Characterization of extrachromosomal DNA in the flesh fly Sarcophaga bullata.

The polytene pupal foot pad cells of the flesh fly Sarcophaga bullata contain numerous extrachromosomal DNA containing granules. We have determined both the origin and the nature of the DNA sequences present in these granules. Studies done with quinacrine staining of seven day old pupal foot-pad polytene nuclei showed that the granules fluoresced very brightly while the chromosomal bands to which the granules were attached did not. The only other highly fluorescent regions of the polytene karyotype were the centromeric heterochromatin of chromosomes C and E and several bands associated with the nucleolus of Chromsome A. When polytene nuclei were hybridized in situ with cRNA made from highly repetitive DNA, many of the granules positively labeled. Most of the label on these slides was concentrated on the centromeric heterochromatin of chromosomes C and E. Quinacrine staining of the foot-pad cells at very early stages of pupal development showed that when granules were present, they were always closely associated with the same two centromeric regions, those of chromosomes C and E. Since the highly repetitive DNA located in these centromeric regions is underreplicated, we conclude that the granules result from an extrusion process which takes place early during the polytenization of these cells. The chromosomal integrity of the centromeric heterochromatin of chromosomes C and E is apparently disrupted and repetitive sequences are dissociated from the chromosomes as DNA granules which then secondarily become associated with chromosomal bands throughout the nucleus.


Lengths of transcribed rDNA repeating units in spermatocytes of Drosophila hydei: only genes without an intervening sequence are expressed.

In Drosophila hydei a 5 kb long intervening sequence (ivs) which is limited to only one of the three nucleolus organizers occurs in the 28S coding region of the rDNA (Kunz and Glätzer, 1979). This raises the possibility to study transcription of repeated genes with long intervening sequences. Three genotypes of males were studied each having only one defined nucleolus organizer. Spermatocytes of single males were spread in a solution of low salt and examined by electron microscopy. The length distributions of the repeating units, matrix units, and the apparent spacer units did not reveal two classes with a 5 kb length difference. The data suggest that in D. hydei the 5 kb long intervening sequence is not transcribed and that, in fact, the entire gene which contains an intervening sequence remains silent in primary spermatocytes. There is evidence that genes with an intervening sequence are not intermingled with "normal" genes at random.


Native and reconstituted chromosome fiber fragments.

The structure of hen erythrocyte chromatin fibers was studied with the electron microscope. Chromatin fiber fragments with a length of about 5,000 A and an average diameter of 320 A are composed of 13 globular subunits (superbeads) which contain different numbers of nucleosomes. Their number average corresponds to 17 nucleosomes. - The interaction of lysine-rich histones with nucleosome chains was investigated by reconstitution experiments and was found to be semi-cooperative.


Non-repetitive DNA sequence divergence in phylogenetically diploid and tetraploid teleostean species of the family cyprinidae and the order isospondyli.

Non-repetitive DNA of anciently tetraploid teleostean species was analysed for the presence of duplicated sequences. Closely related diploid species were investigated in comparison. From the reassociation kinetics of total nuclear DNA, rate constants and fraction sizes of classes of repetitive and non-repetitive sequences were determined. DNA fractions enriched in the slowest renaturing sequence class were determined. DNA fractions enriched in the slowest renaturing sequence class were prepared and subjected to reassociation. The rate constants of these reactions were compared with the values expected for single-copy DNA from analytical genome size determinations. From reassociated DNA enriched in non-repetitive sequences also the melting temperatures were determined as a measure of internal base sequence heterogeneity. It has been shown that the two ancient tetraploids Cyprinus carpio and Thymallus thymallus are, with regard to the thermal stability of reassociated non-repetitive DNA, and with regard to the correspondence of reaction rates with the values expected for single copy DNA, indistinguishable from diploid controls (Rutilus rutilus, Clupea harengus and Sprattus sprattus). The tetraploid species Salmo irideus, Salvelinus fontinalis and Coregonus lavaretus appear as very recent tetraploids with regard to these criteria. The significance of the results for estimating the time of occurrence of polyploidisation events in these taxa is discussed.


Contrasting DNA sequence organisation patterns in sauropsidian genomes.

The genomic DNA organisation patterns of four sauropsidian species, namely Python reticularis, Caiman crocodilus, Terrapene carolina triungius and Columba livia domestica were investigated by reassociation of short and long DNA fragments, by hyperchromicity measurements of reannealed fragments and by length estimations of S1-nuclease resistant repetitive duplexes. While the genomic DNA of the three reptilian species shows a short period interspersion pattern, the genome of the avian species is organised in a long period interspersion pattern apparently typical for birds. These findings are discussed in view of the close phylogenetic relationships of birds and reptiles, and also with regard to a possible relationship between the extent of sequence interspersion and genome size.


On the arrangement of chromosomes in the elongated sperm nuclei of Anura (Amphibia).

The position of specific constitutive heterochromatic chromosome regions within the elongated sperm nuclei of eight species of Anura was examined with Q- and C-banding. These species differ widely with regard to the number, size and position of the brightly fluorescing heterochromatic regions. The empirical frequency distributions determined for the heterochromatic regions relative to the longitudinal axis of the sperm nuclei were compared with random frequency distributions calculated on the basis of two spatial models. None of the specifically stained heterochromatic regions occupy any definite preferential position within the sperm nuclei. In two instances, a specific sequence of the heterochromatic regions within the sperm nuclei could be excluded. The type of chromosomal arrangement within the elongated sperm nuclei of Anura is discussed on the basis of the distribution patterns obtained.


Nucleolar relationships in some Australian chironomus species.

Members of a group of Australian Chironomus species in the pseudothummi complex show wide variation in number and location of nucleolar organizing regions (NORs). The structure of these regions has been examined by phase contrast microscopy and silver banding of salivary gland polytene chromosomes. Presence of nucleoli was also checked on other types of chromosomes in some species. The contribution of the silver banding technique to nucleolar studies in these chironomid chromosomes is discussed. Nucleoli often seem to emerge from groups of (up to 9) bands. Further studies are necessary to confirm the presence of rRNA cistrons in all of these bands. Banding differences, in particular absence of bands from homologous regions of some species which have smaller nucleoli or lack particular nucleoli, have been found. In the case of Ch. tepperi, however, little banding difference is apparent in the 16B region between the N(IV)+ and N(IV)- chromosomes, although in situ hybridization (Eigenbrod 1978) shows a deletion of rRNA cistrons in the N(IV)- stock. Differences in heterochromatin amount have also been observed at different NORs. A scheme for the evolution of nucleolar-producing regions in this Chironomus group in terms of these and other known chromosomal changes is presented and discussed.


Extracellular fluid volume and renal indices in essential hypertension.

Extracellular fluid volume (EFV), total blood volume (TBV), and renal indices were determined in 53 permanent essential hypertensive patients with normal renal function and balanced sodium intake and urinary output. In comparison with normal subjects, hypertensives had normal EFV values while TBV and the TBV/EFV ratio were significantly reduced (p less than 0.001). In hypertensives, a significant negative relationship (r = -0.40; p less than 0.005) was observed between the TBV/EFV ratio and diastolic arterial pressure. No correlation existed between TBV and diastolic pressure, whereas EFV (and also interstitial fluid volume) was positively related to diastolic arterial pressure (r = +0.41; p less than 0.005). Extracellular fluid volume and interstitial fluid volume were both directly correlated to the renal filtration fraction (r = +0.45; p less than 0.005). The study suggests that, in the disturbed partition of the extracellular fluid of hypertensives, changes in the interstitial space are involved and are related to variations in the renal indices.


Blood pressure and metabolic effects of 9-alpha-fluoro-hydrocortisone in sheep.

9 alphafluorohydrocortisone (9 alphaFF) is an analogue of hydrocortisone with both 'mineralocorticoid' and 'glucocorticoid' activity. 9 alphaFF was infused at 0.2, 0.63 and 2.0 mg/day for 5 days to intact conscious trained sheep. At high dose (0.63 and 2 mg/day) 9 alphaFF raises blood pressure in sheep, (mean arterial pressure rise 32 and 29 mm Hg respectively on the fifth day), lowers plasma [K], raises plasma [Na] and produces initial urinary sodium retention. At low dose (0.2 mg/day) blood pressure is raised (+16 mm Hg on day 5) but plasma and urinary electrolytes are unaltered. 9 alphaFF had no effect on water intake or urine output at any dose. In all animals withdrawal of 9 alphaFF was associated with a natriuresis. On the basis of its affinity for 'mineralocorticoid' and 'glucocorticoid' ovine renal receptors, 9 alphaFF at low dose may raise blood pressure by mechanisms not simply related to its 'glucocorticoid' and/or 'mineralocorticoid' action.


Comparison of the effects of 'glucocorticoid' and 'mineralocortocoid' infusions on blood pressure in sheep.

It is generally believed that adrenal steroid hypertension is due to the 'mineralocorticoid' and/or 'glucocorticoid' activities of the steroid(s). The present study examines the blood pressure and metabolic effects of steroid hormone infusion in intact conscious sheep to assess the relative contributions of 'glucocorticoid' and 'mineralocorticoid' activity. Cortisol at 5 mg/h increased mean arterial pressure (MAP) but the effect was small (MAP + 10 mm Hg on day 5). This rate of infusion produces blood cortisol levels appropriate for maximal ACTH stimulation. Cortisol at 20 mg/hr produced hypertension (MAP + 25 mm Hg on day 5, p less than 0.01) but also produced the 'mineralocorticoid' effect of severe hypokalaemia. Dexamethasone at 1 mg/hr produced small increases in MAP but a profound fall in plasma [K]. Aldosterone at 80 microgram/hr (a pharmacological rate) produced hypokalaemia, urinary Na retention but no effect on MAP over 5 days. Thus, in short term infusion experiments, 'mineralocorticoid' effects are not associated with hypertension. Pharmacological concentrations of predominantly 'gluc-corticoid' steroid hormones produced hypertension but also exhibited substantial 'mineralocorticoid' activity. At levels approximating maximal physiological secretion, the rise in blood pressure was small. These results supported the contention that ACTH induced hypertension in sheep represents a mechanism different from a simple 'mineralocorticoid' or 'glucocorticoid' action.


Achievement of standards for quality care of hypertension by physicians and nurses.

The quality of care provided by physicians and nurses to a hypertension clinic population was studied using retrospective chart audit to compare control of blood pressure (physiologic outcome) and provider performance (process). Data was collected from 200 records, 36.4% of patients, in the program. Return visits were kept by 173 patients (86.5%) during the 6 month study period. Satisfactory point prevelance BP control (diastolic less than or equal to 90 mmHg) was achieved in 103 (59.5%). Adequate process was documented for 49 of 69 patients with unsatisfactory BP control. The records of 20 patients (11.5%) did not satisfy minumum quality of care criteria. Physicians and nurses saw similar patient groups and did not differ in process documentation or outcome results. The audit methodology was efficient, effective in evaluating management and useful in providing information about staff performance.


