Measurement of Breslow depth.
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Melanoma↗
Biomedical subjects
S P Clark
Publications and source records attributed to S P Clark.
Bechet's colitis: a differential diagnosis in inflammations of the large intestine.
A previously well 39 year old woman presented with severe localized and painful anorectal ulceration. There were no other associated symptoms apart from arthritis of the hips and fingers. In the absence of definitive tissue diagnosis, a presumptive diagnosis of Crohn's disease was made. After a period of progression, the inflammation and ulceration subsided with conservative therapy. Following a relatively symptom-free period of 7 years, painful ulceration recurred in the same segment of bowel, which was refractory to steroid therapy but responded to defunctioning of the rectum. Upon excision of the defunctioned rectum, multiple discrete ulcers developed in the remaining colon, with a fistula from the distal sigmoid colon to the midline wound. The patient simultaneously developed painful apthous ulceration of the mouth and throat, and pustules appeared on the perianal skin and trunk for the first time. A colectomy was performed, with good results. The pathology of the colonic lesions is described. The characteristic appearance of these lesions, together with associated 'major' and 'minor' clinical criteria, enabled a diagnosis of Bechet's disease to be made. Although there is some overlap, particularly in the distribution of this condition with Crohn's colitis, the pathologic appearances in Bechet's colitis are relatively distinct. A diagnosis of Bechet's colitis should not be excluded in a patient presenting with atypical inflammatory bowel disease, even if associated clinical criteria are not simultaneously present.
Adult↗
The effects of comfrey derived pyrrolizidine alkaloids on rat liver.
Three groups of young adult rats were fed pyrrolizidine alkaloids derived from Russian comfrey to study the effects of the herb on the liver. Group I animals received a single dose of 200 mg/kg body wt, Group II 100 mg/kg three times a week for 3 weeks and Group III 50 mg/kg three times a week for 3 weeks. All rats showed light and electron-microscopic evidence of liver damage, the severity of which was dose dependent. There was swelling of hepatocytes and hemorrhagic necrosis of perivenular cells. There was a concomitant loss of sinusoidal lining cells with disruption of sinusoidal wall and the sinusoids were filled with cellular debris, hepatocyte organelles and red blood cells. Extravasation of red blood cells was evident. Terminal hepatic venules were narrowed by intimal proliferation, and in Group II and III, reiculin fibres radiated from these vessels. These appearances have been described in veno-occlusive disease due to pyrrolizidine alkaloids from other plant sources such as Senecio and Crotalaria. The safety of comfrey, a widely used herb, in relation to human consumption requires further investigation.
Animals↗
Properties of BGP1, a poly(dG)-binding protein from chicken erythrocytes.
The chicken beta A-globin gene contains in the neighborhood of its 5' promoter a (dG)-homopolymer sequence 16 base pairs long. The 66 kD protein BGP1 (beta globin protein 1), isolated from chicken erythrocytes, has been shown to bind specifically to this sequence. We describe further purification of BGP1, measure its affinity for the beta A-globin promoter binding site, and analyze its binding properties. The minimal binding sequence is seven dG residues; methylation interference studies show that each of these residues contacts BGP1. Binding competition experiments employing (dG).(dC) oligomers of varying lengths also consistent with (dG)7 as a minimum recognition sequence. All of the data can be explained by a model in which BGP1 binds to any contiguous set of seven (dG) residues, so that the effective constant for binding to (dG)n is proportional to n minus 6. This behavior may be typical of proteins that bind specifically to repeated sequences.
Animals↗
Testicular germ cell tumor with pineal metastases.
A patient with a mixed testicular germ cell tumor (choriocarcinoma, teratocarcinoma and embryonal carcinoma) that had metastasized to the lungs, cerebrum, and pineal gland is presented. The metastases had resulted in localized neurological signs and initially, on clinical grounds, a primary intracranial lesion could not be excluded. The occurrence of tumor metastases to the pineal gland is discussed and the literature is reviewed.
Adult↗
Suicide by band saw.
Suicidal injuries caused by power tools have rarely been reported in the literature. The case of a 37-year-old white male schizophrenic patient who sustained a fatal self-inflicted neck injury from a band saw, while engaging in occupational therapy, is presented. Unusual features of this type of injury as noted at postmortem examination were the extent of the wound, the absence of hesitation injuries, and the presence of grease wipe, bone dust, and sawdust within the wound.
Adult↗
Papillary cystadenocarcinoma of the appendiceal stump with mucocele and peritoneal metastases.
