Ribonucleic acid stimulation of mammalian liver nuclear-envelope nucleoside triphosphatase. A possible enzymic marker for the nuclear envelope.

1. The specific activity of rat and pig liver nuclear-envelope nucleoside triphosphatase (EC 3.6.1.3) decreases when the system is depleted of RNA. The activity can be restored by adding high concentrations of yeast RNA to the assay medium. 2. Exogenous RNA also increases the activity of the enzyme in control envelopes (not RNA-depleted). The effect appears to be largely specific for poly(A) and poly(G); it is not stimulated by rRNA or tRNA preparations, ribonuclease-hydrolysed RNA, AMP, or double- or single-stranded DNA. 3. Inhibitors of the enzyme, in concentrations at which half-maximal inhibition of the enzyme is achieved, do not affect the percentage stimulation of the enzyme by yeast RNA. 4. The simulation is abolished by the inclusion of 150 mM-KCl or -NaCl in the assay medium, but not by increasing the assay pH to 8.5. 5. The results are discussed in the light of the possible role of the nucleoside triphosphatase in vivo in nucleo-cytoplasmic ribonucleoprotein translocation. 6. It is proposed that poly(G)-stimulated Mg2+-activated adenosine triphosphatase activity should be adopted as an enzymic marker for the nuclear envelope.


The activation of sodium-plus-potassium ion-dependent adenosine triphosphatase from marine teleost gills by univalent cations.

The apparent affinity constants for the binding of Cs+, Rb+, K+, Li+, Tl+ and NH4+ to (Na+ + K+)-dependent adenosine triphosphatase from teleost gills were measured and the values discussed in terms of the ion-selectivity isotherm described by Eisenman & Krasne (1975) [in MTP International Review of Science: Biochemistry Series One (Fox, C.F., ed.), vol. 2, pp. 27--59, Butterworths University Park Press, Baltimore]. The ion selectivity of the present enzyme is remarkably similar to that from nerve and brain.


Calcium ion-dependent myosin from decapod-crustacean muscles.

Ca2+ regulation of arthropod actomyosin adenosine triphosphatase is associated with both the thin filaments, as in vertebrates, and with the myosin, as in molluscs. The actomyosin of decapod-crustacean fast muscles was previously considered to be an exception, displaying only a Ca2+-regulatory system linked to the thin filaments and not a myosin-linked regulatory system. In the present study, myosin regulation is demonstrated in a variety of decapod muscles when they are tested under more physiological ionic conditions. Myosin regulation is shown by using mixtures of pure rabbit actin with myofibrils, with actomyosin and with purified myosin, and in each case the adenosine triphosphatase is Ca2+ dependent. Myosin regulation may also occur in vertebrate striated muscle, but seemingly is lost during purification of the myosin.


The subunit structure of rabbit skeletal-muscle phosphofructokinase and the amino acid sequence of the tryptic peptide containing the highly reactive thiol group.

1. The single highly reactive (class I) thiol group per 80000-mol.wt. subunit of skeletal-muscle phosphofructokinase was specifically carboxymethylated with iodo[2-14C]acetate, and after denaturation the remaining thiol groups were carboxymethylated with bromo[2-3H]acetate. After tryptic digestion and peptide 'mapping' it was found that the 14C radioactivity was in a spot that did not contain significant amounts of 3H radioactivity, so it is concluded that there is not a second, 'buried' cysteine residue within a sequence identical with that of the class-I cysteine peptide. 2. The total number of tryptic peptides as well as the number of those containing cysteine, histidine or tryptophan were inconsistent with the smallest polypeptide chain of phosphofructokinase (mol.wt. about 80000) being composed of two identical amino acid sequences. 3. The amino acid sequence of the tryptic peptide containing the class-I thiol group was shown to be Cys-Lys-Asp-Phe-Arg. This sequence is compared with part of the sequence containing the highly reactive thiol group of phosphorylase.


Kinetic properties of the primary inhibitor of plasmin from human plasma.

The interaction of human plasmin with the newly discovered alpha2-plasmin inhibitor was investigated. It was found from rate measurements that the reaction involves the rapid formation of a first enzyme-inhibitor complex, followed by the slow irreversible transition to another complex. L-Lysine influences the first step, but not the second.


[Hypothesis and experimental confirmation of a new pharmacological model of osteoarthrosis (author's transl)].

Basing on the fact that in adult articular cartilage there is an equilibrium of anabolic and catabolic processes, we developed a hypothesis that an experimentally induced reduction of anabolic reactions will lead to degenerative alterations in joint cartilage. In our experiments using monoiodine acetate, a potent inhibitory substance, we could confirm that 6-8 weeks after intraarticular injection into the knee joint of hen arthrotic processes can be observed in cartilage. By macroscopical, histological and biochemical criteria these arthrotic degenerations are in good correlation with human osteoarthrosis. Our new experimental model of osteoarthrosis in laboratory animals appears to be very sutiable for the study of degenerative articular processes and for pharmacological tests of new antiarthrotic drugs.


Muscle pain following administration of suxamethonium to pregnant and non-pregnant patients undergoing laparoscopic tubal ligation.

The frequency of muscle pain following suxamethonium was studied in 50 pregnant (8-13 weeks' gestation) and 100 non-pregnant women, undergoing laparoscopic tubal ligation. The incidence of muscle pain in the non-pregnant group was 42%, but only 20% in the pregnant women. The intensity of fasciculation was less in the pregnant patients. It appears that pregnancy protects the patient from suxamethonium pains, even during the first trimester.


Electrical stimulation in chronic low-back pain.

Since 1972, 367 patients with chronic low-back pain have been treated by electrical stimulation (e.s.). Patients with herniated disc lesions and spondylitis and allied conditions were included. Following e.s. 75-100% pain relief was obtained by 53% of the patients 50% pain relief by 27% and there was no improvement in 20% of patients. In a follow-up of 208 patients, 6-36 months later, approximately 70% stated that pain relief was similar to that obtained at the end of treatment.


Acne vulgaris: an investigation into the number of anaerobic diphtheroids and members of the Micrococcaceae in normal and acne skin.

A quantitative study was made of the microflora of 174 acne and 68 non-acne subjects. Two groups of organisms were investigated, the anaerobic diphtheroids and members of the Micrococcaceae. The results showed high numbers of both groups of bacteria in skin bearing blackheads, papules or pustules and in non-acne adolescent skin. There were significantly lower numbers of bacteria in the pilosebaceous ducts of normal looking skin in acne areas and in pre-adolescent skin when compared with non-acne adolescent skin. It is suggested that increased numbers of bacteria alone do not predispose to acne, but that their interaction with the skin, which is a function of the localized skin environment, may be important.


[Energization of membrane vesicles from the cells of glycolyzing bacterium Streptococcus faecalis].

Membrane fractions were isolated from Streptococcus faecalis cells of a glycolyzing microorganism, devoid of the respiratory chain, using the methods of osmotic shock of the protoplasts, ultrasonic treatment of the cells and ultrasonic treatment of the protoplasts. All fractions possessed the ATPase activity, the highest activity being observed in the fraction isolated by ultrasonication of the protoplasts. All preparations were estimated with respect to the presence of vesicles, formed by the "inside-out" and "inside-in" membranes, using ATPase as a marker of the membrane orientation. In the membrane fractions obtained by ultrasonication of the protoplasts, the "inside-out" vesicles were prevalent. ATP-dependent energization of the membranes, sensitive to the action of dicyclohexylcarbodiimide and tetrachlorotrifluoromethyl benzimidazole, was demonstrated by measuring the transport of the lipophylic anion of phenyldicarbaundecaborane and aniline naphthalene sulfonate fluorescence.


[Study of the kinetics and mechanism of ATP hydrolysis by soluble ATPase of the chloroplasts (CFl) in the presence of Mg2+ ions].

A kinetic study of ATP hydrolysis by soluble ATPase of chloroplasts (CF1) was made. At low concentrations of MgCl2 a linear increase of the reaction rate was observed during the increase in the ATP concentration up to 1 mM. At high concentrations of MgCl2 the dependence was of a more complicated nature. At MgCl2 concentrations lower than 0.1 mM the reaction approached second-order kinetics with respect to Mg2+; the increase in MgCl2 concentration resulted in a decrease of the reaction order. It is assumed that MgATP is the "true" substrate and MgADP the "true" inhibitor of the reaction. A reaction mechanism of ATP hydrolysis  is postulated.


Pattern detection by mongol and non-mongol subnormals.

Ten mongols and ten clinically heterogeneous subnormals matched on chronological age, mental age and digit span took part in an experiment in which tape-recorded supra-span digit sequences with different patterns were presented. There were six patterns: random, mirror (e.g. 583385); same-digit pairs (e.g. 558833), same-digit throughout (e.g. 333333), couplet repetition (e.g. 585858) and triplet repetition (583583). The numbers of digits correctly recalled in any order by the mongols in the various conditions ranked from least to most were: random, mirror, same-digit pairs, same-digit messages, triplet repetition and couplet repetition. The rank order for the non-mongols was the same except that the positions of couplet and triplet repetition were reversed. Mongols had significantly poorer recall for random, mirror and same-digit pair messages than non-mongols but were their equals in other conditions. The mongols' performance was more sensitive to pattern than the performance of the other subjects. There was some evidence that, in the messages with same-digit pairs and the same digit throughout, all subjects (but mongols in particular) tended to insert new digits into the response sequence and that the digit introduced was the next one in simple arithmetic progression. It would appear that the hypothesis about poor auditory-vocal channelling capacities of mongols needs qualification.


Antagonism of biogenic amine-induced depression of cerebral cortical neurones by Na+, K+-ATPase in inhibitors.

The effects of iontophoretically applied Na+-, K+-dependent adenosinetriphosphatase (Na+,K+-ATPase) (EC 3.6.1.3) inhibitors (ouabain, digitoxin, digitoxigenin, strophanthin K, strophanthidin, thevetin A and B, ethacrynate, and harmaline) on the depression of rat cerebral cortical neurones by noradrenaline, 5-hydroxytryptamine, and histamine have been studied. The inhibitors antagonized depressions of spontaneously active neurones evoked by these amines, but not those evoked by gamma-aminobutyric acid, adenosine, adenosine 5'-monophosphate, or calcium. The antagonistic potencies of the various inhibitors appeared to be proportional to their known potencies as inhibitors of Na+, K+-ATPase. The data therefore support the hypothesis that amines depress central neurones by activating an electrogenic sodium pump.


