Search PubMed⌕ Search

Biomedical subjects

C E Lawrence

Publications and source records attributed to C E Lawrence.

At least 19 recordsLinked to original sources
PubMed1992

Lymphosarcoma in experimentally induced feline immunodeficiency virus infection [corrected].

A cat experimentally infected with feline immunodeficiency virus (FIV) but known to be free of feline leukaemia virus (FeLV) developed lymphosarcoma. The lesions in the liver and kidneys were present nine months after infection, when the cat was 21 months old. The cat had no overt signs of immunodeficiency and it is suggested that the B cell activation induced shortly after FIV infection produced a large pool of proliferating lymphocytes from which the malignant cells emerged.

Animals↗
PubMed1992

Clinical and pathological findings in feline immunodeficiency virus experimental infection.

A study is described of the clinical and pathological findings in 20 specific pathogen free cats infected when 1 year old with feline immunodeficiency virus and monitored over 12 months. Cats were divided into two groups (A and B). The clinical and clinicopathological features were studied in Group A. In Group B, at 1, 2, 4, 9 and 12 months post infection two cats were necropsied. Clinically all cats developed generalised lymphadenopathy, six cats were neutropenic and five cats lymphopenic. Three cats became febrile with conjunctivitis and anterior uveitis and one of these cats ultimately developed jaundice. Postmortem examinations confirmed a generalised lymphadenopathy involving peripheral and visceral lymph nodes with concurrent stimulation of splenic white matter and mucosal lymphoid tissue of the digestive tract and conjunctiva. Within the lymph nodes there was a reactive follicular hyperplasia accompanied by a paracortical hyperplasia with an increased paracortical vascularity. Unusual features were the presence of lymphoid follicles in the bone marrow, thymus and parathyroid tissue. In addition, aggregates of lymphoid cells were found within salivary glands, kidneys, sclera and choroid of the eye. One cat developed a lymphosarcoma affecting the liver and kidneys at 36 weeks post infection. The cat with jaundice had a cholangitis with marked biliary epithelial hyperplasia.

Animals↗
PubMed1992

Decreased mitogen responsiveness and elevated tumor necrosis factor production in cats shortly after feline immunodeficiency virus infection.

We present the results of an investigation into the effects of feline immunodeficiency virus (FIV) infection on the response to mitogens and cytokine production in the first month of infection. We were able to demonstrate a depression of response of peripheral blood mononuclear cells to the mitogens concanavalin A, phytohaemagglutinin and pokeweed mitogen, with the response to pokeweed mitogen being most severely affected. The response of the cells of the spleen were affected by 10 days post infection and these could not be augmented by the addition of exogenous interleukin-2 (IL-2). The response of mesenteric lymph node cells was not affected until 20 days post infection and this could be partially restored by the addition of exogenous IL-2. IL-2 production was unaffected in peripheral blood mononuclear cells, slightly depressed in mesenteric lymph node cells and slightly elevated in spleen cells. Tumor necrosis factor levels were significantly elevated with respect to controls within 10 days of infection. These studies suggest that there are a number of changes in the immune response of FIV infected cats early in infection and this may determine the subsequent outcome of the infection.

Animals↗
PubMed1991

The frequency of ion-pair substructures in proteins is quantitatively related to electrostatic potential: a statistical model for nonbonded interactions.

A statistical analysis of ion pairs in protein crystal structures shows that their abundance with respect to uncharged controls is accurately predicted by a Boltzmann-like function of electrostatic potential. It appears that the mechanisms of protein folding and/or evolution combine to produce a "thermal" distribution of local nonbonded interactions, as has been suggested by statistical-mechanical theories. Using this relationship, we develop a maximum likelihood methodology for estimation of apparent energetic parameters from the data base of known structures, and we derive electrostatic potential functions that lead to optimal agreement of observed and predicted ion-pair frequencies. These are similar to potentials of mean force derived from electrostatic theory, but departure from Coulombic behavior is less than has been suggested.

