[Trisomy 11q. Individualization of a new syndrome]. The comparison of nine examples of trisomy for the distal segment of 11q permits definition of a clinical syndrome which includes the following: axial hypotonia with hypertonia of the limbs; an old-looking wrinkled face; a large beaked nose; microretrognathia with malformation of the palate; low-set ears; a prominent anterior helix; a prominent anthelix; a short neck; a narrow chest with nipples set widely apart; micropenis in the boys; congenital heart disease; renal agenesis or malformations of the urinary tract; agenesis of the thoracic girdle; dysplasia of the acetabulum; clubfeet.


Human acrocentric ring chromosomes and satellite association. In four cases of human acrocentric ring chromosomes r(21)(p13q22); r(21)(p11q22); r(13)(p11q?); and R(21)(P11Q22), association of the annular with normal D and G chromosomes was found. This finding indicates that: 1) the "satellite" association is not terminal 2) the heterochromatic region (band p11) adjacent to the acrocentric short arm constriction contains nucleolar organizers (NOs), although bands p12 and 13 could not be excluded; and 3) band p11 probably has two different functional sites, a distal NO+ and a proximal NO-. Related studies on three C/G translocation carriers suggest a non-specific interphase interchromosomal relationship.


[Trial of detection of female carriers for the ornithine-carbamyltransferase deficiency by the urine assay of crotic acid. Apropos of a family study]. Studies on the detection of female carriers of the gene responsible for ornithine carbamoyl transferase deficiency are reported. The method used was that described by Goldstein and is based on provoked acidemia after an oral protein overload. Transmission of the disease as a sex linked dominant was confirmed. The heterogeneity of the metabolic disorder is discussed.


Milk casein polymorphism in the Kikuyu population. Urea-starch-gel electrophoresis of casein samples from women of the Kikuyu tribe (central Africa) shows that this Negroid population had the same alpha- and beta-casein polymorphic pattern as Caucasoids, though their gene frequencies for the beta-locus were inverted. A new beta-casein variant (named beta-E) was identified.


Report of a case of 46,xx/45,xx,-20 mosaicism. A 46,XX/45,XX,-20 mosaicism was observed in a phenotypically normal female who had three grossly malformed children (two stillbirths and a perinatal death).


Study of two acetylcholine analogs with fixed conformations. Two acetylcholine analogs, compound M (4,4-dimethyl-2-morpholonium) and compound P (1,1-dimethyl-3-acetoxypiperidinium) which contain the N-C-C-O group of acetylcholine fixed in the gauche and trans conformations, respectively, were tested for activity on the terminal ileum of the rat, the rectus abdominis muscle of the frog, and the superior cervical ganglion of the cat. It was found that compound M stimulates the ganglion but has no affinity for receptors in either the ileum or the rectus muscle, while compound P stimulates cholinergic receptors in the ileum and in the fast fibers of the rectus muscle but acts neither on the slow fibers of the rectus muscle nor on the ganglion.


Histological observations of inhibitory effect of testosterone on lymphoid regeneration in the thymus-independent areas of B mice. High doses of testosterone were subcutaneously given to B mice, neonatally thymectomized, lethally irradiated and reconstituted with syngeneic bone marrow cells. Histological observations of the peripheral lymphoid tissues revealed that testosterone inhibited the regeneration of the thymus-independent areas which were considered to be composed mainly of B lymphocytes. This result suggests that testosterone would inhibit the differentiation of B lymphocytes.


[Bone dysplasia with dwarfism and diffuse skeletal alterations]. Six cases of a new hereditary chondrodyplasia are reported. The features are severe dwarfism, generalized hypotonia, frequent and considerable desaxations of fingers and toes. Slight facial dysmorphism with evolutive scoliosis is often associated. Osteopetrosis is diffuse and is associated with important metaphyseal widening as well as epiphyseal irregularities and often carpal and tarsal supernumerary bones. No metabolic or chromosomal abnormality was found. The relations of the disease with related types described in Larsen's syndrome are considered.


Ocular manifestations of hypercupremia associated with multiple myeloma. Extensive copper infiltration of Descemet membrane of the central cornea and of the anterior and posterior surfaces of the lens is associated with marked hypercupremia related to an abnormal immunoglobulin. Observation of this spectrum of ophthalmic changes in an apparently well middle-aged woman heralded the diagnosis of a unique variety of multiple myeloma.


Haemobilia from pancreatic cystadenoma.

Haemobilia from pancreatic cystadenoma. Hamobilia from a pancreatic source is a rare cause of gastrointestinal haemorrhage. Most of the reported cases have arisen from haemorrhage into a pancreatic pseudocyst, which is frequently fatal. This report describes a patient with gastrointestinal haemorrhage arising from a pancreatic cystadenoma.


Control of 5-aminolaevulinate synthetase activity in Rhodopseudomonas spheroides a role for trisulphides. 1. The aminolaevulinate synthetase activator of fresh extracts of semi-anaerobically grown Rhodopseudomonas spheroids was resolved into two fractions by ion-exchange chromatography. One fraction was identified as cystine trisulphide (CySSSCy). Analysis of the other fraction indicated the presence of about equal amounts of glutathione trisulphide (GSSSG) and the mixed trisulphide of glutathione and cystine (GSSSCy). 2. Four further fractions with activator activity were observed on ion-exchange chromatography of extracts prepared by methods similar to those described earlier [Neuberger et al. (1973)Biochem. J. 136,491-499]. These activators were generated by the extraction procedure. Two of them have been identified as trisulphanedisulphonate (S5O62-) and additional cystine trisulphide. 3. For the series of polysulphanedisulphonates (-O3S-Sn-SO3-, n greater than or equal to 1), activator activity at muM concentrations was exhibited only by compounds with n greater than 3. This, together with the results described above, indicates that for a compound R-Sn-R' (where R and R' are organic or inorganic groups) the only structural requirement for activity is n greater than or equal to 3. 4. Oxygenation of a semipanaerobic culture of R. spheroids for 1.5h before harvesting the cells produced a decrease of more than 90% in the cellular content of cystine trisulphide and glutathione trisulphides. 5. Chromatography on DEAE-Sephadex confirmed the presence of multiple forms of aminolaevulinate synthetase in extracts of R. spheroides [Tuboi et al. (1970) Arch.Biochem. Biophys. 138,147-154]. Oxygenation of a semi-anaerobic culture resulted in the disappearance of high-activity enzyme (a-form) and the accumulation of low-activity enzyme (b-form) in the cell. Spontaneous activation [Marriott et al. (1969) Biochem. J. 111,385-394] And activation by cystine trisulphide both resulted in the almost complete conversion of the b-form into the a-form.


Membrane receptor sites for the identification of lymphoreticular cells in benign and malignant conditions. The cells of the lymphoreticular system are heterogeneous both morphologically and functionally. The bone marrow derived (B) lymphocyte can be identified by the presence of easily detectable surface immunoglobulin and a receptor for antigen-antibody-complement (EAC) complexes. Monocytes and histiocytes also bear a receptor for EAC and in addition possess a receptor for cytophilic antibody detected with red cell--IgG complexes (IgGEA). In man, thymus derived (T) lymphocytes form non-immune rosettes with sheep red blood cells (E). We have examined a number of malignant lymphoreticular populations for the presence of the EAC, EA, and E receptors on suspensions of cells and have adapted the technique to demonstrate the EAC and EA receptors on  frozen tissue sections. Rosetted malignant cells can also be cytologically examined on Millipore filters. The malignant cells both in section and suspension from the spleens and lymph nodes of 6 patients with nodular lymphoma bound EAC but not IgGEA or E; by these criteria these malignant cells are of B lymphocytic origin. The malignant cells from the spleens of 2 patients with leukaemic reticuloendotheliosis and 1 patient with malignant histiocytosis could be classified as being of histiocytic origin by the selective binding of IgGEA. In 3 cases of diffuse lymphocytic lymphoma the malignant cells bound only E and are therefore of T lymphocytic origin. The application of these techniques to the classification of malignant lymphoma may lead to important theoretical and therapeutic advances.


Evaluation of T and B lymphocyte membrane markers in human non-Hodgkin malignant lymphomata. Lymphoma cells from 25 patients were studied for the presence of B lymphocytes (membrane bound Ig and Fc receptor) and T lymphocytes (rosette formation with sheep erythrocytes) membrane markers. All cases of well differentiated lymphocytic lymphoma and of acute lymphosarcoma cell leukaemia and most cases of poorly differentiated lymphocytic lymphoma behaved as B cell monoclonal malignancies. However, the malignant cells of some patients were not definitely classified according to their B or T cell origin or lacked these membrane markers. The latter situation was encountered in 4 reticulum cell sarcomata. Polyclonal Ig were found on the surface of B cells in a case of hyperbasophilic undifferentiated lymphoma. The need for using several membrane markers to study the abnormal lymphoma cells is outlined. Such studies improve our understanding of these malignancies and may lead in the future to a satisfactory classification of non-Hodgkin lymphomata.


Action of aldosterone on frog skin in the presence and absence of in vitro molting effects. The molting which occurs in frog skin following exposure to high concentrations of aldosterone interferes with the interpretation of physiological measurements. Exposure of skins from frogs maintained in standard smooth tanks to 5 - 10(-7) M aldosterone caused within a few hours erratic responses in short-circuit current Io and conductance K followed by sustained stimulation of Io and K; 10(-8) M aldosterone caused only stimulation of Io and K. Storage of frogs in "rojgh tanks" eliminated in vitro molting on exposure to 5 - 10(-7) M aldosterone. IO and K were then superimposable for 3 h, after which Io increased far more rapidly than K. These results are consistent with an early effect on permeability of the active pathway and later effects on metabolism, either a direct effect on the pump or enhanced interaction between transport and metabolism.


A rapid method for purification of human granulocyte cationic neutral proteases: purification and characterization of human granulocyte chymotrypsin-like enzyme. A chymotrypsin-like enzyme (EC 3.4.21.-) was purified from granules of human neutrophiles (polymorphonuclear leucocytes). The isolation procedure included differential salt extractions of the granules followed by affinity chromatography on 4-phenylbutylamine-Affi-Gel. This rapid purification method resulted in obtaining pure enzyme in relatively high yield in short time. The purified granulocyte chymotrypsin-like enzyme has a minimum Mr of 22 378, calculated from its amino acid composition. The Mr value obtained by sodium dodecyl sulphate gel electrophoresis was 20 000-23 000. The enzyme did not react with antibodies which are monospecific to granulocyte elastase. The granulocyte chymotrypsin-like enzyme was inactivated by Dip-F and by the chloromethyl ketone derivatives Z-PheCH2Cl and Z-(Gly)2-PheCH2Cl but not by Tos-PheCH2Cl. It therefore appears that the enzyme has serine and histidine side chains in its active site, like pancreatic chymotrypsin. The granulocyte enzyme substrate specificity is similar to that of pac-Tyr-Nan and Ac-Phe-1-ONap. It also has an intrinsic weak hydrolytic activity towards some classical elastase substrates such as Boc-Ala-ONp and Ac-DL-Ala-1-ONap. The granulocyte enzyme is inhibited by human serum and by human alpha1-antitrypsin. Its affinity for alpha1-antitrypsin is weaker than that of granulocyte elastase for the same inhibitor. The enzyme is stable at neutral pH at 37 degrees C, but unstable at pH 3.5 and at elevated temperature.


