[Diaphanoscopy in surgery. Presentation of a cold-light loop for various surgical uses, particularly for the choledochus and retrocavities of the epiploa. Comparison with an earlier system using traditional transillumination]. An account is given of the creation of an autoclavesterilisable, cold-light, transilluminating loop for surgical use following personal endoscopic experience with personally divised instruments, some of which were presented at the Turin Medical and Surgical Meetings held in 1954. It is considered that much valuable can be made of the intense luminous ray, which can be aseptically transfered into the surgery site for direct or transparent viewing. A description is given of a guided, flexible gastroduodenal sound used for obtaining material, insufflation and transillumination, and of a sterilisable, semi-rigid, metal loop used for conventional (hot light) illumination and diaphanoscopy. Lastly, the features of the new (cold-light) optical-fibre metal loop are explained. Its curvature is adaptable for the illumination and transillumination of even deep cavities. Useful employment of the new loop in the surgery of the choledochus and retro-cavities of the epiploa is referred to.


[Pheochromocytoma. Diagnostic aspects and surgical treatment. Apropos of 20 operated cases]. Reference is made to 20 cases of pheochromocytoma operated at the surgical clinic of the University of Padua since 1963. Stress is laid on the importance of modern angiographic techniques in diagnosis and their attendant risks and the main aspects of surgical management are examined. The results show that success depends on careful preoperative localisation, choice of a suitable approach route, and correct technique coupled with suitable intraoperative management.


[Early diagnosis of pulmonary embolism by means of scintigraphy]. The occasions on which lung embolism is likely to occur and proceed with or without initial clinical symptoms are described. Lung scintiscanning technique, complemented by special expedients and personal experience, is explained. It is felt that the method helps in the early detection of suspect or clinically silent forms, as well as in the corroboration or ruling out of a clinical diagnosis as soon as this is possible. Scintiscanning is also of assistance in showing the anatomopathological features and extent of the process. The technique is simple and readily tolerated, even by patients with slight respiratory or circulatory disturbances. On the other hand, it is not competitive with conventional and well-tried angiopneumography.


[Potassium depletion. Glucose intolerance. Senile diabetes. A study of possible pathogenetic relations. 2]. The effects of intake of potassium salts for 21-28 days on the glucose tolerance of 10 elderly subjects with clear diabetes were examined by means of the Tolbutamide test (TT) and the i.v. glucose tolerance test (IVGTT). Improvement in tolerance, to the extent of a reduction in glycaemic levels and better coefficients, was observed in all values of the two tests and in basal glycaemia values, with constantly significant differences at statistical examination. In a group of 4 cases in which Tolbutamide treatment was suspended for the same period, this improvement in the Tolbutamide Test was not observed. With this second confirmation of the initial hypothesis, the pathogenetic significance and biological relevance of potassium depletion in senile diabetes and generally, in the ageing process, are discussed.


[Medical treatment of cholesterol cholelithiasis using chemodeoxycholic acid in man]. The results of a tiral using chenodeoxycholic acid in 400 patients with cholesterol gallstones are reported. The "qualifying points" of such treatment are compared with the literature data in clinical and laboratory terms. 54% of 300 in clinical and laboratory terms. 54% of 300 patients who received less than 12 mg/kg/day achieved dissolution in a mean time of 11 months, while 64% of the remainder (12-15 mg/kg/day) did so in an average of 8 months. Microcalculi proved most sensitive to treatment (65% of positive results). Lithiasis over 5 years standing and over-weight (10% over the ideal figure) were factors that imposed more protracted treatment. Careful selection of candidates was proved important by the results of quarterly liver and intestine performance examinations. These were more extensive and more clearly aimed than those proposed by other workers. They showed that the acid is neither hepato nor enterotoxic. Indeed, no serious side-effects were noted.


[Ionized air respiratory rehabilitation technics]. The use of negative charge ionized air as a technique of respiratory rehabilitation has been examined. After some introductory remarks on the biological action of this climatic factor, literature references are reviewed and personal experience reported. The importance of negative ionization of air is stressed, especially in acute and chronic inflammatory forms of the airways.


[Pickwickian syndrome].

[Pickwickian syndrome]. Respiratory performance tests and EEG and EMG data from two obese patients with ventilatory rhythm disturbances and hypersomnolence are reported. Their insertion within the picture of the Pickwick syndrome is discussed.


Plasma prostaglandins in the normal menstrual cycle. Plasma prostaglandins were studied by radioimmunoassay on alternate days during the menstrual cycle in fourteen normal women. No cyclic patterns were found for A-like prostaglandins using an assay which measured 13,14-dihydro-PGA. Mean subject values of PGA-like prostaglandin ranged from 367 to 904 pg/ml and varied significantly among women. Prostaglandin E determinations showed an upward trend beginning 8 days before the LH peak. PGE subject means varied significantly and ranged from 182 to 362 pg/ml. Prostaglandin F did not exhibit a cyclic pattern. The average concentration of PGF for individual women ranged from 58 to 153 pg/ml, showing significant variance. The physiologic implications of the results are discussed as well as recommendations for the design of future studies.


Management of uterine perforation following elective abortion. Experience is reported with 28 uterine perforations encountered from June 1, 1973, to June 1, 1976, among 20,000 first trimester abortion patients at Reproductive Health Services, St. Louis, Missouri. In order to prevent this complication, one must perform an exacting pelvic examination. The use of a sound is controversial. Dilators should be introduced only a short distance through the internal os, and as much of the products of conception as possible should be aspirated. A sharp curette should be diagnostically. Various questions should be asked before the operator constructs a scheme for managing perforation. The current policy for management used at this clinic is outlined.


Covert bilaterality of mature ovarian teratomas. Over a 21-year period, 213 women with mature teratoma of the ovary were operated on at Parkland Memorial Hospital. Twenty-seven had bilateral tumors. In 22 of these 27 patients, bilateral involvement was evident on clinical examination, and in 5, biopsy of an abnormal but nonteratoid appearing ovary was required to make the diagnosis. Ninety patients with a visually normal opposite ovary had no identifiable tumor in that ovary by investigative incision or incidental excision. Neither incision nor excision of the normal contralateral ovary was performed in 58 cases, and subsequently, one of these women is known to have developed a teratoma in that ovary. We conclude that synchronous covert bilaterality of mature teratomas is not common, and a visually normal contralateral ovary should not routinely be bivalved or wedge biopsied.


The operative evaluation of patients with cervical carcinoma by an extraperitoneal approach. Seventy patients with cervical cancer who were not candidates for primary operative treatment underwent operative evaluation prior to radiation therapy. Thirty-one were explored through a transperitoneal approach and 39 through an extraperitoneal approach. The operative procedure consisted of bilateral pelvic and periaortic lymphadenectomy and exploratory laparotomy, with additional intraperitoneal biopsies taken as indicated by operative findings. Poor correlation was seen between operative findings, lymphangiography, and clinical staging. Radiation therapy was extended to include sites of biopsy proven metastases. The group of patients operated on through a transperitoneal approach experienced a 30% complication rate secondary to small bowel damage following radiation therapy, and 2 patients died as a result of complications. All patients with small bowel complications explored in this manner required surgical correction. The group of patients operated on through an extraperitoneal approach had a 2.5% morbidity secondary to small bowel complications, and there were not deaths or serious complications in these patients. No patients explored in this manner required subsequent operation for complications following radiation therapy.


Complications following parametrial radiogold treatment for cervical carcinoma. Between January 1950 and March 1965, 382 patients with carcinoma of the uterine cervix were treated with parametrial radiogold injections. One hundred and ninety-two patients are known to have survived 5 or more years after the treatment without evidence of recurrence. Major complications with significant morbidity requiring hospitalization or additional surgery was observed in 9.4% of the patients. Parametrial radiogold injection is associated with a high incidence of major lower urinary tract complications, including an increased incidence of ureteral obstruction as a result of radiation fibrosis, Heterogenous distribution of radioactive material with localized areas of heavy irradiation is probably responsible for the development of late major complications.


Treatment of vulvovaginal candidiasis in pregnancy. A comparative study. A carefully controlled comparative study showed miconazole nitrate 2% vaginal cream (Monistat) to be a highly effective agent in the treatment of vaginal candidiasis in pregnant subjects. Miconazole nitrate was significantly more effective than nystatin (Mycostatin) in the treatment of vaginal candidiasis in all three trimesters of pregnancy, and also more effective regardless of whether the candidal infection was primary or recurrent. Observations relating to the safety of this therapy during pregnancy were made and discussed.


Amniotic fluid lecithin/sphingomyelin ratio changes related to centrifugal force. Lecithin/sphingomyelin ratio (L/S ratio) in amniotic fluid has gained wide clinical acceptance as an index of fetal lung maturity. We determined L/S ratios of amniotic fluids centrifuged at various "g-forces." Our studies demonstrate that the L/S ratio value is highly dependent on the g-force used to prepare the fluid. We recommend standardization of the g-force, time, and temperature used in preparation of the amniotic fluid for L/S ratio determination.


The significance of fetal heart rate reactivity with a positive oxytocin challenge test. This study reviews 27 patients with positive OCTs who were subsequently allowed a trial of directly monitored labor. Of these, 19 patients (70%) developed FHR signs of fetal distress and 8 (30%) tolerated labor without late decelerations. These patients were evaluated for signs of fetal reactivity (acceleration of the FHR associated with fetal movement of contractions) during the OCT. Those with a reactive pattern during the OCT (15 patients) uniformly had a good fetal outcome (unless there was birth trauma or premature delivery), but 8 of these 15 patients showed fetal distress during monitored labor. If the positive OCT was associated with a nonreactive baseline FHR recording, a trial of labor uniformly resulted in FHR signs of fetal distress. It is therefore concluded that a patient with a nonreactive positive OCT is unlikely to tolerate subsequent labor without fetal distress.


