Influence of various 2- and 2'-substituted polyadenylic acids on murine leukemia virus reverse transcriptase. Several newly synthesized polyadenylic acid [(A)n] analogues, including poly(2-methyladenylic acid) [(m2A)n], poly(2-ethyladenylic acid) [(e2A)n], poly(2-isopropyladenylic acid) [(i-pro2A)n], poly(2-methylthioadenylic acid) [(ms2A)n], poly(2-ethylthioadenylic acid) [(e2A)n], poly(2'-fluoro-2'-deoxyadenylic acid) [(dAfl)n] and poly(2'-azido-2'-deoxyadenylic acid) [(dAz)n] have been evaluated for their effects on the RNA-directed DNA polymerase (reverse transcriptase) activity of Moloney murine leukemia virus; (m2A)n and (e2A)n did not markedly affect reverse transcriptase activity, (dAfl)n served as an efficient template for the reverse transcriptase reaction, and (i-pro2A)n, (ms2A)n, (es2A)n and (dAz)n strongly inhibited reverse transcriptase activity. (dAfl)n also served as an efficient template (Km : 0.025 micron) for the reverse transcriptase of avian myeloblastosis virus.


Induction of a plasmodial stage of Physarum without plasmalemma invaginations. Experimentally generated protoplasmic drops of Physarum show time-dependent differentiation processes, i.e. regeneration of plasmalemma, actomyosin fibrillogenesis and regeneration of the plasmalemma invagination system. According to Hatano (1970), caffeine treatment of drops results in a pinching off process of small translucent droplets in which specific effects of Ca++ on protoplasmic streaming phenomena were demonstrated. The light and electron microscopic investigation of the original drop reveal that the time-dependent differentiation processes, e.g. actomyosin fibrillogenesis, are not inhibited by caffeine. However, caffeine hinders the regeneration of the plasmalemma invaginations in the original drop (up to a drop age of 30--40 min). The experimental advantage of this stage of Physarum with full vitality, but without plasmalemma invaginations is discussed.


Properties of a basement membrane-related glycoprotein synthesized in culture by a mouse embryonal carcinoma-derived cell line. Two glycoproteins, GP-1 and GP-2, have been isolated from an extracellular membrane synthesized in cell culture by an embryonal carcinoma-derived cell line. The amino acid and carbohydrate compositions have been determined. Both proteins are rich in half-cystine residues and contain approximately 12-15% carbohydrate. Antibodies have been obtained against one of the glycoproteins, GP-2, in rabbits. The antibody reacts with basement membranes from adult mouse and human kidney glomeruli and tubules, and all basement membranes tested from mouse embryonic tissues. The molecular properties of GP-2 are superficially similar to LETS protein; however, immunological and other criteria show that they are distinct proteins. The presence of LETS protein and GP-2 in basement membranes suggests that there are subtle interactions which are important in adhesion of epithelial cells to basement membranes.


In vitro synthesis of a 9 kbp terminally redundant DNA carrying the infectivity of Moloney murine leukemia virus. Detergent-disrupted virions of Moloney murine leukemia virus synthesize a 9 kbp double-stranded infectious DNA. It contains mainly full-length, single-stranded DNA, and its infectivity and size are insensitive to digestion by the single-strand-specific S1 nuclease. Analysis of fragmentation of the DNA using restriction endonucleases has shown that it is indistinguishable from the linear double-stranded DNA synthesized in infected cells. On the basis of the positions of the cleavage sites for a number of enzymes, the 9 kbp DNA has a 575 base direct terminal repetition. It is longer than the viral RNA at both ends, evidently due to repetitive copying of segments of the RNA. Virions also synthesize an 8.4 kbp double-stranded circular DNA that lacks one copy of the terminal repetition, as well as viral DNA longer than 9 kbp. The enzymatic machinery in the virions of retroviruses therefore appears to be responsible for all the steps involved in making fully double-stranded linear and one form of circular DNA.


Transformed mammalian cells secrete specific proteins and phosphoproteins. We have examined the proteins secreted into the growth medium by normal and transformed cells. Transformed cell lines from several mammalian species all secrete proteins in the 58,000 dalton molecular weight range. These proteins are all immunologically related and are secreted at low levels or not at all by the parental normal cell lines. Secretion of the 58K proteins occurs with either DNA or RNA virus transformation and with spontaneous transformation. The transformed cells also secrete phosphoproteins in the same size range, but these are immunologically distinct from the 58K proteins mentioned above. The sizes of the phosphoproteins are species-specific and unrelated to the transforming virus. Incubation of conditioned media from transformed cell cultures with gamma-32P-ATP labels phosphoproteins of the same sizes, indicating the presence in the media of both protein kinase and substrate. All three properties (58K protein, phosphoprotein, in vitro phosphorylation) are closely correlated with transformation in cells transformed by temperature-sensitive viruses. The biological implications of these results remain unknown, but the results may be relevant to recent data on the (phospho)proteins and protein kinase encoded by RNA tumor viruses and the molecular basis of the transformed phenotype.


Evidence for a gonad-specific receptor for H-Y antigen: binding of exogenous H-Y antigen to gonadal cells is independent of beta 2-microglobulin. This report addresses the question whether two different types of binding exist for the reaction of H-Y antigen with the cell surface. Anti-H-Y antiserum in the presence of complement was cytotoxic only for gonadal cells expressing their own H-Y antigen, but not to ovarian cells loaded with H-Y antigen. H-Y antigen was co-redistributed with beta 2--microglobulin on newborn testicular cells, but some residual H-Y activity was found on similarly treated testis cells from 15 day old rats. After beta 2--microglobulin redistribution, testis cells maintained their binding capacity for exogenous H-Y antigen prepared from epididymal fluid or Daudi cell culture supernatants. This result suggests that exogenous H-Y antigen is bound via a gonad-specific receptor which is independent of beta 2--microglobulin and that this type of binding for H-Y antigen is different from the beta 2--m-associated expression of H-Y antigen on the cell surface.


Multiple genes coding for the androgen-regulated major urinary proteins of the mouse. We have purified a cDNA fragment complementary to the mRNA coding for one of the major urinary proteins (MUPs) synthesized in the mouse liver. Using this cDNA as a hybridization probe, we have shown that the level of MUP mRNA is lower in the livers of females and castrated males than in those of males. The addition of testosterone to females and castrated males results in an increase in the concentration of the mRNA to levels found in males. There are approximately 15 gene per haploid genome coding for the MUPs; this allows a possible new interpretation of some of the genetic data concerning the regulation of levels of the different MUPs in the urine (Szoka and Paigen, 1978). Finally, we have shown that mouse MUP and rat alpha 2u-globulin mRNA share common sequences, but that there are surprising differences in gene number and regulation of the genes in these two closely related animals.


Transitory increase in chromosomal DNA (Fleulgen) during floral differentiation in Rhoeo discolor. Scanning cytophotometric measurements on 3200 telophase and 1700 interphase nuclei (Feulgen-stained) in vegetative and reproductive buds of Rhoeo discolor revealed a transitory increase in staining intensity in more than half of the cells in early differentiating floral buds. The differences between the vegetative and floral nuclei are significant at the 0.001 level of probability and highly reproducible, independent of the type of hydrolysis used. We suggest that the different Feulgen extinction values reflect different nuclear DNA amounts, because methodical errors can fairly be excluded. The occurrence of an extra DNA (control DNA) of the kind of the floral DNA' detected by Wardell and Skoog (1973) and Wardell (1976) in tobacco is discussed.


[Possibilities for improvement in the histocytological comparison of tumor elements]. Pappenheim's staining is indispensable for comparisons between cytological and histological pictures in oncology. A well-stained tumour tissue section then offers advantages similar to that of smear cytological pictures without loss of syntopic relationships. For general pictures, however, haematoxylin-eosin taining offers most advantage.


[Changes of various proteins in older blood stains]. 26 unequally old groups of blood stains up to 180 days old were examined for the presence of albumin, Ig A, Ig G immunoglobulins, beta 1 C globulin and transferrin. To ensure different external conditions, each group was composed so as to contain blood stains of the same age but preserved under different conditions and on different types of underlying material. Albumin and Ig G immunoglobulin proved to be among the most stable ones. However, due to variations in the results the practical uses of this type of blood stain age estimation appear to be problematic.


Induced synthesis of chromochelatin, the low molecular weight bismuth-binding protein in rat kidneys. Bismuth administered subcutaneously to rats as BiCl3 is deposited in the kidneys, where it is bound to two classes of proteins: one of high molecular weight and a fraction of molecular weight approx. 7500 (chromochelatin). The latter fraction prevails on repeated exposure to bismuth. The bismuth-binding protein is heterogenous and using polyacrylamide gel may be divided into three fractions of which all contain bismuth and copper. In parallel with increasing concentration of chromochelatin due to bismuth administration, the incorporation of L-[35S]cysteine is elevated in all three fractions. The incorporation is augmented especially if repeated administration of bismuth is applied. Cycloheximide (CH) completely abolishes the inducing effect of bismuth on the incorporation of L-[35S]cysteine into chromochelatin both following single and repeated administration of bismuth. Actinomycin D (AcD) eliminates the incorporation only in the case of single dose of bismuth. The obtained results suggest that the elevation of chromochelatin levels in the kidney following administration of bismuth is due to the induction of the de novo protein synthesis.


[Effect of human interferon on viral production in a cell line chronically infected by a type D retrovirus (Mason-Pfizer virus)]. Human interferon specifically inhibits the viral multiplication in a human cell line infected by a type D retrovirus, the Mason-Pfizer virus (MPV). This inhibition is less important than for type C viruses.


[Impairment of rapid axonal transport and concomitant anomaly of smooth endoplasmic reticulum in acrylamide induced neuropathy]. The axonal transport of proteins was studied by radioautography in preganglionic axons of ciliary ganglia in Leghorn chickens treated by acrylamide. The slow axonal transport of proteins was hardly affected. In contrast, the fast axonal transport was severely impaired. Indeed, radioactive proteins accumulated focally at the periphery of several preterminal axons in regions showing a local disorganization of the smooth endoplasmic reticulum which seemed to be one of the earliest changes induced by acrylamide.