Structure and active transport in the plasma membrane of the tubules of frog kidney. The active transport of organic anions through the plasma membrane of the proximal tubules of frog kidney was studied. For this purpose a marker anion, fluorescein, was used, its flow into the tubules registered by the increase of fluorescense. The kinetics of transport was measured as function of time, concentration of substrate, concentration of a competing acid (p-aminohippuric acid) and temperature. The process is inhibited by strophantin, a specific poison for (Na++K+)-dependent ATPase. These data show that fluorescein transport is effected with the participation of a charged carrier, probably by the downfield mechanism postulated by Mitchell. To confirm this mechanism, a passive flow of K+ was created inwards across the membrane of the proximal tubules by means of valinomycin. It led to the discharge of the membrane and to the inhibition of fluorescein transport. Anions are transported downfield across the membrane, probably in a state of complexes with two Na+ ions. A magnetic field of 10000-28000 oersted inhibits the fluorescein transport strongly. This can be regarded as a proof of the liquid-crystalline structure of biological membranes and demonstrates the importance of this structure for active transport.


Alpha1-antitrypsin concentration in amniotic fluid. Concentrations of alpha1-antitrypsin were measured in 80 specimens of amniotic fluid collected at various stages of pregnancy. Levels remained relatively unchanged throughout gestation, with a median concentration of 10.0 mg/100 ml at 12-24 weeks, 18.7 mg/100 ml at 34-37 weeks, and 16.2 mg/100 ml, after the 37th week. In three instances where the infant developed RDS, the median concentration was 12.4 mg/100 ml.


Radiology in the diagnosis of colloid cysts of the third ventricle. A series of 38 cases of colloid cyst of the 3rd ventricle is described in most of whom the diagnosis, important for curative surgery, was made radiologically. The most useful investigative technique was pneumography, by which the tumour was outlined in almost all cases. The lateral "hanging head" projection generally demonstrated the lesion most satisfactorily. Care in manipulating air introduced at ventriculography through the foramina of Monro into the 3rd ventricle was frequently rewarded by clear definition of the tumour. In more than one-third of the cases, the lateral plain skull radiograph showed truncation of the dorsum sellae indicative of chronic obstructive hydrocephalus, and, in the large majority of these, pneumography confirmed that the 3rd ventricle, rather than the interventricular foramen, was the site of obstruction to the drainage of cerebrospinal fluid. Carotid angiography, showing hydrocephalus, and in the same cases elevation and lateral displacement of the anterior portion of the internal cerebral veins yielded strong supportive evidence. Vertebral angiography was less specific, and isotope scanning was quite unhelpful.


Trigger factors and HL-A antigens in chronic active hepatitis. Forty-six patients with histologically verified chronic active hepatitis (CAH) were divided into three groups according to whether the CAH was virus-induced, drug-induced, or cryptogenic. The frequency of the HL-A antigens 1 and 8 was increased in the cryptogenic group while the other groups did not differ significantly from healthy controls. Autoantibodies were often found in high titres in the drug-induced and cryptogenic groups but were infrequent in the virus-induced group.


Spatial and temporal organization of the binocular input to frog optic tectum. Single-unit recordings in the frog's optic tectum have demonstrated the existence of a systematic spatial separation between the direct contralateral and indirect ipsilateral excitatory receptive fields. Marked differences in this spatial organization were found between paralyzed and anesthesized animals. Significant latency differences were found between sustained (class I/II) and transient (class III) contralateral fibers. Corresponding latency differences were also seen in ipsilaterally driven responses. It is suggested that there may be at least two different classes of ipsilateral fibers. The existence of binocular interaction at the level of the afferent terminal arborizations was investigated, utilizing temporally asynchronous dichoptic stimulation. No such phenomena were seen in curarized animals. These findings are discussed in terms of possible velocity and direction sensitivity mechanisms.


Significance of new Q waves after aortocoronary bypass surgery. Correlation with changes in ventricular wall motion. From June 1969 to December 1974, 142 patients underwent aortocoronary bypass surgery at the Veterans Administration Hospital, San Francisco. Seventeen patients developed new Q waves; two of four deaths in the hospital occurred among these 17 patients. Preoperative and postoperative catheterization data were available for analysis in 12 of the 15 surviving patients. Longitudinal, transverse, and hemiaxial segmental analysis of preoperative and postoperative single plane, 30 degrees right anterior oblique left ventriculograms revealed deterioration in wall motion in all 12 patients. The deterioration corresponded to the area on the electrocardiogram where the new Q waves appeared. In ten of 12 patients, ejection fraction also deteriorated. Twenty-six of 29 grafts were patent. New Q waves after aortocoronary bypass surgery correlate well with the appearance of localized abnormalities in wall motion. We found no evidence that perioperative appearance of Q waves was not due to new perioperative myocardial infarction.


Plasma and atrial propranolol after preoperative withdrawal. Of 34 patients scheduled for aortocoronary bypass operations who were withdrawn from chronic propranolol therapy between 18 and 48 hours before anesthesia and operation, propranolol was detected in the plasma of nine and in atrial tissue of five patients. Higher plasma levels were associated with higher propranolol intake and with shorter time of withdrawal. In 15 patients withdrawn preoperatively from propranolol the heart rate and blood pressure response to 3 mug isoproterenol was not significantly different from the response of similar patients who had received no propranolol. In contrast to the response of healthy subjects, most patients with coronary artery disease responded to isoproterenol with a decrease in systolic blood pressure. Plasma propranolol levels after a 0.5 mg bolus given intravenously during operation produced a peak level of 40 ng/ml in one minute and disappeared in five minutes. These studies suggest that no beta blockade persists 18 hours after acute preoperative withdrawal of propranolol in patients taking up to 300 mg per day for control of angina. In view of the reported hazards of abrupt withdrawal of propranolol before operation and the reported usefulness of propranolol in treating tachyarrhythmias during operation, we suggest that early preoperative withdrawal of propranolol may be more hazardous than its continuation before coronary bypass operations.


Screening for cystic fibrosis by analysis of meconium for albumin and protease inhibitors. A qualitative method of detecting elevated meconium protein concentration was compared with a method of determining meconium albumin concentration by electroimmunoassay since elevated meconium protein levels can indicate pancreatic insufficiency caused by cystic fibrosis. Between 5 and 10 per 1000 healthy infants passed meconium specimens that gave a false positive reaction with the Boehringer Mannheim test strip and contained a greater than expected concentration of albumin.  It was possible to exclude pancreatic insufficiency in all of these children by determining the ratio, albumin : alpha1-antitrypsin in meconium and subsequent faecal specimens, since it was found that values of this ratio in excess of 2.0 suggested pancreatic insufficiency of the type associated with cystic fibrosis. Three of 14 neonates with subsequently proven cystic fibrosis yielded meconium specimens giving negative test strip results and low albumin concentrations. In two of these patients, the ratio, albumin : alpha1-antitrypsin in the meconium was within normal limits but, within two months of birth, the albumin : alpha1-antitrypsin ratio in the faeces of both children was greater than 3.0 suggesting that pancreatic insufficiency had developed.


The potentiating, mitogenic and inhibitory effects on lymphocytes in vitro, of macrophages in the lymph nodes of mice 'overloaded' with mycobacterial products. The lymph nodes of mice overloaded with mycobacterial products, either by the injection of whole or ultrasonicated organisms, or as a consequence of severe infection with Mycobacterium ulcerans, contain phagocytic cells which cause spontaneous transformation of the lymph node cells in a low volume, high cell density culture system. This spontaneous mitosis is unaffected by trypsinization but is inhibited by specific antigen and by PHA, and eliminated by treatment with carbonyl iron. Replacement of the macrophages removed with carbonyl iron by a critical number of peritoneal cells, restores the spontaneous transformation. Normal lymph node, thymus or peritoneal lymphocytes will also undergo mitosis if small numbers of peritoneal cells are added to them. This phenomenon therefore appears not to be antigen-dependent, but is probably due to a mediator released from macrophages. The possible role of this phenomenon in the pathogenesis of mycobacterial disease and the 'overloading' of T lymphocytes in vivo is discussed, with reference to similar macrophage-dependent mechanisms reported in other systems.


Immunodeficiency diseases. I. T-lymphocyte precursors and T-lymphocyte differentiation in partial Di George syndrome. Immunological and pathological studies in a case of partial Di George syndrome revealed an absence of parathyroids, a major hypoplasia of thymus but a relatively moderate decrease in peripheral T-lymphocyte numbers and functions. After in vitro incubation with normal thymus extracts, a normal proportion of bone marrow cells was induced to differentiate into cells with characteristics of T lymphocytes, thus establishing the presence of T-cell precursors in the patient's bone marrow.


Increased proliferation of T lymphocytes in the blood of patients with Hodgkin's disease. We investigated the number of DNA-synthesizing T lymphocytes in the blood of patients with Hodgkin's disease, with infectious mononucleosis and in normal controls. T cells were characterized by their ability to form rosettes with unsensitized neuramidase-treated sheep red blood cells. Cells in DNA synthesis were evaluated autoradiographically after in vitro incubation with [3H]thymidine. Our results indicated a preferential proliferation of T lymphocytes in the blood of patients with Hodgkin's disease and infectious mononucleosis and suggested an increased turnover of these cells.


Myasthenia gravis: studies on HL-A antigens and lymphocyte subpopulations in patients with myasthenia gravis. Thirth-three patient with a clinical diagnosis of myasthenia gravis were tissue-typed for HL-A antigens. In agreement with earlier reports a significant increase in antigens HL-A1 and HL-A8 were found in this material. Two of the patients were treated with chronic thoracic duct drainage. Proportions of T and B lymphocytes in lymph and peripheral blood were estimated in these patients. In the lymph an initial decrease in the proportion of T cells occurred, which was accompanied by a subsequent increase in the proportion of B cells. Towards the end of the chronic drainage period this effect was reversed. A slightly different picture occurred in blood lymphocytes. Initially, there was an increase in both T and B cells, followed by a decrease in T-cells numbers in one patient, whereas in the second patient the proportion of T cells decreased from the onset of drainage while the proportion of B cells steadily increased. These studies showed that available markers for determination of T ANd B cells were useful for studies of lymphocyte subpopulations in blood and lymph. Lmyphocytes from the thoracic duct were also tested for their reactivity to various mitogens specific for either T or B cells. The B-cell mitogens which were used were dextran sulphate, lipopolysaccharide, purified protein derivative, as well as rabbit anti-human beta2-microglobulin serum. The T-cell mitogens investigated were concanavalin A and phytohaemagglutinin. No significant differences in the responsiveness of thoracic duct lymphocytes compared to normal peripheral blood lymphocytes were found.


