[X-ray diagnosis and surgical treatment of brain tumors in young children]. Among 319 patients under the age of three years with tumors of the brain verified by means of contrast X-ray examination, during operation, or on autopsy, 215 had undergone surgery (166 with tumor of the posterior cranial fossa and 84 with tumor of supratentotial localization). From analysis of 176 cases in which X-ray contrast methods of examination were applied it was established that the method is safe and yields sufficient information for making the topic diagnosis of the tumor, determining its blood supply, its relation to the system of the cerebrospinal fluid and for judging the degree of the concomitant internal hydrocephalus and occlusion of the cerebrospinal fluid passages. In addition, these methods help to solve problems of the techniques of surgical intervention or the contraindications for operations. Analysis of the results of 250 operations shows that when the child's condition and the localization of the tumor permit, the surgeon should strive to perform single-stage subtotal or total removal of the tumor because this does not increase postoperative mortality.


Adult human skin maintained in organ culture: I. The ultrastructure of the acellular compartment of connective tissue. Collagenolytic enzymes are produced by cultured skin explants. During cultivation the acellular compartment of the dermal connective tissues is digested away. The ultrastructure of the connective tissue resorption has been studied in human skin maintained in organ culture for 2--10 weeks. The connective tissue changes are: (1) Collagen fibrils with normal axial periodicity but decreasing diameters. On cross sections these fibrils have irregular outlines, while the longitudinal sections show fibrils separated into thin bundles of filaments 40--80 A thick with preserved normal axial periodicity. (2) Cross-banded filamentous aggregations (CBFA) consisting of fine parallel filaments 25 A thick and without axial periodicity. The CBFA has 350 A thick bands at 525 A intervals. At the end of the cultivation, the CBFA are replaced by solitary filaments 25 A thick. (3) The elastic fibres show no marked changes of the amorphous matrix, while the fibrils disappear. The loss of collagen and elastic fibrils during cultivation of the skin gives direct evidence of connective tissue degradation. The described changes are discussed in relation to previous ultrastructural studies on connective tissue resorption of various tissues.


Lipid droplets of the sebaceous gland: some new observations from tannic acid fixation. Electron microscopic examination using tannic acid fixation strongly supported the view that lipid droplets in the normal human sebaceous gland originate from smooth-surfaced endoplasmic reticulum. A true limiting membrane was clearly detected around the lipid droplets in the incipient stages but was undetectable in mature droplets.


[Does one have to be aggressive in the surgical management of diverticular disease of the colon (author's transl)]. A series of 61 consecutive cases with diverticular disease and its complications is presented. Fourteen cases with uncomplicated diverticular disease and 3 with massive GI tract hemorrhage underwent an uneventful (segmental) resection. Of 6 cases operated for fistula formation 1 died. Surgical therapy for abscessformation, peritonitis and "pseudo-tumoral" obstruction (38 cases) carried a high mortality (26.3%). The application of a one-staged aggressive and curative surgical approach lowers the mortality considerably, especially in the complicated forms of the disease. In a group of 30 cases so treated only 1 death occurred (3.3%). This in contrast with a group of 31 patients treated with a two-staged and initially palliative procedure with a mortality of 10 (32.2%). The Hartmann procedure with total excision of the lesion and avoidance of an enteroenteric anastomosis gives excellent results in the treatment of the complicated forms of the disease.


Ultrastructure of skin in primary systemic amyloidosis. Amyloid masses were found in the dermis of two brothers suffering from primary amyloidosis. The masses consisted of fibrils, composed in turn of twin hollow filaments of amyloid. An amyloid filament appeared as a 3 nm thick lucent core with a 2 nm thick wall. Occasionally 4--6 filaments were packed together in one fibril. The twin filaments were slightly twisted, with a twisting angle of 2.5 degrees and a coiling pitch of 1 160 nm. Wavy shapes of amyloid fibrils were also seen in elastic fibres. Amyloid fibrils were found in elastic fibres, under the basal lamina of the epidermis, sweat gland epithelium and Schwann cells; also around perineural cells, perivascular cells and, in one of the brothers, in collagen fibril bundles. No amyloid fibrils were found under the endothelial basal lamina. It would appear that amyloid fibrils are pathological fibrils belonging to the elastic fibre-basal lamina system.


Mast cells in solitary glomus tumors: a possible algogenic role. Mast cells in three cases of solitary glomus tumor were examined by light and electron microscopy. As seen by light microscopy, a number of round, oval or elongated mast cells were distributed throughout the stromal connective tissue and showed slight or moderate metachromasia when stained with toluidine blue (pH 4.1). Electron microscopy revealed various types and degrees of degranulation of mast cell granules, and also disclosed a close correlation between mast cells and non-myelinated nerve fibers. These findings suggest that mast cells may play an algogenic role in solitary glomus tumors, probably mediated by the contents, mainly histamine, concentrated in their granules.


Circulating immune complexes in lupus erythematosus, scleroderma and dermatomyositis. Circulating immune complexes (CIC) were measured by three different methods in serum from 17 patients with systemic lupus erythematosus (SLE), 3 patients with "hydralazine-induced" SLE-like syndromes, 14 patients with discoid lupus (DLE), 8 patients with systemic sclerosis and 5 patients with dermatomyositis. Immune complexes were detected in 13 of the 17 patients with SLE. All patients with lupus nephritis and typical exanthema had circulating immune complexes. The concentration of immune complexes was inversely correlated to serum complements C4 and C3. All 3 patients with "hydralazine-induced" SLE-like syndromes had circulating immune complexes that disappeared after withdrawal of the drug. Immune complexes were detected in 3 of the 14 patients with DLE; all 3 patients with CIC had wide-spread DLE. In systemic sclerosis, CIC were detected in only 1 of the 8 patients. Four of the 5 patients with dermatomyositis demonstrated CIC in serum. No complement consumption was detected in dermatomyositis and the immune complexes may have been secondary to tissue destruction.


Immunofluorescent and electron-microscope findings in the uninvolved skin of patients with systemic lupus erythematosus. Specimens of uninvolved skin of 20 patients with systemic lupus erythematosus (SLE) were studied using a direct immunofluorescent technique (IF) and the electron microscope (EM). EM examination revealed deposits of electron-dense material below the basal membrane, among collagen fibers in the dermis and in the walls of dermal blood vessels. The direct IF technique revealed granular "band" deposition of immunoglobulins and complement at the dermo-epidermal junction as well as granular deposition in the walls of blood vessels. There was close correlation between the IF and EM findings. It was concluded that the EM is of particular value in precisely delineating the location and ultrastructural pattern of skin deposits. The IF technique is not limited in relation to the size of area which can be studied and makes it possible to identify the specific immune fractions present. It is suggested that these two methods are mutually complementary in providing information concerning the deposition of immunoglobulins taking place in the uninvolved skin of SLE patients.


Effect of chloroquine on DNA synthesis in the skin of DLE patients. Changes in the semiconservative and excision repair DNA synthesis were studied autoradiographically in the skin of 12 patients with discoid lupus erythematosus during Chloroquine treatment (500 mg/day for 8 weeks). The originally increased rate of the semiconservative DNA synthesis in the area of the skin lesions returned to the normal level simultaneous with clinical improvement. No effect on the excision reapir DNA synthesis could be detected.


Neutrophil chemotaxis in psoriasis.

Neutrophil chemotaxis in psoriasis. Neutrophil chemotaxis was assessed in 69 psoriatic patients and 37 healthy human subjects. It was found to be significantly enhanced in 52 untreated patients. In 20 patients treated with an orally-administered phosphodiesterase inhibitor, Diphylline, neutrophil chemotaxis was normal. The enhanced chemotactic response of neutrophils from untreated patients with minimal skin lesions was at least equal to the response of those from patients with extensive skin lesions. Preincubation of normal human leukocytes with plasma derived from patients with widespread lesions markedly reduced their chemotactic activity. Plasma derived from patients with extensive skin lesions exhibited marked chemoattracting properties in comparison with plasma from healthy subjects. It is postulated that the basic intrinsic abnormality of neutrophil function in psoriasis could be caused by a decreased cyclic AMP/cyclic GMP ratio, similar to the decreased cyclic AMP/cyclic GMP ratio found in the lesional epidermis of this disease. Plasma factors which influence chemotaxis in psoriasis are related to the extent of the eruption and their effect is contrary to the effect of the basic intrinsic abnormality of psoriatic neutrophils.


In vitro lymphocyte transformation to nickel: a study of nickel-sensitive patients before and after epicutaneous and oral challenge with nickel. An in vitro lymphocyte transformation test (LTT) was performed in 8 patients with nickel contact dermatitis and in 4 control persons. The mitogenic response was of the same magnitude before patch testing, after patch testing and after oral challenge with nickel. When purified protein derivative (PPD) was used as the antigen, there was no difference between the LTT response of patients and controls before and after patch testing. After oral challenge with nickel, however, the patients' responses to PPD were significantly increased when compared with the responses after patch testing. The responses of the controls were unchanged. The LTT levels of the patients were approximately the same before and after patch testing, but were markedly increased after oral challenge.


Electron spin resonance studies on phaeomelanins. ESR spectra of synthetic melanins formed from dopa and from 5-S-cysteinyldopa and of melanins isolated from human melanomas were studied. Alkali-soluble melanin synthesized from cysteinyldopa showed a signal similar to that of insoluble melanin synthesized from dopa, but also a simple fine structure. Trichochromes C and F synthesized from 5-S-cysteinyldopa had a broader signal than dopamelanin, and in addition a hyperfine structure that could be explained by the presence of manganous ions. An insoluble eumelanin from a human melanoma with a sulphur content of 5% showed an ESR spectrum consisting of one line like dopamelanin. An alkali-soluble phaeomelanin from a human melanoma with a sulphur content of 10% showed a very broad signal with a hyperfine structure that could be explained by the presence of manganous ions.


Diffuse melanosis and trichochromuria in malignant melanoma. A previous finding of pronounced excretion of trichochromes in a patient with metastasizing melanoma and diffuse melanosis prompted this study on trichochromes in another patient with these two features. The patient now reported also excreted large amounts of trichochromes. Iit is suggested that diffuse melanosis in metastatic melanoma patients is due to deposition of trichochromes in the tissue.


Quantitation of skin bacteria: lethality of the wash solution used to remove bacteria. A widely used technique for the quantitative removal of bacteria from the skin uses a detergent, Triton X-100 (p, t-octylphenoxynonaethoxyethanol), to remove and suspend the bacteria. We determined the half-life for the survival of five common skin bacteria suspended in the solution. The shortest-lived was Streptococcus pyogenes with a half-life of 0.9 hours. All of the others (Propionibacterium acnes, Staphylococcus epidermidis, Staphylococcus aureus, and Klebsiella pneumoniae) had half-lives of 1.5 hours or longer. K. pneumoniae, the only Gram-negative species tested, had a half-life of more than 30 hours. Thus, a one hour delay in plating and incubation of samples suspended in this detergent solution inhibits quantitation of most species tested.


