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S Jacobsen

Publications and source records attributed to S Jacobsen.

At least 19 recordsLinked to original sources

The cytokine response of circulating peripheral blood mononuclear cells is changed after intravenous injection of lipopolysaccharide in cattle.

The aim of the study was to investigate lipopolysaccharide (LPS)-induced short and long term changes in capacity for intracellular cytokine-production of bovine circulating peripheral blood mononuclear cells (PBMCs). Eight dairy cows each received three intravenous injections of Escherichia coli LPS (10, 100 and 1000ng/kg, consecutively) at 3week intervals. Intracellular cytokine production was determined by flow cytometry in PBMCs obtained 0, 2, 6 and 24h after each LPS challenge. After LPS administration, proportions of monocytes producing tumour necrosis factor (TNF) alpha, interleukin (IL)-1beta and IL-8, as well as proportions of circulating lymphocytes producing interferon (IFN) gamma, decreased significantly. Within 24h, proportions had returned to or increased above pre-injection levels. Proportions of lymphocytes producing IL-4 and IL-10 increased significantly after injection of 1000ng LPS/kg. This study demonstrated that cytokine profiles shift quickly, but temporarily, to favour the anti-inflammatory response immediately after LPS exposure. The long term response to LPS was opposite to the immediate response, as cytokine profiles shifted in the 3weeks between challenges towards a pro-inflammatory response. Proportions of monocytes producing IL-1beta and TNFalpha determined immediately before the second and/or third LPS injection were higher than proportions determined before the first injection, whereas pre-injection proportions of lymphocytes producing IL-4 decreased with each challenge. These changes may result in a quicker host response to invading pathogens.

Animals↗

Overlapping humoral autoimmunity links rheumatic fever and the antiphospholipid syndrome.

OBJECTIVE: Rheumatic fever (RF) and the antiphospholipid syndrome (APS) are autoimmune diseases that share similar cardiac and neurological pathologies. We assessed the presence of shared epitopes between M protein, N-acetyl-beta-D-glucosamine (GlcNAc) and beta2 glycoprotein-I (beta2GPI), the pathogenic molecules engaged in these autoimmune conditions. METHODS: Sera from the APS patients were affinity-purified on beta2GPI and beta2GPI-related peptide columns. Sera from RF patients were affinity-purified on protein G column. The beta2GPI and M protein-related peptides were prepared by conventional solid-phase peptide synthesis. The enzyme-linked immunosorbent assay direct binding and inhibition studies were performed on the RF and APS sera for the presence, and cross-reactivity, of antibodies against beta2GPI, beta2GPI-related peptides, streptococcal M protein, M-derived peptides and GlcNAc. RESULTS: Antibodies (Abs) to beta2GPI were found in 24.4% of 90 RF patients. Antibodies against various beta2GPI-related peptides were found in 1.1-36.7% of the patients. The immunoglobulin G sera from RF patients possessed significant anti-beta2GPI activity, while sera from APS patients contained a considerable anti-streptococcal M protein as well as anti-GlcNAc activity. Furthermore, affinity-purified anti-beta2GPI and anti-beta2GPI-related peptide Abs from APS patients cross-reacted with streptococcal M protein and M5 peptide, while beta2GPI and beta2GPI-related peptides inhibited anti-streptococcal M protein activity from RF patients. The results were confirmed by immunoblot analyses. The beta2GPI also inhibited anti-GlcNAc activity from APS patients with chorea. CONCLUSIONS: The results of our study, showing a considerable overlap of humoral immunity in RF and APS, support a hypothesis that common pathogenic mechanisms underlie the development of cardiac valve lesions and Central Nervous System abnormalities in both diseases.

Acetylglucosamine↗

Osteoarthritis of the first carpometacarpal joint: a study of radiology and clinical epidemiology. Results from the Copenhagen Osteoarthritis Study.

