Lipsarcoma of the cheek.

Lipsarcoma of the cheek. A case of liposarcoma of the cheek in a 39-year-old man has been presented. This tumor, which is one of the most common malignant tumors of soft tissues in the body generally, is extremely rare in the oral regions. Initial surgical excision in this case was followed closely by a second more extensive local dissection in view of the pronounced tendency of the liposarcoma to infiltrate locally beyond the apparent limits of ite pseudocapsule. Early and adequate surgical intervention is most important in the long-term control of this tumor. Accurate histopathological diagnosis provides important information relative to the prognosis and preferred treatment.


Fractures of the edentulous mandible: the Chalmer J. Lyons Academy study. Results of a study show a 20% incidence of nonunion of fractures of atrophic edentulous mandibles. Accurate bony reduction is essential in elderly paatients with thin mandibles. Closed reduction should be tried first as open reduction tends to limit vascular supply to the fracture. Maintenance of periosteal coverage seems advisable if open reduction is necessary. Bone grafting should be considered unless contraindicated because of the patient's age or physical condition. Wire mesh is preferable to bone plates for stability.


Surgical-orthodontic approach to skeletal class III malocclusion. Twenty-nine adult patients with skeletal Class III malocclusion were treated by combined surgical-orthodontic management. A thorough analysis enabled us to point out the exact location and degree of the deformity and was of great help in determining the appropriate types of treatment. Corrections were made in 12 patients by the mandibular body ostectomy in the premolar region; the curved oblique osteotomy, in which the ascending ramus was cut obliquely on a curved line from the anterior border of the ramus to the angle, was used for the treatment of the remaining 17 patients. The resulting profile and occlusal improvements were satisfactory, Preoperative orthodontic treatment such as leveling of the dental arches, expansion of the upper dental arch to accommodate the maxilla to the mandible, correction of the upper and lower incisal inclinations, extraction of the premolars to decrease horizontal discrepancy or alignment of malpositioned teeth, and postoperative adjustment were effective in providing definite changes in profile and a stable occlusion-an important factor in the prevention of postoperative relapse.


Palatal patch-grafts in post areas of subperiosteal implants. Transplantation of palatal patch-grafts before insertion of subperiosteal implants can be helpful in producing a better stress-bearing area for a prosthesis. Careful use of the technique assures adequate attached mucosa around the implant posts and reduces the possibility of infection and wound dehiscence.


Subgingival plaque and loss of attachment in periodontosis as observed in autopsy material. Histologic sections from six autopsy cases which from a clinical point of view fitted into the criteria of periodontosis were examined with the aim at evaluating the role of subgingival plaque in the etiology of the loss of attachment in this condition. The following pertinent observations were made: 1. The subgingival plaque in most instances was not calcified to form calculus. 2. The thickness of the subgingival plaque varied between 20 and 200 mu (0.02-0.2 mm). 3. Where loss of attachment had taken place, the distance from the most apical part of the subgingival plaque to the most apical point of the epithelial cuff varied between 0.2 and 1.1 mm; this distance was never found to be more than 1.1 mm. This would indicate a cause and effect relationship, the plaque being the obvious cause. 4. There was very severe chronic inflammation in the soft tissue bordering upon the plaque with resulting collagenolysis. 5. The cellular infiltration and the collagenolysis may be limited to a zone of 1 to 2 mm in the immediate vicinity of the plaque. Between the inflamed area and the surface of the gingivae buccally and lingually there may be a fairly wide zone of healthy tissue which hides the symptoms of inflammation from being observed on a clinical examination. In turn this could leave the clinician with the impression that attachment has been lost and bone resorbed because of degenerative changes. The following conclusions can be made: In these six cases of "alveolar bone loss vastly out of proportion to what one would expect from the local etiologic factors in the patient at that age" there was no morphologic evidence that degenerative changes were responsible for the loss of attachment. On the contrary inflammatory changes induced by the subgingval plaque dominated the histopathologic picture.


Histopathology of periodontal disease in sheep. A histological investigation was carried out of the periodontia of young and mature sheep obtained from areas where a periodontal syndrome is endemic in sheep flocks. Observations of the incisor periodontia, which are most commonly affected by the syndrome, revealed no evidence of degenerative or pathological changes of alveolar bone, periodontal ligament or cementum compared with the periodontia of control animals. Minor inflammatory changes of the gingivae, associated with small amounts of a filamentous-type dental plaque, were noted in young animals from areas where the disease is endemic. In mature animals moderate to severe inflammatory periodontal disease with deep pocketing was evident together with dental plaque in the sheep from periodontal disease-prone areas; whereas control specimens showed minimal inflammatory response and dental plaque. It was concluded that periodontal disease in sheep can be described as a localized inflammatory disease initially of the gingivae and later of the deeper periodontal disease.


The depth of the vestibular fornix in the mandibular anterior region in health. Using a radiographic technique, the depth of the vestibular fornix in the lower anterior region was determined for 100 periodontally healthy subjects. The width of attached gingiva was measured clinically. The vestibule in the mandibular anterior region was found to be approximately uniform in depth for each individual from canine to canine, being reduced where there were frenal and muscle attachments. The depth, measured from the gingiva to mucobuccal fold, varied from 2.5 to 11.5 mm; and. measured from the crest of the lip to mucobuccal fold, varied from 10 to 29 mm. The proportion of the vestibule, measured from gingiva to mucobuccal fold, occupied by attached gingiva, varied from a mean of 34% in the canine region, to approximately 60% in the lateral incisor region, and to approximately 55% in the central incisor region. The minimum depth of the vestibule determined was 2.5 mm, and this was associated with a zone of attached gingiva 1 mm wide. Considering that all subjects in this study were periodontally and gingivally healthy, it would appear that satisfactory periodontal and gingival health may be maintained even where the vestibule is shallow.


Periodontic/orthodontic management of diphenylhydantoin gingival hyperplasia: case report. A case report of the periodontic/orthodontic management of a patient with diphenylhydantoin gingival hyperplasia is presented over a 38-month period. The interdependence between the two specialties is discussed along with the rationale for treatment, based upon empirical and available scientific knowledge.


Location of flap margin after suturing.

Location of flap margin after suturing. Facial and lingual flaps were reflected on 23 patients who required an apically positioned flap procedure. Immediately after suturing, the distance from the flap margin to the crest of the alveolar process was recorded by routine pocket probing techniques. Root coverage was about 2 mm, significantly greater than the coverage previously recommended.


Complete dentures and the associated soft tissues. Some of the conditions of the soft tissues related to complete dentures encountered during a period of 25 years at a university clinic were presented and discussed from the standpoint of the clinical prosthodontist. During this time, over 1,000 denture patients were treated each year. For some conditions, a method of management was offered with treatment by sound prosthodontic principles rather than unneccessary medication. That denture fabrication involves much more than mere mechanical procedures is an understatement. Complete dentures are foreign objects in the oral cavity that are accepted and tolerated by the tissue to a degree that is surprising. As prosthodontists, we can gain satisfaction from the realization that the incidence of oral cancer due to dentures is less than extremely low. At the same time, we must be ever mindful of the statement by Sheppard and associates. "Complete dentures are not the innocuous devices we often think they are." Every dentist must remember that one of his greatest missions is to serve as a detection agency for cancer. The information discussed indicates (1) the need for careful examination of the mouth, (2) the value of a rest period of 8 hours every day for the supporting tissues, and (3) the importance of regular recall visits for denture patients. Robinson stated that while the dental laboratory technician can be trained to aid the dentist in the fabrication of prosthetic devices, his lack of knowledge of reactions and diseases of the oral tissues limits him to an auxiliary role. Complete prosthodontics is a highly specialized health service that greatly affects the health, welfare, and well-being of the patient. It can be rendered only by the true professional who is educated in the biomedical sciences.


Variations in mandibular rest positions with and without dentures in place. As part of a seven-year study concerning variations in denture techniques, seven radiographs were made for 52 patients. Three films of the series were made with dentures in the mouth and the patient at the vertical relation of rest; three films were made with the dentures out of the mouth and the patient at the vertical relation of rest; and one film was made with the patient at the vertical relation of occlusion. Differences were computed using an average of the three films for both groups. It was determined that the vertical relation of rest is affected by the presence of dentures in the mouth. However, this difference was not predictable, since with the dentures out, 25 per cent of the patients showed an increase in vertical relation, 59.6 per cent showed a decrease, and 15.4 per cent showed very little change.


The continuing role of the prosthodontist in the treatment of patients with cleft lip and palate. The prosthodontist can fill a unique position on the cleft-palate team by aggressive participation in every phase of treatment for the developing child. Neonatal prostheses allow for normal feeding and help to direct proper tongue position. Palatal obturation is essential during all growth and tooth development. When orthodontic treatment is necessary and a pharyngeal extension prosthesis is present, obturation can be maintained with flexible denture liners. Each individual situation will allow utilization of an innovative type of prosthesis.


Radiation complications in edentulous patients. Complete dentures were fabricated for 88 patients following completion of cancericidal doses of radiation therapy to the head and neck regions. All were followed for at least 6 months after delivery. All patients received dentures resting within the radiation field. Three patients developed osteoradionecroses directly attributable to their dentures. These three had been dentulous prior to therapy and had either pre- or posttreatment extractions. Of the 58 patients who had been edentulous prior to therapy, none developed osteoradionecrosis. Five patients developed soft tissue necroses secondary to the use of dentures.


The measurement of jaw movement. Part I. A new method of recording the movements of a point on the mandible appears to be a valuable addition to the many means which are available for attempting to fathom the secrets of jaw movements. While in its present form this method does not fully describe any of the movements of the jaws, the over-all patterns recorded may be of significance.


A reliable reline-rebase technique.

A reliable reline-rebase technique. A reliable reline-rebase technique is very important to the general dentist. There are many excellent techniques, but this particular one has provided the most consistent results and patient satisfaction. No technique has any value unless a careful treatment plan is followed and technical procedures are performed with skill and concern.


