Macrosomia. A proposed indication for primary cesarean section. Fetal macrosomia (birthweight equal to or in excess of 4500 g) in a study of 110 affected infants was associated with excessive maternal weight, prolonged gestation, white race, multiparity, maternal diabetes, male fetus, and a previous macrosomic infant. The two most common obstetric complications associated with fetal macrosomia were postpartum hemorrhage and shoulder dystocia. One-minute Apgar score was less than 7 in 10.9% of the macrosomic infants, in contrast to 6.3% for the smaller infants studied as controls. The low fetal mortality rate (1.8%) was attributed to a 22.5% cesarean rate for the macrosomia group. Even more frequent use of abdominal delivery might further reduce obstetric and neonatal complications for macrosomic infants.


Intraarterial pelvic infusion chemotherapy in advanced gynecologic cancer. Fourteen patients with advanced localized gynecologic cancer were treated with 44 courses of intraarterial pelvic infusion chemotherapy. All patients received methotrexate with folinic acid rescue; 9 patients also received vincristine. Tumor regression was observed in 3 of 14 patients (21.4%). In 5 patients there were major complications related to 28 intraarterial catheter placements. Two patients developed leukopenia following chemotherapy. The value of intraarterial infusion chemotherapy in gynecologic cancer is limited. Its use in gynecologic oncology is discussed.


[Radioautographic analysis of from peripheral blood and a focus of inflammation in amphibia]. In the peripheral blood of intact amphibians the cells of big lymphocyte type (light-nuclear forms) only are capable to incorporate 3H-thymidine. The implantation of foreign bodies in the subcutaneous lymphatic sac of R. temporaria induced the appearance in the circulating blood of one more cell form (dark-nuclear cells) capable of DNA synthesis. The autoradiographic analysis of interrelations between these forms allows to consider them as stages of one histogenesis.


[Differentiation of hematopoietic cells in explants of embryonal organs of Rana temporaria L]. The potencies of isolated embryonic hemopoietic organs (pronephros and liver) of Rana temporaria L. to the formation of the foci of hemopoiesis were studied. The pronephros and liver rudiments were explanted at the early developmental stages (late neurula and early tail bud) and cultivated in vivo in the diffusion chambers. The blast hemopoietic elements and differentiated blood cells are found in the explants within 7 to 10 days of cultivation. A suggestion is put forward that the differentiation of hemopoietic cells in the embryonic hemopoietic organs proceeds from the local cells-precursors.


[Eosinophilic granuloma of the conjunctiva]. The histology of a case of dermal and conjunctival eosinophilic granuloma in a 74-year-old female patient is described. The aetiology could not be established until now. The differential diagnosis of atypical histiocytosis X, eosinophilic leukaemoid and eosinophilia persistens is discussed.


[Recurrent dystrophic erosion of the corneal epithelium]. In the majority of cases there exists, at the beginning of the recurrent dystrophic erosion of the corneal epithelium, a slight superficial trauma. There are, neverthless, also spontaneous forms, which are more often bilateral, hereditary forms and secondary forms with more generalized corneal dystrophies. (2) Between the trauma and the appearance of the recurrent  erosion there is always a latency period of variable duration. (3) Women are more often affected than men. The condition usually is observed between 25 and 40 years of age. (4) The epithelial erosions reoccur at irregular intervals nearly always in the morning when the eyes are opened. They are always localized below the pupillary area and not necessarily at the site of the trauma. (5) Between two recurrences, there persists a latent epithelial dystrophy, which is characterized by subjective symptoms (pricking pain in the morning at the opening of the eyes) and by objective signs (grey epithelial spots or epithelial microbullae below the pupillary area near the vertical meridian). (6) At the light and electron microscope one sees alterations of the basal epithelial cells, intra epithelial cysts, ruptures of the basement membrane and disappearance of the hemidesmosomes. (7) The disorder is a true epithelial dystrophy, the traumatism being only an occasional cause. (8) The treatment is discussed.


Autosomal recessive incomplete achromatopsia with protan luminosity function. A unique form of dichromatic color vision is described in a family with incomplete achromatopsia. In 1966, incomplete achromatopsia was diagnosed in 4 of 14 children of a consanguineous marriage. The 4 affected had best visual acuities of 6/60 or 6/180, pendular nystagmus, and aversion to bright lights. The ERG showed minimal photopic responses. No abnormality of rod function was present. There was a severe color vision defect. In 1976, one of the patients returned for further color testing. Color tests included measurement of the luminous efficiency function using heterochromatic flicker photometry and colorimetric evaluation. The luminous efficiency function resembled that of the protanope. From the colorimetric measurements, we conclude that the patient has a unique form of dichromatic color vision mediated by two visual photopigments: the normal MWS cone photopigment and a photopigment with the spectral characteristics of rhodopsin.


Middle ear ciliary defect in Kartagener's syndrome. Patients with Kartagener's syndrome have shown electron photomicrographic abnormalities of nasal or bronchial cilia in addition to functional defects of mucociliary transport (immotile cilia syndrome). This report describes a boy with Kartagener's syndrome and chronic otitis media who demonstrates electron photomicrographic abnormalities of middle ear cilia, confirming the important role of cilia in providing protection against infection of the middle ear.


Congenital vesicular eruption caused by Haemophilus influenzae type b. We report a case of perinatal infection that we believe is the first documented report of a congenital vesicular eruption due to Haemophilus influenzae type b and the second report of puerperal sepsis with this organism. A vesicular eruption was noted at birth on an infant delivered at 37 weeks following 34 hours' premature rupture of membranes. Gram-negative rods were seen on Gram stain of vesicular fluid, and H. influenzae type b grew on cultures of vesicular fluid. The mother sustained postpartum septicemia with the same organism. Amnionitis and funistis were demonstrated histologically. Results of all viral studies were negative. Infant and mother did well with antibiotic therapy.


Tension responses of frog sartorius muscle to quick ramp-shaped shortenings and some effects of metabolic inhibition. The dynamic properties of the contractile mechanism of skeletal muscle were investigated in electrically stimulated sartorius muscle of the frog at 0 degrees C by analysis of the force responses to quick changes in length. 1. The tension responses to ramp-shaped shortenings at different rates of shortening have been recorded. The tension course during the ramp is described in terms of a damped elastic element. In addition a maximum value for an additional series elastic element is estimated. 2. The tension reponses to pulse-shaped shortenings have been recorded. At least 15 ms after the pulse a minimum in tension is found, which depends on amplitude and duration of the pulse. This effect is optimal at a pulse duration of about 6 ms. It is concluded that within 15 ms after the pulse detachment of crossbridges occurs. 3. Muscles were incubated with the metabolic inhibitors IAA and FAA or IAA and FDNB. After repeated stimulation, but before the muscle passes into the rigor state, the fast recovery and the plateau in the responses to quick shortenings are either diminished or abolished, depending on the amplitude of the shortening. This can be explained by assuming that in the unpoisened muscle, ATP enables the crossbridges to exert temporarily a larger force.


A large scale preparation of peanut agglutinin on a new affinity matrix. A simple and rapid method for the purification of Peanut Agglutinin by affinity chromatography on cross-linked arabinogalactan is described. Cross-linked arabinogalactan shows a high capacity for PNA. The lectin has been obtained to electrophoretic purity and has a high hemagglutinating specific activity.


The isolation and characterization of plasma membranes from calf thymocytes. A simple method is described for the isolation and characterization of plasma membranes from calf thymocytes. The procedure involves extraction of thymocytes in a hypotonic medium containing borate and EDTA. Membrane ghosts, obtained by centrifugation of the cell lysate, are purified by passage through a column containing glass beads. The purity of plasma membranes was checked by chemical analysis, by assay of marker enzymes and also by electron microscopy. Polyacrylamide gel electrophoresis of the calf thymocyte plasma membrane produced a number of protein bands as well as a major band which stained for carbohydrate. The method is rapid and could be applied to isolate plasma membranes from nucleated cells of various types in large quantities.


Role of peripheral mechanisms in the behavioral effects of 5-hydroxytryptophan. The effects of 5-hydroxytryptophan (5-HTP) were studied in rats trained to press a lever under a fixed-ratio (Fr-32) schedule of water presentation. d-, l-and d,l-5-HTP all decreased responding in a dose-related manner. The levo isomer (12.5-25 mg/kg) was twice as potent as the racemic form (25-50 mg/kg) in this respect. Moderate doses of d-5-HTP (less than 100 mg/kg) did not affect responding, whereas 200 mg/kg produced almost complete suppression. The response decrement produced by 25 mg/kg l-5-HTP was completely antagonized by pretreatment with either 50 mg/kg or 400 mg/kg of the decarboxylase inhibitor, benserazide (Ro4-4602). The specific peripheral decarboxylase inhibitor, carbidopa (MK-486) (50 mg/kg) and the peripheral serotonergic antagonist, xylamidine tosylate (1 mg/kg) also antagonized the effects of 25 mg/kg l-5-HTP. These results suggest that at least some of the behavioral effects of 5-HTP are due to increases in levels or turnover of 5-HTP in peripheral serotonergic neuronal systems.


The recognition and prevention of border zone cerebral ischaemia during cardiac surgery. Four patients who sustained bilateral occipital and parietal lobe ischaemia during cardiac surgery for coronary artery bypass are described. The features include cortical blindness, visual disorientation, disturbances of reading and constructional dyspraxia. The symptoms tended to improve over about six weeks and good visual acuity was regained in all instances. The likeliest cause is generalized cerebral hypotension. Ischaemic injury might be prevented by prior detection of extracranial arterial disease and by monitoring cerebral as well as cardiac activity during surgery.


Chronic lymphocytic leukaemia with subsequent development of multiple myeloma. Evidence of two B-lymphocyte clones and of myeloma-induced suppression of secretion of an M-component and of normal immunoglobulins. In a patient with chronic lymphocytic leukaemia, two M components of the IgGkappa and IgGlambda classes were demonstrated in the serum at the time of diagnosis. The patient was first followed without treatment; after 18 months multiple myeloma developed. At that time, immunofluorescence study of lymphocytes of the peripheral blood showed mainly membrane-bound immunoglobulins (S-Ig) of the IgGkappa class. The bone marrow disclosed a definite predominance of plasma cells with cytoplasmic IgGlambda, suggesting that the two B cell-derived diseases had arisen from two different cell clones. During the development of multiple myeloma, the serum concentration of the M component IgGlambda increased. Concurrently, the M component of IgGkappa gradually disappeared from the serum, and the concentrations of the normal immunoglobulins IgA and IgM declined. Following cytostatic treatment, the concentration of the myeloma-derived M component IgGlambda was halved and simultaneously the M component IgGkappa reappeared in the serum. To our knowledge, this case is the second reported of chronic lymphocytic leukaemia and multiple myeloma indicating development of the two diseases from different cell clones, and the first reported cases with myeloma-induced suppression of M-component secretion from malignant cells.


