Studies of in vitro asbestos-cell interaction.

Using amosite and chrysotile, asbestos cytotoxicity is shown to be a function of time and is abolished by filtration of the culture medium containing asbestos fibers through a 0.2-micrometer filter. There is evidence that cytotoxicity is related to the phagocytic property of cells since non-phagocytic fibroblasts survive under conditions lethal to P388D1 cells. Time lapse studies show that apparently normal mitosis occurs in the presence of intracellular asbestos, but the presence of fibers in sufficient quantity results in cytotoxicity. Effects on human (WI-38) fibroblasts are also reported.


Inhibition of aflatoxin B1-induced cytotoxicity and binding to DNA in cultured rat liver cells by naturally occurring flavones.

For naturally occurring flavones, quercetin, fisetin, nobiletin, and tangeritin, protect cultured rat liver epithelial-like cells against aflatoxin B1-induced cytotoxicity and inhibit the binding of [3H] aflatoxin B1 to cellular DNA. The methoxy-substituted flavones, nobiletin and tangeritin, show greater protection against cytotoxicity than do the hydroxy-substituted compounds, quercetin and fisetin.


Correlation of calculated electronic parameters of fifteen aniline derivatives with their mutagenic potencies.

Electronic parameters for a series of amino-, chloro-, and nitro-substituted anilines relative to their potential for activation to hydroxylamines, aryl-nitrenium ions, and ring epoxides, and to their potential deactivation to phenols were calculated using semi-empirical molecular orbital methods. The relative mutagenic activities of aminoanilines could be explained by parameters reflecting potential for N-hydroxylation and stability of the arylnitrenium ions. Both chloro and nitro groups deactivate the amine group to N-hydroxylation and the ring to epoxidation, and no active products from cytochrome P-450 would be predicted. This result is consistent with lack of mutagenic activity observed for chloro derivatives, but does not account for activity of the nitro derivatives, which is presumed to be due to transformation of the nitro group itself to an active mutagenic species by other enzyme systems.


Toxicity of aerosols of sodium reaction products.

Sodium is used as the heat transfer medium in several new energy technologies such as liquid-metal fast-breeder reactors and solar-thermal collection systems. Because sodium burns in air and reacts violently with water, the potential exists for an airborne release of sodium combustion products and subsequent human exposure. To help evaluate the potential short-term hazard from an accidental sodium fire, male juvenile or adult Wistar rats were exposed to sodium aerosols for 2 hours to determine the dose at which 50 percent of the animals were affected (ED50) for each age group. The estimated ED50 of 510 microgram/l for adults was not significantly different from the estimated ED50 of 489 microgram/l for juveniles. The incidence of acute laryngitis, attributed to exposure, was three times higher for juvenile rats than for adults, and the degree of severity of this lesion was significantly (P less than 0.05) higher for juveniles.


Matching-to-sample and oddity-from-sample in goldfish.

Acquisition of three-alternative simultaneous matching-to-sample and oddity-from-sample was investigated. Five goldfish were trained on matching and five on oddity for a minimum of 70 days. Subsequently, six of the fish were trained for 70 days on the other task. Acquisition was similar for oddity and matching. Correct responding started at about chance level and slowly increased to about 75%, with some animals performing at levels of over 85%. Acquisition of oddity following matching and matching following oddity began below chance. Maximal level of performance on second-task oddity was comparable to that on first-task matching. By contrast, the maximal levels of performance when matching was the second task were not as high as that of the same subjects at the end of first-task oddity. All fish exhibited strong color preferences during matching acquisition but not during oddity acquisition. The data demonstrated that goldfish can acquire a discrimination in which the stimulus associated with reinforcement depends on the identity of a second stimulus.


Control by stimulus features during fading.

Sixteen children were given four successive circle-size discrimination problems with luminance as the fading stimulus. Children who were first presented with a difficult size discrimination failed to acquire this discrimination. Those who first received an easy discrimination learned the difficult discrimination. At the end of each 10-trial block, two probe stimuli were presented to monitor any shift in control from luminance to size. One probe was the same size as the positive stimulus but of different luminance; the other was the same luminance but of different size. If, in the course of fading, size and luminance both controlled responding, fading was successful. If luminance alone controlled responding until the end of fading, the size discrimination was not established. Dual control, and thus successful fading, resulted when the target stimuli were very discriminable, or when the target stimuli were subtly different provided that previous fading series had first established less subtle discriminations.


Developmental studies of the lethal gene Bld in the mouse. I. Post-implantation development of the lethal homozygote.

In matings of Bld/+ x Bld/+ mice a characteristic type of abnormal embryo is found on days 6 and 7 after impregnation which dies at 8 days and accounts for about 25% of all living embryos. These embryos are regarded as the fethal Bld/Bld homozygotes. Before 6 days the embryos appear slightly retarded. Entodermal cells invade the yolk sac and the trophectoderm does not fuse to the uterine decidua. Late on day 6 the yolk sac is filled with a cap of unorganized cells of entodermal origin, surrounded by both a thick membrane of non-living material, corresponding to Reichert's membrane, and external to this a continuous layer of trophectoderm: there is still almost no contact with uterine tissue. At 7 days 10 h amniotic folds are formed. Mesoderm appears occasionally but is not always present; when it appears it does not grow out from its place of origin. Entodermal cells, particularly in the proximal part of the extra-embryonic region, become polyploid. At the same time, the trophectoderm makes contact with the uterine decidua and gives rise to primary giant cells. Twelve hours later, the embryonic cells begin to degenerate, first in the region of the amniotic fold and the mesoderm. The embryo dies shortly afterwards. It is suggested that the primary target tissues affected by the Bld/Bld constitution are trophectoderm and entoderm. Many but not all of the abnormal features appearing later can by ascribed to insufficient nutrition of the embryo, due to failure of attachment of the trophectoderm and the filling of the yolk sac with entodermal cells.


Development of the segmental innervation of the chick forelimb.

A number of recent studies have shown that during embryonic development the initial innervation of a target structure may be made up, in part, by axons which do not form part of the mature innervation of that structure. In the present study we have examined the motor innervation of the major muscles of the chick forelimb at different stages of development using HRP-uptake-labelling of motoneurons, electrophysiological recording and measurement of muscle contraction. In the mature White Leghorn chick the major contribution to the motor innervation of the forelimb is from spinal segments 14, 15 and 16. Using the HRP-labelling technique we have shown that at stages 26-29 of development motoneurons in segments 12-17 have axon terminals in the presumptive biceps muscle. Between stages 30 and 35, however, the axon terminals arising from segments 12, 13, 16 and 17 are lost, leaving the mature innervation from segments 14 and 15. We have also observed the loss of innervation of the biceps muscle by segment 16 using electrophysiological recording of compound action potentials in the biceps nerve and by measurement of the local contraction of the biceps muscle in response to stimulation of the segmental nerves. Similar changes in the innervation of the triceps, extensor metacarpi radialis, flexor carpi ulnaris and flexor digitorum profundus muscles have also been observed. These results are discussed in relation to the hypothesis that (i) the motoneuron pools and muscles in the developing spinal cord and forelimb are matched, (ii) that some axons which arrive in a particular muscle during early development are unable to form a stable connexion and (iii) that the inability of an axon terminal to form a stable connexion in a muscle results in the death of the motoneuron. Intracellular recording from muscle cells at stage 35 shows that the synaptic site on each cell is innervated by about three separate axons. Over the next few stages, however, all but one of the innervating axons is lost. From our contraction studies it is clear that the removal of the excess axon terminals after stage 35 is not associated with the establishment of the mature segmental innervation pattern of the muscle.


Ventral horn cell counts in a Xenopus with naturally occurring supernumerary hind limbs.

In a Xenopus toad, two partially functioning supernumerary hind limbs developed naturally on the right side and were innervated by the ipsilateral side of the spinal cord. The number of ventral horn cells on the right was 18% higher than on the left while the combined mass of limb muscle on the right was estimated to be a 100% greater. This result corroborates studies with transplanted supernumerary limbs.


Autonomy of tendon development in the embryonic chick wing.

The aim of this study performed in the embryonic chick wing is to test the ability of the tendons to form and develop in the absence of the muscle bellies. The experiments were performed on 2-day chick embryos by destroying a portion of the somitic mesoderm by local X-irradiation. The irradiated part included the wing somite level 15-20 and extended three somites (or presumptive somites) in front and two to six presumptive somites in the rear of the wing somite levels. The wings of the operated side were examined histologically 3-8 days after the X-irradiation. The radio-destruction of the somitic mesoderm totally inhibited or severely impaired the development of the forearm muscles. But, despite the absence of the flexor and extensor muscles the differentiation of the distal manus tendons could be observed. This differentiation occurred at the same time and in the same positions as in controls. However, these tendons were transient structures. They disappeared within three days after their individuation. Two mechanisms that progressed in proximo-distal direction were involved in their resorption: cellular dislocation and cell death. We conclude that tendons start to develop autonomously from the muscle bulks, but for their maintenance and further development they require connexion to a muscle belly.


Adenylation and ADP-ribosylation in the mouse 1-cell embryo.

The incorporation of [3H]AAadenosine into cold trichloroacetic acid (TCA) insoluble material by the mouse 1-cell embryo has been studied. Incorporation of label was high immediately after fertilization, then decreased over the next 7 h with the sharpest decline occurring 3-5 h after fertilization. A small maximum was observed at the time of pronuclear DNA synthesis. Actinomycin D at a concentration which inhibited the cleavage of 1-cell embryos by 50% had little effect on this incorporation, which in the period 1-6 h post-fertilization was shown by autoradiography to be confined to the ooplasm of the newly fertilized ovum. [3H]Adenosine and poly ([3H]A) were released from embryo RNA labelled 1-3 h after fertilization with [3H]adenosine by digestion with a mixture of ribonucleases A and T1. The poly ([3H]A) segments were hydrolysed by alkali to 3'-[3H]AMP and [3H]adenosine ([3H]AMP/[3H]adenosine = 5/1), and by snake venom phosphodiesterase to 5'-[3H]AMP but very little [3H]adenosine. These results suggest that adenylation of RNA occurs soon after fertilization, that this is a cytoplasmic event, and that most of the newly synthesized poly ([3H]A) segments are joined to pre-existing poly (A) tracts. The unusual polynucleotide, poly (ADP-ribose), identified by its resistance to alkali and the release of 2'-(5''-phosphoribosyl)-5'[3H]AMP on incubation with snake venom phosphodiesterase, was also found in the ribonuclease digest.


