Rat tracheal organ culture supports replication of parainfluenza 1 (6/94) virus and promotes 6/94 virus rescue from latently infected human brain cells. Rat tracheal organ culture (TOC) supported replication of parainfluenza 1 (6/94) virus. Cell-associated and cell-free viruses were found after primary infection of TOC. In contrast to other mammalian systems, rat TOC was capable of maintaining 6/94 virus infectivity after primary infection. Rat TOC may be considered a potential indicator system that could be used to detect virus latent in human tissue.


Potentiation of coxsackievirus B3 infection in adult mice pretreated with a gold salt. In mice treated with sodium aurothiomalate (myocrisin), prior to infection with Coxsackievirus B3, 90% of the animals died by the 11th day postinfection (p.i.). A mortality of 10% was noted in mice receiving myocrisin only, and no deaths occurred in animals infected with virus alone. The highest amount of virus was recovered from the pancreas of myocrisin-treated mice on day 3 p.i. This was over 500-fold higher than the virus titer found in the pancreas of mice infected with virus only. Generally the titer of virus present in different organs was higher at every point in drug-treated animals as compared to intact mice infected with the virus. A high and persistent viremia was present in myocrisin-treated mice; in contrast a low viremia followed by virus clearance from the blood was observed in intact mice infected with the virus. The antibody response was studied in intact and myocrisin-treated mice infected with the virus. In both groups, no neutralizing antibodies were detected on days 1, 2, and 3 p.i. On day 7 after infection, the titers of antibodies were 1:16 and 1:12 in intact and myocrisin-treated mice, respectively. Administration of hyperimmune anti-Coxsackievirus B3 serum 6 hours after infection protrected in myocrisin-treated group of mice against lethal disease. The results of these studies suggest that (1) antibodies alone may not be sufficient to limit the spread and persistence of virus in natural infections and (2) in the absence of any apparent histopathological differences the increased multiplication of Coxsackievirus B3 could be the cause of death in myocrisin-treated mice.


A case of Coxsackie A9 virus infection with orchitis. A thirteen-year-old boy with bilateral orchitis was diagnosed as being infected by Coxsackie A9 virus by isolation of the virus from a throat swab and a fecal specimen. Serologic investigations revealed the development of transitory specific neutralizing IgM antibodies against the isotate and of persistent antibodies belonging to the other immunoglobulin classes. An etiology of the orchitis by any of the infectious agents usually found with this condition could be excluded.


Reduction of herpes simplex virus-type 2 plaque formation by urea. The effect of urea on plaque formation by herpes simplex virus type 2 (HSV-2) was examined in two systems at concentrations within or approximating the range found in human urine. Approximately 7--10 mg urea/ml, added 2, 4, or 8 hours after infection, reduced plaque formation by 50% in African green monkey kidney cells. The growth of this system was affected slightly by continuous treatment with urea at 7--10 mg/ml. Plaque formation was reduced in the monkey kidney system, albeit diminishingly, even after addition of urea 12 hours after infection. In the human lung fibroblast system, urea at 10 mg/ml reduced plaque numbers by 50% but depressed the growth of cells completely.


Effects of antidepressant agents on the synthesis of brain monoamines. The effect of seventeen established or possible antidepressant agents on the synthesis of 5-HT, noradrenaline and dopamine in rat brain has been investigated by measuring the accumulation of 5-hydroxytryptophan and DOPA induced by an inhibitor of the aromatic L-aminoacid decarboxylase (3-hydroxybenzylhydrazine hydrochloride, 100 mg/kg i.p.). All the established inhibitors of 5-HT, noradrenaline and dopamine uptake were found to inhibit the synthesis of the respective monoamines, presumably by influencing a receptor-mediated feedback mechanism. A close correlation appears to exist between blockade of transmitter uptake and inhibition of transmitter synthesis. The results support current ideas on the mode of action of antidepressant agents.


Painful legs and moving toes: evidence on the site of the lesion. A condition of painful legs with moving toes was described in 1971. Further examples of this condition are now reported, showing lesions in the posterior root ganglion, cauda equina, nerve roots, or a peripheral nerve of the lower limb. It is concluded that this syndrome is caused by a lesion of the afferent fibres of the posterior nerve roots. It is likely that this lesion causes frequent spontaneous impulses in the posterior roots which activate local circuits of interneurones and motoneurones and result in co-ordinated movements involving local muscles.


Muscle hypertrophy with neuropathy.

Muscle hypertrophy with neuropathy. A patient with insidious onset of weakness, muscle atrophy and true hypertrophy, and sustained spasms is described. The spasms, initially mistaken to be myotonic, were shown electromyographically to result from sustained activity of the muscle fibres. An additional clinical manifestation verified myographically, was impaired reciprocal inhibition. Also, the patient had thick peripheral nerves and very slow motor (but normal sensory) nerve conduction. Histologic examination of sural nerve biopsy revealed large vacuoles within Schwann cells containing unidentified material, as well as onion-bulb formations. The possibility of a metabolic error resulting in storage of an abnormal material within Schwann cells is assumed.


Computerized double-tracer subtraction scanning with gallium-67 citrate in inflammatory diseases. A gallium-67/technetium-99m subtraction technique was used with a variable weighting factor. That is, each image was separately set to 100%. Varying amounts of the Tc-99m images were subtracted from those of Ga-67. A total of 95 patients who had radiogallium scanning for suspected inflammatory disease were studied by the subtraction technique. Thirty of these patients had abnormal Tc-99m pyrophosphate bone scans, while 20 had abnormal radiogallium abdominal foci; 45 had defects in liver, spleen, or kidney images. The subtraction technique with variable weighting was highly successful in enhancing hot-spot visibility, and in providing information as to the anatomic location of the defect.


Vitamin E and lipoprotein levels in the sera of pregnant women. The serum levels of vitamin E, cholesterol and lipoproteins, alpha1-lipoproteins and beta-lipoproteins in pregnant women were investigated. It was found that serum vitamin E, cholesterol and the lipoproteins had a tendency to increase throughout gestation. The mean serum alpha1-lipoprotein concentration was higher in pregnant women than in healthy control women. The ratios of the vitamin E concentration to the sum of alpha1-lipoproteins and beta-lipoproteins concentration in sera was constant. Furthermore, it was  found that serum vitamin E was correlated closely to the lipoprotein content (r = 0.814, p less than 0.001), except in a few subjects with abnormally high vitamin E levels.


Non-fibrous mineral dusts and malignant tumors: an epidemiological study of mortality. The connection between enhanced oncological risk and the exposure to non-fibrous mineral dusts receives a contradictory but mostly negative estimation in the literature. The present authors estimated the death rate by relating the number of deaths from cancer, registered at different companies during a 21 to 27-year span, to the number of man-years of work for all employees during the same period. The death rates, calculated as above, were compared with the age standardized analogous death rates of the control population. The ratio of these indices, which statistically significantly exceeded 1.0, was taken as evidence of risk connected with exposure to the industrial environment. Frequency of registration of deaths from malignant tumors among other causes of death of silicotic patients was also studied. The results are in favor of accepting talc dust (even that not containing fibrous minerals) as a carcinogen, and silica containing dust only as a cocarcinogenic agent. The percent silica content in dust either plays no role at all, or plays a much lesser role than the total dust load. Tbc as the competing cause of death in silicotic patients, in grave forms of the disease, eliminates the susceptibility of patients to death from cancer.


Pancreatic adenomas in infants and children: current surgical management. Islet cell adenomas are an important consideration in infants and children with hypoglycemia due to hyperinsulinism. Between 1965 and 1977, 32 patients with hyperinsulinism were seen at the Children's Hospital of Philadelphia. Sixteen of these patients underwent surgery. Eight patients had single pancreatic adenomas, 5 of whom were infants under 1 yr of age. In 3 infants an adenoma was recognized and removed at the time of surgery. In 4 patients a subtotal pancreatectomy was successful in removing the adenoma. One infant is whom the adenoma was not included in the subtotal pancreatectomy died postoperatively with intractable hypoglycemia. Of the 7 patients cured by surgery, 6 are normal and 1 has brain damage due to delay in treatment of hypoglycemia. One child has mild diabetes. A combined medical and surgical protocol has been developed that permits rapid diagnosis of hyperinsulinism and selection of candidates for surgery. Infants under 1 yr of age who fail to respond to diazoxide should be explored. In children whose hyperinsulinism appears beyond 1 yr of age, surgery is indicated, since an adenoma is likely.


Reimplantation of the ampulla of Vater after total pancreatectomy for nesidioblastosis. Total pancreatectomy is often required to control hypoglycemic seizures in infants with nesidioblastosis. If duodenal devascularization results, reconstruction is difficult because standard biliary-intestinal anastomoses may reflux, or, in infants, become strictured. Therefore, surgeons are loath to perform such procedures. To avoid these complications, the common bile duct and the ampulla of Vater were implanted into the reconstructed duodenum.


Preoperative angiographic embolization for large hemorrhagic Wilms' tumor. Preoperative angiographic embolization of the renal artery is a surgical adjunct not necessary for the majority of Wilms' tumors. However, on the basis of early experience, we would recommend this technique for those large vascular tumors with preoperative hemorrhage in which the risk of embolization is likely to outweight the risk of intraoperative disruption and hemorrhage.


The pharmacology of 2,3-dimercaptosuccinic acid and its potential use in arsenic poisoning. Arsenic (As2O3)-poisoned rats were treated with either 2,3-dimercaptosuccinic acid (DMS) or dimercaptopropanol (BAL) at doses of 30 mg/kg/day. A control group received no treatment. The total quantity of arsenic excreted was not significantly different in response to 4 days of treatment with either DMS or BAL. In addition, there was no difference between the two drug treatment groups in the residual arsenic content of brain, liver, kidney and spleen after treatment. Both drugs reduced the arsenic content of each tissue to approximately 40% of that of untreated controls. Previous studies have shown that DMS is orally effective for the treatment of lead poisoning. The LD50 of DMS was determined to be in excess of 3 g/kg in rats and mice, approximately 30 times the LD50 of BAL. No gross, histopathological or biochemical evidence of toxicity was observed in mice, rats or dogs which received DMS 5 days per week for 6 months. DMS did not affect the excretion of zinc, iron, calcium or magnesium. Urinary copper excretion was significantly elevated in response to 30 mg/kg of DMS, suggesting that the drug might also be useful for the treatment of Wilson's disease.


