In vitro sensitivity of transplantable leukemias to endogenous granuloid (GCE, GI-2) and lymphoid (T4, T4-1) inhibitors of proliferation. The effect on cell proliferation of crude granulocyte and thymocyte extracts (GCE, T4) and of their target-specific fractions (GI-2, T4-1) was studied in cultures with transplantable subacute myeloid and lymphoid leukemia (ML, LL). In the dose rage studied (1-500 microgram/ml) each factor reduced 3H-TdR incorporation into acid-insoluble DNA of bone marrow, thymus and spleen cells with ML or LL as a function of the dose, approximately linearly. Normal bone marrow proved to be less sensitive to GCE than the ML one: according to parallel line bioassay by a factor of mu = 0.56. The reactivity of LL spleen and thymus is also higher to medium T4-1 concentrations (50-200 microgram/ml) than that of normal lymphoid populations. T4-1 inhibits 3H-TdR incorporation into the DNA of LL spleen cells submaximally in 90': this effect lasts for greater than 7 hours. Because of its more homogeneous cell composition and higher sensitivity, subacute myeloid leukemia is more suitable for screening endogenous granuloid inhibitors than are homologous normal cell cultures.


Antenatal diagnosis: a new dimension in genetic counseling. Antenatal diagnosis has now been accepted as an important aspect of primary care medicine, and counseling patients as to the indications for amniocentesis has become routine. The principal indications are maternal age over 35 years of risk of recurrence of Down syndrome or a neural tube abnormality. Recurrence of sex-linked disorders or of inborn errors of metabolism and presence of balanced chromosomal translocations in parents are less frequent indications. Amniocentesis for cytogenetic analysis and determination of alpha-fetoprotein levels is best performed between 14 and 18 weeks of pregnancy. The scope and limitations of the procedure and its complications should be carefully explained to the parents, as should the risk of the detectable genetic disorder compared with the risk of the diagnostic procedure. On the basis of this information, the parents can make an informed decision for or against amniocentesis.


Clinical cytogenetics: part 1.

Clinical cytogenetics: part 1. This paper is an introduction to the cytogenetic biology of man. It deals with the role of chromosome abnormalities in prenatal death, malformation syndromes, mental retardation, malformation/mental retardation syndromes, abnormalities of sex determination, sex differentiation and sexual function, cancer, and certain genetic disorders in which chromosome abnormalities are seen commonly. Down syndrome is discussed as an important and common example of a malformation/mental retardation syndrome.


Comparison of therapeutic efficacy of doxycycline, chlortetracycline and lincomycin-spectinomycin on E. coli infection of young chickens. Three replicate trials were conducted with broiler male chicks to test the therapeutic efficacy of doxycycline, chlortetracycline and lincomycin-spectinomycin in water against an artifically induced Escherichia coli infection. Mortality, lesion scores (heart, liver and air sac), and performance data were the criteria in evaluating therapeutic efficacy of these drugs. Results indicated the therapeutic efficacy of doxycycline was greater than chlortetracycline and lincomycin-spectinomycin.


Cytoplasmic inheritance of rutamycin resistance in mouse fibroblasts. Mouse fibroblasts resistant to the drug rutamycin were isolated by selectively introducing BrdUrd into the mitochondrial genome of a line of mouse fibroblasts (clone 1 D) lacking a cytoplasmic thymidine kinase enzyme. The ATPase (ATP phosphohydrolase; EC 3.6.1.3) activity of mitochondria isolated from these cells was resistant to rutamycin. The rutamycin-resistant mutants were enucleated with cytochalasin B and fused with mouse A 9 cells resistant to 8-azaguanine and sensitive to rutamycin. Cytoplasmic hybrids, or cybrids, were selected as cells resistant to rutamycin and 8-azaguanine, and appeared at a high frequency. Other fusions between rutamycin-resistant nucleated cells and A 9 produced colonies at a much lower frequency. Finally, fusions between enucleated clone 1 D cells and A 9 cells produced no rutamycin-resistant colonies. These results indicate that rutamycin resistance is a cytoplasmically inherited characteristic in this cell line.


An enzymatic defect in the obese (ob/ob) mouse: loss of thyroid-induced sodium- and potassium-dependent adenosinetriphosphatase. Genetically obese (ob/ob) mice, mice that became obese after treatment with gold thioglucose, and lean animals were studied in the euthyroid state, after induction of hypothyroidism, and after treatment with triiodothyronine. The activity of glycerol 3-phosphate dehydrogenase (sn-glycerol-3-phosphate:(acceptor) oxidoreductase; EC 1.1.99.5] was reduced in the livers from hypothyroid animals and was increased by treatment with triiodothyronine in all groups. The activity of the ouabain-suppressible sodium- and potassium-dependent ATPase (ATP phosphohydrolase; EC 3.6.1.3) was increased by triiodothyronine and reduced by hypothyroidism in the lean and gold thioglucose-treated obese animals. In the obese (ob/ob) mice, on the other hand, treatment with triiodothyronine did not increase the activity of this enzyme, which remained at the level found in hypothyroid animals. This enzymatic activity was reduced in both liver and kidney. Adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] activity in liver membranes, however, was similar in all three groups of mice. This enzyme complex was activated by glucagon and was unaffected by treatment with thyroid hormones. The lack of a thyroid-dependent ouabain-suppressible (Na(+) + K(+))-ATPase in the tissues of the obese (ob/ob) mouse could explain most, if not all, of the abnormalities that have been described in this animal.


Repair of major cranio-orbital defects with an elastomer-coated mesh and autogenous bone paste. We present a method for repairing defects in the craniofacial region in which an elastomer-coated mesh is used as a template with bone paste. The method was developed by animal experimentation first, and then successfully used in the maxillofacial and mandibular regions. We have used this method to repair 16 craniofacial defects with satisfactory results, and complications have been kept to a minimum.


An experimental neurovascular island skin flap for the study of the delay phenomenon. We present an experimental neurovascular island skin flap. It is a consistent, reproducible model which produces a definite pattern of surviving skin flap area versus skin flap necrosis. There is a constant, anatomically definable nerve and vascular supply to the flap. This model permits independent experimental manipulation of the neural, arterial, and venous supply to the skin. It is useful, therefore, for the study of the vascular mechanisms of the skin microcirculation. We also demonstrated that increased flap survival can be produced by a delay involving denervation alone (leaving the vascular supply intact) or by devascularization alone (leaving the nerve supply intact). We conclude that both the adrenergic denervation and the ischemia contribute to the production of the delay phenomenon. We suggest that sustained vasodilation--vascular smooth muscle relaxation--is the vascular mechanism that accounts for the delay phenomenon.


The effects of the perfusion of various solutions on the no-reflow phenomenon in experimental free flaps. The effects of solution perfusion in the free epigastric flap of the rabbit, after normothermic ischemic periods of 8 hours or 12 hours, have been examined by operative microscopic and histological methods. A smaller group of animals was also studied in which the perfusion was done before the ischemic insult. An ischemia-related obstruction to the peripheral blood flow occurred in the absence of stagnant ischemic blood in this model. Although the 3 perfusion fluids studied were shown to penetrate to all levels of a flap after such an ischemic period, none of them had a beneficial effect on skin survival. However, the solution containing mannitol did have a protective effect on fat survival. Analogies between these experimental findings and the clinical situation are made, and the importance of the early diagnosis and treatment of ischemia in a flap is emphasized.


[Osteosynthesis by adherent plates. An experimental physical study]. The creation of ridges of the deep surface of plates used for osteosynthesis increases their adherence to bone. By increasing the coefficient of friction between the plate and the bone, the stresses taken by the screws can be diminished by a third. The procedures diminishes by the same amount the risk of stripping or loosening of screws and thus the risk of pseudarthrosis. Experimental study has been made by measurement with the aid of an elliptometer and modifications in the state of polarization of a Lawer beam under the influence of shearing strains. The strains were those imposed on screws in Araldite fixing a plate whose inferior surface was smooth on one end and ridged on the other. The ridges should not be such as to prevent the later removal of the plate. Screws should be applied for preference with a dynamometric screwdriver because the stress relief is maximal with a tightening force of 12 inch pounds.


[Intertrochanteric osteotomies. A critical study of the clinical radiologic evaluation]. The authors describe the technique that they have used in approximately 500 intertrochanteric osteotomies of the femur. The technique was satisfactory in the production of bony union but in ten per cent of cases there were errors of correction of 5 degrees or more. An analysis of errors related to the radiological technique used showed that a number of conditions (flexion, abduction) modify the angles of inclination and anteversion. A number of instances of degenerative arthritis had been incorrectly attributed to increased coxa valga. An analysis is made of the difficulties encountered when correction is required in two planes, especially when there is fixed flexion or significant anteversion. Some suggestions are made concerning improvements in technique.


[Failures and limitations of the Papineau technic. A report of 54 cases]. The authors have treated 41 cases by Papineau's technique. There were 19 cases of osteitis, and 35 septic non-unions (9 in the femur, 16 in the tibia and 10 in other sites). Twenty-four cases healed, the average follow-up being one year. The causes of failure were analysed. Some are related to the technique itself - sepsis and fractures at the sites of graft removal, inadequate quantities of cancellous bon, long delay in bone union and skin problems particularly in the leg. The indications for this technique are compared with those of other techniques. It is concluded that it is a useful technique; only two patients required amputation.


[Attitude of the paralytic supination of the forearm in children. Surgical treatment in 19 cases]. Nineteen cases of paralytic supination contracture have been surgically treated in children and teenagers. Three successive stages are described - 1) reducible deformity 2) contractures of soft tissues and 3) skeletal deformities. Surgical treatment aimed to improve the patient cosmetically and functionally. Ideally, the condition should be corrected early, during the first stage. The results of the Zancolli procedure of section of the interosseous membrane and rerouteing of the biceps in 11 cases were all satisfactory. Osteotomy of one or both bones could be used in association in cases with fixed deformity.


[Long-distance swimming competitions for the physically handicapped (author's transl)]. Long-distance swimming competitions for the physically handicapped constitute a new measure in sports for the disabled. Such competitions can only be carried out after intensive training as a result of which predictions can be made for sports for the elderly practised for health reasons. Also, younger disabled people with different severely restricted physical functions, e.g., the paraplegics and the thalidomide disabled, are able to take part in these competitions and possibly even to swim against the non-disabled if they are fitted with the appropriate aids. The effects of endurance training are presented on the basis of many years of experiences with a supra-regional swimming group. The possible consequences for leisure time sports in clubs and organisations are discussed. The results and interim times of the two Cologne swimming festivals are documented in detail and analysed to determine performance pre-requisites. The relationship between general sports and sports for the disabled is reviewed and studied in view of a possible social integration.


