Showing papers by "Oregon Health & Science University published in 1989"
Journal Article•
TL;DR: Using the polymerase chain reaction to amplify a (TG)n microsatellite in the human cardiac actin gene, 12 different allelic fragments in 37 unrelated individuals were detected, 32 of whom were heterozygous and Codominant Mendelian inheritance of fragments was observed in three families with a total of 24 children.
Abstract: The human genome contains approximately 50,000 copies of an interspersed repeat with the sequence (dT-dG)n, where n = approximately 10-60. In humans, (TG)n repeats have been found in several sequenced regions. Since minisatellite regions with larger repeat elements often display extensive length polymorphisms, we suspected that (TG)n repeats ("microsatellites") might also be polymorphic. Using the polymerase chain reaction to amplify a (TG)n microsatellite in the human cardiac actin gene, we detected 12 different allelic fragments in 37 unrelated individuals, 32 of whom were heterozygous. Codominant Mendelian inheritance of fragments was observed in three families with a total of 24 children. Because of the widespread distribution of (TG)n microsatellites, polymorphisms of this type may be generally abundant and present in regions where minisatellites are rare, making such microsatellite loci very useful for linkage studies in humans.
1,982 citations
TL;DR: The first recordings of currents through single ion channels activated by 5-HT3 receptors are reported, in excised membrane patches from neurons of the guinea pig submucous plexus, implying a role for 5- HT, and perhaps other amines, as a 'fast' synaptic transmitter.
Abstract: The neurohormone 5-hydroxytryptamine (5HT or serotonin) exerts its effects by binding to several distinct receptors. One of these is the M-receptor of Gaddum and Picarelli, now called the 5-HT3 receptor, through which 5-HT acts to excite enteric neurons. Ligand-binding and functional studies have shown that the 5-HT3 receptor is widely distributed in peripheral and central nervous tissue and evidence suggests that the receptor might incorporate an ion channel permeable to cations. We now report the first recordings of currents through single ion channels activated by 5-HT3 receptors, in excised (outside-out) membrane patches from neurons of the guinea pig submucous plexus. Whereas application of acetylcholine activated predominantly a 40-pS channel, 5-HT caused unitary currents apparently through two channels of conductances of 15 and 9 pS, which were reversibly blocked by antagonists of the 5-HT3 receptor. Receptors for amine neurotransmitters, including 5-HT1 and 5-HT2, have previously been thought to transduce their effects through GTP-binding proteins: the direct demonstration that 5-HT3 receptors are ligand-gated ion channels implies a role for 5-HT, and perhaps other amines, as a 'fast' synaptic transmitter.
658 citations
TL;DR: This is the first report demonstrating the use of a synthetic T CR V-region peptide to induce specific regulatory immunity and has important implications for the regulation of human disease characterized by common TCR V-gene usage.
Abstract: T CELLS expressing the αβ T-cell receptor (TCR) for antigen can elicit anti-idiotypic antibodies specific for the TCR that regulate T-cell function1–4. Defined sequences of the TCR, however, have not been used to elicit specific antibodies and the role of cellular immunity directed against TCR determinants has not been studied. We immunized Lewis rats with a synthetic peptide representing a hypervariable region of the TCR β8 molecule. Subsequent induction of experimental autoimmune encephalomyelitis, a paralytic disease of the central nervous system mediated primarily by Vβ8+ T cells specific for myelin basic protein5,6 was prevented. T cells specific for the TCR Vβ8 peptide conferred passive protection against the disease to naive rats, apparently by shifting the predominant T-cell response away from the major encephalitogenic epitope of basic protein. This is the first report demonstrating the use of a synthetic TCR V-region peptide to induce specific regulatory immunity and has important implications for the regulation of human disease characterized by common TCR V-gene usage.
605 citations
TL;DR: Maternal inheritance of the deleted chromosome 15 was demonstrated in the AS patients by restriction fragment length polymorphisms (RFLPs) and the molecular deletions between AS and those previously reported for PWS did not appear to differ.