Thymidine labeling index of human breast carcinoma. Enhancement of in vitro labeling by 5-fluorouracil and 5-fluoro-2'-deoxyuridine.

Inhibitors of thymidylate synthetase, 5-fluoro-2'-deoxyuridine (FUDR) and 5-fluorouracil (FU), enhanced in vitro thymidine labeling of human breast carcinoma cells. Their use resulted in an increase in the measured thymidine labeling index (TLI) of breast carcinomas by increasing detectability of labeled nuclei in autoradiographs. The TLI was measured with FU or FUDR enhancement in primary breast carcinomas from nine women younger than age 50, and from 30 women 50 years or older. The mean and geometric mean TLI were 8.0 and 6.3 respectively for the younger group, and 4.0 and 2.8 respectively for the older group. Similar significant age-associated differences were noted in a series of 133 TLI measurements without FU or FUDR. The TLI was not significantly correlated with primary breast carcinoma size or number of axillary nodal metastases. The capacity to form axillary metastases must be related to factors other than the rate of cell replication in breast carcinomas.


Calcium accumulating and ATPase activity of cardiac sarcoplasmic reticulum before and after birth.

The possibility that the cardiac SR undergoes developmental changes at about the time of birth, and that these changes affect its ability to accumulate Ca2+ and to hydrolyse ATP has been studied. SR-rich microsomal fractions were prepared from heart muscle excised from foetal guinea pigs and rabbits 1 day before their anticipated date of birth, and from 1 day old and adult animals. For control purposes microsomes were also prepared from the relevant maternal stock animals. One day before birth the cardiac microsomes of the foetal but not of the maternal animals exhibited a decreased ability to accumulate Ca2+ by uptake but not by the binding process, and a decreased ability to hydrolyse ATP. This reduction in ATPase activity involved both the Ca2+-dependent and the Ca2+-independent ATPase enzymes. One day after birth the Ca2+-accumulating activity of the neonatal microsomes had increased, that of the rabbit via an increase in Ca2+ uptake and that of the guinea pig by an increase in Ca2+ binding. These changes were accompanied by an increase in the activity of the Ca2+-dependent ATPase. The results are interpreted to mean that the cardiac SR changes at about the time of birth, and that although the pattern of these changes may be species specific they result in an increase in the Ca2+-accumulating activity of the SR.


Reduced myocardial actomyosin adenosine triphosphatase activity in the ageing male Fischer rat.

Actomyosin was extracted from myocardial homogenates from male rats of different ages of a long-inbred Fischer rat colony maintained under controlled conditions of temperature, humidity, and light. ATPase specific activity rose to a maximum at 2 months of age; this was followed by a progressive decline by about 25% at 16 months of age. However, the extractable actomyosin remained constant during this period. This loss in actomyosin ATPase specific activity is in good agreement with previously reported decrements in both stroke index and myocardial calcium content and an increase in myocardial contraction duration in aged rats.


National randomized study of chemotherapeutic agents in advanced prostatic carcinoma: a progress report.

In the 36 months since its inception, the National Prostatic Cancer Project treatment subgroup has randomly assigned over 360 patients with progressive advanced prostatic cancer who were no longer responsive to endocrine manipulation to either one of four different clinical studies. The initial study demonstrated a clear superiority for 5-fluorouracil (5-FU) and cyclophosphamide over continued conventional therapy. Beneficial responses were documented and are associated with increased survival rates and relief from pain and other symptoms. A proportionately larger number of patients obtained clinical benefit (stable and partial regression) on cyclophosphamide than on standard or 5-FU therapy. The criteria for evaluation of patients are supported by the survival data, ie, responders have survived for a longer period of time than those patients who continued in progression. Preliminary data from the subsequent protocols have documented a 30% response (stable and partial regression) in patients receiving oral estramustine phosphate and definite responses in patients treated with DTIC; Too few patients have been treated with Leo 1031 to offer total response rates at this time, although the early results are promising. These clinical studies have firmly established a place for chemotherapy in the management of prostatic cancer. New trials will introduce single- and multiple-drug chemotherapy at earlier phases of the clinical course of prostatic cancer patients.


Amino acid transport in the rat exocrine pancreas. II. Inhibition by lanthanum and tetracaine.

The two calcium antagonistic agents lanthanum and tetracaine cause severe disturbances in the secretory process of the exocrine pancreas, including inhibition of the rate of protein synthesis and exocytosis. The former effect resulted mainly from the inhibition of amino acid transport. Lanthanum in a concentration up to 1 mM inhibited transport of different species of amino acids in an unspecific way whereas tetracaine interfered specifically with the Na+ -dependent transport system for neutral amino acids (14C-alpha-amino-isobutyric acid). Na+ -dependent transport of neutral amino acids (3H-leucine) was not affected. Transport inhibition was correlated to the acitvity of the Na+, K+ -ATPase system which was measured in isolated plasma membrane fractions. At higher concentrations (5-10 mM) some uptake of lanthanum into the cells by limited endocytosis was observed. At lower concentrations lanthanum seemed to bind exclusively to certain components of the plasms membrane, mainly at the lateral and basal cell surface. Even at a concentration of 5-10 mM no binding to the apical surface occurred. Similarly no binding of lanthanum was observed to the limiting membrane of isolated zymogen granules, while mitochondria, contained in the same fraction showed considerable binding affinity. The action of lanthanum and  tetracaine on membrane carrier systems did not affect the interior organization of the plasma membrane. Particle density and distribution in freeze-fracture replicas as well as the submembrane microfilamentous=microtubular system and the junctional elements remained unaffected.


Differentiation of slow and fast muscles in chickens.

1. The development of the characteristic histochemical appearance of the slow anterior latissimus dorsi (ALD) and fast posterior latissimus dorsi (PLD) was studied in chickens during embryonic development as well as during regeneration of minced muscle. 2. During embryonic development the activity of the oxidative enzyme succinic dehydrogenase (SDH) is higher in the slow ALD muscle already at 16 days of incubation. At this time the fast PLD has a higher activity of the glycolytic enzyme, phosphorylase. Although the histochemical appearance of the two types of muscle is already different at 16 days, their contractile speeds are still similar. No difference in myosin ATP-ase was found in the two muscles in young embryos but in 20-day old embryos the two muscles became distinctly different when stained for this enzyme. 3. When PLD muscles in hatched chickens redeveloped during regeneration in place of ALD the histochemical characteristics of the regenerated muscle resembled ALD, and when ALD regenerated in place of PLD it resembled PLD. 4. It is concluded that the histochemical characteristics of slow and fast muscles become determined during early development, even before any difference in contractile properties can be detected and that they are determined by the nerve.


Ultrastructural studies on the Malpighian tubule of the pill millipede, Glomeris marginata (villers).

Ultrastructural studies on the Malpighian tubules of Glomeris marginata (Villers) reveal considerable morphological differences between the upper, fluid secreting, segment, and the lower segment which is at present of unknown function. Previous reports have shown that the upper tubule has a high permeability to compounds of high molecular weight. This may be accounted for by the fact that the epithelium shows very extensive intercellular spaces which are linked directly to junctions apparently specialised to provide a low resistance extracellular pathway between the haemocoel and the tubule lumen. Histochemical studies on the localisation of phosphatase enzymes reveal intracellular vesicles with acid phosphatase activity. The basal labyrinth of the lower tubule exhibits considerable alkaline phosphatase activity which is apparently identical in location to the enzyme revealed by two different ATPase localisation techniques.


Calusterone therapy for advanced breast cancer.

Calusterone was given at a dose of 200 mg daily to 45 postmenopausal patients with advanced metastatic breast cancer. Of the 40 evaluable patients, 11 were unable to tolerate the drug because of severe toxicity. Objective regression of soft tissue disease and relief of bone pain were seen in four patients (9.1%) for an average duration of 15.2 weeks. Thirteen patients showed an arrest of disease progression. In 12 patients the lesions continued to progress in spite of therapy. Toxic effects consisting of nausea, vomiting, fluid retention, SGOT elevation, and androgenic side effects were seen in 33 patients (75%), necessitating discontinuation of the drug in 11 (25%).


Left ventricular endomyocardial biopsy. III: ultrastructural characteristics of cardiomyopathy and cardiac hypertrophy with good or poor ventricular function.

Left ventricular endomyocardial biopsies have been obtained from patients with cardiomyopathy and hypertrophy due to aortic valve disease. These biopsies have been examined by electron microscopy and the ultrastructural abnormalities compared. In congestive cardiomyopathy no specific abnormalities were found although myofibrillary degeneration and membrane-bound vacuoles were more commonly present. Crossing of whole groups of sarcomeres was found only in asymmetric septal hypertrophy, but was not present in all cases. Amyloid deposits were demonstrated easily by electron microscopy in patients with restrictive cardiomyopathy. In the patients with hypertrophy due to aortic valve disease, no specific features were found and ultrastructural abnormalities did not differentiate between normal and impaired left ventricular functions.


Asymmetric septal hypertrophy and myocardial fiber disarray. Features of normal, developing, and malformed hearts.

The specificity and significance of the asymmetric septal hypertrophy (ASH) and myocardial fiber disarray of idiopathic hypertrophic subaortic stenosis (IHSS) is uncertain. To examine this we studied 215 hearts, including normal embryos, fetuses, children, and adults; and hearts with congenital and acquired disease. Disproportionate septal thickening was present in all embryos and in some abnormal hearts, particularly those with severe right ventricular hypertrophy due to congenital malformations. Some myocardial fiber disarray was present in all hearts at the junctions of interventricular septum and ventricular free wall. In hearts with semilunar valve atresia with intact ventricular septums, and in the infundibulum of some with tetralogy of Fallot, however, extensive fiber disarray was present. Thus, ASH occurs in the normal developing heart and in some malformed hearts with RVH; marked muscle fiber disarray may occur in certain congenital lesions with abnormal systolic contraction. Neither morphologic finding independently or in combination is pathognomonic of idiopathic hypertrophic subaortic stenosis.


An experimental resource centre on handicap in children. 1. Preliminary analysis of need for such a centre.

An experimental information and resource centre on handicap in children for the use of staff in the health, social and educational services was set up in an area of London serving four adjacent boroughs. As a first step, a questionnaire was widely distributed to potential users  of the centre asking for information about their work, training and recent reading in this subject. Of 192 replies, those from health visitors, medical officiers, teachers and therapists are analysed. Lack of adequate training, both at basic and post-qualification level, as well as a failure to keep up to date with specialized journals, encouraged the establishment of the resource centre, which also planned to provide a course of lectures and seminars. The nature of the material collected is briefly described.


