Protamine-precipitated estrogen receptor: a solid-phase ligand exchange assay.

Cytoplasmic estrogen receptor can exist either free (R) or bound to estradiol-17beta (RE). Both forms can be precipitated from cytosols by protamine sulfate. After protamine precipitation R binds 3-H-estradiol-17beta quantitatively at either 0 degrees or 30 degrees, while precipitated RE binds 3-H-estradiol-17beta only at 30 degrees by exchanging with previously bound hormone. Using these observations, we have developed a method for separate determination of both cytoplasmic R and RE. This method should also be applicable for assay of other steroid receptors, especially in cases where interfering components are present in the whole cytosol.


Dual infections of mice: visceral larva migrans and sublethal infection with Japanese encephalitis virus.

Experiments in 3 weeks old albino mice with Toxocara canis and sublethal infection with JE virus established a marked synergestic effect in dually infected mice. The results are discussed to indicate the possible role of visceral larva migrans in creating exploxive outbreaks of "acute encephalopathy syndrome" in individuals having simultaneous infection with a virus (es) which, alone, might produce only mild illness. The nature of the possible mechanisms involved yet remains to be understood.


[DNA-, RNA-, lipidsynthesis and the specific activity of the glucose-6-phosphate dehydrogenase and glucose-6-phosphatase in the different morphologic stages of Plasmodium vinckei].

DNA-, RNA-, and lipidsynthesis, glucose-6-phosphate-dehydrogenase, glucose-6-phosphatase and succinate-dehydrogenase were studied in the different morphologic stages of blood schizogony of Plasmodium vinckei. For the separation of these stages of the maturation cycle a discontinuous Ficoll-density gradient was developed. By this method the morphologic stages were separated and obtained in sufficient amounts. DNA-, RNA- and lipidsynthesis was not continuous in the intraerythrocytic cycle of the parasite. The glucose-6-phosphate dehydrogenase activity of the infected erythrocytes decreases whereas that of the glucose-6-phosphatase increases in the maturation cycle of P. vinckei.


[Morphologic, biochemical and functional properties of the mitochondria of the rabbit gastric mucosa].

Purified fractions of the rabbit gastric mucosa and liver mitochondria were isolated. Electrone microscopy and functional studies of mitochondria showed the most intact mitochondria of gastric mucosa to be localized in gradient fractions of  p=1.16-1.18, and those of the liver in fractions with p=1.19-1.20. The gastric mitochondria differed from the liver mitochondria by specific localization in oxyntic cells, abundance of crists, small matrix volume, presence of high respiratory control at lesser values of pH, high respiratory activity, great amount of cytochromes of electron transport chain in inner mitochondria membrane, two-fold excess of cytochroma a in relation to b and c, absence of b5 and by presence of great amount of phosphathydilaethanolamine and unsaturated fatty acids.


Primary signet ring cell carcinoma of bladder exemplifying vesical epithelial multipotentiality.

The eighth reported case of primary signet ring cell carcinoma of the urinary bladder is described clinically and pathologically. It is unusual because of complete replacement of the transitional epithelium by squamous and glandular metaplasia. The latter was particularly striking, demonstrating "normal" colonic mucosa, cystitis glandularis, well-differentiated adenocarcinoma, poorly differentiated adenocarcinoma, and the rare signet ring cell carcinoma variant. The possible origin of such changes is discussed.


Sarcoidosis and malakoplakia.

A case of malakoplakia in a patient with generalized sarcoidosis is reported. A discussion of the histologic and clinical characteristics is presented. This is the sixth case in the literature of concemitant malakoplakia and sarcoidosis. The suggestion is made that the two disorders may be related.


Depressed in vitro aggregation of platelets of chronic hemodialysis patients (CHDP): a role for cyclic AMP.

1) On log-log-coordiantes a direct correlation has bee shown to exist between plasma cyclic AMP and plasma Cr levels. 2) hemodialysis results in a significant reduction in the arterial plasma cyclic AMP levels, but a return of plasma cyclic AMP to pre-dialysis levels is seen within 30 mins post-dialysis. 3) the dialyzer clearance of cyclic AMP, both in vitro and vivo, is commensurate with its M.W. 4) In vitro platelet aggregation responses, to ADP, EPI, and COLL are not influenced by PRP cell counts between 150,000 and 300,000/mm3. 5) the BT of NC and CHDP are not significantly different, indicating that the in vivo hemostatic properties of the CHDP are otherwise intact. 6)the CHDP have PVPC significantly lower than the NC, a finding commensurate with the usual mold thrombocytopenia of renal failure. 7)the aggreation responses of the CHDP to COLL and to both Lo and Hi concentrations of ADP and EPI are significantly less than those of the NC. 8)A statistically significant inverse correlation between aggregation response and plasma cyclic AMP is observed.


Studies on the effects of hemodialysis on plasma lipoproteins.

Plasma Lps of the patients on maintenance hemodialysis and the patients with other specific renal diseases have been studied. The patients on hemodialysis frequently showed gross abnormality in their plasma Lps, which was differentiated from the abnormalities demonstrated in other renal diseases or clinical entities. An exception was type-III hyperlipoproteinemia; i.e. Lp electrophoretograms of the hemodialysis patients resembled those ultracentrifugal fractions had been made had VLDL of beta-migration in paper electrophoresis and another had VLDL or pre-beta-migration. During hemodialysis, intravascular lipolysis, accelerated by heparin infusion, affected all plasma Lps, producing an increase of alpha-Lps and cholestrol ester-rich-beta-Lp. The accelerated triglyceride hydrolysis under circumstances of high glucose availability may stimulate resynthesis of endogenous triglyceriderich Lps, which characterizes the plasma Lp abnormality in more than half of the hemodialysis patients. The abnormality may not be attribuate to the predisposing renal disease but due to an accumlation of the characteristic Lp during the course of maintenace hemodialysis. A possible cause of accelerated atherosclerosis in the hemodialysis patients may be the accumulation of remnants of plasma Lp catabolism and the stimulated synthesis of triglycerdie-rich plasma Lp.


Protective effect of modified silica gel fraction (MSGF) on the storage of canine liver for transplantation.

MSGF protects the function of canine ischemic (20mins) liver stored for 14 hrs. No significant liver protection, from irreversible damage, in dogs transplanted with ischemic livers, flushed with Ringer's lactate, Collins' solution, Sacks' solution or SGF before hypothermic storage was noted. Sacks' solution, although consistently better than Ringer's lactate and similiar to Collins' solution and SGF, was not half as good as MSGF.


[Comparison of the sensitivity of laboratory animals and tissue cultures to infection with Aujeszky's disease virus].

In mice and guinea-pigs high susceptibility was demonstrated following i. c. administration of the virus, approximately equalling to that of rabbits and tissue cultures. Also a relatively high susceptibility of guinea-pigs was demonstrated, with very distinct clinical symptoms of the disease, as compared with mice and rats after the other manners of infection. On the basis of the results obtained white mice were utilized for routine diagnostic of Aujeszky disease. After i. c. administration of positive, virus-containing material encephalitis develops with a rapid exitus occurring 12-24 hours earlier than in the rabbits. In brain tissue antigen was always demonstrated by immunofluorescence examination. Along with the biological experiment replicas of pig organs were examined by immunofluorescence method. Maximum of positive yellow-green fluorescence is found in the cytoplasma of epithelial tonsillar cells, sporadically in the cell nuclei. Epithelial cells are deformed according to the infection degree. The amount of antigen in the brain tissue is not so pronounced as in the tonsillar tissue, yet in animals with clinical pathological symptoms the antigen was always demonstrated.


Foot-and-mouth disease in British deer: transmission of virus to cattle, sheep and deer.

After exposure for two hours to cattle with foot-and-mouth disease, each of the five species of deer found in the British countryside became infected. Clinical disease was typical and severe in the roe and muntjac deer, with some animals dying, less severe in the sika deer and usually subclinical in the fallow and red deer. Each species transmitted disease to its own species and to cattle and sheep. The amounts of virus present in the blood, and in oesophageal/pharyngeal samples and excreted as an aerosol during the course of the infection in the deer were similar to those recorded for the sheep and cattle in the same experiment. The fallow and sika deer commonly carried virus in the pharynx beyond 28 days after exposure; some red deer also became carriers. In epidemics of foot-and-mouth disease in the UK, it is likely that deer would have such intimate contact with farm animals as occurred in this study. The natural behavior of free-living deer in the UK suggests that, although the five species are susceptible to foot-and-mouth disease, they are unlikely to be an important factor in the maintenance and transmission of the virus during an epidemic of foot-and-mouth disease in domestic livestock.


Newer knowledge in comparative virology--its contribution to human health research.

Like other comparative sciences, and despite its recent beginning comparative virology has already contributed useful applications and observations to human health research. Teachings derived from the study of Marek's disease found application in that of Burkitt's lymphoma, and may lead to a possible vaccine against the human disease. Equally useful information came from the study of canine distemper in the development of a chorio-allantoic membrane attenuated measles vaccine, and in our knowledge of subacute sclerosing panencephalitis (SSPE) of humans; from the study of reovirus-like agents of infant mice and neonatal calves in that of an acute nonbacterial gastro-enteritis of infants and young children; and from that of the cancer-producing viruses of chickens, cats, and dogs to a better understanding of some human neoplasias. Finally, Aleutian mink disease may be an excellent natural model for the study of the collagen diseases of man, and scrapie of sheep one for that of a human chronic degenerative disease of the central nervous system of humans such as Kuru. Comparative virology has proved quite productive in a relatively short period, and is unlikely to be neglected in the future.


Lipidosislike renal changes in rats treated with chlorphentermine or with tricyclic antidepressants.

Histological, histochemical and ultrastructural examinations were performed on renal tissues of rats after prolonged oral administration of the anorectic drug chlorphentermine or of the tricyclic antidepressants iprindole, imipramine and clomipramine. All drugs caused the formation of multilamellated cytoplasmic inclusions throughout the nephron and the collecting duct system, and in interstitial cells. The cytological alterations were most prominent in the glomerular podocytes, in the proximal convoluted tubules, and in the collecting duct system. In view of the histochemical properties (staining with Baker's acid hematein) and the ultrastructural appearance of the cytoplasmic inclusions the cellular alterations are interpreted as a renal manifestation of a generalized lipidosis induced by drugs of amphiphilic character.


Intracytoplasmic granule-lamella structures in visceral epithelial cells of human glomeruli.

