Linear dimensional changes during setting of two polycarboxylate cements.

The linear dimensional changes of two polycarboxylate cements have been studied. The measurements were performed on specimens placed on a mercury bath, and were started 3 min after commencing the mix. The specimens were allowed to set at 37 degrees C under various environmental humidity. Specimens from one of the polycarboxylate cements (Durelon), were made using both the universal liquid and the thin liquid meant for cementation. The powder/liquid ratios (P/L) were either 2-5 or 1-5.. Specimens from the second cement (Poly-C), were made using the liquid meant for cementation only with a P/L of 1-5. The dimensional changes of Durelon were dependent on the powder/liquid ratio and the environmental humidity during setting. Under dry conditions this cement showed a maximum contraction of 4-60% after 14 days when a high P/L was used and 6-10% when a low P/L was used. After 1 day under wet conditions no significant differences between cements with high and low P/L were registered, and the mean contraction was 1-10%. The dimensional changes of Poly-C were dependent on the environmental humidity, and after 14 days under dry conditions a maximum contraction of 5-50% was registered and after 1 day under wet conditions a contraction of 0-60%. The contraction of the polycarboxylate cements tested in this study started earlier and were in general more pronounced than that observed for a zinc phosphate cement (Oilo, 1975).


The reproducibility of electromyographic recordings of the masseter muscle in humans.

An investigation was undertaken into the reproducibility of electromyograms of masseter muscles in five human subjects. Under standardized conditions, integrated electromyographic recordings were taken during three sessions on each of 5 days. Analysis of variance showed that at the 0-05 probability level the results were reproducible for each subject not only during the same day but also between days.


Early condylectomy to prevent prognathism: a preliminary report.

The effect of bilateral condylectomy in the child with prognathism is described. Reference is made to the anteroposterior growth component of the mandible as measured by peroperative and postoperative cephalometric radiographs. The interruption in the growth of the mandible, coupled with the retropositioning that occurs immediately after the operation, reduces absolute or relative prognathism. Preliminary observation indicates that this prophylaxis does not prevent reformation of the condyle, nor does it result in any clinically discernible change in mandibular movements. Should the condyle reform before body growth is complete, a recommencement of anteroposterior growth in the mandible occurs.


Sensory perception in overdenture patients.

The discussion of overdentures has been confined to their capacity to use abutment teeth to improve neuromuscular control of mandibular movement. Use of overdentures has been favored often because of their mechanical advantages, but seldom because of the sensory role of the retained abutment teeth. Even though the retained teeth may be periodontally diseased, they still may provide sufficient support for the transmission of masticatory pressures and sufficient periodontal ligament receptors to initiate a jaw opening reflex. Whereas conflicting evidence shows that the periodontal nerve receptors play a role in mandibular positional sensibility (proprioception), pressure perception by the periodontal ligament remains a primary stimulus for the jaw opening reflex. Additional investigations will be essential to a complete understanding of the role of the periodontal ligament receptors. However, recognition of the importance of the periodontal ligament receptors to the overdenture patient as a source of sensory input is vital.


Reliability of fully adjustable, articulators using a computerized analysis.

1. Statistical analysis of the graphic data showed no significant difference between the Denar D5A and Hanau 130-21 articulators for the five subjects tested. 2. The average horizontal Gothic arch angle (beta) at incision was 135 degrees. 3. The functional stroke for the subjects was approximately 5 mm. in the incisor region and 2.5 to 3 mm. in each molar region. 4. Both the Denar D5A and Hanau 130-21 articulators adequately reproduced jaw motion for the five subjects tested.


When to glaze--an electron microscope study.

1. A smooth porcelain surface can be obtained by glazing after grinding. There is no need for sanding or polishing with a rubber wheel. 2. A low-fusing glaze gives a slightly smoother surface than a natural glaze. The low-fusing glaze may be added at any stage of polishing, and the results will be the same.


Possible premature degenerative temporomandibular joint disease in violinists.

On occasion, there is danger of TMJ injury from holding the violin in a playing position for long periods of time. A study of a patient with premature degenerative TMJ disease emphasizes the value of a routine occlusal and TMJ examination.


In-service teacher training in removable prosthodontics.

A partial review of educational literature with respect to in-service education has been presented. The design and evaluation of an in-service teacher training or staff development program in removable prosthodontics have been described. Measurement instruments necessary for the program were also included. In such a program, various educational principles and methodology are presented to dental faculty members who, for the most part, have never before had this type of training.


Dental casts made with natural teeth.

A technique has been described for making a dental cast utilizing the patient's natural dentition. This procedure can be used for making a permanent record for any immediate denture patient. The dental cast with natural teeth, rather than stone teeth, has the advantage of serving as an excellent esthetic guide when the immediate denture is to be remade.


A histologic comparison of palatal mucosa before and after wearing complete dentures.

A histologic investigation to study the tissue changes occurring under complete dentures was done. Biopsies were obtained from 40 patients from the area of left side of the hard palate at the first molar region, midway between the median raphe and the residual ridge. The same patients were examined 3 months after placement of well-fitted dentures. Thirty of the 40 patients responded. A second biopsy was taken from the same area on the right side of these patients. On the basis of the microscopic examination, the following conclusions were drawn. 1. The average thickness of the palatal epithelium of edentulous non-denture wearers was 0.222 mm. in the rete peg region. 2. There was a general increase in the thickness of the palatal epithelium following 3 months of wearing complete dentures. 3. The increase in the palatal epithelium was more marked in the rete peg region than in the inter-rete peg region. 4. There was an increase in the thickness of the keratin layer in most patients. 5. No significant changes were found in the granular-cell layer or the prickle-cell layer. 6. The oral mucous membrane responded favorably to well-fitted dentures.


Prosthodontics--Past, present, and future.

1. The geographic areas served by licensed dental mechanics will increase in number and size in the future. 2. There will be increasing difficulties in supplying dental graduates of a high caliber from our faculties of dentistry to serve adequately in the field of prosthodontics. 3. More graduate (postdoctoral) programs will be needed to train dentists to treat difficult prosthetic patients. The need for prosthetic services is still with us and will continue to grow. Only with progressive thought and aggressive action can organized prosthodontics go forward to meet its challenges. A battle is not won on defense alone, for such has been the game plan to date. Currently, dentists have a reasonable way to deliver an important health service to the population at large. However, only with a rapid advancement in the concept of delivery of total prosthodontic care can the best interests of the public be maintained. Finally, the highest standards of practice and ethics must be the guiding principles to any future changes in the delivery of prosthodontic services to the public.


Oral reconstruction for edentulous patients after partial mandibulectomies.

The prosthodontic reconstruction of the patient who has had a partial mandibulectomy is a formidable challenge. A realistic view of the positive and negative factors must be maintained so that unrealistic promises are not made by the prosthodontist and no unfulfilled hopes are left for the patient. Because of the instability of the mandibular denture, the patient's relaxed central position is used as the jaw relationship for setting posterior teeth with flat occlusal surfaces to allow for lateral freedom of mandibular movements.


Preoperative and immediate postoperative obturators.

The prostheses described evolve from preoperative to immediate to transitional, and the distinction between them is not clearly defined. How long the temporary stage should be maintained depends upon the rapidity of healing of the defect and the judgment of the prosthodontist. Usually, healing is complete 3 to 6 months following surgery, and a definitive obturator may then be constructed. Construction, modification, and insertion of preoperative and immediate postoperative obturators for patients after partial and total maxillectomies were discussed. The purpose of an immediate obturator is to shorten the recovery period of the patient and restore speech, deglutition, and appearance as soon as possible after surgery.


Orbital prostheses.

This article presents the steps used in fabricating an orbital prosthesis. Major considerations such as selection of the spectacle frame and the artificial eye, eye alignment, and clay modeling are emphasized to ensure an esthetically acceptable prosthesis. A simple technique for construction of wax templates for fabrication of orbital prostheses in acrylic resin also was described.


The measurement of jaw movement. Part II.

To summarize, the principles and the application of an apparatus have been described which without appreciable physical restraint provides graphic representations of the movements of a point on the mandible in three conventional anatomic planes-sagittal, coronal, and horizontal. The apparatus also provides data which permit an estimation of the magnitude and direction of movement of a point on the jaw during function in relation to time. This information prepares the way for the calculation of the path of the selected point in space, as well as its mean velocity and acceleration.


Articulators in dental education and practice.

This study showed that only a small percentage of students continued to use or prescribe articulators after beginning their practices. Yet many restorative teaching programs have utilized semiadjustable articulators with the intent to stimulate a continued use of the instrument in practice. Perhaps the emphasis of instruction should not be placed upon a certain type of articulator for all restorative dentistry but instead upon the selection of an articulator dependent upon the degree of difficulty encountered with each patient. For example, a simple articulator may be used for simple treatment such as a single full gold crown in an otherwise healthy mouth with physiologic occlusion. This does not obviate the need for properly related master and opposing full-arch casts of high quality. Also, instruction is required which will assure that the new crown does not introduce occlusal interferences in centric relation, the intercuspal position, or laterotrusive and mediotrusive excursions. Emphasis should be taken away from teaching use of only one instrument. It should instead be directed toward an understanding of the basic principles of occlusion, cultivating an ability to differentiate the complexity of treatment, and then selecting an instrument which will provide the most practical and suitable result. An effort should be made to compensate for the instrument's limitations by careful clinical examination and correction.


Severe feeding difficulty in infants with increased pulmonary blood flow.

Three infants with significant left-to-right intracardiac shunts and moderate cardiac disability failed to thrive primarily because of a complete distaste for food. They refused to feed, spat out food introduced into their mouths, and vomited food that reached their stomachs. These severe feeding difficulties were relieved by intracardiac repair, and we conclude that in some unusual instances such feeding disorders constitute the indication for operation.


Amoeboid movement configuration and mitotic indices of lymphoid cells from children with acute lymphoblastic leukaemia.

Bone marrow smears from 21 untreated patients with ALL have been morphologically analysed. There was a positive correlation between the percentages of lymphoid cells with amoeboid movement configuration (AMC) and the mitotic indices. A high proportion of cells with AMC seems to indicate a more favourable prognosis in spite of differences in subsequent treatment. It is suggested that studies of the incidence of AMC may serve as a prognostic tool in ALL.


Combinations of arabinosyl cytosine and 6-thioguanine for treatment of adults with acute leukemia.

