Serology of amebiasis using the FIAX-TM system.

A new fluorescent immunoassay system (FIAX TM) has permitted development of a promising serologic test for amebiasis. The test is similar but far superior to the soluble antigen fluorescent antibody test. The main differences are the unique StiQ TM sampler and the flourometer itself. Quantitative results can be obtained from a single standard dilution of serum. The procedure is simple to perform, gives objective readings, and uses the proven principle of immunofluorescence. It is possible to test for different immunoglobulin classes and to use purified antigen prepared from axenically  cultured Entamoeba histolytica. Conservation of reagents is comparable to microplate systems, and results are available in less than two hours. FIAX TM for amebiasis has demonstrated excellent discriminating power between amebic and nonamebic sera. Sensitivity is 100 percent for extra-intestinal amebiasis (33 sera), 90 percent for symptomatic intestinal amebiasis (20 sera), and 43 percent for asymptomatic amebiasis (seven sera). Specificity is 97 percent (158 sera).


[Intestinal amebiasis in children. I. Etiological study of colonic lesions of the rectosigmoid colon].

A total of 253 children from two months to 12 years old, who had diarrheic or dysenteric syndromes, were studied from the rectosigmoidoscopic and parasitologic points of view. In addition, 112 and 20 of these patients were also studied bacteriologically and virologically, respectively. Only in 28 patients torphozoites of Entamoeba histolytica were found by means of direct microscopic examination, staining techniques and amoebal cultures. Enteropathogenic bacteria were isolated in 41 of the 112 cases examined. No viral particles were detected in the 20 cases studied. From the discussion of these results, the conclusion is reached that the rectosigmoidal mucusal alterations which have been currently considered as suggesting amoebal lessions are not characteristic of invasive intestinal amebiasis in children.


[Effect of alpha, beta blocker, labetol on the angiotensin renin system in arterial hypertension].

The effect of labetalol, a new alpha and beta adrenergic blocker, on blood pressure, heart rate, plasma renin activity (PRA), and urinary aldosterone excretion was assessed in 23 essential hypertensive patients, divided in 2 subgroups: 11 with normal electrocardiogram and 12 with left ventricular hypertrophy (LVH). In the first subgroup significant differences were found in the arithmethyc mean for sistolic blood pressure in sitting position (control: 166.1 +/- 17.2 mm of Hg treatment: 153.9 +/- 13.8, p less than or equal to 0.005) and in standing position (control: 165.3 +/- 17.3, treatment: 152.8 +/- 13.8, p less than or equal to 0.005) and for diastolic blood pressure (control: 102.7 +/- 12.6 to 89.9 +/- 10.1, p less than or equal to 0.001 and 103.2 +/- 11.8 to 91.2 +/- 10.8, p less than or equal to 0.001; in sitting and orthostatic positions, respectively.). No significant differences were found in the group with LVH. Heart rate decreased in the total population during treatment (- 6.0 +/- 7.5, p less than or equal to 0.05 and - 5.4 +/- 7.5 beats per minute, p less than or equal to 0.05 in sitting and orthostatic positions, respectively. PRA diminished in 12 of 15 cases studied (- 2.5 +/- 4.65 ng/ml/hr., p greater than 0.5). Correlation coefficient between decrements of diastolic blood pressure (sitting position) and ARP was 0.637. Aldosterone decreased in a non significant way during treatment. These data support the thesis of an important role of the adrenergic system in the pathogenesis of non complicated essential hypertension and, therefore, simultaneous alpha and beta receptor blockade in these cases has a better therapeutic effect. The good correlation between the decrements of ARP and blood pressure suggests an intervention of the inhibition of renin angiotensine system, brought about by the blocker property of labetalol, in the antihypertensive mechanism of the drug.


[Arterial hypertension. Considerations on its current status in Mexico. In memory of Samuel Zajarias].

The present article summarises statistical information about the problem of hypertension in this country making reference to international and national epidemiological works, with the purpose of evaluating the problem in community. Includes information about the clino-pathologic experience acheived at the National Institute of Cardiology of Mexico. The data is analyzed and commented from the point of view of how worth might be to study hypertension in Mexico.


Plasma-membrane lipid composition and ethanol tolerance in Saccharomyces cerevisiae.

Populations of cells suspended anaerobically in buffered (pH 4.5) M ethanol remained viable to a greater extent when their plasma membranes were enriched in linoleyl rather than oleyl residues irrespective of the nature of the sterol enrichment. However, populations with membranes enriched in ergosterol or stigmasterol and linoleyl residues were more resistant to ethanol than populations enriched in campesterol or cholesterol and linoleyl residues. Populations enriched in ergosterol and cetoleic acid lost viability at about the same rate as those enriched in oleyl residues, while populations grown in the presence of this sterol and palmitoleic acid were more resistant to ethanol. Suspending cells in buffered ethanol for up to 24 h did not lower the ethanol concentration.


Pole cap formation in Escherichia coli following induction of the maltose-binding protein.

After induction with maltose, 30--40% of the total protein in the osmotic shock fluid consist of maltose-binding protein while the induction ratio (maltose versus glycerol grown cells) for the amount of binding protein synthesized as well as for maltose transport is in the order of 10. Induction of maltose transport does not occur during all times of the cell cycle, but only shortly before cell division. Electronmicroscopic analysis of cells grown logarithmically on glycerol or maltose revealed in the latter the formation of large pole caps. These pole caps arise from an enlargement of the periplasmic space. Small cells contain one pole cap, large cells contain two. Pulse label studies with strain BUG-6, a mutant that is temperature sensitive for cell division reveal the following: Growth at the non-permissive temperature prevents maltose-binding protein synthesis and formation of new transport capacity. After shifting to the permissive temperature the cells regain both functions. Simultaneously, the newly formed cells exhibit pole caps. We conclude that the induction of maltose-binding protein is responsible for the formation of pole caps. In addition, beside the presence of inducer, cell cycle events occuring during division are necessary for the synthesis of maltose-binding protein.


Protoplast-like structures formation from two species of Enterobacteriaceae by fosfomycin treatment.

A procedure for protoplasts formation from Escherichia coli and Serratia marcescens by treatment with fosfomycin alone is described. This method gives high and low yields of stable protoplasts from E. coli and S. marcescens respectively. In the last case numerous spheroplasts were obtained. Electron micrographs of intact cells, protoplasts and spheroplasts are shown.


[Test of 0,0-dimethyl (l-hydroxy-2,2,2-trichloroethyl)-phosphonate (trichlorfon) for carcinogenic activity in mice by oral (oesophageal-gastric intubation), intraperitoneal and dermal application (author's transl)].

0,0-Dimethyl(1-hydroxy-2,2,2-trichloroethyl)-phosphonate (Trichlorfon; TCP) was tested for carcinogenic activity in male and female mice derived from strain AB/Jena by oral (oesophageal-gastric intubation), intraperitoneal and dermal administration. The maximum period of treatment was 73 (oral), 73 (intraperitoneal) or 75 (dermal) weeks. During this period the following maximum mean total doses of TCP per animal had been administered: 157.5 mg(male, oral), 154 mg (female, oral), 160.8 mg (male, intraperitoneal), 149.7 mg (female, intraperitoneal). The dermally treated male and female mice had received a maximum total dose of 375 mg per animal. The study was terminated at 80 weeks. There is no statistic significant difference when compared the total tumour incidence of TCP-treated animals and control mice or the incidence of the different corresponding groups of mice separated by the route of administration or the incidence of malignant and benign tumours separated for the different groups. These findings were independent from whether the groups of TCP-treated animals and solvent control animals were combined or divided by sex for comparison.


Clinical and toxicological investigations of a case of delayed neuropathy in man after acute poisoning by an organophosphorus pesticide.

Progressive neuropathy developed in a man during 2--8 weeks after acute poisoning by a pesticide said to contain trichlorphon. The neuropathy was typical of that caused by organophosphorus esters in the delay and in the maintenance of normal conduction velocity in surviving nerve fibres. A sample alleged to be typical of the ingested material was not more active against hen brain neurotoxic esterase (NTE) than was pure trichlorphon. Delayed neuropathy has never been produced in hens by a single dose of trichlorphon. This incident and studies of human brain in vitro suggest that the ratio neurotoxicity/lethality for trichlorphon is higher in man than in the hen. Suggestion is made of laboratory tests to improve neurotoxicity screening.


[Electron-microscopic and autoradiographic study of giant cells of foreign bodies in the focus of aseptic inflammation].

Ultrastructure of sinuous proximal and straight distal tubules, as well as collecting tubules of the cortical layer in the rat kidney fixed with perfusion has been studied with electron microscopic morphometry 7--8 weeks after contralateral nephrectomy. The volume of mitochondria, the area of their crists, the area of the membranes in intracellular labyrinth and other morphometrical parameters have been calculated. Relative volume of mitochondria in the nephron areas studied does not change, while in the collecting tubules it is elevated. The area of crists in mitochondria and "coefficient of morphological organization level" of these organells in the proximal tubules are increased, in the distal do not change, in the collecting tubules increase again. Subcellular changes described are discussed mainly in terms of enhancement of concentrating function of the compensatory-hypertrophic kidney.


[Methods of histological treatment of the labyrinth].

The otic labyrinth presents one of the most difficult objects for histological investigations as it is situated in the thick layer of the temporal bone and has a very complex structure. At the same time, a method for treating this object is not given in general hand-books on pathological techniques. The methods for histological treatment of the otic labyrinth elaborated by Wittmaack and later on modified are presented in the article. Methods for fixation, vital fixation including, decalcination, dehydratation and saturation of the objects prepared for histological investigation are described in details. Methods for the temporal bone orientation in order to obtain sections of the internal otic structures in the most advantageous plane depending on the purpose and aim of the investigation are recommended.


Evaluation of through-and-through corneal sutures.

Sutures placed at the level of Descemet's membrane were compared with sutures placed through and through the full corneal thickness in 42 rabbit corneas using cataract and corneal wounds. The rabbits were killed, and sutures were removed at various postoperative periods up to four weeks. Evaluation of the wounds demonstrated that although the through-and-through technique provided good wound closure in the immediate postoperative period, the technique produced more damage to Descemet's membrane and to the endothelial cells, both at the time of suturing and at the time of suture removal, and tended to produce greater retrocorneal membrane formation. In addition, the through-and-through suturing technique was technically more difficult. In this study performed in rabbits, the one advantage of the through-and-through suture, ie, immediate posterior wound closure, was outweighed by its many disadvantages.


