Strand breakage by the DNA untwisting enzyme results in covalent attachment of the enzyme to DNA. Strands of DNA that have been broken by the DNA untwisting enzyme exhibit a reduced buoyant density in alkaline CsCl due to bound protein. A covalent linkage between the DNA and the enzyme was indicated by the stability of the complex in alkali (pH greaterthan 12.7), in 7 M guanidine-HCl, and at 90 degrees in 1% Sarkosyl for 5 min. The single-strand breaks generated by the enzyme are resistant to exonuclease III, indicating that the protein is attached to one of the ends of the broken strands. The free end of the broken strand bears a 5'-hydroxyl group, indicating attachment of the protein to the 3'-phosphoryl terminus. A nucleotide-peptide linkage involving a phosphoamide bond is unlikely since the complex is resistant to 3.5 M hydroxylamine at pH 4.75.


Fundamental aspects of electron transfer: experimental verification of vibronically coupled electron tunneling. A detailed investigation of the applicability of the vibronically coupled electron tunneling theory in biomolecules can be made by a quantitative study of a weak charge-transfer optical absorption band that has been predicted by this theory. The measurement of the position, width, and molar extinction coefficient of this band is examined in the bound model system cytochrome c-Fe(CN)6 at room temperature and demonstrates that the theory is quantitatively applicable in this system. The size of the parameters measured is typical of those relevant for biological electron transfers. The comparisons lend credibility to the generality of vibronically coupled electron theory in biomolecules and its short transfer distances.


X-ray absorption edge studies on oxidized and reduced cytochrome c oxidase. The x-ray absorption edge spectra of the Cu and Fe-centers in oxidized and reduced cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase: EC 1.9.3.1) have been obtained using synchrotron radiation from the SPEAR storage ring at the Stanford Linear Accelerator Center. In addition, oxidized and reduced plastocyanin as well as a number of model copper compounds in various oxidation states were also examined. A comparison of the absorption edge fine structure of cytochrome oxidase with those of the models indicates that one of the two coopers in the oxidized protein is in the +1 oxidation state. Upon reduction of the protein with dithionite, the second copper becomes Cu(I). The shift in the Fe K-edge of cytochrome oxidase upon reduction is small (about 2 e V or 3 times 10(-19 J) and is comparable to that previously observed for the reduction of the heme iron of cytochrome c.


Electron paramagentic resonance studies of photosynthetic electron transport: photoreduction of ferredoxinand membrane-bound iron-sulfur centers. Electron paramagnetic resonance spectrometry was used to investigate, at physiological temperatures, light-induced electron transport from membrane-bound iron-sulfur components (bound ferredoxin) to soluble ferredoxin and NADP(+) in membrane fragments (from the blue-green alga, Nostoc muscorum) that had high rates of electron transport from water to NADP(+) and from an artificial electron donor, reduced dichlorophenolindophenol (DCIPH(2)) to NADP(+). Illumination at 20 degrees resulted in the photoreduction of membrane-bound iron-sulfur centers A and B. Photoreduction by water gave electron paramagnetic resonance signals of both centers A and B; photoreduction by DCIPH(2) was found to generate a strong electron paramagnetic signal of only center B. When water was the reductant, the addition and photoreduction of soluble ferredoxin generated additional signals characteristics of soluble ferredoxin without causing a decrease in the amplitude of the signals due to centers A and B. The further addition of NADP(+) (and its photoreduction) greatly diminished signals due to the bound iron-sulfur centers and to soluble ferredoxin. An outflow of electrons from center B to soluble ferredoxin and NADP(+) was particularly pronounced when DCIPH(2) was the reductant. These observations provide the first evidence for a light-induced electron transport between membrane-bound iron-sulfur centers and ferredoxin-NADP(+). The relationship of these observations to current concepts of photosynthetic electron transport is discussed.


Glucose depletion accounts for the induction of two transformation-sensitive membrane proteinsin Rous sarcoma virus-transformed chick embryo fibroblasts. Chick embryo fibroblasts transformed by Rous sarcoma virus have an increased content of two membrane proteins of molecular weights 78,000 and 95,000. The increased content of the 95,000-dalton protein and the principal increase in the content of the 78,000-dalton protein are not an early consequence of cell transformation but instead are secondary to the rapid depletion of glucose  from the growth medium of transformed cells. When glucose is maintained at high levels in the growth medium of transformed cells, the synthesis of the 95,000-dalton protein is arrested and that of the 78,000-dalton protein is markedly suppressed. Upon removal of glucose from the growth medium of normal cells, these proteins increase to levels comparable to those of transformed cells. Because the amount of these two proteins is influenced by the presence or absence of glucose, we suggest they be referred to as "glucose-regulated proteins." GRP-78 and GRP-95. These proteins may have an important role in regulating the utilization of glucose in cultured cells.


Synthesis of collagen by chondrocytes in suspension culture: modulation by calcium, 3':5'-cyclic AMP, and prostaglandins. Rabbit articular chondrocytes synthesize type II collagen [3alpha(1)(II)] in vivo and type I collagen [2alpha(1)(I).alpha(2)] in monolayer cultures. In suspension culture the nature of phenotype depends on extracellular Ca(2+). The relationship of Ca(2+) and 3':5'-cyclic AMP (cAMP) in regulation of collagen synthesis has been investigated. In suspension culture, cAMP levels of chondrocytes increase by 2- to 3-fold and then reach basal values regardless of the presence or absence of extracellular Ca(2+). The cells, however, synthesize primarily type II collagen in the absence of CaCl(2) in the medium and type I collagen in medium containing 1.8 mM CaCl(2). If CaCl(2) is added when intracellular cAMP levels are low, the phenotype is type I collagen. These observations minimize the role of cAMP as a second messenger in the chondrocyte culture system. Increasing endogenous cAMP with a phosphodiesterase inhibitor or adding exogenous dibutyryl-cAMP leads the cells to synthesize type I collagen, although this effect is significantly less pronounced if the medium contains ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA). Increased concentrations of cAMP may mobilize the intracellular calcium pools and activate the cells to switch their phenotypic expression. Prostaglandins E(2) and F(2)alpha, thought to be involved in rheumatoid arthritis and bone resorption, have no significant effect on cAMP content of chondrocytes and alter their collagen phenotype to a small extent.


Division of BALB/c mouse 3T3 and simian virus 40-transformed 3T3 cells in cellular aggregates. BALB/c mouse 3T3 cells and 3T3 cells transformed by simian virus 40 (SV40) were cultured as aggregates in agitated liquid medium. When maintained with daily medium changes, 3T3 cells incorporated [(3)H]thymidine into acid-insoluble material at a rate (1/4) that of 3T3 cells in logarithmic-phase flat cultures but 16 times that of the same cells in stationary-phase flat cultures. Similarly, SV40-transformed 3T3 cells in aggregates incorporated [(3)H]thymidine at (1/3) the rate of SV40-3T3 cells in logarithimic-phase flat culture and 14 times that of these cells in stationary-phase flat culture. Autoradiographs of aggregates of 3T3 and SV40-3T3 cells incubated for 2 hr in the presence of [(3)H]uridine and [(3)H]thymidine indicated that penetration of the nucleosides into aggregates during this period was limited to the outer four to six cell layers. Aggregates were also incubated in the presence of radiolabeled thymidine and uridine continuously for 4 days. Under these conditions, where nucleoside penetration was not limiting, 100% of the SV40-3T3 cells and 56% of the 3T3 cells incorporated [(3)H]thymidine into acid-insoluble material. The rates of cell division, cell loss, and net cell accumulation in aggregates of 3T3 and SV40-3T3 cells were measured by techniques not influenced by possible alterations in transport, pool size, or penetration. SV40-3T3 cells divided with a doubling time for the total population of 26.0 hr. The total cell number increased more slowly (doubling time of 48.3 hr) because of cell loss, which occurred with a half-time (time for 50% of the cells to be lost) of 53.3 hr. 3T3 cells in aggregates began to divide only after 3 days, then did so with a doubling time for the total population of 76.4 hr. Total cell number decreased (half-time of 26.3 hr) because this rate of cell division was exceeded by the rate of cell loss, which was constant with a half-time of 22.9 hr. The results suggest that 3T3 and SV40-3T3 cells display growth properties in aggregates consistent with their previously reported behavior in conventional flat culture: SV40-transformed 3T3 cells can proliferate under conditions of high cell density to a much greater extent than 3T3 cells can. Both cell lines, however, display an increased capacity to divide in aggregates relative to confluent flat culture, despite conditions of high cell density and absence of anchorage to an artificial solid substrate.


Cell fusion induced by herpes simplex virus is promoted and suppressed by different viral glycoproteins. Some of the factors that regulate membrane fusion resulting in polykaryocyte formationhave been investigated, using the model system of human cells infected with mutants of herpes simplex virus (HSV). One of the mutant viruses used in this study (MP) failed to produce the viral glycoprotein designated C2--a nonlethal defect that has previously been correlated with the polykaryocyte-inducing phenotype of this and other mutant strains (wild-type strains of HSV usually induce the aggregation of infected cells rather than their fusion). The other mutant virus (tsB5), a temperature-sensitive conditional-lethal mutant, failed to produce glycoprotein B2 at non-permissive temperature, whereas the synthesis of all other viral products appeared to be normal. We produced and isolated seven recombinants of MP and tsB5 that expressed both of the parental alterations in glycoprotein synthesis. All of the re-combinant viruses induced the fusion of infected cells at 34 degrees (correlated with the absence of C2 expression) but were unable to cause cell fusion at 39 degrees (correlated with the absence of C2 and of B2 expression), even after infection at multiplicities high enough to ensure that all cells in the cultures synthesized viral macromolecules. These results and studies on the dominance or recessiveness of the fusion-inducing phenotype in mixed infections provide evidence that glycoprotein B2 plays a critical role in the promotion of cell fusion and that glycoprotein C2 can act to suppress fusion.


Amyloid protein SAA is associated with high density lipoprotein from human serum. Human serums contain a protein antigenically related to protein AA, the principal protein of a major class of amyloid substance. The serum antigen, SAA, occurs mainly in a high molecular weight form, 1 to 2 X 10(5). This work shows that the bulk of the SAA sediments at density 1.12 g/cm3 and floats at density 1.21 g/cm3, as does the high density lipoprotein HDL3. SAA is associated with the apolipoproteins ApoA-I and ApoA-II. The total cholesterol:total protein ratio of the fraction with density 1.12-1.21 g/cm3 is 0.2:1, consistent with that of SAA constituent of the HDL3 fraction into low molecular weight species of the order of 13,000. The quantity of SAA may vary from 0.1% or more of the total protein of HDL3.


