Genetic and epidemiologic studies of oral characteristics in Hawaii's schoolchildren: V. Sibling correlations in occlusion traits. Sibling correlations with adjustment for age, sex, and other covariates showed the highest degree of similarity in incisor width, followed by malalignment, overjet, overbite, crowding, spacing, and crossbites. The smallest intrafamily correlations were observed in the variables in buccal segment relationship, especially in neutroclusion and idealized occlusion pattern.


Glucose transport in Streptococcus mutans: preparation of cytoplasmic membranes and characteristics of phosphotransferase activity. Cytoplasmic membranes from Streptococcus mutans were used to study phosphoenolpyruvate (PEP)-dependent glucose transport. The Km values for glucose and PEP were 0.3 and 0.4 mM. The system was sensitive to sulfhydryl reagents and detergents. The nonmetabolizable analogue 2-D-deoxyglucose was readily phosphorylated while alpha-methyl-glucose and 3-0-methylglucose were inefficiently derivatized. The fermentable sugars fructose, galactose, mannitol, and sorbitol were phosphorylated at reduced rates.


Fracture mechanics of dental poly (methyl methacrylate). Strength characteristics of dental poly(methyl methacrylate) were studied in terms of the fracture surface energy and inherent flaw size, using the methods of Berry.2-9 Dental poly(methyl methacrylate) is weaker than the corresponding bulk polymer because the former has a lower energy and higher inherent flaw size.


Reinforced polycarboxylate cements.

Reinforced polycarboxylate cements. Mechanical properties of polycarboxylate cements are greatly improved by incorporation of high modulus fibers such as potassium titanate into acrylic-itaconic acid and acrylic-itaconic-acronitic acid copolymers. Other desirable properties of the cements are not changed by the addition of fibers.


Dental field theory: an application to primate evolution. A major complicating factor in using dental data in analyses of taxonomic and evolutionary problems is the existence of morphogenetic fields. Efforts are made to abstract tooth crown size morphogenetic fields of the orangutan. The utility of coefficients of variability and factor analysis, to this end, is presented. Resulting morphogenetic dental crown size fields are described and related to hominoid dental evolution.


Instrumental evaluation of mouth odor in a human clinical study. Gas chromatography and a flame photometric detection system measured directly from mouth air the sulfur volatiles associated with malodor. Statistically significant reductions in the hydrogen sulfide and methyl mercaptan levels were observed with use of the test rinse vs a placebo rinse. The method appears potentially useful in objective clinical evaluation of mouth odor.


Specificity and some physical properties of cathepsin D from bovine uterus and dental pulp. The action of uterine cathepsin D on the insulin A-chain (S-sulfo) and porcine glucagon was compared with the action of bovine dental pulp cathepsin on the same substrates. Differences observed with respect to molecular and catalytic properties suggest that different gene products (coding for the same function) are used during cell differentiation.


Effect of single versus fractionated doses of x-radiation on incisors in rats. This study compares the effect of single vs fractionated doses of X-radiation on the incisor of the rat. The results showed that fractionated doses are more damaging than a single dose and that three fractionated doses have a stronger effect than five.


Cellular responses to dental amalgam in vitro. Cytotoxicity of fine cut amalgam was persistent until 24 hours after trituration in vitro, whereas cytotoxicity of spherical amalgam diminished more quickly. Increasing mercury content in spherical amalgam increased cytotoxicity. Possible reactions for the diminution of cytotoxicity of amalgams with time are discussed.


Relationship between dental school performance and preprofessional major courses of study. This study examined the records of dental students in the class of 1969 at the university of Pittsburgh School of Dental Medicine, in an attempt to determine statistically what preprofessional major was the best predictor of academic success in dental school. In the sample studied, no differences were found among the four groups-when they compared on the variable, dental school grade point average. These data suggest that the selection of the preprofessional major course of study may bear little relationship to academic performance in dental school.


Survey of undergraduate endodontic curricula. A survey of undergraduate endodontic curricula in 67 United States and Canadian schools has been carried out. The response rate was 82%, with 2 of the 53 responses being incomplete. The major findings were as follows: 1. There was an extremely wide range in curriculum hours, but the average number of clock hours (46 hours) for the preclinical lecture and laboratory period compared favorably with the minimum recommended in 1965.' 2. The average of about six teeth treated during the clinical period also compared favorably with the minimum recommended in 1965.' 3. The average time required for each clinical case (11 hours per tooth) might suggest a critical reevaluation of teaching methods and philosophy.


Objective evaluation of quality in cavity preparations. Significant improvements in reliability of criteria measures were obtained by using a newly developed instrument to evaluate objectively the quality of cavity preparations in comparison to subjective ratings by the instructors of the quality of cavity preparations.


Effects of high altitude and hypophagia on mineral metabolism of rats. Electrolyte excretion and balance were compared in meal-eating, adlibitum-fed rats maintained in Denver (1,600 m) and on Pikes Peak (4,300 m) and in meal-eating rats maintained in Denver but pair-fed to the Pikes Peak animals. Most of the changes in excretion and balance at Pikes Peak were attributable to hypophagia. At both elevations, equivalent decrements in mineral intake led to nearly equivalent decrements in mineral excretion. Comparisons of the Pikes Peak and Denver pair-fed animals, however, revealed certain changes that were unique to high altitude. These included a marked and sustained reduction in ammonia excretion over the 13-day period of exposure. The higher elevation also produced an enhanced sodium excretion on day 1 of exposure and a reduced sodium balance over the first 6 days. Potassium balance showed no changes unique to high altitude during the first 6 days on Pikes Peak but was significantly reduced during week 2 of exposure. The urinary sodium:potassium ratio was elevated during the first 4 days at 4,300 m, but this effect was attributable to altitude on day 1 only. Enhanced calcium and magnesium excretions, relative to those observed in the pair-fed rats, were observed over the middle and latter portions of the exposure period. The balance of these two minerals showed no altitude-dependent effects. Chloride and phosphate excretions showed an altitude-dependent reduction during day 1 and week 1 of exposure, respectively. These changes were associated with more positive balances. It is concluded that the altitude-dependent effects on mineral metabolism are largely, if not entirely, attributable to hypocapnia and associated alkalosis.


Complications associated with maxillary osteotomies. There are certain complications involved in maxillary ostetomies; devitalization of teeth, loss of part or all of the osteotomized segment, and relapse are possible problems. The paramount cause of the complications in seven different cases seemed to be the interruption of the blood supply to the operative site. A seven-point guideline is formulated; it integrates preoperative planning, surgical procqedures, and postoperative care.


Intraoral biopsy of the parotid gland.

Intraoral biopsy of the parotid gland. Although biopsy of the parotid gland is occasionally necessary for diagnostic purposes, surgeons hesitate to perform a biopsy because of the possible adverse effects, such as facial scarring or damage to facial nerves. An intraoral technique was used for biopsy of a parotid gland of a young woman. The procedure was successful; a diagnosis was made and there was no facial scarring. The potential hazards must be weighed against the benefits.


Mandibular atrophy: a theory of its cause and prevention. The unconscious habit of holding the teeth together or clenching, or both, is one of the most dominant factors that leads to  mandibular atrophy. This habit causes long periods of mucoperiosteal ischemia due to denture pressure, with inflammation, a lowered PH, and a net bone loss. Pressure resorption is postulated as the primary cause of mandibular atrophy.


Oronasal fistula following anterior maxillary osteotomy. A complication of oronasal fistula secondary to anterior maxillary osteotomy occurred; it was successfully treated after two attempts at closure.


Multiple facial trauma complicated by occlusion of the internal carotid artery. The occurrence of thrombosis of the internal carotid artery is a rare entity. Such a case, in association with multiple facial fractures, has been presented. The management of the patient was complicated by neurological disturbances that affected definitive treatment. This case illustrates the importance of close monitoring of all patients with facial trauma before, during, and after surgery.


Trichinosis associated with oral squamous cell carcinoma: report of three cases. Three patients with oral squamous cell carcinoma had Trichinella larvae in the associated oral soft tissues. Cocarcinogenesis may be involved in the interrelationship between  trichinosis and oral squamous cell carcinoma.


Submandibular duct sialolith of unusual size and shape. An unusual sialoith within Wharton's duct was associated with an abscess of the submandibular space. Previously reported sialoiths of considerable size are reviewed, and etiology, symptomatology, and surgical removal are discussed. Emphasis is placed on the need for thorough examination of patients who have symptoms of sialoithiasis in an attempt to locate the sialolith before it assumes unusual dimensions.


Bone healing and revascularization after total maxillary osteotomy. Adult rhesus monkeys were used as experimental analogues to investigate vascularization, revascularization, and bone healing associated with total maxillary osteotomy. Microangiographic and histologic studies showed minimal transient vascular ischemia, minimal osteonecrosis, and early osseous union. Transection of the greater palatine arteries had no discernible effect on the circulation to the teeth and bone in  the maxilla and its enveloping soft tissues. The results of experiments in animals and clinical studies indicate that palatal mucosa and labial-buccal gingiva provide an adequate nutrient pedicle for single-stage total maxillary osteotomies.


Reimplantation of freeze-treated mandibular bone. Mandibular bone devitalized by freezing after removal from the body and subsequent reimplantation was observed for its potential to act as a framework of new bone formation. Clinical union and bony replacement occurred when the reimplanted bone was covered by healthy, well-vascularized soft tissue. New bone initially formed subperiosteally along the devitalized bone. Later specimens showed increased production of endosteal bone. The results suggest that a resected mandible subjected to freezing might be immediately reimplanted as a graft when the mandible is involved as part of a radical operative procedure. Further studies are indicated to evaluate this potential when the periosteal covering is removed.


Intraoral junctional nevus: review of the literature and report of case. Pigmented nevi are uncommon in the oral cavity in comparison to their frequency on the skin. The junctional variety is extremely rare; it accounts for approximately 4% of reported intraoral nevi. Another case of intraoral junctional nevus is added to the literature. A review and a discussion of cellular nevi are presented and the realtionship of junctional nevi to malignant melanoma is considered. Regardless of the appearance of the lesion, wide surgical excision is recommended for all pigmented lesions within the oral cavity.