Depression of spinal monosynaptic transmission by diethyl ether: quantal analysis of unitary synaptic potentials. The site at which diethyl ether impairs transmission in the spinal monosynaptic pathway was studied by intracellular recording from lumbosacral motoneurons. The drug was administered by inhalation to spinal cats, in concentrations which produce surgical anesthesia. Ether had no significant effect on resting potential or input resistance of the cell membrane. It decreased the electrical excitability in some but not all motoneurons. This action may contribute to the depressant effects of ether. Monosynaptic excitatory postsynaptic potentials evoked by impulses in a single Ia afferent fiber (unitary EPSPs) of the triceps surae nerve were recorded from homonymous motoneurons. They were measured and their amplitude distribution was analyzed by a computer-aided procedure. The mean amplitude of the unitary EPSPs was 0.15 to 0.31 mV, and the mean number of transmitter quanta released by each impulse ranged from 1.5 to 4.1 before drug administration. Both values were decreased during inhalation of ether but recovered toward normal after the drug was discontinued. The mean amplitude of the EPSPs produced by one transmitter quantum was 0.08 to 0.15 mV and was not depressed during ether administration. It is concluded that either in anesthetic concentrations depresses synaptic potentials presynaptically by decreasing the amount of excitatory transmitter released, while leaving the chemosensitivity of the postsynaptic membrane unchanged.


Opiate receptor agonists as modulators of gamma-aminobutyric acid turnover in the nucleus caudatus, globus pallidus and substantia nigra of the rat. The injection of various doses of morphine, subcutaneously, or of beta-endorphin, intraventricularly, changes the turnover rate of gamma-aminobutyric acid (TRGABA) in the substantia nigra, globus pallidus and nucleus caudatus. The TRGABA decreases in N. caudatus but increases in globus pallidus and substantia nigra. These changes are dose related and can be inhibited by naltrexone. The increased TRGABA in globus pallidus elicited by these opioid receptor agonists may be associated with catalepsy since muscimol, a specific GABA receptor agonist, injected into the globus pallidus causes a dose-related catalepsy. Since this GABA receptor agonist injected into the substantia nigra fails to cause catalepsy, one can exclude that the increase in the TRGABA of substantia nigra elicited by opiate receptor agonists is operative in mediating the catalepsy elicited by opioids.


Interaction between alpha adrenergic and serotonergic activation of canine saphenous veins. Serotonin and norepinephrine produced concentration-dependent contractions of helical strips of canine saphenous veins. The contractile responses to both agonists were inhibited by the alpha adrenergic receptor blocking agent phentolamine. Tolazoline inhibited the contractile responses of canine saphenous veins to norepinephrine but augmented those to serotonin. Blockade of adrenergic neuronal reuptake with cocaine enhanced the sensitivity of the canine saphenous vein to serotonin, but did not suppress the inhibition by phentolamine of the contractile responses to this indolealkylamine. Serotonin-mediated venoconstriction was not secondary to release of norepinephrine since it was not accompanied by an increased release of [7-3H]-norepinephrine. These findings suggest that serotonin does not contract canine saphenous veins by stimulation of typical serotonergic receptors. The binding sites for serotonin and norepinephrine in cutaneous venous smooth muscle may share part of a common receptor complex, which triggers the contractile process. Alternatively, serotonin and norepinephrine may act at two different receptors to elicit contraction of canine saphenous veins.


Studies on SK&F 29661, an organ-specific inhibitor of phenylethanolamine N-methyltransferase. SK&F 29661 is an effective, reversible inhibitor of both central nervous system and adrenal phenylethanolamine N-methyl-transferase in vitro; its Ki values in our standard assay systems were 6 X 10(-7) M (central nervous system) and 3 X 10(-7) M (adrenal), respectively. In vivo, the drug inhibited the conversion of [3H]norepinephrine to [3H]epinephrine in the rat adrenal gland and upon chronic administration decreased the endogenous adrenal epinephrine/norepinephrine ratio in both the rat and squirrel monkey. SK&F 29661 did not, however, reduce rat brain stem PNMT activity after systemic administration; subsequent radioautographic studies indicated that the compound did not enter the central nervous system, presumably because of its high polarity. This drug may be useful in defining the physiological importance of peripheral phenylethanolamine N-methyltransferase inhibition.


Transmission blockade and stimulation of ganglionic adenylate cyclase by catecholamines. Isolated rat superior cervical ganglia treated with isoproterenol and related drugs show an increase in ganglionic cyclic adenosine 3':5'-monophosphate (cAMP) and a block of transmission. For isoproterenol, the maximum increase in cAMP occurred at 1 X 10(-6) M, a concentration without effect on transmission. Approximately 5 X 10(-4) M isoproterenol was required to reduce the ganglionic compound action potential by 50%. Dopamine, in  contrast to isoproterenol, had no effect on the content of cAMP but depressed transmission. The maximum increase in cAMP produced by norepinephrine occurred with 5 X 10(-4) M, a concentration that reduced transmission by approximately 35%. The effects of isoproterenol on adenylate cyclase and transmission were prevented either by practolol (10(-4) M) or phentolamine (10(-5) M). Dopamine-induced blockade of transmission was antagonized by phentolamine (10(-5) M). Whereas the blockade of transmission by norepinephrine was antagonized by practolol (10(-5) M) or phentolamine (10(-5) M), the stimulation of adenylate cyclase by norepinephrine was prevented by practolol (10(-4) M) but not by phentolamine (10(-5) M). These results show that the blockade of transmission and stimulation of adenylate cyclase are unrelated in rat ganglia and that adrenergic receptor classification is ambiguous. The role of adenylate cyclase in ganglia is unclear.


Effects of acute and continuous morphine administration on catecholamine-sensitive adenosine triphosphatase in mouse brain. The catecholamine-stimulated adenosine triphosphatase (ATP-ase) activities in mouse brain synaptosomes were inhibited by morphine both in vitro and in vivo. Morphine up to 10(-3) M had no effect on basal ATPase activities but at 10(-4) M significantly inhibited dopamine-sensitive ATPase activities in vitro. The morphine effect was antagonized by an opiate antagonist, naloxone. The catecholamine-sensitive ATPase activities were also inhibited by acute administration of morphine. The inhibition was dose-dependent. However, naloxone partially antagonized the morphine inhibition of depamine-sensitive ATPase activity but not norepinephrine-sensitive ATPase activity. A significant decrease in the sensitivity of synaptosomal ATPase to catecholamines was observed in mice rendered tolerant by morphine pellet implantation. The Na+,K+-ATPase was more affected by morphine as compared to Mg++-ATPase activity. The dopamine-sensitive Na+,K+-ATPase activity was restored by 50% in precipitated withdrawal mouse brain synaptosomes. Norepinephrine-sensitive ATPase activity was also restored partially in precipitated withdrawal animals. These results suggest that in mouse brain synaptosomes morphine may be interacting with ATPase at or near the catecholamine-active sites.


Nervous release of vasoactive intestinal polypeptide in the gastrointestinal tract of cats: possible physiological implications. 1. The release of vasoactive intestinal polypeptide (VIP) into blood from the gastrointestinal tract was studied when eliciting autonomic nervous effects known to be mediated via non-adrenergic, non-cholinergic nerve fibres. All studies were performed on animals given atropine. 2. Electrical stimulation of the low threshold vagal fibres to the stomach did not significantly change gastric volume or VIP concentration in the venous effluent from the stomach. Stimulating the high threshold fibres, on the other hand, produced a gastric relaxation concomitant with a significant increase of venous plasma VIP concentrations. When eliciting a similar vagal relaxation of the stomach by distending a balloon the oesophagus a significant increase of venous plasma VIP concentration was also recorded. 3. Mechanical stimulation of the mucosa of the small bowel increased intestinal blood flow and a significant increase of venous plasma VIP concentration was observed. 4. Stimulation of the pelvic nerves to the colon produced a transient vasodilation and a significant increase of VIP in the venous effluent from the large bowel. A maintained vasodilation in the colon was induced by mechanically stimulating the rectal mucosa. This vascular response was accompanied by a significant raise of venous plasma VIP concentration. 5. The results demonstrate that all the studied nervous effects known to be mediated via non-adrenergic, non-cholinergic nerve fibres were accompanied by significant increases of the VIP concentration in the venous effluent. The possible physiological implications of these findings are discussed and it is proposed that VIP may be a neurotransmitter in the gastrointestinal tract.


Facilitation of synaptic transmission by general anaesthetics. 1. The actions of five structurally different intravenous and inhalation anaesthetics (alphaxalone/alphadolone, halothane, ketamine, methohexitone, and pentobarbitone) have been studied on synaptic transmission through the cuneate nucleus of the dorsal column-lemniscal afferent pathway in the decerebrate cat. 2. Synaptic input and output were estimated from antidromic and orthodromic potentials, which were evoked by either afferent volleys from the periphery or micro-electrode excitation of the presynaptic fibre terminals in the cuneate and recorded at forelimb nerves and the medial lemniscus. 3. Each of the anaesthetic agents potentiated the efficiency of synaptic transmission, as shown by the elevation of input-output curves constructed from the integrals of the potentials evoked by varying intensities of either peripheral or cuneate stimulation. 4. The excitability of the afferent terminals, as measured at the peripheral nerves by the antidromic responses to micro-electrode stimulation, was depressed by the anaesthetics. Post-synaptic excitability, which was assessed from the direct lemniscal response to intra-nuclear stimulation, did not appear to change. 5. Hypotensive states (mean arterial levels less than 60 torr) produced depolarization of presynaptic terminals and depression of synaptic efficiency and transmission; these changes opposed the primary effects of the general anaesthetics. 6. It is concluded that anaesthetics do not depress activity at all synapses of the central nervous system. Their facilitatory action on cuneate transmission is attributed to an enhanced release of excitatory transmitter; the underlying mechanism may be hyperpolarization of the primary afferent terminals, secondary to an increase in K+ conductance.


Role of joint afferents in motor control exemplified by effects on reflex pathways from Ib afferents. 1. Intracellular recording from motoneurones to hind limb muscles in the cat was used to investigate the effect of volleys in the posterior nerve to the knee joint on motoneurones and on transmission from Ib afferents. 2. Volleys in the joint nerve facilitate transmission in disynaptic and trisynaptic inhibitory and excitatory reflex pathways from Ib afferents. It is postulated that facilitation, which appears at a strength of 1.5 times threshold, is evoked, not by Ib afferents which 'contaminate' the joint nerve, but by afferents from joints receptors. 3. T;e time course of facilitation of the disynaptic Ib i.p.s.p.s in motoneurones indicates that these joint afferents have disynaptic connexions with the interneurones of the Ib inhibitory pathway. 4. A brief description is given of synaptic effects evoked in motoneurones by graded electrical stimulation of the posterior nerve to the knee joint. At low stimulus strength the effects may be evoked via interneurones of Ib reflex pathways, but some results suggest that other interneuronal paths are utilized as well. Somewhat higher strengths, but occasionally less than 2 times threshold, produce later synaptic effects presumably mediated by reflex paths from the flexor reflex afferents; it does not seem likely that the contributory afferents in the joint nerve have nociceptive function. 5. It is suggested that impulses from impulses from joint receptors can influence tension regulation from Golgi tendon organs; if these receptors are activated in the terminal phase of the movement they may contribute a purposeful decrease of tension. It is pointed out that joint receptors may have an important role in motor regulation by their effects on interneurones of the different neuronal systems controlling motoneurones.


