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Biomedical subjects

S Graham

Publications and source records attributed to S Graham.

At least 73 records · Page 4Linked to original sources

Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72-kD immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses.

CTL are held to be an important host defense mechanism in persistent herpes-virus infections. We have therefore studied the nature and specificity of human cytomegalovirus (HCMV)-specific CTL in normal persistently infected individuals. This was achieved by using vaccinia recombinants encoding viral genes expressed at different stages of the virus replicative cycle, a structural glycoprotein gB (vac.gB) and the major 72-kD immediate early nonstructural protein (vac.IE) of HCMV, combined with limiting dilution analysis of the CTL response. In two subjects, 43 and 58% of HCMV CTL precursors (CTLp) lysed vac.IE-infected cells, in contrast to less than 6% lysing gB-infected cells. HCMV-specific CTL could also be generated by secondary in vitro stimulation with vac.gB- but not vac.IE-infected autologous fibroblasts. The high frequency of 72-kD IE protein-specific CTL suggests that this is at least a major recognition element for the HCMV-specific CTL response in asymptomatic persistently infected individuals, and CTL with this specificity may be important in maintaining the normal virus/host equilibrium.

Antigens, Viral

Human cytomegalovirus-specific cytotoxic T cells: their precursor frequency and stage specificity.

Human virus-specific cytotoxic T (Tc) cells may be important in maintaining the virus/host equilibrium during persistent herpes virus infections such as that with human cytomegalovirus (HCMV). We have previously shown that HCMV-specific Tc cells are present in peripheral blood in normal asymptomatic seropositive individuals (L. K. Borysiewicz et al., Eur. J. Immunol. 1983. 13: 804). In this study we have used limiting dilution analysis to estimate the precursor frequency of these Tc cells and to further delineate their specificity for viral proteins expressed at different stages of the virus replicative cycle. HCMV-specific Tc precursor cells were present in peripheral blood lymphocytes (PBL) at a frequency of 1/5000 to 20,000 E+ PBL. This frequency was higher than that observed for varicella-zoster virus (VZV)-specific Tc cells (1/30,000 to greater than 500,000) in asymptomatic individuals and was similar to the VZV Tc precursor cell frequencies observed following clinical reactivation (1/30,000). When the stage specificity of clonally derived HCMV-specific Tc cells was analyzed, using target cells treated with phosphonoformate to allow expression of only the nonstructural viral proteins, the majority (60%) of Tc cells lysed these cells. A number of Tc cells lysed only cells which expressed the structural or late HCMV proteins. These results suggest a high precursor frequency of HCMV-specific Tc cells in PBL, and that there are subpopulations of such Tc cells specific for HCMV antigens expressed at different stages of the virus replicative cycle. However, the relative frequencies of these subpopulations suggest that the immunodominant HCMV antigens with respect to the Tc response are expressed at immediate early and/or early times.

Cells, Cultured

Infants at risk for sudden infant death syndrome (SIDS): differential prediction for three siblings of SIDS infants.

The outcome for three siblings of SIDS (SSIDS) infants was predicted, using as a risk model the sleep and respiratory characteristics of a SIDS victim studied extensively during the neonatal period. The SIDS infant had shown unstable state organization and deviant respiration patterns, including a deficit of brief apneic pauses. Like the SIDS infant, the SSIDS infants and a group of 16 normal infants were observed in the home for 7-hr periods when they were 2, 3, 4, and 5 weeks old. Two of the infants showed normal sleep and respiratory characteristics, and they were predicted to develop without respiratory dysfunction. In contrast, the third infant showed a pattern of deviancies similar to the SIDS infant; and at 4 months, she had prolonged apneic episodes, requiring resuscitation on two occasions. The findings are consistent with the notion of subtle central nervous system (CNS) dysfunction in SIDS risk infants from the time of birth.

Arousal

Zinc deficiency decreases the activity of calmodulin regulated cyclic nucleotide phosphodiesterases in vivo in selected rat tissues.

The effect of zinc deficiency on calmodulin function was investigated by assessing the in vivo activity of two calmodulin regulated enzymes, adenosine 3',5'-monophosphate (c-AMP) and guanosine 3',5'-monophosphate (c-GMP) phosphodiesterase (PDE) in several rat tissues. Enzymatic activities in brain, heart, and testis of rats fed a zinc deficient diet were compared with activities in these tissues from pair fed, zinc supplemented rats. In testis, a tissue in which zinc concentration decreased with zinc deficient diet, enzyme activities were significantly decreased over those in rats who were pair fed zinc supplemented diets. In brain and heart, tissues in which zinc concentrations did not change with either diet, enzymatic activities between the groups were not different. These results indicate that zinc deficiency influences the activity of calmodulin-regulated phosphodiesterases in vivo supporting the hypothesis that zinc plays a role in calmodulin function in vivo in zinc sensitive tissues.