Calcium, magnesium, phosphorus, and parathyroid hormone interrelationships in pregnancy and newborn infants. The ability to measure directly human parathyroid hormone (hPTH) and ionized calcium (Ca++) is of fundamental importance in understanding their interrelation in pregnancy and the newborn. hPTH and Ca++ progressively increase throughout pregnancy. Since Ca++ is the direct determinant of hPTH levels, a different "set point" appears to be operative throughout pregnancy. The newborn infant, on the other hand, has higher serum Ca++ levels than its mother, and the infant's plasma hPTH is suppressed to undetectable or low levels. Ca++, total serum Ca, magnesium, and phosphorus are all significantly elevated in the serum of the mother at delivery. An active transport mechanism of all these minerals appears to be operative and lowers the maternal serum levels at the termination of labor in relation to serum levels in the third trimester of pregnancy.


The effect of Imuran on implantation and early embryonic development in rats. Pregnant rats were injected daily with 2, 4, and 20 mg/kg of Imuran from the first day of gestation until sacrificed on Days 6-12. Gravid uteri, as well as maternal organs, were removed and examined histologically. According to the histologic findings, the treatment with the high dose of 20 mg/kg/day Imuran induced injuries to the blastocyst. Starting from Day 8, the trophoblastic layer lost its continuity and maternal blood invaded into the blastocystic cavity resulting in destruction of embryonic tissues. This degeneration progressed until evident resorption on Day 12. Smaller doses, such as 2 or 4 mg/kg of Imuran, did not result in early trophoblastic damage. The effect seemed to be the result of the antimetabolic effect of Imuran acting on the proliferating trophoblast through the maternal blood.


Management of postoperative introital and vaginal stenosis. Five patients with symptomatic postoperative introital or vaginal stenosis were evaluated and treated. In each case simple operative correction, utilizing basic plastic surgery principles, was successful. The five operative techniques as used alone and in combination are described. Though postoperative stenosis of the vagina and/or introitus is relatively uncommon, the resulting disability is such that every gynecologic surgeon should be familiar with the problem and solution. In most cases simple surgical correction can be successful if the surgeon is familiar with basic techniques and principles.


Relation between optical density at 650 nm and L/S ratios. A simple and rapid test that correlates with L/S ratios has been developed. By centrifuging fresh, unfrozen amniotic fluids at 200g for 10 minutes and measuring the optical density at at 650 nm, correlation with L/S ratios is obtained. Optical density readings of 0.15 or greater correlate 100% with L/S ratios of 2.0 or greater. Optical readings below 0.15 correlate 94% with L/S ratios below 2.0.


Adenocarcinoma of the endometrium with psammoma bodies. Two patients with endometrial carcinoma containing psammoma bodies are presented. The necessity of distinguishing this neoplasm from an ovarian carcinoma is stressed. The rarity of this finding and its histogenesis are discussed, and the literature on the subject is reviewed.


Papular (erosive) herpes genitalis. A clinical variant in sarcoid and pregnancy. A unique papular (erosive) variant of herpes genitalis is described in a patient with sarcoid and in 1 who was pregnant. The occurrence of this unique expression of herpes infection in two conditions associated with immunologic changes seems more than incidental. It is suggested that patients presenting with papular (erosive) herpes genitalis be studied for underlying immune deficiency.


Successful management of pregnancy-induced pancytopenia. The 46th case of known pregnancy-induced pancytopenia is reported. Pregnancy may play an etiologic role in this rare condition, but the specific mechanism is unknown. Maternal mortality is 63%, and fetal and neonatal wastage is 46%. The patient reported is a 24-year-old Oriental woman who delivered a healthy female infant. Her survival is attributed to conservative management with carefully timed packed cell and platelet transfusions.


Reconstruction of radical mastoid cavities: methods and results. The radical mastoid cavity can be troublesome and odoriferous, may require frequent visits to an otologist, and may interfere with swimming and showering. Three procedures can be used to reconstruct the radical mastoid cavity. Soft tissue obliteration with autograft bone paste is the most versatile and commonly used technique. Reconstruction with homograft external auditory canal bone is useful for extremely large mastoid cavities that are free of infection. Use of these techniques in 35 patients since 1969 has resulted in dry, trouble free ears and improved hearing when reconstruction of the ossicular chain was performed. Use of this technique has helped patients with radical mastoid cavities to return to a normal active life style.


Homograft tympanoplasty techniques and results for restoration of hearing. The use of a homograft tympanic membrane with and without attached ossicles, staging the operation, and the use of sculptured homograft or autograft ossicles have improved the results in tympanoplasty. The indications and techniques of homograft tympanoplasty are described, and the results in 99 primary cases and 11 cases with repair of a mastoid cavity are given. The overall graft success rate was 86 per cent. In patients with an intact ossicular chain, the conductive loss was reduced to less than 20 dB. in 88 per cent. A hearing loss less than 20 dB. was obtained in 68 per cent with an intact stapes, in 77 per cent when the stapes superstructure was absent, and in 79 per cent in stapedectomy done at a second stage. The use of homograft material has provided the means for significantly improving the results in our patients who require tympanoplasty.


Hearing and anatomical results with homograft tympanoplasty. Homograft tympanic membranes and ossicles have been found to be a valuable asset in tympanoplasty surgery. The homograft tympanic membrane has been used in conjunction with a canal skin graft with a graft take rate of 94 per cent. Anatomical results have been gratifying in that most patients are totally rehabilitated and may swim or shower without restrictions. The homograft incus has been sculptured into prostheses to reconstruct the sound conduction mechanism, both at the initial procedure and in revision cases to improve the hearing.


The establishment of an ear bank.

The establishment of an ear bank. Tympanic membrane and ossicle homografts have been successfully used in reconstructive ear surgery during the last 12 years. Ear banks have proven to be practical to insure a regular supply of high quality homografts for the otologic surgeon. The most important aspects in establishing an ear bank include the procurement of temporal bone cores, the establishment of homograft dissection technique, and attention to preservation and distribution procedures and the problems of maintenance.


Attempted suicide in patients admitted to hospital in Wigan and Leigh Borough, England. An investigation of various variables in 100 para-suicide patients admitted to Wigan and Leigh Group of Hospitals was carried out. The subject's age, sex, religion, social class, type of residence, previous treatment received, etc., were examined in detail.


In vivo and in vitro availability of commercial vitamin C tablets. In vitro release of vitamin C from commercial tablets of three different manufacturers was measured by the Levy beaker, a modified USP basket and Magnetic Basket techniques and this was correlated with urinary excretion of the drug from normal, healthy, human males of 23 to 25 years of age weighing 50-72 Kg. Results showed that there was dissolution variability between the different brands of vitamin C tablets as well as between the in vitro dissolution methods used. There was also an inverse correlation between the time of in vitro release and the percent vitamin C excreted at the end of 2 hours. However, at the end of 24 hours the most rapidly dissolving tablets in vitro indicated only 66 percent excretion of the vitamin C as compared with nearly 83 percent for the slow dissolving types. It is concluded that to determine the total drug from a particular formulation, only disintegration and/or dissolution is not a good measure for an unstable and relatively rapid dissolving substance such as vitamin C. It is further suggested that perhaps if unstable rapid-dissolving substances were made more slowly released by formulation, a greater quantity of the drug would be physiologically avaiable.


Primary squamous cell carcinoma of the endometrium report of a case and review of the literature. A case of primary pure squamous cell carcinoma of the endometrium in a 50-year-old woman is reported. There was deep myometrial and para-cervical invasion. There is no evidence of metastases 2 years after total hysterectomy and salpingo-oophorectomy and radiation therapy. The patient is probably the youngest suffering from such a tumor. A detailed review of the literature has been carried out.


Concurrent mapping of brain sites for sensitivity to the direct application of morphine and focal electrical stimulation in the production of antinociception in the rat. The effect of morphine microinjection (5 microgram/0.5 microliter) and focal electrical stimulation on the animal's response to radiant heat and noxious pinch was studied concurrently at 117 brain loci extending from the medial thalamus caudally to the periaqueductal gray area (PAG). Three populations of brain sites were discernible based on their responsiveness to focal electrical stimulation and morphine microinjection in the production of antinociception: (a) sites which support stimulation-produced analgesia (SPA, n = 24), (b) sites which were sensitive to the direct application of morphine (n = 8), (c) sites responsive to both manipulations (n = 8). With a few exceptions, all morphine sensitive sites were located within the anatomical boundaries of the PAG while sites supporting SPA were located not only within the PAG but also in the brain regions peripheral to this structure. Sites responsive to both manipulations were generally distributed throughout thf lateral aspect of the posteroventral PAG. Stimulation strength-effect curves for sites subserving SPA were also obtained. No differences were discovered between curves obtained from morphine-sensitive and -insensitive brain loci.


Response to cold pressor pain and to acupuncture analgesia in Oriental and Occidental subjects. On a no treatment trial, a group of 24 oriental subjects rated cold pressor pain as significantly more painful and distressing than did a group of 24 occidental subjects. For half of the Orientals and half of the Occidentals, a second trial was conducted after acupuncture analgesia had been induced. The remaining 12 Orientals and 12 Occidentals served as no treatment controls on trial 2. Regardless of racial group, there was no difference between the pain of those experimental subjects who received acupuncture and the pain of those controls who did not. As they had on trial 1, Orientals reported significantly more pain and distress in response to ice water on trial 2. It is concluded that: (1) if acupuncture does work better for the Chinese than for other racial groups, the likely cause is a more refined patient selection procedure rather than an inherent difference in response to acupuncture; (2) evidence does not support the stereotyped view of Orientals as stoical in the face of physical pain.


Pain relief during delivery by transcutaneous electrical nerve stimulation. The degree of pain alleviation achieved by transcutaneous electrical nerve stimulation (TNS) during delivery has been evaluated. The usual technique of TNS was modified to suit the requirements of pain relief during delivery. Two pairs of electrodes were taped on the parturient's back at levels TH10--L1 and S2--S4. These segments correspond to the pathway of pain afferents into the spinal cord during the first and second stages, respectively. Stimulation was delivered by a two-channel generator producing biphasic pulses which were variable in frequency and amplitude. A low-intensity stimulation was given continuously and a high-intensity stimulation could be initiated by the parturient herself whenever pain increased. Stimulation was provided via the thoracic electrodes throughout the delivery, whereas sacral stimulation was added from the later part of the first stage. No complications with respect to mother or child have occurred. One hundred and forty-seven women have been treated, 65 (44%) of whom considered the pain relief by TNS to be good to very good, 65 (44%) experienced moderate effect, while 17 (12%) women considered that TNS was without effect. In view of the relatively good results and since no complications have occurred, we consider the method recommendable as a primary pain relieving measure to which conventional methods can be added according to need.