A description is given of the rare occurrence of peculiar oblong structures having a maximal length of about 4.5 micron and a width of 0.5 micron, in the visceral epithelial cells of human glomeruli. These inclusions are marked by regular arrangement of parallel lamellae which are either in parts or over their whole surface associated with ribosome-like particles. Besides speculations on their origin and nature, some literature data come up for discussion.


Biological age and habitual physical activity in relation to physical fitness in 12- and 13-year-old schoolboys.

The purpose of this study was to investigate the relationship between biological age, habitual physical activity and anthropometrical and physiological characteristics in 12- and 13-year-old schoolboys (n = 70). At the beginning and the end of the school year 1971/2 biological age was determined by measuring skeletal age from left hand X-ray photographs. Habitual physical activity was determined by questionnaire interview and pedometers. All anthropometrical characteristics showed significant correlations (P less than 0.05) with skeletal age except for bicipital and tricipital skinfolds. Out of 9 physical fitness tests handgrip was the only test that showed a significant correlation (0.52) with skeletal age. Pedometer scores gave significant negative correlations (P less than 0.05) with anthropometrical characteristics except for tricipital skinfold. The fitness tests bent arm hang, 12 min run walk, sit and reach and W-170 showed significant correlations (P less than 0.05) with pedometer scores.


Size and distribution of SV 40 DNA Sequences covalently linked with the DNA of permissive mammalian cells.

CV-1 cells productively infected with SV 40 contain viral DNA which is covalently linked with the host cell DNA. These linear duplex viral-host DNA molecules are replicated during the infectious cycle. They can be selectively isolated and purified by two successive cycles of DNA-DNA hybridization and elution steps using first CV-1 cell and then SV 40-DNA immobilized on filters. In an attempt to clarify the nature of the host DNA sequences neighbouring the viral DNA it was found that reiterated host DNA must be within the range of 800 bases from the viral sequences. Reassociation kinetics and treatment of the reassociated viral-host DNA sequences with single strand-specific S1 nuclease have shown that unique host DNA sequences are always present in close neighbourhood of the viral DNA. Most of the SV 40 DNA sequences are probably intergrated as fragments of subgenomic length.


[Xenotransplantation of established tumor cells in congenital thymusless "nude" mice (author's transl)].

Successful xenotransplantation of 5 different established tumor cell-lines was performed in the congenital thymusless mouse mutant "nude". The tumors were one human carcinoma of the cervix (HeLa), one Burkitt's lymphoma as well as two Polyoma virus-induced tumors from rats and one spontaneous tumor from hamster. During an observation period of 21-28 days all cells formed rapidly growing tumors at the injection site. The critical cell dose varied in the different lines between 10-4 and 10-6 cells. Histological appearance of the neoplasias resembled that of the primary tumors. Two established lines from normal fibroblasts (3-T-3) and kidney (CV-1) failed to grow. Our results indicate that xenotransplantation in "nude" mice may serve as a simple in-vivo assay for testing the oncogenicity of tissue culture cells.


Respiratory activity of Ehrlich ascites tumour cell nuclei.

1. Intact Ehrlich ascites tumour cells exhibit a residual respiration which is insensitive to site-specific inhibitors of mitochrondrial electron transport. Treatment of the tumour-bearing mice with phenobarbital does not influence the rate of this inhibitor-resistant respiration. 2. Among the respiratory pigments analysed spectrophotometrically in the microsomal fraction prepared from ascites cells, only small amounts of flavoproteins (NADH-cytochrome b5 reductase and NADPH-cytochrome c reductase) were detectable. 3. Ascites-cell nuclei respire with NADH or NADPH, but not with succinate, as substrates and the respiration is unaffected by inhibitors of mitochondrial electron and energy transfer. These nuclei contain cytochrome b5, whereas cytochrome P-450 or mitochondrial-like cytochromes are lacking. 4. It is concluded that the NAD(P)H-dependent electron transport in nuclei is responsible for the inhibitor-insensitive O2 uptake of intact cells. Conversely, mixed function oxidation reactions of the endoplasmic reticulum have no role in this connection. Moreover, it is assumed that nuclear respiration is involved in the control of the cellular redox potential. 5. The relevance of the data obtained with respect to some assumptions concerning the biogenesis of the endoplasmic reticulum is discussed.


The fine structure of the cysticercoid of Hymenolepis diminuta. III. The scolex.

Transmission electron microscopy of the scolex of the 8-day-old Hymenolepis diminuta cysticercoid demonstrates its resemblance to the scolex of the adult. A syncytial tegument composed of external and internal layers is connected by cytoplasmic extensions. Fully developed microtriches are present. Furthermore, a basement membrane, muscle layers, and medullary region containing flame cells, nerve tissue, and other cell bodies are observed. Of particular interest is the presence of discrete sensory endings whose function is discussed.


Studies on the immunizing capacity of orally administered particulate antigens. I. The efficiency of killed Bordetella pertussis cells.

The single i.p. injection of 2.5 times 10-8 killed B. pertussis cells protected 23 out of a group of 24 NMRI mice (95.8%) against the subsequent intracerebral infection, whilst 13 out of 24 mice (54.2%) survived the intracerebral challenge with virulent B. pertussis cells after prior oral administration of 2.5 times 10-11 killed B. pertussis cells, as demonstrated by the mouse protection test. Similar treatment with non-specific substances, such as egg white and saline, did not result in any increase of resistance. Systemic anaphylactic hypersensitivity to bovine serum albumin could also be achieved, when either both the protein antigen and the B. pertussis vaccine were given by the oral route or when the B. pertussis vaccine was injected intraperitoneally into mice which had received the soluble protein antigen by the oral route. Such effects were not produced at all in the reverse situation, when the B. pertussis vaccine was orally administered in mice, which were given the soluble protein antigen by the intraperitoneal route. After oral inoculation of 6 times 10-11 killed B. pertussis cells neither splenomegaly nor blood lymphocytosis became detectable. It is still unknown, in which manner the orally administered B. pertussis vaccine effects protection against the intracerebral infection with virulent bacteria as well as susceptibility for systemic anaphylaxis. The data presented do not favor the view that those effects are due to the phenomenon of persorption.


Outbursting wedges of the colonies of Clostridium welchii containing chain forming mutants after ultra violet irradiation.

Cl. welchii NCTC 6785 was irradiated with UV light. The 40 minutes irradiated cells after 3-8 days ageing at room temperature (22-25 degrees C) and 48 hours initial incubation at 37 degrees C produced hairy outbursting wedges. These wedges gave rise to the colonies composed of chain forming mutants, which on transfer into the fluid medium grew into a pure chain forming culture.


[Pass-way of Epstein-Barr virus in the abortive infection of human lymphoid cells (author's transl)].

Biologically active, 3-H-thymidine-labeled Epstein-Barr virus has been purified by a method, specifically developed for these experiments, and used to infect the human lymphoid cell lines NC37 and Raji. At a late stage of this abortive infection (after 40 hr), 3-H-DNA has been recovered from the nuclei of the infected cells. This DNA has the density and size of free viral DNA. No evidence for integration was observed, in that less than 0,5 viral genome per cell had become covalently bound to cellular DNA. Simultaneously, the viral infection was studied by electron-microscopy.


Water structure in striated muscle by spin labelling technique.

The electron paramagnetic resonance (epr) spectra of a nitroxide-type free radical (4-hydroxy-2,2,6,6-tetramethyl-piperidinooxyl, tempol) of equilibrated in muscle water were measured. The results were analyzed in terms of the correlation time or microviscosity. The correlation time of spin probe was only four-five times higher in muscle water than in physiological solutions. The mobility gradually decreased with decreasing relative water content, a restricted mobility having been observed at low relative water content (i equals 0.3) only. The experimental results can be interpreted without assuming the major part of water phase in striated muscle to be ice-like or semicrystalline.


Enhanced vesicular transport of exogenous peroxidase across cerebral vessels, induced by serotonin.

Previous studies have revealed that the endothelial cells of cerebral vessels are linked by tight junctions preventing an intercellular passage of exogenous peroxidase. However, under normal conditions, vesicular transport of the tracer has been demonstrated in parts of cerebral vessels, especially in arterioles with a diameter of 30-100 mu. Solutions, containing 50-800 mug of buffered 5-hydroxytryptamine sulphate (serotonin), were perfused through the cerebral ventricles on mice after intravenous injection of horseradish peroxidase. Usually, the biogenic amine enhanced the vesicular transport of exogenous peroxidase. The serotonin-induced increased transport was observed in vessels on the surface of the brain as well as in vessels located in the parenchyma. No cell damage was observed. Increased transport was observed in arterioles, venules, and in capillaries. Therefore, it is not likely that the serotonin effect is a constriction of smooth muscle cells causing an opening of the tight junctions followed by an intercellular movement of tracer. The most reasonable assumption behind the mechanism is that serotonin affects the plasmamembrane of endothelial cells resulting in an enhanced production and transfer of cytoplasmic vesicles.


Clinical cytology of the liver.

A combined cytologic and histologic study of 149 needle-biopsy specimens of liver tissue was done. These specimens represented a wide range of normal and pathologic conditions. Malignancy was demonstrated in 27 cases--18 by both methods of study, one by histologic study alone, and eight by cytologic study alone. In the last group of eight, four were considered conclusive for malignancy and four were suspicious. These results confirm the findings of others who also report the advantages of combined cytologic and histologic study of needle-biopsy specimens for diagnosing malignancy. Similar results have been obtained with cytologic study of fine-needle aspirates. The commonly occurring cytologic findings in liver specimens are presented with a brief discussion of the specificity of the cytologic diagnosis of hepatocarcinoma.


Calcium metabolism.

It is evident that in the past decade much new information has been gathered regarding calcium metabolism at the physiological and extracellular level. In addition, new information is becoming available regarding intracellular mechanisms of calcium transport and mobilization. Finally, during the past decade the hormone calcitonin has been introduced as well as a hormone derived from vitamin D, namely 1,25-(OH)2D3, has been discovered and demonstrated to play a central role in the regulation of calcium metabolism. The exciting developments will undoubtedly foster the revelation of new information during the next decade which hopefully will bring about an elucidation of the molecular mechanisms of calcium metabolism.


Cytologic detection of early Paget's disease of breast with improved cellular collection method.

Improved cellular collection method and cytologic criteria for diagnosis of Paget's disease of the breast are presented. When indicated, the cytologic test is highly recommended for the early detection and pre-operative diagnosis of the minimal breast cancer10.


Renal tumours in children.

