Biomedical subjects

R S Smith

Publications and source records attributed to R S Smith.

At least 19 recordsLinked to original sources

PubMed1992

Recidivism in an urban trauma center.

The incidence of recurrent injury requiring evaluation and treatment at an urban trauma center was assessed by examination of data from the registry of an urban trauma unit. A subgroup of 342 recidivists sustained 711 traumatic injuries. This represented 6.4% of trauma service activations or consultations. The rates of recurrence in random groups of 100 patients with trauma and 50 patients with traumatic deaths were 5% and 12%, respectively. These rates of recurrent injury are lower than those of several previous reports. Comparison of patients with recurrent episodes of trauma with patients who experience a single episode of trauma revealed significant differences in age, sex distribution, mechanism of injury, and fatal outcomes. Recidivists averaged only 7.9 months between episodes of injury. In patients with recurrent trauma with fatal outcomes, the mean interval between initial injury and death was 18.8 months. Early identification of patients at high risk for recurrence may provide an opportunity for behavior modification.

Adolescent↗

PubMed1992

Effect of dietary linoleic acid content on the distribution of triacylglycerol molecular species in rat adipose tissue.

The present study examined the effect of varying dietary linoleate intake (0.01, 0.24, 2.4, 24, 80 or 160 g/kg diet) for 24 weeks on the distribution of triacylglycerol (TG) molecular species in rat epididymal adipose tissue. Adipose TG fractions were purified by thin-layer chromatography and separated into different molecular species by reverse-phase high-performance liquid chromatography. The identification of TG species was based on fatty acid composition, retention time and the theoretical carbon number. When the dietary 18:2n-6 content was equal to or less than 24 g/kg, no significant amounts of n-6 fatty acids (mainly 18:2n-6) were observed in adipose tissue TG despite the fact that the levels of 20:4n-6 in liver phospholipids increased significantly. There were 12 major molecular species in adipose tissue when the dietary 18:2n-6 content was less than 2.4 g/kg. When the dietary 18:2n-6 content reached 24 g/kg, an additional six TG species containing one, two or three molecules of 18:2n-6 were observed. The levels of TG molecules containing two or three 18:2n-6 residues were further increased when the diet contained very large amounts of linoleic acid (160 g/kg). Conversely, those TG species containing only one 18:2n-6 residue became less abundant. It is suggested that the accumulation of these linoleate-rich TG molecular species in adipose tissue, particularly di- and trilinoleoyl containing TG, is the result of an adequate or an excessive intake of linoleic acid.

Adipose Tissue↗

PubMed1992

The GI T-lymphocyte theory of schizophrenia: some new observations.

Schizophrenic patients have low concentrations of PGE-1, n-6 fatty acids, vitamin C and zinc, elevated brain levels of dopamine and high plasma levels of interleukin-2 receptors (IL-2R). IL-2R plasma titers can be raised in celiac patients by administering wheat. These findings are both consistent with and supportive of the GI T-lymphocyte theory of schizophrenia.

Ascorbic Acid Deficiency↗

PubMed1992

A comprehensive macrophage-T-lymphocyte theory of schizophrenia.

Chronic macrophage activation with subsequent failure of activated macrophages to properly control T-lymphocyte secretion of interleukin-2 and interleukin-2 receptors is proposed as the basic biological mechanism of schizophrenia. Fundamental to this theory are the clinical observations on interleukin-2 provoking the active phase symptoms of schizophrenia in psychiatrically normal human volunteers and macrophage cytokines producing the prodromal and residual phase symptoms. This theory provides a completely new and unified mechanisms for the antipsychotic action of typical and atypical neuroleptics, bromocriptine, naloxone and DMSO. Furthermore, this hypothesis reveals why the dopamine theory of schizophrenia was a false lead. The effects of prolactin, estrogens and androgens are consistent with the model. Age of onset, male/female incidence, course of the disease from prodromal to active to residual phase, the protection afforded by rheumatoid arthritis and the close relationship between depression and schizophrenia can be explained by this theory. The gastrointestinal tract is suggested as the preferred site to investigate for the cause of the immune activation in schizophrenia.