An evaluation of terminal hinge position and neuromuscular position in edentulous patients. Part I. Maxillomandibular recordings. The purpose of this investigation was to obtain information about the terminal hinge position (THP) and the neuromuscular position (NMP) in the edentulous population. The difference between the two positions was evaluated anteroposteriorly and mediolaterally to determine horizontal differences and reproducibility between days. In 25 edentulous subjects, five recordings were made at the neuromuscular position with no dentist guidance and five recordings at the terminal hinge position with dentist guidance; on a second day, the recordings were repeated. The differences between positions were evaluated by statistical methods. It was concluded that: (1) there is a discrepancy between the THP and the NMP for all edentulous subjects examined, (2) the NMP is anterior and medial or lateral to the THP, and (3) the NMP is not as reproducible as the THP.


A method of transferring mandibular-movement data to computer storage. A method was briefly described which photographed engraved blocks of mandibular-movement recordings and transferred the information into computer memory. A photographic platform was designed to allow uniform photographing of the engraved blocks. The photographed information was then projected onto graph paper where it was traced. The traced information, with the centric point labeled, was transferred into computer memory via a Computek 531 tablet. An RMS (root-mean-squared) deviation test was conducted to estimate the reliability of this technique. The maximum deviation (0.363 mm.) was found for z coordinate of the left-side recording. Labeling the centric point in computer memory is very important. This allows careful and detailed study of movements in the area where clinical evaluation is of utmost importance to the dentist. As more data are collected and evaluated, questions related to occlusion, such as tooth stability, effect on periodontal health, relationship to orthodontic success, and the like, may be clarified.


Scanning electron microscope study of the junction between restorations and gingival cavosurface margins. This study demonstrates a definite interfacial void between the cervical margins of the tooth preparation and gold inlay, composite resin, and amalgam restorations. In addition, these marginal defects permit plaque formation within them. Furthermore, microleakage may be a complicating factor in this lack of fit. Restorations which may be "clinically acceptable" may not, in fact, be ideal because of the properties of the restorative materials. It would seem desirable, therefore, to encourage the development of new restorative materials that will bond to the tooth surface.


An evaluation of techniques for finishing margins of gold inlays. The following conclusions on finishing margins of gold inlays were reached: 1. Instruments should be rotated perpendicular to the margin from gold to enamel. 2. Green stones produce rough surfaces that are not easily smoothed by finer instruments. 3. Hand burnishers and rubber points are not effective in producing gross marginal closure. 4. The best instruments for finishing occlusal margins are round steel burs, finishing burs, or white finishing stones. 5. When finishing occlusal margins, it is important to use an instrument small enough to gain access to the depth of grooves and fissures. 6. Proximal preparations made with a secondary flare yield castings with better "as cast" and finished margins than those preparations made with a butt joint. 7. The best instruments for finishing proximal margins are flexible paper discs. Usually, one fine sand or fine cuttle discs are necessary. 8. There is an indication that castings made from slightly overwaxed patterns can be finished to produce better margins than those made from patterns waxed exactly to the margins.


A review of concepts of silver amalgam retention. Retention grooves and undercuts are not advantageous to an amalgam cavity preparation. These mechanical locks do not prevent fracture of the proximal portion in vivo, do not inhibit marginal fracture, are not necessary for retention, and are a factor in the split-tooth syndrome. The tensile stress needed to dislodge the restorations would be impossible to achieve in the oral environment, and therefore, additional retention is not worth the added risk of endangering the integrity of the tooth and the pulp. All factors considered, a properly prepared, conservative Class II Black's type of cavity preparation not only remains the easiest to prepare with conventional instrumentation but also is totally adequate to withstand the stresses of mastication, magnifying the desirable properties of the amalgam restoration.


Light-weight RTV silicone for maxillofacial prostheses. Weight is a problem in retention of large skin-textured maxillofacial prostheses. The purpose of this investigation was to test the feasibility of mixing foam RTV silicone rubber with conventional RTV silicone rubber to obtain a light-weight material. Various mixtures of foam and conventional silicone rubber were formulated and tested for strength, accuracy of molding, color application, color stability, and texture. A special flask to support the mold was necessary in order to overcome expansion problems associated with gas formation of the foam silicone rubber. The mold required venting to release the gas and to reduce the expansion of the prosthesis in order to maintain accuracy. Molding, accuracy, texture, and color problems were overcome. Reduction of weight proportionate to reduction of tear strength of the material formulated, however, did not allow routine use of mixtures of foam and conventional silicone. When the weight of a prosthesis is critical and excessive and thickness is sufficient to give adequate strength, the foam and conventional silicone mixture can be used.


Titanium endosteal dental implants in the mandibles of beagle dogs: a 2 year study. Forty of 44 vented endosteal blade implants were well tolerated by the mandibular tissues of beagle dogs, as demonstrated clinically, radiographically, and histologically. Infection and inflammation were not observed. The epithelium did not invade along the neck of the implants more than 2 mm. below the mandibular crest. After 3 to 6 months, except for increasing density of bone at the metal interface, no distinct pattern of reaction could be discerned histologically. Except for heavy collagenous investment in three dogs, there was no sign of the implants being treated as sterile foreign bodies. In this study, histology did not provide good criteria for evaluating the failure of vented endosteal blade implants. In four implants which failed, the most reliable signs of failure were increased mobility and/or sulcus depth around the neck of the abutments. Radiographic evaluation of implants provided the best means of determining bone resorption. Bone resorption was apparent 3 to 6 months after implantation, did not appear to be progressive, and did not indicate implant failure or impending implant failure in those animals in which it occurred. Radiolucent areas observed in 29 of the specimens contained connective tissue, marrow spaces, thin bone trabeculae, and nonpathologic tissues. Although in some of the dogs stress on implants did not cause failure, there is a need for further experimentation involving vented endosteal blades subjected to occlusal loading.


Reflectance spectra of natural and acrylic resin teeth. A method has been described for determining the reflectance spectra of teeth at various parts of the tooth surface. The shape and size of the teeth were accounted for by appropriate experimental and mathematical techniques. In all instances where a subtle difference in tooth color was discernible, this difference was also apparent on the corresponding spectra. The spectra of acrylic resin teeth showed characteristic absorption shoulders caused by pigmentation. These shoulders did not appear in the spectra of natural teeth where the reflectivity gradually increased with increasing wavelength. Differences were observed in the colors as well as the spectra of teeth from different shade guides which were marked with the same shade number by the manufacturer. The method may be applied for control of the color quality of artificial teeth as well as the selection of pigments in order to obtain an appropriate shade range and to reduce effects of metamerism.


Chronic myelocytic leukemia and the myeloproliferative diseases during the child-bearing years. Chronic myelocytic leukemia and the myeloproliferative diseases may present as asymptomatic elevations of peripheral blood counts or with relatively nonspecific symptoms. Full diagnostic evaluation is necessary to eliminate the many other causes of blood count elevation. Coincidence of a myeloproliferative disease and pregnancy is unusual. The pregnancy has no adverse effect on the course of the mother's hematologic disease. However, the myeloproliferative diseases, especially if uncontrolled, result in increased fetal prematurity and mortality. Treatment of the pregnant patient should be conservative, and cytotoxic therapy should be avoided until at least after the first trimester whenever possible. Busulfan has been the drug most widely used during pregnancy, and it appears not to cause fetal malformations when used alone.


Microcirculation of the renal papilla of rats under control conditions and after temporary ischemia. Blood flow velocities were measured and, with the help of vessel diameters, volume flow rates were calculated in the ascending and descending vasa recta of the renal papilla of young rats using microkymography. Measurements were done under control conditions, and one or three days after temporary ischemia of the kidney (one hr of renal artery occlusion). To test whether the osmolality of the final urine which surrounds the papilla influences the papillary microcirculation, the papillary surface was rinsed with 300 or 1500 mOsm solutions. However, the rinse fluid osmolality had no effect on blood flow. Flow velocity in descending vasa recta(hypertonic rinse fluid) averaged 0.60 +/- 0.04 SEM mm/sec under control conditions, 0.68 +/- 0.08 mm/sec one day after temporary ischemia, and 0.73 +/- 0.04 mm/sec three days after temporary ischemia. The corresponding blood flow rates are 9.3 +/- 1.0, 8.3 +/- 1.2, and 10.5 +/- 1.5 nl/min; these values are not significantly different from each other. Flow rate in the ascending vasa recta was 6.4 +/- 0.6 nl/min under control conditions and 9.3 +/- 1.2 nl/min one day postischemia. The significance increase in ascending vasa recta blood flow after ischemia was probably due to an increase in the permeability of the papillary epithelium. An exact quantitative comparison between blood inflow and outflow from the papilla is not possible at present, because it is not yet clear to what extent the number of ascending vasa recta outnumber the descending vasa recta.


Quinsy tonsillectomy.

Quinsy tonsillectomy. The usual treatment for peritonsillar abscess in the United States is incision, drainage and antibiotic therapy followed by tonsillectomy several weeks later. Why this treatment began is not clear but it probably originated from fear of complications which might arise from operating during the acute stage. This therapy requires two hospitalizations and tonsillectomy after previous abscess can be difficult. Tonsillitis or peritonsillar abscess can recur any time after the initial abscess is treated. A series of 50 cases of peri-tonsillar abscesses treated by immediate tonsillectomy is presented and evaluated. The results show this operation has a low morbidity and no significantly greater complication rate than elective tonsellectomy.


Immunotherapy with chemotherapy in the maintenance of remission in acute myeloblastic leukaemia. Thirteen patients with acute myeloblastic leukaemia or one of its variants in remission have been given maintenance treatment with a combination of chemotherapy and immunotherapy. Chemotherapy was given for one week in four, and immunotherapy was given during the intervening three weeks. The immunotherapy consisted of BCG vaccine given by Heaf gun, and snap-frozen pooled allogeneic irradiated leukaemic cells. The median duration of survival was 147 weeks, and the median duration of the first complete remission was 76 weeks. It is difficult to compare these results with other figures reported, but they add to the evidence which suggests that immunotherapy is of value in the maintenance treatment of patients with this disease. Further controlled trials are necessary.


L-asparaginase reinduction and maintenance therapy in previously treated acute lymphocytic leukemia. Four patients with acute lymphocytic leukemia previously treated with conventional chemotherapy received intramuscular L-asparaginase in combination with other chemotherapy for reinduction and maintenance therapy. These patients received the L-asparaginase for 8, 14, 27, and 34+ months without demonstrating any significant adverse effects. Only 1 of the 4 was clearly resistant to the other chemo-therapy, and 3 of 4 had recurrence of their disease while receiving L-asparaginase. L-asparaginase can be added to reinduction and maintenance regimens of patients resistant to other chemotherapy and is well tolerated for long periods when given intramuscularly weekly with other immunosuppressant agents.


