[Cerebral infarction and migrainous attack. Angiographic and CT scan studies (author's transl)].

A lateral homonymous hemianopia appareared in a 40 years old housewife during a migrainous attack and persisted as sequella. Angiographic study was normal and CT scan showed an area of low density at the right occipital level enhancing with heterogenous aspect after the iodinate injection. The occurrence of a cerebral infarction during a migrainous attack is probably due to numerous factors.


[The treatment of headaches: an open randomized comparative therapeutic study (author's transl)].

An open, randomized clinical trial was carried out to compare the therapeutic efficacy of two products in the treatment of headaches. A total of 65 patients were prescribed tiapride and a similar number were given dimetotiazine (neuroleptic indicated in migraine and headache). Tiapride was prescribed as 3 tablets a day for the first 24 hours, followed by 1/2 a tablet three times daily. Excellent or good results (improvement of 60% or more), were obtained in 49 patients (75%). Results after dimetotiazine, at the recommended dosage of 2 capsules during the first 24 hours followed by 1 capsule at night, gave 30 excellent or good results (46%). There is a highly significant difference (p less than 0,01) in favour of tiapride. Both products were well-tolerated.


[A case of temporal arteritis accompanied with appearance of "cold areas" on the liver scan (author's transl)].

The authors report a case of temporal arteritis accompanied with appearance of "cold areas" on the liver scan, regressing after steroid therapy. This observation confirms the existence of hepatic manifestation in giant cell arteritis and evokes a discussion of their mechanism. A hypothesis of hepatic ischemia is proposed.


[Unusual ischemic cord compression by discal hernia (author's transl)].

The discal hernia are unfrequent in dorsal localization and neurological appearances are deceptive. We report a case with amyotrophic and fasciculations developing a progressive spinal cord amyotrophy aspect. The complementary investigations (gaz myelography and spinal angiography) show the discal hernia in T11-T12 which was operated successfully. The vascular factor role is discussed about semiologic and pathogenic view.


[Recent results concerning muscular disorders arising from thyroid gland dysfunction (author's transl)].

The right number of muscular disorders which may be observed clinically in thyroid dysfunction contrast with the paucity of knowledge concerning the mechanisms of action of the thyroid hormones. Those which have been described allowed the following conclusions to be made: 1) The thyroid hormones simultaneously increase the oxydative phosphorylation in mitochondria and the activation of glycogen phosphorylase. 2) They modify the properties of cell membrane without noticiably changing the cytoplasm (light and electron microscopically). These modifications are concommitant with a reduction in resting membrane potential associated with anomalies of Na+ conductance and Ca+ uptake. 3) The appearance and the number of motor units in each muscle is dependant on the hormonal impregnation. However, these diverses actions do not reveal wether the thyroid hormone receptors are in the muscle or if they act via the intermediary of a neuronal trophic factor.


[Asymetrical gonadal dysgenesis. Report of a case (author's transl)].

The authors report a case of asymetrical gonadal dysgenesis related to 45XO-46XY mosaicism in a 16 year old girl. Delayed, growth and puberty, Turner's dysmorphism without sexual ambiguity and skeletal abnormalities are the main clinical features suggesting the diagnosis. Exploratory laparotomy reveals infantil uterus, bilateral falopian tubes and streak gonads. A right dysgenetic testis is identified on electron microscopic examination. Theories on pathogenesis of this unusual genetic defect are discussed.


[Hypercalcemia and osteoclast activating factor (OAF) associated with acute lymphoblastic leukemia (author's transl)].

The occurence of hypercalcemia appears to be unusual in leukemia. The mechanisms are numerous: secretion of PTH of PTH like substance, prostaglandin E2 or vitamin D like sterols. The reported case is one of lymphoblastic acute leukemia and hypercalcemia associated with osteoclast activating factor secreted by leukemic cells. In this patient the serum levels calcium closely paralleled the course of acute leukemia.


[Nephretic colic in patients with arrhythmia (author's transl)].

The authors relate one case of obstruction by emboly in the renal artery. The diagnosis were too late for conservative surgery. In this case, they insist on the particulary signs of that nephretic colic and they show the diagnosis measures which are able to permit a conservative surgery in urgency.


[Present position of radiotherapy in the treatment of lymphomas other than Hodgkin's (author's transl)].

The authors would remind us that the classification of the hemato-sarcomas is at present being reorganized and that, lymphosarcomas are appearing more and more in the form of disseminated diseases sensitive to chemotherapy as well as radiotherapy. It is highly recommended that first a pre-therapeutic check be carried out in order to classify the disease into one of the five stages before deciding on the therapy. The authors report on the association of radiotherapy and chemotherapy and the role of each as used in their treatment of the disease, at present.


[Report of a new case of purpura due to an IgA (K) - IgG cryoglobulinemia (author's transl)].

The authors report a new case of purpura due to an IgA (K) - IgG cryoglobulinemia, which is a rare immunological event. They recall the main clinical, etiological and therapeutic data of "essential mixed cryoglobulinemia" and compare this observation to other similar cases of the literature.


[Hereditary chronic pancreatitis: an autosomal dominant disease (author's transl)].

We have studied a family in which three people, two child and an adult had hereditary pancreatitis. Hereditary pancreatitis is not a common disease. Abdominal pain is usually the first clinical sign in children. The knowledge of the existence of such a disease and familiarity with the family history of the child allow the pediatrician to make the diagnosis as soon as the first crisis appears. Surgery is thus avoided. Our studies show definitively that this disease is hereditary and is autosomal dominant with a strong decrease of the penetrance.


[Fulminating pneumococcal septicemia (author's transl)].

Two cases of fulminating pneumococcal septicemia (FSP) are reported, and 47 confirmed cases were discovered after a review of the published literature. The syndrome is that of a malignant infection with fever, collapse, and disseminated intravascular coagulation, with a rapid mortal outcome in most cases. Etiologically, FSP is usually the consequence of functional or anatomical asplenia, and the relative frequency of this affection after splenectomy following trauma confirms this observation. Lack of a splenic filter and a deficiency in the phagocytic system are the reasons for microbial proliferation in the blood, and the lymphocytic defence mechanisms are inactive because of the absence of any focus of infection.


[Rotavirus gastro-enteritis in infants (author's transl)].

Deviation of complement antibodies were studied in 630 hospitalized infants aged from 0 to 4 years suffering from rotavirus gastro-enteritis, over a period of one year. Seroconversion was observed in 30 cases out of the 256 infants in whom 2 serological samples were taken. In 29 cases out of 30, these rotavirus infections occurred in infants under 18 months of age, and they were all seen during ther period from november to march, rotavirus being responsible for one third of the gastro-enteritis cases. A serological study according to age-group in 640 infants gave positive results in 75 per cent (1st semester), 68 per cent (2nd semester), 75 per cent (2nd year), 78 per cent (3rd and 4th years).


[Sulindac suppositories: treatment of pain in osteoarthritis (author's transl)].

Thirty one patients with osteoarthritis (29 hips, 16 knees) were submitted to a treatment with sulindac at a daily dose of 200 mg bid suppositories during four weeks. This trial showed that the treatment brought relief of pain in the majority of patients. Compared with others previously prescribed drugs, sulindac was more effective (72%). Sulindac suppositories were well tolerated; only three drop-out because side-effects (gastro intestinal tract: 2, skin 1) have been reported. Sulindac suppositories tolerance was reported as good.


[Dehydratation secondary to infantile acute diarrhea. Physiologic basis and management of parenteral rehydration (author's transl)].

It is advisable to plan the treatment of every patient according to his clinical and eventually biological data, in order to enhance the efficacy and to lessen the risks of rehydration. This paper begins with a brief review of physiological data and clinical symptoms which make the basis to evaluate the needs of each patient in water and electrolytes. The second part gives some rules of management of the parenteral rehydration, depending on the degree and the type of fluid disturbance either hyper, or iso or hyponatraemic dehydration.


[Measurement of blood chloroquine concentrations during neuromyopathies and toxic retinopathies (author's transl)].

Blood chloroquine concentrations were measured in 5 patients having complications related to this treatment. No significant differences were noted when compared to controls. Further studies are required however before drawing any definite conclusions. The persistence of fairly high residual levels, several months after stopping treatment, is evidence of chloroquine retention in these patients.


[A case of autochthonous leprosy (author's transl)].

A case is reported of autochthonous leprosy in a French patient who had never lived in an endemic zone. The disease was of the lepromatous leprosy type and the liver, spleen, skin nerves and muscles were affected. Characteristic findings were Hansen's bacillus in nasal scrapings, a deficiency in cellular immunity, and the presence of cryoglobulins and circulating immune complexes. Autochthonous leprosy which has not been imported, and without signs of direct contagion, appears to be exceptionally rare. The authors review the clinical forms of leprosy and immunological findings.


[A differential diagnosis of sural phlebitis: popliteal cysts. Value of ultrasonography (author's transl)].

Two cases are reported of popliteal cysts simulating sural phlebitis, one in a patient with lupus, the other during the course of rheumatoid arthritis. Diagnosis is based upon the following signs: sudden onset of pain, sometimes after effort, and in the knee rather than in the calf, and more especially ecchymosis occurring in the internal supramalleolar region. The decision as to whether anticoagulant treatment should be instituted must be based on the certitude of the diagnosis, and this can be obtained in an atraumatic manner by ultrasonography of the popliteal fossa as shown by iconography.


[Prevention of stress ulcers with sulpiride (author's transl)].

Stress ulcers or hemorrhagic lesions of the digestive tract may arise after multiple or cranial trauma, burns, frostbite, severe operations or intensive care treatment, respiratory of renal failure, or any other severe disorder affecting the body. The risk of a stress ulcer accurring varies from 10 to 50% according to the severity and number of factors involved. Sulpiride was studied to assess its preventive value, in 50 high-risk patients being treated in an intensive care unit for medical or surgical conditions. The dosage was 3 injectable ampoules daily during the whole period of intensive care treatment. Control investigations (endoscopy, gastric aspiration, autopsy in case of death) were carried out in all patients. No gastro-intestinal erosions or ulcers developed in any of the 50 patients, and no signs of intolerance were reported.


[External carotid arteriography in Horton's disease. A report on 11 observations (author's transl)].

Highly selective angiography was used to study eleven cases of Horton's arteritis. The results showed the presence of segmental vascular abnormalities which, though mainly affecting the temporal artery region, were also present in that of the internal maxillary artery. This examination procedure can be of great value by assisting the surgeon in his choice of biopsy sample, which is essential for diagnostic purposes.


[The lateral atlantoaxial joint involvement in the rheumatoid arthritis. Report of ten cases and review (author's transl)].