Treatment of temporomandibular joint ankylosis with methyl methacrylate interpositional arthroplasty: reprot of four cases. Four cases of interpositional TMJ anthroplasty are presented. All patients had been operated on previously. The initial success was compromised by reunion of the proximal and distal surgical sites. These failures were due to inadequate gap arthroplasty; lack of complete coverage of the superior distal stump; or lack of retention of the alloplast at the site of placement. The case of manipulation and good tissue tolerance of methyl methracrylate make it an excellent material for interpositional arthroplasty.


Hyperbaric oxygen treatment of mandibular osteomyelitis in osteopetrosis. A patient was successfully treated with hyperbaric oxygen for chronic osteomyelitis of the mandible associated with osteopetrosis. This mode of therapy appears to have a definite place in the management of such patients. There was no clinical, radiographic, or laboratory evidence that the osteopetrosis was made worse by the hyperbaric oxygen.


Cementoblastoma of the maxilla: report of case. A case of cementoblastoma of the maxilla has been presented. The lesion is considered unusual because of its location size, and close association with the cementum of the root of the tooth.


Colitis after clindamycin therapy.

Colitis after clindamycin therapy. Colitis developed in a young patient who was receiving clindamycin as part of the management of pericoronitis. Vigorous treatment of the colitis became necessary. The case and the recent literature that has dealt with this potentially very serious complication of lincomycin and clindamycin therapy are reviewed. The dental profession should become aware of this dangerous side effect and exercise caution in prescribing any medication that could produce such a serious outcome.


An investigation of the clinical and histologic effects of selected dentifrices on human palatal mucosa. A study was undertaken in 24 human volunteer subjects to determine the possible effects of selected commercially available dentifrices on clinically normal masticatory mucosa. An acrylic stent was fabricated which was designed to hold four test dentifrices in close apposition to the palatal tissues for 1 hour. Evaluation approximately 8 hours later revealed pathologic responses which were evident clinically and histologically. 1. Clinically, palatal tissues exposed to Crest were not distinguishable from control areas, while Colgate (mfp), MacCleans, and Ultra Brite produced erythematous changes which were statistically significant when compared with adjacent control sites. 2. Histologically, epithelial changes were seen within the test sites which ranged from a parakeratin-like surface layer to necrosis and intraepithelial abcess formation. Control sites consisted of normal orthokeratinized palatal mucosa in all cases. 3. The more severe microscopic reactions were noted with MacCleans and Ultra Brite, while the milder reactions were associated with Colgate (MFP). Crest infrequently produced a parakeratin-like response. The response was not statistically significant when compared with controls. 4. The clinical and histologic reactions were generalized throughout the test population, suggesting that the responses were not due to individual hypersensitivity but due to irritation from one or more of the dentifrice components. Although the clinical significance of these findings could not be readily assessed, the potential for irritation of human palatal mucosa by selected dentifrices has been demonstrated. These findings support the suggestion by the World Workshop in Periodontics (1966)20 that efforts should be directed to the development of dentifrice materials less harsh to the oral tissues.


A long term clinical study evaluating the effect of two dentifrices on oral tissues. 1. A long term (54 months) supervised, double-blind human clinical study has been conducted to ascertain whether the routine use of a commercially available cosmetic dentifrice, with purported stain removal and flavor impact characteristics, would cause adverse manifestations in the oral tissues, as compared to the similar use of a more conventional type of commercially available dentifrice. 2. One hundred and twenty male and female subjects (aged 12 to 70) were randomly assigned to the use of one of the two dentifrices under investigation, after which they used the assigned dentifrices twice daily (1 min each brushing) under supervised conditions for a period of 54 months. 3. Clinical examinations were conducted on all subjects initially (base line), and at 3-month intervals throughout the 54-month course of the study. This examination included a complete and thorough inspection of the oral soft and hard tissues. 4. The results after 54 months of continuous use of the dentifrices (representing a total dentifrice/oral tissues exposure time of approximately 45 hours per subject) indicated that neither of the two dentifrices caused any adverse reactions of the oral soft tissues and that both dentifrice groups had similar patterns and levels of cervical abrasion and/or erosion. 5. The results also indicate a lack of direct correlation between laboratory abrasivity values (as determined by a radioactive dentin abrasion procedure) and the clinical situation, thus suggesting that factors other than dentifrice abrasivity may play an important role with regard to tooth wear.


Primate model for testing periodontal treatment procedures: I. Histologic investigation of localized periodontal pockets produced by orthodontic elastics. Experimental periodontal lesions have been produced in Rhesus monkeys using orthodontic elastics. These lesions are characterized by an irreversible apical positioning of the junctional epithelium and both horizontal and angular bone loss. It was concluded that this lesion is suitable for testing the effect of periodontal treatment.


A form and function concept of occlusion and the maxillomandibular relationship. A fixed retruded positional concept for the mandible is traceable historically to early dental prosthodontic attempts to obtain duplicable interocclusal records. The original method, derived for relating the maxillary and mandibular jaws for edentulous patients, later gained acceptance as a physiologic entity for patients with teeth as well as for those who were edentulous. Ultimately, static centric relation led to entirely reproducible systems, involving all mandibular movements, which endeavored to match occlusal contacts with a fixed condylar envelope of motion. A fixed or static interpretation of centric relation has become the common touchstone for virtually all the subspecialties of dentistry, regardless of the relative matching and spatial relationships of the jaws,and, as such, misdirects diagnosis and treatment. An attempt has been made to demonstrate that the temporomandibular articulation has a wide range of adaptability as well as a remodeling capacity  and that it assumes its position as a result of the interplay of intercuspation of teeth and the neuromusculature. A dynamic concept of centric relation is presented as a quasifixed position of temporary duration which exists in the form of an equilibrium established by the balance of the neuromusculature and ligaments. The adoption of a dynamic or alterable concept of centric relation allows for diagnosis and treatment which is rationalin theory and workable in fact.


Construction of an acrylic resin articulator mounting platform. A technique is presented for constructing an articulator mounting platform for maxillary casts. It simplifies and standardizes the mounting procedure.


Anteroposterior position of "Myo-Monitor centric". Nine patients had interocclusal recordings made at "Myo-Monitor centric", centric occlusion, and centric relation. With the use of centric relation as a reference point, the anteroposterior distances from centric relation to centric occlusion and Myo-Monitor centric were measured. In addition, the variations in Myo-Monitor centric were analyzed by making repeated interocclusal records on the same patient. Results showed that, within the limits of this study, Myo-Monitor centric was anterior to centric relation but was slightly retrusive to centric occlusion. Also, Myo-Monitor centric recordings were variable from the left and right sides of the same patient and varied on the same side of the same patient.


The effects of variations in the opposing dentition on changes in the partially edentulous mandible. Part II. Densitometric measurements. Distal-extension lower removable partial dentures were used to study the effects of various types of opposing dentitions on the residual mandibular ridge. The opposing-dentition groups included complete upper dentures, removable partial upper dentures, and natural teeth. Changes in the bone of the lower residual ridge were measured by means of densitometry. A significant densitometric difference was found in the bone of the partially edentulous mandible between the group of subjects wearing complete upper dentures and the group with natural upper teeth. The reason for this difference is uncertain; however, several theories can be offered. These are (1) an inherent bone difference between the subjects in the two groups, implying a difference in the bone of the group that retained their natural upper teeth longer than did the complete denture group, (2) an increased frequency and/or duration of muscle pull on the mandible due to clenching of the teeth to stabilize the upper complete denture, and (3) the possibility of coincidence. None of the densitometric changes measured at +18 months was significant.


Development of a simplified system for clinical evaluation of occlusal interrelationships. Part II. Storage of the information. The development of a simplified system for evaluation of occlusal interrelationships has been discussed in two parts. Part I concerned itself with data obtained from a Patient Questionnaire and through clinical examination. Part II has dealt primarily with the method of transcription of collected information and with data processing keypunch instructions. It is anticipated that this method of data collection will provide the vehicle for an ongoing, broad-base study of occlusal and temporomandibular joint/muscle interrelationships.


Pantographic records on TMJ dysfunction subjects treated with occlusal splints: a progress report. Five subjects with TMJ dysfunction showed difficulty in making reproducible mandibular border movements as recorded by a pantograph. These subjects were treated with occlusal bite splints, and muscle activity was studied by electromyography. After one month of treatment, most subjects showed relief of clinical symptoms and improved EMG muscular activity. Most of the subjects' mandibular movements did not improve to the point of making reproducible border movements on a pantograph. The length of time and the type of treatment may have had a significant effect on the results. This should be investigated further.


Motor pauses in EMG activity during chewing and biting. Biting on hard particles during chewing sometimes produced motor pauses but more often abrupt atypical terminations of the EMG patterns occurred. A series of tests with different experimental biting and chewing situations were performed. The results indicate that the motor inhibition that occurs during biting and chewing mainly are of two different origins. The inhibition that occurs during tooth tapping and biting on hard particles is caused by tendon and muscle stretching occurring as a result of the mechanical stop of the jaw movement. The inhibition occurring when crushing a brittle bolus has a different origin and occurs before tooth contact and is a form of unloading reflex. The periodontal receptors or surface sensibility appears to be of minor importance for these types of motor inhibition.


Oral manifestations in Urbach--Wiethe disease (lipoglycoproteinosis; lipoid proteinosis; hyalinosis cutis et mucosae). The oral manifestations in 27 patients with Urbach--Wiethe disease (UWD) discovered in Northern Sweden are described. The oral regions most frequently affected are the lips, the back of the tongue, the frenulum of the tongue, the palate and the back wall of the pharynx. The general impression is that older patients usually have more marked manifestations than younger, indicating that the oral lesions may become more severe with increasing age. Histopathologically, the disorder is essentially a microangiopathy in which the walls of small blood vessels are thick and PAS-positive, indicating the presence of glycoproteins. In clinically affected regions there are usually PAS-positive extravascular deposits. In material used of lipid histochemical studies, sudanophil droplets were found in the vessel walls. By staining with osmium tetroxide the osmium is--contrary to previous assumptions--in some way bound to the droplets, but for unknown reasons is not reduced to a coloured product. The binding of osmium was demonstrated by the OTAN (osmium textroxide alpha-naphthylamine) method. The exact significance of this finding awaits further studies. The implications of dental anomalies occurring in UWD are discussed.


