Transient visual impairment following cardiac arrest. This report presents an unusual case of visual impairment following cardiac arrest during general anesthesia. The presumptive etiology was macular capillary insufficiency secondary to vascular stagnation which occurred during cardiac standstill. Ophthalmic examination confirmed areas of macular edema corresponding to localized perifoveal regional infarcts. Isolated macular infarction is not a unique condition and has been reported in hemoglobulinopathies, diabetes, and other systemic diseases.


Anti-DNA antibody in serum measured by radioimmunoassay (Farr technique). Description of method and recommended procedure. Anti-DNA antibody determination in serum is increasingly used because it supports the diagnosis of systemic lupus erythematosus (SLE) with high selectivity. The present work evaluates several of the technical variables of the Farr radioimmunoassay for anti-DNA antibody determination and describes a recommendable procedure, emphasizes the most important sources of error and gives the range of normal blood donors and a group of hospital patients without SLE.


Identification of activated T cells in sarcoidosis. When peripheral blood lymphocytes are stimulated by mitogens or allogeneic cells, they acquire the capacity to form stable rosettes at 37 degrees C with sheep red blood cells, thereby identifying a population of activated T cells. In 7 consecutive patients with acute sarcoidosis, there was a significant (P less than 0.005) increase in the proportion and the total number of peripheral blood lymphocytes forming stable rosettes at 37 degrees C compared to age-matched normal control subjects (mean +/- SE, 12.6 +/- 3.0 versus 2.0 +/- 0.3 per cent, respectively). This occurred despite a significant decrease in the total number of lymphocytes (P less than 0.01) and T cells (P less than 0.001) in the peripheral blood in these same patients. Light and electron microscopic examination of sarcoid lymphocytes confirmed that cells forming stable rosettes at 37 degrees C were activated or atypical. Thus, in acute sarcoidosis, activated T cells are increased, whereas the total number of T cells is decreased in peripheral blood. This finding also posed certain technical problems in identifying B cells by surface immunoglobulin and complement receptors. Measures to overcome these difficulties are discussed. As determined by 2 independent tests of B cells (i.e., complement receptor and surface immunoglobulin), the number of circulating B cells was decreased.


Isoniazid induction of antinuclear antibodies. A prospective study. We prospectively studied 102 patients admitted to the Chest Service with tuberculosis. Four patients (4%) had antinuclear antibodies before therapy and 22 patients (21.6%) developed antinuclear antibodies after treatment. None developed lupus erythematosus cells or signs or symptoms of systemic lupus erythematosus. Age and race were not related to the induction of antinuclear antibodies. The percent of positive sera was similar during and after 3 months of treatment, with higher titers after 3 months of therapy. Although patients were treated with various antituberculosis drugs, isoniazid alone or in combination with other drugs induced antinuclear antibodies.


[The action of levamisole on thymodependent rosettes in normal and atopic subjects]. Thymo-derived E-rosettes and fast E-rosettes have been determined in 26 normal and 17 atopic patients. The effect of levamisole in vitro has been studied by adjunction in the cell suspension at a concentration of 100 gamma/ml. In normal and atopic subjects the E-rosettes are not modified by levamisole. Fast E-rosettes are significantly increased by levamisole in normal but not in atopic patients. These results support the hypothesis of a functional deficiency of T-lymphocytes in atopy; they are correlated by the failure of treatment of atopic dermatitis by levamisole.


Modulation versus rescue of antimetabolite toxicity by salvage metabolites administered by continuous infusion. A system has been developed for the long-term continuous intravenous infusion of chemotherapeutic agents into unrestrained mice which allows new approaches to the toxicological and chemotherapeutic evaluation of antimetabolites. In mice, the concurrent infusion of thymidine and a source of preformed purine reversed both the toxicity and antitumor activity of MTX comparable to what was previously observed in cell culture. The infusion of thymidine alone, however, also blocked the toxicity of MTX without interfering with antitumor activity. A comparison of leucovorin rescue versus the utilization of thymidine plus preformed purine indicated that these salvage metabolites were as effective as leucovorin in reducing the toxicity of high-dose MTX while retaining antitumor activity.


Acidometric agar plate method for ampicillin susceptibility testing of Haemophilus influenzae. The need for an accurate and rapid method of testing ampicillin susceptibility of Haemophilus influenzae, especially strains isolated from patients with meningitis and septicemia, is indisputable. Various methods have been employed for this purpose. Each has advantages and disadvantages. This report describes a modification of the capillary acidometric procedure in which an agar plate is substituted for a tube. All beta-lactamase results obtained by this modified technique correlated with minimal inhibitory concentrations determined in liquid media and the chromogenic cephalosporin substrate method. This modified acidometric agar procedure is a simple, inexpensive, accurate, and rapid way to determine H. influenzae susceptibility to ampicillin.


Comparative activities of selected beta-lactam antibiotics against Haemophilus influenzae. The comparative activities of ampicillin, cefamandole, cefoxitin, cefaclor, and cefatrizine against both beta-lactamase-producing and non-beta-lactamase-producing isolates of Haemophilus influenzae were determined by using an agar dilution susceptibility test procedure. Ampicillin was the most active drug tested against non-beta-lactamase-producing isolates, whereas cefamandole was most active against beta-lactamase-producing strains.


Defective neutrophil chemotaxis and raised serum ige levels in a child with recurrent bacterial infections and eczema. Influence of levamisole. A 5 1/2-year-old girl, with a life-long history of recurrent staphylococcal infections and eczematous dermatitis had a defect in polymorphonuclear leucocyte chemotaxis and phagocytosis in autologous serum, a high serum IgE level, and a disturbed T cell function. Levamisole improved all the immunological abnormalities and there was a dramatic clinical improvement. Discontinuation of therapy with levamisole resulted in gradual deterioration.


Effect of storage and heat on antimicrobial proteins in human milk. Human milk, after storage and pasteurisation at 73 degrees C for 30 minutes at a milk bank, was found to have little surviving IgA, IgG, lactoferrin, lysozyme, and C3 complement. Accurate pasteurisation at 62.5 degrees C produced a loss of 23.7% of the lysozyme, 56.8% of the lactoferrin 34% of the IgG, but no loss of IgA. Storage by deep freezing at -20 degrees C for 3 months produced no appreciabile loss of lactoferrin, lysozyme, IgG, IgA, or C3.


Haemophilus influenzae type b pneumonia. Thirteen patients with Haemophilus influenzae type b pneumonia are reported to emphasise the clinical, radiographic, and therapeutic aspects of this illness. All but one patient was under 2 1/2 years of age. The presenting complaint was a variable duration of upper respiratory infection and fever in most cases. One-third of patients had radiographic evidence of pleural involvement; one-third showed a patchy bronchopneumonia on roentgenogram; and the remainder had segmental or lobar infiltrates. Clinical response to antibiotic therapy was prompt in patients without pleural involvement.


Oesophageal variceal bleeding in Felty's syndrome associated with nodular regenerative hyperplasia. Four patients with Felty's syndrome developed massive upper gastrointestinal bleeding due to oesophageal varices. The underlying hepatic pathology in all 4 was nodular regenerative hyperplasia. This appears to be a difficult histological diagnosis to make, having been initially reported as normal on percutaneous biopsy or as fibrosis or cirrhosis on wedge biopsy. This series brings the total number of cases reported in the English literature of this association to 12, suggesting a definite symptom complex. The portal hypertension seems to be due to a combination of increased splenic blood flow and postsinusoidal resistance. The clinical importance of this syndrome is that the  appropriate therapy for bleeding oesophageal varices appears to be shunt procedure such as a splenorenal shunt with splenectomy, which should be well tolerated.


Vascular reconstructive surgery following myocardial revascularization. Survivors of successful coronary bypass have a life expectancy close to normal. Myocardial infarction has been the major cause for morbidity and mortality in patients requiring surgery. Current data suggests that patients who have undergone CAB are not only acceptable risks for subsequent surgery, but may in fact have a lesser cardiac risk than the routine patient. The selection of the proper sequential surgical procedures is critical for patient survival. We reviewed 74 major vascular reconstructive procedures in 53 patients. Twenty-nine cerebrovascular procedures, 20 femoro-popliteal bypasses, aneurysmectomy nine times, and aortic bypass in 16 patients were the procedures performed. Twenty-two abdominal operations were performed with no significant morbidity or mortality. Two patients died during the postoperative period and three have subsequently died. The 48 survivors continue to do well.


Results of interposition "H" grafts for portal hypertension. During the past nine years, 54 patients underwent interposition graft shunting for variceal bleeding in 48 and intractable ascites in six, either electively (35 instances) or as an emergency (13 instances). Autogenous jugular was used in 41 instances, homologous vena cava in nine and Dacron in five. The interposition graft was placed between superior mesenteric vein and vena cava in 36 instances and the portal vein and vena cava in 19. Using Child's Clinical Classification 44 were Class C and 10 Class B. There were six (11%) operative deaths with one (2.4%) in the elective and five (38%) in the emergency group. Encephalopathy was seen in 4 (10%) of those surviving more than one year. Two Dacron and two homografts thrombosed. Eight of the autografts were patent at autopsy, 18 on angiography and 15 assumed to be patent because patients were asymptomatic. Only one of 12 late deaths was related to grafts failure. Apparently the operation controls ascites and the autogenous jugular vein is the ideal material. Interposition "H" grafting is a simple safe procedure that can be used for portal decompression in patients with bleeding varices.


Further evaluation of the surgical treatment of obstructive disease of the left main coronary artery. A protocol for the operative management of two patient groups with left main coronary artery disease has been evaluated. The period prior to and during induction of anesthesia is managed without using aortic balloon counterpulsation. Of the 86 patients undergoing coronary artery bypass for left main coronary artery disease from 1970 to 1973, there was a surgical mortality of 8.1%. Follow-up of the survivors from 48 to 87 months revealed three coronary and five non-coronary related deaths with survival to seven years of 75.6 +/- 5%. If the operative mortality is excluded, there is an observed survival to seven years of 82.4 +/- 4.8%, almost the same as a "normal" population of similar age and sex. Utilizing the same protocol, 90 similar patients undergoing coronary artery bypass in 1976 had an operative mortality of 4.4%. The deaths were not related to induction of anesthesia. The perioperative infarction rate (2%) and postoperative cardiac enzyme determinations were no greater in a random group having the same operation for less severe forms of coronary artery disease during the same time period. This method of management for patients with significant left main coronary artery disease is judged superior to other more complex techniques.


