Clinical signs for the early recognition of cancer of the oral cavity.

The dentist bears a particularly great responsibility with regard to the early detection of cancer of the oral cavity, since only early detection provides the greatest prospect of a cure. A description is therefore given of the features of the oral mucous membrane on which the differential diagnosis of 'carcinoma of the oral cavity' must in particular be made. The author then sets out an examination procedure which every dentist should follow before any treatment is given; this will also make it possible to detect those carcinomas of which the patient himself is not yet aware.


Epidemiological studies of oral cancer.

The FDI has shown considerable interest in the oral cancer and has in recent years arranged three symposia on the subject. The incidence of oral cancer shows marked geographic differences mostly depending upon environmental factors. In the present paper the epidemiology of oral cancer is illustrated by the relative frequency to total number of cancers and incidence rates from a number of countries. Canada has the highest rate of cancer of the vermilion border, which is extremely rare among dark-skinned people. Even within one country differences may be found, a fact which is illustrated by findings from Czechoslovakia and India. In most of the studies dealing with the etiology of oral cancer tobacco usage in its various forms is shown to be the outstanding factor.


Dental education in Sénégal.

At the present time Senegal has two types of dental education: a full university training for dentists and a training programme for operating dental auxiliaries. The teaching objectives of the Institute of Dentistry and Stomatology were defined in such a way that these two grades work together in a public health team trained in accordance with the general principles of a common education in preventive and social dentistry. This dental education system which has received the full support of WHO and is backed by the educational and hess in all the African countries which send students for training in Dakar. This success is undoubtedly due to the fact that the system is designed to train personnel adapted to the special problems found in Africa, with a realistic approach to local conditions, and capable of providing effective help for the African communities whose dental health needs have for too long been neglected.


Teaching clinical judgment in periodontics.

Clinical judgment is a complex process that is difficult to develop. It is the essence of the health professional, yet most dental curricula do not emphasize the learning of the judgmental process. In this paper the judgmental process is analyzed into three components: input, mediation, and output. Following the analysis, suggestions for using these components are presented in four instructional phases: the introductory phase, the initial guidance phase, the application phase, and the feedback phase. While the illustrations used are drawn from periodontics, the principles are generalizable to the teaching of all clinical disciplines.


The oral-facial geneticist: his training and role in dentistry.

There is a great need today for clinical geneticists who can diagnose hereditary malformation complexes and counsel afflicted patients and their families. The vast majority of these heritable syndromes have significant expression in the oral-craniofacial complex. This paper describes the minimal qualifications and training needed by postgraduate dentists to function as oral-facial geneticists. The oral-facial geneticist is defined as a human geneticist who has special interest and training in diseases of the oral-facial complex. In addition to patient care and consultation, persons with such training may make important contributions to teaching and research in cranio-facial growth and development.


A survey of human genetics in the dental school curriculum.

A survey of American dental schools was conducted to determine the extent to which genetics is currently taught. Results indicate that there is a stronger emphasis at the postdoctoral level than at the predoctoral level and that the approach to teaching genetics tends to multidisciplinary. Some dental schools have already given organizational status to genetics and have instituted clinical activities in orofacial or craniofacial genetics. Considerable interest was shown in audiovisual materials and autotutorial programs in genetics. A greater emphasis on the teaching of genetics at the predoctoral, postdoctoral, and continuing education level is recommended. More trained orofacial geneticists are needed to support didactic and clinical activities within the dental schools.


Genetics in the postdoctoral dental curriculum.

Over the past decade, genetics has played an increasingly important role in both predoctoral and postdoctoral dental programs. In an effort to define the scope of genetics education at the postdoctoral level, this paper outlines desired learning objectives and presents a curriculum model which has proven effective in meeting these objectives.


Correlation between preclinical and clinical grades.

This study indicated that grades for preclinical performance in the restorative laboratory were seldom predictive of the same student's performance in the clinic and should be used very carefully by promotions committees in evaluating a student's potential for success.


Teaching physical evaluation and physical diagnosis in a hospital setting.

The inclusion of physical evaluation as a predoctoral course emphasizes the physical and emotional needs of the patient to the dental student. The dental graduate who enters a general practice residency program will have better preparation for his hospital training and he will have more time to develop diagnostic skills if his predoctoral training includes physical evaluation.


Dental aspects of patients with cystic fibrosis: a preliminary clinical study.

The oral conditions of 42 patients being treated for cystic fibrosis were evaluated. The patients were grouped by age and, in some aspects, were compared with a small control group of their siblings. The patient group had a lowered incidence of plaque and less gingival disease than did the control group in which every person had some amount of plaque or gingival disease. Calculus formation was minimal. The reasons for the finding of minimal plaque in the patient group could be related to several factors, including the life-long use of various antibiotic agents, the chewing of digestive enzyme supplements, the effect of medical management on tooth hardness, and the effect of stained teeth (possible tetracycline deposition) on the plaque microorganisms. It appears that the therapy for cystic fibrosis was beneficial to the periodontal health of these patients. Much further study is needed to understand the interrelationship between an altered oral environment (salivary changes in cystic fibrosis), altered microbial flora (by antibiotics, enzymes) and even altered tooth surfaces (possible tetracycline deposition). Most patients were found to have one or more oral habits. Tooth mobility was associated with tension habits. Patients who had clubbed fingers (indicating pulmonary compromise) and possibly a severe disease process, did not appear to have either stained teeth or the severity of the gingivitis associated with this. The relationship of tetracycline to tooth staining could not be pinpointed.


Apparent viscosity of materials used for making edentulous impressions.

The viscosity of commercially available impression materials used for making edentulous impressions was determined as a function of time and rotational speed. The impression materials studied showed large differences in viscosity and could be ranked into three groups. The values for one group--Plastogum, Ackerman cement (1:1 powder-to-liquid ratio), and light-bodied Permlastic--ranged from 23,800 cp to 57,200 cp. The viscosity values for a second group--Unilastic, syringe Elasticon, Luralite, and Coe-Flo--ranged from 92,200 cp to 107,000 cp. For a third group--Omniflex, Jeltrate, and Ackerman cement (2:1 powder-to-liquid ratio)--the viscosity values ranged from 239,000 cp to 257,000 cp. Light-bodied Permlastic, Ackerman cement (1:1 powder-to-liquid ratio), Jeltrate, and syringe Elasticon functioned as Newtonian liquids immediately after mixing. All other materials were non-Newtonian in behavior. The viscosity of most impression materials increased dramatically with time; the only exceptions were the zinc oxide-eugenol impression materials.


Citric acid consumption and the human dentition.

The habitual and abusive use of fruits and foods containing citric acid can cause serious dissolution effects on human tooth enamel. Because these effects can occur so easily, this paper suggests that foods and fruits containing citric acid, as well as other acids, could be definite contributors to the many other forms of idiopathic erosion so often observed by the dentist. There is a need for continued research and study in this area.


Character and frequency of discomfort immediately following restorative procedures.

Within 24 hours after dental treatment, discomfort was experienced by 78% of the patients questioned. Sensitivity to cold was the most frequent type of discomfort experienced (reported by 50% of the patients). Postoperative discomfort resulting from cold stimulus was most often mild (in 78%), occasionally moderate (in 22%), and never severe. The duration of postoperative discomfort resulting from cold stimulus was most often fleeting (reported by 94%) and seldom prolonged (reported by 6%). The second most frequent type of postoperative discomfort reported was associated with the administration of the local anesthetic. Sensitivity to sweets does not seem to be a source of postoperative discomfort following routine operative dental procedures.


Endodontic perforations: their prognosis and treatment.

Causes of tooth perforation include resorption, caries, and operator performance. The prognosis for a tooth with a perforation is related to the location of the perforation, negotiability of the canal, contamination, and treatment. Alternative treatment approaches include routine endodontic treatment, correction via the chamber, surgical correction, and stimulation of calcification. In most instances, a perforation can be treated so that satisfactory healing will occur.


Failure of hand disinfection with frequent hand washing: a need for prolonged field studies.

In a prolonged field trial a 4% chlorhexidine digluconate detergent scrub (Hibiscrub(R)), that had earlier proved to be an effective hand disinfectant, was studied in hospital wards. Finger tips were found to harbour more bacteria than the hand dorsum and the samples collected from them yielded more information on the bacteriological and dermatological effects of hand disinfectants in practice.In wards with a relatively low hand-washing frequency (less than 20 times in 8 hours) the bacteriological results resembled those obtained by in-use tests with volunteers. In the neonatal unit where the hand washing frequency was remarkably high, even occasionally over 100 times/8 h shift, an increase in the bacterial colony counts of the majority of the staff was recorded both before and after hand washing already after using the preparation for 1 week. Age, occupation and hand-washing frequency all correlated with the bacteriological results. Twenty-seven out of 37 persons complained of side effects such as wounds of finger tips and redness or heavy drying of the skin. Wounds, particularly on finger tips, resulted in the failure of disinfection. An increase in bacterial counts was sometimes noted without any dermatological or subjective changes. Drying of the skin was complained of less often when no increase in skin bacteria occurred.After the changeover of washing practice to a detergent followed by a rinse with spirit solution containing chlorhexidine and glycerol a decrease was recorded in the bacterial counts. It is concluded that more attention should be paid to long-term testing of hand washing and disinfection methods to ensure optimum final results in practice. It is obvious that the knowledge obtained from short time in-use testing cannot be applied to all conditions of use.


Bacterial contamination in a modern operating suite. 1. Effect of ventilation on airborne bacteria and transfer of airborne particles.

The effect of ventilation on airborne contamination was studied in a new operating suite containing operating rooms with conventional ventilation (17-20 turnovers/h) and operating rooms with zonal ventilation, where the turnover in the central part of the room was approximately 80/h. The efficacy of the ventilation was first examined with gas tracer experiments and found satisfactory. Experiments using potassium iodide particles showed the transfer between adjacent rooms in the suite to be less than 10(-3)% with closed doors and from 1% to 2.5 x 10(-2)% when the doors were opened once a minute. The transfer between two adjacent operating rooms was calculated to be approximately 10(-4)%. There is thus little risk of spread of airborne infection between operating rooms.Experiments with potassium iodide particles showed that in operating rooms with zonal ventilation the particle concentration in the centre of the room was about one-tenth that in the periphery; in conventionally ventilated operating rooms the concentration was about one-half. With bacteria-carrying particles generated by human activity the concentration in the centre of operating rooms with zonal ventilation was about half that in the periphery both during experimental activity and operations; in conventionally ventilated operating rooms it was about equal in both cases. Bacterial counts at the periphery were found to be lower in rooms with zonal ventilation ( approximately 50 c.f.u./m(3)) than in conventionally ventilated ( approximately 70 c.f.u./m(3)).