Linear dermo-epidermal IgA deposition in bullous pemphigoid. A case is reported of a patient with a bullous eruption with in vivo linear deposition of IgA and complement (C3) along the basement membrane zone of perilesional skin (DIF method). Some data presented here are in favour of the concept that cases of linear in vivo deposition of IgA alone, or in combination with other IF findings, might be classified as bullous pemphigoid (BP). Clearing of the lesions due to oral prednisone therapy was accompanied by disappearance of complement deposition, while IgA deposition remained unchanged. Some aspects of tissue injury in this case are briefly discussed.


Treatment of generalized scleroderma: updated results. Long-term treatment of patients with generalized progressive scleroderma by means of inhibitors of connective-tissue biosynthesis brings about total or subtotal regression of dermal sclerosis in 40.8%, partial regression in 33.1%, arrest of progression without regression in 14.8%, while in 11.3% it had no effect whatsoever. The drugs used were D-penicillamine, benzyl-penicillin-diethyl-aminoethylesterhydro-iodide, glutamine, hydralazine, chlorpromazine, L-dopa, diphenylhydantoin, and corticosteroids. Disease activity before, during and after treatment was indicated by the urinary fractions of high-molecular hydroxyproline and hydroxylysine containing peptides and of uronic acid, break-down products of collagen and acid glycosaminoglycans of connective-tissue ground substance. The prospects were better for young patients than for old, for those with a short history than for the longstanding disease cases, and for those having a large total dose than for those who had less. If left untreated, scleroderma progresses inexorably.


Severe skin pain after PUVA treatment.

Severe skin pain after PUVA treatment. Severe skin pain lasting one or two months occurred in 8 of 210 patients treated with PUVA. The pain started 4--8 weeks after the initial dose, mostly about one week after discontinuation of the treatment. It was a prickling, burning pain, usually coming in bouts and confined to limited areas "deep under the skin". In some respects the pain was related to itching, but the patients could easily distinguish between the two sensations. A variety of drugs was tried, but none had any noteworthy effect on this peculiar pain.


Pulmonary disease complicating intermittent methotrexate therapy of psoriasis. A patient with psoriasis was treated with methotrexate (MTX) orally once a week. Bilateral pulmonary infiltrations, hilar- and peripheral adenopathy with granulomas, cough, fever and dyspnoea developed after 10 months of treatment. Similar symptoms in patients receiving MTX have been described by others. The clinical symptoms cleared after MTX was withdrawn. However, the radiographic changes persisted long after the symptoms had resolved. The possibility of sarcoidosis incidentally developing during the MTX treatment is discussed.


Anti-androgen TSAA-291. I. Anti-androgenic effects of a new steroid TSAA-291 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one) and its derivatives. Anti-androgenic properties of newly synthesized steroidal compounds, TSAA-291 and its derivatives, were studied in the rat. (1) Subcutaneous administrations of TSAA-291 and TSAA-272 were effective in depressing the weight of seminal vesicles and ventral and dorsal prostates in the adult rat. (2) TSAA-291, TSAA-328 and TSAA-272 were shown to be anti-androgenic by the subcutaneous or oral route in the immature castrated male rat treated with testosterone propionate. The dose-response curves of all the test agents expressed in terms of percentage inhibition were approximately parallel to each other. Cyproterone acetate depressed the weight of levator ani muscle dose-dependently, whereas TSAA-291, TSAA-328 and TSAA-330 did not inhibit the muscle weight in a dose range sufficiently effective in inhibiting the weight of seminal vesicles and ventral and dorsal prostates. (3) TSAA-291 was also anti-androgenic against androstenedione and dehydroepiandrosterone. (4) Local administration of the anti-androgenic compounds into the left seminal vesicle or left testis of the young adult rat depressed the weight of the seminal vesicle or testis on the treated side as compared with the vehicle-injected contra-lateral side.


[Histological and histoenzymological study of liver. I: In gallstone without treatment (author's transl)]. 46 liver biopsies from gallstones and a control group have been studied by histological and histoenzymological technics. The most frequent injuries are in the portal tract, inflammatory infiltration and fibrosis; the most peculiar is a sinusoidal congestion. A brown pigment overload is seen in numerous livers. Lactic-, glyceric-, glutamic-, isocitric-, glucose-6-phosphate-deshydrogenase activities decrease but alkaline phosphatases-, transaminases activities are increased.


Histochemical distribution of acid mucopolysaccharides and some active transport enzymes in the lingual glands of Jaculus jaculus L. (Dipodidae, Mammalia). From examination of the structural data obtained for the tongue of rodent Jaculus jaculus, it has been possible to deduce that it is lined with filiform papillae in the dorsal epithelium and that it has a rich glandular apparatus consisting of anterior serous glands which are located immediately after the apex and composed of epithelial cells arranged in a single synctitial layer, and both nucous and seromucous acini (Weber's glands) in the posterior portion of the tongue on the lateral sides and ventromedian region respectively. In the tip glands there is an elaboration of protein material; both neutral and acid glycoproteins are absent. In the posterior Weber's glands acidic moieties in the mucosubstances are due mainly to sialomucins and hyaluronidase resistant sulfomucins; in the seromucous acini on the other hand, mucopolysaccharides with vicinal hydroxyl groups and proteins are present. The histoenzymological tests employed to detect the succinic dehydrogenase and carbonic anhydrase also revealed the two reactions in the seromucous acini. Their presence is discussed on the basis of their having a probable role in the salivary production mechanisms in the same way as those cells which have a very strong secretory activity, or those involved in ionic reabsorption processes. The role of granular catalase activity in the duct cells is assumed to be able of protecting the glandular parenchyma from bacterial attacks. The presence also of acid glycoproteins within the lingual glands is correlated with taste sensation in view of the current revaluation of the role played by the proteoglycans in neuronal functions.


A staining sequence for the differentiation of A-, B-, and D-cells of the islets of guinea-pig pancreas. Four mu sections of guinea-pig pancreas that had been fixed in Bouin's fluid were deparaffinized, hydrated, oxidized in equal volumes of 0.3% KMnO4 and 0.3%  H2SO4, decolorized in 2% oxalic acid and stained in 1% alcian blue in 70% alcohol for 10 min. Next they were stained for 5 min in chrome hematoxylin then into a dilute aqueous acid fuchsin solution followed by 2% phosphotungstic acid for 1 min. They were washed in running water until only the A-cells retained the red stain and were then counter stained with alcoholic aurantia for 5 min. Finally, the sections were cleared in xylene and mounted in D.P.X. Within the islets, B-cells stained blue green, A-cells bright red, D-cells pale yellow, while the acinar tissue stained blue grey. The wide separation between these colors represents a considerable advance on previous techniques for individual cell recognition within the islet.


[Combinations of enzyme-histochemical methods for differentiating of fibers types and evaluating the skeletal musculature (author's transl)]. This paper reports 2 combinations of enzyme-histochemical reactions (NADH tetrazolium oxidoreductase and myosin ATPase after alkaline preincubation, menadione-dependent glycerol-3-phosphate oxidoreductase and myosin ATPase after acid preincubation). One type of skeletal muscle fiber is stained golden-brown and the other blue. The differentiation of types of fibers is greatly improved by reliable classification. In addition, the same section can be used to determine the oxidative and glycolytic metabolic capacity, respectively. Finer differences in the structure of fibers may be recognized more easily and allowed of arrangement in a larger number of classes without dispensing with the old-established method of differentiating. It is possible for myopathological alterations to be made clearly visible. New and other combinations also offer promise of an advantageous extension of the method to other applications.


Ultrastructure of elastic fibers as shown by polarization optics after the topo-optical permanganate-bisulfite-toluidine blue (PBT) reaction. Permanganate-bisulfite-toluidine blue (PBT) reaction proved to be a highly selective and sensitive method for demonstration of elastic structures in tissue sections. Permanganate oxidation liberates a great amount of aldehyde groups in young and adult elastic fibers both in bovine ligamentum nuchae which can be demonstrated with the bisulfite-toluidine blue (pH = 1.0) staining procedure. There are suggestive evidences that the aldehyde groups are liberated from the desmosine and isodesmosine cross bondings of elastin. The dichroism and the strong birefringence of the elastic fibers induced by the PBT reaction indicate a high degree of linear fibrillar molecular order of the reacting elastin molecules which are assumed to be arranged helically in the aortic elastic fibers and they are assumed to show 2 different micellar textures in ligamentum nuchae fibers as reported with other topo-optical reactions earlier by Romhanyi.


Peritoneal macrophages introduced into mouse foot pads enter the germinal center of regional lymph nodes nonspecifically. Male mice were injected into their foot pads with sheep erythrocytes (SRBC) to form lymph follicles in the germinal centers in the popliteal lymph nodes. 4 weeks later, peritoneal macrophages labeled with carbon from syngeneic donors sensitized with SRBC or typhoid-paratyphoid bacilli (TAB) were separately injected into the foot pads as well. The popliteal lymph nodes were histologically examined at 6 h to 5 days after injection. Labeled macrophages appeared in the marginal sinus, migrated straight across the cortex from the marginal sinus to the lymph follicles and then entered the germinal centers. There was no difference in the mode of appearance, migration and localization of labeled macrophages in the regional lymph nodes between the mice given labeled macrophages from SRBC-sensitized donors and those given macrophages from TAB-sensitized donors. The entrance of lymph macrophages into the germinal centers of the regional lymph nodes would be immunologically nonspecific. After the injection of Pelikan ink into the foot pads, the macrophages which have taken up carbon in the peripheral tissue reached the regional lymph nodes via the afferent lymphatics and then entered the germinal centers, mainly through the medullary pole of the lymph follicles, after migrating along their immediate exterior from their marginal sinus to their medullary pole.


Histology and mucosubstance histochemistry of ferret lingual glands. The histology and mucosubstance histochemistry of the ferret lingual glands were studied. Both serous and mucous minor salivary glands were present in the posterior part of the tongue. In serous glands, acinar cells and a very few cells of the excretory ducts contained granules which gave reactions for neutral mucopolysaccharides only. The mucous glands, including the duct system, contained mainly weakly sulphated acidic mucin, some neutral mucin but no carboxylated mucin. Occasional goblet cells were present in the excretory ducts of both serous and mucous glands. They contained weakly sulphated mucin.