An analysis of ten recent observations of lateral arthritis of C1-C2 during the course of rheumatoïd arthritis. This lesion, which is not rare, has charactéristic symptoms: localized pain together with occipital (Arnold's) neuralgia and specific blocking of head rotation towards the afflicted side. Frontal per-oral radiography shows joint line lesions most often unilateral, and a displacement of C1 towards the non afflicted side with pseudoinclination of the odontoïd process towards the afflicted side. Sometime more destructive lesions of the lateral masses of the atlas give them a triangular form and this may result eventually in an upwards "vertical" displacement of the odontoïd. The pain usually subsides in a few weeks after a conservative treatment with or without temporary immobilisation by a light removable cervical collar but the loss of the homolateral rotation of the head persists. Besides occipital (Arnold's) neuralgia, there seems to be no other neurologic complications; if they follow, it is due to an associated anteroposterior displacement.


[Headache following intrathecal therapy in acute leukemia: trial of tiapride as a symptomatic treatment (author's transl)].

11 patients experienced 40 intrathecal injections of cytotoxic drugs during the treatment of acute leukemia. Tiapride was used as a preventive or curative therapy for headache. Results were found excellent or good in 70% of cases. Frequency and intensity of headache were reduced by half. Tiapride seems more effective in early headache than in cephalalgia occuring later.


[Parenteral hyperalimentation in the treatment of esophageal, gastric and intestinal fistulas (author's transl)].

Parenteral hyperalimentation and complete bowel rest reduce fistula output, and permit sufficient caloric and nitrogen intakes needed for healing. It corrects metabolic and nutritional deficiencies due to digestive fistulas, and allows spontaneous closure of fistulas in two out of three patients. If spontaneous healing is not obtained after six weeks of parenteral alimentation, surgical treatment may be undertaken more safety, as the patient will be in better nutritional condition.


[Myospherulosis: a riddle asked by strange bags of marbles. A report of four cases (author's transl)].

Four cases of "myospherulosis" are presented with a review of the thirty cases previously reported in the litterature. The disease is characterized by clusters of spherules, surrounded by a thin membranous bag, within a multicystic reaction of muscular and subcutaneous tissue or of paranasal sinuses. The actual nature of these spherules still remains unknown. Several pathogenic hypothesis are suggested.


[Developed carcinomas of the lower oesophagus with peptic lesions (author's transl)].

The authors report seven cases of carcinomas of the lower oesophagus with peptic lesions. Based on clinical, endoscopical and histological criteria, they point out these peptic lesions preceded the carcinoma in all the cases certainly or very probably. They emphasize at last two cases where the peptic lesions after a strict supervision during many years, gave place, in spite of it all, to a cancerous transformation.


[Study of morbidity according to age and sex in adult persons deceased at hospital (author's transl)].

Studying morbidity according to age and sex in persons decreased at hospital, the authors point out that many illnesses grow in frequency with age. Very often too, illnesses grow in number with age; but this is not constant. At last, this study allows to state the behaviour of old people before illness and the influence of senescence on the terminal evolution.


[Anatomical lesions of the liver and oral contraceptives (author's transl)].

Based on two cases, the authors recall the anatomical lesions of the liver occurring at times in women using oral contraceptives: jaundice, benign tumors, vascular lesions; and they emphasize more particularly the vascular lesions and their relation with oral contraceptives.


[Granular cell myoblastoma or Abrikosov's tumor of the esophagus].

Granular cell myoblastoma or Abrikossoff's tumor of the esophagus are exceptional: fiveteen cases have been described in the literature. In this work we present the following case: discovery of a sub mucosal tumor during a systematic fibroscopic examination of an anemix patient. Only histological examination was able to make the diagnosis.


[The Vaugirard hospital: radio-anatomo-clinical confrontations (author's transl)].

Since its foundation in the beginning of this century, the Vaugirard hospital of which the origin is briefly recalled, found its way towards digestive surgery and gastroenterology. This induced the creation, 35 years ago, of the Vaugirard Radio-anatomo-clinical Confrontations, only dedicated to digestive pathology.


[Neurological follow-up of glioblastomas treated by chemotherapy. Therapeutical incidences (author's transl)].

The authors describe the essential neurological complications observed during the follow-up of glioblastomas treated by sequential chemotherapy. They were studied on the basis of clinical, isotopical, CT scanner and or anatomical data. The most frequent complications are: epilepsy, acute neurological deficiency and intracranial hypertension. The diagnostic significance of the complications are discussed. Usually, they expresse a tumour extension. However, the recurrence presents varied aspects. It can be infiltrating and extensed, multifocal, focal, cystic ou pseudocystic. In the majority of cases the morphological, topographical and evolutional characters can determine the therapeutical attitude.


[Three cases of renal artery's aneurysm with high blood pressure (author's transl)].

The authors report three cases of renal artery's aneurysm that caused high blood pressure. Their surgical treatment led to the cure of this high blood pressure. In one case, were applied ex situ surgery's procedures but with local replantation. Then, the authors argue the connexions between renal artery's aneurysms and high blood pressure as well as the indications for their treatments.


[Major hepatic resections. 74 home cases and general review (author's transl)].

Reporting 74 home cases and data of recent litterature, the Authors try to take stock of major hepatic resection in 1978. Technical difficulties are recalled. The control of vena cava and major hepatic veins remains critical. So are blood coagulation troubles (6 cases). The technical choice amounts of either the ruled hepatectomy first described by J. L. Lortat-Jacob, or the finger-fracture technique. The latter should be preferred in resection for trauma (faster with healthy liver and on unchanged anatomy). In any other cases, we prefer the ruled technique. So do many authors. Vascular isolation techniques should deserve a larger use cross-clamping techniques are available for huge posterior tumours, in normovolhemic and healthy hearted patients. This procedure is fairly advisable in case of significant hemorragic risks. It might increase the resecavility rate (27). Tight monitoring and heavy material means make it available only in specialized centers. Intra-caval shunts, first conceived for caval and hepatic wounds, are an isolation procedure of choice in trauma and hypovolhemy. A larger experience should make the indications more precise. Advance in hepatectomy should reduce morbidity and mortality rates to those of other major digestive surgery. The post-operative course is studied; hemorrhagic and septic complications head the list. The biliary drainage is discussed: its indications should be consistantly reduced. Coagulation troubles and metabolic problems are analyzed advance in hepatic regeneration is pointed out. Indications of major hepatic resections are studied. It seems they should be spead out.


[Neonatal diagnosis of hypothyroidism by measurement of TSH levels: results in a series of 1880 cases from the University Hospital Center in Caen (author's transl)].

Early substitutive hormonal treatment for congenital hypothyroidism is the main factor affecting the prognosis of mental abnormalities. Therapy should be instituted in the first few weeks of life but clinical diagnosis is usually very difficult at this stage and biological criteria have to be used as a basis for establishing the diagnosis during the neonatal period. For this reason, TSH levels were measured in 1880 babies on the 4th day of life. This enabled a diagnosis of thyroid agenesia to be made in a case where no tangible clinical signs were present, and treatment could be started on the 12th day of life. Furthermore, two cases of hypothyroidism from iodine overdosage during amniography were discovered and early treatment instituted. The results of this study, which was limited to only one maternity unit, demonstrate the value of systematic diagnostic procedures for congenital hypothyroidism. It also underlines the danger of iodine overdosage during foetal life which could contra-indicate the use of amniography.


[Urinary tract infection in urology (author's transl)].

We studied the rate of infection in 144 pre- and post-operative patients. Before intervention the rate is 21,5% and in the post at the discharge of the patient from the hospital, the rate is 28%.


[Immunologic disturbances in psoriatic arthropathy (author's transl)].

It was observed in 51 cases of psoriatic arthropathy (PA) an increase of blood IgA and a decrease of IgM, a not significant rise of the level of circulating immune complexes, a positive Waaler-Rose reaction in 9.7% of cases and the presence of antigammaglobulin factors (generally of IgG type) in 55,5% of studied patients. Moreover, it was noted a significant decrease of T lymphocytes as detected by E and "active" E rosettes, of EA-gamma rosettes (ox erythrocytes) and an increase of the percentage of high avidity Fc-gamma receptor bearing cells. Lymphocytes responses to mitogens were normal or slightly decreased for Concanavalin A. No correlation was found between the immunological data and the clinical features.


[Idiopathic neuroarthropathy in a woman (author's transl)].

The authors report a case of idiopathic and sporadic neuroarthropathy in a 53 year - old woman and point out the rarety of the disease in women unstead of familial Thevenard disease and diabetic neuroarthropathy.


[HLA and amyotrophic lateral sclerosis (author's transl)].

52 patients with amyotrophic lateral sclerosis and 300 normal subjects were tested for 33 HLA-A, B, C antigens. We did not observe any statistically significant difference in antigenic frequencies between the two groups. The absence of association with HLA in amyotrophic lateral sclerosis is a distinction with multiple sclerosis, which is associated with several HLA antigens.


A pragmatic approach to mental health aftercare and partial hospitalization.

Over recent years, there has been increased attention to providing viable community-based alternatives to inpatient psychiatric care. Although there is increased demand for aftercare or daycare social/psychological community treatment, funding sources also mandate more clearcut and precise demonstrations of therapeutic and program effectiveness. This paper describes a pragmatic new approach to daycare for the emotionally disturbed. The central aspects of this approach are: the behavioral identification of clearcut psychosocial treatment goals, contractual negotiation of treatment plans, a skill remediation approach to treatment and objective evaluation of client improvement. By adopting practical and individually-tailored treatment goals and modalities, and by incorporating objective evaluative criteria into a daycare program's treatment components, it is possible to more accurately assess client improvement.


[Interest of percutaneous biliary drainage following percutaneous transhepatic cholangiography in certain obstructive jaundice (author's transl)].

In addition to the well-known usefulness of percutaneous transhepatic cholangiography, that procedure demonstrates a supplementary interest in certain special cases of dilated biliary tract when it is associated with a external biliary drainage; that drainage is performed by means of a method designed after Seldinger's percutaneous catheterization. That single two-step procedure is a sparing transient palliative policy for certain types of obstructive jaundice; it also permits a more comfortable survival when surgery cannot be achieved.


Genetics of cell fusion: human chromosome 10 assignment of a gene (FUSE) that promotes polykaryocyte formation.

