagnose joint disorders. The normal bony landmarks and muscular structures were shown. After the fluid was introduced, fluid collections were identified in the axillary pouch and subscapular bursa. Ultrasound is a promising new method of detecting intra-articular effusions of the shoulder.


Preliminary observations on the potential of 99mTc-sulfur colloid as a radiopharmaceutical for detection of deep vein thrombosis.

The potential usefulness of 99mTc-sulfur colloid (Tc-SC) as a radiopharmaceutical for thrombus detection was evaluated in an animal model of deep vein thrombosis. One hour after injection of Tc-SC and 24 hours after induction of thrombus formation, a mean thrombus-to-blood uptake ratio of 11.38 was obtained in 12 beagles. This ratio is high enough to allow external detection.


Radiation dose to the eyes using a "German helmet" field with the 4-MV linear accelerator.

A "German helmet" field defined by depleted uranium or Asarcola blocks was used to reduce the dose to the lens. With the uranium blocks, the lenticular dose was reduced to about 60% of the central axis dose (CAD). The Asarcola blocks reduced the lenticular dose to about 43% of the CAD. Even further reduction (15% CAD) was achieved by tilting the gantry 5 degrees or 10 degrees.


Field shaping for electron-beam radiation therapy.

A system for designing electron-beam treatment fields of any shape and size using the low-melting alloy Lipowitz's metal is described. An individualized shield is produced for each patient. The shields are designed to be mounted on any of the six cone sizes provided with the Varian Clinac 18 linear accelerator but should be adaptable to most accelerators which use cones for electron-beam collimation. Materials are reusable upon completion of treatment.


Prevention of blockage of partially obstructed coronary arteries with prostacyclin correlates with inhibition of platelet aggregation.

Coronary arteries (circumflex or left anterior descending) of anesthetized dogs were partially obstructed to approximately 5% of the normal lumen size by fitting a plastic cylinder around the vessel. Under these conditions, blood flow in the artery was not maintained but, instead, gradually declined over a few minutes until the vessel was completely blocked. Shaking the plastic obstructor restored blood flow temporarily, however, flow gradually declined again to zero. Sometimes flow was spontaneously restored by immediate increases that occurred at irregular intervals while, on other occasions, blood flow had to be restored by shaking the obstructor every time the rate declined to near zero. Intravenous infusion of prostacyclin (PGI2) at 15 to 150 ng/kg/min reversed and prevented the blockage of the coronary arteries. The efficacy of PGI2 in preventing blockage correlated with inhibition of ADP-induced platelet aggregation in platelet rich plasma prepared from blood samples withdrawn from the dogs during PGI2 infusion. Other coronary vasodilators, nitroglycerin and PGE2, that have no antiaggregatory effects, failed to prevent blockage whereas PGE1 and indomethacin, which do block aggregation, also prevented blockage of the vessels. PGI2 or its precursor, PGH2, dripped topically on the obstructed site prevented the blockage of the artery. This local effect of IGI2 could be obtained with amounts too small to cause systemic inhibition of platelet aggregation. The results show that PGI2 prevents blockage of partially obstructed coronary arteries and this effect correlates with inhibition of platelet aggregation. Furthermore, the data suggest that locally produced PGI2 may have a local antiaggregatory effect without inhibiting platelet aggregation in the general circulation.


Influence of angiotensins (I, II, & III), bradykinin and arachidonic acid on renomedullary PGE production in vitro.

Renomedullary tissue from rabbit or rat was incubated with angiotensin I, II, III, arachidonic acid, bradykinin, indomethacin and meclofenamate to study their effect on PGE2 production. Arachidonic acid and bradykinin enhanced PGE2 production significantly. Indomethacin and meclofenamate inhibited PGE2 production by more than 70%. Angiotensin I, II and III did not influence PGE2 production. These results suggest that bradykinin and arachidonic acid stimulate PGE2 production by a direct cellular action whereas the angiotensins do not.


[Early immunological aspects in rats infected by Trypanosoma cruzi. II. Soluble antigen circulation and the modifications of serum complement from animals in sucessive days of the infection (author's transl)].

A group of rats was infected by the Y strain of T. cruzi and three animals were bled daily from the 4th to the 13th days. The sera obtained each day, after being mixed, were used for dosing serum complement and for acting as antigens in the CFT with a Chagas' disease serum. The amount of circulating antigen increased gradually, reached a maximum in the 5th and 6th days and then decreased up to the 10th day; thereafter it increased attaining a new maximum in the 11th day and again decreased up to the 13th day. The dosage of the complement showed that the 50 per cent unit was about 70 x 10(-4) in the first few days of the infection, reached 130 -- 135 x 10(-4) in the 7th and 8th days, and was back again to the initial levels in the 13th day. These results suggest a relation between the circulation of antigens, the formation of antigen antibody complexes, and the fixation of the complement by such complexes.