BACKGROUND: The radiological and epidemiological data from the Copenhagen Osteoarthritis Study (COS) were analysed in order to assess the prevalence of osteoarthritis (OA) of the first carpometacarpal joint (CMCJ). Another aim of the study was to analyse relationships between radiologic CMCJ OA and self-reported pain. The third aim was to analyse if additional information could be obtained applying a new method of correlating individual radiological features to self-reported pain, compared to Kellgren and Lawrence's (K-L's) radiologic OA classification. METHODS: Between 1992 and 1994 standardised radiographs of both hands were recorded in 3,355 participants of the COS cohort. Subjects with known rheumatoid arthritis, other inflammatory arthritis or earlier fractures of the hand were excluded. OA of the CMCJ was assessed according to K-L's radiologic classification by two senior radiologists at our institution. The radiologists further evaluated individual radiologic features of CMCJ OA as recommended by K-L according to the text attached to each picture in their radiologic atlas of OA. To estimate inter- and intraobserver reproducibility a subset of 100 radiographs was reread. RESULTS: Our analyses demonstrated that the K-L method was not able to classify all X-rays. In 608 (18.1%) cases, combinations of joint space width (JSW) measurements, the graduation of osteofytes, sclerosis and cysts fell outside the classification. The radiological evaluation of individual features of OA demonstrated an acceptable reproducibility, intrapersonal (kappa=0.79) as well as interpersonal (kappa=0.65). The prevalence of each radiological feature increased after the fifth decade, progressively more so among women (P<0.001), with the highest prevalence (36.0%) of grades 3 and 4 JSW reduction among women>80 years. A significant correlation was found between signs of radiologic degeneration and self-reported pain (P<0.001); however, different combinations of OA features had different relations to symptoms. Logistic regression analyses revealed sclerosis to have an independent influence on pain in the thumb compared with the presence of osteofytes, cysts and diminished JSW. Body mass index (BMI) was positively related to radiological changes. In logistic regression analyses BMI did not demonstrate an independent positive relation to OA. CONCLUSION: Radiological degenerative changes in the CMCJ by age especially among women are quite common. However, it is demonstrated that global radiologic classifications of OA of the CMCJ have serious limitations in epidemiological studies. Not all cases fit into classification based on the K-L-atlas. Among the radiological features, subchondral sclerosis is significantly related to self-reported pain. Specific radiologic data should be incorporated in epidemiological studies on hand OA.

Age Distribution↗

Evaluation of a commercially available human serum amyloid A (SAA) turbidometric immunoassay for determination of equine SAA concentrations.

The aim of the present study was to evaluate whether equine serum amyloid A (SAA) concentrations could be measured reliably with a turbidometric immunoassay (TIA) developed for use with human serum. Intra- and inter-assay imprecision were evaluated by multiple measurements on equine serum pools. Assay inaccuracy was determined by linearity under dilution. The assay was subsequently used for measuring SAA concentrations in clinically healthy horses, horses with inflammatory diseases, horses with non-inflammatory diseases, and in horses before and after castration. In pools with low, intermediate and high SAA concentrations, the intra-assay imprecisions were 24.4%, 1.6% and 2.1%, and the inter-assay imprecisions were 33.2%, 4.6% and 6.5%. Slight signs of inaccuracy were observed, but these inaccuracies were negligible when considering the large dynamic range of the SAA response. The assay was able to detect the expected difference in SAA levels in different groups of horses. It was also able to demonstrate the expected dynamic changes in SAA after castration. In conclusion, equine SAA concentrations can be measured reliably using the TIA designed for human SAA.

Animals↗

Kinetics of local and systemic isoforms of serum amyloid A in bovine mastitic milk.

The aim of the present study was to characterise the serum amyloid A (SAA) response to intramammary inoculation of Escherichia coli and to examine the distribution of hepatically and extrahepatically produced SAA isoforms in plasma and milk from cows with mastitis. Milk and plasma SAA concentrations were determined before and after experimental induction of E. coli mastitis in six dairy cows. The milk SAA response was characterised by low or undetectable levels before inoculation, very rapid and large increases in concentration after inoculation, and rapid decline towards baseline levels after resolution of disease. In plasma from cows with experimentally induced E. coli mastitis, four hepatically derived SAA isoforms with apparent isoelectric point (pI) values of 5.8, 6.2, 6.8 and 7.4 were demonstrated by denaturing isoelectric focusing. In milk three highly alkaline isoforms with apparent pI values above 9.3 appeared 12 h post-inoculation. These isoforms were not present in any of the plasma samples, and it therefore seems likely that they were locally produced, tissue-specific isoforms. At 24-36 h post-inoculation one or more acidic isoforms corresponding to those found in plasma appeared in the milk samples. The isoforms demonstrated in plasma from cows with E. coli mastitis were also present in serum obtained from three cows with clinical Streptococcus uberis mastitis. In conclusion, experimentally induced E. coli mastitis is accompanied by a prominent SAA response. The results of the present study indicate that SAA accumulation in mastitic milk is the result of both local synthesis of SAA and of hepatically derived SAA gaining access to the milk due to increased permeability of the blood-milk barrier.

