Mild phosphate diabetes in adults.

Mild phosphate diabetes in adults. Phosphate diabetes has been considered as rare and to occur almost exclusively in children. Upon examination of adult patients with rheumatic or kidney diseases it has, however, been found that the combination of hypophosphataemia and hyperphosphaturia is not so rare. This paper deals with 24 adult patients of this type, whom we have found during 6 months. Their mean serum phosphorus concentration was 0.7 mmol/l (range 0.5--0.8). Mean phosphate clearance was 31 ml/min/1.73 m2 (range 16--51). The diagnoses were myalgia, dorsalgia (n = 7), papillitis calcificans (n = 5), prostatitis or prostate accretions (n = 4), dizziness (n = 2), kidney stones, tubular defect, interstitial nephritis, medullary sponge kidney (1 case each), two patients had transplanted kidneys. Asthenia was a common additional diagnosis. The patients' complaints have been pain in the muscles, joints, bones (18 cases), tiredness (10 cases), dizziness (8 cases), shakyness, numbness, burning sensation (7 cases), tenderness in the muscles and bones ("the princess-on-the-pea syndrome") (7 cases). The most common findings upon examination were bone tenderness (13 cases), reduced manual power (8 cases), positive Romberg test (3 cases), slight muscle atrophy (2 cases), waddling gait (2 cases). The most common findings encountered in the laboratory, besides hypophosphataemia and hyperphosphaturia, were high pH in the urine, hyperaminoaciduria, and phosphate crystals in dried urine.


[Retrograde positive ventriculography by sub-occipital catheterization of the ventricular system (author's transl)]. The authors describe a new method of retrograde selective ventriculography by means of which the necessity for making an opening in the skull and for a trans-cerebral ventricular puncture is avoided. Trough a sub-occipital puncture and cannula a radio-opaque catheter is guided under radiological control into the ventricular system.


Cytoenzymatic studies on the lymphocytes of peripheral blood and lymphatic nodes of rats in an experimental magnesium deficiency. Wistar rats kept on a magnesium deficient diet show several changes in the lymphatic organs as well as some disorders in the function of the immunological system, which appear as an impairment of cellular immunity and also as hypogammaglobulinemia. In the present experiment the level of leuco- and lymphocytosis has been studied. Furthermore, the activity of some lysosomal enzymes in blood lymphocytes, as well as the ability to incorporate labelled leucine shown by lymph nodes lymphocytes of deficient rats have been investigated. The rise in leuco- and lymphocytosis is similar to that reported by other authors. A significant rise in the activity of beta-glucuronidase as well as a considerable drop in the percentage of enzyme-negative lymphocytes have been observed as early as the first week of experiment. Tissue cultures of the lymph nodes, lymphocytes of deficient rats showed significantly lower values of labelled leucine incorporation with respect to the controls; in contrast, after phytohemagglutinin M stimulation the increase of incorporation in the lymphocytes of deficient and control rats was similar. Our findings may be indicative of some disorders in the redistribution of T and B lymphocytes in the blood and tissues of deficient rats. The observed cytochemical changes may be due to the intensification of autophagic processes in the lymphocytes that manifest a diminished ability to synthetize proteins.


Long term follow-up of aneurysmectomy for recurrent ventricular tachycardia or fibrillation. The success of aneurysmectomy in abolishing recurrent ventricular tachycardia or ventricular fibrillation has not been clearly defined. Ten patients who underwent aneurysm resection to control ventricular arrhythmias were studied before and an average of 19 (4 to 42) months following operation. All patients had moderate to large aneurysms and four had asynergy in adjacent segments. Of four patients with significant stenosis in vessels not supplying the aneurysm, three had aortocoronary bypass grafts in addition to their resection. Ambulatory Holter monitoring and a graded exercise test were performed in all patients postoperatively. There was no operative mortality. Two patients who did not have associated revascularization procedures died suddenly 1.5 and 7 months postoperatively. Of the eight survivors, despite clinical improvement, the Holter ECG revealed runs of ventricular tachycardia in three patients and frequent multifocal ventricular extrasystoles in the other five patients. No correlation was found between recurrence of the ventricular arrhythmias and aneurysm size, contraction pattern of other myocardial segments, extent of coronary disease, or the presence of congestive heart failure. In conclusion, aneurysmectomy does not abolish ventricular tachyarrhythmias and probably should be reserved for patients who remain symptomatic despite an adequate medical trial. The persistence of complex arrhythmias following operation warrants a close follow-up in these patients.


Mechanism of tolerance to DNCB-contact sensitivity induced by immunosuppressive agents. Specific unresponsiveness to DNCB contact sensitivity has been induced in guinea pigs by a combined application of two immunosuppressive agents, cyclophosphamide and antithymocyte serum, to guinea pigs during the period of sensitization with DNCB. This tolerance was specific since the reactivity to an unrelated hapten (oxazolon) was not impaired by the previous immunosuppressive treatment. The unresponsiveness induced by immunosuppressive treatment has not been reversed by an additional treatment with the high dose of cyclophosphamide known to reverse hapten-induced tolerance, and has not been transferred by parabiosis from tolerant to normal partners. From these results it is concluded that specific unresponsiveness induced by immunosuppressive agents is not mediated by suppressor cells but is rather based on clonal deletion. The relative in unstability of this tolerance may be due to formation of new antigen-reactive cells from undeleted precursors.


Thallium-201 myocardial perfusion scintigraphy to evaluate patients after coronary bypass surgery. To determine the utility of thallium-201 stress scintigraphy in assessing the results of coronary bypass surgery, chest pain, stress electrocardiograms and scintigrams were evaluated in 27 patients postoperatively. These findings were compared with coronary angiographic data in which a significant postoperative lesion was defined as 75 percent or more stenosis in a graft, its distal vessel or in an ungrafted native vessel. As an indicator of postoperative coronary lesions, chest pain lacked sensitivity (60 percent) and was nonspecific (20 percent). The stress electrocardiogram had poor sensitivity (60 percent) and good specificity (86 percent) but was not helpful in six patients who had equivocal or suboptimal tests. The scintigram had good sensitivity (77 percent) and was highly specific for the diagnosis of coronary stenosis. It was significantly more specific than chest pain (P less than 0.01), gave excellent localizing information and added to the accuracy of both conclusive and inconclusive stress tests. In nine patients with preoperative stress scintigrams, comparison of pre- and postoperative studies reflected the éffects of bypass surgery on coronary perfusion. Scintigraphy is a useful technique for the noninvasive evaluation of the patient after coronary bypass surgery, and postoperative scintigraphy alone is of great value in documenting surgical results.


T and B lymphocytes in various allergies. The percentages and absolute numbers of T, B and "null" cells were studied in 100 allergic patients and compared with values observed in 35 healthy age matched control subjects. T cells were identified by their ability to form spontaneous rosettes with SRBC (E-RFC) and B cells by their complement receptor that allows the binding of antibody-complement coated erythrocytes (EAC-RFC). The PBL count was found to be slightly lowered in patients suffering from pollinosis, candidiasis and chronic urticaria. The percentages of T and B lymphocytes were similar in both allergic and healthy people, but the patients with pollinosis, candidiasis and chronic urticaria showed decreased absolute numbers of T lymphocytes. Most of them had normal or even--in some cases of pollinosis and candidiasis--increased numbers of B lymphocytes, and normal or--as in some cases of chronic urticaria and candidiasis--increased numbers of B lymphocytes, and normal or--as in some cases of chronic urticaria and candidiasis--decreased numbers of "null" cells. This study support the hypothesis that allergic diseases may be associated with a defect of a subpopulation of T cells, however, it does not seem possible that "null" cells may represent these defective suppressor T cells.


Results of aortocoronary bypass grafting in patients with subendocardial infarction: late follow-up. Twenty-eight patients with subendocardial infarction (Group A) were compared with 28 patients with unstable angina (Group B) and 28 with stable angina (Group C) matched for age and sex. The three groups did not differ in prevalence of diabetes, hypertension, old infarction or duration of disease. There were no significant differences in number of diseased vessels, coronary score, abnormal left ventricular wall motion or left ventricular end-diastolic pressure. Angiograms performed 2 weeks postoperatively revealed closure of 3 of 31 grafts (16 patients) in Group A, closure of 3 of 34 grafts (17 patients) in Group B and closure of 6 of 50 grafts (22 patients) in Group C (differences not significant). Postoperative angiograms showed improved wall motion in 37 percent of Group A, 53 percent of Group B and 36 percent of Group C (differences not significant). Postoperative new Q waves appeared in one hospital in Group A and in two patients in Groups B and C. There were no hospital or late deaths. In a mean follow-up period of 29 months, 68 percent of patients in Group A, 61 percent in Group B and 54 percent in Group C were asymptomatic. Thus, bypass grafting was performed with similarly low mortality and morbidity in patients with subendocardial infarction and in those with angina; more than one third of postoperative angiograms in the three groups showed improved wall motion; and late follow-up studies demonstrated functional improvement in the majority of patients in all three groups.


Intraoperative evaluation of the functional significance of coronary collateral vessels in patients with coronary artery disease. Coronary hemodynamics were studied intraoperatively in 65 patients undergoing aortocoronary bypass grafting. Poststenotic coronary pressure and graft flow hyperemia were measured. Patients without coronary collateral vessels on arteriography (class A) were compared with patients with collateral vessels (class B). Patients in class A were grouped according to the angiographically determined degree of coronary stenosis. Eight of these patients with moderate coronary stenosis underwent intraoperative studies with transient complete coronary occlusion and were classified in the "acute" occlusion group. In class B all patients had complete coronary occlusion with good retrograde filling of the distal segment. In class A patients there was good correlation between the degree of stenosis and poststenotic pressure or hyperemic response. Stenosis had to be at least 80 percent before it produced a significant pressure gradient or graft flow hyperemia. In class B patients (those with complete "chronic" coronary  occlusion), poststenotic pressure was significantly greater than in the class A patients with "acute" occlusion, significantly less than in the class A groups with 71 to 80 percent and 81 to 90% stenosis but not significantly different from values in the class A group with 91 to 99 percent stenosis. The hyperemic response was significantly less than in the "acute" occlusion group of class A, significantly greater than in the class A groups with 71 to 80 percent and 81 to 90 percent stenosis, but not significantly different from values in the class A group with 91 to 99 percent stenosis. It is concluded that (1) under basal conditions a coronary stenosis must be at least 80 percent to be hemodynamically significant, and (2) well developed collateral vessels produce in a completely occluded coronary artery hemodynamic changes that simulate those of a 90 percent coronary stenosis without collateral vessels.