Factors influencing late survival after coronary bypass surgery. In order to determine which factors most influence late survival after the coronary bypass procedure, a review was made of the initial experience of one surgeon who performed 792 operations between 1968 and 1972. The initial 250 patients were compared with the subsequent 542 patients. The two groups were of similar age and sex and had a similar distribution of coronary disease and impaired left ventricular function. Perioperative mortality fell from an initial 6.8% (17/250) to 4.8% (26/542). The number of grafts per patient was initially 1.5 but later was 1.8. Graft patency beyond five years in 105 patients was 88.6% (148/167), 96.2% of patients had at least one patent graft. Initially, crude five year survival was 78.0% (195/250) but was 87.8% (476/542) in the later group. Patients who had no residual unbypassed lesions after operation had a 91.4% (287/314) survival while those with two residual lesions had a 66.7% (14/21) survival. Those patients with a preoperative end-diastolic pressure of less than 15 mmHg and no localized abnormality of contraction had a five year crude survival of 92.1% (316/343) whereas the patients with poor ventricular function had a survival of 81.8% (108/132). Our conclusion is that the most important factors determining late survival are the quality of surgical result achieved as shown by: perioperative mortality and graft patency; the degree of revascularization established; and the preoperative status of left ventricular function. The number of vessels diseased preoperatively had a minimal influence on late survival. These findings emphasize the primary importance of good surgical results in obtaining superior late survival rates.


Criteria for operability and reduction of surgical mortality in patients with severe left ventricular ischemia and dysfunction. A series of 188 patients who were operated on for left ventricular ischemia and dysfunction is presented. Angina was a prominent symptom in all patients, and a history of congestive heart failure could be elicited in 20%. Mean ejection fraction for the series was 0.35, with 67% having an ejection fraction of 0.35 or less 24%, 0.20 or less. Complete revascularization was accomplished whenever possible; more than 70% of the patients had triple-vessel disease, and single bypass was performed infrequently (5%). Factors thought to be important in achieving a low operative mortality (2.1%) were: precise prebypass monitoring, particularly with the V5 precordial lead; maintaining a low rate-pressure product (less than 12,000) prior to bypass; myocardial preservation with cold hyperkalemic or hyperkalemic-hyperosmolar solution; and careful titration of inotropic and vasodilator drugs. Inotropic drugs and intraaortic balloon pumping were used frequently in this series. The late mortality was 4.3%. Angina was completely relieved or improved in 94% of the patients. Those having a history of congestive heart failure had an increased late mortality rate, four times that of the entire series.


Myocardial revascularization in women.

Myocardial revascularization in women. During the period January, 1970, through June, 1977, 1,541 patients underwent coronary artery bypass grafting; 241 of them were women (15.6%). Operative mortality rates for the entire study were 2.4% in men and 3.7% in women, but they showed a marked decline in women during 1975 to mid-1977, with only 2 deaths in 140 patients (1.4%). Women comprised a larger percentage of patients (16.7%) in these later years. Women were slightly older, received fewer grafts, had better preservation of ventricular function on preoperative studies, and had more severe anginal symptoms than men. Patency rates were significantly lower in women at 1 month, 1 year, and 3 years. Five-year survival was not significantly different between women (88.3%) and men (93.5%). Many of these findings may be explained on the basis of women having smaller coronary arteries than men. These favorable results differ from earlier reports of higher mortality rates in women and indicate that myocardial revascularization should not be withheld from female patients.


The short saphenous vein: an alternative to the long saphenous vein for aortocoronary bypass. The long saphenous vein and internal mammary artery are considered at present to be the best grafts available for coronary artery bypass. Patients who have had bilateral long saphenous vein stripping and who require multiple aortocoronary bypass grafts present a challenge to the cardiac surgeon. The short saphenous vein appears to be a suitable alterative.


Endophthalmitis following staphylococcal sepsis in renal failure patients. Endophthalmitis occurred three months following completion of therapy for documented staphylococcal septicemia in two patients on long-term hemodialysis. The indolent course of the endophthalmitis, and its excellent response to systemic and subconjunctival antibiotics and subconjunctival and topical corticosteroid therapy, suggest the possibility that the acute fulminating clinical course of metastatic bacterial endophthalmitis may be modified in this population of patients. The reason for this modified clinical picture is probably the immune incompetence associated with uremia, which favors both the development of metastatic endophthalmitis as well as altering its clinical presentation. While funduscopic examination is suggested in all dialysis patients with eye complaints, this procedure becomes mandatory following episodes of sepsis.


Noncardiac surgery in patients with coronary artery disease. Risks, precautions, and perioperative management. Patients with coronary artery disease face increased risks when they undergo noncardiac surgery. This is attributable to the cardiovascular stress imposed by the surgical procedure and the effects of anesthetic agents on the cardiovascular system. Several approaches to managing patients with coronary artery disease before, during, and after noncardiac surgery include "prophylactic" myocardial revascularization procedures, digitalization, use of propranolol hydrochloride, and insertion of temporary intravenous pacemakers.


Transfer of specific immunity with RNA.

Transfer of specific immunity with RNA. The term "immune RNA" (iRNA), as presently used, refers not to a characterized species of RNA but to phenol extracts of lymphocytes from immunized animals, which have the capacity to transfer a variety of immune products or activities. These include synthesis of specific antibody, development of specific cellular (delayed) hypersensitivity, and production of immunoglobulin allotypic or idiotypic specificities. Recent evidence that iRNA might be used as a specific therapeutic agent to induce immunity to tumors has stimulated an increased interest in this area of research. The purpose of this article is to review the current status of studies on iRNA.


Association and dissociation of visual functions in a case of bilateral occipital lobe infarction. A severe restriction of the visual field was observed in a patient suffering a bilateral occipital lobe infarction. Soon after the lesion, the visual field had an angle of approx. 4 degrees. Some recovery was observed within the following months. Within the restricted visual field, several visual functions were tested. Increment threshold, for instance, was found to be one log unit higher than would normally be expected. Color vision was completely lost soon after the lesion, but some recovery was later observed. Although binocular interaction was demonstrated by the interocular transfer of after-effects, the patient never experienced steropsis. He also seemed unable to recognize faces. Dsepite the small visual field, optokinetic nystagmus could be elicited. A notable slowing down of visual analyses was observed in experiments on visual reaction time, on the inversion of the Necker cube, and on binocular rivalry. The complete loss of certain functions like steropsis or face recognition in contrast to a quantitative reduction of other functions like visual acuity or color perception can be discussed in the light of two conceptual models of perceptual processing. One model suggests the representation of different visual functions within one neuronal network, each function represented by a different number of neurons or a different algorithm within the network. The second model suggests a spatial segregation of different visual functions in different cortical areas that receive input from one common structure, presumably the striate cortex.


[Prosopagnosia and disturbance of color recognition during recovery from cortical blindness]. Neuropsychologic findings during recovery from cortical blindness are described in four right-handed patients (two female, two male) aged 53 to 70 years. The lesions were due to occlusion of both posterior cerebral arteries (Case 1) and vascular spasm following subarachnoidal hemorrhage (Case 3) or angiography (Cases 2 and 4). Complete blindness lasted for 3 months until death in Case 1, 4 weeks in case 2, and 1 to 2 days in Cases 3 and 4.  Confusional states and visual hallucinations were pronounced in three cases. Anosognosia (Anton's syndrome) was most pronounced in a patient with occlusion of both posterior cerebral arteries and less obvious in the remaining patients. During the recovery phase, symptoms of right hemisphere involvement were prominent with left-sided hemianopsia and diminished optokinetic nystagmus to the left, prosopagnosia in two cases, and dysmorphopsia with altered physiognomic recognition in one case. Transient disturbances of color recognition occurred in three patients. The observations are discussed with reference to clinical and neuropathologic findings of the literature.


Precise diagnosis in severe hematochezia. Angiography has clarified the origin of severe hematochezia in many cases. It has demonstrated the frequency of bleeding from colon diverticula on the right side, delineated new causes in occasional instances, eg, angiodysplasia, and underscored the fact that some patients in whom the clinical diagnosis is colonic bleeding may in fact be bleeding proximal to the colon. Although total colectomy has been widely accepted as the operation of choice, better results may be expected for many patients if the bleeding site is pinpointed and lesser resections done. In the case presented, colonoscopy identified the site of bleeding.


[Age and changes in the splenic lymphoid tissue of germ-free rats during the postnatal period of ontogenesis]. In germfree rats the splenic lymphopoiesis is not demonstrated by the investigation to be suppressed, and lymphoid follicules undergo age changes. Up to 15 days, periarterial zone of T-lymphocytes, responsible for cell immunity, is determined, and by the 30th day, as in control animals, peripheral zone of B-lymphocytes, responsible for hormonal immunity, is distinctly observed. In 4-month-old germfree animals, a large amount of free iron crystals is detected in the spleen, while in the organ of control animals its amount is still small. In 10-month-old germfree rats, with the appearance of reactive centers, the zone of B-lymphocytes widens in lymphoid follicules and iron crystals integrate in the red pulp. Lymphopoiesis in the spleen of the germfree rats seems to be maintained by certain local conditions which are connected with increased haemolytic function of the organ. This produces a discharge of a large amount of the products of erythrocytosis which, like autoantigens, stimulate lymphopoiesis in the spleen even when microflora is absent in the organism, while lymphopoiesis in lymph nodes in germfree animals is sharply inhibited.


[Cytoangioarchitectonics of the parasympathetic ganglion of the frog bladder according to findings from studies during life]. The form of neuronal bodies and their interarrangement with capillaries was studied in prevital parasympathetic ganglia in the bladder of the frog (Rana temporaria). The size of the neurons and the diameter of the capillaries were measured. Most of the neurons were stated to have oval form and they are oriented by their long axis along the capillaries, about 20% neurons have contacts with 2--3 capillaries; some neurons have no contacts and their distance from the nearest capillary is 32--26 mkm. Intermediate structure may be either a connective tissue or neuroglia, or (seldom) other neuronal cells. Unequal conditions of neuronal blood supply, as the author believes, demonstrate their different metabolism and various levels of their functional activity.


[Experience in creating an automated pathoanatomic archive in prosection at the A. N. Bakulev Institute of Cardiovascular Surgery of the Academy of Medical Sciences of the USSR]. An information system "Automatic pathological anatomy archive" has been created in the cardiac surgery center existing 22 years. A special card has been developed for resording of the results of morphological examinations and the main information on the patient, which is filled by the dissector after autopsy. Treatment of the data contained in the information mass stipulates an urgent search of the cases according to the set of data indicated in the request, interpretation of the content of unified cards for the selected cases, calculation of per cent ratios, etc. Realization of information systems in universal computers opens wide possibilities for principally new organization of pathological archives.


