Effects of chronic hypoxia and dietary restriction on myocardial enzyme activities.

Enzyme activities were measured in homogenates of left and right ventricles of guinea pigs after 14 and 28 days' exposure to 400 mmHg barometric pressure. All animals developed anorexia and right ventricular hypertrophy. Two control groups of animals were used, one free fed and the other restricted to the amount of food chosen by the hypobaric group. The factorial design of the experiment allowed some distinction between the effects of anorexia, hypertrophy, and hypoxia. Dietary restriction was associated with a decrease in glycogen phosphorylase, hexokinase, and succinate dehydrogenase activity and an increase in the M-subunits of lactate dehydrogenase. Myocardial hypertrophy was associated with an increase in the activity of the enzymes of the glycolytic pathway down as far as phosphoglycerate kinase and an increase in the M-subunits of lactate dehydrogenase. Chronic hypoxia seemed specifically to be associated with an increase in the H-subunits of lactate dehydrogenase and possibly a slight transient increase in succinate dehydrogenase activity. Mixing studies indicated that changes in enzyme activities were likely to be due to changes in enzyme concentrations.


Providing for the severely handicapped: a case for competency-based preparation of occupational therapists.

Recent court decisions that mandate the development of new instructional alternatives for severely handicapped children will have significant implications for occupational therapists. Focusing on such issues as mainstreaming, accountability, and certification standards, this paper places in perspective the problems and trends that have led to this new challenge. It also provides suggestions for the development and disposition of training programs that can ultimately result in more appropriate programming for the handicapped children in the new population to be served in the public schools. Illustrated with examples of competency components and behavioral objectives, competency-based occupational therapy preparation programs are emphasized.


Potassium secretion by colonic mucosal cells after potassium adaptation.

Recent studies have demonstrated that chronic potassium loading increases Na-K-ATPase specific activity in kidney tissue and suggest that this enzyme plays a role in renal potassium adaptation. Studies of fluid and electrolyte movement, potential difference (PD), AND Na-K-ATPase were performed in colon and jejunum of the rat in order to further characterize the relationship of Na-K-ATPase to potassium secretion. Experimental rats fed 2.6 meq K/gm diet for 7 days were compared to a control group fed 0.13 meq K/gm. In the colon, chronic potassium loading increased potassium secretion from 0.8 +/- 0.2 to 3.9 +/- 0.9 mueq/min per g tissue (P less than 0.01) and PD from 27 +/- 5.0 to 54 +/- 2.6 mV (P less than 0.001), lumen negative, as Na-K-ATPase increased from 5.0 +/- 0.5 to 11.4 +/- 1.0 muM Pi/mg protein per h (P less than 0.001). In contrast, there was no change in PD, potassium movement, or Na-K-ATPase in the jejunum of potassium-loaded rats. Colonic movement of water, sodium, and chloride was similar in the control and potassium-loaded rats. These results indicate that increased Na-K-ATPase is associated with both increased PD and increased potassium secretion in the colon and provide additional evidence suggesting that Na-K-ATPase may be important in the control of transepithelial potassium movement.


Saturation kinetics of sodium efflux across isolated frog skin.

Measurement of Na efflux across the frog skin epithelium from the serosal side to the outside (JNa 3 leads to 1) in a new chamber specifically designed to avoid edge damage shows that JNa 3 leads to 1 exhibits saturation kinetics with a maximal efflux (Jmax) of 31.8 nmol/cm2 per h and an apparent KNa of 4.0 mM. In contrast, JNa 3 leads to 1 measured in conventional chambers and efflux determinations in the new chamber of substances that pass the epithelium via extracellular pathways (polyethylene glycol 900, sucrose, mannitol) exhibit a linear relationship between the efflux of the substance in question and its concentration in the bath. In addition, changes in external Na concentration do not cause substantial changes in JNa 3 leads to 1. The saturation remains but both Jmax and KNa increase after application of ouabain. Amiloride, as well as dinitrophenol, eliminates the saturation and JNa 3 leads to 1 becomes a linear function of Na concentration. The separate effects of ouabain and amiloride suggest that these two inhibitors  which are known to affect two distinctly different steps in the active transport pathway act also on two separate steps of JNa 3 leads to 1: the passage across the inward- (serosal) and outward-facing (apical) cell membranes of the epithelial cells, respectively. The action of dinitrophenol indicates the involvement of metabolism in JNa 3 leads to 1 probably at the latter of the two steps. The results suggest strongly that JNa 3 leads to 1 proceeds not via a paracellular but via a transcellular pathway that interacts with the active transport pathway.


Reporting of Down's syndrome from birth certificate data in the State of Minnesota.

Following a study of 421 suspected cases of Down's syndrome which were referred during a 10-year period to the Human Genetics Unit of the Minnesota Department of Health for chromosomal analysis, the following conclusions were reached: 1. There was an overall underreporting on the matched birth certificate of 52% of the cytogenetically confirmed cases. 2. This underreporting on birth certificates was greater (79%) for those born in the years 1946-1964 when less specific information was requested than in more recent years (36%), 1967-1974, when identification of the abnormality was requested.


Renal artery false aneurysm. An unusual complication of prosthetic patch angioplasty.

False aneurysm formation in a twenty-nine year old black woman treated for renovascular hypertension secondary to fibromuscular hyperplasia by knitted Dacron prosthetic patch angioplasty is reported. Etiologic mechanisms are discussed. The most likely factors leading to false aneurysm formation in this patient are disproportionate compliance between the arterial wall and the prosthesis and increased rigidity of the prosthesis, associated with increased shearing and vibratory stress. This patient was treated successfully by resection of the prosthetic path and involved artery with end-to-end reanastomosis of the artery.


Cryoultramicroscopy of the retina and choroid in rat.

Preparations of ultrathin frozen sections of the retina and choroid in rat were studied by the new technique of Tokuyasu (1973). All membrane structures were observable in ultrathin frozen sections, so that this method is likely to be most valuable for the morphologic study of membranes. However, there are some disadvantages to the use of this technique in that identification of some intracellular organelles such as ribosomes and glycogen is difficult. A fibrous dense network was observed in the interphotoreceptor spaces, the intermicrovilli spaces of the pigment epithelium, and it appeared in the space between the photoreceptor and the microvilli. The network almost disappeared after treatment with hyaluronidase for 30 min, suggesting that it may consist of aid mucopolysaccharide.


[The influence of cortisol treatment on the development of diabetic cataracts in rats (author's transl)].

The influence of daily subcutaneous cortisol injections (10 mg/kg) on the development of cataracts in streptozotocine (STR) diabetes was studied in 6 groups of Wistar rats (n = 10). Cataracts occurred only in the two groups subjected to high STR doses (60 mg/kg). We were astonished to find that in cortisol-treated diabetic animals there were lower blood glucose levels, fewer cases of glucosuria, and less pronounced cataracts than in rats treated with STR only. As STR had been administered after the start of cortisol therapy, it is assumed that the steroid had caused a protection of pancreatic B cells against STR and the onset of a less severe diabetes.


The bulbourethral gland of the rat. Fine structure and histochemistry.

The bulbourethral gland of the rat was studied, using ordinary light microscopy, electron microscopy and histochemistry. It is a lobular gland and, centrally in each lobe, there is a duct, the ampulla, into which the alveoli drain, either directly or via a very short and narrow ductule. In some glands all the alveoli are cyst-like dilated. The alveoli and ampullae are bounded by tall glandular cells with flattened basal nuclei. The cytoplasm is full of secretion granules. There is only one large secretory duct into which all the ampullae open and this leave the gland at one end. In the electron microscope the granules can be seen to be surrounded by a unit membrane, but quite often several granules flow together in a large irregular mess. Some granules have dense corn-like structure, while others are quite light. A non-membrane bounded mass can often be seen in the luminal part of the cells, this projects as a dome in the alveolar lumen. Myoepithelial cells can be seen around the secretory cells. The histochemical investigation showed that the gland cells are in between mucous and seromucous cells. In the main they contain acid mucosubstances, but also some neutral mucosubstances. The acid mucosubstances consist mainly of sulfated acid mucosubstances and a smaller amount of carboxylated acid mucosubstances (sialomucin).


The fine structure of the outer capsule of the snout muscle spindle in the Japanese lesser shrew-mole.

The fine structure of the outer capsule of the snout muscle spindles of the Japanese lesser shrew-mole (42 spindles from 9 animals) was described electron microscopically. The capsule of the snout muscle spindle is composed of 5 to 6 layers of the so-called capsule cells derived from the perineural epithelium of the peripheral nerve which supplies the spindle. The capsule cells revealed the presence of numerous pinocytotic vesicles, granular endoplasmic reticulum, abundant ribosomes, mitochondria, dense bodies, microvesicles and Golgi complex. It would be highly suggestive of their secretory or transporting activity. The various types of plication within the capsule of the muscle spindle were detected in the equatorial region. By means of such projections the functioning surface of the outer capsule has been enormously increased.


The mucopolysaccharide pattern in the retina after laser treatment.

Albino mouse retinas were irradiated with a ruby pulse laser. After irradiation, an increase in acid mucopolysaccharide was observed in the interreceptor matrix.


Influence of medication on development of serum antibody to swine dysentery as detected with indirect fluorescent antibody method.

Serums from 119 swine exposed to swine dysentery inoculum, and medicated with various drugs, were tested for antibodies to the large spirochete, using the indirect fluorescent antibody test, and were compared in tests with known positive serums from 18 nonmedicated swine which had recovered naturally. An inverse relationship existed between the efficacy of the drug and the serum antibody titer (highest dilution of the serum producing immunofluorescence of large spirochetes). The more efficacious drugs or doses resulted in lesser development of serum antibody. Diarrhea usually seemed necessary for the development of serum antibody. With the less efficacious drugs, there were more days of diarrhea. Some swine had diarrhea but did not develop an antibody titer, and a few swine had a titer but did not develop diarrhea. Swine which developed a titer were more immune against reexposure with infective inoculum. The medicaments, especially those given at higher concentrations, seemed to resolve the diarrhea or prevent the development of diarrhea, occurrences which were necessary for the development of immunity.


In vitro susceptibility and resistance of animal staphylococci to macrolide antibiotics and related compounds.

Strains of Staphylococcus aureus isolated from poultry, pigs and cases of bovine mastitis and strains of S. hyicus isolated from pigs were examined for their susceptibility of the macrolides and other related antibiotics. The susceptibility of these strains to erythromycin, oleandomycin, tylosin, spiramycin, lincomycin, clindamycin, virginiamycin, and its components virginiamycin S and M, was tested by the quantitative plate dilution method. With S. aureus, 3 p. 100 of the bovine, 12 p. 100 of the avian and 53 p. 100 of porcine isolated were found to be resistant. With S. hyicus strains 76 p. 100 were found to be resistant. Most resistant strains showed the generalized constitutive macrolide-resistance type. Twelve p. 100 of the porcine S. aureus strains were resistant to the virginiamycin component M.


