Widespread bone involvement in sinus histiocytosis. Sinus histiocytosis with massive lymphadenopathy is a rare disorder of the reticuloendothelial system with predilection for black children.


Results of reoperation for failed aortocoronary bypass grafts. Thirty-one patients underwent reoperation for failure of one or more previous aortocoronary bypass grafts. Thirty-nine grafts were replaced. Twenty-four grafts were constructed to vessels not thought to be significantly diseased at initial operation. There were no early or late deaths. Postoperative morbidity was comparable to initial prodecures. Of 24 patients followed up for more than six months., 62% clearly experienced improvement without evidence of perioperative or postoperative infarction. Reoperation for failed aortocoronary bypass grafts can be achieved without excess risk, but with long-term results less optimistic than initial procedures.


Acoustic reflex test in neuro-otologic diagnosis. A review of 24 cases of acoustic tumors. Acoustic and other tumors of the cerebellopontine angle are not uncommon, and they usually have otologic symptoms or findings. Early diagnosis depends on a high index of suspicion and a thorough evaluation of patients with suspected tumors. This is a report of 24 cases selected from a group of 184 surgically confirmed tumors. Had the cases been evaluated only on the basis of pure tone or speech audiometry or on the basis of plain roentgenograms, the diagnosis might not have been made. Audiological examination should include the acoustic reflex test. The results of this test indicated a retrocochlear problem (absence or decay of the reflex) in 19 of 24 cases (80%). The test was positive in 11 of 12 patients with normal or near normal hearing and in seven of eight patients with normal x-ray films.


Pathophysiology of endolymphatic hydrops. Endolymphatic hydrops of the nonprogressive type occurs in response to a single traumatic or toxic insult of limited duration and although it may result in permanent deficits in sensorineural function, there is total subsidence of vestibular symptoms. Endolymphatic hydrops of the progressive type, on the other hand, appears to be the result of permanent impairment of endolymph resorption and is caused principally by disorders of the endolymphatic sac. It occurs in Menière's disease, syphilitic labyrinthitis and the delayed hydrops syndrome. In addition to deafness of varying extent, it is characterized by episodic vertigo and sometimes by Hennebert's sign. Histological studies suggest that the acute vertiginous episodes are caused by potassium intoxication following ruptures of the membranous labyrinth and that Hennerbert's sign is caused by vestibular fibrosis.


[Determination of T anb B lymphocytes in patients with rheumatic fever]. The populations of "T" and "B" lymphocytes were evaluated in the present work employing the rosette technique in patients with active rheumatic fever, diagnosed according to Jones' criterion. "B" lymphocytes were found diminished at 7 days after the acute episode of rheumatic fever and increased at 35 days. These findings can be correlated with the hypergammaglobulinemia observed in this type of cases. Although there were wide variations in the quantity of "T" lymphocytes in some patients with rheumatic fever in this study, the porcentual and absolute values of "T" lymphocytes had no modifications when these were compared with the control group. The patients showed leucocytosis when entered the hospital and 7 days after. At 35 days of hospitalization they presented discrete lymphocytosis. Since the patients with rheumatic fever usually receive anti-inflammatory treatment with steroids, and as these drugs are capable of decreasing selectively the "T" lymphocytes, their effect on the kinetics of the lymphocytes in rheumatic fever has to be elavuated in further studies.


Menière's disease - roentgenologic diagnosis. Radiologic diagnosis in Menière's disease should not be based on the vestibular aqueducts tomographic reproducibility. Instead, valuable preoperative information should be given about the size and location of the aqueducts external aperture in relation to the posterior and lateral semicircular canals. In saccotomy the semicircular canals are landmarks for identification of the endolymphatic sac. The periaqueductal pneumatization is demonstrated to be partly decisive for the vestibular aqueducts gross morphology. In Menière's disease either a sparse or a total lack of periaqueductal pneumatization is observed in most of all cases. The development of peri- and infralabyrinthine pneumatization is also decisive for the position of the foveate impression, which houses the extraosseous part of the endolymphatic sac. Its location and size can be evaluated by tomographic characterization of the vestibular aqueducts external aperture.


Thymus-dependent (T) lymphocyte deficiency in progressive systemic sclerosis. Circulating thymus-dependent (T) lymphocytes were estimated in twenty-seven patients with progressive systemic sclerosis (PSS) and in forty-five normal controls using the property of T lymphocytes to form rosettes with sheep red blood cells. The patients with PSS were found to have a reduction of T lymphocytes which correlated with the extent of visceral involvement by the disease, those with the lowest counts having the most extensive disease. These findings support the suggestion that immunological factors may be involved in the pathogenesis of PSS.


Generalized warts and immune deficiency. A case of common variable hypogammaglobulinaemia with associated impairment of cell mediated immunity and severe wart virus infection is described. The defect of cell mediated immunity is thought to have predisposed this patient to the development of persistent wart infection which in turn grossly depressed the body's cellular immunity and thus allowed widespread dissemination of the warts. The rapid restoration of cell mediated immunity which followed the reduction in the antigenic load of wart virus by diathermy treatment was followed by the spontaneous regression of all the patient's warts. This unusual case may provide some insight into the complex relationship between wart virus infection and the immune system of the host.


Unsuspected fungal endophthalmitis diagnosed in vitrectomy specimen. A vitrectomy specimen obtained with the roto-extractor from a diabetic patient with vitreous haemorrhage revealed fungal endophthalmitis on microscopical examination. Endophthalmitis was not suspected before the procedure. Extensive medical examinations failed to reveal any evidence of systemic fungal disease. The case exemplifies endogenous mycotic endophthalmitis of occult origin, the first of its kind, we believe, to be diagnosed in this manner.


Decreased rate of sodium conductance inactivation in the node of Ranvier induced by a polypeptide toxin from sea anemone. The effects of two toxins extracted from the tentacles of Anemonia sulcata on ionic currents have been tested on the nodal membrane of myelinated nerve fibres from Rana esculenta. While external application of Toxin I at 100 muM leaves both specific ionic currents unmodified, Toxin II at 10 muM reacts with a receptor site associated with the sodium conductance inactivation gating. Since internal application by diffusion of Toxin II at a concentration of 700 muM leaves the ionic currents unchanged, the receptor site is most likely located on the external side of the nodal membrane. An equilibrium dissociation constant for the effects of Toxin II was estimated as 20 muM. The on-reaction is fast (rate constant for the on-reaction roughly equal to 3.103 M-1) suggesting a readily accesible receptor site for the toxin. The kinetics characteristics of the sodium currents recorded in the presence of Toxin II suggest that there are at least two steps in the reaction leading to Na+ -channels with the inactivation gate completely immobilized. The relatively fast reversibility of the intermediate stage of the reaction and the rather slow but, in the end, complete reversal of the toxin effects suggest that the toxin acts by modifying the energy profile for the transition "inactivation gate in the open configuration to inactivation gate in the closed configuration." Toxin II at higher concentrations (greater than 100 muM) also inhibits the potassium currents but these effects were not studied in any detail.


Steroid contraceptive agents and immunological reactivity in experimental animals. The immunodepressive activity of widely employed steroid contraceptive agents (SCA's) was evaluated in mice and rats on various humoral and cell-mediated responses. Three different progestagens (lynestrenol, norethindrone or norethynodrel) were administered in combination with the estrogen mestrahese SCA's could significantly reduce the severity of allergic encephalomyelitis in rats, variations in their capacity to interfere with primary response to sheep erythrocytes in mice and anti-mouse erythrocyte autoantibody formation were found. Treatments employed with these SCA's did not reduce tumor allograft resistance in mice and the anti-sheep erythrocyte response in rats. In addition, otherwise immunosuppressive treatments with these SCA's did not modify the mouse response to a T-independent antigen. The possible clinical significance of these results is discussed.


Pulsed nuclear magnetic resonance study of 39K in frog striated muscle. Samples of 1 M KCl solution and 10 samples of intact frog striated muscle were studied at 4-7 degrees C and/or at 21-22 degrees C. Field inhomogeneity was minimized by using small sample volumes and by using a superconducting magnet designed specifically to provide highly homogeneous fields. In the present experiments, magnetic field inhomogeneity was measured to contribute less than 15% to the free induction decay observed for intracellular 39K. The signal-to-noise ratio of the measurements was enhanced by means of extensive time-averaging. The rates of nuclear relaxation for 39K in aqueous solution were 22 +/- 3 (mean +/- 95% confidence limits) s-1 at 4-7 degrees C and 15 +/- 2 s-1 at 21-22 degrees C. For intracellular 39K, (1/T2) was measured to be 327 +/- 22 s-1 and 229 +/- 10 s-1 at the lower and higher temperatures, respectively. The corresponding values for (1/T1) in the same muscle samples were 198 +/- 31 s-1 and 79 +/- 15 s-1 at 4-7 degrees C and at 21-22 degrees C, respectively. These results for 39K are similar to those previously obtained for intracellular 23Na. Since less than 1% of the intracellular 23Na has been estimated to be immobilized, fractional immobilization of intracellular 39K is also likely to be insubstantial.


[Specificity of the effect of growth hormone on DNA concentration in the nuclei of the lymphoid cells of hypophysectomized rats]. The effect of growth hormone on the DNA content in the nuclei of the thymus, spleen and the lymph node lymphocytes was studied by means of cytophotometry. In hypophysectomized rats the growth hormone increased the DNA content in the nuclei of the middle lymphocytes of these organs without altering its amount in the small lymphocytes. Thymus lymphocytes were the most sensitive to the hormone action. The DNA content in the nuclei of these cells increased as soon as one hour after the administration of the hormone; in 4 hours it reached the maximum. Other hormones with an anabolic effect (insulin, thyroxin, testosterone), induced no elevation of DNA in the thymocyte nuclei at that period of time. A conclusion was drawn on the high tropicity of the growth hormone to the cells of the lymphoid organs and particularly to the thymocytes (middle lymphocytes of the thymus).


E1Lymphocytopenia in pseudo-lupus-erythmetaosus syndrome. Seven female patients with pseudo-lupus erythematosus (LE)-syndrome had markedly reduced lymphocyte counts in their peripheral blood during the active phase of the disease. One patient, we were able to study during the active phase of her disease, had a diminuation of spontaneous rosettes-forming (T-)lymphocytes, using neuraminidase-treated sheep red blood cells for the test. In this case the percentage of surface-immunoglobulin-bearing (B-)lymphocytes determined by an indirect immunofluorescence technique was augmented. In comparison with 20 normal controls 6 other patients did not show any alterations in the relation of B- and T-lymphocytes in the peripheral blood. 5 patients had circulating lymphocytotoxic antibodies in their serum. A specificity of these antibodies for T-lymphocytes could not be realized.


