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Biomedical subjects

K McCarthy

Publications and source records attributed to K McCarthy.

At least 91 records · Page 5Linked to original sources
PubMed1991

Evidence for herpes simplex viral latency in the human cornea.

Patients undergoing penetrating keratoplasty for prior herpes simplex keratitis (group A) and corneal disease unrelated to herpes simplex (group B) were investigated to assess whether the cornea is a site for herpes simplex viral latency. All patients were seropositive for herpes simplex viral antibody. Virus was isolated from the tear film postoperatively in one patient and on cocultivation from the cornea of another patient. Herpes simplex viral DNA, however, was detected in the corneas of all patients from group A and half of those from group B by means of the polymerase chain reaction and primers to three well separated regions of the viral genome. Three donor corneas had no evidence of herpes simplex viral DNA. Using RNA polymerase chain reaction, we found evidence of a latency associated transcript and also that of a glycoprotein C coding transcript in two corneas, indicating viral replication. Nine corneas had evidence of a latency associated transcript but no glycoprotein C transcript, which suggests that herpes simplex virus may be maintained in a latent state in the corneas of patients with prior herpes simplex keratitis and in some patients with corneal disease unrelated to the herpes simplex virus.

Adult↗
PubMed1991

Accessory cells of the lung. II. Ia+ pulmonary dendritic cells display cell surface antigen heterogeneity.

In earlier studies, we had determined that class II (Ia) major histocompatibility complex (MHC) antigen expression in the normal rat lung was limited to dendritic cells and type II alveolar cells. In order to characterize the Ia+ pulmonary dendritic cells of the lung parenchyma, Lewis rat lungs were dissected free of their major airways, enzymatically digested, and serially subjected to density centrifugation on bovine serum albumin, overnight adherence, and immunopanning with a murine anti-rat monoclonal antibody (anti-OX-6) that reacts specifically with class II (Ia) MHC antigens. The purified Ia+ pulmonary cells displayed the morphologic and functional features of dendritic accessory cells, including extended cell processes, absence of nonspecific esterase staining, minimal phagocytosis of latex beads, rapid clustering with T lymphocytes, and co-stimulation of T-cell mitogen responses. Detailed immunophenotyping by cytofluorimetry and immunohistology showed that the purified dendritic cells were Ia (OX-6)+, CD45R (OX-1)+, CD45Rb (OX-22)-, ICAM-1+, and OX-43-. As many as 50% of the cells bound heat-aggregated IgG, while a smaller percentage expressed the CD43 sialophorin antigens (W3/13) expressed by a variety of blood-derived cells, and/or the OX-41 and RMA macrophage antigens. We conclude that Ia+ dendritic cells of lung are heterogeneous with respect to their expression of surface membrane differentiation antigens and may prove to be functionally distinct with respect to their accessory activities.

Animals↗
PubMed1990

Alphaherpesvirus saimiri infection in rabbits. 1. Light and electron microscopy study of cutaneous spinal nerves.

A light and electron microscopic study was undertaken to determine pathological changes in cutaneous spinal nerves of rabbits following intradermal inoculation with alphaherpesvirus saimiri (alpha HVS) isolate KM 322. Infected rabbits were killed at 3, 10, 17, 45 days and 2 years after infection. No abnormalities were seen at 3 days postinoculation. In the nerves of the rabbits killed at 10, 17 and 45 days after infection, axonal (Wallerian-type) degeneration was the main pathological feature. Regeneration, manifested by axonal sprouting, was observed in the nerves of the rabbits killed at 45 days post-inoculation. Neural fibrosis and paucity of unmyelinated axons was the final outcome. The severity of the neural damage not only varied according to the progression of the disease but between nerves taken from the same rabbit. This was probably associated with variation in the numbers of virus particles that had reached the dorsal root ganglion of the dermatome served by a particular nerve. Since alpha HVS (isolate KM 322) provides a model system for the study of virus latency in dorsal root ganglia, and consequently for the study of varicellazoster infection in man, these findings give further insight into the pathology of herpetic neuropathy.

Animals↗
PubMed1990

Alphaherpesvirus saimiri infection in rabbits. 2. Morphometric studies of cutaneous spinal nerves.