Abstract: Many Prader-Willi syndrome (PWS) and Angelman syndrome (AS) patients have a cytogenetic deletion of 15q11q13. While AS and PWS share a similar cytogenetic anomaly, they have very different clinical phenotypes. DNAs from 4 AS patients were examined using 5 chromosome 15q11q13-specific cloned DNA segments. With the present level of resolution, the molecular deletions between AS and those previously reported for PWS did not appear to differ. However, in contrast to the paternal inheritance of the deleted chromosome 15 observed in the majority of PWS patients, maternal inheritance of the deleted chromosome 15 was demonstrated in the AS patients by restriction fragment length polymorphisms (RFLPs).
544 citations
TL;DR: Findings indicate that NASH is, in general, a clinically mild and biologically low-grade condition, but with the potential to progress and evolve into cirrhosis in some patients, although the factors promoting progression are unclear.
536 citations
TL;DR: In this paper, a human D2 dopamine receptor was sequenced from a pituitary cDNA library and sequenced with the deduced protein sequence is 96% identical with that of the cloned rat receptor with one major difference: the human receptor contains an additional 29 amino acids in its putative third cytoplasmic loop.
Abstract: A clone encoding a human D2 dopamine receptor was isolated from a pituitary cDNA library and sequenced. The deduced protein sequence is 96% identical with that of the cloned rat receptor with one major difference: the human receptor contains an additional 29 amino acids in its putative third cytoplasmic loop. Southern blotting demonstrated the presence of only one human D2 receptor gene. Two overlapping phage containing the gene were isolated and characterized. DNA sequence analysis of these clones showed that the coding sequence is interrupted by six introns and that the additional amino acids present in the human pituitary receptor are encoded by a single exon of 87 base pairs. The involvement of this sequence in alternative splicing and its biological significance are discussed.
475 citations
Journal Article•
TL;DR: A search for RFLPs associated with D2DR identified a frequent two-allele TaqI RFLP that binds to the q22-q23 junction of chromosome 11 and is associated with antipsychotic drugs.
Abstract: Human dopaminergic neurons are involved in the control of hormone secretion, voluntary movement, and emotional behavior. Mediating these effects are the dopamine D1 and D2 receptors. These macromolecules belong to a large family of related sequences known as the G protein-coupled receptors. The D2 receptors have been of special interest because they bind, with high affinity and specificity, many of the commonly prescribed antipsychotic drugs. We previously isolated a full-length cDNA clone of the rat D2 receptor. When a chromosome mapping panel was probed with the rat D2 receptor cDNA a 15-kb EcoRI restriction fragment was identified and localized to human chromosome 11. The rat cDNA was also used to clone a human genomic fragment, lambda hD2G1, which contains the last coding exon of the D2 receptor gene (DRD2) and 16.5 kb of 3' flanking sequence. Hybridization of lambda hD2G1 to a chromosome 11 regional mapping panel localized DRD2 to 11q. In situ hybridization of lambda hD2G1 to metaphase chromosomes refined this assignment to the q22-q23 junction of chromosome 11. A search for RFLPs associated with D2DR identified a frequent two-allele TaqI RFLP.
436 citations
TL;DR: The properties of these 2 cell types broadly correspond with those described by electrophysiological studies in vivo, in which case the majority, or principal, cells are believed to be dopaminergic.
Abstract: Intracellular recordings were made from 475 rat substantia nigra zona compacta neurons in vitro. The region from which recordings were made was rich in catecholamine fluorescence. Two groups of neuron, termed principal neurons (95% of the total) and secondary neurons (5% of the total) were clearly distinguishable according to one or more of the following 4 electrophysiological properties. Secondary neurons (23 cells) (1) fired spontaneous action potentials at frequencies greater than 10 Hz, or were quiescent (30%); (2) had action potentials less than 1 msec in duration; (3) did not show time-dependent inward rectification with step hyperpolarization; and (4) had slope conductances of about 4 nS (between -75 and -90 mV). In contrast, principal neurons (1) fired spontaneous action potentials in the range 1–8 Hz, or were quiescent (33%); (2) had action potentials greater than 1 msec in duration; (3) showed pronounced time-dependent inward rectification; and (4) had steady-state membrane slope conductances of around 22 nS (between -75 and -90 mV). Secondary cells were not affected by dopamine but were hyperpolarized by baclofen, GABA, and the mu opioid receptor agonist Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO). On the other hand, dopamine and baclofen inhibited firing and/or hyperpolarized all principal cells tested, but mu or delta opioid receptor agonists had no effect. The properties of these 2 cell types broadly correspond with those described by electrophysiological studies in vivo, in which case the majority, or principal, cells are believed to be dopaminergic.(ABSTRACT TRUNCATED AT 250 WORDS)
420 citations
TL;DR: A large number of patients with known CMV infections, especially recipients of bone marrow and solid-organ transplants and those with the a...
