Separation of human lymphoid cells by preparative cell electrophoresis.

By means of free-flow electrophoresis a preparative separation of cells according to their surface charge is achieved. The method has been applied to human lymphocytes of blood and of tonsils. Technical details are described and discussed with respect to optimal separation conditions, reproducibility of results and viability of the separated cells. Unseparated cells, pooled separated cells and cells corresponding to different electrophoretic mobilities are compared for stimulation in response to PHA, determination of cells bearing membrane immunoglobulins, colony growth of hemopoietic stem cells and DNA syntheses in vitro. It is concluded that reproducible results can be obtained, that the biological activities of the cells after separation are unaltered and that a separation or at least an enrichment of cells with certain properties can be achieved.


The cytotoxic activity of mouse T lymphocytes against allogeneic cytotoxic T cells.

Using a 51Cr cytotoxicity assay, the sensitivity of murine cytotoxic T cells to T cell mediated cytotoxicity has been tested. Two experimental approaches have been used. First, cytotoxic T-blast-lymphocytes (CTBL), enriched by the velocity sedimentation at 1 g were used both as cytotoxic effector cells and as 51Cr-labelled target cells. It was found that murine CTBL are capable to lyse directly and specifically allogeneic CTBL within 200 minutes. The second approach used was to incubate CTBL together with CTBL, the cytotoxic activity of which was directed against the transplantation antigens of the added allogeneic CTBL population. After 10 hours, the residual cytotoxic activity was tested. Again it was found that CTBL were capable of functionally inactivating allogeneic CTBL. Therefore the results obtained are incompatible with the concept that target cell lysis by cytotoxic T lymphocytes is mediated by a non specific "lymphotoxin", secreted by activated T cells after the antigen-recognition phase in the confined space between T cells and target cells.


Gilbert's syndrome and HL-A. Preliminary report.

HL-A antigens were determined in 18 unrelated patients with Gilbert's syndrome and 3 families where this condition occurred in 2 generations. The data obtained do not point out an association between HL-A antigens and Gilbert's syndrome.


[Histocompatibility-antigens in hay fever (author's transl)].

HL-A antigens have been determined in 110 not related Caucasian patients from southwest Germany suffering from hay fever and in 353 blood donors from the same area. Gene-frequencies and haplotype-frequencies of these 2 groups were compared, deviations within various specific allergy groups were investigated taking into consideration associated diseases. Patients suffering from hay fever showed a significant increase in frequency of W 19 and a significant decrease in HL-A8. Increase of W 19 was most evident in persons who became sick before the 16th year of age and in those who showed asthmatic symptoms in addition to those of hay fever. HL-A8 is significantly decreased only in persons who became sick after the 16th year of age. Found differences in haplotype-frequencies need further confirmation in larger studies. A relationship between changes of HL-A frequencies in hay fever due to special pollen allergies could not be determined.


Biologic activity of soluble collagen-anticollagen immune complexes as demonstrated by passive cutaneous anaphylaxis.

Collagen-anticollagen immune complexes were prepared by gel filtration. Complex formation was chemically and serologically demonstrated. Complexes eluting in gammaM- and gammaG-peaks of antigen-antiserum mixture showed strong positive reactions in PCA experiments performed with 20 guinea pigs. Control preparations of gammaM- and gammaG-peaks of antiserum devoid of antigen gave significantly lower PCA-response. The positive reaction of control preparations can be explained in part by a certain degree of cross-reactivity of anticollagen-antibodies with guinea pig collagen.


[The typing of group A haemolytic streptococci. V. Communication: type differentiation within the T-complexes 3, 13, B3264 by means of monospecific T-antisera (author's transl)].

Monospecifically reacting T-antisera can be prepared by the absorption technique of Takizawa, Akiyama and Miyamoto for the Streptococcus pyogenes types 3, 13, B3264 and by conventional techniques for the types 41 and 56. The findings were confirmed by correlation of the T-type with the M-type. This method to a large extent enables typing of group A-streptococcal strains with the T-complex 3, 13, B3264. M-precipitation allows this to a far lesser degree, since M-antigens are produced by only a fairly small percentage of these types. Approximately 90 percent of the 1132 strains agglutinating with T 3, 13, B3264-complex antiserum could be assigned to one of these 3 types by use of monospecifically reacting T-antisera. The epidemiological analysis is considerably improved by this system. The results of the T-typing are in agreement with the outcome of the serum opacity reaction (SOR). Strains belonging to types 3, 41 and 56 react negatively in the SOR, strains of type 13 and B3264 show a positive SOR. The types 33, 43, 52 and 53 possess an identical T-antigen, so that monospecifically reacting T-antisera could not be prepared for these types.


Clinical trial of Ro 6-0787, a monovalent specific hapten inhibitor of penicillin allergy.

A second clinical trial of the compound Ro 6-0787, which is a specific monovalent penicilloyl hapten inhibitor of allergic reactions to penicillin has been conducted by investigators from 9 different European groups in 90 patients allergic to penicillin. The effect of a combined Ro 6-0787-penicillin therapy was considered as clinically successful in the large majority of cases, since treatment with penicillin could be pursued or resumed without allergic manifestation in 42 from 46 cases (91 percent). The effect of Ro 6-0787 alone on acute allergic manifestations after interruption of penicillin therapy was more difficult to evaluate but was nevertheless considered satisfactory in 17 from 26 patients (65 percent). A depression of skin hypersensitivity to PPL and/or penicillin and penicillin derivatives sometimes persisting for weeks and months was obvious in numerous allergic patients submitted to combined Ro 6-0787-penicillin treatment. A depressing effect on antipenicillin antibody titers detected by passive hemaglutination was also manifest in some patients. Failure to suppress allergic manifestations was reported in 11 cases, among which some may have been due to insufficient dosage of inhibiting hapten. The overall tolerance of Ro 6-0787 in allergic patients has been very good. Nevertheless, the major obstacle to a wider general use of Ro 6-0787 at the present time appears to be the occurrence of positive skin reactions to that compound in approximately 5 percent of patients allergic to penicillin. It is not yet ascertained whether the occasional positive skin reactions and urticaria to Ro 6-0787 may have been due to aggregation, or incomplete dissolution of the compound or whether it reflects hypersensitivity to another antigenic determinant. With the reservation that patients with positive skin test to Ro 6-0787 have for the time being to be excluded from combined treatment, this monovalent hapten certainly offers a new possibility to resume and/or pursue penicillin therapy in patients demonstrably allergic to that drug.


[Proteinase-inhibitors and enzyme-active proteins from fish eggs. Fibrinagarelectrophoretic and immunoelectrophoretic studies (author's transl)].

Saline extracts from eggs and homogenized spermaplasma from 2 fresh water fishes and 2 sea-fishes were investigated using fibrin-agar-electrophoresis and the immunoelectrophoretic analysis. Many polyvalent proteinase-inhibitors with different inhibition spectra, lipoproteins and esterase active proteins which split beta-naphthylacetate as substrate were detected and designated according to a proposed nomenclature. Fresh water fishes contained more inhibitors than sea-fishes. The proteinase-inhibitor PI-Sg3 antigen-antibody complex was esterase active; the active complex designated PI-Sg4 could not yet be exactly coordinated in respect to another proteinase-inhibitor from Salmo gairdneri. The separation of pseudo- and euglobuline fractions permitted a significant concentration of proteinase-inhibitors and the elimination of large parts of strong antigenic proteins. A good antiserum could be prepared which showed 3-5 precipitation lines against proteinase-inhibitors from trout eggs. By means of cross reactions it could be demonstrated the nonspecificity of several proteins in respect to species, genus and sex. This concernes also some aspects of immunesera absorptions with heterologous protein mixtures. Cross reactions with proteinase-inhibitors couldn't be detected, suggesting that they are genus-specific. This is also confirmed by their variable number and inhibition-spectra in extracts of different origin.


[Pathogenesis of neural lesions in Marek's disease. I. Allergic skin reaction against myelin of the peripheral nerves (author's transl)].

23 chickens affected with Marek's disease were tested by the allergic skin reaction for delayed hypersensitivity against myelin and myelin preparations of peripheral nerves. 19 animals proofed to be positive in the skin test, yet there was no correlation with the intensity of the nerve affections. 4 animals with severe mononuclear neural infiltrations didn't show any allergic skin reaction. It could be demonstrated that in Marek's disease lymphocytes are sensitized against components of the peripheral myelin. Thereafter, Marek's disease stands in analogy to the Guillain-Barré syndrome of man, as well as to experimental allergic neuritis.


[Immunglobulin G-, M- and A-levels after 3 and 6 days intravenous treatment by D-penicillamin (author's transl)].

In 10 patients with lung fibrosis the serum levels of immunglobulins G, A and M were determined before and after a 3 days-treatment by D-Penicillamine (1.0 g/die i.v.) by the radialimmunodiffusion method of Mancini. There is a fall in the immunglobulins IgG and IgM, the levels of IgA are not lowered. Continuing the treatment with 2 times 1.00 g D-Penicillamine per day for 3 further days does not lower the levels of IgM and IgG further.


[Examinations of the behaviour of immunoglobulins IgG, IgA, IgM in comparison to the immunoserological reactions in human chronic brucellosis (author's transl)].

The authors determined the levels of the immunoglobulins IgG, IgA and IgM in the serum of 70 patients with chronical brucellosis which was diagnosed on the basis of epidemiological, clinical and laboratory examinations. The Ig-levels were compared with immunoserological reactions of brucellosis as Wright, Coombs, Burnet, complement fixation tests. A significant increase of immunoglobulin G without a positive correlation with the values of immunoserological reactions was found.


[Change of the prevalent subtype of hepatitis B antigen in acute hepatitis B infections (author's transl)].

Subtyping of hepatitis B antigen (HBs Ag) in patients with acute hepatitis B revealed subtype ay in 75 percent while subtype ad was much more common in chronic hepatitis B infections: 81 percent of HBs Ag positive blood donors and 76 percent of patients with HBs Ag positive chronic aggressive hepatitis revealed subtype ad. In contrast to blood donors and chronic hepatitis patients, a change of the prevalent subtype was noted in acute hepatitis patients between 1970 and 1974. Before May 1972, subtype ad was found in 67 percent of patients, whereas later subtype ay dominated in 93 percent. An unequal distribution of subtypes between acute and chronic forms of hepatitis B infections has been explained by differences in the virulence of virus strains. Our results suggest that the higher prevalence of subtype ad in longterm carriers may be due to infection during an earlier time when subtype ad was also common in acute infections. The change of the prevalent subtype in acute infections may be attributed to differences in contagiosity rather than differences in virulence of virus strains.