[Some considerations on sports in workshops for the disabled (author's transl)]. Sports and play can constitute useful components in the production-free programmes of workshops for the disabled. As a result of a survey carried out in 1976 with the help of a questionnaire statements can be made on the sports situation of 150 workshops catering for 19 450 disabled people, i.e., two thirds of the workshop places currently available. Approximately 60% of the disabled do not have the opportunity of participating in sporting activities: 28% have one sports lesson per week, 9% two and 2% three. Table tennis and ball games are the most frequently mentioned. This applies also for the leisure time sports of the disabled. - As there is only a small number of appropriate facilities belonging to the workshops it is recommended that those of neighbouring schools and clubs be used. Sports lessons are usually given by special teachers' assistants with an additional qualification, as there are only a few physical education instructors with a particular knowledge of sports for the disabled. As an interim solution group leaders could be trained as sport supervisors.


[Training of supervisors for sports for the disabled (author's transl)]. There are only a few qualified supervisors for sports for the mentally handicapped although they are greatly needed. The Deutsche Caritasverband (association of German catholic welfare organisations) has now developed a training programme for sports supervisors which follows the training regulations of the Deutsche Sportbund (a German sports association). It is intended for all interested in working with the disabled. The whole training course consists of 180 hours. It is devided into a basic and an advanced course, each lasting one week of 75 study hours. Between these two courses the attendants are obliged to study at home and to observe and work with groups of disabled for at least 30 hours. The studies mainly focus on the two subjects "sports for the physically handicapped" and "sports for the mentally handicapped" and lead to the sports supervisors certificates A or F of the Deutsche Behindertensportverband (a German association for sports for the disabled).


[Priorities of rehabilitation - yesterday, today and tomorrow (author's transl)]. During the last ten years of the Deutsche Vereinigung has made especially important socio-political topics - which are presented in detail in this article - the subjects of its congresses and working conferences. In particular, through the re-organisation of its council the Deutsche Vereinigung has provided the organisations for the disabled, the social security agencies, the representatives of the facilities and the occupational groups a forum for expert's discussions. Today's problems of a restricted number of vocational training places and the structural changes of the labour market have most afflicted the disabled. A solution can only be found within the framework of overall societal considerations which should take into account the question of the possibilities and limits of rationalisation and, in accordance with foreign models, the extension of the special labour market for the disabled. Integration and participation also means involvement in the gross national product.


Studies on the epidemiology of Dictyocaulus filaria infection in Blackface sheep on a low-ground Scottish farm. The excretion of Dictyocaulus filaria larvae in the faeces of Blackface sheep on a heavily stocked lowland farm in south east Scotland, showed considerable individual, week to week and year to year variation. Patent infections were first observed in lambs in May or June but the heaviest and most prevalent infections occurred in the autumn. Infection levels were generally low but infections tended to be prolonged and reinfection occurred following anthelmintic treatment until the late autumn or winter. Only a few very light, short-lived, patent infections were observed in yearlings or adult ewes. Pasture sampling and the use of tracer animals showed that the numbers of infective larvae on the pasture were minimal during the summer months but reached a low peak in the autumn.


The relative susceptibility of Soay and Blackface sheep to natural infection with Dictyocaulus filaria. Simultaneous studies by faecal larval counts on a mixed flock of Blackface and Soay ewes, yearlings and lambs suggested that the Soay animals were less able to develop resistance to Dictyocaulus filaria. This susceptibility resulted in a greater proportion of the Soay ewes developing heavy burdens of these lung worms, and in a greater proportion of the yearlings and ewes excreting D filaria larvae in their faeces.


Increased stimulatory capacity of spleen cells from adult thymectomized mice in mixed lymphocyte reactions. Conflicting results have been reported concerning the effect of adult thymectomy (A-Tx) on the mixed lymphocyte reaction (MLR) response. Our purpose was to test the reverse question, namely the effect of A-Tx on the stimulatory capacity of mouse lymphocytes carrying allelic disparities at the Mls and the H-2 loci. Spleen cells from A-Tx CBA donors were found to be significantly more stimulating than cells from normal donors. That A-Tx could eliminate suppressor T cells involved in MLR regulation or in preventing back stimulation is not likely according to our data. An increment in expression or in accessibility of Mls or H-2 antigenic determinants induced by A-Tx is no more likely, since a smilar increase in lymphocyte proliferation was observed in syngeneic cultures. The most probable explanation remains that A-Tx discloses a strongly stimulatory subpopulation, perhaps acting in part nonspecifically. The hypothesis of an enrichment in B cells versus a loss of T cells is not compatible with our findings, since B-cell-enriched fractions from various origins never attained the stimulating ability disclosed by A-Tx cells. Moreover, the cell involved is theta-positive, although slightly nylon-wool-adherent, and thus shares several properties with immature T cells involved in auto-rosette formation.


Prognosis of chronic obstructive lung disease in relation to radiology and electrocardiogram. Survival in relation to radiological and electrocardiographical changes was examined in a retrospective study of 228 hospital patients aged 40-69 years with a FEV1 of 1.5 1 or less, and a FEV1 of 70% or less of the vital capacity due to chronic obstructive lung disease. The only radiological changes which influenced survival after 4 years were enlarged heart and pronounced dilatation of the pulmonary artery. Thirty-eight percent of the patients with normal ECG but with pronounced dilatation of the pulmonary artery were alive after 4 years. In patients with normal ECG and normal or moderate dilatation of the pulmonary artery about 80% had survived after 4 years. There was only 18% survival after 4 years in patients with abnormal ECG and pronounced dilatation of the pulmonary artery and/or with enlarged heart, and only 6% in patients from age group 60-69. In patients with abnormal ECG without enlarged heart and without pronounced dilatation of the pulmonary artery 50-63% had survived after 4 years. Pulmonary hyperinflation was not important for survival during the first 4 years.


Systemic hypertension, left ventricular hypertrophy and myocardial infarction in patients with chronic obstructive lung disease. Left ventricular function was evaluated prospectively during 1 year in a controlled clinical study of 73 patients with chronic obstructive lung disease. The control group comprised 68 patients matched for age and sex and with no evidence of airways obstruction. Left ventricular hypertrophy was found in 52% and systemic hypertension in 58% of patients in the study group compared with 6% and 15% respectively in the controls. Left ventricular hypertrophy was diagnosed in 70% of patients with chronic bronchitis and in 19% of those with chronic emphysema. Systemic hypertension was observed in 45% of the bronchitic type patients and in 81% of those with emphysema. The incidence of myocardial infarction in the study group was not lower than in the controls. The high frequency of left ventricular hypertrophy in patients with chronic obstructive lung disease can probably be related to a similar high frequency of systemic hypertension. Hypertension per se does not explain left ventricular hypertrophy in all patients with chronic bronchitis, but hypoxemia and acidosis seem to be of pathogenetic importance in these cases.


The aromatic ethylamide derivative of retinoic acid in the treatment of acne vulgaris. A clinical trial on the aromatic ethylamide derivative of retinoic acid (Ro. 11-1430) applied topically was carried out for 10 weeks on 50 ambulatory patients suffering from various degrees of acne vulgaris. This clinical trial assessed the efficacy and side reactions of Ro. 11-1430 in the treatment of acne vulgaris, especially when used in the tropics. A comparison was made between the results obtained in this trial and those in another trial using topical retinoic acid. Analysis made in terms of efficacy, drug tolerance, patients' complaints and duration of treatment for achieving obvious alleviation of symptoms shows that Ro. 11-1430, with the exception of side reactions due to the drugs applied, was inferior to retinoic acid. Relapses as well as remissions often occurred during the period of maintenance therapy. Like retinoic acid, Ro. 11-1430 has a palliative effect only and not a curative one.


Huntington's chorea in the Cape coloured community of South Africa. Huntington's chorea is a grave genetic neurological disorder which appears to be a more serious problem in South Africa than has generally been recognized. The minimum prevalence of the disease in the Cape Coloured is 3,5/100 000 of the population. Sixteen per cent of patients were younger than 20 years at the time of onset of the disease. This is among the highest incidence of juvenile Huntington's chorea in the world. The gene for Huntington's chorea has been in South Africa for 300 years. It was first introduced into this country from Holland in the middle of the 17th century and then later from England in the middle and end of the 19th century. The number of affected individuals appears to be on the increase in South Africa. Unfortunately, at present, no methods are available for effective control of this disorder.


Is there a significant gene dose effect in the primed lymphocyte test? Pig lymphocytes typed for products of the MHC were primed in vitro against allogeneic lymphocytes. When rechallenged with a panel of different cells, specific 'typing' responses were distinguishable which were not obscured by high non-specific responses or by a restimulator gene dose effect. A gene additive effect was observed in both primary MLR and in the primed lymphocyte test (PLT).


Correlation between magnitude of MLC and kidney graft survival in intrafamilial transplantation. The role of HLA-A and-B and HLA-D compatibility was analyzed in 63 recipients of intrafamilial kidney grafts. At 1 year post-transplantation the survival of grafts from HLA-A and-B compatible donors was 89% and that of grafts from HLA-A and/or-B incompatible donors 77%. Recipents with a Relative Response (RR) in MLC of less than 20% towards their donors, indicating HLA-D compatibility, had a 4-year graft survival of 100%. After 1 year the graft survival of this group was statistically different (p less 0-01) from the 63% graft survival of recipients with an RR greater than 60%. An RR greater than 60% indicates HLA-D incompatibility between recipient and donor. For patients with RR less than 60% the 2-year graft survival was 46%. This was lower than that of patients with RR less than 20% (P less than 0.001) and that of patients with an RR of 20--60% (P less than 0.01). The recipients with an RR of 20--60%, indicating slight HLA-D incompatibility with their donors, had a 2-year graft survival of 88%. We concluded that graft survival was correlated to the magnitude of MLC response between recipients and donors in such a way that a high MLC response indicating HLA-D incompatibility was associated with a high frequency of graft rejection while a low MLC response was associated with graft survival. HLA-D compatibility correlated with an excellent outcome in five cases in spite of HLA-A and-B incompatibility.


On the HLA-B,D map distance.