Abstract: CYTOMEGALOVIRUS (CMV) infections are a major cause of morbidity and mortality among immunocompromised patients, especially recipients of bone marrow and solid-organ transplants and those with the a...
406 citations
TL;DR: By measuring the onset of melatonin production, a clearly demarcated event, the authors can reliably assess circadian phase position, provided blood is sampled under dim light (the dim light melatonin onset, or DLMO), which has been useful in assessing the phase-shifting properties of bright light and in phase typing patients with chronobiologic disorders, such as winter depression.
Abstract: Masking is known to affect a variety of circadian rhythms, making it difficult to use them as reliable markers of circadian phase position. Melatonin may be unique in that it appears to be masked only by (bright) light. Sleep and activity do not appear to influence the melatonin rhythm. By measuring the onset of melatonin production, a clearly demarcated event, we can reliably assess circadian phase position, provided blood is sampled under dim light (the dim light melatonin onset, or DLMO). The DLMO has been useful in assessing the phase-shifting properties of bright light and in phase typing patients with chronobiologic disorders, such as winter depression.
387 citations
TL;DR: Reliability and validity of the Flanagan Quality of Life Scale (QOLS) were tested in four chronic illness groups and Appropriate validity coefficients indicated both convergent and discriminant construct validity.
Abstract: Reliability and validity of the Flanagan Quality of Life Scale (QOLS) were tested in four chronic illness groups. Open-ended questions and four instruments, the QOLS, Duke-UNC Health Profile (DUHP), Life Satisfaction Index (LSI-Z), and either the Arthritis Impact Measurement Scales (AIMS) or the Ostomy Adjustment Scale (OAS) were administered by telephone interview and mailed questionnaires to 227 adults three times over 6 weeks. Subjects generated verbal responses that substantiated the content validity of the QOLS. Stability reliability estimates for all instruments ranged from .53 to .90. Cronbach's alpha coefficients averaged .87 for the QOLS. Appropriate validity coefficients indicated both convergent and discriminant construct validity.
TL;DR: Responses to ACh and nicotine resemble those previously described on autonomic ganglion cells and may contribute to the positive reinforcement associated with nicotine consumption in rat brain slices.
Abstract: 1. Intracellular recordings were made from presumed dopamine-containing neurones in the ventral tegmental area (VTA) in rat brain slices. 2. Nicotine (10-100 microM) and acetylcholine (ACh) depolarized the neurones. The depolarization caused by ACh was typically biphasic; both components were increased by neostigmine (0.1-10 microM), but only the slower component was blocked by scopolamine (1-10 microM). 3. The nicotinic action of ACh, studied in the presence of neostigmine and scopolamine, persisted in the presence of tetrodotoxin (1 microM) and cobalt (2-5 mM). 4. ACh or carbachol (30 microM) caused inward currents in neurones voltage-clamped near the resting potential. These currents reversed polarity at around -4 mV, were blocked by hexamethonium (1-100 microM) in a voltage-dependent manner, and showed desensitization with prolonged or repeated agonist applications. 5. Depolarizations caused by ACh and carbachol were reduced in slices pretreated with kappa-bungarotoxin, but were not changed by alpha-bungarotoxin. 6. These responses to ACh and nicotine resemble those previously described on autonomic ganglion cells. The direct action on VTA neurones may contribute to the positive reinforcement associated with nicotine consumption.
TL;DR: It would be trite indeed to say much to this audience of the contributions to pharmacology made by Sir John Gaddum, but his quantitative approaches to the study of drug antagonism have found their way into most textbooks of pharmacology.