[The importance of phosphatidylcholine in the binding of anti-D to human erythrocyte ghost membrane (author's transl)].

Incubation of Rh positive ghosts with phospholipase A2 and C abolished the adsorption of Rh antibodies on the ghosts; incubation with phospholipase D, however, did not affect their adsorption and none of these phospholipases affected the adsorption of antibodies of the ABO system. The impairment of antigen-antibody-reaction in Rh positive ghosts treated with phospholipase corresponds to the absence of the antigen-antibody reaction with the membrane protein associated with Rh characteristics in the Schultz-Dale-Test. The chromatogram of the phospholipids extracted from those stromata treated with various phospholipases and those not treated showed different patterns. After incubation with phospholipase-A2 the lecithin and cephalin streaks were reduced and in addition lysophosphatide and fatty acid streaks were detected. In the case of phospholipase C the lecithin and cephalin streaks were further reduced while diglyceride streaks made their appearance. The phospholipid extracts from those stromata treated with phospholipase D and those not treated were identical. Phospholipase C reduced the values of lipid phosphorus more than did phospholipase A2, while phospholipase D did not reduce them at all. This study supports the results of other investigators who have postulated that the Rh antigens are located in a lipoprotein on the membrane of the human erythrocyte. The antigen-antibody-reaction seems to require a precise protein-phospholipid interaction.


The serum immunoglobulin levels in Down's syndrome and other diseases associated with mental disorder.

The serum levels of IgA, IgM, IgG and IgD were determined in patients with Down's syndrome (69 cases), Oligophrenia (101 cases) and Morbus Wilson (18 cases). In sera from Down's syndrome patients a significant increase in the levels of IgA, IgG and IgD were found. IgM levels were identical to those of healthy controls. The immunoglobulin levels in both the oligophrenia and Wilson's disease patients were not different from those of controls.


[The influence of experimental diabetes on the distribution of LDH-isoenzymes in rat skeletal muscle (author's transl)].

The distribution of LDH-isoenzymes from homogenate-supernatant of M. soleus of normal and streptozotocin-diabetic male rats was investigated by agargel-electrophoresis. Five LDH-isoenzymes could be detected in the M. soleus of normal rats; the average proportion of H-subunits was 69.1% (age 3-4 month) resp. 69.6% (age 13 month) from the total value. In male rats of the same age a mild diabetes was induced by intravenous injection of 65 mg streptozotocin per kg body weight. In the M. soleus of these animals also 5 LDH-isoenzymes were detected. After 1-2 month duration of diabetes the LDH1 is decreased from 30.3% of controls to 18.2% and the LDH4 is increased from 11.1% of controls to 20.1%. The H-subunit value decreased to 61.9% from the total value. In long term diabetes (11 month) the values of single fractions and the H-subunit value did not differ from those of controls. The findings are discussed considering the composition of M. soleus on different fiber types and the influence of diabetic conditions.


[Experimental foreign serum pancreatitis. Histologic and histochemical findings in the exocrine pancreas of the mouse after repeated intraperitoneal injections of serum of other species (author's transl)].

Adult white mice were continually treated by intraperitoneal injections of normal serum of various species (neat, horse, man, rabbit, mouse) for 3 hours up to 16 days. Control animals received injections of physiological saline under the same conditions. In the mouse pancreas, the repeated intraperitoneal injections of foreign serum conformably resulted in an interstitial edema, a first granulocytic and histiocytic, later on markedly lymphoplasmactyic interstitial inflammation with single dystrophic acinar cells as well as in a mild intersitial fibrosis after 8 or 16, resp., days of serum application. Histochemically, the exocrine pancreas cells showed a moderate increase in activity of adenosintriphosphatase, nonspecif esterase as well as acid and acaline phosphatase. All the changes described were most considerably pronounced after treatment with bovine serum. The interstitial pancreatitis after continual foreign serum applications regarded as the morphologie expression of a pathogenic immune phenomenon of the serum sickness type in case of a serum sickness reaction taking place preferably in the peritoneal cavity.


[Relationship between morphometric placental studies and clinical biochemical findings in EPH-gestosis].

The relative fetal vascular surface established morphometrically in 22 gestosis placentas was clearly decreased compared to normal placentas. An accordance between the result of the DHEA-S-tolerance test and the relative fetal vascular surface was demonstrable in parts only. On the other hand, we, too, are able to confirm the results described in the literature that the restrictions of the fetal vascular surface correlate with the increase of the gestosis index.


[Experiences with the dehydroepiandrosterone sulfate test at the end of pregnancy].

Results of DHAS-tests are calculated according to 4 methods (recovery of injected DHAS as total oestrogens measured in 24 hour urine specimens; changes of oestrogen excretion peaks measured in two hour intervals; recovery of injected DHAS as total oestrogens measured in 2 hour urine specimens; classification according to a scheme of oestrogen excretion pattern measured in two hour intervals). The results are critically compared with the general development of pregnancy and with the condition of the newborn. The discrepancies observed show that the DHAS-test is of little practical value.


Identification of the ouabain-binding peptide of (nak)-atpase).

The [3H]-ouabain-(NaK)-ATPase complex when treated in the cold with sodium dodecyl sulfate (SDS) dissociates into a larger and smaller peptide called alpha and beta, resp.. Analysis of the released peptides by SDS-polyacrylamide gel electrophoresis reveals that [3H]-ouabain co-migrates with the alpha-peptide only, being apparently identic with the ouabain receptor molecule. The percentage occupancy of the receptor peptide with [3H]-ouabain can be increased up to 90% evidencing the stabilization of the [3H]-ouabain-alpha-peptide complex by SDS-exposure and release from the oligomeric enzyme. A hypothetic explanation for the seemingly paradoxical stabilising effect of SDS on the complex is offered.


Reaction of yeast phosphofructokinase with succinic and maleic anhydride.

Modification of yeast phosphofructokinase by succinic and maleic anhydride influences the catalytic activity and the allosteric behaviour of the enzyme. Depending on the degree of succinylation and maleinylation a decrease of maximum activity, an increase of the apparent affinity for fructose-6-phosphate, a decrease of the Hill-coefficient and a diminution of ATP-inhibition are observed. Up to about 40% of the lysyl residues could be succinylated without dissociation of the hexameric protein, however with a decrease of the enzyme activity. More extensive succinylation or maleinylation causes a dissociation into subunits. The sedimentation coefficient is lowered from 20 S to about 3 S. The molecular weight of the smallest dissociation product was determined to 50 000 (+/- 10 000) by the sedimentation equilibrium method. The number of bound succinyl groups, as determined from radioactivity incorporation, exceeds the content of lysyl groups of the enzyme, indicating that the modifying reagent is also reacting with other amino acid residues.


Femoropopliteal and femorotibial arterial reconstructive surgery. Special reference to the autogenous venous bypass procedure using unreversed vein after eversion valvectomy.

The outcome of 127 femoropopliteal and 23 femorotibial arterial reconstructions carried out between January 1960 and December 1972 has been reviewed. The operative method was autogenous saphenous vein bypass in 109 cases, 82 of which were performed using unreversed vein with eversion valvectomy. The indication for reconstruction was advanced ischemia in 39%. Two patients died primarily and 23 late deaths have occurred subsequently. 19 grafts or reconstructed segments became occluded primarily. Most of them were femorotibial reconstructions of Dacron bypass reconstructions. Most of the failures occurred within 1 year of surgery. Using eversion valvectomy technique, the 1- and 5-year patency rates were 57 and 50% respectively. In femorotibial reconstructions the 1-year patency rate was 36%. There was a distinct difference in patency between the cases with excellent of good outflow and those with fiar or poor outflow. The difference was less distinct between patients with claudication and those with advanced ischemia. Eight limbs needed major amputation.


Electromagnetic measurement of the arterial blood flow in the femoropopliteal region.

To determine the blood flow in healthy femoral arteries electromagnetic measurements were made on common femoral, superficial femoral and profunda femoris artery in 20 patients during operation for varicose veins. The values obtained were 239 ml/min, 134 ml/min, and 104 ml/min respectively. These registrations were compared with those achieved during reconstructive arterial surgery. It was found that the average basal flow values from corresponding arteries were rather similar. The flow values registered from femoropopliteal bypass grafts were identical with the flow values from the superficial femoral artery of varicose patients. The papaverine response of the common femoral artery flow was tested in 7 varicose patients. The average increase was 250%. None of the average responses from various arteries during arterial reconstructive surgery reached this value. The papaverine responses in femoropopliteal bypass grafts were closely correlated with the arteriographically estimated outflow potential. The flow values both at rest and during vasodilatation showed a great range in all vessels measured.


[Cyproterone acetate - ethinylestradiol treatment of hirsutism, acne, seborrhea and alopecia].

Twenty-five female patients, aged 14 to 49, and suffering from syptoms of virilization (hirsutism, acne, seborrhea and alopecia) were treated with an estrogen-progestogen combinantion, i.e. cyproterone acetate and ethinylestradiol, having antiandrogenic and antiovulatory action. Patients were submitted to monitoring by means of a series of laboratory tests in order to detect any toxic or hormonal effects that might occur. In most cases symptoms of virilization were significantly reduced, while untoward side effects were not noted.


Histochemical studies of pedicellaria of an echinoid, Salmacis bicolor.

The tridentate pedicellaria of Salmacis bicolor consists of calcareous head and stalk, connected by a muscular neck regions. Head, neck and stalk are covered by a thin cuticle, which is non-mineralized and soft. Both the cuticle and the organic fraction of the calcareous region are resistant to acids and alkalis. Histochemical studies reveal that both the cuticle and the organic matrix of the calcified head and stalk contain protein, polysaccharide and lipids. The lipid content of the organic fraction of the mineralized matrix recalls the spicules of Pluteus larva reported in an earlier study. The protein component of the cuticle and that of the organic matrix slightly differ in that the former is rich in aromatic amino acids, namely tyrosine and tryptophane. Both cuticle protein and the protein of the organic matrix lack sulphur containing aminoacids. Another feature of similarity between the cuticle and the organic matrix is that both contain acid mucopolysaccharide and neutral mucopolysaccharide components. The role of acid mucopolysaccharide in calcification is discussed. The neutral mucopolysaccharide has been suggested to be similar to chitin, and its significance is discussed. Unlike the skeletal elements of other invertebrates, the cuticle and the organic matrix of pedicellariae are devoid of any phenolic compounds.


