Familial enteropathy: a syndrome of protracted diarrhea from birth, failure to thrive, and hypoplastic villus atrophy. We have studied 5 infants with persistent severe diarrhea from birth and marked abnormalities of absorption associated with failure to thrive leading to death in 4 infants. Three had siblings who died and a sibling of a 4th is ill at present, all with a similar illness; 2 were the products of consanguinous marriages. Exhaustive investigation failed to identify a recognized disease entity in any patient. Steatorrhea, sugar malabsorption, dehydration, and acidosis were severe in all patients, whatever the diet fed. Total parenteral nutrition was used, but excessive stool water and electrolyte losses persisted even when nothing was fed by mouth. There was no evidence of a hematological or consistent immunological defect in any infant and no abnormalities of intestinal hormones were noted. In the duodenal mucosa of all infants we saw similar abnormalities characterized by villus atrophy, crypt hypoplasia without an increase in mitoses or inflammatory cell infiltrate in the lamina propria and in villus enterocytes absence of a brush border, increase in lysosome-like inclusions, and autophagocytosis. In 3 infants studied by marker perfusion of the proximal jejunum we found abnormal glucose absorption and a blunted response of Na+ absorption to actively transported nonelectrolytes; in 2 there was net secretion of Na+ and H2O in the basal state. Our patients evidently suffered from a congenital enteropathy which caused profound defects in their capacity to assimilate nutrients. The similar structural lesion seen in the small intestinal epithelium of all of our cases undoubtedly contributed to their compromised intestinal function, but the pathogenesis of this disorder, if indeed it is a single disease, remains obscure.


Intestinal disaccharidase activities in relation to age, race, and mucosal damage. Studies were undertaken to determine the relationship of intestinal disaccharidase activity to age and race, and the relationship of mucosal damage to a primary low lactase activity. The first study consisted of data on 399 persons (339 whites, 53 blacks, and 7 American Indians) ages 1 month to 93 years, with normal intestinal histology. Among whites, all 117 children 5 years old or under had high lactase levels, whereas low levels were found only in subjects over 5 years of age. No low lactase levels were identified among the 11 black children 3 years old or under, but in comparison to coetaneous white children, their mean lactase activity was signficantly less. The majority of older blacks had low lactases. In whites and blacks alpha-disaccharidases did not participate in the age-related changes demonstrated with lactase. Of the 7 American Indians, none under 26 months old had low lactase levels, whereas the 4 over 10 years old had low activities. Heterozygotes for sucrase-isomaltase deficiency were identified only among whites. Low lactase levels developed during childhood in all races studied, however, many for unknown reasons maintained their lactose tolerance until adulthood. In the second study of 13 additional children with secondary disaccharidase deficiencies, emergence of a primary low lactase was related to age and race, rather than to mucosal damage. It appears that primary low intestinal lactase levels are absent or rare in whites under 5 and blacks under 3 years of age, and the deficiency is not related to mucosal damage.


The alcohol dehydrogenase polymorphism in populations of Drosophila melanogaster. I. Selection in different environments. The allozyme polymorphism at the alcohol dehydrogenase locus in Drosophila melanogaster was studied in order to obtain experimental evidence about the maintenance of this polymorphism. Populations started with different initial allele frequencies from homozygous F and S lines showed a convergence of frequencies on regular food at 25 degrees, leading to values equal to those in the base populations. These results were interpreted as due to some kind of balancing selection. In populations kept at 29.8 degrees, a lower equilibrium F frequency was attained. Addition of ethanol and some other alcohols to the food gave a rapid increase in F frequency, and high humidity decreased the F frequency slightly. Combination or alternation of ethanol and high humidity had variable effects in the populations tested. For a further analysis of the allele-frequency changes, estimates were obtained for egg-to-adult survival under different conditions and for adult survival on ethanol-supplemented food. On ethanol food (both at regular and high humidity), egg-to-adult survival of SS homozygotes was considerably lower than that of the FF and FS genotypes. Under regular conditions of food, temperature and humidity, a tendency to heterozygote superiority was observed, while at high humidity a relative high survival of SS was noticed in some tests. Adult survival of SS was lower than that of FF, but FS was generally intermediate, though the degree of dominance differed between populations. The results are consistent with the hypothesis of the occurrence of selection at the Adh locus.


Mitotic recombination in the heterochromatin of the sex chromosomes of Drosophila melanogaster. The frequency of spontaneous and X-ray-induced mitotic recombination involving the Y chromosome has been studied in individuals with a marked Y chromosome arm and different XY compound chromosomes. The genotypes used include X chromosomes with different amounts of X heterochromatin and either or both arms of the Y chromosome attached to either side of the centromere. Individuals with two Y chromosomes have also been studied. The results show that the bulk of mitotic recombination takes place between homologous regions.


[UV-mutagenesis in Bacillus subtilis. VII. Mutability of recA, recB and recF strains]. UV-light induces reversions to threonine-independence in BD170 Rec+ cells, and does not induce them in isogenic strain BD241 recF. Reversions to methionine-independence are induced in cells GSY1028 recB, and are not in isogenic strain GSY1025 recA. It is possible to construct, with the use of transformation, a viable strain carrying mutations recF and su, the latter imparts threinine-independence to cells. Hence, the absence of UV-induced reversions in recF (and probably in recA) cells can not be explained by the lethal effect of joining, in one genome, two mutations each of which decreases a viability of bacteria. Formation of UV-induced forward mutations which provide additional growth requirements to bacteria is not disturbed in strains recA and recF. Experimental data allow to conclude that UV-induced mutagenesis is not a function of any of two known mechanisms of recombination which function in Bacillus subtilis cells.


Functional half-life of the exocellular protease mRNA of Bacillus megaterium. Functional half-life of the exocellular protease mRNA was determined in in exponentially growing and stationary cells of the asporogenic strain of Bacillus megaterium KM and in the sporogenic strain of B. megaterium 27 during sporulation. No reserve of the protease mRNA could be detected in the cells and the half-lives were determined to be 6--7 min in the exponential and stationary cells of B. megaterium KM and 7.5--8.5 min in B. megaterium 27. The mean half-life of mRNA for cell proteins was determined to be 3.5--4.5 min. Thus, as compared with the mean half-life of mRNA for cell proteins that of mRNA for the exocellular protease is slightly longer.


Isolation of glucosyltransferase from Streptomyces aureofaciens. Streptomyces aureofaciens B 96 grown on a synthetic medium glucosylated exogenous 1,2-dihydroxy-9,10-anthraquinone (alizarin). The glucosylation was inhibited by 2,4-dinitrophenol added to the cultivation medium. A cell-free preparation was obtained from the mycelium isolated after 16 h of growth and was found to catalyze the transfer of glucose from glucosyluridyl diphosphate to 1,2-dihydroxy-9,10-anthraquinone, giving rise to 1-hydroxy-2-(beta-D-glucopyranosyloxy)-9,10-anthraquinone.


alpha-Mannosidases of genera Aspergillus and Rhizopus. Activity and capacity to utilize Saccharomyces cerevisiae mannan of the best alpha-mannosidase producer Aspergillus flavus Link 69. Strains of fungi imperfecti of genera Aspergillus and Rhizopus were tested for the ability to produce alpha-mannosidases. The most suitable alpha-mannosidase producer of a total of 20 strains under study was Aspergillus Ravus Link 69. The parameters studied during the cultivation included the growth rate expressed as cell dry weight, alpha-mannosidase activity of the extracellular medium with p-nitorphenyl alpha-D-mannopyranoside as substrate, and utilization of Saccharomyces cerebisiae mannan via its disappearance from the cultivation medium.


Can the United States learn from foreign medical insurance systems? After data are given on trends in health care expenditures in several nations, selected health care cost indicators in Canada and in the United States are contrasted in more detail; and a study of the Canadian health care insurance system is criticized. Finally some broader questions on the nature of U.S. social policy are raised.


Chromosomal investigations in children with pyknolepsy on dipropylacetate monotherapy. We analyzed chromosome preparations obtained from leukocytes of ten children with pyknolepsy and treated with dipropylacetate (DPA) as monotherapy. Structural or numerical aberrations were not found more frequently in our patients than in five normal children (control group).


[The present situation of antibacterial resistance (author's transl)]. The various types of bacterial resistance (natural species resistance, chromosomal and plasmidic resistance) and their mechanisms are described. Thereafter, a survey on the resistance is given using investigations from different sources. The distribution of resistant strains dependent on the geographical location and the situation of the patients (ambulatory--hospitalized) is described, and the development of resistant strains in dependance of time is analyzed. Finally, the phenomena of resistance against aminoglycoside and beta-lactam antibiotics are explained in more detail.


Biosynthesis and assembly of IgM free thiol groups present on cytoplasmic and membrane associated IgM. The free thiol groups present on various intracellular precursors of polymeric IgM have been studied in two mouse tumours; McPC 1748 which resembles a 10-25h LPS-stimulated lymphocyte with surface IgM, and Y5781 which resembles a 80-110h LPS stimulated lymphocyte with no surface IgM and a large pool of intracellular 19S IgM. The intracellular IgMs* of both cell lines possesses four free thiol groups per molecule, two of which are probably involved in linking the subunits during polymerisation. In conjunction with earlier reports this shows that independent IgM-synthesizing tumours with widely differing characteristics contain IgMs with four free thiol groups, indicating that this is the major precursor form preceding polymerisation. Although the secreted 19S IgM had no detectable free thiol groups, some of the H chains of the intracellular 19S IgM of Y5781 had at least one which may be involved in J chain binding. The IgMs of slow turnover associated with McPC 1748 cells was shown to be exposed on the cell surface and was identical with the cytoplasmic IgMs in pI and number of free thiol groups. These thiol groups become blocked before release into the medium.


Human triclonal anti-IgG gammopathy. I. Iso-electric focusing characteristics of the IgG, IgA and IgM anti-IgG and their heavy and light chains. Human IgG, IgA and IgM anti-IgG autoantibodies have been isolated from the serum of an individual with Felty's syndrome. These were initially noted as soluble circulating serum complexes by analytical ultracentrifugation. Isolation was accomplished by solid phase immunoadsorption and each of the three antibody populations obtained was shown to be of restricted heterogeneity by liquid and polyacrylamide gel electrofocussing methods. Type kappa light chains were obtained from each protein. Co-isoelectric focusing experiments of all possible pairs of these light chains showed them to have identical net charge characteristics. Heavy chains obtained from each protein were also monoclonal and of differing isoelectric point. The availability of this serum provides a human model with which to study the changes which may occur in autoantibodies during the autoimmune response.


