Attempts to produce Theileria parva-infected mouse cells using cell fusion techniques. Ehrlich ascites tumour (EAT) cells were fused with Theileria parva-infected bovine lymphoid (C2) cells using inactivated Sendai virus. A variety of techniques were employed to try and increase fusion percentage and harvest of heterokaryons. There was no evidence that pre-exposure of C2 cells to Sendai virus or phytohaemagglutinin improved fusion percentage, but the percentage was higher when 10(8) C2 cells were fused with 10(7) EAT cells, as compared with a ratio of 10(7) C2: 10(6) EAT. An increased yield of multinucleate cells was obtained using a calf serum gradient to separate cells of different sizes. An attempt to fuse EAT cells with free macroschizonts was not sucessful. When cells were grown in hypoxanthine/aminopterin/thymidine medium (HAT), T parva appeared to be selectively killed by the aminopterin present; this finding would seem to militate against the use of a HAT selection system to clone parasitised hybrids. C2 cells could be selected out by passage of mixed cultures through mice, but no evidence of parasitosis was detected in EAT cells which became established.


Pulmonary reflexes and breathing pattern during sleep in the opossum. Paradoxical sleep (PS) in the opossum (Didelphis virginiana) and other mammals is typically accompanied by irregular breathing, while even breathing is usually found during slow wave sleep (SWS). During PS certain brainstem reflexes are depressed, and it is possible that similar depression of pulmonary reflexes could contribute to the observed ventilatory uneveness. To test this possibility, we assessed pulmonary reflexes in the opossum during SWS and during PS when breathing was irregular. Prolongation of expiratory duration with airway occlusion at end inspiration and prolongation of inspiratory duration with airway occlusion at end expiration are both associated with pulmonary reflexes activated by lung inflation. These responses were obtained during PS, and the results suggested that the reflex effects, could be as prominent during PS as during SWS. Pulmonary deflation, producted by raising pressure around the thorax, increased breathing rate during both PS and SWS and generally increased the regularity of respiration during PS. Results of this study do not support the idea that irregular breathing during PS is associated wtih maintained depression of pulmonary reflexes.


[Hansen's neuritis in the form of pseudysyringomyelia. Clinical, diagnostic and therapeutic consideration a propos of 3 cases]. Three cases of neuropathic leprosy (one Moroccan, two non-colonial immigrants) enable attention to be drawn to two aspects of theproblem of Hansen's neuritis: 1) such cases should no longer be considered exceptional, infection occuring in countries where leprosy is endemic but the disease developing years later in any country; 2) among the various neurological aspects of neuritis due to Hansen's bacillus, great stress is laid on sensory disorders of the syringomyelic type, with thermalgesic dissociation; although these symptoms have been considered typical (our three cases are an illustration of this), they seem to occur fairly rarely and are the cause of difficulties in diagnosis as it is the last thing one would think of. Treatment of these neural forms is not encouraging, in spite of a therapeutic arsenal which in theory is considered effective.


[Mixed neuropathies in rheumatoid arthritis. Motor and sensory nerve conduction velocities]. Nerve conduction studies and analysis of the sensory action potential (110 nerves investigated) demons treated abnormalities in 15 to 20 patients with rheumatoid arthritis. It is concluded that moderate, often subclinical peripheral neuropathy is a common complication in rheumatoid arthritis.


[Sleep disorders in Steele-Richardson disease. Polygraphic study of 3 cases]. 24 recordings of night-time sleep in three patients suffering from progressive supranuclear paralysis were carried out. There was observed: a tendency to insomnia, disappearance of spindles, an invasion of slow sleep immediately it appeared by the muscular and ocular criteria of paradoxical sleep, a considerable reduction in paradoxical sleep in the strict sense of the term, the latency of which in making its appearance was, however, maintained; progressive invasion of the paradoxical phases by slow waves. These abnormalities differ from those found in Parkinson's disease.


[Volitional postural dyskinesia with hypertrophic neuropathy]. Two cases of voluntary postural dyskinesia with hypertrophic neuropathy are reported. Electron-microscope studies revealed in one case a hypertrophic neuropathy with onion bulb formation, in the other axonal degeneration. The findings are compared with those of Pierre Marie-Boveri disease, of Roussy-Lévy disease and with the case of Salisachs and Lapresle (1973).


[Neurological manifestations in monoclonal gammapathies. Pure neurological manifestations. Immunofluorescence study]. Analysis of 105 peripheral and central nervous system complications in 1062 monoclonal gammapathies draws attention to two types of phenomena. The possibility of pure neurological manifestations of IgM monoclonal gammapathies with macroglobulinorachia leads to discussion of their nosological position in relation to Waldenström's disease, Burkitt's lymphoma and Marek's disease. It is suggested that these cases should be reclassified under the heading "secreting neurolymphomatosis". Immunofluorescence and electron microscopy of 10 biopsies of the peripheral nerve showed deposits of monoclonal immunoglobulin whose function in determining peripheral neuropathies is discussed. The simultaneous presence of lymphoid infiltration, amyloid deposits and the monoclonal immunoglobulin (M component) suggests that this immunoglobulin could be the link between the cellular infiltrate secreting it and amyloid infiltration which would be the visible manifestation of it.


[Clinical syndrome of convulsive cough of adenoviral etiology in a children's collective]. Bacteriological, viral and serological investigators were carried out in a community with 100 prescholar children (Kindergarden), 34 of whom presented a clinical syndrome of whooping cough, in order to establish the bacteriologic or viral etiology of the syndrome. The etiologic role of organisms of the Bordetella, B. pertussis and B. parapertussis was invalidated by the bacteriologic and serological tests. Viral and serological tests, performed to demonstrate the participation of viral agents in the causation of this clinical syndrome, established an adenoviral diagnosis in 13 (43.3%) of the 30 children. Adenovirus type 6 was isolated and there was a significant increase in the titers of antibodies to adenoviruses.


Ultrastructural aspects of crystal-like inclusions in a case of IgA plasma cell proliferation. A case of apparently benign plasma cell proliferation is described. Needle-like paracrystalline inclusions were observed in numerous plasma cells outside the cisternae of the rough endoplasmic reticulum. They had a dense protein core surrounded by a layer of carbohydrate. They were found only in plasma cells secreting IgA-kappa immunoglobulin, but did not react with labelled specific antisera. A small amount of paraprotein IgA-kappa was found in the serum but no Bence-Jones protein could be detected in the urine. These observations suggest that these plasma cells synthesize normal IgA immunoglobulin and accumulate abnormal protein in the form of paracrystalline inclusions.


[Some respiratory viruses in the etiology of acute upper respiratory infections]. The viral etiology of acute respiratory diseases, determined in 107 children admitted to hospital during the 1966-1969 period, was confirmed in 36% of the cases by isolation of the viral agent and in 59% by serologic reactions. Parainfluenza viruses, especially of type 1 and 3, were encountered more often in the etiology of acute or obstructive laryngitis, and the syncytial respiratory virus in tracheobronchitis.


Thrombin-induced platelet prostaglandin and cyclic AMP production and a possible intrinsic modulation of platelet function. In previous studies, we observed an increase in intracellular cyclic AMP in platelets during thrombin-induced nucleotide and calcium release. Our present work suggests that platelet prostaglandins are directly involved in this phenomenon. Washed human platelets were incubated at 37 degrees C with human thrombin for times ranging between 5 s and 5 min. The release of nucleotides and calcium in response to thrombin, determined spectrophotometrically, reached 40-60% of maximal plateau levels by 5 s, 70-80% by 10 s, and 90-100% by 15 s. The production and secretion of prostaglandin E (PGE), measured by radioimmunoassay, parelleled this rapid time course. After 10 s, however, the amount of extracellular PGE began to decrease, continuing to do so through 5 min of incubation. Intracellular cyclic AMP accumulation, determined by radioimmunoassay, lagged behind the time course of nucleotide and calcium release, and that of PGE secretion, by several seconds. This lag in cyclic AMP accumulation appeared to correlate closely with the disappearance of PGE from the supernate in the same platelet samples. In view of the inhibitory effects of cyclic AMP and PGE on platelet release and aggregation, these interrelated time course curves suggest the existence within platelets of a mechanism for the modulation of platelet activity.


Precision and accuracy of foundry dust exposure estimates from air sampling data. Errors in the sampling methods and in the determination of respirable size quartz in foundry dust have been evaluated and discussed. In general, the total precision of dust sampling and analysis was better than 20%. The term "exposure dose" is introduced and defined. The temporal variation associated with measuring exposure dose is assessed with reference to the use of a log-normal distribution of air sampling results. The logarithmic standard deviations of dust concentrations at fixed sites and jobs are calculated.


Dust exposure in Finnish foundries.

Dust exposure in Finnish foundries. Dust measurements were made in 51 iron, 9 steel, and 8 nonferrous foundries, at which 4,316 foundrymen were working. The sampling lasted at least two entire shifts or work days continuously during various operations in each foundry. The dust samples were collected at fixed sites or in the breathing zones of the workers. The mass concentration was determined by weighing and the respirable dust fraction was separated by liquid sedimentation. The free silica content was determined by X-ray diffraction. In the study a total of 3,188 samples were collected in the foundries and 6,505 determinations were made in the laboratory. The results indicated a definite difference in the dust exposure during various operations. The highest dust exposures were found during furnace, cupola, and pouring ladle repair. During cleaning work, sand mixing, and shake-out operations excessive silica dust concentrations were also measured. The lowest dust concentrations were measured during melting and pouring operations. Moderate dust concentrations were measured during coremaking and molding operations. The results obtained during the same operations of iron and steel foundries were similar. The distribution of the workers into various exposure categories, the content of respirable dust and quartz, the correlation between respirable dust and total dust, and the correlation between respirable silica and total dust concentrations are discussed. Observations concerning dust suppression and control methods are briefly considered.


The Finnish foundry project. Background and general methodology. The general methodology of the Finnish foundry project is presented. The project comprised dust measurements from all Finnish iron and steel foundries and a sample of nonferrous foundries, measurements of chemicals used in most foundries, and a mortality, morbidity and turnover study of active and retired foundry workers. The total budget of the project was Fmk 1,155,000 (+ 305,000). It was started in April 1972 and completed in May 1975. The project had the practical objective of developing recommendations for improvements in work conditions in individual foundries. More specific details of the methodology are reported in other communications.