A mutant of Tetrahymena thermophila with a partial mirror-image duplication of cell surface pattern. I. Analysis of the phenotype.

Cells of a mutant clone, CU-127, of Tetrahymena thermophila (formerly T. pyriformis, syngen 1) manifest three anatomical abnormalities. First, the stable number of ciliary meridians is 21-25, above the usual number (17-21) in this species. Second, up to 30% of the cells have two oral apparatuses (OAs), one normal and the other abnormal. Third, more than one-half of the cells possess two distinct sets of contractile vacuole pores (CVPs). In some living cells two contractile vacuoles are seen. These abnormalities have persisted unchanged during more than 500 generations of vegetative propagation, and are similarly expressed in subclones. The normal and abnormal OAs are topographically segregated, with normal OAs developing along the "primary oral axis" and abnormal OAs developing along a "secondary oral axis" that is situated 170 degrees of the cell circumference to the cell's right of the primary oral axis. CVPs always appear within this 170 degree arc and never within the complementary 190 degrees arc to the left of the primary oral axis. A unique feature of the CU-127 clone is the commonly expressed mirror image reversal of the structural pattern of OAs that develop along the secondary oral axis. The primordia of such OAs initially appear (as usual) to the cell's left of a ciliary meridian, but as membranelles develop the frequently come to be oriented in a mirror image of the normal pattern, and an undulating membrane sometimes develops on the wrong (left) side of the oral primordium. When two sets of CVPs are formed, their average positions are roughly equidistant with respect to the two oral axes, with the two sets located 50-60 degrees to the right and left respectively of the primary and secondary oral axis. Such cells are thus bilaterally symmetrical about a plane defined by the central longitudinal axis and the halfway point between the two CVP sets (see Fig. 25). This plane bisects the cell into a normal and a "reversed" half-cell. However, only oral asymmetry and large-scale CVP positioning are subject to such reversal; all ciliary meridians remain of normal asymmetry and all CVPs are situated on the left side of CVP meridians. The fact that major aspects of large-scale cellular organization can be reversed while the "fine-positioning" associated with the ciliary meridians remains normal indicates that the two aspects of cell organization are distinct.


Culture of early somite mouse embryos during organogenesis.

Early somite (2-4) mouse embryos were explanted and then maintained in culture for 24 or 48 h intervals. Various types of media were tested and it was determined that rat serum supported normal growth over a period of 48 h, based on total protein analysis and histological comparisons with in vivo specimens. Other media including fetal calf serum and fetal calf serum and Waymouth's (1:1) supported some growth, but did not equal the success of using rat serum alone. During the 48 h culture period in rat serum, embryos developed to stages indistinguishable from embryos maintained for a similar time in vivo.


A mutant of Tetrahymena thermophila with a partial mirror-image duplication of cell surface pattern. II. Nature of genic control.

The CU-127 clone of Tetrahymena thermophila, which manifests an unusually high number of ciliary rows plus a second set of abnormal oral structures and of contractile vacuole pores with partial mirror-image reversal of asymmetry (Jerka-Dziadosz & Frankel, 1979), has been subjected to breeding analysis. The progeny ratios obtained in various crosses indicate that the abnormalities of cell-surface asymmetry are brought to expression as a result of the action of a recessive allele at a single gene locus, here named janus. When previously normal cells were made homozygous for the jan allele, the cortical pattern characteristic of the CU-127 clone came rapidly to expression, often without associated change in number of ciliary meridians. Conversely, when cells previously expressing jan re-acquired the wild-type (jan+) allele, they returned to the normal pattern of a single normal oral structure and a single normally located set of contractile vacuole pores while still retaining the high ciliary meridian number characteristic of the original CU-127 clone. The capacity for manifestation of the unique asymmetry pattern depends solely on homozygous expression of the janus allele, whereas the stable number of ciliary meridians in janus clones and the degree of expression of secondary OAs is modulated by other factors, probably at least in part genic. These results, taken together with those of the preceding paper, indicate that the janus allele promotes the propagation and/or expression of a condition of reversed asymmetry in a precisely located cell region, and further indicates that the propagation and expression of this condition are largely independent of the number and asymmetry of ciliary meridians.


Duplicated axolotl regenerates.

Three series of palette stage regenerates were prepared by amputating both arms of juvenile axolotls in the mid-forearm, above the elbow, or close to the shoulder. Within each series, excised regenerates were replaced in their original orientation (as a control) or rotated at 90 degrees intervals about the proximodistal axis, or were transplanted to the contralateral arm with identical rotations. Control grafts occasionally caused the formation of a single extra digit. All experimental rotations provoked duplicate or triplicate structures, ranging from accessory digits to extra forearms. Shoulder level grafts were subject to a pronounced correctional derotation and yielded a variable proportion of duplications. Forearm and elbow-level rotations invariably yielded duplications, which therefore result from an axial discrepancy rather than complete axial opposition between graft and host. These results are incompatible with the clockface model of positional information and demand a modification of other current models. The recorded frequency and orientation of duplications suggest that a limb contains at least two polarized transverse axes which cannot be respecified during regeneration. A substantial discrepancy on either axis reduces the normal regulative interaction between graft and host, allowing either of them to regenerate independently.


A study of digit fusion in the mouse embryo.

During the embryonic development of the mouse limb separation of the digit is followed by their union. This is a true, though temporary, epithelial fusion, a fused layer of epidermal cells remaining intact until separation takes place after birth. The periderm cells in the line of fusion are displaced to the dorsal or ventral surface of the foot. On the dorsal surface these displaced cells form a prominent interdigital ridge of elongated, intertwined cells which remains until the periderm is shed. During the fusion of the eyelids, and also of the pinnae to the scalp, a similar ridge of periderm cells is formed.


Post-embryonic determination of the ecdysial line in the cockroach: evidence for pattern regulation in the medio-lateral axis.

By removing or transplanting sections of the ecdysial line in the cockroach Gromphadorhina portentosa, pattern regulation in medio-lateral axis of an insect has been demonstrated. The line can reform after sections have been removed and when epidermal grafts from either side of the midline are grafted with confronting medial edges. The results are explicable in terms of known mechanisms for pattern regulation in insects.


Formation and consequences of cell patterns in preimplantation mouse development.

The behaviour of groups of cells was studied in culture during preimplantation mouse development. The following observations were made with intact embryos minus the zona pellucida and with embryos whose cells had been dissociated and recombined. The form of the 4-cell embryo was related to the behaviour of the first cell to divide to this stage. The form of the 8-cell embryo depended on contact between the groups of four cells each derived from a single cell at the 2-cell stage. The form of the 16-cell embryo depended on cell movement during and after division from the 8- to the 16-cell stage. These results suggest that the morphogenetic movements of these early embryonic cells are principally governed by continuous cell interactions after fertilization. The cell surfaces of the embryos were examined with scanning electron microscopy in an attempt to discriminate between the mechanisms which could account for these movements.


The influence of local environment on the organization of mesenchyme cells.

Limb, somite, and neural crest mesenchyme from quail embryos were implanted orthotopically and heterotopically into chick hosts to ascertain the relative importance of the local environment on mesenchyme migration. It was found that mesenchyme behavior is strongly influenced by the environment. Normally non-migratory, limb mesenchyme is capable of spreading like sclerotome when placed in the somite region. A somite placed in the limb acquires an appearance typical of limb mesenchyme. Neural crest placed in the limb migrates only along the co-implanted neural tube or axons growing out from it. The orthotopic transplantations showed that quail mesenchyme behaves normally in chick embryos. Furthermore, it was observed in the orthotopic transplants that there was no intermingling of quail and chick cells even at the edge of the graft. This result indicates that cells within mesenchyme are normally not locomotory; rather, the mesenchyme "migrates" by spreading and expansion of the tissue as a unit in response to local influences.


The influence of the lower beak on the interorbital septum-prenasal process complex in the chick embryo.

The effect of removal of the lower beak on the development of the interorbital septumprenasal process (ISPP) complex was studied in chick embryos. In normal development the angle between the ventral contour of the interorbital septum and the long axis of the prenasal process increases. At the same time the angle between the ventral contour of the interorbital septum and the basal plate increases. After surgical removal of the prospective lower beak at stage 29, the position of the entire ISPP complex was altered in stage-38 embryos and the prenasal process showed elongation. In stage-38 embryos in which the prospective upper beak had been removed at stage 29, Meckel's cartilage was elongated. It is concluded that straightening of the angle between the ventral contour of the interorbital septum and the long axis of the prenasal process is not influenced by the lower beak, whereas the position of the entire ISPP complex and the size of the prenasal process are under the epigenetic influence of the lower beak. The position and size of Meckel's cartilage are under the epigenetic influence of the upper beak.


Monomeric and aggregate proteoglycans in the chondrogenic differentiation of embryonic chick limb buds.

Proteoglycan heterogeneity was studied during the in vivo differentiation of embryonic chick limb cartilage. Recently, it has been shown that during the differentation of limb cartilage the proportion of the aggregated form of proteoglycans increases whereas the unassociated monomeric forms decrease, and this has been related to the synthesis of two link proteins at a specific stage of differentation. In this study it is suggested that the appearance of the aggregate formation is also due to synthesis of a stable hyaluronic acid binding region of the core protein. Thus, it can be concluded that differential gene expression for these proteins takes place as a differentiation phenomenon.


Role of the somitic mesoderm in the development of the thorax in bird embryos. II. Origin of thoracic and appendicular musculature.