Abstract: It would be trite indeed to say much to this audience of the contributions to pharmacology made by Sir John Gaddum. His quantitative approaches to the study of drug antagonism have found their way into most textbooks of pharmacology. I dare say that, if asked to define that aspect of the subject which is uniquely 'pharmacology'-a task of increasing difficulty in these interdisciplinary days-many Society members would think first of those quantitative methods for studying drug-receptor interactions spawned by A.J. Clark, tested with antagonists by John Gaddum, and much popularized by Heinz Schild (Clark, 1933; Gaddum, 1937; 1957; Schild, 1949). I thank the Trustees for providing me with the opportunity to add my own small tribute to the memory of John Gaddum's work; this is particularly so because-as you will see-my own research has been much influenced by his contributions. John Gaddum worked mostly with peripheral tissues. This was convenient because the tissues were readily accessible, easy to maintain in vitro, and in those days devites could be made to measure the appropriate response, such as contraction, relaxation or secretion; furthermore, it was generally not important to distinguish the drug effects on the individual cells within the syncytium. The first efforts to classify receptors on nerves were also made at their terminations in the periphery, following on from the well-known observations of Lindor Brown and John Gillespie (1957). That field, the study of autonomic presynaptic receptors, has matured and has led to novel therapies. But in the ganglia of the autonomic nervous system and in the central nervous system, the individual nerve cell is the functional unit, and information about drug receptors on nerve cells can best be obtained by recording from single cells. Conversely, the demonstration and characterization of drug receptors on nerve cells can itself be used as a way of classifying the cells, particularly when taken in concert with other information regarding the ion channels expressed, the transmitters synthesized and the targets to which the cells project.
TL;DR: Blue cone monochromacy is a rare X-linked disorder of color vision characterized by the absence of both red and green cone sensitivities; in 12 of 12 families carrying this trait, alterations are observed in the red andGreen visual pigment gene cluster.
Abstract: Blue cone monochromacy is a rare X-linked disorder of color vision characterized by the absence of both red and green cone sensitivities. In 12 of 12 families carrying this trait, alterations are observed in the red and green visual pigment gene cluster. The alterations fall into two classes. One class arose from the wild type by a two-step pathway consisting of unequal homologous recombination and point mutation. The second class arose by nonhomologous deletion of genomic DNA adjacent to the red and green pigment gene cluster. These deletions define a 579-base pair region that is located 4 kilobases upstream of the red pigment gene and 43 kilobases upstream of the nearest green pigment gene; this 579-base pair region is essential for the activity of both pigment genes.
TL;DR: This dystonia gene (ITD1) shows tight linkage with the gene encoding gelsolin, an actin binding protein, and appears by multipoint linkage analysis to lie in the q32-q34 region of chromosome 9 between ABO and D9S26, a region that also contains the locus for dopamine-beta-hydroxylase.
TL;DR: Twenty-seven Cambodian young people, who were severely traumatized at ages 8 to 12, were followed up 3 years after an original study, and it was shown that post-traumatic stress disorders (PTSD) were still highly prevalent.
Abstract: Twenty-seven Cambodian young people, who were severely traumatized at ages 8 to 12, were followed up 3 years after an original study. A structured interview and self-rating scales showed that post-traumatic stress disorders (PTSD) were still highly prevalent (48%). Depression existed in 41%. Those with PTSD differed significantly from those without PTSD on the Global Adjustment Scale, the Social Adjustment Scale, the Beck Depression Inventory, and the Impact of Event Scale. Eight subjects had PTSD at both interviews, while 11 had none at either time. Eight showed a variable course. Avoidance behavior was highly prevalent, even among those without PTSD diagnosis. Although functioning relatively well, these youths continued to show symptoms related to their trauma of 8 to 12 years before.
TL;DR: In patients with unexplained cerebral ischemia, establishing the presence of ACLA may have prognostic and therapeutic importance, and acute immunosuppressive therapy and plasmapheresis may be useful in patients with acute ischemic encephalopathy.
