A calcium dependent inward current in frog skeletal muscle fibres.

Slow inward currents are here reported in frog skeletal muscle. The currents are turned on by depolarising the membrane beyond about -45mV and are blocked by replacement of Ca2+ by Mg2+ and in the presence of Ca2+ by Co2+ at 20mM.


Dual end-plate potentials at the single neuromuscular junction of the adult frog.

Electrophysiological evidence is presented that at least 30 percent of sartorius muscle fibres of adult frogs are innervated by two or more axons at a single end-plate zone. In these fibres, increasing stimulation of the common sartorius nerve led to the appearance of two or more distinct levels of end-plate potentials (e.p.p.) (or currents, measured by the voltage clamp technique). They had an identical time course, reversal potential and delay to nerve stimulation. When the recording microelectrode was moved along the same fibre and reinserted, both components of e.p.p. decreased proportionally. This indicated that both components of e.p.p. originated very closely to each other on the muscle fibre, presumably in one end-plate zone. Many fibres of the sartorius muscle of adult frogs therefore possess polyneural innervation of a single end-plate zone, which is otherwise typical for early stages of ontogenesis.


[Myocardial scintigraphy after injection of thallium 201 during exercise test. Results in 74 patients].

Thallium 201 is rapidly fixed by the healthy myocardium and its radiation detectable by a scintillation camera. It may be used to reveal and localise ischaemic zones after intravenous injection. In 74 patients undergoing an exercise test, the results of so-called effort scintigraphy were compared with effort electrocardiograms, coronary arteriography and scintigraphy after the injection of Thallium 201 at rest  (rest scintigraphy). The results of effort scintigraphy show a high degree of agreement with those of the effort electrocardiogram and of coronary arteriography. It would appear to be of great value in the determination of the permeability of aorto-coronary by-passes.


Proton magnetic resonance studies of 2'-,3'-, and 5'-deoxyadenosine conformations in solution.

Proton magnetic resonance studies of 2'-deoxyadenosine (2'-dA), 3'-deoxyadenosine (3'-dA), 5'-deoxyadenosine (5'-dA) and 8-bromo-5'-deoxyadenosine (8-Br-5'-dA) have been carried out in the temperature range between -60 degrees and +40 degrees C for ND3 solutios, +40 degrees and +100 degrees C for D2O solutions, and finally +10 degrees and +60 degrees C for pyridine solutions. The analysis is based on the two-state S in equilibrium N model of the ribose moiety proposed by Altona and Sundaralingam. In all solvents, 2'-dA favours slightly the S state of the ribose and the g+ conformer of the exocyclic CH2OH group. However, 3'-dA prefers strongly the N  state of the ribose and the g+ conformation. Both the S and N states of the ribose are equally favoured by 5'-DA and 8-Br-5'-dA. Evidence for the existence of an intramolecular hydrogen bond between 0(5') and N3 in purine (beta)-nucleosides is presented. It is also concluded that cordycepin (3'-dA) exists in solution mainly in the anti conformation of the base relative to the ribose.


Perhydrohistrionicotoxin: a potential ligand for the ion conductance modulator of the acetylcholine receptor.

Histrionicotoxin from the Colombian frog Dendrobates histrionicus and its perhydro derivative reversibly block the acetylcholine-sensitive ion conductance system in frog neuromuscular preparations. The perhydro derivative and [3H]perhydrohistrionicotoxin, like histrionicotoxin, caused a significant decrease in the peak amplitude of the end-plate current and shortened its rise time and half-decay time. In membrane preparations from Torpedo electroplax, [3H]perhydrohistrionicotoxin bound reversibly to a limited number of high-affinity sites [dissociation constant, (KD) = 0.4 micronM]. The ratio of perhydrohistrionicotoxin to acetylcholine binding sites in these membrane preparations approached 2. Histrionicotoxins, local anesthetics, and certain cholinergic agonists inhibited binding of perhydrohistrionicotoxin. Binding of perhydrohistrionicotoxin to membranes was decreased by heat or treatment with proteases. Treatment of membranes with Triton X-100 solubilized acetylcholine binding proteins and apparently also perhydrohistrionicotoxin-binding proteins. However, the detergent Triton X-100 also bound [3H]perhydrohistrionicotoxin. This nonspecific binding was not saturable and complicated studies on the antagonism by drugs of binding of [3H]perhydrohistrionicotoxin. In solubilized preparations the binding protein for acetylcholine could be removed by affinity chromatography or immunoprecipitation without affecting binding of perhydrohistrionicotoxin. Sephadex chromatography also separated acetylcholine- from perhydrohistrionicotoxin-binding proteins. Perhydrohistrionicotoxin did not bind significantly to purified acetylcholine-receptor protein but presumably bound to an ion conductance modulator protein that was associated with the acetylcholine-receptor in intact membrane and readily separable from the receptor protein after solubilization.


The base view in vertebral angiography. An aid in the diagnosis of extraaxial cerebellopontine angle tumors.

Though the advent of computed tomography has improved the detection of posterior fossa lesions, there are times when it can not be used to differentiate between an intra- and extraaxial lesion, particularly when the mass is anteriorly located. Base view angiography can be used to make this distinction, accurately localize the lesion, and demonstrate involvement or compression of vital adjoining structures.


Extrahepatic portal hypertension--long-term results.

This report reviews 164 cases derived from 2 Australian and 3 U.S. centres. There were 128 direct operations and 63 shunts. There were 16 deaths (10% mortality) but 3 were due to unrelated causes. Direct procedures; In the long term these appear of little value. 37 of 48 children having splenectomy subsequently rebled. Almost all children having ligation of varices and direct operations on the stomach rebled subsequently. Acute bleeding can almost always be controlled by conservative measures and direct operations would appear to offer no benefit over non-operative management except in the occasional case of catastrophic management that cannot be controlled conservatively. Shunts; A properly performed decompressive shunt offers the best hope of long term control for bleeding varices. Meso-caval shunts seem to give somewhat better results than splenorenal shunts. About two-thirds of the patients undergoing shunts remain free of any further bleeding. Non-operative management; 27 children have had no surgery performed and all are alive except for one child who subsequently died in a railroad accident. Bleeding episodes become less frequent after the age of 15 years and there are a number of reasons for this including the progressive development of natural shunts. We are not aware of any deaths or major complications from hypersplenism. Growth and development of all children in this series has been normal, although other have commented on a significant incidence of encephalopathy. Conclusions; 1. GIT bleeding becomes progressively less after the age of 15 years. 2. Direct operations have little place in treatment. 3. Decompressive shunts are the most effective method of controlling continuing bleeding but require a shunt of at least 1 cm diameter. 4. Splenomegaly and hypersplenism are not serious problems. 5. One can anticipate the progressive development of natural shunts. 6. Splenectomy should be avoided in this disease unless accompanied by a shunt.


[Multiple sclerosis in Tunisia. Clinical study of 100 cases].

One hundred cases of patients suffering from disseminated sclerosis (52 female and 48 male) were studied clinically and classified into four groups: typical, probable, possible and of acute onset. The present average age was 35.8 years and the age of onset of the disease 31.2 years. The mode of onset was progressive in 48 cases. The signs at onset were motor (44 p. 100), sensory (47 p. 100), ocular or visual (14 p. 100), vestibular (9 p. 100) and cerebellar (9 p. 100). An electronystagmogram was carried out in 74 cases: 44 were irritative in type, 22 deficitary and 8 normal. Electrophoresis of the cerebrospinal fluid revealed an increase in gamma globulins in 47 out of the 62 cases examined. Study of the geographic distribution of the place of birth and residence of the patients showed only a predominance in the northern part of Tunisia, probably related to easier communication from these regions with the Neurology Centre in Tunis.


Communicating with the rheumatic patient.

To explore the meanings attached to words by patients and doctors, a multiple-choice questionnaire was given to 214 rheumatic patients, 110 non-rheumatic patients, 227 rheumatologists and 36 general practitioners. Words and phrases dealt with symptoms in descriptive terms, common disorders and parts of the body relevant to rheumatology. Poor agreement was obtained for 'back' among rheumatologists and hospital doctors, and for 'arthritis' among general practitioners. The word 'sciatica' means very different things to different doctors. Among rheumatic sufferers good agreement was only reached for 'rheumatism' and 'hereditary'. Non-rheumatic sufferers obtained better agreement than the rheumatic patients. This may have been due to more in the professional classes among the former group. The poorest agreement among rheumatic patients was for 'numbness', 'sciatica', 'slipped disc', 'vertebra', 'cervical', 'spinal cord', 'arthritis', 'deformity', 'anaemia', 'ligaments', 'osteoarthritis', 'lumbar', 'sacrum' and 'back'. Poor doctor-patient correlation between patients and rheumatologists occurred for 'numbness', 'spinal cord', 'cervical', 'sacrum', 'loin', 'slipped disc', 'arthritis', 'osteoarthritis' and 'steroids'.


[Knee arthroplasty. Our experiences with 22 cases].

In spite of continuing progress, total knee arthroplasty still presents many problems. In this clinic 25 arthroplasties have been performed in 22 patients over the last 4 1/2 years. Guépar hinges were used in 21 knees and Marmor modular knees in 4. Acrylic cement was used in all cases. The mean age of the patients was 69 years. 13 had osteoarthritis, 5 rheumatoid disease and 4 other conditions. There were no serious general complications or infections in the early postoperative period. The commonest local complication was malalignment of the patella (17 cases); 2 of these were complete but reducible dislocations. In only 3 knees did patellar subluxation produce sufficient pain to spoil an otherwise good result. Prostheses have loosened in 2 knees, one of which has been fused with success. Striking features of the early results have been reliable pain relief, improvement of joint movement, and generally an increased walking capacity. In spite of its present problems, arthroplasty remains the procedure of choice in knees where the amount of articular damage contraindicates conservative surgery.


Recurrent spontaneous pneumothoraces associated with pulmonary histiocytosis X. A case report.

A 20-year-old Coloured woman presented on three occasions with recurrent right-sided spontaneous pneumothorax which proved to be associated with pulmonary histiocytosis X. After corticosteroid therapy there was no recurrence of pneumothorax or radiographic evidence of progressive disease during a 6-month follow-up period.


Simultaneous prevention of blood abnormalities and hereditary congenital amputations in a brachydactylous rabbit stock.