Lysosomal acid phosphatase: difference between normal and chronic lymphocytic leukaemia T and B lymphocytes. Lysosomal acid phosphatase was assayed in homogenates of isolated normal and B cell type chronic lymphocytic leukaemia (B-CLL) T and B lymphocytes by biochemical means. Unlike the results of cytochemical studies reported in the literature enzyme activity was considerably higher in normal B lymphocytes than in corresponding T cells. This finding offers the possibility to use acid phosphatase as a marker for normal B lymphocytes. The diminution of acid phosphatase in unseparated B-CLL lymphocytes depends predominantly upon a loss of enzyme activity in the B cell fraction indicating an intrinsic abnormality of these neoplastic lymphocytes.


Toxicity of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin in larval and adult forms of Rana catesbeiana. Varying doses of TCDD ranging from 25 to 1000 mug/kg were administered to the larval and adult forms of the American bullfrog, Rana catesbeiana. Doses of TCDD as high as 1 mg/kg failed to have any significant effect upon survival or completion of metamorphosis in tadpole and doses of up to 500 mug/kg had no effect on survival of adult frogs. Histopathological examination of various tissues from the metamorphosed tadpoles and adult frogs failed to show any abnormalities.


[Recent data on the immunology of tumors. Mechanisms of escape of immunological control. Role of suppressor cells]. Cells in spleens from tumor bearing animals were found to inhibit in vitro reactivity of lymphocytes to a variety of stimulants. These suppressor cells inhibited the stimulation of normal lymphocytes by mitogens : P.H.A.-Con A-L.P.S. They were adherent cells, bore immunoglobulins at their surface and did not bear the 0 marker. They were also demonstrated in T deprived tumor bearing animals. They might be B cells, or, more probably, macrophages. Other activities that are inhibited by the suppressor cells are: -reactivity to allogenic cells in the mixed lymphocyte culture, -in vitro generation of secondary anti tumor cytotoxic effector cells, -macrophage migration inhibition in the presence of immune lymphocytes and tumor extracts, -reactivity against syngeneic tumor cells or tumor extracts. Suppressor cells may play a role in the general immunodepression of tumor bearing hosts, and in the inability of tumor bearing hosts to reject the tumor. However, the biological role of these non T suppressor cells is not clear, as they also inhibit tumor cell growth, and in vivo experiments favour suppressor cells of thymic origin.


Effects of haemorrhage upon surgical operations. The complications of emergency surgery for acute upper gastro-intestinal haemorrhage in 95 patients were compared with those of surgery for non-bleeding benign peptic ulceration in 380 patients. There was a significantly higher number of senior surgeons performing emergency surgery for haemorrhage. There was a significantly higher mortality (10-5 %), wound dehiscence rate (12-6 %) and wound complication rate with re-bleeding (33-7 %) in the post-haemorrhage patients compared with the non-bleeding group (1-3, 1-8 and 11-6 % respectively). There was no significant difference in the incidence of chest infection in the two groups. Mortality and morbidity after haemorrhage were correlated directly with the amount of blood transfused before surgery. Rats were used to study the effect of the removal of 13 % of the blood volume, and its restoration after varying time intervals, upon subsequent wound healing. Abdominal wounds were tested at 7 days for breaking and bursting strength. There was no difference between the wound strength of the control animals and animals which had been bled for 4 minutes before wounding. A significant reduction of wound strength occurred in animals which had been bled for 30-60 minutes before wounding. Prolonged blood loss was associated with deficient wound healing even if blood loss was restored before the wounds were made. Stored blood may be deficient in a factor which is necessary for normal wound healing.


Multidisciplinary treatment for macrometastatic osteogenic sarcoma. Using a co-ordinated multidisciplinary approach with surgery, radiation therapy, and chemotherapy, 14 out of 21 patients with metastases from osteogenic sarcoma were rendered free of disease for over two to over 18 months. Most patients had pulmonary metastases, two had bony metastases, and one had metastases in the iliac nodes. As part of this multidisciplinary approach weekly high-dose methotrexate was given and caused tumour regression in seven out of 15 patients. After all clinical evidence of disease had been removed high-dose methotrexate was administered every two to three weeks as maintenance treatment. To assess the efficacy of treatment the results were compared with those in a historical control group of 82 consecutive patients who developed pulmonary or other metastases. The results in the study group were significantly better. This experience may be similar to that in Wilms's tumour, where actinomycin D has increased the cure rate when administered as adjuvant therapy after treatment of localised or overt metastatic disease.


Surface morphology of the bullfrog amphibian papilla. The bullfrog amphibian papilla, which has been identified as the peripheral source of two of the three types of auditory axon in that animal, is shown to have a continual distribution of receptor types based on surface topography, but a dichotomy of types based on the adjacent tectorium and its apparent mechanical linkage to the receptors and their supporting cells and a second dichotomy based on receptor polarization patterns. Each dichotomy divides the receptors into two approximately equal populations and thus might correspond to the previously observed division of primary axons into two frequency-response types.


Tonic inhibitory influence of a supraspinal monoaminergic system on recurrent inhibition of an extensor monosynaptic reflex. Recurrent inhibition of the extensor (quadriceps) monosynaptic reflex (MSR) was antagonized by a 5-hydroxytryptamine (5-HT) precursor, 5-hydroxytryptophan (5-HTP, 75 mg/kg), and a specific 5-HT neuronal uptake blocker, fluoxetine-HC1 (Lilly 110140, 0.25-6 mg/kg), in unanaesthetized decerebrate cats. This inhibition of the flexor (posterior biceps-semitendinosus) MSR was not altered by fluoxetine. Cyproheptadine-HC1 (5 mg/kg) partially reversed the above blocking actions of 5-HTP and fluoxetine and a thoracic "cold block", which eliminates supraspinal inputs to the caudal spinal cord, also eliminated the blockade by fluoxetine on recurrent inhibition. Cyproheptadine (2.5-5 mg/kg) or phenoxybenzamine-HC1 (2.5-5 mg/kg), administered alone, enhanced recurrent inhibition of the extensor but not of the flexor MSR. Since a "cold block" increased recurrent inhibition of the extensor reflex in control animals but failed to alter the inhibition in animals pretreated with either DL-p-chlorophenylalanine (300 mg/kg i.p. for 2 consecutive days) or DL-a-methyl-p-tyrosine methyl ester-HC1 (125 mg/kg i.p. 16 and 4 h prior to experiment), the monoaminergic system would appear to be tonically active. In addition the neuronal uptake blocker, imipramine-HC1 (0.125-4 mg/kg), was more potent in antagonizing recurrent inhibition when injected intra-arterially to the spinal cord than when administered intra-arterially to the brain stem or intravenously, indicating that this agent acts in the spinal cord to block the inhibition. These results support our previous proposal (ref. 18) that a supraspinal system involving 5-HT and noradrenaline antagonizes recurrent inhibition of the quadriceps MSR. This monoaminergic system is tonically active with the 5-HT nerve terminals located in the spinal cord.


Evidence for an ascending inhibitory histaminergic pathway to the cerebral cortex. Previous observations from our laboratory indicate that metiamide is a specific histamine antagonist in rat cerebral cortex. In view of the recent finding that histamine levels and L-histidine decarboxylase (EC 4.1.1.22) activity in cerebral cortex decrease following disruption of the ipsilateral medial forebrain bundle (MFB), the present investigation was undertaken to examine whether iontophoretically applied metiamide antagonizes the inhibition of deep cerebral cortical neurones produced by stimulation of the MFB. In rats anaesthetized with a mixture of methoxyflurane, nitrous oxide and oxygen, stimulation of the ipsilateral MFB or the cortical surface with iontophoretically applied histamine depressed the firing of cortical neurones. Metiamide antagonized the histamine-induced depression and reduced the duration of inhibition produced by MFB stimulation. However, it did not alter the inhibition induced by the cortical surface stimulation. These results indicate that a histaminergic pathway ascending through the MFB may inhibit rat cerebral cortical neurones.


Royal College Lecture, 1976. Preoperative left ventricular ejection fraction and survival after coronary artery surgery. A preoperative ejection fraction (EF) of less than 0.30 slightly increases the immediate risk of myocardial revascularization. This risk can be greatly reduced by better myocardial protection and complete revascularization of the coronary lesions during surgery. Poor ventricular function, however, greatly influences the patient's long-term survival, especially when the EF is less than 0.30. In patients with coronary artery disease, in whom there are clinical and angiographic indications of an aortocoronary shunt and the EF, when measured in the right anterior oblique plane, is equal to or greater than 0.30, surgery may be performed with an acceptable surgical risk (3.9%) and satisfactory long-term (4- to 5-yr) survival (85%). When the EF is less than 0.30 it is necessary (before refusing operation) to conduct additional studies of venticular function such as biplane ventriculography, venticulography following the administration of nitroglycerin, epinephrine or after an artificially induced extrasystole. Isotope studies may also be considered, as they can reveal the presence of viable myocardial cells in the hypo- or akinetic segments.


A case of T-cell lymphoma with convoluted lymphocytes. A case of T-cell lymphoma, as defined by immunologic studies of lymph node, peripheral blood, and cultured cells, is presented. Convoluted lymphocytes were noted in the original lymph node biopsy, in cerebral spinal fluid preparations and terminally, in the peripheral blood. The prominent neuologic abnormalities representing both central and peripheral nervous system involvement were atypical. Other features included skin and testicular infiltration, leukemic transformation, and refractoriness to therapy. A somewhat similar clinical picture has been reported in other patients with diffuse, poorly differentiated lymphocytic lymphomas, some of which have proven to have a T-cell origin. T-cell lymphoma may represent a distinct clinical entity that calls for modifications of our traditional therapeutic approaches.


Sinus histiocytosis with massive lymphadenopathy and spinal epidural involvement: a case report and review of the literature. A case of "sinus histiocytosis with massive lymphoadenopathy" (SHML) in which spinal epidural involvement caused paraplegia is described. The literature pertaining to this newly recognized entity is reviewed; this review indicates that the process is not necessarily restricted to the lymph nodes and may be progressive in nature. The case we report is the first with histologically proved bone involvement.