On the HLA-B,D map distance. HLA--A,--B,--C and--d typing and intra-familial MLC studies in 21 couples and their 91 children revealed three B, D recombinants in 165 informative haplotypes. This corresponds to a B,D map distance of 1.8 centiMorgans, which is somewhat higher than previous estimates based on intra-familial MLC chessboard experiments. All three recombinants are maternal.


[Study on hematological toxicity in irradiation and ICRF 159 combination treatment during experimentation on animals with particular consideration of long-term effects (author's transl)]. Experiments on animals are utilized for the control of hematological toxicity in sound NMRI mice during and after fractionated ICRF 159 therapy, fractionated whole-body irradiation and a combination of both. In the course of the 32-day therapeutic phase, and also during the total follow-up period lasting 196 days, continual determination of leukocytes and thrombocytes was performed. Leukocyte and thrombocyte depression is related to radiation effects during the phase of therapy and subsequently. In the later period of follow-up, however, hematological toxicity developed by ICRF 159 is higher than that produced by irradiation. Early and late effects of the preparation must be distinguished therefore. The thrombocytopenic effect is altogether less pronounced than the leukocytopenic effect. Here, too, the thrombocytopenic action of ICRF 159 appears in the course of the late phase only, but then more distinctly. The present results are discussed and compared to hitherto existing observations from animal experimentation and from clinical findings described in literature.


[ATPase activity and processes of calcium transport in membranes of sarcoplasmic reticulum of skeletal muscles with E-avitaminotic dystrophy]. Peculiarities of functioning of the sarcoplasmic reticulum muscles membranes with E-avitaminotic distrophy were studied. It was determined that the level of ATP-dependent consumption of Ca2+, value of the Mg2+, Ca2+-ATPase activity and an amount of the intermediate phosphorylated product forming in the reaction of ATP hydrolysis decrease. The rate of this product formation in the sarcoplasmic reticulum of the distrophic muscles is inhibited as compared to normalcy. Elimination of Ca2+ into calcium-free medium from the vesicular membranes of the reticulum preliminarily loaded with Ca2+ occurs more rapidly under dystrophy than in normalcy. The data obtained evidence for a disturbance of mechanism of Ca2+ active transport and for an increase in the membrane permeability for Ca2+ in the membranes of the dystrophic muscles sarcoplasmic reticulum. A problem is considered on a dependence of the skeletal muscles observed in the reticulum under dystrophy of the functional changes on the membrane structure, in particular on their lipid composition.


A human tubular array plasma cell.

A human tubular array plasma cell. A human plasma cell is described which is distinct with both the light and electron microscope. With indirect immunofluorescence its cytoplasm is immunoglobulin-associated and the ultrastructure is characterized by tubular arrays of endoplasmic reticulum similar to those described in a number of diseases. Hypotheses regarding these tubular structures are reviewed.


Ultrastructure of the liver in a case of childhood cystinosis. Ultrastructural findings in the liver in a case of childhood cystinosis are reported. Crystalline structures were found mainly in Kupffer cells. The presence of dark cells, with or without crystals, was the most striking feature observed. Such cells have already been noted within the kidney on one occasion when it was shown that the dark substance was L-cystine (Spear et al., 1971). In this case identical dark material was also found extracellularly. The data shows that free cystine can fill cell cytoplasm and extracellular spaces and the possibility that cystine overproduction may take place in the hyaloplasm should be considered. Extracellular location of cystine in the tubules might account for an increase in epithelial permeability and thus for the Fanconi syndrome.


Heterotopic striated muscle on the surface of the brain. Heterotopic tissue, identified by both light and electron microscopy as cardiac muscle, was detected at autopsy on the surface of the right superior temporal gyrus of a 73-year old female patient. The cells of the heterotopic tissue were interconnected by intercalated discs and the fibres contained regularly cross-striated, contracted, or relaxed myofibrils indicating a continuing contractile activity until the time of death.


Partial purification of epidermal G2 chalone. A partial purification of epidermal G2 chalone from crude epidermal cell extracts from hairless mice is described. The procedure involved the sequential use of ammonium sulphate precipitation, affinity chromatography and gel filtration. Mitosis-inhibiting activity at each stage in the purification was tested in an in vitro assay system employing human epidermoid carcinoma cells in exponential growth phase and Colcemid (Ciba) for arresting mitoses. This assay system is much more rapid and convenient than conventional in vivo systems. By the procedure described, a 10,000-fold material purification of the active component has been obtained. This corresponds to a 3,000-fold purification measured by protein content, and a 300-fold increase in mitosis-inhibiting activity per unit we;ght. The active component is acidic, contains sugar residues and has gel chromatographic properties characteristic of a substance with molecular weight of approximately 20,000. On SDS polyacrylamide gel electrophoresis, however, three weak bands were found. The active component is resistant to trypsin and protease and stable between pH 6.0 and 8.5. It is easily inactivated at pH values below 6.0. At the present stage of purification, several components other than the active one still remain in our material and further purification steps must be eventually employed.


[The place of laparoscopy in the investigation of infertility (author's transl)]. An assessment of the value of hysterosalpingography (HSG) and laparoscopy was made on the basis of a comparison of the respective findings obtained during routine investigation of 105 women attending the Infertility Clinic. The results of the two procedures concurred in 76% of the women; in the remaining cases, apparently normal findings on HSG had to be rectified on the basis of laparoscopic investigation and vice versa. The divergent results are discussed in detail. In particular, intramural obstruction of the tubes diagnosed on HSG often appears to be merely functional and the presence or absence of adhesions in the region of the tubes must be viewed with reservation. HSG and laparoscopy should be considered complementary, not rival procedures.


[Mechanisms of the antilipemic action of niacin]. In tests conducted with albino rats the influence of nicotinic acid, nicotinamide, hydrocortisone and their combinations on a number of factor characterizing directly or indirectly the state of the lipid metabolism in the liver was investigated. It is suggested that hormonal mediation (preliminary stimulation of the suprarenals) may play a significant part in the realization of hypolipemic activity of niacin, its concrete mechanism being oxidation of the lipids, controlled by corticosteroids.


[The post mortem alterations of myofibrilar proteins and adenosintriphosphatase activities of the skeletal muscles (author's transl)]. Immediately after the death of rabbits and at different times within 48 hours, we took out a part of the psoas muscle, from which we made myofibrilar preparations. The carcasses providing the muscle samples were held at two different temperatures. One group was held for 48 hours at 25 degrees C, imitating room temperature. The other group was held for 12 hours at 25 C degrees and at 25 C degrees and 12 hours at 10 C degrees, imitating daily temperature changes. Each myofibrilar sample was subjected to SDS-polyacrylamide gel electrophoresis. In addition we determined the Ca++ activated and the EGTA inhibited ATPase specific activity of the myofibrils. We found that within 48 hours the myofibrilar proteins were subjected to some characteristic proteolytic changes, which were dependant on the environmental temperature. The most interesting change was found in carcasses held constantly at 25 C degrees for 48 hours, where the EGTA inhibited ATPase activity was increased to about seven times its initial value, reflecting impairment of the troponin complex.


[Significance of laparoscopy in decisions on the preventive therapy of various ovarian tumors in girls]. Of 125 laparoscopies, carried out in the Clinic of Surgical Gynaecology in the years 1972 to 1974, 12 referred to girls aged from 15 to 18 years (9,6%). As a consequence of the mentioned diagnostic-therapeutic procedure 6 girls (50%) avoided laparotomy. Laparoscopy is an excellent technique to establish diagnosis in cases of ovarian tumours especially in the developmental age.


[Detection of pathogenic Enterobacteriaceae in seawater]. As a result of investigations carried out in the littoral sea waters (a total of 114 sea water samples were analyzed) there were isolated 226 strains of salmonellae referred to 9 serological types, this constituting 35% of the positive samples. As revealed, salmonella distribution in sea water depended on the site of outflow of sewage, and also on the unfavourable influence of rivers inflowing to the littoral part of the sea.


[Study of the circulation of Crimean hemorrhagic fever virus in Turkmenistan]. Final results of the virological and serological investigations of the circulation of the Crimean hemorrhagic fever virus in the Turkmenian SSR carried out in 1968-1976 are presented in this report. In the examination of 2294 blood serum samples of human beings complement binding antibodies against the Crimean hemorrhagic fever were revealed in 0.4% of cases. It was revealed that five species of ixodes ticks could he infected with this virus; for the first time its strains were also isolated from the Hyalomma dromedarii ticks. Isolation of the Crimean hemorrhagic fever virus from ticks and determination of the precipitating antibodies against this virus in agricultural animals--from 6.2 to 11.1%--in all the regions of the republic pointed out that the natural nidi zones were widespread at the territory of the Turkmenian SSR, and that it was necessary to carry out further study of the given focus.


[Alkaline phosphatase and ATPase activity in the walls of the cerebral vessels in hypertension and arteriosclerosis with disorders of the cerebral circulation]. In hypertensive disease and atherosclerosis without acute disorders of cerebral circulation it was established that in the cerebral vessel walls there was a high activity of alkaline phosphatase and adenosintriphosphtase. In the symmetrical areas of the subcortical nodes differences in the activity of these enzymes were insignificant and not valid. In vessel walls, located in the peripheral zone of the apoplectic hemorrhage and in the adjacent brain tissue the activity of alkaline phosphatase and adenosintriphosphatase drops. The existence of a high activity of enzymes in the vessel walls on the early stages of hemorrhages gives ground to the authors to claim that in the peripheral zone of an extensive hemorrhage a drop in the enzyme activity appears in the process of a development of a stroke.


A simple uroflowmeter for routine use.

A simple uroflowmeter for routine use. A simple uroflowmeter has been constructed which, according to the experience gathered so far, can be used satisfactorily for the urodynamic examination of the lower urinary tract.


[Action of acetylcholine on the adenosine triphosphatase activity of the brain synaptosomes of the suslik, Citellus erythrogenus]. In experiments in vitro at 37 and 17 degrees C, studies have been made of the effect of ACh upon the activity of Mg- and Na,K-ATPase of brain synaptosomes of the ground squirrel in summer animals and during winter hibernation. ACh (6 mM) decreases the activity of ATPases by 23-33% at 37 degrees C. During winter hibernation, the inhibitory effect of ACh is increased resulting in lower values of residual ATPase activity after the effect of ACh as compared with those obtained in summer period.