Hypotensive and other cardiovascular effects of arachidonic acid in rabbits.

Intravenous administration of arachidonic acid lowers systemic arterial pressure in conscious and anesthetized rabbits. This hypotensive response does not show tachyphylaxis and is blocked by aspirin. The hypotension on i.v. administration is due to both a decrease in cardiac output and a decrease in systemic vascular resistance. The decrease in cardiac output is accompanied by a severe pulmonary hypertension and right ventricular failure. Upon i.a. arachidonic acid administration, the hypotension is due to a decrease in systemic vascular resistance. It is proposed that arachidonic acid is transformed predominantly into a vasoconstrictor metabolite in the pulmonary vascular bed and vasodilator metabolite in the systemic vascular bed. The nature of the metabolite remains to be established.


Effectiveness of psychotherapeutic counseling in methadone maintenance.

Therapeutic counseling has been widely adovacted with methadone maintenance, but its effectiveness has not been demonstrated. A review of the literature revealed a dearth of scientific investigations comparing treatment outcomes with and without counseling services. The few studies which have been reported seem to suggest that counseling does not significantly change treatment outcomes as measured by the usual indicators of illicit drug use, arrests, employment, and retention in the program. These studies suffered from a number of methodological flaws, however, including failure to adhere to research design, small sample size, poorly matched control groups, inadequate outcome criteria, and absence of post-treatment follow-up. Previous investigators have been nearly unanimous in calling for further studies of this issue. Since the cost of counseling services represents a major portion of treatment program budgets, there is an urgent need to document the effectiveness of these services with definitive studies.


Levo-alpha-acetylmethadol (LAAM) in the treatment of heroin addicts. I. Dosage schedule for induction and stabilization.

One hundred and seventy-nine patients who were dependent on street narcotics were inducted into LAAM. Ninety-two were inducted using a slow schedule: 20, 20, 30, 30, 40, 40, 50, 50, 60, 60, 70, 70, 75 mg on successive clinic visits (Mon., Wed., Fri.). Only 23% of the patients followed this schedule to 50 mg; 55% requested and received a faster induction. Eighty-seven patients were inducted using a rapid schedule: 20, 30, 40, 40, 50 mg. This schedule was acceptable to the majority of patients and caused no complaints of overdosing. We suggest that this schedule be used in clinics where patients who have been shown to be dependent are inducted directly onto LAAM.


Barbiturate tolerance and hypersensitivity of arterial smooth muscle.

Experiments were undertaken on rats chronically treated with pentobarbital sodium, 50 mg/kg three times per day for a period of five days, to determine whether excised aortic or venous (portal vein) smooth muscle would demonstrate any change in reactivity to catecholamines or potassium chloride. Although sleeping time was reduced 50% (indicative of tolerance to the barbiturate), mean arterial blood pressure was not affected. Aortic strips, but not portal veins, excised from barbiturate-treated animals exhibited hypersensitivity to both contractile stimulants. Potassium-depolarized calcium-depleted aortic tissue, but not portal venous smooth muscle, from the barbiturate-treated animals contracted to lower concentrations of Ca2+ than did the arterial smooth muscle from the saline-treated control rats. The present observations thus indicate that chronic barbiturate treatment in rats can induce drug supersensitivity of excitable tissue other than one associated with the central nervous system. Our results on arterial smooth muscle could help to shed light on the unexplained rises in arterial blood pressure observed in humans undergoing barbiturate withdrawal.


Alcoholic women treated by behaviorally orientated therapy: an 18-month follow-up study.

Follow-up results of a behaviorally orientated treatment program for alcoholic women are presented. Sixty patients, carefully screened, were admitted on a special ward in groups of not larger than 12 for a period of 3 months. Abstinence was the declared goal of all individual and group treatments. More than 13 months after discharge interviews were carried out with 58 of the 60 former patients in their homes. Further information was collected from relatives and social workers. Forty per cent of those interviewed qualified as abstinent, 9% had improved, 3% were controlled drinkers, 5% had become worse and 43% had not improved. Specific aspects of the program are discussed.


The mechanism of rosette formation between sheep red blood cells and L-A9 fibroblasts.

More than 20% of mouse L-A9 fibroblasts from rosettes with sheep red blood cells. This relatively weak interaction is mediated by receptors of glycoprotein nature; species-specific antigens of SRBC are part of, or lie in close proximity to, this binding. SRBC receptors are present on most L-A9 fibroblasts, neither Con A receptors nor MHL products are part of the SRBC receptors. However, Con A- and H-2 antibody-induced alterations in the membrane and cytoskeletal system accompanying cap formation produce a strong inhibition of rosette formation. This inhibition may be due to an interference into the adhesion by involving the cytoskeletal system in the redistribution processes because the same effect was obtained with Colcemid and cytochalasin B.


A spontaneous chicken chimaera with serologically and morphologically different types of erythrocytes.

Among hybrids of the inbred chicken lines, cock 1357 was found to be chimaeric in red blood cells. This cock possessed three serologically distinct types of erythrocytes and two types different in shape and size.


Isolation of human germ-line DNA suitable for recombinant DNA studies.

Dna from human sperm cells can be isolated with size and purity sufficient for use in recombinant DNA research. The DNA averages 100 000 base pairs (bp) in size (about 70.10(6) daltons) and is free of somatic cell, bacterial, and viral DNA. It can therefore be cloned under P2 + EK2 conditions as stipulated in the 1978 NIH Guidelines for recombinant DNA research.


Asymmetric linker molecules for recombinant DNA constructions.

Asymmetric EcoRI DNA linkers consisting of an AATTC(A)7 dodecamer and a complementary G(T)7 octamer were synthesized. Ligation of such linkers to DNA fragments obviates the need for EcoRI digestion prior to cloning in EcoRI-cleaved vectors.


Effect of portasystemic venous shunt surgery on hyperglucagonaemia in cirrhosis: paired studies of pre- and post-shunted subjects.

The effect of liver disease on glucagon metabolism was examined in nine patients with chronic liver disease who were studied both before and after the creation of a surgical portasystemic shunt. Hepatocellular function did not deteriorate after shunt surgery. However, hepatic perfusion with splanchnic venous blood, as determined by scintisplenoportography, decreased after shunt surgery in six subjects but appeared unaltered in three. Basal plasma immunoreactive glucagon (IRG) levels in the pre-shunt cirrhotic group were significantly greater (p <0.005) than in control subjects and further increased (p <0.05) after shunt surgery. Moreover, the increase in basal IRG after shunt was evident only in patients in whom portasystemic shunting was demonstrably increased by surgery. Despite the higher basal IRG levels postoperatively, shunt surgery in the cirrhotics did not alter basal glucose and insulin levels or the glucose and insulin response to a glucose or protein load. Circulating IRG was heterogeneous in the pre-shunt cirrhotic patients: the 9000 molecular weight fraction comprised 27+/-4%, the 3500 mol. wt. fraction 71+/-4%, and the > 40 000 mol. wt. fraction was minimal. After shunt surgery, the relative proportion of the 9000 mol. wt. fraction of IRG (13+/-3%) decreased significantly (p <0.05) and this fall was associated with a corresponding increase in the 3,500 mol. wt. fraction (84+/-4%). It is concluded that, in cirrhosis, hyperglucagonaemia is: (1) dependent on the degree of portasystemic shunting rather than impaired hepatocellular function; (2) predominantly due to increased circulating 3500 molecular weight glucagon; and (3) not a major factor in the pathogenesis of carbohydrate intolerance in liver disease.


Suppressive effect of alcoholic liver disease sera on lymphocyte transformation.

The effect of alcoholic patient sera on in vitro lymphocyte transformation was studied using mitogen-induced uptake of (3)H-thymidine to measure blastogenesis. With pokeweed mitogen as the stimulus, transformation of normal lymphocytes in sera of alcoholics with either normal or fatty livers was not significantly different from that obtained in pooled human serum (PHS). However, in sera of patients with either alcoholic hepatitis or inactive cirrhosis mean transformation was significantly reduced (P <0.001, <0.02 respectively). With phytohaemagglutinin-P or concanavalin A as mitogens, suppression of transformation was not as marked but followed the same pattern. A significant negative correlation was observed between the magnitude of transformation and serum bilirubin and aspartate aminotransferase levels. An intra-patient comparison of the effects on transformation of normal lymphocytes by simultaneously collected peripheral and portal venous sera, and of peripheral sera obtained before and after portasystemic shunt surgery, indicated that the factor(s) responsible did not originate in the splanchnic circulation nor did it accumulate in the serum because of failed hepatic clearance. By performing transformation experiments in the presence of inhibitory patient sera diluted with PHS it was possible to show that these sera caused true inhibition of transformation rather than suppression due to failure to sustain cell culture because of nutritional deficiencies. Inhibitory sera did not contain high levels of the enzyme thymidine phosphorylase and did not significantly inhibit binding of (125)I-labelled mitogens to the lymphocyte surface. These findings indicate that the inhibitory effect of sera from alcoholics is of potential in vivo importance, that the effect increases with the degree of heptocyte damage, and that it is unrelated to the nonhepatic metabolic affects of chronic alcoholism.


Gilbert's syndrome: evidence of morphological heterogeneity.

Hepatic ultrastructure was examined by electron microscopy in 25 patients with Gilbert's syndrome and the changes in the smooth endoplasmic reticulum quantified by grid technique. Thirteen patients showed gross hypertrophy of the smooth endoplasmic reticulum (SER). These were designated Gilbert's EM Positive. The remaining 12, designated Gilbert's EM Negative, did not differ significantly from normal controls. The EM Positive group showed a significantly greater percentage response to caloric restriction (P less than 0.01) and an exaggerated response to nicotinic acid stimulation when compared with the EM Negative group and normal controls. These results suggest that SER hypertrophy is not, as previously suggested, a constant feature of Gilbert's syndrome but rather a characteristic of a distinct subpopulation.


Serum lysozyme levels in malignant histiocytosis of the intestine.

Serum lysozyme levels were significantly raised in a group of eight patients with malabsorption associated with gastrointestinal lymphomas of a type recently characterised as malignant histiocytosis of the intestine. In four of the cases, levels were markedly raised. In contrast there was no significant difference between groups of patients with uncomplicated adult coeliac disease and healthy controls. The estimation of serum lysozyme is a simple test to perform and may be valuable in the diagnosis of malignant histiocytosis of the intestine, in particular differentiating it from uncomplicated adult coeliac disease.