Marmoset species variation in the humoral antibody response: in vivo and in vitro studies. A comparison of the in vivo and in vitro antibody response capabilities of two marmoset species, Saguinus fuscicollis and Saguinus oedipus oedipus, revealed the former to be superior in elaborating humoral antibody. In vivo challenges with Escherichia coli lipopolysaccharide (LPS) and Salmonella typhi flagella consistently yielded higher antibody titres in S. fuscicollis; indeed, with LPS antigen, multiple inoculations of S.o. oedipus marmosets led ultimately to a decrease in antibody formation, in contrast to the anamnestic response of S. fuscicollis. This species differential in immune competence was also suggested in the in vitro stimulation of peripheral blood leucocytes (PBL) and spleen cells with sheep red blood cells (RBC). None of 55 S.o. oedipus PBL cultures and 49 of 89 (55%) S. fuscicollis cultures responded to the test antigen. A similar differential in response to sheep RBC was noted with the spleen cells of each species, although this report contrasts the antibody-forming potential of two marmoset species, a comparison of the immunological response profile of marmosets to those of other laboratory animals challenged with similar antigens suggests these primates may be relatively incompetent. The possible relationship between the haemopoietic chimerism of marmosets and a diminished immune competence is discussed.


Reaction of 7,12-dimethylbenz(a)anthracene with DNA of fetal and maternal rat tissues in vivo. Pregnant BD-IX rats (21st day of gestation) received a single IV injection (15 mg/kg) of tritiated 7,12-dimethylbenz(a)anthracene (DMBA), A DOSE KNOWN TO INduce a high incidence of nervous-system tumors in the offspring. The animals were killed 12 h later and hydrocarbon-deoxyribonucleoside products from DNA of maternal and fetal tissues were separated on Sephadex LH-20 columns eluted with a 20-100% methanol gradient. Concentrations of the major DMBA-DNA adduct varied considerably, with highest values in maternal intestine, liverand lung, followed by spleen, kidney and brain. In fetal intestine and liver, concentrations were 34% and 16% lower than in the respective maternal organs whereas the reaction with cerebral DNA was 2 1/2 times higher in fetuses than in the pregnant mother. This indicates that there is no significant placental barrier to DMBA or DMBA metabolites involved in DNA binding and that rat fetuses participate in the metabolic formation of the ultimate carcinogen.


Chromosome changes (trisomy 15) in murine T-cell leukemia induced by 1,12-dimethylbenz(a)anthracene (DMBA). The banding pattern of DMBA-induced leukemias in C57BL/6 mice revealed a very constant chromosome pattern: the presence of trisomy 15 in almost all leukemic cells. This finding strongly suggests that chromosome 15 trisomy is the first detectable specific chromosome change associated with the development of DMBA-induced T-cell lymphomas. A similar association was previously shown with regard to development of radiation-leukemia-virus-induced T-cell lymphoma. It is conceivable that in tumors of diverse etiologies common cytogenetic changes may appear in the same common target-cell precursor, by a process of the "convergent microevolution" type.


The effect of sublingually administered nitroglycerin on the contraction of the human gallbladder. Nitroglycerin (0.5 mg) was administered sublingually either before (n = 10) or after (n = 10) a standard contraction meal (200 ml of cream) during oral cholecystography. In both groups the standard contraction meal caused a significant contraction of the gallbladder. Nitroglycerin had no significant dilatation effect; hence its benefit during an acute attack of pain in a patient with gallstones seems to be questionable.


Significance of the orbital floor in zygomatic injuries. Fifty years after the publication of Harold Gillies' work, an assessment of zygomatic injuries is made, in the light of a half century of medical advances. Recent experience suggests that the fractured orbital floor is the commonest and most significant component of all zygomatic injuries. Exploration of 582 floors in the last 5 years revealed that over 20% had true blowout fractures, without damage to the orbital rim. A further 5% had torn periosteum with only minimal bony damage. Only two cases (0.3%) had fractures of the rim without a blown-out floor. The significance of floor damage is considered. This is usually more severe than expected. Even minimal damage--torn periosteum alone--may be followed by severe late sequelae, out of proportion to the magnitude of the apparent injury. If such sequelae develop late, their relationship to the injury is not suspected. The related soft tissues are very vulnerable. Vigorous manipulation of the malar (or maxilla in LeFort II injuries) does as much damage to them, as did the original trauma. Our therapy should be designed to protect these tissues during necessary manipulation.


Some missile injuries due to civil unrest in Northern Ireland. Some missile injuries are reviewed after nearly 8 years of continuous warfare. A feature of many of these injuries is the early admission to hospital which has had a profound effect on the survival rate and the recovery period. Some examples are given of injuries inflicted by rubber bullets. The effects of wounding by low and high velocity missiles are described and examples given. An injury caused by a missile incorporated in a bomb is also shown.


Internal fixation of fractures.

Internal fixation of fractures. In recent years close consideration of the biomechanical principles of treatment of mandibular fractures has led to the use of operative as well as conservative methods. Since this combined method of treatment appeared cumbersome, a new kind of osteosynthesis plate was developed for functionally stable internal fixation of mandibular fractures, without the necessity of additional fixation elements. After consideration of the biomechanics of the mandible, an even greater indication for the use of the lag-screw osteosynthesis is found. Use of both the tension band plate and the lag screw makes it possible to perform the operation intraorally. This is a further indication for the use of the operative internal fixation of fractures in the treatment of mandibular fractures, since it has many advantages for the patient.


Treatment of fractures of the articular process by functional stable osteosynthesis using miniaturized dynamic compression plates. The application of miniplates in fractures of the base of the articular process, developed by Schilli for orbital stabilization of malar bone impression fractures, is reported. The ends of the fragments after open reposition and reduction of the proximal fragment could be fixed durably by functional stable compression osteosynthesis in 35 patients with fractures and luxation or dislocation. In spite of the technical difficulties in performing this operative method the procedure should find a large application because of the optimum anatomic and functional results.


Combined surgical and orthodontic management of the oral abnormalities in children with cleidocranial dysplasia. Children with cleidocranial dysplasia have dental abnormalities which combine to prevent normal tooth eruption, and which if untreated may result in abnormal facial and jaw growth. A technique combining orthodontics and oral surgery has resulted in the establishment of excellent occlusion and facial appearance in these patients. Recent advances in direct enamel bonding techniques for orthondontic attachments have permitted a conservative surgical approach with minimal bone removal during surgery to expose unerupted teeth prior to orthodontic treatment.


Surgical-orthodontic approach to skeletal class III malocclusion. Analysis of 45 cases with evaluation of curved oblique osteotomy and sliding osteotomy. A curved oblique osteotomy in which the ascending ramus was cut obliquely on a curved line from its anterior border to the angle was used for the treatment of 29 patients with skeletal Class III malocclusion, and 16 other patients were corrected by either an ordinary body ostectomy or a sliding osteotomy in the first premolar region. Both curved oblique osteotomy and sliding osteotomy could easily be performed with a Stryker's reciprocating saw, and osseous healing at the sites of surgery was rapid as a large area of intimate bony contact between the segments was obtained. The resulting profile and skeletal changes studied by cephalograms were excellent, with no significant relapse, and recovery of a stable occlusion was attained. The combined approach with orthodontists which included thorough analysis of each patient, preoperative alignment of the dental arches and postoperative care was essential for obtaining the best results.


Follow-up investigations on operated cleft palates. Follow-up investigations were made on 98 uni- and bilateral cleft lip and palate patients referred to an orthodonitc therapy. As the patients have been operated by various methods and by different surgeons, the question arose as to whether the timing of the operation still influences the development of the dentition. Early operated patients (uranoplasty) exhibited more often impaired maxillary growth than late operated patients. Orthodontic interventions proved especially successful when applied early and when they were not hindered by cicatrical contractions.


Tumors of the head and neck. A 4-year study of a multidisciplinary approach. A multidisciplinary conference composed of the essential medical, surgical, dental, and allied specialists involved in the region of the head and neck, with resources to call upon other contributors when necessary, was undertaken at a major teaching center in the Northeastern U.S.A. (Long Island Jewish Hillside Medical Center). Meeting on a bimonthly basis with referrals accepted from all sources, but non-publicized, a total of 343 patients were seen over a period of 50 months. The results indicate that optimum patient care can be achieved with a minimum loss of time for treatment initiation and substantial cost savings from these specialists meeting as a group.


Odontological section of a bone tumour registry. A Bone Tumour Registry is incomplete without the inclusion of the odontogenic tumours. The odontogenic tumours originate in only three bones of the body so there is a case for the establishment of a separate section in a Bone Tumour Registry for their consideration. Problems of classification and differential diagnosis are different from other bone tumours. The clinicians and diagnostic specialists concerned with their recognition and treatment often only work in the oral field. They need the association with their colleagues working in the general bone tumour field which a Bone Tumour Registry can provide. In an area with a small population, the variety and number of cases seen will be small; establishment of a Bone Tumour Registry is a useful educational tool. The setting up of a Bone Tumour Registry at an early stage of the development of an area means that the lines of communication and collection of cases for the Registry can be more easily organized than in more populated areas. The Bone Tumour Registry in Perth and the setting up of its odontological section are described in this paper.


Central neurilemmoma of the jaws. Review of literature and case report. Neurilemmomas presenting as primary central bone tumors are extremely rare. Only 21 cases have been reported to have arisen in the jaws; all except for one have occurred in the mandible. The majority of these have been associated with the inferior dental nerve. A case of a central neurilemmoma arising in the anterior mandible is reported. Its probable origin is from one of the alveolar branches of the incisive nerve--an unusual site in the mandible. The radiographic features include expansion of cortical bone, resorption of roots of teeth, the presence of lace-like bony septa and a spotty calcification within the tumor. The treatment and the prognosis are briefly discussed.


Ameloblastomas.

Ameloblastomas. Ameloblastomas are slow-growing, destuctive lesions of the jaws. They have a wide age distribution and occur in both sexes. In considering the treatment of these lesions, one must take into consideration the patient's age, the patient's concern for his (her) functional, social and aesthetic requirements. It is not unreasonable to aim at a conservative approach first, then radical surgery when the lesion recurs. Small lesions can be treated by local block excision or curettage. For large lesions and recurrences in the mandible, jaw resection and immediate bone graft is indicated. In the author's experience, split iliac crest graft gives the best clinical result.