3',5'-Cyclic-AMP Phosphodiesterases

Fiber type composition of the plantarflexors of giraffes (Giraffa camelopardalis) at different postnatal stages of development.

1. A sample of fibers from deep (close to the bone) and superficial (away from the bone) regions of the plantaris (PLT) and medial (MG) and lateral (LG) gastrocnemius muscles of a neonatal, a 17-day-old and an adult giraffe were typed qualitatively as dark or light based on alkaline preincubation myosin ATPase staining properties and then sized. 2. Each muscle at all ages showed a higher percentage and a larger cross-sectional area (CSA) or light ATPase fibers in the deep than the superficial region. This relationship was qualitatively, although not quantitatively, similar to that reported in hindlimb muscles of other mammals. 3. At all ages, the PLT, the deepest muscle in the synergistic group, had the highest relative total CSA of light ATPase fibers among the muscles sampled. 4. At birth, the PLT had an unusually high percentage of light ATPase fibers in comparison to that found in the same muscle of other mammals. With age, the total CSA of light ATPase fibers increased dramatically in the PLT and decreased slightly in the MG and LG. 5. These data suggest that the PLT, especially the deep portion, may functionally replace the soleus muscle which is absent in the giraffe. In addition, the fiber type results demonstrate that the changes in the fiber type composition of individual muscles observed at different postnatal ages in the giraffe are relatively similar to that reported in smaller mammals, suggesting the existence of similar regulatory mechanisms.

Age Factors

Dietary epidemiology of cancer of the colon in western New York.

The authors interviewed 428 pathologically confirmed cases of colon cancer and controls matched on age, sex, race, and neighborhood in the New York counties containing the cities of Buffalo, Niagara Falls, and Rochester. Risk of colon cancer in both males and females, studied separately, appeared to increase with the amount of total fats and total calories ingested. In addition, we found the risk to increase with increases in the Quetelet index of relative weight (weight (kg)/height (m)2). Dietary fiber was only equivocally associated with risk. Fats and Quetelet index were associated with increased risk in a regression analysis adjusting each factor for the other, as well as for fiber, age, and socioeconomic status. The same was true for calories and Quetelet index. Future efforts to clarify a possible protective role for fiber and to disentangle the effects of fats and calories need to be undertaken. The fact that calories ingested and obesity are each associated with increased risk suggests the importance of studying calorie expenditure.

Body Height

The oncogenicity of chlorambucil in rheumatoid arthritis.

Chlorambucil is useful in patients with rheumatoid arthritis (RA) refractory to other agents but there is concern about the risk of haematological malignancy with this agent. A retrospective survey was performed to assess the incidence of all types of malignancy in 39 patients treated with chlorambucil (mean daily dose 4.25 mg, mean duration of treatment 25 months). These patients were compared with 30 patients with RA who received contemporaneously, the purine analogues azathioprine or 6-mercaptopurine (mean dose 100 mg, mean duration of treatment 24 months). Eight patients treated with chlorambucil and one patient receiving purine analogues developed cutaneous malignancy (p = 0.03). In the chlorambucil-treated patients these were mostly multiple and recurrent. Three patients treated with chlorambucil developed myeloid leukaemia or a preleukaemic state, whilst no patient treated with purine analogues developed this complication. The use of chlorambucil in RA is associated with an increased risk of cutaneous as well as haematological oncogenesis.

Acute Disease

Effects of 10- to 12-day treatment with L-thyroxine in rats with myocardial infarction.