Phosphatases in lake water: characterization of enzymes from phytoplankton and zooplankton by gel filtration. Sephadex gel filtration was used to characterize phosphomonoesterases in two small takes in northern Sweden. Two fractions, here termed phosphatase A and phosphatase B, were found both as free enzymes and associated with seston. The activity of phosphatase A was correlated with the presence of algal biomass. Phosphatase B, on the other hand, was derived from zooplankton. Phosphate served as an effective inhibitor of phosphatase A but had no such effect on phosphatase B. Both fractions had pH optima between 6.5 and 7.0.


[Phosphorus and calcium metabolism in the normal pregnant woman]. The authors consider various aspects of calcium metabolism in pregnant women and the reciprocal influences of endogenous variations in the levels of parathormone, calcitonin, vitamin D, oestrogens and the interferences between calcium metabolism in the mother and that in the foetus. They note the precautions which should be taken for the neonatal calcium balance to be stable.


[Chronic urticarial lesions and macroglobulinemia. Apropos of 5 cases]. The authors report 5 cases whose main characteristics appeared very similar. Constantly, they found the same skin signs, urticaria without pruritus, recurring over a long period. The latter was accompanied by a very high E.S.R. and immuno-electrophoresis showed, in all cases, an increase in monoclonal IgB, permitting one to make the diagnosis of macroglobulinemia. In four cases out of five, this clinical picture was accompanied by bony pain associated with radiological signs of condensation. The symptoms were accompanied by prolonged fever and lymphadenopathy. After being well tolerated for a long period, the disease may become worse and lead to death. Thus this seems to be a true disease entity?


[Paradoxical effect of forced inspiration: a new characteristic of asthmatic disease?]. In normal subjects, forced inspiration may dilate the bronchi and be considered as a defence or compensatory reaction in certain cases. In asthma, forced inspiration has the opposite effect. Bronchospasm occurs or becomes worse, usually moderately and transiently, but sometimes to a marked and lasting degree. These reactions may be prevented by anticholinergic and sympathomimetic drugs. They should be avoided and one should thus prohibit the manoeuvres which trigger them off. One should take them into consideration during respiratory function tests. This paradoxical effect of forced inspiration seems to exist to various degrees in most asthmatic patients, it may be considered as a diagnostic sign of asthma.


[Calcium metabolism after the menopause]. The authors recall the antagonism between estradiol and parathormone. Estradiol tends to lower serum calcium and fix calcium in the bones as shown by one of us 25 years ago. The mechanism of this action of estrogen on calcium metabolism has been determined by numerous authors but some points are still not clear, e.g. the interferences between estrogen and calcitonin. Classically, parathormone is known to increase bony reabsorption and raise serum calcium. After the menopause the gradual reduction in estradiol secretion leads to post-menopausal osteoporosis. It is better to administer estrogens prophylactically to women after the menopause provided a cervical smear and mammography have been carried out to eliminate latent carcinoma of the breast or uterine cervix.


[Cerebral metastases and their revealing forms in a series of 156 cases. Contribution of cerebral scintigraphy to the diagnosis and indications for surgery]. This series of 156 cases of brain metastases collected over a period of 14 years may be divided up into 65 considered as multiple following further investigation and thus refused for surgery, and 91 considered as simple and operated on. Our conclusions are very similar to those presented recently to the French Society of Neurosurgery. Emphasis is however placed on the frequency of metastases which are the first sign of cancer and thus resemble a cerebral tumour. Postoperatively the primary tumour continues to develop for it is often not found. Even under these conditions, a single metastasis should lead to operation and it may be distinguished from multiple metastases by a brain scan together with angiography which often permit not only the diagnosis of malignant tumour but also its secondary nature. The scan was positive in 85% of our 78 cases including 20 gamma-encephalographies and 58 angioscans. The diagnosis of metastases was possible in only 57% where as other authors have accorded more specificity to this investigation.


[Effects of asbestos on respiratory pathology. 27 cases observed in 6 years in a pneumo-phthisiology department in Nantes]. A search for respiratory disease due to asbestos permitted the authors, during a review of 6 years' activity on a Chest Unit in Nantes, to collect 27 cases which represents 2.4% of all cases examined. They were male subjects usually aged about 60 years exposed to dust mildly but continuously during a long career as metal workers, mainly in the shipyards. Pleural involvement was constant, usually limited to characteristic pleural calcifications which were well tolerated. Two cases of asbestos pleurisy were diagnosed, but above all we noted 7 cases of mesothelioma with a very poor prognosis. It is difficult to say whether asbestos is responsible for bronchial carcinoma but we noted two cases in patients with calcifications. The authors emphasise the necessity for revision of the table of occupational diseases which does not yet include pleural disease due to asbestos.


[Clinical and statistical study of 100 vitiligo patients. I. Etiologic factors and clinical study]. A study of the etiological factors in 100 cases of vitiligo showed female predominance (59%) variable age of onset, absence of radial factor, moderate influence of psychological, physical or endocrine factors, the large number of subjects belonging to group B, a family history in 18% of cases. The morphology site and course of the lesions were also studied. There was no significant correlation between the course of the disease and the various etiological and clinical parameters studied.


[Streptozotocin and malignant insulinomas. Apropos of the case. Review of the literature]. In spite of possible toxicity streptozotocin now appears to be the best treatment for malignant islet cell tumour with liver metastases, i.e. inoperable tumours with a poor prognosis either due to extension of the tumour itself or due to hypoglycemic attacks. Out of about 60 patients thus treated, 1 to 2 years survival were obtained. 22 out of 52 patients reported by Broder and Carter are still alive and one may estimate the overall percentage of favourable results at 65%. On the other hand out of another 100 patients treated elsewhere with this antineoplastic agent, only a few cases of carcinoid tumour gave encouraging results. The course of the others was not modified significantly.


Adaptation of cells derived from human malignant tumours to growth in vitro. Forty-five human malignant tumour specimens were cultivated in vitro in an attempt to determine the necessary conditions for tumour cell maintenance and to establish permanently-growing cell lines. Continuously-growing cultures were derived from five tumours, including carcinomas of the oesophagus and colon, a hepatoma, a mesothelioma and a retroperitoneal sarcoma. The carcinoma of the oesophagus and the hepatoma, which have adapted fully to in vitro conditions, can be regarded as established cell lines.


Occurrence of primary hepatocellular cancer and peliosis hepatis after treatment with androgenic steroids. Three patients are reported in whom treatment of Fanconi's anaemia with androgenic steroids was complicated by the development of either primary hepatocellular cancer (PHC) or peliosis hepatis. The first, a White woman aged 34 years, was found to have PHC after receiving first methyltestosterone and then oxymetholone for a total period of 7 years. She died 4 months after the diagnosis was made. The other 2 patients were White children who presented with peliosis hepatis after receiving methyltestosterone and oxymetholone for 8 years and oxymetholone for 5 years, respectively. Both died from their primary diseases shortly after oxymetholone treatment was discontinued. Possible pathogenic mechanisms involved in the development of these serious complications are discussed and the therapeutic dilemma raised by their occurrence is emphasised.


The chest radiograph in primary liver cancer: an analysis of 449 cases. The value of plain chest radiography in the diagnosis of primary hepatocellular cancer (PHC) was assessed in 449 patients. An elevated right hemidiaphragm and pulmonary metastases were present in 11% and strongly suggest a diagnosis of PHC. In all, the right hemidiaphragm was raised in 30% of patients. Pulmonary metastases were present on admission in 19% of patients and appeared later in a further 6%. Secondary deposits were found in the lungs at necropsy in 52% of patients, compared with only 24% in whom there was radiological evidence of metastases during life. In 36% of patients chest radiographs were normal on admission.


Treatment of cerebral vasospasm by control of cyclic adenosine monophosphate. Twelve patients with cerebral vasospasm following subarachnoid hemorrhage were treated with intravenous aminophylline and isoproterenol. After angiographic demonstration of spasm, all patients were begun on a continuous intravenous infusion of isoproterenol, 125 mug/hr, and aminophylline, 125 mg/hr, for a period of up to two weeks. The infusion was continued until there was clinical or angiographic evidence that spasm had diminished. Nine patients improved on this regimen and three remained unchanged. The use of isoproterenol and aminophylline is based on their effect on the enzymes responsible for the formation and degradation of cyclic adenosine monophosphate (cyclic AMP). An increase in cyclic AMP has been noted to produce relaxation of vascular smooth muscle. It is proposed that manipulation of these biochemical pathways may provide a method for influencing blood flow through cerebral vessels.


The surgical implications of estrophile protein estimations in carcinoma of the breast. Assays of estrophile protein (ER) in 161 patients with no previous additive or ablative hormonal therapy have been analyzed; 47.2 percent were ER positive; 52.8 percent ER negative. A total of 37.5 percent of premenopausal and 50.8 percent of postmenopausal patients had ER-positive tumors. The effects of additive and ablaive hormonal therapy were observed in 75 patients; 63.5 percent of the ER-positive group and 8.6 percent of the ER-negative group responded, but the incidence in the ER-negative group is thought to be spuriously high. The level of the ER content in the ER-positive group did not influence the degree of response. The ER-negative group had a shorter life span after discovery of the tumor and was more likely to develop dominant visceral metastases. Of 15 patients followed with sequential ER assays after hormonal therapy (additive and/or ablative), 14 demonstrated substantial falls in ER levels but these did not correlate with the clinical response. Tumor assayed in nine patients after irradiation of the lesion contained no demonstrable ER. ER assays of breast cancer tissue proved to be a useful but imperfect tool in predicting clinical progress following hormonal maneuvers but some readings may be spuriously low due to imperfect techniques of measurement, prior exogenous hormonal administration or hormonal ablation, and previous irradiation of the tumor.


Precise selection of breast cancer patients with bone metastasis for endocrine ablation. To enhance the precision of selection of breast cancer patients with bone metastasis for endocrine ablation, 85 patients underwent a Levodopa test for 4 consecutives days. Assessment of the result of the test was made on the basis of thorough clinical evaluation, x-ray examination, and results of serum and skin tests as well as cancer receptor studies when tissue was available. Results of 23 surgical procedures were as follows: bilateral oophorectomy elicited good clinical response in five patients with positive preoperative Levodopa tests; one negative clinical response followed a negative Levodopa test; bilateral adrenaloophorectomy in nine patients elicited good response in seven who had positive Levodopa tests and negative responses in two patients who had negative Levodopa tests; bilateral adrenalectomy in eight patients elicited good response in five patients with positive Levodopa tests and negative responses in three who had negative Levodopa tests. There were no deaths and there was only one complication after operation. Levodopa testing appears to be an effective means for selection of patients with bone pain from recurrent breast cancer who will benefit from endocrine ablation. When the Levodopa test was negative for bone pain relief, endocrine ablation was of no benefit to the patient.