Serum alpha1-antitrypsin in patients with lung cancer or abnormal sputum cytology. Serum alpha1-antitrypsin Pi types and trypsin inhibitory capacity (TIC) were measured in 72 patients with lung cancer and in 196 patients with abnormal sputum cytology but no clinical evidence of lung cancer to determine if a genetic deficiency of alpha1-antitrypsin (AAT) predisposes to lung cancer. The distributions of Pi types in these two groups of patients and healthy adults are similar. Serum TIC and AAT concentrations are elevated in lung cancer patients. However, patients with abnormal sputum cytology and no clinical lung cancer have normal levels of serum TIC and AAT. A genetic deficiency of AAT probably does not produce a state of increased susceptibility to the carcinogenic effects of respiratory carcinogens such as tobacco smoke.


Comparison of multiple in vivo and in vitro parameters in untreated patients with Hodgkin's disease. Multiple in vivo and in vitro immune parameters were used to examine 52 untreated patients with Hodgkin's disease in all stages. A significant number (p less than 0.01) of patients in all stages demonstrated abnormalities in DNCB sensitization, peripheral blood lymphocyte response to phytohemagglutination, absolute lymphocyte count, absolute number of T cells (as measured by spontaneous rosette formation with sheep erythrocytes), and absolute number of B cells (as measured by immunofluorescence with polyvalent antiserum). The number of T and B cells fell progressively with each stage, but the proportion of T to B cells remained constant. Cutaneous anergy was found in STAGES III and IV. Depressed circulating immunoglobulins were found in a few patients in all stages. Neither the total lymphocyte number nor the number of T and B cells correlated with the measures of lymphocyte function (skin test reactivity, DNCB sensitization, mitogen response, or immunoglobulin levels). This study suggests that selective abnormalities in the immune system exist even in early Hodgkin's disease, involving the absolute number of circulating T and B lymphocytes and T-lymphocyte function. The study fails, however, to define a consistent pattern of immune defects as characteristic of Hodgkin's Disease.


Cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma. A comparison of the detailed features and natural history of 12 patients with "Sézary Syndrome" with those in patients with classical "mycosis fungoides" has demonstrated that, with the exception of a leukemic phase in the former, the two syndromes are indistinguishable. Both disorders result from the proliferation of malignant thymus-derived lymphocytes with progressive involvement of skin, lymph nodes, and visceral organs; actual transition between these two syndromes have been documented. "Sézary Syndrome" and "mycosis fungoides" appear to represent variant clinical expressions of the same disease process. It is proposed that the present confusing and archaic terminology should be discarded and that the designation "cutaneous T-cell lymphoma, with or without leukemic phase" should be used in all future descriptions of this disorder.


Radiation-related myocardial injury. Management of two cases. Pericardial effusion and trifascicular block developed 5 years following mediastinal irradiation for Hodgkin's disease in a 19-year-old patient. Another 24-year-old patients had an acute myocardial infarction followed by severe angina pectoris 5 years following mediastinal irradiation for the same disease. A pericardial window and a permanent demand pacemaker were used in the first case; an aorto-coronary vein grafting was utilized in the second patient. Both patients responded to treatment and are well. Five other previously reported cases of myocardial injury that occurred 2 months to 8 years following mediastinal irradiation in young patients were reviewed. To our knowledge, successful surgical treatment of this disease entity has not been reported before. Close, long-term follow-up of patients who have received mediastinal irradiation should be helpful in the early recognition and successful management of these serious cardiac complications. The systematic clinical and radiographic surveilance of these patients should be supplemented by a routine 12-lead electrocardiogram.


Hairy cell leukemia. An immunologic and ultrastructural study. A case of hairy cell leukemia in a 39-year-old man is reported. Hairy cells from the peripheral blood, spleen, and bone marrow had lambda-type immunoglobulin on their surfaces; those from the peripheral blood and bone marrow also had IgD on their cell membranes. Frozen sections of spleen reacted with IgGEA, but not IgMEA or IgMEAC markers. Transmission electron microscopy revealed ribosome-lamella complexes in cells from the spleen, but not the peripheral blood. Scanning electron microscopy demonstrated a spectrum of cell surface morphology with many cells characterized by ridges and ruffles. The significance of these findings is considered and it is suggested that the hairy cell is a B lymphocyte.


Nodular malignant lymphoma and amyloidosis. A case report. A case of long-standing, nodular malignant lymphoma of lymphocytic type associated with nephrotic syndrome and systemic amyloidosis is presented. Review of literature revealed only six previously reported cases of systemic amyloidosis complicating non-Hodgkin's lymphomas. Recent studies have revealed that all of the nodular lymphomas are B-lymphocyte malignancies; that nodular lymphomas have high incidence (46-64%) of abnormality of intracellular immunoglobulin synthesis; that abnormality of serum immunoglobulin in such patients in uncommon (0-8%); and that at least one type of amyloid fibrils is made up of immunoglobulin light chains. These findings would suggest that there is an etiologic relationship between nodular lymphoma and systemic amyloidosis.


Convalescence following coronary surgery: a group experience. The patient who has heart surgery and returns home will experience many problems in adjusting to a modified lifestyle. Successful rehabilitation depends on many factors-the knowledge the patient has about his condition, his own motivation and the support he receives from family and friends. If he has received good teaching in the hospital, his task will be much easier. But is in-hospital teaching enough? Current nursing research suggests that patients are more receptive to health teaching after they have returned home and benefit from sharing experiences with a group. The author describes the results of an investigation into the concerns of convalescent coronary patients and their wives and tells how group sessions helped ease their transition from hospital to a productive lifestyle.


Methotrexate (NSC-740) with citrovorum factor (NSC-3590) rescue, alone and in combination with cyclophosphamide (NSC-26271), in ovarian cancer. In a randomized study, 35 patients with advanced-stage epithelial ovarian cancers with progressive disease after prior single alkylating agent or combination-agent chemotherapy were treated with either intermediate high-dose methotrexate-citrovorum factor rescue alone or methotrexate-citrovorum factor rescue plus cyclophosphamide. Objective responses to both "second-line" chemotherapeutic regimens were observed. The objective response rate of 43% observed with the methotrexate-citrovorum factor plus cyclophosphamide treatment was superior to that achieved with methotrexate-citrovorum factor given alone. This combination of agents is the most effective second-line chemotherapeutic regimen for ovarian cancer that we have yet tested and we are therefore optimistic about its possibilities as first-line therapy. After early dosage modifications, serious toxic side effects were rare in this group of patients who had had extensive prior therapy.


Experimental chemotherapy with 5-arylpyrimidine antifolates: preliminary studies on toxicity and responsiveness of sarcoma 180 to DDMP (NSC-19494) and DDMP with citrovorum factor (NSC-3590). The 5-arylpyrimidine antifolate DDMP showed appreciable therapeutic activity against an ascitic form of Sarcoma 180 in BD2F1 mice. Antitumor effects were highly schedule and dose dependent at a limited number of doses within the range of 8--40 mg/kg. The best results (increased lifespan = 112%) were obtained with two doses of DDMP at 40 mg/kg given 4 days apart. The incorporation of citrovorum factor rescue in dose schedules with DDMP appeared to improve the therapeutic index. In multiple-dose schedules with citrovorum factor allowing an average of eight doses of DDMP at a maximum level of 16 mg/kg, increases in median lifespan were greater than 158% with a number of long-term survivors.


Innervation of skin glands in the frog.

Innervation of skin glands in the frog. A comparative study was undertaken on the innervation of mucous and granular glands in frog skin. Results obtained by the Falck-Hillarp fluorescence technique and cholinesterase staining indicated that both types of glands receive exclusively adrenergic innervation. Electron microscopy was used to investigate the innervation pattern at the ultrastructural level. The distribution of nerve terminals was found to differ in the two types of glands. In the mucous gland, terminals were found at a distance of about 0.5 mum from the basement membrane but never within the gland parenchyma. In the granular gland, the terminals were located between smooth muscle cells and also in direct contact with the secretory epithelium but never outside the basement membrane.


Apical secretion from taste bud and other epithelial cells in amphibians. Taste buds of the axolotl, Ambystoma mexicanum, contain cells, previously undescribed in this species, which have a long apical process, and are similar to the Type III cells of mammalian taste buds, and to the gustatory cells in fish. In the supporting cells, there is evidence of periodic decapitation, in addition to secretion by exocytosis. Bilaminar fragments, which are leaf-shaped bodies formed of two dense laminae separated by a lucent gap, protrude from the apical microvilli of the supporting cells and are found detached in the extracellular secreted layer. Their form and dimensions suggest that they represent secreted lipo-protein material. Similar bilaminar fragments have been seen, in much smaller numbers, on some other epithelial cells in amphibians, and in fish. A unique case, in which rough endoplasmic reticulum was found in the extracellular layer of the axolotl oral epithelium, is reported; it had apparently been ejected from the cell. It is suggested that the axolotl produces a copious secretion at the taste bud pore, in order to wash the surface, and that the bilaminar fragments represent material aiding this cleansing process. The condition in the axolotl is compared with that in some other species, particularly Rana temporaria.


Permeability of the amphibian pars intermedia to peroxidase injected intravascularly. To study the penetration of protein from the blood into and through the pars intermedia of anurans, the electron-dense tracer, horseradish peroxidase (HRP), was injected into the vascular system of the frog, Rana pipiens. Pinocytotic vesicles were seen along plasma membranes of the stellate cells abutting the pericapillary spaces between the pars intermedia and pars nervosa. The HRP was seen within both the pericapillary spaces and these pinocytotic vesicles. In addition, the HRP was very prominent in the extracellular spaces between adjacent stellate and/or MSH cells and around nerve endings and thus, appeared to move from the vascular spaces and into the interior of the pars intermedia. Therefore, the poorly vascularized pars intermedia may have such a route for transfer of materials throughout the gland.


The inhibition by DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) of hnRNA and mRNA production in HeLa cells. 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB; 75 muM) inhibited only 60-75% of nuclear heterogeneous RNA (hnRNA) synthesis in HeLa cells, while the appearance of labeled cytoplasmic poly(A)-containing messenger RNA (mRNA) was reduced by approximately 95%. DRB-sensitive and resistant transcripts spanned the entire size range of hnRNA molecules. The relative poly(A) content of DRB-resistant hnRNA molecules was the same as that of normal hnRNA. In contrast to the effects of 3'deoxyadenosine, DRB appeared to inhibit the initiation of hnRNA chains, but did not directly interfere with labeling of poly(A). We present an interpretation of these results and propose how the results might be used to gain more information about nuclear RNA metabolism.