To provide a better insight into the ultrastructural pathology of herpetic neuropathy, quantitative studies were made on cutaneous spinal nerves of normal rabbits and rabbits intradermally infected with alphaherpesvirus saimiri (alpha HVS) isolate KM 322. Marked reductions in the numbers and densities of myelinated and unmyelinated axons were found in the nerves of the rabbits killed 17 and 45 days after the infection. Abnormalities in the size distribution of unmyelinated axons were seen at 45 days post-inoculation where axonal sprouting caused a noticeable shift in the fiber population. Two years after virus inoculation reduction in unmyelinated axons and abnormalities in the fiber size distributions characterized by smaller diameters of both myelinated and unmyelinated axons were detected. In these nerves conspicuous fibrosis caused a significant increase in the endoneurial area. At this stage of the infection regenerative changes involving myelinated fibers were found. Since attempts to detect spontaneous reactivation of alpha HVS infection in rabbits have been unsuccessful, the finding of regeneration 2 years after exposure seems in agreement with the view that regenerated myelinated fibers never attain their original size. In the present study although both types of fibers were damaged, morphometric data suggest that unmyelinated axons were more severely affected. Whether this seemingly selective involvement was due to spreading of the virus between axons sharing the same Schwann cell subunit remains to be proved.

Animals↗
PubMed1990

Endothelial leukocyte adhesion molecule 1: direct expression cloning and functional interactions.

A cDNA for endothelial leukocyte adhesion molecule 1 (ELAM-1) was isolated by transient expression in COS-7 cells of a subtracted cDNA library from cytokine-treated human umbilical vein endothelial cells (HUVECs), with selection of ELAM-1-expressing clones by adhesion of transfected cells to the human promyelocytic cell line HL-60. This cloning method requires neither antibody nor purified ligand. ELAM-1-expressing COS cells bind the promyelocytic cell line HL-60 by a Ca2(+)-dependent but temperature-independent mechanism. Although ELAM-1 is homologous to mammalian lectins, its interaction with HL-60 cells is not inhibited by simple carbohydrate structures. ELAM-1-expressing COS cells also bind human neutrophils and the human colon carcinoma cell line HT-29, but not the B-cell line Ramos. However, Ramos cells adhere to cytokine-treated HUVECs but not control HUVECs, confirming the existence of other inducible adhesion molecules. In addition, the binding of HL-60 cells or neutrophils to ELAM-1-expressing COS cells is not inhibited by a monoclonal antibody (60.3) directed to an inhibitory epitope on CD18, indicating that the ELAM-1 ligand, although uncharacterized, is not a member of the CD11/CD18 family.

Amino Acid Sequence↗
PubMed1990

Ocular shedding of herpes simplex virus.

The presence, frequency, and relationship of ocular and oral shedding of herpes simplex virus to previous herpes keratitis was investigated. This was to determine if a history of herpes keratitis predisposes to shedding of the herpes simplex virus into the tear film and/or mouth. Swabs were collected from the eyes and mouth of two groups of patients thrice weekly over a two- to four-month period. Group A comprised nine patients with a history of herpes labialis, group B 15 patients with a history of herpes keratitis. Herpes simplex virus type 1 was isolated from 1.33% of mouth specimens but was not identified in any of the ocular specimens. There was no significant difference between groups A and B in terms of ocular or oral shedding. Oral shedding appears to be independent of a previous herpes keratitis. The tear film is an unlikely source of virus in persons either with no history of herpes keratitis or between attacks in those patients with a history of previous herpes keratitis.

Adult↗
PubMed1990

Anti-RMA: a murine monoclonal antibody that activates rat macrophages. I. Distribution and characterization of the RMA antigen.

Activated macrophages participate in inflammation by eliminating foreign cells, promoting wound healing, and modulating the immune response. A murine monoclonal antibody, designated anti-rat macrophage activator (RMA), was raised against alveolar macrophages (AM) activated with interferon-gamma (IFN-gamma) and phorbol myristate acetate (PMA). The RMA antigen is expressed by resident macrophages but not by other cells. Binding to AM by anti-RMA is not competitively inhibited by the murine monoclonal antibodies MRC OX-41, OX-42, and OX-43. Surface membrane expression of RMA antigens is upregulated by lipopolysaccharide, PMA, and tumor necrosis factor-alpha but not by IFN-gamma. Stimulation of AM with anti-RMA yields distinct ultrastructural alterations, as well as de novo protein and DNA synthesis. Immunoprecipitation of [35S]methionine metabolically labeled AM yields a 120 kD protein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that is not altered by chemical reduction. We conclude that the RMA antigen is macrophage specific and that binding of anti-RMA to AM promotes functional activities in a subset of these cells.

