Differential diagnosis of typical and atypical congenital achromatopsia. Analysis of a progressive foveal dystrophy and a nonprogressive oligo-cone trichromasy (general cone dysfunction without achromatopsia), both of which at first had been diagnosed as achromatopsia. Report on two patients whose symptoms suggested the presence of congenital achromatopsia. In one case there was indeed total colour blindness, but a normal photopic ERG. Here, achromatopsia is the present stage in a process of slow functional decay of the central retina. Most probably the underlying disorder is progressive foveal dystrophy, a central form of cone dystrophy. In the other case there was a nonrecordable photopic ERG, but trichromatic colour vision. This appears to be another patient with oligo-cone trichromasy (general cone dysfunction without achromatopsia), as described by Van Lith.


Electron microscopy of the early embryonic development of the human corneal epithelium. The eyes of a human embryo in the 6th week, 11 mm crown-rump (C.R.) length, and of a human embryo in the 7th week, 19 mm C.R. length, were examined. In the embryo of 11 mm C.R. length, the lens vesicle had just detached from the surface ectoderm, the presumptive corneal epithelium. The acellular primary corneal stroma appeared between the lens vesicle and the overlying ectoderm. The fine structure of the ectodermal cells, of their basal lamina, and of the primary stroma is described. In the embryo of 19 mm C.R. length, mesenchymal cells had moved from the periphery into the space between the ectoderm and the lens. There were remarkable changes in the structure of the corneal epithelial cells, in their basal lamina, and in the underlying substances of the primary stroma.


[The influence of cryoprotective solutions on the ultrastructure of rabbit corneal endothelium (author's transl)]. A series of rabbit corneae was preserved at -196 degrees C in liquid nitrogen using five different cryoprotective solutions: (1) 5% dextran T 40, (2) 10% polyvinylpyrrolidone, (3) 5% dextran T 40 + 10% polyvinylpyrrolidone + dimethyl sulfoxide, (4) 25% rabbit albumin + 10% polyvinylpyrrolidone, (5) 25% rabbit albumin + dimethyl sulfoxide. After thawing the corneae, the influence of the different cryoprotective solutions on the ultrastructure of corneal endothelium was evaluated and compared with fresh corneae. The results were as follows: (1) Using 5% dextran T 40 or 10% polyvinylpyrrolidone or 25% rabbit albumin as cryoprotective solutions marked intracellular damage. (2) Adding dimethyl sulfoxide to the solutions cryopreservation appeared to be more successful at the cellular basis, despite the freezing and thawing procedure mediated moderate intracellular changes. Cryopreservation including dimethyl sulfoxide renders better conditions for successful corneal grafting in the light of ultrastructural aspects.


beta-Ray treatment of malignant epibulbar melanoma. Sixty-eight patients suffering from conjunctival melanoma were treated by beta-irradiation. The dose given ranged between 15,000 and 20,000 rd at the tumor surface. In 75% the therapy was successful. In 67,4% the melanoma could be cured by beta-irradiation alone with a follow-up period between three and ten years. The lethality rate from proven metastases was only 6.2%. The regression time after beta-therapy, as a rule, exceeded several months. Beta-rays can be used either primarily or after tumor excision. Care should be taken that the applicator covers all the tissue containing tumor cells.


Anterior segment reactions after experimental trauma to rabbit eyes. The effect of experimentally induced uniocular trauma was investigated in the adult albino rabbit by means of iris fluorescein angiography. Paracentesis, blunt trauma, occlusion of all four vortex veins or of the two long posterior ciliary arteries, or local instillation of nitrogen mustard, were performed in a number of animals, some of which received systemic aspirin preoperatively. Iris angiograms of the injured and the contralateral eye were performed immediately after the traumatic insult. The injured eye always showed an increased permeability to fluorescein. Except for paracentesis, the ipsilateral response often included ischemia of the iris. The contralateral eye always showed an increase in fluorescein permeability into the aqueous. In some cases, sector ischemia of the contralateral iris was seen. Aspirin inhibited some ipsilateral responses but had no effect on the consensual reactions. It is concluded that ipsilateral trauma almost invariably causes a contralateral reaction in the rabbit eye, which is more severe if the injury creates ischemia of the iris. Since these reactions are inefficiently blocked by aspirin, they are not prostaglandin-mediated. The interocular pathway involved may be neural or vascular in nature.


Biochemical and histochemical response to a complete epithelial denudation of the rabbit cornea. Alkaline and acid phosphatase. Activities of alkaline and acid phosphates were investigated in rabbit corneas after a complete epithelial denudation in vivo (limbus to limbus). Dynamics of enzymatic changes during corneal healing were followed quantitatively in homogenates of regenerated epithelium and stroma (denuded cornea) and in cryostate frozen sections on days 1, 4, 7, 14, and 28. Biochemical and histochemical findings at these times showed a different response in each enzyme. Acid phosphatase displayed a gradual increase of activity in epithelium as well as in stroma; on day 28 after injury its content was normal. In contrast, alkaline phosphatase showed delayed activity during the repair process, and even a month after de-epithelization was still subnormal, particularly in superficial layers of epithelium.


Experimental corticosteroid ocular hypertension in the rabbit. Weekly subconjunctival injections of 4mg repository betamethasone, repeated over three weeks, produced a sustained increase of intraocular pressure (IOP) in 96% of the treated rabbits. Treatment was generally well tolerated and important systemic toxic effects were present only in a few animals. The ocular hypertension so obtained was constant, well reproducible and sensitive to antiglaucoma drugs. The authors believe they have developed an animal model which is very suitable for testing the pressure-lowering effect of drugs and for other studies on ocular hypertension and glaucoma.


Prevention of cystoid macular edema after lens extraction by topical indomethacin (III) radioimmunoassay measurement of prostaglandins in the aqueous during and after lens extraction procedures. The amounts of Prostaglandin (PG) E and F2alpha in the aqueous humor were measured by radioimmunoassay techniques before and immediately after intracapsular and extracapsular cataract extractions. We found that: 1. The levels of PG E and PG F2alpha are elevated by cataract extraction. 2. The elevated levels of PGs can all be prevented by preoperative applications of topical indomethacin. 3. No differences in the amounts of PGs biosynthesized during intracapsular and extracapsular lens extraction were found. 4. In some cases, the levels of PG E were still elevated one week after surgery. These findings were used as the basis for our attempts to define the causes of cystoid macular edema (CME) following lens extractions.


Leiomyoma of the ciliary body.

Leiomyoma of the ciliary body. Clinical, histological, and electron-microscopic study of a leiomyoma of the ciliary body, which was removed by cyclectomy from the right eye of a 55-year-old female patient. This is the second case in the literature in which an excision has been performed and the diagnosis been confirmed by electron microscopy. The differential diagnosis between amelanotic malignant melanoma, schwannoma, and neurofibroma is discussed, and the electron-microscopic characteristics of a leiomyoma are demonstrated.


N-hexane maculopathy in industrial workers. A neuro-ophthalmologic examination, including fluorescein angiography and colour discrimination tests, was made of 15 workers (age range 30--65 years, mean 45.8 years) exposed to n-hexane (range of exposure 5--21 years) during vegetable oil extracting and adhesive bandage manufacturing. Visual acuity, visual fields, intraocular pressure, and biomicroscopical findings were normal. Ophthalmocopy revealed delicate macular changes in 11 or the 15 subjects. One subject had a history of central serous retinopathy in one eye. The macular changes consisted of an orange-like ophthalmoscopic appearance and a decreased macular lustre. Subtle defects of the pigment layer were present in the fluorescein angiography. Defective colour discrimination was found in 12 of the 15 subjects, one of whom had congenital deuteranopia. Colour defects were of the acquired type, mainly in the blue-yellow spectrum. Damage to the receptor lipids is suggested as the pathomechanism of the maculopathy found in this study.


The distribution in the eye and the effect on intraocular pressure of clonidine. The distribution of [14C]-clonidine in the eye after intravenous administration and injection into the external carotid arteries was studied in a comparative manner in anesthetized cats. The amount of clonidine accumulated in the eye after intraarterial administration by far exceeded that after intravenous application. In addition the pharmacological effects of clonidine obtained by these two routes of administration were investigated and analyzed. The decrease in intraocular pressure after intravenous administration appears to be much stronger than after intraarterial injection. Obviously, there exists no direct correlation between the clonidine concentration in the eye and the ocular hypotensive effect of this drug.


[Disturbances of the pupil reflex associated with lesions of the upper visual pathway (author's transl)]. In six patients with ischemic lesions of the visual pathways above the lateral geniculate body, the pupil light reflex was investigated under perimetric conditions. The size of the lesions--in four cases caused by lateralized cerebral infarction, in two cases by complicated migraine attacks--was certified by neurological examination and by angiography or computerized tomography respectively. The recordings were done with a portable pupillograph measuring the infrared light reflected from the iris. A Tübinger perimeter served as stimulator. All patients except one, whose visual fields recovered quickly and completely, showed parallel tracings concerning the sensory and the pupillographic profiles, in the older lesions as well as in the recent ones.


Primary position vertical nystagmus: 'directional preponderance' of the pusuit system? The essential disturbance in five patients with vertical nystagmus was an inability to generate smooth pursuit eye movements in the direction of the quick phase of their nystagmus. As the cause of this behavior, the authors suggest an asymmetric impairment of the visual input to the pursuit system. This defect causes a 'directional preponderance' of the pursuit system detectable as a continuous drift off target. The drift is interrupted by refoveating saccades, thus resulting in a vertical nystagmus.


The significance of the arginine and arginase of tears in experimentally-induced herpes simplex corneae. Experimental corneal herpes is always accompanied by the accumulation of arginine, the substrate of arginase, in tears, ensuring the multiplication of the herpes hominis virus. The main source of the large amount of arginine is the desquamating corneal epithelium, since after the epithelium of the cornea is abraded the arginine content of the tears again equals that of healthy tears. The low arginase content of rabbit tears can be supplemented by arginase applied as eyedrops, and this results in the cure of the herpetic process.


[Caustic burns of the oesophagus in the adult. Histopathological study of 12 cases (author's transl)]. A histopathological study of 12 cases of major caustic burns of the oesophagus serves as a basis for a description of the lesions and to demonstrate the inexorable progression to fibrosis. The lesions are most frequantly diffuse, regardless of the substance responsible. Four morphological stages may be distinguished, superimposed on the clinical picture.


Chloramphenicol and phenobarbitone--a drug interaction. Two infants with meningitis who were treated with phenobarbitone and high-dose chloramphenicol showed progressive falls in the peak blood levels of chloramphenicol. A standard chloramphenicol dose of 50 mg/kg daily would have produced subtherapeutic blood levels after only a few days. The importance of measuring serial blood chloramphenicol concentrations is stressed.


