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Biomedical subjects

M Skinner

Publications and source records attributed to M Skinner.

At least 145 records · Page 8Linked to original sources

Costochondritis: a morbid complication in a survivor of cardiopulmonary resuscitation.

Complications from closed-chest cardiopulmonary resuscitation (CPR) have been described almost exclusively on the basis of autopsy results. A survivor of CPR with clinical costochondritis resulting from resuscitation is described for the first time in the medical literature. In this case, the confounding presence of post-CPR costochondritis in a patient with documented coronary artery disease was suggested by marked local tenderness of the affected costochondral junctions. Differentiation between costochondritis and coronary artery disease was established by injection therapy of the involved costochondral joints.

Coronary Disease↗

Hemodialysis-associated amyloidosis and beta-2 microglobulin. Clinical and immunohistochemical study.

The beta-2 microglobulin type of amyloidosis was identified in articular and para-articular tissues of 14 patients with non-amyloid nephropathies undergoing long-term hemodialysis. Ten patients had carpal tunnel syndrome, 13 had juxta-articular radiolucent cysts (complicated by spontaneous fractures of the femoral neck in three), and six had destructive arthropathies of the large joints of the limbs. Massive amyloid deposits were found in the synovium, capsule, ligaments, articular cartilage, and/or bone. They were characterized by Congo red-induced green birefringence that was sensitive to potassium permanganate treatment. They reacted with anti-beta-2 microglobulin antiserum, whereas they did not react with antibodies directed against AA protein, prealbumin, or immunoglobulins. These data suggest that the potentially disabling arthropathy of hemodialysis is due to amyloid lesions. The persistently elevated plasma beta-2 microglobulin levels may play a role in the pathogenesis of this recently recognized complication, and if so, this complication should be preventable.

Aged↗

Changing clinical spectrum of splenic abscess. A multicenter study and review of the literature.

The changing demographics of splenic abscess in regard to predisposition, clinical setting, diagnosis, bacteriologic findings, and treatment have been presented based on 19 patients from five institutions and 170 patients reported in the literature since 1978. These data, in turn, have been compared with a previously published retrospective review of the world literature from 1900 to 1977. It has become clear that since 1978, splenic abscess is diagnosed earlier in its presentation due to the widespread use of improved imaging techniques, immunocompromised patients comprise a much larger proportion of patients (24 percent) than previously due to increasing use of steroids and chemotherapeutic agents, and the diagnosis of fungal splenic abscess, almost unheard of before 1978, has increased to 26 percent of patients. The diagnostic sensitivity of computerized tomography (96 percent) has clearly been shown to be superior to ultrasonography, and gallium, indium, and technetium-99m liver and spleen scanning. The diagnosis of splenic abscess, however, is still often not considered due to its rarity and the presence of predisposing conditions which obscure its clinical presentation. Untreated splenic abscess is still fatal, and although splenectomy is the mainstay of treatment, it appears that antifungal treatment without splenectomy can be recommended for patients with disseminated fungal disease as long as bacterial abscess has been ruled out by invasive culture techniques. Scattered reports of percutaneous drainage exist and are increasing in the literature, although the results are as yet inconclusive. Eventual recovery depends on early diagnosis and successful treatment of the underlying condition.

Abscess↗

Planning the archaeological recovery of evidence from recent mass graves.

Mass graves commonly contain hundreds of putrefying bodies, which bear evidence of torture and extrajudicial execution. These require careful excavation using archaeological techniques to recover the bodies for identification and to obtain associated evidence which document human rights abuses. In order to derive forensically defensible conclusions, exhumation of a mass grave may take weeks or months. Specialized protective suits and breathing apparatus will permit the investigating team to take the time required to retrieve even subtle evidence from repellent remains. Strategies for sampling tissues and bodies which reduce the magnitude of the recovery operation are described.

Archaeology↗

Further mapping of markers around the centromere of human chromosome 19.

The gene for myotonic dystrophy (DM) is located on the proximal long arm of chromosome 19 along with at least 10 cloned genes and anonymous DNA segments. In order to refine the map of this region of the chromosome, we have constructed somatic cell hybrid lines from fibroblasts carrying a balanced translocation t(1, 19) with a breakpoint at 19q12. We have established that D19S7 is the most proximal of the available long-arm markers and confirmed that PEPD localizes to 19q, along with PVS, MSK19, and MSK37. We have also examined the segregation of markers from the proximal long-arm region of chromosome 19 in hybrids containing fragments of this chromosome.

Animals↗

Pars plana vitrectomy for vitreous amyloidosis.