Histochemical studies in stomatal apparatus of Phaseolus mungo Linn. I. Localization of enzymes and structural material.

In the present investigations, the localization of several enzymes (Acid Phosphatase, Peroxidase, succinic dehydrogenase, Phosphorylase, alkaline phosphatase, ATP-ase) and other substances in the guard and subsidiary cells as well as trichomes of the leaves of Phaseolus mungo, was carried out. Attempts were also made to follow the sequence of developmental stages starting with meristemoids and culminating in differentiated structures. The basic information thus obtained is used in interpreting the developmental physiology of stomatal differentiation as well as their cellular organisation. Histochemical observations made in the present studies are compared with the electron microscopical observations of Whatley (1972). It is proposed that mitochondria played a basic role in the functioning of the guard cells. The present studies also demonstrated activity of acid phosphatase in the guard cells and was localized in spherosomes. The latter varied in the activity for acid phosphatase and was dependent on the turgid level of the cell. Interestingly, enough localization of phosphatase could only be observed in spherosomes when the osmotic pressure in the cell was relatively low, once the osmotic pressure increased, the activity disappeared.


Histochemical studies in stomatal apparatus of Phaseolus mungo linn. IV. Mechanism of stomatal action.

The histochemical studies were carried out in the open and closed stomata of Phaseolus mungo leaves. Several enzymes like, Acid phospatase peroxidase, succinic dehydrogenase, phosphorylase, alkaline phosphatase, ATP-ase etc. were localized in the guard and subsidiary cells of epidermal peel. On the basis of cytochemical localization, enzyme activity was precisely interpreted. In the light of fluctuations in the localization, activities of different enzymes, an attempt is made to provide the functional interpretation of stomatal mechanism. We have attempted to correlat our observations in relation to diurnal metabolisms. Our studies suggest that starch-sugar inter-changes played a vital role in the stomatal regulation. We are also inclined to believe that besides guard cells, subsidiary cells also influenced the turgid conditions. A model based on available facts in collaboration with our own studies is presented which tends to explain the stomatal regulation.


A cytochemical study of the "chloride cells" in the skin of a fresh-water teleost (Channa striata (Bl.) Channidae, Pisces).

The chloride cells in the skin of Channa striata have been described. The cytoplasm of these cells is filled with acidophilic, osmiophilic and sudanophilic granules. The sudanophila is due to phospholipids. These cells give positive reaction for chloride ions and exhibit the presence of neutral mucopolysaccharides. The cytoplasm of these cells is packed with numerous mitochondria and exhibit high succinic dehydrogenase activity which may provide the energy needed for the active transportation of ions. Alkaline phosphatase activity could not be demonstrated in these cells. The presence of chloride cells in comparatively large numbers in the regions where the epidermis is thin is correlated as an adaptation for the increased efficiency of these cells for the transportation of ions so as to maintain the osmotic concentration of its body fluid which is higher than that of the surrounding medium.


Nutrition effect on liver and lysosomes. VIII. The undernourishment role in a following short-term starvation.

91 male, albino rats, Wistar strain, with body weight 150 +/- 10 g, subdivided into 2 series were investigated. The 1rst series animals (E) were fed on single daily meals in the course of 20 days, only 2 h in 24 h and after that period were subjected to complete starvation and investigated on the 24th, 48th, 72th and 96th h resp. after the ceasing of food supply. A 2nd animal series (C) serves as a control, which in the course of 20 days, were on a all-round diet and later put in identical conditions of complete starvation and also investigated on the 24th, 48th, 72th and 96th h. The liver histological, histo-enzymatical (AP, BG, AlkP and ATP) and electron microscopic changes followed up, as well as certain physiological, biochemical and morphometric indices. The dynamics of the alterations in complete starvation and the confrontation of the data between the 2 animal series with different preceding nutritional regimes show that: 1) single daily meals leads to real undernourishment; 2) the undernourishment predetermines a more severe course of the following period of complete starvation; 3) 3 phases are established during the complete starvation: adaptive, alterative-restorative and alterative. Each phase bears a definite subcellular characteristics where the lysosomes apparatus plays an essential role.


Histochemical localization of adenosine triphosphatase and thiamine pyrophosphatase in the digestive system of a teleost fish, Ophiocephalus punctatus.

The localization of ATPase and thiamine pyrophosphatase in the digestive system of Ophiocephalus punctatus has been studied. In stomach ATPase is found in the free border of the mucosa, gastric glands, submucosal connective tissue nuclei and muscularis. Thiamine pyrophosphatase is localized only in the mucosa and gastric gland cells. In the intestine, pyloric caeca and rectum, ATPase is distributed along the brush border of the columnar epithelial cells, their nuclei and cytoplasm. Mild activity is also found in the nuclei of submucosa and muscularis. The activity is stronger in the intestine than in the other portions. Thiamine pyrophosphatase activity in these portions is restircted only to the goblet cells. In the liver ATPase activity is associated both with the cytoplasm and nucleus of the hepatic cells. Thiamine pyrophosphatase activity is maximum in the centro-lobular portion.


Postnatal study on the histochemistry of epididymis in buffalo (Bubalus bubalis).

The histochemical localisation and development of carbohydrates, acid mucopolysaccharides, lipids and desoxyribonucleic acid has been determined in the head, body and tail segments of buffalo epididymis at different stages of postnatal development from 3-76 weeks of age. The cytoplasm contains numerous Schiff-positive, diastase-resistant granules which are abundant in the apical region of the epithelial cells at 3-52 weeks. They decrease in number at 72-76 weeks and instead, a diffuse Schiff-positive material is observed in the cytoplasm of the cells, particularly in regions III-VI of the epididymis. In all the stages of development, the basement membrane and the luminal border of the epithelial cells have strong PAS-positive reaction. The intertubular connective tissue is mildly PAS-reactive, with moderate activity on the endothelial lining and smooth muscles of blood vessels. The capsule shows an intense Schiff-positive material in the fibers while the stereocilia are mildly reactive. PAS activity is less in region I and greater in regions V-VI as compared with the other regions of the epididymis. A moderate quantity of lipids is present in the epithelial cells and smooth muscles of the tubules. Sudanophilia is more pronounced in the tail region as compared with the head and body regions of the epididymis. Acid mucopolysaccharides are present, minutely, in the epithelial cell cytoplasm, with moderate activity on the stereocilia of the tubules. The Feulgen reaction is deep in region I and light to moderate in the other regions of the epididymis.


Malignant hyperthermia in a family. The neurophysiological and light microscopical study of muscle biopsies of healthy members.

12 healthy persons--close relatives to two children who died of malignant hyperthermia--volunteered for biopsies of striated muscle and skin, electromyography and electroencephalography. The investigations of muscle biopsies comprised material for enzyme histochemistry and ordinary light microscopy including visualization of the intramuscular nerves. Out of 12 clinically healthy persons 9 revealed abnormalities of the muscle fibres, 11 showed degenerative and regenerative alterations in the intramuscular nerves, in EMG 7 turned out to produce slight neuropathy, and 7 displayed abnormal EEG tracings. These findings support the idea that the etiological key (or keys) in the peculiar pathophysiological entity of malignant hyperthermia may even be found outside the striated muscle cell.


Effects of hypoxia of 10-45 seconds duration on energy metabolism in the cerebral cortex of unanesthetized and anesthetized rats.

Glycolytic and citric acid cycle intermediates, as well as organic phosphates, were measured in the cerebral cortex of unanesthetized rats following arterial hypoxia (administration of 6-8% O2) of 10 and 20 s duration. There were decreases in glucose-6-phosphate and fructose-6-phosphate, and increases in fructose-1,6-diphosphate, dihydroxyacetone phosphate and 3-phosphoglycerate, even before pyruvate accumulated. Since measurements of the lactate concentration showed that there was an increased glycolytic rate, the results demonstrate that phosphofructokinase was activated. The glycolytic changes were accompanied by, and probably due to, minor changes in phosphocreatine, ATP, ADP and AMP. Experiments of anesthetized animals showed that hypoxia for 45 s was accompanied by signs of phosphofructokinase activation, even if tissue PCO2 was kept constant. It is concluded that, irrespective of the tissue CO2 tension, hypoxia is accompanied by activation of phosphofructokinase which, at least initially, is responsible for the increased glycolytic rate.


A study on the nuclear extrusion of mammalian erythroblast.

A study was carried out to clarify the mechanism of nuclear extrusion of mammalian erythroid cells by observing erythroblasts of rabbit under various conditions in vitro. The animals were made anemic by phenylhydrazine injection and erythroblasts were obtained from the peripheral blood and observed morphologically after a certain time of incubation. After two hour incubation at 37 degrees C, about 50% of erythroblasts were denucleated. The nuclear extrusion was remarkably suppressed by the inhibitor for electron transport system or by uncouplers for oxidative phosphorylation. It was also arrested by the inhibitor of cell movement, like cytochalasin B. In contrast, monoiodo-acetic acid, ouabain and colchicine hardly inhibited the nuclear extrusion. The observations indicated that the nuclear extrusion of mammalian erythroblast is an energy-dependent process in connection with the function of contractile microfilamentous system susceptible to cytochalasin B.


Energy dependency on the salt-resistance of Staphylococcus aureus: Effects of various inhibitors on the growth in high salinity condition.