Virus replication in the digestive tract of ducks exposed by aerosol to type-A influenza.

Enteric infection and cloacal shedding of influenza virus was demonstrated in ducks exposed experimentally to an aerosol of an avirulent type-A influenza virus. The fluorescent-antibldy technique was used to identify sites of virus replication in the epithelial cells of the digestive tract and the bursa.


Resistance to the aminoglycoside antibiotic neamine in Escherichia coli. A new mutant whose NeaR phenotype results from the cumulative effects of two distinct mutations.

A spontaneous mutant of Escherichia coli (strain AB2847), selected for resistance to the aminoglycoside antibiotic neamine, shows severe restriction of amber suppressors in vivo. Ribosomes isolated from the mutant exhibit only low misreading in vitro in the presence of the antibiotic. Genetic and biochemical analyses indicate that the neamine-resistant phenotype is the result of two distinct mutations. The first, res3128, appears to affect the gene (strA) coding for the ribosomal protein S12. Although it leads to a restrictive phenotype it does not, however, confer resistance to streptomycin. The second mutation, X3128, is located between the sirA and AROB loci and is lethal when segregated from the res3128 mutation. It may affect the ribosome at the level of a post-translational modification.


[Manual lymph drainage].

The manual lymphdrainage is a special method of massage which is often used for cosmetical purposes. Methodology, mode of action and indications are presented and the results of treatment are reviewed.


[Acute febrile neutrophilic dermatosis--Sweet syndrome].

Since 1964 there are 65 women and 13 men with the typical features of Sweet syndrome reported. An additional case in a 40 year old man is the purpose of this review of the literature. The Sweet syndrome is mainly observed in the fourth and fifth decade of life and begins with typical symptoms of high temperatures, peripheral leucocytosis, with eminent red plaques showing bumpy surface. The histologic picture is not specific but characteristic. The onset of cutaneous eruption is preceded about 10 days by symptoms of influenza and infections of the upper respiratory tract. Sites of predilection are the surface of extremities, face, nape and superior trunk. Erythema nodosum like foci and acneiform lesions have been described. Histologically, there is a distinctive edema in the upper corium and perivascular infiltrates, consisting of polynuclear leucocytes with leucocytoclasia. The pathological process is interpreted as an immune complex disease, different from erythema exsudativum multiforme. There is reason to believe in an infectious allergic origin. During the acute state lesions may occur, provoked by unspecific trauma.


Identification and characterization of two new soluble nuclear antigens reactive with sera of patients with connective tissue diseases.

Two antigens, temporarily referred to as MU and TM antigens after the original serum, that are closely related to the nucleolus have been identified in the nuclear soluble extract. Both antigens reacted with the sera of a small number of patients with various connective tissue diseases, and both were different from antigens described previously in these disorders. MU antigen was sensitive to the digestion with RNase and trypsin, and was shown to be equivalent to the nuclear ribosomal components in the nuclear extract. TM antigen was resistant to the digestion with RNase and trypsin, and was localized in the nucleolus and extranucleolar portion of nuclei, but the precise nature of TM has not been established.


Relative reactivities of rheumatoid factors in serum and cells. Evidence for a selective deficiency in serum rheumatoid factor.

Investigations of rheumatoid factors by a hemolytic plaque forming cell assay of blood lymphocytes with sensitized sheep cells have suggested that the rheumatoid factors released from the cells have higher affinities for human IgG than do the rheumatoid factors measured in the patient's serum. This study reaffirms this observation and provides evidence that the reported differences are not artifacts of technique. The findings imply that rheumatoid factors of higher affinity for IgG than those of the serum are being released into the tissue fluids by lymphocytes and locally precipitated. Such rheumatoid factors may never reach the peripheral blood serum in detectable quantity or may do so only infrequently.


Methods for the assessment of the effects of drugs on coronary blood flow in man.

The methods currently available for measurement of coronary blood flow in man are reviewed and their advantages and limitations discussed. Most of the techniques are invasive and involve cardiac catheterization. The least invasive isotope techniques are either not quantitative or involve expensive equipment not available in many centres. Two of the most suitable methods for assessing the effects of drugs on coronary flow are coronary sinus thermodilution and isotope washout curves using 133xenon or [125I]-iodo-antipyrine. The ideal technique for measuring coronary blood flow has yet to be developed.


Plasma bromocriptine levels, clinical and growth hormone responses in Parkinsonism.

1. Plasma bromocriptine levels following separate oral doses of bromocriptine 12.5, 25, 50 and 100 mg have been determined in ten subjects with parkinsonism. 2. There was considerable variation between peak plasma bromocriptine levels in individual subjects after similar doses of bromocriptine. Peak levels occurred 30--210 min after dosage (mean 102 min). Peak clinical response, peak rise in plasma growth hormone level and fall in blood pressure followed shortly after peak bromocriptine levels occurred. 3. The shape of the plasma-time curve for bromocriptine was similar with all dosages. 4. There was no significant relationship between peak plasma bromocriptine levels, peak clinical response, peak increase in growth hormone and peak fall in blood pressure. However, the degree of improvement in the signs of parkinsonism was related to plasma bromocriptine levels was achieved. 5. Metoclopramide 60 mg pretreatment had no consistent effect upon plasma bromocriptine levels, the clinical or hormonal response.


Acebutolol in hypertension--double-blind trial against placebo.

1. Eleven hypertensive patients were studied in a double-blind comparison of acebutolol, a beta-adrenoceptor blocker, and placebo. 2. Optimum dosage defined in an open assessment varied from 200--600 mg twice daily. 3. Blood pressure and pulse rate fell significantly while patients were lying, standing and after exercise. 4. Blood pressure remained as well controlled on each patient's optimum daily dose when taken once daily, and assessed 24 h post dose. 5. There was no correlation between blood pressure reduction and changes in heart rate. On once daily therapy while blood pressure remained unchanged at 24 h post dose there was a signficant reduction in beta-adrenoceptor blockade as measured by percentage reduction in exercise tachycardia. 6. There was no significant change in urinary catecholamine excretion or echocardiographically estimated cardiac output. 7. A correlation was found between the change in plasma renin activity (log transformed) and blood pressure reduction.


A double-blind comparison of the effects of hydrochlorothiazide and tienylic acid (a diuretic with uricosuric properties) in hypertension.

1. A double-blind comparison of the effect of tienylic acid and hydrochlorothiazide on blood pressure was made in patients with moderate hypertension. 2. The antihypertensive effect of 500 mg tienylic acid was comparable to 100 mg hydrochlorothiazide; mean decrease in supine blood pressure after 6 weeks treatment was 20/12 mmHg with tienylic acid and 17/9 mmHg with hydrochlorothiazide. Onset of antihypertensive action was within 1 week and was associated with significant weight loss. 3. Tienylic acid caused a marked decrease in serum uric acid to a mean of 0.18 mmol/1 (n = 11, P less than 0.001), this persisted through the treatment period and returned to placebo values 1 week after treatment ceased. Some patients had uric acid crystaluria and some had post-treatment uric acid levels higher than on placebo. 4. Tineylic acid and hydrochlorothiazide caused mild hypokalemia and alkalosis with proportional decrease in plasma chloride. 5. Blood urea and serum creatinine rose with both drugs and there was an unimportant decline in plasma sodium. 6. Tienylic acid is an effective antihypertensive agent with powerful uricosuric action and appears relatively free of side effects. Further studies are necessary to determine optimal dosage regimes and long term safety.


Rat lymphocyte mitogenesis by aggregation factor from rat ascites hepatoma cell surface.

Two-tumour-cell-aggregation factors derived from rat ascites hepatoma cells had different antigenicity; one, with a strong potency, was not absorbed by immunoadsorbent chromatography with anti-rat serum antibody and the other, with a weak potency, was. The unabsorbed factor possessed mitogenic activity on lymphocytes from thymus, spleen and lymph node of rats; its effect was compared with that of lectins (including phytohaemagglutinin, concanavalin A, pokeweed mitogen, lipopolysaccharide and soybean agglutinin) in the form of increased DNA and protein synthesis, blast transformation and mitosis. In the use of anti-thymocyte serum-resistant spleen cells and hydrocortisone-resistant thymocytes, the cells stimulated were assumed to be T-lymphocytes. DNA synthesis by this factor seemed to be characterized by a 2-step increase, suggesting the presence of 2 subpopulations of the cells activated, especially thymocytes. At high concentration this factor induced no depression of DNA synthesis. Favourable cell density for the response to this factor was 2-8 X 10(6) cells. Its effect was not influenced by treatment of the cells with neuraminidase.


A comparison of salbutamol given by pressure-packed aerosol or nebulization via IPPB in acute asthma.

Salbutamol was given by pressure-packed aerosol or nebulizer via IPPB to patients with acute asthma to compare the effectiveness of these methods of inhalation. The results show that both methods produce significant bronchodilatation even in patients admitted with moderately severe asthma (FEV1 about 38% predicted) but a slightly greater improvement may be achieved by IPPB nebulization. Our findings indicate that supervised inhalation of a pressure-packed aerosol of salbutamol may be useful for the initial treatment of asthmatic attacks but confirm the marginal advantage of IPPB nebulization, which should be reserved for patients unable to inhale from a pressure-packed aerosol or failing to respond to its treatment.


Sulfametopyrazine prophylaxis in chronic bronchitis.

From a double-blind randomized controlled trial by 32 general practitioners on 218 patients with chronic bronchitis it appeared that sulfametopyrazine given once a week over one winter reduced the number of respiratory illnesses and the loss of time from work to about half that of a control group. It had no effect on time off work in individual spells of illness nor on the amount and purulence of sputum. Side-effects were few and mild.


Oesophageal involvement in bullous pemphigoid. A possible cause of gastrointestinal haemorrhage.

An elderly patient with bullous pemphigoid who had extensive oesophageal bullae is described. The diagnosis was confirmed by routine histopathological examination and immunofluorescence studies. These large oesophageal bullae may have caused massive gastrointestinal haemorrhage in this patient.


Autoimmune granulocytopenia: the detection of granulocyte autoantibodies with the immunofluorescence test.