Non-specific acid esterase activity in rat lymphocytes. In a first night's collection of rat thoracic duct lymphocytes B- and T-cells were distinguished on cytocentrifuge smears by complementary markers: B-cells by rosette-formation with Staphylococcus aureus Strain Cowan 1 armed with rabbit antiserum to rat F(ab')2 and T-cells by high uptake of 3H-uridine demonstrated by autoradiography. On incubation of the cytocentrifuge smears for demonstration of alpha-naphthyl-acetate esterase (ANAE)-activity, most B-cells showed large, intense colour deposits often located in the uropod. T-cell ANAE-activity on the other hand was variable, possibly due to variations in experimental conditions. When present, the T-cell colour deposits were small, dot-like and of low intensity. ANAE-activity may then be used to differentiate between rat T- and B-cells, being a marker for the latter cell type. This is unexpected as others have reported that ANAE-activity is specific for T-cells in mouse and man. Studies with inhibitors indicate that the rat B-cell enzyme belongs to the acetylesterases.


Different requirements for T cells responding to various doses of concanavalin A. Con A is known to activate T cells to proliferation and the development of effector cells. Conflicting reports have been published as to the need for accessory cells in the T-cell response induced by Con A. We have found that the proliferative response in purified mouse spleen T cells induced by various doses of Con A requires different culture conditions and helper cells. The Con-A-induced response induced by optimal and high concentrations of the ligand requires the presence of either serum or adherent cells obtained from the peritoneal cavity or the spleen. For induction of a proliferative response by low doses of Con A both serum and helper cells must be present. The T-cell response to suboptimal concentrations of Con A is further characterized by the fact that the presence of an Ia-positive cell is required. Removal of Ia-positive cells from purified T cells results in a loss of the response of remaining cells to low doses of Con A but has less effect on the response induced by higher concentrations of the activating ligand. The possibility that distinct subsets of T cells are responding to low and high concentrations of Con A will be discussed.


A chemical approach to the mechanism of B-lymphocyte activation. II. The pure presentation of haptens does not inactivate B lymphocytes. Dinitrophenyl (DNP)-lysine-polymethylmethacrylate and DNP-cellulose conjugates do not irreversibly inactivate anti-DNP antigen-sensitive cells, regardless of the dose (up to 10 mg) or persistence of the stimulation (up to 2 weeks). Since these conjugates constitute pure hapten presentations, it is concluded that the pure hapten presentation to B lymphocyte does not irreversibly inactivate them. When murine spleen cells are cultured with Escherichia coli lipopolysaccharide (LPS) and (non-immunogenic) DNP-lysine-polymethylmethacrylate or (non-immunogenic)  DNP-cellulose conjugates, an anti-DNP immune response occurs. However, replacement of DNP-lysine-polymethylmethacrylate with polymethylmethacrylate, or DNP-cellulose with cellulose, also results in a similar anti-DNP response. It is consequently concluded that the anti-DNP responses are entirely elicited by LPS, the hapten Dnp being inoperative. The anti-DNP response elicited by DNP-Ficoll is, upon exhaustive testing, carrier-dependent. This implies that the mechanism of DNP-Ficoll immunogenicity is not two cooperative signals passed on to B lymphocytes via the hapten DNP. These results argue against any two-signal model of B-lymphocyte activation.


Study of the immunological status of patients with pulmonary tuberculosis. Most patients with pulmonary tuberculosis have impaired T-lymphocyte function as measured by dinitrochlorobenzene (DNCB) sensitization and response to tetanus toxoid. The humoral immune response as gauged by the ability to respond to typhoid vaccine was not affected. Tuberculous patients had higher immunoglobulin levels than normal controls. The relative proportions of T lymphocytes in patients were lower than in controls while those of B lymphocytes were normal. By these criteria, rifampin treatment did not seem to cause immunosuppression.


Many bacterial species are mitogenic for human blood B lymphocytes. Thirty bacterial species were tested for their ability to stimulate to increased DNA synthesis in human blood lymphocytes. A definite stimulation was obtained with eighteen bacterial species. For three of these species ten different strains of each were tested, and all increased DNA synthesis. The maximum response was after 3--4 days of culture, suggesting a mitogenic effect. This was confirmed by the induction of polyclonal antibody production shown by a plague assay, which was positive for nine of eleven species tested. Most bacterial species increased the DNA synthesis in B-lymphocyte-enriched and unseparated lymphocytes but had negligible activity on T-lymphocyte-enriched cultures. Among bacteria with a mitogenic effect and ability to induce polyclonal antibody production are Staphylococcus aureus strain Cowan I with a high content of protein A and many common human pathogens such as Haemophilus influenzae, Mycobacterium tuberculosis, Neisseria gonorrhoeae, Streptococcus group A and Streptococcus pneumoniae.


Intramural oesophageal cyst with massive mediastinal bleeding. A case report. Intramural oesophageal cysts lined by ciliated columnar epithelium are considered to be lesions which are not prone to serious complications except infection. In contrast to this view, a case of intramural oesophageal cyst recently operated upon by us, in which severe mediastinal bleeding developed, is described.


Postoperative serum level and urinary excretion of magnesium following heart surgery. The level of serum magnesium was examined in relation to open-heart surgery. A significant fall below normal values was observed during the first postoperative day, probably caused by haemodilution during bypass. Serum concentrations were normal from the second postoperative day onwards. This result differs from observations at other centres. Two possible causes for this divergency are suggested: (1) a habitiually high dietary intake of magnesium from the drinking water and (2) a postoperative regime emphasizing the maintenance of a positive blood and plasma balance, thus supplying the patients with a considerable amount of magnesium. It is concluded that no indications for pre- , per- or postoperative supplementation of magnesium in association with cardiopulmonary bypass were found.


[Echocardiographic serial study on movements of the interventricular septum after aorto-coronary bypass]. The data presented show that echocardiographically detected abnormal septal movement is frequent early after coronary bypass surgery but that these abnormalities decrease in many patients during late follow-up. Increased anterior movement of the whole heart during systole and decreased regional myocardial contraction both contribute to the septum abnormalities. However, the overall left ventricular function remains unchanged after coronary bypass surgery.


Serotonin shifts the phase of the circadian rhythm from the Aplysia eye. A putative neurotransmitter, serotonin, may be used to transmit temporal information in the eye of Aplysia, because it can shift the phase of the circadian rhythm of spontaneous optic nerve impulses from the eye and the eye contains a significant quantity of serotonin. Serotonin acts either directly on the cell, or cells, containing the circadian pacemaker or on cells electronically coupled to the pacemaker cells.


Dichromatic color language: "reds" and "greens" don't look alike but their colors do. When protanopes or deuteranopes arrange the Farnsworth Dichotomous Test colors in order of similarity, they reveal their lack of red/green hue discriminations by alternating chips that the normal trichromat sees as reddish and greenish test colors. The dichromatic orderings follow a systematic variation in saturation of blue hues through neutral and into yellow hues as described by theory for each of the two types. Some dichromats who show the typical test behavior nevertheless use reddish and greenish hue terms appropriately when instructed to name the same test colors. Lightness cues are probably used by these dichromats in the naming task but ignored in the perceptual similarity task. Thus, unlike normal trichromats, who use similar names for perceptually similar colors, dichromats may use dissimilar names for perceptually similar colors. In this way they can achieve concordance with the normative language system despite its discordance with their impoverished color perceptions.


Diverticular disease of the colon: surgical management at a military hospital. A recent review of the surgical management of diverticular disease of the colon included 73 patients. One-stage resections were accomplished in 67%, primarily in patients operated on electively for recurrent diverticulitis or fistula, and in the group of patients with cecal diverticulitis operated on for presumed appendicitis. Single-stage resection with ileorectal anastomosis is also preferred in patients with massive diverticular bleeding. For patients with large abscesses or diffuse peritonitis a two-stage procedure which removes the site of disease in the initial operation is recommended. There were no deaths and a lower incidence of complications in the group of patients who had elective operations for recurrent diverticulitis and fistula.


Hemophilus influenzae f cellulitis with bacteremia, peritonitis, and pleuritis in an adult with nephrotic syndrome. Hemophilus influenzae f was responsible for cellulitis with bacteremia, pleuritis, and peritonitis in an adult patient with the nephrotic syndrome. The patient rapidly responded to ampicillin. H influenzae f has previously been rarely found to cause pleuritis and bacteremia, but has not been reported as a cause of cellulitis or primary peritonitis. Patients with the nephrotic syndrome are prone to serious infection with encapsulated bacteria. The relative frequency of infection with the various encapsulated bacteria most likely parallels that of colonization by these organisms.


Etopic pregnancy causing massive rectal bleeding. A case of severe rectal bleeding due to an ectopic pregnancy in the wall of the cecum is reported. The usual preoperative studies for rectal bleeding were performed but did not yield a definitive diagnosis. At laparotomy the right side of the uterus was found to be adherent to the cecum.


Bulging (sagging) fissure sign in Hemophilus influenzae lobar pneumonia. A bulging fissure sign was noticed on chest roentgenogram in a patient with H influenzae pneumonia. This sign is usually associated with Klebsiella pneumonia and has also been seen in pneumococcal and plague pneumonia, tuberculosis, mass lesions of the lung, and large lung abscesses. This is thought to be the first report of a bulging fissure sign associated with pneumonia due to H influenzae.


Hereditary multiple exostoses. A rare cause of spinal cord compression. A case of hereditary multiple exostoses (HME) with compression of the cervical cord, the cervical plexus, and the ulnar nerve is reported. Complete recovery following surgery was obtianed. Review of the literature revealed 21 previous cases of HME with cord compression. The cervical and thoracic areas are predominantly affected and the symptoms usually evolve slowly. Recovery after laminectomy is to be expected in the majority of the cases.


The treatment of hemorrhagic gastritis with cimetidine. Thirteen patients in whom bleeding from hemorrhagic gastritis was not controlled by a variety of therapeutic modalities were treated with cimetidine. Twelve of the 13 patients stopped bleeding. Three subsequently rebled, two of whom required an operation to control the bleeding. The average amount of blood transfused per patient before treatment with cimetidine was 16 units and after cimetidine, 1.6 units. Nine of the 13 patients died, but only one of them died of hemorrhage. The remaining eight patients died of a combination of sepsis and multiple organ failure. We observed no adverse side-effects after the administration of cimetidine. Cimetidine is a safe and reliable means to control bleeding from hemorrhagic gastritis. Once the diagnosis of hemorrhagic gastritis is established, treatment with cimetidine should be begun and continued until the underlying stress which initiated the bleeding is controlled.