Echocardiographic evaluation of fixed left ventricular outlet obstruction in children. Pre and postoperative outlet obstruction in children.

Rencently, several investigators have utilized the echographically determined magnitude of relative left ventricular posterior wall hypertrophy as a reflection of normalized systolic wall stress to estimate left ventricular systolic pressure noninvasively. In this study, relative wall thickness determined echographically was compared to peak systolic pressure measured at catheterization in 20 children without obstruction to left ventricular outflow and with normal left ventricular function. From these data a relationship, pressure = 225 X left ventricular systolic wall thickness/left ventricular end-systolic internal dimension, was derived. The relationship was then applied to 57 children with fixed aortic stenosis. Left ventricular pressure estimated echographically compared well with that demonstrated at cardiac catheterization (r = 0.89). Twenty-one patients had further echographic studies following surgical relief of outlet obstruction. Estimated left ventricular pressure fell to normal values within two months following surgery in over half the patients with good surgical relief of obstruction, and was normal at subsequent studies up to 22 months postoperatively in all but one patient with good surgical relief. In patients in whom outlet obstruction was not adequately relieved at surgery, echographically estimated left ventricular pressure remained persistently elevated.


An experimental resource centre on handicap in children. 2. Results from one year's operation.

An experimental resource centre on handicap for professional workers in four London boroughs as well advertised through all the relevant social, health and education departments. It provided a wide range of reference and display material as well as a programme of 20 lectures from experts with different backgrounds. The response to the centre by the various professions is reported, both in respect of visits to use its resources and of attendance at seminars and lectures. The response was disappointing, particularly from social workers and teachers. The centre had to close from lack of support after one year. Possible causes for the lack of response are discussed, and suggestions are made as to how the quality of the service given to handicapped children and their families can be improved.


The Priory Parents Workshop.

The workshop was a successful attempt to to meet the needs of parents of handicapped children. Using a multidisciplinary team the 16-session workshop enabled both parents and professionals to discuss the problems associated with handicapped children and possible practical solutions. The unique approach of the Priory Workshop could be the prototype for future community services to help the mentally hanidcapped.


Mixed lymphocyte reaction and graft survival in forty cadaveric renal transplants.

The value of the MLR in predicting graft outcome was evaluated in forty cadaveric grafts. The MLR was assessed by the one and two way stimulation index (SI), the relative response (RR), and the stabilized relative response (SRR). Graft function was assessed by function at 3 and 6 months after transplantation, and a rejection grading based on the number and severity of rejection episodes during the first 3 months after transplantation. No correlation was found between the MLR and graft outcome in these patients.


Differential effect of pregnancy or gestagens on humoral and cell-mediated immunity.

The reactivity of spleen lymphocytes in a mixed lymphocyte culture and the in vivo PFC response to sheep erythrocytes have been evaluated in pregnant female mice and data compared with those observed in virgin sexually mature female mice daily treated either with progesterone or human chorionic gonadotropin (HCG) or human prolactin. The mixed lymphocyte reactivity is depressed at mid-pregnancy, whereas PFC response is increased. Comparable immunological modifications have been found in mice treated with HCG, but not in animals treated with progesterone or prolactin. The similarity between HCG treatment and pregnancy suggests that the rate of gonadotropin release may be one of the earliest events responsible for the immunological disturbances present during pregnancy, although its action on the lymphoid system seems to require the presence of the ovary. From these data and from the observation that HCG increases the PFC response also in thymusless nude female mice, it can be deduced that it acts on both T and B cells.


Differential effect of pancreatectomy on humoral and cell-mediated immune responses.

Cell-mediated immune reactions, such as allogenic skin-graft rejection and PHA or MLC responses, and antibody synthesis against different antigens (sheep erythrocytes, Brucella antigen, bovine serum albumin) have been evaluated in rats suffering from experimentally-induced diabetes and in age-matched sham-treated controls. Cell-mediated immune reactions are strongly depressed diabetic rats. The cellularity of the thymus and of thymus-dependent areas and the number of peripheral blood lymphocytes is significantly reduced in pancreatectomized rats. Moreover, the immunological recovery from heavy cortisonization is also greatly impaired. Daily treatment with insulin may prevent these immunological alterations. By contrast, antibody responses in diabetic rats are not quantitatively altered in respect to either the number of antibody producing cells in the spleen or the circulating antibody titres. The discrepancy between the abnormality of cell-mediated immune reactions in diabetic rats and their physiological capacity to synthetize antibodies suggests that the sensitivity to an insulin-deprived environment is present only in a definite, although yet undefined, subpopulation of  lymphoid cells rather than in the whole lymphoid system.


Analytical subcellular fractionation of guinea-pig myocardium.

1. Homogenates of guinea-pig left ventricle were fractionated by differential pelleting and by centrifugation on continuous sucrose density gradients. 2. The principal subcellular organelles of myocardium, characterized by their marker enzyme content, were resolved by density gradient centrifugation in a small-volume zonal rotor. The equilibrium densities (p) of the principal organelles are (with marker enzymes in parentheses): sarcolemma, 1-12 (5'-nucleotidase); lysosomes, 1-16 (N-acetyl-beta-glucosaminidase); mitochondria, 1-17 (cytochrome oxidase); peroxisomes, 1-18 (catalase); cytosol (lactate dehydrogenase). 3. The subcellular distribution of various adenosine triphosphatase activities and previously unassigned enzymes was determined. Leucyl-beta-naphthylamidase and gamma-glutamyl transpeptidase showed both cytosol and sarcolemma components. Ca2+-dependent adenosine triphosphatase showed dual localization to the mitochondria and to the sarcolemma.


Intramuscular gold for rheumatoid arthritis.

Improvement from gold therapy is not immediate but comes about very slowly. The patient and physician should be forewarned that as many as 8 to 14 weeks may pass before any benefit is noted, and that months of treatment may be required before improvement is sufficient to decrease disability. With effective therapy, signs of inflammation gradually decrease, pain abates, and function improves. Not all patients benefit, and whether beneficial results occur can be determined only by clinical trial. There is no advance method of determining whether treatment will be effective. Gold therapy suppresses rheumatoid inflammation and checks the progress of the disease. It should not be used alone, but shoud be part of a well-planned program of treatment carefully adjusted to the needs of the individual. This therapy will include steroidal and nonsteroidal anti-inflammatory agents (including aspirin), which should not be reduced or abandoned until definite improvement from gold can be determined. With the possible exception of palindromic and juvenile forms, RA is the only rheumatic disease benefited by intramuscular gold therapy. The treatment should never be used for  other forms of rheumatism.


Irritant dermatitis during the relining of a blast furnace.

An outbreak of dermatitis is reported amongst steel erectors, platers and welders working on the relining of a blast furnace. Evidence is produced for regarding this as an occupational primary irritant contact dermatitis.


The role of sulphation of glycosaminoglycans in their structural and functional characteristics.

The CD spectra in the far ultraviolet and the CD and ORD spectra of methylene blue-complexes (MB-complex) of glycosaminoglycans (GAG) with different sulphate contents were studied in comparison with their effect on the in vitro formation of collagen fibres. The following polyanions were investigated: Chondroitin sulphate-A with different sulphate contents, oversulphated chondroitin sulphate, heparin and dextran sulphate and their desulphated derivatives. It was observed that the MB-complex of polysaccharides with the same backbone structure, but with different sulphate contents might show ORD and CD spectra of exciton type, but of inverse sign. This phenomenon was interpreted on the basis of different types of aggregation of dye molecules bound to the polysaccharides. The biological effect of GAG changed also with the sulphate content. This suggests that it is the extent of sulphation rather than the glycosidic structure of GAG which determines their chiroptical and functional properties.


Collagen cross-linking alterations in joint contractures: changes in the reducible cross-links in periarticular connective tissue collagen after nine weeks of immobilization.

A significant increase in the NaBH4 reducible intermolecular cross-links in the 9 week immobilized rabbit periarticular connective tissue was found. Dihydroxylysinonorleucine, hydroxylysinonorleucine, and histidinohydroxymerodesmosine were the major cross-links which increased during the period of immobilization. No change in the hydroxlysine/lysine ratio between the immobilized and control periarticular connective tissue collagen was detected during the 9 weeks of enforced immobilization of the rabbit knee. Since the collagen mass in the immobilized periarticular connective tissue does not change, or at most is reduced 10%, we suggest that there is an increase in collagen cross-links expressed both in per unit weight of collagen and on the basis of collagen mass per knee due to the lack of physical stress and motion.


Interaction between collagen type I and type III in conditioning bundles organization.

Type I and type III collagen extracted from skin was purified by differential salt precipitation and chromatography. By heating to 37 degrees, type I formed after a lag phase a floppy and opalescent gel of high optical density and type III formed more rapidly a translucent and rigid gel of low optical density. Addition of type III to type I resulted in formation of gels of reduced optical density and lag phase related to the proportion of type III added. Phase contrast and scanning electronmicroscopy demonstrated the formation of thick bundles of type I, thin fibers of type III and bundles of intermediate size related to the proportion of type III. The relationship between collagen type and bundle architecture might prove most significant in conditioning the mechanical properties of the connective tissues in normal and pathological conditions.


X-ray diffraction and scanning electron microscopy of bovine media aortic wall.

Scanning electron microscopy and high angle X-ray diffraction were used to define the relationship between collagen and elastin of bovine aortic wall. The diffraction pattern shows on one hand that the broad rings at 4.5 A and 9 A, due to elastin, do not orient on stretching and on the other hand, that the collagen rings at 11 A and 2.9 A start to orient at low elongations. These data together with scanning electron microscopy suggest a tight structural relationship between collagen and elastin that should influence the mechanics of deformation at all degrees of elongation.


Histological and biochemical studies on cartilage from osteoarthrotic femoral heads with special reference to surface characteristics.

A study has been made of cartilage from osteoarthrotic femoral heads in an attempt to relate histological to biochemical and metabolic changes. Cartilage showing different surface characteristics and originating from different areas of the femoral head has been studied. Depending on its surface characteristic and location, the osteoarthrotic cartilage ranged in composition and sulphate metabolism from practically normal to glycosaminoglycan depleted and metabolically depressed. There was no indication of elevation in the sulphate incorporation in the osteoarthrotic cartilage.


Osteogenesis imperfecta: morphological, histochemical and biochemical aspects. Modifications induced by (+)-catechin.