Neutropenia may be caused by neutrophil autoantibodies. The detection of such antibodies has always been difficult. Recently, we developed a sensitive indirect immunofluorescence technique applicable to granulocytes which proved to be of value in the detection of granulocyte alloantibodies. We have now used this method to investigate the serum and cells of 29 patients with idiopathic or secondary neutropenia. In four patients neutrophil-antigen-specific autoantibodies were detected in the serum and the patient's own granulocytes showed direct fluorescence. Furthermore, differences in the immunoglobulin composition and the temperature of optimal activity of the autoantibodies were found. Direct fluorescence was also demonstrated with the granulocytes from five other neutropenic patients and with the granulocytes from five non-neutropenic patients mainly with infectious disease. However, no granulocyte antibodies could be eluted or shown to be present in the serum. This indicates that a positive direct granulocyte fluorescence test may not be considered as proof that autoantibodies are present.


Lactoferrin content of peripheral blood cells.

The peripheral blood of 60 normal adults was separated into plasma, red cells, neutrophils, lymphocytes, monocytes and platelets. Lactoferrin concentrations were measured in the plasma and cell extracts and compared to those of lysozyme. The neutrophil lactoferrin content in males and post-menopausal females was found to be significantly higher than in pre-menopausal females. A small amount of lactoferrin was found in association with monocytes, but not with lymphocytes, erythrocytes and platelets. Neutrophil lysozyme concentrations did not exhibit any variation with sex and age; but the level in monocytes was higher than that in neutrophils. No correlation was observed between individual neutrophil lactoferrin values and the plasma level. Immunofluorescent studies showed neutrophils to have a lobulated pattern suggestive of nuclear staining. Monocytes did not show direct staining, but exhibited a peripheral pattern after prior exposure to lactoferrin--confirming the existence of a surface receptor. Gel chromatography indicated that neutrophil lactoferrin is in a polymerized or complexed form which elutes with the void volume on Sephadex G-200; serum lactoferrin consists of two forms, one of which also elutes with the void volume on Sephadex G-200.


Platelet-associated coagulation factors: immunological detection and the effect of calcium.

Normal platelets were examined by conventional coagulation methods and specific immunological techniques for the presence of platelet-associated coagulation factors. Platelets washed in buffer containing calcium chloride gave different results form those washed in the absence of calcium. Factor XI was not detected in washed platelets by any technique. Factor II and factor X were removed from platelets by washing in calcium-free buffer but not by calcium-containing buffer. Procoagulant factor VIII was readily removed or inactivated by washing in the presence or absence of calcium, but factor VIII related antigen was consistently demonstrated after multiple washes in either buffer. Factor V activity and antigen was detected in platelet suspensions after multiple washes although the presence of calcium in the washing buffer gave higher factor V assays and stronger immunological reactions than when calcium-free buffer was used. The results are consistent with the presence of calcium dependent binding sites in platelets which may have a role in the enhancement of factor V and phospholipid reactions.


The surface morphology of mitogen-stimulated human peripheral blood lymphocytes.

The changes occurring in surface morphology during the transformation of normal peripheral blood lymphocytes by phytohaemagglutinin (PHA) are described and the surface ultrastructure of the PHA-induced blasts is compared with that of pokeweed mitogen (PWM)-and rabbit anti-beta2-microglobulin antiserum-induced blasts. Both mitogen-specific and non-specific changes were observed and their possible relationship to the activation of lymphocyte subpopulations is discussed. Similar surface characteristics found in various tissue lymphoid cells are also described.


Photochemical cross-linking studies on the interaction of Escherichia coli RNA polymerase with T7 DNA.

We have identified the subunits of Escherichia coli RNA polymerase which are in close contact with the T7 phage DNA template using photochemical cross-linking. In nonspecific T7 DNA-enzyme complexes which occur in all regions of the DNA, subunits sigma, beta, and beta' were cross-linked to the DNA. In contrast, in specific binary complexes which presumably occur at promoter sites, and in the initiation complex (holoenzyme + T7 DNA + initiator dinucleotides + three nucleoside triphosphates), only sigma and beta were cross-linked to DNA, while cross-linking of beta' could not be demonstrated. These results (1) do not support the idea that alpha subunits are involved in the enzyme-template interaction, (2) raise the possibility that sigma subunit participates directly in promoter recognition even though isolated sigma does not bind to DNA, and (3) indicate different modes of interaction between RNA polymerase and DNA in nonspecific and specific complexes. These findings are relevant to the mechanism by which RNA polymerase carries out selective transcription.


Fluorine-19 nuclear magnetic resonance studies of lipid phase transitions in model and biological membranes.

Fluorinated fatty acids of the general formula CH3(CH2)13-mCF2(CH2)m-2COOH are informative spectroscopic probes of the gel to liquid-crystalline phase transitions in phospholipid dispersions and in biological membranes. We present theoretical considerations to suggest that the 19F nuclear magnetic resonance line shapes are very different for frozen and fluid lipid regions. Our studies confirm this expectation for mixed phospholipid multilamellar dispersions containing a trace of difluoromyristate. The method correctly measures the onset and completion temperatures of the transition in the well-studied dimyristoylphosphaditylcholine distearoylphosphatidylcholine system and also describes the motional behavior of the solid and fluid phases within the transition. Lipids extracted from Escherichia coli membranes show similar motional phenomena through the transition-temperature range according to 19F nuclear magnetic resonance studies of difluoromyristate biosynthetically incorporated into the K1060B5 strain, an unsaturated fatty acid auxotroph. Intact cells or membrane vesicles show substantially different behavior from extracted lipids, indicating that membrane proteins significantly perturb the phase transition. Evidence presented in this paper also shows that the 19F resonance from Escherichia coli phospholipids is sensitive to various intramembrane interactions. There is a general decrease in restriction of motion due to neutral lipids and an opposite effect due to the architecture of the native membrane. Neither effect is temperature sensitive. However, there are interactions in the intact membrane, affecting the 19F resonance, that are temperature dependent both due to the phase-transition process and due to processes occurring at high temperatures.


Raman spectra of ten aqueous transfer RNAs and 5S RNA. Conformational comparison with yeast phenylalanine transfer RNA.

Eleven native transfer RNAs have been prepared so as to maintain their Mg2+ content. Their aqueous Raman spectra show a high, relatively constant amount of order in the ribophosphate backbone, as indicated by the ratio 1.73 +/- 0.05 for I814/I1100 in all samples. Variation in the effectiveness of stacking of guanine and adenine bases is seen, though most of the transfer RNAs studied have a comparable degree of stacking to that found in phenylalanine transfer RNA from yeast, whose tertiary structure has been determined by X-ray crystallography. The spectrum of Escherichia coli 5S RNA indicates that the stacking efficiency of the guanine bases is much higher in 5S RNA than in yeast in phenylalanine transfer RNA, while that of the adenine bases is lower.


Studies of the effects of ultraviolet radiation on the structural integrities of ribosomal RNA components of the Escherichia coli 50S ribosomal subunit.

The effects of 254-nm radiation on the structural integrities of free and 50S ribosome-bound 5S and 23S ribosomal ribonucleic acids (rRNA) have been elucidated. Irradiation of aqueous solutions of Escherichia coli 50S ribosomes with 253.7-nm radiation results in the formation of single-strand breaks in double-stranded regions of the 23S rRNA component, but not in rRNA chain scission, and destabilization of the secondary structure of the 23S rRNA toward denaturation. The minimum doses of 253.7-nm radiation required for the first detection of the two effects are 7 x 10(19) quanta for the production of single-strand breaks in double-stranded regions of the 23S rRNA, and less than 2.3 x 10(19) quanta for destabilization of the 23S rRNA secondary structure. Free 23S rRNA is resistant toward photoinduced chain breakage at doses of 253.7-nm radiation up to at least 2.3 x 10(20) and is much less sensitive toward destabilization of secondary structure than ribosome-bound 23S rRNA toward chain breakage, 50S ribosome-bound 5S rRNA is resistant toward chain breakage at doses of 253.7-nm radiation up to at least 2.3 x 10(20) quanta. Ribosome-bound 5S and 23S rRNA are also not photosensitive toward intermolecular 5S/23S rRNA crosslinkage.


Yeast inner histones and the evolutionary conservation of histone-histone interactions.

The inner histones of the yeast, Saccharomyces cerevisiae, have been isolated and identified by their amino acid compositions. H4 appears to be close to its calf and pea counterparts. H2a, H2b, and H3 have diverged. The isolation of the histones was accomplished by consecutive slab-gel fractionation, and a number of novel features of the method are described. These appear to be generally useful for preparing many types of protein. The binding pattern of the yeast inner histones is identical to the binding pattern for calf and for pea histones. Data on interspecies complexing indicate that the surfaces across which the histones interact are very highly conserved.


Stable isotope studies on the biosynthesis of the thiazole moiety of thiamin in Escherichia coli.

Deuterated and 13C-labeled sugars were fed to Escherichia coli growing on defined medium. The position and extent of incorporation of the label into the 4-methyl-5-beta-hydroxyethylthiazole portion of thiamin and other cellular components were measured by gas chromatography-mass spectrometry. Based on the findings, it is concluded that the contiguous five-carbon unit of the 4-methyl-5-beta-hydroxyethylthiazole is biosynthetically derived from pyruvate and a triose phosphate.


Ionic strength perturbation kinetics of gene 32 protein dissociation from its complex with single-stranded DNA.

Equilibrium and kinetic studies of the interaction of gene 32 protein of T4 phage with single-stranded fd DNA were performed monitoring the changes in protein fluorescence. From the fluorescence titrations, it was estimated that a monomer of gene 32 protein covered six nucleotide bases on the DNA and the lower limit for the apparent association constant was 1.9 x 10(8) M-1 with a cooperative parameter of 10(3) in 0.1 M 2-amino-2-hydroxymethyl-1,3-propanediol hydrochloride (pH 7) at 25 degrees C. When an ionic strength jump was applied to the gene 32 protein-fd DNA complex using a stopped-flow apparatus, the complex underwent a dissociation into its individual components accompanied by an increase in protein fluorescence. The kinetics of the dissociation are not consistent with a single first-order process. The data, however, can be analyzed in terms of a model in which gene 32 protein molecules release cooperatively starting from either one or both ends of a cluster of proteins bound to fd DNA. This type of dissociation of gene 32 protein from single-stranded DNA is very efficient and has interesting implications: it could provide a way to facilitate a rapid "zippering" of the two complementary DNA strands during DNA replication and genetic recombination.


Yeast phenylalanyl-tRNA synthetase. Properties of the histidyl residues.