Studies on the cytotoxic effect of in vivo and in vitro immunized lymphocytes on liver target cells. Lymph node and spleen cells from mice immunized in vivo to allogeneic of syngeneic liver antigen are cytotoxic for syngeneic liver cells, but not for syngeneic fibroblasts or established liver cell cultures of allogeneic origin. The cytotoxic activity is mainly dependent on T-cell activity, but a non-T-cell-mediated cytotoxicity may also play a role. Lymphocytotoxicity is inhibited by preincubation of the lymphocytes with syngeneic liver antigen, but not with syngeneic kidney homogenate. The liver-specific lymphocytotoxicity corresponds to the in vivo function of lymphocytes in the development of experimental hepatitis. In vitro immunization of lymphocytes in a Mishell-Dutton culture system also induces liver-specific cytotoxicity. The results indicate that the natural tolerance to self antigens can be lost after invivo as well as in vitro immunization. The induction of self-reactivity of lymphocytes in these experiments may be attributed to regulatory mechanisms of the immune reaction at a cellular level.


T and B origin of human lymphocytic leukaemia. A new immunological classification of leukaemia diseases in man was assessed by using electrophoretic mobility as a cell-marker. It was found that all acute lymphocytic leukaemia analysed in childhood were T-cell leukaemia, and the majority of chronic lymphocytic leukaemia in adults were also T-cell leukaemia. The remainder, chronic lymphocytic leukaemia in adults, were B-cell leukaemia. The above statements are only partially compatible with the classification given by the most commonly used T- and B-cell markers such as rosette formation or cell-surface immunoglobulins.


The so-called Dandy-Walker syndrome: analysis of 12 operated cases. Twelve patients between the years of 1964 and 1971 underwent surgical treatment for the so-called Dandy-Walker syndrome at the Johns Hopkins Hospital. Five patients belonged to an early group (1-8 weeks); four patients to an intermediary group (3-20 months); and a late group consisted of three patients (3 years, 14 years and 34 years). The value of the various diagnostic studies is discussed on the basis of an analysis of the plain skull X-rays, cerebral angiograms, and combined air studies. The importance of a careful delineation of the underlying pathological condition is stressed to enable the surgeon to choose the appropriate technique. The diagnostic studies confirmed the diagnosis of a true Dandy-Walker syndrome in six of the twelve cases. The remaining six proved to have either an independent posterior fossa cyst with communication of the subarachnoid space and occasionally with the ventricles; or an isolated posterior fossa cyst with no communication but with impingement on the aqueduct and on the midline structures. In six patients, a primary simple shunt procedure was performed which had to be followed by a posterior fossa craniectomy in one and by a double-shunt (ventricle and posterior fossa cyst) in another. Four patients underwent a posterior fossa craniectomy; as the primary and only procedure (2), craniectomy followed by a ventriculoperitoneal shunt (1), or an unsuccessful shunt followed by craniectomy (1). In two patients, a so-called 'double shunt' was performed as a second operation, draining simultaneously the right lateral ventricle and the posterior fossa cyst. There was no death in this series. Three children had evidence of infected shunts; they responded to adequate therapy. Four had excellent results, with normal neurological examination and normal development. Four had good results, performing in school (working) was markedly improved; two had fair results with residual neurological deficit and some mental retardation. Two patients had to be considered as poor results. Both of them, however, have shown evidence of concomitant severe congenital abnormalities of the cerebellum on the diagnostic studies. The follow-up period ranged from 1 1/2 to 7 1/2 years.


Diagnosis and surgical treatment of choroid plexus papillomas. This is a report of 22 cases of papillomas of the choroid plexus diagnosed and managed personally by the author. The angiographic diagnosis and extension of choroid plexus papillomas are described, as is the surgical technique for removing these tumors from the lateral, third, and fourth ventricles. Specific attention is given to using the angiogram as the study of choice upon which surgical technique is planned. The diagnosis of choroid plexus papilloma of the lateral ventricle is made by observing the presence of a hypertrophied anterior choroidal artery, a 'double tumor' sign with one tumor at the trigone and the other within the temporal or frontal horn, tumor stain at the trigone, and asymmetrical hydrocephalus, generally, with a shift away from the side of the larger ventricle. Posterior fossa papillomas cause symmetrical hydrocephalus and generally have tumor stain located within the midline, with the major feeding coming from either the superior cerebellar or the posteroinferior cerebellar arteries. Surgical removal of the tumor should entail an 'en bloc' resection following occlusion of the feeding and draining vessels. The tumor should be removed directly when it is in the lateral ventricle and following ventriculocerebral spinal fluid shunting when it is in the posterior fossa.


[Clinical experiences with dopamine after heart surgery]. 15 patients have been treated with dopamine (2.0--6.0 gamma/kg/min) in the initial phase of cardiogenic shock after cardiac surgery. Indication was a systolic blood pressure of less than 85 mmHg associated with oligurie and peripheral vasoconstriction. 12 patients survived the cardiocirculatory crisis and the early postoperative period. Dopamine alone increased the arterial blood pressure in 6 patients from 52.4 to 80.1 mmHg and the urine flow from 25.2 ml/hr to 181.2 ml/hr. To obtain an optimal perfusion pressure additional application of Noradrenalin was used in 8 patients. In these patients the urine flow rose from 9.1 ml/hr to 131 ml/hr. In one patient no reaction, neither to dopamine, nor in combination with Noradrenalin was seen. The effect of pulse rate, central venous pressure and arterial oxygen tension has been discussed. Dopamine seems to be a useful substance in surgical patients with temporary cardiac insufficiency.


Diagnostic and therapeutic considerations for fecal impaction. During an 18-month period, 18 patients were admitted to the Beth Israel Hospital because of fecal impaction or its complications. The records of the 18 patients were reviewed to determine the presenting signs and symptoms, radiologic findings, course and etiology of fecal impaction. Prior use of drugs that slow gastrointestinal motility was found in seven cases, and seven of the 18 patients had severe neuropsychiatric illness. The presenting signs and symptoms in almost all instances were consistent with a diagnosis of intestinal obstruction. The difficulty in differentiating intestinal obstruction caused by fecal impaction from obstruction resulting from other lesions is discussed. The diagnosis of fecal impaction should be entertained only after other causes of intestinal obstruction have been excluded.


[Endoscopic polypectomy of the upper gastro-intestinal tract: results and clinical features (author's transl)]. 247 polyps were removed by electroresection through an endoscope (and 240 recovered) in 160 patients, aged 24-81 years. The histological substrate varied widely. Comparison of histological findings in the biopsy specimen with those of the entire polyp after polypectomy gave differing results in 41 of 87 gastric polyps. Complication rate of endoscopic polypectomy was 1.6%: postoperative bleeding occurred in three, which was treated conservatively, while in one patient ligation of a blood vessel by laparotomy became necessary. There were no perforation or lethal complications. Among three patients with hyperplasiogenic gastric polyps a "borderline lesion" was found in two (early carcinoma type I; adenocarcinoma). In 13 other patients with hyperplasiogenic polyps follow-up examination after one year revealed recurrence in three, absence of polyps in eight. In one patient a small gastric carcinoma (about 1 cm in diameter) was discovered four months later. It is possible that patients with hyperplasiogenic polyps are at a higher risk of cancer. Six-monthly endoscopic observation is, therefore, indicated.


[Multiple cartilaginous exostoses with polyposis of stomach and colon: a new, hereditary combination different from Gardner's syndrome (author's transl)]. Multiple cartilaginous exostoses were found in a 41-year-old man and his two sons, aged 11 and 15 years. The older boy had extensive polyposis of the sigmoid colon and gastric antrum, his brother had radiological changes suspicious of sigmoid polyposis, while there was no radiological evidence of polyposis in the father. None of them had any symptoms of polyposis. The described combination of findings suggests a separate entity from Gardner's syndrome, perhaps on the basis of a combined dominant gene inheritance. In case of multiple exostoses radiological and endoscopic examination of the gastro-intestinal tract for polyposis are indicated.


Blood glucose and plasma insulin levels during prolonged pentobarbitone anaesthesia in the rat. Experiments were conducted on 18 hr fasted male Wistar rats at 15 minutes (short-term anaesthetised) and 5 hr (long-term anaesthetised) after the induction of anaesthesia with sodium pentobarbitone, 45 mg/kg body weight intraperitoneally. Long-term anaesthetised animals received supplementary injections of anaesthetic, 10 mg/kg body weight at hourly intervals, or as required to maintain anaesthesia. Normal basal arterial blood glucose and plasma insulin levels were well maintained during 5 hours of anaesthesia. Following an intravenous glucose challenge, plasma insulin levels and insulin-glucose ratios were slightly reduced in the long-term anaesthetised animals, but glucose tolerance was not significantly impaired. The insulin secretory capacity of pancreas pieces isolated from short-term and long-term anaesthetised animals and incubated in vitro in the absence and presence of glucose was not significantly altered. The hypoglycaemic effect of an intravenous injection of insulin was markedly diminished and the rate of elimination of insulin from the circulation was significantly increased in the long-term anaesthetised animals. These observations indicate adjustments of the glucose homeostatic mechanism during prolonged pentobarbitone anaesthesia in fasting rats.


Effect of hypophysectomy on the volume and ultrastructure of zona glomerulosa in rat adrenal. The zona glomerulosa of the rat has been examined at various times after hypophysectomy. There is no detectable change in the zona glomerulosa at 2 days after hypophysectomy. However by 7 days, the width of the glomerulosa became significantly larger in spite of an absolute decrease in the volume of the zone. No alternations in ultrastructure were discernible at this time in the glomerulosa, although giant mitochondria were seen in adjacent zona fasciculata cells. By 30 days there was a much wider zona glomerulosa and a restoration of the volume of the zone to that found in controls. Many zona glomerulosa cells were hypertrophic. The Golgi apparatus was enlarged and many vesicles were associated with peripheral cisternae. A few intramitochondrial tubules were observed in some mitochondria of the zona glomerulosa at 30 days.


