Changes in pulmonary function in workers exposed to vinyl chloride and polyvinyl chloride. To determine whether occupational exposure to vinyl chloride gas and polyvinyl chloride dust is associated with changes in pulmonary function, spirometry and maximum expiratory flow-volume curves were obtained in 348 workers in a VC polymerization plant. The major finding was diminution in air flow in 200 workers (57.5 percent). This abnormality correlated with age and duration of exposure. A relationship with smoking was noted only in younger workers with exposures of less than 10 years. When age exceeded 40 years or exposure 20 years, prevalence of this impairment was similar in smokers and nonsmokers, suggesting that occupational or other environmental factors were operative.


Liver disease among polyvinyl chloride production workers. A protocol for systematic testing of all employees of a chemical plant is presented. This factory manufactures polyvinyl chloride compounds and resins, ABS compounds and resins, and synthetic rubber. The results were reviewed, which led to the discovery of 2 additional cases of angiosarcoma and 11 cases of portal fibrosis. Two of the 11 cases were found to have developed in employees other than polyvinyl chloride production workers.


A method of localisation and fixation for mid-facial osteotomies. A preliminary report on a method of localisation and fixation for mid-facial osteotomies is described. The method depends on the localisation of the mandible in a predetermined open-mouth position, so allowing surgery to be performed with an oral tube. The method offers advantages in terms of surgical safety and accuracy. It is theoretically applicable to a wider range of osteotomies than the Le Fort II procedure described here.


The indications for the transplantation of maxillary canines in the light of 100 cases. One hundred cases of autogenous transplantation of maxillary canines are reviewed and the results assessed. They were divided into Group A, 50 cases 3 to 10 years out of retention, and Froup B, 50 consecutive cases 1 to 3 years out of retention. If the criteria for success depended on a normal response to vitality test, 62 per cent of Group A and 24 per cent of Group B were successful. If a prognosis rating was used, 68 per cent of Group A and 72 per cent of Group B had a good prognosis.


Rheumatoid arthritis of the temporomandibular joint. An investigation into the involvement of the temporomandibular joint in rheumatoid arthritis is described. There is evidence to show that is is affected in two-thirds of all cases of the disease, and this figure agrees broadly with other recent studies. The clinical and radiographic presentation is discussed and its relationship to degenerative disease (osteoarthosis) of the temporomandibular joint is shown. The clinical course of this manifestation of rheumatoid arthritis is proposed and a line of treatment is suggested.


Jaundice following oral surgery: Gilberts syndrome. Jaundice developed in two patients following dental operations under general anaesthesia. Gilbert's Syndrome was established as the diagnosis. Caloric deprivation at the time of surgery resulted in the increased plasma concentration of unconjugated bilirubin. The pathogenesis of this not uncommon disorder and the mechanism of fasting hyperbilirubinaemia is discussed.


Tetrahydrofolic acid: an inhibitor of the methyltetrahydrofolic acid-mediated methylation of indolethylamines. Tetrahydrofolic acid exerts a product inhibition on the methyltetrahydrofolic acid-mediated methylation of indolethylamines. Kinetic studies showed that this inhibition was competitive with respect to methyltetrahydrofolic acid and non-competitive with respect to N-methylserotonin. Chromatographic separation of S-adenosylmethionine-dependent indolethylamine N-methyltransferase and methyltetrahydrofolic acid-dependent methyltransferase from rabbit lung was obtained. There was no cross reaction of the two enzymes to tetrahydrofolic acid, S-adenosylhomocysteine, N, N-dimethyltryptamine or bufotenin.


Removal of abnormal clone of leukaemic cells by splenectomy. A patient with chronic myelocytic leukaemia positive for the Philadelphia (Ph-1) chromosome underwent splenectomy in the "terminal phase" of his disease. Chromosomal analysis of a marrow aspirate obtained during the operation showed nothing abnormal. Material from the spleen, however, showed the absence of a C chromosome and the presence of a "marker" chromosome in all metaphases examined. The patient did well for almost three years after splenectomy, and serial cytogenetic studies of marrow specimens showed the Ph-1 chromosome to be the only significant abnormality. Six months before death from recurrent blastic transformation aneuploidy was found in a marrow specimen. Subsequently additional abnormalities, including cells with two Ph-1 chromosomes, were detected. The karyotypic abnormalities found in the splenic specimen, however, never recurred.


Granulocytic sarcoma of the orbit. Report of a case. A 14-year-old youth had a 2 month history of proptosis of the left eye when he developed pain in the left thigh. Physical examination revealed a mass involving the left orbit and a neurologic deficit suggestive of involvement of the left lumbosacral plexus. The mass, a left frontal epidural tumor, was removed surgically. Subsequently, he developed marked anemia, thrombocytopenia, and acute granulocytic leukemia. He was treated with various anticancer agents but he did not respond well and he expired two months later. Postmortem examination revealed anaplatic granulocytic cells infiltrating numerous tissues including the conjunctiva, choroid, and leptomeninges. Marked degenerative changes of the left retina and bilateral papilledema were evident.


A resistometric study of order-hardening in dental gold alloys. The ordering process in gold-copper-silver dental alloys was studied by means of isochoronal and isothermal resistivity measurement. Because the stable existing temperature range of orthorhombic superlattice was unexpectedly extended to lower temperature by the addition of silver to gold-copper binary alloy, the ordering velocity in these alloys are considerably slower than that of binary stoichiometric AuCu alloy. Activation energy, the order of the reaction, and rate constant for growing process were established. The difference in growing mechanisms depending on gold concentration was deduced from the kinetics data.


Abnormalities of the sciatic nerves of dystrophic mice, with reference to nerve counts and mean area of axons. Ultrastructural changes of the sciatic nerves of c58bl/6j-dydy mice were examined. Nerve counts were calculated and the area of axons was measured in these nerve tissue. Many large bundles of unmyelinated nerves were observed at the proximal portion of the sciatic nerve without cytoplasm or basement membrane of the Schwann cell. These bundles were composed of axons of various sizes and shapes, including some vary large axons. The large unmyelinated axons decreased in number and size as nerves descended to the distal portion. The myelinated nerves showed irregular shapes. Some myelinated nerves were enveloped in very thin myelin sheaths for the mouse age. The destructed myelin was often observed from the radix to the  distal portion of sciatic nerves. They lost their myelin sheaths at the Ranvier node, and descended for long  distances with naked axons. The neighboring myelin segments of naken axons showed unusually bizarre shapes. They seemed to be the abnormal development of the demyelinated axons. Such findings were very similar to those of the embryonal developing peripheral nerves.  It was concluded that the muscular dystrophy of the C57BL/6J-dydy mice might be related to dysmyelination and to the decrease in the number of myelinated nerves.


Epidermoid tumor in the lateral ventricle. Significance of echo-encephalography. The authors report on a case of epidermoid tumor in the lateral cerebral ventricle. Epidermoid tumors are relatively uncommon intracranial lesions and were first described by Esmarch. Till now about 300 cases have been reported. In Japan this tumor was first described by Yamamura, and since then many cases have been reported. But the one situated in the lateral ventricle has not been reported yet in this country. The significance of echo-encephalography is discussed because this procedure was very useful in determining the location and the nature of the tumor of this case.


Findings with swan-type double-bending gastrofiberscope. By using the swan-type double-bending gastrofiberscope, it has become very easy to observe such regions as the cardia, posterior wall of the upper corpus or the pyloric region. The authors can obtain a clear image of the cardia, especially the form of the fold of the region or the esophagogastric junction. The authors recognized that the form changes according to the amount of the inflated air, and the insufficient function of the cardia can be easily diagnosed. The degree and form of the elevation of the posterior wall of the upper corpus of the stomach was observed and classified into three types, flat type, slightly elevated type and highly elevated type. Pathological deformation of this region was studied from the shape of this elevation. By the close observation of the pyloric region, it was clarified that the appearance of the folds may be radiated, transverse at the lesser curvature or entirely lost, being closely related to the presence of the erosions in this region. The healing process of the gastric ulcer was examined endoscopically from the viewpoint of the radiating vessel zone and contraction by the scar. When the capillary vessels are the more prominent finding of a healing ulcer, it tends to form a surface possessing a scar after it is healed and when the contraction is more prominent, it tends to form a linear scar after healing. By the recrudescence of the gastric ulcer, the irregular capillary vessels or deviation of the convergence of the folds are observed, and by the recurrence of the ulcer, coexistence or completion of a scar is observed.


On half-clearance time of carbon monoxide hemoglobin in blood during hyperbaric oxygen therapy (OHP). The elimination rate of COHb in the blood was measured by a tonometer and the COHb  saturation of the human blood under the exposure of 0.3% CO in the air for 30 minutes was estimated to be about 47%. The CO elimination of the tonometered blood by the exposure to 4 kinds of gases, 1 ATA air, 1 ATA O2, 1.9 ATA O2 and 2.8 ATA O2 showed a linear decrease on the semi-logarithmic figure, and the gradient coefficient (k) of the straight lines showed a good reproducibility and significant difference from each other. The COHb elimination after suppluing a 0.3% CO air mixture for 20 minutes to 23 mongrel male dogs weighing 12 to 18 kg were observed by letting them breathe 1 ATA air for 300 minutes, 1 ATA O2 for 120 minutes, 1.9 ATA O2 for 60 minutes and 2.8 ATA O2 for 30 minutes. The COHb decrease of the CO-poisoned dogs showed also a semi-logarithmically linear tendency and the gradient coefficient (k) among these four gas-breathing groups showed a significant difference. The mean half-clearance time (t/2) of each group was: 1 ATA air for 188 minutes, 1 ATA O2 for 32 minutes, 1.9 ATA O2 for 25 minutes and 2.8 ATA O2 for 12 minutes. The higher the O2 partial pressure in the inspired gas increased, the greater became the decrease of the COHb clearance time and the greater became the reducting of the half-clearance time. The CO elimination by the dogs at high PO2 on the contrary, an opposite relation was observed. This fact may be explained by the improvement of the ventilatory and circulatory functions of the alveloi concerned with the CO elimination at a high PO2 but at a low PO2 the alveolar functions are impaired by CO and the O2 supply is insufficient to cover the dysfunction, so the CO elimination is larger in the tonometered blood than in the dog blood. The procedure of OHP for CO poisoning was designed by the CO elimination rate in the dog, assuming it to be the same as that in the human, for the patients of three levels of severity fo CO poisoning: phase I is breathing of 2.8 ATA O2 for 20 minutes, usually for the patients of each level of severity, then Phase II (breathing of 1.9 ATA O2) follows after that for severe poisoning (COHb in the blood, 80%) for 57 minutes, for medium poisoning (COHb, 60%) for 46 minutes and for light poisoning (COHb, 40%) for 32 minutes. After the treatment of Phase II, the blood COHb content decreases to 5%, a safety level for CO poisoning. This process is practical and effective for the OHP treatment of CO poisoning, and besides it is not only safe against O2 poisoning but also is capable of supplying rapidly sufficient amount of oxygen to improve the condition of the anoxic tissues.