Specific receptors for des-Asp1-angiotensin II (("angiotensin III") in rat adrenals. The specific binding of angiotensin II and des-Asp1-angiotensin II ("angiotensin III") III") to rat adrenals was studied with the use of the tritiated peptides. The binding sites having maximal affinity for angiotensin II were characterized by an equilibrium dissociation constant of 3.3 to 5.2 X 10(-9) M. Angiotensin III was able to interact with these sites, and also with a class of sites with very high affinity, characterized by an equilibrium dissociation constant of 1 to 2 X 10(-10) M. These sites exhibited a greater affinity for the heptapeptide angiotensin III than for the octapeptide angiotensin II. These findings, together with the known potent aldosterone stimulating effect of angiotensin III and its presence in rat plasma, suggest that this heptapeptide could be the physiologically important steroidogenic angiotensin in this species.


Alteration of cellular adhesion by nerve growth factor. Nerve growth factor increases the initial rates of cell-substratum and cell-cell adhesion of sympathetic nerve cell clone PC12. It also stimulates adenosine 3':5'-cyclic monophosphate accumulation in the cells, and exogenous adenosine 3':5'-cyclic monophosphate increases cell-substratum adhesion. NGH-stimulated adhesion is energy dependent and cold-sensitive and does not require de novo protein synthesis. It is probably mediated by an effect of adenosine 3':5'-cyclic monophosphate on the plasma membrane. Stimulation of cellular adhesion may be the first step in NGF-initiated neurite outgrowth by sympathetic nerve cells.


Urinary cyclic AMP excretion by methadone subjects during gradual and acute withdrawal. Laboratory and animal investigations have supported the hypothesis that levels of cyclic AMP are stable during tolerance to narcotic drugs and increased during withdrawal. In order to test this hypothesis, serial 24-h urinary excretion of cyclic AMP by long-term methadone addicts was determined during a period of stable methadone intake, a period of gradual withdrawal, and a period of acute withdrawal. Cyclic AMP excretion during stable methadone intake is identical to that of normal control subjects. Neither gradual nor acute withdrawal appears to affect the urinary excretion of cyclic AMP. These data agree with previous reports in the literature which suggest that cyclic AMP levels are not altered during tolerance to narcotics, but do not support the hypothesis that levels of the nucleotide might be increased during withdrawal.


Effects on hypothalamic self-stimulation of drugs influencing dopaminergic neurotransmission injected into nucleus accumbens and corpus striatum of rats. The role of the nucleus accumbens septi (ACB) and corpus striatum (CPU) in self-stimulation were investigated by injecting directly or indirectly acting stimulant drugs or a dopamine-(DA)-receptor blocking agent into each site bilaterally. d-Amphetamine (68 nmol) facilitated hypothalamic self-stimulation when injected into either side. Apomorphine (40 nmol) depressed or facilitated responding, the direction and magnitude of this effect being contingent (C = 0.52) on the effect of systemic injection (0.3 mg/kg.i.p.), and correlated with the difference between the effects of d- and l-amphetamine (0.5 mg/kg i.p.) but not with injection site. Haloperidol (6.6 nmol) in either site depressed self-stimulation. Tyramine (730 nmol), an agent believed to cause noncontingent displacement of transmitter from catecholamine terminals, depressed self-stimulation when injection into CPU, but facilitated it when injected into ACB. The site-specific effects found with tyramine but not with apomorphine may have been due to release by tyramine of transmitters other than DA.


Autosomal dominant osteosclerosis.

Autosomal dominant osteosclerosis. Two cases of a craniotubular hyperostosis are presented. The radiographic features closely resemble Van Buchem disease (hyperostosis corticalis generalisata; endosteal hyperostosis, recessive type), including symmetrical and bilateral diaphyseal cortical thickening of the long and short tubular bones as well as sclerosis and thickening of the calvaria, mandible, shoulder and pelvic girdles, and thoracic cage. Unlike Van Buchem disease, no periosteal excresences are observed, alkaline phosphatase is normal, no basal foramina encroachment of the skull is present, and the genetic pattern is dominant inheritance. These cases possibly represent a separate disorder rather than a variant of Van Buchem disease.


Generalized cortical hyperostosis (Van Buchem disease): nosologic considerations. Six of 41 presumed cases of Van Buchem disease described in the literature fit uniform diagnostic criteria. Segregation analysis of these 6 cases, in addition to another the authors report, supports a recessive mode of inheritance. Genetic heterogeneity is confirmed by the demonstration of a dominantly-inherited phenotype resembling Van Buchem disease. The probable etiology is a defect in the endochrondral modulatory step regulating transformation of osteoclast to osteoblast.


Combination chemotherapy and radiotherapy in small-cell carcinoma of the lung. A combination of chemotherapy (Cytoxan, vincristine, and CCNU) and radiation therapy was used to treat 37 patients with small-cell carcinoma of the lung. There was 49% complete remission and an overall 76% objective response with an overall median survival of 12.5 months and 17 months for those showing a complete response. No serious morbidity was observed.


Autosomal dominant osteosclerosis.

Autosomal dominant osteosclerosis. Autosomal dominant osteosclerosis, an entity previously labelled by various names, is clearly separate from Van Buchem disease; Van Buchem disease exhibits autosomal recessive inheritance. The clinical manifestation of autosomal dominant osteosclerosis is a widened and deepened mandible with increased gonial angle. Radiographic manifestations include endosteal sclerosis of the neurocranium with loss of the diploë, osteosclerosis and hyperostosis of the mandible with absence of the normal antegonial notches, endosteal sclerosis of the diaphyses of long bones (including metacarpals and metatarsals), and osteosclerosis of the pelvis.


Effects of prostaglandins on rat renal adenylate cyclase-cyclic AMP systems. The effects of prostaglandin (PG) E1, E2, A1, F1alpha, F2alpha or D2 on the rat renal cortical, outer medullary and inner medullary adenylate cyclase-cyclic AMP systems were examined. While high concentrations (8X10-4M) of each prostaglandin stimulated adenylate cyclase activity in each area of the kidney, PGE1 was the only prostaglandin to stimulate at 10-7M. PGA's were the only prostaglandins tested besides PGE's which stimulated adenylate cyclase at less than 10-4M. This effect of PGA's was limited to the outer medulla. PGD2 was the least stimulatory. Observations with renal slices yielded qualitatively similar results. The PGE's were the most potent in each area with PGA's only stimulatory in the outer medulla. O2 deprivation (5% O2) lowered the slice cyclic AMP content in each area of the kidney. In the cortex and outer medulla, prostaglandin mediated increases in cyclic AMP content were either lower or absent at 5% O2 compared to 95% O2. However, in the inner medulla PGE stimulation was observed only at 5% O2 and not 95% O2. No other prostaglandins were found to increase inner medullary cyclic AMP content at 95% or 5% O2. These results illustrate that the adenylate cyclase-cyclic AMP system responds uniquely to prostaglandins in each area of the kidney. Consideration of these results along with correlative observations suggests that inner medullary produced PGE's may act as local modulators of inner medullary adenylate cyclase.


["E" rosette formation in "active" T lymphocytes: phenomenon modulated by intracellular level of cyclic AMP and GMP (author's transl)]. The rosette formation envolving the binding of sheep red blood cells (SRBC) with active T lymphocytes was activated when the lymphocytes were incubated with levamisole, acetylcholine or carbamylcholine. Similar activation was seen when to the incubation medium was added substances of glucose metabolism (lactate, fumarate or succinate) or triphosphate de adenosina--ATP. The lymphocytes incubation with aminophyline, isoproterenol or 2-4-dinitrofenol--DNP--inhibited the rosette formation. The inhibition promoted by aminophyline was reversed by levamisole, acetylcholine or carbamylcholine, but not when lactate or ATP was used. When the rosette formation inhibition was caused by DNP, the reversion was only possible by ATP and no affect occurred if guanil cyclase activators were added to the incubation medium.


[Morphological (Macro-, micro-electronoptical) changes and cytoenzyme changes after ligation of the pulmonary artery, pulmonary veins and both in dogs]. In six dogs ligature of the main pulmonary artery was performed, and in five other ligature of the pulmonary veins was carried out, while in five other animals combined simultaneous ligatures were made. Extensive infarcization was noted, of the pulmonary tissue, with an evolution toward death, in all types of ligatures. Death occured earlier in ligatures of the pulmonary veins. All the interventions were performed on the left lung, under general anesthesia, orotracheal intubation and assisted respiration. Electron-optic investigation revealed mitochondrial alterations 30 minutes after ligature of the pulmonary veins and 2 hours after that of the pulmonary arteries. The lesions were extensive in time. In the infarction areas the activity of the energetic enzymes (SDH, NADH2, G6PD, LDM) appears to be reduced, and even completly abolished. This occurs earlier when pulmonary veins are closed. On the basis of clinical and surgical data already mentioned in the literature, as well as on that of the experimental studies performed, the authors consider that ligature of the pulmonary artery, either therapeutically or due to various necessities, an intervention that is recommended by some surgeons, is not a functional type of intervention, and can even have ill-fated results, especially if the pulmonary venous circulation is also involve in the pathological process.


[Neurophysiological data on transmission and integration of nociceptive messages (author's transl)]. In this study cutaneous nociceptive messages are followed at different levels of the CNS, from the periphery to the cortex. A brief summary is given concerning the role of the fine myelinated and unmyelinated fibres which are specifically activated by noxious stimuli. A more extensive review considers the spinal mechanisms which sustain the transmission of nociceptive messages; the electrophysiological properties of interneurones located in laminae VIII, V, and I of the dorsal horn are described in detail. At the same time, the problem of the ascending projections of those cells activated by nociceptive stimuli is discussed. Particular attention is paid to the controls acting at the spinal level: segmental controls are described first and lead to discussion of the "gate control theory"; descending inhibitory controls are then discussed and their importance emphasized. The complexity of pain mechanisms at the supra-spinal level is underlined and a brief review considers the role of various bulbar, mesencephalic and thalamic structures involved in transmission of noxious messages. Among these structures, the PO group of nuclei seem to have a particular role in pain processes. Although the importance of the cortex for final integration of nociceptive messages is discussed, a brief summary is also given of investigations into the role of somatic area SII.


The agonist and antagonist properties of N-allylenkephalins. The agonist (ID 50) and antagonist (Ke) potencies of the newly synthesized N-allyl derivatives of Met5-enkephalin and Leu5-enkephalin were compared with those of their respective parent compounds on the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum. N-allyl substitution of the aminenitrogen in the Met5-enkephalin significantly decreased both the ID 50 and the Ke. In contrast, similar substitution in Leu5-enkephalin did not significantly alter the ID50, but caused an almost tenfold increase in the Ke. The results suggest that substitution on the amine-nitrogen of Leu5-enkephalin rather than Met5-enkephalin is more likely to produce potent narcotic antagonists.