Adriamycin, bleomycin, vinblastine and imidazole carboxamide (ABVD) therapy for advanced Hodgkin's disease resistant to mustine, vinblastine, procarbazine and prednisolone (MVPP). Forty-one previously treated patients with advanced Hodgkin's disease were treated with a combination chemotherapy regimen -- ABVD (adriamycin, bleomycin, velbe/vincristine, imidazole carboxamide). Complete remission was achieved in three patients (7%), partial remission in 23 (56%), and no response in 15 patients (37%). The median survival of the group was 12 months from the start of therapy. Survival correlated with response to treatment. No apparent benefit resulted from giving more than six courses of therapy (3 months' treatment time). There was no serious haematological toxicity in patients without bone marrow disease, and bleomycin and adriamycin toxicity was not apparent clinically or at autopsy in the dosages employed in the regime. Alopoecia was very frequent. The role for ABVD, other than as a primary induction regimen, appears to be in conjunction with other regimens in the induction of patients with adverse features at presentation or during induction; or in the salvage and palliation of patients who demonstrate a response but fail to achieve remission, either initially or at relapse, with MOPP (mustine, vincristine rpocarbazine, and prednisolone) or MVPP (mustine, vinblastine, procarbazine and prednisolone.


New micro-turbidimetric method for determination of protein in cerebrospinal fluid and urine. We report a new micro-scale (0.1-mL sample) turbidimetric method for determination of protein by use of benzethonium chloride in alkali. The method is highly specific for protein, has a higher sensitivity than the classic method of Lowry et al., and shows satisfactory reproducibility and recovery. The turbidity produced in our method is the same for albumin and gamma-globulin and is more stable than in Meulemans' method (in which sulfosalicylic acid is used) or in the method of Bossak et al. (in which trichloracetic acid is used). In contrast to Pesce and Strande's method, there is no manipulative loss of protein.


Hepatic function assessed (in rats) during chemotherapy with some anti-cancer drugs. Using rats, we studied how best to assess hepatic damage after administering therapeutic doses of each of five anti-cancer drugs or of the hepatotoxin, carbon tetrachloride. As indexes, we compared measurement of the concentration of administered antipyrine in plasma with measurement in serum of alpha-fetoprotein or of the activities of five enzymes that reportedly best reflect hepatic damage. The biological half-life of antipyrine in the plasma was increased more than threefold on pretreating the rats with any of the five cytotoxic drugs or with carbon tetrachloride. In contrast, the concentrations of alpha-fetoprotein, alkaline phosphatase, gamma-glutamyltransferase, or glutamate dehydrogenase were not consistently increased. Of the enzymes tested in serum, aspartate aminotransferase and ornithine carbamoyltransferase best indicated hepatic impairment resulting from the treatment with anti-cancer drugs. Our results imply that determination of the pharmacokinetics of marker drugs such as antipyrine better indicates hepatic dysfunction induced by cytotoxic agents than does measurement of the enzymes liberated into serum as a result of damage to liver mitochondria.


IgD myeloma protein with "unreactive" light chain determinants. Serum from a patient with multiple myeloma showed a monoclonal protein, classified by immunoelectrophoresis as IgD. Immunofixation electrophoresis and immunoelectrophoresis failed to demonstrate a precipitation reaction between the paraprotein and antisera to immunoglobulin light chains. The light chains of the monoclonal protein, immunologically inaccessible in the intact molecule, reacted with anti-lambda chain antisera only after reduction and alkylation of the paraprotein. Moreover, interpretation of the immunoelectrophoretic patterns was hampered by the presence in patient's serum of free lambda chains having about the same mobility as that of the paraprotein.


The quantitation of pregnancy specific beta 1-glycoprotein by enzyme linked immunoassay. A rapid enzyme linked immunoassay for pregnancy specific beta 1-glycoprotein is described. The method is sensitive and precise (within batch C.V. = 6.5-7.4%) and should be suitable for the biochemical monitoring of pregnancy and the investigation of patients suffering from various malignancies.


[Determination of proteins in cerebrospinal fluid of adults using two immunochemical methods (author's transl)]. A study of CSF proteins by electrophoretical and immunological techniques suggests the Laser immunonephelemetrical method is suitable as a "Standard method". The average levels of albumin, IgG, IgM, IgA and alpha-2-macroglobulin have been determined and the correlations between these levels have been calculated. The values of albumin and IgG allow a classification of neurologic diseases according to a diagram. The variations of IgM, IgA and alpha-2-macroglobulin levels are not yet explained.


Progressive rubella panencephalitis: immunovirological studies and results of isoprinosine therapy. Two patients with progressive rubella panencephalitis, one with and one without stigmata of congenital rubella, were treated for 9 months with isoprinosine and showed continued clinical deterioration. Immunoviorological studies performed before, during and after treatment were unaffected by drug therapy. The virus was recovered on one occasion from the lymphocytes of one of these cases. Neither patient showed any major defects in cellular or humoral immunity. However, the lymphocytes of the patient with stigmata of congenital rubella failed to respond to rubella virus in vitro and had a heat stable, non-dialysable serum inhibitor of in vitro protein A stimulated proliferative responses. Both patients' serum interfered with the production of interferon by normal donor lymphocytes following stimulation with rubella and varicella virus antigen. Increasing serum titres of interferon which did not appear to be lymphoid or immune-specific in origin were found in these two cases.


A case of trisomy 22 in Pongo pygmaeus.

A case of trisomy 22 in Pongo pygmaeus. A behaviorally and clinically abnormal female orangutan was analyzed cytologically using general banding techniques and by an alkaline silver method for staining nucleolus organizer regions. The karyotype had 49 chromosomes, including an extra chromosome 22 (49,XX + 22). No variant chromosome types or heterozygous structural rearrangements were found. Nine of the 14 large acrocentric chromosomes, Nos. 11--17, and three of the five presumptive human G-group equivalents, i.e., two of three chromosomes 22, and one chromosome from pair 23, exhibited positive silver staining of the nucleolus organizer region (NOR).


T antigen banding on chromosomes of simian virus 40 infected muntjac cells. Chromosomes were prepared from mitotic munjac cells 48 to 72 h after infection with SV40 virus. When stained for SV40 T antigen by indirect immunofluorescence, all chromosomes within an infected cell were fluorescent, indicating the presence of T antigen. Furthermore, the chromosomes were not uniformly stained but appeared to have regions of high and low fluorescence intensity. A variety of controls showed that the banding patterns are specific and highly reproducible and may indeed reflect the binding sites of T antigen. The bright, fluorescent bands T antigen were found to correspond to bands visualized by trypsin-Giesma staining (G-bands) and also by quinacrine staining (Q-bands). Current knowledge of chromosome banding indicates that Q-bands reflect the distribution of AT-rich regions along the chromosome. From the DNA sequence of SV40, it is known that one of the T antigen binding sites contains AT-rich sequences; thus, T antigen banding might be due to the base-specific binding of T antigen to chromatin. In addition, these bands have been implicated as centers for chromosome condensation and units in control of DNA replication. While the functional significance of T antigen binding has yet to be determined, the SV40-muntjac system provides an unusual opportunity to study the interaction of a known regulatory protein with mammalian chromosomes.


Sterility in hybrid cattle. I. Distribution of constitutive heterochromatin and nucleolus organizer regions in somatic and meiotic chromosomes. The distribution of constitutive heterochromatin and nucleolus organizer regions (NOR's) in somatic as well as in meiotic chromosomes of Bos taurus, Bos banteng, Bison bison, and their hybrids are analyzed. C-bands are present in the centromeric regions of every autosome. The X chromosome does not show a distinct C-band in the centromeric region, whereas the Y chromosome contains an appreciable amount of C-band material. In somatic metaphases, NOR's are present on the telomeric ends of five pairs of autosomes. During pachytene, five autosomal bivalents contain NOR's on their terminal ends. Meiotic preparations made from sterile bulls did not contain stages beyond the degenerating pachytene, which are C-banding, more frequently showed clustering of heterochromatin than did the pachytene stage in normal bulls.


Heterogeneity of constitutive heterochromatin in somatic Syrian hamster chromosomes. Syrian hamster constitutive heterochromatin was analyzed for C-band distribution and for BrU late-replication pattern. Characteristic for this species is relatively large amounts of sex-chromosome and autosomal heterochromatin. The distribution of constitutive heterochromatin was determined. The long term of the X chromosome, the whole Y, the short arms of 8 autosomal pairs, the long arm of the smallest metacentric pair, and the centromeric regions of 12 pairs stained intensely dark on C-band preparations. In contrast to the heterochromatin in the centromeric regions, the autosomal short-arm heterochromatin has an increased susceptibility to the denaturation process, as indicated by prolonged exposure to NaOH or Ba(OH)2. Such further exposure to denaturing agents results in an intense dark stain only on the sex-chromosome heterochromatin and centromeric regions of the autosomes. The BrdU late-replication pattern demonstrated that the late-replicating regions correspond to C-bands. Centromeric regions replicate late in the S phase; however, no centromeric region is among the latest replicating segments of the complement. Centromeric and noncentromeric heterochromatin are two distinct categories of constitutive heterochromatin.


Demonstration of specific heterochromatic segments in the orangutan (Pongo pygmaeus) by a distamycin/DAPI double staining technique. Orangutan metaphase chromosomes, obtained from a female animal with trisomy 22, were stained by a recently developed distamycin/DAPI fluorescent technique which had been shown to differentiate specific C-bands on human chromosomes, as well as by other banding techniques. Distamycin/DAPI-brilliant fluorescence was observed in the short arm regions of acrocentric chromosomes 11--17, 22 and 23, and a brightly fluorescent paracentromeric band was seen on chromosome 8. A smaller amount of fluorescence was found adjacent to the centromere of most of the other chromosomes. Sequential distamycin/DAPI and Giemsa C-staining of the metaphases revealed that the "hot-spots" on acrocentrics correspond to C-band material in their short arm. The less intensely fluorescent centric bands on other chromosomes coincide with centromeric C-bands. Reverse fluorescent staining of organutan chromosomes with chromomycin A3 revealed brightly fluorescent regions at short arms of some acrocentrics probably  confined to the satellite, either in a heteromorphic form (Nos. 11, 14, 17) or of similar size (No. 22).