Argentophil neuronal perikarya and neurofibrils induced by postmortem trauma and hypertonic perfusates. Argentophil neuronal perikarya and perikaryal neurofibrils similar to those illustrated in Ramón y Cajal's classical studies have in the present investigation been found to be manifestations of the chromophil neuron. Conclusive evidence of such association was obtained by silver impregnation with the Bodian technique of sections previously stained with cresyl violet. Regardless of the fixative used, silver-impregnated neurofibrils were evident when (1) normal tissues were fixed by immersion or unsuccessfully fixed by perfusion, (2) normal tissues were exposed and touched after death but before perfusion with the fixative, or (3) flow of perfusates was compromised by the effect of an experimental procedure, as well as when (4) a hypertonic saline solution was used in the first perfusate. These cytologic peculiarities were still discernible after 24 h of postmortem autolysis following a delay in removal of the brain or in immersion of the exposed brain in the fixative. After immersion fixation, argentophilia and chromophilia occurred ubiquitously in the brain of the newborn guinea pig; however, argentophil neurofibrils were noted in the absence of chromophil neurons in the brain stem of the newborn rat, rabbit and cat. After fixation by perfusion, perikaryal neurofibrils were not impregnated in either newborn or old animals or in animals with facial nerve transection. Affinity for Congo red or birefringency, exhibited by neurons with marked neurofilbrillary changes in human senile brain atrophy, were absent in the present material. On the basis of the current light-microscopic observations, it is concluded that argentophilia of neuronal perikarya and perikaryal neurofibrils is another manifestation of the chromophil neuron induced by postmortem trauma and of the ocellate neuron elicited by perfusion with hypertonic saline.


A neuropathologic study of Whipple's disease. A patient with Whipple's disease developed massive and irreversible CNS involvement after a drug-induced intestinal remission. The multifocal brain lesions were apparent grossly with the heaviest concentration being noted in rhinencephalon, diencephalon, and mesencephalon. This patient exhibited progressive neurologic deterioration, although viable organisms could not be identified in the brain at autopsy. Astrocytes, pericytes, and choroid plexus cells attempted to dispose of the organism, in additional to the traditionally implicated microglial and ependymal cell.


Organ cultured donor material for penetrating corneal grafts. A preliminary report. Fresh and undamaged cornea had unchanged endothelial cell density for four weeks in culture, while eyes removed at autopsy suffered a cell loss. Acceptable cell density was found in eyes removed within eight hours, and this was confirmed by the results of 55 penetrating grafts using cultured autopsy material. Storage in culture for more than one week seemed to influence the results unfavourably. Immune reactions were not seen.


Refsum's disease. Eye manifestations in a patient treated with low phytol low phytanic acid diet. The cardinal eye symptoms of Refsum's disease are night blindness, retinal pigmentary degeneration and constriction of the visual fields. Similarities with or differences from retinitis pigmentosa are discussed. A 39-year-old male has had manifestations of Refsum's disease from the age of 7 years and has been on a low phytol low phytanic acid diet for the last 13 years. Peripheral ring scotomas were present. Some reduction of the visual fields has been recorded, but only in the far periphery. The central field has not been significantly constricted during a 7-year period. Very good visual functions were found within this area. All cone mechanisms were functioning at a normal level. A moderately reduced sensitivity level of the rod mechanism could be explained in a great measure by poor pupillary dilation in the dark. In this patient minimal or no progression of the visual findings was apparent. Probably an effect of treatment, there is little resemblance with ordinary retinitis pigmentosa. ERG showed moderate abnormality. Normal conducting time was found by VER. With fluorescein angiography a central area of normal appearance was sharply outlined in contrast to marked degenerations in paracentral regions.


Beta-2-microglobulin, an indicator of renal tubular maturation and dysfunction in the newborn. The urinary excretion and proximal tubular reabsorption of beta-2-microglobulin was studied in 17 healthy newborn infants in relation to gestational and post-natal age. The effect of IRDS and non-conjugated hyperbilirubinemia on the tubular reabsorption of the protein was evaluated in 10 IRDS infants and 14 infants with non-conjugated hyperbilirubinemia. The urinary excretion of beta-2-microglobulin was determined under standardized conditions. When GFR was determined, the single injection clearance method was used. The filtered load of beta-2-microglobulin was found to increase with increasing gestational age. This was due to a rise in plasma beta-2-microglobulin concentration as well as to a rise in the GFR. Although the smallest filtered load was recorded in infants with a mean GA of 32.4 weeks, these infants had a lower fractional reabsorption of the protein (88%) than infants with a mean GA of 35.0 weeks or more (98%). In infants with a GA of 35 weeks or more a glomerulo-tubular balance for beta-2-microglobulin apparently was established. In these infants the filtered load of beta-2-microglobulin increased rapidly during the first days of life. This was paralleled by an increase in the reabsorptive capacity for the protein. In infants with IRDS and in infants with non-conjugated hyperbilirubinemia the fractional reabsorption of beta-2-microglobulin was lower than in control infants of a corresponding gestational and postnatal age. This indicates, that in the neonatal period, the proximal tubular transporting capacity is more vulnerable than the glomerular filtration rate in states of hypoxia and hyperbilirubinemia.


Amyloid-like green birefringence in cytoskeletal 10 nm filaments after staining with Congo red. The commonly accepted markers for amyliod are a fibrillar ultrastructure and congophilia combined with green birefringence when viewed under polarized light. Although a number of cells have been implicated in amyloid formation the detailed events leading to accumulation of amyloid are still unknown. Previous studies have suggested that amyloid shares antigenic properties with cytoskeletal intermediate (10 nm) filaments and connective tissue microfibrils. In the present study we show that such filaments present in fibroblasts and lymphoid cells have an affinity for Congo red, exhibit the typical green birefringence and are ultrastructurally indistinguishable from amyloid fibrils. Intermediate filaments of cultured fibroblasts depleted of nutrient medium retained the Congo red birefringent property and typical ultrastructure despite cell damage. Our observations suggest that amyloid deposits may form locally through abnormal accumulation of bundles of cytoskeletal intermediate filaments under conditions characterized by increased cell proliferation and death.


The diagnostic value of cytochemical staining for non-specific esterase in the search for cancer cells in effusions. 143 consecutive effusion samples were stained for non-specific esterase (NSE) in order to test the diagnostic value of the staining method with reference to the diagnosis of carcinosis in pleural and peritoneal cavities. On comparing the results obtained by cytomorphological evaluation and NSE staining the former was proved to have a signficnat higher diagnostic specificity. The diagnostic sensitivity of the two methods showed no difference. The low diagnostic specificity of the NSE staining was due to occasionally intense staining of macrophages and mesothelial cells in connection with reactive states of the mesothelium. The NSE staining is not recommendable as a diagnostic supplement to the cytomorphological evaluation.


Formation of granulation tissue in subcutaneously implanted sponges in rats. A comparison between granulation tissue developed in viscose cellulose sponges (Visella) and in polyvinyl alcohol sponges (Ivalon). A comparison was made between the granulation tissue formation in two different synthetic sponge types. Visella and Ivalon, of different sizes. The granulation tissue formed in the two sponge types did not differ qualitatively, and had the character of wound tissue and inflammatory tissue in man. The rate of tissue formation in the Visella sponges was faster and the tissue was more homogenous than in the Ivalon sponges. Fourteen-day-old Visella implants of either size contained more granulation tissue than Ivalon sponges, probably owing to the smaller pore size of the former material. This may also account for the more frequent occurrence of giant cells in the Visella implants. In contrast to the Visella sponges, the trabeculae of the Ivalon polymer showed calcification and positive staining properties with histological staining procedures, and deformation was frequent among the Ivalon implants. Thin sponges of either type closed in about 21 days, thick ones after about 42 days of implantation. Calculated per 2 cm3 of implant, thin sponges produced more tissue after 14 days of implantation than thick noes. It is concluded that the Visella sponge type is best suitable for this experimental model of inflammation.


The anal transitional zone. Location and extent. The location and extent of the anal transitional zone (ATZ) were investigated in the age group typical for anal canal carcinomas. The methods used were macroscopic determination after whole-mount staining with Alcian-dyes as well as conventional histological technique. The results show that the epithelial variants may be found over a larger area than previously reported, namely from 6 mm below to 20 mm above the dentate line. Variations in location and extent of the ATZ are described, as well as the frequent finding of mature squamous epithelium high in the anal canal. The significance of the findings in relation to the special types of anal canal carcinomas is discussed, and on the basis of the macroscopic definition of the canal, as well as the histological observations in this study, it is proposed that anal canal carcinomas should be defined as tumours partly or totally located within a distance of 2 cm above the dentate line.


Antibodies to the strain-specific and cross-reactive determinants of the haemagglutinin of influenza H3N2 viruses. 1. Preparation of antibodies and in vitro studies. The serological analysis of antibodies to the haemagglutinin (HA) of influenza A viruses of the Hong Kong (H3N2) subtype is described, using haemagglutination-inhibition, immuno-double-diffusion and single-radial-diffusion techniques. By cross-absorption of antisera to purified HA antigens, different populations of antibody molecules were obtained, which are designated strain-specific and cross-reactive and characterized in terms of their antigenic specificities for HA antigens of the homologous and antigenically variant H3N2 viruses. A narrowly strain-specific population of antibodies (SS"HK) was obtained as the residual antibody in antiserum to A/Hong Kong/1/68 HA after absorption with the closely related A/England/42/72 virus, whilst a contrasting broadly cross-reactive population (CR'HK) was obtained by absorption of the anti-A/Hong Kong/1/68 HA serum with the more distantly related strain A/Victoria/3/75 and eluting the cross-reactive antibodies from the absorbing virus. Similarly, specific and cross-reactive antibodies were derived from antiserum to A/Victoria/3/75 HA antigen by absorption with A/Hong Kong/1/68 virus. Single-radial-diffusion tests were performed, involving sequential application of different antibody preparations in the same wells in immunoplates containing intact virus particles. The cross-reactive and strain-specific antibodies differed in their property of mutual interference of attachment ot antigen. The results suggested that the cross-reactive antigenic determinants on the HA subunit may be located closer to the distal end of the molecule than the strain-specific determinants. Further tests employing single-radial-diffusion showed that there are more cross-reactive than strain-specific sites available for antibody in the intact virus particle. The strain-specific antibodies also gave higher haemagglutination-inhibition titres per microgram IgG than the cross-reactive antibodies.