Effects of hypertonic perfusion on the ultrastructure of frog cardiac muscle. The ultrastructural changes induced by hypertonic perfusion were investigated using the ventricular muscle of the bullfrog. It was demonstrated that the fixative tonicity critically affects the ultrastructure. Effects of sucrose-, NaCl- and urea-hypertonicities were investigated and compared. In both sucrose- and NaCl-hypertonic media, although the cardiac muscle strongly shrank and the extracellular spaces markedly increased according to increasing tonicity the width of the intercalated disc cleft remained unchanged and the cleft was never separated even in 3 times hypertonicity. The sucrose-hypertonicity made the feature of the fine structure extremely obscure and the electron densities in both the Z-line and the intercalated disc region markedly decreased. When both the perfusate and fixative were made hypertonic by urea, which is known to easily penetrate the cell membrane, a shrinkage of the myocardial cells was observed but to a lesser extent as compared with sucrose or NaCl. The striation pattern was disordered in this condition though the intercalated discs were never affected.


Corynebacterium endophthalmitis. Laboratory studies and report of a case treated by vitrectomy. A Corynebacterium sp was isolated from the vitreous humor under aseptic conditions on two separate occasions from a patient with endophthalmitis resulting from a penetrating injury by a metallic foreign body. The metallic foreign body was removed during a pars plana lensectomy and anterior vitrectomy procedure; intravitreously injected methicillin sodium, gentamicin sulfate, and dexamethasone sodium phosphate gave a functional visual result. Intravitreous inoculation of rabbits with the Corynebacterium isolate produced an endophthalmitis similar to that produced in the patient, and subsequent cultures from the vitreous of the inoculated rabbits grew the same Corynebacterium sp. To our knowledge, this is the  first reported case of endophthalmitis in which a Corynebacterium sp was documented by intraocular culture.


Modification of constant optokinetic nystagmus by vestibular stimuation. Experiments were conducted to quantify the effect of a vestibular stimulation of known magnitude on a constant optokinetic nystagmus (OKN). Ten normal human subjects were tested with varying magnitudes of vestibular stimuli that were superimposed on a constant 30 degrees optokinetic stimulus. The gain of the vestibular system in the dark was 0.42 +/- 0.11, and the gain in the light during superimposition testing was 0.12 +/- 0.02. From these results, predictions were made that the degree of vestibular imbalance necessary to produce an asymmetric OKN would generate a spontaneous nystagmus in the dark, which would be equivalent to 20 to 30 degrees. Data from a large group of patients were used for corroboration of the results.


Isolation and partial characterization of the major sialoglycoprotein of human T-lymphoblastoid cells of a MOLT-4B cell line. A sialoglycoprotein with an approx. mol.wt. of 95000 was isolated from human lymphoblastoid cells of a MOLT-4B cell line, which was of human T-lymphocyte origin, by ion-exchange chromatography, affinity chromatography on a column of wheat-germ agglutinin-Sepharose and preparative slab-gel electrophoresis. The localization of this glycoprotein on the cell surface was indicated by surface labelling by the periodate/NaB3H4 and lactoperoxidase-catalysed iodination methods. Carbohydrate analyses of this glycoprotein revealed that its total carbohydrate content is 28% (w/w), and it contains fucose, galactose, mannose, N-acetylglucosamine, N-acetylgalactosamine and sialic acid in molar proportions 1.0:4.0:3.7:3.5:1.2:2.5, suggesting that it has two types of sugar chain, i.e. sugar chains like those of serum glycoproteins and sugar chains of the type found in mucins. Actually, alkaline borohydride treatment of this glycoprotein yielded tri- and tetra-saccharide, the latter containing 1 molecule of fucose in addition to each molecule of galactose, N-acetylgalactosamine and sialic acid. This glycoprotein bound to Ricinus communis agglutinin and concanavalin A as well as to wheat-germ agglutinin.


Proteinase-sensitive release of enzymes from pancreatic microsomal fraction. Suspensions of rat pancreatic microsomal fraction release alpha-amylase and ribonuclease on incubation at 37 degrees C, but not at 2 degrees C. The release is abolished by proteolytic enzymes. Ribonuclease associated with the microsomal fraction is protected from subtilisin BPN' attack, but is sensitive after release.


Alpha-1-antitrypsin phenotypes in rheumatoid arthritis and systemic lupus erythematosus. Alpha-1-antitrypsin phenotypes were determined in 37 patients with rheumatoid arthritis and 40 patients with systemic lupus erythematosus. No significant increase in non-MM phenotypes was found. It appears that alpha-1-antitrypsin phenotypes neither predispose to the development nor enhance the severity of the two rheumatic diseases.


Detection of low avidity anti-DNA antibodies in systemic lupus erythematosus. The binding of sonicated, radiolabeled DNA by systemic lupus erythematosus (SLE) sera was measured by a high sensitivity polyethylene glycol (PEG) precipitation assay. This method is considerably more sensitive than currently used techniques. The results suggest that a significant concentration of low avidity antibodies is present in SLE sera; however, these antibodies are not detected by conventional techniques.


Anti-dsDNA and complement profiles as prognostic guides in systemic lupus erythematosus. Antibodies to dsDNA, tested with circular DNA in the Farr assay, are specific for systemic lupus erythematosus. A longitudinal study showed a clear relation between the clinical state, the anti-dsDNA titer (expressed in units), and the C1q and C3 levels: when anti-dsDNA levels remained high, no exacerbations were observed. A sharp drop in anti-dsDNA, usually preceded by a rise, was related to a serious exacerbation. Only during the exacerbation when both C1q and C3 were very low was renal involvement seen.


Rheumatology. What should students know? The majority of patients with rheumatologic problems are seen and followed by nonrheumatologists. Of concern is the perception that a significant number of United States medical schools do not have adequate teaching programs in the rheumatic diseases. Two thousand two hundred and seventy practicing physicians, trainees, and medical students were surveyed in the Intermountain West to determine what they think undergraduate medical students should learn about rheumatology. Most respondents felt that common diseases and problems should be emphasized and that basic skills in history taking and physical examination are more important than disease related information.


[Behavior of the blood calcium in operations during extracorporeal circulation]. The Authors analyse the variation of the calcium plasmatic concentration during extra corporeal circulation (E.C.C.). The Authors remind the importance of the calcium plasmatic concentration preserving a good cardiac output. They say that amount of calcium given assures a good plasmatic concentration and aid the cardiac output after E.C.C. The possible hypercalcemia after A.C.D. blood transfusion doesn't compromit the cardiovascular function.


Preliminary studies on the uptake of labeled mammalian gonadotropins by ovary and oviduct of the green frog, Rana esculenta, in vivo. In hypophysectomized females, Rana esculenta, a significant uptake of labeled ovine FSH and LH was evident in both the ovary and oviduct. This binding was specific only for the ovary. Ovariectomy did not modify the affinity of the oviduct for these gonadotropins. The possibility of the presence of discrete receptor molecules for FSH and LH in the ovary of Rana esculenta is discussed.


Diamond-Blackfan syndrome: evidence for T-cell mediated suppression of erythroid development and a serum blocking factor associated with remission. Diamond-Blackfan syndrome may be a disorder of cellular immunity. Lymphocytes from some patients are capable of suppressing erythropoiesis in cultures of normal bone marrow. We studied two adults with this disorder, both in complete unmaintained remission, using a technique for cloning peripheral blood erythroid precursors (BFU-E) in culture. The BFU-E may be early, erythropoietin sensitive, erythroid committed stem cell. Under culture conditions, which employ fetal calf serum, neither patients cells formed normal numbers of erythroid colonies. Controls yielded 15.3 +/- 5.2 BFU-E/2.5 X 10(5) mononuclear cells. Culture of patients cells using autologous serum, promoted more normal growth of BFU-E (21.4 +/- 6.9 and 7.3 +/- 2.3 BFU-E/2.5 X 10(5) cells). Patient mononuclear cells, cocultured normal cells, generally suppressed BFU-E generation. Cocultures of normals were not inhibitory. Removal of T-lymphocytes from patient mononuclear cells permitted normal growth of BFU-E in coculture with controls. T-cells depleted Diamond-Blackfan mononuclear cells showed BFU-E formation in fetal calf and autologous serum. Diamond-Blackfan T-cells inhibited BFU-E formation by normal mononuclear cells. The cellular defect in Diamond-Blackfan syndrome persists during complete remission and may be mediated by lymphocytes. The development of a serum factor which blocks the suppressive effects on erythroid precursors of a subpopulation of autologous T-cells may be responsible for the development of remission in our patients.


Water movement across split frog skin.

Water movement across split frog skin. A net inward fluid reabsorption (salt-linked flow) has been observed in isolated skin epithelium (split skin) with the same magnitude as in whole skin when identical NaCl Ringer solutions were used to bathe both sides. Split skins also respond to a hyperosmotic sucrose solution bathing the outer (epithelial) surface by generating an outward osmotic flow. A non-linear relationship between osmotic flow and the osmotic gradient has been found in split skin similar to that found in whole skin.


[Increase in the activity of an epileptogenic focus in frog hippocampus as a result of kynurenines and its reduction by serotonin]. In frogs with epileptogenic focus induced by injection of penicillin (1000 U in 0.4 microliter) into the primordial hippocampus it was shown that pretreatment with two kynurenines (quinolinic acid -- 0.1 microgram, and d,l-kynurenine -- 1 microgram) into the focus region and their injection into the functioning epileptogenic focus led to a sharp increase of the interparoxysmal epileptiform discharges and electrographic correlates of the fit on the EEG. Anthranilic acid (5 microgram) did not influence the activity of epileptogenic foci, and serotonin (1 microgram) and 5-methoxytryptamine (1 microgram) decreased it significantly. It is suggested that the effect of kynurenines on neurones in the epileptogenic foci may play a certain role in the pathogenesis of epilepsy.


[Cross reactions in the H-2 system of cytotoxic T-lymphocytes concentrated by the adsorption-elution method on target cell monolayers]. Cytotoxic T-lymphocytes (CTL) obtained by in vivo immunization were enriched by the absorption-elution technique, using the relevant allogeneic target cell (TC) monolayers. After the separation of C57BL anti-A (anti-KkDd) lymphocytes into anti-Kk and anti-Dd subpopulations they displayed cross killing cytotoxic effect on H-2d and H-2kTC, respectively. B10D2 anti-B10 (anti-KbDd) lymphocytes cross reacted to H-2a and H-2q TC. The results are discussed in the light of heterogeneity of CTL clones or their receptors.