Bacterial contamination control mats: a comparative study.

The ability of six different types of contamination control mats currently in use at the entrances to theatre suites and other clean areas to remove bacteria-carrying particles from theatre trolley wheeels was compared. Marked differences in the effectiveness of this property were obtained; and all mats showed some disadvantages. Modification of one of the mats has resulted in improved efficiency under working conditions.


Air exchange through doorways. The effect of temperature difference, turbulence and ventilation flow.

Analytical expressions have been derived for the exchange of air across doorways or similar apertures, in terms of the temperature difference between the spaces on both sides of the opening and the net volume of air flowing through this as a result of unbalanced air supply or extract. A simple allowance for turbulence which gives reasonable correspondence with observation is included. The formulae, which assume complete air mixing on both sides of the doorway up to the plane of the aperture, predict outflows from the warmer side, when there is an excess air supply to this side, which are progressively smaller than those observed as the temperature difference rises above 2-3 degrees C and the volume of excess air supply increases to produce an averaged outflow velocity greater than 0-1-0-15 m/s. This seems to be due to lack of mixing of the warm outflowing air with the cooler air mass. A correction factor for this can be deduced as a function of the pressure difference due to the excess air supply. The limiting magnitude and general form of this function are compatible with a simple theoretical model of the air flow patterns involved.


Age-sex incidence in symptomatic allergies: an excess of females in the child-bearing years.

Eight-hundred and one patients amongst 1912 referred for skin testing because of suspected allergies were found suffering from asthma due to the house-dust mite or from grass pollenosis. They were analysed in terms of sex, age of referral and age of onset of symptoms. Amongst children referred below the age of 10 with house-dust mite asthma the ratio of males to females was 3:1; with grass pollenosis 2-1:1, as expected. The sex ratio gradually became reversed with increasing age of referral, females overtaking males in the third decade. Female-male ratios increased to a mean of 1-8:1 in the fourth and fifth decades. Reliable ages of onset of symptoms were obtained in 388 males and 323 females. Of these, 280 males and 162 females experienced their first symptoms before the age of 10 whereas 96 males and 148 females first developed symptoms between 10 and 29 years of age. The remaining 12 males and 13 females showed their first symptoms after the age of 29.


Virulence factors of Francisella tularensis.

The mechanism causing viable Francisella tularensis to lose virulence in aerosols has been investigated. Fully virulent organisms were found to be encapsulated and avirulent organisms from aged aerosols, decapsulated. Capsules were also removed by suspension of F. tularensis in hypertonic sodium chloride. The resulting naked, but viable, organisms were predominantly avirulent for guinea-pigs challenged intraperitoneally. Capsular material and cell walls were found to contain large amounts of lipid, about 50 and 70% (w/w) respectively, and to differ in lipid and sugar composition. Isolated capsular material was not found to contain a lethal toxin for mice or guinea-pigs, or to induce an immunological response in these animals to fully virulent F. tularensis.


Salmonella serotypes, Salmonella typhi phage types, and anti-microbial resistance at the University Hospital of the West Indies, Jamaica.

Bacteriologically proved cases of salmonellosis presenting at the University Hospital have increased nearly threefold since 1957. The most striking change has been a considerable increase in the incidence of Salmonella heidelberg and Salmonella derby in the last 5 years, probably resulting from hospital acquired infection. About 80 cases of typhoid fever are reported each year in Jamaica. There has been little change in the prevalence of different phage types of Salmonella typhi since 1961. Paratyphoid fever is rare. Standardized antimicrobial disk-sensitivity testing was performed on selected surviving salmonella strains since 1964. S. typhi has remained fully sensitive to all the agents tested except streptomycin. Other salmonellas, however have shown a significant increase in antimicrobial resistance since 1970. Most of this increase was due to multiple resistance in S. heidelberg and S. derby, and the survival and dissemination of these strains in the hospital environment may be related to antibiotic usage.


Travellers' diarrhoea: does it occur in the United Kingdom?

Of 485 persons who replied to a questionnaire after attending a European Congress in September 1974, diarrhoea was experienced by 4 of 143 British residents and 2 of 342 visitors to the United Kingdom. This extremely low incidence of travellers' diarrhoea contrasts with the high incidence reported in travellers from countries with cool climates and north European standards of hygiene to countries where these conditions do not hold.


The laboratory surveillance of influenza epidemics in the United Kingdom 1968-1976.

The extensive laboratory investigations of respiratory disease in the U.K. over many years have demonstrated the frequency with which influenza viruses, both A and B, are found each winter. Only rarely are none isolated. These findings correlate well with other indicators of influenza such as increases in sickness benefit claims and in deaths attributed to influenza and pneumonia. However, outside these demonstrable peaks of incidence influenza viruses have been found to circulate over considerably longer periods often first appearing as early as November and continuing through to April or even May. But there has been no regular or predictable pattern determined. The period of 1968-76 has seen a series of differently developing influenza winter epidemics caused by a series of the H3N2 virus. The contributions of virus isolation and serology to influenza surveillance is discussed.


The cellular transport of chloramphenicol and thiamphenicol.

The transport of chloramphenicol (CAP) and thiamphenicol (TAP) was examined in several mammalian cell systems. Chloramphenicol was concentrated by all cells by a factor of 2 to 4 (cellular/extracellular concentration [CE] ratio). Both the uptake and efflux were rapid and temperature independent. In contrast, the influx and efflux of TAP progressed slowly at 37 degrees C over a period exceeding 30 min, the maximal C/E ratios in most instances being slightly greater than 1. Thiamphenicol was virtually excluded from cells at 0 degrees C. Cells preloaded with TAP at 37 degrees C lost little or no drug at 0 degrees C. The uptake of labeled CAP and TAP was uninfluenced by metabolic inhibitors, and was only slightly reduced by the presence of relatively large concentrations of unlabeled drug. This transport pattern is most consistent with a mechanism of simple diffusion based on partitioning of CAP in cellular compartments. It is postulated that the greater polarity of the methylsulfonyl moiety of TAP renders this drug less soluble in membrane lipids and hence more slowly diffusible. The possible significance of these findings in relation to hematologic toxicity from CAP is discussed.


Results of standardized lip repair after tumour resection.

Modifying and extending Bernard's method Fries (1971) developed a universal technique for reconstructive surgery of the lip after tumour resection. So far this technique has been employed in 80 cases, 50 of which were available for follow-up studies. Cosmetic results were invariably found to be optimal. Functional deficits were predominantly associated with whistling and pouting, while eating, speaking and laughing were unimpaired.


Kaposi sarcoma on the base of the tongue. Case report.

A 76-years-old female (housewife) with a Kaposi sarcoma presenting as a single, isolated pedunculated tumour on the base of the tongue, is described. No skin or alimentary tract involvements were found, and  there were no signs of recurrence locally or generally with the exception of one nodule on the neck 3 years after a local removal.


Multiple recurrent central giant cell granulomas of the jaws. Case report.

A case of a 31-year-old Caucasian female with multiple recurrent central giant cell granulomas of the maxilla and mandible is presented. The patient's mother was also treated for an extensive giant cell granuloma of the maxilla. Hyperparathyroidism was excluded.


Sail flap excision for the iguana neck deformity.

A method of recontouring the lax submental tissues of the sagging neck is discussed.


Reduction cheiloplasty: its role in the correction of dentofacial deformities.

The presence of prominent lips is common in individuals with various dentofacial and craniofacial deformities. The aetiology must be diagnosed to differentiate between pseudo-macrochelia and true macrocheilia. When considering surgical correction of the prominent lip, a precise description of the location and the magnitude of the deformity is required. With careful treatment planning, proper sequencing of the treatment, and a good understanding of the various surgical techniques, optimum results can be achieved. These aspects will be discussed in detail illustrated with appropriate cases.


Sagittal splitting of the body of the mandible (Mehnert's technique) for correction of open bite and deep over bite.

The sliding of the inner and outer cortex of the mandible based on the sagittal splitting (Obsegeser 1955) is usually confined to the ramus and angle area. It can, however, also be performed in the body of the mandible even in cases with normal dentition. In these cases, the sagittal split is carried out below the dentoalveolar region (Mehnert 1959). The technical possibilities and the experiences made are shown. It can be concluded that this technique is particularly indicated in cases of open bite and severe deep over bite whether they are associated or not with a prognathism or retromandibulism of moderate degree.


Surgical treatment of habitual luxation of the temporomandibular joint.

The various operations which aim at increasing the articular eminence are discussed. A modifications of one of these procedures is described in detail with reference to 12 patients on whom this operation was performed 23 times. In discussion of advantages and disadvantages, the results obtained are compared with those of a procedure which produces the opposite effect, namely a flattening of the articular eminence of the temporomandibular joint. It is finally demonstrated that the two procedures can effectively complement each other, provided they are carried out for the correct indication and in the proper sequence.


Malar bone fractures: experimental fractures on the dried skull and clinical sensory disturbances.

To improve understanding of malar bone fracture, experimental fractures on dried skulls and clinical sensory dysfunctions were investigated. In the experimental study, the fracture lines are largely confined to the suture lines between the zygoma and neighbouring bones in addition to the maxillo-ethmoidal suture. Antral walls, anterior and posterior, are relatively free from fracture lines in the region of the superior dental plexus. This coincides with the findings of dento-alveolar sensory disturbances which are relatively lower in incidence and earlier in recovery than those following Le Fort type fractures. To study this sensory status gives interesting information about the fracture lines and the anatomical course of the superior dental nerves.


Principles of the surgical therapy of eyelid tumours.