Metastatic coccidioidal endophthalmitis. A severe granulomatous iridocyclitis developed in association with a cavitary pulmonary lesion in a 29-year-old man. The initial diagnosis and treatment was for pulmonary tuberculosis with tuberculous uveitis. Although the pulmonary lesion improved with antituberculous therapy, the condition of the eye deteriorated. An anterior-chamber tap was positive for Coccidioides immitis, and the patient was treated with intravenous and two intracameral injections of amphotericin B. The eye was ultimately enucleated three weeks after the initial intracameral injection, and yet was culture-positive for the organism. Histopathologic examination disclosed diffuse involvement of the anterior segment, with multiple spherules present within the iris and limbus.


Visualization of small extracanalicular neurilemomas by metrizamide cisternographic enhancement. Metrizamide (Amipaque) computerized tomography cisternography (CTC) provides a rapid, simple, and accurate radiographic modality of intrathecal enhancement for detecting and morphologically characterizing cerebellopontine (CP) angle masses. The technique is of especial value in masses greater than 1.5 cm that are not detected on intravenously enhanced computerized tomography. Metrizamide CTC was used in six patients with no CP angle mass and in four patients with acoustic neurilemomas.


Isolation and partial characterization of rabbit plasma alpha1-antitrypsin. Alpha1-Antitrypsin was isolated from rabbit plasma by salting out with (NH4)2SO4 followed by ion-exchange chromatography either on DEAE-Sephadex or DEAE-cellulose (each at pH8.8 and 6.5), and affinity chromatography on Sepharose-Cibacron Blue and Sepharose-concanavalin A. The protein thus obtained was homogeneous during crossed immunoelectrophoresis by using an antiserum to whole rabbit plasma, but it migrated as two broad bands when electrophoresed in alkaline polyacrylamide gels. Under optimal loading conditions, two or three subcomponents could be distinguished in each band. The two major forms of rabbit alpha1-antitrypsin, designated components F and S, were separated by preparative polyacrylamide-gel electrophoresis, and some of their physico-chemical properties were established. Both forms reacted with trypsin at a molar ratio of 1:1. Their elution volumes from a Sephadex G-200 column were identical, corresponding to a mol.wt. of 58000; however, some heterogeneity was observed after sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Isoelectric focusing in polyacrylamide gel in a pH 4-6 gradient revealed a multiple-band pattern for each form in the range of pH4.4-4.9. The two forms of rabbit alpha1-antitrypsin possessed the same N-terminal amino acid (glutamic acid) and had very similar amino acid and carbohydrate compositions.


Serologic studies in patients with systemic lupus erythematosus and central nervous system dysfunction. Serologic studies were performed on 25 patients with systemic lupus erythematosus (SLE) during 29 acute episodes of central nervous system (CNS) disease. Increased anti-DNA antibody and decreased total serum hemolytic complement activity were observed only in those patients with associated extra-CNS disease manifestations. Patients with isolated CNS disease were otherwise in apparent clinical and serological remission regarding these two indices. No special association of cold-reactive IgM antilymphocyte antibodies was demonstrable in patients with ongoing CNS injury. Of special interest was an increased incidence of anti-Sm antibodies in the patients with CNS dysfunction relative to that in a large group of patients without neuropsychiatric disease. The incidence of anti-RNP was not increased. The data do not support direct involvement in SLE brain injury of either DNA/anti-DNA complexes or of lymphocytotoxic antibodies cross-reactive with brain cells, but do suggest an association of anti-Sm with CNS disease in this disorder.


Prevalence of rheumatic diseases as causes of disability and complaints by ambulatory patients. Data from the National Health Survey reveal that musculoskeletal diseases are the most prevalent cause of chronic disability among the civilian, noninstitutionalized population. Because of the frequency of musculoskeletal injuries, rheumatic disorders are the second most common cause of acute disability. Problems referable to the musculoskeletal system constitute the second most frequent class of complaints presented by patients to office-based physicians. Only respiratory and circulatory diagnoses are recorded more often by such physicians.


Absence of B stem cells in spleens of chickens fed the androgen analog mibolerone. Bursa-derived stem cells in the spleens of chickens treated with the androgen analog mibolerone or with cyclophosphamide and in the spleens of untreated controls were examined by a transplantation technique. Spleen cells from syngeneic donors 2-20 weeks old were transferred to syngeneic cyclophosphamide-treated recipients, and the immunocompetence of the recipients was tested 5 weeks after the transfer by antigenic stimuli with sheep erythrocytes and Brucella abortus. Spleens of mibolerone-treated chickens failed to reconstitute the immunologic capability of cyclophosphamide-treated recipients in a manner similar to spleen cells from normal donors. Spleens of cyclophosphamide-treated donors did not contain stem cells. Stem cells were detected in the spleens of untreated controls as young as 2 weeks old; activity was highest after the 13th week of age.


Lung function in alpha-1-antitrypsin deficient sisters. Two sisters were found to homozygous for alpha-1-antitrypsin deficiency. One was disabled by breathlessness and had advanced clinical and radiological emphysema which was confirmed on lung function testing. The other, of similar age and smoking history, was symptom-free with a normal chest radiograph. She had a slightly increased airways resistance, a reduced gas transfer, a bilaterally reduced apex--base perfusion gradient and a small but generalized increase in physiological dead space in all zones. The minor pulmonary and vascular abnormalities present in the younger sibling suggest that we are witnessing early changes in the evolution of the panacinar emphysema characteristic of alpha-1-antitrypsin deficiency. The reason for the different rates of progress of the disease in these two sisters is not understood.


[Rosette forming lymphocytes as prognostic indices in idiopathic thrombocytopenic purpura]. The study included 12 patients with acute ITP to whom subpopulations of rosette forming lymphocytes were determined in peripheral blood and in serial form, the number of platelets to establish a correlation as prognostic index in the evolution of the disease. No correlation was found between the progressive increment of platelets in the evolution of the disease. However, in patients with a tendency to remission, the percentage of E(T) rosette forming lymphocytes was low and normal that of EAC (B) lymphocytes. Dissimilarly, it was seen that in patients without tendency to remission, the percentage of T and B rosette forming lymphocytes was within normal limits. This seems to show that determination of the subpopulations of lymphocytes may be useful as a prognostic index in this stage of the disease.


The sympatomatic treatment of carcinoma of the bronchus using combination chemotherapy. A study was made of chemotherapy for inoperable carcinoma of the bronchus. Only patients with symptoms directly due to the tumour or with evidence of rapid tumour growth were selected for treatment. Half the patients selected in this way responded and in these patients survival may have been prolonged. The regimen chosen caused the minimum of interference with the patient's life and, by relief of symptoms, appeared to offer an improvement in the quality of life.


[Concentration and activity of alpha-1-antitrypsin in neonatal hepatitis]. The concentration and activity of alpha 1-antitrypsin were studied in 20 children with the diagnosis of neonatal hepatitis. The concentration of alpha 1-AT was found normal or high in all of the patients (3.6 +/- 0.12 mg/ml). No case was found with PiZZ homozygote type alpha 1-AT deficiency. The activity of alpha l-AT was found decreased in 90% of the patients with neonatal hepatitis (control: 0.86 +/- 0.18 mg. trypsin inhibited by ml. of serum; neonatal hepatitis: 0.49 +/- 0.07 mg/ml.). The possibility that this may correspond to a disorder characteristic of neonatal hepatitis is mentioned.


Structure of the oligosaccharides of three glycopeptides from calf thymocyte plasma membranes. The carbohydrate composition and oligosaccharide structure of three glycopeptides isolated from delipidated calf thymocyte plasma membranes following Pronase digestion have been determined. Five major glycopeptide fractions were separated using Bio-Gel P-6 gel filtration and diethylaminoethylcellulose chromatography. The structure of the oligosaccharide chains of three of these glycopeptides was determined by a combination of sequential degradation with glycosidases and methylation analysis. These oligosaccharide structures consist of complex, highly branched N-linked chains containing at their nonreducing termini the unusual sequence Gal(beta1 leads to 3)Gal(beta1 leads to 4)GlcNAc leads to as well as the more usual sequence SA(alpha2 leads to 3)Gal(beta1 leads to 4)GlcNAc leads to. In addition, one glycopeptide also contains short O-linked chains with the structure Gal(beta leads to 3)GalNAc leads to Ser(Thr) which have receptor activity for the lectin from the mushroom Agaricus bisporus.


[Alpha-1-antitrypsin in the newborn with idiopathic respiratory distress syndrome]. The study included 50 newborns with (RDS) and 41 controls in relation with the plasma concentration of alpha-antitrypsin (a-l-AT) and of proteins. The blood samples were taken at 24, 72 and 120 postnatal hours. At 24 hours, in infants with IRDS 187.5 +/- 9 mg/dl of a-l-AT were shown and 4.15 +/- 0.09 g. % of total proteins, which compared with concentrations of a-l-AT and total proteins in controls of the same age, turned out significantly lower. The a-l-AT and total proteins suffered increment in their concentrations at 72 hours of life in relation to control cases in whom there was no modifications in the course of postnatal age. Among other factors, a drop in total protein was considered related to the drop in globulin fraction. The usefulness of quantification of a-l-AT for the diagnosis of IRDS, is pointed out at the end.


[Influence of temperature on blood coagulation in vitro (author's transl)]. The influence of different temperatures between 13 degrees C and 45 degrees C on coagulation factors in vitro was studied by measuring clotting time with the recalcification time, partial thromboplastin time (PTT), and thromboplastin time test. In all three tests the shortest clotting times were measured at a temperature of 40 degrees C. The relation between temperature and clotting time was similar in fresh plasma and in plasma which had been stored at a temperature of --20 degrees C before examination. However, in all tests stored plasma showed shorter coagulation times. Prolongation of coagulation time at 45 degrees C is caused by irreversible reduction of coagulation activity in the plasma. At the same time thromboplastin- and PTT-reagent are imparied in their coagulation acitvity by a temperature of 45 decrees C. In comparison to plasma obtained from healthy persons plasma from patients with hemophilia A or B or with v. Willebrand's disease reacted more sensitive to changes in temperature in the PTT test. The coagulation defect was definitely more pronounced at 27 degrees and 17 degrees C than at 37 degrees C. It was not possible to differentiate these three coagulopathies with the PTT test at 27 degrees and 17 degrees C.


