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Biomedical subjects

D J Lang

Publications and source records attributed to D J Lang.

At least 73 records · Page 4Linked to original sources

Urinary cyclic AMP and post-traumatic acute renal failure.

Consecutive daily urinary excretion of cyclic AMP has been investigated in 16 patients with severe trauma or illness, five of whom developed acute renal failure (ARF). Fluctuations in the nucleotide excretion exceeded the range found in 20 healthy volunteers (1.26-14.74, mean 7.13+/-1.18 vs. 2.04-10.10, mean 5.07+/-2.21 micronmol/24 h). This resulted in a 41% increase of cAMP excretion in the group with normal renal function (P less than 0.003) with the highest individual increase of 87%. The excretion usually reached its peak by 24 h after trauma and its lowest value by the third day, (first day vs. third day; 7.82+/-4.23 vs. 3.96+/-2.58 micronmol/24 h, P less than 0.05 for a group of 11 patients), while creatinine clearance remained normal. In four patients with severe ARF, the mean urine volume was above control value but the cAMP excretion was reduced to 3.9 to 14.4% and in one patient with a mild ARF to 60.6%. Creatinine excretion of the group was less reduced than that of cAMP (41.2% vs. 19.6%, resp.). cAMP excretion declined proportionally with diminishing creatinine clearance. In the category of 33-65 ml/min it decreased by 33.4% to 3.39 micronmol+/-1.16 micronmol/24 h. cAMP/creatinine ratio proved to be a less sensitive indicator than cAMP/24 h. Daily output of cAMP and creatinine correlated highly with diuresis in ARF patients, controls (always P less than 0.001) and less in patients with normal renal function (P less than 0.02). Urinary cAMP appears to be a very sensitive and early indicator of the onset of ARF and subsequent recovery. This warrants its further study.

Acute Kidney Injury↗

Infection and fertilization of mice after artificial insemination with a mixture of sperm and murine cytomegalovirus.

Female mice were artificially inseminated with a solution of sperm and cytomegalovirus (experimental) or sperm alone (control). Maternal infection was usually induced when virus accompanied sperm at insemination. Fertilization occurred in the presence of virus, and embryogenesis appeared normal on gross examination, although a slight reduction in the number of embryos was observed in the experimental group. Tissue cultures were prepared after gestation for 14 days from individual and pooled embryos. In one of 28 instances, virus was recovered from blind-passaged, experimental, embryonic fibroblasts. All control cultures were negative. This model may prove useful in further study of the pathogenesis of intrauterine cytomegalovirus infection.

Animals↗

Transmission and activation of cytomegalovirus with blood transfusion: a mouse model.

A mouse model that mimics many features of human cytomegalovirus (CMV) infections associated with transfusion and perfusion is described. The concept of antigenic activation of CMV was tested by infusion of blood from latently infected mice, which were found to be virus-negative by tissue culture asssay, into uninfected allogeneic and isogenic hosts. After a latent period, virus was detectable invariably in allogeneic and only rarely in isogenic recipients. Transfusions from uninfected donors into latently infected mice activated CMV in heterologous and homologous recipients. These observations should assist in definition of relevant pathogenetic principles and may explain the failure to recover CMV from healthy human blood donors in spite of predictions of a carrier state based on epidemiologic observations.

Animals↗

Early acquisition of cytomegalovirus and Epstein-Barr virus antibody in several isolated Melanesian populations.

Significant differences among diverse human populations have been found in the seroepidemiology of cytomegalovirus (CMV) and Epstein-Barr virus (EBV). The present report documents a very high rate of early acquisition of antibody to CMV and EBV among three remote populations living in the Eastern Highlands of Papua New Guinea, the Solomon Islands, and the New Hebrides, respectively. These three genetically distinct populations, living in widely different ecologies and social settings, each had the same pattern of early acquisition of infection with both viruses. It is suggested that spread of CMV and EBV is determined by patterns of interpersonal contact as well as by the prevalence of virus-shedders. The large number of handlers of each infant in these studied groups appears directly related to the early acquisition of these viruses.

Adolescent↗

Detection of latent cytomegalovirus in murine salivary and prostate explant cultures and cells.

After infection of adult mice, cytomegalovirus was detectable in salivary gland suspensions by tissue culture inoculation for up to 3 months. After these cultures had become negative, virus apparently latent in these tissues could be detected in explants of salivary and prostate glands and in cell lines derived from these explants. In some cases cycles of virus-induced cell injury and regrowth were observed. Murine cytomegalovirus plaque efficiency and morphology were evaluated in prostate and salivary gland cell cultures derived from previously infected and uninfected mice. No evidence of interference was detected, although plaques size was altered (larger) in prostate cells from previously infected mice. These studies indicate the presence of a range of suppression, latency, or effects of murine cytomegalovirus detectable after the resolution of active infection and provide methods for additional study of the establishment and activation of virus latency.

Animals↗

The effect of severe trauma on urinary cyclic AMP in children of different ages.