Animals↗

Optimised, low cost, low field dedicated extremity MRI is highly specific and sensitive for synovitis and bone erosions in rheumatoid arthritis wrist and finger joints: comparison with conventional high field MRI and radiography.

OBJECTIVE: To evaluate a low field dedicated extremity MRI unit for detection of bone erosions, synovitis, and bone marrow oedema in wrist and metacarpophalangeal (MCP) joints, with a high field MRI unit as the standard reference. METHODS: In 37 patients with RA and 28 healthy controls MRI of the wrist and 2nd-5th MCP joints was performed on a low field MRI unit (0.2 T Esaote Artoscan) and a high field MRI unit (1.0 T Siemens Impact) on 2 subsequent days. MRI was performed and evaluated according to OMERACT recommendations. Additionally, conventional x ray, clinical, and biochemical examinations were performed. In an initial low field MRI "sequence selection phase", based on a subset of 10 patients and 10 controls, sequences for comparison with high field MRI were selected. RESULTS: With high field, spin echo MRI considered as the reference method, the sensitivity, specificity, and accuracy of low field 3D gradient echo MRI for erosions were 94%, 93%, 94%, while the corresponding values for x ray examination were 33%, 98%, and 83%. Sensitivity, specificity, and accuracy of low field MRI for synovitis were 90%, 96%, and 94%, and for bone marrow oedema 39%, 99%, and 95%. Intraclass correlation coefficients between low field and high field scores were 0.936 (p<0.005) for bone erosions and 0.923 (p<0.05) for synovitis. CONCLUSION: Low field MRI provides high accuracy for detection and grading of erosions and synovitis, with high field MRI as the standard reference. For bone marrow oedema, specificity is high, but sensitivity only moderate. Low cost, patient compliant, low field dedicated extremity MRI provides similar information on bone erosions and synovitis as expensive high field MRI units.

Adult↗

Absence of high-affinity calreticulin autoantibodies in patients with systemic rheumatic diseases and coeliac disease.

Calreticulin has been reported to be an autoantigen in various autoimmune connective tissue diseases and in coeliac disease. Previous studies have used incubation buffers with low salt and low detergent concentrations (low stringency conditions) with serum albumin or other proteins as a blocking agent. Using these conditions we found a relatively high level of non-specific binding in many sera. Antibodies to proteins that are used as blocking reagents in ELISA (bovine serum albumin (BSA), ovalbumin, skimmed milk powder) are frequently present in sera, and these may cause false-positive results. Moreover, the low isoelectric point of calreticulin and its chaperone properties may give rise to false-positive results under low stringency conditions. We report that the use of a simple buffer without protein (50 mM Tris, pH 7.5, 1% Tween 20, 0.3 M NaCl) removes most of the problems with unwanted binding (high stringency conditions). Using the high stringency conditions, we screened sera from 107 patients with systemic lupus erythematosus, sera from patients with other systemic autoimmune diseases and from children with coeliac disease for the presence of high-affinity calreticulin autoantibodies by immunoblotting and ELISA. None of the sera contained high-affinity calreticulin antibodies. It is concluded that calreticulin is not a common autoantigen in patients with autoimmune connective tissue diseases or coeliac disease.

Autoantibodies↗

Joint space width in dysplasia of the hip: a case-control study of 81 adults followed for ten years.

In a longitudinal case-control study, we followed 81 subjects with dysplasia of the hip and 136 control subjects without dysplasia for ten years assessing radiological evidence of degeneration of the hip at admission and follow-up. There were no cases of subluxation in the group with dysplasia. Neither subjects with dysplasia nor controls had radiological signs of ongoing degenerative disease at admission. The primary radiological discriminator of degeneration of the hip was a change in the minimum joint space width over time. There were no significant differences between these with dysplasia and controls in regard to age, body mass index or occupational exposure to daily repeated lifting at admission. We found no significant differences in the reduction of the joint space width at follow-up between subjects with dysplasia and the control subjects nor in self-reported pain in the hip. The association of subluxation and/or associated acetabular labral tears with dysplasia of the hip may be a conditional factor for the development of premature osteoarthritis in mildly to moderately dysplastic hips.

