Activity of the nigro-striatal dopaminergic system during precipitated morphine withdrawal investigated in rats with acute unilateral inactivation of the striatum. The activity of the striatal dopamine system during precipitated morphine withdrawl was studied in rats using a model in which the striatum was unilaterally inactivated by the local injection of KCl. In naive rats dopamine agonists administered just prior to KCL induced ipsilateral turning or circling, while dopamine antagonists in the same situation caused contralateral turning. Withdrawal precipitated by morphine antagonists in rats made dependent by repeated implantation of morphine pellets induced contralateral circling during unilateral inactivation of the striatum. This contralateral circling was only slightly enhanced by haloperidol, but strongly enhanced by a low dosage of apomorphine as well as by some weak dopamine agonists such as CB 154 or By 101. However, high doses of apomorphine completely reversed the withdrawal-induced contralateral circling into ipsilateral circling. Other dopamine agonists, such as d-amphetamine, L-Dopa and piribedil, did not abolish the withdrawal-induced contralateral circling, however, they caused the appearance of an additional ipsilateral circling. Other types of drugs which are known to intensify withdrawal-induced jumping (desipramine, atropine, caffeine) enhanced contralateral circling. There are also other parallels jumping and contralateral circling induced by withdrawal. The direction of naloxone-induced asymmetric behaviour during acute unilateral inactivation of the striatum suggests that striatal dopaminergic activity is reduced during precipitated withdrawal; the other results reported point to the possiblity that extrastriatal dopaminergic mechanisms or different dopamine receptor types within the striatum are involved.


Re-analysis of radiation-induced specific locus mutations in the mouse. A re-analysis of published data on mouse mutation rates induced by X and gamma rays suggests that the kinetics of induction can be analysed by fitting the data to a parabolic curve. We interpret this to mean that a substantial proportion of the induced mutations results from gross chromosomal changes such as deletions, some of which are one-track and some of which are two-track. This analysis is based on the assumption that the shape of the dose curve, which in the female is concave upward, reflects the manner in which the mutations are induced rather than representing a one-track (linear) curve whose shape has been modified by differential repair.


[Maxillary artery to middle cerebral artery anastomosis in dog-- a new experimental model (author's transl)]. End-to-side anastomosis between the maxillary artery and a branch of the middle cerebral artery was performed in the dog. The technique was devised as a new experimental model for extracranial-intracranial arterial shunt operation. The middle cerebral artery was ligated at the origin through a subtemporal small burr hole under the operating microscope in 13 dogs. Then, the shunt operation was carried out in 8 dogs 4 hours after the ligation(acute state), and in 5 dogs 3 weeks after(chronic stage). The patency of the anastomotic site was evaluated by the selective external carotid angiography 2 weeks after the shunt operation. In the acute stage of 8 dogs, 7 cases showed patency of anastomosis (88%), and in the chronic stage of 5 dogs, arteriogram revealed 4 patent anastomosis (80%). In successful cases, arteriogram showed excellent filling of the entire territory of the middle cerebral artery through the shunts (Fig. 4, 5). Various types of experimental shunt operation were attempted in our review of the literature. Among them, the anastomosis between the superficial temporal artery and a branch of the middle cerebral artery by Yasargil (1967) is rather popular and this procedure has been used by some investigators including us to investigate the effect of the extracranial-intracranial shunt on experimental acute stroke. So far as dog's experiment is concerned, the superficial temporal artery appeared to be not suitable for a donor artery, because the superficial temporal artery runs far from the middle cerebral artery and its distal part is extremely small in caliber. Therefore, the superficial temporal artery was often obstructed by compression, kinking or narrowing by surrounding tissues and by adhesion to the bone edge of the burr hole. On the other hand, the maxillary artery of the dog, which is the largest terminal branch of the external carotid artery, has plenty of blood flow and suitable size for end-to-side anastomosis to the middle cerebral artery. In addition, maxillary artery is located very close to the proximal part of the middle cerebral artery. These anatomical and spatial advantage of the maxillary artery seemed to be favorable donor artery to the middle cerebral artery and have brought hight patency rate in our series of anastomosis than that of the other previous experimental extracranial-intracranial shunts. To our knowledge, this is the first report on successful patent shunt formation after long-term occlusion of the middle cerebral artery in animals. Now, it is in our mind that progress of the study can be expected  in the field of extracranial-intracranial shunt operation for cerebral infarction by this experimental procedure.


[Endocrinological evaluation of sellar and suprasellar tumor cases (the seventh report)--endcrinological study on four cases of pituitary adenoma with intratumoral hemorrhage (author's transl)]. Four cases of pituitary adenoma with intratumoral hemorrhage were studied endocrinologically. 1) It would be suggested that ACTH and TSH secretion of these cases was strongly impaired but LH, FSH and PRL secretion was fairly preserved immediately after hemorrhagic episode. 2) Two of these four cases revealed normal TSH secretion and normal thyroid function following the period of excessive TSH secretion and impaired thyroid function.


[Cerebrospinal fluid flow dynamics in cerebral infarction--Numerical study with RI Anger camera (author's transl)]. Although the cerebral blood flow dynamics in cerebral infarction has already been studied by many investigators, the CSF flow dynamics in cerebral infarction has not been well discussed. The purpose of this paper is to investigate CSF flow dynamics in chronic cerebral infarction by RI cisternography and our new quantitative method. In 12 patients with cerebral infarction, the flow of CSF was estimated following intrathecal injection of 169Yb-DTPA or 111In-DTPA. In this study, in addition to the conventional cisternograms, quantitative evaluation of CSF flow was performed in 6 patients by our method. Our previous work included the quantitative CSF flow dynamics in 26 various cerebral disorders using RI Anger camera. This method consisted of following procedure: 30 minutes after RI injection, RI activity was studied continuously for 30 minutes, afterwards playing back the record to calculate the changes of RI activity in the optimal regions of interest. These operations were performed with Anger camera, accessory digital ratemeter and tape-recorder. The changes of RI activity which appeared to be linear is called flow rate in our study for convenience. In this report, the region of interest was selected at Sylvian cistern. 6 patients had abnormal cisternograms consisting of reflux of tracer into the ventricle and delayed migration of tracer to the basal cisterns and diminished flow of tracer in the affected hemisphers. In 5 patients whose cisternograms could not demonstrate the laterality of RI perfsion over the cerebral hemishere, a marked difference of flow rate between right and left Sylvian cisterns was found. These findings probably indicated the correlation between cerebral blood flow dynamics and CSF flow dynamics in cerebral infarction. Moreover, it was confirmed that our method could be of clinical use to evaluate CSF flow dynamics quantitatively. The possible mechanisms of CSF flow disturbance in the affected hemisphere following cerebral infarction was discussed.


[Intracranial collision tumor--A case report (author's transl)]. A 21-year-old man with nasopharyngeal tumor was  first admitted to the Nagoya University Hospital on April 15, 1972. He had difficulty in speaking and swallowing, and developed double vision prior to admission. A soft and yellow tumor was found in the nasopharynx and revealed typical features of chordoma. The patient underwent Co60 irradiation after the operation. On January 25, 1973, the patient developed double vision of severe degree. Microscopic examination of the specimen which was obtained at the time of the second operation in February 9, 1973, disclosed a coexistence (collision) of chordoma and hemangioblastoma. The two different tumors were situated in juxtaposition on histological examination. Co60 irradiation was added during his second hospitalization. Three months after the second operation, he developed symptoms of meningitis and was hospitalized for the third time on June 3, 1973, at which time the tumor tissue extended through the right frontal and middle fossa. The third operation was done with frontal craniotomy and tumor was partially removed. The histological diagnosis was hemangioblastoma. Postoperatively the patient went downhill and died on September 19, 1973. The report of a collision tumor of intracranial chordoma and hemangioblastoma is not found in the previous literature. There have been many theories as to the origin of collision tumor. Some investigators have proposed that the existence of hyperplastic blood vessels within the glioblastoma is responsible for the collision tumor of sarcoma and glioblastoma. Since the advent of radiotherapy, several examples of sarcoma have been discovered at postmortem examination in patient irradiated for treatment of cerebral neoplasm, both gliogeneous and nongliogenous, suggesting a possible relationship between the tumor and the radiation therapy. In our case, the chordoma showed neither hyperplastic blood vessels nor malignant pattern on histological examination. It was suspected that post-operative radiation induced the hemangioblastoma. The etiology was discussed from the review of literature.


[Co-existing aneurysm and arteriovenous malformation--case report (author's transl)]. A patient was presented with both an aneurysm of the frontobasal branch of the right anterior cerebral artery and an arterio-venous malformation fed by the same artery. A 36-year-old man with sudden headache, nausea and vomiting was admitted to the emergency clinic on July, 4, 1974. On admission, he was slightly lethargic and complained of severe headache. The blood pressure was 112 systolic and 64 diastolic. He showed no abnormal findings except for nuchal stiffness and bloody liquor (pressure 260 mmH2o). A right carotid angiogram revealed an aneurysm, 1.0 cm in diameter, on the frontabasal branch of the right anterior cerebral artery and distal to the aneurysm the artery continued to an arteriovenous malformation. No other vascular lesion was observed by other angiographies. On July, 24, 1974, the parent artery (frontobasal branch) of the aneurysm was clipped and the part of right frontal lobe containing the nidus excisted. The patient's post operative course was uneventful.


[Dermoid tumor in left cerebellum--A case report (author's transl)]. This paper describes a dermoid tumor which developed in the dorso-lateral area of the left cerebellar hemisphere. It is the first to be reported in Japan. The patient was a 31 year old female who suffered from severe occipital headaches, frequent vomiting and gait disturbances. Neurological findings on admission included marked bilateral choked discs, horizontal nystagmus on gaze to the left, and poor coordination on the finger to nose test, nose-finger-nose test and and heel-shin test on the left side. Left suboccipital craniectomy was performed. A tumor was found which displaced the left cerebellum anteromedially and inferiorly. The postero-lateral surface of the tumor was adherent to the overlying dura matter. It was completely removed and found to be about the size of a hen's egg. It contained a yellow, porridge-like substance and short hairs. Histological examination of the capsule of the tumor showed stratified squamous epithelium and cutaneous structures, such as hair follicles and sebaceous glands. The diagnosis was dermoid tumors. We could find as many as 78 cases of the posterior fossa dermoids in the literature. In 72 cases (92.4%), the mass existed along the midline in the posterior fossa. The dermoids developed in the cerebellar hemisphere were reported in only 6 cases (7.6%) including the present case. Laterally growing dermoids are considered to be very rare. The pathogenesis is discussed and the literature reviewed.