The use of cattle to protect sheep from bluetongue infection. Studies on the host preferences of Culicoides imicola, the vector of bluetongue virus in South Africa, are reviewed. There is agreement that this species prefers to feed on cattle but will also feed on other bovidae and sheep. Over a seven year period cattle kept near sheep on a Natal farm appear to have appreciably reduced the incidence of bluetongue in the sheep. In addition to immunization this "decoy" approach is therefore recommended to assist in the protection of stock from insect borne diseases such as bluetongue and possibly African horsesickness and Rift Valley fever.


[Infectious causes of perinatal mortalities in ruminants (author's transl)]. The advantages and disadvantages of the different diagnostic techniques e.g. pathological and microbiological studies, immunoglobulin and specific antibody determinations and fluorescent antibody studies in relation to these mortalities are discussed. The most important pathological lesions in the placentas and foetuses are described.


The mitochondria-rich cell of frog skin as hormone-sensitive "shunt-path". Further investigations about the role of the mitochondria-rich cell (MR cell) in hormone-mediated transport regulation in the epithelium of frog skin brought the following results: Unlike toad bladder, in frog skin the spontaneous potential difference cannot be reversed when Na transport is blocked. A similar situation is obtained when, in addition to transport-blockade, one applies a chemical gradient for chloride to the epithelium. Under these conditions we found that in the intact preparation as well as in the separated epithelium: (i) the reversed current (RC) is linearly related to the number of MR cells; (ii) RC is mainly carried by a passive, transcellular chloride flux inwards and (iii) RC is sensitive to nor-adrenaline (10(-7) M). The beta-blocker propranolol abolishes this effect. We propose that the MR cells are the sites of transepithelial shunt-path and that this chloride flux is transcellular. As it is hormone sensitive, it could be an important regulatory instrument for the regulation of overall salt transport (internal shorting).


Role of prostaglandin E (PGE) in the modulation of the action of vasopressin on water flow in the urinary bladder of the toad and mammalian kidney. PGE1 and PGE2 are known to interfere with the water permeability effect of vasopressin in toad bladder and kidney. It has been proposed that endogenous prostaglandin E (PGE), synthesized within cells of vasopressin-sensitive tissues, serves to modulate the permeability changes elicited by the neurohypophyseal hormone. Direct evidence in support of this hypothesis is as follows: vasopressin increases the biosynthesis of PGE2 in renal interstitial cells and in isolated toad bladder. In the latter, inhibition of vasopressin-induced synthesis of PGE by a variety of inhibitors results in a greater water permeability response to vasopressin. It appears that vasopressin has two effects in toad bladder and kidney: (i) it activates adenylate cyclase thereby increasing the concentration of adenosine 3',5' monophosphate  (cyclic AMP), the nucleotide responsible for the resultant increase in water permeability; and (ii) it activates a phospholipase that serves to release arachidonic acid, the precursor of PGE2 from intracellular pools. The PGE derived from the arachidonic acid diminishes adenylate-cyclase activity, in consequence of which the response of the enzyme to vasopressin is modulated.


Photoaffinity labeling of the antidiuretic hormone receptor. A study to determine the feasibility of photoaffinity labeling the antidiuretic hormone receptor in the toad urinary bladder has been carried out. Two photoactivated derivatives of oxytocin have been synthesized, purified, and characterized chemically and biologically. Photolysis of the toad bladder in the presence of one of these derivatives, 2-nitro-5-azidobenzoylglycyloxytocin, produces a permanent inhibition of the response to native oxytocin. This inhibition can be relieved by protecting the hormone receptor with excess oxytocin during the photolysis. These results suggest that the photolysis-dependent inhibition of the response to native hormone is due to covalent incorporation of the photoaffinity label into the hormone receptor.


Characteristics of antibody inhibition of rat kidney (Na+ -K+)-ATPase. Antibodies which were raised against highly purified membrane-bound (Na+ -K+)-ATPase from the outer medulla of rat kidneys inhibit the (Na+-K+)-ATPase activity up to 95%. The antibody inhibition is reversible. The time course of enzyme inhibition and reactivation is biphasic in semilogarithmic plots. In the purified membrane-bound (Na+-K+)-ATPase negative cooperativity was observed (a) for the ATP dependence of the (Na+ -K+)-ATPase activity (n = 0.86), (b) for the ATP binding to the enzyme (n = 0.58), and (c) for the ouabain inhibition of the (Na+ -K+)-ATPase activity (n = 0.77). By measuring the Na+ dependence of the (Na+ -K+)-ATPase reaction, a positive homotropic cooperativity (n = 1.67) was found. As reactivation of the antibody-inhibited enzyme proceeds very slowly (t0.5 = 5.2 hr), it was possible to measure characteristics of the antibody-(Na+ -K+)-ATPase complex: The antibodies exerted similar effects on the ATP dependence of the (Na+ -K+)-ATPase reaction and on the ATP binding of the enzyme. Vmax of the (Na+ -K+)-ATPase reaction and the number of ATP binding sites were reduced while K0.5 ATP for the (Na+ -K+)-ATPase activity and for the ATP binding were increased by the antibodies. The Hill coefficients for the ATP binding and for the ATP dependence of the enzyme activity were not significantly altered by the antibodies. The antibodies increased the K0.5 value for the Na+ stimulation of the (Na+ -K+)-ATPase activity, but they did not alter the homotropic interactions between the Na+-binding sites. The negative cooperativity which was observed for the ouabain inhibition of the (Na+ -K)-ATPase activity was abolished by the antibodies. The data are tentatively explained by the following model: The antibodies bind to the (Na+ -K+)-ATPase from the inner membrane side, reduce the ATP binding symmetrically at the ATP binding sites and reduce thereby also the (Na+ -K+)-ATPase activity of the enzyme. The antibodies may inhibit the ATP binding by a direct interaction or by means of a conformational change at the ATP binding sites. This may possibly also lead to the alteration of the Na+ dependence of the (Na+ -K+)-ATPase activity and to the observed alteration of the dose response to the ouabain inhibition.


Twice-a-day treatment in the radiotherapeutic management of malignant mixed tumor of the parotid gland: A case report. A patient with a 2,300 gm malignant mixed tumor of the parotid gland had recurrence 19 days post surgery. The recurrent mass failed to respond to daily fractions of 200 rad conventional irradiation four times per week and actually increased in size. A superfractionation scheme was substituted, employing twice-a-day 200 rad at 4-5½ hours intervals three times a week for 2½ weeks. At the completion of treatment, there was a 50 percent regression of the recurrent tumor mass and a 100 percent regression two weeks post irradiation. A protocol using a twice-a-day treatment is discussed.


Peptide-chain initiation with Lsc poliovirus is intrinsically more resistant to hypertonic environment than is peptide-chain initiation with Mahoney virus and deletion mutants of Mahoney virus. Peptide-chain initiation with LSc poliovirus was more resistant to hypertonic medium than peptide-chain initiation with Mahoney poliovirus. Protein synthesis of LSc virus retained its relative resistance to high osmolarity created by the addition of excess NaCl to the medium in cells coinfected with Mahoney virus. The data indicate that peptide-chain initiation with LSc virus is intrinsically more resistant to high osmolarity than that of Mahoney virus rather than reflecting different permeability changes in cells after infection. Two Mahoney virus mutants harboring deletions at the 5' end of the viral chromosome exhibited the same sensitivity to excess NaCl as parent virus, suggesting that the original chromosomal region for peptide-chain initiation has not been severely altered by the deletions.


Specific site of action for single-strand specific nuclease on the double-stranded circular DNA intermediates of an avian RNA tumor virus. Circular viral DNA intermediates obtained from the quail tumor line, QT6, at 1 day after infection, were opened at one specific location by the single-strand specific nuclease, S1, of Aspergillus oryzae. This site was no longer accessible to the S1 nuclease when circles were first opened at another location with a restriction endonuclease.


Detection of mouse mammary tumor virus RNA in BALB/c tumor cell lines of nonviral etiologies. A complementary DNA (cDNA) probe to mouse mammary tumor virus (MMTV) RNA was synthesized using calf thymus DNA oligonucleotides as a random primer. This probe was then used to study the expression of MMTV RNA in cell lines from BALB/c tumors induced in vivo either spontaneously or in response to viral, chemical, or hormonal stimuli. The cDNA had a length of approximately 400 to 500 nucleotides and specifically hybridized to MMTV RNA and BALB/c lactating mammary gland RNA, but not to Moloney leukemia virus RNA. Calf thymus DNA-primed cDNA could protect 50% of iodinated MMTV RNA from S1 nuclease digestion at cDNA-RNA ratios of 1:1 and 90% of labeled viral RNA at ratios of 10:1. Thermal denaturation of MMTV RNA-cDNA hybrids yielded a T(m) of 88.5 degrees C, indicative of a well-base-paired duplex. Screening of mouse mammary tumor cells for MMTV sequences revealed that three out of five lines of BALB/c origin had undetectable levels of viral RNA (<three molecules per cell) by RNA excess hybridization. Two of the three "virus-negative" cell lines were derived from tumors induced by the chemical carcinogen 7,12-dimethylbenz(alpha)anthracene, whereas the third tumor occurred spontaneously. Two lines from tumors induced by either viral (mammary tumor virus) or hormonal (17-beta-estradiol) stimulus contained between three and nine molecules of MMTV RNA per cell by both RNA excess and cDNA excess hybridization. Clonal derivatives of these tumor lines had levels of viral RNA comparable to those of their parental lines. Therefore, it appears that the presence of detectable MMTV RNA sequences is not a necessary requirement for the maintenance of all murine mammary gland neoplasias.


Genomic stability of gibbon oncornavirus. The 70S RNAs from several gibbon type C viruses were examined for sequence homology by molecular hybridization using complementary DNA probes. The sequence homology was found to vary with each virus isolate. The genome from one isolate was examined for genomic stability after the virus was experimentally passaged through three unrelated gibbons. The genomic homology remained unchanged after three passages, having greater than 93% homology based on complementary DNA-70S RNA hybridization and melting temperature analysis of the duplex. The genome from another isolate was similarly found to be unchanged after the virus was naturally transmitted in gibbons. The genomic variation found in the various isolates is not the consequence of recent horizontal transmission from a common virus.


