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Biomedical subjects

W J Martin

Publications and source records attributed to W J Martin.

At least 73 records · Page 4Linked to original sources
PubMed1995

African green monkey origin of the atypical cytopathic 'stealth virus' isolated from a patient with chronic fatigue syndrome.

BACKGROUND: A cytomegalovirus-like 'stealth virus' had previously been isolated from a patient with the chronic fatigue syndrome (CFS). OBJECTIVE: To determine the original derivation of this virus. STUDY DESIGN: DNA sequencing of cloned regions of the virus was performed and the sequences were compared using BLASTN and FASTA analyses against the entire GenBank database. Viral sequences were also used to design primers for the polymerase chain reaction (PCR). RESULTS: DNA and amino acid sequence comparisons showed that the stealth virus was more closely related to the Colburn strain of simian cytomegalovirus (SCMV) than to CMV of either human or rhesus monkey origin or to any other sequenced herpesvirus. Similarity, but non-identity, between the stealth virus and SCMV, was confirmed using PCR. CONCLUSION: The findings implicate the African green monkey as the probable source of the virus isolated from this CFS patient.

Journal Article↗
PubMed1995

Cesarean section in a pregnant patient with an anterior mediastinal mass and failed supradiaphragmatic irradiation.

Nodular sclerosing Hodgkin's disease stages IA and IIA are the most common presentation of this disease during pregnancy. Patients presenting with late Hodgkin's disease with failed irradiation for cesarean section present a unique challenge. When this presentation occurs, a voluntary interruption of pregnancy is recommended. Upper body irradiation during the second trimester of pregnancy is recommended as well. We report a case involving a pregnant patient at 34 weeks' gestation presenting for cesarean section with a symptomatic anterior mediastinal mass occupying over 50% of the thoracic diameter. The anesthetic management was performed using continuous spinal.

Adult↗
PubMed1995

Acute encephalopathy induced in cats with a stealth virus isolated from a patient with chronic fatigue syndrome.

A simian cytomegalovirus-related stealth virus, isolated from a patient with the chronic fatigue syndrome, induced an acute neurological illness when inoculated into cats. Histological examination of brain tissue showed foci of cells with cytoplasmic vacuolization and an absence of any inflammatory reaction. Electron microscopy confirmed the presence of herpes-like viral particles and viral-like products in the brain of an inoculated animal. These findings support the role of stealth viruses in the pathogenesis of human neurological diseases and provide an animal model to evaluate potential antiviral therapy.

Acute Disease↗
PubMed1995

Murine laminin binds to Histoplasma capsulatum. A possible mechanism of dissemination.

Histoplasmosis, an increasingly important opportunistic infection in immunosuppressed subjects, is characterized by hematogenous dissemination of the yeast from the lung. The mechanism of this dissemination is not fully understood. Laminin, the major glycoprotein of the extracellular matrix, is known to mediate the attachment of various invasive pathogens to host tissues. In the current study, laminin is demonstrated to bind to Histoplasma capsulatum in a rapid, specific, and saturable manner. Scatchard analysis with 125I-labeled laminin revealed an estimated 3.0 x 10(4) binding sites per yeast with an apparent Kd for laminin binding of 1.6 x 10(-9) M. Laminin binding to H. capsulatum was decreased from 62 +/- 1 to 17 +/- 1 ng (P < 0.001) in the presence of 3,000 nM of Ile-Lys-Val-Ala-Val, a pentapeptide within one major cell attachment site of laminin. A 50-kD H. capsulatum laminin-binding protein was demonstrated using an 125I-Ln blot of H. capsulatum cell wall proteins. The 50-kD protein is also recognized by antibodies directed at the 67-kD laminin receptor, suggesting they are related. This study proposes a possible mechanism for H. capsulatum attachment to laminin, an important first step required for the yeast to recognize and traverse the basement membrane.

Amino Acid Sequence↗
PubMed1995

Interaction of vitronectin with Pneumocystis carinii: evidence for binding via the heparin binding domain.

Pneumocystis carinii pneumonia is a major opportunistic infection in patients with the acquired immune deficiency syndrome. P. carinii attachment to alveolar epithelial cells is considered necessary for growth and replication of the organism. Recent studies have focused on the role of adhesive proteins such as fibronectin and vitronectin in attachment mechanisms of P. carinii in the alveolar space. Whereas the role of fibronectin has been partially characterized, less is known about the mechanism of vitronectin interaction with P. carinii. To better understand the mechanism underlying this interaction, vitronectin-P. carinii binding was characterized with respect to monovalent and divalent cations and pH by using an iodine 125-labeled vitronectin binding assay to P. carinii. As an example, vitronectin-P. carinii binding was abolished in the presence of 1.0 mol/L NaCl and enhanced by Ca2+ and Mn2+. Further, periodate and heparin treatment of P. carinii significantly reduced vitronectin binding to the organism to 10% +/- 1.5% (p < 0.01) and 52% +/- 1.8% (p < 0.05) of control values, respectively. There was no competitive inhibition of vitronectin binding to P. carinii by using the peptide sequence arg-gly-asp-ser of the cell binding domain. The findings suggest that vitronectin, unlike fibronectin, binds to P. carinii by a predominantly electrostatic mechanism that likely involves the heparin binding domain of vitronectin.