Reactivity of the histidyl groups of yeast phenylalanyl-tRNA synthetase was studied in the absence or presence of substrates. In the absence of substrates about 10 histidine residues were found to react with similar kinetic constants. Phenylalanine at 10(-3) M was found to protect two histidyl residues; increasing the amino acid concentration to 5 . 10(-3) M resulted in the protection of two more histidyl groups. tRNAPhe did not afford any protection to histidine residues, but acylated phenylalanyl-tRNA (Phe-tRNAPhe) protected two of the four histidyl groups already protected by phenylalanine. These results suggest the existence of two different sets of accepting sites for phenylalanine: one specific for the free amino acid, the other one specific for the amino acid linked to the tRNA, but being accessible to free phenylalanine, with a somewhat lower binding constant, ATP was found to mask around four histidyl residues against diethylpyrocarbonate modification. By photoirradiation of enzyme-phenylalanine complex in the presence of rose bengale, a significant amount of amino acid was bound to the alpha subunit (Mr = 73 000) of phenylalanyl-tRNA synthetase, confirming that the amino acid binding site is located on this subunit, as previously suggested by modification of thiol groups. Upon irradiation of an enzyme-tRNA complex, almost no covalent binding of tRNA occurred during enzyme inactivation, suggesting that the histidyl residues involved in the enzymic activity are not required for tRNA binding.


Codon-specific interaction of uncharged transfer-RNA with eukaryotic ribosomes.

Rat liver ribosomes bound [32P]tRNAPhe in both a codon-dependent and codon-independent manner. The codon-dependent binding was studied further by utilising the ability of the unchanged tRNAPhe to inhibit the poly(U)-directed binding of [3H]Phe-tRNA to ribosomes. At least part of the codon-dependent binding of uncharged tRNA appears to be to the ribosomal A-site.


Study of a haploid yeast strain with an unusually high rDNA content. III. Unequal meiotic segregation of the gamma-DNA fraction.

DNA from different strains of Saccharomyces cerevisiae has been fractionated in preparative Ag+/Cs2-SO4 density gradients. The results show that there are real differences in amount of the nuclear satellite component, the gamma-DNA, from one strain to the other. The gamma-DNA forms a homogeneous dense band that contains all the rDNA, and the amount of gamma-DNA estimated from the gradients can be correlated to amount of rDNA derived from rRNA-DNA hybridizations. By various crossings and sporulations we have obtained diploid and haploid strains with gamma-DNA contents ranging from 7 to 20% of the nuclear DNA. During meiosis, the amount of gamma-DNA appears to segregate in a pattern that indicates unequal crossing over as a possible mechanism for differences in gamma-DNA contents.


Formation of 3-hexaprenyl-4-hydroxybenzoate by matrix-free mitochondrial membrane-rich preparations of yeast.

It has been shown that a 10 000 x g matrix-free mitochondrial membrane-rich preparation from commercial bakers' yeast is able to synthesize 3-all-transhexaprenyl-4-hydroxybenzoate from 4-hydroxybenzoate and isopentenyl pyrophosphate. The synthesis is Mg2+ dependent and is stimulated markedly by the primer for polyprenylpyrophosphate synthesis of 3-hexaprenyl-4-hydroxybenzoate from 4-hydroxybenzoate, isopentenyl pyrophosphate and 3,3-dimethylallyl pyrophosphate the priming function of 3,3-dimethylallyl pyrophosphate can be performed by either geranyl pyrophosphate (most efficient) or farnesyl pyrophosphate. At high Mg2+ concentrations, however, geranyl pyrophosphate and farnesyl pyrophosphate act mainly as sources of preformed side chains and 3-diprenyl- and 3-tripenyl-4-hydroxybenzoate, respectively, are produced. In the presence of a source of preformed polyprenyl pyrophosphates the membrane preparations catalysed the polyprenylation of methyl-4-hydroxybenzoate, 4-hydroxybenzaldehyde, 4-hydroxybenzylalcohol and 4-hydroxycinnamate. No evidence was obtained for the involvement of either 4-hydroxybenzoyl CoA or 4-hydroxybenzoyl-S-protein in the formation of 3-polyprenyl-4-hydroxybenzoates.


Role of chelation and water binding of calcium in dormancy and heat resistance of bacterial endospores.

The possible relationship between the water binding by bacterial endospores and their dormancy and heat resistances has been examined in terms of the coordination characteristics of the spore-bound calcium. Stabilities of the calcium complexes of typical cytoplasmic and structural spore components were determined by potentiometric equilibrium pH measurements in model systems consisting of DPA, glycine, alanine, glutamic acid, alanyl-glutamic acid, triglycine, and tetraglycine. The Ca++-form and H+-form spores of Clostridium botulinum 33A were investigated in vivo with respect to their water sorption and heat-resistance characteristics. The results suggest that the complexing of calcium and Ca(II)-DPA may be biologically significant for spore resistance and dormancy at the following three levels: (1) complexing with spore cytoplasmic pool constituents consistent with the idea of a metal-chelate cross-linked cytoplasm or spore cement stabilizing the essential biological macromolecules, (2) complexing with structural components of the spore as indicated by the interaction with model peptides, and (3) coordination with water to produce an apparently dehydrated environment in the spore as evident from the much greater water-sorption capacity of the Ca++-form spores vs the much smaller water sorption of the H+-form spores. Interestingly enough, DPA itself, in the absence of metal ion, showed some interaction with di-, tri-, and tetrapeptides and a weak but detectable interaction with amino acids. Although the exact mode of the DPA-peptide interaction is not clear, it is attractive to speculate about its possible involvement in the control of spore dormancy and resistance.


[Study of the methylation process and DNA methylase specificity in Shigella].

The nature and content of minor bases in DNA of 3 Shigella strains are investigated. DNAs from Shigella stutzeri 2, Sh. sonnei 1188 and Sh. sonnei 311 are found to contain 0.43, 0.56 and 0.45 mol.% of N6-methyladenine respectively. 5-methylcytosine (0.16 mol.%) is discovered in Sh. sonnei 311. Substrate specificity of adenine methylase from Sh. sonnei 1188 with respect to phage DNAs of different host modification is investigated. Recognition sites for guanine methylase of DDVI phage and for adenine methylase of Sh. sonnei 1188 turned to be different. DNA of DDII phage grown in Sh. stutzeri 2 cells does not accept methyl groups under the treatment with Sh. sonnei 1188 extracts, but it is methylated by Escherichia coli extract. Adenine methylases of Sh. sonnei 1188 and Sh. stutzeri 2 are suggested to be either the same enzyme, or enzymes, which recognition sites are partially overlapped.


Positive end expiratory pressure: effects on lung mechanics of premature lambs.

Pulmonary mechanics were determined at 0, 3, 6, and 10 cm H2O positive and expiratory pressure (PEEP) in premature lambs at a mean gestational age of 134 days. Functional residual capacity increased (p less than 0.005) by 7% (1.6 ml/kg) per cm H2O PEEP. Dynamic lung compliance and specific compliance significantly decreased by 10% (0.11 ml/cm H2O/kg) and 9% (0.0051 l/cm H2O) per cm H2O PEEP, respectively, for PEEP above 3 cm H2O level. Inspiratory lung resistance increased significantly (p less than 0.05) only between 0 and 6 cm H2O PEEP while expiratory lung resistance increased (p less than 0.05) between 0 cm H2O PEEP and all higher levels. The data suggest that PEEP in excess of 3 cm H2O produces undesirable effects on lung mechanics in premature lambs. These results may be important in predicting contraindications and potential complications of positive pressure breathing in the newborn.


Development of glucose-mediated insulin release response in organ cultured rat pancreas.

In the Sprague-Dawley rat, glucose concentration dependent insulin release first appears 2 days after birth. If pancreatic explants from 19-, 20- or 21-day fetal rats are organ cultured to a period corresponding to the 4th postnatal day, 120 min stimulus with glucose (100 or 300 mg/dl) fails to produce glucose-dependent insulin release. When explants from 20-day fetal pancreas are cultured, glucose-mediated insulin release develops after 12 h to 2 days of culture, and persists for up to 2 days. Explants from 3 day postnatal pancreas retain glucose-dependent insulin release for at least 2 days culture. High tissue insulin levels and continued release of immunoreactive insulin into culture medium are maintained throughout the culture period studied. Our data show that glucose-mediated insulin release can develop in organ culture, and suggest that this development, after the 19th fetal day, does not require extrapancreatic neural or endocrine factors.


[Diffusion of water through the narrow pores of biomembranes].

The pulsed-gradient, nuclear magnetic resonance method has been used to study diffusion of water through the cell membranes. An analytical expression is derived for relative amplitude of nuclear spin-echo, describing the diffusion of water in membrane pores. The latter are so narrow, that their diameter is only a little greater than the water molecule diameter. The experimental data for consumed yeast with normal content of water agree well with the theoretical dependence.


[Immunohistochemical study of cardiolipin and phosphatidylinositol in mouse liver].

Localization of two phospholipid haptens--cardiolipin and phosphatidylinositol--in mouse liver sections was studied by the indirect method of fluorescent antibodies. Two types of liver sections--paraffin and cryostat, and two type of fixation--in acetone, and in the acetone, buffer, and formalin mixture--were used. Antiphospholipid sera stain specifically the plasma membrane of hepatocytes and predominantly the membrane region overlooking the blood capillary. A possibility of detecting the specific phospholipid haptens depends on the method of obtaining the sections and their fixation. Two types of immunization give two types of antiphospholipid sera which differ by the stability, by the possibility of monospecific antibodies isolation from them on lipid immunosorbents, and by the types of liver section staining.


Conformational prediction and circular dichroism studies on ribosomal protein S4 from Escherichia coli.

The conformation of ribosomal protein S4 from Escherichia coli has been studied by circular dichroism (CD) and shown to possess unique conformation free in solution. The near ultraviolet spectrum suggests the existence of unique tertiary structural environment for the aromatic amino acid residues. The far ultraviolet spectrum gives an estimation of its secondary structure which is 32% alpha-helix and 14% beta-structure in reconstitution buffer at 25 degrees C. The conformation of S4 has been predicted from its sequence, and two models are presented here. An attempt is made to correlate these two molecular models with the available physicochemical data concerning the shape, conformation, and possible RNA binding site of protein S4.


[Nonspecific resistance in germ-free and E. coli monocontaminated miniature piglets].