Indication and appreciation of operative procedures for mandibular ankylosis. Mandibular ankylosis may be of various etiology. A number of operative procdures have been presented and criticized, but the most appropriate procedure for ankylosis is not universally accepted. During the past decade, 17 cases of mandibular ankylosis have been treated surgically in the Nagoya University Hospital. The etiology includes both temporomandibular ankylosis and extraarticular origin. Three different surgical procedures were used: (1) High operation, in which skin incision is made in the preauricular region. This method is applied for moderate arthrogenic cases. (2) Low operation, in which skin incision is made in the submandibular region. This is applied for severe arthrogic cases and extraarticular ossification cases. (3) Tubed pedicle skin grafting is applied for buccal contracture cases caused by noma etc. A long-term follow-up to 10 years has disclosed many interesting findings and made it possible to evaluate each operative procedure.


Role of the meniscus in the etiology of posttraumatic temporomandibular joint ankylosis. From an analysis of the factors that could contribute to the development of post-traumatic TMJ ankylosis, it is evident that a number of different conditions are probably operant. Based on clinical and experimental findings, however, it is suggested that of primary importance is the location of the meniscus in relation to the fracture site. It is proposed that the meniscus normally serves as a barrier to prevent fusion of the distal fragment with the glenoid fossa, and that ankylosis generally occurs if this relationship is not maintained. Based on this concept, possible modifications in the management of fractures of the condyloid process are suggested.


Surgical treatment of mandibular joint disorders. This paper deals with the operations available for disorders of the temporomandibular joint. It mentions the criteria and techniques for doing these operations, namely high condylectomy, augmentation, interposition grafts and rib grafts and reviews the results of a 15-year follow-up on 64% of 130 patients on whom the author has operated.


Physiotherapy in diagnosis and treatment of the myofascial pain dysfunction syndrome. Thirty-four patients with the Myofascial Pain Dysfunction (M.P.D.) syndrome of the masticatory system were investigated and treated using physiotherapy techniques. Resisted static contraction of the temporomandibular joints, passive movement tests of the muscles and electromyography indicated that the joint function was abnormal in all cases with minimal muscle involvement. Cervical spine tests indicated that pain referral from the cervical spine was involved in 19 of 34 patients (56%). Physiotherapy treatment armed at restoring a normal painless range of movement to the temporomandibular joint was successful in six of 10 patients (60%). Generalized relaxation therapy with biofeedback was successful in 19 of 24 patients (80%). It was found that with the five of 24 patients (20%) in whom generalized relaxation failed, there were significant psychiatric factors.


Release of mandibular ankylosis due to gross tissue loss in the cheek. Experience with mandibular ankylosis due to the loss of variable amounts of cheek tissue as a result of cancrum oris is reviewed. Where enough cheek has been lost to cause an ankylosis, replacement tissue in the form of a graft is necessary to prevent recurrence and to reconstruct the cheek. A number of methods are reviewed, including free grafts, local flaps and pedicled skin from the neck and abdomen. The best functional and cosmetic result was obtained by using a tubed pedicle of abdominal skin based on the superior epigastric artery and attached to the wrist as a carrier. This can be raised under local anaesthesia prior to the release of the ankylosis so it is available to cover the raw surfaces and to reform the cheek at the time of operation. Blind intubation was found to be feasible and desirable when compared with administering the anaesthetic through a trachesotomy. The importance of close supervision of post-operative exercises is emphasized, but was not able to be carried out under the conditions of treatment.


Reconstruction of the horizontal rami of the mandible following avulsion in childhood. A 7-year-old boy was involved in a road traffic accident in October 1971, and apparently had been dragged along face downwards with resultant avulsion of the entire horizontal mandibular rami, and most of the mandibular alveolar soft tissue and teeth. Repair by metal implants was attempted but these proved unsatisfactory, and soft tissue replacement for the missing alveolus was carried out by flap raised from arm. Rib grafting was carried out on three occasions at almost yearly intervals, but each time, probably owing to vascular insufficiency, non-union (or more correctly non-replacement) occurred in the left canine region. To "import" a new blood supply, and free some of the scar tissue, a compound muscle/bone/skin flap bearing the clavicle and sternomastoid muscle was transposed to the mandibular bed. This form of grafting was used extensively in World War I to repair facial gunshot wounds, and the transposed blood supply enabled success in the pre-antibiotic period. Bony union is now satisfactory 5 years after injuries and dentures have been recently fitted; speech is normal, the child's facial contours acceptable, and mastication has been satisfactory during this period.


Objective measurement of post-operative swelling. Numerous investigators have investigated medicaments claimed to reduce post-operative edema. The majority of these investigators utilized subjective measurements which are of doubtful statistical significance. A number of objective methods of measuring oedema following surgical removal of impacted wisdom teeth are reported. The results obtained from these methods were compared and a definite correlation between them was found. A sample of 600 patients was investigated for this purpose.


Immediate temporary reconstruction of mandibular continuity defects in cancer patients. A technique is described in detail which will produce a predictable immediate temporary reconstruction of a mandibular continuity defect. The procedure is quick, inexpensive and reliable. A review of various methods of reconstruction is presented and compared with our technique. Complications are discussed. A review of our patients is presented.


Follow-up investigation of reconstruction of the alveolar process in the atrophic mandible. In this article the results are presented of the reconstruction of the alveolar process with iliac crest bone grafts in 14 patients. In all cases in a second operation a vestibuloplasty and a floor-of-mouth plasty was done. After an average follow-up period of 39 months, almost complete resorption of the bone grafts was observed. The clinical results varied. To obtain better results and avoid complications like pain at the donor and graft sites, mental nerve disturbances and other major problems associated with bone grafting, we prefer to perform the visor osteotomy in the future.


Modern trends in cryosurgery of bone in the maxillo-facial region. There have been described a variety of methods of freezing bone in the maxillo-facial region with the object of eradicating neoplastic or other abnormal cellular elements, without the need for radical excision. Thermography allows analysis of penetration so that a suitable method can be chosen for a particular clinical situation. Sequestration and pathological fracture can occur as complications but may be avoided by attention to technique.


Variations in acute multifocal histoplasmic choroiditis in the primate. Experimental histoplasmic choroiditis was produced in primates by intracarotid injections of living H. capsulatum organisms. The severity of the choroiditis varied with inoculum size, as well as with site of injection (common carotid vs. internal carotid artery). A reproducible model of histoplasmic choroiditis in primates was produced with an internal carotid injection of 5,000 to 10,000 organisms/lb. The clinical and histopathological course of this acute choroiditis over the first 30 days is presented.


Histologic analysis of photochemical lesions produced in rhesus retina by short-wave-length light. The photopathology of retinal lesions produced by extended exposure (1000 sec) to low corneal power levels (62 microW) of blue light (441 nm) was investigated by light microscopy in 20 rhesus eyes over an interval ranging from 1 hr to 90 days after exposure. Results indicate a nonthermal type of photochemical lesion originating in the retinal pigment epithelium and leading to a histological response with hypopigmentation which requires 48 hr to appear. This type of lesion helps to explain solar retinitis and eclipse blindness and has significance for aging and degenerative changes in the retina.


Herpetic keratitis. Proctor Lecture.

Herpetic keratitis. Proctor Lecture. Although much needs to be learned about the serious clinical problem of herpes infection of the cornea, we have come a long way. We now have effective topical antiviral drugs. We have animal models which, with a high degree of reliability, clearly predict the effect to be expected clinically in man, as well as the toxicity. We have systemically active drugs and the potential of getting highly active, potent, completely selective drugs, with the possibility that perhaps the source of viral reinfection can be eradicated. The biology of recurrent herpes and stromal disease is gradually being understood, and this understanding may result in new and better therapy of this devastating clinical disease.


Intercellular junctions in the ciliary epithelium. The fine structure of the intercellular junctions in the ciliary epithelium of rhesus monkeys and rabbits was studied with conventional electron microscopy of thin-sectioned specimens and the freeze-fracturing technique. In the rhesus monkey, a zonula occludens, zonula adhaerens, gap junctions, and desmosomes interconnect the nonpigmented cells, whereas gap junctions, puncta adhaerentia, and desmosomes connect pigmented to nonpigmented cells, and pigmented cells to one another. In the rabbit, desmosomes are absent between nonpigmented cells, and substituted for by puncta adhaerentia. The zonula occludens between nonpigmented cells greatly varies in its complexity in different regions of the cell perimeter, and in places, it may consist of very few intramembrane strands; this suggests that the ciliary epithelium is relatively leaky to ions and small molecules. Gap junctions are ubiquitous in the ciliary epithelium and particularly numerous at the interface between pigmented and nonpigmented layers; this finding indicates that the cells of the ciliary epithelium are joined in a metabolic syncytium. All gap junctions are characterized by the crystalline configuration which is typical of the uncoupled state; furthermore, in specimens fixed by immersion, they may be caused by uncoupling and take place in the time interval elapsing between interruption of the blood supply and arrival of the fixative fluid. Puncta adhaerentia resemble zonulae adhaerentes in their structural details but are macular in shape instead of encompassing the cell perimeter in a beltlike fashion. In contrast with desmosomes, the intercellular cleft of puncta adhaerentia has an irregular width and contains opaque material, but this never gives rise to the central band typical of desmosomes. On the inner aspect of the junctional membranes, there is a layer of fluffy material but no plaque of insertion for a bundle of tonofilaments. Finally, puncta adhaerentia have no representation in the interior of the plasmalemma and are intimately associated with cytoplasmic microfilaments. They probably anchor to the plasmalemma the contractile apparatus of the ciliary epithelial cells.


Pigment epithelial windows and drusen: an animal model. Aging rhesus monkeys, both controls and those undergoing long-term administration of investigational oral contraceptive steroids, developed widespread hyperfluorescent dots at the posterior pole. The dots were considered to represent drusen. Histologic (including electron microscopic) study showed the "drusen" in some of the animals to be almost exclusively pigment epithelial windows produced by a lipoidal degeneration of the pigment epithelial cells. The experiment provided a fortuitous model for direct correlation of clinical and histologic observations of myriad uniform, tiny, depigmented, hyperfluorescent, nonleaking spots at the level of the retinal pigment epithelium.