The combination of arabinosyl cytosine and 6-thioguanine has been effective for the treatment of acute leukemia. Three schedules of this combination were studied to determine which was most effective, especially in patients who had prior exposure to either or both of these drugs. Sequential and simultaneous 5-day courses of the combination were ineffective. A regimen consisting of a 5-day course of arabinosyl cytosine followed by a 5-day course of 6-thioguanine and another 5-day course of arabinosyl cytosine produced responses in 36% of 25 patients. Seven of the nine patients who responded were refractory to prior therapy with arabinosyl cytosine and 5 were refractory tp prior therapy with 6-mercaptopurine. However, the median duration of response was only six weeks. Four patients developed central nervous system complications and three of these patients died while in complete remission. Major toxicity from all three regiments was myelosuppression. This regimen was about as effective as most other regimens used as secondary therapy in patients with acute myelogenous leukemia, but its toxicity was too great for routine usage.


Clinical and morphological correlations in acute promyelocytic leukemia.

Thirty adults with acute leukemia and greater than 20% bone marrow infiltrate by promyelocytes were studied. Eighteen patients had acute promyelocytic leukemia (APML) as defined by the presence of malignant promyelocytes, and the remaining 12 patients had acute myelocytic leukemia (AML) with an elevated percentage of normal promyelocytes. Malignant promyelocytes were characterized by abundant, abnormal, cytoplasmic granules, by Auer rods in meshwork pattern, and by splinter cytoplasmic granulations and dilatation of the cisternae of endoplasmic reticulum. Patients with APML had, in general, greater than 35% bone marrow infiltrate by promyelocytes. The degree of bone marrow infiltrate by these cells correlated with the clinical status of the patients. Diffuse intravascular coagulation with bleeding occurred in 61% of patients with APML, and the bone marrows of these patients had greater than 50% promyelocytes. No coagulation abnormalities were seen among patients with elevated bone marrow promyelocytes infiltrate and without APML. Coagulation abnormalities in patients with APML were only corrected by controlling the leukemia itself. When this occurred, patients with APML had an excellent rate of complete remission, and the duration of remission and survival were comparable to the results obtained in adults with AML.


Study of leukocyte kinetics in acute myelocytic leukemia utilizing chromium-51.

Leukocyte kinetic studies using chromium-51 were performed in four patients with acute myelocytic leukemia (AML). Intravascular leukocyte survival was prolonged in comparision with granulocyte survival in normal subjects. Significant splenic pooling occurred in three patients, none of whom had splenomegaly. In one patient studied, circulating leukemic cells were shown to return to the bone marrow. The prolongation of intravascular leukocyte survival in AML in relapse, as in chronic myelocytic leukemia, probably depends on several factors including the presence of immature leukemic cells and the recycling of these cells from the spleen and bone marrow.


Remission induction with L-asparaginase, vincristine, and prednisone in children with acute nonlymphoblastic leukemia.

Forty-five children with acute nonlymphoblastic leukemia in relapse received a total of 56 courses of L-asparaginase combined with vincristine and prednisone. The complete remission rate of 40% (12 of 30 trials) in patients resistant to vincristine and prednisone was almost identical to that in children still sensitive to vincristine and prednisone (42%, 11 of 26 trials). The complete remission rate of 38% (14 of 37 exposures) in those children who had not received L-asparaginase previously compared favorably with the complete remission rate in those children who had received prior L-asparaginase (47%, 9 of 19 exposures). Forty-seven of the 56 induction trials were in children with 1 or more remissions and 14 of these were in children with 3 or more prior remissions. Toxicity was minimal.


Acute myelobalstic leukemia and hypercalcemia. A case of probable ectopic parathyroid hormone production.

We studied a patient with acute myeloblastic leukemia, hypercalcemia, hypophosphatemia and inappropriately elevated serum parathyroid hormone levels to define the mechanism of the hypercalcemia. On six occasions during two years, hypercalcemia occurred in conjunction with relapses of leukmia. Each time, serum calcium decreased to normal levels in parallel with reduction of the leukemic mass. During two periods of hypercalcemia, immunoreactive parathyroid hormone values were abnormally high. In addition, hormone was detected in vitro after short-term incubation of the leukemic cells (after 24 hours, the patient's cells produced 129 pg of PTH per milliliter, whereas myeloblasts from a normocalcemic patient with leukemia produced only 33 pg). In freeze-thawing experiments, 39 pg of parathyroid hormone was released form 1 x 108 of the patient's myeloblasts; no hormone was released from the normocalcemia cells. These findings suggest that the hypercalcemia resulted from ectopic parathyroid hormone production by leukemic cells.


Leukemia of BALB/c mice induced by cellfree filtrate from transplantable Thurzo--Svec rat leukemia.

Leukemia was produced in adult BALB/c mice inoculated with cellfree filtrate derived from cells of transplantable Thurzo-Svec rat leukemia. The leukemogenic activity of 20% filtrates was 10(8) ID 50 per ml. Leukemia induced in mice with rat materials was serially transplantable by cellfree filtrates of leukemic tissues and plasma to the same strain of mice.


Myophosphorylase deficiency: two different molecular etiologies.

Two different forms of myophosphorylase deficiency (McArdle's disease) can be distinguished through the presence or absence of the protein subunit corresponding to phosphorylase in muscle extracts analyzed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. Two patients showed a complete absence of the phosphorylase protein subunit, while another patient had an increased quantity of an apparently defective phosphorylase protein subunit. On the basis of these observations, the existence of two distinct subtypes of phosphorylase deficiency can be inferred.


IgA nephropathy: a report on three cases.

Three cases are presented of a recently defined group of patients with renal disease who presented with macroscopic or persisted microscopic haematuria. These patients were found to have deposition of IgA in the glomerulus. They may thus be classified as suffering from an immunologically related glomerulonephritis.


Vitamin C concentration in plasma and leucocytes of men related to age and smoking habit.

Morning plasma and leucocyte vitamin C concentrations were measured in 178 healthy men aged 17-68 years. In the youngest age group (17-29 years), smokers had significantly lower plasma (P less than 0.01) and leucocyte (P less than 0.001) vitamin C levels than non-smokers. With advancing age plasma and leucocyte vitamin C levels of non-smokers appeared to decline. The lower levels in younger smokers did not significantly alter in the later decades. There was no significant difference between the plasma or leucocyte vitamin C levels of smokers and non-smokers in the decade 60-69 years.


Cardiac rupture with false aneurysm after myocardial infarction.

A case of cardiac rupture is reported after myocardial infarction. Leaking blood was contained within the pericardium and a false aneurysm developed. Ten months later this was successfully repaired. The neck of the aneurysm was transected, the defect in the left ventricle closed and saphenous vein bypass grafts were applied to the anterior descending and right coronary arteries. The literature on this subject is briefly reviewed.


Acute glomerulonephritis: the current role of the streptococcus.

Thirty-one patients who presented with acute glomerulonephritis have been reviewed with respect to the involvement of the streptococcus in their disease. The high incidence of the condition and the fact that 76 percent of the patients had evidence of streptococcal infection, as indicated by a raised anti-streptolysin O-titre is discussed.


Family planning in a hospital clinic.

The establishment of a hospital board family planning clinic and the results during its first year of operation are described. Three hundred and fifty-four patients were seen, a third of whom were interested in sterilisation. Only 3 percent presented with infertility and less than 1 percent referred themselves inappropriately. The failure rate in terms of unwanted unplanned pregnancies was 2 percent, and a further 1 percent had socially inconvenient but desired pregnancies. Of those established on contraception 45 percent chose the pill, 34 percent the intra-uterine device and approximately 10 percent each the injection or a barrier method;


Cystic fibrosis in New Zealand: incidence and mortality data.

The incidence of and mortality from cystic fibrosis in New Zealand for the years 1965-1971 have been reviewed. Data were obtained from hospital admission and death records. All of the 171 cases were of European parentage except for one part-Maori child. The minimum incidence of cystic fibrosis in the European population (one in 3185 live births) is comparable with that in other populations of similar background but somewhat lower than that derived by Becroft (1968). The data show that, during the period of the survey, approximately 30 percent of cystic fibrosis suffereres died at less than 12 months of age.


Some health indicators in New Zealand adolescents: The Rotorua Lakes Study 5.

This paper describes and compares health indicators in Maori and European adolescents attending a coeducational secondary school in New Zealand. No important differences were found in certain urinary constituents, haemoglobin or packed cell volume, fasting plasma glucose, serum urea nitrogen, pulse rate, age of menarche, hospital experience or tuberculin test-BCG status.


What the urine contains following athletic competition.

Forty-two of 369 athletes were found to have a positive Occultest on the first urine sample voided following athletic competition. This positive reaction could be due to the presence of either myoglobin or haemoglobin. The Occultest was most often positive in competitors in the longer duration events such as the marathon. Twenty-six of these 42 specimens with a positive Occultest contained over 10 red cells per mm3. The urine samples were also examined for white cells, casts, bacteriuria and the concentration of urea, creatinine, electrolytes and protein. Proteinuria was a frequent finding and increased with the severity of the exertion.


Adrenal venography and sampling in the diagnosis and treatment of primary aldosteronism.

Adrenal venography and adrenal venous blood sampling for aldosterone and cortisol estimations have been attempted in eight patients with primary aldosteronism. The techniques accurately predicted the location of the aldosterone secreting tumour in all six patients in whom an adrenal vein cannulation was possible. The techniques are useful in the surgical management of solitary adrenal adenomas and are important in the choice of optimal therapy for the variety of disorders presenting as primary aldosteronism.


Fluphenazine decanoate maintenance in schizophrenia: a retrospective study.

In a mirror image study of 43 schizophrenic patients long-acting fluphenazine decanoate injections were found to have a significant effect in reducing hospital admissions and length of stay.


Ceroid enteropathy and vitamin E deficiency.

Ceroid (polymerised peroxidised polyunsaturated fatty acids) deposition in the intestine is a result of chronic malabsorption and vitamin E deficiency. This gives the bowel a striking brown colour. Three patients are described with this condition. The macroscopic and microscopic appearances were similar, but the cause of the malabsorption differed. In one patient with polyarteritis there was regression of the pigments with improvement of the malabsorption after treatment with prednisone.


Duodenal biopsy in 75 New Zealand children.

