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For many severely handicapped children requiring external trunk support there is probably no better solution than to provide custom moulded seating. This will improve the patient's posture, reduce the occurrence of pressure sores and facilitate such activities as feeding. However, if large numbers of patients are to be supplied with this type of equipment, it is important that it should be manufactured at the lowest cost compatible with an acceptable quality. These manufacturing problems have been studied in considerable detail and a production method using vacuum consolidation casting together with a modified vacuum forming process has been developed. This has made it possible to produce custom moulded seating efficiently with the minimum of capital equipment. Much attention has been paid to the final appearance of the article and this has been enhanced by the use of commercially available items for the supporting structure and for the finishing of edges, etc. It is suggested that other orthoses could be redesigned for production using an approach similar to that described in this paper.

A modification of the fluorescence-activated cell sorter (FACS) was used to rapidly and reliably study the clonal proliferation of single hemopoietic cells. Murine FDC-P1 and human cord blood progenitor cells were examined for their ability to proliferate from single cells in 96-well microtiter plates containing agar medium and appropriate stimuli. FACS-sorted FDC-P1 single cells formed colonies in 345 out of 558 wells (62%), which compared favorably with control cultures (53%) and micromanipulated single cells (55%). Similarly, the frequency and type of day-14 colonies arising from cord blood progenitor cells when sorted as single cells by the FACS compared favorably with those grown from micromanipulated single cells or in control cultures.

In vitro infection of murine fetal liver cells with a retrovirus containing v-raf and v-myc oncogenes has produced continuous lines of immature erythroid cells that are leukemogenic. These cells synthesized a factor that stimulated their growth in vitro before autonomous variants emerged. Approximately 1000 high-affinity erythropoietin receptors could be detected per cell, and the hormone induced terminal differentiation in these cells. The lines were generated at an extremely low frequency (approximately 1 in 10(7) cells), suggesting that the combination of raf and myc is insufficient to develop erythroid cell lines and that additional events are necessary for transformation.

Two-locus theory for recurrent selection for general combining ability in maize was developed. The theory featured: (a) recombination of the selfed progeny of selected parents; and (b) linkage disequilibrium in the initial gametic array. The theory indicated: (a) that initial linkage disequilibrium exerts a permanent influence upon selection progress; (b) that interposition of one or more generations of random mating before each cycle reduces the permanent effect in ensuing cycles; and (c) that random mating done before initiation of selection is more efficient in removing the influence of linkage disequilibrium on selection progress than random mating done between subsequent cycles.

Normal human bone marrow mononuclear cells were fractionated by differential adherence, immunomagnetic separation, and fluorescence-activated cell sorting (FACS). The resultant fractionated cells were cultured in semisolid medium to monitor the presence of BFU-E, Mix-CFC, and nonerythroid CFC. Two populations of cells were recovered on the basis of binding by the monoclonal antibody (MoAb) RFB-1. One of these populations contained BFU-E that were stimulated only by erythropoietin (Epo), whereas the second population contained BFU-E responsive to Epo, Epo and recombinant human granulocyte-macrophage colony-stimulating factor (rHGM-CSF), or Epo and human placental-conditioned medium (HPCM). Prior enrichment of clonogenic cells by removal of adherent and Leu-M3+ve, Leu-4+ve, Leu-7+ve, B1+ve, WEMG1+ve, and Glycophorin A+ve cells, followed by FACS fractionation on the basis of RFB-1 binding, consistently resulted in recoveries of BFU-E, Mix-CFC, and nonerythroid CFC of greater than 100% (up to 800%). These procedures also resulted in enrichment of up to 200-fold and frequencies of 1:6 for BFU-E, 1:5 for CFC, and 1:130 for Mix-CFC.