Phagocytic activity of leukocytes, as well as the complement, properdin, and lysozyme levels in the blood serum of miniature piglets, germfree and monocontaminated with E. coli 055 and E. coli 083, were studied. E. coli 055 phagocytosis was decreased in the presence of autologous serum and complement and increased under the effect of specific opsonins (antibodies to E. coli 055). Complement, properdin, and lysozyme levels were decreased in the germfree, in comparison with conventional animals. In the E. coli contaminated piglets properdin and complement production was stimulated most, and lysozyme formation--less. No antibodies to E. coli 055 were revealed in monocontaminated piglets. The highest lysozyme levels were found in the ex-germfree animals, this indicating the participation of factors other than E. coli contamination in lysozyme stimulation. It is concluded that microbial contamination played an important role in the development of cellular and humoral factors of the organism resistance.


[Effect of stem cell inhibition factor and macrophage inhibition factor on mouse spleen cell exocolonization and migration].

The migration activity of the spleen cells from intact mice is inhibited by the stem cell inhibitory factor (SCIF) released by lymphocytes treated with antilymphocytic globulin. The degree of the migration inhibition is proportional to the activity of SCIF in the colony-formation inhibition. The macrophage-migration inhibitory factor (MIF), obtained in the H-2 system exhibited a stimulating effect on the colony formation in mice when used in vitro for the treatment of bone marrow transplants. This activity of MIF corresponds to its migration-inhibitory effect on the spleen cells. Incubation of the bone marrow cells with MIF for 30 minutes is more effective than the 2-hour treatment. The observed effects are interpreted as an indication of non-identity of SCIF and MIF.


Banding studies on chromosomes in diffuse "histiocytic" lymphomas: correlation of 14q+ marker chromosome with cytology.

Chromosomes were studied in cells from tissues primarily involved by diffuse "histiocytic" lymphoma in nine patients. Two of the patients had stage II disease; their tumors were fibrotic and had no mitotic cells. One patient was in stage III, and the remaining six patients had stage IV disease. The modal chromosome number of abnormal cells from these last seven patients was hypodiploid in two, hyperdiploid in four, and near-triploid in one. Complete banding studies of six cases and partial analysis of the seventh indicate that (1) every patient had a distinct cell line with common markers, with a few cells showing minor variants; (2) although certain chromosomes (Nos. 1, 2, 3, 9, 12, and 14) were structurally affected more often than others, no markers with the same banding pattern were noted among them; and (3) the cytologic type of lymphoma could be correlated with the karyotype in all seven patients. When the Lukes and Collins classification was used, three patients whose tumors were composed predominantly of large noncleaved cells showed a 14q translocation leading to the formation of a 14q+ marker chromosome. This marker was not observed in four patients whose tumors had a majority of large cleaved cells. These preliminary results, if confirmed in a larger series of patients, will provide additional evidence that there are consistent chromosome changes associated with specific subtypes of lymphoproliferative disorders analogous to the Ph1 chromosome in chronic myelogenous leukemia.


Carrageenan and the immune response.

Since the biological effects of carrageenan were reviewed in 1972 by Di Rosa it has become clear from a large number of reports that this algal polysaccharide markedly influences immune responses. Profound suppression of immunity evidenced by impaired antibody production, graft rejection, delayed hypersensitivity and anti-tumour immunity, has been observed in carrageenan-treated animals and the immunodepressive ability of carrageenan confirmed by in vitro studies. Efforts at analysis of carrageenan-induced immune suppression have focussed on the selective cytotoxic effect of this agent on mononuclear phagocytes. Faith in the ability of carrageenan to eliminate those cells has led to its use in examination of the role played by mononuclear phagocytes in various aspects of immune reactivity. This review documents and discusses the effects of carrageenan on immune responses and assesses the value of carrageenan as a useful tool in both current and future work aimed at broadening our knowledge of mechanisms underlying immune reactions.


Monocyte production in Hodgkin's disease and non-Hodgkin's lymphoma.

Monocytopoietic proliferation activity was investigated in patients with untreated Hodgkin's disease, Hodgkin's disease in long-term complete remission, and untreated non-Hodgkin's lymphoma of the lymphosarcoma and reticulosarcoma type. Untreated Hodgkin's disease was found to be associated with a rise in medullary monocyte production which returned to normal during long-term complete remissions. In contrast, monocyte production was increased in only 5 out of 14 patients with lymphosarcoma and reticulum cell sarcoma, normal in 3, and reduced in 6. In neither of these lymphomas was any relation between monocyte production and stage or histology of the disease detectable.


[Chemotherapy of malignant melanoma. Results of a controlled clinical trial comparing vincristine + dacarbazin (DTIC) with and without duborimycin (author's transl)].

Adding duborimycin to the association of vincristine + DTIC in the treatment of malignant melanoma produces therapeutic results interesting but not statistically significant and not counter-balancing the toxic side effects. This study confirms the lack of positive results of polychemotherapy in melanoma as compared to treatment by an efficacious single drug therapy (DTIC); it also emphasizes the necessity of randomized studies so that valuable comparisons may be done.


Role of diet and nutrition in cancer cause, prevention and treatment.

The roles of diet and nutrition as etiologic factors in cancer incidence is discussed. Diet and nutrition have recently been recognized as causative agents in other chronic diseases. Epidemiologic evidence supportive of the hypothesis that different diets rather than other environmental contaminants are important in the causation of certain forms of cancer is reviewed, including studies on several migrant populations and ethnic groups. Specific dietary components have been correlated with certain forms of cancer, such as bowel cancer and fat consumption, and a theory of the mechanism is set forth. The animal studies discussed strongly confirm the results of epidemiologic studies in man. Additionally, nutrition's important role in cancer therapy and rehabilitation is described. A variety of intervention techniques are available to maintain the nutrition status of the cancer patient. Finally, the research priorities and the Diet, Nutrition and Cancer Program (DNCP) of the National Cancer Institute are explained.


[Genetic factors in the etiology of breast cancer (author's transl)].

A review of literature shows that, at present, genetic factors are difficult to distinguish from environmental factors. A number of studies have put into light relationships between factors tranmetted genetically and an increased risk of breast cancer in some women. This might be a reflect of the transmission of a certain susceptibility. However, one of these factors alone cannot explain the increase of the risk. Most likely, as for many types of cancers, the development of breast cancer is due both to a multigenic transmission of a certain susceptibility and to the action of environmental factors. Though, epidemiological studies make possible to identify a high risk population. A regular follow-up of this population would permit early diagnosis and possibly prophylactic measures concerning the known environmental factors, and in particular hormonal factors.


[Mendelian genetics and cancer (author's transl)].

Two hundred different mendelian genes can have a cancerogenic effect in man, but it is difficult to make out between the genetic and the environmental part. Acute lymphoblastic leukemia is an example that the actual cancerogenic factor can be environmental and not genetic. Genetically controlled tumors can result from two successive mutations, the first being in some cases prezygotic. The first genetic accident can be a birth defect or a chromosomic fragility syndrome. The histocompatibility major system can play a role in the frequence and in the evolutive type of some cancers. The most frequent hereditary syndromes which can be associated with cancers are quoted here.


Changes in blood flow and mediator content of rabbit skin grafts.

1. Blood flow changes have been measured in rabbit skin homografts and autografts and an attempt has been made to correlate these changes with the presence of vasoactive agents in homogenates of the grafts. 2. During the healing-in of both types of grafts the blood flow and histamine content increased. 3. If this histamine was responsible for the vasodilatation via an H2-receptor it must have been released in the form of "nascent" or intrinsic histamine since the vasodilatation was not antagonized by antihistamine. 4. A peak of histamine concentration occurred in homografts, more than three times that in autografts at the onset of rejection. At the same time the blood flow stopped completely. 5. This vasoconstriction might be mediated by histamine since treatment with mepyramine delayed the cessation of blood flow from 5 days up to 7 to 10 days. 6. Prostaglandins appeared to be involved only in the period of peak blood flow in homografts because indomethacin did not delay the onset of rejection, but reduced the peak blood flow in the homografts at a time when there was an increased content of prostaglandin E2 in the homograft tissue.


Obsessive thoughts: the problem of therapy.

Eleven patients with obsessive thoughts were treated in two pilot studies. In the first of these patients were given thought-stopping, and this was contrasted with relaxation therapy. In the second study patients were treated by a technique described here as 'satiation', and this was followed by thought-stopping and finally a course of amitriptyline. The overall results were poor, but one type of obsessive thought responded well to satiation.


Mianserin and lithium in the prophylaxis of depression.

Forty-one out-patients with a history of at least three attacks of depressive illness were randomly allocated to treatment on a double-blind basis for one year with either mianserin 20 mg three times daily plus placebo lithium tablets, or to lithium tablets once daily plus placebo mianserin tablets. After one year, the dosage of mianserin was increased to 30 mg t.d.s. for a further six months. All but three of the patients had previously been stabilized on prophylactic lithium therapy. Lithium was found to be significantly superior to mianserin in avoiding admission to hospital or ECT. The overall affective morbidity index, calculated from global rating, showed no significant difference between drugs, but the index of the mianserin group was higher in the second six months than in the first. The lithium group showed no such change. Lithium remains the choice for the prophylaxis of unipolar recurrent depressive illness.


Randomized multicentre trial of oral bowel preparation and antimicrobials for elective colorectal operations.

A study of 120 patients undergoing elective colorectal operations has investigated the effect of adding oral neomycin and metronidazole to bowel preparation in a double-blind randomized controlled trial. Comparisons have also been made between a standard mechanical preparation and the use of an elemental diet. The addition of neomycin and metronidazole to bowel preparation significantly reduced the rate of wound sepsis (P less than 0.01), septicaemia (P less than 0.02) and anastomotic dehiscence (P less than 0.02); anaerobic infections were abolished and there was a significant reduction in the incidence of aerobic Gram-negative infections. Elemental diets were shown to have no advantage over mechanical preparation.


A comparison of noxythiolin and povidone-iodine in experimentally induced peritoneal infection in mice.

Noxythiolin (Noxyflex, Geistlich), given intraperitoneally as a 2.5 per cent solution, protected mice from the lethal effects of an intraperitoneal injection of Escherichia coli. Povidone-iodine (Pevidine, Berk), containing 0.075 per cent iodine, gave no protection.


Results of a controlled randomized trial of proximal gastric vagotomy with and without pyloroplasty.

The 1--5 year results of a prospective randomized trial of proximal gastric vagotomy (PGV) with and without pyloroplasty in 64 men operated upon electively for chronic duodenal ulcer are reported. The effects of the operation on gastric secretion, as tested at 6 months with pentagastrin and isulin, were the same in both groups. There was no statistically significant difference in the clinical results between the two groups. The authors conclude that the addition of pyloroplasty makes little, if any, difference to the results of PGV. Pyloroplasty is thus better omitted as it adds nothing of value and may increase the risk of the procedure.