Enhancement of ileal adaptation by prednisolone after proximal small bowel resection in the rat.

The effect of prednisolone on the adapted ileum of the rat after jejunal resection was examined. Three weeks after 50% proximal small bowel resection animals were fed pharmacological doses of soluble prednisolone (0.75 mg/kg/day) over a one week period, and killed at four weeks. Animals treated with prednisolone showed significant increases in brush border alpha-glucosidase, leucyl-2-napththylamidase and gamma-glutamyl transferase (P less than 0.01) per unit length of intestine compared with resection alone and transection reanastomosis control groups. This increase was the result of a significant enhancement (P less than 0.01) of brush border digestive enzyme activity per milligram of epithelial cell DNA-that is, per enterocyte-and was associated with a similar increase in enterocyte RNA content. In contrast, the activities of lysosomal and mitochondrial marker enzymes per milligran of DNA were similar in each group. Cell proliferation was not further stimulated by prednisolone. Thus prednisolone can selectively enhance brush border digestive capacity after intestinal resection without increasing cell proliferation. The increase in enterocyte RNA suggests that enzyme induction may be the mechanism of this effect.


Enkephalins in large bowel malignancy and in acute appendicitis.

Leucine and methionine enkephalins were measured by biological assay in normal colon, adenocarcinoma of the colon, carcinoma of the caecum, and in normal and inflamed appendix. Methionine enkephalin levels in both the adenocarcinomas and inflamed appendices were significantly higher than in normal controls. No significant change occurred in leucine enkephalin levels. The caecal tumours were anaplastic and contained no demonstrable opioid activity.


Survival and the immune response in patients with carcinoma of the colorectum.

One hundred and seven patients with colorectal carcinoma were examined for their immune response to autologous tumour. Patient leucocyte migration inhibition by tumour antigen, migration inhibition of normal subject's leucocytes by patient's serum, and the assessment of lymphocyte invasion of the tumour specimen were used to measure the immune response. Forty-one and 51% of patients were immune by leucocyte migration inhibition and tumour invasion by lymphocytes respectively. The immune patients had a survival advantage at three years on Chi-squared analysis. Patients whose serum contained a factor that inhibited the migration of leucocytes obtained from normal individuals had a diminished survival prognosis. The donors of these sera had a 50% chance of dying or of developing recurrent disease. These same individuals represented 30% of all those tested by this method. The immune patients included the sera donors as a subgroup 30% of all those tested by this method. The immune patients included the sera donors as a subgroup who, if excluded from the life table analysis, left a group of immune subjects who had very superior survival features.


Trypsinogen variants in pancreatic juice of healthy volunteers, chronic alcoholics, and patients with pancreatitis and cancer of the pancreas.

Polyacrylamide gel electrophoresis of pure pancreatic juice from 14 healthy normal subjects, 11 chronic alcoholics without detectable pancreatic disease, 15 patients with pancreatitis, and two with cancer of the pancreas consistently demonstrated the presence of two variants of trypsinogen with different electrophoretic mobilities. In healthy normal subjects the proportion of cationic to anionic trypsinogen was invariably greater than 1 and averaged about 2. In chronic alcoholics, patients with pancreatitis or cancer of the pancreas, this ratio, with a single exception, was below one and averaged about 0.45. The extraordinary consistency of these findings suggests that the quantitative relationship between cationic and anionic trypsinogen in human pancreatic juice may be a very sensitive indicator of incipient or existing pancreatic pathology. The most acceptable explanation for the reversal of the normal zymogen ratio in pancreatic disease is a selective increase in the synthesis of the anionic variant relative to that of the cationic species. Total trypsinogen concentrations differed widely from one another in the three patient groups, but the ratio of cationic to anionic trypsinogen exhibited little change and remained below 1. Our results also demonstrate for the first time a specific effect of chronic alcohol abuse on the secretory profile of a pancreatic enzyme in human subjects. A newly discovered minor, trypsinogen-like component of human pancreatic juice was found to be significantly increased in pancreatic juice of chronic alcoholics, decreased in pancreatic secretions of patients with pancreatitis, and barely detectable in those of two patients with cancer of the pancreas.


Blastomycosis of the colon resembling clinically ulcerative colitis.

An 8 year old Brazilian girl had an infection, apparently confined to the large intestine, with Paracoccidioides brasiliensis. The symptoms were diarrhoea with fresh blood and mucus, severe malnutrition, and a spastic and ulcerated colon. She is making good progress on co-trimoxazole.


Mitochondrial glutamic oxaloacetic transaminase and its clinical significance.

The m-GOT were studied in 57 patients with liver diseases, diagnosed by peritoneoscopy and biopsy. In acute hepatitis, the m-GOT rose to 100 units or there-about. But in chronic hepatitis, even in hepatitis B with sublobular necrosis, the m-GOT were low and 20--30 units. On the other hand, in alcoholic hepatitis, the m-GOT were 50--60 units which may be considered to be higher than expected for comparable their histological necrotic findings. These values were higher than OCT, which were measured at the same time. This results showed that there might be m-GOT induction by alcohol. In liver cirrhosis lower values were obtained. Generally m-GOT was liable to be lower as the lobular distortion was getting severer.


Critique of concepts and therapy in the action language approach to psychoanalysis.

Critical evaluation is made of the attempts to reformulate basic psychoanalytic concepts in terms of a theory of action language. The criticism focuses on issues of the scientific status of psychoanalytic knowledge, the role of experience as the basis of psychoanalytic knowledge, the role of metaphor in the formulation of psychoanalytic theory (focusing particularly on the issue of anthropomorphism and the forms of acceptable metaphor in the theory), and the problem of levels of abstraction in theoretical conceptualization. Particular issues in the action language approach, which are challenged from a more traditional process-oriented psychoanalytic perspective, are the notion of action; the status of mind; the specific formulations and conceptualizations of drives and motives, conflicts, resistance, affects, and internalization; the nature of the concepts of self and identity. The critique developed in these areas is then utilized as the basis for assessment of clinical implications, particularly their application in specific psychoanalytic contexts.


Efficacy in infancy: a review of some experimental studies and their possible implications for clinical theory.

I have reviewed some experimental studies which deal with the issue of the infant's control over environmental events, the infant's joy when it discovers that an external event is contingent upon its activity, and the corresponding trauma of being unable to influence, predict or comprehend an event which the infant expected on the basis of previous experience to be able to control or understand. This joy in being a cause seems a clear expression of what White called effectance pleasure. I regard the sense of efficacy as the core of the developing sense of self and traumatic disturbances in the sense of efficacy as core narcissistic injuries which predispose to significant psychopathology in the course of development.


Fathering: a review of some psychoanalytic contributions on paternity.

The paper has traced psychoanalysis' gradual appreciation of a father's facilitative impact on his children's psychosexual and psychosocial growth. Freud's initial notions accentuated the inhibiting, punitive aspects of the paternal representation, highlighting, as they did, the oedipal father of the primal horde. Save for a few significant glimmers here and there, he pretty much failed to consider a son's or daughter's search for a father with whom to identify and, with this, underplayed some of the crucial preconditions for the oedipal complex itself. In recent years, an ego-psychological focus on the 'dual unity' of mother and child, in Mahler's words, has tended to relegate the father to a secondary role in pre-oedipal development. And yet, influenced by this overview, Loewald, Greenacre, Abelin and others have underlined the ways in which a father helps extricate a child from the maternal orbit, facilitating a sense of reality, self-constancy, sexual identify and other epigenetic achievements which help secure object constancy and self-identity. What remains is a fuller elucidation of the reciprocal and complex affective interchanges that take place within the father-child dyad throughout childhood.


Remarks on transference-countertransference in psychotic states.

Clinical material of patients in psychotic states indicates that in those states the transference is directed into the therapist's body. The emotional experience thus created in the therapist, which is usually called countertransference in its broad meaning, should rather be seen as very early forms of object relationships. The complexities of the above easily influence the analyst in her role of interpreter. Therefore in the actual work with these patients the verbal interpretation, which represents an elaboration of the transference, in the author's view should be seen as countertransference.


The developmental approach to 'working through' in the analytic process.

The developmental orientation and approach has been utilized in this paper as a paradigm to understand some of the phenomena of working through in the analytic process. A case is presented of a patient who was arrested along several developmental lines and had suffered from a wool fetish. Many changes in the working through process could be attributed not only to meliorative effects of interpretation but to developmental progression as well. Furthermore, this developmental progression occurred within the analysis not only in relation to the analyst's interpretations but to the developmental impact on the patient of experience with the analyst and with significant others. The patient attained increasing capacities to utilize insight in actions that themselves led to new experience of developmental import, and in a spiral process, further structural developmental change was achieved which consolidated its dominance through further capacity for new insights.


Stage fright.

Stage fright is a universal human experience that occurs with varying intensity in everyone who stands before an audience. The anxiety generated in this situation stems from the re-emergence of certain key developmental experiences. The dynamics involved are related both to genital and to pre-genital conflicts. Shame arises from conflicts around exhibitionism, from concerns over genital inadequacy, and from the fear of loss of control. Guilt is produced from the aggression inherent in self-display and from the fear of the destruction of one's rivals, along with the dread of retaliation. A major portion of the stage fright reaction is the reactivation of the crisis of separation-individuation, which generates separation anxiety connected to the fear that asserting oneself as a separate individual will result in withdrawal of love and admiration by maternal figures, i.e. the audience. The various developmental experiences are differentially weighted in each individual's stage fright reaction depending on the vicissitudes of his early childhood experience. Perhaps it is fortunate that few performers ever completely master stage fright, for an intangible sense of communion between the performer and his audience might well be lost as a by-product of the mastery.


Effects of physical training on cardiovascular function following myocardial infarction.

Three to twelve (7.1 +/- 3.2) months after myocardial infarction, subjects under 54 (45.0 +/- 4.7) yr were assigned randomly to high-intensity (HIE, n = 37) or low-intensity (LIE, n = 42) exercise programs. Cardiac outputs (Q) during graded bicycle ergometer exercise were measured by a CO2-rebreathing method on entry and after 6 and 12 mo of training. The initial exercise Q was low in relation to work load, due to a low stroke volume (SV). Over the year of training, the predicted maximal O2 intake of the HIE group increased significantly (from 26.0 to 30.3 ml.kg-1.min-1), while that of the LIE group showed no significant alteration. During the first 6 mo, the heart rate of the HIE group was significantly reduced at each work level. There was an associated widening of arteriovenous oxygen difference, but SV was unchanged. These findings were attributed to extracardiac factors, including a redistribution of blood flow, biochemical changes in the trained muscle, and a secondary reduction of sympathetic drive. Over the second 6 mo, the SV of the HIE group increased 10%; this may reflect an increase of intrinsic myocardial contractility that develops if high-intensity training is sustained. The LIE group showed no major changes of cardiovascular function over the year of observation.