During the past two years, duodenal biopsy has been used freely in a study of diarrhoea and failure to thrive in South Island children. The technique has proved convenient, safe and diagnostically helpful in a high proportion of cases. It has meant that hospital admission has rarely been required. Parents have appreciated the rapid and definite answers, either positive or negative, which have resulted in more rational treatment for their children.


Compliancy in splint-wearing behaviour of patients with rheumatoid arthritis.

Forty-six patients with rheumatoid arthritis affecting their hands were questioned to establish whether or not they complied with the medical specialist's instructions about wearing splints. Only one-third of the patients appeared to comply. A high extraversion score (measured on the EPI questionnnaire) identified half of the patients who did not comply. All patients scored significantly lower then the population norm on the introversion-extraversion dimension, indicating that this dimension may be involved in the psychosomatic aspect of rheumatoid arthritis.


Notified viral hepatitis in New Zealand.

Statistical analysis of notified cases of viral hepatits in New Zealand for an 18-month period is used first to demonstrate and then to consider a geographical gradient across the country with implications warranting further epidemiologic enquiry.


An adult with haemophilus meningitis: case report.

An adult woman was found to have acute pyogenic meningitis caused by Haemophilus influenzae. Recent reports questioning the rarity of this form of adult meningitis are briefly reviewed.


Breast feeding and the community.

The attitudes of different communities to breast feeding are compared. The ways to promote and encourage breast feeding are discussed with particular reference to the benefits of breast feeding to the child, mother, family and the community.


[Acquired posttraumatic deformation of the lens].

6 months after a double perforation of the eye, a dense scar of the vitreous body was observed with the slitlamp. The inferior part of the posterior lens surface was compressed, but no lens opacity could be seen. Such lens deformations are generally produced by tumors and are known since 1930. But it seems that such compressing scars of the vitreous body have never been described.


[Experiences with cryoextraction of the lens from the vitreous body in 123 cases].

In 123 cases of lens luxation the lens was removed from the vitreous by cryoextraction. It was a success in 119 cases, always intracapsular, and in the majority of cases without or only with a minimal loss of vitreous. A vitrectomy or vitreous suction was never necessary. Evaluating these results, one would advise to employ this procedure early before an advanced vitreous destruction may occur.


Retinal red-free light photographs in two congenital conditions: a case of optic hypoplasia and a case of congenital hemianopia.

Two patients with congenital anomalies involving the optic pathways are described. The first case presented a unilateral hypoplastic optic nerve as well as an ipsilateral inferior conus and an elevated disc. The second case showed the features of homonymous hemianopia with sparing of the macula and decreased visual acuity on the side of the affected cerebral hemisphere. Red-free photographs were obtained in both cases. The importance of this old-new investigative tool in completing a neuro-ophthalmological study is stressed.


Cytoenzymology and 3H-thymidine uptake of retro-ocular connective tissue cultures in experimental endocrino-exophthalmos.

The in vitro retro-ocular connective tissue cultures from guinea pigs with endocrine exophthalmos were studied before and after retro-ocular treatment with cortisol and hyaluronidase. Both cortisol and hyaluronidase inhibited the cell proliferation, the cytoenzymic activities of oxydoreductases, the 3H-thymidine uptake, the number of mitoses and the protein content of cultivated cells.


Vascular lesion (arteriovenous aneurysm or haemangioma) of the orbit in a case of chronic granulomatous disease.

A case of arteriovenous aneurysm or congenital arteriovenous haemangioma of the orbit is described in a 5-year-old boy with chronic granulomatous disease. Lipid pigments are demonstrated in endothelial cells as well as in histiocytes and fibrocytes. There appears to be a decreased ability to remove phagocytosed haemosiderin, in addition to the well-known inability of granulocytes, and probably to some extent of histiocytes, to kill phagocytosed bacteria.


Progressive cone dystrophies.

Patients with progressive generalized cone dystrophy often present nystagmus (or strabism) and complain of photophobia, decrease in visual acuity or disturbances in colour perception. The most classic fundus abnormality is the bull's eye maculopathy or a pallor of the optic disc. Minimal macular changes are sometimes seen, which may progress to a bull's eye type of macular degeneration. The photopic ERG is always very affected, whereas at first the scotopic ERG seems normal. Progressive deterioration of the visual functions is accompanied by increasing fundus lesions and rod involvement, as suggested by the modifications of the dark adaptation curve and the scotopic ERG. However, the progression of typical generalized cone dysfunction is very slow. On the contrary, in some cases of so-called Stargardt's disease with peripheral participation, a very rapid progression has been observed. In such cases a normal ERG does not necessarily mean that the disease will remain localized to the macular area. No definite prognosis can be made on one single ERG. In 3 cases with sector pigmentary retinopathy the photopic ERG was more affected than the scotopic ERG. However, these cases are probably primary cone-rod dystrophies. Although there is no electrophysiological control, our clinical impression is that the evolution, if possible, is very slow.


Time lapse by diagnosis of oral cancer.

This survey comprised thirty-four patients who were suffering from malignant tumors of the oral cavity diagnosed in a 12-year period in the Department of Oral Surgery, Royal Dental College, Aarhus, Denmark. The categories of tumors were as follows: carcinomas (twenty-seven), osteosarcomas (four), reticulum-cell sarcomas (two), and lymphosarcomas (one). Special emphasis is placed upon the calculation of two time factors, i.e., the time that elapsed from when the symptoms were first noticed until the patient consulted a physician or dentist, and the period during which the patient was under professional care up to the time at which a final diagnosis was made. The first of these periods was found to be, on an average, 4.9 months; the second period averaged 5.6 months. The most common complaints were swelling and pain, two symptoms with which the physician or surgeon often are confronted. This may be a possible reason for a relatively late diagnosis in the case of several malignant tumors. A frequently very suspect symptom, such as a persistent ulceration, was found in only thirteen of twenty-seven cases of carcinoma, whereas another symptom in the same category, disturbances in sensibility, was noted in only three cases. Because of the short observation period in some cases, no correlation between the two time factors and the prognosis was attempted. Despite the inadequacy, it may be concluded that the period of 5.6 months which in this material was found to elapse between the first consultation and the actual time of diagnosis was far too long. All lesions that do not respond to adequate therapy in 14 days should be suspected of being malignant, and the patient should be referred to a specialist for proper diagnosis.


Fracture of the styloid process of the temporal bone: an unusual complication of dental treatment. Report of a case.

Reported in a case of fracture of the styloid process due to an uncoordinated action of the suprahyoidean and infrahyoidean musculature. The similarity of symptoms to acute disturbances of the temporomandibular joints to those of fracture of the styloid process and the differential diagnoses are discussed. Diagnosis of a fracture of the styloid process is achieved mainly by radiographic examination; history and clinical examination are merely confirmatory. Conservative and surgical treatments of fracture of the styloid process, and their respective uses, are briefly reviewed.


Idiopathic failure of eruption of permanent molar teeth.

Failure of permanent teeth to erupt without any known cause is a seldom occurring phenomenon. However, it brings to light our ignorance of the basic physiologic mechanism of tooth eruption. In this article we present five patients with unerupted permanent molar teeth. In all instances, no obvious cause exists. Indications for operative intervention and management are discussed, but the cases are also presented to focus attention on our lack of knowledge of the physiology of tooth eruption.


The solitary bone cyst. Report of two cases.

Two cases of solitary bone cyst are described. Case 1 is interesting in that the age of presentation was near the extreme lower end of the range of recorded cases, and also the site was in the mandibular ramus, extending to the sigmoid notch, which is one of the least common sites in this bone. Furthermore, the lesion was not clinically silent; 26 per cent of Howe's series had swelling with or without pain, and 24 per cent of Huebner's and Turlington's series. Cases 2 illustrates the value of radiographs which give a general view of the mandible and maxilla, since this particular lesion was quite unexpected. Although the etiology is still dispute, the treatment by surgical intervention is almost universally agreed upon.


Resorption and regeneration of alveolar bone in acute osteomyelitis of the mandible.

A 12-year-old boy developed osteomyelitis of the anterior part of the mandible subsequent to a blow on the mouth. The condition resulted in loosening of the lower incisors and considerable loss of alveolar bone. Under conservative treatment the condition subsided and the bone regenerated completely. Radiographs taken at various stages in the treatment show the loss of bone and its gradual regeneration.


Reduction of malodor by oral cleansing procedures.

Organoleptic and gas chromatographic methods were employed to establish the threshold of odor objectionability of methylmercaptan and hydrogen sulfide and to assess the relative effectiveness of different oral hygiene measures to reduce the malodor to acceptable levels. The study showed that methylmercaptan and hydrogen sulfide concentrations below 0.5 ng. and 1.5 ng., respectively, are considered nonobjectionable. Gas chromatographic analyses indicate that these concentrations were exceeded in the early morning mouth air samples of approximately 50 per cent of the adult population studied. In these instances, methylmercaptan and hydrogen sulfide occurred in sufficiently high concentrations to account for the malodor. Brushing studies suggest that the early morning malodor arising from the oral cavity can be controlled by proper oral hygiene. The tongue was the major source of both offending compounds in the persons studied. Methods that involved cleansing of the dorsoposterior surface of the tongue caused the most pronounced reductions of both compounds. Since methylmercaptan was found to be more objectionable and to exhibit a lower threshold of objectionability, it was more difficult to reduce to acceptable levels.


Bacterial endocarditis. Survey of patients treated between 1963 and 1975.

Hospital records of forty-nine patients with a diagnosis of bacterial endocarditis at the University of Kentucky Medical Center Hospital from 1963 to 1975 were reviewed. Data collected and statistically analyzed resulted in the following conclusions: 1. Bacterial endocarditis affected males three to four times as often as females. 2. Morbidity was significant, with an average hospital stay of 4 weeks. 3. The mortality rate among the entire group of patients was 42.8 per cent. A significantly higher rate of 66.7 per cent was noted in patients with prosthetic heart valves. 4. The most prevalent predisposing factor was rheumatic heart disease. 5. There were five cases (10.2 per cent) in which dental procedures were the probable precipitating cause, once again pointing out the importance of detecting susceptible patients and proceeding with dental therapy only after adequate prophylactic measures. 6. The most frequently isolated microorganism was Staphylococcus aureus. 7. Chloramphenicol was the most effective in vitro antiboitic tested, with erythromycin a close second. Although it might appear that penicillin was not as effective, the concentration in actual usage may differ significantly from that in the tested discs. Penicillin, therefore, still remains the foundation for treatment in susceptible cases.