An assessment of the effects of enzyme inducers on aryl hydrocarbon hydroxylase activity. The aryl hydrocarbon hydroxylase activity for control, Aroclor 1254 and FireMaster BP-6 induced hepatic microsomes was determined using 4-chlorobiphenyl, a model PCB isomer, as the substrate. The assay system was used to quantitate the amount of metabolites, conjugates and macromolecular adducts formed for the induced and control microsomes. The metabolites and conjugates were designated detoxification (D) products and the macromolecular adducts designated as toxification (T) products. From the data it was then possible to determine a T/D index for each inducer and it is proposed that this index is useful in assessing the potential toxicity of microsomal enzyme inducers.


[Effects of aflatoxins B1 on glucose-6-phosphatase activity in kidney and liver of rats (Rattus rattus norvegicus)]. The authors observed the influence of the B1 aflatoxin over rat liver and kidneys glucose-6-phosphatase activity. Animals aged 30 and 60 days received B1 aflatoxin in oil, 1 mcg/g and 5 mcg/g of body weight. The parameters were observed 6, 24 and 48 hours after the micotoxin administration. There was significant decrease of glucemia in the 30 days animals. In the 60 days animals the results suggested possible increase in the liver glucose-6-phosphatase and marked decrease in glycogen.


The airborne dispersal of foot-and-mouth disease virus from vaccinated and recovered pigs, cattle and sheep after exposure to infection. Foot-and-mouth disease virus was detected during two periods in the air of looseboxes which housed susceptible, vaccinated or recovered pigs, cattle or sheep exposed to infection. The first was 30 min to 22 h after exposure and occurred in all animals. The second was two to seven days after exposure and occurred with those susceptible and vaccinated animals which developed clinical lesions, and with vaccinated and recovered pigs and sheep, which did not develop clinical lesions. Vaccination of animals before exposure resulted in less or no virus being detected. The virus during the first period was attributed to virus trapped on the animal during exposure, and the virus during the second period to limited multiplication in the respiratory tract. Control of movement for two weeks after contact with infection is suggested as a means of preventing spread of foot-and-mouth disease in areas that contain vaccinated animals.


[Lipids and beta-lipoproteins in hepatic cirrhosis]. The authors carried out a study of serum lipids and beta-lipoproteins using chemical methods commonly available in clinical pathological laboratories. The study was based on 72 men and women who were chemically and clinically healthy and 41 other patients with  biopsy confirmed hepatic cirrhosis, clinically decompensated. In cirrhotic patients there is a decrease in lipid and beta-lipoprotein values in serum. In plasma cirrhotics show a decrease in beta-lipoproteins. In addition the beta-lipoprotien molecule has a different make-up in cirrhotics which statistically is significantly altered from that seen in healthy patients. The graphic correlation between cholesterol, phospholipids and esterified fatty acids in serum as well as in beta-lipoproteins shows a different theoretical equation in the healty and cirrhotic patient. The beta-lipoproteins in cirrhotics are less atherogenic than the corresponding molecules in healthy individuals. The results here presented suggest that there is an important quantitative and qualitative alternation in lipid metabolism and in the biosynthesis of plasma lipoproteins in the uncontrolled cirrhotic.


[Primary maxillary location of myoblastoma]. The authors report the case of a myoblastoma with multiple successive and rare localisations: maxilla, cheek, lymphatics, lungs, liver and hyoid bone, with a fatal course over 28 months. They recall the possible malignancy of this tumour even in the absence of histological criteria and suggest its classification on bases which at present are only clinical.


Undernutrition and immunity: smallpox vaccination in chronically starved, undernourished subjects and its immunologic evaluation. This study illustrates the specific immune response of chronically starved, undernourished adults after inoculation of live smallpox vaccine. It produced no adverse effect, and major vaccinial reaction was observed in all. 63% of undernourished individuals showed a fourfold or greater rise of the neutralizing antibody titre. In contrast, only 9% of normal healthy subjects could show similar response. However, the prevaccination titre was much lower in the undernourished group than in the control group, and the postvaccination titre also remained persistently lower in the former than in the latter group. Furthermore, whereas the specific humoral antibody response in the undernourished subjects was partially adequate, the development of specific cellular immunity against vaccinia was remarkably poor, indicating that smallpox vaccination in these subjects might be less effective against variola infection. This observed profound effect of chronic starvation and severe undernutrition on the immune apparatus was possibly multifactorial, protein depletion being the most important factor, as proved by the significantly low serum albumin level. The significantly low peripheral blood lymphocyte count and spectacular unresponsiveness to many antigens in these individuals suggested profound depression of the thymolymphatic system. Further, the significantly low level of neutralizing antibody in the malnourished subjects suggested that the formation of this protective antibody might necessitate the cooperation of T lymphocytes.


Human skeletal muscle in bacterial infection: enzyme activities and their relationship to age. 8 male patients (age 65-82 years) suffering from bacterial pneumonia or erysipelas were subjected to skeletal muscle biopsies. Significantly lower activities of lactate dehydrogenase (LDH) and glyceraldehyde-3-phosphate dehydrogenase (TPD) of skeletal muscle were recorded in the acute phase of the illness as compared to after the end of the convalescent phase. For citrate synthetase (CS) a similar although non-significant tendency was observed, while cytochrome c oxidase (CYTOX) was not altered by infection. Similar results have been reported in young patients with viral and mycoplasma infections. In the old patients the activity of LDH was approximately half of that found in the young patients (and in young controls confined to bed) on all occasions of measurement.


[Rheumatic manifestations of Gougerot-Houwers-Sjögren syndrome]. The authors retrospectively survey the concept of the Gougerot-Houwers-5jögren syndrome which links articular disease with the "dry" syndrome (pharyngitis sicca) and then go on to study the rheumatic conditions found in the Gougerot-Houwers-Sjögren syndrome. They point out that the association between the "dry" syndrome and rheumatic appearances varies in frequency according as whether the problem is seen from a rheumatological, dermatological, ophthalmological or stomatological point of view. They establish the frequency of the various rheumatic conditions, stressing the importance of the association with rheumatoid polyarthritis. They study the associated biological and visceral backgrounds, the thyroid, renal, digestive, blood, neural, allergic and immunological conditions and describe the rheumatic appearances of the other collagenoses associated with the "dry" syndrome. They conclude with the current difficulty of restricting the scope of the Gougerot-Houwers-Sjögren syndrome when histological and scintigraphic techniques have broadened it. They would like to see exact criteria adopted to define this syndrome.


Haemophilus parainfluenzae infection of the central nervous system. A report on two infants. Two cases of infection of the central nervous system (CNS) with Haemophilus parainfluenzae--a 12-month-old girl with meningitis and a 17-month-old girl with brain abscess--are reported. Both infants had long-standing upper respiratory infection before CNS disease. Both recovered after treatment.


Neuropathy and the automatic analysis of electromyographic signals from vibration exposed workers. An automatic analysis of the electromyographic activity of the extensor digitorum communis, first dorsal interosseus and opponens pollicis muscles was performed, and both motor and sensory conduction velocities of the median and ulnar nerves were measured in the study of neuropathic changes that occur in traumatic vasospastic disease. Twenty-eight forest workers and 10 pneumatic-tool operators, all with a long occupational exposure to local vibration of the hands, were studied with these neurophysiological methods and general clinical and roentgenological examinations. Twenty male manual workers with a similar age distribution served as the comparison group. The most sensitive measures which separated the subjects with traumatic vasospastic disease from the nonexposed workers were the conduction velocity of the slower motor fibers of the ulnar nerve, the distal sensory conduction velocity and the motor distal latency of the median nerve. The duration and rise time of the averaged muscular potentials of intrinsic hand muscles correlated especially with those nerve conduction velocities which were the most sensitive in exhibiting neuropathic changes.


Hypertension: increase of collagen biosynthesis in arteries but not in veins. In two models of hypertension in rats, it was shown that collagen synthesis and deposition are increased in arteries where blood pressure is elevated. By contrast, there were no alterations in any of the markers of collagen synthesis in veins, where blood pressure was only slightly elevated. It would appear that the stimulus for vascular collagen synthesis is provided by a direct effect of the increased pressure on the arterial cells rather than by a humoral factor released into the general circulation.


Establishment of a cell line with associated Epstein-Barr-like virus from a leukemic orangutan. An Epstein-Barr virus like herpesvirus has been isolated from a lymphoid cell line derived from an orangutan with spontaneous myelomonocytic leukemia. Herpesvirus has not previously been isolated from this species of higher ape.


Adrenergic stimulation of taurine transport by the heart. A high-affinity transport system that is specific for beta-amino acids has been delineated in rat hearts. This system transports the cardiotonic sulfonic amino acid taurine. beta-Adrenergic stimulation increases the transport capacity without effect on alpha-amino acid uptake, as does stimulation with adenosine 3',5'-monophosphate or theophylline. The existence of such an uptake system for taurine in the heart accounts for the high intra- to extracellular concentration gradient that is maintained, and suggests that cardiac stress is associated with increased taurine uptake. This may explain why taurine is the only amino acid to be markedly elevated in congestive heart failure. Taurine is a modifier of calcium fluxes in the heart, as are beta-adrenergic agonists. The presence of this uptake system suggests a link between beta-adrenergic stimulation of calcium and taurine fluxes.


[Hypercalcemia during acute intermittent porphyria. Apropos of 3 cases]. 3 cases of hypercalcemia are reported, among 14 tetraplegic patients with porphyria. The calciuria, the estimations of parathormone, calcitonin and the isotopic calcium balance studies, suggested in the two most serious cases, hypercalcemia due to immobilisation. The main factor seems to be the duration of the immobilisation. The predisposing role of renal failure and catecholamines is discussed.


[Severe hypercalcemia during hyperthyroidism]. A particularly high hypercalcemia (141 mg/ml) was observed in a man with Graves' disease. An intense muscle asthenia, with lack of dynamism and vomiting which may cause dehydration, are the most suggestive signs of hypercalcemia. Bone biopsy and above all parathormone estimations permit one to eliminate associated hyperparathyroidism. The efficacy of mithramycin used alone, without any other hypocalcemic drug, was remarkable. The direct responsibility of thyrotoxicosis as a cause of the calcium disorder seems undoubted but the precise mechanism of the hypercalcemia remains unexplained.