Hematological and histological studies of the rabbit brachydactyly mutant were made to clarify the question of the blood abnormality that had previously been implicated in the teratogenic process leading to congenital amputation. The hemoglobin of fetal and adult br/br rabbits, studied by electrophoresis and cyanmethemoglobin assay, exhibited no differences from that of controls. The br/br fetuses were polycythemic and severely macrocytic. Fetal limb vessels showed thrombosis leading to hemorrhages in the extremities. The hepatic tissue was abnormal, being particularly poor in hematopoietic cells; blood cell macrocytosis was attributed to impaired erthropoiesis. Treatment of pregnant rabbits with folic acid plus vitamin B12 or with folinic acid was able simultaneously to prevent the fetal blood cell macrocytosis and the congenital abnormalities.


[Complications after ambulatory oral surgical interventions, their frequency and importance].

The rate of complications of the healing process observed during or after oral surgical intervention on an outpatient basis amounts to 9.75% of the cases. Most frequently occur tooth-root fractures, alveolitis/osteitis, osteomyelitis, soft-tissue infections, haematomas, postoperative bleedings, antral perforations, sinusitis and perception disorders. The great medical and economic importance of such complications is pointed to on the basis of personal results and relevant data from the literature. An improvement in treatment results can be aimed at by reducing the rate of complications as well as by shortening the duration of treatment. Some relevant suggestions are given.


Biologic activities of various thymus preparations.

Thymosin and THF were prepared from total normal calf thymus (TT), from calf thymus depleted of thymocytes by whole-body irradiation (TE), and from calf thymus lymphocytes (TL). The activities of these products were compared in four different in vitro assays that monitored for various T-cell functions. The results suggest that the preparations obtained from thymus epithelium are more active in inducing T helper cell function in nude/nude mouse spleen cells than substances isolated from thymus lymphocytes. The latter seem to act on a more advanced step in the T cell line differentiation.


Fate of experimental allogeneically transplanted fetal adrenal glands in nonimmunosuppressed adrenalectomized adult rats.

Long-term survival of allogeneic vascularized fetal adrenal transplants has been demonstrated in adrenalectomized rats. Significant less mortality occurred after adrenalectomy in animals receiving multiple allogeneic fetal transplants compared to nontransplanted rats.


Differential tuberculin test for mycobacterial infection in children.

A composite antigen prepared from strains of M. avium, M. intracellulare and M. scrofulaceum has been used in addition to PPD in differential skin tests, principally on children investigated for mycobacterial cervical adenitis. The tests were uniformly successful in 12 cases bacteriologically positive for opportunist mycobacteria and gave unequivocal positive or negative results in 30 cases awaiting diagnosis.


[Informational activity of exogenous DNA in irradiated cells].

The levels of total DNA, RNA and protein synthesis were examined in control and in vivo irradiated thymocytes after their preincubation with exogenous DNA of different polymerization degree. The studies were made using the uridine-14C and lysine-14C. The influence of preliminary treatment of exogenous DNA or cells with actinomycin D (AMD) was studied as applied to the levels of their own and "induced" synthesis in the cells. It is shown that native exogenous DNA induced the increase in the synthesis of all three components only in the irradiated cells. The pretreatment of the irradiated cells or exogenous DNA with AMD completely inhibits the "induced" synthesis of RNA and protein while their own synthesis in suppressed only by 20%. Possible transcription and translation of highly polymerized exogenous DNA in the irradiated cells without its integration into the genome of the "host" is discussed.


[Passive transfer of tuberculin sensitivity (author's transl)].

Tuberculin sensitivity can be transfered passively by cells. The active principle may be bound on T-lymphocytes. In patients with sarcoidosis or with malignant lymphadenomas, the passive transfer of tuberculin sensitivity via lymphocytes of tuberculin-positive donors is more difficult. In sarcoidosis the achievement of a positive tuberculin reaction at an appreciable distance from the site of transfer was possible only with markedly greater amounts of donor lymphocytes than in healthy controls. In patients with malignant lymphadenomas such a transfer succeeded only very rarely. The qualitative and quantitative differences in the impairment of the delayed immune sensitivity in both groups and their possible causes are discussed.


[Special diagnostic and therapeutic aspects of pulmonary histiocytosis X in twelve cases from 1969 to 1975 (author's transl)].

15 cases of histiocytosis X and 274 cases of histologically confirmed sarcoidosis were diagnosed during the investigation period from 1969 to 1975. Data of 12 adults with primary pulmonary histiocytosis X were evaluated in extenso. The necessary histological verification of diagnosis was only possible by open lung biopsy. Already in early stage small excavations were found by tomography in half of the cases. Eelvation of serum copper and of the index of leukocyte alkaline phosphatase was striking. In a single  case antinuclear antibodies were proven. An intra patient comparison verifies corticosteroids suppressing the disease. On the occasion of a second lung biopsy in one case could be seen that after treatment no more histiocytosis-specific substrate was existing. Exacerbation and relapse during and after continuous long-term therapy were not observed. The features of histiocytosis X and sarcoidosis are set side by side in order to show differences and relations.


Failure of correlation between in vitro and in vivo effect of T and B cell mitogens in the mouse.

T and B cell mitogens as PHA, PWM, LPS, SIII, DS, PVP were investigated in vitro in direct MI assay with mouse PECs as well as in vivo for their phagocytosis-enhancing capacity. All mitogens induced a dose-dependent MI although of differing degrees. In contrast, a phagocytosis-stimulating effect in vivo could be observed only by using the mitogens of bacterial origin such as LPS and SIII; the other mitogens induced, however, rather a loss of phagocytosis, although a cellular reaction in the sense of an increased PEC number was partly registered. The reactivity of PEC to LPS but not to PHA disappeared in the MI assay after foregoing desensitization of mice with the corresponding mitogen, suggesting the existence of a cellular immunity against the bacterial antigen. The importance of the induction of cell-mediated events in infection immunity in a classical immunological way will be discussed.


[New methods of managing massive upper gastrointestinal bleedings (author's transl)].

A four year experience in the management of 585 patients with massive upper gastrointestinal tract bleeding (U. G. I. B.)has been reviewed. The effect of routine fiberoptic gastroscopy, selective angiography, and selective pitressin arterial infusion has been analyzed as it effects the more accurate diagnosis and better non-operative therapy of these dangerously ill patients. Duodenal and gastric ulcer, which comprise one-half of such patients, are best treated by early operation. Mallory-Weiss-syndrome is more frequent than previously appreciated. Pitressin infusion is worthy of trial in diffuse gastritis, varicose- and stress ulcer bleeding. Stress bleeding is usually one manifestation of multiple organ failure due to bacterial sepsis.


[Examinations of upper gastrointestinal bleeding - value of emergency endoscopy (author's transl)].

The treatment of the acute upper gastrointestinal bleeding can be improved by using standardized immediate actions, as there is endoscopy in emergency diagnostics. Endoscopy gives much higher certainty in pre-operative diagnostic, better possibility of planning and more exact timing of the operation. Therefore emergency endoscopy should be done in any case of acute upper gastro-intestinal bleeding.


[Results of surgical treatment of peptic ulcer in old age (author's transl)].

The poor results of surgical treatment of peptic ulceration in old age can only be improved if both internal medicine and surgery will find guiding principles for operative indications. 1. Chronic ulcer is an indication of operative treatment even in old age. - 2. Conservative treatment of phyloric stenosis caused by peptic ulceration is only permissable, if a florid ulcer in evident. - 3. The evidence of a chronic bleeding ulcer indicates surgical treatment. Suitable short-time conservative treatment gives better conditions for any type of surgery.-4. The perforated ulcer in old age should only be treated by the smallest surgical procedure. Antibiotic therapy should begin immediately after establishing the diagnosis.


[Periods of formation of the mechanisms of "reward" and "punishment" in rats during postnatal ontogenesis].

The manifestation of some signs of emotional reactions produced by stimulation of the hypothalamic zones through implanted electrodes was studied in chronic experiments on 8- to 40-day old rats. Beginning with the 12th day of the rats' development, the formation of the instrumental reaction of self-stimulation and avoidance was studied. It has been found that maturation of the negative emotion mechanism preceds that of the positive emotion mechanism. Proceeding from the results obtained, a hypothesis has been advanced on heterochronous maturation of the systems of positive and negative reinforcements. It has been assumed that beginning with certain stage of the animals' development, behaviour is being controlled with the participation of a non-specific "reward" mechanism.


[Catecholamine excretion as an index of the effectiveness of treatment in radiculitis patients with a pain syndrome].

The authors studied the excretion of catecholamines in the diurnal urine in patients with sacrolumbar and cervicothoracal radiculitis in the acute stage with pain and the changes of excretion under the influence of physiotherapy. In radiculities with the pain syndrome there was an activation of catecholamine systems, mainly in the hormonial link of the sympathico-adrenal system. Following treatment along with the disappearance of the pain syndrome there is a normalization of the excretion of adrenalin, noradrenalin and the terminal product of inactivated catecholamine in the diurnal urine. This gives ground to assume that the results of these biochemical studies may serve as indices of the therapeutic effectiveness.


Causes of enucleation following cataract surgery.

Between the years 1962 and 1976 85 eyes which had undergone cataract surgery were accessioned to the Ophthalmic Pathology Laboratory of the Helsinki University Eye Hospital. The specimens were submitted from the various eye departments of the country. Of these 8k eyes nine had been enucleated within 2 months after surgery while in 64 cases the enucleation had been performed more than 12 months after surgery. 40 eyes had had an attempted operation for senile cataract, 30 eyes for traumatic cataract while the remaining cases were congenital cataract cases or cataracts in pre-existing glaucomatous or chronic uveitis eyes. Most frequent causes for the loss of the eyes were related to incomplete or abnormal healing of the operative wound such as epithelial down-growth and closure of the chamber angle with extensive anterior synechiae leading to absolute glaucoma. It is noteworthy that all cases of epithelial downgrowth were derived from the beginning of the observation period. No new cases were obtained after 1969. Other important causes were purulent endophthalmitis and retinal detachment. Haemosiderosis was a prominent cause in the group with traumatic cataract. A careful histopathological analysis of eyes enucleated after cataract surgery is mandatory as it is from the complications we learn most in cataract surgery.


Factor XIII (fibrin stabilising factor) in Henoch-Schönlein's purpura.

In 13 out of 17 consecutive children with Henoch-Schönlein's purpura the factor XIII determined with the dansyl cadaverine method was found to be decreased during the acute phase. The decrease is assumed to be due to a specific degradation by proteolytic enzymes liberated from inflammatory cells, with defective local haemostasis as a result. This assumption is strengthened by the observation that treatment with factor XIII combined with an antifibrinolytic drug controlled life-threatening gastro-intestinal bleeding in one of the patients. It would therefore appear that such treatment might offer a new possibility of controlling severe haemorrhages in Henoch-Schönlein's purpura.