The labial melanotic macule.

Fifty-five cases of a melanotic lesion of the lips which is well known, but not well described, are reported. The lesions characteristically occur on the lower lips of young adults. Males and females are equally affected. These lesions may be ephelides, postinflammatory melanoses, or unique lesions for which there is no exact cutaneous counterpart. We suggest the term labial melanotic macule as a descriptive one which would encompass the three different constituent entities. On the basis of follow-up information obtained and the histopathologic character of the lesions, this entity is benign and does not, in our opinion, have any malignant potential.


Ultrastructural study of an odontogenic myxoma.

Ultrastructural study of an odontogenic myxoma has revealed two basic types of tumor cells: secretory and nonsecretory. The secretory cell type is the principal tumor cell and resembles the fibroblast in many respects. Although the ultrastructural findings indicate an abortive attempt at collagen fibrillogenesis, there is at the same time prominent secretory activity within the tumor cells, resulting in excessive production of acid mucopolysaccharide ground substance. There may also be phagocytosis by tumor cells of residual collagen in the area compatible with an odontogenic origin, they are not incompatible with an origin from primitive nonodonotogenic mesenchymal rests.


The oral cavity as a source of potential pathogens in focal infection.

The various microbial species present in different areas of the oral cavity are described. A few streptococcal species, whose only known habitat is the mouth, have been associated with subacute bacterial endocarditis, and it would therefore seem that the oral cavity can serve as a reservoir for at least one type of focal infection. However, the role of oral bacteria in other types of focal infection is obscure.


A study of the resolution of dental films and screens.

From the study of the resolution produced by 156 screen-film combinations at a film density between 1.41 and 1.59, the following conclusions are drawn: 1. Resolution is affected by screens, films, and observers. 2. The effect of screens on resolution is much greater than the effect of films. 3. Screens varied greatly in resolving ability. 4. Films did not differ greatly in resolving ability. 5. Cronex Lightning Plus screen and Radelin super high-speed screen produced the lowest resolution and Cronex detail screen produced the highest resolution. 6. In general, the slower the screen, the higher is the resolution and vice versa. 7. There were two groups of films with significant resolution differences. 8. Films designed to be processed automatically did not differ significantly in their resolving ability when processed manually. 9. There is significant interaction effect of screens and films on resolution. 10. Individual visual resolving ability plays a significant role in measuring resolution.


Mechanisms for the involvement of high molecular weight kininogen in surface-dependent reactions of Hageman factor.

The mechanisms by which human high molecular weight kininogen (HMKrK) contributes to the surface-dependent activation of the Hageman factor systems have been studied. The ability of various mixtures of purified human Hageman factor (coagulation factor XII), HMrK, prekallikrein, and kaolin to activate coagulation factor XI was determined with factor XIa (activated factor XI) clotting assays. Hageman factor, HMrK and prekallikrein were required for maximal rates of activation of factor XI. A certain optimal mixture of purified Hageman factor, HMrK, prekallikrein, and kaolin gave the same rapid initial rate of activation of purified factor XI as an equivalent aliquot of factor XI-deficient plasma. This suggests that potent, surface-mediated activation of factor XI in plasma is explicable in terms of Hageman factor, HMrK, and prekallikrein. By studying separately some of the surface-dependent reactions involving Hageman factor, it was found that HMrK accelerated by at least an order of magnitude the following reactions: (i) the activation of factor XI by activated Hageman factor; (ii) the activation of prekallikrein by activated Hageman factor; and (iii) the activation of Hageman factor by kallikrein. Stoichiometric rather than catalytic amounts of HMrK gave optimal activation of factor XI. These results are consistent with the hypothesis that HMrK and Hageman factor form a complex on kaolin which renders Hageman factor more susceptible to proteolytic activation by kallikrein and which facilitates the action of activated Hageman factor on its substrate proteins, factor XI and prekallikrein.


Evidence for regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and cholesterol synthesis in nonhepatic tissues of rat.

The adenine analogue 4-aminopyrazolopyrimidine has been reported previously to reduce the hepatic secretion of plasma lipoproteins in rats, thereby lowering the plasma cholesterol level. In the current studies, reduction of the plasma cholesterol level by 90% in rats through the administration of aminopyrazolopyrimidine was found to be associated with a 5- to 30-fold increase in the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase [mevalonate:NADP+ oxidoreductase (CoA-acylating), EC1.1.1.34] in kidney and lung. In both tissues, the enhanced activity of this microsomal enzyme was associated with a 3-fold elevation in the rate of cholesterol synthesis from either [14C]acetate or [14C]octanoate. Comparable increases were not observed in the activities of several other microsomal enzymes or in the rates of [14C]acetate incorporation into saponifiable lipids or CO2. When administration of 4-aminopyrazolopyrimidine was terminated, plasma cholesterol levels rose and 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity declined in the kidney in a reciprocal manner. These data are consistent with the hypothesis that the low levels of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity and cholesterol synthesis that are normally observed in certain nonhepatic tissues of the rat are due to an active form of feedback regulation mediated by cholesterol carried in plasma lipoproteins.


BCG immunotherapy in chronic myelocytic leukemia.

In 16 patients with chronic myelocytic leukemia an attempt to retard the myeoblastic transformation was carried out by means of repeated BCG administration in the period of remissions resulting from chemotherapy. Vaccinations were repeated at intervals of 4 weeks with doses of 2 mg of Mycobacteria by scarification. The time of uninterrupted remissions maintained with BCG vaccinations only ranged from 2 to 28 months, on the average 7.4 months. In this group 2 patients died and the duration of follow-up in the remaining cases ranges from 16 to 106 months, average 43.5 months. The survival time in the group of 16 patients with the same disease, who died after treatment with cytostatics only, was shorter ranging from 12 to 83 months, 32 months on the average. In one patient BCG vaccination was followed by tuberculosis of a supraclavicular lymph node.


Biosynthesis of lipid-linked oligosaccharides and glycoprotein in aorta: stimulation by acceptor lipids isolated from liver.

An acidic glycolipid fraction was isolated from porcine liver and partially purified on DEAE-cellulose. This material markedly stimulated the incorporation of mannose from GDP-[14C]mannose into lipid-linked oligosaccharides and into glycoprotein, but did not stimulate incorporation into the mannosyl-phosphoryl-polyprenol. The products formed from GDP-[14C]mannose in the presence of acceptor lipid were a series of lipid-linked oligosaccharides of mannose and N-acetylglucosamine (GlcNAc) which differ from each other in the size of the oligosaccharide moieties. The acceptor lipid fraction was partially characterized in terms of its carbohydrate composition by mild acid hydrolysis and reduction with NaB3H4. The [3H]sugars were then separated into a number of monosaccharides and oligosaccharides by paper chromatography. Strong acid hydrolysis of two of the larger oligosaccharides released from the acceptor lipid followed by reduction with NaB3H4 gave [3H]mannitol and [3H]GlcN-ol in ratios of 2.8:2 and 3.8:2, indicating that these compounds probably were penta- and hexasaccharides. In addition, GlcNAc was shown to be at the reducing terminus and alpha-linked mannose at the nonreducing ends of the molecules. The results suggest that the acceptor lipid fraction is composed of oligosaccharides of (Man)n leads to GlcNAc leads to GlcNAc, probably attached to a polyprenol through a pyrophosphoryl linkage.


Fetal membrane collagens: identification of two new collagen alpha chains.

Human fetal membranes contain two new genetically distinct collagen polypeptide chains which are subunits of one (or two) new molecular species of collagen. These new polypeptide chains, which we have tentatively named alphaA and alphaB, have been directly compared with the polypeptide chain subunits of Types I, II, and III human collagen and Type IV collagen from bovine lens capsule. Both alphaA and alphaB exhibit characteristic profiles on carboxymethyl-cellulose chromatography and sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The distribution of methionine residues along both new chains is different from known collagen chains as manifest by distinctly different cyanogen bromide peptide profiles on carboxymethyl-cellulose chromatography and/or sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Both alphaA and alphaB exhibit contents of amino acids and glycine typical of collagens, and comparison with the observed and reported compositions of collagen chains of Types I-IV collagens reveals notable differences, particularly in the content of alanine, leucine, isoleucine, and the basic amino acids, lysine, hydroxylysine, and arginine. The new collagen species containing both alphaA and alphaB may be separated in the native (triple-helical) state from other native collagen species by differential salt precipitation. The observations that both chains coprecipitate in the same narrow NaCl range, and that the ratio of alphaA:alphaB is constant, suggest the possibility of a single new species of collagen with a subunit structure alphaA [alphaB]2.


Purification and characterization of two initiation factors required for maximal activity of a highly fractionated globin mRNA translation system.

Two additional initiation factors (IF-M4 and IF-M5) have been purified and characterized both physically and biologically. IF-M4 is active as a single polypeptide chain with a molecular weight of 48,000. In contrast, IF-M5 is active as a complex with a molecular weight of about 500,000 and consists of seven major and several minor polypeptide components. Analysis of IF-M5 in two polyacrylamide gel electrophoresis systems indicated that one of the major polypeptide chains of IF-M5 was the 35,000 dalton subunit of IF-MP. This analysis also revealed that IF-M2A, IF-M3, and elongation factor 2 were present as minor components. Both IF-M4 and IF-M5 are required to achieve maximal activity in an assay system dependent on exogenous globin mRNA, but neither factor has been observed to stimulate model reactions that utilize artificial templates [poly(U) or AUG].


Preliminary analysis of 1H and 13C spectral and relaxation behavior in methionine-enkephalin.

Nuclear magnetic resonance studies on the conformational dynamics of the pentapeptide H-Tyr-Gly-Gly-Phe-Met-OH are reported. This peptide, for which the generic trivial name "methionine-enkephalin" has been suggested, is pharmacologically active as a ligand for the mammalian opiate receptor(s). The studies reported are parallel investigations in two solvents (dimethylsulfoxide and water) of: 1H and 13C high resolution spectral assignments; 1H and 13C spin-lattice relaxation times, temperature dependence of amide proton chemical shifts, and half-times for chemical exchange or amide protons. From these data we conclude that the tyrosine side chain of methionine-enkephalin exhibits restricted motion with respect to the main peptide backbone of the molecule. On the other hand both the phenylalanyl and methionyl side chains are undergoing intramolecular reorientation with relatively high frequency.