Electrophysiologic effects of acute myocardial infarction in man. Six patients undergoing surgery for ischemic heart disease were studied by means of epicardial electrodes affixed to the left ventricle. One patient who underwent triple coronary arterial bypass and plication of a left ventricular aneurysm had evidence of an acute myocardial infarction 1 day after operation. A surface electrocardiogram and a bipolar electrogram from the left ventricle were recorded before and after development of the infarction. The bipolar electrogram showed a marked loss of voltage and delay of conduction that were not present in the  patients who underwent surgery but did not sustain an acute myocardial infarction. Thus, any acute myocardial infarction in conscious persons appears to be associated with areas of delayed epicardial action and diminution of local voltage. This observation suggests that the electrophysiologic mechanisms of infarction in man are similar to those of infarction in the dog.


Spread of Haemophilus influenzae. Secondary illness in household contacts of patients with H influenzae meningitis. To determine the risk of severe secondary illness in household contacts of patients with Haemophilus influenzae meningitis, telephone interviews were conducted with contacts of patients with reported cases. Four probable or proved secondary cases of severe disease were identified for a secondary attack rate of 0.4%. The secondary attack rate for household contacts of patients 2 years of age and younger was 4.9%. Until safe, effective prophylactic measures become available, physicians should explain to parents that any person who becomes ill in the month after a household case of H influenzae meningitis should be brought to the attention of a physician for appropriate evaluation and treatment.


Oral administration of chymotrypsin labile peptide for a new test of exocrine pancreatic function (PET) in comparison and pancreozymin-secretin test. A new test using N-benzoyl-L-tyrosyl-p-aminobenzoic acid (N-BT-PABA) for an evaluation of exocrine pancreatic function was compared with a pancreozymin-secretin test in 38 subjects. Urinary recovery of PABA, which is absorbed from the intestine and conjugated in the liver after an oral administration of N-BT-PABA, depends mainly on chymotrypsin activity. The recovery rate of PABA in urine decreases in chronic pancreatitis, in which chymotrypsin activity in the duodenal juice is disturbed. The recovery rate of PABA in calcifying chronic pancreatitis was 40.2 +/- 15% and significantly less than 81.2 +/- 7.4% in normal subjects (P less than 0.01). The amount of PABA in urine during eight hours was correlated with parameters of volume output- bicarbonate concentration and amylase output stimulated by injections of pancreozymin and secretin (P-S test). The new test using N-BT-PABA is useful for the evaluation of exocrine pancreatic function in general practice.


Recurrent renal carcinoma causing intestinal hemorrhage. Three cases of gastrointestinal bleeding caused by secondary renal carcinoma are presented. Hemorrhage occurred secondary to invasion of bowel anatomically related to the primary tumor. Bleeding can best be controlled by excision of tumor and involved intestine. Surgery is justified by the unpredictable prognosis for renal carcinoma with secondary disease.


Endoscopic evaluation of upper gastrointestinal bleeding in the newborn. A case of upper gastrointestinal bleeding in the first 24 hours of life is discussed. The application and importance of upper gastrointestinal fiberoptic endoscopy in establishing a precise diagnosis in this age group, not previously reported, is demonstrated.


Acquired von Willebrand's disease, platelet-release defect and angiodysplasia. A previously healthy elderly man with gastrointestinal bleeding was found to have criteria for von Willebrand's disease. The late clinical onset of the disorder and negative family studies suggest that the von Willebrand's disease may be acquired. The findings in the patient were similar to the abnormalities reported in the small number of other patients thought to have acquired von Willebrands disease. An inhibitor of factor VIII could not be demonstrated in this patient. This patient also had platelet aggregation abnormalities that are atypical for patients with congenital or acquired von Willebrand's disease. Vascular abnormalities were also found in this patient and in several other previously described patients with von Willebrand's disease.


Scanning electron microscopy of intraocular lens and endothelial cell interaction. Scanning electron microscopic evaluation of two intraocular lenses removed at keratoplasty for pseudophakie bullous keratopathy demonstrated apparently viable endothelial cells adherent to their surfaces. These presumably adhered to the lens implants at the time of their insertion and confirm this as a mechanism for endothelial damage and subsequent corneal edema from intraocular lens implantation.


Bacterial cultures of lenses removed during cataract surgery. Lenses removed in 408 cataract operations were cultured for bacteria. Most (78%) lenses were sterile. Of the positive cultures, 48% were positive for Staphylococcus epidermidis and 15.4% for S. aureus. These findings reflect the flora of the normal preoperative conjunctiva, and the organisms most commonly implicated in postoperative endophthalmitis. One case of endophthalmitis occurred in this series, and S. aureus was cultured from the lens and later from the postoperative wound and a wound suture, but no intraocular paracentesis was performed to confirm the causative organism.


Septo-optic dysplasia (de Morsier syndrome). A 12-year-old girl and a 30-year-old woman had bilateral optic disk hypoplasia and bitemporal hemianopia. By using computed axial tomography on our patients, we demonstrated the absence of the septum pellucidum, which confirmed the diagnosis of septo-optic dysplasia, or the de Morsier syndrome.


Venous catheter-associated candidemia.

Venous catheter-associated candidemia. Fifty-five patients with venous catheter-associated candidemia were seen over a 13-year period. Thirty-five patients recovered from the infection. Twenty-six of these patients became afebrile within 72 hours of catheter removal; none were treated with systemic antifungal agents. Endophthalmitis appeared in four patients, three of whom had significant loss of vision. Nine patients had persistent candidemia following catheter removal and required antifungal therapy; none developed metastatic infection. Twenty other critically ill patients died during fungemia. Two of these patients were found to have Candida endocarditis that arose from previous catheter infections not suspected of being caused by this organism. Prevention of candidemia by proper care of indwelling vascular catheters is the ultimate goal. Appropriate management of the episodes of candidemia that occur may avert serious metastatic complications.


An animal model for childhood convoluted T-cell lymphoma. The light microscopic and ultrastructural characteristics of the AKR-J mouse lymphoma are described in detail. Clinical and histologic facets of convoluted T-cell lymphoma of childhood and AKR-J mouse lymphoma are reviewed. The remarkably close correlation between these two entities is demonstrated. The possibility that this mouse tumor should be utilized as a model for convoluted T-cell lymphoma of childhood is emphasized.


Renal and vascular responses of the bullfrog (Rana catesbeiana) to mesotocin. Although mesotocin (MT) has long been known to occur in the amphibian neurohypophysis, there have been few reports on its action among amphibians. In the present investigation, renal responses of intact bullfrogs (Rana catesbeiana) and perfused bullfrog kidneys to MT were studied. The blood pressure responses of this amphibian to MT were also analyzed. We found that MT is diuretic at low doses and that the response is dose related. At high doses the diuretic response decreases progressively and, at times, antidiuresis is observed. The changes in urine flow are proportional to the changes in glomerular filtration rate. In addition, there is a dose-related depressor effect. Data from perfused kidney studies suggest that MT may dilate the afferent glomerular vessels. The possible action of MT as a physiologically important diuretic agent is discussed.


Immune competence in patients with Klinefelter syndrome. We studied cellular and humoral immunity on ten patients with documented Klinefelter syndrome. Cellular immunity as measured by in vivo skin tests and in vitro lymphocyte transformation tests appeared intact. However, the mean values of T cells and EAC rosette-forming cells were significantly decreased as compared with controls. All patients had normal isoagglutinin titer. One patient failed to produce febrile agglutinin even after immunization. Some patients showed elevated levels of Immunoglobulin G (IgG) or Immunoglobulin M (IgM), probably due to the underlying diseases. Three patients had serum and secretory Immunoglobulin A (IgA) levels below normal. Classification of IgA deficiency and its associated diseases were discussed. These three patients are 38, 44, and 60 years old respectively. Long-term follow-up of these three patients can determine whether or not they will develop malignancy and autoimmune diseases. One patient with bronchogenic carcinoma and the other with autoimmune disease had normal serum and secretory IgA levels. It is possible that they had low IgA initially, but their underlying diseases brought up their IgA levels to the normal range.


Lack of association of hepatosplenic schistosomiasis and alpha-1-antitrypsin deficiency. To evaluate the role of alpha-1-antitrypsin deficiency in the pathogenesis of hepatosplenic schistosomiasis, alpha-1-antitrypsin was measured in 90 patients with schistosomal splenomegaly and in 87 phenotyping was also done. All levels were in the normal range except for those of two patients who were shown to have the heterozygous deficiency state, PiMZ. The phenotypes found in the 87 were as would be expected in a normal population. Alpha-1-antitrypsin deficiency does not play a significant role in the pathogenesis of hepatosplenic schistosomiasis.


Meckel's diverticulum. Investigation of 600 patients in Japanese literature. A total of 600 cases, comprising 4 of our cases and 596 others in Japan, was analyzed, and the diagnosis of Meckel's diverticulum was made in only 34 of them. The rate of diagnosis was 5.7 per cent, which is very low. The most common complication of this disease was intestinal obstruction, the second most common was intussusception, the third was inflammation, and the fourth was rectal bleeding. Ectopic tissue, present in ninety-three patients, consisted of ectopic gastric mucosa in fifty-eight. 99mTc-P scanning was performed on fifteen patients. In twelve of them ectopic gastric mucosa was observed. However, it was not found in three, all of whom had false-positive scans.


Diagnosis and management of spontaneous aortoenteric fistulas. Spontaneous aortoenteric fistulas are rare but appear to be increasing. They may occur anywhere from the esophagus to the rectum but most often between the duodenum and an infrarenal abdominal aortic aneurysm. Four patients (two with aortoesophageal, one with aortoduodenal, and one with aortocolic fistulas) are presented. The patient usually presents with the clinical triad of aortic aneurysm, pain suggesting aortic disruption, and gastrointestinal hemorrhage. The final exsanguinating hemorrhage is usually preceded by prodomal hemorrhages of varying severity which may be present for weeks to months. Endsocopy is the most helpful diagnostic procedure. Prompt aggressive surgical therapy is the only hope for survival. Successful reconstruction requires placement of the graft in uninfected tissue--often in an extraanatomic position--and interposition of healthy tissues between the graft and the repaired enteric tract.