[Mitochondrial membrane proteins of lower vertebrates].

Mitochondria from the liver, heart and skeletal muscles of lower vertebrates were studied with the method of IR-spectrometry in the spectral region of amide I and amide II bands. The kinetics of H--D exhange of peptide protons was measured with the same method before and after low-temperature gradual extraction of lipids. It was revealed that mitochondria of different tissues taken from several species of lower vertebrates have a similar stable configuration of amide I band and similar kinetics of H--D exhange in peptide groups of proteins (35--40% of labile peptide protons and 40--50% of stable ones). This suggests that mitochondrial proteins have a similar conformation in membranes. In the first hour of gradual low-temperature extraction of phospholipids from liver mitochondria of the frog (chloroform-methanol, 5 : 1), the increase in labile protons content and the decrease in stable ones could be detected in mitochondrial proteins. During the next 5 hours of extraction, the quantity of labile peptide protons and the content of phospholipids in the extract remained unchanged. Low-temperature extraction of heart mitochondria of the frog Rana temporaria with less polar solutions (chloroform-methanol, 30 : 1 or 20 : 1) gave no rise in the content of labile peptide protons in spite of the large amounts of extracted phospholipids.. These data indicate that tissue specificity of mitochondria is based primarily on the phospholipid component of membranes. The regulatory mechanisms which stabilize the optimal conformation of membrane proteins are different in liver and heart mitochondria.


Chemotherapy of metastatic carcinoma of the breast. A 4-drug regimen.

Combination chemotherapy (vincristine, adriamycin, cyclophosphamide, methotrexate with leucoverin rescue) in 32 patients with metastatic carcinoma of the breast resulted in an overall response rate of 81 per cent (9/32 complete remission, 17/32 partial remission). No serious side effects were noted. Karnofsky performance index improved in 24/26 responders.


Reduced incidence of intraoperative myocardial infarction during coronary bypass surgery with use of intracoronary shunt technique.

Intraoperative myocardial infarction is a recognized complication of aortocoronary bypass surgery. One major cause of such infarction may be interruption of coronary blood flow, particularly in patient with poor coronary collateral circulation. In 30 patients use of an intracoronary shunt made it possible to limit the period of coronary occulusion during graft construction to a few minutes. Use of this shunt was associated with a reduced incidence of intraoperative myocardial infarction (as judged by the appearance of new Q waves) when these patients were compared with 50 patients operated on without this procedure (6 of 50 [12 percent] versus 0 of 30). The incidence of postoperative persistent S-T segment elevation was reduced from 21 of 50 (42 percent) to 5 of 30 (17 percent). Except for use of the shunt, the surgical technique was identical in the two groups of patients.


Improved survival after coronary bypass surgery in patients with poor left ventricular function: role of intraaortic balloon counterpulsation.

The operative mortality rate of aortocoronary bypass surgery in 23 patients with poor left ventricular function (ejection fraction 0.30 or less) operated on in 1973-74 was 34.7 percent. The incidence rate of operative myocardial infarction was 30.4 percent. In an attempt to improve survival, intraaortic balloon counterpulsation was used therafter in 25 similar patients. Counterpulsation was instituted preoperatively and continued intra- and postoperatively for 2 to 5 days. Preoperative studies revealed an "unloading" effect of the left ventricle, with significant reductions of systolic arterial blood pressure, end-diastolic pulmonary arterial pressure and end-diastolic left ventricular volume and pressure. Metabolic improvement was demonstrated by the lesser production of myocardial lactate after pacing-induced tachycardia when the ventricle was balloon-assisted. Intraoperatively, blood flow through the vein graft was found to increase with counterpulsation. The rate of operative myocardial infarction was reduced to 4 percent and the mortality rate to 8 percent. In patients who have sustained a significant loss of functioning myocardium, the beneficial hemodynamic and metabolic effects of intraaortic balloon counterpulsation appear to prevent furhter, possibly critical, myocardial damage in the perioperative period.


Postextrasystolic potentiation as a predictor of potential myocardial viability: preoperative analyses compared with studies after coronary bypass surgery.

The ability to predict reversibility of ventricular dysfunction should be important in determining operability. This study examined the usefulness of postextrasystolic potentiation as such a predictor. Left ventricular wall motion was studied using cineventriculography in 31 patients before and after revascularization surgery. Preoperative ejection fraction and wall motion were analyzed during a sinus beat and after a random ventricular extrasystole, whereas postoperative ejection fraction and wall motion were examined only during a sinus beat. Changes in ventricular motion were correlated with changes in vascular supply achieved by operation. Of the 7 patients whose ejection fraction was improved postoperatively, 6 had shown postextrasystolic potentiation compared with only 10 of the 24 patients without such improvement (P less than 0.05). Regional wall motion analysis also showed a significant association between postextrasystolic potentiation and postoperative improvement in wall motion. Of 26 zones judged to have an increased vascular supply after operation, 11 showed increased motion postoperatively. All 11 had shown postextrasystolic potentiation, compared with only 5 of 15 zones with increased vascular supply but without increased postoperative motion (P less than 0.001). Thus, postextrasystolic potentiation seems to be a useful predictor of the ability of asynergic myocardium to respond to successful revascularization surgery.


Diagnosis of a bleeding Meckel's diverticulum using radiopertechnetate.

A case report of bleeding from a Meckel's diverticulum diagnosed by Tc99-m pertechnetate scanning is presented. The noninvasive advantage of this method justifies its early use as a diagnostic measure when a Meckel's diverticulum is suspected in the differential diagnosis of lower gastrointestinal bleeding.


Molecular abnormality of PI S variant of human alpha1-antitrypsin.

Alpha1-antitrypsin variant protein was purified to homogeneity from a PI S-S subject with a mild deficiency of plasma trypsin inhibiting capacity. Molecular weight, specific trypsin inhibitory activity, and composition of amino acids and carbohydrates were similar to the proteins purified from Pi M-M individuals with normal alpha1-antitrypsin activity. The structural difference between the normal and the variant alpha1-antitrypsin was elucidated by peptide mapping of their tryptic digests. An amino acid substitution of glutamic acid in the normal protein to valine in the variant protein was found. The result is consistent with the previously reported amino acid substitution in Pi S-Christchurch.


Posterior amorphous corneal dystrophy.

A family of ten individuals aged 18 months to 75 years had biomicroscopic findings consisting of large, amorphous, sheet-like opacifications of the posterior stroma and Descemet's membrane, and alterations of the endothelium. A uniform thinning of the cornea was present. These findings do not conform to previously described corneal dystrophies. The condition appears minimally progressive and the three-generation pedigree indicated an autosomal-dominant inheritance pattern.


Meesmann's epithelial dystrophy of the cornea.

Two separate pedigrees had typical Meesmann's dystrophy of the corneal epithelium. Histologic examination of one patient from each pedigree showed two characteristic findings in corneal epithelium; the previously designated "peculiar substance" in the cells, and the vacuolated homogeneous substance mostly within the cysts. The primary disturbance probably involves the cytoplasmic ground substance that ultimately may result in complete homogenization of cells and the formation of cysts. Thickening of the epithelial basement membrane is variable and is a nonspecific response by the epithelial basal cells.


Arteriovenous malformations of the colon.

Arteriovenous malformations have become recognized as a major cause of massive bleeding of the colonic origin. Although an arteriographic unit capable of serial magnification is ideal for detecting arteriovenous malformations in the bowel, the diagnosis may still be made by a combined approach of conventional arteriography, colonoscopy and operative juddment. the final diagnosis rests on gross and histologic demostration of vascular malformations in the excised specimen.


Fiberoptic intraoperative illumination of the stomach as an aid in the management of acute gastric hemorrhage.

Intragastric illumination using a flexible light source is described as a technical aid in the management of gastric bleeding. The flexible light source can be recommended for illumination of the proximal intragastric area to facilitate surgical control of bleeding from Mallory-Weiss lacerations, ulcers, varices, and mucosal erosions. The sterile sheath-covered flexible neck of the light allows exact positioning of the light in the surgical field by the operating surgeon.


Compensatory responses in the development of the brachial lateral motor column in triploid Rana pipiens.

Responses of the lateral motor column (LMC) in the frog spinal cord to various experimental manipulations generally are manifested in an adjustment of the number and sizes of the motor neurons. Analysis of the brachial LMC in induced-triploid Rana pipiens larvae as compared to diploid controls revealed a significant increase in nuclear size with a concomitant reduction in cell counts at all stages of development examined. These compensatory responses of the LMC to polyploidy in normal size frog larvae are consistent with results reported for other amphibian polyploid tissues and serve as a basis for exploring mechanisms of plasticity in the developing central nervous system.


Atypical progressive angina pectoris caused by a congenital coronary-pulmonary shunt and coronary atherosclerosis.

A 57-year-old man with atypical progressive angina caused by congenital coronary-pulmonary shunt and coronary atherosclerosis is described. The angina was rather consistently unresponsive to nitroglycerin. Following closure of the shunt and aortocoronary bypass surgery, the patient became asymptomatic and has remained free of angina 2 year postoperatively. Although the congenital anomaly is rare in adults, it may be considered in the differential diagnosis of atypical angina pectoris, particularly when there is either continuous murmur or systolic murmur over the lower parasternal area.


Is coronary artery bypass in the community hospital justifiable?

Coronary artery bypass can be performed at the community hospital level with results comparable to those in major university centers. Four hundred and ninety-seven patients were operated on between 1970 and 1976 with an overall early mortality of 4.4% (2.6% for coronary artery bypass only) and improvement in the quality of life in 88% of patients.


[Trypsic inhibitors in serum and hyaline membrane disease (author's transl)].

Alpha1 antitrypsin (A1AT), alpha2 macroglobulin, alpha, quimotrypsin, interalpha1 antitrypsin and trypsin inhibitory capacity in serum of newborn with hyaline membrane disease, are compared with values obtained in other dis orders, and with normal newborn at different gestacional age. Significant decreased level of A1AT and trypsin inhibitory capacity were found in hyaline membrane patients, that were in order to symptoms severity and time in which samples were obtained. A1AT immunofluorescent study of hyaline membrane in died newborns was positive allowing to explain the low levels found in serum. Presence of fibrine IgG, C1a and C3 in hyaline membrane is according to it's composition by plasmatic components. Thus a new pathogenic mecanisme (derived of the plasma viscosity in the alveolar layer) could be present in hyaline membrane formation.


[Hypochondroplasia: an effected family presentation (author's transl)].

