Physiologic determinants of the electrocardiographic diagnosis of left ventricular hypertrophy. The relative importance of left ventricular (LV) geometry, wall thickness, and mass on the inscription of left ventricular hypertrophy (LVH) on the ECG was examined in 93 patients; 36 had no LVH on the ECG, 10 had borderline voltage for LVH, and 47 had LVH on the ECG. LV cineangiograms in the right anterior oblique projection were analyzed for LV end-diastolic volume, free wall thickness (h), semiminor radius (R), LV mass index (LVMI), and the geometric relations described by h/R, mass/volume, and h . R. Although mean LVMI was greater in patients whose ECG voltage was either borderline or diagnostic of LVH, increased LVMI also occurred without LVH on the ECG. None of the variables (h, R, h/R or mass/volume) reliably indicated when LVH would be inscribed on the ECG. The product of h . R, however, defined three electrocardiographic groups; all patients with LVH on their ECG had h . R greater than 2.6 cm2. Wall thickening sufficient to result in an increased LV mass did not result in LVH on the ECG unless sufficient concurrent chamber dilatation was present. Thus, a critical geometric relationship resulting from the interplay of wall thickness and chamber dilatation is necessary for LVH to appear on the ECG. This finding is consistent with the solid-angle theory of electrocardiography as it relates to ventricular hypertrophy.


Results of ophthalmosonometry and supraorbital photoplethysmography in evaluating carotid arterial stenoses. A total of 263 patients underwent either periorbital ophthalmosonometry (Doppler ultrasound) or a combination of ophthalmosonometry and supraorbital photoplethysmography (SOPPG) to determine the presence or absence of a hemodynamically significant lesion (occlusion or greater than 50% reduction in lumen diameter). There were 522 vessels studied with Doppler ultrasound and 272 vessels with a combination of the two modalities. The tests were correlated with carotid arteriography to determine their accuracy. Overall accuracy of the Doppler ultrasound examination was 95%. A normal Doppler ultrasound examination was obtained in 367 vessels and arteriography confirmed the absence of a hemodynamically significant lesion in 93%. Of 155 vessels with an abnormal Doppler examination, 149 (96%) were proven on arteriography to have hemodynamically significant lesions. The Doppler ultrasound examination had a high incidence of false-negative examinations (26%) in those vessels that were between 50% and 99% stenotic, however. The SOPPG alone had a high incidence of false-positive examinations (19%); however, in 155 vessels with a normal SOPPG, 98% were proved to have no hemodynamically significant lesion. The combination of Doppler ultrasound and SOPPG was highly accurate in identifying patients with hemodynamically significant lesions. Of 97 vessels with such lesions, 96 (99%) had either an abnormal Doppler ultrasound examination or an abnormal SOPPG. In 240 vessels with concordant results of the Doppler ultrasound and SOPPG, the presence or absence of a hemodynamically significant lesion was accurately predicted in 235 (98%).


Beneficial effects of pulsatile perfusion in the hypertrophied ventricle during ventricular fibrillation. To assess the potential benefit of pulsatile perfusion inthe hypertrophied heart during fibrillation, 10 dogs with left ventricular hypertrophy, produced by previous supravalvular aortic banding, were used to compare linear and pulsatile perfusion in the fibrillating heart during total cardiopulmonary bypass. The mass spectrometer was used to measure subendocardial PCO2 and PO2 (PmCO2 and PmO2), and radioactive microspheres were utilized to measure myocardial blood flow in the same layers. Pulsatile perfusion was established using the recently develop "bubble tubing," which produces a pulse pressure of at least 20 mm Hg and can be used in a standard roller-pump apparatus. Both linear and pulsatile flows were compared at mean aortic root pressures of 80 and 50 mm Hg, and these four combinations of aortic root pressure and type of flow were employed for periods of 30 minutes each. Myocardial ischemia developed during linear coronary perfusion at 50 mm Hg, as evidenced by an elevation of PmCO2. Ischemia was not evident during pulsatile perfusion at the same mean pressure. Reversal ischemia was a result of increased myocardial blood flow and pulsatile perfusion, and this increase was shown to occur maximally in the deeper subendocardial layer. Ischemia was not eviden during linear or pulsatile perfusion at an mean perfusion pressure 80 mm Hg. Thus, if lower perfusion pressures are to be tolerated in patients with left ventricular hypertrophy, pulsatile perfusion with the bubble tubing technique may prevent the development of subendocardial ischemia or infarction.


Identification of keratan sulfate in liver affected by Morquio syndrome. Glycosaminoglycan content, composition and molecular weight were determined in liver obtained from a patient with Morquio syndrome (Mucopolysaccharidosis IV). There was about a four-fold increase in glycosaminoglycan content (as hexosamine) of the affected liver as compared to the control liver. The major glycosaminoglycan accumulated in the liver was keratan sulfate, which was not found in the control liver. Chondroitin sulfates, especially chondroitin 6-sulfate, were also increased. Heparan sulfate isolated from the liver of a patient with Morquio syndrome was structurally different to that from control liver, and the glycosaminoglycans from Morquio syndrome were of a much lower molecular weight than those from control.


Racial and sexual differences in the standard electrocardiogram of black vs white adolescents. Standard 12-lead electrocardiograms were recorded in 114 healthy adolescents to substantiate possible influences of race and sex on the "juvenile pattern" (increased precordial voltages of QRS complex, precordial T wave inversions, and ST-segment elevations considered pathologic in adults) in this age group. Black male subjects had the highest precordial QRS amplitudes and the highest incidence of biphasic or negative precordial T waves and ST-segment deviations. In white male subjects, these findings were less pronounced but were more evident than in black or white female subjects. Results indicate the following: (1) race-specific and sex-specific normal electrocardiographic standards should be developed in adolescents; (2) criteria for left ventricular hypertrophy are race-specific and sex-specific and should be tested against independent anatomic or physiologic information in adolescents with left ventricular overload; and (3) the "juvenile pattern" may be viewed as a predictable continuum of age-related changes starting in childhood and progressing through adolescence on to later life.


Atrial depolarization in Wolf-Parkinson-White and Lown-Ganong-Levine syndrome: vectorcardiographic features. The atrial depolarization pattern was studied in 22 patients with Wolff-Parkinson-White and Lown-Ganong-Levine syndrome. The influence of the accessory pathways on the shape, magnitude and conduction pattern of the PSE loop was analyzed. An accurate evaluation of the beginning of the delta wave and of the P loop distortions was obtained by using high magnification (1 mV = 30 cm) recordings. The Frank lead system was used. The influence of atrial size (documented by echocardiography) on the PSE loop is emphasized. Special attention has been focused on the terminal vectors as compared to a control group. In Wolff-Parkinson-White syndrome the size of the PSE loop was smaller than in Lown-Ganong-Levine syndrome or in the normal group. When atrial conduction disturbances and/or atrial enlargement was present the PSE loop was larger and distorted. The terminal vectors were abnormally oriented in 75 percent of the patients with Wolff-Parkinson-White syndrome, but only in one with Lown-Ganong-Levine syndrome. The beginning of the delta wave in patients with Wolff-Parkinson-White syndrome was located to the left of the E point in all but two. When the "concertina" effect was present, the direction of the terminal vectors remained unchanged. In four patients with the Lown-Ganong-Levine syndrome, the PSE loop closed, and in three patients, a small opening was present. We suggest that the changes in contour, duration and amplitude of the PSE loop are due to an abnormal pattern of atrial depolorization in Wolff-Parkinson-White syndrome.


Effects of platinum antitumor agents on in vitro assays of human antitumor immunity. I. Effects of cis-[pt (NH3)2Cl2] on the mixed lymphocyte tumor assay. Human lymphoblast cell lines (LCL) were treated with the antitumor complex Cis-[pt(NH3)2Cl2] (CPDC). Direct effects of CPDC treatment on LCL growth, as well as on LCL recognition by human lymphocytes in vitro are reported. Treatment of LCL with 10 micro m CPDC strongly inhibits DNA and protein synthesis, but has little effect on LCL viability. At this concentration, CPDC also inhibits the proliferation of human peripheral blood lymphocytes (PBL) in response to mitogens or allogeneic cells. Therefore, studies of LCL recognition by human PBL were conducted using CPDC pretreated and extensively washed LCL. Recognition of CPDC pretreated LCL in the in vitro mixed lymphocyte tumor (MLT) cell assay for the activation phase of cellular immunity is reduced. The decrease in MLT response is not due to direct effects of the complex on the responding T lymphocytes, but may be due to lowered antigen expression of treated LCL or other mechanisms. If CPDC does enhance tumor rejection in vivo, it does not appear to be due to enhanced recognition by T cells.


Studies on the mode of action of 5-fluorocytosine in Aspergillus species. The mode of action of 5-fluorocytosine (5-FC) was studied in three isolates of pathogenic Aspergillus with varying degrees of susceptibility to the drug. Distribution studies showed that susceptibility or resistance to 5-FC was not dependent on uptake of the drug. While only a small percentage of the total 5-FC taken up was found in the RNA fraction of the cells, most remained in the acid-soluble intracellular pool. 5-FC, 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine monophosphate (5-Fd-UMP) were among metabolites identified in the pool. In addition, fluoroorotic acid appeared to be a major constituent of the metabolites derived from 5-FC. The aspergilli also were capable of utilizing cytosine as a nitrogen source and this is suggested as a possible mechanism of resistance. A dual mode of action for 5-FC in the aspergilli is proposed. This consists of, first, incorporation of 5-FU into RNA and, second, inhibition of DNA synthesis by production of 5-FdUMP.


[Changes in allogeneic immune response of swine in the course of a liver allograft]. Pig liver allografts showed a typical rejection crisis. The degree of rejection depended on the SLA-typing. Despite SLA-incompatibility pig liver allografts can be tolerated. Short-term survivors showed an immunological hyporeactivity. Long-term survivors reconstituted their cellular immune-reactions and developed an antibody which appeared to function as an antigen-antibody-complex or an anti-Ia-antibody.


[Evidence of a specific defect in effector cell formation following kidney and liver allotransplants in humans]. In 5 recipients of cadaver kidney allografts and 1 patient with an orthotopic liver transplant specific in vitro reactivity of blood lymphocytes against donor antigens was monitored by means of the unilateral MLC assay and an indirect cytotoxicity assay (using MLC activated recipient lymphocytes as effector cells in a 51Cr release assay). The liver patient and 3 of the kidney graft recipients developed a specific defect in the capability to generate cytotoxic effector cells in vitro. Proliferative reactivity against donor lymphocytes was retained in these patients.