Two patients affected with two different forms of Osteogenesis Imperfecta were examined in order to study collagen and glycosaminoglycans (GAGs) in skin and iliac crest cartilage. A sharp decrease of the galactosamine to glucosamine ratio due to a reduced content of chondroitin sulfate was evidenced in both patients. Moreover the structure of proteoglycans appeared altered, this being more evident in the severe form of the disease. Morphological examination in light and electron microscopy of cartilage of the less severely diseased patient showed that GAGs in the extracellular matrix did not present regular connection with collagen fibers. Chondrocytes, elongated and disorderly scattered, showed large lipidic inclusions and, on histochemical basis, were devoid of UDPG dehydrogenase activity. Treatment with (+)-catechin produced an improvement, in both patients, of the biochemical pattern of collagen and GAGs. Similarly a shift of the cellular activity and of the matrix morphology towards normality was observed in the investigated cartilage of the less severely affected patient.


Characterisation of the major collagen species present in porcine aortae and the synthesis of their precursors by smooth muscle cells in culture.

Porcine aortae were digested with pepsin and the solubilised collagen molecules separated by differential salt precipitation at pH7.5. The fraction precipitated at 1.71 M NaCl was shown to comprise collagen type III as judged by its elution characteristics from CM-cellulose, its alpha-chain composition on sodium dodeclysulphate polyacrylamide gel electrophoresis, and amino acid analyses. Pepsin-derived type I collagen was recovered by precipitation at 2.56 M NaCl and similarly characterised. cultures of porcine arterial smooth muscle cells have been established and radiolabelling studies with [14Clproline have demonstrated that these cells synthesis and secrete the precursors of collagen types I and III into the culture medium. Ion-exchange chromatography of these secreted collagen molecules and gel filtration of their pepsin-derived alpha-chains have demonstrated that type III is the major collagen species present in the medium.


Old drug--in a new system--revisited.

Sodium sulfacetamide, penetrating antibacterial, in combination with hydrocortisone and sulfur, has enjoyed twenty years of remarkable safety, with outstanding efficacy and patient acceptance, in the prescription treatment of pustular acne and severe, refractory seborrheic dermatitis. Recently, this combination has been reported to be highly effective concomitant therapy for perioral dermatitis. Almost paradoxically, it achieves these desired goals without the excessive erythema and discomforting irritation associated with retinoic acid and benzoyl peroxide.


Adverse effects of right ventricular pacing in a patient with aortic stenosis, Hemodynamic documentation and management.

A patient with moderate aortic stenosis, left ventricular hypertrophy, and a permanent right ventricular pacemaker for a sick sinus node presented with hypotension, dizziness, and angina pectoris with paced beats. The hemodynamics of pacing were documented with non-invasive and invasive studies. The patient was successfully treated with a programmable generator and pacing at a lower rate. The neccessity of evaluating the effects of a temporary pacemaker before insertion of a permanent one and of a reevaluation of the hemodynamic status in the presence of unexplained cardiac failure in a patient with permanent pacemaker are emphasized in this case report.


Electrode causation of pacemaker inhibition.

Electromechanical nonphysiologic signals caused by the movement of intracardiac metal portions of an endocardial grasping electrode were shown to be "falsely" recycling an implanted pacemaker. The signals were similar in amplitude and slew rate to the ventricular electrogram and were terminated by ending the movement of the two metallic surfaces.


Recurrent tachyarrhythmia associated with a bifocal demand pacemaker.

A recurrent tachyarrhythmia complicated the course of a patient with a permanent atrioventricular sequential (bifocal) demand pacemaker. Investigation by intracardiac electrocardiographic studies revealed that the arrhythmia was associated with normally functioning bifocal pacemaker, whose atrioventricular sequential interval approximated the patient's conduction time from atrium to ventricle. The mechanism of initiation and conversion of the arrhythmia was elucidated. Appreciation of this arrhythmia is necessary for appropriate clinical use of a bifocal demand pacemaker.


[Combination chemotherapy and cranial irradiation in 530 children with acute lymphoblastic leukaemia (author's transl)].

530 children with acute lymphoblastic leukaemia were diagnosed between 1. 1. 1971 and 31. 12. 1974, and treated at 35 German hospitals according to the Memphis study VII or VIII2 and subsequently followed until 31. 12. 1976. At diagnosis 17.2% of the patients had a WBC count of over 50,000/mm3, 8.9% had mediastinal enlargement, 2.1% CNS leukaemia and 1.7% Down's syndrome. After being treated for two and a half years and being observed for a maximum of six years (minimum two years) 262 children (49.4%) were living, 203 (38.8%) in continued complete remission, most of them one to three years after end of treatment. Primary bone marrow relapse occurred in 39.6%, but CNS relapse in only 8.7%. Cranial irradiation at a dose of 1800 rad in 70 patients produced a CNS relapse of only 7.1%. Forty-one of these 530 children (7.7%) died in continued complete remission, the main causes being interstitial pneumonia and varicella. There was no difference in initial features and treatment results between six centres which had many and 29 with rather fewer patients. The five-years-survival rate (life-table method) was 41 +/- 3.5% for all 530 children and 10 +/- 3.7% for the 92 children with initial leucocyte counts of over 50.000/mm3.


The importance of serologically detectable histocompatibility antigens in the induction and effector step of cell-mediated lysis.

The induction and effector steps of T cell-mediated cytotoxicity (CMC) have been studied using a mouse tumor cell line and its variant, which is deficient in serologically defined (SD) H-2 antigens. In allogeneic mice the SDxcell line induces CMC, while the SD- cell line does not. However, both cell lines can be lysed by xenogeneic rat lymphocytes. Antiserum specific for rat T cells was used to demonstrate that CMC of both targetss is partially due to T cells. In allogeneic or syngeneic mouse systems the SD- cells coupled with the 2,4,6-trinitrophenyl (TNP) residue can neither induce CMC nor serve as targets for CMC, while TNP-coupled SDxcells can serve both as immunogen and as targets. Thus allogeneic or syngeneic mouse T cells do not interact with the TNP group of targets lacking H-2 SD antigens. However, mouse T killer cells sensitized to TNP-coupled cells may lyse TNP-coupled targets carrying different H-2 haplotypes. These experiments show that the induction and effector steps of CMC executed by mouse T cells, using TNP-coupled cells as immunogen or targets, need not necessarily demonstrate restriction with regard to a certain genetically defined H-2 haplotype. The presence of cell surface H-2 SD antigens is however, absolutely necessary for the induction and effector steps of CMC by mouse T cells. Using cold target inhibition assays, it was not possible to demonstrate recognition of the TNP moiety on TNP-coupled SDxcells.


[3H]-ouabain binding to denervated and innervated skeletal muscle.

In cat skeletal muscles, the major part of specific [3H]-ouabain binding was found in the sympathetic nerve endings of red, slow muscle fibres. Skeletal muscle denervation increased specific [3H]-ouabain binding to muscle membrane preparation. This increase may be involved in the development of spontaneous fibrillation in the denervated muscle.


Stimulation of cardiac sarcolemmal (Na+--K+) ATPase activity by phosphorylase kinase.

Following preincubation with phosphorylase kinase, ATPase activities of heart sarcolemmal membranes were increased: total ATPase from 9.38+/-0.65 to 15.25+/-0.90 and ouabain-sensitive (Na+--K+)ATPase from 1.67+/-0.17 to 3.12+/-0.33 micron moles Pi/mg protein/h (mean +/- S.E. of 3 experiments); (Ca2+)ATPase and (Mg2+--Ca2+)-ATPase activities were not significantly altered due to phosphorylase kinase. Under these conditions, phosphorylase kinase catalyzed phosphorylation of sarcolemmal membranes. The kinase-catalyzed phosphorylation of membranes was increased by Ca2+ ions: at pH 6.8, 30% increase in phosphorylation was observed whereas at pH 8.5, 267% increase was noted due to this action. These findings support the view that Ca2+-dependent phosphorylation of membranes regulates (Na+--K+)ATPase.


Recent advances in the immunological aspects of renal disease.

Anti-basement membrane antibodies and tissue deposition of immune complexes appear to be responsible for most glomerulonephritides and for some tubulo-interstitium injury accompanying glomerulonephritis or occuring primarily. Anti-tubular basement membrane antibodies complicate immunologic and toxic renal injury, including transplantation, and widespread tubulo-intersitial immune complex deposits are present in most patients with systemic immune complex disease, such as lupus erythematosus. Radioimmunoassay is now available for detecting and monitoring circulating anti-glomerular basement membrane antibodies. The effect of aggressive therapy with immunosuppression and plasma exchange is being studied to determine is value in minimizing tissue damage produced by the usual transient production of anti-glomerular basement membrane antibodies. Techniques are being explored to detect circulating immune complexes. Vigorous efforts are under way to identify antigen-antibody systems involved in the production of nephritogenic immune complexes, which may lead to antigen irradiation or specific manipulation of the immune response or its products.


Contractile proteins in phagocytosis: an example of cell surface-to-cytoplasm communication.

Phagocytosis is a prime example of a cellular event in which cell surface perturbation activates the assembly of a filamentous gel beneath the plasma membrane. This gel may be responsible for movement of the membrane around ingestible particles. The molecular mechanism of these events is being approached by the purification of actin, myosin and associated proteins from phagocytic cells and by the study of a human disease, neutrophil actin dysfunction. Novel contractile proteins discovered in mammalian phagocytes include a cofactor that regulates actin:myosin interaction and an actin-binding protein that promotes assembly and gelation of actin. There is evidence that phagocytosis alters the state of the actin-binding protein, and that this alteration may be an early event in the assembly of the actin gel. Cytochalasin B, which inhibits phagocytosis, acts by interfering with the interaction between actin-binding protein and actin. Actin polymerized poorly in the neutrophils of a human infant, and the affected neutrophils were deficient in phagocytosis. Actin assembly is important in phagocytosis and is amenable to biochemical analysis.


Problems with tubal reconstruction following laparoscopic sterilization using the electrocoagulation and resection technique.

This paper reviews the results of attempted tubal reconstruction following laparoscopic sterilizations using the electrocoagulation and excision technique in the isthmic portion of the fallopian tube. The surgical technique, complications, and results are presented.


Dermatologic investigation of betamethasone 17,21-dipropionate ointment with chinoform.

In an open investigation on 50 patients with various dermatological lesions 17 (81%) out of 21 psoriatics and 28 out of 29 other patients inproved considerably or were clinically cured after three weeks' treatment with an ointment containing 0-05% betamethasone dipropionate and 3-0% chinoform. Among the patients chosen for the study 34 had previously tried topical corticosteroids without success. Of these 31 improved markedly during the steroid trial.