The regional embryonic origin of trunk and limb musculature was determined through heterospecific homotopic or heterotopic transplantations of quail somitic or somiticsomatopleural mesoderm into chick hosts, and through localized X-irradiation of the somitic mesoderm. Experiments were performed on 2-day embryos. Results show that the myoblastic component of all truncal and appendicular muscles is of somitic origin. Intra- and perimuscular connective tissue as well as tendons are of somatopleural origin. X-ray destruction of the somitic mesoderm at and beyond the wing level resulted in the complete or almost complete absence of musculature in the wing and corresponding truncal region. The mapping of the cephalocaudal origin of the various muscles was found to be as follows: Intrinsic and extrinsic muscles of the wing and scapular girdle Somites 12-20 Grand pectoral muscle Somites 12-22 Intercostal muscles Somites 19-26 Abdominal muscles Somites 27-29 Intrinsic and extrinsic muscles of the leg and pelvic girdle Somites 26-32 Dorsal and intervertebral muscles Metameric level, specific origin In the heterotopic transplantations, the grafted somitic mesoderm gave rise to site-specific morphogenesis, irrespective of the cephalocaudal level of its origin. This result demonstrates that, at 2 days of incubation, the myogenic somitic cells are not regionalized.


H-2 I-region encoded targets in allograft rejection.

Fresh thyroids transplanted to I-region disparate recipients are, in most cases, rejected; in some instances fresh thyroids undergo periods of crisis followed by functional recovery. Cultured thyroids that are taken from donor animals pretreated with lymphocytotoxic drugs, gamma radiation and cultured for 10 d in vitro are not rejected by any normal allogenic recipient. If the recipient is sensitized with lymphoid cells syngeneic with an I-region disparate cultured thyroid donor, the cultured thyroid is rejected if I-A-subregion differences are included. We interpret these data to indicate that there exist I-region encoded perenchymal cell target determinants which are not, by themselves, immunogenic.


Time-dependent localization of arsenic in subcellular liver fractions.

In an effort to assess previously reported localization of arsenic within the hepatocyte nucleus (determined on the basis of increases in the percent of nuclei containing inclusion structures as time of exposure to arsenic increased) (Sorensen, 1976c), cell separations were conducted on fish livers following in vivo exposures identical to those previously reported. Green sunfish were exposed to 60 ppm arsenic for 2, 4, or 6 days prior to homogenation and subfractionation of the liver for arsenic determinations by neutron activation analysis. Mean percent arsenic in the soluble cytoplasmic fraction decreased significantly from 46 to 28 to 17 percent in 2, 4, or 6 days, respectively; whereas arsenic in the nuclear and cell residue fraction increased significantly from 12 to 42 to 58 percent during the same time period. All subfractions were found to contain homogeneous populations of subcellular organelles.


Direct evidence that natural killer cells in nonimmune spleen cell populations prevent tumor growth in vivo.

Relatively large numbers of nonimmune spleen cells do not protect against the local growth of two lymphomas. However, this heterogeneous population of splenic lymphocytes contains a subset of cells that efficiently protects against in vivo tumor growth. This cell population (cell-surface phenotype Thyl.2(-)Ig(-)Ly5.1(+)) represents less than 5 percent of the spleen cell population and is responsible for in vitro NK-mediated lysis. Although these studies clearly and directly demonstrate that Ly5(+) NK cells selected from a heterogeneous lymphoid population from nonimmune mice can protect syngeneic mice against local in vivo growth of two different types of tumor cells (in contrast to other lymphocyte sets within the spleen), they do not directly bear upon the role of NK cells in immunosurveillance. They do indicate that highly enriched Ig(-)Thyl(-)Ly5(+) cells, which account for virtually all in vitro NK activity, can retard tumor growth in vivo. It is difficult to ascribe all anti-tumor surveillance activity to NK cells, because they probably do not recirculate freely throughout the various organ systems of the body. Perhaps NK ceils may play a role in prevention of neoplastic growth within discrete anatomic compartments where there is rapid differentiation of stem cells to mature progeny (e.g., bone marrow, spleen, and portions of the gastrointestinal tract)and may normally act to regulate the growth and differentiation of non-neoplastic stem cells. Long-term observation of chimeric mice repopulated with bone marrow from congenic or mutant donors expressing very low or very high NK activity may help to answer these questions.


Immune phagocytosis in murine malaria.

Spleen macrophages from Plasmodium berghei-infected mice are more efficient in the ingestion of parasitized reticulocytes than spleen macrophages obtained from normal animals. Other indications of spleen macrophage activation detected during malarial infection are enhanced macrophage spreading and increased phagocytosis of opsonized and nonopsonized sheep erythrocytes (E). Peritoneal macrophages are not activated to a significant degree. The appearance of antibodies directed against Forssman antigen, but not to other erythrocyte antigens, is also a feature of this infection and explains the ingestion of unsensitized E by spleen macrophages of the diseased animals. The recognition and ingestion of parasitized reticulocytes by infected mice in mediated by cold-agglutinin type immunoglobulins that appear during P. berghei infection and can be blocked by the Fc-binding protein A from Staphylococcus aureus. In advanced stages of the disease, the serum of infected animals inhibits phagocytosis, probably because of the high level of circulating immune complexes. Thus, the clearance of malaria parasites is regulated by several elements of the immune system, in addition to levels of specific antimerozoite antibodies, including the amount of antibodies bound to reticulocytes, the presence of circulating immune complexes, and the degree of macrophage stimulation.


The influence of steroid hormone metabolites on the in vitro development of erythroid colonies derived from human bone marrow.

Certain C19 and C21 steroid metabolites, when incubated with normal human bone marrow cells in culture, increased the number of erythroid colonies in the presence of erythropoietin. Among a number of pairs of C5 epimeric steroids tested, most 5beta (A:B cis) steroids stimulated the growth of both early erythroid progenitor cells (BFU-E) and late erythroid progenitor cells (CFU-E), whereas only a few 5alpha-(A:B trans) steroids stimulated the growth of CFU-E. No 5alpha-compounds of six pairs of steroids studied were found to stimulate BFU-E formation. This structure-activity relationship conforms with that previously observed in studies of steroid induction of ALA-synthase in avian embryo liver cells and hemoglobin synthesis in the cultured avian blastoderm. When human bone marrow cells were preincubated with the steroids for 2 d, followed by incubation with erythropoietin, only the 5 beta-compounds stimulated the growth of BFU-E. Similarly, when addition of steroids was delayed in relation to erythropoietin in the culture, only the 5 beta-derivative of a pair of C5 epimeric compounds displayed an enhancing effect on the growth of BFU-E. This effect required that the steroid addition be made no later than 48 h after initiation of the culture. These data demonstrate that certain natural steroid metabolites significantly stimulate erythropoiesis in normal human bone marrow cells in culture. They also indicate that 5 beta-compounds are more stimulatory than their 5 alpha-epimers, and they suggest that these 5 beta-steroids act preferentially on very primitive erythroid progenitor cells, probably on BFU-E.


Evidence for two homologous, but nonidentical, Ia molecules determined by the I-EC subregion.

Sequential immunoprecipitation, two-dimensional gel electrophoresis and peptide mapping analyses of B10A(3R), 35S-methionine-labeled, I-EC subregion products were performed. Evidence is presented here for the presence of two structurally homologous, but nonidentical, gene products of the I-EC subregion. These two Ia molecules are independently immunoprecipitable, identical in molecular size and charge, but differ by approximately equal to 20% in their peptides obtained by partial digestion with Staphylococcus aureus protease V8.


Release of arachidonic acid from human lymphocytes in response to mitogenic lectins.

After exposure to mitogenic lectins in vitro, human mononuclear cells (95% lymphocytes) that had been prelabeled with [14C]arachidonic acid rapidly released a portion of their radioactivity in the medium. Most of the released radioactivity was demonstrated to be free arachidonic acid. Although other sources are not excluded, the most important source of cell-bound radioactivity in the release reaction appeared to be phosphatidylinositol, suggesting that at least part of the response is occurring through an increase in phospholipase A2 activity. By gas liquid chromatography, other fatty acids were also shown to be released, but there was considerable selectivity in the response for arachidonic acid. The response was dependent on the availability of free Ca++ in the medium and was enhanced by serum proteins and unlabeled arachidonic acid. Most of the response appeared to be from the the lymphocytes themselves rather than from contaminating cells. The rapid generation of free arachidonic acid in response to mitogenic lectins suggests a possible role for arachidonic acid metabolites in the activation process.


Origin, Kinetics, and characteristics of pulmonary macrophages in the normal steady state.

Pulmonary macrophages of mice in the steady state were isolated by lavage with PBS containing EDTA and subsequent enzymatic digestion of tissue with pronase and DNA-ase. By this method, the total pulmonary macrophage population was obtained in two cell suspensions, one with a pure population of pulmonary alveolar macrophages (PAM) and the other with a mixed population of pulmonary alveolar and pulmonary tissue macrophages (PTM). The morphological, cytochemical, and functional characteristics of both PAM and PTM were like those of mature tissue macrophages except for the presence of C3 receptors. These receptors were almost absent on PAM and present on a larger number of cells in the mixed population of PAM and PTM. The total pulmonary macrophage population of mice in the steady state is approximately equal to 2 x 10(6), of which about 93% are PAM and about 7% are PTM. In labeling experiments with 3H-thymidine, the low in vitro labeling indices (less than 3%) for both PAM and the mixture of PAM and PTM, showed that both are essentially nondividing cells. In vivo labeling studies showed an increase in the number of labeled macrophages that can only be attributed to labeled monocytes migrating into the lungs. Additional evidence was provided by a decrease in the labeling indices of pulmonary macrophages when mice were treated with hydrocortisone acetate, which causes a severe monocytopenia, thus preventing monocyte influx into the lungs. Confirmation of the bone marrow origin was obtained in mice labeled after x-irradiation with partial bone marrow shielding: labeled pulmonary macrophages were found in the exposed lungs. In all experiments, the labeling indices were identical in the two macrophage populations isolated. These results show that the influx of monocytes is the source of cell renewal for the pulmonary macrophages. No indications for an interstitial division or maturation compartment in the lung were found. Quantitation of the efflux of labeled monocytes from the blood, and the number of labeled pulmonary macrophages, showed that in the steady state about 15% of the monocytes leaving the circulation become pulmonary macrophages and that the turnover time of pulmonary macrophages is approximately equal to 27 d.


