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Biomedical subjects

G Smith

Publications and source records attributed to G Smith.

At least 541 records · Page 30Linked to original sources
PubMed1990

A complex between the MHC class I homologue encoded by human cytomegalovirus and beta 2 microglobulin.

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that persists in the host and can cause severe disease in the immunocompromised individual or in the fetus. Analysis of the nucleotide sequence of the virus genome has revealed the presence of an open reading frame whose predicted translation product has homology with the heavy chain of the major histocompatibility complex (MHC) class I molecule of higher eukaryotes, and the observed sequence homology was given additional significance by the independent observation that HCMV virions can bind beta 2 microglobulin (beta 2m), the light chain of the MHC class I molecule. We expressed both the HCMV class I homologue and the human beta 2m gene in recombinant vaccinia viruses. We show that the coexpressed gene products associate, that the transport of beta 2m to the cell surface is dependent on coexpression of the class I homologue and that the viral gene product is therefore functionally related to its cellular counterpart. We observe also that, in HCMV-infected cells, no synthesis of mature cellular class I molecules occurs, while messenger RNA levels remain unaltered, and we speculate that one function of the viral homologue may be to sequester beta 2m, thus preventing the maturation of cellular class I molecules and rendering the infected cell unrecognizable by cytotoxic T cells.

Cell Line↗
PubMed1990

Hours, volume, and type of work of preregistration house officers.

OBJECTIVE: To determine the hours, volume, and type of work undertaken by preregistration house officers. DESIGN: Continuous observation of 472 hours of work performed by 12 preregistration house officers based in medical wards, using standard procedures for studying work patterns. SETTING: A teaching hospital with 340 beds assigned to general medicine and coronary care. SUBJECTS: 12 Of the 16 preregistration house officers in medicine at the hospital. MAIN OUTCOME MEASURES: The hours, volume, and type of work undertaken by preregistration house officers in February 1989, as recorded by trained observers on a one to one basis. RESULTS: The hours of duty ranged from 83 to 101 hours each week, the longest period of continuous duty being 58 hours. Each shift, house officers spent up to 25 minutes travelling between wards and an average of 85 minutes treating patients in wards that were cross covered. Between 50% and 71% of house officers' time was spent on patient oriented duties during the day; this fell to between 21% and 53% at night. Each doctor spent an average of 40 minutes filing when off duty after 6 pm. CONCLUSIONS: Established procedures for studying workload were effective in monitoring doctors' hours, providing accurate information on the volume and type of work, which is essential to resolve the problems of medical staffing. The study showed that more house officers were needed and that the cross cover system should be stopped. As a result three extra preregistration house officers were appointed.

Hospital Bed Capacity, 100 to 299↗
PubMed1990

Neonatal and adult primary B cells use the same germ-line VH and V kappa genes in their (T,G)-A-L-specific repertoire.

Although there is a nonrandom usage of VH gene families by primary B cells early in ontogeny, at issue is whether the preferential rearrangement of 3' germ-line VH genes, e.g., VH7183 and VHQ52 family genes, influences the neonatal B cell repertoire that can be expressed in response to Ag. In order to address this issue, and to determine whether neonatal B cells can use the same germ-line VH and V kappa genes as adult B cells in their primary response, we have analyzed at the molecular level the neonatal antibody response to (T,G)-A-L and compared it with the adult primary response. Among the TGB5 Id+, GT+ antibodies, which dominate the neonatal response to (T,G)-A-L, two VH gene families were used: J558 (high frequency) and 36-60 (low frequency). The majority of Id+ neonatal hybridomas used the same germ-line VH gene (H10, from the VHJ558 family), but with enormous diversity in the D region, and one of two germ-line V kappa 1 genes (V kappa 1A, V kappa 1C). These are the same germ-line V-genes used by most primary adult Id+ hybridomas, and the frequency of expression of this germ-line V-gene combination appears equivalent in the neonatal and adult primary repertoires. Therefore, it is clear from this study that as early as day 5, neonatal B cells can use the same germ-line V-genes as adult primary B cells in their Ag-specific repertoire.

Amino Acid Sequence↗
PubMed1990

Stromal influences on transformation of human mammary epithelial cells overexpressing c-myc and SV40T.