Co-activation of the M. transversus auris with eye movements (Wilson's oculo-auricular phenomenon) and with activity in other cranial nerves. Extreme lateral gaze induces a perceptible backward movement of the upper part of the pinna (Wilson, 1908). In 29 subjects (15 normal controls and 14 patients with peripheral eye-muscle or facial paresis) electromyographic (EMG) investigation of the transverse auricular muscle with simultaneous electronystagmographic (ENG) recording of the various ocular movements was carried out. Tonic activity was detected in the transverse auricular muscle during extreme horizontal eye movements, but was detected in only a few subjects during convergent or vertical movement of the eyes, or in the primary position. Investigation of the other cranial nerves revealed that EMG activity of the transverse auricular muscle is also occasionally present during chewing, coughing, swallowing, straining, inspiration, and vestibular stimulation.


[The effect of the pupil as aperture and field stop on the various components of the human electroretinogram (author's transl)]. The electroretinogram (ERG) was recorded in 10 normal subjects under scotopic and photopic conditions with the pupil of one eye constricted and that of the other eye dilated. The human iris, being displaced from the nodal point of the eye, acts not only as an aperture, regulating the retinal illumination, but also as a field stop, limiting the visual angle, especially for large object fields, as in Ganzfeld illumination. This double effect of a constricted pupil clearly influences the Ganzfeld ERG, not only shifting the intensity response functions to higher luminances but also diminishing the maximal responses. Control experiments with smaller test fields, which are less affected by the pupillary field-stop properties, reveal no diminution of the scotopic b-wave amplitudes. Implicit time functions, being nearly independent of the number of receptors stimulated, can be matched by taking into account the pupillary diameter and calculating the actual retinal illumination (Troland). Amplitudes, being highly affected by a decrease of responding neurons due to the angle-limiting field-stop character of the pupil, cannot be matched with regard to the pupillary diameter. This effect is most noticeable in Ganzfeld illumination for the scotopic b-wave, generated mainly by neurons of the peripheral retina, and has less effect on the photopic responses that are generated more centrally.


Changes of the current pathways in the eye due to coating agents during electroretinography. This study suggests a model by which we try to explain why coating agents habitually applied in electroretinography can change the amplitude of electroretinographic responses. The model is based on the results of experiments described in this paper. The accuracy of measurement in clinical and experimental electroretinography can be enhanced by applying this model.


The influence of coating agents on the electrode circuit in electroretinography. In electroretinography, coating agents are usually applied to improve the contact between the contact-lens electrode and the eye. These agents influence electroretinographic responses. In this experimental study we show that the characteristic properties of the electrode circuit are not influenced by the coating agent. Thus we conclude that these coating agents influence the eye itself. The mechanism of this interaction may be physical, or may be an unknown pharmacologic drug side effect.


[Wound healing in the feline retina following mechanical trauma (author's transl)]. The healing of superficial retinal scratches inflicted with a Sato knife was followed from days 1 to 135 in 20 domestic cats. Breakdown of retinal tissue continued for 18 weeks. Glial proliferation was extremely sparse and never observed before day 6. Microvilli and cell processes, derived mainly from Müller cells, were also seen in the wound. Regeneration of the internal limiting membrane was never observed. The choroid, pigment epithelium, retinal blood vessels, and vitreous played no part in the healing process.


Experimental skeletal teratogenesis in the frog tadpole. Severe deformities of the hind limb skeleton such as shortening, abnormal curvatures, terminal expansions, curled toes and joint dislocations were produced in frog tadpoles by the osteolathyrogenic principle. Gross-anatomical features of the deformed skeleton and of the respective nervous trunks were studied in specimens cleared according to WILLIAMS' technique. The findings support the previously suggested osteo-neural concept: Experimental skeletal deformities represent adaptations of the bone growth at the organ level to the inadequate extensive growth of the nervous trunks. The neural growth appears to be more severely affected by the teratogen than the bone growth proper.


Thymic hormones and immunopeptides.

Thymic hormones and immunopeptides. The role of the thymus and its hormones in immunity is discussed. The known characteristics of various thymic factors, their mode of action and possible clinical applications are also reviewed. A brief discussion of other immunopeptides which are liberated by lymphocytes is also included.


Aspirin- and coumadin-related bleeding after coronary- artery bypass graft surgery. We studied 100 consecutive patients to evaluate the potential effect of platelet active and antithrombotic agents prescribed preoperatively on bleeding complications after coronary-artery bypass graft surgery. Preoperative hemostatic values were normal in all patients. Mean mediastinal blood loss was significantly greater in 13 patients taking aspirin (892 +/- 91 ml) and six patients taking Coumadin (warfarin sodium) (858 +/- 168 ml) within 7 days of surgery than in 64 control subjects (439 +/- 28, P less than 0.001). Less marked but similar differences (P less than 0.05) were noted with other agents inhibiting platelet function. However, in nine patients given heparin, mean mediastinal blood loss (436 +/- 61 ml) was no different from that of control subjects. The degree of mediastinal blood loss did not correlate with age, sex, mean total operative time, bypass time, or number of vessels diseased or bypassed. In addition, patients taking aspirin or Coumadin required prolonged chest tube drainage compared to those in heparin or control groups (34 +/- 4 versus 20 +/- 1 h) (P less than 0.001).


[7 cases of trisomy 2q34 leads to 2qter resulting from a familial t(2;8)(q34;23)]. Seven patients from two different families are trisomic 2q34 leads to 2qter due to segregation of a familial t(2;8)(q34;p23). The clinical features are characteristic: microcephaly, a narrow forehead with bossing and temporal retraction, hypertelorism, palpebral fissures slanted downwards, large irides, and a very concave margin of the lower eyelid. Mental retardation is severe with a mean IQ of 50.


[Gene dosage and chromosome enzymatic markers]. Data are tabulated on the number of nomenclature current abbreviations, the occurence of multiple gene loci and corresponding polypeptide chains, and chromosomal assignment of 114 enzymes. Gene dose effect measurement is dependent upon several properties of the enzyme which are also listed: tissue and subcellular distribution, subunit number, interloci hybrids, genetic polymorphism, qualitative and quantitative methods of detection. The possibilities and limits of the concept of a gene-dose relationship, for the detection of carriers of chromosomal aberrations, and also for chromosomal assignment are discussed.


[Anomaly of the nuclear maturation in vitro of golden hamster oocytes]. Nuclear anomalies were observed during maturation in vitro of golden hamster oocytes, as follows: 1) In 33 p. cent of oocytes, the axis of the first meiotic division spindle was oriented incorrectly. This leads either to the formation of "large" polar bodies or to non-expulsion of the polar body if the spindle occupied a central instead of peripherical position. 2) Triploidy was observed in 0.3 p. cent of the oocytes which accomplished their maturation and fertilization in vitro. 3) Two rare anomalies--reconstitution of the nucleus after expulsion of the first polar body and formation of two second division spindles--appeared to be due to degenerescence of the oocytes in culture.


Regulation of immune response by anti-receptor antibody. A new function of antibodies in the regulation of immune responses is proposed. Antibodies have specific variable sequence determinants which are detected by anti-idiotypic antisera. Anti-idiotypic antibodies can suppress the production of the complementary idiotypic  antibody and are, therefore, specific anti-receptor antibodies. Experiments in inbred mice have shown that mutual and reciprocal functional interactions of idiotype and anti-idiotype can occur. These findings give evidence for regulatory mechanisms in the expressions of immune clones by complementary idiotypes.


[Assignment of alpha-Fuc to1p in man and the chimpanzee and to chromosome 4 in the African green monkey]. Analysis of cellular hybrids confirms the assignment of alpha-L-fucosidase (alpha-FUC) to 1p in man. Discordant results are in favour of the following gene order: 1pter (ENO-1, alpha-FUC,AK2) PGM1 centromere Pep-C but give no information on the relative positions of ENO-1,alpha-FUC, and AK2. The assignments of alpha-FUC to chromosome 1 in the chimpanzee and to chromosome 4 in the African green monkey are demonstrated (chromosome nomenclature by Finaz et al, 1976). These results confirm the homology of chromosome 4 of the African green monkey and 1p of man and the chimpanzee.


Another case of 9P-syndrome.

Another case of 9P-syndrome. This paper discusses the value of an International Repository of Chromosomal Abnormalities and Variants as a means of communication and case finding. A further case of 9p- is described. The clinical and cytogenetic findings confirm the existence of a clinical entity which in many respects is the opposite of the 9p trisomy syndrome.


A theory explaining the abnormality in 45,X/46,XY mosaicism with non-fluorescent Y chromosome. presentation of three cases. Three patients with male habitus, short stature and testicular differentiation are described. All had mos 45,X/46,XY, the ratio of the two stemlines varying between the patients and between different tissues. The Y chromosome was abnormal, lacking the brilliant QFQ fluorescence and dark CGB staining characteristic of the distal part of the normal Y. Detailed banding studies suggested that the short arm and proximal part of the long arm were normal, while the distal part of the long arm was molecularly or otherwise altered, resulting in abnormal staining properties. Two of the patients were tested for H-Y antigen and found to be positive. These data and those collected from the literature are compatible with a model in which the primary lesion in X/XY mosaicism is a molecular alteration in the reiterated Y-specific DNA sequences (and possibly neighbouring sequences) of a 46,XY zygote resulting in the frequent mitotic loss of the Y and the emergence of a 45,X line. Provided the testis-determining gene(s) near the centromere are normal, testes are formed and the patient is H-Y antigen-positive. The extent of male or female differentiation depends in part on the prevalence, time of occurence, and distribution of the 45,X line and possibly in part on the alteration of other genes involved in sex differentiation and located on Yq further from the centromere.


A case of partial 9p monosomy with some unusual clinical features. A patient is described with a karyotype 46,XX,del(9)(qter leads to p22:) and having the main clinical characteristics of pure monosomy for part of the short arm of chromosome No 9, among which craniosynostosis and trigonocephaly. She has also a few atypical features: a clearly advanced osseous maturation, marked congenital vertebral anomalies and unusual dermatoglyphics.


A 45,XX,-5,-14,+t(5q;14q)mat cri du chat child. A two-year-old girl has the following features of the cri du chat syndrome: microcephaly, hypertelorism, downward slanting of the palpebral fissures, psychomotor retardation and a cat-like cry. She is only of five patients having the cat cry syndrome with 45 chromosomes. Her karyotype is 45,XX, -5, -14, +t(5; 14)(5qter leads to 5p11: : 14q11 leads to 14qter) with the translocation inherited from her mother and maternal grandmother, each of whom is the carrier of a balanced translocation 46,XX,t(5;14)(p11q11). Normal plasma activity for hexosaminidase B suggests the locus for this enzyme is not located in the delected segment of 5 p.