Pathogenesis of experimental Pseudomonas keratitis in the guinea pig: bacteriologic, clinical, and microscopic observations. Uniformly severe corneal infections were produced in guinea pigs by intracorneal injection of about 10 viable Pseudomonas aeruginosa. After a brief lag period, multiplication of bacteria was rapid, reaching geometric means of 280,000 after 24 hr and of 5 million after 48 hr. Within 8 hr after inoculation, polymorphonuclear leukocytes (PMNs) began to infiltrate the anterior two thirds of the stroma. Stromal cells adjacent to the injection site became necrotic and appeared to be engulfed by PMNs. By 14 to 16 hr, an abscess containing a dense aggregate of PMNs and multiplying bacteria developed in the central stroma. By 16 to 24 hr, collagen breakdown was apparent within and around the abscess. Ultrastructural evidence of collagen breakdown included loss of intact collagen fibrils, tactoid formation, and accumulation of amorphous electron-dense material. The area of liquefactive necrosis gradually enlarged, and many corneas perforated after 3 to 4 days. Because the course of infection is highly reproducible, this model should prove useful for many studies of experimental Pseudomonas keratitis.


Bacteriologic cure of experimental Pseudomonas keratitis. Two long-term therapy trials with high concentrations of antibiotic were carried out to determine the duration of therapy required to achieve bacteriologic cure of experimental Pseudomonas keratitis in guinea pigs. In the first study, corneas still contained Pseudomonas after 4 days of continual topical therapy with either tobramycin 400 mg/ml, amikacin 250 mg/ml, ticarcillin 400 mg/ml, or carbenicillin 400 mg/ml. In an 11-day trial of topical therapy with tobramycin 20 mg/ml, 34 of 36 corneas grew no Pseudomonas after 6 or more days of therapy. The bacteriologic response to therapy in this model occurred in two phases. About 99.9% or more of the organisms in the cornea were killed in the first 24 hr of therapy. The numbers of bacteria remaining in the cornea declined gradually over the next several days until the corneas were sterile. Optimal antibiotic therapy may include two stages: initial intensive therapy with high concentrations of antibiotic applied frequently to achieve a large rapid decrease in numbers of organisms in the cornea, followed by prolonged, less intensive therapy to eradicate organisms and prevent relapse.


Unusual evidence of myocardial involvement during a hypersensitivity reaction to oral penicillin. A hypersensitivity reaction to orally administered phenoxymethyl penicillin is reported. The manifestations of the reaction included fever, arthralgia, urticaria and an irregular pulse. Serial ECG showed second-degree atrioventricular block with junctional escape beats, an atypical Wenckebach pattern and, finally, first-degree atrioventricular block with gradually decreasing PR intervals. A normal tracing was recorded on the sixth day despite the persistence of the rash and joint pains.


Renal function during treatment of inappropriate secretion of antidiuretic hormone with demeclocycline. Two patients with the syndrome of inappropriate secretion of antidiuretic hormone were studied in a metabolic ward during treatment with 1.2 g demeclocycline daily. In both patients, demeclocycline treatment led to increased renal water excretion with consequent correction of hyponatremia and hypo-osmolality. Three episodes of reversible deterioration in glomerular filtration rate developed in these patients. Each episode was accompanied by clinical evidence of extracellular fluid volume contraction, and on each occasion there was an inappropriate natriuresis with daily urinary sodium excretion remaining above 50 mEq. Although demeclocycline effectively reverses the electrolyte abnormalities of this syndrome, the potentially dangerous side effects that may develop exclude the routine usage of the drug.


Use of out-of-plan services by Medicare members of HIP. Use of out-of-plan services in 1972 by Medicare members of the Health Insurance Plan of Greater New York (HIP) is examined in terms of the demographic and enrollment characteristics of out-of-plan users, types of services received outside the plan, and the relationship of out-of-plan to in-plan use. Users of services outside the plan tended to be more seriously ill and more frequently hospitalized than those receiving all of their services within the plan. The costs to the SSA of providing medical care to HIP enrollees are compared with analogous costs for non-HIP beneficiaries, and the implications for the organization and financing of health services for the aged are discussed.


[Differential therapy of vesico-intestinal fistulas]. 40 patients with vesico-intestinal fistulas (50% inflammatory, 30% traumatic, 20% neoplastic) were treated within 10 years. Closure was achieved in 97% of 31 patients operated on with curative intention. The remaining 9 patients had palliative surgery, i.e. colostomy or cystostomy. The decision single- or multiple-stage procedure depends upon the etiology, localization and extent of the fistula.


Norwalk agent-like particles associated with gastroenteritis in human beings. Currently, 6 agents of viral gastroenteritis with properties similar to the Norwalk agent have been described. These are the Hawaii, Montgomery County, W, Ditchling, and Cockle agents, as well as the Norwalk agent. These agents are 25 to 27 nm in diameter, are nonenveloped, and have a buoyant density of 1.38 to 1.40 g/cc in CsCl. Multiple antigenic types exist among these agents. These particles have been detected by immune electron microscopy in feces of acutely ill patients. None has been successfully cultivated in vitro, and suitable animal models of disease do not exist. Studies in volunteers indicate that acute infection is associated with a reversible histopathologic change in the jejunal mucosa and with transient malabsorption. Pathogenesis of these changes remains unknown. Other similar agents will likely emerge from ongoing studies.


The fine structural organization of the cuneate nucleus in the monkey (Macaca fascicularis). The fine structure of the cuneate nucleus of the monkey (Macaca fascicularis) has been studied. The neurons were classified into three groups according to their nuclear morphology, the arrangement of the rough endoplasmic reticulum (RER) and the appearance of the Golgi complexes. Group I neurons had a regular nucleus and contained abundant cytoplasm in which were found well-developed RER and Golgi complexes. Group II neurons had a slightly irregular nucleus and a variable arrangement of the RER and Golgi complexes. Group III neurons were characterized by a deeply indented nucleus, and scanty cytoplasm in which the cytoplasmic organelles were poorly developed. Group II neurons were the most commonly encountered while Group I neurons were the rarest. Axon terminals contained either round of flattened vesicles. Axon terminals and dendrites commonly formed synaptic complexes. In one type the axon terminal, containing round vesicles, formed the central element, which is presynaptic to the dendrites surrounding it; in addition it is postsynaptic to axon terminals containing flattened vesicles. In another type a large dendrite formed the central element which is postsynaptic to axon terminals containing round or flattened vesicles.


Amino acid sequences of the alpha and beta chains of adult hemoglobin of the slender loris, Loris tardigradus. alpha and beta chains from adult hemoglobin of the slender loris (Loris tardigradus) were isolated by Amberlite CG-50 column chromatography. After S-aminoethylation, both chains were digested with trypsin and the amino acid sequences of the tryptic peptides obtained were analyzed. Further, the order of these tryptic peptides in each chain was deduced from their homology with the primary structures of alpha and beta chains of human adult hemoglobin. Comparing the primary structures of the alpha and beta chains of adult hemoglobin of the slender loris thus obtained with those of adult hemoglobin of the slow loris, 4 amino acid substitutions in the alpha chains and 2 in the beta chains were recognized.


A new hydrolase specific for taurine-conjugates of bile acids. Through the investigation of the bile acid-deconjugation activities of human intestinal anaerobes, a new enzyme was discovered in Peptostreptococcus intermedius which hydrolyzed specifically the taurine-conjugates, but not the glycine-conjugates of bile acids. However, the enzymes in Streptococcus faecalis and Lactobacillus brevis hydrolyzed chiefly the glycine-conjugates.


Carbohydrate on human factor VIII/von Willebrand factor. Impairment of function by removal of specific galactose residues. Human factor VIII/von Willebrand factor protein containing 120 +/- 12 nmol of sialic acid and 135 +/- 13 nmol of galactose/mg of protein was digested with neuraminidase. The affinity of native factor VIII/von Willebrand factor and its asialo form for the hepatic lectin that specifically binds asialoglycoproteins was assessed from in vitro binding experiments. Native factor VIII/von Willebrand factor exhibited negligible affinity while binding of the asialo derivative was comparable to that observed for asialo-alpha1-acid glycoprotein. Incubation of asialo-factor VIII/von Willebrand factor with Streptococcus pneumoniae beta-galactosidase removed only 62% of the galactose but abolished binding to the purified hepatic lectin. When the asialo derivative was incubated with purified beta-D-galactoside alpha2 leads to 6 sialyltransferase and CMP-[14C]NeuAc, only 61% of the galactose incorporated [14C]NeuAc. From the known specificites of these enzymes, it is concluded that galactose residues important in lectin binding are present in a terminal Gal/beta1 leads to 4GlcNAc sequence on asialo-factor VIII/von Willebrand factor. The relative ristocetin-induced platelet aggregating activity of native, asialo-, and agalacto-factor VIII/von Willebrand factor was 100:38:12, respectively, while procoagulant activity was 100:100:103.


Immunological comparison of the proteins of chicken and rat liver ribosomes. A comparison of the proteins of chicken and rat liver ribosomes using immunochemical techniques was undertaken. The procedures included quantitative precipitation, passive hemagglutination, and immunodiffusion on Ouchterlony plates. The results indicate that antisera specific for chicken or rat liver ribosomes recognize only about 20% of common determinants. While there are important reservations, the results suggest extensive differences in the proteins of rat and chicken liver ribosomes. Despite those differences, rat and chicken liver ribosomal proteins maintain some homologous sequences present in bacterial ribosomal proteins. An enriched antibody preparation against chicken 80 S ribosomes inhibited the poly(U)-directed synthesis of polyphenylalanine and the elongation factor G (EF-G)-catalyzed binding of [3H]GDP to Escherichia coli ribosomes. Thus, chicken liver ribosomes, like ribosomes from rat liver and yeast, must have proteins homologous with those of E. coli ribosomes.


Homogeneous pyruvate kinase isolated from yeast by two different methods is indistinguishable from pyruvate kinase in cell-free extract. In this report, we have compared homogeneous yeast (Saccharomyces cerevisiae) pyruvate kinase to enzyme from cell-free extracts in several different ways: 1) isoelectric focusing of cell-free extracts indicates one peak of pyruvate kinase activity whose isoelectric point is the same as that of the pure enzyme; 2) antibody prepared to the pure enzyme produces a single, fused precipitin line against enzyme in the cell-free extract and pure enzyme; 3) immunoelectrophoresis of cell-free extract produces one precipitin arc which has the same mobility as that of the pure enzyme; and 4) immunoprecipitation of the pure enzyme from cell-free extract with subsequent solubilization in 1% sodium dodecyl sulfate and electrophoresis on sodium dodecyl sulfate-polyacrylamide gels produces a single protein band attributable to pyruvate kinase which co-migrates with the purified enzyme. Within the limits of the sensitivity of the methods employed, we conclude that the homogeneous pyruvate kinase prepared from yeast lysed either by Manton-Gaulin homogenization (Aust, A., Yun, S.-L., and Suelter, C. (1975) Methods Enzymol. 42, 176-182) or by toluolysis (Yun, S.-L., Aust, A.E., and Suelter, C.H. (1977) J. Biol. Chem. 251, 124-128) is identical with pyruvate kinase in cell-free extract.


