Japanese biological warfare research on humans: a case study of microbiology and ethics.
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Biological Warfare↗
Biomedical subjects
S Harris
Publications and source records attributed to S Harris.
To breed or not to breed: an analysis of the social and density-dependent constraints on the fecundity of female badgers (Meles meles).
Data from post-mortem examinations, population density estimates and long term capture-mark-recapture studies have been combined to look at the pattern of reproductive behaviour and the social factors leading to reproductive failure in badgers in Britain. The results are used to evaluate whether the hypothesis that the defence of oestrous females (as opposed to defence of food resources) best explains territorial behaviour and the social organization of badgers. Badgers in Britain have two peaks of reproductive activity, one immediately post partum and one in the summer/autumn. These coincide with two peaks of ovulation, and in the late winter/spring there is a steep rise in the number of sows carrying blastocysts, to reach an asymptote in June for yearling sows and April in older sows. Measured by their contribution to overall productivity, winter/spring matings were much more important than summer/autumn matings, contributing 65% of total autumn blastocysts in yearling sows and 71% of autumn blastocysts in older sows. The relative importance of the two mating periods is reflected in the seasonal pattern of bite wounding in adult male badgers; minor bite wounding in January-March was 2.3 times as frequent as in August-October, and moderate-extensive bite wounding was 3.1 times more frequent. In the populations studied, pre- and post-natal losses were high, with reproductive failure occurring at all stages of the breeding cycle, so that less than 30% of potential productivity was achieved. Indeed 22% of sows failed to develop blastocysts; these had a lower body mass, less body fat, larger adrenal glands, poorer health and higher bite wound scores than sows with blastocysts. Only 44% of adult sows implanted their blastocysts and proceeded to the end of pregnancy. However, it was less easy to identify features characteristic of sows that did or did not go on to implant their blastocysts. Finally, 35% of sows that produced cubs ceased lactation early, and this loss of entire litters was thought to be due to infanticide by dominant sows. The presence of annexe setts correlates with increased productivity in younger sows, and this is thought to be because annexe setts enable younger sows and their cubs to avoid the aggression of older, more dominant sows. Living in large social groups has no net reproductive gain for adult males or females, and there was a decline in productivity (per adult) with increasing group size.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Position-independent expression of the ovine beta-lactoglobulin gene in transgenic mice.
The major milk whey protein of sheep, beta-lactoglobulin (BLG), is expressed specifically in the mammary gland in a developmentally regulated pattern. To identify the cis-acting DNA regions involved in the regulation of BLG expression, resected gene constructs were analysed in transgenic mice. BLG transgenes which contain at least the proximal 406 bp of the 5' flanking region were expressed in all mice analysed, at levels related to transgene copy number, and thus were expressed in a position-independent manner. Expression was restricted to the mammary gland, except in a few lines where low-level expression was also detected in the salivary gland. In these mice, BLG transgenes were expressed during pregnancy and lactation in the appropriate temporal pattern. Further resection of the 5' proximal region to -146 bp resulted in a dramatically reduced frequency of expression, without affecting tissue specificity, while a construct which retained only 79 bp of 5' flanking region was not expressed. Chromatin analysis of isolated sheep nuclei showed that the promoter resides within a DNAaseI-hypersensitive region in the mammary gland but not in the liver. A BLG transgene displayed a similar tissue-specific pattern of DNAaseI hypersensitivity in mice. These data demonstrate an essential role of the proximal DNAaseI-hypersensitive sequences for position-independent expression of the BLG gene.
Animals↗
[Importance of examination in the choice of the right surgical method of treatment of facial paralysis].
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Biocompatible Materials↗
Rotational ablation of coronary artery lesions using single, large burrs.