A ten-year series of renal tumours in children up to 14 years of age was collected from the files of the Finnish Cancer Register. After histological evaluation of the material, 74 cases were accepted as primary renal tumours. Fifty-eight of these were typical Wilms' tumours, three rhabdomyosarcomas, six foetal hamartomas and seven unclassified malignant tumours. Wilms' tumours were classified into three types on the basis of the histological differentiation. The total five year survival in the Wilms group was 50 per cent with no difference between patients over and under the age of one year. Of the subtypes of Wilms' tumours the sarcomatous type showed worse prognosis than average; only three out of 16 patients were alive after a five-year follow-up time. None of the patients with foetal hamartoma died of tumour, although two fatalities, connected with the surgery, were recorded. The value of histological classification of Wilms' tumours and the importance of the recognition of the foetal hamartoma is emphasized.


Carbon monoxide as a degradation product of cytochrome C and of ascorbic acid.

Cytochrome c has been incubated with 4 different reducing agents at 37 degrees C for 24 h at pH 7.0, and the spectral changes and the production of carbon monoxide have been followed. Only with hydrazine hydrate cytochrome c produced some carbon monoxide. Accidentally, carbon monoxide formation from ascorbic acid was found, amounting to about 0.1 mumol from 15 mumol of ascorbic acid in 24 h under the above conditions.


Degenerative changes in the human vestibular sensory epithelia.

A study of the vestibular end organs from humans of different ages is presented. The inner ears were exposed by microdissection, and the vestibular sensory regions were either sectioned and studied with light or electron microscopy, or prepared and studied with the surface specimen technique. A change, which can be related to aging, is the accumulation of lipofuscin inclusions in sensory and supporting cells, especially pronounced in the type I sensory cell. Changes of the hair bundles, such as disarrangement of cilia, increased fragility of cilia and formation of giant cilia, have also been observed in aged individuals. In three cases there was a history of vestibular disturbance of vertigo. All three cases had shown caloric hypo-reactivity. In two cases, one with a history of herpes zoster oticus and another with a brain stem glioma, no morphological changes which could be attributed to the diseases, were found. The third case showed degeneration of macula utriculi and the lateral and superior cristae, possibly as a result of vascular disturbance.


Rate limiting factors in sympathetic neurotransmitter secretion.

Isolated superfused field stimulated preparations of guinea-pig vas deferens, in which the neural stores of noradrenaline (NA) had been labelled by preincubation with tritium-marked (-)-NA, were used to study the factors regulating the amount of NA secreted from the nerves, per applied shock. The results indicate that "Stimulation secretion coupling" in this tissue is subject to 2 different kinds of facilitation, one independent and one dependent on nerve stimulation frequency. Kinetic analysis of the calcium dependence of transmitter secretion, after removal of alpha-adrenoceptor mediated negative feedback control, suggests that there is a definite upper limit to the amount of transmitter which can be secreted, per pulse, from each "secretary area" of the nerves. The low Q(10) value of this apparent V(maz) suggests that the rate limiting factor is non-enzymatic in nature. It is proposed that the ultimately rate limiting factor in NA secretion may rather be the number of vesicles in each potential "secretary area" which are in a suitable position within the nerve for active participation in the secretion of transmitter.


Effects on the ventral spinocerebellar tract neurones from Deiters' nucleus and the medial longitudinal fascicle in the cat.

Effects from the vestibulospinal tract (VST) and from fibres descending in the medial longitudinal fascicle (MLF) on the cells of origin of the ventral spinocerebellar tract (VSCT) have been studied with intracellular recording. Out of 110 VSCT neurones, the VST evoked monosynaptic EPSPs in 27, di- or polysynaptic EPSPs in 56 and disynaptic IPSPs in 26. In 93 tested VSCT cells, MLF stimulation evoked monosynaptic EPSPs in 26, monosynaptic IPSPs in 2, di- or polysynaptic EPSPs in 25 and disynaptic IPSPs in 21. Convergence of monosynaptic EPSPs from VST and MLF was found in a small proportion of cells whereas the two descending pathways evoked reciprocal effects in another small group of neurones. Convergence of monosynaptic EPSPs from VST or MLF and from group I afferents was also modest. In 9 VSCT neurones there was convergence of monosynaptic excitation and disynaptic inhibition from the vestibulospinal tract and the same pattern from MLF was recorded in 9 neurones. The results are discussed in view of the hypothesis that VSCT neurones carry information on the interneuronal ttransmission in the spinal cord.


Mitochondrial respiration in the ventricular myocardium and in the white and deep red myotomal muscles of juvenile tuna fish (thunnus thynnus L.).

The respiratory activity of mitochondria isolated from the outer and inner layers of the ventricular myocardium and from the white and deep red myotomal muscles of juvenile Thunnus thynnus has been compared. The highest values for the succinate oxidase and succinate cytochrome c reductase activities have been found in the mitochondria of the outer myocardial layer, followed by mitochondria of the deep red muscle, the inner myocardial layer and the white muscle in that order. Differences in mitochondrial NADH-cytochrome c reductase activity run parallel, in a lower order of magnitude, to the differences in the oxidation of succinate. This finding is discussed in relation to the different metabolic attitudes of the muscle tissues towards anaerobic glycolysis. The outer myocardial layer of the juvenile tuna ventricle has been shown to have a higher metabolic activity than the inner layer, in contrast to the situation in adult ventricular myocardium.


The action of dibutyryl adenosine-3':5'-cyclic monophosphoric acid and theophylline on the isolated cat parotid gland.

In the isolated cat parotid gland intraarterially applied dibutyryl cyclic AMP (db-cAMP) (1.0 mM) produced a slow, but often maintained salivary flow. db-cAMP was also able to potentiate secretion evoked by supramaximal doses of intraarterially applied acetylcholine. Similar secretory effects were obtained also after intraarterial application of theophylline (1.0 mM). The secretory responses due to db-cAMP or theophylline were unaccompanied by measurable acinar membrane potential changes and stayed unchanged after cutting the parasympathetic innervation of the gland and after blocking both cholinergic and beta-adrenergic receptors with atropine (10-minus 7 M), and with D-(minus)-N-isopropyl-p-nitrophenol-ethanolamine (INPEA) (10-minus 5 M), respectively. The possibility of the existence of an acinar adenylate cyclase system functionally linked to the beta-adrenergic membrane receptor is discussed.


Adult hypophosphatasia.

A case of adult hypophosphatasia under treatment with a high orthophosphate (P1) intake is described. The patient is a 53-year-old woman. Her symptoms have progressed for seven years, and it has been necessary to perform osteosynthesis of both crura. The diagnosis rests upon a characteristic clinical picture, low serum alkaline phosphatase activity, high urinary excretion of phosphoethanolamine, and an invariably elevated concentration of inorganic pyrophosphate (PP1) in plasma accompanied by a very high excretion of this compound in the urine. An improved technique allowed specific determinations of microquantities of PP1 in biologic materials. The concentrations of PP1 in the plasma and urine remained unchanged when the patient's intake of phosphorus was increased to 1.98 g/day. The PP1/P1 ratio in the urine was 10-20 before treatment. During treatment P1 excretion increased. PP1 excretion did not change, and the ratio decreased to around 7. The renal tubular transport of PP1 probably was saturated, and therefore PP1, which was circulating in abnormally high concentrations in the patient's fluids, could not be removed by loading with P1. Four months of treatment did not benefit the patient.


Mammalian liver alcohol dehydrogenases.

Literature on the properties of liver alcohol dehydrogenase (ADH) from man, horse and rat is reviewed and discussed under two major headings: 1) physical and chemical properties of ADH and 2) structure-function relationship in isoenzymes. Under the first heading are discussed: molecular weight, subunit composition catalytic sites per molecule, sulfhydryl groups, end groups, amino acid composition, role of Zn++ in the structure and function, coenzyme specificity and binding, conformational changes, substrate specificity, catalytic mechanism and recent results from x-ray crystallography of horse liver ADH. The physicochemical properties of ADH from man, horse and rat are for the most part similar. All three enzymes have identical molecular weights, similar amino acid compositions, consist of two subunits, and are all metalloenzymes containing Zn++: horse and human ADH contain one coenzyme binding site per subunit; no results are available for the rat ADH. ADH catalyses interconversion of a large variety of saturated and unsaturated aliphatic and aromatic alcohols and the corresponding aldehydes and ketones utilizing NAD(H). The physiological role of ADH is uncertain. ADH readily combines with reduced coenzymes to form binary complexes with low dissociation constants (10-7 to 10-8M); in the ternary complexes with coenzymes and substrate-competitive inhibitors, these constants are even lower. In the presence of suitable inhibitors, the enzymes can be titrated by coenzymes employing fluorometric and spectrophotometric procedures. The rate of the overall reaction catalyzed by ADH is determined by the dissociation rates of coenzymes, the slowest steps in the reaction sequence. Under the second heading are discussed: liver ADH isoenzymes of horse, man, rat, rhesus monkey and other species, and the significance of steroid activity which accounts for the distinct substrate specificity of some isoenzymes. ADH from horse liver is a heterogeneous enzyme consisting of subunits of distinct substrate specificity and primary structure. The difference in the amino acid sequence between subunit E (active with classical ADH substrates, but not with steroids) and subunit S (active also with steroids) amounts to six amino acids out of 374. Human ADH is also heterogeneous, and at least five genes code for polypeptides which, by dimerization, form different isoenzymes. Experimental evidence suggests that rat ADH is a single unique protein which, like horse liver ADH, SS, is active with steroids. The physiological significance of steroid activity of ADHs is unknown. (Four tables with comparative data and one figure are presented).


The effects of aliphatic alcohols on the biophysical and biochemical correlates of membrane function.

The simplicity of the structure of aliphatic alcohols suggests that their interaction with receptors in the classical sense is unlikely. The actions of alcohols may involve a relatively nonspecific disruption of cell membranes, possibly physically dissolving into neuronal membranes especially, resulting in the malfunction of normal physiological processes. Studies of alcohol-membrane interactions have employed the use of artificial and nonneural membranes, invertebrate neurons for electrophysiological measurements and brain tissue for studying ion fluxes and enzymatic activities. For the most part these studies have been inclusive because high concentrations of alcohols were needed to elicit any effect. Also, it is difficult to extrapolate the data to in vivo mammalian systems, especially relative to the clinical signs of depression of the central nervous system.


Interactions of ethanol with cyclic AMP.