Detection of aneuploid cells in fibroblast cultures from the father of two trisomy 21 patients.

Karyotype analysis was performed on successive cultures of fibroblasts from the parents of two trisomic 21 patients. Starting from the 7th passage in the father cultures an aneuploid clone showing an extra E-like chromosome was found, which eventually overgrew the cell population. The significance of this cytogenetic finding is discussed in relation to the recurrence of the trisomy in the family.


[Partial trisomy of chromosome 21 by maternal translocation t(15;21) (q26.2; q21)].

A balanced reciprocal translocation, t(15;21) (q262;q21) was observed in the mother and maternal grandfather of two patients. The propositus, who received the abnormal chromosome 15 from his mother, is trisomic for the distal part of chromosome 21, and his phenotype is that of classical trisomy 21. His sister, who is trisomic for the proximal part of 21q, is slightly retarded but developmentally normal otherwise.


Safety of long-term tetracycline therapy for acne.

Results of blood chemistry studies using an automated multiple analysis system and blood cell counts for 325 patients receiving long-term low-dosage tetracycline hydrochloride therapy continuously for three years or longer revealed minimal changes in all but one patient. This patient developed a transient hyperbilirubinemia with mild juandice while taking 500 mg of tetracycline daily.


Role of suppressor cells in antibody-induced inhibition of mixed lymphocyte reactions.

Facilitating immune sera (FIS) have both in vivo enhancing and in vitro blocking properties. They inhibit the mixed lymphocyte reaction (MLR) in the mouse. In the present report, we studied the inhibitory capacity of these sera after removal of populations of suppressor cells both in vivo by adult thymectomy and in vitro by depletion of histamine-receptor-bearing cells (HRC). A significant decrease of the MLR inhibition by FIS after either of these depletions was observed. It appeared therfore that facilitating antibodies and thymus-dependant and/or HRC could cooperate in the antibody-induced inhibition of the MLR in the mouse.


Effect of lithium on brain 5-hydroxytryptamine metabolism in mice.

Administration of lithium carbonate (2 mEq/kg) i.p., twice daily for 3 days to mice did not significantly after brain 5-hydroxytryptamine (5-HT) levels; however, brain 5-hydroxyindoleacetic acid (5-H1AA) accumulation after i.p. injection of probenecid (200 mg/kg) was significantly increased in lithium pretreated animals. Brain 5-hydroxytryptophan decarboxylase activity was enhanced by lithium pretreatment while brain monoamine oxidase (MAO) activity was unaltered. After i.p. injection of the monoamine oxidase inhibitor pargyline (100 mg/kg) the accumulation of brain 5-HT was greater in lithium treated than control mice, while the decrease in brain 5-HT levels after i.p. treatment with the 5-HT synthesis inhibitor para-chlorophenylalanine (PCPA 300 mg/kg) was significantly less in lithium pretreated mice.


Effects of para-chlorophenylalanine and tryptophan on learning of a brightness discrimination in rats.

Both the learning of brightness discrimination, discrimination reversal and a simple oddity problem, and the pain-sensitivity to electric shock were studied in rats treated with 100 mg/kg of D, L-parachlorophenylalanine (PCPA), 100 mg/kg of D, L-tryptophan (TP) or 2.0 ml/kg of control solution (CS). At the end of the last behavioral session all animals were killed and the levels and rate of 5-hydroxytryptamine (5-HT) synthesis were measured. PCPA treatments produce rats which are more effective in coping with a problem; these animals were similar in that both the levels and turnover rate of brain 5-HT and the pain-sensitivity were lower. Results are tentatively explained suggesting that these differences in learning ability could be a result of the drug's action in pain-sensitivity. The possibility that 5-HT might be responsible for these differences is discussed.


A reduced pyridine nucleotides-diaphorase activity associated to the assimilatory nitrite reductase complex from Neurospora crassa.

The Neurospora crassa assimilatory NAD(P)H-nitrite reductase complex has associated a NAD(P)H-diaphorase activity. 1. This NAD(P)H-diaphorase activity can use either mammalian cytochrome c, 2,6--dichlorophenol-indophenol, ferricyanide, or menadione as electron acceptor from the reduced pyridine nucleotides, and requires flavin adenine dinucleotide for maximal activity. 2. It is inhibited by p-hydroxymercuribenzoate, 1 muM, and it is unaffected by cyanide, sulfite, or arsenite at concentrations which completely inhibit the NAD(P)H-nitrite reductase activity. 3. Flavin adenine dinucleotide specifically protects the NAD(P)H-diaphorase activities, but not the NAD(P)H-nitrite reductase activities, against thermal inactivation. 4. In vitro preincubation of the Neurospora crassa nitrite reductase complex with reduced pyridine nucleotides plus flavin adenine dinucleotide inactivates the NAD(P)H-nitrite reductase activities, but does not affect the NAD(P)H-diaphorase activities, indicating that this nitrite reductase inactivation occurs in the part of the enzyme that contain the nitrite reducing center.


Human left ventricular ultrastructure. Clinical and laboratory catheterization correlation.

Biopsy specimens of the myocardium for electron microscopical study were taken from patients who were having surgical operations for correction of aortic and mitral valve lesions. Ultranstructural changes characteristic of hypertrophy and ischemia were found in the left ventricles of groups with aortic and mitral lesions. The severity of the cardiomyopathy was greater in hearts that had aortic lesions than in those that had mitral lesions. Both groups, however, displayed degenerative changes to an extent not readily appreciated or expected when their clinical histories and catheterization data were obtained.


Arm veins for peripheral arterial reconstruction.

The ipsilateral saphenous vein has become accepted as the best available material for femoropopliteal bypass and for arterial patch grafts as well as for visceral and cardiac bypasses. However, in a few patients, nonavailability or nonsuitability of the saphenous vein forces use of some other material. We report an experience with 32 operations using arm veins. Among the 11 long vein grafts, seven composite vein-Dacron or vein-vein grafts, and 14 vein patch grafts during the past six years, there were no infections or aneurysms and only nine thrombotic failures have been detected to date, to our knowledge. Our present indications are (1) ipsilateral saphenous vein is not available or is not suitable, (2) only a short graft or patch is needed and the saphenous vein may therefore be saved for the future, (3) to join to a saphenous graft or to a Dacron composite graft for additional length, and (4) to reconstruct an arm artery. Our experiences using cephalic and basilic veins confirms them as a useful source of autogenous material for arterial reconstruction.


[Neuromuscular spindles of several amphibia and reptiles].

The work presents data on the structure and innervation of the nerve-muscle spindles in the soleus of the lake from Rana ridibunda, Bufo bufo, turtle Testudo horsfieldi, lizzard Lacerta agilis. The animals under study were shown to have different structure and innervation of these receptors. The thickness of the spindle connective tissue capsule has certain correlation with the width of the subcapsular space. The innervation apparatus in the muscle spindles of reptiles and turtles are similar in the following: sensory nerve terminations in the equatorial area of the spindle are represented by reticulars, bushes, loops and in the lizzard there appear annulo-spirals with a small amount of coils. The character of motor nerve terminations  in polar zones of intrafusal muscle fibres in the spindles of reptiles is similar to that of the extrafusal fibres: in the shape of "bayonets" and end bundles (Endbüuschel). In the muscle fibres of the turtle and lizzard in addition to typical motor plaques there occur trail endings.


Some effects of pressure treatment on actomyosin systems.

Natural actomyosin, actin and myosin, have been pressurized at up to 150 MN/m2 for 1 h at 0 degrees C and examined 3-5 h later. Pressurization of myosin resulted in the formation of aggregates with a molecular weight approximately that expected for a dimer, whereas with F-actin depolymerization occurred. With actomyosin, a gel to sol transition was promoted. Viscosity and light-scattering measurements indicated that pressurization results in a large measure of disaggregation of actomyosin in solution. Pressurization of actomyosin resulted in a greater decrease in the calcium-sensitive, than in the calcium-independent, Mg2+ ATPase activity. The Ca2+ and K+-EDTA ATPase activities of myosin were inhibited to about the same extent.


Effects of methylcholanthrene on epidermal growth regulators. II. Variations in the S-factor.

There is increasing evidence to support the existence of tissue-specific growth-inhibitory chemical substances which can be found in extract homogenized cells. In the epidermis, two such tissue-specific factors (which also have cell-cycle specificity) have been found. These factors act specifically on different phases of the cell cycle (epidermal G1 and G2 chalones, respectively). This paper concerns a study of the effect of 20-methylcholanthrene on the epidermal G1 chalone. The variations in epidermal G2 inhibitor after such treatment were described in a previous paper. Hairless mice received a single topical application of 0.2 ml 0.5% solution of the carcinogen. The short time effect of the carcinogen application on epidermal DNA synthesis was first studied. Other groups of carcinogen-treated mice were then killed at similar time intervals, and the treated area of skin was homogenized and extracted with water. The inhibitory effect of these extracts on normal epidermal G1 cells was assayed in normal hairless mice. The obtained inhibition was registered as an expression of G1 inhibitor concentration in the skin extracts. The first experiment confirmed that a single carcinogen application provokes a short block in epidermal DNA synthesis, followed by a high, biomodal peak of increased activity with the first and maximum peak on day 2, and a smaller peak on day 8 after treatment. The second experiment showed that the content of G1 chalone in the skins of treated animals varied inversely to the alterations in epidermal DNA synthesis, revealing almost no chalone activity on day 2, and reduced chalone activity on day 8.


DNA and the cell cycle.

The cell cycle and its significance for pathology is reviewed. The molecular basis and questions of regulation in the cell cycle are discussed, along with deviations from the normal cycle in the form of polyploidy formation and aneuploidy in tumor cells. Automated prescreening processes may play a role in the future in daily routine diagnosis. Methods of cytophotometry with the possibility for objective pattern recognition will become significant in pathology in many ways, both in research and in routine work.


[Occupational dermatoses due to polyurethane drugs].

Twenty cases of occupational dermatoses caused by isocyanates, especially diphenylmethane diisocyanate (MDI), isophorone diisocyanate (IPDI), toluene diisocyanate (TDI) and tri-isocyanate-triphenylmethane are reported. The handling of patch test substances is described. Personal in test laboratories have to be considered as persons at risk. Findings give some evidence for cross-sensitization between MDI and the corresponding diamine diaminodiphenylmethane. Moreover, it is supposed that MDI may give rise to cross-sensitization to p-phenylene diamine and chemically related compounds.


[Occupational dermatoses of workers in a detergent factory].