Index for need of orthodontic treatment. The demands placed on an index for evaluating the need of orthodontic treatment are described. An index designed by the Swedish Medical Health Board is discussed against the background of the above mentioned demands. A new index for the need of orthodontic treatment is presented. It consists of a morphological part in which essential abnormalities are recorded and allotted points according to their severity. The index also has a functional part in which selected functional disorders of the masticatory system as well as occlusal disharmonies are recorded and allotted points. The reasons are given for the choice of the various features included in the index. Practical instructions for the use of the index are given. The new index for need of orthodontic treatment was tried under clinical conditions in two series of children, aged 6--16 years. The variation between the recordings by the same examiner on two occassions was studied by double determinations. With but few exceptions no systematic errors were found between the double determinations. The precision of the new index for need of treatment was found to be the same as of that given by the Swedish Medical Health Board. No systematic differences were found between recordings made by orthodontists and inexperienced examiners. The accidental error of the method was of the same order for orthodontists as for inexperienced examiners. Comparison of recordings made by four orthodontists showed systematic errors between the recordings of functional but not of morphological deviations. Ranking of the children according to the need of orthodontic treatment as judged with the new index differed from that obtained with the system of the Swedish Medical Health Board. The new index attached more importance to functional deviations. This was the main requirement in the construction of the new index.


Citanest Forte--its use in oral surgery. A clinical evaluation of Citanest Forte (brand of prilocaine HCL) was carried out on 3,000 oral surgery patients to determine the effectiveness and safety of the drug. Citanest Forte has been found to be a useful local anesthetic, and the results of this study would indicate that it can be effectively and safely substituted for other local anesthetic solutions currently in use for all routine oral surgery procedures.


Squamous-cell carcinoma of the floor of the mouth with extensive mandibular involvement. The case of a patient with an extensive squamous-cell carcinoma of the floor of the mouth with erosion of the mandibular bone is presented. The history and initial clinical picture were consistent with either carcinoma with superimposed infection or chronic osteomyelitis with an acute exacerbation. A discussion of diagnosis and treatment of carcinoma of the floor of the mouth follows this case report.


Dermoid cyst of the floor of the mouth. Report of a case. Dermoid cysts of the floor of the mouth comprise aproximately 0.01 per cent of all oral cystic lesions. This case is presented because of its large size, its unusual location, and the difficulty encountered in removing the mass.


Osteogenesis within polyethylene implants at fracture gaps. Sterile 7 mm. polyethylene implants were implanted in standard 6 mm. bilateral midfibular fracture gaps in thirty rats (sixty defects), and six rats were used as controls with identical bilateral midfibular fracture gaps. Clinical, radiologic, and histologic studies at a 12-week interval revealed osteogenesis at internal and external surfaces of implants resulting in bony union; however, gaps without implants resulted in fibrous union and nonunion.


Patient's medical status--a factor in dental treatment. A review of the medical questionnaires of 4,785 patients seen at Temple University School of Dentistry from March, 1973, through January, 1974, revealed that chronic illnesses affect all ages. The problems and complexities found in our patients are never-ending entities. The dentist must be cognizant of all these medical aberrations so that, where indicated, consultations with other members of the health sciences can be obtained prior to providing definitive treatment. With this knowledge of the patient's medical status and medications being taken, the dental practitioner can now individualize this treatment prescription. The profession must accept this responsiblity, so that the patient can be aided in maintaining and sustaining his general health.


Oral carcinoma in situ.

Oral carcinoma in situ. Oral carcinoma in situ (CIS) as a histopathologic entity was studied in seventy-seven patients to determine the clinical and histologic parameters of the disease. There were forty-nine male and twenty-eight female patients, with 45.1 per cent of the lesions being described clinically as white, 15.9 per cent as red, and 8.5 per cent as a combination of the two. The high-risk sites for CIS were floor of the mouth (23.2 per cent of all lesions), tongue (22.0 per cent), and lips (in males only, 19.5 per cent). Histologically, there was a considerable range of variation in surface keratinization, thickness of epithelium, and certain cytologic alterations. The most consistent of all cytologic changes was loss of orientation of cells. There is no information available concerning possible regression of oral CIS, as is known for CIS of uterine cervix. Furthermore, there is no information concerning the frequency of or the period of transition from oral CIS to invasive carcinoma or whether all oral carcinoma is preceded by CIS. Further studies on this disease are essential.


Aspects of the fine anatomy of aphthous stomatitis. Samples of human aphthous stomatitis were studied under the electron microscope. The epithelial cells bordering the ulcer present multivesicular bodies, pinocytotic vesicles, primary lysosomes, digestive vacuoles, and autophagic vacuoles. The golgicomplex is noticeably increased; free ribosomes and rough endoplasmic reticulum are abundant. Crystalline structures are close to the nucleus. One or two paranuclear bodies are in most of the nuclei. A frank cell injury is evident, causing a major activity of the digestive cell system; the origin and formation of lysosomes through r.e.r. and the Golgi system are discussed.


Multiple odontogenic tumors and other anomalies. An autosomal dominantly inherited syndrome. The authors report the occurrence of multiple odontogenic tumors in a father, his two sons, and his daughter. These occurred soon after birth and recurred upon occasion, with imcomplete removal. Associated with the multiple odontomas is esophageal stenosis. The occurrence of hepatopathy of unknown origin and an increased susceptibility to infection appear to be other components in this syndrome. A similar case reported in the literature has been cited. Autosomal dominant inheritance is suggested.


Salivary mucoceles.

Salivary mucoceles. A survey of natural mucoceles revealed that there were two types, namely, extravasation and retention, and that extravasation mucocceles occurred most often in younger patients and in the lower lip, whereas retention mucoceles occurred most often in older patients and elsewhere in the mouth.


Benign osteoblastoma.

Benign osteoblastoma. The eighth case of a benign osteoblastoma of the jawbones is presented. The tumor showed early recurrence after imcomplete curettage. The tumor-bearing part of the mandible was resected and reconstructed with an autologous bone graft. The histologic features of the entire specimen proved its benighn character. The patient is doing well 2 years after surgical treatment.


Radicular variety of double dens invaginatus. A rare, previously unreported case of radicular variety of double dens invaginatus is presented. The probable mechanism of formation is discussed.


Oral Kaposi's sarcoma.

Oral Kaposi's sarcoma. A new case of primary oral Kaposi's sarcoma associated with immunosuppressive therapy is presented. The literature related to oral Kaposi's sarcoma is reviewed, and the pathogenesis of this condition is briefly discussed. There is a possiblity that  early lesions of Kaposi's sarcoma may be misadiagnosed clinically and histopathologically as simple pyogenic granulomas.


Periapical tissue reactions after pulp exposure in rat molars. Apical periodontal lesions were produced in the rat molar by exposing the pulp to the oral environment. The natural history of the undisturbed lesion was studied at time intervals ranging from 2 days to 1 year postoperatively. The earliest reactions were usually inflammatory infiltration at the apex. The severity of the lesions was related to the amount of vital pulp still present in the tooth rather than to the time lapse after exposure. After 1 month most pulps has undergone necrosis and the lesions about the apices which followed showed two main types of reaction. In the case of the suppurative reaction, pus drained along a root surface, destroying the periodontal ligament and interradicular bone until it emerged at the gingival sulcus. The sinus tract could become lined with oral epithelium. In the reparative type of reaction, suppuration was absent or minimal and the apices were surrounded by fibrous connective tissue. The fiber bundles occasionally formed a collagenous scar, but they were usually replaced by cementum and bone with a new periodontal ligament. The width of the periodontium was never restored to its normal dimensions. Secondary destruction of the teeth occurred by fracture of cusps followed by caries which started in the exposed pulp chamber. Despite the predominance of destructive factors, spontaneous repair indicated good healing potential of the apical periodontal tissues.


A study of the focal troughs of three panoramic dental x-ray machines. Part I. The area of sharpness. A comparison of three panoramic x-ray machines revealed that the focal trough of the panorex curved inward in the posterior region, that of the GE-3000 remained straight, and that of the Orthopantomograph flared outward. The panorex was found to have the widest trough in the anterior region; the GE-3000 had the widest trough in the posterior regions.


A determination of the minimum radiopacification necessary for radiographic detection of an aspirated or swallowed object. It was hoped that it might be possible to establish some standard or starting point which could be used by future investigators to judge adequate levels of radiopacity of radiopaque denture-base materials. Aluminum and copper were used to define a suitable radiopacity scale. The scale was represented by two sets of specimens--one of regular outline and uniform thickness, the other of irregular shape and tapering thickness. Radiographs of the chest and abdominal regions of a cadaver were exposed, with the specimens placed on the film side and then on the opposite side of the cadaver. The results showed that it was more difficult to locate the beveled irregular specimens, that there was little difference between the chest and the abdomen with respect to ease of locating the same objects, and that the closer an object is to the film the easier it is to locate. For 95 per cent observability, an object should have a level of radiopacity at least equal to that produced by 0.20 mm. of copper.


Correction of severe open-bite associated with muscular disease. Report of a case. A 14-year-old boy presented with a severe open-bite and arch collapse associated with muscular disease. Multiple osteotomies of the maxilla and mandible with autogenous bone grafting were used for surgical closure of the open-bite. A satisfactory and stable skeletal result was achieved. The patient was then referred for orthodontic therapy to achieve a better dental interdigitation and maintenance of the newly created relationship. In severe cases of open-bite multiple osteotomies of the mandible and maxilla may need to be performed in order to accomplish the desired results. These same results may not be ach ieved by any single surgical procedure. The relationship between severe open-bite and muscle diseases needs to be further established. Once these etiologic factors are known, steps could perhaps be taken to alter the maldevelopment of the facial skeleton. Until this happens, the symptoms are best treated by a combination of surgical and orthodontic intervention.


The healing of surgical defects in alveolar bone produced with ultrasonic instrumentation, chisel, and rotary bur. A histologic comparison of the effects of an ultrasonic instrument, a low-speed rotary cutting bur, and a surgical chisel, all used with water coolant, on the rate of healing of dog alveolar bone was made. After reflection of a mucoperiosteal flap, each instrument was used to produce a 3 by 3 by 2 mm. defect in buccal alveolar bone, 3 mm. apical to the alveolar crest and directly overlying the root structure of the right premolar teeth. Dogs were killed immediately following flap replacement with sutures and 3, 7, 14, 28, 56, and 90 days later. Histologic examination of the surgical areas revealed that the bur produced the smoothest surface. At day 3, specimens prepared with the chisel and the ultrasonic instrument exhibited areas of cellular organization along surfaces with the defect and the formation of osteoid in adjacent marrow spaces. At day 7, osteoblastic activity was most pronounced in specimens prepared with the chisel and least in those prepared with the bur. The subsequent rate of healing in later periods appeared histologically to be the best with the use of the chisel, followed closely by the use of the ultrasonic instrument, and the slowest with the bur, the order of which is consistent with the over-all microscopic evaluation of the effect of the three instruments.