[Traumatic thrombosis of the internal carotid artery: Report of three cases due to head injury with basal skull fracture (author's transl)]. Three cases of traumatic thrombosis of the internal carotid artery due to head injury with basal skull fracture were reported. The mechanism of thrombosis, the symptomatologic characteristics and the prognosis were discussed with reference to the data in the literature. Four mechanisms by which the condition may be produced include; injury to the intrapetrous or cevernous portion of the carotid artery during basal skull fracture, injury to the point of emergence of the carotid artery from the cavernous sinus as a result of shearing strains suffered at the time of injury, a direct blow to the neck or trauma to the paratonsillar area by a foreign object carried in the mouth, and stretching of the carotid artery by heperextension and lateral flexion of the neck. Secondary symptoms due to thrombosis of the carotid artery after an interval develop most commonly from twelve to twenty four hours. The prognosis in these patients is mostly poor. Therefore, angiography should be performed immediately on any patient suspected of having this lesion and treatment should be considered.


Progesterone action on estrous rhythm in the rat following ventromedial nucleus lesions. Small bilateral lesions of the hypothalamic ventromedial nucleus (SVMN) were produced in 4 day cyclic female Wistar rats by passing a 2 mA cathodic current through stereotaxically oriented platinum unipolar electrodes for 7 sec. The 24 h lengthening of cycle which occurred in 111 our ot 208 females was shown to depend upon lesion placement. Early s.c. injection of 0.75 or 1.5 mg progesterone caused 24 h cycle prolongation more frequently in SVMN-lesioned females with maintained 4 day cycles than in 4 day cyclic unoperated, sham VMN-lesioned, or dorsomedial nucleus (DMN) lesioned females. This effect proved to be related to lesion placement. It was therefore concluded that the VMN is involved in the mechanisms whereby progesterone controls estrous cycle duration in the rat.


The contribution of genetics to biological psychiatry. One of the most striking developments in the framework of biological psychiatry, is the use of human as well as animal genetics' methodology in psychiatric research. After reviewing some basic concepts in human genetic research, we shall present the current status of our knowledge on the genetic determinants of the major psychoses, i.e., the affective psychoses and schizophrenia. The importance of genetic research into psychiatry can also be underscored from a biometric point of view in showing its contribution to the clarification of problem of nosology in attempting to subclassify abnormal behavior on a more etiological basis. Finally, a still open field essential to our comprehension of therapeutics emerges from the study of genetic mechanisms involved in drug metabolism and drug response.


Aortic prolyl hydroxylase and the development of arteriosclerosis in the female breeder rat. Female breeder rats develop arteriosclerosis spontaneously. The primary lesions seen in the early stages of the disease consist of subintimal and adjacent medial ground substance accumulations. With repeated breeding there is extensive elastolysis and calcification in the aorta. In aortae with developing arterial disease, prolyl hydroxylase activity is elevated as is both aortic protein and hydroxyproline, indicative of increased collagen deposition associated with the sclerotic degeneration. As the disease becomes very severe, however, prolyl hydroxylase activity declines, possibly associated with decreased metabolic activity in the severely calcified aorta. Lactation, followed by forced weaning, may condition the development or arterial disease through effect on collagen metabolism. During the first breeding cycle, aortic prolyl hydroxylase activity is elevated for 5 to 10 days after weaning. This increased collagen metabolism in the aorta may be a primary event in the development of the advanced calcific lesions characteristic of the lesions in breeder rats, and may be affected by hormones associated with different phases of the reproductive cycle.


The M. omohyoideus of the mouse as a convenient mammalian muscle preparation.  A study of junctional and extrajunctional acetylcholine receptors by noise analysis and cooperativity. Muscles from cats, rats, guinea pigs and mice have been investigated as preparations for visualizing mammalian neuromuscular junctions with the aid of Nomarski interference optics. The M. omohyoideus of the mouse was found to be most convenient. Electrophysiological investigations showed that an endplate is normally surrounded by a population of perijunctional receptors. For junctional receptors in the endplate, a Hill coefficient of nH = 2.6 for acetylcholine was determined at 38 degrees C, decreasing to a value of 2.3 at room temperature. For both perijunctional and extrajunctional receptors (the latter occurring after denervation), the coefficient nH was 1.9. Noise analysis revealed a channel conductance gamma which changed abruptly from 22.4 +/- 1.0 pS (10--23 degrees C) to 45.6 +/- 3.9 pS (34--39 degrees C) in a very small temperature range around 25.5 degrees C. The mean channel lifetime tau was 0.3 ms at 39 degrees C and 1.0 ms at 23 degrees C.


Renal tubular reabsorption of taurine, gamma-aminobutyric acid (GABA) and beta-alanine studied by continuous microperfusion. Renal tubular reabsorption of taurine, gamma-aminobutyric acid (GABA), and beta-alanine was studied in vivo et situ by continuous microperfusion of single proximal tubules of the rat. In each case, reabsorption was much slower than that for other amino acids that have been studied. With a concentration of 0.1 mmol/l in initial load was reabsorbed over perfusion distance of 3 mm. Taurine reabsorption saturated with only 2.17 mmol/l in initial perfusate. Assuming simple two-parameter kinetics, upper limits for Km of 0.54 mmol/l and forVmax of 0.59 pmol-cm-1--s-1 for tubular reabsorption of taurine were estimated. High (20 mmol/l) concentrations of taurine or beta-alanine in perfusate completely inhibited GABA reabsorption, but L-phenylalanine (20 mmol/l) had no significant effect. The results indicate that the three amino acids are reabsorbed slowly from the proximal tubule by what may be a common transport system. This system appears to have a high affinity but low capacity and to be different from other known renal tubular transport systems for amino acids.


The time course of phosphorylcreatine resynthesis during recovery of the quadriceps muscle in man. The time course of phosphorylcreatine (PC) resynthesis in the human m. quadriceps femoris was studied during recovery from exhaustive dynamic exercise and from isometric contraction sustained to fatigue. The immediate postexercise muscle PC content after either form of exercise was 15-16% of the resting muscle content. The time course of PC resynthesis during recovery was biphasic exhibiting a fast and slow recovery component. The half-time for the fast component was 21-22s but this accounted for a smaller fraction of the total PC restored during recovery from the isometric contraction than after the dynamic exercise. The half-time for the slow component was in each case more than 170 s. After 2 and 4 min recovery the total amount of PC resynthesized after the isometric exercise were significantly lower than from the dynamic exercise. Occlusion of the circulation of the quadriceps completely abolished the resynthesis of PC. Restoration of resynthesis occurred only after release of occlusion.


Evaluation of a neurogenic rapid coronary dilatation during an excitatory response in conscious dogs. The present study was undertaken to evaluate the mechanisms of coronary adaptation to sudden changes in myocardial oxygen demand that occur during excitement. An excitatory response was evoked either by electrical stimulation of the hypothalamic defence area or by noise (discharge of a fire-arm). Continuous measurement of the oxygen saturation in coronary venous blood was used to judge, whether an increase in coronary flow was adequate to match an increased myocardial oxygen demand. During the excitatory response heart rate, cardiac output and coronary flow increased. However, the increase in coronary flow was not adequate to meet the increased metabolic requirement as indicated by a decrease in coronary venous oxygen saturation. In dogs with experimental atrioventricular block, and with heart rate controlled by external pacing, a rapid coronary dilation occurred during the excitatory response and was accompanied by an increase in coronary venous oxygen saturation. This rapid coronary dilation was abolished by beta-adrenergic blockade. The pattern of coronary flow and coronary venous oxygen saturation that occurred during the excitatory response in normal dogs could be mimicked in dogs with atrioventricular block by increasing the ventricular pacing rate. However, when identical increases in heart rate were induced either excitement or by external pacing, the drop in coronary venous oxygen saturation was significantly larger in the paced series. This demonstrates, that an increase in heart rate is responsible for the transient decrease in coronary venous oxygen saturation during the excitatory response. From these experiments it is concluded that a rapid neurogenic dilation of the coronary vessels occurs during the excitatory response. Under normal conditions this rapid neurogenic dilation is masked by the effect of the accompanying increase in heart rate on extravascular coronary resistance.


Elimination of vasopressin by the normal and the damaged liver. Experiments on unanaesthetized normal and thiocetamide treated rats with a note on the influence of ethanol. Arginine vasopressin was infused into the V. portae and into the V. cava of unanesthetized rats in water diuresis. The differential antidiuretic response of the same animal to these infusions was used to calculate extraction fraction of ADH by the liver. In the normal rat no extraction was detected. The liver of rats hydrated with 5% ethanol extracted 10% and that of rats treated with thioacetamide extracted 60% of the ADH infused into the portal vein. It is postulated that disturbances of liver cell function by narcotics and substances causing liver damage may liberate ADH-destroying ferments into the blood.


Effects of saline loading on jejunal absorption of calcium, sodium, and water, and on parathyroid hormone secretion in the rat. To investigate whether intestinal calcium absorption parallels that of sodium following extra-cellular fluid volume expansion, the effects of saline loading on intestinal transport of calcium, sodium and water were studied in rats by perfusing jejunal loops in situ. After calcium-free saline infusion net calcium absorption was reversed similar to that of sodium and water and net secretion occurred. Concurrently, blood-to-lumen (b-l) calcium flux, measured using 45Ca, increased significantly (P less than 0.001). Following expansion with calcium-containing Ringer a similar reversal of net calcium, sodium and water flux was also observed. Again the b-l calicum flux increased but to a significantly lesser extent (P less than 0.05). Plasma ionized calcium remained unchanged after calcium-rich Ringer loading, but decreased significantly (P less than 0.001) when calcium was omitted from the solution. Plasma immunoreactive parathyroid hormone unchanged after expansion with the calcium containing solution but increased following calcum-free infusion. It is concluded that after extracellular fluid volume expansion: 1. net jejunal calcium absorption is decreased; 2. the decrease parallels that of sodium and water; 3. b-l calcium transport is enhanced to a greater degree of calcium-free Rnger infusion than by a calcium-rich solution. This difference could be the result of increased parathyroid hormone secretion.