Abstract: The Hemostasis and Thrombosis Laboratory at the Oregon Health Sciences University identified 80 patients with significantly elevated anticardiolipin antibody (ACLA) levels. We reviewed all of their available medical records and found that 25 of these patients had associated neurological symptoms or disorders. These symptoms and disorders could be grouped into four distinct clinical patterns comprising encephalopathy, multiple cerebral infarctions, migraine-like headaches, and visual abnormalities including amaurosis fugax and ischemic optic neuropathy. Cerebral ischemia best explained these neurological dysfunctions. There was no correlation between the presence or absence of neurological disease and ACLA levels, but ACLA levels were higher in patients with encephalopathy than in others with neurological involvement (p less than 0.05). How neurological dysfunction and the presence of these antiphospholipid antibodies are related remains to be clarified. Nevertheless, in patients with unexplained cerebral ischemia, establishing the presence of ACLA may have prognostic and therapeutic importance. In particular, acute immunosuppressive therapy and plasmapheresis may be useful in patients with acute ischemic encephalopathy.
TL;DR: The results indicate a need to include aerobic fitness as a matched variable in future controlled studies of fibrositis and suggest that the "detraining phenomenon" may be of relevance to the etiopathogenesis of the disease.
Abstract: Aerobic fitness was evaluated in 25 women with fibrositis, by having them exercise to volitional exhaustion on an electronically braked cycle ergometer. Compared with published standards, greater than 80% of the fibrositis patients were not physically fit, as assessed by maximal oxygen uptake. Compared with matched sedentary controls, fibrositis patients accurately perceived their level of exertion in relation to oxygen consumption and attained a similar level of lactic acidosis, as assessed by their respiratory quotient and ventilatory threshold. Exercising muscle blood flow was estimated by 133xenon clearance in a subgroup of 16 fibrositis patients and compared with that in 16 matched sedentary controls; the fibrositis patients exhibited reduced 133xenon clearance. These results indicate a need to include aerobic fitness as a matched variable in future controlled studies of fibrositis and suggest that the "detraining phenomenon" may be of relevance to the etiopathogenesis of the disease.
TL;DR: In this article, vertical core samples were obtained from an impervious, unweathered, water-saturated clay deposit beneath a 5-year-old hazardous waste landfill at a site in southwestern Ontario.
Abstract: Vertical core samples were obtained from an impervious, unweathered, water-saturated clay deposit beneath a 5-year-old hazardous waste landfill at a site in southwestern Ontario. Sections of the cores were analyzed for chloride and volatile organic compounds. Waste-derived chloride was detected in the clay to a maximum depth of 83 cm below the bottom of the landfill. The most mobile organic compounds were found only to a depth of /approximately/ 15 cm. The downward transport of these chemical species into the clay was the result of simple Fickian diffusion. This study has implications for low-permeability clay liners used at waste disposal sites. For liners of typical thickness (/approximately/ 1 m), simple diffusion can cause breakthrough of mobile contaminants in approximately 5 years; the diffusive flux of contaminants out of such liners can be large.
TL;DR: In this article, the authors investigated the kinetics of the formation of manganese peroxidase compound I (MnPI) and of the reactions of MnPI with p-cresol and MnII.
Journal Article•
TL;DR: A method is described to reveal the relative predispositional effects (RPEs) of the HLA alleles or of any other marker system that is associated with a disease and a positive association with DR3 was confirmed as the strongest effect.
Abstract: A method is described to reveal the relative predispositional effects (RPEs) (predisposing, protective, or neutral) of the HLA alleles or of any other marker system that is associated with a disease. When the disease is associated with two or more alleles of a locus, the RPE method identifies the associations sequentially according to their strength; thus the problem that a strong association with one allele can create misleading deviations in the frequencies of other alleles is alleviated. Using this method, we have examined the relative effects of HLA-DR alleles in susceptibility to Graves disease in the Caucasian population. The well-established positive association with DR3 was confirmed as the strongest effect. In addition, a negative association was found between DR5 and Graves disease. The reduced frequency of DR5 among patients is statistically significant and is not a result of the increase in DR3. Finally, when patients were divided according to the presence or absence of eye disease, the latter showed a significant increase in the frequency of DR4. With family data, linkage to HLA of Graves disease was established in both Caucasian and Chinese families by the sib-pair method.
TL;DR: The best method for reducing secondary membrane formation and some types of glaucoma appears to be an extensive removal of the lens cortex, posterior capsule, and anterior vitreous.