Animals↗
PubMed1995

Role of surfactant protein A in the pathogenesis of tuberculosis in subjects with human immunodeficiency virus infection.

Human immunodeficiency virus (HIV)-infected subjects are at increased risk for tuberculosis even before there is a significant loss of CD4 lymphocytes. A factor was found to be present in the bronchoalveolar lavage (BAL) of HIV-infected subjects that promoted the attachment of M. tuberculosis (MTB) organisms to alveolar macrophages (AMs). Using 51Cr-labeled MTB organisms, BAL from control subjects resulted in MTB attachment to AMs at 11.6% +/- 1.0%; in contrast, BAL from HIV-infected subjects increased attachment to 33.1% +/- 3.8% (P < 0.001). Surfactant protein A (SP-A) levels in BAL of normal controls was 1.9 +/- 0.3 micrograms/ml and was 5.5 +/- 0.4 micrograms/ml in the BAL of HIV-infected subjects (P < 0.01). When SP-A was removed by immunoprecipitation from the BAL of HIV-infected subjects, MTB attachment decreased from 33.1% +/- 3.8% to 11.3% +/- 0.4% (P < 0.001), a value identical to control levels. Exogenous human SP-A (5 micrograms/ml) was added back to the immunoprecipitated BAL and the enhanced attachment of MTB was restored. These data suggest that BAL from HIV-infected subjects contain a factor that facilitates MTB attachment to AMs, the first critical step in the establishment of infection. This factor appears to be SP-A.

Animals↗
PubMed1994

Polymerase chain reaction heteroduplex polymorphism analysis by entangled solution capillary electrophoresis.

Heteroduplex DNA polymorphism analysis (HPA) makes use of conformational polymorphisms to alter electrophoretic mobility of fragments and can be used to detect non-restrictable loci. We have developed a novel application of entangled solution capillary electrophoresis (ESCE) to separate heteroduplex and homoduplex DNA molecules. The addition of ethidium bromide and glycerol to the free solution sieving buffer resulted in the improved peak resolution and good reproducibility. Reannealed polymerase chain reaction products could be used directly for mutation screening and with fully automated ESCE the entire HPA may be completed in less than 30 min including sample handling. This technology could provide a rapid and highly efficient way for screening rare mutations among large numbers of individuals.

Base Sequence↗
PubMed1994

Effects of sigma ligands on rat cerebellar Purkinje neuron firing: an iontophoretic study.

The electrophysiological responses of rat cerebellar Purkinje neurons to selective sigma ligands applied iontophoretically was examined in urethane anesthetized male Sprague-Dawley rats. 1,3-Di-o-tolylguanidine (DTG), dextrallorphan (DEX), (+)-pentazocine((+)-PENT), (+)-3-(3-Hydroxyphenyl)-N-propylpiperidine ((+)-3-PPP), and the novel diamine BD1008, were ejected from multibarrel pipettes onto individual Purkinje cells. In some neurons, cell firing was inhibited following ejections of all compounds. These inhibitory effects were dose dependent and occurred without changes in spike amplitude or duration, thus ruling out local anesthetic effects as a mechanism. (+)-3-PPP and DEX increased firing rate in 27% and 14% (n = 15, n = 14, respectively) of cells studied. The results of this study indicate that sigma ligands significantly alter the spontaneous firing of Purkinje neurons, consistent with previous work suggesting motor effects of sigma ligands via the rubro-cerebellar circuitry.

Animals↗
PubMed1994

Pathogenesis and host response in Pneumocystis carinii pneumonia.

Pneumocystis carinii (PC) pneumonia is recognized as the leading cause of opportunistic pulmonary infections in immunocompromised hosts during the past decade. Although much remains unknown about pathogenesis and host response in PC, recent years, studies of PC have provided us with an increasing base of knowledge about this organism and its relationship to the host. These studies have led to a better understanding of mechanisms of PC attachment and injury to host cells. New information about the interaction of PC with pulmonary surfactant provides insight about the pathophysiology of PC pneumonia. The interplay of the organism, host inflammatory cells, release of cytokines, generation of toxic metabolites, and involvement of both cellular and humoral immunity is complex, but understanding the pathogenesis of PC pneumonia is necessary in order to develop new therapies for this disorder.