Intraoral actinomycosis. Report of five cases. Five intraoral presentations of actinomycetes are recorded, in three of which the infection was almost certainly specifically due to the microorganisms. The importance of careful histopathologic examination is underlined, and the failure in some cases to investigate apparently simple infections bacteriologically is highlighted.


Primary malignant melanoma of the oral cavity. The natural history of malignant melanoma of the oral cavity is discussed with reference to the findings of previous writers, and six additional cases are reported. These demonstrate the considerable variations in detail of the course of the disease while confiriming the difficulty of treatment and the inexorable nature of the condition.


Tuberous sclerosis with gingival lesions. Report of a case. A case of Bourneville-Pringle syndrome with oral manifestations in a 40-year-old woman is described. The oral manifestations of this rare syndrome consist of multiple tumorlike papillomas which are located mainly on the anterior gingivae of the upper jaw. The histologic examination revealed small papillomas.


Sclerotic cemental masses of the jaws (so-called chronic sclerosing osteomyelitis, sclerosing osteitis, multiple enostosis, and gigantiform cementoma. A series of thirty-eight cases of densely sclerotic lesions of the jaws was studied. The lesions were all at least 1.5 cm, in diameter. Pain, drainage, or localized expansion of the jaw was present in two thirds of the patients. Thirty-four of the thirty-eight patients were women, and twenty-five were negros. In fourteen instances, a radiographic survey of the entire jaws was available. Thirteen of these fourteen patients had multiple lesions which were usually symmetrically distributed throughout the jaws. In twenty-four patients radiographs of the lesional area only were available for review. In thirty-four of the thirty-eight cases (89 per cent), the sclerotic masses were interpreted as cementum. Although this condition has previously been described as chronic sclerosing osteomyelitis, sclerosing osteitis, multiple enostosis, or gigantiform cementoma, it appears more appropriate to consider these lesions as part of the spectrum of the benign fibro-osseous lesions of periodontal ligament origin. Four of the sclerotic lesions, which were radiographically indistinguishable from the cemental lesions, consisted only of bone. Two of these appeared to be examples of true chronic sclerosing osteomyelitis, and two may be appropriately designated as enostosis or osteomas.


Fibrous lesions of the skin and mucous membranes which contain stellate and multinucleated cells. Various fibrous lesions of the skin and mucous membranes share the common histologic feature of stellate and multinucleated fibroblasts. These cells are conspicuous under the light microscope because they contain a well-developed, rough endoplasmic reticulum which, because of its high RNA content, stains basophilic. These characteristic cells are a nearly constant feature of the retrocuspid papilla. They are apparent in about half of the fibrous papules of the nose and abundant in about 1 per cent of irritation fibromas. These lesions most likely represent a nonspecific proliferation of the lamina propria or papillary dermis to various stimuli.


Dens evaginatus in the Thai. An evaluation of fifty-one cases. Dens evaginatus in the Thai had not been described previously. The incidence of this abnormality was found to be 1.01 per cent. The male to female ratio was 1:1.83, a figure which is comparable to findings among the Chinese, since the two groups are closely related. The evagination was observed in fifty-one patients, with 133 premolars and one molar being affected. Thirty-six premolar showed periapical pathosis which was classified into clinical and radiographic features. The frequency of affection of the different premolars was described, together with the histologic appearances of the anomaly. Pathogenesis of dens evaginatus in the Thai seems to be uniform, determined by racial and genetic factors.


Basal-cell carcinoma of the vermilion mucosa and skin of the lip. In a series of 652 basal-cell carcinomas, twelve were on the upper lip and five were on the lower lip. Three cases of basal-cell carcinoma located on the vermilion mucosa, with only slight involvement of the contiguous skin at the mucocutaneous junction, are reported. Two were on the lower lip and one on the upper lip. The patients were 74, 81, and 81 years of age. All underwent adequate wide local excision. None of the lesions recurred clinically or metastasized over periods of 41 to 80 months.


Numberous radicular enamel pearls in a premolar of a wild sheep. An unusually large number of enamel pearls were found in a premolar of a wild sheep from Tibet, purported to be the tooth of a Tibetan saint. The enamel pearls show marked preference for the roots.


Radiographic manifestations of a chronic apical rarefying osteitis with an unusual fistulous tract. A case of chronic apical rarefying osteitis in which radiographic examination revealed a circular osteolytic defect extending through the mandible is reported. The defect was well delineated and surrounded by corticated bone, and may have been the result of anatomic or histologic variations of the mandible.


Panoramic roentgen anatomy of the maxillary sinus. A dry maxillozygoma was radiographed with a Panex panoramic unit with lead foil and wires on the anatomic landmarks. The medical border of the maxillary sinus on the pantomogram is seen at the angle of the anterior and medial walls. The lateral border of the maxillary sinus consists of the maximum posterior convexity of the posterior, and medial walls are recognized as anatomic landmarks only when radiopaque materials are attached to individual walls. Most of the anterior and posterior walls of the maxillary sinus are superimposed upon the medial wall in the pantomogram. The anterior wall occupies the lateral third of the maxillary sinus. Anterior, posterior, and medial walls do not appear as anatomic landmarks on the pantomogram.


Xeroderma pigmentosum cells contain low levels of photoreactivating enzyme. Fibroblasts from patients with xeroderma pigmentosum contain low levels of photoreactivating enzyme in comparison to normal cells. Levels vary from 0 (line 1199) to 50 (line 1259) percent of normal. The depressed enzyme levels are not an artifact of low growth rate, age of cell donor, cell culture conditions, assay conditions, the presence of inhibitors, or mycoplasma contamination. We show that human fibroblasts can monomerize pyrimidine dimers in vivo.


Mutations affecting sexual development in Phycomyces blakesleeanus. Although zygospore (mature zygote) formation in P. blakeslleeanus occurs in liquid glucoseglutamate medium, morphological observations are made more easily when cultures are grown on 1-mm-thick agar medium. Zygophores (sexually differentiated hyphae) develop prior to physical contact in crosses of (plus) and (minus) wild types. Zygophores interlock upon contact and then undergo six successive morphological changes to become a zygospore. Mutants with abnormal carotene synthesis exhibit aberrant sexual behavior. Some zygospores do form in crosses of carA mutants and wild types. Only paired zygophores form in crosses of wild type(plus) with car-42(minus), a beta-carotene-accumulating mutant. Zygophores form only on (minus) in crosses of wild type(plus) with carB(minus), carR(minus), carAcarR(minus), and carBcarR(minus) mutants, and only on (plus) in crosses of car-43(plus) with wild type(minus), car-42(minus), and carA(minus) mutants. Zygophores do not form in crosses of car-43(plus) with carB(minus), carR(minus), carAcarR(minus), and carBcarR(minus) mutants. These observations demonstrate that each mating type makes a chemical messenger that stimulates zygophore development in the opposite mating type.


Mitogenic activity of blood components. I. Thrombin and prothrombin. When added to a culture medium of resting confluent chick embryo fibroblasts in the absence of serum, thrombin (EC 3.4.21.5) is able to stimulate DNA synthesis 12 hr later and to cause a substantial increase in cell number over a period of 4 days. As compared to thrombin, prothrombin exhibits low mitogenic activity. However, in the presence of purified Factor Xa (EC 3.4.21.6) and Factor V, prothrombin is converted to thrombin by "thromboplastin activity" supplied by the fibroblasts. Prothrombin, either purified or as a constituent of plasma or serum, may thus be considered to be a reservoir of mitogenic activity in tissue culture unless antithrombin is present in the culture medium in amounts sufficient to neutralize the thrombin formed. By use of a specific inhibitor of proteases, and by separation of prothrombin by absorption on BaSO4, we estimate that the potential mitogenic activity of prothrombin is approximately 30-50% of the total activity that can be obtained by treatment of fibrinogen-free plasma with thromboplastin. In addition to its mitogenic activity, thrombin can also stimulate the migration of cells. These experiments with thrombin illustrate that well-characterized proteases of blood can act as potent mitogens and suggest that they may play a role in the process of wound healing.


A theory of group selection.

A theory of group selection. In organisms possessing a dispersal phase the processes of mating, competition, feeding, and predation are often carried out within "trait-groups," defined as populations enclosed in areas smaller than the boundaries of the deme. A simple model shows that this can lead to the selection of "altruistic" traits that favor the fitness of the group over that of the individual. The extent of group selection that occurs depends mainly on the variation in the composition of genotypes between trait-groups. The traditional concepts of group and individual selection are seen as two extremes of a continuum, with systems in nature operating over the interval in between.


Nonrandom chromosomal abnormalities in hematologic disorders of man. A nonrandom pattern of chromosomal abnormalities occurs in bone marrow cells obtained from patients with hematologic disorders who have an abnormal karyotype involving a C group chromosome. An additional number 8 chromosome is the most common abnormality, found in more than one-half of the patients studies. An additional number 9 chromosome and the loss of all or part of a number 7 are abnormalities that occur more often than might be expected by chance. It is proposed that specific human chromosomal abnormalities may be related to different specific etiologic agents.


Bovine factor X1 (Stuart factor). Primary structure of the light chain. The amino-acid sequence of the light chain of bovine factor X1 is presented. The sequence of 112 of the 140 residues was determined automatically on fragments produced by specific cleavage of arginyl, glutamyl, tryptophanyl, and asparaginyl-glycine bonds. The remainder was determined by conventional procedures. The amino-terminal sequence of the light chain is homologous with the amino-terminal region of bovine prothrombin and, like the latter, appears to contain several residues of a recently discovered unusual amino acid, lambda-carboxy-glutamic acid. The role of this amino acid in the calcium-binding ability of factor X and prothrombin is discussed.