Renal urate transport during variations in urate synthesis in the rat. In order to determine the effect of intrarenal synthesis of urate upon the urinary urate excretion in the rat, we effected large changes in urate synthesis by increasing it with allopurinol. Hypoxanthine infusion increased plasma urate rapidly and also increased the urinary urate excretion and its renal clearance. However, when the plasma urate was maintained constant, hypoxanthine had no effect upon renal urate transport. Conversely, allpurinol infusion rapidly diminished the plasma urate, urinary urate excretion and its renal clearance. Again, the maintenance of a constant plasma urate concentration prevented any change in urate transport during allopurinol. The urinary degradative purine metabolic pattern was altered predictably by hypoxanthine and allopurinol. Assuming than any putative intrarenal component of urate synthesis would be affected predictably and consistently by hypoxanthine and allopurinol, these results suggest that changes in intrarenal urate synthesis are not an important determinant of urate excretion in the rat.


Fatigue and caffeine effects in fast-twitch and slow-twitch muscles of the mouse. In excised, curarized and massively stimulated fast-twitch mouse gastrocnemius muscles the early twitch tension enhancements (treppe) during 1/s activity between 10 and 36 degrees C increase and affect more contractions as temperature increases. Tension output eventually declines at a temperature-independent rate. Half-relaxation time lengthens below 25 degrees C and shortens above 25 degrees C. During 1/0.63s twitches half-relaxation time lengthens even at 25 degrees C. In slow-twitch soleus muscles activity decreases twitch tension and half-relaxation time regardless of temperature. Activity shortens contraction times in both muscles. Oxygen lack induced by NaN3 cannot account satisfactorily for these results. Activation is apparently more plastic in the gastrocnemius than in the soleus, and the relationship between the rates of their activation and relaxation processes and the temperature sensitivities of these rates also seem to differ. In both muscles caffeine can convert activity-induced shortened of half-relaxation times into prolongations. In the soleus this effect is more pronounced at 30 than at 25 degrees C. At high temperature and twitch rates caffeine reduces treppe amplitude and duration without affecting the eventual twitch tension decline in the gastrocnemius while it greatly accelerates twitch tension decline in the soleus. In both muscles intrafiber Ca2+ movements are apparently major determinants of fatigue behavior.


A continuous-flow, variable mixing valve for perfusion experiments. The device described here continuously mixes two solutions in any required ratio and has been used at flow rates of 6 ml/min in tissue perfusion experiments. Its low-cost construction consists of a three-way miniature solenoid valve driven by a simple electronic circuit. Mixing is stable, reproducible and accurate to +/- 1% of dial setting.


Prophylactic, postinfectious and neonatal vaccination against canine distemper in mink. Mink were vaccinated against canine distemper and challenged with the Snyder Hill strain of canine distemper virus. Protection was acquired if vaccination took place more than a few days before challenge. If vaccination took place even early during incubation mortality was higher than in the unvaccinated controls. Full protection of kits may be achieved even at an age of 16 to 20 days provided the kits had not passively acquired immunity from their mothers. Kits surviving distemper because of passively acquired immunity may not actively acquire immunity during infection and may die at a later exposure.


[The receptor of adenosine-dephosphate on the human platelet membrane (author's translation)]. The binding of 14C-ADP on the isolated platelet membrane is a saturable and reversible phenomenon which seems to implicate a protein only partially solubilised by Triton X-100. The binding is strongly reduced by mersalyl, which is known to inhibit the ATPase activity of the thrombosthenin i.e. the platelet contractile protein; this protein could be involved in the mechanism of binding of ADP on the platelet membrane. Platelets not aggregated by ADP from patients with Glanzmann's thrombasthenia, have a normal binding of 14C-ADP which is also strongly reduced by mersalyl.


[Clinics and genetics of Glanzmann's thrombasthenia (author's translation)]. Glanzmann's thrombasthenia begins in infancy. The most important clinical signs are cutaneous and mucous hemorraghes (purpura, epistaxis, bleeding gums, menorraghia after puberty). The disease proceedes by alternate periods of activity and remission, the frequency and severity of which decrease with age. Death occurred during any of the attachs. Our 10 cases (7 girls, 3 boys) were in 5 "Manouche" gypsies sibships, interrelated by consanguineous marriages. Genetic studies demonstrated that the disease was inherited in the autosomal recessive pattern. The detection of heterozygotes is now possible with an antibody which appeared in a thrombasthenic patient. This antibody agglutinated the normal platelets, but not the ones of thrombasthenic patients. In heterozygotes the agglutinating effects is intermediate between the homozygote and normal.


Central action of ergometrine.

Central action of ergometrine. Ergometrine, a spasmolytic which also stimulates dopamine receptors, was investigated as a potential central stimulant. It did not influence the locomotor activity of normal rats and mice, and in high doses even depressed it. The locomotor activity depressed by reserpine, spiroperidol, and pimozide was elevated by ergometrine. Ergometrine antagonized neuroleptic-induced catalepsy and abolished ptosis and hypothermia produced by reserpine. Given alone ergometrine depressed the body temperature in rats and mice, and this effect was abolished by pimozide in both species, and by spiroperidol and haloperidol in mice. The hypothermia was not antagonized by atropine. In several respects the central action of ergometrine resembles that of apomorphine.


Spectrum of pharmacological actions on brain dopamine. Indications for development of new psychoactive drugs. Discussion of amantadines as examples of new drugs with special actions on dopamine systems. Amantadine (D1) and 1,3-dimethyl-5-aminoadamantane (D145) as examples of new drugs with special actions on dopamine systems are discussed. D1 or D145 decreased significantly apomorphine or amphetamine-induced stereotypy in rats but in experiments with chronic pretreatment with amantadines -- potentiation of stereotypy was observed. D145 (20 mg/kg) abolished stereotypy in these conditions. In biochemical experiments D1 or D145 were neither like apomorphine nor like amphetamine. Its concluded that D1 and D145 in addition to their amine releasing properties have the ability partially to occupy the dopaminergic receptor.


[Pickwickian syndrome and hypersomnia with periodic respiration]. A classical definition of Pickwickian syndrome associates alveolar hypoventilation, obesity and hypersomnia with periodic breathing. Obesity in itself is enough to explain the alveolar hypoventilation and some of the sleep disorders, but in fact all three elements of this syndrome are intricated. Obesity, whether associated with a Pickwickian syndrome or not, affects ventilatory mechanics similarly. With the cause of sleep disorders are associated central ventilatory pauses, appearing periodically followed by phases of apnoea secondary to buccopharyngial hypotony. The alveolar hypoventilation is therefore the consequence of obesity and periodic apnoea. It also results from a low respiratory frequency considering that the tidal volume is also decreased. These different elements suggest some disorder of the centers controling ventilation. One can describe different nosological forms, all having as a common factor hypersomnia with periodic respiration, the latter being a determining factor in the diagnosis. Therapy, including weight reduction and symptomatic treatment of alveolar hypoventilation, is now augmented by new drugs acting on the central nervous system.


The effect of bradykinin on central dopamine receptors. Bradykinin (BK) injected intraventricularly (ivc) at doses of 0.25-0.5 mug per rat potentiated the depth of fluphenazine catalepsy and depressed or abolished the symptoms of sterotypy produced by amphetamine or apomorphine. BK did not affect the level of dopamine (DA), but elevated the level of homovanillic acid in the brain, and accelerated DA turnover as measured by the rate of dopamine disappearance following treatment with alpha-methyltyrosine. The results suggest that BK inhibits the central dopamine structures by blocking the DA receptors.


Influence of albumin degradation products (ADP) on the central action of catecholamines. The influence of ADP on the central action of catecholamines was investigated. ADP abolished the central action of noradrenaline, amphetamine and nialamide. The peptides decreased apomorphine stereotypy and enhanced haloperidol induced catalepsy. These results support our previous suggestions [10-14] that ADP acts on the CNS by antagonizing the action of central catecholamines.


Effect of angiotensin on the central action of dopamine. Angiotensin given intraventricularly enhances amphetamine but not apomorphine-induced stereotypy 30 min. after peptide administration. Simultaneous injection of angiotensin and dopamine increases amphetamine -- while decreases apomorphine -- induced stereotypy. The stereotypy produced either by apomorphine or amphetamine in rats pretreated with Ro 4-4602 + L-DOPA was diminished by angiotensin. Angiotensin elevated haloperidol-induced catalepsy. A possibility that angiotensin may inhibit both release and uptake of dopamine by nerve endings is discussed.


Hormones and regional brain blood flow.

Hormones and regional brain blood flow. Acute effects of the hormones, estradiol-17beta and alphaMSH, and of neonatal pretreatment with alphaMSH on the flow of blood to regions of the brains of conscious adult rats have been determined with an indicator distribution technique. As previously reported, flows were reduced in most areas within 10 min after intravenous administration of alphaMSH; only the occipital cortex was spared. Though these effects were transitroy for most areas, perfusion of pons and medulla, cerebellum, hippocampus and parietal cortex was still low by 20 min. However, pretreatment with alphaMSH during infancy led to persistent behavioral changes which were not accompanied by flow differences. Assuming that flow changes reflect functional changes, the rapid responses to alphaMSH suggest an explanation for the effects of this hormone on visual learning and on the determination of subsequent learning behavior. By contrast, estradiol, within 10 min after injection, increased flow to most regions of the brain, especially the frontal cortex, hippocampus, basal ganglia and cerebellum; females were more affected than males. Flow changes were greater than those elicited by more obvious behavior-modifying drugs. Compared to alphaMSH, the flow data for estradiol suggest a physiologic basis for a behavioral effect which is likely to be different yet, perhaps, equally profound.


Hexobarbital sleeping time in the rat: effects of isolation and lesions of the locus coeruleus. Hexobarbital sleeping time was observed in isolated and nonisolated rats with lesioned locus coeruleus (LC). Isolated animals were divided into 2 groups: aggressive (killers) and indifferent (nonkillers). Each group included rats with no lesion, with sham lesion and with LC lesion. Hexobarbital sleeping time was prolonged in nonisolated male, but not female, rats with lesioned LC (7 and 14 days after the lesion). This effect was not observed in animals previously isolated for 3 weeks. These results suggest that the LC plays an important role in the mechanisms of barbiturate sleep, but this effect may be related to the emotionality of animals.


Effects of monoolein on hydrolysis of triglyceride by lipoprotein lipase in the presence of an inhibitory apolipoprotein. The previously demonstrated inhibition of cow's milk lipoprotein lipase by apoLp-Ala and the deinhibition by monoglyceride have been studied in more detail. The apoLp-Ala inhibition is reversible by the addition of monoglyceride before or after enzyme additions. Quantities of monoglyceride accumulate during hydrolysis of triglyceride which are adequate to prevent inhibition by added apoLp-Ala. Accelerating reaction rates observed when the substrate contains the apoprotein at levels producing partial inhibition are also explained by monoglyceride production. These effects were observed with both crude preparations of skim milk and highly pruified lipase. It is suggested that the generation of monoglyceride may be important in facilitating hydrolysis of triglyceride in lipoproteins containing this inhibitory apolipoprotein.