Physiological reaction of men under excercise to radiant heat. To investigate the effect of the radiant heat on the human body in a hot environment, the subjects exposed their nude back to a radiant heat of 1.3 and 2.6 cal/cm-2. min, using the exsiccating infrared illuminators under a hot ambient condition of a temperature 31 degrees C, with a relative humidity of 55% and a 0.5 m/sec air flow. The 8 subjects were healthy male college students aged 20 to 25. The following results were obtained by estimating the physiological reactions to different degrees of radiant heat at rest for 60 minutes and during exercise for 30 minutes on a bicycle ergometer by 272 kg. m/min (or 600 kp. m/min). 1) The mean skin temperature, heart rate, respiration rate and body weight loss rate increased at rest in parallel with the degree of the radiant heat, and during exercise the mean skin temperature, heart rate, respiration rate, body weight loss rate and respiratory volume increased, but the NA+ LOSS RATE DECREASED. The regression equation was obtained to show the quantitative relationship between the degree of the radiant heat and the physiological body reactions. 2) By computing the Heat Tolerance Index by Inoue et al., it was clarified that the higher the degree of the radiant heat was, the smaller was the index. And as there was a close correlation between the indices both at rest and during exercise, it was suggested that for the evaluation of heat tolerance, the radiant heat by the infrared illuminators is applicable as additional heat loading besides hot water bathing or staying in a hot chamber.


Renal microvasculature in acute renal failure. The ranal microvasculature evidenced by intraarterial injection of silicone rubber performed in 10 cases of acute renal failure from various causes demonstrated definite reduction in filling with patchy deficit in subcapsular cortex, narrowing of preglomerular arterioles, especially at the branching from the interlobular arteries in the same area, relative increase in filling of vas afferens and efferens of juxtamedullary cortex, and of vasa recta in medulla. The same injection figures are observed in acute renal failure in dogs experimentally induced by ligation and clamping of renal arteries, and intraarterial infusion of large quantities of angiotensin II (1000 ng/kg/min). Although the etiological factors of acute renal failure are manifold and the parenchymal damage is varied as well, the vasoconstriction of preglomerular arterioles should be considered as an initial common pathway which continues in subcapsular cortex. The result of present  experiments is consistent with the hypothesis that renin and angiotensin participate in the pathogenesis of acute renal failure.


Growth and hormone control mechanisms in osteosarcoma. Evidence for a new therapeutic approach. The association between osteosarcoma and growth, including altered carbohydrate metabolism has been investigated in 5 osteosarcoma patients. Serum from an adolescent osteosarcoma patient has been noted to consistently enhance 3-H-thymidine uptake in cultured chondrocytes and tumor cells. Females survive osteosarcoma more frequently than males. In vitro serum-enhanced proliferation of osteosarcoma cells is suppressed by estradiol.


In vitro "education" on autologous human sarcoma generates non-specific killer cells. The cytotoxic effects mediated by lymphocytes from cancer patients after in vitro "education" on autologous tumor cells have been investigated. Peripheral blood lymphocytes from three sarcoma patients were cultivated on autologous tumor-cell monolayers and tested thereafter in a micro-cytotoxicity assay against tumor and fibroblast cells. This procedure led to the progeny of non-specific killer cells. As the phenomenon did not occur when the same lymphocytes were co-cultivated with autologous fibroblasts, the generation of non-specific effector cells may have been caused by specific antigenic triggering. The presence of autologous serum during "education" was found to inhibit the manifestation and/or the generation of killer cells. The same serum was without effect when added during the cytotoxicity assay only.


Projections of the dorsal column nuclei and the spinal cord on the inferior olive in the cat. This study demonstrated partially overlapping fiber termination areas in the inferior olive originating from the dorsal column nuclei and the spinal cord. Based on the distribution of the dorsal accessory olive can be divided into a rostral and a caudal part. In the caudal part terminations are found of fibers originating in the contralateral gracile nucleus and in the lumbar and cervical spinal cord. Terminations in the rostro-medial part of the dorsal accessory olive arise from the contralateral internal cuneate nucleus and from the opposite intermediate grey at C.1. Fibers from more caudal regions of the internal cuneate nucleus terminate in the dorsal accessory olive caudal to those originating from more rostral regions of this nucleus. The gracile nucleus and the lumbar spinal cord project to the rostro-lateral portion of the dorsal accessory olive. The terminations in the medial accessory olive from the lumbar spino-olivary fibers are found in a laterally located zone in the caudal half of the medial accessory olive, while terminations of the contralateral internal cuneate nucleus are found at a more rostral level in the medial part of the medial accessory olive. Connections between the inferior olive and the caudal part of the spinal trigeminal nucleus, the lateral cervical nucleus and the cervical dorsal horn could not be demonstrated.


Clinical situations in which amputation is preferred to pulp capping because of biologic considerations. Calcium hydroxide, in its various forms, has become the preferred agent of most practitioners who perform pulp capping. The application of calcium hydroxide to the pulp stimulates the growth of new dentin and protects the pulp from subsequent irritation. However, the new dentin generated by the pulp may, in turn, infringe on the pulp. If the thickness of the pulp tissue is large, this infringement will not be significant. If the volume of pulp tissue is shallow, the same amount of infringement may cause sufficient impairment of circulation to the cornal area of the pulp, leading to an area of the necrosis may then contaminate the entire pulp, and root canal therapy will become necessary. Therefore, pulpal amputation is the preferred treatment in such situations.


An evaluation of an electroanesthetic device. An electroanesthetic device exported from the Soviet Union was tested for its usefulness in controlling pain during tooth cutting procedures. Indexes to measure patient anxiety levels and predicted pain perception were designed, and their validity was tested. For the study, 170 patients were separated into subgroups who knew that an electroanesthetic device was being tested and those who did not. Results showed a greater pain reduction for those procedures that usually elict high pain levels and little benefit of anesthesia for procedures with low pain levels. The responses of the subgroup of persons who know the purpose of the device were higher than average for all pain levels.


Chronic MPD, group therapy and psychodynamics. Three groups of patients with myofascial pain-dysfunction syndrome received 12 eclectic group psychotherapy sessions. The principal reason for selecting this mode of treatment was to observe the group dynamics for the operation of intra and interpersonal variables that might support the psychophysiologic hypothesis for myofascial pain-dysfunction syndrome and validate the existence of personality characteristics that are associated with patients who have myofascial pain-dysfunction.


Kinesiometric instrumentation: a new technology. A method of monitoring mandibular movements in three dimensions is described whereby a premanent magnet is secured to the mandible, and magnetometers are located relative to the permanent magnet so as to sense changes in the magnetic field which result from mandibular movement. The outputs of the magnetometers are processed electronically to obtain three discrete analog voltages, each directly proportional to a specific distance--vertical, anteroposterior, or lateral--from the magnet to the particular magnetometer. The verticle distance output is differentiated electronically to provide a measurement of acceleration. The Mandibular Kinesiograph provides new capabilities for diagnosis and research in dentistry.


Effects of force direction on supporting bone during tooth movement. Photoelastic stress analysis by means of simulated load application on model structures was used to visualize the forces that are induced within the supporting bone structures during various tooth movements. A comprehensive picture of the stress patterns produced by these forces, in addition to the degree of stress distribution, was obtained. The results of this study are relevant to the basic tooth movement procedutes that are used by the clinician in general practice.


Dental relationships in tongue-thrusting children as affected by circumoral myofunctional exercise. Thirty-two children with tongue-thrusting habits and nine nonthrusters participated in this study. Twenty of the tongue-thrusting children exercised their lips twice daily by pulling on a button placed in the labial bestibule. Spring scales recorded the displacing tension on the lips; exercise continued from three to six months. Pre- and postexercise headplate tracings and dental study casts were used for measurement of alterations in tooth position. The tongue-thrusting children exhibited weaker lips initially than did the non-tongue-thrusters. The lip muaculature was strengthened by daily exercise and the improvement remained for 18 months after cessation of the exercies. No signigicant change in incisor protrusion or the open bite was observed throughout the two-year study period. We conclude that increasing the lip muscle strength in tongue-thrusters may have little effect on the dentition of children exhibiting tongue-thrusting.


Orthosurgical teamwork.

Orthosurgical teamwork. A series of orthognathic cases illustrates the potential service that is available to young adult and adult patients. These patients have problems that are not within the therapeutic possibilities of orthodontics alone. From a variety of viewpoints--length of time, appliance wear, iatrogenic damage, and patient concern--such procedures may well be preferred and ultimately more successful and stable than alternate conventional orthodontic therapy. Surgical procedures, in combination with orthodontics and prosthetics, have now achieved a level of sophistication that permits correction of almost any type of facial deformity quickly, with minimum pain, and relatively few unfavorable sequelae.12.13.15.


C3 receptors on lymphoid cells: isolation of active membrane fragments and solubilization of receptor complexes. Complement receptor activity for cell bound C3b and C3d was detected on plasma membrane fragments prepared by nitrogen cavitation from cultured human lymphoid cells. The activity of the membrane fragments reflected the activity of the whole cells in that cells which did not form rosettes (P3J and RPMI 4098) resulted in inactive membranes and cells with high rosette formation (NC37 and Raji) yielded highly active membrane fragments. Two test systems were devised to detect these receptor activities, namely a rosette inhibition and a hemagglutination assay. Solubilization of C3 receptors was accomplished by extraction of active plasma membrane fragments with 2 MKBr. Dissociation and reassociation experiments suggest C3b and C3d receptors to be highly complex molecular structures. It appears that these complement receptors on plasma membranes rely on both protein and lipid moieties for the expression of their activity.