[Participation of phospholipases in the "repair" of photoreceptor membranes subjected to peroxidation]. Results are presented showing that Ca++-activated endogenous phospholipases are able to catalyze hydrolysis of hydroperoxydiacyglycerophosphatides with subsequent formation of monoacyglycerophosphatides and free hydroperoxides of fatty acids in frog rod outer segment membranes. The role of endogenous phospholipases in the mechanisms of repair of photoreceptor membranes subjected to lipid peroxidation, as well as in "molecular substitution" of phospholipids under membrane renewal is discussed.


The importance of the anomalous left gastric artery in the arteriography of gastric haemorrhage. The importance of the occasional anomalous origin of the left gastric artery (LGA) from the aorta in the arteriographic evaluation of gastrointestinal haemorrhage is illustrated by two cases. The incidence of the anomaly is between 2.5 and 5.4% and should be considered when the LGA is not opacified on a coeliac arteriogram.


Vestibulogenic imbalance.

Vestibulogenic imbalance. Vestibular lesions may cause imbalance that long outlasts vertigo. Photographic analysis in five cases showed defects not only of the tilting reactions, which are of labyrinthine origin, but also of certain other postural reactions, notably the counterpoising and protective stepping reactions. All of these reflexes are unconscious and consequently such patients are rendered unstable in several ways simultaneously and may have difficulty describing their symptoms.


The effect of electric fields on osteoporosis of disuse. An experiment originally done by McElhaney et al. was repeated to obtain additional information about the effects of electrical fields on osteoporosis of disuse. The right femurs of 35 male rats were immobilized in plaster casts. Sixteen rats were treated with transcutaneous electrical fields of 30 Hz and approximately 100 V/cm for periods of 2 or 8 h a day. While the right femurs of the untreated rats were found to be atrophic with respect to the opposite limb, in the treated rats the immobilized femur was made larger than the opposite bone. Longer daily treatments exaggerated this effect. The tumors found in the previous study were not seen in our experiments. Other similarities and differences in the 2 studies are discussed.


[Mortality in the emergency surgical management of upper gastrointestinal hemorrhage due to ulcers and gastritis]. A retrospective study of 68 patients with acute upper gastrointestinal bleeding (excluding bleeding from esophageal varices) revealed that all patients had emergency surgery. The factors influencing the mortality and the recurrent bleeding have been sought. The overall mortality was 29.5%. Age of patients and type of surgical procedure did not affect the mortality raate, while chronicity of lesions and their duodenal location had a favourable influence. Most deaths were due to hypovolemic shock and its complications. Gastric resection with vagotomy is the operation of choice for control of bleeding. The authors present a brief review of the literature and stress the importance of early diagnosis and resuscitative measures, as well as the need for aggressive surgical intervention.


Strength-duration properties of single units driven by electrical stimulation of the lateral hypothalamus in rats. Cathodal strength-duration functions were measured for 27 single units which were driven by electrical stimulation of the lateral hypothalamus. The distribution of chronaxies of these units showed four clusters at about 0.1, 0.25, 0.4 and 0.5 msec. These chronaxies are not fundamentally different from those previously reported for peripheral nerve. Two units fired repetitively during a long-duration stimulation pulse. Anodal strengitation. The data are discussed with reference to behaviorally determith duration properties were obtained from 14 units. Four units were not excited by anodal pulses of any strength or duration, four were excited during an anodal pulse (anode-make excitation) but not at the termination of the pulse (anode-break excitation), and six showed both anode-make and anode-break excitation. The data are discussed with reference to behaviorally determined strength-duration functions for brain stimulation reward.


Bacterial infections in pediatric Hodgkin's disease: relationship to radiotherapy, chemotherapy and splenectomy. The occurrence of bacterial infections (B.I.) among 181 children with Hodgkin's disease (121 with splenectomy, 60 without splenectomy) was analyzed. Twenty-seven B.I. occurred among 22 children and included 15 episodes of bacteremia-meningitis in 14 children. B.I. occurred in all age groups, but bacteremia-meningitis occurred most commonly in splenectomized children 10 years of age or less. The frequency of B.I. in splenectomized children receiving radiotherapy was 1.4%, compared to 18.3% among those receiving chemotherapy (p less than 0.05); the frequency of B.I. among non-splenectomized children receiving radiotherapy was 2.8%, compared to 23.1% among those receiving chemotherapy (p less than 0.05). There was no difference in the probability of B.I. as a function of splenectomy for the corresponding groups, although all cases of Streptococcus pneumoniae and Hemophilus influenzae bacteremia-meningitis in splenectomized children. Overwhelming postsplenectomy bacteremia infection not related to active disease or treatment occurred in 3/121 (2.5%) children, accounting for only one fatality (0.8%).


Profound radiosensitivity in "leukemic" T-cell lines and T-cell-type acute lymphoblastic leukemia demonstrated by sodium [51Cr]chromate labeling. Radiation sensitivity was determined by measuring spontaneous release from 51Cr-labeled cells in various lymphoid cell populations. Among six leukemia T-cell lines originating from acute lymphoblastic leukemia, four such lines were found to be highly radiosensitive. In contrast, two of the leukemic T-cell lines and four normal control B-cell lines were not radiosensitive. Thymocytes from six patients and leukemia T-cell blasts from three patients with T-cell leukemia were likewise found to be highly radiosensitive, whereas leukemic blasts from six patients with null-cell (non-T, non-B-cell) acute lymphoblastic leukemia were not radiosensitive. Normal peripheral blood lymphocytes and mitogen-induced normal lymphoblasts were found not to be radiosensitive. The results indicate that measurement of the radiation sensitivity of acute leukemic blasts may have a therapeutic significance in coping with the heterogeneous nature of individual leukemia cases.


An improved assay method for amylase activity using an amylodextrin fraction as substrate. A rapid and simple method for determination of amylase activity, by using a fraction of amylo-oligosaccharide (amylodextrin, 1) as substrate, is described. The sample solution is incubated with a solution of 1 and the substrate consumed is estimated by measuring the difference in absorbance at 460 nm. The Km value of 1 is about half that of starch. The homogeneity of 1 in its chemical structure and molecular weight facilitated the specification of amylase units according to the international definition. This procedure was applied for assay of human-serum amylase with excellent reproducibility. This method did not require a large dilution factor, as the standard curve showed a linear relationship over a wide range of amylase concentrations.


Repetitive attack by Aspergillus oryzae alpha amylase. The action of Aspergillus oryzae alpha amylase on reducing-end, and uniformly radiolabeled maltotriose through maltodecaose has been studied. The enzyme is found to hydrolyze more than a single glycosidic bond during enzyme-substrate encounters. The extent of this repetitive attack is quantitated.


A purification of Helix pomatia alpha amylase involving a novel affinity-binding procedure. Shellfish glycogen was cross-linked by treatement with cyanogen bromide followed by 1,6-diaminohexane. The resulting, insoluble product efficiently adsorbed Helix pomatia alpha amylase [(1 linked to 4)-alpha-D-glucan glucanohydrolase] from crude solutions of the enzyme at 0 degrees, but only poorly at higher temperatures. A method was developed for the purification of Helix pomatia alpha amylase involving formation of an enzyme-adsorbent complex in the cold and recovery of the alpha amylase by suspending the washed complex in buffer at 37 degrees. After chromatography of the desorbed alpha amylase on a column of Bio-Gel P-60, the enzyme was homogenous as judged by poly(acrylamide)-gel electrophoresis. An overall purification of 360-fold was achieved with a recovery of 35%.


On T-tubule openings at the sarcolemma of white fast-twitch muscle fibres in fish and frog. In "white" muscle fibres of a teleost fish T-tubule openings may occur regularly at all Z-disc levels between adjacent peripheral myofibrils, the T-tubule openings thus occurring at a density of ca. 0.9 micrometer-2. In frog "white" fibres, T-tubule openings are infrequently seen in material fixed like the fish material. In material prepared according to the albumin method of Gray (1975, 1976 a, b) which renders the muscle fibres swollen, straight tubules or sometimes chains of vesicles instead are seen opening at the sarcolemmal surface. Such tubules occur at a higher density than expected from experiments with local activation of contraction. Lability and dynamics within the T-system normally and during fixation are discussed.


A 'profile' of immune responsiveness in multiple sclerosis. An 'immunological profile' of various indices of B-cell function and T-cell function was developed for the 'early' case of multiple sclerosis (MS). This was compared against two groups of controls comprising age and sex-matched healthy subjects, and patients with other disabling neurological diseases (CNS controls) who were matched for age, sex, and type and duration of disability. Some indices of humoral immune responsiveness, such as the induced primary response to monomeric flagellin and the 'resting' levels of antibody to measles and rubella viruses, showed significant augmentation. Cellular immune deficits were attributed to an illness effect per se because (a) cell-mediated immunity was depressed, but only when compared with that of healthy subjects and not when compared with that of the CNS controls, and (b) transformation responses of lymphocytes to viral antigens were inversely related to disability status. The abnormalities in humoral immune responses demonstrable in this study do not provide an explanation for this disease; if there is a relevant 'immunological fault', the nature of this needs to be sought from within the neuraxis rather than from the systemic circulation.


Selective blocking of T cell-mediated in vitro cytotoxicity to a xenogeneic tumour by anti-immunoglobulin sera. Rejection of a xenograft by BALB/c mice results in a highly potent immune peritoneal population. When these immune cells are analysed by using two in vitro assays in parallel, at least two active cytotoxic mechanisms can be demonstrated. Target cells can be labelled with [125I]iododeoxyuridine (IUdR) before the effector cells are added and the detachment of the DNA from plastic can be used to detect cell-mediated immunity. This is referred to as the direct cytotoxicity test. This assay is largely dependent on T-cell function and evidence is presented here that it can be inhibited by anti-immunoglobulin (anti-Ig) antisera. The second test, which reflects the inhibition of incorporation of IUdR by previously mixed effector and target cells, is called the cytostatic assay. This test, although presumably affected by cytotoxic T cells, also reflects a T-independent mechanism which is not inhibited by anti-Ig sera.


Normal B-lymphocyte function in patients with Lesch-Nyhan syndrome and HGPRT deficiency. Immunological and biochemical studies were carried out in two patients with the Lesch-Nyhan syndrome. No abnormalities of T- or B-lymphocyte function could be demonstrated in the presence of hypoxanthine-guanine phosphoribosyl transferase (HGPRT) deficiency.