Ethanol and other alcohols stimulate adenylate cyclase activity in various tissues and potentiate its stimulation by some hormones. This effect, however, usually requires a high alcohol concentration. In some cases, an unknown substance, different from cyclic AMP, was formed from ATP in the presence of an alcohol and mimicked stimulation of adenylate cyclase. Ethanol inhibits phosphodiesterase activity in some tissues. In the brain, only the low affinity enzyme of pons-medulla region is inhibited. ATP levels and ATPase activities are affected by ethanol treatment and this can lead to secondary changes of the cyclic AMP levels. Cyclic AMP levels in the brain and liver are decreased by acute ethanol administration while levels in other organs are unchanged. High doses of ethanol inhibit the postdecapitation-induced rise of cyclic AMP level in the brain while low ethanol doses potentiate the postdecapitation rise of cyclic AMP in the lower brain stem. Chronic ethanol administration increases basal adenylate cyclase activity and cyclic AMP levels, and decreases stimulation of adenylate cyclase by norepinephrine in the brain. In contrast, the stimulation of cyclic AMP formation by norepinephrine and other biogenic amines is increased in the brain of ethanol-withdrawn animals. Chronic administration of ethanol affects also cyclic AMP levels and cyclic AMP formation in some peripheral organs. Cyclic AMP might be involved in ethanol-induced fatty liver, since it activates hepatic lipase and might also participate in the fatty acid oxidation.


Rate-limiting steps in ethanol metabolism and approaches to changing these rates biochemically.

Ethanol is oxidized to acetate primarily by a system involving liver alcohol and aldehyde dehydrogenases coupled with reoxidation of NADH by the mitochondria. All of these steps are at least partially rate-limiting in ethanol metabolism, with alcohol dehydrogenase and oxidative phosphorylation probably slower than the others. More research is required to assess the quantitative roles of various steps. Many agents are ineffective in changing the rate of metabolism of ethanol, but fructose and dinitrophenol may increase the rate by up to 1.5-fold in vivo. The failure of single agents to increase the rate substantially may indicate that when one step is accelerated, another step becomes rate-limited. Therefore, combinations of agents that affect several steps simultaneously may be required for acceleration. Effective experimental methods for inhibiting alcohol dehydrogenase in vivo are available.


The effects of feeding various carbohydrates on the development of hypercholesterolemia and atherosclerosis.

It is possible to establish atherosclerosis in rabbits by feeding semi-synthetic diets that are high in carbohydrate and saturated fat and devoid of cholesterol. Addition of saturated fat to laboratory chow does not render the chow atherogenic. When rabbits were fed diets which differ only in the carbohydrate component, starch was found to be more atherogenic than sucrose which, in turn, was more atherogenic than glucose. All the diets were hypercholesteremic and hypertriglyceridemic. In another series of experiments diets containing fructose or sucrose were more atherogenic than diets containing glucose, lactose or sorbitol. Baboons were feed semi-synthetic diets containing fructose, sucrose, starch or glucose (but no cholesterol) for one year. Serum cholesterol levels were 155-165 mg/dl in all test groups. The normal baboon cholesterol level is 115 mg/dl. Serum triglycerides were elevated from the normal level of 73 mg/dl to about 110 mg/dl in the groups fed starch and glucose and to about 125 mg/dl in the groups fed fructose and sucrose. Liver and lung cholesterol ester levels were also raised. The test groups all showed aortic sudanophilia. The most severe sudanophilia was observed in the fructose group (11.2% of surface area) and the least in the glucose group (6.2% of surface area). The biliary cholesterol specific activities (after administration of (3-H)-melvalonic acid) were the same in all groups, but biliary bile acid specific activity was higher in the control baboons than in test animals. These data, plus the higher primary/secondary bile acid ratio observed in the test animals, suggest that reduced bile acid synthesis may be one cause of the hypercholesteremia observed in animals fed the semi-synthetic diets.


Piribedil and apomorphine: pre- and postsynaptic effects on dopamine synthesis and neuronal activity.

Piribedil and apomorphine can cause a complete but temporary inhibition in firing of the DA-containing neurons. The cells recover to approximately 30 to 40% of the original firing rate, and with subsequent administration of the drug become more and more resistant to further inhibition. At this point they are also resistant to inhibition by other direct- or indirect-acting DA agonists that are normally able to inhibit the firing of DA cells. This effect may be due to an interaction of the DA agonists with the postsynaptic DA receptors, but apomorphine at least is able to inhibit the firing of DA cells directly when iontophoresed onto the DA cell body (Aghajanian and Bunney, 1973). These drugs can block the increase in DA synthesis observed in the absence of impulse flow, indicating a presynaptic site of acttion. Taken together, these results suggest that in interpreting the effects of drugs interacting with the DA systems several points of interaction should be considered.


The efficiency of protective hoods used by sandblasters to reduce silica dust exposure.

Several types of respiratory protective hoods used by sandblasters were investigated in two steel fabrication yards. MSA Gravimetric Dust Samplers were used to collect respirable dust samples outside and inside hoods during sandblasting. Colorimetric and x-ray diffraction techniques were applied to the samples for free-silica determination. The majority of the sandblasters, who wore various types of air-supplied hoods, were exposed to an average level of silica dust several times higher than the TLV. Sandblasters wearing non-air-supplied hoods were at the greatest risk. Modern well maintained and properly worn air-supplied hoods offered fair protection during sandblasting periods, but the concentration of suspended respirable dust in ambient air during non-blasting intervals exceeded the TLV by several times.


A retrospective study of clinical, physiologic and immunologic changes in workers exposed to toluene diisocyanate.

A retrospective study was made of workers in a toluene disocyanate plant using an immunologic test procedure developed at the NIOSH laboratories. Case histories of 32 workers in seven response groupings are presented. Sensitization was found to correlate with the frequency and severity of significant exposures to TDI. Immunologic changes producing tolerance to TDI exposure also resulted in negative response to the antigen challenge tests. Some individuals exposed to TDI may have protective antibodies but still experience bronchoconstriction.


A technique for dynamic calibration of a continuous toluene diisocyanate monitor.

A method was developed for generation of atmospheric concentrations of toluene dissocyanate at 0.005 to 0.08 parts per million. This paper describes an analytical methods for the calibration of a continuous 701 Monitor using a diffusion cell to generate constant concentrations of TDI.


Policy and procedural guidelines for the health and safety of workers in virus laboratories.

Through the use of a (a) a questionnaire, designed to elicit background information, (b) a serological survey, designed to obtain a picture of virus dissemination, and (c) a library review, designed to gain insight into the area of virus laboratory problems, the state of hazard in animal virus laboratories at Yale was evaluated. On the basis of this evaluation, a series of recommended guidelines for protecting the health and safety of workers in those laboratories was formulated.


The genesis of cell types in the adenohypophysis of the human fetus as observed with immunocytochemistry.

Hypophyses of 21 human fetuses, ranging in gestational age from 6 to 23 weeks, were studied by immunocytochemical and histological staining to ascertain (1) the time of origin of specific cell types and (2) the development of parenchymal cell zonation in the pars distalis. No hormones were identified at six weeks. Probable corticotrophin-containing cells appeared at seven weeks. Somatotrophs were observed first at 10.5 weeks; correlation with other reports indicates that they appear at eight to nine weeks. Melanotrophs were detected at 14 weeks; the cells containing melanotrophin were far fewer than corticotrophs. The youngest fetus to possess gonadotrophs was 10.5 weeks old. In all specimens gonadotrophs (LH-cells) stained well with immunocytochemical procedures but poorly with histological methods. Thyrotrophs first occurred at 13 weeks. Zonal distribution of cell types in the pars distalis was evident almost from the time of their appearance. Somatotrophs were most numerous laterally and immediately anterior to the residual cleft. At 10.5 weeks corticotrophs were confined chiefly to the borders of vascularized connective tissue (trabeculae) and to the lateral peripheral region of the pars distalis. Thyrotrophs appeared chiefly in the anteromedian zone, particularly in its superior portion, but were found laterally also. In the older specimens, gonadotrophs generally occurred throughout the pars distalis but were less numerous near the trabeculae and in the anterolateral region. There was good correlation between the time of appearance of various cell types and published data on secretory capacity of the gland.


Morphological effects of a large single dose of cycloheximide on the intestinal epithelium of the rat.

Adult male rats received 15 mg/kg cycloheximide and the subsequent morphological effects at three and six hours after injection were evaluated using histometry, light and electron microscopy, histological demonstration of terminal web and acid phosphatase, and radioautography with tritiated thymidine. Rapid atrophy of the villi took place, progressing from the villus tip by premature exfoliation of epithelial cells. The crypts also diminished by random exfoliation of many crypt cells and by partial or complete disintegration. Mitosis and epithelial cell migration were absent. By six hours, the area occupied by the villi and the crypts per unit length of histological section was decreased by about 70-90% in most of the small intestine but only by about 40-60% in the duodenum and the terminal ileum. In the upper half of the villi, the epithelium was strongly positive for acid phosphatase and contained large numbers of round bodies resembling primary lysosomes. In the lower half, the microvillous border and terminal web were found to be disrupted. Animals receiving only 5 mg/kg cycloheximide also showed the atrophy of villi and crypts, and the round bodies resembling lysosomes. Evidence from several sources has indicated that protein synthesis in normal villus epithelial cells subsides toward the villus tip and becomes minimal at exfoliation. At exfoliation, proteins responsible for epithelial cohesion probably fail because they are no longer replenished. Cycloheximide appears to accelerate this process.


Cytomegalovirus studies of autopsy tissue.  I. Virus isolation.

From January through September 1973, 55 virus isolates were recovered from lung and kidney specimens from 44 (8.8%) of 502 unselected autopsy cases. Cytomegalovirus (CMV) was isolated 42 times in 34 cases (36 from lung, four from kidney, and one each from pleural and bronchial tissues). Virus isolation was approximately six times more sensitive than histologic detection of CMV infections. Major causes of death included solid malignant tumors, leukemia, lymphoma, and renal allograft rejection; 13 patients had a variety of other diseases, predominantly cardiopulmonary. CMV was recovered from more males than females. The mean age of the CMV-positive group did not differ significantly from that of the CMV-negative group. CMV-positive cases were not preselected on the basis of specimen processing time. Serologic results indicate that recovery of CMV from an autopsy case was seven times more likely when the complement-fixing antibody titer was 1:16 or more.


Cytomegalovirus studies of autopsy tissue. II. Incidence of inclusion bodies and related pathologic data.