Modified technique of perfusion of isolated rat pancreas tested by insulin release after glucose administration. A method of in vitro perfusion of isolated rat pancreas in a closed circuit is presented. The surgical procedure was slightly modified as compared to the methods published by others the superior mesenteric and coeliac arteries being fixed with tubings for the arterial inflow and the portal vein for the venous outflow. When the attached duodenum is perfused too, it is possible to study both the pancreatic and duodenal excretion. The perfusion of the pancreatic tissue was made with the aid of original equipment. The secretion of insulin into the perfusion fluid after the administration of glucose was measured by radioimmunoassay and a rapid increase of insulin level was found. This observation together with several histological aspects were considered to show the unimpaired viability of tissue.


Influence of plasma hemostasis on insulin action in vitro. The influence of various components of plasma hemostatic system on the assimilation of glucose by isolated rat hemidiaphragm in the presence of insulin was investigated. The addition of streptokinase and human plasminogen to the incubation medium decreased the rate of glucose assimilation. This effect did not occur when trasylol, an inhibitor of plasmin, was added to the assay system. The glucose assimilation by hemidiaphragms incubated in buffer with glucose and insulin was not influenced by thrombin, fibrinopeptides, fibrin degradation products, plasminogen, streptokinase or trasylol added separately to the assay system. The mechanism of the influence of plasmin on insulin action was partly elucidated in further experiments. Thus, less 125I-insulin was bound by isolated fat cells preincubated with plasmin than by control cells.


Effect of epinephrine on adipose tissue metabolism in goats. In adipose tissue of large omentum the release of non-esterified fatty acids (NEFA) was stimulated by epinephrine at concentration as low as 0.25 mug/ml. The stimulation increased sharply within the range of 1-10 mug epinephrine per ml and reached a maximum at 10 mug/ml. The incorporation of glucose and acetate into fatty acids and that of glucose into glycerol decreased with increasing concentration of epinephrine in the incubation medium. In the absence  of glucose and acetate in the incubation medium, hydroxybutyrate at concentrations within 0.96-96 mM decreased significantly either the spontaneous lipolysis or that stimulated by epinephrine. In the presence of 2.5 mM glucose and 5 mM acetate in the incubation medium, beta-hydroxybutyrate did not significantly inhibit the mobilization of NEFA stimulated by epinephrine even at a concentration of 96 mM. In contrast, it accentuated the effect of epinephrine on the decrease of synthesis of fatty acids de novo and on the increase of reesterification of fatty acids. These results indicate that glucose and acetate may counteract the inhibitory effect of beta-hydroxybutyrate on lipolysis.


Gomori-positive cells in rat thymus: Lack of evidence on endocrine function. Large Gomori-positive cells were observed in rat thymus after hormonal induction (e. g. after treatment with oxytocin or hydrocortisone). In contrast to some findings by others, no evidence on endocrine function of these cells was found and they were identified as macrophages containing, in their cytoplasm, great amount of phagocytized material.


Thyroid state and brain monoamine metabolism. The rates at which rat brain synthesizes catecholamines and serotonin were estimated by measuring the accumulation of DOPA and 5-hydroxytryptophan (5-HTP) 45 min after ip administration of the decarboxylase inhibitor RO4-4602 (800 mg/kg BW). Following thyroparathy-roidectomy, hypothyroid rats showed a decreased accumulation of both precursor amino acids. On the other hand, hyperthyroidism (caused by administering 15 mug T4/100 g BW for 25 days) accelerated the accumulation of catecholamines and serotonin. The accumulation of 5-HTP correlated closely with brain tryptophan concentration in all treatment groups; DOPA accumulation, however, did not similarly correspond to brain tyrosine levels.


The ACTH-releasing hormone of the hypothalamus requires a co-factor. Gel filtration of an extract of rat median eminence tissue in 0.1 N HCl on Sephadex G-25 separated two peaks, both with feeble ACTH-releasing activity. Full activity of the extract was regained when both peaks were recombined. This observation suggests that the ACTH-releasing hormone of the hypothalamus requires a co-factor for activity.


Trypsin-kallikrein isoinhibitor K (type Kunitz) from snails (Helix pomatia). Purification and characterization. A basic proteinase inhibitor, isoinhibitor K, was purified by SE-Sephadex C-25 column chromatography from the mixture of acid-stable and heat-stable isoinhibitors of the snail (Helix pomatia). Isoinhibitor K is homogeneous in polyacrylamide gel, cellulose acetate and polyacrylamide-dodecylsulfate electrophoresis. From the electrophoretic mobility in dodecylsulfate-polyacrylamide gel and apparent molecular weight of 6500 +/- 200 was estimated. From the amino acid composition the inhibitor consists of 58 amino acid residues. It contains three disulfide bridges, a C-terminal valine and a lysine residue at the reactive site. Isoinhibitor K inhibits the enzymes: bovine trypsin and chymotrypsin, porcine plasmin and pancreatic kallikrein, the trypsin-like component of Streptomyces griseus proteinase-pronase E, and fungi proteinase K from Tritirachium album Limber, which is only inhibited very slightly in contrast to the effect of the mixture of isoinhibitors. The inhibitory effect of isoinhibitor K against these enzymes is compared to that of the mixture or of other isoinhibitors. The following enzymes are not inhibited by isoinhibitor K: Aspergillus proteinase P and alkaline bacillus proteinase 2231 (Röhm), which both are inhibited by the mixture of isoinhibitors. Porcine elastase, bacterial proteinase N (M) (Röhm), and a trypsin-like proteinase from wheat are not inhibited, porcine acrosin and porcine serum kallikrein only to a very minor extent by the mixture of isoinhibitors. Reactive-site peptide-bond cleavage during inhibition could not be detected. Thus, the inhibitory behaviour is just as broad in specificity and as unusual as that of the trypsin-kallikrein inhibitor (Kunitz) from bovine organs. The N-terminus is blocked by pyroglutamic acid. Isoinhibitor K is the main component of the isoinhibitors secreted into the mucus and amounts to 35-40% of the mixture.


Trigeminal representations of the masticatory and extraocular proprioceptors as revealed by horseradish peroxidase retrograde transport. Horseradish peroxidase has been injected in the masticatory and extraocular muscles in newborn and adult cats to identify the cells of origin for the muscle endings. Labeled motoneurons in the nuclei of the III, IV, V and VI nerves have been observed. They are the parent cells of the motor terminals taking up the enzyme in the muscle injected. Labeled ganglionic cells have been found scattered all along the ipsilateral mesencephalic nucleus of the V nerve after injection of both the jaw closing and the jaw opening muscles. Labeled cells have also been found in the ipsilateral caudal part of the same nucleus after injection of the extraocular muscles. These results are interpreted as due to enzyme uptake by the sensory endings of the muscle studied. Moreover cell bodies in the semilunar ganglion were found marked for both groups of muscles injected showing a second ganglionic representation for the sensory endings.


Age-dependence of spontaneous delayed hypersensitivity to DNA, antinuclear antibody production and development of glomerulonephritis in NZB mice. In NZB mice of different ages (2, 4, 8, 12, and 16 months) the positivity of the migration inhibition test performed with the ds-DNA in spleen explants was compared with the level of immunofluorescent antinuclear antibodies and the incidence of glomerulonephritis. The positivity of the MIT was apparent at 4 months of age, rose with ageing and decreased after 12 months of age. Production of ANA began later, mostly at 8 months of age, increased progressively with ageing, especially in female mice, and was followed by the development of glomerulonephritis which reached its peak at 16 months of age.


On the role of the reticular-epithelial complex in transplantation of the thymus. Transplantation of the neonatal thymus, into young, adult hosts, resulted in massive cell death of graft cortical lymphoid tissue with apparent selective survival of the reticular-epithelial cells. The central area of the graft was progressively cleared of cell debris and the characteristic thymic architecture restored within fourteen days of grafting. Evidence obtained from the regeneration of different-sized transplants suggested that the size and shape attained by the regenerated graft was closely related to the size and shape of the donor tissue. When donor rat thymuses were transplanted in Millipore chambers, the lymphocyte population did not reappear and after seven days only reticular-epithelial cells remained, retaining their normal appearance. However, when these thymic remnants were removed from the chambers and transplanted into secondary hosts, the thymus regenerated normally, suggesting that the lymphocytes in the regenerated gland were derived from the host. Thymic remnants after cortisol treatment of donors also formed distinct organs after grafting despite the fact that they contained few donor lymphocytes. From the differential effects of cortisol on host and transplanted thymus and the different growth characteristics of transplants it appears that transplants differ in their growth/involution control system from the host thymus.


Resection of left ventricular aneurysm. Report of 277 patients. The prognosis of patients with LVA (left ventricular aneurysm) treated medically has been uniformly poor. Surgical resection of the ventricular aneurysm has been the treatment of choice at the Texas Heart Institute since 1958. A more accurate evaluation of patients with LVA by selective coronary arteriography has demonstrated significant associated CAD in over 75 percent of these patients. Since 1969, 125 patients with at lease one vessel suitable for bypass (group II) have undergone single, double or triple ACB in association with LVA resection; and 51 patients (group III) without significant conc-omitant CAD underwent LVA resection alone. To evaluate the efficacy of combined ACB and LVA resection, patients in group II and group III were compared to a third group of 101 patients who underwent LVA resection alone from 1958 to 1969 (group I). Operative mortality was higher in group I (19.8%) as compared to group II (12.8%) and group III (9.5%). Higher mortality was found to be related to a coronary artery score above 8.9, presence of left main coronary lesion, posterior or inferior location of the LVA, severe concomitant mitral valve insufficiency and incomplete revascularization of the remaining ventricular myocardium after LVA resection. Lower mortality and improved long-term results found in groups II and III as compared to group I appear to justify our choice of a "complete operation" in patients with LVA.


[Aorto-coronary bypass. On 200 cases surgically treated (author's transl]. 200 patients underwent bypass graft for treatment of severe coronary vessel disease. The bypass vein grafts were 316; single grafts in 100 cases, double in 85, triple in 14 and in 1 case a patient received 4 grafts. In 57 cases a previous coronary endarterectomy was performed. The flow in the graft at the end of the operation was more than 40 cc/min. in 80% of cases. 22 patients died. Postoperative myocardial infarction occurred in 14% of the patients. The mortality was higher in the preinfarction angina group, and less in the chronic angina group without concomitant surgery (7,2%) and is statistically in direct relation to the functional condition of the left ventricle (2,8% in patients with end diastolic left ventricular pressure less than 20 mmHg and without akinetic areas). Relief of angina was observed in 87% of the surviving patients. Postoperative coronarography, catheterism and left ventriculography was performed in 46 patients. Only 2 of the 15 cases with postoperative angina had the graft patent. Significant improvement of the left ventricular function with disappearence or regression of akinetic areas was observed in 9 patients. Our experience indicates that the value of this operation cannot be entirely known at the present time.


