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Biomedical subjects

C G Ray

Publications and source records attributed to C G Ray.

At least 19 recordsLinked to original sources
PubMed1992

Bronchoalveolar lavage fluid cytology reflects airway inflammation in beagle puppies with acute bronchiolitis.

Beagle puppies infected with both canine parainfluenza virus type 2 (CPI2) and Bordetella bronchiseptica (Bb) develop more severe acute bronchiolitis and airways hyperresponsiveness than do those infected with CPI2 or Bb alone. The aim of our study was to characterize the inflammatory response associated with airway hyperresponsiveness, and to determine whether the inflammatory cell response of bronchoalveolar lavage fluid (BALF) reflected changes in the bronchioles in this model. We investigated 25 beagle puppies (ages 76 +/- 5 days, mean +/- SEM) in four groups: controls (n = 6), or puppies inoculated with both CPI2 and Bb (CPI2-Bb) (n = 11), with only CPI2 (n = 4), or only Bb (n = 4). The puppies were killed 3-4 days after inoculation, the lungs excised, the intermediate lobe lavaged, and BALF and the bronchiolar wall tissue examined for neutrophils and other inflammatory cells. Control puppies had no evidence of inflammation. However, the CPI2-Bb puppies had developed cough and rhinitis, positive cultures for CPI2 and Bb, and a neutrophilic cellular response in both the bronchioles and the BALF. Puppies inoculated with only CPI2 or Bb had milder illnesses and no significant bronchiolar and BALF neutrophilic response. For all groups, the severity of bronchiolar wall inflammation correlated with the total number of BALF inflammatory cells, and bronchiolar wall neutrophil counts correlated with the percentage of neutrophils in the BALF. The illness and the airway hyperresponsiveness observed in the CPI2-Bb group were associated with airway neutrophilia. Our studies support the hypothesis that neutrophils are associated with airway dysfunction in this model, and the use of BALF to study the process.

Acute Disease↗
PubMed1992

Expression of type IV collagenase correlates with the invasion of human lymphoblastoid cell lines and pathogenesis in SCID mice.

An in vitro model, called the Membrane Invasion Culture System (MICS), was used to study the invasive potential of an Epstein-Barr virus (EBV) positive lymphoblastoid cell line (LCL), an EBV-negative Burkitt lymphoma (BL) cell line of American origin and an EBV-positive BL of African origin. MICS measured the ability of these cell lines to invade reconstituted basement membrane-coated filters, which correlated with their tumorigenic and metastatic capabilities in a SCID mouse model. Furthermore, the significantly greater invasive behaviour of the EBV-positive LCL was directly correlated with the cells' ability to express and secrete human type IV collagenase (72 kDa), an important metalloproteinase responsible for the degradation of collagen IV in basement membranes. The data suggest that MICS and the SCID mouse are useful tests of tumorigenicity in lymphoid cells, with measurable effects in both systems related to human type IV collagenase activity. Both models allow further exploration of malignant phenotypes associated with EBV transformation of lymphoid tissues.

Animals↗
PubMed1992

Effects of a melanotropic peptide on melanoma cell growth, metastasis, and invasion.

Melanocyte stimulating hormone (alpha-MSH, alpha-melanotropin),Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Ly-Pro-Va l-NH2, regulates melanogenesis within epidermal melanocytes of many animals. An MSH analogue ([Nle4,D-Phe7]alpha-MSH) that exhibits superpotency and prolonged biological activity has been synthesized, biologically characterized, and is presently in clinical trials to determine its possible clinical use in tanning of the skin. It also has potential for the diagnosis, localization, and chemotherapy of melanoma. The effects of this analogue on the growth, metastatic behavior, and invasive potential of a melanotic variant of Cloudman S-91 murine melanoma are reported here. In an intracutaneous murine model of melanoma cell tumor growth, the analogue did not increase primary tumor growth (size) after the period of administration of the peptide hormone analogue and did not affect spontaneous lung metastases. Survival times for the control and melanotropin-treated groups were similar, suggesting that overall tumor burden was not affected by treatment with the hormone analogue. Last, melanoma cell invasion through a human amniotic basement membrane in vitro was not enhanced compared to untreated cells.

Amino Acid Sequence↗
PubMed1992

The predictive relationship between serum IgE levels at birth and subsequent incidences of lower respiratory illnesses and eczema in infants.