Cytogenetic studies in acute lymphocytic leukemia: special emphasis in long-term survival. Cytogenetic studies were performed in 331 patients with ALL diagnosed at the National Institutes of Health between January 1961 and January 1976. Four patients had constitutionally abnormal genotypes, three had Down's syndrome, and one had a D/G translocation. Aneuploidy was observed in the pretreatment bone marrow in 49/115 (42.6%) of this series exhibited several general characteristics: aneuploid cells usually coexist with normal stem cells, hyperdiploidy is predominant and wide ranging aneuploidy clusters around a major cell line. The most common chromosomal group involved in aneuploidy is the G group (p=0.001) and the next most common is the B group (p=0.01). Aneuploidy disappeared after successful achievement of remission, and new clones developed in 12 patients during relapse. Two of the four patients originally thought to have a Ph1 chromosome, on trypsin Giemsa handing were proved to have a 21q- chromosome. A higher incidence of aneuploidy was noted in patients under one year or more than 20 years of age and was also higher in patients with low or elevated WBCs at diagnosis. The appearance of aneuploid cells in the bone marrow at the onset or later in the disease is of no prognostic significance but persistence of these lines and the development of total aneuploidy signals a poor prognosis. Eradication of aneuploid cells is therefore essential for the achievement of a long remission and progress to a permanent cure.


The toxicity of 90Sr, 226Ra and 239Pu.

The toxicity of 90Sr, 226Ra and 239Pu. Data now available on the risks of radiation-induced fatal cancer and hereditary disease and radionuclide metabolism suggest that limits on the rates of intake of 90Sr, 226Ra and 239Pu at work, presently recommended by the International Commission on Radiological Protection, might be in need of considerable revision one with another and with the limit for uniform exposure of the whole body.


[Diagnostic difficulties in a case of leukemia with radicular symptoms]. The author describes a 20-year-old patient with leukaemia and with meningoradicular symptoms. The first neurological symptoms developed 2 years after disclosure of haematological changes. Despite treatment with steroids, intrathecal Methotrexate and radiotherapy the patient died 3 years after the diagnosis of leukaemia had been established. Myeloblastic leukaemia was confirmed on autopsy. The importance of early intrathecal Methotrexate treatment is stressed.


[Hydrocortisone in the treatment of painful syndromes of the cervical spine]. The authors used hydrocortisone POLFA injecting it paravertebrally in painful syndromes of the cervical spine. The clinical material comprised 50 patients divided into groups A and B of 25 patients each. In both groups typical anti-inflammatory and analgesic agents and muscle relaxants were given and physiotherapy was applied. In group B hydrocortisone was given additionally in injections. Better therapeutic effects were obtained using hydrocortisone which alleviated acute pains and shortened considerably the duration of treatment.


Utilisation of multiple biochemical tests in a large general hospital. This report gives an account of the patterns of requesting of multiple biochemical tests in a large general hospital and the frequency of abnormal test results in different hospital departments. There are appreciable differences between some areas in the frequency of requests for multiple testing and in the proportions of abnormal results. If it is assumed that clinicians should be aware of abnormal values and their progress, facilities for multiple testing are desirable and economically justifiable.


Hepatitis B surface antigen in notified cases of viral hepatitis. Eighty-five patients notified to the local medical officer of health as infectious or serum hepatitis during the period 1 September 1974-1 September 1975 were investigated by questionnaire. Serum from 73 cases was tested for the presence of HBsAg. Sixteen cases were notified as serum hepatitis but only 13 were shown to have HBsAg in their serum. Sixty-eight cases were notified as infectious hepatitis and 21 HBsAg positive cases were found amongst the 57 sera tested. Two-thirds of the HBsAg positive cases were not suspected clinically. The epidemiology of hepatitis in Christchurch is discussed and suggestion is made that all notified cases of hepatitis should have blood tested for HBsAg.


The role of vehicle safety glass in eye injuries. Despite the introduction of compulsory seat belt legislation, the incidence of eye injuries, and their severity, is greater in Auckland, New Zealand, than in London, Canada. A comparison has been made between Auckland (83 cases) and London (50 cases) in a survey from 1 July 1970, to 31 December 1974. Consideration is given to the fact that New Zealand vehicles are equipped with heat-toughened (tempered) glass, whereas in Canada, vehicles are fitted with laminated windscreens.


Creep in amalgam class V restorations.

Creep in amalgam class V restorations. The purpose of the investigation was to examine the creep rate in an amalgam Class V restoration. The stresses in a central bucco-lingual plane of a loaded bicuspid with a Class V restoration were computed with aid of the finite element method. When the stresses were known, the creep rate was calculated. The results showed that the creep rate of a load of 150 N varied between 0.6% and 3.5% per 104 s for amalgams with large differences between their viscoelastic behaviors. A gap between the restoration and the cavity margin will thus occur if a tooth is often heavily loaded.


Long-term effects of activator (Andresen appliance) treatment. A clinical, biometric, cephalometric roentgenographic and functional analysis. The purpose of this investigation was to analyse the long-term effects of activator treatment on the dental arches and arch relationships, the dento-facial skeleton and the function of the masticatory system. A follow-up study was performed on 112 patients treated 10-20 years previously with activators as the sole orthodontic appliance. In connection with activator treatment extractions of permanent teeth were performed on 66 patients while 46 patients were treated without tooth extractions. The investigation consisted of four separate portions (Parts I-IV).


Immediate vestibuloplasty with fenestrated and intact full-thickness mucosal grafts. Intact and fenestrated full-thickness palatal mucosal grafts were placed following immediate vestibuloplasty in ten dogs of mixed breed. Macrscopic and microscopic findings indicated that the fenestrated grafts were as effective as the intact grafts in long-term maintenance of bestibular depth.


Cardiovascular responses to intraosseous injections of prilocaine containing vasoconstrictors. A study of the cardiovascular responses to prilocaine hydrochloride (Citanest) given by intraosseous injection showed that there were no effects related to the absorption of this anesthetic. The presence of epinephrine in concentrations of 1:2000,000 was detected by its rapid absorption and stimulation of the heart rate. The injection of octapressin with prilocaine hydrochloride was usually accompanied by no heart rate or blood pressure changes. However, the heart rate decreased slightly in a few subjects, and this slower heart rate returned to preinjection values within 5 minutes.


Collagen gel in osseous defects. A preliminary study. In a preliminary study, the effects of a biodegradable collagen gel on the healing of osseous defects were examined. Histologic and biochemical observations made on the seventh day after placement revealed that the collagen gel is well tolerated by the recipient and might be an effective stimulator of the formation of reparative bone. However, between the seventh and fourteenth days after placement, the deposition of reparative osseous tissues at the site of implant was significantly retarded. The possible implication of these findings is discussed.


Allergic response to stainless steel wire. A review of the literature indicates that an allergic response to stainless steel is rare, although nickel is a common allergen and is encountered continually in daily life. An allergic reaction could occur at a most inopportune time. Rational approaches in management of an allergic response to stainless steel appear to be either: (1) wire removal and symptomatic therapy, (2) application of fixation with other substances, or (3) administration of steroids with necessary stainless steel immobilization left in place. The report suggests the need for research to determine the chromium content or chromium-nickel ratio that would eliminate allergic manifestations to the nickel component in wrought or cast base metal dental appliances.


The histologic evaluation of teeth transplanted between weakly disparate, genetically defimed mice. Teeth transplanted between inbred lines of mice that differ by strong histocompatibility barriers are promptly rejected. However, when only one weak antigen difference exists between donor and recipient, teeth are known tp survive indefinitely. The purpose of this study was to determine if the histocompatibility barrier could be increased to two weak antigens without inducing a rejection episode. Allografted teeth was examined from 30 to 210 days after transplantation and, contrary to expectations, the teeth were rejected at about 60 days. Thus, all but the weakest of histocompatibility barriers are sufficient to cause the rejection of tooth allotransplants in mice.


Scrotal tongue and geographic tongue: polygenic and associated traits. The familial nature of scrotal and geographic tongue was investigated in parents and siblings of 156 probands having these conditions. The prevalence in parents and siblings was significantly higher than that in the control populations. The prevalence in sibilings from families in which at least one parent was also affected was significantly higher than that in siblings from families in which neither parent was affected. The prevalence of scrotal tongue alone in siblins was similar irrespective of the condition in the proband. The prevalence of geographic tongue alone was highest in siblins of probands having only geographic tongue. A polygenic mode of inheritance with some genes common to both conditions is suggested.


Oral acantholytic itching disease responding to dapsone. Dermatitis herpetiformis, pemphigus, or a new disease? A patient had a blistering and severely itching disease confined solely to the oral cavity. The histopathologic findings had the features of both pemphigus and dermatitis herpetiformis. There were no gastrointestinal symptoms, no IgA could be found in uninvolved skin, and no intercellular or basement membrane antibodies were present in the serum or epidermis. The disease responded favorable to dapsone (diaminodiphenylsulfone), which could be discontinued after 2 1/2 years. The literature is briefly reviewed, and there is a discussion of whether the patient was suffering from pemphigus or dermatitis herpetiformis. The conclusion is drawn that the diagnosis cannot be established with certainty and that we are perhaps dealing with a new disease. It is stressed that in such aberrant cases a therapeutic trial with dapsone should be made.


Electron microscopic changes in rat parotid and submandibular glands subsequent total body irradiation with fast neutrons. Female Sprague-Dawley rats wre irradiated with fast neutrons to study the radiobiologic effect on the parotid and submandibular salivary glands. Cytologic alternations were seen in the parotid tissues as early as 3 hours after exposure and peaked in both parotid and submandibular glands by the fourth postradiation day. The injury was manifest as damaged and sequestered intracytoplasmic organelles appearing as pleomorphic inclusions. The two types of glandular tissue showed similar morphologic alterations. No injury to blood vessels or other radiosensitive cells could be found.


Report of a kindred with bone lesions and subcutaneous abscesses of unknown etiology. This case report concerns a 12-year-old boy who had a 9-year history of mandibular lesions of unknown origin. The mandible showed changes resembling chronic osteomyelitis. The tibia and temporal bone also exhibited radiolucencies. Many subcutaneous abscesses were present. The boy died at the age of 14 years as a result of rupture of the aorta. In his family, there were seven members who had bone lesions and eleven who suffered from skin abscesses.