[Regression of left ventricular hypertophy in the ECG during antihypertensive treatment: preliminary observations (author's transl)]. Typical signs of left ventricular hypertrophy (LVH) were present in the ECG of 36 (10 women, 26 men) of 127 persons with essential hypertension (46 women, 81 men). After a two-year course of combined drug treatment (chlortalidone, reserpine, methyl-dopa, hydralazine) with effective blood-pressure reduction LVH was still present in the ECG of 29, after a four-year course of only 15 among 36, i. e. a reduction in the presence of LVH of nearly 60%. Since the patients' body-weight remained unchanged during this period, the regression in ECG changes is ascribed to the effectiveness of the drug treatment.


Statistical survey of gynecological laparoscopy/pelviscopy in Germany till 1977. By mailing, 1.365 questionnaires to gynecologists, 265,900 laparoscopies/pelviscopies were reported in 682 questionnaires (49.2%) by anonymous answer. These had been performed by 380 gynecologists (hospitals) between 1949 and 1977 in Germany. 302 gynecologists who answered the questionnaires (44.2%) are not using the endoscopic technique. Till the end of 1977 in Germany monopolar high-frequency current was used in 52%, bipolar high-frequency current was used in 42%, and modern endocoagulation was used in 25% for the purposes of hemostasis. 240 hospitals (63%) are mainly using pelviscopes of 5--8 mm diameter, 124 hospitals (33%) are using laparoscopes of 11 mm diameter. All together 949 (3.56%) complications had occurred which necessitated 690 laparotomies (2.59%). Cause of these complications were damages to vessels and burns by high-frequency current. 24 (0,09%) deaths were reported which had occurred during or following the intervention, that is one death for 11,000 pelviscopies. Mortality due to this method can be itemized as follows: 13 deaths (0.09%) in 140,977 (53%) diagnostical laparoscopies/pelviscopies, 3 deaths (0.08%) in 37,639 (14.2%) diagnostical-operative pelviscopies, 8 deaths (0.09%) in 87,284 (32.8%) sterilizations. Since 1974, however, the mortality rate is smaller than 1 : 100,000. Since 1973 every year 30,000 to 35,000 pelviscopies were registered in Germany; no deaths in 1974, 1976 and 1977.


New methods of pelviscopy (gynecologic laparoscopy) for myomectomy, ovariectomy, tubectomy and adnectomy. The development of suitable instruments for perfect grasping, cutting, sucking, ligating and of a new system of performing hemostasis by endocoagulation through a 7--11 mm phi trocar-sheath enables us to initiate effective endoscopical intraabdominal surgery. New surgical techniques are being investigated on greater than 2.000 cases of surgical pelviscopic interventions which were performed between 1973--1976. Since 1977 we have extended the endoscopical intraabdominal surgery as follows: Myomectomy (subserous), adnectomy, ovarian-cyst-resection, cystomectomy, tubectomy in case of tubal pregnancy. In 115 cases no intra- or postoperative complications have occurred. Normal postsurgical healing procedure could be checked on 18 re-pelviscopies and on 2 later laparotomies. The new technical equipment has opened us together with special surgical procedures a new era of gynecologic surgery.


Immune depression in trypanosome-infected mice. II. Characterization of the spleen cell types involved. Spleen cells from Trypanosoma congolense-infected mice showed a drastic depression in their capacity to respond to B and T lymphocyte mitogens and to allogeneic spleen cells in mixed lymphocyte cultures. Spleen cells from infected mice were also poor stimulators in mixed lymphocyte cultures. The poor responsiveness or stimulation capacity was not due simply to dilution of relevant B or T lymphocytes by the large number of null cells found in the spleens of infected animals. These null cells expressed approximately eight times more H-2 antigen than spleen cells from normal (uninfected) mice and were devoid of Ia antigens.


Immune depression in trypanosome-infected mice. III. suppressor cells. Spleen cells from trypanosome-infected mice strongly suppressed lymphocyte stimulation induced in normal spleen cell populations by lipopolysaccharide, concanavalin A or allogeneic (H-2-different) stimulator cells. This suppression was not H-2-restricted, as responses of spleen lymphocytes both allogeneic and syngeneic to the suppressors were inhibited. Irradiation or mitomycin C treatment of suppressor populations markedly reduced but did not eliminate suppressor activity. Suppressor populations were effective when present in very low numbers. Addition of suppressor cells to mixed lymphocyte cultures at various intervals after initiation of the cultures showed that the suppressors require 48 h to manifest their activity. Cell depletion or enrichment experiments indicate that the mechanism of suppression is complex and involves more than one cell type.


A histochemical study of denervated marsupial hemidiaphragm. The marsupial (quokka) hemidiaphragm showed postdenervation hypertrophy and subsequent atrophy. The type II muscle fibres hypertrophied up to 20 days postoperation and then regressed. However, the type I fibres hypertrophied throughout the experimental period (100 days) studied. Unlike denervated eutherian hemidiaphragm, fibre-splitting was absent in the denervated marsupial muscle. An enhancement of the ATPase reaction in the denervated type I fibres may be due to dedifferentiation. Presumably innervation exerts a 'negative control' and prevents increase of type I fibre size in the normal hemidiaphragm.


[Action of polymethylene-bis-quaternary compounds on the muscarinic and nicotinic cholinoreceptors]. The action of compounds with general formula (formula: see text) on the frog heart ventricle, cat blood pressure, guinea pig ileum and frog rectus abdominis was studied. With dioxolane radicals (type F-2268) a strong muscarinomimetic action on the cat arterial blood pressure and guinea pig ileum was observed, with maximum marked action at n = 10, which was more pronounced at an even than at odd number of methylene groups. On the frog heart the compounds with an odd number of "n" elicited an atropine-like action. The compounds with pentyl radicals produced no effect on blood pressure and a weak cholinolytic effect on the frog heart. On the ileum they exhibited a cholinomimetic effect. All compounds studied acted as noncompetitive cholinolytics on the frog rectus.


Saliva as a matrix for measuring free androgens: comparison with serum androgens in polycystic ovarian disease. We report a simple and direct procedure for the measurement of circulating free testosterone concentrations by using saliva as a matrix rather than serum. There is a close correlation between saliva testosterone values measured by radioimmunoassay, calculated values of free testosterone, and free testosterone estimated by equilibrium dialysis. Our method is direct and has the advantage that the biologic fluid can be obtained routinely by noninvasive techniques outside the clinic during a course of therapy. We also show that a single saliva value is of greater diagnostic use than any of the currently used androgen assays. Testosterone was found to be elevated in the saliva of 17 infertility patients diagnosed as having polycystic ovarian syndrome, 14 of these patients were hirsute.


Menstrual patterns and women's attitudes following sterilization by Falope rings. Follow-up data on 147 women sterilized by laparoscopic Falope ring application were analyzed for changes in menstrual patterns, postoperative complications, patient feelings about surgery, and incidence of regret. Twelve to twenty-eight months after surgery, there were no consistent changes in interval, length, or amount of menstrual flow, and only 4% of women developed transient episodes of dysfunctional uterine bleeding. Analysis of feelings after sterilization showed that 90% of women were satisfied with the sterilization, 3% were unhappy, and 7% were ambivalent. Feelings of regret were not associated with postoperative complications and appeared to be related to the reasons for sterilization. Individual counseling not only helped to identify the population at risk for regret but also served to reduce the incidence of poststerilization ambivalent feelings.


Erythroid differentiation and poly(ADP-ribose) synthesis in Friend leukemia cells. Nicotinamide, a specific inhibitor of poly(ADP-ribose) synthetase, was found to be a moderate inducer of hemoglobin synthesis in Friend erythroid leukemia cells (FLC). Therefore, the effect of other inducers, s-ch as dimethyl sulfoxide (DMSO), hexamethylene-bisacetamide (HMBA), and butyrate, on poly(ADP-ribose) synthesis was examined. The extent of poly(ADP-ribose) synthesis in nuclei of FLC treated with DMSO or HMBA began to decrease before many phenotypic changes including hemoglobin production and reached 30--50% of the level of nontreated control when the cells enter the stationary phase. FLC variants unresponsive to HMBA or DMSO did not exhibit as low an activity of poly(ADP-ribose) synthesis as their parent cells did by treatment with these inducers. In contrast, butyrate stimulated poly(ADP-ribose) synthesis transiently but distinctly (about 50%) at an early stage of culture (6--24 hr), but suppressed it at a later stage. Neither the cell growth nor degradation of poly(ADP-ribose) is correlated with the effect of inducers. These results suggest that the level of poly(ADP-ribose) synthesis is correlated with the differentiation of FLC.


Echocardiography: a diagnostic plus.

Echocardiography: a diagnostic plus. Echocardiography adds a new dimension to diagnosis of cardiac disorders. This safe, noninvasive technique aids in the differential diagnosis of systolic murmur, chest pain, and cardiomegaly, in the etiologic diagnosis of mitral regurgitation and atrial fibrillation, and in assessing left ventricular function.


Pyemotes herfsi (Oudemans, 1936) as causative agent of another mass dermatitis in Europe (Acari, Pyemotidae). The authors describe new cases of human dermatitis caused by Pyemotes herfsi occurring in the food mixing shed for the farrowing house in the piggery at a farm in the destrict of Olomouc, where seven persons handling feedstuff were infected. The disease became manifest as a papular rash, appearing particularly on the back, and all over the body except on the hands and face. When the afflicted person discontinued work in the feed mixing shed, the rash disappeared quickly. The mites were found in the granular dust accumulated in the loft above the food mixing shed. The initial host (insects) could not be identified. After cleaning and disinsecting the contaminated premises with Metation E 50 the workers were free from any symptoms. The mites of the genus Pyemotes, particularly the species P. herfsi (Oudemans, 1936) are little known, but probably frequent causative agents of human dermatitides.


[Hormonal regulation and hormone therapy in childhood and adolescence. Part 2: Therapeutic problems (tall stature, amenorrhea, delayed puberty, oligomenorrhea, precocious puberty, anorexia nervosa, anisomastia, hypermastia, acne etc)]. The most important therapeutic problems of female puberty and adolescence are discussed, including high stature, amenorrhoea, oligomenorrhea, pubertas tarda, anovulation, anorexia, anisomastia, hypermastia. Indications for treatment are given and the possibilities for a prophylactic medicine in this age group are stressed.


[Vascular reconstruction in the aorto-iliac region. Lowered mortality with an extraperitoneal approach]. From 1962 to 1978 1938 reconstructions because of arterial occlusive disease were performed at the Department of Surgery, Städt. Klinikum Karlsruhe. Of these 297 were primary aorto-iliac reconstructions. All latter cases were classified according to morphologic characteristics. The ratio of men to women was 8 : 1, the average age 58,9 years. A comparison of the results in these 227 patients with reconstruction either by endarteriectomy or dacron bypass was made regarding the way of incision. The results show a lower letality of 4,6% when extraperitoneal exposition is used compared to 14,1% when transperitoneal exposition was performed. As there was no difference found in the late results after either method of reconstruction (123 patients were reexamined), extraperitoneal exposition is preferred except in cases with aneurysm and aortic occlusion up to the renal arteries.