The case histories of 290 eyelid tumours at the North-West Germany Clinic for Maxillo-Facial Surgery, Hamburg, are evaluated and the experiences gained in the surgical therapy of this type of tumour reported. It is emphasized how necessary it is that the radicality of tumour resection by controlled by frozen section microscopy during the operation. This ensures a low recurrence rate. The results which were evaluated at the earliest six months after eyelid reconstruction, show that, despite different initial situations, a high percentage of both good functional and aesthetic results may be obtained after extensive tumour resection. This requires that the reconstructive method most suitable for the individual case be chosen out of the wealth of techniques. The most important ones used at our hospital are discussed on the basis of various examples.


Chemotactic defect in Wegener's granulomatosis.

Chemotaxis of the polymorphonuclear (PMN) leukocytes from nine Wegener's granulomatosis patients was examined in vitro. All the patients except one showed remarkable decrease in their chemotactic activity: This might be caused by abnormality in the PMN leukocytes themselves. It was confirmed that there was no increase in chemotactic inhibitory substance(s). There was chemotactic factor(s) in sufficient amount in the serum to react with the antigen-antibody complex for normal chemotaxis. As to the random mobility of PMN leukocytes there was no abnormality in these patients.


Iodoamino acids in abnormal and grossly normal thyroids: Comparison between 125I and 127I distribution.

Patients with thyroid cyst (TC), non-toxic nodular goiter (NNG), follicular adenoma (FA) and papillary carcinoma (PC) were given a tracer dose of 125I 40h prior to surgery. Tissue specimens were hydrolysed with Pronase and their labeled iodocompound distribution determined by paper or thin layer chromatography; they were then derivatized and their stable iodoamino acids (IAA) determined by gas liquid chromatography (GLC). Specific activity (SA) of MIT, DIT and T4 was within the same range in TC, FA and grossly normal part of a PC, and was markedly lower in two NNG. SA of T3 was very high in a TC, and higher than that of other IAA, in one NNG, indicating preferential synthesis. SA of MIT and DIT was very high in grossly normal part of a second PC but stable iodothyronines were undetectable. Specimen therefore was biochemically abnormal though grossly normal. In the two abnormal specimens of PC stable IAA were undetectable, even though type of distribution of labeled IAA in one specimen closely approximated that found in TC, FA and NNG. In a second abnormal PC specimen RAI uptake was too low for analysis to be carried out. By combining labeled and stable IAA measurements new parameters for studying human thyroids have been obtained.


Studies on the topical action of 10-undecen-1-il thiopseudourea iodide (AHR-1911) in acute and chronic dermatitis.

As a follow-up of a preliminary trial, the therapeutic results obtained in 40 cases of acute and chronic dermatitis by the topical application of 10-undecen-1-yl-pseudothiourea hydroiodide (AHR-1911) in an evanescent vehicle containing triethanolamine stearate are presented. The treatment led to complete remission in 14/40 and to favorable results in 18/40 cases. In 2 out of 3 cases of infantile atopic dermatitis improvement was followed by relapse. The responsiveness to AHR-1911 of patients with delayed hypersensitivity, which requires steroids for treatment, is considered of clinical importance. The prompt action of the drug in acute dermatitis, such as is produced by insect-bites, appeared to be impressive. None of the total of 50 cases treated by the author with this new preparation showed any manifestation of intolerance or reaction to the drug.


Canine and human renal toxicity of inosine dialdehyde (NSC 118994).

A new antitumor agent, inosine dialdehyde, has shown minimal hematologic, but dose limiting, renal toxicity. The renal impairment is tubular necrosis due to reduction in renal blood by the drug. In addition, elevated serum calcium will return to normal within one week of drug administration. This effect is not secondary to urinary calcium excretion, but possibly an alteration of bone metabolism.


Antileukemic properties of combinations of radiation and malonato(1,2-diaminocyclohexane) platinum(ii) (NSC-224964).

Mean survival times were increased an average of 23, 53 and 61%, when 10, 15, and 20 mg/kg, respectively, of the organoplatinum congener, malonato(1,2-diaminocyclohexane) platinum(II)(NSC-224964), was given as the only treatment modality to BDF1 mice bearing 1-day-old L1210 leukemia. When a single dose of 10 mg/kg was combined with either 300 or 100 R on day 1 only, the anticipated response (ILS = 30 and 38%, respectively) based on the additive effects of the single modalities was surpassed by 26 and 21%, respectively (i.e. extent of therapeutic synergism). When divided doses of radiation (200 R/day x 3 days) were combined with 15 or 20 mg/kg of NSC-224964, survival times were enhanced an average of 15% (extent of synergism) greater than would be expected if these modalities were acting through an additive process(es).


Effects of edible oils on blood and arterial lipids in rats after one year's balanced normolipidic diet.

Male Sprague-Dawley rats were fed during one year with diets containing 12% of one of the following fats: butter, sunflower oil, rapeseed oil, soybean oil, hydrogenated soybean oil, palm oil, canbra oil and arachid oil. Total serum cholesterol was lower in the arachid, suflower and butter groups and higher in the palm and hydrogenated soybean groups (p less than 0.01); serum cholesterol esters were lower in the arachid, sunflower and soybean groups, but higher in the palm and hydrogenated soybean groups ( p less than 0.01). Serum triglycerides were lower in the sunflower and arachid groups and higher in the butter and palm groups (p less than 0.01). There was a positive, significant correlation between serum cholesterol and phospholipids in the various groups. In aortas, free cholesterol levels were the same in different groups, but cholesterol ester levels increased in the following order: canbra, butter, arachid, palm, sunflower, rapeseed, hydrogenated soybean and soybean red groups (p less than 0.01). There was a significant correlation between aorta cholesterol esters and the ratio 18:0 + 18:1 of the dietary fat (r = 0.69; p less than 0.001).


Is interferon tissue specific?- Effect of human leukocyte and fibroblast interferons on the growth of lymphoblastoid and osteosarcoma cell lines.

The growth inhibitory effect of human leukocyte and fibroblast interferons was tested in vitro. The effect of fibroblast interferon was more pronounced on osteosarcoma cells and the effect of leukocyte interferon was more pronounced on lymphoid cells. This suggests that the capacity of interferon to inhibit cell growth is, in some measure, tissue specific.


The manpower survey of oral surgery in 1974. Part 1 of two parts. 1. Introduction and some general characteristics of oral surgeons.

Questionnaires requesting much data about oral surgeons and their practice of the specialty were mailed to the members of the American Society of Oral Surgeons. A total of 2,251 usable questionnaires were returned. The methods used in the survey and to summarize the data have been described and some general characteristics of the responding oral surgeons have been supplied in this report. Almost 76% (75.8%) of the oral surgeons returned usable questionnaires. Only 2.4% of the respondents were younger than 30 years and 60.5% were in the age range of 30 to 44 years. The average age of all respondents was 43.0 years. Slightly more than 80% participate in private practice either full-time or part-time teaching. Only 5.1% of the respondents aged 65 to 69 had retired. Almost 82% (81.7%) were active members of the Society. More respondents (24.7%) practiced in cities with populations larger than 500,000 and only 4.5% practiced in cities with populations less than 25,000. More than half of the 2,251 respondents (53.8%) practiced in cities with populations less than 150,000, and 44.4% were in cities with populations less than 100,000.


Current concepts of blood transfusion.

Extensive research into the physiology of red blood cells and platelets has shown that it is more advantageous to separate blood into its components than to store it as whole blood. After the red blood cells and platelets have reached the restricted period of storage in the liquid state, they can be freeze-preserved and stored for prolonged periods. Plasma can be frozen for future use or can be fractionated into the various stable components. The use of a combination of liquid-preservation and freeze-preservation methods affords a more efficient use of the limited supply of available blood.


Hemodynamic effects of locally applied epinephrine used with various general anesthetic techniques.

Halothane-nitrous oxide-oxygen (GOF), nitrous oxide-oxygen with diallyl-nor-toxiferine (Jackson-Rees method), or nitrous oxide-oxygen with droperidol-pentazocine (modified NLA) were administered in 190 instances of repair of cleft lips and cleft palates. Epinephrine, 1:30,000, 1:100,000, or 1:300,000, was injected as the vasoconstrictor around the operative field. Epinephrine concentration of 1:100,000 provided sufficient hemostasis, whereas 1:300,000 was insufficient. With the same concentration of epinephrine, GOF and modified NLA seemed to be better than the Jackson-Rees method, since the GOF and modified NLA groups showed less increase of pulse rate, blood pressure, and plethysmographic changes. A 1:30,000 concentration of epinephrine could be used safely with the Jackson-Rees method and the hemostasis with this concentration was superior to 1:100,000. However, it is recommended only for the cleft lip operation, since these patients are younger and need better hemostasis, and hypersalivation after reversal does not disturb the postoperative course. So-called epinephrine-induced arrhythmia with halothane anesthesia occurred in 1 of 34 instances with 1:300,000 solution and in 5 of 48 instances with 1:100,000 solution. Propranolol was given in only one instance. All others returned to normal rhythm with hyperventilation with pure oxygen. The use of 1:100,000 solution of epinephrine as an adjunct with modified NLA is the most satisfactory and safe method for cleft palate operations, and 1:30,000 with the Jackson-Rees is the better method for cleft lip repairs.


Coccidioides immitis osteomyelitis of the mandible in an infant.

Coccidioidomycotic osteomyelitis developed at the angle of the right side of the mandible in a 5-month-old Papago infant. The disease was successfully treated with a combination of amphotericin B, surgery, and transfer factor with complete immunological, microbiological, and radiological cure. At 4 years of age, the only residual effect is prominence of the right hemimandible with asymmetry of the jaw.


Fatal mediastinitis after a dental infection.

The pertinent features of life-threatening complications of dental infections have been briefly reviewed with particular emphasis on the alterations of the clinical features of these conditions induced by antibiotic therapy. The clinician who deals with dental infections must exercise a high index of suspicion to consistently abort the development of these complications, especially when treating debilitated patients or individuals with compromised immune functions.


Necrotizing fasciitis.

Necrotizing fasciitis is a relatively uncommon severe soft tissue infection that is characterized by rapid widespread superficial fascial necrosis with undermining of surrounding soft tissue. Recent advances in anaerobic culture techniques have allowed identification of anaerobic organisms, which are now considered to have a vital role in the pathogenesis of this soft tissue infection. Therapy requires both rapid institution of a high level of antibiotics and a radical surgical incision and drainage procedure. All of the aerobic and anaerobic organisms isolated in the reported case of necrotizing fasciitis arising from a periapically infected mandibular third molar demonstrated in vitro sensitivity to penicillin.