Utilization of exogenous purine compounds in Bacillus cereus. Translocation of the ribose moiety of inosine. Intact cells of Bacillus cereus catalyze the breakdown of exogenous AMP to hypoxanthine and ribose 1-phosphate through the successive action of 5'-nucleotidase, adenosine deaminase, and inosine phosphorylase. Inosine hydrolase was not detectable, even in crude extracts. Inosine phosphorylase causes a "translocation" of the ribose moiety (as ribose 1-phosphate) inside the cell, while hypoxanthine remains external. Even though the equilibrium of the phosphorolytic reaction favors nucleoside synthesis, exogenous inosine (as well as adenosine and AMP) is almost quantitatively transformed into external hypoxanthine, since ribose 1-phosphate is readily metabolized inside the cell. Most likely, the translocated ribose 1-phosphate enters the sugar phosphate shunt, via its prior conversion into ribose 5-phosphate, thus supplying the energy required for the subsequent uptake of hypoxanthine in B. cereus.


Heterotopic ossification around the hip in spinal cord-injured patients. A long-term follow-up study. Twenty patients with spinal cord injury complicated by ossification around the hip were followed for eighteen months or more. The bone scan, roentgenogram, level of alkaline phosphatase, and range of hip motion of each patient were analyzed. The average follow-up was forty months. The heterotopic ossification usually did not mature until after one and one-half years. The roentgenograms were of no value in judging its maturity. The bone scan correlated well with the results of the alkaline phosphatase testing in judging maturity of the ossification. We concluded that before operative resection, a patient should have a normal level of alkaline phosphatase, decreasing activity on the bone scans, and a restriction of motion to less than 50 degrees of hip flexion.


Effects on intact femora of dogs of the application and removal of metal plates. A metabolic and structural study comparing stiffer and more flexible plates. Studies of flexible plates made of plastic have shown that less osteoporosis develops beneath them than beneath rigid metal plates. However, to date plastic plates of appropriate physical properties and biocompatibility are not available for use in humans. To determine if a similar beneficial effect could be obtained using metal plates, the effects of thick chromium cobalt plates were contrasted in experiments in dogs with the effects of thinner plates of similar design made of titanium, 6-aluminum, 4-vandium. A significant reduction in the osteoporosis was obtained by use of the more flexible plates. Following plate application a delayed, massive, transient stimulus to bone formation occurred endosteally, periosteally, and intracortically. Despite this, a substantial decrease in bone mass occurred, primarily mediated by endosteal bone resorption. Intracortical porosity played little or no role in net bone loss. The major effects subsided by six months. Recovery after plate removal was predominantly the result of endosteal new-bone formation.


Freeze-fracture studies of the developing cell surface. II. Particle-free membrane blisters on glutaraldehyde-fixed corneal fibroblasts are artefacts. We describe, in sections and by freeze-fracture, four classes of intramembrane particle (IMP)-free membrane blebs or "blisters" associated with glutaraldehyde-fixed embryonic corneal fibroblasts: (a) Single blisters attached to the cell membrane; (b) free (detached) vesicles; (c) myelin figures; (d) multivesicular protrusions which resemble the "mounds" described by others on nerve growth cones. The IMP-free, membrane-bounded blisters contain no ground cytoplasm or organelles, in contrast to blebs on trypsin-isolated fibroblasts, which we show here do contain cytoplasm and IMP-rich membranes. That the IMP-free membrane blisters in embryonic corneas are artefacts of fixation is demonstrated by (a) their absence in replicas of fibroblasts frozen and fractured without prior aldehyde fixation and (b) their absence in sections of fibroblasts fixed in a combination of glutaraldehyde and osmium tetroxide. We suggest that the addition of osmium prevents postfixation movement of membrane lipids, especially the negatively charged "fluid" lipids which others have shown are capable of considerable mobility after aldehyde fixation alone. Recent literature has implicated membrane blistering in secretory processes and in growth of nerves, but before the functional significance of such IMP-free blisters is assessed, membrane mobility of the type shown here should be taken into consideration.


Isolation and partial characterization of Drosophila myoblasts from primary cultures of embryonic cells. We describe a method for preparing highly enriched cultures of Drosophila myoblasts from a heterogeneous cell population derived from gastrulating embryos. Enriched cultures are prepared by plating this heterogeneous population of cells in medium from which much of the free calcium is chelated by ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetate (EGTA). Adhesion of myoblasts to tissue culture plastic is better than that of other cell types when plated in this medium. Data concerning cell identity, timing of S phase, and fusion kinetics document the degree of enrichment for myogenic cells and illustrate their synchronous differentiation in vitro.


Ultrastructure of meiosis-inducing (heterotypic) and non-inducing (homotypic) cell unions in conjugation of Blepharisma. Cells of mating types I and II of Blepharisma japonicum interact with each other and unite in heterotypic (type I-type II) or homotypic (type I-type I, type II-type II) pairs. Heterotypic pairs undergo meiosis and other nuclear changes of conjugation, while homotypic pairs remain united for days without the nuclear changes taking place. We compared cell unions of these two kinds of pairs at the ultrastructural level. In the homotypic union, cell membranes are closely juxtaposed, separated by a distance of about 20 nm. This arrangement is interrupted in some places by vacuoles and small cytoplasmic bridges. Saccule-like structures tend to be more abundant near the united surfaces. Microtubules running at right or slightly obtuse angles with the cell surface (PACM microtubules) are characteristically present at the united region of cells. These structures are very similar to those observed in earlier stages of the heterotypic union. However, in homotypic pairs, cells unite only at the anterior half of the peristome, while in heterotypic pairs cells unite also at the posterior half of the peristome, where the cell membrane totally disappears in later stages. PACM microtubules persist for at least 18 h in homotypic unions, while they disappear within a few hours in heterotypic unions. These differences between the two kinds of cell union are discussed in relation to the initiation mechanism of meiosis and other nuclear changes of conjugation. Similarities between homotypic union and cell junctions in multicellular organisms are also discussed.


Rapid identification of Actinomycetaceae and related bacteria. Identification of new isolates belonging to the family Actinomycetaceae requires extensive numbers of biochemical tests, supplemented with gas-liquid chromatography determination of fermentation end products and, often, analysis of cell wall composition. This paper describes the results of the testing of 162 strains of Actinomycetaceae and related taxa for 20 different enzymatic activities including phosphatases, esterases, aminopeptidases, and glycosidases. The results of all tests were read after 4 h of incubation. The results obtained in the study provide significant new information on the biochemical properties of these groups of bacteria. An identification scheme based upon 13 selected tests, which allow the identification of these groups of bacteria within 4 h, is proposed.


Immunoglobulin-specific radioimmunoprecipitation assays for quantitation of nasal secretory antibodies to hemagglutinin of type A influenza viruses. Radioimmunoprecipitation (RIP) assays were developed to selectively quantitate class-specific antibodies to purified hemagglutinins (HA) of type A influenza virus in nasal secretions. Rabbit anti-human secretory piece of immunoglobulin A (IgA) and rabbit anti-human IgG were used as second antibodies. A third antibody, goat anti-rabbit IgG, was incorporated into the system to separate immune complexes formed between iodinated HA, nasal wash test specimen, and second antibody. The utilization of this reagent avoided the need for large quantities of IgA and IgG antibody-negative carrier secretions. Nasal was specimens obtained from 14 adults immunized with an inactivated type A influenza virus vaccine were evaluated by RIP and viral neutralization assays. Significant homologous postvaccination secretory IgA and IgG antibody levels were demonstrable in 13 (93%) of individuals by RIP, whereas only 5 (36%) exhibited rises by viral neutralization tests. Moreover, the geometric mean IgA and IgG antibody levels were at least 20- and 37-fold greater than the neutralizing antibody titer. The pattern of heterologous immunoglobulin-specific antibody responses tended to be similar to those observed with the homologous HA subunit.


Serological classification of Pseudomonas aeruginosa by a slide agglutination test. Serological classification of Pseudomonas aeruginosa by the slide agglutination test with live organisms was studied, based on the O antigen schema adopted by the international expert panel sponsored by the Subcommittee on Pseudomonas and Related Organisms of the International Committee on Systematic Bacteriology. The typing results obtained by the slide test with well-absorbed O sera were identical to those obtained by the conventional tube agglutination test with autoclaved organisms. Most O antigens occur singly; but O2, O5, and O16 occur in four combinations. Antigens O13 and O14 are closely related, as are O7 and O8, and it would be convenient to classify organisms possessing these antigens collectively as O7,8 and O13,14.


[Digestive insufficiency and artificial feeding. Theoretical and practical aspects (author's transl)]. The relatively new concept of digestive insufficiency was born as a result of prolonged artificial nutrition. Digestive insufficiency may be of organic, functional or mixed nature; its medical and surgical causes are numerous. Artificial nutrition has become a major therapeutic adjuvant in all types of digestive insufficiency. By acting as a substitute for the intestinal function, artificial nutrition permits better tolerance of specific treatments thanks to the nutritional rehabilitation and intestinal rest which it provides for as long as the patients' malnutrition and digestive lesions make it necessary.


Detection of antibody to bovine syncytial virus and respiratory syncytial virus in bovine fetal serum. Batches of commercial fetal bovine serum, described by the suppliers as antibody-free, all contained antibody to bovine syncytial virus (BSV) when tested by indirect immunofluorescence. Antibody to bovine respiratory syncytial virus (RSV) was not detected in these sera. Twenty-four percent of individual fetal bovine sera contained antibody to BSV, and 14% contained antibody to RSV when tested by indirect immunofluorescence. BSV antibody titers in fetal sera from dams with high BSV antibody levels were variable but always higher than RSV antibody titers. Radial immunodiffusion studies with BSV-positive sera revealed the presence of immunoglobulin M (IgM), IgG, and IgA, but the quantity of these immunoglobulins was not directly related to the BSV antibody titers. The evidence suggests that the antibody present in fetal sera arose as the result of infection rather than from maternal transfer across the placenta.