Adult↗

Use of serum amyloid A and other acute phase reactants to monitor the inflammatory response after castration in horses: a field study.

REASONS FOR PERFORMING THE STUDY: Early recognition of excessive inflammation and infectious complications after surgery, leading to early institution of therapy, reduces post operative discomfort and facilitates recovery. Because serum amyloid A (SAA) is a highly sensitive marker of inflammation, measurements of SAA and other acute phase reactants in the equine surgical patient may be valuable in assisting clinical assessment of post operative inflammation. OBJECTIVES: To investigate changes in inflammatory markers after castration and to correlate levels of acute phase reactants with clinical severity of inflammation after castration. METHODS: Leucocyte numbers and blood levels of iron, SAA and fibrinogen were determined before castration and on Days 3 and 8 post operatively in 2 groups of horses; Group 1 (n = 11) had mild post operative inflammation and an uncomplicated recovery and Group 2 (n = 7) had local clinical signs of moderate to severe inflammation. RESULTS: Both groups had elevated serum SAA levels at Day 3 post operatively. In Group 1 concentrations had returned to preoperative levels by Day 8, whereas in Group 2 concentrations remained elevated. Plasma fibrinogen concentrations in serum increased to equal levels in both groups and stayed elevated throughout the study period. Serum iron concentrations of Group 1 did not change in response to castration, whereas concentrations in Group 2 decreased below preoperative levels on Day 8. Leucocyte numbers remained unchanged during the post operative period in both groups. CONCLUSIONS: Serum SAA and iron profiles reflected the course of inflammation and their levels correlated with the clinical severity of inflammation. In contrast, fever and changes in leucocyte numbers, which are usually considered to be hallmarks of inflammation and infection, were not useful for monitoring post operative recovery. POTENTIAL RELEVANCE: Measurements of SAA and iron may improve post operative monitoring. As sustained inflammation may indicate that the surgical wound has become infected, SAA and iron measurements may facilitate early recognition and hence early treatment of infection.

Acute-Phase Proteins↗

Hip dysplasia: a significant risk factor for the development of hip osteoarthritis. A cross-sectional survey.

OBJECTIVES: The aim of this cross-sectional survey of 2232 women and 1336 men (age range 20-91 yr) was to investigate individual risk factors for hip joint osteoarthritis (OA). METHODS: Standardized, weight-bearing pelvic radiographs were evaluated. Radiological hip joint OA was defined as minimum joint space width (JSW) </=2.0 mm. Hip dysplasia was evaluated according to common radiographic indices. Radiographic findings were correlated to general health and lifestyle information obtained at baseline examinations and questionnaires. The study focused on age; self-reported hip pain, occupational exposure to repeated daily lifting, body mass index, smoking and hip dysplasia. RESULTS: Hip dysplasia (HD) prevalence ranged from 5.4-12.8% depending on the radiographic index applied. Hip OA prevalence was 1.0-2.5% in subjects <60 yr of age and 4.4-5.3% in subjects >/=60 yr of age. Of factors entered into logistic regression analyses, only age (P<0.001 for right hips and P<0.001 for left hips) and hip dysplasia (P<0.001 for right hips and P = 0.004 for left hips) were significantly associated with hip OA prevalence in women. In men, only hip dysplasia was associated with hip OA prevalence, P<0.001 in right hips and P = 0.001 in left hips. CONCLUSIONS: Of the individual risk factors investigated in this study, only age and hip dysplasia were associated with the development of hip osteoarthritis.

Adult↗

Acute phase protein concentrations in serum and milk from healthy cows, cows with clinical mastitis and cows with extramammary inflammatory conditions.

The concentrations of the two acute phase proteins, serum amyloid A and haptoglobin, in serum and milk were compared in 10 cows with clinical mastitis, 11 cows with extramammary inflammatory conditions and 10 clinically healthy control cows. The concentrations of both acute phase proteins were higher in the serum and milk of the cows with mastitis than in the cows in the other two groups. Four of the cows with extramammary inflammatory conditions had serum amyloid A concentrations in serum above 100 microg/ml, but negligible concentrations in milk, indicating that a pathogen must be present in the mammary gland for serum amyloid A to accumulate in milk. The acute phase protein concentrations in milk increased significantly with increasing somatic cell count, suggesting that they may be indicators of the severity of an infection.