Partial trisomy 18(q11 leads to qter) in an infant and aborted fetus resulting from a balanced paternal translocation t(13;18)(q32:q11). Partial trisomy 18 is described in a two month old female with severe mental, motor and growth retardation, associated with multiple congenital anomalies characteristic of complete trisomy 18. Trisomy for almost all of 18q resulted from adjacent I segregation of a paternally inherited translocation t(13; 18)(q32:q11). The balanced translocation was observed in three generations of the family. Partial trisomy 18q identical to that observed in the proband was found in a subsequent miscarriage.


Transferable chloramphenicol and ampicillin resistance in a strain of Haemophilus influenzae. A strain of Haemophilus influenzae isolated from sputum has been shown to be resistant to chloramphenicol, ampicillin, and tetracycline. All three resistances were transferred together to recipients when the selecting antibiotic was ampicillin, chloramphenicol, or tetracycline.


Treatment of alopecia areata with dinitrochlorobenzene. Persistent refractory alopecia areata in 26 patients was treated topically with dinitrochlorobenzene (DNCB). Sixteen patients have had excellent regrowth of hair; three patients could either not be initially sensitized or an adequate allergic contact dermatitis on the scalp did not develop. Two patients discontinued therapy within two months; hair growth did not develop in five patients despite an adequate trial. Augmentation of the T-lymphocyte pool via DNCB sensitization and challenge may become effective therapy for some patients with severe alopecia areata.


Infant with abnormal pigmentation, malformations, and immune deficiency. An infant had swirling hyperpigmentation, streaks of hypopigmentation, abnormal T-cell function, cleft palate, patent ductus arteriosus, and arrhinencephaly. This pattern of abnormalities is distinct from other disorders with abnormal pigmentation and malformations; such as incontinentia pigmenti, incontinentia pigmenti achromians, and the epidermal nevus syndrome.


[The special relations of malignant skin lymphomas to the epidermis and to the epidermal appendages (author's transl)]. Epitheliotropia of malignant skin lymphomas is an unexplained phenomenon which equally affects epidermis and ectodermal appendages. This phenomenon is found especially in tumours of probable T-cell origin. However it can also be observed in B-cell lymphomas (immunocytomas) and is therefore not an exact criterium for the biological origin of a lymphoma. In the case of germinal center tumors we could not find evidence of epitheliotropia. An active invasion of neoplastic cellular infiltrate into the epithelium must be differentiated from the phenomenons caused by passive pressure, resulting from the expansion of the tumor. However, one has to remember that epitheliotropic malignant lymphomas invade the epidermis in all stages of development. It is shown, that Pautrier microabscesses are only a special non specific aspect of epidermotropia.


T-cell function in atopic dermatitis. Controlled examination of concanavalin A dose-response relations in cultured lymphocytes. The Concanavalin A (Con A) stimulation response of peripheral lymphocytes in vitro was found to be decreased statistically significant (alpha = 0.005) in patients with light atopic dermatitis, Strictly matched pairs were examined. Using ten graded concentrations of Con A, dose-response relations of the pairs were demonstrated, differences were more evident at lower suboptimal concentrations. Background DNA-synthesis of the patients was elevated.


Combination of theophylline and prostaglandin E1 as inhibitors of the adjuvant-induced arthritis syndrome of rats. The effects of daily subcutaneous administration of prostaglandin E1 (PGE1), theophylline, and of both drugs together were studied on the Freund's adjuvant-induced inflammatory and arthritic syndrome in rats. In the doses used, neither drug affected the acute inflammatory response in the adjuvant-treated paw, but together they caused marked inhibition. Chronic inflammation in the contralateral (nontreated) hind paws was slightly inhibited by each drug and combined treatment resulted in marked inhibition. The drugs also counteracted splenomegaly in adjuvant-diseased rats and their effects on spleen weight paralleled the inhibition of chronic inflammation. Arthritic lesions, as judged by x-rays of tibiotarsal joint destruction in the nontreated paws, were partially prevented by PGE1 alone, but not by theophylline. The combined treatment entirely prevented these joint lesions. PGE1 did not cause an increase in adrenal weight, but enhanced the effect of theophylline on adrenal weight. Only PGE1 improved gait in arthritic rats, simultaneous theophylline treatement having little additional effect. Other workers have found the PGE1 increases intracellular cAMP and that this effect is enhanced by the phosphodiesterase inhibitor, theophylline. We propose that the anti-inflammatory and anti-arthritic effects of combined drug treatment involve cAMP changes in phagocytic cells at the site of tissue injury and in systemic lymphocytes.


Clinical significance of antibodies to soluble extractable nuclear antigens (anti-ENA). Clinical and biological manifestations have been studied in 134 patients whose serum had antibodies to soluble extractable nuclear antigens (ENA). 85 of the patients had anti-RNP antibodies, 18 had anti-Sm antibodies, and 31 had antibodies to one or more soluble nuclear antigen. In all groups, the predominant clinical manifestations were polyarthritis, Raynaud's phenomenon, fever, and skin involvement. Renal disease was less common in those patients with anti-RNP antibodies than in the other patients. Most patients with definite renal disease (13 out of 15) also had circulating anti-DNA antibodies. The final diagnoses in these 134 patients were well defined connective tissue disease in 59; overlap syndromes in 34; a limited clinical syndrome made up of polyarthritis Raynaud's phenomenon--often with swollen fingers--and/or hypergammaglobulin-aemia in 31, and various other clinical conditions in 10.


The visual analogue scale in the assessment of grip strength. The accuracy of information derived from a visual analogue scale has been assessed by comparing the measured grip strength of 100 subjects against their estimate of grip strength scored on a visual analogue scale. There was relatively poor correlation between the measured and assessed values, suggesting that similar inaccuracies may occur when the scales are used to assess subjective phenomena.


Teaching rheumatology to nurses.

Teaching rheumatology to nurses. Seven different types of lecturing technique were assessed in 14 groups of nurses at 2 hospitals. Two lectures in rheumatology were given to each group and a multiple choice questionnaire answered by the nurses immediately after the lecture and 3 months later. A significant amount of knowledge was imparted by the lecturer. About a third of the knowledge, however, was lost within a minute of the end of the lecture, and a half to two-thirds within 3 months. There was no correlation between scores and the row on which the students sat. There was no significant difference between the scores of overseas students and those of British nurses. At immediate recall the techniques differed little. The techniques which scored best were giving the questionnaire before the lectures, giving handouts and using the blackboard. At delayed recall 100% differences in marks were seen between the worst and best techniques in the second lecture. The same techniques which scored best at immediate recall did so on delayed recall. The lowest score occurred where note taking was forbidden. Some questions scored significantly better with note taking. When note taking was forbidden, it made no difference if the student was an habitual notetaker or not. Nor did it make any difference if she was frustrated by the ban. There was no correlation between entry qualifications and the scores obtained. Nurses at a non-teaching hospital did just as well as those at a teaching hospital. It should be emphasised that teaching endeavours to influence 3 aspects-knowledge, skills and attitudes. This series of experiments largely tests the first, but does suggest that a technique which scores highly on information recall may be less helpful in forming constructive attitudes to the patient.


A randomized, controlled trial of the distal splenorenal shunt. In 1971 a prospective, randomized trial was initiated to determine efficacy of the distal splenorenal shunt in the management of cirrhotic patients who had previously bled from esophageal varices. When entry into the trial was terminated in 1976, 26 patients had received the distal splenorenal shunt (selective) and 29 had undergone a nonselective shunting procedure (18 interposition mesorenal, six interposition mesocaval, and five other nonselective shunts). Three operative deaths occurred in each group. Early postoperative angiography revealed preservation of hepatic portal perfusion in 14 of 16 selective patients (88%), but in only one of 20 nonselective patients (5%; p < .001). Quantitative measures of hepatic function (maximal rate of urea synthesis or MRUS and Child's score) were similar to preoperative values in the selective group but were significantly decreased in nonselective patients on the first postoperative evaluation (p < .001 for MRUS; p < .05 for Child's score). Eighty-seven per cent of selective and 81% of nonselective patients have now been followed for three to six years since surgery. Late postoperative evaluation of 29 survivors (12 selective, 17 nonselective) still shows an advantage to the selective group with respect to MRUS, Child's score, and incidence of hepatopetal portal blood flow, but differences are no longer statistically significant. However, if the seven patients with portal flow (five selective; two nonselective) are compared to the 20 with absent portal flow (seven selective; 13 nonselective), the former group has significantly higher values for MRUS (p < .05) and Child's score (p < .025). No patient with continuing portal perfusion has developed encephalopathy as compared to a 45% incidence of this complication in individuals without portal flow (p < .05). No significant differences between selective and nonselective groups have appeared with respect to total cumulative mortality (ten selective; 38%; eight nonselective, 28%), shunt occlusion (two selective, 10%; five nonselective, 18%), or recurrent variceal hemorrhage (one selective, 4%; two nonselective, 8%). Overall, significantly fewer selective patients have developed postoperative encephalopathy (three selective, 12%; 15 nonselective, 52%; p < .001). Therefore, we conclude that the distal splenorenal shunt, especially when its objective of maintaining hepatic portal perfusion is achieved, results in significantly less morbidity than nonselective shunting procedures.


Cerebrovascular response to intracarotid infusion of 5-hydroxytryptophan and L-DOPA  in cats. Intracarotid administration of 5-hydroxytryptophan (10 mg/kg) results in a slight vasoconstriction of cerebral vessels. L-DOPA (20 mg/kg) administered by the same route enhances cerebral blood flow. The effect on cerebral blood flow of L-DOPA (20 mg/kg) following intracarotid 5-hydroxytryptophan (10 mg/kg) administration shows a potentiation of cerebral blood flow response in non-pretreated as well as in nialamide- and reserpine-pretreated cats.