Aversive behavior therapy for chronic stomach pain: a case study. A combined behavioral-psychodynamic treatment for severe, chronic stomach pain has been presented. In the case discussed, neither psychotherapy nor behavior therapy alone was successful in dealing with the patient's somatized depression. Aversive conditioning was credited with eliminating verbal report of pain and subjective sensation of chronic gastric pain. Simultaneous with the reduction in pain, however, the patient became increasingly depressed. Analytically oriented psychotherapy was instrumental in resolving the depression.


Translation in a reticulocyte cell-free system of RNA isolated from blood and culture forms of Trypanosoma brucei. RNA with messenger activity has been extracted from both blood and culture (insect mid-gut) forms of Trypanosoma brucei and translated in a reticulocyte cell-free system. The products of this cell-free system have been compared, and many common polypeptides demonstrated. A major polypeptide of 58000--65000 molecular weight was made when both blood and culture form RNA was added to the cell-free system. Antiserum raised against purified variant antigen from a cloned variant (MIAG 099) was used to detect specific products of this system. A major polypeptide of approximately 58000-65000 molecular weight was precipitated when the homologous trypanosome (MIAG 099) blood form RNA was used in the cell-free system. No such polypeptide was precipitated when RNA from a heterologous strain culture or blood form was used in the system. Competition experiments, in which excess purified variant antigen was addded after incubation but before addition of specific antiserum, confirmed that the polypeptide of 58000--65000 molecular weight is the variant antigen.


The anticoccidial effects of amprolium, dinitolmide and monensin against Eimeria maxima, E, brunetti and E. acervulina with particular reference to oocyst sporulation. Chicks infected with the Weybridge strains of Eimeria maxima and E. acervulina were not protected by the normal levels of amprolium, but the sporulation of the oocysts was inhibited. With higher drug concentrations, fewer oocysts were produced. E brunetti was not so markedly affected, although oocyst sporulation was reduced by the higher dosage levels. The effects were not enhanced by the inclusion of ethopabate. With dinitolmide the phenomenon was not so marked, although oocysts of E. maxima and E. acervulina were reduced in numbers by the normal drug concentration and sporulation was reduced when this level was increased. Much higher drug levels were required to obtain these effects with E. brunetti. Monensin at 120 ppm affected neither oocyst numbers nor their sporulation in any of the species tested. The significance of the effects of anticoccidial drugs on gametogony and sporogony is discussed.


Studies on the growth, chemotherapy and enzyme variation of Eimeria acervulina var. diminuta and E. acervulina var. mivati. Eimeria acervulina var. diminuta was serially passaged 12 times in chicken embryos, but growth in cultured chick kidney cells was limited to 2 generations of schizonts. After 7 embryo passages the sensitivities of E. acervulina var. diminuta and an embryo-adapted strain of E. acervulina var. mivati to the anticoccidial drugs amprolium, methyl benzyquate, robenidine and sulphaquinoxaline were compared. Both parasites were sensitive to all the anticoccidials but E. acervulina var. diminuta was more sensitive to sulphaquinoxaline and amprolium. The chicken-maintained strain of E. acervulina var. diminuta was extremely sensitive to clopidol, sulphaquinoxaline and decoquinate. Electrophoretic analyses of several enzymes from E. acervulina var. diminuta revealed enzyme profiles with similarities and differences to the embryo-adapted strain of E. acervulina var. mivati.


Strain variations within Eimeria meleagrimitis from the turkey. During the course of a field study of coccidiosis in turkeys, Eimeria oocysts were found which had much smaller dimensions that any previously recorded isolate from the turkey. These oocysts were purified by single oocyst infection of a turkey. The first oocysts (mean dimensions 16-15 X 14-75 micrometer) were recovered 103 h later. Inoculation of between 0-5 and 2-5 X 10(5) oocysts of this isolate caused severe effects on body weight gain. Cross-immunity studies showed the parasite to be a strain of E. meleagrimitis. Electrophoretic analyses of two enzymes showed that the strain could be differentiated from another strain of E. meleagrimitis (Weybridge strain B). The results show that strain variation occurs within the species E. meleagrimitis and extreme caution should be used in identifying species of Eimeria from the turkey by the oocyst characters.


Vaccination of lambs against infection with Taenia ovis using antigens collected during short-term in vitro incubation of activated T. ovis oncospheres. Activated oncospheres of Taenia ovis were incubated for 24 h or 48 h at 37-5 degress C in Medium 858 alone or in Medium 858 enriched with 20% lamb serum or foetal calf serum. Antigens contained in the supernatant medium from these incubations were concentrated, emulsified in Freund's incomplete adjuvant and injected intramuscularly into lambs. These lambs developed a very high level of immunity to subsequent challenge infection with T. ovis eggs.


Intra-erythrocytic death of the parasite in mice recovering from infection with Babesia microti. As mice recover from infection with Babesia microti, abnormal forms of the parasite are present in some red cells. These forms are non-infective, indistinguishable by light microscopy from those present after treatment with amicarbalide, a babesicidal drug, and persist in splenectomized mice. Electron microscopy confirmed that these abnormal forms are degenerating intra-erythrocytic parasites. In the absence of evidence for death of B. microti elsewhere in the body, it appears that infections of mice with this parasite are normally terminated by their death within circulating red cells. This has important implications for the mechanism of immunity to both this parasite and those Plasmodium spp. with which it cross-protects in this host.


The effect of the suckling stimulus on the migration of Strongyloides ratti in lactating rats. The number of adult Strongyloides ratti which developed in the guts of lactating rats after subcutaneous injection of 4000 L3 on day 18--20 post partum was taken to be a measure of the relative importance of alternative larval routes. When injection was carried out at different times before and after weaning, larvae were diverted from a route bypassing the gut in nursing mothers to one leading to the gut ("migration reversal") in mothers without young in a period of less than 10 h. Migration reversal was mostly completed in lactating females injected at the time of weaning when compared with nulliparous controls. A stimulus-sensitive period shortly after injection, predicted from these dynamics, was demonstrated. Worms injected into lactating females 10 h after removal from their pups showed complete migration reversal. In similarly treated rats, given 1 h suckling 3 h after injection, migration reversal was practically abolished. These inter-relationships, in conjunction with earlier findings, are used to deduce the possible humoral mechanisms involved and to develop a working hypothesis to account for larval orientation based on features of the mammalian pulmonary microvasculature.


Hymenolepis microstoma: a change in susceptibility to resistance with increasing age of the parasite. Hymenolepis microstoma from secondary infections in mice were found to grow initially more slowly than H. microstoma from primary infections. Eventually a similar rate of growth was attained by both kinds of worm. After transplantation, young worms (less than or equal to 4 days old) grew more slowly in previously infected than in naive mice. In contrast, 10-day-old worms grew equally well in naive or resistant mice. The administration of cortisone to mice during a secondary infection of H. microstoma inhibited the stunting of growth in young worms which were able to grow as well as those in a primary infection. The effects of the cortisone persisted for less than 4 days. Worms in a secondary infection given 4 days after cortisone treatment were stunted in growth. These experiments suggest that the susceptibility of the worms to the resistance of the mouse applies to the first 4 days within the host. The loss or reduction of this susceptibility might be associated with the worm's entry into the bile duct which occurs 3--4 days after infection.


Patency and transmission of Filaroides hirthi infection. Filaroides hirthi lungworm infection was diagnosed by the recovery of 1st-stage larvae from the faeces of dogs with heavy, artificially induced infections using zinc sulphate flotation. Diagnosis of low-grade natural infections was infrequently achieved. Zinc sulphate flotation was demonstrated to be about 100 times as efficient as the Baermann technique in concentrating F. hirthi larvae from dog faeces. Larvae recovered from faeces proved to be infective when fed to a pup and it was concluded that F. hirthi infection can be transmitted directly and immediately by fresh faecal contamination. Mongrel dogs of diverse ancestry were readily infected by feeding 1st-stage larvae from lung tissue. Thus, F. hirthi infection was shown not to be limited to the Beagle breed by biological restrictions. The observations that 1st-stage larvae pass through the alimentary tract on their way out of the body and that larvae are found in the mesenteric lymph nodes long after a single exposure to infection support the hypothesis that there is an autogenous re-infection of the host by a proportion of these larvae.


Congenital deformities.

Congenital deformities. Forty years ago Denis Browne wrote that the medical world was ignoring an important distinction among birth defects. There were, he said, a large group of abnormalities caused not by genetic errors or teratogens but simply by fetal constraint. These abnormalities, if recognized early, could be readily ameliorated with simple, conservative forms of therapy. Today the full range and frequency of deformations are still not well appreciated and yet the recognition of these deformities may be more important than ever. The public is becoming increasingly aware of environmental hazards and genetic risks to their unborn children. They know of the  difficult problems faced by families when malformed children are born. The physician who can rapidly and accurately diagnose deformities treats a good deal more than the problems of aberrant fetal molding.


Origin and mechanism of postnatal deformities. The child's skeleton must be thought of as a dynamic organ-formed, moved, and remodeled but unchanged. However, if the normal balance of the skeleton's environment is disturbed, the unchanging form also becomes disturbed and deformity occurs. This disruption of the environment may be mechanical imbalance, vascular insufficiency, metabolic abnormality, or external insult. The manner in which the skeleton responds depends on the disturbing force and the affected area.


Radiographs.

Radiographs. Physicians performing radiology for children should utilize modern equipment, expose children to the least amount of radiation possible, and avoid unnecessary examinations. Those interpreting radiographs must be familiar with the wide range of normal variations of the skeleton and/or be prepared to refer to texts and atlases dealing with these. Careful examination of soft tissues greatly increases the accuracy of diagnostic radiology in the search for trauma and infection.