Fibrinogen binding structures in beta-hemolytic streptococci group A, C, and G. Comparisons with receptors for IgG and aggregated beta 2-microglobulin. Binding of radiolabelled fibrinogen was measured to 197 strains of 16 different bacterial species. All streptococcal strains belonging to groups A, C, and G isolated from human sources were strongly positive. S. aureus strains showed low binding values. Occasional group B streptococci were positive. Reactive strains were also noted among group C streptococci of animal origin, Streptococcus zooepidemicus and Str. equii, and bovine beta-hemolytic group G streptococci. Bovine alpha-hemolytic group G strains as well as the remaining seven species of human origin were all negative. Inhibition experiments and correlation studies indicated that the streptococcal receptor for fibrinogen was different from immunoglobulin Fc binding reactivity. Comparisons with the newly discovered beta 2-microglobulin binding factor showed that trypsin concentrations which destroyed this receptor left the fibrinogen receptor intact. Although the two receptors correlate in strain population studies and show competition for binding the difference in trypsin sensitivity indicates that they represent two different structural entities. Both receptors might serve as basic markers for M-protein like surface components of Gram positive cocci.


Influence of contrast media osmolality on isolated rabbit heart performance. A low osmolality contrast medium (Iopamidol) caused less cardiac disturbance on isolated rabbit heart than a high osmolality medium (Urografin). The same effects were induced by glucose solutions iso-osmolal with the two media. After perfusion with Propranolol (1 microgram/ml) and Cimetidine (1 microgram/ml) the observed effect was unaltered.


Tamoxifen treatment of advanced breast carcinoma. Sixty postmenopausal patients with microscopically confirmed, progressive mammary carcinoma and local recurrence alone or in combination with distant metastases or with distant metastases only, not previously treated with cytostatics, were given tamoxifen (Nolvadex), 10 mg 3 times daily. The response rate in 37 evaluable patients was 48 per cent, with a median duration of the response of 26+ weeks. The effectiveness of the drug increased significantly with an increasing interval between primary treatment and the appearance of the first recurrence. No serious side effects occurred.


Home observation for measurement of the environment: a revision of the preschool scale. Information pertaining to a revision of the Caldwell HOME Inventory for use with families of children ages 3 to 6 was presented. Factor and item analyses were used as a basis for reducing the number of items from 80 to 55. The items were clustered into eight subscales. Kuder-Richardson 20 coefficients for the scale ranged from .53 to .93. Concurrent and predictive validity studies indicated that the HOME scales significantly correlated with IQ (as high as r = .58). Low to moderate correlations were obtained between HOME scores and SES measures, with significant correlations ranging from .30 to .65.


Yolk sac tumor of the anterior mediastinum. Case report with light- and electron-microscopic examination and immunohistochemical study of alpha-fetoprotein. A case of yolk sac tumor of the anterior mediastinum was studied by light and electron microscopy and found to have characteristic patterns which were similar to a neoplasm of gonadal origin. These findings, in addition to the immunohistochemical identification of alpha-fetoprotein in the tumor, indicated that the neoplasm was germ cell in origin. A brief review of previously reported cases is included. Prognosis of the patients with yolk sac tumor of the anterior mediastinum was generally dismal; however, those patients with tumors incidentally found but completely excised survived without evidence of reucrrence.


Distribution of wheat germ agglutinin binding sites on normal human and guinea pig bone marrow cells: an ultrastructural histochemical study. The wheat germ agglutinin-gold labeled ovomucoid (WGA-Ovo-G) method has been employed in the ultrastructural localization of WGA surface receptor sites on gluteraldehyde-fixed normal human and guinea pig bone marrow cells. The number of gold particles per micron of cell surface were counted and data subjected to statistical analysis. WGA labeling of the bone marrow cells was found to be quite heavy and evenly distributed along the cell surface. Only macrophages, in both species, and a number of lymphocytes in the guinea pig exhibited limited WGA labeling. Comparison of morphologically similar cell types in human and guinea pig marrow indicated that WGA receptor sites were more abundant on the guinea pig hemic cells. WGA surface labeling was found to be not only related to cell type and to animal species but, in some instances, varied with the stage of maturation of a given cell line; viz., neutrophilic cell series in both man and guinea pig and erythrocytic cell series in the guinea pig.


[In vitro influence of albumin, gammaglobulin and fibrinogen on the sedimentation rate and the rheological behaviour of the red cell (author's transl)]. The complexity of the mechanisms which enter into play in the phenomenon of erythrocyte sedimentation have for long aroused the curiosity of research workers. A simultaneous study of this parameter and of the viscosity, of the relative zeta potential together with the osmotic fragility, led us to appreciate the respective actions of three isolated plasma proteins  : albumin, immunoglobuin G, fibrinogen, on the ESR and on the rheological properties of the red cell.


Antigenic structure and relationship between serotypes 1 and 2 of Haemophilus paragallinarum. Antigenic structure and relationship between serotypes 1 and 2 of Haemophilus paragallinarum were analyzed by the rapid plate agglutination and cross-absorption tests. Encapsulated strain forming iridescent colony type of both serotypes 1 and 2 had at least three antigens: heat-labile and trypsin-sensitive (L), heat-labile and trypsin-resistant (HL), and heat-stable and trypsin-resistant (HS). The L was a major antigen located in a surface and divided serologically into three parts: L1, L2, and L3. The L1 was specifici to serotype 1, the L2 was specific to serotype 2, and the L3 was a common antigen shared by serotypes 1 and 2. The HL and HS were common antigens between serotypes. By trypsinization or heating at 121 C, L antigen lost its agglutinability and agglutinin-producing ability. Nonencapsulated organisms forming noniridescent colony type lacked the L antigen. These results suggested that antigenic structure of H paragallinarum serotypes 1 was L1, L3, HL and HS, while serotype 2 was L2, L3, HL, and HS.


Relationship of seminal volume to size and disease of the prostate in the beagle. The seminal volume of young adult Beagles was correlated with the size of and disease in their prostates. The ejaculate volume of naturally collected semen increased in a linear manner with prostatic weight in dogs with normal or glandular hyperplastic prostates. This correlation was not observed in the dogs with cystic hyperplasia, in which there was a reduction in volume of 50% in the semen produced for each gram of prostate. There were no significant differences in other seminal characteristics regardless of prostatic size of disease.


Effect of azacytidine on Simian Virus 40 nucleoprotein complexes. Simian virus 40 nucleoprotein complexes synthesized in the presence of 5-azacytidine showed small differences in sedimentation rate on neutral sucrose and buoyant density in metrizamide and cesium chloride. Simian virus 40 deoxyribonucleic acid (DNA) I, isolated from the nucleoprotein complexes of drug-treated cultures, was found to band at a higher buoyant density and therefore had a decreased ability to bind ethidium bromide. The data indicated that these molecules were deficient in superhelical turns. Treatment with 5-azacytidine was shown to inhibit protein synthesis, which preceded the inhibition of DNA synthesis. Under the same conditions, protein synthesis was inhibited to a greater degree and occurred much faster than inhibition of DNA syntheses. Upon removal of the drug, resumption of protein and DNA synthesis occurred slowly. It is concluded that the inhibition of simian virus 40 DNA synthesis and the conformational alterations in DNA I isolated from nucleoprotein complexes result from the inhibition of protein synthesis.


In vitro production of Rauscher murine leukemia virus: influence of culture age on biological properties. Large-scale production and concentration procedures have been standardized to study the biological properties of Rauscher leukemia virus produced from the high-passaged JLS-V9-H mouse bone marrow cell line. Virus produced early (days 4 to 6) in the harvest and refeed cycle contained higher levels of ribonucleic acid-directed deoxyribonucleic acid polymerase activity and was more infectious than Rauscher leukemia virus produced later (days 7 to 10) in the growth period. The peak of virus production as detected by physical assays (virus particle count, protein, and p30 antigen) was highest at day 6, whereas the optimum biological and ribonucleic acid-directed deoxyribonucleic acid polymerase activity occurred 24 h earlier. When product characterization values of each concentrate were adjusted to a specific activity (i.e., per milligram of protein) basis, virus particle counts averaged 4 x 10(11) through days 5 to 9, and the peak infectivity occurred at day 4, whereas ribonucleic acid-directed deoxyribonucleic acid polymerase activity was highest at day 4 (endogenous) and 5 (exogenous). Sodium dodecyl sulfate-polyacrylamide gel analysis revealed only slight differences in the polypeptide pattern of Rauscher leukemia virus harvested from cultures of varying age, although Rauscher leukemia virus produced between days 3 and 5 contained more glycoprotein than either earlier or later harvests.


[The LE cell phenomenon. New aspects in molecular biology and immunocytology]. 1. The effects of antinuclear antibodies on nuclear material can be observed directly in free leucocyte nuclei in the supravital preparation according to Engel. 2. The antinuclear antibodies prevent the lysis of free nuclei, they obstruct the normal degeneration of nuclei. 3. The nuclear blockade is recognizable in the dark-clodded, rigid nuclei which remain small. These blocked nuclei are the visible expression of a development of complexes between chromatin and antinuclear antibodies. 4. It is supposed that the protective effect of antinuclear antibodies consists of the obstruction of the DNases and histon-proteases bound to chromatin. 5. The effects of antinuclear antibodies is in agreement with the structure of the nucleosomes of chromatin. 6. The nuclear blockade caused a persistence of antigenic material, which can create an increase of antibody production. This means that in vivo the antinuclear blockade is an effect which sustains illness.


[Histamine levels in interstitial fluid of lesional and perilesional skin in patients with chronic idiopathic urticaria (author's transl)]. In 8 patients with idiopathic chronic urticaria suction blisters were produced simultaneously on lesional and perilesional skin in the periumbilical area without application of heat. The suction pressure was 250 mm Hg, and thus the blister production lasted from 60--120 min. The blister fluid histamine was determined with a modified autoanalyzer technique developed by Siraganian. In this method the extractionof histamine, the condensation of o-phthaldial-dehyde with histamine and the measurement of the fluorochrome is automated. With the described method it is possible to measure values less than 0.5 ng/ml. Histamine levels in perilesional skin were nearly in the same range as in the periumbilical skin of 10 normal persons. The range of the normal tissue fluid histamine levels was 0--15 ng/ml and they did not differ significantly from the plasma levels. In all 8 patients with chronic urticaria the histamine values were higher in lesional than in perilesional skin. In 1 patient the lesional blister fluid histamine value reached 35.5 ng/ml. Four of the patients showed only low differences (less than 3 ng/ml).


[Effect of pH on the motility of isolated jejunal loops in dogs]. Thirty-Vella jejunal loops are perfused at a constant rate with solutions of variable pH (1.55-11.25). Net loop absorption and motility of the oral segment do not significantly vary between pH values of 2.2 to 10.0. At a more acid pH, there exists a strong increase in the amplitude of pressure waves accompanied by a decrease in their frequence.


