The vascular basis of the positional influence of the intraocular pressure. By measuring intraocular pressure in different body positions from 60 degrees semiupright to 30 degrees head down, a nonlinear relationship between IOP increase and body position was confirmed. IOP postural response in individual subjects was roughly correlated to ophthalmic arterial pressure and to the episcleral venous pressure postural response. In one series of subjects, the episcleral venous pressure increments due to posture wa; parallel to the applanation-indentation disparity in the same individual eyes. Differential tonometry with applanation or indentation procedures under blind conditions gave significantly low indentation readings. It is concluded that IOP postural response depends on arterial and venous vascular changes when subjects move from an erect to a horizontal body position. Blood expulsion from the choroid by indentation tonometry might be the reason that this tonometric procedure does not measure IOP changes based on vascular changes.


[Changes in the content in reduced and oxydized glutathione in incubated bovine lenses (author's transl)]. Incubation of bovine lenses over a period of 24 h in Krebs-Ringer solution effects a decrease in the content of GSH. This decrease can be blocked by addition of 2 mM/1, each of glycine, glutamic acid, and cysteine. The content in GSSG is in no way influenced by incubation with or without addition of the three amino acids.


In vitro release of fibrinolytic activators from cornea. Rabbit corneas cultured in vitro in chemically defined media continuously released fibrinolytic agents. Such a substance was an activator of plasminogen and was released largely from the epithelium. Addition of prednisolone did not modify fibrinolytic activity, while death of the explants was followed by cessation of fibrinolysis, a finding suggesting synthesis of the activator during culture.


The distribution and some properties of collagenolytic cathepsin in the bovine eye. In vitro degradation of insoluble vitreous collagen by the action of collagenolytic cathepsin was studied biochemically. Among bovine ocular tissues, the uvea and the retina showed relatively high collagenolytic activity. The ciliary body revealed the highest specific activities of both cathepsin B and collagenolytic cathepsin. Leupeptin and p-chloromercuribenzoate inhibited both cathepsin B and collagenolytic cathepsin in the ciliary body lysosomes. Pepstatin inhibited cathepsin D, but did not affect cathepsin B and collagenolytic cathepsin. It is suggested that distribution and properties of collagenolytic cathepsin are similar to those of cathepsin B in the bovine eye.


Central serous choroidopathy with bullous retinal detachment. We report here a new type of secondary retinal detachment that has never been clearly defined. The characteristic features of the disease are: (1) prevalence in middle-aged males, (2) bilateral involvement, (3) frequent existence of prodromal lesions that over long periods resemble central serous retinopathy, (4) in the evolution stage, appearance of multiple yellowish white exudative flecks of one-half to one disc in diameter at or near the posterior pole of the fundus, (5) fluorescein studies revealing pronounced leakage of dye from the choroid into the subretinal space at the sites of exudates, (6) retinal detachment of various degrees with shifting subretinal fluid and without tears, (7) no evidence of intraocular inflammation, (8) no filling abnormalities seen in the choroidal fluorescence, (9) no response to medical therapy, including steroids and antibiotics, (10) photocoagulation to leakage sites leading to rapid resolution of retinal detachment; otherwise, spontaneous healing of detachment occurring within about 7-9 months, leaving fibroblastic macular scars and marked visual loss, and (11) no evidence of systemic findings that may be of etiologic significance. From this characteristic clinical picture, the idea of a new clinical entity must be considered. Our findings in 35 eyes from 18 Japanese patients are discussed.


[Enzyme activities of bovine aqueous humour in dependence on age (author's transl)]. The specific activities of LDH, MDH and ALD of bovine aqueous humour show no significant changes in dependence on age. The protein content remains constant too. Determination of the enzyme activities of Sorbitoldehydrogenase and Pyruvatekinase was not successful due to disturbing activities of the crude aqueous. Substrate affinities (KM-value) of LDH, MDH and ALD are almost identical in aqueous, serum and lens of the bovine.


[The tensile strength of human zonule and its alteration with age (author's transl)]. A series of 91 cryoextractions was performed on autopsy material. The scleral section was placed near to the chamber angle and was nearly circumferential (about 330 degrees). Cornea and adjacent sclera could be flapped over this way, and did not interfere with a straightforward lens extraction. The pupil was medically dilated. A cryoprobe was fixed to a specially constructed scale, and frozen to the anterior pole of the lens. Its weight was counterbalanced by a plastic water container at the other end of the scale. The extraction was performed by filling additional water into the counterbalancing container. The statistical evaluation of the results showed a very significant dependence of the average tensile strength on age. However, a considerable standard deviation was found throughout all ages. The nutritional state of the autopsy bodies and the time interval between death and start of the measurement had no significant influence. The differences between right and left eyes were also not significant, as could be expected. The methodological error remained small. Age proved to be an unreliable indicator for the tensile strength of the zonule. All results apply to clear lenses. We known from clinical experience that the tenacity of the zonule may also be different in the various types of cataract.


Primary mediastinal choriocarcinoma in a male metastatic to the choroid. A rare metastatic choroidal tumor from primary mediastinal choriocarcinoma in a male is described. This tumor secreted gonadotrophins and showed the histopathologic characteristics of cytotrophoblast and syncytiotrophoblast cells. Early metastatic disease resulted in rapid death; the development of the choroidal metastatic lesion was diagnosed at autopsy.


An injection/circulation-timing switch for angiography. An injection/circulation-timing switch was developed to simply and precisely initiate the timing unit of the fundus camera for angiographic documentation. After starting the timer, the switch, mounted on the syringe used for injection of the tracer material, subsequently provides documentation of the total elapsed time of injection. Such quantitative data can enhance the evaluation of angiographic results and contribute to their universal comparability when combined with such qualitative data as injection location and total injectate.


[Light- and electron-microscopic examinations of deep keratomycosis (aspergillosis) (author's transl)]. Light-microscopic and ultrastructural examinations of a corneal button with deep keratomycosis revealed that keratocytes are partly injured and partly of normal structure. In the cellular reaction, macrophages especially, are found that encircle hyphae with pseudopodia or cover the apical end of the fungi. In many sections, the fungal walls are very resistant to phygocytosis, but, on the contrary, the cytoplasm is damaged earlier and more severely. The cellular reaction in the anterior chamber is massive and intensive with predominance of macrophages.


Bilateral internal mammary artery mobilization and sternal healing. Four instances of mediastinal wound infection occurred in 100 patients who underwent bilateral internal mammary artery (IMA) mobilization for coronary bypass. Debridement of 3--5 mm of the sternal edges was performed 6--18 days after the primary operation, and 2 patients required additional, anatomically limited debridement. Wounds were allowed to heal by secondary intention. The wounds of 3 patients healed by 4, 7, and 16 months; they had patent grafts at the postoperative or 1-year catheterization; and they returned to work and are free of angina. The fourth patient died of renal and respiratory failure 3 months after the operation; his wound was healing and had not required additional debridement. These observations indicate that bilateral IMA mobilization does not result in avascularity of the sternum, which required only limited debridement and quickly formed granulation tissue from the periosteum and marrow.


The noninvasive diagnosis of thrombophlebitis in the lower extremities: clinical value of plethysmography combined with augmentation methods and a new scoring system. Venous impedance plethysmography and respiratory-compression Doppler augmentation responses have proved to be diagnostically valuable in suspected thrombophlebitis of the lower extremities. These noninvasive methods can provide quantitative and reproducible data on the basis of which the presence of  increased deep venous resistance can be confirmed, suspected, or doubted. A new scoring system for the composite evaluation of data from 100 consecutive  patients with possible thrombophlebitis, pulmonary embolism, or both, is presented. These procedures assume added importance in view of the diagnostic limitations, and even potential hazards, of other methods. These methods indluce lung scanning, radioactive fibrinogen scanning, venography, and pulmonary angiography. Serial studies can be performed with impunity for following highrisk patients and evaluating various therapeutic or prophylactic measures. The importance of monitoring the femoral-popliteal segment is emphasized, because of the greater propensity for massive pulmonary thromboembolism from thrombi in these veins than in the calf vessels. Clinical observations coupled with these studies underscore the fallacy of several widely-held diagnostic biases pertaining to deep venous thrombosis and pulmonary thromboembolism. The long-term followup of 12 patients in whom inferior vena cava unbrellas has been inserted for life-threatening pulmonary embolism is presented. The possible propensity to deep vein thrombosis from vitamin E therapy is raised.


The effects of corticosteroid administration on the bronchoalveolar cells obtained from guinea pigs by lung lavage. The effects of systemic administration of corticosteroids on the bronchoalveolar cell population obtained from guinea pigs by lung lavage were studied. The results of this study demonstrate that in contrast to the marked decrease in the percentage of T lymphocytes in the peripheral blood of animals treated with steroids, there was no significant decrease in the percentage of T lymphocytes in the bronchoalveolar cell population. In addition, corticosteroid administration did not significantly affect either the number of alveolar macrophages obtained by lavage or the Fc receptor activity of these cells. When considered in the context of previously reported data, these results emphasize that caution must be used in reaching conclusions about the integrity of the pulmonary immune response from the results of studies using a bronchoalveolar cell population obtained by lung lavage. This observation must be considered when evaluating the significance of studies of the human pulmonary immune response performed with cells obtained by segmental bronchopulmonary lavage.


The incidence of colour-blindness among the tribal populations of Andhra Pradesh. Among 126 Valmiki, 128 Bagatha, 129 Konda Dora and 73 Samanta tribals of Andhra Pradesh, the incidence of red-green colour-blindness in the males ranges from zero to 2.27 per cent. Samanta males exhibit no colour-blindness. In the females, only Konda Doras exhibit a frequency of 2.44 per cent of the trait. Comparison of the present data with the other available tribal and non-tribal data of Andhra Pradesh shows that our results fall well in the range for other data. Post's (1962) hypothesis of relaxation of selection against colour-blindness is also supported by our Andhra Pradesh data.


The effects of single-dose alternate-day prednisone therapy on the immunological status of patients with neuromuscular diseases. Several immunological variables were examined in patients receiving high-single-dose, alternate-day prednisone therapy for neuromuscular diseases. Dose-dependent leukocytosis, lymphopenia, and monocytopenia occurred which were maximal 6 hours after prednisone administration but returned to control levels by the 24-hour point. The lymphopenia involved T-cells, B-cells, and null cells, with the T-cells most affected. Plasma cortisol levels and lymphocyte transformation in response to mitogens were also transiently and reversibly suppressed. There was a persistent decrease in serum IgG. Lymphocyte transformation was also suppressed when normal lymphocytes were incubated with treated patient sera or when treated patient lymphocytes were incubated in autologous pretreatment sera. The suppression factor was not removed from the lymphocytes by extensive washing. Patients whose disease responded to the high-single-dose, alternate-day prednisone regiment were indistinguishable from nonresponders by the immunological responses measured.


