[Spontaneous intraorbital hematoma].

[Spontaneous intraorbital hematoma]. A case of spontaneous intraorbital Haematoma is reported.  A girl aged 13 years developed an acute unilateral Exophthalmos on the right side with disturbances of eye-motion, choked disc and nearly complete amaurosis within 3 days after onset.  The etiology of the bleeding remains unknown.  The diagnosis of orbital haematoma was made by the clinical picture and the computerized axial tomography (CAT) findings.  Through a lateral orbitotomy was the extraperiorbital haematoma evacuated, with a complete recovery within two weeks.  Twenty-two cases of the literature are reviewed.  The possible aetiologic causes are discussed: haemorrhagic diatheses, arterial, vasomotoric and toxic diseases, the congestive and traumatic causes mentioned.  The clinical picture and diagnositc procedures, especially the CAT, are reviewed.  The surgical treatment with stress on the lateral orbitotomy is discussed.


[The 3 phases of schizophrenic psychosis and their phase-specific psychotherapy]. It is not the diagnostic evaluation but merely the phase in which we find our patient, that determines about the process of psychotherapy with schizophrenic patients.  There are three phases--or, more approximately, four phases (phase one to three plus "phase zero")--to be differentiated: Phase Zero: This phase precedes an obvious clinical appearance of psychosis.  Patients feel ridiculous in their anxiety and are not yet capable to create the symptomatology of psychosis.--Intensive participation in those strange perceptions and the attempt to witness the same experiences as the patient does, often help to prevent the formation of a severe psychosis. Phase One: Deep psychosis with common symptomatology. Verbal communication in the usual form is no more possible. Only answering the patient in his own language--speaking as he speaks and behaving as he does--helps to overcome his permanent isolation. Phase Two: Stage where the patient leaves his psychotic world and does not yet live in the world of his "healthy" surroundings.--In this phase psychotherapy intends to lead towards a confrontation with the previous psychotic experiences in order to integrate them into his personality. Phase Three: Phase of return towards a more adequate behaviour.--In this phase the therapist helps his patient to build up his "narcissistic coat" in order to create a shelter, where he can retreat; out of this "cocoon" he is able to observe what happens around him, without being thrown back into a severe psychotic crisis. On the other hand there may arise situations of "relapses" (so-called intermediary stages). These phases, which resemble common depression, can be understood as substitutes of the former psychotic situation. It is insight in its uttermost distinction that leads to secondary stages. Therefore psychotherapy will be most helpful, when the understanding of the circumstances that lead to such situations, is not evaded but promoted; the more intensely these promotions, the better the prognosis.


[Pallido-dentate calcifications (apropos of 7 anatomo-clinical case reports)]. "Fahr's Disease" is characterized by bilateral and symmetrical calcifications of the Globus Pallidus (systematically extending to the Commisura Anterior and the Capsula Interna, and less commonly to the Putamen, the Centrum Semi-Ovale and the Cerebral Cortex), and of the Cerebellar Nucleus Dentalus (with spreading to the White Matter and the Cortical Lamellae). Lesions or absence of Parathyroids are frequently related, with subsequent metabolic disorders of Phosphorus and Calcium, but idiopathic cases without hypoparathyroid disturbances are also found. A Morgagni-Morel Hyperostosis Frontalis Interna is often associated with "Fahr's Disease", and there could be a relationship between these two affections. We found in three cases the association between "Fahr's Disease" and Morel's Nodular Dysgenesis of the Frontal Cortex. Most of the cases are sporadic, but observations with a clear familial incidence are also found. Clinically, various Neurological Disorders (cerebellar, extrapyramidal, pyramidal, dysarthria, epileptic seizures) are often but not always observed; the Psychiatric Disorders found in some cases could be fortuitious associations (psychoses), connected to hypothyroidism (oligophrenia), and in aged patients, to unrelated cerebral vascular or degenerative lesions; very seldom, a dementing state could be connected to the spreading of calcifications to the Cerebral Cortex.


[Social class and mental disorders (an empirical study in Zurich canton)]. The correlation of social class and diagnosis, therapy, mode of admission, frequency of hospitalization was tested in a population of 2103 inpatients of the two governmental and of two private mental hospitals of the Canton Zurich. The results fit to the correlations expected from the literature. The therapeutic procedures as far as reported in the case histories are mainly determined by the hospital type, not so clearly by the subject's social class. High educational status and psychotherapy are correlated. The correlation between social class and therapy is resulting of the class specific admission to one of the two hospital types. There was no sign that within one hospital patients of lower social class were placed at a disadvantage in regard to therapeutic procedures.


[Acute mental disturbances following gynaecological operations (author's transl)]. In the first part acute mental disturbances of more or less psychotic character following upon major gynaecological operations are described. In general there were only minor somatic findings to be made. The mental disturbances were predominantly psychoreactive. They usually disappear under psychopharmacological therapy supporting psychotherapy quickly and do not recur. In the second part the literature relevant to this theme is compared and discussed. The attempt is made to interpret such disturbances as model cases for psychic disorders arising from an interaction between physical and mental components.


[Activity and rehabilitation of senile dementia. Methodological suggestions for an ergotherapy in psychogeriatrics]. The aim of this study is to make clear the conditions of an ergotherapy particularly fit for the aged suffering from senile dementia. It should keep the intellectual instruments in working condition and, eventually, postpone their impairment. The general frame in which theory and experiment are inscribed is the Piaget's theory. Especially the part that concerns the different stages of childhood development of which, one thinks, can be observed the deterioration "in reverse" during the senile dementia impairment processes. Some special hypothesis concern:--the different parts of reality in which relations between patient and society are disturbed --the activities that are connected in a network of relations between the conceptual instruments required to realize these activities --the fact that the steadiness of a particular activity should help to recover another one, thought to be close in the way by which its realization puts into action the same cognitive processes. Thus, we have been able to fix the way of directing a first examination for the taking in charge in ergotherapy; examination that should point out the fields in which the patient can be mobilized (as well from the level where he is as from the investment one can expect in regard to the pleasure or the interest that he shows for a work rather than another). Besides, we tried to represent the channels of activities and their relations, starting from the most elementary one to reach the most complicated one, that is to say the ones that allow us to work on reality. It is in the network of these channels that the proposed activities should find their place in the ergotherapy workshop and their application should permit the readaptation to everyday actions in a progressive way.


Radiographic appearance of mycoplasmal pneumonai. As there are contradictory opinions on the radiographic appearance of mycoplasma pneumonai, the chest examination of 59 patients with at least a fourfold increase of the complement fixation titer were studied retrospectively. The investigation shows that there is a great variety of radiologic patterns from interstitial, disseminated infiltrates to total lobar consolidation. The alveolar pattern seems to be more common in women, but there is no relation to age, duration, season or bacterial superinfection. A development from interstitial infiltrates to alveolar changes or vice versa during the course of the illness was not confirmed in this study. The radiographic variability may be explained by the alveolar infiltrates being an inflammatory reaction to Mycoplasma pneumoniae, and the interstitial densities being an immunologic response. No definite difference between bacterial and mycoplasmal pneumonias was observed, but a multitude of alveolar infiltrates speaks for a mycoplasmal origin.


Radiographic patterns of pulmonary involvement in acute mycoplasmal infections. The radiological appearances and the progress of the pulmonary manifestations of serologically-proven acute Mycoplasma pneumoniae infection were studied in 29 patients. The radiological changes seen at and after admission were not helpful in establishing an aetiological diagnosis except in three patients, in whom a "classical" pattern of mycoplasma pneumonia, based on the radiological appearnaces at different histopathological stages of the disease, could be recognised retrospectively. The patterns seen were varied and generally non-specific, and were not related to the age of the patient or to the duration of disease prior to admission. Specific anti-mycoplasma therapy may have prevented the progress of the disease after admission, although five of six patients in whom radiological deterioration occurred after admission were receiving such treatment.


Acute phase of sarcoidosis with splenomegaly and hypercalcemia. Description of a case, including a report about splenectomy and the preparation and testing of a Kveim antigen from the spleen. A young man had a mild, slightly progressive pulmonary sarcoidosis. After 4 years he developed an acute disease with splenomegaly, anemia, marked elevation of ESR, hypercalcemia and mild renal insufficiency. The anemia and ESR elevation disappeared after splenectomy, whereas the hypercalcemia still needs corticosteroid treatment. Attempts to withdraw this treatment resulted in recurrence of the hypercalcemia, but no other abnormalities. In contrast to other organs examined, the sarcoid tissue in the spleen revealed necrosis formation, consistent with a recent process. A Kveim antigen preparation from the spleen was less potent than antigen from mediastinal lymph nodes. It is suggested that the acute phase of the disease involved mainly the spleen. Speculations about the possible role of infectious agent(s) are put forward.


Fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A in pleural effusions. High turnover of fibrinogen in pleurisy. Fibrinogen, fibrin(ogen) degradation products (FDP) and fibrinopeptide A (FPA) were analysed in pleural fluids from 20 consecutive patients with major effusions of various aetiology. FPA is a short-lived polypeptide which is split off from fibrinogen, whereafter fibrin is formed. FDP are formed through lysis of fibrin or fibrinogen. In 18 patients no fibrinogen could be detected in pleural fluid, whereas two (both having malignant tumours) had detectable but low concentrations. High FPA concentrations, interpreted as reflecting very recent fibrin formation, were found in all pleural fluids except for one case of empyema and one transudate. Plasma concentrations were low in most cases. The same pattern was found with regard to FDP, i.e. exudates showed high concentrations, whereas plasma concentrations were low. The only patient with a transudate showed absence of fibrinogen and low concentrations of FDP and FPA. We interpret our findings as indicative of a high rate of fibrin formation and degradation in pleural exudates and have not found any differences between various types of pleural exudates. Consequently, the findings may illustrate the close association between the coagulation system and inflammatory reactions which may be common to most pleural diseases.


Rape pollen allergy.