Previous clinical use of the Rotablator in coronary artery disease has involved a sequential increase in burr sizes up to 2 mm in diameter and has often utilized balloon adjunct to achieve an optimal result. We report our experience and describe our technique using a single, large burr (2.25, 2.5, or 2.75 mm diameter) without balloon assistance. The burr size was selected to approximate 70-90 percent of the apparent normal lumen diameter. Thirty-one patients with 36 lesions of complex morphology (eccentric, irregular, calcified, ulcerated, at bends, at bifurcations, completely occluded, as well as balloon failures) were successfully treated with the Rotablator. Results were assessed by computerized quantitative angiography. The percent diameter stenosis (mean +/- SD) for the group was reduced from 69.8 +/- 11.3% to 30.9 +/- 10% (p less than 0.001). The mean absolute diameter stenosis increased from 0.9 +/- 0.3 mm to 2.2 +/- 0.3 mm (p less than 0.001). Angiographically visible dissections were seen in 4 patients and were uncomplicated in 2. One patient had a non-Q-wave myocardial infarction. A fourth patient had a presumed acute occlusion 36 hr after the procedure, necessitating emergency bypass surgery, but without Q waves on the electrocardiogram or wall-motion abnormalities on the echocardiogram. Nitroglycerin was infused through the Rotablator catheter and has considerably lowered the degree and frequency of spasm. No other acute complications occurred. The mean procedure time using a single burr was shorter than when multiple burrs were used: 56.5 vs. 97.3 min, respectively (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
A study of cell proliferation in formalin-fixed, wax-embedded bone marrow trephine biopsies using the monoclonal antibody PC10, reactive with proliferating cell nuclear antigen (PCNA).
We have investigated proliferation in bone marrow trephine biopsies from 32 patients with normal or abnormal haemopoiesis, using the monoclonal antibody PC10, which detects proliferating cell nuclear antigen (PCNA), together with immunohistochemical markers of haemopoietic cell lineage. PCNA immunostaining revealed the pattern of proliferation within individual haemopoietic lineages in normal marrow. Two unexpected observations were made: of erythroid cells, only pro-erythroblasts and occasional early normoblasts reacted, and positivity of megakaryocytes was unrelated to nuclear lobulation or CD61 expression. The pathological cases represented conditions in which haemopoiesis is increased (reactive hyperplasia, chronic granulocytic leukaemia, myeloproliferative and myelodysplastic syndromes, megaloblastic anaemia). Increases in the number, and disturbances of the spatial organization, of PCNA-expressing cells were present to a variable extent in all cases. Sheets of PCNA-positive megaloblastoid erythrocytes were frequently found in myelodysplastic and myeloproliferative tissue, associated with marked disturbances in the spatial organization of all haemopoietic lineages. Cases of megaloblastic anaemia due to vitamin B12/folate deficiency also demonstrated greatly increased erythroid PCNA expression, with positivity in some giant metamyelocytes. In addition to reflecting increased proliferation, elevated PCNA expression in some bone marrow pathologies may be due to altered kinetics of the protein induced by disturbances in growth factor production.
Autoantigens↗
Influence of body weight on rates of change in bone density of the spine, hip, and radius in postmenopausal women.
Interrelationships between percent of ideal body weight (%IBW), serum estrogen levels, and change in bone mineral density (delta BMD) and bone mineral content (delta BMC) were studied in 288 postmenopausal women aged 41-71 years who participated in a 2-year calcium supplement trial. The spine (L2-L4) and femoral neck were measured by dualphoton absorptiometry, and the radius was measured by single-photon absorptiometry. Years since menopause, calcium intake, and initial BMD or BMC were included as independent variables in two-phase regressions of delta BMD and delta BMD on %IBW. Increased %IBW protected against loss of spine BMD [regression slope estimate = 0.05, 95% C.I.: (0.03, 0.26)] and BMC in women up through about 106 %IBW but not in heavier women. Increased %IBW was not significantly related to delta BMD or delta BMC at the femoral neck or radius. Women above 106 %IBW had significant gains in spine and femoral neck area (P less than 0.05). Serum estrone and estradiol were positively correlated with delta BMD and delta BMC at the femoral neck only.