Identification of Rickettsia rickettsii in formalin-fixed, paraffin-embedded tissues by immunofluorescence. With slight modification of a trypsin digestion technique, Rickettsia rickettsii were demonstrated specifically by immunofluorescence staining in Formalin-fixed, paraffin-embedded tissue sections from a human, rhesus monkey, and guinea pig with Rocky Mountain spotted fever and in infected membranes from a chicken embryo. Tissues were cut at 4 micron and, using geltain as a tissue adhesive, were hydrated in a routine manner. Sections were then digested in refrigerated 0.1% trypsin for 16 h, washed, and stained specifically for R. rickettsii by direct or indirect immunofluorescence. Rickettsial organisms were localized in affected vessels of the mammalian species and within the yolk sac epithelium of the chicken embryo. Specificity was confirmed by adsorbing antibody conjugates with R. rickettsii organisms. Trypsin digestion probably decreased tissue proteins which interfered with immunochemical attachment of antibody to the rickettsiae. The technique is valuable in that a diagnosis of Rocky Mountain spotted fever can be confirmed from Formalin-fixed tissues processed in a routine manner.


Enzymatic and immunological characterization of the Mycobacterium fortuitum complex. The arylsulfatase isozymes of Mycobacterium fortuitum, M. peregrinum, M. chelonei subsp. chelonei, and M. chelonei subsp. abscessus were examined to determine the isozymal and immunological relationship among the members of the M. fortuitum complex. Cell extracts were subjected to electrophoresis on agarose and polyacrylamide gel, and arylsulfatase activity was localized using beta-naphthyl sulfate as substrate. Unique zymograms were produced for M. fortuitum, M. peregrinum, and M. chelonei which were characteristic for each species. The immunological relationship among the sulfatases was assayed by using immunodiffusion and immunoelectrophoresis followed by sulfatase staining for the enzyme. One of the isozymes of M. fortuitum and M. peregrinum cross-reacted, showing immunological identity. Antisera to sulfatases of M. fortuitum and M. peregrinum did not react with sulfatases of M. chelonei. The characterization of sulfatase isozymes in extracts of organisms in the M. fortuitum complex suggests the division of the M. fortuitum complex into two species, M. fortuitum and M. chelonei, with subspecies designations.


Identification of Neisseria gonorrhoeae from primary cultures by a slide agglutination test. Hen antigonococcal lipopolysaccharide hen serum was used in a simple slide agglutination test for the identification of Neisseria gonorrhoeae from primary isolates.


Third component, HBeAg/3, of hepatitis B e antigen system, identified by three different double-diffusion techniques. A third component, HB(e)AG/3, of the hepatitis B e antigen system has been detected, and it was consistently detected in three variations of the double-diffusion technique.


Gray scale B scan characteristics of intra-abdominal cystic masses. A comparison of the gray scale characteristics of 119 intra-abdominal cystic masses was performed. Each cystic mass was evaluated with regard to: 1) The presence or absence of internal echoes, septa, and fluid-fluid levels; 2) The appearance of the wall; 3) Conformity to adjacent organs and, 4) Changes in the surrounding soft tissues. Abscesses, hematomas, lymphoceles, urinomas, and necrotic tumors were evaluated. Necrotic tumors and some abscesses and hematomas have specific sonographic characteristics. In most cases, a definite diagnosis cannot be made from the sonographic appearance; however, in conjunction with the clinical history, the differential diagnosis can be narrowed to a couple of cystic lesions among the many that may be found in the abdomen. The diagnosis can be confirmed by aspiration under ultrasound. A comparison between these cystic masses and pancreatic pseudocysts, renal cysts, and ovarian cysts was made.


Ultrasonographic demonstration of glaucomatous optic nerve excavation. Advanced glaucomatous excavation of the optic nervehead can be demonstrated reliably with contact B scan ultrasonography; large physiologic cups do not produce an abnormal optic nervehead pattern. Demonstration of a depression at the surface of the optic nerve insertion must be interpreted as indicative of glaucomatous excavation but should not be used as a contraindication to surgery.


Ultrasonic planimetry of the gestation sac as a biometric method in early pregnancy. A new method for determining the area of the gestation sac by thread planimetry is described. Mean weekly values with two standard deviations were determined on a series of 237 measurements of gestation sac area, age five to 11 weeks, in normal pregnancies. The gestation sac area grows curvilinearly from 1.85 cm2 at five weeks to 15 cm2 at 11 weeks. The mean diameter was calculated from the gestation sac area by using an adequate approximation of the irregular gestation sac shape to a circle of the same area. The dependence of the mean gestation sac diameter on gestation age is defined by the regression equation y = 0.46x - 0.95 and the correlation factor r = 0.92. Practical applications of gestation sac planimetry include the determination of gestation age in early pregnancy, and the follow-up of growth or determination of delayed growth in disturbed or failed early pregnancy.


Limitations in prediction of gestational age and birth weight by ultrasonographic methods. The index of predictability of estimated gestational age (EGA) and birth weight (BW) from biparietal diameter (BPD) was tested in 1333 normal pregnancies; 96% of the patients were black. The correlation BPD and actual weeks to delivery was 0.834, r2 =69.5%. Confidence limits were established and a nomogram for EGA was derived. Our nomogram and two similar ones were compared. The overall correlation between them was good, but that for specific BPD and EGA was not. In addition, our BPD values were smaller for corresponding gestational ages in other nomograms. The overall accuracy of estimated delivery date was +/- 1.6 weeks. We were not able to predict birth weight at all from a single, random BPD measurement. We have demonstrated the serious limitations that exist in the prediction of gestational age from previously established nomograms. We infer that this error is even greater when homogenous populations are so studied. We suggest that any published BPD-EGA or BPD-BW nomogram be given close, intensive statistical scrutiny, within the population studied, before it is used. When such scrutiny is not possible, serial sonographic determinations, or longitudinal use of growth charts, would be more acceptable.


The influence of ultrasound on the frequency of amniocentesis. To determine the effect of development of ultrasonographic guidance techniques on the frequency of amniocentesis, we compared two two-year periods before and after the use of ultrasound. Statistically significant decreases in both the number of amniocenteses ordered and the number performed were observed. We concluded that ultrasound has been judiciously used and has not prompted an increased use of amniocentesis merely because of improved ease and safety. A slight decrease in the perinatal mortality rate mitigates against any compromise in the standard of antenatal care.


Private practice use of real-time B scan ultrasound in obstetrics and gynecology. An informal survey of 25 obstetrics and gynecology practices that use real time B scan ultrasound equipment was carried out to assess the economic and patient-care impact of such equipment. From this informal survey, it can be seen that the incorporation of real time B scan ultrasound scanning into private practice has become economically feasible and useful for the daily clinical management of obstetric patients. The implications and economics of such changes for obstetric health care costs remain to be assessed.


Signs of fetal death in early pregnancy. The principal ultrasonic signs of death of the fetus in the first 12 weeks of pregnancy are reviewed and illustrated. Several new signs, one probably due to CO2 in the conceptus, are recorded. The use of two-dimensional B scanning and multiplanar stereoscopic sonar is made.


Ultrasonic calculation of chorion cavity volume. A method for calculating chorion cavity volume in the first trimester of pregnancy from the ultrasonic projection of the gestation sac is described. The area of the longitudinal and transverse sections were measured, and the volume was calculated from the mean value of the two measurements. The chorion cavity volume increased curvilinearly and approximately exponentially from 2.14 cc at five weeks to 44.38 cc at 11 weeks of gestation. The method was checked by comparing the computed volume and the real volume obtained surgically and by experimenting with an "artificial gestation sac" picture. A good correlation was obtained. The results match data reported in the literature.


Rare occurrence of a holoacardious acephalic monster: sonographic and pathologic findings. Sonography is gaining increasing importance in the diagnosis of anomalies in utero. Findings such as anencephaly, hydrocephaly, sacrococcygeal teratoma, fetal ascites, and obstructive uropathy have been described. Detection of anomalies such as these are important in the management of the pregnancy and aid in the preparation for the postnatal care or treatment of the fetus. While this article deals with the dramatic findings of a grossly anomalous fetus of a twin pregnancy, the ultimate value of ultrasound is its potential for detecting correctable malformation in a safe, noninvasive, and harmless manner.


Ultrasound evaluation of a near-term abdominal ectopic pregnancy. Ultrasound confirmation of an abdominal ectopic pregnancy was established by the demonstration of an enlarged but empty uterus and the delineation of the fetal head within the abdominal cavity. Other portions of the fetus could not be demonstrated. The margins and attachments of the placenta could not be accurately delineated prospectively.


An integrated television and real-time ultrasonic imaging system. A mechanical sector scanning ultrasonic imaging system was integrated with a video character generator and an infrared sensitve television camera to add patient data and scanner position information to a recorded ultrasonic image. A permanent record is made by recording the final composite image on video tape together with simultaneous audio of examiner's comments during examination. This has facilitated both the interpretation of scans and the relocation of the scanner on successive procedures.


The neuroanatomical organization of pathways between the dorsal lateral geniculate nucleus and visual cortex in Old World and New World primates. Pathways between the dorsal lateral geniculate nucleus (dLGN) and visual cortex in Old World (Macaca, Papio, Erythrocebus, Cercopithecus) and New World (Saimiri, Cebus) primates were studied after injections of horseradish peroxidase and H3 or S35 amino acids into the dLGN or visual cortex. Trans-synaptic autoradiography was also used to study these pathways after an injection of H3 proline-fucose into one eye. The subsequent autoradiographs of visual cortex showed that Old World primates have separate eye inputs (ocular dominance columns) in the striate cortex, whereas New World monkeys have overlapping or non-separated eye inputs. In both primate groups the geniculocortical input to layer IVA formed a pattern which resembled a honeycomb in tangential sections, unlike the solidly labeled layer IVC. Also common to the two primate groups was a projection from dLGN to layer VI. There was no dLGN projection to any prestriate area in any of the primates. However, after an injection limited to the prestriate cortex of Macaca, light autoradiographic labeling was seen in the interlaminar zones and the magnocellular and S laminae, demonstrating a prestriate-dLGN pathway. Our results indicate that the primate visual system differs significantly from the cat in having no dLGN projection to area 18. There are also signficant differences between primates in the level at which the possibility of binocularity (of an excitatory nature) first occurs in the striate cortex because in the species studied thus far with neuroanatomical methods, Old World primates have ocular dominance columns in layer IV but most New World monkeys lack them.