Subsets of T lymphocytes and lymphocyte cooperation. Modulation of the immunocellular response.

Recent advances in the characterization of T cell subsets suggests that the various subsets of T cells described in mice also occur in man. These various subsets of T cells can be detected by the use of appropriated antisera, co-cultivation of purified lymphoid cell preparations and differential sensitivity to radiation. Clinical applications from these new observations are now underway and it is hopeful that they should help to achieve a better understanding of the mechanisms responsible for autoimmunity, neoplasias and the various primary and secondary immunologic deficiencies.


[Diverticula of the duodenal orifice].

The authors present a synthesis of data from the literature, as well as of particularities that have confronted them in connection with 16 observations of mucous diverticuli of duodenal windows (of which 7 were interposed and 9 were juxtaposed). After a definition of the window diverticuli, of their types and of their repercussions, clinical data are commented upon, the possibilities offered by paraclinical investigations and by the intra-operatory methods, as well as the different therapeutical procedures. In relation with the clinical manifestation the diverticuli may be latent (or asymptomatic), they may be accompanied by direct signs of stasis and inflammation, or with biliary and pancreatic signs--an expression of the unfavourable influence exerted by the diverticuli on the biliary and pancreatic transits. The choice of the therapeutical procedure depends on the type of the diverticuli, the modality of the clinical expression and the bilio-pancreatic effects determined by them. Direct interventions can be performed on juxtaposed diverticuli, although this implies considerable risk, but indirect interventions are to be preffered, in which, in relation with the particularities of the case, the biliary transit is derivated or the duodenum is excluded from the digestive pathways.


Adjuvant therapy of T1 bladder carcinoma: preliminary results of an EORTC randomized study.

This paper reports the preliminary results of an ongoing clinical trial in patients with category T1 bladder cancer who are randomized after transurethral resection to receive either thiotepa, VM-26, or no treatment. While there are no significant differences between the three treatment groups with respect to the time until first recurrence, thiotepa has significantly reduced the recurrence rate as compared to either VM-26 (P = 0.03) or no treatment (P = 0.04) among the 215 patients for whom follow-up information is currently available.


DNA single strand breaks caused by 2,2',5,5'-tetrachlorobiphenyl and its metabolites.

Polychlorinated biphenyls (PCBs) are widespread environmental pollutants which have been shown to be carcinogenic. One possible mechanism for the apparent carcinogenicity of PCBs is their metabolism to phenolic metabolites through an arene oxide intermediate, with the arene oxide that is formed being the ultimate mutagenic or carcinogenic species. The ability of a tetrachlorobiphenyl and its phenolic and arene oxide metabolites to cause single strand breaks in DNA was therefore examined. 2,2',5,5'-TCB-3,4-epoxide was more potent in causing DNA single strand breaks than either 2,2',5,5'-TCB or a mixture of 3-hydroxy and 4-hydroxy-2,2',5,5'-TCB. These results support the idea that PCB epoxide may be involved in PCB carcinogenesis.


[Minimal protein and calories parenteral route requirements in order to have a positive nitrogen balance in patients with acute diseases].

A study was conducted on a group of 30 patients with mormal nutritional conditions who required parenteral alimentation. Three groups were selected at random. They received glucose as a calorie source and nitrogen from amino acids derived from hidrolizate of natural protein. Group I received 40 Kcal/kg/day and 250 mg of nitrogen/day. Group II 30 Kcal/kg/day and 175 mg nitrogen/kg/24 hours. And group III received 20 Kcal/kg/day and 100 mg of nitrogen/kg/24 hours. The first two groups had a positive nitrogen balance and the third group had negative balance. The positive nitrogen balance of group I, was only 670 mg better than the obtained for group II. Group I received 4 gr more of nitrogen than group II. This study show that the scheme of calories and nitrogen administered to the group II was the best for the maintenance of the nutritional conditions in the patients studied.


[Typical changes of the intestinal wall due to oral stenosing processes (author's transl)].