Metastatic thyroid carcinoma of the mandible mimicking an arteriovenous malformation.

A case of thyroid carcinoma metastatic to the mandible is presented. Particular attention has been called to its extremely vascular nature and a recommendation has been made that all lesions of such suspected vascularity should be preoperatively studied by angiography in an effort to provide insight into the nature of the lesion as well as the exact blood supply. With this information, appropriate devascularization either by surgical ligation or intravascular embolization can be performed before biopsy and hence sudden and potentially overwhelming hemorrhage during incisional or excisional surgery can be avoided.


Pedicle tongue flap for closure of an oroantral defect after partial maxillectomy.

The position, size, and composition of the tongue make it ideal as a potential donor site for repair of certain oral defects. Adherence to principles of sound flap design must be followed. A technique for closure of large oroantral communications with use of a pedicled graft from the lateral border of the tongue has been described. This procedure provides the patient with immediate repair of the defect, while maintaining the relatively normal anatomic architecture of the oral cavity. We believe that this technique is also applicable to closure of other types of oroantral defects in addition to those described.


Immediate reconstruction of an orbital complex fracture with autogenous mandibular bone.

A case of fracture of the zygomaticomaxillary complex with an associated defect of the infraorbital rim and orbital floor is discussed. Use of the lateral plate of the mandibular ramus to reconstruct the defect and advantages of this technique are discussed.


Zygomatico-coronoid ankylosis.

Although zygomatico-coronoid ankylosis may have been encountered by many oral surgeons, its occurrence has rarely been reported. A review of the literature has disclosed only nine reported cases. The treatment of these cases has been by coronoidectomy with either an intraoral or extraoral approach.


Oral dysplasia and in situ carcinoma: clinicopathologic correlations of eight patients.

Eight patients with multiple oral dysplastic epithelial lesions were followed by clinical examinations and serial biopsies for periods varying from four to 22 years. The dysplasias and in situ carcinomas were characterized by persistence, recurrence, and eventual progression to invasive squamous cell carcinoma. It could not be determined whether dysplasia and in situ carcinoma were separate clinical-pathologic entities with similar end points or whether they were part of a continuum in a spectrum of epithelial neoplasia. The need for close clinical observation and local excision was emphasized because of the multiplicity of lesions and because of the protracted clinical course. Treatment of these patients was problematic because of similarities of the disease to lichen planus. It is possible that they had a premalignant disease process that mimicked lichen planus, or that they had an unusual form of lichen planus for which criteria have not been established. The progressive nature of the disease was exemplified by one death, one patient with cervical metastasis, and one with generalized remote metastatic disease.


Retreatment in periodontal practice.

Periodontal disease has a greater or lesser tendency to recur. The therapist controls rather than cures the condition. Careful maintenance is as important as skillful original treatment if periodontal health is to be maintained. At the time of the original treatment, every patient should be informed that retreatment of some type is occasionally necessary. Patients with recurrence of disease should be treated as conservatively as possible and every effort should be made to find the cause of failure. Surgical retreatment should be done only after a reasonable effort has been made to improve the situation by other means. The deepened crevice that does not bleed when probed and is not accompanied by bone loss does not provide justification for surgical retreatment. This report has reviewed some of the reasons for treatment failures and has presented a philosophy for their management.


Effect of chlorhexidine on the hamster cheek pouch. Microcirculation and penetration studies.

The application of chlorhexidine gluconate on the intact cheek pouch of hamsters led to an immediate increase of flow velocity determined in venules beneath the epithelium. The application of [14C]chlorhexidine on the intact cheek pouch led to accumulation of labeled material in the liver and kidneys. Both findings indicate that penetration of the drug occurred through the epithelium of the cheek pouch.


A study of the acceptability of lateral records by the Whip-Mix articulator.

1. Of 50 lateral condylar settings made, 10 were not accepted by the Whip-Mix articulator. 2. An improved method of obtaining lateral interocclusal records was described. 3. The Whip-Mix articulator is considered useful in diagnosis and treatment in prosthodontic procedures if one is aware of its limitations.


Biologic laws governing functions of muscles that move the mandible. Part II. Condylar position.

A model to quantify muscle response to occlusal contacts is useful in developing an understanding of the mechanism by which the occlusion programs muscle function. A knowledge of how the occlusion programs muscle function enables the dentist to develop manipulative skills of the mandible which are necessary for diagnosis and effective occlusal treatment. This article presents complicated neuromuscular responses (reflexes) to occlusal contacts in an oversimplified way and with analogies so that the clinical significance of these neuromuscular reflexes in diagnosis and treatment can be more easily understood.


[Acute lymphoblastic leukemia and lymphoblastic lymphoma. Two names for one disease (author's transl)].

Of 14 non-T-cell malignant non-Hodgkin lymphomas (mNHL) 5/14 presented with leukemic transformation of the bone marrow; in three more cases bone marrow involvement developed during an observation period of 60--200weeks. In 2/14 cases mNHL terminated the first continuous and complete remission of acute lymphoblastic leukemia (ALL). CNS involvement has been observed without preceding bone marrow involvement. Only 4/14 mNHL remained local diseases. These clinical courses as well as hematological findings and further clinical observations suggests a very close relationship between mNHL and ALL if not basic identity. With the same systemic treatment additional to local treatment, prognosis of mNHL is by no means worse but rather better than the prognosis of ALL.


[Reimplantation of a mandibular segment resected for the removal of a voluminous osteoma].

Total resection of the host bone for compact voluminous osteoma of the angle and ascending branch of the mandible was followed by immediate reinsertion of the unimpaired segment in its original site. Radiographical check-up 2 yrs later showed that the segment was notably atrophic and flattened, and looked like a long-standing iliac crest graft.


[Hyperostosis on the alveolar process margin].

Defects of the bone margin requiring ostectomy and osteoplasty include hyperostotic processes, formations which, while recalling palatine and mandibular tori, have their own nosological slot. Hyperostosis is characterized by thickening of the cervical margin and is linked by a narrow isthmus to the underlying bone plane; it occurs with greatest frequency in the vestibular region. The personal case, in a man of 52, presented two sausage-shaped protuberances located apically at the alveolar margin in the two left arches. Their removal presented no problem of surgical technique as the hyperostosis had no close links with the underlying bone planes. Histological examination of the fragments showed that the hyperostotic tissue consisted of fascicular bone with an intima vascular component. Two years after the operation, the patient presents no signs of relapse and would appear to be completely cured.


[The topical use of Boutycin (indomethacin) in odontostomatology. Clinical study].

The effect of indomethacin used topically for postoperative pain and oedema has been studied. The effect is positive and is particularly evident in the case of pain.


[Leukemic meningeal involvement in adults and its treatment].

The authors report two cases of acute leukaemia in adults with development of sings central nervous system involvement at the time of full haematological remission. In the first case the diagnosis was: acute undifferentiated-cell leukaemia, in the second one: acute lymphoblastic leukaemia. In both cases in the first stage of the disease complete remission of neurological manifestations was obtained; in the second case it was also obtained after the following relapse. In the first case death occurred during successive haematological exacerbation. Ametopterin was given intrathecally or X-ray therapy was applied.


Pulpal status after autogenous transplantation of fully developed maxillary canines.

By means of histologic and histochemical studies of oxidative enzymes, the pulps of transplanted fully developed maxillary canines have been evaluated after an observation period of 3 to 25 months. No pulp had survived the transplantation trauma, and endodontic treatment of fully developed transplant teeth was considered to be a prerequisite to an optimal clinical result.


Scanning microscopic evaluation of canal débridement as compared to present methods.

Ninety-one samples of root canal contents were obtained from thirty-one teeth. The paper point samples were evaluated for exudate, subjected to bacteriologic analysis, and/or examined with the scanning electron microscope. A comparison was made between the presence or absence of exudate, positive and negative cultures, and the presence or absence of contaminants as examined under the SEM. All three methods of evaluation showed some degree of correlationmscanning electron microscopy appears to be a more sensitive test for canal status.


Effect of lavage on the incidence of localized osteitis in mandibular third molar extraction sites.

Four hundred twenty-two mandibular third molars were extracted in 211 patients. After extraction, one half of the surgical sites were subjected to a 175 ml. lavage with normal saline solution, and the other half received a lavage of less than 25 ml. of normal saline solution. Comparisons revealed the following: 1. The overall incidence of localized osteitis was 8.3 per cent (thirty-five of 422 sites). 2. Localized osteitis occurred at twelve of 211 (5.7 per cent) sites which were subjected to the higher-volume lavage. 3. Localized osteitis occurred at twenty-three of 211 (10.9 per cent) sites which were subjected to minimal lavage. 4. The incidence of localized osteitis was determined in the various age groups as follows: ages 15 to 20, 5.0 per cent; ages 21 to 35, 10.4 per cent; ages 26 to 30, 14.7 per cent. 5. Localized osteitis occurred at eight of 175 (4.5 per cent) partial-impaction sites, whereas it occurred at twenty-seven of 246 (11 per cent) complete-impaction sites. 6. The incidence of localized osteitis at extraction sites in female patients taking oral contraceptives was 19.4 per cent (seven of thirty-six sites). 7. Postoperative infection occurred at seven of 422 extraction sites (1.4 per cent); six of these occurred at sites which were subjected to minimal lavage. These results indicate that the use of a 175 ml. lavage with normal saline solution after extraction of mandibular third molars will significantly reduce the incidence of localized osteitis to approximately one half of that observed when only a minimal-volume lavage is used. The results also suggest that age, type of impaction, and whether the patient is taking oral contraceptives are all important factors to be considered in the incidence of localized osteitis.


Xeroradiography of dental structures. I. Preliminary investigations.

Xeroradiography has several inherent technical advantages over intraoral film radiography, as well as many convenience features. We found that a conventional dental x-ray unit can act as an excellent source of radiation for xeroradiography of dental structures. Furthermore, high-quality images of soft tissue, bone, and teeth were produced at radiation exposures up to seven times less than for conventional intraoral film radiography. This demonstration of reduced radiation exposure should further encourage research into the applicability of xeroradiography to the imaging of dental structures.


Oral manifestations of an arteriovenous anastomosis.

