Effect of chronic ethanol administration on energy metabolism and phospholipase A2 activity in rat liver. 1. For a period of 31 days male rats were given a liquid diet containing 36% of its energy as ethanol. Liver mitochondria from these animals demonstrated lowered respiratory control with succinate as substrate, a diminished energy-linked anilinonaphthalene-sulphonic acid fluorescence response, and lowered endogenous ATP concentrations. The phospholipid/protein ratio in mitochondria from these animals was unchanged; only minor alterations in the phospholipid fatty acid composition were observed. 2. In experiments where mitochondria were incubated at 18 degrees C in iso-osmotic sucrose (aging experiments), the above energy-linked properties were lost at an earlier time in organelles from ethanol-fed animals. Phospholipase A2 acitivty was depressed in mitochondria from control animals until respiratory control was lost and ATP was depleted. In contrast, no lag in the expression of phospholipase activity was observed in mitochondria from ethanol-fed rats. This loss of control of the phospholipase resulted in an earlier degradation of membrane phospholipids under the conditions of the aging experiments. 3. The ATPase (adenosine triphosphatase) activities, measured in freshly prepared tightly coupled mitochondria and in organelles uncoupled with carbonyl cyanide p-trifluoromethoxyphenylhydrazone, were not significantly different in ethanol-fed and liquid-diet control animals. When the mitochondria were aged at 18 degrees C, the activity increased with time of incubation in organelles from both groups of animals. A lag was observed, however, as the ATPase activity increased in control preparations. This lag was not present as APTase activity increased in mitochondria from ethanol-fed animals. 4. The significantly lowered values observed for energy-linked functions with succinate as an energy source demonstrate that ethanol elicits an alteration in liver mitochondria that affects the site II-site III regions of the oxidative-phosphorylation system. The apparent lack of control of the phospholipase A2 and ATPase activities in mitochondria from ethanol-fed animals suggests that the membrane microenvironment of these enzymes has been altered such that they can exert their catabolic effects more readily under conditions of mild perturbation. The fatty acid analyses demonstrate that the observed alterations both in the energy-linked functions and in control of the phospholipase and ATPase are not mediated through changes in the acyl chain composition of bulk-phase phospholipids.


Substrate cycles: their metabolic, energetic and thermic consequences in man. The role of substrate cycles in metabolic control was first indicated over ten years ago, but the recent interest in such cycles has developed from the direct demonstration by isotopic techniques of their existence in various tissues. I propose that substrate cycles form part of a logical series of biochemical mechanisms that exist to increase the sensitivity of non-equilibrium reactions to changes in concentrations of metabolic regulators. The possible importance of such cycles for provision of precise metabolic regulation in the tissues of the normal subject and the trained athlete is proposed. Furthermore, cycling may provide a mechanism by which hormones can change the magnitude of response in a tissue to a given metabolic signal, without interfering in the biochemistry of the basic control mechanism. It is, however, possible to extend the role of cycling to heat generation and thus to controlled energy loss by an organism. Heat generation by substrate cycles may be important as an acute mechanism for maintaining the body temperature in man in response to a sudden decrease in the environmental temperature; alcoholic hypothermia would be explained by inhibition of substrate cycling in the liver, and accidental hypothermia in the elderly could be explained by decreased capacity of substrate cycles with age. If heat generated by the cycles is rapidly lost to the environment, the expenditure of energy to maintain this heat loss could explain, in part, the physiological phenomena of the thermic response to food and the oxygen debt which is always observed after exercise. Finally, the energy expended in these ways could be part of a general biochemical mechanism for maintenance of the correct body weight; a decrease in the capacity of substrate cycles might be one factor involved in the development of obesity.


[Studies on the biotransformation of fominoben-HCl in man (author's transl)]. The biotransformation of 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)methyl]aminomethyl)benzanilide hydrochloride (fominoben-HCl, PB 89 Cl, Noleptan) was investigated in man. The most substantial metabolites were quantified. The metabolite patterns of fominoben in urine and plasma are compared. Fominoben, is rapidly and extensively metabolized to many metabolites. At the time of the maximum plasma level. 2 h after an oral dose of 160 mg of 14C-PB 89 Cl, only 1.5% of the plasma radioactivity can be measured as the unchanged initial compound. No parent compound can be found in the urine, only in the stool some traces of fominoben can be detected. The biotransformation can be characterized by four main pathways: 1. cleavage reactions, 2. hydroxylations, 3. cyclisations, 4. conjugations. The reactions 1--3 proceed as well simultaneously as successively.


[The effect of fominoben and oxyethyltheophylline in combination on pulmonary function and pulmonary hemodynamics in chronic-obstructive diseases of the airways (author's transl)]. Mechanics of breathing, gas exchange and pulmonary hemodynamics were investigated in 10 patients with chronic-obstructive lung diseases before and after treatment with oral doses of 160 mg 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)methyl]-aminomethyl)benzanilide hydrochloride (fominoben, Noleptan) and 300 mg oxyethyltheophylline given three times daily. The data of lung function showed a slight decrease of airway obstruction during the treatment. Hyperinflation of the lung, restriction, gas exchange were not significantly changed on the average. The main effect was an improvement of pulmonary hemodynamics: the pathologically increased mean pressures in the pulmonary artery were normalized after treatment.


Studies on the sympathomimetic effects of guanoxan on smooth muscles of rat. In anococcygeus muscle and vas deferens preparations of rat, guanidinomethyl-2-benzo-(1,4)-dioxane (guanoxan) potentiated responses to norepinephrine (NF) in concentrations which exerted a neurone blocking effect. The potentiation was significantly reduced in reserpinized preparations and was abolished in the presence of nialamide. The possible mechanisms of potentiation have been discussed. Higher concentrations of guanoxan produced concentration-related contractions. The contractions were significantly less in reserpinized preparations. Phentolamine both prevented and reversed the contractions while methysergide was ineffective in this respect. Thus the effect of guanoxan appears to be mediated through the activation of alpha-receptors by the released NE.


Performance of a shell-type heat exchanger in extracorporeal circulation. Tests were performed on a "shell" type heat exchanger used in a simulated extracorporeal circulation. The counter flow mode was the most efficient pattern and recommendations are made on which flow pattern should be employed with low water flow rates.


The effect of vitamin A acid on experimentally induced comedones: an electron microscope study. Various concentrations of vitamin A acid were applied to experimentally induced comedones. All concentrations produced non-cohesive hyperkeratinization, which loosened the cohesive horny mass induced by oleic acid and expelled it from the follicle within 7 days. The highest concentration (0.1%) produced the greatest degree of non-cohesive desquamation in the shortest time. In follicles treated with the acid, the cell membrane of horny cells was thin and ruptured easily to produce a non-cohesive debris. Desmosomes were scarce and desmosomal bodies (fusiform electron-dense bodies) and tight junctions between horny cells were not seen in follicles treated with the acid. The acid also produced hyperplasia of the epithelial wall and an apparently increased mitotic rate. A 0.025% concentration of the acid increased the number of membrane coating granules by about 70% in all regions of the follicle.


Mandibular reconstruction and craniofacial fairing. A method of restoring bony contour defects in the craniofacial regions employing a combination graft of autogenous bone and an alloplastic mesh is presented. Osteoinduction occurs within the confines of the alloplastic mesh from the cancellous bone and the resultant new bone conforms to the outline imposed by the alloplastic device. The advantages of this method include those of alloplastic materials combined with those of bone grafting. There is immediate restoration of an aesthetic contour with adequate strength and sound fixation.


Physical properties of myosin from aortic smooth muscle. Porcine aortic myosin is a smooth muscle contractile protein similar to its striated muscle counterpart. Electrophoresis in sodium dodecyl sulfate indicates that the molecule consists of three classes of subunits with polypeptide chain molecular weights of 192,000, 19,000, and 15,000. At 277 nm the absorption spectrum gives an extinction coefficient for aortic myosin of 0.558 cm2/mg; the circular dichroism spectrum of the protein indicates that aortic myosin contains about 70% of its residues in the alpha-helical configuration. Amino acid analysis shows that the smooth muscle myosin has significantly more arginine and leucine and significantly less valine and isoleucine than rabbit skeletal muscle myosin. Other studies yielded these data: Vapp = 0.716 mL/g [eta] = 0.213 mL/mg, S20, w = 5.84 x 10(-13)S. Similar studies with rabbit skeletal muscle myosin indicate that Vapp = 0.711 mL/g and S20, w = 6.36 x 10(-13)S. These properties suggest that aortic myosin, like skeletal muscle myosin, behaves hydrodynamically like a rigid rod.


Neutral protease inhibitors from human intervertebral disc and femoral head articular cartilage. Assays of several proteases, incorporating guanidinium chloride extracts of human femoral head cartilage and intervertebral disc, demonstrated that both tissues contain inhibitors of certain serine proteases. Trypsin, chymotrypsin and a granule extract of human polymorphonuclear leukocytes containing elastase and cathepsin G activities, were inhibited by low molecular weight fractions prepared by Sephadex G-75 chromatography. Using a radioassay, it was further shown that these fractions inhibit proteolysis of cartilage proteoglycan. The inhibitor in intervertebral disc is concentrated in the nucleus pulposus, with a decreasing gradient to the periphery of the annulus fibrosus. It is proposed that these inhibitors confer at least partial protection against pathological proteolysis of the proteoglycans in human articular cartilage and nucleus pulposus.


[Investigation of sarcoplasmic reticulum SH-groups]. The amount and the reaction capacity of the thiol groups in the sarcoplasmic reticulum containing up to 86% of Ca-ATPase were determined using 7-chloro-4-nitrobenzo-2-hydroxo-1,3-diazole (NBD-chloride). The total amount of SH-groups interacting with NBD-chloride is about 9 moles/10(5) g of protein as determined in the excess of NBD-chloride (750 micrometers). With respect to their sensitivity to NBD-chloride the SH-groups may be divided into two classes: slow and fast ones (5,3 and 3,5 moles/10(5) g of protein, respectively). The modification constants for the fast and slow SH-groups are 0,16 and 0,015min-1. ATP (30 micrometers) decreases the number of fast groups by 1 mole/10(5) g of protein. At higher concentrations of ATP (1--3 mM) the amount of fast SH-groups is decreased by 3 moles/10(5) g of protein, their modification rate constant being decreased 2-fold. ATP at concentration of 1 mM, decreases the rate constant for the Ca-ATPase inactivation by NBD-chloride from 0.68 down to 0,073 min-1, which coincides with the modification rate constant for fast SH-groups (0,071 min-1) under the same conditions. Ca2+ at concentration of 10(-4) M increases the amount of fast thiol groups by 1 mole/10(5) g of protein, the rate constant of their modification by NBD-chloride being increased 2-fold. A half-maximal effect was observed in the presence of 5.10(-7) M Ca2+ . Mg2+ did not affect the total amount of fast thiol groups; however, it decreased their modification rate constant.