Energy-dependent accumulation of Ca2+ by human embryonic lung fibroblasts. Human embryonic fibroblasts accumulate Ca2+ in the presence of extracellular ATP and Mg2+, the uptake being maximal at 3 mM ATP. Iodoacetic acid, oligomycin and temperatures of 2 degrees C all inhibit the ATP-potentiated uptake suggesting that an active process may be involved in the transport of Ca2+ into these cells under certain conditions.


Inhibition of energy-dependent Ca2+ accumulation in fibroblasts by smooth muscle antibodies. An antibody prepared against smooth muscle myosin interferes with active Ca2+ accumulation of fibroblasts. This provides further evidence for the existence of myosin at the cell surface.


Variations of cyclic AMP and cyclic GMP contents of the liver and of brown and white adipose tissues of the rat during the first week of cold exposure. The variation in the amounts of cyclic AMP and cyclic GMP were studied in white and brown adipose tissues and in the liver of rats during the first week of cold exposure (5 degrees C). In white fat, only a small increase in cAMP was observed on the first day. In brown fat, parallel decreases in cAMP and cGMP contents were induced which might be related to a large mobilization of tissue fatty acids. In the liver, cold exposure barely affected the cAMP content but the level of cGMP was markedly increased. These results are discussed with regard to the respective role of these different tissues in cold-induced energetic substrate mobilization.


[Lipovitellins in Palaemon adspersus (Rathke, 1837)]. The study of the ovarian cycle of Palaemon adspersus shows the occurrence of two lipo-glycoproteins accumulated into the ovocytes during vitellogenesis. The molecular weight of the main protein constituent in vitellus is evaluated to about 350 000 daltons. This protein is formed by two subunits having a similar molecular weight. The incorporation in vitro of [14C] leucine shows the participation of the ovary to lipovitellin synthesis.


Changes in the fatty acid composition of Drosophila melanogaster during development and ageing. In Drosophila melanogaster the saturated fatty acids increase in amount early in pupal development relative to the concentrations in late third instar larvae, then decline to the levels characteristic of one-day-old adults. Conversely, the monounsaturated fatty acids decline in content early in pupal development, then increase late in the pupal period. Lauric acid (12:0), myristic acid (14:0) and palmitoleic acid (16:1) become more prominent and oleic acid (18:1) and palmitic acid (16:0) less prominent as the adult ages. At about 40 days of adult age myristic acid (14:0) begins to decrease and oleic acid (18:1) to increase. Within 20 days of eclosion males and females contain different amounts of myristic acid (14:0), palmitic acid (16:0) and oleic acid (18:1).


The interaction of lanthanides with isolated sarcoplasmic reticulum vesicles from rabbit skeletal muscle. The interaction of lanthanides with isolated sarcoplasmic reticulum (SR) vesicles from rabbit skeletal muscle and the effects of lanthanides on 45Ca2+ uptake by the vesicles were studied. 153Gd3+ was taken up by the vesicles in the absence of ATP and oxalate in a time-dependent manner, reaching a maximum total accumulation of 380 nmol 153Gd3+/mg protein after 20 min with 200 microM 153Gd3+. This 153Gd3+ accumulation was not washed out by 1 mM EGTA. The addition of ATP induced the release of 87% of the bound 153Gd3+, leaving behind irreversibly-accumulated 153Gd3+. Pre-incubation of the vesicles with lanthanides in the absence of ATP and oxalate inhibited 45Ca2+ uptake without affecting Ca2+-ATPase activity. The percent inhibition of 45Ca2+ uptake increased with length of pre-incubation of the vesicles with lanthanides, reaching 33% after 20 min of pre-incubation. Increasing the 45Ca2+ concentration or adding ATP or oxalate to the preincubation medium abolished these inhibitory effects on 45Ca2+ uptake.


Inactivation of the slow potassium outward current in crab muscle fibre. The slow outward current (IK2) recorded in crab muscle fibre using the double sucrose gap method decreases when high and maintained depolarizations are applied. This decrease corresponds to a true inactivation of the potassium conductance rather than to a shift in the reversal potential of the charge carrying ion following local accumulation.


[Changes in blood levels of noradrenaline in man following short and long term exogenous infusion]. Norepinephrine (NE) was infused in four normal men in doses of 1.5, 6.0 and 9.0 microgram/min for 60 min. The rise in plasma NE was observed only after 5 min and steady state plasma NE and infusion rates. The calculated turnover time averaged 35 sec for 1.5 microgram/min infusion and 20 sec for both 6.0 and 9.0 microgram/min infusion experiments. These differences may be explained by adjustments occurring in inactivation processes in relation to infused doses. A basal endogenous overflow rate of 15 ng kg-1 min-1 was calculated for NE. In the month following NE infusion plasma concentrations decreased exponentially but remained above preinfusion values during about 10 days. The above results confirm the important role of inactivation mechanisms to remove NE from plasma and show that the amine taken up by sympathetic neurons may be released over a long period following the end of infusion.


Dipyridamole affects myocardial adenosine kinase activity. Adenosine kinase (EN 2.7.1.20) from rat and dog heart was purified until it was devoid of adenosine deaminase activity. A stimulation of adenosine kinase activity by dipyridamole was observed when the enzyme was assayed under optimal conditions. At low substrate concentrations adenosine kinase was inhibited by the drug. It increased the Km for adenosine sevenfold. The effects of dipyridamole were Mg2+-dependent. The adenosine-sparing action of dipyridamole at low substrate concentrations is in keeping with the vasodilatory action of the drug.


[Effect of noradrenaline on its own internal liberation from cortex synaptosomes in the rat]. Norepinephrine (NE) uptake velocity in rat cerebral cortex synaptosomes does not depend on internal NE contents: continuous exchange occurs. NE enhances spontaneous release and inhibits release elicited by KCl. Phenylephrine an a agonist, produces the same effect. Phentolamine, an a antagonist, did not modified the spontaneous release but enhanced release elicited by KCl 25 mM.


Cortisol-binding components of cytosol receptor in normal and adrenalectomized rat liver. [3H] cortisol was found to be bound to two distinct components of receptor protein in hepatic cytosol of both normal and adrenalectomized adult male rats. In liver cytosol of normal rats, 78% of total bound [3H] cortisol to receptor was associated with the first receptor component, and about 20% to the second one. However, the first component of cytosol receptor in adrenalectomized rats was found to bind 95% of total [3H] cortisol bound to both receptor components, while only 4.5% of the bound hormone was found associated with the second receptor component. These alterations in binding capacity are discussed in relation to possible regulation of nuclear RNA synthesis by cortisol-receptor complexes.


Hormonal regulation of osmotic and ionic balance in the haemolymph of the larvae of dragonfly, Aeschna cyanea (Müller) (Odonata : Aeschnidae). The present studies provide an evidence of an active involvement of the neurosecretory A cells of the thoracic ganglia in both, the internal hypo- and hyperosmotic regulation in the larvae of Aeschna cyanea.


[Effect of the modality of exercise on the VO2 max]. 1. Maximum oxygen consumption has been measured by means of three different exercises: cycle ergometry, treadmill running and uphill walking with a 20 kg-load. 2. Loaded walking allowed to reach a VO2 max level in average 2% greater than running and 13% greater than bicycling. 3. This finding suggest that VO2 max may depend on peripheral factors.


[Intravenous perfusion of adrenaline and adaptation to muscular exercise in man]. Eleven normal subjects underwent epinephrine perfusions (1.9; 6.1; 11.8 ng/min) during a short (20 min) and mild (50% VO2 max) exercise. VO2 was not modified by epinephrine perfusion, while heart rate ventrilation and plasmatic lactate were increased proportionally to epinephrine doses.


Column chromatography of plant polyphenols on weak anion exchangers. Mixtures of phenols and cinnamic acid derived plant polyphenols are separated on several WAX cellulose materials and on DEAE Sephadex. Reference mixtures are also split up into the following distinct groups: phenolic carboxylic acids--neutral o-dihydroxy phenolics--neutral non o-dihydroxy phenolics. Quantitative recoveries are obtained, while no isomerizations occur with the pH labile plant phenolics. It is suggested that these materials can be used for preparative scale purification of plant phenolics, or for cleaning up plant extracts prior to HPLC examination.


Species differences in the chronotropic response to acid-base alterations. The chronotropic response to acid-base alterations was studied in isolated spontaneously beating atria of rat, cat and rabbit. In the three species, atrial rate was found to be dependent on extracellular pH. Both "respiratory" and "metabolic" alterations affected chronotropism to the same extent. Decreasing pH from 7.8 led to a decrease in rate in the three species, although the rabbit kept atrial rate constant when pH changed between 7.65 and 7.18. There was a curvilinear relationship between rate and pH so that decreasing pH from 7.8 to 7.4 had a lesser chronotropic effect than decreasing pH below 7.4. However, when atrial rate was plotted against hydrogen ion concentration, an almost linear relationship was obtained. Species differences were observed when assessing the absolute decrease of atrial rate for a given change in pH. The rat was the most responsive of the species tested, while the rabbit possessed the least ability to change its rate in response to modifications in pH.


[Effect of natural amino acids on ethanol oxidation in isolated rat hepatocytes]. The effects of the various naturally occurring amino acids on ethanol oxidation in hepatocytes from starved rats was systematically studied. In order to minimize the non ADH pathways, the ethanol concentration used was 4 mmol/litre, the amino acids being added at the same concentration. In hepatocytes from fasted rats, alanine, arginine, asparagine, aspartate, citrulline, cysteine, glutamate, glutamine, glycine, histidine, hydroxyproline, ornithine and serine increase significantly ethanol consumption. The stimulatory effect of glutamine being much less pronounced than the asparagine one and proline being devoid of action, the influence of ammonium chloride addition on ethanol consumption in the presence of these amino acids was studied. Ammonium chloride determines an enhancement of ethanol oxidation in these conditions, the results showing no apparent correlation between intracellular glutamate concentration and ethanol oxidation rate, contrarily to previous data. In hepatocytes from fed rats, only alanine, asparagine, cysteine, glycine, hydroxyproline, ornithine and serine increase ethanol oxidation, although to a lesser extent than in cells from starved rats.


[Echovirus encephalitis during Bruton disease. Favorable development. Therapeutic problems]. A 16 year old boy with Bruton type agammaglobulinaemia developed acute encephalitis. Echo virus type 3 was isolated on two occasions from the same sample of CSF. Clinical improvement occured after treatment with gammaglobulin with high anti-Echo virus titers given intramuscularly and intrathecally. However the C.S.F. protein is still raised so that it is not certain he has been completely cured.


[Unusual pseudosarcoid granulomatosis of a prostatic adenoma]. In the reported observation, numerous granulomas of the sarcoid type in the absence of sarcoidosis were found under the capsule of the removed prostate adenoma in a man of 57 who was practically normal for 8 1/2 years after the operation. Some of these granulomas were formed around adenoma glands. Also, large periglandular lymphoidcell infiltrates were found, sometimes with foci of cells similar to epithelioid ones. It is assumed that these infiltrates may precede granuloma formation. In the same sections there were rounded foci of sclerotic changes which apparently may be due to scarring of granulomas. An infectious-allergic genesis of the disease is suggested.