[Complication caused by abuse of alkalies in the treatment of ulcers]. The authors report the case of a 57 year old man who had taken for several years large quantities of alkaline drugs to relieve pain due to a gastric ulcer. This man presented acute digestive symptoms, and a confusional syndrome explained by various metabolic disturbance and especially hypercalcemia at 145 mg. Stopping the alkalis permitted within a few days the disappearance of the clinical symptoms and the correction of the laboratory disturbances. In the light of this case, the authors study the main clinical cases which have been described either in their acute form or in their chronic form (Burnett's syndrome). They discuss above all the physiopathology of these manifestations and it seems to them that the hypercalcemia is more important than the alkalosis. It remains to be explained why only a small number of subjects are exposed to these metabolic complications. There seems to be an individual hypersensitivity for under normal conditions, excess calcium is not sufficient to induce hypercalcemia.


[Essential hypernatremia with hypovolemia caused by hypodipsia and partial diabetes insipidus]. The authors report the case of 13 year old girl presenting with chronic hypernatremia. This case should be considered as either neurogenic or essential hypernatremia. Partial diabetes insipidus and hypodipsia hypernatremia. Partial diabetes insipidus and hypodipsia are the cause of chronic hypovolemia and a new homeostasis with an exceptionally high level of sodium (isoosmotic point 154 mEq/l). No cause was found and in particular, the search for a cerebral disease was until now proved negative.


[Hyponatremia and myxedamatous coma].

[Hyponatremia and myxedamatous coma]. The authors report a case of coma due to peripheral myxoedema with severe hyponatremia (111 mq) and low urinary sodium. The clinical and metabolic disorders regressed within ten days under treatment with thyroid. The frequency of hyponatremia during myxoedema coma is recalled and the pathogenic mechanism discussed. Although the adrenal origin seems excluded, there is possibly some hypervasopresinism, but it seems finally that the thyroxin-dependent hyponatremia is of renal origin.


[Syndrome of inappropriate secretion of vasopressin. Apropos of 3 cases]. 3 cases of inappropriate vasopressin secretion during one case of anaplastic carcinoma of the lung, one case of carcinoma of the prostate with bony metastases and one case of acute intermittent porphyria are presented. The plasma levels of vasopressin, measured by radioimmunoassay were high. Treatment with demeclocycline was attempted in one case. The clearance of free water was positive but the treatment was poorly tolerated by the digestive tract.


[Striatal syndrome and hypokalemia].

[Striatal syndrome and hypokalemia]. The authors present the case of a patient with a striated syndrome resembling Wilson's disease but without the disorder of cooper metabolism. The clinical picture was completely masked by a hypokalemia at 1 mEq/l following urinary loss of this cation, due to ascending interstitial nephritis. Correction of the potassium deficiency produced rapid reappearance of the initial neurological syndrome.


[Hypokalemic familial periodic paralysis with basal electrocardiographic changes]. The authors report the case of an 18 year old girl with nocturnal tetraplegia. There was a family history of Westphal periodic paralysis, and a past history of transient paralysis two years previously. The serum potassium was 2.3 mEq/l. The patient was cured by intravenous drip of potassium chloride. There was a reactionary hyperinsulinism. The red cell potassium was lowered. There was a fall in the exchangeable and total potassium pool. The E.C.G. changes; observed during the acute attack of paralysis, persisted afterwards, which is unusual.


[Paralysis with hypokalemia by transfer, treated by acetazolamide]. A case of familial paralysis with hypokalemia is presented. Acetazolamide at a dose of 500 mg daily prevents the onset of acute attacks. Under acetazolamide, an oral glucose tolerance test is not followed by hypokalemia. The association of glucose and insulin is unable to trigger off a paralytic attack although without acetazolamide, the same protocol had 5 months previously precipitated tetraplegia with hypokalemia. These results are compared with those in the literature.


[Hypokalemia and hypomagnesemia in a cirrhotic patient. Correction of metabolic disorders by magnesium]. The authors report the case of a cirrhotic with severe hypokalemia (2 mEq/l) responding incompletely to attempts at correction by classical treatments. The findings of a serum and red cell magnesium deficiency led to administration of this electrolyte which proved efficacous. They then recall the mechanism of hypokalemia and hypomagnesemia in alcoholics, study the possible relationship between these abnormalities, their noxious effects and suggest a treatment.


[Bismuth treatment and blood bismuth levels]. The authors report the results of bismuth blood levels in 41 patients treated by oral route with bismuth salts used in gastro-enterology according to the Bensaude rule (10 to 20 g/day, 20 days/month). Median bismuth blood level during the period of treatment amounts to 13 microgram/l. It decreases to 7 microgram/l during the period of therapeutic withdrawal. In patients with bismuth encephalopathies (63 cases recorded in the literature) median values range from 680 to 700 microgram/l. The authors recommend the determination of bismuth blood levels as a monitoring method in bismuth treatment and propose the following values:--normal level during treatment : less than 50 microgram/l (in Bi metal);--alarm level : 50 to 100 microgram/l : (patients to be monitored);--toxicity level less than 100 microgram/l : (treatment to be interrupted).


[Deceptive and revealing clinical forms of acute respiratory insufficience in chronic bronchopneumopathies]. The authors report 6 cases of acute respiratory failure complicating chronic bronchial and lung disease admitted to hospital with the diagnosis of: heart disease, 3 cases, pulmonary oedema, pulmonary embolism, atrial flutter; status asthmaticus : one case; neuro-psychiatric disease : 2 cases (toxic coma and agitation). The authors emphasize the frequency of chronic bronchial disease and recall the signs of acute decompensation discussing the possible difficulties in diagnosis and the therapeutic implications.


[Misleading pulmonary emboliu].

[Misleading pulmonary emboliu]. The authors report 12 cases of pulmonary embolism with misleading signs and discuss the difficulty in diagnosis: 1) the frequency of incomplete forms; 2) lack of specificity of the clinical and paraclinical picture of pulmonary embolism which may simulate pulmonary or heart disease; 3) difficulties in interpretation of the signs of pulmonary embolism in cases of prior heart or pulmonary disease.


[Myotonic dystrophy and acute respiratory insufficiency]. Myotonic dystrophy or Steinert's disease may be discovered during acute respiratory failure, sometimes caused by a general anaesthetic. It complicates chronic respiratory failure which is present in almost all cases, both restrictive and obstructive, the clinical signs of which progress with the myopathy. Apart from myotonic degeneration of the respiratory muscles, a hypoventilation syndrome of central origin has been described, but the etiology of this respiratory failure is dominated by repeated aspiration pneumonia favoured by constant dysphagia and passage of food into the trachea and poor cough reflex. One should attempt to correct this.


[HLA system and rhizomelic pseudopolyarthritis]. 26 HLA antigens of the loci A and B were studied in 50 patients with pseudo-polyarthritis and in 300 control subjects without any joint disease. The arthritis was isolated and not associated with temporal arteritis. An increase in frequency of both HLA antigens was noted in the patients studied: HLA-B5 = 24% as against 13% in controls (P = 0.05 and Pc NS). HLA-Bw38 = 18% as against 5.33% in controls (p = 0.002 - Pc = o.05). The rise in frequency of HLA-B5 and HLA-Bw38 was also found in 19 subjects with polyarthritis and temporal arteritis but not in 31 patients with temporal arteritis alone. In this disease, a link with the HLA-B14 antigen was noted in 50 cases (22.9% as against 8.6% in control). These results suggest that arthritis and temporal arteritis although sometimes associated are probably distinct diseases.


[Hematological and clinical manifestations of bone marrow metastasis of carcinomas. Apropos of 36 cases verified by biopsy]. A retrospective study of 36 cases of bone marrow metastases from carcinoma is reported. In all cases, the presence of tumour cells was confirmed by needle biopsy of the bone marrow. The clinical picture was fairly typical: decline in general health, fever, bony pain and skin and mucosal hemorrhages. Radiological lesions of the skeleton were present in 64% of cases. Sometimes the blood disorders were isolated. Anemia was almost constant (86), normochromic, normocytic, and may be associated with leukocytosis and thrombopenia. Pancytopenia is rarer as also is a rise in the number of platelets. Erythremia, very suggestive, is demonstrated in 73% of the blood smears. In 31% of the slides examined again, schizocytes were found among the normal red cells. Disorders of hemostasis were easily circumscribed. As fibrinolysis was sometime found, hemostasis was studied as a routine in all patients. The special recruitment of a hematology unit explains the high frequency of blood abnormalities in this series of bone metastases.


[Parenteral feeding. Prevention of complications in adults during exclusive mid-term parenteral feeding]. The benefits of parenteral feeding need no longer be emphasised. However, qualitative and quantitative food supplements raise a certain number of difficulties which should be better known. Infection is the most frequent complication. It may be avoided by strict aseptic precautions throughout parenteral feeding. Hypoglycemia is a major risk owing to the possible consequence. Hyperglycemia and its consequence of osmotic polyuria is more frequent and should be controlled to avoid loss of water and salt. Complications due to the use of lipid emulsions are exceptional when soya oil is used. Hypophosphoremia should be corrected by increasing phosphate intake. Hypocalcemia is common; it is often associated with hypoproteinemia and sometime a low calcium intake, vitamin D deficiency or a sudden increase in phosphate intake. Vitamin deficiencies, hypomagnesemia, and oligo-element deficiencies should be correcty by appropriate supplements.


The lipid disorders centre at the Transvaal Memorial Hospital for Children. A review of the first 30 months. A specialized clinic for the investigation and treatment of familial lipoprotein disorders was started at the Transvaal Memorial Hospital for Children in July 1972. The reasons for its formation, its siting at a paediatric hospital and patient protocols are detailed. During the first 30 months, 195 patients with familial hyperlipoproteinaemia were seen. The ethnic distribution revealed a disproportionately high prevalence of lipoprotein disorders in the Afrikaner population. The most common lipoprotein disturbance seen was familial hypercholesterolaemia or Fredrickson type II hyperlipoproteinaemia, which was found in 84% of the patients. Included in this group were 18 homozygotes. The majority of patients were between 1 and 20 years, while few were over the age of 50. The incidence of ischaemic heart disease at various ages in the clinic population is reported. Results of therapy, both dietary and drug, for the various types of hyperlipoproteinaemia are presented. The contribution of familial hypercholesterolaemia to the high incidence of ischaemic heart disease and its possible implications in young White South Africans is discussed.