Peripheral nerve fiber size in experimental diabetes.

Serial morphometric observations were made on the tibial nerves of mature rats before and five weeks after the induction of diabetes by streptozotocin. Maximum and average myelinated fiber diameter did alter, neither did the relationship between myelin sheath thickness and axon circumference. This confirms previous observations suggesting that the reduced nerve conduction velocity that is known to occur in experimental diabetes is likely to depend on metabolic alterations rather than on structural changes.


Successful intra-splenic transplantation of syngeneic and allogeneic isolated pancreatic islets.

Adult rat islets harvested by the collagenase digestion/Ficoll separation technique were injected into the splenic pulp in 9 syngeneic (Lewis-leads to Lewis and WaG leads to WaG) and 13 allogeneic [(DA X Lewis) F1 leads to Lewis] experiments. Normal serum glucose levels and 24 hour urine volumes were restored in all 9 syngeneic recipients and in 11 out of the 13 allogeneic recipients in a mean of 3.3 days. Splenectomy performed on 3 of the 9 syngeneic recipients 110-178 days after transplantation resulted in a prompt return to the diabetic state. In all the remaining syngeneic recipients, normal values have persisted for the current period of observation of 6 months. In 5 untreated allogeneic recipients, rejection occurred in a mean of 5.2 days. The administration of a short course of ALS (1 ml I.P. days-1, 1, 3 and 5) to the remaining 6 animals greatly prolonged graft survival with all animals remaining normoglycaemic for at lest 4 weeks. These results were not significantly different from those recorded in comparable groups of intra-portal allogeneic islet recipients.


NaK-ATPase in rat pancreatic islets.

Shifts in the distribution of the monovalent cations Na+ and K+ between the extra- and intracellular space seem to be important for the secretory response of the beta-cell. An attempt was therefore made to study the enzyme responsible for monovalent cation transport, the (NaK)-activated ATPase. In the presence of NaN3 as inhibitor of the mitochondrial Mg-ATPase, a NaK-ATPase with a specific activity of 72 mU X mg protein-1 could be demonstrated in crude membrane preparations of rat pancreatic islets. The enzyme, which was inactive in the absence of Mg++, needed both Na+ and K+ for activation and was inhibited by ouabain and PCMB. The main part of the NaK-ATPase was localized in the microsomal fraction. Glucose, sulphonylureas, somatostatin and diazoxide were without effect on NaK-ATPase.


["Idiopathic" chronic paralysis and dilatation of the right atrium].

Electric and mechanical atrial paralysis is a condition usually associated with a primitive or secondary cardiopathy. Only extremely rare cases are characterized by early appearance in young subjects without evidence of cardiac disease of any kind whatever, without character of familiarity, with atrial paralysis being the only abnormality, and are thus defined as idiopathic atrial paralysis. One of these cases (the eighth in the literature, to our knowledge), presented with a complete study and the hypothesis that "chronic idiopathic atrial paralysis" and "idiopathic right atrial enlargement"  (sometimes associated, as in this case) may be different manifestations of the same chronic myocardial disease.


Effects of insulin and NSILA on adipocytes of normal and diabetic rats: receptor binding, glucose transport and glucose metabolism.

Isolated fat cells from normal and streptozotocin-diabetic rats were compared with respect to metabolic indices (glucose-uptake, 3-0-methyl-glucose efflux) with and without stimulation by insulin and nonsuppressible insulin-like activity (NSI-LA). In addition, binding studies were carried out with these two hormones. Basal 14C-glucose oxidation and incorporation into lipids was decreased in diabetic cells and their response to insulin and NSILA was greatly reduced. Basal efflux of 3-0-methylglucose from diabetic cells was somewhat faster than from normal cells. The response to insulin and NSILA was less than in normal cells and it was delayed. The apparent number of insulin binding sites as well as their affinity for insulin was increased in diabetic cells. In contrast, the apparent number of binding sites for NSILA was decreased in diabetic cells and their affinity for NSILA was increased. In normal cells insulin enhanced binding of 125I-NSILA more markedly than in diabetic cells. These findings show that the rate-limiting step of impaired glucose metabolism (oxidation and lipogenesis) in diabetic fat cells is beyond the interaction of the hormone with the receptor. They suggest that the apparent number of hormone receptors (insulin, NSILA) on the cell membrane is regulated individually for each binding site.


[Isolated mitral stenosis: systolic and diastolic dynamic geometry of the left ventricle. Integration with several hemodynamic parametres (author's transl)].

75 patients with isolated mitral stenosis were studied. Particular attention was paid to the integration of the parametres VTD, FE, mitral area, pulmonary artery pressure and dynamic systolic and diastolic geometry of the left ventricle. The existence of isolated MS with alteration of the left ventricular function not depending on the alterations of the preload and the forms with raised FE, was demonstrated. A classification into 6 groups was made, each characterized by special geometric modalities of contraction and relaxation. A significant compensation of several of the parametres of systolic mecanism (hyperkinesia) and diastolic (SERP) dynamic geometry was observed. It was therefore concluded that a more precise definition of the interaction of ventricular function with left atrial function is necessary.


[Results of animal experiments on alloplastic tendon replacements using the Bader tendon prosthesis].

Based on our experimental results with the Bader tendon prosthesis, encouraging results for alloplastic tendon replacement were obtained. However a general recommendation for its clinical use cannot be given. Over a period of 4-6 weeks of immobilization healing of the artificial tendon with inflammation could be observed. In the biopsies we found the equivalent of connective tissue attachment between vital tissue and the alloplastic material. We could not clarify whether this connection would endure strain. The pronounced adhesions between the anstomosis and surrounding tissue make later function questionable.


[The effects of dantrolene sodium on the nervous system (author's transl)].

In order to investigate the effects of Dantrolene sodium on the nervous system, the experiments were carried out on cats. 1. Group Ia spindle afferent discharges were suppressed in 6 out of 14 cases following application of the drug. The effect lasted for 20 to 90 minutes. 2. No significant effects were observed on spinal mono- and polysynaptic reflexes, nor was seen on interneurons. However, 3 out of 9 Renshaw cells were facilitated and 3 were inhibited after Dantrolene sodium application. 3. Alternating discharges in the ventral root filaments, evoked by stimulation of N. cuneiformis, were suppressed by the drug application.


Progressive restriction of antigen binding by human foetal thymus lymphocytes.

The proportion of foetal thymus lymphocytes (FTL) that binds the bacterial antigens beta-galactosidase and flagellin is high in early foetal life. Binding of beta-galactosidase, and the response by FTL in mixed lymphocyte culture falls during gestation. Some FTL bound both antigens, suggesting that immature lymphocytes are not fully restricted in their capacity to recognize antigens. Such findings have been reported in foetal lymphocytes from other species. We suggest that cellular diversity may partly be generated by progressive restriction of antigen recognition by individual lymphocytes, which may result from progressive stabilization of genetic repression during lymphocyte multiplication.


Blastogenic factors: production by T and B lymphocytes. Effect on T and B cells.

The aim of the present report is to identify the cells responsible for the in vitro production of blastogenic factor and to evaluate the effect of blastogenic factor on T and B lymphocytes. Human T lymphocytes were purified by a nylon wool column filtration method and B-cell-enriched populations were purified by sedimentation of E rosettes on Ficoll-Hypaque. The results were summarized as follows: Both T cells and B cells can produce blastogenic factor. However, blastogenic factor produced by T cells differed in some respects from blastogenic factor produced by B cells. (a) Blastogenic factor produced in unmixed B-cell cultures stimulated both B cells and T cells to proliferate, whereas blastogenic factor produced in unmixed T-cell cultures stimulated only B cells. (b) The production of T-cell blastogenic factor was accelerated when stimulated by allogeneic cells. In contrast, the blastogenic activity of supernatants from mixed cultures of B cells was not different from that of supernatants from unmixed cultures. The significance of these findings for mixed leucocyte reaction is discussed.


Experiments on lymphocyte-mediated cellular immunity in murine histoplasmosis.

Peritoneal exudate cells from immunized mice inhibit the intracellular growth of Histoplasma capsulatum. The lymphocyte is the mediator cell of this phenomenon. Lymphocytes from immunized animals are highly activated cells. Supernatants from cultures of immune lymphocytes or from cultures of mitogen-stimulated lymphocytes did not arm macrophages from normal animals to inhibit the intracellular growth of H. capsulatum.


Differential chemical protection of mammalian cells from the exotoxins of Corynebacterium diphtheriae and Pseudomonas aeruginosa.

Many drugs or chemicals had markedly different effects on the cytotoxicity induced by Pseudomonas aeruginosa exotoxin A (PE) or Corynebacterium diphtheriae exotoxin (DE). The glycolytic inhibitor NaF protected cells from DE but potentiated the cytotoxicity of PE. Another energy inhibitor, salicylic acid, also protected cells from DE but had no effect with PE. Colchicine and colcemid did not affect the cytotoxicity of either toxin. Cytochalasin B exhibited a modest protection from DE but no effect with PE. Ouabain, a specific inhibitor of the Na+, K+-dependent adenosine 5'-triphosphatase (ATPase), did not affect the cytotoxicity of either toxin. Ruthenium red, a specific inhibitor of the Ca2+, Mg2+,-dependent ATPase, conferred marked protection from DE-induced cytotoxicity but did not affect PE-induced cytotoxicity. A number of local anesthetics were tested, and they too presented differential results with PE and DE. Most chemicals that affected toxin-induced cytotoxicity had little or no influence on the in vitro adenosine 5'-diphosphate-ribosylation catalyzed by either toxin. This work presents further evidence that PE and DE have different mechanisms of intoxication and suggests that these differences lie in the attachment or internalization stages of intoxication.


An update on acne vulgaris.

Seven important therapeutic measures in managing acne are described, for the treatment of the 7 types of acne. These therapeutic measures are retinoic acid, benzoyl peroxide gel, topical antibiotics, oral antibiotics, intralesional corticosteroids, liquid nitrogen and oral corticosteroids.


Cataractogenic effects of a boron hydride disulfide compound.

The disulfide form but not the sulfhydryl form of a boron hydride compound was found to be cataractogenic. Apparently this compound attaches to the sulfhydryl group of Na-K ATPase in the lens epithelium inactivating this crucial enzyme. The consequence is that a defect in the cation pump activity arises, leading to a rapid influx of Na ions and loss of K ions and marked increase in hydration. These changes are thought to lead to opacification.