[Phytomitogen-induced lymphocyte transformation - standardization and diagnostic value (author's transl)]. Lymphocytes can transform into blasts. This basic biological property is the prerequisite for many reactions of the cellular immune system. Therefore, lymphocyte transformation tests appear to be a valuable diagnostic approach to define primary and secondary immundeficiency associated with different diseases. The validity of the test system is based on a standardization wich can be achieved sufficiently with regard to culture conditions and measurement of DNA-synthesis. But for phytomitogen-induced lymphocyte transformation a cooperative system of lymphocytes and macrophages is necessary. The results are influenced to a high degree by different cell separation procedures. Therefore, the interpretation of abnormal lymphocyte transformation data, induced unspecifically mitogens, has to take into account alteration of lymphocyte function, different T-/B-cell ratios and changing counts and helper effects of macrophages in order to define a defective lymphocyte transformation more precisely.


[Analysis and differentiation of cytergic immune reactions: tuberculine type and cutaneous basophilic hypersensitivity (author's transl)]. The classic delayed tuberculine reaction represents a T-cell mediated immune reaction, detectable already before the formation of antibodies in the course of proteine sensitization. Myocobacteria stimulate and enhance this reaction. The skin test reaction needs the whole antigen for induction. The reaction starts 6 to 8 hours later, shows maximal development 24 to 28 (-72) hours later and is characterized by inflammation, induration, sometimes with hemorrhagies, necroses and ulceration, a macrophage infiltration is typical in the histological picture. During the reaction between antigen and sensitized T-cells mediators are set free which act by the way of unspecific stimulation on T-, B-lymphocytes and macrophages, otherwise they may inhibit macrophage migration. The delayed reaction is active in many infectious diseases and in the rejection of transplants and tumours. The cutaneous basophilic hypersensitivity (Jones-Mote) is a T-cell mediated immune reaction, detectable even before the classic delayed reaction after sensitization with tiny up to large doses of proteines. The skin reaction needs the whole antigen for induction, is visible 2 to 4 hours later in form of an inflammation with slight swelling and reaches maximal development 12 to 24 hours later without hemorrhagies or necroses. The infiltration consists mainly of basophilic leucocytes. There exists a weaker avidity of the T-cells of the cutaneous basophilic hypersensitivity compared to the T-cells of the delayed reaction or to the amount of antibodies. Therefore this reaction is easily suppressed by other immune reactions. In contactdermatitis and vaccine virus infections of the guinea pig the cutaneous basophilic hypersensitivity consists for weeks and months because under these circumstances other immune reactions do not compete. The differentiation of the two reactions shall develop to a routine laboratory procedure due to their therapeutic consequences in the immune diagnostic field.


[Humoral immune phenomena in acute and chronic viral hepatitis (author's transl)]. During HBAg positive acute viral hepatitis transitory antibodies of a low titer against smooth muscle, vascular endothelium, nuclei, and liver cell membrane antigens (polygonal pattern of immunofluorescence) occur. In HBAg positive chronic aggressive hepatitis, sometimes antibodies against nuclei or smooth muscle are associated with HBAg. Their occurrence heralds an unfavorable prognosis. High titer antibodies against nuclei and smooth muscle - a typical serology finding in lupoid chronic aggressive hepatitis - and mitochondrial antibodies have not been observed in a HBAg positive hepatitis. Subdividing chronic hepatitis in six different groups is possible with HBAg and antibodies. The predominance of histocompatability antigen HLA 8 in lupoid hepatitis and a lack of this leukocyte antigen in HGAg positive chronic aggressive hepatitis suggests that in the various forms of hepatitis, a different susceptability and capability for immune response towards microorganism is reflected. It is postulated that for course and outcome of hepatitis, the type of immune reaction plays a decisive role.


Rosette formation with mouse erythrocytes: probable marker for human B lymphocytes. Studies of peripheral blood lymphocytes were performed in 10 healthy control subjects and 15 patients with hematological disorders. Spontaneous formation of mouse red blood cell-forming rosettes (MRFC) were observed with 8.1% of lymphocytes in control subjects (range 4.2--12.0%), while rosette formation with sheep red blood cells (SRFC) and complement-coated sheep erythrocyte (EAC rosettes) was present in 69.2 and 10.7%, respectively. Mouse rosette-forming cells were increased in parallel fashion with EAC rosettes in five patients with chronic lymphocytic leukemia suggesting that mouse red blood cells (MRBC) may serve as a B cell marker. A single patient with a lymphoma associated with increased peripheral SRFC did not have a concomitant rise of MRFC. It appears likely that MRBC will provide another detection marker for B lymphocytes by spontaneous rosette formation.


Bacteriophage MS-2 in the immune response. Several aspects of the immune response to bacteriophage MS-2 were studied. In thymectomized, irradiated and bone marrow-reconstituted (TXBM) mice, the response was normal when a high dose of antigen was used. With a 50-fold lower dose of MS-2, the response was impaired, indicating a T-cell involvement in antibody formation. More evidence for the (partial) T-cell dependence of MS-2 was obtained from experiments with anti-thymocyte serum or cyclophosphamide-treated mice. (3H)-thymidine incorporation experiments demonstrated that both B and T cells were active upon in vitro stimulation with MS-2. The dose of MS-2 which was able to induce a normal response in TXBM mice, proved to be optimal for both sensitization and elicitation of a DH. It is concluded that MS-2 is a thymus-dependent antigen which is only thymus independent in high doses.


Carrier effect by Nippostrongylus brasiliensis infection on rat antihapten IgE antibody response. Nippostrongylus brasiliensis infection was found to be highly effective in inducing a carrier-specific enhancing effect on primary and secondary antihapten IgE antibody response in the rat, when animals were immunized i.p. with 10 mug of dinitrophenylated N. brasiliensis protein (DNP-Nb) plus 10 mg Al(OH)3 2 weeks after the infection. The carrier effect by the infection was much greater than that obtained by any other supplementary immunization with the carrier (Nb) plus adjuvant, so far examined, in terms of the IgE antibody response. The results, together with our previous observation in the mouse, provide an explanation for the reason why antiworm IgE antibodies are so easily detectable in helminth infections.


Host responses within solid tumors: non-thymus-derived specific cytotoxic cells within a murine mammary adenocarcinoma. The nature of host-derived, specifically cytotoxic cells infiltrating solid murine mammary adenocarcinomas (line T1699) was investigated. Cell suspensions obtained from enzymatically dispersed tumors were separated by sedimentation velocity. The host cell fraction was heterogeneous and contained T-lymphocytes, non-phagocytic cells bearing Fc receptors, eosinophils and monocytes. Host cells equivalent in size to small lymphocytes and bearing Fc receptors were found to be the predominant cell type responsible for colony inhibition. These colony-inhibiting cells were insensitive to lysis with either anti-theta or anti-IgG serum and complement; and they were specific both in their induction and in their mediation and in their mediation of cytotoxicity. Host cells made up the predominant population in spontaneously regressive tumors but only a minor component in progressive tumors, and they were totally absent from progressive tumors in X-irradiated animals.


The effect of radiation on processing of nuclear RNA and chromatin ribonuclease activity in rat liver and thymus. The effect of radiation on the kinetics of nuclear RNA degradation was studied during actinomycin chase. The intranuclear breakdown of RNA in thymus was inhibited for the first 30-120 min after 800 R irradiation of rats. In liver the degradation of nuclear RNA was unchanged for 60 min after irradiation. By the second hour, the breakdown of the rRNA precursor accelerated and the processing of D-RNA slowed down. Rat thymus and liver chromatin showed RNAase activity with two optimal pHvalues- in the acidic (pH 5-0-5-5) and weakly alkaline (pH 7-5) regions. The activity of the acidic RNAase of thymus (but not the liver) chromatin fell after 5-20 kR irradiation in vitro. The activity of the alkaline RNAase did not change under these conditions. The data indicate that a fall in activity of the acidic RNAase in irradiated thymus chromatin may be related to disturbance in the enzyme-inhibitor interaction. A possible contribution of the chromatin acidic RNAase to the processing of nuclear RNA in control and after irradiation is discussed.


Energy requirements for damaging DNA molecules. III. The mechanisms of inactivation of bacteriophage chiX 174 DNA by vacuum ultra-violet radiation. Strand break formation and biological inactivation of infectious DNA of bacteriophage phi chi 174 exposed to vacuum-ultra-violet radiation of 4-9 to 21-2 eV quantum energy is investigated. At 21-2 eV as many as 84 per cent of the DNA molecules are inactivated by breaks whereas breaks do not contribute to inactivation at 4-9 eV. The quantum yield of break formation increases from 1-7 X 10(-5) (4-9 EV) to 0-55 (21-2 eV) and shows a dependence on energy similar to that of electron emission (due to ionization) above 8 eV. The mechanisms leading to break formation and inactivation are discussed taking the absorption spectrum of DNA in the vacuum-ultra-violet region into consideration.


Further studies of DNA damage and lethality from the decay of iodine-125 in bacteriophages. The DNA of coliphages T4 and T1 was labelled with 125I-iododeoxyuridine. 125I decay is known to cause severe molecular damage via vacancy cascades (the Auger effect). We have compared the induction of both single- and double-strand breaks (SSBs and DSBs) in 125I-labelled T4 DNA stored at - 196 degrees C during decay, either as intact phage or as free DNA. These comparative experiments indicate that, in addition to one DSB which apparently results directly from the Auger effect, each decay in an intact phage also give rise to an additional 0-05 DSBs, as well as 1-6 SSBs, as a result of ionizing radiation absorbed in the same phage particle where the decay occurs. An examination of T4-killing by 125I decay reveals a two-phase survival curve, whose initial slope corresponds to a lethal efficency per 125I decay of 0-95 +/- 0-05, which is considerably higher than values previously determined. The results for phage T4, and of a more limited comparison of 125I suicide and DNA damage in phage T1, support the hypothesis that the vacancy cascades which accompany each 125I decay in DNA result in a double-strand break at the decay site and that each such break is a lethal event.


Radiation dose from plutonium deposited in marrow and bone of normal and chimaeric mice. 239Pu citrate was injected intraperitoneally into CBA mice and into CBA mice which had been made chimaeric by replacing their haematopoietic bone-marrow with that from another genetically-identical but cytologically-distinct strain. The mice were killed at three intervals up to 90 days after injection, and the deposited 239Pu was determined radiochemically in bone-marrow and in bone. The average radiation dose (integrated over 90 days) was found to be greater in the bones but lower in the marrow of chimaeric mice than in the corresponding tissues of the normal CBA mice. These results are discussed from the points of view of induction of malignant change in marrow and bone and of plutonium metabolism in the two types of mouse.