A simple method for counting antibody bound labelled steroids. A simple method is described for the counting of tritiated antibody-bound steroid after acidification and extraction into a toluene based scintillant. The resulting count rate is stable and quenching is minimal. The method give improved count rates when compared with methods employing scintillants containing methanol, dioxane, or Triton and compares favourably with methods involving pre-heating of antibody-bound steroid or extraction of free steroids after the addition of ammonium sulphate. A specific antibody for estradiol has been used to illustrate the application of the technique to antibody titration curves and standard curves.


O-(Carboxymethyl)oxime steroidal haptens linked in the C3 position: study of the characteristics of antibodies against 17alpha-hydroxyprogesterone and testosterone and of their evolution with time. The production of highly sensitive and specific antisera against 17alpha-hydroxyprogesterone (17 OHP) is reported. 17 OHP was rendered antigenic by covalent linkage to bovine serum albumin through position 3 of the steroid. An unambiguous method to prepare the mono-3-0-(carboxy-methyl) oxime derivative (CMO) of 17 OHP is described starting from 17 OHP-acetate. Antisera raised in rabbits were of high affinity for 17 OHP (Ka = 1 to 2 x 10(10) L/mole) and showed very little (less than 0.7%) or no cross reaction with a variety of steroids. Cross-reaction with 17alpha-hydroxy pregnenolone was however significant. When studied in relation to time, cross-reaction of the latter steroid decreased significantly (18 to 2%) while Ka remained at the same level. The same study of the evolution with time (up to 600 days) of the characteristics of antisera raised against the 3 CMO derivative of testosterone is also reported.


[Protein SH-group concentration and RNA synthesis during the process of induction of proliferation in the stationary phase of cell culture growth]. The dynamics of intracellular protein SH-group (PSH) content was studied cytochemically in the course of stimulation of cell proliferation in stationary cultures of an established Chinese hamster cell line and of human diploid embryo fibroblasts. The results were compared with the pattern of RNA synthesis during the prereplicative period. In Chinese hamster cells immediately after medium changing in stationary cultures there is an augmentation of PSH content in parallel withe the increase in RNA synthesis rate. Later on, the rate of RNA synthesis and PSH content are seen decreasing followed by a new increase in the rate of RNA synthesis correlated with the second rise in PSH content. In stationary cultures of human diploid fibroblasts, there is also an increase in the rate of RNA synthesis and in the content of SH after medium changing, but the second wave of RNA synthesis and the second rise in PSH content are not pronounced. The variation in PSH content reflects the shift in the cell metabolism during the prereplicative period and is not attributed to changes in cell protein content.


[Changes in the cytochemical properties of chromatin after stimulating proliferation in a stationary culture of Chinese hamster cells]. The first part of the prereplicative period in stimulated for cell proliferation steady-state culture of Chinese hamster cells was studied cytochemically. Investigation of the binding pattern of basic dye Acridine orange and Actinomycin D with cell nuclei and the melting profile of chromatin in situ suggests that one of the early events occurring in the course of stimulation of cell proliferation in steady-state culture is chromatin activation, i.e. changes in its physicochemical properties resulting in augmentation of transcription.


[Analysis of total lactate dehydrogenase isoenzyme activity in mouse ova during clevage]. The total activity of lactate dehydrogenase isoenzymes was detected in the intact ova of mice during the clevage and, in particular, blastomeres at the 2-cell stage. Routine histochemical technique was employed in addition to microspectrometry. During the clevage, the ova differ in their enzyme activity. At the 2-cell stage there are ova with similar reaction in both the blastomeres as well as those with different enzyme activity in each blastomere.


[Ability of bovine fibrinogen to accept and retain plasminogen proactivator specific for human blood]. The plasminogen proactivator present in human plasma and retained by purified human fibrinogen preparations is readily accepted and retained by bovine fibrinogen. This "transplantation" makes isolated bovine fibrinogen susceptible to streptokinase. The latter induces degradation of isolated bovine fibrinogen resulting in characteristic fragment formation. Our experimental results, particularly those showing the inability of bovine plasminogen (applied in a great excess) to remove the acquired proactivator from bovine fibrinogen, give indirect evidence that the proactivator function is not a specific property of the human plasminogen but that of some other substance.


Parkinsonism and neurogenic bladder. Experimental and clinical observations. In a group of patients suffering from Parkinson's disease, beside neurogenic bladder dysfunction, we have also found dysfunction affecting the external sphincter musculature. Treatment with L-Dopa probably improves the urethral symptoms by providing a relaxing effect on the urethral closure pressur together with better coordination of the pelvic floor and external sphincter Mechanism during micturition. The effect was parallel to the improvement in Parkinsonion symptoms. Experimental studies demonstrate the ability of L-Dopa to reduce urethral closure pressure and this effect was related to a central effect on the skeletal musculature.


The importance of gonadothropin assays in the clinical follow up patients with germinal tumors of the testis. Clinical-hormone studied were done on 34 patients with germinal tumors of the testis. The gonadotropin titres varied from normal to highly elevated values. Only in 4 cases (11.77%), however, were the gonadotropin titres above 10,000 mouse units/24 hours. These 4 were among the 9 cases (26.47%) with positive pregnancy tests. Gynaecomastia was present in 4 patients (11.77%). Total estrogens were assayed in these 4 cases and were found to be high. Gynaecomastia is attributed to excess estrogens. Elevated gonadotropin titres were found predominantly in cases of embryonal carcinoma, teratocarcinoma and choriocarcinoma, as well as in the most advanced clinical stages. As regards the correlation between gonadotropin titres and course of the tumor, it was found that the higher the titre the worse the prognosis. The results suggest that hormonal assays are of value in the clinical follow-up of testicular germinal tumors and should therefore be carried out in association with other clinical parameters.


[Lasers in the treatment of arterial occlusive diseases of the limbs]. The authors have analysed the initial results of treatment in 64 patients suffering obliterating diseases of arteries of upper and lower extremities by means of irradiation with a helium-neon laser the least electric resistance points. The control over the results of treatment is exercised basing on findings of thermovision study and patients' subjective sensations. The best results were gained in treatment of patients with Reynaud diseases and obliterating endarteritis. The therapy employed yielded an insignificant effect in various forms of atherosclerosis of the lower extremities.


Oestrous behaviour in a herd of dairy cows. A group of 60 housed Friesian cows were observed continuously for a period of 25 days, during which time all cows were recorded for incidence of mounting activity and 18 selected cows were recorded for various aspects of maintenance activity. All 60 cows were judged as showing oestrus. Average duration of oestrus (+/-SD) in 33 cows was 14-9 +/- 4-7 hours, and the cows were mounted 56-3 +/- 34-8 times. The greatest mounting activity was associated with the night hours. There was no diurnal pattern of onset of oestrus. The majority of mounting activity (79 per cent) occurred in the cubicle area of the building. Comparison of maintenance activities showed that oestrous cows spent, on average, less time standing in a cubicle (P less than 0-01), lying in a cubicle (P less than 0-001) and more time standing elsewhere (P less than 0-001) than non-oestrous cows. The results are discussed in relation to oestrus detection.


Effect of lactation on the immune response to gastrointestinal nematodes. The immune expulsion of gastrointestinal nematodes is impaired during lactation by the inhibition of the lymphocyte mediated component. As a result the population of worms may increase. At the same time, the fecundity of female worms in previously immune hosts may increase to approach that of worms in fully susceptible animals. There is good evidence that these events are primarily endocrinal in origin but although prolactin is probably involved, certain anomalies exist. These may reflect differences in the secretion pattern of the hormone in different phases of reproduction or they may indicate an interrelationship with a second hormone, for instance, adrenal glucocorticoids.


[Transplacental blastomogenic effect of N-nitrosomethylurea in rats with constant estrus]. As a result of transplacental exposure of rats of NMU in the dosage of 20 mg/Kg (intraperitoneally) on the 21st day of pregnancy tumors in the offspring developed in 6 to 16 females and in 10 of 17 males. In rats with persistent estrus, induced in sex mature females by their castration and one-moment autoimplantation of ovaries in the tail, tumour developed in 25 of 41 animals. In combination of transplacental effect of NMU and postnatal induction of persistent estrus in females neoplasms were recorded in 14 of 17 animals, the incidence of neoplasms of the nervous system and kidney observed only after transplacental NMU exposure of males being increased. Hormonalmetabolic shifts observed in rats with persistent estrus seemed to potentiate transplacental blastomogenic action of NMU.


[Change in the adrenocortical function of the adrenals and activity of several intracellular enzymes involved in nitrogen metabolism in experimental hypothermia]. An increased content of adrenaline was observed in rabbit adrenal glands under the conditions leading to a decrease of rectal temperature. At the same time the activities of aspartate- and alanine aminotransferases in liver hyaloplasm and ornithine carbamoyl-transferase in mitochondria were decreased, while the activity of the transaminases in mitochondria was maintained unaltered. After the recovery of the temperature the content of the hormone still exceeded the normal level; function of the enzymes studied was distinctly intensified in all the subcellular fractions of hepatocyte. Content of 11-hydrocorticosteroid, being unaltered distinctly in overcooling, was markedly decreased within the later period. Membrane and substrate interrelations, apparently responsible for the biochemical alterations observed, are discussed.


[Creatine biosynthesis in mice with hereditary muscular dystrophy: possible defect in liver plasma membrane adenyl cyclase]. Activity of enzymes responsible for creatine biosynthesis (transamidinase, EC 2.1.4.1., and guanidine acetate methyltransferase, EC 2.1.1.2.) was studied in homogenates of pancreas, kidney and liver tissue of mice in normal state and in hereditary muscle dystrophy (129/Re-dy). Simultaneously, the activity of guanidine acetate methyltransferase from liver tissue was studied after addition of glucagon and ardenaline. In normal healthy mice homogenates of liver tissue distinctly increased the activity of guanidine acetate methyltransferase if glucagon and adrenaline were used in physiological concentrations. At the advanced stage of mice hereditary myodystrophy liver homogenates lost their capacity to activate the enzyme after addition of the hormones. The data obtained suggest that adenyl cyclase is impaired in plasmatic membranes of liver tissue, which mediated, using cAMP,the transformation of hormonal signals affecting the intracellular synthesis of creatine.