Mechanisms of increased maximum expiratory flow during HeO2 breathing in dogs.

We used the retrograde-catheter technique to investigate the effect of a helium-oxygen gas mixture (HeO2) on resistance to maximum expiratory flow (Vmax) in airways subsegments between alveoli and the equal pressure point (EPP), and between EPP and the flow-limiting segment (FLS). FLS were found at the same site in main-stem bronchi on both air and HeO2 in most dogs studied. Static elastic recoil pressure (Pel = 7 +/- 1 cmH2O) and the lateral pressure at FLS (Ptm' = 11 +/- cmH2O) were not different on the two gases, and delta Vmax averaged 33 +/- 12%. EPP were located on HeO2 in segmental bronchi (7 +/- 2 mm ID), and EPP on air were always located more downstream. There was no density dependence of resistance between alveoli and EPP on HeO2, and delta Vmax was due to the marked density dependence of the pressure losses of convective acceleration in the short airway segment between EPP HeO2 and FLS. Assuming that FLS is the "choke point," these findings are consistent with wave-speed theory of flow limitation modified to account for viscous pressure losses in peripheral airways. These results and conclusions question previous interpretations of delta Vmax as an index of peripheral airways obstruction, and demonstrate the utility of wave-speed theory in explaining complicated mechanisms of expiratory flow limitation.


Cardiopulmonary readjustments in passive tilt.

There is ample evidence that posture affects many cardiorespiratory variables, but the extent to which secondary reflex mechanisms complement or oppose the primary gravity effect is not clear. We have addressed ourselves to this problem by studying five normal volunteers, passively tilted from the supine to the upright position in 15 degrees increments, in random sequence, determinging cardiac output (Q), heart rate (HR), stroke volume (SV), minute and alveolar ventilation (VE and VA), functional residual capacity (FRC), and arterial-end-tidal PCO2 pressure difference. In each position, four to five measurements were obtained by noninvasive techniques. Changes in Q and in FRC were linearly related to the sine of the tilt angle, indicating that reflexes were either absent or that their net effect was proportional to the effects of gravity; this was clearly not the case for other variables (HR, SV, VE, VA) in which it was possible to demonstrate threshold values for the appearance of secondary changes.


Effects of glycogen depletion and work load on postexercise O2 consumption and blood lactate.

To study a possible relationship between blood lactate and O2 consumption (VO2) after exercise, 11 male subjects exercised on a bicycle ergometer at moderate and heavy work loads in both normal glycogen and glycogen-depleted states. At rest, glycogen depletion resulted in significantly lowered blood glucose and lactate concentrations, CO2 production (VCO2), respiratory exchange ratio (R), and minute ventilation (VE). With the exception of glucose, these variables changed more in response to heavy exercise (HE: 2 min at a mean of 1,750 kg.m/min) than to moderate exercise (ME: 2 min at a mean of 1,000 kg.m/min). At either work load, VCO2, R, and lactate showed consistently greater responses in the normal glycogen state. The slope of the initial component of the postexercise VO2 curve was unaffected by either work load or lactate. Although the slope of the slow component of the postexercise VO2 curve became significantly more negative after HE, it was unaffected by the level of lactate. These results are inconsistent with the hypothesis of a "lactacid O2 debt." Exercise intensity was the predominant factor influencing the magnitude and kinetics of postexercise VO2. Glycogen depletion resulted in lower VCO2, R, and blood lactate, but higher VE during heavy exercise. The results suggest that factors, in addition to CO2 flux to the lungs, influence VE during exercise.


Responses of conscious rabbits to CO2 at ambient temperatures of 5, 20, and 35 degrees C.

Conscious rabbits were exposed to atmospheric air or to 6% CO2 in air at ambient temperatures (Ta) of 5, 20 and 35 degrees C. Measurements were made of rectal temperature (Tre), metabolic rate (MR), respiratory frequency (f), tidal volume (VT), and minute volume (VE). CO2 exposure did not affect Tre at any Ta and only affected MR at 35 degrees C when it caused an increase. At each Ta hypercapnia caused an increase in VT and a decrease in f. At 5 degrees C VE was increased by CO2, at 35 degrees C VE decreased, and at 20 degrees C the results were variable. The data were examined in the light of theories relating to the relative contributions of inputs from brain stem and from pulmonary stretch receptors, in response to body temperature and CO2 partial pressure. It was concluded that hypercapnia stimulates an increase in VT via the brain stem, whereas at the same time removing a hypocapnic drive which, along with central thermal inputs, stimulates f.


Generation and regulation of breathing in utero: fetal CO2 response test.

Breathing responses to increasing fetal arterial CO2 pressure (PaCO2) were measured in 15 mature fetal lambs in utero during hyperoxic CO2 rebreathing in the ewe. Fetal breathing was expressed as 1) respiratory drive (RD), i.e., the early slope of intratracheal pressure during inspiration, and 2) ventilation equivalent (VEq), i.e., the product of intratracheal pressure and frequency of breathing. RD and VEq increased linearly with increasing PaCO2. CO2 threshold beyond which apneic fetuses started breathing was higher than the extrapolated CO2 threshold in spontaneously breathing fetuses. Afferent sciatic nerve stimulation, which induced regular breathing in apneic fetuses, lowered their CO2 threshold but did not alter their sensitivity to CO2. Naloxone resulted in initiation of fetal breathing, decreased CO2 threshold, and increased sensitivity to CO2. These studies demonstrate that respiratory center responsivity can be quantified in the lamb fetus in utero, that nonspecific somatic stimulation lowers fetal breathing threshold to CO2, and that endogenous opioid peptides could participate in the physiological suppression of breathing in fetal life.


Lung inflation and longitudinal distribution of pulmonary vascular resistance during hypoxia.

Using the low-viscosity bolus method, we examined the influence of lung inflation on the longitudinal distribution of vascular resistance during hypoxia in isolated cat lungs. During hypoxia, increasing transpulmonary pressure decreased vascular resistance but did not change the volume into the lung at which the maximum local resistance was located. This was in contrast to the normoxic situation in which inflation caused an increase in resistance over much of the transpulmonary pressure range studied and moved the maximum local resistance downstream. These results indicate that during hypoxia the major increase in resistance was in extra-alveolar vessels and that distension of these vessels by lung inflation decreased the magnitude of the pressor response. The increase in resistance in alveolar vessels, which occurred on inflation, was similar during control and hypoxic conditions but was a smaller part of the total resistance during hypoxia because of the much larger extra-alveolar vessel resistance.


The lung as a filter for microbubbles.

A new ultrasonic Doppler device has been used noninvasively over the femoral artery of anesthetized dogs to prove that it can detect carefully calibrated microbubbles of 14--189 micrometers diam when these are infused directly into the aorta. The same evaluated technique has then been employed to detect any bubbles escaping into the arterial system when gas was infused into the venous system either as microbubbles or as a bolus. Results from 18 dogs showed that, under normal conditions, the lungs are a superb filter for bubbles and that any cutoff diameter is less than 22 micrometers. However, bubbles escaped entrapment when the lungs were severely overloaded with gas (20 ml) or were pretreated with a pulmonary vasodilator (aminophylline). The dog preparation and arterial Doppler device appear to be ideal for future studies to determine what other factors might compromise the capability of the lungs to filter microbubbles. Physiological parameters showed dramatic changes when bubbles were detected as escaping into the arterial system by comparison with their effect when retained within the lungs. Changes in respiration profile indicated that they may offer a useful index of the degree of venous embolization and, hence, a warning of impending overload leading to arterial embolization.


Growth of hygroscopic aerosols in a model of bronchial airways.

Experiments have been performed on the "breathing" of micron-size hygroscopic aerosols in and out of a four-generation model of the bronchial tree. Comparison of the experimental results on aerosol growth in the model with the classical theory for dilute aqueous solutions of nonpolar salts shows a) that the theory is applicable to conditions in the airways, b) that to a high degree of approximation the process represents deposition followed by growth, and c) that there is a significant amount of trapping of particles near their equilibrium size in the deeper model tubes. These experiments are the first to verify that the classical particle growth theory is applicable to the particle sizes and environmental conditions present in the human airways during hygroscopic aerosol therapy. This theory will be useful in designing an optimal hygroscopic aerosol delivery system, but several questions including the method of generation and the effect of drug solutions on particle equilibriums remain to be answered.


Fractionating respiratory resistance in young children.

Total respiratory resistance (Rrs) and the fraction of this resistance located peripherally, (Fp) were measured in a group of children (3--5 yr old). The technique used forced random noise to characterize the frequency dependence of effective resistance and an algorithm to compute Rrs and Fp from these data. The overall mean value +/- SD for Fp was 0.534 +/- 0.070; the mean value of 0.464 for the six children near 5 yr of age was significantly different (P less than 0.001) from the mean value of 0.576 found in the younger children. The overall mean value +/- SD for Rrs was 16.9 +/- 5.8 cmH2O.l-1.s; individual values appeared to be correlated with height. These results agree with previous reports indicating that children have a larger fraction of respiratory resistance in the periphery than do adults.


Site of pulmonary edema after unilateral microembolization.

The effect of unilateral pulmonary microembolization on regional lung extravascular fluid accumulation was determined in dogs. Embolization was produced by injecting 100-micrometer-diam glass beads (0.25 g/kg) into the right pulmonary artery. After embolization of one lung, pulmonary arterial pressure (Ppa) and pulmonary vascular resistance increased (P less than 0.05) from base-line values of 11.7 +/- 1.3 to 17.9 +/- 1.3 Torr and of 3.4 +/- 0.5 to 5.5 +/- 0.5 Torr/(1/min). Blood flow to embolized lung measured with labeled microspheres decreased from 104.2 +/- 24.9 to 35.2 +/- 9.2 ml/min.g bloodless lung after embolization, whereas flow to the normal lung increased from 43.1 +/- 5.6 to 71.2 +/- 19.2 ml/min.g bloodless lung. Extravascular lung water-to-bloodless dry lung weight ratio (W/D) of 4.97 +/- 0.32 was greater (P less than 0.001) in the embolized lung than the value of 3.34 +/- 0.15 in nonembolized lung. In six dogs pretreated with 500 U/kg of heparin, a similar degree of duration of embolization and similar hemodynamic changes did not result in significant differences in W/D (3.88 +/- 0.18 in right lung vs. 3.02 +/- 0.53 in the left lung), and the right lung ratio was less (P less than 0.05) than the value in the heparinized dogs, suggesting that humoral mechanisms contribute to the genesis of pulmonary edema after regional embolization. Therefore, unilateral embolization leads to a greater increase in extravascular content in the embolized lung than in the nonembolized lung. Because Ppa was in the normal range after embolization, regional pulmonary edema may be due partly to the local release of factors that increase lung vascular permeability.