[Effect of nitrate and cytokinin on nitrate reductase activity in isolated corncockle embryos]. The effects of cytokinin and nitrate on the activity of nitrate reductase (NR) in isolated embryos of Agrostemma githago L. were studied. It was shown that the effects of cytokinin and NO-3 on the induction of NR is additive during 8, 12 and 18 hrs of embryos incubation in the solutions of the two inducers. Anticytokinin decreased the cytokinin induced NR by 35--39% and had no effect on the NR induction by nitrate. The substrate and hormonal induction of NR differed in the duration of the lag period. This difference dependent on the physiological state of the embryos at the beginning of incubation. The data obtained are indicative of the independence of cytokinin and NO-3 effects on the NR synthesis in isolated embryos of Agrostemma githago L. Abscisic acid supressed cytokinin- and nitrate-induced NR and had practically no effect on total incorporation of the label into the protein. It is assumed that the induced synthesis of the protein is more sensitive to the action of abscisic acid that the total protein synthesis.


[Regeneration of electrical activity in anterior abdominal wall muscles following prolonged atrophy]. A possibility of restoration of the functional condition of the anterior abdominal wall muscles was demonstrated by the electrical activity parameters following long-term atrophy caused by a giant ventral hernia. Restoration of electromyographic indices was more complete when the anterior abdominal wall was stabilized with synthetic prosthesis material, since the muscle fibers in this case failed to be involved in the suture and were in functionally advantageous position.


[Complex biochemical and structural study of skeletal muscles in scoliosis]. Structural study of human scoliosis muscles showed significant dystrophic and degenerative changes: desintegration of fibrillar structure and striation; the Zencker necrosis; the replacement of muscular tissue by connective and adipose tissues. The electron microscopic observation revealed disordering of filamental array of the sarcomere (I- and A-discs), the broadening of Z-disc material, the appearance of N-stripes in I-band. At the same time deviations from the norm were observed in contractile proteins: actin and myosin. ATPase activity of myosin decreased by 25--30%; the flow of birefringence of myosin and especially of actin also decreased. Actin from the scoliosis muscles partially or completely lost the ability for polymerization in 0.1 M KC1.


[Analysis of the effect of phenamine, L-DOPA and parachlorophenylalanine on the zoo-social behavior of isolated mice]. Abnormal changes in the structure of the individual and zoo-social behaviour of isolated mice due to phenamine (amphethamine), L-DOPA or PCPA were shown. Several elements of the "pathological syndrome of isolation" in mice were found to increase under the action of the drugs studied. The extension or reduction of contacts between animals of the same species was used as an integrative indicator of recovering (resocializing) or aggravating (desocializing) effect of psychotropic drugs on the pathology of animal behaviour.


[Nature of the suppressor cells blocking the activation of DNA synthesis in mixed cultures of normal lymphocytes]. The nature of suppressor cells which are contained in lymphocyte suspension of mice immunized with allogeneic tumor cells and inhibit the DNA synthesis activation in mixed normal lymphocyte cultures has been studied. The suppressor cells are shown to be resistant to mitomycin C, X-irradiation and are not inactivated by the treatment of anti-O-serum or anti-Ig-serum in the presence of the complement. They adhere to the plastic and are inactivated by carrageenan in vitro. The macrophage nature of the suppressor cells is suggested.


[Changes in the level of epidermal G2-chalone and mitotic activity in the rat vaginal epithelium]. The content of tissue-specific inhibitor of mitosis in epidermal epithelium (G2-chalone) was estimated by a single radial immunodiffusion test in the rat vagina during various stages of the estrous cycle. The level of chalone was found to correlate with the mitotic index (MI) of vaginal epithelium. The lowest level of G2-chalone is detected in proestrus and the highest one in estrus. The level of G2-chalone in vaginal epithelium was shown to be significantly decreased in aging rats (14--16 month-old) with regular cycles as compared to that in young normal cycle rats (3--4 month-old). The single injection of estradiol benzoate (1 microgram/100 g) into ovariectomized rats led to an increase in the MI following 18 hours. The increased MI is preceeded by a substantial drop of the G2-chalone level 12 hours after estrogen injection.


Effect of mithramycin on bone beta-glucuronidase and resorption. Mithramycin suppresses bone resorption. Its effect on the synthesis and release of beta-glucuronidase (a referent for lysosomal enzymes) in mouse calvarial explants was studied in an in vitro culture system. A newly described medium (designated as KT medium) was introduced in this specific study. Mithramycin initially inhibited the release of beta-glucuronidase into the medium and resulted in an ultimate accumulation of this enzyme in the bone. These results suggest that inhibition of bone resorption by mithramycin may be attributed to interference in release of lysosomal enzymes from bone cells.


Thermal injury to the bowel as a complication of laparoscopic sterilization. Thermal injury to the small bowel occurred four times in a series of 7466 consecutive laparoscopies and tubal cauterization performed for sterilization. The four patients presented with signs and symptoms of delayed bowel perforation 4 to 11 days after the procedure. The perforations were small and involved the antimesenteric border of the terminal ileum. Histologic study of the excised specimen in one case showed full thickness coagulative necrosis of the bowel wall. Potential causes for bowel burn associated with tubal cauterization are discussed. Steps to minimize the occurrence of this complication include proper use of the laparoscope and cautery equipment, good anesthesia and gas distension of the abdomen, correct positioning of the patient and clear visualization of the operative field.


Legal opinion on position paper: withholding treatment. We have reviewed carefully the position paper and wish to provide the Association with our opinion with respect to the legal implications involved. This is one paper which clearly supports the "right to life" of newly born retarded or mentally defective infants. In our opinion, this position is entirely within the law. However, the paper does raise a number of significant legal questions which we believe warrant consideration. It is our respectful opinion that a physician, when faced with a situation of parental choice to withhold treatment, should seek the guidance of the Court and only withhold treatment or administer treatment with the back-up of a Court order.


Left ventricular hypertrophy and its reversibility in young spontaneously hypertensive rats. The development of an increased ventricular wall mass was followed from birth until five weeks of age and also later in life in spontaneously hypertensive rats (SHR) which were compared with normotensive control rats (NCR). It was shown that the first signs of enhanced ventricular growth were already evident in SHR in the first week of life. At 10 months of age left ventricular weight was 68% higher in SHR than in matched NCR, at a mean pressure difference of 30%. Treatment of SHR with antihypertensive agents, like hydralazine, hydralazine-guanethidine, propranolol, or metoprolol, from three weeks up to 10 months of age reduced this gross increase in left ventricular weight by only about 10% while the mean pressure difference between SHR and NCR was reduced by 50 to 70%. It appears that the increase in left ventricular wall mass in SHR is initiated so early in life and is of such a character that it can only, to a fairly minor extent, be reversed or prevented by pressure-lowering procedures. Part of the explanation may be a substantial contribution of myocardial hyperplasia, in association with a genetically linked predisposal to structural cardiovascular adaptation, either 'inherent' in the effectors and/or caused by 'trophic' influences of a hormonal and/or transmitter nature.


[Mediastinoscopy in haematosarcomas (author's transl)]. Mediastinoscopy allows mediastinal examination through a cervical pathway. 17 mediastinoscopies were performed on 15 children with lymphomas (5 Hodgkin disease, 10 non Hodgkin malignant lymphomas). The diagnosis was assessed by mediastinoscopy on 10 patients which had only an abnormal mediastinal opacity and were free from extrathoracic localisation. This endoscopy was done on 5 children associated with a staging laparotomy to establish a prognosis and to investigate the spread of the disease before or during treatment. Diagnosis was obtained in 14 of the 15 patients. No surgical complications was observed. However, emergency care was necessary after two anaesthesical accidents in 2 children with malignant lymphomas. Mediastinoscopy is unfrequently required in children. Although in non surgical disease such as lymphomas, it may avoid an unnecessary thoracotomy and be repeated without damage.


Glycolysis measurements in red cells from drug-treated epileptic and anaemia patients. Glycolytic activity was measured in red cells from epileptic patients treated with anticonvulsant drugs. These results are compared with measurements of red cell glycolytic activity from megaloblastic anaemia patients and normal controls. The differences obtained between epileptic patients and controls, as well as the differences between anaemia, epileptic patients and controls is discussed.


Evaluation of a topical steroid antibiotic combination (halcinonide-neomycin-amphotericin) in the treatment of cutaneous candidiasis and inflammatory dermatoses. Halcinonide-neomycin-amphotericin (HNA) cream was evaluated in the treatment of cutaneous candidiasis and inflammatory dermatoses. The anti-candidal properties of HNA were assessed in a parallel comparison with iodochlorhydroxyquin-hydrocortisone (I-HC) as the control drug. The overall therapeutic response with HNA was excellent in 38 (95%) of 40 patients as compared to 17 (43%) of 40 treated with I-HC. In 50 patients treated for psoriasis, eczematous dermatitis, or neurodermatitis, HNA was evaluated in a paired comparison with hydrocortisone (HC). The overall therapeutic response with HNA was excellent in 36 (72%) patients as compared to 18 (36%) with HC. There were no adverse reactions with HNA or the control drugs.


Early identification of handicapped children: a time for social work involvement. Early identification of handicapping conditions in children greatly enhances the possibility of treatment that may limit malfunctioning. Social work has responsibility and an opportunity to become more active in early identification.


Analysis and modelling of human motor control systems. In this contribution the aims and possibilities of model studies and simulations are briefly discussed. Next, a simulation kit for the peripheral motor control system is presented in outline and, finally, some results which can be obtained with it are given.