The proto-oncogene c-myc and the oncogene SV40T, both of which have been implicated in the process of cellular immortalization in vitro, have been introduced via amphotropic retroviral expression vectors into the human mammary epithelial cell (HMEC) line 184A1N4 (A1N4). Two stable cell lines were established by growth in selective medium and were found to overexpress either c-myc (A1N4-myc) or SV40T antigen (A1N4-T). Neither the A1N4, A1N4-myc, or A1N4-T cells will grow in soft agar or form tumors in nude mice. However, A1N4-T or A1N4-myc cells, but not the parental A1N4 cells, form colonies in soft agar in response to either epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), or basic fibroblast growth factor (bFGF). Like EGF and TGF alpha, bFGF is moderately mitogenic for the anchorage-dependent growth (ADG) of all three cell lines. Further, co-cultivation of A1N4-T or A1N4-myc cells with primary diploid mammary fibroblasts can also induce the anchorage-independent growth (AIG) and stimulate the ADG of A1N4-T or A1N4-myc. In addition, conditioned medium obtained from these mammary fibroblasts also stimulated the AIG of the A1N4-T and A1N4-myc cells and was found to contain immunoreactive TGF alpha and bioactive FGF. The mammary fibroblasts express specific mRNA transcripts for bFGF and acidic FGF (aFGF). These results suggest that growth factors such as TFG alpha or FGF, which may be derived from the adjacent mammary stroma, might influence in a paracrine manner the phenotypic characteristics of a population of human mammary epithelial cells toward transformation.

Agar↗
PubMed1990

A mathematical model for the evolutions of anthelmintic resistance in a direct life cycle nematode parasite.

Some of the elements required of a mathematical model for the evolution of anthelmintic resistance in strongylid nematodes are described. The model comprises a series of coupled first order differential equations and assumes the parasite has a direct life cycle with overlapping generations. The parasite-host system involved only a single host. In all the cases considered, drug resistance was assumed to be determined by two alleles at a single autosomal locus. The pretreatment allelic frequencies were maintained by heterozygote advantage involving the mortality of the free-living stages of the parasite. The model suggests that alternating anthelmintic with different modes of action may be a less effective resistance management strategy than administering the same drugs simultaneously.

Animals↗
PubMed1990

Acute hospital costs of pediatric trauma in the United States: how much and who pays?

National estimates of the numbers and expenditures associated with hospitalization due to injury among children (aged 0 to 14) were derived using data from the 1984, 1985, and 1986 National Hospital Discharge Surveys (NHDS) and the 1980 National Medical Care Utilization and Expenditures Study (NMCUES). In this report, age- and sex-specific estimates of the numbers of hospital admissions and expenditures are reported for subgroup of patients defined by external cause of the injury and by nature and severity of the injury. In 1985, over 266,000 children sustained a traumatic injury resulting in hospitalization (rate of 51 per 10,000 children). Expenditures totaled nearly $1 billion. Over 80% of the hospitalizations and two thirds of total expenditures were for minor (Maximum AIS = 1.2) trauma. Moderate (Maximum AIS = 3) and severe (Maximum AIS = 4,5) trauma accounted for 18% and 2% of admissions and 31% and 8% of expenditures, respectively. Falls ranked first in expenditures and admissions (36% of the total). Motor vehicle-related injuries accounted for 19% of trauma admissions and 24% of expenditures. Other less common causes included bicycle injuries, penetrating injuries and injuries caused by the child being hit by an object or person. An estimated 28% of the total hospital charges were paid for by public sources (15% from federal government programs, 13% from state and local programs). An additional 63% of total expenditures were paid for by private sources, with the remaining 9% considered uninsured care.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidental Falls↗
PubMed1990

Splanchnic prostanoid production: effect of hemorrhagic shock.