Haemostatic defect in non-immune patients with falciparum malaria: no evidence of diffuse intravascular coagulation.

Nine non-immune patients with imported falciparum malaria were examined for signs of diffuse intravascular coagulation (DIC). Although all had thrombocytopenia initially and some later had a decline in plasma fibrinogen concentrations, DIC was never detected, even in severely affected patients with coma and kidney damage. None of the patients were given heparin and all recovered without residual symptoms. Heparin administration should probably be considered only when clear-cut DIC, which possibly never occurs in falciparum malaria, has been demonstrated.


Beclomethasone dipropionate dry-powder inhalation compared with conventional aerosol in chronic asthma.

In a double-blind study beclomethasone dipropionate inhaled as a dry powder in doses of 100 microgram four times daily and 150 microgram four times daily was compared with the conventional aerosol dose of 100 microgram four times daily in 20 outpatients with chronic asthma. Each of the three treatments was given for four weeks. The dry powder in a dose of 150 microgram four times daily had advantages over the other two treatments in terms of FEV1 and the number of exacerbations of asthma during the study. There were no adverse reactions to inhaling dry-powder beclomethasone. It was concluded that this new way of administering the drug was effective in chronic asthma, and should allow most patients with chronic asthma who cannot use conventional pressurised aerosols efficiently to benefit from inhaled corticosteroid treatment.


Two types of febrile seizure: anoxic (syncopal) and epileptic mechanisms differentiated by oculocardiac reflex.

The duration of cardiac asystole induced by ocular compression was measured in 100 consecutive children referred for electroencephalographic examination after one or more febrile convulsions (FC). The children were classified into three groups-namely, those with anoxic FCs, those with epileptic FCs, and "others"-according to the appearances of the FC and the electroencephalogram (EEG). In 14 children the description of the FC suggested non-epileptic anoxic cerebral seizures such as are seen after prolonged syncope or breath-holding. In 35 children the FCs were assumed to be epileptic in mechanism on the basis of unilateral (hemiclonic) twitching, known cerebral disease, a family history of epilepsy, or spikes on the EEG. In the 51 "others" the FCs could not be classified. Definitely abnormal asystole (four seconds or over) was induced by ocular compression in half the anoxic group, in 16% of the "others," but in none of the epileptic group. The differences between the degree of asystole induced in each of the three groups was highly significant (P=0.005).These results support the hypothesis that vagal-mediated cerebral ischaemic anoxia is implicated in the genesis of FCs that resemble anoxic seizures and in a substantial number of those without an obvious epileptic mechanism. The significance, genetics, management, and prognosis of FCs must now be re-examined in this light.


Effects of varying radiation schedule, cyclophosphamide treatment, and duration of treatment in acute lymphoblastic leukaemia. Report to the Medical Research Council by the Working Party on Leukaemia in Childhood.

In a multicentre trial of treatment for acute lymphoblastic leukaemia the effects of three types of central nervous system prophylaxis, the inclusion of cyclophosphamide, and the total duration of chemotherapy were assessed. A schedule with a high dose of spinal irradiation (2400 rads) without intrathecal methotrexate was inferior to schedules with some (1000 rads) or no spinal irradiation but with intrathecal methotrexate. The addition of cyclophosphamide 600 mg/m2 given intravenously every 12 weeks was of no benefit and was possibly deleterious. There was no advantage in adding four 12-week courses of chemotherapy after eight courses (total duration two years) had been given. Girls fared significantly better than boys, the difference being only partly due to the occurrence of testicular relapse.


Respiratory syncytial virus infection: admissions to hospital in industrial, urban, and rural areas. Report to the Medical Research Council Subcommittee on Respiratory Syncytial Virus Vaccines.

A collaborative study of 10 centres during the winters of 1973-4 and 1974-5 showed that respiratory syncytial virus (RSV) was the major cause of admission to hospital for respiratory disease in children under 5 years of age in industrial, urban, and rural communities. In all areas the distribution of clinical symptoms and their severity was similar, but the rate of admission in relation to population was over twice as high in industrial as in other areas. The maximum yearly admission rate occurred among infants aged 1 to 3 months: 24.5 per 1000 of that age group were admitted to hospital. Two methods of diagnosing RSV infection--virus isolation and immunofluorescence from postnasal aspirates--were compared, and the two methods were found to agree in 91% of cases. The results of this study confirmed the importance of RSV as a respiratory pathogen in young children. Further studies are needed to determine how the virus produces its effects and to develop preventive measures.


A double-blind study on the effects of butorphanol compared with morphine in balanced anaesthesia.

In a randomized double-blind trial a total of 50 consenting patients scheduled for elective surgical operations were given multiple intravenous doses of butorphanol tartrate or morphine sulphate in combination with other agents to evaluate and compare the efficacy of these drugs in balanced anaesthesia. Equipotent doses of butorphanol tartrate (mean dose 2.0 mg) or morphine sulphate (10 mg) and thiopentone were employed as induction agents followed by the standardized use of muscle relaxants to facilitate tracheal intubation. Butorphanol tartrate or morphine sulphate were then employed during maintenance of anaesthesia in repeated intravenous doses, averaging butorphanol 4.6 mg and morphine 22.8 mg per patient. Evaluation of anaesthesia showed that induction and course were smooth in 96 per cent of the patients receiving butorphanol tartrate and in 84 per cent of patients receiving morphine sulphate. The analgesic action of butorphanol appeared in every respect to approximate that of morphine sulphate, with negligible side-effects. The data demonstrate that butorphanol is a useful analgesic for use in a balanced anaesthesia technique with a low side-effect incidence.


A double-blind comparison of butorphanol and meperidine in labour: maternal pain relief and effect on the newborn.

Butorphanol tartrate 1 mg and 2 mg were compared in 80 normal mothers at term in a double-blind study with meperidine hydrochloride 40 mg and 80 mg for the relief of pain in labour. Butorphanol was found to be as effective as meperidine in relieving pain in labour. The foetal condition, as measured by ECG monitoring, Apgar scores, time to sustained respiration, umbilical venous H+ (pH) and PCO2, and a general nursery survey were comparable for meperidine and butorphanol. No psychomimetic phenomena were seen. Assays indicated that both butorphanol and meperidine crossed the placenta. The mean concentration of butorphanol in neonatal serum was 0.84 times maternal serum at 1.5 to 3.5 hours after intramuscular administration of a single or two successive doses of butorphanol 1 mg or 2 mg to the mother. The mean concentrations for meperidine in neonatal serum was 0.89 times maternal serum at 0.85 to 3.6 hours after intramuscular administration of meperidine 40 mg or 80 mg to the mother. Neither analgesic caused severe depression of the infant except for one meperidine-treated case.


Double-blind comparison of the neurobehaviour of neonates following the administration of different doses of meperidine to the mother.

The Early Neonatal Neurobehavioural Scale (E.N.N.S.) tests, first described by Scanlon, et al.1 were administered to 920 neonates on the first and second days of life. Meperidine was not given to 389 mothers, 50 mg was given to 358 mothers and 75 to 150 mg to 173 mothers within four hours of delivery. The delivery was conducted under chloroprocaine epidural anaesthesia in 280, ketamine-nitrous oxide general anaesthesia in 180, thiopentone-nitrous oxide general anaesthesia in 180 and lidocaine pudendal block in 280. All babies were over 2500 grams in weight with an Apgar score of at least 8 at one minute and 10 at five minutes. All were delivered from healthy women 18 to 35 years of age following a normal labour. The evaluator was unaware of the anaesthetic management, the method of delivery or the perinatal risk factors. There was no significant difference between the mothers and babies in the three meperidine dosage groups for maternal parity, maternal age, birth weight, number of forceps deliveries or duration of labour. Administration of meperidine was associated with a broad spectrum depression of most items on the E.N.N.S. on both the first and second days of life. The depression was greatest with the highest dose of meperidine. The depression produced by anaesthetic agents and meperidine were additive and the highest scores on this scale were obtained in those babies delivered under chloroprocaine epidural anaesthesia without meperidine.


Balanced regional analgesia--an hypothesis.

An hypothesis is advanced, based upon observation of patients undergoing selected types of regional analgesic blocks, that total patient care during any regional analgesic technique consists of maintaining a balance of local analgesia, tranquillity and the use of a centrally acting analgesic. The latter is required to relieve non-specific distress unrelated to the operation which appears to be caused by a disturbance of sensory input to the cerebral cortex, possibly the proprioceptive input. A small group of patients will not respond to any sedation accompanying regional analgesia and need general anaesthesia. It is suggested that failure to appreciate all three parts of this triad may contribute to uncertainty of patient control during regional block.


Are serum antibody, complement or K-cell dependent cellular cytotoxicity involved in corneal graft rejection?

Having shown that complement independent cellular cytotoxicity (CICC) plays a part in destroying the donor cell we wished to see if serum antibody cytotoxicity (SAC), complement dependent cellular cytotoxicity (CDCC) or K-cell mediated cellular cytotoxicity (KCC) might not also be involved in the rejection of corneal grafts. Rabbits were grafted with allo- and xenogreneic corneas. At various times, lymphoid cells and sera were collected from a recipient and a control animal. The donor's corneal cells and those of the control animal were cultivated in vitro, and then labelled with 51chromium. The recipient and control lymphoid cells and sera and/or complement were mixed with the labelled cells. A 51chromium release assay was done after incubation. The test was negative for SAC, CDCC, and KCC and we feel that they have no major part in the rejection of corneal grafts.


The predictive value of leucocyte migration inhibition test in human keratoplasty.

We compared the results of penetrating keratoplasty in 18 patients whose preoperative or immediate postoperative leucocyte migration inhibition (LMI) tests were positive (greater than 20% inhibition) with those in 15 patients whose LMI tests were negative. A negative LMI test indicated a greater chance of avoiding graft rejection (P less than 0.005), and of ending up with a clear graft (P less than 0.05).


Evaluation of an automated method for analysing the electromyogram.

An automated system, incorporating the ANOPS-101 mini-computer, has been used to analyse the EMG. The vastus medialis (VM) and biceps brachii (BB) muscles were studied in 28 controls, 16 patients with myopathies, and in 26 patients with denervating disorders. For each muscle mean values were computed for the durations and numbers of phases of muscle action potentials; the mean density and amplitude of the deflections in the interference pattern were also measured. A higher incidence of abnormalities could be detected in myopathic than in neuropathic disorders; for both conditions the incidence was significantly greater in BB than in VM. For the diagnosis of denervation the most useful measurement was that of potential duration; for the detection of myopathies amplitude determinations were also very useful. The present results have been compared with those of other published studies in which automatic EMG analysis has been employed.