A naturally occurring antibody in New Zealand mice cytotoxic to dissociated cerebellar cells. A spontaneously occurring antibody cytotoxic to dissociated cells of the neonate mouse cerebellum was found in the sera of some New Zealand (NZ) mice. No significant activity was found in the sera of six non-autoimmune mouse strains. The degree of cytotoxicity was similar towards both allogeneic and syngeneic cells. Absorption of the cytotoxic sera with brain and kidney homogenates removed the reactivity, while liver removed less reactivity. Absorptions with thymocytes and several other tissue homogenates and cells had no effect on the cytotoxicity levels, nor was there a correlation between the levels of thymocytotoxicity and cerebellar cell cytotoxicity. The antibody cytotoxic for cerebellar cells could not be demonstrated in the cerebrospinal fluid (CSF) of any mice examined, including a mouse with high serum cytotoxic levels. Gel filtration of reactive sera indicated that the antibody is of the IgM class.


Levamisole maintains cyclophsophamide-induced remission in murine lupus erythematosus. Antibodies to DNA in 14 month old male NZB/W F1 mice were markedly decreased after 4 weeks of cyclophosphamide therapy. A group of these mice and untreated controls subsequently received levamisole for 12 weeks. Antibodies to DNA returned to pretreatment levels within 8 weeks in animals receiving only cyclophosphamide, whereas levamisole treatment after cyclophosphamide delayed the reappearance of these antibodies. Glomerular immunoglobulin deposition and the degree of lymphocytic tissue infiltrate were decreased in animals receiving cyclophosphamide followed by levamisole as compared with non-treated control animals or those receiving cyclophosphamide or levamisole alone. In vitro T-cell mitogen reactivity was inversely correlated with the final DNA antibody titres of individual mice, suggesting a relationship between decreased autoantibody production and augmented cellular immunity. We discuss possible mechanisms by which levamisole may delay the reappearance of autoantibodies and decrease the histological evidence of lupus nephritis when given to New Zealand mice first treated with cyclophosphamide.


Angiographic evaluation of gastrointestinal haemorrhage complicating pancreatic disease. Seven patients with gastro-oesophageal varices due to splenic or portal vein obstruction from a diseased pancreas have been seen at the Mater Hospital during the past three years. Four of these patients had episodes of acute and massive gastrointestinal bleeding and this paper emphasises the role of angiography in the management of this complication. In three instances the bleeding was the result of the varices, but in one patient with carcinoma of the head of the pancreas the bleeding was shown to result from invasion of the tumour into the duodenum.


[Most severe liver rupture with hepatic vein avulsion and massive hemobilia]. A case report of hepatic trauma in a patient with polytrauma. For treatment of a destroying lesion of the right lobe with disruption of the middle hepatic vein right lobectomy was done. Postoperatively an excessive hyperbilirubinaemia occurred because of a closed central contusion of the left lobe with a biliovenous fistula. This diagnosis was achieved by arteriography before a second operation and intraoperative cholangiography using a T tube. Bilhaemia completely disappeared while mild negative pressure was administered to the T tube. Diagnosis and therapy of bilhaemia are discussed.


Massive colonic variceal bleeding secondary to abnormal splenocolic collaterals: report of a case. Even in the absence of demonstrable esophagogastric varices in the cirrhotic patient, a diagnosis of variceal bleeding from unusual sites should be entertained in the differential diagnosis of massive lower gastrointestinal hemorrhage. The varices may reflect the increased pressure in the superior or inferior mesenteric systems or in the splenic system through abnormal splenocolic anastomoses. This case has the unique feature of bleeding from varices interposed between the splenic and inferior mesenteric venous systems, as opposed to the previously described cases of varices draining directly into a portosystemic conduit.


[Treatment of complications after endoscopic papillotomy (author's transl)]. In 717 endoscopic papillotomies there were 52 complications in 48 patients, requiring 15 emergency operations with 11 deaths. Surgical intervention was undertaken in six patients for cholangitis after obstruction by stone, in four for retroperitoneal perforation, in two each for bleeding or jamming of the dormia basket, and in one for pancreatitis. Cause of death was very poor general condition or age over 80 years in four; retroduodenal abscess in four; haemorrhagic pancreatitis in two, and cholangiogenic sepsis in one.


Calcium-dependent inhibition by prostaglandin E1 of spontaneous acetylcholine release from frog motor nerve. PGE1 (10(-7) M) in the absence of Ca2+ or at low external Ca2+ concentrations (0.2-0.5 mM) depressed the frequency of miniature end-plate potentials (m.e.p.p.s) in frog sartorius muscle, but m.e.p.p. amplitudes were unchanged. Both an increase in Ca2+ concentration to 2 mM or a blockade of Ca2+ uptake into mitochondria by metabolic inhibitors (5 X 10(-5) M 2,4-dinitrophenol or 2 X 10(-5) M rotenone) prevented the inhibitory action of PGE1 on m.e.p.p. frequency. We suggest that PGE1 may inhibit acetylcholine release from motor nerve terminals by promoting the active uptake of Ca2+ by mitochondria, or by facilitating the efflux of Ca2+ from the axoplasm into the extracellular medium.


Sources and nature of granulocyte-macrophage colony stimulating factor in fetal mice. At the earliest stages of fetal hepatic hemopoiesis in CBA mice (11-12 days gestation), colony stimulating activity could be found only in peripheral blood, yolk-sac fluid and media conditioned by yolk-sacs (YSCM). The colony stimulating factor (GM-CSF) from YSCM was able to be concentrated by absorption to DEAE-cellulose and subsequent elution. Titration of this material produced a sigmoid dose-response curve in agar cultures of adult CBA bone marrow cells. Unlike the high proportion of granulocyte colonies stimulated by the GM-CSF from mouse lung conditioned medium, all concentrations of YSCM produced a high proportion of macrophage colonies after 7 days of incubation. Mixing experiments eliminated the possibility that a specific inhibitor preventing granulocyte differentiation was present in YSCM. Fetal liver cells were relatively unresponsive to YSCM, but their ability to respond increased with gestational age. When stimulated by YSCM, fetal liver colony forming cells from mice of all gestational ages produced more than 90% macrophage colonies after 7 days of incubation. The experimental data suggest that the proliferation and differentiation of granulocyte and macrophage precursors in the early fetal liver could be controlled by a fetal type of GM-CSF favoring macrophage production.


Binding of colony stimulating factor by sterile filtration membranes. Loss of serum-free L-cell colony stimulating factor (CSF) activity was noted when non-sterile or ethylene oxide sterilized Millipore filters were employed; autoclaved membranes showed no inactivation. The reduction in CSF did not appear to be due to release of inhibitory or inactivating substances as extensive rinsing with various solvents did not prevent loss of CSF activity. In addition, these filtrates did not inhibit the activity of standard CSF. Less pure sources of CSF, including standard serum containing L-cell CSF and human urinary concentrate, did not lose activity upon filtration. Moreover, the addition of bovine serum albumin to serum-free CSF completely prevented membrane filtration loss. The CSF loss could be prevented by treatment of the membranes with buffers contraining 0.05% polyethylene glycol (PEG). These findings show that Millipore membranes can bind significant quantities of partially purified CSF. It is important in purification studies to recognize that CSF loss can be prevented by addition of PEG to all buffer systems.


Differences in the buoyant density characteristics of murine granulocyte-macrophage progenitor cells cloned in the presence of serum and/or hemolysate. Bone marrow-derived progenitor cells of granulocytes and macrophages undergo proliferation and maturation in vitro in the presence of colony-stimulating factors and suitable sera. It has recently been found that rat hemolysate can replace serum as a source of growth-supporting activities for cloning these progenitor cells. It is unclear, however, whether serum or hemolysate allows the growth of separate or identical precursor cell subpopulations. Granulocyte-macrophage progenitor cell populations cloned in either serum or hemolysate were identical in their buoyant density characteristics. However, an additional population of granulocyte-macrophage progenitors was preferentially detected when both substances were added to the cell cultures. Different responding cells may, therefore, differ in their nutritional requirements for in vitro cloning. Variability in the respective amounts of these growth factors in the stimulator source would influence the number of CFU-C cloned. The actual amount of stimulator in unpurified sources may, therefore, be grossly overestimated.


Hemopoietic effects in mice of a transplanted, granulocytosis-inducing tumor. A transplanted tumor that induces granulocytosis and produces colony stimulating factor (CSF) was studied in mice during several passages. The sequence of events leading to granulocytosis was characterized. Band granulocytes were increased 3 days after tumor inoculation, while simultaneously CFU-s and CFU-c in bone marrow and spleen were transitorily low. This was followed by rapid accumulation of CFU-c and CFU-s in spleen, and by successive waves of increased mitotable and non-mitotable granulocytes in spleen and marrow. In contrast, marrow CFU-c and CFU-s remained normal or slightly decreased.


EA-rosette-forming cells in chickens: presence in spleens of bursectomized chickens and relationships to B-lymphocytes. Spleen cells from 3-month-old chickens which had been surgically and chemically bursectomized were examined for rosette-forming lymphocytes (RFL). Finding no correlation between the degree of agammaglobulinemia in bursectomized chickens and the percentage of RFL in their spleens demonstrated a dissociation between two B-cell dependent functions, namely, immunoglobulin production and rosette-forming ability. In fact, the percentage of RFL in the spleens of agammaglobulinemic chickens was found to be slightly higher than those of normal chickens. The data indicate that RFL in spleens of normal chickens are B cells, and suggest the existence of a population of rosette-forming B lymphocytes in agammaglobulinemic bursectomized chickens.


The spontaneous shedding of the lymphocyte receptor for sheep red blood cells. Cells in vitro constantly synthesize and shed macromolecules into the surrounding culture medium. B and T lymphocytes also synthesize and shed membrane components. The human T lymphocyte is identified by its ability to attach spontaneously to sheep erythrocytes. This binding is more stable at 4 degrees C and is diminished at 37 degrees C, suggesting that the receptor for sheep erythrocyte may be spontaneously shed at 37 degrees C. Therefore supernatants were obtained from human lymphoyctes at 37 degrees C and then added to sheep erythrocytes at room temperature. After washing, these sheep erythrocytes were unable to rosette with human lymphocytes. The potency of the rosette blocking activity in the supernatant was (a) highest when lymphocytes wereincuated at 37 degrees C, less at room temperature, and least at 4 degrees C, (b) increased by increasing the numbers of lymphocytes held at 37 degrees C, (c) disappeared at dilutions of the supernatants greater than 1:8, (d) was completely adsorbed by sheep erythrocytes. This suggests that lymphocytes spontaneously shed receptors for sheep erythrocytes at 37 degrees C.