Absorptiometry, Photon↗
Rates of change in bone mineral density of the spine, heel, femoral neck and radius in healthy postmenopausal women.
Rates of change in bone mineral density (BMD) at four skeletal sites were measured in 288 healthy postmenopausal women (41-71 years) who were participants in a 2-year calcium supplement trial. Mean calcium intake from food and supplements was 719 +/- 299 (sd) mg/day during the study. Annualized change in spine (L2-4) BMD, adjusted for body size, dietary calcium intake, treatment group and smoking was -2.24% +/- 2.07% (sd) in women who were 1 to 2 years postmenopausal and declined in women through 5 years after menopause. The rate of change in women who were 6 or more years postmenopausal was -0.96% +/- 2.96%. Mean adjusted change in heel BMD in all women was -1.16% +/- 3.26%. At the femoral neck and radius there was no significant adjusted change in BMD in the group as a whole (femoral neck -0.24% +/- 2.55%; radius -0.14% +/- 2.24%), and the rate of bone loss was not detectably accelerated in women closest to menopause. Rates of bone loss in the subset of subjects who received no calcium supplementation tended to be greater at all skeletal sites.
Adult↗
Congenital 21-hydroxylase deficiency as a new deletion mutation. Detection in a proband during subsequent prenatal diagnosis by HLA typing and DNA analysis.
A child with 21-OH-def whose 9 weeks' pregnant mother was referred for prenatal diagnosis was found upon very careful histocompatibility testing to lack expression of any of his father's HLA antigens on his peripheral blood lymphocytes. The possibility of alternative paternity was considered to be extremely unlikely after additional genetic marker tests. The conclusion that the affected child's disease resulted from inheritance of a maternal CYP21B (21-OH) deletion and a de novo deletion in the paternal chromosome 6 segment that includes both the CYP21B (21-OH) and HLA genes was confirmed by subsequent DNA analysis using 21-OH, C4, DPB, and PCH6 probes. The presence of a heterozygous RFLP for DPB, the absence of a deletion for either CYP21B (21-OH) or C4 genes, and the presence of a paternal HLA antigen haplotype on the fetal cells additionally indicated that the fetus lacked the same deletion and could be predicted to be completely normal.
Adrenal Hyperplasia, Congenital↗
Expression of SV-40 T antigen in the small intestinal epithelium of transgenic mice results in proliferative changes in the crypt and reentry of villus-associated enterocytes into the cell cycle but has no apparent effect on cellular differentiation programs and does not cause neoplastic transformation.
The mouse intestinal epithelium represents a unique mammalian system for examining the relationship between cell division, commitment, and differentiation. Proliferation and differentiation are rapid, perpetual, and spatially well-organized processes that occur along the crypt-to-villus axis and involve clearly defined cell lineages derived from a common multipotent stem cell located near the base of each crypt. Nucleotides -1178 to +28 of the rat intestinal fatty acid binding protein gene were used to establish three pedigrees of transgenic mice that expressed SV-40 large T antigen (TAg) in epithelial cells situated in the uppermost portion of small intestinal crypts and in already committed, differentiating enterocytes as they exited these crypts and migrated up the villus. T antigen production was associated with increases in crypt cell proliferation but had no apparent effect on commitment to differentiate along enterocytic, enteroendocrine, or Paneth cell lineages. Single- and multilabel-immunocytochemical studies plus RNA blot hybridization analyses suggested that the differentiation programs of these lineages were similar in transgenic mice and their normal littermates. This included enterocytes which, based on the pattern of [3H]thymidine and 5-bromo-2'-deoxyuridine labeling and proliferating nuclear antigen expression, had reentered the cell cycle during their migration up the villus. The state of cellular differentiation and/or TAg production appeared to affect the nature of the cell cycle; analysis of the ratio of S-phase to M-phase cells (collected by metaphase arrest with vincristine) and of the intensities of labeling of nuclei by [3H]thymidine indicated that the duration of S phase was longer in differentiating, villus-associated enterocytes than in the less well-differentiated crypt epithelial cell population and that there may be a block at the G2/M boundary. Sustained increases in crypt and villus epithelial cell proliferation over a 9-mo period were not associated with the development of gut neoplasms--suggesting that tumorigenesis in the intestine may require that the initiated cell have many of the properties of the gut stem cell including functional anchorage.