The relation between acute persisting spinal paralysis and poliomyelitis vaccine (oral): results of a WHO enquiry. The present report presents the findings in 8 countries at the end of the first 5 years of an international investigation into the possible relationship between acute persisting spinal paralysis and the use of oral poliomyelitis vaccine.The most striking finding was the high association with type 3 virus in the recipient cases and with type 2 virus in the "contacts" and "possible contacts". Most of the cases in the recipient groups occurred in children under 5 years of age in all countries, but in the "contact" groups in the countries in which vaccination is offered through the year, many of the cases occurred in the non-immune parents of recently vaccinated infants.There were marked differences among countries, and it was not possible to pinpoint a single factor as the sole cause. However, the quality of the vaccine clearly played an important role. For some time, and certainly at the beginning of this enquiry, some of the countries were using vaccine from the same source without continuous external control and were using seed viruses at high passage levels. The situation changed during the enquiry and the incidence of paralytic cases decreased. The enquiry will be continued and particular efforts will be made to establish the cause of the associated paralysis. The findings of the enquiry confirm that oral Sabin poliomyelitis vaccines are among the safest vaccines in use today.


Trial of a reduced dose of measles vaccine in Nigerian children. To evaluate the effectiveness of measles vaccine in reduced dosage, Schwarz live, further attenuated measles virus vaccine was given in various doses by jet injector to 967 seronegative children aged 7-30 months in rural villages in the Northwest State of Nigeria. For children over 12 months of age, reducing vaccine virus dosage by 40%, 60%, or 80% led to progressive and statistically significant reductions in the seroconversion rates from 89% in children receiving the full dose to a minimum value of 46%. Reducing the volume of the inoculum below the standard of 0.5 ml resulted in a further reduction of seroconversion rates at each antigen dose level. Seroconversion rates in all dosage groups were lower for children below 12 months of age. These data suggest that dose reduction would not be a satisfactory economy measure in measles vaccination campaigns.


Kaeng Khoi virus from naturally infected bedbugs (cimicidae) and immature free-tailed bats. Kaeng Khoi virus was recovered from bedbugs (Stricticimex parvus and Cimex insuetus) and from suckling wrinkle-lipped bats (Tadarida plicata) collected in central Thailand. The data implicate bedbugs as possible vectors of this virus.


Effect of cysteine on the hepatic toxicity and antischistosomal activity of antimonyl potassium tartrate. Cysteine produced a significant and progressive reduction in the toxicity of antimonyl potassium tartrate (APT) when the two substances were injected into mice and rabbits in ratios of APT to cysteine ranging from 1:1 to 1:3. The reduction in toxicity was highest with the 1:3 ratio. However, the combination of the two substances, especially in the ratio of 1:3, appreciably reduced the antischistosomal activity of APT both in vivo and in vitro.


The suppression, by Helisoma duryi, of the cercarial production of Schistosoma mansoni-infected Biomphalaria pfeifferi. Biological control of the intermediate hosts of Schistosoma mansoni and S. haematobium by means of a competitor snail, Helisoma duryi, has been suggested. In the present laboratory study, the influence of H. duryi on the relationship between the parasite and the intermediate host was investigated. The results indicated that H. duryi behaves as a "decoy" if it is present when Biomphalaria pfeifferi is exposed to the miracidia of S. mansoni, and that the continued presence of H. duryi in the aquarium after B. pfeifferi has been exposed greatly reduces cercarial production. When these two species were present in equal numbers, cercarial production was reduced by 95.9% in comparison with a control group.


Parasite cultivation in relation to research on the chemotherapy of malaria. Attempts to develop techniques for the continuous in vitro cultivation of the malaria parasite have not yet proved successful. It has not been possible to obtain the complete sporogonic development of the parasite in vitro although some progress was made with Plasmodium relictum and P. berghei. Exoerythrocytic stages of P. gallinaceum have been successfully cultivated in vitro in tissue explants and those of P. fallax have been grown in turkey primary embryo tissue cells. With the recent development of mammalian liver cell lines, prospects for the in vitro cultivation of exoerythrocytic stages of mammalian plasmodia are greatly improved. While it is still not possible to cultivate erythrocytic stages of plasmodia serially in vitro some species have been successfully grown through one asexual cycle. This progress has led to a number of applications of parasite cultivation to chemotherapeutic studies, to the testing of new antimalarial drugs, and especially to the testing of the susceptibility of P. falciparum to chloroquine. Cultivation technique is greatly improved by an appropriate choice of culture media. The addition of fresh red cells to the subculture system permits relatively high rates of invasion and multiplication of the parasite to be obtained. As well as its application in the screening and evaluation of antimalarial compounds, the in vitro cultivation technique is also very suitable for studying the entry mechanism of the parasite into red blood cells.


Antibody persistence after surgical treatment of echinococcosis. Studies on the persistence and levels of antibodies in 280 patients at different intervals following surgery for echinococcosis are described. Post-operative antibody levels were investigated by means of four immunodiagnostic methods, namely, the complement fixation, latex agglutination, indirect haemagglutination, and intradermal tests. After surgical removal of the cysts the tests became negative in some patients, whereas in others they remained positive for many years. As the post-operative period increased, the percentage of positive results fell and this fall was faster in lung echinococcosis than in liver echinococcosis. The titres obtained with the serological tests decreased at the same rate as the percentage of positive results, but the intradermal test remained positive, with an unchanged titre, for many years. In the case of secondary echinococcosis, medium and high titres predominated in all the tests. These immunological investigations during the post-operative period make it possible to evaluate the results of surgery and, to some extent, to clarify the prognosis.


Experimental chemotherapy in leprosy.

Experimental chemotherapy in leprosy. The Memorandum reviews the considerable progress that has been made in research on the chemotherapy of leprosy during the last 10-15 years, as a result of which it is now possible to study the same topics in leprosy as are studied in other bacterial diseases. Thus drugs have been screened in mice for their activity against Mycobacterium leprae. Those that have been found to have the greatest activity against M. leprae at acceptable dosages-dapsone, rifampicin, and clofazimine-have been characterized in terms of the minimal effective dosage and rate of bacterial kill. Similarly, their pharmacokinetics in man and in certain animals have been defined. The theoretical basis for drug trials in leprosy patients is discussed in terms of the number of viable and the number of dead M. leprae that remain at various stages of therapy.


Tuberculin sensitivity in guinea-pigs after vaccination with varying doses of BCG of 12 different strains. In several previously reported studies a number of BCG strains, including those most widely used in vaccine production, were ranked according to their in vivo activity in various experimental models in rodents and to the local and allergic response that they provoked in children. In this report, 12 strains are ranked in terms of tuberculin conversion in guinea-pigs according to the minimum sensitizing dose. For 10 of these strains, this minimum dose is very low, ranging from 5 to 50 culturable particles. Thus the traditional practice of tuberculin-testing guinea-pigs that have been vaccinated with a full human dose of BCG (of the order of one million culturable particles) has such a low discriminating power that it is useless as a routine test for currently used vaccines. The ranking obtained in this model was largely but not completely in accordance with similar rankings in other models. The Tokyo strain and, to some extent, the London strain ranked comparatively lower than they do in children. The pronounced lack of virulence of the Prague strain was confirmed.


Diagnosis of rheumatism by means of universal criteria, obtained by the cybernetic method. With a view to establishing standardized criteria for the diagnosis of rheumatism suitable for widespread use in polyclinics and in large-scale epidemiological investigations, 3000 adults and children with rheumatism or one of seven similar diseases were subjected to multiple screening in eight centres in the USSR using a specially prepared standard card and standard methods. The information obtained was processed by cybernetic methods. Following determination of the sensitivity, specificity, and informational value of 486 signs of rheumatism, 68 of the most indicative signs were selected as criteria of rheumatism. These were included in the final table and weighted according to their indicational value both individually and in groups as syndromes. Using the table it is possible by simple calculation, without using a computer, to arrive at an objective evaluation of the reliability of the clinical diagnosis of rheumatism in patients with one of a group of eight similar diseases. The final diagnostic table was tested on 562 patients selected epidemiologically or from polyclinics or clinics and was shown to result in a high degree of diagnostic precision (higher than 95%).


Sudan: national health programme and primary health care, 1977/78-1983/84. As a follow-up to the national health programming process developed in 1975 in Sudan, a primary health care programme for the whole country was formulated with assistance from WHO. In this article the methods used in the programming and formulation are described and discussed. These methods ensured an intersectoral approach on which technical, cultural, socioeconomic, financial, and political considerations were based. Areas in the field of health and rural development requiring government and community action during the period 1977/78-1983/84 are identified. Details on the strategies for population coverage of rural and nomadic communities with primary health care are given. Fundamental to these strategies is community participation in the development of primary health care within community development as a whole.The guiding principles of these strategies are their technical, political, social and financial feasibility. The social relevance of the primary health care programme for the community and the developmental sectors is emphasized.


Epidemiological studies on onchocerciasis by means of a new field technique. A new membrane filter concentration technique for the detection and quantification of Onchocerca volvulus microfilariae in skin snips was compared for sensitivity and efficiency with a widely used "standard" technique. A field study was carried out in five villages in an onchocerciasis focus north-east of the town of Sokodé, Mô river valley, Togo. Use of the new technique resulted in a substantial rise in the observed prevalence and density of microfilariae.


Socioeconomic scoring in an urban area of a developing country. A group of variables that might define "life-style" was selected and a questionnaire based on these was distributed to the families of 2350 schoolchildren in Accra, Ghana to determine the presence or absence of these variables. Analysis of the replies revealed a set of answers that formed a related group. A scoring system was developed in which rarer attributes were weighted, and the community was thus graded by socioeconomic status on a ten-point scale. Principles for developing questionnaires applicable to other types of community were defined.


A streptomycin-sensitive revertant of a streptomycin-dependent strain of Vibrio cholerae. A study was made of a streptomycin-sensitive revertant of a streptomycin-dependent strain of V. cholerae. The revertant, designated as strain KB599, appears to be avirulent in animal experimental models. However, no evidence of multiplication was found in infant mice.