Loss of lymphocyte chalone activity in mice with autoimmune disease. Lymphocyte chalone from the spleens of old BALB/c, young BALB/c and young NZB mice caused significant suppression of the proliferative response of BALB/c and NZB spleen cells to T and B mitogens, whereas lymphocyte chalone from old NZB spleen did not suppress. Lymphocyte chalone from young and old NZB mice was tested using different ages of NZB/NZW responding spleen cells; at all ages concanavalin A- and lipopolysaccharide-induced proliferation was suppressed less by the chalone from old NZB mice than from that of young NZB mice. The responding NZB/NZW cells were suppressed equivalently at all ages studied. The basis for the loss of lymphocyte chalone activity in old NZB mice remains unknown; however, it appears likely that this event has a role in the disturbance of the negative feedback control system which contributes to NZB autoimmune disease.


Studies on the interference between the allergic reactions caused by different antigen-antibody systems. Interference between two different in vivo antigen-antibody reactions which occurred simultaneously was studied in guinea pigs. Animals were presensitized with an aqueous fraction (CP) extracted from cells of Corynebacterium equi, strain KO-85. Skin reactions of the Arthus type elicited by the CP fraction inhibited passive cutaneous anaphylaxis (PCA) induced by bovine serum albumin (BSA) and rabbit anti-BSA serum. PCA reactions of the CP-sensitized animals were also inhibited upon simultaneous challenges of BSA and the CP as evidence by reduction of PCA titer of the anti-BSA serum.


[Therapeutic aspects of seborrhea oleosa and pityriasis simplex capillitii]. The treatment of seborrhoea oleosa capillitii should aim at inhibiting depletion of the sebaceous glands, lipid synthesis in the sebaceous gland and microbial lipolysis of the triglycerides in the scalp and hair lipids. The use of isopropyl alcohol as a vehicle in a hair tonic reduces sebum depletion. Coal tar and estrogens reduce the lipid synthesis in the sebaceous gland. The lipolysis can be inhibited by various surfactants, isopropyl alcohol, colloidal sulphur, selenium disulphide, Omadine MDS and benzoyl peroxide. In the treatment of pityriasis simplex capillitii (dandruff) one aims at achieving inhibition of mitosis in the epidermis and, if possible, an additional "keratolytic" effect. Inhibition of mitosis could be demonstrated for coal tar, corticosteroids, selenium disulphide, cadmium sulphide, Omadine MDS, Zn Omadine and ichthyol sodium. Colloidal sulphur, salicylic acid, Omadine MDS and various surfactants act "keratolytically".


[Differentiation of various Propionibacterium species from acne-vulgaris efflorescences]. Samples of pustules taken from 37 patients with acne (a. vulgaris, a. papulopustulosa, a. conglobata) were examined using different culture mediums for the growth of anaerobic to microaerophilic coryneforms. We identified 46 isolates of Propionibacteria which were tested according to their morphological, biochemical, serological, and phagelysotopic reactions. Three types of Propionibacteria were found: P. acnes (33), P. granulosum (11) and P. avidum (2). Nine samples showed P. acnes combined with P. avidum, four samples from patients with acne conglobata showed P. granulosum or P. avidum only. Tests from 37 patients are too limited to reach definite conclusions. We are not able to suggest any correlation between type and degree of clinical acne, and the isolated Propionibacteria. These data indicate that pustules from patients with acne of all clinical degrees can contain P. acnes as well as other anaerobic coryneforms. Therefore, other species of anaerobic bacteria, particularly those of the "propionibacteria type", should be included in any discussion about the aetiological factors of acne.


Comparison of inducible and constitutive kynureninases of Neurospora crassa. Two types of kynureninase were isolated from Neurospora crassa IFO 6068. The formation of one of them, which was separated from the inducible kynureninase by DEAE-cellulose chromatography, was independent of the presence of tryptophan in the growth medium. Ouchterlony double-diffusion analysis and immunochemical titration indicated that the constitutive-type enzyme is immunologically different from the inducible enzyme. We confirmed by a selective assay method with antiserum that the addition of tryptophan to the medium does not affect the formation of one of the enzymes (constitutive-type). The constitutive kynureninase was purified approximately 650-fold and was free of the inducible enzyme as judged by analytical gel electrophoresis. The molecular weight and optimum pH values of both enzymes are very similar. However, the constitutive enzyme shows much higher activity and affinity for L-3-hydroxykynurenine than for L-kynurenine, suggesting that the enzyme functions biosynthetically as a 3-hydroxykynureninase. Constitutive kynureninase activities were widely found in all the fungi tested, whereas the inducible enzyme activity was not present in Mucor or Rhizopus species. The inducible enzymes of all the Neurospora strains examined were shown to be immunologically identical.


Effect of thymidine on poly(ADP-ribosyl)ation in vivo. The addition of thymidine as well as nicotinamide to isolated nuclei resulted in a strong inhibition of poly(ADP-ribosyl)ation, whereas that of hydroxyurea and amethopterin has essentially no effect. The nuclei isolated from the cells immediately after release from thymidine synchronization exhibited a significantly increased activity of poly(ADP-ribosyl)ation. Thereafter, the fluctuation pattern of the activity of poly(ADP-ribosyl)ation in isolated nuclei during the cell cycle was essentially the same as in the case of hydroxyurea synchronization. The activity of poly(ADP-ribosyl)ation in isolated nuclei after treatment with thymidine in vivo increased with the treatment time. The time-dependent increase was also evident in the case of nicotinamide treatment. Little increase in the activity was observed in hydroxyurea and amethopterin treatment. When poly(ADP-ribose) polymerase was extracted from the nuclei isolated from the cells which were pretreated with each of the four compounds, there was no significant difference in the amount among these compounds. The reason for the increase in the poly(ADP-ribosyl)ation in vitro by the in vivo treatment with thymidine is discussed.


Size and molecular parameters of adenosine triphosphatase from Escherichia coli. The Mg2+- and Ca2+-stimulated ATPase (bacterial coupling factor) has been investigated in solution with different independent techniques. The molecular weight of the five-subunit enzyme was found to be 345,000 +/- 5,000 by means of light scattering, 350,000 by sedimentation equilibrium experiments, and 358,000 by means of small-angle x-ray scattering. The radius of gyration was found to be 41.9 A, the volume 7.39 x 10(5) A3, and the surface to volume ratio 5.5 x 10(-2) A-1 from small-angle x-ray scattering measurements of the enzyme in solution. The degree of hydration was found to be 0.62 ml of H2O/g of ATPase. The translational diffusion coefficient was determined to be 3.47 x 10(-7) cm2 s-1 by means of inelastic light scattering. The distribution of the scattered intensity near the origin appears to be bimodal, suggesting that the ATPase molecule is composed of spherical parts bound together by a flexible polypeptide chain. The largest dimension of the ATPase in solution is 120.0 A, determined from the pair distribution function.


Inactivation of phosphofructokinase by glucagon in rat hepatocytes. Kinetic evidence of a time- and dose-dependent inactivation of phosphofructokinase by glucagon in isolated rat hepatocytes is reported. This inactivation, which persists after gel filtration of a cell-free extract on Sephadex G-25 and after 400-fold purification of the enzyme on agarose-ATP, is observed when the enzyme activity is measured at subsaturating concentrations of fructose 6-phosphate, while there is no change in Vmax. Phosphofructokinase inactivation by glucagon parallels the known inactivation of pyruvate kinase L and activation of glycogen phosphorylase alpha. Exogenous cyclic AMP mimics the effect of this hormone. Half-maximal effect for both phosphofructokinase and pyruvate kinase L is caused by a similar dose of glucagon (1 x 10(-10) M). The inactivation of phosphofructokinase by nonsaturating concentration of glucagon is reversed spontaneously within 40 min of incubation and this reversion is accelerated by insulin.


The effect of ionomycin on calcium fluxes in sarcoplasmic reticulum vesicles and liposomes. Ionomycin, a recently discovered calcium ionophore, inhibits the ATP-dependent active Ca2+ transport of rabbit sarcoplasmic reticulum vesicles at concentrations as low as 10(-8) to 10(-6) M. The effect is due to an increase in the Ca2+ permeability of the membrane which is also observed on liposomes. The inhibition of Ca2+ uptake is accompanied by an increase in the Ca2+-sensitive ATPase activity of sarcoplasmic reticulum vesicles.


Purification and reconstitution of the Ca2+-ATPase from plasma membrane of pig erythrocytes. The Ca2+-ATPase from plasma membranes of pig erythrocytes was purified by mixed micelle gel chromatography (Wolf, H.U., Diekvoss, G., and Lichtner, R. (1977) Acta Biol. Med. Germ. 36, 847-858). The enzyme was activated at high concentrations of Tween 20 (10 mg/ml) or by appropriate mixtures of Triton X-100 and phospholipids. It was highly unstable in the absence of Ca2+ and activator protein. The Ca2+-ATPase was incorporated into liposomes by freeze-thaw sonication. After removal of non-ionic detergent by passage through a phenyl Sepharose 4B column, the reconstituted vesicles catalyzed a rapid ATP-dependent uptake of Ca2+. Modulator protein from brain substituted for the natural activator protein and stimulated Ca2+ uptake in reconstituted vesicles.


Seventy-two hour infusions of LHRH in normal men: gonadotropin and testicular steroid responses. Four normal male subjects received LHRH by continuous infusion for 72 hrs at 1.4 microgram/min. Mean basal LH was 7.7 +/- 1.0 mIU/ml, increased to a maximum of 120 +/- 22.7 mIU/ml, and then declined to levels between 28--34 mIU/ml for the last 30 hrs of infusion; FSH rose from 3.7 to 11.4 mIU/ml (p less than 0.05) at 16 hrs and then returned to baseline. Testosterone levels rose by 50% at 12 hrs, and remained elevated throughout with maximum values between 6.6 and 12 ng/ml. Estradiol-17beta levels were 26.2 +/- 4.7 pg/ml basally, rose to 104 +/- 8 pg/ml and while levels declined therafter, they were significantly above baseline throughout the 72 hrs. Plasma androstenedione and dehydroepiandrosterone levels also showed significant increases. By contrast, transient elevations in pregnenolone and 17-hydroxypregnenolone levels probably corresponded to the nomral morning rise in plasma levels of these steroids; 17-hydroxyprogesterone rose from 1.3 +/- 0.15 to 3.9 +/- 0.26 ng/ml at 12 hrs and remained elevated through the infusion. An increase in 17-hydroxyprogesterone:testosterone ratio was observed in all subjects. Thus, chronic LHRH infusion effected a persistent increase in endogenous LH with, in turn, prolonged stimulation of gonadal steroid secretion.