The characterization of somatostatin-like immunoreactivity in human serum. We describe the characterization of somatostatin-like immunoreactivity (SRIF-LI) found by radioimmunoassay (RIA) to be present in normal human serum. Degradation by serum of 125I-Tyr1 SRIF in the assay, as assessed by chromatoelectrophoresis and immunoprecipitation, was overcome by using EDTA in the assay buffer and Trasylol in the blood samples. Serum samples thus obtained from 48 normal subjects revealed a bimodal distribution of SRIF-LI; 92 per cent (group 1) had a mean level of 0.274 +/- 0.009 ng. per milliliter. What was measured in these sera showed identity to synthetic SRIF on serial dilutions, Sephadex G-25 chromatography, and thin-layer chromatography, and it was shown to be immunoreactive by an antibody-Sepharose affinity system. Higher levels (1.0 +/- 0.041 ng. per milliliter) were found in 8 per cent of the sera; 50 per cent of this material behaved identically as serum SRIF-LI from group 1. The remainder proved to be heterogeneous, consisting of two peaks of large molecular weight, both of which shared immunologic identity with synthetic SRIF as shown by binding to the antibody-Sepharose affinity system. Their further nature is unknown.


[Aorto-coronary by-pass: pre and post-operative ergometric evaluation of 95 patients (author's transl)]. 95 angina patients surgically treated by aortocoronary saphenous vein by-pass, have been studied by comparing the factors limiting the exercise (i.e. muscular exhaustion, angina, electrocardiographic changes), the total work performed, the O2 consumption and the heart rate-arterial pression product. After surgery the incidence of positive effort tests (effort angina and/or ecg evidence of myocardial ischemia) decreased from 79% to 27,4% (p less than 0,001), and the average amount of work performed increased from 2718 to 3504 Kgm (p less than 0,01), the MVO2 from 13,9 to 15,6 cc/min/Kg. (p less than 0,01) and the heart rate-arterial pression product from 206 to 243 (p less than 0,001). The patients who preoperatively were more invalidated (that is able to performe a lasser amount of physical work) presented a more pronounced improvement in comparison with those who had a greater tolerance to exercise. It seems therefore that for these latter patients the bypass grafting surgery should be justified only if a significant increase of life expectancy and reduction of myocardial infarction incidence could be definitely proved. The exercise performance improvement after surgery was statistically significant only in the patients with post infarction or with unstable angina not in those with chronic angina. The perioperative infarction (present in 8,4% of cases) did not show any unfavorable correlation with the result of the late postoperative effort test.


Hepatitis B in hemodialysis patients: significance of HBeAg. Twenty-four HBsAg-positive (HBsAg+) hemodialysis patients were prospectively studied to assess (1) the prognostic value of HBeAg and its HBe1Ag and HBe2Ag components and (2) whether a difference in cellular immune status between HBeAg+ and HBeAg-negative (HBeAg-) patients could be defined. Sixteen patients were HBeAg+ and 8 were HBeAg- initially. After a mean follow-up period of 23.7 months, it was concluded that the initial presence of HBeAg correlated with the persistence of HBsAg because 15 of the 16 HBeAg+ patients were still HBsAg+ at death or last follow-up, whereas 7 of the 8 HBeAg- patients had become HBsAg- at a mean period of 3.8 months. HBe1Ag was consistently present in 15 of the 16 patients when HBeAg was detectable, whereas HBe2Ag fluctuated widely in individual patients over time. No difference in cellular immune status between HBeAg+ and HBeAg- patients could be defined; although both HBeAg+ and HBeAg- patients had a similar decrease in peripheral blood T cells and poor responsiveness to purified HBsAg, both groups of patients had stimulation indices to nonspecific mitogens within the normal range.


On the incidence of unilateral and bilateral colour blindness in heterozygous females. In 303 mothers of colour-blind sons, both eyes were tested with pseudoisochromatic plates and with the anomaloscope. Two hundred thirty healthy normal and 56 colour-blind males served as controls. In good agreement with the expected proportion of homozygotes in our sample, 17 colour-blind mothers were detected. Eight others had difficulty reading pseudoisochromatic plates and were conspicuous at the anomaloscope. In these, both eyes were affected to a very similar, moderate degree. Monocular disturbances of colour vision were not observed in the entire series. Our data suggest that (1) in most (if not all) of the carriers with colour vision impairment, there is no complete lack of normal retina cones, and (2) the proportion of defective retina cones is remarkably similar in both eyes of individual heterozygotes. The latter observation may indicate that at the time of X-differentiation there is a common primordial cell pool for both retinas.


Reliable classification of six Pi M subtypes by separator isoelectric focusing. For the first time, segregation of three common PiM alleles in family material is verified by application of separator isoelectric focusing. A new nomenclature system for the Pi M subtypes is used, whereby the common subtypes are designated according to their physicochemical properties; the most anodal type is called Pi M1, the intermediary one Pi M2, and the most cathodal variant Pi M3 (previously called Pi M2). Pi gene frequencies from Finnish, Dutch and Black populations are presented. The PiM2 allele was rather high in Finns (0.12) but low (0.04) in the West African Bozo. The PiM3 was found with a frequency of 0.13 in Dutch, 0.08 in Finns and 0.02 in Bozo. A previous Finnish sample was retested with the new subtyping method and the six-subtype distribution was found to be in good Hardy-Weinberg equilibrium. The validity of the Pi polymorphism for population genetics, linkage analysis and parentage testing is discussed.


[Photochemotherapy in mycosis fungoides]. Nineteen patients with mycosis fungoides (m.f.), without involvement of lymph nodes and/or internal organs, were treated with oral photochemotherapy (PUVA). After four to five weeks of PUVA therapy (four irradiations/week) complete remission of erythematous and infiltrative plaques occurred; tumorous m.f. lesions also responded to treatment but required longer treatment times. After complete resolution of m.f. lesions the patients were controlled regularly, the observation periods ranging from 6 to 27 months. When recurrences occurred the initial treatment schedule was resumed. Recurrences, more often seen in the tumorous m.f. stage, responded to PUVA equally well as the initial lesions. PUVA therapy of m.f. is thus more effective than conventional UVB-irradiation and less problematic than treatment with cytotoxic agents or ionizing radiation. Present experience indicates that PUVA represents the treatment of choice in early stage m.f.


Characterization and regulation of anthranilate synthetase from a chloramphenicol-producing streptomycete. In Streptomyces sp. 3022a, anthranilate synthetase is composed of two non-identical subunits. The major subunit (molecular weight, 72,000) converts chorismic acid to anthranilic acid, using ammonia as the source of the amino group. The smaller subunit (molecular weight 28,000 to 29,000) confers on the enzyme the ability to use glutamine instead of ammonia as a substrate. In this study, reactivity with glutamine reached its maximum at pH 7.2 to 7.6, whereas that with ammonia increased linearly through pH 9.0 without reaching a maximum. Activity was increased and stabilized by adding glutamine and magnesium chloride to the buffer system. Both activities of the enzyme were inhibited by anthranilic acid and by tryptophan. Synthesis was repressed by histidine, anthranilic acid, tryptophan, and p-aminobenzoic acid. When activity was repressed by anthranilic acid and by tryptophan, there was a concomitant increase in the activity of arylamine synthetase, an enzyme involved in chloramphenicol production. Stimulating arylamine synthetase, however, did not increase antibiotic synthesis.


Malignant mouse melanoma cells do not form tumors when mixed with cells of a non-malignant subclone: relationships between plasminogen activator expression by the tumor cells and the host's immune response. Mouse melanoma clones B559 and B78 are highly tumorigenic when injected into C57BL/6J mice. Tmor formation by these cells is suppressed when they are mixed with nonmalignant bromodeoxyuridine-grown clone C3471 before injection. C3471 cells suppress tumor formation only in immunocompetent hosts; mixtures of B559 and C3471 cells or C3471 cells alone form tumors in antithymocyte serum (ATS)-treated mice. Explants of C3471 tumors grown in ATS-treated mice form tumors in immunocompetent mice, most of which regress. Inability of C3471 or mixtures of C3471 with malignant cells to grow in normal mice, as contrasted with ability to grow in immunosuppressed mice, indicates that host response is involved. Both tumorigenic clones have high plasminogen activator activity, whereas nontumorigenic clone C3471 has none. Mixture of either tumorigenic clone with C3471 cells decreases plasminogen activator in vitro. C3471 tumor explants from ATS-treated mice initially express plasminogen activator, but lose the capacity to express this activity upon prolonged cultivation in vitro. Explants from B559 tumors retain plasminogen activator in long term culture. Close physical contact between C3471 and B559 cells appears essential both for inhibiton of plasminogen activator expression by B559 cells in vitro, and for tumor suppression in vivo. These findings suggest that production of plasminogen activators by tumor cells may play an important role in suppressing the host's immune response locally to an inoculum of syngeneic tumor cells.


[Urinary incontinence after prostate surgery, Clinical, therapeutic and medico-legal aspects (author's transl)]. Operative damage to the sphincter apparatus below the uvula vesicae is the most serious complication of prostatic surgery. Responsible for more or less total urinary incontinence, sometimes associated with dysuria, it is very difficult to repair, whatever the technics now proposed. The psychological and social repercussions of this infirmity, the difficulty or impossibility of its repair explain the importance of the medico-legal problems raised when the surgeon is responsible.


[Surgery of complicated diverticular sigmoiditis. Report of 138 cases (author's transl)]. The authors analyse a series of 138 cases of complicated diverticular sigmoiditis treated surgically. They noted 50% of pyostercoral peritonitis, 32% of persigmoid abscesses, 13% of case of intestinal obstruction, and 5% of cases of fistual or hemorrhage. The overall mortality was 28% and depended mainly more on the surgical management adopted than on the type of complication. In this respect, simple colostomy with drainage of the septic focus had a mortality of 18%. The results suggest surgical operation in two stages, in the form of colonic resection, with, depending on each case, an anastomosis straight away with transverse colostomy or segmental colectomy with bitubular colostomy (Mikulicz procedure) or, in rarer cases, simple colostomy. The authors emphasise the interest of early surgery in sigmoiditis with complications and contrast the mortality of cold surgery which is now about 5% compared with 28% in emergency cases with complications.


Passive immune haemolysis -- a class specific antibody assay for use in the pig. An antibody assay is described based on the principle of complement mediated lysis of sheep red blood cells labelled with antigen. The technique provides a sensitive class specific assay  enabling antibody in all three major immunoglobulin classes to be quantitated independently. The assay may be performed in tubes allowing precise measurement of antibody concentration, or in microtitre plates which provides a rapid estimation of antibody titre.