Mucopolysaccharide heterogeneity of the reptilian kidney basement membranes. The kidney basement membranes of fifteen different reptiles from marine, terrestrial, desert, amphibious and fresh-water habitats have been analysed for their mucopolysaccharide contents histochemically, employing well-known and recent techniques. Capsular and tubular basement membranes possess only neutral mucopolysaccharides; on the other hand glomerular basement membrane possesses both neutral and acidic (sialic acid) mucopolysaccharides. The concentration of different mucopolysaccharides seems to be dependent on the type of habitat. Their possible physiological significance in the kidney function is discussed in great details.


Cytochemical localization of adenosine triphosphatase and thiamine pyrophosphatase in the synapases of rat's cerebral cortex. Ultrastructural distribution of adenosine triphosphatase and thiamine pyrophosphatase in synapses of rat's cerebral cortex was studied. Adenosine triphosphatase activity in some synaptic vesicles and mitochondria, on pre- and postsynaptic membranes, as well as in the postsynaptic thickening was established. The reaction specificity was proved by means of some controls: various concentrations of ouabain, NaF, NiCl2, cysteine, substrate free medium and non-specific substrates - cocarboxylase and beta-glycerophosphate. At the thiamine pyrophatase reaction, the enzyme positive product was found on the membrane of some clear synaptic vesicles, on the singl sacs of smooth endoplasmic reticulum in the axon terminal, and bouton cell membrane. Substrate free medium, addition of cystein and substitution of orininal substrate with adenosine triphosphate and beta-glycerophosphate as controls were used. The fine structure localization of both enzymes in synaptic structures suggests their important role in the synaptic function.


Depression of spasticity by alpha-adrenergic blockade. In spastic patients the alpha-adrenergic blocking drug thymoxamine (Opilon Forte) was found capable of depressing most propioceptive reflex parameters within 1 min after intravenous administration. The action seems to be of CNS origin, probably exerted as a depression of spindle stretch sensitivity through descending alpha-adrenergic bulbospinal pathways, but an additional action on the mechanism of presynaptic inhibition is likely. With oral administration, the drug is also capable of depressing distressing clonus, and it is concluded that it deserves further testing as a spasmolytic.


An electromic differential pressure flowmeter and a resistance meter for continuous measurement of vascular resistance. An electronic differential pressure flowmeter for mean blood flow measuring and its use in a resistance meter for continuous recording of vascular resistance is described. The flowmeter allows accurate and linear registration also in the small flow range (less than 10 ml/min), thus appropriate for use in small experimental animals.


Congenital aortic stenosis. A retrospective study on 32 operated patients. The magnitude of the peak systolic pressure gradient (PSPG) over the aortic valve was often determining factor when deciding for or against operation of the congenital aortic stenosis. The impression that PSPG alone was an inadequate parameter for assessment of the degree of stenosis was supported by the present retrospective analysis of 32 patients operated upon for this anomaly. A gradient of 75 mmHg or more indicates a tight stenosis but a lower value does not exclude a pronounced constriction of the orifice, any more than does absence of symptoms or signs of left ventricular hypertrophy (LVH) on the ECG. It is probably not only the size of the stenotic orifice that determines the prognosis in aortic stenosis but also other factors, e.g. function of the left ventricular myocardium. A hypothesis was put forward by one of us (M. V.) that the location of the valvular ostium, central or peripheral, can be of importance and that turbulence-induced vibrations of the left ventricular wall may depress the myocardium. Differences in the pathoanatomy of the stenotic aortic valves did not explain the poor correlation between e.g. symptoms or LVH and PSPG or the size of the remaining orifice in the present study.


Some psychological effects of physical disability. It has long been recognized that people who become severely disabled go through two stages (denial, mourning) before adjusting to their disability. Negative aspects of these stages, such as dependence and hostility, are viewed as logical outcomes within a society that perpetuates an ideology of normality, where disability is perceived as evidence of negative status. The prerequisites of self-acceptance are examined together with their implications for rehabilitation and re-entrance into the community.


Assessing the driving potential of the handicapped. Proper and early assessment of the handicapped person's potential for driving a vehicle depends upon an understanding of the factors involved in a driver evaluation. The driver evaluation factors discussed in this paper are: driving aids and their application; the handicapped driver's physical, perceptive, and cognitive capabilities; and the psychosocial characteristics that influence a client's ability and need for driving.


[Secretory immunoglobulin A].

[Secretory immunoglobulin A]. Secretory IgA is the prevailung immunoglobulin on the mucous membranes of different tissues. It is a polymer immunoglobulin and in comparison to the serum IgA the secretory IgA has a additional polypeptide chain, the secretory component. The secretory IgA is synthesized locally in the mucosa. Secretory IgA is a very important factor in the immune defence of the mucous membranes. Secretory antibodies are regulated independently from serum antibodies. They show a virus neutralizing effect and activities against bacteria and lifeless noxa. The mechanism is not yet clear. It is possible, that the reaction of the secretory IgA with the antigen prevents settlement of microorganisms on the mucous membranes. The clinical importance of secretory IgA is undoubted especially the deference of the mucosa in cases of a virus infection.


[Quantitative immunochemical determination of human secretory IgA]. Secretory IgA from human colostrum was fragmented by mercaptoethanol. The heavy chain fraction was prepared by means of gel chromatography on Sephadex G 100 in 1 N acetic acid. After immunization of rabbits with this heavy chain fraction the resulting antiserum contained antibodies specific for the alpha-chain and antibodies against the secretory component. These antibodies were separated by means of immunosorption. The antibodies against the secretory component precipitate free secretory component as well as bound secretory component. The antiserum is suitable for quantitative determination of secretory IgA, but free secretory component reacts too. Also secretory IgM may react, because secretory IgM contains up to 70% secretory component.


[Skin tests in the diagnostic of allergic alveolitis (author's transl)]. Cutaneous tests used in the diagnostic of allergic alveolitis are reviewed. The results indicate, that cutaneous tests are useful only bird breeders lung. Usually there is dual reaction: 1st type I and 2nd type III. The basic immunologic mechanismus of the skin test results and thereby of the diseases are discussed.


[Lymphocyte transformation test in the diagnosis of occupational allergy (author's transl)]. In 139 persons occupationally exposed to compounds of chromium, formaldehyde and p-phenylenediamine lymphocytic transformation test (ltt) was performed to detect a delayed-type hypersensitivity. In patients suffering from either contact dermatitis or allergic respiratory diseases the findings of ltt were concordant only in about one third of the cases in comparison to patch testing, intracutaneous test, nasal provocation or inhalation test.


Differential binding activity of EA receptor bearing human lymphocyte subpopulations. Two types of EA rosettes were studied in rheumatoid arthritis patients and control subjects. Heterologous (rabbit) and homologous (anti-D) antibody sensitized human red blood cells (EAr and EAh, respectively) were used for examining the EA binding capacity of human lymphocytes. Both control and rheumatoid arthritis blood samples yielded significantly lower EArRFC levels as compared to the percentage of EArRFCs, the difference being even more expressed with control lymphocytes. No difference, however, was observed in the case of tonsillar lymphocytes, as equal rosette levels were reached in both systems used. Introduction of immunosuppressive therapy resulted in a temporary dissociation of the two rosette values EAr and EAh binding lymphocytes were differently affected by aggregated human IgG, only the latter ones being inhibited, contrasting with the equal inhibitory action of purified Fc fragments. Reducing the density of anti-D antibodies on the surface of erythrocytes, the EAh rosette count dropped to the level of EAr RFCs. The data suggest an activity-depending Fc receptor distribution resulting in different binding capacity for more or less sensitized indicator RBCs.


[Clinical and immunological effect of washing powder enzymes on workers and users (author's transl)]. For 141 workers in the washing powder industry in Maribor (Group A) and 68 workers of vegetables' shops to determine the risk of sensitization for house-wives handling enzymes detergents (Group B) as a control group the results of diagnostic investigations as well as analyses of protective measures to proteolytic enzymes are contrasted. Within the Group A eight subgroups according to exposition to proteolytic enzymes powder are evaluated. Especially elucited are the results of skin testing (Scratch-tets with Maxatase, Alcalase and culture extract from B. subtilis) and with proteolytic enzymes powder, the lung function tests (vitalogram, spirogram, pneumometer-test diffusion-test and sometimes the blood gas tests), cytological examinations of nasal mucosa and simultaneously taking a blood sample for determination of concentration of total serum IgE and precipitins to enzymes extracts.


Local specific immunity in infants with spastic bronchitis and bronchopneumonia. In 27 infants with spastic bronchitis and in 23 infants with bronchopneumonia the values of IgA, IgG and IgM in bronchial secretion were determined by single radial immunodiffusion method. In both group A and B the frequencies of IgA and IgG were statistical significant. The IgM frequency was significant only in group A. The mean values of IgA and IgG were considerably higher in relation to mean IgM values. The presence of IgA and IgG was found in the first bronchial secretion sample in all investigated infants. The presence of IgM in bronchial secretion was found in high percentage. However, the presence of IgM was found in ten investigated infants only in second bronchial secretion sample. It was concluded that for estimation of real state of specific local immunity on bronchial mucosa it is necessary to determine the immunglobulin values twice and that at three days interval. In this study the local immunoglobulin deficiency was found in none case.


[Age dependence of adjuvant arthritis in rats (author's transl)]. The age dependence of elicitation of adjuvant arthritis in three different strains of rats is recorded. In contrast to the existing literature an adjuvant disease can be elicited already in animals of 13 to 15 days of age, where significant, obvious genetical differences exist between the used strains with regard to age dependence of the occurence of arthritis. From the results is to conclude, that in all investigations on adjuvant arthritis merely genetically identic animals are to be used, and the possibility of strain dependent differences in the assessment of the results are to be considered.


The advances of hyposensibilisation therapy in bronchial asthma patients allergic to house dust antigen. The hyposensibilisation therapy was realized in a population of 72 adult asthma patients allergic to house dust, feathers and molds. In this number 52 patients were treated by aqueous extracts of allergens produced by Pasteur Institute in Paris (20 patients by house dust extract only) and 20 patients by D. pteronyssinus tyrosine adsorbate (Migen Bencard). The very good and good results of hyposensibilisation were observed in 67.3% of cases receiving the aqueous extracts of allergens and in 80% of cases treated by Migen. Side effects of such form of therapy were not observed. The extract of house dust mite emulsified in tyrosine is, in the authors opinion, expecially successful in the treatment of atopic asthma patients sensibilized to inhalant allergens.