Optimal myocardial protection.

Optimal myocardial protection. The low mortality and perioperative infarction rates for aortocoronary bypass (ACB) make them unsuitable for evaluating the adequacy of myocardial protection. Enzymatic and functional measurements were found to be sensitive and specific indicators of myocardial injury. A prospective concurrent study of 78 patients undergoing triple ACB was conducted to evaluate the effectiveness of three popular methods of myocardial protection. Group I (32 patients) had a single dose of cold (4 degrees C) potassium cardioplegic (CPC) solution infused inducing a mean myocardial temperature (MMT) of 31 +/- 4 degrees C/min. Group II (23 patients) had multiple doses of CPC solution 8nducing a MMT of 22 +/- 2 degrees C/min. Group III (23 patients) had intermittent anoxic arrest at a MMT of 28 +/- 1 degrees C. The groups were not randomized but had comparable clinical symptoms and catheterization findings. Serial measurements of cardiac specific creatine kinase (CK-MB) revealed a peak in enzymatic activity occurring 60 minutes following ACB. The highest CK-MB was significantly (P less than 0.01) lower in group II (25 +/- 8 IU/liter) than group I (50 +/- 8 IU/liter), or group III (68 +/- 14 IU/liter). Myocardial performance was evaluated after ACB by serially measuring left ventricular stroke work index (SW) and left atrial pressure (LAP) in response to volume loading. The rise in SW was significantly (P less than 0.01) greater in group II (3.0 +/- 0.7 gm.m/sq m/mm Hg) than in group I (1.4 +/- 0.7) or group III (1.8 +/- 0.9). The highest SW attained was higher (P less than .01) in group II (43 +/- 7 gm.m/sq m) than group I (19 +/- 6) or group III (34 +/- 8) at comparable LAP values (group I: 20 +/- 5 mm Hg; group II: 18 +/- 3; group III: 18 +/- 4). Post-operative clinical evaluation failed to differentiate among the three groups. The more sensitive indices, however, demonstrated the superiority of cold, multidose cardioplegia in providing optimal myocardial protection.


[Abolition of pacing induced akinesia after aorto-coronary bypass grafting in patients with stable angina (author's transl)]. Hemodynamic studies were performed in 6 normal individuals, 8 patients with severe obstruction (more than 85% stenosis) of the left anterior descending coronary artery (LAD), 10 patients with patent LAD grafts and 4 patients with stenosed or occluded LAD grafts. All patients were suffering from stable angina before operation. Monoplane ventriculograms and left ventricular pressure determinations were carried out at rest and immediately after ventricular pacing (170/min.). Anterior wall motion was determined from half-diameter shortening and ejection fraction was calculated using the area-length method. Heart rate and left ventricular systolic pressure were comparable in all 4 groups at rest and after pacing. Normal individuals and patients with patent grafts to the LAD showed no significant change of anterior wall motion, ejection fraction and left ventricular enddiastolic pressure after pacing as compared to rest. Patients with LAD stenosis showed a significant decrease of anterior wall motion, of ejection fraction and an increase of left ventricular end-diastolic pressure. Patients with graft failure revealed a drastic though not significant decrease of anterior wall motion. Decrease of ejection fraction and increase of left ventricular end-diastolic pressure were significant. Thus, in patients with stable angina and severe coronary stenosis regional and total left ventricular function may well be maintained at rest but become severely impaired after pacing. Successful revascularization abolishes this ischemic response.


Stimulatory effect of soluble supernatant on hydroxylase activity of rat testis microsomes. Addition of soluble supernatant to testis microsomes results in 42% increase in steroid 17,20-lyase activity and a 65% increase in 17alpha-hydroxylase activity. This stimulatory activity could be partially purified by salt fractionation. The activating factor(s) was not removed by dialysis nor did it appear to be lipid. It was destroyed by trypsin. Differential effects of heat were observed with the hydroxylase and lyase activators. The activation did not affect Km but only increased Vmax. The supernatant could be added to each enzyme to the point of maturation. No binding of steroids by the supernatant could be detected. Corpus luteum and placental supernatant did not stimulate enzymic activity, but supernatant from an adrenal adenoma was active.


The transition from natural to controlled fertility in Taiwan: a cross-sectional analysis of demand and supply factors. Three factors are usually proposed as inducing the transition from natural to regulated fertility. Fertility regulation may occur when the demand for children is reduced; when general attitudes toward fertility regulaton become positive; and, finally, when such factors as infant and child survival prospects and natural fertility conditions improve. Applying the Easterlin framework for fertility determination, this paper considers the effect of these factors in the shift from natural to regulated fertility in Taiwan in 1965. Cross-sectional data for continuously married women aged 35-44 are used. The results indicate that, at the initial stages of the fertility transition, it is primarily an increase in the potential output of surviving children and a decline in the subjective costs associated with fertility regulation, rahter than a decline in desired fertility, that distinguish the natural fertility subpopulation from the regulating subpopulation.


[Neuropathological aspects of chronic diseases]. Practically all diseases of bodily organs may lead to quantitatively and qualitatively differing alterations of the central and periphal nervous system. These are connected to the basic disease on one side, to compications on the other. The preliminary condition for the appearance of encephalopathies following bodily diseases lies mostly in a disturbance of the blood-brain and blood-liquor barrier. No close correlation exists usually between psychiatric and nervous syndromes and pathomorphological findings. However, the findings are often characteristical, although not specifical. Especially the findings in uraemia, liver diseases, rheumatic and so-called pararheumatic diseases (collagenoses) are discussed.


[Pathogneses of cutaneous malignant lymphoma]. In 1974 we suggested a schedule of the pathogenesis of CML. CML was described as a variant of the cutaneous lymphadenoid infiltrate (Fig. 2). Four years later, the schedule still appears to be valid, even to explain the three types of pseudolymphoma (Table 3). Recent findings concering. Burkitt's lymphoma and Mycosis fungoides fit in well with the proposed schedule. In studying CML recognition of the malignant lymphomatous cell is most important. Progress in immunology should make it possible to destroy these malignant cells by immunological measures since the cells belong to one clone.


Juvenile cirrhosis and membranous glomerulonephritis in a child with alpha1-antitrypsin deficiency PiSZ. An infant with alpha1-antitrypsin (alpha1-AT) deficiency PiSZ presented with liver cirrhosis and showed clinical and laboratory evidence of renal disease when hepatic decompensation developed, shortly before death at 12 months of age. Low serum levels of alpha1-AT were only demonstrated late in the disease. SZ phenotype was proved by starch gel electrophoresis. Post-mortem pathological studies revealed severe hepatic cirrhosis with intracytoplasmic inclusion of alpha1-AT and membranous glomerulonephritis with deposits of complement and immunoglobulins but without the presence of alpha1-AT. The present case suggests the importance of studying Pi phenotypes and serum levels of alpha1-AT in all cases of idiopathic cirrhosis or renal disease in infancy.


[Neurophysiologic analysis of activation spontaneously developing in Rana temporaria frogs against a background of primary sleep]. The presence of spike-like activity against the background of the primary sleep EEG is described in the frog. Patterns of amplitude--frequency spectra computed for parts of the EEG with this activity differ from those computed for the typical EEG of the primary sleep, but have much in common with the spectra of wakefulness EEG. The point of view suggested by I. Karmanova [8] about functional role of different forms of activation arising against the background of the primary sleep in poikilotherms as possible precursors of paradoxical sleep in homoiotherms is confirmed.


Intranuclear cytoplasmic organelles in hematopoietic diseases. Mitochondria, rough endoplasmic reticulum, Golgi apparatus and other cytoplasmic organelles were found within the nuclei, not in 'nuclear pseudo-inclusions', of some cells in several hematopoietic disorders. Mitoses were fairly often observed in the atypical cells of these cases. We suggest that these intranuclear cytoplasmic organelles may be trapped in the nucleus during an abnormal mitosis.


[Vasomotor innervation of the arteries and veins of Rana temporaria frogs]. Adrenergic and cholinergic innervation of frog arteries and veins has been studied histochemically using glyoxilic acid and the method of Karnovsky--Roots. It was shown that the vessels studied differ in catecholamine-containing structures, the intensity of fluorescence of adrenergic nerve endings, the density of nervous plexus and the direction of nerve fibers. It was found that adrenergic innervation is present not only in the arteries, but in the veins as well. Morphometrical analysis indicates that the density of adrenergic plexus per volume unit of vascular wall in the veins investigated is higher than the density of adrenergic nerves in the arteries. This finding suggests that the nervous control of the veins appears in evolution beginning from amphibians, but not from reptiles. It was reliably demonstrated that aorta thoracica and pulmonary artery receive cholinergic innervation, the density of cholinergic plexus in the latter being twice higher than that of adrenergic one.


[Human serum colony-stimulating factor in mouse bone marrow culture]. Activity of CSF was measured in human serum after chromatography on Sephadex G-200. Agar culture of bone marrow cells was done in Petri dishes with agar in Eagle'a medium containing fetal calf serum and antibiotics. This agar-medium containing mouse bone marrow cells, was allowed to gel and the dishes were incubated at 37 degrees C in a fully humidified atmosphere of 10% CO2 in air. Our data indicate that chromatography procedure allows to get CSF free from its inhibitors. All activity was localized in one peak, in the region of low molecular weight proteins.


Mitogen stimulation and distribution of T- and B-lymphocytes during natural rubella infection. The phytohaemagglutinin (PHA) response of lymphocytes from seven patients with natural rubella infection was investigated during the acute, early and late convalescence stages of disease. When the lymphocytes were cultured in autologous serum, a moderate depression of the response, following stimulation with PHA in both optimal and suboptimal concentrations was obtained two weeks after the onset of exanthema (early convalescence). Two months later (late convalescence), the lymphocyte stimulation response had returned to almost normal values. On the other hand, lymphocytes incubated in pooled homologous serum reacted normally to PHA in optimal concentrations at all three stages. Determination of T- and B-lymphocytes did not reveal any change in the relative proportion of T-lymphocytes during the course of the disease. However, in late convalescence, a significant decrease in the relative number of B-lymphocytes was recorded.


Characterization of clinical tonsil stages by their T-cell count. Immunopathological description of tonsils after a peritonsillar abscess. The T-cell counts in five different clinical tonsil stages are compared. No particularities were observed, with the exception of the condition after a peritonsillar abscess. The differences existing between the individual groups are discussed as age-dependent. A considerable increase in T-cells is found in the abscess tonsil compared with other tonsils and the T-cell count in blood. Its pathomechanism is discussed.