Action potentials in single axons: effects of hyperbaric air and hydrostatic pressure.

Resting potential and action potential parameters of crayfish (Procambarus acutus) single axon were examined under hyperbaric air and hydrostatic pressure to 8.6 atmospheres absolute to determine if evidence for the basis of neurological dysfunctions that may occur in diving in this pressure range is detectable at the membrane level. Hyperbaric air increased the maximum rates of depolarization and repolarization of the action potential by (2.2 +/- 0.2) and (2.1 +/- 0.2)%/atm, respectively. Hydrostatic pressure had an opposite effect, decreasing the maximum rates of depolarization and repolarization by (0.57 +/- 0.13) and (0.9 +/- 0.3)%/atm, respectively. Action potential duration was decreased (0.91 +/- 0.19)%/atm by hyperbaric air. Action potential amplitude, resting potential, and threshold were unchanged by increasing pressure. Increasing the nitrogen tension alone produced results consistent with hyperbaric air compression. Thus, increased hydrostatic and nitrogen pressures oppositely affect the rates of polarization of the action potential in a reversible manner at pressures in the range encountered by human divers.


Endotoxin protection against oxygen-induced acute and chronic lung injury.

Small dosages of endotoxin (100--500 micrograms/kg) provide significant protection against the acute manifestations of pulmonary O2 toxicity and lethality. Ninety-seven percent of endotoxin-treated adult rats survived a 72-h exposure to greater than or equal to 95% O2 with mimimal lung changes, compared to 32% of control animals (P less than 0.01). Exposure to greater than or equal to 95% O2 for 7 days resulted in a 20% survival rate in untreated control rats vs. 98% survival in endotoxin-treated rats (P LESS THan 0.01). Histological evaluation of lung from survivors revealed substantially less collagen and reticular fiber deposition in the endotoxin-treated animal lungs. Endotoxin treatment was associated with increased activity of the protectant antioxidant enzyme systems of the lung in an apparent dose-response manner. Endotoxin's protective activity against O2 toxicity does not appear to depend on an initial toxic insult to the lung like with alpha-naphthylthiourea, oleic acid, or alloxan treatment. The data support a protective role for endotoxin against the acute and the more chronic manifestations of O2-induced pulmonary injury.


Effects of normal and loaded spontaneous inspiration on cardiovascular function.

To assess the hemodynamic effects of spontaneous inspiration, we studied 12 anesthetized mongrel dogs during normal and loaded inspiration, before and after bilateral cervical vagotomy. Peak aortic flow fell (15--20%) whereas peak pulmonary artery flow rose (15--20%) under all conditions. When aortic flow fell, left ventricular diastolic size decreased whereas aortic and left atrial transmural pressures increased slightly. Right ventricular diastolic size and right atrial transmural pressure increased. During inspiratory loading transmural pressures rose more, but the fall in aortic flow remained the same. After vagotomy, inspiration was prolonged, allowing aortic flow to return to preinspiratory levels. At this time left ventricular diastolic size was increased compared to preinspiratory levels and there were further increases in left atrial and aortic transmural pressures. We have concluded that at least two factors affect aortic flow during inspiration: 1) a decrease in left ventricular preload that is associated with decreased left ventricular compliance, and 2) increased impedance to left ventricular emptying as reflected by the increase in aortic transmural pressure. This may play a greater role during inspiratory loading and when inspiration is prolonged.


Role of skin temperature in the control of sweating.

In five male subjects tympanic membrane temperature (Tty), rectal temperature, skin temperatures at 12 sites were simultaneously recorded. Local sweating rate was measured at six sites using resistance hygrometry. After steady-state sweating was established, the lower body was heated at ambient temperatures of 50, 60, 70, and 80 degrees C or cooled at an ambient temperature of 29 degrees C while the upper body remained at a constant ambient temperature. During lower body heating or cooling, Tty was maintained constant by the drinking of cold (10 degrees C) or warm (45 degrees C) water. Sweating rate on both upper and lower body surfaces was proportional to lower body skin temperature. The regression coefficients for sweating rate versus mean lower body skin temperature varied from 0.03 to 0.09 mg/cm2.min. degrees C between subjects, but were not significantly different from each other (P greater than 0.05). This study demonstrates an influence of cutaneous thermoreceptors on sweating rate under steady-state conditions.


Interdependence of Na+ and Cl- transport in dog tracheal epithelium.

Previous studies showed active transport of Cl- toward and of Na+ away from the luminal surface of dog tracheal epithelium. The possible interdependence of Cl- and Na+ fluxes has not been explored fully in this preparation. The purpose of the present study is to investigate the relationship between these fluxes. Substituting choline for Na+ in the media bathing dogs tracheal epithelium reduced net Cl- transport toward the lumen from 1.86 +/- SE 0.27 to 0.49 +/- SE 0.20 mueq.cm-2.h-1. Substituting SO4(2-) For Cl- decreased net Na+ flux toward the lumen from -1.05 +/- SE 0.20 to -1.78 +/- SE 0.36 mueq.cm-2.h-1. Acetylcholine (5 x 10(-4) M) and terbutaline (10(-5) M) increased and furosemide (10(-3) M) decreased net Cl- transport toward the lumen in control, but not in Na+ free bathing media. Acetylcholine increased net Na+ flux toward the lumen in control, but not in Cl- free bathing media. Thus this study showed that 1) in media lacking Na+, net Cl- flux toward the lumen is decreased, and vice versa, 2) the increases in Cl- transport toward the lumen due to acetylcholine and terbutaline and the decrease due to furosemide required Na+ and 3) in the increase in Na+ flux toward the lumen due to acetylcholine required Cl-. These findings indicate that there is an interdependence of Cl- and Na+ fluxes in dog tracheal epithelium.


Modification of cardiac function by synchronized oscillating acceleration.

The sensitivity of selected cardiovascular (CV) responses to the physical stressor of External whole-body oscillating Acceleration Synchronized with the Electrocardiogram (EASE) was analyzed in 8 chronically instrumented tranquilized dogs. A sinusoidal acceleration wave form was imposed on the supine animals along the spinal (+/- Gz) axis at a constant amplitude of +/- 0.75 G, and a frequency equal to the paced-heart frequency (2--3 Hz). When the peak force was positive in early systole, and negative in early diastole, changes in myocardial oxygen consumption (MVo2, + 8%), mean coronary flow (MCF, + 8%), stroke volume (SV, + 15%), cardiac work (CW, + 19%) and the time derivative of left ventricular pressure (dP/dt, + 18%) were minimal in comparison to nonoscillatory control values. When the peak force was positive in early diastole and negative in late diastole and early systole, changes in MVo2 (+ 41%), MCF (+ 39%), SV (+ 33%), CW (+ 50%), and dP/dt (+ 31%) were maximal. Thus the capability of EASE to produce a range of desired sustained CV responses provides a basis for its potential diagnostic/therapeutic applications.


Pulmonary pressure-flow curves measured by a data-averaging circuit.

We measured pulmonary pressure-flow curves in nine normal nonsmoking subjects using a data-averaging circuit. With this method we obtained mean pressure flow curves of 20 consecutive breaths free of cardiac artifacts. Within-observer and within-subject-within-day reproducibility were good especially for the inspiratory limb of the curve. Within-subject-between-day variability in curvilinearity was substantial. In most subjects there was a continuous increase in resistance throughout the course of expiration even though the airways did not become dynamically compressed. This resulted in a mean value of expiratory resistance that was greater than during inspiration. Resistance early in expiration, however, was identical to that during inspiration. The data-averaging circuit allows for a more accurate assessment of the slope and the curvilinearity of pulmonary pressure-flow curves than other methods described before.


Measurement of transdiaphragmatic pressure with a single gastric-esophageal probe.

A single gastric-esophageal probe, 5 mm in diam, with two transducers mounted near the tip has been used to measure transdiaphragmatic pressure in human subjects. The transducers are linear up to at least 200 cmH2O pressure and provide equal deflections for both positive and negative pressures. The method is shown to give results comparable to the standard procedure using two balloon-tipped catheters, one in the stomach and one in the esophagus.


Effects of gas density on the frequency response of gas-filled pressure transducers.

The effects of gas density on the frequency responses of four pressure transducers were determined at gas densities from 1.2 to 25.0 g/l. Transducers tested included three sensitive differential types used with pneumotachographs to measure respiratory flow (Validyne DP-45 and DP-103; Medistor P-11) and a transducer commonly used to measure esophageal pressure (Statham P23Dd). Three different responses were obtained. The Validyne DP-103 was overdamped and its response was essentially independent of gas density. The frequency response of this transducer is adequate for use with quiet breathing only. The Validyne DP-45 and Medistor P-11 responses were underdamped. The resonant peaks of these transducers decreased markedly in frequency as the gas density increased. The Statham P23Dd was also underdamped; however, its resonant frequency increased as gas density increased. An esophageal balloon did not alter the frequency response characteristics of this tubing-transducer system. Both increases in length and decreases in diameter of connecting tubing reduced the frequency of resonant peaks of underdamped pressure transducers.


Electrocardiographic verification of esophageal temperature probe position.

Esophageal temperature (Tes) varies with depth of insertion. Characteristic features of the esophageal electrocardiogram (ECG) can be used to place probes in the region where the esophagus is between the aorta and the left atrium. This describes a suitable catheter for recording of Tes and ECG and how features of the electrical activity of the atria may be used to place the probe tip. Records of Tes versus depth obtained during heating of four human subjects are included. The technique eliminates the need for radiographic verification of probe position. It could readily be employed in clinical situations with the advantage of having both a central temperature and an electrocardiogram available from a simple, readily inserted, and readily tolerated catheter.


Effect of intracellular carbohydrates on heat resistance of Dictyostelium discoideum spores.