A family suffering from hypochondroplasia in which father, mother and offspring are affected and in whose family tree various probably affected members are found on both sides, according to a pattern of autosomic dominant heritage is presented. The difficulty of diagnosis is discussed, not only in the first years of life but also later on, and in mild or moderate forms, which may in part explain the  few cases reported in the literature.


Alpha1-antitrypsin deficiency with severe panniculitis. Report of two cases.

Two patients with profound decrease of alpha1-antitrypsin (PiZZ) presented with severe pannicultis (Weber-Christian disease); one had systemic panniculitis including pancreatitis. Another possible case is quoted from the literature. Although milder forms of panniculitis can have normal Pi phenotypes and alpha1-antitrypsin levels, the marked reduction of antiproteolytic activity found in PiZZ homozygotes may predispose to or aggravate the lesions of Weber-Christian disease.


Histopathology of Goldmann-Favre syndrome obtained by full-thickness eye-wall biopsy.

The first histopathologic specimen form the eye of a patient with Goldmann-Favre syndrome was obtained by full-thickness eye-wall biopsy. Diagnosis was established by an early history of night blindness, characteristic clinical features including atypical pigmentary retinopathy, peripheral retinoschisis, opaque "sclerotic-appearing" peripheral retinal vessels, vitreous changes including liquefaction and condensed vitreous bands and a non-detectable electroretinogram (ERG). Histopathologic changes from a 4 mm peripheral area included diffuse degenerative changes involving predominantly the sensory retinal layers with a relatively normal pigment epithelium and choroid. Vascular changes included thickened retinal vessel basement membranes and areas of vascular occlusion. These findings are compatible with a primary photoreceptor involvement in addition to a vascular component. A thick preretinal membrane of glial tissue was an additional finding.


Growth charts, "curative" or "preventive"?

The type of growth chart now bcoming widely used in developing countries is described; its objectives differ from those of the charts used by paediatricians in industrialized countries. Alternative weight standards to the Harvard have been suggested by a WHO Working Party and adopted for the chart described here. The--3 and --4 standard deviations from these standards are also available printed on plastic overlays.


Polybrene neutralization as a means of monitoring heparin therapy for extracoporeal cirulation.

Dose-response effects of heparin and protamine in 34 adult patients undergoing cardiac operations were monitored by an in vitro analysis utilizing hexadimetharine bromide (Polybrene) neutralization. Heparin administered prior to cannulation for cardiopulmonary bypass in a dose of 3.0 mg (300 units) per kilogram of body weight, and 1.5 mg (150 units) per kilogram for each subsequent hour of bypass, routinely produced circulating heparin concentrations greater than 1.0 units per milliliter of plasma. A protamine dose equal to 80% of the total number of milligrams of heparin given resulted in no detectable plasma heparin in 23 of the 34 patients one-half hour after administration. No patient required protamine in an amount greater than the total number of milligrams in the heparin dose to achieve heparin neutralization. Modest postoperative chest tube drainage (mean, 784 ml in 48 hours) in these patients provides clinical support for low-dose protamine administration for heparin neutralization at the conclusion of cardiopulmonary bypass.


Antigenic competition between two sequentially acting antigens. II.--The life-span and sensitivity to corticosteroids or to irradiation of T suppressor cells.

We have studied the immunosuppressive function of T cells using the antigenic competition system. A first antigen (inhibitory antigen) consisting of horse red blood cells is given as a primary or a secondary stimulus. This is followed 4 days later by a second antigen (test antigen) consisting of sheep red blood cells. Both antigens are given intraperitonealy. We have estimated the life-span of T suppressor cells by studying the time necessary for the abolition of antigenic competition after adult thymectomy. We find the response disappears after 6 weeks. The cortico- and radio-sensitivity of T suppressor cells were studied by the effect of hydrocortisone or of irradiation on antigenic competition. Lymphocytes from treated mice were transferred to compatible Nude mice whose ability to show antigenic competition was then studied. By these tichniques we have shown that T suppressor cells are not destroyed by hydrocortisone but their immunosuppressive function is merely temporarily inhibited during the time of high level of this hormone. Furthermore hydrocortisone only inhibits the T suppressor cells when the inhibitory antigen is given as a primary stimulus and shortly after the administration of the steroid. Irradiation on the other hand destroys or inactivates one out two or both cells with a suppressive activity (T suppressor cell and macrophage).


Linkage between an X-chromosome marker (deutan color blindness) and bipolar affective illness. Occurrence in the family of a lithium carbonate-responsive schizo-affective proband.

Studies with X-chromosome markers in mental illness have been limited to the diagnostic concept of primary affective disorders. The present study is the first to our knowledge to demonstrate statistically measurable linkage between color blindness and manic-depressive illness in a family identified by a schizo-affective proband. Linkage data and lithium carbonate response in the proband suggest that the schizophreniform-affective spectrum in members of the pedigree may reflect a genetically distinct disorder. The use of a genetic marker as a heuristic diagnostic criterion in a subgroup of heredofamilial psychoses with unclear diagnostic boundaries is proposed.


Affinity chromatographic analysis of murine interferons induced by viruses and by T and B cell stimulants.

Murine interferons induced by viruses and by non-viral substances such as lectins, tilorone, lipopolysaccharide and Brucella have been analysed by affinity chromatography on a column of Sepharose coupled to antiviral interferon antibodies. The results reported here suggest that virus and B-cell stimulants induced interferons which are antigenically related and that T cell-dependent mitogens induce and "interferon like" molecule which appears to be antigenically and physiocochemically different.


Acute posterior multifocal placoid pigment epitheliopathy and thyroiditis.

A young woman developed the characteristic clinical and fluorescein angiographic findings of acute posterior multifocal placoid retinal pigment epitheliopathy while being treated for acute thyroiditis. Widespread involvement of the cornea, uveal tract, as well as the optic nerve and retina indicate a generalized ocular inflammation in the clinical course of this patient. The relationship between the subacute thyroiditis and acute posterior multifocal placoid retinal pigment epitheliopathy may indicate an underlying viral cause of both disorders.


[Postcommotional syndrome in electronystagmogram of penduling test (author's transl)].

31% of the 270 patients who consulted the ORL-specialist because of vertigo after commotio cerebri had a central nystagmus pattern (écriture centrale) during the penduling test. This is the expression of the vestibular center to an irritation of the brain stem after commotio. In many of these cases the EEG was normal.


Spontaneous and positional nystagmus in healthy persons demonstrated only by electronystagmography: physiological spontaneous nystagmus or "functional scar"?

We wanted to ascertain whether a physiological horizontal vestibular spontaneous nystagmus is existent, or whether the spontaneous and positional nystagmus seen in clinically healthy persons in the electronystagmogram -- when fixation had been excluded completely -- was always the result of earlier damages to the vestibular system (Jatho). For this purpose we tried to detect a spontaneous and positional nystagmus in 102 healthy persons from 6 age groups (17 each) between 11 and 70 years of age. When the ENG was registered with open eyes in darkness, 63 out of the 102 test persons had a horizontal spontaneous or positional nystagmus, however, under the Frenzel glasses there was a nystagmus in only 2 out of these test persons. With open eyes in darkness, the frequency and intensity was the same in all age groups. With this, we believe to have proved that a physiological horizontal vestibular nystagmus does exist. We share Kornhuber's opinion that the examination with the Frenzel glasses in a dark room, together with the head shaking test and positional test, at the present time represents the best method for differentiating between physiological and pathological spontaneous nystagmus.


Synaptogenesis of the efferent vestibular nerve endings of the cat: ultrastructural study.

The maturation of the innervation of the sensory hair cells of the cristae ampullares was studied in the newborn cat. The essential characteristics of the adult are already present in the type II cells at this age. The type I cells on the contrary reveal different degrees of maturation. It was observed that in the immature stages the efferent endings which were already filled with synaptic vesicles were in direct contact with the membrane of the sensory cell. The nerve chalice as it settles into place breaks this contact and simultaneously a synapse is created between the efferent endings and the afferent chalice.


A point prevalence study of outpatients and inpatients in the mental health services, general hospital psychiatric units, and under private psychiatrists in Perth, Western Australia.

A one day point prevalence study of all inpatients and a one week point prevalence study of all out-patients, seen by psychiatrists in Perth, Western Australia, was conducted. On the census day in July 1971, 61 per cent of all psychiatric inpatients in Perth were long-stay patients. Of the short-stay patients 75 per cent were in Mental Health Services hospitals, 17 per cent were in general hospital psychiatric units and 8 per cent were under private psychiatrists. The bed occupancy rate was 129.7 per 100,000 population for the whole State--83.2 long-stay and 46.5 short-stay. These rates were low compared with published figures in other countries. The proportions of total outpatients seen during the census week by the Mental Health Services, general hospital units and private psychiatrists were 53.5 per cent, 16.0 per cent and 30.5 per cent respectively. There was a differential use of psychiatric services between immigrants and Australian-born outpatients.


Clinical medicine review: three unique presentations of ischemic heart disease.

Unstable angina pectoris, Prinzmetal variant angina, and ischemic heart disease with normal coronary arteries, are three unique syndromes of ischemic heart disease that have recently become better understood. With the recognition of their manifestations, the combination of modern medical techniques and collaborative epidemiological studies should eventually lead to their early diagnosis, optimal treatment, and possible prevention.


Animal experiments on the question of the renal toleration of the horse chestnut saponin aescin.

The possibility that aescin might have a nephrotoxic side effect has been investigated by clearance studies in kidneys of healthy rats and by toleration studies in rats with damaged kidneys. The effect of aescin, both free and albumin-bound, on renal tubular transport processes was studied in the model of the isolated, artificially perfused frog kidney. The rates at which different concentrations of aescin were bound to rat plasma proteins were determined in vitro. The clearance of i.v. aescin was 13% of creatinine clearance and 7% of p-aminohippurate (PAH) clearance; this rules out the tubular secretion of aescin. No deaths occurred among aminonucleoside-damaged rats given i.v. sodium aescinate 2.2 mg/kg, but rats damaged with mercuric chloride or uranyl nitrate had exactly the same mortality rate as those given 2.2 mg/kg i.v. of sodium aescinate alone. The rats received four injections  in all of aescin 0.35 mg/kg i.v., given at intervals of two days. Aescin had no effect on renal damage caused by aminonucleoside, mercuric chloride or uranyl nitrate. Aescin concentrations of 0.2 mg/l and 2.0 mg/l in the perfusion fluid increased the excretion of Na+ and glucose by the frog kidney and reduced the reabsorption of both these substances. With a sodium aescinate concentration of 5 mg/l the production of urine ceased. When 1% (w/v) of albumin was added to the perfusion fluid, even sodium aescinate 5 mg/l had no effect on the tubular transport of Na+, glucose and water. The fact that about 50% of aescin was not bound to plasma protein in vitro suggests that some of the small amount of aescin in the glomerular filtrate is reabsorbed in the tubules.