[Replacement of the helper function of T cells by an RNA-containing antigen-specific lysis factor]. The lymph node viable cells suspension of immunized mice was centrifugated. The supernatant was chromatographed in Sephadex G-200, and fractions were deproteinized. The deproteinized third fraction (Mol wt 30000) stimulated specifically the plaque-forming cells of intact mice immunized by SRBC. It restored the capacity to antibody production in the lethally irradiated intact mice protected by the syngeneic bone marrow. The activity of this fraction disappeared following treatment with RNA-ase, but not with DNA-ase or trypsin. The first and the second deproteinized fractions of the supernatant inhibited non-specifically the viable lymph node cells of the immunized animals in the intact mice immunized with SRBC.


[T- and B-lymphocytes of guinea pigs sensitized to ragweed pollen]. Functional activity of T and B lymphocytes in guinea pigs sensitized with common ragweed pollen was investigated. The content of T and B rosette-forming cells (T RFC and B RFC) was studied in guinea pigs following sensitization with common ragweed pollen. It was shown that the amount of B RFC in the regional lymph nodes at the early period of sensitization was over 4 times greater than that of the B RFC in normal animals. Functional capacity of T cells during the sensitization determined in the rosette-formation test altered less than the analogous capacity of B cells.


Experimental study of some features of the etiology and pathogenesis of motion sickness. A study was made of vestibular stability in man as affected by acceleration in various directions and of acceleration affecting receptors of the vestibular apparatus with varying frequency. It was established that tolerance for vestibular stimulation in certain individuals may be affected by direction of acceleration and frequency of the action. Individual susceptibility to motion sickness is widely expressed under conditions of specific vestibular stimulation. The results obtained indicate that development of motion sickness does not depend on the activity of the vestibular analyzer and motion sickness is not its specific vestibular reaction. Motion sickness is a reaction of the whole organism and its manifestation under long stimulation of receptors of the vestibular apparatus in individuals predisposed to motion sickness depends on specific features of the activity of the limbico-reticular complex.


[Pharmacokinetics of antineoplastic agents (author's transl)]. The general basis of pharmacokinetics are summarized with the clinical aims of a better utilisation of drugs by the application pharmacokinetic data. The subject is illustrated by some antineoplastic agents especially on high dose methotrexate regimens and clinical use of 5 FU. A pharmacokinetic model may be described with the first agent but for 5 FU no specific model has yet been demonstrated. Some examples of studies on adriamycin and cytosine arabinoside are then given.


Diet, sunlight, and 25-hydroxy vitamin D in healthy children and adults. In 110 white West Midlands children serum 25-hydroxy vitamin D (25-OHD) concentrations showed a pronounced seasonal variation, the values being highest in August and lowest in February. The concentrations correlated significantly both with recorded sunlight and with seasonal ultraviolet energy of the sunlight. Children who had had a seaside holiday the previous summer had a higher mean 25-OHD concentration than those who had not had a summer holiday away from home. Correlation between vitamin D intake and serum 25-OHD concentration was not significant.


Choline acetyltransferase and acetylcholinesterase containing projections from the basal forebrain to the amygdaloid complex of the rat. The origin of the cholinergic innervation to the amygdaloid complex was investigated with the use of acetylcholinesterase (AChE) histochemistry and choline acetyltransferase (ChAT) assay of microdissected nuclei. Visualization of AChE-positive neurones in the ventral forebrain was facilitated by pretreatment of rats with 1.5 mg/kg di-isopropyl phosphofluoridate (DFP). The AChE-positive neurones in the ventral forebrain are distributed in a continuous system from the septum through the lateral preoptic area to the entopeduncular nucleus caudally. Knife cuts or kainic acid injections (1.5 microgram/l microliter) placed in the lateral preoptic area resulted in substantial depletion of the AChE and ChAT content of the amygdala nuclei. Kainic acid injections (1.5 microgram/l microliter) in the diagonal band area or cuts through the stria terminalis dorsally did not significantly modify the AChE staining or ChAT content of the amygdala (although diagonal band injections partially depleted the hippocampus of ChAT). Knife cuts severing both the so-called ventral pathway and the stria terminalis did not produce significantly greater ChAT depletion in the amygdala than those produced by the knife cuts or kainic acid injections in the lateral preoptic area. Parasagittal knife cuts undercutting the lateral pyriform cortex also failed to modify the AChE or ChAT content of the amygdala, but they depleted the undercut cortex of both ChAT and AChE; AChE-positive material accumulated ventrally and medially to the knife cut. It is suggested that the major source of the cholinergic innervation of the amygdala is the magnocellular AChE-positive neurones in the lateral preoptic area and adjacent regions of the ventral forebrain.


Pseudophakic bullous keratopathy. A clinical-pathologic analysis. Of 226 patients who had an intraocular lens implanted over a three year period, 6.2% developed bullous keratopathy compared with 2.2% of 90 patients who had a standard cataract extraction performed by the same surgeon. An additional 4.0% of the lens implant patients developed peripheral or intermittent corneal edema. The factors related to the higher incidence of this complication in lens implant patients included corneal touch during implantation, prolonged postoperative iritis and, in cases of mild or peripheral corneal edema without bullous keratopathy, recurrent lens dislocation. The most consistent pathologic findings in 10 corneas that required keratoplasty were epithelial edema and loss of corneal endothelium. Means to prevent this complication are discussed.


A comparative study of b- and d-waves of the electroretinogram, in frogs (Rana catesbeiana). The aim of this study was to compare the b- and d-waves of the ERG, evoked respectively by ON and OFF  stimuli. The experiments were carried out on frogs. The d-wave is facilitated by light adaptation and relatively high stimulus intensity. The depth profiles of b- and d-waves are different. Aspartic acid abolished only the b-wave whereas nembutal affected the d-wave. These results suggested that b- and d-waves were produced by separate neuronal mechanisms, even though both appeared as positive deflection in the corneal ERG and were sensitive to K+ ion.


Granulocytosis and colony-stimulating activity (CSA) produced by a human squamous cell carcinoma. A patient with a squamous cell carcinoma accompanied by a marked granulocytosis (100,000/mm3) of unknown origin was examined for Colony-Stimulating Activity (CSA). The pleural fluid and the tumor extract revealed high CSA. The floating cells in the pleural fluid were successfully transplanted into nude mice as a localized tumor with cyst formation. The tumor invariably caused a marked granulocytosis (100,000--300,000/mm3) with induction of a conspicuous splenic granulopoiesis in the transplanted mice. High CSA were demonstrated in their cystic fluid as well. Media conditioned by the primary cultures of these tumor cells revealed the same CSA, demonstrating the direct production of CSA by the tumor itself. These results indicate the presence of human CSA producing tumor and that such a tumor may in part account for a marked granulocytosis of unknown origin observed in some patients with cancer.


T-cell leukemia with thymic involution.

T-cell leukemia with thymic involution. The prognosis of acute lymphoblastic leukemia is affected adversely by T-cell markers on the malignant lymphoblasts. Direct involvement of the thymus has been assumed because of frequent mediastinal enlargement in these patients and the important role of the thymus in certain mouse leukemias. We report here an adult with T-cell leukemia and mediastinal enlargement who had physiologic involution of the thymus. The possible role of diphenylhydantoin in the pathogenesis of this disease is reviewed. The possible usefulness of Nu/Nu mouse xenografting for the study of this lethal disorder is discussed.


Cytokinetic comparison of thymidine and leucovorin rescue of marrow in humans after exposure to high-dose methotrexate. The cytokinetics of marrow recovery were compared in patients receiving a standard exposure to high-dose methotrexate followed by either thymidine rescue, leucovorin rescue at the doses used in most clinical protocols (10 mg/sq m every 6 hr), or leucovorin rescue at a 5-fold higher dose rate (50 mg/sq m every 6 hr). Thymidine rescue initiated a prompt recovery of DNA synthesis, as detected by [3H]deoxycytidine incorporation, and progression of cells through the cell cycle monitored by flow cytometry, even in the presence of methotrexate levels that prevented initiation of rescue by the lower doses of leucovorin. Dose dependency for leucovorin in vivo in humans was suggested by the observation that the higher leucovorin dose rate was successful in initiating recue within the first 24 hr, whereas the lower dose was not. Recovery of DNA synthesis is more rapid and/or complete with thymidine rescue than with either dose of leucovorin. Thymidine rescue was accomplished without requirement for purines over and above those present in plasma. These results suggest that the kinetics of marrow recovery is quite different for thymidine and leucovorin rescue.


Vincristine effect on methotrexate cerebrospinal fluid concentration. A 67-year-old man with malignant lymphoma, nodular, poorly differentiated lymphocytic type, developed meningeal lymphomatosis. Repeated high-dose methotrexate-citrovorum factor treatment (1 g/m2 in 24 hours) rendered the patient free of disease. The administration of vincristine at 23 hours consistently increased the concentration of methotrexate in the cerebrospinal fluid 2.5-fold above baseline values.


Differential diagnosis of early opacification of the portal vein and its tributaries during arteriography. Twenty-two cases with communication of an artery and the portal vein or one of its tributaries are discussed. Four conditions in which relatively significant arterio-portal shunts may exist can be differentiated: (1) angiodysplasias or arteriovenous malformations, (2) cirrhosis of the liver and inflammatory lesions, (3) traumatic and postoperative lesions, and (4) benign and malignant tumors. The significance of the portal vein's early opacification during arteriographic examinations of the abdominal organs is discussed, and the findings are compared to those reported in the literature.


Catheter dislodgement: a cause of failure of intraarterial vasopressin infusions to control gastrointestinal bleeding. Catheter dislodgement is a major cause of technical failures in intraarterial vasopressin therapy for gastrointestinal bleeding. Ten such cases were observed in the past five years. In seven patients catheter dislodgement led to recurrent bleeding during vasopressin infusion. In one patient aortic infusion of vasopressin caused recurrent bleeding and reversible acrocyanosis of the feet, and in two patients vasopressin infusion into the left renal artery resulted in chest pain and hematuria. Catheter dislodgement should be suspected if bleeding that was initially controlled recurs during vasopressin infusion.


The early radiologic findings in the adult chest after cardiopulmonary bypass surgery. Postoperative chest radiographs of 70 adults who had undergone cardiopulmonary bypass surgery were evaluated. The distribution of pulmonary collapse/consolidation and pleural effusions, and the pattern of radiopacities related to drainage tubes were considered. Radiologic manifestations related to sternotomy were noted. Cases with a recorded postoperative blood loss of more than 280 ml/hour and/or an increase in mediastinal width of more than 70% had massive mediastinal hemorrhage that required reoperation. Changes in mediastinal contour were inconsistent, although total loss of mediastinal definition suggested hemorrhage or drainage tube blockage. A left apical extrapleural cap indicated massive mediastinal hemorrhage.