The effect of intracellular trehalose and glycogen on the survival of spores of Dictyostelium discoideum ATCC 25697 after exposure to supraoptimal temperatures was examined. Cells metabolically perturbed by incubation in glucose and inorganic phosphate have intracellular trehalose and glycogen concentrations fivefold and twofold higher, respectively, than those of the controls. These cells were more resistant to the lethal effects of wet heat (45 degrees to 55 degrees C) than were control cells. The presence of 40 mM trehalose in the buffer during heat stress increased the survival of nonperturbed cells to approximately the level of the perturbed cells. No protection was observed when cells were heated in the presence of exogenous glycogen. Glucose or disaccharides other than trehalose when present during heat stress, had no effect on heat resistance. Nonperturbed cells preincubated in 40 mM trehalose and washed before heat stress were more resistant to killing than were controls. Cells perturbed with inorganic phosphate, which has been shown to increase trehalose concentrations but decrease glycogen concentrations, were also more resistant to the lethal effects of wet heat than were controls. The data suggest that trehalose has an effect on the wet-heat resistance of D. discoideum. Some possible mechanisms are suggested.


Modulation of protein A formation in Staphylococcus aureus by genetic determinants for methicillin resistance.

Many methicillin-resistant (Mec(r)) strains of Staphylococcus aureus either produce no protein A or secrete it extracellularly (S. Winblad and C. Ericson, Acta Pathol. Microbiol. Scand. Sect. B 81:150-156, 1973). We found that methicillin resistance and protein A production were apparently lost coordinately from the natively Mec(r) strain A676. Restoration of the genetic determinant for methicillin resistance (mec) by transduction or transformation restored protein A production. In two other Mec(r) strains, loss of mec was accompanied by marked reduction in protein A formation. Genetic transfer of mec to derivatives of S. aureus 8325 affected protein A formation differently with different mec determinants. Those derived from strain A676 and two other Mec(r) strains reduced the scanty amount of protein A produced by strain 8325 to even lower or undetectable levels, whereas mec from two more Mec(r) strains increased its protein A content. This "mec-effect," i.e., stimulation or inhibition of protein A formation dependent on the combination of host strain and mec determinant, was reduced in methicillin-susceptible (Mec(s)) mutants produced by ethyl methane sulfonate treatment of Mec(r) strains. The mec-effect reappeared in spontaneous revertants to methicillin resistance. Phenotypic reduction of methicillin resistance in Mec(r) strains grown at 44 degrees C was accompanied by reduction of the mec-effect on protein A, but it had no effect on protein A formation in Mec(s) strains. Two independent mutants of strain 8325 produced large amounts of protein A at rates that were unaffected by growth at 44 degrees C or by the introduction of mec determinants.


Rapid screening procedure for detection of plasmids in streptococci.

An enrichment procedure, yielding plasmid deoxyribonucleic acid preparations normally containing less than 5% chromosomal contamination, has been devised for the isolation of plasmids from virtually all species of streptococci. The procedure is rapid, reproducible, and inexpensive, requiring no radioisotopes or density gradient centrifugation. The procedure can be used for routine screening of several hundred isolates in a short period of time, and plasmids obtained from 10- to 20-ml cultures can readily be visualized in agarose gels.


Local anesthetics block induction of the Pseudomonas alk regulon.

The local anesthetics procaine and piperocaine blocked induction of the plasmid-determined enzymatic activities involved in the metabolism of n-alkanes in Pseudomonas putida. Procaine reversibly inhibited existing alkane hydroxylase activity. Induction of a soluble aliphatic amidase activity was not affected. These results support the hypothesis that induction of the plasmid-determined alkane metabolic system in P. putida involves a membrane component(s).


Response of Pseudomonas cepacia to beta-Lactam antibiotics: utilization of penicillin G as the carbon source.

Pseudomonas cepacia utilized penicillin G as the sole source of carbon and energy. We report here an unexplained correlation between lysine auxotrophy and beta-lactamase deficiency, resulting in loss of capacity to utilize penicillin.


Chemosensory responses of Halobacterium halobium.

Responses of Halobacterium halobium cells to chemical stimuli have been shown by a capillary technique. Cells were attacted by D-glucose and several amino acids and repelled by phenol. Certain chemicals, such as acetate, benzoate, indole, and NiSO4, that are known to act as repellents of Escherichia coli cells served as attractants for Halobacterium. In the presence of ethionine, sensitivity to attractants was reduced. Arsenate prevented the attraction by glucose without lowering the cellular adenosine 5'-triphosphate level. The ability for chemo-accumulation toward glucose and histidine was interfered with by the formation of photosensory systems. Light-induced motor responses and chemosensory behavior toward glucose and histidine became detectable in the late stationary growth phase only. The behavior toward acetate and indole was not connected to photobehavior in that way: both substances acted as attractants already in the late log phase. Inhibition of bacteriorhodopsin synthesis by L-nicotine allowed chemo-accumulation toward glucose and histidine already in the late logarithmic phase.


Regulation of membrane peptides by the Pseudomonas plasmid alk regulon.

Pseudomonas putida strains carrying the plasmid alk genes will grow on n-alkanes. Induced alk+ strains contain membrane activities for alkane hydroxylation and dehydrogenation of aliphatic primary alcohols. P. putida cytoplasmic and outer membranes can be separated by sucrose gradient centrifugation after disruption of cells by either mild detergent lysis or passage through a French press. Both the membrane component of alkane hydroxylase and membrane alcohol dehydrogenase fractionated with the cytoplasmic membrane. Induction of the alk regulon resulted in the appearance of at least three new plasmid-determined cytoplasmic membrane peptides of about 59,000 (59K), 47,000 (47K), and 40,000 (40K) daltons as well as the disappearance of a pair of chromosomally encoded outer membrane peptides of about 43,000 daltons. The 40K peptide is the membrane component of alkane hydroxylase and the product of the plasmid alkB gene because the alkB1029 mutation altered the properties of alkane hydroxylase in whole cells, reduced its thermal stability in cell extracts, and led to increased electrophoretic mobility of the inducible 40K peptide. These results are consistent with a model for vectorial oxidation of n-alkanes in the cytoplasmic membrane of P. putida.


Presence and synthesis of cholesterol in stable staphylococcal L-forms.

The sterol which was present in two strains of a stable staphylococcal L-form was analyzed by gas-liquid chromatography and combined gas-liquid chromatography-mass spectrometry. The retention time of the sterol on gas-liquid chromatography was the same as that of authentic cholesterol. Analysis of the sterol by mass spectrometry showed a molecular ion at an m/e of 386 and the same patterns of major ions above an m/e of 145 as those of authentic cholesterol. As a result, the sterol in staphylococcal L-form was identified as cholesterol. A parent strain and its L-forms were cultured in medium containing [14C]acetate, and the synthesis of cholesterol was examined. In the L-forms, 0.52% of the total lipid radioactivity was found in cholesterol fraction, whereas no significant radioactivity was detected in the cholesterol fraction of the parent strain, indicating that staphylococcal L-forms have acquired the capacity to synthesize cholesterol.


Carotenoids acts as reinforcers of the Acholeplasma laidlawii lipid bilayer.

Acholeplasma laidlawii cells grown with oleic acid produced much more colored carotenoids than did cells grown with elaidic acid. The amount of carotenoids was decreased 80 to 90% by growing the cells with 0.05 M propionate, resulting in a marked increase in the mobility of both 5-doxylstearate and 12-doxylstearate incorporated into the membranes. The fatty acid composition of the propionate-grown cells differed from that of cells grown without propionate by containing odd-numbered rather than even-numbered saturated fatty acids, but the ratios of saturated to unsaturated fatty acids were the same. To determine whether the carotenoids are the cause for the restricted mobility in the membranes, the carotenoids were selectively removed from A. laidlawii membranes by incubating the membranes with phosphatidylcholine vesicles. The carotenoid-depleted membranes showed an increase in the mobility of the hydrocarbon chains of the spin-labeled fatty acids. Furthermore, the incorporation of carotenoids into artificial membrane vesicles restricted the mobility of the hydrocarbon chain. Our results support the notion that the carotenoids in A. laidlawii act as a rigid insert reinforcing the membrane bilayer.


In vitro binding of cloacin DF13 to its purified outer membrane receptor protein and effect of peptidoglycan on bacteriocin-receptor interaction.

The in vitro neutralization of the killing activity of cloacin DF13 by incubation with its purified receptor protein was shown to be the result of the formation of a direct and specific equimolar complex of both proteins. The binding of cloacin DF13 to its receptor protein did not result in a fragmentation of the cloacin molecules nor in the expulsion of immunity protein from the bacteriocin. The rate of the cloacin DF13-receptor interaction in vitro was found to be enhanced significantly in the presence of peptidoglycan, but lysozyme-treated peptidoglycan did not affect this interaction. Incubation of the cloacin DF13 as well as its receptor protein with peptidoglycan showed that the receptor protein but not the cloacin DF13 was able to bind to the peptidoglycan.


Synthesis of alpha-ketoglutarate by reductive carboxylation of succinate in Veillonella, Selenomonas, and Bacteriodes species.

Evidence for reductive carboxylation of succinate to synthesize alpha-ketoglutarate was sought in anaerobic heterotrophs from the rumen and from other anaerobic habitats. Cultures were grown in media containing unlabeled energy substrates plus [14C]succinate, and synthesis of cellular glutamate with a much higher specific activity than that of cellular asparate was taken as evidence for alpha-ketoglutarate synthase activity. Our results indicate alpha-ketoglutarate synthase functions in Selenomonas ruminantium, Veillonella alcalescens, Bacteroides fragilis, Bacteroides vulgatus, Bacteroides uniformis, Bacteroides distasonis, and Bacteroides multiacidus. Evidence for this carboxylation was not found in strains representative of 10 other species.


A gigantic basal-cell carcinoma on the plantar arch of a foot: report of a case.

A rare case of a large basal-cell carcinoma on the plantar arch of a sole and its ablation by Mohs' fresh-tissue technique are described.


Debrisan as a postoperative dressing after dermabrasion.

Beads of the material that is commercially purveyed as Debrisan were used as a postoperative dressing after dermabrasion in 24 patients. Fifteen of seventeen patients so dressed on only half of the dermabraded area expressed preference for it. The beads absorbed drainage and were protective of the dermabraded half. Five of the seventeen patients developed milia one month after dermabrasion and three of the five had them only on the side treated with the beads of Debrisan.


Techniques of biopsy of cutaneous neoplasms.

General principles of biopsy technique of cutaneous malignancies are given and specific techniques are described in detail for lesions of different types. Schematic drawings further elucidate subtleties not easily put into words.


Systematic bacteriological monitoring of intensive care unit patients: the results of a twelve month study.

The results from the bacteriological monitoring of 464 ITU patients are presented. The specimens analysed include urine, sputa, tracheostomy swabs, central venous pressure line catheter tips, blood cultures, wound drainage fluid, cerebro-spinal fluid, pleural fluid and peritoneal dialysate samples. Guidelines which may be used to differentiate between colonisation and infection and factors, notably those related to antibiotic usage, which are associated with increased risk of infection are described. Certain bacterial and fungal infections which are more peculiar to the compromised host are also discussed.