Cytomegaloviruses (CMV) were recovered from lung tissue in 34 (6.8%) of 502 unselected autopsy cases. Inclusion bodies were detected in the lung in nine of these cases (26%) and in organs other than the lung in three others. Overall, the incidence of inclusion bodies in this series of 502 cases was 2.4%. Our data strongly indicate that virus isolation is more sensitive than histopathologic study in establishing the presence of CMV infection. However, CMV was not recovered from one kidney and one liver in which inclusion bodies were present, although the virus was isolated from lung. Four of five cases of renal allograft rejection were positive for both CMV and inclusion bodies. The incidence of CMV recovery and inclusion body detection in leukemia and lymphoma cases was more than twice that in cases with other diseases. CMV inclusion bodies with or without associated inflammation were found, in descending order of frequency, in the lung, kidney, liver, pancreas, adrenal gland, esophagus, prostate, testes, thyroid gland, parathyroid gland, stomach, small intestine, large intestine, and heart.


Ultrastructure of the skeletal muscles in acromegaly--before and after hypophysectomy.

Electron microscopic examination of the skeletal muscles in a patient with acromegaly and marked elevation of the serum growth hormone reveals altered mitochondria (pleomorphism, elongation, matrical pallor, and cristae abnormalities), glycogen granules infiltration, inclusion bodies, and vesicular dilatations.  Nine months after surgical removal of the pituitary tumor, the serum growth hormone levels were markedly diminished.  A repeat examination of the skeletal muscle shows that the previous ultrastructural changes in the muscles are related to the growth hormone levels.


Anaerobic infections of the female genital tract.

Anaerobic bacterial organisms are a frequent cause of female genital tract infections. There has been a lack of appreciation of the significant role anaerobes play in obstetric and gynecologic infections. Utilization of newer appropriate anaerobic culture techniques has shown the importance of these organisms as pathogens in serious infections of the genital tract. Many species of anaerobic bacteria appear to be part of the normal microflora of the lower genital tract in female subjects. Similar organisms are frequently isolated from pelvic infections. Bacteroides, anaerobic cocci, and Clostridia are the most commonly isolated anaerobes associated with clinical infections. The clinician must recognize the presence of anaerobic infections, utilize proper anaerobic culture methods, and institute appropriate antibiotic and/or surgical therapy.


Comparison of antibiotic therapy in presumptive bacterial conjunctivitis.

One hundred twenty patients who met criteria for presumptive bacterial infections of the conjunctiva were closely recorded for two weeks in a double-blind study that compared the effectiveness of gentamicin with a combination of neomycin and polymyxin B sulfates. The neomycin and polymyxin B combination demonstrated statistical superiority as measured by patient improvement and failure to respond to therapy. However, difficulties including chance distribution of bacteria and variability of organism resistance may have detracted from statistical results.


Cytochemical localization of lysosomal enzyme activity in normal and ischemic dog myocardium.

The effect of ischemia on the integrity of myocardial lysosomes was observed 3 1/2 and 24 hours after the production of infarcts in 20 anesthetized closed-chest dogs by electrically induced thrombosis of the left anterior descending coronary artery. Biopsies from normal, marginal and infarcted areas were fixed and incubated to localize the lysosomal enzymes acid phosphatase and aryl sulphatase. Reaction product in normal cells was localized in small circular or oblong profiles between bundles of myofilaments and adjacent to mitochondria. In addition, curvilinear, membrane-bound profiles containing reaction product were found in close apposition to transverse tubules and near the free margins of the myocardial cells. Thus the distribution of elements of the sarcoplasmic reticulum. Additional reaction product was also seen in residual bodies, on myelin figures, and in the few conventional appearing spherical lysosomes. Little or no acid phosphatase or aryl sulphatase reaction product was seen in the sarcoplasmic reticulum of infarcted myocardium. The degree of cellular degeneration correlated with disappearance of enzyme activity from the sarcoplasmic reticulum and included disruption of membranes and loss of mitochondrial matrix and erosion of I but not A bands. Marginal areas showed variable amounts of cellular degeneration. Separation of myofilament bundles and loss of glycogen correlated with the localized disappearance of acid phosphatase and aryl sulphatase activity in marginal tissue. Disruption of mitochondrial and erosion of I bands correlated with extensive loss of these enzymes. The data suggest that degeneration of myocardial cells following ischemic injury is associated with release of endogenous lysosomal enzymes from the sarcoplasmic reticulum.


Mixed endocrine pancreatic tumors producing several peptide hormones.

Twenty-four endocrine pancreatic tumors were examined immunohistochemically for insulin, glucagon, gastrin and ACTH. In seven of these tumors, more than one peptide-hormone-containing cell type was observed. These seven tumors were also examined with conventional staining methods for the presence of A1, A2, and B cells. The results showed that these staining methods do not always distinguish between the different hormone-producing cell types of endocrine pancreatic tumors. In spite of the fact that several types of hormone-secreting cells were found in the tumors, the case histories described symptoms characteristic of hypersecretion of only one of the hormones. The hormone of the predominating cell type could not always explain the clinical symptoms. Our results indicate the endocrine pancreatic tumors often are multihormonal. Therefore, it would seem advisable to screen serum from all insuloma patients for a variety of peptide hormones.


Experimental parainfluenza-type-1-virus-induced encephalopathy in the adult mouse. An ultrastructural study of early lesions.

The adult mouse inoculated intracerebrally with 6/94 strain of parainfluenza type 1 virus developed selective degenerative lesions in cerebral white matter. Ultrastrucrally, the infiltration of mononuclear cells, mostly lymphoid cells, apparently preceded the alterations of white matter parenchyma. The prominent feature of the white matter lesion was a lytic degeneration of both axon and myelin that seemed to be triggered by the mononuclear cell infiltration. Nucleocapsids of paramyxovirus were found only in ependymal cells and the very early stages of the infection. It is suggested that the mechanism of the white matter degeneration might be that of a virus-induced cell-mediated immune response directed at both the axon and myelin.


Phylogenetic significance of the skin of New World monkeys (order primates, infraorder Platyrrhini).

The combined properties of a given cutaneous system, like other characters classically employed by systematic zoologists, are useful criteria in the assessment of primate taxonomy and phylogeny. From the synthesis of all available data, it is also concluded that (1) the results define a baseline regarding the normal histology and histochemistry of the skin of most genera and many species of New World monkeys; (2) intrageneric and intraspecific subtleties in cutaneous variation exist in primate integument; (3) single and multiple cutaneous traits contribute to the characterization and accurate identification of most levels of taxa within the primate hierarchy; (4) some traits, however, negate recent taxonomic practices, e.g., the familial position of Callimico; (5) basic cutaneous patterns confirm currently accepted concepts of taxonomy and phylogeny; and (6) the various cutaneous signatures of extant platyrrhines record a history of adaptive radiation in isolation, and suggest that the designation of at least two distinct families is warranted.


Age changes in the pubic symphysis of Macaca mulatta.

Age changes in the pubic symphyses of 142 Cayo Santiago rhesus monkeys (known age, sex and maternal genealogy) are described. Symphyseal development is sexually dimorphic. Males generate a ridge and furrow system which is gradually replaced by a solid ankylosis at the mid-sagittal plane. Female development parallels that of the male until puberty. With pregnancy and delivery, relaxation and reaggregation of pelvic ligaments binding the  symphysis destroy the symphyseal face. Continued bearing of offspring inhibits mid-sagittal ankylosis. Limited estimates of skeletal age can be made by using symphyseal development as an indicator of senescence.


Resocialization of schizophrenic patients.

An increasing number of chronic schizophrenic veterans is being discharged through various community placement programs. Because of years of separation from the social changes that have occurred in the society they once knew, these veterans need to be reoriented to community living. This study describes the responses of four chronic schizophrenic veterans who participated in a program of intensive reorientation. After exposure to this program, the veterans' ability to show empathy for one another was more eventful than their accomplishment of specific skills. Follow-up evaluations indicated that the veterans had gained social interest and competence and demonstrated less pathology.


Impaired renal response to parathyroid hormone in potassium depletion.

In potassium depletion, a possible alteration of the proximal tubular response to parathyroid hormone (PTH) was evaluated in rat kidney. 1) There were impairments of both phosphaturic and urinary cyclic AMP responses to PTH. The site of the impairment was further investigated by studying the PTH-dependent cycle AMP system in renal cortex. 2) There was a lesser increase of cyclic AMP concentration by PTH in potassium-depleted slices, indicating the lesser urinary cyclic AMP was due to the specific impairment of PTH-dependent cyclic AMP in the kidney. 3). The activation of adenylate cyclase by PTH was impaired , but phosphodiesterase activity was not affected by potassium depletion, indicating the impairment of cyclic AMP generation  was due to inhibition of adenylate cyclase. 4) The  phosphaturic response to dibutyryl cyclic AMP infusion was also significantly less in the potassium-depleted animals, indicating the step subsquent to the cyclic AMP generation  is also impaired. All above results indicate that, in potassium depletion, the renal response to PTH is impaired, and the impairment is both within the step of cyclic AMP generation and after the cyclic AMP generation.


Uptake of adenosine by dispersed chich embryonic cardiac cells.

Adenosine is involved in the regulation of coronary blood flow, but its mechanism of action is not clear. The present investigation is an attempt to understand the mechanism(s) of uptake of adenosine in dispersed chick embryonic cardiac cells and its relationship to the adenosine hypothesis. Adenosine is readily taken up by these cardiac cells, and a small fraction is incorporated into adenine nucleotides, whereas a major fraction is deaminated to inosine. The mechanism of uptake is different in 12- to 15-day-old chick embryos compared to 16- to 22-day-old embryos. The younger embryo heart cells show the incorporation of adenosine into adenine mononucleotides of the incubation medium as well as all the adenine nucleotides of the cells, whereas the older embryo heart cells show incorporation of adenosine only into the adenine nucleotides of the cells. The isolated cells used in the present study do not leak any significant amounts of adenosine kinase and/or nucleotides, and free adenosine was not found in the cells, even with extracellular concentrations as high as 1 mM. The absence of free adenosine in isolated dispersed cells reflects the activities of adenosine kinase and adenosine deaminase and is compatible with the adenosine hypothesis for the regulation of coronary blood flow.


Control of hepatic glycogen metabolism in the rhesus monkey: effect of glucose, insulin, and glucagon administration.