Synthesis and anti-inflammatory activity of 3,3a-dihydro-2H,9H-isoxazolo [3,2-b] [1,3]benzoxazin-9-ones and related compounds.

A series of 3,3a-dihydro-2H,9H-isoxazolo[3,2-b]-[1,3]benzoxazin-9-ones was synthesized and evaluated for anti-inflammatory, antipyretic and analgesic activity. Since many of these compounds exhibited promising activity, particularly in the anti-inflammatory tests, a number of homologous 2,3,4,4a-tetrahydro-10H-1,2-oxazino[3,2-b]-[1,3]benzoxazin-10-ones and one 3,4,5,5a-tetrahydro-2H, 11H,-1,2-oxazepino [3,2-b][1,3]benzoxazin-11-one, the 9-chloro analog, were also prepared and evaluated. The expanded ring members were generally less active than the tricyclic compounds containing the isoxazolidine ring.


2,3-Dihydro-9H-isoxazolo[3,2-b]quinazolin-9-ones and 3,4-dihydro-(1,2)-oxazino [3,2-b]quinazolin-10(2H)-ones.

Two series of compounds, 2,3-dihydro-9H-isoxazolo[3,2-b]quinazolin-9-ones and 3,4-dihydro-(1,2)-oxazino-[3,2-b]quinazolin-10(2H)-ones, were synthesized and evaluated for anti-inflammatory, antipyretic and analgesic activity. The isoxazolo compounds were generally more active than their oxazino homologs. Three compounds, i.e., 2,3-dihydro-9H-isoxazolo [3,2-b]quinazolin-9-one (W-2429) and its 2- and 3-methyl congeners, were the most active of all compounds tested in this study. On the basis of the biological results herein reported, W-2429 is considerably more effective than acetylsalicylic acid in inhibiting carrageenan-induced edema and in reducing brewer's yeast-induced fever in rats. Also, it was found to be more potent than propoxyphene hydrochloride in the Randall-Selitto test for analgesic activity.


Absorption, distribution and metabolic fate of 2,3-dihydro-9H-isoxazolo-[3,2-b]quinazolin-9-one (W2429).

After oral administration to rats, mice, beagle dogs and human volunteers, 2,3-dihydro-9H-isoxazolo [3,2-b]-quinazolin-9-one (W 2429) is readily absorbed. The initial half-lives for the elimination from the circulation of these four species are about 240, 20, 40 and 120 min, respectively. Studies in the rat, using 9-14C-W-2429 and 3a-14C-W-2429, showed that more than half of the radioactivity is excreted in the urine. The major urinary metabolite in the rat and dog is a conjugated form of W-2429. Metabolic cleavage of the pyrimidone ring of W-2429 yields 3-(o-carboxyphenylimino)isoxazolidine, which in turn is converted to anthranilic and malonic acids. Anthranilic acid is acetylated and hydroxylated, and these products are excreted partly in the form of their glycine and glucuronic acid conjugates. The isoxazole ring of W-2429 is also dehydrogenated during metabolism to yield 9H-isoxanzolo-[3,2-b]quinazolin-9-one.


Toxicological investigation of 2,3-dihydro-9H-isoxazolo[3,2-b]quinazolin-9-one (W-2429). Acute and subacute toxicity in mice, rats and dogs.

The acute and subactue toxicity of 2,3-dihydro-9H-isoxazolo[3,2-b]quinazolin-9-one (W-2429), a non-narcotic analgesic agent, was investigated in mice, rats and dogs. The subacute toxicity study was conducted by repeated oral administration of the compound for 30 days. Treatment with W-2429 was well tolerated by rats as well as dogs. In the dog, the only signs of toxicity observed were decreased appetite and salivation at 100 mg/kg/day. No other significant evidence of physical, chemical, gross or histopathologic change was observed.


Correlation of surface receptors with histological appearance in 29 cases of non-Hodgkin lymphoma.

The receptor patterns of cell suspensions from 29 cases of non-Hodgkin lymphoma were correlated with the histology of the nodes from which the cells were taken. Twenty-two were judged to be predominantly or largely B-cell, and because of this preponderance these were divided by a method based on the distribution of surface immunoglobulin and the expression of Fc and C3 receptors. "Mature" B-cell and B-mixed tumours showing capping surface Ig with Fc and/or C2 receptors correlated well with a nodular growth pattern, and consisted of what Rappaport (1966) calls "poorly differentiated" lymphocytes equivalent to the "small cleaved" cells as defined by Lukes and Collins (1975). Ten of the 14 patients in this receptor category are alive between 12 and 30 months after diagnosis. Receptor-silent and "immature" B-cell tumours with non-capping surface Ig correlated predominantly with the Rappaport histiocytic lymphoma and Lukes and Collins' large cleaved and large non-cleaved lymphomas, though these histological categories also included a wide variety of other receptor types such as T-cell, Receptor-overlap and the single true Macrophage tumour. Five of the 11 patients with receptor-silent or immature B-cell tumours are alive between 7 and 15 months after the diagnosis. Diffuse mixed and diffuse poorly differentiated lymphocytic lymphomas in Rappaport's classification correlated poorly with receptors, mature and immature B-cell tumours being equally represented.


Alleviation of carrageenan-induced hepatotoxicity and acronecrosis by aprotinin.

Carrageenan was found to be hepatotoxic in mice. Raised serum transaminase activity after i.p. injection of carrageenan was correlated with histopathological changes in the liver. These included necrosis of individual hepatocytes and focal areas of necrosis, with associated fibrin thrombi, 12 h after carrageenan injection. Increased mitotic activity was observed at 72 h and extramedullary haemopoiesis was noted at Day 5. Acronecrosis, a further manifestation of intravascular coagulation, was evident within 24 h of carrageenan injection, becoming clearly demarcated by Day 5. Treatment with the anti-protease aprotinin alleviated both the hepatotoxicity and the incidence and extent of acronecrosis induced by carrageenan. The possible mechanism underlying the in vivo toxicity of carrageenan and its alleviation by aprotinin is discussed in the light of these and other findings.


[Severe infections by Haemophilus influenzae in children].

Severity and increasing incidence of serious infections due to Haemophilus influenzae in children have been stressed in recent publications. An analysis of the clinical records of the Department of Pediatrics, Hospital Roberto del Río (Santiago, Chile) was made in order to gather information about frequency and clinical feature of this kind of infections in our environement. 120 children under 3 years of age in whom H. influenzae was isolated in samples of one or more of the following sources: CSF, blood, bone  marrow, pleural and synovial fluids, were admitted from January 1970 to March 1976. Among the different syndromes observed, bacterial meningitis (83.3%) was associated with other localizations in 27%. Empyema (12.5%) was often (46.6%) associated with meningitis. Both clinical entities were the most common and with a definite tendency to increase their frequency in last years. Cultures of CSF, blood and bone marrow were considered effective tests for diagnosis in severe infections due to H. influenzae. Although precise incidence figures may not be obtained from the present data, this kind of diseases may be considered frequent and severe (mortality: 26.6% in this study).


Granulocytic progenitor cells in aplastic anaemia.

The characteristics and the concentration of granulopoietic colony forming cells (CFC) were examined in 22 patients with aplastic anaemia at different stages of their disease. Additionally the ability of the patients' peripheral leucocytes to elaborate factors necessary for colony stimulation in vitro (CSA) was studied. The ability of the patients' cells to generate CSA was shown to be unaffected. However, the incidence of CFC within the marrow and peripheral blood suspensions was significanlty reduced in all patients. The results suggest a reduced compartment size of CFC even in those patients who have recovered from aplastic anaemia. This may indicate that the disturbances in the preceding compartments of the haemopoietic cell renewal system still persist after recovery from the acute bone marrow failure.


Stimulation of human haemopoietic cells by colony stimulating factors: adherent cell dependent colony stimulating activity in human serum.

The number of granulocyte-macrophage clones formed in agar culture of bone marrow is dependent on levels of colony stimulating activity (CSA) a proposed in vivo haemopoietic regulator. A dose-response relationship for stimulation of human haemopoietic cells by CSA is demonstrated, which could be explained by thresholds of stimulation to cell division following a normal distribution. A simple method for the comparison of activities of test and control sources of CSA is presented. The apparent potentiating effect of the addition of two sources of CSA is explained by this dose-response relationhip. Haemopoietic cells from patients with chronic granulocytic or acute myeloid leukaemia showed the same dose-response relationship. CSA levels in normal human sera were greatly reduced by assay in the absence of adequate numbers of bone marrow "adherent cells" (cells adherent to nylon or plastic) or peripheral blood leucocytes, suggesting the presence of two kinds of CSA in human serum, one dependent on the presence of bone marrow adherent cells and one effective in their absence. Reduction of numbers of nonspecific esterase positive cells in the bone marrow sample correlated with reduction in the stimulating effect of serum. In all sera tested, adherent cell dependent CSA was the major component.


Acid esterase in human lymphoid cells and leukaemic blasts: a marker for T lymphocytes.

A non-specific acid alpha-naphthyl-acetate esterase activity was investigated in human lymphoid cell populations from tonsils, blood, thymus and in different leukaemias. Four patterns have emerged. (i) The vast majority of T lymphocytes (peripheral blood, tonsils) showed a localized, intense reaction product ("T-like"). (ii) A thymocyte subpopulation expressed faint, localized enzyme activity ("Thy-like) but the majority of thymocytes showed no esterase activity. Some cells from acute lymphoblastic leukaemias with thymocyte surface characteristics had a "Thy-like" appearance. (iii) Most B lymphocytes and cells from chronic lymphocytic leukaemias were esterase negative. No activity was seen in mitogen activated peripheral blood T and B lymphoblasts from peripheral blood and in leukaemic blasts from the common form of childhood acute "lymphoblastic" leukaemia. (iv) Myeloid cells, including peripheral blood monocytes, and blast cells from acute myeloblastic and chronic granulocytic leukaemias showed an intense, diffuse reaction product (M-like). It is concluded that the modified esterase technique is a convenient marker for small mature human T lymphocytes in tissue sections and smears. It may also be helpful in the differential diagnosis of acute lymphoblastic leukaemia with T characteristics, the common form of acute "lymphoblastic" leukaemia and acute myeloblastic leukaemia.