Rape pollen allergy. Rape plants are cultivated in southern and central Sweden. These partly wind pollinated plants have an exceedingly rich blooming period with pollinating times (for rape and turnip rape) from 10 May to 24 June (+/- 1--2 weeks). In a patient material from southern Sweden with bronchial asthma and other allergic manifestations, rape pollen allergy was found to occur quite frequently. In 366 consecutive patients positive intracutaneous skin tests to rape pollen extracts were found in 85 patients (23%). 54 patients with positive i.c. skin tests for rape pollen were provocated: 81% of them had positive provocation tests. Patients with symptoms of hay fever and/or bronchial asthma during the pollinating season in regions where rape and related species are cultivated should be examined for rape pollen allergy with i.c. skin tests or RAST.


[Antibodies against nicotine-like acetylcholine receptors of central nervous system and muscles in epileptics with IgA deficiency]. Anti-muscle nicotinic acetylcholine receptor (nAR) antibodies were sought in epileptic patients without clinical signs of myasthenia gravis. Low titers of such antibodies were found in 3 cases characterized by primary generalized seizures, IgA deficiency and HLA A1 and B8 antigens. These three patients also had anti-brain nAR antibodies. In the serum of one patient with myasthenia gravis, anti-brain nAR antibodies were also detected. The titer was low despite a high titer of anti-muscle nAR antibodies. This may reflect the fact that the immune reaction in the three epileptic patients is primarily directed against the brain nAR.


[Amebiasis--retrospective analysis of 453 cases in the Zürich region]. In a retrospective study 453 cases of amebiasis were analyzed with regard to duration, purpose, and location of the patients' stay abroad. Diarrhea and abdominal complaints were the predominating features of the history, but occasionally constipation was the only symptom. The patients usually had chronic intestinal amebiasis which was intermittently slightly dysenteric, rather than non-dysenteric as defined by the WHO. There were two cases each of ameboma and colonic stricture and three liver abscesses, one of which proved fatal after complicating peritonitis. Therapy with a tissue and a lumenal amebicide proved to be the most efficient combination, with a success rate exceeding 94% in the controlled cases.


[Antiestrogens: a new endocrine treatment possibility in metastasizing breast neoplasms. Experiences of the Swiss Cooperative Cancer Study Group with tamoxifen]. The detection of specific hormone receptors in normal and tumor tissue has brought new insight into the mechanisms of action of hormones and anti-hormones. The Swiss Cooperative Cancer Study Group (SAKK) has evaluated the antitumor effect of the new antiestrogenic substance tamoxifen in metastatic breast cancer. 158 postmenopausal patients treated with 20 mg/d tamoxifen by mouth are evaluable at present time. Complete and good partial remissions were achieved in 39 patients (25%) largely with soft tissue but also lung and bone metastases. Tamoxifen was well tolerated and caused few serious complications such as thrombosis/pulmonary embolism and hypercalcemia. These results confirm already published experience with tamoxifen, which may replace the estrogens as the primary endocrine treatment in postmenopausal mammary carcinoma metastasizing to soft tissues, lung and bone.


[Human radiation leukemogenesis].

[Human radiation leukemogenesis]. Quantitative data obtained from different groups of subjects are in agreement and make it possible to evaluate the risk of leukemia following total body irradiation with doses exceeding 100 rads of X-rays or lower doses of neutrons. Irradiations which are more localized or administered over a longer period of time retain their leukemogenic effect when the total dose exceeds a few hundred rads. The dose-effect relationship appears to be curvilinear and, from the scientific standpoint, linear extrapolation to predict a low dose effect is not justified. Such linear extrapolation is nevertheless legitimate on grounds of radioprotection but should not be used to evaluate the risk of small doses such as those given for radiodiagnostic purposes (doses in the range of one rad), or those received by a population in the vicinity of a nuclear power station (doses in the range of one rad), or those received by a population in the vicinity of a nuclear power station (doses in the range of a millirad). Combined radio-chemotherapy modalities, as used in cancer treatment and particularly for malignant lymphoma, carry a high risk of inducing secondary leukemias. These combined treatment regimens should be limited to cases for which radiotherapy alone would be insufficient.


A new basis for treatment of multiple myeloma. In order to get a better understanding of tumor biology, prognostic factors and approaches to treatment, total body tumor cell number, cell kinetics and drug sensitivity have been studied in a series of patients with multiple myeloma. We found that the presenting tumor mass stage was inversely proportional to survival, but did not predict drug sensitivity. Patients with both a high tumor cell mass and a large proliferative compartment of tumor cells had a particularly poor prognosis. Studies of myeloma stem cells in agar culture showed individual patterns of drug sensitivity with a correlation between in vitro sensitivity to melphalan, adriamycin, and BCNU, with in vivo sensitivity to these same classes of agents. Use of such measurements may permit selection of useful new drugs as well as an individualized basis for treatment of multiple myeloma.


Congenital and acquired defects of neutrophil granulocytes. It is now clear that deficiences of the production rate or function of neutrophilic polymorphonuclear leukocytes can predispose to recurrent pyogenic infections. Well defined examples of such deficiences include congenital and acquired neutropenias, a dysfunction of neutrophil locomotion and a disorder of neutrophil oxygen metabolism, chronic granulomatous disease, in which affected neutrophils fail to kill catalase-positive microorganisms. The study of congenital and acquired defects of neutrophils has contributed greatly to understanding of normal neutrophil function. This understanding is beginning to permit investigators to exert a "molecular attack" on the difficult problems of neutrophil transfusion and preservation.


[Platelet aggregation during various phases of the menstrual cycle and after therapy with ovulation inhibitors]. Collagen-induced platelet aggregation was studied under well defined experimental conditions in female volunteers on the 6th and 20th days of the menstrual cycle. In addition, another group on long-term contraceptives was investigated. The two parameters studied were the maximum amount and velocity of aggregation. In these three groups no significant changes were found in the parameters studied, and influences of the menstrual cycle and contraceptives on platelet aggregation are therefore unlikely.


[Differential diagnosis of primary and secondary erythrocytosis by means of in vitro culture of hematopoietic stem cells]. Peripheral blood precursor cells from all of 12 patients with polycythaemia vera (PV) formed hemoglobinized colonies in vitro without addition os was strictly epo-dependent in 30 normals and 8 patients with erythrocytosis of other origin. By addition of 1 U epo/ml to the cultures, colony formation was increased up to 5-fold in PV. Untreated patients with a short history had the highest numbers of such epo-responsive precursor cells. In 3 patients with concomitant myelofibrosis, erythroid in vitro growth was abundant, but scattered, single colonies could hardly be identified and their hemoglobinization was poor. This picture did not change with addition of epo, and hemoglobinization did not improve. In vitro grown colonies in PV had morphological abnormalities as compared to colonies grown from normal precursor cells: all stages of erythroid differentiation and up to 50% necrotic cells were found within single colonies. Scattered colonies contained an excess of large, immature, vacuolated erythroblasts. It is concluded that these functionaland morphological abnormalities of in-vitro erythropoiesis are a reliable indicator of PV. Further, transition to myelofibrosis is recognized by a characteristic growth pattern with decreased epo-responsiveness.


[Granulocyte substitution in febrile leukemia patients with bone marrow aplasia. 1. Results of a prospective study]. A prospective, randomized study was performed in aplastic, granulocytopenic, infected patients with acute leukemia during induction therapy. 12 patients received antibiotics alone, and 13 received antibiotics plus 1.7-14.7 X 10(10) (MEAN 6.6 X 10(10) granulocytes by 1-5 (mean 2.7) daily transfusions. In 10 of 12 controls the infection resolved and remission was achieved with granulocyte counts greater than 500/mm3 15 +/- 9 days after randomization. In the transfused patients, infection was brought under control in 10 out of 13 and remission was achieved with granulocyte counts greater than 500/mm3 25+/- 11 days after randomization. Only one death due to infection was observed (6 days after randomization, control).


[Disorders in leukocyte function in diabetes mellitus]. A group of diabetic patients have been analyzed with regard to their defense against infection, i.e. chemotaxis, phagocytosis and bacterial killing. All three steps of leukocyte function are deteriorated in diabetes mellitus. However, no definitive statement on defense against infection can at present be made.


[A safe alternative for the diagnosis of pernicious anemia--a contribution to medical economics (proceedings)]. Mucosal biopsies of corpus and antrum were performed in 17 patients with pernicious anemia. In all patients the corpus mucosa showed atrophic gastritis, while in 16 the antrum was normal or showed only superficial gastritis. This combination is conclusive for pernicious anemia. Over 80% of megaloblastic anemias are caused by pernicious anemia. It is therefore proposed that endoscopy and biopsy be performed as the first examination in these patients. In this way the diagnosis is simple, rapid and economical.


[Erythrocyte migration on filterpaper--a simple micromethod for the measurement of erythrocyte filtrability (proceedings)]. A micromethod for measurement of erythrocyte filtrability is described. The time is recorded for the spreading of drops (25 microliter) of an erythrocyte suspension in filter papers which are calibrated with the suspension solution. The spreading time for the erythrocytes in relation to a reference calibration time correlates well with the filtration time of a modified filtration technique according to TEITEL.


[Human erythrocyte galactosyl transferase: importance in blood group biosynthesis and its absence in permanent mixed-field polyagglutinability (proceedings)]. Human erythrocyte membranes contain two different triton-activated galactosyltransferase activities, one of which is specific for ovalbumin and the other for sialic acid free ovine submaxillary mucin. This latter enzyme was absent in membranes obtained from a patient with permanent mixed-field polyagglutinability.


[Thrombocyte migration test as a sensitive tolerance test before platelet substitution (proceedings)]. Thrombocytopenic patients refractory to random-donor platelet support can usually be substituted by platelets obtained from donors identical with respect to HLA-A and -B antigens [1]. Since such "full-house" identity is rarely available, reliable cross-match tests (CM) are needed in order to pick out donors compatible in spite of HLA non-identity. By use of the thrombocyte migration test (TMT), DUQUESNOY et al. have shown that antiplatelet antibodies may exert an inhibitory effect on platelet migration. Therefore, we have explored this test system for its efficiency as CM compared with the "long-time" lymphocyte cytotoxicity test (LLT). Of 8 sera from polysensitized patients, serial dilutions were performed and simultaneously tested by TMT and LLT with cells obtained from the same control individuals. The sensitivity of TMT exceeded LLT by 2-4 dilution steps in all sera tested. Moreover, 9 patients with incompatible transfusion responses to single-donor platelets in spite of negative LLT had the following results in TMT with pre-transfusion sera: 5 positive (i.e. migration inhibition), 1 negative: enhanced migration was observed 3 times. This phenomenon of enhancement remains to be clarified, since low titers of anti-HLA-antibodies do not cause enhanced platelet migration. Repeated transfusion of platelets obtained from the same donor may cause antibody production against leukocytic antigen not shared by platelets, leading to "false-positive" LLT. 2 patients were successfully substituted with platelets from HLA/MLC-identical siblings in spite of positive LLT, but with negative TMT; in 2 cases with unrelated HLA-A and -B identical donors, TMT results were inconsistent.