Biological Evolution↗
PubMed1991

Modelling length bias in a longitudinally-linked record system of HIV cases.

We compare numbers of hospital admissions for intravenous drug using (IVDU) HIV patients and other HIV patients in acute-care facilities in New York State. Data consist of routinely collected hospital-discharge reports from New York's Statewide Planning and Research Cooperative System, linked into longitudinal case histories. Because recognition of an IVDU depends on an opioid diagnosis on any record in the case history, the observed distribution of the number of admissions per case for recognized IVDU's is biased towards greater numbers of admissions. We develop and apply a model to overcome this biasing. Our findings reveal that the mean numbers of admissions for the two groups differ significantly, but less so than without recognition of the length biasing.

Bias↗
PubMed1991

Estimating serum polychlorinated biphenyl levels in highly exposed workers: an empirical model.

A regression model estimating high-homolog polychlorinated biphenyl (PCB) serum concentration on the basis of job exposure categorizations was developed. The model assumes first-order kinetics with a half-life determined empirically and uses variables that incorporate both intensity and duration of exposure over a 30-yr period. In order to compare the efficiency of these regression-based exposure estimates relative to often-used epidemiological parameters, models with dichotomized, ordinal, and continuous exposure surrogates were also investigated. Among the alternative exposure categorizations the most straightforward measure, ever versus never direct, was a particularly poor predictor of serum PCB level (r2 = .01). Nearly all of the candidate exposure measures we tried predicted serum levels poorly. The best of these after the fact was with total months employed in direct-exposure jobs (r2 = .43). None of the logical deductive models approached the predictability of the empirical model developed here (r2 = .69).

Adult↗
PubMed1990

An expectation maximization (EM) algorithm for the identification and characterization of common sites in unaligned biopolymer sequences.

Statistical methodology for the identification and characterization of protein binding sites in a set of unaligned DNA fragments is presented. Each sequence must contain at least one common site. No alignment of the sites is required. Instead, the uncertainty in the location of the sites is handled by employing the missing information principle to develop an "expectation maximization" (EM) algorithm. This approach allows for the simultaneous identification of the sites and characterization of the binding motifs. The reliability of the algorithm increases with the number of fragments, but the computations increase only linearly. The method is illustrated with an example, using known cyclic adenosine monophosphate receptor protein (CRP) binding sites. The final motif is utilized in a search for undiscovered CRP binding sites.

Algorithms↗
PubMed1990

Immunogenetic correlates of susceptibility to infection with Heligmosomoides polygyrus in outbred mice.

Outbred MF1 mice were characterized with respect to their susceptibility to infection with Heligmosomoides polygyrus (Nematoda) on the basis of faecal egg counts after 8 weeks of repeated infection (50 larvae/week). Selective breeding for resistance and susceptibility was carried out over 3 generations. The H-2 type of a sample of the mice was determined, and antigen recognition assessed on the basis of Western blots against adult and larval H. polygyrus homogenate. The selective breeding programme yielded very strong evidence for the heritability of susceptibility to infection. The results were consistent with a model of single gene control with resistance dominant over susceptibility. The presence of the H-2k haplotype was significantly associated with susceptibility, as was the recognition of a 17 kDa antigen in blots against both larval and adult worm homogenate. The proportion of mice phenotypically susceptible to infection, the proportion bearing the H-2k haplotype, and the proportion recognizing the 17 kDa antigen, were all approximately 0.25.

Animals↗
PubMed1990

Identification of the most significant amphipathic helix with application to HIV and MHV envelope proteins.

Amphipathic helices, which play important roles in protein structure, occur in a wide variety of lengths. Yet existing methods employ fixed window lengths. We present a hierarchical procedure that identifies the Q most significant amphipathic helices regardless of length. Since the observed hydrophobicities are not normally distributed, test statistics usually employed for least-squares regression are inappropriate for assessing statistical significance of amphipathic helices. We show that an adjusted F statistic provides a good test. An application to the envelope protein of HIV finds an unexpected long amphipathic helix in gp41.

