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Biomedical subjects

D Grant

Publications and source records attributed to D Grant.

At least 163 records · Page 9Linked to original sources

Amniotic fluid zinc and pregnancy outcome.

OBJECTIVE: To examine for an association between amniotic fluid zinc and pregnancy outcome. DESIGN: A prospective study. SETTING: Southmead Hospital, Bristol, UK. SUBJECTS: 191 amniotic fluid samples from 11 centers in the Southwest of England, obtained at 16-20 weeks gestation. METHOD: Samples of amniotic fluid (AF) sent for prenatal diagnosis were collected from the laboratory and analysed for zinc level. Data were then collected at a later date concerning pregnancy outcome. OUTCOME MEASURE: Antenatal complications as well as events in labour, and in particular birth weight and congenital malformations. RESULTS: 182 cases with complete data showed a mean AF zinc level (+/- S.E.) of 1.39 (+/- 0.11). There was no relation between AF zinc and antepartum haemorrhage, pregnancy-induced hypertension, post-partum haemorrhage or time and mode of delivery. Neither was there an association with birth weight. As there were no cases with major malformations, particularly of the central nervous system, possible association could not be ascertained. CONCLUSION: The study failed to demonstrate any association between AF zinc and abnormal pregnancy outcome. A modified prospective study is suggested to explore this further.

Adult↗

Development of a mouse intestinal transplantation model.

We have recently developed a mouse intestinal transplantation model. The proximal segment of donor jejunum is transplanted into the recipient in a heterotopic position. End-to-side anastomoses are performed between donor aorta and recipient aorta and between donor portal vein and recipient inferior vena cava. Mortality rates were initially high due to shock, arterial thrombosis, and postoperative sepsis. Refinements in surgical techniques reduced these complications, resulting in a high rate of success. Important technical factors included (1) minimizing ischemic injuries to the graft in both the donor and the recipient, (2) using an aortic patch and elliptical aortotomy for anastomosis, (3) administering large volumes of crystalloid to maintain normal blood pressure during the donor and recipient surgeries, and (4) using broad-spectrum antibiotics as postoperative prophylaxis. The mice with isografts had normal intestinal function and histology when they were sacrificed 1 month after surgery. This new model of small bowel transplantation will be a useful tool to study the immunology of intestinal grafting at the molecular level.

Anastomosis, Surgical↗

Nephrotoxicity in rats following liver transplantation from cadmium-exposed rats.

Although kidney is considered as the critical organ for cadmium (Cd) toxicity, little is known about the transport of Cd to kidney after chronic exposure. In order to study this transfer, male Lewis rats (150-200 g) were given eight injections (sc) of CdCl2 (3 mg Cd/kg) over 2 weeks which resulted in increases of tissue Cd and metallothionein (MT) concentrations (223 and 1850 micrograms/g, respectively, in the liver and 118 and 873 micrograms/g, respectively, in the kidney). Livers from Cd-injected rats were transplanted to age-matched control healthy Lewis rats and the recipient rats were killed at 2 to 47 days after transplantation. The levels of Cd and MT in the liver of recipient rats were decreased (106 and 1503 micrograms/g, respectively) with time after surgery. On the other hand, renal Cd and MT levels were markedly increased (195 and 1468 micrograms/g, respectively) and most of the Cd in the kidney was bound to MT. About 100 ng/ml of Cd and MT were detected in the plasma of recipient rats by ELISA. There was some periportal fibrosis in the liver due to transplant procedure which did not anastomose hepatic arteries. There was an increase in blood urea nitrogen levels in rats transplanted with Cd-containing liver. In addition, both necrosis and inflammation were observed in the epithelial cells in the proximal tubules in the kidney which typically occurs in chronic Cd toxicity. These results suggest that the major source of renal Cd in chronic Cd exposure may be derived from hepatic Cd which is transported in the form of Cd-MT in blood plasma.

Animals↗

The protein core of the NCA-related pancreatic adenocarcinoma-associated antigen (DD9-Ag) is NCA-50.