A physiological approach to motor disorders. Spasticity in man is presented as a disinhibition of spinal cord mechanisms, the responses to stretch depending on the interaction of the reflex effects of group Ia with those of group II afferent fibres. The reflex responses to muscle stretch and shortening in Parkinson's disease do not depend on an abnormality of spinal reflex mechanisms. The superimposition of physiological tremor or alternating tremor in rigidity produces the classical cog-wheel sensation. The phase lead of the action tonic stretch reflex was found to be reduced in patients with athetosis and cerebellar disease, thus diminishing damping of unwanted movements. The more complex transmission characteristics of the action tonic stretch reflex of normal man are absent in patients with spasticity and cerebellar lesions, presumably due to interference with long-loop pathways. In normal subjects gain of the reflex loop increases with voluntary contraction but in spasticity gain remains high irrespective of contraction level.


Phosphofructokinase isozymes from human organs and blood cells. Phosphofructokinase (PFK) isozymes of blood cells and some human tissues were studied by starch gel electrophoresis and immunoprecipitation by anti-muscle and anti-erythrocyte PFK sera. PFK from muscle, heart, brain and placenta were totally precipitated by both antisera. PFK from blood cells (erythrocytes, lymphocytes, granulocytes, platelets) were precipitated more strongly by anti-erythrocyte PFK serum than by anti-muscle PFK serum. Liver, kidney and monoblast PFK were slightly precipitated by both antisera. From the electrophoretic patterns and the immunoprecipitation curves we may conclude that muscle contains the homotetrameric M4 forms; platelet, liver and kidney the homotetrameric E4 form, and blood cells the M-E hybrids. Monoblasts probably contain a E4 type PFK precursor, and heart, placenta and brain, a modified M4 type PFK. Other isozymes, unrelated with muscle and erythrocyte, were revealed in liver and kidney.


ATP synthesis and hydrolysis in chloroplast membranes. Differential inhibition by antibodies to chloroplast coupling factor 1. 1. Divalent antibodies against chloroplast coupling factor 1 inhibited the factor ATPase, ATP synthesis, hydrolysis and Pi-ATP exchange in chloroplasts. These antibodies also inhibited coupled electron flow rates but not the basal or uncoupled rates. 2. Several types of non-precipitating, modified antibodies prepared from the original antibody preparation strongly inhibited the ATPase and Pi-ATP exchange reaction but had little effect on ATP formation. 3. It is suggested that the inhibition of ATP synthesis by the divalent antibodies is probably due to an indirect blocking of the active site, while the inhibition of ATP-utilizing reactions by the modified antibodies is related to their effect on the transfer of ATP from a non-catalytic to a catalytic site on coupling factor 1, via an energy-dependent conformational change.


Cooperation between subclass of T lymphocytes in the in vitro generation of cytotoxicity against a mutant H-2K difference. An analysis with anti-Lyt antisera. The cellular requirements for the generation of cytotoxicity in mixed lymphocyte reaction (MLR) across an H-2K mutant difference were analyzed. Treatment of C57BL/6 lymphocytes with either anti-Lyt-1 or anti-Lyt-2 serum and complement strongly reduced their capacity to mount a cytotoxic response against the B6.C-H-2ba mutant. Almost complete reconstitution of the cytotoxic response occurred when a mixture of anti-Lyt-1 and anti-Lyt-2-treated cells was allowed to respond. Once cytotoxicity was generated, only anti-Lyt-2 serum affected it. It is concluded that in the cytotoxic response to the ba mutant, Lyt-1 helper cells collaborate with Lyt-2,3 killer cell precursors in the generation of Lyt-2,3 killer cells. Lyt-1,2,3 cells play, if any, a minor role in the generation of cytotoxicity. By comparison, the capacity to generate killer cells in MLR against an H-2K + IA difference was only affected by anti-Lyt-2 and not by anti-Lyt-1 serum, indicating that this response is relatively independent of help by Lyt-1 cells under the conditions tested.


Interferon production in the murine mixed lymphocyte culture. I. Interferon production caused by differences in the H-2 K and H-2 D region but not by differences in the I region or the M locus. Little has been made previously of the observation that interferon is generated in the murine mixed lymphocyte reaction (MLR). We have found high levels of interferon in the supernatants of MLR between spleen cells of mice of different H-2 type after one to two days of culture. Interferon production was also seen in strain combinations that differed only in the K or D region of the H-2 complex. There was no production of interferon in strain combinations differing in the M locus or in the I region of the H-2 complex. The latter combinations are known not to induce cytotoxic effector cells. Thus, there seems to be a dichotomy in allogeneic determinants between those of the I region and of the M locus inducing primarily lymphoproliferation, and those of H-2K and H-2D inducing cytotoxic activity and interferon production.


MLR blast cells generated in mutant-standard strain combinations bind H-2K and H-2D antigens. Strains CBA (M523) (= M523) and CBA differ by a mutation which has been mapped genetically into the K region of the H-2 complex. Similarly, strains B 10.D2 (M504 (= M504) and b 10.D2 differ in a mutation which occurred in the D region. The data presented in this study show that mixed lymphocyte culture in M523 anti-CBA and M504 anti-B 10.D2 strain combinations leads to the release of membrane fragments from the stimulating cells and binding of these fragments by blast cells. The fragments always carry H-2K (in the M523 anti-CBA combination) or H-2D (in the M504 anti-B 10.D2 combination) antigens present in the stimulating and absent in the responding cells (antigens H-2.60 and H-2.40, respectively). Although Ia antigens may occasionally be present on the CBA membrane fragments, these antigens do not participate in the M523 anti-CBA MLR stimulation. The data thus demonstrate that serologically detectable H-2K and H-2D antigens can induce a MLR and that a mutation can change properties of H-2K or H-2D molecules so that the alteration is detectable by both serological means and lymphocyte activation assays.


Genetic and evolutionary aspects of aging. Four questions of fundamental importance to gerontology are considered. 1) The number of genes involved in aging--in the case of man, an analysis of the phenotypes of relevant spontaneous mutants indicates that aging is highly polygenic. 2) General categories of genes--regulator genes may be more relevant than structural genes: a) three aneuploid disorders, Down's, Turner's and Klinefelter's syndromes, ranked among the top 10 candidates as "segmental progeroid syndromes" when compared with 162 single gene disorders of relevance to the pathobiology of aging; b) the rates at which maximum life spans have been increasing, especially among hominids, have probably been too rapid to be accounted for by changes in the amino acid sequences of proteins; c) a preliminary analysis of the variance of maximum life spans among a few orders of mammals is suggestive of a linear correlation with the indexes of rates of chromosomal evolution, as estimated by Bush et al. (Proc. Natl. Acad. Sci. USA 74: 3942-3946, 1977). 3) Nature of gene action--although there are reasons for invoking genes that modulate the rates of accumulation of somatic mutations, differential regulation of development is likely to be a major setting for gene action. 4) New approaches to formal genetic analysis of aging--advances in experimental embryology and somatic cell genetics offer such opportunities.


[Angiolymphoid hyperplasia with follicular mucinosis]. Association of angiolymphoid hyperplasia (pseudopyogenic granuloma type) and follicular mucinosis in the same lesion on the scalp of a 30-year-old woman. A similar case has been reported recently.


Determinants of the rate of intestinal absorption of oral cholecystographic contrast agents in the dog jejunum. Successful opacification of the gallbladder during oral cholecystography depends on adequate absorption of the contrast agent from the intestine. The present studies were undertaken to define the specific characteristics of the intestinal mucosa and the properties of the various contrast agents which determine their rates of intestinal absorption. The polarity of the compounds was established by determining the ratios of their distribution between bulk solvents (benzene and water). In addition, the maximum aqueous solubility of each compound was determined. Using in vivo cannulated segments of dog jejunum, apparent passive permeability coefficients were measured. From these data, the apparent maximal rate of intestinal absorption was calculated. The six cholecystopaques studied differed markedly in polarity as judged by their varying ratios of distribution between benzene and water. The permeability coefficients varied inversely with the polarity of the compounds. However, the incremental changes in the coefficients were considerably less than the corresponding changes observed in the partition ratios. The rates of absorption of the more polar contrast agents (tyropanoate, iopronic acid, and iocetamic acid) were greater than the less polar compounds (iopanoic acid, sodium ipodate, and calcium ipodate) under the conditions in which the resistance of the unstirred water layer is not rate limiting and where bile acid micelles are not present.


Evidence against the presence of circulating immune complexes in chronic inflammatory bowel disease. Several investigators have reported the presence of circulating immune complexes in serum from patients with Crohn's disease and chronic ulcerative colitis. Because previous assays employed conditions which might have caused immunoglobulin aggregates to form in vitro, thus falsely suggesting the presence of immune complexes in vivo, we tested inflammatory bowel disease sera for immune complexes using four assays designed to minimize in vitro immunoglobulin aggregation. In three assays immune complexes were not detectable, while in a fourth, the Clq precipitin test, positive reactions occurred. These precipitin reactions did not have characteristics of immune complexes. Our data suggest that circulating immune complexes are either not present in patients with inflammatory bowel disease or that they occur infrequently or in low concentration.


[Secondary extra-uterine pregnancy (author's transl)]. The article reports on a patient with secondary extra-uterine pregnancy during the 20th pregnancy week. The highly multifaceted symptoms and the diagnostic possibilities are discussed on the basis of this case. Laparoscopy is rated decisively important.


["Second-look laparoscopy" (author's transl)]. The authors present a report on their experience with the so-called "second-look laparoscopy" which they have been performing systematically since 1974. 44 (12%) second-look laparoscopies were done among a total of 383 laparoscopies during 1974--1977. Second-look laparoscopy was performed on routine basis in women treated by radiology and/or pharmacotherapy for advanced carcinoma of the genitals, especially in the case of ovarian carcinoma. The diagnostic measure represents an important contribution to establishing whether chemotherapy has been successfull, especially in ovarian cancer.


Treatment of Paget's disease of bone.

Treatment of Paget's disease of bone. A brief review is given of the use of fluoride, mithramycin, glucagon, actinomycin D, calcitonins and diphosphonates for treatment of Paget's disease of bone. The decision regarding treatment, effectiveness of the drugs, the incidence of side effects and assessment of clinical, biochemical, histological, radiological and thermographic responses are discussed.