Animals↗
PubMed1994

Isolation of Pneumocystis carinii gp120 by fibronectin affinity: evidence for manganese dependence.

Pneumocystis carinii is a major opportunistic lung pathogen and a leading cause of death among patients with the human immunodeficiency virus. Adherence of P. carinii to type I alveolar epithelial cells is essential for growth and replication and has been shown to be mediated in part by fibronectin (Fn). To better understand the mechanisms underlying this attachment, P. carinii-Fn interaction was characterized with respect to divalent and monovalent ion concentration and pH using an 125I-Fn binding assay to P. carinii. The results suggest that P. carinii has a receptor for Fn that was partially dependent on Ca2+, enhanced by Mn2+, and diminished somewhat by Mg2+. Additional data demonstrated that P. carinii-Fn interaction was sensitive to ionic strength. The pH profile revealed that P. carinii-Fn interaction increased with decreasing pH. The results from the binding assay provided the rationale for a simple isolation of the Fn receptor from P. carinii using a Fn-affinity column involving nondenaturing conditions. The isolated receptor appeared highly purified by SDS-PAGE analysis, with apparent molecular weights of 114 to 118 kD and 66 kD. Western blot analysis indicated that this receptor was gp120, a major surface glycoprotein of P. carinii. Furthermore, the isolated receptor inhibited Fn binding to P. carinii. Finally, a monoclonal antibody raised against the affinity-purified gp120 blocked Fn binding to P. carinii.

Animals↗
PubMed1994

Stealth viruses as neuropathogens.

Neuropsychiatric diseases viewed as multifaceted expression of a dysfunctional brain in which atypical responses are evoked by various sensory inputs. Disease entities have traditionally been classified according to the predominant manifestation ( ) without regard to the overlapping features of many of the diseases (+/-). Thus, mild to moderate pain, mood, cognitive, and neurosomatic symptoms are frequently present in chronic fatigue syndrome (CFS) patients. Fibromyalgia syndrome (FMS) is listed as an example of a predominantly chronic pain syndrome. Affect (mood) disorders include depression (Depress.), anxiety, panic reactions, blunted affect, mania, etc. Schizophrenia (Schizo.) is listed as an example of a major cognitive psychosis. Autism as well as various forms of dementia would be included in this category. Irritable bowel syndrome (IBS) is an example of a neurosomatic disease.

Adult↗
PubMed1994

Cytomegalovirus-related sequence in an atypical cytopathic virus repeatedly isolated from a patient with chronic fatigue syndrome.

An atypical virus, cytopathic for human and animal fibroblasts, was repeatedly cultured from a patient with chronic fatigue syndrome. Viral particles, suggestive of cytomegalovirus (CMV) were seen by electron microscopy. Infected cells did not, however, stain with antisera specific for CMV, herpes, simplex virus, or human herpes-virus-6. Polymerase chain reaction (PCR) assays for these viruses were also negative. Two distinct products of approximately 1.5 kilobase pairs were amplified from virally infected cells using the human T lymphotropic virus-II tax gene reactive primer, SK44, in low stringency PCR. Sequencing of one of the amplified products showed a region of highly significant partial homology with the UL34 gene of CMV. The sequence of the other PCR product did not correspond with CMV or any other virus. DNA was extracted from the material pelleted by ultracentrifugation of filtered culture supernatants. It migrated in agarose gels as a single band of approximately 20 kpb. The banded DNA was digested with EcoRI and cloned. A 2.2 kbp plasmid containing the CMV-related sequence identified within the PCR product was recovered. Sequencing of this plasmid extended the region of partial sequence homology with CMV to include a portion of the UL35 gene of CMV. Initial sequencing of additional plasmids has confirmed the partial relatedness to CMV. The data indicate a novel type of CMV-related "stealth" virus that is able to establish a clinically persistent human infection.

Adult↗
PubMed1994

Evidence for Pneumocystis carinii binding to a cell-free substrate: role of the adhesive protein fibronectin.