Palliation of massive hemoptysis from unresectable carcinoma of the lung. Unresectable carcinoma of the lung has traditionally been recognized as a contraindication to surgery in massive hemoptysis. A 60-year-old man had massive hemoptysis. At surgery an unresectable neoplastic mass invading the mediastinum and great vessels was encountered. Subtotal resection was accomplished using a stapler (Autostapler). The margins of the bronchial and vascular staples were of necessity placed directly through the tumor. The patient had an uneventful recovery and has survived six months without further hemoptysis. This method is presented as an effective strategic retreat under circumstances not permitting definitive therapy.


[Acid reduction and ulcer healing through vagotomy: is an inhibition of histamine release an essential reason for this?]. In a prospective, consecutive study the histamine content of corpus mucosa and the basal and maximally stimulated acid output were measured in male patients who had selective vagotomy to correct a chronic duodenal ulcer. The increase in histamine content after vagotomy was directly proportional to a decrease in maximum acid output. The relationships between histamine content, recurrent ulcer, and reduction in acid output point to a causal relationship between inhibition of histamine release and successful vagotomy.


[Plasma histamine level during and following kidney allotransplantation in man]. In human kidney allotransplantation, elevated plasma histamine levels were measured before surgery, following revascularization, and in single cases also several days after surgery. The maximum extent of this histamine release must be tested with respect to time and to localization. Its significance must be established. The intermittently increasing plasma histamine levels (greater than 1 ng/ml) must be considered as a possible risk regarding stress ulcer pathogenesis.


The mechanism of C-binding: depurination and beta-elimination. C-banding of chromosomes involves the differential solubilization of fragmented DNA from euchromatin by three sequential treatments: 1. Acid, 2. Mild base, 3. Hot salt. The data indicate solubilization is effected by 1) depurination, 2) DNA denaturation, 3) chain breakage of the depurinated sites respectively in the three treatments. Conditions were found wherein each treatment in proper sequence was necessary for C-banding and the appropriate chemical reactions were measured in these treatment conditions. The acid treatment (0.2 N HCl) depurinates chromosomal DNA at the rate of 0.26 x 10(-6) purines/dalton min to an alkaline molecular weight of 10(5) daltons but does not break the depurinated sites. Bleomycin can substitute for acid as a base removing agent. Sodium borohydride, by reducing the depurinated sugar's aldehyde thereby preventing chain breakage by the beta-elimination reaction, reversibly inhibits DNA-extraction. Chain breakage at the DNA's apurinic sites occurs not in the 2 min mild alkali treatment where the half-life for breakage is 26 min but in the 18 h hot salt treatment where the half-life for chain breakage is 1-2 h. Most of the DNA extraction occurs in the hot salt as 10(5) dalton fragments as measured in formamide gradients. Bleomycin is introduced as a substitute for HCl; it removes nitrogenous bases from DNA in situ while better preserving the morphology of the final C-banded chromosomes.


Light microscope analysis of meiotic prophase chromosomes by silver staining. A method is described for the silver staining of the synaptonemal complex in surface-spread mammalian spermatocytes for light microscope examination. The method is quick, reliable, of broad applicability, and provides a means of making karyotype analysis at meiotic prophase. Many hundreds of suitable cells can be examined in an average preparation in a relatively short space of time. It has so far been applied only to mammalian spermatocytes, but could be used for karyotype analysis in oocytes of mammals and also applied to gonocytes of non-mammalian species.


Forums in gastrointestinal roentgenology: transhepatic portal venography and selective obliteration of gastroesophageal varices using isobutyl 2-cyanoacrylate (bucrylate). Five patients with Child's class C alcoholic cirrhosis and actively bleeding gastroesophageal varices underwent transhepatic portal venography and selective obliteration of varices with isobutyl 2-cyanoacrylate (Bucrylate). Temporary control of bleeding was obtained in four patients and complete control in one. This new technique is best utilized to stop active variceal hemorrhage in patients who are not candidates for portasystemic shunt surgery or to control bleeding while the patient's general medical condition is improved to decrease the risk of subsequent shunt surgery.


Rod-shaped organism in the liver of a patient with Whipple's disease. Histological review of a liver biopsy from a patient with known Whipple's disease revealed a prominence of Kupffer cells containing PAS-positive granules. Electron microscopy revealed rod-shaped organisms in the Kupffer cells but the presence of these structures were not associated with overt liver injury. This is thought to be the first reported demonstration of these bacillary bodies in this location.


[Liver function studies under the influence of hormonal contraceptives (sequential preparations)]. 20 fertile women who were treated with mestranol as oestrogen and both gestagenes chlormadinonacetate and norethisteronacetate were investigated. Alkaline phosphatase, ASAT, ALAT, alpha-amylase, cholesterol, bilirubin, serumproteins, indocyanine green half time, paper electrophoresis of serumproteins, thymol and zinc sulfate turbidity tests were examined during the first therapy cycle. Elevation of ALAT activity (6,3 I U/l to 12,14 u/l) was found during treatment with mestranol/chlormadinonacetate. A depression of ALAT (up to 5,34 u/l) was observed under additional therapy with gestagene chlormadinonacetate. Statistical significance was noted only for ALAT and alpha 1 globuline under sequential therapy with mestranol/norethisteronacetate.


Changes in seizure susceptibility, sleep time and sleep spindles following thalamic and cerebellar lesions. The present experiment attempted to clarify conflicting evidence on the relationship of sleep spindles to seizure activation. Seizure thresholds were calculated in minutes post-injection following IP administration of the convulsant drug monomethylhydrazine (MMH) to cats with lesions intended to alter the occurrence of spontaneous 12-15 c/sec sleep spindles recorded from sensorimotor cortex. Twelve cats with bilateral cortical and subcortical recording electrodes were divided into 3 groups receiving electrolytic lesions in the dentate nucleus (group I), the ventrobasal (VB) thalamus (group II), or in one of various 'control' regions (group III). Lesion sites in group III animals avoided primary afferent pathways to VB thalamus, destruction of which has been found to enhance sleep spindle activity, and included cerebellar white matter and ventral pontine tegmentum. Prior to the MMH trials, baseline EEGs were obtained during pre- and post-lesion conditions. Following the MMH trial, lesions were verified histologically. Results of the MMH trial revealed that animals with dentate and ventrobasal thalamic lesions showed elevated seizure thresholds and slow wave sleep times relative to their own pre-lesion EEG baselines and to the pre- and post-lesion baselines of control animals. Furthermore, an increased incidence of sleep spindles was associated with dentate lesions while animals with ventrobasal thalamic lesions showed a shift in frequency from 8-11 c/sec to 12-15 c/sec activity during that state. These findings are compatible with the view that sleep spindles do not facilitate seizure activation and may, in fact, exert a protective influence.


Prostaglandin E1-induced latent epileptogenic foci. Suprafusion of 125 microliter 6% KCl solution over the visual cortex of rabbits 2-24 h after they suffered a prostaglandin (PG) E1-induced epileptic seizure was found to cause a recurrence of seizure activity. The initial seizure was induced by the cortical suprafusion of PGE1 over the left visual cortex of PG transport inhibitor-pretreated rabbits. Control animals that were not pretreated with PG transport inhibitors (bromcresol green or probenecid), or received suprafusion of saline or PGF2 alpha rather than PGE1, did  not show initial seizure activity. In these animals, and in animals that had PG-induced seizures 72 h before KCl administration, the KCl solution caused only inhibition of the visually evoked response but no seizure activity. The results are interpreted to indicate that under appropriate conditions PGE1 can create a latent epileptogenic focus which can be reactivated by KCl. It is suggested that since PGE1 is produced by the brain normally, and in increased amounts as the result of overstimulation, irritation or trauma, this potent autacoid may play a role in the spontaneous development of latent epileptogenic foci or the recurrence of epileptic seizures.


Analogue analyser for on-line eye movement detection. A system of single movement detection is obtained by discriminating the velocities and orientations of eye ball displacements. The orthogonal components of eye velocity (Vx and Vy) are generated from the horizontal (X) and the vertical (Y) components of the movements by means of two derivative circuits and the velocity modulus (V) is generated through a vector operator from Vx and Vy. The onset and end of individual movements are detected on the basis of a preselected V, Vx or Vy threshold and, for every movement thus identified, the integral function of V(t), Vx(t) or Vy(t), characteristic of the type of movement, is generated in such a way that its final value represents ball displacement.


Assessment of the H-reflex excitability curve using a cubic spline function. A procedure for modeling H-reflex recovery curve data is described. The procedure involves fitting a cubic spline function to the recorded data points in such a way that the goodness of fit is determined by the standard error of the mean of each point. The cubic spline function possesses numerous advantages over other subjective and objective procedures for extracting information from the excitability curve.


Nocturnal and diurnal sleep in Macaca sylvana. In Macaca sylvana restrained in chairs, continuous 24 h recordings were obtained of scalp EEG, neck EMG, bilateral EOG, motility of the head and lever manipulation. A total of 32 days were studied in 8 monkeys. Recordings were divided into epochs of 30 sec and analyzed in a PDP-12 computer. Four stages of sleep and 5 stages of wakefulness were identified by combination of the above data. Results were as follows: (1) During the night, there was 21% wakefulness and during the day 20% sleep, including a considerable amount of REM. (2) Recordings of spontaneous motility of head and hands proved an excellent indicator of sleep-wakefulness cycles. (3) Spectral analysis revealed the cyclic characteristics of non-REM sleep, with peaks at 360, 149, 72, and 55 min. (4) Stages of wakefulness had ultradian cycles, and stage W-2 was the most important in number and duration of occurrences. (5) Night wakefulness had characteristics different from day wakefulness. (6) Study of sequences showed that stage II was the least differentiated being transitional among the other stages, while stage III-IV was never preceded by wakefulness or REM, and almost always it followed stage II (99.0% of the time). (7) The high statistical significance of results obtained under restraint in different monkeys suggests that this situation has great potential value in the investigation of physiological mechanisms of ultradian rhythms.


Cold-induced diminution of paradoxical sleep in man. Prolonged exposure to cold produced a chronic diminution in PS (PS-hyposomnia) primarily in the tonic component of PS. No significant change occurred in the REM (phasic or obligatory) component of PS. An inverse correlation was found in the activity of the pituitary-adrenal cortical system and the level of PS. The classical rebound phenomenon that occurs after PS deprivation was not observed in this study and it is suggested that the rebound effect characteristic of PS deprivation is related not to total PS but to its phasic (obligatory) component.