Determination of improved myocardial perfusion after aortocoronary bypass surgery by exercise rubidium-81 scintigraphy. Practical and noninvasive means are needed for evaluating efficacy of coronary bypass surgery (CBS) in improving blood flow (CBF) to ischemic myocardium in coronary patients. Revascularization was assessed in 15 patients by pre- and post-CBS rest and exercise rubidium-81 myocardial images with a scintillation camera equipped with pinhole collimator and high-energy shield. Ischemic areas were detected by decreased 81Rb activity after exercise compared to rest. Before CBS all patients had exercise angina (EA), positive treadmill ECG (TECG), and abnormal exercise 81Rb scans. After CBS all 15 patients had increased physical activity before angina or completion of treadmill exercise with increased heart rate-blood pressure product (HRBP) (+ 63 +/- 3.2 X 10(2) bpm - mm Hg) in 14 of 15 patients indicating increased CBF; four had positive TECG, and five had EA. The increased HRBP in 14 patients was associated with improved post-CBS exercise 81Rb scans: six had normal patterns while nine were improved with less ischemic patterns. Further, lack of angina and increased exercise tolerance correlated closely with increased 81Rb myocardial perfusion. Thus pre- and postoperative rest and exercise 81Rb scintigraphy gives an accurate, noninvasive, objective approach for evaluation of CBF following CBS and demonstrates the usefulness of this revascularization procedure in coronary patients.


Long-term follow-up of patients with coronary artery bypass grafts. A follow-up study of 1532 patients who had coronary artery bypass grafts from 1969 through 1974 revealed that the 5-year survival rate was substantially better than that recorded in previously published series of patients with similar disease demonstrated angiographically who did not undergo operation. Within this group of operated patients, those who had complete myocardial revascularization (i.e., three grafts for those with three-vessel disease) experienced a significantly better long-term prognosis than those who had fewer grafts than the number of vessels obstructed. The mortality curve in the completely revascularized patients was very similar to that of the general population of the United States, corrected to correspond to this patient sample in age and sex.


Refractory angina pectoris: follow-up after intraaortic balloon pumping and surgery. Ffity-five patients with recurrent severe angina pectoris at rest that was resistant to medical therapy were treated with intraaortic balloon pumping (IABP), angiography, and vein bypass surgery. There were 25 patients with typical angina with ST depression during pain, 12 with Prinzmetal's angina, and 18 patients with angina in the early recovery phase following "transmural" myocardial infarction. The severity and frequency of ischemic attacks were documented with hemodynamic and continuous electrocardiographic monitoring. A marked reduction in both frequency and intensity of attacks was produced by IABP. Temporary cessation of IABP resulted in rapid recurrence of angina in 40% of patients. All underwent selective coronary angiography and revascularization surgery. The overall mortality was 5.5% and the incidence of intraoperative myocardial infarction was under 2%. Follow-up evaluation after an average of 18 months has shown no late deaths and sustained clinical improvement.


Patency of internal mammary-coronary grafts. Patency of internal mammary artery (IMA) coronary grafts was evaluated in 150 patients having an early (20 days) and late (13 months) postoperative angiogram. Early and late failure for 76 right IMA grafts was 3 and 5 respectively and for 139 left IMA grafts 7 and 7 an overall IMA patency of 95% and 90%. The IMA and coronary internal diameter did not relate to graft closure. Right IMA free flow did not correlate with graft closure. Free flow for thrombosed left IMA grafts (91 ml/min) was significantly (P less than 0.05) lower than for patent grafts (118 ml/min). Right IMA anastomotic flow of 55 ml/min was significantly (P less than 0.001) higher than occluded graft flow of 26 ml/min as was true for patent left IMA grafts (55 ml/min) and occluded grafts (43 ml/min) (P less than 0.025). Five of 215 IMA grafts had diffuse stenosis (greater than 50%). Saphenous vein coronary bypass was performed in 88 instances with an early patency of 89% (79/88) and a late patency of 88% (78/88). Only one of 38 vein grafts to the right coronary artery failed whereas eight of 44 grafts to the circumflex artery occluded. Experience was associated with increased late IMA patency from 81% (57/70), to 89% (;8/76), to 99% (68/69) in each successive group of 50 patients. Currently, the left IMA is routinely used for the left anterior descending artery and the right IMA is rarely used.


Balloon counterpulsation following surgery for ischemic heart disease. Intraaortic balloon counterpulsation (IABC) was used in 40 patients who developed left ventricular pump failure following surgery for ischemic heart disease. The IABC was inserted in the operating room in 32 patients, and within 36 hours of surgery in eight patients. Four patients could not be weaned from cardiopulmonary bypass and died in the operating room. Of the other 36 patients, eight died while on IABC. Twenty-eight patients (70%) were successfully weaned from IABC, although six died later in hospital. Twenty-two patients (55%) survived hospitalization. No late deaths have occurred at 5-33 months of follow-up (mean 16-4 months). Twenty (91%) of 22 survivors are Class I or II at time of this report. Postoperative pump failure occurs because of perioperative acute myocardial infarction and/or major preoperative left ventricular dysfunction. Patients with perioperative infarction who have no prior left ventricular dysfunction have a significantly lower mortality (14%) than do those patients with preoperative left ventricular dysfunction who have subsequent acute perioperative infarction (mortality 67%) P less than 0.05.


Survey of amniocentesis for fetal sex determination in hemophilia carriers. A study was designed to determine whether there is an increased risk of complications when amniocentesis for fetal sex determination is performed on hemophilia carriers. Questionnaires were sent to 112 medical centers providing this service in the United States, and to 19 outside the United States. Responses were received from 76% of the centers in the United States. Data on 11,819 taps were obtained. Only 75 taps (0.64%) were performed for the indication of hemophilia. The frequency of fetal deaths in the general sample (1.84%) was not significantly different from that in the subsample of hemophilia carriers (1.33%). The results of this survey correspond very closely to data from a National Registry on amniocentesis for various indicaions in such variables as the number of taps needed for diagnosis, color of the fluid obtained, and number of dry taps. Carrier women who had bleeding problems during the monitored pregnancy are described. The problems might have been related to the amniocentesis in three women. It is calculated that only 2-4% of hemophilia carrier women who might have amniocentesis are utilizing the service.


T, B and K cells in autoimmune thyroid disease. The K-cell cytotoxic activity of peripheral blood lymphoid cells from 104 patients with autoimmune thyroid disease and from age and sex matched control subjects was measured using chicken erythrocytes as target cells. Patients with Hashimoto thyroiditis,primary hypothyroidism and thyrotoxicosis who were either newly diagnosed and untreated or had received therapy for less than or equal to 1 year showed a significant increase in K-cell cytotoxic activity. Patients who had received treatment for greater than 1 year and less than or equal to 5 years showed no such comparable increase in cytotoxic activity. Within the group of patients with untreated thyrotoxicosis it was found that K-cell cytotoxic activity was related to both goitre size and serum antibody titre. Thus patients with little or no goitre showed a highly significant elevation of cytotoxic activity whereas patients with moderate to large goitres gave values within the normal range. Similarly patients with no detectable serum thyroid autoantibodies showed high K-cell activity while patients with positive antibody titres did not. It was also shown that neither the absolute number nor the proportion of circulating T and B lymphocytes in patients with autoimmune thyroid disease as assessed by the sheep red cell rosette method and by indirect immunofluorescence was significantly different from that observed in the normal control population. No correlation was found between peripheral blood K-cell cytotoxic activity and the percentage of circulating null cells, i.e. 100-(percentage T + percentage B) in either patients or control subjects.


Acute phase proteins and C9 in patients with Behcet's syndrome and aphthous ulcers. Estimation of the concentration of C9, C-reactive protein (CRP) and alpha1-antitrypsin in forty sera from patients with Behcet's syndrome and recurrent oral ulcers showed significantly increased amounts of C9 and CRP in Behcet's syndrome. The concentration of C9 was also significantly raised in recurrent oral ulceration, though to a lesser extent than in Behcet's syndrome. The assay C9 and CRP might be useful in the differential diagnosis of Behcet's syndrome, especially from recurrent oral ulcers. It is suggested that during epithelial inflammation in recurrent oral ulcers some of the acute phase proteins are increased and in some patients these may modulate the immunological mechanism in such a way as to induce a transition from focal oral ulceration to the multifocal Behcet's syndrome.


Receptors for Helix pomatia A haemagglutinin on leukaemic lymphocytes from patients with chronic lymphocytic leukaemia (CLL). Blood lymphocytes from thirteen patients with CLL were studied for surface-bound Ig (SIg), Fc receptors (EA rosettes), receptors for sheep erythrocytes (E rosettes) and receptors for Helix pomatia A haemagglutinin (HP), a carbohydrate-binding protein with specificity for N-acetyl-D-galactosamine and related sugars. Fluorescein-labelled HP binds to subpopulations of human peripheral blood lymphocytes (PBL) treated with neuraminidase. In normal peripheral blood, HP binds to the T-lymphocytes while the majority of the B cells bearing surface-bound immunoglobulin do not have receptors for HP. In untreated CLL, HP binds to 90-100 percent of the neuraminidase-treated PBL. Almost all of the SI-G-POSITIVE CELLS IN CLL patients also have receptors for HP. Two groups of patients were found: in one the total fraction of SIg+ cells was less than or equal to 50 percent and about 30 percent of these lost their Ig during incubation at 37 degrees C. No such loss of SIg was revealed in the remaining patients where total SIg+ fraction was approximately 70 percent. These patients usually had higher blood lymphocyte counts, probably reflecting a more advanced disease. CLL patients in remission with low numbers of leukaemic cells also had low numbers of blood lymphocytes carrying both SIg and HP-receptors. It is concluded that leukaemic cells carry both HP receptors and SIg. Testing of this combination therefore provides a valuable new tool for monitoring patients with CLL.


Peripheral blood lymphocyte populations in chronic liver disease. Mature T lymphocyte concentrations are reduced, null cell concentrations are increased, and Fc receptor bearing (B and K) lymphocyte concentrations are normal, in the peripheral blood of patients with chronic hepatocellular or cholestatic liver disease. Some null cells can be stimulated by either thymosin or levamisole to form rosettes with sheep erythrocytes. These changes are present in viral, alcohol associated and 'autoimmune' liver disease and are therefore probably secondary phenomena relating to liver damage.