The prevalence of IgE antinuclear antibodies in rheumatoid arthritis and systemic lupus erythematosus. Antinuclear antibodies (ANA) of the IgE class were studied in sera from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and healthy controls. Sixty per cent of 20 RA patients with neutropenia were found to have IgE granulocyte-specific (GS-)ANA, whereas only 16% of RA patients without neutropenia had IgE antibodies of similar specificity. About 5% in each group of RA patients had IgE organ-nonspecific (ON-)ANA. Eleven of 15 patients with active SLE and only 4 of 20 with inactive SLE had IgE ON-ANA. Sera from five patients with lupus nephritis all contained IgE ON-ANA. None of 100 sera from controls showed presence of IgE  ANA. IgE ANA titres in RA and SLE patients correlated to the titres of ANA of the other four immunoglobulin classes. Gel filtration studies at neutral and acid pH of RA sera containing high titres of IgE GS-ANA indicated the presence of these antibodies in immune complexes. Studies of serum cryoprecipitates supported this conclusion. IgE ANA production may be of pathogenetic importance in RA and SLE by eliciting type-I reactions.


Schizophrenia and rheumatic disease. A study on the concurrence of inflammatory joint diseases and a review of 58 case-records. The coincidental occurrence of schizophrenia and rheumatoid arthritis is considered to be low in relation to the prevalence of the two diseases. In the present study, data from the patient statistics prepared by the Swedish Social Welfare Board were examined for the occurrence of rheumatic disease in schizophrenic patients. With the aid of the statistics and of questionnaires, 58 case-records were collected and studied. Very few cases were found of co-existing schizophrenia and inflammatory joint disease, rheumatoid arthritis in particular. There were, however, some cases of genuine schizophrenia and definite seropositive rheumatoid arthritis in the same patient. Rheumatoid arthritis is possibly uncommon also in combination with other psychiatric diseases that require hospital care. The ankylosing-spondylitis cases were over-represented in relation to the rheumatoid-arthritis cases included in the statistics from psychiatric care. Most of the 13 ankylosing-spondylitis patients whose case-records were studied had schizoaffective psychosis or atypical psychosis. The results of the investigation should be confirmed by epidemiological studies; this may contribute to the understanding of the aetiology of rheumatoid arthritis and of schizophrenia.


Natural history and life expectancy in severe alpha1-antitrypsin deficiency, Pi Z. Clinical data from 246 adult Swedish individuals with severe alpha1-antitrypsin deficiency, Pi Z, diagnosed in 1963--77, were analyzed. Primary emphysema was present in 109 cases. Of 75 Pi Z patients with other types of chronic obstructive pulmonary disease (COPD), all but 7 showed signs of emphysema. Median age at onset of dyspnoea in Pi Z smokers was 40 years, compared to 53 in non-smokers (p less than 0.001). Of the Pi Z individuals over the age of 50, 19% had a diagnosis of liver cirrhosis and 15% signs of glomerular renal damage. Of 91 deceased patients, 56 died from COPD and 12 from liver disease. A greatly reduced survival was demonstrated in Pi Z individuals, regardless of sex. Smoking Pi Z individuals had a significantly lower life expectancy than Pi Z non-smokers (p less than 0.01).


Intermediate alpha1-antitrypsin deficiency, Pi M-. A 50-year-old man was found to have 40% of the normal serum alpha1-antitrypsin concentration but subsequent electrofocusing showed a pattern indistinguishable from the ordinary M pattern. This finding and family studies suggested that he was a carrier of a null (-) allele. Heavy smoking and this Pi M- phenotype in interaction probably were responsible for the development of emphysema, documented by an extensive investigation of lung function. Two non-smoking offspring carrying the null allele had normal lung function. Normal karyotypes were found in all the Pi M- subjects.


Ventriculographic features of ascending transtentorial herniation. The ventriculographic findings of a severe ascending transtentorial herniation that occurred after shunting in an infant with a posterior fossa tumour are described.


Activation of B cell subsets by T-dependent and T-independent antigens. The capacity of the trinitrophenyl haptenic group coupled to a series of chemically dissimilar carriers to cross-stimulate putative T-dependent and T-independent B-cell subpopulations was determined by using an in vitro limiting dilution technique to generate primary IgM responses. TNP-Ficoll and TNP-dextran, two T-independent antigens with little or no polyclonal mitogenicity, stimulate the same population of anti-TNP precursors, which is distinct from the precursor population activated by TNP-LPS, a T-independent polyclonal mitogen, or by TNP-HRBC, a T-dependent antigen. TNP-LPS and TNP-HRBC activate the same precursor population, indicating that LPS can substitute for the T cell signal in T-dependent B-cell responses, whereas nonmitogenic T-independent antigens cannot. However, the cumulative evidence from this and other laboratories suggests that LPS and T-dependent antigens activate B cells by different mechanisms. TNP conjugates of Ficoll and dextran, which are relatively poor inducers of polyclonal B cell activation, induced larger anti-TNP clones than did TNP-LPS, a strong polyclonal mitogen. Macrophages are required for the anti-TNP-Ficoll/anti-TNP-dextran response, whereas, a similar requirement has not been shown for the anti-TNP-LPS response. Thus, macrophages may function as polyclonal B cell activators in T-independent responses. Experiments in which TNP was coupled directly onto the macrophage surface support this hypothesis. B-cell heterogenity in T-dependent responses is suggested by experiments using the C3 receptor as a marker for functional subpopulations of B cells. Murine T cells cooperate with B cells that carry a receptor for C3 and with at least some B cells which lack the C3 receptor in a primary in vitro antibody response. In vitro culture experiments using populations of B cells fractionated on the basis of the C3 receptor showed that CR+ cells were unable to make T-dependent antibody responses in the presence of anti-C3 antibody, whereas the response of CR- B cells was unaffected. Using irradiated, carrier-primed spleen cells from B10.A mice as a source of helper cells for B cells derived from various congenic strains in an in vitro primary IgM response to TNP-KLH, CR+ B cells cooperated across haplotype differences in the I region of the MHC, whereas CR- B cells did not. Preliminary mapping experiments for the genetic restriction of CR- B cells suggest complementation between the I-A and I-C subregions of the MHC. These findings tentatively suggest the existence of alternative cooperative pathways between T cells and B cell subpopulations.


Regulation of anti-hapten antibody secretion by carrier-specific suppressor T cells. Carrier-primed T lymphocytes can suppress high avidity IgG anti-hapten antibody secretion within 90 min. in vitro if the suppressor and target cells are primed with the same carrier determinants. Suppression seems to be directed to the antibody secreting cell since the effect is rapid and does not depend on macrophages or T cells in the target cell population. Suppression can be blocked by inclusion of soluble carrier in the cell mixture or by treatment of the target cells with anti-carrier antibody or pronase. Moreover, suppression can be augmented by PFC exposure to the soluble hapten-carrier conjugate. Finally, carrier specificity may be altered by preincubation of the target population with a hapten-heterologous carrier before addition of suppressor cells specific for the heterologous carrier. Thus, it is likely that high avidity suppression depends upon immunogen bound to the surfaces of antibody secreting cells which serves as a target for suppressor cells or molecules.


Independent precursors for thymus dependent and thymus independent IgG memory B cells. Spleen cells from mice primed with the thymus dependent antigen trinitrophenyl keyhole limpet hemocyanin several months earlier can be cultured in vitro to give vigorous IgG antihapten PFC responses to thymus dependent and thymus independent forms of the hapten. The IgG memory precursors responding to these two forms of the hapten constitute functionally distinct subpopulations which we have designated as B1gamma and B2gamma to represent the precursor cells responding to the thymus independent and thymus dependent antigens respectively. Four types of evidence for these subpopulations are presented 1) the responses to the two types of antigen are additive when both forms are added to the same culture; 2) the precursor frequency for the thymus dependent and thymus independent populations is different although expansion over primary IgM precursor frequencies was not detectable; 3) the avidities of the PFC elicited by each antigen are distinct; the thymus independnet antigens elicit lower avidity PFC; 4) selective killing of one population can be accomplished by BUdR and light treatment without affecting the other population.


Radionuclide assessment of ventricular performance during propranolol withdrawal prior to aortocoronary bypass surgery. The effects of oral propranolol upon left ventricular performance were assessed in 18 patients with angiographically documented coronary artery disease in whom propranolol was tapered prior to elective aortocoronary bypass surgery. Left ventricular ejection fraction, ejection rate, and regional wall motion were obtained on three occasions with first-pass radionuclide angiocardiographic techniques. Patients were studied at peak propranolol dose ( +/- SEM) 224 +/- 29 mg./day; serum propranolol level, 85 +/- 22 ng./ml.), intermediate dose (99 +/- 9 mg./day; serum propranolol, 30 +/- 6 ng./ml.), and 24 hours following discontinuation of propranolol therapy. Heart rate increased significantly (62 +/- 2.3 vs 67 +/- 3.0 vs 73 +/- 2.3 beats/minute, p less than 0.001) during propranolol withdrawal, while systolic blood pressure did not change significantly (114.7 +/- 4.3 vs 110.3 +/-3.0 vs 113 +/- 3.0 mm. Hg, p greater than 0.05). There was no significant change in ejection fraction (59.1 +/- 2.4 vs 60.4 +/- 2.0 vs 59.2 +/- 2.5 per cent) or ejection rate 2.80 +/- 0.18 vs 2.87 +/- 0.18 vs 2.92 +/- 0.20 sec.-1) as propranolol was tapered (p greater than 0.05). No patient demonstrated a change in regional wall motion in response to propranolol withdrawal. The results of this study suggest that oral propranolol in commonly used clinical dosages does not significantly affect radionuclide measures of left ventricular performance in the basal state.


Transcatheter therapy of gastrointestinal arterial bleeding. Transcatheter therapy for arteriocapillary gastrointestinal bleeding is often an effective form of treatment. The choice of transcatheter therapy (ie, vasoconstrictor or occlusive) often is dependent on the etiology and location of bleeding. Vasopressin is a generally safe form of treatment which is often successful in treating bleeding secondary to gastritis, Mallory-Weiss mucosal tears, and diverticular disease. It is less effective in treating bleeding peptic ulcers, neoplastic bleeding, or bleeding when clotting abnormalities exist. Occlusive therapy is an effective alternate form of therapy in selected circumstances. Ischemic complications from vasoconstrictor and embolic therapy may occur and require appropriate caution and discretion with their use.