Animals↗
Regional changes in body composition by time of year in healthy postmenopausal women.
We examined regional changes in fat, lean, and bone tissue for greater than 1 y in 125 postmenopausal women. Duplicate whole-body scans were performed at 6-mo intervals. Period 1 was June or July to December or January and period 2 was December or January to the following June or July. Lean and bone tissue mass in the arms, legs, trunk, and whole body increased in period 1 and decreased in period 2 [eg, lean tissue in legs increased 1.84 +/- 0.41% (mean +/- SE) in period 1 and decreased 2.84 +/- 0.39% in period 2, P less than 0.001]. In each region except the arms, fat tissue decreased in period 1 and increased in period 2. Quadriceps muscle strength was correlated with lean tissue mass of the legs [rp (controlled for height) = 0.24, P V 0.02] and physical activity was correlated with quadriceps strength. Overall, body weight did not change significantly (0.17 +/- 0.41% increase, P greater than 0.20); however, there was a net loss of 1.08 +/- 0.39% (P less than 0.01) in lean tissue in the legs and a net increase of 3.43 +/- 1.12% (P less than 0.01) in fat tissue in the trunk.
Absorptiometry, Photon↗
Limited joint mobility in subjects with insulin dependent diabetes mellitus: relationship with eye and kidney complications.
Three hundred and fifty seven subjects (178 males and 179 females) with insulin dependent diabetes mellitus were evaluated for the presence of limited joint mobility of the interphalangeal joints. Sixty six subjects (19%) had stage 1 and 26 subjects (7%) had stage 2 involvement of their interphalangeal joints. The presence of contractures was significantly related to mean longitudinal glycated haemoglobin (HbA1) concentrations, duration of diabetes, age of onset, mean longitudinal cholesterol concentrations and blood pressure. Limited joint mobility was also significantly associated with early diabetic retinopathy and raised albumin excretion rates. Limited joint mobility remained a significant factor in the logistic regression model for albuminuria and grade of retinopathy when controlled for smoking, cholesterol concentrations, duration of diabetes, age, gender, and blood pressure. However, limited joint mobility was only significantly associated with diabetic retinopathy when the effect of HbA1 concentrations was included in the multivariate model.
Adolescent↗
Nitrogenase activity and growth of Frankia in batch and continuous culture.
Frankia grown in batch culture was unable to maintain a high rate of nitrogenase activity and, once a peak level was reached, activity rapidly declined. Addition of 5 mM carbon source of cultures or transfer to fresh medium was followed by brief recovery of nitrogenase activity. The extent of recovery decreased as additions or transfers were made to progressively older cultures. Daily addition of fresh medium (dilution rate = 0.125 day-1) allowed Frankia to be maintained in continuous, derepressed culture with stable rates of growth and nitrogenase activity for more than 30 days. The proportion of active, mature vesicles also remained constant in continuous culture but decreased with time in batch culture.
Bacteria↗
Recognition of telegraphy signs at different listening levels and frequencies.
The recognition of telegraphy masked by noise at 40 and 80 signs/min telegraphy speed was studied in 10 normal-hearing subjects at different sound pressure levels (25-85 dB SPL in steps of 5 dB) as well as at different test frequencies (2000, 1000, 800, 630, 500 and 250 Hz). The ability to recognize the signs varied with varying SPL. Recognition for most of the subjects was best at an SPL close to 70 dB. All subjects improved their recognition as the frequency was lowered to 500 Hz, some even at 250 Hz. These facts should be taken into consideration when training telegraphy operators as well as in the construction of radio receivers to permit listening at low frequencies. Furthermore, the critical ratio was calculated at the different test frequencies.