[Missing thrombinemia in the so-called hypercoagulability following physical exertion (proceedings)]. A common topic of discussion for many years has been whether stress induces hypercoagulability and/or hyperfibrinolysis. Ten healthy volunteers were subjected to strenuous physical effort on a bicycle ergometer. Blood samples were collected 10 min before and immediately after exercise. The well-known activation of blood coagulation was demonstrated by significant shortening of the activated partial thromboplastin time, thrombin and reptilase times. However, no fibrinopeptide A (FPA) was generated, nor did the ethanol gelatin test turn positive. A significant shortening of the euglobulin lysis time was indicative of fibrinolysis but no fibrin(ogen) degradation products (FDP) could be detected. These results show that the so-called hypercoagulability is not accompanied by thrombin-mediated release of fibrinopeptide A, and suggest that the activation of coagulation does not involve fibrinogen to fibrin conversion.


[Thrombin formation in factor IX concentrates and FEIBA (factor eight inhibitor bypassing activity) (proceedings)]. Having observed a marked increase of the fibrinopeptide A (FPA) level in vivo in 5 patients after the administration of factor IX concentrates, 8 factor IX concentrates (IX-K) and one FEIBA (factor eight inhibitor bypassing activity) fraction have been studied in vitro to ascertain whether thrombin was present or could be generated. Using fibrinogen as a substrate, the release of FPA under various conditions was measured by radioimmunoassay and it was found that (1) the addition of CaCl2 to the IX-K was necessary to produce FPA release; (2) the reaction was mainly dependent on the incubation time of the concentrate and the CaCl2 and (3) the release of FPA could be inhibited by heparin. The FEIBA fraction instantly produced FPA with or without the presence of CaCl2. It is therefore questioned whether the main effect of such products is due to a "factor II bypassing activity", i.e. thrombin.


[Immunopathology in a case of kala-azar (proceedings)]. A 33 year old woman was admitted to hospital for fever of unknown origin. Leishmania donovani was found in histological preparations from lymphnodes and by sternal puncture. Circulating immune complexes present in high concentration were isolated and characterized. The circulating immune complexes remained elevated two months after the disappearance of Leishmania from the bone marrow.


[Increase of unsaturated transcobalamine II in autoimmune diseases; effect of immunosuppressive therapy (proceedings)]. Transcobalamin II (TC II) is a serum protein responsible for transporting vitamin B12 to the cells. A previous observation of a child with congenital TC II deficiency and agammaglobulinemia suggested that this protein plays an important role in the immune response. Accordingly, TC II levels ere determined in 32 patients with autoimmune disease (AID) (i.e. 26 with lupus erythematosus, 4 with dermatomyositis, and 2 with autoimmune hemolytic anemia) and in 40 patients with acquired immunodeficiency due to chemotherapy. It was found that elevated TC II levels corresponded to active phases of AID. Changes in TC II levels correlated better with the clinical course of AID than complement, antinuclear antibody or native DNA binding capacity. This suggests that TC II could be a valuable parameter in following up activity of AID.


[Lymphoproliferative diseases with small molecular (monomere) IgM paraproteinemia (proceedings)]. Phytohemagglutinin P, when used like an antiserum in immunoelectrophoresis, precipitates with pentameric IgM but not with monomeric IgM subunits. In a retrospective study this simple screening method was applied to 180 sera containing monoclonal IgM. Five cases were found to be of the monomeric type of IgM paraproteinemia. Four of these patients had lymphoproliferative diseases with lymphocytic infiltration of the bone marrow. The last case was complicated by acute myelomonocytic leukemia.


[Isolation of human tumor cells: conditions for in vitro diagnostic and therapeutic studies (proceedings)]. With a view to the possible use of human tumor cells for diagnostic and therapeutic tests (e.g. determination of hormone receptors, sensitivity to cytotoxic drugs, cytotoxicity tests), an attempt has been made to isolate and cultivate pure human tumor cell populations. 49 malignant effusions from 42 patients formed the starting material. The tumor cell isolation was carried out in three steps: 1. elimination of erythrocytes by density-gradient centrifugation or osmotic lysis with triple distilled water; 2. concentration of tumor cells by lg-sedimentation; 3. elimination of adherent cells by short term cultivation in plastic tissue culture flasks. This procedure yielded 95-98% tumor cells. From these suspensions of purified tumor cells, primary cultures were successfully established by supplementing the tissue culture media with autologous effusion fluid.


Electrostatic effects in proteins.

Electrostatic effects in proteins. Electrostatic effects dominate many aspects of protein behavior. When polypeptide chains fold up, most polar side chains seek the exterior, where they can be solvated. Water bound in the interior has been found between the domains of enzymes of the chymotrypsin family, and between the subunits of hemoglobin and tobacco mosaic virus protein. Assembly of this protein from disk to virus is triggered by electrostatic interactions between neighboring subunits. Lysozyme stabilizes the constellation of charges involved in the transition state of its substrate by both permanent and induced dipoles. All factors that lower the oxygen affinity of hemoglobin act by strengthening the salt bridges that constrain its quaternary deoxy (T) structure. Enzymes of thermophile bacteria owe their extra stability mostly to additional salt bridges. The rate of denaturation of hemoglobins by alkali is determined by the ionization of internal side chains with pK's of about 12.


Decrease of human serum fucosyltransferase as an indicator of successful tumor therapy. Surgical removal of colon carcinomas leads to a decrease in the rate of incorporation of [14C]fucose into its endogenous acceptor in human serum; normal incorporation rates are attained within 14 days. A similar time course has been determined for alpha2- and alpha3-fucosyltransferase when either desialo- or desialodegalactofetuin are employed as exogenous acceptors. A correlation has also been seen between transferase activity and the therapeutic response of patients with breast cancer. These results indicate that the determination of fucosyltransferase activity can facilitate the diagnosis of neoplasia, and the success of surgery, chemotherapy, or radiation.


Retention of an associative behavioral change in Hermissenda. The nudibranch mollusk Hermissenda crassicornis is normally attracted to a test light. Three days of training consisting of 50 trials per day of light paired with a rotational stimulus led to a significant increase, lasting for days, in the animal's response latency to enter a test light. The group that received light associated with rotation was significantly different from groups subjected to nonassociative control procedures. Modifications of well-known sensory networks may be related to a behavioral change that shares several operational features with associative learning.


Modification of attention in honey bees. Honey bees were trained in two consecutive two-dimensional (color-position) problems with one dimension (color or position) relevant and the other irrelevant in each problem. As in analogous experiments on dimensional transfer in rats and monkeys, performance in the second problem was more accurate when the relevant and irrelevant dimensions were the same as in the first problem than when they were interchanged. The results of further experiments suggest that the transfer is mediated by different modes of responding that develop in color and position problems rather than by some special process of dimensional selection, such as has been assumed to operate in vertebrates.


Extreme myopia produced by modest change in early visual experience. Chicks whose vision was restricted to the frontal visual field became extremely myopic (mean, -10 diopters; maximum, -24 diopters) and had eyes of increased axial length. Animals restricted to lateral field vision did not differ from normal animals. Monocular deprivation of form vision also produced myopia and eye enlargement and, in addition, produced increased anterior chamber depth.


Ethology of sleep studied with time-lapse photography: postural immobility and sleep-cycle phase in humans. Human sleep is characterized by episodes of immobility punctuated by major postural shifts. The organization of this motor activity was shown with a combination of photographic and electroencephalographic recording to be periodic and related to the electroencephalographic sleep cycle. The amount of immobility as measured photographically was positively related to subjective estimates of the goodness of sleep.


Manufactured hexaparental mice show that adults are derived from three embyronic cells. Two female chimeric mice have been produced by aggregates of three genetically marked eight-cell embryos. All three embryonic genotypes are clearly expressed in the pigment pattern of the adults. These hexaparental mice together with their littermates demonstrate that, in the 64-celled blastocyst, at least three cells, and probably only three, are the source of all adult tissues.


Prevention of death from metastases by immune RNA therapy. The effect of immune RNA treatment on the incidence of death from pulmonary metastases was studied in C57BL/6J mice after excision of a B16 murine melanoma. Immune RNA was extracted from the lymphoid tissues of guinea pigs immunized with B16 tumor and then incubated in vitro with normal C57BL/6J mouse splenocytes. Mice receiving intraperitoneal injections of these RNA-treated syngeneic splenocytes after the primary B16 isograft was resectioned showed significantly improved long-term survival (42 to 67 percent in three successive experiments) as compared to control mice (0 to 20 percent survival) receiving untreated splenocytes. The effect of RNA treatment was tumor-specific and ribonuclease sensitive. The results suggest that immunotherapy with immune RNA may be of benefit to certain patients after surgery for cancer.


Giemsa-11 staining of chromosome 1: a newly described heteromorphism. Sequential Giemsa-11 and C-band staining of the heterochromatic region of chromosome 1 from 30 unrelated individuals revealed a high degree of variability within this region, more than was identifiable with either stain alone. The Giemsa-11 stained material usually appeared as a single band of only slightly varying size within the heterochromatic region. The position of this band ranged from a location immediately adjacent to the centromere, to one farther along the long arm or at the junction of the C-band heterochromatin and euchromatin. Two individuals had a chromosome 1 with no detectable Giemsa-11 band but an average-size C-band. Two others with a large heterochromatic segment by C-banding had two Giemsa-11 positive bands. Additional studies of five members of one family were consistent with transmission of these hetermorphisms in codominant Mendelian fashion.


Induction of ovalbumin synthesis in immature chicks by actinomycin D and thioacetamide. Actinomycin D and thioacetamide induced ovalbumin synthesis and increased serum progesterone concentrations in immature chicks. The increase in progesterone induced by the carcinogens actinomycin D and thioacetamide may account for the induction of ovalbumin synthesis.