Transcription pattern of in vivo-labeled late simian virus 40 RNA: equimolar transcription beyond the mRNA 3' terminus. We have examined the pattern of RNA transcription on the L (late) DNA strand late in the simian virus 40 virus infectious cycle by separating pulse-labeled RNA chains according to size and hybridizing to an ordered series of DNA fragments obtained by restriction enzyme digestion. From this analysis, the 5' end of the nascent transcript occurs a short distance counterclockwise from 0.735. Transcription proceeds in a clockwise direction. There is equimolar transcription for at least 1,000 nucleotides beyond the 3' end of the mRNA (0.175). The 3' terminus for the largest molecules is in 0.43--0.655. Molecules which represent more than one circuit of the genome are not more than 1% of the total population of nascent molecules. Implications of these findings for models of the biogenesis of mRNA are discussed.


Analysis of unintegrated avian RNA tumor virus double-stranded DNA intermediates. Previous studies by Guntaka et al. have shown that the unintegrated DNA intermediates of avian RNA tumor virus replication can be readily isolated from cultures of the quail tumor line QT-6 at 1 day after infection. The intermediates include double-stranded linear and covalently closed circular DNA species. Using the analysis procedure of Southern together with previously obtained information regarding the sites of action of certain restriction endonucleases on avian sarcoma virus DNA, we have further characterized the viral DNA intermediates. Evidence is presented that, relative to the RNA genome, most of the linear species possess a direct terminal sequence redundancy equivalent to 0.5 X 10(6) +/- 0.3 X 10(6) daltons of double-stranded DNA. Some of the circular forms also possess a sequence redundancy of 0.21 X 10(6) +/- 0.03 X 10(6) daltons.


Specificity of cell surface virus receptors on radiation leukemia virus and radiation-induced thymic lymphomas. We have developed a system for analysis of murine leukemic virus (MuLV) receptors on the surface of thymic lymphoma cells utilizing the fluorescence-activated cell sorter. The binding of fluoresceinated or rhodaminated MuLV to target cells showed saturation kinetics and was blocked by homologous MuLV, and bound MuLV had a polypeptide profile identical to that of input MuLV. Thymic lymphomas bound specifically the MuLV which induced them, whereas only 0.5 to 2% of normal thymocytes showed equivalent MuLV binding. Simultaneous binding of excess fluoresceinated RadLV and rhodaminated MCF-247 AKR virus to radiation leukemia virus-induced or spontaneous AKR thymic lymphomas demonstrated that even in the presence of both viruses the cells bound preferentially the inducing MuLV. Examination of the C57BL/Ka endogenous viruses showed that radiation leukemia virus-induced thymic lymphomas bind only thymotropic-leukemogenic radiation leukemia virus and not eco- or xenofibrotropic MuLV's. Thus, virus binding in this system involves only leukemogenic isolates of these retroviruses and implies a central role of this receptor-ligand interaction in the processes of leukemic transformation.


Physical mapping of BK virus DNA with SacI, MboII, and AluI restriction endonucleases. A new restriction endonuclease, SacI from Streptomyces achromogenes cleaves BK virus (strain MM) DNA into 3 fragments, whereas MboII from Moraxella bovis and AluI from Arthrobacter luteus give 22 and 30 fragments, respectively. All these specific DNA fragments were ordered and mapped on the viral genome by two methods first, by the reciprocal digestion method using uniformly 32P-labeled DNA; and second, by the partial digestion technique using the single-end 32P-labeled DNA. This study, together with those reported earlier, defined the location of 90 cleavage sites on the BK virus DNA.


Extent of transcription of the E strand of polyoma virus DNA during the early phase of productive infection. Early polyoma virus-specific RNA, in nuclei and cytoplasm of cells labeled with [(3)H]uridine, was analyzed by hybridization with filter-bound Hpa II fragments of polyoma DNA. About 40% of labeled cytoplasmic virus-specific RNA hybridized with Hpa II fragment 2, which represents about 40% of the region coding for E-strand mRNA's; less than 5% hybridized with fragments 1 or 3, which lie outside this region. A somewhat lower proportion (about 30%) of labeled nuclear virus-specific RNA hybridized with fragment 2, and a small but significant fraction (7 to 14%) hybridized with fragments 1 and 3. About two-thirds of the nuclear RNA which hybridized to fragment 1 was complementary to the E strand, and one-third was complementary to the L strand. Results did not vary greatly in samples labeled for periods of from 15 min to 3 h. The major species of pulse-labeled nuclear polyoma-specific RNA sedimented at 22S and thus is slightly larger than the 19S cytoplasmic mRNA. These results show that most early nuclear RNA ( approximately 75%) is transcribed from the region of the E strand, which codes for early mRNA's, and that there is probably a site at which transcription is terminated at the end of this region. However, a small amount of early nuclear RNA ( approximately 15%) is transcribed from the remainder of the E strand, perhaps by readthrough of this termination signal. In addition, there is a small amount of transcription from the L strand, whose significance is unclear. Neither the L-strand transcripts nor the nonmessenger E-strand transcripts are transported to the cytoplasm.


Cell-free translation of purified virion-associated high-molecular-weight RNA synthesized in vitro by vaccinia virus. Virion-associated high-molecular-weight (HMW) RNA synthesized in vitro by purified vaccinia virus particles has been translated in a wheat germ cell-free protein synthesizing system. Purified HMW RNA directs the synthesis of translation products which are identical to the translation products made in response to in vitro-synthesized, virion-released 8 to 12S mRNA. The translation of HMW RNA proceeds exclusively through a 5'-terminal cap-mediated initiation step. Furthermore, only one coding sequence is translated per HMW RNA molecule, and that sequence is probably located near the 5' end of the molecule. These conclusions are based on the following results. (i) Sodium dodecyl sulfate--polyacrylamide gel electrophoresis patterns of translation products synthesized in response to HMW RNA and in response to 8 to 12S mRNA were qualitatively identical. (ii) On an equal weight basis, HMW RNA was 25 to 30% as active as 8 to 12S mRNA in stimulating in vitro protein synthesis. (iii) Unmethylated HMW RNA was translated at 10% the efficiency of the methylated form of this RNA. (iv) m7pG inhibited the translation of fully methylated HMW RNA by 90%. (v) After the initiation step of translation was blocked by aurintricarboxylic acid, the rate with which amino acids were incorporated into individual polypeptides decreased in a similar manner for the translation of both HMW RNA and 8 to 12S mRNA. Virion-released 8 to 12S mRNA derived from virion-associated HMW RNA during a chase in the presence of ATP, GTP, and S-adenosylmethionine was also translated. At low RNA concentrations, the derived RNA appeared to stimulate amino acid incorporation more efficiently than the HMW RNA precursor. However, at higher concentrations of this RNA, protein synthesis was severely inhibited.


Membrane fusion as a mechanism of simian virus 40 entry into different cellular compartments. Permissive and nonpermissive simian virus 40 (SV40)-infected cells were ultrastructurally analyzed. Viral particles were found in the cytoplasm, rough endoplasmic reticulum, nuclear envelope, lysosomes, and mitochondria. Upon entering the cell the virion obtains a tight membrane envelope. It seems to be either released from the envelope upon fusion with other membranes of the cell or aggregated into tubular membrane specializations upon fusion with other membrane-enveloped particles. Reconstructed morphological sequences and the finding of SV40 in different spaces of the cell suggest that entry of SV40 into the different compartments and eventually into the site of replication is facilitated by its capacity for being enveloped by a variety of membranes (notably the cell membrane and the nuclear membrane) and the sequential fusion and fission of these membranes.


Comparison of the expression of the src gene of Rous sarcoma virus in vitro and in vivo. We have compared the polypeptide products of the src gene of several strains of Rous sarcoma virus produced by in vitro translation of heat-denatured 70S virion RNA in the nuclease-treated reticulocyte lysate with those present in chick cells transformed by these viruses. We have done this by immunoprecipitation, using sera from rabbits injected at birth with Schmidt-Ruppin Rous sarcoma virus. In vitro translation results in the synthesis of at least nine polypeptides which appear to be encoded by the src gene. These range in size from 17,000 to 60,000 daltons. The sera from tumor-bearing rabbits precipitated these polypeptides arising from the in vitro translation of RNA from Schmidt-Ruppin Rous sarcoma virus of both subgroup A and subgroup D and from one stock of Prague Rous sarcoma virus of subgroup C. In each case, all of this family of related polypeptides could be precipitated except the smallest, the 17,000-dalton polypeptide. No precipitation of analogous polypeptides resulting from the translation of RNA from other strains of Rous sarcoma virus was observed. Cells transformed by these three strains of Rous sarcoma virus contain easily detectable amounts of a polypeptide, p60src, essentially identical to the 60,000-dalton in vitro product. With one exception, they do not contain significant amounts of polypeptides analogous to the smaller in vitro products which can be precipitated by these sera. Cells transformed by one stock of Schmidt-Ruppin Rous sarcoma virus of subgroup A did contain a 39,000-dalton polypeptide, which was related, by peptide mapping, to the 60,000-dalton polypeptide and was similar in size to a precipitable in vitro product. The 60,000-dalton polypeptide present in transformed cells appeared to be phosphorylated 10 to 25 min after its synthesis, metabolically very stable, and not derived from a precursor polypeptide. All immunoprecipitates from transformed cells which contained p60src also contained an 80,000-dalton phosphoprotein. This polypeptide is unrelated to p60src, as determined by peptide mapping, and may well be a host cell polypeptide which is specifically associated with p60src.


Nucleotide sequence relationships between the genomes of an endogenous and an exogenous avian tumor virus. We have used mapping of large T1 oligonucleotides to examine the genome of Rous-associated virus-O (RAV-O), an endogenous virus of chickens, and to compare it with that of Prague strain Rous sarcoma virus, subgroup B, (Pr-RSV-B), an exogenous sarcoma virus. To extend the sensitivity of such comparisons, we have developed a system of nucleic acid hybridization and hybridization-competition combined with fingerprinting. This method allows us to estimate the relative degree of relatedness of various portions of the viral genomes. From the results of this study, we have concluded that the genomes of Pr-RSV-B and RAV-O are related in the following way. The 5'-terminal half of the genomes (corresponding to the gag and pol regions) is virtually identical, with only scattered single nucleotide differences. This region is followed by a region comprising 25 to 30% of the genome (the env region) which contains substantial nucleotide sequence differences, most or all of which are due to single base changes. The env-coding region can be further subdivided into three regions: a more variable region probably containing sequences coding for subgroup specificity, flanked by relatively common sequences on each side. To the 3' side of the env region, the RAV-O genome contains a very short sequence not found in Pr-RSV-B, whereas the Pr-RSV-B genome contains a much longer unrelated sequence. The central portion of this sequence comprises the src gene as defined by transformation-defective mutants. Particularly striking is the absence, in the RAV-O genome, of any nucleotide sequence related to the "c region" found very near the 3' end of all exogenous tumor viruses. Both the Pr-RSV-B and RAV-O genomes contain the identical terminally redundant sequence of 21 nucleotides near each end of the genome.