The behavior of collateral circulation after coronary artery bypass surgery. The changes in coronary collateral circulation after bypass surgery were analyzed in 50 patients with coronary disease. The demonstration of collateral circulation was found to be dependent upon the severity of the coronary heart disease and the patency of the bypass. When the graft was patent, it was usually not possible to visualize the collateral circulation demonstrated preoperatively. When the bypass was occluded, the same collateral circulation as before surgery was frequently found.


Efferent connections from the brain to the frontal organ in Rana temporaria demonstrated by labeling with horseradish peroxidase. After injection of horseradish peroxidase into the frontal organ of Rana temporaria, labeled perikarya were found in the medial part of the amygdala, the preoptic area, the nucleus rotundus, the pretectal area, and the lateral parts of the midbrain central griseum.


Angiodysplasia of the colon: a cause of rectal bleeding. Colonic angiodysplasia is a vascular lesion of the colon that may become the source of low grade chronic or intermittently massive rectal bleeding. It is a lesion of the elderly, almost always found in the cecum and the ascending colon. Etiology and pathogenesis are unknown. The diagnosis can be made with angiography based on the demonstration of a vascular tuft and early opacification of draining veins. Right hemicolectomy is the mode of therapy. The lesions are minute, and in resected specimens they can be found only with special vessel injection techniques. Histologically, the lesions represent clusters of dilated vessels, mostly veins, in the mucosa and submucosa of the cecum and ascending colon.


Comparison of vaccination of mice and rats with Haemophilus influenzae and Bordetella pertussis as models of atopy. 1. Rats and mice were vaccinated with Haemophilus influenzae in different vaccination schedules whereafter blood eosinophils were counted. In rats a single vaccination resulted in a dose-dependent effect on the blood eosinophil count in a pattern comparable with that after Bordetella pertussis vaccination. In a long-term vaccination schedule (five times a week for 5 weeks) rats developed a constant eosinophilia. In mice a single vaccination resulted in an eosinopenia of a consistent pattern which differed from the response after Bordetella pertussis vaccination; in a long-term vaccination schedule, eosinophilia was evoked for a period of about 13 days. 2. Thirty minutes after an adrenaline injection in vaccinated rats and mice with Haemophilus influenzae, hyperglycaemic and eosinophilic responses were measured. The eosinophilic response after adrenaline was inhibited in both species; the hyperglycaemic response in rats was unaltered, in mice the response was slightly but significantly (P less than 0.05) decreased. 3. The sensitivity to several drugs was tested in mice, 5 days after vaccination with Haemophilus influenzae or Bordetella pertussis. Haemophilus influenzae vaccination reduced the isoprenaline sensitivity and increased the noradrenaline sensitivity. Bordetella pertussis vaccination reduced the isoprenaline sensitivity while the sensitivity to histamine and adrenaline was raised. 4. The Haemophilus influenzae vaccinated experimental animal provides a model that is possibly more related to human atopy than the Bordetella pertussis vaccinated animal.


Value of computerized tomography scanning in syndromes associated with mental retardation: preliminary report. The application of CT scanning in the evaluation of mental retardation syndromes is reviewed. In a representative sample of 35 institutionalized patients, the CT scan showed gross anatomic abnormality in most. However, these findings were diagnostic in only a small minority. Implications of this are discussed. In addition, the potential role of CT in the diagnosis of intercurrent diseases in the mentally retarded is considered.


Recent trends in the immunology of contact sensitivity. I. The article reviews the recent experimental data that influenced the present concept of contact sensitivity. Particular emphasis is on the mechanism of stimulation of antigen-inexperienced specific lymphocytes, the eliciting phase, and the role of suppressor cells in sensitization and tolerance.


The development of the upper end of the femur in multiple hereditary exostosis. A roentgenographic study of 50 hips suggests that an increased anteversion-valgus configuration of the upper end of the femur is an intrinsic component and common in multiple hereditary exostosis. In one 8-year-old girl, the increased anteversion-valgus may have accelerated dislocation of a septic arthritic hip.


Diffuse neonatal hemangiomatosis. A case with heart failure and thrombocytopenia. An examination of the skin in a nine day old infant revealed multiple cherry-red superficial hemangiomas, which progressively increased in size and number. At the age of three weeks these skin lesions involved the scalp, trunk, extremities, palms, soles, and buccal mucous membranes. In addition, similar lesions of the liver and gastrointestinal tract were found. Steroids and irradiation were tried with limited success. Finally, hepatic artery ligation was successful in eliminating the heart failure.


Infected saphenous vein coronary artery bypass graft with mycotic aneurysm. Fatal dehiscence of the proximal anastomosis. A 33-year-old man underwent coronary artery bypass graft surgery for relief of angina pectoris. His postoperative course was complicated by hemorrhage and mediastinitis. Death, which occurred after severe hemorrhage from the operative site, was shown at autopsy to be caused by dehiscence of the proximal anastomosis of the right coronary artery graft. The same graft also had a mycotic aneurysm in its midportion. Graft disruption thus appears to be a potential complication of mediastinal infection in patients with saphenous vein bypass grafts.


A severe, stable obstructive defect in the airways in primary pulmonary histiocytosis X. An adult with biopsy-proven primary pulmonary histiocytosis X was followed-up over a period of 8 1/2 years. A severe obstructive defect was manifested by severely reduced rates of flow, a fall in the forced vital capacity from 2.6 L to 1.4 L, and a total lung capacity greater than 100 percent of the predicted normal value on three occasions. The patient has survived two episodes of respiratory failure. Her severe interstitial process may explain the development of obstruction of the airways.


The detection of perioperative myocardial infarction in aortocoronary bypass surgery. The incidence of myocardial infarction associated with aortocoronary bypass is difficult to determine because of widespread disagreement in evaluating the criteria for its detection. A prospective study consisting of 100 consecutive patients undergoing surgery for aortocoronary bypass was initiated. All patients were evaluated before and after surgery with electrocardiograms, heart scans of the infarct, and determinations of the level of the MB isoenzyme of creatine phosphokinase. A figure determined to be the upper limit of the expected rise in the level of the isoenzyme resulting from cardiac manipulation was selected, and 20 percent of the patients had more than the expected rise in the enzymatic level. Approximately one-half of these patients had abnormal ECGs or scans (or both) as well. The determination of the level of isoenzyme is very sensitive, and a normal level would exclude infarction. Elevations of concentrations of the enzyme due to minor myocardial cellular alterations are frequent. For this reason, in addition to an elevation of the concentration of the enzyme above the expected rise, the presence of an abnormal scan or ECG (or both) is necessary to make the diagnosis of perioperative infarction.


Function of lymphocytes and monocytes in silicosis. The function of lymphocytes and monocytes was compared in a group of 18 ex-sandblasters with silicosis and 19 control subjects. Previously noted depressed lymphocytic proliferation in response to low concentrations of concanavalin A (ConA) in subjects with silicosis was not due to factors in the serum nor correctable by supplementation with allogeneic lymphocytes. Monocytes from the peripheral blood of the subjects with silicosis responded less to a chemotactic stimulus (zymosan-activated serum) than did monocytes from normal laboratory personnel; however, there was no difference in monocytic chemotaxis when groups of similar age were compared. There was a significant correlation between age and the monocytic response to chemotactic stimuli in the studied population (laboratory personnel, silicotic subjects, and age-matched control subjects). Overall, our data suggest subtle effects of silica on selected T-lymphocytic populations involved with responsiveness to the mitogen, concanavalin A, but no effects on monocytic function. Monocytic chemotaxis is unaffected by exposure to silica but is inversely related to age.


Effects of indoleamines and their newly identified metabolites on prolactin release in rats. Plasma immunoreactive PRL responses to indoleamines and their metabolites were studied in urethane-anesthetized rats. All drugs were injected into the lateral ventricle and blood samples were serially collected from a jugular vein. Serotonin and melatonin caused a significant increase in plasma PRL with peak values at 10-20 min after the injection. Significant increase in plasma PRL were also observed after the administration of 5-hydroxykynurenamine (5-HK), a newly identified serotonin metabolite. The potency of 5-HK was less than that of serotonin but much greater than that of melatonin. In contrast, plasma PRL did not change significantly in response to N-acetyl-5-methoxykynurenamine, another newly identified metabolite of melatonin, or a vehicle solution. Simultaneous administration of melatonin significantly blunted the plasma PRL response to serotonin, whereas the rise in plasma PRL induced by 5-HK was not blunted by melatonin. These results suggest that indoleamines as well as their metabolites play a role in regulating PRL secretion in rats.


The effects of the epidermal and fibroblast growth factors on the replicative lifespan of cultured bovine granulosa cells. The effects of fibroblast growth factor (FGF) and epidermal growth factor (EGF) on the lifespan of cultured bovine granulosa cell cultures have been investigated. Granulosa cell cultures from small follicles (4-7 mm) had a lifespan of 11-12 generations, whereas the lifespan of cultures originating from large follicles did not exceed seven generations. The addition of either EGF or FGF to the medium of cultures originating from small follicles greatly increased the lifetime of the cultures, which can then exceed 60 generations. A similar, although less pronounced, effect was observed with cultures originating from large follicles. The lifespan of granulosa cell cultures depends upon the presence of FGF or EGF in the medium, as the deletion of the mitogens resulted in rapid terminal differentiation and a shortened replicative lifespan. As either FGF or EGF can prolong the replicative lifespan of granulosa cell cultures, it is suggested that limited replicative lifespan when maintained in the absence of mitogens is not so much determined by a fixed rate of mutation as it is by the culture conditions in which the cells are maintained.


Elevation of serum prolactin levels after the inhibition of serotonin uptake. Although earlier investigators showed that serotonin produced an elevation in serum PRL, recent studies indicate that serotonergic mechanisms are not of importance, at least in older adult animals, in the tonic regulation of serum PRL levels. As the activity of neuronal pathways may vary in activity at different chronological ages, the present study was undertaken to further evaluate the role of serotonergic pathways in the regulation of serum PRL levels. During the course of the study, animals in two different weight ranges were studied. In the initial studies, young male rats in the 120- to 170-g range were studied, while in later studies male rats in the 250-340-g weight range were utilized. In rats weighing 120-170 g, the administration of fluoxetine (Lilly 110140), an inhibitor of serotonin uptake, produced a significant elevation of serum PRL which persisted for at least 8 h. At the same time, diencephalon 5-hydroxyindoleacetic acid levels were decreased, providing evidence of the effectiveness of the drug treatment. Methysergide completely blocked the effect of fluoxetine and markedly suppressed serum PRL concentration. In agreement with the results of others, fluoxetine did not produce an increase in serum PRL in older male rats (250-340 g). However, fluoxetine seemed to suppress the circadian elevation of serum PRL in these older rats. These data provide evidence that serotonergic pathways may be of more importance in the tonic regulation of serum PRL in young male Sprague-Dawley rats. The specific pathways involved cannot be determined from these studies.