Enzymatic conversion of benzo(a)pyrene leading predominantly to the diol-epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene through a single enantiomer of r-7, t-8-dihydroxy-7,8-dihydrobenzo(a)pyrene.

Benzo(a)pyrene is metabolically and stereospecifically converted by mixed-function oxidases of rat liver microsomes and epoxide hydratase (glycol hydro-lyase (epoxide-forming), EC 4.2.1.63)to the single enantiomer (-)r-7,t-8-dihydroxy-7,8-dihydrobenzol (A) pyrene. This enantiomer is further metabolized stereoselectively by the mixed-function oxidases to predominantly the diol-epoxide, r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzol(a)pyrene in which the 7-hydroxyl and the 9,10-epoxide are trans. Other unidentified metabolites are also formed from the r-7,t-8-dihydroxy-7,8-dihydrobenzo(a)pyrene. Racemic r-7,t-8-dihydroxy-7,8-dihydrobenzo(a)-pyrene is converted metabolically to both r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene and r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene. The diol-epoxides are unstable in aqueous medium, and their identification and characterization as r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene and r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene were accomplished by the identity of their tetrahydroxytetrahydrobenzo(a)pyrenes hydrolysis products with those of the authentic synthetic compounds with respect to mobility on high-pressure liquid chromatography and mass and ultraviolet absorption spectral analysis. The diol-epoxides were also reduced in the presence of NADPH to distinct trihydroxypentahydrobenzo(a)pyrenes. Since the synthetic racemic r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene is very highly mutagenic in mammalian cells, we suggest that it is the metabolically formed diol-epoxide that may be an ultimate carcinogenic form of benzo(a)pyrene.


Short-lived methylated messenger RNA in mouse kidney.

In experiments originally designed to examine selective turnover of methylated "caps" in renal mRNA, we observed that [3H]methyl label decayed from mRNA containing poly(A) with a half-life of 1-2 hr. (Caps are blocked, methylated mRNA sequences of the general structure m7GpppNm p(1 or 2)Np.). To distinguish between metabolism of short-lived mRNA and discriminate turnover of "caps", we compared residual [3H]methyl label in 5' and 3'mRNA fragments prepared from mRNA isolated during the decay period. Hydrolysis of mRNA at 0 degrees with dilute KOH before oligo(dT)-cellulose selection produced 5' mRNA fragments enriched with an alkali-resistant oligonucleotide with a -5 charge; the 3' mRNA fraction was correspondingly reduced in oligonucleotide content. Since methyl label disappeared at the same rate from both fractions, we conclude that mouse kidney contains short-lived mRNA and that the "caps" of these labile mRNAs turn over with the rest of the mRNA molecule.


Photoaffinity labeling and quaternary structure of the acetylcholine receptor from Torpedo californica.

Membrane fragments from electric tissue of Torpedo californica containing nicotinic acetylcholine receptor are composed of four different polypeptide chains with molecular weights of 40,000 (alpha), 48,000 (beta), 62,000 (gamma), and 66,000 (delta). The alpha and beta chains are still present in all and gamma and delta in some of the receptor preparations after Triton X-100 extraction and purification by affinity chromatography. All components of the receptor react covalently with the photoaffinity label 4-azido-2-nitrobenzyltrimethylammonium fluoroborate, the delta chain incorporating less of the reagent as compared to the alpha and beta chains. Agonists and antagonists containing a quaternary ammonium group protect all chains against the label; the principal neurotoxin from Naja naja siamensis protects the alpha chain only. We conclude that the alpha chain binds the neurotoxin from Naja naja, the alpha and beta chains are involved in the binding of ligands with quaternary ammonium groups, and the function of the gamma and delta chains remains to be determined.


Detection of different types of damage in alkylated DNA by means of human corrective endonuclease (correndonuclease).

Corrective endonuclease (correndunclease) activity of HeLa cells was assayed with alkylated DNA. Double-stranded, covalently closed DNA from phage PM II was treated with methyl methanesulfonate, N-methyl-N-nitrosourea, beta-propiolactone, or diepoxybutane to introduce alkylated bases and alkali-labile sites into the DNA. The damaged DNA was incubated with an extract of HeLa cells that catalyzes the formation of breaks at apurinic sites in double-stranded DNA. Methylated DNA was broken at every alkali-labile site by the HeLa correndonuclease, which indicated that these sites are similar to the apurinic sites produced by heating at acid pH. DNA alkylated with beta-propiolactone or diepoxybutane containing the same number of alkali-labile sites was broken to a far lesser extent. This indicates the presence of a second type of alkali-labile damage that is correndonuclease-insensitive.


Linking numbers and nucleosomes.

In considering supercoils formed by closed double-stranded molecules of DNA certain mathematical concepts, such as the linking number and the twist, are needed. The meaning of these for a closed ribbon is explained and also that of the writhing number of a closed curve. Some simple examples are given, some of which may be relevant to the structure of chromatin.


Electron microscopy of DNA crosslinked with trimethylpsoralen: test of the secondary structure of eukaryotic inverted repeat sequences.

It has been suggested that inverted repeat (palindrome) sequences, which are widespread in eukaryotic genomes, exist in two alternate configurations, a linear form and a cruciform. To investigate the relative frequency of these forms, the DNA of intact mouse tissue culture cells was covalently crosslinked with 4,5',8-trimethylpsoralen (me3-psoralen) in order to prevent rearrangement of the DNA secondary structure during DNA isolation. The distribution of me3-psoralen crosslinks was determined by electron microscopy after denaturation of the DNA in the presence of glyoxal. Because of the high frequency and the relatively uniform distribution of the me3-psoralen crosslinks, it could be concluded that almost all of the inverted repeat sequences had been crosslinked. In spite of this, no significant number of cruciforms was detected by electron microscopy. To determine whether the me3-psoralen might itself be disrupting cruciform structures, cruciforms were first produced in isolated Tetrahymena rDNA by heat treatment and then crosslinked in vitro. The crosslinking was found to stabilize rather than disrupt these cruciforms. We conclude that the inverted repeat sequences of the mouse tissue culture cells we tested are predominantly in linear forms rather than in cruciform structures inside the cell.


Psoralen-crosslinked secondary structure map of single-stranded virus DNA.

The photochemical crosslinking of DNA by 4,5',8-trimethylpsoralen (trioxsalen) has been used to freeze the secondary structures of single-stranded DNA molecules of bacteriophage fd at different ionic strengths. These secondary structures (hairpins or looped hairpins) have been visualized in the electron microscope. Most of the single-stranded circular fd DNA molecules show only one hairpin after irradiation at 15 degrees in 20 mM NaCl in the presence of trioxsalen. As the ionic strength is increased, more hairpins appear on the DNA molecules. To map these secondary structures, double-stranded supercoiled fd DNA (RFI) was cleaved with the restriction enzyme HindII, which makes only one cut on each RFI molecule. After denaturation and crosslinking of the linear single-stranded fd DNA (a mixture of viral and complementary strands), all the hairpins have been mapped on the DNA molecule with respect to this HindII site. The results show that these hairpins occur at specific sites. The most stable hairpin has been assigned to the position where the initiation site for the conversion of single-stranded fd DNA to the double-stranded covalently closed form has been mapped. The remaining hairpins map in or near regions corresponding to in vitro promoter sites on the fd DNA.


Chemical characterization of the selenoprotein component of clostridial glycine reductase: identification of selenocysteine as the organoselenium moiety.

A small, heat-stable selenoprotein, one of the components of the glycine reductase complex, was labeled with 75Se by growth of Clostridium sticklandii in the presence of Na2 75SeO3. The selenium-containing moiety, which is essential for the biological activity of the protein, was shown to be a selenocysteine residue. It was isolated as its Se-carboxymethyl, Se-carboxyethyl, and Se-aminoethyl derivatives from digests of the pure 75Se-labeled protein that had been reduced and treated with the various alkylating agents prior to hydrolysis. In each instance the 75Se-labeled moiety obtained from an alkylated protein sample and the corresponding alkyl derivative of authentic selenocysteine were indistinguishable. Several studies of the native selenoprotein detected a chromophore (UVmax 238nm) that appeared upon reduction of the protein with KBH4 and rapidly disappeared upon exposure to oxygen. This oxygen-labile chromophore is thought to be the ionized -SeH group of the selenocysteine residue.


Mechanism of action of beta-bungarotoxin on synaptosomal preparations.

The neurochemical activity of beta-bungarotoxin was investigated using a synaptosomal preparation of rat cerebral cortices. In preparations preincubated with [3H]choline in order to label acetylcholine the toxin caused a rapid release of the transmitter, which was calcium dependent but only a little affected by a depolarizing concentration of potassium. beta-Bungarotoxin was also shown to be a potent inhibitor of the high affinity transport system for choline, producing 50% inhibition at a concentration of 50 nM. These findings explain the observed electrophysiological effects of the toxin. Electron microscopy revealed no discernible effect of 0.1 muM beta-bungarotoxin on either synaptic vesicles or mitochondria. Neither the release of transmitter nor the inhibition of choline uptake by the toxin was affected by the presence of an inhibitor of phospholipase activity.


Isolation and characterization of the protein coded by gene A of bacteriophage phiX174 DNA.

Replication of phiX174 circular replicative form (RFI) DNA by extracts of Escherichia coli infected with bacteriophage phiX174 (amber in gene A) requires the phiX174 gene A product. This requirement has been used as an assay for the isolation of this protein. The gene A product (purified 4000-fold) caused relaxation of superhelical phiX174 RFI and formation of discontinuities in the viral strand of phiX174 RFI uniquely situated in the A region of the genome, and yielded a complex after interacting with phiX174 RFI that is active in replication of phiX RFI.


(+/-)-7alpha,8beta-dihydroxy-9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo(a)-pyrene is an intermediate in the metabolism and binding to DNA of benzo(a)pyrene.

The addition of borate buffer to the aqueous methanol used to elute hydrocarbon-deoxyribonucleoside derivatives from an LH 20 Sephadex column resulted in the separation of the products of reaction with DNA of the stereoisomers, (+/-)7alpha,8beta-dihydroxy-9alpha,10alpha-epoxy- and (+/-)-7alpha,8beta-dihydroxy-9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrenes, i.e., the syn- and anti-benzo(a)pyrene-diolepoxide, respecitvely. By this technique it was shown that the microsome-mediated binding to DNA of benzo(a)pyrene-7,8-dihydrodiol involved exclusively the anti-benzo(a)pyrene-diolepoxide. The benzo(a)pyrene binding to DNA that resulted on exposure of BHK21/C13 cells to this carcinogen was also shown to result predominantly by reaction of the anti-benzo(a)pyrene-diolepoxide. However, in this case other derivatives, including the syn-benzo(a)pyrene diolepoxide, might also be involved.