The addition of 200 pM monoiodinated human atrial natriuretic factor-(99-126) (125I-hANF) to cultured bovine aortic smooth muscle cells at 37 degrees C resulted in a rapid clearance from the medium (t1/2 approximately 7.5 min). Within 5 min, [125I]iodotyrosine126 (125I-Y), Arg125-[125I]iodotyrosine126 (125I-RY) and Phe124-Arg-[125]iodotyrosine126 (125I-FRY) appeared in the medium. The identities of these degradation products were confirmed by 1) retention time on high performance liquid chromatography (HPLC) relative to standards, 2) products generated by digestion with aminopeptidase M, and 3) the absence of the Met110. Preincubation of the cells with ammonium chloride or chloroquine resulted in a significant increase in the intracellular accumulation of radiolabel, indicative of endocytosis and rapid delivery of 125I-hANF to an acidic intracellular compartment (endosome and/or lysosome). Neither ammonium chloride, chloroquine, nor excess unlabeled hANF blocked the rapid appearance in the medium of 125I-RY or 125I-FRY. Bestatin inhibited the generation of 125I-RY, with a concomitant increase in 125I-FRY, suggesting that the 125I-RY is produced by aminopeptidase action on 125I-FRY. The endopeptidase 24.11 (enkephalinase) inhibitor, SCH 39370, did not inhibit the formation of 125I-FRY. These results provide evidence of a peptidase capable of specifically removing the COOH-terminal tripeptide from 125I-hANF. The COOH-terminal tripeptide, Phe124-Arg-Tyr126, was also isolated from cell digests of hANF by HPLC and its identity confirmed by amino acid analysis. Since it is generally believed that the COOH-terminal tripeptide is critical to many of atrial natriuretic factor-(99-126)'s bioactivities, this enzyme may be involved in the inactivation of atrial natriuretic factor-(99-126) in target tissues.

An 8 to 10-week-old female New Zealand white rabbit, Oryctolagus cuniculus, which exhibited clinical signs of anorexia, depression, and torticollis was found to have lymphosarcoma with lymphoblastic leukemia. The multiple visceral involvement with neoplastic lymphoid cells observed in this animal was similar to previously reprted cases of lymphosarcoma in the rabbit. An unusual finding was the occurrence of lymphoblastic leukemia since lymphosarcoma in the rabbit has previously been reported as aleukemic.

A prominent feature of the inflammatory cellular response in the peritoneal cavity of Mesocestoides corti-infected mice is a marked and sustained increase in the number of eosinophils. In intact mice, the total number of nucleated cells in the peritoneal cavity rises from less than 5 X 10(6) to more than 50 X 10(6) and, at certain time points, in excess of 50% of these cells are eosinophils. Peritoneal eosinophils are absent in infected hypothymic nude (nu/nu) mice of three genotypes, and eosinophils counts can be elevated in infected nude mice by injection of peripheral lymphoid cells or thymocytes. The peritoneal cells of M. corti-infected mice are a convenient starting cell population for eosinophil purification.

To study the effects of dysregulated granulocyte-macrophage colony stimulating factor (GM-CSF) production, a retroviral vector (MPZen) containing a GM-CSF cDNA has been used to infect murine bone marrow cells prior to their transplantation into lethally-irradiated recipients. Animals transplanted with 1 x 10(6) bone marrow cells 14 to 21 days after transplantation displayed shortness of breath, trembling to the touch, and dragging of the hind limbs. These animals were shown to have increased peripheral blood neutrophil counts (x 200), decreased marrow cellularity (but with increased neutrophil and macrophage frequency) and increased spleen cellularity (with up to a 40-fold increase in neutrophil, macrophage and eosinophil frequency). Examination of sections of tissues from infected mice showed massive infiltration of neutrophils and macrophages in muscle, lungs, liver, and variable infiltration of these cells in lymphoid tissues and the eye. Haemopoietic tissues produced high levels of GM-CSF (10(5) Units/10(6) cells) and the serum contained up to 5.5 x 10(5) Units of GM-CSF per ml.

Separation of IgD-bearing B lymphocytes from the spleens of 3-week-old or adult mice has been achieved using cellular affinity columns and an anti-delta allotype serum. The results demonstrate that the majority of cells capable of forming B lymphocyte colonies in agar are delta-positive although they lose detectable IgD upon stimulation. It is proposed that these cells are the descendants of IgD-negative cells found in the fetal liver and neonatal spleen.