Cord serum IgE levels are predictive of subsequent atopic diseases early in life. Lower respiratory illnesses (LRI) have often been included with atopic diseases in infancy but have not been examined as a separate entity for a relation to cord IgE levels. Among 767 healthy newborns in Tucson, Arizona studied longitudinally, cord serum IgE levels were directly related to the subsequent incidence of eczema. In contrast, the incidence of LRI not only failed to show a direct relationship to IgE levels but actually decreased with increasing cord IgE levels from 34.8% in the lowest cord IgE group to 22.2% in the highest IgE group (greater than 1.0 IU/ml IgE; p for trend chi-square less than 0.03). Limiting LRI to those with wheeze did not alter the inverse relationship with IgE levels. The inverse LRI-IgE relationship was strong for non-RSV LRI, whereas RSV LRI had neither a direct nor an inverse relationship. These inverse LRI-IgE relationships were significant for LRI occurring in infants before but not after 6 months of age. Maternal (but not paternal) allergic history was associated with higher cord IgE levels and with an increased incidence of LRI, the latter effect being independent of IgE. This study suggests that most LRI in the first year of life are not early manifestations of an allergic predisposition.

Arizona↗
PubMed1991

Risk factors for respiratory syncytial virus-associated lower respiratory illnesses in the first year of life.

The relation of breast feeding and other factors to the incidence of respiratory syncytial virus-associated lower respiratory tract illness (RSV-LRI) in the first year of life is examined. The study population is 1,179 healthy infants enrolled at birth between May 1980 and January 1984 into the Tucson Children's Respiratory Study, Tucson, Arizona. Each subject's data were assessed at each month of age during the first year of life, during those months when respiratory syncytial virus was isolated. A number of significant relations were observed, particularly between 1 and 3 months of age. At this age, the risk of having a RSV-LRI increased in association with less than 1-month or no breast feeding, with being male, and with increasing numbers of others sharing the child's bedroom. In multivariate analysis, only sex and the number of others sharing the room remained as significant direct effects. However, a significant interaction demonstrated that breast feeding has a protective role in relation to RSV-LRIs for those infants of mothers with a lower education level. The risk of having a RSV-LRI increases with combinations of risk factors. Being in day care was a significant risk factor in the 7- to 9-month age range. The RSV-LRI rate also varies by birth month. A separate case-control study assessed relations of RSV-LRIs with cord serum RSV antibody. Those with lower cord serum RSV antibody, who also have minimal breast feeding, were found to be especially at risk for RSV-LRIs in the first 5 months of life.

Antibodies, Viral↗
PubMed1991

Changes in lung mechanics and histamine responsiveness after sequential canine adenovirus 2 and canine parainfluenza 2 virus infection in beagle puppies.

We determined the effects of an immediately antecedent viral lower respiratory tract infection (LRI) on the severity of clinical illness, changes in lung function and airway histamine responsiveness produced by a subsequent LRI in 9-12 week old beagle puppies inoculated with canine adenovirus 2, followed in 2 weeks by inoculation with canine parainfluenza 2 virus (CAV2-CP12, n = 7). We compared their acute responses to puppies infected with CP12 alone (n = 5), CAV2 alone (n = 7), and no infection (control, n = 6). Puppies inoculated with either virus alone developed a LRI 3 to 6 days after inoculation which resolved by 12-14 days after inoculation. However, the illness was more severe in the CAV2 group. In the CAV2-CP12 group, CP12 infection following CAV2 infection resulted in a clinical illness nearly comparable to that observed with CAV2 alone. Whereas in control and CP12 puppies, lung resistance (RL) decreased and dynamic lung compliance (Cdyn) increased during the study due to normal growth, RL increased and Cdyn remained unchanged in the CAV2 group. In contrast, RL did not change and Cdyn increased in the CAV2-CP12 group. Airway histamine responsiveness in the CAV2-CP12 group increased during infection with CP12 and was similar to that observed with CAV2 alone. In contrast, infection with CP12 alone produced a small, but non-significant increase in histamine responsiveness. The duration of the increase in histamine responsiveness was not prolonged in the CAV2-CP12 group in comparison to CP12 or CAV2 alone. However, the length of clinical illness was extended in the CAV2-CP12 group in comparison to the other infected groups. These data suggest that an immediately antecedent viral LRI can potentiate the clinical and physiologic effects of a subsequent viral LRI.

