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Biomedical subjects

G T Williams

Publications and source records attributed to G T Williams.

At least 145 records · Page 8Linked to original sources
PubMed1991

The mouse IgH 3'-enhancer.

A lymphoid-specific transcription enhancer element has recently been identified at the far 3' end of the rat immunoglobulin heavy chain (IgH) locus. Sequence analysis presented here reveals that this enhancer is flanked by a 350-bp invert repeat, giving a structure reminiscent of a transposable element. We therefore screened for the equivalent enhancer in the mouse to determine whether its presence was conserved during evolution. A mouse homologue was indeed identified and is located 16 kb downstream of the C alpha 1 exon. It is also flanked by invert repeats and these are not repeated throughout the genome. The mouse and rat enhancers retain high sequence homology. As regard activity, the IgH 3'-enhancer is lymphoid specific. However, this activity was detected in two plasmacytoma lines tested but not in two B cell lymphomas nor in HeLa cells suggesting that the enhancer may only play a stage-specific role during lymphocyte differentiation. As regards function within the IgH locus, we found that inclusion of the mouse IgH 3'-enhancer (in addition to the intron-enhancer) on mu gene expression plasmids effected a small increase in mu mRNA levels in stable plasmacytoma transfectants.

Animals↗
PubMed1991

Differentiation and limited proliferation of isolated Leishmania mexicana amastigotes at 27 degrees C.

We have demonstrated here that while many amastigotes of both Leishmania mexicana amazonensis and Leishmania mexicana mexicana differentiate to promastigotes when placed in culture at 27 degrees C, many others remain as amastigotes in their proliferative cycle. We have used this system to examine the effects of the anti-leishmanial compounds amphotericin B, 4-pentenoate and sodium stibogluconate (Pentostam) on the proliferation and differentiation of isolated extracellular amastigotes. Amphotericin B and 4-pentenoate showed little preferential effect on amastigote proliferation over promastigote proliferation although Leishmania mexicana mexicana (strain M379) was generally more resistant to these compounds than Leishmania mexicana amazonensis (strain LV78). This relative resistance was also observed in axenic cultures of proliferating promastigotes. L.m. mexicana amastigote differentiation was inhibited by amphotericin B and 4-pentenoate. Pentostam displayed a greater effect on amastigote differentiation than proliferation in both sub-species although again, a higher concentration was required to produce the same effect in L.m. mexicana.

Amphotericin B↗
PubMed1991

Gastrointestinal manifestations of type 1 neurofibromatosis (von Recklinghausen's disease).

Gastrointestinal involvement in von Recklinghausen's disease occurs in three principal forms: hyperplasia of the submucosal and myenteric nerve plexuses and mucosal ganglioneuromatosis which leads to disordered gut motility; gastrointestinal stromal tumours showing varying degrees of neural or smooth muscle differentiation; and a distinctive glandular, somatostatin-rich carcinoid of the periampullary region of the duodenum that contains psammoma bodies and which may be associated with phaeochromocytoma. This review describes the histopathological features of these lesions and discusses potential pitfalls in their differential diagnosis. Their accurate identification has significant implications for clinical management and may even provide the first pointer to the diagnosis of neurofibromatosis.

Gastrointestinal Diseases↗
PubMed1991

Smoking, humoral immunity, and ulcerative colitis.

Since ulcerative colitis predominantly affects non-smokers and ex-smokers we have examined the possibility that smoking modifies the humoral immune response to an antigenic challenge from the gut lumen. Gut lavage was used in healthy subjects and patients with ulcerative colitis, including both smokers and non-smokers. Antibodies in the intestinal fluid to Escherichia coli (five pooled serotypes), Candida albicans, gliadin, ovalbumin, and beta lactoglobulin were measured by ELISA to determine specific antibody concentrations of IgG, IgA, and IgM classes. Total IgG, IgA, and IgM were also measured in intestinal secretions and serum. In addition, circulating antibody concentrations of IgG, IgA, and IgM to three gut commensals - E coli (five pooled serotypes) C albicans, and Poroteus mirabilis were measured. There was a significant reduction in the IgA concentration in intestinal fluid of smokers with ulcerative colitis compared with healthy non-smoking controls. No other significant differences were found between the groups. Overall, these data are not consistent with the idea that smoking suppresses immune responses in the gut and suggest that the effect of smoking in colitis is mediated by another mechanism.

Adult↗
PubMed1991

Epithelial and neuroendocrine tumors of the duodenum.