Radionuclide bone imaging in pediatrics. Radionuclide imaging provides a functional as well as anatomic evaluation of bone and is particularly valuable in diagnosis, staging, and management of oncologic disorders, in differentiation of inflammatory conditions and trauma, and in hypovascular disorders of bone. The practitioner should be aware of those areas in which bone imaging is clinically effective for patient care. Radionuclide bone imaging is efficacious, delivers minimal radiation, and offers a functional method of evaluation for children with skeletal disorders.


Orthopedic screening: especially congenital dislocation of the hip and spinal deformity. Effective techniques exist for the early detection of congenital dislocation of the hip and of scoliosis, as well as related spinal deformities, allowing correction and prevention of serious permanent deformities. Future developments seem likely to make prenatal detection of spina bifida cystica possible and also may point the way toward means of decreasing the incidence of disabling low back pain and of osteoarthritis of the major joints of the lower extremity.


Leg aches.

Leg aches. In the investigation of children with leg aches, it is essential to identify those with demonstrable underlying organic diseases. Growing pains is a poorly named, nebulous entity that can be diagnosed only by exclusion. The greatest diagnostic error is to make a diagnosis of growing pains while overlooking some serious underlying condition.


Foot pain in children.

Foot pain in children. A general approach to the child with foot pain has been described. In that the pediatrician is so often the recipient of parent's questions about children's shoes, it is well for him to be aware of problems relating to poorly fitting shoes, probably the most common source of complaints of foot pain in children. With a systematic approach, the pediatrician is very capable of managing the majority of such complaints.


Sagittal diameter measurements of the bony cervical spinal canal in children. Radiological measurements of the sagittal diameter of the bony cervical spinal canal were performed on 120 children, aged 3 to14 years old. For the age groups 3 to 6, 7 to 10 and 11 to 14 years the appropriate mean values were calculated with standard deviations. In addition the relation between body height and width of the spinal canal was investigated. The values show a continuous increase with advancing years and increasing body height. In all age groups the sagittal diameter decreases slightly from the foramen magnum to C.3 and then remains nearly constant. There are no statistically significant differences between boys and girls. The "normal values" obtained facilitate the detection of pathological cases where there may be widening or narrowing of the cervical spinal canal.


Total anomalous pulmonary venous connection. Report of ten cases and review of the literature. Ten cases of total anomalous pulmonary venous connection, all presenting at or below the age of eight weeks, are presented: three below the diaphragm, two to the coronary sinus, one to the right atrium, three to the left vertical vein, and one to the right superior vena cava. Six patients had other cardiac anomalies, and surgical mortality represented 75%. A review of the subject is presented.


Detergent enema: a cause of caustic colitis. A 5-year-old boy developed acute colitis followed by stricture formation as a result of a detergent enema. The acute phase of the caustic induced colitis was reproduced in the dog and the rat using full strength and diluted detergent enemas. The severity of the experimental colitis was shown to be directly related to the concentration of the detergent.


Indications for pneumoperitoneum in the diagnosis of congenital anomalies in the umbilical region. Thirty pneumoperitoneograms were performed postmortem and 5 were performed for diagnosis: the technique itself, the radiological anatomy of the umbilical region, and the usefulness of the procedure in diagnosis are discussed. Pneumoperitoneum may be indicated in the investigation of a bleeding Meckel's diverticulum, in the exclusion or confirmation of remnants of the omphalomesenteric duct, in chronically moist lesions of the umbilicus resistant to symptomatic treatment, in suspected cases of non-communicating urachal cysts which cannot be diagnosed by cystogram, and in the differential diagnosis of abdominal tumours related to the umbilical region.


Leri's melorheostosis: three pediatric cases and a review of the literature. Three pediatric cases of melorheostosis are described. Growth disorders of the limbs are often the first signs in children. The radiological appearance consists of long tracks of increased cortical radiodensity in the long bones and of small dense islets in the epiphyses.


Acute epitrochlear lymphadenitis.

Acute epitrochlear lymphadenitis. This paper summarizes the clinical and roentgenographic findings in 15 children with acute suppurative infection of the epitrochlear lymph nodes.


Is the first urinary infection in childhood a definite indication for radiological examination? The need for X-ray investigations of the urinary tract at the time of the first proven urinary infection, even in older girls, is stressed. This policy is the best way to detect chronic pyelonephritis and congenital anomalies of the urinary tract and provide timely and appropriate treatment. These conclusions are supported by personal experience (see case description), and the incidence of congenital anomalies encountered during an 11 year period in our children's hospital. There were 957 concecutive cases with X-ray studies of the urinary tract (IVP and MCU). A considerable proportion (30%) were older children (4-12 years) having supravesical obstruction defined when the X-ray studies were performed at the first urinary infection. The proportion of abnormalities rose to 66% when the investigations were done after recurrent infections, which may contribute to the development and progression of disease.


Application of aortography and ultrasound in evaluation of renal agenesis. Ultrasound followed by aortography, if necessary, has been a useful approach in the diagnosis of suspected renal agenesis.


Renal vein thrombosis: a cause of intrarenal calcification in the newborn. The calcification which may follow renal vein thrombosis (RVT) has a virtually diagnostic radiographic pattern. Previous examples have been noted mainly in follow-up examinations of infants with a history of neonatal RVT. The case reported herein, with pathologic confirmation, illustrates that such calcification may be present even on the first day of life as a result of RVT occurring in utero.


Congenital calcified thrombosis of inferior vena cava, bilateral renal veins and left spermatic vein. An infant with severe congenital calcified thrombosis in the inferior vena cava, bilateral renal veins and left spermatic vein is presented. Five previously published cases and pertinent points concerning this rare occurence are discussed. The etiology of this calcified thrombosis remained unknown.


Pierre Robin syndrome with hyperphalangism-clinodactylysm of the index finger: a possible new palato-digital syndrome. A nine day old boy who had the Pierre Robin syndrome also had an unusual associated hand malformation consisting of bilateral clinodactyly of the index finger. A supernumerary phalanx was inserted between the second metacarpal and the proximal phalanx of both index fingers with a radial deviation of the same phalanx. The same hand malformation has been previously described in three patients who had either the Pierre Robin syndrome or isolated cleft palate. On the basis of ours and the three previous cases, the existence of a new palato-digital syndrome is suggested.


Cavitating lesions in a cold agglutinin positive pneumonia. Cavitating lesions are considered a rare presentation for cold agglutinin positive pneumonia. This paper describes a case of cold agglutinin positive pneumonia which presented as a multilobar, cavitating bronchopneumonia.


Congenital syphilitic osteitis of scapulae and ribs. A newborn with congenital syphilis presented radiographically with a lack of ossification of the medial portions of several ribs and massive sclerosis and decalcification of scapulae. The uniqueness of syphilitic scapular and rib involvement is discussed. The infant also went on to develop skin lesions which appeared following penicillin therapy and also developed an extrahepatic biliary atresia.


[Tumour-induced precocious puberty. Discussion of the indications for neurosurgery (author's transl)]. The tumour aetiology of precocious puberty is sometimes clinically evident when accompanied by visual disturbances or by raised intracranial pressure. It may be suspected in the presence of accelerated puberty but should also be feared in cases of apparently idiopathic precocious puberty. In the 13 cases studied, the tumour was studied in the posterior hypothalamus. Ten children underwent surgery (with additional radiotherapy in two cases). Two children died, the follow-up varying at present between 2 and 12 years. Amongst the various tumours, the hamartoma has a special nature by virtue of slow or absence of increase in tumour size. When the clinical and radiological signs suggest this type of tumour, abstention from surgery with close observation of the size of the tumour and medical slowing of puberty is advised.


[Hereditary C2 deficiency with systemic lupus erythematosus: clinical and immunologic studies in a family (author's transl)]. A case of systemic lupus erythematosus associated with an homozygous deficiency in the second fraction of complement is reported and compared to previous reports of the literature. The high incidence of infections in these patients is outlined. The defective gene in this family was associated with the HLA A10B18 haplotype and the propositus was homozygous at the HLA-D locus. Familial study allowed the detection of 3 heterozygous individuals two of them being symptomatic (vascular purpura, high incidence of bacterial infections).


[Effects of hepato-biliary diseases on drug metabolism (author's transl)]. Drug metabolism may be impaired in patients with hepato-biliary diseases. Hepatocellular failure may decrease the rate of drug biotransformation; cholestasis may decrease 1) the absorption of lipid soluble drugs, 2) the rate of drug biotransformation, and 3) the biliary excretion of drugs. Activity and/or toxicity are modified variously as either the drug or a metabolite of it is the active and/or toxic compound. Although there is an obvious need for an adapted posology in patients with liver diseases, only suggestions can be drawn from presently limited data.


Distribution of H1 histone in chromatin digested by micrococcal nuclease. The relative amount of H1 histone associated with isolated nucleosomes from calf thymus was determined as a function of the extent of DNA digestion by micrococcal nuclease. Generally the amount of H1 histone associated with mononucleosomes decreases with increasing digestion until 60% of the original H1 remains associated with DNA 150 base pirs or less in size. Coincidentally, H1 histone increases relative to the other histones in aggregated material that sediments through sucrose gradients to form a pellet. However, the level of H1 histone remains at control values for oligonucleosomes (dimer to hexamer) over the 30% digestion range studied. An increase in ionic strength to 0.3 M NaCl in the density gradient reveals a different pattern of H1 binding, whereby the amount of H1 reflects the average size of the DNA fragments with which it is associated. Although there is significant binding to nucleosomes per se, it appears that the major ionic involvement of H1 is with internucleosomal spacer DNA.


A simple method for the preparation of [beta-32P]purine nucleoside triphosphase. A rapid, simple and inexpensive procedure is described for the preparation of purine ribo-and deoxyribonucleoside triphosphates specifically and highly radiolabeled with [32P]phosphate in the beta position. The method involves two successive enzymatic reactions: conversion of donor [gamma-32P]ATP in the presence of an excess of acceptor 5'-mononucleotide to the 5'-diphosphates by myokinase or guanosine 5'-monophosphate kinase followed by phosphorylation with pyruvate kinase to yield 5'-triphosphates.