Computerized assessment of memory performance in dementia.

Memory deficits in demented patients were studied by applying a computerized system to titrate individual memory performance. Two delayed matching to sample tasks were used. ABA1 involved random visual shapes used as a measure of visual memory. ABA2 involved nonsense syllable trigrams used as a measure of verbal memory. A Human Test System panel with a display screen was utilized. This screen was a rear view projection window divided into four independent 3 X 2 sections arranged in a 2 X 2 matrix. The sample stimulus appeared on the upper left window for one second. The delay interval between stimulus sample and choices varied by 7 seconds dependent upon patient performance per trial. Also utilized was a color distractor task. Task parameters, data acquisition, retrieval, and graphic print-outs were all computerized. Individual titration levels reflected the severity of neurological impairment. Computerized assessment enabled subtle changes in memory performance to be readily identified. Implications for use of the system as a screening device in the assessment of mental changes in the elderly are apparent.


Internal carotid artery embolism by shotgun pellet.

Various examples of foreign body embolization of cerebral arteries, usually followed by serious consequences, have been reported (Lindberg et al., 1961; Chason et al., 1963; Steele et al., 1972; Wetli et al., 1972). However, a shotgun pellet entering the left atrium of the heart through a gunshot wound of the chest with subsequent embolic occlusion of one of the carotid arteries appears to be unique. It is the subject of this short communication.


Improvement of in vitro mitogen proliferative responses in non-Hodgkin's lymphoma patients exposed to fractionated total body irradiation.

Patients with non-Hodgkin's lymphomas who failed to respond to chemotherapy were treated with low dose fractionated total body irradiation (TBI). Prior to during and after scheduled therapy, their clinical status was evaluated and peripheral blood studies were performed to enumerate EAC and E rosetting cells and to measure proliferative responses to mitogens. Peripheral blood abnormalities were present prior to TBI using these in vitro assays. Patients who obtained clinical remissions following therapy had restoration of mitogen progressive disease had no change in their ability to proliferate in response to mitogens. Normalization of EAC and E rosetting profiles often occurred regardless of clinical response. These data indicate that low dose fractionated TBI produces clinical and in vitro detectable immunological changes. Furthermore, they show that improvement in mitogen responsiveness correlates best with good clinical responses.


5FU infusion with mitomycin-C versus 5 FU infusion with methyl-CCNU in the treatment of advanced colon cancer: a Southwest Oncology Group Study.

The Southwest Oncology Group (SWOG) in a randomized trial evaluated 5FU infusions in combination with either Mitomycin-C or Methyl-CCNU in patients with disseminated large bowel cancer. A response rate of 18% was noted on the 5FU-Mitomycin limb as compared to 16% on the Methyl-CCNU arm (p = .39). Median survival for all treated patients was 43 weeks on both arms. Myelosuppression was found to be more significant on the Mitomycin-C arm. Regression analysis demonstrated that performance status, sex, and primary site were significant pretreatment characteristics for predicting survival. The response rates associated with this burdensome method of 5FU administration in combination with either Mitomycin-C or Methyl-CCNU appear to offer little advantage over bolus 5FU alone.


Pulmonary histopathologic changes associated with melphalan therapy.

A case of fatal pulmonary fibrosis and atypical epithelial proliferation (AEP) in a patient with multiple myeloma treated with melphalan is presented. Review of 10 other autopsied patients with myeloma treated with melphalan but no thoracic radiation, other cytotoxic agents, or highdose oxygen therapy revealed one other patient who died with extensive pulmonary fibrosis and AEP. Four other patients with AEP not associated with pneumonitis or fibrosis were also found, while no such changes were found in 11 autopsy controls or 11 patients with myeloma who did not receive cytotoxic agents. Melphalan should be added to the growing list of agents capable of causing severe fibrotic pulmonary reactions.


Calcium dependence of ionophore A23187-induced lymphocyte cytotoxicity.

Concentrations of the divalent cation ionophore, A23187, optimal for the transformation of human and pig lymphocytes, were cytotoxic to lymphocytes from rats and mice. The biochemical effects associated with A23187-induced cytolysis in rat thymocytes included inhibition of [3H]uridine uptake and incorporation into macromolecules and stimulation of [14C]-alpha-aminoisobutyric acid uptake. The biochemical effects, as well as the reduction in the number of viable cells, were dose dependent and were blocked by the omission of ionic calcium from the incubation medium. At a given ionophore concentration, the magnitude of lysis of thymocytes was proportional to the concentration of Ca2+ in the extracellular medium. Sr2+ was less effective than was Ca2+ in supporting A23187-induced thymocyte lysis. A comparison of the lytic response of lymphocytes of various origins showed that extracellular Ca2+ plays a role in ionophore-induced cytolysis in thymocytes and lymph node lymphocytes but not in mouse lymphosarcoma P1798 cells.


Heterogeneity in the membrane proteins of human lymphoid cell lines as seen in sodium dodecyl sulfate-polyacrylamide electrophoresis slab gels.

The proteins of [35S]methionine-labeled membranes of six human lymphoid cell lines were examined by electrophoresis in sodium dodecyl sulfate-polyacrylamide gradient slab gels in order to identify molecular differences among these tumors. The lymphoid cells were internally labeled with [35S]methionine, their membranes were isolated, and the reduced and alkylated membrane proteins were treated electrophoretically in sodium dodecyl sulfate-polyacrylamide gradient slab gels. The gel patterns of over 100 membrane proteins per cell were highly complex but reproducible and, in that sense, constituted fingerprints of the individual tumors. Several proteins occurred uniquely on one or a few tumors. Some protein bands were identified to be serologically recognized membrane antigens by electrophoresis of immunopurified antigen in parallel to membrane samples. p44,12, a complex of proteins with molecular weights of 44,000 and 12,000 (HLA-A and -B antigens and beta2-microglobulin), and p29,34, (HLA-D antigen) were identified in this manner. High-resolution sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis can be used to catalog and describe lymphocyte membrane proteins and perhaps to identify subsets of lymphoid cancers.


Vinyl carbamate as a promutagen and a more carcinogenic analog of ethyl carbamate.

Vinyl carbamate was much more active (10 to 50 times) than ethyl carbamate for the initiation of skin tumors and for the induction of lung adenomas in mice. Vinyl carbamate was also mutagenic to Salmonella typhimurium TA 1535 and TA 100 in the presence of reduced nicotinamide adenine dinucleotide phosphate-fortified rat or mouse liver mitochondrial supernatant fractions. This mutagenic activity was inhibited strongly by cytochrome P-450 inhibitors. No mutagenic activity was observed for vinyl carbamate in the absence of added liver preparations or for ethyl carbamate in the presence or absence of liver fractions. Extensive tests with sensitive methods failed to detect vinyl carbamate as a metabolite of ethyl carbamate in the mouse in vivo. However, on administration of [ethyl-1-14C;1,2-3H]ethyl carbamate to adult mice the 3H/14C ratios of the hepatic DNA-, rRNA-, and protein-adducts were similar to each other and much lower than the ratio of the administered ethyl carbamate. These data are consistent with the presence of desaturated and/or oxidized ethyl groups in the macromolecular adducts. The qualitatively similar, but much stronger, carcinogenic activity of vinyl carbamate as compared to that of ethyl carbamate suggests that the metabolic pathways of these two carbamates may converge in the formation of similar or identical electrophilic reactants that bind covalently to macromolecules in vivo and initiate carcinogenesis.


Population density as a factor in the evolution of neoplastic cell lines.

The influence of population density in the progression from the nonneoplastic to the neoplastic state has been reassessed. Two twice-cloned, nonneoplastic mouse lines, NCTC 7914 and 7915, were transferred each 3 to 4 days at inoculum sizes selected to minimize or maximize cell-cell contact, 1 X 10(5) or 4 X 10(5) cells/T-15, respectively. As tested by in vivo assay, the regime designed to minimize cell-cell contact did not reproducibly delay transformation, and tumor production was observed in all lines, irrespective of inoculum size. Also, results of tumorigenesis assays correlated with blind evaluation of morphological and cytological alterations, growth in agarose, and susceptibility to killing by activated macrophages. Generally higher saturation densities were seen as a function of period in culture, and no significant differences in glucose utilization or lactic acid production were observed between nonneoplastic and neoplastic cell populations.


Disposition and metabolism of 1-(tetrahydro-2-furanyl)-5-fluorouracil (ftorafur) in humans.

The pharmacology of high-dose 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) has been studied by radiochemical and chromatographic techniques in eight patients. Plasma disappearance of FT was exponential, with a half-life of 8.8 hr. Plasma concentrations of 5-fluorouracil (FUra) were sustained at 12.8 nmol/ml (1.7 microgram/ml) for at least 48 hr after FT administration. The concentrations of FUra derived from the administration of FT were considerably greater than were those achieved by constant infusion of FUra at the maximal tolerated dose of 1.1 g/sq m without causing unacceptable mucositis. The cumulative urinary excretion was 20% of the administered dose in 24 hr. FT underwent in vivo biotransformation to 2 hydroxytetrahydrofuranyl-5-fluorouracil derivatives in addition to anabolites and catabolites of FUra. High concentrations of FT and FUra were present in the cerebrospinal fluid, which could account for the severe central nervous system toxicity of FT at high doses. We conclude that the antitumor activity of FT is partially attributable to its slow release of FUra.


An overview of hormone-associated cancers.

Data on the etiology of hormone-associated cancers are reviewed. Although for breast cancer many risk factors point to the relevance of hormonal factors, findings are not uniform. Evidence points to the importance of dietary factors, and one study appears to confirm an association with high total fat intake. Dietary factors, although possibly mediated through a hormonal mechanism, may eventually be found to play a major role in the etiology of breast cancer. Studies of both endometrial and ovarian cancer also show the importance of hormonally associated factors, although not always in the same way as for breast cancer. In addition, both for these sites and for cancer of the prostate, dietary factors may also be relevant in their etiology. As yet, no direct assessment of the importance of diet has been attempted for these sites, but this could be rewarding.


Specificity of arrest, survival, and growth of selected metastatic variant cell lines.