A histopathologic, histobacteriologic, and radiographic study of periapical endodontic surgical specimens. Data available on 230 periapical endodontic surgical specimens were studied. It was found that bacteria occurred in the periapical tissue very infrequently. In addition, there was no correlation between the presence of acute inflammatory cells and the presence or absence of pain. Granulomas with epithelium occurred in 61 out of 230 cases, while 14 of these were cysts. Of the 110 cases with radiographic follow-up data, 67 were classified as successful, 40 were uncertain, and 3 were unsuccessful according to a modification of Strindberg's criteria, whereas 107 would have been successes according to the criteria of Bender and Seltzer and their associates. No valid biologic or clinical basis for endodontic therapy as suggested by Bhaskar was found in this material.


Endodontics and the irradiated patient.

Endodontics and the irradiated patient. With increasingly larger numbers of irradiated patients in our population, it seems likely that all denists will eventually be called upon to manage the difficult problems that these patients present. Of otmost concern should be the patient's home care program and the avoidance of osteroradionecrosis. Endodontics and periodontics are the primary areas for preventing or eliminating the infection that threatens osteoradionecrosis. Endodontic treatment must be accomplished with the utmost care and maximum regard for the fragility of the periapical tissues. Pulpally involved teeth should never be left open in an irradiated patient, and extreme care must be taken with the between-visits seal. If one is called upon for preradiation evaluation, routine removal of all molar as well as other compromised teeth should be considered. Attention should be directed to the literature for further advances in the management of irradiated patients.


Dynamic tomography.

Dynamic tomography. Dynamic tomography is a radiographic procedure that allows details in a thin layer within the patient to be examined. This layer can be moved at will throughout the patient. Thus, details lying in an infinite number of layers can be scrutinized one layer at a time. Eight underexposed radiographs are made under rigid controls. Each film receives one fourth of a normal exposure. The "in focus" layer of details is about 0.5 mm. thick. Various future applications of the technique are discussed.


A radiographic study of nutrient canals. The purpose of this investigation was to determine the incidence of nutrient canals in a randomly selected population and to correlate the presence of nutrient canals with a variety of factors related to the life of the individual. One hundred sixty patients, 25 years of age or older, having at least six teeth in each arch and requiring a complete-mouth radiographic survey were used. Nutrient canals were found associated with race, high blood pressure, advanced periodontal conditions, multidirectional trabeculae, and small trabecular spaces.


Cystic fibrosis: enzymatic detection of a ciliostatic factor. The ciliostatic cystic fibrosis (CF) factor has been investigated in order to develop an enzymatic assay for its detection. In saliva, this factor is associated with alpha-amylase. Removal or addition of the factor by dialysis does not affect the alpha-amylase catalytic activity of CF or control (normal) saliva. Crude preparations of the dialyzable factor from CF saliva are ciliostatic. Alpha-Amylase-catalyzed starch hydrolysis from both CF and control saliva was found to be insensitive to hydroxyalkylamine inhibitors so this method could not be used to detect differences in CF and control amylase. Since another carbohydrase, mammalian debranching enzyme, is much more sensitive to inhibition, the effect of the isolated crude factor on this enzyme was determined. The mean values for percentage of inhibition of debranching enzyme activity by fractions obtained from saliva of CF patients, obligate heterozygotes, and control subjects are: 32% (27 samples), 13% (21 samples), and 6% (11 samples), respectively. Fifteen of the CF values exceed the maximum 13% inhibition observed for controls. Indeed, five samples almost completely inhibited debranching enzyme. This inhibitory action provides the basis of an enzymatic assay for the detection of the ciliostatic CF factor.


[Some measurements of doses to patients in dental radiography]. Some measurements of doses to patients by conventional dental radiography and orthopantomography are presented. Doses to the red bone marrow are calculated. The bonemarrow doses by two different exposures, Maxilla incisor and Molar bite-wing, were calculated to 0.4 and 1.0 mrad respectively. The average dose to red bone marrow from a full-mouth examination (10 exposures) was 0.7 mrad/exposure, An orthopantomographic examination involved 2 mrad to the bone marrow. The greatest doses by an orthopantomographic examination were found around the lateral rotational axis, namely 700 mrad. The dose distributions by the two different cone lengths did not differ as much as expected, mainly due to scattered radiation.


[The falls not far from the tree. Occurrence of dental caries among 3 year-old children in relation to their parents' background]. 113 children 3 years of age, living in a rural community in Norway, were examined. 59% of the children were born in 1970 and examined in 1973, the remaining were born in 1971 and examined in 1974. The caries experience was described by caries scores based on 1 point for each decayed tooth and 2 points for each root. 51% of the children were caries-free, 26% had 1-4 caries scores, and 24% had 5 or more caries scores. The dental health of the children born in 1971 was better than that of children born in 1970, a finding which hardly could be ascribed to encreasing use of fluorides only. There was a significant association between the childrens' caries experience and their age at the examination, and particularly with their social background. The treatment pattern and the oral health habits of their parents, which in turn were dependent on social background, had conceivably an early and distinct influence on the dental health of their children.


Nature of O2 and CO binding to metalloporphyrins and heme proteins. The O2 vibration of dioxygen adducts of Fe and Co model complexes of alpha,alpha,alpha,alpha-tetrapivalamidophenylporphyrin ("picket fence" porphyrin, TpivPP) with 1-methylimidazole and 1-tritylimidazole as axial bases are reported, obtained with difference techniques between 16O2, 18O2, 169-18O, and NO with a Fourier transform infrared spectrometer. Assignments of upsilono2 are (O2)Fe(TpivPP) 1-methylimidazole, 1159 cm-1 in Nujol; (O2)Fe(TpivPP) 1-tritylimidazole, 1163 in benzene; (O2)Co(TpivPP) 1-methylimidazole, 1150 in Nujol; (O2)Co(TpivPP) 1-tritylimidazole, 1153 in benzene. Comparisons with other known Fe, Co, Cr, and Ti dioxygen complexes are made, and it is concluded that the bent dioxygen ligand is best viewed as bound superoxide, O2-. The CO affinities of various hemoproteins and model systems are discussed. A correlation between the CO stretching frequency and its binding constant is described. The drastically lowered affinity of hemoproteins for CO compared with unencumbered models is attributed to steric hindrance in the distal binding site, which allows discrimination between the already bent FeIII-O2- and the normally linear FeII-CO systems. If the affinity of hemoproteins in living systems for CO relative to O2 were not decreased, then massive poisoning would result from endogenous CO.


Carbon monoxide binding to pentacoordinate mercaptide-heme complexes: kinetic study on models for cytochrome P-450. Mercaptide anions form exclusively penta-coordinate heme complexes [RS-heme] in polar and nonpolar solution over a wide range of mercaptide concentration. These complexes have a Soret peak at 408 nm and a formation constant of about 2.5 X 10(4) M(-1), and combine with CO to give a CO-cytochrome P-450 type spectrum. Kinetics of CO binding to mercaptide-heme complexes [RS-heme] have been studied by the flash photolysis method. Characteristic constants for this reaction suggest close similarities between [CH3-(CH2)3-S-heme] and cytochrome P-450. The reaction of alkoxide anion with heme has also been examined but no evidence was found for the existence of the [RO-heme-CO[ species.


Ethidium bromide-(dC-dG-dC-dG)2 complex in solution: intercalation and sequence specificity of drug binding at the tetranucleotide duplex level. The binding of ethidium bromide (EtdBr) to the dC-dG-dC-dG self-complementary duplex has been monitored at the resolvable drug and nucleic acid protons and backbone phosphates at high nucleotide/drug (N/D) ratios by nuclear magnetic resonance (NMR) spectroscopy in aqueous solution. We observe averaged resonances (25 degrees-95 degrees) for the nucleic acid and drug nonexchangeable protons in the presence of excess tetranucleotide (N/D = 24), indicative of rapid exchange relative to the chemical shifts in the free and complexed states. Complex formation results in upfield shifts for the base protons at the terminal and internal base pairs and an increase in the transition midpoint for the duplex-to-strand conversion. We observe upfield chemical shift changes of 1.2 ppm at the Watson-Crick guanine N-1 proton(s) on complex formation (N/D = 24), with slow exchange between (dC-dG-dC-dG)2 and EtdBr-(dC-dG-dC-dG)2 relative to this chemical shift difference at-5 degrees. The EtdBr phenanthridine ring protons shift upfield by about 0.9 ppm (H-2, H-4, H-7, H-9) and greater than 0.5 ppm (H-1, H-10) on complex formation, with the chemical shifts versus temperature plots (25 degrees-95 degrees) monitoring the dissociation of the EtdBr-(dC-dG-dC-dG)2 structure. These upfield shifts at the exchangeable and nonexchangeable base protons and phenanthridine ring (but not side chain) protons demonstrate intercalation of the phenanthridine ring of EtdBr into the dC-dG-dC-dG duplex in solution. The intercalation model may be supported by the observation of downfield shifts (up to 1ppm) at the internucleotide phosphate(s) of the tetranucleotide duplex on addition of EtdBr at low temperatures. We observe stronger binding of EtdBr to the self-complementary dC-dG-dC-dG (2 dC-dG intercalation sites) and dC-dC-dG-dG (1 dC-dG site) duplexes compared to the dG-dG-dC-dC (no dC-dG sites) as monitored by UV absorbance changes at 480 nm. These studies extend to the tetranucleotide duplex level earlier observations that EtdBr exhibits a selectivity for formation of complexes to dinucleoside monophosphates with a pyrimidine (3'-5') purine sequence in the crystal and in solution. The experimental proton NMR upfield shifts at the phenanthridine protons on formation of the EtdBr-(dC-dG-dC-dG)2 complex compare favorably with calculated values (atomic diamagnetic anisotropy and ring current contributions) based on the overlap geometry for EtdBr intercalated into the pyrimidine (3'-5') purine dinucleoside monophosphate duplex in the crystal.