Crista neglecta in man.

Crista neglecta in man. The prevalence, location, and size of the crista neglecta in man were investigated by examining the histological sections of 223 human temporal bones (137 cases). The relationship between the crista neglecta and the singular nerve was also described. The crista neglecta was observed in 17 cases, ranging in age from 15-week fetal life to 76 years. This structure was located on the wall of the anterolateral quadrant of the posterior canal ampulla, close to the cribriform area of the singular nerve in the area between the utriculoampullar duct and the intermediate portion of the posterior canal crista. The average width, length, and height of the crista neglecta were described. The crista neglecta had a mound-like shape and contained nerve fibers, transitional epithelium, sensory hair cells, and a cupula. The nerve fibers from the crista neglecta were joined to a small branch of the singular nerve at the cribriform area in 5 of 17 crista neglecta cases, and to the main trunk of the singular nerve in the remaining 12 cases.


Significance of surface immunoglobulin in murine and human myeloma and chronic lymphocytic leukemia. One important factor in the production of the immunologic deficiency in myeloma appears to be the alteration of the surface immunoglobulin by a macromolecular, RNA containing factor released by the tumor. In contrast, the cells of chronic lymphocytic leukemia are not influenced by factors outside the cell and their lack of immunologic reactivity is due to an intrinsic defect. These characteristics may be occasionally important in differential-diagnostic considerations.


Intraoperative posterior left ventricular wall rupture associated with mitral valve replacement. An unusual but often lethal complication of mitral valve replacement is rupture of the left ventricle. The two recognized types of rupture are discussed, and the literature and pathology are reviewed. It is stressed that this complication can be prevented, and the factors involved in prevention are outlined.


The de facto US mental health services system: a public health perspective. The President's Commission on Mental Health has highlighted a heretofore unmet need for the linkage of data on the prevalence of mental disorder with national data on the use of mental health services. This study analyzes available epidemiological data and recent mental health services research findings to estimate the percent of the population with a mental disorder and the proportion utilizing various types of specialty mental health and general medical treatment settings. Provisional estimates indicate that at least 15% of the US population is affected by mental disorders in one year. In 1975, only one fifth of these were served in the specialty mental health sector, with about three fifths identified in the general medical (primary care) sector.


Prevalence of depression over a 12-month period in a nonpatient population. A nonpatient population of air traffic controllers, all of whom remained employed during the observation period, was examined monthly for one year for level of depression using the Zung Self-Rating Depression Scale. The average monthly prevalence of depression was 9.1%, with 7.0% at the symptom level, 1.9% at a level comparable to outpatients, and 0.2% with moderately severe levels. These figures were generally similar to those for other reported population groups, although exact comparisons were difficult because of the preselection for health in this population. Two patterns of depression were observed. One was characterized by an acute, episodic symptomatology returning to nonsymptomatic levels for most of the year, similar to Research Diagnostic Criteria (RDC) category "episodic minor depressive disorder." The other showed a chronic, fluctuating course with significant depressive symptomatology over half the year, similar to RDC category "chronic and intermittent minor depressive disorder."


Colony-stimulating activity.

Colony-stimulating activity. Hemopoietic cells, when placed in single-cell suspension in a semisolid growth medium for seven to 14 days, have been found to form visible colonies of granulocytes and monocytes. Colony growth appears only in cultures to which a source of colony-stimulating activity (CSA) is added. Because of these in vitro effects, CSA is thought to be an in vivo regulator of granulocyte and monocyte production from progenitor cells in the bone marrow.


Pathology of coronary artery bypass graft surgery. Coronary artery bypass graft surgery has been available and widely successful for the symptomatic treatment of ischemic heart disease. Despite its widespread use, there is little information available on the pathological consequences of this procedure on the human heart. In this article, morphological consequences of coronary artery bypass graft surgery is reviewed. Intimal changes occurring within the vein graft itself consist predominately of fibrous initimal proliferation, which in some patients may progress to from an occlusive plaque. Most occlusions, however, occur at the coronary artery bypass graft anastomosis site and the mechanisms of occlusion include compression of the vascular lumen, thrombosis, and dissection of the coronary artery. Most graft failure occurs in the setting of too small a native coronary artery lumen. The myocardium is also at risk for alterations as a result of the bypass operation. Contraction band or reperfusion necrosis is the type of injury most commonly seen, and it appears to occur most often in the distribution of patent grafts. Accelerated atherosclerosis in vein grafts and the myocardial injury associated with revascularization require further detailed morphological studies, but these are important areas for pathological exploration since they bear on important and yet unanswered questions about coronary bypass surgery: can it in the long run perserve myocardium and prolong life?


Atherosclerotic aneurysm in aortocoronary vein graft. An atherosclerotic aneurysm was found in aortocoronary vein grafts of two patients who had a second revascularization because of reappearance of anginal symptoms five and six years, respectively, after the initial bypass operation.


[Condensor field irradiation (27.12 mhz) and osteosynthetic implants (author's transl)]. The question whether metals implanted in tissue may induce heat damage is yet controversial. Due to physical laws an increased production of heat is to be expected around the metal parts directed towards the capacitor plates. This is due to a converging and shunting effect of the metal in the electric field. Model experiments show that the shunting effect is most significance for the production of heat damage close to the metal. No heat damage is to be expected under the four following conditions: 1. linear or 2-dimensional osteosynthesis implantats are in a rectangular position to the electric field, 2. the metal is covered with at least 10 mm of tissue, 3. the tissue between the capacitor plates is of a with at least 40 mm and 4. common used frequency generators or field intensities are applied. Reported results suggest to investigate whether the high frequent electrical field influences the fracture regeneration advantageously.


Hemosuccus pancreaticus (hemoductal pancreatitis): gastrointestinal hemorrhage due to rupture of a splenic artery aneurysm into the pancreatic duct. A patient with recurrent upper gastrointestinal bleeding was found to have pancreatitis and a pseudoaneurysm of the splenic artery that communicated with the pancreatic duct. Similar pathology noted in ten other patients found in an extensive review of the literature suggest that this rare entity must be considered in the diagnosis of gastrointestinal hemorrhage of obscure origin. In this collected experience, the combination of recurrent left upper quadrant pain, a history of pancreatitis, and recurrent bouts of gastrointestinal bleeding of obscure origin were usually present in those patients who were found to have a splenic artery aneurysm as the source of the blood loss. Distal pancreatectomy with resection of the splenic artery aneurysm is curative.


Hashish smoking and T-lymphocytes.

Hashish smoking and T-lymphocytes. To investigate the effect of long term hashish use on T-lymphocytes we have measured the incorporation of 14C-thymidine by peripheral blood lymphocytes, unstimulated and stimulated by phytohemagglutinin, as well as the proportion and number of E-rosettes in 12 healthy male chronic users of the drug before and after a smoking session, and in 15 control subjects. The results show that hashish smoking does not impair the response of lymphocytes to PHA, at least at the concentration of PHA used. Furthermore there is a possibility that among chronic users a hashish smoking session may have a slight stimulatory effect.


[Internal carotid artery thrombosis in the course of rheumatic disease. Report of a case]. The case of a 21 years old man with hemiplegia and hyperthermia of sudden onset is reported. The angiographic study showed thrombosis of the distal portion of the internal carotid artery. Laboratorial studies revealed positive rheumatic tests. The authors think that the rheumatic arteritis may be responsible for this ischemic cerebral accident. Differential diagnosis with the embolic accidents caused by the rheumatic disease is discussed.


Endophthalmitis after trabeculectomy.

Endophthalmitis after trabeculectomy. Two cases of late endophthalmitis after trabeculectomy surgery are described. Despite intensive antibiotic therapy, the visual end result in both cases was poor. The incidence of endophthalmitis after trabeculectomy, according to this report is similar to that after Scheie's procedure, but less than that after trephination. A possible cause of endophthalmitis is the anterior dissection of the superficial scleral flap into the cornea.


Hearing disorders after Haemophilus influenzae meningitis. Comparison of different drug regimens. Of 131 children with bacteriologically verified Haemophilus influenzae meningitis, 75 were treated with ampicillin sodium and 45 with a combination of chloramphenicol, sulfonamides, and penicillin G sodium during the first 72 hours. Audiological and neuro-otologic examinations performed 1 to 15 years later showed that 3 patients were totally deaf, 11 had moderate and 15 minimal hearing losses, and 6 had vestibular disorders. All three deaf children and all those with recognized vestibular disorders had been treated with ampicillin. The severe sequelae, both otologic and nonotologic, tended to occur in children of the lower social groups. There were 15 ears with moderate hearing loss; the lesion was cochlear in nine and retrocochlea in four; it could not be localized in two. Ampicillin was given in relatively low dosage, but the results strongly support the value of chloramphenicol of "triple therapy" as weapons against H influenzae meningitis.


The significance of serial measurement of serum anti-native DNA antibodies and complement C3 and C4 components in the management of patients with systemic lupus erythematosus. Serial measurements were made over a period of three years of serum DNA-binding capacity and complement C3 and C4 levels in parallel with documentation of clinical features of disease activity in Glasgow patients with SLE. Raised DNA-binding levels were noted in 27 of the 32 patients over this time period. High levels (over 80%) were found in patients with both renal and non-renal disease. In some patients increases in DNA-binding capacity and decreases in C3 levels were associated with changes in disease activity. This pattern was commonest in patients with renal SLE. In others DNA-binding capacity was elevated without any relationship to SLE disease activity. A fall in serum C3 levels was usually significant while serum C4 levels frequently fell without any change in clinical features of disease activity. Very low serum C4 levels (below 15 mg/dl), however, were usually of clinical relevance. The uses of immunological measurements in the differential diagnosis of a major illness in a patient with SLE are discussed. The finding of such an illness in a patient with normal serum DNA-binding levels made it unlikely that the illness was due to an exacerbation of the SLE and more likely that an alternative cause such as supervening bacteraemia was responsible.