Modification of the radiosensitivity of barley seed by post-treatment with caffeine. Kinetics of decay of caffeine-reactive oxygen-sensitive sites. In dry barley seeds (3-1 per cent moisture content), the maximal level of oxic damage (class III damage) is reached within the first 40 min of post-hydration in oxygenated water at 5 +/- 1 degrees C. The decay of the gamma-ray-induced oxygen-sensitive sites requires, however, about 120 min. The mechanisms leading to partial protection against the class III damage are initiated when caffeine is present during the first 30 min of oxygenated post-hydration. If added after 30 min of oxygenated hydration, caffeine has no protective action. For the potentiation of an oxygen-independent component of damage, caffeine has to be present during the first 240 min of oxygen-free hydration. These observations involving a physiologically inert system raise questions regarding physico-chemical vis-a-vis biochemical mechanisms of caffeine effect on irradiated systems and these have been briefly discussed.


Oxygen--effect on strand breaks and specific end-groups in DNA of irradiated thymocytes. Thymocytes were irradiated with fast electrons up to 6 Mrad in the presence and absence of oxygen. The cells were treated before irradiation with a cold shock to prevent any repair rejection during irradiation. The DNA isolated subsequently was analysed for double-strand breaks (dsb), actual single-strand breaks (ssb) and alkali-induced strand breaks (alisb). We observed a linear increase of all types of lesions with dose and an o.e.r. for dsb of 3-6, for ssb of 4-9 and for alisb of 2-1. The data do not deviate significantly from those, measured on thymocytes irradiated without cold shock. In DNA of irradiated thymocytes, the frequency of 3' and 5' hydroxyl and 5' phosphate end-groups was analysed enzymatically. In both the ssb and alisb, about 11 per cent of the terminals carry 5'OH end-groups and 20-40 per cent 5' phosphate groups. On the 3' terminals, 60-80 per cent of the ssb are identified as 3'OH end-groups, whereas on the alisb only a small amount of 3'OH end-groups if found. The frequency of characterized end-groups shows the same oxygen effect as the corresponding strand breaks. Therefore, in the presence and absence of oxygen, the same mechanism may be responsible for formation of DNA strand breaks in vivo.


Radiosensitivity and hydroxyl radical reactivity of phosphate esters as measured by radiation-induced dephosphorylation. The yields of inorganic phosphate from irradiated phosphate esters of biological interest have been measured in the presence of various free-radical scavengers. These studies indicate that hydroxyl radical attack on the phosphate esters accounts for most of this damage. Competition kinetics using different hydroxyl radical scavengers whose reactivities are known have been used to estimate the rate-constants for the overall hydroxyl radical reactivities of the phosphate esters. The extent of hydroxyl-radical-induced dephosphorylation is very low for nucleotide derivatives, but high for some sugar and glycerol phosphates, reflecting the probability of hydroxyl radical abstraction at the alpha or beta carbon atoms adjacent to the phosphate ester linkage. The hydroxyl radical reactivities of nucleotides, coenzymes, sugar phosphates and phospholipid components are all high (1-10 X 10(9) M-1 sec-1), indicating the importance of hydroxyl radical attack in the inactivation of these components in living cells, although not necessarily by dephosphorylation.


Viruses in osteosarcomas induced by 226Ra. A study of the induction of bone tumours in mice. Three groups (15 in each) of 3-month-old mice were injected intraperitoneally with 0-5 muCi 226Ra. They were male and female C3H/H and female CBA/H. The groups were matched by similar controls that were not injected. Osteosarcomas were found in 14/15 of the female C3H/H mice--animals known to carry mammary-tumour viruses in milk--compared with 6/15 in their male counterparts. In CBA/H female mice, which have a very low incidence of both mammary tumours and leukaemia, osteo-sarcomas developed in 7/15 of the animals. The CBA/H mice lived about 5-8 months longer and revealed their osteosarcomas at a correspondingly later time than C3H/H mice. Virus particles were observed in each of the three mammary tumours and in 15 out of the 17 osteosarcomas examined by electron microscopy. No definitive statement can be made from this experiment whether or not osteosarcoma was caused by a virus; but the results suggest that viruses may be a contributory factor in the development of osteosarcoma in these animals.


Radioprotection of lipogenesis from glucose (U-14C) and activities of pyridine nucleotide dehydrogenases in liver of gamma-irradiated female rats by cystamine. Whole-body gamma-irradiation (1200 R) of female rats significantly increased liver glycogen and incorporation of glucose (U-14C) into liver fatty acids. Administration of cystamine before irradiation protected the enhanced lipogenesis from glucose (U-14C), but afforded only a partial protection of liver glycogen levels. Irradiation significantly decreased the activities of liver pyruvate kinase and isocitrate dehydrogenase, and this decrease was not prevented by the administration of cystamine before irradiation. A significant increase in the activity of liver malate dehydrogenase (dehydrogenating) was noted in irradiated rats, which was not prevented by the administration of cystamine before irradiation. Irradiation did not affect the activities of combined hexose monophosphate pathway dehydrogenases and of malate dehydrogenase (decarboxylating).


Influence of rat blood on radiation protection of mammalian cells by cysteamine and cystamine in vitro. The protective effect of cystamine and cystamine on T-cells in normal growth-medium was studied in the presence of whole rate blood (WRB). The protective effectiveness of both agents was increased by the addition of WRB, but much less so on the activity of cystamine. In the presence of WRB a dose-reduction factor of 1-5 was obtained at the low concentration of 0-05 mM cysteamine. The increase in protection was not due to induction of anoxia or to a release of glutathione from the rat red cell. The increase in protection may be due to protector RS radicals reacting with rat red cells.


Quantitative dose-response of growth and development in Arabidopsis thaliana exposed to chronic gamma-radiation. The response of Arabidopsis thaliana (L.) Heynh. (Cruciferae) to a gradient of chronic gamma-radiation was examined under field conditions. Plants that were initially introduced to the gamma field as dry seeds received exposures of 1-34 to 18 800 R/20 hour day from the time of seed germination. Regression analysis demonstrated a significant, but non-linear, response for three variables, number of seedlings emerging, number of plants flowering, and plant volume; the response of a fourth variable, number of leaves per plant, was not related to daily exposure. LD50 values ranged from 66 R/20 hour day for plant volume to 1231 R/20 hour day for seedling emergence. Flowering and plant volume were the most sensitive indicators of radiation exposure. The demonstration of a variable threshold at low levels of exposure indicates that in nature A. thaliana may be exposed to environmental radiation throughout its life-cycle without significant modification of growth or development.


The relationship between chromosome aberrations and low LET radiation dose to human lymphocytes. In vitro dose-response curves of unstable chromosome aberrations in human lymphocytes have been obtained for 250 kV X-rays and cobalt-60gamma-radiation. The aberration yields have been fitted to the quadratic function Y = alphaD +betaD2, which is consistent with the single-track and two-track model for aberration formation. The values of the coefficients alpha and beta support the hypothesis that the dose-rate effect is limited to the D2 term. The main difference between the coefficients for X- and gamma-radiation is in the alpha values, indicating that X-rays are slightly more efficient, at lower doses, in producing two lesions with a single ionizing track. The lower limits of dose estimate, with 500 cells analysed, are 4 rad for X-rays and 10 rad gamma-radiation. Further evidence is presented confirming that, for cytogenetic dosimetry, in vitro dose-response curves should be prepared by irradiating whole blood maintained at 37 degrees C and prior to PHA stimulation. Curves were plotted showing the variation of the number of cells without aberrations with radiation dose and the shape of these curves were compared with those from human cell survival experiments.


The electroretinogram in dogs with inherited cone degeneration. The electroretinogram (ERG) of hemeralopic Alaskan malamute dogs contains only rod components. There is absence of the photopic b-wave which is normally elicited with red light stimuli during dark adaptation and, using flicker stimulation, only the first or rod branch of the flicker fusion response curve is present. At high stimulus intensity levels, the flicker response of hemeralopes is absent. A normal ERG is recorded from affected dogs using blue light stimuli and low intensity white light. In the adult hemeralope, the retina contains no cones.


Anti-nucleic acid antibodies in systemic lupus erythematosus patients and their families. Incidence and correlation with lymphocytotoxic antibodies. Anti-RNA antibodies were found in 82% of 28 systemic lupus erythematosus (SLE) probands and in 16% of 124 of their family members. The incidence in 76 control family members was only 5%. In the SLE family members, the antibodies were found exclusively in 21% of the 94 close household contacts of the probands. The incidence of anti-native DNA (nDNA) antibodies was 68% for the SLE probands. The incidence of anti-nDNA antibodies in close household contacts of the probands was 6%, which was not significantly different from the 1% incidence found in control families. Lymphocytotoxic antibodies occurred in 57% of the SLE family members as a whole and in 68% of the close household contacts. In the SLE probands, lymphocytotoxic antibodies correlated with anti-single-stranded RNA (poly A) and anti-nDNA but not with anti-double-stranded RNA (poly A-poly U). On the other hand, lymphocytotoxic antibodies in the household contacts correlated with anti-double-stranded RNA (poly A-poly U) but not with anti-poly A or anti-nDNA. The anti-RNA antibodies were present in consanguineous household contacts but not in nonconsanguineous household contacts. These findings strengthen the hypothesis that both an environmental agent, possibly a virus, as well as the genetic response are important in the pathogenesis of SLE. Family members may therefore be a logical population in whom to search for specific antibodies to a viral agent.


Adult alpha1-antitrypsin deficiency.

Adult alpha1-antitrypsin deficiency. Three adults with alpha 1-antitrypsin deficiency are described. In two of the cases the deficiency was genetically determined (cases 1 and 2), and each demonstrated unusual features of the disease. The liver in case 1 (homozygous) showed cholangiolar hyperplasia which has been recorded only once before. Case 2 (heterozygous) had emphysema and cirrhosis, a combination not previously documented in a heterozygote, in addition to malabsorption. Case 3 represents a case of spurious alpha 1-antitrypsin deficiency with cirrhosis included to emphasize the diagnostic improtance of phenotyping in such cases.