TL;DR: The results demonstrate that significant electrical coupling occurs among locus coeruleus neurons from neonatal rats; this appears to decline with age, and the coupling serves as a low-pass filter and causes the synchronized occurrence of membrane potential oscillations.
Abstract: Locus coeruleus neurons in brain slices prepared from neonatal rats have rhythmic oscillations in membrane potential at frequencies ranging from 0.3 to 3 Hz. Recordings from pairs of neurons separated by 50–300 microns showed that this oscillatory activity was synchronized at ages less than 24 d. Slices cut from rats 24–27 d old showed rhythmic activity which was only partially synchronous between cell pairs, but full synchrony could be restored by superfusion with tetraethylammonium (2 mM) and/or barium (2 mM). No synchronous rhythmic activity was observed between neurons in slices from rats 40 d old, even in the presence of tetraethylammonium and barium. In those cells in which rhythmic potential oscillations were synchronous, action potentials occurring in one cell were not observed in the second cell. Electrotonic coupling was directly demonstrated between 41% of neurons (12 of 29 pairs) in slices from rats less than 10 d old but not in tissue from older rats (4 pairs). The input resistance of neurons from neonatal rats (less than 15 d old) was about half (81 M omega) that measured under identical conditions from neurons from adult rats (213 M omega). The electrotonic potential in cells from rats less than 15 d old was best fit by a double exponential, whereas that from adults was best fit by a single exponential. The results demonstrate that significant electrical coupling occurs among locus coeruleus neurons from neonatal rats; this appears to decline with age. The coupling serves as a low-pass filter and causes the synchronized occurrence of membrane potential oscillations. Such a rhythmic background activity within the entire nucleus may be important for the widespread trophic role of the noradrenergic neurons during development.
TL;DR: In situ hybridization of repeat-sequence DNA probes, specific to the paracentromric locus 1q12 and the telomeric locus1p36, to fluorescently stain regions that flank human chromosome 1p was used for fast detection of structural aberrations involving human chromosomes 1p in two separate experiments.
Abstract: SummaryWe have used in situ hybridization of repeat-sequence DNA probes, specific to the paracentromeric locus 1q12 and the telomeric locus 1p36, to fluorescently stain regions that flank human chromosome 1p. This procedure was used for fast detection of structural aberrations involving human chromosome 1p in two separate experiments. In one, human lymphocytes were irradiated with 0, 0·8, 1·6, 2·4 and 3·2 Gy of 137Cs γ-rays. In the other, human lymphocytes were irradiated with 0, 0·09, 0·18, 2·0, 3·1 and 4·1 Gy of 60Co γ-rays. The frequencies (per cell) of translocations and dicentrics with one breakpoint in 1p and one elsewhere in the genome were determined for cells irradiated at each dose point. These frequencies both increased with dose, D, in a linear-quadratic manner. The δ, α, and β coefficients resulting from a fit of the equation f(D) = δ + αD + βD2 to the translocation frequency dose-response data were 0·0025, 0·0027 and 0·0037 for 137Cs γ-rays, and 0·0010, 0·0041, and 0·0057 for 60Co γ-rays. Th...
TL;DR: Messenger RNA transcribed from RBK-1 in vitro directed the expression of potassium channels when it was injected into Xenopus oocytes and the potassium current through the expressed channels resembles both the transient and delayed rectifier currents reported in mammalian neurons and is sensitive to both 4-aminopyridine and tetraethylammonium.
Abstract: Potassium channels are ubiquitous membrane proteins with essential roles in nervous tissue, but little is known about the relation between their function and their molecular structure. A complementary DNA library was made from rat hippocampus, and a complementary DNA clone (RBK-1) was isolated. The predicted sequence of the 495-amino acid protein is homologous to potassium channel proteins encoded by the Shaker locus of Drosophila and differs by only three amino acids from the expected product of a mouse clone MBK-1. Messenger RNA transcribed from RBK-1 in vitro directed the expression of potassium channels when it was injected into Xenopus oocytes. The potassium current through the expressed channels resembles both the transient (or A) and the delayed rectifier currents reported in mammalian neurons and is sensitive to both 4-aminopyridine and tetraethylammonium.
TL;DR: The imipramine-clonidine combination was well tolerated and presents a promising treatment for severely depressed and traumatized patients, although further studies are needed.