Adenoviridae Infections↗
PubMed1991

Use of immunofluorescence to identify measles virus infections.

Monoclonal antibody to measles virus was used successfully to identify measles virus antigen directly in clinical specimens, as well as in cell cultures. Pooled nasopharyngeal-throat swab specimens had a higher yield than throat swabs or urine samples for virus detection. Use of A549 cell cultures in the spin amplification vial assay proved to be highly efficient, allowing virus recognition within 1 to 2 days of inoculation. A combination of appropriately collected specimens, which includes a nasopharyngeal-throat swab, direct antigen detection with monoclonal antibody to measles in an indirect immunofluorescence system, and the spin amplification vial assay using A549 cells provides a sensitive and rapid system for isolation and/or identification of measles virus infections.

Antibodies, Monoclonal↗
PubMed1990

Hemodialysis clearance of intravenously administered ribavirin.

A patient with an implanted artificial heart, acute, anuric renal failure, and disseminated influenza virus type A infection received intravenous ribavirin. Drug elimination by hemodialysis was measured. Plasma dialysis clearance averaged 93.9 +/- 8.6 ml/min. The maximum amount of ribavirin removed from the body during one period of hemodialysis was 79.1 mg. Ribavirin is not removed in important quantities by hemodialysis.

Adult↗
PubMed1990

Changes in lung mechanics and reactivity with age after viral bronchiolitis in beagle puppies.

We measured changes with growth in lung function and airway reactivity after acute canine parainfluenza virus type 2 (CPI2, n = 5), canine adenovirus type 2 (CAV2, n = 7), and sequential CAV2-CPI2 (n = 6) infections or no infection (controls, n = 6) in beagle puppies (age approximately 79 days). In the CPI2 and CAV2 groups, a lower respiratory illness developed by day 3 postinfection with clinical recovery by day 14. In the CAV2-CPI2 group, puppies were inoculated initially with CAV2 and 12 days later with CPI2. In this group, illness persisted until day 14 after infection with CPI2. Lung resistance (RL), dynamic (Cdyn) and static (Cst) lung compliance, functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured before infection and at periodic intervals until 239 +/- 43 days of age. Lung function data were analyzed using a longitudinal random effects model. In all groups, FRC, Cst, and Cdyn increased with age. In all infected groups, the regression slopes for Cdyn were steeper than in controls. RL decreased linearly with age without group slope differences. Histamine reactivity increased with age, but there were no differences in slope among groups. Lung pathological studies showed areas of obliterative bronchiolitis and chronic small airways inflammation particularly in the CAV2 and CAV2-CPI2 groups. Thus, viral bronchiolitis produces chronic small airways inflammation in beagle puppies and alters the changes in lung function occurring with growth. Histamine reactivity increases with age and is not modified by viral infection.

Adenoviridae Infections↗
PubMed1990

Canine parainfluenza type 2 bronchiolitis increases histamine responsiveness in beagle puppies.

Histamine hyperresponsiveness with viral bronchiolitis may depend on previous exposures to viruses or to other pathogens. We studied 32 outbred beagle puppies 80 to 155 days of age who were raised in isolation and who were specific pathogen-free. Puppies were inoculated with canine parainfluenza type 2 (CPI2, n = 8), Bordetella bronchiseptica (Bb, n = 7), or both CPI2 and Bb (CPI2-Bb, n = 9). Control puppies (C, n = 8) were not inoculated. The puppies were anesthetized with sodium thiopental (5 mg/kg) and chloralose (80 mg/kg) and were ventilated mechanically. Lung resistance (RL), dynamic lung compliance (Cdyn), functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured 3 days prior to inoculation (Day -3), on the day of inoculation (Day 0), and on Days 3-4, 6, 8-10, and 12-14 after inoculation. Histamine responsiveness was measured as: (1) the concentration of histamine base that increased RL to 150% (PC 150% RL) or decreased Cdyn to 75% (PC 75% Cdyn) of the response to saline (RL sal and Cdyn sal, respectively), and (2) the change in RL or Cdyn after inhalation of 11 mg/ml of histamine when compared with RL sal and Cdyn sal. On Day 0 there were no significant (p greater than 0.05) differences among groups with regard to age-corrected weights, FRC, RL, Cdyn, or histamine responsiveness. Control puppies remained healthy, and their pulmonary function and histamine responsiveness did not change. CPI2-Bb puppies increased RL and decreased FRC on Day 3-4, and were moderately ill and histamine-hyperresponsive on Day 3-4 and on Day 6.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1990

Acute canine adenovirus 2 infection increases histamine airway reactivity in beagle puppies.