[The deficiency of 17-hydroxylase: a cause of growth and puberty retardation in the girl. One case]. A case of 17-hydroxylase deficiency in a 14 years old girl is reported. She presented with the unique association of hypertension, hypokaliemia, delayed puberty and growth failure. It is suggested that the reduced statural growth starting between 7 and 10 years of age and accompanied by a markedly reduced bone maturation was, at least in part, the consequence of the absence of adrenarche. The secretion rate of cortisol was very low while an increased production of D.O.C. and corticosterone was demonstrated by the elevated levels of their urinary tetrahydroderivatives. A good feminisation and a growth spurt were observed under ethinyl oestradiol substitutive therapy. A progressive normalization of the kaliemia and the blood pressure was obtained with hydrocortisone treatment but long term hydrocortisone therapy appears less satisfactory with easy clinical manifestations of overdosage on the one hand and incomplete maintenance of normal blood pressure of the other hand.


[Parinaud's syndrome indicating imbalanced hydrocephalus in patients with cerebrospinal fluid shunts]. The cases of two patients with hypertensive hydrocephalus and Parinaud syndrome are reported. In both cases the ventriculographic studies showed a cystic expansion of the suprapineal recess. The upward gaze palsy was related with the expansion of the suprapineal recess. The radiological study of the posterior portion of the third ventricle in these cases is recommended. The use of inadequate devices in these situations may cause the worsing of the patient.


Haemophilus influenzae cellulitis.

Haemophilus influenzae cellulitis. Cellitis that is caused by Haemophilus influenzae demonstrates a unique predilection for the faces of young children. Although previously considered a rare entity, it is currently being recognized more frequently. Despite the importance of early recognition and treatment in preventing potentially fatal complications, it has been noticeably neglected in the otolaryngologic literature. We report a case and discuss the diagnosis and management of H influenzae cellulitis.


T lymphocytes in the effusions of secretory otitis media. Smears were made from 39 middle ear effusions in 29 children with secretory otitis media (SOM) and stained with acid alpha-naphthyl acetate esterase (ANAE) to demonstrate T lymphocytes. The effusions showed on the average 21% of the lymphocytes to be ANAE positive, while simultaneously drawn peripheral blood revealed the proportion of ANAE positive cells to be 53% (P less than 0.001, the Student's t-test). Our finding suggests that T cell dependent defence mechanisms may be locally disturbed in SOM.


Chemical composition in various compartments of inner ear fluid. Sodium, potassium, chloride, glucose and total protein were determined in samples of scala vestibuli perilymph, scala tympani perilymph, CSF, cochlear endolymph and utricular endolymph from normal cats. Small but significant differences were evident in the concentrations of sodium and potassium between the scala vestibuli and scala tympani perilymph. It was also apparent that each compartment of endolymph has different values for sodium and potassium concentrations. Compared with the endolymph, the perilymph was found to contain a higher concentration of glucose and total protein. These findings are discussed from the view point of biological significance.


Structural studies of wheat monomeric and dimeric protein inhibitors of alpha-amylase. Two wheat monomeric protein inhibitors of alpha-amylase with mol.wt. 12000, designated inhibitors 0.28 and 0.39 according to their gel-electrophoretic mobilities, showed almost identical circular-dichroism spectra in both the far and near u.v. at different pH values as well as in the presence or absence of dissociating and reducing agents. Both inhibitors (0.28 and 0.39) were readily inactivated by reduction of the five disulphide bridges present in each inhibitor molecule. These properties are very similar to those exhibited by the wheat dimeric protein inhibitor of alpha-amylase with mol.wt. 24000, designated inhibitor 0.19 according to its gel-electrophoretic mobility. The N-terminal sequence of the 0.19 inhibitor was determined without separating its subunits and compared with that of the 0.28 inhibitor reported by Redman [(1976) Biochem. J. 155, 193--195]. Petide 'maps' from tryptic digests of reduced and carboxymethylated inhibitors 0.19 and 0.28 were compared. One molecule of reducing sugar is covalently bound per inhibitor-0.19 protomer and inhibitor-0.28 molecule. The results obtained strongly support previous findings indicating the structural equivalence of inhibitor 0.28 with each inhibitor-0.19 protomer and the common phylogenetic origin of these protein alpha-amylase inhibitors from wheat kernel.


A cross-bridge model for inotropism as revealed by stiffness measurements in cardiac muscle. Stiffness measurements obtained by means of rapid length changes performed according to Huxley and Simmons (23) showed that the series elasticity of the living frog myocardium obeys Hooke's law and alters in proportion to isometric tension. The same results had previously been reported for glycerol-extracted heart muscle (15, 16). Under conditions of postive inotropism caused by application of noradrenaline, adrenaline or increased extracellular Ca++ concentration, the proportionality between tension and stiffness is maintained (13). As there is strong evidence that the series elasticity of heart muscle resides in the cross-bridges (17, 24) this means that systolic force development and positive inotropism are due to the same process, namely a recruitment of "activated" cross-bridges (an increase in the number of cross-bridges attached to actin at any moment). This rules out the two-component model proposed by Sonnenblick in which a non-linear series elastic element was postulated.


[Diagnosis of IIIrd ventricular cyst with "amipaque (metrizamide) CT ventriculography (author's transl)]. The patient is a 17-year-old female. She was suffering from dwarfism, irregular menstruation and obesity. Out of the dwarfism, there were no other neurological abnormalities. The serious clinical examinations were performed, and the cerebral angiography and the CT scan demonstrated the findings of the obstructive hydrocephalus. Namely, enlarged IIIrd ventricle and small IVth ventricle were observed with routine CT scan. Because these findings on CT scan, we thought the hydrocephalus was based on the aqueductal stenosis. The vertebral angiography showed stretched posterior medial choroidal arteries and compressed the basilar tip posteriorly and inferiorly. Moreover, the carotid-angiography demonstrated the following findings, unrolling of the anterior cerebral arteries laterally stretched bilateral lenticulostriate arteries laterally shifted sylvian groups of the middle cerebral arteries, and stretched bilateral internal cerebral veins. Judging from that angiographic findings and CT scan, we thought there would be cystic tumor in the IIIrd ventricle. However, we suspected the IIIrd ventricular tumor, we were not able to differentiated it from the enlarged IIIrd ventricle itself exactly. Because, it's density in CT scan was equaled with that the cerebrospinal fluid. According to above facts, we performed "Amipaque CT ventriculography through the ventricular catheter after V-P shunt. By "the Ampiqque CT ventriculography" we found exactly there was large cystic tumor in the IIIrd ventricle. Their manifestation and some differential diagnosis were discused.


Coronary surgery for unstable angina pectoris. Incidence and mortality of perioperative myocardial infarction. The incidence of perioperative myocardial infarction determined by electrocardiogram was examined in 123 consecutive patients having only coronary artery bypass grafting for unstable angina pectoris, at Yale-New Haven Hospital from January 1974 to June 1975. The incidence of myocardial infarction and its mortality were correlated with clinical, haemodynamic, anatomical, and operative factors. Myocardial infarction occurred in 18% of all patients (22/123); 15 inferior, 6 anterior, and 1 anterolateral wall. Three factors appeared to be related to the occurrence of myocardial infarction: left main coronary artery disease (LMCD), (47%, 7/15), increased left ventricular end-diastolic pressure (LVEDP), (27%, 14/52), and cardiopulmonary bypass time more than 60 minutes (24%, 21/88). The mortality of perioperative myocardial infarcation was 13.6% (3/22), while for patients without perioperative myocardial infarction the mortality was 2% (2/101). The overall operative mortality was 4% (5/123). The risk of perioperative myocardial infarction is significantly increased by left main coronary artery disease, increased left ventricular end-diastolic pressure, and cardiopulmonary bypass time more than 60 minutes, in patients undergoing coronary artery surgery for unstable angina pectoris. The mortality of perioperative myocardial infarction is high (13.6%) in patients with unstable angina.


Endocytosis of the antiprotease aprotinin by Landschütz ascites carcinoma cells and its effects in vitro and in vivo. Aprotinin was bound and endocytosed by Landschütz ascites carcinoma (LAC) cells in vitro. Addition of the antiprotease to cultures of these cells led to a dose-dependent growth-inhibitory and cytotoxic effect. In mice inoculated with LAC cells and treated with aprotinin there was a transient reduction in both the number and concentration of recovered ascites cells during the early phase of tumour growth. This was accompanied by a temporary increase in the proportion of peritoneal phagocytes (mononuclear phagocytes and polymorphonuclear leucocytes) relative to carcinoma cells. However, the number and concentration of ascites cells eventually achieved was comparable in saline and aprotinin-treated animals.


Formation of hyposorhodopsin in frog retina. Hypsorhodopsin was formed in frog retina by irradiation at liquid helium temperature and converted into bathorhodopsin above about 29K.


An electrogenic NA+/K+ pump in the choroid plexus. Intracellular electrical potential and potassium activity was measured by means of microelectrodes in the epithelial cells of choroid plexus from bullfrogs (Rana catesbeiana). Ouabain applied from the ventricular side caused an abrupt depolarisation of 10 mV but only a gradual loss of potassium from the cells. Readministration of potassium to the ventricular solution of plexuses which were previously depleted of potassium, caused a hyperpolarisation of about 4 mV. These two experiments are consistent with the notion of an electrogenic Na+/K+ pump situated at the ventricular membrane and which pumps potassium into the cell and sodium into the ventricle. The numerical values obtained suggest that 3 sodium ions are pumped for 2 potassium ions. The permeability coefficient for potassium exit from the cell is calculated to be 1.24 . 10(-5) cm-1 . s-1 expressed per cm2 of flat epithelium.


Organ cultures of human fetal hepatocytes in the study of extra-and intracellular alpha1-antitrypsin. The rate of synthesis of alpha 1-antitrypsin has been studied in organ cultures of fetal human liver. By de novo synthesis, alpha 1-antitrypsin of the same electrophoretic mobility and molecular size as plasma alpha 1-antitrypsin was produced. Synthetic rate was comparable to in vivo conditions and was suppressed by cycloheximide, colchicine and neuraminidase. By increasing alpha 1-antitrypsin levels in cultre medium, suppression of alpha 1-antitrypsin release from the intra-to the extracellular site was achieved, i.e., synthesis does not proceed autonomously. This suppression was preceded by a temporary enhancement of synthesis. Both effects were found to be independent of degree of sialylation of add-d alpha 1-antitrypsin. In contrast to alpha 1-antitrypsin released in tissue culture, the intracellular protein, as analyzed by crossed immunoelectrophoresis of Triton X-100 extracts from fetal liver, was found to occur partly as slowly moving peaks. Whether these peaks represent proforms or incompletely glycosylated precursors of export alpha 1-antitrypsin or complexes with proteases remains unsettled. A variety of other plasma proteins are released in organ cultures making the system suitable for study of factors regulating plasma protein synthesis.