Abstract: Some symptoms of posttraumatic stress disorder (PTSD) are related to central nervous system adrenergic hyperarousal. It has been suggested that an adrenergic receptor-blocker could be used to diminish, if not alleviate, the target symptoms of PTSD. Severely traumatized Cambodian refugee patients (N = 68) who suffered from chronic PTSD and major depression improved symptomatically when treated with a combination of clonidine and imipramine. A prospective pilot study of nine patients using this combination of an alpha-2 adrenergic agonist and a tricyclic antidepressant resulted in improved symptoms of depression in six patients, five to the point that DSM-III-R diagnoses were no longer met. The average decrease in the Hamilton Rating Scale for Depression score was 16. PTSD global symptoms improved in six patients but only in two to the point that DSM-III-R diagnoses were not met. There was no further sleep disorder in five and the frequency of nightmares lessened in seven patients. Startle reaction improved only in four patients; avoidance behavior showed little improvement in any of the nine. The imipramine-clonidine combination was well tolerated and presents a promising treatment for severely depressed and traumatized patients, although further studies are needed.
TL;DR: The results demonstrate that the proliferation in vitro of two normal cell types found in the skin can be influenced by aF GF and bFGF and demonstrate cell‐type specific differences in the responsiveness of fibroblasts and keratinocytes to these growth factors and heparin.
Abstract: Keratinocytes and fibroblasts isolated from human neonatal foreskin can be plated and grown through multiple rounds of division in vitro under defined serum-free conditions. We utilized these growth conditions to examine the mitogenic potential of acidic and basic fibroblast growth factor (aFGF and bFGF) on these cells. Our results demonstrate that both aFGF and bFGF can stimulate the proliferation of keratinocytes and fibroblasts. aFGF is a more potent mitogen than bFGF for keratinocytes. In contrast, bFGF appears to be more potent than aFGF in stimulating the growth of fibroblast cultures. Heparin sulfate (10 micrograms/ml) dramatically inhibited the ability of bFGF to stimulate the proliferation of keratinocytes. In comparison, heparin slightly inhibited the stimulatory effect of aFGF and had no effect on epidermal growth factor (EGF) stimulation in keratinocyte cultures. In fibroblast cultures the addition of heparin enhanced the mitogenic effect of aFGF, had a minimal stimulatory effect on the mitogenic activity of bFGF, and had no effect on EGF-stimulated growth. Our results demonstrate that the proliferation in vitro of two normal cell types found in the skin can be influenced by aFGF and bFGF and demonstrate cell-type specific differences in the responsiveness of fibroblasts and keratinocytes to these growth factors and heparin.
TL;DR: The mitogenic and immortalizing stages of erythroleukemia are now known to be caused by discrete genetic events--the first involving the SFFV env gene and the second involving the rare proviral integration sites.
Abstract: Friend virus induces rapid progressive erythroleukemia in susceptible mice. To oncologists and to cell biologists, this disease has provided a fascinating model for analyzing neoplastic progression, the role of host genes in controlling susceptibility to cancer, and the differentiation of erythroid cells in culture. However, to molecular biologists, Friend virus (and the closely related Rauscher and Cas virus complexes) has been generally viewed as a relatively complex anomaly. The virus lacks a classical oncogene of the sort typified by the src gene of Rous sarcoma virus. Such classical viral oncogenes (v-oncs) are modified versions of normal cellular genes (proto-oncogenes or c-oncs) and they are present in all of the other known retroviruses that cause rapidly developing neoplasms (Bishop 1983, 1985; Weinberg 1985). The c-oncs have been highly conserved throughout evolution, and there, is evidence that they perform important cellular functions. Because Friend virus lacks such a modified cellular gene and contains only retroviral-specific nucleic acid sequences, and because it induces a progressively developing neoplasm rather than an immediate cancer, it has been widely assumed that it is relatively “different” and “complex,” perhaps too different to provide general insights and too complex for molecular biological analysis.
01 Dec 1989
TL;DR: The results suggest that the early (one-hour) mechanical properties of the hybrid material exceed those of glass ionomer, and surface crazing, a documented problem with some glass ionomers when they become desiccated, is alleviated with this hybrid formulation.