Studies of von Willebrand factor: effects of different kinds of carbohydrate oxidases, SH-inhibitors and some other chemical reagents.

The effects of several kinds of carbohydrate oxidase, SH-inhibitors and some other chemical reagents on the activities of von Willebrand factor, factor VIII procoagulant and factor VIII-related antigen were studied. Factor VIII procoagulant and von Willebrand factor activities were both inhibited by galactose oxidase, p-hydroxymercuribenzoic acid, 2,4,6-trinitrobenzensulfonic acid and sodium periodate, alpha-Mannosidase, N-ethylmaleimide and phospholipase C inactivated factor VIII procoagulant but not von Willebrand factor activity. Dithiothreitol had little effect on factor VIII procoagulant activity but reduced significantly that of von Willebrand factor. It is suggested that galactose and the thiol and epsilon-aminogroup groups of lysine may play an important role in both factor VIII procoagulant and von Willebrand factor activity. Mannose may be responsible for the factor VIII procoagulant activity but not for the von Willebrand factor activity. The Laurell rocket heights of factor VIII-related antigen rose with increasing concentration of galactose oxidase, 2,4,6-trinitrobenzenesulfonic acid or sodium periodate. Gel filtration experiments showed that factor VIII-related antigen may be dissociated into subunits by galactose oxidase but not by 2,4,6-trinitrobenzenesulfonic acid or sodium periodate.


Changes in electrophoretic mobility of human factor VIII-related antigen: evidence for subunit structure.

Therapeutic factor-VIII concentrates were found to have factor VIII-related antigen (FVIIIRAg) with an electrophoretic mobility faster than that of plasma using two-dimensional crossed immunoelectrophoresis. Immediately after infusion of factor-VIII concentrates into patients, the electrophoretic mobility of FVIIIRAg in the patients' plasmas was increased to that of the antigen in the infused concentrates. Two hours after infusion, a proportion of the antigen had an electrophoretic mobility intermediate between that of the pre-infusion antigen and that of the concentrate antigen, and by 24 h after infusion the reversion of electrophoretic mobility to pre-infusion values was complete. The return of electrophoretic mobility to normal did not occur in vitro after 24 h. In vitro mixing experiments between pre-infusion plasma and concentrate resulted in antigen with a range of intermediate mobilities which were related to the relative proportions of slow and fast antigen in the mixture. In vitro mixing experiments with slow and fast antigen separated from intermediate purity factor VIII concentrate by agarose gel filtration resulted in the formation of a relatively large proportion of antigen with intermediate electrophoretic mobility. The most reasonable interpretation of the results is the formation of hybrids between the two electrophoretically different populations of antigen. This implies that VIIIRAg normally exists in a polymeric form which can spontaneously dissociate into the exist in equilibrium with a pool of partially and/or completely dissociated subunits.


[Mechanism of passive enhancement].

The  authors present an original mechanism of the passive enhancement phenomenon which takes in account recent data, obtained in the rat and in the mouse, concerning specificities of enhancing Ig. Antibodies directed against "serological defined" antigens of the graft are not required for enhancement. An enhancing serum, deprived from anti "SD" antibodies still retains the ability to specifically block the target strain Fc receptor without any effect on lymphocyte harvested from strain carrying other major histocompatibility loci. The relationship between the Fc receptor of lymphocytes and Ia antigens are discussed since the enhancing serum deprived in anti-"SD" antibodies by absorption procedures could be referred as an anti-Ia serum. After having reviewed the data on the impairment of the immune response of enhanced host against the graft, an hypothesis involving graft lymphocytes Fc receptor blockage and abnormalities of the T-B lymphocytes cooperation in the enhanced animal is developped.


Unit responses in the frog's caudal thalamus.

Single unit microelectrode recordings were made in the caudal thalamic region of the frog, Rana pipiens, from a sample of multimodal sensory units which included monocular, binocular, tactile, and spontaneous types, and which showed a wide variety of receptive field sizes, response rates, preferred stimulus sizes habituation rates, and velocity and tactile sensitivities. A number of special response properties were occasionally observed, including directional sensitivity, stationary object sensitivity, afterdischarges, and visual and tactile inhibitory fields. Computer analysis of spontaneously active units revealed four types: regular, exponential, bursting, and multimodal.


Synaptic innervation of sympathetic ganglion cells in the bullfrog.

The synaptic innervation of the ganglion cells in the ninth and tenth paravertebral sympathetic ganglia of the bullfrog was investigated by histochemical and electron microscopic techniques and by intracellular recording. The neurons were unipolar and most ganglion cells were innervated by a single preganglionic axon. The preganglionic fiber stained for acetylcholinesterase and was observed to spiral around the axon hillock of the ganglion cell before arborizing and making synaptic contact with the neuron. Most  synapses were located on the soma near the axon hillock region, with features typical for cholinergic junctions. The axosomatic location of the synapses was manifested physiologically by a decrease in membrane resistance (increased conductance) at the peak of the fast EPSP (excitatory postsynaptic potential) and by a demonstrable reversal potential for the fast EPSP.


Identification of small intensely fluorescent (SIF) cells as chromaffin cells in bullfrog sympathetic ganglia.

Small intensely fluoresent (SIF) cells were investigated in the ninth and tenth paravertebral sympathetic ganglia of the bullfrog using histochemical and electron microscopic techniques. Fluorescence histochemistry revealed that clusters of SIF cells are sparsely distributed in the ninth and tenth ganglia; the clusters were usually located in the vicinity of blood vessels. Fluorescent processes were not observed emanating from SIF cells. The clusters stained positively for the chromaffin reaction indicating that SIF cells are chromaffin cells. Ultrastructurally, the SIF-chromaffin cells in the sympathetic ganglia appeared virtually identical to the chromaffin cells in the adrenal gland; this includes two cell types that appear morphologically the same as the epinephrine and norepinephrine containing chromaffin cells in the adrenal gland. Efferent synapses from the SIF-chromaffin cells in sympathetic ganglia to sympathetic ganglia to sympathetic neurons were not observed. The SIF-chromaffin cells in bullfrog sympathetic ganglia did not have the morphological characteristics of interneurons; it is suggested that they may function as extra-adrenal chromaffin tissue.


Microiontophoresis of 5-hydroxytryptamine, epinephrine, and prostaglandin E1 on spinal neurons in the frog.

5-Hydroxytryptamine (5-HT) and epinephrine were applied by microiontophoresis to single neurons in the isolated spinal cord of the frog. 5-HT depressed all but two of the responsive cells, whereas the response to epinephrine consisted exclusively of depression. 5-HT action was more marked than that of epinephrine on most cells. With either compound, responseve units were diffusely distributed throughout the tissue. While it was proven that prostaglandin E1 (PGE1) exerts a direct excitatory action on spinal neurons, no evidence of an antagonism between PGE1 and the monoamines was obtained. These findings provide additional support to the hypothesis that 5-HT and epinephrine are transmitters in the frog spinal cord. The possibility that PGE1 may 'modulate' the responsiveness of spinal neurons to the monoamines was not confirmed.


Extravascular lung water accumulation in patients following coronary artery surgery.

We studied patients undergoing A-C Bypass with haemodilution. The bubble oxygenator was primed with either two units of plasma and lactated Ringer's solution (PLASMA) or with lactated Ringer's solution (RINGER'S) alone. We found no difference in pulmonary function or lung water determinations between the Ringer's and the Plasma groups. When all patients were grouped together we found no significant increase in lung water (ETVL)5 immediately post-operatively. This suggests lung water did not increase during cardiopulmonary bypass. By the following morning there was a highly significant increase in lung water which was related to changes in the balance between hydrostatic pressure and colloid osmotic pressure and which continued through the second post-operative day. Pulmonary dysfunction, as measured by gas exchange, was not a major problem except in one patient whose lung water increase exceeded 3 ml H2O/kg of total body weight (52 per cent increase) and in whom there was increased shunting. We consider the increase in lung water important, since it may reduce lung compliance and further lung water accumulation. Since the increased lung water was associated with a change in the balance of Starling's forces (PMV - COPMV), treatment designed to reduce that balance should reduce lung water accumulation.


Specific active immunochemotherapy in lung cancer: a survival study.

A radomized clinical trial of chemotherapy, immunization and immunochemotherapy among 55 patients with stages I and II carcinoma of the lung is reported. The survival rate in the immunized groups was significantly better (P = 0.001) than that in the nonimmunized groups. The results are discussed in the light of the reactivity of the patients to the specific cancer antigen.


Possible effects of non-HLA antibodies in common typing sera on HLA antigen frequency data in leukemia.

Selective adsorption of several common "monospecific" HLA typing sera with HLA typed platelets, purified B lymphocytes, cultured lymphoid cells, or lymphocytes from patients with active chronic lymphocytic leukemia demonstrated that many of these sera contain antibodies to non-HLA antigens. Antibodies were detected to antigens present on peripheral blood B-lymphocytes, cultured lymphoid cells and leukemic cells from patients with both myelocytic and lymphocytic forms of leukemia but absent from T-lymphocytes and platelets. Since these kinds of antibodies appear to be present in a large proportion of common HLA typing sera, caution should be used in interpreting all data related to HLA antigen expression in leukemia.


The treatment of advanced histiocytosis-X with sequential hemibody irradiation.

A patient with systemic histiocytosis was treated with hemibody irradiation, vincristine, and prednisone. The patient died of an extensive peripheral neuropathy. An autopsy revealed gross histiocytosis-X involvement of the unirradiated tissues, and no evidence of disease within the field of irradiation. A treatment protocol employing sequential hemibody irradiation is discussed.


Approaches for the isolation of biologically functional tumor-associated antigens.

Melanoma-associated antigens were isolated from human melanoma cells in long-term tissue culture and from the spent culture fluid of these cells propagated in chemically defined, serum-free media. The 3 M KCl extracts from such cells and their concentrated spent culture media elicited specific delayed cutaneous hypersensitivity reactions in patients with malignant melanoma but not in patients with other neoplasms. HLA antigens present in these extracts could be specifically removed by ultracentrifugation in KBr at a density of 1.23 g/ml. Purification of melanoma-associated antigens was achieved by this step, followed by ion-exchange chromatography and preparative isoelectric focusing on Pevikon C870. Another approach is described for the isolation of carcionembryonic antigens from metastatic lesions with an approximately 70% yield utilizing the least denaturing procedures, which avoid lyophilization and involve essentially 0.9% NaCl solution extraction, specific adsorption, elution from concanavalin A Sepharose, and subsequent gel-exclusion chromatography on Ultrogel AcA 22. For effective isolation of carcinoembryonic antigens freely shed from cultured cells derived from a primary colon tumor, a system was devised based on the use of Amicon hollow fiber culture units, in which cultured tumor cells were introduced in the extracapiliary spaces of such a unit. The extracapillary fluid, containing carcinoembryonic antigens but no fetal calf serum components, is removed and further purified by affinity chromatography.