Enzyme histochemical alterations in human skeletal muscles after tenotomy and after spontaneous rupture of the tendon. The authors studied the histochemical alterations of human skeletal muscles after tenotomy and after spontaneous rupture of the tendon. Both succinate dehydrogenase (in type I fibers), and myofibrillar ATP-ase (in type 2 fibers) activity was decreased in all injured muscles. In the intact antagonists and contralateral muscles alterations were not found. The creatine phosphokinase and aldolase activity were decreased also in injured muscles. The lactate dehydrogenase activity was various both in affected and in unaffected muscles. Two weeks or more after the injury of the tendon in injured muscles the number of type 1 fibers were decreased and therefore a mathematically significant type 2 fibre predominance occurred. Atrophy involve both type 1 and type 2 fibers, but type 1 fibre atrophy was more pronunced as type 2 fibre atrophy.


[Effect of 1 alpha-hydroxycholecalciferol on cellular calcium metabolism of kidney cortex (author's transl)]. Rats were provided a normal laboratory diet or a low Ca.vitamin D-deficient diet. After the administration of 1 alpha-hydroxycholecalciferol, mitochondria, microsomes and slices were prepared from kidney cortex of both control and treated rats. When 1 alpha-hydroxycholecalciferol was given to normal and low Ca.vitamin D-deficient rats, Ca accumulation in mitochondria was stimulated during 30 minutes and the high calcium content was maintained at the subsequent incubation. There was a significant decrease of mitochondrial Ca2+-ATPase and Mg2+-ATPase activities with low Ca.vitamin D depletion, but both enzyme activities were restored by 1 alpha-hydroxycholecalciferol treatment of the depleted rats. Ca2+-ATPase and Mg2+-ATPase activities of microsomes were not altered with the administration of 1 alha-hydroxycholecalciferol. In contrast to results of mitochondrial Ca transport, changes in Ca influx and efflux of slices were not significant in response to the treatment of low Ca.vitamin D-deficient rats with 1 alpha-hydroxycholecalciferol. The results of the present study suggest that 1 alpha-hydroxycholecalciferol plays a role in the process of Ca accumulation and ATP hydrolysis of mitochondria in kidney cortex.


[Computer tomography of the cervical spinal canal following intrathecal enhancement: cervical CT myelography. Studies on technic and the initial results (author' transl)]. Computer tomography of the cervical spinal canal was carried out in 54 patients after the intrathecal injection of metrizamide (CT myelography). In 43 patients this was done after conventional myelography, in eleven it was the primary examination. In 32 patients the examination proved normal and in 22 abnormal. Correlation between the CT findings and conventional myelography was excellent. Quite small intraspinal structures both normal and abnormal, could be demonstrated. CT myelography is particularly valuable for determining the special relationships within the vertebral canal. The procedure can supplement and confirm conventional myelography, for instance round the foramen magnum. Under certain circumstances it may be regarded as the method of choice, since it is simpler for the patient and less likely to produce complications due to the contrast medium.


[The collateral circulation due to cerebral arterio-venous malformation and occlusions of major cranial vessels (author's transl)]. Arteriovenous malformations (AVM) of the brain are diagnosed mostly in the early adult life. With the come up of Computerized Tomography (CT) which often is done without the strong indications as postulated for the conventional neuroradiologic examinations, asymptomatic AVM in the elderly population may be found. Since May 1977 4 asymptomatic arteriovenous malformations were diagnosed in our institution using CT. 2 of these patients had severe degenerative changes of the great cerebral vessels and an unusual collateral circulation developed probably because of the steal-phenomenon in the vascular malformation. These 2 cases allow to study all possibilities of cerebral collateral circulation. Uncommon in one of the cases was a capillary anastomotic network through the thalami, in the other case an extensive dural rete mirabile developed. The problems of collateral circulation are discussed.


[High contrast doses for peripheral and cerebral angiography (author's transl)]. Angiography, using a standard method, was carried out on 100 patients with arterial occlusive disease involving the cerebral and/or peripheral vessels. It was shown that contrast medium with a high iodine content could be used in the relatively high dose of 80 ml. with an injection rate of 30 ml/sec. in the cerebral circulation without producing any complications. For pelvic and lower limb arteriography, 80 ml. contrast was injected at a rate of 12 to 18 ml/sec. This was well tolerated, but produced "vascular pain" like all commercially available contrast media. Total contrast amounts reached 300 ml. and 4.8 ml/kg. body weight and were tolerated without any clinical evidence of toxicity. Mild side effects were observed in seven patients, unrelated to the amount of contrast or the type of contrast or the region investigated. These changes resolved rapidly without treatment. As a rule the vessels demonstrated angiographically showed good contrast and were easily seen.


[Bilateral selective renal angiography--a procedure worth while? Report of the incidence of bilateral space-occupying lesions of the kidney in 2721 selective renal angiographies (author's transl)]. Since surgeons can save part of one kidney either by partial resection or reimplantation following "workbench" surgery, it has become increasingly important for the radiologist to demonstrate bilateral space-occupying lesions of the kidneys by bilateral selective angiography, magnification technique and computerized tomography of the kidneys. Fine-needle puncture of the kidney is an important additive technique to solve differential diagnostic problems of avascular, space-occupying renal lesions. Moreover it is a great comfort to the surgeon to know the appearance of both kidneys and may also modify the planned surgical procedure considerably. The incidence of 93 cases of bilateral space occupying lesions of the kidneys, diagnosed in 2721 selective renal angiographies over a period of 13 years, suggests that these entities are more frequent than previously thought.


[Malignant tumours in horseshoe kidneys (author's transl)]. Hypernephromas were found in horseshoe kidneys in two patients; the diagnostic problems arising from this combination are discussed. Detailed demonstration of horseshoe kidneys by excretion urograms may be poor and tumours may therefore be overlooked and, on palpation, an abnormality within the gastrointestinal tract may be simulated. Angiography usually indicates the diagnosis and helps in planning surgery. Although there is no increase in the incidence of adeno-carcinomas in horseshoe kidneys, there is a significant increase in the incidence of Wilm's tumours and of carcinomas of the renal pelvis. Treatment consists of heminephrectomy or resection of the tumour; complications are relatively common.


[The scope and value of translumbar puncture of the renal pelvis (author's transl)]. Percutaneous translumbar pyelography is indicated when excretory urography has failed to demonstrate the cause or site of obstructive uropathy and retrograde pyelography is impossible, undesirable or contraindicated. Under prophylactic treatment with antibiotics translumbar antegrade pyelography is safe, simple and accurate and in selected cases the only diagnostic method to establish exact diagnosis without which appropriate therapy cannot be planned. The method is described and the results of 30 percutaneous translumbar pyelographies obtained from 2680 renal angiographies and 230 punctures of space-occupying lesions over 13 years are reported.


Fibrolipomatosis of the transplanted kidney. Fibrolipomatosis of varying degree was observed in 24 transplanted kidneys. In 8 patients there was no history of urinary tract obstruction or multiple infections, leaving earlier rejection periods as the probable factor responsible for development of fibrolipomatosis after transplantation.


[Oro-pharyngeal oesophagus papillomatosis. Description of one case (author's transl)]. A case of oro-pharyngeal oesophagus papillomatosis is described. It was associated with an adeno-carcinoma of the stomach. A brief, critical review of the literature with consideration of the aetiology and pathology is given.


[Evaluation of liver haemodynamics by spleno-portography in portal hypertension (author's transl)]. In 68 patients arterial and portal blood flow were measured by angiodensitometry in the course of routine, indirect splenoportography. Results were compared with those already published, with investigations of a model and with animal experiments. It was shown that, given certain underlying conditions, reliable results can be obtained even in the presence of a pulsatile flow and incomplete contrast mixing. Compared with other procedures, the method has the advantage of providing a complete picture of liver haemodynamics in the course of routine splenoportography in a simple way and without affecting the patient further. As a result the indications for performing a shunt and the choice of the shunt technique can be more accurately determined.


[Diagnostic criteria for pancreatic sonography during the course of uncomplicated acute pancreatitis (author's transl)]. The course of uncomplicated pancreatitis was followed by sonography in 45 patients. The changes during the disease and their temporal relationship to the clinical stage are illustrated by an example. During the initial phase of the disease the sonographic findings may be so slight that they are easily missed, although clinical symptoms are present. It is only during the main phase of the disease that the typical sonographic findings of acute pancreatitis develop. At this time, maximal increase in amylase activity has usually passed. During recovery, with uninterrupted clinical and biochemical improvement, changes in the sonogram can still be seen for between three weeks and four months.


[The sonographic differential diagnosis of supra and infra diaphragmatic processes (author's transl)]. The sonographic features and differential diagnosis of 95 supra and infra diaphragmatic processes are described. Sonographic demonstration of the diaphragm permits definite differentiation between simple and loculated pleural effusions from periparenchymatous fluid collections in the abdomen.


[Lymph node metastases--diagnosis by lymphography and CT (author's transl)]. The value of lymphography and CT in the diagnosis of abdominal lymph node metastases was compared in 82 patients with various types of malignant disease. In the presence of systemic disease or testicular tumours, CT increased the recognition of lymph node metastases and their extent, particularly of high para-aortic deposits which were frequently underestimated by lymphography. Lymph nodes in the pelvis are more easily identified. CT is the first choice for the investigation of systemic disease and testicular tumours. This will, in addition, also demonstrate abnormalities of the organs and assist in radiation planning. CT is a simple procedure which is also very valuable in following the effect of treatment. For metastases from other origins, lymphography is often more valuable since CT is unable to identify metastases in lymph nodes if these are not enlarged. The two methods complement each other and their combination provides improved diagnostic information.


[Percutaneous fine needle biopsy of lymph nodes (author's transl)]. Following lymphography, 76 lymph nodes were punctured percutaneously using a fine needle in 23 patients and an aspiration biopsy was performed. This simple procedure provided cytological comfirmation in cases of doubtful lymphograms. Systematic puncture of representative lymph nodes in the area of metastatic spread may at times be able to replace a staging operation.


Angiography in synovitis of the knee.

Angiography in synovitis of the knee. In inappropriately treated synovitides of the knee joint with shift towards a villonodular inversion, an inflammatory angiographic symptomatology may be expected which is different according to the seriousness of the illness including (1) local hyperaemia, (2) deviation of arteries, (3) morphologic and formative vascular inversions and (4) diffusion of the contrast material into synovitic conglomerates and (5) shunts. From these findings the stadia of synovitis may be evaluated, including the extent and place of the villonodular inversion in the clinically or arthrographically inaccessible sites. Differential-diagnostic contributions to the origin of the synovitis cannot be expected from angiography and biochemical as well as bacteriological methods (cultivation) remain necessary. Despite this, angiography has its supplementary value in all cases where an analysis of synovitis is impossible by other means and also in all cases, where the extent of the synovitic changes must be evaluated for an operative treatment.