Two different changes of the intestinal wall, which seem to be of stenotic orgin, can be observed prä-stenotically. One of these changes is represented by diverticulosis, whereas the other is the so-called ischaemic-ulcerous lesion of the mucosa. The latter accompanying disease supplies highly important preoperative information. This condition can be diagnosed practically exclusively by the roentgenologist. In many cases, stenosis makes endoscopic assessment impossible. Diverticulosis is of theoretical interest in this connection. The article goes into the possible aetiology of the changes. Two typical cases underline the importance of the diseased conditions under discussion, which are relatively rare, as is evident from a statistical evaluation of the author's case material.


[Antibacterial immunity in diphtheria. Experimental research].

A number of 700 guinea pigs were immunized by parenteral route with non-toxigenic Corynebacterium diphtheriae strains, then inoculated with various doses of homologous and heterologous toxigenic C. diphitheriae strains. The results showed that non-toxigenic C. diphtheriae strains confer a certain degree of protection when the challenge is done with homologous toxigenous strains, especially when not more than 500 million germs/ml are used for the challenge dose. This suggests that the carriage of non-toxigenic diphtheriae bacilli is a useful phenomenon for maintaining an immune balance in diphtheria in the present epidemiological context, and that their sterilization is not opportune.


[Laboratory diagnosis of group D Streptococcus].

After taxonomic listing of group D streptococci, the authors discuss the methodology of the bacteriologic diagnosis of infections produced by these bacteria, showing the way in which the pathological products are collected, the strains isolated and seeded. The strains are identified in two stages: (1) group identification by group antigen identification, resistance to oxacillin, development at +45 degrees, development on bilaesculin media; (2) species and variety identification by biochemical, physiologic and metabolic tests, by lysotyping and enterocinotyping. A description is given of the testing of sensitivity of the strain to antibiotics by determination of the minimal inhibitory concentration. The formulas of the media used for culture and identification are given.


[Rapid methods useful for determination of streptococcal groups with special reference to streptococci of groups B and D].

A study was carried out on the efficiency of certain rapid methods for the identification of streptococcal groups, especially groups B and D, methods based upon physiologic properties such as hippurate hydrolysis, production of pigment, esculin hydrolysis, tolerance to salt and bilolysis, associated with the classical tests, for instance the hemolysis type and sensitivity to bacitracin and optochin. By these tests, accessible to hospital laboratories, a number of 3083 streptococcal strains were correctly identified within 2 to 18 hours, of which 2567 group A, 31 group B, 184 group C, G, 113 group D, 155 Str. pneumoniae and 31 viridans, strains isolated from pathological products.


[Prevention of sequelae after transcutaneous radiotherapy for epitheliomas of the oral cavity (author's transl)].

Close cooperation between the radiotherapist, surgeon, and patient is necessary in order to prevent sequelae following transcutaneous radiotherapy for epitheliomas of the oral cavity. The most effective therapeutic results combined with a minimum of sequelae are obtained by the use of a good irradiation technique, close supervision, careful treatment of any oral or dental affection, prescribing simple medications only, and stopping the use of tobacco and alcohol.


Meningitis and bacteremia due to Neisseria meningitidis: clinical and laboratory findings in 69 cases from Orebro county, 1965 to 1977.

The records for 69 patients with meningococcal disease during 13 years in Orebro County were reviewed. The mean incidence during this period was 2.0/100 000 persons/year. The age group less than 1 year had the highest incidence, 15/100 000 infants/year. The mortality was 7.2% and sequelae were found in 13% of the patients. Four factors were significantly more frequent in the 7 patients with psycho-neurological sequelae: (1) Age greater than 40 years; (2) A condition prior to meningococcal disease that might have been associated with a lowered resistance; (3) Muscular hypertonia and/or marked irritability on admission; (4) Fever greater than 8 days after initiation of adequate treatment. Prodromal symptoms from the upper respiratory tract were noted in 50% of the cases. Signs and symptoms before and on admission, laboratory data and complicating events were analysed for each of 4 groups: meningitis without meningococcemia (12 patients); meningitis with meningococcemia (46): fulminant meningococcemia without meningitis (6); and benign meningococcemia (5).


2-Deoxy-D-glucose maps movement-specific nervous activity in the second visual ganglion of Drosophila.

Adult Drosophila were fed with tritium labeled deoxyglucose prior to a 5-hour period of visual stimulation. A flickering disk of light and a moving grating were presented to the left and right eyes, respectively. Autoradiography revealed enhanced labeling solely in that part of the second optic ganglion (medulla) whose visual field was stimulated by movement.


Target velocity signals of visual tracking in vermal Purkinje cells of the monkey.