Fibrous histiocytoma of the lung.

Fibrous histiocytoma of the lung. A case of asymptomatic fibrous histiocytoma of the lung is described in a 14-year-old girl. A left thoracotomy was performed followed by partial resection of the lingula. Postoperative progress was uneventful.


Metabolic properties of human platelet membranes. II. Thrombin-induced phosphorylation of membrane lipids and demonstration of phosphorylating enzymes in the platelet membrane. Washed human platelets have been labeled with either 32Pi or glycerol-1-14C and the distribution of the label in the phospholipids determined. 32Pi was introduced primarily into polyphosphoinositides, i.e. di- and triphosphoinositide, whereas the label from glycerol which indicates de novo synthesis of lipid molecules did not appear in these phospholipids. In the course of thrombin-induced aggregation and release the phosphate incorporation into phosphatic acid, di- and triphosphoinositide was rapidly stimulated in parallel to the platelet reaction. The incorporation of glycerol did not change under the same conditions. It is concluded that phosphoinositides with rapid incorporation of phosphate groups are not as rapidly synthesized de novo and presumably form a separate phospholipid pool in the platelets. Only the phosphorylating reactions are stimulated by the thrombin aggregation. The necessary enzymes for these reactions, namely diglyceride kinase, phosphatidylinositol kinase, and phosphatidylinositol-phosphate kinase all can be shown to be associated with a well characterized platelet membrane fraction.


Modification of survival of gamma irradiated mice by adenosine nucleotides. The administratio prior to irradiation of adenosine triphosphate (ATP) or other adenosine nucleotides, singly or in combination, increased the radioresistance of mice. Post-irradiation treatment with the adenosine nucleotides had no effect on the survival of the irradiated mice. Dose reduction factors of 2.32 could be obtained by pretreatment of mice with the following combination of protective agents: S-2(4-aminobutylamino)ethyl phosphorothioic acid(WR 2822), cysteamine (MEA) and ATP. Since cyclic AMP levels were unchangd in the spleen or gut by administration of cysteamine and other protectors it is unlikely that the increase in preotection was due to changes in cyclic AMP levles. The calcium salt of ATP provided a higher level of protection than the ATP alone, indicating that the protective mechanism of ATP is probably not related to anoxia.


Progesterone secretion by adrenal glands of hamsters and comparison of ACTH influence in rats and hamsters. Studies were designed to determine a) if adrenal glands of hamsters secrete progesterone (PROG), b) the effects of adrenocritocotropin (ACTH) administration on adrenocortial function of rats and hamsters under the surgical conditions necessary for collection of adrenal venous blood from the left renal vein, and c) the effects of blood loss during sample collection. PROG was quantitated by the competitive protein-binding method after extraction and separation by sephadex LH-20 column chromatography. The presence of interfering quantities of androstenedione necessitated two column chromatographic steps. Glucocorticoids (11-OHCS) were determined fluorometrically. PROG was detected in adrenal venous plasma of female hamsters. The PROG concentration and secretory rate were 91 +/- 12 ng/ml and 4 +/- 1 ng/min, respectively, while the peripheral plasma level of the same animals was 2 +/- 0.2 ng/ml, indicating that the adrenal glands of female hamsters are capable of secreting PROG. ACTH administration increased PROG secretory rates in both hamsters (3 +/- 1 to 14 +/- 3 ng/min) and rats (62 +/- 9 to 152 +/- 32 ng/min) on estrus, as well as increasing the 11-OHCS secretory rate of hamsters (16 +/- 1 to 33 +/- 4 ng/min), but not of rats. The greater increase in PRCC than in 11-OHCS secretion may be related to excess PROG formation relative to the capacity of the 17alpha- or 21-hydroxylating enzyme systems. The adrenal venous PROG concentration and secretory rate of female hamsters infused with 10% dextran while collecting adrenal venous blood did not differ significantly from those of the non-infused animals, suggesting that this amount of blood loss (1 ml) does not influence PROG secretion.


Acute haemorrhagic conjunctivitis and enterovirus 70 in Kenya. The pandemic of acute haemorrhagic conjunctivitis that started in Ghana in 1969 and spread to many countries in Africa, Asia and Europe reached Kenya in April 1971. From one patient virus was isolated. This was possibly the first strain ever isolated of Enterovirus 70. Identification took time and was finished long after the publication of isolation of the new virus in Japan. Cross neutralization tests with the virus from Japan showed close relationship between the two. During a second epidemic in Kenya in 1974 many more strains of the virus were isolated. The history of isolation and identification and the clinical picture of the disease as seen in Kenya are described.


Studies with bluetongue virus in Nigeria. Using an agar gel diffusion test antibody evidence indicates that bluetongue virus is widely distributed in Nigeria and commonly infects cattle, sheep and goats. In a single dairy herd serological conversions were observed in both wet and dry seasons.


[Rare kidney tumours (author's transl)]. In 508 patients with tumours of the kidney, 14 rare neoplasms has been found. These are analyzed with regard to diagnosis, therapy, and prognosis.


Papillary adenocarcinoma of prostate.

Papillary adenocarcinoma of prostate. Papillary adenocarcinomas of the prostate are rare tumors which may arise from the prostatic ducts and the utricle; 2 cases are described. The diagnosis of these tumors is best established by cystourethroscopy and transurethral resection. The more common prostatic acinar adenocarcinoma is frequently associated with these tumors. The histopathologic recognition of papillary adenocarcinoma of the prostate and its differentiation from acinar adenocarcinoma is important since the natural history and response to treatment may be different.


Unusual presentation of Wilms' tumor.

Unusual presentation of Wilms' tumor. A Wilms' tumor, completely filling the collecting system of a kidney, led to nonfunction of the involved kidney. Histologic examination proved absence of renal vein involvement. Review of our case material and discussions with other centers showed that this unusual presentation has been seen elsewhere.


[Surgical treatment of patients with malignant non-epithelial tumors of the stomach]. Under study were the data obtained in 29 patients with malignant nonepithelial gastric tumors, which indicated a high incidence of this affection in persons under 50. Gastric reticulosarcomas are most frequently observed. The diagnosis is very difficult to establish both before and during laparatomy. Favourable late results were most frequently noted in patients subjected to radical surgical interventions. Radical and tentative laparotomies may be followed by chemo-or radiotherapy.


Spontaneous Pancreatic beta cell tumor in the rat. A light and electron microscopic study. Fine structural study of a pancreatic neoplasm found at autopsy of a 27-month-old female Long-Evans rat showed that the tumor consisted of, and derived from beta cells of the islets of Langerhans.


Giant cell tumor of soft parts. An ultrastructural study. The light-microscopic and ultrastructural findings in a case of so-called giant cell tumor of soft parts, localized at the dorsal side of the left foot of a 23-years-old male are described. An amputation of the lower extremity was performed and subsequently chemotherapy with adriamycin was given for 3 months. Despite the histology and cytologic malignant appearance and the evident vascular invasion, already present at the time of the first excision, the last known status 2 years later seems favorable. There are no pathologic lymph nodes in the groins and no signs of metastases on chest X-rays. From the electron-microscope study no definite conclusion can be drawn as regards the histogenesis of this tumor. we feel, as do others, that many of the principal mononuclear tumor cells are poorly differentiated mesenchymal cells. Some of the neoplastic cells, however, show ultrastructural features suggestive of chondro- or osteoblasts (a well-developed r.e.r. containing electron-dense material; multiple Golgi complexes; masses of glycogen; interdigitating cell membrane villi; cytoplasmic filaments; an extracellular amorphous matrix). Some of the larger tumor cells have the submicroscopic aspects of histiocytes as described in osseous, cutaneous, or pulmonary lesions of the histiocytosis X group. As yet undetermined cytoplasmic inclusion bodies constitute another rare observation in our material.


[Intracytoplasmic inclusions within cells of the breast and their diagnostic significance (author's transl)]. There were 700 tissue biopsies of the breast with and without carcinomas examined simultaneously by intraoperative histology and imprint cytology. In 20.2% of the cases with carcinoma the tumor cells showed peculiar intracytoplasmic inclusions, whereas in only 0.43% of the biopsies of the mamma without carcinoma such inclusions were to be found. Their morphologic variation and the histochemical pattern are discussed. It is pointed out that these intracytoplasmic inclusions may be a helpful histopathologic feature in the diagnosis of breast cancer.


Cellular differentiations and structural characteristics in nasopharyngeal angiofibromas. An electron-microscopic study. An electron-microscopic study of 9 nasopharyngeal angiofibromas was performed in order to elucidate the ultrastructural characteristics. Stromal fibroblasts and proliferating cells of the microvasculature were found. The stromal fibroblasts were subdivided into 3 different groups: (1) "classical" fibroblasts, (2) fibroblasts with histiocytelike features, and (3) fibroblasts with myoid features. By proliferation the cells of the capillary vessels change into stromal cells. A particular pattern of nuclei and dense intranuclear granules is only found in stromal fibroblasts. Consequently fibroblasts as well as cells of the microvasculature contribute to the pool of tumor cells.


Cellular origin of human pancreatic polypeptide (HPP) in endocrine tumours of the pancreas. Pancreatic polypeptide (HPP) producing cells were detected in 23 out of 36 endocrine tumours of the pancreas. In all tumours shown to be producing two hormones it was possible to demonstrate two different cell types by immunocytochemistry and/or electron microscopy. The D1 cell was identified as the source of HPP in tumours.


Interaction between ceruloplasmin and Sendai virus envelope components. Note i. Gel-filtration of Tween 20-solubilized envelope components. Sindai virus was disrupted by treatment with different concentrations of Tween 20 in an alkaline medium and the variations in infectivity, turbidity, hemagglutinin, neuraminidase and hemolytic activities were followed up. Gel-filtration of virus envelope fragments obtained by disruption with 1% Tween 20 demonstrated their heterogeneity as regards shape, size and biological activity. The elution type, the ratio between hemagglutinin and neuraminidase activities and the affinity for red blood cells of the envelope fragments depend on the detergent concentration used for virus disruption and on the presence or absence of detergent in the eluent.


Interaction between ceruloplasmin and Sendai virus envelope components. Note ii. Some characteristics of Tween 20-solubilized envelope components isolated by gel-filtration. Biological activities of Tween 20-solubilized Sendai virus envelope differ according to the structure of the components obtained, which depends on: conditions of virus disruption, presence or absence of detergent during gel-filtration, duration of maintenance, type of fragments contained in the samples, and can be correlated neither with the size of fragments, nor with protein concentration.