Acoustics↗
The osteocutaneous free fibula flap: is the skin paddle reliable?
This clinical and anatomic study was undertaken to see if the skin paddle of the osteocutaneous fibula flap could be made more reliable. Eighty cadaver limbs were dissected to evaluate the type, number, and location of the cutaneous perforators supplying the lateral leg. Three types of perforators were identified: septocutaneous, musculocutaneous, and a type we termed septomuscular, which does not actually run within the muscle substance but is adherent to the muscle. Although not a true musculocutaneous perforator, it should be treated as such clinically. Musculocutaneous perforators were found to be more numerous and more proximal than the septocutaneous perforators. Eighteen clinical cases demonstrate a 33 percent skin paddle survival when dissected as a septocutaneous flap and a 93 percent skin paddle survival when dissected as a septomusculocutaneous flap. In using the osteocutaneous fibula flap, it is recommended that a cuff of soleus and flexor hallucis longus be incorporated into the flap to help ensure flap viability.
Bone Transplantation↗
Angiotensin-converting enzyme inhibitor therapy and diabetic retinopathy.
This pilot project suggested that angiotensin-converting enzyme (ACE) inhibitors may have an effect on delaying or reversing diabetic retinopathy. One patient who had Grade 5 (preproliferative) retinopathy improved to Grade 2 (microaneurysms only) after two years of treatment. Of the 450 patients followed in our eye and kidney clinic, no other patient showed a similar reversal from Grade 5 retinopathy without treatment. Improvement by one or more grades was seen in three other patients with variable grades of retinopathy after a mean of 3.3 years of treatment. Improvement was not related consistently to a decrease in blood pressure (0 of 4), better glycemic control (2 of 4), or reduction in albumin excretion rate (0 of 4). Proper double-blind controlled studies are needed to prove the effect of ACE inhibitors on diabetic microangiopathy of the eye.
Adolescent↗
Rabies in urban foxes (Vulpes vulpes) in Britain: the use of a spatial stochastic simulation model to examine the pattern of spread and evaluate the efficacy of different control régimes.
The threat of rabies being reintroduced into Britain is probably greater now than at any time over the last 60 years. This threat is reviewed with particular regard to the problems that would be posed should rabies be introduced to the high-density fox populations found in many cities in southern England. Computer models can provide a valuable means of understanding the pattern of rabies spread in fox populations and the likely problems of control, so the construction of previous rabies models was reviewed. None were found to be suitable for analysing the particular problems posed by high-density, spatially heterogeneous, urban fox populations. Therefore, a new spatial stochastic simulation model was produced, based on demographic and other data collected during a long-term study on the urban fox population in Bristol, and fox density data collected from a number of cities in southern England. The simulation model was used to analyse the effects of spatial heterogeneity in the fox population on the pattern of rabies spread. Simulations were then used to evaluate the effects of: (i) varying levels of fox control; (ii) changing the size of the control zone; (iii) the onset of the rabies epizooty at different times of the year: and (iv) delay before the commencement of control on the chances of containing the disease. These simulations were run for four cities (Bournemouth and Poole, Bristol, Leicester and the West Midlands conurbation) with different mean fox population densities. It was found that the variance in the monthly velocity of the rabies front was greater for heterogeneous fox populations. In cities with high fox densities, low or moderate levels of control were unsuccessful in containing the disease, but these urban areas had the highest rates of success with the highest levels of control. A three-month delay in the commencement of a rabies control campaign on average reduced the chance of successfully controlling the disease by 10-20%, although this was higher in lower-density fox populations. Rabies outbreaks in the dispersal period were on average 10% less likely to be contained. Increasing the size of the control zone increased the chances of successfully containing the disease, although this effect was density dependent, so the effect was less in low-density fox populations. These results are discussed in relation to the current rabies contingency plans for British urban areas.
Animals↗