5' Caps in hnRNA: absence of m32,2,7G and size distribution of capped molecules. In HeLa cells the "small nuclear" RNA has a cap II 5' structure (8)-- m32,2,7G(5') pppXmpYmp-- where X and Y are 2'0 methylated adenosine and uridine. In contrast hnRNA contains only cap I structures were the 2'0 methylated residue may be any base as was earlier reported for cytoplasmic mRNA (8,9,11). With a clear distinction between the source of these two caps an analysis of the size distribution of capped hnRNA could be performed which revealed over 65% of the capped hnRNA molecules were larger than cytoplasmic mRNA.


Prepartation of soluble chromatin and specific chromatin fractions with restriction nucleases. By digestion of rat liver nuclei with EndoR HaeIII, EndoR EcoRI, and EndoR Bam and subsequent lysis of the nuclei approx. 90%, 40%, and 45%, respectively, of the chromatin were solubilized. The plateau values of solubilization are in agreement with a model in which the chromatin strands are crosslinked and/or attached to a supporting structure. The distribution of DNA lengths in the soluble and insoluble chromatin fractions were determined. According to digestion experiments with restriction nucleases rat liver DNA contains highly repetitive sequences, some of which are arranged in tandem repeats of 95 and 380 nucleotide pairs, respectively. With EndoR EcoRI chromatin containing the repetitive RNA was preferentially solubilized and, by subsequent sucrose gradient centrifugation, purified to about 90%. The useful properties of chromatin prepared by the specific action of restriction nucleases are discussed.


Use of specific endonuclease cleavage in RNA sequencing-an enzymic method for distinguishing between cytidine and uridine residues. The extracellular ribonuclease I of the common slime mold physarum polycephalum (RNase Phy1), which has recently been purified to homogeneity, has been used to distinguish between C and U residues in 3'-end-labeled oligoribonucleotides. As shown by Bargetzi and coworkers, this enzyme exhibits strong cleavage preference for U-N over C-N and N-C over N-U bonds. In the present paper, conditions are being detailed, which enable one to deduce the sequences of rather large, pyrimidine-rich, terminally labeled oligonucleotides by partial digestion with RNases U2, A, and Phy1, followed by resolution of the cleavage products by size. The techniques described in this and a previous communication provide a direct means for identifying A, G, C, and U residues in end-labeled polyribonucleotides.


Metabolic heterogeneity of nuclear poly (A)-containing RNA in mouse liver. The analysis by the approach to equilibrium labeling method has shown that the poly(A)+ fraction of liver hnRNA is not a uniform class of molecules, but is comprised of two distinct subclasses with half-lives of 5 and 60 min, while the poly(A)- hnRNA was metabolically homogeneous and turned over with a rather uniform half-life of 30 min. The results suggest that (a) poly(A) synthesis and addition is not limiting for the rate of hnRNA processing, and (b) there is a correlation between the kinetics of mRNA appearance in the cytoplasm and kinetic behavior of their possible nuclear precursors.


DNA chain flexibility and the structure of chromatin nu-bodies. The persistence length of high-molecular-weight, monodisperse-bihelical DNA has been evaluated from low-shear flow birefingence and viscosity data at several temperatures in 2.0 M Nacl neutral pH buffer. At these solvent conditions, both the DNA and histone components of chromatin nu-bodies have structural features similar to those in the intact nucleohistone complex at low ionic strength. The theory of Landau and Lifshitz is used to relate the experimental result to the thermodynamic functions for bending 140 nucleotide pairs of DNA into a plausible model structure: per nu-body, delta Gb=43.8 +/- 5.3 kcal/mole, delta Hb= 45.7 +/- 3.7 kcal/mole, and delta Sb = 6.2 +/- 12.4 entropy units. This bending free energy is comparable to or less than that estimated to be required for a kinked DNA configuration and appears to be well within the range of estimated electrostatic free energies available from DNA-histone interactions in a nu-body assembly.


Renaturation kinetics and thermal stability of DNA in aqueous solutions of formamide and urea. This paper reports the results of a systematic study of the effects of formamide and urea on the thermal stability and renaturation kinetics of DNA. Increasing concentrations of urea in the range 0 to 8 molar lower the Tm by 2.25 degrees C per molar, and decreases the renaturation rate by approximately 8 percent per molar. Increasing concentrations of formamide in the range from 0 to 50 percent lowers the Tm by 0.60 degrees C per percent formamide for sodium chloride concentrations ranging from 0.035M to 0.88M. At higher salt concentrations the dependence of Tm on percent formamide was found to be slightly greater. Increasing formamide concentration decreases the renaturation rate linearly by 1.1% per percent formamide such that the optimal rate in 50% formamide is 0.45 the optimal rate in an identical solution with no formamide. The effects of urea and formamide on the renaturation rates of DNA are explained by consideration of the viscosities of the solutions at the renaturation temperatures.


Highly efficient translation of messenger RNA in cell-free extracts prepared from L-cells. Micrococcal nuclease was used to eliminate endogenous protein synthesis in extracts prepared from L cells. The nuclease can be inhibited subsequently with 2'-deoxythymidine-3', 5'-diphosphate. Nuclease-treated extracts primed with exogenous reovirus mRNA, synthesized full length polypeptides with linear kinetics for almost two hours leading to stimulation of the order of 10(4) times over endogenous background. On the average, between 40 and 50 molecules of polypeptide were synthesized per molecule of mRNA.


DNA associated with nucleosomes in plants. 50 to 55% of tobacco and barley nuclear DNA is accessible to micrococcal endonuclease digestion. The DNA fragments resulting from a mild endonuclease treatment are multiples of a basic unit of 194 +/- 6 base pairs in tobacco and 195 +/- 6 base pairs in barley. After extensive digestion, a DNA fragment of approximately 140 base pairs is predominant. Hence the "extra-core" or "linker"-DNA is 55 base pairs long. Other fragments having 158 and less than 140 base pairs are present as well. Treatment with DNase I results in multiples of 10 bases when analysed under denaturating conditions. These results show that the general organization of the DNA within the nucleosomes is about the same in higher plants as in other higher eukaryotes.


A compact from of methylated DNA is solutions containing poly (ethylene glycol). Some peculiarities of compactization of double-stranded DNA molecules containing methylated nitrogen bases have been studied in water-salt solutions of PEG. It is shown that the methylation of N7-atoms of guanyl residues in original DNA molecules does not prevent the formation of DNA compact particles, but results in a decrease of the amplitude of the negative band in the CD spectrum of compact particles. The influence of N7-guanine methylation on the shape of the CD spectrum being the greater, the lower is the concentration of PEG. The dependence of the negative band amplitude in the CD spectrum on the content of methylated guanyl residues is practically the same for low-molecular weight DNA's from different sources. The observed decrease in the negative band amplitude is interpreted as a result of alterration of guanyl residue orientation relative to the helix axis which leads to diminished optical activity of the "microcrystalline" domains of compact particles. The evidence obtained suggests that changes in the secondary structure of DNA lead to considerable difference between CD spectra of compact particles of methlated DNA and psi-form of DNA. (The changes in the CD spectrum of the DNA compact particles occur also as a result of methylation of C5-atoms of cytosine residues). It is suggested that the negative band in the CD spectrum can be used a criterion for detection of negligible alterations in the DNA secondary structure.


Chronic disease and short stature.

Chronic disease and short stature. Careful graphing of the anthropometric measurements of children with chronic disease and short stature should be done to determine height and weight growth velocities. In addition, a detailed history can provide information helpful in determining the expected growth curve. If the chronic disease can be effectively treated (eg, malnutrition, emotional deprivation, celiac disease, asthma, rheumatoid arthritis), a period of rapid "catch-up" growth can be anticipated. The prognosis with regard to adult stature depends on the timing, duration, and severity of the growth-inhibiting influence.


Abdominal examination: role of percussion and auscultation. Clinicians should not minimize or overlook the importance of percussion of the liver and the spleen and of auscultation over the liver as routine parts of abdominal examination. Splenic percussion can be used to detect splenomegaly even before the spleen becomes palpable. The span of liver dullness on percussion can be compared with established normal standards to detect hepatomegaly or alterations caused by cirrhosis. A systolic bruit, a friction rub, or a venous hum detected by auscultation over the liver is an important sign of liver disease.


Fat embolism syndrome: a puzzling phenomenon. Fat emboli are a life-threatening source of respiratory insufficiency. Whether they are of mechanical or chemical origin remains a subject of controversy. Fat embolism syndrome is most often seen after fracture of long bones, and immobilization of the fracture site may decrease risk of its development. Adequate oxygenation is the most important aspect of therapy; most patients given vigorous supportive treatment recover with no residual lung injury.


Growth abnormalities in genetic syndromes. The presence of a growth abnormality may be documented by determination of growth velocity, calculation of the upper segment/lower segment ratio or the AF/AT ratio, and measurement of head circumference. Important considerations in differential diagnosis of specific malformation syndromes are birth weight, limb and truck alterations, head size, physical features, and presence or absence of mental retardation. Additional clinical measurements, such as measurement of chest circumference and of finger and hand length, may be useful in selected cases. These data, combined with historical information, can indicate a specific diagnosis and facilitate the choice of confirmatory laboratory studies.


Endocrine causes of short stature.

Endocrine causes of short stature. The primary clinical characteristic of shortness of stature due to endocrine deficiency is a slow rate of growth (less than 1.5 in., or 4 cm, each year). Dental and skeletal ages are delayed. Specific tests of thyroid and pituitary function must be done to document the deficiency. Replacement therapy with levothyroxine or human growth hormone, or both, should be given as indicated. Short children who do not have hormone deficiency grow about 1.5 in. (4 cm) each year but have normal skeletal and dental ages. Children with Turner syndrome, primordial or genetic short stature, or intrauterine growth retardation do not respond to levothyroxine or human growth hormone replacement therapy. Constitutional delay in sexual development is a common cause of short stature in adolescent males and must be differentiated from hypopituitarism.