Cerebellar cortical efferent fibers of the paraflocculus of tree shrew (Tupaia glis). Efferent projections from the paraflocculus of the tree shrew (Tupaia glis) were studied utilizing the Fink and Heimer ('67) method. Cerebellar corticonuclear fibers of both dorsal (Dpf) and ventral (Vpf) divisions of the paraflocculus terminate in the lateral cerebellar nucelus (NL) and in the posterior interposed nucleus (NIP). These fibers are ipsilateral, topographically organized and arranged into at least two zones. Following injury to either the Dpf or Vpf, degenerated axons are found in lateral and caudal regions of the NIP respectively. Consequently, these two portions of the paraflocculus have relatively exclusive terminal fields with overlap only at the periphery. Preterminal debris is seen in basically similar areas of the NL (caudolateral, caudal, ventral) after damage to either the Dpf or Vpf. This observation leads to the conclusion that the terminal fields for these areas of parafloccular cortex are largely coextensive in the NL. In addition to the topographical representation of the Dpf and Vpf in both the NL and NIP, there is evidence that these corticonuclear fibers are also organized into the general zonal pattern hypothesized by Voogd ('69). Persistent and numerous degenerated axons from both the Dpf and Vpf end in lateral and caudal NIP, respectively, corroborating the presence of a relatively wide zone C2 in both divisions of the paraflocculus. The Dpf and Vpf also project into the NL to a terminal field that appears to consist of two portions. One part located in caudal, ventral and/or caudoventral areas of the NL and a second at slightly more rostral and rostrolateral areas. The presence of a cortical region which is affiliated with two areas of the NL substantiates not only the existence of zone D in the paraflocculus, but gives experimental evidence that it may consist of two parts as previously suggested (Voogd, '69). From the Dpf many fibers enter the NL while few are seen in this nucleus after damage to the Vpf. This suggests that zone D is wider in the Dpf and narrower in the Vpf. The results of this study do not support previous suggestions that the paraflocculus projects to either only the NL or to most of, or all of, the ipsilateral cerebellar nuclei. No projections to any contralateral cerebellar nuclei are seen. There is also no conclusive proof that the parafloccular cortex of Tupaia projects into the vestibular complex or to any other brainstem relay nuclei.


Organizational features of the cat and monkey cerebellar nucleocortical projection. The organization of the cerebellar nucleocortical projection in the cat and the monkey has been studied using orthograde and retrograde neuroanatomical tracing techniques. Injections of tritiated leucine in the cat cerebellar nuclei orthogradely labeled nucleocortical fibers throughout their course to the cerebellar cortex. Their branch points in the corpus medullare, in the folial white matter, and in the granular layer were evident from the dense, continuous distribution of silver grains overlying these labeled axons. The results from the cat showed that the cerebellar nucleocortical projection is organized principally into three rostrocaudally oriented longitudinal cortical zones. Fastigial nucleocortical fibers were directed principally to the medial 1.5-2.5 mm of the ipsilateral vermis, with a lighter projection to the lateral vermis ipsilaterally and to the medial area of the vermis contralaterally. The interposed nuclei projected mainly to the paravermis-medial hemispheric zone of the cerebellar cortex. Nucleocortical fibers from the posterior interposed nucleus projected principally to the paramedian lobule, to the medial hemispheric area of Crus I and the lobus simplex, and to the flocculus and paraflocculus. Nucleocortical projections from the anterior interposed nucleus coursed to the anterior lobe paravermis and to the ventral folia of the paramedian lobule. A lighter projection from the interposed nuceli was found to the lateral edge of the vermis and into intermediate areas of the hemisphere. Dentatocortical fibers were directed into the lateral folia of Crus I and Crus II of the lateral hemispheric zone, with a ligher projection to intermediate areas of the hemisphere of the posterior lobe and along the lateral edge of the anterior lobe hemisphere. Along the periphery of each cortical zone, the nucleocortical projection from adjacent deep nuclei overlapped slightly. The retrograde transport of horseradish peroxidase (HRP) from injection sites in the lateral hemisphere, in the medial hemisphere--paravermis, and in the vermis labeled neurons localized mainly within the dentate, interposed, and fastigial nuclei, respectively. Retrograde labeling experiments carried out in monkeys indicated that the organization of the nucleocortical projection in this species is different than that of the cat. In the primate, the nucleocortical projection to the lateral hemisphere, to the medial hemisphere--paravermis, and to the vermis appeared to arise principally from the dentate nucleus. There was a secondary input to the paravermis and vermis arising from the interposed and fastigial nuclei, respectively. This evidence suggests that the cerebellar nucleocortical system undergoes a significant phylogenetic change in its organization between the cat and primate. These organization differences are discussed in light of possible functional implications.


Utilization and cost-effectiveness of cranial computed tomography at a university hospital. This study prospectively surveyed the utilization of cranial computed tomography (CCT) at The George Washington University Hospital over a 12-month period. Of 3,070 CCT scans studied, 1,098 (35%) resulted in a positive clinically important diagnosis for an overall case finding cost of $800. Within each of 25 individual indications for scanning, classified on the basis of the patient's most specific sign or symptom, case finding costs varied from a low of $411 for patients in coma to $3,500 for patients with headaches as their only indication for CT scanning. Within two diagnostic categories, malignant brain tumors and cerebral aneurysms, there was significant agreement (p less than 0.001) between the prescanning diagnosis and the result on CCT. Overall there was also close agreement (correlation coefficient = 0.706) between the rank listing of the 25 indications for scanning compiled prior to CCT with that obtained after the scanning results were known.


Quantitative multiregional CSF kinetics using serial, metrizamide enhanced computed tomography. Two rhesus monkeys studied by serial metrizamide (Amipaque) enhanced computer tomography (CT) imaging were used to quantitatively analyze cerebrospinal fluid (CSF) kinetics in multiple anatomical regions. Time--density curves were generated for the cisterna magna, suprasellar cistern, quadrigeminal cistern, and sylvian fissure, If clinical, biochemical, and routine static CT scanning indicate a profile suggesting normal pressure hydrocephalus, then CSF kinetics may be quantitatively and dynamically studied by CT imaging with metrizamide enhancement. This multiregional approach may be applied in an attempt to accurately distinguish normal pressure hydrocephalus from cerebral atrophy as a means of predicting which patients will likely profit from surgical diversionary shunting.


Hygiene in the prevention of udder infections. IV. Evaluation of teat dips with excised cows' teats. Suspensions of Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli, and Pseudomonas aeruginosa were used to contaminate teats excised from cows. Commercially available teat dips were applied for evaluation of comparative germicidal activity. Iodophors, sodium hypochlorite, and sodium dichloro-s-triazenetrione were highly effective against all four test organisms. Quarternary ammonium, chlorhexidine, and cetylpyridinium chloride were effective against Staphylococcus aureus, and Streptococcus agalactiae but not Escherichia coli and Pseudomonas aeruginosa. Bronopol and 8-hydroxyquinoline sulfate were marginally effective on the two Gram positive organisms and ineffective on the two Gram negatives. Three of the dips were ineffective against all four pathogens; two were in nonaqueous bases, and the other was a blend of pine oil and antibodies with udder origin. In other trials, iodophor at .3% titratable iodine was highly effective against Staphylococcus aureus and Streptococcus agalactiae. Products containing .5 and 1% iodophor maintained effectiveness after each was used to dip 140 teats under conditions of commercial dairying. Logarithmic reduction in the geometric mean number of organisms recovered from teats was more meaningful for evaluating data than percent reduction.


Treatment of complicated cutaneous malignant neoplasms by modern radiotherapy: principles, practice, and results. The indispensability of modern radiotherapy for certain complicated cases of cutaneous malignant neoplasms is demonstrated by a review of its principles and demonstration of results achieved by its practice in five representative cases.


Aspirin intolerance: unaltered susceptibility of platelet cyclo-oxygenase to inhibition by aspirin in vitro. Inhibition of prostaglandin (PG) biosynthesis has been proposed as a mechanism of aspirin-induced asthma. In order to verify the existence of a generalized abnormal sensitivity of the PG cyclo-oxygenase in intolerant patients, we have compared the inhibitory effects of aspirin on platelet PGE2 and PGF2alpha spontaneous formation in vitro, in 10 healthy subjects, 10 aspirin-sensitive asthmatics, and 10 nonasthmatic aspirin-sensitive patients. No statistically significant differences were found in the pattern nor in the absolute concentrations of both PGs in the control platelet superfusates. Moreover, the synthesis and release of both PGs were inhibited by aspirin with the same potency in the three groups studied.


Multiple primary malignancy in the elderly. The longer a patient lives, the more predisposed he is to become host to primary malignant neoplasms at various sites. Hence the importance of follow-up clinics in long-term care facilities. Data on multiple malignancies at Oak Forest Hospital are presented. Among 34 such patients (average age, 72 years), 28 had malignant lesions at two primary sites, and 6 at three primary sites.


[Some aspects of prevention in perinatology (author's transl)]. The main lines in prevention are analyzed in two fields. Prevention of brain damage during birth process is studied according to the data of a prospective study, showing the obstetrical situations where the fetus is at risk. Prevention of fetal infection is shown on a few clinical examples.


Isolation of animal viruses from farm livestock waste, soil and water. Ten porcine enteroviruses, 2 porcine adenoviruses and 1 coronavirus were isolated directly from 32 samples of slurry collected from a pig fattening house. Concentration of the same samples by adsorption with the polyelectrolyte PE-60 yielded 24 porcine enteroviruses and 3 porcine adenoviruses. A porcine enterovirus was isolated, following PE-60 concentration, from 1 to 6 slurry samples from a sow farrowing house. No virus was isolated from 12 samples of slurry from dairy cows nor from 6 slurry samples from a calf-rearing unit. A porcine enterovirus was isolated from soil samples, after concentration with PE-60, collected 1, 2 and 8 days after pig slurry was spread on hay stubble. Two porcine enteroviruses were isolated by membrane filtration from 26 samples of surface run-off from land on which pig slurry was routinely spread, and 2 bovine enteroviruses were isolated from cattle feedlot run-off after adsorption to layers of talc and celite followed by hydroextraction. A porcine enterovirus was also isolated from 1 of 33 samples of surface water collected on farms on which pig slurry was routinely spread on the land, but no virus was isolated from 36 samples of ground water from the same farms. The surface water and ground water samples were concentrated by talc-celite adsorption and hydroextraction.