Visual and computer-based analysis of 24 h sleep-waking patterns in the dog. Sleep and waking EEG patterns recorded over 24 h periods in 7 adult beagle dogs were studied both visually and by computer. Online analysis was carried out using a mini-computer. The following quantitative data were computed and listed (and/or stored on disc) at 30 sec intervals: power spectrum analysis of one cortical derivation by means of Fast Fourier Transformation, the spectrum being divided in 4 bands (0.5-3.5, 3.5-7.5, 7.5-13.5, 13.5-25 c/sec); the power contained in the 3.5-7.5 c/sec band of the hippocampal derivation; a spindle detection algorithm empirically defined and based on the power contained in the 10.5-14.5 c/sec band of subepochs of 0.8 sec and the background power; average EMG and EOG amplitudes. Plots were made of the quantitative data (on the y axis) showing evolution with time (on the x axis). Comparisons with the y ordinates enabled a visual estimate of stage to be made. Automatic classification was done by means of minimal distance, using visually selected epochs and calculated parameters as references. Visual and computer-based analyses allowed the following patterns to be defined: wakefulness, transitional stage, light slow wave sleep, deep slow wave sleep and REM sleep. Sleep-waking cycles of 20-30 min alternated during the 24 h period with rapid transitions from one stage to another.


Coloured pattern displacement and VEP amplitude. The results of this experiment confirm that evoked potential amplitude is linear with checkerboard pattern displacement. We have also found that this linear relationship holds for red, green and blue patterns. The hypothesis that there would be no significant differences between the amplitude of the evoked potential to colour/'black' stimulation and a white/'black' stimulus of equivalent luminance has been substituted. Differences were found between colours. The mean level for the blue pattern was lower than that for the red and the green patterns. We have further confirmed the relationship between luminance and the latency of the evoked potential. Differences in latency were found between all conditions in this study, suggesting that more accurate methods of measuring luminance are required in studies using colour pattern displacement if latency measurements are the main focus of the study.


Spinal evoked potential in man: a maturational study. Summated evoked potentials to peroneal nerve stimulation which arise in the cauda equina and spinal cord afferent pathways were recorded from surface electrodes placed over the spine of 95 infants, children and adults. The conduction velocity of these potentials from lumbar to cervical recording sites was calculated. Additionally, segmental conduction velocities over peroneal nerve, caudal and rostral spinal cord were determined. In all age groups the speed of conduction up the spine was non-linear. It was slower over caudal spinal cord segments than over peripheral nerve or rostral cord. All these velocities were about half adult values in the newborn and progressively increased with age. The conduction velocity over peripheral nerve was within the adult range by 3 years of age. The speed of conduction over the spinal cord did not reach adult values until the 5th year. This suggests that spinal cord afferent pathways mature at a slower rate than peripheral nerve fibers.


Effects of H-reflex conditioning upon the contralateral alpha motoneuron pool. H-reflex recovery curves have been elicited by subliminal conditioning stimuli applied to the ipsilateral and contralateral posterior tibial nerves in 10 healthy female subjects. In both types of recovery curve there was clear evidence of a period of facilitation in the ipsilateral soleus motoneuron pool 75-250 msec after the conditioning stimulus. These results indicate the bilateral nature of the facilitation and show it to be most probably produced by stimulus-evoked inputs as opposed to twitch-evoked inputs. If the facilitation is produced by descending long-loop reflex influences, then complementary evidence is provided for previous electromyographic data showing the bilaterality of long-loop reflexes evoked by percutaneous electrical stimulation. It is impossible, however, at the present time, to rule out the possible involvement of cutaneous afferent discharges or other stimulus evoked inputs in the late facilitation.


Derivation of reliable electromyograms and their relation to tension in mammalian skeletal muscles during synchronous stimulation. There exists a good correlation between the measured electrical activities and isometric twitch tension in the cat soleus muscle during synchronous stimulation. For an unbiased sampling of electrical activities by averaging a number of electromyograms over the muscle concerned, a relation of the form E = 0.98T + 5.35 has been established. It is hoped that this relation will prove valuable in clinical application where EMGs are used. Electrode types for EMG pick-up differ in terms of the signal recorded due to the difference in the spatial and temporal addition of individual motor unit firing and the constructional difference of the electrodes. Fine wire pairs are the best for linearity and ease of application. Whe surface electrodes are used because of their non-invasive nature, care must be exercised to established the exact relation between EMG and tension. EMG recordings from different sites within a muscle show considerable variation. A more reliable measure can be obtained by external averaging of multiple pairs of electrodes.


Event-related potential changes in healthy aged females. Neurophysiological changes in the central nervous system were demonstrated with EEG even-related potentials in healthy, aged women. Compared to young women, the aged women showed decreased amplitude of the late sustained potential (SP), increased P2 latency, disruption of the normal stimulus intensity-response amplitude function of P2 and increased amplitude of the P1 component. These age-related changes are interpreted as neurophysiological reflections of CNS deterioration found in non-senile elderly persons.


Combined modulating effects of the general arousal and the specific hunger arousal on the olfactory bulb responses in the rat. The combined modulating effects of the general level of arousal and specific hunger arousal on the olfactory bulb responses were investigated in the rat. Vigilance state parameters and multi-unit mitral cell activity were recorded in freely moving animals stimulated by control odours and by their usual food odour, either in the hungry or the satiated state. The nutritionally modulated bulb responses towards food odour were observed only for high arousal level (wakefulness). In rapid eye movement sleep (REMS), no olfactory response occurred. In slow wave sleep (SWS), one observed either a high bulb responsiveness to stimuli with neocortical arousal, or a general inexcitability. Each odorous stimulus in SWS elicited a higher neocortical arousal rate in the hungry than in the satiated state, as did food odour compared with control odours in both nutritional states. In SWS, a progressive alteration of the nutritionally modulated responses occurred at first at the bulb level and later for inner structures. Rats fed 2 h a day displayed a reversed circadian sleep-waking cycle and a lower SWS proportion compared with rats fed ad libitum. The hunger arousal could quantitatively and qualitatively modulate the activity of structures regulating the sleep-waking pattern.


Alpha and beta coma in drug intoxication uncomplicated by cerebral hypoxia. Four patients who were rendered comatose or stuporous by drug intoxication, but who were not hypoxic, are described. Three patients received high doses of chlormethiazole for alcohol withdrawal symptoms, and one took a suicidal overdose of nitrazepam. The patient with nitrazepam overdose and two of those with chlormethiazole intoxication conformed to the criteria of 'alpha coma', showing non-reactive generalized or frontally predominant alpha activity in the EEG. The fourth patient who was unconscious after chlormethiazole administration exhibite generalized non-reactive activity in the slow beta range. All four recovered completely without neurological sequelae following the withdrawal of the offending agents. The similarities between the effects of structural lesions and pharmacological depression of the brain stem reticular formation are discussed. It is suggested that in both situations disturbed reticulo-thalamic interactions are important in the pathogenesis of alpha coma. It is concluded that when this electroencephalographic and behavioural picture is seen in drug intoxication, in the absence of significant hypoxaemia, a favourable outcome may be anticipated.


The EEG at different stages of acute secondary traumatic midbrain and bulbar brain syndromes. One hundred and thirty EEGs were analysed from 113 patients with acute secondary traumatic midbrain and bulbar brain syndromes. The EEG pattern was related to the stage of the midbrain syndrome caused by supratentorial brain shift. A decrease in the number of different EEG patterns was associated with increasing intracranial pressure. Unfavourable prognosis was indicated by the disappearance of sleep or sleep-like activities alternating pattern and loss of reactivity. Lateralization by the EEG proved to be superior to clinical findings in full stages of the midbrain syndrome. EEG abnormalities due to the herniation itself interfered with EEG changes due to secondary circulatory, respiratory and metabolic encephalopathies. In such cases, the above mentioned regularities were blurred.


Inhibition in penicillin-induced epileptic foci. A previous study indicated that the early surface negative component (associated with recurrent inhibition) of the evoked potential recorded from cat pericruciate cortex, subsequent to pyramidal tract stimulation, was altered after application of penicillin to the cortical surface (Van Duijn et al. 1973). This suggested that decreased effectiveness of recurrent inhibition might be the basis for epileptogenicity of penicillin. To verify that recurrent inhibition is functionally decreased in the penicillin epileptic focus and to assess alternative sites for penicillin action, this phenomenon was investigated at the cellular level. Neurons were recorded extracellularly and response to stimuli monitored throughout the transition from normal cortex to epileptogenic cortex. Stimuli employed were peduncular stimulation (to test recurrent inhibitory pathways), epicortical stimulation (to test inhibitory pathways, bypassing the recurrent collateral system), and forepaw footpad shock (to test the responsiveness ofneurons to afferent input). In normal cortex, PT cells were inhibited by peduncular or epicortical stimulation and excited by forepaw stimulation, with the excitation followed by a period of inhibition. In the penicillin focus, inhibition was not observed in response to any of the 3 stimuli, and the excitatory response to forepaw stimulation was maintained. The bursting non-PT cells, most likely candidates for interneurons, exhibited excitation in response to peduncular and epicortical stimulation, consistent with involvement in inhibitory pathways. Nonetheless, in the penicillin focus, excitatory response to peduncular and epicortical stimulation was maintained. Excitatory response to forepaw stimulation was also maintained in the penicillin focus. The results demonstrate a loss of effectiveness of recurrent inhibition measured at the PT cell body in the penicillin focus. Further, the reduction in inhibitory feedback occurs in conjunction with maintained or enhanced excitability of the neurons which are most likely candidates for inhibitory interneurons. Thus, penicillin is most likely exerting its effect at the inhibitory synapses onto PT cells in the cortex, thereby allowing excitatory input to have greater influence on neuronal firing.


Automatic recognition of inter-ictal epileptic activity in prolonged EEG recordings. A method of automatic recognition and quantification of inter-ictal epileptic activity in the human EEG had previously been developed and tested using short recordings from awake subjects. This paper describes the adaptation of the method for use during overnight recordings in free-moving unattended patients, in combination with the already existing seizure monitoring system. EEG s were recorded from scalp and sphenoidal electrodes, using cable telemetry and a PDP-12 computer. The spike and sharp wave recognition method allowed the on-line analysis of 16 channels. A section of the 16-channel EEG including 1 sec before and 1 sec after each detected spike was saved on digital magnetic tape. Upon completion of the monitoring session, the tape was played back on the EEG machine, giving a discontinuous tracing of spike sections; this constituted a highly concentrated view of the inter-ictal epileptic activity, in traditional paper form. The spike sections were further analyzed by computer to determine and display on the computer terminal the spatial and temporal distributions of the epileptic activity, providing a complete synopsis of the recording. Several examples of the type of information available from this anslysis are discussed in detail. False detection rates are given for 34 six hour recordings, indicating a high vari ability in the performance, mainly because of artefacts. It is concluded that the final computer displays could only be trusted after visual inspection of the EEG sections provided on paper. The variety of morphologies of artefacts appeared to preclude a total automatic elimination.