Evidence for de novo production of self-replicating and environmentally adapted RNA structures by bacteriophage Qbeta replicase. Highly purified coliphage Qbeta replicase when incubated without added template synthesizes self-replicating RNA species in an autocatalytic reaction. In this paper we offer strong evidence that this RNA production is directed by templates generated de novo during the lag phase. Contamination of the enzyme by traces of RNA templates was ruled out by the following experimental results: (1) Additional purification steps do not eliminate this RNA production. (2) The lag phase is lengthened to several hours by lowering substrate or enzyme concentration. At a nucleoside triphosphate concentration of 0.15 mM no RNA is produced although the template-directed RNA synthesis works normally. (3) Different enzyme concentrations lead to RNA species of completely different primary structure. (4) Addition of oligonucleotides or preincubation with only three nucleoside triphosphates affects the final RNA sequence. (5) Manipulation of conditions during the lag phase results in the production of RNA structures that are adapted to the particular incubation conditions applied (e.g., RNA resistant to nuclease attack or resistant to inhibitors or even RNAs "addicted to the drug," in the sense that they only replicate in the presence of a drug like acridine orange). RNA species obtained in different experiments under optimal incubation conditions show very similar fingerprint patterns, suggesting the operation of an instruction mechanism. A possible mechanism is discussed.


A nonidentifiability aspect of the problem of competing risks. For an experimental animal exposed to k greater than 1 possible risks of death R1, R2, ..., Rk, the term i-th potential survival time designates a random variable Yi supposed to represent the age at death of the animal in hypothetical conditions in which Ri is the only possible risk. The probability that Yi will exceed a preassigned t is called the i-th net survival probability. The results of a survival experiment are represented by k "crude" survival functions, empirical counterparts of the probabilities Qi(t) that an animal will survive at least up to the age t and eventually die from Ri. The analysis of a survival experiment aims at estimating the k net survival probabilities using the empirical data on those termed crude. Therorems 1 and 2 establish the relationship between the net and the crude probabilities of survival. In particular, Theorem 2 shows that, without the not directly verifiable assumption that in their joint distribution the variables Y1, Y2, ..., Yk are mutually independent, a given set of crude survival probabilities Qi(t) does not identify the corresponding net probabilities. An example shows that the results of a customary method of analysis, based on the assumption that Y1, Y2, ..., Yk are independent, may have no resemblance to reality.


Slow evolutionary loss of the potential for interspecific hybridization in birds: a manifestation of slow regulatory evolution. Birds have lost the potential for interspecific hybridization slowly. This inference emerges from protein comparisons made on 36 pairs of bird species capable of hybridization. Micro-complement fixation tests show that hybridizable pairs of bird species differ by an average of 12 units of albumin immunological distance and 25 units of transferrin immunological distance. As these proteins evolve at a known and rather steady rate, it is inferred that the average hybridization species pair diverged from a common ancestor about 22 million years ago. The corresponding period for frog species pairs capable of hybridization is about 21 million years, while for hybridizable placental mammals it is only 2 to 3 million years. Thus birds resemble frogs in having lost the potential for interspecific hybridization about 10 times as slowly as have mammals. Birds have also been evolving very slowly at the anatomical level, particularly within the last 25 million years, according to Simpson, Romer, and many other vertebrate zoologists. In this respect they resemble frogs and differ from placental mammals, which have been undergoing unusually rapid anatomical evolution. Chromosomal evolution is also thought to have proceeded very slowly in both birds and frogs, relative to mammals. The above observations are consistent with the hypothesis that evolutionary changes in regulatory systems, that is, changes in the patterns of gene expression, provide the basis for both anatomical evolution and the evolutionary loss of hybridization potential.


Temperature-sensitive mutants of chemically transformed epithelial cells. The first temperature-sensitive mutants of epithelial cells transformed with chemical carcinogens have been isolated. Like the wild-type transformed parental cells, the mutants readily grow in agar suspension at 36 degrees, but in contrast to the wild type, they do not do so at 40 degrees. Detailed studies of one of these mutants, TS-223, indicate that at high temperature it also has reduced cloning efficiency in monolayer culture and a lower saturation density. Scanning electron microscopy revealed that at 40 degrees confluent cultures of TS-223 consist of a monolayer of generally flat polygonal cells, whereas 36 degrees cultures contain many patches of piled-up cells that are spherical and have rougher surface membranes. All of these cellular changes are reversible with upward or downward temperature shifts. The temperature-sensitive lesion appears to reside in a host cell gene which modulates expression of the transformed cell phenotype. These mutants may provide a useful system for elucidating the minimal biochemical changes required for expression of the transformed phenotype in epithelial cells.


Xeroderma pigmentosum cells with normal levels of excision repair have a defect in DNA synthesis after UV-irradiation. Cells cultured from most patients suffering from the sunlight-sensitive hereditary disorder xeroderma pigmentosum are defective in the ability to excise ultraviolet light (UV)-induced pyrimidine dimers from their DNA. There is, however, one class of these patients whose cells are completely normal in this excision repair process. We have found that these cells have an abnormality in the manner in which DNA is synthesized after UV-irradiation. The time taken to convert initially low-molecular-weight DNA synthesized in UV-irradiated cells into high-molecular-weight DNA similar in size to that in untreated cells is much greater in these variants than in normal cells. Furthermore, this slow conversion of low to high-molecular-weight newly synthesized DNA is drastically inhibited by caffeine, which has no effect in normal cells. Two cell lines from classes of xeroderma pigmentosum that are defective in excision-repair show intermediate effects, with regard to both the time taken to convert newly synthesized DNA to high molecular weight and the inhibition of this process by caffeine.


Demonstration of the rapid action of pure crystalline 1 alpha-hydroxy vitamin D3 and 1 alpha,25-dihydroxy vitamin D3 on intestinal calcium uptake. The biological effects of crystalline 1alpha-hydroxyvitamin D3 and crystalline 1alpha,25-dihydroxyvitamin D3 have been compared on the intestinal uptake of calcium-45 by everted duodenal gut sacs from rachitic rats. Peak calcium-45 uptake was observed 1 hr after intravenous administration and both crystalline vitamin D2 analogs were of comparable potency. The rapid onset of calcium-45 uptake and the rapid attainment of maximal calcium-45 transport suggests a direct effect of these crystalline analogs on the mucosal membranes of the intestinal cell.


A cycle of deprotonation and reprotonation energizing amino-acid transport? Although lowering the pK2 of neutral amino acids only weakens their concentrative uptake by Ehrlich cells, the same change greatly enhances uptake of diamino acids. This effect does not arise merely from putting the distal amino group in its uncharged form, but depends on an enhanced deprotonation of the alpha-amino group. Parallel effects are seen for the transport system for basic amino acids, for which the assignment of pK values within the membrane is less ambiguous. To explain the paradoxical advantages of having the alpha-amino group protonated yet readily deprotonated, we propose that a proton withdrawn from that group is pumped over an intramembrane interval to energize amino-acid transport.


Recombinant DNA molecules of bacteriophage phi chi174. Phi chi174 DNA structures containing two different parental genomes were detected genetically and examined by electron microscopy. These structures consisted of two monomeric double-stranded DNA molecules linked in a figure 8 configuration. Such DNA structures were observed to be formed preferentially in host recA+ cells or recA+ cell-free systems. Since the host recA+ allele is required for most phi chi174 recombinant formation, we conclude that the observed figure 8 molecules are intermediates in, or end products of, 1 phi chi174 recombination event. We propose that recombinant figure 8 DNA molecules arise as a result of "single-strand aggression," are stabilized by double-strand "branch migration," and represent a specific example of a common intermediate in genetic recombination.


Re-evaluation of Sepharose-insulin as a tool for the study of insulin action. The biological activity of Sepharose-insulin in different assays in vitro, e.g., stimulation of glucose oxidation, lipogenesis, and antilipolysis and activation of pyruvate dehydrogenase (EC 1.2.4.1) activity, has been investigated. According to amino acid analysis, between 270 and 330 mug (6.9-8.2 U) of insulin were coupled per ml of packed beads. Related to the total insulin content, 0.2-0.7% of the insulin was biologically active. Comparable biological activity was observed with isolated fat cells and fat pad pieces. After incubation with tissue or cells, Sepharose-insulin particles were separated by centrifugation from the medium. The clear supernatant was assayed for biologically and immunologically reactive insulin and contained soluble insulin activity. A quantitative evaluation of the soluble biological and immunological insulin activity in the supernatant accounted for the total insulin activity of Sepharose-insulin.


Human globin gene expression and linkage in bone marrow and fetal liver. During embryonic development there is a transition from embryonic and fetal to adult beta-type globin chains. The high-molecular-weight RNA found in nuclei from embryonic and adult human erythropoietic tissues, fetal liver, and bone marrow, have been investigated for the presence of gamma(fetal)- and beta(adult)-globin messenger RNA sequences by molecular hybridization. Unlike alpha- and beta-globin mRNA sequences, gamma-globin mRNA sequences are absent from both total and high-molecular-weight nuclear RNA isolated from adult bone marrow. The amount of cytoplasmic gamma-globin mRNA is proportional to the level of gamma-chain synthesis, demonstrating that translational control is not a major control mechanism in the expression of globin genes. Since the gamma-, delta-, and beta-globin genes are known to be closely linked genetically, transcriptional control can discriminate between similar gene sequences that are spatially adjacent to one another.


Tay-Sachs' and Sandhoff's diseases: the assignment of genes for hexosaminidase A and B to individual human chromosomes. The techniques of somatic cell genetics have been used to establish the linkage relationships of loci coding for two forms (A and B) of hexosaminidase (EC 3.2.1.30; 2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase) and to determine whether a structural relationship exists between these forms. In a series of human-mouse hybrid cell lines, hexosaminidase A and B segregated independently. Our results and those reported by other investigators are used to analyze the proposed structural models for hexosaminidase. We have also been able to establish a syntenic relationship between the gene locus responsible for the expression of hexosaminidase A and those responsible for mannosephosphate isomerase and pyruvate kinase-3 and to assign the gene for hexosaminidase B to chromosome 5 in man. There is thus a linkage between specific human autosomes and enzymes implicated in the production of lipid storage diseases.


A mechanism to activate branch migration between homologous DNA molecules in genetic recombination. A mechanism to activate branch migration between homologous DNA molecules is described that leads to synapsis in genetic recombination. The model involves a restriction-like endonucleolytic enzyme that first nicks DNA (to produce single-strand breaks) on strands of opposite polarity at symmetrically arranged nucleotide sequences (located at ends of genes or operons). This is followed by local denaturation of the region, promoted by a single-strand-specific DNA binding protein (i.e., an unwinding protein). Hydrogen-bounding between homologous DNA molecules can then be initiated and this allows for subsequent propagation of hybrid DNA in the pathway to formation of the synapton structure.