Comparison of lactate and pyruvate during endotoxic shock. The livers of Sprague-Dawley rats, previously injected with endotoxin, were isolated and perfused in a controlled environment with known amounts of lactate or pyruvate. Samples were taken after one hour to determine substrate utilization, content of oxidized and reduced metabolites, adenylate energy charge and reduced nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide + ratio. In this experiment, it was found that, in the group treated with endotoxin and perfused with lactate substrate, utilization and adenylate energy charge were reduced, while the concentration of reduced metabolites and reduced nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide + ratio were increased. We conclude that infusion of lactate solutions to patients in a state of shock may have an adverse effect upon cellular function.


Postresection stage grouping in carcinoma of the lung. The postsurgical treatment classification and staging system for carcinoma of the lung has been evaluated in a series of 403 patients admitted to a completed prospective randomized adjuvant cancer chemotherapy trial conducted by the Veterans Administration Surgical Adjuvant Group. The proposed T, N and M classification suggested by the American Joint Committee for Cancer Staging and End Results Reporting is supported. However, the stage groupings as suggested by the Committee fails to separate adequately the various prognostic groups. This appears to be better accomplished by the stage grouping modification suggested by the Radiation Therapy Oncology Group. In the latter schema, the five year survival rate of patients with postsurgical treatment Stage I disease is 40.9 per cent; Stage II, 26.2 per cent, and Stage III, 10.5 per cent. In the Joint Committee classification, these survival rates are 30.8 per cent, 25.5 per cent and 10.5 per cent, respectively. In addition, 18 patients with undifferentiated small cell carcinoma were also evaluated. The long term survival of three of sixe patients with small peripheral lesions without metastatic lymph node involvement supports the opinion that resection of these specific lesions continues to be the treatment of choice.


The transfer of estrone glucuronide to bile in an isolated perfused rat liver system. An isolated rat liver perfusion system has been utilized in a study of the biliary excretion of estrone glucuronide. The estrogen was initially shown to be excreted without prior metabolism. Disappearance from the medium was rapid and biliary concentrations exceeded that in the medium by more than a thousand-fold. Disappearance rates were decreased when medium estrone glucuronide concentrations exceeded 0.29 mM. Inhibition by other steroidal conjugates, testosterone glucuronide, 2-methoxyestrone (3-hydroxy-2-methoxy-estra-1,3,5(10)-trien-17-one glucuronide and 2-hydroxyestrone (2,3-dihydroxyestra-1,3,5(10)-trien-17-one) glutathione, was also demonstrated. Phenolphthalein glucuronide, at 10 times the molar concentration of estrone glucuronide, did not affect the medium clearance of the latter compound. These findings indicate the possibility of utilizing this system for further studies of possible interactions by other organic compounds for excretion via the biliary route.


Primary carcinoma of the liver in Malawi: a review of 24 cases. A consecutive series of 24 cases of primary carcinoma of the liver in Malawi has been investigated. Histologically, all were hepatocellular carcinomas (HCC). All patients were African Bantus, the average age was 42.7, and the sex ratio was men 3.5:women 1. The duration of symptoms attributable to HCC was about 5 months previous to admission to hospital and was in no case preceded by clinically manifest cirrhosis. The clinical picture was rather uniform with pain in the region of the liver, emaciation and nodular hepatomegaly as the most important features. One of the patients had repeated attacks of hypoglycaemic coma. Sera from 11 out of 13 patients contained alpha-feto-protein. Hepatitis-associated antigen and antibody in the serum were found in 7 and 6 out of 16 and 14 cases respectively. Serum B12 and serum unsaturated B12 binding capacity were moderately raised in most patients. The prognosis was poor, the average time of survival was 4.8 weeks after admission. The cause of death was most frequently hepatic coma. HCC in the African Bantu shows some different features from the same disease in the Western Hemisphere: The incidence is much higher; the patients are younger. The neoplasm commonly develops in a clinically latent cirrhosis. The latter is not caused by alcohol, but is presumably a sequel of hepatitis. It is possible that aflatoxin is the carcinogenic factor, acting more readily in a cirrhotic than in a normal liver.


Ultrastructural localization of diaminobenzidine reactivity in leishmania donovani promastigotes. The ultrastructural localization of the activities of two enzyme systems in the culture forms of Leishmania donovani was shown by means of the diaminobenzidine techniques. The consistent deposition of electron dense reaction product of DAB oxidation without H2O2 in the kinetoplast and mitochondrial cristae and membranes was taken as evidence of the presence of cytochrome oxidase activity and cytochrome c. In the presence of H2O2, a more intense DAB oxidation was attributed to the activity of a peroxidase, possibly cytochrome c peroxidase. Mitochondrial and kinetoplast reactions to DAB were completely inhibited by KCN, methanol-nitroprusside, and by heating to 50 degrees C for 10 min. On the other hand, no inhibitory effect was observed with 100 mM 3-amino-1,2,4-triazole. Under all conditions of incubation tested, the microbodies were completely unreactive to DAB staining, which was utilized as the basis for their identification. These organelles are rounded, moderately electron-opaque bodies with a finely granular matrix and fine tubules or cores and are limited by a single membrane. Under normal staining method, the microbodies were indistinguishable from the rounded sections of mitochondria.


Interaction of ultrasound with neoplastic tissue. III. Electron microscopic demonstration of ulstrasonic destruction of Wilms tumor and its cellular membranes. Exposure of 300 adult, male Wistar-Furth rats bearing subcutaneous implants of Wilms tumor to a vertically oriented planar ultrasound beam consistently resulted in a marked decrease in the growth rates of the tumors with an increase in the survival times of the treated animals. Grossly, the local effects consisted of a flattening of the tumors with clean excavation of their bases. Histologically, a line of demarcation was demonstrated between the sonicated (or destroyed) and non-sonicated portions of the same rat Wilms tumors. The sonicated portions exhibited a complete loss of the normal spatial relationship between the tumor epithelium and its surrounding mesenchyme. Ghost residuals of portions of individual cytoplasmic cell borders and nuclei with condensed chromatin patterns still could be discerned. Electron microscopy demonstrated a marked destruction of the nuclear and cytoplasmic cellular membranes with a migration of destroyed condensed chromatin material into the surrounding cytoplasm.


Investigations of urinary stone formation following persorption. Persorption is the excretion in urine of particles that have been absorbed (persorbed) from the gastrointestinal tract. In experiments with rats the effect of Herbst was combined with the production of renal calcium oxalate sediments by the oral administration of ethylene glycol and acidification with ammonium chloride. We used this method to investigate whether persorbed corpuscula may represent nuclei of crystallization in the formation of renal calculi. Lead sulfide, zirconium silicate and 45Ca-labeled calcium oxalate crystals were used as persorbable model bodies. It became apparent that orally supplied lead sulfide and zirconium silicate crystals could be found in the urine and the kidneys but they did not function as crystallization centers in the calcium oxalate sediments. However, radioactive labeled calcium could be demonstrated histoautoradiographically within the renal concrements. Our experiments showed that persorbed calcium oxalate crystals can work as nuclei for stone formation.


Simplified assessment of pituitary-adrenal axis in a stable group of chronic hemodialysis patients. 1) A stable group of hemodialysis patients in our study do not have a normal response to the cosyntropin test; 2) although one would expect chronic renal failure patients to accommodate to hemodialysis, our study demonstrates that hemodialysis may still serve as a useful stress test; 3) the reduced response to the metyrapone suppression test in our stable group of hemodialysis patients suggests impairment of the feedback mechanism of the pituitary-adrenal axis.


[Banded filamentous associates in the intra- and extracellular space in connection with collagen degradation (author's transl)]. Banded fibrous associates are described in the extracellular space of connective tissue from human endometrium, Ehlers-Danlos syndrome and of tendon rupture. In the cases of morbus Dupuytren these associates are also found as intracellular inclusions. The banded structures are interpreted as states of an enzymatically induced degradation of collagen in correlation with Type-III collagen.


Storage of proteins in the rough endoplasmic reticulum of human hepatocytes in a patient with normal blood proteins, on oral contraceptives. Aspects of protein storage in the rough endoplasmic reticulum of hepatocytes, comparable with those reported in alpha1-antitrypsine (AAT) deficiency, have been observed in the course of jaundice in a woman presenting no evident abnormality in AAT or other blood proteins. In light microscopy, most hepatocytes contained characteristic globular inclusions but they were PAS negative and did not react with anti-AAT antibodies. This storage of protein ceased at the time the jaundice disappeared. Prolonged treatment with high doses of contraceptive steroids may have been involved in this peculiar reaction of the hepatocytes.


[Cytological diagnosis of salivary gland tumors]. The rationale of using clinical cytodiagnostics for preoperative recognition of salivary gland neoplasms is shown. As a result of using diagnostic puncturing in 44 examined patients the character of the pathological process was precisely determined in 88.6%, and the tumor was typed histologically in 66.7%.


[RNA biosynthesis in the ascitic cells of Ehrlich's carcinoma and Zajdela's hepatoma under conditions of blocked oxidative phosphorylation]. In experiments in vitro on ascites tumor cells of Ehrlich carcinoma and Zajdela hepatoma the author studied the effect of 2,4-dinitrophenol (an agent dissociating respiration from phosphorylation) on respiration, glycolysis, resynthesis of ATP and synthesis of basic fractions of cytoplasmic RNA by the incorporation of labeled 3N-uridine precursor. It was shown that under optimum conditions of tumor cell incubation (phosphate-rich Igle medium) in the presence of 6.10(-4) M DNP a sharp activation of anaerobic glycosis is observed as well as increased O2 absorption and high level of ATP. Blocked phosphorylation associated with respiration renders no appreciable effect on the biosynthesis of basic fractions (4 S, 18 S, 28 S) of cytoplasmic RNA.


[Serum lipids in uterine cancer].

[Serum lipids in uterine cancer]. In 40 patients with uterine cancer changes were studied in total lipids, beta-lipoproteids and cholesterol in serum prior to, during and 4 years following the treatment. All patients were characterized by a low level of total lipids and increased cholesterol values, the former were normalized under the influence of the therapy in disappearance of the symptoms. The level of beta-lipoproteids decreased prior to the treatment was reliably increased during it only in patients with cervical cancer subjected to the combination treatment (surgery & irradiation).


[Transforming action of the total RNA preparations isolated from Rous virus-induced sarcomas]. The authors compared the effect of RNA substances isolated from chick sarcomas producing Rous virus and hamster sarcomas not producing the virus. In both species of animals the tumors were induced by the same Rous virus strain (Carr-Zilber). The treatment of embryonal cells cultures both of the chick and hamster with RNA preparations resulted in the morphological transformation. The action of RNA-s would reduce considerably or eliminated totally the effect, while DNA-s failed to influence the activity of the preparations under study. Embryonal cells culture in hamsters proved to be more sensitive to RNA action than chick cells.