Picosecond dynamics of primary electron-transfer processes in bacterial photosynthesis. The primary electron transfer processes in Rhodopseudomonas sphaeroides R-26 were studied as a function of temperature by means of picosecond spectroscopy. The first chemical step of the bacterial photosynthesis involves an electron transfer from the excited state of a bacteriochlorophyll a dimer, (BChl)2, to a bacteriopheophytin (BPh) to form the radical ion pair (BChl)2+. BPh-.. The upper limit for the formation time of this ion-pair was found to be 10 ps, at temperatures in the range 300-4.2 degree K. Similarly, the second chemical step, involving electron transfer from BPh-. to an ubiquinone-iron complex (QFe), was found to have a lifetime of approximately 150 ps, also independent of temperature in the same range. We interpret the absence of temperature dependence as indicating that process 2 proceeds via a tunneling mechanism. Utilizing our results in conjunction with electron tunneling theories, we calculate the distance between BPh-. and Q(Fe) to be 9--13 A. Our results also imply a closer proximity between (BChl)2 and BPh.


Biochemical and behavioral effects of serotonin neurotoxins on the nigrostriatal dopamine system: comparison of injection sites. Unilateral injections of the serotonin neurotoxin, 5,7-dihydroxytryptamine (DHT), at various points along the 5-HT pathway to the forebrain produce a turning syndrome associated with alterations of dopamine synthesis in the ipsilateral striatum. Unilateral injections of DHT into the SN produced an ipsilateral increase in striatal dopamine (DA) turnover and contralateral rotation in response to amphetamine or apomorphine. Injection of DHT into the MFB produced an ipsilateral decrease in striatal DA turnover and tyrosine hydroxylase (TOH) activity, and ipsilateral rotation in response to amphetamine or apomorphine. After the injection of DHT into the SN or MFB, there was a significant correlation between the rates of drug-induced rotation, the decrease in cortical 5-HT turnover, and the change in striatal DA turnover, suggesting that the unilateral change in DA turnover (and, presumably, the increased stimulation of DA receptors) is causally linked to turning. Injection of DHT into the zones of the striatum and GP richest in 5-HT terminals produced the same responses as the MFB-lesioned rats: ipsilateral rotation and a decrease in striatal TOH activity. Injection of DHT into the area of the striatum richest in DA terminals failed to produce rotation or a significant change in TOH activity. We suggest that 5-HT neurons from the raphe nuclei exert a tonic inhibition on the nigrostriatal pathway at the level of the SN through direct synapses on DA neurons, whereas their neostriatal terminals have an indirect effect on DA terminals, perhaps via interaction with cholinergic and GABA-ergic neurons.


Behavioral and prolactin responses to 5-hydroxytryptophan in rats treated during development with 5,7-dihydroxytryptamine. The serotonin precursor, 5-hydroxytryptophan (5-HTP), can induce a behavioral syndrome characterized by rigidity, splayed feet, tremor, head weaving, salivation and forepaw treading. This response to 5-HTP was markedly potentiated in adult rats treated intracisternally with 5,7-dihydroxytryptamine (5,7-DHT) during development. Prevention of the 5,7-DHT-induced reduction of brain norepinephrine with pargyline or desipramine did not diminish the potentiation of 5-HTP, suggesting that noradrenergic fibers are not contributing to the altered 5-HTP response. It was also found that treatments with 5,7-DHT potentiated the release of prolactin and the disruption of responding in a fixed-ratio operant task induced by 5-HTP. Other experiments indicated that 5,7-DHT treatments potentiated 5-HTP without affecting the action of L-dihydroxyphenylalanine. In addition, administration of the decarboxylase inhibitor, R0-4-4602, at a dose that inhibits enzyme activity in brain, blocked the 5-HTP-induced behavioral syndrome in 5,7-DHT-treated rats, indicating that 5-HTP must be converted to serotonin for 5-HTP to alter behavior. Thus, the present studies indicate that destruction of serotonergic fibers during development can produce permanent changes in central serotonergic mechanisms.


Failure of immunogenic tumors to elicit cytolytic T cells in syngeneic hosts. Immunogenic, methylcholanthrene-induced sarcomas failed to elicit the production of rapidly cytolytic T lymphocytes in syngeneic mice, although they did elicit the production of more slowly cytotoxic cells. They were, however, susceptible to attack by cytolytic T cells from allo-immune mice and, if infected with ectromelia virus, to attack by similar cells from virus-immune, H-2 compatible mice. It is suggested that the failure to elicit cytolytic T cell production may be due to the lack of an appropriate association between tumour-specific antigens and elements of the major histocompatibility complex.


Treatment of mycosis fungoides lymphoma: effectiveness of infusions of methotrexate followed by oral citrovorum factor. Eleven patients with stage II or III mycosis fungoides lymphoma were treated with a regimen consisting of iv infusions of methotrexate (MTX) (60-240 mg/m2) administered sequentially and oral citrovorum factor. All 11 patients experienced a good to excellent response. Complete remissions were induced in seven of the 11 patients. In most cases remissions were sustained with weekly administration of low-dose (25--50 mg) MTX. Adverse drug reactions, such as leukopenia, anemia, and mucositis, were minimal in degree. Some unique adverse reactions included skin ulcerations (three patients), a leukocytoclastic angiitis (one patient), and painful hands and feet during MTX infusions (two patients). Our experience with this regimen has led us to conclude that it is safe and very effective in the treatment of stages II and III of mycosis fungoides.


Effect of myleran on murine hemopoiesis. I. Granulocytic cell line specificity of action on progenitor cells. Time- and dose-dependent patterns of depletion and regeneration of hemopoietic progenitor cells in mouse femora and spleens following treatment with the antileukemic agent Myleran (Busulphan, MY) were studied using the murine spleen colony system and the agar gel in vitro colony system. MY was found to depress granulopoiesis selectively, as manifested by the development of marked prolonged neutropenia, hypoplasia of the bone marrow and (to a lesser degree) of the spleen, reduction of the incidence of multipotential hemopoietic progenitor cells (CFU-S) and of granulocytic progenitor cells (CFU-C) in both femora and spleens, and impairment of the capacity of CFU-S from either tissue to generate granulocytic colonies in the spleens of irradiated hosts. The severity and duration was greatest at high dose levels of MY (800 microgram). The action of MY on CFU-S was more pronounced than that on CFU-C, suggesting that MY is a cycle-independent agent. Repopulation of the CFU-C pool preceded that of the CFU-S pool. Development of neutropenia and maximal marrow hypoplasia followed the onset of depression of CFU-S and CFU-C incidence, while recovery of normal nucleated cellularity in the blood, femur and spleen preceded repopulation of the CFU-S and CFU-C pools. MY treatment resulted in transitory stimulation of colony stimulating factor (CSF) generation by the femur but had no effect on serum CSF levels. The peak of femoral CSF generation coincided with the nadir of CFU-C depression. These findings indicated that the prolonged neutropenia following MY treatment was secondary to depletion of the progenitor cell pools, that during recovery granulopoietic repopulation took precedence over self-maintenance of the hemopoietic progenitor cell pools, and that increased generation of CSF may play a role in the early phase of granulopoietic recovery.


Stimulating factors and cell recruitment in murine bone marrow stem cells and EMT6 tumours. The role of a stimulating factor in cell recruitment and the kinetics of its secretion were investigated by in vivo and in vitro techniques. The association of these two methods made it possible to demonstrate that a non-cycling population liberates a factor which in turn stimulates quiescent bone marrow stem cells into DNA synthesis. Moreover, it seems that undamaged cells are capable of secreting this factor. A stimulating factor responsible for cell recruitment was also demonstrated in an experimental EMT6 tumour and the kinetics of its secretion reported.


Model of skin vascularization in Rana esculenta L.:  scanning electron microscopy of microcorrosion casts. Microcorrosion casts of blood vessels in the skin of Rana esculenta L. were examined by means of scanning electron microscopy with particular reference to the subepidermal network of respiratory capillaries. Due to the fact that arteries and veins lie in the deeper layers of the stratum spongiosum of the corium, the respiratory vessels form a morphologically homogeneous network. Functionally, however, this network is subdivided into small areas with a centripetal direction of blood flow. The deep capillary net, situated at the base of the stratum compactum of the corium, is not so dense as the respiratory network and does not directly communicate with it. Alveolar glands of the skin have no effect on the distribution of capillaries in the two networks.


Stereological model system for free cells and base-line data for human peripheral blood-derived small T-lymphocytes. T-lymphocytes derived from human peripheral blood and passed through a nylon-wool column, were employed to develop and test a new stereological model system for free spherical cells, allowing a quantitative characterization of the cell and its components at the ultrastructural level. Electron micrographs were recorded in a hierarchical manner at three different levels of magnification and subjected to point counting procedures. The resulting parameters were expressed in relation to various reference compartments, both absolute and relative. Results indicated that the average volume of a small, non-activated T-lymphocyte was 103.8 micron3, the nuclear volume 47.5 micron3 and the cytoplasmic volume 55.9 micron3. On the average, the cytoplasm contained 30 mitochondria, 0.7 micron3 RER-cisternae, 0.2 micron3 cisternae and vesicles of the Golgi apparatus and about 231,000 free ribosomes (most of them single). The ratio of eu- to heterochromatin volume was 0.5. The design and application of the stereological model system are discussed with regard to dynamic studies of a variety of free cells, such as macrophages, neutrophilic granulocytes and various lymphocytes.


Healthy family functioning: a cross-cultural appraisal. It is increasingly recognized that rapid cultural, social, economic, and technological changes are imposing increasing stress on family structures, traditional values, and the ability to adapt to new environments in different societies. For the purposes of this paper, "healthy family functioning" is defined in terms of a family unit (however it is conceived in any given culture) effectively coping with cultural, environmental, psychosocial, and socioeconomic stresses throughout the family life cycle. While a review of international literature in the behavioural and biomedical sciences yields little data on comparative studies, there is growing awareness of the need for cooperative international research on family coping mechanisms and determinants of self-reliant communal coping behaviour, as well as more efficient utilization of already available knowledge. After consideration of methodological pitfalls of assessment procedures, there is a presentation of an evolving theory of healthy family functioning with the suggestion that studies of young married couples constitute a particularly promising vehicle for developing needed cooperative cross-cultural research.


Fertility regulation in the male.