A structural model of radiation effects in living cells. The chance mechanism of cell damage and of repair in the course of irradiation involves two details familiar to biologists that thus far seem to have been overlooked in mathematical treatment. One of these details is that, generally, the passage of a single "primary" radiation particle generates a "cluster" of secondaries which can produce "hits" that damage the living cell. With high linear energy transfer, each cluster contains very many secondary particles. With low linear energy transfer, the number of secondaries per cluster is generally small. The second overlooked detail of the chance mechanism is concerned with what may be called the time scales of radiation damage and of the subsequent repair. The generation of a cluster of secondary particles and the possible hits occur so rapidly that, for all practical purposes, they may be considered as occurring instantly. On the other hand, the subsequent changes in the damaged cells appear to require measurable amounts of time. The constructed stochastic model embodies these details, the clustering of secondary particles and the time scale difference. The results explain certain details of observed phenomena.


Dynamic properties of isolated acetylcholine receptor proteins: release of calcium ions caused by acetylcholine binding. Interaction of Ca and acetylcholine (AcCh) ions with purified acetylcholine receptor (AcChR) from Torpedo californica and Electrophorus electricus has been investigated in view of these ions' role proposed in bioelectricity. Spectrophotometric Ca titration using murexide as an indicator and an ultrafiltration method with 45Ca show that AcChR proteins have a high binding capacity for Ca ions. Per macromolecule of 260,000 daltons, up to 60 Ca ions can be bound with at least three Ca dissociation constants. A linear inhibition of AcCh binding to AcChR by Ca was observed in the 0.1-1 mM Ca range, indicating competition of AcCh and Ca for AcChR. The addition of AcCh to a Ca-AcChR solution at 1.2 mM Ca causes release of four to six bound Ca ions from AcChR when a maximum of two AcCh ions are bound per 260,000 dalton macromolecule. The subsequent addition of alpha-bungarotoxin causes reuptake of up to six Ca ions by AcChR. These results suggest that the neural activator AcCh and the inhibitor alpha-bungarotoxin induce opposing shifts between different conformational states of isolated AcChR.


Primary structure of the gamma-carboxyglutamic acid-containing protein from bovine bone. The amino-acid sequence of the gamma-carboxyglutamic acid-containing protein of bovine bone is presented. The sequence of 43 of the 49 residues was determined automatically on the intact protein and on a tryptic peptide. The remainder was determined by conventional procedures on tryptic and chymotrytic peptides. Residue 9 in the sequence has been identified as 4-hydroxyproline. The protein contains three gamma-carboxyglutamic acid residues, which are located at positions 17, 21, and 24. The role of these unusual amino acids in the binding interaction between the protein and hydroxyapatite crystals is discussed.


Metabolism of benzo[a]pyrene: conversion of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene to highly mutagenic 7,8-diol-9,10-epoxides. Metabolites of (+/-)-trans 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene formed by a rat liver microsomes and by a highly purified monoxygenase system were analyzed by high-pressure liquid chromatography. Four stereoisomeric tetraols of 7,8,9,10-tetrahydrobenzo[a]pyrene, known solvolysis products of the two highly mutagenic stereoisomers of the 9,10-epoxide of the 7,8-dihydrodiol, were identified as products. The ratio of the two highly unstable diol epoxides formed (7 beta,8alpha-dihydroxy-9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, diol epoxide 1; 7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, diol epoxide 2) ranged from about 1.7 to 0.4. The diol epoxides are sufficiently reactive to alkylate phosphate buffer (pH 7.4) at 37 degrees. Microsomes, particularly those from control animals, formed a substantial amount of an additional metabolite that appears to be phenolic. In analogy to benzo[a]pyrene, the metabolism of the 7,8-dihydrodiol shows similar induction after pretreatment of rats with phenobarbital or 3-methylcholanthrene. Neither diol epoxide appears to be a substrate for epoxide hydrase based on the ratis of tetraols formed in the presence or absence of epoxide hydrase. In view of the known carcinogenicity of benzo[a]pyrene 7,8-oxide and 7,8-dihydrodiol and of the marked mutagenicity of the stereoisomeric diol epoxides, both of these diol epoxides qualify for consideration as "ultimate carcinogen(s)" of benzo[a]pyrene.


A possible explanation for the nuclease limit digestion pattern of chromatin. The general pattern of DNA fragments in the limit digest of nuclease-treated chromatin could arise from a single, unique nuclease-susceptible site per nucleosome. If DNA binds to the histone core of the nucleosome along a circularly re-entrant path, the location of the DNA entrance and exit can occur at any of a number of distinct sites. This very specific type of heterogeneity together with the natural 10-fold periodicity of DNA B can account for the observed digestion pattern. Such a general picture of the nucleosome structure could also easily explain how nucleosomes might move along the DNA. This type of structure should be easy to distinguish experimentally form more conventional explanations of the origin of the limit digest pattern of chromatin.


Methods for identification of recombinants of phage lambda. Two methods are described which allow the screening of a large number of phage plaques for a specific DNA sequence carried by the phage or a specific antigen produced within the phage plaque. These methods were set up with lambda and lambdalac phages. Phage plaques were transferred onto nitrocellulose filters by desiccation in 0.1 M NaOH, and the lac sequence was detected by hybridization to radioactive lac mRNA. Beta-Galactosidase was detected by reaction with anti-beta-galactosidase immune serum included in the soft agar of the titration plates; the precipitate thus formed was revealed by means of enzyme-coupled antibodies and in situ coloration. These methods are potentially useful for the identification of lambda transducers, including those which are generated by in vitro recombination with eukaryotic DNA.


Amino-acid sequence of equine renal metallothionein-1B. The amino-acid sequence of a metallothionein is reported. Metallothionein is a widely distributed, extremely cysteine-rich, low-molecular-weight protein containing large amounts of cadmium and/or zinc. Metallothionein-1B is one of the two prinicipal variants occurring in equine kidney cortex. The single-chain protein contains 61 amino acids and has the composition Cys20 Ser8Lys7Arg1Ala7Gly5Val3Asp2Asn1-Glu1Gln2Pro2Thr1Met1(Cd + Zn)7. Its amino-terminal residue is N-acetylmethionine. The sequence shows distinct clustering of the twenty cysteinyl residues into seven groups separated by stretches of at least three other residues. Within these groups the cysteines occur seven times in alternating Cys-X-Cys sequences and three times each in Cys-Cys and Cys-X-X-Cys sequences, where X is an amino acid other than cysteine. Another unique feature is the close association of serine and the basic amino acids with cysteine, as manifested by the occurrence of seven Ser-Cys, four Cys-Lys, one Cys-Arg, and three Lys-Cys sequences. These findings are in agreement with the previous suggestion that metallothionein has structurally defined metal-binding sites, most of which contain three cysteinyl residues as the principal metal-binding ligands. The charge difference between the metal-free and the metal-containing protein is consistent with the formation of negatively charged trimercaptide complexes with cadmium and/or zinc ions. The possible additional involvement of serine and the basic amino acids in metal binding is discussed.


Amplification of moderately repetitive DNA sequences during chick cartilage differentiation. A 5-bromo-2'-[3H]deoxyuridine (BrdUrd) probe was isolated to analyze DNAs obtained from various chick tissues and cell types. [3H]BrdUrd-substituted DNA, prepared from limb bud cultures, was sheared and freed from palindromic DNA. Nonradioactive DNA was prepared from embryonic liver, undifferentiated limb bud mesenchyme, sternal cartilage, differentiated limb bud cultures, and BrdUrd-blocked cultures, and was sheared. These DNAs were used in 100-fold excess to drive the reassociation of the [3H]-BrdUrd-DNA probe. Purified mature cartilage DNAs of embryonic sternae or differentiated limb bud cultures drove the reassociation of the probe approximately two times faster than did DNA from liver, undifferentiated limb bud, or BrdUrd-blocked cells. These data indicate that cartilage DNA contains a greater number of sequences complementary to the BrdUrd probe than do DNAs of noncartilage or undifferentiated precartilage cells. Calculations determined an average substitution of 10% of thymidine residues by BrdUrd in purified probe, whereas CsCl density gradients of unsheared probe revealed radioactive peaks of greater than 20% substitution. The BrdUrd appears to be clustered in the genome.


Stimulation of hepatic glycogen synthesis by amino acids. Hepatocytes isolated from livers of fasted rats form little glycogen from glucose or lactate at concentrations below 20 mM. Glycogen is formed in substantial quantities at a glucose concentration of 60 mM. In the presence of 10 mM glucose, 20-30% as much glycogen as glucose is formed from fructose, sorbitol, or dihydroxyacetone. The addition of either glutamine, alanine, or asparagine stimulates the formation of glycogen from lactate 10- to 40-fold. The formation of glucose and glycogen is then about equal, and glycogen deposition in hepatocytes is similar to rates attained in vivo after fasted rats are refed. The amino acids stimulate 1.5- to 2-fold glycogen synthesis from fructose, and 2- to 4-fold synthesis from dihyDROXYACETONE. Ammonium chloride is about one-half as effective as amino acids in stimulating glycogen synthesis when glucose with lactate are substrates. It increased glycogen synthesis 25-50% from fructose but inhibited synthesis from dihydroxyacetone plus glucose.


Nature of conformational changes in poly[d(A-T)-d(A-T)] in the premelting region. The conformation of the synthetic DNA, poly-[d(A-T)-d(A-T)], has been investigated both in the solid state and in dilute aqueous solutions at different temperatures below its melting point. The change of the circular dichroism (CD) spectra of poly[d(A-T)-d(A-T)] solutions with decreasing temperatures from just below the melting point to 0 degrees involves a specific decrease of the intensity of the 262 nm CD band. This conformational change has been assigned to a gradual and partial transition from the B to C form, on the basis of the following results: (i) By the use of infrared dichroism measurements on oriented films we have defined humidity and salt conditions under which B and C forms of poly[d(A-T)-d(A-T](Li+) are stable. In addition, we find that ammonium salts induce the C form of poly[d(A-T)-d(A-T)] even at high relative humidity. (ii) CD studies of the films of the lithium salt of poly[d(A-T)-d(A-T)] under the same conditions have given CD spectra corresponding to the B and C forms of this polynucleotide. In addition, the CD spectrum of the ammonium salt of poly[d(A-T)-d(A-T)] in solution approaches that of the C form in films. (iii) The conformational change of poly[d(A-T)-d(A-T)] as a function of temperature can be entirely explained on the basis of changes in the double-stranded base-paired structure. Our data rule out hydrogen bond breaking and unstacking or "breathing" as an explanation of the premelting changes. Curves of the continuous variation of CD(epsilon at 262 nm) as a function of temperature (from 0 degrees to the melting zone) show similar slopes in the presence of different agents stabilizing the double-stranded structure, such as Mg++, or at different salt concentration (KCl), indicating that the nature of the process is independent of ionic strength. Some specific effects were observed in the influence of certain neutral salts; ammonium induces the C form whereas magnesium favors the B form. CD data give direct evidence that a DNA like poly[d(A-T)-d(A-T)] need not change conformation upon transition from a dilute aqueous solution to a highly hydrated (film/gel) solid state. The change of conformation begins only at a defined partial dehydration.