Thirty-six pars plana vitrectomies were performed on 30 eyes of 17 patients with biopsy-proven vitreous amyloidosis. Reopacification of the retrolental vitreous was the most common reason for vitrectomy revision, required in 24% of patients. Complications of amyloid or vitrectomy included retinal detachment requiring scleral buckling in 17% of eyes and glaucoma requiring filtering surgery in 17% of eyes. After a mean 35-month post-vitrectomy follow-up, 48% of eyes had visual acuities of 20/40 or better, and 32% of eyes had visual acuities between 20/50 and 20/100. Twenty percent of eyes had visual acuities of 20/200 or worse due either to persistent retinal detachment, open angle glaucoma, or residual opacification of the vitreous.

Amyloidosis↗

Nucleotide sequence of the gene encoding the surface projection glycoprotein of coronavirus MHV-JHM.

Sequences encoding the surface projection glycoprotein of the coronavirus, murine hepatitis virus (MHV), strain JHM, have been cloned into pAT153 using cDNA produced by priming with specific oligonucleotides on infected cell RNA. The regions of three clones pJMS1010, pJS112 and pJS92, which together encompass the surface protein gene have been sequenced by the chain termination method. The sequence of the primary translation product, deduced from the DNA sequence, predicts a polypeptide of 1,235 amino acids with a molecular weight of 136,600. This polypeptide displays the features characteristic of a group 1 membrane protein; an amino-terminal signal sequence and carboxy-terminal membrane and cytoplasmic domains. There are 21 potential glycosylation sites in the polypeptide and a cysteine-rich region in the vicinity of the transmembrane domain. During maturation proteolytic processing of the polypeptide occurs and at positions 624 to 628 the sequence Arg-Arg-Ala-Arg-Arg is found, which is similar to a number of basic sequences involved in the cleavage of enveloped RNA virus glycoproteins. The fusogenic properties of the MHV surface protein do not appear to correlate with a strongly hydrophobic region at the putative amino terminus of the carboxy-terminal cleavage product.

Amino Acid Sequence↗

Lack of amyloid in abdominal fat aspirates from patients undergoing long-term hemodialysis.

Recent reports describe the carpal tunnel syndrome (CTS) due to amyloid infiltration of the beta 2 microglobulin protein as a frequent complication of long-term hemodialysis. Carpal synovial and cystic bone lesion amyloid deposits have been reported; however, the extent of systemic amyloid deposition has not been determined. We examined 30 patients undergoing long-term hemodialysis for CTS and performed abdominal fat tissue aspiration for amyloid staining to evaluate the presence of systemic amyloid disease. In this group, CTS was frequent (37%) and its prevalence correlated with the duration of hemodialysis. In all patients, the abdominal fat tissue, stained with Congo red, was negative for amyloid deposits. These results confirm that CTS is a frequent complication of long-term hemodialysis; however, in this study, no detectable amyloid deposits were found in abdominal subcutaneous fat tissue. Thus, abdominal fat aspiration may not be a reliable screening test for hemodialysis-associated amyloidosis.

Abdomen↗

Production of an amino acid sequence-specific antiserum against human amyloid A (AA) and serum amyloid A (SAA) protein.

The hydrophilic nonapeptide Ser-Asp-Ala-Arg-Glu-Asn-Ile-Gln-Arg, identical with residues 59-67 of human amyloid protein A (AA) and serum amyloid protein A (SAA), was covalently bound via its carboxyl-terminal end to the carrier-protein keyhole limpet haemocyanin. The complex was injected subcutaneously into ten rabbits. All rabbits produced antisera which, unabsorbed, were specific for AA and SAA. The antisera and their isolated peptide specific antibodies were performance-tested and found to be excellent for demonstration of AA and SAA in immunoblotting and immunohistochemical techniques but unsuitable for immunoprecipitation. Since it is difficult to produce AA- and SAA-specific antisera by procedures earlier described and commercial supplies of good such reagents are unavailable, the easy production of sequence-specific such antisera will facilitate more extended studies of the corresponding antigens for diagnostic and scientific purposes.

Amino Acid Sequence↗

Isolation of the amyloid P component from the Engelbreth-Holm-Swarm (EHS) tumor of the mouse.

The amyloid P component was isolated from the mouse EHS tumor, a producer of basement membrane-like material. Following collagenase treatment of the tissue homogenate and centrifugation, the supernatant was purified by calcium-dependent binding to agarose, and elution with ethylenediaminetetraacetic acid. Identification of the purified material as the amyloid P component was established by immunodiffusion and electron microscopic appearance as 8.5 nm pentagonal units, frequently assembled into columns. SDS-PAGE gel electrophoresis yielded 25,000 D bands, suggesting that the amyloid P is of the mouse type. It is proposed that the mouse amyloid P component extracted from the tumor is located within the basotubules present in the pericellular matrix.