Animals↗

Factors influencing hip joint space in asymptomatic subjects. A survey of 4151 subjects of the Copenhagen City Heart Study: the Osteoarthritis Substudy.

OBJECTIVE: The aims of the study were to investigate the distribution of hip joint space width (JSW) in asymptomatic subjects without radiologic evidence of degeneration, and investigate the influence of age, sex, physical parameters, occupational activity, and smoking on JSW. MATERIALS AND METHODS: The distribution of minimum JSW was determined in hip joints in standardized, weight-bearing pelvic radiographs of the Copenhagen City Heart Study: The Osteoarthritis Substudy cohort of 4151 subjects. Asymptomatic subjects without radiologic osteoarthritis were included (1018M/1554F). Occupational exposure to repeated daily lifting, smoking, and physical parameters were registered for each individual. RESULTS: Overall, female minimum JSW was significantly smaller compared with male JSW (P < 0.0001). Female minimum JSW decreased significantly with age (P < 0.0001), while male minimum JSW remained relatively unaltered throughout life (P(right) = 0319, P(left) = 0.18). Minimum JSW correlated positively with height, weight, and BMI, as did femoral head radius. Multiple logistic regression analysis revealed significant influence of sex and age on minimum JSW in females only. Positive or adverse effects of cigarette smoking on hip JSW were not documented. Type and duration of occupational exposure to repeated daily lifting did not affect hip JSW significantly. CONCLUSION: Minimum JSW decreased progressively with age in women, while it was unaltered in men. A history of smoking or different occupational exposure to repeated daily lifting did not influence minimum hip JSW significantly. Differences in body mass index, height or weight did not significantly influence minimum hip joint JSW.

Adult↗

How common is attention-deficit/hyperactivity disorder? Towards resolution of the controversy: results from a population-based study.

Attention-deficit/hyperactivity disorder (AD/HD) is a common behavioral disorder among children, yet there is uncertainty about many aspects of AD/HD, including its precise frequency of occurrence, presence of comorbid conditions, long-term outcomes and the impact of treatment on long-term outcome. The objectives of the studies described in this paper were to address these important questions about AD/HD. The study subjects were from a population-based birth cohort, and included all children born in Rochester, Minnesota, from 1976 to 1982, who remained in the community after the age of 5 y (n = 5718). Complete medical and school records were available for all members of the birth cohort, including detailed information about AD/HD symptoms, psychometric test and questionnaire results, medical and non-medical treatments, and long-term academic and psychosocial outcomes. This information was used to identify 375 subjects from the birth cohort with AD/HD, based on well-defined research criteria. The estimated cumulative incidence of AD/HD at the age of 19y was 7.5% (95% confidence interval 6.5-8.4). Data from these 375 subjects with AD/HD will be used in ongoing studies of this disorder.

Adolescent↗

Dose dependency and individual variability of the lipopolysaccharide-induced bovine acute phase protein response.

In order to investigate the dose dependency and the individual variability of the lipopolysaccharide (LPS)-induced acute phase protein response in cattle, 8 nonlactating, nonpregnant Danish Holstein cows were challenged 3 times each by intravenous injection of increasing doses (10, 100, and 1000 ng/kg, consecutively) of Escherichia coli LPS with 3-wk intervals. All 3 LPS doses resulted in a rapid increase in serum concentrations of haptoglobin and serum amyloid A (SAA) and a decrease in serum concentrations of albumin in all 8 cows. Serum concentrations of acute phase proteins (APP) remained altered for several days after each LPS injection, and their increase or decrease was significantly related to LPS dose. In addition to dose dependency, the response was also dependent on the individual, as APP concentrations differed significantly among cows. To compare APP production in 2 consecutive challenges, individual APP levels after the challenge with 100 ng LPS/kg were correlated to levels attained after the challenge with 1000 ng LPS/kg. Serum amyloid A concentrations correlated between the 2 challenges, whereas haptoglobin concentrations tended to correlate; no correlation could be demonstrated between SAA and haptoglobin concentrations in either of the challenges, which suggests that the synthesis of haptoglobin and SAA are regulated in different ways. In conclusion, cattle are highly susceptible to LPS, as very low doses of LPS elicited acute phase albumin, SAA, and haptoglobin responses. Concentrations of APP not only reflect the magnitude of LPS exposure but are also influenced by the ability of the individual cow to mount an acute phase response. The ability to produce SAA and haptoglobin may be an innate characteristic of the individual, as responses in consecutive challenges were quantitatively similar.