Androgens↗

PubMed1992

The cytokine theory of headache.

Immune cell cytokines are proposed as the common mediators of headache. This unifying concept can not only account for headache, but also the prostaglandins, leukotrienes, platelet activating and vasoactive substances linked with headache, the varied symptoms associated with headache and the high incidence of headache with depression, infectious disease, trauma and in premenopausal women. The immune system as the central mediator of headache is consistent with the promoting effect of estrogen, the abortive activity of cortisol and the prophylactic properties of fish oil and evening primrose oil. This hypothesis provides a unified mechanism to explain headache triggered by food, infectious disease or trauma.

Cytokines↗

PubMed1992

Slow rehydration improves the recovery of dried bacterial populations.

Slow rehydration of bacteria from dried inoculant formulations provided higher viable counts than did rapid rehydration. Estimates were higher when clay and peat powder formulations of Rhizobium meliloti, Rhizobium leguminosarum biovar trifolii, and Pseudomonas putida, with water activities between 0.280 and 0.650, were slowly rehydrated to water activities of approximately 0.992 before continuing the dilution plating sequence. Rhizobium meliloti populations averaged 6.8 x 10(8) cfu/g and 1328 cfu/alfalfa seed greater when slowly rehydrated from bulk powder and preinoculated seeds, respectively. Bulk powder samples were slowly rehydrated to 0.992 water activity by the gradual addition of diluent, followed by a 10-min period for moisture equilibration. Preinoculated seed samples were placed in an environmental chamber at 24 degrees C with relative humidity greater than 80% for 1 h to allow moisture absorption. "Upshock," osmotic cellular stresses that occur during rehydration, was reduced when dried microbial formulations were slowly rehydrated and equilibrated before becoming fully hydrated in the dilution plating sequence. These procedures may also be applicable when estimating total viable bacterial populations from dried soil or other dry formulations.

Bacteriological Techniques↗

PubMed1992

Successful treatment of multiple organ system failure in a wartime environment: a case report from Operation Desert Storm.

Military weapons produce massive traumatic injuries. Multiple organ system failure can be expected to occur frequently as a result of such injuries. This case report from the recent conflict with Iraq is representative of wartime injuries and complications and the positive impact of modern intensive care capability on such injuries. Availability of critical care in future conflicts is essential.

Adult↗

PubMed1992

Argon laser fenestration of a Softperm contact lens.

Contact lens fenestration can increase tear exchange. We describe a case in which a patient with 15 D of against-the-rule astigmatism was fit with a Softperm contact lens but was unable to wear it for more than 1 hour because of corneal edema. After fenestrating the Softperm lens with an argon laser the patient was able to wear her lens for 10 hours without signs of corneal decompensation.

Aged↗

PubMed1991

Localization of an apolipoprotein A-I epitope critical for activation of lecithin-cholesterol acyltransferase.

Apolipoprotein (apo) A-I, the major apoprotein of human high density lipoprotein, is a vital cofactor for lecithin-cholesterol acyltransferase (LCAT), the plasma enzyme responsible for esterification of free cholesterol associated with high density lipoprotein. This esterification is an important component of the reverse cholesterol transport process. An immunochemical approach was used to test the hypothesis that a discrete region of apoA-I was important for LCAT activation. Three human apoA-I-specific monoclonal antibodies were found to inhibit LCAT activation in vitro in a manner directly proportional to their ability to bind to apoA-I-proteoliposomes in fluid phase immunoassays. This relationship was not observed with another four apoA-I-specific antibodies that also were able to bind to the apoA-I proteoliposomes. The use of synthetic peptides representing short amino acid sequences of the apoA-I molecule facilitated the identification of discrete but overlapping apoA-I epitopes for those antibodies that interfered with LCAT-mediated cholesterol esterification. These epitopes spanned amino acid residues 95-121 of mature apoA-I. Therefore, this region is most likely involved in the activation of LCAT by apoA-I.

Amino Acid Sequence↗

PubMed1991

Only multimers of a synthetic peptide of human apolipoprotein E are biologically active.