Roentgenmorphological muscle changes in anterior horn cell lesions. The author examined muscles in the extremities of 42 poliomyelitis patients using a special roentgenological technique. This method made it possible to objectively determine the size of the muscles in the soft tissues of the extremities. The volume and distribution of the increased amounts of fatty tissue in the muscle and the volume of normal muscle tissue led to draw conclusions regarding the histological state of the muscle. Roentgenmorphological changes are closely linked to muscle dysfunction. Roentgenological examination of the soft tissue provides a useful supplement to a muscle biopsy and to electromyographic examinations and is of value for the rehabilitation of the patients.


[Mammography in the diagnosis and treatment of non-puerperal mastitis (author's transl)]. Circumscribed or diffuse non-puerperal mastitis is usually associated with local signs of inflammation. In two-thirds of these cases it is possible to demonstrate the radiological features of mastitis. Mammography is an important diagnostic procedure in the demonstration of acute mastitis and its differentiation from an inflammatory carcinoma; it is also valuable in the control of treatment. The success of intensive antibiotic therapy with recovery of normal appearances in the chest can be observed objectively by mammography. In distinguishing mastitis from an inflammatory carcinoma, radiological evidence of regression under the influence of antibiotics is evidence in favour of mastitis.


[Experimental study on image quality when using screens in mammography (author's transl)]. 1. Different type of screens and x-ray films have been investigated using a Kodak mamma-phantom I.T.O. 745 and compared with conventional non screen industrial film radiography. 2. Dosisreduction by using screens depends on the used film/screen system. It is possible to reach a relation of 1 : 10. 3. The information depends on type of screen and of type of film. Therefore, it is possible to reach the information of non screen industrial film radiographs. 4. A suitable film/screen system allows without loss of any diagnostic information to replace non screen industrial films needing a high exposure dosis by a film/screen system needing decreases dosis.


[Dose measurements during mammography using a grid (author's transl)]. In order to increase film contrast, the Mammo Diagnost U (Philips) has been equipped with a newly developed grid. The apparatus was used with a film-screen combination in a clinical investigation (film: 3M type M,  screen: Kodak Min R, cassette: Kodak Min R). The paper deals with dose measurements on patients and phantoms who had been x-rayed by the apparatus. Measurements were carried out with a low kv. chamber and a LiF dose meter which were calibrated for various kv. ranges. The tissue equivalent phantom was a modification of the phantom substance M3; this was preferred to the usual substances such as Plexiglass or Vestyron because of its more suitable physical properties. A breast compressed to 5 cm. irradiated with 35 kv. receives an entry dose of about 1.4mC/kg. (5.3 R) corresponding to a maximal surface dose of about 31 mGy (3.1 rd.). In order to determine radiation dose to patients, measurements were carried out on an Alderson phantom using four different techniques. Surface dose to the contralateral breast and the lens was about 1% and .1% of maximal surface dose of the irradiated breast. Gonadal dose was less than 0.4 muGy (40murd.) per exposure.


[Futher means for reducing radiation dose during exposure of the pelvis in infants (author's transl)]. A simple dose-saving procedure for the diagnosis of congenital hip dysplasia employing a diaphragm in nearfocus position is presented. Doses to the skin and the gonads were measured with a phantom for the new and other techniques. With optimal techniques the skin dose is smaller than 2 mR and the gonadal doses lie around 0.1 mR for both male and female patients. An estimate of the dose burden from undesired radiation is appended.


[Correlation between radiological, scintigraphic and histological changes in bone in rabbits following irradiation with single and fractionated doses (author's transl)]. The left hind legs of eight rabbits were irradiated with 1.750 rad in a single dose or with 4,650 rad divided over a period of three weeks. These animals, as well as four who had not been irradiated, were examined periodically radiologically and with 99m Technetium pyrophosphate scintigrams during one year. No difference could be detected between the results of the single and fractionated doses. Scintigraphically there was a biphasic increase in uptake, the first peak co-inciding with the irradiation and of vascular origin, whereas the second peak occurred at four months and was due to a change in bone metabolism. At the end of a year uptake in the irradiated limb was slightly reduced. The earliest radiological changes were found after six months, at the end of the second scintigraphic peak; they consisted of coarsening and blurring of the trabeculae, nonhomogeneous spotty mineralisation and endosteal scalloping. Six animals developed a radiation-induced bone sarcoma, first demonstrated either by scintigraphy or radiology depending on its histology. The value of combining radiological and scintigraphic examinations for the early detection of post-radiation abnormalities is stressed.


Reflux of metrizamide into the lateral ventricles in vomiting. Two cases are presented in which metrizamide refluxed into the lateral ventricles after vomiting, the contrast having been brought in intrathecally by lumbar route for CT-scanning of the basal cisterns. It is suggested the intrathoracic and intraabdominal pressures transority achieved in vomiting are transmitted to the spinal canal through the vertebral venous plexus. This results in a pressure which is transmitted through the C.S.F. to the posterior fossa, and from there, for anatomical reasons, to the ventricular system. Transitory dilatation of the ventricles results in aspiration fluid from the fourth ventricle, and hence reversal of normal flow in the aqueduct of Sylvius.


[Real time demonstration of the carotid and other peripheral arteries by ultrasound (echo arteriography) (author's transl)]. A newly developed ultrasound apparatus for use in angiologic diagnosis is described. The apparatus is a real time scanner with significantly better resolution than commercially available scanners. The carotid artery in the neck and major arteries in the arms and legs can be traced well into the periphery. An extremity can be examined in about ten minutes. It is possible to estimate the diameter of the vessel, the border between wall and lumen, its branches, amplitude and rhythm of pulsation and the relationship between the artery and its neighbouring tissues. The procedure is painless, has no side effects and therefore can be repeated as often as necessary.


Coarctation of the abdominal aorta.

Coarctation of the abdominal aorta. Coarctation of the abdominal aorta is an uncommon process but an important cause of systemic hypertension. Angiography is the investigation of choice to establish a diagnosis and document the extent of involvement. However, angiography does not provide an etiological diagnosis; and it may not be possible to distinguish an acquired coarctation from a congenital process. Three patients with coarctation of the abdominal aorta are presented.


[Arterio-venous angioma of the kidney: embolisation and two year follow-up (author's transl)]. Successful embolisation of an arteriovenous angioma of the kidney with gel foam suspension is described, with a two year follow-up. Embolisation cured hypertension, which had otherwise resisted treatment, and stopped haematuria. The need for careful follow-up is stressed with long-term observations using both angiography and scintigraphy of the affected kidney. The intra-arterial embolisation with gel foam resulted in a redistribution of blood-flow which led to complete success of treatment even thought the vascular malformation had not been totally obliterated.


[The effect of contrast volume on the radiographic demonstration of the gall bladder and bile duct (author's transl)]. No differences could be detected subjectively in the quality of cholangiograms after the use of varying amounts of contrast medium (20 and 30 ml iodoxaminic acid). Pharmacolinetic data which would indicate the use of either quantity are not available. Densitometric measurements carried out by us showed no significant statistical difference between the results of using 20 or 30 ml iodoxaminic acid.


[Improvement of oral cholecystography and cholangiography with ceruletid (author's transl)]. Following oral cholecystography in 100 patients, the conventional "fatty meal" was replaced by an intramuscular injection of Ceruletid in a dose of 0.4 microgram/kg body weight. The synthetic decapetide Ceruletid is a substance with a hormone-like effect on the gastro-intestinal tract. It contracts smooth muscle in the gut and stimulates secretion in the stomach and the exocrine pancreas. Compared with other substances producing contraction which are given orally, Ceruletid acts more quickly and more powerfully in producing contraction of the gall bladder muscle. In 86% of positive cholecystograms, this resulted in satisfactory demonstration of the bile duct, 66% better than for oral substances. Many abnormalities, particularly localised adenomyomatosis, can only be diagnosed after good contraction of the gall bladder. Side effects, such as nausea, dizziness and a feeling of heat were transitory. In three patients it led to vomiting. The rapid and certain effect of Ceruletid during oral cholecystography requires reassessment of the role of intravenous cholangiography in diagnosis. Particularly amongst out-patients, with a high proportion of normal gall bladders, it is possible to complete the examination in one stage by demonstrating the bile duct with Ceruletid.


[The diagnosis and treatment of malignant haemangiopericytomas (author's transl)]. Two cases of malignant haemangiopericytomas are described; one was a multiple tumour, the other arose from the mediastinum. The difficulties of diagnosis, and particularly differentiation from lymphangiopericytoma, are stressed. Irradiation of the tumour is a useful addition to the forms of treatment.


[Radiographic examination of tracheal strictures by means of powdered tantalum (author's transl)]. This report deals with the diagnostic value of a tracheobronchography with powdered Tantalum in 5 patients who suffer from a severe stricture of the trachea. The own experiences with this method are described.


[Gynaecomastia and mammography (author's transl)]. The term gynaecomastia indicates an increase in the mass of the normally rudimentary male breast; morphologically there is hyperplasia and differentiation of the epithelial and mesenchymal breast components. Gynaecomastia is not a disease in itself, but a symptom of some underlying disease or the result of drugs. Of 2895 breast operations performed at the surgical clinic of the University of Göttingen, 2.97% were operations on men with gynaecomastia. Amongst 79222 mammograms in the Radiological Clinic of the University, there were 900 mammograms (1.14%) of 392 men with gynaecomastia. Most benign and malignant conditions in men are retromammary in localisation. For this reason clinical evaluation is frequently wrong. The use of mammography as an additional diagnostic method in men is therefore more important than it is in women. Systematic analysis of the mammograms performed on men has made possible a classification of gynaecomastia according to the radiological appearances: I Septal linear structures (8.5%), II Opacities of varying density and size (26.5%), III Circular, usually inhomogenous shadows (15.5%), IV Homogeneous, demarcated foci of varying size (35.5%), V Soft-tissue hyperplasia-pseudo-gynaecomastia (10%).