The effect of dopamine on hepatic-splanchnic blood flow after open heart surgery.

Dopamine (3,4 dihydroxyphenylethylamine) increases cardiac output and in particular the renal blood flow at the expense of other regional vascular beds not yet defined. Since the results of dopamine-induced changes in splanchnic perfusion are inconsistent, the effect of 6 mcg/kg/min dopamine was studied in 9 patients early after open heart surgery. Estimated hepatic blood flow (EHBF) was calculated from the concentration-time slopes of Indocyanine Green (ICG, Cardiogreen) in arterial and hepatic venous blood following single intravenous injection. Blood volume was measured using 51Cr tagged red cells. Cardiac output was determined according to the Fick method. 6 mcg/kg/min dopamine caused a mean EHBF-increase of 82%, from 492 +/- 64 to 824 +/- 80 ml/min/m2 (P less than 0.001). Related to the corresponding increase in cardiac index (CI) from 2.6 +/- 0.2 to 3.8 +/- 0.3 1/min/m2 (P less than 0.001), the EHBF/CI-ratio changed from 18.5 to 21.7% (P less than 0.025). The arterial-hepatic venous oxygen difference was reduced from 7.40 +/- 0.53 to 4.91 +/- 0.60 Vol% (P less than 0.001). It was concluded that splanchnic perfusion does not contribute to the preferential increase of renal blood flow under dopamine under the above mentioned conditions. Dopamine had the most beneficial effect on EHBF in two cases where the latter was severely reduced.


Complete cerebral recovery after prolonged circulatory arrest. A report of two cases.

Two adult patients with severe heart disease regained full consciousness a few hours after circulatory arrest at normal temperature which lasted up to eighteen minutes, though both eventually died. Whilst the reason for their unusual cerebral recovery cannot be clearly established, it may have been primarily due to the cause of the circulatory arrest, exsanguinating haemorrhage during cardiac surgery, together with subsequent circulatory support. Several other factors may also have contributed to this outcome, but a review of present evidence suggests they were of much less importance.


A newly designed flexible fiberoptic bronchoscope for use in intensive care units.

A newly designed flexible fibroptic bronchoscope has been manufactured for use in intensive care units (ICU). It has an inside channel of large caliber, diameter 2.5 mm, through which pulmonary secretions can be aspirated directly via the suction tube. Furthermore, prompt bedside use is possible since handle type batteries can easily be attached to the bronchofibroscope. This new instrument is now employed in our ICU for: 1. The diagnosis and treatment of atelectasis. 2. Suction of retained secretions. 3. Detection of tracheal obstruction. 4. Evaluation of endotracheal and tracheostomy tubes whilst in position. 5. Observation of tracheal and bronchial changes. 6. Help in endotracheal intubation. It was used most frequently for the diagnosis and treatment of atelectasis and suction of retained secretions.


Sterol synthesis: studies of the metabolism of 14 alpha-methyl-5 alpha-cholest-7-en-3 beta-ol.

[3 alpha-3H]14 alpha-Methyl-5 alpha-cholest-7-en-3 beta-ol has been prepared by chemical synthesis. The metabolism of this compound has been studied in the 10,000 g supernatant fraction of liver homogenates of female rats. Efficient conversion to cholesterol was observed. Other labeled compounds recovered after incubation of [3 alpha-3H]14 alpha-methyl-5 alpha-cholest-7-en-3 beta-ol with the enzyme preparations include the unreacted substrate, 5 alpha-cholesta-7,14-dien-3 beta-ol, 5 alpha-cholesta-8,14-dien-3 beta-ol, cholesta-5,7-dien-3 beta-ol, 5 alpha-cholest-8(14)-en-3 beta-ol, 5 alpha-cholest-8-en-3 beta-ol, and 5 alpha-cholest-7-en-3 beta-ol. In addition, significant amounts of incubated radioactivity were recovered in steryl esters. The steroidal components of these esters were found to contain labeled 14 alpha-methyl-5 alpha-cholest-7-en-3 beta-ol, 5 alpha-cholesta-8,14-dien-3 beta-ol, 5 alpha-cholesta-7,14-dien-3 beta-ol, 5 alpha-cholest-8-en-3 beta-ol, 5 alpha-cholest-7-en-3 beta-ol, and cholesterol.


Quantitative analysis of monosialogangliosides by high-performance liquid chromatography of their perbenzoyl derivatives.

A quantitative high-performance liquid chromatographic method for the analysis of monosialogangliosides as their perbenzoyl derivatives has been devised. Samples containing as little as 3 nmol were converted to their perbenzoyl derivatives by reaction with 0.1 ml of 10% benzoyl chloride in pyridine at 60 degrees C for 1 hr. The products were purified by silicic acid chromatography and analyzed by high-performance liquid chromatography (HPLC). The HPLC analysis was performed with a 50 cm X 2.1 mm LiChrosphere SI 4000 column and a linear gradient of 7-23% dioxane in hexane in 18 min. Detection was at 230 nm. The detector response was found to be proportional to the amount of monosialoganglioside analyzed. As little as 50 pmol of injected material could be conveniently quantitated. The overall yield from derivatization and chromatography, as determined with radiolabeled GM1, was found to be 86%. To take advantage of the high sensitivity of the HPLC, a small-scale isolation method for gangliosides was devised. This method coupled with HPLC isotope dilution analysis was used to analyze the GM3 content of 1 ml of human plasma.


A rapid radioassay procedure for plasma lecithin-cholesterol acyltransferase.

A rapid and accurate single step procedure is described for the assay of lecithin-cholesterol acyltransferase activity. After incubation, using radiolabeled cholesterol as the substrate, an ethanolic solution of digitonin is added directly to the incubation mixture to extract the lipids. Excess cholesterol is then added, and the labeled cholesterol-digitonide along with denatured proteins are sedimented by low speed centrifugation, leaving the labeled esterified cholesterol in solution. An aliquot of the supernatant is counted in an aqueous scintillation mixture. The method correlates well with the established thin-layer chromatographic procedure using either lecithin-cholesterol vesicles or heat-inactivated plasma as the substrate for lecithin-cholesterol acyltransferase.


These studies were designed to determine the importance of the rate of hepatic cholesterol synthesis, the size of the hepatic cholesteryl ester pool, the amount of chylomicron cholesterol reaching the liver, and the rate of bile acid transport into bile as determinants of the rate of biliary cholesterol output. Female rats that had been subjected to diurnal light cycling, fasting for 48 hr, intravenous administration of chylomicrons, and diets containing either cholestyramine, cholesterol, or bile acid underwent total biliary diversion for 2 hr. The animals were then killed and the rates of hepatic cholesterol synthesis and levels of hepatic esterified cholesterol were measured along with biliary lipid concentrations. Despite a 1000-fold variation in the rate of hepatic cholesterogenesis and a 100-fold variation in the levels of cholesteryl esters, the output and molar percentage of cholesterol in bile remained essentially constant with the exception of an approximate doubling in the output of cholesterol, as well as of bile acid and phospholipid in those animals fed bile acid. However, in this latter group the molar percentage of each component was unchanged. The administration of a bolus of chylomicrons did not alter output or molar percentage of cholesterol. Total biliary diversion for 36 hr and bile acid infusion were used to markedly vary the rate of biliary bile acid output. Cholesterol and phospholipid output remained tightly coupled to bile acid output over almost a 40-fold range. In other experiments it was shown that biliary cholesterol output could be driven by bile acid infusion to a similar extent in rats in which the rate of hepatic cholesterogenesis had been varied over a 26-fold range. It was concluded that the rate of hepatic cholesterol synthesis, the level of hepatic cholesteryl esters, and the amount of cholesterol absorbed from the diet play no role in determining the rate of biliary cholesterol secretion, at least in this species.-Turley, S. D., and J. M. Dietschy. Regulation of biliary cholesterol output in the rat: dissociation from the rate of hepatic cholesterol synthesis, the size of the hepatic cholesteryl ester pool, and the hepatic uptake of chylomicron cholesterol.


Configuration at C-25 in 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestan-26-oic acid by X-ray crystallography.

The two diastereoisomers at carbon-25 of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestan-26-oic acid, a key intermediate in the biosynthetic pathway of cholic acid, were obtained in pure form by a combination of fractional crystallization and thin-layer chromatography. The configuration at C-25 of these two isomers was established by X-ray crystallography as 25S for one diastereoisomer (mp 199-201 degrees C) and 25R for the other (mp 180-182 degrees C). These findings permit us to determine, unequivocally, the configuration of this naturally occurring C27-bile acid in man and other animals and to establish the stereospecificity of the microsomal and mitochondrial omega-hydroxylation pathway for the side-chain oxidation of cholesterol to bile acids.


Origin of cholesterol transported in intestinal lymph: studies in patients with filarial chyluria.

In subjects fed a cholesterol-free diet there are three possible sources of intestinal lymph cholesterol: a) mucosal synthesis; b) absorption of endogenous (biliary) cholesterol; and c) transudation of plasma lipoproteins into the lacteals of the intestinal wall. To test these possibilities, the extent of transudation was measured by means of [3H]beta-sitosterol administered intravenously as a marker. Absorption of biliary cholesterol was reduced by oral administration of beta-sitosterol (9 g/day), and mucosal synthesis of cholesterol was evaluated by comparisons of plasma/lymph [14C]cholesterol specific activity ratios after intravenous administration of a single dose of labeled cholesterol. Studies were carried out on six patients with filarial chyluria. In five patients fed a cholesterol-free diet the results indicated that lymph cholesterol was largely derived by transudation of plasma lipoproteins into the lacteals from the intestinal blood supply, without contribution from de novo mucosal synthesis or from absorption of endogenous cholesterol. The intestinal lymph of one patient fed cholesterol (2 g/day) contained cholesterol originating mostly from plasma transudation and from dietary absorption, with little contribution from absorbed endogenous cholesterol. In all experiments the larger part of the cholesterol transported away from the intestine in the lymph was carried in chylomicrons, even though it had its origin in plasma lipoproteins.


Enzymatic sulfation of glycochenodeoxycholic acid by tissue fractions from adult hamsters.