Endomyocardial firbrosis and Löffler's endocarditis parietalis fibroplastica. The morphological features of endomyocardial fibrosis and Löffler's endocarditis are described. Sixteen cases of the chronic stage of Löffler's endocarditis were compared with pathological material of thirty-two patients with endomyocardial fibrosis. No morphological differences were noted. It is suggested that endomyocardial fibrosis and LOffler's endocarditis are part of the same disease spectrum, the origin of which can be traced back to the presence of eosinophils in the myocardium.


The general practitioner's information requirements in prescribing. A general practitioner's requirements can be described in terms of three levels. These three levels are described and discussed with reference to examples from the author's own experience.


Information and prescribing from the hospital doctors' viewpoint. The requirements of a hospital doctor are viewed under the headings of 'active' and 'passive' information. The emphasis is placed on the practical value of information aimed at the prescribers, and the conclusion reached is that the information should be disease- rather than drug-orientated.


Departments of clinical pharmacology and therapeutics as sources of data. The functions of a clinical pharmacologist are described and some questions worth asking when prescribing drugs are listed and briefly discussed.


Hospital pharmacy information centres and their role as suppliers of information. The development of the drug information services within the hospital area is described from its origin in America. The services currently available in the NHS are outlined and a description of the type of enquiries handled is given.


Representatives and advertisements as sources of information. The role of the representative and advertisements as information sources is discussed. Emphasis is placed on these as providing only part of the whole data package available to a doctor to enable him to make his prescribing decision.


Information centres in the pharmaceutical industry--the prime source of drug information. The case is argued that the prime source of information is the manufacturing company. The medical information department of an average-sized company is used as a model to support this argument.


Tumoral calcinosis: a manifestation of extreme metastatic calcification occurring with 1, alpha-hydroxycholecalciferol therapy. Two cases are reviewed, both of which developed tumoral calcinosis whilst receiving 1, alpha-hydroxy-cholecalciferol therapy. Tumoral calcinosis is an extreme form of peri-articular calcification, and its occurrence in patients with chronic renal failure is unusual. These peri-articular masses developed around the shoulders in both patients, and the action of 1, alpha-hydroxycholecalciferol as a possible factor promoting this form of metastatic calcification is discussed.


[Characteristics of development of diabetic neuropathy depending on sex of diabetic patients]. The authors present the results of clinico-neurological study on 3976 patients suffering from diabetes with the use of electrophysiological, biochemical and other methods. As revealed, the sex of diabetic patients, particularly at definite age periods produced a significant influence on the time of occurrence and the rate of development of various types of the central and peripheral neuropathy. Thus, at the age of under 30 years almost all the types of diabetic neuropathy originated earlier and developed more rapidly in women, and after the age of 50 years some of these types of neuropathies were more frequent and more pronounced in men. No significant differences in the incidence of many types of diabetic neuropathy were revealed at the age of from 30 to 50 years both in men and in women. The mentioned regularity was most distinctly traced in analysis of distal pelyneuropathy. A hypothesis is put forward on the causes inducing peculiarities of the diabetic neuropathy development depending on the sex factor.


[Sensitivity of the isolated adipose tissue to insulin in obesity with presence or absence of diabetes mellitus]. The authors studied the sensitivity of the isolated adipose tissue to various insulin concentrations in healthy women and also in women suffering from adiposity with the normal and diabetic test for glucose tolerance. Adipose tissue sensitivity to insulin was studied by the influence of insulin to the intensity of incorporation of carbohydrate of labeled glucose into the common lipids of the adipose tissue in its incubation with various insulin concentrations. A marked reduction of the adipose tissue sensitivity to physiological concentrations of insulin was shown in patients with adiposity. The extent of insulin sensitivity fall was the same in such patients with normal glucose tolerance and in those suffering from latent diabetes. A conclusion was drawn that the mentioned reduction of adipose tissue sensitivity to insulin could serve as a significant factor leading to the development of diabetic disturbances in adiposity. Another factor playing an important role in the development of diabetic disturbances in adiposity was compensatory possibilities of beta-cells of the pancreas.


[Lymphography of the thyroid gland. 1].

[Lymphography of the thyroid gland. 1]. The authors carried out a lymphographic examination in 11 patients with various diseases of the thyroid gland. Lymphography proved to be an effective and harmless diagnostic method in pathological changes of the thyroid gland. Different structure of the thyroid gland tissue was revealed on the lymphograms depending on the character of the pathological process. In establishment of the diagnosis one should take into consideration the structure of the thyroid gland tissue, the structure of the cervical lymph nodes, and possibilities of their filling with the contrast agent, the amount, the rate and difficulties encountered in the administration of the contrast substance.


[Electroroentgenoscanning of the thyroid gland]. A significant drawback of the radioisotopic scanning of the thyroid gland is the absence of a distinct knowledge of topographo-anatomical associations of this gland with other organs and tissues. To eliminate the mentioned drawback the method of electroscanning (combined electroroentgenography and radioisotopic scanning in two interperpendicular projections) was introduced into practice of the regional hospital. Electroscannograms were prepared on paper by means of the apparatus made in the USSR: roentgenograph ERGA-MP, gammatopograph GT-2, and roentgenodiagnostic unit ARD-2. The principle of the method consists in recording the scannogram of the gland on the preliminarily prepared electroroentgenogram of the cervical area and of the upper part of the chest in the horizontal position of the patient. Lead labels attached to definite areas of the patient's skin were used for matching the scannogram with the electroroentogenogram. This method differs from routine seannography of the gland by the fact that it provides an additional topography-anatomical information; it can be used in any radioisotopic diagnostic laboratory equipped with a scanner.


[Bioelectrical activity of the brain in men with hypogonadism]. Bioelectrical activity of the brain was studied in 51 patients with primary and in 36 with secondary hypogonadism. In the patients examined there was a change of both the amplitude and frequency characteristics of the EEG curves; organization of the basic rhythm was disturbed, and paroxysmal activity discharges appeared. The EEG data in primary hypogonadism pointed to reduction in the reactive properties of the cortex and brain stem; in secondary hypogonadism--diffuse affection of the diencephalic region was testified to.


[Study of the androgenic activity of the ovaries in various forms of virilism of ovarian etiology]. The authors present the results of determination of the testosterone level in the blood by the method of competitive fixation by proteins under conditions of a functional test with the depression of the adrenal cortex function with dexamethazone and stimulation of the ovarian function with choriogonin against this background in patients with the virile syndrome of ovarian genesis. Three groups of patients with the ovarian hyperandrogenia were distinguished. Changes in the blood testosterons level under the test conditions confirmed objectively the ununiformity of of this syndrome and permitted one to characterize the hormonal activity of the androgen-producing structures of the ovaries and their sensitivity to choriogonin stimulation in patients of different groups. The functional test with the determination of the blood testosterone level can be applied under clinical conditions for detection of the source and the degree of hyperandrogenia.


[Characteristics of the water-electrolyte regulation in experimental hyperthyroidization and hyperthyroidism]. In experiments on rats the effect of hyperthyroidization (induced by thyroidin, 1-thyroxin) and hyperthyrosis (induced by TSH, cold exposure) on volume natriuresis was studied. As revealed, after expansion of extracellular space natriuresis increased under hyperthyroidization and hyperthyrosis, and was much higher than in control rats. Natriuresis elevation in response to increased volume of extracellular fluid in rats under hyperthyroidization resulted from the rise of natriuretic factor in the blood.


[Degradation of prolactin 125-I in the mammary gland of lactating rats]. Prolactin-125I metabolism in the mammary gland of lactating rats was studied; the hormone was injected intraperitoneally. Radioactive products accumulated by the mammary gland tissue were extracted with isotonic medium. Tissue extracts, blood serum and milk were analyzed by gel filtration on Sephadex G-200. The Blood displayed a gradual reduction of prolactin-125I content as a result of its splitting in the organs and binding with blood proteins; as to the mammary gland--there occurred accumulation of the products of prolactin-125I degradation. Some hormone was inactivated losing immunological properties without any significant changes in the molecular weight. Besides, the mammary gland displayed an intensive accumulation of the products of prolactin-125I splitting in the other organs and in the gland proper. Radioactivity accumulated in the milk was mainly referred to the products of prolactin-125I degradation. There was also shown the presence of immunologically active prolactin-125I in the milk.


[Adrenal cortex function and development of vascular changes in rabbits with alloxan diabetes]. The role of adrenal cortex hormones in the development of vascular changes was studied in 16 rabbits with alloxan diabetes. Formation of morphological changes in the aorta proved to be partially determined by functional condition of the adrenal cortex at the early periods of alloxan diabetes.


[Seasonal differences in the sensitivity of the catecholamine receptors of the brain in connection with the endocrine function of the pituitary-testicular complex]. The fluorimetric method was applied to the study of testosterone level in the peripheral blood plasma after the administration of substances stimulating catecholamine receptors of sexually mature Wistar male rats at different seasons of the year. Dophamine administration (a dose of 10 microgram) caused an increase in the blood testosterone level (twice) both in summer and in winter. At the same time noradrenaline stimulating chiefly the alpha-adrenoceptors and isopropylnoradrenaline (novodrin) acting chiefly on beta-adrenoceptors produced a stimulating action in the same doses in summer only. In winter the activation of the hypothalamo hypophysio-testicular complex was noted after the administration of these substances into the lateral ventricle in a dose of 100 microgram only. A conclusion was drawn that, in difference from dophamine receptors, sensitivity of alpha- and beta-adrenoceptors connected with the endocrine function of the hypothalamo-hypophysio-testicular complex depended on the seasonal factors. It is supposed that the brain adrenoceptors were capable of participating in the regulation of seasonal dynamics of testosterone content in the blood.


[Thyrotropic activity of the pituitary gland in rats at various age periods]. The thyrotropic activity of the hypophysis (TTH synthesis and secretion) was studied in rats at various age periods. The work was conducted on mongrel male rats of four age groups: 1 1/2-2, 8-10, 18-24, and 28-32-months old. Being relatively low in the sexually immature animals, the thyrotropic activity of the hypophysis considerably intensified in adult rats and diminished with the ageing of the organism. A reduction of the TTH synthesis and secretion in old animals, testified to by the hormone content in the hypophysis and the blood, was apparently connected with the intensification of the T4-deiodating capacity of the hypophysis tissue.