Endoscopic findings of maxillary sinus after middle face fractures. Of 93 patients with fractures of the mid-face who appeared for postoperative check-up, 25 were selected by chance for sinuscopy of the maxillary sinus. Chronic inflammatory mucosal changes occurred in 35 per cent; other pathological sequelae included solitary polyps, mucocele, scarry synechia, and prolapse of orbital fat and osteoma. In spite of these findings, all patients were free of complaints. The primary surgical revision was therefore declined in favour of a waiting attitude. For the diagnostic clarification of late complications, sinuscopy with Hopkin's optics offers a simple and efficient procedure, which should be routinely utilised.


Long-term results of functional treatment of condylar fractures with the long bridle according to A. Rehrmann. Long-term results in 23 cases with condylar fractures are presented. The method of treatment consisted in forward extension of the mandible by means of a long rubber bridle stretched between a steel hook at the chin and a strong sagittal wave-like, bent wire incorporated in a head cap. Strength and direction of the bridle can be modified. It provieds perfect repositioning of the mandible and a normal occlusion within some hours. The idea of this functional method is to eliminate the displacing muscular pull and dorsally-directed deviation of the mandible, and to restore muscular balance even with full range of mouth-opening. The distraction of the mandible from the glenoid fossa creates space and enables the dislocated condyles to upright themselves spontaneously. In cases of intracapsular or subcondylar fracture the active movements of the mandible, under the conditions of equilibrium, lead to a remodelling of the damaged condylar heads to a new form, induced by function. Ankylosis is avoided with certainty. Mandibular splinting or osteosynthesis are needed only in concomitant fractures of the rest of the mandible. The temporo-mandibular joint area and the rest of the mandible are considered to be independant entities in the treatment of condylar fractures. The method described is simple. Full mandibular mobility was obtained in all cases and spontaneous uprighting of dislocated condyles observed. There was no need for subsequent opening exercises.


Construction of the upper lip, columella and orbicularis muscle in bilateral clefts. A concept for repair of double clefts is described. In the primary operations at the age of six months on the first side, and six weeks later on the other, it is important to supply the prolabial mucosa by muscular vermilion flaps from the lateral sides, crossing the midline. Thus a muscular ring in the vermilion is obtained. At the age of 3-4 years both remaining muscular halves of the lip are united. This is achieved togeather with lengthening of the columella, using broadened prolabium to a natural looking philtrum. Lips repaired this way are satisfying with regard to both appearance and function.


Effect of radiation injury on the growing face. The literature on the effect of ionizing radiations on developing and rapidly growing tissue has been reviewed, and the effect especially on children who received radiation therapy in the Clinic for Maxillo-Facial and Plastic Surgery of the University of Dusseldorf for various tumours of the head and neck presented. Our findings indicate that we do not yet know the minimal irradiation dosage that may cause growth retardation in infants and children. It has therefore been suggested that surgery should be more frequently considered in the treatment of childhood tumours, since this caused less side effect, and reconstructive surgery is today able to do much for patients who have had parts of their jaws resected.


On the biological behaviour of basaliomas. On the basis of our experience in 250 clinically and histologically proved cases of basaliomas, these tumours are classified as benign. Facts which seem to argue in favour of malignancy are refuted systematically. The criteria of the nature of carcinomas therefore do not apply to basalioma. Nevertheless the fact should not lead to underestimation of these tumours and to inadequate treatment.


Conservative parotidectomy in infancy and childhood. The indication for operations of benign tumours of the salivary glands in infancy and childhood is taken with great caution and is only partially recommended as the therapy of choice. This applies especially to hemangiomas, since spontaneous retrogression has been observed and there is the danger of damage to the facial nerve during surgery. Knowing unsatisfactory late cases of hemangiomas the author recommends conservative parotidectomy in cases of fast-growing hemangiomas. The anatomic structures in infancy, as well as the lack of pneumatisation of the mastoid process and the fragility of the cartilagineous auditory meatus should be taken into consideration during surgical exploration. The atypical course of the facial nerve in large tumours of the parotid gland is pointed out.


Blood gases, acid-base balance, and serum electrolytes following extensive maxillo-facial surgery. Major maxillo-facial surgery causes arterial hypoxaemia, as well as a depletion of electrolytes serum protein during the postoperative period. Based on the investigations of 25 patients, a repertoire for the study of the postoperative course after major maxillo-facial operations has been offered, and a method for the avoidance of complications suggested.


Diagnostic and therapeutic regime for reducing mortality after resection of tumours in the head and neck. This paper presents the findings made on the rate of mortality following tumour resections in the head and neck achieved in the Clinic for Maxillo-Facial and Plastic Surgery of the Face, University of Dusseldorf, from 1953 to 1973. The relationship between rate of mortality and improved measures taken before, during and after the operation are also discussed.


Concerning asymmetrical growth following repair of cleft lip. Preliminary Report. The results of the measurements of upper lips repaired according to a modified Tennison-technique (which has been previously published (Bick 1961) are presented. Contrary to the measurements done at that time after Le-Mesurier-plasty (1949), the present results did not show asymmetry of the upper lip in any case. This is attributed to the fact that there is no tissue loss in using this modified incision line.


Evaluation and refinement of the intraoral vertical subcondylar osteotomy. Data were collected from the use of intraoral vertical subcondylar osteotomy in 42 patients. The results of treatment compare favorably with those attained with sagittal split osteotomy and extraoral vertical subcondylar osteotomy. Modification in instrumentation and techniques has further improved the intraoral vertical subcondylar osteotomy. The primary advantage of this technique compared to the sagittal split osteotomy is the much less frequent and less severe damage to the mandicular nerve. This intraoral technique deserves serious consideration as the method for reduction of the prognathic mandible.


Postauricular approach for surgery of the temporomandibular articulation. The adaptation of a postauricular approach for surgical exposure of the temporomandibular articulation is presented. The ease, safety, and predictability of extensive exposure have led us to use this approach exclusively for surgical intervention in this region. It has been effectively used in cases of trauma, pathologic conditions, and reconstruction involving the TMJ. In addition to the cases reported in this series, the procedure may be adapted to oblique subcondylar oestotomies and to the treatment of a variety of regional neoplastic processes and other forms of TMJ dysfunctions that may be encountered.


Odontogenic myxofibroma: report of two cases. We have reported the occurrence of two odontogenic mesenchymal tumors of the jaws. Though both cases had an associated impacted tooth, neither had foci of epithelial growth. Results of clinical, radiographic, and histopathological analysis in both cases were consistent with the diagnosis of a fibroma with myxomatous degeneration and thus, the diagnosis was myxofibroma.


Primary Ewing's sarcoma of the mandible: report of case. A case of primary Ewing's sarcoma of the mandible in a 4-year-old Negro boy has been presented. The incidence in this age, site, and race is rare. This previously fatal tumor has been more recently controlled with a combination of radiation therapy and chemotherapy. The patient has responded very favorably with the use of these combined modalities of therapy. After eight months, he is free of symptoms and bone has regenerated in the area of the initial tumor. If detected early, there is hope that this highly malignant disease can be controlled for prolonged periods of time.


Le Forte I osteotomy for correction of maxillary deformities. With proper planning, execution, and follow-up care, the maxilla can be surgically repositioned into a stable relationship with the mandible. Complete mobility, preservation of viability by proper design of the bony and soft tissue incisions, and adequate fixation during the healing phase are essential to obtain this objective. Variable maxillary deformities in 15 adults were corrected by Le Forte I osteotomy techniques. The technical problems in planning and design for the necessary bony and soft tissue incisions are discussed and illustrated by three case reports.


Enflurane anesthesia for oral surgery.

Enflurane anesthesia for oral surgery. Enflurane was administered to 100 unselected patients undergoing various oral surgical procedures. The anesthetic provided smooth induction, maintenance, and rapid recovery. Vital signs remained stable during anesthesia. No ventricular arrhythmias were observed in the presence of exogenous epinephrine used for surgical infiltration. Postanesthesia incidences of nausea, vomiting, and excitement were minimal. Our experience suggests that enflurane may be the preferred anesthetic agent both for minor dental procedures in outpatients as well as for major oral surgical procedures in hospitalized patients.


A study of antibiotic usage in compound mandibular fractures. The need for antibiotic coverage in compound mandibular fractures was tested in 64 patients with fractures in tooth-bearing areas in a study that began in January 1971 and ended in May 1974. Half of the patients received antibiotic coverage as part of the management of their fractures; the other half did not receive antibiotics. Problems related to infection at a fracture site developed in only 6.25% of patients treated with antibiotics. Infections directly associated with fractures developed in 50.33% of patients who did not receive antibiotic coverage.


Postoperative sequelae of cryosurgery.

Postoperative sequelae of cryosurgery. Cryosurgery is a proved method for treatment of neoplasms of the soft and hard tissues of the oral cavity. It is not free, however, from postoperative complications. Delayed healing and extensive scarring are common occurrences. Significant functional and esthetic impairment, although uncommon, can result. Exposure of lingual mandibular bone can interfere with prosthetic replacement. Postfreezing evaluation of cervical nodes in patients treated for oral cancers can be complicated by persistent lymphadenopathy. Cryosurgery of irradiated bone or overlying tissue can result in osteoradionecrosis. Although the possibility of these complications should not be a major deterrent when it is felt that cryosurgery is the preferred method for treating a malignancy, the complications deserve careful consideration in the management of benign lesions.


Intraoral suction drain for reduction of postoperative edema. A simple intraoral suction drain has been described. It is inexpensive, easy to fabricate in the operating room, and is convenient to use. When the drain is taped to the face, the patient has complete mobility and minimal inconvenience.


Mucormycosis of the craniofacial structures. Reports in the literature of patients surviving mucormycosis involving the craniofacial structures are exceedingly rare. The necessity for early diagnosis by recognition of any of the six key signs and symptoms is emphasized. The futility of standard diagnostic tools, other than biopsy, is noted. An underlying debilitating condition such as diabetic ketoacidosis can predispose the patient to an acute infection by this usually nonpathogenic organism. The requirement for prompt treatment of the debilitating condition together with treatment to eradicate the fungus is stressed.