Interrelationships of circulating maternal steroid concentrations in third trimester pregnancies. III. Effect of intravenous cortisol infusion on maternal concentrations of estriol, 16 alpha-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, progesterone, 20 alpha-dihydroprogesterone, delta 5-pregnenolone, delta5-pregnenolone sulfate, dehydroepiandrosterone sulfate, and cortisol. The effect of a large dose (1000 mg) of iv cortisol-hemisuccinate on circulating steroid concentrations in five women, 28--34 weeks, gestational age, is reported. Maternal concentrations of estriol, 16 alpha-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, progesterone, 20 alpha-dihydroprogesterone, delta 5-pregnenolone, delta 5-pregnenolone sulfate, dehydroepiandrosterone sulfate, and cortisol were measured by RIA before and at 8 and 12 h after iv cortisol infusions at 0 and 8 h. Data were evaluated by repeated measure analysis of variance. Estriol and 17 alpha-hydroxyprogesterone suppressed initially (P less than 0.05) and suppressed further with retreatment and increased treatment time (P less than 0.05). Dehydroepiandrosterone sulfate and progesterone suppressed initially (P less than 0.05) but did not suppress further with retreatment and increased treatment time (P greater than 0.05). delta 5-Pregnenolone and delta5-pregnenolone sulfate increased initially (P less than 0.05) but did not increase further (P greater than 0.05). Concentrations of 16 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone were unchanged by cortisol infusion initially (P greater than 0.1) and with retreatment and increased treatment time (P greater than 0.1).


Congenital deficiency of alpha 2-plasmin inhibitor associated with severe hemorrhagic tendency. alpha(2)-Plasmin inhibitor (alpha(2)PI) is a recently characterized, fast-reacting plasmin inhibitor in human plasma that appears to play an important role in regulation of in vivo fibrinolysis. We report here a case of complete deficiency of alpha(2)PI in man. The patient, a 25-yr-old Japanese man, had a life-long severe bleeding tendency (hemarthrosis and excessive bleeding after trauma). The following tests were within normal limits: platelet count, bleeding time, thrombin time, prothrombin time, partial thromboplastin time, titers of known clotting factors, platelet glass bead retention, Factor VIII-related antigen, platelet aggregation by ADP, collagen and ristocetin, and clot retraction. Routine liver function tests were also normal. The only abnormal finding was that whole blood clot lysis was extemely rapid and was complete in 4-8 h. The concentration of plasma protease inhibitors, including alpha(2)-macro-globulin, antithrombin III, alpha(1)-antitrypsin, and C1INH, were all normal. The concentration of alpha(2)-PI in the patient's plasma, assayed by immunological methods, was <0.1 mg/100 ml (normal concentration, 6.1+/-0.88 mg/100 ml [mean+/-SE]) and functional assays showed a complete deficiency of alpha(2)PI. Addition of purified alpha(2)PI to the patient's whole blood completely corrected the accelerated fibrinolysis. The patient's parents, four siblings, and four other members of this family were asymptomatic, but the titers of alpha(2)PI in their plasmas were congruent with50% of normal pooled plasma. There were three consanguineous marriages in this family, and the alpha(2)PI deficiency appears to have been inherited as an autosomal recessive trait. We speculate that alpha(2)PI deficiency in this patient has led to uninhibited in vivo fibrinolysis that probably causes the severe hemorrhagic tendency. Thus, this study indicates the important role of alpha(2)PI in hemostasis.


Inhibition of humoral and cell-mediated immune responses in man by distinct suppressor cell systems. Studies were designed to investigate whether the suppressor cell systems that regulate the humoral and cell-mediated immune responses belong to the same subsets of T cells or different subsets. Mitogen-activated suppressor cells were simultaneously assayed for their ability to inhibit (a) pokeweed mitogen-induced generation of plasma cells, (b) blastogenic response of lymphocytes to allogeneic cells, and (c) generation of killer cells in the cell-mediated lymphocytotoxicity assay. We found that suppressor cells that inhibited the generation of plasma cells were activated by concanavalin A (Con A) and were both radiation and prednisone sensitive. Suppressors that inhibited the blastogenic response in lymphocytes to allogenic cells were also activated by Con A but differed in that they were both radiation and prednisone resistant. In contrast, suppressors that inhibited the generation of the killer cells were activated with phytohemagglutinin and not Con A. These suppressors were prednisone and radiation resistant. These observations cannot be explained by differences at the pro-suppressor or suppressor activator levels as both T cell subsets are radiosensitive. Alternatively, heterogeneity of suppressor cell systems may explain these differences.


Suppression of acute and chronic inflammation in tumor-bearing rats. Both acute and chronic cellular inflammatory reactions were suppressed in rats bearing malignant tumors. Inhibition of the acute inflammatory reactions was demonstrated in immune complex-induced vasculitis and in the accumulation of leukocytes in subcutaneously implanted polyvinyl sponges. Suppression of chronic inflammatory reactions was demonstrated in delayed type hypersensitivity skin reactions. In spite of these suppressed reactions, dermal reactivity to vasopermeability mediators was not diminished. Neither serum complement levels nor numbers of circulating leukocytes were depressed in animals with tumors. Suppression of inflammatory reactions was paralleled by a leukotactic defect which involved both neutrophils and monocytes. This defect could be ascribed to an abnormality in the serum that rendered both cell types leukotactically defective.


Stress reactions of various judging groups to the child dental patient. Dental personnel representing various levels of clinical experience and education in pedodontics were shown slides of potentially stressing situations within the field of pedodontics. Stress was identified through voice analysis by the Psychological Stress Evaluator (PSE-101). Clinical experience and education in pedodontics does not decrease either absolute or relative amounts of stress. Visual stimuli are capable of eliciting a stressful response. Trained raters can interpret voice prints with a satisfactory degree of inter-rater reliability. The PSE-101 is a valid indicator of stress.


Effect of indomethacin on Ca2+-stimulated adenosine triphosphatase in the microsomes of rat submandibular gland. The effect of indomethacin, which is a nonsteroidal anti-inflammatory drug, on Ca2+-stimulated adenosine triphosphatase (Ca2+-ATPase) activity in the microsomes of rat submandibular gland was investigated. The effect of aspirin on Ca2+-ATPase activity was also studied.


Histochemical comparison of focal losses of RNase and ATPase activities in preneoplastic rat livers. To better assess the significance of enzyme-deficient foci as putative premalignant lesions, parallel histochemical analyses of RNase and ATPase activities were carried out in serial sections of livers from rats fed 4-dimethylaminoazobenzene. The results showed that focal losses of RNase and canalicular ATPase activities occur simultaneously in congruent areas of liver parenchyma at early stages of carcinogenesis. Such foci presumably represent altered cells capable of progressing to neoplasia since the changes observed in this new cell population persist in developing tumors.


Physiology of mixed leukocyte reaction suppressor factor. I. Role of cytoskeleton and protein synthesis in production and secretion. The secretory physiology of the T cell-produced lymphokine, mixed leukocyte rection suppressor factor (MLR-TsF), was characterized with respect to its kinetics of secretion and its sensitivity ot a variety of metabolic blocking agents. It was found that spleen cells from alloantigen-immunized mice released active MLR-TsF after freeze-thaw lysis. Upon restimulation with the same priming alloantigen, MLR-TsF was secreted into culture supernatants, and the rate of secretion was determined to be nearly constant. Although colchicine and vinblastine, which bind to microtubules, are known inhibitors of lectin-induced proliferation, it was demonstrated that these drugs had no effect on the secretion of MLR-TsF. However, cytochalasin B, an inhibitor which also binds to some cytoskeletal and membrane-associated proteins, did inhibit the production of MLR-TsF. The above findings indicated that the activation-secretion mechanism of of MLR-TsF was much like that described for lymphotoxin and macrophage migration inhibition factors. The dissociation between DNA synthesis and lymphokine secretion was also demonstrated in the MLR-TsF system. DNA synthesis plays no role in the in vitro production of suppressor factor, as determined by resistance to treatment with mitomycin C and gamma-irradiation. However, new protein synthesis is required as indicated by the potent inhibitory effects of cycloheximide. Experiments utilizing timed addition and removal of cycloheximide defined a broad period of drug sensitivity, starting from the beginning of culture and lasting for 12 to 16 hr. In addition, experiments measuring the effect of cycloheximide on the MLR-TsF content of cell lysates demonstrated that the cell-associated lymphokine activity is lost when protein synthesis is interrupted. These experiments support the conclusion that MLR-TsF is synthesized de novo in culture. In addition, the secretory process itself may require protein synthesis.


Human macromolecular insoluble cold globulin (MICG). II. Immunologic definition of T cell and null cell MICG and the biologic effect of antiserum to MICG. Thymus cell-derived macromolecular insoluble cold globulin (T-MICG) is a 225,000-dalton protein, selectively synthesized in human T cells. Null cell-derived macromolecular insoluble cold globulin (N-MICG) is a 185,000-dalton protein, synthesized in null cells, and antigenically distinct from T-MICG. Evidence to support these conclusions was provided by using isolated cell preparations that were radiolabeled, lysed in desoxycholate, and precipitated with monospecific antiserum to each component. These studies demonstrated that antiserum to T-MICG precipitated a 225,000 dalton protein from PBL and T cells, but not from B or null cells. Antiserum to N-MICG reacted with a 185,000 dalton protein present in PBL and null cells, but not with lysates from either T or B cells. The plasma membrane distribution of these proteins was shown by absorption of antiserum to T + N-MICG with either isolated T or null cells. Antibody-induced cytotoxicity and immunofluorescence confirmed the cell surface location of T and N-MICG. Divergent biologic effects of these antisera were also noted. Antiserum to T-MICG inhibited T cell rosette formation and the one-way mixed lymphocyte reaction, although anti-N-MICG antiserum had no such effect. The potential importance of these proteins is discussed.


Macromolecular insoluble cold globulin (MICG): a novel protein from mouse lymphocytes. III. Relationship to the mixed lymphocyte reaction and effect of anti-MICG antiserum in vivo. In the present communication we have examined the relationship between the synthesis of macromolecular insoluble cold globulin (MICG) and the mixed lymphocyte reaction (MLR). In addition, we have studied in vivo the effect of antiserum to MICG on the antibody response to sheep red blood cells. The experiments indicate that MICG synthesis compared to either IgM or total protein is selectively stimulated in responder T cells exposed to allogeneic stimulator cells in the MLR. Furthermore, cytotoxicity studies utilizing anti-MICG antiserum demonstrated that T cells bearing MICG on their surface are an essential component of the responder cell population in the MLR. In vivo administration of antiserum to MICG significantly suppressed both the primary and secondary antibody response to sheep red blood cells. A possible mechanism for this suppression is discussed.