Study of lymphocyte subpopulations in normal humans and patients with systemic lupus erythematosus by fractionation of peripheral blood lymphocytes on a discontinuous Ficoll gradient. Peripheral blood lymphocytes of thirty normal volunteers and fifty-two patients with systemic lupus erythematosus were fractionated using a discontinuous (5-30 percent) Ficoll gradient. Such fractionation permitted the isolation, identification of study of null cells, T cells and B cells. Patients with inactive SLE were found to have a cell distribution and responsiveness to PHA, Con A and Pokeweed mitogen (PWM) similar to controls. In contrast, patients with active SLE showed a significant decrease in T-cell fractions as well as a relative increase in null cells, a normal distribution of B cells, a marked reduction in responsiveness to Con A, a lesser reduction to PHA and only a minor reduction to PWM. With increasing disease activity, the number of null cells increased despite lymphopenia. Spontaneous lymphocyte transformation was observed in patients with SLE. This occurred predominantly in the fractions enriched in B cells and was observed both early (0-16 hr) and late (68-72 hr) in the lymphocyte cultures. The method of discontinuous Ficoll gradients is both versatile and reproducible with good correlations between isolated lymphoid subpopulations and disease activity.


Cell suppression in PPD-induced blast specific response of human peripheral blood lymphocytes. Secific stimulation of T-cells by PPD was inhibited by their autologous B cells. This inhibition was obtained with B cells separated either by depletion of E-RFC or by elution, with human IgG of lymphocytes bound to Sephadex beads coated with rabbit antibodies anti-human Fab fragments. The suppression was proportional to the number of B cells added to 10(6) T cells incubated with PPD and as previously reported was more marked in the case of B or T cells from BCG-vaccinated subjects with negative skin tests. The suppressive phenomenon required viable B cells and was inhibited by cycloheximide but was not altered by pretreatment of suppressor cells with actinomycin D or colchicine. It seems that B-suppressor cells interfere with recognition of PPD by T cells rather than with the proliferative phase of the specific blast response. Using various surface markers (i.e. Ig, C3 and Fc receptors) it was shown that the suppressor cells represent a subset of Ig-bearing B cells which do not carry Fc receptors.


Influence of dietary protein restriction on immune competence. II. Effect on lymphoid tissue. Weanling mice fed a 4 percent diet showed a generalized loss of lymphoid tissue which was greater than the loss of total body weight. This effect was greatest in the thymus greater than spleen greater than mesenteric lymph node. Cell loss was most pronounced during the 1st week on diets, then remained at stable levels for 3 weeks and showed a gradual rise thereafter. The effect was shown to be mediated partly by a cessation of growth in lymphoid organs due to the low protein intake and, secondly, an adrenal corticosteroid induced lympholysis which actually reduced cell numbers. Recirculating T cells and resident B cells were amongst the least affected cells whereas stem cells, non-migratory T cells and other reticuloendothelial cells were most depressed in numbers. At no stage was the germinal centre forming capacity of the mesenteric node lost although cell recruitment to antigenically stimulated nodes was diminished. During nutritional repletion the spleen, thymus and mesenteric node all showed different and characteristic regrowth. The spleen was most active initially and rapidly reconstituted haemopoietic cells and B cells. This was followed by the thymus which showed a delayed reinitiation of its normal growth kinetics which had been interrupted by the diet. The evidence suggested that full rehabilitation of the immune apparatus took place even after 2 months of nutritional deprivation.


Ampicillin and an ester in experimental Hemophilus influenzae meningitis. A new methoxymethyl ester of hetacillin is highly lipid-soluble, a property which was expected to enhance its penetration into the central nervous system (CNS). We compared the penetration of the ester and ampicillin into the cerebrospinal fluid (CSF) of normal rabbits and those with experimental Hemophilus influenzae meningitis. In normal rabbits treated by constant intravenous infusion, mean per cent penetration (see article) of the ester was four times as great as that of ampicillin (6.6 +/- 3.7% against 1.6 +/- 1.9%), and the difference in CSF drug levels attained was accentuated when bolus IV infusion was used. Drug concentration in brain tissue was three times as great in a rabbit treated with the ester (0.79 mug/gm against 0.26 mug/gm). In rabbits with meningitis, the ester again achieved higher CSF concentrations. Per cent penetration into CSF in infected rabbits was 23% for the ester and 13% for ampicillin. Bactericidal activity of the drugs was comparable; over 8 hr of treatment both drugs significantly reduced the CSF bacterial titers of infected animals. Our data demonstrated that the ester enters the CSF and CNS in higher concentration than ampicillin, with no loss in bactericidal activity.


Immunobiology of the gastrointestinal tract. The interplay between the gut and immune abnormality appears to be a logical extension of the thesis that secretory  IgA  is the major immunologic line of defense between the outside environment and the host. Thus immunologic deficiency, particularly of IgA and combined T- and B-lymphocyte abnormalites, profoundly influences gut integrity. Conversely, gut pathology is bound to interfere with immunologic function, so that both humoral and cellular immunity may be impaired. Finally, hypersensitivity phenomena in the gut, resulting in immune injury, may cause gastrointestinal disturbances. As better diagnostic tools have become available, more direct evidence of hypersensitivity immune injury has been described.


[Improved control of the pressure during use of the Sengstaken-Blakemore tube]. For the control of acute hemorrhage from esophageal varices by balloon tamponade a proper application of the Sengstaken-Blakemore tube is necessary to arrest bleeding and to minimize complications. A simple modification of the pressure measurement used up to now is described with other suitable applications. By this modified technique a correct pressure can be kept in the esophageal balloon spontaneously; its ease in handling in intensive care makes for better results in emergency management of balloon-tamponade in treatment of acute bleeding from esophageal varices.


Intestinal immunization with soluble bacterial antigens: the example of cholera toxoid. The studies described are aimed at a better understanding of the intestinal immunological system and its role in protection against enteric infection. The cellular kinetics of the intestinal immune response to cholera toxoid were studied in rats and the protection afforded by toxoid immunization was studied in dogs. Memory was demonstrated in the gut immune system. Plasma cells containing IgA antitoxin appeared in large numbers in gut lamina propria when intraduodenal boosting followed either intraperitoneal priming or prolonged oral priming, intraperitoneal priming being the most efficient. Immunization by the intraperitoneal route alone produced no response in small bowel lamina propria. Lamina propria plasma cells were derived from precursors in Peyer's patches or mesenteric lymph nodes which migrated through the thoracic duct and systemic circulation before homing to the gut. Dogs were immunized parenterally with cholera toxin or toxoid and challenged orally with Vibrio cholerae. Protection correlated closely with serum antitoxin titres and was usually brief. Passive intravenous immunization with IgG antitoxin was also protective. In contrast, subcutaneous priming followed by oral boosting yielded longer protection without elevated serum antitoxin titres. Antitoxin was detected in jejunal washings only briefly after local boosting. The mechanism by which protection is prolonged is unclear but its greater duration after parenteral priming and oral boosting emphasizes the importance of stimulating the gut immune mechanism in attempts to immunize against enteric bacterial infections. The parenteral-oral squence may be an effective means of immunizing the intestine with non-replicating protein antigens.


Regulation of glucose-6-phosphate dehydrogenase activity in uterine tissue in organ culture. An organ culture technique, employing a totally defined medium, was developed, in which the levels of glucose-6-P dehydrogenase (G6PD) activity in uterine tissue from estradiol-treated ovariectomized mature rats continued to increase in vitro for 18 h at a rate similar to that seen in vivo. Uterine G6PD levels did not increase in vitro in tissues from estrogen-deprived rats even if estradiol (10(-6)m) was added in vitro, but the administration of estradiol (5 mug/rat) in vivo for as little as 2 min permitted G6PD levels to increase by 0.03 units/uterus (from 0.075 to 0.10, units/uterus) after the 18 h incubation. The maximum increase of 0.08 units/uterus (from 0.147 to 0.230 units/uterus) was seen in uteri from rats which were given estradiol 12 h prior to sacrigice. Tissues from animals given estradiol for greater than 30 h exhibit a net decrease in G6PD levels under the in vitro conditions. The in vitro increase in G6PD activity is inhibited by the addition of either actinomycin D (5 mug/ml), cycloheximide (5 mug/ml), or cordycepin (150 mug/ml), or by the intrauterine injection of actinomycin D (10 mug/rat). Intrauterine administration of cycloheximide (100 mug/rat) inhibited the in vivo increase in enzyme activity; however, the enzyme levels increased after placement of uterine tissues from these animals into organ culture. The removal of cycloheximide, which was added at the beginning of incubation after the 12th h, restores the ability of the tissues to increase the G3PD activity, and this restoration is not blocked by the addition of actinomycin D, suggesting that the mRNA activity for uterine G6PD accumulated during in vitro inhibition of protein synthesis by cycloheximide. The in vitro increase in uterine G6PD is due to an increase in immunologically identifiable G6PD protein and this increase is due, at least in part, to an increase in the de novo synthesis of the enzyme, as measured by the incorporation of [14C]leucine into immunochemically isolated G6PD protein. These results suggest that once initiated in vivo by estradiol, the uterus is capable of continuing in vitro those events, including the synthesis of both RNA and protein, which result in an increased rate of synthesis of uterine G6PD.


Spontaneous rupture of colic-artery aneurysms: report of two cases. Two cases of spontaneous rupture of colicartery aneurysms are presented, one involving the left colic artery and the other the right colic artery, and the literature on abdominal apoplexy and visceral arterial aneurysms is reviewed. In view of the potential for life-threatening hemorrhage, it is urged that, whenever feasible, visceral arterial aneurysms be resected prophylactically when discovered by angiography or at celiotomy.


Long-term survival following aortocoronary artery bypass. Analysis of 4,522 consecutive patients. At the Texas Heart Institute, from October 1969 through December 1974 a consecutive series of 4,522 patients who underwent aortocoronary bypass procedures was analyzed. Our experience with this procedure over a 5-year period demonstrated a decreasing operative and long-term mortality. This included patients who had aortocoronary bypass alone or in combination with other procedures such as resection of a left ventricular aneurysm or aortic and mitral valve procedures. Actuarial follow-up during the 5 years revealed mortality to be approximately 2.5% per year. Current operative mortality is less than 3.5% regardless of the number of grafts implanted. The rate of late myocardial infarction was only 4% for the entire series. Coronary artery bypass can be safely performed with minimal mortality and increased long-term survival.