In vitro metabolism of the anabolic drug zeranol.

The anabolic drug zeranol, which is employed for livestock breeding was studied for its metabolic fate in vitro using isolated microsomal preparations from bovine liver, uterus, and muscle. Diethylstilbestrol and 17 beta-estradiol were investigated simultaneously for comparison. The structure of the zeranol metabolite was examined by means of TLC as well as GC-MS analysis. A sensitive color reaction after two-dimensional TLC described earlier for zeranol determination in veal samples is proposed for the detection of the zeranol metabolite zearalanone and the mycotoxin zearalenone. The estrogenic activity of the three mycoestrogens, understood as their binding capacity to the cytoplasmic estrogen receptor protein from bovine uterus, is measured using the estrogen receptor test. The data suggest that zeranol is biotransformed in vitro to a less active estrogen which has a marked similarity to the mycotoxin zearalenone. Further investigations are necessary to quantitate the biotransformation in vitro as well as to evaluate the toxicity of the drug metabolite.


Friend erythroleukemia antigen. A viral antigen specified by spleen focus-forming virus and differentiation antigen controlled by the Fv-2 locus.

Serum from C57BL/6 (B6) mice hyperimmunized with NB-tropic Friend virus complex (FV) was cytotoxic for FV-induced erythroleukemic spleen cells and B6 Friend-murine leukemia virus (F-MuLV) lymphoma cells. Cytotoxic activity for erythroleukemia cells remained after repeated absorption of B6 anti-FV antiserum with Friend-Moloney-Rauscher MuLV lymphoma cells but was removed by absorption with erythroleukemia cells induced by FV or Rauscher Vrus. This serologic test system identified a previously unrecognized cell-surface antigen of mouse leukemia, designated Friend Erythroleukemia (FE) antigen to signify its appearance as a determinant of virally induced erythroleukemic differentiation. FE antigen was not detected on 15 transplanted or primary hematopoietic neoplasms, nor was it detected on cells infected with ecotropic, xenotropic, or dualtropic MuLV isolates in tissue culture. Two spleen focus-forming virus (SFFV) nonproducer cells of rats and one of mice express FE antigen in amounts comparable to primary erythroleukemia cells. Absorption tests with FE typing serum indicated that FE antigen was expressed on bone marrow and spleen but not thymus, lymph node, or peripheral blood of uninfected AKR, BALB/c, DBA, and SWR mice; all five tissues from B6 and C57L were negative. Quantitiative absorption tests indicated that the expression of FE antigen, though much lower than on erythroleukemic cells, was greatest on fetal liver, less on bone marrow, and lowest on spleen from BALB and SWR mice. Treatment of BALB/c or SWR fetal liver, bone marrow, spleen, thymus, or lymph node cells with FE typing serum did not result in significant lysis. These observations are consistent with the interpretation that FE antigen is expressed by a minor cell population present in fetal liver, bone marrow, and spleen. Expression of FE antigen, determined by absorption with bone marrow cells, cosegregated with inheritance of the Fv-2s allele in the 17 inbred, 7 recombinant inbred, and 4 congenic mouse strains tested. In summary, the FE antigenic system identifies a cell-surface determinant that has the properties of a SFFV-specified antigen and hematopoietic differentiation alloantigen controlled by the Fv-2 locus. The similarity of FE antigen to Abelson antigen may provide insight into the pathogenic properties of defective transforming MuLV.


Cytokinetic analysis of the impaired proliferative response of peripheral lymphocytes from aged humans to phytohemagglutinin.

The effect of donor age on the rate of cell entry into the proliferating pool and subsequent cell cycle duration for peripheral lymphocytes stimulated by phytohemagglutinin (PHA) were examined by using the bromodeoxyuridine incorporation-differential staining technique. Distribution curves for the appearance of metaphase cells in successive generations as a function of culture time were obtained and analyzed both graphically and by a computer simulation model. Peripheral lymphocytes from aged individuals (approximately 75 yr) were stimulated by PHA at approximately one-half of the rate of peripheral lymphocytes from young individuals (approximately 21 yr). Subsequent cell-cycle durations were estimated to range from 10.0 to 25.0 h for aged individual lymphocyte cultures and 10.6-15.6 h for young individual lymphocyte cultures. The possible significance of these findings to aging in general is discussed.


Clinical presentation and management of patients with carcinoma of the lung: a 14-year experience.

Carcinoma of the lung has been steadily increasing since World War II, and the family physician can now expect to see a greater incidence of the disease in women and persons under age 50 years. The clinical manifestations of carcinoma of the lung are described, based on a 14-year experience at the University of Michigan. Diagnostic procedures are outlined. The preferred treatment for carcinoma of the lung is pulmonary resection, combined, in appropriate situations, with mediastinal lymph node irradiation. Survival is dependent to some degree on the tumor cell type as well as the extent of metastasis. A new immunotherapeutic adjunct to resection and irradiation is being developed. Five to ten-year survivors of resections for lung cancer and normal persons serve as lymphocyte donors. Transfer factor is extracted from these lymphocytes and injected into selected patients who have recently had resections for lung cancer. It is too soon to evaluate the results of this experiment, but it is hoped that immunotherapy using transfer factor will be of help to patients with carcinoma of the lung.


Indications and risk-benefit of mammography.

Mammography has recently undergone a striking improvement in image detail along with a corresponding decrease in radiation exposure. Although the data of the Breast Cancer Detection Demonstration Project is tainted by an absence of a control group of women, the high rate of detection of early cancer by mammography alone in the participants above or below age 50 years implies that mammography is useful in detecting breast cancer before the appearance of a palpable mass. Early diagnosis results in higher survival rates. Mammographers should continuously seek the least radiation exposure consistent with a sharp image. Given present knowledge of its benefit and potential risk, mammography should be performed when a significant suspicion of breast cancer exists at any age, but it should not be performed under age 35 years without such suspicion. A baseline mammogram should be performed in the 35 to 40-year age group. The periodicity of survey mammography in asymptomatic women under 50 years should be determined by analysis of relative risk factors for breast cancer. For asymptomatic women age 50 years and older, periodic screening mammography is sound medical practice.


Applicability of crisis intervention in family practice.

Crisis intervention is a specialized approach useful to family physicians who frequently are called upon to deal with patients in psychosocial crisis. The use of a systematic method of evaluation and treatment will aid physicians in helping patients with their problems in a fashion that is constructive for both patient and physician. A crisis may occur as a result of a change in an important social role or relationship. Appropriate intervention which is immediately available can result in a marked reduction in physical and emotional symptoms that are stress related. This paper reviews the need for crisis intervention, its historical development, theory and technique, and several examples of crises familiar to all family physicians. A case illustration is presented as a demonstration of crisis intervention in family practice.


Accidents as a symptom of alcohol abuse.

This review of the literature on the association between accidents and alcohol abuse presents data from a variety of studies performed in many of the industrial nations of the world. These studies demonstrate a consistent relationship between alcohol abuse and accidents. The family physician should be aware of this association and utilize it in the identification and treatment of his alcoholic patients.


Does continuing medical education improve the quality of medical care? A look at the evidence.

Although continuing education has a long tradition within the medical profession, mandated continuing medical education is of very recent origin. The conceptual framework used to justify continuing medical education is that it exposes physicians to new knowledge, changes physician behavior, and favorably alters patient outcomes. Considerable evidence exists that physician knowledge can be increased, and that behavior can be changed, but there is very little to show an effect on patient outcomes. The effectiveness of continuing medical education is further clouded by such issues as consumerism, licensure politics, and professional standards review organization legislation. Family physicians should have a role in determining the outcome of the continuing medical education debate, as participants, as policy-setters, and as informed critics.


Family care in a family practice group.

A fundamental claim of family medicine is that the family physician treats the "whole" family--an ideological principle that guides undergraduate and residency education. Using archival data obtained from a random sample of 500 patients in one group of family physicians, this study analyzed the extent to which this principle is carried out in practice. Physicians trained in family practice residency programs were compared with their colleagues. Family types and marital stability were also examined. Results indicate that in only 28 percent of families (excluding single person households) were all family members seen by the same family physician. This occurred despite the high preponderance and stability of traditional nuclear families in the practice. There was no significant difference in this rate between graduates and nongraduates of approved family practice residency programs.


Regeneration and compartments in Drosophila.

A clonal analysis was performed in order to study the process of regeneration in wounded wing discs of Drosophila. Regeneration was induced either by cutting the disc in situ, or by shifting gynandromorphic larvae whose male tissue was hemizygous for a temperature-sensitive cell lethal to the restrictive temperature. Fast growing M+ clones, labelled with y and/or mwh, were produced by X-irradiation of the following genotypes: y; scJ4(y+)M(3)i55/mwh jv M+ (series I), and l(1)ts 504 sn3 l(1)ts 5697/ In(1)wvC; M(3)i55/mwh M+ (series II). The clones were induced either before or after the experimental lesion. Clones initiated one day prior to the lesion were able to cross compartment boundaries whereas clones initiated one day after the lesion did not do so. It is concluded that cells involved in the process of regeneration lose their compartmental commitment, but that later on the growing population of cells again becomes subdivided into the same compartments.


Mutagenicity test with saccharin in the male mouse.

The ability of saccharin to induce chromosome aberrations in mammals was tested in male mice injected i.p. with 1, 2, or 4 g saccharin per kg body weight or receiving during a 100 day period 20 g of saccharin per liter of drinking water. Two tests on somatic cells, induction of chromosomal aberrations in bone marrow cells and of micronuclei in polychromatic erythrocytes, and two tests on germ cells, the spermatocyte test on treated males and the dominant lethality test, yielded all negative results. It is concluded that the positive findings reported in the literature were probably due to the mutagenic activity of saccharin impurities.


Biological activity in vitro of chrysotile compared to its quarried parent rock (platy serpentine).