The effects of intravenous glucose, insulin and glucagon admininistration on the hepatic glycogen synthase and glycogen phosphorylase systems were assessed in the anesthetized rhesus monkey. Results were correlated with measurements of hepatic cyclic AMP (cAMP) concentrations and plasma glucose, insulin, and glucagon concentrations. Both glucose  and insulin administration promoted significant inactivation of phosphorylase by 1 min, which was followed by more gradual activation of synthase. Neither glucose nor insulin caused significant changes in hepatic cAMP. Marked hyperglucagonemia resulting from insulin-induced hypoglycemia did not cause increases IN in hepatic cAMP, suggesting that the elevated insulin levels possibly inhibited glucagon action on the hepatic adenylate cyclase-cAMP system. Glucagon administration caused large increases in hepatic cAMP and activation of phosphorylase within 1 min, followed by more gradual inactivation of synthase when it had been previously activated by glucose. Concomitant glucose infusion, with resulting increased plasma insulin concentrations, markedly diminished the duration of hepatic cAMP elevations following glucagon adminstration, again suggesting an insulin inhibition of glucagon action on the hepatic adenylate-cAMP system.


Angiotensin and the hemodynamics of chronic salt deprivation.

Salt deprivation has been shown to cause fluid volume contraction and marked renin release; it is not clear whether angiotensin-induced vasoconstriction adds to low volume in compromising circulatory function or whether there are additional facets to the salt-deprived state. Mature Wistar rats were fed a low-salt diet for 1 mo and then, under pentobarbital anesthesia, compared to normals. Arterial pressure (is congruent to 125 mmHg), cardiac output (is congruent to 200 ml/min per kg), and total peripheral resistance were nearly identical in both groups. The influence of angiotensin was estimated by injecting converting enzyme inhibitor (SQ 20881, 1 mg/kg), and then observing the immediate hemodynamic response. Salt-deprived rats responded with a large (-47 mmHg) fall in pressure and total peripheral resistance indicating that, although total peripheral resistance was normal in salt deprivation, an increased fraction (30% vs. 11%) of the resistance was supported by angiotensin. Cardiac output decreased (-8%) in contrast to the increase that would be expected during marked arterial dilation; elevated angiotensin levels may have caused a moderate, beneficial decrease in venous compliance. These results suggest that circulatory function is adequately maintained during salt deprivation by a combination of normal total peripheral resistance and decreased venous compliance.


Aggregation and release in thrombocytes of the duck.

Avian thromboyctes are aggregated by a number of substances that cause platelet aggregation, and evidence suggests that this response is related to the release of serotonin (5-hydroxytryptamine, 5-HT) from intracellular granules. In this study duck thrombocytes released 5-HT during collagen-induced aggregation, but thrombocytes incubated with 14C-labeled adenine did not release radioactive adenine nucleotides. These results indicate the existence of a metabolic pool of adenine nucleotides that is separate from released constituents of the cell. No unlabeled adenine compounds were detected in the supernatants of aggregated thrombocytes indicating either the rapid alteration of released nucleotides or the absence of a specific release pool of adenine nucleotides. Finally there is no release of the intracellular enzyme markers, lactate dehydrogenase, beta-glucuronidase, and acid phosphatase, during collagen-induced aggregation. These findings suggest that avian thrombocytes exhibit a specific release reaction and that serotonin acts as the functional counterpart of ADP in platelet aggregation.


A phylogenetic study of the role of cyclic AMP in lipid synthesis in vertebrates.

The effect of cyclic AMP on the incorporation of acetate-2-14C into sterols and fatty acid in vitro in slices of liver and intestine was examined in various representatives of the vertebrate group. In no instance was an effect on lipid synthesis noted in intestine. Cyclic AMP exerted no significant effects on hepatic lipogenesis in lower vertebrates, including the nurse shark, catfish, toad, or iguana. However, the nucleotide strongly inhibited the incorporation of acetate-2-14C into fatty acid by the chicken liver. Similar inhibition of fatty acid synthesis was also noted in rat liver, but in this mammalian species hepatic sterol synthesis was also strikingly suppressed by cyclic AMP. Interruption of the enterohepatic circuit in the rat, while enhancing rates of sterol synthesis in both liver and intestine, neither enhanced nor diminished hepatic susceptibility to suppressed sterologenesis by cyclic AMP, nor did it confer on the intestine any newfound capacity for cyclic AMP-regulated lipid synthesis.


Comparison of two five-year follow-up studies: 1948 to 1952 and 1967 to 1972.

Results of a 5-year follow-up of 100 randomly selected patients committed to a community-oriented mental hospital in 1947 are compared with those of a 5-year follow-up of 100 randomly selected patients admitted to a community-based mental health center in 1967. The data show that both programs were successful in kepping patients with historis of long-standing mental illness in the community, even thought the 1947 group did not receive any modern psychotropic medication. One uoexpected finding of the comparison is the suggestion that these drugs might not be indispensable; in fact, they might actually prolong the social dependency of some discharged patients.


Brief transference-focused therapy of hospitalized psychiatric patients.

A therapeutic approach referred to as brief transference-focused therapy for hospitalized psychiatric patients is discussed with its three key constituents being early selective intervention, the nurturing of positive transference, and the active participation of the patient in determining posthospital treatment. Clinical examples are presented in which these constituents are illustrated. Gains and limitations of this treatment are discussed.


Roentgenographic findings in fucosidosis type 2.

The roentgen findings are described in 2 siblings with fucosidosis Type 2. They have mild dysostosis multiplex with predominant involvement of the spine, pelvis, and femoral capital epiphyses. The roentgen descriptions of the previously reported cases are reviewed. Based on the descriptive data currently available, there are no consistent differences which would permit the distinction of fucosidosis Type 1 from Type 2 on roentgen grounds.


Light and electron microscopic study of dysplastic rosette-like structures occurring in the disorganized mature retina.

Histopathologic examination of six, adult human eyes revealed "rosette-like" structures in the retina which appear to have developed after maturation of the retina. These structures resemble dysplastic rosettes which are generally interpreted as a sign of maldevelopment of the retina (retinal dysplasia). The underlying lesions in the eyes of these patients were ocular ischemia, sickle-cell retinopathy, diabetic retinopathy, central retinal vein occlusion, and trauma. It is suggested that a distinction should be made between these degenerative-regressive changes and dysplastic rosettes which represent an abortive attempt of regeneration by germinal cells.


Studies on the liver of Xenopus laevis. I. The ultrastructure of the parenchymal cell.

The liver of Xenopus laevis was examined with electron microscopy. Its structure was found to be markedly different from that of mammals, particularly regarding the morphology of the hepatocytes to be classified as typical. It was established that the main function of such a cell is the storage of glycogen, and further that it possesses only scant organelles and other inclusions. Since this type of cell was found most frequently in the liver of untreated animals, it was designated as normal cell. The fact appears noteworthy that in the normal liver of Xenopus laevis an abundance of cell types occur which are otherwise found to be proliferated under experimental conditions, e.g. cells with pronouncedly augmented RER, enlarged Golgi complexes, increased lipid inclusions etc. This high number of divergent hepatocytes and the fact that all intermediate stages between the individual extremes are present and not to be accounted for by the position of the cell within the liver was interpreted as being the expression of a cyclic passage of the various stages of activity. It is of special interest that augmented degradation of glycogen in the liver cell takes place only during vitellogenesis. Acute and chronic hunger, as well as adaptation to cold, hardly affect the morphology of the normal cell, especially as far as the glycogen is concerned. The possible causes for this are discussed.


Fine structure of the interrenal cell in the quail and the pigeon.

The ultrastructural characteristics of the interrenal cell were investigated in the quail and the pigeon after fixation by intravascular abdominal perfusion. There is no significant fine structural difference between cells belonging to subcapsular and central regions of the gland. The interrenal cell in both species possesses nuclear bodies, polymorphic mitochondria with tubulo-vesicular cristae and tubular crystalline inclusions, considerable amounts of endoplasmic reticulum, ergastoplasm, a well developed Golgi apparatus, coated vesicles, microtubules, filaments, cilia, ribosomes, a profusion of liposomes, dense bodies with varied inner structure, pinocytic invaginations of cell membrane and intercellular attachment devices. The pigeon adrenorcortical cell also possesses intranuclear lipidlike inclusions and fibrous bundle (this being never recorded in adrenocortical cell), annulate lamellae, and a variety of cytosomes, probably lipofucsin in nature. The significance and cytophysiological role of various organelles and inclusions have been discussed in the light of earlier data obtained on avian adrenocortical cells.


Acute effects of ACTH on dissociated adrenocortical cells: quantitative changes in mitochondria and lipid droplets.

To study the role of certain organelles in steroidogenesis, dissociated rat adrenocortical cells were incubated for two hours with ACTH at a concentration that induces a high level of steroid production. Sections of ACTH treated and untreated cells were photographed in the electron microscope, and morphometric analysis was undertaken to assess possible ACTH-induced changes in total cell volume, volume density and numerical denisty of lipid droplets and mitochondria. There was no change in total cell volume. Lipid droplet volume density and numerical density decreased. Mitochondrial volume density did not change, but numerical density increased. The decrease in lipid droplet volume density indicates a rapid depletion of cholesterol for steroid production. This depletion is almost entirely due to the disappearance of lipid droplets, rather than to an overall diminution in their size, as shown by the decrease in lipid droplet numerical density. The mitochondrial data suggest that the adrenocortical cell has an adedquate mitochondrial apparatus to respond to acute ACTH stimulation with increased steroid output without an increase inmitochondrial volume.


Inhalation anesthetics and cytochrome P-450-dependent reactions in rat liver microsomes.

The activities of liver microsomal enzymes were studied in preparations from unanesthetized rats and rats anesthetized for one hour with nitrous oxide, diethyl ether, halothane or chloroform. Most of the enzymes studied were cytochrome P-450-dependent oxygenases that hydroxylate endogenous substrates. The other microsomal enzymes, assayed for comparison, included the cytochrome P-450-dependent aminopyrine demethylase, glucose-6-phosphatase, a dehydrogenase, and NADPH-cytochrome P-450 reductase. No anesthetic was associated with a significant change in activity of any enzyme studied. In rats pretreated with phenobarbital no anesthetic except chloroform changed enzymic activity. All hydroxylations were inhibited markedly by chloroform, as were a microsomal dehydrogenation, hydrolysis of glucose-6-phosphate, and NADPH-cytochrome P-450 reductase activity. Administration of alpha-tocopherol did not prevent the inhibition associated with chloroform in phenobarbital-induced animals. It is concluded that cytochrome P-450-dependent hydroxylations involved in metabolic processes normally proceeding in the endoplasmic reticulum of the liver are not permanently affected by the anesthetics used in this study. The inhibitory effect of chloroform after pretreatment with phenobarbital is unspecific and affects a large number of different microsomal enzymes. Evidence that mechanisms other than lipid peroxidation may be responsible for the toxic effects of chloroform in the liver is presented.