Animal tumor models for blood-borne metastasis have been developed by in vitro cloning or in vivo selection of malignant tumor cell populations to obtain organ-preferring variant tumor cell lines with altered arrest, survival, invasion, and growth properties. Selection and some tumor cell characteristics of lung-, brain-, and ovary-colonizing metastatic B16 melanoma, liver-colonizing RAW114 lymphosarcoma, and lung-colonizing MSV3T3 vasoformative sarcoma variant lines will be discussed along with additional data, suggesting that tumor cells of varying malignant potential preeexist in the unselected tumor population.


Determination of cellular shape by the extracellular matrix and its correlation with the control of cellular growth.

Although the problem of cellular proliferation may seem at first glance to be tremendously complex, the mechanisms which control it may be extremely simple. One of the primary factors which regulates the mitogenic response of a given cell type to a given class of mitogenic agents seems to be the cellular shape. We have found that corneal epithelial cells, for example, adopt a flattened configuration when maintained in vitro on plastic and are very sensitive to fibroblast growth factor, but not to epidermal growth factor. When maintained on collagen, on the other hand, they become tall and columnar and respond primarily to epidermal growth factor. The cellular shape is dictated in vivo by the extracellular material upon which the cells rest and in vitro by the substrate upon which the cells are maintained. The substrate itself may, in turn, induce the cells to manufacture their extracellular material and specific cell surface proteins which control the cellular shape.


Unique steroid congeners for receptor studies.

To determine the hormone-dependence of a tumor, it is preferable to use highly specific radiolabeled ligands when available, since often more than one class of steroid hormone receptor is present in the tissue specimen, and interference from classes other than the one under study cannot be readily eliminated. In this study, we describe a simple in vitro system used to define the molecular requirements for a highly specific interaction between a steroid and the receptor corresponding to a single class of hormone. It is based on the use of homogenate or crude 105,000 X g supernatant prepared from the target organs considered as end points in routine biological potency tests and on the use of available radioligands not bound by plasma proteins (tags) to single out the receptors. For each receptor singled out in the target organ cytoplasm, the ability of over 700 molecules to decrease bound radioactivity was compared to that of the natural hormone (relative binding affinity) with the use of a dextran-coated charcoal technique to separate bound from unbound steroid. On the basis of the results on 81 molecules, presented in this study, the effect of various substituents on the affinity and specificity of the natural hormones was determined. Molecules interacting markedly with several receptors were submitted to X-ray crystallography in order to establish whether overlap between the various conformations of the natural hormone and of the test molecule might not partly account for lack of specificity.


Prognostic value of steroid receptor determination in leukemia.

Determinations of steroid receptors have been used to predict steroid sensitivity in various neoplastic tumors. It appears, however, that simple steroid binding measurements are not sufficient for that purpose in lymphoid tumors. This conclusion is based on a literature survey showing, first, that numerous factors are capable of modulating cellular steroid receptor content; second, that the results of steroid receptor determinations are critically dependent on experimental procedures; and, third, that the correlation between steroid receptor content and sensitivity is not obligatory in animal or human leukemic cells.


Steroid hormones and endometrial cancer.

The factors that increase the risk of development of endometrial cancer are reviewed. Many of these conditions are frequently associated with an elevated production of estrone in peripheral (nonendocrine) tissues from circulating androstenedione. Elevated estrone production may occur in young, anovulatory or postmenopausal women whose ovaries secrete higher than normal amounts of androstenedione. Alternatively, conditions such as obesity and liver disease are associated with higher than normal rates of conversion of androstenedione to estrone, resulting in high estrone levels. Neither the exact tissue site(s) of conversion nor the normal function of this process has yet been established. Much less information concerning steroid hormone receptor measurements in endometrial cancer than in breast cancer is available. However, it seems certain that measurement of progesterone receptors will provide a useful guide in the selection of progestational therapy.


Studies on some biologically active dextrans.

The relationship between the structures of six native dextrans and their effects on nonspecific resistance to infection (n.s.r.i.) in mice and also anticomplementary activity has been studied. The data obtained showed that the n.s.r.i. activity of dextrans generally increased with increase of extent of branching, but no direct correlation between these two factors was found. Data on exodextranase-catalyzed hydrolysis of dextrans suggest that the length of the outer chains may be important for the n.s.r.i. activity of the dextrans. Dextrans characterized by a significant extent of branching were anticomplementary, but no relationship between extent of branching and anticomplementary activity was observed.


The National Exercise and Heart Disease Project. The pre-randomization exercise program. Report number 2.

The National Exercise and Heart Disease Project (NEHDP) was funded by the Rehabilitation Services Administration (RSA) of the Department of Health, Education and Welfare, to determine the effects of regular physical activity on the rehabilitation, morbidity and mortality of patients with healed myocardial infarctions. Planning and development lasted from June 1972 through September 1974. Since 1974, 932 subjects were referred for evaluation. At randomization, 651 subjects were assigned to exercise treatment (323) or control (328) groups. Those who qualified for randomization had to complete an initial evaluation, attend 14 of 18 consecutively scheduled, low-level physical activity sessions during a period of 6 weeks, and complete a second evaluation. This prerandomization phase was accompanied by significant alterations in work capacity, heart rate levels at rest and during three levels of physical stress, systolic blood pressure reductions during stress but not at rest, and by changes in the level of anxiety and depression. The subjects will be followed for a minimum of 2 years at regular intervals to determine if regularly performed physical activity is beneficial to the rehabilitation of myocardial infarction survivors.


Pitfalls in the diagnosis of pericardial effusion.

Echocardiography has proven to be a sensitive and reliable technique in the diagnosis of pericardial effusion. Care must be taken in recording to maintain proper angulation of the transducer, to scan adequate sites, and to maintain proper gain settings. The following entities may mimic pericardial effusion and must be excluded by careful analysis: left pleural effusion, mitral annulus calcification, anterior mediastinal space-occupying lesions, fibrinous pericardial reactions, and right heart catheters. Care must also be taken in the quantitation of pericardial fluid and in hemodynamic extrapolation.


Clinical applications of real-time two-dimensional scanning in congenital heart disease.

Real-time two-dimensional visualization of cardiac anatomy has been a major advance in the noninvasive evaluation of congenital heart disease. Performed from precordial or suprasternal notch sites, the techniques allow noninvasive evaluation of the cardiac chambers, atrioventricular valves, and great arteries for the diagnosis of common and complex forms of congenital heart disease. Two-dimensional real-time echocardiography, therefore, can be expected to become an integral part of the noninvasive diagnosis and serial followup of children and infants with congenital heart disease.


Echocardiography in current perspective.

Expensive cross-section echocardiographic recorders have been introduced only recently in a small number of medical centers in this country. More information is needed to determine the sensitivity and specificity of this technique for the diagnosis of various cardiac abnormalities. In contrast, M-mode echocardiography is an accepted and routine laboratory procedure. However, the clinician should be aware of the problems of technique and interpretation so that information obtained can be correctly utilized in relation to the clinical setting. The physician should assume a flexible attitude in this expanding field, and rigid dogmatic criteria should be avoided. Only in this way will echocardiography develop and be used to fullest advantage in clinical medicine.


The functional and structural border of the neurohemal region of the median eminence.

In stressed rats the tanycytes of the ventrolateral wall of the third ventricle exhibit by light microscopic immunohistochemistry a positive staining for neurohormones which is distinctly limited to the distal perivascular end of the tanycyte process. Since by electron microscopic immuncytochemistry the tanycyte cytoplasm does not show any reaction product, the light microscopic reaction most likely results from a labeling of the intercellular space in the direct vicinity of the subendothelial cleft. Whether this subendothelial space is permeable to neurohormones was tested by injection of HRP1. In the region of the arcuate nucleus 30 min after intravenous application, the marker is affixed to the membranes of the perivascular tanycyte processes in the subendothelial cleft of capillaries possessing non-fenestrated endothelia. Occasionally, HRP penetrates for a short distance between the tanycytes. Then the labeling of the intercellular cleft ends abruptly. Here, several parallel ridges of tight junctions between the perivascular distal tanycyte processes are found by the freeze-etching technique. Since HRP cannot reach the subendothelial clefts of this region by passing through capillary walls due to the presence of a blood-brain barrier, it is suggested that the marker penetrates from the median eminence this far via the subendothelial extracellular space. It is prevented from spreading further by the tight junctions of the perivascular tanycyte endings. The same way may be taken by the neurohormones. Hence, a border area exists adjacent to the dorsolateral aspect of the neurohemal region of the median eminence where the tanycytes isolate the neuropil from the cerebrospinal fluid not only by their apical tight junctions, but also by basal tight junctions from the subendothelial cleft. This communicates with the perivascular space of the portal vessels.


Paddle cilia and discocilia - genuine structures? Observations on cilia of sensory cells in marine turbellaria.

Kinocilia of epidermal sensory cells in fixed marine Turbellaria often terminate as flattened biconcave discs. The distal part of the ciliary axoneme curves back upon itself forming a 360 degree loop which is enveloped by the plasmalemma. In living animals this structure can be induced by the addition of sodium cacodylate, monobasic sodium phosphate, dibasic sodium phosphate, sucrose, calcium chloride, or formaldehyde to the sea water. Specimens treated with sodium chloride, glutaraldehyde, or osmium tetroxide do not show modified cilia. In animals prepared for EM at low temperature and with a buffered hypotonic fixative less kinocilia are modified than in animals treated with a buffered iso- or hypertonic fixative and at a higher temperature. It is assumed that the unusually shaped cilia, described as "paddle cilia" or "discocilia" in other invertebrates, do not represent a genuine but an artificial structure.


Gastrin and the ultrastructure of G cells after stimulation with acetylcholine.

The effect of intragastric administration of acetylcholine on serum and antral gastrin concentrations of rats has been examined using a radioimmunoassay and quantitative electron microscopy. Exposure of the stomach of rats, previously fasted for 24h, to 2% acetylcholine for either 0.5 or 2h resulted in a significant 4--5 fold increase in serum gastrin concentrations to levels similar to those found in fed animals. Such treatment produced no detectable change in antral gastrin concentration or in the number or electron density of secretory granules in the G cells. This lack of detectable change in the G cells was not unexpected since our calculations suggest that less than 10% of the total gastrin stored in the antrum is released over 2h as a result of the stimulation with acetylcholine. The proportion of electron-lucent secretory granules was, however, markedly increased by prolonged fixation in aldehydes. The increase was similar in both ACh stimulated and control animals. These results indicate that the ultrastructural appearance of G cell secretory granules in influenced far more by the conditions of fixation than by the release of gastrin. They therefore cast considerable doubt on the hypothesis that gastrin is released by molecular dispersion from the granules.