Vestibular disease, and its relationship to facial paralysis in the horse: a clinical study of 7 cases. The signs observed in 6 cases of peripheral vestibular disease included incoordination, head tilt and nystagmus. The intensity of the signs varied greatly with duration of the disease, and in 3 cases facial paralysis was also present. Tympanosclerosis was demonstrable in all cases subject to radiology. Trauma was the causative factor in most cases. The causes of, and relationships between, vestibular dysfunction and concomitant facial paralysis are discussed. The exact etiology of the tympanosclerosis is unknown.


Thresholds of perception for periodic linear motion. This paper reviews 18 reports which have investigated the absolute threshold of perception of periodic linear motion. The roles of the otolith, somatosensory, and visual detection mechanisms in determining threshold are discussed. Most threshold data for oscillation at frequencies below 1 Hz reflect otolith and somatosensory detection, and show a falling threshold as the frequency rises. This is in accord with neurophysiological data of otolith and somatosensory function. The data for frequencies above 1 Hz reflect an unknown mix of visual, otolith, and somatosensory influences. These data are too heterogenous to indicate whether threshold rises or falls as the frequency of stimulation increases.


Effect of the anti-estrogen, Nafoxidine, on NZB/W autoimmune disease. Treatment of female NZB/W F1 mice with Nafoxidine, an anti-estrogen, led to delayed manifestation of autoimmune features. Such treated mice had reduced anti-DNA antibodies, reduced proteinuria, and improved survival. These results support the hypothesis that sex hormones play an important role in the expression of autoimmunity and suggest that estrogens may accelerate autoimmunity in NZB/W F1 mice.


[Muscle metabolic state in tourniquet syndrome in the rat after administration of the proteinase inhibitor aprotinin (author's transl)]. The metabolic status of rat skeletal muscle was examined after 5 h of unilateral ischemia of one hind leg and following 5 h of recirculation. There was no recovery, neither with nor without aprotinin (Trasylol) in different doses (35 000 and 125 000 KIE/kg b.w.). After 3 h of ischemia and 3 h of recirculation a significant recovery of the metabolic status occurred in animals without and with 35 000 KIE aprotinin/kg b.w. After injection of 125 000 KIE aprotinin the restoration of the metabolic status was significantly retarded. The metabolic situation of the contralateral, non-ischemic legs revealed--in comparison to normal levels--a significant deterioration in the latter group.


Technical considerations in patients undergoing combined aortic valve replacement and aortocoronary bypass surgery. Forty-nine patients have undergone combined aortic valve replacement and aortocoronary saphenous vein bypass graft surgery using a technique of distal coronary perfusion. Vein grafts are placed before replacement of the aortic valve, and continuously perfused by siting the proximal anastomoses high on the aortic root or individually perfusing the grafts before proximal anastomosis. Continuous coronary ostial perfusion is used as well during aortic valve replacement. There were 3 (6.1%) operative deaths and 1 (2%) perioperative myocardial infarction. A comparison of this technique with other reported results suggests that attention to myocardial perfusion distal to significant coronary artery stenosis may decrease the incidence of perioperative myocardial infarction in patients requiring both aortic valve replacement and coronary bypass graft operation.


Effect of adult thymectomy on tumour immunity in mice. The effect of adult thymectomy in DBA/2J mice on the in vitro response to syngeneic tumour cells was investigated. Spleen cells from adult mice which had been thymectomized 8 weeks previously demonstrated a severely impaired primary cytotoxic response to P815 tumour cells, whereas their cytotoxic responses to allogeneic cells (C57BL/6) and to non-H-2 antigens (BALB/c), and their ability to form a primary antibody response to sheep red blood cells was unimpaired. Suppressor T cells, specific for P815 cells, appeared early in the thymuses of animals inoculated with P815 cells (between 4 and 8 days after tumour-cell injection). No differences in tumour growth between animals thymectomized as adults and sham-operated controls were observed, and thymectomized tumour-bearing animals had levels of specific suppressor cells in their lymph nodes equivalent to the levels found in untreated controls. Severely thymocyte-deprived animals which had been thymectomized, irradiated and reconstituted with either marrow or spleen cells 8 weeks before tumour implantation succumbed more rapidly to metastatic tumour than did control animals.


Activity and stability of the luciferase--flavin intermediate. A luciferase intermediate in the bacterial bioluminescence system, which is formed by reaction of enzyme with reduced flavin mononucleotide (FMNH2) and oxygen, is shown to emit light with added aldehyde under anaerobic conditions. The reaction with oxygen is thus effectively irreversible under the conditions used. The flavin chromophore has an absorption maximum at about 370 nm and the potential activity (bioluminescence yield) in the further reaction of the isolated intermediate with aldehyde is strictly proportional to the amount of this flavin chromophore.


Formation and development of photosynthetic units in repigmenting Rhodopseudomonas sphaeroides wild type and "Phofil" mutant strain. The formation of the photosynthetic apparatus in the wild type Rhodopseudomonas sphaeroides and in the "Phofil" mutant was investigated by analyzing absorption and fluorescence parameters and the kinetics of fluorescence induction. Repigmentation was induced by transfer of bleached cells to semi-aerobic culture conditions. 1. In the "Phofil" mutant, functional photosynthetic units appear at pigment cellular contents which depend on the physiological state of the inoculum. The unadapted mutant can reach the functional units stage at a cellular pigment level 20 times lower than that of the wild type, although the size and composition of the units are identical in both strains. This rules out the hypothesis of photosynthetic units forming by random integration of pigments into the membrane. Moreover, the fact that units are separate at this stage (as shown by the exponential shape of fluorescence induction kinetics) suggests that the units' formation proceeds from discrete predetermined membrane sites. 2. In repigmentng wild type cells, the multistep assembly of bacteriochlorophyll complexes appears correlated to their organization in photosynthetic units as follows: (i) During a first stage, B-875 is mostly synthesized, while the efficiency of transfer increases, suggesting that the pigments are initially interpersed at comparatively large average distances from each other in the bleached membrane. (ii) After 1.5 h of repigmentation, the transfer and trapping efficiencies reach a maximum. The units (26 B-875 + 11 B-850 per center) are still separate, as shown by exponential fluorescence kinetics. (iii) The increase in the units' size then essentially proceeds through B-850 incorporation. Energy transfer between units occurs at a comparatively late stage, i.e., 5 h repigmentation.


Electron transfer and spin exchange contributing to the magnetic field dependence of the primary photochemical reaction of bacterial photosynthesis. The yield phiT of triplet products "PR" generated in reaction centers of Rhodopseudomonas sphaeroides in which the "primary" acceptor is reduced had been found to depend on external magnetic fields. The magnetic field dependence varies, however, between different reaction center preparations. By means of a theoretical description of the primary electron transfer processes and hyperfine coupling-induced electron spin motion the factors influencing the magnetic field behaviour of the triplet products are studied. The following quantities characteristic of the primary electron transfer in photosynthesis have a strong effect on phiT: (1) the rate constants of reversible electron transfer between the initially excited singlet state of the reaction center and an intermediate radical ion pair state; (2) the rate constants of irreversible electron transfer of the radical pair to the ground and excited triplet state of the reaction center; (3) the electron exchange interactions between the radical pair and the "primary" acceptor. From the observed magnetic field dependence of phiT estimates for these quantities are obtained. A temperature dependence of the magnetic field behaviour of phiT and a magnetic field effect on the fluorescence quantum yield of the reaction center are predicted.


Analysis of the pigment content of an antenna pigment-protein complex from three strains of Rhodopseudomonas sphaeroides. The pigment content of a B800-850 light-harvesting pigment-protein complex isolated from three different stains of Rhodopseudomonas sphaeroides has been determined. In each case the ratio of carotenoid to bacteriochlorophyll present is very nearly 1 : 3 an no specificity with regard to carotenoid type was observed. The fourth derivative of the infra-red absorption bands of the complex was determined and it is concluded that the minimal functional unit of B800-850 complex consists of 1 carotenoid molecule and three bacteriochlorophyll molecules. The data presented here, together with the previous study of Austin, (Austin, L.A. (1976) Ph.D. Thesis, University of California at Berkeley, Lawrence Berkeley Laboratory Report No. LBL 5512) suggest that the 800 nm absorption band represents one of these bacteriochlorophyll molecules while the remaining two bacteriochlorophylls are responsible for the 850 nm band. The absorption spectra and circular dichroism spectra of the complexes suggests that their structure has not been greatly altered during the purification.


Short circuit current in tight and leaky epithelia. The effect of short circuit current on the unidirectional fluxes of ions transported across tight and leaky epithelia was investigated. It was found that short circuiting of the frog gastric mucosa (classified as a tight epithelium) caused a decease of the passive JClms and a significant increase of the net Cl- secretion. However, no significant change of H+ secretory rate was observed. On the other hand, short circuiting of the mouse intestine (a known leaky membrane) caused a simultaneous increase of both Jms and Jsm fluxes of Na+ while the net fluxes of Na+ and Cl- remained unchanged. Also, short circuiting did not change the water permeability of the mouse intestine. To explain some of these results a theoretical model is presented to demonstrate that while short circuiting can block the passive ionic movement, it will cause an increase in the energy consumption of the system and introduce certain important changes in the ionic barriers and e.m.fs. The simultaneous increase in the unidirectional fluxes of Na+ under short circuit conditions can best be explained by a decrease in the polarized nature of the transepithelial shunt, thereby increasing the diffusion coefficient of the ion(s). Such an increase is specially favorable to the Na+ rather than an anion.


Circular dichroism studies on the effects of ethanol on the conformation of alpha1-acid glycoprotein, alpha1-antitrypsin, deoxyribonuclease, pepsinogen, soybean trypsin inhibitor and unfolded ribonucleases. The effects of 25 to 75 volume-% ethanol on conformation of human serum alpha1-acid glycoprotein, human serum alpha1-antitrypsin, pancreatic deoxyribonuclease I, porcine pepsinogen, the "Kunitz" trypsin inhibitor from soybeans, and oxidized as well as reduced and S-carboxymethylated ribonucleases were tested by the circular dichroism (CD) probe. It was found that 25 volume-% ethanol had a slight effect, whereas 50--75 vol.-% alcohol significantly altered the conformation. The tertiary structure was perturbed and the polypeptide main chain was reorganized into new conformations of higher helix and beta-structure contents than in the native state. Comparison of the various proteins showed that the degree of reorganization depended chiefly on the cross-linking of the main chain by disulfide bridges. While the unfolded ribonucleases were refolded by 25 vol.-% ethanol into ordered conformations, the native ribonuclease and alpha1-antitrypsin was more sensitive to 25 vol.-% ethanol than the conformation of alpha1-acid glycoprotein, pepsinogen, and soybean trypsin inhibitor. Almost complete restoration of the native conformation was achieved by diluting the alcohol-containing solutions with water or by dialysis against water or buffer solutions. However, the renaturation depended on the time of contact with alcohol and on the temperature at which the alcohol-containing solutions were kept.