Picosecond chemical and biological events. Picosecond spectroscopy is a relatively new field of science that utilizes ultrashort laser pulses to monitor events taking place in the 10(-12) second regime. The continuing development of picosecond spectroscopy has made possible the detection and measurement of the primary events in many physical and tiological processes. This article describes a currently used picosecond spectroscopy system that is capable of reliably recording picosecond events. Two areas of picosecond research are discussed; one concerns the interaction of electrons in fluids, and the second the primary events in vision.


Apparent saturation of blue-sensitive cones occurs at a color-opponent stage. Response saturation of blue-sensitive cone pathways was studied by measuring increment thresholds for violet test flashes on flashed violet fields in the presence of a steady yellow "auxiliary" field of constant radiance. Adding intense yellow field flashes to the violet field flash could eliminate or reduce response saturation (greatly reduce threshold), whereas "negative" yellow field flashes drove the mechanism to further saturation. The response saturation is thus not, in general, controlled exclusively by independent blue-sensitive cones but by spectrally opponent mechanisms that receive opposite-signed signals from blue-sensitive cones and from green-or red-sensitive cones. These results add to a growing number of studies that demonstrate that detection of signals from blue-sensitive cones is largely through a color-opponent pathway.


Physiologically important stabilization of DNA by a prokaryotic histone-like protein. The thermophilic mycoplasma Thermoplasma acidophilum has tightly bound to its DNA a protein that closely resembles the histones of eukaryotes. DNA associated with this protein is more stable than free DNA against thermal denaturation by about 40 degrees C, as shown in both native nucleoprotein and in hybrid nucleoprotein reconstituted in vitro with calf DNA. Since only about 20 percent of the DNA in this organism is associated with the histone-like protein, we suggest that its physiological function is to prevent complete separation of the DNA strands during brief exposures of the organism to denaturing conditions, and thus to facilitate rapid renaturation when normal environmental conditions return.


Lecithin consumption increases acetylcholine concentrations in rat brain and adrenal gland. Consumption of a single meal containing lecithin, the major source of choline occurring naturally in the diet, increased the concentrations of choline and acetylcholine in rat brain and adrenal gland. Hence, the concentration of acetylcholine in the tissues may normally be under direct, short-term nutritional control.


Cocaine plasma concentration: relation to physiological and subjective effects in humans. Volunteer subjects with previous histories of cocaine use were administered cocaine hydrochloride intravenously or intranasally. There was a positive relationship between peak plasma concentration, physiological and subjective responses, and dose administered. The rate of cocaine disappearance after intravenous administration paralleled the drop in physiological and subjective drug effects. After intranasal administration, blood levels remained elevated for a considerably longer period.


Nucleosome arcs and helices.

Nucleosome arcs and helices. Crystals and other regular arrangements of nucleosome cores have been obtained and analyzed in the electron microscope. Two types of regular structures have been studied in detail, the nucleosome arcs and cylinders. The latter are composed of concentric cylindrical layers of intertwined right-handed helices of nucleosome cores. These studies lead to the following conclusions and concepts. The overall structure of the nucleosome core is a short, wedge-shaped cylinder measuring about 110 by 110 by 60 angstroms. Nucleosome cores interact primarily between top and bottom planes. Nucleosome cores exhibit large conformational variability. A pivot allowing two degrees of rotational freedom is postulated in the region of the 70th base pair to account for this property of the nucleosome.


Intraspecific evidence for the function of single and double cones in the teleost retina. Retinal growth in young Sebastes diploproa involves the succession of three distinct cone patterns. Development of the final pattern with the loss of single cones occurs in close temporal association with a permanent migration from the surface to deep water. The results suggest that loss of single cones depends upon the change in environment and that the loss occurs through fusion to double elements.


Prolactin synthesis by human chorion-decidual tissue: a possible source of prolactin in the amniotic fluid. Explants of human chorion-decidual tissue obtained at delivery from normal, full-term pregnancies synthesize and secrete prolactin. This hormone is indistinguishable from pituitary prolactin by chromatographic, electrophoretic, immunologic, and receptor assay techniques. These results suggest that chorion-decidua may be the source of the large quantities of prolactin in amniotic fluid.


The attention operating characteristic: examples from visual search. Even in the absence of eye movements, we show that subjects are able, upon instruction, to selectively attend to certain kinds of targets and parts of visual arrays. The major mechanism of altering attention is the switching of attention from trial to trial, although intermediate states of shared attention do occur. Attention operating characteristics are shown to be a useful way of describing such data and of assessing the compatibility of tasks to be performed simultaneously.


Regulation of macrophage tumoricidal function: a role for prostaglandins of the E series. Exogenously added prostaglandins E1 and E2, but not F2alpha, inhibited the tumoricidal activity of interferon-activated macrophages of mice. A role for adenosine 3',5'-monophosphate (cyclic AMP) in modulating macrophage functional activity was suggested because prostaglandins of the E series increase intracellular concentrations of cyclic AMP in macrophages and because treatment of interferon-activated macrophages with dibutyryl cyclic AMP consistently inhibits expression of cytotoxicity. Since the activated macrophage releases high concentrations of prostaglandin E2, it is postulated that this prostaglandin could act locally in negative feedback inhibition to limit cell activities.


Effects of the home environment on withholding behaviors and conditioning in infant and neonatal rats. Rats 16 days old received passive-avoidance training in the presence or absence of home litter cues. Rats trained in the context of home litter cues learned the passive avoidance reliably faster than rats trained in isolation. In the presence of home litter cues, 16-day-old rats also exhibited more adultlike spontaneous alternation. Pavlovian conditioning of rats trained at 2 days of age was studied in the presence and absence of conspecifics. These experiments suggest that deficiencies in inhibitory behaviors and conditioning associated with immaturity can be alleviated when the testing environment is made more similar to the home environment.


Astigmatism in infants.

Astigmatism in infants. Compared with children of school age, infants show ten times the incidence and considerably greater amounts of clinically significant astigmatism. The amount begins to decrease in the second semester of life, and the incidence declines during the third year. The unanticipated results bear on both the etiology and the neural sequelae of astigmatism.


Infant astigmatism measured by photorefraction. Photorefraction of a sample of 93 infants of ages 1 day to 12 months showed that 63 percent of the subjects had astigmatism of 0.75 diopter or greater, and 12 percent greater than 2 diopters. Seventy percent of these astigmatisms were in the horizontal-vertical meridians. By comparison, only 8 percent of a sample of 26 adults tested by the same method showed astigmatism (all 0.75 to 1 diopter). The high incidence of infant astigmatism has implications for critical periods in human visual development and for infant acuity.


When to investigate and when to treat hypertension. When a raised blood pressure is found, a thorough clinical assessment and a few simple investigations are sufficient in the average patient. There are certain clear indications for treatment, but there is a grey zone where suggestions only can be offered. The importance of follow-up examinations, drug side-effects and associated risk factors is stressed.


The doctor as a humanist.

The doctor as a humanist. The education of the doctor, traditionally based on the classics, is now founded on the sciences. However, the practice of medicine on individual patients will remain an art. The problems of delivery of health care in the next millenium will be moral and ethical rather than scientific. A broad, liberal, humanistic education will be required.


A survey of admissions and deaths in a black paediatric department. Patterns of paediatric illness in hospital were surveyed with a view to planning for improved community health services. High morbidity and early mortality from neonatal, nutritional, gastro-intestinal and respiratory disease reflected late referral to hospital of seriously ill children. Combined preventive, promotive and primary care clinics, health education and improved transport facilities for the sick are a high priority for the area.


The midwife obstetric unit.

The midwife obstetric unit. The urgent need for an alternative to domiciliary delivery in Cape Town has been met by the development of midwife obstetric units (MOUs). These units are situated in suburbs with a high population density. They are staffed entirely by midwives and are linked by telephone to the base hospital. A flying squad service is available at the regional centre (the maternity block at Groote Schuur Hospital). Regular visits are made to the units by the medical staff. Strict criteria for delivery at the MOUs have resulted in a very low perinatal mortality rate, and the units have at the same time relieved the serious overcrowding in the teaching hospitals. The concept of the MOU is particularly suited to Africa and indeed to any developing country.


Increased erythrocytic diphosphoglycerate in megaloblastic anaemia. A compensatory mechanism? The levels of erythrocytic 2,3-diphosphoglyceric acid (2,3-DPG) in a group of patients with megaloblastic anaemia were compared with levels in an iron-deficient subject. The megaloblastic cells appeared to have 2 mumol more 2,3-DPG per g Hb than the iron-deficient cells, at the average haemoglobin level found in the megaloblastic group. The anticipated adaptive decrease in the oxygen affinity of the blood was not apparent when the relationship of P50 (7,4) to haemoglobin level was examined. This was shown to be due to a decreased mean corpuscular haemoglobin concentration (MCHC), which counteracted the effect of the increased 2,3-DPG.


The clinical and histological features of South West African cutaneous leishmaniasis. The clinical and histological features of 18 cases of dermal leishmaniasis encountered in South West Africa are described and discussed. The anatomical distribution of the leishmanial lesions differs from that encountered elsewhere in Africa, but the histopathological changes follow a pattern similar to that of Oriental sore in other parts of the world.


Cutaneous leishmaniasis in Southern Africa. A case report. The microscopical findings in a case of cutaneous leishmaniasis from South West Africa are presented in order to highlight the pathology of this disease and facilitate its recognition, should unsuspected cases occur in the Republic of South Africa. In addition, the ultrastructural findings confirm the presence of typical Leishmania which occur in the cytoplasm of macrophages where they are undergoing destruction. This adds a further dimension to the characterization of this disease in southern Africa.


Cystinosis with Fanconi's syndrome. A case report. A 19-year-old girl suffering from the nephropathic form of cystinosis presented with the full clinical and biochemical picture of Fanconi's syndrome. Polyuria, polydipsia and photophobia associated with severe growth retardation and rickets were the main clinical features. The essential biochemical abnormalities consisted of hypophosphataemia, hypokalaemia and hypo-uricaemia together with a systemic acidosis and a reduced creatinine clearance rate. There was generalized amino-aciduria, glycosuria and bicarbonaturia. In addition, the fractional excretion of potassium, phosphate and uric acid was significantly increased. Slit-lamp examination of the cornea and histological examination of the conjuctiva, liver, bone marrow and kidney demonstrated cystine crystals.