Comparative study of social and psychological analyses in asthmatic, rheumatic and diabetic children. The authors have analysed clinically, biochemically, immunologically, psychologically and socially three groups of children with chronic diseases using special perforated cards with 49 data for each illness. All data have registered in special passport for each child. 278 children with bronchial asthma were medically, socially and psychologically compared to 27 rheumatic and 19 diabetic children. All statistical calculations showed significantly higher disturbances in asthmatic and diabetic children than in rheumatics.


[Immune responses and blood group genetics in patients with asthma bronchiale (author's transl)]. The combination of MN(Hp 2-2) blood group is more frequent in bronchial asthma patients than in the normal population. The highest changes of blood serum proteinogramm were observed within the first week after anti-typhus-paratyphus-tetanus vaccination in persons with haptoglobulin of 2-2 type, especially in combination with NN and MN blood groups of MN system. The most intense increase of antibody titer to typhoid bacillus was observed in a month after the vaccination in persons with 2-2 type of haptoglobin.


Fluorochemical resin complexes for use in solvent repellent hand creams. A fluorochemical (FC)-resin complex has been developed for use in protective hand creams. Hand creams incorporating this new technology effectively repel solvents and resist their penetration into the skin. The in vitro studies conducted to determine the efficacy of the formulated FC-resin complex include solvent penetration through treated filter paper, solvent repellency on treated pigskin, and penetration of radio tagged sodium lauryl sulfate through treated hairless mouse skin. In vivo studies demonstrate that this new technology does aid in reducing irritation caused by solvent contact.


Thromboembolism in mitral porcine valve recipients. A low incidence rate of thromboembolism has been reported in mitral porcine valve recipients. In contrast, 5 of 22 single mitral porcine valve recipients (23 percent) followed up in our clinic for a mean of 16 months had thromboembolic events. All patients but one were receiving long-term anticoagulant therapy. One thromboembolic event resulted in death, three in permanent neurologic deficits and one in a peripheral arterial occlusion. All five patients with emboli had atrial fibrillation and left atrial enlargement. Three had thromboembolic events before porcine heart valve implantation. In addition, five mitral porcine valve recipients who were not receiving anticoagulant therapy were examined at autopsy. Thrombus was identified in the left atrium in three patients, at the tissue-valve interface (sewing ring) in two, on the porcine valve cusps in one and in the right atrium in one. Factors influencing thrombus formation such as left atrial enlargement, atrial fibrillation and a prosthetic device are present after mitral porcine valve implantation and are indications for long-term anticoagulation therapy.


Skin lesions in viral hepatitis: histologic and immunofluorescent findings. A variety of skin rashes are knowned to occur as a part of the serum sickness-like prodrome of acute viral hepatitis which is thought to be due to immune complex deposition. We report the histologic and immunofluorescent findings in the skin and the seroloigc abnormalities in a patient with both erythematous maculopapular and purpuric rashes. We found circulating hepatitis B surface antigen (HBsAg), hypocomplementemia and cultaneous vasculitis associated with deposition of immunoglobulin and complement in the skin. We could not demonstrate intradermal deposition of HBsAg, but the findings are consistent with the immune complex hypothesis.


The role of lactogenic hormones in the pregnant woman and the fetus. Evaluation of the roles of prolactin and placental lactogen in pregnancy in primates has revealed mammotropic, fetal osmoregulatory, metabolic, and steroidogenic roles, which appear to protect the uterine contents during late pregnancy and prepare the fetus for the changes in nutrition at the time of delivery.


The effect of systemic infusions of dehydroisoandrosterone on the distribution of uterine blood flow in ovine pregnancy. The effects of systemic infusions of dehydroisoandrosterone (6 mg.) on endogenous estrogen production and subsequent changes in regional blood flows and cardiac output were studied in six pregnant ewes at 105 to 128 days of gestation. Blood flows were measured with radionuclide-labeled microspheres. Plasma estrone concentrations increased from (mean +/- S.E.M.*) 27 +/- 2 to 117 +/- 13 pg. per mililiter, while estrodiol rose from 34 +/- 5 to 72 +/- 5 pg. per mililiter (p less than 0.05). Associated increases in blood flow occurred in endometrium, myometrium, and unimplanted uterine caruncles, while blood flow to the placental cotyledons  was not significiantly changed. Perfusion was also increased in the Fallopian tubes, mammary gland, cervix, and vagina, the greatest fractional increase in blood flow occurring in the latter two, 387 and 456 per cent (p less than 0.005), respectively.


Ethinyl estradiol administration and plasma steroid concentrations in ovariectomized women. The effect of ethinyl estradiol treatment on the plasma levels of cortisol, corticosterone, deoxycorticosterone, progesterone, testosterone, dehydroepiandrosterone sulfate, delta4-androstenedione, and estrone was studied in eight women. All the subjects had undergone ovariectomy and hysterectomy at least one year prior to this study. The systemic concentration of cortisol and the binding of cortisol were significantly increased, paralleling the increased transcortin concentration due to ethinyl estradiol treatment. Corticosterone concentration was also significantly increased after three days of estrogen administration and this level continued to be higher than normal as long as patients were treated with estrogens, but there was no change in the plasma concentration of deoxycorticosterone. The plasma levels of progesterone testosterone, dehydroepiandrosterone sulfate, delat4-androstenedione and estrone or the ratio of estrone to delta4-androstenedione did not change with ethinyl estradiol treatment. These observations suggest that the administered estrogen increased the transcortin concentration and had only a limited effect on adrenocortical steroidogenesis.


Insulin effects on monovalent cation transport and Na-K-ATPase activity. The effects of insulin on monovalent cation transport and on Na-K-ATPase activity from intact cells, tissue homogenates, and purified enzyme of the avian salt gland were studied. Monovalent cation active transport, measured by ouabain-inhibitable 86Rb+ uptake, was significantly increased (21.9 +/- 7.3% SE) in tissue slices exposed to insulin (100 mU/ml) for 15 min. A small but significant (12.2 +/- 1.9%) increase in Na-K-ATPase activity was similarly observed after salt gland tissue slices were exposed to insulin. This increase in enzymatic activity did not occur when broken-cell homogenates were exposed to insulin. Purified preparations of Na-K-ATPase showed no insulin enhancement of activity either in the presence of optimal or less than fully activating Na+ and ATP concentrations. Na-K-ATPase activity was the same in detergent-activated homogenates of both control and insulin-treated slices, consistent with insulin activation of existing enzyme sites. These data support the hypothesis that at least part of the increase in monovalent cation active transport produced by insulin is related to enhanced Na-K-ATPase activity and indicate that the latter phenomenon is dependent on some components or properties of the intact cell.


Evidence of 5-HT participation in vagal inhibitory pathway to opossum LES. Studies were performed in anesthetized opossums to investigate the nature of vagal-stimulated sphincter relaxation, which is resistant to antagonism by a combination of hexamethonium and atropine. The sphincter pressures were measured with water-filled and continuously perfused catheters anchored in the lower esophageal sphincter. Neither increase in the doses of hexamethonium and atropine nor addition of diphenhydramine further modified the vagal response. However, administration of 5-methoxydimethyltryptamine in the presence of hexamethonium and atropine abolished vagally stimulated sphincter relaxation. In animals pretreated with parachlorophenylalanine, addition of atropine and hexamethonium also abolished vagally stimulated sphincter relaxation. In the experiments in which lower esophageal sphincter relaxation on vagal stimulation was abolished, the local stimulation of intramural neurons still produced normal lower esophageal sphincter relaxation. These studies suggest that 5-hydroxytryptamine may participate in the vagal inhibitory pathway to the lower esophageal sphincter.


Normal cardiac myosin ATPase and mechanics in pressure overload with digitalis treatment. Cardiac muscle myosin ATPase activity is depressed and contractile function impaired when the heart is subjected to a chronic pressure overload. Administering digitalis in the presence of chronic pressure overload significantly attenuates the decline in mechanical function. The current study sought to determine if the cardiac muscle myosin ATPase activity of cats treated with digitalis in the presence of pressure overload remains normal in parallel with the mechanical function. Four groups of cats were studied: normal controls (C), animals with pressure-overload hypertrophy with or without failure (HF), normal cats that received treatment with digitalis (D), and animals that received digitalis prior to and together with pressure overload (DHF). Compared to C, the maximum myosin ATPase activity of HF was significantly (P less than 0.05) depressed, but the maximum ATPase activity of D and DHF was not altered significantly (P greater than 0.05) from C. In parallel with the enzyme maximum activity, the papillary muscle isometric rate of force development was significantly (P less than 0.005) depressed in HF compared to C; D and DHF were not significantly (P greater than 0.05) different from C. It is concluded that the depression of myosin ATPase observed in HF is not present when digitalis is administered concomitant with the pressure overload.


Sodium valproate in Huntington's disease. The authors assessed the effect of sodium valproate, which is thought to elevate brain gamma-aminobutyric acid (GABA) levels, in the treatment of Huntington's disease by an objective ultrasound method in three patients with Huntington's disease. Despite plasma levels ranging from 47.0 to 140.8 microgram/ml (mean, 104.7), sodium valproate had no beneficial effect on involuntary movements. The authors stress the importance of activation to achieve a standard level of arousal in the assessment of involuntary movements.


An "in vitro" system for the study of rat spermatogonial proliferative control. The effect of a "testicular extract" on spermatogonial proliferation in adult rats is comparatively studied both "in vivo" and "in vitro". Both in irradiated rats injected with "testicular extract" as in testicular fragments from irradiated rats incubated in culture medium, addition of "testicular extract" elicits an inhibition in thymidine-H3 uptake by type A spermatogonia. This is not the case for non irradiated rats or incubation of testicular samples from non irradiated animals after addition of "testicular extract". The "in vitro" system for assay of the spermatogonial chalone is used to analyze the general characteristics of this mitotic inhibitor.


Microculture method for mixed lymphocyte cultures in the horse. A miniaturized method for the mixed lymphocyte culture test in the horse is described. The test is performed in either round- or flat-bottom microtitration tissue culture plates. Concentrations of responsing and stimulating cells are varied, depening on the experiment. Significant discrimination between isogeneic and allogenic mixtures is possible after 120 hours' culture when cells are labeled ([3H]thymidine) for the last 16 to 18 hours of the test.