[Kinetic study of the effectiveness of chemotherapy of experimental metastases (using a computer)]. Under study was the influence of active antitumor substances on experimental metastasizing tumors. The method for assessment of their efficacy, using an electronic computer, is suggested. Significant differences in the action of the substances on primary tumors and their metastases are shown.


[Study of viremia in chronic human herpetic infection]. Attempts at virus isolation were made on the blood specimens from patients with relapsing herpesvirus infection. Examinations of over 100 blood specimens from patients with various localizations of herpetic lesions yielded II strains of herpesvirus. In all the cases the virus was isolated from a mixture of leukocytes with erythrocytes of the blood of patients. The method of cocultivation of blood leukocytes with cell cultures was most sensitive and yielded 7 herpesvirus isolates. The herpesvirus isolates vary in their biological and antigenic properties.


[Transfection by integrated proviruses]. Three lines of continuous mouse L cells were compared: one of them contained only its endogenic oncornavirus, another was contaminated with SV5 virus, and a third was obtained from the second line chronically infected with vesicular stomatitis virus. Experiments with transfection showed that it was possible to recover SV5 virus from the two former cultures and vesicular stomatitis virus from the latter.


[Study of the antigenic properties of herpesvirus strains isolated from herpetic lesions at different sites]. The antigenic properties of 15 strains of hepesvirus isolated from herpetic lesions of different localization were studied. The serotype of each strain was established by the neutralization tests with hyperimmune sera to the reference type 1 and 2 strains: the cross-neutralization tests revealed antigenic relationships between the strains of 1 and 2 serotypes. Most strains isolated from lesions of the genitalia belonged to type 2, although one strain isolated in herpes genitalis belonged to type 1, and 2 strains isolated from facial lesions also belonged to type 2. These results confirm the necessity of using inactivated polyvaccine prepared from herpesvirus strains of antigenic types 1 and 2 for relapse control therapy instead of using monovalent type 1 and type 2 vaccines as reported by foreign authors.


[Study of the morphological aspects of Okhotskiĭ virus replication in a chick fibroblast culture]. Electron microscopic studies of chick embryo fibroblast cells 24 hours after infection with Okhotsky virus revealed changes typical orbivirus infection in the cytoplasm and the nuclei of the cells. The nuclei of the infected cells contained fine-granular matrices with forming virus particles and tubular structures. The cell cytoplasm also contained tubular structures, crystal arrays, fine-granular matrices and virus particles 50-60 nm in diameter.


[Herpetic infection of the oral cavity in guinea pigs]. A convenient experimental model for serial studies of herpes simplex of the buccal mucosa has been developed in guinea pigs by application of fresh isolates of herpes simplex virus type 1 from a patient with primary herpetic gingivo-stomatitis on prescarified buccal mucosa. The herpetic nature of the eruptions in the oral cavity was confirmed by virus isolations and serologically. The possibility of exogenous reinfection of the buccal mucosa in convalescent animals against the background of humoral virus-neutralizing antibody has been demonstrated. No virus was isolated from the blood, brain, regional lymph nodes, oesophagus, trachea, lungs or liver of the animals with primary herpes simplex of the buccal mucosa. The model is recommended for experimental investigations of herpetic infections of the buccal mucosa.


[Immunofluorescent method of studying autopsy material in acute pneumonia]. The immunofluorescent procedure in examinations of the autopsy material from 304 fatal cases hospitalized for acute pneumonia permitted to diagnose influenza A2 in 29.0%, influenza B in 18.1%, parainfluenza in 3.5%, adenovirus infection in 9.2% and respiratory syncytial virus infection in 3.5% of the cases. In the period of a high incidence of acute respiratory infection, influenza A2 was detected by this method in 40.9% and influenza B in 50% of the cases. Simultaneous examinations of the material in the influenza epidemic period by virological and immunofluorescent methods (63 cases) in 13 cases positive results were obtained with both methods, in 6 cases where influenza viruses were detected the immunofluorescent test was negative, and in 28 cases the positive diagnosis by the immunofluorescent test could not be confirmed virologically. Among the cases examined, 33 were found by the immunofluorescence test to have a mixed respiratory infection, including influenza A2 with other forms of respiratory infection in 18, and influenza B with other respiratory infections in 19 cases. Serological examinations by the complement fixation and hemagglutination inhibition tests on the blood from fatal cases irrespective of the time of examination, as a rule, revealed antibody in low titres which did not confirm the diagnosis.


[Quantitative indices and physico-chemical properties of non-specific inhibitors of influenza A virus hemagglutination in the sera of different species of animals and birds]. The results of studies of the quantitative values of nonspecific antihemagglutinins of influenza viruses in the sera of birds, laboratory, wild and domestic animals (altogether 27 species) are presented. The antiviral inhibitors characterized by a number of physicochemical properties (sensitivity to heating, KIO4, trypsin, rivanol, 2-mercaptoethanol) were divided into 3 groups, sera of sheep, goats and cattle making up a separate group with regard to their sensitivity to heating and treatment with KIO4. Studies using molecular screen chromatography demonstrated the nonspecific inhibitors present in bovine sera to be heterogenous both in type (thermolabile and thermostable) and in the molecular composition. Alongside with thermolabile inhibitors of macroglobulin nature, thermostabe 19S and 4S inhibitors were identified.


[Interaction of Sindbis virus with a culture of cells producing oncornavirus]. Electron microscopy and biophysical methods were used for examinations of primarily trypsinized chick fibroblast cell culture spontaneously producing C-type oncornavirus at 1, 6, and 24 hours after inoculation with Sindbis virus. During the first 6 hours rapid maturation and release of oncornavirus from cells were observed. At later intervals oncornavirus production was inhibited. It is assumed that in the system under study, biosynthesis of oncornavirus and Sindbis virus occur separately.


[Sensitivity of Japanese quail, embryos and embryonal tissue culture to infection with several avian viruses]. The sensitivity of the biological system Japanese quail-embryo-quail fibroblast cultures to some common fowl viruses (Newcastle disease virus, infectious laryngotracheitis and infectious bronchitis viruses) was studied. Japanese quails, their embryos and embryo cell cultures were found to be sensitive to Newcastle disease virus infection. The virus reproduction was accompanied by death of embryos and destruction of cell culture. Japanese quails are sensitive to infectious laryngotracheitis virus given as aerosol. Reproduction of this virus in embryos was accompanied by formation of plaques on the chorioallantoic membrane and in the cell cultures by incomplete cytopathic effect. Japanese quails were found to be sensitive to infectious bronchitis virus, while their embryos and embryo cell cultures had low susceptibility to this virus.


[Mechanism of postvaccinal immunity in Marek's disease]. The apathogenic variant No. 38 of Marek's disease virus, Kekava strain (MDV-Kekava), at the level of the 16th and 45th passages in vitro made chickens resistant to Marek's disease when inoculated 14 days before the infection of the chickens with the pathogenic variant No. 55 of MDV-Kekava. A simultaneous administration of both variants did not protect the animals against the disease. The occurrence in variants of MDV-Kekava of genetic markets manifest upon virus passages in chick embryo fibroblast (CEF) cultures provided an opportunity to study the interactions between them in chickens, using the CEF culture for virus isolation. The results of virus isolation from the blood cells of vaccinated chickens showed interference to occur in chickens between the virus variants as the rate of isolation of the pathogenic variant was 3 times as low as that of apathogenic MDV-Kekava, and both virus variants persisted in different cells. When chickens were inoculated simultaneously with both virus variants, the recovery rate of both pathogenic and apathogenic variants from the blood cells was similar. In such cases, persistence of two virus variants in one cell is also possible. The experimental results suggest that in the mechanism of resistance of vaccinated chickens to Marek's disease a significant role may be played by interference between the viruses in which the "occupation" of target cells by vaccine virus protects them from pathogenic MDV.


[Differences in the antiviral and antioncogenic action of interferons produced in murine peritoneal cells and in Krebs-2 ascitic carcinoma cells]. Comparisons of native preparation of mouse interferons, "macrophage" and "Krebs" revealed some differences, Thus, the minimal time necessary for the development of resistance to vesicular stomatitis virus (VSV) in L cells treated with "macrophage" and "Krebs" interferon was 5 and 2 hours, respectively. The activity of the lysosomal enzyme of acid phosphatase was considerably higher in the cells treated with "Krebs" interferon and infected with VSV than with "macrophage" interferon. Differences in the antiviral and antioncogenic properties of fractions No. 1 and No. 5 of these interferons obtained in fractionation of native interferon preparations by the cryomethod were demonstrated. In particular, fraction No. 5 of "Krebs" interferon, in contrast to that of "macrophage" interferon, had no antioncogenic properties but did have antiviral properties. It is suggested that these differences are due to the presence in native preparations of different substances capable of exerting an effect on interferon.


Survival in lung cancer.

Survival in lung cancer. Analysis was carried out according to stage and tissue type of 392 consecutive cases of lung cancer diagnosed at David Grant Medical Center between 1960 and 1974. Biphasic survival curves were described with a variable primary phase and a constant (1.1 percent per month) secondary phase. Survival was found to correlate both to histology and stage. The best survival was found in stage I bronchoalveolar carcinoma. Even in the more favorable categories a leveling off of survival was not found. This study strongly suggests that surgical treatment of lung cancer, while beneficial, cannot expect to be considered as a curative procedure in more than 10 percent of cases. Radiotherapy did not prolong survival.


The biology of the rheumatoid synovial cell. Over the past 15 years, many of the elaborate research techniques of cell biology and biochemistry have been applied toward discovering the cause of rheumatoid arthritis. Consequently, it is valuable to review the morphological, physiological and biochemical alterations that have been observed in rheumatoid synovial cells. All of the changes observed suggest that a viral agent may form the basis for these alterations. However, studies to date have failed to isolate or identify the putative causative virus and the search continues.


[Therapeutic and diagnostic problems in a patient with insulinoma (author's transl)]. Surgical intervention in organic hyperinsulinism is based on prior accurate biochemical assessment. The emergent problems are discussed in a case with hypoglycaemic attacks, where "blind" pancreatic resections had been performed in two occasions without success. Finally, after demonstration of hyperinsulinaemia and localization of the tumour by selective angiography an adenoma was removed surgically. The postoperative complications, including the development of insulin-dependent diabetes, demonstrate the inherent risks of blind distal pancreatectomy for suspected insulinoma.


[Secondary hyperlipoproteinemias].