133 female and 34 male workers of a detergents factory were subdivided into 3 groups according to the pathological state of their skin. The 129 persons of the first group showed slight disorders of the skin of their hands and forearms, the 31 subjects in the second group were free from skin disorders while the 7 persons of the third group showed eczematous symptoms. Patch tests were performed in these subjects using the following allergens: potassium dichromate, nickel sulfate, cobaltous chloride, formaline and paraphenylenediamine. Moreover, patch tests and wetting tests were carried out using the detergent powder manufactured in the factory. The results were mostly negative. In 66 cases of skin disorders, functional tests were performed that revealed disturbances of the barrier function of the skin (diminution of the alkali resistance by 62.2%, prolongation of the neutralization time by 75.6%, increase of the permeability by 33.2%). In 81.5% of the workers, a dermatosis due to overstrain was diagnosed.


3-oxo acid coenzyme A-transferase in normal and diabetic rat muscle.

The amounts of succinyl-CoA--3-oxo acid CoA-transferase (EC 2.8.3.5) decrease progressively in skeletal muscle in streptozotocin-diabetic rats, reaching after 10 days about 50% of the value in normal rat muscle. Electrofocusing studies indicate the occurrence of partial proteolysis of the enzyme in diabetic muscle. However, several functional parameters relating to acetoacetate utilization, including substrate inhibition, are quite similar for muscle transferase preparations from normal and diseased rats. The development of pathological ketoacidosis is discussed in the light of these observations.


Glucose metabolism in perfused skeletal muscle. Effects of starvation, diabetes, fatty acids, acetoacetate, insulin and exercise on glucose uptake and disposition.

1. The regulation of glucose uptake and disposition in skeletal muscle was studied in the isolated perfused rat hindquarter. 2. Insulin and exercise, induced by sciatic-nerve stimulation, enhanced glucose uptake about tenfold in fed and starved rats, but were without effect in rats with diabetic ketoacidosis. 3. At rest, the oxidation of lactate (0.44 mumol/min per 30 g muscle in fed rats) was decreased by 75% in both starved and diabetic rats, whereas the release of alanine and lactate (0.41 and 1.35 mumol/min per 30 g respectively in the fed state) was increased. Glycolysis, defined as the sum of lactate+alanine release and lactate oxidation, was not decreased in either starvation or diabetes. 4. In all groups, exercise tripled O2 consumption (from approximately 8 to approximately 25 mumol/min per 30 g of muscle) and increased the release and oxidation of lactate five- to ten-fold. The differences in lactate release between fed, starved and diabetic rats observed at rest were no longer apparent; however, lactate oxidation was still several times greater in the fed group. 5. Perfusion of the hindquarter of a fed rat with palmitate, octanoate or acetoacetate did not alter glucose uptake or lactate release in either resting or exercising muslce; however, lactate oxidation was significantly inhibited by acetoacetate, which also increased the intracellular concentration of acetyl-CoA. 6. The data suggest that neither that neither glycolysis nor the capacity for glucose transport are inhbitied in the perfused hindquarter during starvation or perfusion with fatty acids or ketone bodies. On the other hand, lactate oxidation is inhibited, suggesting diminished activity of pyruvate dehydrogenase. 7. Differences in the regulation of glucose metabolism in heart and skeletal muscle and the role of the glucose/fatty acid cycle in each tissue are discussed.


Kinetics of salicylate metabolism.

1 Nine patients with rheumatoid arthritis or non-inflammatory backache were given soluble aspirin (65 mg/kg body weight) daily. There was no significant difference between the plasma salicylate of those with rheumatoid arthritis and those with backache. 2 Two patients had plasma salicylate values that differed significantly from the remainder but neither these results nor the marginal differences between plasma salicylate levels of the others could be explained by individual variations in the capacity for excreting salicyluric acid or salicyl phenolic glucuronide. 3 Increasing the dose of aspirin in four patients demonstrated the reduced proportions of salicyluric acid and salicyl phenolic glucuronide excreted at high doses and the increased importance of unchanged salicylic acid as an excretory pathway. These findings are consistent with a limiting capacity for salicyluric acid and salicyl phenolic glucuronide synthesis and excretion. 4 The findings in one patient suggested that inter-subject variations in the capacity for producing salicyl phenolic glucuronide and salicyluric acid may have an effect on plasma salicylate levels at high doses of aspirin.


Tuberculosis after corticosteroid therapy.

Fourteen episodes of reactivation of tuberculosis after corticosteroid administration are reported. In most a disease impairing the host defences was present and four were taking additional immunosuppressants. The most common presenting symptoms were productive cough and malaise. Bacteriological diagnosis required bronchoscopy in three cases. Response to antituberculosis therapy was good. Five of the 14 episodes manifested dissemination of pulmonary tuberculosis with four occurring in patients receiving high-dose corticosteroids and other immunosuppressants. No prolongation of sputum conversion time was noted in the patients. The published effects of corticosteroids on the tuberculous state are reviewed. Because INH administration may cause liver damage in a small minority of patients, a reassessment is required of the need for INH chemoprophylaxis when corticosteroids are used in patients with healed tuberculosis.


Macrophage inhibitor factor (MIF) in cutaneous lymphoproliferative diseases.

Macrophage migration inhibitor factor (MIF) activity in the sera of patients with mycosis fungoides, Sézary syndrome, and cutaneous lymphoma was observed in the sera of eight of the ten patients with stage II (infiltrative) mycosis fungoides, but in only one of the eight patients with stage I and in neither of the two patients with stage III mycosis fungoides. Two of the three patients with Sézary syndrome had MIF in the serum. No MIF was observed in cutaneous lymphoma. These data support the concept that Sézary syndrome and mycosis fungoides are T-cell diseases, and transitional, prelymphomatous diseases.


Plasma volume, intravascular albumin and its transcapillary escape rate in patients with extensive skin disease.

Plasma volume and plasma concentration and transcapillary escape rate of albumin (TER alb), i.e. the fraction of intravascular mass of albumin that passes to the extravascular space per unit time, were determined using 125I-labelled human albumin in eight patients with extensive skin disease. Plasma volume and plasma albumin concentration were reduced (P less than 0-05). Thus the intravascular albumin mass was moderately decreased to an average of 0-55 +/- 0-06 (s.d.) g/cm height compared with a normal mean value of 0-77 +/- 0-07 (s.d.) g/cm. This 29% decrease is statistically significant (P less than 0-001). The transcapillary escape rate of albumin (TER alb) was significantly elevated, mean 8-6 +/- 1-1 (s.d.) % X h-1, as compared to normal subjects, mean 5-6 +/- 1-1 (s.d.) % X h-1, (+54%, P less than 0-001). The same patients were studied again after a 1-week treatment with prednisone, 25-60 mg per day. Plasma albumin concentration, plasma volume and intravascular mass of albumin were unchanged, while TER alb decreased significantly during treatment, mean 5-9 +/- 0-8 (s.d.) % X h-1, (P less than 0-01). It is suggested that displacement of albumin into the skin and loss of albumin from the skin are the dominating mechanisms of the reduction in the intravascular albumin mass in patients with extensive skin disease.


Studies on calcium transport and calcium-dependent adenosine triphosphatase activity of erythrocyte membranes in hereditary spherocytosis.

Evidence has been recently presented of a relative deficiency of Ca2+ - dependent adenosine triphosphatase activity of erythrocyte membranes obtained from patients with hereditary spherocytosis. We have sought to confirm these findings by measuring calcium efflux from intact erythrocytes of patients with hereditary spherocytosis, as well as erythrocyte calcium concentrations, but find both these parameters to be normal. Ca2+-dependent adenosine triphosphatase activity, as well as Ca2+ -dependent membrane phosphorylation was also not found to be deficient in erythrocyte membranes from subjects with hereditary spherocytosis. These studies do not support the postulate that an accumulation of calcium affects the deformability of erythrocytes and their subsequent destruction in the spleen.


Laparoscopic sterilization with an elasticated silicone ring.

A method of laparoscopic sterilization using an elasticated silicone ring is described. It was used in 155 patients over a period of 13 months by 12 gynaecologists. There were 12 complications specifically related to the method and only one of them required laparotomy. One tubal patency was discovered, but no pregnancy occurred in a total follow-up period of 81-25 years. Many patients had pain in the first 24 hours after operation but only 3 per cent had pain after three months.


Inhibition of (Na+, K+)adenosine triphosphatase and its partial reactions by quercetin.

The bioflavonoid, quercetin, inhibited the (Na+, K+)adenosine triphosphatase purified from the electric organ of electric eel (Electrophorus electricus) or from lamb kidney. An analysis of its mode of action revealed that the formation of phosphoenzyme from Pi but not from ATP was inhibited. Quercetin increased the amount of ADP-sensitive phosphoenzyme (E1--P), indicating an inhibition of the conversion of E1--P to the ADP-insensitive form (E2--P). The rate of dephosphorylation of the phosphoenzyme formed from ATP was slowed by quercetin. These results suggest that quercetin inhibits the formation of E2--P from either Pi or E1-P as well as the hydrolysis of the phosphoenzyme. Its mode of action is therefore different from that of ouabain and other inhibitors of the Na+, K+)adenosine triphosphatase.


Calorimetric studies of the interaction of magnesium and phosphate with Na+, K+) ATPase: evidence for a ligand-induced conformational change in the enzyme.

The phosphorylation of (Na+, K+)ATPase from the electric organ of the electric eel is dependent on Mg2+. The amount of phosphoenzyme formed was increased by K+ and decreased by Na+. Kinetic analyses indicate that a ternary complex of ATPase, Pi and Mg2+ is formed prior to phosphorylation of the protein. Calorimetric studies revealed extraordinarily large enthalpy changes associated with the binding of Mg2+ (-49 kcal/mol) and of Pi (-42 kcal/mol), indicating a thermodynamically significant conformational change in the enzyme. The dissociation constant for the binding of Mg2+ and Pi derived from calorimetric measurements is in good agreement with the value obtained from the kinetic studies. These results indicate that ion binding induces a conformational change in the enzyme which is a prerequisite for phosphorylation by Pi.


Heart phosphofructokinase: allosteric kinetics with fructose 6-sulfate.