Evidence for successful acceptance of irradiated free gingival allografts in dogs. Free graft samples were excised via split thickness dissection from two mongrel dogs, washed in lactated Ringer's solution, immersed into tubes containing glycerol and distilled water, and frozen to -55 degrees C. Subsequently the grafts were exposed to 2.5 x 10-6 rads of 60-Co gamma-radiation. The irradiated allogeneic grafts were later reconstituted and surgically transferred to four recipient subjects. Three autogenous nonirradiated grafts were also placed as controls. The animals were killed so as to furnish healing data at 0, 3, 7, 10, and 40 days postoperatively. Fourteen allografts were evaluated. They were judged to be nonantigenic, immunologically incompetent and nonviable. However, retention of an essentially unaltered connective tissue corium may have been instrumental in supporting subsequent epithelial regeneration from adjacent host tissue, while being passively incorporated into a very dynamic receptor zone. The graft thus served as a scaffolding for connective tissue deposition and attachment. It appears that the experimental regime obviated the immunologic interference usually encountered in allografting procedures. Thus, high intensity irradiation of the graft tissue may have rendered the tissue to be immunologically tolerable. Further studies are required to ascertain the duration of the host's immunologic unresponsiveness to the alien tissue, as well as ultimate structural and biologic fate of the transplanted tissues. Experiments are now in progress which have been designed to test the extent of immunologic sensitization induced by the grafted tissue.


Total coverage of multiple and adjacent denuded root surfaces with a free gingival autograft. A case report. A case report is presented dealing with the utilization of a free gingival autograft for the correction of gingival recession, inadequate attached gingiva, and shallow vestibular depth associated with six lower anterior teeth. A technique is described which the author believes is responsible for the successful "take" of the graft to the six vascular root surfaces.


A contiguous mucosal graft.

A contiguous mucosal graft. The contiguous mucosal graft is designed primarily for use in vestibular deepening but may serve as an adjunctive technique in the management of other mucogingival defects. A large amount of donor material can be obtained by this procedure which is relatively simple to perform and generally unattended by surgical complications of hermorrhage and excessive pain. Its benefits are esthetic as well as functional since the replaced tissue reproduces the original both in appearance and histological details.


Standardization of the epidemiologic assessment of periodontal diseases. Surveys in the South Pacific. Attempts of introducing uniform techniques for the collection of statistical data on the prevalence of periodontal diseases have been made by FDI and WHO in order to arrive at valid, reproducible, and internationally comparable results. The WHO Manual of the International Classification of Diseases. Application to Dentistry offers a five digit classification of all oral diseases for statistical purposes. In contrast to morbidity statistics, epidemiological surveys must be based on adequate samples, representative for the entire population or distinct strata thereof. FDI is actually preparing guidelines for the conduct of clinical trials in periodontal diseases, comparable to those on caries incidence, indicating the proper use of indices. For the epidemiological assessment of periodontal diseases, the WHO Basic Methods (1962, 1971) have recommended the use of simple ratios of persons affected with signs of the disease. Data collected in four extensive dental surveys in Polynesian and Melanesian populations in the South Pacific served as an example to show the variety of valid information provided by these basic methods. The main results showed an early appearance of pocket formation at ages 10 to 14, preceded in a statistically significant way by calculus formation and gingivitis. A constant pattern in the sequence of attack of the various teeth by pocket formation was shown to be specific for these island populations; males were consistently more affected than females. The character of periodontal diseases prevalent among Polynesians and Melanesians was recognized to be a "dirt pyorrhea" accompanied by progressive subgingival calculus deposition and destructive periodontitis.


The effectiveness of sodium fluoride treatment with and without iontophoresis on the reduction of hypersensitive dentin. The effectiveness of topical sodium fluoride applied with and without iontophoresis was compared in patients complaining of tooth hypersensitivity. Reduction of sensitivity to cold and mechanical stimuli was evaluated during a period of 8 months by pain scoring in the exposed cervical dentin of homologous teeth on the two sides of the jaws. There was a significant decrease in the sensitivity of the exposed cervical dentin after treatment with sodium fluoride solution, with or without iontophoresis, during the whole experimental period. There was no striking difference between the two forms of treatment with respect to the reduction of sensitivity to mechanical and cold stimuli.


A comparative study of the occlusal plane in dentulous and edentulous subjects. A study was conducted in dentulous and edentulous subjects to determine the location of occlusal plane as related to the maxillomandibular space. The results from both the dentulous and edentulous groups indicate a close angular affinity between the occlusal and maxillary planes. In the dentulous group, significant associations were found between the angulation of the occlusal plane to the maxillary plane and the height and length of the maxillomandibular space. The occulsal plane to the maxillary plane and the height and length of the maxillomandibular space. The occlusal plane in the long-and-low type of maxillomandibular space tends to be more parallel to the maxillary plane, while the occlusal plane in the short-and-high types of maxillomandibular space tends to be more steeply angulated to the maxillary plane. The occlusal plane deviates away from a mean angulation to the maxillary plane when the height and length of the maxillomandibular space tend to be toward the opposite extremes of the normal range.


The significance of the fovea palantini in complete denture prosthodontics. Clinical, radiographic, and histologic studies of the fovea palatini indicate that they were positioned 1.31 mm. (mean of 100 subjects) in front of the vibrating line. Radiographically and histologically, the foveae were located in soft tissue covering the hard palate in all specimens. Histologically, complex nerve endings were found just anterior to the foveae and spreading to the soft palate. The findings were related to clinical aspects of complete dentures.


Computerized analysis and duplication of mandibular motion. A new digital system has been devised to analyze and duplicate jaw motion. The arrangement of the electronic system offers a range of versatility which includes graphic as well as numerical data analysis. The duplicator linkage is identical to the sensor linkage which, together with an accurate model transfer system, results in an encouraging level of accuracy in jaw-motion duplication. The data collected from normal subjects should offer some new knowledge in the normal motions of the mandible as well as establish a reference for comparison with abnormal masticatory function.


Teachers as models in programs for school dental health; an evaluation of "The Toothkeeper". An evaluation of the effectiveness of the Toothkeeper program was performed in Houston to determine if participation in the program by elementary school children would result in their having cleaner teeth and better gingival health than seen in similar children not in the program. Assessments for plaque and gingivitis were made at the beginning, at the completion of the formal 16-week program, and again after a second 16-week period. In this particular setting, the Toothkeeper was found to be ineffective. Possible reasons for the ineffectiveness of the program are discussed and several suggestions for modifying the program are offered.


A comparison of the effectiveness of the "Toothkeeper" and a traditional dental health education program. A study was made of the effectiveness of two dental health education programs in an elementary school in Flint, Michigan. Following stratification by grades, random assignments of students were made by classrooms to either the Toothkeeper group or a "Traditional" group. No control groups were employed. Separate in-service training workshops were attended by the classroom teachers according to the education program to which they had been randomly assigned. An intensive 16-week program was conducted by the classroom teachers following the guidelines of the two programs. Dental examinations which included an assessment of plaque and gingivitis scores were conducted on all participants at baseline, at the end of 16 weeks, and at the conclusion of the school year, some seven months after the initiation of the program. Only minimal reductions in plaque scores were observed with either program and little comparative difference was found in the two programs at the end of the evaluation period. The Toothkeeper group experienced a somewhat greater reduction in plaque scores than the "Traditional" group during the intensive 16-week phase of the study, but these scores worsened from this time to the end of the school year. Gingivitis scores demonstrated more improvement than the reductions in plaque scores would indicate and may be related to the confounding factor of large numbers of children receiving dental treatment, especially prophylaxes during the course of this study. Differences in reductions in gingivitis between the two programs were not meaningful clinically.


Nonhematopoietic neoplasms in cats.

Nonhematopoietic neoplasms in cats. In a study of 3,145 feline necropsies conducted for 11 years by the pathology department of The Animal Medical Center, 289 tumors of nonhematopoietic origin were found in 264 cats. Malignant and epithelial tumors were more common than benign or mesenchymal tumors in all ages and breeds, and in both sexes. They were also more common in female cats than in males, even after mammary neoplasms were excluded. Analysis of groups of tumors according to their tissue of origin indicated some sex and breed dispositions not observed before. Pulmonary carcinomas and osteosarcomas were more frequent in domestic short haired cats than in other breeds, whereas intestinal carcinomas occurred more often in Siamese cats. Female predominated in pulmonary carcinomas, hemangiosarcomas, osteosarcomas, and squamous cell carcinomas, but males outnumbered the females in intestinal carcinomas.


Induction of Leukemias and digestive tract tumors in Donryu rats by 1-propyl-1-nitrosourea. Three groups of female Donryu rats were continuously given 600, 300, or 150 ppm solution of 1-propyl-1-nitrosourea in their drinking water. Leukemias developed in 62 of 109 (57%) rats surviving for more than 17 weeks and tumors developed in the digestive tracts of 31 (28%) animals. Of the leukemias, the differentiated myelocytic type was the most frequent, followed by myeloblastic leukemia and erythroleukemia. Tumors in the digestive tract, predominantly in the glandular stomach and duodenum, were both epithelial and nonepithelial. The other induced tumors were mainly in the mammary glands, ear ducts, and thymus, though the incidence was less than 15%.


Recovery of bladder function after spinal cord transection. All dogs having undergone spinal cord transection in our study exhibited a postoperative phase of spinal shock, with complete urinary retention and areflexic detrusor. This shock phase lasted between 2 and 6 weeks. Sequential pressure studies of paraplegic dogs substantiated the clinical supposition that urinary retention during spinal shock phase is caused by an unresponsive detrusor. The sphincteric mechanism could be the implicated as an etiologic agent. Return of detrusor reflex activity was observed in all animals.


Liquid breathing trials and animal studies with a demand-regulated liquid breathing system. Experimental results of in vivo animal tests conducted on a demand-regulated liquid breathing system are presented. When a liquid replaces gas as the medium in which oxygen and carbon dioxide are transported, several problems not typical in gas respiration occur. The increased mass and viscosity of a liquid as compared with a gas necessitate some means of mechanical assistance. The lower diffusion rates of gases in liquids as compared with gas rates places several constraints on the design of a mechanically assisted liquid breathing system. The liquid breathing system reported in this study has been designed to be demand-regulated, i.e., the animal has control over cycling the pumps which mechanically assist the circulation of an oxygenated liquid to and from the lungs. This system consists of a gas-operated diaphragm pump, demand controller, liquid regenerator with heater and gas scrubber, and ancillary equipment. A demand controller is described which obtains a control signal from an esophageal balloon catheter in the animal and governs operation of the pneumatically driven diaphragm pump.