Plasma apolipoprotein E (apoE) is a ligand for the cellular uptake of cholesterol-rich plasma lipoproteins. ApoE also inhibits mitogen-stimulated lymphocyte proliferation and gonadotropin-stimulated ovarian theca/interstitial cell androgen production. To address the mechanism(s) by which apoE is active and to understand its interaction with the target cells, we prepared and examined the inhibitory activity of a series of apoE synthetic peptides. ApoE peptides representing amino acid residues 93-112, 141-155, 161-171, 172-182, and 174-193 were not active in either bioassay. However, specific inhibition of both lymphocyte proliferation and ovarian androgen production was observed with a self-conjugate of peptide-(141-155). Furthermore, a synthesized dimeric peptide representing two repeats of sequence-(141-155) (i.e. (141-155)-(141-155] was active as well. In both bioassays, the inhibition observed was not a result of direct cell killing. Furthermore, these apoE peptides exhibited activities with characteristics that were shared with those of native apoE. The results indicate that amino acid residues 141-155 of apoE are responsible for the biological activity of apoE. Furthermore, the results suggest that dimers or multimers of native apoE may be a biologically important species.

Amino Acid Sequence↗

PubMed1991

Reversal of rapid axonal transport at a lesion: leupeptin inhibits reversed protein transport, but does not inhibit reversed organelle transport.

The hypothesis that the reversal of rapid axonal transport requires a proteolytic conversion of anterograde transport vesicles was examined using sciatic nerve preparations from Xenopus laevis and leupeptin as an inhibitor of proteolysis. The transport of newly synthesized 35S-labeled proteins was studied with a position-sensitive detector of radiation. Organelle transport in isolated myelinated axons was studied by video microscopy. Leupeptin (0.1-0.4 mM) reduced the anterograde-to-retrograde reversal of protein transport adjacent to an axonal lesion. In experiments in which organelle transport was observed close to lesions in axons maintained in a medium compatible with intracellular function, 1.0 mM leupeptin inhibited neither the anterograde-to-retrograde nor the retrograde-to-anterograde reversal of organelle transport. In addition, in experiments in which conditions approximated those used to study protein transport, organelle transport away from the lesion was not inhibited by 1.0 mM leupeptin. A comparison of the morphology of rapidly transported organelles that underwent anterograde transport to the morphology of those that returned from a lesion (with or without the presence of leupeptin) provided no evidence that a morphological conversion was a necessary step in transport reversal.

Animals↗

PubMed1991

The role of G-protein in matrix-mediated motility of highly and poorly invasive melanoma cells.

Membranes from 2 K1735 murine melanoma clones of high invasive capacity show increased amounts of pertussis toxin (PT) substrate when compared to a weakly invasive cellular counterpart. Using a panel of specific G-protein antibodies, we identified Gi alpha 2 as the PT-sensitive G-protein uniquely abundant in highly invasive cells. In addition, RNA hybridization results confirm the immunoblot observations that Gi alpha 2 is present at higher levels in strongly invasive cells. This result suggests that the elevated expression of Gi alpha 2 in highly invasive cells is not entirely due to differences in either translational efficiency or protein degradation but is related to altered RNA transcriptional initiation, processing and/or degradation. ADP-ribosylation of Gi alpha-subunits by PT inhibited the fibronectin, laminin and collagen type-IV-stimulated motility of the 2 highly invasive clones, while PT treatment of cells from a poorly invasive clone resulted in little or no reduction of the fibronectin, laminin or collagen type-IV-stimulated lower motility. Furthermore, PT treatment of highly or poorly invasive K1735 clones does not result in any alteration in cellular cAMP accumulation, suggesting that the PT substrate is not linked with the adenylyl cyclase enzyme complex. The data suggest that a PT-sensitive G-protein, probably Gi alpha 2 regulates second messenger pathways that contribute to elevated motility in highly invasive K1735 cells.

Adenylate Cyclase Toxin↗

PubMed1991

Modification of liver fatty acid metabolism in mice by n-3 and n-6 delta 6-desaturase substrates and products.