Crushed serpentine rock, quarried at Rockville, Maryland, has been used in large quantities for road and playground surfacing. The rock consists essentially of the fibrous serpentine mineral chrysotile (asbestos) and platy serpentines. In vitro bioassay in P338D1, a malignant mouse macrophage-like cell line, show that chrysotile is cytotoxic while the platy serpentines are not.


Prescribing patterns in a family medicine residency program.

The methodology and results of a concurrent review of prescribing practices in a family practice residency are discussed. A clinical pharmacist reviewed copies of prescriptions returned to him during a six-month period, and he tabulated information to allow comparisons of clinic prescribing patterns with national patterns. Additionally, peer group comparisons within the residency were made. It was found that tricyclic antidepressants were prescribed more frequently than anxiolytic drugs, a distinct difference when compared to national prescribing reports. Peer group comparisons showed apparent autonomy in prescribing habits among residents and faculty, and the drug "repertoire" and number of prescriptions written increased as the number of years in the residency progressed.


The impact of disease prevalence on the predictive value of laboratory tests in primary care.

The predictive value of any diagnostic process is related to the sensitivity and specificity of the test and the prevalence of the underlying pathology for which the diagnostic testing is accomplished. Prevalence is the most important, but least understood, factor affecting the usefulness of a test result. For each accomplished test which is not helpful in either supporting a diagnosis or assisting in a differential diagnosis, the health care cost is increased without a corresponding benefit in the value of the information obtained.


The relationship of health beliefs and a postcard reminder to influenza vaccination.

The relationship of certain health beliefs to influenza vaccination and the effect of a postcard reminder on vaccination rates was studied among 232 high-risk patients. In agreement with the Health Belief Model tested, the patients vaccinated believed influenza to be more serious, believed they were more susceptible to influenza, and believed the vaccine to be more efficacious than did patients not vaccinated. Those not vaccinated were less satisfied with their medical care and felt the vaccine was more expensive than those vaccinated. A postcard reminding patients of influenza vaccination was an effective way to increase the vaccination rate. Patients receiving the card had a 59.7 percent vaccination rate compared to a 30.0 percent rate among those not receiving the postcard. This study suggests that a reminder postcard is an effective means to promote influenza vaccination and that these beliefs are important determinants of vaccination behavior.


Cryotherapy of the cervix.

Cryotherapy is most useful in treating mild and moderate dysplasia of the ectocervix and symptomatic benign chronic cervicitis. It has almost replaced electrocauterization of the cervix and has reduced the need for conization. Cytology and colposcopy are essential in the selection of patients for this procedure and in evaluating their response to therapy.


Ultrastructure of normals and castrates and the effects of testosterone and ultraviolet (UVL-B) irradiation on scrotal skin of rats.

The ultrastructure of the testosterone dependent epidermal melanocyte system of the scrotal skin of normals and castrates, with and without testosterone replacement therapy, and UVL-B (280-315 nm) radiation in black Long Evans rats is reported. UVL-B increases melanocyte activity, melanosome forming apparatus, (size of Golgi zone and RER, and quantity of cytoplasmic vesicles, dendrites, and stages of melanosomes) in normals and in castrates. Testosterone replacement therapy to castrates is not a prerequisite for stimulation by UVL-B, but it enhances the effects of UVL-B without restoring normalcy as melanosome packaging into complexes predominates. After UVL-B stimulation of normals or castrates, melanocyte dendrites are observed more often. Melanocyte dendrites of skin of castrated rats are observed less often than in normals, but with testosterone replacement therapy, the dendrites become more numerous. Melanosomes donated to keratinocytes are mostly located as singles in normals and as complexes in castrates. After UVL-B, castration, or testosterone replacement therapy, the melanosomes are packaged in keratinocytes in complexes larger than in normals. In the epidermis of long term castrates (9-109 days), non-specific clear cells are observed and Langerhans cells containing melanosomes; we did not observe them in normals. Melanocytes of castrates have a reduced melanosome forming apparatus. The dermis of castrates contains many dermal melanocytes in the superficial dermis with melanosomes in several stages of formation. These cells are not apparent in normals at this location in the dermis. Testosterone replacement therapy and/or UVL-B administered to castrates does not restore the epidermal melanocyte system nor the dermis to precastration ultrastructural appearance; castration has a permanent altering effect as melanosomes are packaged into complexes.


Effects of ouabain on fluid transport and electrical properties of Necturus gallbladder. Evidence in favor of a neutral basolateral sodium transport mechanism.

Net fluid transport (Jv) and electrical properties of the cell membranes and paracellular pathway of Necturus gallbladder epithelium were studied before and after the addition of ouabain (10(-4) M) to the serosal bathing medium. The glycoside inhibited Jv by 70% in 15 min and by 100% in 30 min. In contrast, the potentials across both cell membranes did not decrease significantly until 20 min of exposure to ouabain. At 30 min, the basolateral membrane potential (Vcs) fell only by ca 7 mV. If basolateral Na transport were electrogenic, with a coupling ratio (Na:K) of 3:2, the reductions of Vcs at 15 and 30 min should be 12--15 and 17--21 mV, respectively. Thus, we conclude that the mechanism of Na transport from the cells to the serosal bathing solution is not electrogenic under normal transport conditions. The slow depolarization observed in ouabain is caused by a fall of intracellular K concentration, and by a decrease in basolateral cell membrane K permeability. Prolonged exposure to ouabain results also in an increase in paracellular K selectivity, with no change of P Na/P Cl.


Inactivation of the alamethicin-induced conductance caused by quaternary ammonium ions and local anesthetics.

Long alkyl chain quaternary ammonium ions (QA), the local anesthetics (LA) tetracaine and lidocaine, imipramine, and pancuronium cause inactivation of the alamethicin-induced conductance in lipid bilayer membranes. The alamethicin-induced conductance undergoes inactivation only when these amphipathic compounds are added to the side containing alamethicin. The concentration of QA required to cause a given amount of inactivation depends on the length of the hydrocarbon chain and follows the sequence C9 greater than C10 greater than C12 greater than C16. LA and imipramine, in contrast to QA or pancuronium, are able to promote appreciable inactivation only if the pH of the alamethicin-free side is equal to or lower than the pK of these compounds. The membrane permeability to QA, LA, or imipramine is directly proportional to the alamethicin-induced conductance and is larger than the one for potassium. The observed steady state and time-course of the inactivation are well described by a model similar to that proposed by Heyer et al. (1976. J. Gen. Physiol. 67:703--729) and extended for any value of the diffuse double layer potential and for LA and imipramine. In this model QA, LA, or imipramine are able to permeate through the membrane only when the alamethicin-induced conductance is turned on. The amphipathic compounds then bind to the other membrane surface, changing the transmembrane potential and turning the conductance off. For a given concentration of QA, LA, or imipramine the extent of inactivation depends on two factors: first, the binding characteristics of these compounds to the membrane surface and second, their ability to permeate through the membrane when the alamethicin-induced conductance is turned on. The several possible mechanisms of permeation of the amphipathic molecules tested are discussed.


Transmembrane effects of irreversible inhibitors of anion transport in red blood cells. Evidence for mobile transport sites.

Experiments were designed to determine whether band 3, the anion transport protein of the red cell membrane, contains a mobile element that acts as a carrier to move the anions across a permeability barrier. The transport site-specific, nonpenetrating irreversible inhibitor 4,4'-diisothiocyano-2,2'-stilbene disulfonate (DIDS) was found to be effective only when applied extracellularly. It was used to sequester transport sites on the extracellular side of the membrane in intact cells. The membranes were then coverted into inside-out vesicles. The number of anion transport sites available on the cytoplasmic side of the vesicle membranes was then estimated by measuring the binding of N-(-4-azido-2-nitrophenyl)-2-aminoethyl-sulfonate (NAP-taurine), a photoreactive probe. Pretreatment with DIDS from the extracullular side substantially reduced the binding of NAP-taurine at the cytoplasmic side. Since NAP-taurine does not appear to penetrate into the intravesicular (normally extracellular) space, a transmembrane effect is apparently involved. About 70% of the DIDS-sensitive NAP-taurine binding sites are located in band 3, with the remainder largely in a lower molecular weight (band 4) region. A similar pattern of reduction in NAP-taurine binding is produced by high concentrations of Cl-, but this anion has little or no effect in vesicles from cells pretreated with DIDS. Thus the DIDS-modulated sites seem to be capable of binding either NAP-taurine or Cl. It is suggested that band 3 contains a mobile transport element that can be recruited to the extracellular surface by DIDS, thus becoming unavailable to NAP-taurine at the cytoplasmic face of the membrane. The results are consistent with a model of carrier-mediated transport in which the movement of the transport site is associated with a local conformational change in band 3 protein.


Social alienation-personal disorganization assessment in disturbed and normal adolescents.

Two groups of adolescents seeking psychotherapy (N = 91 and N = 198) and a normative group (N = 112) provided 5-minute verbal behavior protocols which were content analyzed for social alienation-personal disorganization (SA-PD). The data supported the hypothesis that adolescents applying for help in 1974 to 1975 showed greater pathology than those seen in 1972 to 1973. The normative adolescents were significantly healthier than either of the two Adolescent Clinic groups. In the clinic samples, older adolescents were more disturbed than those in the younger ranges. The SA-PD scale is a useful addition to tools available for the assessment of emotional states of adolescents. The data support the idea that there appears to be an increasing severity in the problems presented by adolescents in very recent years.


Neuropsychological test performance of normal, learning-disabled, and brain-damaged older children.

The performance of 75 brain-damaged, learning-disabled, and normal children aged 9 to 14 years was compared on 13 neuropsychological test measures. Analysis of variance, supplemented by t-tests, indicated a significant difference beyond the .01 level on 11 measures and beyond the .05 level on one measure. A discriminant analysis based on weightings of the 13 measures yielded 80 per cent correct classification of subjects, a finding in agreement with the outcome of the multivariate analysis of variance. The results indicated that these psychological measures were individually sensitive to differences among the three categories of subjects and, as a group, were capable of classifying children at a level far exceeding chance. It would appear that neuropsychological variables (brain-sensitive tests) may account for much of the uniqueness in many children with learning disabilities.