Heterogeneity of human T lymphocytes to bind sheep erythrocytes and mitogenic responses of their subpopulations. Heterogeneity of human T lymphocytes was examined by the rosette formation of sheep red blood cells (E-rosette) in two different reaction media: fetal calf serum (FCS) and gelatin Veronal buffer (GVB). Nearly all the T lymphocytes could form rosettes in FCS at 1 degrees C (FCS-R) independently of the incubation time. In contrast, rosette formation in GVB (GVB-R) was apparently dependent upon the incubation time and could not be used in the enumeration of the total T cells even after long incubation. Among the possible subpopulations, a fraction (T1) that could form GVB-R as well as FCS-R, and the other fraction (T2) that could form only FCS-R were partially purified by rosette formation and by density gradient on a Ficoll-Isopaque layer. In contrast to the T cell-depleted fraction (B) which formed EAC rosettes in a majority of cells and E rosettes in a few cells, only a small portion of cells from both the T1 and T2 fractions could form EAC-rosettes. T1 cells possessed high responses to PHA as estimated by the counts of 3H-TdR incorporation as well as the stimulation indices. In contrast, T2 cells possessed a lower responsiveness to the mitogen, and B fraction cells could not respond at all. These results suggested that a positive correlation exists between the ability of E rosette formation and responsiveness to PHA in the T cell subpopulations. Preliminary experiments also suggested that percentages of T1 cells highly responsive to PHA may decrease and, therefore, those of T2 cells less responsive to the mitogen may increase in the T cell population of the patients with some immunodeficiencies.


Genetic control of the murine cell-mediated immune response in vivo. II. H-2 linked responsiveness to the synthetic polypeptide poly(Tyr,Glu)-poly(DL-Ala)--poly(Lys). Cell-mediated immunity in response to (T,G)-A-L was studied with a radioisotopic footpad assay. It appears that in vivo cell-mediated immune responsiveness to (T,G)-A--L is linked to the H-2 complex, as was demonstrated previously for specific antibody snythesis. Evidence is presented in this report which indicates that the cell-mediated immunity measured is a function of a population of T cells. The apparent controversy between results obtained by analyzing antibody formation and cell-mediated immunity can be explained by assuming the need for cell cooperation between helper T cell and effector T cell, because efficient purely cellular immunity is analogous to T-B cell cooperation needed for antibody production.


Inhibitory effect of Apernyl on production of bradykininlike substance in pulp. In the Formalin-induced pulpitis of rats and the electrically stimulated pulps of dogs, a bradykininlike substance developed by the pulps and released into a saline pool on the exposed pulps disappeared after a local application of Apernyl solution. This suggests that the possible pain-reducing or anti-in-flammatory effect of Apernyl is a result of its inhibiting bradykinin production.


Lack of inverse relationship between the net charge of T-independent immunogens and the responding spleen cells. Previous studies have demonstrated an inverse relationship between the net electrical charge of immunogens and the antibodies they elicit. This correlation was found to be expressed at the cellular level. It has been shown that thymus-derived cells may recognize immunogens on the basis of their overall electrical charge. In this study, charged T-independent copolymers composed of tyrosine, glutamic acid, and lysine of the D configuration were prepared in order to find out whether this net charge phenomenon holds also for immunogens which do not require helper T cells for generation of immune response. Spleen cells were fractionated over negatively charged glass bead columns, and their immunocompetence was tested by transferring them into irradiated recipient mice which were immunized with the dinitrophenylated acidic or basic T-independent carrier. No differences in the responsiveness to the dinitrophenyl group on either carrier could be detected in recipients of unfractionated or fractionated cells on the charged columns. Similar results were obtained with the negatively charged T-independent branched polypeptide poly-(DTyr,DGlu)-poly(DPro)--poly(DLys). Filtration of spleen cells through glass bead columns did not affect the immune response potential of the recipient mice. In contrast, a significant reduction was observed in the frequency of positive responses in recipients of filtered cells, which were immunized with the negatively charged T-dependent poly(DTyr,DGlu)-poly(DPro)--poly(DLys). Thus, the inverse net charge phenomenon holds only for T-dependent antigens.


Effects of anti-Ia serum on mitogenic responses. I. Inhibition of the proliferative response to B cell mitogen, LPS, by specific anti-Ia sera. Specific anti-Ia serum in combination with rabbit complement removed the B lymphocyte population normally responsive to LPS mitogenic stimulation. Significant inhibition of this proliferative response was also obtained by brief periods of cell pretreatment with anti-Ia antibodies, but not with specific anti-H-2K antibodies. The population of splenic B cells resistant to anti-Thy-1.2 serum and complement was blocked in a very similar manner by anti-Ia serum, but not by anti-H-2 serum.


Permanent slide preparations of T lymphocyte-sheep red blood cell rosettes. Rosette formation between sheep erythrocytes (SRBC) and human thymus-derived lymphocytes (T cells) is used to monitor T cells in various human diseases. Rosettes are usually counted in a hemacytometer immediately after preparation. This paper reports a technique for permanently fixing and staining rosettes for serial and comparative studies, a procedure which has probably been less well standardized, less reproducibly performed, and less widely used than many investigators appreciate. The technique describedhas the advantages of providing distinct morphological identification of the rosette-forming cell and it produces a permanent mount for further reference.


Aspects of tail muscle ultrastructure and its degeneration in Rana temporaria. 1. Tail muscles of larval Rana temporaria and to a lesser extent Xenopus laevis, at prometamorphosis, were investigated by light and electron microscopy. In the case of Rana their degeneration is described at metamorphic climax. 2. The non-degenerate tail muscles of both genera are generally similar in their ultrastructure and likewise similar to those striated muscles of other adult vertebrates including amphibians. 3. At climax tail muscles of Rana degenerate by autolysis. It seems likely that lysosomal enzymes are directly involved in sarcoplasmic degeneration. The relationship between lysosomes and myofibrillar degradation is difficult to establish. The subject is discussed in the light of relevant information (mainly mammalian) on muscle dystrophies. 4. Anuran tail muscle is highly degraded before its probable phagocytosis by mesenchymal macrophages.


Visual reaction times during prolonged angular acceleration parallel the subjective perception of rotation. The effect of prolonged angular acceleration on choice reaction time to an accelerating visual stimulus was investigated, with 10 commercial airline pilots serving as subjects. The pattern of reaction times during and following acceleration was compared with the pattern of velocity estimates reported during identical trials. Both reaction times and velocity estimates increased at the onset of acceleration, declined prior to the termination of acceleration, and showed an aftereffect. These results are inconsistent with the torsion-pendulum theory of semicircular canal function and suggest that the vestibular adaptation is of central origin.


Problem-specific coding systems.

Problem-specific coding systems. The data found in medical records, particularly in problem-oriented records, could yield very useful information for many aspects of the health care delivery system. Unless the tools and methods used in the analysis of health care data are very carefully designed, the potential value of this information cannot be fully realized. Coding is a critical step in the process of converting medical record data into useful information. This paper presents six criteria as design goals for a standard, comprehensive, coherent set of nomenclatures, classifications, taxonomies, and corresponding coding schemes for the analysis of medical and administrative record data. These goals are: compatibility with established routine operating procedure, health care problem specificity, hierarchical structure, economy through articulation of the components with one another and through the similarities in various aspects of health care delivery, and adaptability to change.


Characterization of the effects of Mg2+ on Ca2+- and Sr2+-activated tension generation of skinned skeletal muscle fibers. Changes in [Mg2+] in a millimolar range have a significant inverse effect on the Ca2+- (or Sr2+)activated tension generation of skeletal muscle fibers. Single frog (Rana pipiens) semitendinosus muscle fibers were "skinned" (sarcolemma removed) and contracted isometrically in bathing solutions of varying [Ca2+] or [Sr2+] and [Mg2+] but a constant pH, [MgATP2-], [K+], [CP2-], [CPK], and ionic strength. Ca2+- (or Sr2+-)activated steady-state tensions were recorded for three [Mg2+]'s: 5 X 10(-5)M, 1 X 10(-3) M, and 2 X 10(-3) M; and these tensions were expressed as the percentages of maximum tension generation of the fibers for the same [Mg2+]. Maximum tension was not affected by [Mg2+] within Ca2+-activating or Sr2+-activating sets of solutions; however, the submaximum Ca2+-(or Sr2+)activated tension is strongly affected in an inverse fashion by increasing [Mg2+]. Mg2+ behaves as a competitive inhibitor of Ca2+ and also affects the degree of cooperativity in the system. At [Mg2+] = 5 X 10(-5)M the shape of tension versus [Ca2+] (or [Sr2+]) curve showed evidence of cooperativity of Ca2+ (or Sr2+) binding or activation of the contractile system. As [Mg2+] increased, the apparent affinity for Ca2+ or Sr2+ and cooperativity of the contractile system declined. The effect on cooperativity suggests that as [Mg2+] decreases a threshold for Ca2+ activation appears.


Meningiomas of Meckel's cave.

Meningiomas of Meckel's cave. A retrospective review of 12 cases of meningioma of Meckel's cave involving the Gasserian ganglion or the trigeminal posterior root (or both) seen at the Mayo Clinic during a 20-year period suggested three clearly defined clinical groups. One group (the largest) had typical trigeminal neuralgia and an excellent prognosis after the removal of the easily detachable mass that was impinging on the ganglion.  A second group, with meningiomas en plaque embedded in the ganglion, had a history of atypical trigeminal face pain without neurological deficit, but the prognosis for pain relief was not as good as in the previous group. A third group had a history of face dysesthesias and pain, objective trigeminal sensory loss, and multiple cranial nerve deficit; these patients had meningiomas with histological signs of mitotic activity and a poor prognosis, with return of intractable pain and recurrence of the tumor.


Rhabdomyosarcoma of the brain.

Rhabdomyosarcoma of the brain. The authors report a case of rhabdomyosarcoma originating in the fourth ventricle and review the eight comparable previous reports on true rhabdomyosarcoma, composed solely of mesenchymal elements. Tumors in most adults arose in the cerebral hemisphere, while those in children arose exclusively in the midline structures of the posterior fossa. The tumor in the author's case was initially benign and well circumscribed, but within 2 years had changed into a malignant rhabdomyosarcoma. The histological documentation during the interval is presented and discussed.


Ascites from a ventriculoperitoneal shunt. An unusual case of ascites secondary to a ventriculoperitoneal shunt is presented. The ascites did not redevelop following diversion of the distal catheter into the right atrium, and no adequate explantation was found as to why the cerebrospinal fluid was not absorbed by the peritoneum.


Recognition of traffic signals viewed through colored filters. Experiments were carried out to provide an empirical basis for setting color standards for sunglasses. Nineteen individuals, ten with anomalous color vision, viewed traffic signals through a series of color filters. Limits on the apparent color shift for the amber and green signals as well as for D65 are presented on a 1931 CIE chromaticity diagram. Limits on the reduction in the apparent luminosity for each of the three signals are given in terms of the minimum transmittance of the lens for each signal.


Central cavernous hemangioma of the mandible treated by an intraoral approach. We have presented a case of surgical treatment of a central cavernous hemangioma of the mandible in which a radical deforming operation on a 12-year-old girl was avoided. A rather unique surgical approach was devised after all diagnostic criteria were available and after very careful consideration of an operative plan.