The allosteric regulation of heart phosphofructokinase was studied at pH 6.9 with an alternative substrate, fructose 6-sulfate. The alternative substrate allowed kinetic studies to be carried out at high enzyme concentrations (0.1 mg/ml) where the effect of allosteric ligands on enzyme physical structure has been studied. A Km for ATP binding (8-10 muM) in the presence of saturating AMP concentrations was found which agreed well with the value obtained at pH 8.2, ATP inhibitory effects closely followed saturation of its substrate site. Hill plots for ATP inhibition gave an interaction coefficient of 3.5 indicating cooperatively between at least four enzyme subunits. Neither AMP nor fructose 6-sulfate affected the cooperativity between the ATP inhibitory sites but only increased the inhibitory threshold. As the ATP concentration was increased from suboptimal to inhibitory levels, interaction coefficients for AMP and fructose 6-sulfate changed from 1 to 2. Increasing citrate concentration resulted in an increase in the interaction coefficient for fructose 6-sulfate to a value of 1.9. Citrate inhibition was synergistic with ATP inhibition with an interaction coefficient of 2. The data indicate that  allosteric kinetics of the enzyme can be shown at high enzyme concentrations with the alternative substrate. ATP inhibition appears to involve interaction between at least four subunits, while citrate, AMP, and fructose 6-sulfate interact minimally with two subunits.


Mechanism of inhibition of relaxation by N-ethylmaleimide treatment of myosin.

It has remained unexplained why N-ethylmalaeimide (NEM) treatment of myosin can inhibit relaxation in actomyosin systems from rabbit skeletal muscle which appear to be regulated solely through tropomyosin and troponin. Since rigor complexes between (nucleotide-free) myosin and actin affect the tropinin-tropomyosin system, the possibility was explored that, as a result of NEM treatment, some of the myosin maintains rigor complexes with actin in the presence of ATP which might be responsible for inhibition of relaxation. Evidence is presented indicating that such a mechanism might account for the effects of NEM treatment. First, after exhaustive NEM treatment of heavy meromysin (HMM), acto-HMM complexes were no longer dissociated by ATP. Second, admixture of such NEM-treated, enzymatically inactive HMM or myosin to native regulated actomyosin or acto-HMM inhibited relaxation.


Myosin and actomyosin from human skeletal muscle.

Human skeletal natural actomyosin contained actin, tropomyosin, troponin and myosin components as judged by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. Purified human myosin contained at least three light chains having molecular weights (+/-2000) of 25 000, 18 000 and 15 000. Inhibitory and calcium binding components of troponin were identified in an actin-tropomyosin-troponin complex extracted from acetone-dried muscle powder at 37 degrees C. Activation of the Mg-ATPase activity of Ca2+-sensitive human natural or reconstituted actomyosin was half maximal at approximately 3.4 muM Ca2+ concentration (CaEGTA binding constant equals 4.4 - 10(5) at pH 6.8). Subfragment 1, isolated from the human heavy meromyosin by digestion with papain, appeared as a single peak after DEAE-cellulose chromatography. In the pH 6-9 range, the Ca2+-ATPase activity of the subfragment 1 was 1.8- and 4-fold higher that the original heavy meromyosin and myosin, respectively. The ATPase activities of human myosin and its fragments were 6-10 fold lower than those of corresponding proteins from rabbit fast skeletal muscle. Human myosin lost approximately 60% of the Ca2+-ATPase activity at pH 9 without a concomitant change in the number of distribution of its light chains. These findings indicate that human skeletal muscle myosin resembles other slow and fast mammalian muscles. Regulation of human skeletal actomyosin by Ca2+ is similar to that of rabbit fast or slow muscle.


Immunochemical studies on the large polypeptide of electrophorus electroplax (Na+ + K+)-ATPase.

Antibodies against Lubrol-solubilized Electrophorus electroplax (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) and its 96 000-dalton polypeptide (P96) were raised in rabbits. The P96 antibody does not cross react with the (Na+ + K+)-ATPase from mammalian species and tissues, but it cross reacts with the (Na+ + K+)-ATPase from both Electrophorus electroplax and brain. The combination of enzyme with anti-P96 is found  to inhibit phosphoryl enzyme formation to the same extent that it inhibits enzyme activity. The rate of K+-sensitive dephosphorylation of phosphoryl enzyme appears to be unchanged. These are also found to be true with the antibody against the whole enzyme. Upon tryptic digestion of the enzyme-anti-P96 complex only the large polypeptide of the enzyme is protected. In the case of enzyme-anti-Lubrol-solubilized enzyme complex, both the large and small polypeptides are protected, whereas preimmune sera are without any protecting effect. The data indicate that the phosphoryl acceptor polypeptide and the Lubrol-solubilized electroplax (Na+ + K+)-ATPase from which the polypeptide is derived are phylogenetically distinct from those of the mammalian (Na+ + K+)-ATPases. The selective tryptic resistance of the enzyme-anti-P96 complex indicates that the two polypeptides are spatially well separated, possibly on opposite sides of the membrane.


Comparative studies on amino and thiol groups in myosins from different sources.

Myosins from rabbit white and red skeletal, rabbit heart, fish skeletal and chicken gizzard muscles, as well as from human platelets were subjected to trinitrophenylation by trinitrobenzene sulfonate and alkylation by N-ethylmeleimide which affected their amino and thiol groups, respectively. The blocking of amino groups was carried out in the presence or in the absence of Mg-ADP and was followed both spectrophotometrically and enzymatically. Essential amino groups, whose modification throughly changes the enzymic characteristics of myosin, were found in heart and in all skeletal muscle myosins but were absent in myosins from chicken gizzard muscle and from human platelets. The reaction of these amino groups was highly retarded in the presence of Mg-ADP. Alkylation of thiols led to loss of the K+-activated ATPase (ATP phosphohydrolase, EC 3.6.1.3) in all myosins. However, the rate of loss of activity varied from one myosin to another and, for a given myosin, was affected by the presence of nucleotides and by the value of the ionic strength. The change in Ca(2+)-activated ATPase activity (ATP phosphohydrolase, EC 3.6.1.3) on alkylation was influenced by the presence of Mg - ADP during the reaction. In the absence of this nucleotide, the Ca(2+)-ATPase activity increased and reached a plateau as a consequence of modification. The extent of activation largely depended on the origin of the myosin. When alkylation was carried out in the presence of Mg-ADP, the Ca(2+)-ATPase activity as a function of time exhibited a maximum but the descending part of the curve was absent in myosins from heart and gizzard muscles.


Membrane-bound interferon specific cell receptor system: role in the establishment and amplification of the antiviral state.

The cell membrane, in addition to other functions, plays an important role in regulating cell metabolism governed by messenger proteins (or other substances) acting from the outside. The interferon receptor system located in the cell membrane (used as a model) might consist of two components: a binding site and an activator site. As shown by experiments based on competition between interferons for the same receptor, binding is not necessarily followed by activation of the antiviral state. It is possible that polysaccharid residues present in gangliosides play an important role in binding. A critical concentration of interferon molecules in contact with the receptors is needed to induce the antiviral state, which is thus a cooperative process. The activation and probably the amplification of the response require free membrane-bound energy and the integrity of the cytoskeletal components of the cell. Modifications in cell membrane structure can change the response to interferon; on the other hand, interferon might induce changes in the cell membrane which finally result in an altered response to toxins and, in some instances, in recovery of lost contact inhibition in transformed cells.


In vitro phagocytosis of Candida albicans by peripheral polymorphonuclear neutrophils of patients with recurrent infections:Case reports of serum-dependent abnormalities.

The "in vitro" phagocytosis of C. albicans by peripheral polymorphonuclear neutrophils (PMN) of 25 healthy subjects and of 27 patients with recurrent infections was performed in autologous serum and in normal pooled AB serum. In AB serum PMN of the patients phagocytosed C. albicans significantly better than PMN of healthy subjects. In 9 out of 27 patients the phagocytosis of C. albicans by the patient's PMN was markedly lower in autologous serum than in AB serum. Four patients with extreme serum-dependent abnormalities in the phagocytosis of C. albicans by their PMN's are described more in detail.


[Na, K-ATP-ase and acetylcholinesterase activity of the membrane structures of the rat brain and spinal cord during the seizure process].

The activity of ATP-ase and acetylcholinesterase (AChE) in crude mitochondrial fraction (CMF) and microsomal fraction of rat brain cortex and the spinal cord was studied in clonic seizures evoked by electroshock and 5 min after them. Inhibition of the Na, K-ATP-ase activity of the CMF of the brain at the clonic phase of convulsions and an increase in the activity of this enzyme in all the fractions of the tissues under study at the postconvulsive period were revealed. The activity of Ca-ATP-ase in the CMF of the brain increased during the convulsions and decreased at the postconfulsive period. The activity of Mg-ATP-ase remained unchanged. The AChE activity, as a rule increased during the convulsions, and grew even more during the postconvulsive period; the spinal cord tissue displayed a reduction of the activation effect. A possibility of structural reconstructions in the excitable neuron membranes during the convulsive activity is discussed.


[Mechanism of inhibition of the glycolytic activity of the myocardium during the early postnatal period].

Reduction of the activity of glycolysis and glycogenolysis regularly observed in the developing cardiac muscle was not associated with reduction of the glycolytic system, but was due to the regulatory inhibition of the phosphofructokinase link in the glycolytic link. This was indicated by a 4.5-fold increase in the rat heart of the ratio of the active masses of the phosphofructokinase reaction in the course of 2 weeks of the postnatal development.


Activity in vitro of ten antimicrobial agents against Neisseria gonorrhoeae. A study of the correlation between the sensitivities.

105 Belgian strains of Neisseria gonorrhoeae were tested for their sensitivity to penicillin, ampicillin, rifampicin, erythromycin, tetracycline, streptomycin, spectinomycin, sulphamethoxazole, trimethroprim, and a combination of sulphamethoxazole and trimethroprim in a 5:1 ratio. Distribution and median values of minimum inhibitory concentrations (MICs) are given and discussed. 42 per cent. of strains were relatively resistant to penicillin (MIC greater than or equal to 0-04 mug/ml.), but only 2 per cent. showed high-level resistance (MIC greater than or equal to 0-38 mug/ml.), which is comparable with the prevalence of decreased sensitivity found in other European countries. A significant positive correlation (P less than or equal to 0-01, rank correlation coefficient) is found between the sensitivities to penicillin, ampicillin, erythromycin, tetracycline, and streptomycin, except for the ampicillin-erythromycin and ampicillin-tetracycline pairs. Rifampicin is correlated with tetracycline. No correlation is found between the sensitivities to spectinomycin and any of the other drugs. The combination of sulphamethoxazole and trimethoprim in a 5:1 ratio also shows a significant positive correlation with penicillin and ampicillin and with sulphamethoxazole and trimethoprim separately.


Nuclear suppressors of the [poky] cytoplasmic mutant in Neurospora crassa. I. Genetics and respiratory properties.

Six nuclear suppressors of the (poky) cytoplasmic mutant (sup-1, sup-3, sup-4, sup-5, sup-10, sup-14) have been obtained in Neurospora crassa. The sup genes suppress the slow growth phenotype of (poky), and alleviate, at least partially, the deficiency of cyanide sensitive respiratory activity in the mycelium of this cytoplasmic mutant. The six suppressors are nonallelic, suppress the phenotypic effects of (stp-Bl) in addition to (poky), but have no effect on the phenotype expression of the (mi-3) cytoplasmic mutant. On the basis of experimentally established molecular defects in (poky) and on the basis of hypothetical consideration, it is proposed that the sup mutations affect the structure and properties of mitochondrial ribosomal proteins.