[The diagnostic significance of microcalcifications in testicular tumors (author's transl)]. The evaluation of total orchiectomy tissue specimens with malignant testicular tumors shows that microcalcifications can be found in a surprisingly high percentage by radiological and histological examinations. Small, often in several groups located calcifications in the parenchyma neighbouring the tumor are typical for seminoma, whereas in teratoma solitary microcalcifications and polymorphic types can also be seen. Microcalcifications are also present in not neoplastic testicular diseases but in a much smaller percentage and with a different type of calcification. The preoperative radiographic examination of testicular tumors of unknown origin seems to be indicated as a non-invasive method able to provide further information about the presence of a malignant germ cell tumor. Regarding the genetic risks of the method, there is hope to avoid other more invasive examinations with their danger of tumor spreading and to enable a radical resection of the primary tumor before its metastic formation by the mean of preoperative orchioradiography.


[Polysegmental andersson lesion in ankylosing spondylitis (roentgenological-histological synopsis) (author's transl)]. Basing on roentgenological observation of the course of the disease, and on postmortem examination, of a patient with polysegmental Andersson lesions (known as spondylodiscitis) in ankylosing spondylitis, the article reports on the histological and often also clinico-roentgenological possibility of differentiating between an inflammatory and non-inflammatory type of this destructive lesion. The non-inflammatory type of Andersson lesion reflects a fracture due to fatigue, or its sequel, eg pseudarthrosis, in the stiffened axial skeleton. In this particular patient, renal osteopathy had favoured the genesis of the disease.


[Comments on the problem of non-specific sclerosing spondylodiscitides (author's transl)]. After reviewing types of sclerosis of the vertebral bodies and spondylodiscitides occurring near the vertebral discs, the causes of which are relatively well known, two observations of cases of chronic progressive sclerosing spondylodiscitis are described in detail together with their case history. The primary manifestation (in the lumbar vertebral column) is seen, apart from a discitis, in a relatively early and eventually homogeneous sclerosing of the spongiosa. The course of the disease is extremely protracted; after 1-5 years, other parts of the vertebral column are affected in a similar manner. Inflammatory parameters are definitely involved, and the nosological neighbourhood to angylosing spondylitis is discussed. In the absence of any other hints, it appears justified to assume non-specific chronic progressive sclerosing spondylodiscitis which begins monostotically and can proceed according to a polystotic pattern.


[The importance of scintimetry in the differential diagnosis of roentgenological areas of increased "translucence" in the skeleton of children (author's transl)]. A random selection of lesions representing osteolytic bone processes was evaluated with the "region-of-interest" technique in order to determine whether scintimetry can be helpful in the differential diagnosis of such processes in children. Bone tumours with structural densification, as well as osteomyelitides, were reviewed for comparative purposes. It was found that scintigraphy of the skeleton, while supplying additional and clinically quite interesting information, does not make any substantial contribution to the differential diagnostic clarification of roentgenological translucence in the skeleton of children.


[A comparison of the side effects of water-soluble contrast media for lumbar myelography (author's transl)]. A prospective comparison study of the water-soluble contrast media Amipaque and Dimer-X was performed on 200 lumbar myelograms. During this investigation, and amongst a total of 1702 myelograms with Dimer-X, there were only transient mild side effects; these were somewhat more common with Amipaque. There were no sequelae, particularly those of a neurological nature. After careful clinical examination, and by observing certain precautionary measures, it is possible to perform lumbar myelography with water-soluble contrast media on an out-patient basis.


[Conventional-radiographic and computer-assisted cisternography of the posterior fossa with metrizamide (author's transl)]. Conventional radiographic and computer-assisted (CT) cisternography of the posterior fossa using Metrizamide was carried out in 25 and 33 patients respectively. The contrast medium was injected by the lumbar or cervical route. During conventional cisternography, contrast medium distribution is most easily controlled by a lateral injection at the level of the first to second cervical vertebra. Because of its physical properties, Metrizamide results in good demonstration of detail. CT cisternography is usually able to demonstrate an extra-cerebral space-occupying lesion with a diameter greater than 1 cm. This procedure has fewer complications due to the contrast medium or the technique, since small amounts of Metrizamide achieve an adequate increase in the density of the CSF; it is therefore possible to inject this by a lumbar route and to carry out the entire examination with the patient supine. Both conventional and CT cisternography permit very accurate diagnosis in the region of the foramen magnum. Both procedures can be used on their own or as an addition to conventional Metrizamide myelography.


[Image characteristics of the computer tomograph (author's transl)]. In the present paper the images produced by spheres of varying diameter (d = 4,6,8,10 mm) embedded in a homogeneous substance of varying densities (H' = 3,48,93,137 Hounsfield units) as produced by computer tomography were studied. Measurements show that for each sphere diameter there is a minimum contrast between the substance of the sphere and its surroundings which must exist in order to show this sphere by computer tomography. It was also shown that the partial volume effect is of significance for the attenuation of the spheres. The effect of the position of the spheres within the slices to be imaged was studied. The results clearly indicate that in the investigation of small tissue changes in the body, the thickness of the slice and patient displacement should be kept as small as possible.


[Computer tomographic longitudinal sections of the trunk reconstructed from standard cross-sections (author's transl)]. Reduction in scan times and advances in the field of image reconstruction have made it possible to reconstruct the trunk from sequential coronal sections. For this purpose 8 mm cuts without overlap are suitable. There is consequently no increase in patient dose or in the scan time. Longitudinal sections can be reconstructed by a dedicated computer in about 10 minutes and cross sections can be evaluated in more detail. The longitudinal reconstructions provide better demonstration of organs and space-occupying lesions in their craniocaudal extent. This extension of the diagnostic spectrum is of value to the diagnostician and particularly to radiotherapists and surgeons during treatment planning.


Is there a future for single photon emission tomography? Emission tomography has the potential to be developed into a clinically useful technique. Its clinical applications, however, will be limited and not in the main stream of space occupying disease detection but in the definition of quantitative information particularly relevant in those disease processes where the metabolic component is the most important one. Special purpose designed instrumentation may prove to be the best of several possible compromises.


[Computer tomography in acute pancreatitis (author's transl)]. The computer tomographic appearances of acute pancreatitis have been analysed 33 patients. It is usually a simple matter to distinguish between the acute, oedematous pancreatitis, which can be treated conservatively, and the suppurative pancreatitis with haemorrhagic and necrotising features, which require surgical exploration.


[Computerized tomography of the liver. Accuracy of the method in biopsy proven diagnoses (author's transl)]. To evaluate the diagnostic accuracy of computerized tomography (CT) in detecting liver disease, CT-findings of 320 patients examined with a slow CT-scanner (2.5 min scanning time/slice) could be compared to the results of bioptic procedures. Sensitivity was 81% for circumscript liver disease, specificity was 85%. In 69% of the cases, a type-specific diagnosis of circumscript liver diseases was possible, this percentage increased by 5% if patients with a true-positive differential diagnosis were included. 73% of the patients with liver metastases were correctly identified to have metastatic liver disease. Obstructive jaundice was correctly identified in 77% and correctly excluded in all patients with medical jaundice. For a large variety of hepatocellular disease, ratio of true positive diagnoses was 16% only. The value of CT in hepatocellular disease concerns exclusion of presumed space-occupying lesions. In a control group of 310 patients with only "clinically" and not bioptically confirmed diagnoses, specificity was 96% and sensitivity concerning focal liver disease was 82%. Our results prove CT to be a valuable non-invasive tool in the evaluation of circumscript liver disease.


[Computer-cardio-tomography in idiopathic hypertrophic subvalvular aortic stenosis--a new contribution to non-invasive diagnosis (author's transl)]. The use of computer tomography as a non-invasive procedure in the diagnosis of idiopathic hypertrophic subvalvular aortic stenosis is described. Seven patients were investigated in whom the diagnosis had been confirmed by echocardiography and laevocardiography with pressure measurements. Details of the method are discussed and computer tomography and echocardiography are compared. The features of greatest differential diagnostic importance relating to asymmetrical septum hypertrophy are discussed.


[Computer tomographic demonstration of the popliteal artery entrapment syndrome (author's transl)]. The popliteal artery entrapment syndrome can be diagnosed by computer tomography with a greater degree of certainty than by angiography. The advantage of computer tomography depends on the simultaneous demonstration of the position of the vessel and of the surrounding muscles and their abnormal situation.


[Radiological and scintigraphic evaluation of hip prostheses (author's transl)]. The radiological findings following the introduction of hip prostheses are often equivocal. Additional bone scintigrams often provide important information for the evaluation of the prostheses. 1. An unstable hip prosthesis is characterised by abnormal uptake in bone, due to static and mechanical stress. 2. A positive scintigram does not necessarily indicate instability of the prosthesis. Increased uptake may also be due to inflammatory bone changes, healing, bone replacement, abnormal local stresses or soft tissue calcification. 3. In evaluating the scintigram one must take account not only of the intensity of isotope uptake, but also its distribution and exact localisation. 4. It is essential to compare the scintigram with the radiograph. Radiological features of possible instability become diagnostic if they correspond to appropriate increased radioactivity. If the latter is absent, the of instability remains doubtful. 5. In some cases early loosening of the stem of the prosthesis can be diagnosed while the radiograph is still negative. Increased radioactivity in the acetabulum is frequently seen in the presence of a stable acetabular prosthesis and must be interpreted with caution as a sign of loosening of the prosthesis.


[Baker cysts: an accompaniment of chronic diseases of the knee joint (author's transl)]. One hundred and twenty one Baker cysts demonstrated by arthrography have been analysed. Morphologically one must distinguish between distension cysts and dissection cysts. Distension cysts are more common with various diseases of the knee joint (68% of all cysts). Dissection cysts (32%) are found particularly with inflammatory-rheumatic diseases and are rarely of degenerative or post-traumatic origin. Acute rupture of the cyst was observed on ten occasions. Repeated rupture, which had only been suspected previously, was demonstrated by arthrography in four patients. It is pointed out that Baker cysts may imitate the features of acute thrombophlebitis.


[Gardner's syndrome. three patients with varying manifestations (author's transl)]. Fully developed Gardner's syndrome is characterised by the triad of intestinal polyposis, osteomas and multiple soft tissue tumours. Absence of any one of these manifestations results in a bisymptomatic form. We describe three patients, one woman and two men aged 40, 46 and 51 years. In two patients the triad was fully expressed, but with varying organ involvement. The third patient was of the bisymptomatic type with osseous and intestinal lesions.