Amplification of the enzyme-linked immunosorbent assay (ELISA) in the detection of class-specific antibodies. A modification of the standard enzyme-linked immunosorbent assay (ELISA) is described which circumvents the requirement for specifically purified antibodies from which antibody-enzyme complexes are made. The assay utilizes the principle of a soluble anti-alkaline phosphatase immune complex (AP-A-AP) and has been called the amplified ELISA. Methods for preparing and evidence for the specificity of rabbit anti-rat gamma-FC, IgM (mu) and IgA (alpha) are presented. These reagents are used to measure anti-DNP antibodies belonging to classes IgG, IgM and IgA in rat serum. Using antiglobulin and anti-enzyme reagents prepared in guinea pigs, anti-ovalbumin antibodies are measured in rabbit serum. Titration curves are similar when the amplified ELISA is compared to the standard ELISA. A change in slope suggesting an effect of saturation of antigen sites, occurs at the same input antibody concentration for both assays. Determination of the anti-DNP concentration of unknown sera by extrapopulation from titration graphs of a known serum suggests that the value is overestimated, i.e., amplified when the amplified ELISA is used. In addition, the amplified ELISA has an improved ability to detect low levels of antibody. Evidence is presented which illustrates how the use of optimally conjugated DNP-proteins, age of conjugates, and optimal dilutions of secondary antiglobulins and the AP-A-AP reduce non-specific binding in the amplified ELISA. The amplified ELISA is capable of detecting 2.4 ng of antibody to ovalbumin in a one: one million dilution of rabbit serum with high reproducibility and low background.


Contribution of T cell-mediated immunity to the resistance to staphylococcal infection. Abscess formation in nude mice after subcutaneous inoculation of Staphylococcus aureus (S. aureus) was more extensive and prolonged as compared with that in phenotypically normal littermates. Abscess formation in nude mice was augmented markedly by whole-body irradiation. Not only T cell-mediated immunity but also radiosensitive, nonimmune phagocytosis appear to contribute to the resistance against staphylococcal infection.


Clinical and laboratory evaluation of cefamandole in infants and children. Fifty-three infants and children, aged three months to 15 years, were treated with an average daily dose of 100 mg of cefamandole/kg intravenously. Of these patients, 47 had soft tissue cellulitis and six had pneumonia. Primary pathogens, including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae, were isolated from 43 of the 53 patients. Bacteremia was documented in six of the 53 patients. A satisfactory clinical and bacteriologic response to cefamandole was achieved in all cases except on (98%). The only treatment failure occurred in an infant with both periorbital cellulitis and bacteremia due to H. influenzae who developed meningitis while receiving cefamandole; no extravasation of the drug across the blood-brain barrier could be detected in spite of inflamed meninges. In general, the only aberrant effects of cefamandole were the appearance of eosinophilia in 28% of patients and a positive indirect Cooms' test without hemolysis in one patient. Cefamandole showed excellent in vitro activity against 87 ampicillin-resistant strains of H. influenzae. Because it has greater activity than any of the other cephalosporins against this important pediatric pathogen, cefamandole may have particular pertinence in the treatment of infections in infants and young children.


Failure of cefamandole in treatment of meningitis due to Haemophilus influenzae type b. The in vitro activity of cefamandole was determined against 58 isolates of Haemophilus influenzae type b; 47 were beta-lactamase-negative (ampicillin-susceptible), and 11 produced beta-lactamase (ampicillin-resistant). Ampicillin-susceptible strains were susceptible to cefamandole with a median minimal bactericidal concentration (MBC) of 0.4 microgram/ml. Ampicillin-resistant strains had a median MBC of 0.8 microgram/ml. Prior studies have documented these concentrations of cefamandole in cerebrospinal fluid in the presence of inflamed meninges. Three children with meningitis due to H. influenzae type b were treated with cefamandole (200 mg/kg per day), including one child with disease due to an ampicillin-resistant strain. All patients showed clinical improvement during therapy. However, sterility of the cerebrospinal fluid was never achieved in two patients during 72--96 hr of therapy with cefamandole. The third patient relapsed with a recurrence of positive cultures during the seventh day of cefamandole therapy. Therefore, cefamandole does not appear to be a useful agent for treatment of meningitis due to H. influenzae type b irrespective of in vitro susceptibility or evidence of penetration into the cerebrospinal fluid.


T cells specific for hapten-modified self are precommitted for self major histocompatibility complex antigens before encounter with the hapten. The technique of antigen-driven, 5-bromo-deoxyuridine and light suicide has been adapted to eliminate the precursors of cytotoxic effector cells both for alloantigen and for 2,4,6-trinitrophenyl(TNP)-modified stimulator and target cells. Using this technique, the following observations have been made. Precursors of killer cells specific for alloantigen can be suicided independently of precursors of killer cells specific for TNP-modified self cells. The loss of activity during this procedure is not due to either specific or nonspecific suppressor cells, as judged by mixing experiments. With responder cells from F1 animals, it has been possible to show that precursors specific for TNP-modified cells from one parent are suicided independently of precursors specific for TNP-modified cells of the other parent, but only if the parental strains differ in the K and D regions of the H-2 complex. Cells of F1 mice derived from K and D identical, I region different, parental strains were specifically suicided by TNP-modified stimulator cells from either parent. However, the cross-reactive killing of TNP-self targets induced by stimulation with allogeneic cells is not eliminated by first suiciding with TNP-parental cells, suggesting that the precursors of these two types of TNP-self killer cells are different. This is compatible with reported differences in their specificity, as confirmed in this report. Finally, deletion of alloreactive cells by this technique reveals little or no reactivity specific for TNP-modified allogeneic stimulator cells. In summary, these results strongly suggest that recognition of self MHC antigens is preprogrammed in peripheral T cells of normal animals, and is not acquired during the immunization process. They also suggest that cells specific for modified alloantigen are relatively rare in the strains of mice studied.


Immunoregulatory circuits among T-cell sets. I. T-helper cells induce other T-cell sets to exert feedback inhibition. These experiments test the hypothesis that cells carrying the Ly1+23- surface phenotype are programmed exclusively for helper and not suppressive activity regardless of external conditions such as the mode or type of antigen stimulation. To this end, we have stimulated purified populations of Ly1 cells with antigen in vitro using conditions devised to induce unselected T cells to express optimal levels of antigen specific T-suppressor activity. We find that after such stimulation, Ly1 cells generate SRBC-specific T-helper activity but not T-suppressive activity. These findings establish that the Ly1.2+,2.2/3.2- surface phenotype is a stable, and probably invariant, marker of T cells that are programmed to express only helper activity and have lost the capacity to directly suppress the antibody response. These findings support the concept that the genetic program for a single differentiated set of cells combines information for cell surface phenotype and function. We also demonstrate that antigen-stimulated Ly1 cells, in addition to inducing B cells to secrete antibody, can induce or activate other sets of resting T cells to develop profound suppressive effects. The surface phenotype of this feedback suppressive T-cell set is shown to be: Ly1+2+3+Qa1+. These findings, taken together, indicate that activation of resting Ly123 cells by immune Ly1 TH cells may represent an important homeostatic immunoregulatory mechanism.


Immunoregulatory circuits among T-cell sets. II. Physiologic role of feedback inhibition in vivo: absence in NZB mice. We have shown that (a) purified T-helper cells induce cells of another T-cell set-, expressing the Ly123+Qa1+ surface phenotype, to exert potent suppressive activity, (b) this T-T interaction plays an important role in regulating in vivo immune responses, and (c) this interaction represents an important barrier to protocols intended to augment the immune status of individuals by adoptive (or active) immunotherapy. Our results also indicate that the Ly123+ T-cell set mediating feedback suppression in vivo is sensitive to both low doses of cyclophosphamide and removal of the thymus in adult life. The importance of this T-T interaction to normal, physiologic regulation of the immune system is emphasized by the finding that the major T-cell deficit of NZB mice (an inbred strain of mice that spontaneously develops an autoimmune disorder) is the absence or malfunction of an Ly123+ T-cell set responsible for feedback inhibition.


Restricted helper function of F1 hybrid T cells positively selected to heterologous erythrocytes in irradiated parental strain mice. I. Failure to collaborate with B cells of the opposite parental strain not associated with active suppression. Unprimed (CBA X C57BL/6)F1 lymph node T cells were transferred with sheep erythrocytes (SRC) into heavily irradiated F1 or parental strain mice and recovered from thoracic duct lymph or spleens of the recipients 5 days later. To study their helper function, the harvested F1 T cells were transferred with antigen into irradiated F1 mice plus B cells from either the two parental strains or from F1 mice. F1 T cells activated in F1 mice gave high IgM and IgG anti-SRC responses with all three populations of B cells. By contrast, F1 T cells activated in mice of one parental strain collaborated well with B cells of this strain, but poorly with B cells of the opposite strain. Active suppression was considered an unlikely explanation for this result since (a) good responses were found with F1 B cells, and (b) addition experiments showed that the poor response with B cells of the opposite parental strain (which was equivalent to that produced by unprimed F1 T cells) could be converted to a high response by a supplemental injection of F1 T cells activated in F1 mice. The phenomenon (a) was specific for the antigen used for activation (criss-cross experiments were performed with horse erythrocytes), (b) was reflected in levels of serum hemagglutinins as well as in numbers of splenic plaque-forming cells, (c) applied also to comparable activation of (DBA/2 X C57BL/6)F1 T cells, and (d) could be prevented by activating F1 T cells in mice of one parental strain in the presence of peritoneal exudate cells of the opposite parental strain. The hypothesis was advanced that F1 T cells contain two discrete subpopulations of antigen-reactive cells, each subject to restrictions acting at two different levels: (a) during T-macrophage interactions and (b) during T-B collaboration. It was suggested that when F1 T cells are activated to antigen in a parental strain environment, radioresistant macrophages activate only one of the two subgroups of T cells, and this subgroup is able to collaborate with B cells of the strain used for activation (and with F1 B cells) but not with B cells of the opposite parental strain. The other subgroup of T cells remains in an unprimed (nonactivated) state.


Restricted helper function of F1 hybrid T cells positively selected to heterologous erythrocytes in irradiated parental strain mice. II. Evidence for restrictions affecting helper cell induction and T-B collaboration, both mapping to the K-end of the H-2 complex. Studies with H-2-congenic and recombinant strains showed that when F1 hybrid T cells were activated to sheep erythrocytes in irradiated mice of parental strain or related strain, a population of helper cells was generated which collaborated only with B cells sharing the K-end of the H-2 complex with the strain used for activation. No evidence was found that the restriction in helper function (a) reflected a deficiency of appropriate macrophages during T-B collaboration, or (b) was influenced by the Ig allotype of the B cells. It was concluded that the results signified restrictions acting at both the level of helper cell induction (presumed to be a reflection of T-macrophage interactions in the irradiated intermediate hosts) and during T-B collaboration. With (CBA X C57BL/6)F1 cells, the restrictions at each level mapped to the same region i.e. to the left of the I-B subregion. Consequently, one gene (or set of genes) might control restriction at both levels. If so, T-cell recognition of major histocompatibility complex-associated antigen on macrophages and on specific B cells would be either identical or very similar. The fact that genes mapping to the K-end of the H-2 complex also control the restrictive interactions of homozygous T cells implies that F1 T cells behave functionally as a mixture of T cells derived from the two parental strains. Positive selection to antigen in parental strain mice appears simply to alter the ratio of these two populations.