Infective endocarditis complicating congenital heart disease. The pathological alterations in 34 patients with infective endocarditis complicating congenital heart defects were studied. The overall incidence of infective endocarditis in patients with major congenital cardiac defects was 4,7%. Most patients were under 31 years of age and males predominated. The infection was associated with Fallot's tetralogy in 10 patients (17%), ventricular septal defect in 7 (4%), bicuspid aortic valve in 7 (16%), coarctation of the aorta in 6 (8%), atrial septal defects in 2 (1%), and patent ductus arteriosus and pulmonary artery branch stenosis in 1 patient each. The causative micro-organisms were successfully cultured from only 29% of patients. Fourteen of the 34 patients had infection of an associated 'jet' lesion. Patients with isolated ventricular septal defect showed tricuspid valve endocarditis more commonly than did patients with Fallot's tetralogy. The infection had been missed clinically in 34,8% of patients, 50% of whom were aged 3 years or younger.


Serum calcium, magnesium, phosphorus, alkaline phosphatase and 25-hydroxyvitamin D concentrations in children. Serum calcium, magnesium, phosphorus, alkaline phosphatase and 25-hydroxyvitamin D concentrations for Coloured children between the ages of 1 and 17 years are reported. No evidence of vitamin D deficiency was found. The problem of the interpretation of 'normal' alkaline phosphatase concentrations is highlighted.


The impact of renal failure on the South African black and his attitude towards haemodialysis. Four years' experience with haemodialysis in South African Blacks has afforded an insight into their beliefs and superstitions about kidney function and kidney disease, the role of the extended family and the influence of traditional healers on the pattern of management of patients with chronic renal failure. Despite a vastly different cultural background and basic ignorance of biology, their reactions and adaptations to maintenance haemodialysis are closely similar to those reported from modern Western societies.


Endogenous and exogenous heptadecapeptide gastrin transport across the pig liver. In vivo studies in the pig showed no net loss or gain of endogenous porcine gastrin during transport across the liver in fasting animals. Infusion of synthetic human heptadecapeptide gastrin (G-17) in doses of 0,25, 0,5 and 1,0 microgram/kg/min raised circulating gastrin levels to those found in the postprandial state. At no time was there a loss or gain of immunologically determined gastrin across the liver. Changes in the molecular size of gastrin, however, suggested that qualitative but not quantitative effects followed the administration of G-17 in vivo. The disappearance of gastrin from the circulation was biphasic, with an initial half-life of 3 minutes and a slower phase suggesting recirculation or multicompartment equilibration. The distribution at equilibrium was +/- 20% of body weight calculated from arterial levels, but 30-40% if portal or hepatic venous values were used. The mean blood production rate was +/- 125 microgram/day but the portal contribution was only 30 microgram/day, suggesting an important alternative source of gastrin.


Infantile apnoea due to profound hypocalcaemia associated with vitamin D deficiency. A case report. In this report a 7-week-old infant with stage 1 rickets, profound hypocalcaemia and recurrent apnoea is described. The patient responded initially to calcium supplementation, and subsequently to therapy with vitamin D.


Electrocardiographic and biochemical studies on marathon runners. The electrocardiographic findings and certain biochemical observations in 48 male runners before and after participation in the Comrades Marathon race are presented. In 21 of the 48 runners electrocardiographic changes consistent with early ischaemic heart disease could be demonstrated before the race. In 2 runners who had normal tracings before the race, abnormalities could be shown after the race. The total serum creatine kinase activity was markedly elevated after the race in the majority of the 23 runners in whom this was measured. In 11 of these subjects, the Marsh-Bender (MB) fraction could be demonstrated after the race. It is concluded that an elevated MB fraction is probably not a reliable index of myocardial damage after strenuous exercise.


The diagnosis and management of diverticular disease. Diverticular disease is very common among elderly members of "Western, civilized" communities. The aetiopathogenesis is unknown, but may be related to diet and raised intracolonic pressure. Patients with diverticulosis are usually asymptomatic, but those with diverticulitis (which implies inflammation) often present with pain, pyrexia and changes in bowel habit. Careful differential diagnosis is necessary to permit appropriate treatment (medical or surgical), and to detect and treat potentially dangerous complications (abscess, peritonitis, haemorrhage, stenosis, fistula).


Ligamentous injury of the cervical spine--two radiological signs. The integrity of the posterior ligamentous complex is important for the stability of the cervical spine. Severe ligamentous injury may occur without radiological evidence of vertebral fracture or dislocation. If overlooked, ligamentous damage may result in vertebral instability with subsequent dislocation and spinal cord injury. Two radiological signs, acute kyphotic angulation and divergence of the spinous processes, which are indirect evidence of ligamentous damage, are described.


The changing role of doctors in the Soweto clinics' health care teams. Delegation of common health problems and their management to specially trained primary health care nurses allows the clinic doctor in a health care team to employ his own skills and time more effectively. He may become an expert in comprehensive community health care or develop related research interests, and thus help to promote optimal health services relevant to the local situation.


[Malignant hyperthermia in a black child. A case report]. A case of malignant hyperthermia in a Black boy is presented. He developed this condition during repair of a cleft palate, with halothane as the triggering agent. The importance of the high incidence of malignant hyperthermia in patients with certain musculoskeletal abnormalities is stressed. Despite a cool and well air-conditioned theatre, the patient's temperature was 41 degree C when the condition was suspected. At that stage general muscle rigidity was present. The patient was successfully treated with procainamide, sodium bicarbonate and hydrocortisone; surface cooling (with ice packs) was instituted and the stomach was washed out with ice-cold Ringer's solution. Over a period of 14 days serum creatine phosphokinase values decreased from 630 IU (on the day of the incident) to 12 IU. A muscle biopsy showed variation in muscle fibre size. Electron microscopical studies showed myofibrillar disruption and folding of the basement membrane. A modified version of Denborough's technique was used for the in vitro exposure of muscle strips to halothane and suxamethonium. Isometric contraction was measured and recorded. A severe contraction followed the exposure of muscle strips to halothane, which confirmed the diagnosis.


Maternal intensive care.

Maternal intensive care. The evolution of a maternal intensive care unit (ICU) is described and the management of the patients treated over a 10-month period is outlined. The principles, practice and methods of intensive care for the parturient are discussed.


Efficacy and acceptability of injectable medroxyprogesterone. A comparison of 3-monthly and 6-monthly regimens. Five hundred Black Rhodesian women given injections of 150 mg Depo-Provera every 3 months (group A) and 500 women given an injection of 450 mg Depo-Provera every 6 months (group B) were reviewed after 6 months. Group B had a significantly lower rate of defaulters. There was no significant difference between the groups with regard to weight gain, systolic and diastolic blood pressure increase, overall abnormal bleeding patterns and complaints of side-effects. Among those women who reported abnormal bleeding patterns, significantly more in group B had amenorrhoea. There was no significant increase of prolonged bleeding in group B. Among those women who complained of side-effects, significantly more in group B complained of headaches and a bloated abdomen. No pregnancies occurred in either group. The increased annual cost of the 450 mg injections, which was the main reason for women not accepting this regimen, is outweighed by convenience and reduced travel costs. Depo-Provera 450 mg given by 6-monthly injection is well tolerated and effective, and appears to be even more satisfactory as regards continued acceptance than 150 mg given every 3 months.


Evaluation of a combined oestrogen-progestogen injectable contraceptive. A combined injection of 50 mg medroxyprogesterone acetate and 10 mg oestradiol cypionate (Cyclo-Provera; Upjohn) was administered monthly for periods ranging from 1 to 18 months, to 120 Black women of reproductive age. No major side-effects were noted, no pregnancies occurred in the 575 cycles studies, and the pattern of regular menstrual bleeding was acceptable. Amenorrhoea occurred in 15,8% of patients but only 2,5% requested a change of treatment. The incidence of amenorrhoea diminished with continued use. This contraceptive regimen appears to be a useful addition to the methods presently available. Certain aspects merit further study.


Intra-uterine extra-amniotic prostaglandin F2-alpha in the management of patients with intra-uterine fetal death. The problems of a conservative approach to the management of patients with intra-uterine fetal death are presented, and the technique of intra-uterine, extra-amniotic infusion of prostaglandin F2-alpha (PGF2alpha) is described. This involves the repeated infusion of a solution of PGF2alpha into the extra-amniotic space to induce labour in patients in whom pregnancy is complicated by intra-uterine fetal death. Pregnancy was successfully terminated by this method in 9 patients with intra-uterine fetal death. The mean induction-delivery interval was 10,2 hours. There were no side-effects, and the results were similar to those reported by other authors who used a similar technique of inducing labour. Past and present methods of inducing labour in patients with intra-uterine fetal death are reviewed and discussed.


An analysis of the first 200 legal abortions at the Johannesburg General Hospital. A retrospective study was made of the first 200 terminations of pregnancy at the Johannesburg General Hospital since the promulgation of the Abortion and Sterilization Act of 1975. The indications for termination of pregnancy, the ages, marital status and parity of the patients, the procedures and their complications are analysed. Psychiatric factors were cited in 76% of cases. Further indications were rubella infection in the first trimester of pregnancy, medical, genetic and legal factors. The use of intra- and extra-amniotic prostaglandin administration is compared.


The Abortion and Sterilization Act in 1975--experience of the Johannesburg Hospital Pregnancy Advisory Clinic. The experience of a Pregnancy Advisory Service operating in terms of the Abortion and Sterilization Act of 1975 is reviewed. A total of 454 applications for abortion were considered, of which 198 (44%) were accepted and the abortions performed. The urgent need for sex education at schools, colleges and universities is stressed, in view of the large number of scholars and students under the age of 17 who seek an abortion. There are also patients who discontinue contraception for a variety of reasons, on medical advice or otherwise, without an alternative being suggested or sought. Motivation of patient, nurse and doctor needs urgent improvement.