Fertility regulation in the male. The current state of research into new methods of male contraception is reviewed, with special emphasis on the efforts of the WHO Special Programme of Research, Development and Research Training in Human Reproduction. The article concentrates mainly on the development of orally administered or injectable substances capable of either (a) interfering with the hormonal control of testicular function, (b) disrupting spermatogenesis by direct influence on testis function, or (c) interfering with the fertilizing ability of the sperm and their transport. It is concluded that, despite the numerous areas of research currently being pursued, the availability of a new male contraceptive remains several years away.


Epidemiology and control of schistosomiasis: present situation and priorities for further research. Scientific Working Group on Schistosomiasis. The article highlights specific aspects of the epidemiology of schistosomiasis where insufficient data are available on which to base appropriate control strategies. Emphasis is placed on the part that immunological techniques might play in improving the baseline epidemiological data. A study of acquired resistance to the disease is also important in relation to epidemiology and control. The clinical manifestations of the disease vary in different areas and further study of the relation between the clinical and pathological manifestations are therefore required. In relation to the intermediate host, the main priority for research concerns the definition of the location and time-patterns of transmission foci within any particular area: variations in transmission are of particular importance in relation to man-made water resources. Although chemotherapy will play an increasing role in control, its importance will depend on local conditions: coordinated and standardized trials are required of chemotherapeutic agents in different regions and in various defined groups of subjects. The effects of chemotherapy on immunity to reinfection and on immunopathology also require study. With all types of snail control-chemical, ecological, and biological-cost-effectiveness aspects are important. With chemicals, it is important to bear in mind other possible effects on the environment. In the field of water supplies and sanitation, several aspects are important in relation to schistosomiasis transmission and community involvement should be encouraged.


Water-contact patterns in relation to Schistosoma haematobium infection. Water-contact observations were carried out on a population exposed to Schistosoma haematobium in a village situated on a man-made lake, Lake Volta, Ghana.The observations were made over a period of 12 months prior to the introduction of control measures. A multiple regression analysis was performed on the results of observations on 132 individuals, with egg output as the dependent variable and various types of water-contact activity, as well as age and sex, as independent variables. In the analysis, specific activities, notably water-contact for domestic purposes and activities associated with fishermen's canoes, were found to be significantly related to schistosomiasis. Age was less important than degree of exposure as a contributory factor to variations in infection rates: the reduced intensity of infection of S. haematobium in the older age groups could be mainly due to a lower level of exposure to the cercarial population.


A cold box for the transport and storage of vaccines. A cold box capable of maintaining a temperature below +4 degrees C for 1 week was constructed and tested in the laboratory and under field conditions. Cooling is produced by commercial cold packs precooled in a deep-freeze or the freezing compartment of a refrigerator. The box can take approximately 3000 doses of vaccine and is simple, cheap and strong. It is primarily intended for storage of vaccines during field trips by vaccination teams, as an alternative to the refrigerator in regional and peripheral stores in the case of an electrical power failure, and for the delivery of vaccines from regional store to the district.


The Styx Field Trial: effect of treatment of the definitive host for tapeworms on larval forms in the intermediate host. A 13-year assessment has been made of the effectiveness of a monthly drug treatment programme for the control of tapeworms in dogs in order to prevent hydatidosis (Echinococcus granulosus) and cysticercosis (Taenia hydatigena and T. ovis) in sheep. The age-specific prevalence of T. hydatigena in lambs was used as the principal indicator. The trial was carried out in the Styx Valley of the Maniototo Plain in the South Island of New Zealand.Over an 8-year period dogs were treated monthly with bunamidine hydrochloride at about 25 mg/kg with little effect on the prevalence of T. hydatigena in lambs. The addition of niclosamide at 50 mg/kg for 1 year also had little effect. Eggs appeared to survive from one season to the next. Those shed prior to the lamb-rearing season gave rise to endemic-type patterns; whereas patent infections occurring during this period rapidly gave rise to an epidemic-type pattern or a "cysticercosis storm". In this 9-year period there were 16 "cysticercosis storms" and all susceptible lambs were infected. These storms did not necessarily give rise to a similar prevalence on neighbouring farms, but may have contributed to the overall infective pattern. A similar situation occurred in the first year that nitroscanate at 100 mg/kg was introduced. During this 10-year period, arecoline surveillance of the dog population was undertaken in the remainder of the county and many dogs were found to harbour tapeworms. Both resident and introduced dogs may have contributed to the infective patterns in the Styx Valley.Treatment with nitroscanate was continued monthly in the Styx Valley and niclosamide was used in the remainder of the County for a further 3 years. There was a marked reduction in the age-specific prevalence and lambs on many farms were free from T. hydatigena at slaughter. However, one "breakdown" occurred and this was almost certainly autochthonous.Comparisons with an earlier period when arecoline surveillance was used in the Styx Valley, indicate that the present evidence favours a drug-orientated treatment programme of the definitive host for the control of cysticercosis. However, "breakdowns" caused by either autochthonous or itinerant sources have profound effects, since they involve all susceptible age-cohorts including those that have never been infected and those that have lost the immunity induced by an earlier infection.


Evaluation of fenitrothion for the control of malaria. Fenitrothion was evaluated for residual spraying in antimalaria programmes in a large-scale field trial near Kisumu, Kenya from 1972 to 1976. The insecticide was applied in a hyper/holoendemic malarious area of 200 km(2) inhabited by about 50 000 people. All houses and animal shelters were sprayed at a target dosage rate of 2 g/m(2) at 3-month intervals for a total of 8 consecutive spray rounds in 2 years. The malaria vectors Anopheles gambiae species A and B and A. funestus were reduced to negligible densities indoors and outdoors immediately after initiation of spraying and for 10 months after the last spray round. However, A. gambiae reappeared during the main wet season at densities high enough to reestablish low-level transmission for short periods. Spraying produced a marked and rapid decrease in both the incidence and prevalence of malaria. The daily probability of acquiring malaria infection was reduced from 0.009 before spraying to 0.0003 under spray protection, a reduction of 96%. Data collected on a longitudinal basis indicated that sustained spray protection would reduce malaria prevalence to an asymptotic limit of 6.9% under the assumption that the inoculation and recovery rates remain stable. However, to attain malaria eradication in this type of epidemiological situation, complementary measures such as mass drug administration appear to be necessary.


Genetic sex separation in Anopheles arabiensis and the production of sterile hybrids. The gene for dieldrin resistance has been artificially male-linked so that females can be selectively killed with dieldrin. By intercrossing different sibling species of the Anopheles gambiae complex, batches consisting of sterile males only can be reared. This seems to have potential for use in genetic control operations.


Progress towards the colonization of Cnephia mutata (Diptera: Simuliidae). Cnephia mutata was successfully induced to complete two entire generations in the laboratory. Owing to its triploid condition, this simuliid is parthenogenetic and mature eggs may be dissected from the ovaries, thus eliminating both mating and oviposition. C. mutata in Newfoundland is also autogenous, making blood-feeding unnecessary. Progress towards colonization of this species is reviewed.


Occupation, education, and income as socioeconomic indicators in relation to cardiovascular risk factors in the urban African. A yardstick is needed for measuring the medical consequences of socioeconomic change in developing countries. Education, income, and a newly developed occupation index were studied in urban African males in relation to six coronary artery disease risk factors. Occupation was the status indicator best known to a man's family, correlated best with the risk factors, and was not age dependent.


Proposals for the nomenclature of salivarian trypanosomes and for the maintenance of reference collections. Studies on the characterization of salivarian trypanosomes are at present developing rapidly and difficulties in communication tend to arise because of different procedures in the different laboratories concerned. Terms can be divided into two classes, those that are purely operational and simply describe the laboratory history of the organism, and those that imply characterization. Of the Linnaean taxa, the section Salivaria and the four subgenera thereof, Duttonella, Nannomonas, Pycnomonas, and Trypanozoon, are useful at the present time but lower taxa are often unsatisfactorily defined. Characters such as the clinical course of infection, which have been used for subspeciation, are being found to correlate with such characters as isoenzyme patterns, antigenic make-up and DNA constitution.Serial passage of organisms has serious disadvantages and so reference collections are primarily of stabilates-cryopreserved suspensions of living organisms. Methods for the preparation of antigens, antisera, and isoenzymes are briefly noted.Conventions for the documentation of reference collections are proposed, in particular that the designation of materials should consist of two components, one signifying the primary isolation and the other the particular derived material used. The requirements for rapid information retrieval and global cataloguing of materials are considered.


Acute respiratory infections: a review.

Acute respiratory infections: a review. Acute respiratory infections (ARI) constitute one of the principal causes of morbidity and mortality in many countries. Data from 88 countries in five continents, with a total population of nearly 1200 million, showed that deaths due to ARI in 1972 amounted to 666 000. Pneumonia, both viral and bacterial, accounted for 75.5% of the total deaths from ARI. Mortality from ARI represents 6.3% of deaths from all causes. Considerable differences in mortality rates exist both between and within continents. Mortality from ARI is highest in infants and old people. The data suggest that in some areas of the world mortality due to ARI is extremely high.


Kinetic measurement of alpha-amylase with a centrifugal analyzer. We compared results of an enzymic assay for alpha-amylase (EC 3.2 1.1), adapted to a centrifugal analyzer (GEMSAEC), with results by the manual dyed-starch (Phadebas) amylase assay. We assessed linearity and precision, and the stability of the reagent. The kinetic procedure is rapid, precise, requires only 25 microliter of serum, and thus is evidently suited for both pediatric and emergency use.


Decreased suppressor cell activity in inflammatory bowel disease. Studies were performed on eleven patients with inflammatory bowel disease to determine if there was an alteration in concanavalin A (Con A) induced suppressor cell activity. Similar investigations were also performed on twenty-one control subjects and five patients with other inflammatory conditions. Supressor cells were generated by pre-incubation of peripheral blood mononuclear cells with a mitogenic concentration of Con A, followed by treatment with mitomycin C and alpha-methyl mannoside. Under these conditions, cells obtained from normal individuals are then capable of suppressing the Con A-stimulated blast transformation responses of fresh allogeneic lymphocytes in new cultures. We found that in twenty out of twenty-one control subjects, and all five patients with other inflammatory disorders, Con A-stimulated suppressor cell activity was demonstrable. Four patients with inflammatory bowel disease, whose disease was mildly active or was in clinical remission, had elicitable suppressor cell activity which fell within the normal range. In contrast, suppressor cell activity was markedly diminished or absent in seven patients with severe and active inflammatory bowel disease. These studies suggest that an alternation in Con A-stimulated suppressor cells exists in patients with active inflammatory bowel disease, which may contribute, in part, to the persistent inflammation in the gastrointestinal tract.