Helicoids in the T system and striations of frog skeletal muscle fibers seen by high voltage electron microscopy. Reconstruction from thick serial transverse slices of frog skeletal muscle fibers stained with peroxidase and examined by high-voltage electron microscopy has revealed that the T system networks at successive sarcomeres are connected together in a helicoidal fashion. From zero to eight helicoids have been found in each of a group of 21 fibers reconstructed in cross section. Helicoids can have either right- or left-handed screw senses, and both senses can be found in one fiber cross section. Because the T system maintains a relatively precise alignment with the myofibrillar striations, it follows that the striations must also have a helicoidal arrangement. This has been found before, but has not been widely accepted in recent times. The presence of helicoids in the bands and membrane networks is not thought per se to alter very much our thinking about excitation and contraction mechanisms in skeletal muscle fibers.


[Contracture of the myocardial fibers of the frog ventricle after high frequency stimulation while the calcium channels were blocked by manganese ions]. The contractile force of the myocardial strip of the frog ventricle stimulated by impulses of 0.5 Hz was diminished to 3--5% of the initial value when perfused with Ringer's solution containing 2.5 mM manganese. Under this condition the action potential duration was significantly decreased. An increase in frequency of stimulation up to 5 Hz leads to the development of contracture. The amplitude of contracture was about 30% of the initial contractile force in normal perfusion solution. The amplitude of contracture was more than doubled under the effect of ouabain (2 X X 10(-6) g/ml). Similar experiments with lanthanum failed to discover contracture produced by the increase of the stimulation frequency. In these experiments ouabain was also ineffective. It is supposed that contracture observed in the presence of manganese was caused by nonelectrogenic calcium transport into the muscle fibers.


[Simultaneous detection of T-, B- and D-rosette forming lymphocytes and null cells in humans]. For the identification of T-, B-, and D-rosette-forming lymphocytes and the "null" cells in the human peripheral blood a simultaneous reaction of rosette-forming cells with the use of zymosan-complement, sheep red blood cells, fixation and staining of smears in extraction of the lymphocytes tested with the aid of verographin may be recommended.


[Ultrastructure of the conjugates of cytolytic T-lymphocytes and target cells]. Conjugates of target cells and of cytological T-lymphocytes obtained on the 11th day after alloimmunization were investigated. The conjugates formed small and medium lymphocytes; mature secretory granules, crystal-like structures and lipids were revealed in their cytoplasm. The lymphocyte is spherical, the area of contact with the target cell does not exceed 5 to 15%. Cytolysis of target cells is observed after 30 to 60 minutes of incubation. The lymphocyte becomes flattened, its nucleus acquires an oval form, and the area of contact with the target cell increases considerably. At the same time hypertrophy and change of orientation of Golgi's complex to the area of contact with the target cell, coalescence of the secretory granules with lipids and crystal-like structures, the appearance of immature secretory granules and vacuolar degeneration of mitochondria are demonstrated. The lymphocyte membrane becomes "desquamated"; structures connected with it, named "membranosomes" are described. It is suggested that the secretory processes in the cytoplasm of cytolytic T-lymphocytes are activated in their interaction with target cells.


[Thymosin activation of T-killer precursors for hematopoietic stem cells]. Lymph node cells of normal CBA mice, syngeneic radiation chimerae CBA leads to CBA and B-mice after incubation with thymosin (fraction 5) were transplanted to sublethally irradiated recipients (CBA X C57BL) F1; the number of endogenic colonies in the recipient's spleen was then recorded. Thymosin was shown to increase the killer activity of the lymph node cells of normal mice CBA, syngeneic chimerae CBA leads to CBA, but not of B-mice. As suggested, TU-cells' subpopulation served as target cells for thymosin.


Clinical and cell surface marker characterization of the early phase of chronic lymphocytic leukemia. The immunologic surface markers on lymphocytes and clinical characteristics of 35 patients with established (stages 0-4) CLL with absolute lymphocyte counts greater than 15,000/cu mm were compared to those of a group of 25 patients with CLL in an early or preleukemic phase (counts of less than 15,000/cu mm). We found a monoclonal B cell proliferation in most cases in the latter group, in spite of the paucity of clinical and laboratory findings. Furthermore, early CLL can readily be distinguished from benign lymphocytosis by surface marker criteria. In untreated CLL, surface marker characteristics are stable with time and predominantly reflect expansion of clones expressing only B cell markers; however, small increase of blood T cells are often seen. Surface markers are a simple and clinically useful tool for definding and characterizing the preleukemic phase of CLL and its ultimate progression to established CLL.


T cell chronic lymphocytic leukemia: presence in bone marrow and peripheral blood of cells that suppress erythropoiesis in vitro. The pathogenesis of the anemia associated with malignancy was investigated in a patient with T cell chronic lymphocytic leukemia. The plasma clot culture system was used as a measure in vitro of erythropoiesis. The patient's peripheral blood and marrow T lymphocytes obtained both before and after transfusion therapy suppressed erythroid colony formation by normal human bone marrow cells. Pretreatment of the patient's bone marrow T cells by antithymocyte globulin (ATG) and complement reversed this suppression. In addition, pretreatment of the patient's marrow cells with ATG and complement markedly augmented erythropoiesis in vitro. The expression of erythroid activity caused by the selective destruction of the suppressor T lymphocytes in the patient's bone marrow with ATG and the suppression of normal erythropoiesis by the patient's bone marrow and peripheral blood lymphocytes suggest that interaction between the malignant T cell and the erythropoietin-responsive stem cell is important in production of anemia in this patient.


Surface glycoproteins of human white blood cells. Analysis by surface labeling. We labeled surface glycoproteins of normal human blood platelets, granulocytes, monocytes, T and B lymphocytes, and null cells by the galactose oxidase-NaB3H4 and periodate-NaB3H4 labeling techniques. The labeled glycoproteins were observed by fluorography after separation by polyacrylamide slab gel electrophoresis. All major types of human leukocytes showed different and characteristic surface glycoprotein patterns. These patterns evidently also include common components.


Clonal origin of a T cell lymphoproliferative malignancy. A woman with a T cell lymphoproliferative malignacy and heterozhgosity at the X chromosome-linked locus for glucose-6-phosphate dehydrogenase (G-6PD) isoenzymes was studied to find the clonal origin of her circulating neoplastic T cells. The red blood cells, polymorphonuclear cells, whole mononuclear cells, and T cell-depleted mononuclear cells contained both A and B isoenzymes of G-6-PD. In contrast, the tumor cells, separated by using their capacity to form rosettes with sheep red blood cells, contained only the B isoenzyme of G-6-PD. This observation strongly suggests the monoclonality of this T cell malignancy.


Pokeweed mitogen-induced B cell differentiation in idiopathic aplastic anemia associated with hypogammaglobulinemia. Peripheral blood lymphocytes from 14 patients with idiopathic aplastic anemia were examined to determine their capacity to differentiate into immunoglobulin (lg) producing cells in the presence of pokeweed mitogen (PWM). Four patients had hypogammaglobulinemia. Lymphocytes from ten patients without and one with hypogammaglobulinemia were capable of differentiating into lg-producing cells. Lymphocytes from three patients with hypogammaglobulinemia, however, were unable to differentiate. Coculture experiments showed that in one patient helper activity of T cells was impaired, in another patient B cells could not be stimulated by PWM to differentiate even in the presence of normal T cells, and in a third patient both the helper function of T cells and the capacity of B cells to differentiate into lg-producing cells were affected. These results suggest that differentiation of lymphoid cells is impaired in some cases of idiopathic aplastic anemia associated with hypogammaglobulinemia.


Comparison of enzyme-cytochemical findings and immunological marker investigations in acute lymphatic leukemia (ALL). APh-activity and PAS-positive deposits were studied in 50 cases of ALL, classified as T-ALL and O-ALL according to immunological marker investigations. Correlation between morphological features of the cells and APh and PAS reactions, as well as between morphology and immunological markers was not detected. APh-activity in general was stronger in T-ALL (R+ and R-), while PAS-content was more pronounced in O-ALL. The results suggest that cytochemical methods, especially APh and PAS reaction, are valuable to distinguish T-ALL from O-ALL but not reliable enough to replace immunological marker investigations.


Functional and surface characterisitics of lymphocytes from patients with warm-antibody type autoimmunhemolytic anemia (AIHA). As part of an overall assessment of immunological function, several aspects of cellular immunity and circulating lymphocyte subpopulations were evaluated in a group of 10 patients with idiopathic autoimmunhemolytic anemia (AIHA). The absolute numbers of circulating T and B cells were reduced in the patient group compared to normals. A shift from "corticosteroid-sensitive" to "corticosteroid-resistent" and activated cells in the cytogram of clustered Fe-(III)-hydroxide-glucane saccharose labeled T lymphocytes was apparent. In vitro studies of cellular reactivity, as evaluated by PHA, ConA, PWM, antigens and allogeneic cell induced proliferation showed a blend of general or selective depression and sometimes a normal or increased activity with no definite correlation with both the number of circulating T cells and the extent of the hemolytic activity by the disease. The possible significance of the findings is discussed.


[High-dose methotrexate/leucovorin adjuvant chemotherapy of osteogenic sarcoma: biochemical effects in DNA-synthesis of bone marrow cells (author's transl)]. DNA metabolism in bone marrow cells was measured under high-dose Methotrexate/Leucovorin adjuvant chemotherapy of a patient with primary amputation of his right leg because of osteogenic sarcoma. The biochemical data showed that there was no rescue effect of Leucovorin after 200 mg/kg Methotrexate. Corresponding to this "biochemical failure" of the rescue effect the patient died from the complications of a long and very severe bone marrow suppression. To improve the safety of this therapeutic regimen the intravenous injection and in some cases a higher dose of Leucovorin is recommended.