Giant cell carcinoma of the pancreas. Report of a case with upper gastrointestinal bleeding diagnosed by endoscopic brush cytology. A case of upper gastrointestinal bleeding as the first and only manifestation of giant cell carcinoma of the pancreas invading the duodenum is described. The polypoid tumor was visualized during endoscopy. The diagnosis was made by a cytologic brush and confirmed by endoscopic biopsy. The rather uncommon presentation of pancreatic carcinoma and the possibility of establishing the diagnosis by a cytologic brush is discussed.


T and B lymphocytes, immunoglobulins and complement components in bronchial asthma. Sixty children, 7--15 years old, suffering from bronchial asthma and 44 healthy children, 12--14 years old, were studied for the percentage and the total count per mm.3 of T and B lymphocytes. Patients were classified into extrinsic atopic, mixed and intrinsic asthma. According to the clinical course mild and severe cases were analysed separately. The total and "active" T lymphocytes were detected by the ability to form nonimmune rosettes with sheep red blood cells. The B lymphocytes were estimated by the rosetting procedure with antibody mouse complement coated sheep erythrocytes. No decrease of the percentage or total count of T lymphocytes was observed, and an elevation of total count and percentage of active T cell rosettes was even seen in severe cases of extrinsic atopic asthma. The B cell percentage was decreased in severe atopic, mild intrinsic and mild mixed asthma but the total number was lowered only in the last group. The immunoglobulin A, G, M, D and E level, measured by the single radial immunodifussion test, was correlated neither to T cell nor B cell percentage. The complement components C1q, C4, C3, C3 proactivator and C5 were measured by the radial immunodufusion test in the plasma of some patients and controls. The C1q level was normal. An elevation of C4 in mild extrinsic, C5 in severe extrinsic and C3 in severe mixed asthma was seen. A decrease of C3 proactivator was observed in mild extrinsic and mixed asthma, and in three cases of intinsic asthma this was accompanied by lowering of C3, suggesting an activation of the alternative pathway.


Triplo-X constitution of mother explains apparent occurrence of two recombinants in sibship segregating at two closely X-linked loci (G6PD and deutan). Two male sibs believed to be examples of meiotic recombinants between the closely linked loci for G6PD deficiency of Mediterranean type and severe deutan color blindness proved to be simple segregants of a triplo-X mother of genotype d--GdMediterranean/d+GdMediterranean/d+GdB. This finding suggests that in Sardinia the linkage between the two loci under consideration may be tighter than previously assumed.


Alpha1-antitrypsin: further genetic heterogeneity revealed by isoelectric focusing. Alpha1-antitrypsin is a major human serum protein that shows an extensive polymorphism. Genetic heterogeneity has previously been demonstrated by starch gel electrophoresis. By applying analytical isoelectric focusing (pH 3.5--5.0) to this system, we found a common variant, Pi M3, with an isoelectric point between those of Pi M1 and Pi M2. The gene frequency of this variant was .11 in U.S. whites and .054 in blacks. When PiM3 and PiM1 are included in the Pi system, the heterozygosity at the Pi locus is five times greater in whites and 10 times greater in blacks than that detected by earlier electrophoretic techniques.


Human pancreatic alpha-amylase: phenotypic codominance and new electrophoretic variants. The genetic heterogeneity of human pancreatic alpha-amylase (alpha-1,4-glucan 4-glucanohydrolase, E.C. 3.2.1.1) has been better defined through the development of an asparagine buffered electrophoretic gel system. Three alleles had been identified for the pancreatic amylase locus, AMY2, with two variant alleles as autosomal dominant traits on Tris HCl buffered sheet gels. The asparagine buffered sheet gel now allows the differentiation of the genotypes AMY2B/AMY2B,AMY2B/AMY2A, and AMY2B/AMY2C, thus classifying these three alleles as codominants. Asparagine buffered polyacrylamide gels and thin layer polyacrylamide isoelectric focusing aided in the identification of three new pancreatic amylase variants: AMY2D,AMY2E, and AMY2F. AMY2E has been identified only in AMY2B and AMY2E individuals. This allele is proposed as a quantitative activity variant with essentially the same electrophoretic mobility as AMY2A. The other new autosomal variants have each been identified in single white families. AMY2D is dominant and AMY2F is a codominant trait as shown on thin layer polyacrylamide isoelectric focusing gels.


The HLA antigens in Cogan's syndrome.

The HLA antigens in Cogan's syndrome. HLA typing of ten patients with well documented Cogan's syndrome failed to support previous reports of an increased incidence of HLA-B17. Although HLA-A9 (Aw24), Bw35, and Cw4 appeared increased in frequency among patients, the small number of cases precluded attaching importance to the significance of these increased frequencies.


In vitro antibiotic synergism against ocular fungal isolates. A microtiter method for the determination of fungal sensitivities was used to determine the minimal inhibitory and fungicidal concentrations of two antifungal agents, amphotericin B and natamycin, both alone and in combination with four different antibiotics: rifampin, gentamicin, clindamycin, and tetracycline. Synergism was defined as a fourfold or greater reduction in the minimal inhibitory concentration, minimal fungicidal concentration, or both, of the antifungal agent in the presence of antibiotic; antagonism was defined as fourfold or greater increase in the minimal inhibitory concentration, minimal fungicidal concentration, or both. Amphotericin B and rifampin were synergistic against the majority of organisms, but synergism between amphotericin B and other antibiotics was infrequent. Combinations of natamycin and rifampin or of natamycin and gentamicin were synergistic against the majority of Fusarium solani tested. Combinations of amphotericin B and tetracycline were antagonistic against 14% of the organisms.


Peripheral corneal ulcers with herpes zoster ophthalmicus. Four patients with herpes zoster ophthalmicus developed peripheral corneal ulcers with steep central edges. An anterior uveitis was associated with all cases. One patient developed bilateral corneal ulcers that were typical of Mooren's ulcer and eventually destroyed both corneas. The other three cases were unilateral and were not relentlessly progressive.


Unplanned extracapsular cataract extraction in postvitrectomy eyes. A 70-year-old man, a 59-year-old woman, and a 57-year-old woman underwent pars plana vitrectomy. In all three cases, cataracts developed in the eyes that had been operated on. During cataract extraction, which included massage of the globe after retrobulbar anesthesia and a conventional ab externo incision, loss of lens material into the vitreous cavity occurred in all three postvitrectomy eyes.


Mechanisms of tumor immunity. An overview. The involvement of the immune system in the host response to tumors is complex and involves both lymphocytes and lymphocyte-derived mediators, as well as inflammatory cells and various other agents such as complement. These activies are not confined to cytodestructive processes; recent studies demonstrate that the migration characteristics of tumor cells may be modified by immunologically derived substances. The multiplicity of possible immune system-neoplastic cell interaction is unfortunately balanced by the multiplicity of mechanisms that serve to interfere with an effective immune response to tumors. These mechanisms may reflect pathologic derangements of normal immunoregulatory processes or may involve the production of suppressive substances by the tumors themselves. In either case, a number of genetic and other predisposing factors must contribute to the ultimate resolution of the battle between host and tumor. Successful strategies for immunologic intervention must take these parameters into account.


Autoimmunity and tumor resistance. 3-Methylcholanthrene tumorigenesis in New Zealand Black mice. Skin tumors induced by the subcutaneous injection of 3-methylcholanthrene (3-MC) in New Zealand Black (NZB) mice had a delayed development and lower frequency compared with BALB/c and C57BL mice. In the SJL/J strain, the incidence of tumors was lower than in the NZB, but with the same delayed development. Most of the tumors in the BALB/c, C57BL, and SJL/J strains were sarcomas; more than one third of the tumors in the NZB mice were squamous cell carcinomas. The greatest frequency and most rapid development of tumors in the NZB, as a function of age at the time of injection of 3-MC, occurred at 4 months. Young (3.5 and 7 weeks) and 12-month-old tumor incidence in the 4-month-old NZB was decreased by treatment with antithymocyte serum (ATS). Five hundred rad whole-body x-irradiation accelerated the onset of tumors but did not increase the final incidence. 3-MC injection and the presence of skin tumors had no influence on the development of glomerulonephritis or hematopoietic neoplasms in the NZB mice. Coombs' positive anemia was not influenced by 3-MC injection, but there was an earlier and increased incidence of positive Coombs' tests in tumor-bearing animals. Liver aryl hydrocarbon hydroxylase (AHH) specific activity was low in the young NZB, increased gradually with age, and was higher in the female mice.


An increase in intraocular pressure due to clonidine. The rise in intraocular pressure (IOP) observed after the administration of clonidine into the carotid arteries was studied in anesthetized rats and cats. This increase of IOP proved to be blocked by the alpha-sympathicolytic agent piperoxane and by the muscle relaxants d-tubocurarine and gallamine. Our experiments suggest that the elevation of IOP after clonidine injection is due to contraction of the eyelids and extraocular muscles. In these tissues alpha-adrenoceptors seem to play a part.


[In vitro incubation of lenses. Model for testing substrate utilization of substances of the energy metabolism, demonstrated with bencyclane-hydrogen-fumarate (author's transl)]. When bovine lens homogenate was treated with bencyclane-hydrogen-fumarate, the carbohydrate metabolism was activated. This may chiefly be due to the fumarate part of the substance. A 24 H In vitro incubation of whole bovine lenses in TC-199 with and without bencyclane-hydrogen-fumarate did not show the above effect. On the model of former investigations by J.E. Harris et al. we modified the test procedure by selecting the medium and the time of incubation so that the endogenous carbohydrates of the lens were consumed, thus creating new metabolic balances. This metabolic condition allows investigations intended to activate metabolic processes and to restore the steady state of metabolic parameters. We investigated the effect of bencyclane-hydrogen-fumarate using the same method and found that given certain conditions the lens recovers when incubated for 2 h in TC-199 (containing 1 g glucose/1) with addition of a 10(-4) M solution of bencyclane-hydrogen-fumarate. The ATP-content of these lenses in particular gives proof of this result. As already observed in former investigations on homogenates, this effect is probably due to metabolization of the fumarate part of the bencyclane-hydrogen-fumarate by the citric acid cycle. The method used explains the differences observed when using lens homogenates or whole lenses under the same experimental conditions.


[The equidensitometric analysis of ultrasound B-scans--a possibility for the differentiation of tissues (author's transl)]. An equidensitometric method for the objective analysis of ultrasound B-scans is presented that not only allows an exact analysis of the distribution of the grey values within the B-scan, but thereby also makes the differentiation of tissues possible. The method is demonstrated and the findings in human tongues are documented.