A 54-year-old Polynesian male developed a mucocele of the appendiceal stump 25 years after appendicectomy. Scattered peritoneal deposits up to 0.4 cm in diameter were also identified at laparotomy, and these were confined to the right iliac fossa. The cyst was excised with a right hemicolectomy and histology showed a mucus-producing papillary cystadenocarcinoma arising in the unburied appendiceal stump. There was invasion of the cyst wall and the peritoneal nodules contained metastatic tumour acini. The patient is well 12 months after surgery. This is a case of a rare tumour arising uniquely in an appendiceal stump and producing a mucocele. The term mucocele is discussed and recommendations made for its usage in pathological diagnosis.
Appendectomy↗
An erythrocyte-specific protein that binds to the poly(dG) region of the chicken beta-globin gene promoter.
The promoter region of the chicken adult beta-globin gene contains a sequence of 16 deoxyguanosine residues located at a nucleosome boundary in tissues where the gene is inactive. In definitive erythrocytes that express the beta-globin gene, the nucleosome is displaced, the G-string and adjacent sequences are occupied by sequence-specific DNA-binding proteins, and a nuclease hypersensitive domain is generated in this region. To gain insight into the role of the G-string in this series of events, we have examined the proteins that bind to it. Using the gel mobility shift assay and a monoclonal antibody that blocks specific binding to the G-string, we have identified a specific protein, BGP1, that is found only in chicken erythroid cells and appears at the same time, or shortly before, the changes in chromatin structure. The antibody interacts strongly with BGP1 and cross-reacts weakly with Sp1. Although both BGP1 and Sp1 require Zn2+ for their DNA-binding activity, these proteins differ in their binding-site specificities, chromatographic properties, and molecular weights. In contrast to Sp1, which is found in a wide variety of cell types, BGP1 is restricted to erythrocytes and is most abundant in definitive erythrocytes. Thus, its presence corresponds to the tissue- and stage-specific occupancy of the G-string in vivo.
Animals↗
Comparison of the transcriptional properties of the Friend and Moloney retrovirus long terminal repeats: importance of tandem duplications and of the core enhancer sequence.
The effects of sequence differences within the long terminal repeats (LTRs) of various murine retroviruses on transcription are examined by linking genetically engineered recombinant LTRs to the protein coding region of the herpes simplex virus thymidine kinase (TK) gene and assaying TK expression in tissue culture fibroblasts. The Goldberg/Hogness box region and the enhancer region are examined independently. We find that the Friend and Moloney Goldberg/Hogness boxes (TATAAAA and AATAAAA, respectively) give similar results in this assay, whereas differences between the sequences in the enhancer region have a marked effect. Tandem duplications increase the transcription level of the LTR. A single nucleotide transition in the core enhancer sequence has as large an effect on transcription as the presence of a tandem duplication: thymidine in the fifth position of the core enhancer (TCTGTGGTAAG) leads to a much higher transcriptional activity than cytidine. The LTRs have been implicated by others in the oncogenic potential of murine retroviruses, which is perhaps dependent on the transcriptional properties endowed in part by the core enhancer and tandem duplications.
Base Sequence↗
The human T cell antigen receptor is encoded by variable, diversity, and joining gene segments that rearrange to generate a complete V gene.
A cDNA clone YT35 , synthesized from poly(A)+ RNA of the human T cell tumor Molt 3, exhibits homology to the variable (V), joining (J), and constant (C) regions of immunoglobulin genes. We have isolated and sequenced the germ-line V and J gene segment counterparts to YT35 from a human cosmid library, and these failed to encode 14 nucleotides of the cDNA clone between the V and J regions. We postulate that these 14 nucleotides are encoded by a third gene segment analogous to the diversity (D) gene segments of immunoglobulin heavy chain genes. This T cell antigen receptor V gene appears to be assembled from three gene segments, V, D, and J, and accordingly most closely resembles immunoglobulin heavy chain V genes.
Amino Acid Sequence↗
Fluidity of a retrovirus genome.
Comparison of the genomic sequences of the Friend spleen focus-forming virus with other murine retroviral sequences indicated that the spleen focus-forming virus was derived from at least three retroviruses. The 5' end of the virus, from the primer binding site through most of gag, was derived from AKV. The rest of gag and all of pol were of uncertain origin, but were probably derived from the same xenotropic virus that gave rise to the 5' half of env. The remainder was derived from Friend murine leukemia virus. The positions of a 585-base deletion, a 6-base duplication, and a point insertion that leads to a frame shift and premature protein termination in the ecotropic 3' end of env were invariant between three spleen focus-forming virus strains, indicating that they had a single common ancestor. However, the point of crossover between xenotropic viral sequences and Friend murine leukemia virus was different in each strain, and two strains were much more closely related to each other than to the third in the xenotropic region, indicating that these strains had diverged by multiple recombinations. Furthermore, a different nucleotide comprised the single point insertion near the 3' end of env, suggesting that these viruses have an extremely high transition and transversion rate.