Discharges of Purkinje cells were recorded from the vermis, lobules VI and VII, of a monkey trained to track a visual target. When the monkey tracked a sinusoidally oscillating target, cellular activity changes in phase with the velocity signal of the eye movement. When the monkey fixated a stationary point, almost identical modulation in activity occurred, reflecting the velocity signal of the motion of the retinal image of the target. The data suggest that the vermis participates in the control of smooth pursuit eye movements by providing the oculomotor system with the actual target velocity information which is the sum of eye velocity and retinal image velocity signals.


Evaluation of high-protein supplements in children with protein energy malnutrition.

The present study was designed to test the comparative efficacy of cow's milk, a protein, vitamin and mineral mixture (PVM) and soybean textured vegetable protein (SOMOS) as supplements to maize meal porridge in the dietary treatment of children with protein energy malnutrition (PEM). Each diet was designed to provide approximately 480 kJ/kg with 2 protein/kg from the test protein, and 1,8 g protein/kg from maize. Response to treatment was measured by loss of oedema, subsequent weight gain, rate of generation of serum albumin, and serum amino acid patterns. In 36 children studied to date the three dietary regimens all produced satisfactory rates of cure of PEM. The clinical and economic implications of these results are discussed.


Preventive social work intervention with families of children with epilepsy.

The need for preventive social work intervention with families of children with epilepsy is discussed. Issues in such counseling are identified as (a) exploring fantasies and fears about epilepsy, (b) interpreting facts about this disorder, (c) assisting parents in establishing realistic behavioral expectations and limits for the child, and (d) enabling parents to disclose information about the child's condition in such a way as to be beneficial to the child. This paper addresses itself to the needs of normal families with adjustment problems in coping with the child's epilepsy.


Sector-related variation on psychosocial dimensions in long-term care for the aged.

Quality psychosocial care was investigated among residents living in nonprofit homes, in proprietary nursing homes offering services primarily to privately paying consumers, and in homes that serve primarily Medicaid beneficiaries. A sector-related trend was found with regard to the care quality but not with regard to the importance attributed by residents to psychosocial dimensions of care.


Branched chain amino acid administration and metabolism during starvation, injury, and infection.

Branched chain amino acids were administered intragastrically in a septic-fractured rat model to determine the degree and mechanism of their protein-sparing ability. The septic injury model was first shown to produce a metabolic response characterized by hyperglycemia, reduced ketonemia and increased nitrogen loss. Branched chain amino acids were then administered either alone or as 25% or 50% (w/w) of a complete crystalline amino acid solution. L-(U-14C)-tyrosine was added to the diet to estimate protein synthesis in individual tissues. Branched chain amino acids, when given alone, spared total body nitrogen as compared with fasting by increasing the fractional synthesis of both mixed liver and muscle protein. Although the two complete amino acid mixtures produced similar nitrogen preservation and muscle synthesis in the septic animals, the crystalline amino acid diet containing 50% branched chain amino acids resulted in the greatest preservation of total liver nitrogen and the highest fractional synthetic rate. The effect of branched chain amino acids would not appear to be explained by their nitrogen content alone, and in starvation with injury and infection, increased intakes may have potential benefit. Clinical trials in starved, injured man appear to be indicated.


Evidence that the cholinergic enteropancreatic reflex may be independent of cholecystokinin release.

Studies were performed in four dogs with chronic gastric and pancreatic fistulas following intraduodenal perfusion with 10 mmole hr-1 of sodium oleate for 30 minutes. Radioimmunoassay (RIA) of plasma CCK LI was undertaken by an RIA method using labeled, desulfated CCK 8 I125 and an antiserum raised to CCK 8. The detection limit for the assay was 0.25 to 0.5 fmole and the lowest detectable plasma level was 5 to 10 fmoles ml-1. Since there was equal cross-reactivity to gastrin, a gastrin-specific assay also was employed to evaluate any changes in gastrin levels. After oleate infusion the plasma CCK increment above basal was 50 +/- 11 fmoles ml-1, with return to basal levels after 60 minutes. Administration of atropine significantly (P less than 0.01) inhibited the release of CCK in the first 20 minutes. Thereafter CCK release was not reduced. Plasma gastrin values did not change before and after oleate perfusion. Pancreatic protein output increased from 72 +/- 12 to 420 +/- 55 mg/10 min-1 after oleate administration. However, after atropinization the rise in pancreatic protein output was significantly lower (152 +/- 36 mg/10 min-1) (P less than 0.01). We have shown that, using our RIA method, there is a measurable rise in plasma CCK LI after intraduodenal oleate. After atropinization the CCK response was decreased significantly during the first 30 minutes, but was virtually unchanged during the second 30 minutes, when the fall in pancreatic protein output was most marked. We conclude that the cholinergic mechanism which plays a role in the endogenous stimulation of pancreatic protein secretion by intraduodenal oleate cannot be explained simply be decreased CCK release. This mechanism may be hormonal, distinct from secretin, or neural possibly, via activation of an enteropancreatic reflex.