Inhibition of T cell-mediated cytolysis by 2-deoxy-D-glucose (2-DG): differential effect of 2-DG on effector cells isolated early or late after alloantigenic stimulation in vitro. The effect of the hexose analogue 2-deoxy-D-glucose (2-DG) on the functional activity of various populations of cytolytic T lymphocytes (CTL) has been compared. Under aerobic conditions, CTL harvested at the peak of the response (day 4) in primary or secondary mixed leukocyte cultures (MLC) were much more readily inhibited by 2-DG that CTL obtained from MLC at later times (day 11 to 18) or from the peritoneal cavity of alloimmune mice. Quantitatively, 0.4 mM 2-DG was sufficpient to inhibit cytolysis by 50% in day 4 CTL populatons, whereas 25 mM had little or no effect on day 11 to 18 CTL. Evidence was obtained that inhibition of cytolysis by 2-DG under these conditions was accompanied by a parallel inhibition of effector:target cell binding. In contradistinction to these findings, the cytolytic activity of both day 4 and day 11 MLC cells was readily inhibited by 2-DG under conditions where cell respiration was blocked by sodium azide. Furthermore, uptake of radiolabeled 2-DG was observed under aerobic conditions in both day 4 and day 11 MLC cells. These results strongly suggest that inhibition of cytolysis by 2-DG under aerobic conditions is mediated via a direct effect on CTL which is independent of the consequences of energy depletion. An indirect method by which CTL may be inhibited by 2-DG is suggested.


Suppression of cell-mediated immune reactions by monosaccharides. Various monosaccharides have been shown capable of inhibiting lymphokine activity in in vitro assay systems. In this study, we demonstrate that L-fucose can inhibit the ability of lymphokine-containing supernatants to induce skin reactions or cause reductions in the macrophage content of peritoneal exudates. Moreover, L-fucose can inhibit the cutaneous delayed hyoersensitivity reaction and the peritoneal macrophage disappearance reaction (MDR) induced by antigen in actively immunized guinea pigs. The effect of L-rhamnose, another sugar with in vitro inhibitory activity, was investigated in the MDR, and was also shown to be inhibitory. L-arabinose, which has no in vitro effects on lymphokines, had no suppressive effect on any of the in vivo systems studied. No monosaccharide inhibition of Arthus reactions or nonspecific inflammation could be found in these studies. The results demonstrate that monosaccharides capable of inhibiting lymphokine activity in vitro are effective in suppressing in vivo manifestations of cellular immunity.


Con A-inducible suppression of MLC: evidence for mediation by the TH2 + T cell subset in man. Human peripheral lymphoid cells pretreated with Concanavalin A for 48 hr can markedly suppress the proliferative response of untreated autologous lymphoid cells in MLC. Isolation studies with Sephadex G-200 anti-F(ab')2 affinity chromatography, nylon adherence, and E rosetting indicate that the Con A-induced suppressor cell is a T cell. Further fractionation into TH2+ and TH2- cell subsets with an equine-anti TH2 serum show that both subsets can be activated by Con A to an equivalent degree. After activation only the TH2+ subset can suppress autologous responder cells in MLC. The TH2- subset, which comprises 80% of peripheral human T cells, although induced by Con A to proliferate, cannot itself suppress the MLC response. Nevertheless, the TH2- subset can be shown to modulate the generation of suppressor TH2+ cells at 24 hr but not at 48 hr. These studies support the notion that the Con A-induced suppressor cell is confined to a distinct T cell subset in man and that T-T interactions are important in the overall expression of the immune response.


Regulatory T cell subpopulations in pregnancy. I. Evidence for suppressive activity of the early phase of MLR. Previous in vivo experiments have provided evidence of suppressive activity induced by multiple allogeneic pregnancies. The reactivity of maternal spleen cells toward paternal strain alloantigens was investigated by use of MLR microculture technique. A study of the kinetics of the MLR showed an early peak of reactivity (48-hr culture) followed by a decline leading to a decreased reactivity by 96 hr when spleen cells from allogeneically pregnant mice were compared to those of virgin or even isogeneically pregnant mice, suggesting the possible action of MLR regulatory cells. A strong suppression of a H-2k (CBA) anti-H-2a (A/J) or anti-H-2d (C57BL/Ks) MLR was observed when mitomycin-treated spleen cells from CBA mice multiparous by A/J or C57BL/Ks (but not CBA) males were added to the culture. This suppression was abolished by treating the regulatory cell population with anti-theta serum plus complement or replacing the 1% normal mouse serum in the medium by a proper antiidiotypic mouse serum.


Studies of the mechanisms for the induction of in vivo tumor immunity. IV. Enhancement of the in vitro generation of secondary cell-mediated cytotoxic response by normal peritoneal macrophages and their culture supernatants. The effect of macrophages on the induction of the cell-mediated cytotoxicity against a leukemia in a syngeneic system was investigated. The addition of exogenous peritoneal cells from normal C57BL/6 MIce enhanced the in vitro secondary cell-mediated cytotoxic response of both spleen and lymph node cells as responding cells against syngeneic FBL-3 leukemia. Peritoneal phagocytic macrophages seemed to be responsible for the enhancement. No inhibitory effect was demonstrated by the addition of peritoneal macrophages at a concentration as high as 20%, whereas the primary cytotoxic allograft response was significantly suppressed. In the present studies, there was no absolute restriction of macrophage-T cell interaction by an H-2 barrier. Supernatants of peritoneal macrophage cultures also enhanced this cell-mediated cytotoxic response. There was no difference between the effects of syngeneic or allogeneic peritoneal macrophage culture supernatants.


DRw antisera react with activated T cells. Nylon wool-purified T cells appear to be nonreactive in a lymphocytotoxicity assay with HLA-DRw antisera and complement before cell activation. However, after activation in mixed lymphocyte culture, responder cells express determinants that are strongly reactive with DRw alloantisera after 6 days and gradually disappear by 16 to 18 days. Restimulation of the primed cells resulted in re-expression of the blast determinants. Mitogenic stimulation with Con A or purified PHA (HA-17) also resulted in temporary expression of these determinants; reactivity usually conformed to DRw genetic restriction; however, occasional extra reactions occurred that were variable depending on the method of activation (i.e., MLC, Con A, or HA-17). The results suggest the presence of additional allospecificities within some of the DRw antisera that react with "Ia-like" antigens on activated cells from unique subsets of T cells. Whether these DRw antisera contain antibodies against T cells or agains activation or differentiation T cell antigens is not as yet clear.


Lung tumor-reactive cytotoxic lymphocytes generated in mixed lymphocyte reaction between C3HfeB/HeN (H-2kb) and C3H/HeN (H-2k) strain mice. The tumor-associated transplantation antigen expressed by several transplacentally induced lung tumors of C3HfeB/HeN mice (H-2kb haplotype) has previously been shown to exist as a normal tissue alloantigen in mice of known H-2k and H-2a haplotypes. This antigen is not expressed in normal tissues of C3HfeB/HeN mice but is expressed in C3H/HeN mice, the strain from which the C3HfeB/HeN mice were originally derived. The present study indicates that spleen cells from C3HfeB/HeN and C3H/HeN mice respond reciprocally in the mixed lymphocyte reaction. Cytotoxic T lymphocytes specific for the tumor-associated alloantigen can be readily generated in mixed lymphocyte reactions in which spleen cells from C3HfeB/HeN mice are reacted with x-irradiated spleen cells from C3H/HeN or A strain mice. These cells are effective in suppressing the growth of the C3HfeB/HeN-derived lung tumor 85 in x-irradiated syngeneic recipients.


Amplification of the proliferative response to alloantigen by a factor present in an extract of syngeneic thymic lymphoid cells: demonstration of optimal conditions and target cell for factor activity. A factor extracted from syngeneic thymic lymphoid cells (thymocytes) is shown to amplify the proliferative (MLC) response of syngeneic lymphoid cells to alloantigen in vitro. The optimal conditions for an effect of the thymus factor are quantitatively defined by kinetic and dose-response studies. Other variables that could potentially influence the activity of the thymus factor, such as the presence of 2-mercaptoethanol and the source of alloantigen, are identified. Factor activity can be recovered from semi-allogeneic thymocytes, as well as syngeneic thymocytes. The factor appears to predominantly effect the proliferative response of T cells localized in peripheral lymphoid organs. As such, this factor appears to be distinct from the variety of previously described factors derived from thymic reticuloepithelial elements that are thought to primarily induce the differentiation of T cell precursors found predominantly in bone marrow. Several possible mechanisms of action of this thymocyte-derived factor are considered.


Induction of autoreactive cells by the preculture of human peripheral blood mononuclear cells with the autologous fresh plasma. An AMLR in which precultured cells proliferated in response to fresh non-T cells is described. In our system, the responder is human peripheral blood mononuclear cells precultured in the autologous fresh plasma for up to 16 days, and the stimulator is fresh autologous non-T cells. Results suggested that there were two subpopulations of autoreactive cells obtained from the preculture; the high and low density small lymphocytes, both having ERF activity. The autoreactivity of low density cells was augmented when either macrophages or N-ERF-cells were depleted from PBM and thereafter precultures wre performed. A survey of the functional characteristics of the responding cells showed that the responding cells had NK activity against Molt-4 cells but had no significant ADCC activity against target CRBC. Mechanisms for the induction of autoreactive cells by the preculture in the presence of autologous fresh plasma are discussed.


The differentiation of cytotoxic T cells in vitro. I. Amplifying factor(s) in the primary response is Lyt 1 + cell dependent. Within 15 hr of establishment of a murine mixed lymphocyte culture, a soluble mediator was produced that was capable of augmenting primary cytotoxic responses to alloantigen. The factor did not induce responsiveness in the absence of antigen, since the amplified response seen in its presence was specific for the stimulating alloantigen. The factor did not therefore appear to function by polyclonal activation of cytotoxic precursor cells. Production of the amplifying factor(s) was induced by unfractionated spleen cells, but not by cells subjected to UV irradiation or to sonication, making it likely that this deficiency is the basis of the well-documented failure of these stimulator cells to induce primary cytotoxic responses. The amplifying effects of the factor were distinctive from, but synergistic with, those of 2-mercaptoethanol. Production of the amplifying mediator did not require cell division but was dependent upon the presence of Lyt 1 + cells. On the other hand, Lyt 2 + cells were not needed for mediator production, but served as target cell population on which the factor exerted its action. These findings are compatible with the hypothesis that direct T-T cell collaboration can amplify the differentiation of cytotoxic cells.