[Notifiable and non-notifiable infectious diseases in the federal republic of germany (author's transl)]. Owing to the growing density of population, urbanization, and the use of all kinds of publicly accessible facilities, the interruption of the infection chain for air-borne diseases proves particularly inadequate if no efficient prophylactic inoculations are available to combat viral infections or if no efficient chemotherapeutical measures can be adopted against bacterial infections. Equally problematic is the struggle against salmonellosis associated with the mechanized mass production and distribution of foodstuffs as well as the forms of infectious hospitalism, especially hepatitis B, which are favoured by the technical advances in the medical field. Venereal diseases prove highly resistant because the human patterns of sexual behaviour are difficult to influence. Thus the infectious diseases caused by deficient hygiene have virtually disappeared in our country, while those diseases survive or occur which are capable of profiting from the sociological changes and the technical progress of civilisation. On the whole, the mortality rate has drastically dropped while morbidity has remained more or less the same (with, however, a change in the spectrum of the infectious diseases); this is due mainly to mass inoculation and specific therapy.


[New topics in infectious medicine (author's transl)]. After the eradication and control of the old classical epidemics, the situation in the sector of infectious diseases has changed. These days 3 groups of infectious diseases have gained importance than they had in the past and thus have changed the scene: I. Infectious diseases which earlier were either not known on such a scale or completely unknown Under this group fall mainly the "infectious factor diseases" caused by so-called "opportunistic" germs, mixed infections, old and new zoonoses, iatrogenic infections, "explosion epidemics" and epidemics caused by germ mutations. II. Therapy-resistant infectious diseases Here a distinction is made between infectious diseases caused by chemotherapy-resistant germs and the diseases whose increased rate of incidence is due to the fact that the arthropod vectors became resistant to insecticides. III. Infectious diseases to which the classical Henle-Koch postulates no longer apply These are chronic diseases and persistent infections, immunopathogenic consequences of infections and viral tumours. The diseases are discussed separately with respect to the cause/effect relationship with the emphasis on the following subjects: Opportunistic problem germs, infectious factor diseases with hospitalism, mixed infections, salmonellosis and new viral zoonoses, chronic diseases, "slow viruses", immunopathogenic consequences of infections and viral tumours.


[Immunologic response ot introduction of intact and formalinized erythrocytes]. Experiments were conducted on mice; there was revealed an increase in the immunogenicity of erythrocytes following their immunization illustrated by the difference in the circulating antibody titres and the plaque count in the spleen of the animals, and also by the results of immunization with formalin-treated erythrocytes mixed with the cells of the peritoneal exudate. A conclusion was drawn on the expediency of the immunization with formalinized erythrocytes of rabbits--producers of the hemolytic serum.


[Effect of group and isolated rearing of white rats on their resistance to exposure to emotional stress]. The influence of isolated vs. group breeding on the sensitivity of higher nervous and vegetative functions to chronic stress effects was studied in 50 albino random-bred male rats. It has been found that group breeding of the animals (ten specimens in each cage) from the 12th to the 30th week of their life enhances their resistance to external stress factors which begin to take effect from the 17th week on. The effect is linked to the positive emotions produced by mutual contacts among the animals and their intensified motor activity. Isolated breeding of the rats (beginning with the 17th week of their life) makes them vulnerable to the action of stress situations. By the end of the investigation they exhibit clear symptoms of an early stage of neurogenic hypertension. The isolation evidently sets up a negative emotional background, reduces drastically the motor activity and lowers the animals resistance to extreme environmental influences.


Effect of sodium fluoride on glycolysis in human erythrocytes and Ehrlich ascites tumour cells in vitro. In human erythrocytes and Ehrlich ascites tumour cells, NaF inhibites aerobic glucose utilization and lactate formation. The inhibition of glycolysis was accompanied by a decrease in cellular pyruvate and ATP, and by accumulation of 2-hosphoenolpyruvate. These results and direct enzymatic determinations showed that fluoride inhibits, in addition to enolase (phosphopyruvate hydratase, EC 4.2.1.11), also pyruvate kinase.


[Glucose tolerance of postnatally stress-sensitized albino rats following chronic emotional stress in adulthood]. Male albino rats were used to study the effect of electrical stimulation in the postnatal phase (day 1--15) leading to short-time convulsions and cyanosis lasting about 10 min in 5-month-old animals upon the development of glycemic dysregulation induced by emotional stress. The studies involving i.p. glucose administration show that a 3-week stress influence on postnatally stimulated animals caused heavier changes of glycemic regulation than with non-pretreated animals. These results suggest a stress sensitization occurring in the postnatal phase and are discussed in connection with the "stress-sensitive risk personality" by R. BAUMANN. Further studies have shown that the postnatal stress sensitiveness is reversible and cannot only be compensated by a rest period of several weeks but may even cause stress resistance on renewed stressing for three weeks.


[The role of uncertainty in the conditioned-reflex learning behavior for selected cardiovascular functions]. As a contribution to quantitative analysis of exogenous stress action, the role of probability learning (probability stress, probability affirmation) for selected cardio-vascular functions was studied in 25 albino rats and 8 dogs. It has been shown in the rats learning with probability stress that a dependence exists between stress probability, on the one hand, and conditional-reflectory processes and systolic blood pressure rise, on the other, that is, the pathogenic action of probability stress increases from a probability of p = 1.0 to p = 0.5. An analogous picture was found with the probability affirmation being applied in dogs. While a probability affirmation with p = 1.0 promoted adaptational processes, a value of p = 0.5 led to experimental neurosis, tachycardia and ECG alterations. The results obtained are discussed in context with the information entropy and information theory of emotions.


Variations in the spontaneous activity of the uterine muscle in vitro and in situ and its response to oxytocin. A study is made of the contractile and bioelectrical activities of the uterine muscle of guinea-pig in vitro and of rabbit in vitro and in situ, as well as their Oxytocin-induced changes upon different balance of the ovarial hormones. In rabbits in situ the uterine muscle contractions are longer and are recorded with a slower rhythm than in vitro. Both in situ and in vitro the sensitivity of the myometrium to Oxytocin is lower upon domination of progesteron and higher upon domination of oestrogen. In guinea pigs the myometrium is least sensitive to Oxytocin in the juvenile animals as compared with the sexually mature ones. The sensitivity of the guinea-pig myometrium to oxytocin in the various phases of the oestral cycle is weakest during dioestrus and strongest during oestrus.


Pharmacological analysis of certain mechanisms of morphine addiction. The effects of L-Dopa, Methysergid, Diphenhydramine hydrochloride and LSD on the development of morphine dependence and the abstience syndrome after its withdrawal, were tested in experiments on 200 male Wistar albino rats. L-Dopa had no efect on the development of physical morphine dependence, while Methysergid prevented its development. Applied in rats during the abstinence syndrome, LSD intensified their aggressivity with no influence on the analgesic effect of morphine. Diphenhydramine reduced the aggressiveness of the rats during the abstinence syndrome. Biochemical tests show that in morphine-tolerant rats there was an increase in the content of brain serotonin, less of dopamine and no changes in noradrenaline. The significance of the brain levels of serotonin, dopamine and noradrenaline for the development of physical morphine-dependence is discussed. It is pointed out that serotonin and dopamine play an important role both for the origin of the physical morphine dependence, and in the abstinence syndrome after its withdrawal.


Experimental and theoretical analysis of oxygen transport in fetal brain. Based on the results obtained in this study and the results of others it seems safe to conclude the following: 1) Fetal brain PO2 values are considerably lower than those found in adult brain. 2) Administration of 100% oxygen to the mother can (but not always) significantly raise the PO2 at a specific point in the fetal cortex. 3) The response of fetal brain PO2 to changes in maternal arterial PO2 is delayed by a finite quantity of time of the order of magnitude of 38 seconds. 4) The time required for the fetal brain PO2 to reach a minimum following a decrease in the PO2 of maternal arterial blood coincides closely with the time required for the maternal arterial PO2 to reach its minimum plus the pure transport delay time (38 seconds). 5) The fetus has available a control mechanism which acts to compensate for periods of reduced PO2 in the microenvironment of the fetal cortex.


Compositional data on some Persian bezoars. Fourteen Bezoars from Persia, used in past times and even to-day as a medicine or as a health-preserving precious tone, are examined. Among the concretions ellagic acid prevails. Some are bile pigmented or calcite stones. Other bezoars are mineral substances or artifacts.


The rapid onset of inhibition of antibody-forming cell proliferation upon an increase in density of cellular suspensions cultured in vitro. It was shown previously that the development of primary immune response in vitro in the Mishell-Dutton system was strongly inhibited by increased cell densities (Gurvich et al., Immunology 1975. 28: 271). In the present work, the rate of onset of this inhibition was studied in C57BL/6 mouse spleen cell suspensions during the phase of exponential increase of antibody-forming cells (AFC) after 3 days' cultivation in vitro with the antigen. It has been shown that the increase in AFC number is very soon inhibited following an increase in the cellular density, the inhibition already being evident within 2 or 4 h. Parallel reduction in incorporation of radioactive precursors in DNA and especially RNA is observed, whereas inhibition of protein synthesis was delayed.


Retinal detachment secondary to branch vein occlusion: Part I. Eight patients with retinal detachment secondary to branch vein occlusion were studied. Retinal detachment secondary to branch vein occlusion occurs when the vein occlusion is severe and there is marked capillary nonperfusion and leakage. The detachment is limited to the area of the occluded vein and does not extend beyond the equator. Usually the detachment is shallow; however, it can be bullous as demonstrated in 3 of our patients. Fluorescein angiography revealed the typical findings associated with branch vein occlusion, in addition to late pooling of the dye into the fluid in the subretinal space. In each of the 6 cases treated by laser photocoagulation, reattachment of the retina occurred. The disease is discussed from the standpoint of ocular findings, fluorescein angiography, diagnosis and differential diagnosis, course, treatment, and prognosis.


The possibility of a flaw underlying Weinberg's differential rule. There seems rather good evidence that there is a flaw underlying Weinberg's Differential Rule, and that among DZ twin pairs, there are perhaps eight same-sexed pairs to every seven opposite-sexed pairs.


Paternal age, stillbirths and mutation.

Paternal age, stillbirths and mutation. Previous suggestions that accumulation of mutations in the germ line of ageing fathers causes an increased stillbirth rate were based on analyses of data which were heterogeneous for social variables whose effects were confounded with possible paternal age effects. This study was confined to the analysis of stillbirth rates of groups of women selected to be homogeneous for education, previous pregnancy outcomes, age, race and marital status. It is concluded that stillbirth rates do not increase with father's age independently of maternal variables. Neither accumulation of mutations in the paternal germ line nor other biological change associated with father's age can be inferred to cause an increase in risk of stillbirth with increasing paternal age.