Modification of DNA in chromatin with methyltransferase from Haemophilus influenzae Rd. The accessibility of DNA in nucleosome dimers (as a model of the chromosomal chain of nucleosomes) was determined by means of modification methylases from Haemophilus influenzae Rd. Using these enzymes, the rate of modification of nucleosome dimers is about one fifth the rate observed with protein-free DNA from chromatin subunit dimers. Methylated DNA sites in nucleosome dimers are readily accessible to micrococcal nuclease. The analysis of the fragment pattern of nucleosomes after methylation and mild nuclease treatment reveals that the methylated sites are predominantly located in the internucleosomal linker DNA. Polylysine binding experiments further support this interpretation. This compound preferentially interacts with the nucleosomal core DNA and protects it against internal cleavage. It neither affects the degradation of methylated sites drastically nor does it inhibit the methylation of nucleosome dimers. Thus, a combination of protection, cleavage and modification is proposed as a useful tool for the analysis of the structure of chromatin.


Defective neutrophil chemotaxis and bactericidal power in a child with hyperimmunoglobulinemia E. An 11-year-old boy with a life-long history of atopic-like dermatitis and recurrent staphylococcal abscesses was found to have defective neutrophil chemotaxis, impaired-T-lymphocyte functions, hyperimmunoglobulinemia E, and delayed neutrophil bactericidal power. This latter defect has never been found in such patients. The patient's mother revealed a panhypogammaglobulinemia, while his sister and maternal grandmother who had repeated infections were immunologically normal.


Immune evaluation with skin tests in prostatic carcinoma. By intradermal injection of 3 recall antigens, nonspecific secondary cell immunity was studied in 61 patients with prostatic carcinomas. Immune competence is lower in patients with metastatic disease. Skin tests have a short-term prognostical value.


Exercise ECG in evaluation of aortocoronary bypass surgery; report on 66 patients. To evaluate the relationship of functional results after aortocoronary saphenous bypass surgery, 66 patients of age 33--65 yr (mean 52) underwent a standarized bicycle exercise test before and an average of 14 mth after operation. Capacity of exercise was correlated with symptomatic response and graft patency. Group exercise tolerance was significantly improved after operation, and was about 60% of that of a population-based series of 52-yr-old men [6]. After operation 74% of the patients could exercise to fatigue without apparent limiting cardiac symptoms, while 26% still were incapacitated because of angina. Improvement in tolerance for exercise correlated with symptomatic improvement as well as patency of the grafts; patients with no grafts remaining patent showed no improvement in exercise performance.


Transient left anterior hemiblock during angina pectoris: coronarographic aspects and clinical significance. The data of 6 patients in whom a left anterior hemiblock appeared in the course of angina pectoris attacks were reviewed. All 6 patients were found to fulfill the criteria for unstable angina. 1 patient who presented the features of Prinzmetal variant angina was included in this group. Coronary arteriography showed significant coronary artery disease in all 6 patients involving 3 vessels in 2 patients, 2 vessels in 1 and 1 vessel in 3. A severe lesion (70--100%) of the left anterior descending artery in the vicinity of the first perforator was demonstrated in every case. The 2 patients with 3-vessel disease were not operable and died 4 and 5 days after the hemodynamic study. These deaths were caused by myocardial infarction with cardiogenic shock in one case and intractable ventricular arrhythmias in the other case. 4 patients were operable and underwent aortocoronary saphenous bypass surgery. There were 2 operative deaths. The 2 survivors are asymptomatic 7 and 16 mth after surgery. This study suggest that transient left anterior hemiblock during an attack of angina pectoris may be a feature of impending myocardial infarction and may be indicative of a severe obstruction of the left anterior descending coronary artery.


Granulopoietic increase by BCG in mice.

Granulopoietic increase by BCG in mice. Repeated doses of the non-specific immunostimulant BCG were injected intraperitoneally, followed by serial measurement of serum colony stimulating factor (CSF), and CFU-C number and percent synthesizing DNA. Following primary challenge with BCG, CSF remained at low levels until day 7, rose to a peak by day 10, and remained elevated through 14 days. Secondary challenge resulted in a bi-phasic CSF response with a small peak on day 1 and a larger one by day 7. Following secondary challenge, the percent of CFU-C in 'S' phase doubled in 24 hours; CFU-C significantly increased in number by 48 hours. The studies suggest that the marrow toxicity of cycle active cytotoxic drugs might be altered by non-specific immunostimulants such as BCG.


Distribution of retinal axons within the lateral hypothalamic area. Intraocular injections of tritiated leucine were performed in normal and in unilaterally enucleated adult albino rats. Light microscopical evaluation of the autoradiograms revealed evidence for retinal afferents to distribute within a rather circumscribed area of the lateral hypothalamus. The silver grains were consistently, however, observed only in the group of enucleated animals, indicating differential transport under basic and experimental conditions.


Diencephalic binocular wide field neurons in the frog. Single binocular neurons were recorded in the frog diencephalon (area dorsalis posterior and area ventralis thalami). These neurons respond to any moving stimulus from 1 degree 30 to 32 degrees in diameter, without directional selectivity and to an ON-OFF light stimulation. They are not activated by stationary objects. Habituation is also commonly observed. The most important feature of these neurons is their wide receptive field which covers the whole visual field of the frog. Evidence that these neurons receive inputs from each tectum is discussed.


Satellite cells in denervated muscles.

Satellite cells in denervated muscles. It is known that, in a denervated striated muscle, the satellite cells multiply by mitotic division. A liaison between these satellite cells and the Schwann cell in front of the post-synaptic membrane in denervated frog muscle has been observed. It is probable that such cell connections help in the subsistence of the Schwann cell in a denervated muscle.


Laser Doppler microscope in an oblique-backward mode and pulsatile blood flow velocity in pulmonary arteriole. Blood flow velocity, pulsatile in correspondence to cardiac events, in pulmonary arterioles of anesthetized bullfrogs could be measured on lung surfaces covered with a water-containing plastic disc by means of a laser Droppler microscope arranged in an oblique-backward mode.


Alkaline phosphatase in human lymphocyte subpopulations. The levels of membrane alkaline phosphatase have been measured on different lymphocyte fractions from human peripheral blood separated on bovine serum albumin discontinuous gradients. The peak in enzyme activity was observed in a non-T-, non-B-cell fraction, rich in "null" lymphocytes; the lowest values were found in the fraction with the highest proportion of T-cells.


[Chemical and pharmaceutical research on pyran derivatives. X. Synthesis of 1-oxo-2-alkyl-3-dialkylamino-1H-naphtho[2,1b]pyrans]. When reaction of N,N-dialkyl-alpha-ethoxycarbonyl-alpha-alkylacetamides with beta-naphthol in the presence of phosphorus oxychloride was carried out in chlorobenzene at reflux, formation of 1-oxo-2-alkyl-3-dialkyl-amino-1H-naphtho[2,1-b]pyrans was achieved together with some other products whose structure was defined. Moreover, substitution of the 2 position of 1-oxo-3-dialkylamino-1H"naphtho[2,1-b]pyrans with chlorine or cyano group as well as the preparation of 1-thio-3-dialkylamino-1H-naphtho[2,1-b]pyrans was obtained by suitable chemical methods. Pharmacological screening of these compounds showed the lack of psychotropic activity of the corresponding 1-oxo-3-dialkylamino-1H-naphtho[2,1-b]pyrans.


[Synthesis and pharmacologic activity of benzothiopyranopyrazole and benzothiopyranoisoxazole carboxamides]. A series of carboxamides of benzotiopyranopyrazoles and benzothiiopyranoisoxazoles was synthesized starting from benzothiopyran-4-one-3-methylglyoxylates through two synthetic methods and tested for anti-inflammatory, analgesic and cardiovascular activity. Some of these compounds display pronounced antiarrhythmic activity.


[Synthesis of 2,6-substituted derivatives of 5H-1.3.4-thiadiazolo[3,2a]-s-triazine-5,7-dione]. The synthesis of derivatives of 5H-1,3,4-thiadiazolo[3,2-a]-s-triazine-5,7-dione substituted in position 2 and 6 is described. The compounds were subjected to pharmacological screening, and some were found to possess antiinflammatory and antipyretic properties.


Diflunisal, a new-acting analgesic and prostaglandin inhibitor: effect of concomitant acetylsalicylic acid therapy on ototoxicity and on disposition of both drugs. Intermittent and concomitant acetylsalicylic acid (ASA) therapy was superimposed onto a 21-day regimen with diflunisal 250 mg b.i.d. Low doses of ASA (600 mg single dose or 300 mg q.i.d.) did not influence signficantly diflunisal blood levels whereas a 600 mg q.i.d. dosing caused a small significant drop, especially at trough level. This drop is not expected to be clinically significant. No ototoxicity could be demonstrated with any treatment of diflunisal though four of fourteen subjects reported mild tinnitus during concomitant therapy at the higher doses of ASA. Diflunisal at 375 mg b.i.d. failed to alter the metabolism of a single dose of labelled ASA (600 mg) as judged by plasma levels, urinary excretion and plasma binding. Daily urinary excretion of prostaglandins E1 and E2 major metabolite was decreased by about 70% by diflunisal.


[Pregnancy after portocaval shunt operation. A case of report and review of the literature (author's transl)]. Acute variceal haemorrhage due to portal hypertension in chronic liver disease is the most fatal maternal complication when pregnancy occurs. These risks can be avoided when a shuntoperation is performed before or during pregnancy. 26 cases of uncomplicated pregnancies after shuntoperations have been reported in the literature. Another one is added.


Mitogenicity of fetal calf serum.

Mitogenicity of fetal calf serum. The mitogenic effect of fetal calf serum (FCS) has been studied. Human lymphocytes, especially cord blood cells, undergo blastogenesis in media supplemented with FCS. The mitogenic effect is exerted on non-T (B and null) lymphocytes, but not on T cells. Bovine serum albumin (BSA) successfully substitutes for FCS in mitogen-induced lymphocyte blastogenesis. Unlike FCS, it has no mitogenic properties.


[Correlations between lymphocyte subpopulation and stage of disease in chronic lymphatic leukemia of Rai]. T- and B-lymphocytes have been studied in 36 patients with chronic lymphatic leukaemia (CLL). Each 12 cases remained untreated or were treated with chlorambucil or extracorporeal irradiation of the blood (ECIB). The patients were classified according to the staging system proposed by Rai et al. In all groups we found significantly elevated B- and T-cells. There was no correlation between the stage of the disease and the proportion of lymphocytes. B-lymphocytes were reduced significantly by ECIB, whereas T-lymphocytes have not been influenced.