The effects of treatment with L-thyroxine (T4) for 10-12 days on left ventricular (LV) function and myosin isoenzyme content in rats with LV dysfunction after myocardial infarction were studied. Electrocardiogram (ECG) criteria were used to select animals with large myocardial infarctions. These animals were divided into six groups: control and five treatment groups that received daily subcutaneous injections of T4 (1.5, 3, 6, 10, or 15 micrograms/100 g body wt) for 10-12 days. Intravascular pressures were then measured with micromanometer-tipped catheters, and the hearts were analyzed for myosin isoenzyme distribution. The lowest dose of T4 (1.5 micrograms) produced no changes in heart rate, LV pressure or aortic pressure (AoP), myosin isoenzyme composition, or serum T4 levels. Larger doses of T4 (3, 6, 10, and 15 micrograms) produced increases in LV rate of pressure development (dP/dt), heart rate, and T4 levels but did not change LV pressure or AoP. Myosin isoenzyme composition in the control group showed increases in the proportion of the V3 form and decreases in the V1 form compared with the normal pattern. T4 administration produced dose-dependent increases in the V1 myosin isoform and corresponding decreases in the amount of the V2 and V3 forms. Heart rate increases observed with larger doses of T4 could be prevented by addition of propranolol (500 mg/l) to the drinking water. However, in rats treated with T4 and propranolol, LV pressure, AoP, LV dP/dt, and myosin isoenzyme composition were unchanged compared with T4-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The production of a macrophage-activating factor from rainbow trout Salmo gairdneri leucocytes.

Rainbow trout head kidney and blood leucocytes are shown to be capable of secreting a soluble macrophage-activating factor (MAF) after stimulation with concanavalin A (Con A). The presence of phorbol myristate acetate (PMA) as a co-stimulant increased the production of MAF. Both respiratory burst activity (nitroblue tetrazolium, NBT, reduction and H2O2 production) and bactericidal activity were enhanced after incubation of resident or elicited macrophages with the MAF-containing supernatants for 48-72 hr. The target culture period before the addition of MAF did not affect their responsiveness, but a continuous presence of MAF was necessary for maximal stimulation.

Aeromonas

A prospective randomized trial of alpha 2B-interferon/gamma-interferon or the combination in advanced metastatic renal cell carcinoma.

Eighty-nine patients with advanced measurable metastatic renal cell carcinoma were entered into a prospective randomized trial comparing alpha-interferon to gamma-interferon and to the combination. The trial was performed in order to confirm the activity of gamma-interferon and assess the potential clinical synergism. Response rates were 5, 10, and 5%, respectively. The low response rate may have been due to the inability to raise the doses of the interferons to higher levels. Clinical synergy at this dose, route, and schedule of administration in renal cell carcinoma does not exist.

Carcinoma, Renal Cell

In vivo effects of zinc deficiency on calmodulin concentrations in selected rat tissues.

Two groups of male Sprague-Dawley rats, one fed zinc-deficient diet, ad libitum, the other, pair-fed with the same diet, but given supplemental zinc in the drinking water (8 mg Zn++/ml) were studied. After ten weeks of diet, rats were exsanguinated and zinc and calmodulin concentrations in brain and testis were measured. Mean zinc concentration in testis was significantly decreased in rats fed zinc-deficient diet without supplemental Zn++, but mean zinc concentration in brain was not different. Similarly, mean calmodulin concentration in testis was decreased in rats fed zinc-deficient diet without supplemental Zn++ whereas mean calmodulin concentration in brain was not different. Distribution studies of zinc and calmodulin showed that both zinc and calmodulin were released more freely into soluble fractions of testis in rats fed zinc-deficient diet without supplemental Zn++. These results indicate, for the first time in in vivo studies, that zinc influences the calmodulin content of testis.

Animals

Detection of propionic acid vapor by rats with lesions of olfactory bulb areas associated with high 2-DG uptake.

This study tested the functional significance of recent 2-deoxyglucose (2-DG) results demonstrating a discrete focus of activity in the olfactory bulb of rats exposed to the vapor of propionic acid. Rats with lesions that destroyed this area of the olfactory bulb performed as well as did sham operated and lesioned controls in detection of amyl acetate, butanol, geraniol, propionic acid, and on a test for propionic acid threshold. Our results demonstrate that an area of the olfactory bulb containing a major focus of metabolic activity induced by exposure to an odor can be removed without producing a deficit in the detection of that odor.

Animals

Characterization of a human malignant mesothelioma cell line (H-MESO-1): a biphasic solid and ascitic tumor model.

Human malignant mesothelioma of the pleura was successfully transplanted s.c. into athymic nude mice and grew as a solid neoplastic mass. Tumor growth resulted in death of the animals between 98 and 161 days after implantation. Minced samples of the growing tumor were propagated as a malignant peritoneal effusion. Animals with malignant ascites died predictably at 32 to 33 days. Light and electron microscopy, and immunocytochemistry demonstrated a similarity of the transplanted solid and fluid malignancies with the human primary mesothelioma. Cytogenetic analysis demonstrated a predominance of cells with a triploid number of identifiable but abnormal human chromosomes. This model, which mimics the clinical behavior of malignant mesothelioma in the human, may be of value in animal trials of chemotherapy and immunotherapy.

Animals