Down's syndrome: a ten-year group study. Thirty individuals with the clinical diagnosis of Down's syndrome received ophthalmologic examination periodically over 10 years at a state school for exceptional children. External examination, retinoscopy, anterior segment evaluation, ophthalmoscopy, and tonometry were usually done. The ages at present range from 10 to 50 years. The sex ratio was 80% male and 20% female. Three subjects died during the course of the study. The most frequent ocular anomalies were oblique fissures, refractive error, blepharoconjunctivitis, epicanthus, and Brushfield's spots. All of these occurred in 50% or more of the subjects.


A new nerve stimulator for monitoring neuromuscular blockade and performing nerve blocks. A new stimulator is described with characteristics designed to take advantage of recent knowledge of the pharmacology of neuromuscular relaxants and events involved in normal neuromuscular transmission. The stimulator has proven as useful in performance of peripheral nerve blocks as in monitoring neuromuscular blockade.


[The evaluation of auditive incapacity, handicaps and disability: principles, definition, and general formula of evaluation (author's transl)]. After having defined auditive incapacity, handicaps and disability, the authors will show that the scales which join these to auditive loss in dB follow a general biological law. From this law, it is possible to define a theorical scale for each of these cases which could serve as a comparison with the actual scales.


A new concept of the aetiology and surgical repair of paraumbilical and epigastric hernias. The aetiological factors concerned in the production of paraumbilical and epigastric hernias have been reviewed along structural--functional lines. A positive relation between the aponeurotic pattern and herniation was demonstrable at operation in 25 patients with paraumbilical or epigastric hernias. The effect of abdominal distension, obesity, and straining are discussed. A new type of surgical repair planned on this basis is described. The preliminary results obtained with this technique are reported, with a discussion of other previously described types of surgery.


Down syndrome, paternal age, maternal age and birth order. Recent cytogenetic evidence has shown that trisomy 21 can arise, perphaps even in substantial proportion, from paternal nondisjunction. The statistical association between Down syndrome incidence and maternal age, paternal age and birth order has been studied in a sample of over 4000 cases. The size of this sample made it possible to control for the effect of maternal age by single years of age during the search for a paternal age effect and vice versa, and the importance of such stringent control is emphasized. The maternal age association was confirmed with an extremely high degree of statistical significance while no independent effect of paternal age was found; indeed, the rates at paternal ages over 45 years appear to be nearly constant. After adjusting for the effects of parental age, a significant inverse association of birth order with incidence was noted. It also appears that the incidence among very young mothers may be high: for maternal ages 15 years and less the rates seem to be equivalent to those found at 30 or 35 years. In order to help answer the question of whether the maternal age association is the result of increasing rates of nondisjunction or of some other mechanism (for example, an age related defect in a spontaneous abortion screening mechanism), the proportion of cases due to maternal and paternal nondisjunction at different parental ages must be determined.


[Streptoverticillium griseoviridum n. sp., a producer of the candidin-amphotericin B group, antifungal heptaene nonaromatic antibiotic 0185]. An actinomyceteous strain LIA-0185 producing a heptaenic non-aromatic antibiotic of the candidin type was isolated from a soil sample taken in the Georgian SSR under the programme of screening antifungal antibiotics. The taxonomic study of the strain showed that it belonged to the series of viridoflavum and had the following main taxonomic features: the sporophores in the whorls, straight, remote: the aerial mycelium from yellow to dark-olive-grey; the substrate mycelium olive; the soluble pigment absent; the melanine pigment was produced on the peptone medium; the culture formed H2S; assimilated glucose, mannose, inozide and to a lesser extent fructose; did not assimilate arabinose, xylose, sucrose, lactose, ramnose and raffinose. The strain inhibited the growth of yeast and fungi, grampositive bacteria and actinomycetes and produced a complex of non-aromatic heptaenic antibiotics. The actinomycete differed from the other whorl cultures. It was classified as a new species Sv. griseoviridum sp. nov. The antibiotic complex was a mixture of 2 components, i. e. I and II present approximately in equal amounts. Component II was analogous to candidin. Component I was a new original substance.


Percutaneous cervical cordotomy.

Percutaneous cervical cordotomy. Cordotomy should be reserved for patients with intractable pain resistant to conservative treatment that is not of a dysaesthetic type. The high cervical percutaneous technique permits exploitation of the principles of stereotactic surgery, especially physiological localization of the lesion site. The induction by 100 Hz stimulation of a warm or cool tingling in some portion of the contralateral half of the body without muscle tetanization ensures location within the spinothalamic tract while attention to the somatotopographic organization of the responses permits a certain degree of tailoring of the extent of analgesia to the patient's needs. During 264 consecutive procedures the spinothalamic tract was successfully located in 99% with a 0.3% incidence of significant persistent paresis.


Percutaneous radiofrequency facet denervation. Percutaneous RF facet denervation is a valid, low-risk means of treating 'mechanical' pain syndromes in previously unoperated patients with back and/or leg pain. In the series of 126 patients, reported long-term overall success was 42%. With improved technique and patient selection, success rate has increased to 67%. This procedure appears to be increasing in clinical value as a more conservative means of treating certain back pain problems, thus avoiding definitive surgery.


Percutaneous radiofrequency lumbar rhizolysis (rhizotomy). Low-back pain may arise from degenerative changes in the posterior joints of the lumbar spine. These joints are innervated by a branch of the posterior primary ramus, which follows an antomically constant course. Pain impulses from these joints can be interrupted by coagulating the nerve with a radiofrequency wave, the probe having been placed in the area of the nerve percutaneously. Percutaneous lumbar rhizolysis was carried out under local anesthesia on an outpatient basis in 82 patients, most of whom had multiple level rhizolysis, Rhizolysis was successful in 67% of patients with mechanical low-back pain without evidence of disc herniation and nerve-root compression or psychogenic pain, who had not previously undergone an operation for relief of the pain.


Ultraviolet phototherapy and photochemotherapy of acne vulgaris. The therapeutic value of various ultraviolet treatments was assessed in patients with moderately severe papulopustular acne. The results did not verify the common belief that ultraviolet radiation is highly beneficial. In no instance was the comedo count appreciably reduced. Modest improvement was observed with sunburn rays (UV-B) and slightly more with the combination of long ultraviolet radiation (UV-A) and UV-B. UV-A alone had the least effect. Photosensitization with coal tar and UV-A greatly aggravated acne and was notably comedogenic. Photosensitization with methoxsalen (8-methoxypsoralen) applied topically was neither harmful nor helpful.


Angiolymphoid hyperplasia with follicular mucinosis. Follicular mucinosis is described to our knowledge for the first time in angiolymphoid hyperplasia. In general, follicular mucinosis may be regarded as a peculiar, nonspecific histological reaction pattern in follicular epithelium that may occur on its own or in association with other pathological processes, particularly lymphomas. The unusual and characteristic features of angiolymphoid hyperplasia revealed by electron microscopy are irregular vessels lined by atypical endothelial cells with convoluted nuclei and large cytoplasmic vacuoles.


Woolly hair nevus. Two case reports and a discussion of unruly hair forms. Woolly hair is very curly hair that is characteristically unruly and will not form naturally into locks. Woolly hair nevus first appears when the scalp hair begins to grow. It is seen as a patch of unruly, very curly hair, arising in a field of otherwise unremarkable scalp hair. Woolly hair can also be seen as a hereditary trait involving the entire scalp and in acquired forms. It may be distinguished from two other types of unruly hair, pili torti and spun glass hair.


Erythrokeratodermia variabilis. A family study. Erythrokeratodermia variabilis is a rare genodermatosis; American authors have reported only four previous cases. It had been a problem to obtain a large pedigree for clinical investigation. We studied a family with 12 involved members in five generations. Symmetrically distributed migratory patches and scaling plaques are characteristic and were found to involute with a combination of keratolytic agents and topical steroids. Exacerbations of these patches and plaques were noted in our female patients during such high estrogen states as pregnancy or oral contraceptive usage.


Treatment of pneumatosis cystoides coli by oxygen inhalation. Endotracheal intubation and intermittent positive pressure ventilation were used to overcome the difficulties of oxygen therapy for pneumatosis cystoides coli in a 9-year-old child with Down's syndrome and a congenital heart defect. As compared to previously reported cases, a shorter duration of treatment and a lower arterial oxygen tension proved successful.


Vasopressin: route of administration and effects on canine hepatic and superior mesenteric arterial blood flows. BLOOD FLOWS THROUGH THE CANINE HEPATIC (HBF) AND SUPERIOR MESENTERIC ARTERIES (MBF) WERE MEASURED WITH ELECTROMAGNETIC FLOWMETERS, DURING INFUSIONS OF VASOPRESSIN, BY THREE ROUTES OF ADMINISTRATION: 1) intra-hepatic-arterially (IHA), 2) intra-portal-venously (IPV) and 3) intra-systemic-venously (IV). Mean control HBF was 148 +/- 17 (S.E.) ml min(-1); MBF was 243 +/- 27 ml min(-1); aortic pressure (AP) was 126 +/- 3 mm Hg; portal venous pressure (PVP) was 8.8 +/- 1.0 mm Hg. Infusions of vasopressin, at a rate of 5 x 10(-3) units kg(-1) min(-1), IHA, reduced HBF significantly (p < .001) to 121 +/- 21 ml min(-1), within one minute. Flow returned to control, despite continued drug infusion; and at the end of the fifth minute of infusion, the value (134 +/- 21 ml min(-1)) was not significantly (p > .05) different from control. During the same infusion, MBF fell to 129 +/- 28 ml min(-1) (p < .001), by the sixth minute of the infusion and remained at this level for the duration of the infusion. AP increased to 137 +/- 13 mm Hg, by the sixth minute of the infusion and was sustained at this level for the duration of the infusion. PVP decreased to 7.0 +/- 1.0 mm Hg, by the tenth minute of the infusion. The responses to IPV vasopressin were indistinguishable from those following IHA vasopressin, with the exception that HBF was reduced to only 147 +/- 22 ml min(-1) (from a preinfusion control of 160 +/- 23 ml min(-1)), at one minute. HBF returned to control, despite continuation of the infusion. IV vasopressin, at the same concentration, caused no change in HBF throughout the ten minute infusion. These observations indicate that the canine hepatic arterial circulation responds to vasopressin with vasoconstriction characterized by autoregulatory escape. By any of the three routes of administration, vasopressin causes a significant and sustained reduction in blood flow through the superior mesenteric artery. Autoregulatory escape, from vasopressin-induced mesenteric arterial constriction, is not observed. Based on these observations, significant changes in mesenteric arterial blood flow can be anticipated without associated significant changes in hepatic arterial blood flow, regardless of the route of administration of vasopressin.