This review considers the pathologic features of epithelial tumors and tumor-like lesions of the duodenum and highlights potential pitfalls in their histological diagnosis. The tumor-like lesions include Brunner's gland hamartoma, myoepithelial hamartoma, and the mucosal polyps of the Peutz-Jeghers and juvenile polyposis syndromes. The true neoplasms are of two broad groups. The first includes duodenal adenomas and carcinomas, whose microscopic features, histogenetic relationships, and clinical significance closely mimic their commoner counterparts in the large intestine and which, when multiple, are closely associated with familial adenomatous polyposis coli. The second includes a number of uncommon endocrine cell tumors showing a great diversity of histological pattern, and which may be single or multiple. Among these are typical argyrophil carcinoids, which may secrete gastrin to give rise to the Zollinger-Ellison syndrome, and which may occur as part of the inherited multiple endocrine neoplasia syndrome type 1 (MEN-1); glandular somatostatin-rich, apparently nonargyrophil, carcinoids containing psammoma bodies that can be easily confused histologically with adenocarcinomas, and which are linked to type 1 neurofibromatosis (von Recklinghausen's disease) and phaeochromocytoma; and the gangliocytic paraganglioma, a rare tumor composed of neural elements, ganglion cells, and endocrine cells. Accurate histologic diagnosis of mucosal tumors and tumor-like lesions of the duodenum is important not only for immediate patient management, but also because it may provide the first clue to the existence of an inherited tumor syndrome, with its broader implications for the patient's family and potentially important consequences for genetic counseling.

Adenocarcinoma↗
PubMed1990

Cell growth and gene rearrangement signals during the development of T lymphocytes within the thymus.

The thymus provides signals that control the proliferation and differentiation of T lymphocytes and select the repertoire of T-cell specificities. Antibodies to CD3 molecules inhibit full rearrangement of T-cell receptor beta chain genes in organ cultures of early embryo mouse thymus. Whether this effect is mediated through gamma delta CD3 expressing cells, which are present in small numbers at this stage, or through low amounts of CD3 on alpha beta precursor cells is unclear. A requirement for special gene rearrangement signals within the thymus is supported also by the observations that growth factors such as IL-2 and IL-4, although stimulating proliferation of precursor cells removed from the thymus, do not induce full T-cell receptor gene rearrangements. Recent studies show that newly formed thymic lymphocytes expressing alpha beta CD3 receptors are targets for negative selection (deletion) as a means of removing autoreactive cells. Signalling to immature thymocytes via the alpha beta CD3 complex induces the activation of endogenous endonucleases that cleave DNA into oligonucleosomal fragments. We suggest that the activation of this mechanism is the means by which autoreactive cells are removed.

Animals↗
PubMed1990

A second B cell-specific enhancer 3' of the immunoglobulin heavy-chain locus.

The expression of immunoglobulin heavy-chain (IgH) genes is generally thought to be regulated by the combination of the VH promoter with the enhancer element which is located in the JH-CH intron. This is probably an oversimplification: there are cell lines that transcribe IgH genes despite the deletion of the intron-enhancer. These findings could imply that other enhancer element(s) exist in the IgH locus. Here we show that a strong B-cell-specific enhancer is indeed located at the 3'-end of the rat IgH locus, 25 kilobases downstream of C alpha. This enhancer should be retained downstream of all rearranged IgH genes, regardless of the VH or CH segment used. Taken together with analogous findings for the mouse kappa locus, the results prompt a re-evaluation of the mechanism of regulation of immunoglobulin gene transcription. Furthermore, unlike the intron-enhancer, the IgH 3' enhancer would become linked to a c-myc that rearranges into an IgH switch region. The IgH 3' enhancer could therefore play a part in the activation of the translocated c-myc genes in rat immunocytomas, mouse plasmacytomas and Burkitt lymphomas.

Animals↗
PubMed1990

The sequence of the mu transmembrane segment determines the tissue specificity of the transport of immunoglobulin M to the cell surface.

Membrane IgM is expressed on the surface of B lymphocytes. It is not transported to the surface of transfected plasmacytoma or COS cells. Here, we show that mutation of four hydrophilic amino acids in the microm transmembrane is sufficient to overcome the intracellular retention of membrane IgM in non-B cells. This suggests that the B cell-specific IgM-associated proteins that have been postulated to assist the transport of membrane IgM to the cell surface (3) act either by forming a hydrophobic sheath that surrounds the microm transmembrane segment or by displacing an interaction with this segment that would otherwise cause retention. Experiments with a CD8/mu hybrid H chain indicate that the proteins that assist the transport of membrane IgM to the B cell surface at most need the mu CH4 and transmembrane/cytoplasmic portion for interaction.

Amino Acid Sequence↗
PubMed1990

Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis.

The survival, differentiation, proliferation and development of haemopoietic precursor cells and the functional activity of mature blood cells are all influenced by colony stimulating factors (CSFs). As haemopoietic cells rapidly die in the absence of appropriate CSF, the promotion of cell survival mediated by CSFs, or growth factors, is fundamental to all the other effects exerted by these factors. This enhancement of cell survival is distinct from the stimulation of proliferation. Here we show that the death of haemopoietic precursor cells on withdrawal of the relevant CSF. is due to active cell death, or apoptosis, indicating that CSFs promote cell survival by suppression of the process of apoptosis. The existence of a positive control mechanism regulating precursor cell survival has important implications both for the regulation of normal haemopoiesis and for tumorigenesis.