FUSE, a human gene which promotes polykaryocyte formation, has been identified and examined in cocultivation assays between rat XC cells and human-mouse hybrids retaining different combinations of human chromosomes. Polykaryocyte formation was never detected when parental cells of hybrids were cocultivated with XC cells. Somatic genetic synteny analysis employing different hybrid sets demonstrated that FUSE was coexpressed with the chromosome 10 markers glutamate oxaloacetate transaminase (GOTs) and an external membrane protein (EMP-130). Cytogenetic analysis confirmed this assignment to human chromosome 10. FUSE was expressed by hybrids made with both human leukocytes and fibroblasts from several individuals, indicating the gene is found in different tissues and may be ubiquitous. Only XC cells were involved in polykaryocyte formation as demonstrated by 33258 Hoechst staining and the absence of heteropolymers between rat and cell hybrid multimeric enzymes. Evidence suggests that the gene FUSE produces a nondiffusible and noninfectious product that is associated with the human-mouse hybrid surface.


Maintenance of replication patterns in human-mouse hybrids retaining only one human chromosome.

The time of termination of DNA replication of human chromosomes in human-mouse hybrids retaining only one human chromosome was analyzed. Hybrids between SV40-transformed human skin fibroblasts and mouse peritoneal macrophages were used for these studies. Data obtained from hybrids containing only human chromosome 7 or 17 were compared with data from related hybrids containing additional human chromosomes. When either human chromosome 7 or 17 was present alone, it terminated replication at the same stage of the S phase as in hybrids in which other human chromosomes were present (relative to the time of termination of replication of the mouse chromosomes). In comparing the hybrids containing single human chromosomes, it was found that chromosome 17 terminated replication much earlier than chromosome 7. Therefore, the relationship between the replication times of these chromosomes normally observed in human cells was maintained in the hybrids in the absence of all other human chromosomes. The results also indicate that the presence of SV40 gene sequences in chromosomes 7 and 17 did not alter the relative times of termination of replication of those chromosomes.


[Ibuprofen in osteo-articular (author's transl)].

The authors point out the good results which are obtained in osteo-articular pathology, in particular vertebral, with ibuprofen (Brufen 400). Providing that a sufficient dosage is given (1 600 mg - 2 400 mg per day), an obvious and fast favourable effect is noticed in 75% cases. According to these results, tolerance is quite satisfactory.


Egg drop syndrome, 1976 (EDS'76).

A description is given of the new clinical condition in fowl now known as EDS 76. This is characterised by the production of thin shelled, soft shelled and shell less eggs by apparently healthy birds. The effects on egg production are seen around 30 weeks of age and are seen either as an apparent fall in production or as a failure to obtain predicted production targets. Haemagglutinating viruses have been isolated from these flocks and evidence from experimental and field investigations suggest these are the aetiological agents of EDS 76. Biochemical and biological studies indicate that these viruses are duck adenoviruses. Epidemiological evidence suggests the virus is egg transmitted and that lateral spread between flocks is not important if care is taken whilst bleeding and vaccinating flocks. It is postulated that this virus may have been introduced into flocks by the use of a contaminated vaccine. Control in Northern Ireland has been by eradication of the virus from the basic breeding stock.


A biochemical and ultrastructural comparison of Triton X-100 models of normal and transformed cells.

We have compared the two-dimensional gel profiles of Triton models of normal rat kidney (NRK) cells and their Kirsten viral transformant, 442. Several protein differences were detected. The models of the transformed line lacked five acidic polypeptides and possessed a much higher intermediate filament to actin ratio. Scanning microscopy reveals significant ultrastructural differences in these models, with the NRK line exhibiting a much more filamentous structure. In addition, nuclease treatment of NRK models causes a dramatic change in their scanning image while the 442 models are unaffected. Nuclease treated models lack microfilaments and appear to contain only intermediate filaments, although actin is still a prominent protein constituent.


Vitamin D-induced coronary atherosclerosis in normolipemic swine: comparison with human disease.

Coronary atherosclerosis developed in normolipemic swine fed a basal ration supplemented with 125,000 IU, 62,500 IU and 31,250 IU of vitamin D3/kg of diet for 3 months and subsequently only the basal ration for the following 3 months. Lesions consisted of intimal atheromata and calcified internal elastica and caused luminal narrowing. The incidence of atherosclerotic lesions was proportional to the vitamin D3 doses. The present experimentally induced lesions had many morphological features resembling those in coronary arteries from human subjects.


A simple method to determine adenylate cyclase activity in isolated single nephron segments by radioimmunoassay for succinyl adenosine 3',5'-cyclic monophosphate.

A simple method to determine adenylate cyclase activity in isolated single nephron segments is described. Segments of the proximal convoluted tubule or the cortical collecting tubule were isolated from rabbit kidney slices pretreated with collagenase. After the tubule membranes were made permeable by adding hypotonic medium and freezing-thawing, each sample was incubated at 30 degrees C for 30 min in a medium containing ATP and theophylline. Generated cAMP was succinylated and served for radioimmunoassay. Addition of the incubation medium did not interfere the radioimmunoassay. Recovery of added cAMP was 96%. In the proximal convoluted tubule, either 8 mM NaF or 1 U/ml parathyroid hormone (PTH) markedly stimulated adenylate cyclase activity, but 1 mU/ml arginine vasopressin (AVP) did not. By contrast, in the cortical collecting tubule, either 8 mM NaF or 1 mU/ML AVP markedly stimulated adenylate cyclase activity, but 1 U/ml PTH did not. These data imply that this method is sensitive enough to detect either specific or nonspecific response of adenylate cyclase activity in single nephron segments.


A lymphoblastoid cell line from an adenosine deaminase deficient patient established by Epstein-Barr virus.

Lymphoblastoid cell lines from a patient with adenosine deaminase (ADA) deficiency and his parents were established by Epstein-Barr virus (EBV). ADA activity in the lymphoblastoid cells from the patient was not detectable, while the enzyme activity in the cells from his parents was approximately a half level of the controls'. No inhibitor to ADA could be detected in the lymphoblastoid cells from the patient.


Neuromuscular blocking property of minocycline in the rabbit.

The neuromuscular blocking property of minocycline hydrochloride (MNC) was studied in 12 rabbits. In 2 of 6 animals, MNC, 60-160 mg/kg, alone caused a decrease in twitch tension. During partial neuromuscular blockade produced by a continuous infusion of pancuronium, the intravenous administration of MNC, 20--60 mg/kg, resulted in a dose-dependent decrease in twitch tension in 6 animals. MNC-induced or combined MNC-pancuronium-induced neuromuscular blockade was antagonized by calcium or by neostigmine.


Free lung cell response after combined exposure to cigarette smoke and industrial dusts.

Guinea pigs were acutely exposed to different airborne dusts and freshly generated cigarette smoke. The effect was evaluated by counting the number of free lung cells using a lavage method. An exposure to MnO2 and smoke on the same day caused an increase in the number of leukocytes 24 h thereafter. By increasing the time interval between the MnO2 and smoke exposure, the effect gradually disappeared. Al2O2 or SiO2 also caused an increase in the number of leukocytes, whereas TiO2 had no effect. The pathogenesis behind the reaction and the epidemiological implications are discussed.


Increased aryl hydrocarbon hydroxylase and prolyl hydroxylase activities in lung organ cultures exposed to benzo[a]pyrene.

Exposure of neo-natal rat lungs in organ culture to 10--25 microM benzo[a]pyrene (BaP) elevated the activities of aryl hydrocarbon hydroxylase (AHH) and prolyl hydroxylase (PH). Pyrene, a non-carcinogenic hydrocarbon did not elicit this response. Prolyl hydroxylase is an indicator of collagen synthesis and increased PH activity in the lungs reflects increased collagen synthesis. Our studies suggest that the earliest events in BaP-induced lung injury may include altered collagen metabolism.


[NAD+ synthesis in the isolated kidney cell nuclei of dogs after the intravenous administration of amphotericin B].

A study was made of the synthesis of nicotinamide adenine dinucleotide (NAD+) in the nuclei of kidney cells of dogs under normal conditions and upon the effect of the polyenic antibiotic amphotericin B. An active NAD-pyrophosphorylase has been found in the nuclei of kidney cells. It has been established that a intervenous introduction of amphotericin B stimulates NAD+ production. Amphotericin B also causes a decrease in the amount of histones in the nucleus. In the case of the nuclear membrane damage by a non-ionic detergent Triton X-100, no increase in the synthesis of NAD+ has been observed in the nuclei of kidney cells of animals treated with antibiotics, as opposed to the control ones. Under discussion is a question of a possible mechanism of the effect of polyenic antibiotics on the synthesis and metabolic activity of NAD+.


Natural antilymphoma antibodies in C3Hf mice serum: lack of identity with autoimmune and anti murine leukemia virus antibodies.

Absorption experiments on C3Hf normal mouse sera followed by cytotoxic tests on EL4 lymphoma cells were done to investigate a possible identity between natural antilymphoma antibodies (NAA) and various types of autoantibodies known to be present in normal mouse sera. Single C3Hf normal sera were also tested both by cytotoxicity on EL4 cells and by radioimmune precipitation assay (RIP) on 125I-labelled AKR ecotropic virus to ascertain whether or not viral antigen are the target structures of the NAA activity. The study provides evidence that NAA coexist with autoanticorpal and antiviral activities although they are distinct entities.


[Viable cells from human renal cell carcinoma: isolation procedure and analysis of hormone sensitivity (author's transl)].

An enzymatic procedure for the isolation of metabolically active tumour cells from human renal cell carcinoma is described. The cells were suspended by a multistep incubation procedure of the tissue in the presence of collagenase (10 mg enzyme/g tumour wet weight) dissolved in a calcium-free buffer solution. About 90% of the isolated tumour cells were viable, as judged by routine trypan blue staining. Electron microscopic examination revealed tumour cells in various stages of dedifferentiation. The cells had retained their capability of protein synthesis. In short term experiments the effects of 17 beta-oestradiol and progesterone on the incorporation of [U - C] L-leucine into cellular proteins was studied; Progesterone was found to exhibit a slight tumour antianabolic or catabolic action. A 17 beta-oestradiol-dependent modulation of the rates of protein synthesis was not observed.


Percutaneous 17 beta-estradiol in treatment of cancer of prostate.

A natural estrogen, 17 beta-estradiol, was given percutaneously to 21 patients with untreated cancer of the prostate. The follow-up lasted three to six months, and the results of the survey were encouraging. The hormonal controls showed good plasma diffusion of estrogen, a significant drop in plasma testosterone, and decreased hypophyseal secretion as shown by lower follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. Triglycerides and very low density lipoproteins (VLDL) which are considered to be good indicators of cardiovascular risk were unchanged.


Peripheral neuropathy and myopathy. An experimental study of rats on alcohol and variable dietary thiamine.