Variety of 2,4-D metabolic pathways in plants; its significance in developing analytical methods for herbicides residues. 2,4-D in plants very rapidly undergoes various transformations and its predominant metabolic pathways and rates vary with different plant species. In bean and soybean plants major 2,4-D metabolites are 4-O-beta-D-glucosides of 4-hydroxy-2,5-dichloro- and 4-hydroxy-2,3-dichloro-phenoxy-acetic acids; in addition, considerable amounts of N-(2,4-dichlorophenoxyacetyl)-L-aspartic and N-(2,4-dichlorophenoxyacetyl)-L-glutamic acids are accumulating in them. Among 2,4-D metabolites in cereals there prevailed 1-O-(2,4-dichlorophenoxyacetyl)-beta-D-glucose while the glycoside of 2,4-dichlorophenol prevailed in strawberry plants.


[Role of central catecholamines in the psychostimulant activity of pyrovalerone]. A comparative study of the effects of alpha methylparatyrosine (alpha MPT) and/or reserpine pretreatments on mice motorhyperactivity and rat stereotyped behaviour induced by pyrovalerone and amphetamine suggests a different mechanism for these two substances. Both behavioral effects were abolished by alpha MPT but not altered by reserpine in the case of amphetamine which presumably acts through a selective release of "newly synthesized" catecholamines from a "functional" pool. In contrast to this, pyrovalerone would increase spontaneous motor activity through a preferential release of norepinephrine from a "storage" pool since motorhyperactivity was not altered by alpha MPT especially during the first phase, whereas it was abolished by reserpine. Stereotyped behaviour induced by pyrovalerone, was still present after pretreatment with alpha MPT or reserpine; these data suggest an action through a release of both "newly synthesized" and "stored" dopamine. On the other hand, a direct action on dopamine receptors might be involved after high doses of pyrovalerone and amphetamine since stereotyped behaviour was found to be present after a combined pretreatment with alpha MPT + reserpine.


[The "mycoplasma pneumoniae" in pathological respiratory processes. Serological disease (author's transl)]. The AA. present the results obtained determining by the F.C. test the antibodies for respiraotry viruses and for Mycoplasma pneumoniae over 1112 patients, of which 742 affected with pathological respiratory processes, during the period 1971-1975. 104 patient have shown a significant correlation between respiratory disease and antibody movement for M. pneumoniae. They have been classified according to their clinical-radiological properties as follows: 38 affected with pneumonia; 37 affected with pleuritis; 29 affected with tracheobronchitis. Particularly interesting is the range of occurrence of the disease: we have noticed a high incidence in the period 1971-1972, followed by an almost complete disappearance of pathological instances in the period 1973-first semester of 1975, and signs of a new recrudescence in the second semester of 1975. These data have been confirmed also by investigations carried out among healthy people. It has also to be pointed out the possibility of family's epidemicity, and the AA. report two epidemic cases under personal observation.


A note on the kinetics of uptake of D-glucose by the food yeast, Candida utilis. Unlike other yeasts so far investigated, the D-glucose carrier of Candida utilis (strain NCYC 737) appears to change affinity for D-glucose according to its exogenous concentration. When the concentration of D-glucose was less than 0.4 mM, the apparent Km approximately 0.2 mM; at greater than 0.4 mM, the Km approximately 10 mM.


[Relationship between the limbic system and gonadal function. Quantifiable morphokinesis of the medial amygdaloid nucleus with reference to the estrous cycle]. Karyovolumetric investigation showed that in rat the neurons of the limbic system which are associated with the Pars caudalis of the nucleus amygdaloideus medialis followed a morphokineses which was quantifiable in relation to the oestral cycle. The cell nuclei differed significantly in volume between cycle phases, which was interpreted as morphological correlation between variations in neuronal activity of metabolism. It was thought to be another point in support of the relationship between the amygdala and central-nervous structures of the cerebro-pituitary-gonadal axis.


Synthesis and biological properties of derivatives of 3-methyl-5-aminoisothiazolo-4-carboxylic acid. The reaction of 3-methyl-5-aminoisothiazolo-4-carboxylic acid with the chlorides of chloroacetaic acid and chloropropionic acid gave 3-methyl-5-chloroacetyl- and 5-chloropropionylisothiazolo-4-carboxylic acids, which upon heating in anhydrous ethanol with aliphatic and aromatic amines gave the respective 5-aminoacetyl and amino-propionyl derivatives of these acids. Iodoacetyloaminoisothiazolo-4-carboxylic acid in reaction with ammonia was converted in 3-methylo-5-aminoacetylo-aminoisothiazolo-4-carboxylic acid, which upon heating in toluene with isocyanates and isothiocyanates gave the respective derivatives of urea and thiourea. Some of the synthesized compounds showed psychotropic and cytostatic activity.


[Protein utilization of mixed feed rations in lactating pigs with reference to the essential amino acid content of the feed proteins. 2. Report. Utilization of the feed proteins in the use of soy bean extraction residue, waste liquor yeast, horse bean meal fish meal and maize gluten for a basic ration]. Nitrogen trials were performed on lactating pigs to investigate the utilization of protein from some feeding rations. The basal ration fed to the sows consisted of ground barley+oats+flaked potatoes or ground barley+sugar beet chips. The basal ration was supplemented with a protein source. The protein feeds used were extracted soya bean meal, horse bean meal, fish meal, maize gluten and waste liquor yeast. Data for the average biological value of the dietary proteins were as follows (in the given order of protein feeds): 61%, 59%, 54%, 58% and 37%. PPV data were: 44%, 43%, 39%, 44% and 28%. The proteins of nearly all rations were deficient in lysine when compared with the range of amino acids present in the proteins of sow milk.


[The substitution of protein feed by lysine supplemented protein-rich wheat during the raising and laying periods of hens. 7. Report. Determination of the true digestibility of amino acids with and without lysine supplement in the feed]. In the present paper regression techniques were used for determing the true digestibility of amino acids from lysine-supplemented rations fed to laying hens as compared with unsupplemented rations of the same composition. 5 groups of 4 hens each were investigated receiving graded amounts of food and nutrients. The daily amounts of pellets fed per bird in group 1 to 5 were 120 gms, 100 gms, 80 gms, 60 gms and 40 gms. The quantity of lysine contained in 100 gms of the pellets was 664 mg in ration 1 and 554 mg in ration 2, the corresponding N values being 2.57 gm and 2.62 mg. The total amount of endogenic amino acids excreted per day was 128 mg per kg of body weight in birds receiving the lysine-supplemented ration and 132 mg per kg of body weight for the lysine-deficient ration. Data for the true digestibility of lysine and isoleucine were significantly higher in the case of the lysine-supplemented ration than with the lysine-deficient mixture. Lysine values were 86% and 75%, the corresponding lysine data in crude faecal proteins 4.8% and 7.1%. Generally speaking, the crude faecal protein of hens fed the lysine-deficient diet contained higher proportions of most of the essential and non-essential amino acids.


[The replacement of skim milk in the diet of young pigs with an extremely short suckling period. 3. Report. Use of liquid substitute feed on the basis of skim milk, fish meal and wheat under production conditions]. A trial was performed in which 273 piglets received a liquid milk diet between the 12th and 30th day of age. This was compared with a liquid experimental diet, in which 60% of the milk was replaced by fish meal and wheat. Both diets were given as sole feed under practical feeding conditions. The experimental diet produced a weight increase of 81,9% relative to that of the milk diet; milk consumption was 53.7% the required amount of dry matter 117.4%, milk consumption per kg of weight gain 61.5% and expenditure on feed per kg of weight gain 78%. The general growth development of the piglets was quite good irrespective of the different rates of weight increase. The weight gains after 30 days were 6.6 kg+/-1.5 kg for the experimental diet and 7.0 kg+/-1.2 kg for the milk diet. Losses among the piglets amounted to 0.7% and 2.9%. On the basis of the results of the present trial and of previous experiments the authors believe that under practical conditions of feeding 50% of the milk contained in a liquid milk diet fed to piglets that are 12 to 30 days of age could be replaced by wheat and fish meal.


Growth, purification and characterization of Semliki Forest virus in Ehrlich ascites tumor cell suspensions. The growth of Semliki Forest Virus (SFV) in suspension cultures of Ehrlich Ascites (EA) cells and its purification is described. Large volumes of virus material were concentrated by filtration with DIAFLO XM-300 membrane and precipitation with ammonium sulfate. A combination of protamine sulfate treatment, centrifugation of the virus onto a 50 per cent sucrose cushion, and sedimentation through a 5--30 per cent sucrose density gradient was employed. The purified virus particles were homogeneous as revealed by electron microscopy, by moving boundary electrophoresis, and by polyacrylamide gel electrophoresis. Virus suspensions containing 1 mg/ml of protein had a hemagglutinin titer of 1:12,000 when measured with 0.25 per cent goose red blood cells.


The role of the Tasmanian devil in the epizootiology of ovine cysticercosis and echinococcosis. Tasmanian devils were fed infective cystic material of Taenia ovis, T. hydatigena and Echinococcus granulosus and later killed and examined for adult tapeworms. No infections with T. ovis were found after feeding 23 cysts to 8 devils. T. hydatigena were recovered from 5 to 41 devils and 10 worms established after feeding 417 cysticerci. No E. granulosus were recovered from any of 3 devils. Specimens of T. hydatigena appeared to develop as well in devils as in dogs. From these and previous results devils could be successful hosts to T. hydatigena and T. ovis. A survey of 320 devils failed to detect any natural infections with any of these 3 species.


Purification and some properties of a medium-chain acyl-thioester hydrolase from lactating-rabbit mammary gland which terminates chain elongation in fatty acid synthesis. 1. An acyl-thioester hydrolase was isolated from the cytosol of lactating-rabbit mammary gland. The purified enzyme terminates fatty acid synthesis at medium-chain (C8:0-C12:0) acids when it is incubated with fatty acid synthetase and rate-limiting concentrations of malonyl-CoA. These acids are characteristic products of the lactating gland. 2. The mol.wt. of the enzyme is 29000+/-500 (mean+/-S.D. of three independent preparations), as estimated by polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. 3. The enzyme also hydrolyses acyl-CoA esters of chain lengths C10:0-C16:0 when these are used as model substrates. The greatest activity was towards dodecanoyl-CoA, and the three preparations had specific activities of 305, 1130 and 2010 nmol of dodecanoyl-CoA hydrolysed/min per mg of protein when 56muM substrate was used. 4. The way in which this enzyme controls the synthesis of medium-chain fatty acids by fatty acid synthetase is briefly discussed.