[Secondary hyperlipoproteinemias]. At first the review deals with significance of the apoproteins for the metabolism of the lipoproteins, especially VLDL. Thus, for instance the apo-C is a cofactor for the lipase of the fatty tissue which hydrolyses the chylomicron-TG. The author enters examples of the secondary hyperlipoproteinaemias: hyperlipoproteinaemias in diseases of the liver and of the kidneys, in pancreatitis and in diabetes. In cholestasis an abnormal lipoprotein called LP-X is observed, in other diseases of the liver the beta2LP corresponding to the VLDL-intermediate. Causes for increases of lipoproteins in renal diseases are probably disturbances of the protein metabolism. There are close correlations between hyperlipoproteinaemias and pancreatitis. In diabetes primary hyperlipoproteinaemias in maturity-onset-diabetes are to be differed from clearly secondary ones in juvenile-onset-diabetes as well as such ones in nephropathy. The therapy of the secondary hyperlipoproteinaemias is shortly discussed.


Phenotypic properties of neoplastic cell lines developed from fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo. We have recently reported that fetal BD IX-rat brain cells (FBC), transferred to long-term culture after a transplacental pulse of EtNU on the 18th day of gestation, undergo neoplastic transformation in vitro ("BT-cell lines"). Tumors developed upon s.c. reimplantation of BT-cells into baby BD IX-rats, appeared histologically as neurinoma-, glioma- or glioblastoma-like, and frequently as pleiomorphic neoplasms. In spite of a more atypic cellular morphology, these tumors grossly resembled the different types of neuroectodermal rat neoplasms induced by EtNU in vivo. Like the neoplastic cell culture lines derived from EtNU-induced, neuroectodermal BD IX-rat tumors ("V-cell lines"), the BT-lines contained multipolar glia-like cells, but also flat cells with fewer and shorter cytoplasmic processes, and occasionally giant cells. Both the V- and BT-lines showed different levels of aneuploidy. They contained multiple subpopulations of cells, as reflected, e.g., by plurimodal pulse-cytophotometric DNA distributions. All lines contained, to varying degrees, the nervous system-specific protein S-100, a "marker" not yet expressed in FBC. There was no indication of more than borderline neurotransmitter activity, suggesting that proliferating (precursor) cells of glial lineages may preferentially undergo malignant transformation after exposure to EtNU during this stage of brain development.


On the function of hormone receptors in the action of steroidal alkylating agents. Steroidal alkylating agents are supposed to bind to steroid hormone receptors in target tissues. By this interaction the steroid portion might act as a carrier for the alkylating group. Three steroidal agents (phenesterin, estradiol mustard, dehydroepiandrosterone mustard) were tested for their capacity to combine with estrogen and androgen receptors in normal and malignant target tissues. For measuring steroid receptor complexes ager gel electrophoresis was used. All three compounds (added at a 10(3)-fold excess) revealed in vitro no competition to receptor sites (estrogen and androgen binding). After preincubation of intact tissue estrogen mustard was effective in inhibiting the binding of 3H-estradiol and dehydroepiandrosterone mustard reduced the uptake of 3H-5alpha-DHT. This may be due to liberating of estradiol and dehydroepiandrosterone, respectively, from the intact molecule. From these data it is unlikely that the cytostatic steroidal agents are more effective than other alkylating drugs.


[Transplacental induction of neurogenic tumors in rabbits (author's transl)]. The oncogenic effect of ethylnitrosourea (ENU) on rabbits during the organogenesis was studied. ENU, dissolved in sodium phosphate (pH 6.0), was injected in a 50 mg/kg dosis intravenously in pregnant dams between the 8th and 10th day of gestation. From 12 offspring 8 grew up normally and appeared unremarkably until 30--36 months of age when neurologic signs first developed. Six rabbits showed one or more tumors along the peripheral nerves. Two rabbits were bearing brain gliomas in the vicinity of the 3rd ventricle. The tumors of the peripheral nervous system (PNS) were of variable size and soft consistency; they had a cut surface of spongy and even cystic appearance. Histologically, the PNS tumors resemble Schwannomas of the Antoni B type. An ultrastructural study of these neoplasms disclosed cells featuring a basal lamina type of lining characteristics of Schwann cells. These findings demonstrate that the exposure of rabbits to ENU during organogenesis results in the induction of neurogenic tumors which become clinically manifest late in life. It seems, therefore, that the selective oncogenic effect of ENU on the nervous tissues of the exposed animals depends exclusively on the stage of organogenesis at which the drug is brought to bear upon the target organ anlage.


Specifically immune mouse T-cells can destroy H-2 compatible murine target cells infected with herpes simplex virus types 1 or 2. Lymphocytes from the spleen (SL) or peritoneal cavities (PL) of HSV-1- or HSV-2-immunized C 3 H mice expressed pronounced cytotoxicity, as measured by 51Cr release assay, against L cells experimentally infected with HSF-types 1 or 2 but not against uninfected L cells. HSV-1 or HSV-2 immune lymphocytes induced substantially more 51Cr release when L-cell targets were infected with homotypic virus compared to those infected with heterotypic virus. Inasmuch as the cytotoxicity of specifically immune C 3 H SL for HSV-infected L cells was selectively eliminated by treatment with AKR anti-theta C 3 H serum plus complement, the effector cells in present system were theta-bearing T cells. Evidence has been provided which indicates that specifically immune T cells express cytotoxicity exclusively directed against different HSV-infected target cells (mouse embryo cells or mouse peritoneal macrophages) which share H-2 antigens with the effector cells.


[The properties of [omega(3-acetylpyridinio)-n-alkyl]adenosine pyrophosphates, structural analogs of the coenzyme NAD (author's transl)]. [omega-(3-Acetylpyridinio)-n-alkyl]adenosine pyrophosphates are coenzyme analogs of NAD. The adenosine pyrophosphate moiety and the 3-acetylpyridine ring of the analogs are connected by n-alkyl chains of different lengths (ethyl--hexyl). The analogs form strong dissociating complexes with lactate dehydrogenase. The complex formation is predominantly achieved by interaction of the ADP moiety with its respective binding domain at the active site. The redox potentials of the analogs and NAD are of similar magnitude. The coenzyme function of the analogs depends upon the length of the hydrocarbon chain. Lactate dehydrogenase and alcohol dehydrogenases from yeast and horse liver do not catalize hydrogen transfer from their substrates to any other alkyl analog but [4-(3-acetylpyridinio)-n-butyl]adenosine pyrophosphate, aldehyde dehydrogenase from horse liver catalizes hydrogen transfer from acetaldehyde to the pentyl derivative and glyceraldehyde-3-phosphate dehydrogenase catalizes hydrogen transfer to both analogs. In no case, hydrogen transfer from or to one of the 3-acetylpyridine-n-alkyl analogs proceeded with a velocity comparable to NAD or its 3-acetylpyridine analog. The results show that the nicotinamide bound ribose in NAD is involved in the binding and the activation of the coenzyme.


Stimulation of tyrosinase activity and melanin formation of cultured melanoma cells by serum deprivation alone or in combination with dibutyryl cyclic AMP and theophylline. Serum removal from the media of serial monolayer cultures of the Harding-Passey melanoma during an incubation period of 3 days resulted in an exponentially declining DNA synthesis rate (measured by the incorporation of [14C]thymidine) and in an inhibition of cell proliferation. Protein synthesis, as measured by the incorporation of radioactive leucine, was less affected than DNA synthesis. Incubation in serum-free culture medium resulted in significant rises of tyrosinase activity and cellular melanin content. Addition of dibutyryl adenosine 3':5' monophosphate (Bu2cAMP, 5X10(-4) M) and theophylline (5X10(-4) M) to serum-free cultures caused a further striking increase of tyrosinase activity and melanin formation, while treatment of serum containing cultures with Bu2cAMP and theophylline showed only a slight rise in melanogenesis. It is suggested that these stimulatory effects are mediated by an increased intracellular cAMP level, since a correlation between the degree of melanogenesis and cellular cAMP content was indicated. Treatment of serum-free or serum-containing cultures with the phosphodiesterase inhibitor theophylline (5X10(-4)--10(-3)M) alone revealed only a slight enhancement (about 20%) of melanogenesis. Because augmentation of melanogenesis by serum-free medium alone or together with Bu2cAMP and theophylline was prevented by cycloheximide (or actinomycin D), de novo protein synthesis seems to be required for these stimulatory effects.


Enzymatic oxydation of linoleic acid: formation of bittertasting fatty acids. Linoleic acid was oxidized with a protein fraction from soya beans (25 degrees C; 2h), in which lipoxygenase and peroxydase activities occurred. The fatty acids formed were isolated and, after emulsification with a sugar ester, were evaluated for bitter taste. The main components of the bitter-tasting fractions was a mixture of 9.12.13-trihydroxyoctadec-10- and 9.10.13-trihydroxyoctadec-11-enoic acids. The taste threshold lies in the range 0.6-0.9 mumol/ml. Two further trihydroxy-acids and two oxodihydroxy-acids were also identified in the bitter-tasting fraction.


[On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. IX. Influence of bivalent cations on the diphosphatase activity of muscle tissue]. The diphosphatase of comminuted muscle tissue is activated by high MgCl2 concentrations. CaCl2, EDTA and low concentrations of MgCl2 lower the activity. The addition of diphosphate inhibits even after its complete enzymatic hydrolysis the breakdown of additionally added diphosphate; addition of MgCl2 increases the diphosphatase activity again.


[On the enzymatic breakdown of tripolyphosphate and diphosphate in comminuted meat. XII. Influence of the breakdown of tripolyphosphate and diphosphate on the water-holding-capacity of meat (author's transl)]. The increase in the water-holding capacity of salted minced bovine muscle caused by added diphosphate is maintained also after a complete enzymatic breakdown of the diphosphate. This effect is probably due to irreversible dissociation of actomyosin by DP in presence of NaCl.--An increase in water-holding capacity of minced salted bovine muscle after addition of tripolyphosphate occurs only if the tripolyphosphate is enzymatically hydrolysed to diphosphate. In contrast to diphosphate, tripolyphosphate apparently does not cause a dissociation of the actomyosin system.