[The clinical and radiological picture of degenerative disease of the extra- and intra-cranial vessels (author's transl)]. The clinical and angiograms of 500 patients with degenerative disease of their cerebral vessels were evaluated. The clinical severity of the ischaemic changes was graded and compared with localisation and extent of the angiographic abnormality. In these patients there is an increased risk during angiography and a careful technique has to be employed. Two examples are used to show that it is possible to clarify even complex neurological and angiographic problems by means of an appropriate technique, 90% of our patients with a definite cerebral infarct gave a history of previous transitory ischaemic attacks. In our opinion patients with these attacks are of particular interest to the angiographer and the surgeon.


[Partial aplasia of the right internal carotid artery with an unusual collateral circulation below the hypophysis (author's transl)]. A case of partial aplasia of the right internal carotid artery with an unusual artery passing through the skull base below the hypophysis is described. An association between the presence of this vessel and recurring abnormalities of eye movements with alternating ptosis is assumed. The ontogeny and phylogeny of this collateral artery are discussed.


Areae gastricae and gastritis in double contrast barium meal. The areae gastricae were studied in patients with different forms of gastritis and with normal gastric mucosa. The material consisted of 57 patients. First gastroscopy was done and biopsies were taken. The stomach was studied on the following day by the double contrast barium meal. The material was divided according to the gastroscopic and biopsy findings into the following groups: normal, superficial gastritis, mixed gastritis, and atrophic gastritis. In the analysis of the surface pattern, special attention was paid to the shape, size and defects of areae gastricae. Corpus and antrum were dealt with separately. In the normal material the areae gastricae were regular in shape, and the size was usually 1--3 mm. Irregular shape, bigger size and more frequent defect areas seemed to point to gastritis. Such changes were especially clear in atrophic gastritis. The significance of the areae gastricae in practice is discussed.


[Hypernephroma in a pelvic kidney. Diagnostic problems during angiography (author's transl)]. A hypernephroma in a pelvic kidney of a 54-year-old patient is described, which could not be demonstrated angiographically. This is explained by marked compression of the kidney because of the limited available space and the pressure of the surrounding organs. There was also histological proof of advanced intimal fibrosis in the artery and extensive obstruction of the vein by tumour, leading to diminished circulation of blood. The extreme rarity of hypernephromas in pelvic kidneys is stressed; this is barely mentioned in the literature.


[Sonography, computer tomography and angiography in the diagnosis of an haemangioma of the renal pelvis (author's transl)]. A renal pelvis haemangioma is described, which was diagnosed by means of sonography and angiography. The angiographic criteria are enumerated. The sonographic findings have not previously been described. Their value in the diagnosis, and in differential diagnosis, is discussed.


[Percutaneous nephropyelostomy in children (author's transl)]. Percutaneous nephropyelostomy with a fine needle technique was performed successfully in 20 out of 21 children with urinary tract obstruction. The procedure was of value in assessing the recovery of renal function and for measuring perfusion pressure. As a therapeutic measure the method was used to preoperatively in children who were severly ill, and post-operatively for the treatment of complications after surgery on the urinary tract. A complication seen in two children was repeated dislodgement of the catheter.


Nonsurgical removal of intravascular foreign bodies. With increasing use of indwelling venous catheters, embolization of intravascular catheter fragments has become a well-known complication. Because of the high risk and serious complications, embolized fragments should be retrieved whenever possible. Four cases of successful nonsurgical percutaneous catheter retrieval (two adults and two children) are described using a wire loop and a hook-shaped catheter technique. The method described allow a safe and rapid retrieval and should always precede surgical exploration.


[Transfemoral aspiration of a thrombus from a renal artery with an angiographic catheter (author's transl)]. Thrombosis in a renal artery occurred in a 60-year-old woman after regional hypothermia of the kidney for which balloon occlusion of the artery had been used. Perfusion of the kidney was re-established by aspiration and flushing of the thrombus; this was confirmed angiographically and anatomically. Renal function did not recover, however, since removal of the thrombus by means of an angiographic catheter was carried out too late. We regard early aspiration of emboli from major abdominal vessels as a further application of arterial catheterisation by the Seldinger technique.


[Determination of the iodine content of the thyroid by means of fluorescence scans (author's transl)]. A procedure is described in which stable 127I in the thyroid is induced to fluorescence (28.5 keV) by 241Am (59.5 keV). The radiation is registered on a Si (Li) detector and can be used in order to obtain a scintigram or to determine the concentration of127I in the thyroid at any selected point. The apparatus is available commercially and has been adapted for use with a scanner. Measurements using collimation of 3.5 to 4 cm revealed a focus with a marked tomographic effect. The sensitivity of the apparatus was investigated by using solutions of varying iodine concentrations; calibration curves for determining iodine concentration in thyroid tissue were obtained. It is necessary to take account of the thickness of the thyroid gland and of the superficial tissues because of the marked attenuation of the radiation within the tissues. Radiation dose to the thyroid during the scintigram was about 0.1 mGy (10 mrd), i.e. about 5% of a conventional TC scintigram. There is no whole body irradiation.


[Reduction of radiation-induced late effects on vascular connective tissue of the skin (mouse paw) by o-(beta-hydroxyethyl)-rutoside]. The induction of irreversible late effects of the skin after irradiation of the mouse foot with and without i.p. HR-application has been investigated. The high protective effect of HR could be demonstrated which prevents grave late damage such as loss of toes. One single application of 300 mg/HR 0,5 h before irradiation has been optimally successful. Beside the excellent compatibility of even high doses, HR seems to have the advantage to be a selective radiation protection substance with a protective effect only for healthy cells (in this case presumably the vascular systems) and no effect on malignant cells. The possible mechanism of the stabilization of oxidative phosphorylation by flavonoids and a depression of glycolysis in malignant cells will be discussed.


[Regression of diabetic glomerular changes following islet transplantation. A study of rats with streptozotocin diabetes]. The precise etiology and pathogenesis of diabetic glomerulosclerosis still remain obscure. The aim of the present study was 1. to evaluate the morphologic and functional alterations of mesangial cells in long term diabetic rats and 2. to study the effect of islet transplantation on these lesions. Diabetes was induced in inbred Lewis rats with streptozotocin (65 mg per kg). 7 month later glomeruli of diabetic rats showed hyaline nodular deposits, exsudative lesions and glomerular aneurysms. The thickening of the mesangium measured by point counting method was statistically significant compared with age matched controls. Large quantities of IgG, beta 1c and fibrinogen in a predominantly mesangial pattern could be demonstrated by fluorescence microscopy. After injection of aggregated immunoglobulin the uptake of IgG by the mesangial cells was delayed in the diabetics compared with normal controls. Islet transplantation resulted in a marked reduction of the light microscopic and immunohistological glomerular lesions and restored the phagocytic capacity of the mesangial cells almost completely. From these results it is concluded, that the fundamental defect in diabetic glomerulosclerosis is a metabolically induced functional defect of the mesangial cells.


[Menarche in healthy and sick girls with special reference to mongolism]. The age of menarche in various groups of females was studied. In healthy girls, the average age of menarche was 12 years 2 months regardless of their birthweights. Twin girls had a significantly retarded menarche (approx. 12 years 8 months). In a group of 102 blind patients, it was not significantly different from healthy controls. In a series of 42 girls with mongolism, the mean age of menarche was significantly retarded (13 years 3 months).


Further studies on the relationship of adrenal and gonadal steroids in pubertal development in female rats. Surgical adrenalectomy or the administration of aminoglutethimide, corticosterone (B), and androstenedione (delta 4) to the immature female rat had no effect on the timing of vaginal membrane opening. Dehydroepiandrosterone (DHA) and estrone (E1) significantly hastened vaginal patency. Aminoglutethimide increased pituitary LH content while FSH content was decreased. An anti-17 beta-E2 antibody increased pituitary LH content and plasma concentration suggesting enhanced synthesis and release of LH. Pituitary FSH content was unaltered while plasma FSH decreased. Aminoglutethimide increased adrenal and ovarian but not pituitary weight while the antibody had no effect. Since little DHA is present in rat plasma and adrenal and since only estrogens have any effect on the onset of puberty, it is likely that the adrenal is not directly involved in pubertal development in the female rat.


Kartagener's syndrome and the syndrome of immotile cilia. Kartagener's syndrome (KS) is a hereditary disease with typical symptoms of situs inversus, bronchiectasis, and chronic infections of the nasal mucosa. Autosomal recessive inheritance cannot be doubted on account of repeated observations of affected sibs and parental cansanguinity. The bronchopulmonary symptoms in sibs, however, cannot be explained by this mode of inheritance. Recent clinical findings and electron microscope investigations suggest that KS is a special form of manifestation within the immotile cilia syndrome. This disease combines the typical bronchial and nasal symptoms of KS with sterility in the male due to immotile sperm tails and, as a facultative symptom, situs inversus. Thus, sibs with bronchiectasis but without situs inversus are also classified under this syndrome. The symptoms mentioned are caused by an abnormal morphology of bronchial cilia and sperm tails, which can be demonstrated by electron microscopy. The dynein arms normally attached to the nine microtubular doublets and providing a normal ciliary movement are lacking. It is assumed that during early embryonic life ciliary beats in the growing embryo determine the type of laterality. When ciliary movements are absent laterality may develop fortuitously, thus effecting a situs inversus in about half the affected cases. The numerical evaluation of pedigrees from the literature supports this assumption.


Origin of trisomies in human spontaneous abortions. Chromosome heteromorphisms of 34 trisomic abortuses and their parents were compared to determine the origin of the extra chromosome. Fourteen of the trisomies were maternal in origin, ten resulting from a first-meiotic-division error and four from either first- or second-meiotic-division errors. No paternally derived trisomy was identified.


Pericentric inversions of chromosome number 9: benign or harmful? Pericentric inversions of chromosome number 9 have been  studied in 4 different probands: a normal female with designation 46,XX,inv(9)(p12q13); a male with Down syndrome designated as 47,XY,+21,inv(9))p13q13); a premature infant with multiple, congenital malformations who was 46,XX,inv(9)(p12q21), and a Down syndrome proband with 47,XYqs,+21,inv(9)(p13q21). All 4 cases were shown to be inherited based on family studies. These families are discussed with reference to the literature as to what possible effect this structural change could have on the reproductive capability of a normal carrier and what  guidelines are available for counseling such a carrier.