[Concentration of cytoplasmic RNA in the endometrium in trophoblastic disease]. The method of cytospectrophotometry was used to determine quantitatively the content of cytoplasmatic RNA in cells of endometrial glands in 28 females who suffered trophoblastic disease. It was found that during the first year after the disease the RNA content in the endometrium in patients, subjected to chemotherapy, was nearly twice as low as in females not treated with methotrexate. Within the same period the RNA content was mostly low in those, who suffered malignant forms of the disease and were injected larger doses of the substance, accordingly. If the duration of the disease was longer than a year, the RNA content in the endometrium in both methotrexate treated and not females proved to be nearly the same, in the former the content being reliably higher than the analogous value in the control group (10 females in a phase of normal menstrual cycle secretion not suffering hydatid mole). During the investigation a correlation was found between changes in the endometrial RNA content and the level of sex hromones excretion.


[Mechanism of the antitumor action of 1,6-di-o-methane-sulfonide-2,3-4,5-dianhydro-1-iditol]. Under study was the effect of the drug in question on the growth of ascitic tumor NK/Ly. The drug, depending on its dosage, was found to suppress the tumor growth both in its accelerated and delayed stage of development and to show an instant effect. Its efficacy in the dosage employed would have no stage selective character. DMDAI blocks DNA synthesis and presumably impairs the metabolism of RNA ingradients, playing an important role in the mitosis and synthesis of DNA.


[Characteristics of the clinical picture and prognosis of insulinoma]. A case with insulinoma is reported, with initial malignant degeneration, diagnosed and operated 16 years ago. Six years later hypoglycemic attaks appeared again and lymph metastasis in good health a third surgical operation was performed because of repeated hypoglycemic attacks and a new metastasis from the insulinoma was found in the pancreas tail. The patients has no hypoglycemic phemonena 18 months after the last operation. Besides the long period of progress of the malignant degenerated insulinoma, not observed so far, certain peculiarities of the carbohydrate metabolism of that patient are stressed upon as well as the necessity of early diagnosis and timely surgical treatment of insulinoma.


Seroimmunity of adult Ghanian hospital staff and their wards to poliomyelitis. The antibody content of sera collected from 104 adult staff of the Korle Bu Teaching Hospital and 16 of their wards were studied by microtitre neutralization test to poliovirus types 1, 2 and 3. The immune status of the study population was highly satisfactory; there was only one (0.83%) out of the 120 persons studied without antibodies to all three poliovirus types. The percentage of sero-positive subjects to the individual poliovirus types, that is 1, 2 and 3 were 75.83%, 70.00% and 86.16% of the study population. Immunity in relation to age was also studied.


Testing of antiviral compounds against Mengo virus infection of mice. A 2-step procedure of in vivo screening. A 2-step procedure of screening of antiviral compounds in vivo is presented on the basis of standardized methods of both experimental examination and statistical analysis. The procedure uses the "rate of protection" R as the sole criterion of activity. In the first step, requiring a total of 40 mice, compounds with significant R are detected. Drugs producing R less than 15% are discarded. Compounds eliciting R larger than or equal to 15%, without significance, are examined in a second step, using again 40 mice, to decide whether the protective activity becomes significant employing a greater number of animals. The procedure works with relatively less expense with regard of the number of animals used and the time required. The procedure can be applied to test systems based on lethal infections as well as to test models for which the use of the "rate of protection" is relevant.


Characterization of a stable spheroplast type L-form of Proteus mirabilis D 52 as cell envelope mutant. II. Electronmicroscopic investigations. The ultrastructural analysis of a stable spheroplast type L-form of Proteus mirabilis D 52 revealed characteristic alterations in the organization of the cell envelope including defective changes in the cell envelope structure as for instance the loss of a coherent murein layer, the loss of some components in the outer cell wall layer, the formation of small membraneous vesicles at the tips of loose extensions of the cell wall, a decrease in associations and bindings between wall and membrane, an extension of the periplasmic space, an increase in membrane defects, as well as a disturbed cell division causing unusual modes of multiplication and the formation of various intracellular structures like membrane complexes, characteristic sheet-like membraneous bodies, typical inclusion bodies, and defective phage structures, which all could not be observed in normal rod-shaped cells. The results of these investigations and of those given in a previous paper (Gumpert and Taubeneck 1975) show, that the stable spheroplast type L-form LD 52 B must be considered as a true cell envelope mutant in which the biosynthesis and structure of the cell envelope is altered genetically by one or several mutations whereas the main biochemical activities are the same like those of the parent bacterium. The profound alterations in the cell envelope system, however, lead to some changes in the whole cell organization, which apparently in turn cause disorders even in metabolic and biosynthetic processes not directly involved in the biosynthesis of the cell envelope.


[Biokinetic behavior and metabolic effect of fructose in high dose continuous infusion in the rat]. The steady-state blood level of fructose during 24 hours intravenous infusion in response to different doses follows saturation kinetics. Even after toxic doses of 1.5 g/kg/h no depletion of liver adenine nucleotides can be observed after 24 hours. In the kidneys, however, ATP, ADP and total adenine nucleotides were decreased after a dose of 1.5 g/kg/h of fructose. The blood glucose increased continuously at infusion rates of 1.5 g/kg/h. Inorganic phosphate in the blood increased at doses of 1.0 and 1.5 g/kg/h. The weight of the kidneys increased, presumably through water uptake. Urinary secretion was drastically reduced at doses above 1.0 g/kg/h. An appreciable activity of ketohexokinase can be demonstrated in the kidneys.


[The diagnostic importance of low-density lipoprotein (LP-X) for the diagnosis of cholestasis]. Based on the clinical, biochemical and morphological examination of a selected group of patients, the following may be said about low-density lipoprotein (LP-X): The LP-X test 1. proves to be a reliable method of examination for diagnosing cholestasis. It is a quick and simple test; 2. has a highly significant statistical relationship (x2 = 31,7) to the histological results and other parameters indicating cholestasis; 3. does not, however, distinguish between intra- and extrahepatic cholestasis and positive results do not allow any conclusion as to the etiology of the icterus; 4. makes it possible to diagnose cases of cholestasis with aP activities not clinically manifest; 5. in borderline cases conclusions may be drawn from a combination of LP-X and aP results and, most of all, from LP-X and gamma-GT, a highly sensitive, specific and simple method of diagnosis. 6. diagnostic findings of still greater significance resulting from applying laboratory data indicating or precluding cholestasis may be derived from a prospective study with a larger group of patients, using the same parameters and taking the likelihood ratio into consideration.


[Cytoid bodies in basal cell epithelioma]. 100 basal cell epitheliomas were surveyed for the presence of cytoid bodies by histological and histochemical techniques. By this means a differentiation of the following structures was possible: 1. Elastic globes were present in 32 specimens. Their localisation corresponded in part to the typical subepidermal situation, but invasive tumor growth resulted in their translocation into the deeper corium. 2. Civatte bodies were found in the dermoepidermal junction area in 16 cases. Similar structures were present within the tumor cell islands of 37 patients. 3. Russel bodies could be observed within the inflammatory peritumoral infiltrate containing numerous plasma cells in 30 specimens. 4. Clumpy or ovoid deposits of amyloid were present within the stroma of 41 epitheliomas, whereas no amyloid was found in the tumor cell islands.


[Action of a new synthetic ACTH drug in psoriatic arthropathy]. In light of observations in 10 patients the author reports the results of a course of therapy with synthetic depot tetracosactide (SYNACTHEN DEPOT) in psoriatic arthritis. In 2 patients no improvement was evident, while in 3 patients temporary improvement was observed but the effect of the drug was inadequate except in combination. In 5 patients, following intramuscular administration of 1 mg without any other medication, improvement in the symptoms and the objective articular findings, where ankylosis was not present, was observed within a few hours and this improvement lasted for more than one week.


[Serum beta-lipoproteins following gynecologic surgery]. Authors have watched the changes of concentration of betalipoprotein after gynecological operations, on a large group of patients. The task of this work was to prove the existence of postcastration dyslipoproteinaemia, which had been proved in a smaller group by complex laboratory method. They have proved, using the Burstein's method, the development of dislipoproteinaemia in a larger number of vases after operation with bilateral ovarioectomy.


[Anatomical and clinical deliberations on the phyllodes tumor of the breast]. The authors report on three phyllod Tumours of the breast, two benign and one malignant conditions. They insist on the histological aspect of the tumour, underlining that in the benign forme both, epithelial and mesenchymal components does not present atypies, while in the malignant form only the mesenchymal component gets malign sarcomatous character. The microscopic aspect of the tumour and its clinical evolution are suspicious. The diagnosis can be specified only by the histopathological examination. The origin of the phyllod tumour is not clear and the authors discuss the possibility of its development upon a preexistent tumour, specifically on a fibroadenoma of the breast. The treatment is guided by the microscopic appearances. Generally they perform the ablation of the tumour when its dimensions are not greater then 10 cm. and the simple mastectomy when its diameter exceeds this dimension.


[Immunologic reactions to tissue antigens in patients with different stages of cerebral atherosclerosis]. The results of the conducted studies testify to the existence of a certain correlation between the stage of the pathological process and immunological reactions to brain antigens and vessels in patients with cerebral atherosclerosis. In the I and II stages of cerebral atherosclerosis there is a certain predominance of seropositive reactions to brain beta-lipoproteids. In transient disorders of brain circulation there were prevalent reactions to water soluble proteins of the vascular tissue. In patients with residual symptoms of ischemic strokes the most frequent findings were seropositive reactions to brain proteins and beta-lipoproteids.


On the selectivity of aryl hydrocarbon hydroxylase induction after 3-methylcholanthrene pretreatment. The development of aryl hydrocarbon (benzo(a)pyren)hydroxylase (AHH), succinate dehydrogenase and glucose-b-phosphatase activities in the liver and the kidney and of liver weight and glycogen were investigated in 7-day-old rats treated i.p. with 1, 10, and 100 mg 3-methylcholanthrene (MC)/kg body weight. 3-MC highly specifically influenced the AHH activity, which was increased dose dependent. The higher the dose, the higher and the longer was the induction effect. The other biochemical parameters investigated were not influenced. At the maximum of the induction effect after pretreatment with the highest dose of 3MC no morphological alterations in the liver could be observed by light and electron microscopy. Therefore the 3-MC mediated AHH induction seems to be a suitable model for the examination of dose dependent inducer-inhibitor interactions in the intact animal.