Administration of peripheral-blood rat-lymphocytes stimulated "in vitro" with human lymphokines and spleen colonies in the total body irradiated rat. It was previously reported that PHA-incubation of a pool of peripheral-blood lymphocytes before their i.v. injection into rats submitted to total body irradiation, stimulates spleen colony formation and growth. On the same model, the present study has investigated the effect of lymphocyte preincubation with supernates obtained in short term cultures from human lymphocytes prestimulated with PHA (lymphokines). The "in vitro" culture of rat lymphocytes in a medium supplemented with human lymphokines showed either a marked increase of lymphocyte survival rate, or significant stimulation of lymphocyte blastogenesis, but at an extent much lower than that caused by PHA, also because in this particular experiment the culture medium was supplemented with too little amount of lymphokines. These data support the interpretation that human lymphokines may act across the species barriers. Peripheral-blood rat lymphocytes prestimulated with human lymphokines, and then injected i.v. into rats previously submitted to total body irradiation, caused significant increase in the spleen weight, as well as formation of spleen colonies quite larger and with higher erythroid differentiation - though less numerous than in the controls (i.e., in the rats injected just with untreated lymphocytes). This behaviour may be due to the tendency to merge together of two or more colonies in a single giant colony, and supports the interpretation that immune-competent lymphocytes activated either with PHA or with lymphokines may stimulate spleen colony growth and erythroid differentiation, though at different extents.


Effect of halothane and diethyl ether on the circulatory response to carbon dioxide in the isolated perfused cat lung. Constant flow perfusion of the pulmonary circulation was established in isolated cat lungs. These were ventilated with 5% carbon dioxide in oxygen in order to maintain a near-normal carbon dioxide tension and acid-base status in the perfusing blood. The alteration of pulmonary vascular resistance in response to a change in inspired carbon dioxide concentration from 5% to 10% was investigated before, during and after the administration of 1% halothane (in 16 perfusions) or 5% diethyl ether (in 8 perfusions). An increase of inspired carbon dioxide concentration caused a significant increase in pulmonary vascular resistance, but the magnitude of the increase was diminished during the administration of both anaesthetic agents. The response increased again after the anaesthetics were withdrawn. The administration of halothane during ventilation with 5% carbon dioxide caused a significant reduction of pulmonary vascular resistance whilst diethyl ether resulted in a significant increase in this measurement. It is suggested that inhalation anaesthetic agents may increase ventilation/perfusion mismatching by altering the normal vasoconstrictor response to increased alveolar PCO2;


The effect of narcotic and narcotic-antagonist drugs in the newborn rabbit. The newborn rabbit responds to acute anoxia, as a result of breathing nitrogen, with successive periods of dyspnoea, primary apnoea, gasping and terminal apnoea. Pethidine caused an increase in the period of primary apnoea and a decrease in the duration and rate of gasping. When nalorphine was combined with pethidine the period of primary apnoea was still increased although the duration and number of gasps were restored to control values. Naloxone, in contrast, acted as a mild respiratory stimulant, shown as a longer phase of dyspnoea. Also it completely abolished the respiratory depression produced by pethidine. Naloxone may be preferable to nalorphine as a drug to reverse the effects of pethidine immediately after birth.


Kinetics of inhibition of acetylcholinesterase by spin labeled acetylcholine analogs. A series of spin labeled acetycholine analogs, in which the number of methylene groups between the quaternary nitrogen and the alcohol oxygen ranged between 1-5, have been examined as inhibitors of electric eel acetylcholinesterase. Evidence is presented suggesting that inhibition of acetylocholinesterase by the spin labeled ACH analogs is due to the high affinity of these compounds for the enzyme, inhibition is competitive and reversible. It has been shown that complex formation is of major importance in the reaction between spin labeled ACH analogs and acetylcholinesterase. The acetylation step has been shown to occur by demonstrating that the leaving group is released as the reaction proceeds. Complex formation has been demonstrated by means of kinetic criteria. Kinetic parameter have been measured for the five compounds, and correlations with alkaline hydrolysis are disussed.


[Atherosclerosis in rabbits induced by prolonged electrical stimulation of the hypothalamus]. The influence of prolonged electrical stimulation of rabbit hypothalamus on blood lipids and the development of atherosclerosis were studied. The negative emotional state observed during the electrical stimulation was accompanied by blood hyperlipemia and atherosclerosis development in 1/3 noncastrated and 2/3 castrated animals.


[Effect of aflatoxin B1 in vitro and in vivo]. The direct and transplacental action of aflatoxin B1 was studied on organic cultures of the embryonic pulmonary tissue of mice of the A line, BD-IX rats and golden hamsters (Cricetus auratus W.). Its toxic action on the cultures and the absence of any blastomogenic effect was demonstrated. In experiments on mice the transplacental penetration of aflatoxin B1 led to an increase in the incidence of the breast tumours in the progeny.


[Duration of the mitotic cycle of Chinese hamster cells cultured at 30--39 degrees]. The duration of the mitotic cycle (T) at temperatures of 30, 33, 36 and 39 degrees C was studied in subline 237 of Chinese hamster cells with the aid of the radioautographic method. T was the least at 39 degrees C and increased with reduction of the cultivation temperature. At the temperature range of 33--39 degrees C prolongation of T and its periods was "proportional" to the temperature under study. The characteristic curve gradient of T dependence on the temperature showed a sharp change in the direction of greater figures with the temperature reduction from 33 to 30 degrees C. Analysis of the results of other studies on T duration of the human amniotic cells demonstrated that such sharp elevation of the duration of the mitotic cycle occurred with the change from 39 to 40--41 degrees C. The G1 period was the most and G2--THE LEAST Sensitive to changes of the cultivation temperature.


[Comparative characteristics of compensatory renal hypertrophy following unilateral nephrectomy in mature and old rats]. One of the kidneys was removed in rats from 35 to 900 g in weight; they were then sacrificed 2, 14, 30 and 60 days after the operation. The degree of compensatory hypertrophy of the remaining kidney varied greatly in rats of different age, without decreasing in old age, however. Sixty days after the operation the weight of the hypertrophic kidney in old rats was equal to 55--93% of the weight of both kidneys in control. Hypertrophy of the kidney at any age was accompanied by an increased proliferation of the tubular cells, particularly in their proximal portion. An increase in the size of renal bodies during kidney hypertrophy was characteristic of rats of any age. However, with the advance of age this process developed more rapidly and was stronger. At any periods of investigation the hypertrophic kidney in rats of any age contained a greater number (1 1/2--2 times more) of "open" renal bodies in comparison with the kidney of intact rats.


[Irreversible character of the antimitotic effect of actinomycin D on the egg of Artemia, in the early stages of cleavage]. Inhibition of cleavage by actinomycine D is irreversible. Discussion of the results gives new arguments in favour of a protein synthesis during G2. Necessary for the initiation of the following cell division.


[Effects of amniotic fluid on the development of neoplastic tissue in organotypic culture]. In previous researches, it has been observed that the human amniotic fluid presents in vitro an antineoplasic action. 75% of the examined amniotic fluids contain an anti HCG principle. In order to evaluate if the effect of amniotic fluid is due to this principle, cultures of tumoral tissue have been performed, with the Wolff and Wolff's method, using media containing either positive amniotic fluid or negative amniotic fluid. Results obtained with positive amniotic fluid have confirmed the previous observations. A complete degeneration of both tumoral tissue and mesonephros was observed when the culture medium was enriched with negative amniotic fluid.


Division of the external urethral sphincter in the neuropathic bladder: a twenty years' review. It is now twenty years since the authors first performed division of the external sphincter region in the treatment of the neuropathic bladder. Although a ten year report was published in 1967, it was decided to review all the patients at the end of the twenty year period. The rationale of the operation in the upper motor neurone lesion has been confirmed by modern investigative techniques, while it appears from recent work that the success of the procedure in the lower motor neurone case is due to division of plain muscle which is subjected to excessive sympathetic stimulation. It is the authors' firm conviction that long term catheterization, whether permanent or intermittent is a confession of failure and can be avoided in the vast majority of patients. The operation has proved of permanent benefit especially with the regard to the elimination of residual urine. Further, hydronephrosis, and renal infection and failure, are also benefited in many cases. These factors are of great importance in a condition in which late morbidity and mortality has been usually due to renal causes.


Anterior detrusor tube repair for urinary incontinence in children. The technique, complications and results of an anterior detrusor tube repair for urinary incontinence in children is described. It appears that this procedure is appropriate only for selected cases of urinary incontinence but that it is an operation which should be within the paediatric urologist's repertoire. It is simple to perform, but care should be taken, by omental packing, to prevent a sharp posterior lip to the newly formed bladder neck.


Natural occurrence of an inhibitor of mammalian cell growth in human and mouse cells of normal and tumor origin. N6-(delta2-isopentenyl)adenosine was found both as a component of tRNA and as the cytoplasmic mononucleotide in human leukemic lymphoblasts and myeloblasts from peripheral blood and bone marrow samples. This hypermodified nucleotide was also found in the tRNA and as a mononucleotide in human (MRC-5 and KB) and mouse (A9, FLV, LM, and RAG) cell lines. The relative amounts of this hypermodified nucleotide in the tRNA of the cell lines and the human leukemias were similar (the mean value being 0.06 +/- 0.03 mole % of the total tRNA nucleotide content); whereas the amounts occurring as the free cytoplasmic mononucleotide were more varied but still comparable (the mean value being 0.53 +/- .09 mole % of all cytoplasmic nucleotides) for all cells investigated with the notable exception of all normal, diploid cell lines under study (0.04 mole%). A possible relationship of the free cytoplasmic mononucleotide with the nucleotide in the tRNA for control of mammalian cell protein synthesis in vivo was investigated by addition of N6-(delta2-isopentenyl)adenosine to the culture medium. The exogenously added nucleoside caused inhibition of cell growth within 3 h and cell death within 36 h at concentrations as low as 0.4 muM. No comparable effects were seen when adenosine, adenine, or N6-(delta2-isopentenyl)-adenine were added to the cultures. The simultaneous presence of adenosine in cultures containing N6-(delta2-isopentenyl)adenosine did not alter the detrimental effects of the hypermodified nucleoside on cell growth even when the concentration of adenosine was 50-fold that of N6-(delta2-isopentenyl)adenosine. Addition of N6-(delta2-isopentenyl)adenosine to cell cultures caused within the first 6 h a significant reduction in the rates of RNA and protein synthesis; whereas DNA synthesis continued at a rate comparable to control and adenosine-treated cells for 18 h before decreasing.