It has previously been shown that the barrier system for high environmental salinity is closely related to the salt-resistance of Staphyloccus aureus. The present investigation was undertaken to clarify the energy dependency for the maintenance of intracellular univalent cation contents in cells grown on high concentration of salt containing medium. The results are summarized as follows: (1) The growth of 10% NaCl-Staph which was grown in the 10% NaCl containing nutrient broth was more sensitive to NaN3 than Normal-Staph which was grown only on nutrient broth. The anaerobic conditions in both media demonstrated a more powerful effect on growth inhibition of 10% NaCl-Staph than Normal-Staph. Therefore, 10% NaCl-Staph must have a higher energy dependency than Normal-Staph. (2) The high sensitivity to uncouplers, such as DNP and FCCP in 10% NaCl-Staph, also suggested an energy dependency which was probably related to respiration and not to anaerobic glycolysis. (3) The intracellular Na+ contents of Normal-Staph and 10% NaCl-Staph were 12.0 and 152.9 mmoles per Kg wet weight of cells respectively, and the content of K+ in 10% NaCl-Staph (90.2 mmoles per Kg wet weight) was lower than that of Normal-Staph (215.8 mmoles per Kg wet weight). These intracellular Na+ and K+ contents were strongly affected by the addition of various inhibitors to the medium. The measurements of intracellular univalent cation contents indicated the existance of an adaptively developed barrier system in 10% NaCl-Staph and the existence of energy-dependent transport mechanisms for efflux of Na+ in Normal-Staph and for the influx of K+ in 10% NaCl-Staph.


Allogeneic inhibitory activity of regional lymph node cells in the mouse isografted with methylcholanthrene-induced tumor.

In mouse bearing progressive cancer a decrease was present in the allogeneic inhibitory activity of T-lymphocytes, which constitutes the core of immunological surveillance system in mammalians. For tests, methylcholanthrene-induced tumor (MC-tumor) was isografted subcutaneously on the back between scapulae of C3H mice, and the lymphocytes were prepared from the regional axillary lymph nodes removed from these mice at 1, 2, 3, or 4 weeks after grafting. These lymph nodes cells were cultured together with 40-fold numbers of allogeneic JTC-11 cells derived from Ehrlich cancer cells in a culture medium containing 2.0% (v/v) PHA for 24 or 48 hours. The proliferation rate of JTC-11 cells (increased numbers) at weekly interval was considered the allogeneic inhibitory activity of lymph node cells. As a result it was demonstrated that in the early stage after tumor transplantation, i.e., in the first or second week, regional lymph node cells showed a strong allogeneic inhibitory activity, as in the case with lymph-node cells from normal mice, but at progressive stage of cancer, i.e., the third or fourth week when tumors were larger, such activity was completely lost. It seems that mice with progressive cancer showed a decrease of allogeneic inhibitory activity, i.e., a disruption of homeostasis was present.


Chimeric analysis of hemopoietic cells after cross-sex parabiosis.

Anemia or polycythemia was induced in male rats. These males were conjugated with healthy, untreated female litter mates by FANG'S method of aortic parabiosis that resulted in complete cross circulation of blood between the two animals. The sex chromosomes of cells in erythropoiesis in various hemopoietic organs were examined in the treated male animals. The anemic parabionts indicated sharp increases in chimerical rates with erythroid marrows being evident. Polycythemic parabionts indicated marked decreases in chimerical rates with evidence of myeloid marrows. These findings suggested that the so-called stem cells in peripheral blood of the female parabiont migrated to the bone marrow of the male partner and that these migrating cells differentiated to erythroblast. The possible relationships between erythropoiesis and other cell proliferations in the hemopoietic organs are discussed.


Further studies on an eleventh case of heavy (Hgamma1) chain disease--clinical studies.

An eleventh case of heavy (Hgamma1) chain disease (Yok), surviving for more than 10 years and still living showed clinical and pathological findings similar to cases described in the past. The patient was given only glucocorticosteroids, ACTH, antibiotics and gamma globulin, as specific drugs. Precipitation arcs besides the major ones formed by albumin and Fc fragment were disclosed by immunoelectrophoresis. The existence of these minor components were confirmed with antigen-antibody crossed electrophoresis and Sephadex G-200 gel filtration. They did not form precipitation arcs with the other antigens available and they appeared in the same fractions of IgG on gel filtration suggesting their having higher molecular weight than the major ones. In addition to these findings, the clinical course of the patient is described.


Further studies on an eleventh case of heavy (Hgamma1) chain disease--physico-chemical studies.

An abnormal protein with similar antigenic properties to Fc fragments of IgG, was found in the serum and urine of an eleventh case of heavy (Hgamma1) chain disease (Yok). This protein was purified with ammonium sulfate precipitation and by column chromatography of DEAE cellulose, CM cellulose and Sephadex G-200. The purity of the protein obtained was 98.5%. It was crystallized easily, forming thin hexagonal plates of various sizes. The chemical compositions and physical properties of the protein including viscosity, partial specific volume, diffusion constant, sedimentation constant, frictional ratio, extinction coefficient and iso-ionic point are reported.


Further studies on an eleventh case of heavy (Hgamma1) chain disease--biosynthetic studies.

In vitro quantitative biosynthetic studies were carried out on bone marrow cells obtained from an eleventh case with gamma heavy chain disease. The findings indicate that neither cytoplasmic nor extracellular degradation was responsible for the presence of the gamma heavy chain fragment in serum. The absence of a covalent-bound light chain was also confirmed.


[A case of hypocholinesterasemia induced by trichlorfon].

A case of hypocholinesterasemia induced by ingestion of trichlorfon is presented. A female patient took 20 gm of this insecticide for the purpose of the suicide. She was brought to the hospital one hour later, and her life was saved by gastric lavage. Cyanosis on lips and nails, pupils with sluggish light reaction and fibrillary muscle twitch were observed upon arrival. Laboratory examination performed on the admission disclosed a serum cholinesterase activity of 0.3deltapH per hour. The enzyme activity was depressed to 0.05 deltapH per hour on the second day of hospitalization. The enzyme activity then increased gradually in the two subsequent weeks and the patient recovered.


The management of high-output intestinal fistulas.

A high-output gastrointestinal fistula is a surgical catastrophe of the first order of magnitude. Previously associated with an extraordinarily high mortality, the advent of parentaeral nutrition has markedly altered the management of these fistulas. Malnutrition and electrolyte imbalance formerly were the causes of death in the majority of patients. At the present time the mortality rate has decreased from approximately 40-60% to 6-20%, depending on the series. a suggested plan of therapy for high-output gastrointestinal fistulas is outlined. Good local care, sump drainage and nutritional support with or without the use of appropriate antibiotics, depending on the circumstances, are the keystones of management. Radiologic definition of the fistula is of primary importance. Certain criteria by which one may predict fistula closure aare outlined. The emphasis in this chapter is on an attempt at spontaneous closure with parenteral nutrition. In the event that this in not achieved, complete exclusion of the fistula from the gastrointestinal tract, either by excision or by total bypass, is mandatory to achieve satisfactory results. Causes of death remain sepsis and peritonitis related to the fistula, but an occasional patient will succumb to massive bleeding. Catheter-related sepsis and complications of hyperalimentation are largely preventable, and steps to prevent such complications are outlined.


Sedation of active acupuncture loci in the management of low back pain.

From 1971 to 1973 twenty-three consecutive patients with low back pain of undetermined etiology and two patients with arachnoiditis were treated by the sedation of active acupuncture loci located in the low back area. Sedation was accomplished by means of one to six injections of one-half milliliter of a local anesthetic at weekly intervals. Nineteen patients obtained complete relief and four patients were improved. The two patients with arachnoiditis showed no improvement.


Fibrin powder turbidity measurement for rapid assessment of antiplasmins.

Fibrinolytic activity was determined from the rate of disappearance of turbidity in a suspension of heat-treated fibrin powder. Using this method for estimating residual fibrinolytic activity in mixtures of serum and plasmin, antiplasmin behaviors of specimens from patients with various clinical disorders were determined after long and short preincubation times. Slow-acting antiplasmins were found to be increased in a variety of conditions among these patients, while immediate acting antiplasmins were generally decreased, compared with those in specimens from a large pool of normal, healthy vounteers. Normal women taking oral contraceptives had consitently high levels of slow antiplasmins. Tests in vitro showed that the antifibrinolytic agents epsilon-aminocaproic acid, Trasylol and soybean trypsin inhibitor act only as fast antiplasmins.


Congenital defects of the gastrointestinal tract and abdominal wall. A three-year review.

One hundred forty-four infants with anomalies of the gastrointestinal tract and abdominal wall were treated at Children's Memorial Hospital between July 1970 and July 1973. The overall mortality, including unoperated infants and those dying from other causes up to six months later, was 17%. Associated defects, particularly of the heart and CNS, were the most common causes for death. Many infants were premature; however, this factor alone did not contribute to mortality. Differences in surgical technique did not affect mortality in patients with esophageal atresia, but one baby with total aganglionosis of his colon and two with gastroschisis may have survived with different modes of therapy. Although previous advances in pediatric surgery contributed to the overall good results in these infants, parenteral alimentation emerged as the single most important factor in improved survival during this study period.


Double aneuploidy. Turner-Down syndrome.

Double aneuploidy involving Down and Turner syndromes is a rare occurrence. Of the six patients reported to have combined Down and Turner syndromes, four fundamentally different forms of chromosome mosaicism have been noted and all have been mosaic with respect to monosomy X. Reported here is the first example of a Turner-Down patient in whom there is no X mosaicism. The different forms of the double aneuploidy cannot be explained by any single combination of nondisjunctional errors. The clinical findings in these patients and the several mechanisms of nondisjunctional error that may account for the observed forms of aneuploidy are reviewed and discussed.


Recognition and reproduction of words by Down's syndrome and non-Down's syndrome retarded children.

Children with Down's syndrome were compared with other severely retarded children on tests of recognition and reproduction of real and nonsense words after 0-, 15-, and 30-seconds delay. The results indicated that Down's syndrome children performed better on the recognition task, but worse on the reproduction task after delay, as compared with the other retarded children. It was hypothesized that the articulatory deficit in the Down's syndrome group is part of a general motor disability due to a difficulty in preprogramming sequences of movements.


Dentition of monozygotic twins concordant for Down's syndrome: a case report.

Examination of the dental casts of Down's syndrome twins showed a high percentage of concordance and mirror-imaging relative to crown morphology and static occlusion. These supplemental dental findings supported an earlier diagnosis of monozygosity determined by other clinical means. Reduction of mesiodistal dimension of the dental crowns and deviations in their morphology is consistent with Down's syndrome.


Psychodynamics of the young handicapped person.

Psychodynamics of personality and ego development are related to motor development. The body image concept, important for normal psychologic performance is often impaired by somatic or cerebral defects. Adolescents are particularly depressed by loss of self-esteem and thwarting of future career goals. Sexuality is an important consideration for the handicapped.


[Method of rapid separation of free, sulfoconjugated and glucuronoconjugated fractions of plasma steroids].