Evidence for cyclic AMP-dependent protein kinase activity in isolated guinea pig and rat liver mitochondria. Purified preparations of guinea pig and rat liver mitochondria contain considerable latent cAMP-dependent protein kinase activity that is revealed by treatment with 1% Triton X-100. The solubilized kinase was partly purified by DEAE-cellulose chromatography. It accepts protein in the washed Triton-extracted mitochondria as substrate.


[Spectroscopic investigatons on the structural thermal stability of leucine aminopeptidase. ESR, CD and fluorescence studies]. The thermal behaviour of leucine aminopeptidase (LAP, EC: 3.4.11.1) from bovine eye lens has been investigated in the temperature region 20--70 degrees C by spin-labelling of SH-groups (ESR), by CD and by fluorescence of tryptophane residues. Enzymatic activity of LAP was compared with spectroscopic data in this temperature region. From 20-60 degrees C the structural parts (alpha, beta, random coil) estimated from CD spectra remain unchanged. Within 20-55 degrees C no irreversible exposure of tryptophane residues takes place. In both types of spin-labelled LAP the strong immobilizing environment of the label retains its highly ordered structure up to 55 degrees C. Reversible changes of mobility and polarity of the environment of the label induced by temperature within 20-50 degrees C do not reduce the enzymatic activity and are regarded as local loosening of ordered structure. At 65 degrees C strong precipitation occurs. From 55 degrees C to 65 degrees C tryptophane residues are irreversibly exposed. The highly ordered environment of the label is destroyed about 55 degrees C, and a considerable amount of spin label molecules is reduced at the NO group by exposed SH groups. The above mentioned local loosening of structure becomes irreversible at 60 degrees C. The environment of both labels dominating above 60 degrees C is highly mobile and strongly polar and represents an extensively unfolded conformation. Until 60 degrees C no essential disordering of protein structure leading to a decrease of enzymatic activity occurs. Above 60 degrees C a sharp breakdown of ordered structures takes place, which is accompanied by a strong diminution of enzymatic activity.


Dissociation and rate constants of some human liver alcohol dehydrogenase isoenzymes. ADH from human liver forms binary complexes with NADH, associated with a blue shift of the peak of the fluorescence emission of NADH. The wavelength shift is the same for all isoenzymes but the accompanying intensification of the fluorescence is different. The fluorescence is further increased by the formation of the very tight ternary enzyme-NADH-isobutyramide complexes. These properties are similar to those for the horse liver ADH, as well as the molecular weight of E=40 000 per active site of the dimer molecule (EE). "Stopped-flow" determined velocity constants (ER in equilibrium E+R) were found to be in good agreement with ethanol activity constants previously determined by activity measurement, confirming the validity of the ordered ternary complex mechanism also for the human ADH. No single isoenzyme activity as high as that reported by Mourad and Woronick or Drum has been found.


Medullary thyroid carcinoma: ectopic production of peptides with ACTH-like, corticotrophin releasing factor-like and prolactin production-stimulating activities. A 45-year-old women had medullary tyroid carcinoma associated with Cushing's syndrome and galactorrhoea. Elevated plasma immunoreactive ACTH and cortisol were partially suppressed by intravenous dexamethasone, appreciably raised by lysine vasopressin, and urinary excretion of 17-oxogenic steroids slightly elevated by metyrapone. A large arterio-venous increase in plasma corticotrophin releasing factor-like activity across the thyroid gland was observed and tumour tissue contained corticotrophin releasing factor-like activity. Biologically active ACTH was not detected in tumour extracts before incubation with trypsin, but after trypsinization a value of 3.2 mU per gram was obtained. Arterial plasma contained biologically active ACTH (1.5 mU/100 ml) prior to trypsinization. Venous effluent from the thyroid gland contained biologically active (9.6 mU/100 ml) and immunoreactive ACTH (970 pg/ml) before trypsinization. Tumour extracts also contained prolactin production-stimulating activity. These findings can explain the Cushing's syndrome and the galactorrhoea both of which disappeared completely after thyroidectomy.


Action of KI, thyroxine and cyclic AMP on [3H]uridine incorporation into the RNA of thyroid slices. Potassium iodide (KI) has been shown to impair thyroid protein biosynthesis both in vivo and in vitro. The present study was performed in order to clarify its mechanism of action. Ribonucleic acid (RNA) synthesis was studied in beef thyroid slices with either [32P] or [3H]-uridine as labelled precursors. Both KI and thyroxine (T4) at 10(-5) M significantly decreased RNA labelling under our conditions. In other experiments RNA degradation was examined in pulse-labelled and actinomycin D-treated slices. KI did not modify the degradation of the [3H]-RNA thus indicating that it interferes with the biosynthesis rather than with the degradation of RNA. Taking the perchloric acid soluble radioactivity as a rough index of the precursor pool the present results would indicate an action at this level. Both KC1O4 and methylmercapto-imidazole relieved the gland from the inhibitory action of KI, supporting the view that an intracellular and organified form of iodine is responsible for this action. Since T4 also reproduced the effects of KI on RNA synthesis we would like to propose iodothyronines as the intermediates of this action. Cyclic AMP has been shown to stimulate thyroid protein biosynthesis. The present results demonstrate an action at the RNA level. Cyclic AMP increased both the PCA-soluble and RNA-linked radioactivity, thus suggesting an effect at the RNA precursor pool. KI at 10(-5) M blocked the action of 2 mM cyclic AMP.


Preliminary observations of bovine adrenal fasciculata-reticularis cells in monolayer culture: steroidogenesis, effect of ACTH and cyclic AMP. Bovine adrenocortical cells dispersed by trypsin digestion of fasciculata-reticularis minces were maintained in monolayer culture for up to 6 weeks. During the first week cells grown in medium containing ACTH (1 mU/ml) secreted steroids at a rate 10 to 20-fold greater than control cultures, cortisol accounting for 80-90% of the corticotrophic response. Using tracer amounts of [3H] progesterone and [3H] pregneolone, the major products were cortisol, corticosterone, 11-deoxycortisol and 11-deoxycorticosterone in decreasing order of magnitude. After 10 to 15 days in culture steroidogenesis was no longer enhanced by ACTH. This was concomitant with an apparent loss of 11 beta-hydroxylase activity which was mainly manifested by a sharp increase in the formation of 44-deoxycortisol. Short-term incubations of these cells during the first week in culture provided evidence that steroidogenesis was related to ACTH concentrations (from 0.1 to 100 muU/ml) and stimulated by dibutyryl cyclic AMP, the corticotrophic responses being further enhanced by theophylline (0.5to 50 mumoles/5 ml). Exposure of the cells to ACTH (50 muU/ml) resulted in a rapid increase in intracellular cyclic AMP contractions concomitant with a progressive increase in the corticosteroids released into the medium.


Granulocyte function in untreated acute and chronic granulocytic leukemia. Untreated patients with acute granulocytic leukemia showed impairment of microbicidal activity and,, in one, this was associated with myeloperoxidase deficiency and staphylococcal infection. In chronic granulocytic leukemia, there was no significant impairment of microbial killing. However, reduction in the capacity to reduce nitro-blue tetrazolium indicated some disturbance of neutrophil function in this disorder.


Cytoenzymology of benign and malignant tumours of the corpus uteri. I. Respiratory enzymes. The activity of a group of respiratory enzymes was studied in normal menopausal as well as benign and malignant tumours. A decrease in the activity of succinic dehydrogenase, diphosphopyridine nucleotide diaphorase and cytochrome oxidase in malignant tumours especially in spindle cell sarcoma and undifferentiated adenocarcinoma was observed. Benign tumours manifested variable results, thus cellular fibromyoma showed no changes in the activity of succinic dehydrogenase, diphosphopyridine nucleotide diaphorase and cytochrome oxidase whereas fibromyomal cells exhibited less enzymatic activity. In addition, no marked difference was observed in the activity of glucose-6-phosphate dehydrogenase in the aforementioned tumours as compared with normal menopausal uterine tissues.


The reactions of rabbit gall bladder epithelium to electron microscopic stainings for carbohydrates with 1,2-glycol groupings. In the rabbit gall bladder epithelium several ultrastructural elements have been reacted positively for different electron microscopic stainings for carbohydrates with 1,2-glycol groupings. These elements include the surface coat of the plasma membrane, pinocytotic vesicles, certain elements of the Golgi apparatus, secretory granules, lysosome-like bodies and glycogen particles. These ultrastructural elements were found to vary in reactivity with different staining procedures for the demonstration of the carbohydrates. Attempts were made to correlate the positive reactions of some of these carbohydrate-containing elements with their cytophysiological functions, and the varying reactivity of the carbohydrate-containing elements with different staining methods was discussed in relation to factors involved in the staining reactions concerned.


Ultrastructural study of the adenohypophysis of the Chinese hamster. The adenohypophysis of normal Chinese hamsters of both sexes was examined ultrastructurally. Organs were fixed by intravascular perfusion with S-collidine-buffered glutaraldehyde solution. Seven types of cells were differentiated and, according to morphological characteristics, classified as (1) mammotropes, with very large (400-800 nm) polymorphous secretory granules; (2) somatotropes, either in the storage phase with numerous large, dense granules (average 300 nm), or in the hormone synthesis phase, with abundant endoplasmic reticulum and large Golgi apparatus; (3) corticotropes, with irregular cell shape, and granules (average 160 nm) arranged in lines parallel to the cell membrane; (4) FSH gonadotropes, with abundant and dilated endoplasmic reticulum, and granules (190-320 nm) uniformly distributed in the cytoplasm; (5) LH gonadotropes, with granules (120-220 nm) of varied density; (6) thyrotropes, with irregular cell shape and very small granules (120-160 nm), and (7) agranulated cells. The ultrastructure of the adenohypophysis of the Chinese hamster corresponds closely with observations reported in rats, mice and Syrian hamsters.


Medulloblastomas and other neural tumours in mice treated neonatally with N-ethyl-N-nitrosourea. Newborn mice of four inbred strains were injected with a single dose of N-ethyl-N-nitrosourea. The wide range of tumours induced included a small number in the central and peripheral nervous systems. The 4 brain tumours all arose in the cerebellum. Three in one strain were medulloblastomas showing continuity with the internal granular layer. All three tumours showed diffuse infiltration through the molecular layer and continuity with densely-packed islets of cells that marginated immediately beneath the pia and closely resembled remnants of a persistent fetal external granular layer. The medulloblastomas are discussed with special relevance to the histogenesis of the equivalent tumour in man.