Acute infection with canine adenovirus was studied in 23 specific pathogen-free outbred beagle puppies (median age = 78 days, range = 67 to 86 days) to determine its effects on pulmonary function and airway responsiveness to aerosolized histamine. The following groups were studied: uninoculated (n = 6, Control); inoculated with canine adenovirus type 2 (CAV2) (n = 11, Infected); and subclinical spontaneous infection with CAV2 (n = 6, Subclinical). While anesthetized with chloralose and mechanically ventilated, lung function and responsiveness to aerosolized histamine were measured 3 days before inoculation (Day -3), the day of inoculation (Day 0), and 3 to 4 (Day 3-4), 6 (Day 6), 8 to 10 (Day 8-10), and 12 to 14 (Day 12-14) days after inoculation. Histamine responsiveness was assessed by calculating the provocation concentration of histamine diphosphate to increase lung resistance (RL) to 150% (PC 150% RL), or decrease dynamic lung compliance (Cdyn) to 75% (PC 75% Cdyn) of the response to saline [RL(sal) and Cdyn(sal), respectively]. Arterial blood gases, functional residual capacity (FRC), specific static lung compliance (spCst), RL, Cdyn, and histamine responsiveness were not significantly different on Day 0 among the groups (p greater than 0.05). Control and Subclinical puppies remained healthy, had a mean weight gain of 0.7 kg, and did not change their histamine responsiveness during the study period. Infected puppies developed moderate to severe clinical illnesses, had poor weight gain, and were histamine hyperresponsive on Days 3-4 and 6. One infected puppy died on Day 3-4, and two died on Day 6 of their illness.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

Localization of inflammation and virions in canine adenovirus type 2 bronchiolitis.

Beagle puppies develop bronchiolar inflammation and histamine hyperresponsiveness with canine adenovirus type 2 (CAV2) infections. We determined the distribution of bronchiolar lesions and correlated inflammation with virions and bronchoalveolar lavage fluid (BALF) cytology. Nineteen beagle puppies were inoculated with tissue culture fluid (control puppies, n = 8), or CAV2 (CAV2, n = 11). The puppies had clinical assessments and measurements of lung resistance (RL), and dynamic compliance (Cdyn) immediately before inoculation (Day zero) and 3 days later (Day 3). The puppies were killed on Day 3, the lungs were removed, and the right intermediate lobe was lavaged. The BALF was assessed for total and differential cell counts. Bronchiolar inflammation was quantitated by bronchiolar inflammation scores (BIS). CAV2 was localized by immunofluorescent antibody staining and electron microscopy. The control puppies remained healthy. The CAV2 puppies had positive cultures for CAV2, respiratory symptoms, and generalized necrotizing bronchiolitis. Alveolar inflammation was quantitatively less prominent than bronchiolar inflammation, and RL and Cdyn were unchanged. The BALF neutrophilia correlated with the BIS. CAV2 was present within bronchiolar epithelium, alveolar epithelial type 2 cells, neutrophils, and macrophages. CAV2 was not found in airways smooth muscles or nerves, nor in any noninflamed tissues of CAV2 puppies or in control animals. Our data suggest that acute CAV2 in beagle puppies produces an inflammation of most bronchioles. Intracellular CAV2 was found in bronchiolar epithelium, macrophages, neutrophils, and alveolar epithelial type 2 cells. Bronchiolar inflammation was reflected in BALF cytology. We conclude that bronchiolar inflammation as indicated by BIS and BALF cytology is related temporarily to histamine hyperresponsiveness in our beagle puppies.

Adenoviridae↗
PubMed1989

The use of intravenous ribavirin to treat influenza virus-associated acute myocarditis.