A new N-acetyl-beta-D-hexosaminidase disease with late onset of progressive neurological symptoms. Clinical data are presented on a 30-year-old male with normal early development (4-5 years) but subsequent progressive impairment of psychomotor functions. He has marked kyphoscoliosis and talipes calcaneo-valgus. The organs appear normal and the patient can walk unaided and feed himself although he does not recognize his parents. He has normal fundi oculi. Biochemical data show an absence of mucopolysacchariduria and very low but detectable levels of N-acetyl-beta-D-hexosaminidase in serum and leucocytes. The clinical symptoms are much milder than would normally be expected from such a profound enzyme deficiency (Sandhoff disease).


The role of monocytes in phagocytosis and mixed leukocyte reactivity in human acute myeloid leukemia. Lymphocyte proliferation, as measured by incorporation of tritiated thymidine (3H-TdR), was significantly enhanced (p less than 0.01) when macrophages sensitized by target myeloblasts were added to monocyte-depleted lymphocyte fractions in the mixed leukocyte reaction (MLR) with human leukemic myeloblasts as stimulators and panels of normal lymphocytes as responders. Monocyte addition in the same concentration range to unfractionated lymphocytes resulted in highly significant facilitation (p less than 0.0001) of MLR response patterns to myeloblastic stimulation. However, with substitution of a different myeloblastic stimulator, this facilitation was not observed. At higher monocyte-lymphocyte ratios (1:15) the monocytes appeared to be capable of strongly inhibiting the MLR. Monocyte capacity to engulf and kill Candida albicans organisms was normal in acute myeloid leukemia (AML) patients given "immunotherapy" with BCG and leukemic cells.


Stimulating capacity of blast cells from patients with chronic myelocytic leukaemia, in blastic crisis in 'one-way' mixed lymphoycte reaction: lack of evidence for T lymphoblastic conversion. It has long been suggested that the blastic transformation in some patients with Ph1-positive chronic myelocytic leukaemia (CML) may be lymphoid in nature. It has recently been postulated that some patients with CML may undergo a T lymphoblastic crisis because the leukaemic blasts from these patients have high terminal deoxynucleotidyl transferase (TdT) activity and that some patients may undergo a non-T/non-B lymphoblastic crisis since leukaemic blasts from a majority of morphologically lymphoid type CML-BC cases react with antiserum specific for non-T/non-B acute lymphoblastic leukaemia (ALL). The present study shows that leukaemic blasts from each of six patients with Ph1-positive chronic myelocytic leukaemia-blastic crisis (CML-BC) exerted a strong stimulation on allogeneic lymphocytes in 'one-way' mixed lymphocyte reaction. There was no apparent difference in stimulating capacity between morphologically myeloid type (four cases) and lymphoid type (two cases). The stimulating capacity of leukaemic blasts from patients with CML-BC was quite similar to that of blasts from all patients with acute myeloblastic leukaemia (AML) and from some patients with non-T/non-B type ALL. Leukaemic blasts from a patient with T-cell type ALL and cultured leukaemic T lymphoblastoid cells (2 lines) consistently failed to stimulate while cultured leukaemic null-cells (4 lines) consistently exerted a strong stimulation in 'one-way' mixed lymphocyte reaction. These observations suggest that leukaemic cells from patients with CML-BC, morphologically lymphoblastic type, are not T lymphoblasts although the possibility that these cells are non-T/non-B lymphoblasts cannot be ruled out entirely.


Use of stimulating capacity of mixed lymphocyte reaction (MLR-S) as a possible marker for the cell-origin of null-cell acute lymphoblastic leukaemia. The recent introduction of surface marker analysis indicates that the T-cell ALL represents 15--25%, the B-cell ALL represents less than 5% and the null-cell ALL represents more than 70% of cases. The origin of leukaemic null-cells is at present not clear. The present study shows that fresh leukaemic cells from five patients with null-cell ALL exerted a strong stimulating effect while the leukaemic cells from three patients with null-cell ALL failed to stimulate in 'one-way' MLR. Cultured leukaemic cells from three null-cell lines (NALM-16, NALL-1 and MOLT-10) consistently exerted a strong stimulation while leukaemic cells from one null-cell line (REH) exerted little or no stimulation on allogeneic lymphocytes. Leukaemic null-cells from the NALM-,6 line exhibited a lesser but significant stimulation in 'one-way' MLR. These observations lead us to speculate that leukaemic null-cells which possess a stimulating capacity may represent less differentiated leukaemic B lymphoid cells (early B-cell precursors) and leukaemic null-cells which possess no stimulating capacity may represent less differentiated leukaemic T lymphoid cells (early T-cell precursor).


Rhodamine as a fluorescent probe of lymphocyte activation. Fresh rat and mouse lymphoid cells have been labelled by stable linkage with tetramethylrhodamine isothiocyanate (TMRITC). A change in intensity, either an increase or decrease of the fluorescent emission of the cells, detected by microfluorimetry, was induced by mitogen stimulation or the mixed lymphocyte reaction. The change in fluorescence was observed within 3 h of mitogen stimulation and within 0.5 h in the mixed lymphocyte test. These early cellular responses were detectable consistently whether the labelling was done before or after mitogen stimulation; post-labelling only was studied in the mixed lymphocyte reaction. The method should provide a time-saving practical procedure for early detection of the lymphoid cell responses and would readily lend itself to flow cytofluorimetry for possible routine diagnostic use.


Enhanced release of lipase from stimulated mouse spleen cells. We detected lipase activity in an homogenate of mouse spleen- and lymph node cells by using [3H]-triolein as a lipase substrate. Lipase activity was also detected in an homogenate of human peripheral blood lymphocytes. Furthermore, in mouse spleen cell culture medium we observed increased lipase activity following stimulation of mouse spleen cells with phytohaemagglutinin (PHA) as well as allogeneic spleen cells. Therefore, we suggest that lipase may be a kind of lymphokine.


Functional depletion of T- and B-memory cells and other lymphoid cell subpopulations-during trypanosomiasis. T. brucei infection in mice causes generalized immunosuppression with multiple changes in the cells of the lymphoid tissue. Loss of B cell responsiveness to antigens and mitogens, and the induction of suppressive T-cells and macrophages, have been previously reported (Hudson, Byner, Freeman & Terry, 1976; Corsini, Clayton, Askonas & Ogilvie, 1977; Jayawardena & Waksman, 1977). In this study, purified B- or T-cell populations from infected mice have been tested functionally in vitro or in vivo by transfer into syngeneic irradiated hosts to separate the cells from trypanosomes or their products. B-memory cells for thymus dependent (DNP-KLH) and thymus independent (DNP-Ficoll) antigens are depleted or lose their potential to respond to the antigen during T. brucei infection. Similarly, purified T-helper cells, and T-cells reactive to allogeneic target cells in mixed lymphocyte reactions are functionally defective. By 16 days of infection all these responses are less than 10% of the normal level. The loss of B-cell function follows the peak parasitaemia and is accompanied by increases in the serum levels of both IgM and IgG. Enhanced Ig production and decline in B-cell potential also occur in T-deprived mice and in CBA/N mice which lack a subset of T-independent B-cells. Cells affecting delayed hypersensitivity reactions retain their activity throughout trypanosome infection and so far provide the only exception to the general decline in immune potential.


Human-mouse mixed lymphocyte cultures. II. Partial separation of functionally distinct populations on discontinuous albumin gradients. Human-mouse mixed lymphocyte cultures (MLC) develop stable, strain-specific responses directed towards antigens determined by the mouse major histocompatibility complex (MHC). By restimulation in vitro a two- to four-fold increase in total cell numbers can be achieved. Sensitized cells can be fractionated on discontinuous BSA gradients to produce fractions with predominantly proliferative or cytotoxic activity towards the intiating antigens. Mixing experiments show that fractionation of biological activity is the result of fractination of specifically sensitized effector cells rather than fractionation of inhibitory or collaborative elements. Since biological activities or can be separated on the basis of physical properties into distinct cell populations these experiments support the idea that these functions are the properties of distinct subclasses of human T lymphocyte. Xenogeneic MLC coupled to physical separation measures is a useful approach to the study of antigen-specific human T lymphocytes.


The blastogenic response of rabbit lymphocytes stimulated with autologous cells. Rabbit WBC and spleen cells respond with marked blastogenesis and mitosis when cultured with mitomycin-C treated autologous sacculus rotundus, appendix and Peyer's patches cells in the one-way rabbit mixed leucocyte reaction (MLR). A lesser response is observed using stimulating cells of the other lymphoid organs. The blastogenic response in the one-way 'autologous MLR' cannot be attributed to mitogenic factors released from the mitomycin-C treated stimulator cells since it is also observed in the 'two-way autologous MLR', using untreated stimulator cells. Several explanations are proposed to account for the 'autologous MLR'.


Virus plaque assay: effective detection of virus plaque forming cells at the early stage of lymphocyte activation by mitogen and alloantigen. Activated lymphocytes were detected quantitatively by virus plaque assay (VPA) during the course of lymphocyte cultures stimulated by mitogen or alloantigen. In Con A-stimulated cultures, the number of virus-plaque forming cells (V--PFC) was a more sensitive method of detecting the early stage of lymphocyte activation than [3H]-thymidine (3H-TdR) incorporation. This evidence was obtained by two methods of collecting cells of each stage. First, when Con A-activated lymphocytes were fractionated by velocity sedimentation at unit gravity to separate cell populations according to each cell stage, the ratio of the number of V-PFC to the radioactivity of incorporated [3H]-TdR was larger in the earlier stage of cell cycle than in the later stage. Second, when cultured lymphocytes were synchronized directly by addition of excess thymidine and colchicine, similar results were obtained. In primary mixed lymphocyte cultures, the generation of cytotoxic lymphocytes (CTL) was correlated better with the proliferative response than with V-PFC production. It was also found that both the incorporation of [3H]-TdR and the generation of CTL were abrogated by cytosine arabinoside (Ara-C) added to cultures up to one day before assay, whilst the generation of V-PFC was not so markedly affected by Ara-C. These findings suggest that V-PFC represent the number of precursor cells which require one or more generations to differentiate to CTL and not simply the number of effector lymphoyctes already exhibiting cytotoxicity.