Membrane potential dependent binding of scorpion toxin to action potential Na+ ionophore.

Depolarization of neuroblastoma cells causes a 70-fold increase in the apparent dissociation constant KD for scorpion toxin enhancement of activation of the action potential Na+ ionophore by veratridine and a large increase in the rate of reversal of scorpion toxin action. Depolarization also inhibits binding of 125I-labeled scorpion toxin to a small number of saturable binding sites on electrically excitable neuroblastoma cells and increases the rate of dissociation of scorpion toxin from these sites. The results suggest that scorpion toxin binds to a regulatory component of the action potential Na+ ionophore whose conformation changes on depolarization.


Structural (shape-maintaining) role of the cell surface glycoprotein of Halobacterium salinarium.

The obligate halophile, Halobacterium salinarium, maintains a rod-shaped morphology under normal growth conditions. Lactoperoxidase(EC 1.11.1.7;donor:hydrogen-peroxide oxidoreductase)-catalyzed iodination and treatment with proteolytic enzymes were used to demonstrate that the recently described envelope glycoprotein (Mescher, M.F. & Strominger, J.L. (1976) J. Biol. Chem. 251, 2005-2014) is the only major cell surface component of this organism. The morphological changes that accompany alteration of the structure of the glycoprotein by growth in the presence of bacitracin or its removal with proteolytic enzymes strongly suggest that it forms a rigid matrix at the cell surface and is responsible for maintenance of the characteristic rod shape.


1,N6-etheno-AMP and 1,N6-etheno-2'-deoxy-AMP as probes of the activator site of glycogen phosphorylase from rabbit skeletal muscle.

Both 1,N6-etheno-AMP and 1,N6-etheno-2'-deoxy-AMP bind at the AMP site of phosphorylase b (1,4-alpha-D-glucan:orthophosphate alpha-glucosyltransferase, EC 2.4.1.1). Etheno-AMP induces the same activation as AMP, about 30-fold higher than the activation induced by etheno-dAMP. The fluorescence of etheno-AMP and etheno-dAMP is associated with the base moiety; therefore, when free in solution, the two derivatives have identical fluorescence properties. However, when bound to phosphorylase, the fluorescence of etheno-AMP is quenched more efficiently than the fluorescence of etheno-dAMP. This difference between the fluorescence properties of the bound nucleotides suggests that a modification in the ribose ring affects the position of the adenine in the AMP site of phosphorylase b. The observed quenching may be due to a stacking interaction between an aromatic residue and the base moiety of the bound nucleotide.


Control of renal vitamin D hydroxylases in birds by sex hormones.

Kidney homogenates from adult male Japanese quail or chickens demonstrate hydroxylase activity predominantly for the 24 rather than the 1 position of 25-hydroxyvitamin D3 (25-hydroxycholecalciferol). A single injection of 5 mg of estradiol-17beta into a male bird completely suppresses the 24-hydroxylase and greatly increases the 1-hydroxylase activity. Immature males do not respond well to estrogen alone, but they do respond well to estradiol plus testosterone. Testosterone alone has little or no effect on the hydroxylases of either species. Castrated male chickens show an estradiol response only when testosterone is also given. Optimal 24 hr responses to 5 mg of estradiol per kg in the castrate male were obtained with about 12 mg of testosterone per kg. These optimal amounts of estradiol and testosterone increased the activity of 25-hydroxyvitamin D3-1-hydroxylase approximately 225-fold (this enzyme is also known as 25-hydroxycholecalciferol 1-monooxygenase; 25-hydroxycholecalciferol, NADPH: oxygen oxidoreductase (hydroxylating), EC 1.14.13.13). These results demonstrate a strong regulation by the sex hormones of the renal vitamin D hydroxylases in birds.


Direct spectroscopic observation of inner and outer hydrocarbon chains of lipid bilayer vesicles.

Distearoylphosphatidylcholines labeled with gem-difluoro groups at selected positions of the fatty acid chains have been prepared. These lipids were incorporated into sonicated vesicles and were examined by fluorine nuclear magnetic resonance spectroscopy. All spectra are characterized by two well-separated fluorine resonances. Paramagnetic ions added to the exterior solution of vesicles of fluorinated lipid broaden the upfield resonances, whereas ions trapped in the vesicles interior broaden the downfield resonances. This demonstrates that the fluorine chemical shift of these compounds is sensitive to differences between the inner and outer monolayers of sonicated vesicles.


Regulation of protein synthesis in rabbit reticulocyte lysates: characteristics of inhibition of protein synthesis by a translational inhibitor from heme-deficient lysates and its relationship to the initiation factor which binds Met-tRNAf.

In heme-deficient reticulocyte lysates a translational inhibitor which regulates protein synthesis is formed or activated. To define the mechanism of action of the translational inhibitor (RI), RI was partially purified. We have utilized the isolated RI to examine its relationship to the translational inhibitor formed in situ in heme-deficiency, some quantitative aspects of inhibition of protein synthesis, and the relationship of RI concentration to the initiation factor (IF-MP) which forms a ternary complex with Met-tRNAf and GTP (IF-MP-Met-tRNAf-GTP). The results demonstrate that the activity of isolated RI is related to the in situ heme-deficiency inhibitor by several criteria: (a) the biphasic kinetics of inhibition manifested by RI in lysates containing optimal levels of hemin are very similar to those observed in heme-deficiency, i.e., an initial period in which several rounds of protein synthesis proceed at the control rate followed by an abrupt decline in the rate of protein synthesis. (b) Both inhibitions are accompanied by the disaggreagation of polyribosomes with a concomitant increase in 80S ribosomes. (c) Both inhibitions are reversed by IF-MP. The isolated RI blocked protein synthesis in lysates at temperatures ranging from 15 degrees to 30 degrees. Although the rate of protein synthesis was a function of the temperature of incubation, the number of rounds of protein synthesis prior to shut-off was essentially the same at various temperatures. When RI was added to lysates, at increasing intervals after the start of incubation, the period of synthesis before shut-off (lag) progressively decreased. The inhibition of protein synthesis by RI was immediately reversed by the addition of IF-MP. The extent of reversal increased with increasing concentrations of IF-MP; at low levels of RI almost complete reversal of inhibition by IF-MP was obtained. However, at high levels of RI which did not appreciably increase the degree of inhibition of protein synthesis, equivalent amounts of IF-MP were less effective in reversing inhibition. These results suggest that the inhibition of protein synthesis by the isolated inhibitor involves the initiation factor IF-MP.


Detection of mRNA sequences in nuclear 30S ribonucleoprotein subcomplexes.

RNA from nuclear 30S ribonucleoprotein (RNP) complexes of mouse ascites cells has been shows to contain sequences homologous to poly(A) + mRNA by its ability to hybridize with complementary DNA prepared from poly(A) + mRNA template. Analysis of the hybridization kinetics of poly(A) + mRNA with its own complementary DNA revealed several abundancy classes. The total complexity of poly(A) + mRNA from ascites cells was estimated to be approximately 30,000 sequences of average molecular weight (6 X 10(5)). When the hybridization reaction of 30S RNP-RNA with mRNA-specific cDNA was compared to the homologous reaction the majority, and most probably all, of the poly(A) + mRNA sequences were found to be present in the RNA. The kinetics of hybridization suggest that 10-15% of the RNA in this RNP complex is homologous to poly(A) + mRNA. The 30S RNP subcomplexes therefore contain nuclear poly(A) + mRNA sequences as well as the bulk of heterogeneous RNA.


Thermodynamic fluctuations in protein molecules.

Apparently conflicting views of the physical nature of globular proteins, and other macromolecules, may be reconciled by consideration of the inevitable thermodynamic fluctuations inherent in microscopic systems. Discrete protein molecules, considered singly, undergo sizeable fluctuations in thermodynamic properties which are manifest in their stochastic properties. This is not incompatible with time-averaged studies of ensembles of proteins from which a more compact, rigid, and static view of these molecules may be obtained.


Bacteriophage T3 and T7 early RNAs are translated by eukaryotic 80S ribosomes: active phage T3 coded S-adenosylmethionine cleaving enzyme is synthesized.

RNA transcribed in vitro from the early region of bacteriophage T3 or T7 was translated by cytoplasmic ribosomes which synthesized protein in cell-free systems prepared from mammalian cells and wheat germ. The proteins synthesized in vitro and their counterparts prepared from infected Escherichia coli comigrate by polyacrylamide gel electrophoresis with sodium dodecyl sulfate and are similarly affected by deletion or amber bacteriophage mutations. Bacteriophage T3 codes for an enzyme that cleaves S-adenosylmethionine and this activity was detected among the products of the mammalian cell-free system. Bacteriophage T3 or T7 RNA, after endoribonuclease III (EC 3.1.4.24) cleavage, gave higher levels of incorporation into phage T3 or T7 polypeptides than when an equivalent amount of the uncleaved RNA was added to the eukaryotic cell-free systems. Methylation of phage T3 or T7 RNAs is apparently not required for translation in either the wheat germ or mammalian cell-free system. The ability of T3 and T7 RNA to be translated in the presence of saturating amounts of natural eukaryotic mRNAs suggests that many prokaryotic genes introduced into mammalian cells might be expressed if they were transcribed in an appropriate form.


Defective thymine dimer excision by cell-free extracts of xeroderma pigmentosum cells.

Crude extracts of normal human diploid fibroblasts and of human peripheral blood lymphocytes excise thymine dimers from purified ultraviolet-irradiated DNA, or from the DNA presumably present as chromatin in unfractionated cell-free preparations of cells that had been labeled with [3H]thymidine. Extracts of xeroderma pigmentosum cells from complementation groups A, C, and D also excise thymine dimers from purified DNA, but extracts of group A cells do not excise dimers from the DNA of radioactively labeled unfractionated cell-free preparations.


Inhibition of erythrocyte phosphate transport by high pressures.