The effects of variable dietary thiamine concentrations (deficient, normal, surplus) on the development of alcoholic neuromyopathy in rats exposed for 36 weeks to 10-25% (v/v) ethanol or water (control group) as the sole drinking fluid were studied by histological and electrophysiological methods. Abnormalities in the structure of the sciatic nerve (phagocytosis, myelin abnormalities, increase in nonspecific cholinesterase activity) and tibial muscles (angular atrophic fibers, group atrophy, fibre necrosis) developed more frequently in animals on diets deficient in thiamine than in animals on diets with normal or surplus thiamine, and more frequently in animals drinking alcohol and water than in those drinking water alone. No differences were observed between the different groups in the number of perivascular sympathetic nerves, in the motor nerve conduction velocities and in the muscle fibrillation potentials. Thus, thiamine deficiency, established as a significant reduction of red blood cell transketolase activity, seems to have a deleterious effect on the peripheral nerves and muscles. The effect is enhanced by the simultaneous consumption of ethyl alcohol.


Clonal proliferation of lymphoid and myeloid progenitor cells in patients with hematological abnormalities.

Myeloid and lymphoid stem cell colony formation (GM-CFU) and L-CFU) was studied in patients with lymphoproliferative diseases, aplastic anemia and other hematological abnormalities. Most patients with acute lymphatic leukemia had low number of L-CFU with decreased or normal GM-CFU, while in Hodgkin's disease and chronic lymphatic leukemia L-CFU growth was very poor with only minor abnormalities of GM-CFU formation. Aplastic anemia was characterized by a decreased GM-CFU and normal L-CFU. Coculture studies suggested that a diminished colony formation may be linked to circulating lymphocytes that inhibit L-CFU as well as the reduction in number of precursor cells.


[Tissue respiratory enzymes in the rat liver in acute blood loss].

An increase in activity of several dehydrogenases of tricarboxylic acid cycle (NADP-dependent malate dehydrogenase, alpha-ketoglutarate dehydrogenase) was observed in rat liver tissue under conditions of acute hemorrhage. The enzymatic activity was slightly higher in the group of animals with relatively prolonged life-time as compared with those, which lived less than 4 hrs. Activity of cytochrome oxidase was inhilited in the both groups of animals (by 27% and 29%, respectively). The less distinct decrease in both temperature in the group of animals with prolonged life-time might maintain the rate of Krebs cycle substrates oxidation. Activation of respiration in liver tissue under conditions of the hemorrhage is considered as a compensatory reaction tending to improve oxygen utilization in hypoxia. At the same time, inhibition oy cytochrome oxidase demonstrates the impairment of electron transport and decreased rate of energy production in liver mitochondria.


[Effect of chemical hepatic carcinogens and noradrenaline on the nucleoside phosphokinase activity of liver cells].

Distinct increase in activity of uridine kinase and pronounced decrease in thymidine kinase activity were observed in cell-free extracts of rat liver tissue at early stages of hepatocarcinogenesis caused by administration of N-nitrose diethylamine and 2-acetyl aminofluorene. Exogenous noradrepaline did not affect the altered activity of thymidine kinase but stimulated the effect of N-nitrose diethylamine and lowered the effect of 2-acetyl aminofluorene on the urindine kinase activity. Adrenergic neurotransmitters appear to influence the cell proliferation due to modification of the enzymes participating in the synthesis of nucleic acid precursors.


[Effect of carbostimulin and its mixture with vitamin D3 on the mineralization process of the bone callus in rabbits].

Mineralization of rabbit bone callus was studied within 15 days after resection of the upper part of radius bone inder conditions of treatment with carbostimuline and its mixture with vitamin D3. Content of calcium in the bone regenerate was increased by 40.8% after administration of carbostimuline and--by 70.5% after treatment with mixture containing vitamin D3. These preparations caused only slight effects on the phosphorus content. Dry residue in the regenerate os f animals, treated with the preparations, was increased approximately 2-fold (43% and 23%, respectively, p less than or equal to 0.001) as compared with control group. Content of citric acid was distinctly higher in the bone tissue of the treated animals. Within 15 days after the operation content of sialic acids wanormalized in blood serum of the animals. The data obtained were corroborated by X-ray and histologic examinations.


Conceptual and methodological considerations towards the development of computer-controlled research on the electro-physiology of sleep.

A critical discussion of the visual scoring approach to the measurement of sleep electrophysiology details some theoretical shortcomings of that procedural model. An alternative approach employing high-speed, general purpose digital computers is then presented. It is argued that the measurement potential of computers is barely tapped by using computers to score sleep stages and the advantages of collecting data which are suitable for parametric and multivariate statistical analysis are described. Researchers are urged to include detailed reports on their procedural choices along with a discussion of the methodological implications of these procedures. Examples of computer collected data are presented along with a description of some simple data reduction strategies.


[Comparative study of the hemolytic action of group D vitamins].

Hemolytic effects of the vitamins of the D group (ergocalciferol - D2, cholecalciferol - D3, and 1 alpha-hydroxycholecalciferol - 1 alpha-OH-D3) were compared using rat erythrocytes. The latent period of hemolysis, caused by 1 alpha-OH-D3 was approximately 3-fold shorter as compared with the hemolysis caused by D2 or D3. Apparent values for energy of activation of hemolysis, estimated at 30-45 degrees, constituted for D2 - 23.2 kcal/mol, D3 - 25.3 kcal/mol, 1 alpha-OH-D3 - 13.1 kcal/mol. Despite the higher hemolytic activity, the rate of 1 alpha-ON-D3 autooxidation was distinctly lower than that of D3.


[Polygraphic study of nocturnal sleep in three degenerative diseases: ALS, oligo-ponto-cerebellar atrophy, and progressive supranuclear palsy].

A polygraphic study of nocturnal sleep was carried out on 12 patients suffering from amyotrophic lateral sclerosis (ALS), 6 patients suffering from olivio-ponto-cerebellare-atrophia (OPCA) and 9 patients suffering from the Steele-Richardson disease (SR). A disturbance of sleep--if it exists--always runs parallel with the course of the disease. No disturbances were registered in the group of patients suffering from ALS, in the OPCA group a specific disease of paradoxal sleep is observed. The sleep disturbances are more global in the group of patients suffering from the SR disease. A particular electrooculogram was taken from the patients from the awakening and from the paradoxal sleep. Respiratory difficulties were registered on certain patients of each of the three groups. These sleep disturbances, registered by the polygraph, were compared with those observed on patients presenting a cortical disease.


Polygraphic analysis of sleep in dystonia musculorum deformans.

The functional state of non-specific brain systems was studied in 27 patients with torsion dystonia through a complex of techniques, which included clinical, experimental psychological and electrophysiological examination of night sleep. Changes of involved nature have been identified in the various elements of non-specific systems in different clinical forms of the disease in its early and advanced stages, which allows to consider torsion dystonia as a functional organic psychomotor syndrome in the origination of which a great role belongs to non-specific integrative systems of the brain.


Short-term effects of CHO, fat and protein loads on total tryptophan/tyrosine levels in plasma as related to %REM sleep.

The effect on plasma amino acid levels and sleep parameters of three experimental diet conditions was investigated in 12 healthy young men. A total of 71 sleep records and 715 plasma samples were analysed for %REM (TDT) and total plasma tryptophan and tyrosine respectively. The ratio of tryptophan to tyrosine was virtually the same under the fat supplement as under the nosupplement conditions. The ratio associated with the CHO load was found to be 14 per cent higher, however. A 29 per cent higher value found with the Protein load may be misleading due to the nature of the supplement used. %REM (TDT) was not found to be significantly related to any of the above conditions.


Effects of L-tryptophan on sleep onset insomniacs.

Eighteen female subjects with demonstrated laboratory sleep onset latency greater than 20 minutes for two nights participated in this double blind study of the effectiveness of l-tryptophan as a hypnotic. Standard sleep recordings were made on 10 nights over a 3 month period with lights out occurring 20 minutes after drug administration (placebo, 1 gm. l-tryptophan, 3 gms. l-tryptophan). Neither dose of l-tryptophan differed from placebo as to the amount of REM, SWS or wakefulness, but 3 gms. significantly reduced sleep onset latency on some of the nights. Those subjects with latencies longer than 40 mins. had the greatest reduction in latency with 3 gms. and also evidenced high levels of anxiety on the Taylor Manifest Anxiety Scale initially. Subjects with latency between 20 and 40 minutes appeared to receive the longest lasting hypnotic effect from the higher dose. Adaptation to the sleep lab took place across the entire 10 nights of the study. Therefore, valid comparisons between treatments in a sleep study extending over a number of nights should be made between temporally adjacent samples.


[Tracheal and bronchial cylindromas (author's transl)].

Cylindromas, characterized by its invasive growth, contain 3.7% of all adenomas of bronchial tree (160). Two of 10 cases of tumours mestastized. However, unqualified cylindromas attaching to cancers (adenoid cystic cancer) is not justified. Histological structure of cylindromas is more variable than it is described by other authors. It is proposed to differ 4 histological variants: cribrouse, trabecular, and chondroid. Histological, histochemical and electronmicroscopical analysis allowed to discover the dual character of tumour cell secretion. As to its chemical composition, the secretion of the lumen of mucous tubulae resembles the ordinary mucus, but in cribrouse nests and across trabecular periphery and solid nests it was discovered the particular (special) secretion, rich in acid mucopolysaccharides. Feyrter's observation of endocrine activity of cylindromas are not confirmed. Tissue source of cylindromas of different localizations, in particular, bronchial may be myoepithelial cells.


[Spin-lattice-relaxationtime T1 measurements of nucleosides (author's transl)].

Nucleosides and nucleotides have been investigated by means of the spin-lattice-relaxationtime T1, the measurements carried out in CDCl3 on the nucleosides adenosine (A), uridine (U) and inosine (I) indicate that the strength of H-bonding is highest in the basepair (A)--(U). The systems (A)--(A), (U)--(U), (I)--(A) and (I)--(U) however, show only a low tendency to associate. Plotting the spin-lattice-relaxationtime, of the nucleotide protons in fragments (mol weight below 40,000) originated from DNA or RNA, against increasing temperature gives a curve with a sigmoide shape and a Tm value of 80 degrees C. The average of the activation energy for the H-bonding is 18.02 KJ/mol. The investigations clearly show that the spin-lattice-relaxationtime measurements open first of all a new method for research on H-bonding, secondly it is even in the case of nucleosides and oligonucleotides, where most of the common methods fail, a way to get information about H-bonding effects.


On the possible involvement of ascorbic acid and copper proteins in leukemia. III. ESR investigations on the interaction between ascorbic acid and some transition metal ions.