Vestibulo-ocular responses during the states of sleep in the cat. The vestibulo-ocular response (VOR) was recorded during natural sleep in cats with chronically implanted electrodes. By using a small amplitude sinusoidal head rotation (11 degrees) peak-to-peak at 0.4 Hz) which elicited only slow compensatory eye movements, the VOR amplitude was found to decrease steeply (down to 40% or less) during slow-wave sleep. The phase of the VOR with respect to head position remained approximately constant. With a larger amplitude of sinusoidal rotation (320 degrees peak-to-peak at 0.05 Hz) the VOR response included nystagmus. During slow-wave sleep, nystagmus disappeared and the overall amplitude of the response decreased. Simultaneously, the phase of the eye response with respect to head position shifted by up to 90 degrees in advance. During paradoxical sleep, VOR disappeared in all cases and was replaced by randomly occurring bursts of rapid eye movements. These results are discussed in terms of a parametric control model of VOR.


Sleep onset and first cycle of sleep in human subjects: change with time of day. The first cycle of sleep was studied in different situations: normal night sleep, naps, diurnal sleep after night shifts (3 x 8 shift workers). Results show two types of first cycle: some started with SWS (normal cycles), others with REM (sleep onset REM periods: SOREMPs). (1) Normal cycles: the length of SWS in the first cycle was positively correlated with prior wakefulness; conversely, the latency of SWS decreased as prior wakefulness increased; the decrease was due to the decrease in the length of the previous stage II or of the sleep onset latency (SOL). Length of sleep onset (SO) showed only few variations. The structure of the first cycle of shift workers' sleep probably reflects an important sleep loss. (2) SOREMPs occcurred during diurnal sleep. Some hypotheses about these cycles are discussed including REM 'pressures' (circadian, sleep loss) and inter-individual variations.


Relationships between the late component of the contingent negative variation and the bereitschaftspotential. The purpose of this study was to determine whether the late component of the contingent negative variation (CNV) in a S1-S2-respond paradigm shares critical features with the Bereitschaftspotential (BP) prior to self-paced voluntary movements. In a group of 8 subjects, the late CNV and the BP exhibited: (a) similar effects of response speed variation, (b) corresponding influences of subjective factors, and (c) a similar scalp distribution with the exception that the BP was much more lateralized. In contrast, no such relationships were found between early CNV and BP.


A CNV rebound effect.

A CNV rebound effect. Fifty normal volunteers were tested in two conditions: (1) a constant-foreperiod reaction time situation consisting of a flash-tone-key press sequence (control trials); (2) a '50%-letters' condition, in which two types of trials occurred randomly--no letters trials, which were identical to control trials, and letters trials, which were similar to control trials but also involved the presentation of four auditory letters within the flash-tone interval as part of a short-term memory task. Compared to control trials, CNV amplitude showed a pattern of reduction in letters trials accompanied by slower reaction times to tone (CNV distraction effect). Compared to control trials, CNV amplitude showed an unexpected supranormal increase in no-letters trials. The CNV rebound effect observed in no-letters trials was interpreted as reflecting a switching of attention from the divided attention set intrinsic to letters trials (listening for letters and preparing for response to tone) to an undivided attention set in no-letters trials (simply preparing for response to tone). The CNV rebound effect, which is diminished in aging individuals and absent in psychosurgery patients, appears to represent a non-invasive technique of possible value in assessing pathophysiology of human brain functioning.


Hippocampal EEG and behaviour in dog. I. Hippocampal EEG correlates of gross motor behaviour. It was shown that rewarding spectral shifts (i.e. increase in amplitude or peak frequency of the hippocampal EEG) causes a solitary dog to show increased motor behaviour. Rewarded spectral shifts concurred with a variety of behavioural transitions. It was found that statistically significant modulations occur in the spectral properties of the hippocampal EEG correlated with: (1) the transition from walking to standing; (2) the transition from standing while eating to walking away from the food dish; (3) the increase in speed of a walking dog, caused by rewarding the animal; and with (4) each head movement in a learned series of head movements. Thus behavioural transitions to a more active state are accompanied by an increase of amplitude, frequency and rhythmicity in the theta band of the hippocampal EEG; behavioural transitions to a less active state show the inverse relationship with the hippocampal EEG. A close relationship between modulations of the dog's hippocampal EEG activity and elementary motor acts is stressed. The hypothesis is put forward that the spectral properties of the hippocampal EEG reflect the degree to which a number of motor and sensory structures in the limbic midbrain and brain stem are active.


Hippocampal EEG and behaviour in dog. II. Hippocampal EEG correlates with elementary motor acts. A positive correlation has been shown between the speed of forced stepping on a conveyor belt and the amplitude and frequency of the concomitant hippocampal EEG. Significant modulation in the spectral properties of the dog's hippocampal EEG has been found in relation to 3 elementary motor acts: stepping, respiratory movements and a reflex movement in reaction to linear acceleration of the animal. The findings support the idea that within a certain experimental situation the hippocampal EEG reflects the intensity of motor behaviour in a non-specific but predictable way. However, some experimental results indicate that sensory inputs may modulate the hippocampal EEG as well.


Hippocampal EEG and behaviour in dog. III. Hippocampal EEG correlates of stimulus-response tasks and of sexual behaviour. A dog was trained to perform a spatial sound discrimination. The hippocampal EEG correlates and the movement correlates of correct trials were compared with those of incorrect trials and of 'pressings in between'. Correct and wrong responses on a place learning task were compared both with respect to the hippocampal EEG correlates and to the motor behaviour. Where significant differences in EEG correlates were found, the motor behaviour differed significantly as well. The same was found for 2 behavioral states with different motor behavioural qualities which occurred during copulation. The data support the hypothesis that the spectral properties of the hippocampal EEG reflect in a predictable but non-specific way the intensity of motor behaviour. They question the postulated correlations between hippocampal EEG and 'internal processes', on the ground that unambiguous experimental verification of such hypothesis appears to be very difficult.


Long duration EEG studies in the case of a psychotic child. Three biotelemetric examinations and a whole night sleep recording were carried out in an 8-year-old child whose behaviour alternated between excitation and autism with stereotypes. The EEG showed 5 c/sec temporo-parietal sharp wave discharges lasting from 1 sec to 20 min. These discharges were at times unilateral and predominantly right sided, at other times bilateral, without any clinical sign of epilepsy. The chronological distribution of right, left and bilateral discharges during the successive 1 min epochs was computed and related to corresponding 'behavioural states' of the child. The paroxysmal discharges predominated when the child was awake but not involved in any relational activity; during sleep, they mostly appeared during light NREM sleep (stage I) and paradoxical sleep. The significance of these paroxysmal discharges is discussed in relation to stereotyped behaviour, vigilance and early disorganization of biological rhythms.


Off-response: its clinical incidence in very young children. Off-responses to repetitive photic stimulation may be of various shapes. In particular, very young children with respiratory distress showed a typical off-response. This reaction is rather peculiar; it consists of a triphasic, very sharp wave followed by a depolarization of longer duration. The latency is about 200 msec. This off-response seems to be the reaction of an immature brain.


Aminopyridine-induced seizure activity.

Aminopyridine-induced seizure activity. Typical seizure activity can be induced by applying 3-aminopyridine to the surface of the cat cortex. The well known characteristics of epileptiform discharges were readily observed by simultaneous recording from both the surface and deeper layers.


Interference suppression for EEG recording during open heart surgery. A device for recording the EEG during open heart surgery is described. It differs from most standard equipment in two ways. First, the input circuit is completely floating from earth and will withstand 500 V DC. Second, radiofrequency (RF) shielding and filtering permits continuous recording of the EEG during electro-surgery in the operating room. The almost undisturbed recording permits on-line continuous EEG monitoring by means of quantitative signal analysis methods.


A reflex hammer for accurate measurement of reflex latency. A hammer equipped with a piezo-electric crystal is suitable to measure fast tendon jerk latencies more accurately than a hammer equipped with a mechanical switching device. Measurements show that the hammer supplied with a piezo-electric crystal gives a pulse within 50 musec--at least 10 times faster than hammers supplied with a mechanical switch--which is negligible in comparison with the latency of any reflex response.


Differential arousal response to gustatory stimuli in the awake rabbit. ECoG arousal response as elicited by deionized water and by several concentrations of sweet, salty, sour and bitter tasting substances, all applied intraorally, were studied in the awake restrained rabbit. The study was carried out on 17 chronic preparations of adult male animals (2.6 kg average body weight). Water as a stimulant was presented in 60 trials and tastants across qualities and concentrations in 245 trials. Arousal was quantitatively characterized by its duration, frequency increment and amplitude decrement as compared to prestimulus conditions. Arousal induced by tastants was compared to that induced by water. Water and tastants induced arousals differentiable by the parameters measured. Further, most tastants produced a dose-dependent response. Comparison of ECoG and behavioral data clearly indicate that tastants inducing behavioral aversion also produce an arousal which significantly differs from response to water while behavioral preference was found not to show similar correspondence with ECoG data. The possibility of using arousal as an objective indicator for taste aversion is discussed.


Visual and computer-assisted assessment of the EEG in epilepsy of late onset. A study was made of 275 patients presenting with suspected epilepsy after the age of 20 years. In 122 it was concluded that the attacks were non-epileptic. In 60 others cerebral pathology was found. If the EEG was visibly abnormal the risk of cerebral pathology was 8 times greater than when the record was normal. The EEGs were also assessed by an automatic pattern recognition technique, which classified them as abnormal by reference to a control population of 300 volunteers. 90% of EEGs from patients with pathology were classified as abnormal and, conversely, 86% of patients with abnormal records (as assessed by the automatic analysis) had pathology.