Nonimmunologic complement activation in normal human serum induced by radiographic contrast media. Two different radiographic contrast media (RCM), iothalamate and iodipamide, induced the activation of several complement (C) components in normal, genetically C2-deficient and agammaglobulinemic human sera in vitro. This activation was dose dependent and demonstrable by a reduction in whole C as well as C4, C2, C3, and C5 hemolytic activities. C6, C8, and C9 hemolytic activities were unaffected. Concommitant with the loss of C3 hemolytic activity was the appearance of C3 proteolytic cleavage products that were identified by immunoelectrophoresis. Both the loss of C3 hemolytic activity and the production of C3 fragments occurred in the presence of 10 mM EDTA, indicating RCM-induced C3 cleavage occurred without participation of the multicomponent C3/C5 convertases of either the classical or alternative C pathways. Furthermore, loss of C3 hemolytic activity was not due to the direct alteration of the C3 molecule by RCM because purified C3 was unaffected upon incubation with RCM at a concentration that induced 80% reduction in the C3 hemolytic activity in normal human serum. Serum samples obtained from 40 patients, before and 30 min after undergoing i.v. pyelography, revealed no significant change in total hemolytic C activity; 34 patients received sodium and methylglucamine diatrizoate and six received sodium iothalamate. Hemolytic C3 levels were also determined for the six patients before and 30 min after administration of sodium iothalamate and no significant change in activity was detectable.


Rodent malaria: BCG-induced protection and immunosuppression. One dose of 10(7) viable units of Mycobacterium bovis, strain BCG, protected a significant number of Swiss mice from a primary challenge with 10(4) thoracic sporozoites of Plasmodium berghei. Immunization with irradiated sporozoites induced greater protection than that observed in BCG-treated with BCG and surviving a primary sporozoite challenge were not protected from rechallenge, whereas mice immunized with irradiated sporozoites and surviving initial challenge of sporozoites were solidly immune to further challenge. Immunizing mice with BCG and irradiated sporozoites simultaneously resulted in a synergistic effect of increased protection against a primary challenge of sporozoites only if the two immunogens were administered on the same day and if the mice were challenged 1 to 3 days later. Mice given BCG and irradiated sporozoites and surviving a primary challenge of sporozoites were unable to survive rechallenge. BCG given to mice previously immunized with irradiated sporozoites suppressed their protective immunity against sporozoite challenge.


Estimates of the precursor frequency of cytotoxic T lymhocytes against antigens controlled by defined regions of the H-2 gene complex: comparison of the effect of H-2 differences due to intra-H-2 recombination vs mutation. Lymph node cells were sensitized in a limiting dilution assay against B10.D2 (H-2d) and the frequency of cytotoxic T lymphocyte (CTL.P) precursors was determined. A mean CTL.P frequency of 0.047% was observed when responding strains differed from the stimulators at the entire H-2 gene complex. When intra-H-2 recombinant strains were sensitized against B10.D2, lower frequencies of CTL.P were observed. Responding strains that differed from the stimulators at the H-2K-end only had 2- to 6-fold more CTL.P compared to strains sensitized against the D-end only. In order to study the CTL.P frequency against minor antigenic differences, the B10.D2 (M504-H-2da) mutant strain, which carries a mutation with an antigenic gain-loss in the D-region of H-2d, was examined. This mutant showed an identical CTL.P frequency against H-2d as H-2D-end recombinant strains. Therefore, this H-2 mutant (M504) has either undergone extensive mutation or the qualitative nature of the antigenic loss in this strain results in a high CTL.P frequency against the strain of origin.


Immunoglobulin M synthesized by human lymphoblastoid cells: interaction with Staphylococcus aureus and protein A. Immunoglobulin M synthesized by a human lymphoblastoid cell line, LA173, was found to bind specifically to the protein A-bearing Cowan I strain of Staphylococcus aureus. The (3H)-leucine-labeled, secreted IgM from these LA173 cells also formed precipitin complexes with purified protein A. Soluble complexes formed at high protein A/IgM ratios retained the ability to bind to the bacterial surface. Precipitin complexes also were observed in double diffusion Ouchterlony gels with a line of identity formed between the IgM, protein A, and anti-IgM in adjacent wells. Intracellular IgM species from detergent-lysed LA173 cells were bound to S. aureus. Labeled 19S pentamers, 8S monomers, and HL subunits were eluted from the bacteria and identified by velocity sedimentation and SDS agarose-acrylamide gel electrophoresis. In addition, several intermediates migrating between 8S and 19S were detected and shown to contain authentic H and L chains. Binding of the labeled IgM 19S pentamers to staphylococci was not inhibited by prior treatment of the bacteria with an excess of unlabeled human IgG. However, S. aureus saturated with unlabeled IgG did not bind either labeled IgM monomers or labeled IgG. The interaction of this human IgM with S. aureus exhibited a high degree of specificity with quantitative recovery of secreted 19S IgM. Intracellular IgM species were bound selectively by the bacteria with little if any contamination by other cytoplasmic proteins.


Evidence for close linkage of a mouse light chain marker with the Ly-2,3 locus. Light chains associated with normal serum immunoglobulin can be resolved into a finite number of discrete focusing bands by isoelectric focusing. Four distinct light chain patterns can be distinguished among the inbred mouse strains. In the present studies inheritance of the characteristic light chain patterns has been studied in the AKXL recombinant inbred lines (derived from C57L/J and AKR/J parental lines) and in the inbred Ly-2a,3a congenic line B6.PL-Ly-2aLy-3a/Cy as well as in individual backcross animals of an incipient Ly-2a,3a congenic strain. Virtually complete concordance was observed for the expression of light chains characteristic of phenotype B (AKR-J-like) and the expression of the Ly-2a,3a allele. This observation indicates that a locus controlling light chain structure and/or expression is closely linked (less than 2.6 map units) to the Ly-2,3 locus on mouse Chromosome 6. The locus controlling normal light chain IF-patterns has been designated Ef1.


A simple method for the preparation of antisera specific for murine immunoglobulin heavy chains. Rabbit antisera were prepared against mouse immunoglobulin mu and gamma chains by immunizing rabbits with their own erythrocytes coated with murine anti-rabbit erythrocyte immunoglobulin. In the preparation of these antisera, we exploited the observation that the primary immune response in C57BL/10ScSn (B10) mice is almost exclusively IgM, while hyperimmune antiserum of A/WySn (A) is mostly IgG. After appropriate absorption with thymocytes and rabbit erythrocytes (Rrbc) coated with B10 or A antiRrbc Ig, the sera were shown to be specific by immunoelectrophoresis, indirect immunofluorescent staining, and complement-mediated cytotoxicity. This technique is simple, requires almost no equipment, and a large quantity of specific antiserum can be prepared quite economically.


Raising of antisera to protein hormones without using Freund's adjuvant. A new method has been developed to produce antiserum to protein hormones without the use of Freund's complete adjuvant. Antiserum to human chorionic gonadotropin (hCG) was elicited by injecting rabbits with 6 subcutaneous injections of sheep red blood cells (SRBC) coated with hCG. The antiserum produced was observed to be both serologically and biologically active. A small quantity of the hormone (15--20 IU/injection) sufficed to produce hyperimmune sera. This could ensure an overall economy if large amounts of the antisera are required for clinical and diagnostic purposes.


Studies on the relationships between serum bactericidal activity and uncomplicated genital infections due to Neisseria gonorrhoeae. This report concerns the relationships between patients' uncomplicated genital infections due to Neisseria gonorrhoeae and the bactericidal activity of their sera against their infecting organisms. Forty isolates of N. gonorrhoeae and 91 serum samples were obtained from 23 patients with their first or repeated gonococcal infections. Of 32 sera obtained at the time of infection, 14 (44%) were bactericidal for the infecting strains. Of convalescent-phase sera from 27 infections, 12 (44%) were bactericidal; 22%-33% of convalescent-phase sera had increased bactericidal activity when compared with acute-phase sera or sera obtained before infection. Eleven patients developed 17 new infections after sera and negative cultures were obtained; in six (35%) the previously obtained sera were bactericidal but did not prevent infection.


Familial deficiency of the seventh component of complement associated with recurrent bacteremic infections due to Neisseria. The serum of a 29-year old woman with a recent episode of disseminated gonococcal infection and a history of meningococcal meningitis and arthritis as a child was found to lack serum hemolytic complement activity. The seventh component of complement (C7) was not detected by functional or immunochemical assays, whereas other components were normal by hemolytic and immunochemical assessment. Her fresh serum lacked complement-mediated bactericidal activity against Neisseria gonorrhoeae, but the addition of fresh normal serum or purified C7 restored bactericidal activity as well as hemolytic activity. The absence of functional C7 activity could not be accounted for on the basis of an inhibitor. Opsonization and generation of chemotactic activity functioned normally. Complete absence of C7 was also found in one sibling who had the clinical syndrome of meningococcal meningitis and arthritis as a child and in this sibling's clinically well eight-year-old son. HLA histocompatibility typing of the family members did not demonstrate evidence for genetic linkage of C7 deficiency with the major histocompatibility loci. This report represents the first cases of C7 deficiency associated with infectious complications and suggests that bactericidal activity may be important in host defense against bacteremic neisseria infections.


In vivo and in vitro stimulation of nonspecific immunity by the beta-D-p-aminophenyl glycoside of N-acetylmuramyl-L-alanyl-D-isoglutamine and an oligomer prepared by cross-linking with glutaraldehyde. Several biological activities of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP for muramyl dipeptide), a synthetic immunoadjuvant, are inhibited after glycosidation with p-aminophenol. Thus, this glycoside does not induce an increase humoral antibody response in mice when injected in saline, although it retains its stimulatory effect on circulating antibodies and delayed hypersensitivity after administration in a water-in-oil emulsion. The capacity of MDP to stimulate mouse spleen cells is lost, and, moreover, the analogue is unable to increase nonspecific resistance to infection under conditions where MDP is active. After cross-linking of the beta-D-p-aminophenyl glycoside of MDP with glutaraldehyde, several biological activities of MDP are recovered. Moreover, the cross-linked oligomer (molecular weight, approximately 6,000 daltons) is able to stimulate the uptake of thymidine by spleen cells from a strain of mice weakly responsive to MDP and is more active than MDP in protecting mice against bacterial challenge.