The quantitative effect of lumbar analgesia on uterine work output. The effect of lumbar epidural analgesia on uterine work output was studied in 36 women during labour. During the first 10 minutes after administration of the local anaesthetic agents there was a 46% loss of uterine activity. In 72% of patients uterine activity returned to normal within 30 minutes. Seventeen per cent of patients required additional oxytocic stimulation.


Haemodialysis in pregnancy. A case report. A successful outcome of haemodialysis in a pregnant patient with chronic glomerulonephritis is reported. After a stable period of 9 years, pregnancy resulted in a definite deterioration of renal function. The importance of establishing biological maturity in preference to gestational maturity is stressed.


The prevalence of hypertension in the urban Zulu. In a random house-to-house study of 18000 urban Zulus the overall prevalence of essential hypertension was %25 (female 27%; males 23%).  Women between the ages of 35 and 40 years had a higher prevalence than men.  The mean arterial pressure according to age and sex was not as high as in the American Negro, West Indian or Nigerian, but certainly higher than in most Caucasian populations.  The mean arterial pressure rose with age, showing a greater rise in systolic than in diastolic blood pressure.  More effective screening and therapeutic programmes should be initiated in Blacks, since this study showed that 90% of the subjects who had hypertension were undiagnosed, undetected or inadequately treated.


Chronic illness in non-institutionalized persons.  Part II. Who cares? A survey was conducted to evaluate the care being received by non-institutionalized chronically ill persons in the Black, Coloured  and White communities residing in the Municipality of Cape Town. Of the chronically ill persons identified, 170 (71%) of the Blacks, 188 (62%) of the Coloureds and 43 (86%) of the Whites were receiving care at the time of the survey, and the type, location and duration of this care are outlined.  Only 26% of the chronically ill persons were considered to be receiving optimal care, and new recommendations for care were made for 201 (84%) of the Blacks, 203 (67%) of the Coloureds and 36 (72%) of the Whites.  Of the patients for whom new recommendations were made, 37% were not currently receiving any care.  The financial and occupational repercussions of chronic illness are considered, and methods of improving the comprehensive care of chronically ill persons are discussed.


Hypotension after lumbar epidural analgesia. Despite preloading with fluid, a fall in the mean arterial pressure was recorded in 66% of patients after standard epidural analgesia.  In 83% of patients in whom blood pressure fell, hypotension was classified as moderate or severe.  In cases of severe hypotension the dermatome level of the block always surpassed T9. The maximal fall in blood pressure always occurred within the first 25 minutes after administration of the local anaesthetic agent.


Congenital tuberculosis. A report of a probable case. Extensive miliary pulmonary tuberculosis in a 17-day-old infant born to a mother with pulmonary tuberculosis is described.  It was assumed that the patient probably had congental tuberculosis.  We report our findings to draw attention to a rare disease where a high index of suspicion, timely diagnosis and adequate management are essential if treatment is to be successful.


Coronary heart disease diagnosed as cardiomyopathy in blacks. A report of four cases. Four Black South Africans presented with cardiac failure which was diagnosed as being due to cardiomyopathy.  Necropsy examination revealed that all 4 patients had had severe coronary atheroma and myocardial infarction during life.


The high rugby tackle--an avoidable cause of cervical spinal injury? The type and circumstances of injury to 14 rugby players with cervical spinal cord damage sustained during a tackle have been analysed. Two specific mechanisms of injury were evident. Four players were injured when their heads collided with fixed objects while they were attempting to tackle an opponent. Ten players were injured while being tackled and 5 of them were tackled around the neck. The risk of trauma to the cervical spine caused by the force applied to the neck in a high tackle is discussed. The susceptibility of the ligaments of the cervical spine to the rotational force exerted during a high tackle is stressed. An amendment to the rules of rugby, which would reduce cervical trauma, is suggested.


Plasma lipids and hepatic lipid synthesis following portacaval shunt in the rat. End-to-side portacaval shunt (PCS) in the rat exerted an antilipaemic effect which was most marked for esterified cholesterol and triglycerides. In vitro hepatic lipid synthesis did not correlate with serum lipid values and it is unlikely that decreased biosynthesis in the mechanism of the antilipaemic action of PCS in the rat.


The hyperviscosity syndrome in an IgA-2 myeloma patient. We have compared serum viscosities in 2 patients with the IgA type of multiple myeloma. One patient had the rare condition of IgA-2 myeloma. We confirm that hyperviscosity is associated with higher polymers. It would appear that there is no barrier to polymer formation with the IgA-2 subclass.


Biliary ascariasis--endoscopic aspects. Report of 4 cases. Retrograde cholangiography was carried out in 4 small children with suspected roundworm infestation of the biliary tree. An adult-sized side-viewing fibre-optic duodenoscope was employed, and a general anaesthetic was given in each case. Roundworms were frequently seen protruding from the papillary orifice when biliary infestation was present. Cannulation of the duodenal papilla was shown to be eminently feasible in these small children, whose average weight was 12,4 kg. The degree of infestation and the response to vermifuge therapy could be determined with precision by retrograde cholangiography. It is suggested that this procedure has a place in the management of the complicated case of biliary ascariasis, and that it should certainly be considered when surgery is contemplated.


Climate and disease.

Climate and disease. A summary of the literature shows that there are well-marked seasonal variations in mortality for total deaths, for respiratory and cardiovascular diseases and for diabetes, the mortality rate being higher in winter than in summer. These seasonal variations in mortality are seen in infants under 1 year of age and in older people but not in youths and young adults. The amplitude of the seasonal variation in mortality increases with increasing age because of the higher incidence of cardiovascular and respiratory mortality in older people. Seasonal variations in air temperature are a more important determinant of seasonal variations in respiratory and cardiovascular deaths than are fluctuations in air pollution; there is usually a time-lag of up to a week in the change in air temperature before the mortality rate for these diseases increases; a run of 4 - 5 days of stressful temperatures (either hot or cold) has more effect on mortality than an isolated hot or cold day. Examination of the seasonal variations in all causes of death of the four population groups in South Africa shows that Whites and Asians display the typical pattern of a winter high and a summer low mortality of populations in developed countries. The seasonal variation in mortality of Coloureds and Blacks is quite different. It shows two peaks, one in winter and one in summer. This bimodal pattern in the seasonal variation is due to the fact that one-third of all Coloured and Black deaths occur in infants under 1 year of age and most of these deaths occur in summer as a result of gastro-enteritis. Comparison was made of the seasonal variations in mortality rates for all causes of death and for respiratory and ischaemic heart disease (IHD) deaths of Whites over 40 years of age in Durban and Johannesburg. This showed that the seasonal variation for all causes of death is greater in Johannesburg than in Durban, i.e. proportionately more older Whites die during winter in Johannesburg than in Durban. The reason for this difference is that the seasonal variation in respiratory disease mortality is much greater in Johannesburg than it is in Durban, but the seasonal variation in IHD mortality is the same in the two cities.


Percutaneous embolization for post-traumatic renal haemorrhage. Treatment of post-traumatic renal haemorrhage by percutaneous embolization in 9 patients is reported. Successful control of haematuria was achieved in 8 patients and 1 patient was referred for surgery. The arteriographic findings and technique are described. One patient developed hypertension but there were no other complications. Super-selective renal arterial embolism can provide definitive therapy in renal trauma, and major surgery may be avoided in most cases.


The lumbar disc brace.

The lumbar disc brace. An inexpensive, light-weight and cosmetically acceptable brace for the lumbar spine has been submitted to clinical trial over a period of 16 months and has proved effective, both in averting surgery and in facilitating a quick return to duty.


Is the witchdoctor medically competent?

Is the witchdoctor medically competent? Any possible collaboration with indigenous healers presupposes a precise knowledge of what they do. Diviners are specialists in social relations and their expertise can be of benefit to medical practice. The medicines employed by herbalists are not usually therapeutic in the physical sense. They operate on a mystical and symbolic plane, which is foreign to the practice of "Western" medicine.


Adenoid cystic carcinoma of the uterine cervix. A report of two cases. Two new cases of adenoid cystic carcinoma of the uterine cervix are presented. The first patient, a 45-year-old woman, died from probable pulmonary metastases 1 year after presentation. The second, a 73-year-old woman, was alive, without evidence of disease, 6 months after presentation. Review of the literature and assessment of these 2 cases suggest that this tumour is radiosensitive, and the therapy advocated is radiotherapy followed by wide local excision.


Acral lentiginous melanoma or Hutchinson's melanotic freckle of the extremities. A case report. An additional category of malignant melanoma of the skin, i.e. acral lentiginous melanoma, has been proposed by some authors. The lesion occurs on the extremities, particularly the soles of the feet, the palms of the hands and the digits, but otherwise has the clinical, histological and prognostic features of Hutchinson's melanotic freckle with melanoma. A case conforming to the description of Hutchinson's melanotic freckle of the sole of the foot occurring in a White patient is described. Reference is also made to previous studies of malignant melanoma of the extremities in Black patients. In 15% of these the histogenetic pattern of Hutchinson's melanotic freckle could be observed in the epidermis, adjacent to the invasive melanoma. This pattern was associated with a very much better prognosis than was the superficial spreading or nodular type. The advisability of introducing a new category of acral lentiginous melanoma is therefore questioned.


Pneumatosis coli secondary to colonic obstruction. A case report. A case of pneumatosis coli of the caecum and ascending colon with a closed loop obstruction secondary to carcinoma of the descending colon is presented. The caecum was grossly distended and impending rupture was diagnosed. It is postulated that complete transmural rupture of the caecum was prevented by partial decompression of caecal air into the bowel wall.


Isolated gastric varices -- a separate entity. Report of two cases. Gastric varices may develop in the absence of oesophageal varices and in the absence of portal hypertension. Isolated gastric varices have only recently emerged as a separate entity. The condition is usually due to underlying pancreatic lesions. The diagnosis is made on endoscopy. Bleeding from the varices is best controlled by splenectomy, while the pancreatic lesion is dealt with on its own merits. Two cases are described to draw attention to this condition, and the salient features of this condition are summarized diagrammatically.


Carcinoma in situ in two wives of the same husband. A case report. Two cases of carcinoma in situ in 2 wives (aged 25 and 27 years) of the same husband are reported, and attention is drawn to the high-risk male in the aetiology of carcinoma of the cervix.