The interaction between lyophilized samples of ascorbic acid and Cu2+, Fe3+ or Mn2+ has been investigated by means of ESR spectroscopy. All of the three transition metal ions form complexes with vitamin C, but only in the case of Cu2+ and Fe3+ the interaction results in a reduction of the metal ions. Cu2+ and ascorbic acid seem to form 2 : 1 complexes with an equilibrium constant of about K = 1 X 10(7) mol-1. None of these metal ion complexes exhibits, however, the ESR spectrum obtained with leukemic blood.


On the possible involvement of ascorbic acid and copper proteins in leukemia. IV. ESR investigations on the interaction between ascorbic acid and some copper proteins.

The interaction between lyophilized samples of ascorbic acid and some copper proteins (ceruloplasmin, cytochrome-c-oxidase, ascorbate-oxidase) has been investigated by means of ESR spectroscopy. The spectra obtained are identical to the one obtained with leukemic blood. The consequences of this for the molecular events occurring in cancer are discussed. The model proposed can explain the experimental findings reported thus far (such as change in spin concentration with the development of cancer, the presence of a high concentration of antioxidants etc.) as well as reconsile the two existing and seemingly contradictory hypothesis. Possible implications for lipid peroxidation and for the respiratory process are discussed.


[Identity of polystome larvae, parasites of Dicroglossus occipitalis tadpoles, on the Ivory Coast (author's transl)].

The morphological analysis of the haptorial hooklets of african Polystomatidae shows that many species of larvae parasitize the tadpoles of Dicroglossus occipitalis (Günther). These multiple infestations are in contrast to the close parasitic specificity recognized by the adult Polystomes. This difference is explained by the behaviour of the host and the notion of supplying host is introduced.


[Correlations between HSV-2-infection and precancerous condition of uterine cervix (author's transl)].

Two groups of patients were examined and compared. One of them had been made up of 113 women from whom positive cytological responses had been recorded to colposcopy, and the other included 59 women with negative findings. The titres to HSV-2-infection were higher with significance in the first group. The authors conclusion is that HSV-2 infection might be one of the risk factors contributory to carcinogenesis in the uterine cervix.


[Cytotoxic antibodies in the serum of C3H mice after inoculating them with spontaneous mammary gland tumor cells].

Complement-dependent cytotoxic antibodies against the cells of mammary tumor MMTI appeared in the blood of C3H/He and C3Hf mice at the terminal stage of tumor growth; at the same time the mice of the above-mentioned substrains showed no difference in the degree of reaction. The level of natural cytotoxic antibodies against MMTI tumor cells detected in old C3H/He and C3Hf mice significantly exceeded their level in young mice affected with tumor; however, MMTI tumor cells grew equally fast in both old and young animals. The sera of mice affected with tumor had a weak cytolytic activity against the cells of hepatoma 22a and did not affect L cells and embryonal fibroblasts. The sera were partially exhasted by spleen and renal tissues, as well as the cells of spontaneous mammary tumor obtained from syngeneic animals and were not exhausted by allogenic cells infected with Rauscher murine leukemia virus.


[Inhibitory effect of hydrocortisone and corticotropin on the self stimulation reaction].

The effect of hydrocortisone and ACTG on the frequency of self-stimulation reaction (SS) was studied. It was shown that hydrocortisone markedly suppresses the central mechanism of the positive reinforcement. SS frequency is lowered 10-15 minutes after the drug administration and recovered in one hour. The changes in the frequency of SS in response to ACTG are simular to the hydrocortisone effect, but are less intensive and in some cases depend on the location of the stimulating electrodes.


[Clinical and biochemical heterogeneity of the Lesch-Nyhan syndrome].

The screening program directed towards a detection of patients with hereditary enzymopathy allowed to reveal 8 boys from 4-14 years with the Lesch-Nyhana syndrome. Among these children 4 were studied in detail clinically and biochemically. The study demonstrated that there were different degrees of mental retardation, autoagressive or agressive behaviour. The activity of erythrocyte hypoxanthinguanine phosphoribosyltransferase (HGPRT) in 2 cases was not changed, in 1-decreased and in 1--was absent. In 1 case of a decreased activity of hypoxanthinguanine phosphoribosyltransferase there was a drastic drop in the activity of adeninphosphoribosyltransferase (APRT). The study showed that there was a double increase in the cerruloplasmin activity in the blood plasma and of the cytochromoxydase in the leukocyte mitochondria. This indicates that the genetically determined drop in the HGPRT or APRT leads to disturbances in the other links of metabolism in the organism. The clinical manifestation of the disease due to a disturbed metabolism of biogen amines in the CNS is postulated.


Protein-cationic detergent interaction. Interaction of bovine serum albumin and other proteins with alkylpyridinium bromides studied by viscosity, gel filtration and spin-label methods.

Viscosity, gel filtration and spin-labelling methods have been used to study the influence of alkylpyridinium bromides on the conformation of bovine serum albumin and other proteins. Cationic detergents cause partial unfolding of the native protein molecules. The magnitude of these changes increases with increasing length of the detergent hydrocarbon chain. When cationic detergents are added to reduced and carboxymethylated bovine serum albumin the observed changes are opposite to those found in native protein.


Metal--glutathione interaction in aqueous solution. Nickel(II), cobalt(II) and copper(II) complexes with oxidized glutathione.

The interaction of copper(II), nickel(II) and cobalt(II) ions with oxidized glutathione in aqueous solutions have been examined by spectroscopic methods. Cu(II) is the only ion which interacts with disulphide bridge and forms dimeric species containing the Cu(II)-S-S-Cu(II) unit. Ni(II) and Co(II) bind mainly with the terminal NH2 and COO- groups of glutamic acid, and the complexes formed are of nearly octahedral symmetry. At high pH, in the Co(II)-GSSG solution Co(II) is oxidized to Co(III) with the concomitant reduction of GSSG to GSH. Considerable differences were observed between the oxidized and reduced form of glutathione in the coordination ability towards metal ions.


Nucleic acid and sulphated glycosaminoglycan synthesis in the peritoneal membrane and in intra-abdominal adhesions in rat as affected by silica-induced peritonitis.

The synthesis of DNA, RNA and glycosaminoglycans was studied in the peritoneal membrane and intra-abdominal adhesions formed in rats after a single colloidal silica injection. The concentration of DNA and RNA increased from the first day of peritonitis reaching the maximum at 4--7 days in both the peritoneum and adhesions. On the other hand the synthesis of radioactive DNA and RNA from 3H-thymidine and 3H-cytidine increased during the first 12 hours and was maximal at 24 hours in the peritoneum and at 48 hours in the adhesions. Although the contents of uronic acids were maximal at 24 hours in the peritoneum and at 2--4 days in the adhesions, the maximal synthesis rate of sulphated glycosaminoglycans was observed at 5 days in the peritoneum and at 7 days in the adhesions. The difference in the uronic acid concentration and radioactivities of glycosaminoglycans was probably due to increased permeability of the peritoneal membrane and exudation. Earlier we observed that protein synthesis was maximal at 7 days and that of collagen at 3 weeks. On the basis of these and the present results it is obvious that the order of synthesis of these connective tissue components in the peritoneum after chemical peritonitis follows the pattern of tissue reaction in wound healing and in experimental subcutaneous granuloma formation. However, the activation of nucleic acid and glycosaminoglycan synthesis occurs promptly without any or with a very short lag period in the peritoneal mesenchymal tissue.


Malignant atrophic papulosis--Degos' syndrome.

A typical case of malignant atrophic papulosis is presented. The patient had had a symptomless, pathognomonic skin rash for 6 months and thereafter also multiple intestinal infarctions which caused perforations, peritonitis, and finally death. All therapeutic attempts, including intestinal resection and acetylsalicylic acid combined with dipyridamole, were in vain. Electron microscopy showed 200-250 A large virus-like cytoplasmic inclusions in the endothelial cells, without degenerative or regenerative changes, in a quite fresh papule. It was not possible to culture viruses on skin fibroblasts, but further studies of these inclusions are needed.


Restoration of oestrogen positive feedback effect on LH release by bromocriptine in hyperprolactinaemic patients with galactorrhoea-amenorrhoea.

Five mg of bromocriptine was administered for 3 weeks to 8 hyperprolactinaemic women with galactorrhoea-amernorrhoea, in whom the response of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to 100 micrograms of iv LH-releasing hormone (LH-RH) had been evaluated. Twenty mg of conjugated oestrogen (Premarin) was injected iv any day between the 10th and 12th day from the initiation of the treatment, and serum LH levels were serially determined for 120 h. Hyperresponse of LH with normal FSH response to LH-RH was observed in most patients. Bromocriptine treatment for 10 to 12 days significantly suppressed mean (+/- SE) serum prolactin (PRL) levels from 65.1 +/- 23.0 to 10.4 +/- 2.0 ng/ml, while LH (12.6 +/- 2.1 to 24.8 +/- 5.9 mIU/ml) and oestradiol (40.1 +/- 7.6 to 111.4 +/- 20.8 pg/ml) levels increased significantly. Patients on bromocriptine treatment showed LH release with a peak at 48 h after injection of Premarin. The mean per cent increases in LH were significantly higher than those in untreated patients with galactorrhoea-amenorrhoea between 32 and 96 h after the injection. The present results seem to suggest that the restoration of LH-releasing response to oestrogen following suppression of PRL by bromocriptine may play an important role in induction of ovulation in hyperprolactinaemic patients with galactorrhoea-amenorrhoea.


Corticosterone secreting adrenal carcinoma and empty sella turcica: a case report.

Pituitary adenoma was suspected in a woman of 74 with hypercorticism,hypokalaemic alkalosis and radiographically enlarged sella turcica. However, non-suppressibility of steroid excretion by high-dose dexamethasone and low plasma concentration of ACTH suggested adrenal tumour. Detailed analysis of urinary steroid excretions demonstrated unusually large amounts of corticosterone metabolites, 14.6 mg/24 h compared to a mean normal value of 0.5 mg. The basal levels of the remaining pituitary hormones were unremarkable. The patient died incidentally before a planned adrenalectomy. The autopsy disclosed an adrenal carcinoma and an empty sella turcica. The enlarged pituitary fossa was lined by a narrow rim of histological normal pituitary tissue.


Angiotensin II and K challenge following prolonged ACTH administration to normal subjects.