Under routine clinical conditions the urinary excretion of cyclic AMP was studied in 97 healthy children (3 months to 16 years old) and 65 child victims of various forms of trauma and proved to be age-dependent. The mean admission cAMP urinry levels for children of all ages were increased by 44.8% and were time dependent. In 26 injured children (3 months to 9.5 years old) the excretion increased to 12.10 +/-1.29 mumol cAMP/g creatinine as compared to 8.06 +/- 2.25 mumol cAMP/g crEAtinine (50.0%; P less than 0.01) and in 38 children (9.5-16 years) it rose to 6.43 +/- 4.12 from 4.72 mumol +/- 1.10 (36.2%; P less than 0.001). In 23 victims admitted within the first two hours after trauma the cAMP levels were elevated by 31.25% in contrast to 49.2% elevation in those admitted from 2 to 24 h after trauma. In a five-day follow-up of a group of 15 surviving patients the highest excretion of cAMP was found on the first day. It was followed by a steep decline until the values plateaued on the third day at values slightly elevated above control. Compared with the fifth day, the first day excretion expressed as mumol cAMP/24 h was enhanced by 92.3% (P less than 0.01) and as a ratio to creatinine (muol/g creatine) by 52.24% (P less than 0.05. In comparison with injured adults studied previously under analogical conditions, the cAMP excretory response to trauma in children differs in higher intensity (P less than 0.01) and in the nature of the daily pattern starting with the third day. It is pointed out that the intensity of the cAMP response to pathological stimuli may be age-dependent also in other clinical conditions.

Adolescent↗

Urinary excretion of cyclic adenosine 3',5'-monophosphate in children of different ages.

The urinary excretion of cyclic AMP was investigated in 97 healthy children, 3 months to 16 years old. When the excretion was expressed as mumol/24 h an increase with age (r = 0.693, P less than 0.001) and an increase with body weight (r = 0.700, P less than 0.001) were found to be quite similar. In relation to surface area, the average excretion for children up to 91/2 years old was 4.45 +/- 1.71 mumol/m2 in constrast with 2.22 +/- 0.66 mumol/m2 in older children (P less than 0.001). The decline appears to be associated with approaching puberty. When cAMP excretion was related to urinary creatinine, an inverse correlation with age was found (r = -0.772, P less than 0.001). In the youngest category, 3 months to 4 years old, the ratio was 9.26 +/- 1.49 mumol/g creatinine vs 4.67 +/- 1.05 mumol/g creatinine in the age group 12 to 16 years old (P less than 0.001), which compares closely with the normal adult average of 4.34 +/- 1.25 mumol/g creatinine found in our previous study. Throughout there was no evidence of sex differentiation.

Adolescent↗

Cytomegalovirus replication and the host immune response.

Cytomegalovirus (CMV) is closely associated with host cellular structures, and this has a significant impact upon the immunologic response following infection. CMV may be recovered from a variety of body secretions and fluids during acute infection, and protracted shedding may supervene in some instances. The reasons for a variable host response to CMV infection remain unclear, and the mechanisms responsible for the establishment of persistence have not been worked out. CMV persistence and latency are discussed, and some recently derived relevant data are presented. An animal model has been developed consistent with clinical observations pertaining to CMV transmission with blood. Results obtained in the course of these and other studies support the concept of immunological activation of latent CMV. The timing of CMV infection relative to an unrelated antigenic challenge is probably critical in determining the emergence of immunodepression or enhancement. Some aspects of CMV sero-diagnosis are also reviewed.

Animals↗

Time related response of urinary cyclic adenosine monophosphate to trauma.

Urinary cyclic adenosine monophosphate levels were measured in 150 patients with accidental injury of varying causes. Thirty-eight healthy adults of both sexes serving as controls excreted 2.21 to 6.85 micromoles of cyclic adenosine monomphosphate per gram of creatinine, mean 4.34 +/- 1.25. In 120 patients with trauma on admission, the excretion was increased by 15.7 per cent, p less than 0.05, and the changes showed a time related pattern. In patients admitted within the first 30, 60 and 120 minutes after trauma, the mean excretion was changed by 19, 10 and minus 2.8 per cent, respectively, and in those admitted between two and 24 hours by 30 per cent. Twelve patients with differing types of trauma showed a mean 24 hour excretion reaching its peak on the first day, 44 per cent, and declining to its nadir of 2.25 micromoles per gram of creatinine on the third day, minus 47 per cent, p less than 0.01. A second rise reached its peak on the fifth day, p less than 0.05. Thereafter, the excretion fluctuated widely with peaks significantly above and below the control range, and we were unable to correlate these changes with any specific factors. In post-traumatic acute renal failure, the nucleotide excretion fell within several hours and usually reached low values, that is, below 0.25 micromoles per 1,000 milliliters per 24 hours within one to three days. In general, the excretory pattern for cyclic adenosine monophosphate followed that of creatinine clearance, but in the diuretic phase of the recovering kidney, the cyclic adenosine monophosphate levels remained more depressed than those of creatinine. The high sensitivity of urinary cyclic adenosine monophosphate to abnormalities in renal function suggests its potential as a clinical indicator.

Acute Kidney Injury↗

Growth in agarose of human cells infected with cytomegalovirus.

After infection by human cytomegalovirus (CMV), human diploid fibroblasts could grow in agarose medium for several generations. Clones of infected cells grew for weeks, although in every case they ultimately underwent lysis owing to the cytopathic effect of the virus. Virus was inoculated at high dilution and after UV irradiation in an effort to derive cells infected with noninfectious defective particles still capable of inducing cell stimulation. Dilute or irradiated virus occasionally yielded large colonies of replicating cells, although permanent transformation was not observed. One clone derived from UV-CMV-infected cells was passaged four times before undergoing lysis. During these passages the cells exhibited alterations in morphology and orientation.

Cell Division↗