Induction of erythroid differentiation by dimethylsulfoxide in cells infected with Friend virus: relationship to the cell cycle. Cells infected with Friend virus can be induced to erythroid differentiation by culture with 2% dimethylsulfoxide. This study was designed to determine if dimethylsulfoxide causes the expression of erythroid differentiation by an effect on a particular phase of the cell division cycle. The infected cells were synchronized by exposure to 2 mM thymidine. It is shown that dimethylsulfoxide must be present during DNA synthesis (S-phase) and, possibly, shortly thereafter, to induce differentiation assayed by measuring hemoglobin synthesis. In order to achieve an effective intracellular incorporation of dimethylsulfoxide, cells must be exposed to the agent for at least 24-30 hr before the critical S phase. It is suggested that induction of erythroid differentiation in cells infected with Friend virus involves an effect of dimethylsulfoxide, or a metabolic product, that alters the program of transcription, during or immediately after DNA synthesis.


Steroidogenesis in rabbit preimplantation embryos. Rabbit preimplantation embryos were flushed from the reproductive tract at 24 hr (1- to 2-cell stage), 48 hr (morula), 72 hr (morula), 96 hr (blastocyst), 120 hr (blastocyst), and 144 hr (blastocyst) post coitum. At 168 hr (early postimplantation period), gestation sacs were excised, frozen, and sectioned in a cryostat. Delta5-3beta-Hydroxysteroid dehydrogenase [3(or 17)beta-hydroxysteroid:NAD(P) oxidoreductase, EC 1.1.1.51] activity was determined histochemically in whole preimplantation embryos and in sectioned postimplantation embryos. 3beta-Hydroxysteroid dehydrogenase activity began at 48 hr and was sustained through the late blastocyst stage (144 hr), with the exception of a brief drop, possibly cessation, of activity at 72 hr. There was no activity at 168 hr. Since 3 beta-hydroxysteroid dehydrogenase is a key enzyme in the metabolism of steroid hormones, its presence is strong evidence for steroidogenesis. Only 144-hr preimplantation embryos were used to determine 17 beta-hydroxysteroid dehydrogenase (estradiol-17beta:NAD 17-oxidoreductase, EC 1.1.1.62) activity, which was present, suggesting synthesis of estrogen. By means of radioimmunoassay, 144-hr preimplantation embryos were found to contain estradiol-17beta. Other authors have shown that rabbit blastocysts contain progesterone and other steroids, and these embryos can synthesize steroids from non-steroid and steroid precursors. Therefore, our results plus those of others prove that rabbit preimplantation embryos synthesize steroid hormones. Our present and previous results (with rats, hamsters, and mice) suggest that the steroid hormones synthesized by the embryo are critical for preimplantation embryogenesis and for implantation of the lbastocyst.


Ribonucleoprotein particles containing heterogeneous nuclear RNA in the cellular slime mold Dictyostelium discoideum. As in higher eukaryotes, heterogeneous nuclear RNA (HNRNA) in the cellular slime mold Dictyostelium discoideum is associated with proteins in the form of ribonucleoprotein particles. Mixing experiments with deproteinized hnRNA establish that the nuclear ribonucleoprotein particles are not formed artificially during isolation. In contrast to comparable material from mammalian cells (polydisperse, 40-25- S), Dictyostelium heterogeneous nuclear ribonucleoprotein particles sediment at only 55 S in sucrose gradients, possibly reflecting the smaller size of slime mold hnRNA relative to the large hnRNA found in higher eukaryotes. The RNA of the nuclear 55S ribonucleoprotein particles is shown to be hnRNA by virtue of its size (15S), content of polyadenylate sequences, and hybridization kinetics at DNA excess. The hnRNA-associated porteins are electrophoretically complex and have molecular weights between 20,000 and 150,000. In 0.35 M NaCl most of the proteins are released from the hnRNA. However, a single protein of 72,000-74,000 molecular weight remains bound, as indicated by its co-chromatography with the RNA on poly(U)-Sepharose and banding in Cs2SO4. The same protein is recovered when heterogeneous nuclear ribonucleoprotein is digested with T1 ribonuclease under conditions where the poly(A) is nuclease-resistant. The 73,000 molecular weight protein appears to be specifically bound to polyadenylate sequences in Dictyostelium hrRNA.


Cell-cell interactions: enhancement of glycosyl transferase ectoenzyme systems during Chlamydomonas gametic contact. Glycosyl transferase ectoenzyme systems that transfer galactose, glucose, N-acetylglucosamine, N-acetylneuraminic acid, mannose, and fucose have been detected on vegetative cells and gametes of Chlamydomonas moewusii. Gametes have higher levels of activity of the transferase ectoenzyme systems than morphologically identical vegetative cells, as determined by transfer of monosaccharide onto endogenous cell surface acceptors. When (plus) and (minus) gametes are mixed, there is a significant increase in the activity of transferase ectoenzyme systems. No enhancement in activity of transferase ectoenzyme systems occurs when (plus) and (minus) vegetative cells are mixed. Flagellar membrane vesicles obtained from (plus) and (minus) gametes show high activity of transferase ectoenzyme systems per mg of protein and also demonstrate enhanced activity upon mixing. Therefore, glycosyl transferases and acceptors seem to be located on the flagellar membrane and appear to have a function particularly related to gametic cells. The mechanism of cellular adhesion or recognition proposed by Roseman (1970, Chem. Phys. Lipids 5, 270-297), involving glycosyl transferases and acceptors, is strongly suggested by our data for the mating reaction in Chlamydomonas.


Distinct molecular structures of nuclear class I, II, and III DNA-dependent RNA polymerases. Class III RNA polymerases purified from the murine plasmacytoma MOPC 315 and from Xenopus laevis ovaries were compared. The subunit structures of the chromatographically distinct murine enzymes IIIA and IIIB were indistinguishable and were remarkably similar to that of the amphibian enzyme III. The plasmacytoma class III RNA polymerases were also compared with purified plasmacytoma RNA polymerases I and II. Sedimentation studies indicated that RNA polymerase III si significantly larger than RNA polymerase II, which is slightly larger than RNA polymerase I. Structural analyses showed that the molecular weights of the large subunits present in the class III enzymes (138,000 and 155,000) differ from those of the class II enzymes (140,000 and either 170,000, 205,000, or 240,000) and from those of the class I enzymes (117,000 and 195,000). Some low-molecular-weight subunits are also unique to each enzyme class. These results clearly distinguish the class I, II, and III enzymes on a structural basis. In addition, polypeptides of molecular weight 29,000 and 19,000 were found in all enzyme classes, a polypeptide of molecular weight 52,000 was found only in class I and III enzymes, and a polypeptide of molecular weight 41,000 was found only in class II and III enzymes. These findings are discussed in terms of the function and regulation of the RNA polymerases.


A general model for genetic recombination. A general model is proposed for genetic recombination. Its essential new feature is the hypothesis that recombination is initiated by a single-strand (or asymmetric) transfer, which may, after isomerization, become a two-strand (or symmetric) exchange. The likelihood of this transition from asymmetric to symmetric strand exchange determines certain characteristic features of recombination in any particular organism.


Reovirus messenger RNA contains a methylated, blocked 5'-terminal structure: m-7G(5')ppp(5')G-MpCp-. Reovirus mRNA synthesized in vitro by the virus-associated RNA polymerase in the presence of S-adenosylmethionine contains blocked, methylated 5'-termini with the structure, m-7G(5')ppp(5')G-MpCp. The functional significance and possible mechanism of formation of this novel 5'-5' terminal nucleotide linkage are discussed.


Short-lived messenger RNA in HeLa cells and its impace on the kinetics of accumulation of cytoplasmic polyadenylate. Accumulation of [3H]adenine in the acid-soluble pool and in nuclear and cytoplasmic poly(A) of HeLa cells shows that the nuclear poly(A) rises along a curve similar to that of the acid-soluble pool. By use of a [3H]guanosine pulse-chase experiment in adenine-grown cells, at least 35-50% of the pulse-labeled mRNA was found to have a half-life of about 1-2 hr. A mathematical model involving nuclear poly(A) synthesis and conservative transport to the cytoplasm has been derived from the new information about mRNA with a short half-life. This model predicts curves similar to those found for nuclear and cytoplasmic accumulation of poly(A). Thus, there is no necessity on kinetic grounds to invoke either nuclear turnover or cytoplasmic synthesis of poly(A).


Apocytochrome P-450: reconstitution of functional cytochrome with hemin in vitro. Synthesis of microsomal cytochrome P-450 in rat liver requires synthesis of apoprotein in rough endoplasmic reticulum and of heme in mitochondria. Dissociation of apoprotein and heme synthesis by concomitant treatment of rats with inducers of cytochrome P-450 (i.e., phenobarbital) and inhibitors of heme synthesis (i.e., cobalt) resulted in a relative excess of apocytochrome P-450. Under these circumstances, it was possible to reconstitute the holocytochrome by addition of hemin in vitro. The holocytochrome was detected spectrophotometrically by its CO-binding properties and functionally by its increased oxidative activity. Heme-mediated reconstitution was most efficient in cell fractions rich in mitochondria-rough endoplasmic reticulum complexes (640 times g fraction), suggesting that the structural association of these two organelles may represent a functional unit essential for the synthesis of holocytochrome P-450. These findings indicate that phenobarbital-mediated induction of apocytochrome P-450 is independent of heme synthesis. It is suggested that synthesis of the apocytochrome may be the primary and rate-limiting event in the formation of cytochrome P-450.


Dimethyl adipimidate: a new antisickling agent. A new approach to the prevention of sickling in vitro by use of the bifunctional crosslinking reagent, dimethyl adipimidate, is described. Prior treatment of sickle erythrocytes with dimethyl adipimidate will inhibit sickling in completely deoxygenated erythrocytes. Treated erythrocytes do not demonstrate the potassium loss and viscosity increase that usually accompany sickling. The oxygen affinity of hemoglobin in these cells is increased independently from changes in the concentration of 2,3-diphosphoglycerate. The hemoglobin obtained from treated erythrocytes contains a high-molecular-weight component as well as additional positively charged components. The relative degree to which chemical modification and/or crosslinking is an essential part of the antisickling properties of the material is not known.