A method for the separation of serum conjugated steroids, sulfates and glucuronides, is described. It is based on the fact that methylene blue forms complexes with ester-sulfates which can be quantitatively and specifically extracted by chloroform from aqueous phase. The quantitative determination of the conjugated fractions thus obtained can be done after solvolysis followed by hydrolysis by beta-glucuronidase from Helix pomatia.


Survey of helminth infections in Maine dairy cattle.

The survey was done to determine the incidence and seasonal prevalence of the gastrointestinal helminths infecting Maine dairy cattle. Approximately equal groups of calves, heifers, and cows from 13 dairy farms, managerially and geographically representative of dairying in the state, were sampled at regular 2-month intervals over the period of a year. On the basis of fecal egg counts and identification of cultured larvae, the following results were obtained: Of the 94 adult cows, 78 heifers, and 91 calves sampled continuously in the course of the survey, 95.7%, 98.7%, and 96.7%, respectively, were strongylorid positive (infected with Ostertagia, Cooperia, Trichostrongylus, Haemonchus, and Oesophagostomun), with an overall incidence of 97%. Strongyloides papillosus eggs were in 64.6% of the cattle, Bunostomum in 40.3%, Nematodirus in 27.8%, Trichuris in 27.0%, Capillaria in 9.5%, Moniezia in 25.1%, and Dictyocaulus viviparus larvae in 2.7%. Worm burdens, as reflected by mean nematode egg production per gram of feces, varied. The greatest worm burdens were in the calves, followed by the heifers and the cows. A marked variation in egg production related to season was observed, particularly with the strongylorid worms. Peak strongylorid egg production was observed in the May-June sampling period. After the peak period, worm burdens decreased in all groups of cattle to their lowest point during the winter period of January-February. This pattern of egg production was similar to that reported by workers in other parts of the world. Farm management practices were shown to be related to the degree of parasitism existing in these herds. Those herds classed as poorly managed had significantly higher levels of parasitism in young animals than those classed as having fair or good management.


Clinical and experimental studies on adenine, various nucleosides and their analogs in hematology.

In red blood cells as well as in platelets there appears to be a decrease in adenine nucleotides during storage under blood bank conditions. This can be decreased by use of anticoagulant preservatives with higher phosphate content than the standard ACD solution, through the addition of adenine and inosine. Maintenance of higher ATP levels appears to be related to longer circulating life span after transfusion into patients in the case of red blood cells but not platelets. Inosine and more alkaline preservative medium also contribute to the maintenance of 2,3-DPG levels in red blood cells, and with it to the maintenance of normal hemoglobin dissociation curves and thus oxygen-carrying capacity. Certain nucleoside analogs may contribute to the preservation of platelets and of whole blood by their platelet-aggregation inhibitory activity. Platelet-aggregation inhibitors may also be useful in preventing thromboembolic episodes with potentially greater safety than anticoagulants.


A family with three sibs carrying trisomy 21.

A family with three sibs, including a pair of dizygotic twins, all affected by Down's syndrome with regular trisomy 21, is described. The chromosome counts carried out on prolonged fibroblasts cultures of the mother, revealed the presence of the trisomy 21 in 6 out of 688 scored mitoses. The cytological findings give support to the hypothesis of a chromosome mosaicism in one of the normal parents, as a cause of the recurrence of the trisomy 21.


[Proceedings: Therapeutic possibilities of deshydroepiandrosterone in faetal hypotrophy (author's transl)].

The therapeutic effect of DHEA-S has been studied in 15 cases of intra-uterine growth retardation. This double-blind study has not been able to demonstrate any difference between the effect DHEA-S and of NaCl on oestriol excretion, HPL values, and biparietal diameter. Only the uterine growth seems to be affected by DHEA-S. Thus it can be concluded that DHEA-S has no therapeutic effect on placental insufficiency.


Amplified developmental instability in Down's syndrome.

It is suggested that the extra chromosome in Down's syndrome (DS) results in a generalized decrease in canalization of development. Three palatal dimensions - height, width and anteroposterior length - were measured in moreal twins and in DS subjects. Twin analyses showed that the relative contribution of environmental factors to variability was greatest for palatal length. Of the three dimensions, palatal length was the most abmoreal in DS. Similarly, the maximum atd angle, which is more susceptible to environmental variation than the finger-tip ridge count, is much more deviant from the normal in DS. In both systems the less-stable trait in moreal populations in norm abnormal in DS. These data are consistent with a generalized amplified instability of development in DS.


[Proceedings: Male pseudohermaphroditism due to testicular 17 beta hydroxysteroid deshydrogenase deficiency (author's transl)].

A new case of 17 beta hydroxysteroid deshydrogenase deficiency is reported. In venous blood, dehydroepiandrosterone (DHA) level is normal, but the level of basal testosterone (T) is low, and delta 4 androstenedione (delta 4 A) is ten times higher than the normal level. The increase of delta4AT is characteristic after chorionic gonadotropin stimulation and over more in spermatic venous blood. Estrone (E1) produced from delta 4 A is high but estradiol (E2) level is equally low in systemic circulation and spermatic venous blood. This increase of plasmatic E2 is the witness of disturbance of E1 conversion into E2 as well as delta 4 conversion into T. It is an explantation of the lack of gynecomastia in this case. Serum gonadotropins LH and FSH are increased. This report contrast with other cases of 17 beta hydroxysteroid deshydrogenase deficiency and with the testicular feminization in which E2 and FSH levels are normal. This underline the importance of T in the LH regulation and the one of E2 in FSH control.


[Effect of cerebral serotonin on cyclic LH release in rats].

An experimental increase in serotonin (5-HT) induced shortly before the "critical period" of ovulation control blocks the release of LH. Administration of a synthesis inhibitor of the amine p-chlorophenylalanine, (pCP) is ineffective when given during the critical period. However, pCP given in the evening of dioestrus II (18 to 24 hours before the "critical period") blocks ovulation. That 5-HT is specifically involved in this delayed effect of the drug is shown by the ability of increasing doses of 5-hydroxytryptophane (5-HTP) to induce with pCP a graded restoration of LH release when given together. This result, obtained in immature rats, has been confirmed in cyclic ones. A positive, permissive effect of 5-HT containing neurons on neural processes leading to LH release and ovulation is thus postulated. This action affects early stages of the LH release regulating mechanisms, in contrast to the classically described inhibiting effect of the amine, which blocks the actual release of LH-RH at the median eminence level during the critical period.


[Proceedings: Effects of metopirone on plasma androgens variations in women (author's transl)].

Blood testosterone (T), androstenedione (A) and dehydroisoandrosterone (DHA) were simultaneously measured, using radioimmunoassay, in six healthy (control) females and eight various subjects, before (J1), during (J2) and after (J3) metopirone administration. The variation pattern of each androgen is different during the test. The mean value of each androgen at each time, point and the percentage decrease between J2 and J3 related to J2 are considered. Each step of the test (increase and decrease) is discussed with reference to published data and variations of response obeserved in the eight non control subjects.


Benefits to Down's syndrome children through training their mothers.

This study investigated the hypothesis that training of mothers with Down's syndrome children would be beneficial both to the child and parents. The mothers were taught behaviour modification techniques based on learning theory and were given group discussions on dealing with their family or personal problems. The subjects were 16 mothers with a Down's syndrome child, divided into two groups on the basis of their child's sex and chronological and mental ages. The Griffiths Scale was used for assessment. The mothers in the treatment group received 12 sessions of training and group counseling over a 6-month period, whereas the control mothers received no additional attention except the usual routine from the general practitioner and health visitor. The result show clear gains to both the child and mother in the treatment group. The child improved, especially in language development as well as in the other areas, and the mother-gained more confidence and competence in her daily management of the child.


Infrared spectroscopy for tracing of topically applied ointment vehicles and active substances on healthy skin.

Infrared spectroscopy was used to trace active substances and ointment vehicles applied on the skin. Vaseline and lanoline could be traced after 8 hrs but not olive oil. From the active substances, ethyl-4-amino-benzoate (5 per cent), clioquinol (5 per cent), parabenes (15 per cent), 5,7-dichlor-8-hydroxy-2-methyl-chinolin (5 per cent), balsam of Peru (25 per cent) and pyroleum pini (12 per cent) could be traced 1 hr after application but had disappeared after 8 hrs. Ethylenediamine (1 per cent), chlorcresol (1 per cent), pyroleum lithantracis (5 per cent), were not traceable after 1 hr, and curiously neither neomycine sulphate in spite of its high concentration (20 per cent). The reaction of the skin surface lipids, after application of different substances, was deduced from the spectra. Clioquinol and pyroleum lithantracis seem to give rise to hydrolysis of the triglycerides, the free fatty acids being clearly identifiable. It is felt that infrared spectroscopy can be used as an effective method to trace different substances such as potent allergens on healthy or diseased skin.


[Kinetics of cell proliferation in normal epidermis before and after application of 1 per cent vitamin A-acid solution (author's transl)].

A 1 per cent Vitamin A-acid solution was applied externally for 2 weeks on normal epidermis. The result was an acute dermatitis, characterized by hyperproliferation and shortened phases of cell cycle. There was no increase in the proliferative activity of lymphoid cells in the moderate dermal infiltrate.


Breakdown of proteoglycan and collagen induced in pig articular cartilage in organ culture.

Explants of articular cartilage from young pigs were maintained in organ culture for 10--16 days, and degradation of matrix was induced by retinol or complement-sufficient antiserum. The percentage breakdown of proteoglycan and collagen (as hydroxyproline release) was measured. The response of the cartilage depended on whether or not the explants were cut so as to include some of the invading marrow ('invasion zone'). In media containing retinol, cartilage lost up to three-quarters of its proteoglycan whether the invasion zone was present or not, but very little of its collagen unless this region was included. In the presence of complement-sufficient anti-serum, however, cartilage without the invasion zone was virtually unaffected, but both proteoglycan and hydroxyproline were released when invasion zone was included; here proteoglycan release began almost immediately, but there was a time-lag of 6--8 days before a substantial amount of hydroxyproline appeared in the medium. Histological examination of sample explants from the experiments supported the biochemical findings. The possible significance of the results in relation to rheumatoid arthritis is discussed.


Presence of endothelium in an axillary-femoral graft of knitted Dacron with an external velour surface.