Infantile neuroaxonal dystrophy. Ultrastructural study of peripheral nerve. Ultrastructural study of the biopsied sural nerve in a case of infantile neuroaxonal dystrophy was made. The characteristic change in the ballooned axons is an accumulation of membranous profiles associated with mitochondria, glycogen like granules, dense bodies, vesicles and electron lucent material. The membranous profile is classified into three morphological types and discussed on each of them. Probably tubulomembranous profile of the first type is most common and may be cardinal deposit in this condition. These membranous structures of various types might be, however, only different manifestations occurring on the same morbid process. Enormous amount of glycogen like granules and mitochondria might be related to the metabolic derangement of carbohydrate in the ballooned axons. Electron lucent material we observed was not described in the previous papers on this condition. We added one more example showing that nerve biopsy is helpful to confirm the diagnosis in infantile neuroaxonal dystrophy.


Dense core mitochondria in peripheral ganglia of man. Neuronal perikarye of peripheral ganglia contained unusual dense core mitochondria that were not seen in other cell types or tissues of the same individual. They were found in several patients autopsied with GM1-gangliosidosis and neuronal ceroid-lipofuscinosis. Previous observations on human sympathetic ganglia, obtained by biopsy, and our findings suggest that these dense core mitochondria might represent a rare but regular feature of neuronal perikarya in peripheral ganglia of man.


Effects of topical glucocorticoid medication on collagen biosynthesis in the dental pulp. The aim of the study was to observe pulpal collagen synthesis in response to trauma and to glucocorticoid medication. The material consisted of 290 rabbit pulps and 76 human premolar pulps. Collagen synthesis was determined by incubating whole pulps in a medium containing [14C]proline, and measuring the formation of [14C]hydroxyproline. The effect of glucocorticoids was studied in vitro using rabbit pulps. Hydrocortisone and dexamethasone inhibited collagen synthesis, whereas prednisolone had no marked effect. Hydrocortisone was found to inhibit the synthesis of [14C]hydroxyproline in neutral salt soluble and insoluble non-dialyzable collagen fractions. [14C]hydroxyproline in the dialyzable fraction was increased, suggesting that hydrocortisone increased collagen degradation. In the human material, premolar pulps were experimentally exposed and then medicated with capping agents. The contralateral teeth were exposed and capped with other capping materials, in some cases they were left as intact controls. The exposure led to an increase in the collagen synthesis as indicated by increased [14C]hydroxyproline formation and elevated protocollagen proline hydroxylase activity in the pulp. This enzyme activity was suppressed in pulps capped with a glucocorticoid paste. In addition, the collagen synthesis rate was lower in pulps treated with another glucocorticoid containing compound, when compared to pulps capped with a calcium hydroxide preparation.


[ACTH therapy and peritumoral oedema (author's transl)]. Out of the various drugs which may be used in the treatment of intracramial hypertension we have tested long-acting Synacthen (Synacthen-dépot) in patients with inoperable cerebral tumours. The results were favourable, especially in the case of long-term treatment, since the delayed action of the drug allows flexible application while ensuring significant comfort for the patient.


Human interferon and cell growth inhibition. I. Inhibitory effect of human interferon on the growth rate of cultured human cells. Human interferon inhibited the growth rate of cultured human cells. These included diploid fibroblast cells from embryonal lung and skin, established lines of HeLa and U-amnion cells, all grown in monolayer; and the established lymphoblastoid line P3HR1 grown in suspension. Cells growing fast were inhibited to a higher degree than those growing slowly. The inhibitory effect was dose dependent but the dose-dependency was different in various cell types. The inhibitory effect of leukocyte interferon and fibroblast interferon was quantitatively comparable.


Effects of secretagogues on oxygen consumption, aminopyrine accumulation and morphology in isolated gastric glands. A recently developed method to isolate gastric glands from the rabbit gastric mucosa (Berglindh and Obrink 1976) was used to study the effects of some common gastric secretagogues. Three parameters were investigated: 1) Respiratory activity; 2) Intraglandular accumulation of the weak base aminopyrine; 3) Quantitative morphology of the parietal cells. The following substances were tested: Histamine, cAMP, db-cAMP, aminophylline, carbachol and pentagastrin. The strongest effect was obtained with db-cAMP which dose-dependently stimulated the respiration up to 200%, increased the aminopyrine accumulation 80% and altered the parietal cell morphology from a typically resting to a typically stimulated state. cAMP also stimulated the respiration but was about 10 times less effective on a molar basis than the dibutyryl form. Histamine, like db-cAMP, stimulated the respiration in a dose-dependent manner and strongly increased the aminopyrine accumulation. The morphological changes were, however, not of the same magnitude as after db-cAMP. Aminophylline, tested only for respiratory activity, stimulated the oxygen consumpation moderately. Carbachol induced a transient increase in both the oxygen consumption and in the aminopyrine accumulation with a peak value after approximately 15 minutes for both, but gave no significant morphological alterations. Pentagastrin, finally, was incapable of inducing changes in any of the three parameters. Aminopyrine was also found to accumulate approx. 50 times in unstimulated, morphologically resting glands. This seems to indicate that there might be acid sites already in resting glands.


Effect of glucagon on cyclic AMP, albumin metabolism and incorporation of 14C-leucine into proteins in isolated parenchymal rat liver cells. Parenchymal rat liver cells were isolated by the collagenase method and incubated in Krebs-Henseleit buffer containing 0.5% gelatin. The basal level of cyclic AMP in isolated cells was 0.52 nmol per g liver wet wt. Glucagon (10(-10)-10(-6) M) caused a significant increase in the level of cyclic AMP. Maximum levels were obtained 2-15 min after addition of glucagon. Repeated administration of glucagon caused a new increase in cyclic AMP, but the response was lesser than after the first addition of glucagon, indicating refractoriness to glucagon. The rate of albumin secretion was 4.6 mug/min per g liver wet wt. This is about the rate found in the perfused liver, Glucagon (10(-8-10(-6) M) inhibited albumin secretion and the incorporation of 14C-leucine into albumin, into total proteins in the medium and into total proteins in the cell suspension. The effect of glucagon on albumin secretion is compatible with an effect on the rate of synthesis. A positive correlation existed between the maximal level of cyclic AMP after glucagon administration and the inhibition of both albumin secretion and the incorporation of 149leucine.


Effect of adrenaline on the release of cyclic AMP by the rat diaphragm. An investigation was made of the effect of adrenaline on the tissue level and release of cyclic AMP (cAMP) into the incubation medium by the isolated rat diaphragm preparation. Adrenaline, added in vitro, caused a dose-dependent biphasic increase in the tissue level of the nucleotide. A significant elevation of the level of cAMP in the tissue was observed throughout a 60 min incubation period in the presence of 0.01, 0.1 and 10 mug/ml of adrenaline. The hormone also produced a small but significant increase in the release of cAMP into the incubation medium. The accumulation of cAMP in the incubation medium ceased after 10 min of incubation in the presence of adrenaline, although the tissu e level of the nucleotide remained considerably elevated throughout the entire incubation period. Theophylline potentiated the effect of adrenaline on both the accumulation of cAMP in the tissue and in the incubation medium. Theophylline by itself also increased the tissue level of cAMP slightly. It is concluded from the present study that the elimination of cAMP from the rat diaphragm muscle by release of the nucleotide from the cells is small.


Treatment of metastases in nephroblastoma. A series of 36 children with nephroblastoma treated between 1966 and 1973 was analysed. None of the patients with stages I or II and microscopic type I or II developed metastases; 5 of 7 patients with stages I or II and microscopic type III developed metastases. All patients in stage III developed metastases. Fifteen patients developed metastases after the termination of the primary treatment. Of 9 patients with pulmonary metastases only, 6 are free of disease, all patients with metastases in other sites are dead.


Macrophage migration inhibition-activity after implantation of methylcholanthrene-induced sarcoma, Ehrlich ascites cancer or mouse ascites hepatoma-134 cancer cells in mice. Cells from methylcholanthrene-induced tumor (MC-tumor), Ehrlich ascites cancer or mouse ascites hepatoma (MH-134) were subcutaneously implanted in dorsal area of mice to examine the specific cell mediated immunity following implantation. The migration index (MI) of lymphocytes was determined at various time periods after cell transplantation. The MI-activity increased under all three implantations, reached maximum at a certain period, decreased gradually and disappeared. The maximum MI-activity coincided with the proliferation period of the implanted tumor cells. This peak occurred on the tenth postimplantation day with MC-tumors, on the fifth day with Ehrlich ascites cancer and on the sixth day with MH-134 cancer. In lymphoid tissues of animals with MC-tumor and Ehrlich ascites cancer, strong MI-activity appeared early in the regional axillary lymph nodes, while weak activity was observed consistently in the distant mesenterial lymph nodes. The MI-activity of the splenic lymphoid cells resembled the axillary lymph nodes cell activity. The MI-activity of venous blood lymphoid cells was parallel to the average value of lymphoid cells of the spleen and axillary and mesenterial lymph nodes.


Immunoreactive insulin in portal and hepatic venous blood in patients with insuloma. The insulin level has been determined simultaneously in portal and hepatic venous blood in four patients with insuloma before and after administration of glucose and tolbutamide. Three patients displayed a higher insulin level in hepatic than in portal blood, although no hepatic metastases could be detected by radiologic examination. In contrast, portal insulin concentrations always exceeded hepatic in four control patients investigated in a similar way. The implications of these results are discussed.


Relationship between intracellular cyclic AMP and lipolysis in human adipose tissue. Human subcutaneous adipose tissue has been incubated in vitro in the presence and absence of isoprenaline (ISNA). The tissue concentration of cyclic AMP (cAMP) and the release of glycerol into the incubation medium were measured after various incubation periods. In the presence of ISNA (6 X 10(-5) mol/l), the tissue concentration of cAMP reached a peak after around 10 min and then declined to a level significantly lower than that at the start of the incubation. In contrast, the ISNA-induced rate of lipolysis was a linear function of the incubation time. The addition of propranolol (13 mumol/l) at different times after ISNA did not influence the rate of lipolysis, although it resulted in a decrease in the tissue level of cAMP. There was a positive correlation between the maximal increase in tissue cAMP and the rate of lipolysis in adipose tissue exposed to ISNA, both in individual experiments and in a group of 23 persons. No correlation was found between the rate of lipolysis and the tissue level of cAMP in adipose tissue incubated under basal conditions. The findings are compatible with the theory that the beta-adrenergic-induced lipolysis by human adipose tissue is a function of the maximal rise in the concentration of tissue cAMP. It is concluded that this peak level of cAMP represents single compartment of the nucleotide.