Enhancement of soybean RNA polymerase I by auxin. When etiolated soybean seedlings are treated with the synthetic auxin, 2,4-dichlorophenoxy-acetic acid, cells of the mature hypocotyl become swollen and proliferate abnormally. This abnormal growth induced by auxin coincides with a 5- to 8-fold increase in the alpha-amanitin-insensitive RNA polymerase associated with isolated chromatin or nuclei. The alpha-amanitin-sensitive RNA polymerase activity of the auxin-treated hypocotyl was similar to that of control tissue. The increase in RNA polymerase I activity of chromatin and nuclei was maintained after solubilization and fractionation on DEAE-cellulose. Auxin thus appears to enhance RNA synthetic activity (i.e., ribosomal RNA) in mature soybean tissue by altering RNA polymerase I directly rather than by altering RNA polymerase I directly rather than by altering the chromatin template.


Sulfhydryl dependence in primary explant hematopoietic cells. Inhibition of growth in vitro with vitamin B12 compounds. Primary explants of P388, EL-4, and L1210 murine leukemia cells and of normal mouse bone marrow are shown to require sulfhydryl compounds for proliferation in vitro. Nine extablished cell lines show no stimulation by these compounds. Leukemia cells can lose the sulfhydryl dependence after various periods of adaptation to in vitro culture. Various sulfhydryl compounds have widely differing potencies in promoting in vitro proliferation of dependent cells. The effect appears to be specific for sulfhydryl groups in the reduced form. Vitamin B12 compounds inhibit the growth of sulfhydryl-requiring cells, apparently by catalyzing the oxidation of the sulfhydryl groups.


A general method for the introduction of enzymes, by means of immunoglobulin-coated liposomes, into lysosomes of deficient cells. Phagocytes of the smooth dogfish (Mustelus canis) contain no endogenous peroxidase within their lysosomes and constitute models for cells genetically deficient in lysosomal enzymes such as myeloperoxidase. We have obtained uptake of over 50% of exogenous horseradish peroxidase, provided the enzyme is exhibited to cells after incorporation into liposomes coated with heat-aggregated (62 degrees, 10 min), isologous IgM. Trapping of horseradish peroxidase (EC 1.11.1.7) by liposomes was established by chromatographic resolution (Sephadex G-200; Sepharose 2B and 4B) of free enzyme from that associated with liposomes; liposome-associated horseradish peroxidase, together with trapped markers of the aqueous compartment (glucose, CrO4 equals), were excluded, and free enzyme and markers were retained. Enzyme and marker trapping was not electrostatic, varied with the molar ratio of charged membrane components, and was reversed by detergent lysis (Triton X-100) of liposomes. Uptake at 30 degrees of aggregated IgM-coated liposomes containing trapped horseradish peroxidase exceeded that of free enzyme of 100-fold, and was more efficient than uptake of horseradish peroxidase presented in uncoated liposomes or in liposomes coated with native IgM. After phagocytosis, peroxidase-rich liposomes were localized exclusively in lysosomes of the phagocytes by ultrastructural histochemistry; the enzyme displayed over 50% latency to osmotic lysis. This method may prove to be of general use in the provision of exogenous enzymes to phagocytic cells genetically deficient in lysosomal hydrolases.


Studies on the primary structure of the influenza virus hemagglutinin. The amino-terminal sequence and composition of the subunits of the hemagglutinin (HA) of influenza virus has been determined. The hemagglutinin has been isolated by two techniques. (1) as the intact hemagglutinin after disruption of the virus in sodium dodecyl sulfate, giving 2 subunits of 58,000 daltons (HA1) and 26,000 daltons (HA2), and (2) after treatment of the virus with bromelain, giving 2 subunits of 58,000 daltons (BHA1) and 21,000 daltons (BHA2). In both preparations these subunits are linked by disulfide bonds. The aminoterminal sequences of HA1 and BHA1, and HA2 and BHA2 are the same. The composition of the 50 residue peptide associated with the membrane, which is removed from the C-terminus of HA2 by bromelain, is deduced and shown to be hydrophobic and contain 50% of the serine residues of HA2. The biosynthetic precursor of the hemagglutinin has been purified from the membranes of abortively infected chick fibroblasts and shown to have the same amino terminus as HA1. Thus the order of biosynthesis is NH2-HA1-HA2-COOH. The amino-terminal sequence of BHA2--at the cleavage site of the precursor--is shown to be a palindrome: NH2-Gly-Leu-Phe-Gly-Ala-Ile-Ala-Gly-Phe-Ile-. This sequence is conserved in representative viruses from each of the major pandemics. A region of homologous sequence is described between the hemagglutinins of influenza type A and B viruses.


Acute renal failure in McArdle's disease and myoglobinuric states. Reversible acute oliguric renal failure associated with skeletal muscle abnormalities due to either McArdle's disease or myoglobinuria developed in two patients. Renal angiographic and hemodynamic data revealed a preferential diffuse reduction in cortical perfusion. Arteriography showed absence of a cortical nephrogram and attenuation of the distal interlobar and arcuate arteries. Contrast medium was delayed in passage through the edematous kidney. These changes are distinct from those of chronic renal failure due to parenchymal disease. The renal arteriogram can be a useful adjunct in the differential diagnosis of acute renal failure of obscure origin.


Erythroleukemia following total-body irradiation for advanced lymphocytic lymphoma. A patient with advanced lymphocytic lymphoma received treatment with total-body irradiation. Two years later acute erythroleukemia developed which proved fatal. Previous experience with total-body irradiation is considered and the relationship between radiation exposure and leukemia discussed.


Cytochemical and cytogenetic findings in five human leukocyte long-term cultures (LAHL) of different origin. Five human leukocyte long-term suspension cultures were investigated by means of cytochemical and cytogenetic methods. A striking resemblance in the morphology of these cells originating either from peripheral blood or from spleen of patients with or without hematological disorders was found. Lymphocytic origin of all five cultures is suspected. In the three cultures a diploid karyotype was found with some aberrations. In one culture, derived from the spleen of a patient with panmyelopathy the mosaic 45 XX C -/46 XX was detected. Anomalies of C group chromosomes were the most consistent type of chromosome aberrations in two lines. Both were EBV positive.


Heritable cell cycle disturbances and late recovery in x-irradiated murine lymphoma L5178Y-S cell populations in vitro. 1. Ionizing radiation can induce in mammalian cells, besides the lethal effects, also heritable damages which retard cell cycle traverse for considerable humber of cell generationsl 2. Radiation-induced heritable lesions in murine leukaemic lymphoblasts L5178Y-S affect progesssion of the cells through the G2 phase of the cell cycle. 3. Late recovery of proliferative activity which must be connected with elimination of the G2 block is a common phenomenon in the heritably damaged L5178Y-S sublines derived from single cells. 4. A possibility should be taken into consideration of employing the cells heritably damaged by radiation as convenient models for studies on some disturbances which accompany ageing of the mammalian cells. 5. It seems that results of studies on both the cells heritably damaged by radiation and the ageing cells could be useful for evaluation of possibilities of prevention, control or elimination of the heritable cell cycle disturbances.


Ribonucleases in mouse ascitic tumor cells during ageing in vivo and in vitro. Ribonuclease activities have been determined in cell extracts of mouse L5178Y lymphoma grown in vivo and in vitro. From the obtained results it follows that the level of studied enzymes changes in both systems during ageing of the cells. Moreover, when lymphoma cells are cultured in vitro a marked decrease in specific activity of alkaline ribonuclease II is observed.


Proliferation and morphology of ascitic cells as a function of age in cell culture. Ascitic cells in the logarithmic growth phase increase the accumulation of glycogen particles in the course of explantation into suspension culture, probably due to the increasing arrest of glycogenolytic enzymes. At this age, a part of the cells are capable of restitution by exopinocytosis of the glycogen-containing vacuoles ia formation of cytoplasmic buds. Older cells, taken from the plateau-phase, pass atypical differentiation and ageing, are less capable of hindering the abnormal accumulation of glycogen and the hypervacuolisation. As a consequence, the cells finally degenerate and die.


Ultrastructure of the sinus wall of murine bone marrow in myelogenous leukemia. The ultrastructure of bone marrow of RF mice having an acute myelogenous leukemia induced by inoculation with leukemic cells was investigated. In several respects sinuses of leukemic marrow are similar to normal marrow. Sinuses are present in numbers approximating that of the normal; the lining cells of the sinus wall have organelles similar in distribution and number to those of normal lining cells; the sinus wall is continuous, having openings only in conjunction with blood cells that are migrating through it (migration pores); migration pores occur within and not between lining cells. Abnormalities observed in leukemic marrow are the occurrence of virus-like particles in leukemic cells, the presence of numerous particles 300 to 500 A in diameter in the extracellular space, reduction in the number of adventitial cells of the sinus wall and an increase in the thickness and distribution of extracellular material located near the basal surface of lining cells.


Excess leukemia in cohorts of children born following influenza epidemics. Two series of data from the California State Department of Health and one from Children's Hospital of Los Angeles were analyzed to determine whether an association exists between influenza epidemics and incidence of leukemia in children born following such outbreaks. Of leukemic children born in areas for which information on past influenza activity was available, the population-based Alameda County Cancer Registry recorded 89 cases during 1960-1969, the California Tumor Registry recorded 653 cases during 1950-1970, and Children's Hospital recorded 575 cases during 1957-1972. Flu epidemics were identified and flu cohorts constructed such that leukemic children who could have been in utero during a flu epidemic constituted a flu cohort. Based on the total number of leukemia cases reported and the proportion of at-risk weeks contributed by the flu cohort, expected numbers of leukemia cases from the flu cohort were computed for each age. In each series, there was an excess of leukemia cases in the flu cohort, contributed primarily by the 0-4 age group. Trimester analysis indicated that the greatest excess occurred in children who were in the first trimester of gestation during a flu epidemic. Incidence data from the Cancer Incidence System of the San Francisco Bay Area Resource for Cancer Epidemiology and the Third National Cancer Survey show a relative risk of 3.4 for this group. Due to sources of misclassification in this study, such as analysis of flu cohorts rather than individuals whose mothers actually had influenza during pregnancy, the results tend to be diluted. If influenza is a causative factor, the actual increase in leukemia risk is likely to be much greater than this analysis indicates.