Isolation and characterization of actin and myosin from B-lymphocytic guinea pig leukemia cells. Actin and myosin have been isolated from a guinea pig B cell leukemia line, L2C. The m.w. and amino acid compositions of these proteins are similar to actin and myosin from other nonmuscle cell types. L2C actin polymerizes to form filaments and activates the ATPase activity of skeletal muscle myosin. Actin in crude lymphocyte extracts does not polymerize as well as predicted from the critical concentration of purified lymphocyte actin suggesting that other factors in lymphocyte extracts regulate actin polymerization. Lymphocyte myosin polymerizes to form synthetic filaments at low ionic strength. Lymphocyte myosin binds to actin, but its ATPase activity is not activated by actin. Possible mechanisms for regulation of the lymphocyte contractile apparatus and its importance in a number of lymphocyte functions are discussed.


Limiting dilution analysis of alloantigen-reactive T lymphocytes. III. Effect of priming on precursor frequencies. The effect of specific priming with alloantigens on the frequency of cytolytic T lymphocyte precursors (CTL-P) has been investigated. Alloimmune lymphoid cells were obtained from the spleen of C57BL/6 (H-2b) mice primed with DBA/2 (H-2d) tumor cells or from 14-day unidirectional mixed leukocyte cultures (C57BL/6 anti-DBA/2). CTL-P frequencies directed against H-2d alloantigens were estimated by limiting dilution analysis in a sensitive micro MLC system. Under these conditions, an apparent increase of 3 to 4-fold in CTL-P frequency was observed in alloimmune (as compared with normal) C57BL/6 spleen cells. Evidence was obtained suggesting that this increase was specific for the priming alloantigens. A much greater increase in CTL-P frequency (25 to 100-fold) was observed after alloimmunization of C57BL/6 spleen cells in unidirectional MLC. Under the latter conditions, 5 to 20% of the surviving splenic MLC cells could be identified operationally as CTL-P. A similar enrichment in CTL-P frequency was obtained when lymph node, peripheral blood, or thymus cells were cultured for 14 days in MLC. These studies provide direct evidence that the pool of specific CTL-P can be expanded after alloimmunization. Furthermore, the very high frequencies observed after in vitro priming indicate that this system should be particularly useful for future studies of the progeny of individual CTL-P.


Inhibition of the mixed lymphocyte reaction by fractionated niridazole urine dialysate. Urine dialysate from rats treated orally with 25 mg/Kg 3H-labeled niridazole was fractionated by DEAE-Sepharose column chromatography and was found to contain three radioactive metabolites and no parent compound. When human niridazole urine dialysate (NUD) was fractionated under identical conditions, fractions corresponding to the three rat NUD metabolites were found to inhibit the human one-way MLR. No inhibition was obtained with fractionated control urine dialysate. It was concluded that nonimmunosuppressive niridazole is metabolized by rats and man to produce three active compounds with the ability to suppress the in vitro response to alloantigens.


Surface properties and in vitro functional capacities of human T lymphocyte subsets separated by linear density gradients. Human lymphocytes derived from various central and peripheral sources were separated on linear density gradients (LDG). Cells from individual density fractions were tested in parallel for: the capacity to form nonimmune rosettes with neuraminidase-treated SRBC, the number of surface-associated HTLA, and in vitro proliferative responses to mitogenic lectins and alloantigens. Heterogeneous density distribution profiles were obtained for all sources of human T cells and revealed an organ specificity. The various T cell density classes obtained from identical organs as well as the identical density classes of different sources revealed to some extent differences in their surface marker patterns and/or their in vitro reactivities. On the basis of the combined techniques at least two major subsets among thymocytes were identified that differed in both surface properties and functional capacities. Density classes of T cells from all peripheral sources were distinguished from thymocytes by a homogeneous lowered HTLA expression. Whereas clear-cut differences in the in vitro functional capacity were observed between the two thymocyte subsets, less striking but still significant differences were found to exist among the various density classes of peripheral T cells.


Activation of suppressor T cells in human autologous mixed lymphocyte culture. Co-culture of autologous T and mitomycin-C treated B cells results in increased DNA synthesis in the responding T cells. T cells thus activated in AMLC exerted suppressive effects on both the proliferative and cytotoxic responses of fresh unstimulated T cells to allogeneic cells in MLC. The suppressor cells generated are sensitive to treatment with mitomycin-C. AMLC-activated cells treated with mitomycin-C failed to suppress both cytotoxicity and proliferation in fresh primary MLC. It appears that the AMLC reaction reflects an immunologic homeostatic mechanism. Since this reaction is defective in patients with CLL and SLE and the homologous mouse syngeneic MLC is defective in NZB mice, the failure of this T-B interaction may be related to the pathogenesis of certain lymphoproliferative and autoimmune disorders.


The in vitro generation and sustained culture of nude mouse cytolytic T-lymphocytes. In addition to allowing for the long-term culture of both murine and human cytolytic T lymphocytes, T-cell growth factor (TCGF) functions as the key proliferation-inducing second signal in both T-cell antigen sensitization and mitogenesis. The observation that thymocytes responded normally to T-cell mitogens in the presence of TCGF, prompted the investigation of the effect of TCGF on nude mouse lymphocyte responses in vitro. We found that spleen, lymph node, and bone marrow cells, isolated from nude mice, were incapable of producing TCGF yet responded normally to T-cell mitogen sensitization provided stimulation was conducted in the presence of TCGF. Nude mouse spleen cells were also capable of responding to alloantigen sensitization in mixed lymphocyte cultures (NLMC) conducted in the presence of TCGF. Thy-1 antigen-positive cells harvested from TCGF-supplemented nude mouse MLC effectively mediated the cytolysis of alloantigen-specific target cells as tested in standard 51Cr-release assays. Cytolytic nude mouse effector cells have remained in TCGF-dependent culture for over 3 mo during which they have continued to mediate significant levels of alloantigen-specific cytolytic reactivity. These results suggest that prothymocytes present in nude mice are capable of responding to immunologic stimuli by differentiating, in vitro, into cytolytic T lymphocytes and that furthermore, a major function of the thymus may be to effect the maturation of TCGF-producing cells.


Induction of polyclonal antibody synthesis by human allogeneic and autologous helper factors. Human helper factors were obtained from supernates of 48 h unidirectional allogeneic and autologous mixed lymphocyte reactions. These supernates were shown to induce the production of large amounts of immunoglobulin by tonsillar and peripheral blood mononuclear cells. Abundant polyclonal activation to antibody production occurred in these cultures in the absence of antigenic challenge which was similar in degree to that produced by pokeweed mitogen. This was documented by quantitating plasma cells, specific plaque-forming cells, and secreted immunoglobulin. In addition, the supplementation of companion cultures with sheep erythrocytes resulted in a significant enhancement of the specific plaque-forming cell response without an appreciable change in plasma cell number of secreted Ig.


Dermatoses of the scalp.

Dermatoses of the scalp. By judicious consideration of the clinical appearance, by direct examination with magnification, and by culture results, skin biopsy, and other laboratory results, the clinician is able to diagnose most pathological conditions of the scalp. The scalp participates in many systemic disorders and frequently is the chief site of involvement. Similarly, many generalized disorders limited to the skin exhibit their most typical manifestations in the scalp. Whenever a diagnosis eludes the investigator, more than likely he or she has not considered all of the etiological possibilities or has not pursued an adequate laboratory investigation. A few scalp diseases initially present nonspecific clinical pictures. By utilizing follow-up examinations at appropriate intervals, the diagnosis can eventually be made. Once a diagnosis is made, appropriate treatment will generally produce satisfactory improvement or cure. Nevertheless, a few generally rare conditions will defy the physician's most enlightened and aggressive therapy.


Mutagenicity and mutagenic specificity of metronidazole and niridazole in Neurospora crassa. Mutagenicity and mutagenic specificity of niridazole and metronidazole, two chemotherapeutic agents used in the treatment of human parasitic diseases, were studied with the ad-3 test system of Neurospora crassa. The results show that neither compound is mutagenic in resting conidia. In growing vegetative cells, however, both compounds are mutagenic in Neurospora crassa. Genetic analysis of the mutants indicate that niridazole induces predominantly base-pair substitution mutations. None of the niridazole-induced mutants resulted from multilocus deletions. The spectra of genetic alterations induced by metronidazole are similar to those induced by the monofunctional alkylating agents, EI, EMS and ICR-177. It is suggested, therefore, that the mechanism of mutation induction by metronidazole in Neurospora is similar to that of monofunctional alkylating agents.


Reactions of 3-ethoxy-2-oxobutyraldehyde bis(N4-dimethylthiosemicarbazonato) cadmium with tumor cells. The cytotoxic properties of a bis(thiosemicarbazonato) cadmium complex are studied. Preincubation of Ehrlich cells with the complex prevents growth of the ascites tumor in mice. Although the complex inhibits tumor growth without undue initial toxocity, longer-term side effects limit the use of the compound. The complex inhibits incorporation of 3H-thymidine into DNA and the respiration of tumor cells. It is shown in the principal correlation that the complex is more inhibitory of the above biochemical processes than cadmium ion at equal cellular concentrations of the metal. In addition the cellular reactions of the cadmium, zinc, and copper bis(thiosemicarbazonato) complexes are compared. It is shown that subtle chemical differences in their chelate structures appear to be responsible for their marked differences in cellular reactivity.


Pathogenesis of ano-rectal incontinence. A histometric study of the anal sphincter musculature. Type 1 fibre predominance was found in the external anal sphincter, puborectalis and levator ani muscles of 17 control subjects, and of 16 patients with ano-rectal incontinence. In the external anal sphincter and puborectalis muscles of the control subjects the mean diameter of Type 2 fibres was slightly greater than that of Type 1 fibres, but in the levator ani muscles of control female subjects the mean diameter of Type 1 fibres was much greater than that of Type 2 fibres. In the patients with anorectal incontinence there was marked hypertrophy of fibres of both histochemical types. This was most marked in the puborectalis and external anal sphincter muscles. In 12 of the 16 incontinent patients there were histological and statistical features consistent with a neurogenic disorder. These histometric studies provide a quantitative basis for physiological and pathological studies of these muscles in incontinence and other anorectal disorders.


Familial carnitine deficiency. A fatal case and subclinical state in a sister. A 15-year-old girl with a large accumulation of lipid in the muscle fibers, was suffering from systemic carnitine deficiency. She died in acidosis. The blood carnitine level was normal. At necropsy, carnitine levels were low in skeletal muscles and heart, whilst a normal level was found in the liver. Carnitine palmitoyltransferase II and palmitoyl-CoA synthetase activities were increased, whereas carnitine acetyltransferase, glycerol-3-phosphate dehydrogenase (FAD) and succinate dehydrogenase were decreased. Investigation of blood and skeletal muscle of the family members revealed marked abnormalities in a 7-year old sister who had only minor neurological symptoms. Histochemical investigation revealed abnormal accumulations of lipid between the myofibrils. Carnitine was decreased in her skeletal muscle and blood. Muscular carnitine palmitoyltransferase II and palmitoyl-CoA synthetase were again increased in activity while glycerol-3-phosphate dehydrogenase (FAD) was decreased. The activities of succinate dehydrogenase, carnitine palmitoyltransferase I and glycerol-3-phosphate dehydrogenase (NAD+) were normal. The unexpected normal carnitine level in blood and liver of the deceased patient was attributed to muscle wasting, which was confirmed by the very high blood level of creatine phosphokinase. This fatal case indicates that the fasting condition must be avoided in persons with carnitine deficiency. In crises, glucose supply is necessary since gluconeogenesis may be blocked.