Twelve healthy male volunteers on a normal Na and K intake and ambulatory received ACTH (40 IU, im) twice daily for 5 days followed by 2 days of angiotensin II (5--13 ng/kg body weight/min for 60 min) or oral K citrate (30 mEq./h x 3). A discordance in the aldosterone-stimulating and pressor responses of angiotensin II was unmasked with only the latter response being positive following ACTH-induced refractoriness. K loading was a much more potent natriuretic stimulus than angiotensin II treatment. In contrast to angiotensin II, K could selectively enhance aldosterone secretion by overcoming the inhibition in secretion of the mineralocorticoid induced by prolonged ACTH exposure.


Effect of two prostaglandin synthesis inhibitors, indomethacin and acetylsalicylic acid, on plasma ACTH and cortisol levels in man.

The aim of this study was to investigate the possible role of prostaglandins (PG) in the control of the hypohtalamic-pituitary-adrenocortical axis in normal volunteers. Acute oral administration of 100 mg indomethacin (ID) or 1.5 g acetylsalicylic acid (ASA) did not alter ACTH and cortisol plasma levels. Administration of 300 mg daily ID for 4 days delayed the onset, but increased the magnitude, of the response of ACTH to insulin hypoglycaemia, while it blunted the cortisol response. Administration of 3.2 g ASA daily depressed ACTH response to hypoglycaemia leaving the cortisol response unchanged, except for a 15 min delay in onset. These results are interpreted assuming that ID and ASA chiefly acted at the pituitary and hypothalamic level, respectively, and that ID, but not ASA, interfered with adrenocortical cortisol production. Our findings support the concept, based on animal studies, that PG enhance hypothalamic CRF release and adrenocortical steroidogenesis and may restrain ACTH secretion in the pituitary.


Inhibitory effect of dibutyryl cyclic AMP on the release of calcium, inorganic phosphate and lysosomal enzymes from calvarial bones cultured for 24 hours.

The effect of N6,O2'-dibutyryl adenosine 3',5'-cyclic-monophosphate (dbcAMP) on the mobilization of calcium (Ca2+), inorganic phosphate (Pi) and lysosomal enzymes was studied in a bone culture system for 24 h using half calvaria from 6--7 day-old mice. DbcAMP inhibited spontaneous as well as parathyroid hormone-stimulated mineral mobilization. DbcAMP in a concentration of 5 x 10(-4)M also reduced the activities of beta-glucuronidase, beta-galactosidase and acid phosphatase found in the media while the activities of lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase were not affected. It is concluded that cAMP is not a stimulator but an inhibitor of bone resorption within the culture period studied (24 h) and that the cyclic nucleotide might interfere with release processes involved in bone resorption.


Urinary excretion of calcium, hydroxyproline and 3',5'-cyclic adenosine monophosphate in primary hyperparathyroidism.

Urinary excretion of calcium (Ca), hydroxyproline (Hyp) and 3',5'-cyclic adenosine monophosphate (cAMP) was measured during fasting, and in the afternoon, over a 3 day period. Twelve hyperparathyroid patients, of whom 6 were re-studied after successful parathyroid surgery, and 10 control subjects participated, and were maintained on a collagen free diet for the duration of the study. Expressed as creatinine ratio values, Hyp was significantly higher in the morning than during the afternoon, whereas the Ca excretion pattern showed low morning and high afternoon values for all groups. cAMP excretion did not change during the two sampling periods. Large day to day variations for each parameter were observed in the individual patient. The value of cAMP measurements in the diagnosis of primary hyperparathyroidism was confirmed. The results may imply that a diurnal variation in Hyp excretion exists in primary hyperparathyroidism and that food intake produces a suppression of Hyp excretion, possibly secondary to suppression of parathyroid function or, in our view, to increased calcitonin excretion.


Imparied cyclic-AMP response to thyrotrophin in congenital hypothyroidism with thyroglobulin deficiency.

A 19 year old man had congenital hypothyroidism and severely retarded development. His thyroid gland was not enlarged and laboratory findings included low serum concentration of T4 (2.8 microgram/100 ml) and T3 (16 ng/100 ml) with a high level of TSH (52 microU/ml) that rose to 192 microU/ml after TRH. 131I uptake by the thyroid was normal (41.5% at 24 h) and did not show a normal increase after exogenous TSH administration (49.5% at 24 h). The perchlorate discharge test was negative and no antibodies against thyroid antigens were found. Studies on the biopsy specimen revealed low iodide trapping by the thyroid slices and no formation of cyclic AMP after TSH was added to the medium. The endogenous TSH of the patient was biologically active increasing cyclic adenosine monophosphate c-AMP concentration in normal thyroid slices. No thyroglobulin was found in the thyroid tissue either by immunological or ultracentrifugational methods. An increased proportion of iodoalbumin was present in the serum. We postulate that the fundamental defect in this gland is an impaired generation of c-AMP by the defective thyroid cell and deficiency of thyroglobulin formation resulting in inadequate thyroxine and triiodothyronine synthesis.


Adenyl cyclase activity in human thyroid plasma membranes from normal human thyroid tissue and thyroid adenomas.

The adenylcyclase (AC) activity of crude human thyroid plasma membranes were studied in some detail and conditions for optimal cyclic AMP-production established. Membranes from eight "cold" and two "hot" thyroid adenomas were investigated and compared to membranes from corresponding normal, paranodular tissues. The investigated membranes were found to contain similar basal AC activities, which were stimulated three to five times with TSH and 20--30 times with fluoride. Further, no difference in the TSH-sensitivity of AC from normal and "cold" adenomas could be detected. Thyrotrophin 0.02 mU/ml caused a measurable and 0.15 mU/ml a half-maximal stimulation of the cAMP-production. The data indicate, that disturbances of thyroid hormone production characteristic of thyroid adenomas, are not caused by alterations of the TSH-AC system and suggest that in a thyroid cell the degree of thyroid hormone synthesis do not alter the amount of plasma membrane-bound adenylcyclase.


Interaction of [125I]LH-RH and other oligopeptides with plasma membranes of rat anterior pituitaries.

The specific binding of [125I]LH-RH to isolated plasma membranes of rat pituitaries was investigated. The binding process was found to be highly specific, temperature-dependent and saturable. The dissociation constant as caluclated by three different methods was approximately 1.3 . 10(-8) M, indicating a single type of binding sites. Maximal binding capacity was 1 . 10(-12 moles/mg protein (= 2 ng LH-RH/pituitary gland), and the number of binding sites was calculated to be 6 . 10(11) per mg membrane protein (=1 . 10(10) binding sites/pituitary gland). When diluted with ice-cold buffer the dissociation of specifically bound LH-RH occurred very rapidly (half-life 3.17 min) with a rate constant of 0.219 min-1. The dissociation process followed first-order kinetics. Specificity of binding was demonstrated by dose-dependent competition of unlabelled LH-RH, the highly potent analogue D-glutamine-(cyclohexyl)6-LH-RH-nonapeptide-ethylamide and the fragment of an analogue (6-D-Ser(TBu))-LH-RH-(3-9)-heptapeptide-ethylamide with the binding [125I]LH-RH, while angiotensin I, II, oxytocin and bacitracin did not compete. The affinities of LH-RH and the analogue to the binding sites of the pituitary plasma membranes were not consistent with the respective biological activities.


Further studies on hypothalamic-pituitary-testicular function in old rats.

The dysfunction of the hypothalamic-pituitary-gonadal axis in old age was studied in 24-month old male Wistar rats which were compared with 3-month old animals. The hypothalamic LH-RH content and the pituitary LH were significantly lower in the old than in the young adult animals. The plasma concentrations of LH and testosterone were significantly higher in the young rats. The primary cause of these age-dependent changes probably is a hypothalamic dysfunction. When isolated Leydig cells of young and old rats were incubated in vitro, the testosterone secretion per cell was significantly smaller in old than in young cells with as well as without HCG stimulation. In vivo stimulation of rats by iv injection of biologically active iodinated hCG revealed that the intratesticular uptake of the gonadotrophin was not different in young and old rats. The testosterone response, however, was significantly reduced in old age. An in vitro "desensitisation" experiment in which the LH receptor capacity was artificially reduced demonstrated that the 40% reduction of receptor capacity in old testes as described earlier will not impair the testicular uptake of gonadotrophin from blood. Repeated injection of hCG results in equally elevated testosterone concentrations in young and old rats.


[Phenoloxidase and peroxidase activity in presens of different effectors (author's transl)].

Small gut of the white rat was sectioned by the cryostat in slides of 10 microns and following effectors were investigated: KCN, sodium-diethyl-dithiocarbamate (DDC), NaF, sodium acetate, sodium pyruvate, 0.1 N HCl, 0.1 N NaOH, NaN3, and copper sulfate. Phenoloxidase is completely inhibited by DDC and HCl, incompletely by pyruvate and NaN3. Peroxidase also is completely inactivated by HCl and incompletely by NaN3. DDC has no effect on peroxidase, because a precipitate is formed. Neither of both enzyme activities is inhibited by KCN. In presence of KCN and copper sulfate an unspezific colouring of the tissue resulted in the phenoloxidase proof. Non of the investigated effectors is suitable to differentiate between phenoloxidase and peroxidase in histochemical investigations.


Abnormal fat metabolism in chronic renal failure.

The serum triglyceride and cholesterol levels, the cholesterol and triglyceride concentrations in the lipoprotein fractions, as also postheparin lipoprotein-lipase activity (PHLA) were determined in 18 haemodialysis-patients with chronic renal failure. Hypertriglyceridaemia and hypocholesterolaemia were found together with increased VLDL- and LDL + HDL-triglyceride and decreased HDL-cholesterol concentrations. At 10 min after administration of heparin, enzyme activity was normal, at 20 min it was abnormally decreased.


[Angiotensin converting enzyem (ACE) - a blood chemistry parameter in the diagnosis of sarcoidosis].

Serum angiotensin converting enzyme (ACE) activity was studied in 50 patients with sarcoidosis (39 active, 11 inactive sarcoidosis), as well as in 50 control patients (34 chronic lung diseases, 9 Hodgkin-disease, 7 rheumatoid arthritis). There is a significant difference (p less than 0.001) of ACE-activity between sarcoidosis patients and controls, and between active (without steroid treatment) and inactive sarcoidosis. Steroid treatment apparently lowers ACE-activity in sarcoidosis, however, without evidence for clinical improvement. Increased ACE-activity was also found in a patient with primary biliary cirrhosis.


Plasma HDL cholesterol in epileptics with elevated triglyceride and cholesterol.