Acute-Phase Proteins↗

Identification of monoclonal antibodies that cross-react with cytokines from different animal species.

Eleven monoclonal antibodies specific for ovine, bovine and human cytokines were investigated by flow cytometry for cross-reactivities with cytokines produced by peripheral blood mononuclear cells (PBMCs) from sheep, cattle, goat, swine, horse, dog, mink, rabbit and human. Four antibodies specific for IL-4, IL-8, IFN-gamma and TNF-alpha cross-reacted with cytokines from a majority of the species investigated. These antibodies can be applied to flow cytometric studies of cytokine production by PBMCs from several veterinary species. Another five antibodies specific for IL-2, IL-6, GM-CSF and IFN-gamma (two antibodies) cross-reacted weakly and with a variable number of animal species. These antibodies could in certain situations be useful in flow cytometry. In a number of cases the immunological cross-reactivities were confirmed by Western blot analyses. Overall, the results of this study will remedy some of the lack of species-specific anti-cytokine antibodies in veterinary research.

Animals↗

The concept of using multifrequency energy transmission to reduce hot spots during deep-body hyperthermia.

We propose a multifrequency energy transmission scheme for annular phased arrays in deep-body hyperthermia. The problem of frequency dependent resonance effects reported in hyperthermia phantom calibration studies, leading to skewed energy deposition patterns and unwanted energy maxima (hot spots), is addressed by comparing broadband energy transmission with conventional monofrequency excitation. A heating system, including microstrip spiral applicators placed at a cylindrical surface in four quadrants, was designed to study this new concept in a homogeneous phantom. The system includes an option to select three cw tones for simultaneous transmission within a frequency range from 232 to 936 MHz. Quantitative analyzes of E-field probe-scan data, generated in a 6 g/L saline phantom and evaluated by three figures of merits defined, demonstrate the possibility of adding up power in the focus site while smearing secondary maxima outside this volume. Random selection of the three sinusoids within this band shows a probability of 0.7 to improve performance compared to the conventional single-frequency heating. A numerical study of the electromagnetic problem was also implemented using the FD-TD method. Analysis shows acceptable agreement between measured and simulated two-dimensional energy deposition patterns.

Computer Simulation↗

Microsatellite stability in human post-mortem tissues.

Human identification and forensic criminal casework may involve DNA profiling of decomposed material. Somatic microsatellite (STR) instability may lead to false exclusions and theoretically to false inclusions, both in criminal cases and in human identification. Hence, the somatic and postmortal stability of the actual sequences is crucial to the reliability of such analyses. Somatic STR stability in human tissues has been documented in small series only and the effect of postmortal tissue decomposition on microsatellite stability remains to be elucidated. On this basis, we have systematically searched for somatic STR mutations in 26 deceased humans without signs of decomposition at autopsy and 25 autopsy cases with obvious signs of postmortal decomposition. A blood sample and six tissue samples were collected from each case. Seven STRs were chosen for study, the tetranucleotides HUMVWA31/A, HUMTH01, HUMF13A1, and HUMFES/FPS, and the hyperpolymorphic markers HUMAPOAI1, D11S554 and HUMACTBP2. Denaturing gel electrophoresis was performed on an ABD Prism 377 gene sequencer with Genescan 672 software (Applied Biosystems, Inc.). The bone DNA profile of each case was chosen as the standard DNA profile. All cases gave profiles from additional tissues. By intraindividual comparison of DNA profiles in the cases without signs of degradation we find that the short repetitive sequences under study are stable, that is without evidence of somatic mutations. The cases with varying degree of decomposition display postmortal microsatellite stability, we detect no somatic mutations or other possible postmortal changes that could lead to between-organ non-matches. In conclusion, PCR-based STR analyses are suitable in human identification and forensic casework dealing with different tissues, even when the substrate is heavily decomposed.

Autopsy↗