The intestinal mucosal lesions in shock. I. Studies on the pathogenesis. Mucosal lesions were produced in feline small intestine by evoking a simulated intestinal shock (local hypotension at 30 mm Hg and stimulation of regional sympathetic vasoconstrictor nerves at 6 Hz for 2 h). The degree of mucosal damage was correlated to the level of intestinal blood flow. Microscopically characteristic lesions developed regularly in the small intestinal mucosa when intestinal blood flow was reduced below 12 ml/min X 100 g during the regional shock. The mucosal damage was graded histologically. No difference was found between untreated controls and cats in which the intestinal lumen was perfused with nitrogenated saline. Perfusion with oxygenated saline and i.v. injections of methylprednisolone on the other hand, prevented almost completely the development of the lesions. Albumin, activated charcoal and aprotinin instilled into the intestinal lumen reduced to some extent the mucosal damage. The obtained data support the view that hypoxia is the key factor in the pathogenesis of the mucosal lesions. However, epithelial and intraluminal enzymes are probably important contributing factors.


The intestinal mucosal lesions in shock. II. The relationship between the mucosal lesions and the cardiovascular derangement following regional shock. The relationship between the mucosal lesions in the gut, observed after a 2-hour period of regional hypotension, and the blood pressure fall seen after the hypotensive period was investigated in cats. Untreated controls were compared to animals treated with intraluminal perfusion with nitrogenated or oxygenated saline or treated with intraluminal instillation of albumin, activated charcoal or aprotinin or i.v. injections of methylprednisolone. Untreated controls and cats perfused with nitrogenated saline exhibited a pronounced reduction in arterial blood pressure during the first posthypotensive hour. In the animals treated with methylprednisolone or perfused intraluminally with oxygenated saline only a small fall of blood pressure was observed. In the remaining groups of animals a moderate blood pressure reduction was noted. These results suggest a causal relationship between the intestinal mucosal damage and the posthypotensive cardiovascular derangement possibly via the release of cardiotoxic material from the hypoxic intestinal villi.


Mitogen-induced membrane changes and cell proliferation in T lymphocyte subpopulations. Rabbit thymus-dependent lymphocytes were exposed to phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) or anti-immunoglobulin at various stages of maturation. Proliferation (induction of DNA synthesis) and early membrane events (turnover of membrane phospholipids) were measured in neonatal thymocytes, normal adult thymocytes, prednisolone-resistant thymocytes and lymph node lymphocytes. In immature thymocytes PHA induced only a marginal increase in DNA synthesis. The mitotic response increased with maturation, but only peripheral T lymphocytes exhibited maximum stimulation. Con A and PWM were able to induce DNA synthesis in immature thymocytes and the degree of stimulation was shown to increase with maturation. In contrast to the different degree of proliferation of thymocytes induced by PHA or Con A the incorporation of [14C]oleate, [14C]choline or [14C]acetate into phospholipids was stimulated to the same degree by these lectins. Reactivity of T lymphocytes, as measured by early membrane changes at different stages of maturation, to different T cell mitogens appears to be identical. Differences in degree of cell proliferation therefore may be secondary phenomena due, in part, to tissue culture conditions. Reactivity to mitogens as measured by phospholipid turnover appears to be an early acquired function in the maturation of lymphocytes of the T cell line.


B cell tolerance induced by polymeric antigens. IV. Antigen-mediated inhibition of antibody-forming cells. The role of antibody-forming cell (AFC) blockade in the genesis of hapten-specific tolerance induced by hapten (2,4-dinitrophenyl)-coupled pneumococcal polysaccharide (DNP-lys-S3) was investigated. Tolerizing doses of DNP-lys-S3 given to mice making antibodies to DNP-hemocyanin a day before assay markedly reduced numbers of detectable anti-DNP AFC. Furthermore, anti-DNP AFC were specifically inhibited by brief in vitro incubation with DNP-lys-S3, followed by extensive washing. This inhibition requires multivalent binding of tolerogen to immunoglobulin receptors on AFC, and appears to result from a decrease in the rate of antibody secretion per cell. A variety of data indicate that IgM AFC are more susceptible to blockade than IgG AFC, and the susceptibility of both cell types decreases with time after immunization. This probably reflects differences in the density and in the rate of loss of surface immunoglobulin receptors on IgM and IgG AFC and their immediate precursors. However, we conclude that under "conventional" tolerizing conditions, i.e. when tolerogen is given prior to immunogen, DNP-lys-S3 suppresses antibody formation primarily by inactivating DNP-specific precursor cells. AFC blockade is therefore probably only relevant in the suppression of (primary?) IgM responses by large doses of tolerogen. The relative importance of precursor inactivation and AFC blockade in tolerogenesis of IgM responses to T cell-independent antigens (such as S3) remains to be elucidated.


Lymphocyte stimulation by protein A of Staphylococcus aureus. Protein A from Staphylococcus aureus (SpA) is known to bind to the Fc region of most mammalian IgG classes. In the present article data are presented showing that SpA is a highly efficient mitogen for human peripheral B lymphocytes, with no detectable activity for T lymphocytes. In order to achieve optimal stimulating conditions SpA should be presented to the lymphocytes on an insoluble matrix, such as the SpA-positive bacteria themselves or SpA covalently attached to Sephadex or Sepharose beads. Using such conditions SpA is equivalent with regard to stimulatory capacity for B lymphocytes as phytohemagglutinin is for the human T lymphocytes. Specificity controls proved beyond doubt that SpA and not any other contaminating product is the B cell mitogen. It is concluded that SpA as an inducer of human B lymphocyte division might serve as a highly useful assay in the clinical assessment of B lymphocyte function. It should also be a suitable tool in the fine analysis of B lymphocyte activation via the specific interactions with surface IgG molecules.


Studies on the activation of mouse bone marrow-derived macrophages by the macrophage cytotoxicity factor (MCF). The capacity of bone marrow-derived macrophages to be rendered cytotoxic by macrophage cytotoxicity factor (MCF) at different stages of maturation was tested. Under in vitro conditions not only mature macrophages but also nonadherent precursor cells were successfully activated. Mature adherent bone marrow macrophages can be rendered cytotoxic for up to three weeks in tissue culture. Cytotoxic effects are demonstrable even at a killer target ratio of 0.5:1. Granulocytes do not respond to activation with MCF. Bone marrow-derived macrophages can be collected at early stages of maturation, when they grow in suspension or have developed only loose adherence. Macrophages which have differentiated in vitro from bone marrow never show any signs of nonspecific activation as measured by our cytotoxic assay system.


Identification of a high molecular weight protein on the surface of murine thymus and thymus-dependent cells. Rabbit anti-mouse Ig reacted with mouse thymocytes resulting in the formation of caps which were shed into the medium and subsequently injected into rabbits. The antiserum from these animals (AMTP) reacted strongly with thymocytes and peripheral T cells and weakly with B cells. The antiserum did not react via the Thy-1 antigen and could be made specific for T lymphocytes by absorption with B lymphocytes. By surface labeling of lymphocytes with 125I, it could be shown that the major T lymphocyte antigen recognized by AMTP was one, or possibly two, large, single chain molecules with a molecular weight of approximately 200000. This molecule was not Ig and, furthermore, the AMTP did not react with cell surface Ig of B lymphocytes. The implications of this finding for previous reports on the existence of immunoglobulin on T lymphocytes are discussed.


Suppressor cell induction in vitro. II. Cellular requirements of suppressor cell induction. The cellular requirements for the induction of antigen-specific suppressor cells (SC) in vitro were studied. Macrophage depletion, by either nylon wool or polystyrene columns or iron (and magnet) treatment or a combination of methods, did not diminish SC induction, in contrast to its effect on helper cell induction. The requirement for T-T interaction in SC induction using splenic T cells was studied by the use of adult thymectomy and anti-lymphocyte serum, which selectively deplete short-lived and recirculating T cells respectively. Since suppressor cell induction was markedly diminished, or abolished by either procedure, but reconstituted by mixing these 2 populations, it was concluded that there was T-T interaction in the development of SC, just as there is in the induction of other T cell reactions, such as the graft-versus-host response, the T killer cell response, the helper cell response and, tentatively, delayed hypersensitivity. By the use of double-chamber tissue culture flasks, with the 2 cell populations separated by a cell impermeable membrane, it was found that T-T interaction does not require cell contact and is thus mediated by factor(s). The direct precursor of antigen-specific suppressor cells is resistant to adult thymectomy but sensitive to anti-lymphocyte serum.


Effects of levamisole on spontaneous rosette-forming cells in murine spleen. Levamisole, an anti-anergic chemotherapeutic agent, is shown to depress the azathioprine sensitivity of rosette-forming cells (RFC) in the spleen of normal mice, and to restore the azathioprine sensitivity of RFC in the spleen of adult thymectomized mice. Using the fully active dose of 1.25 mg/kg i.v., the restoration effect was present 15 h after treatment with the drug and almost disappeared after 48 h. Levamisole was ineffective on RFC in vitro. These results suggest that Levamisole might interfere with the reactivity of T lymphocytes as has been described for drugs interfering with cyclic nucleotide metabolism.


Lymphocyte-mediated cytotoxicity against tumor cells II. Characteristics and tissue distribution of concanavalin A-activated cytotoxic effector cells. In vivo or in vitro activation of cytotoxic effector lymphocytes by concanavalin A (Con A) has been shown to result in a population of effector cells exhibiting a degree of immunological specificity when Con A was present during the cytotoxic assay (Waterfield, J.D. et al., Cell. Immunol. 1975. 17:392). In this communication we have characterized the Con A-activated effector cell by physical criteria and tried to assign it to a given subpopulation of thymus-derived lymphocytes. It was shown that macrophages played no role in target cell lysis in this system, nor was their presence required for Con A activation of the effector cell. The effector cell proved insensitive to anti-theta serum, but was classified as a T cell by the enrichment of cytotoxicity when a purified population of T cells was activated by Con A in vitro and by the failure to activate the effector cell in nude mice. Precursors of the effector cell were shown to reside primarily in the spleen, to be radioresistant up to 400 R, and to be short-lived after adult thymectomy. Thus, the effector cell can be classified with the T1 population of T cells and has similar characteristics as a cytolytically active cell described by Stobo et al. (J. Immunol. 1973. 110: 362, 652).