The significance of low back pain in older adults.

A retrospective study of the practice of an orthopedic surgeon at a university teaching hospital was done to evaluate the significance of low back pain in older adults. All 259 patients in a 3-year period 50 years of age and over whose presenting complaint was low back pain or sciatica or both were identified and classified by final diagnosis. A comparison was similarly identified and classified. Systemic disease, particularly cancer, was much more prevalent in the older group. It was demonstrated that a simple screening routine consisting of measuring the erythrocyte sedimentation rate and serum concentrations of alkaline phosphatase and calcium would identify all cases of unsuspected malignant disease--that is, at least one of the values would be abnormal in every case.


Low back pain in the workman in Canada.

Groups of 25 Workmen's Compensation Board patients (WCP group) and 25 non-Workmen's Compensation Board patients (NWCP group) hospitalized because of low back pain were compared. The WCP group had a significantly higher male:female ratio, incidence of sudden onset and precipitating factors, and prevalence of weakness, decreased reflexes and sensory loss. Surgical treatment and multiple operations were significantly more frequent in the WCP group, as was complete long-term relief or worsening after operation. Adequate partial relief was significantly more frequent in the NWCP group. The differences suggest more severe conditions in the workmen. Prevalence of psychological factors was not significantly different, although a trend was observed for this to be greater in the WCP group.


Plasma amino acids in patients with the carcinoid syndrome.

Plasma tryptophan (Trp) is reported to be decreased in some patients with the carcinoid syndrome. To determine if the plasma levels of other amino acids are also altered in the carcinoid syndrome, we used a fas-liquid chromatographic method to determine the plasma amino acid concentration of nine patients with the carcinoid syndrome and nine age-matched healthy control subjects. In comparison to the control subjects, the patients with the carcinoid syndrome had decreased plasma concentration of valine (Val), isoleucine (Ile), lysine (Lys), and ornithine (Orn), and an increased plasma concentration of methionine (Met). With the exception of a decrease in urinary excretion of proline (Pro) and hydroxyporline (Hyp), the patients with the carcinoid syndrome had normal quantities of amino acids in their urine. Plasma Met returned to normal when serotonin production by the tumor was reduced 60% by parachlorophenylalanine (PCPA); the other amino acid abnormalities persisted. Further studies are needed to determine the significance of these amino acid abnormalities.


Pharmacology of antitumor agents from higher plants.

Some pharmacologic properties of nine antitumor agents from higher plants are described. The agents are vincristine, vinblastine the epiodophyllotoxin derivatives VM-26 and VP-16-213, maytansine, bruceantin, thalicarpine, camptothecin, and lapachol. When sufficient information is available, the agents are discussed with regard to their antitumor activity, mechanism of action, pharmacologic disposition, structure-activity relationships, and toxicity.


Effect of digitoxin on cardiac hypertrophy induced by pericardiectomy and exercise.

Removal of the pericardium in combination with a mild exercise programme of swimming resulted in a significant increase in heart weight and heart weight/body weight ratio of young rats. Heart weight/body weight ratios were 3.46+/-0.25 in the sedentary control animals, 4.16+/-0.26 in pericardiectomized animals swimming 2 h each day, and 4.60+/-0.22 in pericardiectomized animals swimming 6h/d. The effect of pericardiectomy on the development of cardiac hypertrophy is additive to that of mild exercise (2h/d) but not to prolonged exercise (6h/d). The administration of digitoxin significantly decreased the development of cardiac hypertrophy in pericardiectomized animals that were exercised for 2 h/d but not those exercised for 6 h/d. These findings further substantiate the physiological effect on the heart of the pericardium. The effects of pericardiectomy should be considered in experimental studies of cardiac hypertrophy and in clinical studies involving cardiac surgery.


Myocardial sarcolemmal ATPase in dogs with induced mitral insufficiency.

A study of the sarcolemmal Na+K+ATPase in the left failing heart due to induced mitral insufficiency was made in dogs. The sarcolemmal Na+K+ATPase markedly increased in the failing left ventricle. There was no change in the ATPase in the nonfailing right ventricle of the same dog. It was observed that during the early period of mitral incompetence, when there was an increase in the index of myocardial contractility, there was also a decrease in the sarcolemmal Na+K+-ATPase activity. There was no change in the MPG++-ATPase of the sarcolemmal fractions of either the failing or nonfailing ventricle. These results indicate that sarcolemmal Na+K+-ATPase appears to be involved in the reduction of the myocardial contractility during heart failure.


Surface glycosaminoglycans as a differentiation cofactor in neuroblastoma cell cultures.

The possible role of surface glycosaminoglycans (GAGs) in neuronal maturation occuring in neuroblastoma cultures has been investigated. GAGs of neuroblastoma cells, grown in suspension and monolayer, were labelled with 3H-glucosamine and 35S-sulfate. Neuron maturation, following cell adhesion to culture dishes, is accompanied by an increased ability of the cells to retain heparan sulfate (HS) on their surface, which is otherwise lost into the culture medium. The role of surface HS as a cofactor of cellular differentiation is discussed.


Changes in the stimulatory capability of mouse small thymocytes to give a proliferation of allogenic spleen cells during differentiation.

Our previous studies on surface antigenic properties of murine small thymocyte subpopulations raised the hypothesis that some of the least dense cells, which possibly were precursor T cells, differentiated into the most dense cells which have the properties of mature T cells. Thus, the stimulatory capacity of the least dense was compared with that of the most dense by one-way mixed leukocyte culture. A marked difference in capacity between both subpopulations was found, i.e., the capacity of the least dense was the strongest of all subclasses, whereas that of the most dense was the weakest. It was concluded from discussions on this difference that the finding supported the hypothesis.


[Perfection of an experimental schedule for the quantitative evaluation of trans-abscissic acid by biological tests].

Using gas-liquid chromatography, we have studied the kinetics of the isomerization from trans-ABA to cis-ABA under the effect of short ultraviolet-light (254 nm). At first, for a given volume, the conditions required to reach 50% isomerization were determined. Then the method was adapted to the use of extracts. It is thus possible to estimate the amount of trans-ABA in extracts with a suitable biological test.


[The role of distinct membrane components of the enzyme in the ouabain sensitivity of Na+/K+ ATPase].

Purified plasma membranes from a cell line derived from the murine plasmocytoma MOPC 173 exhibited a 50% inhibition of the Na+K+ ATPase by 120 muM ouabain. EDTA treatment of such membranes induced a drop in the ouabain concentration needed for 50% inhibition to 0.4 muM. Supernatants obtained after EDTA treatment were able to complement with Ca(++) + Mg++ the washed EDTA treated membranes which recover their original resistance.


Hemodynamics after surgical repair with right ventricle to pulmonary artery conduit.

To assess the results of cardiac repair utilizing a right ventricular to pulmonary artery conduit, we reviewed postoperative hemodynamic data in 16 patients catheterized 0.5 to 5 years after repair. In 12 patients, a Hancock conduit (dacron conduit with porcine valve) was used; the conduit in the remaining four patients was made with an aortic homograft. All patients in whom an aortic homograft was utilized developed severe obstruction and calcification of their graft. The majority of patients, 9/12, with a Hancock conduit, had only mild to moderate conduit obstruction; the remaining three had severe obstruction (gradients greater than 70 mm Hg). The sites of Hancock conduit obstruction were at the distal end of the conduit in 8/12, proximal end of conduit in 6/12, and at the porcine valve in 4/12 patients. The data suggest that repair with a Hancock conduit is hemodynamically more satisfactory than with aortic homograft.


Relationship between right ventricular muscle bundles and pulmonary valve. Significance in pulmonary atresia with intact ventricular septum.

The normal pulmonary valvular cusps and related sinuses lie superimposed upon specific muscle bundles of the right ventricular infundibulum. Most prominent of such muscle bundles are those related to the right and left (posterior) pulmonary valvular cusps and sinuses. Least prominent is the muscle bundle related to the anterior pulmonary cusp and sinus. In pulmonary valvular atresia with intact septum the normal relationships are accentuated by right ventricular hypertrophy. A transpulmonary valvotomy done either through the region of the right or left (posterior) cusp tends to extend through subjacent muscle. The opening made through the region of the anterior cusp is more apt to lead directly into the right ventricular cavity.


Developmental training by parents of the very young child with potential handicap.

Fifteen children aged 9 to 15 months, who were on the observation register of a city, and considered to be showing signs of delayed development, were studied over a 3-month period. Following assessment, the parents were shown ways in which they could train their children appropriate to their development levels, in separate fields of locomotion, social development, language, and hand-eye coordination. Eight out of 13 children with delay showed significant improvement in general quotients of development over the 3 months. This occurred in 5 out of 7 children with no signs of neurological abnormality at the time of the study, and in 3 out of 6 children with signs of neurological disorder. Two children without delay showed no significant improvement. Parents' reactions are discussed, and a description is given of the way in which this project was designed, suggesting implications for future implications for future Community Health services.


Hypertrophic cardiomyopathy. Evaluation by gated cardiac blood pool scanning.

The gated radionuclide cardiac blood pool scan (GCS) can be used to visualize the entire profile of the interventricular septum and left ventricular contraction. Twenty-two patients with hypertrophic cardiomyopathy, nine with valvular aortic stenosis and six normals, underwent echocardiography and GCS. All patients with hypertrophic cardiomyopathy had asymmetric septal hypertrophy and 14 of 22 had resting systolic anterior motion of the anterior leaflet of the mitral valve on echocardiogram. In eight patients with aortic stenosis with adequate echocardiograms, two had asymmetric septal hypertrophy and none had systolic anterior motion. The GCS demonstrated disproportionate upper septal thickening in 11; septal flattening in 16; cavity obliteration in 17; and a filling defect in the region of the left ventricular outflow tract in 16 of the 22 patients with hypertrophic cardiomyopathy. In the nine patients with valvular aortic stenosis, two demonstrated septal flattening, two cavity obliteration, two an outflow tract defect, and none disproportionate upper septal thickening. Both patients with cavity obliteration demonstrated asymmetric septal hypertrophy on echocardiogram. One normal control patient had septal flattening. Thus the gated cardiac blood pool scan provides an atraumatic technique for the evaluation of patients with hypertrophic cardiomyopathy which complements the echocardiogram.


Special unit care of the preschool child with severe physical or mental handicaps.

The provision of special care units for the severely physically and mentally handicapped preschool child is discussed. Types of handicap and ethnic origin of the children passing through such a special care unit in a two year period are considered. Management of the special care unit is discussed and the need for a multidisciplinary approach to the care of the child emphasized.