Sex control in silkworms.

Sex control in silkworms. The production of hybrid silkworms yielding a very high proportion of male larvae is of great importance to the silk industry, because of the very much higher yield of silk from males. Strains giving as many as 98% male offspring have now been developed from mutants with translocations of the X chromosome.


[Acute leukemia.  Case material and therapeutic results]. In the five years period 1969-1973, 22 cases of acute lymphoblastic (ALL) and 75 of acute myeloid leukaemia (AML) were observed in adults. In ALL, complete remission was obtained in 61% of cases. The median duration of remission worked out to be 3 months in the group of patients who died and more than 6 months in the patients still alive. The mean survival time was 7,8 and more than 10,6 months respectively. The various regimens of treatment used in the  phase of induction appeared to be equally effective, whilst cyclic chemotherapy was found to be preferable in maintaining remission. As far as AML is concerned, complete remission was achieved in 25% of the patients with stem cells leukaemia, 50% in myeloblastic leukaemia and 33% in mielyomoocytic leulaemia. The median duration of remission was 3,5 and 9 months respectively. No case of promyelocytic leukaemia and erythroleukaemia achieved complete remission. The mean survival time was 3,4 months in stem cells leukaemia, 6 months in myeloblastic leukaemia, 6,6 months in myelomonocytic leukaemia, 0,4 months in promyelocytic leukaemia and 2,5 months in erythroleukaemia. In stem cells leukaemia, the highest frequency of remission was found in patients aged 13 to 20 years, whilst in myeloblastic and myelomonocytic leukaemia the most favourable results were obtained in patients aged 50 to 70 and 20 to 50 respectively. The longest mediam duration of remission and the best survival time was obtained in myelomonocytic leukaemia. The best rate of remission was achieved in the patients whose initial leukocyte count ranged from 10.000 to 50.000/mm-3. No patient with an initial WBC count above 50.000/mm-3 entered complete remission. The frequency of complete remission worked out to be much higher in the patients treated with cyclic chemotherapy according to the Hammersmith protocol, except in the case of stem cells leukaemia.


Immediate sterility after vasectomy.

Immediate sterility after vasectomy. A series of 32 males who discontinued all forms of contraception following bilateral vasectomy and irrigation of each vas with 2.5 ml of 1/1000 solution of euflavine, have been followed for one year. During this period in which coitus continued with the same frequency as before vasectomy, no pregnancy has resulted. Semen specimens examined shortly after vasectomy in all subjects showed "moderate" to "many" sperms present in one third of males, and "few" in the remaining two thirds: In all the sperms were non motile.


Non-accidental injury to preschool children in New Zealand. Serious attention must be given to the physical maltreatment of pre-school children in New Zealand if realistic solutions to presently neglected problems of maltreatment are to be devised. A concept of maltreatment is operationally defined, some available New Zelaand data discussed, and a strategy for improved prevention and treatment outlined.


A clinical trial of clonidine (Catapres) in private practice. Fifty moderately severe hypertensive patients seen in private consulting practice were treated with clonidine alone or in conjunction with diuretics and other hypertensive drugs. After six months, 38 (76 percent) were still satisfactorily controlled. Small initial dosage and cautious incrementation is needed to avoid patient resistance from side-effects, principally fatigue, dry mouth and constipation, but once satisfactory control is achieved maintenance therapy is relatively trouble free.


Porphyria cutanea tarda and the pill: case report. A patient is described who developed porphyria cutanea tarda in association with the use of a contraceptive pill. The relationship to porphyrin metabolism as at present understood, as well as the significance of abdominal pain and change in psyche, is discussed. Stopping the pill has been associated with a remission.


Accidental poisoning in children.

Accidental poisoning in children. A survey was conducted on notified cases of poisoning of children under the age of five years in the Wellington and Hutt Health Districts. Details of the fingings from a questionnaire are presented and methods of extending and modifying aspects of prevention are discussed.


Clinical experience with prazosin hydrochloride in arterial hypertension. Of 24 hypertensive patients treated with prazosin hydrochloride, a new vasodilator hypotensive drug with alpha blocking properties, 20 showed a standing blood pressure of less than 140/90 mmHg after six weeks therapy. Five patients had mild, 13 moderate and six severe hypertension. In 11 patients the drug was used alone and in 13 it was combined with thiazides, beta-blockers, clonidine or debrisoquine. Side effects were trivial. Two cases of severe renovascular hypertension responded excellently and one with malignant hypertension is showing a similar good response. The drug can be well combined with thiazides, beta-blockers and clonidine.


A comparative study of the health of elite Maori and Caucasian children in Auckland. A group of socially elite Maori and part-Maori parents kept a 10 month record (February to November 1972) of their children's health. The majority of a Caucasian control group were matched for socio-economic status by the Maori parents. The majority of both parent groups were of professional or skilled tradesman status whose income exceeded the then current New Zealand average. The results show no overall difference between the morbidity of the two racial groups studied.


The flicker-fusion threshold in schizophrenia and depression. The flicker-fusion threshold was determined in 76 patients who complained of depression and who were diagnosed as suffering from either schizophrenia or depression. It was found to be lowered in schizophrenia and lowered further in depression as compared with 28 healthy volunteers. The differences between the three groups were all highly significant with P less than 0.0005 in each case. The flicker-fusion threshold was found to be lowered by intravenous chlorpromazine and raised by intravenous amitriptyline, so it is unlikely that these differences were due to medication that the patients had been taking.


The bronchodilator effect of fenoterol (Berotec). The efficacy of the selective beta 2 sympathomimetic fenoterol (Berotec) in aerosol and tablet forms was studied in 15 subjects with reversible airways obstruction. The maximal bronchodilator effect of fenoterol by aerosol (0.4mg) was found to equal that of isoprenaline, and to be maintained at that level over the three hour period studied. When given orally, neither one tablet (2.5 mg) nor two tablets (5 mg) of fenoterol increased the FEV1 to the same extent as isoprenaline, and the larger oral dose (5 mg) produced troublesome side effects in several subjects. It is concluded that fenoterol by aerosol is an effective bronchodilator  with a duration of action of at least three hours, without significant side effects.


An attitudinal study about old people.

An attitudinal study about old people. A sentence completion instrument was administered to 28 elderly females and 44 young female social workers to investigate the differences and similarities in attitudes and beliefs about old people and being old. The statistical significance between the groups' responses was tested using the chi-square technique and individual cells by means of critical ratios. Eleven of the 20 stems were significant at the prescribed level and these are substantively discussed. It is suggested that awareness of the discrepant attitudes and beliefs is an important step towards reducing this dissonance.


The effect of dried mussel extract on an induced polyarthritis in rats. A polyarthritis was induced in a number of rats by the intradermal injection of a modified Freund's adjuvant into the right foot pad. Powered extract of New Zealand mussel fed to the rats did not have any beneficial effect on either the development or the severity of the arthritis.


[Papilledema with leukemia and similar processes]. In 11 cases of leukaemia or other lymphatic system disease meningeal affection occurred together with an oedema of optic papilla. In 6 patients (9 eyes) visual accuity fell down till 0.1 or worse. By irradiation of retrobulbar spaces in 4 of 5 cases a marked visual accuity improvement was obtained. In 2 other patients an infiltration of optic nerve was found only post mortem through histological examination. In those patients visual accuity was not diminished.


[In vitro study of sensitivity of leukemic cells to cytotoxic drugs (anticytogram)]. The in vitro sensitivity of leukemic cells to cytotoxic drugs was assessed in 61 cases of acute leukemia in adults, 49 of them were of the no lymphoblastic type and in the first phase of the disease. The depression of the incorporation of 14-C-thymidine and 3-H-uridine after a two hours incubation with the various cytotoxic drugs was compared with the clinical result obtained with two of them There is a significant correlation between the in vitro depression of the incorporation of 14-C-thymidine and the clinical effect of the drugs. This method, which may be utilized also in solid tumors, allows to predict with some accuracy the effect of chemotherapy, and to select between the various cytotoxic drugs. However the failure of a chemotherapy is generally related to an in vitro insensitivity of the malignant cells to almost all drugs.


Isolation of nuclear pore complexes in association with a lamina. Nuclear pore complexes have been isolated in association with a 150 A thick lamina by detergent and salt fractionation of nuclear envelopes from rat liver. The pore complexes exhibit characteristic morphology and appear to be attached in a highly specific orientation to the lamina, which extends over relatively large areas. The pore complex-lamina fraction is composed of three major and several minor polypeptides with little or no DNA, RNA, or phospholipid. It is suggested that the association of the pore complexes and the lamina reflects the structural arrangement of the nuclear periphery in vivo.


Control of the mRNA for hepatic tryptophan oxygenase during hormonal and substrate induction. Glucocorticoid hormones increase the level of hepatic tryptophan oxygenase (EC 1.13.11.11; L-tryptophan:oxygen 2,3-oxidoreductase (decyclizing) by increasing its rate of synthesis. Studies were performed to determine whether this induction is mediated by controlling the level of the mRNA for tryptophan oxygenase of by changing the translational efficiency of a fixed level of mRNA. Activity of tryptophan oxygenase mRNA was quantitated in a Krebs ascites cell-free, protein-synthesizing system, supplemented with tRNA and rabbit reticulocyte initiation factors. De novo synthesis of the protomeric unit(s) of the enzyme was a linear function of the amount of mRNA added. Time course and dose-response studies in which the enzyme level and mRNA activity in livers from rats injected with inducing doses of hydrocortisone were compared indicate that the induction of this enzyme is accompanied by a proportional increase in the level of its mRNA. This was true for mRNA isolated from total liver as well as from cytoplasmic polysomes. Induction of the enzyme by its substrate, tryptophan, however, was not accompanied by a parallel increase in mRNA activity.