Characterization of the amino-terminal tryptic peptide of simian virus 40 small-t and large-T antigens. Simian virus 40 small-t and large-T antigen were synthesized in vitro and labeled with methionine donated by initiator tRNA. Tryptic peptide fingerprinting was used to identify the amino-terminal peptide of the two proteins. Similar fingerprint analysis of small-t and large-T made in vitro in the absence of acetyl coenzyme A showed that the mobility of the amino-terminal peptide was changed under these conditions and suggested that it is acetylated. These data establish that the amino-terminal methionine residue of simian virus 40 small-t and large-T results from an initiation event, not post-translational cleavage, and provides additional evidence that the amino terminus of both proteins is acetylated. The identification of the amino-terminal peptide provides a useful marker for further studies on different forms of T-antigen from cells infected with and transformed by simian virus 40 and related viruses.


Structural proteins of equine infectious anemia virus. Equine infectious anemia virus was found to be comprised of fourteen polypeptides of molecular weight ranging from 10,000 to 79,000. Eighty percent of the virion protein was accounted for by five polypeptides, including two non-glycosylated components (p29 and p13) comprising one-half of the virion protein and three glycoproteins (gp77/79, gp64, and gp40).


Retroperitoneal myxoid variant of malignant fibrous histiocytoma: report of a case. A case of a retroperitoneal myxoid variant of malignant fibrous histiocytoma is reported. The chief complaints were remittent fever and a painful mass on the right flank, which were misdiagnosed as acute inflammatory disease.


Urachal signet-ring cell carcinoma, a rare variant of vesical adenocarcinoma: incidence and pathological criteria. Of 715 cases of vesical tumors reviewed 18 adenocarcinomas were selected for further study, 5 of which fulfilled all criteria of urachal origin. Herein is reported 1 rare case of such a carcinoma of the signet-ring cell type and the morphological criteria of this variant are discussed briefly. After undergoing radical cystectomy and ureterosigmoidostomy the patient has been free of recurrent tumor or metastasis for 6 years.


Localization of prolyl hydroxylase by the immunoperoxidase method in cardiovascular tissues of hypertensive rats. An immunohistochemical method and light microscopy were utilized to determine localization of prolyl hydroxylase in the cardiovascular tissues of hypertensive rats. The blood vessels and renal glomerulus from these animals demonstrated an enhanced immunoreaction for prolyl hydroxylase. As the most prominent staining was observed in medial smooth muscle cells of blood vessels, these are probably the major collagen-producing cells in arteriosclerotic lesions induced by hypertension. In the glomerulus, endothelial cells and probably mesangial cells are mainly responsible for the collagen formation. An intense immunoreaction was also found in the fibroblasts which proliferated in the area of myocardial fibrosis in hypertensive rats, while there was no specific staining in myocardial cells in either hypertensive or normotensive rats.


Comparative controlled clinical trial of pivmecillinam and nalidixic acid in patients with acute simple urinary tract infections. We performed a controlled double-blind clinical study with PMPC to investigate its therapeutic usefulness in acute simple cystitis in comparison with NA, with the results as follows: 1. In both treatment groups, PMPC proved to be remarkably more active (MIC) than NA against the bacterial isolates tested in vitro. 2. PMPC, administered in dosis (200 mg per day) one-tenth those of NA (2,000 mg per day), produced a greater improvement (therapeutic effects) than NA. 3. Side-effects were apparently less frequent with PMPC, as compared to NA. The results indicate a remarkable usefulness of PMPC in the treatment of acute simple cystitis.


The effect of thyroxine on (Na+, K+)-ATPase from the heart and the kidney of rabbit. The effect of thyroxine on membrane bound (Na+, K+)-ATPase isolated as a microsomal fraction from rabbit heart and kidney was investigated. In the heart, thyroxine administration produced an increased Ki value (a concentration of ouabain required for half maximal inhibition of (Na+, K+)-ATPase activity) without alteration of the specific activity of cardiac (Na+, K+)-ATPase, indicating that the digitalis sensitivity of cardiac (Na+, K+)-ATPase was decreased. On the contrary, a significant increase of the specific activity of renal (Na+, K+)-ATPase was observed without change in its digitalis sensitivity. These results suggest that (1) a decreased sensitivity of cardiac (Na+, K+)-ATPase to digitalis glycosides in thyrotoxic animals may contribute to the decrease in the inotropic and toxic effects of the digitalis glycosides in the hyperthyroid state, and that (2) there may be an organ difference in (Na+, K+)-ATPase.


Epidemiological studies on Japanese encephalitis in Kyoto City area, Japan. III. Seasonal prevalence of virus infections in several pig populations shown by virus recovery from engorged Culex tritaeniorhynchus summorosus. When vector mosquitoes engorged by feeding on pigs are tested for virus recovery after incubation for 7 to 10 days, the results may show mosquito infection itself. Therefore, seasonal prevalence of infection in each pig population can be estimated from course of the infection rate among mosquitoes. Many mosquitoes of the main vector of Japanese encephalitis virus, Culex tritaeniorhynchus summorosus, collected by light traps everyday or every other day in some pig sheds from 1967 to 1970 were tested for virus recovery after incubation. The tests were positive during about a month period each summer, and the peak infection rate was high being over 10%. The course of the mosquito infection showed a certain pattern with one or two peaks between the initial recovery and the highest peak. From the interval of 12 to 13 days after the first recovery to the peak, cyclic infection between the pig and the mosquito may occur at the same interval.


Effect of dimercaptosuccinic acid on toxicity of Habu snake (Trimeresurus flavoviridis, Hallowell) venom. Habu venom (HV) incubated with dimercaptosuccinic acid (DMS) or thiosuccinic acid (TMA), was given subcutaneously to mice. The LD50 of HV was 19.7 mg/kg, and after treatment with TMA and DMS, it was 38.1 and 47.1 mg/kg, respectively. The logarithm concentration--mortality curve for the DMS-treated HV shifted to the right compared with the curve for crude HV. The curve for the TMA-treated HV was intermediate between these two. Decimal two mg of HV was then incubated with DMS, and such was given intramuscularly to mice. Hemorrhage and edema which occurred after administration of crude HV were markedly decreased with injection of DMS-treated HV, but the myonecrosis was not greatly affected. At 24 hr after the intramuscular dosing of 1 mg of HV into rats, lymphopenia, acute involution of lymphatic tissue, decrease in liver glycogen and lipid granules in zona fasiculata were apparent, indicating the mark of a stressor. When the DMS-treated venom was administered, the blood picture and histological findings did not differ greatly from the controls. As DMS has marked anti-HV activity, it may be used to investigate treatments for cases of Habu snake bite.


Influences of verapamil, X-537A, A-23187 and adenosine 3',5'-cyclic monophosphate on release of 5-hydroxytryptamine from rat brain slices. Influences of verapamil, X-537A, A-23187 and cyclic-AMP on the release of [3H]-5-HT taken up into rat brain slices, were examined. Incubation with 40 mM KCl induced tritium release which was dependent on the presence of Ca2+. Verapamil, which blocks Ca2+ influx in excitable tissues, decreased potassium-induced release of 5-HT. Tritium release induced by ionophore X-537A was not dependent on extracellular Ca2+ while that induced by A-23187 required Ca2+. Cyclic-AMP, dibutyryl cyclic-AMP and theophylline did not significantly stimulate 5-HT release either in the presence or absence of Ca2+.


[Triglyceride, total cholesterol and lipoprotein fraction cholesterol levels in the blood plasma of elderly and long-lived persons in the Abkhazian SSSR]. The results of examination of 21 males and 30 females of the category of elderly and long-lived persons (81--106 years old) indicate the low content in the blood plasma of total cholesterol (173 mg/100 ml), beta-lipoprotein cholesterol (106 mg/100 ml), pre-beta-lipoprotein cholesterol (18 mg/100 ml), and triglycerides (91 mg/100 ml). The average content of these lipid complexes was lower in males than in females. The low concentration of beta- and pre-beta-lipoprotein cholesterol and the large portion of alpha-lipoprotein cholesterol content in relation to the content of total cholesterol in blood plasma are evidence of a favourable proportion of atherogenous and non-atherogenous classes of lipoproteins in blood plasma of elderly and long-lived persons, which is evidently one of the causes of the lower incidence of ischemic heart disease among them and their high longevity.


Growth assessment in abnormal children.

Growth assessment in abnormal children. Growth assessments are made in children to monitor their growth with time. In children with chronic disease, these data aid in determining the effect of disease on growth and planning and evaluating therapy. Stature is the most important aspect of physical growth, but weight, body composition, skeletal maturation, and sexual development are also important. Methods for making these assessments are given. Techniques for data reduction and statistical treatment of data comparing groups of children are discussed.


[Aesthesiophysiological and neurophysiological principles of organisation of the visual system (author's transl)]. The neuronal flow of signals of the visual system and the cortical modulous characteristic are described. Possible and not yet possible correlations between neuronal activity and aesthesiophysiological experience, as well as the cortical visual projection chain and its plasticity, are discussed.


[Mucoepidermoid carcinoma of the conjunctiva (author's transl)]. This is a report on a mucoepidermoid carcinoma in a 69 year old male, a rare occurence, originating clinically from the conjunctiva of the globe. The microscopic features, the pathogenesis and the histological differentiation are discussed.


[Rotavirus infections in children (author's transl)]. In 43 out of 90 children suffering from acute gastroenteritis Rotaviruses could be identified in stool-specimens by electronmicroscopy. Symptoms were watery diarrhoea (100%), vomiting (88%), fever (77%), dehydration (47%) and upper respiratory tract infection (21%). In 3 out of 9 patients liver involvement could be documented. In 29 children i.v.-fluid therapy for 1-2 days was necessary. Only in 1 patient severe diarrhoea persisted for 11 days.


[Connections between respiratory regulation and paradoxical sleep in a patient with Joubert's syndrome (author's transl)]. This study reports on eight patients whose cases have been described in literature, and two patients treated by the author, showing the typical signs of Joubert's syndrome. This disease pattern is characterised by episodic hyperpnoeas and apnoeas, retardation, muscular hypotension, opsoclonia, complete or partial agenesis of the vermiform process of cerebellum, as well as a dilated fourth ventricle. The clinical symptoms are compared with the characteristic signs of REM sleep and of cataplexy.