Activation of T lymphocytes to M locus determinants in vivo. I. Quantitation of T cell proliferation and migration into thoracic duct lymph. Proliferative responses to M locus (Mls) determinants were investigated in vivo by injecting T cell-containing populations intravenously into irradiated H2-identical, Mls-incompatible mice. Responses were studied 1-6 days later by measuring levels of radioactivity in the spleen and lymph nodes of the recipient 45 min after intravenous injection of tritiated thymidine. High responses were observed against Mlsa and Mlsd determinants, i.e. determinants which give strong proliferative responses in vitro. With injection of thoracic duct lymphocytes (TDL), lymph node or thymus cells, the responses, both in the spleen and the lymph nodes, reached a peak at day 3-4 and then fell sharply. This was in marked contrast to the stimulation observed with H-2-incompatible mice where, with TDL or lymph node cells (though not with thymus cells), responses were low at day 3-4 but reached high levels at day 6. Significant responses were also observed against Mlsb and Mlsc determinants, i.e. determinants which stimulate poorly in vitro. The kinetics of this response differed from that against Mlsa or Mlsd determinants in in that proliferation was very low at day 4 but high at day 6. No evidence was found that the responses observed reflected "back-stimulation" by the host. Since congenic resistant strains were not used, the possibility that the stimulation observed was in fact due to minor transplantation antigens rather than Mls determinants could not be excluded. Large numbers of blast cells appeared in thoracic duct lymph of mice sustaining responses to Mlsa or Mlsd determinants. Nearly all of these cells had recently synthesized DNA and entered the lymph after day 3.


Role of macrophages in the generation of T helper cells. IV. Nature of genetically related factor derived from macrophages incubated with soluble antigens. Macrophages incubated with soluble antigens for 1-4 days release factors capable of inducing T helper cells. The nature and some of the properties of this genetically related macrophage factor (GRF) were investigated. By use of immunoadsorbents, GRF was shown to contain I region-coded products (Ia antigens) linked to a small antigenic fragment. The genes coding for the Ia antigens detectable in GRF lie in the I region of the H-2 complex. GRF does not react with anti-immunoglobulin, anti-C3 or anti-human beta2-microglobulin antisera, and its activity cannot be removed by antigen immunoadsorbents. GRF is heat-labile, sensitive to proteolytic enzymes and has a molecular weight of about 55 000 Daltons. The relationship of GRF to other factors known to contain I region-coded products and reported to be effective in cell cooperation is discussed.


B cell tolerance induced by polymeric antigens. V. Different avidities of primed and virgin precursor cells for paucivalent antigen. We have compared the avidity of virgin and primed hapten-specific precursor cells for DNP-lys-S3 (dinitrophenylated type 3 pneumococcal polysaccharide) by measuring its capacity to prevent them from binding highly radioactive DNP-hemocyanin, and thereby protect them from committing hapten-specific "suicide". Moderately substituted conjugates (e.g. DNP-lys2.7S3) protected virgin and memory B cells impartially. In contrast, DNP-lys0.6S3 protected memory cells efficiently, but protected virgin cells only at considerably higher concentrations. These results are consistent with previous evidence - from this and other systems - that there is a higher density of receptors on primed than on unprimed B cells - the significance of which is discussed.


Lymphocyte proliferation in vitro induced by soluble protein antigens. II. Cellular requirements. Immune guinea pig lymph node cells were fractionated on Ig anti-Ig or HSA anti-HSA affinity columns or on plastic surface in medium containing carbonyl iron. These techniques selectively removed B lymphocytes, K lymphocytes or adherent cells. The residual cells (Fc receptor-negative T lymphocytes) responded to soluble antigen in vitro in the same way or even better compared with nonfractionated cells. In addition, there was no indication that antigen-antibody complexes were superior to antigen in triggering lymph node cells or purified lymph code T lymphocytes into DNA synthesis. The results obtained suggested that memory T lymphocytes can be stimulated by antigen autonomously.


The immunological properties of haptens coupled to thymus-independent carrier molecules. IV. The IgG response to dinitrophenylated Ficoll. Dinitrophenylated polysucrose (DNP-Ficoll) elicits T cell-independent IgM anti-DNP antibody formation in mice. This antigen also elicits a heterogeneous IgG1 and IgG2 anti-DNP response, which is operationally as T-independent as the IgM response. However, a concomitant graft-versus-host reaction markedly enhances the IgG response (allogeneic effect). These results confirm those of others, indicating that a certain proportion of the precursors of IgG-producing cells can be triggered by some T-independent antigens. However, our results suggest that even with such antigens optimal triggering of IgG precursors requires T cell help.


Migratory patterns of B lymphocytes. V. Surface Ig and migration properties of density gradient-separated bursa cells. A study was made of bovine serum albumin density gradient-separated bursa cells with respect to their distribution on the gradients, % cytoxicity with anti-Ig + complement (C) or anti-mu + C, and localization of fractions in irradiated syngeneic recipients. Layer A showed a higher cytotoxicity with anti-Ig + C or anti-mu + C than the others; layer D showed the lowest % cytotoxicity, although a large % of the cells not killed by anti-Ig were killed by anti-bursa serum + C. The C + D layers contained a much larger fraction of the Ig+ cells from the bursa in the 1--4-week-old than in the 6--12-week-old animals, suggesting a relative shift towards lower density of Ig+ bursa cells with age. When [3H]adenosine-labeled bursa cells from density gradient fractions were transferred, the % injected radioactivity found in recipient spleens was higher for fractions A and B than for fraction C + D. While 50--60 % of the cells from fractions A and B which localized in spleen were found in germinal centers and follicles, a much lower % of the cells from fraction C + D seen in spleen localized in these areas. The results were in agreement with those of previous studies suggesting that it is primarily the Ig-bearing population among bursa cells which localizes in follicles.


Demonstration that IgG memory is carried by IgG-bearing cells. Memory B cells which give rise to IgG antibody-producing cells were generally assumed to be IgG-bearing cells. However, recent studies indicating that very few IgG-bearing cells exist in lymphoid tissue brought this assumption into question. In this study, we examined directly the question whether IgG-bearing cells contain functional precursors of IgG antibody-producing cells. Using the adoptive secondary immune response, we demonstrated that Ig-1 b-bearing cells, isolated with the fluorescence-activated cell sorter (FACS), are the functional precursors of Ig- 1 b-producing cells. Further, we have enriched IgG2 and IgG1 memory B cells using the FACS. The results show that IgG2-bearing cells are the functional precursors of the IgG2 antibody-producing cells. Likewise, the IgG1-bearing cells are the functional precursors of IgG1 antibody-producing cells. Thus, IgG memory cells have surface IgG which indicates the class and allotype commitment of the memory cell and its progeny antibody-forming cells.


Lack of neonatal susceptibility to induction of tolerance by polysaccharide antigens. Susceptibility to tolerance induction by polysaccharides during the neonatal period has been studied with the alpha-1.3 and alpha-1.6 glucosyl epitopes of dextran B1355 in BALB/c mice and the beta-2.6 fructosyl epitope of levan in CBA mice. Acquisition of responsiveness, as measured by plaque-forming cell (PFC) assays, is relatively late - taking more than 14 days to appear and 2 - 3 months to attain maturity in the case of alpha-1.6 glucosyl and beta-2.6 fructosy. The mice responded well to sheep red blood cells and 2,4-dinitrophenylated (DNP) keyhole limpet hemocyanin (KLH) by 14 days, but were refractory to another thymus-independent antigen DNP-Ficoll. Nonresponsiveness of 2-week-old spleen cells to the polysaccharides was stable on transfer and could not be attributed to suppressor cells. Despite this long post-natal phase of immaturity, no evidence was obtained of concomitant susceptibility to tolerance induction by textran and levan. Response curves in mice injected at birth with weight-adjusted doses revealed similar or even higher "high-zone" thresholds to those tolerized at 3 months. Only partial alpha-1.3 glucosyl tolerance is inducible in adults but this was no greater after neonatal exposure, which led also to short-lived alpha-1.6 tolerance. Repeated injections of B1355 and levan during the first 10 days was no more tolerogenic and PFC appeared spontaneously with maturity in mice given these antigens neonatally. Thus, the recognized neonatal susceptibility to thymus-dependent antigens does not extend to these thymus-independent antigens. It is therefore considered that tolerance studied with polysaccharides has little relevance to the mechanism of self-tolerance acquired in the embryo and, in vivo, is determined by interaction with a relatively mature B cell rather than by "clonal abortion" of a tolerance-sensitive precursor stage.


Human T cell receptor for IgM: specificity for the pentameric Fc fragment. The specificity of the IgM receptor expressed by human T cells cultured in IgM-free media has been investigated. IgM receptors have been detected using a rosette system with ox erythrocytes coated with rabbit antibody (EA(IgM)), and the inhibitory capacity of different IgM fragments in the rosette system has been tested. It was found that F(c)5mu but not F(ab')2mu, nor monomeric IgM (8 S IgM) inhibited EA (IgM) rosette-forming cells. This indicates that the receptor present on the surface of T cells has affinity for a structure located in the Fc portion of the pentameric IgM.


Immunosuppressive activity of Phaseolus coccineus and Phaseolus vulgaris extracts in mice. Lectin mixtures from 10 samples of Phaseolus coccineus and Phaseolus vulgaris beans were used as immunosuppressive agents in the sheep red blood cell (SRBC) antibody response of the mouse. Some bean samples contain lectins capable of inducing several times better suppression of humoral immunity than concanavalin A and phytohemagglutinin tested before in the same immune system. High dilutions of the 10 bean extracts were shown to agglutinate mouse, rabbit and sheep erythrocytes in vitro but the titers and "specificities" did not correlate with the immunosuppressive potency and selectivity displayed by the same extracts in mice. Two immunosuppressive bean extracts, assayed in lymphocyte cultures, were found to stimulate DNA synthesis of murine spleen T cells. This interaction appears to be a necessary step for the reduction of antibody synthesis to SRBC in the whole animal.


Inhibition by mouse serum of hemopoietic colony formation in vitro. The inhibitory activity of BALB/c serum for granulocytic and macrophage colony formation by mouse marrow cells in vitro was separable by flotation centrifugation into the very light density (VLD) fraction. On gel filtration the inhibitory material had an apparent molecular weight of 250,000 and on electrophoresis was localized as a single peak near the albumin region. These inhibitory preparations exhibited lack of specificity and inhibited colony formation by normal B-lymphocytes, lymphoid leukemic, plasma cytoma and mastocytoma cells. Preincubation of C57BL marrow cells at 37 degrees C with high concentrations of VLD fractions was cytotoxic and completely suppressed colony formation. Incubation at 0 degrees C or at 37 degrees C with low VLD concentrations caused a pattern of colony formation similar to that observed in cultures of marrow cells from mice with high serum inhibitory activity (CBA, BALC/c). The lack of specificity of serum inhibitors casts doubt on the role of these inhibitors as specific in vivo regulators of granulopoiesis and monocyte-macrophage formation.