Animals↗
PubMed1990

Anti-RMA, a murine monoclonal antibody, activates rat macrophages: II. Induction of DNA synthesis and formation of multinucleated giant cells.

Anti-RMA is a murine anti-rat monoclonal antibody that binds to a 120-kD surface membrane antigen expressed primarily by alveolar macrophages. Saline-lavaged alveolar macrophages (AM) formed clusters after incubation with anti-RMA. Anti-RMA produced multinucleated giant cells (MGC) in approximately 15% of adherent AM, and the F (ab')2 fragment of anti-RMA yielded MGC in approximately 9% of AM. The Fab fragment of anti-RMA did not promote MGC formation, nor did the murine anti-rat monoclonal antibodies OX41 and W3/25 (anti-CD4). Although anti-RMA produced a tenfold increase in [3H]thymidine incorporation by AM, it yielded a minimal increase in the number of AM. Autoradiography of AM stimulated with anti-RMA showed heterogeneous labeling of nuclei in MGC, suggesting that 3H-labeled AM may fuse with AM that are not actively synthesizing DNA. These findings suggest that binding of anti-RMA to AM may activate DNA synthesis, and promote clustering and fusion of AM, leading to MGC formation.

Animals↗
PubMed1989

Evaluation of a cancer pain model for the testing of long-acting analgesics. The effect of MS Contin in a double-blind, randomized crossover design.

A double-blind, double-dummy, crossover study compared oral controlled-release morphine sulfate (MS Contin tablets [MSC], Purdue Frederick, Norwalk, CT) every 12 hours, and immediate-release morphine sulfate (IRMS) tablets, every 4 hours, in 14 evaluable patients with chronic cancer pain. The test model described showed assay sensitivity for steady-state analgesia, requiring relatively few subjects to yield statistical significance in pharmacologic potency estimates. Initial doses were the calculated equivalents of about one third the previous opioid requirements or at least 30 mg MSC every 12 hours or 15 mg IRMS every 4 hours. This was generally subtherapeutic; hence, additional IRMS was available for break-through pain. Doses of MSC and IRMS were titrated upwards until the requirement for rescue IRMS was less than 20% of the total daily amount of morphine. In both study phases, the total dose of morphine increased significantly from the first day to the last, on which it was significantly (34%) higher for IRMS than MSC. Pain was significantly less intense and frequent in the last 24 hours of each treatment arm than in the first, and equally well controlled by both regimens. The two treatments were equipotent in a pharmacologic assay using dosages and pain scores. The requirement for rescue analgesia was similarly comparable for both treatments, decreasing significantly with upward dose titration. The few side effects experienced (one with MSC and three with IRMS) did not include serious reactions such as respiratory depression. It is concluded that MSC, 12-hourly, controls cancer pain as effectively and safely as IRMS on a 4-hour schedule. MS Contin exhibits a 12-hour duration of action as previously shown in other well-controlled trials. A problem of pain exacerbation at the start of each study phase was found to be associated with the design of this study. It may be resolved with a higher initial study dose and/or use of a patient-controlled analgesia device for parenteral rescue doses.

Administration, Oral↗
PubMed1989

Carcinoma arising in a pleomorphic adenoma of the epiglottis.

Despite the abundance of minor salivary glands within the larynx, pleomorphic adenomas are rarely found. It is therefore not surprising that there are few reports of malignant mixed tumours in this site. We describe a case of carcinoma arising in a pleomorphic adenoma of the epiglottis which, to our knowledge, has not been described previously. The patient underwent a horizontal partial laryngectomy and functional neck dissection and is well one year postoperatively. We feel this represents a suitable approach to treatment for this rare tumour.

Adenocarcinoma↗
PubMed1989

The effects of 5-azacytidine, 12-O-tetradecanoylphorbol 13-acetate and sodium n-butyrate on reactivation of alphaherpesvirus saimiri from explant cultures of latently infected rabbit dorsal root ganglia.