Mineralocorticoids, salt balance and blood pressure after prolonged ACTH administration in juvenile hypertension. The effect of a 5 day ACTH test (40 U/24 h) on plasma aldosterone (aldo), deoxycorticosterone (DOC), plasma renin activity (PRA) and urinary excretion of aldosterone-pH1-conjugate (pH-1-aldo) and tetrahydro-DOC (TH-DOC) was investigated in 8 normotensive children (group I), 8 patients with hypertension of unknown origin (group II), and 4 hypertensive children with dexamethasone suppressible hyperaldosteronism (DSH) (group III). Changes in blood pressure and sodium balance were studied in all groups. Under baseline conditions there was no hormonal difference between group I and II. In contrast, the children in group III had a suppressed PRA and a 1.5--2 fold elevation of aldo and DOC. Plasma DOC and urinary THDOC increased continuously 10--50 fold in all groups during the ACTH test. Aldo rose transiently 2--4 fold on the first day of ACTH and fell subsequently below baseline levels in group I and II. The children with DSH (group III), however, showed an unusual, sustained aldo stimulation with ACTH. PRA decreased significantly after ACTH in group I and II. Sodium retention aTH administration. The highest blood pressure rise was observed in group III (from 124/72 to 139/90 mm Hg). The blood pressure response to ACTH was partly sodium dependent. Although aldo and DOC and sodium retention may contribute to the ACTH induced blood pressure elevation, other factors must play a role.


The effect of chronic ACTH treatment on blood pressure and urinary excretion of steroids in the rat. The effects of subcutaneous injections of synthetic ACTH during 14 subsequent days has been studied in the rat. ACTH caused a loss in body weight which was related to a negative water balance. Blood pressure rose rapidly and reached values higher than 180 mm Hg in all rats after 10 days of ACTH administration. During this period, urinary excretion of corticosterone and 18-hydroxy-deoxycorticosterone (18-OH-DOC) was increased more than ten times, while aldosterone excretion was increased only during the first two days. After withdrawal of ACTH, excretion of steroids normalized, or in some cases was even suppressed and water balance and body weight gain returned to normal values. However, blood pressure remained slightly higher than in controls after ten days. The effects of ACTH on water balance and blood pressure resemble those of corticosterone in the rat. The rapidly induced and sustained changes in blood pressure by ACTH administration suggest that this may be an useful model of experimental hypertension.


Inhibition of the renin-angiotensin-system in Brattleboro rats with hereditary hypothalamic diabetes insipidus. Brattleboro rats homozygous for hypothalamic hereditary diabetes insipidus (DI rats) were used to investigate the following questions: a) Do exogenous and endogenous angiotensin II (AII) have an antidiuretic effect in diabetes insipidus? b) Does AII mediate the antidiuresis induced by furosemide? The following results were obtained: 1. AII (5 mg/kg s.c. in oil) and furosemide (50 mg/kg i.p.) decreased urine flow and increased urinary sodium excretion. Furosemide led to a two-fold increase of AII plasma concentrations and a decrease of plasma sodium levels. 2. SQ 14 225 (2 x 2.5 mg/kg p.o.), an angiotensin I-converting enzyme inhibitor, led to an increase of urine flow and to a slightly elevated urinary sodium excretion. 3. When the formation of AII was blocked by SQ 14 225 (2 x 2.5 mg/kg p.o.), AII plasma concentrations were 2.5-fold decreased, but furosemide still reduced urine flow. We conclude that plasma AII might have an antidiuretic action in DI rats. However, AII does not mediate the antidiuresis induced by furosemide.


Influence of clofibrate on blood viscosity in primary hyperlipoproteinemia. In patients with primary hyperlipoproteinemia (23 patients type II a and II b, 13 patients type IV), changes in lipoprotein concentrations (lipid fraction), fibrinogen concentrations, in kinematic serum and plasma viscosity (determined by means of a capillary viscosimeter) and changes in relative apparent viscosity at shear rate 46 s-1 and 115 s-1 (determined by means of a plate-cone-viscosimeter) were measured before and after a clofibrate therapy (2 X 1 g/day) lasting for 7 to 9 weeks. Serum and plasma viscosity was lowered significantly in both types II and IV. The apparent viscosity decreased at shear rate 46 s-1 in type IV, whereas it remained unchanged in type II. Moreover, there exists a qualitative correlation between changes in serum viscosity and changes in lipoprotein concentration. Fibrinogen concentration remained unaltered.


Collagen turnover and the growth state in 3T6 fibroblast cultures. The metabolic turnover of collagen in 3T6 fibroblast cultures was studied at various stages of growth by compartmental analysis of hydroxyproline content and of the conversion of radioactive proline to hydroxyproline. Quantitative and radioactive hydroxyproline measurements were directly parallel, although the latter method was more sensitive in demonstrating collagen synthesis in all phases of growth. Hydroxyproline formation as an index of collagen synthesis was abruptly accelerated at the time of confluence, and was well maintained at the new rate despite a gradual decline in the rate of general protein synthesis. Ethanol fractionation of growth medium proved superior to perchloric acid extraction in providing a pool of soluble hydroxyproline clearly derived from collagen degradation. Breakdown products were released at a constant rate per cell in all growth phases and accumulated to high levels in continuous culture. The fractional rate of collagen breakdown (percentage of hydroxyproline radioactivity) was highest in early logarithmic growth. Its gradual decline as cultures aged reflected the increased hydroxyproline content and improved stability of collagen under these conditions.


Cell surface glycosyltransferases--do they exist? The presence of glycosyltransferases on surfaces of mammalian cells has been reported by many investigators and a biological role for these enzymes in cell adhesion and cell recognition has been postulated. Critical analysis, however, showed 2 major complications regarding the assay for cell surface glycosyltransferases: 1) hydrolysis of the nucleotide sugar by cell surface enzymes and subsequent intracellular use of the free sugar and 2) loss of cell integrity if trypsinized or EDTA-treated cells were used in suspension assays. We have assayed intact, viable cells in monolayer for cell surface glycosyltransferases using conditions under which intracellular utilization of free sugars generated by hydrolysis of the nucleotide sugar was prevented. Our data demonstrate that the presence of galactosyltransferases on the surface of a variety of cells, including established (normal and virally transformed) as well as nonestablished cells, is unlikely. No evidence for the existence of cell surface fucosyl- and sialytransferases could be obtained, but our data do not exclude the possibility that low levels of these enzymes are present.


Gycoprotein and protein precursors to plasma membranes in vesicular stomatitis virus infected HeLa cells. Vesicular stomatitis virus is known to mature at HeLa cell plasma membranes. To study the process, cells, infected with vesicular stomatitis virus, were fractionated after short term labeling studies (1 min pulse, 1 min chase) to determine the assembly kinetics of G protein and M protein into plasma membranes. Newly synthesized M protein was found released in the supernatant from which free polysomes were sedimented during sucrose gradient analysis of these polysomes. If this M protein is particle bound, it must have a density of less than 1.08 g/ml. About 40% of this M protein so labeled was not sedimentable at 165,000 X g for 16 h. This newly synthesized M protein had not yet assembled into plasma membrane and thus must represent an internal pool. This and previous studies show that it has a subsequent transit time to the plasma membrane of about 2 min. Once associated with plasma membranes, M protein decayed in an approximately logarithmic fashion indicating that newly synthesized M randomly mixes (and turns over) with preexisting M protein. G protein was particle bound in a 1 min pulse, 1 min chase, and was never found released in a soluble form. At the later time when fucose is added to G protein, the oligosaccharide moiety is near to complete, and on completion is about 2,000 in molecular weight. Evidence is presented showing that fucose is probably attached to the N-acetylglucosamine of the protein carbohydrate linkage. G protein to which fucose had just been added was located internally on a membranous fraction of density 1.14 g/ml in sucrose; its subsequent transit time from this pool (which in uninfected cells is between 1--2% of the total cell fucosyl glycoprotein) was about 15 min. Because their densities were different and their transit times were different, internal newly synthesized M and fucosyl G protein which assemble into plasma membranes were not on the same internal membranous component. Association of M protein with the plasma membranes may thus occur from a nonsedimentable soluble cytoplasmic pool by a process of direct adsorption.


Erythrocyte membrane alterations in Huntington disease: effects of gamma-aminobutyric acid. The interaction of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) with erythrocyte membranes from patients with Huntington disease and normal controls has been studied by electron spin resonance. GABA affects the physical state of erythrocyte membrane proteins in control and Huntington disease differently. In addition, after exposure of spin-labeled Huntington disease erythrocyte membranes to 0.1 mM GABA, the relevant electron spin resonance parameters reflecting the physical state of membrane proteins are indistinguishable from those of untreated control membranes. These findings support the concept that this disease is associated with a generalized membrane defect.


Use of photoaffinity nucleotide analogs to determine the mechanism of ATP regulation of a membrane-bound, cAMP-activated protein kinase. Using a radioactively tagged, photoaffinity analog of cAMP, 8-azidoadenosine-3',5'-cyclic monophosphate (8-N3 cAMP) and [gamma32P]ATP, the membrane-binding properties of both the regulatory and catalytic subunits of the cAMP-activated protein kinase of human erythrocyte membranes were investigated. [32P]8-N3 cAMP was used to locate and quantify regulatory subunits. Increased phosphorylation of specific membrane proteins by [gamma32P]ATP was used to determine the presence of the catalytic subunit. The data support a mechanism which operates through a tight membrane-bound regulatory subunit and a catalytic subunit that is released from the membrane when cAMP is present and the Mg.ATP concentration is below approximately 10 micrometer. The catalytic subunit is not required for the Mg.ATP inhibition of 8-N3 cAMP binding. Experiments with a photoaffinity analog of ATP, 8-azidoadenosine triphosphate (8-N3ATP), support the hypothesis that ATP hydrolysis and phosphorylation are not involved in the regulation. The data indicate that the regulatory subunit contains an ATP regulatory site which inhibits 8-N3 cAMP binding and the release of the catalytic subunit. These results indicate that the membrane-bound type I enzyme (type IM) differs significantly from the soluble (type IS) enzyme studied on other tissues. These enzymes are compartmentalized by being in different cellular locations and are regulated differently by Mg.ATP.


Glucocorticoid-mediated alteration in growth factor binding and action: analysis of the binding change. The addition of the glucocorticoid analog dexamethasone (DX) to serum-free cultures of human fibroblasts caused a twofold enhancement of the mitogenic response to epidermal growth factor (EGF), although DX by itself was not mitogenic. A basis for this effect was suggested by studies showing that DX also increased the cellular binding of 125I-EGF. DX increased the ability of the cells to bind 125I-EGF only at low physiological concentrations of this polypeptide. Thus, data from 125 I-EGF binding to cells incubated without DX produced a linear Scatchard plot, whereas the data from 125I-EGF binding to DX-treated cells led to an upwardly curvilinear Scatchard plot. Measurements of 125I-EGF association with the cell surface and cytoplasm indicated that this binding change involved an alteration of cell surface EGF receptors. The binding change appeared not to involve negatively cooperative interactions between EGF receptors, nor a change in the number of receptors. The binding alteration could be explained by a model in which DX converted 25--30% of the cell surface EGF receptors to a form having a fourfold increased affinity.