A methodology for establishing a diagnostic index for syndromes of unknown etiology.

A method has been developed to test for heterogeneity in syndromes of unknown etiology and to distinguish between patients with and without the syndrome. The validity of the method was tested on a group of patients suspected of having a syndrome that can be diagnosed by other means (Down syndrome), and was found to be effective. The method was then applied to a group of patients suspected of having a syndrome of unknown etiology (de Lange). It was shown that the group appears to be heterogeneous. A preliminary diagnosis of having or not having the syndrome was made in about 80% of the patients.


Early education for handicapped children.

Early education is an integral part of daily living. Early "special" education for handicapped children involves adapting the daily living environment to enable each individual child to make the optimum use of such ability and development potential as he has. Parents are the first and most important educator s of their children. It is the role of professional people to guide this early education via the parents. Early assessment, as a basis for such educational planning is discussed in general terms.


Spontaneous and PHA-induced rosetting of human blood, tonsil lymphocytes and MLC blasts with sheep, human and horse erythrocytes.

Compared to peripheral blood lymphocytes the ability of human tonsil T cells and MLC blasts to bind sheep, human and horse erythrocytes was found to be increased. Tonsil and MLC T cells were able to bind sheep red blood cells without any cold incubation, i.e. they were 'early' rosettes, and higher percentage of human and horse erythrocyte rosettes were formed by these cells. Low doses of phytohaemagglutinin increased the proportion of rosettes between peripheral blood, tonsil, MLC cells and human and horse erythrocytes. PHA acted only on T cells, and not on B cells, lymphoblastoid B and other cell lines. On the ground of the stronger rosetting property of MLC blasts and tonsil cells, it is likely that the T cells responsible for binding of horse and human erythrocytes after PHA treatment are 'early' or 'active' rosetting cells.


Evidence for immune complexes involving anti-lymphocyte antibodies associated with hypocomplementaemia in chronic lymphocytic leukaemia (CLL).

Unmeasurable total haemolytic complement (C) was observed in serum of a patient with untreated chronic lymphocytic leukaemia and recurrent non-hereditary angioedema. Analysis of C components immunochemically demonstrated a marked reduction of C1q and C1s inhibitor, undetectable C1r, C1s and an elevated B. Haemolytic C1, C4 and C2 were less than 5 percent of normal, functional C1s inhibitor was absent. Cryoglobulin and C1q precipitins were present in the serum. Of special interest was the presence of high levels of cold-reactive antilymphocyte antibody, determined by both C-dependent cytotoxicity and indirect immunofluorescence. The antibody exhibited specificities for both autologous lymphocytes and lymphocytes from normal donors; cytotoxic activity for autologous leukaemia cells was removed by absorption with normal isologous tonsil lymphocytes. Specific enrichment of this antibody relative to the serum level was demonstrated in the cryoglobulin and its isolated 19S fractions. Free lymphocyte surface antigen was also demonstrated by gel diffusion using specific rabbit antilymphocyte antiserum. These data strongly suggest the presence of pathogenetically significant circulating complexes of lymphocyte surface antigen and specific antibody in certain patients with CLL.


Elimination and serum protein binding of phenylbutazone in patients with renal insufficiency.

In uremic patients the serum protein binding of phenylbutazone was significantly decreased. The concentration of the dialyzable drug estimated by equilibrium dialysis was increased by 117-1100% (mean +/-SD = 502 +/- 236%). No correlation exists between the serum protein binding of phenylbutazone and the concentration of serum albumin, urea and creatinine. The serum protein binding of glymidine was also decreased in the uremic patients (dialyzable fraction increased by 214%). The apparent plasma levels of phenylbutazone immediately after its ingestion (600 mg per os) were decreased in uremic patients (44.5 +/- 11 mug/ml) in comparison with healthy subjects (66.3 +/- 17.3 mug/ml). The half life of phenylbutazone was decreased in the uremic patients (41.7 +/- 12.4 hr) in comparison with healthy volunteers (58.9 +/- 14.9 hr). It is suggested that the accelerated elimination of phenylbutazone in uremic patients is caused by an altered distribution of the drug caused by its decreased serum protein binding.


Dityrosine in collagen.

Dityrosine was formed by the action of peracetic acid and sodium peroxide on soluble collagens. Dityrosine was also detected in native insoluble collagen, but only from old animals. Dityrosine was identified by amino acid analysis, fluorescence absorption and mass spectra.


Fibroblast DNA synthesis activation in sponge induced granulation tissue. The effect of antineutrophil serum and cyclophosphamide.

DNA synthesis in rat and rabbit polyvinyl sponge induced granulation tissue has been studied using thymidine (methyl-3H). Synthesis was determined by measurement of thymidine incorporation into cold trichloroacetic acid insoluble material and by autoradiography. Granulation tissue was removed and immediately incubated in vitro in the presence of thymidine (methyl-3H) for three hours. The label was incorporated into the nuclei of fibroblasts and, to a lesser extent, of endothelial cells. The labeled material was 93% lysable by DNase and its synthesis was inhibited by hydroxyurea and bleomycin. In this system synthesis was linear for two hours and then ceased. A marked increase in DNA synthesis occurred in tissue harvested at 44 hours after sponge implantation. This rise was confirmed by autoradiographic studies which showed an increase in nuclear labeling at two days after implantation. Neutropenia produced by injections of antineutrophil serum or cyclophosphamide failed to inhibit activation of DNA synthesis in fibroblasts or endothelial cells. Amonocytosis also had no effect on this process. Rates of thymidine incorporation into DNA and thymidine phosphates in vivo were similar to those found during in vitro incubations of granulation tissue.


A simple microassay of prolyl hydroxylase applicable to skin punch biopsy specimens.

A method is described for the assay of prolyl hydroxylase. The method is rapid, avoids the use of vacuum distillation equipment and can be applied to small tissue samples such as skin biopsies.


Auto-immunological basis of disk degeneration.

Ninety-four subjects were divided into 5 groups according to symptoms and radiologic findings to devise a test for immunoglobin levels and lymphocyte microstimulation. Cellular immunity to disk antigens can be demonstrated in disk degeneration which may be primary or secondary. The serum level of IgM, irrespective of the age of the individual was significantly higher in patients with backache than asymptomatic patients.


Neuroleptic induced extrapyramidal symptoms.

All currently marketed neuroleptics induce extrapyramidal symptoms (EPS). These EPS are a function of biological sensitivity, neuroleptic molecular structure, dose, age, sex, and duration of neuroleptic treatment. Because of their association with EPS, at times irreversible, and their modest efficacy in the non-schizophrenic patients, neuroleptic administration should be limited predominantly to schizophrenic patients. Furthermore EPS should not be used as a guideline for the efficacy of neuroleptics as formerly assumed. For EPS may occur at subtherapeutic doses of neuroleptics and may be absent in patients experiencing clinical response. Neuroleptic dose should be the lowest efficacious dose required to provide symptom remission. In addition, antiparkinsonian (AP) agents should be administered predominently contraactively and not routinely in combination with neuroleptics. With the judicious administration of neuroleptic agents and AP medication, distressing EPS can be prevented or minimized, while providing control of schizophrenic symptoms.


Estrogen (EB) and EB + progesterone (P) induced changes in pituitary sodium, potassium adenosine triphosphatase activity (ATPase).

Estradiol-benzoate (EB) injected into previously ovariectomized (OVX) rats, increased pituitary ATPase activity 69% over controls, within one hour of treatment. Twelve hours after injection, ATPase activity was not significantly different from controls. Progesterone [(P): 5mg/100gBW] administered in conjunction with EB elicited an analogous response. AT at time of EB and EB+P induced increments in pituitary ATPase activity, plasma LH levels were dramatically reduced to normal, intact diestrous control levels. Post-castrational elevations in FSH were also suppressed after one hour of treatment with EB, but not following EB+P administration. The results suggest that the inhibitory actions of EB and EB+P on post-castrational LH levels may be related to modulation by these steroids of pituitary membrane ATPase activity.


Suprahepatic interposition of the colon in association with Down's syndrome: report of a case.

A patient in whom suprahepatic interposition of the colon was found with primary trisomy 21 (Down's syndrome) is described. While both syndromes are rare, their coincidental occurrence in the same patient has not been previously reported. The possibility that a chromosomal abnormality may exist in patients who have suprahepatic interposition of the colon is entertained.


Subcutaneous, isogeneic transplantation of either duct-ligated pancreas or isolated islets in streptozotocin diabetic mice.

Recovery from hyperglycemia was observed in streptozotocin diabetic mice that received subcutaneous, isogeneic transplants of either isolated islets or duct-ligated pancreas. Transplants of isolated islets obtained from collagenase-digested adult pancreas provided recovery from hyperglycemia, but the incidence of recovery depended on the amount of islet tissue initially transplanted. Hyperplastic, insulin-rich islets obtained from the pancreas of obese hyperglycemic mice (ob/ob) allowed recovery between 3 and 6 weeks, whereas an equivalent number of islets obtained from non-obese, normal donors gave only partial recovery after 8 weeks. Implantation of pancreatic endocrine tissue obtained from adult donors whose pancreatic ducts were ligated several weeks earlier, led to consistent recovery within 8 to 10 weeks. The content of immunoreactive insulin (IRI) extracted from transplants of mice recovering from hyperglycemia was 16 to 19% of that found in the normal mouse pancreas and was about 4 times greater than that remaining in the recepient's own pancreas. Transplants removed from hosts that did not recover contained a relatively small amount of IRI indicating that these transplants contained insufficient insulin stores to allow recovery form hyperglycemia.


Some properties of thyroidal membrane adenosinetriphosphatase and iodide uptake: effects of basic polyamino acids.

Poly L-lysine, poly L-ornithine, and histone significantly inhibited the iodide uptake by the thyroid slices, as previously reported. These basic polymers diminshed Na, K-ATPase and concomitantly markedly elevated Mg-ATPase activity in the NaI-treated microsomal preparation and the plasma membrane fraction obtained from thyroid. Poly L-glutamic acid, which was noneffetive to the iodide uptake in vitro, did not show such phenomenon. K-dependent p-nitrophenylphosphatase activity which is considered to reflect the terminal step of the reaction sequence of Na, K-ATPase was also inhibited by poly L-lysine. The effects mentioned above of poly L-lysine and other basic polyamino acids on membrane ATPase system were only found in the preparations from thyroid. The inhibitory effect of these reagents on thyroidal iodide uptake was discussed in terms of the change in membrane ATPase activities.


Salt inactivation as a mechanistic probe of membrane-bound chloroplast coupling factor 1.