II. Mechanism of increased colony formation of CFU-S and CFU-C after in vivo PHA administration in mice. In vivo administration of 3 mg PHA-M results in an increase in spleen colonies due to an augmented seeding of CFU-S into the spleen. An increase in the number of CFU-S in the developing nine-day spleen colonies also occurred together with a slight increase in the number of CFU-S in DNA-S phase 24 hours after PHA-M administration. The increased colony formation was due to an increased number of CFU-C from the early culture period onwards but could not be explained by an increase in the number of CFU-C in DNA/S phase. The release of colony-stimulating substances was proved but this only partially accounted for the observed rise in bone marrow CFU-C.


[Coronary collaterals and function of the left ventricle. Practical applications of a collateral score]. The most important collateral pathways in the coronary artery system goes through the apex, the ventricular septum, left and right atrial branches and the ventricular wall of the left ventricle. In a collective of 52 patients who underwent aortocoronary-bypass surgery we controlled the collateral circulation and left ventricle function. Patients with multiple-vessel-disease had in 71% good collateral circulation and the collateral score was more than twice as high as in patients with one-vessel-disease. In addition we compared the LVEDP in these 52 operated patients and in 52, whose condition did not permit coronary surgery. The enddiastolic pressure is lower in patients with good collaterals and was also better in patients who underwent surgery.


[Ecogenetics].

[Ecogenetics]. Some examples of ecogenetics--including pharmacogenetics--demonstrate the tremendous variability in genetic constitution within a population as well as between different populations. They are the reason for different atypical responses to xenobiotics, synthetics like drugs, pesticides, insecticides, herbicides, industrial irritation, smog, cigarettes, alcohol, as well as naturally occurring substances like aflatoxines. It is unknown to what extent individuals differ in their susceptibilities and which genetic consequences of exposure of the human population to toxic environmental agents will occur. It is referred to genetic traits causing a predisposition for atypical reactions against chemicals of different structure as well as to the mutagenic and inductive action of such compounds. In this connection, population genetic aspects will be considered. All examples have to be seen in the context of ecogenetics, the genetically determined individual differences in adverse responses to environmental pollutants, and they are of special interest for preventive and industrial medicine.


[Multiple sclerosis in computer tomography of the brain (author's transl)]. Tissue changes were examined in detail via computerised tomography (matrix 160 X 160) in 28 patients with neurologically established encephalomyelitis disseminata. In the majority of cases, demyelinisation was not characteristic of the predominant pathologico-anatomical substrate, ventricular extension with diffuse atrophy but without demyelinisation being the leading sign. However, if the disseminated disease became manifest with foci of demyelinisation, these presented a preferably periventricular pattern.


Computer analysis of defined populations of lymphocytes irradiated in vitro. III. Evaluation of human T and B cells of peripheral blood origin. The radiosensitivities of lymphocytes of peripheral blood origin obtained from two healthy 45 year old male donors were studied simultaneously at yearly intervals over a three year period. Hypaque-Ficoll purified cells were exposed in vitro to 0, 5, 50, and 500 rads and then evaluated serially for viability of T and B cells, responsiveness to PHA and Con A, and morphologic evidence of injury as documented by standard light microscopy and computer assisted morphometric analysis. The results showed that T cells in both subjects were less radiosensitive than B cells. Differences between the two subjects also existed in the radiosensitivity of these two subpopulations of lymphocytes, differences that remained constant over the three years period of observation. The differences correlated with similar discrepancies in mitogenic responsiveness and are thought to relate to variations in the relative proportions of subpopulations of T and B cells. In the mouse, T and B cell subpopulations differ in radiosensitivity. The data reported herein are consistent with a similar situation in man.


An improved micro-method for enumeration of human B-cell rosettes with mouse red blood cells. A micro-method for enumerating B-lymphocytes in human peripheral blood is described, using formation of rosettes with mouse red blood cells as a B-cell marker. The optimal conditions for the enumeration of mouse red cell rosette forming cells have been defined. By this method, it was possible to utilize less than 1ml of peripheral blood (venous or capillary) for simultaneous enumeration of both T-cell and B-cell rosettes. Our study of human lymphoid cell lines, thymic cells, lymphocytes from agammaglobulinemia, and severe combined immunodeficiency has provided additional evidence that lymphocyte rosetting with mouse red blood cells represent B-lymphocytes.


Isolation of human T lymphocytes by a negative selection procedure. A single step method to isolate human T lymphocytes was achieved using a rosette technique to deplete non-T lymphocytes. Erythrocytes coated simultaneously with IgG and complement were used to form rosettes with cells bearing such receptors during a short incubation period and the rosetting cells removed by gradient centrifugation. T lymphocytes were isolated (greater than 96% T cells) without exposing to much experimental manipulations and in good recovery (mean 60%, range 40-75%).


Enhancement by muramyl dipeptide of in vitro nude mice responses to a T-dependent antigen. N-acetyl-muramyl-L-alanyl-D-isoglutamine (referred to as MDP for muramyl dipeptide) has been shown to enhance in vivo and in vitro immune responses to various antigens. It has previously been reported that in the case of T-dependent antigens, the adjuvant activity of MDP was mediated by a helper T-cell. Our present findings demonstrate that in vitro responses of nude mice spleen cells to T-independent, TNP-PAA or T-dependent SRBC can also be markedly increased by this synthetic adjuvant. Moreover, under the same conditions, MDP produced polyclonal activation.


Sera from volunteers immunized by planned blood transfusions as source of DR cytotoxic typing reagents. Sera from volunteers immunized with planned blood transfusions were tested for anti DR cytotoxic antibodies with a panel of HLA typed cultured human lymphoid cells using a variety of serological techniques. The majority of sera contained DR cytotoxic antibodies. The specificity of DR antibodies in seven sera was determined by testing them with a panel of B peripheral lymphocytes typed with DR alloantisera submitted to the 7th International Histocompatibility Workshop. The temporal evolution of DR and HLA-A and B cytotoxic antibodies was determined in two subjects by testing serial bleedings with B lymphoid cells, coated with Fab2 fragments from anti beta 2 mu and anti DR xenoantisera. Results indicated a parallel evolution of DR and HLA-A and B cytotoxic antibodies.


The mechanism of T-cell mediated cytotoxicity. VI. T-cell projections and their role in target cell killing. Electron micrographs of material fixed during the first 10 min of a T-cell cytotoxic system showed T-cell projections and T-cell burrowing into target cells. These observations were made possible by using a system with a very high rate of killing. The projections vary in shape and size, and can push deeply into the target cell, distorting organelles in their path, including the nucleus. The projections contain fine fibrillar material, to the exclusion of organelles. They push the target cell membrane in front of them to form pockets approximating to the shape of the projection. Areas of close contact occur between the projections and the target cell membrane, particularly at the leading edges. The likelihood that these projections develop as a result of contact with specific antigen, and are involved in the cytotoxic mechanism is discussed.


The influence of antigen dose on IgE production in different rat strains. Strain differences in total serum IgE levels and IgE antibody responses to various amounts of antigen were studied in rats. Five inbred strains (BN, Wistar R/A, DA, LEW, PVG), (Wistar R/A x BN)F1 and (LEW x BN) F1 hybrids were immunized twice at an interval of 28 days by intraperitoneal injection of 10 ng, 100 ng, 1 microgram, 10 microgram, 100 microgram or 1 mg ovalbumin and 1 mg A1(OH)3 in a volume of 0.5 ml. Total serum IgE and IgE antibody levels were followed. Both parameters were measured with a solid phase radioimmunoassay. A significant difference was observed in total IgE levels between the different strains. The IgE antibody response depended both on the strain and on the amount of antigen used for immunization. There was an optimal antigen dose for IgE antibody formation, differing from strain to strain. F1 hybrids had total IgE levels and IgE responses intermediary between those of the two parent strains. A good correlation existed between the total serum IgE level before immunization and the magnitude of the optimum IgE antibody responses in the different strains. These results suggest that there may be a genetic influence on both parameters, the total IgE level and the specific IgE antibody response. The IgE antibody response is also dependent on the dose of antigen.


Guinea-pig lymphotoxin resistant L-cell sublines. Guinea-pig lymphotoxin (GLT)-resistant L-cell sublines were isolated, and the altered properties were characterized. Two of them (No. 1 and No. 2 cells) showed the lowest capacity to absorb GLT and substantially reduced ability to bind labelled Ricinus communis agglutinin (RcA). Both the cell-surface proteins and glycoproteins of No. 2 cells were found to be quite different from those of parental L cells. The glycoprotein of molecular weight 140,000, which specifically bound to RcA-Sepharose, was missing in the No. 2 cells extract. These results indicate that the glycoprotein of molecular weight 140,000 is the most probable candidate for the receptor molecule for GLT, and that No. 2 cells and probably No. 1 cells are GLT receptor-deficient cells.


Cellular immunity against Semliki Forest virus in mice. Intracutaneous immunization of BALB/c mice with purified inactivated Semliki Forest virus resulted in cellular immunity without detectable antibodies. The animals were protected against subcutaneous challenge, from which the challenge virus spreads slowly. After intraperitoneal challenge, which permits a rapid virus spread, the protection was marginal. Stimulation of the intraperitoneal cell population with thioglycolate before challenge resulted in complete protection. The protection could be transferred to normal mice with peripheral lymph node cells, but not with spleen cells. The course of the infection in immunized and normal mice was also studied. Semliki Forest virus does not multiply in peritoneal cells in vivo. In immunized mice part of the challenge virus in the peritoneal cavity was rapidly eliminated and viremia was reduced. After challenge, immunized mice produced less antibody than normal mice.


Splenomegaly in murine trypanosomiasis: T cell-dependent phenomenon. Splenomegaly resulting from Trypanosoma musculi infection was found to be dependent upon a functioning T-lymphocyte system. When both humoral and cell-mediated immune systems were suppressed by treatment with cyclophosphamide 2 days after infection, splenomegaly was inhibited for about 6 days. However, when only humoral immunity was suppressed by treatment with cyclophosphamide 3 days before infection, splenomegaly still occurred. In addition, splenomegaly was absent in congenitally athymic nude mice. Nude mice and immunologically intact heterozygote mice were also sacrificed at varying times after infection, and spleens were examined histologically. A lymphocytic hyperplasia was observed in immunologically intact mice but not in nude mice. These data indicate that splenomegaly of T. musculi infections is T cell dependent and that splenomegaly is the result of a proliferation of B and/or T lymphocytes.