The effects of dietary supplementation of either alpha-linolenic acid (18:3(n-3)) or stearidonic acid (18:4(n-3)) in combination with either linoleic acid (18:2(n-6)) or gamma-linolenic acid (18:3(n-6)) on liver fatty acid composition in mice were examined. Essential fatty acid deficient male C57BL/6 mice were separated into four groups of seven each and were fed a fat-free semi-purified diet supplemented with 1% (w/w) fatty acid methyl ester mixture (1:1), 18:2(n-6)/18:3(n-3), 18:2(n-6)/18:4(n-3), 18:3(n-6)/18:3(n-3), or 18:3(n-6)/18:4(n-3). After 7 days on the diets, fatty acid compositions in liver phosphatidylcholine and phosphatidylethanolamine fractions were analyzed. In groups fed 18:4(n-3) (18:2(n-6)/18:4(n-3) or 18:3(n-6)/18:4(n-3)) as compared to those fed 18:3(n-3) (18:2(n-6)/18:3(n-3) or 18:3(n-6)/18:3(n-3)), the levels of 20:4(n-3), 20:5(n-3) and 22:5(n-3) were increased, whereas those of 20:3(n-6) and 20:4(n-6) were decreased. When 18:3(n-6) replaced 18:2(n-6) as the source of n-6 acids, the levels of 18:3(n-6), 20:3(n-6), 20:4(n-6) and 22:5(n-6) were increased, whereas those of 20:4(n-3) and 20:5(n-3) were reduced. Replacing 18:3(n-3) by 18:4(n-3) reduced the (n-6)/(n-3) ratio by approx. 30%, whereas replacing 18:2(n-6) by 18:3(n-6) increased the (n-6)/(n-3) ratio by approx. 2-fold. These findings indicated that delta 6-desaturase products were metabolized more readily than their precursors. Both products also competed for the subsequent metabolic enzymes. However, the n-6 fatty acids derived from 18:3(n-6) were incorporated more favourably into liver phospholipids than n-3 fatty acids derived from 18:4(n-3).

Animals↗

PubMed1991

Production of a pokeweed antiviral protein (PAP)-containing immunotoxin, B43-PAP, directed against the CD19 human B lineage lymphoid differentiation antigen in highly purified form for human clinical trials.

We describe a standardized method for the preparation and purification of a potent immunotoxin against B-lineage leukemia/lymphoma cells, constructed with the ribosome inhibitory single chain plant toxin pokeweed antiviral protein (PAP) and a murine IgG1 monoclonal antibody (MoAb) specific for the human B lineage differentiation antigen CD19 for human clinical trials. PAP was prepared from spring leaves of Phytolacca americana plants by ammonium sulfate precipitation and purified to homogeneity by successive steps of ion exchange chromatography. B43 MoAb was produced in vitro by hollow fiber technology and purified to homogeneity by affinity chromatography. PAP toxin and B43 MoAb were modified via their free amino groups prior to their intermolecular conjugation. 2-iminothiolane was used to introduce reactive sulfhydryl groups into PAP and N-succinimidyl 3-(2-pyridyldithio) propionate was used to introduce 2-pyridyl disulfide bonds into B43 MoAb. Modified PAP was reacted with modified B43 MoAb resulting in a sulfhydryl-disulfide exchange reaction and yielding disulfide linked PAP-B43 MoAb conjugates, which we refer to as B43-PAP immunotoxin. B43-PAP immunotoxin was subjected to preparative gel filtration chromatography and cation exchange chromatography to obtain a highly purified, sterile, and pyrogen-free immunotoxin preparation with less than 5% free antibody contamination and less than 0.5% free PAP contamination. The final product displayed a high affinity for and a very potent anti-leukemic activity against B lineage leukemia cells. With slight modifications, the procedures detailed in this report should be generally applicable to preparation of other PAP-MoAb conjugates for treatment of cancer or AIDS.

Amino Acid Sequence↗

PubMed1991

The immune system is a key factor in the etiology of psychosocial disease.