Identification of nonhistone chromatin proteins in chromatin subunits. Rat liver chromatin was digested by micrococcal nuclease. More than 80% of the enzyme-digested chromatin could be recovered after centrifugation. Treatment with sodium deoxycholate and Triton X-100 at concentrations of 0.5% in the final chromatin suspension gave a higher recovery. Chromatin subunits were fractionated on a 5-30% linear sucrose density gradient. Approximately 35% of the chromatin subunits could be recovered from the gradient. Chromatin subunits and their DNA fragments were identified by gel electrophoresis and ultracentrifugation. The presence of nonhistone chromatin proteins (NHCP) in chromatin subunits was demonstrated by the following criteria: (i) Quantitative analysis showed that the mass ratio of histone to NHCP, in the presence or absence of detergents, was 1:0,25 or 1:0.1, respectively. (ii) After the removal of acid-soluble protein from the subunits, it was found that most of the phenol-soluble NHCP were similar to total chromatin NHCP. However, four major fractions of these phenol-soluble NHCP were found to be enriched in the subunits as identified by two-dimensional polyacrylamide gel electrophoresis. (iii) Experiments using an exchange of isotope-labeled and nonlabeled chromatin showed that NHCP were tightly bound to the chromatin subunits.


Choleragen-mediated release of trapped glucose from liposomes containing ganglioside GM1. 125I-Labeled choleragen was bound to liposomes containing galactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosylglucosylceramide (GM1), but not in large amounts to ganglioside-free liposomes nor to those containing N-acetylneuraminylgalactosylglucosylceramide (GM3), N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosylglucosylceramide (GM2), or N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosylglucosylceramide (GD1a). Choleragen released trapped glucose only from GM1-liposomes. This choleragen-induced glucose release from GM1-liposomes was relatively rapid for the first few minutes, then continued more slowly. The amount of glucose released from liposomes in 30 min was dependent on both the GM1 content and choleragen concentration. Prior incubation of GM1-liposomes with anti-GM1 antiserum prevented the choleragen-dependent release of trapped glucose. After incubation of GM1-liposomes with choleragen, addition of anticholeragen antibodies and complement led to more extensive glucose release. Under these latter conditions a much smaller glucose release was observed also from liposomes containing GM1 or N-acetylneuraminylgalactosyl-N-acetylgalactosaminyl-(N-acetylneuraminyl)-galactosylglucosylceramide in the absence of choleragen. These releases were attributed to naturally-occurring antiganglioside antibodies in the antiserum and complement. Ganglioside-free liposomes did not release glucose in response to anticholeragen and complement. It appears that choleragen in the absence of other proteins binds specifically to liposomes containing GM1 and can induce permeability changes.


Absence of low-molecular-weight alpha crystallin in nuclear region of old human lenses. Examination of old human lenses indicates that low-molecular-weight alpha crystallin is not present in the inner 30-40%, the nucleus, of the lens. The remainder of such lenses, the periphery, contains normal levels of this protein. This finding is in marked contrast to observations in young lenses, where a large quantity of this protein is found throughout the tissue.


Evidence for an intermediate with a single-strand break in the reaction catalyzed by the DNA untwisting enzyme. The DNA untwisting enzyme relaxes covalently closed circylar DNAs by the sequential breaking (nicking) and closure of one strand of the duplex. The use of highly purified enzyme from rat liver nuclei at very high protein concentrations has permitted the detection of the nicked intermediate in the reaction. The nicking of closed circular simian virus 40 DNA was measured by alkaline sucrose gradient sedimentation or by equilibrium centrifugation in CsCl gradients containing propidium diiodide. The following observations support the hypothesis that the nicked DNA represents an intermediate in the untwisting reaction. The extent of nicking does not increase with time. Nicking is observed in the range of salt concentrations where the enzyme is active (0.01-0.25 M KCl), but is not observed at 0.50 Mkdl, where enzyme activity is undetectable. The nicked DNA that is generated during the reaction carried out in low salt rapidly disappears if the KCl concentration is raised to 0.50 M. At constant enzyme concentration, the number of nicks in the reaction mixture is independent of DNA concentration in the range from 3 to 14 mug/ml. The addition of an excess of unlabeled DNA to a reaction initially containing labeled nicked DNA partially chases the label from the nicked intermediate into covalently closed circular DNA.


On the mechanism of delayed inhibition of protein synthesis in heme-defecient rabbit reticulocyte lysates. In the absence of added hemin, protein synthesis in a rabbit reticulocyte lysate declines abruptly (shuts off) after about 5 min at 30 degrees. In these studies we have examined the basis for the lag period preceding shut-off. The initiation factor that binds Met-tRNAf, previously shown to be rate-limiting in inhibited, heme-deficient lysates, is found to be used stoichiometrically in the presence of excess inhibitor. We suggest that a principal effect of the inhibitor is to impair the recycling of the Met-tRNAf-binding factor; the lag period is attributable largely to the presence of a pool of excess Met-tRNAf-binding factor, which, once used in initiation, cannot be recycled because of the action of the inhibitor.


Mapping of in vivo messenger RNAs for bacteriophage phiX-174. In vivo messenger RNA for bacteriophage phiX174 was fractionated in agarose gels into a number of discrete species ranging in size from 0.23 X 10(6) to 2.3 X 10(6) daltons. These RNA species were eluted from the gels and hybridized to specific fragments derived from phiX-174 replicative form DNA by cleavage with restriction enzymes. A map of the orientation of in vivo messenger RNAs with respect to the bacteriophage genetic map was constructed. This map indicated that initiation of messenger RNA occurred before gene B, gene C or D, and probably before gene A and that termination occurred after genes E, F, G, and H. Termination of transcription at any particular site appeared not to be entirely effective such that a number of overlapping transcripts with the same 5'-terminus was observed. Messenger RNA for gene A seemed to be relatively unstable.


Restriction assay for integrative recombination of bacteriophage lambda DNA in vitro: requirement for closed circular DNA substrate. A novel assay has been developed for in vitro genetic recombination of DNA. Substrate and product DNAs are cleaved with a restriction endonuclease and the resulting fragments are separated by electrophoresis in agarose gels. The substrate DNA has been chosen so that the recombination to be studied deletes a segment of DNA. The remaining DNA gives rise to a unique restriciton fragment, as does the DNA segment that has been removed. The method provides a convenient and physical, rather than genetic, assessment of the conversion of parental to recombinant DNA. This method has been applied to an in vitro system that carries out integrative recombination of bacteriophage lambda. We find that, different molecular forms of DNA tested, closed circular DNA is the only efficient substrate. Linear DNA and three kinds of circular DNA containing interruptions are at best very poor substrates. The implications of this surprising result are discussed. In addition, we show that the in vitro recombination system completes the breaking and rejoining steps of recombination. No stable DNA intermediates involving chiasmata or broken end structures are found.


Glycosylation of hemoglobin in vitro: affinity labeling of hemoglobin by glucose-6-phosphate. To determine the mechanism for the formation of hemoglobin A1c (Hb A1c) in vivo, we incubated human hemoglobin with glucose and metabolites of glucose. [14C]Glucose-6-phosphate (G6P) reacted readily with deoxyhemoglobin, and formed a covalent linkage. The reaction rate was considerably reduced in the presence of carbon monoxide or 2,3-diphosphoglycerate (2,3-DPG). Purified G6P hemoglobin had a lowered oxygen affinity and decreased reactivity with 2,3-DPG compared to Hb A. G6P behaved as a 2,3-DPG analog and reacted specifically at the NH2-terminal amino group of the beta chain. In contrast, the interaction of hemoglobin with glucose was much slower, and was unaffected by carbon monoxide or 2,3-DPG. Neither glucose-1-phosphate, fructose-6-phosphate, nor fructose-1,6-diphosphate formed a reaction product with hemoglobin. G6P behaves as an affinity label with the phosphate group forming electrostatic bonds at the 2,3-DPG binding site and the aldehvde group reacting with the NH2-terminal amino group of the beta chain. Thus, G6P hemoglobin may be an intermediate in the conversion of Hb A to Hb A1c.


Kinetic evidence for hapten-induced conformational transition in immunoglobin MOPC 460. The kinetics of hapten binding to the homogeneous immunoglobulin A secreted by the murine plasmacytoma MOPC 460 was investigated by the chemical relaxation method. Two distinct relaxation times were observed in the binding equilibrium with three different haptens. A detailed concentration dependence analysis of relaxation times and amplitudes was performed with the hapten epsilon-N(2,4-dinitrophenyl)-lysine (Dnp-Lys). The results support a mechanism in which two interconvertible conformational states of the protein bind the hapten with different association constants. Hapten binding shifts the equilibrium towards the better binding state. These observations form kinetic evidence for a conformational transition induced in the immunoglobulin by ligand binding to its antigen binding site, and are in line with the allosteric hypothesis for the initiation of physiological functions by antigen-antibody association.


Temperature dependence of the four ionic processes of spike electrogenesis in eel electroplaques. Spike electrogenesis of eel electroplaques involves four ionic processes which are controlled by the membrane potential. A threshold depolarization causes normally closed Na permselective channels to open (Na-activation) and normally open K channels to close (K-inactivation). The Na channels then close (Na-inactivation), and as the spike is terminated, the K channels reopen (K-reactivation). The temperature dependence of these four processes has been examined in the present work. Opening of the Na channels and closure and reopening of the K-channels are either effectively instantaneous or are relatively independent of temperature in the range of at least 5 degrees to 22 degrees. Closure of the Na-channels has a Q10 (increase in rate of reaction for each 10 degrees increase in temperature) of about 9, and activation energy (Ea) of this reaction is about 31.5 kcal/mole (132 kJ/mole).