The additive effect of timolol on open angle glaucoma patients on maximal medical therapy.

Thirty-one eyes of 20 glaucomatous patients on maximum medication were treated with timolol drops for a mean period of 9 months. Adequate levels of control of intraocular pressures were obtained in 21 eyes. No significant ocular or systemic side effects were noted. Timolol has an additive effect in further lowering intraocular pressures in patients being treated with a combination of carbonic anhydrase inhibitors, pilocarpine, epinephrine, and the anticholinesterases.


Interfering factors in the assay of plasminogen activators by the fibrin plate method. Occurrence of different inhibitors against tissue plasminogen activator and urokinase.

The assay of plasminogen activator activities on fibrin plates was re-evaluated with special reference to fibrinolysis inhibitors present in samples and in fibrin plates. The nature, action and stability of inhibiting material were studied in tissue with considerable differences in activator and inhibitor contents: human lung, liver and placenta. Extracts were tested for inhibitory capacity against purified human uterine tissue plasminogen activator, urokinase and plasmin of fibrin plates prepared from different grades of fibrinogen and fibrin. The tissue extracts inhibited fibrinolysis on fibrin plates to varying degrees, dependent on the sample medium, the type of fibrin plate and the kind of plasminogen activator. The influence of inhibitors in the sample and in the fibrin plate was partly abolished by the presence of 2 M KSCN in the sample. The procedure for preparing the samples as described by Astrup and Albrechtsen did not completely eliminate the inhibitory action against the added plasminogen activators. Comparison of urokinase inhibition with tissue activator inhibition by the tissue extracts as to the degree of denaturation in the Astrup and Albrechtsen procedure showed that they have much in common. Nevertheless, some differences were found which indicated the possible existence of separate urokinase and tissue activator inhibitors or of different inhibition mechanisms for these plasminogen activators.


Investigation of a valuable biochemical indicator in radiotherapy. I. Immunological tests and reticulocyte number.

Patients with different cancers were treated by 200-kV X-rays, high-energy X-rays and 60Co-gamma rays. Changes in the immunoglobulin level were observed by immunoelectrophoresis qualitatively and by immunodiffusion quantitatively. Reticulocyte count was made in smears. It was concluded that immunoelectrophoresis was only of limited value in the investigation of a biochemical indicator in radiotherapy; immunodiffusion was more promising. Slight immunosuppressive tendency and return to the control level was observed during treatment. An increase in reticulocyte number during radiotherapy seems to be a good prospect in evaluating the effectivity of the treatment.


[Lymphocyte response to phytohemagglutinin-stimulation after extended radiation therapy in Hodgkin's disease (author's transl)].

Phytohemagglutinin-stimulated DNA-synthesis of lymphocytes was measured in 35 patients with Hodgkin's disease in continuous remission 1 to 8 years after intensive high-energy radiotherapy. In comparison to a normal control group we found there was no significant difference between the values of patients in complete remission and healthy subjects. We conclude that the extremely suppressed lymphocytic reactivity as measured by DNA-synthesis during irradiation may again reach normal values one or two years after radiotherapy.


Competitive inhibition of cytotoxic T lymphocyte-target cell conjugation. A direct evaluation of membrane antigens involved in cell-mediated immunity.

A method to determine directly the antigenic similarity of target cells (TCs) involved in cytotoxic T lymphocyte (CTL)-TC interactions is described. When fluorescently labeled TC (FL-TCs) are bound (conjugated) to CTLs in the presence of antigenically similar but unlabeled TCs, the percentage of CTL-TC conjugates containing unlabeled TCs corresponds linearly to the number of unlabeled TCs in the TC population. This assay is specific, permits direct observation of individual CTLs and TCs which interact to form conjugates, can be completed within 10 min, eliminates complications attributable to CTL recycling, and the degree of competition observed fits that theoretically expected. The results of this paper provide the theoretical basis for "cold" (unlabeled) target inhibition of radioactive assays of lymphocyte-mediated cytolysis.