We studied three patients with influenza virus-associated fulminant myocarditis; one was infected by type B and the others by type A influenza virus. In one patient, dissemination of type A (H1N1) virus to the myocardium was demonstrated, and viremia complicated the clinical course despite the use of oral amantadine HCl and ribavirin aerosol. All patients were treated with iv ribavirin, two initially and the third after viremia was detected during hyperacute rejection of a cardiac transplant. No significant adverse effects could be directly attributed to therapy, and viral shedding abruptly terminated coincident with its use; however, both patients treated shortly after onset of myocarditis died. The third required support by an artificial heart, and died 8 mo later. Immunotyping of myocardial tissues in two cases revealed an initial predominance of T helper cells. Serial endomyocardial biopsies available from one of these demonstrated a subsequent marked decrease in the T helper cell population as inflammation and necrosis subsided during and following therapy.

Acute Disease↗
PubMed1989

The Tucson Children's Respiratory Study. I. Design and implementation of a prospective study of acute and chronic respiratory illness in children.

The Tucson Children's Respiratory Study, Tucson, Arizona, has been established as a long-term, longitudinal, prospective study of the risk factors for acute lower respiratory tract illnesses in early childhood and for chronic obstructive airways disease in later life. A total of 1,246 newborns were enrolled into the study between May 1980 and January 1984, representing 78% of eligible infants. Cord blood for immunologic studies, neonatal blood specimens for blood counts and differentials, and blood specimens at nine to 15 months of age for immunologic studies, blood counts, and differentials have been obtained on the majority of enrolled children. Pre-illness physiologic and more detailed immunologic studies have also been done on large subgroups of subjects. The majority of lower respiratory tract illnesses suffered by these children in the first three years of life have been assessed in detail for etiologic agents by means of culture and serologic techniques; 1,052 illnesses have been evaluated thus far. The type of illness and nature of etiologic agents are very similar to those reported in other epidemiologic studies. Thus, this group of enrolled infants and their family members constitute an appropriate population for the long-term study of risk factors for acute and chronic respiratory disorders.

Acute Disease↗
PubMed1989

The Tucson Children's Respiratory Study. II. Lower respiratory tract illness in the first year of life.

Lower respiratory tract illnesses occurring during the first year of life in 1,179 healthy infants enrolled in the Children's Respiratory Study, Tucson, Arizona, are described. The children, who use the pediatricians of a health maintenance organization, were enrolled into the study between May 1980 and January 1984. Data were collected on signs, symptoms, and diagnosis for each illness; nasopharyngeal and throat swabs were collected at the acute visit for viral, chlamydial, and mycoplasmal cultures. The cumulative incidence of illness in the first year of life was 32.88 per 100 children. Of the 348 initial lower respiratory tract illnesses occurring in these infants, 60% were diagnosed as bronchiolitis. At least one infecting agent was identified in 66% of the specimens collected at the time of the first illness. Respiratory syncytial virus was the most common isolate; 12 other agents were also identified. There was a strong (p less than 0.0001) relation between agent identified, symptoms reported, and diagnosis; bronchiolitis was predominantly associated with respiratory syncytial virus and croup with parainfluenza viruses. Sex and ethnicity were unrelated to illness experience or to characteristics of the first illness. Lower respiratory tract illness occurrence in the Children's Respiratory Study appears to be similar to patterns observed elsewhere, suggesting that diagnoses (and infecting agents) have changed little over the past decades.

Humans↗
PubMed1989

Gastrointestinal cytomegalovirus infection in heart and heart-lung transplant recipients.

Cytomegalovirus (CMV) causes major morbidity in organ transplant recipients. Gastrointestinal disease was the most prominent manifestation of CMV infection in a population of heart and heart-lung transplant patients, with an incidence of 9.9%, compared with pneumonitis (4.0%) and retinitis (0%), and occurred most frequently in CMV-seronegative recipients of organs from CMV-seropositive donors. Clinical manifestations included gastritis (nine patients), gastric ulceration (four patients), duodenitis (three patients), esophagitis (one patient), pyloric perforation (one patient), and colonic hemorrhage (one patient). Patients with gastrointestinal CMV infection were treated with intravenous ganciclovir sodium therapy, 5 mg/kg twice daily, for 2 to 8 weeks, with positive clinical, endoscopic, histologic, and virologic responses. Relapses occurred in four of nine patients who were followed up for a median period of 18 months. Retreatment resulted in healing of endoscopic lesions and in viral clearing. We conclude that early endoscopic evaluation for CMV is indicated in heart and heart-lung transplant patients with gastrointestinal symptoms. This study further suggests that intravenous ganciclovir therapy is effective for the treatment of gastrointestinal CMV in these patients.

Acyclovir↗