Thoracoscintigraphy in the differential diagnosis of cardiomegaly.

"Thoracoscintigraphy" is a radioisotopic scanning technique for demonstrating the nature of an enlarged cardiac shadow found on chest X-ray. The technique consists of superimposing scintiscans of the cardiac blood pool, the liver and the lungs and comparing the outline of the cardiac blood pool image with the cardiac shadow seen on X-ray. With this procedure the correct diagnosis of pericardial effusion was made in 11 of 15 patients and of pure cardiac dilatation and/or myocardial hypertrophy in three patients. In one of the patients the thoracoscintigraphic diagnosis was equivocal. Thoracoscintigraphy clearly demarcates the cardiac shadow from the surrounding organs, delineates the intracardiac blood pool within the cardiac shadow and indicates the best approach for pericardiocentesis. The procedure is harmless and noninvasive, and the radiation exposure is low and safe.


[Dermabrasion of the face].

A report is presented on dermabration of the face in 58 patients, most of which were subjected to the treatment for cosmetic reasons. The abrasion was performed under general anaesthesia with a high-speed rotary drill. The results including the complications are evaluated from the viewpoint of the physician as well as from the viewpoint of the treated patient.


Screening for metabolic disorders among high risk infants and children.

In a screening program in Cincinnati urine specimens from over 20,000 infants and children were tested for inherited metabolic disorders involving amino acids, carbohydrates, phenolic acids, organic acids, keto acids, mucopolysaccharides, and imidazoles. The subjects were selected on the basis of symptoms such as vomiting, diarrhea, acidosis, seizures, failure to thrive, delayed development, mental retardation, and others. The tests were based primarily on paper chromatographic techniques. Patients with 21 different metabolic disorders were found. The patterns of abnormal excretion of amino acids and other metabolites are often useful in making a diagnosis.


Composition and synthesis of cellular lipids in Neurospora crassa during cellular differentiation.

The synthesis of cellular lipids of Neurospora crassa was measured during growth on low (2% sucrose)- and high (15% glucose)-carbohydrate supplementation. The amount of lipid per dry weight of cells does not change during the germination and early logarithmic growth periods, but the percentage of phospholipid in the lipid does increase, reaching a maximal value of 90% at 4 to 5 h after inoculation, at which time the phospholipid content of the cells is approximately 60 mumol/g (dry weight). The content of the anionic phospholipids, as a percentage of the lipid fraction, is relatively constant during the growth period, but the contents of the zwitterionic phospholipids phosphatidylcholine and phosphatidylethanolamine change in a reciprocal fashion. During the first 8 h of growth, phosphatidylcholine falls from 53% of the phospholipid to 43%, whereas phosphatidylethanolamine rises from 29 to 38%. The total of these two phospholipids is approximately 83% during the growth period studied. The synthesis of cellular phospholipids, measured either by [32P]H3PO4 or [14C]glucose incorporation, reached maximal levels between 3 and 5 h of growth. The effect of the high-carbohydrate supplement on cellular lipids was minimal. Inclusion of 15% glucose decreased the labeling of phospholipid by [32P]H3PO4, but did not affect lipid composition. This observation is in contrast to the effects of high glucose on mitochondrial phospholipid synthesis.


Formation of sugar phosphates in colicin K-treated Escherichia coli.

Colicin K greatly decreased the incorporation of 32P-labeled inorganic orthophosphate into nucleotides and nucleic acids, causing a concomitant increase in  the formation of 32P-labeled sugar phosphates in sensitive cells of Escherichia coli. These sugar phosphates were formed in aerobically growing cells, as well as in cells under stringent control of ribonucleic acid synthesis. The main 32P-labeled product was identified as sedoheptulose 7-phosphate in two strains (B1 and K-12 MK-1) and fructose 1,6-diphosphate in one strain (K-12 CP78). The formation of sugar phosphates induced by colicin K was inhibited by carbonyl cyanide m-chlorophenylhydrazone. It was also not observed in N,N'-dicyclohexylcarbodiimide-treated cells or Mg2+-(Ca2+)-adenosine triphosphatase-less mutant (strain K-12 AN120) cells. Thus, the formation of sugar phosphates in colicin K-treated cells is dependent on the formation of adenosine 5'-triphosphate by oxidative phosphorylation.


Messenger ribonucleoprotein complexes isolated by oligodeoxythymidylate-cellulose chromatography from Neurospora crassa polysomes.

Messenger ribonucleoprotein (mRNP) complexes were isolated from ethylenediaminetetraacetic acid-dissociated polysomes of Neurospora crassa. Approximately 15% of the [3H]uridine incorporated into polysomal ribonucleic acid (RNA) during a 15-min pulse was eluted from oligodeoxythymidylate-cellulose as an mRNP complex. The isolated mRNP complexes exhibited sedimentation coefficients ranging from 15S to greater than 60S. RNA isolated from these mRNP complexes sedimented in sucrose gradients between 4S and 40S, with broad peaks at 15S and 24S. The buoyant density of mRNP complexes eluted with 25% formamide was 1.42 to 1.44 g/cm3, whereas for mRNP complexes eluted with 50% formamide it was 1.48 to 1.50 g/cm3. Six polypeptides, with molecular weights of 14,000, 19,000, 24,000, 31,000, 44,000, and 66,000, were associated with mRNP complexes eluted with 25% formamide. The mRNP complexes eluted with 50% formamide had one associated polypeptide, of molecular weight 27,000.


Coordinate regulation by iron of the synthesis of phenolate compounds and three outer membrane proteins in Escherichia coli.

The biosynthesis of the low-molecular-weight iron carrier enterochelin and of three outer membrane polypeptides appears to be coordinately regulated by the amount of cell-associated iron in Escherichia coli K-12. Measurements of iron acquisition made throughout the growth cycle in iron-deficient media indicate that a very rapid accumulation of iron occurs in the first 2 h of growth; there is comparatively little iron uptake during exponential growth, which results in a gradual decrease in the cellular iron content with each generation. When this level falls below 400 ng of iron per mg (dry weight) of cells, there is a simultaneous onset of synthesis of the three outer membrane polypeptides and of enterochelin. This coordinate regulation was also observed in cells able to transport iron actively using only citrate as an iron-carrier.


Bacillus megaterium mutant deficient in membrane-bound adenosine triphosphatase activity.

An adenosine triphosphatase (ATPase) mutant of Bacillus megaterium was isolated and characterized. This mutant (designated A37) was unable to grow on nonfermentable carbon sources and possessed less than 5% of the wild-type ATPase activity. Oxygen uptake by the mutant was comparable to that in the wild type. Sporulation in the wild type occurred in both glucose- and nitrogen-limiting media; however, A37 sporulated only in the nitrogen-limiting medium. The inability of A37 to sporulate in glucose-limiting medium seemed to be due to insufficient adenosine 5'-triphosphate (ATP) levels during the sporulation stages. Fructose, which can generate ATP via substrate-level phosphorylation, is equally efficient in stimulating ATP synthesis in the wild type and A37. Malate-stimulated ATP synthesis in the wild type was shown to have many characteristics associated with oxidative phosphorylation and was absent in the mutant. These data suggest that the ATPase deficiency results in the loss of oxidative phosphorylation.


A model compartmental syndrome in man with particular reference to the quantification of nerve function.

A human model system was used to investigate the effect of increased tissue pressure on different parameters of the function of the nerves and muscles in the anterior compartment of the leg. Abnormalities of sensation, strength, motor nerve-conduction velocity, and compound muscle-action-potential amplitude occurred in a parallel fashion when the intracompartmental pressure exceeded a threshold value. This threshold was significantly lowered by elevation of the extremity. Grossly abnormal functional parameters were consistently elicited when the peripheral pulse remained intact. The motor nerve-conduction velocity and compound muscle-action-potential amplitude appear to be reliable, non-invasive, and quantitative parameters of the physiological status of the neuromuscular tissue within the compartment.


Results of surgical treatment of idiopathic developmental stenosis of the lumbar vertebral canal. A review of twenty-seven years' experience.

Between 1948 and 1975 147 patients were treated surgically for developmental stenosis of the lumbar vertebral canal, measurement of the mid-sagittal diameters in the whole area of stenosis being performed in 116 patients. Ninety-two of these patients were followed up for periods varying between one and twenty years. About two-thirds were completely relieved fo symptoms and signs. Sciatica and intermittent claudication were more frequently cured than radicular deficit and lumbago, the latter being the most frequent persisting symptom. A permanent neural deficit as a result of the surgical procedure was noted in two cases. A detailed presentation of the technique, complications and results is given.


Increased ouabain-sensitive 86Rubidium uptake after mitogenic stimulation of quiescent chicken embryo fibroblasts with purified multiplication-stimulating activity.

Multiplication-stimulating activity (MSA), a protein which stimulates DNA synthesis and growth of chicken embryo fibroblasts, was purified from serum-free medium conditioned by the growth of a rat liver cell line. Purified MSA was shown to rapidly stimulate ouabain-sensitive Na+, K+-ATPase activity as measured by both enzyme assay and rate of 86Rubidium uptake. Labeled ouabain binding was also shown to increase after stimulation of quiescent cells by serum or purified MSA. Conditions which interfere with the ability of the cells to accumulate potassium, such as the presence of the specific inhibitor, ouabain; incubation in potassium-free medium; or the presence of the potassium ionophore, valinomycin, were all demonstrated to inhibit the stimulation of DNA synthesis by serum or purified MSA. These results suggest that an early event in the stimulation of DNA synthesis by purified MSA is an activation of membrane Na+, K+-ATPase with a resulting accumulation of potassium ions inside the cell.


The effect of myosin antibody on the division of starfish blastomeres.

Antiserum against starfish egg myosin was produced in rabbits. Antibody specificity to myosin was demonstrated by Ouchterlony's immunodiffusion test and by immunoelectrophoresis in the presence of sodium dodecylsulfate (SDS). The latter technique showed that the antibody binds to both heavy and light chains of egg myosin. Furthermore, the antibody reacted with starfish sperm mysosin and starfish adult muscle myosin at both the heavy and light chains. It did not react with bovine platelet mysosin or rabbit skeletal muscle myosin in Ouchterlony's test; however, a weak reaction was observed in the presence of SDS between the antibody and these myosin heavy chains. Ca- and Mg-ATPase activities of egg myosin were not affected by the antibody, but it did inhibit actin-activated ATPase activity of egg myosin. Microinjection of the antibody into blastomeres of starfish eggs at the two-cell stage was carried out. Anti-egg myosin gamma-globulin inhibited the subsequent cleavages at an amount of more than 0.3 ng when injected at interphase. The inhibition was reduced when the injection was carried out near the initiation of cleavage. At the onset of the second cleavage the antibody was not inhibitory; however, an appropriate amount inhibited the third cleavage. Although the disappearance of the nuclear membrane was observed in the presence of the antibody, the formation of the mitotic apparatus was more or less disturbed. However the formation of daughter nuclei seemed to be scarcely affected by the antibody except that the distance between the nuclei was significantly smaller than normal.