[Nature and origin of hepatocellular hyaline, Mallory bodies]. The current concepts on the nature and origin of alcohol hyaline are analysed. The latter is a sign of acute alcoholic hepatitis and reflects the severity of destructive and inflammatory processes in the organ; it is based on the protein-polysaccharide-phospholipid complex which has three ultrastructural varieties. The pathogenesis of alcohol hyaline is complex. In addition to the metabolic and toxic effect of ethanol, it includes the following stages: (1) inhibition of dissemination of intermediate filaments synthesized by rough reticulum; (2) accumulation of filaments in cisternae of the rough endoplasmic reticulum and formation of fibrillar hyaline; (3) transformation of the fibrillar hyaline into granular one; (4) hepatocyte necrosis. Alcoholic hyaline as an autoantigen induces antibody production followed by the involvement of the immunopathological mechanisms.


Myelin basic proteins in myelin subfractions from normal and quaking mice. The relative proportions of four myelin basic proteins (preL, L, preS,S) were determined in myelin subfractions prepared from the forebrains of quaking and littermate control mice. The distribution pattern of each protein was similar in both mutant and control fractions. The S component was the only basic protein present in low amounts in myelin from the mutant.


Partial purification of tumour-specific transplantation antigens from methylcholanthrene-induced murine sarcomas by immobilized lectins. Plasma membranes isolated from two immunogenic, non-cross-protecting, MC sarcomas were shown to retain the specific rejection antigens of whole cells as well as serologically detected H-2 antigens. Solubilization of the membranes with sodium deoxycholate gave quantitative release of H-2 and retained the rejection specificity of the tumour from which it was derived. Polyacrylamide-gel electrophoresis (PAGE) showed no extensive degradation of membrane components during solubilization. The solubilized TSTAs were further characterized and purified on columns of 4 different lectins immobilized on sepharose beads. TSTA from both tumours bound to WGA but not to Con A, LCH or RCA columns. Specific activity was retained after elution from the WGA column. Serologically detectable H-2 bound to the Con A and LCH columns only. Clear separation of H-2 from TSTA activity was thus obtained. Furthermore the WGA-binding material represents a source for further purification of TSTA molecules in order to explore the basis for their diversity.


Occurrence of G gamma Hb F in Greek HPFH: analysis of heterozygotes and compound heterozygotes with beta thalassaemia. Haemoglobin F has been isolated from the red cells of individuals with the Greek form of hereditary persistence of fetal haemoglobin (HPFH), and the glycine/alanine composition of the gamma CB3 peptides determined. In contrast to previous reports we have shown that the Hb F of the Greek HPFH heterozygotes contains significant amounts of G gamma chains and circumstantial evidence indicates that these are the products of the same chromosome that carries the Greek HPFH determinant. Hence this chromosome must be directing the synthesis of G gamma, A gamma and (probably) beta and delta chains, thus implying that the Greek form of HPFH does not result from a deletion involving the globin chain structural genes. Analysis of the levels and structure of Hb F from the Greek HPFH heterozygotes and from separated cell populations from the Greek HPFH/beta thalassaemia compound heterozygotes indicate that the Greek HPFH determinant, while allowing an overall increase in gamma chain synthesis, is not the sole factor determining the absolute amount of Hb F production on a cellular basis.


A comparison of the homozygous states for G gamma and G gamma A gamma delta beta thalassaemia. One Arabic and two Indian patients with thalassaemia intermedia produce only Hb F for the G gamma type. Haemoglobin synthesis studies and genetic analysis indicate that they are homozygous for G gamma delta beta thalassaemia. The findings in these patients and their heterozygous relatives are compared with those in an individual homozygous for G gamma A gamma delta beta thalassaemia. From this analysis, and from previously reported data on G gamma A gamma delta beta thalassaemia, the phenotypic expression of the two varieties of delta beta thalassaemia is defined. The relationship between the clinical expression and molecular pathology of these forms of delta beta thalassaemia is discussed.


Granulocyte-specific alloantigen loss in chronic granulocytic leukaemia. The granulocytes of 23 patients with chronic granulocytic leukaemia were examined in the indirect immunofluorescence test and some also in the microleucoagglutination test, with specific alloantisera against the NA1, NA2, NB1 and ND1 antigens and a specific granulocyte xenoantiserum. In 10 cases a complete loss of alloantigens was detected. In one patient a partial loss was found. A significant correlation was established between this loss and an accelerated activity (impending blast crisis) of the disease.


Sickle cell trait and diabetic retinopathy. The presence of sickle cell trait and the prevalence and severity of retinopathy were assessed in 124 Negro diabetics. Sickle cell trait had no adverse effect on diabetic retinopathy.


Function of individual E. coli 30 S ribosomal proteins as determined by in situ immunospecific neutralization: a tentative classification. The accessibility of each 30S subunit protein to their cognate antibodies (IgG or Fabs) having been previously well established, the effect of their in situ specific neutralization by monovalent IgG fragments (FabI) are reported for five reactions: 1) T4 and R17 RNA directed protein synthesis: 2) polyphenylalanine synthesis: 3) enzymatic Phe-tRNA binding in the presence of 30S + 50W subunits: 4) fMet-tRNAf binding to the 30S subunit in the presence of initiation factors IF1, IF2, IF3; 5) coupling with lambda plac DNA transcription of the initial translation step (i.e., interaction of IF3 activated 30S subunits with nascent mRNA, in the absence of tRNA). According to evident similarities in their inhibition pattern concerning the five reactions tested, 30S subunit proteins can be classified in five categories which are discussed in terms of functional topography.


Localization of a gene: the nucleolar organizer. Nucleolus differentiates around the nucleolus organizer regions of the chromosomes or NORs. In the interphasic nucleoli the fibrillar centers are now considered as the NORs. The purpose of this editorial is to review the experimental data which allowed such identification. Our current concepts regarding this point result from three lines of evidence: 1) specific localization during nucleologenesis, 2) in situ hybridization with labeled ribosomal RNA or DNA, and 3) specific staining with silver.


Antigenic similarities between human plasma inhibitor of thrombin (At-III) and its analogues from other mammals. Cross reactions investigated by double immunodiffusion and by immunoelectrophoresis between human plasma and plasma of 5 animal species using a specific rabbit antiserum against human At-III revealed antigenic relationships between the antithrombins of these species. But the quantitative measurements of At-III by immunologic methods (electro-immunodiffusion and radial immunodiffusion), using the rabbit antiserum, were not possible in common laboratory animals, except in baboons.


Elevated serum beta 2-microglobulin levels and C1q-binding immune complexes in sarcoidosis. Serum beta 2 microglobulin levels were found significantly higher (3.05 +/- 0.98 mg/l) in 32 sarcoidosis patients without renal dysfunction than in normal controls (1.54 +/- 0.22 mg/l). Low levels of C1q-binding immune complexes were detected in 70% of patient's sera, despite the absence of extra-thoracic manifestations. C-reactive protein was detected in 55% of sarcoidosis sera. Neither C1q-binding immune complexes nor C-reactive protein were correlated with beta 2 microglobulin levels. Beta 2 microglobulin raised during relapses and fell under efficient corticosteroid treatment. Beta 2 microglobulin would represent a possible biological marker of disease activity.


5-Hydroxytryptamine and myoclonus induced by 1,2-di-hydroxybenzene (catechol) in the guinea-pig. Myoclonus induced by catechol in the guinea-pig is not altered by manipulation of cerebral 5-hydroxytryptamine (5-HT). The administration of catechol does not alter brain levels of 5-HT or its metabolite 5-hydroxyindole acetic acid. This form of myoclonus therefore is not of relevance to the 5-HT-sensitive post-anoxic action myoclonus occurring in man.


An analysis of xanthine dehydrogenase negative mutants of the rosy locus in Drosophila melanogaster. Eighteen alleles of the rosy locus in Drosophila melanogaster were characterized to identify putative nonsense mutants. Seven alleles exhibited no evidence of intragenic complementation, no evidence of immunological complementation, no evidence of immunological cross-reactivity to antibodies elicited by wild type xanthine dehydrogenase (XDH), and of course were completely deficient in measurable XDH activity. It is possible that one or more of these highly negative ry alleles are nonsense mutants. The remaining eleven ry alleles code for XDH molecules that retain some antigenic similarities to the wild type enzyme as assessed by immunoelectrophoresis and six of these eleven were capable of intragenic complementation.


Spiroplasmas: serological grouping of strains associated with plants and insects. Spiroplasma strains from plant and arthropod hosts, and from surfaces of flowers, were classified into three serological groups (designated I, II, and III) based on results from growth-inhibition tests. No significant cross reactions were observed among groups. The groupings were confirmed by ring-interface precipitin and microprecipitin tests, using membrane preparations as test antigens, and by organism-deformation tests. Serogroup I contained three subgroups: subgroup A (Spiroplasma citri strains Maroc R8A2 and C189), subgroup B (strain AS 576 and closely related strains from honeybee or flowers), and subgroup C (corn stunt spiroplasma strains). Serogroup II contained strains 23-6 and 27-31 isolated from flowers of the tulip tree (Liriodendron tulipifera L.) growing in Maryland. Serogroup III contained strains SR 3 and SR 9 isolated from flowers of the tulip growing in Connecticut. The subgroups of serogroup I were based on organism deformation, microprecipitin, and ring-interface precipitin tests. The data are consistent with the hypothesis that the three serogroups represent no less than three distinct spiroplasma species.


Regulation of internal solute concentrations of marine Vibrio alginolyticus in response to external NaCl concentration. Slightly halophilic marine Vibrio alginolyticus grown in the range of NaCl from 0.2 to 1.5 M maintained the total internal solute concentration always higher than the external medium by about 0.25 osM. The concentrations of macromolecules such as DNA, RNA, and protein were little affected by the increase in medium NaCl. The internal K+ concentration was kept to about 400 mM in the range of medium NaCl from 0.4 to 0.8 M; it rose to 510 mM when the bacterium was grown in 1.5 M NaCl, indicating that K+ increased only slightly in response to the large increase in medium NaCl. Thus, in contrast to the case of nonhalophilic and extremely halophilic bacteria, K+ was unlikely to act as a major component to regulate the internal solute concentration of marine V. alginolyticus. The internal Na+ and Cl- concentrations were maintained always lower than those in the growth medium, but they increased in response to the increase in medium NaCl. The concentration of internal Na+ was close to that of K+ at the concentration of medium NaCl that supports the optimal growth of this organism. The total amino acid content of V. alginolyticus increased from 76 to 413 mM by the increase in medium NaCl from 0.2 to 1.5 M. The concentrations of glutamic acid and prolined were 254 and 72 mM, respectively, when grown in 1.5 M NaCl. These results indicated that Na+, Cl- and amino acids, especially glutamic acid and proline, contributed to the regulation of internal solute concentration of V. alginolyticus in response to the increased external NaCl.