REM sleep time and digit span impairment in alcoholics. In a group of 20 abstinent alcoholics, the amount of REM sleep was correlated with the degree of Digit Span scatter from the modified verbal mean of the WAIS. The Digits Backward component was more strongly related to REM time than was the Digits Forward component, suggesting an association between reduced REM sleep time and short-term memory impairment.


The relationship of wives' treatment to the drinking status of alcoholics. When an alcoholic's wife is active in Al-Anon, participates in her husband's inpatient treatment or postreatment counseling or receives several types of treatment, her husband is more likely to be abstinent.


Breast carcinoma associated with Klinefelter syndrome: a case report. Klinefelter syndrome increases the risk of developing breast cancer to approximately 1/5 that of women and 20 times that of normal men. A case report and the patient's response to hormone manipulation for metastatic disease is described.


Malignant fibrous histiocytoma: report of five cases and a review of the literature. Five cases of malignant fibrous histiocytoma are presented and the relevant literature is reviewed. All the patients had locally extensive tumor or eventual recurrent or metastatic disease. Determining malignancy by histologic criteria is difficult. Therefore, histologic, gross, and clinical behavior of the tumor is important. Though the role of radiation therapy and chemotherapy is not yet established, it appears that at least wide "cancer resection," if possible, is the treatment of choice. The unusually high incidence of nonresectable, recurrent, or metastatic disease in retroperitoneal histiocytomas raises the question as to whether all three modalities of therapy should be used in the treatment of tumors at this particular site.


Epstein-Barr virus (EBV) antibody in patients treated by radical radiotherapy for head and neck cancer. Antibody against Epstein Barr Viral capsid (EBV-VCA) was measured in 65 patients with primary head and neck cancer referred for radical radiotherapy. Sixty-three percent had locally advanced cancer and 37% had early disease. Forty-eight percent had detectable antibody in their sera. Thirty-three percent had elevated titers (above 1:20 dilution). Only 19% of cases with early cancer had increased titers. Almost 50% of those with locally advanced cancer or recurrence following treatment had titers above 1:20. A rise in titer within six months following radiotherapy was associated with a significant incidence of recurrence. There was no correlation between delayed hypersensitivity skin reaction to 2--4 dinitrochlorobenzene (DNCB) and titer values. EBV-VCA may be an additional parameter which can be used to determine host defenses in patients with malignancies.


Pancreas cancer -- duct cell adenocarcinoma: survival in relation to site, size, stage and type of therapy. The records of 508 patients with cancer of the pancreas admitted to Memorial Hospital in New York from 1949 through 1972 were examined. Ten distinctive morphological types were delineated and the pathological features and response to various modes of therapy of the most common type -- duct adenocarcinoma -- were studied in 380 patients. Median survival was related to: the site of the cancer -- it was longer with tumors of the head than those of the body or tail; the size of the tumor -- cancers smaller than 3 cm were associated with over twice the survival of those with large tumors; the stage -- stage I patients had over twice the survival of those of stages II and III; and the type of therapy employed. Actuarial survival rate at one year was: with no specific therapy, 0%; with chemotherapy, 1%; after palliative by-pass surgery, 3%; following radiation therapy, 9%; and after all types of "surative" surgery, 21%. The only survivors at five years were in the "curative" surgery group, but these represented only 1% of all patients. Revolutionary changes in diagnosis and therapy will have to occur if significant increase in survival rate is to be achieved.


Sequential and adjuvant chemotherapy for malignant astrocytoma of the brain. Twenty-nine patients with grade III or IV astrocytomas were treated with 1,3 bis(2-chloroethyl)-1-nitrosourea (BCNU), 75--100 mg/M2 intravenously (IV) for two consecutive days every four to six weeks, in an effort to improve the quality and length of their survival following surgical resection. Twenty-one of these patients received adjunctive chemotherapy as soon as they recovered from surgery and 18 received concomitant adjunctive radiation therapy as well. Eight patients were treated with radiation therapy after surgery, and BCNU was not added until evidence of tumor growth appeared. BCNU was discontinued and the epipodophyllotoxin, VM-26, was given at a dose of 100 mg/M2 IV weekly when further tumor growth occurred. Patients receiving adjuvant chemotherapy had a shorter mean and median survival than patients receiving BCNU when progression appeared following radiation therapy. Six patients with progressive disease following surgical resection and radiation therapy for grade II astrocytoma were treated with BCNU. Improvement or stabilization of neurologic symptoms occurred in four of these patients. This trial of lower-dose BCNU therapy produced survival rates similar to higher-dose studies and permitted fewer physician visits by the patient.


Small cell undifferentiated bronchogenic carcinoma: current status with emphasis upon the role of chemotherapy. Current opinions concerning tumor biology and clinical characteristics of small cell undifferentiated bronchogenic carcinoma are reviewed. Special emphasis is placed upon chemotherapy for this lung cancer subtype and presently achievable response rates and survival times are presented. A series of 16 patients with small cell undifferentiated bronchogenic carcinoma is also presented. All patients were given cyclophosphamide, methotrexate, vincristine, and procarbazine as treatment for this neoplasm. Sixty-eight percent of patients responded and the survival time in partial responders was 33.4+ weeks as compared to 13.7 weeks with nonresponders. These data correlate well with the previous data of Alberto et al [Alberto P, Brunner KW, Martz G, Obrect JP: Cancer 38:2208--2216, 1976], who investigated the same agents for this tumor, but at higher dosages.


Pericardial reconstruction of the membranous trachea after resection of adenoid cystic carcinoma (cylindroma). An intraluminal adenoid cystic carcinoma (cylindroma) in the patient reported herein involved just the membranous portion of the distal region of the trachea and extended caudally to include the carina and the membranous portions of both main-stem bronchi--a total linear involvement of 6 cm. The tumor occluded 90% of the airway in its greatest extension. Conservative resection of this extensive tumor was successfully performed by membranous tracheal reconstruction with a pedicled autogenous pericardial patch graft.


Congenital absence of the portal vein.

Congenital absence of the portal vein. A 4 1/2-year-old girl is described in whom the portal vein is absent and the venous return from the gastrointestinal tract, spleen, and pancreas is through the left renal vein into the inferior vena cava. She had a hepatoblastoma, which was treated surgically by right hepatic lobectomy. Regeneration occurred in the remaining left lobe within 3 months after surgery. This is the second such case documented in the literature.


Anomalous vitamin E effects in mitochondrial oxidative metabolism. Three different vitamin E effects, suggestive of specific antioxidant effects, were discovered in the protective action of vitamin E against respiratory decline (a decrease in mitochondrial respiration attributed to a "leakage" of electron transport radicals). No correlation was found between respiraotry decline and random lipid peroxidation. The mechanisms behind two of the three atypical vitamin E effects were defined. Both involve an artifact in the TBA assay for lipid peroxidation. This artifact occurs when TBA assays are carried out in the presence of sucrose and acetaldehyde; the latter is produced from ethanol, the solvent used to add vitamin E to preparations. The artifact in the TBA assay for peroxidations appears also to be responsible for differing interpretations of the hepatotoxic effect of ethanol.


The hormonal induction of maturation in amphibian oocytes. The maturation of the amphibian oocyte has been analyzed. Progesterone as well as organomercurials, lanthanum chloride and propranolol rapidly induce maturation. These chemicals are active only is applied on the cell surface. The mechanism seems to be an induction of the migration of Ca2+ from the cell membrane to the cytoplasm. K + may also play a role. Progesterone induced maturation involves synthesis of histone and histone kinase as well as several biologically active but chemically unidentified factors. cAMP does not seem to be directly involved, whereas protein phosphorylation is so.


Factors associated with utilization of the swine flu vaccination program among senior citizens in Tompkins County. The health belief model is tested in the context of the swine flu vaccination program for senior citizens. Analysis is based on 232 responses to a questionnaire mailed to a simple random sample of 500 senior citizens in Tompkins County, New York. Social and psychologic variables identified by the model as important in determining utilization of preventive health services are: perceived susceptibility and severity of disease, perceived efficacy and danger associated with the preventive action, and general health motivations. Differences of means between users and nonusers for these variables are computed and compared with the results of a more sophisticated analytic technique--logit analysis--for use with dichotomous dependent variables. Results reveal that the health belief model accounts for 34 per cent of the variance in use of the vaccine by senior citizens. Perceived susceptibility to the disease and amount of danger associated with receiving the swine flu immunization are found to be the most important determinants of utilization.


Administrative costs of the influenza control program of 1976--1977 in Illinois. In 1976, many resources of state and local agencies were devoted to planning, organizing, implementing and evaluating the influenza immunization program. The costs included salaries and other expenses of specifically employed personnel; diversion of the time of others from their usual responsibilities; and donated resources. They were assessed retrospectively and reported by responsible local agency personnel on a questionnaire. Costs of donated services and other resources were estimated based on assigned unit value. The total cost of the program in Illinois was $3.334 per dose of which $1.733 was accounted for by local agencies, $0.075 by the state agency, and $1.526 by the federal government, including the cost of vaccine doses remaining unused. If the program could have been carried through to include the intended larger numbers of persons, both the administrative costs and the vaccine costs per dose administered would have been much less. The financial cost of the campaign exceeded the federal grant. It must be weighed against the administrative benefits including improved ability to conduct large scale preventive programs and awareness of the importance of both risks of benefits of immunization.


[Surgery of congenital angiodysplasia (author's transl)]. Diagnostically and therapeutically, three types of angiodysplasias interfere with venous surgery: 1. Congenital arteriovenous fistulas (Type F.P. Weber: secondary varicosis with local gigantism)--surgical reduction of the shunt-volume is usually indicated. 2. Type Klippel-Trenaunay: Surgery for varicose veins is dangerous due to the frequent hypo- or aplasia of the deep venous system. 3. Venous hemangiomatosis (Type Servelle-Martorell or Kasabach-Merritt): Any surgical intervention is contraindicated (only external compressive therapy).


[Lung-cancer (author's transl)].

[Lung-cancer (author's transl)]. The prognosis after resection of bronchial carcinoma is not only influenced by operative techniques but by the histologic cell type, the general conditions of the patient, and specially by the stage of the disease. Therefore I recommend the routine use of mediastinoscopy, since resection of the tumor proves to be not curative in presence of perinodal growth or contralateral lymph node metastases. Followup of all patients is necessary for critical evaluation of surgical success and quality of live.