Assembly of the sarcoplasmic reticulum. Localization by immunofluorescence of sarcoplasmic reticulum proteins in differentiating rat skeletal muscle cell cultures.

Immunofluorescent staining techniques were used to study the distribution of the Ca(2) + Mg(2+)-dependent ATPase and calsequestrin in primary cultures of differentiating rat skeletal muscle cells, grown for different periods of time under various culture conditions. In mononucleated myoblasts calsequestrin was detected after 45 h in culture whereas the ATPase was not detected until 60 h. After cell fusion began, both proteins could be identified in all multinucleated cells. Myoblasts grown for longer than 60 h in low Ca(2+) medium contained calsequestrin and the ATPase, even though they were unable to fuse. These studies at the cellular level confirm biochemical findings on the biosynthesis of calsequestrin and the ATPase. Immunofluorescent staining of myoblasts showed that calsequestrin first appears in a well-defined region of the cell near one end of the nucleus. At later times, the staining occupied progressively larger regions adjacent to the nucleus and took on a fibrous appearance. This suggests that calsequestrin first accumulates in the Golgi region and then gradually spreads throughout the cell. In contrast, the ATPase appeared to be concentrated in many small patches or foci throughout the cytoplasm and was never confined to one particular region, although some parts of the cell often stained more intensely than others. In multinucleated cells, alternating dark and fluorescent strands parallel to the longitudinal axis of the cells were evident.


The effect of 7beta, 17alpha-dimethyltestosterone (calusteron) on testosterone metabolism in women with advanced breast cancer.

Calusterone (7beta, 17alpha-dimethyltestosterone) is a 17-alkylated, orally active androgenic steroid used in the treatment of breast cancer. The effect of this steroid on the metabolism of 14C-testosterone and the excretion of endogenous urinary androgen metabolites has been studied in four patients with breast cancer. Total glucuronide metabolites of the tracer decreased significantly, the andorsterone/etiocholanolone ratio rose by a factor of 2-4, and there was increased formation of uncharacterized polar metabolites. There was no significant change in either the sum of the excretion of endogenous androgen metabolites or the androsterone/etiocholanolone ratio. The changes resemble those we have seen in cirrhosis of the liver. It is concluded that the effects of Calusterone on testosterone metabolism, like its effects on cortisol or estradiol metabolism, represent nonspecific effects of an orally administered 17-alkylated steroid on hepatic structure and function, and probably bear no relationship to its therapeutic effect in breast cancer.


Effect of prolactin on plasma DHEA (s) levels.

Plasma DHEA and DHEA-S levels were significantly higher (P less than 0.001) in women with elevated prolactin levels, due either to chronic treatment with psychotropic drugs or to a prolactinoma, than in untreated controls. This increase was also observed in 3 male patients with prolactinoma. It is suggested that this increase is the consequence of a direct effect of prolactin on the adrenal cortex and that prolactin might be responsible for the ACTH independent andrenocortical androgen secretion.


The metabolism and 24-hour plasma concentrations of androsterone in man.

A radioimmunoassya for free androsterone permitting facile analysis of plasma taken at 20 min intervals over 24 h has revealed a curve of varying concentrations which formed a pattern similar to curves of cortisol and dehydroisoandrosterone, boht bein primary adrenal secretory products and the latter being the major precursor of androsterone. The mean of the average 24 h concentrationof androsterone in men was 55 +/- 14 ng/dl (n = 8). Such temporally related behavior requires rapid production and removal of both 17-ketosteroids, processes which have been confirmed by tracer studies where it has been shown that in a two compartment system, androsterone has a t1/2 of 25 +/- 9 min for the fast component and metabolic clearance rate of 4050 +/- 1315 L per day (n = 10). The data are in accord with an approximate production rate of androsterone which is consistent with values reported for its urinary excretion.


The intestinal brush border membrane in diabetes. Studies of sucrase-isomaltase metabolism in rats with streptozotocin diabetes.

Diabetes stimulates the functional activity of the intestinal brush border membrane with enhancement of both hydrolytic enzyme activity and membrane transport systems. To determine the mechanism of this effect, we studied the effects of streptozotocin diabetes on the metabolism of one membrane protein, sucrase-isomaltase, which increases its activity in diabetes. The protein was purified and an antiserum prepared. Sucrase-isomaltase from control and diabetic rats was immunologically identical as shown by Ouchterlony double-diffusion analysis of papain-solubilized mucosal proteins. The increase in sucrase enzyme activity in diabetic animals (31.0+/-1.4 U SEM 5 days after streptozotocin vs. 13.1+/-1.0 in controls) was the consequence of increased enzyme protein and not an alteration in catalytic efficiency as demonstrated by quantitative immunoprecipitin reactions. To account for increased sucrase-isomaltase protein in diabetes we studied papain-solubilized mucosal proteins labeled by injection of [(14)C]carbonate and [(14)C]leucine and analyzed incorporation into sucrase-isomaltase protein (anti-serum precipitable) and total protein (trichloroacetic acid precipitable). We found that diabetes did not affect the decay of labeled total protein, but prolonged the decay of labeled sucrase-isomaltase. t((1/2)) of sucrase-isomaltase was 4.4 h in control animals after [(14)C]carbonate injection and 8.8 and 10.2 h, respectively, 2 and 5 days after induction of streptozotocin diabetes. We obtained similar results in experiments with [(14)C]leucine with diabetes increasing t((1/2)) from 6 to 13.6 h. Diabetes did not appear to increase the rate of addition of sucrase-isomaltase to the brush border membrane, since it did not affect the 10- and 60-min incorporations of isotope into sucrase-isomaltase protein relative to incorporation into total protein and did not alter rate constants for synthesis calculated from the t((1/2)) and the change in enzyme mass over time.Thus, enhanced sucrase activity in the diabetic animal is the consequence of an increase in sucrase-isomaltase protein which develops because of a decrease in its rate of degradation.


Relationship between bile flow and Na+, K+-adenosinetriphosphatase in liver plasma membranes enriched in bile canaliculi.

The relationship between bile flow and Na+,K+-ATPase activity in liver plasma membranes enriched in bile canaliculi was studied in rats treated with ethinyl estradiol, phenobarbital, or 20-methyl cholanthrene. In comparison with controls (1.49+/-0.12 microliter/min per g liver), bile flow was significantly diminished by ethinyl estradiol, increased by phenobarbital, and unchanged by 20-methyl cholanthrene or the solvent, propanediol (0.92+/-0.31, 2.50+/-0.21, 1.62+/-0.18, and 1.64+/-0.30 microliter/min per g liver, respectively). The corresponding values for canalicular Na+,K+-ATPase activity were 80.7+/-19.2, 50.0+/-18.4, 231.7+/-42.6, 82.7+/-30.7, and 143.6+/-55.3 micronmol Pi/h per g liver. Canalicular Na+,K+-ATPase activity was significantly correlated (r=0.785, n=31) with bile flow. These findings support the hypothesis that a fraction of bile flow is related to Na+,K+-ATPase activity and canalicular Na+ transport.


Antibiotics for elimination of mycoplasmas and ureaplasma from bovine semen.

Minocin at 500 micrograms/ml of semen extender eliminated ureaplasma from naturally or artificially infected bovine semen. Minocin with lincospectin eliminated Acholeplasma laidlawii, Mycoplasma bovigenitalium, bovis, canadense, and arginini from artificially infected semen. Stabilization times of 15 min at 35 C and 3 h at 4 C are important considerations to maximize antibiotic activity.


An automated cerebral blood flow analyzer: concise communication.

We present an automated cerebral blood-flow (CBF) analyzer can be used as an intermittent CBF monitor during carotid endarterectomies. Given a 1-min sample of an intracarotid injection of xenon-133, this device will display a CBF value with a range from zero to 200 ml/100 g per min. Results from this CBF analyzer were compared with those from manual computations in 181 separate determinations during 51 surgical procedures. The analyzer is effective, accurate, and reliable.


Immunopatholgenesis of hypersensitivity pneumonitis.

This review describes antigenic and host factors of possible significance in the immunopathogenesis of hypersensitivity pneumonitis (HP). Although certain immunologic studies suggest immune complex mechanisms in HP, recent experimental and clinical data accumulated support a role for cell-mediated immunity. In addition, some data support roles for anaphylactic and cytotoxic antibody-mediated reactivity as well. One type of reactivity alone may not be sufficient for production of HP, and local pulmonary immune responses may be most relevant to the pathogensis. Whether immune damage will be produced in an exposed individual or not may depend on the characteristics of the antigenic exposure as well as inherited and acquired individual differences in immunologic reactivity and possibly target organ sensitivity.


Reconstruction of the acne-scarred face.

The acne-scarred face presents a challenge to the reconstructive surgeon. Dermaplaning technic with the Castro-viejo Electrokeratome ("C-V Planner") results in precise leveling of the skin. Numerous deep pit scars are amenable to small excisions; extensive milk-cheek scarring is treatable by segmental excision and reconstruction. Both dermaplaning and scalpel surgery may be required to achieve a cosmetically satisfactory result in a face badly scarred by severe acne.


Comparison of aerosolized atropine sulfate and SCH 1000 on exercise-induced bronchospasm in children.

The new anticholinergic compound Sch 1000 (ipratropium bromide) has been reported to be an effective bronchodilator without significant atropine-like side effects. We evaluated the effectiveness of different doses of nebulized Sch 1000 (40 microgram and 80 microgram) aerosolized atropine sulfate (1 mg) and placebo in the prevention of exercise-induced bronchospasm (EIB) in 20 children with atopic bronchial asthma. A random, crossover double-blind protocol was used. Standard exercise on a cycloergometer was used to induce EIB. Pulmonary function was determined before and after drug administration and exercise. Following no treatment or placebo, exercise resulted in average reductions of 33% to 43% in plethysmographic specific airway conductance (SGaw), of 20% to 25% in forced expiratory volume in 1 sec (FEV1), and of 25% to 32% in maximal midexpiratory flow rate. Exercise following no treatment or placebo resulted in average increases of 23% to 30% in thoracic gas volume (Vtg). Prior to exercise atropine and either dose of Sch 1000 caused significant increases in SGaw (48% to 59%). After pretreatment with Sch 1000 or atropine, exercise caused SGaw to fall to values that were not significantly different from pretreatment medication values, but were significantly higher than values following exercise without pretreatment or after pretreatment with placebo. No significant differences were noted between the effects of atropine and Sch 1000 on EIB. We conclude that at the doses used atropine and Sch 1000 cause equivalent degrees of bronchodilation but neither drug specifically inhibits EIB.