Racial and sexual bias in psychiatric diagnosis: psychiatrists and other mental health professionals compared by race, sex, and discipline.

In a study designed to test for sex- and race-related bias in psychiatric diagnosis, the responses of 173 mental health professionals to four hypothetical patient profiles were analyzed. Minimal racial bias was observed. In some instances, therapists appeared more likely to make judgments biased against patients who were of the same race and sex as themselves. The results support the contention that hysterical and antisocial personality disorders are sex-biased diagnoses. The race of the therapist strongly influenced diagnosis. It is argued that this finding reflects resistance of nonwhite therapists to a majority-group-dominated diagnostic theory. Professional discipline rarely affected diagnosis with the exception that psychiatrists were more prone to diagnose psychosis.


Self-inflicted eye injuries and self-inflicted blindness.

The case of a young man, suffering from schizophrenia, who injured his eyes with his hands and blinded himself, is described, along with his rehabilitation program. The classical and contemporary literature on self-inflicted blindness and self-inflicted eye injuries is reviewed and shows a wide range or psychiatric diagnoses and illustrates the inadequacy of attempting to apply oversimplified psychodynamic explanations. In contrast, the reaction to blindness appears to be relatively uniform, leading to the possibility of using established rehabilitation programs.


One-session cure of a case of speech anxiety with a 10-year follow-up.

This paper describes a television reporter suffering from verbal dyscontrol. The patient was treated successfully in one session using cognitive restructuring and Jacobson's technique of progressive muscle relaxation. This resulted in a diminution of anticipatory anxiety and relaxation of his laryngeal muscles, thus allowing him to speak more effectively. A 10-year follow-up revealed no relapse or symptom substitution, but instead, a marked improvement in his announcing ability resulting in steady promotions and success in other areas of his life. The author has had the unique opportunity to observe him on television for a period of 10 years, both prior to and following treatment.


Dividing "hysteria": a preliminary investigation of conversion disorder and psychalgia.

The longstanding diagnostic controversy over the concept of "hysteria" has taken on new significance with the advent and development of the third edition of the Diagnostic and Statistical Manual (DSM-III). The problem of defining hysteria is therefore discussed and re-examined. A retrospective study of cases diagnosed as conversion reaction or hysterical neurosis, conversion type was then completed and analyzed. These cases were redefined using DSM-III criteria and were analyzed using a number of demographic and clinical variables. In a comparison of those patients classified as having conversion and those classified as having psychalgia, no significant differences were found. Those patients under the diagnosis of conversion and those carrying the diagnosis psychalgia differed significantly from a control group of patients with random "neurotic" diagnosis on five variables: a) symptoms are defensive; b) symptoms are expressive; c) secondary gain; d) previous physical trauma; and e) previous conversion symptoms.


Single case study. Pseudodementia and mania.

This case report extends the discussion of pseudodementia into the area of manic behavior. An elderly patient whose manic symptoms are considered to be an early sign of an organic brain syndrome should be given timely repeat evaluations before this diagnosis is allowed to guide treatment. Our case presentation emphasized the paucity of the data base we have to diagnose cognitive and emotional disturbances of the elderly. It is difficult to identify the essential features of cognitive dysfunction associated with primary neuronal degeneration especially in the early stages of the disease. A careful differential diagnostic evaluation is important to eliminate variables such as affective disorders and underlying physical conditions as causes of confusion and cognitive dysfunction in the elderly patient.


Neurological, neuropsychological, and behavioral correlates of Klinefelter's syndrome.

Neuropsychological assessment is a rapidly expanding discipline combining skills from clinical psychology and neurology. Although neuropsychological correlates have been reported for a wide variety of clinical syndromes, little investigation of this kind has been done in the area of genetic abnormalities. The present case study concerned a child with a variant of Klinefelter's syndrome, genotype XXYY. Results of extensive neurological, psychological, and neuropsychological evaluations are presented and discussed. In addition, educational achievement and personality correlates of the syndrome are reported. Combined evaluation from all disciplines presented a picture of diffuse cortical impairment with slightly greater left hemisphere involvement, resulting in retardation. Previously proposed personality correlates of passivity, shyness, and dependency were also in evidence. On recommendation of the treatment team the child was placed in an  educable mentally retarded classroom and a 6-month follow-up showed him to be adjusting socially and functioning well in this setting. Although conclusions cannot be drawn from the study of a single case, data such as these may serve as a basis for future multidisciplinary approaches studying genetic abnormalities.


Briquet's syndrome in a man.

A case history is presented of a man who met the diagnostic criteria of Briquet's syndrome after a 7-year history of excessive use of psychiatric and medical health care services. Despite his having been seen by several psychiatrists, the diagnosis was made only following the use of the Schedule for Affective Disorders and Schizophrenia (SADS), a structured psychiatric interview, the results of which were applied to operationalized diagnostic criteria (Research Diagnostic Criteria [RDC]). This case demonstrates: 1) the fact that Briquet's Syndrome, commonly considered a female disorder, can occur in men; 2) the utility of structured interviews and defined diagnostic criteria in arriving at unexpected diagnoses; and 3) the importance of recognizing Briquet's Syndrome in order to avoid needless medical intervention for somatic complaints of psychological origins.


Some nonverbal aspects of depression and schizophrenia occurring during the interview.

Using remote control videotape recording of interviews and subsequent analysis of the record, eight measures of nonverbal behavior (principally facial) have been made in 12 schizophrenic and 13 depressive subjects shortly after admission to the hospital and again prior to discharge. They were matched with controls who were interviewed in a similar way. Additional videotape observations were made prior to the interview, when the patient was alone and subsequently when he was shown pictures designed to evoke emotional responses. It appears that some nonverbal behaviors can be used in the interview to differentiate between psychiatric patients and normals. These may also be useful as an index of clinical change since they revert toward the normal with clinical improvement. The nonverbal behaviors studied were more prominent in the interpersonal setting than when alone or when the subject was looking at pictorial stimuli. This implies that they may be elicited in response to another individual, either as a distortion of the ordinary nonverbal signaling system, or as physiological responses to a changed state of arousal induced by the interpersonal setting rather than as static characteristics of the syndrome.


Preconditions and consequences of transference interpretations. A clinical-quantitative investigation.

Our aim was to study the preconditions and consequences of transference interpretations by both quantitative and clinical methods. We selected the three specimen psychoanalytic treatments which had been studied most by clinical-quantitative research. For each patient the main data consisted of 16 interpretation contexts. The context of each interpretation included 250 patient words before and 250 patient words after the interpretation. Three judges independently rated these before and after segments for each of the 16 samples from each of the three patients. Judges tended to agree highly in rating these segments on nine variables. The before vs. after ratings showed that each patient had a different but individually typical response to the 16 interpretations, ranging from patient A who usually showed a negative response, to patient B who showed some positive response, to patient C who showed a very positive response. For each of these three patients there was a clear parallel between the positivity of the immediate response to interpretations and the outcome of treatment. Even though we have so far studied only three patients, the consistency of the results suggests that it would be worth testing in a larger group whether a sample of immediate responses to interpretations might predict the eventual outcome of the treatment. Patient factors seem central in explaining the bases for the different response of each of the three patients to transference interpretations. The Health-Sickness Rating Scale ratings showed that patient A and patient B were less healthy initially than patient C--healthier patients may be able to respond better to transference interpretations. Also, the analyses of the segments before the interpretation revealed that even before the interpretation there were differences in the three patients. These were consistent with their differing responses to interpretation; for example, patient A was rated as having less understanding than the other patients even before the interpretations. Another patient factor, the patient's readiness to experience a helping relationship, probably was significant also in explaining the differing response of the three patients to interpretations; they already differed in this experience by the third to fifth sessions, and these differences paralleled their response to interpretation.


Differences between self-reported and observed pleasure in depression and schizophrenia.

Observer ratings of positive affect and self-ratings of pleasurable experience were collected daily on six schizophrenic and five depressed inpatients during baseline medication-free periods ranging from 11 to 27 days. Schizophrenics were observed to display significantly higher degrees of positive affect than depressed patients, but they reported significantly lower degrees of experienced pleasure. Depressed patients, conversely, were observed to demonstrate significantly lower degrees of positive affect than schizophrenics, but they reported significantly higher degrees of experienced pleasure. These results have important implications for the further specification of mechanisms underlying abnormalities in pleasure associated with psychiatric disorders.


Racism as a response to change. The introduction of residents onto a psychiatry ward.

An outbreak of violence among inpatients coincident with the beginning of a residency training program is described. The phenomenon is viewed as an example of covert staff disagreement resulting in the scapegoating of black patients. Suggestions are made as to how to avoid the occurrence of similar phenomena through a process of re-education of ward staff.


Conversion reaction in an 82-year-old man.

Conversion reactions are considered rare in the elderly. The author offers a case report of an 82-year-old man with a conversion pain syndrome and points out that conversion reactions may occur at any age and among all personality styles.


Body opening symptoms and right-left sets.

Previous work demonstrated a relationship between the frequency with which an individual experiences stomach symptoms and the asymmetry he displays in perceiving and responding to the spatial dimension of up-down. This suggested that spatial asymmetries may mirror attitudes that have physiological and symptom consequences. The generality of this formulation was tested by examining the correlation between right-left perceptual asymmetries and various symptoms. It was demonstrated in both males and females, although more strongly in the former, that symptoms involving the body openings are significantly correlated with a left perceptual bias. A theory concerning the meaning of this relationship was offered and found to be supported in a male and also a female sample.


Anticoagulant abuse: a psychotic syndrome?

A case of surreptitious ingestion of oral anticoagulants is presented. The patient, a 31-year-old nurse, was followed for more than 3 years and underwent thorough psychological and psychiatric evaluation. Anticoagulant malingerers are by no means rare; however, little is known about the psychiatric disturbances in these patients. The tendency has been to regard these patients as having neurotic or personality disturbances. The data in the present case suggest that factitious hemorrhagic disease is caused by a psychotic disturbance. The results of psychiatric therapy are discussed.


Surreptitious use of warfarin.