Interaction of poly(A) and mRNA with eukaryotic initiator met-tRNA-f binding factor: identification of this activity on reticulocyte ribonucleic acid protein particles. Messenger ribonucleoprotein particles (mRNPs) have been isolated from rabbit reticulocyte polysomes. One of the proteins of the mRNP complex has many properties of a specific eukaryotic initiation factor, the soluble Met-tRNA-f binding protein. A purified preparation of this factor, in addition to binding Met-tRNA-f, binds poly(A) and globin mRNA. The binding of these substrates is greater than that obtained with other natural or artificial polyribonucleotides. The mRNP fraction also binds poly(A) and Met-tRNA-f. Since the factor which binds initiator tRNA also binds poly(A) and mRNA, and this activity can be found on mRNPs, there may be a relationship between initiator tRNA binding and messenger binding in early events of eukaryotic initiation.


Genetic complexity of aggregation in the cellular slime mold Polysphondylium violaceum. Complementation tests were performed between pairs of independently isolated aggregation defective mutants of P. violaceum. Analysis of the results suggests that the approximate number of genes controlling aggregation in this organism is 50.


Quaternary structure of chromatin.

Quaternary structure of chromatin. Neutron scattering experiments on chromatin solutions have been carried out at Bragg spacings several times larger than in any previous x-ray work. A new series of very low angle reflections at about 400, 200, and 140 A were observed. These reflections demonstrate the existence of a higher order structure of the 100 A unit fibril. A coiled-coil model with a major pitch of 500 A and a radius of center to fibril center of 130 A is proposed to explain the results.


Concanavalin A receptors on the surface membrane of lymphocytes from patient's with Hodgkin's disease and other malignant lymphomas. Concanavalin A (Con A) induces movement of its receptors on the cell surface membrane. This induction results in a concentration of Con A site complexes on one pole of the cell to form a cap. A marked difference was found in the mobility of Con A receptor between lymphocytes from normal persons and lymphocytes from patients with Hodgkin's disease and other malignant lymphomas. Lymphocytes isolated from tonsils of patients undergoing tonsillectomy and from axillary lymph nodes of breast cancer patients exhibited approximately 30% of cells with caps, which is identical with the cap formation ability of normal lymphocytes. In biopsy material from patients with Hodgkin's disease and other malignant lymphomas, a significant decrease in the ability of the lymphocytes to form caps was observed. This difference in the mobility of Con A sites was even more pronounced in lymphocytes isolated from the peripheral blood. In 123 patients with Hodgkin's disease and other malignant lymphomas, cap formation ranged between 3 and 12%. The ability of cells, from a normal donor or a lymphoma patient, to form caps was independent of the source from which the lymphocytes were isolated, e.g., lymph node, spleen, or blood. Lymphocytes from patients with lymphoma were also agglutinated by Con A to a higher degree than normal lymphocytes. These findings are discussed in relation to the association of the lymphocytes with these malignancies and as a possible aid in their differential diagnosis.


Structure of a soluble super-active insulin is revealed by the nature of the complex between cyanogen-bromide-activated sepharose and amines. Insulin-like material with elevated insulin specific acitivity is released from insulin-Sepharose in the presence of bovine-serum albumin. The mechanism of release and the chemical nature of this insulin-like material are revealed by the finding that amine-Sepharose is O-Sepharose-N-substituted isourea. Nucleophilic attack by amino groups releases N-1-N-2-disubstituted guanidines. Correspondingly, it is shown that the super-active insulin-like material is an N-1-N-2-disubstituted guanidine in which insulin and bovine-serum albumin are the substituents.


Integrative recombination of bacteriophage lambda DNA in vitro. An in vitro system for the production of integrative recombinant DNA of bacteriophage lambda is described. The in vitro recombination mimics the in vivo integration of viral DNA into host DNA in its requirement for int gene product, for the presence of a thermolabile component, and for the limitation of the recombination to a pair of specialized sites (attachment sites) on the DNA. The enzymes are extracted from Escherichia coli containing phage lambda gene products. The substrate is the DNA from lambda-attB-attP, a phage variant that contains two attachment sites on the same chromosome. The product is a recombinant phage chromosome that has lost the DNA between the attachment sites. The parental and recombinant DNA are distinguished following transfection to mature phage in spheroplasts. The reaction requires ATP, Mg++, spermidine, and a monovalent cation. Recombination occurs preferentially between attachment sites on the same molecule. The enzymatic activity is completely inhibited by extracts containing xis gene product.


Possible relationship of poly(A) shortening to mRNA turnover. Whereas the original size of poly(A) in HeLa cells is about 200 nucleotides, at steady state most of the poly(A) in mRNA contains less than 50 nucleotides. An endonucleolytic attack on poly(A) is suggested as the most likely method to accumulate short pieces of poly(A). Both poly(A) shortening and mRNA turnover appear to be inhibited by emetine, a drug that stops translation. It is possible that a random endonucleolytic attack leads to scission of poly(A) to a size below which the mRNA is unstable.


Development of a Mn-2+-sensitive, "soluble" adenylate cyclase in rat testis. A distinctive Mn-2+-sensitive adenylate cyclase [ATP pyrophosphate-lyase(cyclizing), EC 4.6.1.1] system insensitive to fluoride has been found in rat seminiferous tubules and epididymal sperm. The development of this distinctive adenylate cyclase in testis was studied during spermatogenesis. It was first detectable in seminiferous tubules in immature rats at about the time of the first reductive divisions and the appearance of spermatid cells. The specific activity of the enzyme increased substantially during the period of spermatogenesis when spermatids develop into mature spermatozoa, and reached maximal values in the testis of adult rats. After centrifugation of testis tissue homogenates at 105,000 X g for 60 min, the Mn-2+-sensitive adenylate cyclase activity was found in the cytosol. The enzyme remains in solution after centrifugation at 300,000 X g for 5 hr or at 180,000 X g for 24 hr and passes through a 0.22 mum Millipore filter. Electron microscopic examination showed no visible membrane fragments or vesicles in the filtered supernatant. The Mn-2+-sensitive adenylate cyclase system is also present in epidiymal sperm. However, in the sperm obtained from either the caput or the cauda of epididymis, the adenylate cyclase is membrane-associated and found in particulate fractions of sperm homogenates. It therefore appears that the Mn-2+-sensitive adenylate cyclase is initially present in the cytoplasm either unattached or loosely bound to intracellular membranes and becomes firmly attached to sperm membranes later in development. This occurs either during the process of maturation of spermatids into sperm or during the transport of the testicular sperm into the epididymis.


Hemoglobin synthesis in somatic cell hybrids: globin gene expression in hybrids between mouse erythroleukemia and human marrow cells or fibroblasts. Somatic cell hybrids were generated by fusion of mouse erythroleukemia cells either to mouse L cells (B82), human fibroblasts (W1-18 VA2), or human marrow fractions enriched in erythroblasts. The hybrid cells were examined for globin gene expression by benzidine staining to detect cytoplasmic hemoglobin, and by molecular hybridization of cellular RNA to globin complementary DNA (cDNA) to detect globin messenger RNA (MRNA). The fibroblast (human or mouse) times erythroleukemia cell hybrids grown in monolayer retained most of the chromosomes of each parent. Neither cytoplasmic hemoglobin nor globin mRNA was detected in dimethylsulfoxide-treated fibroblast times erythroleukemia hybrid cells, indicating extinction of hemoglobin synthesis prior to the formation of cytoplasmic mRNA. The human marrow times mouse erythroleukemia hybrid cells grown in suspension culture contained only a few human chromosomes and exhibited low levels of hemoglobin synthesis which were amplified by 2% dimethylsulfoxide. Mouse (but not human) globin mRNA was demonstrated in these hybrid cells. The results suggest that somatic cell hybrids may be useful in searching for genetic factors which regulate activity of the globin genes.


Assembly of chick brain tubulin onto flagellar microtubules from Chlamydomonas and sea urchin sperm. Flagellar microtubules from Chlamydomonas and sea urchin sperm were used as in vitro assembly sites for chick brain tubulin. Brain microtubules assembled onto the A-tubules, central tubules, and, to a limited extent, onto the distal ends of the axonemes at low tubulin concentrations and onto distal and proximal ends at high tubulin concentrations; however, the rate of assembly onto the distal end was always greater. The rate of neurotubule assembly onto axonemes was shown to be dependent upon tubulin concentration and a forward rate constant for assembly was determined.


Experimental alcohol-induced hepatic necrosis: suppression by propylthiouracil. We have previously reported that a hypermetabolic state, resembling that produced by thryoid hormones, exists in the livers of animals treated chronically with ethanol. We propose that this alteration produces a relative hypoxia in the centrilobular zone of the liver which, if severe enough, leads to cellular death and to the production of hepatitis. Rats consuming ethanol for 30 days, given with a nutritionally adequate diet, and exposed to reduced oxygen tensions for only 6 hr, developed histological and biochemical evidence of hepatocellular necrosis and inflammatory lesions confined to the centrilobular zone. The severity was proportional to the degree of hypoxia. Pair-fed (nonalcohol) controls showed no such lesions. Treatment of the animals with propylthiouracil for 3-10 days abolished the hypermetabolic state of the liver in ethanol-consuming animals, and drastically reduced the histological and biochemical effects of hypoxia in them. These findings may have implications for pathogenesis and treatment of alcoholic hepatitis in man.


Regulation of hepatic regeneration in rats by synergistic action of insulin and glucagon. Rats were subjected to resection of the gastrointestinal tract, pancreas, and spleen, and maintained by c-ntinuous intravenous infusion. Such animals, receiving only electrolytes and glucose, and deprived of a portal blood supply, responded to 68% hepatectomy with a significant rise in hepatic DNA synthesis, which was, however, greatly delayed and diminished compared to normal controls. The activity was restored to normal by infusion of insulin and glucagon (supplemented with glucose and amino acids), but not by either hormone alone; it was not decreased by delaying the start of hormone treatment for 6-7 hr after partial hepatectomy. Infusion of insulin and glucagon into a small series of rats with intact livers did not appreciably elevate DNA synthesis. In normal rats partial hepatectomy is followed by an abrupt fall in portal vein insulin concentration. These findings are all consistent with the suggestion that agents other than insulin and glucagon may serve to initiate hepatic regeneration, but that these two hormones acting synergistically are major regulators of the rate and perhaps also the extent of the regenerative process.