Stimulation of T-independent antibody responses by hapten-lipopolysaccharides without repeating polymeric structure. The murine immune response to a haptenated lipopolysaccharide (LPS) lacking repeating oligosaccharide determinants was studied. The LPS was extracted from a rough strain of bacteria (Salmonella minnesota R595) and chemically haptenated with either trinitrophenol or fluorescein isothiocyanate. These preparations of hapten-R595 LPS were shown to be immunogenic. Furthermore, the immune response to the hapten was demonstrated to occur independent of T cells and was not merely the result of enhanced polyclonal B-cell activation. The capacity of such hapten-LPS conjugates without repeating polymeric structures to stimulate T-independent antibody responses provides information on the molecular requirements for the activation of murine B lymphocytes.


Interactions between immune cells and antibody in protection from fatal Sindbis virus encephalitis. Transfer of anti-Sindbis virus serum, obtained from peripherally inoculated donors, protected mice from an otherwise fatal intracerebral infection with neuroadapted Sindbis virus (NSV). F(ab)'2 preparations of serum were not protective, indicating that the Fc piece of immunoglobulin G was important. Complement-depleted animals were protected with anti-NSV serum, ruling out as essential the complement-fixing function of the Fc piece. The presence of protective antibody correlated with the ability of serum to inhibit T-cell cytotoxicity. However, experiments using athymic nude mice showed that T cells played no role in killing the mice since the 50% lethal dose was the same as that in normal BALB/c mice, and that T cells were not required for protection since athymic nude mice were protected with antibody alone. Cyclophosphamide treatment of NSV-infected mice ablated the protective capacity of anti-NSV serum. Therefore, a non-T cell, cyclophosphamide-sensitive cell was required for antibody-mediated protection.


Cell-mediated immune response to bacterial products in human tonsils and peripheral blood lymphocytes. Lymphoproliferative responses of tonsillar tissue lymphocytes and peripheral blood lymphocytes to phytohemagglutinin and specific bacterial product antigens were studied in children undergoing tonsillectomy and adenoidectomy. Tonsillar tissue lymphocytes responded to optimal concentrations of phytohemagglutinin. Varidase, and streptolysin-O in a manner similar to peripheral blood lymphocytes. Higher base-line mitogenic activity in tonsillar lymphocytes was frequently associated with the presence of Staphylococcus aureus in the tonsils. Tonsillar tissue lymphocytes from 23% of the subjects with the highest base-line mitogenic activity manifested a decreased response to in vitro stimulation with mitogens or antigens. In subjects with such preactivated tonsillar lymphocytes, the proliferative responsiveness of blood lymphocytes to mitogen and antigens was markedly increased after tonsillectomy and adenoidectomy. These observations suggest the existence of in vitro correlates of cellular immunity to bacterial products in the mucosal surfaces. In addition, it is proposed that tonsils may possess immunosuppressive activity for peripheral blood lymphocytes, which may be related to local tonsillar infections.


Thymic dependence of immunity to Eimeria falciformis var. pragensis in mice. Athymic (nude) mice, their normal littermates, and Swiss white mice were infected with 750 oocysts of Eimeria falciformis var. pragensis and reinfected twice with 20,000 oocysts, 20 and 40 days after the primary infection. The prepatent and patent periods of the primary infection were similar in each group of mice; however, the athymic mice discharged more oocysts. The normal littermates and Swiss white mice developed immunity to the parasite after the first or second infection, whereas the athymic mice never developed immunity. Infection with E. falciformis var. pragensis induced the production of antibodies in the normal littermates and Swiss white mice, whereas antibody production was impaired in athymic mice. Passive administration of immune serum did not protect athymic mice from reinfection by the parasite. Immunity to the parasite was thymus dependent, and "effector" T-lymphocytes seemed to be required for protection.


Cooperative effects in mitogen- and antigen-induced responses of human peripheral blood lymphocyte subpopulations. Human peripheral blood lymphocytes were separated into T cell-enriched and T cell-depleted fractions by E rosette sedimentation. These two fractions, as well as the unseparated lymphocyte suspension, were tested for their responsiveness to the mitogens phytohemagglutinin (PHA), concanavalin A (ConA) and pokeweed mitogen (PWM) and to the antigens PPD (purified protein derivative of tuberculin) and tetanus toxoid. The response to PHA, ConA and the antigens was found to be confined to the purified T cell fraction; PWM could stimulate both purified T and non-T cells. However, the T cell response to ConA, PPD and tetanus toxoid was always decreased by 50-70%, when compared to the unseparated lymphocytes. Addition of monocytes could restore the T cell response. In the response to PHA and tetanus toxoid, the (primarily unresponsive) non-T cell fraction could be recruited into proliferation by gamma-irradiated T cells. Moreover, in the response to tetanus toxoid, lymphocytes (T as well as non-T) from a nonimmune individual could be recruited into proliferation by gamma-irradiated immune T cells.


Lymphocyte stimulation with phorbol myristate acetate in atopic and non-atopic individuals. Phorbol myristate acetate (PMA) was found to be a potent stimulator of DNA synthesis in human whole blood cell cultures. Stimulation with pokeweed mitogen was strongly enhanced by addition of PMA-activated cells. PMA responsiveness varied with age, being low or absent in newborns and very pronounced in adults. In atopic children, PMA responsiveness was normal or increased. The ratio of phytohemagglutinin to PMA responsiveness was significantly reduced in cultures from such children. This finding would be compatible with the hypothesis of a relative suppressor cell deficiency in atopic disease. The results of tests designed to detect suppressor and helper cell activity, added further support to this hypothesis.


Immunological studies in patients with alopecia areata. Cellular and humoral immune parameters were studied in 10 patients with alopecia areata totalis and universalis. Trends to low normal immunoglobulins levels and in vitro lymphocyte transformation to concanavalin A were observed. Serum CH-50 levels and skin test responses to mumps, candida, trichophytin and dinitrochlorobenzene (DNCB) not found in vitro. 1 patient with alopecia universalis of 33 years duration developed hair at the site of DNCB skin testing. The findings point to rather subtle immune defects in patients with this disease.


Alterations in granulation tissue growth induced in vivo by lymphocytes from adjuvant-diseased rats. Lymph node cells from Lewis and Wistar rats, treated 9 or 11 days previously with Freund's complete (FCA) or incomplete adjuvant (FIA), were transferred into polyether sponges implanted subcutaneously into syngeneic, recipient rats. FCA-treated lymphocytes enhanced or reduced granuloma formation (measured after 8 days), when compared with FIA-treated controls, depending on the strain of mycobacterium present in the FCA. The stimulatory effects of lymphocytes from FCA-treated, Lewis rats were abolished by pre-incubation with mitomycin C (25 microgram/ml). Whole serum and isolated serum immunoglobulin from adjuvant-diseased rats had no effect on the sponge granulomas. These data confirm that cell-mediated immunity is involved in the articular granuloma formation of adjuvant arthritis.


Sensitization of guinea pigs to levamisole. Levamisole, an anti-helminthic drug used also as an immunostimulating agent, has been found to be a potent skin sensitizer in experimental animal models. Sensitization is associated with marked T-lymphocyte proliferation in the draining lymph node. It is suggested that immunostimulation through increase in the T-lymphocyte population could be a function of the strong sensitization induced by this compound.


Delayed type hypersensitivity to allogeneic cells in mice. II. Cell transfer studies. Sensitivity to allogeneic cell surface antigens was transferred to naive mice by lymphoid cells from sensitized mice. Sensitivity was detected 24-48 h after antigen challenge and was associated with a mononuclear cell infiltration. The cells responsible for transfer were T lymphocytes as demonstrated by successful transfer with cell suspensions enriched for T lymphocytes, and by abrogation of transfer following treatment with anti-Thy-1.2 serum and complement. Both Lyl+ and Ly2+3+ bearing T cells were involved. Removal of Ia+ cells had no effect on the ability of sensitized lymphoid cells to transfer the reaction to naive mice.


Spectral studies on two genetic forms of the human serum proteinase inhibitor, alpha-1-antitrypsin. alpha-1-antitrypsin, the major inhibitor of proteolytic enzymes in human serum, was isolated from normal individuals (protease inhibitor type MM) and from those with an inherited deficiency (protease inhibitor type ZZ) of circulatory protein. The two proteins were compared by circular dichroism spectroscopy, and by fluorescence quenching experiments using anionic (I-), and neutral (acrylamide) probes. Both proteins share a similar secondary structure, i.e. approximately 45--50% alpha-helix and 15--20% beta-structure. Evidence was accumulated to show that the microenvironment in the vicinity of the three tryptophanyl residues is altered in Z form as compared to the M form as shown by (a) the absence of the positive dichroic band in the region 290--300 nm of the circular dichroism spectra, (b) a greater than 50% increase in quantum yield in the tryptophanyl fluorescence emission spectra, (c) an increased accessibility of tryptophan to quenching by iodide, and (d) acrylamide quenching experiments which indicate that all tryptophanyl residues in the Z protein are quenched equally or that quenching is dominated by a single residue, while in the M protein, heterogeneous quenching occurs. The potential significance of these findings in terms of alpha-1-antitrypsin deficiency state are discussed.


Intraocular levels of cefamandole compared with cefazolin after subconjunctival injection in rabbits. We compared the intraocular pharmacokinetics of cefazolin with those of cefamandole, a recently marketed cephalosporin with enhanced activity against gram-negative bacilli. Following subconjunctival injection of 12.5 mg into infected eyes (S. aureus endophthalmitis) of pigmented rabbits, both drugs reached peak concentrations greater than 100 microgram/gm in cornea, sclera, and choroid-retina. The half-life was markedly shorter in sclera and choroid-retina than in cornea. Levels in the aqueous humor rose and fell more slowly than those in ocular tissues, reaching a maximum of only 5 to 10 microgram/ml. The pharmacokinetics of the two drugs were virtually identical in most intraocular sites. When cefazolin, which was less irritating than cefamandole by the subconjunctival route, was given in a dosage of 100 mg, levels in ocular tissues were increased by twofold to fourfold and in aqueous humor by 15-fold, compared to the concentrations produced by the 12.5 mg dosage. Levels in the vitreous humor were exceedingly low with both drugs; mean peak concentrations were 0.24 microgram/ml after the 12.5 mg dosage of cefamandole and less than 1.6 microgram/ml after the 100 mg dose of cefazolin.


Immune competence assessment in hyperbilirubinemic newborns before and after phototherapy. Tests for immune competence in normal and hyperbilirubinemic newborns--before and after phototherapy--were assessed. The lymphoproliferative response to PHA-M in hyperbilirubinemic infants was inhibited in the presence of autologous plasma in comparison with normal infants and normal adults. The phototherapy does not seem to inhibit the lymphoproliferative response. After phototherapy, an increased level of IgM and a slight decrease in IgG concentration were found. These data support the possibility that phototherapy is not contraindicated during septic hyperbilirubinemia.