Late failure in vein grafts: mediating factors in subendothelial fibromuscular hyperplasia. Late failure of autologous vein grafts often results from excessive subendothelial fibromuscular hyperplasia. Varying factors have been implicated in this process, but the exact etiology remains unclear. In this study, three groups of animals were studied which had sections of common carotid artery replaced with autologous vein grafts. Group I had simple replacement, while Groups II and III had grafts supported by either tightly woven or loose mesh dacron prostheses. Thrombosis occurred only in the unsupported grafts. Unsupported grafts also had more subendothelial proliferation when compared to the loose mesh group. The combined thickness of the intima-media correlated inversely with the number of vasa present within the vein graft wall, i.e. significantly more vascularization was found in the mesh supported group when compared to the other groups. Grafts supported with the tightly woven prosthesis were relatively impervious to the ingrowth of vasa vasora. The data suggest that persistent distension of the graft wall by intra-arterial pressure influences the degree of subendothelial fibromuscular hyperplasia and may be interrelated to revascularization of the graft wall per se.


A new personal monitoring device for the detection of beta-propiolactone and other alkylating agents. A personal monitoring badge has been developed for the detection of the direct-acting, alkylating carcinogen beta-propiolactone at atmospheric concentrations as low as 6 ppb for 24-hour and 0.6 ppm for 0.25-hour exposure. The method employs the trapping reagent p-nitrobenzyl pyridine (p-NBP) absorbed on a cellulose thin-layer chromatography (TLC) strip. Deoxyguanosine can be used in place of p-NBP, but its lower limit of detection is 60 ppb for 24-hour exposure. The authors also obtained positive results with the carcinogens bis (chloromethyl) ether, chloromethyl methyl ether, diepoxybutane, dimethylcarbamoyl chloride, ethyleneimine, and glycidaldehyde. In practice, the TLC strip is positioned in a filmbadge holder. The TLC strip monitoring badges are easy to prepare; they should encounter no resistance of personnel to their use since they are not cumbersome. Monitoring at the end of an exposure is simple and requires no expensive equipment or specialized personnel.


Vascular disease in infective endocarditis. Report of immune-mediated events in skin and brain. A patient with subacute bacterial endocarditis, who had a prosthetic mitral valve, exhibited hypocomplementemia, mixed (IgG, IgM) cryoglobulinemia, and widespread dermal vasculitis with IgM deposited at the dermoepidermal junction. Postmortem findings included immune-complex glomerulonephritis and deposits of IgG in the choroid plexus. These findings are consistent with a generalized vasculitis, which may be mediated by circulating immune complexes; basement membrane localization of immune complexes to the skin and choroid plexus appears not to be specific for systemic lupus erythematosus, as has been previously thought, but may represent the general phenomenon of immune-mediated pathogenesis.


[The value of myocardial mass determination in the evaluation of left ventricular functional value in chronic mitral insufficiency. Apropos of 44 cases]. The functional value of the left ventricle in chronic mitral incompetence, determined as a function of haemodynamic and angiocardiographic indices, has now become a difficult factor to determine because of the multiplicity of indices which exist, and because of disagreement about the pathological values which are often a function of the valvular pathology in the particular case. Moreover, the importance of myocardial hypertrophy is rarely taken into account. The ratio systolic work/myocardial mass (WS/WM) which lies between no limits in the normal subject (0.81+/-0.03 gm.g-1) has allowed us to classify 44 patients with chronic mitral incompetence into three groups: groupe I (WS/V(M) greater than 0.87 gm.g-1), characterised by an increase in WS proportionally superior to that of V(M) (hyperfunctional); group II (0.87 gm.g-1 larger than or equal to WS/V(M) larger than or equal to 0.75 gm-1), characterised by a parallel increase of mass and WS (isofunctional); group III (WS/V(M) less than 0.75 gm.g-1) in which the increase in mass is proportionally greater than the variation in WS (hypofunctional). A comparison between the selectivity of this relationship and that of other indices, which contain large areas of overlap between the various groups of patients, lead us to hope for a prognostic index which will take account of the myocardial mass and of the pump action of the left ventricle.


[Arrhythmias following closure of atrial septal defects. Apropos of 300 cases]. In a series of 300 cases whose atrial septal defects were closed (268 with ostium secundum, 27 with ostium primum, and 5 cases with both), arrhythmias were found in 60%. These were usually slow supraventricular arrhythmias caused by substitution (51%), and less commonly rapid supraventricular arrhythmias (27%), extra-systoles (16%), disorders of atrio-ventricular conduction of second and third degree and disorders of the auricle (6%). Conduction disorders were significantly more common (p less than 0.001) after closure of ostium primum (37%) than after closure of an ostium secundum (4.5%). Arrhythmias are most common during the first week (56%), and are usually of the slow type, and during the three succeeding weeks are markedly less frequent (31%) with a higher proportion (p less than 0.001) of the rapid type. No one anatomical type of ASD was complicated with arrhythmia more than the others. The slow type of arrhythmias occurred in the high ASDs, and the fast type especially amongst elderly patients. Longterm follow-up showed arrhythmias in 28% of patients with an ostium secundum defect. The factors influencing arrhythmias were age, cardiac enlargement, and the mean pulmonary arterial pressure. Arrhythmias were just as common in cases with a small shunt.


Hepatic blood flow measurement.

Hepatic blood flow measurement. Although many experimental studies have been made to determine the total hepatic blood flow in steady circulatory states, very few have been done in unsteady states of either circulatory overload or underload. In this experiment, a comparison is made between total hepatic blood flow measured by the single injection of indocyanine green and the electromagnetic flow methods in the dog, in which circulatory overload was induced by dextran 40 infusion. While there was close correlation between the values obtained by the two methods in normal dogs, following dextran infusion the indirect indocyanine green method overestimated hepatic blood flow by 40% to 60%, using the electromagnetic method as a comparison standard. The reason for this discrepancy is not elucidated by these studies.


Muscle and subcutaneous oxygen tension. Measurements by mass spectrometry after sympathectomy. Utilizing the mass spectrometer, tissue oxygen tension (TPO2) in the resting state was measured in the extremities of ten dogs before and after lumbar sympathectomy. Although there was considerable variation between individual dogs, significant changes in tissue oxygenation were not consistently obtained in the group as a whole, althouth femoral arterial blood flow increased in all animals. Using TPO2 changes to estimate perfusion, no significant increase in nutritive flow could be demonstrated.


[New method of abdominal wall incision in autopsy]. The incision of the anterior abdominal wall proposed by the author is begun (after dissection of thoracic tissues on the median line) from processus xyphoideus sterni and led toward left regio iliacae (on the straight line or first on the left regio hypogastricae to its middle, then on liniae pararectalis) approximately till the middle of ligamentum Pouparti. Then from the lower end of this incision a transversal incision of superpubica is made at an angle, about 4--6 cm above simphysis ossium pubis, in adults 15--20 cm long. This incision provides a wide access to the organs of the small pelvis, demonstration of their changes on the spot, goes aside from median wounds or scars, and permits to penetrate from the transversal incision along the subcutaneous cellular tissue to the organs and tissues of regio subpubica.


Fibrinolytic properties of some optic nerve vessels. The fibrinolytic activity of posterior ciliary arteries (PCA), dural vessels (DV), central retinal vessels (CRV), and pial plexus (PP) in 18 human eyes was studied by the fibrin-slide technique and PAS staining. Acitvity was measured on the basis of the minimal incubation time at which lysis appeared. A constant pattern of fibrinolytic activity was found. The PCA were the most active, followed by DV, CRV, and PP. With consideration of the assumed antithrombotic role of fibrinolysis, the results suggest that PCA are better protected against occlusion than CRV.


The history of avian medicine in the United States. IV. Some milestones in American research of poultry parasites. Most of the major contributions of Americans to knowledge of poultry parasites have been made in the last 100 years. Factors responsible for this tardiness differed somewhat according to the disease. The first parasitic diseases to receive attention were usually those with distinctive characteristics as well as serious consequences, such as "gapes" and lousiness. Since helminths could usually be readily observed, whereas protozoa could be observed only by persons skilled in microscopy, disorders attributable to the former usually received attention earlier than did protozoan diseases. The control of ectoparasites, before the use of modern insecticides, became vastly simplified as mechanical incubators and brooders replaced the hen, and as the birds were provided with better housing. The major contributions of Americans to our understanding of parasitic diseases of poultry are detailed for five disorders attributable to helminths, and two attributable to protozoa. The latter are histomoniasis of turkeys and coccidiosis of chickens. No attempt has been made to evaluate the impact of contemporary research.


Tryptophan and the control of plasma glucose concentrations in the rat. 1. Injection of L-tryptophan (750 mg/kg body wt.) led to pronounced hypoglycaemia in fed and 48 h-starved rats. 2. The hypoglycaemic effect is blocked by pretreament with p-chlorophenylalanine, compound MK-486 [Carbidopa: L-alpha-(3,4-dihydroxybenzyl)-alpha-hydrazinopropionic acid monohydrate] or methysergide, and potentiated by pargyline. 3. 5-Hydroxy-L-tryptophan is more potent and induces a more rapid hypoglycaemia than does tryptophan. Other tryptophan metabolites were not associated with hypoglycaemia. 4. Adrenalectomy increases, and acute experimental diabetes strongly decreases, the sensitivity of rats to tryptophan induction of hypoglycaemia. Diabetic animals were also insensitive to 5-hydroxytryptophan. 5. Metabolite concentration changes in the livers from tryptophan-treated 48h-starved and diabetic animals were consistent with a rapid inhibition of gluconeogenesis. This did not correlate with the hypoglycaemic response. 6. Tryptophan treatment was associated with a significant increase in the plasma [beta-hydroxybutyrate]/[acetoacetate] ratio; there were no changes in the plasma concentrations of urea, triacyglycerol, non-esterified fatty acids and glycerol. 7. These observations suggest that the hypoglycaemic action of tryptophan is mediated through formation of intracellular 5-hydroxytryptamine, and is unrelated to the inhibition of gluconeogenesis. It is unlikely that this increased synthesis of 5-hydroxytryptamine involves directly either the adrenal glands or the central nervous system.