Amyloid↗

Secondary (AA) amyloidosis in cystic fibrosis. A report of three cases.

The authors report the pathologic features of three cases of amyloidosis associated with cystic fibrosis. Renal biopsy led to the diagnosis (case 1) or suspicion (case 2) of amyloidosis in patients who were 23 and 21 years old, respectively. The third patient died at age 22 years, and amyloidosis was not discovered until autopsy. Immunohistochemical staining and potassium-permanganate pretreatment of histologic sections in all three cases provided evidence that the amyloid seen in these patients is of the secondary (AA) type. Congo red staining in each case and electron microscopy in case 1 confirmed the initial diagnosis of amyloidosis. A markedly elevated serum amyloid A protein (160 micrograms/mL; normal less than 1 microgram/mL) in case 1 indicated the presence of large quantities of the precursor protein from which the AA fibrils of secondary amyloid are derived. The kidneys, spleen, and liver contained amyloid deposits in autopsy material from all three cases. Involvement of other organs by amyloid was variable. Review of autopsy material in Boston from 23 additional cystic fibrosis patients with long-term survival did not reveal any evidence of amyloidosis. It appears that secondary amyloidosis is emerging as a significant, although rare, complication of cystic fibrosis as greater numbers of these patients survive into adulthood.

Adult↗

Renal amyloidosis. Evaluation by gallium imaging.

A study has been performed to evaluate the efficacy of gallium imaging in the detection of renal amyloidosis. Ten of the 11 patients who had biopsy-proven renal amyloidosis demonstrated marked uptake in both kidneys. One patient revealed moderate gallium uptake in his kidneys. None of the patients had underlying renal or extrarenal pathology other than amyloidosis, which could account for renal gallium uptake (renal infection, neoplasm, hepatic failure or frequent blood transfusions). Four patients also had extrarenal foci of abnormal gallium uptake, suggesting other sites of amyloid deposits. Our data strongly suggest that gallium imaging has a high sensitivity for detection of renal amyloidosis. Its specificity is enhanced significantly by careful review of the clinical history to exclude other known causes of renal gallium uptake. Potentially, gallium imaging may be used to monitor the progress of patients under experimental therapy.

Adult↗

The association of an elastase with amyloid fibrils.

The fibrils of all systemic forms of amyloid (primary, AL; secondary, AA; and hereditary, AF) that had been isolated by the water extraction procedure demonstrated elastolytic enzyme activity when examined in a specific assay using tritiated elastin. The source of this fibril-bound enzyme activity was consistent with human neutrophil elastase (HNE), since it was readily extracted by high salt solutions and inhibited by an elastase-specific chloromethyl ketone inhibitor, human alpha-1-protease inhibitor or by an antibody specific for HNE. The presence of an elastase on the amyloid fibril may suggest physiologic mechanisms of amyloid precursor protein degradation.

Amyloid↗

In vitro formation of amyloid fibrils from intact beta 2-microglobulin.

Prompted by the identification of hemodialysis-associated amyloid protein as beta 2-microglobulin, we attempted to create in vitro amyloid fibrils from the native protein. Beta 2-microglobulin in PBS was slowly dialyzed free of salt and then concentrated. The residue showed Congophilia with green birefringence by light microscopy and polarization, and non-branching fibrils of indeterminate length, measuring 8 to 10 nm in diameter by electron microscopy, thus meeting the morphologic criteria for amyloid. The present study demonstrates the first successful in vitro creation of amyloid fibrils with intact precursor protein molecules and provides supporting evidence that hemodialysis-associated amyloid is constituted from beta 2-microglobulin.

Amyloid↗

Widespread occurrence of AP in amyloidotic tissues. An immunohistochemical observation.

Plasma (P)-component of amyloid (AP or SAP), while not an integral part of the amyloid fibril, has been considered to be intimately associated with virtually every different type of amyloid. In the present study, we evaluated the distribution of AP in the organs frequently involved in two forms of human systemic amyloidosis (AA and AF) and in mouse AA amyloidosis, by use of immunohistochemistry with anti-AP. Although the amyloid deposits generally showed moderate reactions with anti-AP, they were not always clearly distinguished from the surrounding non-amyloid tissue elements which often stained as well. The basement membrane often showed even stronger reaction to anti-AP than the adjacent amyloid deposits, and liver sections demonstrated such a high overall reaction to anti-AP that the anti-AP reaction on the amyloid deposits was often obscurred. The present results suggest that the binding between AP and the amyloid fibril may not be monospecific, that AP by this technique occurs rather widely throughout the body, and therefore that anti-AP may not be considered as specific a marker for amyloid deposits in immunohistochemical and perhaps other studies as well.

Amyloid↗