The anatomy of the so-called "articular nerves" and their relationship to facet denervation in the treatment of low-back pain. Disections of the dorsal rami of L1--5 were performed in human cadavers, and the course of the dorsal rami, their branches, and the innervation of the zygapophyseal joints in the lumbar region were specifically studied. At the L-1 through L-4 levels, the dorsal rami divide into medial and lateral branches within the intertransverse ligaments. Each medial branch runs across the root of the adjacent superior articular process. At the caudal edge of the process, the branch turns medially beneath the mammillo-accessory ligament. Beneath the mammillo-accessory ligament, medial branches occur that innervate the adjacent zygapophyseal joint, and distal zygapophyseal branches arise at the laminar level to innervate the next lower joint. The L-5 dorsal ramus runs along a groove between the ala of the sacrum and its superior articular process. A the caudal edge of the articular process, the ramus divides into medial and lateral branches, and the medial branch supplies the L5--S1 articulation.


Susceptibility of kappa-casein components to various proteases. In order to clarify the function of the carbohydrate moiety of bovine kappa-casein, kappa-casein components having different carbohydrate contents were prepared by DEAE-cellulose chromatography. Five adsorbed fractions so obtained had an identical peptide chain and contained carbohydrate moieties of increasing size in the order of components P-2, P-3, P-4, P-5 and P-6. The subsceptibility of kappa-casein components, having different carbohydrate contents, to various proteases was examined. kappa-Casein components were subjected to calf rennin  [chymosin; EC 3.4.23.4], bovine trypsin [EC 3.4.21.4], alpha-chymotrypsin [EC 3.4.21.1], pronase [EC 3.4.24.4] and human plasmin [EC 3.4.21.7]. The component containing a larger carbohydrate moiety was less susceptible to hydrolysis than the component containing a smaller carbohydrate moiety. Rennin, trypsin, alpha-chymotrypsin and pronase hydrolyzed each component with a different reaction rate. On the contrary, human plasmin hydrolyzed component P-2, but did not hydrolyze component P-5. These results indicate that the carbohydrate moiety of kappa-casein components to various proteases.


Gastroesophageal reflux among severely retarded children. Of 136 institutionalized severely retarded children, 20 (15%) had recurrent vomiting. Of these 20, 15 had gastroesophageal reflux diagnosed by x-ray examination, acid reflux text, or both. Esophagitis was noted by endoscopy in ten of 14 patients with GER. Four patients were anemic and six had had one or more episodes of aspiration pneumonia in the 12 months prior to study. Reduced basal lower esophageal sphincter pressure was the most common manometric abnormality noted in the patients with GER. Responses of the LES to bethanechol and swallow were normal, as was the basal pressure of the upper esophageal sphincter. Abnormal propagation of esophageal peristalsis was seen in six patients, all of whom had moderate or severe esophagitis. When compared to the nonvomiting retarded patients, the GER patients had significantly lower mental age and higher incidence of scoliosis. Patients with GER who had basal LES pressure less than 10 mm Hg did not improve with medical management. Recurrent vomiting is a common and serious problem in severely retarded children, the organic cause of which can be demonstrated by the application of appropriate investigative techniques.


Urethral obstruction malformation complex: a cause of abdominal muscle deficiency and the "prune belly". Abdominal muscle deficiency with a "prune belly" abdomen as been a major feature of the so-called prune belly syndrome, which has been regarded as a specific entity, although the etiology and developmental pathology are not understood. We present evidence that abdominal muscle deficiency is an etiologically nonspecific anatomic defect which is secondary to fetal abdominal distention of various causes. One of the more common causes is urethral obstruction with consequent early bladder distention, causing abdominal distention and other anomalies, a constellation of findings which we have termed the urethral obstruction malformation complex. This interpretation of the etiology of most cases of prune belly syndrome accounts for the male predominance, the observed variability in severity, and the lack of a defined mode of inheritance. Recurrence risk figures need to be redefined for each specific obstructing lesion of the urethra. The possibility of early prenatal diagnosis and management of fetuses with urethral obstruction needs further study.


Fine structure of a racemose cysticercus from human brain. The surface of a racemose cysticercus from the human brain was studied by scanning electron microscopy and the tegument of the cyst by transmission electron microscopy. The surface of the larva is covered by microvilli of uniform shape and size. The glycocalyx of the microvilli bears knotlike areas positive for acid mucopolysaccharides. Microvilli are interconnected by a fine, electron-dense network. The tegumental and subtegumental tissues vary in thickness from one region to the next, and the tissues below the vesicular layer are scattered irregularly, in a seemingly disordered manner.


Surgical experience with expanded polytetrafluoroethylene (PTFE) as a replacement graft for traumatized vessels. With the increased nationwide incidence of major vascular injuries, the need for interposition grafting has become quite common in major trauma centers. Despite extensive experience with such injuries, the choice of a substitute conduit remains controversial. Recent studies have demonstrated the potential of expanded polytetrafluoroethylene (PTFE) as a replacement graft for small arteries and veins. The surgical services at the Ben Taub General Hospital began to use PTFE grafts in traumatic vascular wounds approximately 2 years ago. Eight axillary arteries and 12 brachial arteries have had interposition grafting with PTFE prostheses. Eleven patients have required PTFE interposition grafts in repair of traumatized common, superficial, and profunda femoris arteries and common femoral veins; eight patients had reconstruction in the popliteal artery or vein. Three patients had renal artery revascularization procedures following blunt abdominal trauma, three patient had segmental replacement of the superior mesenteric artery following gunshot wounds, and one carotid artery, one iliac vein, and two axillary veins were grafted with PTFE. All patients with segmental repair of axillary, brachial, femoral, and popliteal vessels have maintained good distal pulses and viable extremities. No grafts have thrombosed, nor become infected, in spite of soft-tissue injury encountered at time or repair. In situations requiring interposition graft placement for reestablishment of distal flow in small arteries and veins, PTFE grafts appear to be an acceptable prosthesis.


Quantitative analysis of dermatoglyphics. (2) Dermatoglyphic patterns. Using medical students as controls, we devised a method of quantitative analysis of dermatoglyphic patterns. We calculated the frequency of appearance of each of the patterns and obtained the probability of occurrence of the dermatoglyphics of each of the controls. We showed usefulness of this method by presenting some examples of congenital anomalies where this has been put to use. Furthermore, patients with congential heart disease were compared with controls by this method.


Exercise stress myocardial perfusion scintigraphy with thallium-201. We performed exercise stress scintigraphy with thallium-201 in 88 patients including 31 patients of effort angina and nine patients of old myocardial infarction without angina. Sensitivity of exercise stress scintigraphy to detect effort angina was 77%, whereas sensitivity of exercise stress ECG was only 44.5%. The combination of stress scintigraphy with stress ECG enhanced sensitivity up to 87%. Exercise stress scintigraphy was useful particularly in cases with one vessel disease and those who failed to achieve sufficient exercise stress. Besides exercise stress scintigraphy did not show false positive response, differing from exercise stress ECG. Myocardial imaging is a method which shows the balance between myocardial perfusion demand and supply.


Importance of heart weight, weights of cardiac ventricles and left ventricle plus septum/right ventricle ratio in assessing cardiac hypertrophy. The present communication deals with the observations made during the study of 140 hearts (138 from medico-legal postmortems and 2 from post-natal deaths). The formalin fixed heart was dissected to separate non-muscular portion (NMP), right ventricle (RV), and left ventricle with septum (LV + S). The weights of the different components of the adult heart were affected by sex and body built not by age or body length. In most of the hearts the total weight varied from 180 to 320 Gm, the weight of RV, from 40 to 80 Gm, and LV + S, from 100 to 180 Gm. NMP was neither affected by age nor by ventricular weight. The coefficient of correlation between the heart weight and NMP was 0.93. Heart weight in Gm could be represented as equaled to 38.89 + 4.09 NMP. LV + S/RV ratio ranged from 1.64-3.84 : 1 in males and 1.73--3.1 : 1 in females, averaged being 2.52 : 1 and 2.44 : 1 respectively. No correlation between the weights of RV and LV + S was found. An attempt has been made to lay down the criterion for normal heart and for ventricular hypertrophy. The importance of total heart weight, weights of ventricles and the ratio is assessment of cardiac hypertrophy is discussed.


The estimation of heart weight from routine chest X-ray films. A formula to estimate heart weight was derived using a theory of quantification which employed the measurements of cardiac silhouette taken from routine postero-anterior projection chest X-ray film. The films obtained in 73 necropsied cases of essential hypertension, renal hypertension, mitral and aortic valvular diseases, and 62 necropsied cases with other diseases were used for derivation of the formula. The measurements of the horizontal distances from the midsternal line to the intersecting point of the lower margin of each rib along the left cardiac border, and of the greatest distance along the right cardiac border were employed; body height, age and sex were also included. The heart weight estimated by this formula coincided with the heart weight measured at necropsy with a high correlation coefficient of 0.81. The correlation rate in 34 external samples was also significantly high, being 0.72. These results indicate the practical usefulness of this formula.


Homologous and heterologous connective tissue tube for vascular substitute. A newly-developed vascular graft having many advantages over the fabric vascular prosthesis was evaluated as aortic and vena caval substitutes. Alcohol-preserved connective tissue tubes, obtained from dogs and calves, supported by polyester mesh were implanted into the thoracic aortae of 61 dogs and the superior vena cava of 24 dogs. In the case of the aortic experiment, all the tested animals were healthy and each graft was patent at the time of removal. In the case of the vena caval experiment, all the tested animals were healthy, but 10 of 24 grafts were occluded. Aneurysmal dilatation, immune response and regressive changes of newly formed neointima were not observed in any case. Moreover, no blood leakage through the graft wall was observed. Leakage at the line of anastomosis was very little. The great advantage of the graft was good endothelization of the neointima. Between the grafts obtained from dogs and calves, there was no difference in the process of their healing.