Effect of colchicine on the antibody response. II. Demonstration of the inactivation of suppressor cell activities by colchicine. The simultaneous administration of colchicine (CC) with a T-independent antigen, e.g. 2,4,6-trinitrophenyl-keyhold limpet hemocyanin-Sepharose, to intact animals effectively enhanced their hapten-specific plaque-forming cell (PFC) response. However, in congenitally athymic nude mice in which T-cell regulation was absent, CC was ineffective in producing enhancement. These observations suggest that the target cell acted upon by CC is most likely thymus-derived. Furthermore, the injection of CC with the co-polymer of L-glutamic acid50-L-tyrosine50 (GT) abolished GT-specific suppression of the PFC response to GT-methylated bovine serum albumin. Spleen cells from CC-treated and GT-primed hosts could no longer transfer suppressive activity to normal recipients. These results provide evidence that CC is capable of inactivating or eliminating suppressor cells or their precursors. Thus, CC-induced enhancement of the antibody response may be explained, at least in part, by its antimitotic, and hence lethal effect on dividing suppressor T cells.


Role of viral infectivity in the induction of influenza virus-specific cytotoxic T cells. This report examines the requirement for infectious virus in the induction of influenza virus-specific cytotoxic T cells. Infectious influenza virus was found to be highly efficient at generating both primary and secondary cytotoxic T-cell response in vivo. Inactivated influenza virus however, failed to stimulate a detectable cytotoxic T-cell response in vivo even at immunizing doses 10(5)-10(6)-fold higher than the minimum stimulatory dose of infectious virus. Likewise inactivated virus failed to sensitize target cells for T cell-mediated lysis in vitro but could stimulate a specific cytotoxic response from primed cells in vitro. Possible requirements for the induction of virus-specific cytotoxic T-cell responses are discussed in light of these observations and those of other investigators.


Expression of Ly 1, Ly 2, Thy 1, and TL differentiation antigens on mouse T-cell tumors. Transplanted lymphomas, most of thymic origin, induced in BALB/c mice with 1-ethyl-1-nitrosourea (ENU) and transplanted spontaneously occurring lymphomas of AKR mice were examined for the expression of the T-cell antigens Ly, TL, and Thy 1 by using three serological methods. Most (11 of 13) of the Thy 1+ and/or TL+ tumors, i.e., T-cell tumors, expressed high levels of either Ly 1 or Ly 2 antigen, but not both. Thus most thymic lymphocytic tumors expressed restricted Ly phenotypes comparable to phenotypes previously described for functional peripheral T cells. Because tumor phenotypes were stable over a number of transplant generations, they therefore appeared to be an intrinsic property of the specific tumors. The majority of the BALB/c lymphomas were Ly 1- 2+ and also positive with anti-TL antiserum. This predominant phenotype on the BALB/c tumors may be related to either the mode of tumor induction or to the mouse strain, but since the restricted Ly pattern was observed both in BALB/c and AKR tumors, the phenotypic restriction itself is not a consequence of either of these factors. Tumor induction by ENU per se is not responsible for Ly or TL ,ntigen expression since several non-T-cell BALB/ c tumors, also induced by ENU, did not express either Ly or TL antigens. Data presented here suggest that the target cell for leukemogenesis may be a partially differentiated thymus cell. The restricted expression of Ly antigens on differentiating thymus cells to either the (formula: see text), phenotype may occur before the loss of TL antigen.


Cytotoxic T cells recognize male antigen and H-2 as distinct entities. XX cells from XX/XY hemopoietic chimeras do not express male determinants in a way to render them either stimulators or targets for male-specific cytotoxic lymphocytes. XX- but not XY-responder T cells from chimeras can be activated to lyse allogeneic male target cells; T cells from normal XX mice depleted of alloreactive T cells, however, cannot be sensitized to lyse allogeneic XY targets. The results imply that T cells recognize the Y-antigen and H-2 as distinct entities, and that in chimeras, they acquire the potential to react against allogeneic XY cells.


Expression of IgD by murine lymphocytes. Loss of surface IgD indicates maturation of memory B cells. B lymphocytes capable of generating primary IgM and IgG plaque-forming cells (PFC) responses to burro erythrocytes have surface IgD, as do primary IgM PFC. IgG memroy cells arising after one injection of antigen are divided into two groups, one of which expresses surface IgD while the other has no detectable membrane IgD. PFC generated from the IgG memory cells lacking surface IgD show a higher average avidity than those arising from IgD-positive IgG memory cells, indicating that mature IgG memory cells do not have surface IgD. After more than one injection of antigen, few, if any, IgG memory cells have surface IgD. IgG PFC arising in primary or secondary immune response lack membrane-bound IgD. These data provide the outlines for a B-cell maturation pathway in which IgD marks unprimed and early memory B cells and is lost in mature memory cells. Studies presented here were conducted by isolating IgD+ and IgD- cells with the fluorescence-activated cell sorter and functional testing of the isolated populations in adoptive transfer experiments.


The relationship between surface immunoglobulin isotype and immune function of murine B lymphocytes. III. Expression of a single predominant isotype on primed and unprimed B cells. We determined whether primed and unprimed B cells in the spleen of (BALB/c x C57BL/Ka)F(1) mice contain subpopulations that express a predominant surface Ig isotype. Spleen cells were stained for surface isotypes and sorted on the fluorescence-activated cell sorter (FACS) in order to obtain B cells bearing predominantly IgM (mup cells), IgD (deltap cells), or IgG (gammap cells). Each population was assayed for its capacity to restore the adoptive primary and secondary anti-bovine serum albumin (BSA) antibody response in irradiated syngeneic recipients. In addition, the adoptive response restored by isotype-predominant cells was compared to that restored by isotype- positive cells (B cells bearing a given surface isotype alone or in combination with others). The experimental results show that mup cells restore the adoptive primary and secondary IgM and IgG responses to BSA, and gammaP cells restore only the primary and secondary IgG response. Deltap Cells restored the adoptive secondary IgG response, but failed to restore the adoptive primary response at the cell doses tested. GammaP Cells but not deltap cells suppressed the IgM response of the mu(+) and delta(+) cells. The contribution of isotype-predominant cells to both the adoptive primary and secondary anti-BSA response was smaller than that of B cells bearing a combination of surface isotypes. Differences in the Ig isotype pattern expressed on the surface of primed and unprimed B cells are discussed.


Morphological and histochemical analyses of two human T-cell subpopulations bearing receptors for IgM or IgG. Two subpopulation of circulating human T cells forming rosettes with neuraminidase-treated sheep erythrocytes were purified on the basis of the presence of receptors for IgG (TG cells) or for IgM (TM cells), and were shown  to have distinguishing morphological and histochemical characteristics. TM cells had the general features of typical small- or medium-sized lymphocytes; most were easily identifiable by distinctive cytoplasmic accumulations, usually one and sometimes two large spots, of nonspecific acid esterase activity. The release of the vesicular contents on short-term culture of TG cells was inhibited by cytochalasin B. Definition of these distinguishing characteristics of TM and TG cells provides a basis for practical enumeration of these functionally distinct subpopulations of human T cells. Some of the TG cells were capable of endocytosis of IgG antibody-coated erythrocytes.


Cell surface glycoproteins of murine cytotoxic T lymphocytes. I. T 145, a new cell surface glycoprotein selectively expressed on Ly 1-2+ cytotoxic T lymphocytes. T lymphocytes at various stages of maturation and differentiation have been isolated by cellular fractionation procedures and characterized by cell surface markers and functional assays, The cell surface glycoproteins of the various T-cell preparations have been selectively radiolabeled by the galactose oxidase-tritiated sodium borohydride technique and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Details are presented on the appearance of a new cell surface glycoprotein (T 145), present on immunocompetent T lymphocytes after activation by either major histocompatibility complex alloantigens or by concanavalin A. The intensity of T 145 expression on T lymphoblasts is shown to be directly correlated in time and extent to the levels of cytotoxicity generated in a variety of T-cell activations. Specific enrichment procedures of purified populations of mixed leukocyte culture blasts have shown Ly 1(+)2(-) blasts to be T 145(-) and Ly 1(-)2(+) blasts to be strongly T 145(+). Similar enrichment procedures on normal peripheral T cells have failed to reveal any significant expression of T 145 on a highly enriched population of Ly 1(-)2(+) T cells, Further studies on the stability of T 145 expression after induction have shown it to be a more permanent-type differentiation structure whose expression is clearly not linked to the blast stage of activation. T 145 would thus appear to represent a membrane glycoprotein whose exclusive expression on T lymphoblasts is further restricted to a defined group of cells endowed with cytolytic activity and bearing the Ly phenotype Ly 1(-)2(+).


Spontaneous pyrogen production by mouse histiocytic and myelomonocytic tumor cell lines in vitro. Tumor-associated fever occurs commonly in acute leukemias and lymphomas. We investigated the capacity for in vitro production of pyrogen by three mouse histiocytic lymphoma cell lines (J-774, PU5-1.8, p 388 D1), one myelomonoyctic line (WEHI-3), and tow lymphoma-derived lines, RAW-8 and R-8. Pyrogen was released spontaneously into the culture medium during growth by all cell lines with macrophage or myeloid characteristics including lysozyme production; R-8 cells, of presumed B-lymphocyte origin, did not produce pyrogen. When injected into mice, the pyrogens gave fever curves typical of endogenous pyrogen, were inactived by heating to 56 degrees C and by pronase digestion, and appeared to be secreted continuously by viable cells. Two pyrogenic molecular species produced by H-774 cells were identified by Sephadex filtration, one of mol wt approximately equal to 30,000, and the other greater than or equal to 60,000. By contrast, three carcinoma cell lines of human origin and SV-40 3T3 mouse fibroblasts did not produce pyrogen in vitro. These results suggest that some malignant cells derived from phagocytic cells of bone marrow origin retain their capacity for pyrogen production, and may spontaneously secrete pyrogen during growth.