Described is the case of a healthy 30-year-old Caucasian man who presented with marked unilateral loss of alveolar bone and tooth mobility on the left side. The history and clinical signs and symptoms were consistent with the diagnosis of congenital arteriovenous anastomosis.


A modified stent for decompression of cysts.

Presented is a simple method for decompression of a cyst with the use of a modified stent. The patient is instructed in methods of removal, insertion, and irrigation by means of a blunt No. 16 gauge needle. Periodic follow-up radiographic examinations permit reduction in tube length as the defect "fills in".


Ameloblastoma of the maxilla. Report of a case.

Reported is the case of a well-circumscribed radiopaque ameloblastoma of the maxilla. Treatment was by means of a conservative partial resection of the maxilla. The procedure was successful in completely removing the tumor mass without causing any noticeable facial disfigurement. Long-term follow-up was stressed to the patient for early detection of any recurrence.


Tetracycline-induced extrinsic discoloration of the dentition.

Tetracycline, a broad-spectrum antibiotic, is known to cause intrinsic discoloration of the dentition. A case is being presented of extrinsic discoloration of the teeth associated with the use of this drug. This is believed to be the first such reported case in the literature. Possible mechanisms of how tetracycline may cause extrinsic tooth discoloration are discussed.


Clinicopathologic effects of cancer chemotherapeutic agents on human buccal mucosa.

Specimens of buccal mucosa obtained at autopsy from 216 patients were examined for histopathologic alterations. Atrophic oral epithelium was found in thirty cases. A retrospective study of the hospital records revealed that thirteen of these latter patients had been on a cancer chemotherapeutic regimen prior to death. There was a significantly higher incidence of atrophy in the chemotherapy group (p less than 0.001) than in control patients. These findings, as well as the expected inherent susceptibility of rapidly replicating oral epithelial cells to metabolic inhibitors, suggest a causal relationship between oral atrophy and the administration of cancer chemotherapeutic agents. This atrophy may therefore represent a preliminary stage of mucosal alteration that ultimately progresses to the clinical sequelae of stomatitis and oral ulcerations frequently encountered during cancer chemotherapy. Some alternative mechanisms are also discussed.


Why can't you achieve adequate regional anesthesia in the presence of infection?

Observed in this study were morphologic changes in inflamed nerves, along with biochemical changes, which appear to act concurrently to deactivate or prevent activation of the local anesthetic solution. Morphologic changes were observed along the nerve fiber distant from the inflammatory site. These neuro-degenerative changes were seen at the axon and myelin sheaths level. The biochemical data support the presence in the inflamed nerve of amino acids which may be the product of lysosomal rupture and proteolytic enzyme release. These inflammatory mediators may affect either the local anesthetic or the environment of the nerve fiber. The precise mechanism of action of these catalytic products cannot be determined from this study.


Aberrant salivary gland tissue in the anterior mandible.

Salivary gland tissue inclusions in the posterior part of the mandible are not rare. Inclusions in the anterior portion, however, are very unusual, and the case presented here brings the number of reported cases up to a total of seven. The aberrant gland appeared on a panoramic radiograph as a radiolucency judged to be a periapical lesion on the right mandibular second premolar.


Primary localized amyloidosis of the palate.

A case of amyloid tumor of the palate is reported in a 10-year-old girl. The past history, the detailed general clinical and laboratory examinations, and biopsy specimens collected from the rectal mucosa, gingiva, tongue, and skin excluded other forms of localizations of amyloidosis. The isolated amyloid tumor is an exceptional form of amyloidosis, and in the available literature we have not found mention of its localization on the palate.


Median mandibular cyst.

Since the median mandibular cyst is an extremely rare lesion, there is difficulty in determining the nature and origin of this entity. An additional case of a median mandibular cyst is described and an attempt is made to clarify the confusion associated with the diagnosis of this lesion. After a review of the literature it is suggested that the median mandibular cyst is a much rarer entity than was previously believed.


Ewing's sarcoma of the mandible.

Ewing's sarcoma of the head and neck, particularly of the mandible, has a low incidence of occurrence (fifty-five cases in the literature). The present case report demonstrates well the clinical, diagnostic, and therapeutic features in a patient treated at the Head and Neck Service of the Fundação Antonio Prudente, São Paulo, Brazil. The etiologic, clinical, histopathologic, and radiologic features are discussed, with the conclusion that radiation is the best therapeutic procedure when associated with chemotherapy.


Microscopic study of the pulps of human teeth following vital root resection.

The effects of vital root resection upon the remaining pulp were studied in twenty-six periodontally involved human molars. The pulp was extirpated 14 days after the intervention. Granulomatous tissue present in the pulp chamber protruded from the site of the exposure as a polyp in eleven cases. Mild chronic inflammatory changes were present in the coronalmost part of the radicular pulp. The apical pulp was not affected at this time interval.


A rare presentation of splenic rupture.

Traumatic rupture of the spleen is a well known problem, complicating many types of abdominal injury. In contrast, a spontaneous rupture is a rare occurrence, mainly associated with a large spleen resulting from infections, the most common in this country being infectious mononucleosis. It is also a rare complication of leukaemias and lymphomas and the case presented here demonstrates a peculiar diagnostic problem.


[The loss of volume in modern respirators during change of compliance and resistance (author's transl)].

Respirators with constant volume proved to have a distinct loss of originally set tidal volume, when mechanical respiratory disturbances are present. In cases with decreased compliance the loss of volume is mainly caused by compression of the basic volume of the apparatus. In cases with increased bronchial flow resistance - unfavourable inspiration - expiration ratio, too short or even lacking endinspiratory pressure plateau result in the distinct decrease of the set respiratory minute volume, which then requires an appropriate correction. The degree of volume loss was measured and analysed in 10 respirators which are in current use.


[The laerdal ventilation bag for newborns and infants (author's transl)].

The Laerdal resuscitator for neonates and infants is a ventilation bag designed for resuscitation, anaesthesia and intensive care (CPAP PEEP). As the apparatus allows CPAP therapy and PEEP ventilation is particularly useful in the labour and neonate ward and in paediatric intensive care units.


5-Methoxytryptamine-induced head twitches in rats.

In rats pretreated with pargyline ip injection of 5-methoxytryptamine (5-MT), but not of 5-HT, produced characteristic head twitches. 5-HT receptor blocking agents (cyproheptadine, methergoline, mianserine, WA-335-BS, and methsergide) reduced the effect of 5-MT. These substances in doses 20-160 times higher than their ED50 in head twitch test did not antagonize the pinna reflex. 5-MT-induced head twitches were also inhibited by imipramine, morphine, phenoxybenzamine and aceperone. However, their ED50 were only 3-8 times below the doses necessary to inhibit the pinna reflex. Reserpine, phentolamine, spiroperidol, pimozide and LiCl did not modify head twitches produced by 5-MT, while PCPA even potentiated them. Our results suggest the 5-MT-induced head twitches are due to the activation of the central 5-HT mechanisms probably as a result of direct stimulation of 5-HT receptors by 5-MT. Antagonism of 5-MT-induced head twitches and the dissociation of doses effective in this test from those inhibiting the pinna reflex may be of value in the prediction of central 5-HT receptor blocking properties.


New methylcyclopentanoid terpenes from the larval defensive secretion of a chrysomelid beetle (Plagiodera versicolora).

The defensive secretion of larvae of the chrysomelid beetle Plagiodera versicolora contains two unstable, volatile methylcyclopentanoid terpenes: a dialdehyde (chrysomelidial) isomeric with dolichodial and anisomorphal, and a closely related enol lactone (plagiolactone). Chrysomelidial and plagiolactone are shown to have structures III and IV on the basis of a detailed analysis of their spectra, coupled with chemical transformations to products of known structure.


Conformational basis for the activation of adenylate cyclase by adenosine.

The ability of adenosine to stimulate adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] and increase adenosine 3':5'-cyclic monophosphate (cAMP) levels has important biochemical consequences. These include the suppression of immune responses and cardiovascular effects. Recent investigations involving the ability of adenosine and adenosine analogs to stimulate adenylate cyclase provided experimental data that appear to be correlated with the ability of adenosine and analogs of adenosine to exist in the glycosidic high anti conformation. 9-beta-D-Arabinofuranosyladenine, which is not stable in the high anti conformation, is inactive as a stimulator of adenylate cyclase. 2'-Deoxyadenosine is also not stable in the high anti conformation but its instability may be significantly decreased by intramolecular adjustments promoted by receptor or active site interactions. 2'-Deoxyadenosine does not activate adenylate cyclase in lymphocytes when ATP is the substrate but is able to activate adenylate cyclase when 2-fluoro ATP is the substrate. The inability of certain analogs of adenosine, with bulky groups substituted for hydrogen at the 8 position of the adenine base, to activate adenylate cyclase and increase either lymphocyte or cardiac cell cAMP levels is consistent with the designation of the high anti conformation as being the conformation required for the activation of adenylate cyclase. An understanding of the glycosidic conformation required by the extracellular adenosine receptor of the adenosine molecule provides the basis for designing nucleoside analogs of adenosine that will exert a desired effect on cAMP levels. The avoidance of unwanted immunosuppressive or cardiotoxic effects can be arranged by structural changes that prohibit the high anti conformation.


Synthesis of 13,14-dehydroprostacyclin methyl ester: a potent inhibitor of platelet aggregation.

The structure of the most recently discovered, biologically highly active prostaglandin, PGI2 or prostacyclin, is correctly predicted on biogenetic grounds, and a general synthesis starting with prostaglandins of the F2alpha series is reported. Starting with the biologically active 13,14-dehydro-PGF2alpha, the synthesis involves formation of a 5-bromo-6,9alpha-epoxy derivative, followed by esterification and dehydrobromination of the methyl ester to form the prostacyclin structure. The stereochemistry at C-5 and C-6 of all reported products is assigned on the basis of experimental findings and mechanistic reasoning. 13,14-Dehydroprostacyclin methyl ester is considerably more stable at pH 7.5 than prostacyclin. It inhibits platelet aggregation induced by a variety of agents and causes an increase in renal blood flow in the dog at nanomolar levels.


Oligouridylate stretches in heterogeneous nuclear RNA.