Algorithms↗
PubMed1990

AIDS behind bars. Epidemiology of New York State prison inmate cases, 1980-1988.

During the last five years, AIDS has become the preeminent health care problem in New York State correctional facilities. Through December 31, 1988, 915 cases of AIDS had been diagnosed among inmates. This represented approximately 1% of the cumulative AIDS cases in the United States, 4% of those in New York State, and 40% of those reported in state correctional systems nationwide. An analysis of epidemiologic data on these cases showed an annual increase in cases from 3 in 1981 to 227 in 1988, with an incidence greater than 400 per 100,000 inmates per year over the past four years. While most cases occurred in males (96%), females had the same high incidence rates (compared to the general population, in which female rates are one-eight of males). Forty-seven percent of infected inmates were Hispanic, 38% black, and 13% white. Pneumocystis carinii pneumonia was the most common diagnosis (65%), while Kaposi's sarcoma was rare (3%). Previous intravenous drug use has been the major risk factor, seen in 95% of cases. A comparison of 54 inmate AIDS cases with 107 matched and 196 unmatched controls showed that inmates in whom AIDS developed had significantly lower white blood cell counts on entry into prison, lower hematocrits and serum albumin levels, and higher serum glutamic oxaloacetic transaminase and globulin counts. Through July 1989, 643 (70%) of these 915 inmates had died of AIDS, and HIV infection and AIDS account for 68% of recent inmate deaths.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Algorithms for the optimal identification of segment neighborhoods.

Two algorithms for the efficient identification of segment neighborhoods are presented. A segment neighborhood is a set of contiguous residues that share common features. Two procedures are developed to efficiently find estimates for the parameters of the model that describe these features and for the residues that define the boundaries of each segment neighborhood. The algorithms can accept nearly any model of segment neighborhood, and can be applied with a broad class of best fit functions including least squares and maximum likelihood. The algorithms successively identify the most important features of the sequence. The application of one of these methods to the haemagglutinin protein of influenza virus reveals a possible mechanism for conformational change through the finding of a break in a strong heptad repeat structure.

Algorithms↗
PubMed1989

The degradation of collagen in pig synovium in vitro and the effect of colchicine.

Colchicine induced a rapid destruction of the collagenous matrix of pig synovial explants in culture in the presence of serum. The most efficacious doses were 0.01-0.1 micrograms/ml (2.5 x 10(-8) M - 2.5 x 10(-7) M). The histological progression of the tissue breakdown induced by colchicine was very similar, although faster, to that described for other agents (Fell et al., 1986), with cells having basophilic nuclei accumulating in areas of fibril degradation. The loss of collagen correlated with an increase in collagenase production and at the peak of resorption (6 to 8 days) active collagenase was present in the culture media. Immunocytochemical methods demonstrated active collagenase bound to collagen fibrils after only 4 days in culture, before significant collagen degradation could be observed histologically. Collagen breakdown was completely inhibited by cortisol, and partially inhibited by indomethacin: only the inhibition by indomethacin could be reversed by exogenous prostaglandin E2. Vinblastine at a higher dose was as effective as colchicine but the lumicolchicines, which do not disrupt microtubules, were ineffective. Although the precise mechanism of action of colchicine is unknown, this culture system provides a useful in vitro model for increasing our understanding of the cellular mechanisms of tissue breakdown and for elucidating the roles of active collagenase and related metalloproteinases.

Animals↗
PubMed1989

The relation of polychlorinated biphenyls to birth weight and gestational age in the offspring of occupationally exposed mothers.