Platelet function in patients with high platelet counts. Platelet function tests were done to ascertain whether they might have discriminatory significance in the differentiation of a myeloproliferative disorder from secondary thrombocytosis in a patient with an elevated platelet count. Amongst 14 subjects with polycythaemia vera and essential thrombocythaemia, significant abnormalities of platelet aggregation were the rule, while defective aggregation was unusual in 16 subjects with secondary thrombocytosis. Measurements of the bleeding time and of platelet factor 3 activity were of some value, but significant overlap was noted. Platelet function in four of five subjects with chronic myeloid leukaemia was essentially normal.


Some properties of neurophysins isolated from bovine neurosecretory granules. Our experiments with the neurophysin-related proteins from bovine NSG have demonstrated that these species differ in several important respects from the materials conventionally prepared. (1) In structural terms, the NSG proteins are essentially identical with the conventional neurophysins in amino acid composition and closely similar in immunoreactivity; however, the presence of carbodydrate and lipid moieties in the NSG material, no matter how they are attached, constitutes a structural difference apparently sufficient to cause considerable changes in properties. (2) The affinities for the neurohypophyseal hormones of the NSG proteins are very much higher than those of the "conventional" neurophysins and, moreover, the binding properties of the NSG material are much more stable with time under the conditions of the binding experiments. (3) The low binding capacities of the NSG materials, even when they are purified to apparent molecular homogeneity, indicate a functional heterogeneity perhaps related to supramolecular structure. (4) The conversion of the NSG proteins by acid or alkali treatment to materials resembling the "conventional" neurophysins in their binding properties suggests that the latter may be isolation artifacts. Although we cannot as yet consistently explain the properties of our neurophysins from NSG, we offer the hypothesis that the low binding capacity, as also the Hill coefficient greater than 1 (cf. Reference 25) are indicative of molecular aggregation, perhaps mediated or facilitated by the nonprotein components. It is conceivable that such aggregation, proceeding in the more "natural" environment of the NSG in a more precisely organized manner, might constitute the truly "native," fully functional state of the neurophysins. In this context it is of interest to record our preliminary observations, which suggest the presence of a protein of 10,000 mol. wt. in the NSG membrane fraction (SDS gel) as well as electron-microscopic indications30 of a highly organized ("crystalline") structure within these membranes. Although, therefore, the materials we have described may not merit the description of "native" neurophysins, we believe that they are certainly closer to the native state than the proteins conventionally isolated; and we would suggest that any discussion of the biological role of the neurophysins based on the properties of the conventional preparations may be at best speculative, and at worst misleading.


Observations on the lipolytic and melanotropic properties of neurophysin proteins. Previous work indicated that brain contains 3 types of lipolytic-melanotropic peptide: (1) in adenohypophysis: ACTH, alpha-MSH, beta-MSH, peptide I, peptide L', beta-lipotropin and gamma-lipotropin; (2) in neurohypophysis: peptide 7D6, also termed neurophysin I, peptide II or Wuu-Saffran peptide; (3) in extrahypophyseal regions: peptide IIF. Bovine and human neurophysin I prepared by R. Walter has now been found devoid of lipolytic and melanotropic activities. Porcine and bovine peptide 7D6, closely similar or identical to bovine neurophysin I in electrophoretic mobility and amino acid composition, were therefore reexamined to determine whether their lipolytic-melanotropic property resided in a contaminating factor. When peptide 7D6 was analyzed in 100 transfer counter current distribution (1 butanol/0.1M NH4 HCO3), the neurophysin was recovered in tubes 1-9 (7D6-alpha) representing 95% of 7D6. 7D6-alpha was inactive in lipolytic and melanotropic assays. The biologic activities of 7D6 were recovered instead in tubes 50-70 (labeled 7D6-beta), representing 5% of 7D6. 7D6-beta proved to be a peptide with MW 1000-3000, closely similar to peptide IIF in amino acid composition, MW, and Rf values in 4 systems of paper chromatography.


Environmental health hazards from high-powered, infrared, laser devices. The potential health hazards associated with high-power laser systems are not limited to the direct beam. In addition to the obvious hazards of direct beam exposure of personnel, environmental problems may arise from electrically-energized equipment, excessive noise from the laser itself, and from hazardous fumes, gases, and vapors originating from components of the laser or from the target material.


Dibromomannitol in the treatment of chronic granulocytic leukemia: a prospective randomized comparison with busulfan. Dibromomannitol (DBM) is a new agent for the treatment of chronic granulocytic leukemia. A propsective evaluation of the drug was undertaken in a randomized comparison with busulfan. Forty previously untreated, Philadelphia chromosome-positive cases were treated, with 20 patients in each treatment group. The protocol provided for continuous maintenance therapy after remission induction, with a crossover to the opposite drug in patients who became refractory to the primary agent but are without evidence of blastic tranformation. There were 14 remissions in the DBM group and 15 in those treated with busulfan. The rate of decrease of the elevated leukocyte count was more rapid with DBM, but prolonged disease control off treatment occurred in only three of 14 cases as opposed to nine of fifteen busulfan-treated patients who required a median delay of 12 mo before maintenance could be initiated. Hypoplasia occurred in one DBM patient and two busulfan cases. Following recovery, crossover to the opposite drug in two cases again resulted in hypopllasia. Increased skin pigmentation, amenorrhea, pulmonary fibrosis, and cytologic dysplasia, commonly associated with busulfan adminstration, were also noted with DBM. The median duration of disease control with busulfan was 34 mo and 26 mo with DBM. There was no signigicant difference in the incidence of blastic transformation, and median survival for both groups was 44 mo. DBM appears to be as effective as busulfan in the treatment of the chronic phase of CGL but with a more predictable myelosuppressive action. The principal advantage of busulfan over DBM is the fact that more than half the busulfan-treated patients experienced prolonged disease control off treatment.


Measurement of vitamin B12-binding proteins of plasma. II. Interpretation of patterns in disease. The technique described in the preceding paper was applied to 12 abnormal sera selected for their increase in one or more B12-binding proteins. Even in the presence of large amounts of R-type binder, the ammonium sulfate technique gave a reliable separation of R binding proteins from TC II. Measurement of the TC II in abnormal sera gave results identical to those obtained by the more standard gel filtration. The R binders of four subjects with myeloproliferative disease were further separated into alpha2-R and alpha1-R. The pattern  of B12 binding of polycythemia vera (PV) was an exaggeration of the normal pattern. Binding to alpha2-R was three to four times that to alpha1-R, although the total amounts bound to both were increased. In chronic myelogenous leukemia (CML), both alpha2-R and alpha1-R were also increased, but in contrast to binding in normal sera, alpha1-R predominated.  In order to interpret the findings, either whole serum R or alpha1-R and alpha2-R from patients with myeloproliferative disease were subject to isoelectric focusing. Alpha2-R consisted pricipally of components isoelectric at pH 2.9, 3.0, and 3.1. These components were present in only minor amounts in normal serum and were somewhat increased in the serum of PV. These components were very much increased in the serum of CML and predominated. Alpha2-R consisted of those components isoelectric at pH 3.4,3.6, and 4.0. These components predominated in the unsaturated binding capacity of normal sera and that of PV. It was concluded that the division of plasma R binders into alpha1-R and alpha1-R by the technique described provided information useful in the study of myeloproliferative diseases.


Isoleucine metabolism by leukemic and normal human leukocytes in relation to cell maturity and type. The metabolism of an essential amino acid, isoleucine, by human leukemic and gradient-separated normal human leukocytes of various types and maturity was studied. Blood leukocytes were isolated and incubated with (U-14C) isoleucine. Separation of metabolic intermediates was accomplished by sequential extraction. The rate of isoleucine incorporation into protein by immature cells from untreated patients with acute leukemia (15.9 plus or minus 2.4 nmoles/hr per 10-8 leukocytes) was considerably higher than the rates of incorporation by mature neutrophils (3.2 plus or minus 0.5 nmoles/hr per 10-8 leukocytes), lymphocytes (7.7 plus or minus 1.2 nmoles/hr per 10-8 leukocytes), and eosinophils (6.2 plus or minus 1.3 nmoles/hr per 10-8 leukocytes). Those cell preparations with more blast cells had higher rates of protein synthesis. In addition, those cells with greater thymidine incorporation had higher rates of protein synthesis. The leukocytes both oxidized isoleucine and incorporated it into cell isoleucine and incorporated it into cell lipid. The rates of these metabolic processes were characteristic for various types and maturity of leukocytes. This study demonstrates a relationship of rate of protein synthesis to leukocyte immaturity. This relationship is maintained in neoplastic leukocytes. It suggests that the requirement of the mitotic process for newly synthesized protein is greater than that for the elaboration of the protein products of the mature leukocyte.


De novo appearance of the ph-1 chromosome in a previously monosomic bone marrow (45,XX,-6): conversion of a myeloproliferative disorder to acute myelogenous leukemia. Bone marrow examination of a patient with a myeloproliferative disorder revealed monosomy for chromosome No. 6 (45,XX,-6). Two months later, during blastic crisis, reinvestigation of the bone marrow showed the presence of the Ph-1 chromosome in the previously aneuploid cell line (45,XX,-6,-22,+Ph-1). This case differs from those previously published in that the Ph-1 chromosome appeared de novo during the development of frank acute myelogenous leukemia.


Occurrence of hepatitis and hepatitis B surface antigen in adult patients with acute leukemia. Fifty-eight adult patients with acute leukemia were screened at the onset of the disease for hepatitis B antigen (HBSAg) in the serum, and during the course of the disease for the development of hepatitis B. One patient had a positive test for HBSAg by the radioimmunoassay technique only at the time leukemia was diagnosed; this patient had received transfusions some years before. In six patients icteric hepatitis B developed; five recovered completely and one died of leukemia during the course of hepatitis. All patients in whom hepatitis developed had received transfusions as a part of supportive therapy for leukemia. The hepatitis risk for patients who received transfusions of blood found to be negative for HBSAg by counterimmunoelectrophoresis was 0.26 percent per unit of blood administered.


Primary granulocytic sarcoma of the small bowel. A young man developed obstruction of the small bowel due to a neoplastic process, which in retrospect proved to be a primary granulocytic sarcoma, preceding acute granulocytic leukemia for more than 3 years. The histologic, histochemical and ultrastructural findings are presented, together with a review of the literature on granulocytic sarcomas, particularly those presenting as aleukemic forms. It is suggested that these forms may not be so rare and that careful search, using currently available methods, will be rewarding.