Pharmacokinetics of tallysomycin and bleomycin in the beagle dog. The pharmacokinetics of tallysomycin, a third-generation bleomycin analog, and bleomycin have been determined and compared in the beagle dog. Both compounds exhibited biphasic plasma elimination characteristics and were extensively absorbed after in injection. The elimination half-lives of tallysomycin after iv and im administration were 1.51 +/- 0.41 hours and 2.40 +/- 0.667 hours respectively. These values were longer than the comparable iv (1.01 +/- 0.19 hours) and im (1.12 +/- 0.39 hours) elimination half-lives for bleomycin. The volume of distribution in the central compartment after iv administration was 0.111 +/- 0.039 liter/kg for tallysomycin and 0.125 +/- 0.0723 liter/kg for bleomycin. The total apparent volumes of distribution were 0.706 +/- 0.255 liter/kg and 0.388 +/- 0.245 liter/kg for tallysomycin and bleomycin respectively after iv injection. These values were significantly different (P less than 0.05). Total urinary recovery in 24 hours for tallysomycin was significantly (P less than 0.05) less than that for bleomycin after both iv and im injections. These observed differences in pharmacokinetic behavior may, in part, account for differences in in vivo antitumor activities and toxic effects which have been reported for these drugs.


Cis-dichlorodiammineplatinum(II), methotrexate, bleomycin, and vincristine in head and neck cancer: a pilot study. Thirty-nine patients with advanced epidermoid carcinoma of the head and neck were treated with a combination of cis-dichlorodiammineplatinum(II), methotrexate, bleomycin, and vincristine. Twenty-nine patients were evaluable for response and 39 were evaluable for toxicity. With this regimen toxicity was acceptable and the following rates were observed in a total of 139 treatment courses: 100% (nausea and vomiting), 3% (decreased creatinine clearance), 4% (thrombocytopenia), 5% (leukopenia), and 2% (pulmonary fibrosis). There was one death due to sepsis during a period of chemotherapy-induced leukopenia. Although the patients treated with this regimen had advanced disease and had been treated aggressively previously, an overall response rate of 24% was observed, with three patients (10%) having a complete response. Median duration of response was 7 + months. These results indicate that this intensive combination chemotherapy has a sufficiently favorable risk/benefit ratio to allow its evaluation in randomized clinical trials in patients with head and neck cancer.


A radioimmunoassay for tallysomycin.

A radioimmunoassay for tallysomycin. Antibodies were raised against a new antineoplastic agent, tallysomycin, for use in a radioimmunoassay. The assay was sensitive to 2.5 ng of tallysomycin, had a coefficient of variation of 10.5% at 50 ng/ml, and was highly specific for tallysomycin A. The antibody exhibited reduced cross-reactivity with closely related tallysomycin analogs and little or no immunoreactivity with other antitumor antibiotics including bleomycin and phleomycin. Increased immunoreactivity occurred following copper chelation of tallysomycin B as compared with the non-chelated forms, thus indicating possible conformational alterations upon metal binding.


Role of the pituitary gland in experimental hormonal induction and prevention of benign prostatic hyperplasia in the dog. The antiandrogen, cyproterone acetate (CPA), prevents development of prostatic hyperplasia, induced in castrated dogs by a 6 month-treatment with 5 alpha-androstane-3 alpha, 17 beta-diol (A)alone or in combination with 17 beta-oestradiol (E2). The immunoperoxidase technique was used to study functional cell types in the pars distalis of the pituitary gland and to detect growth hormone (GH) and prolactin (PRL) target sites in the prostate gland. Homologous radioimmunoassays for estimation of serum canine GH and PRL concentrations were also performed. Treatment with the combinations A + E2 and A + E2 + CPA resulted in morphological indications of stimulated GH and PRL cells and depressed gonadotrophs. This correlates well with an increase in PRL-dependent staining in glandular epithelium and fibromuscular tissue of the prostate gland. However, basal serum PRL and GH levels were not significantly affected. Treatment with A and A + E2 stimulated, while additional treatment with CPA clearly suppressed adrenocorticotrophin/melanotrophin (ACTH/MSH) cells. These findings indicate that an endocrine imbalance in hypothalamic-pituitary-adrenal function may be involved in induction and prevention of prostatic hyperplasia in the dog.


Relationship between photoreceptor terminations and centrifugal neurons in the optic lobe of octopus. Retinal bundles, connecting the retina of the octopus to the ipsilateral optic lobe, contain both retinal photoreceptor axons that terminate in the optic lobe and centrifugal axons whose cell bodies lie within the lobe. Staining axonal elements in proximal stubs of individual retinal bundles by cobalt diffusion and subsequent sulphide treatment reveals the topographic relationship between afferent terminals and centrifugal cell bodies. At the outer border of the plexiform layer, stained terminal bags (photoreceptor axon enlargements), an indicator of photoreceptor terminal spread within this layer, overlap stained centrifugal cell bodies located within the inner granule layer. The details of this overlap indicate a dorsoventral representation of each retinal bundle within the optic lobe cortex.


Effect of mithramycin on widespread painful bone metastases in cancer of the breast. Fifteen patients with widespread painful osseous metastases from breast cancer unresponsive to other systemic therapy were treated with mithramycin at dose levels usually used for treating Paget's disease. Ten patients had relief of pain, which was marked and rapid in onset in seven. Mobility was greatly improved in four patients. Healing of bone lesions did not occur and new lesions developed while treatment was being given. Clinical response was associated with a decrease in plasma alkaline phosphatase. Toxicity was mild and consisted of nausea in most patients and a slight decrease in platelet count in one patient. Mithramycin is a useful agent for palliation of painful bone metastases and should be considered for further trials of combination chemotherapy for advanced breast cancer with bone metastases.


Cyclocytidine in the treatment of refractory acute childhood leukemia: a Southwest Oncology Group Phase I-II study. Thirty-seven children and adolescents with acute leukemia in relapse were treated with cyclocytidine in a cooperative group setting. Only one of the 27 evaluable patients achieved complete remission. A significant decrease (greater than or equal to 20%) in circulating and/or bone marrow leukemia cells occurred in an additional five patients. Drug toxicity was evaluated in 35 patients and included ten cases of jaw pain, two cases of hypotension, one case of fever, and one case of severe vomiting.


Arthropod-borne encephalitides in the Americas. The arthropod-borne encephalitides are an important cause of equine and human morbidity in the Americas. Between 1975 and 1978, 6970 human cases of arboviral encephalitis were reported in the United States of America; however, this represents only a fraction of the true incidence. St Louis encephalitis (4824 cases), California encephalitis (1035 cases), and western equine encephalitis (WEE, 947 cases) accounted for 98.5% of all reported infections. Approximately 1000-4000 cases of equine encephalitis occur annually in the United States, the majority due to WEE. In tropical America, important outbreaks of Venezuelan, eastern, and western equine encephalitis, and of Rocio encephalitis have occurred.In this article, epidemiological aspects of arboviral encephalitis outbreaks occurring within the past 5 years are reviewed. In addition, summaries of current research activities on the ecology and epidemiology of St Louis, western equine, Venezuelan equine, Rocio, and California encephalitis viruses are presented, and the problem of control of these infections is discussed.


Combination chemotherapy with vincristine, bleomycin, and methotrexate for advanced head and neck cancers. Thirty-three patients with a histologically confirmed diagnosis of advanced squamous cell carcinoma of the head and neck were treated with a combination of vincristine, methotrexate, and bleomycin. The regimen was as follows: Day 1, vincristine (2 mg iv) and methotrexate (200 mg/m2 iv over 24 hours); Day 2, bleomycin (15 mg/day by iv infusion for 48 hours). Folinic acid rescue began 36 hours after the start of methotrexate. The regimen was repeated at intervals of 3 weeks. Toxicity was minimal but the overall response rate was only 24% (three complete responses and five partial responses) and the median duration of remission was only 16 weeks overall. The combination of vincristine, methotrexate, and bleomycin in this dosage schedule has a response rate lower than that reported with single-agent treatment of advanced head and neck cancers.


[Mannosylation of lipid and protein acceptors in sheep lung microsomes]. In Sheep lungs, we have shown that a mannosyl-transferase activity is involved at microsomal level. This enzymatic system is able to catalyze the incorporation of mannose from GDP-mannose into two different endogenous acceptors: lipids and proteins. The mannolipid has the properties of a mannosyl-phosphoryl-polyprenol. The kinetic studies of product biosynthesis demonstrate that no precursor-product relationship exists in this system; this is an original behaviour of the lung in glycosylation phenomenon.


[Genetic analysis of interspecific crosses Mus musculus L. x Mus spretus Lataste: linkage of Adh-1 with Amy-1 on chromosome 3 and Es-14 with Mod-1 on chromosome 9]. 192 offsprings from interspecific back-crosses (male M. spretus x female BALB/c) F1 x male BALB/c or (male M. spretus x female C57BL6) F1 x male C57BL6 were analysed at thirteen structural loci. Linkage of ES-14 with Mod-1 on chromosome 9 and that of Adh-1 with Amy-1 on chromosome 3 are shown. The following order centromere/Car-2/Amy-1 is tentatively proposed for these loci on chromosome 3.


[Monolayer culture of adult mouse hepatic cells secreting albumin and alpha fetoprotein]. Adult mouse liver cells obtained by enzymatic dispersion were maintained in primary cultures for up to 4 weeks. They retained some of the typical morphological and ultrastructural characteristics of hepatocytes. After 2 days of culture, structures similar to bile canaliculi were found and after 6 days clusters of small proliferating cells were noticed in the gaps of the monolayer formed by large well-spread hepatocytes. Almost all 3-day cultures began to secrete alphafetoprotein for about 2 weeks, whereas albumin was secreted throughout the period of culture.


Measurement of pregnancy associated plasma protein A (PAPP-A). A method is described for measuring pregnancy associated plasma protein A (PAPP-A) in the maternal circulation during the 3rd trimester of pregnancy. The method used is a modification of Laurell's electroimmunodiffusion technique.