The authors studied the relation of polychlorinated biphenyls (PCBs) to birth weight and gestational age among the live offspring of women occupationally exposed to PCBs during the manufacture of capacitors in Upstate New York. Interviews were conducted in 1982 with 200 women who had held jobs with direct exposure and 205 women who had never held a direct-exposure job in order to ascertain information on reproductive history and other factors influencing reproductive outcome. Exposure was assessed as high-homolog PCB (Aroclor 1254), a continuous exposure variable estimated from an independently derived prediction model. After adjustment for variables other than gestational age known to influence birth weight, a significant effect of high-homolog exposure is seen for birth weight (slope of the regression beta = -33 g/unit change in natural logarithm (In) estimated serum PCB; 90% confidence interval (CI) -59 to -7; p(1) = 0.02). For gestational age, a small but significant decrease is also observed with an increase in estimated exposure (beta = -1.1 days/unit change in In estimated serum PCB; 90% CI -2.0 to -0.1; p(1) = 0.03). When gestational age is accounted for in addition to other variables related to birth weight, estimated serum PCB is no longer a significant predictor of birth weight (beta = -24 g/unit change in In estimated serum PCB; 90% CI -49 to 2; p(1) = 0.06). The authors conclude that these data indicate that there is a significant relation between increased estimated serum PCB level and decreased birth weight and gestational age, and that the decrease in birth weight is at least partially related to shortened gestational age. The magnitude of these effects was quite small compared with those of other known determinants of gestational age and birth weight, and the biologic importance of these effects is likely to be negligible except among already low birth weight or short gestation infants.

Birth Weight↗
PubMed1988

Incubation periods for paediatric AIDS patients.

A recent seroprevalence study of newborns indicates that one in 62 children born in New York City has antibodies to the human immunodeficiency virus (HIV). The distribution of incubation periods for paediatric patients is needed to estimate future AIDS case loads from these seroprevalence data. Current estimates of incubation periods for paediatric patients are based on limited data. We use parametric and non-parametric methods to analyse incubation periods for 215 paediatric patients with AIDS whose only known route of infection is maternal. We conclude that incubation periods are longer than previously reported; that there is a distinct knee in the incubation period distribution at seven months which suggests two risk populations; and that there is an increase in incidence which is consistent with exponential growth.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Effects of reagent and instrument on prothrombin times, activated partial thromboplastin times and patient/control ratios.

Activated partial thromboplastin times accumulated from two proficiency testing surveys were analyzed to determine simultaneously the effects of the method and reagent used. Prothrombin time results were reevaluated concomitantly for comparison. A robust two-way analysis of variance was applied to determine the effect of method and reagent on APTT results. The effect of the reagent and method on the ratio of abnormal to normal plasma clotting times was determined. We found a substantial difference in ratios for the PT using different reagents on the same instrument. There was an even larger effect of reagents on APTT ratios. Our finding of substantial reagent effects for the PT and APTT clearly support the need for standardization. We found standardization to be feasible only for the PT, and only if applied in a form consistent with the inherent error structure of the data. For the APTT, the present methodology and plasma samples did not achieve consistent standardization.

Blood Coagulation Tests↗
PubMed1986

Cortisol succinate is slowly hydrolysed in organ cultures of porcine articular tissues and is not equivalent to cortisol.

The pro-drug cortisol succinate is frequently used as a substitute for cortisol in organ cultures. We found, however, that in Dulbecco's modified Eagle's medium the time taken for the ester to undergo 50 per cent hydrolysis (t1/2) to cortisol was 75 h. When 15 per cent heat-inactivated normal rabbit serum was present t1/2 decreased to 47 h, but the rate of hydrolysis was not further increased in the presence of porcine articular cartilage or minced synovial tissue. When frozen and thawed synovium was present t1/2 decreased to 33 h, presumably due to the release of carboxyl-esterases from the disrupted cells. The level of tetrahydrocortisol was low in all of the cultures. The slow hydrolysis of cortisol succinate resulted in the exposure of the tissues to undesirable fluctuations in the concentration of active hormone, which decreased to low levels at each medium change. Thus, in co-cultures of porcine synovium and articular cartilage, cortisol had a greater inhibitory effect than cortisol succinate on the breakdown of cartilage matrix caused by synovial tissue.

Animals↗