Monosynaptic spinal reflexes elicited at various phases of the EEG alpha cycle. Relationships between the phase of EEG alpha waves and motor activities have been reported in the literature. In this study such a relation was investigated for electrically or mechanically evoked monosynaptic reflexes in the soleus muscle of normal humans. EEG alpha activity, derived from electrodes widespread over the ipsilateral and contralateral hemispheres, was tested but no relationships between alpha phase and reflex amplitudes were found.


A 200-point analog computer of average transients for electrophysiological measurements. A 200-point computer of average transients uses capacitors as the memory devices and MOS-FET switches. The averaged wave form is stored exponentially and the memory decays exponentially when that input is removed. The memory exponential time constant (i.e. the number of sweeps averaged) can be varied with one resistor. Read-out to an oscilloscope occurs simultaneously with read-in of each new signal. This linear circuit computes a highly accurate average, even though 10% components are used. It is more cost-effective than commercial digital averagers for many applications and can average evoked potentials, field potentials, weak single units and intracellularly recorded postsynaptic potentials.


System for studying the delta rhythm during sleep and its topographical amplitude distribution. An analogue system of processing all-night sleep EEG records which leads to the representation of sleep cycles by the continuous variation of the amplitude parameter in a given frequency band is described. The curves obtained are analogous to those resulting from more sophisticated computerized analyses. The cycles which they outline are in good concordance with those of the classic hypnogram. Moreover, the simplicity and the rapidity of the processing easily allow its application to multiple EEG channels. A topographical discrimination of the amplitude parameter during sleep was observed in normal subjecttion. The results obtained are illustrated in the case of a normal child and a young normal adult.


Frequency-following responses in primary auditory and reticular formation structures. The responses of the cat brain to tonal stimuli were recorded from the inferior colliculus, medial geniculate, reticular formation and the far field. The response consisted of an onset component and a frequency-following response (FFR) component in the inferior colliculus (IC) and the far field. In contrast to previous work, the FFR was also observed in the reticular formation. The response in the reticular formation was abolished at lower doses of pentobarbital and at lower relative intensities of masking than that in the IC and far field. The amplitude of the FFR increased and the latency decreased with progressive ventral movement of the electrode through the IC. The onset component of the response in IC was more easily masked than the FFR component, while the FFR component was depressed to a somewhat greater extent by pentobarbital administration. These findings suggest that the different components of the response to tonal stimuli are generated by different mechanisms.


Amplitude of evoked potentials and degree of event-related desynchronization (ERD) during photic stimulation. The variations in amplitude of visual evoked potentials (VEPs) and parallel changes in amount of event-related desynchronization (ERD) of the rhythmic activity within the alpha band were studied in central derivations of scalp EEG, in 10 normal subjects. Two methods were used to estimate the amplitude of VEPs in small groups of 10 responses: (1) inverse and matched filtering techniques; (2) two-way rank analysis of variance by the Friedman test. The two methods gave similar results and two groups, statistically different, emerged. The first, with large VEP amplitude, having at the same time large ERD, and the second, with small VEP amplitude and small ERD.


Spinal cord seizures elicited by high pressures of helium. Rats with complete spinal transections were compressed in helium-oxygen to 120 bars. Tremors and increased EMG activity in limbs rostral as well as caudal to the lesions were observed beginning at 30 bars. Spinal seizures occurred at 95 bars, similar to cortical seizure thresholds of intact rats. Denervated limbs remained flaccid throughout the dives. No rostro-caudal progression of symptoms was evident in normal animals, but fluctuation of symptoms with increasing pressure was frequently observed. These findings are consistent with the hypothesis that the effects of pressure on aggregates of neurons exceed those on isolated components.


Hippocampal evoked potentials and EEG changes during classical conditioning in the rat. Hippocampal evoked potentials (EPs) and EEG responses were studied in rats, using a classical conditioning paradigm (water, US), with a spatially discontiguous CS-US arrangement in order to separate the CS and goal-related responses. In early training, when the orienting score was high, the tone CS, instead of eliciting a definite EP, usually reset hippocampal theta activity in phase, i.e. theta rhythm became time-locked to CS. With further training, orienting activity (ORI) decreased to the preconditioning level, and this was associated with the recurrence of short-latency and high voltage hippocampal EPs, similar to those observed during habituation. This high voltage EP predicted that the animal would not orient any more towards CS. This correlation was confirmed by behavioural (satiation, shock US) and by pharmacological (scopolamine HBr, 2 mg/kg) treatments, all of which reduced the ORI score. Hippocampal EEGs also showed characteristic changes during conditioning. ORI towards CS was accompanied by higher frequency spectral peaks (9 c/sec) than response to US (7--8 c/sec). This correlation was seen both across sessions and within trials. We conclude that the above changes are related to orienting, attentional factors rather than to movement-related variables.


[Results of long-lasting drug intake on child development; clinical and electrophysiological study during drug withdrawal]. The case of a child under continuous anticonvulsant medication, especially barbiturate, since the age of 8 months for atypical seizures is reported. Medication was withdrawn when the child was 7.7 years old. The child was then under care in a Day Hospital with an autistic-like syndrome associated with important disturbances of sleep-waking regulation, complete learning incapability and major EEG abnormalities. The EEG paroxysmal discharges observed in the waking and all-night sleep records gradually decreased and then disappeared as the withdrawal was pursued over a period of several months. During the same period, the child's behaviour markedly improved and his sleep disturbances disappeared. The possibility of iatrogenic effects of early and continuous anti-convulsant therapies is discussed, even though the drug plasma levels remain within ranges generally considered as non-toxic.


'alpha pattern coma' following cerebral anoxia. In 30 patients, who were all comatose as a result of cerebral anoxia after cardiac arrest, at least one EEG with activity in the alpha frequency range was recorded. Regionally the activity of the above mentioned characteristic was often diffusely distributed or most pronounced occipitally, whereas a tendency to affect other regions was rarely observed. In 50% of the patients, where more than one EEG was recorded, the 'alpha' rhythm was still present in the following record. Only one of the patients survived, and even so, with considerable mental defects. In 4 patients the level of consciousness improved, but 3 of them never reached a definite level of cortical function and died as a result of cerebral anoxia.


Kinetic complexity of nuclear poly(A)-containing RNA in normal and regenerating rat liver. Poly(A)-containing RNA isolated from liver nuclei of untreated rats and 3 h or 12 h after partial hepatectomy or sham operation was hybridized to the complementary DNAs (cDNAs). In the homologous reactions two major components could be seen. When compared to normal liver, the complexity  of the least abundant class was lower in nuclei from livers 3 h after partial hepatectomy and was higher in those isolated 12 h after operation. The heterologous reactions revealed an increase of some abundant poly(A)-containing sequences and a loss or dilution of rare sequences 3 h after operation. The latter effect was not specific to the regeneration process but occurred after laparotomy as well. 12 h after partial hepatectomy, however, about 10% new poly(A)-containing sequences were detected, corresponding to about 5000 molecules of 4500 nucleotides length, which are unique to regenerating nuclei.


Interaction of vasoactive intestinal peptide with isolated intestinal epithelial cells from rat. 2. Characterization and structural requirements of the stimulatory effect of vasoactive intestinal peptide on production of adenosine 3':5'-monophosphate. Porcine vasoactive intestinal peptide stimulated adenosine 3':5'-monophosphate (cyclic AMP) production in rat intestinal epithelial cells. The stimulation was dependent on time and temperature and was potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Under optimal conditions (at 15 degrees C, with 0.2 mM 3-isobutyl-1-methylaxanthine, at a cell concentration up to 18 microgram DNA/ml), the cyclic AMP production produced by vasoactive intestinal peptide was constant for 10 min and stopped after 15 min incubation, at either low (1 nM) or high (30 nM) concentration of the peptide. This plateau effect was demonstrated not to be due to an inactivation of vasoactive intestinal peptide in the medium nor to an alteration of receptors for the peptide. Cyclic AMP production was sensitive to a concentration as low as 0.1 nM vasoactive intestinal peptide. Maximal stimulation of cyclic AMP levels by vasoactive intestinal peptide was observed with 30 nM vasoactive intestinal peptide and represented an 11-fold increased above basal. The dorse-response curve was monophasic with a Km of 2.3 x 10(-9) M. No cooperative effects were detected by Hill analysis. The positive non-linear relationship observed between stimulation of cyclic AMP production and occupancy of binding site was not time-dependent as indicated by experiments performed after 15, 45 and 120 min incubation. Maximal and half-maximal responses were obtained at about 70% and 7% occupation of binding sites, respectively. Chicken vasoactive intestinal peptide and porcine secretin were agonists of porcine vasoactive intestinal peptide with a 6-times and a 120-times lower potency, respectively. Among secretin analogs that were found to have low affinity for vasoactive intestinal peptide binding sites, [4-alanine, 5-valine]secretin, that resembles vasoactive intestinal peptide at the first seven amino acids at the N-terminal end, was a partial agonist of vasoactive peptide at the first seven amino acids at the N-terminal end, was a partial agonist of vasoactive intestinal peptide and others failed to stimulate cyclic AMP production. Glucagon (10microM), gastric inhibitory peptide (0.1 microM), substance, P, neurotensin, octapeptide of cholecystokinin, bovine pancreatic polypeptide, human gastrin I with leucine at residue 15, Leu-enkephalinand somatostatin (1 microM) did not alter cyclicAMP levels. Non-peptide mediators such as dopamine, serotonin, acetylcholine and histamine, tested at 10 microM, were also ineffective. Prostaglandins E2, E1 and isoproterenol, tested at 10 microM, induced an increase of cyclic AMP levels above basal but were 9.5, 13.7 and 17.5 times less efficient than vasoactive intestinal peptide, respectively. Thus vasoactive intestinal peptide is a unique stimulus of cyclic AMP production in rat intestinal epithelial cells.


Relative effectiveness of spinal cord and purified myelin basic protein in producing resistance to experimental allergic encephalomyelitis. Isolated myelin basic protein (MBP) was less effective than an equivalent amount of spinal cord in inducing protection against experimental allergic encephalomyelitis produced by a challenge of either cord, purified myelin or MBP. Complete protection was only obtained when an MBP challenge was preceded by spinal cord treatment. There was a 100% incidence of disease in the guinea pigs pretreated with MBP before challenge with spinal cord or myelin, but the onset was delayed by 3--4 weeks and the disease was less severe than in the controls. Recurrent disease was seen in some control and pretreated animals challenged with spinal cord but not in animals challenged with MBP.