Fluorescein angiography of the corneal limbus--drug effects on capillary blood flow. By means of fluorescein angiography, plasma flow through the capillaries at the limbus corneae is demonstrated. The number of stained capillaries at a given time served as a measure of capillary perfusion. Even without drug the entire capillary system is perfused at least by plasma. Tolazoline enhanced the velocity of perfusion (P = 2alpha less than 0.01), epinephrine caused a marked capillary constriction (P = 2alpha less than 0.01), as well as--to a lesser extent--did dexamethasone (P = 2alpha less than 0.05). Dionine caused hyperemia, but the data varied much more than after tolazoline. In addition, dionine enhanced the dye leakage from the vessels.


Effect of prostaglandin E2 on the permeability of the iris vessels to horseradish peroxidase in the rabbit. Prostaglandin E2 (0.5 microgram in 10 microliter 10% ethanol) was introduced into the anterior chambers of rabbit eyes. Using the horseradish peroxidase method, it was shown under the electron microscope that the endothelial barrier of the iris vessels broke down. The peroxidase penetrated as far as the basis of the posterior epithelial cells, however, without entering their lateral intercellular spaces. The question of whether the effect of prostaglandins on the barrier was a direct effect or at least a partially indirect one, i.e., a haemodynamic action, is discussed.


Colonoscopic evaluation of rectal bleeding: a study of 304 patients. We studied 258 patients with rectal bleeding and 46 patients with anemia and occult blood in the stool. All 304 patients had negative proctosigmoidoscopies, single-contrast barium studies that were negative or showed diverticula only, and colonoscopic evaluation. In the 258 patients, the overall incidence of finding significant lesions by colonoscopy was 41.5%. Twenty-nine patients (11.2%) had carcinoma and 17 patients (6.6%) had cecal telangiectasia. In the 46 patients, the overall incidence of finding significant lesions was 19.6%. Three patients with carcinoma were found in this group. A significant number of both benign and malignant lesions were detected by colonoscopy proximal to the splenic flexure. Colonoscopy should be done in patients with rectal bleeding or anemia and occult blood in the stool who have had negative proctosigmoidoscopies and single-contrast barium studies interpreted as normal or showing diverticula.


Telangiectasia and von Willebrand's disease in two families. Two families are described with members who have both von Willebrand's disease and telangiectasias. Family A has four members in three consecutive generations that have both von Willebrand's disease and telangiectasias. von Willebrand's disease in this family is characterized by decreased ristocetin cofactor (FVIII-vWF), variably depressed factor VIII coagulant (FVIII-AHG), and factor VIII-related antigen (FVIII-AGN) levels. FVIII-AGN mobility on two-dimensional crossed immunoelectrophoresis was found to be normal. Four generations in Family B have von Willebrand's disease characterized by decreased FVIIII-AHG, FVIII-vWF, FVIII-AGN, and prolonged template bleeding times. Two members of this family also have telangiectasias and recurrent gastrointestinal bleeding. Results in these two families suggest an association between von Willebrand's disease and telangiectasia--perhaps a defect in vascular endothelial cell function.


Allergic contact photodermatitis to para-aminobenzoic acid. Allergic photocontact dermatitis developed in a patient to a commercial sunscreen preparation containing para-aminobenzoic acid (PABA) in an alcohol base. Photopatch testing showed photosensitivity to PABA. Sensitization could only be detected when PABA was tested in an alcohol vehicle; a photopatch test to PABA in petrolatum was negative.


Cockayne's syndrome and emphysema.

Cockayne's syndrome and emphysema. A 5-year-old boy with Cockayne's syndrome is described. In addition to the recognised clinical features, he presented with severe fixed airways obstruction, and investigations confirmed clinical and physiological emphysema. In a disorder associated with many of the features of aging, it is probably that the presence of relative alpha-1-antitrypsin deficiency (1.5 g/l) in a child with PiMZ phenotype, contributed to his severe lung disease.


Pancreatic pseudocyst--operative strategy. The experience with 131 patients with 157 pseudocysts is reported. One hundred and twenty patients with 146 pseudocysts underwent 165 operations. There were ten operative deaths (8.3%) three of which were not attributable to the pseudocyst or its operative management. Sixteen patients died six months to 14 years after operation. Deaths in six of the 16 patients were in part attributable to pancreatitis or complications of pseudocyst management. The operative mortality was highest in patients undergoing incision and drainage and cystoduodenostomy. Other factors influencing mortality unfavorably included postoperative gastrointestinal hemorrhage from a pseudocyst; rupture or fistulization of the cyst into the gastrointestinal tract if associated with hemorrhage, and evidence of common duct obstruction, or the location of cysts in the head or uncinate process of the pancreas. Visceral angiography should be performed on all patients with pseudocysts. The risk of massive gastrointestinal or intra-abdominal hemorrhage is highest in the 10% of patients having pseudoaneurysms associated with their pseudocysts. Incision and drainage of pseudocysts is associated with a high rate of recurrence of the cyst and continued pain. Incision and drainage should only be used if the cyst is infected, or the cyst wall is not mature enough to hold sutures. Cystogastrostomy and cystojejunostomy are the procedures of choice for mature cysts. The presence of a pseudoaneurysm visualized on preoperative visceral angiography is an indication for an excisional operation as are the presence of multiple cysts, compression of the common duct or duodenum by the cyst, evidence of left sided portal hypertension, recurrent cysts or evidence of chronic pancreatitis.


Immune monitoring protocol for patients with carcinoma of the head and neck. Preliminary report. Numerous investigators have observed a depression of cell-mediated immunity in patients with carcinoma of the head and neck using a variety of in vitro and in vivo assays. This report presents the data obtained when a group of head and neck cancer patients were evaluated for reactivity in an in vitro lymphocyte blastogenesis assay using polyclonal mitogens and specific antigens, numbers of peripheral blood T-lymphocytes, and levels of circulating immune complexes. Such an immunological monitoring protocol revealed a depressed reactivity of the cancer patients in the lymphocyte blastogenesis assay when compared to normal age-matched controls. We also observed that 75% of these patients had circulating soluble immune complexes in their sera before and after therapy. These preliminary data indicate that further research is needed to examine the potential role of soluble immune complexes in modulating the host's immune response.


Vestibular toxicity of gentamicin. Incidence in patients receiving long-term hemodialysis therapy. Twenty-three patients on long-term hemodialysis regimens who received gentamicin sulfate were reviewed retrospectively to assess the incidence of ototoxicity and to identify potential risk factors. Dosage of gentamicin sulfate was 1.0 to 1.5 mg/kg intravenously three times weekly. Serum gentamicin levels were monitored in 21 cases. Seven patients developed signs and symptoms of vestibular dysfunction. Statistically significant differences were found between the ototoxic and nonototoxic groups with respect to age (P less than .001), total dose (milligrams per kilogram) (P less than .001), and duration of therapy (P less than .001). The total dose per kilogram of body weight contributed most heavily to ototoxicity, and regression analysis suggests that the critical cumulative dose is about 17.5 mg/kg. The two groups did not differ with respect to mean peak and valley serum levels. We conclude that this population is at high risk of developing gentamicin-related vestibular dysfunction specifically when the cumulative dose exceeds 17.5 mg/kg.


Bacteremic Haemophilus influenzae genitourinary tract infections in adults. Six cases of bacteremia associated with genitourinary (GU) tract infections in adults due to Haemophilus influenzae occurred during a 42-month period at the Health Sciences Centre in Winnipeg, Canada. Four cases were associated with pregnancy or abortion, one with acute salpingitis, and one with urinary tract manipulation. Four of the five strains available for serotyping were nontypable. Clinical conjunctivitis was present in one patient, and infants born to two other patients developed purulent conjunctivitis from which H influenzae was grown. These six cases, and others from the literature, include a wide spectrum of GU tract infections due to this organism. With the rising incidence of severe infections in adults due to this organism, and the widespread emergence of ampicillin-resistant strains, H influenzae must be considered a GU tract pathogen.


Classification of lymphoma.

Classification of lymphoma. Classifications of B cell lymphomas are primarily designed for morphological diagnosis and are necessarily rigid in format, implying that clear distinctions exist between tumors composed of small lymphocytes, follicular center cells, immunoblasts, and plasma cells. This view may serve to obscure the interrelations of these neoplasms, for these cell types are not of separate lineage, but merely represent different morphological phases in the cell cycle of a single cell type--the B-lymphocyte. For lymphomas, as for neoplasia in general, the behavior of a tumor (benign vs malignant) may be predicted from the degree to which the neoplastic cells retain the function and form of the progenitor cell type. This review seeks to apply these principles to the diagnosis and classification of lymphocyte-derived neoplasms.


Brachial plexus palsy in neonates and children. In 135 children with obstetrical palsy, clinical and electrodiagnostic studies on inital and serial evaluation aided in designing a conservative treatment program. Prevention of contractures, maintenance of muscle strength and reinforcing the child's awareness of the affected limb were predicated on the limiting factors of permanent denervation and agnosia. Instability of the scapula, scapulohumeral adhesions and elbow flexion with loss of active supination defy conventional range of motion exercises. Forced passive supination of the elbow may actually compound the problem of radial head dislocation and ulnar bowing. Because of the young age of most of the patients, only 7 have had orthopedic intervention. Rotational osteotomy of the humerus and transfer of intact muscles seem to improve function. Prior to selection of muscles for transfer, electromyography is advised. Later surgical treatment of the shoulder and elbow seems to improve cosmesis but not function. Of the 135 children, 70% had mild residua, 22% showed moderate impairment and 8% had severe deficit.


Corneal endothelial dystrophy. A study of 64 families. A prospective study was undertaken during an 18-month period with 64 families who had endothelial dystrophy. Two hundred twenty-eight relatives were examined. Of those older than the age of 40, 38% were affected. Women were affected more severely and 2.5 times more frequently than men. The disease showed a strong familial tendency: there was one family in which three generations were affected and 16 families in which two generations were affected. There were four families that had members with edema in two generations. There was no association between edema in a parent and edema in a child. The proportion of relatives affected and the severity of involvement increased with age. Fifty-three probands and 18 relatives had endothelial dystrophy with edema (Fuchs' dystrophy). Of these 71, one had glaucoma.