The authors present the case of a 61-year-old woman who became increasingly sensitive to her warfarin. When she remained anticoagulated during a 2-month period off of warfarin a plasma analysis detected warfarin indicating she was taking the anticoagulant surreptitiously. This patient demonstrated features of factitious illness including a background of unsatisfactory childhood relationships, average intelligence, a lack of psychosis, and no obvious secondary gain. Surreptitious use of anticoagulants should be considered in all cases of unexplained hemorrhagic symptoms with low prothrombin activity.


The effects of response bias on sex differences in a psychiatric population.

A sample of 58 male and 84 female new admissions to a psychiatric facility was interviewed to identify sex differences in personal and social functioning. Female subjects were found to score significantly higher on intrapsychic distress scales while male subjects scored higher on scales measuring antisocial behavior. Using analysis of covariance, keeping the L- or Lie scale of the MMPI constant, all measures which had previously shown significant sex differences now became nonsignificant. This finding suggests that reported sex differences may be accounted for by response bias.


Models for metal-sulfur coordination in copper proteins.

The oxidation state of copper in several model compounds containing copper coordinated to sulfur, some of which are suggested model compounds for naturally occurring Cu-S chromophores, was determined employing x-ray photoelectron spectrometry. Copper was found to be present in a 3d10 state, which is characteristic for Cu(I). An initial photoreduction is excluded, as Cu(ethylenediamine)2 (SCN)2, in which a Cu-S bond is also present, was found to contain Cu(II) (3d9). As was the case with native parsley plastocyanin, the model compounds reacted effectively with superoxide anion radicals. We suggest that the electrons of the metal-sulfur chromophore in blue copper proteins are delocalized and that an equilibrium: RS--Cu(II) in equilibrium or formed from RS.Cu(I) exists.


Mobilization of iron from specifically labeled reticulocyte ghosts.

Specifically labeled 59Fe ghosts have been prepared by incubation of whole reticulocytes with 59Fe3+-transferrin-CO3(2)-- followed by washing and ghost isolation. The binding of 59Fe by the membrane fraction is quite stable over a wide range of conditions, but iron mobilization occurs on incubation with chelating agents or cell lysate. The time course of 59Fe mobilization by unlabeled reticulocyte lysate exhibits five apparently zero-order phases. The rate of iron mobilization is linearly dependent on the concentration of 59Fe ghosts present in the incubation mixture. In contrast, the relative concentration of lysate appears to exhibit a saturation dependence with regard to membrane iron mobilization. Bathophenanthroline sulfonate follows a multiphasic time course of iron mobilization similar to that found with the lysate. Lysate from mature erythrocytes was found to mobilize iron with kinetics that are identical to reticulocyte lysate. The number and duration of the phases is independent of the mobilizing agent. The role of the membrane fraction in regulating the rate of iron release to cytosol was also investigated by the repetitive incubation of 59Fe ghosts with fresh lysate. The rate of 59Fe mobilization depended on the condition of the ghost with regard to prior 59Fe depletion. This publication emphasizes the active role of the membrane fraction in determining the rate at which iron will become available to the cytosol and the possibility that cytosol factors modulate the action of membrane bound components.


Cryptofluorescent analogs of cobalamin coenzymes: synthesis and characterization.

Upper-axial (beta-position) ligand analogs of the B12 coenzymes 5'-deoxy-5'-adenosylcob(III)alamin and methylcob(III)alamin have been synthesized by reaction of the 5'-chloro-5'-deoxy derivatives of fluorescent nucleosides (1,N6-ethenoadenosine, formycin, 2-amino-nebularine, and 2,6-diaminonebularine) and a fluorescent alkyl halide (dansylamidopropyl chloride) with cob(I)alamin. These analogs were nonfluorescent, but fluorescent products could be generated by photolysis or cyanolysis of the carbon-cobalt bonds. Under anaerobic and aerobic conditions, the major fluorescent photolysis products of 1,N6-ethenoadenosylcob(III)alamin were 1,N6-etheno-5',8-cyclic-5'-deoxyadenosine, and the 5'-aldehyde of 1,N6-ethenoadenosine, respectively. The cryptofluorescent property of these analogs was utilized to follow the kinetics of aerobic photolysis. First-order rate constants determined by this method were comparable to those obtained spectrophotometrically [via appearance of of aquacob(III)alamin]. Pseudo-first-order rate constants determined fluorometrically for the cyanolysis (at 25 degrees C) of 1,N6-ethenoadenosylcob(III)alamin, 2,6-diaminonebularinylcob(III)alamin, 2-aminonebularinylcob(III)alamin and formycinylcob(III)alamin were 5.8 X 10(-2), 2 X 10(-2), 1.8 X 10(-2), and 3 X 10(-5) min-1, respectively; values in good agreement were obtained spectrophotometrically (via appearance of dicyanocobalamin). Dansylamidopropylcob(III)alamin was stable in the presence of cyanide. The nucleoside alpha-ribazole is fluorescent in the free state but nonfluorescent when present as the lower axial (alpha-position) ligand in cobalamin coenzymes. Thus fluorescence of ligands in both the alpha- and beta-positions of cobalamins is quenched, probably as a result of intramolecular energy transfer between the ligands and the nonfluorescent corrinoid.


Early reactions of cadmium with Ehrlich cells.

Ehrlich ascites tumor cells accumulate cadmium against a concentration gradient in a bisphasic uptake process. There is little efflux of the metal from preloaded cells into a cadmium-free medium. Incorporation of 3H-thymidine into DNA is markedly inhibited by cadmium ion at 5-100 ng atoms of Cd/mg of cell protein, but uptake of the nucleoside label into cells is not depressed in this concentration range. Cell respiration is much less affected by cadmium ion despite the sensitivity of isolated mitochondria to the metal. Model experiments using several cadmium complexes with known conditional formation constants show that bovine heart mitochondria have strong affinity for cadmium ion. The contrast between this result and the resistance of cells to respiratory inhibition with cadmium ion is discussed to illustrate the difficulty in relating in vitro studies to the cell. The behavior of cadmium ion with the Ehrlich cell is compared with data for zinc ion to reveal similarities in inhibition of nucleoside metabolism and respiration but a sharp difference in transport properties.


Morphological and biochemical findings in jejunal biopsies from patients with multiple sclerosis.

Gluten withdrawal from the diet is occasionally used speculatively in the management of multiple sclerosis. To assess whether there might be any rational basis for such a measure we have undertaken morphological and biochemical studies of the jejunal mucosa in 14 patients with multiple sclerosis. All were found to have morphologically normal villi, and quantitative estimation of surface-to-volume ratios gave values which did not differ from control subjects. Intraepithelial lymphocyte counts were normal. Antigliadin antibody titres were not raised in any patient. Estimation of activity of the brush border disaccharidases (sucrase, lactase, and maltase (showed that the mean level of each enzyme did not differ significantly from control subjects. Analytical subcellular fractionation of the biopsies showed no changes in the distribution or activity of marker enzymes for the brush order, lysosomes, mitochondria, cytosol, peroxisomes, or endoplasmic reticulum. It is concluded that there are no gross morphological or biochemical abnormalities in the jejunal mucosa in patients with multiple sclerosis and, therefore, that the use of gluten-free diets cannot be justified on the assumption that these patients suffer from a coeliac-like lesion of the small intestine.


Subtle disturbances of vision after optic neuritis elicited by studying contrast sensitivity.

Eight patients with a subjective disorder of vision yet normal Snellen acuities after optic neuritis were shown to have an abnormal contrast sensitivity function in their affected eye. It appears that certain disorders of vision are associated with an abnormality of the contrast sensitivity function in spite of near normal visual acuity. Such an abnormality may affect pattern recognition without having an influence on Snellen acuity because of the high contrast of the latter and its predominant association with the higher spatial frequencies. Contrast sensitivity function is thus the only tool available to study those aspects of vision which have remained impervious to other subjective tests of visual function.


Intradural enterogenous cyst.

A 23 year old woman with an intradural extramedullary enterogenous cyst in the cervical region, unassociated with vertebral cleft, presented with two episodes of neurological disturbance at an interval of five years. Subtotal excision of the anteriorly placed cyst at C6 vertebral level was followed by rapid and complete recovery.


Radiation myelopathy.

Five cases of radiation myelopathy were found in a total of 10,000 cases given radiotherapy from 1968 to 1977. The clinical presentation and treatment details including the total dose, treatment volume, number of fractionations, overall time, and the RET value at the spinal cord were calculated and compared with other reports on this subject. The total number of fractionations ranged from 20 to 26 with an overall time of 32 days to 37 days. The dose received by four patients ranged from 1030 to 1900 RET, a little higher than the tolerance level of the spinal cord as compared to reported values. Two patients in this series had high blood pressure. The incidence of radiation myelopathy, already acceptably low, could possibly be reduced further by meticulous planning of radiation.


Sensory functions in chronic neuralgia.

Eleven patients with sustained neuralgia, in most cases after traumatic nerve lesion, were subjected to quantitative sensory testing with thermal and non-noxious mechanical stimuli. Measurements were made in the pain area and at a homologous site on the contralateral normal side. All patients were hypoaesthetic with raised thresholds for warm and cold or touch, or both. Thermal pain thresholds were also raised in some patients but lowered in others indicating hypersensitivity of the nociceptor system or dysaesthesia for thermal input. In six patients single mechanical stimuli produced a painful response above the touch detection threshold. Reaction time measurements indicated that this painful response to suprathreshold mechanical pulses was measured by magnitude estimation as a function of stimulus amplitude. The results were fitted by power functions, as in normal skin, but with steeper slopes on the abnormal side. Suprathreshold hyperaesthesia (recruitment) may exist in the presence of normal threshold functioning.


Nerve conduction, tactile sensibility, and the electromyogram after suture or compression of peripheral nerve: a longitudinal study in man.