Pressures of 200-1000 atmospheres (20-100 MPa) are found to decrease significantly the amount of phosphate (H32PO4-2)transported into the rabbit erythrocyte under otherwise physiological conditions. Such compression does not cause irreversible morphological changes or result in membrane disruption. The findings are interpreted in terms of a lipid phase transition induced by the high pressure, which is propagated to the associated phosphate transport system by a physical mechanism.


Quantitation of delta-crystallin messenger RNA during lens induction in chick embryos.

Embryonic chick cells of the presumptive lens ectoderm are induced to differentiate into a lens by the optic vesicle, an outgrowth from the developing brain. This lens induction involves formation of the lens placode by cell elongation between about 44 and 50 hr of development, followed by invagination of the placode between about 50 and 55 hr of development. The amount of delta-crystallin messenger RNA (mRNA) in heads of embryos between 48 and 72 hr of development was determined by molecular hybridization with [3H]DNA complementary to purified delta-crystallin mRNA. An average of approximately 0.5 pg of delta-crystallin mRNA was found per embryonic head at 48 hr of development. This leads to approximately 265 molecules of delta-crystallin mRNA per lens cell, if one assumes that the mRNA is confined to the lens rudiment, as is indicated by immunofluorescence studies of delta-crystallin performed by other investigators. Pulse-labeling experiments with [35S]methionine indicated that the delta-crystallin mRNA is being translated already at this time. delta-Crystallin mRNA accumulated at an average rate of 1 molecule per cell per minute between 48 and 72 hr of development. Thus, by extrapolation, the initiation of delta-crystallin mRNA accumulation coincides with the initiation of lens placode formation at approximately 43-44 hr of development, which is some 8-9 hr after the initiation of lens induction by the optic vesicle. These data suggest that delta-crystallin synthesis is regulated by the accumulation of delta-crystallin mRNA during lens induction in chick embryos.


Polycation-induced assembly of purified tubulin.

Several different polycations have been found that can substitute for the microtubule-associated proteins, or tau factor, in facilitating assembly of tubulin that has been purified by ion exchange chromatography. In low concentrations of the polycation diethylaminoethyl-dextran, 7 mg of tubulin is pelleted per 1 mg of polycation added. Under conditions favorable to microtubule assembly the entire pellet is seen by electron microscopy to consist of "double wall microtubules", which are essentially identical to normal microtubules in subunit structure and arrangement. When assembly is inhibited approximately the same amount of tubulin is pelleted, but it is in the form of clusters of curved sheets or filaments apparently related to tubulin rings. When conditions are changed to favor assembly, the tubulin within these clusters appears to reassemble to form the double wall microtubules.


Decreased fidelity of DNA polymerase activity isolated from aging human fibroblasts.

DNA polymerase (deoxynucleosidetriphosphate: DNA nucleotidyltransferase, EC 2.7.7.7 or DNA nucleotidyltransferase) activity, isolated from late and early passage cells of the diploid human fibroblast line, MRC-5, was compared. The level of activity dropped with increasing passage. In addition, when the fidelity of polymerization was monitored with four synthetic templates under a variety of conditions, it was observed that the enzyme from late passage cells was more error-prone. The possible relation of these observations to "senescence" of the fibroblasts is discussed.


Interrelationship of hexosaminidases A and B: conformation of the common and the unique subunit theory.

Human kidney hexosaminidase A (beta-N-acetylglucosaminidase; 2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase; EC 3.2.1.30) is a heteropolymer of two immunologically distinct subunits designated as alpha and beta. Hexosaminidase B, however, is a homopolymer comprised entirely of beta subunits. When human kidney hexosaminidase A was dissociated into its subunits by p-hydroxymercuribenzoate, three distinct proteins having isoelectric points of pH 7.2.5.4, and 4.3 were isolated. The fraction having an isoelectric point of pH 7.2, designated as beta fraction, was electrophoretically and immunologically identical to hexosaminidase B and was enzymatically active. The proteins having isoelectric points of pH 5.4 and 4.3, designated as hexosaminidase Ai and alpha fractions, respectively, were enzymatically inactive and crossreacted with antiserum against hexosaminidase A and not with antiserum against hexosaminidase B. Upon incubation of p-hydroxymercuribenzoate-treated hexosaminidase A with dithiothreitol,, hexosaminidase A activity, as well as antigenicity, was regenerated, indicating that alpha and beta subunits hybridize to form hexosaminidase A. Antibodies raised in rabbits against beta fractions reacted with both hexosaminidase A and B, whereas the antibodies against alpha and hexosaminidase Ai fractions reacted only against hexosaminidase A. This would indicate that both fractions are composed only of subunits unique to hexosaminidase A. The molecular weights of alpha,beta, and hexosaminidase Ai fractions were estimated to be 47,000, 120,000, and 180,000 respectively, by Sephadex gel filtration. Upon urea-sodium dodecyl sulfate polyacrylamide electrophoresis, each of the three fractions dissociated into a single polypeptide having a molecular weight of approximately 18,000. It is concluded that p-hydroxymercuribenzoate dissociates hexosaminidase A, (alphabeta)3, into its subunits, and the beta subunits can reassociate to form relatively stable hexosaminidase B, (betabeta)3, while the alpha subunits reassociate in both the dimeric state, alpha2, and a polymeric state, alpha8.


Chromosome-mediated gene transfer between closely realted strains of cultured mouse cells.

Gene transfer between two closely related mouse cell lines has been carried out, using as the vector a cell-free preparation of metaphase chromosomes and nuclei. Distinction between gene transferents and revertants of the recipient mutant phenotype was achieved by the use of a donor strain carrying a mutationally altered (8-azaguanine-resistant) hypoxanthine-guanine phosphoribosyltransferase (HPRTase; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8). The transferred HPRTase gene is initially unstable; in nonselective medium, it is lost at a rate of about 0.1 per cell per generation. Stabilization occurs as a rare event, with a frequency on the order of 1 X 10(-5) per cell per generation. The unstable state can be maintained for at least 200 generations through serial passages of the transferent in selective medium. Under the conditions of cultivation used in these experiments, the unstable HPRTase-positive cells are eventually replaced by the stable HPRTase-positive cells in the population.


Radiation-induced mutations at mouse hemoglobin loci.

In experiments designed to detect new mutations affecting hemoglobin, we irradiated the male or female parent in reciprocal crosses of two mouse strains that differ in alleles at the hemoglobin (Hba, Hbb) loci as well as at five other specific loci. Offspring were analyzed for hemoglobin properties (electrophoretic pattern, solubility, crystal pattern), serum albumin differences, erythrocyte lysis, reticulocyte count, and external appearance. Five hemoglobin variants were found among the mutants. In three, the genetic contribution from the irradiated father was not expressed with regard to the alpha-chain; one carried a tandem deuplication (the first known case in the mouse) involving Hbb; and one probably resulted from double nondisjunction of chromosome 7. The finding that major chromosome aberrations can mimic hemoglobin mutations indicates the need, in similar experiments, to follow F1 screening with thorough cytogenetic analysis. The variants in which there is nonexpression of the alpha chain may be the result of small deficiencies or of faults in transcription or translation. Mutation rates based on these three variants are not out of line with earlier specific-locus results, although confidence limits are still wide.


Radioimmunoassay for intact Gross mouse leukemia virus.

A radioimmunoassay for intact Gross leukemia virus has been developed using 125I-labeled Gross virus grown in tissue culture and guinea pig antisera to Gross virus grown either in tissue culture or harvested from leukemic C3H(f) mice. Separation of bound from free labeled virus was effected using the double antibody method. The assay can detect fewer than 10(8) virus particles and has been used to measure the viral content of individual organs from inoculated leukemic C3H(f) mice and from Ak mice with spontaneous leukemia. Organs from noninoculated healthy C3H(f) mice crossreacted poorly in the system, virus generally being detectable only in the thymus and spleen and at low concentration. In some of the inoculated C3H(f) leukemic mice the viral content of as little as 0.5 mul of plasma is measurable. That this assay is for intact virus and not for soluble antigens of the viral envelope was proven by the observation that the immunoreactive material of plasma and extracts from thymus and liver of leukemic mice has a buoyant denisty in sucrose of 1.17-1.18 g/ml, corresponding to that of intact virus grown in tissue culture. With this sensitivity it may now be possible to quantitate viral concentrations in tissue and body fluids from the time of inoculation through the development of obvious pathology.


Increased ion permeability of planar lipid bilayer membranes after treatment with the C5b-9 cytolytic attack mechanism of complement.

The ion permeability of planar lipid bilayers, as measured electrically, was found to increase modestly upon treatment with purified complement complex C5b,6 and complement components C7 and C8. The subsequent addition C9 greatly amplified this change. No permeability changes occurred when components were added individually to the membrane, or when they were used in paired combinations, or when C5b, C7, C8, and C9 were admixed prior to addition. Thus, there is a significant parallel between the permeability changes induced in the model membrane and damage produced in biological membranes by the C5b-9 complement attack sequence. The efficiency of membrane action by C5b-9 was critically dependent on the order in whcih components were added to the membrane. There were also differences in the electrical properties of membranes treated with C5b-8 and C5b-9, though in both cases the enhanced bilayer permeability is best attributed to the formation of trans-membrane channels. Collectively, the data are consistent with the hypothesis that the mechanism of membrane action by complement involves the production of a stable channel across the lipid bilayer, resulting in cell death by colloid-osmotic lysis.


Purine metabolism in adenosine deaminase deficiency.

Purine and pyrimidine metabolites were measured in erythrocytes, plasma, and urine of a 5-month-old infant with adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) deficiency. Adenosine and adenine were measured using newly devised ion exchange separation techniques and a sensitive fluorescence assay. Plasma adenosine levels were increased, whereas adenosine was normal in erythrocytes and not detectable in urine. Increased amounts of adenine were found in erythrocytes and urine as well as in the plasma. Erythrocyte adenosine 5'-monophosphate and adenosine diphosphate concentrations were normal, but adenosine triphosphate content was greatly elevated. Because of the possibility of pyrimidine starvation, pyrimidine nucleotides (pyrimidine coenzymes) in erythrocytes and orotic acid in urine were measured. Pyrimidine nucleotide concentrations were normal, while orotic acid was not detected. These studies suggest that the immune deficiency associated with adenosine deaminase deficiency may be related to increased amounts of adenine, adenosine, or adenine nucleotides.


Experimental myasthenia in Balb/c mice immunized with rat acetylcholine receptor from rat denervated muscle.