[Study of the role of sialic acids in the formation of bound form of insulin]. In studying the formation of insulin complexes with transferrin the role played by sialic acids in this process was ascertained. The role of terminal sialic acids, included into the glycoprotein composition, in the formation of complexes of these glycoproteins with a number of components circulating in the blood was noted earlier. To study the role played by sialic acids of transferrin molecule in the formation of complexes with insulin the author used transferrin untreated and treated with neuraminidase, an enzyme splitting the sialic acid molecules from grycoprotein specifically. The influence of these preparations on the biological activity of insulin was studied. Transferrin devoid of sialic acid lost its capacity to form complexes with insulin. Control experiments demonstrated that by itself neuraminidase treatment of preparations of transferrin and insulin failed to influence their biological activity. The results of experiments with the use of neuraminidase demonstrated that sialic acid in donor transferrin molecule could be of great significance in the formation of an insulin-transferrin complex.


Proliferation of primary cultures from rat aortic media. Effects of hyperlipemic serum. Tissue cultures have been made from explants of thoracic aortas to study the growth pattern of rat aortic mediacytes. Three parameters were measured weekly: the surface of the culture, the relative increase of this surface and the number of 3H-thymidine labelled cells per unit surface. The primary cultures showed two distinctive phases: a first phase with continuous growth followed by a plateau phase. We studied the growth effect of homologous hypercholesterolemic serum added to the cultures. The cell proliferation was affected by the cholesterol level in the medium and the stage of the culture at which serum incubation was initiated. An enhancing effect occurred in the rat resistant to such treatment in vivo.


Arterial permeability to labeled protein. Labeled albumin, which was administered intravenously, was detected, with the use of a scintillation counter, in the aortic wall of rabbits. Relative to weight, the permeability index was highest in the aortic arch and abdominal aorta and lowest in the medial thoracic aorta. Angiotensin II and various mediators were found to increase the permeability of the aortic wall.


Endothelial cell injury in early mild hypercholesterolemia. Hypercholesterolemia was induced in 6-week-old male swine by feeding them a chow diet supplemented with lard and cholesterol. Aortic samples from areas of spontaneously-differing permeability to proteins, as demarcated by their uptake of Evans blue dye, were prepared and examined using light microscopy and scanning and transmission electron microscopy. At 2, 4, and 6 weeks after diet initiation, cholesterol/lard-fed animals demonstrated leukocyte adhesion to aortic endothelium in both greater (blue) and lesser (white) permeability areas, being greaer in the former. Endothelial cells underlying leukocytes were generally normal in ultrastructural appearance, but showed cytoplasmic uptake of ruthenium red. Endothelial cells in cholesterol/lard-fed animals contained more lysosomes and cytoplasmic filaments than seen in control animals. Blood-derived cells were more frequently seen in the intima of cholesterol/lard-fed animals, and were often observed associated with intercellular junctions in the endothelium.


Spontaneous endothelial cell injury in the intimal cushions of atherosclerotic pigeons. Since endothelial damage precedes sterol accumulation, platelet factor 4-like activity elevations and alterations in thrombocyte adhesiveness, it clearly is one of the earliest events in the pathogenesis of spontaneous pigeon atherosclerosis. Although the relationships among endothelial damage and the other events have not been elucidated, it is conceivable that products released from thrombocytes subsequent to adhesion on damaged endothelium may trigger other localized changes in the intimal cushion area and lead to the progression of atherosclerosis.


Is the sclerotic vessel wall really more rigid than the normal one? Quasistatic passive mechanical properties of fibrosclerotic and normal human anterior cerebral arteries were studied in vitro. Mechanical properties were characterized by incremental elastic modulus, strain energy density and incremental distensibility for a 20--250 mm Hg intraluminal pressure range. Fibrotic arteries were found to have a 34--45% lower elastic modulus at the same pressure levels than normal ones (p less than 0.01--0.02). Distensibility however proved to be only 28--35% higher in the fibrotic group, this difference was significant just at a few pressure values above 120 mm Hg. This was due to the opposite changes in elastic properties and radius to wall thickness ratio. It is supposed that higher elasticity of the fibrotic arterial wall is the consequence of a local compensatory process tending to prevent pathological alterations in distensibility of the arteries.


Genetic factors in the development of atheroma and on serum total cholesterol levels in inbred mice and their hybrids. There is a consistent genetic relationship between the development of atheromata in the aortic sinus wall and serum total cholesterol levels using inbred strains of male mice. This relationship is dependent on a multifactorial (polygenic) type of inheritance that is more complicated than the simple additive-dominance model. There is no special maternal or paternal influence on serum total cholesterol levels or on the development of atheromata.


Smooth muscle cell changes of media underlying experimental arterial thrombosis. The is much evidence that platelet thrombi release many factors which can alter endothelial permeability and may alter other cell membrane permeability. A large thrombus could also interfere with the diffusion of oxygen to the inner media. In either case injury of the medial cells may affect their ability to metabolize lipid.


Platelets, thrombosis and atherosclerosis. The interaction of platelets with the vessel wall can contribute to the early stages in the development of atherosclerosis through effects on smooth muscle cell proliferation, endothelial permeability, and possibly by causing vessel wall injury. Platelets are involved in the development of thrombi in response to vessel injury, and the repeated formation of platelet emboli and platelet-fibrin emboli from the mural thrombi may be one of the factors that cause clinical complications of atherosclerosis. Drugs which inhibit platelet function, particularly those that prolong shortened platelet survival (sulfinpyrazone and dipyridamole) may prove to be important in inhibiting the response of blood to vessel injury and thereby modifying the extent of atherosclerosis and its complications.


Photometric platelet aggregation test III: a new tool for the detection of enhancet platelet aggregation. In clinical investigation on ehnanced platelet aggregation the changes of the various tests with time after blood sampling must be considered. The photometric PAT III for the evaluation of spontaneous aggregation showed enhanced aggregation in a high percentage of patients with vascular disease, and prospective data obtained so far make it likely that enhanced aggregation is a risk factor for thrombosis. More prospective studies are necessary to prove whether continuously enhanced spontaneous platelet aggregation is indicating progressive atherosclerosis.


Platelet-mediated pulmonary hypertension: reduction by platelet inhibition. Altering the platelet behavior with sulfinpyrazone or heparin--probably by inhibiting the platelet release reaction--reduces the emboli-induced pulmonary hypertension to the same extent as platelet depletion. Evaluation of platelet function in human pulmonary microembolism and consideration of substances which minimize or prevent platelet effects seems to be warranted on the basis of these experiments.


Relationship between disturbed rheological properties and cerebral hemodynamics in recent cerebral infarction. In 75 patients with neurological symptoms due to RCI serum fibrinogen, whole blood viscosity and platelet aggregability have been determined before treatment was started. In addition, in 24 of the patients also HBF has been measured. In patients with RCI viscosity was significantly increased. Serum fibrinogen was higher at increased viscosity levels and when enhanced platelet aggregation was evident. At low shear rates increased blood viscosity correlated significantly with serum fibrinogen as well as with reduction of HBF.


Derivation of intimal smooth muscle cells in normal arteries and atherosclerotic plaques. An overview. We have no evidence of the precise derivation of myointimal cells, either in 'normal' intima or in atherosclerotic lesions. Neither has any derivation been eliminated. Efforts to establish the origin of the cells might be as helpful to our understanding of the lesions as have been the studies of proliferation of SMC, regardless of which one of the various theories of the pathogenesis of atherosclerosis we happen to support.


Proliferation of arterial smooth muscle: glucocorticoid effect. Tritiated thymidine radioautography was employed to study the effect of glucocorticoids on smooth muscle proliferation in rabbit arteries. In the aorta and pulmonary artery of rabbits with cholesterol atherolsclerosis, labelled cell counts showed that these steroids decrease the deoxyribonucleic acid synthesis in the intimal plaques. The inhibitory effect on thymidine uptake was found to be dose dependent and closely related to the antiinflammatory potency of the steroid tested. In another set of experiments the smooth muscle proliferation occurring in the rabbit carotid artery after disendothelization was studied. In these normolipemic animals the inhibition of DNA synthesis was particularly evident in the medial smooth muscle cell; concomitantly, in steroid-treated animals the myointimal thickening in the denuded area was less prominent. It is concluded that very likely the glucocorticoid effect on the artery is due to a direct interaction of the steroid with smooth muscle cells.


Smooth muscle cell response to endothelial injury. Electron microscopy and autoradiography with 3H-thymidine have been employed to study the cellular dynamic of intimal thickening occurring in the rabbit carotid artery after selective endothelial injury. The results obtained suggest that migration of SMC of the tunica media rather than proliferation is the key event in the development of the intimal thickening.


Calcium channels in Paramecium aurelia.

Calcium channels in Paramecium aurelia. Reversal of swimming direction in paramecium is dependent on the calcium influx through the excitable-membrane calcium channels. Several mutants of Paramecium aurelia have been selected on the basis of their resistance to the paralyzing effect of barium. The mutants have reduced reversal behavior and are in the same three pawn genes as discovered by Kung (16, 17). Also, in barium solutions, the pawns live longer than the wild-type; however, pwB mutants are more resistant to barium toxicity than pwA mutants. These results suggest that the selection picked up mutants in the calcium channel. Electrophysiological studies demonstrate this point directly, showing defective calcium activation in all pawns, but also defective anomalous rectification in pwB mutants. A model is presented which accounts for the differences between pwA and pwB mutants. It ascribes the depolarization-sensitive "gate" function to the pwA gene product and the "pore" function to the pwB gene product. Additionally, the stability of the channel structure is demonstrated, channel half-life being from five to eight days.