The lung lesions produced by multiple short-term intratracheal instillations of saline solutions of sodium zirconium lactate (NaZL), zirconium-aluminum-glycine hydroxychloride complex (ZAG), and aluminum chlorhydrate (ACH) in hamsters were studied by light and electron microscopy. These solutions produced lesions beginning with exudative pneumonia followed by pneumonitis (interstitial pneumonia) and foreign body granulomas. Electron microscopic microprobe analysis demonstrated the metallic component of the instilled compounds in membrane-bound cytoplasmic inclusions of macrophages. The lesions produced by NaZL and ZAG were similar to those produced by ACH. These lesions were also similar to those in previous reports of aerosol exposure of animals to zirconium or aluminum, or to other unrelated compounds.

The hemopoietic activities present in medium conditioned by a murine bone marrow-derived adherent cell line (B.Ad) have been studied. B.Ad-conditioned medium stimulated neutrophil, neutrophil-macrophage, and macrophage colonies in agar cultures of bone marrow cells and 90% of this activity was neutralized by antimacrophage colony-stimulating factor (anti-M-CSF). The conditioned medium supported the generation and/or maintenance of spleen colony-forming units (CFU-S) in liquid cultures and synergized with multilineage colony-stimulating factor (Multi-CSF; IL-3) to stimulate colony formation by day-3 post-5-fluorouracil (FU)-treated bone marrow cells. When used as feeder layers, B.Ad cells stimulated erythroid colony-forming units (CFU-E) and markedly enhanced erythroid burst-forming units (BFU-E) stimulation more than did maximal Multi-CSF (IL-3) and Epo stimulation. No CFU-E- or BFU-E-stimulating activities were detected in medium conditioned by B.Ad cells. Similarly, B.Ad-conditioned medium was unable to stimulate Multi-CSF (IL-3) or granulocyte-macrophage (GM)-CSF-dependent cell lines. The data suggest that medium conditioned by this bone marrow-derived adherent cell line contains M-CSF and other factors not detectable as CSFs that either directly or by means of a synergistic mechanism are able to stimulate CFU-S and colony-forming cells (CFC).

Studies with murine hematopoietic cells have characterized three separate molecular species acting at some point on the erythropoietic lineage (GM-CSF, BPA, Epo). These studies have been performed mainly with adult tissues, and during the embryonic phase of murine development only macrophage colony-stimulating factor and an activity capable of stimulating CFU-E can be detected in yolk sac fluid. Multipotential or erythroid-committed progenitor cells (BFU-E) obtained from 9-day murine embryos produce only adult hemoglobins when stimulated with an adult source of BPA. Studies with human cord blood erythroid progenitor cells have failed to detect a human equivalent of murine BPA. Clone transfer experiments suggest that erythropoietin alone is required to stimulate human cord blood BFU-E. Experiments of similar design are required to determine the role of various hemopoietic regulatory factors in adult human erythropoiesis.

It is useful to know that household pets are not involved in the life cycles of some worms, for example, pinworms. Some worms require a household pet in their cycles: the dog and cat roundworms, heartworms, and the dog and cat hookworms, the larvae of which are responsible for cutaneous larva migrans. Strongyloides (threadworm) infestation is sometimes difficult to diagnose and may be traced directly to the family dog.

Spectral analysis methods have been used to examine the influence of shock absorbing inserts on heel strike transients in normal gait. The data were obtained from a piezoelectric accelerometer mounted on a custom moulded splint fitting around the malleoli which was found to eliminate unwanted resonances. The peak accelerations measured with this system were similar to those obtained in earlier studies. Examination of the gait of one subject in four different types of footwear showed that a reduction of rms acceleration could be achieved by the use of a shock absorbing insert. The efficiency of the insert was measured by its ability to reduce the rms acceleration in the 10–150 Hz band and to reduce the rms signal in the 50–150 Hz band as a proportion of the total. This second measure was defined as the ‘Shock Factor’.

High concentrations of haloperidol are seen in a psychiatric patient who ran from a health care facility into traffic. Haloperidol concentrations were found to be 1.2 mg/L in heart blood, 2.7 mg/L in brain, and 10.8 mg/L in liver. No other drugs were detected.