Animals↗
Complete nucleotide sequence of an infectious clone of Friend spleen focus-forming provirus: gp55 is an envelope fusion glycoprotein.
The Friend spleen focus-forming provirus is 6,296 base pairs (bp) in length. Compared to Moloney murine leukemia virus, it has undergone five major deletions, three substitutions, and a number of minor alterations. Otherwise, these viruses are about 90% homologous. A 16-bp palindrome is found in the region thought to be involved in packaging and dimerization of the RNA genome. Premature termination of translation of the gag polyprotein is attributed to a 13-bp deletion in the p12 region. A substitution of xenotropic env sequences was identified in the 5' region of the env gene; 150 nucleotides 3' to this substitution, a deletion of 585 bp removes the site where the normal env precursor protein is cleaved to form gp70 and p15(E), resulting in a fusion protein of Mr 44,725. Due to these changes, the env product gp55 is expected to have a substantially different conformation on the cell surface compared to either a xenotropic or ecotropic gp70 protein, and may be responsible for the rapid erythroleukemic potential of spleen focus-forming virus.
Amino Acid Sequence↗
Nucleotide sequences of the murine retrovirus Friend SFFVp long terminal repeats: identification of a structure with extensive dyad symmetry 5' to the TATA box.
The two long terminal repeats (LTRs) of the integrated provirus of the polycythemia strain of the Friend spleen focus forming virus have been sequenced. Each of the identical LTRs is 514 nucleotides long and together confer on the provirus the features of a transposable element. They are terminated by perfect 11 base-pair inverted repeats, and the entire provirus is flanked by an apparent duplication of host DNA four nucleotides long. The assumed transcription regulatory sequences (Hogness-Goldberg box, CAAT box, polyadenylation signal) can be identified within the LTRs, as well as a region of an imperfect inverted repeat which extends from approximately 140 to 270 nucleotides 5' from the point of transcription initiation. This sequence may form a hairpin-type structure which might have some function in the promotion of transcription.
Animals↗
Clonal analysis of early and late stages of erythroleukemia induced by molecular clones of integrated spleen focus-forming virus.
The integrated proviral DNA of the polycythemia-inducing isolate of Friend spleen focus-forming virus (SFFVp) has been identified in rat cell clones nonproductively infected with this replication-defective erythroleukemia virus and cloned in phage lambda vectors. These lambda SFFVp recombinants, lambda SFFVp502 and lambda SFFVp542, contain endonuclease EcoRI inserts of size 7.4 and 8.2 kilobases, respectively, and include full copies of the SFFVp genome, along with host flanking sequences. Infectivity of the cloned SFFVp genomes was tested by a two-step DNA transfer procedure involving transfection of the cloned DNA into 3T3 mouse fibroblasts or cotransfer of the cloned DNA into thymidine kinase-deficient 3T3 cells together with the cloned thymidine kinase gene of herpes simplex virus, followed by rescue of the transferred DNA by superinfection with a helper virus. Inoculation of the rescued virus into adult mice resulted in the appearance of spleen foci, rapid splenomegaly, and polycythemia. Early after infection, spleen cell populations contained large numbers of cells capable of forming small erythroid colonies in vitro (CFU-E) in the absence of erythropoietin. Late after infection, these mice contained cells capable of forming macroscopic colonies (CFU-FV) in vitro. These data indicate that molecular clones of SFFVp, in conjunction with a helper virus, induce the appearance of hemopoietic colony-forming cells characteristic of both the early and late stages of Friend leukemia.
Animals↗
Orientation of membrane glycoproteins in sealed rod outer segment disks.
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Animals↗
Improved optical equipment for immunofluorescence studes.
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Fluorescent Antibody Technique↗
Short-term preservation of cultures for transmission by post.
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Bacteriological Techniques↗
A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains.
We have cloned and sequenced a human mRNA specific for mammalian T-lymphoid cells. The message was found to be expressed in human and murine T lymphoblasts, thymocytes and phytohaemagglutinin-stimulated T lymphocytes. The protein deduced from the cDNA sequence has a molecular weight of 34,938 and shows extensive similarity to the entire length of the variable, joining and constant regions of mammalian immunoglobulin light chains. In addition, the relative positions of the cysteine residues are similar to those of the light chains of murine and human immunoglobulin molecules. These properties suggest that the cDNA clone may correspond to a message that specifies part of the human T-cell receptor.
Amino Acid Sequence↗