Calorimetric studies of the in vitro polymerization of brain tubulin. The enthalpy change for chain propagation in the polymerization of bovine tubulin has been studied directly by stopped-flow microcalorimetry at 17 degrees and 25 degrees, and found to be 0 +/- 1 kcal per mol of 6S tubulin dimer at both temperatures. Substantial heat evolution with a half-time of decay of approximately 1 hr was observed w-en tubulin was injected into the calorimeter. This heat was shown to result from contamination of the tublin by small amounts of some material from the crude brain homogenate from which the tubulin was prepared, and to be totally unconnected with microtubule assembly. Model calculations of nucleated polymerization processes reveal that the van't Hoff enthalpy calculated from the temperature dependence of the critical polymerization concentration is a complicated function of the separate enthalpy changes for nucleation and chain propagation. The published values of this quantity for tubulin probably pertain primarily to the nucleation process. It is shown that our observation of a propagation enthalpy change of vanishingly small size is not necessarily inconsistent with the reported van't Hoff enthalpies.


Correlation between tumor induction and the large external transformation sensitive protein on the cell surface. The distribution on the cell surface of the large external LETS protein that is transformation sensitive of normal, transformed and tumorigenic cells was examined by immunofluorescent staining. A correlation was established between the expression of fibril-like LETS protein and the oncogenic capabilities of a series of adenovirus-transformed cell lines. In cells expressing a transformed phenotype in vitro, LETS protein is only detected in cell-cell contact areas, wheras in "untransformed" cells LETS protein is distributed over the cell surface. Transformed cells capable of inducing invasive tumors, and the cells of established tumor lines, have low or undetectable levels of LETS protein, as measured by this method. The results indicate that LETS protein has a role in cell-cell adhesion and that reduced expression of this protein at the cell surface is related to the oncogenic phenotype. This relationship has been established for experimentally induced and spontaneous tumors.


The relationship between in vitro cellular aging and in vivo human age. Differences between early and late passage cell cultures on the organelle and macromolecular levels have been attributed to cellular "aging". However, concern has been expressed over whether changes in diploid cell populations after serial passage in vitro accurately reflect human cellular aging in vivo. Studies were therefore undertaken to determine if significant differences would be observed in the in vitro lifespans of skin fibroblast cultures from old and young normal, non-hospitalized volunteers and to examine if parameters that change with in vitro "aging" are altered as a function of age in vivo. Statistically signigificant (P less than 0.05) decreases were found in the rate of fibroblast migration, onset of cell culture senescence, in vitro lifespan, cell population replication rate, and cell number at confluency of fibroblast cultures derived from the old donor group when compared to parallel cultures from young donors. No significant differences were observed in modal cell volumes and cellular macromolecular contents. The differences observed in cell cultures from old and young donors were quantitatively and qualitatively distinct from those cellular alterations observed in early and late passage WI-38 cells (in vitro "aging"). Therefore, although early and late passage cultures of human diploid cells may provide an important cell system for examining loss of replicative potential, fibroblast cultures derived from old and young human donors may be a more appropriate model system for studying human cellular aging.


Hormonal stimulation of DNA synthesis in primary cultures of adult rat hepatocytes. Adult rat hepatocytes have been previously isolated and maintained in monolayer culture, but attempts to stimulate DNA synthesis have been unsuccessful. Hormonal conditions are now described which induce DNA synthesis in cultured hepatocytes from partially hepatectomized rats. DNA synthesis was determined autoradiographically by the incorporation of [3H]thymidine into nuclei of morphologically distinct hepatocytes. Insulin (4-4000 nM) or epidermal growth factor (10 ng/ml) alone caused significant increases in the labeling index. The two hormones together acted synergistically to produce labeling indices of 35-50% on the third day of culture, compared with 2-7% in control cultures. The addition of glucagon (400 nM) further increased the labeling indes. Dexamethasone (80 ng/ml) inhibited DNA synthesis but, under certain conditions, enhanced cell attachment. Growth hormone and triiodothyronine had no significant effect on DNA synthesis. The mixture of epidermal growth factor, insulin, and glucagon also stimulated incorporation of [3H]thymidine into phenol-extracted DNA. Although DNA synthesis was stimulated, cell division occurred infrequently. These data suggest a prominent role for epidermal growth factor in promoting hepatic DNA synthesis by acting in concert with insulin and glucagon.


Isolation of retina-specific cell-aggregating factor from membranes of embryonic neural retina tissue. There is increasing evidence that developmental associations among embryonic cells are mediated by specific components of the cell surface. Earlier work has indicated that such components are extruded into the medium of primary monolayer cultures of embryonic cells, and that they represent the active constituents of the tissue-spedific cell-aggregating factors isolated fro- the supernatant medium of such cultures. We presently report that tissue-specific cell-aggregating factors can be obtained directly from embryonic tissues, and describe the isolation and partial purification of retina-spedific factor from a cell-membrane preparation derived from retina tissue of the chick embryo. Extraction of the purified membrane preparation with 1-butanol yielded an activity in the aqueous phase which resides in a protein probably a glycoprotein, with an estimated molecular weight of 50,000 in solution. This material could be obtained from retinas of embryos not older than 13 days, and only pre-13-day cells responded to its cell-aggregating activity. By these characteristics, this membrane-derived retina factor closely resembles the retina cell-aggregating glycoprotein previously purified from the supernatant medium of retina cell cultures. It is of special interest that the cell-aggregating protein is obtainable from cellular membranes during those stages of development when retina cells are most actively engaged in histological organization. Work in progress indicates that, by the procedures described herein, tissue-specific cell-aggregating factors can also be obtained from membrane preparations of other embryonic tissues.


A potassium ionophore (valinomycin) inhibits lymphocyte proliferation by its effects on the cell membrane. Valinomycin is a depsipeptide antibiotic which selectively translocates potassium across biologic membranes. This potassium ionophore was observed to inhibit phytohemagglutinin-stimulated blastogenesis and proliferation in human lymphocytes. The effect was not due to toxicity to the cells, nor appeared to be due to the effects of valinomycin as an uncoupler of oxidative phosphorylation. Furthermore, the inhibitory effect on phytohemagglutinin stimulated lymphocytes was prevented by increasing the potassium concentration of the external media. These results suggest that the interaction of mitogens with specific receptors at the cell membrane may involve mechanisms affecting cation fluxes and membrane potential. These ionic events may play a role in the transduction of membrane signals for lymphocyte stimulation.


Distribution of calcitonin-sensitive adenylate cyclase activity along the rabbit kidney tubule. The adenylate cyclase [ATP pyrophosphatelyase (cyclizing), EC 4.6.1.1] sensitivity to salmon calcitonin in 11 different segments of the rabbit nephron was investigated using a micromethod for enzyme activity measurements in samples, each containing a single piece of tubule. The required segments were isolated by microdissection from collagenase-treated rabbit kidneys. The results were expressed as femtomoles of adenosine 3':5'-cyclic monophosphate formed per mm of tubular length per 30 min of incubation time. In the presence of 0.1 mug/ml of synthetic salmon calcitonin, it was found that eight segments exhibited no hormonal sensitivity whereas maximal responses were induced in three segments, the "bright" portion of the distal convoluted tubule, the cortical and the medullary portions of the thick ascending limb of the loop of Henle (stimulated over control activity ratios were 32, 11, and27). The very high sensitivity to calcitonin of the adenylate cyclase contained in these three segments (0.01 ng/ml of salmon calcitonin inducing a 2-fold stimulation; half-miximal stimulation corresponding to about 0.3 ng/ml of salmon calcitonin) suggests that the distal convoluted tubule, as well as th cortical and medullary portions of the thick ascending limb of the loop of Henle represent physiological target structures of calcitonin action within the kidney.


Structural heterogeneity of mitochondrial DNA molecules within the genus Drosophila. We have determined by electron microscopy the molecular weight of circular mitochondrial DNA (mtDNA) molecules from 39 species representing 13 groups of five subgenera of the genus Drosophila. mtDNA molecules of all species examined, other than members of the melanogaster group, had, with one exception, molecular weights in the rather narrow range 9.90 X 10(6). The one exception was D. robusta, which had a molecular weight of 10.61 X 10(6). In contrast, mtDNA molecules from species within the melanogaster group had molecular weights covering the considerably greater range 9.92 X 10(6) to 12.35 X 10(6). Applying the electron microscope denaturation mapping technique of Inman to mtDNA molecules of eight species of the melanogaster group, we found each of them to contain a region [presumably rich in adenine and thymine (A+T)] which denatured at a specific temperature (40 degrees) at which most of the remainder of the molecule remained undenatured. The size of the A+T-rich region was constant for mtDNA molecules of a species, but varied from 0.62 X 10(6) to 3.41 X 10(6) for mtDNA molecules of different species. It was demonstrated that the differences in molecular weights of the A+T-rich regions can almost completely account for the differences in total molecular weights of the mtDNA molecules from species of the melanogaster group.


Trimodality in the proportion of hemoglobin G Philadelphia in heterozygotes: evidence for heterogeneity in the number of human alpha chain loci. The extent of variability in the number of human hemoglobin (Hb) alpha chain loci has not yet been conclusively determined. There is evidence that in some populations individuals may possess two alpha-chain loci, while in other populations only one locus is present. Electrophoresis of peripheral blood from 53 heterozygotes for Hb G Philadelphia (alpha 68 Asn leads to Lys) revealed that the proportion of Hb G is trimodally distributed, with modes at approximately 20, 30, and 40% Hb G. Familial, hematologic, and statistical studies suggest that hte proportion of Hb G is not random but is genetically controlled and inversely correlated with mean cell volume. Two alternative genetic models are proposed to explain these findings: one assums alpha-thalassemia, while the other postulates variability in the number of alpha-chain loci in the American Black population. Biosynthetic studies of blood from 15 subjects revealed balanced synthesis of alpha and beta globin chains in heterozygotes from all three classes, strongly supporting variable gene dosage rather than alpha-thalassemia as the mechanism underlying the observed trimodality in the proportion of Hb G. Incompatibilities between out results and current concepts of alpha-thalassemia are discussed in the context of differences between Black compared with Oriental and Italian forms of Hb H disease.