Three classes of heterogeneous nuclear RNA (HnRNA) alpha, beta, and gamma, with different chemical and physical properties, can be identified in the early sea urchin embryo by hybridization with poly(U). The relative amounts of these classes vary as a function of embryonic development. It is demonstrated here that the adenyl-containing classes of HnRNA, alpha and beta, can be subfractionated by hybridization with poly(A)-agarose into species containing and lacking oligo(U)-enriched segments. These oligo(U) segments could not be detected in gamma HnRNA, which was previously shown to also lack adenylate segments. The relative proportions of these species undergo marked changes during development from early blastula (7 hr) to mesenchyme blastula (20 hr). I propose models to explain the possible effects of complementary sequences of adenylate and uridylate on the secondary structure of HnRNA, and speculate on the functional significance of such complexes.


Cytoplasmic nonpolysomal ribonucleoprotein particles in sea urchin embryos and their relationship to protein synthesis.

We have examined the relationship between the newly synthesized mRNA that enters polysomes in sea urchin embryos and the messengerlike RNA that enters the pool of ribosome-free ribonucleoprotein particles (free RNPs or informosomes). Although the RNA in the free RNPs turns over 25% more rapidly than in the polysomes, labeling kinetics indicate that the RNA containing poly(A) [poly(A)(+)RNA] and the RNA not containing poly(A) [poly(A)(-)RNA] within each cytoplasmic compartment have very similar half-lives. The poly(A)(+)RNA from both free RNPs and polysomes binds ribosomes almost equally well in a reticulocyte lysate, and this binding is sensitive to inhibitors of initiation. The poly(A)(-)RNA from polysomes initiates as well as poly(A)(+)RNA; however, poly(A)(-)RNA from free RNPs is only half as efficient in binding to ribosomes, and by this criterion is only 50% mRNA. We have also examined the size and dynamics of shortening of the poly(A) tails of poly(A)(+)RNA from free RNPs and polysomes. Pulse-labeled poly(A) from both free RNPs and polysomes is about 180 nucleotides in length. Poly(A) shortening is very rapid in polysomes; steady-state labeled polysomal RNA is largely devoid of the 180-nucleotide-long poly(A) segments. Poly(A) shortening in free RNPs is slower; half of the poly(A) derived from steady-state free RNPs is still 180 nucleotides long. Despite this difference in the rates of poly(A) shortening, polysomes and free RNPs have very similar half-lives. There is, then, no obvious relationship between poly(A) shortening and turnover of mRNA in these embryos. The data are interpreted to mean that poly(A)(+)RNA from free RNPs is enriched for a class of mRNA that initiates less frequently in vivo than the bulk of the cellular mRNA.


Amino acid sequence of human platelet factor 4.

Human platelet factor 4, a protein that binds heparin, has been purified to apparent homogeneity and the complete amino acid sequence of the protein has been determined. The 70-residue polypeptide chain contains no methionine, tryptophan, or phenylalanine, and contains only a single tyrosyl residue. The sequence analysis demonstrates a highly negatively charged amino-terminal region. The carboxyl-terminal region of the polypeptide is unusual in that it contains a repetitive clustering of positively charged and hydrophobic pairs of amino acids; preliminary evidence suggests that this domain may play a role in the binding of heparin.


Synthesis of opiate peptides by a clonal pituitary tumor cell line.

Clonal mouse pituitary tumor cells, AtT-20, synthesize at least four species of peptides with opiate activity. The endorphin concentration of AtT-20 cells was estimated to be 300-600 pmol/mg of protein. The two most abundant endorphins with apparent molecular weights of 1800 and 2400 were purified 300- and 24-fold, respectively; additional minor components were found with apparent molecular weights of greater than 3000 and less than 750.


Translation of tobacco necrosis virus and its satellite in a cell-free wheat germ system.

Tobacco necrosis virus (TNV) and its satellite virus (STNV) each contain a single-stranded RNA genome, of about 1.4 X 10(6) and 0.4 X 10(6) daltons, respectively, which is very active in stimulating amino acid incorporation in a wheat germ cell-free system. With STNV RNA the predominant incorporation product of 22,000 daltons coelectrophoreses with viral coat protein and crossreacts with antibody to viral coat protein. A similar result is obtained with TNV RNA, the only major translation product being a 30,000-dalton protein which corresponds to the coat protein by gel sizing, serological tests, and tryptic peptide analysis. Other products appearing in smaller amounts are about 63,000, 43,000, and 26,000 daltons and smaller. The possible nature of these products is discussed, as well as the unusual feature of a large, presumably multigenic, viral RNA yielding the coat protein as the predominant translation product in a eukaryotic system. Much less STNV RNA than TNV RNA produces maximal translation. Cotranslation of both RNAs in vitro indicates that STNV RNA has a translational advantage over TNV RNA. The fact that these RNAs lack 5'-terminal capping and 3'-terminal poly(A) is discussed.


Studies on nucleic acid reassociation kinetics: retarded rate of hybridization of RNA with excess DNA.

The rate of reaction of excess double-stranded bacteriophage phiX174 and plasmid RSF2124 DNA drivers with enzymatically synthesized asymmetric RNA tracers was measured. Other reactions were carried out with excess Escherichia coli DNA and E. coli RNA labeled in vivo. RNA and DNA fragment lengths were held approximately equal. For each case it was shown that in DNA excess the rate constant for RNA-DNA hybridization is 3- to 4.5-fold lower than that of the renaturation rate constant for the driver DNA. This retardation was also observed in pseudo-first-order hybridization reactions driven by excess strand-separated RSF2124 DNA. It was concluded that the rate constant for RNA-DNA by hybridization depends partially on which species is in excess.


Unwinding protein specific for mRNA translation fractionated together with rabbit reticulocyte initiation factor 3 complex.

Experiments with a rabbit reticulocyte cell-free system dependent on the addition of initiation factor 3 (eIF-3) and mRNA were carried out. In this system, using ribosomal subunits, AUG(U)(n) can direct polyphenylalanine synthesis in the absence of eIF-3 at 3 mM MgCl(2). Globin mRNA was not translated under similar conditions; its translation requires the addition of eIF-3. Moreover, the maximal rate of globin synthesis was achieved when the molar ratio of eIF-3 to ribosomes was approximately 1. This was taken to indicate that some ribosomal proteins were fractionated with eIF-3 and functioned in reconstitution of salt-washed ribosomes. In our system, almost all ribosomes were active, as evident from the fact that all were found in polysomes when analyzed at the time of linear incorporation, and the molar ratio of ribosomes to mRNA was maintained at 4:1. When AUG(U)(n) was hybridized with poly(A), it could not direct polyphenylalanine synthesis with or without eIF-3 and was a potent inhibitor of the translation of globin mRNA in the presence of eIF-3. When poly(A) containing 10% U was hybridized with AUG(U)(n) and added to the cell-free system, addition of eIF-3 promoted polyphenylalanine synthesis to about 80% of control. Moreover, eIF-3 was seen to shift significantly the melting temperature of globin and synthetic double-stranded RNA. These observations suggest that extraction of ribosomes with 0.5 M KCl may release a ribosomal protein that fractionates with eIF-3. This protein may function in unwinding or melting the secondary structure of mRNA and thus facilitate translation.


Nerve growth factor in mouse serum and saliva: role of the submandibular gland.

The concept that the salivary gland of the mouse is an endocrine organ for nerve growth factor (NGF) has been reexamined. Serum concentrations of the protein have been measured by radioimmunoassay in male and female mice and in mice from which the submandibular glands were removed. In spite of the fact that the submandibular glands of male mice contained more NGF than did those of female mice, no sex differences in circulating concentrations of the factor were detected. Furthermore, serum concentrations of NGF did not change after submandibular gland removal or after administration of several autonomic agonists. These results indicate that the submandibular glands are not endocrine organs with respect to NGF. On the other hand, extremely high concentrations of the factor are normally secreted in mouse saliva at levels that reflect the sex differences in the amount of NGF present in the glands. This finding suggests that the salivary gland is an exocrine organ for NGF and that the protein may play a biological role in saliva.


4,4'-Bis (1-anilinonaphthalene 8-sulfonate) (bis-ANS): a new probe of the active site of myosin.

The interaction of myosin subfragment-1 (S-1) with 4,4'-bis(1-anilinonaphthalene 8-sulfonate) (bis-ANS) has been studied by monitoring the fluorescence of the latter when the two components form a complex. Because ATP and ATP analogs partially displace complexed bis-ANS it has also been possible to study interactions of S-1 and nucleotides by using the displacement effect. Approximate values of the parameters of these various interactions have been measured. Some possible applications of bis-ANS have been explored. For example, it provides a very convenient method for obtaining the Michaelis constant, Km, in steady-state S-1 nucleoside triphosphatase; this particular application has also provided some evidence for inferring that in Ca2+ (but not in Mg2+) adenosinetriphosphatase (ATP phosphohydrolase, EC 3.6.1.3) S-1 behaves like a mixture of two components, each with its own Km. Clear energy transfer occurs between tryptophan residues and bound bis-ANS. The fluorescence also suggests that S-1 undergoes some slow relaxations following substrate binding.


Effect of uridine on cellular UTP and glycogen synthesis in skeletal muscle: stimulation of UTP formation by insulin.

The relation between cellular uracil nucleotides and ability to synthesize glycogen was studied in rat diaphragm incubated in vitro. In the absence of exogenous uridine the tissue content of UTP and rate of glycogen synthesis decreased with time. Uridine added to the medium increased cellular UTP and UDPG and stimulated glycogen synthesis. Insulin significantly increased the synthesis of UTP from extracellular uridine. This action of insulin appeared to be due to a stimulation of phosphorylation of the nucleoside and not to an effect on transport at the concentrations of uridine studied. However, an effect of insulin on transport of uridine at low concentrations cannot be excluded.


Pregrowth hormone messenger RNA: glucocorticoid induction and identification in rat pituitary cells.

We have investigated whether the large (5- to 15-fold) stimulation of synthesis of growth hormone (somatotropin) observed upon exposure of a strain of rat pituitary (GH3) cells to dexamethasone (a synthetic glucocorticoid) arises from a stimulation of pregrowth hormone mRNA. A good agreement was observed between the stimulation of growth hormone synthesis and the stimulation of cytoplasmic levels of pregrowth hormone mRNA, assayed by translation in wheat germ extracts. Electrophoresis on formamide-acrylamide gels of oligo(dT)-treated membrane fraction RNA revealed a band that was induced by dexamethasone to about the same extent as was translatable pregrowth hormone mRNA. Elution of the band and translation in wheat germ extracts showed directly that it contained pregrowth hormone mRNA. These results suggest that the dexamethasone induction of growth hormone synthesis in GH3 cells arises from an accumulation of pregrowth hormone mRNA in the cytoplasm of the cells. The pregrowth hormone mRNA band observed by gel electrophoresis had an estimated molecular weight of 3.6 X 10(5), suggesting the existence in this molecule of an untranslated region at least 200 nucleotides in length.