Correlation of clinicopathologic findings in a patient. Congenital night blindness, branch retinal vein occlusion, cilioretinal artery, drusen of the optic nerve head, and intraretinal pigmented lesion. The ocular clinicopathologic features of this unique patient were congenital stationary night blindness, drusen of the optic nerve head, cilioretinal artery, intraretinal pigmented lesion, and branch retinal vein occlusion. Photocoagulation therapy led to total disappearance of the neovascular tissue, clinically and histopathologically. Histopathologic examination showed an occluded branch vein associated with a sclerotic retinal arteriole. Peripheral to the site of venous occlusion, inner ischemic retinal atrophy was present. The normal complement of rod and cone photoreceptors supports the view that the night blindness in this case was an abnormality in the neural transmission and not on a morphological basis. The pigmented intraretinal lesion proved to be a localized area of retinal and choroidal neovascularization with anastomosis and secondary retinal pigment epithelial hyperplasia. This lesion was identical to Fuchs' dot of myopia but out patient was hyperopic.


Results of aortocoronary bypass operations. Follow-up in 343 patients. Three hundred and forty-three patients who had aortocoronary bypass graft operations for disabling angina were followed up for from 6 months to 5 years (average 2 years). 80 per cent had multiple grafts and 20 per cent had additional endarterectomy. The overall mortality within one month of operation was 5 per cent, and in those who had vein graft procedures only was 4 per cent. 11 per cent had a postoperative myocardial infarction (6% perioperative) and there were 3 per cent late deaths. At 3 years 90 per cent are surviving. 80 per cent are asymptomatic without treatment. The mean angina grade was 0.3 at the latest follow-up, compared with 2.5 before operation; maximum exercise tolerance was also significantly improved (P less than 0.001). When angina recurred, it did so in 80 per cent of the cases within 12 months of operation and was usually attributable to inadequate revascularisation. Ventricular function as assessed by preoperative ventriculography was the factor most clearly related to survival rate and the early excellent results of coronary bypass operations seem to be maintained up to 5 years. It is, therefore, reasonable to continue to advise operation if only for relief of angina.


Haemodynamics during maximal exercise after coronary bypass surgery. Fifty patients underwent an objective measurement of physical working capacity by means of a multistage test of maximally tolerated exertion before and after coronary bypass surgery; 29 patients also had haemodynamic measurements during maximal exercise before and after coronary bypass surgery. The patients were divided into 3 groups according to the degree of revascularisation: adequate (n = 20), partial (n = 17), or none (n = 13). Adequate revascularisation induces a large increase in physical working capacity because of an increased maximal heart rate and maximal cardiac output; stroke volume during maximal exercise and ejection fraction at rest were not modified, suggesting no major changes in left ventricular function. After unsuccessful coronary bypass surgery, the physical working capacity was unchanged despite an increased maximal heart rate; maximal cardiac output was unchanged and stroke volume during maximal exercise was significantly lower. These undesirable results are often associated with perioperative myocardial infarction and are attended by a decreased ejection fraction at rest; these data suggest an impaired left ventricular function after unsuccessful coronary bypass surgery. The results of partial revascularisation are intermediate but appear to be determined by the incidence of partial graft failure which is also often associated with perioperative myocardial infarction. From individual changes in data collected during maximal exercise testing, it is often impossible to predict the degree of revascularisation.


Effect of prednisolone on the growth of human bone marrow cells in vitro. The addition of prednisolone to autostimulatory cultures of human bone marrow in agar results in the formation of an increased number of granulocytic aggregates. The effect is dependent on the concentration of cultured cells and does not occur at low cell concentration. The increase in aggregate numbers is maximal early in the culture and occurs at steroid concentrations which are comparable with pharmacological levels. Prednisolone directly inhibits the responsiveness of granulocytic precursors to colony-stimulating activity (CSA) and it is suggested that the stimulatory effect is indirect and may be caused by a steroid action on mediator production. These findings may be relevant to the polymorphonuclear leucocytosis induced by glucocorticoids.


Effect of experimental inflammation on the synthesis and distribution of antithrombin III and alpha1-antitrypsin in rabbits. Local inflammation, induced by s.c. injection of turpentine, evoked characteristic changes in the metabolism of antithrombin III, and alpha1-antitrypsin. For a period of approximately 36 h, the plasma half-lives of both protease inhibitors were shortened to 70--74% of the respective preinjection values. Similar changes were also observed in the slope of iodine-labelled albumin, suggesting that increased capillary permeability was primarily responsible for the losses of labelled proteins from the circulation. Incorporation of [3H]- or [14C]-leucine into albumin changed little during inflammation, but markedly increased values were measured for anti-thrombin III (3-fold), alpha1-antitrypsin (4-fold) and, above all, for fibrinogen (7-fold) 24 h and 48 h after the injection of turpentine. These changes in synthesis and elimination rates resulted in the following net balances: fibrinogen concentrations in plasma rose substantially during the early phase of inflammation; alpha1-antitrypsin concentrations increased gradually but to a significantly lesser extent, peak concentrations being reached after a reverse trend in fibrinogen concentrations had become apparent; antithrombin III concentrations remained steady throughout at levels which were only marginally above the pretreatment values.


Bilateral versus unilateral cataract extraction: advantages and complications. Cataract extraction was performed on 734 patients. These were followed up postoperatively for up to 1 year. In 448 cases the extraction was performed in both eyes during 1 operating session (896 eyes) and in 1 eye in 286 cases, a total of 1182 cataract extractions. Preoperatively more than 75% of the eyes in both groups had perception of light only. Postoperatively more than 85% of eyes in both groups achieved a visual acuity of 6/30 or better. The postoperative visual performance of an eye was not influenced by the mode of operation, bilateral or unilateral. The overall incidence of complications among the 1182 operated eyes was: accidental extra-capsular cataract extraction 10.2%, vitreous loss 11.0%, hyphaema 1.4%, flat anterior chamber 0.9%, dehiscence of the wound 0.5%, uveitis 1.2%, endophthalmitis 0.3%, secondary glaucoma 0.9%, severe bullous keratopathy 1.4%, oedema of the macula 0.5%, and retinal detachment 0.3%. The complications in both groups of patients were comparable. Only in 1 case operated in both eyes vision was not restored following a bilateral endophthalmitis.


Purification, characterization, and amino acid sequence of rat anaphylatoxin (C3a). C3a anaphylatoxin derived from the third component of complement has been isolated from rat serum and its complete amino acid seuqence determined. A three-step purification procedure was employed that consisted of gel filtration on Sephadex G-100, followed by chromatography of the anaphylatoxin-containing pool on carboxymethylcellulose. A subsequent separation on DEAE-Sephadex resolved C3a from minor contaminating peptides. Biological studies have shown that purified rat anaphylatoxin is approximately twice as active as human or porcine C3a when tested for smooth-muscle contraction. In addition to the active form of rat anaphylatoxin, a serum carboxypeptidase B inactivated form of C3a (C3ades-Arg) was purified from rat serum and utilized in subsequent structural studies. Sequence analysis of rat C3a was facilitated by a long automated Edman degradation which established the first 55 residues of the anaphylatoxin. Overlapping peptides were generated by cyanogen bromide and trypsin, and the resultant fragments were sequenced by either automated or manual Edman procedures. The primary structure of rat C3a is 70% identical to the previously determined structures of human and porcine anaphylatoxin. Antisera raised to the purified rat peptide do not cross-react immunologically by Ouchterlony analysis with either human or porcine C3a.


Effects of dehydration on reaction centers from Rhodopseudomonas sphaeroides. Air-dried films of reaction centers from Rhodopseudomonas sphaeroides were found to resemble aqueous suspensions of these reaction centers in their optical and photochemical properties, except that the long wave absorption band of bacteriochlorophyll was shifted from about 860 to 845 nm. The quantum efficiency of the photochemical reaction that produces oxidized bacteriochlorophyll and reduced ubiquinone was greater than 0.75 in the films, using 800-nm actinic light. Dehydration of the films caused further blue shifts of all the absorption bands between 500 and 900 nm, and some loss (about 20%) of intensity of the long wave band, coupled to a gain of absorbance centered at 795 nm. The latter changes were not accompanied by an increase at 1250 nm, ruling out the oxidation of bacteriochlorophyll as a cause of these changes. Dehydration caused about 50% of the reaction centers to become photochemically inactive. For the component that remained active, the photochemical quantum efficiency was about 0.5 at room temperature, rising to 0.7 or more as the temperature was brought below 250 K. The yield of 900 nm fluorescence was approximately the same in air-dried films as in aqueous suspensions; dehydration of a film raised the fluorescence yield about 3-fold. The yield of this fluorescence in a dehydrated film was independent of temperature (+/- 10%) between 300 and 70 K. The back reaction after illumination, return of electrons from reduced ubiquinone to oxidized bacteriochlorophyll, has kinetics in which a most rapid first-order component is mixed with slower components. The fastest component, identified with the return of electrons from 'primary' ubiquinone to oxidized bacteriochlorophyll, was predominant in the materials tested here. Its half time in an aqueous suspension of reaction centers fell from 86 ms at 300 K to 33 MS AT 200 K and declined more gradually to 15 ms at 50 K. An air-dried film showed similar behavior. The dramatic change of half-time between 300 and 200 K can be ascribed to one or more phase transitions involving water; in a dehydrated film the half-time of the fastest decay component was about 22 +/- 5 ms, independent of the temperature between 300 and 70 K. The original properties of an air-dried film were restored fully, after dehydration, by exposure to either H2O or 2H2O vapor. There was no significant difference, in these measurements, between H2O-restored and 2H2O-restored films.


Non-step intracellular voltage response of epithelial and oxyntic cells in frog gastric mucosa. Intracellular analyses of the electrical potential response to current pulses were performed in epithelial and oxyntic cells of the frog gastric mucosa. Independently of the use of Cl- or SO(2-)4 solutions and of the transmucosal potential difference measured, the resistance and slow potential changes observed across the mucosal surface of epithelial cells are not different from those registered across the serosal surface. In the oxyntic cells the resistance and slow potential changes are significantly higher across the mucosal than across the  serosal surface, when the solution in contact with the serosal surface is positive with respect to the solution in contact with the mucosal surface. These differences were not observed when the transmucosal potential difference was reversed. It is proposed that the ionic concentration changes, by effect of current flow across the mucosa, occur in the oxyntic cells and that these changes are the origin of the slow transmucosal potential change. The epithelial cells act as a passive shunt.