The immune system is proposed as the key to understanding the etiology and treatment of psychosocial disease. There is a dense communication network between the immune system and the central nervous system (CNS). Immune cell cytokines, via direct action on the CNS, induce fever, alter sleep, pain perception and pituitary hormone release and reduce appetite and activity in animals. Interleukin-2 and interferon given to humans result in global behavioral and cognitive pathology. Activation of the immune system by pathogens produces global cognitive and behavioral pathology also. Recently, controlled trials have demonstrated that diet can cause psychosocial disease, presumably by an immune mechanism. Immune system abnormalities have been identified in manic-depressive psychosis, schizophrenia and alcoholism. Lithium carbonate is not only prophylactic for all three of these diseases, but it also powerfully stimulates the immune system. This is proposed as the mechanism of lithium's therapeutic effect. The antipsychotics, haloperidol and the phenothiazines, affect the immune system also. The rapid development of AIDS dementia complex can be explained by the remarkable influence the immune system has on the CNS.

AIDS Dementia Complex↗

PubMed1991

Is schizophrenia caused by excessive production of interleukin-2 and interleukin-2 receptors by gastrointestinal lymphocytes?

Excessive production of interleukin-2 (IL-2) and IL-2 receptors (IL-2R) by gastrointestinal (GI) T-lymphocytes is hypothesized as the cause of schizophrenia. It is based on: 1) IL-2 given to human volunteers can cause all the symptoms of schizophrenia; 2) GI lymphocytes in nonhuman primates produce much more IL-2 and IL-2R when stimulated than peripheral blood lymphocytes; 3) the GI tract is the largest lymphoid 'organ' in the body. The hypothesis appears to: 1) explain the protective effect of rheumatoid arthritis on schizophrenia; 2) make mechanistically plausible the findings on wheat and schizophrenia; 3) be consistent with and explain many of the known immunological abnormalities in schizophrenia.

Arthritis, Rheumatoid↗

PubMed1991

The macrophage theory of depression.

Excessive secretion of macrophage monokines is proposed as the cause of depression. Monokines when given to volunteers can produce the symptoms necessary for the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised (DSM-III-R) diagnosis of major depressive episode. Interleukin-1 (IL-1) can provoke the hormone abnormalities linked with depression. This theory provides an explanation for the significant association of depression with coronary heart disease, rheumatoid arthritis, stroke and other diseases where macrophage activation occurs. The 3:1 female/male incidence of depression ratio is accounted for by estrogen's ability to activate macrophages. The extraordinary low rate of depression in Japan is consistent with the suppressive effect of eicosapentanoic acid on macrophages. Fish oil is proposed as a prophylaxis against depression and omega-6 fat as a promoter. Infection, tissue damage, respiratory allergies and antigens found in food are some of the possible causes of macrophage activation triggering depression.

Arteriosclerosis↗

PubMed1991

The evolution of lymphadenopathy and hypergammaglobulinemia are evidence for early and sustained polyclonal B lymphocyte activation during human immunodeficiency virus infection.

To examine whether polyclonal activation of B lymphocytes as measured by hypergammaglobulinemia contributes to lymphadenopathy in human immunodeficiency virus (HIV) infection, correlates of adenopathy were examined in 240 homosexual men. Lymph node size was measured in 12 sites semiannually over 4 years. Both adenopathy and hyperglobulinemia developed within 1 year after seroconversion and persisted at high levels. Adenopathy declined near diagnosis of AIDS whereas serum IgG decreased 8-16 months after diagnosis. Adenopathy attributable to HIV occurred in all palpable node groups. By logistic regression, HIV-positive men were best discriminated from HIV-negative men by size of posterior cervical nodes and the number of sites with enlarged nodes. In a repeated measures model of covariance, adenopathy in HIV-positive men was associated with more CD4+ cells (P less than .002), elevated serum globulins (P less than .01), and lower platelet counts (P less than .05). Adenopathy declined over time (P less than .001) and with diagnosis of AIDS or AIDS-related complex (P less than .03). Thus, adenopathy and hypergammaglobulinemia are correlated and follow a similar course through various stages of HIV infection, suggesting that both are caused by polyclonal B cell activation.

AIDS-Related Complex↗