[T-cell-antigen positive, E-rosette negative acute lymphoblastic leukaemia (author's transl)]. The lymphoblasts from 100 patients with acute lymphocytic leukaemia were investigated for the expression of receptors for sheep erythrocytes (E) and of a specific heterologous T cell antigen (T). In 17 cases, both T cell markers were expressed simultaneously on the leukaemic cells. In 13 cases only T antigens could be demonstrated on the lymphoblasts. A quantitative analysis of T antigens by immunoautoradiography revealed that the T expression of E-T+ -lymphoblasts was in general like that of E+T+-lymphocytes in the blood of normal persons, in several cases even higher. Therefore, the failure of E-rosette formation cannot be correlated to a decrease of the other T cell differentiation marker. In 7 out of 9 tested cases, a strong acid phosphatase reaction product located paranuclearly could be demonstrated. Complement-receptors were expressed in 3 of 5 cases which were also demonstrated in some cases of the E+T+-ALL group. The latter group was characterized by a T antigen expression like that of thymocytes. 4 cases of the E-T+ALL group were adults. Since the leukaemia cells of 2 cases were negative for acid phosphatase, PAS and all surface markers including cALL antigen, the T antigen can classify undifferentiated and otherwise unclassificable leukaemias. The clinical signigicance of the E-T+-ALL seems to be important since 5 out of 9 children with this type of ALL died soon after diagnosis.


Absence of detectable local antibody in genitourinary tract secretions of male contacts of women infected with Trichomonas vaginalis. Samples of semen and urine were obtained from 37 male contacts of women with proved Trichomonas vaginalis infection; on culture, eight (22%) of the men were shown to harbour the parasite. However, significant amounts of antitrichomonal antibody were found in only two of these samples, and the amounts present were very small. A further 10 samples were tested but none was found to contain antibody. The asymptomatic nature and low parasite numbers commonly described in infections in men is thus unlikely to be due to a vigorous local immune response.


Serum epinephrine and norepinephrine during valve replacement and aorta-coronary bypass. A comparison of the levels of serum epinephrine, norepinephrine and blood pressure was made in 25 patients undergoing aorta-coronary bypass or valve replacement who were anaesthetized with a nitrous oxide-narcotic technique. Serum epinephrine and norepinephrine were measured in arterial samples drawn pre-induction, post-induction, before cardiopulmonary bypass, two and eight minutes after initiation of cardiopulmonary bypass, 20 minutes before termination and after termination of cardiopulmonary bypass. In both patient groups significant increases in epinephrine and norepinephrine occurred befored cardiopulmonary bypass, with accompanying increase of blood pressure in the valve replacement patients. During cardiopulmonary bypass an initial hypotensive response (p less than 0.001) was recorded, followed by a significant increase in blood pressure and epinephrine in both groups. After cardiopulmonary bypass, aorta-coronary bypass patients had epinephrine, norepinephrine and blood pressure equal to levels before cardiopulmonary bypass. In contrast, serum epinephrine continued to rise in the valve replacement patients, with a gradual recovery of blood pressure to pre-bypass levels. These findings demonstrate significant differences in blood pressure and catecholamine response in patients with valvular disease from patients with coronary artery disease.


Anaesthesia for the carcinoid syndrome: a report of nine cases. Anaesthesia for nine patients with the carcinoid syndrome is described. With the exception of one case in which severe bronchospasm and hypertension occurred, complications were minor. Steroids, aprotonin and methotrimeprazine appear to be useful agents in the management of such patients. An anaesthetic technique employing thiopentone, pancuronium and nitrous oxide proved satisfactory.


Alpha1-antitrypsin phenotypes and lung function in a moderately polluted northern Ontario community. To determine whether persons with intermediate value alpha1-antitrypsin phenotypes living in a polluted environment manifest significant abnormalities in lung function, a study was undertaken of an age-, sex- and smoking-stratified sample of 391 persons from the town of Fort Frances, Ont., which has elevated values of total dustfall, suspended particulates and hydrogen sulfide. Indices of pulmonary function were derived from the maximum expiratory flow and the single breath expiratory flow and the single breath expiratory nitrogen washout curves. The percentage frequency of the M, MS and MZ pheontypes was 91.7, 7.3 and 0.8, respectively. There was no significant difference between the M and MS groups as indicated by the nitrogen washout curve and maximum expiratory flow curve. There was no significant difference between the three MZ subjects and the M group. In both M and MS groups smokers displayed evidence of airflow obstruction when compared with nonsmokers. It would appear that, when compared with M subjects, persons with the MS phenotype living in a moderately polluted area show no changes in indicators of pulmonary function, including tests of early airway disease, that cannot be attributed to their smoking habit.


A prospective study of immune responsiveness in human melanoma. I. Assessment of initial pretreatment status with stage of disease. The clinical findings in 262 patients with melanoma were correlated with an assessment of their cellular-mediated immunity by delayed-type hypersensitivity (DTH) skin tests, by lymphocyte blastogenesis, and by leukocyte enumerations. Patients with systemic metastases (stage IV) and those with evidence of tumor burden had fewer positive DTH reactions for recall antigens than did patients with localized disease (stage I), patients with no evidence of tumor burden, and 227 normal controls. However, no differences were found in the magnitude of response among patients with melanoma or when compared with controls. Patients with melanoma had fewer responses to dinitrochlorobenzene (40% than did controls (98%), but there were no differences by stage or tumor burden. Similarly, blastogenesis in the presence of PHA, Con A, and PWM was depressed when compared with controls, but there was no meaningful correlation with the clinical status. Leukocyte, T cell, or B cell counts revealed no alteration from normal for the patients with melanoma. The usefulness of these studies for routine clinical monitoring is questioned.


Thymoma: an immunologic and electron microscopic study. Ultrastructural features, surface morphology and immunologic surface markers were examined on the cells of three human thymomas. The vast majority of the lymphocytes from the thymomas formed spontaneous rosettes with unsensitized sheep erythrocytes in both cell suspension and frozen tissue section and were, therefore, T cells. In addition to the lymphocytes, epithelial cells and macrophages were observed within the thymomas by transmission electron microscopy. When examined by scanning electron microscopy, most lymphocytes had virtually smooth surfaces, whereas cells believed to be epithelial in origin had surface projections.


Aryl hydrocarbon hydroxylase activity in subpopulations of peripheral blood mononuclear cells. Peripheral blood mononuclear cells (PMC), isolated by density gradient techniques with Ficoll-Hypaque, contain T- and B-lymphocytes and monocytes. Aryl hydrocarbon hydroxylase (AHH) activity was measured in PMC subfractions consisting of T-lymphocyte-enriched, T-lymphocyte-depleted, and monocyte-depleted populations. The T-cell-enriched populations consistently showed enhancement of AHH activity with both the fluorometric and radiometric technique when compared to the total PMC population. This enhanced AHH activity was observed when T-cell-enriched populations were isolated either before or after 96 hr of lymphocyte culture, by the sheep red blood cell rosette method, or by the nylon wool column technique before lymphocyte culture. T-cell-depleted populations (B-cell enriched) obtained by sheep red blood cell rosette method had diminished AHH activity. Monocytes were shown to contribute to the total PMC AHH activity through an indirect technique by first depleting the monocytes from PMC with the carbonyl iron method. The monocyte-depleted populations had less AHH activity than did the total PMC population after both 24 and 96 hr of culture. The greatest amount of AHH activity was present in PMC populations with their native number of monocytes when cultured for 96 hr in the presence of mitogens.


Risk factors and mortality in patients with aortocoronary vein bypass operation. Patients who died one or more years after aortocoronary bypass surgery showed, at the time of the operation, higher prevalence of hypertension, and history of smoking and had higher plasma lipid levels than the patients who survived the operation for similar periods of time. No such differences in risk factors were seen between patients who survived or have died during the first 30 days after the operation. These findings suggest that pateints with abnormal risk factors have a poorer long-term prognosis.


Lack of DNA synthesis inhibitory activity in an immunosuppressor obtained from spleen. A tissue extract derived from bovine spleen which is an immunosuppressor in vivo inhibits the incorporation of the two DNA pyrimidine nucleosides but does not inhibit the incorporation of purine nucleosides. The results indicate that the immunosuppressive action of the spleen extract is not mediated via inhibition of cell division.


Two plasma membrane antigens of testicular sertoli cells and H-2-restricted versus unrestricted lysis by female T cells. Sertoli cell-only seminiferous tubules of sterile XX,Sxrl-male mice served as an excellent source of pure Sertoli cells. When H-2-compatible female mice were immunized 3 times with these Sertoli cells, resulting antibodies recognized two antigens on the plasma membrane of testicular Sertoli cells. They were male-specific, but ubiquitously expressed H-Y antigen and the cell lineage-specific antigen which Sertoli cells shared with ovarian follicular cells. Doubly primed (2 or 3 times in vivo, and once in vitro) cytotoxic T cells from these females lysed target Sertoli cells in both H-2-restricted and nonrestricted manners. While H-2-restricted killings were attributable to H-Y antigen, further work is needed to identify the Sertoli follicular cell lineage-specific antigen as the cause of H-2-nonrestricted killings.


Amphibian embryo protease inhibitor. V. Effect of calcium on the distribution of amphibian trypsin inhibitor during fertilization and subsequent development of Rana pipiens. In previous publications we have documented the existence in oocytes and embryos of a variety of forms (notably Rana pipiens), massive amounts of a powerful inhibitor of trypsin-like enzymes (ATI). The bulk of the inhibitor in Rana pipiens is localized in yolk platelets. We present evidence here that the distribution of the inhibitor between yolk platelets and cytosol changes and that this change is mediated by variations in the distribution of calcium ions. There is an inverse relationship between ATI and free calcium in the cytosol. Several workers have demonstrated a dramatic rise in free cytosol calcium immediately following fertilization. We confirm this observation, and demonstrate that there is a parallel and equally dramatic decrease in free cytosol ATI during this period. Experiments with purified yolk platelets indicate that calcium effects a release of sequestered inhibitor from these particles. Other experiments indicate that calcium mediates ATI-lippovitellin associations. A calcium mediated flux of ATI from cytosol to yolk is proposed as a device for controlling limited proteolysis in the cytoplasm. We offer this as a model for studying the unmasking of mRNA which follows fertilization.


Supravital excitability of skeletal muscle of rats and bullfrogs to electrical stimuli. Supravital excitability to electrical stimuli (for convenience, supravital electrocontractility (S.Ec) of the gastrocnemius muscle of rats and bullfrogs was examined after "somatic death" and the time during which S.Ec could be detected (S.Ec duration) was measured. S.Ec of the gastrocnemius muscle of rats and bullfrogs depended on temperature. The maximum S.Ec duration of the muscle of rats and bullfrogs were 110 min and 96 hr, respectively, at a low temperature (5 degrees), and 60 min and 9 hr, respectively, at a high temperature (30 degrees). The time course of rigor mortis at 5 degrees was slow and it was rapid at 30 degrees. In rats, the S.Ec disappeared completely before the onset of rigor mortis, and in bullfrogs, S.Ec existed at progressive stages of rigor mortis and it disappeared completely when rigor mortis reached about the maximum.