Earlier studies with monoclonal antibody (mcAb) DD9E7 have identified a family of nonspecific cross-reacting antigen (NCA)-related antigens that are highly expressed in human pancreatic adenocarcinoma. To analyse the molecular nature of these glycoproteins further, a lambda gt11 expression library has been constructed from the GER pancreatic adenocarcinoma cell line and screened with an NCA sequence-specific oligonucleotide probe. Sequence analysis and restriction enzyme mapping of the clones isolated have shown that they are all homologous with the NCA-50 protein core sequence rather than other related members of the carcinoembryonic antigen/NCA gene family. With use of the same probe, a 2.5-kb mRNA transcript, characteristic of NCA-50, was found in pancreatic adenocarcinoma tumour samples. This study suggests that the 80- to 115-kDa glycoproteins, which we had previously identified in pancreatic adenocarcinomas with NCA-specific mcAb DD9E7, are the result of aberrant glycosylation of the NCA-50 protein core following cell transformation.

Adenocarcinoma↗

The effect of donor-recipient strain combination on rejection and graft-versus-host disease after small bowel/liver transplantation in the rat.

The initial clinical experience with simultaneous small bowel/liver transplantation (SBL) suggests that liver grafting may protect the small bowel from rejection. A pilot study of SBL in DA (RT1a) rats with Lewis (RT1l) allografts in our laboratory provided experimental support for this concept. However, the clinical applicability of the data was questioned because the transplants were performed in a low-immune-responder rat strain combination. This study examined the outcome of SBL in several rat strain combinations. Isolated small bowel transplants (SB) and SBL were performed in three groups: DA-->PVG (low immune responder), BN-->LEW (intermediate immune responder) and ACI-->LEW (high immune responder). Lewis-->Lewis isografts were used as controls. All of the rats with SB rejected their allografts, whereas all of the rats with simultaneous liver grafts had minimal or no signs of intestinal rejection. The outcome of SBL was profoundly affected by the donor-recipient strain combination. The low immune responders developed severe graft-versus-host disease. The intermediate immune responders developed mild-to-moderate GVHD and moderate liver rejection. The high immune responders developed severe liver rejection. In this study, the outcome of small bowel transplantation depended upon the strain combination used and whether or not a simultaneous liver graft was transplanted. The immune interactions that occur after multi-visceral transplantation are complex and cannot be easily predicted.

Animals↗

Deletion analysis maps ocular albinism proximal to the steroid sulphatase locus.

We describe a pedigree in which four male members are affected by a contiguous gene abnormality involving the short arm of the X chromosome (Xp22.32). Bivariate flow cytometry of lymphoblastoid cell lines from two of these individuals and a normal male showed a 6-7 megabase deletion in affected males, and high resolution chromosomal G-banding of an obligate heterozygote showed the deletion to reside in the Xp22.32 region. Affected members had X-linked ichthyosis due to steroid sulphatase deficiency, Kallmann's syndrome, but no ocular albinism. In two out of four affected individuals studied, there was unilateral renal agenesis. Deletion analysis using the Xp22.32 markers MIC2, DXS31, DXS 89, GMGX9, DXS278, DXS143, and DXS9 showed that the deletion extended from DXS31 to DXS143 (inclusive). The absence of ocular albinism in this pedigree shows conclusively that the X-linked ocular albinism gene resides proximal to the DXS143 locus. Further, the inconstant association of unilateral renal agenesis with X-linked Kallmann's syndrome, even when the latter is caused by a complete deletion of the gene, suggests that the absence of the X-linked Kallmann gene can be compensated in renal development.

Albinism, Ocular↗

Deletion 9p and sex reversal.

We report a case of a female infant with a de novo deletion of the short arm of chromosome 9, sex reversal, and an apparently intact SRY gene. Sex reversal has been reported in a number of subjects with a normal Y chromosome and a deletion of the terminal segment of the short arm of chromosome 9. The factors controlling early development of the male testes are unknown. There are likely to be many genes involved and we present additional evidence that one of these is situated on the end of the short arm of chromosome 9.

Base Sequence↗

Primary lymphoma of the gallbladder.

A case of primary lymphoma of the gallbladder is described which is rare in the medical literature. A 76 year old man presented with acute cholecystitis and septicaemia. Investigation showed a lung abscess and a gallbladder mass. The mass was thought to be an empyema and cholecystostomy was performed. Biopsy of the gallbladder wall showed high-grade B cell lymphoma. The patient unfortunately succumbed to overwhelming septicaemia in the postoperative period. Postmortem examination confirmed primary lymphoma of the gallbladder without dissemination.

Acute Disease↗