Conditions are reported under which ATP protects membrane-bound coupling factor 1 against sodium bromide inactivation. The presence of Mg2+ was found to be obligatory for this protection. ADP and GTP also protected the enzyme against salt inactivation but to a much smaller extent. Other nucleotides tested were ineffective. At low ATP concentrations ADP prevented the effect of ATP and modified the saturation curve for ATP from hyperbolic to sigmoidal. Treatment of chloroplasts with 0.4 M MgCl2 or 2 M LiCl resulted in inactivation of photophosphorylation. In contrast to NaBr-depleted particles the MgCl2 or LiCl-depleted chloroplasts can be reconstituted by purified coupling factor 1. A binding site for Mg2+ and two different sites for ATP upon the coupling factor 1 are suggested to explain the mechanism of their protection against salt inactivation.


Identification and some properties of a new fast-reacting plasmin inhibitor in human plasma.

Fresh plasma was seeded with trace amounts of highly purified biologically intact iodine-labelled plasminogen and the plasmin-inhibitor complexes formed after activation with streptokinase or urokinase separated by gel filtration. Two radioactive peaks were observed, the first one eluted in the void volume and the second one just before the 7-S globulin peak. In incompletely activated samples, the second peak was always predominant over the first one. Both components were purified with high yield by a combination of affinity chromatography on lysine-agarose and gel filtration, and investigated by dodecylsulphate-polyacrylamide gel electrophoresis and immunoelectrophoresis. Neither component reacted with antisera against alpha1-antitrypsin, antithrombin III, C1-esterase inhibitor, inter-alpha-trypsin inhibitor or alpha1-antichymotrypsin. The component of the first peak appeared to be a complex between plasmin and alpha2-macroglobulin which reacted with antisera against human plasminogen and against alpha2-macroglobulin. The component of the second peak had a molecular weight (Mr) of 120000-140000 by dodecyl-sulphate-polyacrylamide gel electrophoresis and lpon reduction displayed a doublet band with an Mr of 65000-70000 and a band with Mr 11000. It reacted with antisera against plasminogen and with antisera raised against this complex and absorbed with purified plasminogen. The latter antisera reacted with a single component in plasma which is different from the above-mentioned plasma protease inhibitors. Specific removal of this component from plasma by immuno-absorption resulted in disappearance of the fast-reacting antiplasmin activity whereas alpha2-macroglobulin was found to represent the slower-reacting plasmin-neutralizing activity. In the presence of normal plasma levels of these proteins, the specific removal or absence of alpha1-antitrypsin, antithrombin III or C1-esterase inhibitor did not alter the inactivation rate of plasmin when added to plasma in quimolar amounts to that of plasminogen. It is concluded that only two plasma proteins are important in the binding of plasmin generated by activation of the plasma plasminogen, namely a fast-reacting inhibitor which is different from the known plasma protease inhibitors and which we have provisionally named antiplasmin, and alpha2-macroglobulin, which reacts more slowly.


Comparison between strontium and calcium uptake by the fragmented sarcoplasmic reticulum.

The ATP-supported uptake of strontium by the fragmented sarcoplasmic reticulum is monophasic and proceeds more rapidly than the fast uptake of calcium. Strontium uptake is not activated by Pi. The accumulation of strontium is nearly proportional to the external strontium concentration even in the millimolar range. Internal and external strontium quickly equilibrate. One mole of strontium is stored for every mole of ATP split by the Sr2+-activated ATPase. In the absence of oxalate most of the strontium is taken up with a transport ratio of one. On the opposite, the transport ratio of calcium decreases immediately, especially when ADP is not instantaneously phosphorylated to ATP. In this case, energy conversion is uncoupled more effectively by the simultaneous action of ADP and free internal calcium, resulting in the interruption of the fast uptake. After depletion of ATP most of the stored strontium is released and the remaining fraction appears to be not exchangeable. Strontium activates the slow uptake of calcium, but reduces the amplitude of the fast uptake. The calcium induced release of strontium, and vice versa, is partial and transient. The strontium activated ATPase does not transport calcium at low ionic calcium concentrations.


Study of the excitability cycle of the blink reflex in Huntington's chorea.

The trigemino-facial reflex was studied in 7 patients affected by Huntington's chorea and in 10 patients affected by Parkinson's disease. The results show a different behavior of the habituation phenomenon in the two groups of patients: it is enhanced in the choreic and abolished in the parkinsonian patients. The main changes concern the time course of the second phase (the first inhibitory phase) of the reflex excitability cycle, in fact, the inhibitory phase appears very pronounced and prolonged in huntingtonian patients and reduced or abolished in parkinsonian patients. Some pathophysiological mechanisms involved in the control of the trigeminofacial reflex excitability are discussed with particular regard to the role of the hemispheric structures.


Cellular responses to murine alloantigens of the major histocompatibility complex: the role of cell subpopulations that express different quantities of H-2 associated antigenic markers.

Subsets of lymphoid cells that function in the initiation and differentiation of cell-mediated responses to H-2-coded alloantigens were defined with an antiserum raised between congenic resistant lines of mice that differed for a limited number of components of the H-2 complex. Only those cells that express "Ia markers" can stimulate responses to H-2K, D and/or I region antigens in mixed lymphoid cell cultures, even though all lymphoid cells apparently express the H-2K and H-2D-coded private antigens. Ia markers, therefore, serve to distinguish the subset of cells which includes as its members the stimulating cells. The Ia marker(s) is expressed on the cell membrane of at least one of the two T cell subsets that collaborate in the development of T effector cells to H-2-associated alloantigens, i.e. precursors and helpers. The cells remaining after lysis with our antiserum plus complement no longer can respond in the MLR. Syngeneic non-T cells cannot reconstitute the response. Most activated and proliferating cells express the Ia determinant(s). A proportion of T effector or killer cells, however, does not express the Ia markers. We suggest, therefore, that the MLR-responsive cell in normal lymph nodes is an "activated" cell and the "Ia markers" are involved in the differentiation of T precursor to T effector cells. The end stage T effector probably is devoid of the Ia marker.


Lymphocyte-mediated cytotoxicity against tumor cells. III Differentiation of concanavalin A-activated cytotoxic effector cells.

The maturation of selected T cell responses in the lymphoid organs of irradiated CBA mice was followed after adoptive transfer of syngeneic fetal liver cells. Mitogenic responsiveness to phytohemagglutinin (PHA) and concanavalin A (Con A) was found to reach control values 3 weeks after reconstitution in the thymus, spleen, and lymph node, of fetal liver repopulated animals. Spleen and lymph node cell reactivity in mixed lymphocyte culture reactions required 6 weeks to reach significant values. However, the ability of spleen cell suspensions to be activated by Con A into cytotoxic effector lymphocytes appeared after only 2 to 3 weeks. It is concluded that two functionally distinct T cell subpopulations exist in the spleen, one which can be activated into cytotoxic effector lymphocytes by Con A, and one which responds to alloantigens by DNA synthesis.


Effects of prolonged ethanol administration on the noradrenaline levels of rat heart.

The effect of prolonged administration of ethanol on the noradrenaline concentration of the heart was investigated in rats. After 4 weeks there was no difference in the catecholamine levels between control and ethanol consuming rats. After 12 and 24 weeks there was a highly significant increase in heart noradrenaline concentration in hearts of experimental rats. These findings may indicate a delay in the effect of ethanol in cardiac tissue. It is further suggested that continued exposure to high levels of catecholamine may play a role in the development of cardiomyopathy in chronic alcoholism.


Effect of biogenic amines and GABA on ATPase activities in mouse tissue.

ATPase activities were studied in brain, kidney and liver (13,000 X g pellet) fraction from the mouse. Dopamine and norepinephrine added in vitro showed a dose-dependent stimulation of Na+ and K+ activated and oligomycin sensitive Mg2+ ATPase activities in brain but not kidney and liver tissue fractions. GABA and serotonin had no effect on ATPase in brain, but inhibited oligomycin sensitive Mg2+ ATPase activities in kidney and liver. The relationship between the enhancement of ATPase activity by neurotransmitters in brain and the neuronal excitation is discussed.


Ultrastructural cytology of regenerating tendon--an experimental study.

Cellular differentiations in regenerating tendon tissue of rats and guinea pigs were examined by the aid of the electron microscope. Fibroblasts with certain variations were found as basic cell types. Corresponding to the organelle composition classical fibroblasts, fibroblasts with histiocyte-like features and fibroblasts with myoide differentiations (comparable to the so-called myofibroblasts) were identified. Furthermore, proliferating capillaries with remarkable pericytic activities among other things producing fibroblast-like features must be mentioned. This fact led to the conclusion, that a part of fibroblasts in the proliferating connective tissue during tendon repair may derive from pericytes. Our ultrastructural investigations showed proof of the great plasticity of fibroblasts which function as stem cells in connective tissue regeneration.


Regional and subcellular distribution of superoxide dismutase in brain.

Superoxide dismutase has been found to be widely distributed and of approximately the same specific activity in all regions of human brain examined. It is not reduced during degeneration of the basal ganglia in Huntington's Chorea. After subcellular fractionation of human and guinea-pig cerebral cortex, the highest specific activity of the enzyme was found in the soluble fraction.


The central tubuli in distal segments of olfactory cilia lack dynein arms.

By means of the tannic acid-glutaraldehyde fixation method, the lack of dynein bridges between the central two tubuli in distal segments of mouse olfactory cilia is demonstrated. Consequently, these organelles are supposed to be unable to beat actively, in contrast to the proximal ciliary shafts.


Plasma insulin response to glibornuride in thyrotoxicosis.

The glycemic and insulinemic response to i.v. glibornuride injection has been studied in a group of 8 euthyroid subjects and in a group of 9 thyrotoxic patients before and after reserpine treatment. In thyrotoxic patients sulfonylurea did not lower blood glucose more than in normal subjects. The plasma insulin response, however, was definitely higher than that of the controls in the first few minutes; after the 20th minute, however, levels of insulinemia were not appreciably different in the two groups. Insulin delivery rate was greater in hyperthyroid patients than in the controls. Administration of reserpine for a few days, did not modify either insulin response or blood glucose fall in thyrotoxic patients.


Metabolic and morphologic studies in intraportal-islet-transplanted rats.

The intraportal injection of 350 to 1,000 isolated islets into streptozotocin-diabetic rats immediately normalized (approximately 24 hours) fasting plasma glucose and insulin levels. Polyuria, polydipsia, and hyperglucagonemia disappeared more gradually over a 2-to-12-week period--the time required for normalization varying with the severity of the diabetes and the number of islets transplanted. In long-term islet-transplanted rats (greater than five months), the hepatic insulin and glucagon reserves averaged 50 per cent and 25 per cent, respectively, of the corresponding normal pancreatic hormone content. Glucagon was increased slightly in the pancreas of streptozotocin-diabetic rats and decreased considerably in transplanted animals. However, total pancreatic glucagon (i.e. pancreatic and hepatic reserves) in transplanted animals was the same as the pancreatic content of normal control rats, indicating the presence of feedback control mechanism(s) in the regulation of pancreatic glucagon reserves. Long-term transplanted islets demonstrated well-granulated A-, B-, and D-cell movement out of the vascular space and the formation of narrow intercellular spaces and junctional complexes with surrounding hepatocytes.