Analysis of glucocorticoid metabolites in the neonatal period: catabolism of cortisone acetate by an infant with 21-hydroxylase deficiency. The urinary excretion of 27 individual 17-hydroxycorticosteroids by a female infant with 21-hydroxylase deficiency was studied using gas chromatography on an open-tubular column and combined gas chromatography-mass spectrometry. Samples were analysed from days 1, 3 and 4 of life, before cortisone acetate treatment commenced on day 6, and on days 9 and 192, during treatment. The pattern of metabolites before and after treatment showed similarities with extensive reductions at positions 3 and 20 of the steroid nucleus and hydroxylations at positions 1 and 6. The following new glucocorticoid metabolites were identified: 1beta,3alpha,17alpha,21-tetrahydroxy-5alpha(andbeta)-pregnane-11,20-dione; 3alpha,6xi,17alpha,21-tetrahydroxy-5xi-pregnane-11,20-dione (2 epimers); 1beta,3alpha,17alpha,20alpha(andbeta),21-pentahydroxy-5beta-pregnan-11-one, and 3alpha,6xi,17alpha,20alpha (andbeta),21-pentahydroxy-5beta-pregnan-11-one. These steroids comprised 50% of the total metabolites on day 9, but only 20% on day 192. They have also been detected in the urine of normal neonates.


The association of HLA-B8 with visceral disease in systemic sclerosis. Seventy-one patients with systemic sclerosis (SS) were typed for twenty-seven HLA alleles of the A and B loci, and the findings were related to both the extent of visceral disease and tests of cellular immune competence in a subgroup of fifty-two of these patients. Nineteen pa;ients with widespread visceral involvement and more rapidly progressive disease had an increased frequency of HLA-B8 (relative risk = 4.14; P less than 0.05) when compared to thirty-three less severely affected patients and 3000 controls. Patients with severe and progressive disease also had defective cell-mediated immunity with reductions in both the numbers of circulating thymus-dependent (T) lymphocytes and in the lymphocyte transformation response to phytohaemagglutinin. These findings suggest that a genetic factor, such as an abnormal immune response gene, may be involved in the progression of the disease.


Acute lymphoblastic leukaemia of the B-cell type refractory to intensive chemotherapy. Four patients, aged 15-50, with acute lymphoblastic leukaemia (ALL) shown to be of the B-cell type, since they formed rosettes with complement-coated sheep erythrocytes (EAC) and had lymphocytes bearing IgA on the cell surface. Clinically, they had massive leukaemic infiltration associated with hepatosplenomegaly and were extremely resistant to multiple, conventional chemotherapy, as demonstrated by prolonged therapy to achieve a remission or a short-term remission. The surface characteristics of the lymphoblasts in the circulating blood seemed to remain unchanged throughout the course of the leukaemia, despite intensive chemotherapy. The evaluation of surface markers on leukaemic cells might give better information for a forecast of the prognosis of the disease.


Evaluation of the simultaneous estimation of anti-dsDNA and anti-ssDNA antibodies for clinical purposes. The double-antibody solid-phase assay for DNA antibodies permits simultaneous and quantitative determination of antibodies to dsDNA and ssDNA. Using this method, 170 sera, mainly ANA-positive, were examined for the presence of anti-dsDNA and anti-ssDNA to assess the role of these antibodies in the ANA reaction. It was found that in the SLE group of patients, their ability to respond to dsDNA was correlated with the multiorgan symptomatology of disease. Anti-ssDNA titres are also highest in this group. However, anti-ssDNA titres predominate over anti-dsDNA in other collagen diseases. This predominance increases as we progress from the SLE group to undefined mild collagenosis, because the response to dsDNA decreases more than the response to ssDNA. This observation suggests that the clinical manifestation of the collagen diseases and multiorgan manifestation of SLE is linked with the pattern of response to DNA in the majority of cases. In conclusion, it appears that the determination of both ssDNA and dsDNA antibodies can be of value for the prognosis and management of patients with connective tissue disease.


T-cell depletion and in vitro thymosin inducibility in asthmatic children. Thirty asthmatic children were compared with an equal number of age-matched healthy children. The mean peripheral blood T-lymphocyte level without foetal calf serum was lower in the asthmatic group (mean 970/mm3, as against 1740/mm3; P less than 0.0001), but this difference was abolished by adding foetal calf serum or thymosin, thus explaining how quite severe T-cell deficiency can be missed by widely used methods. The degree of eosinophilia and the degree of elevation of the plasma IgE level in the asthmatic patients were positively correlated. Positive correlations were also shown between the degree of severity of the asthma, the degree of eosinophilia and the degree of elevation of the plasma IgE level, but not the degree of depression of the T-cell numbers. If this T-cell deficiency reflects an inadequate suppression of IgE responses, a clinical trial of thymosin appears to be warranted.


Glyceryl p-aminobenzoate patch testing in benzocaine-sensitive subjects. Benzocaine-reactive patients were patch tested to two commercial sources of glyceryl p-aminobenzoate containing varying concentrations of benzocaine as a contaminant. Eleven of 20 reacted to the source with approximately 0.3% benzocaine; none reacted to the source with approximately 0.001% benzocaine.


Recent applications of functional electrical stimulation to stroke patients in Ljubljana. Functional movements can be restored after stroke by portable neuroelectric stimulator controlled by the patient. This field of activity is called functional electrical stimulation (FES). A common example of FES is electric stimulation of the peroneal to prevent dropfoot. A more sophisticated multichannel enables stimulation of more than one paralyzed muscle of the leg. This system is used temporarily to facilitate recovery of muscle function following stroke. Upper extremity FES systems have proven more difficult to develop than lower extremity systems designed to improve walking. A single-channel hand stimulator is available to assist finger movements.


Selective IgA deficiency and Pi ZZ-antitrypsin deficiency. Association with recurrent sinopulmonary infections, emphysema, and bronchiectasis. We describe a patient in whom selective IgA deficiency and homozygous alpha1-antitrypsin deficiency were discovered. Clinically, the patient suffered from chronic sinopulmonary infections, destructive emphysema, and bronchiectasis. The interrelation of IgA and alpha1-antitrypsin was studied. Twenty-three alpha1-antitrypsin-deficient sera were screened for IgA deficiency. None of these sera were deficient in IgA. Fifteen IgA-deficient sera were screened for alpha1-antitrypsin deficiency. In this group, three patients were found to have variant alpha1-antitrypsin phenotypes. Respiratory infections were a prominent complaint in all three of these patients, with bronchiectasis in two patients. We believe that the combination of IgA and alpha1-antitrypsin deficiencies should be considered in the evaluation of any patient with idiopathic bronchiectasis.


Hormonal factors concerned with liver regeneration. Hepatic regeneration in partially hepatectomized, eviscerated rats, and survival in mice infected with lethal doses of murine hepatitis virus, are both strikingly promoted by combined administration of insulin and glucagon. These two hormones, although potent promotors, fail as initiators of hepatocyte proliferation in animals with intact liver, which suggests a requirement for additional factors, probably derived from non-portal-splanchnic organs. We now find that continous intraperitoneal infusion of epidermal growth factor (EGF) initiates DNA synthesis, as determined by incorporation of [3H] thymidine, in livers of adult rats in vivo. The rise in DNA labelling, which is small with EGF alone, is augmented by addition to the infusion of either glucagon or insulin. This is in agreement with reports on adult hepatocytes in culture. Whether EGF has a physiological role in regulating liver growth under normal conditions in vivo remains to be determined.


Abnormal blood vessels of the prepyloric antrum in cirrhosis of the liver as a cause of chronic gastrointestinal bleeding. Three elderly females presenting with iron deficiency anaemia and faecal loss of blood were found to have a macronodular cirrhosis of the liver and an unusual red spotty appearence of the prepyloric antral mucosa. One patient underwent antral resection and the surgical specimen revealed abnormalities of the (sub)mucosal blood vessels. Anaemia and occult faecal blood loss disappeared after operation. It is suggested that this type of antral vascular abnormality is aetiologically related to hepatic cirrhosis and may represent a gastric equivalent of cutaneous spider angiomata.


Distribution of cardiac output in burned mice after treatment with triglycylvasopressin. Earlier published results have shown an increased 5-day survival in burned mice treated with Triglycylvasopressin. In order to analyze the  cause of the increased survival, the distribution of cardiac output was studied in 51 mice divided into three groups. The investigation was performed on the 5th day after burn using a soluble indicator technique (86Rb). The first group consisted of unburned animals. In the second and third groups, a standardized burn of 15% of the body surface was undertaken. The animals in the second group were used as controls and received isotonic saline solution for 5 days. The third group were used as controls and received isotonic saline solution and in addition Triglycylvasopressin, a vasopressin with prolonged effect, 100 microgram/kg body weight subcutaneously twice a day in such a way that the total volume of fluid was identical in the different groups. Cardiac output distribution showed an increased fraction to kidney, liver and small bowel and a decreased fraction to carcass in the Triglycylvasopressin-treated animals compared to burned controls.


Human B cell differentiation. I. Immunoglobulin synthesis induced by Nocardia mitogen. Nocardia water-soluble mitogen (NWSM) is a mitogen which activates human B lymphocytes even in the absence of T cells. Tonsil and peripheral blood lymphocytes cultured in the presence of NWSM gave rise to large numbers of cells containing cytoplasmic immunoglobulins of IgM, IgA or IgG classes. The number of plasma cells appeared to be elevated as early as day 3 of culture and peaked on day 5 or 7. The IgM response preceded the development of cells containing other Ig classes, and was found to remain predominant on days 5 and 7. A similar number of plasma cells were generated in T-deprived suspensions; however, a quantitative regulation by T cells cannot yet be excluded. The response to pokeweed mitogen appeared to be similar, except that it was often less intense and not observed in the absence of T cells. Very few or no IgD-containing cells were found to be differentiated with both mitogens.