In vitro studies of suppressor cell function in human peripheral blood mononuclear cells. Peripheral blood mononuclear cells (PBMC) from normal donors, pre-cultured at 37 degrees C for 24 hr before the addition of mitogen, demonstrated an enhanced proliferative response. This may be due to the loss of a subpopulation of suppressor cells during the incubation period. Still further enhancement was observed when pre-culturing was prolonged for 48 hr, while cells pre-incubated at 4 degrees C showed no increased responsiveness. Concanavalin A (Con A) pre-activated PBMC supressed the mitogen response of responder cells. More marked suppression was observed when the concentration of Con A used to induce the suppressor cells was increased. It was not possible to activate suppressor function in cells which had been kept in vitro for longer than 48 hr. These findings support the concept of the existence and function of suppressor cells, and that the suppressive influence is short-lived in vitro culture.


Is the adherent, non-specific 'suppressor' cell from rodent spleens an in vitro artefact? Mitomycin C-treated cells from the spleens of mice pre-treated with BCG, Corynebacterium parvum, cyclophosphamide or methylcellulose will inhibit the mitogen responses of normal cells in vitro, but extended dose-response studies have shown that such cell populations will also enhance the response if added in very small numbers. The number of cells giving peak enhancement is proportional to the percentage of the spleen cells which are adherent at 72 hr. Such late-adhering cells are not removed by conventional adherence column techniques. The concept of the adherent suppressor T cell is discussed in the light of these findings.


Monocyte-dependent stimulation of human T cells by zinc. Subpopulations of human peripheral blood leucocytes were isolated by nylon filtration or E-rosette separation and tested for functional activity. As shown previously, zinc ions induce DNA synthesis in unfractionated lymphocyte cultures. E-rosette-forming cells (E-RFC), obtained either by nylon wool filtration or E-rosette separation, responded well to PHA but showed only low levels of proliferative reactivity to zinc and Con A. These dminished responses could be completely restored by the addition of small numbers of autologous, mitomycin-treated monocytes; further experiments suggested that a monocyte-derived soluble factor can substitute for monocytes in this function. B lymphocyte-enriched cell populations, containing less than 1% E-RFC, did not respond to zinc and showed only marginal reactivity to PHA and Con A.


In vitro modulation of lymphocyte responses to phytohaemagglutinin by plasma in mother and baby at the time of birth. Increased lymphocyte responses in babies of mothers with lepromatous leprosy. Peripheral blood lymphocytes from nineteen healthy mothers, mothers with borderline tuberculoid leprosy and fourteen mothers with borderline or polar lepromatous leprosy, and their newborn babies, were stimulated in vitro with phytohaemagglutinin (PHA). The responses in medium supplemented by serum from a pool of healthy non-pregnant individuals were compared with responses in medium supplemented by plasma from the mothers or from their babies, to assay for the presence of non-specific effects on T-cell responses. It was found that plasma from the mothers at the time of labour profoundly suppressed their own lymphocyte responses to PHA. However, the lymphocyte responses of healthy mothers were not significantly suppressed when cultivated in the presence of plasma from the babies, indicating that the suppressive factor(s) of normal pregnancy did not pass the placental barrier. Plasma from mothers with leprosy had a greater inhibitory effect on their babies' lymphocytes than plasma from healthy mothers. This raises the possibility that plasma from leprosy patients contains suppressive factors other than those associated with pregnancy. Babies of lepromatous leprosy mothers, who might have been exposed to mycobacterial antigens in utero, had higher PHA responses than the other babies, possibly due to a compensatory reaction to early stresses in the immune system.


Longitudinal studies showing alterations in the levels and functional response of T and B lymphocytes in human pregnancy. Altered blood levels of T and B lymphocytes were found in the first half of human pregnancy. A total of twenty-two women were tested, using direct or indirect rosetting assays or the fluorescence-activated cell sorter, to determine the levels of peripheral blood T and B cells. In all cases, an inversion of T- and B-cell levels was observed, i.e. T-cell levels were decreased and B-cell levels (as measured by the presence of surface immunoglobulin or the presence of B-cell surface antigens) were increased. This inversion was exhibited as early as 1 week post-implantation. Lymphocytes from two fo the women were also examined for stimulation with phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) at intervals during gestation, and the amount of [3H]thymidine uptake was compared to that of two non-pregnant women tested at each interval. The values obtained for the pregnant women with PHA were markedly lower, and with pokeweed mitogen slightly lower, than those of non-pregnant controls. However, the PHA and PWM values in the pregnant women returned to levels similar to those of the nonpregnant women shortly after the T- and B-cell levels returned to normal. Thus the decrease in the response of the lymphocytes to mitogens during early pregnancy appears to parallel the numerical deficiency of T cells.


[Factors contributing to the impairment of cellular immunity in cancer patients (author's transl)]. Factors contributing to the impairment of cell-mediated immunity in cancer patients were studied. Normal plasma enhanced the PHA-induced transformation of cancer lymphocytes. Cancer plasma suppressed the transformation of normal lymphocytes. The plasma factor(s), which might play an important role in the impairment of cell-mediated immunity in cancer, was further characterized to be heat-labile, being completely destroyed at 56 degrees C for 30 minutes. It was present on the surface of T lymphocytes, and was partially removable by digestion with 0.05% Bacto-trypsin. Moreover, the percentage of T cells in the peripheral blood of cancer patients was lower than that of normal as determined by the anti-human thymocyte serum cytotoxicity test and the spontaneous rosette forming test.


[Baby hamster kidney cells as antigen for demonstration of antinuclear antibodies (author's transl)]. Baby hamster kidney cells fixed in acetone on glass slides were used as antigen for demonstration of antinuclear antibodies. Where certain storage conditions were observed (drying agent, 4 degrees C) they have kept for 12 months up to now. As regards specificity, sensitivity, reproducibility, and differentiation of fluorescent types the baby hamster kidney cell test appears superior to other immunofluorescence methods used (chicken erythrocytes, rat liver sections, and crithidiae). These results were obtained in 73 sera from patients with disseminated lupus erythematodes, drug-induced lupus erythematodes, discoid erythematodes, allergic vasculitis, progressive scleroderma, dermatomyositis, and 36 control sera.


[Gingival bleeding test with a new tonometer and testing of a chlorhexidine containing dentifrice]. A novel gingival tonometer is introduced with which definable pressures from 8.2-196.7 p/mm2 on the gum can be exerted. Bleeding from the gum can be produced by definable pressure, relating the inflammatory condition to the pressure insult and so achieving objective measurements. In 53 cases of periodontitis marginalis the results of treatment with a mouthwash containing chlorhexidine was tested. The gingivitis was so far improved by one week's treatment with the rinsing combination that in 1287 periodontitis cases the pressure had to be doubled before bleeding was produced.


Grafting of triggering sites onto lymphocytes: requirement of multivalency in the stimulation of dinitrophenyl-modified thymocytes by anti-dinitrophenyl antibody. N4-Dinitrophenyl-L-2,4,-diaminobutyric acid hydrazide was coupled to aldehyde groups generated by periodate oxidation of sialyl residues on thymocytes. Anti-2,4-dinitrophenyl(Dnp)antibody was found to stimulate mature, hydrocortisone-resistant thymocytes, while it had no mitogenic effect on the immature thymocytes. In order to study the involvement of different regions of the antibody molecule in the triggering process of stimulation, the mitogenicity of various antibody fragments was also assessed. The divalent F(ab')2 was found to be a superior mitogen compared to the intact antibody when added to Dnp-conjugated thymocytes. The monovalent Fab' and Fab fragments have no mitogenic activity indicating that cross-linkage may be a prerequisite for stimulation.


T cell-dependent suppression of antibody production. I. Characteristics of suppressor T cells following tolerance induction. Specific immunological tolerance was induced in adult CBA mice by a single injection of deaggregated human IgG (dHGG). Spleen cells taken 7 to 42 days later, produced consistent suppression of a DNP-HGG collaborative antibody response on adoptive transfer into heavily irradiated recipients. Noncentrifuged F(ab')2 fragments of HGG were as effective as dHGG in the production of suppressor cells. Suppression was antigen-specific since HGG-tolerant cells failed to abrogate either a DNP-keyhole limpet hemocyanin collaborative response or antibody production to the noncross-reactive antigen, horse erythrocytes. Pretreatment of the tolerant cell population with anti-Thy-1 serum and complement reversed the suppressive effect. However, purified tolerant T cells obtained by passage through nylon wool or anti-Ig columns were less effective than the original spleen cells in mediating suppression. Analysis of the cell types appearing in the column effluents indicated that the reduction in suppressive activity is best explained by retention of T cells rather than macrophages. Different T cell populations, however, were retained on the two types of columns. In the case of anti-Ig columns, these consisted of Ly-2,3+, Ia+ effector cells, whereas nylon wool columns caused depletion of Ly-1,2,3+ cells which are known to act as amplifiers of suppression. Suppression could not be explained in terms of delay in differentiation of antibody-forming cell precursors since the effect persisted for up to 15 days after transfer of tolerant cells. The demonstration of a reduction in serum anti-DNP and anti-HGG antibodies excluded the possibility of antibody production in sites other than the spleen. A role for anti-carrier antibody-antigen complexes in mediating the effector phase of suppression was rendered unlikely by the finding that the suppressive effect of tolerant cells persisted in the absence of detectable anti-HGG antibody production. Effector T cells mediating suppression in this system were shown to bear the phenotype Ia+, Ly-2,3+ as judged by the effect of pretreatment with appropriate antisera and complement. They were spleen-seeking, but were not detected in the thymus or recirculating lymphocyte pool. Adult thymectomy failed to cause a significant reduction in suppressive activity by tolerant spleen cells indicating that at least a major component of the immediate precursors is not of recent thymic origin.


Possible occurrence and meaning of lymphocytes bearing autoanti-idiotypic receptors during the immune response. During an immune response, the increase in binding affinity of antibodies is followed by a fall. Lymphocytes bearing autoanti-idiotypic receptors were detected during a normal immune response. The kinetics of appearance and disappearance of such lymphocytes led us to propose a network model to explain the changes occurring in antibody properties during an immune response.