An axillary-bilateral common femoral graft of knitted Dacron with an external velour surface was examined within one hour after the patient's death from non-graft-related causes. The prothesis, implanted for 20 months, was patent and was completely healed over 32% of the flow surface--that is, full wall fibrous tissue encapsulation of the graft had occurred, and 32% of the flow surface was endothelialized. The remaining flow surface was formed of fibrin, but fibrous tissue healing had reached the inner surface of the graft material, and the fibrin overlay was very thin. The healed protions of the graft included not only the areas adjacent to the anastomoses, but were scattered throughout the 45 cm length of the prosthesis. To our knowledge, this is the first report of complete healing (fibrous tissue encapsulation and endothelialization) documented at points beyond the plannus ingrowth at the prosthesis-artery anastomosis.


Bypass grafts for recurrent or complex coarctations of the aorta.

Twenty-three patients aged 5 to 53 years with recurrent or complex coarctations of the aorta were successfully operated upon using bypass grafts. This technique of repair was selected for 5 patients with recurrent coarctation, 11 with long-segment coarctation with or without hypoplasia of the transverse aortic arch, and 7 with inadequate collateral circulation. Nineteen patients had bypass grafts from the left subclavian artery to the distal descending thoracic aorta. The other 4 had a combined approach through a left thoractomy and median sternotomy with grafts between the ascending and descending thoracic aorta. All patients survived the operative procedure. One patient were reexplored for a hemothorax and 5 developed transient postoperative hypertension. There were no instances of abdominal vasculitis or lower extremity paralysis. These patients have been followed from 3 months to 11 years postoperatively, and all but 1 are alive and well. Twenty-two are normotensive, and none have the sequelae of hypertensive disease. Gradients up to only 15 mm Hg exist between upper and lower extremity blood pressures. Five patients have undergone postoperative catheterization and aortography, and all have patent grafts. This procedure is a useful and adjunct in difficult coarctations of the aorta and can be safely performed with excellent reproducible long-term results.


A method for rapid tailoring of the intraatrial baffle in transposition of the great vessels.

Numerous reports have described successful use of the Brom "trouser-shaped" baffle in the Mustard procedure. A simple technique to fashion the baffle accurately by use of a prefashioned template is described.


A comparison of drug-induced rotation in rats lesioned in the medial forebrain bundle with 5,6-dihydroxytryptamine or 6-hydroxydopamine.

Drug-induced rotational behaviour was studied in two groups of rats with differing chemical lesion of the right medial forebrain bundle (MFB). 6-hydroxydopamine (6-OH-DA), 3.5 mug, injected in one group, induced a marked lowering of dopamine (DA) and noradrenaline (NA) in the right hemiforebrain. 5,6-Dihydroxytryptamine (5,6-HT), 10 mug, injected in a second group, produced a profound and long-lasting depletion of 5-hydroxytryptamine (5-HT) and DA, but not of NA. Rotational behaviour induced in both groups by DA receptor agonists (apomorphine, piribedil, L-DOPA, ergometrine, ergocornine, 2-bromo-alpha-ergocryptine, ergocristine, methylergometrine) and agents releasing DA (d-methamphetamine, methylphenidate) were qualitatively identical and quantitatively very similar, suggesting a minor role of 5-HT striatal terminals in these experimental conditions. LSD induced contralateral rotation by direct stimulation of the DA receptor, while L-5-hydroxy-tryptophan (L-5HTP) was inactive.


Antagonism of d-lysergic acid diethylamide and mescaline by 1-methyl-1, 2, 5, 6-tetrahydropyridine-N, N-diethyl-carboxamide (THPC).

Contractions of sheep umbilical vasculature induced by 5-hydroxytryptamine, mescaline and d-lysergic acid diethylamide (LSD) were antagonized by 1-methyl-1, 2, 5, 6-tetrahydropyridine-N, N-diethyl-carboxamide (THPC) 5 X 10(-4)M. THPC did not block contractile responses to angiotensin. The data are interpreted to support our previous suggestions that certain chemical entities representing portions of the LSD molecule may be effectively studied as antagonists to the hallucinogens. The present data indicate that THPC is a weak 5-hydroxytryptamine receptor antagonist.


Catabolism of D-fructose and D-ribose by Pseudomonas doudoroffii. I. Physiological studies and mutant analysis.

Pseudomonas doudoroffii, a strict aerobe of marine origin, was able to utilize fructose and ribose but not glucose, gluconate, or other hexoses, pentoses, or sugar alcohols as sole sources of carbon and energy. Evidence was presented indicating that in this organism fructose was utilized via an inducible P-enolpyruvate: fructose phosphotransferase system (FPTS) which catalyzed the phosphorylation of fructose in the 1 position. The resulting fructose-1-P (F-1-P) was converted to fructose-1,6-P2 (FDP) by means of an inducible 1-P-fructokinase (1-PFK). The subsequent conversion of FDP to pyruvate involved enzymes of the Embden-Meyerhof pathway (EMP) which, with the exception of glyceraldehyde-3-P dehydrogenase (G3PDH), were constitutive. Two G3PDH activities were detected, one of which was inducible and NAD-dependent while the other was constitutive and NADP-dependent. Cell-free extracts of P. doudoroffii also contained enzymes of the methylglyoxal pathway (MGP) which converted dihydroxyacetone-P to pyruvate. The low specific activities of enzymes of this pathway as compared to the EMP suggested that the major route of FDP catabolism was via the latter pathway. 2. Ribose catabolism appeared to involve an inducible uptake system and an inducible ribokinase, the resulting ribose-5-P being converted to glyceraldehyde-3-P and fructose-6-P (F-6-P) by means of constitutive activities of the pentose-P pathway. The F-6-P formed as a result of these reactions was converted to FDP by means of a constitutive 6-P-fructokinase (6-PFK). Since no activity converting fructose or F-1-P to F-6-P could be detected in cell-free extracts of P. doudoroffii, the results suggested that fructose and ribose were catabolized via 1-PFK and 6-PFK, respectively, the two pathways converging at the level of FDP. Further evidence for this suggestion was obtained from a mutant which lacked an NAD-dependent G3PDH, accumulated FDP from both fructose and ribose, and was not able to grow on either of these compounds. 3. Ribose grown cells had increased amounts of the fructose uptake system and 1-PFK suggesting that a compound (or compounds) common to the catabolism of both fructose and ribose acted as the inducer(s) of these activities. Evidence was presented suggesting that the probable inducer(s) of 1-PFK and FPTS could be FDP, glyceraldehyde-3-P, or dihydroxyacetone-P. 4. A mutant unable to grow on fructose was characterized and found to lack FPTS while retaining 1-PFK and other enzyme activities of the EMP and MGP, indicating that a functional FPTS was essential for growth on fructose and suggesting that all or most of this sugar was catabolized via F-1-P.


[Corticosuprarenaloma in children].

Thirty-four cases of corticosurrenaloma with clinical onset before 15 years of age have been studied. Higher frequency in girls (65 percent of the cases) and in young age (80 percent before 5 years of age, 43 percent before 2 years), association with personal or familial other tumors and malformations, are noticeable features. Virilism is the major manifestation in children (83 percent of the cases), either isolated or associated with hypercortisolism and/or feminization. Hormonal assays are of little value, and the dynamic adrenal tests are of some help only in small tumors or isolated hypercortisolism. Radiological diagnosis by urography with cavography, arteriography, is easy in most cases. Evaluation of prognosis is very difficult. Clinical and biological data are not significant, histological data are often of little help. Only a very large mass, and occurrence of metastases (liver, lungs) evidence malignancy. This series does not allow to assess definitely the best therapeutic regimen. Surgery has to be performed as soon as possible. The effects of radiations have not yet been ascertained. High doses of op'DDD have led to a sustained remission of the tumor or metastases in 2 patients, and perhaps to a longer survival in 4 others.


The representability of laparoscopic ovarian biopsies for the cellular structure and function of the ovaries.

Model biopsy specimens from 100 surgically removed ovaries were studied. They were matched in respect of size, dimensions and examination technique to 110 ovarian biopsy specimens obtained during laparoscopy from 60 amenorrhoeic patients. It was found that ovarian biopsy specimens with an all-round edge length of 4 to 5 mm permit usable conclusions in respect of the structure and hence also of the function of normal ovaries.


Crossover femorofemoral grafts followed up five years or more. An analysis.

Crossover femorofemoral grafts continue to provide satisfactory long-term patency with low morbidity and mortality in the treatment of unilateral atherosclerotic iliac artery occlusion. In our series of patients, early failures were primarily a result of the inability to provide adequate runoff for the graft, and late failures were due to progressive atherosclerotic involvement of runoff vessels. Clear-cut progression of the atherosclerotic process in the donor iliac artery segment has not been observed in this series. In fact, there is evidence that suggests that this process may have been retarded when compared with other types of reconstructive procedures. There is a noticeably late mortality (33%) due to other disease processes and associated cardiovascular disorders. These facts continue to support the application of crossover femorofemoral grafts in the surgical treatment of unilateral atherosclerotic illiac artery occlusions.


The natural history of bilateral aortofemoral bypass grafts for ischemia of the lower extremities.

Analysis of the immediate and long-term results in 180 patients undergoing aortofemoral bypass grafts for occlusive disease of the lower extremities showed the immediate graft limb patency in 360 graft limbs to be 99.2%. The cumulative ten-year graft limb patency was 66%. Factors associated with thrombosis of the graft limb revealed correlations for localized atherosclerotic disease of either the profunda femoris artery or the tibial trifurcation vessels. The highest correlation for graft limb thrombosis was with simultaneous lesions involving both the profunda femoris artery and tibial trifurcation vessels. The acute lower extremity salvage rate was 94%, and the ten-year cumulative extremity salvage for legs at risk of amputation was 85%. Postoperative symtpoms correlated well with patency. Overall operative mortality was five patients out of 180 (2.5%).


New apparatus and method for the toxicological investigation of metered aerosols in rats.