Previous investigations have shown that the teratocarcinoma line PCC3/A/1 is able to differentiate in vitro to produce red blood cells of the primitive hemopoietic cell population of the mouse embryo. The present paper demonstrates the presence in the same cultures of multipotential cells capable of giving rise to colonies containing erythrocytes, macrophages, and megakaryocytes when stimulated by pokeweed-mitogen spleen-cell conditioned medium.

The ontogeny of IgD was examined in neonatal to adult mice by immunofluorescence. The first delta-positive cells appeared in the spleen at about 3 days of age, while lymph nodes from 4 to 5-day-old mice already contained 10--20% delta-positive B cells. In order to study the function of IgD, we developed a system in which the appearance of delta-positive cells was suppressed by treatment of mice from birth with an anti-delta allotype serum. Immunofluorescence studies showed that very few delta-positive cells could be found in the spleen and lymph nodes of such suppressed mice, and also that the percentage of mu-positive cells was reduced by about 50%. The recovery from suppression was rapid, indicating that potential delta-positive cells were modulated rather than killed. Studies of the immune response of suppressed mice in vitro and in vivo showed that suppression had little effect on the IgM response but caused a definite reduction in the IgG response.

Pseudobinary alloys of the form Nb3AxB1 − x (where A and B represent the nontransition elements Al, Ga, Ge, and Si) were prepared and studied using X-ray diffraction. An A15 phase of Nb3Si and Al5 ternary derivatives were identified. The variation of the superconducting transition temperature T c and the Al5 lattice parameter a 0 as a function of composition was measured.

A naturally occurring inducer of terminal differentiation in a murine myelomonocytic leukemia cell line (WEHI-3B) was purified to apparent homogeneity from medium conditioned by lungs from mice injected with bacterial endotoxin. The factor was purified over 400,000-fold by sequential fractionation using salting out chromatography, chromatography on phenyl-Sepharose, gel filtration on Bio-Gel P-60 in 1 M acetic acid, reverse-phase high performance liquid chromatography on a phenyl-silica column, and high performance liquid chromatography on a gel filtration column. During the first two steps, the differentiation-inducing factor was separated completely from a known proliferative regulator for normal myeloid cells, granulocyte-macrophage colony-stimulating factor, but it co-purified through all remaining steps with a distinct granulocyte-specific colony-stimulating factor. The purified factor showed a single protein band of Mr = 24,000-25,000 on sodium dodecyl sulfate-polyacrylamide gels coincident with both differentiation-inducing and granulocyte colony-stimulating activity. The granulocyte-specific colony-stimulating factor was active on WEHI-3B cells and normal granulocytic progenitor cells in vitro at the same half-maximally active concentration of 3 X 10(-12) M.

This report examines various computational approaches for projectile impact onto concrete targets. Included are two- and three-dimensional computations performed with both the Epic-2 and Epic-3 codes. Various techniques, such as tunneling, eroding, and NABOR nodes, are used to compare results and demonstrate capabilities. Results are presented for normal, oblique, and yawed impact. This report also documents the NABOR algorithms for axisymmetric and three-dimensional geometry. These NABOR algorithms allow for variable nodal connectivity and are well suited for projectile-concrete impact problems.

A simple two-step procedure has been developed for the production of human urinary erythropoietin suitable for tissue culture use. Lyophilized human urinary protein was fractionated by phenyl-Sepharose chromatography, the erythropoietin binding in 2 M lithium chloride and being eluted by an ascending linear gradient to 6 M guanidine hydrochloride. The erythropoietin was further purified by ethanol (75% vol/vol) precipitation. This two-step procedure resulted in a 25-fold purification of erythropoietin with a 50% recovery of the starting activity. The erythropoietin preparation was suitable for use in murine or human cultures, being free of protease activity, inhibitory factors, colony-stimulating factors, and erythroid-enhancing activities.