Formation of the four isomers of hen egg white lysozyme containing three negative disulfide bonds and one open disulfide bond.

Reduced partially carboxymethylated hen egg white lysozyme (mucopeptide N-acetylmuramoylhydrolase; EC 3.2.1.17) (approximately 0.8 mol of [1-(14)C]carboxymethyl groups) was air oxidized at pH 8.0 and 37 degrees in the presence of 1.5 mM 2-mercaptoethanol for 36 hr. Gel filtration of this product gave the lower (native) and higher hydrodynamic volume forms, both containing radioactivity (approximately 35 and 65%, respectively). Ion exchange chromatography of the lower hydrodynamic volume forms yielded renatured lysozyme, two major radioactive samples (LH(C) and LH(D)) eluting at the positions of monocarboxymethylated lysozyme, and two minor radioactive samples eluting at the positions of dicarboxymethylated lysozyme. Sample LH(C) (approximately 23% of the radioactivity) was essentially homogeneous with respect to electrophoretic mobility, exhibited approximately 39% of the enzymic activity of lysozyme, and contained 0.95 mol of [(14)C]carboxymethyl groups. Sample LH(D) (approximately 8% of the radioactivity) was also enzymically active and contained approximately 0.5 mol of [(14)C]carboxymethyl groups; this low value is apparently due to contamination of noncarboxymethylated species. The radioactive tryptic peptides from samples LH(C) and LH(D) were characterized. The results indicated that all eight isomers, containing three presumably native disulfide bonds and one free and one carboxymethylated sulfhydryl group, are formed on air oxidation of reduced partially carboxymethylated lysozyme. Since in each of these isomers the formation of one of the four native disulfide bonds is permanently blocked, it would follow that no one of the four disulfide bonds of native lysozyme is obligatory in the formation of the other three native disulfide bonds.


Regulation by estrogen of the vitellogenin gene.

The vitellogenin gene is inactive in the liver of male Xenopus laevis, unless exogenous estrogen is administered. We have previously shown that conventional doses of estradiol-17beta result in the appearance of new hepatic messenger RNAs, some of which are encoded for vitellogenin. We now report that much higher doses of the hormone (2 mg/frog per day for 4 days) are required to elicit maximal responses. The relative levels of membrane-bound polysomes and vitellogenin mRNA were determined as a function of time and dose of hormone. Translation of total polysomal RNA in a cell-free system derived from wheat germ was used to estimate the relative levels of vitellogenin messenger RNA. Faithful translation of this messenger RNA was indicated by two lines of evidence: labeled cell-free products were immunoprecipitated with antivitellogenin antibody, and the migration of the major labeled product in sodium dodecyl sulfate/acrylamide gels was identical to that of native vitellogenin. Our results establish conditions for maximal estrogen-induced responses in this system, and are compatible with the hypothesis that a major regulatory mechanism of steroid hormones in the control of protein synthesis is that of gene activation and regulation of messenger RNA levels.


13C nuclear magnetic resonance studies of radiation damage: radiation-induced degradation of glycine.

The stable products generated in polycrystalline glycine exposed to ionizing radiation and subsequently dissolved in water were identified by using (13)C nuclear magnetic resonance spectroscopy. The study was done on isotopically enriched samples. The results can be correlated with the results of many other studies on irradiated glycine using other methods.


Elastic model of supercoiling.

An elastic model for the supercoiling of duplex DNA is developed. The simplest assumptions regarding the elastic properties of double-helical DNA (homogeneous, isotropic, of circular cross section, and remaining straight when unstressed) will generate two orders of superhelicity when stressed. Recent experimental results [Brady, G.W., Fein, D.B. & Brumberger, H. (1976) Nature 264, 231-234] suggest that in supercoiled DNA molecules there are regions where two distinct orders of supercoiling arise, as predicted by this model.


Effect of medium composition on protein degradation and DNA synthesis in rat embryo fibroblasts.

Fibroblasts in medium deficient in serum, amino acids, phosphate, or glucose stop synthesizing DNA and increase the rate of degradation of their long-lived cellular proteins approximately 2-fold. There is no difference in the rate of degradation of short-lived proteins under these conditions. Insulin, dexamethasone, and fibroblast growth factor act synergistically to inhibit protein degradation and to stimulate thymidine incorporation to about the same extent as serum. When the medium content in serum or fibroblast growth factor is varied over a wide range, there is a close, inverse correlation between the rate of protein degradation and the extent of thymidine incorporation. When serum is added to cells that have been deprived of serum, the inhibition of protein degradation is immediate whereas the enhanced rate of protein degradation in serum-free medium is attained within 1 hr after serum removal. A 30-min exposure to serum followed by incubation in serum-free medium was as effective as continuous exposure to serum in stimulating thymidine incorporation after 8-24 hr.


Nascent prehormones are intermediates in the biosynthesis of authentic bovine pituitary growth hormone and prolactin.

Major translation products of bovine pituitary RNA in a wheat germ cell-free system were identified as larger forms (prehormones) of growth hormone and prolactin containing amino-terminal extensions of 26 or 27 and 30 amino acid residues, respectively. However, translation of bovine pituitary RNA in the wheat germ cell-free system in the presence of microsomal membranes prepared from canine pancreas or bovine pituitary yielded products that were of the same size as authentic growth hormone and prolactin; by partial amino-terminal sequence analysis they were shown to contain the correct unique amino-terminal sequence of prolactin and the two correct amino termini of authentic growth hormone; moreover, they were found to be segregated within the microsomal vesicles in that they were largely inaccessible to degradation by proteolytic enzymes. When microsomal membranes were present after rather than during translation, prehormones were neither cleaved nor segregated. These results strongly suggest that the synthesis and segregation of the authentic hormone observed in the presence of membranes proceeds via a nascent prehormone rather than a completed prehormone.


Hormone-inducible casein messenger RNA in a serum-free organ culture of whole mammary gland.

The whole second thoracic mammary gland of estradiol-17beta + progesterone primed 3- to 4-week-old BALB/c female mice was induced to pregnancy-like lobulo-alveolar morphogenesis after 6-day cultivation in a serum-free culture medium containing a "growth promoting" hormone mixture, insulin + prolactin + growth hormone (somatotropin) + estradiol + progesterone. No radioimmunologically detectable casein was present in these glands. Subsequent cultivation for another 6 days in a "lactogenic" medium with the hormones insulin + prolactin + cortisol produced abundant milk-like secretory material in the alveolar lumen. RNA of the mammary gland after estradiol + progesterone priming or cultivation in the "growth-promoting" medium failed to show a measurable amount of casein mRNA activity when assayed in a cell-free protein synthesis system derived from Ehrlich ascites ribosomes, rabbit reticulocyte factors, and tRNA. However, the glands sequentially cultivated in the "growth-promoting" and the "lactogenic" media showed a high level of casein mRNA activity in the heterologous cell-free protein synthesis system. Sodium dodecyl sulfate/polyacrylamide gel electrophoretic characteristics of the immunoprecipitable (by antibody to mouse milk casein) polypeptides directed by the mammary RNA induced in organ culture medium containing the lactogenic hormones were similar to the characteristics of the polypeptides directed by mammary polysomes of lactating mice. These results demonstrate hormonal induction of a specific mRNA in a sequential two-step culture of an entire organ in a serum-free chemically defined medium.


Heteroploid conversion of human skin cells by methylcholanthrene.

Cultured epithelial cells from human skin generally had 3- to 30-fold more hydrocarbon-metabolizing activity than fibroblasts from skin of the same donor. This activity was constant for up to 55 days in primary culture but was lost rapidly upon physical subdivision of the cultures. Treatment of primary mixed fibroblasts and epithelial cell cultures with methylcholanthrene, but not phenanthrene, led to development of actively growing fibroblastic cultures with many heteroploid cells. Unique marker chromosomes, stable over a number of cell population doublings, were identified in several of the heteroploid cell strains. Pure cultures of fibroblasts from the same donors did not undergo heteroploid conversion in response to methylcholanthrene. Spontaneously occurring heteroploidy in logarithmic phase human fibroblasts is a rare event; thus, heteroploid conversion may be a useful marker for chemical transformation of human cells. Because methylcholanthrene seems to have little transforming effect on human skin fibroblasts, human skin epithelial cells, because of their hydrocarbon-metabolizing activity, may serve to convert methylcholanthrene from a distal to an ultimate carcinogenic form.


Isolation of bindin: the protein responsible for adhesion of sperm to sea urchin eggs.

The insoluble granular material of the acrosome vesicle of sea urchin sperm has been isolated and shown to be a single 30,500 dalton protein for which the name "bindin" is proposed. The data presented are consistent with the hypothesis that bindin is the adhesive responsible for the attachment of sperm to the vitelline layer of the egg. Experimental results suggest that bindin may act by binding to carbohydrate receptors of vitelline layer glycoproteins. The speculation is made that sperm bindins may be the general mechanism by which animal sperm attach to eggs.


Gene activation in somatic nuclei after injection into amphibian oocytes.

Genes that are unexpressed in somatic cells have been activated by injecting cultured cell nuclei of the frog Xenopus laevis into oocytes of the newt Pleurodeles waltlii. The genes that were activated are normally expressed in oocytes but not in cultured cells. Conversely, genes that are normally expressed in cultured cells but not in oocytes became inactive when cultured cell nuclei were injected into oocytes. These changes in gene activity were detected by two-dimensional gel electrophoresis of proteins synthesized by oocytes injected with nuclei. Controls, which included the use of alpha-amanitin, showed that these changes in protein synthesis are dependent on gene transcription. We conclude that genes that become inactive during cell differentiation can be reactivated, in the absence of cell division, by normal components of oocyte cytoplasm.


Globin RNA synthesis in vitro by isolated erythroleukemic cell nuclei: direct evidence for increased transcription during erythroid differentiation.