Role of adherent cells in immune responses to phytohemagglutinin and concanavalin A. The roles of adherent and nonadherent T cells in the responses to phytohemagglutinin (PHA) and concanavalin A (Con A) were studied. [3H]thymidine uptake by mononuclear cells from human thymus and peripheral blood was used to measure the relative influence of monocytes and B cells on the responses to these mitogens. The response to Con A was dependent on two populations of T cells, one adherent to cotton or nylon and the other nonadherent. The first population appeared to potentiate the latter. In contrast, the response to PHA was dependent only on the nonadherent T cell subpopulation. The responses to PHA and to Con A were both dependent on monocytes to approximately the same extent, but the response to Con A, unlike the response to PHA, was also slightly dependent on B cells.


Regulation of delayed-type hypersensitivity. II. Specific suppressor factor for delayed-type hypersensitivity to sheep erythrocytes in mice. An antigen-specific suppressor factor for delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) in mice is described. Lymph node cells and spleen cells from mice injected intravenously with 1 x 10(9) SRBC 4 days previously were incubated in vitro for 48 h in culture medium. Supernatant obtained from the culture inhibited the induction of DTH to SRBC in normal mice. It also suppressed the expression of DTH in presensitized mice. The suppression is specific as the suppressor factor had no effect on the DTH to noncross-reacting antigen, chicken red blood cells. Treatment of the spleen cells with anti-theta serum and complement prevented the production of the suppressor factor, whereas treatment with anti-Ig serum and complement had no effect. Suppressor factor produced by H-2k mice suppressed the DTH in H-2b mice. The factor thus seems to act across the H-2 barrier. The suppressor factor was not removed by adsorption with goat anti-mouse immunoglobulin immunoadsorbent, but could be adsorbed by SRBC. It was stable at 56 degrees C for 1 h, but was partially inactivated by freezing and thawing. The factor has a molecular weight of less than 35 000 daltons.


Regulation of delayed-type hypersensitivity. III. Effect of cyclophosphamide on the suppressor cells for delayed-type hypersensitivity to sheep erythrocytes in mice. A previous study (Eur. J. Immunol. 1977. 7: 714) has shown that mice injected intravenously (i.v.) with 4 x10(9) sheep red blood cells (SRBC) produce cells which suppress delayed-type hypersensitivity (DTH). These suppressor cells are theta-positive, antigen-specific and act via a soluble factor which does not bear immunoglobulin determinants (Eur. J. Immunol. 1978. 8: 168). The present paper demonstrates that these suppressor cells are inhibitable by cyclophosphamide (CY). Mice injected with graded amounts of CY two days prior to SRBC injection, showed maximum augmentation of DTH at 200 mg/kg body weight, a dose which completely suppressed the appearance of splenic plaque-forming cells (PFC) to SRBC. In contrast, lower doses of CY enhanced both DTH and PFC responses. Time course studies showed that CY inhibited the precursors of suppressor cells and had little or no effect on suppressor cells which have already encountered antigens. This was further confirmed by passive transfer studies which showed tha- suppressor cells were inhibited if CY was administered at the same time or 2 days before SRBC injection, but were not affected if CY was given after antigen stimulation. Direct evidence for the effect of CY on suppressor cells was obtained by cell fractination with a Ficoll density gradient. The denser suppressor cell population was absent from the spleens of mice treated with 200 mg/kg of CY 2 days before i.v. injection with 1 x 10(9) SRBC.


Tumor-induced changes in T cell mitogen responses in rats: suppression of spleen and blood lymphocyte responses and enhancement of thymocyte responses. Concanavalin A (Con A) and phytohemagglutinin (PHA) responses of spleen and blood lymphocytes from tumor-bearing (TB) rats were found to be markedly depressed in 4 different models employing tumors of spontaneous origin. Removal of phagocytic cells from both spleen and blood lymphocyte suspensions led to a complete restoration of the responses, indicating that the decreased responses were not due to intrinsic defects in the lymphocytes. The reduction was shown to be due to the inhibitory effect of an increase in the percentage of phagocytic cells. In addition, TB induced an atrophy of the thymus and a decrease in the number of thymic lymphocytes, mainly due to severe lymphocyte depletion in the cortex. The cells that remained in the thymus exhibited increased responsiveness to PHA and Con A as compared to thymus cells from normal rats. Similar results were found in hydrocortisone acetate-treated rats, suggesting that TB leads to a decrease in nonresponsive, cortical corticosteroid-sensitive thymocytes.


The spontaneous development of thymocytotoxic antibodies in athymic nude mice and its suppression after transfer of syngeneic thymocytes. Athymic nude mice early in life spontaneously develop a high level of thymocytotoxic antibodies which have characteristics similar to the thymocytotoxic autoantibodies occurring in young NZB mice. Thymocytotoxic activity was no longer detectable in the serum of nude mice two weeks after the intravenous injection of syngeneic thymocytes, although the levels of spontaneously occurring anti-DNA and anti-hapten antibodies were not affected by the cell transfer.


Enhancement of the action of colony stimulating factor (CSF) by soluble component(s) of erythrocytes in mouse bone marrow cells cultures. Rat erythrocytes, separated from other blood cells by SE-cellulose chromatography, were lysed by exposure to hypotonic solution, dialyzed and ultracentrifuged. The supernatant contained a substance which enhanced the activity of colony stimulating factor (CSF) in soft agar cultures of granulocyte-macrophage progenitor cells (CFU-C) from normal mouse bone marrow. The growth-enhancing effect of the erythrocyte factor was observed when mouse L-cell conditioned medium was used as the CSF source and also when serum from endotoxin-treated mice or from mice undergoing graft-versus-host reaction was used as the stimulant. The erythrocyte factor effect was also detected by 3H-thymidine uptake of bone marrow cells in liquid cultures. These results suggest that the effect of the erythrocyte factor on CSF is not restricted to CSF from a specific source nor to semi-solid agar cultures.


In vitro evidence for genetically determined variations in marrow erythroid cell sensitivity to chloramphenicol. The effect of chloramphenicol (CAP) was examined on the in vitro growth of CFU-E and CFU-C from four strains of mice: C57L/J, A/HEJ and their first generation hybrid LAF1, and the inbred strain C57BL/6J. The growth of marrow CFU-E from C57L/J and the hybrid LAF1 was inhibited by 82--96% at a CAP concentration of 10 microgram/ml compared to only 22--39% for CFU-E from A/HEJ and C57BL/6J. There was little difference in the degree of inhibition of CFU-C growth by CAP among the four strains, with that of C57L/J showing a slightly greater sensitivity to the drug. These results indicate a genetically-determined variation in the sensitivity of marrow erythroid cells to CAP.


Different colony stimulating activity by tumoral ascitic fluid and conditioned media. The effects of intraperitoneal Ehrlich ascites tumor (ET) growth on the kinetics of hemopoietic stem cells in the host bone marrow were studied using the spleen colony and the soft agar culture techniques. There is a decrease in spleen colony forming capacity of bone marrow of ET bearing mice, whereas in vitro assays of the committed macrophage granulocyte precursors, by the soft agar method, show that in the same circumstances a high yield of granulopoietic colonies can still be obtained. A shift of the CFU-c/CFU-s ratio from 15 to 36 thus occurs. Moreover, ascitic fluid from tumoral mice displays strong activity as CSF on normal mouse marrow, twice as strong as the standard mouse embryo CSF. When conditioned medium from cultures of ET cells (ET-CM) is tested, the pattern of agar colonies obtained is different from the previously obtained pattern of growth kinetics; furthermore many colonies are composed of undifferentiated cells. The hypothesis is suggested that among the variety of known CSF's, the ET-CM represents a unique factor, capable of inducing proliferation of marrow CFU-c, but only limited differentiation.


[alpha-Amylase activity in lysosomes of Aspergillus oryzae (author's transl)]. The alpha-amylase of mycelial cells of Aspergillus oryzae exists in a particular form in 8000 g pellet. The lysosomal localization of acid phosphatase is confirmed by electron microscopy. The purification of lysosomes by discontinuous gradient of sucrose in D2O shows that alpha-amylase activity is bound to these particles.


[Evidence of urinary glomerular basement membrane (GBM) antigens excretion in 3 rodents (rat, mouse, and guinea-pig) (author's transl)]. Immunodiffusion technique, with rabbits antibodies against rat glomerular basement membrane (GBM), permits to evidence the presence of GBM antigens into normal urines of 3 rodents (rat, mouse, and guinea-pig). These results confirm the earlier works in human and rabbit urines and show the antigenic communauty existing between the 3 rodents GBM, since we can evidence antigens of 3 different mammals with the same antibody. The origin and the nature of this patterns and the signification of this presence into mammalian urines are discussed.


The environment in which lymphocytes differentiate influences their ability to cooperate in vivo. Whether or not parental B lymphocytes cooperate with F1 T lymphocytes depends upon the environment in which parental bone marrow cells differentiate. Only those parental B lymphocytes that have differentiated in the F1 environment are able to cooperate with F1 T lymphocytes.


[Effect of 5-hydroxytryptophan and serotonin antagonists on the functional state of the adrenal cortex]. The effect of 5-oxytryptophan, injected singly and in combination with the serotonin antagonists (novocain, atropine and bigumal) on the ascorbic acid level in the adrenal cortex and the eosinophilic content in the peripheral blood of white rats was studied. It was ascertained that 5-oxytryptophan reduced significantly the amount of ascorbic acid in the adrenal cortex and produced eosinopenia. Novocain, atropine and bigumal did not exert a similar effect. A combined injection of 5-oxytryptophan together with the mentioned antagonists of serotonin prevented eosinopenia evoked by 5-oxytryptophan. At the same time, the tested antagonists of serotonin did not change the effect of 5-oxytryptophan on the level of ascorbic acid in the adrenal cortex.


Immune response and degree of protection in mice immunized with Trichomonas vaginalis antigen. The immune response and degree of protection of mice immunized with T. vaginalis sonicated antigen injected by intraperitoneal route, intraperitoneal and intravaginal only has been studied. Humoral response has been evaluated by indirect immunofluorescence and agglutination techniques; moreover, cytotoxicity of vaginal secreta has been investigated. Cellular response has been evaluated by stimulation of peripheral lymph-node cells and spleen lymphocytes with T. vaginalis antigen. It has been observed that inoculation by intraperitoneal plus intravaginal route induced a marked humoral and cellular response and a greater degree of protection.


Thorotrast induced adhesive arachnoiditis associated with meningioma and schwannoma. Adhesive arachnoiditis, a meningioma and a schwannoma were found at autopsy in a 56 year old man who had undergone Thorotrast myelography 33 years previously. Thorotrast was demonstrated in tissue sections by transmission and scanning electron microscopy, radioautography, and x-ray spectrometry.