IgE mediated hypersensitivity in ageing.

The serum IgE concentration is significantly lower in aged as compared with young people. This is more pronounced in males than in females (P less than 0-05). In fifteen aged (greater than 70 years) compared with fifteen young subjects (less than 40) the specific IgE antibody response to an injection of diphtheria toxoid was significantly reduced (P less than 0-01). The  minimum concentration of anti-IgE antibody able to induce a weal and flare reaction when injected intradermally, was comparable in the two age groups. However, the diameter of the weal reaction was significantly reduced in the aged. It is concluded that the reduced incidence of atopic symptoms in old people might be secondary to an anomaly of both the immune system and the mast cells.


Preparation of a phospholipase C-antihuman IgG conjugate, and inhibition of its enzymatic activity by human IgG.

We labeled IgG with phospholipase C, using 1-cyclohexyl-3-(2-morpholinoethyl)-carbodiimide. Enzymaticactivity of the resulting conjugate was inhibited when it was complexed with human IgG, but rabbit or goat IgG was not effective in suppressing the enzyme activity. Normal erythrocytes were used as substrate for the enzyme, enzymatic activity being assessed by measuring the release of hemoglobin. The substrates for phospholipase C are phospholipids, which are major components of the erythrocyte membranes. Hence, the phospholipids in the membranes are viewed as being "immobilized." Perhpas such immobilization of substrate may be a requisite to the inhibition phenomenon.


Relationship between anti-DNA antibodies complement consumption and circulating immune complexes in systemic lupus erythematosus.

Eighty-nine sera from nineteen patients with systemic lupus erythematosus (SLE) have been studied to determine the relationship between levels of DNA-binding activity, complement consumption and evidence of circulating immune complexes. There was a good correlation between the height of DNA binding, a rising C3i and a reciprocal fall in C3, C4 and CH50 levels.  These latter measurements provided useful supplemental information when studied serially. There was a good correlation between the results of the various methods used for the detection of circulating immune complexes, and these were found in almost half the sera with DNA binding over 70%. It is concluded that serial studied of DNA binding, complement levels, and direct tests for immune complexes, may provide valuable information in the management of patients with SLE.


The relationship of defective cell-mediated immunity to visceral disease in systemic sclerosis.

Phytohaemagglutinin-induced lymphocyte transformation and circulating thymus-dependent (T) lymphocyte numbers were studied in twenty-eight patients with systemic sclerosis (SS), in fifty normal controls and eleven elderly controls. Patients with SS were found to have impaired lymphocyte transformation responses which showed a positive correlation with both the number of circulating T lymphocytes and the extent of visceral involvement by the disease. This defect of cell-mediated immunity could not be attributed to the effects of increasing age, corticosteroid treatment, iron and folate deficiency or inhibitory serum factors and may have pathogenetic implications for the disorder.


Immunological studies of patients with asbestosis. II, Studies of circulating lymphoid cell numbers and humoral immunity.

As part of an overall assessment of immunological function, several aspects of humorial immunity and circulating lymphocyte subpopulations were evaluated in a group of twenty-six patients with radiographic evidence of parenchylmal asbestosis. Statistical comparisons were made between the patient group and a comparable group of forty-five controls. Both the percentages and absolute numbers of circulating T lymphocytes were significantly reduced in the patient group compared with controls. Significant elevations of salivary secretory IgA and of serum IgA, IgG, IgM and IgE were noted amongst the patients compared with the controls. Non-organ-specific autoantibodies and cold-reactive lymphocytotoxins were present in high frequency in the patients' sera. Neoplasms were detected in four of the patients. The possible significance of these findings is discussed.


Depletion of circulating T lymphocytes in pregnancy.

Changes were assessed in lymphocyte sub-populations in various stages of human pregnancy. The percentage and absolute number of E-RFC decreased during pregnancy. There was a concomitant rise in the percentages of EAC-RFC and cells bearing SmIg with little change in their absolute numbers. EAC-RFC continued to rise post-natally.


Effect of corticosteroids on exercise-induced lymphocytosis.

Eight subjects ran on a treadmill at 8 miles per hr for 10 min. All developed lymphocytosis with predominant effect on the B cells. This was repeated 5 hr after receiving 60 mg of Prednisone. The lymphocytosis of both T and B cells were suppressed. When this was repeated 2 hr after receiving Prednisone, only lymphocytosis of the T subpopulation was suppressed. It was concluded that corticosteroid administration could suppress entry of lymphocytes into the circulation, with preponderant effect on the T subpopulation.


Co-operation between T and B lymphocytes from human tonsils in the response to mitogens and antigens.

Purified B lymphocytes obtained from human tonsil cell populations by removing E rosette-forming cells by density sedimentation did not proliferate at three days in response to PHA and Con A, but showed a significant 3H-labelled thymidine incorporation when the PHA response was assessed at day 6 of culture. The 6th-day responses, which was completely abolished by the reduction of T-cell contamination to less than 0-1% by re-rosetting and a second separation, was due in part to a direct activation by PHA of contaminating T cells and in part to a T cell-mediated B-cell response. When purified B cells were stimulated for 3 days by PHA in the presence of an equal number of autologous or homologous mitomycin-treated T lymphocytes a highly significant uptake of 3H-labelled thymidine was demonstrated. The majority of blast cells obtained at day 4 in  these cultures were unable to form E rosettes and showed surface immunoglobulin by immunofluorescence stain. This response was markedly decreased by previous treatment of B cells with mitomycin C and it was abolished when B cells were killed by heating at 56degrees C for 1 hr. Purified B lymphocytes from human tonsils did not respond in vitro when cultured for 6 days in the presence of soluble antigens (PPD and  Candida). However, a highly significant response to the same antigens could be demonstrated when B cells were cultured in the presence of autologous mitomycin-treated T cells. These models of T-B co-operation could provide an interesting tool for studying the differentiation and antibody production in vitro of human B lymphocytes.


Lack of subclass selection during density purification of human lymphocytes.

The percentage of acid alpha-naphthyl acetate esterase (ANAE) marker-carrying lymphocytes (T-lymphocytes) was determined directly from the blood, after density purification of lymphocytes over Ficoll-Isopaque and removal of monocytes by iron powder plus magnet. The effect of Ficoll-Isopaque centrifugation was insignificant; neither did the iron powder plus magnet procedure increase the relative proportion of the T cells in these preparations. We therefore conclude that in optimal conditions there is no subclass-specific enrichment of T or B lymphocytes during the purification procedure.


Spontaneous rupture of a coronary artery with false aneurysm formation. Successful surgical repair.

A patient with diffuse atherosclerotic coronary arterial disease was demonstrated to have a spontaneous rupture of the proximal right coronary artery, with formation of a false aneurysm. This was recognized at angiographic study, and the patient subsequently underwent a revascularization operation with suture ligation of the aneurysm.


New concepts in prevention and treatment of sunburn.

Effective topical sunscreens are available in Australasia, but are some more effective and acceptable than others? For those who demand an early tan and longer protection there still remains some hope that effective topical applications may become available. Acute sunburn must be assessed from a general medical viewpoint. Severe sunburn requires a short "dermatological" course of systemic steroids. Prostaglandins and antiprostaglandins may have a role in the future treatment of sunburn.


Suppressor T cells in low zone tolerance. I. Mode of action of suppressor cells.

Low zone tolerance (LZT) to bacteriophage fd seems to be a type of tolerance which is primarily caused by suppressor T cells. The aim of this paper is to analyze their mode of action. For the induction of antigen-specific suppressor cells in hydrocortisone pretreated CBA mice, we use tolerogenic and immunogenic doses of antigen. Suppressor activity can be demonstrated upon transfer of spleen cells into normal syngeneic mice. After immunization these animals are unable to produce IgG antibody against phage fd, whereas the IgM response is not suppressed; The half-life of transferred suppressor cells in nonimmunized animals is 5--6 weeks. The target of suppression are unprimed T helper cells, whereas primed helper cells cannot be blocked. T helper cells become "resistant" to suppression 18--36 h after contact with antigen. Differentiation from unprimed B into B memory cells is unaffected, yet under suppression conditions persisting B memory cells are blocked in IgG production. The experimental data are incorporated into a model of LZT.


Limulin (Limulus polyphemus lectin): mitogenic effect on human peripheral lymphocytes.

The lectin from hemolymph of Limulus polyphemus was purified by affinity chromatography on insolubilized bovine submaxillary mucin. The purity of the protein was checked by crossed immunoelectrophoresis. Agglutination of human red blood cells was completely abolished after neuraminidase treatment, while other cells were still agglutinable after the same treatment but required a higher concentration of lectin. Limulin was able to simulate about 50% of human peripheral lymphocytes. This mitogenic effect could be inhibited by bovine submaxillary mucin but not by the disialylated mucin. Related to the known oligosaccharide-binding specificity of limulin and of the other nonspecific activators of lymphocytes, the authors suggest that lymphocyte stimulation is triggered by binding to a glyco-conjugate bearing the following carbohydrate chains: NANA leads to GalNac leads to or NANA leads to Gal leads to GlcNAc leads to Man.


Restoration of the T lymphoid system of nude mice: different regeneration of neonatal and adult thymuses.

When a neonatal thymus and an adult (reticuloepithelial) thymus from normal mice are simultaneously grafted to individual adult nude mice, the host-derived T cell precursors regenerate the neonatal thymus more efficiently than the adult (reticuloepithelial) thymus. Thus, this is a direct cause for the poor restoration of the T lymphoid system of nude mice by adult and/or reticuloepithelial thymus grafts.


The induction of carrier-specific helper cell tolerance in presensitized rats.