The DNA hypomethylating agent 5-azacytidine greatly increased the reactivation of alphaherpesvirus saimiri-1 (alpha HVS) from latently infected rabbit dorsal root ganglia, although it inhibited the virus yield and plaque formation efficiency of alpha HVS in Vero cells. 12-O-Tetradecanoylphorbol 13-acetate (a protein kinase C activator) and sodium n-butyrate both had a stimulating action on replication in Vero cells but did not affect the release of alpha HVS from latently infected rabbit dorsal root ganglia.

Animals↗
PubMed1989

Tumor-associated aphasia in left hemisphere primary brain tumors: the importance of age and tumor grade.

Although one-quarter of patients with primary brain tumors have language disturbances at the time of initial presentation, the factors contributing to their aphasia are not clear. A group of 32 patients with primary tumors of the left hemisphere was collected retrospectively and the relationship between clinical, radiographic, and pathologic factors and tumor-associated aphasia was examined. We assessed language function before beginning any treatment including steroids. The factor that best predicted language disturbance was greater patient age; the only other significant factor was tumor grade. Tumor size made a nearly significant impact, but tumor location within the left hemisphere did not correlate with aphasia.

Adult↗
PubMed1989

Noninvasive monitoring of oxygen and carbon dioxide.

New technologies for the noninvasive assessment of oxygen and carbon dioxide are transforming clinical practice. Transcutaneous monitoring of PO2 (PtcO2) and PCO2 (PtCO2) provides an approximation of PaO2 and PaCO2 values in hemodynamically normal individuals, but both PtcO2 and PtcCO2 diverge from the corresponding arterial values when cardiac output is reduced, even in the absence of hypotension. Transcutaneous monitors also have relatively slow equilibration and response times. Pulse oximeters rapidly assess arterial O2 saturation, but give spurious results when dyshemoglobins (for example, carboxyhemoglobin, methemoglobin) are present in significant quantity. End-tidal CO2 (PetCO2) monitoring tracks breath-by-breath changes in ventilation, and PetCO2 approximates PaCO2 when significant physiologic dead-space is not present. Respiratory inductive plethysmography provides a semiquantitative assessment of tidal volume and the relative contribution of the thorax and abdomen to ventilation; among other uses, this technology may allow for the early detection of respiratory muscle fatigue prior to the onset of respiratory failure.

Blood Gas Monitoring, Transcutaneous↗
PubMed1989

Nonthromboembolic causes of high-probability lung scans.

Three cases of high-probability lung scans because of nonthromboembolic causes (dissecting thoracic aortic aneurysm, sarcoid with venous occlusion, and subclavian catheter misplacement) are presented along with a review of the literature.

Adult↗
PubMed1988

Alphaherpesvirus saimiri in rabbits: a model for human encephalitis?

One (KM91) of a series of isolates of alphaherpesvirus saimiri (alpha HVS) produced rapidly fatal encephalitis in rabbits following intradermal infection, whereas the others (KM180, KM322 and KM338) were non-lethal and produced ganglionitis and prolonged latency. Alphaherpesvirus saimiri KM91 initially produced ganglionitis but quickly ascended the spinal cord to the brain causing death 10 days post-infection. Prior infection with any of the three benign isolates or inoculation with beta-propiolactone (beta PL)-inactivated alpha HVS KM91 protected rabbits from lethal encephalitis when they were subsequently challenged with a lethal dose of alpha HVS KM91. Each of 20 rabbits co-inoculated in the same site with a lethal dose of alpha HVS KM91 and either alpha HVS KM322 (1.5 X 10(3) to 1.5 X 10(5) p.f.u.) or beta PL-inactivated alpha HVS KM322 (1 X 10(7) p.f.u. equivalents) survived. In contrast only half of those co-inoculated with alpha HVS KM91 and beta PL-inactivated alpha HVS KM91 (1 X 10(7) p.f.u. equivalents) survived. Co-inoculation of lethal alpha HVS KM91 (75 p.f.u.) and benign alpha HVS KM322 (1.5 X 10(3) p.f.u.) into opposite flanks resulted in protection from encephalitis in one of four rabbits. Alphaherpesvirus saimiri KM91 was shown to have the capacity to become latent in dorsal root ganglia if the rabbit did not die.

Animals↗