Murine erythroleukemic cells accumulate cytoplasmic globin mRNA during differentiation induced in tissue culture by dimethyl sulfoxide. Cellular accumulation of globin RNA may reflect transcriptional activation of the globin genes and/or posttranscriptional stabilization of globin RNA during differentiation. To evaluate possible transcriptional controls directly; globin RNA synthesis by isolated erythroleukemic cell nuclei was studied. Conditions were established for optimal nuclear RNA synthesis in vitro in the presence of a mercurinucleotide (Hg-CTP). Mercurated RNA synthesized in vitro was purified free of endogenous RNA by affinity chromatography on sulfhydryl-Sepharose, and analyzed for the presence of newly synthesized globin RNA sequences by molecular hybridization to globin complementary [32P]DNA. The results demonstrate markedly increased synthesis of globin RNA by nuclei isolated from dimethyl sulfoxide-treated cells, even within 5 min of nuclear transcription in vitro. These findings are most consistent with transcriptional activation of the globin genes upon induction of differentiation.


Binding of 25-hydroxycholesterol and cholesterol to different cytoplasmic proteins.

Studies were carried out to determine whether or not oxygenated derivatives of cholesterol (e.g., 25-hydroxycholesterol) that specifically suppress the activity of 3-hydroxy-3-methylglutaryl-CoA reductase [mevalonate:NADP(+) oxidoreductase (CoA-acylating), EC 1.1.1.34], bind to a soluble component of the cytoplasm different from that which binds the nonsuppressor, cholesterol. Density gradient fractionation of the cytosolic fraction isolated from L cell cultures that had been incubated with low concentrations of 25-hydroxy[26,27-(3)H]cholesterol or [1,2-(3)H]cholesterol provided evidence for the existence of at least two different sterol-binding proteins. Bound cholesterol sedimented in a sucrose density gradient as two or more broad bands with coefficients of approximately 9 S and 21 S. Two relatively narrow bands of bound 25-hydroxycholesterol had sedimentation coefficients of 5 S and 8 S. Preincubation of the cells with a relatively high concentration of unlabeled 25-hydroxycholesterol altered the banding pattern of the 25-hydroxy[(3)H]cholesterol taken up during a subsequent incubation period by decreasing the size of the major (8S) band. Under these conditions, cholesterol did not affect the banding pattern of 25-hydroxy[(3)H]cholesterol. The density gradient banding pattern of bound [(3)H]cholesterol was only slightly affected by preincubating the cells with unlabeled cholesterol or 25-hydroxycholesterol. Both sterols appeared to be bound to proteins because the bound sterols were eliminated from cytosol that had been heated at 100 degrees , and their sedimentation coefficients were altered by proteolysis.


Bacteriophage phiX174: gene A overlaps gene B.

The map position of several phiX174 mutations in the genes A and B was determined by marker rescue with DNA fragments produced by the restriction enzymes Hha I, HindII, Hae III, and Alu I. All the gene B mutants were found to be located within gene A. Genetic complementation and analysis of phage-specific protein synthesis show that, under restrictive conditions, nonsense mutants in gene A do not block the synthesis and activity of the B protein and nonsense mutants in gene B do not affect the gene A function. The map position of the COOH-terminal end of gene A was determined using an amber mutant that synthesizes slightly shortened A and A proteins. It is concluded from these experiments that gene A overlaps gene B completely (or almost completely) and that the overlap region can be translated in two ways with different reading frames: one frame for the synthesis of the A and A proteins and another for the synthesis of the B protein.


Maintenance of genetic variability under mutation and selection pressures in a finite population.

Formulas are developed for the distribution of allele frequencies and the mean and variance of heterozygosity under mutation and selection pressures. In large populations, even slight selection drastically changes the shape of the distribution of allele frequencies and reduces heterozygosity. On the other hand, the number of rare alleles in a sample is much less affected by selection. Under genic selection, heterozygosity may decrease with increasing population size. As a test statistic, the variance of heterozygosity can be used to detect the presence of selection, though it is not efficient when selection is very slight.


Decay of genetic variability in geographically structured populations.

The ultimate rate and pattern of approach to equilibrium of a diploid, monoecious population subdivided into a finite number of equal, large, panmictic colonies are calculated. The analysis is restricted to a single locus in the absence of selection, and every mutant is assumed to be new to the population. It is supposed that either the time-independent backward migration pattern is symmetric in the sense that the probability that an individual at position x migrated from y equals the probability that one at y migrated from x, or it depends only on displacements and not on initial and final positions. Generations are discrete and nonoverlapping. Asymptotically, the rate of convergence is approximately (I-u)2t[I-(2NT)-1]t, where u, NT, and t denote the mutation rate, total population size, and time in generations, respectively; the transient part of the probability that two homologous genes are the same allele is approximately independent of their spatial separation. Thus, in this respect the population behaves as if it were panmictic.


On the location of palindromes in immunoglobulin genes.

We present a statistical method for detection of palindromes in mRNA or DNA, starting from the protein sequence. Analysis of immunoglobulin genes by this method demonstrates that palindromic sequences are not randomly distributed. They are located at each side of the hypervariable regions in the variable (V) genes, whereas no such regular design is observed in the constant (C) genes. In addition, palindromic sequences overlap the V-C junction in all immunoglobulin classes and significant palindromes are present near residue 216 of the heavy chain, which is the end of deletions in many heavy chain diseases. The relevance of these palindromes to gene translocation and generation of diversity in antibodies is discussed.


Conversion of incomplete antibodies to direct agglutinins by mild reduction: evidence for segmental flexibility within the Fc fragment of immunoglobulin G.

Reduction of interchain disulfide bonds converted some IgG incomplete antibodies to direct hemagglutinins. This conversion occurred whether antibody was free in solution or bound to the red-cell surface. Reduced antibody permitted to reoxidize in air no longer behaved as a direct agglutinin; reversion to an incomplete antibody did not occur when reoxidation was prevented by S-alkylation. These results suggest that mild reduction of the antibody imparts sufficient freedom to permit bridging between cells and are interpreted as evidence that the interheavy-chain disulfide bonds restrict segmental flexibility within the Fc fragment of IgG.


Kinetics of cell death and disintegration in human lymphocyte cultures.

In order to quantitate lymphocyte proliferative responses, we explored the role of cell death in the kinetics of phytohemagglutinin-stimulated cultures. Unless the disintegration time (tDIS) of nonviable lymphocytes in culture is known, the rate of cell death cannot be calculated. To obtain tDIS, we determined the time interval between total and viable cell population decay after various killing events. Two subpopulations of lymphocytes were observed, the major (80%) with a mean (+/-SEM) tDIS of 16+/-2 hr and the minor (20%) with a tDIS of 45+/-7 hr. Kinetic balance sheets were constructed predicting total culture DNA content (cells plus medium), as calculated both from proliferation rates and from observed death and disintegration rates. In an experiment characterized by extensive cell death, the two tallies were well-matched when the above data were utilized. The large discrepancy between predicted and observed DNA contents of the medium indicates that the DNA of disintegrated lymphocytes is extensively degraded. We conclude that cell death explains proliferation deficits in stimulated lymphocyte cultures. Our approach to quantitation of cell death may have general applicability to kinetic studies of cultured cells.


Ligands and oxidants in ferrihemochrome formation and oxidative hemolysis.

We have investigated the effect of size of a single neutral ring substituent on the induction of hemolytic anemia and the formation of a ferrihemochrome by substituted phenylhydrazines. The severity of induced anemia decreased with increase in size of a halogen atom or an alkyl group ortho to the hydrazino group, little anemia resulting from 2-iodophenylhydrazine and no anemia from 2-tert-butylphenylhydrazine. The size of a halogen atom or an alkyl group at the meta or para position had relatively little effect on the severity of induced anemia. The ability of an arylhydrazine to induce hemolytic anemia paralleled its ability to produce a ferrihemochrome with an exogenous ligand, probably the corresponding aryldiazene. In general, rapid and complete formation of ferrihemochrome occurred with arylhydrazines that induced severe anemia. The degree of hemolysis induced by an arylhydrazine was not related to its rate of autooxidation, i.e., the rate at which oxidants are formed by the reduction of oxygen. We propose a mechanism of arylhydrazine-induced oxidative denaturation based on the simultaneous formation of hydroxyl radical and aryldiazene ferrihemochrome in a reaction of oxyhemoglobin with arylhydrazine. We suggest that after oxidation of the porphyrin ring is initiated by a hydroxyl radical, oxidative cleavage of the ring is facilitated by the presence of a large ligand in the heme crevice. Thus, aryldiazene ferrihemochrome may contribute to instability in a hemoglobin molecule, whereas globin ferrihemochrome results from instability.


Sex differences in response to hepatitis B infection among patients receiving chronic dialysis treatment.

Patients undergoing treatment at a community-based renal dialysis clinic were monitored monthly for hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). Of 160 patients who began treatment HBsAg(-)/anti-HBs(-), 77 subsequently became HBsAg(+). Once HBsAg(+), males were more likely to remain HBsAg(+) indefinitely, whereas females were more likely to convert to HBsAg(-) and develop anti-HBs. This was not due to a sex difference in exposure to hepatitis B virus because only patients who became infected while undergoing treatment were included in the analysis. These data are clear evidence of a sex difference in response to hepatitis B virus, which may partially explain the greater incidence of several chronic liver diseases, including primary hepatocellular carcinoma, in males.


Neuronal actions of endorphins and enkephalins among brain regions: a comparative microiontophoretic study.

The brain peptides alpha- and beta-endorphin, leucine- and methionine-enkephalin, as well as the opiate normorphine, have been evaluated by microiontophoresis for their effects on neuronal activity in several regions of the rat brain. In cerebral cortex, brainstem, caudate nucleus, and thalamus, most responsive cells were inhibited by the peptides and by normorphine, while in hippocampus all responsive cells were excited. Both inhibitory and excitatory responses were blocked by the narcotic antagonist naloxone. Occurrence of responsive cells encountered in a particular region was loosely correlated with density of stereospecific opiate binding sites as reported by others. These results are consistent with the hypothesis that the endorphins and enkephalins may represent a new class of central neurotransmitters; among other functions, these peptides may play a role in the regulation of behavior and the expression of psychopharmacological agents such as the opiate alkaloids.