Attachment of Pneumocystis carinii organisms to the alveolar epithelium is probably a prerequisite for the initiation of P. carinii infection. Previous studies have demonstrated a role for the extracellular matrix protein fibronectin in mediating attachment of P. carinii organisms to cultured alveolar cells; however, these studies could not clearly distinguish the role of fibronectin binding to P. carinii organisms and fibronectin binding to the alveolar cells. The current study demonstrates the direct binding of P. carinii organisms to substrate-bound soluble fibronectin P. carinii organisms bound specifically in a concentration-dependent manner to fibronectin-coated plates; maximum binding (19.1% +/- 1.9%) occurred at a fibronectin concentration of 50 micrograms/ml. P. carinii organisms did not bind significantly to bovine serum albumin-coated plates (5.8% +/- 1.2%). Binding of P. carinii organisms to fibronectin-coated plates was inhibited in a concentration-dependent manner by addition of the tetrapeptide arginine-glycine-aspartic acid-serine, which represents the active site of the fibronectin cell-binding domain. Similarly, attachment of P. carinii organisms was significantly inhibited by the addition of monoclonal antibodies directed against the cell-binding domain of fibronectin or by the addition of calcium ion chelators. To evaluate the role of the major P. carinii surface antigen gp120 in attachment of P. carinii organisms, purified gp120 and specific polyclonal anti-gp120 antibodies were used to inhibit attachment of P. carinii organisms to fibronectin-coated plates.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1994

Cyclophosphamide-induced lung toxicity: mechanism of endothelial cell injury.

Cyclophosphamide (CP) is associated with significant pulmonary toxicity; however, the mechanism of toxicity is unknown. An in vitro endothelial model of injury was developed to assess the direct toxic effects of CP, CP derivatives and CP metabolites on cultured endothelial cells. Injury to 51Cr-labeled bovine artery pulmonary endothelial (BPAE) cells was quantified by the release of 51Cr from BPAE cells incubated for 18 h with injury expressed as a cytotoxic index. Because CP activation and metabolism occurs primarily in liver, assays assessing CP effects were conducted in the presence of an hepatic microsomal enzyme system. Upon activation, CP produces 4-hydroxycyclophosphamide, acrolein (ACR) and the alkylating metabolite, phosphoramide mustard. Nonactivated CP demonstrated no toxicity to BPAE cells within 18 h; whereas, activated CP induced significant BPAE cell injury in a concentration-dependent manner. Specific metabolites of CP 4-hydroxycyclophosphamide and ACR were markedly more toxic to BPAE cells than phosphoramide mustard. Sulfhydryl-rich compounds, S-2-(3-aminopropylamino)ethylphosphoric acid (WR-2721) and N-acetylcysteine, significantly reduced 4-hydroxycyclophosphamide- and ACR-induced injury but had no significant protective effect against phosphoramide mustard-induced toxicity. These studies suggest 1) CP is not metabolized within pulmonary artery endothelial cells, 2) ACR may be the principal CP metabolite involved in mediating direct injury to pulmonary artery endothelial cells and 3) sulfhydryl-rich agents may be effective in reducing CP-induced damage to critical endothelial cell barriers.

Acetylcysteine↗
PubMed1993

Antinociceptive actions of cannabinoids following intraventricular administration in rats.

Intraventricular administration of 5 or 20 micrograms of the cannabinoids WIN55,212-2 and CP-55,940 markedly reduced rat's responses to noxious thermal stimuli in the tail-flick test; no significant effect was found at 1 micrograms. The dose-response curves were steep and monotonic, the onset was rapid, and the effect lasted about an hour at the highest dose. In contrast to their antinociceptive actions, WIN55,212-2 and CP-55,940 failed to alter the latency of righting reflexes at the highest dose, suggesting that motor impairment did not cause the decreased responsiveness to the thermal stimulus. Finally, an assessment of the biodistribution of intraventricularly administered [3H]WIN55,212-2 in brain and spinal cord at the time of maximal antinociception revealed that the drug was confined to the brain. The levels of [3H]WIN55,212-2 found in S3-S4, the location of the spinal mechanisms for tail-flick, were below the limit of detectability. Together, these findings provide direct evidence that the antinociceptive effects of cannabinoids are mediated, at least in part, by their actions in the brain.

Analgesics↗
PubMed1993

Detection of human cytomegalovirus in ocular tissue by polymerase chain reaction and in situ DNA hybridization.

Rapid and sensitive techniques with a high degree of accuracy are necessary for the diagnosis and management of cytomegalovirus (CMV) retinitis presenting with atypical clinical manifestations. Light microscopy and immunohistochemical studies have limitations in the identification of this virus, but in situ DNA hybridization offers a rapid, highly specific, and easily interpretable means of identifying CMV. A new procedure of enzymatic amplification of DNA in vitro, called the polymerase chain reaction (PCR), has yielded excellent results in the identification of various viruses. In the study described herein, we evaluated the diagnostic usefulness of PCR and compared its reliability with that of in situ DNA hybridization for the detection of CMV in ocular tissues. We found that the reliability of the PCR method is similar to in situ DNA hybridization for the detection of CMV, although morphologic correlation is provided only by the latter technique. False-negative results can occur in PCR if the correct primer is not used.

AIDS-Related Opportunistic Infections↗