Hydrocortisone inhibits the spontaneous detachment of viable mammary tumor cells from monolayer cultures. Primary mammary adenocarcinomas of C3H mice were dissociated to single cells. These cells were seeded at a density of 5 x 10(5)/cm2 substrate area and were grown as monolayers for 36 days in high-serum medium supplemented with insulin. Cultures became confluent within a few days and confluence was maintained throughout the culture period. Viable cells (representing amitotic cell population) were released spontaneously from the confluent monolayer and could be harvested from the culture fluid. The rate of cell release declined after about 30 days, apparently due to mitotic pool depletion. Release of cells from the monolayer was strongly depressed in medium containing hydrocortisone. The cell release event and its alteration by hydrocortisone can be interpreted as reflecting the propensity towards shedding of cells from these tumors in vivo and the alteration of metastatic incidence by adrenal steroids.


Presence of cellular rentinol and retinoic acid binding proteins in experimental rumors. Cellular retinol and retinoic acid binding proteins were detected in mouse skin papillomas, human adenocarcinoma HAD-1, Dunning Leukemia, Walker 256 carcinosarcoma and mammary adenocarcinoma MAC-1. A chondrosarcoma and Sarcoma 180 apparently contain only the cellular retinoic acid binding protein. Neither protein could be detected in Ehrlich carcinoma and L1210 leukemia. The presence of these proteins might be necessary for sensitivity to retinoid therapy.


Excision of epithelial tumors: CO2 laser versus conventional methods. In a comparative experimental study, excisions of a transplanted Lewis lung carcinoma in BDF1 mice were performed by means of the CO2 laser and conventional methods, namely common scalpel and diathermy. The results showed a significant reduction in tumor recurrence and animal mortality rates (27.5% vs. 75% and 45%) after tumor excision with the laser in the early stage (5th day) of tumor development. This finding, in addition to the surgical properties of the CO2 laser, suggests that early excision using this modality is a rational treatment of this type of tumor.


Common metabolites of N-nitroso-2,6-dimethylomorpholine and N-nitroso-bis(2-oxopropyl)amine in the Syrian hamster. N-Nitroso-2,6-demethylmorpholine (NDMM) administered intraperitoneally to Syrian hamsters was metabolized  to N-nitroso-bis(2-hydroxypropy)(2-oxopropyl)amine(HPOP) and N-nitroso-bis(2-hydroxpropyl)amine (BHP) which were identified in blood and urine. The potent pancreatic carcinogen N-nitroso-bis(2-oxoproply)amine was previously shown to form the same metabolites. Preliminary results indicate that NDMM also induces pancreatic and other tumors in Syrian hamsters, similar to those found following BHP treatment.


Phase I alternate-day dose study of chromomycin A3. Chromomycin A3 was given to 43 patients with metastatic cancer in order to determine the tolerable dose when the drug was administered on an every-other-day dose schedule for a total of five iv push injections, with the course of therapy being repeated every 4 weeks. At least three patients were entered at each dose level, graduated in 0.1-mg/m2 increments between 0.7 and 1.6 mg/m2. The most common (19 patients) side effect was nausea and/or vomiting, but this was usually mild, lasted for a few hours, and diminished in severity with repeated injections. Skin necrosis due to drug extravasation was a problem early in the study, but was eliminated by injecting the drug through iv tubing. Transient elevations in SGOT and alkaline phosphatase levels were observed, but proved not to be of serious consequence. Renal toxicity proved to be the limiting factor in therapy. However, a dose level of 1.3 mg/m2 was found to be a tolerable level of drug administration in previously untreated patients. Objective tumor responses were noted in four patients (Hodgkin's disease, embryonal rhabdomyosarcoma, adenocarcinoma of the lung, and malignant melanoma).


Studies with 2,5-piperazinedione, 3,6-bis(5-chloro-2-piperidyl)-,dihydrochloride. I. Cell kinetic and biologic effects in cultured L1210, human epidermoid No. 2, and adenocarcinoma 755 cells. Experimental results obtained with cultured L1210, human epidermoid No. 2, and Adenocarcinoma 755 cells are consistent in showing that inhibition of proliferation of the cells by 2,5-piperazinedione, 3,6-bis(5-chloro-2-piperidyl)-,dihydrochloride is accompanied by cell enlargement. Although cells initially in the G2 phase when exposure to the agent is begun can probably proceed through mitosis and divide, cells that are initially in G1 and S phases accumulate in the G2 phase. Progression of cells to G2 phase during the period of exposure to the agent is not a requisite for cell-killing, because cells exposed for periods insufficient to permit their accumulation in G2 are killed.


Structural studies on the extracellular polysaccharide of the red alga, Porhyridium. Partial acid hydrolyzates of the extracellular polysaccharide from Porphyridium cruentum yield three disaccharides and two uronic acids. These constitute all of the uronic acid in the polymer. The novel disaccharides are 3-O(alpha-D-glucopyranosyluronic acid)-L-galactose, 3-O-(2-O-methyl-alpha-D-glucopyranosyluronic acid)-D-galactose, and 3-O-(2-O-methly-alpha-D-glucopyranosyluronic acid)-D-glucose. The polyanion of high molecular weight contains D- and L-galactose, xylose, D-glucose, D-glucuronic acid and 2-O-methyl-D-glucuronic acid, and sulfate in molar ratio (relative to D-glucose) of 2.12:2.42:1.00:1.22:2.61. Preliminary periodate-oxidation studies suggest that the hexose and uronic acids are joined to other residues by (1 leads to 3) glycosidic linkages. About one-half of the xylose residues are (1 leads to 3)-linked.


Microinjection studies of duck globin messenger RNA translation in human and avian cells. Microinjection techniques were used for the study of the translation of heterospecific messenger RNAs in living cells. Duck globin messenger RNAs, in the form of polysomes, messenger ribonucleoprotein particles, or free mRNAs, were injected into cells of human origin (HeLa), and the subsequent appearance and accumulation of avian globin were measured by specific immunofluorescence techniques. Globin accumulated within a high proportion of HeLa cells for at least 25 hr following injection, indicating the intracellular stability of the heterospecific globin messenger RNA and the fact that mRNA initially associated with more complex structures could be translated in the HeLa cytoplasm. In similar experiments, duck reticulocyte polysomes were shown to be translated in duck embryo cells but not in embryonic chick liver cells. The latter, however, could be shown to withstand the microinjection procedure as judged by their capacity to respond normally to inducers and inhibitors of the synthesis of alpha-aminolevulinic acid synthetase. HeLa cells injected with duck hemoglobin divide at normal or nearly normal rates following the injection, but their globin content diminishes, in contrast with the increasing globin content of cells receiving duck reticulocyte polysomes, mRNP particles, or free mRNA.


The 3' terminal sequences of human alpha and beta globin messenger RNAs: comparison with rabbit globin messenger RNA. Sequences of 43 and 70 nucleotides adjacent to the 3' terminal poly(A) of human alpha and beta globin mRNAs have been established. Sequence analysis of complementary DNA from both normal and thalassemic globin mRNA preparations was carried out using endonuclease IV digestion and limited synthesis procedures. The two RNA sequences are 83% homologous to rabbit globin mRNA (Proudfoot, 1976), and a part of the alpha globin mRNA sequence codes for the carboxy terminus of human alpha globin Constant Spring (Clegg, Weatherall, and Milner, 1971). This latter result predicts that the 3' noncoding region of human alpha globin mRNA is exactly 112 nucleotides, while the 5' noncoding region is probably about 50 nucleotides.


Chromatin organization in nuclei of sea urchin embryos. Comparison with the chromatin organization of the sperm. The chromatin in sea urchin embryo nuclei and that in sperm heads are both organized in nucleosomes but show marked differences when analyzed by endonuclease digestion. Sperm chromatin DNA appears to be totally organized in nucleosomes that are highly resistant to nuclease hydrolysis. The kinetics of formation of acid-soluble oligonucleotides is slow and concerns only about 50% of the total DNA. In contrast, the DNA of embryo chromatin does not appear to be totally organized in nucleosomes since 5 to 10% is rapidly and preferentially hydrolysed into acid-soluble oligonucleotides without any appreciable fragmentation of the remaining parts. Futher digestion causes the formation of the usual pattern of DNA bands, as detected by gel electrophoresis. The length of the DNA segment associated with the embryo nucleosomes appears to be shorter than that of the DNA segment associated with the sperm nucleosomes. The kinetics of formation of acid-soluble oligonucleotides upon digestion of embryo chromatin is much faster than that of sperm chromatin and concerns almost all the chromatin DNA.


Vitamin A acid: clinical investigations with 405 patients. Vitamin A acid (retinoic acid) is less toxic than vitamin A and seems to be an important advance in dermatology. Its therapeutic effect was investigated in clinical studies involving 405 patients. Biochemical investigations have shown that the administration of vitamin A acid is associated with elevation of serum levels of retinol and carotene and after high dosage symptoms develop identical with hypervitaminosis A. Several possibilities regarding the mode of action of vitamin A acid are discussed.


Perioral dermatitis: etiology and treatment. Ninety-five patients with perioral dermatitis were studied from an epidemiological aspect. Consistent clearing of the eruption was obtained with oral tetracycline in combination with a topical sodium sulfacetamide-sulfur-hydro-cortisone lotion. Comparison of the study group of patients to a group of 50 control patients revealed highly significant quantitative differences in the cosmetic preparations used by the two groups. This latter finding would suggest that lubricating and moisturizing products play some part in the etiology of perioral dermatitis.


Prognostic significance of ploidy level in human tumours. II extra-uterine cancers and summary of data on 1171 tumours. The 5-year survival rate of 78 patients with carcinoma of the ovary showed that the prognosis was significantly better when the tumour modal DNA value was in the diploid region than when it was near-triploid or above. Similar data on 140 patients with carcinoma of the breast and 52 with carcinoma of the bladder also suggested a better prognosis for the near-diploid tumours. Among 105 carcinomas of the large bowel, however, there were more survivors in the high-ploidy than in the near-diploid group, although the difference was not statistically significant. The varying relationship between ploidy and prognosis, depending on the site or histological type of the tumour, is briefly discussed on the basis of the 1171 cases included in the present and a previous paper.