Termination of natural tolerance to alpha-foetoprotein in rats: study of cell-mediated immunity in the macrophage migration inhibition test. Immunization of rats with mouse alpha-foetoprotein has been earlier shown to induce the antibody response to self AFP or rats. In this work a single injection of AFPm resulted in termination of natural tolerance of effector T-cells to AFPr, as shown by the macrophage migration inhibition test using peritoneal exudate cells from immunized animals. A significant reaction was elicited by both AFPm and AFPr in the course of primary, secondary and third immunization with AFPm. Pronounced MMI reaction to AFPm and AFPr has developed when AFPr was used as a booster antigen after primary injection with AFPm. Both the kinetics and magnitude of cell-mediated response to heterologous and self AFP injected either in CFA or without it were studied by the MMI test. T-cells of immune PEC were demonstrated by T-B separation to be responsible for MMI elicited by AFPm and AFPr.


IUDs--update on safety, effectiveness, and research. After nearly two decades of use, the IUD remains "a generally safe, effective and useful form of birth control" (337). With fewer than six pregnancies per 100 women-years of use and fewer than ten deaths per one million women-years of use, according to a comprehensive new review by the United States Food and Drug Administration, the IUD has an important place in modern family planning programs.


The effect of O-betahydroxyethyl-rutosides (HR) on the number of platelet-leukocyte aggregates in patients with occlusive arterial disease. The diagnostic value and the effect of the therapy on the number and kind of platelet-leukocyte aggregates in 68 patients with arteriosclerosis obliterans of the lower limbs were investigated. The modified SILBERGLEIT'S method was used. 8 types of aggregates were found. The means number of aggregates in 20 healthy subjects was 8.2 but in 46 patients suffering from obliterative arteriosclerosis of the lower limbs this number was significantly higher, i.e. about 62. A significant decrease in the number of platelet-leukocyte aggregates in the group of 14 patients receiving HR orally 1800 mg daily and 16 patients receiving HR intravenously 2000 mg daily was found. In 16 persons a lower HR dose (orally 900 mg daily and intravenously 500 mg daily) did not influence the number of rosettes. In 22 patients receiving nicotinic acid (orally 900 mg daily, intramuscularly 600 mg daily) no significant changes in the number of rosettes was observed.


Fractionation of outdated freeze-dried plasma: a comparative study of cold- and heat-ethanol fractionation procedures. In a comparative study a total volume of 1435 kg outdated freeze-dried plasma, equivalent to approx. 200,000 kg liquid plasma, was fractionated into albumin (20%): about 30% of the total plasma volume was fractionated following the cold-ethanol procedure and about 70% following the heat-ethanol method. Average albumin recovery following cold-ethanol preparation was 47% of the albumin originally present in the freeze-dried plasma (= 50% of total protein); following heat-ethanol fractionation, 71%. Gelfiltration of heat-ethanol albumin showed a main peak (= 93%) representing albumin monomers and one slightly faster component (= 7%) representing albumin dimers. Gelfiltration of cold-ethanol isolated albumin on the other hand showed four peaks: albumin monomers (= 60%), albumin dimers (= 15%), and two other peaks representing higher molecular weight molecules (= 25%). Hemoglobin present in the reconstituted plasma was reduced about five-fold in the cold-ethanol product and about ten-fold in the heat-ethanol albumin. Stability tests of both products did not differ from equivalent products isolated from normal human plasma. Besides albumin, immunoglobulins may be isolated as Cohn fraction II-III prior to the heating procedure without significant albumin loss.


[Effect of procaine on the loss of erythrocyte phospholipids during blood preservation in ACD-AG-stabilizer]. The phospholipid changes of erythrocytes were investigated following the storage under blood bank conditions up to 42 days (ACD-AG-stabilisator) without and with addition of procaine (25 mM). The phospholipid loss of erythrocytes is described as two-step occurrence. The rapid decrease in the first three days is followed by a further loss up to the end of the storage period. The concomitant increase of phospholipid fractions of supernatant shows that the erythrocyte membranes lose their phospholipids mainly by a passive way. For the further loss of phospholipids the action of a phospholipase A is adopted. The addition of procaine hinders strongly the phospholipid loss of erythrocytes. The clinical importance of these procaine action is shortly discussed.


[Spontaneous rosette forming, Fc and complement receptor bearing lymphocytes in pediatric diseases]. Investigations with lymphocyte subpopulations were made in 51 children aged from 1-14 years with infections of the upper airways, with acute leukaemias, and other malignant diseases. T-lymphocytes were registered by means of the spontaneous rosette test. The attempt of proving B-lymphocytes was made by means of an EAC test with human erythrocytes, anti-D-immunoglobulins and human complement. The results were compared with those obtained by an EAC test with sheep erythrocytes, sheep haemolysin and mice complement and the significance of complement discussed.


Effect of radiotherapy on the neutrophil and the lymphocyte enzymatic equipment and serum immunoglobulins in patients with cancer of the larynx. In 30 patients with cancer of the larynx, aged 40 to 70 years, treated by radiotherapy 6 to 9 years ago the decreased activity of neutrophil beta-glucuronidase and N-acetyl-beta-glucosaminidase accompanied by a decrease of absolute count of enzyme-positive cells was noted. Numbers of acid phosphatase-positive neutrophils were also decreased. Moderate increase of the neutrophil alkaline phosphatase activity and of numbers of enzyme-positive cells was another observed feature. The main finding in lymphocytes of the patients consisted in the appearance of cells exhibiting diffusion of lysosomal enzymes, especially of beta-glucuronidase, N-acetyl-beta-glucosaminidase and to a lesser degree of acid phosphatase into the cell cytoplasm. Moderate increase of immunoglobulin level, especially that of IgA, reflected probably the immunologic mobilization of patients.


Extramedullary haematopoiesis in thrombotic thrombocytopenic purpura. Extramedullary hematopoiesis was detected in routine sections of spleen and liver from two patients with thrombotic thrombocytopenic purpura (TTP). In patients with other types of hemolytic anemia and in normal persons, extramedullary hematopoiesis was not found in spleen or liver. The results of this study raise the possibility that TTP may fit within the myeloproliferative category, perhaps representing an acute variant of Di-Guglielmo Syndrome.


[Compatibility of antihuman lymphocyte globulin (AHLG). Possible side effects and complications]. The results in the antihuman lymphocytic globulines (AHLG) therapy of 25 patients with predominantly haematological and neurological diseases are reported. Extent and scope of the side-effects observed are discussed. A careful clinical, clinico-chemical and immunological observation of the patients during the AHLG therapy is indispensable for performing this biological immunosuppression and a strict selection of patients is also required. Under these conditions there are no higher risk and responsibility in an AHLG therapy than in other intensive kinds of therapy.


[Use of antilymphocyte globulin in autoimmune nervous system diseases]. The pathogenetic bases for the indication of immunosuppression in multiple sclerosis are represented in a survey, rested upon experiences in the clinical compatability test of AHLG Dessau. The knowledge gained in animal experiments and epidemiology in recent years is considered and problems of membrane, slow-virus hypothesis, genetic problems and changes of immunoglobulins and lymphocytes are critically referred to.


Electroimmunoassay of factor IX in patients with liver damage and vitamin K unresponsive coagulation disorder. Factor IX antigen and activity were assayed in a group of patients with liver disease and in a group of patients in coumarin therapy. In patients with liver disease there was a similar decrease in activity and antigen. On the other hand factor IX activity is decreased in coumarin treatment with factor IX antigen remaining normal. Factor IX electrophoretic mobility in liver disease is normal.


[Determination of selected coagulation parameters in induced abortion by means of 15-methyl-PGF2 alpha]. There were accomplished investigations about changes of bleeding and recalcification time, platelet count, levels of heat-fibrin, prothrombin, partial thromboplastin time, platelet adhesiveness and heparinocytes at 10 women during induction of therapeutic abortion by use of intramuscular injections of 15-methyl-PGF2 alpha in the first and second trimester of pregnancy. The studies were performed before treatment, 30 minutes, 4 and 8 hours after beginning 15-methyl-PGF2 alpha-administration, 2 hours after expulsion of product of conception  and 24 hours after first injection. The following investigations showed statistical significant changes: Prothrombin decreased during treatment with 15-methyl-PGF2 alpha and did not obtain the starting value 24 hours after first injection. Platelet count showed an equal attitude. The heparinocytes showed a continuous falling off up to 2 hours after termination the pregnancy. A significant ascent was noticed 24 hours after first investigation. The results of studies did not indicate a strong injury of coagulation system. They support the positive estimate for induction of therapeutic abortion with 15-methyl-PGF2 alpha in the first and second trimester of pregnancy.


[Activation by means of various adsorbents. (Contribution to the mechanism of contact activation of the blood coagulation process)]. 20 different adsorbing substances were examined for the purpose of determining physico-chemical parameters influencing the contact activation in the partial thromboplastin time (PTT). In the course of these examinations the prerequisites for the process under way were found to exist in a low adsorbing activity of the substance used as a surface and in the reversibility of adsorption. The effect activating the contact will depend on surface conditions and to a lesser degree on its size. An even crystal structure and the size of particles will have a positive influence on the surface properties and thus on the effect activating the contact.


[The protease inhibitor potential in newborns with respiratory distress syndrome]. In 70 newborns with respiratory distress syndrome (RDS) and in roughly the same number of eutrophic mature newborns the total antiplasmin, progressive antithrombin and alpha 2-macroglobulin was determined, the latter in an enzymatical as well as immunochemical way. In healthy mature newborns the progressive antithrombin was somewhat below the level of adults, alpha 2-macroglobulin was above it in both methods and total antiplasmin within it. All parameters of protease inhibitory capacity were significantly lowered in newborns with RDS. Smaller values could be found in patients with bleedings and in those who died later on. Even in those patients with a birth weight under 2,000 g there was a tendency to lower values which can only be partially due to the specificity of development of inhibitors. Progressive antithrombin, total antiplasmin and alpha 2-macroglobulin determined enzymatically are correlated in newborns with RDS jointly and with numerous other parameters of the coagulation system. These relations point to the fact that all components are included in the same consumption process, viz. in the process of disseminated intravascular coagulation. Alpha 2-macroglobulin values determined immunochemically do not correlate with coagulation parameters determined enzymatically as well as with other parameters. They lay partially above or below those determined enzymatically. This behaviour can only be explained by a partial enzyme complex binding of alpha 2-macroglobulin in newborns with RDS.