Acetylcholine receptors and myasthenia gravis: the effect of antibodies to eel acetylcholine receptors on eel electric organ cells. Antisera to acetylcholine receptors purified from Electrophorus electricus were tested for their ability to bind to receptors on electric organ cells, block the depolarizing response of the cells to carbamylcholine, and inhibit binding of 125-I-alpha-bungarotoxin to the cells. It was found that although antibodies could bind to most of the receptors, resulting in substantial inhibition of the depolarizing response, binding of 125-I-alpha-bungarotoxin to the cells was only slightly inhibited. This was consistent with the observation that these antibodies did not compete for the toxin binding site on detergent-solubilized receptor. These results suggest that the antibodies inhibited receptor activity primarily by interfering with the ionophore of the receptor or its regulation by the acetylcholine binding site. However, the possibilities could not be completely eliminated that blockage of a small fraction of the binding sites caused a large inhibition of the depolarizing response or that bound antibody allosterically reduced binding affinity for carbamylcholine without completely inhibiting toxin binding.


Studies on cell recognition in the developing brain. Several lines of evidence demonstrate cell-cell receptors on the surface of developing brain cells. Plasma membrane vesicles with regional and temporal binding specificities can be prepared. Active factors that block cell aggregation can be extracted from these membranes and partially purified. Quantitative studies of cell-cell adhesion demonstrate a gradient of adhesive specificity along the dorsoventral axis of the developing retina.


Lectin activity in embryonic chick muscle: developmental regulation and preliminary purification. Soluble extracts of embryonic chick pectoral muscle contain lectin activity. This activity is assayed by agglutination of trypsin-treated, glutaraldehyde-fixed rabbit erythrocytes, and is blocked by specific saccharides such as thiodigalactoside and lactose. Lectin activity of the muscle extracts increased at least 1 order of magnitude between 8 and 16 days of chick embryo development, as the pectoral muscle differentiated. Preliminary purification was achieved by affinity chromatography on Sepharose 4B deprivatized with either asialo-bovine glycoprotein, or p-aminophenyl beta-D-thiogalactopyranoside as the ligand.


Biochemical studies of the common and restricted antigens, two neural cell surface antigens. Two cell surface antigens on rat neural tumor cells are defined by antisera from mice immunized with a rat glioma cell line, 33B. The Common antigen is on rat brain and embryo, and is strongly expressed on the surface of all, or most, rat glioma and neuroblastoma cell lines and tumors. The other Restricted antigen is not present at detectable levels on normal rat tissues, but is on 33B, and on 11 other rat neural tumors or cell lines developed from such tumors, though many other tumors are negative. These 2 antigens are on cell membrane preparations from cells and tumors, and have been further characterized using a quantitative antigen assay. Both antigens are heat labile, and can be destroyed by digestion with proteolytic enzymes. The Common antigen is 10 times more sensitive than the restricted antigen to pronase digestion. Furthermore, spacially separate sites for the 2 antigens are indicated by blocking experiments with pepsin digested antisera. Attempts to purify these antigens further have been frustrated by loss of antigenic activity upon detergent-induced release from the membrane. The tissue and tumor distributions of recently described mouse and rat surface antigens are reviewed. Many of these antigens are present on both brain and kidney, but not on other tissues, though several are shared with embryonic cells or sperm. Several new antigens have been described which may be neuronal specific.


Interaction of the lipid-associating domain of glycophorin with phospholipid bilayers. The MN-blood group bearing glycoprotein of the human red cell membrane, glycophorin, has been shown to traverse the membrane in vivo such that the NH2-terminal portion is exposed to the external, and the COOH-terminal portion exposed to the cytoplasmic, mileiu. The intervening 23 residue lipid-associating domain (LAD) of glycophorin has been shown to have a unique overall hydrophobicity. The LAD of glycophorin can be obtained intact within an aqueous insoluble tryptic peptic, T(is). Under appropriate conditions (the reaction not being spontaneous), T(is) can be associated with phospholipid bilayers. Freeze fracture studies of T(is): phospholipid vesicles suggest that T(is) forms multimeric torus-shaped intramembranous structures 80 A in diameter with n greater than 4. The plot of T(is) concentration versus multimer density suggests there is a critical multimer concentration (CMC) for T(is) in phospholipid bilayers (L/P = 200/1). Various physico-chemical techniques such as pyrene fluorescence spectroscopy, differential scanning calorimetry, and ionic permeability were used to investigate the T(is)-lipid association. Results indicate that this system is an excellent one in which to study the boundary lipid phenomenon. In addition, T(is) association with lipid bilayers is being correlated with the natural state of glycophorin in the red cell membrane.


Adhesion among neural cells of the chick embryo. Cell-cell binding of both retinal and brain cells of the chick embryo varied as a function of developmental age, brain cells acquiring their binding properties at an earlier time than retinal cells. Brain and retinal cells of the appropriate age bound as well to each other as to themselves. Antibodies prepared against a molecule released by retinal cells in culture were able to inhibit cell-cell binding between homologous and heterologous pairs of retinal and brain cells. These results suggest that the molecular mechanism of cell-cell binding is the same in these 2 tissues. Analysis of cell surface proteins precipitated by these antibodies suggest that one of the molecules involved in adhesion has a molecular weight of 150,000, and may be derived from a larger precursor. The possible mechanisms of cell-cell binding are discussed in terms of the properties of this molecule.


Factors influencing degradation of extrajunctional acetylcholine receptors in skeletal muscle. During development and after both denervation and reinnervation in adult mammalian skeletal muscle, the level of acetylcholine (ACh) receptors in the extrajunctional membrane undergoes wide variation. We have determined the rate of extrajunctional receptor degradation in denervated muscles in organ culture under a variety of conditions by measuring the rate at which alpha-bungarotoxin bound to the receptors is degraded. Direct electrical stimulation of muscles for several days dramatically reduced the levels of extrajunctional ACh sensitivity, and also reduced the rate of receptor degradation. Since the effect of activity on the rate of receptor degradation is in the opposite direction of the observed change in receptor levels, we conclude that activity must also decrease the rate of receptor synthesis. Receptor degradation was also examined in muscles at various times after denervation. The half-time of degradation increased from approximately 7 hr at 2-5 days after denervation to approximately 14 hr at 10-14 days. Hypophysectomy, which decreases the average rate of protein degradation in muscle, also decreased the rate of extrajunctional receptor degradation, but thyroxine, which restores the normal rate of overall protein breakdown in hypophysectomized animals, did not affect receptor breakdown. Since hypophysectomy did not increase the level of extrajunctional ACh receptors, it must also affect ACh receptor synthesis.


Selective enzymatic hydrolysis of nerve terminal phospholipids by beta-bungarotoxin: biochemical and morphological studies. beta-Bungarotoxin, a presynaptic protein neurotoxin isolated from the venom of the snake Bungarus multicinctus, modifies release of neurotransmitter at the neuromuscular junction. The toxin has a potent phospholipase activity toward both natural membranes and phospholipid liposomes. Studies of ionic requirements and selective chemical modification demonstrate that beta-bungarotoxin can only modify synaptic transmission under conditions in which the phospholipase is active. Morphological studies on frog cutaneous pectoris neuromuscular junctions incubated with beta-toxin and horseradish peroxidase-conjugated beta-toxin support the hypothesis that beta-toxin specifically interacts with presynaptic plasma membranes and selectively hydrolyzes nerve terminal phospholipids.


Factors influencing monolayer cell culture morphology and survival of cerebellar granule cells from wild-type and mutant mice. A distinction must be made between genetic factors intrinsic and extrinsic to a specific degenerating cell type if neurological mutants that show such effects are to be used to assess cause-and-effect correlations of neural development. When the growth of granule cells from cerebella of staggerer mutant mice is investigated in monolayer cell cultures using modified Hams F12 medium plus fetal calf serum, cells from the mutant are found to clump less and survive longer than their wild-type counterparts. Thus, the degeneration of granule cells observed in these mutants in vivo cannot be a function of irreversibly programmed cell death before postnatal day 7, the age at which cells are dissociated. The possibility that the increased survival is simply a function of initial cell-cell interactions is examined by comparing normal cells grown on glass, plastic, or polylysine-coated glass to each other, and then comparing the behavior of staggerer vs control cells under the same conditions. Although the polylysine coating both reduces the amount of initial clumping and increases the survival of normal cells, it does not completely eliminate the difference between mutant and control. Mutant and control cultures exhibit the same behavior only when culture conditions are changed to include supplementation with horse serum instead of fetal calf serum in addition to the substrate coating.


Permeability and phase-boundary potentials determined from conductance in a transmitter-activated potassium channel in Aplysia californica in the absence of a constant field. A potassium-selective, chemically excitable channel, whose characteristics cannot be accurately described by "constant field" theory, is studied using a new approach based on diffusion theory but having no need for the classical assumptions of constant field, homogeneous membrane, and equal phase-boundary potentials at both interfaces. Permeability is defined, free of these constraints, and the Goldman coefficient is demonstrated to be a special case useful only when the constraints apply. Permeability can be evaluated directly from chord conductance, and it is found not to be a parameter in this channel, but rather a function of both the voltage and the concentration of the permeant ion. However, it becomes concentration-independent when the membrane voltage is equal to the sum of the phase-boundary potentials. That sum can therefore be determined from these data, and it is -65 mV in this channel. The permeability at that potential is a channel parameter, and equal to 8.77 (10)-6 cm/sec for this channel. A constant field is shown not to exist in this channel, and the Goldman coefficient not to be a parameter but a function of potential and concentration. Although errors introduced into this coefficient by nonconstant field and unequal surface potentials partially cancel each other, the coefficient is nevertheless not a correct measure of permeability.


Biochemical investigations of retinotectal specificity. An in vitro assay for retinotectal specificity has been described. The results show that, in the chick embryo, cells dissociated from the dorsal retina preferentially adhered to ventral tectal surfaces while cells from the ventral retina preferentially adhered to dorsal tectal surfaces. These adhesive preferences thus mimic the retinotectal specificity observed in vivo. The assay has been extended for use with plasma membrane preparations from retinal cells. Experiments in which retinal cells or tectal surfaces were treated with purified proteases and glycosidases have partially characterized the moieties responsible for the observed specificities. These results are consistent with a double gradient in the dorsal-ventral axis of complementary proteins and carbohydrates. The carbohydrate moiety would be expected to terminate in an acetylated hexosamine and to be more concentrated dorsally in both retina and tectum. A protein that is complementary to the hexosamine terminus would be localized in the ventral part of retina and tectum.