Metabolism of mono- and diacylglycerols in subcutaneous adipose tissue of obese and normal-weight subjects. Tissue monoacylglycerols (MG), diacylglycerols (DG), free fatty acids (FFA), and cyclic AMP (cAMP) and release of FFA and glycerol have been studied in vitro in subcutaneous adipose tissue of 6 obese and 7 normal-weight subjects. The tissue was incubated without or with 6 X 10(-5) mol/l of isoprenaline (ISNA). The DG level and the fat cell volume were strongly interrelated (r=+0.95,  p less than 0.001). The concentration of DG was increased (p less than 0.05) in obesity. The changes in DG and MG were significantly interrelated (r=+0.65, p less than 0.05) during basal incubation. ISNA increased the DG concentration in a way that was correlated (r=+0.81, p less than 0.001) with the ISNA-induced glycerol release. This indicates that 1) the basal metabolic activities of MG and DG lipase are similar and 2) DG lipase is an important rate limiting factor in lipolysis. Without ISNA, tissue FFA and the release of FFA and glycerol were significantly increased in the obese patients. As a mean, MG and DG did not accumulate in the basal state in the two patient groups. The findings indicate that basal lipolysis was increased in obesity. This was probably due to increased basal metabolic activity of triacylglycerol lipase, since the basal cAMP levels were similar in the two patient groups. In the presence of ISNA, the production of FFA and the glycerol release were similar in both patient groups, as was the increase in tissue DG. Also the ISNA-induced maximal level of cAMP was similar in the two groups. With ISNA, a small increment of MG was observed in adipose tissue of the normal-weight subjects. Taking all metabolites into account, the rate of lipolysis as well as the activation of triacylglycerol lipase via cAMP in the presence of ISNA appeared to be unaltered in obesity. Separate experiments with 1-14C-glycerol provided further evidence for the existence of a MG pathway for the esterification of FFA.


Urinary cyclic AMP. Relation to albumin-corrected serum calcium in healthy persons and patients with primary hyperparathyroidism. In 21 healthy volunteers, mean excretion of cyclic adenosine 3',5' monophosphate (cAMP) in urine was 4.2 +/- 1.0 (S.D.) mumol cAMP/24 hours, 3.0 +/- 1.2 mumol/g creatinine and 3.8 +/- 1.2 mumol/24 hours/100 ml/min renal clearance of creatinine (CCr). An inverse correlation exists between the excretion of cAMP and serum calcium corrected for variations in serum albumin, most clearly demonstrated when cAMP is expressed as mumol/24 hours/100 ml/min of CCr (r=-0.630, p less than 0.01). In 21 patients with operatively verified hyperparathyroidism, the mean urinary excretion of cAMP/24 hours was 5.0 +/- 1.9 mumol uncorrected, 4.8 +/- 1.8 mumol/g creatinine and 6.6 +/- 2.1 mumol/100 ml/min of CCr. The latter two of these parameters differ significantly from the normal group (p less than 0.001), but conceal the fact that many patients with hyperparathyroidism excrete normal amounts of cAMP in the urine, independent of the mode of calculation. However, when cAMP is correlated to albumin-corrected serum calcium, this overlap between hyperparathyroidism and normality disappears completely. The results support the concept that cAMP excretion is influenced to a considerable degree by the biological activity of circulating parathyroid hormone. They also indicate that the simultaneous measurement of cAMP in urine and albumin-corrected calcium in serum is a useful aid in distinguishing hyperparathyroidism from the state of normality.


Allosteric enzyme-tRNA complexes as regulators of transcription or translation. The dehydrogenase activity of chorismate mutase-prephenate dehydrogenase, the allosteric enzyme of the tyrosine biosynthetic pathway in Escherichia coli, is inhibited by tRNA. The inhibitory effect of tRNA from E. coli is specific, other RNA species or polynucleotides have no inhibitory effect or only slightly influence the activity of the enzyme. While NAD only slightly influences the inhibitory effect of tRNA from E. coli, prephenic acid at high concentrations suppresses the inhibition. In he presence of a fixed concentration of NAD and low concentration or absence of prephenic acid the inhibitory effect of tRNA is time and temperature dependent. It seems that in the presence of tRNA and low concentration of prephenate the enzyme undergoes a time and temperature dependent conformational change. This process is reversible and can be influenced by the concentration of prephenic acid, the first precursor of the tyrosine biosynthetic pathway. The possible regulatory role of allosteric enzyme-tRNA complexes is discussed.


Haemorrhagic and inflammatory properties of collagenase from C. histolyticum. Collagenase from Clostridium histolyticum induced haemorrhages when applied to the surface of dog lung; it exerted a similar effect on mouse lung when injected intrathoracically. Injected into rat paws, bacterial collagenase induced haemorrhage and oedema. Effects of collagenase were prevented by several procedures that inhibit collagenolytic activity (heating at various temperatures and incubation with metal-complexing agents such as EDTA, penicillamine and dithiothreitol). Protein protease inhibitors, dexamethasone and standard acidic anti-inflammatory drugs had only a slight or no effect on collagenase-induced haemorrhages; dexamethasone and acidic anti-inflammatory drugs blocked collagenase-induced oedema. Inhibition of endogenous kinin-releasing mechanisms by administration of hexadimethrine, a recognized inhibitor of the activation of clotting Factor XII, and depletion of kininogen by administration of carrageenin blocked collagenase-induced oedema. Collagenase did not increase permeability of rat skin vessels, nor did it release potential inflammatory mediators, such as bradykinin or prostaglandins, from plasma or platelets. Bacterial collagenase-induced haemorrhage presumably resulted from enzymatic destruction of membranous structures; at least a portion of the inflammatory response may be due to activation of a kinin-like system.


Electrophysiologic effects of atropine on human sinus node and atrium. Electrophysiologic studies were conducted in 17 patients without apparent sinus node disease before and after intravenous administration of 1 to 2 mg of atropine. Mean values in milliseconds (+/- standard error of the mean) before and after administration of atropine were as follows: sinus cycle length 846 +/- 26.4 versus 647 +/- 20.0 (P less than 0.001); sinus nodal recovery time 1,029 +/- 37 versus 774 +/- 36 (P less than 0.001); mean calculated sinoatrial (S-A) conduction time 103 +/- 5.7 versus 58 +/- 3.9 (P less than 0.001); mean P-A interval 34 +/- 1.5 msec versus 31 +/- 1.5 (P less than 0.05); mean atrial effective and functional refractory periods during sinus rhythm 285 +/- 11.3 versus 238 +/- 7.9 and 331 +/0 11.6 versus 280 +/- 8.6, respectively (P less than 0.001 for both); mean atrial effective and functional refractory periods measured at equivalent driven cycle length 239 +/- 7.7 versus 213 +/- 7.4 and 277 +/- 11.4 versus 245 +/- 9.5, respectively (P less than 0.001 for both). In conclusion, atropine shortened sinus cycle length, sinus nodal recovery time and calculated S-A conduction time. The shortening of atrial refractory periods with atropine implies that vagotonia prolongs atrial refractoriness in man.


Significance of pacemaker recovery time after the Mustard operation for transposition of the great arteries. Pacemaker recovery time corrected for cycle length was measured in 24 patients 6 months to 3 years after the Mustard operation for transposition of the great arteries. This index of sinoatrial (S-A) nodal function was obtained by subtracting the control R-R interval from the first R-R interval recorded after 3 minutes of rapid atrial pacing at the superior vena caval-right atrial junction. Recovery times were compared with those of a control group of 54 children with various forms of congenital heart disease who had not had cardiac surgery and whose electrocardiogram revealed normal sinus rhythm. The longest corrected pacemaker recovery time in the control group was 250 msec. Recovery time was normal (mean 115 msec) in 13 of the 24 patients who had undergone the Mustard procedure and prolonged (mean 472 msec) in the other 11. In 4 of these 11 a junctional escape complex was recorded before recovery of the S-A node. The configuration of the P wave and the development of dysrhythmias in the postoperative follow-up period were compared in patients with a normal and a prolonged corrected pacemaker recovery time. The incidence of dysrhythmias was much smaller in the former group. Normal sinus rhythm after the first postoperative week was noted in 10 (76 percent) of patients with a normal corrected pacemaker recovery time but in only 2 (18 percent) of those with an abnormal recovery time. One patient with an abnormal recovery time died suddenly 26 months after operation in spite of good hemodynamic repair. A prolonged pacemaker recovery time after the Mustard operation for transposition of the great arteries indicated that rhythm abnormalities were likely to develop, but a normal recovery time did not exclude abnormal sinus nodal function.


Pathologic correlations in three cases of bilateral bundle branch disease with unusual electrophysiologic manifestations in two cases. Examination of the conduction system in three patients with bifascicular block who had electrophysiologic studies forms the basis for this report. Patients 1 and 2 had left bundle branch block and Patient 3 right bundle branch block and left axis deviation. The H-V interval was prolonged in each case (70, 65 and 60 msec, respectively). Serial section examination of the conduction system revealed sclerodegenerative involvement of both bundle branches in all cases. In Case 1, atrial extrastimulus testing converted left to right bundle branch block; in Case 2, it delineated a sinus echo zone with repetitive sinus nodal reentrance. In the latter case serial section revealed extensive amyloid infiltration of the approaches to the sinoatrial (S-A) node and the atrial preferential pathways. In Case 3, with right bundle branch block and left axis deviation, serial section revealed greater involvement of the anterior part of the main left bundle branch than of the posterior portion as well as involvement of the second part of the right bundle branch. The study revealed excellent correlation between electrophysiologic and pathologic findings in three cases of intraventricular conduction disease and demonstrated an anatomic basis for the electrophysiologic findings resembling alternating bilateral bundle branch block. Sinus nodal reentrance may be related to disease in the approaches to the S-A node thereby causing delay in perinodal tissue allowing sinus reentrance. Finally in Case 3, the anatomic substrate for left axis deviation may lie in a greater involvement of the anterior portion than of the posterior portion of the main left bundle rather than in the corresponding portions of the periphery.