Murine embryonic and fetal yolk-sacs, peripheral blood, and livers were assayed for hemopoietic multipotential and progenitor cell content between days 6 and 13 of gestation. Multipotential cells (Mix-CFC), erythroid-committed progenitor cells (BFU-E), and nonerythroid progenitor cells (predominantly GM-CFC) were assayed by their ability to form hemopoietic colonies in vitro when stimulated by pokeweed-mitogen-stimulated spleen-cell-conditioned media (as a source of Multi-CSF) and either human or murine erythropoietin. Late erythroid progenitor cells (CFU-E) were stimulated to form colonies by erythropoietin. Mix-CFC, BFU-E, and nonerythroid cells were first detected on day 8 in yolk-sacs, day 9 in peripheral blood, and day 11 in liver. Maximum absolute numbers of yolk-sac Mix-CFC (182), BFU-E (331), and non-erythroid CFC (1358) occurred at 11 days of gestation. The maximum frequency of peripheral blood mix-CFC (24/10(5) cells) and BFU-E (55/10(5) cells) occurred at ten days of gestation. The absolute numbers of hepatic Mix-CFC, BFU-E, nonerythroid CFC, and CFU-E increased exponentially from 11 to 13 days' gestation. CFU-E were first detected at nine days in peripheral blood, at ten days in yolk-sac, and 11 days in liver and at all ages were equally responsive to erythropoietin. The maximum frequency (151/10(5) cells) of CFU-E in the peripheral blood and the maximum number per yolk-sac (1699) both occurred on day 11 of gestation. In confirmation of previous studies, yolk-sac fluid was found to contain a macrophage colony-stimulating activity. In addition, an activity capable of stimulating fetal liver CFU-E was also detected in yolk-sac fluid. However, no activity (Multi-CSF) capable of stimulating Mix-CFC or BFU-E was detected in either yolk-sac fluid or fetal plasma.

Cells from CBA fetal mouse liver formed pure or mixed erythroid colonies in semisolid agarculture after stimulation by medium conditioned by pokeweed mitogen-stimulated mouse spleen cells. In general shape, the erythroid colonies resembled typical 7-day single or multiple (burst) colonies. However one-third to one-half contained, in addition to erythroid cells, macrophages and neutrophils and, less commonly, megakaryocytes or eosinophils. Culture of micro manipulated single colony-forming cells showed these erythroid colonies to be clones. Colony-forming cells declined in frequency with advancing fetal age, but low numbers were detectable in adult bone marrow. Assays of spleen conditioned medium in polycythemic mice failed to detect erythropoietin; the cloning system may detect a fetal type of erythropoietin-independent, erythropoietic cell since few were detected in adult marrow.

Globoid cell leukodystrophy was diagnosed in a purebred Beagle bitch. Clinical signs and histopathologic and ultrastructural features were consistent with those reported in globoid cell leukodystrophy in man, cat, and other breeds of dogs. The occurrence of the disorder in 2 clinically affected females from a related litter and a familial history of inbreeding support the existence of a familial pattern.

Colonies containing blast cells (greater than 95%) have been characterized in 14-day cultures of normal murine bone marrow or spleen cells, stimulated by an adherent bone marrow cell line, B.Ad. These blast cell colonies occurred at a frequency of 1-2 per 2.5 X 10(4) bone marrow or 2.5 X 10(5) spleen cells and contained from 0.7 to 14.7 X 10(4) cells. Assay of individual blast cell colonies showed that they contained day 8 and day 13 colony-forming units-spleen (CFU-S) and from 11 to 10,434 in vitro CFC. Chromosomally marked blast colony cells were transplanted into lethally irradiated recipients and shown to produce both myeloid and lymphoid progeny in the recipients' bone marrow, spleen, mesenteric lymph node, and thymus.

The possible role of an antibody-dependent cellular cytotoxicity (ADCC)-type mechanism in the passive serum therapy of Friend leukemia virus (FLV)-induced erythroleukemia has been investigated by determining whether successful serum protection requires an intact Fc portion on the administered antibody. F(ab')2 fragments of IgG extracted from chimpanzee anti-FLV and goat anti-FLV gp71 antisera were prepared and compared with whole serum and uncleaved IgG for their capacity to protect DBA/2 mice against challenge with leukemogenic dose of FLV. Despite demonstrating in vitro virus neutralizing activity equivalent to that seen with antiviral serum or IgG, the virus-specific F(ab')2 preparations were devoid of protective activity. Given that passively administered F(ab')2 of goat origin have been reported to persist at stable levels in the mouse circulation, the failure of these F(ab')2 preparations to protect against virus challenge cannot be ascribed to rapid clearance from the treated animals. These results indicate that the passive serum therapy of FLV-induced disease is Fc dependent, consistent with the involvement of an ADCC-type mechanism, as well as confirming the previous suggestion that virus neutralization does not represent the sole mechanism of serum protection in this system.