The effect of hemorrhagic shock on rat splanchnic prostanoid synthesis was examined in vitro. Male rats were bled to a mean pressure of 30 mm Hg for 30 min. At that time a midline laparotomy was performed and the superior mesenteric artery (SMA) was cannulated and removed in continuity with its end organ (SV + SI). The SV + SI was perfused at 3 ml/min with oxygenated Krebs-Henseleit buffer at 37 degrees C. Venous effluent (3 ml) was collected at 15, 30, 60, 90, 120, 150, and 180 min and frozen for analysis of basal prostanoid release. Levels of 6-keto-PGF1 alpha (6-keto), PGE2, thromboxane B2 (TxB2), and PGF2 alpha were analyzed by radioimmunoassay and compared in the shock (SK) and sham-operated control (SM) animals. SK 6-keto and TxB2 increased significantly at 15 min of perfusion and then decreased to a lower baseline from 60 through 120 min of perfusion. The major prostanoid released at all time periods was 6-keto (2 to 20 times higher than other prostanoids). One-way ANOVA (pooled times) showed that 6-keto significantly increased in the SK group compared to the SM group (P less than 0.02). These data suggest that the splanchnic bed attempts to compensate for hemorrhagic shock by the marked release of the endogenous vasodilator prostacyclin. Release of the other prostanoids (including TxB2) from the splanchnic bed was modest in our model.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Nuclear pore complex frequency in CA1 pyramidal cells of the aging rat.

The frequency and the diameter of nuclear pore complexes, and the nuclear perimeter, were studied in CA1 pyramidal cells of the hippocampi from 3-, 9-, 24-, and 30-month-old rats (Fischer 344). No changes with age in any of these parameters were observed. This finding is discussed in terms of varied responses of different brain areas to the effects of aging.

Aging↗
PubMed1990

The relationship between foliar injury, nitrogen metabolism, and growth parameters in ozonated soybeans.

A single 12 h ozone exposure peaking at 0.20 ppm proved phytotoxic to greenhouse-grown 'Cutler 71' soybeans at each growth stage tested from V5 to R6. Visible injury occurred within 40 h on the unifoliodate leaves and middle-aged and older trifoliolates while the younger leaves were free from toxicity symptoms. In some instances visible injury was accompanied by a decrease in chlorophyll and an increase in leaf diffusive resistance. Although nitrogen fixation was not significantly altered except at early pod formation (R3), and nitrate reductase activity was significantly reduced only if the ozone exposure occurred at the time of maximal enzyme activity (V5), nitrogen content of the leaves was reduced by ozone treatment. Shoot dry weight was not affected 40 h after ozone treatment, but root dry weight was significantly reduced. Plants grown with supplemental NO(3)(-) were more sensitive to ozone than those dependent on fixed nitrogen. At plant maturity, there was no evidence of an ozone effect on shoot, root, or seed dry weight, NO(3)(-) -grown plants showed a significant increase in growth and yield over N(2)(-) plants; but no ozone effect was observed, despite the increased foliar sensitivity. Multiple ozone exposures at growth stages V3, R1 and R3 exacerbated the effects noted with a single episode and also reduced nitrogenase activity (reflected in specific and total nodule activity) and shoot and root dry weight. At plant maturity, there was again no evidence of a significant effect of multiple ozone treatment on shoot dry weight or seed yield although root weight remained low. The results would tend to support the hypothesis that older leaves of soybean do not make a significant contribution to seed yield. Although they may be injured by ozone during the reproductive phases of growth, seed yield may not be affected if the younger O(3)-tolerant leaves remain functional.

Journal Article↗
PubMed1990

An assessment of the impact of ambient ozone on field-grown crops in New Jersey using the EDU method: part 2-soybean (Glycine max (L.) Merr.).

The yields of eleven commercially grown soybean cultivars were compared in ethylenediurea (EDU)-treated and non-treated field plots in New Brunswick, New Jersey, over a 4 year period. No statistically significant difference between treatments was found for any cultivar; the inference being ambient ozone did not adversely affect soybean yield. Succeeding field experiments supported this interpretation of the data. 'Sanilac' white bean, a legume known to be more sensitive to O(3) than soybean, was found to produce a significantly greater yield in EDU-treated than non-treated plots, unlike a companion planting of 'Williams 82' soybean which did not exhibit the differential response. The results indicated that the specific EDU protocol used in the soybean experiments is capable of detecting an ozone effect in a legume. Moreover, in a concurrent greenhouse experiment the yield of EDU-treated Sanilac white bean was not significantly different from non-treated plants in the absence of ozone pollution. In a dose-response field experiment during a year of unusually high O(3) pollution, yield of 'Williams 82' increased slightly with each EDU increment up to 500 ppm and decreased at 1000 ppm. The difference between non-treated and EDU-treated plants, however, was not statistically significant. There was no evidence to suggest that the EDU concentration (500 ppm) used in previous soybean experiments reduced seed yield. Fortuitously, the tolerance of commercially-grown soybean to ambient ozone is at least partially conditioned by the practce of not irrigating the crop. The New Jersey results are in agreement with reports from Maryland, Georgia and Tennessee in which an adverse impact of ambient O(3) was not found in soybean, but contrary to a current predictive model.