A new model of an autoimmune disease of the neuromuscular junction was obtained by injection of acetylcholine receptor purified from rat denervated muscles into Balb/c mice. Anti-rat, then anti-mouse acetylcholine receptor antibodies, appear in mouse serum during the immunization procedure. Electrophysiological investigations performed on immunized mice reveal a neuromuscular block similar to that found in myasthenia gravis. Not a single mouse with objective signs of muscular weakness was lacking anti-mouse acetylcholine receptor antibodies but no correlation was found between their level and the severity of the disease.


Nonsuppressible insulin-like activity and thyroid hormones: major pituitary-dependent sulfation factors for chick embryo cartilage.

Serum from hypothyroid hypophysectomized rats did not stimulate sulfation or incorporation of amino acids into chick embryo sterna. When such rats were treated for a short time with growth hormone (somatotropin), their serum stimulated incorporation both of sulfate and of amino acids. The different actions of the two types of sera were not due to changes in thyroid state. The results support the existence in serum of a sulfation factor for chick embryo cartilage that is dependent upon growth hormone. Highly purified preparations of nonsuppressible insulin-like activity from human serum stimulated incorporation of amino acids, and of uridine into RNA, in chick embryo sterna in vitro; chondrocytes prepared from this tissue had specific high-affinity binding sites for this insulin-like activity. However, sulfate incorporation was stimulated very little, unless serum from hypothyroid hypophysectomized rats was also present. When L-3,5,3'-triiodothyronine was added as well, the stimulation was enhanced further. From these and other experiments, we conclude that (i) nonsuppressible insulin-like activity or a closely related peptide is the growth-hormone-dependent growth and sulfation factor for chick embryo cartilage: (ii) a second, unidentified factor must be present for the insulin-like activity to stimulate sulfation; and (iii) stimulation of sulfation by thyroid hormones in vitro is additive to that of nonsuppressible insulin-like activity.


Diphenylhydantoin (dilantin) gingival hyperplasia: drug-induced abnormality of connective tissue.

Various degrees of gingival overgrowth may occur in individuals taking diphenylhydantoin, a drug used widely in the treatment of epilepsy. The tissue overgrowth is made up predominantly of collagen, and may therefore be a useful model for analysis of fibrosis and some other connective tissue abnormalities. Fibroblasts derived from the overgrown tissue exhibit a level of protein synthetic activity approximately twice that of comparable cells obtained from nonepileptic control individuals and from the gingiva of age-matched epileptics taking the drug but not exhibiting gingival enlargement. In addition, 20% of the protein synthesized by cells from the affected tissue is collagen, whereas collagen accounts for only about 11% of the total protein produced by control cells of both types. The drug appears to induce or select for fibroblasts characterized by enhanced levels of protein synthesis and collagen production. This alteration persists through several cell replications in vitro in the absence of drug.


Circadian organization of the estrous cycle of the golden hamster.

In constant dim illumination the hamster estrous cycle free-runs with a period that is a quadruple multiple of the concurrently recorded rhythm of wheel-running activity; both activity and estrous cycles are generated by biological clocks. Maintenance of stable phase angle differences between heat onset and running onset before and after treatment with deuterium oxide suggests that a common circadian system generates periodicities in estrus and activity. An organization of the estrous cycle is proposed in which the stimulus for the ovulatory surge of luteinizing hormone is generated by a circadian system that includes the suprachiasmatic nuclei of the hypothalamus. Various possible interactions of estradiol and photoperiod with the neurogenic stimulus for the luteinizing hormone surge are described and implications of different types of circadian organization of the estrous cycle for theories of sexual differentiation are considered.


Effects of persistent selective suppression of ganglionic butyrylcholinesterase on steady state and regenerating levels of acetylcholinesterase: implications regarding function of butyrylcholinesterase and regulation of protein synthesis.

Persistent selective suppression of the butyrylcholinesterase (cholinesterase; acylcholine acyl-hydrolase, EC 3.1.1.8) activity of the superior cervical, stellate, and ciliary ganglia of cats by the daily administration of tetramonoisopropyl pyrophosphortetramide, 3.0 mumol/kg, intravenously, for 6 days produced a significant elevation in the levels of ganglionic acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7). When the same procedure was preceded by the inactivation of over 95% of the ganglionic acetylcholinesterase by sarin, 2.0 mumol/kg, intravenously, the rate of regeneration of acetylcholinesterase was decreased. Results are interpreted as evidence that ganglionic butyrylcholinesterase may serve as a precursor to acetylcholinesterase, and that the level of butyrylcholinesterase may regulate the rate of acetylcholinesterase synthesis.


Cyanoacrylate as an adhesive for other medicaments: a study with triamcinalone on the healing of experimental oral ulcers.

This study was undertaken to determine whether cyanoacrylate can be used to adhere other medicaments to oral ulcers in the hope of promoting healing. Triamcinalone was chosen since it is used presently in pastes in the oral cavity. Sixty rats were dived into three equal groups. In each animal under anesthesia with ether, bilateral equivalent ulcers, 2 mm in depth and diameter, were made with the tip of a rongeur on the midlateral aspect of the tongue. The right side served as a control. The left side was experimental and received the following: group I--isobutyl-2-cyanoacrylate only; group II--powdered triamcinalone acetonide; group III--triamcinalone covered with cyanoacrylate. All materials were reapplied every 24 hours for 4 days. Two animals from each group (6) were sacrificed at 1, 4, and 8 hours and 1, 2, 3, 5, 14, and 21 days. The results indicate that a powdered medicament can be held in place on oral ulcers for at least 24 hours. The ulcers with cyanoacrylate revealed less edema and cellular response for up to 24 hours. Healing of the ulcers was neither promoted nor delayed in any group.


Saliva stimulation in dogs with permanent duct fistulae.

Saliva fluids were collected from catheters inserted in the duct openings of permanent paratid and sublingual duct fistulae prepared in dogs. In anesthetized dogs stimulants applied to the tongue had no effect on saliva output. In awake dogs topically applied sucrose (1.25%-20%) had no significant stimulating effect on salivary secertion when compared to water control responses. Citric acid (1.25%-20%), applied topically, resulted in dose-related fluid increases, with parotid volumes consistently higher than sublingual volumes. Pilocarpine (0.125 mg/kg, IV), elicited similar saliva volumes in awake and anesthetized animals; sublingual secretions were higher than parotid volumes. For comparing drug secretion or saliva composition in awake and anesthetized animals, use of the same, preferable an IV, stimulant administered on a milligram perper-kilogram basis is suggested.


11beta-hydroxysteroid dehydrogenase in subcellular particulates of rat submandibular salivary gland.

11beta-hydroxysteroid dehydrogenase (11beta-HSD) was studied in intracellular components of the rat submandibular salivary gland. The difficulty in retaining 11beta-HSD activity during fractionation was overcome by using soybean trypsin inhibitor. Relatively pure subcellular particles were obtained by altering the initial centrifugal speeds used for the various fractions. 11beta-HSD was found to have its main activity in the crude nuclear fraction of the gland. Pure nuclei were isolated by centrifuging the crude nuclear fraction through 1.8-M sucrose at high speed, and these were found to retain the major enzyme activity. It was hypothesized that 11beta-HSD may influence genetic expression processes in salivary gland, but further work will have to be undertaken to investigate this possibility.


Lead health hazard in root calan filling material.

It has been stated in the recent literature that the lead content of N2 endodontic filling material poses a hazard of lead otxicity to the patient. No clinical evidence in humans was offered in support of the statements. In the studies here reported, it was determined that endodontic fillings of RC2B, A U.S. variant of the N2 material, contain, per root-canal, a quantity of lead equivalent to permissible uptake of 10-15 days. It is believed lead is generally unavailable to the blood stream, due primarily to its being chemically bound, and secondarily to the known affinity of dentin for lead. It was found that the levels of lead in the blood of nine young male patients, sampled at intervals up to 90 days following placement of RC2B endodontic fillings, were mostly nondetectable, did not exceed 9 mug/100 ml in any instance, and were all far below the accepted hazard-indicating level of 40 mug/100 ml whole blood.


Biological active peptides in human urine: III. Inhibitors of the growth of human leukemia, osteosarcoma, and HeLa cells.

Medium-sized peptides isolated from normal humans urine were tested for their effect on DNA, RNA, and protein synthesis, and mitosis, in tissue culture of human myeloblastic leukemia, osteosarcoma, and HeLa cells. Two types of antineoplastic peptides were found. One type consists of strongly acidic peptides (probably sulfated glycopeptides) which act specifically on different kinds of neoplasma. The other type comprises slightly acidic and neutral peptides, and has broad specificity. The active peptides produce up to 97% inhibition of DNA synthesis and mitosis in the neoplastic cells in tissue culture. The peptide fraction which has broad specificity was tested in different concentrations and gave good dose-response relationship.


Ventilator-related extra-alveolar air in adults.

Extra-alveolar air (EAA) developed in 38 patients during mechanical ventilation. High ventilatory pressures and destructive lung disease predispose to EAA. Pneumoretroperitoneum and pneumoperitoneum are more common forms of ventilator-induced EAA in adults than generally realized; an associated pneumomediastinum was always identified when one of the two disorders above resulted from ventilation. Retroperitoneal air was located laterally along the liver and in the flanks, and changed little with change in patient position. Early detection of EAA may allow life-saving changes in therapy to be implemented.


Occlusal adjustment by grinding of teeth; indications and techniques.

Occlusal adjustment by grinding of teeth is a therapy that all dentist can master, provided they base it on a knowledge of what constitutes an acceptable occlusion. There is hardly use for intricate or difficult rules and prescriptions for occlusal adjustment. After having diagnosed the occlusal condition in the patient, the dentist has to decide how to attain the goal : an acceptable occlusion without interferences, that is tooth substance that is in the way of harmonious function. Very often simple grinding of teeth can improve the occlusion of our patients. And in combination with other corrective measures, e.g. prosthetic rehabilitation and orthodontic treatment, occlusal adjustment by grinding deserves to be used much more frequently in clinical dentistry than it is today. It is a cheap and simple procedure that can improve our patient's occlusal hygiene. And occlusal hygiene is a concept that now should be incorporated in odontology as oral hygiene seems to have been universally accepted. And we dentists are even more responsible for increasing the quality of occlusion in our patients than we are for the standard of their oral hygiene.