Intranuclear bodies in neurons of the periaqueductal gray matter in the cat. The nucleoplasm of neurons in the nucleus lateralis of the periqueductal gray matter in the cat contains fibrillar structures which have no limiting membranes. These intranuclear bodies are associated with neither the nucleolus nor the nuclear membrane and have two characteristic forms. The first, the rodlet, is a compact bundle of fibrils 2 to 8 nm in diameter. It is usually elongated in shape although it appears spherical when sectioned transversely. This rod-like structure appears to correspond to Roncoroni's rodlet or the accessory body of Cajal in light microscopy. The second and more commonly observed form is a long slender bundle of five rows of parallel fibrils. Although similar intranuclear structures have frequently been observed in the highly differentiated neurons of the sympathetic ganglia and the retina, this is the first report of their pbesence in the undifferentiated neurons of the isodendritic core of the brainstem.


Serum lipids in alcoholic patients with and without cirrhosis of the liver, with particular reference to endogenous familial hypertriglyceridemia. The purpose of this study was to determine the frequency of hypertriglyceridemia in alcoholic patients with and without cirrhosis of the liver. It had been observed by others that subjects with endogenous familial hypertriglyceridemia (type IV hyperlipoproteinemia) showed an exaggerated lipidemic response to ingestion of alcohol, and, therefore, might be predisposed to hepatic cirrhosis. Comparison of 40 alcoholic cirrhotics with 40 noncirrhotic alcoholic patients showed no increased incidence of hypertriglyceridemia in either group. The findings suggest that the frequency of cirrhosis in the general population is not materially affected by subjects with this metabolic defect.


Cholangiocarcinoma as related to chronic intrahepatic cholangitis and hepatolithiasis. Case report and review of the literature. A case of cholangiocarcinoma is described in a patient with underlying hepatic lithiasis and cholangitis. The possible pathogenesis of cholangiocarcinomas is discussed and the importance of endoscopic retrograde cholangiography in the diagnosis of this malignancy is emphasized.


Acute unilateral adrenal hemorrhage following ACTH administration in a patient with Cushing's syndrome. A patient with Cushing's syndrome and a concomitant unilateral adrenal hemorrhage following ACTH administration is described. Although stress is commonly associated with the onset of adrenal hemorrhage, a pathologically documented adrenal hemorrhage has not been previously in association with ACTH administration in Cushing's syndrome. Repeated doses of ACTH should not be given to patients with Cushing's syndrome as this has little diagnostic value and may lead to adrenal hemorrhage in such patients.


Therapeutic effects of heparin on Pseudomonas-induced corneal ulceration. Fifty organisms of Pseudomonas aeruginosa were injected intralamellarly in both eyes of 60 albino rabbits. Twenty-four hours later, all eyes were graded and stratified into six groups of ten rabbits with equivalent infections. Treatment was begun with gentamicin alone or 0.3% polymyxin B alone, and in combination with acetylcysteine, 0.3M edetate disodium, and 2.500 units/ml of heparin sodium, four times daily. We also compared topical colistin and colistin and topical heparin. After two weeks, those corneas treated with polymyxin B and topical heparin showed a reduction in ulceration, corneal thinning, and descemetocele formation compared to those treated with polymyxin B alone. Based on these studies, heparin was administered topically, four times daily, to three patients with Pseudomonas-induced corneal ulcers in addition to antibiotics. Before treatment all corneas showed evidence of corneal liquefaction and two of the corneas were in imminent danger of perforation. After therapy, no corneas perforated; one patient recovered visual acuity of 6/9 (20/30), one patient recovered visual acuity of 6/6 (20/20) after keratoplasty, and the third has a vascularized leukoma.


Role of atrial receptors in the control of ACTH. Sinusoidal volume changes (+/- 1 ml) were applied at 1 Hz to the right or left atrium of 25 anesthetized cats. Changes in firing rates of single vagal fibers and in plasma ACTH and cortisol were observed in response to start and stop of atrial pulsation. Decreased activity of right atrial and/or septal B-receptors was associated with increased ACTH. Changes in left atrial B-receptor activity were associated with a change in ACTH only if right atrial/septal receptors or baroreceptors also changed their activity in the same direction. The activity of atrial A-receptors did not change in response to atrial pulsation. A quantitative analysis suggested strongly that right atrial and/or septal B-receptors dominate in the response of ACTH to hemodynamic stimuli. Arterial receptors appear less effective, and left atrial B-receptors appear least effective in the hemodynamic control of ACTH.


Identification and discharge patterns of spinal sympathetic interneurons. Sympathetic interneurons, in the vicinity of the intermediolateral cell column of the cat thoracic spinal cord, were identified by determining whether the probability of spontaneously occurring unitary discharge was correlated in time with the R wave of the ECG. Fifteen units which could not be antidromically activated by stimulation of the cervical sympathetic nerve exhivited a positive post-R wave relationship. The discharge patterns of these cells were distinctly different from those of antidromically identified preganglionic neurons. The interneurons discharged spontaneously in bursts with short interspike intervals (less than 20 ms). Preganglionic neurons rarely discharged more than once during a cardiac cycle. Single shocks applied to medullary pressor sites evoked a train of spikes in the interneurons. Preganglionic units usually discharged only once to medullary pressor stimulation. Electrial activation of medullospinal inhibitory tracts suppressed the discharges of both interneurons and preganclionic units. This observation indicates that spinal inhibition is exerted at an interneuronal level within sympathoexictatory pathways. No evidence was found for the existence of inhibitory interneurons in the intermediolateral cell column. This study demonstrated that the post-R wave time interval histogram in combination with a test for antidromic activation can be used to differentiate between spinal sympathetic internuerons and preganglionic cells.


Metabolic intermediates and lactate diffusion in active dog skeletal muscle. The concentration of several metabolic intermediates, blood flow (Q), oxygen uptake (VO2), and lactate release (La) were measured in the gastrocnemius muscle of anesthetized dogs. Muscle lactate concentration increased from 1.6 to 2.7 mumol/g wet wt (P less than 0.05) during 0.5-5 min of contractions at 5 twitches/s but was not different from the contralateral resting muscle at 15, 30, or 60 min. Glycerophosphate increased from 0.35 to 0.70 mumol/g wet wt (P less than 0.05) during 0.5-5 min of activity, whereas muscle pyruvate decreased from 0.09 to 0.07 mumol/g wet wt (P less than 0.05). The concentration of NAD did not change in 9 of 11 experiments during contractions, despite a 12- to 15-fold increase in La. Significant decreases in NAD were observed when Q was compromised by arterial occlusion during contractions. No demonstrable relationship existed between La and either the muscle lactate concentration or muscle-venous lactate concentration gradient. Q was positively correlated with both La and muscle lactate during the first 5-15 min of activity. We conclude that increased La or increased lactate concentration in muscle need not be associated with hypoxia and that Q has a major influence on La.


REM sleep and adaptation of psychiatric patients: an application of sleep studies. The authors used sleep laboratory data to predict responses to psychiatric treatment. The predictions were based on the assumptions that REM latency reflects the need for dreaming and therefore the need for adaptation and that REM time reflects the capacity for the adaptive work associated with REM sleep. Dream recall and dream content were considered indicators of psychological mindedness and the patient's current conflicts. With this material, statistically significant predictions of such outcomes as good response to psychotherapy, elopement, or need for medication were made. The results of this study support the hypothesis that REM sleep is involved in adaptation.


Differential responding to the beta movement after waking from REM and nonREM sleep. Ten young adults were wakened from REM sleep and from nonREM sleep on two nonconsecutive nights and were tested to determine their upper and lower beta-movement thresholds. The ranges of the illusion were found to be significantly wider after waking from REM sleep than after waking from nonREM sleep or before sleep. The differential responding to the beta movement supports the experimental hypothesis that apparent motion may provide sensitive detectors of the operation during wakefulness of the Basic Rest-Activity Cycle, of which REM and nonREM sleep are opposite phases that carry over into wakefulness.


Extensive central nervous system calcification in a stillborn male infant due to cytomegalovirus infection. The radiologic and pathologic findings of a stillborn male fetus with cytomegalic inclusion disease are described. Massive calcification of the cerebrum, cerebellum, eye (sclera and choroid), and spinal cord was present. There were unique deformities and apparent aplasia of some of the ribs. Classic intranuclear cytomegalic inclusion bodies were present primarily in the kidney. Routine radiography of stillborn infants is recommended for further study of intrauterine growth abnormalities.


Scanning electron microscopy of cell surfaces following removal of extracellular material. The application of scanning electron microscopy to the study of cell surfaces is limited in intact tissues, because extracellular material may often obscure the details of nonluminal surfaces. To remove connective tissue elements we have treated human skin and both kidney, and an autonomic ganglion of the rat with hydrochloric acid and collagenase. Regional variations in the basal surface of the nephron are noted following removal of the basement membrane. The basilar interdigitations of the cells of the proximal tubule appeared as parallel ridges encircling the tubule. Ridges on the parietal epithelium of Bowman's capsule were randomly arranged and alternated with smooth surfaces. The dermal surface of the human epidermis has an alveolar or honeycomb appearance due to the elevation of the epidermal ridges and numerous pits for the dermal pegs. At higher magnifications the basal surface of cells of the stratum germinativum possessed numerous and irregular projections. Neurons with their processes are evident in the autonomic ganglion. The soma of the neurons are enclosed by flattened satellite cells. Irregular spaces between opposed satellite cells are interpreted as regions for the passage of processes related to the ganglion cells. Nodes of Ranvier were clearly seen along nerve fibers. Some pitting of the nerve fibers was also noted. The HCl-collagenase method has the advantage of the removal of collagen and basement membrane while preserving the structural integrity of the cell surface.


Studies of the dual effects of halothane on the lipolysis of human fat cells. Halothane has dual effects on lipolysis of human adipose tissue: at low tissue concentrations a stimulatory effect is found, while at higher tissue concentrations lipolysis is inhibited. The lipolytic resonse of human adipose tissue was studied in vitro with or without halothane, the phosphodiesterase inhibitor theophylline, the lipase activator dibutyryl cAMP(dbcAMP), the alpha-receptor antagonist phentolamine, the nonselective beta-receptor antagonist propranolol, and the selective beta1-receptor antagonist practolol. In the absence of beta-receptor antagonists low concentrations of halothane stimulated lipolysis, This effect was blunted by beta-receptor antagonists, indicating that halothane at low tissue concentrations may directly stimulate the beta-receptors. The inhibitory effect of higher tissue concentrations of halothane was not the result of increased alpha-receptor activity since addition of phentolamine did not inhibit this effect. High concentrations of theophylline or dbcAMP increased lipolysis in specimens exposed to halothane, but the lipolytic rate was still less than that found in specimens not exposed to halothane. The data thus indicate that the inhibitory effect of halothane is exerted at a step beyond the formation and degradation of cAMP.