Changes in microtubule phosphorylation during cell cycle of HeLa cells. The phosphorylation in vitro and in vivo of tubulin isolated from HeLa cells has been examined during the cell cylce. The results obtained indicate that: (a) the protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) activity present in the microtubules, and measured in vitro with exogenous casein as substrate, is maximal in M cells, whereas that present in the cytosol is nearly constant during the S, G-2, and M stages, and decreases during G-1; (b) the patterns through the cell cycle of the maximal number of tubulin sites phosphorylated in vitro and of the microtubular protein kinase activity are similar; (c) the degree of tubulin phosphorylation in vivo is 2- to 3-fold higher in the microtubules isolated from the S and M stages of the cell cycle, than those from G-1 and G-2. This variable phosphate content of tubulin through the cell cycle suggests that such covalent modification might be important to enable tubulin to carry over some of its functions during the cell cycle.


Kinetics of oxygen and carbon monoxide binding to synthetic analogs of the myoglobin and hemoglobin active sites. Kinetics of reversible oxygenation and carbon monoxide complex formation of the simple heme compounds pyrroheme-N-[3-(1-imidazolyl)propyl]amide and pyrroheme-3-(3-pyridyl)propyl ester have been measured in different solvent environments. The oxygen on and off rates and equilibria of these compounds can be made to closely match those of myoglobin, of hemoglobin alpha chains, or of the various steps for hemoglobin by varying solvent environment or the basicity of the proximal base. These results suggest that the protein could alter oxygen on rates by varying the basicity of the proximal base and the off rates by changing the polarity of the distal environment.


Nucleotide sequence of the rightward operator of phage lambda. The sequence of 72 base pairs of the rightward operator (O-R) of bacteriophage lambda is presented as determined with simple and rapid methods for direct DNA sequencing. The sequence of an operator mutant is also described. The methods are of general use in sequencing DNA fragments with unique 5' ends up to 50 base pairs in length. Previous experiments have shown that this operator contains multiple sites recognized by the lambda phage repressor. We believe we have identified three of these sites.


Release of discrete subunits after nuclease and trypsin digestion of chromatin. Digestion of chromatin with DNase (nucleate 3'-oligonucleotidohydrolase, EC 3.1.4.7) releases 11-12S nucleoprotein particles. After extensive nuclease digestion, the DNA in these particles consists of a collection of eight discrete DNA fragments. When these nuclease-particles are treated with trypsin (EC 3.4.21.4), only 20 to 30 amino-acid residues are cleaved from histone N-terminals, the histone C-terminal segments being resistant. The resulting 5S nucleoprotein particles have now been shown on acrylamide gels to consist of a series of eight discrete DNA-containing bands. Four of these bands contain C-terminal cleavage fragments from four histones (III, IV, IIb2, and IIb1) tightly bound to them; a fifth contains fragments from only histones III and IV. The remaining three bands contain only DNA. Since these protein-free DNA bands were resistant to nuclease prior to trypsin treatment, they were presumably associated with histone N-terminal segments in the native structure. Trypsin, therefore, appears to split nuclease-particles, releasing two subfractions of DNA--one associated with protein, the other not. The data is compatible with a model in which the majority of DNA in the eukaryotic nucleus is folded into hairpin loops of double-stranded helix, each created by the concerted cross-linking action of 6 to 10 histones which interact to form a trypsin-resistant complex composed, for the most part, of all four major histones. These loops may further fold upon themselves to form the "nu" bodies that have been visualized by electron microscopy.


Crystallization of nerve growth factor from mouse submaxillary glands. Crystals of the nerve growth factor protein were grown by vapor diffusion from ethanol solution. The crystals are hexagonal, belonging to space group P622 (or its enantiomorph) with a equals 56.1 A, c equals 181.4 A, and V equals 494,400 A. The unit cell contains six molecules of dimeric protein and thus has one monomer per asymmetric unit. The diffraction pattern extends to at least 2.7 A, indicating that this crystal form is suitable for structural analysis to near-atomic resolution.


Repression and autogenous stimulation in vitro by bacteriophage lambda repressor. Purified lambda repressor protein is shown to reduce the lambda DNA-directed synthesis of proteins in vitro as determined both by net amino-acid incorporation and by analysis of specific lambda-coded proteins resolved by sodium dodecyl sulfate/polyacrylamide slab gel electrophoresis. By means of different lambda DNA templates carrying deletion and point mutations in the operators o-L or o-R, it has been possible to demonstrate repression of the synthesis of two classes of lambda proteins. The synthesis of one, class c, appears to be controlled from the operator o-L and is more efficiently repressed at low concentrations of the repressor than that of the other class of repressible lambda proteins, class d, which is controlled from the operator o-R. Several other proteins synthesized in vitro are not repressible. Some of these are coded by the J-att region. In addition, the repressor appears to have another activity, that of stimulating the synthesis of a protein identified as the repressor itself. Lambda repressor appears to stimulate its own synthesis by acting at prm, a site defined by the cis-acting mutation prm 116.


D-amphetamine disaggregates brain polysomes via a dopaminergic mechanism. Brain polysomes are disaggregated in rats given moderate to large doses of d-amphetamine sulfate; this response is rapid in onset, lasts for at least 4-6 hr, and varies with the age of the animal. Pretreatment with a dopamine receptor blocking agent, haloperidol or pimozide, blocks the amphetamine-induced disaggregation.


RNA synthesis in isolated brian nuclei after administration of d-lysergic acid diethylamide (LSD) in vivo. RNA synthesis in isolated brain nuclei was analyzed 2.5 hr after the intravenous administration of d-lysergic acid diethylamide (LSD) to young rabbits. The drug stimulated transcription by 54% in brain stem nuclei and by 13% in cerebral hemisphere nuclei expressed over saline controls. Both nucleoplasmic and nucleolar RNA synthesis were increased. The main activity in the isolated nuclei assay was due to nucleoplasmic RNA polymerase, since alpha-amanitin reduced synthesis by over 70% in either drug or control treatments.


Preparation of large monodomain phospholipid bilayer smectic liquid crystals. A technique for the preparation of large monodomain phospholipid bilayer arrays is described. Evidence for the monodomain nature of the samples, obtained from optical birefringence, light scattering, and x-ray diffraction experiments, is presented.


Identification of a ribosomal protein essential for peptidyl transferase activity. Extraction with 2 M lithium chloride removes a group of proteins (LiC1 SP) from 50S ribosomal subunits. Both the LiC1 SP and the resulting cores, which contain the remaining proteins as well as 5S and 23S RNA, lack peptidyl transferase activity, as measured by the "fragment reaction". Activity can be restored to the LiC1 cores by reconstitution with LiC1 SP under conditions of high temperature and high ionic strength. The LiC1 SP proteins were fractionated by carboxymethyl-cellulose and Sephadex G-100, and the individual fractions were tested by this reconstitution system. Of the 18 ribosomal proteins found in the LiC1 SP, only L16 is essential for reconstitution of peptidyl transferase activity.


Intermediates in the biosynthesis of double-stranded ribonucleic acids of bacteriophage phi 6. Pseudomonas phaseolicola infected with bacteriophage phi 6 synthesized all three viral double-stranded RNA segments, three single-stranded RNAs, and three replicative intermediate-like RNAs in the presence of rifampin. The single-stranded RNA intermediates sedimented and electrophoresed along with melted viral double-stranded RNA, annealed with melted viral double-stranded RNA, and were transient in nature. The relative amounts of the single-stranded RNA intermediates varied during the infection cycle and were altered in the presence of chloramphenicol. The replicative intermediate-like RNAs sedimented faster than double-stranded RNA, failed to enter 2.5% polyacrylamide gels, eluted with double-stranded RNA from a CF-11 cellulose column, were precipitated with single-stranded RNA in 2 M LiC1, and yielded three genome-size pieces of double-stranded RNA upon digestion with RNase. These results are consistent with the hypothesis that complementary strands of the phi 6 double-stranded RNAs are synthesized asynchronously during the infection cycle.


A new approach to empirical intermolecular and conformational potential energy functions. II. Applications to crystal packing, rotational barriers, and conformational analysis. An empirical potential energy function based on the interactions of electrons and nuclei (EPEN) has been tested on molecules other than those used for its parameterization. The results indicate that this energy function is able to predict reliably the lowest energy conformations, the potential energy differences between conformations, rotational barrier heights, and dipole moments for a series of alkanes, amines, alcohols, and carbohydrates. Crystal packing studies on n-hexane, n-octane, methylamine, methanol, and alpha-d-glucose, using this same potential, indicate that it is also reliable for calculating intermolecular interaction energies and low-energy orientations.


Sequence of 71 nucleotides at the 3'-end of tobacco mosaic virus RNA. The sequence of the first 71 nucleotides from the 3'-OH end of tobacco mosaic virus RNA has been determined. After total T1 ribonuclease digestion of the viral RNA, the oligonucleotide C-C-C-A-OH, which originates from the 3'-OH terminus of the RNA, may be readily detected by electrophoresis at pH 2.5 or pH 3.0; it is the only oligonucleotide that migrates toward the cathode at these pHs. This property has been used to screen the purified products of partial T1 ribonuclease digestion of tobacco mosaic virus RNA for the fragment originating from the 3'-end of the native molecule. The sequence of nucleotides in the 3'-terminal fragment, identified in this manner, was determined by radiochemical methods. The fragment contained 71 nucleotides; no abnormal bases could be detected. Although it has been reported that the 3'-end of tobacco mosaic virus RNA is a substrate for aminoacylation by the histidyl-tRNA synthetase of yeast or Escherichia coli, we were unable to fold the sequence into the cloverleaf structure characteristic of tRNAs.


Cell cycle studies of mononucleate and cytochalasin-B--nduced binucleate fibroblasts. The progress of mononucleate and cytochalasin-B-induced binucleate cells through the G1 period of the growth cycle has been studied. DNA synthesis was initiated in synchrony in both of the nuclei of cells rendered binucleate by a brief pulse of cytochalasin B. Furthermore, populations of these cells traversed the G1 period significantly faster than their mononucleate counterparts. That this effect was due to the presence of two nuclei in a common cytoplasm and not to the increased size of binucleate cells was suggested by studies of cells with altered nucleocytoplasmic ratios. No correlation was observed between protein content per cell and the rate of progress through G1. Evidence for the existence of nuclear-nuclear cooperation that results in a shortening of the G1 period is discussed.