Some aspects of order and symbolism in schizophrenia. Developing out Rümke's term of "PraecoxGefühl", it is described that the schizophrenic disorder in his way of being is the fundamental underlying reason for dissociation of his thoughts and feelings. This consequently leads to a distortion in his system of sign recognition and the meaning attached to the different semantic and syntactic levels. By means of the "Wahnarbeit" and other mechanisms the schizophrenic tries to build another order in which he can feel more at ease with his overwhelming experiences. The conceptualization of his thoughts is performed by using a "principle of symmetry"--attaching the meaning of one perceived object (I) of reality to another conceptualized object (II). Very often we are unable to understand the individualistic nature of schizophrenic symbolization because of this mechanism.


[Diagnosis and therapy of hypotensive circulatory disorders in general practice. Experiences with Gutron using the Thulesius-diagram for diagnosis and supervision of therapy]. The alpha-adrenergic stimulating agent Gutron, given orally for 10 days, induced a subjective and objective improvement of orthostatic disorders in a total of 114 hypotensive patients in 7 general practices. The use of the Thulesius diagram in diagnosing orthostatic disorders further improved the rate of success and diminished the frequency of side effects distinctly. Gutron is indicated in all patients with a systolic blood pressure fall of at least 10 mmHg and a concomitant rise in heart rate when changing from lying to standing position (asympathicotonic and sympathicotonic hypotension).


[Tetanus antibodies in conventional gamma globulin preparations]. Different specimens of one of the most common polyvalent immunoglobulin-preparations in the Federal Republic of Germany contain tetanus-antitoxin with an average titer of 40 I.E.Hml. The injection of 5 ml of this conventional gammaglobulin effects in an adult person a titer of ca. 0,75 I.E. Tetanus-antitoxin/ml serum (minimal protectin level = 0,01 I.E./ml). The prophylactic application of 5 ml of the conventional IgG-preparation (gammaglobulin) in travelers against epidemic hepatitis results in a protection against tetanus, too, at least for 3-4 weeks.


[The problem of hepatic dysfunction of the diagnosis of hypernephroid kidney carcinomas (Stauffer syndrome)]. In 43 patients with histologically proved hypernephroid kidney cancer evaluation of the electrophoretic results, serum alkaline phosphatase, thromboplastin time (Quick's time) and bromthalein retention (n = 10) was carried out. As a control group the serum values of 10 patients with clinical tentative diagnosis of hypernephroid kidney cancer were checked; in this group operation and histological examination showed no kidney tumor. Only in one patient we found the typical constellation with elevated alkaline phosphatase, diminished albumin, elevated alpha-2 globuline fraction, and decreased thromboplastin time. 10 patients with histologically proved hypernephroid kidney cancer (nephrectomy) did not show any hepatic dysfunctions. Concerning the laboratory findings there was no difference between the two groups. In case of hepatic dysfunctions of unknown etiology a liver punction should be carried out for histologically examination. The cause of hepatic dysfunction (Stauffer syndrome) in cases of hypernephroid kidney cancer are discussed.


You are what you wear.

You are what you wear. Uniforms and professional roles are frequently tied in the minds of both staff and patient, so it may be advisable to return to greater use of uniforms by hospital professional staffs.


Correlated inhibition of ribosomal RNA synthesis and silver staining by actinomycin D. Preferential inhibition of the synthesis of ribosomal RNA by low doses of actinomycin D was used to investigate the quantitative relationship between the intensity of silver staining of nucleoli and the rate of RNA-synthesis. The two parameters were found to be strongly correlated in human diploid fibroblasts.


Nucleolus organiser regions on mitotic and meiotic chromosomes from infertile males investigated using a specific silver stain. Mitotic preparations from 30 subfertile males and meiotic preparations from 3 normal and 2 subfertile males were examined by means of the Ag-I technique of Bloom and Goodpasture (1976) to reveal nucleolus organiser regions (NORs). In the mitotic preparations, each subject was found to have a characteristic number of Ag-positive NORs per cell, within a range of 6--10. Analysis of satellite associations showed that the mean number of satellite associations per cell was related to the modal number of Ag-positive NORs for each subject. In the meiotic preparations, silver deposition was observed throughout meiotic prophase, but disappeared totally during diakinesis and metaphase II. It was seen again in early spermatids, and disappeared again as nuclear elongation took place. This pattern was observed in both normal and subfertile subjects, and may provide indirect evidence for the activation of rRNA genes during spermatogenesis.


Serum protein polymorphisms in a village community from the Gambia, West Africa (Hp, Tf, and Gc). Serum samples from 857 inhabitants of the village of Keneba, The Gambia, West Africa, were examined by means of polyacrylamide gel electrophoresis. In 203 cases no haptoglobin could be detected, whilst in the remaining 654 samples the three common haptoglobin phenotypes were found with gene frequencies of 0.651 (Hp1) and 0.349 (Hp2). The D1 transferrin variant gene was found with a frequency of 0.025. In the serum Gc system the fast variant Gc-Ab was detected, the gene frequencies being: Gc1, 0.943; Gc2, 0.044; and GcAb, 0.013.


Pathological features of cantharidin-induced toxic cardiomyopathy: lack of correlation between electron-microscopic and histopathologic myocardial damage. Electron-microscopic evidence of the cardiotoxic effects of cantharidin administered to rabbits was observed. No correlation was found between the electron-microscopic changes and the light-microscopic features as assessed by special histological stains. The reasons for this are discussed.


Cytochemical analysis on a case of familial 17ps. Chromosome 17ps was identified in the mother and daughter but not the father of a normal family with no history of congenital abnormality. In addition to G-band and Ag-NOR staining, previously used to study this abnormality, we applied N-band and C-band techniques. Our results showed that 17ps has no demonstrable ribosomal cistron or constitutive heterochromatin.


Nucleolar organizing regions of human chromosomes. Silver-stained cells from 49 parents with a history of several abortions were compared with cells from 35 parents with normal liveborn children. The modal and mean number of silver-stained NORs (Ag-NORs) observed on D- or G-group chromosomes was similar in both groups and between males and females. Ag-NORs were randomly distributed on all five acrocentric pairs. The distribution and size of Ag-NORs within an individual was not random and was fairly consistent from cell to cell. The mean number of associations per cell was similar in both males and females of the abortion group and was less than the number of associations in controls. The probability of D- or G-group chromosomes being associated was near the expected probability of 0.6 for D-association and 0.4 for G-association. The frequency of association of any chromosome combination did not differ statistically from the expected values, though the number of associations, 15/22, was higher than expected.


Localization of the nucleolar organizer by computer-aided analysis of a variant no. 21 in a human isolate. A variant chromosome no. 21 consisting of two stalks and two satellites in tandem was detected during a survey of a human isolate. The variant segregated in three generations of a large kindred. One male had the variant no. 21, a metacentric Y, and a 47,XXY complement; however, no other evidence of chromosomal nondisjunction was found. Computer-aided analysis of sequentially stained variant no. 21 chromosomes indicated that silver-stained material corresponded to the proximal stalk region (as defined by Giemsa), but often covered both the distal stalk and satellite (also as defined by Giemsa). These data support the hypothesis that human nucleolar organizers are localized to the stalks of acrocentric chromosomes.


[Intravascular persistence, tissue storage and excretion of hydroxyethyl starch (HAS)]. Hydroxyethyl starch is a derivative of amylopectin, the branched glycogen-like alpha-1,4-glucose polymer, the amylase hydrolysis of which is retarded by hydroxyethylation. If 70 to 90 per cent of the glucose polymer units contain hydroxyethyl groups, the intravascular persistence and urinary excretion of hydroxyethyl starch of a molecular weight of 435,000 is similar to that of Dextran 70. Hydroxyethyl starch and Dextran 70 are stored briefly in reticuloendothelial and hepatic cells, and cause swelling and vacuolation of renal tubules with little alteration of renal function. Elimination of hydroxyethyl starch from sites of tissue storage is much faster than elimination of the non-metabolized polymers acacia and polyvinylpyrrolidone. The distribution and excretion kinetics of hydroxyethyl starch are thus appropriate for a plasma substitute.


Immunological and serological diversity of Neisseria gonorrhoeae: identification of new immunotypes and highly protective strains. Gonococci, irrespective of serotype or immunotype, varied significantly in their capacity to induce immunity in animal models, and in vitro serological relatedness did not always insure in vivo cross-protection. By using a serum bactericidal assay followed by in vivo cross-protection studies, new immunotypic strains which were highly protective were identified from cultures isolated in different geographical areas and from patients with various clinical manifestations. Beta-lactamase production and gonococcal immunotype did not appear as related characteristics in that certain penicillin-sensitive strains were highly effective in immunizing animals against infection with beta-lactamase producers. The findings of this study emphasize the importance of using appropriate biological tests and strains for the investigation of gonococcal immunity and vaccine development. Immunization with a combination of a few major gonococcal immunotypic immunogens may provide substantial protection against the majority of penicillin-sensitive and beta-lactamase-producing gonococci. Investigation of isolated immunotypic immunogens is in progress.


Chemical, immunochemical, and structural studies of the cross-reactive antigens of Streptococcus mutans AHT and B13. Two antigenic polysaccharides were extracted from cell walls of the cross-reactive strains Streptococcus mutans AHT (a) and S. mutans B13 (d). The antigens extracted from walls by the hot formamide method, were purified by affinity chromatography on columns containing the galactose-specific lectin from the castor bean and were found to be diheteroglycans consisting of galactose and glucose. Antigenic specificities of both the serotype-specific and the cross-reactive sites on each polymer were studied: the AHT (a) antigen is determined by D-galactose linked 1 leads to 6 to adjacent sugar, the B13 (d) antigen is determined by D-glucose similarly linked to o its neighbor, and the cross-reactive (a--d) site present on both polymers consists of D-galactose linked 1 leads to 6 to a subterminal sugar moiety. Methylation analysis revealed structural similarities between the purified polysaccharides that may reflect the nature of the cross-reactive sites and differences that may reflect the natures of the specific haptenic regions. Based on these studies, a partial hypothetical structural model is proposed.