Virus-like particles in buffy coat cells of normal goats and goats infected with progressive pneumonia virus.

By electron microscopy, virus-like particles (VLP) were seen in neutrophils and lymphocytes from buffy coats prepared from 5 goats inoculated with progressive pneumonia virus (PPV) and 3 noninoculated goats. The VLP were 80 to 120 nm in diameter, limited by a unit membrane, and resembled PPV, visna virus, and other members of the oncornavirus family. Some VLP seemed to have electron-dense nucleoids and external spikes. In neutrophils, VLP were observed budding into vacuoles; rarely, intravacuolar clusters were seen. In lymphocytes, VLP were seen in vacuoles. Free VLP and budding of VLP from external cell surfaces were not seen. In vitro incubation of buffy coat cells with mitogens did not affect the frequency of VLP. Although the VLP are similar to PPV, the exact nature of the particles and their relationship to PPV is not clearly understood.


Comparison of the characteristics of avian reoviruses isolated from the digestive and respiratory tract, with viruses isolated from the synovia.

Two-week-old gnotobiotic chicks were inoculated in the foot pad with viruses isolated from synovia and synovial membrane-WVU 1464-29H, WVU 1675, WVU 2937, WVU 2986, and WVU 71-212; from digestive tract-reoviruses 24, 25, and 59; or from respiratory tract-reovirus Fahey-Crawley (FC). All viruses induced swelling of the foot pad and inflammatory changes of synovial membrane. Serum from virus-infected chicks had a common agar gel precipitin (AGP) line. On the basis of the plaque-reduction test in primary chicken kidney (PCK) cells, the viruses were classified into 4 major serotypes. All viruses produced cytopathic effects (CPE) in primary chicken tissue cultures. Other than reovirus FC and WVU 1464-29H, all viruses produced CPE in the Vero cell line.


An unusual case of feline leukemia and an associated syncytium-forming virus.

A 3-year-old female Siamese cat was admitted to a local animal hospital with a history of recent extreme lethargy and anorexia. A hemorrhagic tumor was removed from an area of oral buccal skin and diagnosed histopathologically as lymphosarcoma. Rapid physical deterioration occurred, and the cat became moribund 2 weeks after surgical operation. Necropsy revealed at least 200 spherical hemorrhagic neoplastic nodules attached to the omentum, mesentery, and peritoneum. Examination of histopathologic sections confirmed the striking characteristics of an extremely vascular and highly invasive malignant lymphoma, which was designated feline tumor No. 01 (FeT-01). There was no evidence of peripheral blood leukemia. Electron microscopic examination of tumor tissue revealed numerous viral particles having characteristics common to both feline leukemia virus (FeLV) and feline syncytium-forming virus (FeSFV). Primary cells and cultures propagated from tumor tissue were found to be negative or weakly positive for group-specific (gs) antigen by radioimmunoassay but strongly positive when assayed by indirect immunofluorescence. Co-cultivation of cells from tumor tissue, with normal prescreened feline embryo cells, revealed the presence of numerous FeSFV-like viral particles in the absence of C-type virus. A FeSFV was isolated from these passaged cells, with characteristics similar to FeSFV isolates previously described in the literature. The apparent presence of FeSFV in lymphosarcomatous tissue and the apparent absence of FeLV C-type particles in passaged cells indicate the need to make a more intensive study of the FeSFV group of viruses and the possible etiologic relationship to feline malignancies.


Comparative pathogenicity of avian encephalomyelitis viruses in chicken embryos.

Multiplications of wild, various embryo-adapting and completely embryo-adapted avian encephalomyelitis (AE) viruses in chicken embryos were compared by the fluorescent-antibody technique (FAT). With a wild AE virus, viral antigens were randomly seen in the central nervous system (CNS), appearing least often in the cerebellum. Other organs seldom became test positive, except for heart and kidney. Even with 4 chicken brain-passaged viruses in the process of embryo adaptation, there was little augmentation of antigens except in the alimentary tract. However, the 2 midpassage viruses showed a peculiar localization of antigens in the white matter of the lumbosacral cord, together with the appearance of test-positive spinal ganglion cells. With 2 strains of embryo-adapted AE virus, the antigens appeared first in the spinal ganglion cells and secondly in the lumbosacral cord and then spread to the cerebrum. Subsequently, clinical signs of AE were evident. This peculiar invasion order was a prominent feature.


Cross-reactions of normal bovine serums to foot-and-mouth disease virus in plaque-reduction neutralization and radial immunodiffusion.

Serums from 150 cattle with no known exposure to foot-and-mouth disease (FMD) virus were tested by both the plaque-reduction neutralization (PRN) technique and the radial immunodiffusion (RID) technique to evaluate the significance and the extent of cross-reactions in these tests. Serums from 30 cattle from each of 5 locations were tested against representative viruses of each of the 7 types of FMD virus. High levels of cross-reactions with both the RID and PRN techniques were found in serums of specific groups. Higher levels of cross-reactions were noted for Asia, SAT I, SAT II, and SAT III than for A, O, or C viruses with the PRN technique, and higher levels for SAT II and SAT III with the RID technique. The reactions for most serums appeared to be quite specific; a given serum was often reactive with only 1 or 2 viruses.


Pulmonary tuberculosis and coexisting carcinoma: a 10-year experience and review of the literature.

Of 7,986 patients admitted to Mount Wilson State Hospital for Pulmonary Diseases between 1960 and 1970, 72 were proven to have coexisting pulmonary tuberculosis and bronchogenic carcinoma. The patients usually were in the older age group, and usually smoked. There was a high predilection for the tumor to occur in the upper lobes. Active tuberculosis was present in 50 per cent of the patients and tumor and tuberculosis was present in the same area 80 per cent of the time. Cell diagnosis was possible in 60 per cent of the patients without thoracotomy. Diagnosis was usually made late in the course of the disease and therapeutic results were poor. Only 13 patients were operable and only four are presently alive. Earlier recognition is vital to adequate treatment. A plan for earlier recognition based on a high degree of suspicion is presented.


Postpartum hemorrhage into a large nonfunctioning islet cell tumor of the pancreas.

A case of postpartum hemorrhage into a nonfunctioning islet cell tumor of the pancreas is presented. The manifestations and surgical management of this tumor are discussed. The incidence and pathological significance of such a tumor are examined.


Current and future concepts of lung cancer.

We discuss here some of the last decade's diagnostic and therapeutic advances in the treatment of lung cancer, as well as current and future research objectives. Roentgenographs from selected patients illustrate the natural history of lung cancer. We present perspectives concerning selection from the growing diagnostic armamentarium, with comments upon early detection and localization of "occult" cancers with the help of flexible bronchoscopy. Operative approaches have changed over the past 4 decades; we review how and why they evolved, including perspectives concerning mediastinoscopy. There is a presentation on a radiotherapeutic research approach to oat-cell cancers and the current status of immunotherapy. Such issues as animal models available for lung cancer research emerge in the general discussion, and it becomes clear that lung cancer merits a truly interdisciplinary approach in order to bring meaningful advances to the patient's bedside.


Polymyxin B reactions, IgE antibody, and T-cell deficiency. Immunochemical studies in a patient after bone marrow transplantation.

A patient with aplastic anemia was immunosuppressed with cyclophosphamide and transplanted with allogenic bone marrow. While lacking demonstrable T-cell activity posttransplantation, he developed a generalized macular erythematous eruption and fever, clinically attributed to intranasal polymyxin B. A specific IgE antibody, demonstrated by direct skin testing, Prausnitz-Kustner passive transfer, and indirect passive hemagglutination was temporally related to the reaction. Discontinuation of the drug led to prompt defervescence and resolution of the drug eruption.


Effectiveness of neomycin and polymyxin ointments: prevention of Staphylococcus Aureus keratitis in rabbits.

Combinations of neomycin sulfate and polymyxin B sulfate are commonly used in ophthalmic ointments for the treatment or the prevention of bacterial keratoconjunctivitis. In this study we evaluated the effectiveness of various ointments containing these two antibiotics, alone and in combination, in preventing Staphylococcus aureus keratitis in rabbits. Rabbit eyes were infected by intracorneal inoculation, treated topically with ointment and graded by gross observation 24 hours after inoculation. Treatment with ointments containing neomycin alone offered significant protection against these corneal infections. The polymyxin B ointments, as well as the vehicle controls, were ineffective in preventing S aureus infections in the rabbit eyes. However, by far, the most effective ointment formulations tested were the combination ointments and specifically those containing 1.75-3.50 mg neomycin and 3,000-6,000 units polymycin B per gram of ointment.


Effects of anesthesia on intermediary metabolism.

Major inhalational anesthetics cause inhibition in the electron transport chain in the region of Complex I resulting in decreased oxygen utilization, inhibition of metabolism of NAD-linked substrates, but not of succinate, inhibition of mitochondrial calcium uptake, and depression of synaptic transmission because of postulated changes in ACh sensitivity or GABA inhibition. Many cellular metabolic effects in CNS and other tissues are secondary to the above. Many metabolic changes noted with anesthetics occur subsequent to activation of the sympathetic nervous system either directly by the anesthetic or by surgical stimulation in the presence of light anesthesia. Many important studies remain to be done.


Neuroregulators and sleep mechanisms.

Information which has emerged thus far relates to the overall transmitter mechanisms of sleep. The data, while conflicting, point to the involvement of many neuroregulators at numerous integrative levels of the process. However the long term question still remain: what triggers and maintain sleep, what stops sleep, what occurs to the body and brain during sleep--in essence, why sleep? These questions are now problems for behavioral neurochemists, whereas in a previous era, they were problems for philosophers. Unfortunately, our answers to date, while in another idiom, have hardly been more complete or satisfying. To answer these questions, it will be necessary to understand, in detail, the manner in which neurobiochemical processes relate to the functional physiology of sleep. Although existing studies have given invaluable insight into the neurochemical anatomy of sleep, we have only recently acquired the technical and biochemical expertise necessary to investigate sleep as it occurs normally. Future research must focus on the dynamic changes associated with the regulatory mechanisms of neurotransmitters. Many questions can be asked. With sleep transitions, what changes occur in transmitter content, synthesis, or release? Are there changes in metabolic pathways, reflecting a shift from intra- to interneuronal metabolism? What changes occur in pre- and postsynaptic neurotransmitter receptors to affect sensitivity? What constraints do genetic (245) and environmental (246) factors impose upon these mechanisms? Knowledge of such parameters will allow us to construct more complete models of the neuroregulatory basis of sleep and waking. However, as we acquire this knowledge, we must avoid the temptation of assuming causation when the evidence merely shows correlation. Neuroregulation are involved in the control of number different behaviors; and, at present, we have few, if any, methods of establishing causative links between a specific neuroregulator and a specific behavioral state. Yet, even without an understanding of what "causes" sleep, we may be able to develop pharmacological agents which permits discrete alteration of sleep mechanisms in a more physiological and specific manner. This potential for manipulation of sleep is of obvious importance in illnesses such as insomnia, narcolepsy, and sleep apnea (247, 248). In addition, it may be valuable in the treatment of such conditions as psychosis and depression, where sleep disturbances are an important component of the illness. For example, delirium tremens might be best understood as a psychotic episode which is the result of an aspect of sleep emerging into wakefulness. The range and breadth of both the basic questions and the potential application of sleep research portend an exciting future for this field.