Journal Article↗
PubMed1990

The population biology of the free-living phase of Haemonchus contortus.

A deterministic model for the demography of the free-living stages of Haemonchus contortus is described. The model consists of three compartments: the pre-infective stages, comprising the eggs and first- and second-stage larvae combined; third-stage larvae in the faeces; and third-stage larvae on the pasture. The mortality (mu j) of each of these stages was a function of temperature (K, where K = (degrees Celsius + 30)/100) of the form, mu j = a j exp [alpha j K] + b j exp [-beta j K]. The minimum time to second moult (tau) and the moulting rate thereafter (sigma) were also functions of temperature (ln [1/tau] = c1 + c2[1/K], and sigma = d1 exp [d2 K] respectively). The rate at which L3 larvae migrated out of the faeces was treated as a constant (0.165/larva/day).

Animals↗
PubMed1990

Characterization of serum antibody responses to recombinant HIV-1 gp160 vaccine by enzyme immunoassay. NIAID AIDS Vaccine Clinical Trials Network.

An enzyme immunoassay (EIA) was developed to measure serum antibody responses of healthy adult volunteers vaccinated with 40 or 80 micrograms of human immunodeficiency virus type 1 (HIV-1) recombinant gp160 (rgp160) vaccine at 0, 1, 6, and 18 months. This assay, which used purified rgp160 as antigen, was compared with the Biotech/Du Pont HIV-1 Western blot and the Abbott HIV-1 EIA. Of 33 volunteers who received three doses of rgp160 vaccine, seroresponses were detected in 91% by rgp160 EIA, 97% by Western blot, and 30% by HIV-1 EIA. The level of IgG rgp160 EIA antibody (mainly IgG1) peaked after the third immunization; 64% of 33 vaccinees still had detectable antibody by 12 months. The fourth immunization induced anamnestic IgG EIA antibody in 23 of 24 vaccinees, with titers ranging from 1:200 to 1:25,600. Neutralizing antibody was not detected in postvaccination sera by microtiter syncytium formation inhibition assay. Additional testing of sera by EIA indicated that the immune response to the vaccine was directed toward epitopes on both gp120 and gp41. Seroresponses to the immunodominant epitopes on gp41 were infrequent and none were detected to the neutralization epitope in the V3 region of gp120. This highly sensitive EIA is useful for characterizing HIV-1-specific antibody responses induced by an HIV-1 gp160 subunit vaccine.

Adult↗
PubMed1990

Relationship between resonance and gas exchange during high frequency jet ventilation.

We have studied the relationship between gas exchange and mechanical frequency response during high frequency jet ventilation (HFJV) at 0.5-5.0 Hz in anaesthetized pigs. The mechanical gain curve showed a minimal "anti-resonant" response at 0.8 Hz (f1) and a maximal "resonant" response at 5.0 Hz (f2). This finding may be explained by modelling the thorax and abdomen as a system of coupled masses and compliances which undergo two different modes of forced oscillation in the frequency range studied. Gas exchange was optimal in the frequency range between the minimal and maximal responses. The tidal volumes produced were greater than anatomical deadspace, suggesting that gas transport was mainly convective in this range.

Animals↗
PubMed1990

Measurement of entrainment ratio during high frequency jet ventilation.

We have measured tidal (VT), entrained (Ve) and "blowback" (Vbb) volumes during high frequency jet ventilation (HFJV) through a Mallinckrodt Hi-Lo Jet tracheal tube in anaesthetized patients. The above volumes were calculated by digital integration of the appropriate regions of flow curves derived from a pneumotachograph placed between the bias flow tubing and the tracheal tube. At a driving pressure of 1 bar, lung minute ventilation increased with increasing ventilatory frequency, whilst tidal volumes decreased. The contribution of entrainment to tidal volume (Ve/VT) remained constant, although the volumes entrained were relatively small and varied widely from subject to subject. Blowback volumes were considerable, especially at ventilatory frequencies used clinically (1-2 Hz). We conclude that it is not possible to entrain predictable concentrations of volatile agents from the low pressure bias flow during HFJV.

Adult↗