Human B-cell antigens in acute lymphocytic leukemia. Lack of correlation with other lymphocyte surface markers. Cells from patients with acute lymphocytic leukemia were studied for cell surface markers and B-cel alloantigens. Three cell types were defined. Those spontaneously rosetting with erythrocytes and not prossessing surface immunoglobulin or complement receptors were considered T-cells. Cells not showing rosette formation, surface immunoglobulin, or complement receptors were considered null cells and could be divided into two categories based on their ability to stimulate in mixed lymphocyte reaction. B-cell alloantigens were found randomly distributed on all cell types. The results suggested that genetic information for human B-cell antigens was present in all cell types and that other cell surface markers may reflect a stage of differentiation of the leukemia cell type.


Suppressor cells in the pelvic lymph nodes regional to bladder cancer. Regional lymph node cells from some patients with locally advanced bladder carcinoma were found to inhibit the reactivity of normal and autologous peripheral blood lymphocytes in mixed leukocyte culture. The data suggest that suppressor cells are generated in draining lymph nodes of these patients by a high concentration of tumor-derived products and may have suppressive influence on host immunologic defense mechanisms.


Pulmonary artery banding in infants with complete atrioventricular canal. Management of symptomatic atrioventricular canal (AVC) in infancy may be difficult. Between July, 1969, and September, 1977, 31 infants with complete AVC presented in congestive heart failure (CHF) to the University of Minnesota Hospitals. Fifteen of these patients have responded to medical management and have been followed as outpatients. The other 16 patients remained in CHF. Six of them died of persistent heart failure within 4 months. The other 10 infants, aged 3 weeks to 1 year (mean 4 months), underwent pulmonary artery banding and seven survived operation. One of the survivors died with apparent pneumonia 1 month postoperatively. Each of the remaining six patients, who have been followed for 9 months to 9 years, had minimal mitral insufficiency and a large ventricular shunt. The three patients dying after banding had significant mitral insufficiency. We believe that pulmonary artery banding is an effective palliative procedure for infants with complete AVC and CHF who have large ventricular shunts and minimal mitral insufficiency.


New approach to protein-losing gastroenteropathy. Fibrinolytic activity in the biopsied gastrointestinal mucosa was investigated in patients with protein-losing gastroenteropathy, and the increased activity was observed in patients associated with erosive gastritis, Menetrier's disease, atrophic gastritis, or Crohn's disease. However, patients with intestinal lymphangiectasia showed normal mucosal fibrinolysis. Antifibrinolytic therapy with tranexamic acid revealed significant therapeutic effect in the group with increased mucosal fibrinolysis. It is concluded that tranexamic acid appeared to be successful in blocking the vicious circle of "membrane disorder","increased tissue fibrinolysis", "increased vascular permeability", and "hypoproteinemia" in protein-losing gastroenteropathy.


Exteroceptive, proprioceptive, and sympathetic activity recorded with microelectrodes from human peripheral nerves. With tungsten microelectrodes percutaneously inserted into human peripheral nerve fascicles, in vivo recordings of single-unit action potentials can be obtained from different types of myelinated and unmyelinated nerve fibers. This technique of microneurography has provided a great deal of information about (1) the sensory innervation of the human skin, with its mechanoreceptive, thermoreceptive, and nociceptive functions, (2) the proprioceptive innervation of human skeletal muscles, special attention being devoted to the motor control functions of the muscle spindles and the fusimotor system, and (3) the sympathetic innervation of autonomic effector organs in skin and muscle, with its significance for, for example, regulation of temperature and blood pressure. The technique has its main application not as a routine procedure in clinical diagnostic work but as a research tool in basic physiologic and pathophysiologic studies.


HLA.

HLA. HLA typing in 1979 is more complex and more complete than in former years. The distribution of antigens in the HLA system and various methods of identifying them and of determining their structure and function are described. The usefulness of HLA typing in organ transplantation and paternity testing has been well established, and its place in blood component therapy is to some degree still conjectural. Detection of HLA antigens associated either positively or negatively with specific disease states has great importance for several reasons. From an academic point of view, these association may help to define pathogenetic mechanisms, and from a practical viewpoint, there is now good reason to believe that HLA typing may shortly be useful as a diagnostic and predictive tool. Further elucidation of the role of the HLA molecules in the immune response gives hope for better understanding of the immune and autoimmune disorders, which is surely the first step in defining rationally based therapeutic regimens.


Otitis media and the immotile cilia syndrome. The immotile cilia syndrome appears to be a congenital defect in the ultrastructure of cilia that renders them incapable of movement. Respiratory tract cilia and sperm are predominantly affected. Bronchiectasis, sinusitis and male sterility are the main clinical findings. Situs inversus may be found. To these findings can be added otitis media. The defect appears to be a complete or partial absence of dynein arms which are believed to be essential for generating movement of cilia or sperm tails. Six patients suspected of having immotile cilia were compared to six patients in a control group. In affected patients, no cilia movement in the middle ear or nasopharynx was observed using the operating microscope. Electron microscopy of cilia from the mucosa of the middle ear and nasopharynx appeared to confirm the ultrastructural defect in two of six patients suspected of having the syndrome.


Metabolism of lipids in experimental hypertrophic hearts of rabbits. Cardiac hypertrophy was induced in rabbits by subcutaneous injection of thyroxine or isoprenaline or by surgically constricting the abdominal aorta. Alterations in lipid metabolism were observed in these hypertrophic hearts. Thyroxine or isoprenaline treatment increased the fatty acids in the serum and stimulated a marked increase in total lipids, triglycerides, and fatty acids in the hypertrophied myocardium. Coarctation of the aorta, in contrast, induced a significant increase in these lipids without significantly affecting serum free fatty acids. Histochemical and morphological studies confirmed an increase in neutral lipids. It is suggested that the observed increase in fatty acids in the heart following thyroxine or isoprenaline treatment is related to the increase in serum free fatty acids, which is followed by an increase in the removal of serum fatty acids by the heart. However, the amount of serum fatty acids that is removed exceeds the amount that is oxidized, which leads to an increase in lipid stores. The increase in lipid stores in the heart following coarctation of the aorta probably corresponds to the decrease in myocardial concentrations of carnitine. Serum lipid levels following coarctation were not significantly different from those of controls.


Constitutive expression in Escherichia coli of the Neurospora crassa structural gene encoding the inducible enzyme catabolic dehydroquinase. In Neurospora crassa the qa-2 gene, which encodes catabolic dehydroquinase, is under positive control exerted by the inducer quinic acid and an activator protein encoded in the closely linked qa-1 gene. In order to determine if this regulatory mechanism is maintained when the qa-2 gene is cloned on a recombinant plasmid and expressed in Escherichia coli, molecular cloning experiments have been performed using DNA isolated from a qa-1+ (inducible), a qa-1C (constitutive) and two qa-1 (non-inducible) strains of N. crassa. The results demonstrate that the level of expression of the qa-2 gene in E. coli is completely independent of the mutational state of the qa-1 gene. Moreover, the level of expression of the cloned qa-2 gene was unaffected by either an intracellularly produced inducer of catabolic dehydroquinase or by the general procaryotic positive effector, the CAP factor. The weight of evidence thus supports the conclusion that transcription of the N. crassa qa-2 gene in E. coli does not require the qa-1 activator protein and thus is not controlled by the same mecahnism which functions in N. crassa.


"Prune Belly" syndrome.

"Prune Belly" syndrome. A large sonolucent mass was first revealed by the ultrasonic echography examination of a fetus at 18 1/2 weeks' gestation, but was no longer present at 28 1/2 weeks' gestation. The fetus was subsequently born with the "prune belly" syndrome. The case is described, and the possible causes, and possibilities of prevention, of "prune belly" are discussed.


Structure and control of phosphofructokinase from Bacillus stearothermophilus. The allosteric enzyme phosphofructokinase binds its substrate fructose-6-phosphate between two subunits of the tetramer, and allosteric effectors between another pair of subunits. The effector binding site accommodates both the activator and the inhibitor. The substrate cooperativity and allosteric control are mediated by these ligand bridges between subunits.


Development and mechanism of barbiturate tolerance in glial cell cultures. The effects of exposure of glial cells in primary culture and in continuous line (clone NN) to pentobarbital over various periods of time on cellular respiration and activities of enzymes involved in carbohydrate metabolism were studied. The results obtained in glial cells in primary culture were qualitatively identical to those obtained in glial cells in clonal line (NN). Both types of glial cells were shown to develop biochemical tolerance to pentobarbital as defined by an attenuated response to the depressant effects of a challenging dose of pentobarbital on cellular respiration in barbiturate-cultivated cells compared to those grown in drug-free medium. The biochemical tolerance was evident in the presence of glucose and succinate but not malate as substrate. This tolerance to pentobarbital was accompanied by increased activities of hexokinase, glucose-6-phosphate dehydrogenase, succinate dehydrogenase, and glutamate dehydrogenase and by a marked increase in the number of glial cell mitochondria as observed in electron micrographs. The results are interpreted to indicate a compensation of glial cells to the continuous presence of PB by an accelerated glucose uptake and metabolism, an accelerated metabolism of succinate, and an increased mitochondrial activity.


Isoniazid therapy of Huntington disease. We describe clinical and biochemical changes in seven patients with Huntington disease given isoniazid (INH) in dosages three to five greater than normally used in tuberculosis. Because INH inhibits the enzyme gamma-aminobutyric acid aminotransferase (GABA-T), and increases GABA content in the brains of experimental animals, it might correct the brain GABA deficiency characteristic of Huntington disease. Of six patients treated long enough to be clinically evaluated, one showed marked and two others showed signifciant improvement. High-dose INH therapy carries serious toxic risks, which are influenced by patients' acetylator phenotypes. Nevertheless, results are sufficiently promising to warrant further controlled trials of INH or other GABA-T inhibitors in Huntington disease.


[Histoenzymatic changes and dosimetric studies of some organs and areas, using diagnostic radioisotopes. Critical review of a 10-year experiment]. Ten years experience of dosimetry and study of the histochemical changes brought on by internal irradiation are reviewed. The research is broken down into three stages: 1) identification of enzymatic damage in small laboratory animals; 2) study of the dose really absorbed at various points of critical organs of large animals, 3) the collection of histoenzymatic data resulting from research on large animals treated internally with isotopes commonly used in diagnosis.


The passive hamstring stretch test: clinical evaluation. The passive hamstring stretch test is described. Using a modified goniometer it is shown that independent measurements taken by trained examiners approximate very closely to each other. This establishes the test as a valid objective measurement. The possible value of this test as a research tool in low back pain problems is discussed.


Silicone band sterilization with radiographic and laparoscopic evaluation. Laparoscopic tubal sterilization, using a Silastic band to occlude the tubal lumen, was performed on 224 patients. The incidence of complications was low and only 2 pregnancies occurred. Further evaluation by hysterosalpingography on 97 patients revealed 2 distinct images. The site of tubal occlusion was seen on laparoscopy performed on 7 patients. The radiographic and laparoscopic findings are discussed.