A new apparatus and method for the toxicological investigation of metered aerosols in rats, which is also suitable for tests in other small laboratory animals, is described. It permits: 1. simultaneous treatment of 5 or more animals, 2. administration of metered aerosol doses to individual animals, 3. ventilation of the cages, 4. mechanical tilting of the metered aerosol packs to ensure thorough mixing of the content, and 5. continuous automatic tilting, administration and ventilatied under different ventilation conditions. Blood gases and fluorinated chlorohydrocarbons (abbreviation: fluorocarbons) in the arterial blood were also determined. In tests with spontaneous ventilation of the animal chambers without positive pressure, significant acidosis and hypoxia occurred after 40 puffs of metered aerosol. Where ventilation of the chambers was insufficient, the fluorocarbons led to dose-dependent toxic and lethal effects. The substance and the additives contained in the metered aerosol did not interfere with these effects. After active ventilation with 0.5 atm no symptoms of acidosis or hypoxia were observed. Up to 160 puffs of metered aerosol, no indications of toxic effects were established in the rats. Half-life of the fluorocarbons in the arterial blood after one puff of metered aerosol was 69 to 80 sec for fluorocarbon 11 and 57 to 67 sec for fluorocarbon 12.


[Sex and type peculiarities of the topography of the anterior abdominal wall in adult persons of various ages].

In men and in "masculine" shape of the abdomen as compared with women and "feminine" shape of the abdomen the following features of the topography of the anterior-lateral abdominal wall were revealed: a narrower white line, wider straight muscles of the abdomen in their medial and upper parts, less square surface of the lateral muscle-free portions. The inguinal region of men and the "musculine" type of the abdomen are characterized by great dimensions of the superficial and profound rings, weaker aponeurosis of the external oblique abdominal muscle in formation of the anterior wall of the inguinal canal. In elderly and senile age there occur dilatation of the white line, the increase of the amount of chinks and apertures in it as well as of the length of aponeuroses. The superficial inguinal ring expands.


[Formalin-free method of preserving endocrine glands of the branchiogenous group (thyroid, parathyroid and thymus)].

The authors propose a conservation method developed at the Department of Normal Anatomy of the Pavlov First Medical Institute. The conservation is performed by simultaneous using of chemicals upon which the method is based: conservant and latex. The conservant is a mixture of glycerine, potassium acetate and water in proportion 45% : 10% : 45%. The latex is industrial artifical rubber.


[Morphological changes in triploidy in human ontogeny].

Cytological and morphological data of 187 spontaneous abortuses, 25 fetuses and infants with triploidy described in literature and 6 proper triploid abortuses were analyzed. It was established that in spite of polymorphism of phenotypical manifestations of triploidy in ontogenesis there are a number of permanent, often combining morphological changes (asymmetry of the body, syndactylism of the III--IV fingers and toes, anomalies in the nervous and genito-urinary system). These features in addition Institute of Medical Genetics, USSR Acad. Med. Sci., and Institute of Obstetrics and Gynecology, Ministry of Health, USSR. To dysplasias present in other chromosomal disorders, allow establishing the syndrom of triploidy in man and to diagnose the disease with great probability. Hydropic and cystose degeneration of the chorion villi met in 85% of cases of triploidy has but external resemblance with true vesicular mole which has normal karyotype. Cytogenetical and morphofunctional differences between them were noted.


The left ventricle in anomalous pulmonary venous return. Morphometric analysis of 36 fatal cases in infancy.

The mass of the left ventricle is normal in infants with total anomalous pulmonary venous return, but the ventricular cavity is compromised by leftward displacement of the interventricular septum due to the combined pressure-volume overload of the right side of the heart. Severe septal displacement is associated with distorted myocardial architecture in the region of the septal attachments of the left ventricular free wall. Abnormalities of septal motion are frequently detected in echocardiograms. Left ventricular output is low, as judged by arrested development of the aortic valve circumference, and is probably compromised both by the left to right shunt and by septal displacement. Successful correction of the anomaly may depend on intervention before the changes in septal position, structure, and function have become irreversible.


Enzymes of Neurospora crassa which attack UV-irradiated DNA.

Two excision-deficient mutants of Neurospora crassa contain normal levels of two enzymes, a single-strand-specific exonuclease and a single-strand specific endonuclease, which attack UV-irradiated DNA. Mutants of N. crassa have been obtained in which the activity of the latter enzyme as well as an activity with native DNA are simultaneously affected. These activities are also apparently low in excision-proficient uvs3 strain of N. crassa which has many of the characteristics of the recA mutants of E. coli.


Faulty DNA repair following ultraviolet irradiation in Fanconi's anemia.

Fibroblasts from a patient with Fanconi's anemia were deficient in their ability to excise UV-induced pyrimidine dimers from their DNA but were capable of single-strand break production and unscheduled DNA synthesis.


Macromolecular properties and end-group analysis of heparin isolated from bovine liver capsule.

Glycosaminoglycans were extracted from bovine liver capsule with 4 M-guanidinium chloride, resulting in solubilization of approx. 90% of the total uronic acid-containing polysaccharide of the tissue. The extracted polysaccharide was purified and fractionated by anion-exchange chromatography on DEAE-cellulose, density-gradient ultracentrifugation in CsCl and finally gel chromatography on Sepharose 4B. By using these procedures, the two major polysaccharide components, dermatan sulphate and heparin, which constituted 55 and 30% respectively of the total glycosaminoglycan content of the tissue, were separated from each other. Analysis of the macromolecular properties of the two polysaccharides showed that heparin existed exclusively as single polysaccharide chains, whereas dermatan sulphate occurred largely as a proteoglycan (protein content, 74% dry wt.). The purified heparin preparation was subjected to sedimentation-equilibrium ultracentrifugation, indicating a molecular weight of 8800. Analysis for neutral sugars (by g.l.c.) showed 0.1 residue of xylose and 0.2 residue of galactose/polysaccharide chain; serine amounted to 0.3 residue/polysaccharide chain. Reduction of the heparin with NaB3H4 resulted in incorporation of 3H, approximately corresponding to one reducible group/polysaccharide chain. The 3H-labelled sugar residue was liberated by a combination of acid hydrolysis and deaminative cleavage of the polysaccharide with HNO2; it was subsequently identified as an aldonic acid by paper electrophoresis. Most of the heparin chains thus contained a uronic acid residue in reducing position. It is suggested that heparin isolated from bovine liver capsule is a degradation product released from larger molecules by an endo-glycuronidase.


Mechanism of action of colchicine. III. Antiinflammatory effects of colchicine compared with phenylbutazone and indomethacin.

Colchicine suppresses the development of carrageenan-induced edema in the rat with a minimum effective oral dose of 6.0 mg/kg. The slope of the dose-response regression line for colchicine differs significantly from that of indomethacin and phenylbutazone. Based on the dosages required to achieve a 50% suppression of this inflammation, colchicine is 0.6 and 1.5 times as potent as indomethacin and phenylbutazone, respectively. In the reversed passive Arthus reaction in the rat, the suppressive activity of colchicine is at least 50 times that of indomethacin and 100 times that of phenylbutazone. The possible significance of these results with regard to the unique effectiveness of colchicine in the treatment of gout is discussed.


Factors predisposing to postural hypotensive symptoms in the treatment of high blood pressure.

Symptoms due to orthostatic and exertional hypotension occurred in 23-4 per cent of 448 hypertensive patients treated with guanethidine, debrisoquine, or bethanidine. Symptoms were significantly more frequent in patients treated with guanethidine than in those treated with bethanidine or debrisoquine. Women rather than men and patients with radiological evidence of cardiomegaly, electrocardiographic evidence of left ventricular hypertrophy, or ST/T wave changes, developed these symptoms significantly more often than other patients. A raised blood urea was found more frequently in patients with postural hypotensive symptoms. Characteristically guanethidine produced early morning postural hypotensive symptoms, wheras hypotensive symptoms caused by bethanidine and debrisoquine occurred at other times of the day and particularly one to two hours after tablet ingestion. Debrisoquine and guanethidine had a significantly greater negative chronotropic effect than bethanidine. It is suggested that negative chronotropic effects of these drugs may potentiate hypotensive symptoms in patients with cardiovascular, renal, or cerebrovascular disease. It should be possible to minimize symptoms of postural hypotension by attention to predisposing factors and selection of treatment accordingly.


Heredity in primary endocardial fibroelastosis.

Twenty-six cases of endocardial fibroelastosis were collected from three hospitals in Manchester over a ten-year period. Nine cases occurred in 4 families and these are discussed in detail. X-linked recessive inheritance seems likely in one family in which two probable female carriers had subarachnoid haemorrhages. In a second family an apparently normal man produced two children with endocardial fibroelastosis by different mothers suggesting autosomal dominant inheritance with incomplete penetrance. Autosomal recessive inheritance may be involved in the remaining two families but this was not associated with consanguinity. Genetic heterogeneity is evident in endocardial fibroelastosis and the majority of cases occur sporadically. An accurate family history is therefore necessary but it is difficult to give precise recurrence risks in sporadic cases.


Premature opening of aortic valve in severe aortic regurgitation.

Premature opening of the aortic valve in late diastole has been demonstrated by echocardiography in a patient with severe aortic regurgitation. Valve opening coincided with the end of the diastolic murmur and equalization of aortic and left ventricular diastolic pressures. Echocardiography of the aortic valve in severe aortic reflux may, therefore, provide valuable information about the underlying haemodynamic disturbance.


Serial studies of pulmonary stenosis in infancy and childhood.

Thirty-five children with pulmonary stenosis were catheterized from 1 day to 9 years of age and recatheterized after 2 weeks to 15 years. Right ventricular systolic pressure rose in 24 and the increase was greater in those under than over 5 years old. Pulmonary valve orifice area per square metre of body surface area increased in 12, but did not change in 3, and fell in 17; absolute decrease in calculated orifice area was usually associated with infundibular hypertrophy. Increase in right ventricular systolic pressure with age was thus caused by failure of the valve orifice to grow fast enough to keep pace with the increase of stroke volume. In the whole group, increasingly severe pulmonary stenosis was matched by increasing electrocardiographic evidence of right ventricular hypertrophy. However, in individual patients the electrocardiogram could suggest that right ventricular pressure had decreased when in fact it had risen considerably.


Heart disease caused by Coxsackie virus B infection.