Modified chromogenic alpha-amylase assay for sprouted wheat. Sensitivity of a test in which a commercially available substrate was used for the assay of alpha-amylase in sprouted wheat has been increased by the use of optimally buffered (pH 6.20) Cibacron-Blue dyed amylose at 60 degrees C. With the modified test, measurable alpha-amylase levels were in the range of 3--30 millidextrinizing units (mDU) as compared to the 10--90 mDU range in a test previously reported for bread wheats. The modification extends the use of the test to evaluation of sprout damage in wheats used in the manufacture of Japanese noodles and sponge cakes.


Control of aldehyde synthesis in the luminous bacterium Beneckea harveyi. Some of the Beneckea harveyi dim aldehyde mutants, all of which emit light upon addition of exogenous long-chain aldehyde, also emit light when myristic acid is added. Analysis of these myristic acid-responsive mutants indicates that they are blocked before fatty acid formation, whereas another class of mutants, which respond only to aldehyde, appear to be defective in the enzyme(s) involved in the conversion of acid to aldehyde. Evidence is presented that this activity, designated myristic acid reductase, is coinduced with luciferase and is involved in the recycling of acid produced in the luciferase reaction, with specificity for the C14 compounds.


Approaches to reliability in a clinical simulation study. Discusses the reliability of measurements made by 48 raters who used the Problem Dysfunction Rating Scale (PDRS) under simulated routine clinical record-keeping conditions. Ten- to 15-minute videotape interviews of two simulated patients with predefined problems were shown to a multidisciplinary psychiatric hospital staff of varying educational background and clinical experience. These raters were given only brief instructions and no training in the use of the PDRS. Statistical analysis included application of the usual, traditional test and retest variation studies and used variance components and comparison to random rating models. A random contrast of rater agreement was found to index most realistically reliability in instances such as this, in which a large number of raters rate a small number of items. There was greater intrarater consistency than interrater agreement, and it was concluded that when reasonably adequate information was available the degree of dysfunction due to patients' problems could be rated on the PDRS with a useful degree of consistency by untrained raters.


Functional anatomy of the cerebral cortex by computed tomography. The authors describe the morphological characteristics that allow recognition of the individual computed tomography slice and determine its sequence in the series. In addition, each slices is "assembled" by defining the different cortical gyri, sulci, and cortical functional areas (based on Brodmann's maps). This work lays the foundation for correlative studies of location of lesions and the clinical picture.


Evaluation of a combination of self-administered fluoride procedures for the control of dental caries in a nonfluoride area: findings after four years. Nearly all children who attend elementary school (grades K through 6) in a rural community have participated since 1972 in a school-based caries preventive program consisting of daily ingestion of a 1-mg fluoride tablet and weekly rinsing with a 0.2% sodium fluoride solution. 3they also regularly receive toothbrushes and a fluoride dentifrice for use at home. Examinations conducted after four years showed that the prevalence of dental caries among continuous participants, 7 through 12 years of age, was reduced by 35% compared with baseline findings; mean DMFS scores in 1972 and 1976 were 5.39 and 3.49, respectively. The preventive program inhibited decay in all three types of surfaces: approximal surfaces received about twice the relative protection against decay (70%) as buccolingual surfaces (34%) and more than three times as much as occlusal surfaces (22%). A comparison of estimates of four-year increments of decay taken from cross-sectional data at the baseline and actual increments from the 1972 and 1976 examinations showed that, for children ages 6 through 15, the incremental DMFS score was 41% lower during the period of the program than before its initiation. Findings in older children (ages 13 through 15) in 1976 who had stopped participation when they left elementary school at about age 12 showed evidence of strong posttreatment effects--as great as 31% fewer DMFS for 14-year-old children.


Purification and testing of class-specific anti-chicken immunoglobulin antibodies. The purification and testing of chicken immunoglobulins and of class-specific antichicken immunoglobulin antibodies are described. This work suggests the existence of as yet uncharacterized classes of chicken immunoglobulins. Their eventual determination in a species that has a B lymphopoietic organ may promote further progress in the understanding of B cell differentiation and function.


Leukocyte migration inhibition factor in atopic dermatitis: induction by concanavalin A in vitro. Assays for the production of leukocyte migration inhibition factor (LMIF) activity by cultured lymphocytes in the presence of the T-cell mitogen concanavalin A (ConA) have been shown to be highly sensitive for detecting decreases in cell-mediated immunity in patients with malignant diseases and primary and secondary immunodeficiency diseases. We have applied the leukocyte migration inhibition test in agarose using supernatants from ConA-stimulated lymphocyte cultures (indirect leukocyte migration inhibition test in agarose for studying patients with atopic dermatitis. Only 5 of 14 lymphocyte cultures from atopic dermatitis patients produced LMIF when stimulated with ConA, as compared with 34 of 34 controls. This difference is highly significant.


Werner's syndrome: a model of premature aging? A 34 year-old woman with Werner's syndrome has been studied in the light of the current concept that this disorder is a model of premature aging. Endocrine function assays revealed an abnormal glucose tolerance and in vivo insulin insensitivity after prednisolone, and ovarian failure. Immune function assays revealed hypo-responsiveness in skin tests for delayed hypersensitivity, a poorly sustained IgG anti-body response after immunization with flagellin, and a low count of colony-forming T lymphocytes in blood. Cultured fibroblasts had a very limited capacity to replicate in vitro, in comparison with donors of similar age and, moreover, 85% of glucose-6-phosphate dehydrogenase in the patient's cultured fibroblasts was heat-stable at 60 degrees C compared with 100% for a healthy control. Cell receptors (for insulin) were examined by insulin binding to isolated fat-cells, with the finding that fat-cells were abnormally large for the patient's size, and their receptor density was low. The findings from the study point to a genetic defect in Werner's syndrome which, in its effect on particular tissues, may simulate features of aging, but the disease is not a true model of premature aging.


Stimulation of the short-circuit current (sodium transport) across the skin of the frog (Rana pipiens) by corticosteroids: structure-activity relationships. Aldosterone, at a concentration of 10(-8)mol/1, increases the short-circuit current (scc, a measure of active sodium transport) across the skin of the frog (Rana pipiens). The other natural amphibian corticosteroid hormone, corticosterone, is about 100 times less potent. The structure-activity relationships of a number of corticosteroids were studied with respect to this response. An 11 beta-hydroxyl group was essential, whereas unsaturation at the C-1 to C-2 positions abolished activity. A 17-hydroxyl group did not enhance the response. Fluorination at the 9 alpha-position increased the affinity of the steroid for the receptor. Synthetic corticosteroids which have a high ratio of glucocorticoid : mineralocorticoid action can increase the scc and one of these, dexamethasone, was even more potent than aldosterone. A methyl group at C-16 appeared to be an important constituent for this response but it had to be in the alpha-position. The effects of both aldosterone and dexamethasone were inhibited by spironolactone. The results are discussed in relation to the nature of the response and to corticosteroid receptors in the skin of amphibians.


Lens regeneration from cornea of larval Xenopus laevis in the presence of the lens. In Xenopus laevis tadpoles, wounding of the outer cornea failed to initiate lens regeneration. If both the outer and inner corneas were wounded or if the lens was dislocated, lens regeneration was initiated but failed to continue beyond stage III. However, lensectomy followed by re-implantation of the lens resulted in the regeneration of a fully differentiated lens in several cases, despite the presence of the re-implanted lens. Although some of the regenerates in these eyes were also arrested at stage III, those which attained full lens differentiation, i.e. stage V, developed normally and synthesized crystalline from the onset of stage IV as indicated by a positive immunofluorescence reaction. Histological examination of the dislocated and re-implanted lenses showed the majority of them to be normal in appearance. Cornea transplanted to the posterior chamber of the eye also regenerated a lens in the presence of the re-implanted lens. All these regenerates underwent lens fibre differentiation to give stage-V regenerates. These findings show that lens regeneration from the cornea can occur in the presence of lens. Results are discussed on the basis that contrary to earlier suggestions, an inhibitory lens factor does not exist in vivo, but rather that a factor for the initiation and maintenance of regeneration emanates from the eye cup and upon wounding of the inner cornea is able to reach the inner cell layer of the outer cornea and initiate lens regeneration.


Analysis of vestibulocollic reflexes by sinusoidal polarization of vestibular afferent fibers. 1. Canal vestibular-neck (vestibulocollic) reflexes have been studied in decerebrate cats by applying modulated polarizing current to individual ampullary nerves, usually the horizontal nerve. 2. Computer-generated stimuli sometimes consisted of sine or square waves at frequencies of 0.01--5 Hz. More often we used a compound wave form of nine superimposed sinusoids within an available frequency range of 0.009--6.11 Hz. The frequencies used were odd, relatively prime multiples of a base frequency selected to minimize distortion or interaction of responses. The response to each of the nine stimulating frequencies could be obtained in subsequent data analysis. 3. Responses to these stimuli were studied by recording the EMG of contralateral neck muscles and extracellular activity of second-order neurons. These neurons were identified by their monosynaptic responses to single-shock stimulation of ampullary nerves. 4. EMG was modulated sinusoidally. Below 0.1 Hz the response was variable, most likely due to differences in the preparations. In the frequency range of 0.1--0.4 Hz there was usually a phase lag, which decreased with incresing frequency and often reversed to a lead at 3 and 6 Hz. Gain decreased from the lowest frequencies, occasionally with an upturn at 3 or 6 Hz. 5. Second-order neuron firing was approximately in phase with the stimulus at the lowest frequencies. Phase advanced with increasing frequency to a lead of 30--50 degrees at 6 Hz. Gain generally increased with frequency. 6. By recording simultaneously from muscle and from second-order neurons, or by comparing the mean behavior of the two, it was possible to determine the central phase lag and gain of the vestibulocollic reflex. The lag was variable at low frequencies, had an average of 50 degrees at 0.18 Hz, and decreased to 20 degrees at 6 Hz. These results are comparable to those obtained by others using natural stimulation at frequencies of 1.0 Hz and below, and provide new information about the behavior of the central processer at higher frequencies. 7. The medial vestibulospinal tract (MVST), which contains the axons of crossed second-order vestibular neurons, was transected in six experiments. In agreement with previous workers there was no effect on phase at frequencies up to 0.4 Hz. There was also no selective effect of phase or gain at the higher frequencies. This shows that the disynaptic pathways in the MVST do not play any role that cannot be taken over by parallel pathways.