The prevalence of hypertension in the Indian population of Durban. In a random house-to-house study of 1 000 Indians the prevalence of essential hypertension according to the World Health Organization (WHO) criteria was 19% (females 22%; males 15%). The study revealed that the prevalence of hypertension was higher than in published data from India. Ethnicity in our study caused a significant variation in prevalence. Prevalence was lower than in our urban Zulu study. Blood pressure rose with age, but there was a greater rise in systolic than in diastolic blood pressure. Prevalence in males and females under 40 years were equal. There was an association between hypertension and diabetes mellitus. More effective screening and therapeutic programmes should be initiated in the Indian population because of the high prevalence of hypertension which may lead to complications if untreated, and because 58% of the hypertensive subjects were untreated or had discontinued therapy.


Correlation of the site of obstruction with the lesion by fine-needle percutaneous cholangiography. The use of fine-needle percutaneous transhepatic cholangiography is becoming a standard procedure for investigating jaundiced patients undergoing surgery. The results of this procedure in 40 patients investigated at the Johannesburg Hospital show the importance of correlating the site of obstruction with the nature of the lesion.


Chondrodysplasia punctata. Report of parent-to-child transmission. A family with chondrodysplasia punctata of the Conradi-Hünermann type is presented. The diagnosis was not made on the affected child who died after orthopaedic surgery for the complications of the condition. The mother had undoubted stigmata of the disease, and a previous child, who died shortly after birth, might also have had the condition. Sound genetic counselling could only be offered after accurate diagnosis was made.


The first 100 patients in the Valkenberg Psychogeriatric Assessment Unit. The Psychogeriatric Assessment Unit is a new development for the care of the psychiatrically ill geriatric patient. An analysis of the first 100 patients admitted to such a unit at Valkenberg Hospital, Cape Town, shows that the investigation and treatment of behavioural and psychiatric disturbances can be effectively done there. The unit is economical as regards staff and their time and achieves really surprising improvement for the majority of geriatric patients who would otherwise have had to be hospitalized for long periods or inadequately cared for by the community. Over 50% of the patients were suffering from depressive illnesses, many of which were associated with physical illness and isolation, and their response to therapy was excellent. The frequent concurrence of physical illness (in 20% of cases admission was for psychiatric symptoms) with rapid improvement after adequate medical treatment was noteworthy. It is essential to have a close association between physician and general medical services. The other finding worth commenting on is that 9 patients were admitted for confusion; in 7 of them this was due to drugs prescribed by medical practitioners.


A report of three years' experience of a Balint group in Cape Town. Three years' experience as members of a group composed predominantly of general practitioners, and constituted to discuss psychological problems encountered in general practice, is reported. Without exception, present and past members found the experience valuable, and particular mention was made of members' increased insight into their own reactions in the doctor-patient relationship. It is hoped that the experience of this group will encourage general practitioners in other centres which do not already have such a group to consider forming similar groups.


Sudden quadriparesis in a patient with rheumatoid arthritis. A case report. A case of sudden quadriparesis in a patient with rheumatoid arthritis is described. The aetiology of motor weakness in the rheumatoid patient is outlined. The natural history of the subluxated rheumatoid cervical spine is once again emphasized.


The rarity of coronary heart disease in South African blacks. Coronary heart disease (CHD) remains an uncommon disorder in the South African Black population. It has been suggested that herein lies an enigma, since it is believed that these people are considerably exposed to the conventional risk factors for CHD. To test this belief I have assessed the exposure of Black people, in time and degree, to the following CHD risk factors: affluence, age, hypertension, hyperlipidaemia, dietary excess, smoking, physical inactivity, diabetes, obesity, hyperuricaemia and hyperinsulinism. Among males only hypertension, and among females only hypertension and obesity, emerged as prominent factors. However, neither of these is significantly atherogenic in the social, nutritional and metabolic milieu in which Blacks generally live, and obesity is a doubtful atherogenic factor, even in westernized populations. It is therefore concluded that the rarity of CHD in Blacks is not enigmatic, but is appropriate to their environmental circumstances.


Circulating antibodies in diabetics treated with conventional and purified insulins. Conventional insulins contain impurities which are immunogenic; these include pancreatic polypeptide (PP), glucagon and somatostatin and intermediates of insulin synthesis co-extracted during purification. Monocomponent (MC) insulins are free of these contaminants. In 49 insulin-treated diabetic patients, antibodies were found to insulin (94%), pro-insulin (68%) and PP (68%). Antibodies to glucagon and somatostatin were not detected. There was a significantly lower mean maximum binding and titre of insulin and PP antibodies and total circulating insulin (i.e. antibody bound and free) in patients receiving MC insulin. In patients treated with MC insulins for longer than 2 years there was a significant fall in the mean maximum binding of insulin and total serum insulin, but no consistent change in diabetes control and daily insulin dose. It seems that except in the special instances of fat atrophy, insulin allergy and certain cases of insulin resistance, there is no need to resort to MC insulin.


The role of the doctor in the changing health service. During the last quarter of a century there has been a gradual change in the doctor's role from that of being the personal provider of medical care to that of the leader of a health care team which is placing increasing emphasis on promotive and preventive health. For the doctor this has necessitated learning additional skills, particularly in the delegation of specific tasks to nurses and other paramedical personnel, the co-ordination of the activities of the health care team, and in teaching and management. The new Health Act of 1977 will enable doctors to develop along these new lines by making closer liaison between hospital and community-based services possible. These new trends in medical care will in turn require urgent re-orientation in planning for new buildings and facilities in the health service; especially with a view to keeping expenditure within available resources so that health skills and knowledge can be made available to everyone.


Severe aortic incompetence caused by systemic lupus erythematosus. A case report. A patient with a 3-year history of serologically confirmed articular systemic lupus erythematosus (SLE), who developed uncontrolled heart failure due to aortic incompetence and who was successfully treated by aortic valve replacement, is described.


Observations on the localization of Absidia corymbifera in vivo. The role of spore distribution and the presence of tissue-specific fungal growth stimulants and inhibitors in determining the in vivo localization of Absidia corymbifera were examined in experimentally infected mice. Intravenous inoculation resulted in generalized distribution of spores, with the highest concentrations accumulating in the liver and spleen. Active lesions containing developing mycelium were confined to the brain, kidneys and occasionally the myocardium. Fungal growth stimulating activity was present in all tissue examined, the liver and spleen being the most active. However at concentrations approaching those of whole tissues, the stimulatory activity of liver and spleen extracts drastically declined whereas that of brain and kidney preparations continued to increase. These effects, in conjunction with local variations in immune processes, were probably responsible for determining the distribution of A. corymbifera mycelial development in vivo.


Immune responses in paracoccidioidomycosis. A controlled study of 16 patients before and after treatment. Serum electrophoresis patterns and various measures of specific and non-specific immune competence were determined in 16 patients with paracoccidioidomycosis, at time of diagnosis and 6 months after therapy. The results were compared with those furnished by the study of 16 control subjects, matched by age and sex. Once treated, the patients approached normality in some parameters. Untreated patients had significantly diminished albumin levels with increased alpha 1, alpha 2 and gamma fractions. Immune gamma globulin G (IgG) was elevated and remained so during therapy. Both before and after treatment patients had diminished total numbers and decreased percentages of E rosettes; they also had depressed lymphocyte transformation with phytohemagglutinin (PHA) and paracoccidioidin (P). Also, untreated patients exhibited the lowest skin test responses to PHA, purified protein derivative (PPD), P and candidin (C); significant differences, however, were limited to the former 2 antigens. All untreated patients had detectable antibody titers against P. brasiliensis; these titers had a tendency to drop during treatment. No direct correlation was found between elevated serum fractions, presence of antibodies and depressed cellular immunity.


A simple low-cost restrainer for the intravenous injection of mice. A plastic syringe has been modified to hold a mouse. The protruding tail is placed in hot water which causes the veins to dilate. The syringe is then clamped to a stand and injection of the vein is easy.


Purine reutilization and synthesis de novo in long-term human lymphocyte cell lines deficient in adenine phosphoribosyltransferase activity. Clonal lines, with either partial or total deficiency of adenine phosphoribosyltransferase (APRT) were derived from the WI-L2 long-term human lymphocyte line by selection for resistance to the adenine analogs 8-azaadenine or 2,6-diaminopurine. Resistance to 8-azaadenine also conferred resistance to 2,6 diaminopurine and vice versa. Cells with 30--40% of wild-type APRT activity were selected by resistance to 0.01 mM 2,6-diaminopurine or 1.40 mM 8-azaadenine. The APRT in the 8-azaadinine-resistant cells exhibited a four- to sevenfold increase in the apparent Km for adenine. Activities of three other purine reutilization and interconversion enzymes in the resistant cells, including hypoxanthine phosphoribosyltransferase (HPRT), adenosine kinase, and adenosine deaminase, were within the range of wild-type activities. The doubling times of the APRT-deficient cells in purine-free medium was not different from wild-type cells. The APRT in the 8-azaadenine-resistant cells did not have an altered mobility in glycerol gradients as compared to wild-type cells. The rate of purine synthesis de novo and intracellular levels of 5-phosphoribosyl-1-pyrophosphate were unchanged in the APRT-deficient cells as compared to WI-L2. The ability of the cells to reutilize exogenous adenine, however, was severely impaired.


Evidence for a striking increase in acetylcholinesterase activity in cultured human fibroblasts which are trisomic for chromosome two. Acetylcholinesterase (AchE) is reported to have a narrowly restricted distribution among human tissues. Three strains of human fibroblasts which are trisomic for chromosome 2 had an average level of AchE activity over 28 times higher than the average level in 19 control strains of human fibroblasts. In contrast, the mean pseudocholinesterase activity of the trisomy-2 strains did not differ appreciably, or significantly, from the mean for the control strains. The 19 control strains included 10 strains trisomic for autosomes other than 2, and 9 euploid strains. Our estimate of the mean AchE activity in the control strains did not differ significantly from zero and might, in any case, have originated from a minute amount of activity contributed to the cells by an esterase in our culture medium. Despite the striking elevation of AchE activity in fibroblasts trisomic for chromosome 2, extracts of these cells had only about 1.5% of the specific AchE activity (per microgram DNA) present in extracts of human cerebral cortex. None of the 22 strains studied had detectable activity for two other enzymes which, like AchE, have a restricted distribution among human tissues: xanthine oxidase and choline acetyltransferase.