Using a radiometric assay with glycochenodeoxycholic acid as substrate, bile acid:3'-phosphoadenosine-5'-phosphosulfate sulfotransferase activity was found in 105,000 g supernatant fractions of liver, proximal intestine, and adrenal gland homogenates from adult hamsters. Optimum conditions for measurement of the hepatic enzyme were determined. In both male and female animals sulfation only occurred at the 7 alpha-position. Saturation analysis with glycohenodeoxycholic acid revealed that the higher activity observed in fractions from female compared to male hamsters was due to a 4-fold lower apparent Km (79 muM vs. 317 muM) for this bile acid in the females. The sulfation of glycohenodeoxycholic acid was competitively inhibited by glycolithocholic acid, chenodeoxycholic acid, and ursodeoxycholic acid. The data are consistent with the concept that sulfation of many, if not all, bile acids can occur in vivo.


To further elucidate the role of bis(monoacylglycero)phosphate in lysosomes, its metabolism was assessed by incubation of intact and disrupted macrophages in the presence of labeled lipid precursors. In rabbit pulmonary macrophages bis(monoacylglycero)P accounted for 17.9% and acylphosphatidylglycerol for 2.6% of phospholipid phosphorus. Major fatty acids in bis(monoacylglycero)P were oleic (47%), linoleic (29%), and arachidonic (6.4%); those in acylphosphatidylglycerol were of similar distribution except for a high content of palmitic acid (20%). When homogenates of rabbit pulmonary and peritoneal macrophages, rat pulmonary macrophages, and human blood leukocytes were incubated with sn[(14)C]glycerol-3-phosphate and CDP-diacylglycerol at pH 7.4, there was labeling of bis(monoacylglycero)P and acylphosphatidylglycerol that correlated with content of bis(monoacylglycero)P. When intact rabbit pulmonary macrophages were incubated for 60 min with [(3)H]glucose and [(32)P]orthophosphate, small amounts of label appeared in bis(monoacylglycero)P and only traces in acylphosphatidylglycerol. In contrast, incubation of intact cells with the (14)C-labeled fatty acid precursors palmitic, oleic, and arachidonic acids resulted in much greater labeling of the two lipids. Labeling of phospholipids was greatest with arachidonate as precursor and least with palmitate; after 60 min, labeling of bis(monoacylglycero)P with arachidonate was 10- and 50-fold greater than with oleate and palmitate, respectively, and was exceeded only by that of phosphatidylcholine. Calculated ratios of labeling of fatty acid to P, particularly those for arachidonate, were much greater for bis(monoacylglycero)P and for acylphosphatidylglycerol than for other phospholipids. This suggests a uniquely high turnover of fatty acids in bis(monoacylglycero)P and acylphosphatidylglycerol and thus a more specific role for these compounds in metabolism of complex lipids in the lysosome.-Huterer, S., and J. Wherrett. Metabolism of bis(monoacylglycero)phosphate in macrophages.


Inhibition of sterol biosynthesis in animal cells by 14 alpha-alkyl-substituted 15-oxygenated sterols.

Reported herein are the results of investigations of the effects of a number of 14 alpha-alkyl-substituted 15-oxygenated sterols, prepared by chemical synthesis, on sterol biosynthesis and the levels of 3-hydroxy-3-methylglutaryl CoA reductase activity in L cells and in primary cultures of fetal mouse liver cells grown in serum-free media. Several of the compounds, most notably 14 alpha-ethyl-5 alpha-cholest-7-en-3 beta, 15 alpha-diol and 14 alpha-ethyl-5 alpha-cholest-7-en-15 alpha-ol-3-one, were found to be extraordinarily potent inhibitors of sterol synthesis in these cells. For example, the latter compound caused a 50% inhibition of the incorporation of labeled acetate into digitonin-precipitable sterols in L cells in culture at a concentration of 6 X 10(-9) M.


Effect of word meaningfulness on primary and secondary memory.

An experiment was carried out to determine the effects of mode of presentation (auditory or visual) and work meaningfulness on primary and secondary components of free recall (N = 80 female undergraduates). The results indicated that (a) word meaningfulness affected both primary and secondary memory, (b) visual presentation was superior to auditory presentation in secondary memory but auditory presentation was superior to visual presentation in primary memory (the modality effect), and (c) the modality effect was independent of word meaningfulness. It is suggested that there are modality-specific stores in primary memory, and that these stores can employ different forms of coding.


The influence of the labeling of pictures of "borderline meaningfulness" on recall and recognition.

An attempt was made to enhance (by means of instruction) the verbal labeling and recall of schematic pictures which uninformed Ss tended to perceive as senseless. Sixty-nine male and female  undergraduate students in psychology, about 19 years of age, took part in the experiment. Ss were confronted with 16 schematic pictures half of which referred to a predefined semantical category. In Condition I Ss were informed in advance that some of the pictures belonged to the predefined category. In Condition II the pictures were presented as senseless. In Condition III information about the belonging of some of the items to one semantical category was postponed until just prior to free recall. The results indicated that verbal labeling of the pictures involved was stimulated by appropriate instruction, enhancing later free recall. However, the critical information had to be given prior to actual learning. In a subsequent test for recognition no differences were observed between the conditions.


An auditory von Restorff effect.

In this experiment 60 undergraduates were given a serial learning task to assess the possibility of an auditory von Restorff effect. Fifteen males and 15 females learned a list of nine words presented aurally (recorded) with the same male voice (control groups). Fifteen males and 15 females (experimental groups) learned the same list as the control groups except that the sixth word was spoken by a female voice: i.e., it was isolated. The results of this study parallel the results of studies using visual stimuli. The von Restorff effect was demonstrated with auditory stimuli in that one of the experimental groups (female) learned the list with significantly fewer errors than the comparable control group. No difference was found between the male groups.


Verbal vs. nonverbal and complex vs. simple responses in the paired-associate learning of poor readers.

The relative ability of 38 fourth-grade boys, good and poor readers, to learn paired-associate lists requiring either verbal or nonverbal responses was assessed with four different tasks. Two of the tasks required either simple or complex verbal responses, while the other two involved learning simple and complex oral, nonverbal responses. The stimuli for all tasks were letter-like visual figures drawn on cards. The good readers learned more efficiently overall, but the major differences between reading groups occurred on the tasks requiring verbal responses.


The role of sensory attributes as retrieval cues or as interference in retrieval of information from episodic memory.

The sensoty attributes of to-be-remembered (TBR) events and of distractor stimuli were systematically manipulated (both within and between modalities) in two Brown-Peterson tasks [experiments 1 (N = 40 male and female university students or faculty) and 2 (N - 22 male and female undergraduates)] and in a delayed recognition task (Experiment 1). Performance on these recall and recognition tasks (in which the semantic attributes of the TBR events were relatively controlled) was consistent with episodic theory. Memory of an event was reasonably completely described in terms of (a) the degree of overlap between the perceptible properties of the retrieval environment and of the memory trace of the event and (b) the perceptible similarities between the memory trace of the event and the traces of information encoded temporally adjacent to it. These sensory encoding specificity effects (as well as other research reviewed) were interpreted as demonstrations that a semantic interpretation of the encoding specificity principle cannot account for all encoding specificity phenomena.


Signal detection analysis of conditioning data.

Signal detection analysis of learning and conditioning data provides for a greater distinction to be made between learning and performance through the use of the two signal detection parameters, d' and B. The use of the two parameters permits alternative interpretation of several types of data sets discussed. This analytic technique may be used with either discrete trial or free-response data. The present article reveiws applications of signal detection parameters in the literature, and provides for their extension to other uses.


Measurements of excitatory postsynaptic potentials in the stretch reflex of normal subjects and spastic patients.

The patellar tendon was tapped by random impulses of triangular waveform and motor unit spikes were recorded from the quadriceps femoris muscle. The cross-correlogram of the taps and the motor unit spikes revealed a primary correlation kernel, the width of which was interpreted as an indicator of the mean time-to-peak of excitatory postsynaptic potentials (EPSPs) elicited monosynaptically in an alpha-motoneurone by the triangular taps. The mean time-to-peak was 7.6 +/- 1.3 ms in normal subjects and 9.0 +/- 1.8 ms in spastic patients (P less than 0.005). The prolonged time-to-peak of EPSP in spastic patients is consistent with the hypothesis that as a result of degeneration of the corticomotoneuronal tract the Ia axons sprout and form more synaptic contacts on distal portions of the dendrites of alpha-motoneurones.


Phonological alexia: three dissociations.

Three dissociations were observed in a case of alexia: a disturbance of reading, without comparable disturbance of oral expression, oral comprehension, writing, or spelling aloud; a disturbance of the phonological reading process, without disturbance of the non-phonological reading process; a disturbance located at the level of the phonological stage, without disturbance of the perceptual and expressive stages. This pattern of results has been called phonological alexia.


Phonological processing in reading: data from alexia.

The reading of four subjects suffering from a phonological reading impairment as a result of a cerebral lesion was tested. A double dissociation observed in their results is strong evidence for the existence of two functionally independent kinds of phonological processing in reading--a graphemic and a phonetic one.


Semiquantitative evaluation of ophthalmic collateral flow in carotid artery occlusion: ultrasonic doppler study.

The reliability of quantitative evaluation by doppler ultrasound with regard to the ophthalmic collateral blood flow in patients with carotid artery occlusion was estimated. The ultrasonic doppler flow signals of the ophthalmic collateral flow of 54 carotid occlusions were classified into four types and three degrees--high, moderate, and low reversed flow patterns--and were compared with the angiographic findings of the collateral flow classified into three grades--good, poor, and none. With the exception of three cases, the ultrasonic doppler flow patterns of the collateral flow correlated well with the angiographic findings in 54 occluded carotid arteries.


Effects of long-term antihypertensive treatment on brain metabolism after bilateral carotid artery occlusion in spontaneously hypertensive rats.

The effects of antihypertensive treatment on brain metabolism after bilateral carotid occlusion were studied in spontaneously hypertensive rats. The results indicate that an increase in metabolites of ischaemic brain such as lactate and the lactate/pyruvate ratio after carotid occlusion in spontaneously hypertensive rats is apparently suppressed by treating hypertension. This suggests that hypertension may play an important role in susceptibility to cerebral ischaemia.


Single fibre electromyographic jitter in multiple sclerosis.

Recent histological and electrophysiological reports have given evidence for peripheral nervous system (PNS) involvement in multiple sclerosis. We have applied the single fibre electromyography (SFEMG) technique to 15 patients with multiple sclerosis. Six patients had clearly abnormal jitter and two of these had previously undiagnosed coexistent peripheral neuropathy. A further five patients had borderline abnormalities of SFEMG. The mean jitter for each patient was abnormal in 10 patients. This was clear evidence for PNS involvement in this disease. Theoretically, the site of the abnormality could be in the terminal nerve network or at the neuromuscular junction, but this technique cannot distinguish between these sites.