Animals↗
PubMed1990

cis-acting sequences and trans-acting factors required for constitutive expression of a microinjected HSP70 gene after the midblastula transition of Xenopus laevis embryogenesis.

Microinjected human HSP70 promoter-chloramphenical acetyl transferase (CAT) chimeric genes are constitutively expressed immediately after the midblastula transition of Xenopus embryogenesis. Analysis of a series of 5'-deletion mutants in the HSP70 promoter revealed that sequences within 74 bases of the transcriptional start site were sufficient for strong basal activity. We investigated the role of specific sequences in the basal promoter by injecting HSP70-CAT vectors containing linker-scanner mutations in the basal elements (CCAAT, purine-rich element, GC-element, ATF/AP1, and TATA). Our data reveal that deletion of any of these cis-acting elements in the basal promoter prevents expression after the midblastula stage of development. Furthermore, we have identified specific binding activities in embryonic nuclear extracts that complex with basal promoter elements (CCAAT, ATF, and GC) of the heterologous HSP70 promoter. These trans-acting factors are detectable in nuclear extracts of early blastula embryos, and their respective binding activity increases dramatically after the midblastula transition. The expression of the human HSP70 gene after the midblastula transition of Xenopus embryogenesis requires an array of cis-acting elements, which interact with specific Xenopus transcription factors.

Animals↗
PubMed1990

Silicone plastinated pathology specimens and their teaching potential.

Plastination is a process of tissue preservation by impregnation with silicone polymers or epoxy resins. The resulting specimens are dry, odourless, durable, life-like, non-hazardous, maintenance-free, and do not deteriorate with time. The technique may be easily mastered by those with a basic knowledge of histology laboratory practice. A small-scale system is relatively inexpensive to establish and specimens are comparable in cost to traditional 'pots'. Plastinated specimens are a useful adjunct to the teaching of pathology, anatomy, radiology, and surgery, and are particularly suited to use in small groups. They are much preferred to conventional 'pots' by both students and teachers owing to their accessibility, superior illustrative powers, and comparative ease of interpretation.

Attitude of Health Personnel↗
PubMed1990

Implantation of a benign rectal villous adenoma in the surgical track after transsphincteric excision. Report of a case.

A 56-year-old male patient underwent excision of a rectal villous adenoma by a transsphincteric approach. Six years after surgery, an extrarectal mucinous mass was noted, which, on biopsy, had histologic features of implantation of benign villous adenoma within the operative scar. For medical reasons, surgery was avoided and the lesion enlarged until symptoms necessitated rectal excision five years later. Histologic examination of the resected mucinous tumor supported an origin from implanted adenomatous epithelium. This is apparently the first description of implantation of an adenoma in the surgical track. Care should be taken during transsphincteric and transsacral excision of rectal adenomas to prevent implantation at the time of surgery.

Adenoma↗
PubMed1990

Tripotassium dicitrato bismuthate enemas in the treatment of ulcerative proctitis.

Eleven patients with active proctitis or proctosigmoiditis completed one month's treatment with tripotassium dicitrato bismuthate enemas administered at night. Symptoms, sigmoidoscopic appearances, and the histological grade of acute inflammation were assessed at the commencement of therapy and after one month. An overall score of these features showed improvement in 9 of 11 patients, which encourages further investigation of bismuth in controlled trials for patients with inflammatory bowel disease.

Adult↗
PubMed1990

Maximal stress-induced transcription from the human HSP70 promoter requires interactions with the basal promoter elements independent of rotational alignment.

Transcription of the human HSP70 gene is regulated by a complex array of cis-acting promoter elements that respond to conditions that include normal conditions of cell growth and induction following physiological stress. We have examined the requirements of the basal and inducible promoter elements by using promoter mutations and a transient transfection assay. Multiple forms of stress-induced transcription, including heat shock and incubation with heavy metals or amino acid analogs, are mediated by a single heat shock element (HSE) between -105 and -91 consisting of three contiguous 5-base-pair units, NGAAN, that are inverted relative to adjacent units. Maximal inducible expression requires a fully functional basal promoter. Spacing mutations which alter the relative helical orientation of adjacent genetic elements have only minimal effects on basal and stress-inducible expression and show no effects of periodicity. In addition, placement of the HSE adjacent to the basal promoter removes the requirements for a fully functional basal promoter for maximal stress-inducible expression. These results suggest that factors bound at the HSE and the basal promoter can function through multiple interactions.

Base Sequence↗