Mutations in the structural genes of CHO cell histidyl-, valyl-, and leucyl-tRNA synthetases. Forty-three temperature-sensitive mutants were isolated in the CHO cell line by selecting for noncycling cells using [3H]TdR and cytosine arabinoside. Cell division was extremely temperature sensitive in eight of the mutants, and these were studied in more detail. In seven of these eight mutants, the in vitro specific activity of a single aminoacyl-tRNA synthetase was greatly reduced; four had reduced levels of histidyl-tRNA synthetase, two of valyl-tRNA synthetase, and one of leucyl-tRNA synthetase. Cell hybridization studies showed that the mutants formed three complementation groups. In six of the seven mutants the aminoacyl-tRNA synthetase which had reduced activity was also more thermolabile than the wild-type enzyme. The spontaneous reversion frequency was low for these mutants, and in most cases could be increased by treatment with a chemical mutagen. The isolation of the valyl-tRNA synthetase mutant reported here brings to eight the number of different aminoacyl-tRNA synthetase mutants isolated in the CHO cell line.


Analysis of a method for selecting temperature-sensitive mutants of BHK cells. A procedure for the isolation of temperature sensitive mutants of BHK cells is described. Mutagenized cells were synchronized in G1 by serum starvation at 33 degrees, and, following release, shifted to 37.5 degrees in the presence of FUdR, to kill cells entering the DNA synthetic phase. Eight independently mutagenized series of cells were carried through four cycles of this selection, and surviving cells were tested for ability to grow at 33 degrees and 39.5 degrees after each cycle. The results suggest that such procedure is effective in enriching for non-leaky ts mutants and favors the isolation of mutants which at 39.5 degrees are inhibited in the processes necessary for DNA synthesis and lose viability rapidly. The effectiveness of repeated selection cycles and the general characteristics of the ts mutants isolated by this method were also evaluated.


Genetic and biochemical characterization of mutants of CHO cells resistant to the protein synthesis inhibitor trichodermin. Mutants resistant to the protein synthesis inhibitor trichodermin have been selected in Chinese hamster ovary (CHO) cells. The mutants vary in their stability from those which rapidly lose their resistance to others which are relatively stable after prolonged growth in nonselective medium. Protein synthesis in extracts from the latter class of mutants (Trir) is resistant to the inhibitory action of trichodermin as compared to similar extracts from wild-type cells. After dissociation into subunits, the ability of the 60S ribosomal subunits from Trir cells to function in a protein-synthesizing system is greatly diminished. This subunit also shows reduced binding of [acetyl-14C]TRICHODERMIN. The lesion in Trir mutants therefore seems to have affected this ribosomal subunit. Trir X Tris hybrids are sensitive to trichodermin indicating that the Trir mutation behaves recessively to Tris in hybrids. The Emtr and Trir markers segregate independently from hybrid cells showing that the Trir mutation is probably not linked to the Emtr locus, which as we have shown earlier affects the 40S ribosomal subunit.


Genetic analysis of tumorigenesis: I. Expression of tumor-forming ability in hamster hybrid cell lines. Two new fibroblasts cell lines from a male Chinese hamster embryo are described: one tumorigenic in nude mice (CHEF 16-2) and the other not (CHEF 18-1). Both lines have a stable diploid mode and mean of 22 with 10 pairs of homologous autosomes. The cell lines differ unambiguously in cloning ability in methylcellulose, colony morphology, and tumorigenicity; the expression of these traits was examined in a set of 18-1 X 16-2 hybrid clones. The results show initial suppression of tumorigenicity and anchorage independence, followed by growth in the nude mouse of subsets of cells with chromosomes reduced to the diploid range. Further studies are in progress to establish whether ability to grow in methylcellulose and in the nude mouse segregate coordinately at the cellular level, and whether this segregation has an identifiable chromosomal basis.


Isolation and characterization of L-cell variants with altered sensitivity to glucocorticoids. Stable glucocorticoid-resistant receptor-containing (R+) variants of L cells have been obtained and characterized. Five clones of such cells were obtained after chemical mutagenesis of the A9HT cell line. These clones and an additional, spontaneously resistant subclone of the LB82 cell line all contain glucocorticoid receptors which appear normal with regard to quantity, affinity for steroids, and in vivo localization in subcellular compartments. Somatic cell hybrids were formed between two of these R+-resistant clones, a previously isolated R-resistant clone, and three different sensitive L cell parents. In no case was steroid resistance dominant. Thus, these resistant L cells appear to be candidates for complementation analysis. The R+-resistant clones may be hindered in as yet undefined steps of glucocorticoid action.


Gene expression in euploid human hybrid cells: ouabain resistance is codominant. Single-step mutations to ouabain resistance have been induced in Lesch-Nyhan diploid fibroblasts carrying a variant G6PD isozyme (OuaR/HGPRT-/G6PDA). Two of these mutant strains, differing in the degree of ouabain resistance, were fused with wild-type human diploid fibroblasts (OuaS/HGPRT+/G6PDB) and hybrids isolated in doubly selective medium, ouabain + HAT (HOT). Four hybrids, identified by G6PD heteropolymers and stable tetraploid karyotypes, expressed ouabain resistance intermediate to that of the parents. The degree of ouabain resistance was influenced by the specific mutant allele of the OuaR parent, indicating both mutant and wild-type alleles are simultaneously expressed in hybrid cells. Intraspecific hybrids of this kind are especially suited to studies of gene regulation because all relevant genes present and the number of alleles at each locus is known.


Effect of intercellular communication on the selection of intraspecific human hybrids in HAT and ouabain. Optimal conditions have been determined for selection of hybrids in HAT and ouabain (HOT) from the PEG-mediated fusion of OUAR/HGPRT-/G6PDA and OUAS/HGPRT+/G6PDB human diploid fibroblasts. In addition to the OUARHGPRT+G6PDAB tetraploid hybrids, several other types of HOT-resistant colonies were obtained from these fusions and identified by G6PD isozyme analysis and karyotyping as (1) hybrids contaminated with diploid parental cells, (2) symbiotic mixtures of the two types of parental cells, or (3) spontaneous OUAR mutants. The mechanism for parental cell growth in HOT is most likely the transfer of HAT resistance and/or ouabain resistance through gap junctions formed between resistant and sensitive cells.


Diphtheria-toxin-resistant mutants of CHO cells affected in protein synthesis: a novel phenotype. Stable mutants highly resistant to the protein-synthesis-inhibitor diphtheria toxin have been selected in Chinese hamster ovary (CHO) cells. Protein synthesis in extracts of mutant cells is resistant to the inhibitory action of diphtheria toxin, indicating that the lesion has affected the protein-synthesis machinery. However, about 50% of the elongation factor-2 (EF-2) activity in the mutant cells can still be ADP-ribosylated by diphtheria toxin, and this remaining EF-2 activity is similar to that present in the wild-type cells. We suggest that this result is best explained by assuming that our CHO cells contain two functional copies of the EF-2 gene, and that only one of the copies is altered in the mutants. According to this view, the mutated allele produces EF-2 resistant to ADP-ribosylation which is capable of supporting cell growth in the presence of diphtheria toxin. Although the Dipr marker seems to act dominantly in the parental CHO cells, its behavior in Dipr X Dips hybrids (CHO X CHO) is recessive as measured by cell survival in presence of the toxin. This paradoxical behavior may be due to a gene dosage effect. Segregation studies from hybrids show that the Dipr marker segregates independently of the Emtr and Thgr markers indicating that the Dipr locus is not linked to either the Emtr locus or to the X chromosome.


Biological and biochemical effects of bromodeoxyuridine and deoxycytidine on Syrian hamster melanoma cells. The addition of deoxycytidine (dCyd) to the growth medium of cultured Syrian hamster melanoma cells causes a reversal of the toxic effects of 5-bromodeoxyuridine (BrdU) and a decrease in the extent of incorporation of BrdU into nuclear DNA. These effects of dCyd can be accounted for, in part, by the intracellular conversion of the exogenously supplied dCyd to thymidine (dThd) nucleotides which can compete with BrdU nucleotides for incorporation into DNA. To some extent, the conversion of dCyd to dThd nucleotides can be inhibited by increasing the concentration of BrdU in the growth medium. The conversion of dCyd to dThd nucleotides is inhibited completely by aminopterin (Apt), and Apt also prevents dCyd from reversing BrdU toxicity and from decreasing the level of BrdU incorporation into nuclear DNA. In a clone of Syrian hamster melanoma cells, increasing the concentration of dCyd in the growth medium from 1 micron to 1000 micron resulted in a progressive increase in the percentage of dThd residues in nuclear DNA being derived from the exogenous dCyd, until more than 90% of the dThd residues came from the exogenous dCyd. However, despite the increasing amount of dThd derived from exogenous dCyd, there was a plateau in the decrease in BrdU incorporation into nuclear DNA at concentrations of dCyd above 8 micron.


Detection of lateral asymmetry in the C band of human chromosomes by BrdU-DAPI fluorescence. A lateral asymmetry in the C-band region of human chromosomes is revealed by 4',6-diamidino-2-phenylindole (DAPI) fluorescence in amniotic cells grown for one replication cycle in the presence of 5-bromodeoxyuridine (BrdU). Short-arm segments and satellites of acrocentric chromosomes fluoresce as brightly with quinacrine as the distal part of the long arm of the Y chromosome, and also show a lateral asymmetry. This asymmetry appears to be correlated with highly repetitious DNA, including satellite fractions responsible for C-band staining, and may reflect an unequal distribution of thymine residues between the two polynucleotide chains of the DNA in the C-band region. The C-band region of chromosome 9 fluoresces brightly in both sister chromatids and appears to be symmetrical. This may be the result of multiple inversions in the C-band heterochromatic region.


Isolation of amiloride-resistant clones from dog kidney epithelial cells. The diuretic drug amiloride has been used to select variants from the dog kidney cell line MDCK which are partially resistant to killing by the drug. Evidence is presented suggesting that resistance to killing by amiloride is conferred by decreased uptake of amiloride, which reduces the intracellular drug concentration below the toxic level.