A study of 55 patients with heart disease suspected of being viral in origin was carried out a Medical College Hospital, Nagpur, over a period of 2 years. Virus studies as well as other routine tests were carried out on all patients. In 19 patients a virus aetiology of the heart disease was proved by isolation of one of the subtypes of Coxsackie B virus and/or on the basis of fourfold rise in neutralizing antibody titre in paired sera. Of these patients, 5 had acute myocarditis and 5 had acute myopericarditis; 3 had acute pericarditis; 3 had congestive cardiac failure of obscure aetiology; 2 had pleuropericarditis, and the remaining 1 developed post-partum heart failure with cardiogenic shock. All had electrocardiographic abnormalities. Thirteen had cardiomegaly; 1 had a right-sided pleural effusion and 2 had pericardial effusion. Virus could not be isolated from pericardial fluid or pleural fluid in these 3 patients. Follow-up studies up to 10 weeks from discharge revealed that 8 patients were clinically normal but 4 of these 8 had persisting ST-T wave changes, and in 4 the electrocardiogram had returned to normal. Of the remaining 11 patients, 3 had persistent chronic heart failure, 3 had vague symptoms of praecordial pain but no abnormal signs, and 5 patients were lost to follow-up.


Localized left ventricular myocardial defect leading to fatal cerebral embolism.

The case of a previously health 17-year-old youth who presented a fatal cerebral infarct is described. A localized defect in the anterior left ventricular myocardium with overlying thrombus, and left ventricular hypertrophy were found at necropsy. An old infarct was found in the left kidney. There were no signs of ischaemic or inflammatory heart disease. The possible origins of the lesion are discussed.


Coarctation of aorta with right aortic arch. Report of surgical correction in 2 cases: one with associated anomalous origin of left circumflex coronary artery from the right pulmonary artery.

Two patients with right aortic arch, anomalous left subclavian artery, and coarctation of theaorta, have been operations for the relief of coarctation, successful in one but only partially successful in the other: in one case, a 'dacron' patch was inserted into the narrowed segment, but a mild recurrence of coarctation was found a year later; in the other, the proximal segment of the anomalous left subclavian artery was used for the repair, with complete relief of the coarctation, both immediately and at late follow-up. The first case had multiple associated congenital abnormalities, including anomalous origin of the left circumflex coronary artery from the right pulmonary artery, which was also corrected surgically: this anomaly has only been recorded once hitherto. The second had facial haemangiomata and a small ventricular septal defect. Four previously reported cases of coarctation and right arch are reviewed. These 6 cases are considered in the light of current views on the development and classification of aortic arch anomalies.


Echocardiographic left ventricular dimensions in pressure and volume overload. Their use in assessing aortic stenosis.

Left ventricular 'relative wall thickness', determined from the ratio between echocardiographic measurements of end-systolic wall thickness and cavity transverse dimension, was related to peak systolic intraventricular pressure in 15 normal subjects, in 15 patients with left ventricular volume or pressure overload without aortic stenosis, and in 23 patients with aortic stenosis. All these patients had a mean rate of circumferential fibre shortening greater than 1.0 circumference per second and were regarded as having good ventricular function. Relative wall thickness was found to be normal in cases of volume overload and to be increased in pressure overload, being proportional to the systolic intraventricular pressure. Values for the ratio of systolic intraventricular pressure to relative wall thickness in the normal subjects and patients without aortic stenosis were similar (mean 30 +/- 2.5). Based on this relation, estimates of peak systolic intraventricular pressure were made in the cases of aortic stenosis using the formula: systolic intraventricular pressure (kPa) equals 30 x wall thicknes divided by transverse dimension. Peak systolic aortic value gradients derived by subtracting brachial artery systolic pressure, measured by sphygmomanometer, from the echocardiographic estimates of intraventricular pressure compared favourably with the gradients measured at left heart catheterization (r equals 0.87, P less than 0.001). Aortic value orifice areas, derived from echocardiographic estimates of stroke volume, ejection time, and value gradient, ranged from 0.21 to 3.16 cm2 and appeared to correlate with the severity of aortic stenosis. All patients with aortic stenosis, with or without coexistent mild aortic regurgitation, who were recommended for aortic valve surgery, had estimated valve orifice areas of less than 0.8 cm2. A further 10 patients with pressure or volume overload had mean rates of circumferential fibre shortening of less than 1.0 circumference per second and were regarded as having poor ventricular function. In these cases values for relative wall thickness were lower than in those with good ventricular function and were not proportional to systolic intraventricular pressure. In patients with good left ventricular function systolic intraventricular pressure is proportional to, and can be estimated from, echocardiographic measurement of relative wall thickness.


Induction of an autologous immune complex glomerulonephritis in the rat by intravenous injection of heterologous anti-rat kidney tubular antibody. III. Long-term effects.

The long-term effects of a single intravenous injection of anti-rat kidney fraction 3 antibody were studied in rats. At the end of the experiment at one year the kidneys had deposition of immune complexes in the glomeruli staining for autologous IgG and C-3. The number and size of the deposits did not appear to increase during the experiment although proteinuria eventually developed in most test animals. Control rats injected with normal rabbit serum had no immune complexes in their kidneys.


Prealbumin bearing lymphocytes as an indicator of hapten protein carrier in certain varieties of dermatitis.

Patients with dermatoses where the antigen is a hapten, such as those with contact eczema and drug allergy, had high mean values of lymphocytes with membrane bound prealbumin detected by immunofluorescence methods. These results support the hypothesis that lymphocytes bind prealbumin. We speculate that this was haptenized prealbumin.


Rosacea of common male baldness.

Four patients are described in whom rosacea occurred on the face, and on the scalp in patches of baldness. Histopathological examination of the specimens taken from the scalp showed changes of rosacea and basophilic degeneration of collagen. In two patients direct immunofluorescence studies were performed; in one of these the presence of IgG deposits at the dermo-epidermal junction was demonstrated. These observations confirm the influence of external factors in the pathogenesis of rosacea.


The deoxyribonucleic acid (DNA) skin test in systemic lupus erythematosus. 2. Histological findings.

A total of fifty-five biopsies from fifty-two intradermal DNA skin tests were studied. The biopsies were taken, 6, 8-10, 24 or 48 h after the injection of the DNA material. Necrosis of the vessel wall was taken to be the main characteristic of a specific reaction. In forty of the fifty-two tests the results of the histological evaluation closely matched the clinical results. In five of the fifteen cases with discrepancies, the histological evaluation ruled out clinically false positive test results. In three cases of SLE on corticosteroid treatment, the histological examination gave a positive result despite a clinically negative result. In seven of the fifteen cases the discrepancies occurred in borderline cases with reactions of 5 to 6 mm diameter. The amount of inflammatory cells in positive as well as in negative reactions was also recorded. The number of polymorphonuclear cells in positive reactions increased with the age of the reaction. The number of lymphocytes was not found to increase in the positive reactions, thus differing from the delayed hypersensitivity type of reactions. Rather, the reaction was characterized by an Arthus type of hypersensitivity. On the basis of the present study it may be concluded that clinically positive tests at 6 or 8 h may merely be expressions of nonspecific vascular alterations. On the other hand, in late reactions, even in patients on systemic treatment, histological examination revealed clinically negative results to be positive. By using the histological picture of hypersensitivity angiitis as the main diagnostic criterion the specificity of the clinical reactions may be established.


Isolation and properties of a low molecular weight antiplasmin of human blood platelets and serum.

A low molecular weight antiplasmin has been detected in human blood platelets. The antiplasmin is dialysable and a similar material is present in normal plasma. A simple method for rapid isolation of the antiplasmin based on ultrafiltration is described. The inhibition of plasmin by these materials under different conditions has been studied. In the ultracentrifuge, both antiplasmins showed a single broad peak with an approximate sedimentation coefficient of 0.5S. Paper chromatography and paper electrophoresis indicated the isolated material to be heterogeneous. The individual components were isolated by paper chromatography and the antiplasmin activity was measured by the fibrin plate method. Preliminary studies on the fraction with maximal antiplasmin activity suggest that the inhibitory effect might be due to enzyme-inhibitor complex formation. Based on the present data, it is concluded that the platelet antiplasmin and the serum antiplasmin are very similar. This antiplasmin material may be useful in fibrinolytic therapy.


A solid-phase radioassay for the quantitative determination of antiplasmin activity in human plasma.

The caseinolytic activity of one CTA (Committe on Thrombolytic Agents) unit of human plasmin is inhibited by a series of plasma dilutions containing antiplasmin. Then neutralization of the standard plasmin by increasing amounts of antiplasmin shows a steeper linear decrease of plasmin activity betwwen 1.0 and 0.5 CTA units and a much smaller further inactivation below 0.5 CTA units. It is thought that the standard plasmin is partially damaged at the antiplasmin combining site during the purification procedrue and might be responsible for the differences in plasmin-antiplasmin neutralization in the standard curve. Using the steeper slope of the plasmin neutralization curve, an average of 8.6 +/- 1.0 CTA units plasmin neutralizing activity per ml human plasma was found in 36 healthy donors. The difficulty of obtaining 'native' standard plasmin with full antiplasmin combining capacity represents the main problem of a reproducible reliable antiplasmin assay.


Canine cyclic haematopoiesis: marrow transplantation between littermates.

Dogs affected with cyclic haematopoiesis (CH) and experiencing recurrent 12-day cycles of neutropenia were supralethally irradiated and transplanted with marrow from their normal littermates. Following transplantation of the normal marrow, dogs with CH experienced no further cycles of neutropenia. Platelet and reticulocyte numbers also ceased to fluctuate cyclically in these dogs. The marrows of dogs with CH were transplanted into unaffected supralethally irradiated littermates. Prompt engraftment occurred in the recipient dogs with subsequent cyclic rises and falls of the numbers of platelets, reticulocytes and neutrophils. In the post-transplant period, immunosuppressant drugs were not used in three of the recipients and the fourth received only a single 5 mg dose of methotrexate.


Amino acid sequence studies on the alpha chain of human fibrinogen. Location of four plasmin attack points and a covalent cross-linking site.

The amino acid sequence of a 38-residue midsection piece of the alpha chain of human fibrinogen has been determined using a combination of plasmin-derived peptides and cyanogen bromide fragments. The segment contains several important features, including four early plasmin attack points, one of the two alpha-chain cross-linking acceptor sites, and a peptide homologous to one isolated from plasmin digests of bovine fibrinogen, and reported to have anticoagulant activity. The segment is sequentially adjacent to and overlapping with a large molecular weight (20000-25000) fragment released during plasminolysis. This latter material is very rich in glycine and serine and deficient in nonpolar amino acids. It also contains the other alpha-chain cross-linking acceptor site.