[Therapy of primary oat-cell carcinoma of the larynx (author's transl)]. The case of primary oat-cell carcinom of the larynx with metastases in the thyreoid gland and paratracheal lymphnodes is reported on. The different methods of treatment are examined, used examples of the much more common oat-cell carcinoma of the lung. The applicability of the methods to oat-cell carcinoma of the larynx is discussed. Our treatment scheme of surgery and extended radiation is used if the tumor is known to be locally restricted.


Fibrous histiocytoma of the head and neck: A case report. Fibrous histiocytomas are soft tissue tumors of histiocytic origin. One percent prove to be malignant. Reliable histologic criteria of malignancy are few, if any, and the diagnosis of malignancy often must be made on clinical (metastases) rather than histologic grounds. Thirty-five cases originating in various deep structures of the head and neck, excluding the orbit, have been reported in the literature since 1972. One additional case, a malignant tumor of the submandibular gland, is added herewith. Recurrence following initial surgery has been common and stems from inadequate excision of the primary lesion. Microscopic spread of this tumor from its primary site calls for radical rather than conservative surgical excision. At present, radiotherapy and chemotherapy appear to be of little value in the treatment of these tumors.


Low density lipoprotein metabolism in type IV and type V hyperlipoproteinemia. Low density lipoproteins (LDL) are thought to arise largely from degradation of triglyceride-rich very-low-density lipoproteins (VLDL). LDL kinetics in patients with Type IV and Type V hyperlipoproteinmia were studied and compared with normal subjects. LDL labeled in the protein moiety with 125I was used as a tracer. There was no significant difference in LDL turnover between the three groups, suggesting that a catabolic defect in VLDL degradation to LDL may exist in both Type IV and Type V hyperlipoproteinemia.


Studies on the pathogenicity of human-origin parainfluenza virus in the brain of mice. The pathogenicity of parainfluenza type 2 (croup-associated) virus known to cause infections of the respiratory tract in the early life of man was studied in the brain of mice. One- to 4-day-old sucklings and 4-week-old mice were inoculated intracerebrally with the virus. The virus multiplied in sucklings, but not in adults. Most mice inoculated intracerebrally with the virus appeared healthy. Histological examination showed minimum inflammatory changes, although moderate hydrocephalus developed in three of twenty-one sucklings by 6 weeks post-infection. Immunofluorescent study in sucklings showed viral antigens in ependymal lining cells and choroid plexus epithelium during the first two weeks, and parenchymal cells for more than two months. Virus specific antibody response was observed in adults, but not in sucklings. One interesting finding was that viral antigens persisted in six out of 11 suckling brains for one to two months.


Modification of immune response in nude mice infected with mouse hepatitis virus. In nude mice experimentally infected with mouse hepatitis virus (MHV), the numbers of early and later plaque forming cells (PFC) to sheep red blood cells (SRBC) generated in the spleen were 7 to 20 times and 2 to 163 times, respectively, greater than those in non-infected nude mice, when SRBC were given at day 0 to day 21 postinfection. Splenic theta-positive lymphocytes in infected nude mice were shown to increase only at day 10 or more postinfection. PFC response to bacterial lipopolysaccharide, a T cell-independent antigen, was not modified in MHV-infected nude mice.


Liver tumours associated with oral contraceptives. Five young women have been encountered with unusual forms of hepatic neoplasms in a ten year period. Each had been taking an oral contraceptive. Two of the four women with benign lesions noted the presence of their tumours, and another woman presented with abdominal pain. Each of these tumours was resected successfully. The fourth patient had the diagnosis made at laparotomy following the development of haemoperitoneum after an attempt at percutaneous liver biopsy. A fifth patient developed jaundice and investigation revealed a hepatocellular carcinoma which was invading the biliary tree. This experience illustrates the need for periodic physical examination of young women who are taking oral contraceptives.


Liver cell adenoma associated with oral contraceptive hormone therapy. A patient receiving oral contraceptive hormone therapy developed a hepatic adenoma. Widespread haemorrhages, which were apparently unrelated to trauma, developed in the adenoma. Attention is drawn to the increasing incidence of Pill-associated hepatic tumours, and to the possibility of a fatal haemorrhage.


Fatal adenovirus type 7 pneumonia in an adult. A case of fatal pneumonia caused by adenovirus type 7 in an adult is reported. This virus was isolated from the lung tissue, and typical inclusion bodies were found in histological sections. Death due to adenovirus pneumonia in adults appears to be extremely rare.


[Glomus tumors (author's transl)].

[Glomus tumors (author's transl)]. Pathology and clinical picture of glomus tumors are described with emphasis on their location on hand and digits. It is stressed that the knowledge of this rare but extremely painful condition is essential for early treatment. Surgical treatment is standardized and simple.


Recombinational repair of alkylation lesions in phage T4. II. Ethyl methanesulfonate. Treatment of bacteriophage T4 by ethyl methanesulfonate (EMS) caused more than a doubling in recombination between two rII markers. The functions of genes 47, 46, 32, 30, uvsX and y are known to be required for genetic recombination, and mutants defective in these genes were found to be more sensitive to inactivation by EMS than wild-type phage. This suggests that a recombinational pathway involving the products of these genes may be employed in repairing EMS induced lethal lesions. Genes 45 and denV are apparently not involved in recombination, and mutants defective in these genes were not EMS-sensitive. Gene 47, 46 and y mutants which were defective in the repair of EMS induced lethal lesions had no detectable deficiency in their ability to undergo EMS-induced mutation. This implies that recombinational repair of EMS lesions does not contribute substantially to EMS mutagenesis. The results obtained here with EMS are general similar to the results reported in the preceding paper with MNNG, suggesting that the lesions caused by both of these monofunctional alkylating agents may be eliminated by similar recombinational repair processes.


Carbohydrate composition of purified serum glycoproteins in mucolipidosis II and mucolipidosis III. Mucolipidosis II (I-cell disease) and Mucolipidosis III (ML III) are inherited disorders in which the molecular defect may involve an abnormality in a common post-translational modification step (possibly glycosylation) shared by lysosomal hydrolases. We tested whether such an alteration might be a generalized defect in glycoprotein biosynthesis and, thus, be reflected in an abnormal carbohydrate composition of non-lysosomal glycoproteins. The apoprotein of low density lipoprotein (apo-LDL) and immunoglobulin G (IgG) were purified to apparent homogeneity. Gas liquid chromatographic (glc) analysis of the carbohydrate content of these glycoproteins from ML II, ML III and normal sera revealed no differences in the relative ratios and total amounts of mannose, galactose, N-acetylglucosamine and sialic acid. These results suggest that if the postulated post-translational defect in these disorders involves changes in carbohydrate composition, it is not a general defect in glycosylation and may be specific for lysosomal hydrolases.


Partial purification and characterization of cyclic nucleotide phosphodiesterases from human bronchial tissue. DEAE-Sephadex chromatography reveals the presence in extracts of human bronchial tissue of at least three separate cyclic nucleotide phosphodiesterases: a cyclic GMP-specific high affinity enzyme, a non-specific low affinity enzyme, and a high affinity cyclic AMP-specific enzyme. The activity of each fraction was partially characterized with respect to kinetic parameters, thermal stability, and the influence of a number of inhibitors. Each activity was found to resemble the activity of the previously characterized corresponding enzyme from whole lung tissue extracts. A high affinity non-specific phospho-diesterase previously isolated from lung tissue is missing in extracts of bronchial tissue.


[Neurofibromatosis Recklinghausen with cerebral manifestation and deficiency of pituitary hormones (author's transl)]. In a 6 year old boy a spongioblastoma of the optic chiasm was the first manifestation of a neurofibromatosis Recklinghausen. Further characteristic symptoms developed in the following years. This central type of neurofibromatosis was combined with a decreased reserve of the hypophyseal hormones ACTH, growth hormone and FSH.


Apurinic and/or apyrimidinic endonuclease activity in ataxia telangiectasia cell extracts. The possibility that the increased sensitivity of ataxia telangiectasia towards ionizing radiation is related to a DNA-repair deficiency has been examined further. When compared to unaffected controls, 6 lines of fibroblast cells derived from ataxia patients demonstrated a slightly reduced endonucleolytic activity (165 +/- 12 units vs. 214 +/- 28 units) towards apurinic and/or apyrimidinic sites as determined in a "nicking" assay.


Ethylation of DNA and protamine by ethyl methanesulfonate in the germ cells of male mice and the relevancy of these molecular targets to the induction of dominant lethals. The molecular dosimetry of ethyl methanesulfonate (EMS) in the germ cells of male mice has been investigated. The mice were injected i.p. with 200 mg/kg of [3H]EMS and the ethylations per sperm head, per deoxynucleotide, and per unit of protamine were then determined over a 2-week period. The ethylations per sperm head closely paralleled the dominant-lethal frequency curve for EMS, reaching a maximum of 5 to 6.5 million ethylations per vas sperm head at 8 to 10 days after treatment. Ethylation of sperm DNA was greatest at 4 h after treatment, with 5.7 ethylations/10(5) deoxynucleotides, and gradually decreased to 2.2 ethylations/10(5) deoxynucleotides at 15 days after treatment. The ethylation of sperm DNA did not increase in the germ-cell stages most sensitive to EMS, and was not correlated with the dominant-lethal frequency curve for EMS. However, ethylation of sperm protamine did increase in the germ-cell stages most sensitive to EMS, and showed an excellent correlation with the incidence of dominant lethals produced by EMS in the germ cells. A model is presented to explain, at a molecular level, how dominant lethals may be induced in mouse germ cells by EMS. Ethylation of cysteine sulfhydryl groups contained in mouse-sperm protamine could block normal disulfide-bond formation, preventing proper chromatin condensation in the sperm nucleus. Stresses in the chromatin structure could then eventually lead to chromosome breakage, with resultant dominant lethality.


Treatment of Cushing's disease by O,p'DDD. Survey of 62 cases. In a study of nonsurgical therapy of Cushing's disease, 62 patients received O,p'-dichlorodiphenyldichloroethane (O,p'DDD), 16 of whom also received cobalt irradiation of the pituitary. After an initial treatment period averaging eight months, a remission of the disease was obtained in 38 of the 46 patients given O,p'DDD alone and in all patients who received drug combined with radiation. Although 60 per cent of these patients subsequently relapsed, additional courses of drug or radiation therapy were usually effective, and 63 per cent of the entire group of patients have so far been kept under control without adrenalectomy. (Forty patients have been followed for at least two years after the initial course of treatment.). O,p'DDD produced little gastrointestinal discomfort; an increased serum cholesterol was the main side effect. This drug allows long-term medical management of Cushings disease in most cases. Whether the combination of O'p'DDD with pituitary radiation is the best therapy has not been established.