Functional and morphologic characterization of human T cells continuously grown in vitro.

Long-term growth (now over 13 months) of thymus-derived lymphocytes from numerous normal human bone marrow and peripheral blood cell samples was accomplished by using a factor present in media obtained from mitogen-stimulated human peripheral blood lymphocytes. This long-term growth could neither be initiated nor maintained by mitogens alone. All cell cultures were greater than 90% E rosette-positive, whereas the tests for B cell markers, surface IgG and IgM, and EAC rosette were routinely negative. There was no evidence for the presence of granulocytes, monocytes, and their precursors in these cultures. The E rosette-positive cells were then tested to see if they had T cell functions. PHA, Con A, and pokeweed mitogens stimulated lymphproliferative responses in these cultures comparable to those of fresh peripheral blood cells. These proliferating cells were also able to release cell mediators, such as interferon and colony-stimulating activity. Further evidence for the T lymphocyte nature of these cultured cells was obtained from one-way mixed leukocyte cultures in which these cells responded to but were unable to stimulate allogeneic cells. The functional and morphologic characteristics of these cultured cells show that these cells are T cells that grow continuously in vitro.


Suppression of lymphoproliferation by high concentrations of normal human mononuclear leukocytes.

Mononuclear leukocytes (MNL) include cells that suppress lymphoproliferation in unstimulated and antigen-stimulated cultures. Suppression is demonstrated by increasing the concentration of cells added to cultures and does not require preactivation of suppressor cells. Suprression of 3H-thymidine incorporation occurred if the high concentrations of MNL were added to cultures before the proliferative responses commenced. This suppressive effect of high cell concentration upon 3H-thymidine incorporation is removed by depleting MNL present in high numbers of cells that adhere to foreign surfaces or by preincubating these cells with cycloheximide, puromycin, or pactamycin. The suppressor cell, which only functions when present in a viable state, is radioresistant, adheres to foreign surfaces, remains active through 5 days in culture, and equates with the presence of a cell that is rich in cytoplasmic esterase. The suppressor cell may be of the monocyte series and did not appear to belong to either the T or the B lymphocyte series. This study provides additional evidence that normal immune reactivity in man is under regulatory control. The suppressor mechanism identified herein with normal human MNL is probably related to a similar type of suppression (but at a much lower cell concentration) that has been described with Hodgkin's disease and solid tumors.


Human lymphocytes subpopulations: rabbit red blood cell rosettes.

When human lymphocytes were incubated with rabbit red blood cells (RRBC) in vitro at 4 degrees C overnight, they adhered to form rosettes. 44 +/- 4.5% of thymocytes and o.7 +/- o.3% of peripheral blood lymphocytes (PBL) formed these rosettes. The rosette-forming cells (RFC) increased to 10--40% when the PBL were stimulated by mitogens. The increases were detected 4 h after culture and reached a maximum at 24 h, thus preceding significant increases in DNA syntheses. In another set of experiments, PBL were stimulated by a range of concentrations of each of 5 mitogens. The concentrations whick led to high DNA synthesis rates also generated high percentages of the rosettes. Lastly, PBL were activated by mitogens and the effect of inhibitors of DNA synthesis, protein synthesis and ATPase activity investigated. Only the latter could inhibit the generation of the RFC. In conclusion, 1y RRBC rosettes in mitogen stimulated human PBL were markers of activated lymphocytes, 2) the percentages of RFC could constitute a reliable index of mitogenic responses, and 3) this index was independent of the usual criteria of protein and DNA synthesis.


Coupled complementation of immune response genes controlling responsiveness to the H-2.2 alloantigen.

The ability of various B10 congenic resistant strains to respond to the alloantigen H-2.2 was tested. High and low antibody-producing strains were distinguished by their anti-H-2.2 hemagglutinating respones. However, these strains do not differ in their ability to respond to these antigenic differences in the mixed lymphocyte culture. The humoral response to the H-2.2 alloantigen was shown to be controlled by two interacting genes localized within the H-2 complex. Thus, F1 hybrids prepared between parental low responder strains could yield high level immune responses. In addition, strains bearing recombinant H-2 haplotypes were used to map the two distinct genes controlling the immune response. The alleles at each locus were shown to be highly polymorphic as evidenced by the asymmetric complementation patterns observed. The restricted interactions of specific alleles was termed coupled complementation. The significance of the results in the terms of mechanisms of Ir gene control are discussed.


Restriction-deficient mutants of Staphylococcus aureus.

A series of restriction-deficient mutants was isolated from non-lysogenic strains of Staphylococcus aureus belonging to phage groups I and II. Some mutants were sensitive to all phages tested. With one possible exception, all the mutants were unaffected in their modification systems. The breakdown of DNA of phages, restricted in the parental strains, was reduced in both the mutants that were tested. The restriction in propagating strain 3A could be transduced to its restriction-deficient mutant. The transduction efficiency increased after ultraviolet irradiation of the transducing phage suggesting that the gene for restriction is present on the bacterial chromosome.


Differentiation of fibres in human masseter, temporal and biceps brachii muscles. A histochemical study.

Masseter, temporal and biceps brachii muscles were histochemically evaluated for fibre type differentiation on 19 aborted fetuses (gestational ages 15-23 weeks), in 2 premature infants of 34 and 36 weeks gestation and in 2 fullterm stillborn infants. There was no convincing evidence of fibre type differentiation in the masticatory muscles before 22 weeks' gestation while a fairly distinct differentiation was seen in biceps brachii specimens at 16 weeks' gestation with ATPase at pH 4.35. Around 22 weeks two types of fibre were found in all specimens with ATPase at pH 4.35. With regular ATPase (pH 9.4) there was a relatively weak difference in staining between different types of fibre in the masticatory muscles. In biceps brachii Type I and Type II were demonstrated. Neonatally 3 levels of staining were seen in biceps brachii with regular ATPase (pH 9.4); while ATPase pH 4.35 and 4.6 demonstrated the subtypes IIB and IIC. In the masticatory mucles only 2 levels were recognized with regular ATPase and all type II fibres had the characteristics of Type IIC as seen with with ATPase at pH 4.35.


Nervous outflow from skeletal muscle following chemical noxious stimulation.

1. In order to determine the nervous outflow from skeletal muscle during chemically induced muscle pain, the impulse activity of various types of muscle afferents in response to close intra-arterial injections of pain-producing substances (bradykinin, 5-hydroxytryptamine, histamine and potassium) was studied in anaesthetized cats using a single fibre recording technique.2. By administration of algesic agents in doses which produce pain in man and pain reactions in animals, about half of the group IV and two thirds of the group III muscle afferents could be activated. In contrast, group II and group I afferent units were usually not excited by chemical noxious stimulation. If effects at all occurred in the thick myelinated afferents, they consisted of a depression of the fibre activity rather than of an activation.3. The qualitative features of the discharges of group III muscle afferents induced by chemical stimulation resembled those of the group IV units very closely. The group III units differed from the group IV afferents in that their responses to a given dose of bradykinin were of greater magnitude.4. It is concluded that the chemically induced muscle pain is probably mediated by certain portions of the group IV and group III afferents, whereas the reactions of group II and group I units to algesic agents are such that a contribution to muscular chemo-nociception seems improbable.


Static and dynamic fusimotor action on the response of Ia fibres to low frequency sinusoidal stretching of widely ranging amplitude.

1. Single fusimotor fibres were stimulated repetitively to test their action on the responsiveness of muscle spindle primary endings in the cat soleus to sinusoidal stretching of both large and small amplitude. Frequencies of 0.06-4 Hz were used at amplitudes from 10 mum to 3 mm.2. The response was assessed by fitting a sinusoid to the cycle histogram of the afferent firing throughout the course of the cycle; this linear approximation measures the fundamental of the response and ignores any harmonics. The sine was allowed to project to negative values and any empty bins in the histogram were ignored when fitting.3. With small amplitudes of stretching the histograms were reasonably sinusoidal, but with large amplitudes they showed appreciable distortion of the wave form for the passive ending and during dynamic fusimotor stimulation. Non-linearity of response manifested itself also, with increasing amplitude of stretching, by an increase in the phase advance of the response, by increasing r.m.s. deviation of the histogram points from the fitted sine and (for dynamic stimulation) by an increase in the mean value of the fitted sine.4. With increasing amplitude the response modulation ceased to increase proportionately with the stimulus, so that the sensitivity of the ending to a large stretch (defined as afferent modulation/stretch amplitude) was appreciably less than for a small stretch. This effect was most pronounced for the passive ending.5. Whatever the amplitude of movement the modulation during static stimulation was less than that for the passive or during dynamic stimulation. For small amplitudes the response during dynamic stimulation was less than that of the passive, but for large amplitudes the response during dynamic stimulation was always the greater. At some intermediate cross-over amplitude the two responses were the same size, though still differing slightly in other respects. The value of the cross-over amplitude was usually about 200 mum at 1 Hz, and increased on lowering the frequency. Thus dynamic fusimotor action does not uniformly produce either an increase or a decrease in the sensitivity of the ending in relation to the passive.6. Bode plots, for each amplitude, of sensitivity and phase against frequency suggested that(a) under all conditions the ending is relatively insensitive to frequency in the range studied, for the slope of the log-log sensitivity lines was only 0.15-0.2 (3.5-6 db/decade);(b) the mechanism which makes for non-linearity is not particularly frequency sensitive;(c) static fusimotor stimulation does not change the frequency sensitivity of the ending;(d) dynamic fusimotor stimulation very slightly increases the frequency sensitivity of the ending for large amplitudes.In reaching these conclusions more attention was paid to the slope of the sensitivity lines than to the values of phase.7. It appears that the major effect of fusimotor action, whether static or dynamic, is to regulate the sensitivity of the primary ending to stretching for all amplitudes of movement (i.e. gain) rather than to control the relative values of its sensitivity to length and to velocity (i.e. crudely, the damping in a feed-back loop).