Lewis rats rendered tolerant to sheep IgG (SGG) show a markedly reduced antibody response to the 2,4,6-trinitrophenyl (TNP) hapten when later challenged with TNP-SGG. We have previously shown that this effect is due to functional unresponsiveness in the carrier SGG-specific helper T cell population. In this paper we demonstrate that induced helper cell tolerance is also maintained through a secondary immunogenic challenge. Furthermore, rats which are primed to the carrier SGG prior to tolerance induction also show a markedly reduced anti-TNP response upon secondary immunogenic challenge with TNP-SGG. The ability to specifically suppress a secondary response in this manner was found to be relatively long lasting, since rats showed reduced responsiveness when the secondary challenge was delayed for up to 4 weeks after tolerance induction. In addition, rats primed to the hapten (TNP) prior to carrier (SGG) tolerance induction also showed a marked reduction in anti-TNP antibody following challenge with TNP-SGG. These findings imply that helper cell tolerance can be induced in rats even after priming of carrier-specific (SGG) helper cells, or hapten-specific (TNP) B cells. These results parallel our other published findings that IgE responses in presensitized rats can be overcome by helper cell tolerance.


Genetic selection of mice for quantitative responsiveness of lymphocytes to phytohemagglutinin.

A two-way selection was performed in mice according to the quantitative in vitro response of lymph node lymphocytes to the mitogenic activity of phytohemagglutinin (PHA). The foundation population was composed of outbred mice produced by reciprocal mating of equal numbers of mice from four different colonies. The selective breeding was carried out by mating of mice at each generation giving the best or the lowest response, respectively. The progressive interline separation produced by 6 generations of selective breeding demonstrates that responsiveness to PHA is submitted to polygenic regulation. The heritability of the character investigated is 0.28 +/- 0.08. The interline separation is also found with another T mitogen, concanavalin A (Con A). In spleen cells PHA and Con A produce a similar interline difference. In contrast, the purified protein derivative of tuberculin (PPD) stimulated both lines equally, and E. coli lipopolysaccharide gave only a slightly higher response in high line. This finding implies that our selection based upon response to PHA did not influence B cell function.


Reduced in vitro response to concanavalin A and lipopolysaccharide in senescent mice: a function of reduced number of responding cells.

The proliferative capacity of spleen cells from C57BL/6J female mice of various ages (3-28 months) to the polyclonal mitogens concanavalin A (Con A) and lipopolysaccharide (LPS) was examined. It was found that both the T and B cell population of the spleen demonstrate an age-related decrease in their capacity to respond in vitro. Peak responses to both mitogens occurs at about 1 year of age. This age-related reduction in response is expressed in the degree of incorporation of [3H]thymidine into DNA, the total number of cells generated in vitro, the number of labeled cells per culture and the number of blast cells per culture. The day of peak response in vitro does not change with age. Studies of the cell cycle of cells responding to Con A and to LPS from 12 and 28-month-old mice demonstrate that the generation time of individual proliferating cells does not alter with age. Nor does it differ for the B cells responding to LPS or the T cells responding to Con A. These studies also demonstrate that the proliferating cells from senescent mice are equally capable of repeated cell divisions as are the cells from the 1-year-old adult mouse. It is concluded that the defect in senescent mice which leads to a reduced in vitro response to the polyclonal mitogens LPS and Con A is a reduction in the number of responding cells and not an alteration in the capacity of those cells which do respond to divide.


Functional development of the interacting cells in the immune response. III. Role of the neonatal spleen.

Neonatal splenectomy and congenital absence of the spleen were shown to be associated with lack of primary IgM antibody synthesis, deficient bone marrow-thymus cell synergism. altered mitogen responsiveness and depressed homing patterns of thymocytes to the spleen. Using congenitally asplenic animals, altered B-T cell cooperation was manifest at the T cell but not B cell level. This correlated with the ability of thymus cells from either congenitally asplenic or neonatally splenectomized (NSx) animals to respond to the B cell mitogen lipopolysaccharide although there were no detectable Ig=ells present. To determine the role played by the spleen in the development of T cell function, NSx animals were given either irradiated or normal spleen grafts. Both irradiated and unirradiated grafts restored normal B-T cooperation and normal mitogenic responses of thymus cells. However, neither type of spleen graft was successful in restoring normal homing patterns to the spleen. It is concluded that the splenic microenvironment influences T cell maturation very early in life and that only some of the effects attributable to the absence of the spleen can be reversed by the reintroduction of this tissue as a graft.


Functional renal failure and haemorrhagic gastritis associated with endotoxaemia in cirrhosis.

Forty-three patients with cirrhosis and ascites, 21 with normal renal function, 10 with a progressive functional renal failure (FRF), and 12 with a steady FRF, were investigated for the presence of endotoxaemia by the Limulus lysate test. Endotoxaemia was found in nine patients with FRF and in none of the 21 with normal renal function (P less than 0-01). A positive Limulus test was almost exclusively associated with a progressive FRF (eight of 10 patients) and all but one of them died. Renal function improved as endotoxaemia disappeared in the survivor. Endotoxaemia was also associated with haemorrhage due to acute erosions of the gastric mucosa, being present in six of the seven patients who had this complication. Intravascular coagulation was not found in any patient. The Limulus test was positive in the ascitic fluid in 18 of 21 patients tested, although only two of them had peritonitis. These results suggest that endotoxaemia may play a critical role in the development of progressive renal failure and haemorrhagic gastritis in cirrhosis, and emphasise the potential risk of procedures involving reinfusion of ascitic fluid.


[Immunologic development disorders and disease incidence].

Interference with any organ system during development leads to permanent damage. Severe disease or starvation during the first four months of extrauterine life lead to a persistent deficiency of cell mediated immunity, which changes the life expectancy and later disease patterns in population groups. Severe intercurrent disease, starvation or trauma later in life lower cell mediated immunity only temporarily.


[Physiologic and clinical manifestations of brain-dominance (author's transl)].

The effects of brain-dominance in psychology, electrophysiology and the axial muscles are described. 1. Left-sided vascular hemispheric brain-distrubances, with or without aphasia, reduce, compared with arteriosclerotics, without focal signs, verbal, action-and total IQ, those on the right side only the action and total IQ. When comparing right- and left-sided frontal, frontoparietal and frontotemporal vascular disturbances - with or without a aphasia-, the left-sided frontotemporal lesions had a lower action- and verbal IQ, even if there were no signs of aphasia. In children aged between 12 and 40 months we found no correlation between the degree of motor dominance and mental development. Among children with delayed speech development--and therefore also in children with subnormal development--the number of lefthander was significantly higher than with the other children. 2. One can show electromyographically that, when a muscle is voluntarily contracted, there is simultaneous contraction of the same muscle on the other side. This contralateral motorspread happens more often from the stimulation of the dominant side to the subordinated side than vice versa. Ipsilateral somato-sensory cortical response is more common when stimulating the dominant than the subordinated ulnar nerve and develops ontogenetically parellel with right- or left-handedness. 3. Stabilographic registration can show a right-sided prevalence of swing of the vertical axis of the body, which probably is related to a lower irritability of the vestibular apparatus on galvanic stimulation. With the eyes open, the right-sided deviation of the bodyaxis increases which can be explained by greater functional strength of the right visuomoto system, which itself can be shown by the higher frequency of right-sided optocinetic nystagmus.


Co-operation across histocompatibility differences. The role of inhibitory T cells in preventing successful T-B interaction.

The efficiency of interaction of helper T cells with memory B cells of varying histocompatibility types has been studied in an in vitro microculture system. Such studies show that I-A region matching does not necessarily determine that efficient co-operation will take place. Failure to co-operate under circumstances where T and B cells match in I-A can be attributed to radiosensitive suppressor T cells. The nature of the gene differences which provoke the activity of such suppressor cells have also been examined, and it would seem that even single S.D. differences in the MHC are sufficient to generate 'suppressor' T-cell activity.


The generation of memory cells. I. The role of C3 in the generation of B memory cells.

Adult thymectomized, repopulated mice were chronically depleted of circulating C3 by treatment with cobra venom factor after primary immunization with dinitrophenylated haemocyanin (DNP-KLH). This treatment totally abrogated the development of B-cell memory in such mice, as assayed by a co-operative lymphocyte transfer. The failure of memory development appeared to involve impaired precursor proliferation following priming. It was further shown that the localization of DNP-KLH in splenic lymphoid follicles is both antibody and C3-dependent; thymus-deprived mice make sufficient antibody to DNP-KLH to effect follicular localization of the antigen. On the basis of these and earlier observations we suggest that the development of B-memory cells involves the formation of antigen-antibody-C3 complexes on dendritic cells in lymphoid follicles. C3 may serve to stabilize the antigen bridge between dendritic cells and virgin precursors. In complete contrast, C3 depletion had little effect on the functional expression of primed B cells, thus suggesting that only the early stages of B-cell triggering are C3 dependent.


Complications and immunological studies of measles virus infection in antithymocyte-treated hamsters.

A study was done to investigate possible late central nervous system (CNS) complications of latent measles infection in hamsters. Signs of CNS disease, consisting of myoclonus and paralysis, occurred in some weanling hamsters inoculated intraperitoneally at 3 or 9 days of age with antithymocyte serum (ATS) and measles virus, but no late complications in adult life attributable to measles virus were seen. A single series of ATS injections plus an injection of measles virus resulted in sustained antibody formation postulated due to establishment of a latent viral infection, whereas similar treatment with normal rabbit serum plus virus caused no or minimal antibody response. The majority of hamsters receiving ATS as newborns and ATS plus virus as weanlings also did not produce antibody. This differential effect of ATS may be due to combined elimination of suppressor and helper cells in the latter ATS-treated group and of suppressor cells only in the former ATS-treated group. Cellular immunity could not be evaluated since lymphocytes from inoculated and uninoculated hamsters released equal and variable amounts of 51Cr for both infected and noninfected labeled, allogeneic hamster target cells.


Immunology of the infant rat experimental model of Haemophilus influenzae type b meningitis.

The age-related acquisition of serum anticapsular and bactericidal antibodies to Haemophilus influenzae type b observed in rats was similar to that of humans. The antigenic source for this "natural" immunity was not identified since neither pharyngeal infection with H. influenzae b nor enteric colonization by cross-reacting bacteria was detected. Infant rats surviving H. influenzae b bacteremia failed to respond immunologically to the capsular polysaccharide. However, surviving rats demonstrated no impairment of immune responsiveness to this antigen after subsequent immunization with live bacteria in adulthood. In passive protection experiments, antibodies directed against the type b capsular polysaccharide represented the major protective specificity. However, a small protective effect of antibodies to noncapsular antigens also appeared to have been demonstrated.


Study of colour blindness in school children.

Of the 1553 male and 519 female students in schools of Patiala, between the age group of 10 and 15 years, 3.85% males and 0.38% females were found colour-blind. The students were tested by Ishihara Charts, Edridge Green Lantern and then assayed by Pickford Nicolson Anomaloscope and the results were presented in detail. In addition, the affected students were also tested for their acuity of vision and were found normal.