A mitochondrial carnitine acylcarnitine translocase system. Acetylation of added (-)carnitine by heart mitochondira coupled to the oxidation of pyruvate in the presence of malonate was inhibited, apparently competitively, by long chain acyl(+)carnitines although the activity of carnitine acetyltransferase (EC 2.3.1.7) itself was not affected. Mitochondria have been found to possess a translocase system that allows the transport of carnitine and acylcarnitines by exchange diffusion, and interaction with this transport appears to be the cause of long chain acyl(+)carnitine inhibition. These c-nclusions are based on the following observations: (a) exposure of intact, but not of denatured or disrupted, mitochondria to [14-C]carnitine efflux was saturable at low lwvels of carnitine or acylcarnitines, showed temperature dependence, and was more rapid with acyl(-)carnitines than with acyl(+)carnitines--such stereospecificity was not noticeable with free carnitine; (c) long chain acyl-(+)carnitines inhibited the carnitine-carnitine exchange and higher concentrations of carnitine decreased this inhibition; (d) direct estimations showed the presence of endogenous (-)carnitine in mitochondria that effluxed by freezing and thawing of mitochondria; (e) the amount of total endogenous (-)carnitine present was not affected by prior exposure of mitochondria to (-)carnitine or acetyl(-)carnitine. These results indicate that the carnitine-dependent translocation of acyl groups across mitochondrial inner membrane involves the participation of a carnitine acylcarnitine translocase system.


Paired moving charge model of energy coupling. III. Intrinsic ionophores in energy coupling systems. The experimental basis for the postulated role of intrinsic ionophores in mitochondrial ion transport and energy coupling is summarized. Intrinsic ionophores appear to be linked to, or contained within, specific ionophoroproteins localized in the inner membrane, and the isolation of these ionophores requires their release from the ionophoroproteins. At least ten different species of ionophores have been isolated from the mitochondrion, five of which have been wholly or in part chemically identified. Intrinsic ionophores have been implicated in the activation of inorganic phosphate in ATP synthesis and hydrolysis, and in the contol of the coupling modes. The presence of ionophores in soluble proteins such as troponin and in ATP-energized kinases has been demonstrated.


Definitive evidence that the murine C-type virus inducing locus Akv-1 is viral genetic material. DNA of the AKR mouse contains a set of murine leukemia virus sequences that are not present in DNA of the NIH Swiss mouse. NIH mice partially congenic for the AKR murine-leukemia-virus-inducing locus Akv-1 contain this set of sequences, and, in a three-point cross segregating for Akv-1 on an NIH background, the sequences segregated with Akv-1. It is concluded that the Akv-1 locus contains viral sequences.


Purification and characterization of the retina-specific cell-aggregating factor. The tissue-specific, cell-aggregating component of embryonic neural retina cells was purified from the retina cell-aggregating factor and characterized as a glycoprotein. Its molecular weight in solution is in the range of 50,000, and it contains 10-15% carbohydrate. The amino-acid and carbohydrate compositions have been determined. The glycoprotein is produced by embryonic neural retina cells in primary monolayered cultures and is released into the medium. Its tissue-specific, cell-aggregating effect requires integrity of the polypeptide portion, but not of the carbohydrate portion. We suggest that the isolated molecule is a specific determinant of the embryonic retina cell-surface and that it is involved in mediating self-recognition and selective adhesiveness of these cells.


Conformation of high-molecular-weight poly(L-valine) in solid state. Poly(L-valine) in various degrees of polymerization was prepared from the N-carboxyanhydride of L-valine. The high-molecular-weight polymer was fibrous and capable of forming an oriented film when cast from trifluoroacetic acid solution. The comformations were examined by Raman spectroscopy. The Raman and infrared spectra of high-molecular-weight polymer were quite different from those of low-molecular-weight and tri-fluoroacetic-acid-treated high-molecular-weight polymers. The spectral data in the amide A, I, II, III, and V regions indicated that high-molecular-weight poly(L-valine) is possibly in the alpha-helical conformation, while low-molecular-weight poly(L-valine) and high--molecular-weight poly(L-valine) treated with trifluoroacetic acid are in the beta-conformation.


Inhibition of Balbiani ring RNA synthesis at the initiation level. The nucleoside analogue 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, a selective inhibitor of heterogeneous chromosomal RNA synthesis in salivary gland cells of the midge Chironomus tentans, blocks the initiation of transcription in Balbiani rings 1 and 2. The analogue seems to be without appreciable effect on the elongation of growing RNA chains and allows finished molecules to be detached from the chromosomal sites. The RNA chain growth rate, based on measurements of the time required for completion of synthesis of Balbiani ring 1 and 2 RNA molecules after addition of the inhibitor, was estimated to be around 25 nucleotides per second at 18 degrees.


Life games and statistical models.

Life games and statistical models. A set of equations is obtained, which describes the rules of a class of games (life games). These games simulate the processes of growth, death, survival, and competition. The equations are nonlinear difference equations, where the degree of nonlinearity is directly related to the number of interacting neighbors. The time evolution and the development of geometric patterns can be studied starting from these equations. Extensions and generalizations, such as the introduction of stochastic elements, can easily be accommodated in the formalism. Some significant unsolved problems are noted.


Presynaptic events in meiocytes of Lilium longiflorum and their relation to crossing-over: a preselection hypothesis. We are proposing a "Preselection Hypothesis" to account for the regulation of crossing-over in eukaryotic organisms. The hypothesis characterized meiosis in terms of three major physiological stages: (1) a presynaptic stage when pairs of homologous DNA stretches are selected so as to become trapped within the synaptinemal complex during synapsis, (2) an alignment of homologous chromosomes and stabilization of paired bivalents via the synaptinemal complex, and (3) a scission and rejoining of DNA stretches leading to the formation of chiasmata and crossovers. The hypothesis centers on the first stage and is based on evidence for the occurrence of significant cytological and biochemical changes prior to synapsis. The major feature of the hypothesis is that crossing-over occurs only in trapped DNA stretches. Thus, potential crossing-over sites, though not crossing-over itself, are determined well before chromosomes pair. Since, to a large degree, crossovers are distributed randomly along the length of each chromosome, the preselection process must result in a random assortment of trapped DNA stretches, the assortment differing from one meiocyte to another.


Central connections of receptors on rotated and exchanged cerci of crickets. The cerci of crickets, paired abdominal appendages bearing sound-sensitive filiform hairs, can be removed and grafted back so that their morphological axes acquire various relationships to those of the body. We have studied both the morphogenetic consequences of such surgery and the central connections made by the regenerating axons of the cercal sensory neurons. If a cercus is rotated and grafted back into its own socket, it back-rotates towards its original orientation in succeeding molts. If left and right cerci are exchanged, with or without rotation, back-rotation does not occur and super-numerary cerci are formed in predictable locations. There are two sub-populations of filiform hairs: those that vibrate transversely to the cercal shaft (T-hairs) in dorsal and ventral sectors, and longitudinally vibrating hairs (L-hairs) in lateral and medial sectors. Two giant interneurons are excited by T-hairs of their own side but not by L-hairs. If cerci are grafted so that they assume various orientations relative to the body, a consistent physiological result is obtained: T-hairs always appear to be the source of excitatory input to the giant interneurons, no matter where they are caused to be located by prior surgery. The phenomena of back-rotation, formation of supernumerary cerci, and formation of connections selectively by T-hairs, can be interpreted on the hypothesis of morphogenetic gradients.


Sexuality in the cellular slime mold Dictyostelium giganteum. By pairing of strains of Dictyostelium giganteum in various combinations this species was shown to be heterothallic. Four mating types were identified. Some strains could not be assigned a mating type and others showed no mating reaction. No self-compatible strains were found. Mutations were introduced in several strains and genetic crosses were performed. The results of these crosses show that mating and macrocyst formation are controlled by a single locus-multiple allele incompatibility system. The results also support the view that the myxamoebae that emerge upon germination of the macrocysts are the products of meiosis.


Assessment of some problems associated with prediction of the three-dimensional structure of a protein from its amino-acid sequence. It is shown that most present empirical prediction algorithms provide information about the conformational states of individual residues, but give little information about the three-dimensional structure of a protein. It is necessary to predict the conformational state of every residue before the resulting structure can serve as a starting conformation to compute the native structure. It is also shown that even a perfect five-state algorithm (which does not include long-range interactions from disulifide loop closing or solvation) will not lead to a globular structure resembling the native one. However, starting from the results of a perfect prediction algorithm, it appears that conformational energy minimization (with long-range interactions included) can lead to a structure having the general features of the native protein.


Genetic evidence for an additional function of phage T4 gene 32 protein: interaction with ligase. Gene 32 of bacteriophage T4 is essential for DNA replication, recombination, and repair. In an attempt to clarify the role of the corresponding gene product, we have looked for mutations that specifically inactivate one but not all of its functions and for compensating suppressor mutations in other genes. Here we describe a gene 32 ts mutant that does not produce progeny, but in contrast to an am mutant investigated by others, is capable of some primary and secondary DNA replication and of forming "joint" recombinational intermediates after infection of Escherichia coli B at the restrictive temperature. However, parental and progeny DNA strands are not ligated to covalently linked "recombinant" molecules, and single strands of vegetative DNA do not exceed unit length. Progeny production as well as capacity for covalent linkage in this gene 32 ts mutant are partially restored by additional rII mutations. Suppression by rII depends on functioning host ligase [EC 6.5.1.2; poly(deoxyribonucleotide):poly(deoxyribonucleotide) ligase (AMP-forming, NMN-forming)]. This gene 32 ts mutation (unlike some others) in turn suppresses the characteristic plaque morphology of rII mutants. We conclude that gene 32 protein, in addition to its role in DNA replication and in the formation of "joint" recombinational intermediates, interacts with T4 ligase [EC 6.5.1.1; poly(deoxyribonucleotide):poly(deoxyribonucleotide) ligase (AMP-forming)] when recombining DNA strands are covalently linked. The protein of the mutant that we describe here is mainly defective in this interaction, thus inactivating T4 ligase in recombination. Suppressing rII mutations facilitate substitution of host ligase. There is suggestive evidence that these interactions occur at the membrane.