In three patients sequential studies were performed of sensory and motor conduction after complete section and suture of the median nerve at the wrist and in one patient after partial section of the nerve. The sensory potential evoked by stimuli to digits III and I and recorded proximal to the suture line at the wrist appeared after a delay of three to four months, corresponding to a growth rate of 1.5-2.0 mm per day. From early in the course of regeneration the sensory potential was dispersed in 40 components. In the adult patient the cumulative amplitude increased for two years slowly and thereafter at a two times faster rate. Amplitude and tactile sensibility were normal after 40 months, but the sensory potential was still five times more dispersed than normal. The overall increase in the amplitude of the sensory potentials in children aged 10 and 12 years was three times faster than in adults. In the adults and in the children the maximum sensory conduction velocity was 10-25% of normal. It then increased at 3% per month during the first two years, and thereafter 10 times slower. Forty months after suture in the adults and 13-19 months after suture in the children the conduction velocity had reached 65-75% of normal. The pattern of discrete electrical activity during voluntary effort and the prolonged duration of motor unit potentials indicate persistent enlargement of the reinnervated motor units by peripheral sprouting. The sensory potential recovered five times faster after a compressive nerve lesion than after section and suture as seen in another patient with an affection of the ulnar nerve at the elbow. Normal tactile sensibility was attained 10 times faster than after section and suture. Maximum sensory and motor condution velocity recovered within one year from 60-70% to 80-90% of normal.


Dopamine receptors and sleep induction in man.

Sleep induction has been studied in humans after the administration of apomorphine, a direct stimulant of the central dopaminergic system. The drug induced sleep and vomiting in healthy volunteers while it had no significant effect on 10 Parkinsonism patients treated for a long period with L-dopa. Apomorphine given to a group of Parkinsonism patients not receiving any specific treatment, and with a lower degree of disease severity, induced vomiting and sleep with a pattern similar to that in healthy subjects. A relationship between the dopaminergic system and sleep induction is suggested.


Late components of motor unit potentials in central core disease.

Electromyographic studies in five patients suffering from central core disease are presented. A variable amount of late components of motor unit potentials were found in all of them, as others have found in Duchenne muscular dystrophy. This suggests the existence of collateral innervation of the resultant fragments of the muscular fibre splitting present in this disorder.


Blink reflexes in severe traumatic coma.

Blink reflexes were studied in 21 patients in coma after severe head injury. Our observations suggest that blink reflexes are a simple, objective, neurophysiological test to evaluate brainstem function. Correlations between these reflexes and the anatomoclinical stanges of coma and the Glasgow coma scale have been established. Presence of the early R1 component shows the integrity of at least a part of the pontine structures. The appearance of the late R2 component is correlated with a better chance of recovery from coma.


Ventriculitis from Acinetobacter calcoaceticus variant anitratus.

Ventriculitis from infection with Acinetobacter calcoaceticus variant anitratus occurred in an infant two weeks after surgical repair of a lumbosacral meningomyelocele and ventriculoperitoneal shunting. Recovery took place on replacing the shunt with an extraventricular deviation device and giving gentamicin and ampicillin intravenously.


Reading difficulty as a presenting symptom in Wilson's disease.

A case of Wilson's disease is reported in which the major symptom before treatment was a reading disability. This was caused by ocular dysmetria, and the abnormal eye movements were recorded by electronystagmography and optokinetic drum testing.


Clofibrate-induced muscular syndrome. Report of a case with clinical, electromyographic and pathologic observations.

In this report the clinical features of a case of clofibrate-induced muscular syndrome, as well as the electromyographic, histochemical, light- and electron-microscopic findings are described. The clinical features are similar to those of previously reported cases. Electromyography was consistent with a myopathy. Histochemical profile was normal. The myopathology included breakdown of contractile material, deranged mitochondria, dilated sarcoplasmic reticulum profiles, accumulation of membrane bound dense bodies, discontinuities in sarcolemma and thickening of capillary basement membrane. Macrophages invaded severely affected fibers.


Myotonia, potassium and taurine. A preliminary report.

The effect of taurine administration upon potassium-induced muscular hyperexcitability was studied in patients affected with dystrophic myotonia and in normal volunteers. Intra-arterial infusions of increasing concentrations of potassium chloride were given and venous potassium levels simultaneously monitored. Taurine prevented or remarkably reduced the electric signs of muscular hyperexcitability. Potassium chloride and taurine effects upon muscular excitability are discussed in terms of changes of membrane conductance, particularly for potassium ions.


The limitation of pulsatile flow through the aqueduct of Sylvius as a cause of hydrocephalus.

The concept is advanced that hydrocephalus results from limitation in the pulsatile flow of CSF downwards through the aqueduct of Sylvius during systole which is necessary to accommodate for the pulsatile pressure and volume increase that accompanies the propagation of the arterial pulse through the brain. Evidence is given to show that flow through the fixed human aqueduct is disturbed and not laminar. Further, with the pressures availalbe, the aqueduct is only just large enough to pass the quantity of fluid which must be vented extracranially during systole. Should the capacity of this systolic venting mechanism be exceeded, physical strain will cause cellular damage in the periventricular and periaqueductal regions which, if prolonged, will lead to tissue destruction and hydrocephalus. There appear to be two main causes for hydrocephalus resulting from this mechanism. Firstly, structural lesions, restricting the lumina of the CSF-venting pathways, especially the aqueduct, will reduce the volume of CSF that can flow through these pathways during systole. The hydrocephalic process will then be continuous and only limited when tissue destruction reduces the systolic volume expansion of the brain such that it can be accomodated by the restricted CSF venting pathways. Secondly, conditions which may increase the amount of the systolic volume expansion of the brain beyond the capacity of the CSF venting pathways. Raised mean intracranial pressure is the most important of these conditions. In such cases the hydrocephalus will be limited by the duration of the causal process and possibly also by the enlargement of the venting pathways, as a result of tissue destruction. This hypothesis also accounts for hydrocephalus resulting from obliteration of the cortical subarachnoid space, obstruction to the cranial venous drainage, deformities in the region of the foramen magnum and arterial encroachment upon the ventricular system.


A freeze-fracture study of fiber types in normal human muscle.

The sarcoplasmic reticulum (SR) and plasma membranes of Type 1 and Type 2 fibers of normal human muscle were examined by the freeze-fracture technique. Total particle counts in the SR appeared much lower than in other mammals and a packing density of about 1200 particles/micrometer 2 was found in both longitudinal and cisternal components of SR. There was no difference in particle density of Type 1 and Type 2 fibers. In freeze-fracture replicas of plasma membranes several fiber type differences were seen. The surface caveolae were uniformly distributed in Type 1 fibers whereas in Type 2 they were clustered preferentially at the I-band levels. Total density of intramembranous particles was greater in Type 1 fibers (347 +/- 68/micrometer 2 in P-face, 58 +/- 11/micrometer 2 in E face) than in Type 2 fibers (207 +/- 30/micrometer 2 in P-face, 80 +/- 9/micrometer 2 in E-face). There was a striking difference in respect to rectilinear arrays which were virtually absent in Type 1 fibers (0--2/micrometer 2) and numberous (up to 50--70/micrometer 2) in Type 2 fibers.


Virus-induced demyelination. Production by a viral temperature-sensitive mutant.

Infection of mice with a temperature-sensitive (ts) mutant of Chandipura virus (CV) ts472 CV, induced a slower disease than the respective parental virus and white matter lesions characterized by perivascular mononuclear infiltrates accompanied by primary demyelination. The pattern of these lesions was very similar to that in EAE, a prototypic autoimmune disease and in Theiler's virus infection in which an immunopathologic mechanism of myelin injury is strongly suggested. Results obtained in nude mice supported the possible immunopathological nature of myelin injury in ts472 CV infection. No inflammatory response was elicited in either grey or white matter. However, whereas grey matter presented extensive necrosis, no alterations were present in white matter. Such data suggest that whereas grey matter lesions are produced by direct viral cytolytic activity, white matter pathology is probably dependent on the host immune response for its development. The finding of additional models of virus-induced demyelination with a possible immunopathologic mechanism of myelin injury is significant as it suggests that this type of virus-induced myelin degeneration is not restricted to a single virus like Theiler's, but it may represent a more general mechanism of virus-induced demyelination.


Quantitative electromyography using automatic analysis. A comparative study with a fixed fraction of a subject's maximum effort and two levels of thresholds for analysis.

Quantitative electromyographic (QEMG) data recorded with two levels of threshold for the apparatus are compared. Using a fixed fraction of a subject's maximum effort the data are shown to be independent of sex, age and the strength of the muscles. The diagnostic yield of such a method is shown to be better with 50 muV threshold for analysis than with 100 muV, in cases of muscle disorders such as Duchenne muscular dystrophy and polymyositis. However, in cases of neurogenic lesions due to anterior horn cell disease the diagnostic yield remains the same with both thresholds.


Nasal encephalocoele. Treatment by trans-cranial operation.

Results are described of 86 intracranial operations for the repair of nasal encephalocoele children at the Lahore Neurosurgical Centre in the last 13 years. These midline lesions at the base of the anterior cranial fossa have been considered in the past to be inoperable and even when operable, unpleasantly difficult. The intracranial approach has made it possible to treat this condition satisfactorily with comparatively few complications. Attempts at extra-cranial repair have met little success as they do not take into account the basic embryology and anatomy of the condition and fail to tackle the sac at the patent foramen caecum, the neck of the sac. This paper describes the embryology, anatomy, basic pathology and clinical features of the condition with characteristic X-rays showing the patent foramen caecum and outlines the operative repair.


The failure of microglia in normal brain to exhibit mononuclear phagocyte markers.

The origin of brain macrophages or "reactive microglia" has been the subject of considerable controversy. The fundamental question is whether or not there is a morphologically and functionally distinct population of cells, called microglia, which are resident in normal brain and differentiate into macrophages in response to inflammatory stimuli. The present study was performed to determine if any cells in the normal brain have the common markers of mononuclear phagocytes; phagocytosis, IgGFc receptors or macrophage specific antigens. In studies of the newborn and the adult murine brain and adult human brain no cells were detected which had any of those markers, although the highly sensitive marker methods were capable of detecting mononuclear phagocytes in all other tissues where they are known to occur. The results suggest that microglia, if they exist as a distinct cell type, are unrelated to mononuclear phagocytes. Furthermore, they suggest, but do not prove, that all inflammatory macrophages are derived from hematogenous precursors.