Ventilation minute volume, tidal volume and cardiac frequency during submaximal exercise have been measured in healthy young soldier volunteers exposed to O-chlorobenzylidene malononitrile (CS) and ammonia gas in concentrations respectively of 0.16 to 4.4 mg.m(-3) and 50 to 344 mg.m(-3). The response of ventilation minute volume to the two gases is apparently similar; both gases cause a reduction of, on average 6%. With low doses this reflects a diminution in respiratory frequency whereas with higher doses it is due to a reduction in tidal volume which is accompanied by tachypnoea. The findings may result from stimulation successively of receptors in the larynx and of irritant receptors in the large airways of the lung. The pain which is a feature of exposure to CS but not to ammonia is due to stimulation of other so far unidentified receptors. Neither gas has a direct effect upon the exercise cardiac frequency.

Amongst 288 healthy male workers in heavy industry the radiographic heart volume was related to the fat-free mass and the percentage body fat which between them explained 27% of the variance. Exercise was performed on a treadmill using a belt speed of 80 m.min-1 (3 mph) and an incline which was increased progressively to 14% when the oxygen uptake was on average 61% of the maximum for these subjects. The exercise cardiac output was related to the uptake of oxygen, the fat-free mass and the ambient temperature; these factors accounted for 52% of the variance. The exercise stroke volume was related to the heart volume, the fat-free mass, the thigh muscle width, the ambient temperature, the Harvard Pack Index and other measurements which between them accounted for 42% of the variance. The exercise cardiac frequency was correlated negatively with the heart volume, the fat-free mass, the age and the Harvard Pack Index. The variates between them described 41% of the variance. The findings provide reference values for heart volume, stroke volume and exercise cardiac frequency in similar subjects.

The rates of hydrolysis, oxidation and thermal degradation were studied as functions of temperature, relative humidity and film thickness. The rate of hydrolysis was found to be very much faster than the rates of the other two reactions. A relation between extent of chemical degradation and physical degradation has been established and the effect of both on electrical properties is shown. Using these data one may estimate the time required for the polymer to reach a given degree of degradation at any chosen temperature and relative humidity.

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Data published on polytetrafluoroethylene, such as the government-supported EPIC Report S-3,1 probably do not reflect the recent advances in techniques for measuring dielectric properties. Our work was initiated in an attempt to provide dielectric data representative of the measurement accuracy available today.

The actions of 17 beta-estradiol (E2) and protein kinase C (PKC) appear to converge in the regulation of expression of certain growth modulatory genes, such as the growth factor amphiregulin (AR). AR is known to modulate cell growth by binding to the epidermal growth factor receptor. In the current report we established the mechanisms of the PKC-activating phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA) and the steroid hormone E2 on the induction of AR expression in human breast carcinoma cell lines. TPA (100 nM) and E2 (1 nM) induce AR messenger RNA (mRNA) expression by 6- to 8-fold and 3- to 6-fold, respectively, in a time- and dose-dependent manner. In addition, immunoreactive AR protein is induced by both TPA and E2 by 6- to 8-fold and 2- to 4-fold, respectively. The PKC-modulating drugs, bryostatin and H-7, and antiestrogens (ICI 164,384 and 4-hydroxytamoxifen) interfere with AR induction by TPA and estrogen, respectively. The effects of TPA and E2 on the induction of AR mRNA were both closely associated with enhanced transcription of the AR gene. However, TPA had an additional effect at the posttranscriptional level by stabilizing the AR mRNA. The protein synthesis inhibitor, cycloheximide, prevented AR induction by TPA, suggesting that a component of the TPA induction of AR is indirect and dependent upon protein synthesis. Conversely, the E2 induction of AR transcription was found to be a direct response, independent of protein synthesis. The results presented herein thus demonstrate that TPA and E2 are able to stimulate AR gene transcription by two separate mechanisms.