Dissociation and reassociation of poliovirus. II. Protein components obtained by urea treatment of the virus particle. Dissociation of poliovirus by 9 M urea in 0.015 M NaCl at 25 degrees C resulted in the liberation of 35S RNA and of polypeptides sedimenting at 2S in sucrose gradients containing 9 M urea. However, a ribonucleopolypeptide (RNPP) complex sedimenting at 45S and oligomers of the viral polypeptides sedimenting at 7--8S were found in addition to the monomers sedimenting at 2S when the urea concentration was lowered to 5 M after the dissociation procedure. Ribonuclease treatment prevents the appearance of the RNPP-complex. The amount of the RNPP-complex decreased, when the dissociation was performed at higher ionic strength. Under these conditions small amounts of empty capsids were detected. Polyacrylamide gel electrophoresis showed that the RNPP-complex contained the polypeptide VP1. The oligomers (7--8S) contained the polypeptide VP3 and small amounts of VP2. The bulk of VP2 and some VP3 were found in the 2S position together with VP4. The molecular weight of the dissociation products in urea and phosphate buffer was determined by gel filtration to be about 30,000 for the monomeric polypeptides containing predominantly VP2 and about 70,000 for the oligomeric polypeptides containing predominantly VP3. Our results demonstrate that the oligomers and the RNPP-complex are not primary products obtained by dissociation of the virus particle by urea but are due to a reassociation of the polypeptides or of VP1 and RNA.


[The lymphocyte transformation test in squamous epithelial carcinomas of the orofacial region]. In the last years cell mediated immune reactions against the antigens of human carcinomas have obtained an increasing importance. With the lymphocyte transformation tests was found on the estimate of the PHA (phythemagglutinin)-stimulation a significant difference of the T-cell stimulation of patients with squamous cell carcinoma of the orofacial region opposite to a comparison group of healthy patients.


[Operative treatment of fractures of the patella (author's transl)]. Relative incongruance and great pressure in the femoro-patella joint are, besides the primary traumatic damage of the cartilage, responsible for frequent posttraumatic arthrosis and posttraumatic chondropathy of the patella after patellafracture. An operative reconstruction with a smooth joint surface of the patella is necessary. The only reliable method to fulfil these demands is the tension wire osteosynthesis by Pauwels, which, according to the type of fracture, can be combined with Kirschner wires and small fragment screws. The best access to the patella is established by diagonal incision. Open fractures must and closed fractures should be operated immediately. In comminuted fractures with devitalised cartilagefragments there is no indication to preserve the patella. Primary patellectomy has better results as late patellectomy. According to stability the after-treatment requires 4 to 6 weeks rest in a plaster cast. Although the operation can be performed with technical skill, arthrosis and chondropathy of the patella cannot always be avoided.


The portals of entry of herpes simplex virus infections. In the present paper different possible portals of entry into the body for Herpes simplex Virus are examined. The possibility to infect the cornea with HsV without a preceding scarification was established. Scanning microscopy clearly showed the lesions of the infected cornea and a parallelity between the concentration of the inoculum and the spread of lesions. The i.c., i.m. and i.p. portals of entry are compared as to their capacity to produce encephalitis. The titration of virus may also be realized in the animal experiment. The intragastric portal of entry could be clearly demonstrated. So it is possible to explain herpes encephalitis in human newborns from mothers infected with Herpes virus.


[Detection of viruses in water of the Baltic Sea (author's transl)]. Virological examination of water of the Baltic Sea in the neighbourhood of a sewage outfall was done. By means of an apparatus for concentrating viruses in water, it was possible to detect enteroviruses in four of eleven samples, and in general in those moments, when conditions were fulfilled by a certain windway. The amount of viruses varied from 5 to 126 pfu in 10 liters, the ratio of virus to E. coli titer from 1:11 111 to 1:100 000. Factors influencing the decrease of virus titer in seawater were briefly discussed.


Adenovirus infection in lambs. II. Experimental infection of lambs. Adenovirus strain GY/14 isolated during a natural outbreak was used in experimental infection. Three weeks old lambs responded with temperature rise, respiratory symptoms and diarrhoea to the infection. Infection spread to a contact animal, too. Reisolation of the virus was successful from the nasal discharge and feces from the 3rd to 10th, and the 3rd to 5th day following infection, respectively. In the killed experimental animals the pathological and histological changes observed were similar to those observed in natural cases. On comparing the natural outbreaks with the experimental infection the only difference appeared in the severity of the changes. Following the experimental infection characteristic nuclear inclusions appeared in the nasal and bronchiolar epithelium, in the alveolar septal cells and in the reticular cells of the lymph nodes. Epizootiologic observations and experimental results confirm the assumption that our adenovirus strains isolated from natural cases are pathogenic for lambs.


Experimental infection of calves with an adenovirus isolated from sheep and related to bovine Adenovirus type 2 I. Clinical and virological studies. Colostrum deprived calves were experimentally infected with an adenovirus isolated from sheep and related to bovine adenovirus type 2. The calves showed respiratory symptoms and mild diarrhoea from the third day after infection. Laboratory tests revealed the development of leucopenia, lymphopenia, a drop of the pH of the urine and the appearance of pathological changes in the urine. The animals shed the virus in their nasal discharge, faeces and urine. Comparing the clinical and virological findings with the previous experimental infection of lambs it is concluded, that this type of adenovirus is similarly pathogenic for the two ruminant species.


Overlapping effects of different pituitary hormones on the oogenesis and spermatogenesis of Helix pomatia. In agreement with earlier results, follicle stimulating hormone (FSH) enhances spermatogenesis in the snail. Thyreotropic hormone (TSH), which resembles FSH in its chemical structure, acts in the same way as does adrenocorticotropic hormone (ACTH) to a lesser extent. As opposed to FSH, TSH and ACTH clearly increased the number of mature egg cells. The experiments support the view that the gonad cells of the snails respond to vertebrate hormones, and that the hormones have overlapping effects at this level.


HCG-binding capacity of the rat ovary during pregnancy. During pregnancy, binding of 125I-labelled HCG to the rat ovary increases markedly from the 3rd to the 17th day of pregnancy but is reduced drastically at the end of pregnancy and after delivery. At the 17th day of pregnancy the HCG-binding capacity of the rat ovary is raised 76-fold in comparison to oestrous rats (17th day of pregnancy: 128 X 10(-15) mol/mg wet weight; oestrus: 1.67 X 10(-15) mol/mg wet weight). It is assumed that only LH receptors not occupied by endogenous hormone are covered by our assay. The high number of "free" ovarian HCG receptors during pregnancy apparently represents "Spare" receptors, the functional significance of which remains unclear. It is suggested that the metabolic activity of the ovarian luteal cells during pregnancy is not restricted by the number of HCG receptors present, but through the level of the endogenous gonadotrophic hormone and/or some unknown factors residing in the luteal cell.


Inhibition by somatostatin of mouse thyroid activity following stimulation by thyrotrophin, isoprenaline and dibutyryl cyclic-AMP. The recent discovery of somatostatin-containing cells within the thyroid gland infers that somatostatin may influence thyroid activity. This possibility was investigated by measurements of radio-iodine release in mice pre-treated with 125I and T4. The animals were treated with TSH, isoprenaline or dibutyryl-cyclic AMP with and without concomitant injection of somatostatin. It was found that somatostatin reduced the blood 125I increase in response to each of the three thyroid-stimulating agents. The elimination rates of 125I-labelled T4 and T3 were unaffected by somatostatin. The observations suggests that somatostatin may participate in the regulation of thyroid hormone secretion, by an inhibitory effect exerted within the thyroid gland.


Comparative investigations on cytochemical and cytohormonal exponents of estrogens- progesteron activity in vaginal epithelium in women with complicated pregnancy. I. Threatened abortion. Cytohormonal smears taken from the women hospitalized due to threatened abortion were classified in four groups according to KPI, E.I., FI and CI values. Simultaneously in the vaginal section hormono-dependent enzymes (Al.,P.,Ac.,P., NADH2 t.r., ATP-ase, PAS reaction for glycogen) were studied. The investigated enzymes were compared with the values of cytohormonal indices, in intensity of cytochemical reaction. A distinct correlation was discovered between the intensity of the reactions for Al.,P.,ATP-ase and NADH2 t.r. and KPI, as well as for EI values which suggest either the balance of estrogens-progesteron or its disturbance.


Islet contents of cyclic 3',5'-guanosine monophosphate under conditions which affect the cyclic 3',5'-adenosine monophosphate. The sensitivity of the radioimmunoassay for cGMP was considerably increased by previous 2'-O-succinylation of the nucleotide. The basal content of cGMP in beta-cell-rich pancreatic islets isolated from ob/ob-mice was similar to that of cAMP, i.e. about 3 mumoles per kg dry weight. Extra-cellular Ca2+ was a prerequisite for maintaining this amount of cGMP. The islet cGMP differed from cAMP in being only slightly enhanced or not affected at all when the islets were exposed to high concentrations of glucose, the sulphydryl reagents chloromercuribenzene-p-sulphonic acid and iodoacetamide, or the potent phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine. The data obtained suggest that the turnover rate for cGMP is much slower than that for cAMP in the pancreatic beta-cells. The interrelationships between the two cyclic nucleotides do not seem to fit into a simple pattern of antagonism.


In vitro responses of focal hyperplastic tissue of the human adrenal zona fasciculata to ACTH. The temporal cAMP, cortisol and aldosterone responses to ACTH of focal hyperplasia of the zona fasciculata and of normal human adrenocortical tissue were investigated. ACTH significantly increased cAMP levels (1 min) and cortisol output (2 min) in normal adrenal tissue but not in hyperplastic tissue. However, following ACTH treatment cortisol and aldosterone production were depressed in the abnormal adrenal tissue below the untreated or the ACTH stimulated normal adrenal tissue. In addition, basal cortisol and aldosterone production of the hyperplastic adrenal tissue was elevated above that of the normal adrenal tissue. These findings suggest that the cAMP second messenger concept may be only one of several mechanisms in the modulation of human adrenocortical function.


Biochemical studies on the leukocytes in Chediak-Higashi syndrome. Blood leukocytes from a patient with Chediak-Higashi syndrome (CHS) were compared with normal cells for their capacity of extruding (exocytosis) the lysosomal enzyme myeloperoxidase during phagocytosis or after a treatment with the ionophore A23187 and Ca2+. A decreased rate and extent of exocytosis in phagocytizing CHS cells was observed also with the Ca2+ ionophore. This suggests that a defect in Ca2+ mobilization is not responsible for the impaired secretion of granule content. Isolated granules of CHS cells and of leukocytes were treated with the detergent Triton X-100. Since the solubilization of myeloperoxidase from the CHS granules was much lower than from the normal ones, we suggest that the former organelles have a more resistant membrane.


Coupling of fibrin with low density lipoproteins. By means of chemical methods and immunodiffusion technique it has been shown that low density lipoproteins incorporate into the structure of fibrin clot formed both in purified systems and in the blood plasma. Quantity of the incorporated lipoproteins into the fibrin depends on the concentration of fibrinogen and low density lipoproteins in the blood plasma. Rinsing of the fibrin with solutions of chemical compounds destroying different types of binding show that low density lipoproteins couple with the fibrin clot by means of ion and hydrogen bindings.