Substrate specificity and other properties of DOPA decarboxylase from guinea pig kidneys. DOPA decarboxylase (aromatic-l-amino-acid carboxy-lyase, EC 4.1.1.28) from guinea pig kidneys has been purified to a specific activity of 9370 or 330-fold. Efficient purification was possible by employing apolar interaction chromatography. The purified enzyme gives a single component on polyacrylamide gel electrophoresis and the absorption spectrum of the enzyme reveals two forms of binding of pyridoxal 5-phosphate. The pure enzyme decarboxylates l-DOPA, 5-hydroxytryptophan, o-tyrosine and m-tyrosine but it is inactive towards phenylalanine, tyrosine, tryptophan, histidine and 3-methoxy-phenylalanine. The enzyme behaves as an undissociated enzyme but only towards 5-hydroxytryptophan. It behaves as an enzyme from which the coenzyme is partially dissociated when it attacks l-DOPA, o-tyrosine and m-tyrosine.


omega- and (omega--1)-hydroxylation of fatty acids by frog liver microsomes. Substrate specificity and other properties. Frog liver microsomes catalyzed the hydroxylation of various saturated fatty acids whose chain lengths were from 8 to 18 carbon atoms into the corresponding omega- and (omega--1)-hydroxy derivatives. In addition, small amounts of the dicarboxylic acids and (omega--1)-keto acids were also formed from all the fatty acids. The relative activity of the hydroxylase with the substrates was as follows: C13(100), C12(98), C14(88), C10(62), C16(34), C18(29), and C8(8). The percentage of omega-hydroxy derivative relative to the (omega--1)-isomer increased with increasing carbon chain length of the fatty acid substrate. Oleate, linoleate and linolenate were also tested and found to be at least as active their saturated analog (stearate). Both NADPH and O2 were required for hydroxylase activity. The apparent Km for NADPH was 3.7 . 10(-5) M, and NADH had very little effect. The apparent Km value for laurate was 1.5 . 10(-5) M. The hydroxylating system was about 50% inhibited by 10 mM KCN and 81% inhibited by CO at a CO : O2 ratio of 4.0. In contrast, NaN3 showed no effect on hydroxylation.


Stimulation of platelet production in vivo by a factor in cell culture conditioned medium. Injection of medium conditioned by a murine myelomonocytic leukaemic cell-line (WEHI-CM) stimulates platelet production in irradiated, bone marrow reconstituted mice. Media conditioned by the growth of normal bone marrow cells (BM-CM) or by a lymphoid leukaemia cell line had no effect on platelet production. However, the effect of WEHI-CM on platelet production was further enhanced when injected along with BM-CM, indicating that more than one factor may play a role in the regulation of megakaryocytopoiesis.


[Role of cholinergic and serotoninergic processes in modulating the activity of the negative reinforcement system]. The influence of choline- and serotoninergic drugs upon the latency of switching off the central aversive stimulation was investigated. Physostigmine and fluoxetine were shown to increase the latency of escape. Scopolamine and p-chloroamphetamine could both increase the time of active escape and decrease it. Fluoxetine diminished the activation effect and inversed the inhibitory effect of scopolamine. Fluoxetine potentiated the inhibitory action of physostigmine. p-Chloroamphetamine attenuated the inhibitory effect of physostigmine and increased scopolamine effect. It is suggested that choline- and serotoninergic mechanisms depressed the activity of the negative reinforcement system. Functional interaction is postulated between these neuromediator systems.


[Supressor activity of spleen cells during medically induced immunologic tolerance]. SRBC tolerance was induced in mice (CBA X C57BL/6) F1 by single intraperitoneal injection of 6 X 10(9) SRBC and of cyclophosphamide (100-200 mg/kg) in 44-46 hours. Spleen cells of tolerant mice obtained at various periods after the tolerance induction (in 12-26 days) failed to decrease their immune response to SRBC after administration to intact syngeneic recipients. Contrary to intact mice, tolerant animals were incapable of producing suppressor cells after a single SRBC immunization. Only when 3 additional injections of high SRBC doses (6 X 10(9)) were given to tolerant mice the spleen cells in them acquired the capacity to inhibit the immune response after administration to normal mice. It is supposed that the absence of suppressor cells in induction of the immunological tolerance by means of cyclophosphane was caused by the processes of clone elimination. Suppressor cells can originate in tolerant animals under the effect of intensive antigenic stimulation, this leading to enhancement of the tolerance state as a result of additional SRBC injections.


Monoamine metabolism during bicuculline-induced epileptic seizures in the rat. Brain levels of tyrosine, dopamine (DA), noradrenaline (NA), tryptophan, 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were measured after 30, 60 and 120 min of sustained seizure activity, induced in paralyzed, artificially ventilated and anaesthetized (70% N2O) rats by administration of bicuculline (1.2 mg/kg i.v.). In separate animals the rates of accumulation of DOPA and 5-hydroxytryptophan (5-HTP) were estimated in three different brain regions after blockage of the aromatic L-amino acid decarboxylase with NSD 1015 (100 mg/kg). The tissue level of NA was markedly reduced at 30 min and remained low during 120 min of sustained epileptic seizures. In contrast, the DA concentration, being essentially unaffected at 30 min, continuously increased during the following 90 min. 5-HT decreased significantly after 30 min but returned to control levels following 60 and 120 min of seizure activity. The 5-HIAA concentration progressively increased. In all three brain regions (striatum, limbic forebrain and hemispheres) the rate of tyrosine hydroxylation increased. Tryptophan hydroxylation showed a significant increase only in the limbic forebrain. The results suggest that bicuculline-induced seizures lead to an increased functional activity in NA neurons and, at least initially, also in 5-HT neurons. In contrast, DA neurons appear to be inhibited.


Influence of transient ischemia on monoamine metabolism in the rat brain during nitrous oxide and phenobarbitone anaesthesia. Cerebral ischemia was induced in normothermic, artificially ventilated rats, anesthetized with 70% N2O or 150 mg/kg of phenobarbitone, by bilateral occlusion of the common carotid arteries and by simultaneous depression of the mean arterial blood pressure to 50 mm Hg. The levels of tyrosine, dopamine (DA), noradrenaline (NA), tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were measured after 15 min of ischemia as well as after 30 min of recirculation. In separate experiments (70% N2O) the rate of accumulation of DOPA and 5-hydroxytryptophan (5-HTP) was determined in three different brain regions (striatum, limbic forebrain and hemispheres) during recirculation. During ischemia, the monoamine pattern was unaffected. Following recirculation, increases in DA, 5-HIAA, tyrosine and tryptophan were found irrespective of the type of anesthesia used. Pronounced postischemic decreases in NA and 5-HT were observed in animals anesthetized with nitrous oxide but not in those given phenobarbitone. During recirculation the rate of tyrosine hydroxylation increased in all three brain regions while tryptophan hydroxylation was reduced. It is tentatively concluded that following transient, global cerebral ischemia, neuronal activity is low or eliminated in dopaminergic and serotoninergic neurons and high in noradrenergic neurons.


Massive lower gastrointestinal bleeding: an unusual complication of Crohn's disease. Massive rectal bleeding may complicate Crohn's disease at any stage and tends to be persistent. Limited experience gained with this complication supports the use of selective agiography followed by conservative resection as the management of choice. Results of experimental studies suggest that selective infusion of vasopressors may be safely attempted when hemorrhage complicates Crohn's disease in its early stages but is probably too hazardous in cases in which the disease is more advanced.


Comparison of the effects of single versus multiple agent chemotherapy on lymphocytes assayed by the rosette technique. The percentage of peripheral blood Total T, Active T and B-Rosette Forming Cells (RFC) were determined serially (Day 0, 1, 2, 7, and 21) following administration of single (SAT) versus multiple (MAT) agent chemotherapy. SAT caused essentially a decrease in the percentage of B-RFC. MAT resulted in profound decrease of Active T and B-RFC and to a lesser degree of Total T-RFC percentages with nadirs being reached in 48 hours. The most striking decrease involved the percentage of Active T-RFC which remained 15% below pretreatment level 7th posttreatment day. The posttreatment changes in the absolute numbers of Total T, Active T and B-RFCs following MAT were similar to that noted on the RFC percentage. Effects of the two most commonly used multiple agent treatments (COBAM and DOMF) were comparable. MAT causes a more profound decrease in the percentage of various RFCs than SAT. The differences between the nadirs of various RFC reached Day 1 and 2 with MAT versus SAT are statistically significant (p less than .001). We conclude that the effects of chemotherapy on peripheral RFC may be best evidenced by serial determination of their percentage rather than their absolute numbers. Subpopulation of the T-RFC which has been labeled Active T-RFC appears to be the best indicator of the chemotherapy effects on the lymphocyte population since they demonstrate the most profound and persistent changes.


Dynamic parameters of membrane lipids in normal and leukemic human lymphocytes isolated from peripheral blood and bone marrow. The degree of microviscosity (eta), and lipid fluidity (LFU) of cellular membranes of normal and leukemic lymphocytes obtained from peripheral blood and bone marrow of normal donors and acute lymphatic leukemic (ALL) patients was quantitatively monitored by fluorescence polarization analysis with the aid of the fluorescent lipophilic probe 1,6-diphenyl-1,3,5-hexatriene when embedded in cellular membranes of intact cells. The results have shown a marked decrease in eta and a significant increase in LFU in lymphocytes obtained from both peripheral blood and bone marrow of ALL patients at admission when compared to both T- and B-lymphocytes obtained from peripheral blood of normal donors. Moreover, both dynamic parameters, eta and LFU, show normal characteristic values in lymphocytes obtained from bone marrow of ALL patients in complete hematological remission. Since in few cases a decrease in eta and an increase in LFU were observed in bone marrow lymphocytes isolated from ALL patients in remission, the possibility that these dynamic parameters may serve as a diagnostic tool for an early detection of a new relapse is discussed.


Extravascular transfer within the anuran pars intermedia. To study the transport of protein from the blood into and throughout the sparsely vascularized pars intermedia of anurans, the electrondense tracer, horseradish peroxidase (HRP) was injected into the vascular system of adult frogs. A strong reaction product was localized in small vesicles in the cytoplasm of that portion of the stellate cells immediately beneath the vascular spaces. Also, within two minutes after an injection of HRP, which was given during a period of one minute, the reaction product was seen in the extracellular spaces between the stellate and/or MSH secretory cells throughout the gland. Additionally, it appeared that HRP was pinocytosed by the stellate cell processes in the interior of the pars intermedia. Since frogs adapted to different backgrounds were perfused with HRP for a variety of time periods, from 3 to 90 min, it was thought that it would be possible to trace the pathway of the HRP-filled vesicles as they moved through the stellate cells. There did not appear to be a migration of these vesicles within the cells. Because of the electron density of the HRP, the tortuous extensions from the perivascular spaces of the capillary plexus intermedius were obvious as they ramified into the pars intermedia and pars nervosa. In the frogs not injected with HRP, it was possible to observe the substructure of these ramifications which paralleled the stellate cells and formed enlargements at the convergence of the stellate cell processes and sometimes the nerve processes. An extravascular, many-branched transport system that penetrates the parenchyma is discussed in addition to the possible transfer role of the stellate cells.