Due to the metabolic changes induced, e.g. in the liver by anti-epileptic drugs, the significance of high serum triglyceride and cholesterol in epileptics was studied and the plasma HDL cholesterol level was compared in 190 epileptic patients with elevated or normal triglyceride and cholesterol, with the corresponding values in 43 healthy subjects. One-third of the epileptic patients showed elevated plasma HDL cholesterol levels. Female epileptics had higher plasma HDL cholesterol than the normolipidemic healthy subjects. Epileptics with elevated triglyceride or a combination of elevated triglyceride and cholesterol had a lower plasma HDL cholesterol level than normolipidemic patients with epilepsy. HDL cholesterol level in epileptics with high serum cholesterol did not diverge from the level in epileptics with normal serum triglyceride and cholesterol. The results show significant differences of plasma HDL cholesterol between epileptic patients and normolipidemic healthy controls on one hand, and between epileptics with altered and epileptics with normal serum lipid levels on the other. The findings suggest that the increase of plasma HDL cholesterol level in epileptics undergoing anticonvulsant treatment is influenced by endogenous triglyceride metabolism.


Pulsatile tinnitus and therapeutic embolization.

Fifteen patients with disabling pulse-synchronous tinnitus were investigated with super-selective angiography demonstrating an arteriovenous malformation in 8 cases, chemodectoma of the jugular bulb in 3, and a local arterial stenosis in one case. In 12 of these cases the murmur could be registered objectively, while in the 3 cases with a negative angiographic finding no such murmur could be heard, an observation which may be of importance when selecting patients for further angiographic examination. The cases with a tumour and those with an arteriovenous malformation were all treated with gelatin sponge embolizatioected cases embolization is recommended alone or in combination with surgery.


Effects of glucocorticoids on differentiation of zona glomerulosa of fetal adrenal cortex of rats.

The tissue differentiation of the zona glomerulosa of the fetal adrenal cortex of rats was studied by giving experimental treatments to the fetus in vivo. A low-glucocorticoid-condition was given to the fetus by bilateral adrenalectomy of pregnant rats for removing exogenous glucocorticoids from the fetus, and by brain aspiration of the fetuses for removing the fetal pituitary gland (ACTH) and endogenous glucocorticoids. When the fetus was placed under a low-glucocorticoid-condition for the last couple of days of gestation, poor differentiation of the zona glomerulosa occurred specifically in the fetal adrenal cortex. The degree of the poor differentiation seemed to be proportional to the duration of the low-glucocorticoid-condition. Supplemental administration of glucocorticoids could prevent this poor differentiation of the zona glomerulosa. These results indicate that the tissue differentiation of the zona glomerulosa of the fetal adrenal cortex depends much on glucocorticoids.


Ultrastructure of mesodermal mixed tumor of the uterus.

A case of mesodermal mixed tumor arising in the uterus of a 57-year-old woman is presented. The tumor was a mixture of adenocarcinoma with occasional squamous metaplasia, stromal sarcoma, myxosarcoma and chondrosarcoma. Light and electron microscopic examinations of the tumor revealed close transition between stromal sarcomatous component and each of other sarcomatous and carcinomatous component. The histogenesis of mixed mesodermal tumor was discussed and it was concluded that the tumor might be derived from endometrial stromal cell which possessed the pluripotency to differentiate toward various epithelial and mesenchymal tissues including the heterologous mesenchymal tissue.


ELISA for herpes simplex virus (HSV) type-specific antibodies in human sera using HSV type 1 and type 2 polyspecific antigens blocked with type-heterologous rabbit antibodies.

Crude antigenic preparations made from rabbit cornea cells infected with either HSV type 1 or type 2 could be used in ELISA for titration of HSV type-specific antibodies in human sera. After immunochemical binding of the crude HSV antigens in microtitre wells by use of type-homologous rabbit antibodies, type-common antigenic sties were blocked with type-heterologous rabbit antibodies. Titration of human sera in this system showed that high concentrations of type heterologous rabbit antibodies were capable of completely blocking type-common antigenic sites, while leaving type-specific antigenic sites unblocked and capable of reacting with human antibodies. Thus HSV type-specific antibodies in human sera could be measured in ELISA without the use of purified typespecific antigens.


Influence of diethyldithiocarbamate (DDC) on the memory-facilitating effect of some central stimulants.

Diethyldithiocarbamate (DDC) introduced in a dose of 400 mg/kg 3 hours before training slightly deteriorates learning in albino rats in a maze. Upon testing 24 hours and 14 days after training, DDC is found to impair markedly the retention indices, when introduced both before and immediately after the end of the training. On the background of DDC, the stimulants caffeine, strychnine, amphetamine, echinopsine and centredrine do not manifest their typical memory-facilitating effect. According to data from the literature and from our previous experiments it is known that the DDC dose used lowers the noradrenaline level in the brain by more than 50 per cent. This suggests that the realization of the memory-facilitating effect of these central stimulants with different basic mechanisms of action requires optimum functional activity of the noradrenergic brain system, as well as this has been established in other experiments for the cholinergic system.


A case of alcoholic liver injury with an unusual polyacrylamide-gel disc-electrophoretic pattern of serum lipoproteins.

An unusual lipoprotein pattern on polyacrylamide-gel disc-electrophoresis was observed in 37 year-old male diagnosed as alcoholic liver injury. The electrophoretic lipoprotein pattern consisted of a major band of pre-beta mobility and minor intermediate, fast-beta and slow-alpha bands. The normal beta band was virtually absent and the alpha band was diminished. The abnormal lipoprotein pattern was observed one week after discontinuing alcohol consumption when marked hypertriglyceridemia demonstrated earlier had already normalized leaving a moderate hypercholesterolemia with reduced esterified cholesterol and abnormal liver function tests. The lipoprotein abnormalities were completely normal one month later. The appearance of a major pre-beta band with normal triglyceride and high cholesterol levels is discussed in relation to the formation of larger triglyceride-rich LDL particles in recovery from alcoholic hepatitis.


Lipoprotein abnormalities in cholestasis. I. Electrophoretic and ultracentrifugal analyses.

The alterations of lipid composition in sera of patients with liver diseases, particularly intrahepatic cholestasis and biliary obstruction, were studied by ultracentrifugation and polyacrylamide-gel disc-electrophoresis of lipoproteins and apoproteins. The elevation of serum cholesterol in intrahepatic cholestasis was greater than in biliary obstruction. The appearance of lipoprotein X in obstructive disease accounted for most of the increased cholesterol. The level of non-lipoprotein X cholesterol in intrahepatic cholestasis was significantly elevated, this being in part ascribed to the appearance of a new class of cholestatic lipoprotein, Slow-migrating HDL. The electrophoretic pattern of lipoprotein in cholestasis was generally characterized by a decrease in alpha band intensity and, in some types of cholestasis, by the appearance of Slow-migrating HDL. In addition, other abnormal lipoproteins exhibiting the characteristics of triglyceride-rich LDL (LP-Y), LP-X-like HDL and LDL-like HDL were found in some cases of intrahepatic cholestasis and biliary obstruction.


The mechanism of the release of hepatic enzymes in various liver diseases. 1. Alterations in cytoplasmic and mitochondrial enzyme activities in serum.

Serum glutamic oxaloacetic transaminase (GOT), mitochondrial GOT (GOTm), glutamic-pyruvic transaminase (GPT) and glutamate dehydrogenase activities were determined in 43 healthy controls and in 280 cases of liver diseases. A simplified column chromatographic method coupled with UV assay was employed for separation of GOTm. The activity was measured by following decrease in abosrbance of NADH at 340 nm. The lowest activity of GOTm determined with a coefficient of variation below 10% was 6 mIU/ml. High GOTm activities were found in acute hepatitis (acute stage), subacute hepatitis and primary biliary cirrhosis and were generally associated with high total GOT (GOTt) activities. The activity ratio of GOTm/GOTt varied depending on the stage and severity of liver diseases. The GOTm/GOTt ratio was decreased in acute, fulminant and subacute hepatitides. No significant reduction in the ratio was found in bile duct obstruction, alcoholic liver injury or metastatic liver cancer. Although relatively high GOTm/GOTt ratios were found in some patients with severe hepatic injury, they had no definite association with poor prognosis. These results indicate that the marked elevation in GOTt over GPT in advanced chronic hepatitis, liver cirrhosis and primary hepatoma was mainly due to preferential leakage of cytoplasmic GOT (GOTs).


Effect of nicomol on HDL cholesterol level.

In cardiovascular diseases with potential atherosclerosis, the serum concentration of HDL cholesterol as determined by a precipitation method with dextran sulfate and Mg++ was lower while that of total cholesterol was normal or elevated. Treatment with a daily dose of 1,200 mg of Nicomol, a derivative of nicotinic acid, for 1 to 3 months increased the mean HDL cholesterol level by 3 to 5 mg/dl and reduced the total cholesterol level by 14 to 15 mg/dl and total/HDL cholesterol ratio by 0.8 (3 months) to 0.9 (1 month, p less than 0.05). Similar decreases in HDL cholesterol concentration were also found in parenchymal and obstructive liver diseases with normal total cholesterol values except in fulminant hepatitis and intrahepatic cholestasis.


Small cell carcinoma of the lung: relation of calcitonin to bone marrow metastases, parathormone and gastrin.

The relations of calcitonin concentrations to the presence of bone marrow metastases and to the concentrations of calcium, parathormone and gastrin in serum were investigated in 74 untreated patients with small cell carcinoma of the lung. Calcitonin concentrations were enhanced in two thirds of the patients, while serum calcium concentrations were normal in all. In 19 of 57 patients parathormone concentrations were slightly above the normal range, but the concentrations of parathormone and calcitonin were not correlated. Bone marrow metastases had no influence on the concentration of serum calcitonin. Finally, a small inverse correlation between the concentrations of gastrin and calcitonin in serum was observed. The results resemble those of the calcitonin-producing medullary carcinoma of the thyroid, supporting the suggestion of an ectopic source of hypercalcitoninemia in small cell carcinoma of the lung.


Streptozotocin treatment of a pancreatic tumour producing VIP and gastrin associated with Verner-Morrison syndrome.

A 57-year-old male patient with metastasizing non-beta islet cell carcinoma of the pancreas is described. Both gastrin and VIP levels were elevated and the patient suffered from a syndrome of pancreatic cholera and hyperacidity. The tumour contained gastrin and VIP as demonstrated by immunofluorescence. The patient also had a history of familial renal stone formation and parathyroid nodular hyperplasia. Resection of pancreatic tumour in 1973 resulted in four years without symptoms. In 1977 definite signs of multiple hepatic metastases appeared. These signs disappeared after streptozotocin given in a dosage of 2 g three times at weekly intervals. The patient had remained well for 20 months after this treatment. The causative agents for the clinical syndrome in this case are discussed in view of circulating hormone levels.


Viral vaccines under development: a third generation.