Genetic variants of serum alpha-1-antitrypsin (Pi types) in Bretons. The results of Pi typing on 280 Bretons from Morbihan (Southern Brittany) are reported. 6 phenotypes and 5 alleles have been found in this study. Pi M is the most frequent as in other populations. Pi S and Pi F apears as the two main variants in population genetics.


Frequencies of different types of colour vision defects in the Netherlands. Two different population samples in Holland--one consisting of 1,093 boys from a technical school and the other of 493 male and 416 female students--were analysed for the presence of red-green colour vision defects. A total percentage of 7.3 for the male population was found. Based on the combined results of the Ishihara and HRR pseudoisochromatic plates, the Farnsworth 15-hue test and the anomaloscope, a subdivision of the deuteranomalous individuals into 3 subgroups is made. It is suggested that the differences between these groups may be genetic in nature and that the actual number of different genetic entities may still be greater.


In vitro studies on allotype suppression. IV. Abrogation of waning suppression by normal immunoglobulin of the suppressed allotype. The mechanism of allotype suppression in rabbits has been investigated by studying the in vitro immune responses of spleen cells from rabbits in advanced stages of spontaneous recovery from suppression. Whereas the spleen cells from highly suppressed rabbits can be released from their suppressed state only if treated with a combination of antibodies against the non-suppressed type and immunoglobulin (Ig) of the suppressed type, treatment with either of these two components alone suffices to overcome suppression when cells of more poorly suppressed spleen donors are used. The demonstration that suppression can be abrogated by normal Ig of the suppressed type alone, when cells are obtained from rabbits in the final phases of suppression, lends further support to the previously suggested concept that the probable role of this normal Ig in the release phenomenon may be that of neutralizing an effector of allotype-specific repression, possibly involving suppressor cells.


Cellular collaboration in the production of human leucocyte migration inhibition factor. The participation of cell subpopulations in the expression of leucocyte migration inhibition factor (LMIF) in response to Concanavalin A and Protein A was evaluated for cells isolated from the peripheral blood of five healthy subjects. LMIF activity could not be attributed to the function of T cells, B enriched cells, or monocytes acting alone, or to a combination of B enriched cells and monocytes. The LMIF response was the result of a collaborative event that occurred between T cells and B enriched cells, or between T cells and monocytes.


Plasmodium chabaudi in mice. Adoptive transfer of immunity with enriched populations of spleen T and B lymphocytes. Thymectomized NIH and C57BL mice were more susceptible to Plasmodium chabaudi than controls, indicating a role for T cells in acquired immunity to the parasite. Enriched populations of T and B cells were prepared from the spleens of immune mice using nylon-wool columns, and were adoptively transferred to syngeneic non-irradiated mice or mice irradiated with 600 or 800 rad. Some immunity could usually be transferred with immune T, B and glass-wool (g.w.) filtered spleen cell populations. In the heavily irradiated mice g.w. filtered immune spleen cells gave the best protection and the immune T cells the least. Preliminary attempts to show synergistic activity between immune T and B cells in irradiated mice were not successful.


The formation of B-lymphocyte colonies in agar contained in glass capillaries. Optimal conditions were established for a micro method for the production of colonies of B lymphocytes from mouse spleen cells cultured in agar in glass capillaries, in the presence of bacterial lipopolysaccharide (LPS). Besides LPS the cultures require 5 X 10(-5) M mercaptoethanol and 20% horse serum for optimal colony growth. Foetal calf serum and heat-inactivated horse or foetal calf serum were found to be inferior. An agar gel strength of 0.3% was best for colony counting. A sigmoid curve was obtained when the number of colonies formed was related to the seeded cell density suggesting that some kind of cell to cell co-operation is essential for colony formation. The daily kinetics of colony growth were followed by microscopic colony counting and photometric capillary scanning with integration of the signal areas. Both methods indicated that colony growth had ceased by day 6. The combination of both methods gave the most realistic picture of B-lymphocyte colony development.


Structure and biological function of human IgD. XVI. T and B lymphocytes in pityriasis rosea. The relative frequency of peripheral blood T and B cells and their biological function(s) from a group of patients with pityriasis rosea (PR) was investigated during the acute and convalescent phases of the disease using rosetting, immunofluorescent tests, and in vitro cell culturing with anti-delta and anti-mu antibodies and phytohemagglutinin (PHA). The total number of immunoglobulin (Ig) bearing cells was significantly increased, in conjunction with a slight decrease in the T cell population. Lymphocytes with surface IgD, IgM, or both Ig, accounted for the increase in the B cell population. This increase was transient, since it was only observed during the acute phase of the disease. In spite of the increase in IgD/IgM bearing B cells, the mitogenic responsiveness of B or T lymphocytes to anti-delta, anti-mu, or PHA was similar to the same patients during the convalescent phase, or to normal donors. Similarly, the levels of serum IgM, IgD, IgG, IgA and IgE in PR remained constant and at a normal concentration throughout the experimental period. The significance of the transient increase in IgD/IgM bearing cells in the pathogenesis and etiology of PR and its possible impact on the immune system is discussed.


T lymphocytes and anticardiac antibodies in patients with ischemic heart diseases. 85 patients with a variety of ischemic heart diseases were examined for the proportion of T cells and the presence of anticardiac antibodies. Patients with acute myocardial infarction during the 2nd and 3rd week of initial acute episode had a higher proportion of T lymphocytes and a higher proportion of patients developed anticardiac antibody. Similar was the case with patients with angina. The extent of infarction and accompanying complications did not change the immune parameters studied. The relationship of anticardiac antibodies and T lymphocytes in context of ischemic heart diseases is discussed.


Nomenclature for factors of the HLA system--1977. A Nomenclature Committee composed of geneticists and immunologists, including specialists in tissue typing, has met after each of the Histocompatibility Testing Workshops beginning with the 3rd Workshop in 1967. The Committee met again, in part under the auspices of the World Health Organisation and for report to the International Union of Immunological Societies, after the 7th Workshop in Oxford in September 1977, with the aim of updating the nomenclature for specificities of the HLA-A, B, C and D loci and establishing a nomenclature for the new specificities identified by serological techniques on B lymphocytes.


Evidence that nonspecific inhibitors are induced by soluble products of activated human lymphocytes. Cultures of lymphocytes stimulated by polyclonal mitogens or specific antigens exhibit an initial wave of cell proliferation followed by a decline which has been explained by the activation of suppressor T cells. This article presents the first results aiming at testing the possibility that the suppressor cells are activated by soluble products released by stimulated lymphocytes. It was found that the supernatants of PHA-activated human lymphocytes stimulate lymphocytes to DNA synthesis with peak responses occurring on day 5 independent of the cell concentration in the cultures. In contrast, the kinetics of lymphocyte responses to phytomitogens or in the mixed lymphocyte culture were found to be dependent on cell concentration; peak responses were delayed at decreasing cell concentrations. The results support the view that certain lymphokines released in stimulated lymphocyte cultures induce suppressor cells and that biologically active concentrations are reached earlier at high cell densities.


Unusual fungal infections associated with immunologic hyporeactivity. Two patients had unusual fungal infections, considered to be contaminants, which suggested immunologic hyporeactivity. One patient with a Fusarium infection had an associated occult malignancy. The other patient had an initial localized, then disseminated Curvularia infection. Both patients, following analysis of subpopulations of lymphocytes, showed evidence of relative T and B cell defects.


Final products obtained from the gamma radiolysis of frozen aqueous solutions of thymidine. The final radiation products obtained by gamma-irradiation of frozen aqueous solutions of thymidine have been identified as 5,6-dihydro-5,6-dihydroxythy-midine, 5,6-dihydrothymidine, thymidine dimers, 1-(2-deoxy-beta-D-threo-pento-furanosyl)-thymine, 1-(2-deoxy-alpha-L-threo-pentofuranosyl)-thymine, thymine and 5,6-dihydrothymine. The nature of the radiation products could be explained on the basis of the radical structures reported earlier.


Quantitative determination of cross-linkage of bacteriophage DNA and protein by ionizing radiation. Coliphage T7 was dissolved in tryptone broth and exposted to 60C gamma-radiation. Cross-linkage of DNA and protein of the virion was assayed using phenol-water countercurrent distribution. The results are interpreted in terms of a statistical model of cross-linkage and double-strand breaks. It was found that protein--DNA cross-links accumulate linearly with dose at a rate of o.74 X 10(-11) cross-links per rad per nucleotide pair, which is of the order of 5 per cent of the formation rate of double-strand breaks.


Radiolysis of chromatin extracted from cultured mammalian cells: production of alkali-labile strand damage in DNA. Chromatin has been isolated from cultured Chinese-hamster lung fibroblasts as an expanded aqueous gel. The DNA in isolated chromatin has been examined by sedimentation on alkaline sucrose gradients. The average molecular weight of the DNA has been determined to be 50 million. gamma-irradiation of isolated chromatin degrades the DNA to lower molecular weight. The yield of single-strand breaks in the DNA is 0.02 single-strand breaks per krad-10(6) dalton, calculated from a dose-range of &--400 krad and covering a DNA molecular weight range of 2 X 10(7)-1.4 X 10(5). There is a considerable difference in the efficiency of the formation of single-strand breaks in DNA irradiated as isolated chromatin compared with chromatin irradiated in whole cells before isolation. For isolated chromatin, values of 6 dV per break have been calculated compared with about 80 eV per break for chromatin irradiated in whole cells, which suggest a large contribution from indirect action by aqueous radicals in isolated chromatin.


Experimental studies of the translocation of plutonium from simulated wound sites in the rat. Wound contamination with plutonium was simulated in rats by injection into either muscle or subcutaneous tissue. The distribution after the injection of plutonium nitrate indicated that: (i) clearance from the contaminated tissue was due mainly to the movement of soluble complexes of plutonium, principally to the skeleton and liver, but also involved slower movement of polymerized, particulate plutonium to lymph nodes; (ii) clearance of soluble plutonium, and hence the overall state of clearance, was dependent on the tissue fluid flow through the contiminated tissue and the mass of plutonium deposited; (iii) lymphatic clearance of particulate plutonium resulted in the release of some particles into the circulation and subsequent uptake by the liver. Intramuscular deposition of small plutonium dioxide particles (approximately 1 nm in diameter) resulted in a greater rate of clearance of plutonium than deposition of the nitrate. Although the solubility of these particles was evident from the level of skeletal uptake of plutonium, a high level of excretion indicated that some plutonium was filtered into the urine in an undissolved form.