Cardiac-muscle hypertrophy. Differentiation and growth of the heart cell during development. An experimental model for the study of the control of tissue growth by cell proliferation (hyperplasia) and cell enlargement (hypertropht) is proposed. The model is constructed on the basis of the fact that, when DNA replication and cell proliferation cease in cardiac muscle during neonatal development, subsequent growth of the ventricular tissue is due to cell enlargement. The time period during development when this change in growth pattern occurs is documented with the cessation of DNA replication and the synthesis and accumulation of myosin as biochemical parameters. It is suggested that adrenergic innervation of the heart may be the physiological signal that changes the growth pattern of the muscle from hyperplasia to hypertrophy.


A simple and rapid method for the reversible removal of lipids from a membrane-bound enzyme. A simple, rapid and reproducible method for the reversible removal of lipids from a membrane-bound enzyme is described. Essentially, a membrane preparation containing (Na+ + K+)-dependent adenosine triphosphatase was extracted with the non-ionic detergent Lubrol WX in the presence of glycerol, and partial separation of protein from lipid was achieved with the use of only two centrifugations. About 74% of the endogenous phospholipid and 79% of the cholesterol were removed, concomitant with a virtually complete loss of ouabain-sensitive adenosine triphosphatase activity, but with retention of 60-100% of the K+-dependent phosphatase activity. The addition of pure phosphatidylserine re-activated the enzyme to more than 80% of the initial activity, and up to 30% of the protein was recovered. Excess of phosphatidylserine could be washed off the enzyme to give a stable 'reconstituted' preparation. The effects of variation in the experimental conditions were examined, and the results are discussed with respect to the possibility of adapting the method to the study of other lipid-dependent enzymes bound to membranes.


Ouabain binding to phospholipid-dependent adenosine triphosphatase. The role of phospholipid in the binding of ouabain to the (Na+ + K+)-dependent adenosine triphosphatase was studied. Enzyme preparations obtained from rabbit kidney were treated with Lubrol WX to remove the phospholipid component essential for ATPase activity. Reconstituted enzyme samples were prepared by the addition of phosphatidylserine and sedimentation of an enzymically active lipid-protein complex. The binding of ouabain to both kinds of preparations was measured under equilibrium conditions with the use of 3H-labelled ouabain and initial ouabain concentrations in the range 0.01-1 micrometer. The main findings were: (i) (Mg2+ + Pi) promoted binding of significant quantities of ouabain only to the reconstituted enzyme; (ii) the absence of added Na+, (Mg2+ + ATP) similarly promoted binding only to the reconstituted samples; (iii) the addition of Na+ in the presence of (Mg2+ + ATP) increased the amount of ouabain bound to the reconstituted enzyme when the ouabain concentration was below about 0.1 micrometer, but it had no effect when the ouabain concentration was about 1 micrometer; (iv) (Mg2+ + ATP) induced ouabain binding to the depleted enzyme only when Na+ was also added; (v) the amount of ouabain bound to both depleted and reconstituted enzymes was the same in the presence of (Mg2+ + ATP + Na+); (vi) the reconstituted enzyme appeared to have a greater affinity for Na+ than did the depleted enzyme.


Thermal denaturation of Micrococcus lysodeikticus adenosine triphosphatase. Influence of temperature on the circular dichroism, fluroescence and enzymic activity of the protein. The soluble ATPase (adenosine triphosphatase) from Micrococcus lysodeikticus underwent a major unfolding transition when solutions of the enzyme at pH 7.5 were heated. The midpoint occurred at 46 degrees C when monitored by changes in enzymic activity and intrinsic fluorescence, and at 49 degrees C when monitored by circular dichroism. The products of thermal denaturation retained much secondary structure, and no evidence of subunit dissociation was detected after cooling at 20 degrees C. The thermal transition was irreversible, and thiol groups were not involved in the irreversibility. The presence of ATP, adenylyl imidodiphosphate, CaCl2 or higher concentrations of ATPase conferred stability against thermal denaturation, but did not prevent the irreversibility one denaturation had taken place. In the presence of guanidinium chloride, thermal denaturation occurred at lower temperatures. The midpoints of the transition were 45 degrees C in 0.25 M-, 38 degrees C in 0.5 M-and 30 degrees C in 0.75 M-denaturant. In the highest concentration of guanidinium chloride a similar unfolding transition induced by cooling was observed. Its midpoint was 9 degrees C, and the temperature of maximum stability of the protein was 20 degrees C. The discontinuities occurring the the Arrhenius plots of the activity of this enzyme had no counterpart in variations in the far-u.v. circular dichroism or intrinsic fluorescence of the protein at the same temperature.


The subunit structure of the arom multienzyme complex of Neurospora crassa. Evidence from peptide 'maps' for the identity of the subunits. Evidence was obtained, from polyacrylamide-gel electrophoresis in the presence of urea and from peptide 'mapping' of specifically labelled cysteine-and methionine-containing peptides, that the two subunits of the arom multienzyme complex of Neurospora crassa are chemically very similar and possibly identical.


Immunogenetical aspects of multiple sclerosis with special regard to the HLA-histocompatibility system. In the HLA complex it is evident that some antigens occur rather frequently, while others are rare. A statistically significant increase or decrease of any of these antigens in a given number of patients suffering from the same disease therefore suggests an association between such a disease and the HLA-system. In this study the Author compared the HLA antigen frequencies of 1.000 M.S. patients and 1.000 healthy controls, tissue typed during the same time period by the identical antiserum-set.


HLA typing on Italian multiple sclerosis population. Considerable evidence suggests the existence of significant differences of HLA distribution between M.S. patients and normal healthy subjects of the same population. In the present work we investigate whether the antigen DW2 may be a better marker for M.S. than the specificities at the loci A and B by means of in vitro one-way mixed lymphocyte cultures.


Application of teem-test for investigations of cellular immune phenomena in multiple sclerosis. Some evidence is presented for usableness of tanned erythrocytes in electrophoretic mobility (TEEM)-test. Two possibilities of application of TEEM-test for immunological investigation in multiple sclerosis are discussed: detection of lymphocyte sensitization against a soluble antigen (3 M KCl extracted) derived from a normal brain and measurement of mixed lymphocyte reactin (MLR) after a short-time lymphocyte culture. Results show some connection between autosensitization (TEEM-test using normal tissue antigen) and predisposition (TEEM-MLR-test).


Changes in the pulmonary arteries of the rat during recovery from hypoxia-induced pulmonary hypertension. Pulmonary hypertension has been induced in rats by 2 weeks' exposure to hypoxia, equivalent to an altitude of approximately 5500 m, in a hypobaric chamber. The rats were removed from the chamber and allowed to recover for up to 8 weeks at atmospheric pressure. Precise quantitative microscopic techniques after injection of the pulmonary artery have been used to estimate the regression in the pulmonary artery of the structural changes associated with pulmonary hypertension. During recovery the degree of muscularization of the pulmonary arteries decreases by disappearance of muscle cells from the small arteries and a drop in arterial wall thickness of larger vessels. These changes do not seem to reflect pulmonary artery pressure directly, since right ventricular hypertrophy regresses at a faster rate. In hypertensive rats there is a "loss" of small arteries in the alveolar region and little filling of precapillary vessels. On recovery, some of the vessels fill, suggesting that encroachment on the lumen by muscle and endothelial cells has lessened. Even after 8 weeks' recovery, however, some arteries do not return, suggesting they have completely disappeared and that regions are left with relatively little perfusion. This reduction of vascular reserve presents without there being right ventricular hypertrophy.


Enhancement of comedogenic substances by ultraviolet radiation. Ultraviolet radiation enhanced the capacity of human sebum, sulphur, cocoa butter, squalene, and coal tar to produce comedones in the external ear canals of rabbits. An enhancement of the comedogenicity of coal tar and squalene was similarly demonstrated in man. We conjecture that in occasional patients sunbathing may aggravate acne by augmenting the comedogenicity of sebum.


The Sézary syndrome lymphoid cell: abnormal surface properties and mitogen responsiveness. The peripheral blood lymphoid cells of five patients with Sézary syndrome (SS) were examined with respect to their surface membrane characteristics and their response to mitogens. These cells showed markedly defective mitogenic responses to a broad dose range of phytohaemagglutinin (PHA), pokeweed mitogen, concanavalin A, and a rabbit antihuman lymphocyte antiserum (ATS), when compared with normal human lymphocytes. SS lymphoid cells (three patients studied) also displayed diminished or nearly absent capacity to form rosettes with unsensitized sheep erythrocytes (E-rosettes), and lacked surface immunoglobulin determinants. Despite their poor mitogenic response to ATS, they were as susceptible as normal lymphocytes to ATS-induced, complement mediated cytotoxicity. By comparison with lymphocytes from patients with chronic lymphocytic leukaemia, however, SS lymphoid cells showed decreased susceptibility to leukoagglutination by PHA. By way of contrast, three patients with mycosis fungoides having normal-appearing peripheral blood lymphocytes showed normal lymphocyte responses to mitogens, as well as normal proportions of E-rosette forming and surface immunoglobulin-bearing lymphocytes. These studies demonstrate that the SS lymphoid cell may, in some cases, lack surface properties and mitogen response characteristics of both B- and T-lymphocytes.


Binding of ATP and of 1,N6-ethenoadensone triphosphate to rabbit muscle phosphofructokinase. The binding of 1,N6-ethenoadenosine triphosphate (eATP) to rabbit muscle phosphofructokinase has been studied by fluorescence and circular dichroism, and compared with that of its counterpart, ATP. Muscle phosphofructokinase binds 11.3 +/- 1.2 mol of epsilonATP per tetramer with an average dissociation constant of 60 micrometer. This is in aggreement with the report of 3 ATP binding sites per phosphofructokinase protomer (Kemp & Krebs, 1967). The binding of epsilonATP is relatively homogeneous in comparison with the biphasic binding of ATP. Saturating concentrations of ATP, GTP, and ADP displace about 80% of the bound epsilonATP from the enzyme, whereas FruP2 and AMP displace only 27%. Citrate, on the other hand, enhances the affinity of phosphofructokinase for epsilonATP. The effects of the binding of ATP and epsilonATP on the conformation of enzyme have also been compared. Binding of ATP results in increases in both the lcoal rigidity and the ellipicity of the tryptophanyl side chains, whereas binding of epsilonATP causes a slight decrease in the local rigidity and has virtually no effect on the ellipticity.