Effect of calcium and magnesium ions on the susceptibility of Pseudomonas species to tetracycline, gentamicin polymyxin B, and carbenicillin.

The effect of calcium and magnesium on the susceptibility of 13 species of Pseudomonas to tetracycline, gentamicin, polymyxin B, and carbenicillin was measured. The majority of the minimum inhibitory concentrations (MICs) of these antibiotics was increased if these cations were added to the test media. The increases in MICs caused by calcium or magnesium were similar, but the combination of both ions generally caused a greater change than either alone. Although the MIC of polymyxin B was most affected by calcium and magnesium, its interpretive susceptibilities (i.e., whether susceptible or resistant) were least changed. Susceptibility tests on Pseudomonas species probably should be done with Muller-Hinton broth supplemented with physiological concentrations of calcium and magnesium to better approximate the in vivo activity of these antibiotics. When the susceptibility tests were performed with Mueller-Hinton agar, the MICs were slightly less than those obtained with Mueller-Hinton broth supplemented with both cations but greater than those obtained with Mueller-Hinton broth supplemented with individual cations.


Inhibition of the growth of hemadsorption 2 virus by three acyl derivatives of amino acids.

Three acyl derivatives of amino acids, dicarbobenzoxy-l-lysine sodium, carbobenzoxy-l-aspartic acid-beta-benzyl ester potassium, and N-3-phenylpropionyl-S-benzyl-l-cysteine potassium inhibit the growth of parainfluenza 1 (hemadsorption 2) virus. The growth of simian virus 40, vaccinia, poliomyelitis type 1, Semliki Forest, Eastern equine encephalitis, and Western equine encephalitis viruses was not affected by these compounds. Four other acyl derivatives of amino acids did not inhibit the growth of any of the viruses tested.


Growth curves of anaerobic bacteria in solid media.

Simple pour plate and spectrophotometric techniques for the evaluation of growth curves of several anaerobic bacteria on solid media are described. Three basic patterns of anaerobic growth were observed. The curves obtained were very reproducible when studied on separate occasions. The curves obtained by spectrophotometric measurement were comparable to those obtained by the pour plate method, especially when a large bacterial inoculum was used. Limitations in the interpretation of the results are discussed. The methods and principles reported could provide the basis for the determination of bacterial growth on solid media using other organisms and different experimental conditions.


Effects of lead on the lipid composition of Micrococcus luteus cells.

Micrococcus luteus cells cultivated in medium containing lead salts exhibited a sequence of changes in the quantity of total cellular lipids with essentially no changes from normal cellular yields. The lipid composition of cells cultivated one to four times was moderately decreased (phase I) whereas that of cells cultivated five to six times was reduced by as much as 50% (phase II). Cells cultivated more than six times in lead-containing media had progressively greater quantities of lipid (phase III) approaching that found in control cells. These cells with reestablished lipid contents showed no further effects from more prolonged exposure to lead salts. Chromatographic studies of total lipids of cells of each lipid phase revealed relatively complete lipid compositions. These results indicated that lead is apparently affecting a common biochemical parameter in the biosynthesis of lipids of lipid phase II cells. Changes in the relative quantities of individual components were observed in both the nonpolar and polar lipids in each lipid phase. The most notable changes were the decrease in aliphatic hydrocarbons with concomitant increases in the diglycerides and components identified as a complex family of ketones. Microscopy examinations of control and lead-treated cells revealed electron dense inclusion bodies in membrane fragments in only lead-treated cells.


Comparative study of four microporous filters for concentrating viruses from drinking water.

Four microporous virus-absorbent filter media for recovering low levels of virus from 380 liters of drinking water were compared. In addition two of the filter media were compared with 1,900 liters of drinking water. The filter media evaluated were MF nitrocellulose membranes (293 mm), AA Cox M-780 epoxy-fiberglass-asbestos disks (267 mm), K-27 yarn-wound fiberglass cartridges + AA Cox M-780 disks (127 mm), and Balston epoxy-fiberglass tubes (24.5 by 63.5 mm). The filters were used to concentrate seeded poliovirus from 380 liters of finished drinking water. Sodium thiosulfate was added to the drinking water to neutralize chlorine, and hydrochloric acid was added to adjust the pH to 3.5. Virus was eluted from the filters with glycine-NaOH buffer at pH 11.5. In terms of virus recovery efficiency, the filter media ranked Balston greater than Cox 267-mm greater than MF 293-mm  congruent to  K-27 + Cox 127-mm, but differences were slight. The Balston filters and holders were also superior to the other systems in terms of size, weight, cost, and handling factors. Experiments with 2- and 8-mum porosity Balston filters showed no statistically significant difference in virus recovery. Virus was readily detected by the Balston and the MF 293-mm systems at input levels of 12 to 22 PFU/1,900 liters. Preliminary experiments indicated that an elution pH lower than 11.5 may be satisfactory.


Gardner-Diamond syndrome with multiple glomus tumors.

The case of a patient with two unusual dermatologic entities, multiple glomus tumors and the painful purpura of Gardner-Diamond syndrome, is reported. The diagnosis of multiple glomus tumors was confirmed by biopsy, and the Gardner-Diamond syndrome was confirmed by reproduction of the painful purpura with the intradermal injection of the patient's sonicated erythrocytes.


Calcium balance in children treated with diphosphonates.

Serial mineral balances have been obtained in 3 children undergoing therapy with EHDP (ethane-1-hydroxy-1, 1-diphosphonate) for diseases involving ectopic calcification. Although clinical outcome was not uniformly satisfactory, all cases showed an overall reduction in calcium balance. This was due to increased faecal excretion of calcium and was most marked after a long duration of therapy. Although these results conflict with reported experience in adults, they are in agreement with published observations of the effects of EHDP on calcium absorption in experimental animals.


Psoriatic therapeutics and glucose-6-phosphate dehydrogenase.

The inhibitory effects of various agents on the enzyme glucose-6-phosphate dehydrogenase have been studied in vitro. Stress is laid on the calculation of kinetic parameters such as true K-I values. The most active inhibitor was methotrexate, closely followed by cGMP. The increase in inhibitory activity after incubation of methotrexate with liver slices is discussed.


Wound infection during the Yom Kippur war: observations concerning antibiotic prophylaxis and therapy.

Eighty-eight episodes of wound associated infection were identified among 624 consecutively admitted battlefield casualties. Ninety-one per cent of infections occurred during the administration of antibiotic therapy or prophylaxis and 65% were associated with the use of multiple antibacterial agents. Gram negative bacillary and mixed microbial infection predominated and were found to increase in relative incidence after the second day of hospitalization. Appropriate therapy, based on disc sensitivity testing, was administered in only 33% of infectious episodes. The practice of antibiotic wound prophylaxis may contribute to the incidence and nature of infection in battlefield wounds. Problems unique to the handling of battlefield wounded are discussed in comparing the present data with those of other war associated and civilian studies.


Flavoxate, a potent phosphodiesterase inhibitor.

The c-AMP phosphodiesterase inhibiting properties of flavoxate and of its main metabolite i.e. 3-methylflavone-8-carboxylic acid (MFCA), were assayed in vitro and compared to those of theophylline. Flavoxate and MFCA are competitive phosphodiesterase inhibitors, and are 21 and respectively 5 times more potent than theophylline. The smooth muscle relaxing activity of flavoxate possibly relies on this enzymatic mechanism.


High synovial fluid white blood cell counts in pseudogout; Possible confusion with septic arthritis.

During a 12-month period, we have treated five patients with acute inflammatory arthritis and synovial fluid leukocyte counts of 65,000 to 100,00/cu mm with 93% to 100% polymorphonuclear cells, calcium pyrophosphate dihydrate crystals in the synovial fluid, and negative cultures. Four of these five were origingally treated for septic joints. We would like to emphasize this relatively uncommon, but important manifestation of pseudogout.


Changes in phosphatase activity associated with cell wall defects in Chlamydomonas reinhardi.

Experiments were performed to isolate mutants lacking alkaline phosphatase in Chlamydomonas reinhardi. Mutants with null enzyme activity were obtained. A cytological study of these mutants however revealed cell wall defects, suggesting that the loss of phosphatase activity in these strains is not due to the inactivation of the corresponding phosphatase structural gene but rather to the leakage of this enzyme as a consequence of the cell wall abnormality. Incidentally, this finding provides the basis of a convenient method for selecting easily cell wall mutants of Chlamydomonas.


On the structure of the peptidoglycan of cell walls from Myxobacter AL-1 (myxobacterales).

Basically the peptidoglycan of Myxobater AL-1 consists of alternating beta-1,4-linked N-acetylglucosamic-N-acetylmuramic acid chains. After splitting the aminosugar backbone with a specific algal enzyme three subunits arise: a monomer, a dimer and a timer. Investigation of the monomer with specific enzymes and comparison of the degradation products to standards derived from other bacterial peptidoglycans suggest the following structure of the monomer peptide: L-alanyl-D-glutamic-L-meso-diaminopimelic-D-alanine. A D-alanyl-D-meso-diaminopimelic acid bond is the bridgebond between the peptides of the subunits.


The effect of soluble antigens from polyoma tumor and liver cells on stimulation of lymph nodes measured by incorporation of 14C-leucine.

The effect of solube antigens from polyoma tumor cells, liver antigens and PHA on lymph node cells from tumor bearers and on normal lymph node cells in CBA mice was studied. The stimulation index was calculated on the basis of incorporation of 14C-leucine in short-term cultures. The stimulation index was lower in lymphocytes derived from tumor bearers than those from normal donors. The blastoid responses to polyoma-associated antigens and PHA were similar, in contrast to liver-associated antigens. It was concluded that stimulation of liver antigens may be connected with different chemical structure, mainly of carbohydrate components.