[Smoking and serum alpha 1-antitrypsin in 1296 healthy men (author's transl)]. Serum alpha 1-antitrypsin (alpha 1AT) was measured by radial immunodiffusion in 1296 healthy men aged 18--50 years. Other biological criteria, including leukocyte count and alpha 2-globulins were measured and the subjects were given a detailed questionnaire on their smoking habits. Results showed a very strong positive relationship between smoking and serum alpha 1AT: the heavy smokers had a serum alpha 1AT 20% higher than the non-smokers, and among subjects who stopped smoking, the level returned rapidly to normal. There were also close interrelationships between serum alpha 1AT, smoking, leukocyte count and a alpha 2-globulins. A discussion of these results is presented.


Alteration in the immunochemical dominance of determinants following the chemical modification of ox insulins: implications for the structure of the ox insulin monomer in solution. Insulins of differing species, together with chemically modified insulins, were used in cross-reactivity experiments employing selected antisera raised to ox insulin in the Harley guinea-pig. The immunogen had been administered as a water-in-oil emulsion, using H. pertussis vaccine as adjuvant. Antibody was generated by determinants in the C-terminus of the B chain plus the adjacent N-terminus of the A chain, in the central core of the A chain (A8-A14 region) and in its anti-parallel N-terminus of the B chain. From this antibody pool chemically modified ox insulin selected antibody to unaltered determinants. The immunochemical data were compatible with monomeric ox insulin being immunogenic, the immunogen perhaps being recognized by the immune system in the form of the Molecule-II rather than the Molecule-I of the dimer pair (as originally suggested by X-ray crystallographic data).


Cross-reactions between serum proteins and water soluble liver tissue antigens of the nine-banded armadillo (Dasypus novemcinctus Linn.) and man. Cross-reactions between serum proteins and water soluble liver antigens of the nine-banded armadillo (Dasypus novemcinctus Linn.) and man were studied by crossed immunoelectrophoresis (CIE). Armadillo serum tested with rabbit antiserum against human serum proteins gave twelve components in CIE. Nine of these cross-reacting proteins were identified and showed partial identity with the corresponding human proteins. The electrophoretic mobility of alpha 2-macroglobulin and Gc-globulin differed in the two species. An ultrasonicate of normal armadillo liver gave twenty-eight anodic and eight cathodic components in CIE. By absorption experiments with armadillo serum, twenty of the former and seven of the latter were shown to be liver tissue components. A combination of CIE and crossed-line immunoelectrophoresis (CLIE) revealed the presence of twelve anodic and six cathodic liver tissue components cross-reacting with man. A cathodic armadillo liver antigen called (CALA-17) showed partial identity with that of man both in tandem and fused rocket immunoelectrophoresis. The implications of the findings are discussed in relation to the use of armadillo-grown M. leprae for skin testing and other purposes in man.


Modulatory effects of oestrogen on immunological responsiveness. II. Suppression of tumour-associated immunity in patients with prostatic cancer. The effect of oestrogen (diethylstilboesterol diphosphate, DES-P) on immunity to tumour-associated antigens in patients with prostatic cancer was evaluated by leucocyte adherence inhibition, a suggested in vitro correlate of cellular immunity. Significant (P smaller than 0.05) suppression of immunity to malignant prostate was observed in thirty out of thirty-one patients following pre-incubation of their leucocytes with therapeutically significant levels of DES-P. Suppression of tumour-associated immunity by exogenous oestrogen provides further evidence to earlier studies demonstrating oestrogenic suppression of non-specific cellular responsiveness evaluated by mitogen-induced lymphocytic blastogenesis, and for concern over the efficacy of oestrogenic therapy and its adverse effect in the treatment of patients with hormone-dependent tumours and responsive diseases. The reduced efficiency of immunosurveillance of tumours and underlying infectious agents may contribute to the exacerbation of disease. While speculative, these observations may also be relevant to the possible assocition between uterine cancer and prolonged administration of DES and the development of vaginal tumours in offspring found in association with maternal ingestion during pregnancy.


Clinical significance of immunopathological findings in patients with post-pericardiotomy syndrome. II. The significance of serum inhibition and rosette inhibitory factors. Serum inhibition factors (SIF) that suppress phytohaemagglutinin-induced blast transformation of normal lymphocytes, and lymphocyte E-rosette inhibitory factors (RIF) that inhibit the T cell-specific property of E-rosette formation were determined in sixty-five patients before and after cardiac surgery. SIF was found in the first post-operative week in almost all patients; patients with complete post-pericardiotomy syndrome (PPS) still had these factors in the fourth postoperative week. The appearance of SIF correlated well with the intensity of the PPS. Persistence of SIF in eleven out of eighteen patients with clinically incomplete PPS reaffirms the probability that they had an 'immunologically' positive PPS. RIF was to be found in one third of the patients with complete or incomplete PPS and may be of prognostic value. The two factors were not identical.


DIODA: delineation and feature extraction of microscopical objects. A computer program is described for delineation and measurement of microscopical objects, such as cells and chromosomes, which may have been scanned using absorbance, fluorescence or reflectance microscopy. The quality of the object delineation is optimized through the controur ratio, which is simply computed from the object contour. Geometrical features, like the perimeter and area are computed. A new definition is introduced for the background region, especially suited for the analysis of closely packed objects. This definition is based upon a comparison between total staining material content values resulting from a variety of methods and circumstances. The program is principally intended for use in the on-line real-time environment of a small laboratory computer, but may be used off-line as well. It has facilities for displaying the results and the process by which they are produced. A program module is described for displaying scan data on a bilevel display using an adaptation of the sigma-delta method.


Effects of gibberellic acid and of tunicamycin on glycosyl-transferase activities and on alpha-amylase secretion in barley. A crude membrane fraction was prepared from isolated aleurone layers, the secretory tissue of barley grains. The layers were pre-incubated in the presence or absence of the phytohormone gibberellic acid. The membranes catalyzed the transfer of [14C]mannose from GDP-[14C]mannose and of N-[14C]acetylglucosamine from UDP-N-[14C]acetylglucosamine to endogenous and exogenous dolichyl monophosphate. When gibberellic acid was present during the pretreatment the activity of the transferases was increased by a factor of two to three. A significantly increased activity was observable within four hours after the addition of gibberellic acid, whereas the gibberellic-acid-induced secretion of the glycoprotein alpha-amylase started only after 12 h. Tunicamycin inhibited the secretion of alpha-amylase by 60 to 80%. Intracellularly, however, no alpha-amylase was found to accumulate. On the other hand, tunicamycin did not inhibit the rate of total protein synthesis by more than 10%. The possibility is discussed that the synthesis of the protein portion of glycoproteins is specifically inhibited, when glycosylation is prevented.


Regulation of Ca2+ efflux from kidney and liver mitochondria by unsaturated fatty acids and Na+ ions. The effects of fatty acids and monovalent cations on the Ca2+ efflux from isolated liver and kidney mitochondria were investigated by means of electrode techniques. It was shown that unsaturated fatty acids and saturated fatty acids of medium chain length (C12 and C14) induced a Ca2+ efflux from mitochondria which was not inhibited by ruthenium red, but was specifically inhibited by Na+ and Li+. The Ca2+-releasing activity of unsaturated fatty acids did not correlate with their uncoupling activity. In kidney mitochondria a spontaneous, temperature-dependent Ca2+ efflux was observed which was inhibited either by albumin or by Na+. It is suggested that the net Ca2+ accumulation by mitochondria depends on the operation of independent pump and leak pathways. The pump is driven by the membrane potential and can be inhibited by ruthenium red, the leak depends on the presence of unsaturated fatty acids and is inhibited by Na+ and Li+. It is suggested that the unsaturated fatty acids produced by mitochondrial phospholipase A2 can be essential in the regulation of the Ca2+ retention in and the Ca2+ release from the mitochondria.


Macroamylasaemia following the infusion of low molecular weight-hydroxyethyl starch in man. In fasted normovolaemic subjects dosed with 400 ml of 14% low molecular weight-hydroxyethyl starch (LMW-HES, Mw 264,000 daltons, Mn 63,000 daltons, Mw/Mn = 4.2, MS = 0.43), an increase in the concentration of alpha-amylase was observed in blood which exceeded the upper limit of normal (190 U-1(-1), and in all cases reached twice the basal value. Concomitant with this elevated activity in the blood, the urinary excretion of this enzyme was significantly reduced. Gel filtration of serum recovered from 1 subject on a column of Sephadex G-100 revealed the presence of an LMW-HES-induced macroamylase, detectable for up to 6 h post-injection. This induced alpha-amylase-LMW-HES complex is apparently of a molecular weight that is not easily filtered at the renal glomerulus, thus accounting for the observed hyperamylasaemia concomitant with the decrease in renal excretion. By 12 h post-injection however, the high activity of alpha-amylase in the blood was returning to normal levels and this was observed to parallel the reduction in the formation of macroamylase complexes in serum.


Vasoconstrictor effect of midodrine, ST 1059, noradrenaline, etilefrine and dihydroergotamine on isolated human veins. ST 1059, the pharmacologically active metabolite of midodrine, is a powerful vasoconstrictor compound, acting by stimulation of alpha-receptors. It elicited 80% of noradrenaline-induced contraction of human veins.


Ontogeny of immunity in amphibians: changes in antibody repertoires and appearance of adult major histocompatibility antigens in Xenopus. Larval Xenopus anti-2,4-dinitrophenyl antibodies of the low-molecular weight type can be analyzed by isoelectric focusing (IEF). Within a clone of genetically identical animals, tadpoles make antibodies whose IEF spectrotypes are shared by most of the individuals. Adults of the same clone also make antibodies of identical spectrotype, but the adult pattern can be very different from the larval one, although both responses are heterogeneous. The larval spectrotypes that one cannot see in a primary adult response can be found if the adult has been primed during larval life and boosted after metamorphosis. The heterogeneity of the response is somewhat lower in tadpoles (up to 12 antibody IEF bands) than in adults (up to 20 antibody IEF bands). The change in the repertoire occurs during metamorphosis at the time of the appearance of two major histocompatibility complex antigens. One, a lymphocyte antigen, appears 10-15 days before the end of metamorphosis, the other, present on red cells (and presumably also on lymphocytes), appears 1.5 month after the end of metamorphosis, as determined by immunofluorescence analysis. During the same period, the syngeneic mixed leukocyte reaction switches from a larval anti-adult to an adult anti-larval reaction.


The fine specificity of regulatory T cells. IV. Idiotypic complementarity and antigen-bridging interactions in the anti-lysozyme response. The hen egg-white lysozyme (HEL)-specific B cells which are activated in response to HEL share a cross-reactive idiotype as well as submolecular specificity. Helper T cells of two different specificities are implicated in their optimal activation, one recognizing the idiotype and the other, an epitope on the HEL molecule opposite to the one recognized by B cells. Thus, efficient T-B collaboration involves both idiotypic complementary and antigen bridging.