Genetically determined protein polymorphism in the rabbit nervous system. One of the polypeptides (H1) of the rabbit nervous system occurs in an altered form (H2) in some rabbits. The electrophoretic mobility of H2 on sodium dodecyl sulfate-polyacrylamide gels is about 6% greater than that of H1, suggesting that the two polypeptides differ in molecular weight by about 10,000. The alteration is genetically determined since (i) rabbit phenotypes corresponding to all possible genotypes (H1H1, H1H2, H2H2) were present in an outbred population of rabbits, (ii) the frequency of the phenotype corresponding to the heterozygous genotype (H1H2) was smaller in partially inbred rabbit populations than in outbred populations, and (iii) all of the individuals examined from two partially inbred strains (WH/J and X/J) were of the phenotype that would be expected if they were homozygous (H2H2) for the rare allele of the gene. Preliminary evidence indicates that this polymorphic polypeptide is most abundant in the white matter of the nervous systems of several mammalian species, and is distributed with buffers of low ionic strength and centrifuged at 100,000 Xg.


Sex ratio, sex change, and natural selection. We describe the analogy between the theory of natural selection on sex ratio in newborn gonochores (which will not change sex), and on the age of sex change in sequential hermaphrodites (which are all born into one sex and change to the other later on). We also discuss the conditions under which natural selection favors sequential hermaphrodites over gonochores and vice versa. We show that, in a nearly stable population of nearly constant age composition, selection favors a rare mutant if it increases the prospective reproduction of its newborn bearers that are (or while they are) members of one sex by a percentage exceeding the percentage loss to the other sex.


Structural studies on protein products of murine chromosome 17: partial amino acid sequence of an H-2Kb molecule. By use of single internal radiolabels, 17 of the NH2-terminal 27 amino acids of the murine H-2Kb molecule have been assigned. When the amino acid sequence is compared to that of the murine H-2Kk molecule, there is a minimum of six amino acid differences in 19 positions. This high degree of structural diversity confirms, at the level of amino acid sequence, the known polymorphism of the murine H-2 complex. Significant primary str-ctural homology is evident when the murine H-2Kk and H-2Kb sequences are compared to the recently reported partial amino acid sequences of human transplantation antigens. There is modest homology with beta2-mictoglobulin and immunoglobulins, but the available sequence information is insufficient for a satisfactory evaluation of its significance.


Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Ascorbic acid metabolism is associated with a number of mechanisms known to be involved in host resistance to malignant disease. Cancer patients are significantly depleted of ascorbic acid, and in our opinion this demonstrable biochemical characteristic indicates a substantially increased requirement and utilization of this substance to potentiate these various host resistance factors. The results of a clinical trial are presented in which 100 terminal cancer patients were given supplemental ascorbate as part of their routine management. Their progress is compared to that of 1000 similar patients treated identically, but who received no supplemental ascorbate. The mean survival time is more than 4.2 times as great for the ascorbate subjects (more than 210 days) as for the controls (50 days). Analysis of the survival-time curves indicates that deaths occur for about 90% of the ascorbate-treated patients at one-third the rate for the controls and that the other 10% have a much greater survival time, averaging more than 20 times that for the controls. The results clearly indicate that this simple and safe form of medication is of definite value in the treatment of patients with advanced cancer.


Electron microscopic x-ray microanalysis of normal and leukemic human lymphocytes. A comparative study of the elemental content of normal and leukemic cells was undertaken on a few subjects, using electron microscopic x-ray microanalysis. Phosphorus, sulfur, chlorine, calcium, copper, and zinc were detected in intracellular loci. The concentration of some of the above elements appeared to be disease related. In leukemic lymphocytes, the nuclear zinc was significantly lower than that recorded in normal lymphocytes, while the phosphorus was only moderately decreased. This suggests a faulty zinc uptake or binding in leukemic cells. The possible consequences of intracellular zinc deficiency are discussed.


Vitamin A-containing lipocytes and formation of type III collagen in liver injury. Hepatocellular necrosis in carbon tetracholride-induced injury of rats is associated with an accumulation of lipocytes (perisinusoidal cells or Ito cells) containing fat droplets and giving vitamin A fluorescence. In the subsequent formation of connective tissue septa, transitional cells having morphologic characteristics of lipocytes and fibroblasts are abundant and are associated with the appearance of type III collage-. The features suggest that the lipocyte is the precursor of the fibroblasts responsible for parenchymal fibrillogenesis and under these conditions forms type III collagen. The process is a postulated link between hepatocellular necrosis and fibrosis.


An oscillatory neuronal circuit generating a locomotory rhythm. A quartet of interconnected interneurons whose periodic activity appears to generate the traveling body wave of the swimming leech has been identified on each side of segmental ganglia of the ventral nerve cord of Hirudo medicinalis. Theoretical analysis and electronic analog models of the identified intra- and interganglionic synaptic connections of the segmentally iterated interneurons showed that they form an oscillatory network with cycle period and intra-and intersegmental phase relations appropriate for the swimming movement.


RNase sensitivity of an anterior morphogenetic determinant in an insect egg (Smittia sp., Chironomidae, Diptera). In chironomid midges, the development of head and thorax in the embryo requires the function of cytoplasmic determinants localized near the anterior pole of the egg. Experimental inactivation of these determinants causes a dramatic switch in the developmental program of the embryo. Instead of the normal segment pattern, the aberrant pattern "double abdomen" is formed. Head, thorax, and anterior abdominal segments are then replaced by an additional set of posterior abdominal segments joined in mirror image symmetry to the original abdomen. Such double abdomens have been produced, with a maximum yield of 29%, by application of RNase (ribonuclease I, ribonucleate 3'-pyrimidino-oligonucleotidohydrolase, EC 3.1.4.22) to the anterior pole region of the egg. This was achieved by microinjection or puncturing the eggs during submersion in RNase. Control experiments with inactive RNase S fragments reliably proved that double abdomen formation resulted from RNase activity. Neither application of other enzymes to the anterior pole region nor application of RNase to other egg regions produced double abdomens in significant yields. The effects of RNase concentration and stage of development were determined. The data from these and earlier experiments are compatible with the idea that stored cytoplasmic RNP particles act as anterior determinants. Similarities to genetically caused switches in developmental pathways (homeotic mutations) are discussed.


The caecilian ear: further observations. The structure of the ear is examined in two species of caecilians, Ichthyophis glutinosus and I. orthoplicatus, and the sensitivity to aerial sounds is assessed in terms of the electrical potentials of the cochlea. The results are in general agreement with previous reports on other caecilian species.


[The tensile strength of amalgam after 15 minutes]. The authors are mainly interested in the investigation of the tensile strength of a setting amalgam acquired after 15 minutes after the end of the trituration. Knowledge about this property is of interest because generally this moment corresponds with the time that a patient is asked to put the amalgam restoration into contact with the antagonist tooth. In two series of experiments eight commercial amalgam alloys, two different trituration techniques (hand and Silamat mixing machine) as well as two condensation techniques (hand and Bergendal vibrator) were tested. The reslts reveal that the tensile strengths of the different treatment combinations of amalgams prepared from Dispersalloy are significantly much higher than the minimum value of 2 MN/m2 which is required by the new stipulations of the A.D.A. specification n degrees 1. Some amalgams do not satisfy this requirement. Although the influence of the trituration technique as well as that of the condensation technique turns out to be significant, apparently the influence of the amalgam alloy is of much greater importance.


[Radiation therapy and chemotherapy of primary malignant tumors of the bone (author's transl)]. In recent years, cytostatic chemotherapy has been added to the treatment of primary malignant bone tumors. Long-term results are not yet available. Since many of these tumors metastasize through the blood stream, the prognosis has been poor. Now a general improvement in the total number of cures is expected. In osteogenic sarcoma, amputation or exarticulation of the involved extremities is most frequently suggested; one can, however, continue to use preoperative radiotherapy. After 3 or at the most 6 months, amputation is carried out if the patient is free of metastases. Adjuvant chemotherapy should be carried out in every case. The side effects in the irradiated area, however, are considerably increased and, as a result, immediate amputation will become more and more popular. Irradiation of the primary tumor plays a decisive role in Ewing's sarcoma, surgical removal of the tumor does not require radicality at all costs. In reticulosarcoma of the bone, surgical intervention is limited to a biopsy because of high radiosensitivity. Adjuvant chemotherapy should be carried out in every case since a generalization is to be expected in 30% of the patients. The indications for "prophylactic" radiotherapy of the lung and the neurocranium were discussed.


Polarized light microscopy of enamel structure in incisors from newborn infants. Enamel structure in human primary incisors was histologically examined in order to compare the observations with those from recent studies on incipient carious and fluorosed enamel. Ground sections from mandibular incisors of five full-term human infants were examined in polarized light using aqueous media (water, Thoulet's media), alcohols with different refractive indices, and quinoline. Imbibition graphs were made along traverses from the amelodentinal junction (ADJ) to the enamel surface. Quantitative assessments of the birefringence in different media along the traverses indicated a change in the relative volumes of crystallites and surrounding medium with a continuous growth of crystallites toward the ADJ. The influence of organic material is discussed in relation to the differences in calculated form birefringence observed within the specimens. When examined in quinoline, a 30-40-mum-thick surface zone appeared distinct positively birefringent, indicating that the outermost enamel reacted as a molecular sieve. Because of the lower content of minerals the interpretation of this zone differed from that of similar "dark zones" observed in carious and fluorosed enamel.


Fluoride reactions with dental enamel following different forms of fluoride supply. The reactions with dental enamel of NaF as tablets dissolved in different beverages or supplied with NaCl, simulating domestic salt fluoridation, were studied in tests with enamel surfaces and enamel powder. It was confirmed that powdered enamel can react quite differently from enamel surfaces under certain conditions. Enamel surfaces took up much more fluoride (F) from orange juice than from water or milk, and neither the low pH nor the citrate content of the juice increased the formation of unstable CaF2 in the enamel, as judged from a KOH leaching test. The F uptake by enamel surfaces from 0.25 mM NaF in 175 mM NaCl, corresponding to a dish prepared with salt containing 500 parts/106 F, was about 80% greater than from the same NaF concentration in water. This NaCl concentration did not increase the formation of CaF2 in the enamel, as judged from the KOH test, while 350 mM NaCl caused a moderate increase. The investigations support the administration of NaF tablets with orange juice and plans for domestic salt fluoridation.