Chronic neutropenia: Response to plasma with high colony-stimulating activity. A child with repeated infections was immunologically normal but was found to have neutropenia with periodic elevations of the absolute mature polymorphonuclear count at 21-day intervals. Immediately following the PMN rise, bone marrow morphology and in vitro cultures demonstrated a maturation arrest at the myelocyte stage with an increase in proliferative capacity. His cycle was not altered by infusions of normal plasma or by injections of epinephrine or typhoid vaccine. Infusion of 10 ml/kg of "stimulated" plasma from donors reactive to TV, obtained 60 minutes following immunization, resulted in an out-of-phase rise in PMN cells and clinical improvement. In vitro assays, using normal or patient marrow, detected high levels of colony-stimulating activity only in those plasma samples that were effective in the patient. These observations support a role of CSA as a physiologic regulator of granulopoiesis in man.


Blood pressure and puberty.

Blood pressure and puberty. The purpose of this investigation was to study the relation of blood pressure to sexual maturation in 229 boys and 189 girls, 10 to 14 years of age. The results showed that there was no significant correlation between the systolic and diastolic pressure with the level of serum follicle-stimulating hormone and luteinizing hormone in either sex. Nor was there a significant correlation with the stage of pubic hair development in the boys nor with the stage of breast development, menarche, and duration since menarche in the girls. Therefore the presence of hypertension during 10 to 14 years of age should not be regarded as a physiologic response to pubertal development, but rather as a suspicious finding which deserves careful follow-up examinations.


Portal hypertension in children following neonatal umbilical disorders. 10 children presented pre-hepatic portal vein obstruction during their first 6 years of life. 8 of them had massive esophageal varices, 1 died from acute esophageal hemorrhage. The perinatal history of these childre was studied: All of them had an abnormal birth history and all had been hospitalized during their neonatal period. In 5 of them an umbilical infection had been diagnosed, one had an injection of THAM and one other an exchange transfusion through an umbilical vein catheter. Pre-hepatic portal vein occlusion in children is presumed to be mainly an acquired disease resulting from neonatal umbilical disorders.


Mechanism of frequency-dependent inhibition of sodium currents in frog myelinated nerve by the lidocaine derivative GEA. A new lidocaine derivative (Astra, GEA 968) depresses excitability of myelinated frog nerve in a manner which depends upon the rate of use of the nerve. This phenomenon has been shown, under voltage clamp conditions, to involve "frequency-" or "use-dependent" inhibition of the transient inward sodium currents at the node of Ranvier. With 0.6 mM GEA 968 in the solution bathing the node, the inward sodium currents produced by 5-msec depolarizing pulses to -20 mV are reduced to 40% of control values if the node is rested for a few hundred seconds prior to the test pulse. Repetitive opening of the sodium channels by depolarizing pulses enhances this inhibition, for example, currents are eventually reduced to 10 to 20% of control with repetitive depolarization at 2 sec-1. If the preparation is then allowed to rest, this use-dependent increment in inhibition gradually declines with a time constant of about 10 seconds. Repetitive opening of the sodium channels by depolarizing pulses preceded by large hyperpolarizing prepulses reverses the inhibition caused by application of depolarizing pulses alone. It is hypothesized that the GEA 968 molecule binds to open sodium channels and, in doing so, simultaneously blocks the channel and shifts the curve relating sodium inactivation to membrane potential by 20 to 40 mV in the hyperpolarizing direction. Several kinds of evidence supporting this molecular hypothesis are presented. Lidocaine, procaine, procaine amide and a quaternary lidocaine derivative QX-314 also cause use-dependent depression of sodium currents in this preparation. This common mode of action of tertiary and quaternary anesthetics implies that the cationic form of tertiary anesthetics is active.


Voltage dependence of agonist effectiveness at the frog neuromuscular junction: resolution of a paradox. 1. End-plate currents produced by nerve-released acetylcholine and iontophoretically applied acetylcholine and carbachol have been recorded from voltage-clamped frog cutaneous pectoris neuromuscular junctions made visible with Nomarski differential interference contrast optics. 2. The effectiveness of agonists - that is, the end-plate conductance change produced by a given dose-has been determined as a function of post-junctional membrane potential. 3. As the post-junctional membrane potential is made more negative, nerve-released acetylcholine becomes less effective whereas iontophoretically-applied agonists become more effective. 4. This voltage dependence of agonist effectiveness is mediated neither by end-plate current iontophoresis of agonist into the cleft nor through electric field effects on the esterase. 5. Influences of membrane potential on the opening and closing of end-plate channel gates can account quantitatively for the voltage-dependent effectiveness of both nerve-released and iontophoretically applied agonist.


Intracellular chloride activity in frog heart. 1. Chloride liquid ion exchanger micro-electrodes have been used to measure intracellular chloride activity (aiCl) in isolated pieces of frog sinus venosus, atrium and ventricle. 2. aiCl was found to be 35-0 +/- 3-2, 17-3 +/- 0-8 and 17-6 +/- 0-8 mM in sinus venosus, atrium and ventricle, respectively. 3. In atrium and ventricle aiCl is independent of whether the tissue is beating or non-beating. 4. In non-beating ventricle aiCl changes rapidly and reversibly when aOCl is reduced by replacing chloride with glucuronate. 5. ECl calculated from the measured aiCl has been compared with ECl calculated from the constant field equation assuming either constant chloride conductance or constant chloride permeability. 6. It is suggested that chloride is actively transported into the cells in all three kinds of frog heart tissue.


The effect of zinc ions on the gating of the delayed potassium conductance of frog sartorius muscle. 1. A voltage-clamp method was used to examine the effects of zinc ions on the delayed potassium currents and also the slowly activating potassium currents that are turned on by depolarizing the membrane of frog sartorius muscle fibres. 2. In a control solution, the delayed potassium conductance had a maximum value of 17-8 +/- 2-5 mmho.cm-2. The reversal potential for the currents was -76-9 +/- 2-5 mV. The membrane potential where ninfinity had the value 0-5 was -49 mV. 3. The major effect of zinc ions was to slow the delayed potassium currents. The value of taun was increased approximately tenfold in 0-1 mM zinc. Zinc does not alter the effective valency of the gating particles of the potassium channel, but the conductance was shifted to more positive membrane potentials: in 0-1 mM zinc, the membrane potential where ninfinity had the value 0-5 was -32 mV. 4. Zinc ions, at a concentration of 0-1 mM, also reduced the maximum potassium conductance by about 60% to 7-3 +/- 0-8 mmho, cm-2; they did not alter the reversal potential of the currents, which had a value in 0-1 mM zinc of -74-6 +/- 1-5 mV. 5. Zinc ions had little or no effect on the rate of inactivation of the potassium currents. 6. Zinc ions had little effect on the conductance attributable to the slowly activating potassium system. In 0-01 mM zinc this conductance had a value at 0 to +10 mV of 1-25 +/- 0-29 mmho.cm-2. Zinc did not alter the reversal potential of the slow potassium currents from the value of -85 +/- 1-6 mV in the absence of zinc and had no effect on the time course of the turn-off of these currents at -60 mV. 7. The delayed potassium currents obtained in 0-002 and 0-01 mM zinc could not be fitted exactly with a simple fourth order equation, but were well fitted by a model proposing that zinc ions slow the opening and closing of the gating mechanism to one tenth the normal rate when they bind to the gating molecule. If the binding sites are not saturated, those gating molecules that do not bind zinc are assumed to be quite unaltered in their properties, though the potential dependence of their rate constants alphan and betan was assumed to be shifted to more positive levels. In one fibre in 0-01 mM zinc, the model fitted the currents best if 50% of the gating molecules bound zinc.


Circulating T and B lymphocytes in progressive systemic sclerosis. Thymus derived (T) and bone-marrow derived (B) lymphocytes were quantitated in 11 untreated patients with progressive systemic sclerosis (PSS) and in 11 age and sex matched controls. T and B lymphocytes were identified according to their receptor sites for sheep red blood cells and activated complement, respectively. All patients had a normal lymphocyte count. The mean per cent value of circulating T lymphocytes was less in PSS patients (38 per cent) as compared with controls (56 per cent) (P less than 0.005), while no significant difference existed for the circulating B lymphocytes (PSS 14 per cent; controls 11 per cent). The mitogenic response to phytohemagglutinin (PHA) was assessed by comparing dose response curves in PSS with those obtained from matched controls. No significant difference could be detected between these groups.


A genetic-epidemiologic study of chronic obstructive pulmonary disease. I. Study design and preliminary observations. Although certain environmental agents (e.g., cigarette smoking) are known to be causally related to chronic obstructive pulmonary disease (COPD), differential response to their deleterious effects suggests the importance of constitutional (host) factors. The voluminous literature on the familial occurrence of COPD as well as the association between genetically determined serum alpha 1-antitrypsin (alpha 1-at) deficiency and COPD, however, reveals many aspects yet to be clarified. Studies of alpha 1-at indicate that neither its nature nor its relationship to COPD is simple. Moreover, other familial factors are likely involved. To obtain a better understanding of the etiology and pathogenesis of COPD, both genetic and environmental factors are being examined in a multifaceted investigation. The preliminary observations are summarized. COPD patients have a higher frequency of Pi variant phenotypes than those without lung disease. Among other subjects, both cigarette smoking and Pi variant phenotypes are associated with increased pulmonary function abnormality. Finally, there is familial aggregation of pulmonary impairment that cannot be explained entirely by Pi type or smoking.


Surface markers of human lymphocytes.

Surface markers of human lymphocytes. The large accumulation of data on serum immunoglobulins (Igs) has made it possible to delineate readily the special membrane Ig receptors that respond to antigenic stimulation. B type lymphocytes are characterized by the selective presence of IgM and IgD. IgG, the main serum Ig, is rarely found and its previous reported presence was due to secondary adsorption. IgM and IgD occur together on the same lymphocytes and show similar or identical variable regions and antigen combining sites. The membrane Igs are positioned on the lymphocyte surface with a cosiderable part of the C-terminal portion of the heavy chains buried in the membrane. In addition to numerous other lymphocyte membrane markers, recent interest has centered on the new histocompatibility surface antigen, HL-B, which appears related to immune response genes and is selectively represented on B cells. Through the use of this group of lymphocyte markers considerable information on the character of the malignant cells in various leukemias and lymphomas has been obtained. Chronic lymphatic leukemia is essentially a proliferation of B cells. Acute lymphoblastic leukemia falls into two groups, a minor type that represents a proliferation of T cells and a major type that appears to show an immature cell type of probable B cells lineage. Various immunodeficiency syndromes have been clarified considerably through lymphocyte analyses and certain defects have been determined.