In summary then, my purpose has been two-fold: on the one hand, I have tried to highlight the kinds of basic science advances in both cellular and virologic research that can (and should) be focussed both on vaccines under development and, retrospectively, on those whose origins were strictly empiric. On the other hand, I have attempted a partial survey of some of the prominent members of a potential new generation of vaccines to point out areas where these advances can and should contribute either to progress or to a sense of caution about the further reliance on pure empiricism. It is clear that we are not finished with new viral vaccines. It is equally clear that narrowing the persistent gap between basic science and its application to public health needs will require much energy and attention as vaccine development progresses.


The role of phosphoenolpyruvate and lactate production in insulin secretion.

There is a positive correlation between lactate output and insulin secretion but there is no correlation between total islet PEP content and insulin secretion and no correlation between cAMP production and insulin release. Neither PEP or cAMP seem to be primary triggers to insulin release but may rather act as positive modulators of insulin secretion. Potentially, PEP can maintain an elevated cytoplasmic Ca++ concentration by inhibiting Ca++ uptake in the mitochondria, increase the concentration of cAMP in the beta-cells by activating the adenylate cyclase (11) and change the phosphorylation state of the plasma membrane (12). The possible trigger effect of an increased glycolytic flux on insulin secretion may be mediated perhaps via changes in the NADH/NAD+ ratio (13). As regards the mechanism of potentiation of insulin release: in the fed state potentiation may be related to an increased glycolytic flux whereas this is not the case during starvation. Here enhancement of cAMP may play a role.


Method for measurement of human urinary kininase activity.

A method was developed to measure kininase activity in human urine. The method consists of dialysis of human centrifuged urine sample against phosphate buffer and partial fractionation of A-50 Sephadex column. The enzymatic property of urinary kininase, which destroys bradykinin when incubated, is estimated from its effect on a definite amount of bradykinin, using rat uterus.


Components of the kallikrein-kinin system in urine.

The excretion of kallikrein in urine varies, but the pathophysiologic implications are not clear. To help clarify the role of the urinary kallikrein-kinin system, we have begun to define components of the system as they occur in urine. To minimize artifacts which may arise through extensive purification procedures, we studied urinary protein concentrates prepared by ultrafiltration. The concentrates were separated by chromatography on Sephacryl. Urine contains abundant kininase activity, but in strongly inhibited forms. Kininase II is separable into at least two forms. Another major kininase can hydrolyze benzoyl-Pro-Phe-Arg and is inhibited by arginine but not by BPP9a or SQ 14,225. Its molecular weight is approximately 63,000. A third kininase, not inhibited by BPP9a, is excluded from Sephacryl. Human urine appears to contain only one kallikrein-like enzyme (MW 45,000). In addition, urine contains a protein (MW approximately 80,000) which reacts with trypsin to release bradykinin and which inhibits the hydrolysis of Pro-Phe-Arg-[3H]anilide by urinary kallikrein. Thus, in addition to kallikrein and kinins, urine contains kininogen and at least three kininase enzymes. Urinary ultrafiltrate contains an inhibitory substance (approximately MW 400).


Effect of bradykinin to cyclic AMP levels and response of murine lymphocytes.

No information is available on the pharmacological effect of bradykinin to lymphocytes and immunological responses of them. In this study it was clarified that bradykinin as well as histamine elevated cyclic adenosine 3',5' monophosphate (cAMP) levels of murine splenic or lymph node lymphocytes and mature thymocytes (cortisone-resistant thymus), but did not increase cAMP levels of immature thymocytes as well as histamine. The increased cAMP ratios in T cell-enriched splenic lymphocytes by the impulse of bradykinin were higher than that in splenic and lymph node lymphoid cells by the stimulation of bradykinin. It was also demonstrated that bradykinin as well as histamine suppressed DNA synthesis by mitogenic (PHA-P, Con-A) stimulation of splenic lymphocytes, but not a effect to the response of lymphocytes by mitogenic (LPS) stimulation was observed. These facts suggest that bradykinin may play an important role in the regulation of immunologic lymphocyte responses.


Pulmonary anaphylaxis and the kallikrein-kinin system.

The kallikrein-kinin system has been thought to participate in the pathogenesis of anaphylaxis. Kallikrein, released from lungs, has been postulated to contribute to cardiovascular collapse. Further to test the hypothesis, we examined for the occurrence of a kallikrein-like enzyme in guinea pig lungs and examined for release of such an enzyme by isolated, perfused lungs of guinea pig sensitized to and challenged with egg albumin. In addition, we treated guinea pigs with the bradykinin potentiating agents, BPP9a and SQ 14,225. In parallel experiments, we examined for effects of non-steroidal anti-inflammatory agents on the supposition that prostaglandin-related substances may mediate or modulate actions of kinins during anaphylaxis. A plasma kallikrein-like enzyme was found in lung homogenates and occurred in concentrations greater than that of plasma itself. Similarly, a store of kininogen occurs in lungs. However, using a sensitive radioassay for kallikrein-like enzymes, we were unable to confirm that antigenic challenge of sensitized lungs causes the release of enzyme into pulmonary venous effluent. Further, we were unable to modify the acute course of anaphylaxis by pretreatment of guinea pigs with bradykinin potentiating agents. However, indomethacin and aspirin at 20-40 mg/kg were found to greatly increase the severity of pulmonary anaphylaxis in terms of increased resistance to ventilation and increased numbers of lung hemorrhages. Paradoxically, aspirin or sodium salicylate at 80-100 mg/kg prevents the characteristic rise of insufflation pressure and the formation of lung hemorrhages.


Altered urinary excretion of human kininase activity in acute myocardial infarction.

This study concerns the determination of levels of human urinary kininase excretion in acute myocardial infarction (AMI). The results obtained by a biological method show that there is a significant reduction of the enzymatic activity in patients affected by AMI in comparison with normals (6.4 +/- 0.4 ng of destroyed bradykinin/min. versus 164.4 +/- 31.4 ng; P less than 0.001), while urinary kallikrein excretion was close to normal values.


The role of the kidney in vitamin D metabolism.

The kidney should be regarded as an organ of central importance in the regulation of calcium metabolism. Its secretion product, 1 alpha,25(OH)2D3, is regulated by several factors, including the calcium and phosphorus content of the diet, parathyroid hormone and the level of 1 alpha,25(OH)2D3 itself. The main occasions in health where 1 alpha,25(OH)2D3 secretion is enhanced are during growth and reproduction. In these situations the secretion of this new renal hormone is under at least partial control of growth hormone and prolactin.


Metabolic and cellular activity of vitamin D.

Most of the effects of vitamin D on calcium and phosphorus homeostasis result from an increase in intestinal absorption of calcium and phosphorus and from bone mobilization. These effects are due to 1,25(OH)2D3, one of the renal vitamin D metabolites. Besides ionic mobilization, vitamin D may exert additional effects on bone which depend on metabolites other than 1,25(OH)2D3. Kidneys, parathyroid glands and muscle are probably target organs for vitamin D. The metabolite(s) responsible for these actions remain unknown.


Pathways of arachidonic acid metabolism and modulation by drugs.

The AA cascade in addition to producing various oxygenation products concomitantly yields an oxygen radical. This oxidant selectively deactivates the cyclooxygenase, peroxidase and PGI2 synthetase components whereas TXA2 synthetase is resistant to this oxidant. On the basis of available data it is not possible to assign an inflammatory inducing role to this oxidant on the basis of these actions. Other loci of action must be involved. Among the possibilities are the elements involved in the release of arachidonic acid. Studies relating to this possibility are examined in this report.


[Action of vitamin D and E on the erythrocyte membrane. II. Morphological changes in the erythrocytes studied by transmission electron microscopy].

Man, rabbit, guinea-pig erythrocytes treated "in vitro" with high doses of cholecalcipherol or alpha-tocopherol release K+ and haemoglobin and show ultrastructural damages. These damages consist in a change of the red cells profile as well as in the desappearance of the glycocalix, in alterations of the membrane and of the cortical cytoplasm structure. These ultrastructural alterations are of a different degree, depending on the animal species; they partly resemble the erythrocyte changes induced by retinol. Our results are in partial agreement with the Dingle and Lucy's hypothesis on the common action of liposoluble vitamines on the erythrocyte membrane.


Application of case series review results to the evaluation of individual cases in diagnostic radiology.

Probability theory provides a simple method for physicians to use their "intellectual linkages" to their past clinical experience in making current diagnoses. Only a pencil and paper are required for making a few likelihood calculations. To illustrate this method, evaluation was done of a new diagnostic sign (presence of knee ossification centers) for differentiating rubella from cytomegalovirus infection in young infants. Two practical questions can be answered by use of this method for calculating probabilities: (1) How certain can one be about either diagnosis when centers are present or absent? (2) How can other radiologists apply these results to their individual cases?


Relationship between extent of coronary artery disease and correlative risk factors.

An analysis was made of correlative factors which might be related to the angiographically measured extent of coronary artery disease in 140 patients. All patients presented with clinically important chest pain. Thirty-three had a normal coronary arteriogram. The extent of the atheromatous process was measured precisely at angiography by three different techniques. A coronary score, based on the percentage of luminal narrowing, was found to be best suited for the analysis. The most important contributory factors to the severity of atherosclerosis was duration of clinical history, number of previous myocardial infarctions, and male sex, but more specifically elevation of serum cholesterol and diabetes mellitus. Cigarette smoking, obesity, hypertension, a family history of atherosclerosis, and elevated serum triglycerides had a positive influence but this was not statistically significant.


Role of calcium and cyclic adenosine 3':5' monophosphate in regulating smooth muscle contraction. Mechanisms of excitation-contraction coupling in smooth muscle.

Caclium initiates smooth muscle contraction by activating an enzyme, myosin light chain kinase. This enzyme catalyzes the transfer of phosphate from adenosine triphosphate to the 20,000 dalton light chain of myosin. In its phosphorylated form myosin interacts with actin to produce muscle contraction. The mechanism by which calcium activates myosin kinase requires (1) the binding of calcium to a 16,500 dalton calcium-binding protein (calmodulin), and (2) the binding of calmodulin-calcium to a 125,000 dalton catalytic subunit. This two protein complex is the active form of myosin light chain kinase. Smooth muscle relaxation is mediated by cyclic adenosine 3':5' monophosphate (cyclic AMP). One nechanism by which the latter may exert a direct effect on actin-myosin interaction is through the activation of a cyclic AMP-dependent protein kinase that can phosphorylate the 125,000 dalton component of myosin light chain kinase. Phosphorylation of myosin light chain kinase decreases the activity of the enzyme, thus favoring the unphosphorylated form of myosin, which cannot interact with actin to produce smooth muscle contraction.