Abnormal glucose tolerance and arginine tolerance tests in Huntington's disease.

Neuropathological studies of Huntington's disease reveal neuronal atrophy, lipofuscin accumulation and other findings characteristic of the aged brain, although the onset of disease is only the fourth decade. The pathology is limited to specific areas such as the caudate nucleus, cerebral cortex and hypothalamus. 14 patients with documented Huntington's disease (mean age of 44.4 years with a range of 27-79 years) were studied by oral glucose tolerance tests (GTT) and intravenous arginine tolerance tests performed under standardized metabolic conditions. Seven of the 14 patients had impaired carbohydrate tolerance. Mean plasma glucose level at 2h was 90.4+/-6.2 mg/100 ml in the patients with a normal GTT and 148.1+/-8.9 mg/100 ml in the patients with a diabetic type GTT. Mean peak insulin level in the nondiabetic group occurred at 1/2 h and was 60.2+/-10.1 muU/ml, but in the diabetic group the peak insulin level occurred at 2h and was 155.9+/-33.8 mgU/ml. There was failure of suppression of growth hormone during the GTT, with a rise to abnormally high levels at 5h (18.6+/-5.6 ng/ml). Arginine infusion resulted in normal glucose and insulin rise in the nondiabetic patients with Huntington's disease. However, arginine infusion provoked an elevated insulin response in those with a diabetic GTT, and an exaggerated growth hormone response in the majority of the patients. It is uncertain whether these observations are related to abnormal cerebral aging per se, direct hypothalamic neuronal degeneration, or perhaps a relative imbalance of intracerebral neurotransmitters including dopamine.


Cytochemical study of adrenal medulla of pigeons exposed to high altitude.

The concentration of adrenomedullary catechol hormones along with various types of mucopolysaccharides was studied in groups of control pigeons kept at sea level and in those exposed to high altitudes (1150,3490 and 4880 m, at 24, 8 and 2 degrees C respectively) of the Himalayan range. The exposed birds displayed an appreciable depletion of noradrenaline and periodate-reactive neutral mucopolysaccharides was noted, whereas the basophilia of the adrenomedullary tissue resulting from the presence of by weakly acidic muco-substances was slightly increased. The significance of these findings is discussed.


[Experimental studies on anthelmintics (XXVI). Biochemical and pharmacological studies of 4-iodothymol on Ascaris lumbricoides suum].

We have shown previously that 4-iodothymol (IT) produces a contraction in Ascaris muscle, probably due to the myogenic action. In this paper, the effects of IT on the carbohydrate metabolism in Ascaris muscle have been investigated in comparison with those of hexylresorcinol (Hex), santonin (S) and piperazine (Pip). (1) Hex (200 approximately 400 mug/ml) showed a strong nonspecific inhibition on the formation of succinate from fumarate in muscle homogenate, the phosphofructokinase (PFK) activity in cytoplasm, and the electron transfer activity in mitochondria. (2) S(100 approximately 400 mug/ml) and Pip (100 approximately 400 mug/ml) were inneffective on these activities. (3) IT inhibited the formation of succinate from glucose and fumarate in muscle homogenate (100 approximately 400 mug/ml), the PFK activity in cytoplasm (400 mug/ml), and the mitochondrial succinate oxidase system (25 approximately 400 mug/ml). These results suggest that IT elicits the wormcidal action by inhibiting the energy metabolism of Ascaris muscle mitochondria.


[Relationship between biogenic amines and analgesic action of difenamizole in heat induced reflexes].

Effects of drugs that modify catecholaminergic or tryptaminergic mechanisms were determined in experimental animals regarding the analgesic action of difenamizole, morphine, and aminopyrine. Analgesia was assessed by the hot plate method in mice and the hot water induced tail withdrawal reflex in rats. Both 5-hydroxytryptophan (5-HTP) and L-dopa potentiated the analgesic action of morphine, but antagonized the action of difenamizole in the hot plate test. p-Chlorophenylalanine (pCPA), alpha-methyl-p-tyrosine (alpha-MT), and reserpine antagonized the effect of morphine as assessed by this same test. alpha-MT potentiated the analgesic action of difenamizole. The analgesic action of aminopyrine was hardly modified in the hot plate method by pretreatment with 5-HTP, pCPA, L-dopa, and alpha-MT. In rats, 5-HTP antagonized the effect of morphine, while pCPA, L-dopa, and alpha-MT caused no appreciable change in the analgesic action of morphine in the hot water induced tail withdrawal reflex. The effect of difenamizole was not modified by pretreatment with these monoamine-related drugs. On the other hand, brain 5-hydroxytryptamine content was increased by pretreatment with 5-HTP in both tests. These results suggest that the analgesic action of difenamizole and morphine, as measured in the hot plate test in mice, may be mediated by catecholamines and 5-hydroxytryptamine, but that other mechanisms may be involved in the hot water induced tail withdrawal relfex in rats. In addition, the biogenic amines may play a different role depending on the type of analgesic.


A study of psychomotor epilepsy with "kindled" cat preparations.

Seizure development was examined in amygdaloid (AM), hippocampal (HIPP) and septal (SEPT) "KINDLED" CATS BY  BEHAVIORAL AND Electrographic methods. hipp seizure developed into motor seizure after establishing secondary epileptogenesis in AM and globys paliidus. A secondary epileptogenesis in the hippocampus was not necessary for AM seizures to develop into generalized conculsions. The SEPT seizure development was almost identical to the hippocampal seizure development. This latter finding suggests that psychomotor epilepsy may not only ne triggered by the HIPP and AM focus but by the septum and its related structures. In the second experiment, the effect of various neuroactive agents on the interictal dischage frequency was studied in AM and HIPP kindled cats. Clear antagonistic action of L-Dopa against reserpine or alpha-MPT induced increase of IID frequency was observed. Viewed in conjunction with our previous assay study of catecholamine that showed a marked depletion of both norepinephrine and dopamine, in hippocampal kindled cat brain, it can be concluded that catecholamine inhibits the establishment and activation of the kindled epileptic neurocircuits.


Current angiographic approach to diagnosis and therapy of acute gastrointestinal bleeding.

The author's current angiographic approach to the diagnosis and therapy of acute gastrointestinal (GI) bleeding is summarized and discussed. It is based on the authors' experience with diagnostic studies in more than 300 acute GI bleeders and the use of various angiotherapeutic techniques in 138 of them as well as the experience of others. A "moderately aggressive angiographic approach" is advocated for the diagnosis of acute GI bleeding in most patients with angiography used as needed after emergency endoscopy and preliminary medical therapy. Vasoconstrictive angiotherapy with selective intraarterial use of vasopressin is partially giving way to low dose, intravenous infusion of vasopressin and, where possible, to direct vascular occlusion. Selective transcatheter embolic occlusion of bleeding vessels is in indicated cases an accepted method for controlling arterial bleeding. Medical gelatin (Gelfoam) is the current authors' embolization material of choice. Selective variceal occlusion offers promising means for management of bleeding from gastroesophageal varices. Its possible combination with transcatheter intrahepatic portosystemic shunting might also provide non-surgical relief of portal hypertension.


[Interpretation of the x-ray signs of osteoporosis as special aspect of the new haemodynamic biostatic theory of osteoporosis (author's transl)].

Based on the author's new haemodynamic biostatic theory of osteoporosis the typical symptoms of osteoporosis are demonstrated by X-ray, revised, interpreted and completed. Atrophy of trabeculae related to osteoporosis, consequences for vertebrae bodies and vertebrae column are chronologically explained. Introduction and distribution of force are discussed and the special importance of muscular system and discs to maintain supporting capacity is emphasized.


[Measurements of bone mineral concentration ("hydroxylapatite-volume values") and of bone density in vitro and in vivo with a densitometric method using beams of two different energies (author's transl)].

The densitometric method of Rassow-Strüter (1969) using beams of two energies permits separate estimations of bone mineral and connective tissue concentrations in bone; their sum indicates bone density. The value of the method has been examined and the early results of in-vitro and in-vivo measurements are quoted. The former were obtained from pairs of macerated calcanei and vertebral bodies embedded in resin blocks. The in-vivo estimations were concerned with obtaining normal values in healthy children aged four to fifteen years and adults aged 18 to 54 years. Standard deviation, obtained from measurements of four different points of both calcanei in adults was KM 12% for Hydroxylapatite-volume values, and for bone density 14%. The average value for KM for the whole group is 198 mg/cm3 with 17% standard deviation of the single measurements compared with the average. The following-up measurements for children with renal disease do not yet allow final conclusions about the correlation of the clinical aspects of case to the measured bone parameters and their value as independent criteria. For 16 nursing mothers a significantly lower average HA volume value KM = 149 mg/cm3 +/- 21% was found.


[Pulmonary vessel calibre on in- and expiratory chest radiographs in young and old normal people (author's transl)].

Changes in pulmonary blood flow as see on chest radiographs have assumed considerable importance recently in the evaluation of left ventricular insufficiency. In order to study the results of poor radiographs on the evaluation of pulmonary haemodynamics, blood-flow patterns were studied in 39 individuals of various ages during normal inspiration, during the Valsalva manoeuvre and during expiration. All had normal lungs. The results indicate that changes in blood-flow patterns and loss of marginal definition of basal vessels are unreliable signs of left-sided insufficiency in old patients or in unco-operative patients, in the presence of a high diaphragm and in the supine position.


[Large solitary aneurysm of the left coronary artery. Plain films and angiography (author's transl)].

The diagnosis of coronary aneurysms has for a long time been made at autopsy. After a general review of coronary artery aneurysms, a large aneurysm of the circumflex branch of the left coronary is described; this was diagnosed by selective coronary angiography and successfully treated by surgery. The results are compared with six other reported cases of pre-operatively diagnosed coronary artery aneurysms. Since complications, such as rupture, embolisation or infarction, are common in large coronary aneurysms, early diagnosis is desirable. An abnormal bulge of the cardiac contour or circular calcification within or at the edge of the cardiac shadow may be suggestive of the diagnosis.


[Confluent pulmonary deposits from carcinoma of the breast under cytostatic therapy (author's transl)].

Cases of disintegrating pulmonary metastases are presented. Most interesting are cavitations which occur under cytostatic therapy. An increasing number of cavitous metastases might be seen under propagated cytostatic therapy.