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Biomedical subjects

M Chapman

Publications and source records attributed to M Chapman.

At least 73 records · Page 4Linked to original sources
PubMed1994

BCL-2 expression in human colorectal adenomas and carcinomas.

As BCL-2 oncoprotein has been implicated as a survival factor in a number of tissues, we examined colorectal tumour specimens and cell lines for BCL-2 expression. BCL-2 protein was expressed in 19/22 adenocarcinomas and 12/13 adenomas. 6/9 carcinoma cell lines and 7/8 adenoma cell lines were also BCL-2 positive. BCL-2 expression was retained in metastases to the regional lymph nodes (3/3 specimens) and in the cell line SW620, derived from a lymph node metastasis. These studies suggest a role for BCL-2 in promoting cell survival of benign and malignant colorectal tumours and that BCL-2 deregulation may be a relatively early event in colorectal carcinogenesis. The retention of BCL-2 expression in the carcinomas and lymph node metastases may explain the resistance of colorectal tumours to chemotherapeutic treatment.

3T3 Cells↗
PubMed1993

The plasma ACTH, AVP, CRH and catecholamine responses to conventional and laparoscopic cholecystectomy.

OBJECTIVES: We compared the responses of the stress hormones, cortisol, ACTH, vasopressin (AVP), corticotrophin releasing hormone (CRH) and catecholamines to elective conventional and laparoscopic cholecystectomy. DESIGN: A right upper quadrant transverse incision was used for conventional cholecystectomy, and four 1-2-cm incisions for the laparoscopic procedure (for insertion of surgical instruments, diathermy, fibreoptic telescope and light source, and carbon dioxide insufflation). Blood was sampled immediately prior to premedication (temazepam), after induction of anaesthesia (fentanyl and thiopentone) and at 10-minute intervals until the end of the procedure (N2O maintenance, vecuronium relaxation). A blood sample was taken after reversal, and then at 10-minute intervals for 50 minutes. Plasma sodium and blood pressure were measured at similar intervals. Results are expressed as mean +/- standard error. PATIENTS: Twelve patients were studied (six in each group). MEASUREMENTS: Peptide hormones were measured by radioimmunoassay, cortisol by ELISA and catecholamines by HPLC. RESULTS: The mean premedication hormone values for the conventional and laparoscopic procedures did not increase significantly after induction of anaesthesia. Within 10 minutes of the first incision, however, there was a marked concordant rise in mean plasma ACTH and AVP levels for both procedures (conventional: ACTH, from a premedication value of 10.2 +/- 1.7 to 80.1 +/- 14.3 pmol/l, AVP from 1.2 +/- 0.4 to 117 +/- 24 pmol/l, P < 0.01 for both hormones; laparoscopic: ACTH from 5.8 +/- 2.6 to 55.1 +/- 26.0 pmol/l, AVP from 1.6 +/- 0.11 to 49.2 +/- 27.09 pmol/l). At the end of both types of operation mean levels of ACTH and AVP were still elevated, although the ACTH: AVP ratio had increased. Greater variability in ACTH and AVP responses was seen in the laparoscopic than in the conventional procedure, three patients showing a relatively small response to surgery. Total secretion of ACTH during both types of surgery was not significantly less both during (P < 0.05), and after (P < 0.01) laparoscopic surgery. For both procedures, the timing of AVP and ACTH peaks was significantly related (P < 0.002). A small but significant rise in CRH was observed 30 minutes after the start of surgery for both procedures P < 0.05). The timing of CRH and ACTH peaks was unrelated. The maximum mean plasma cortisol level for the conventional procedure (1268 +/- 147 nmol/l) was reached 20 minutes after reversal of anaesthesia and remained at this level until the end of sampling. The cortisol response was comparable during the laparoscopic procedure but was beginning to fall at 60 minutes post-operatively. Plasma adrenaline responses to the two types of surgery were not significantly different, but the plasma total noradrenaline response to laparoscopic surgery as indicated by the response area during the first 20 minutes was significantly increased (P < 0.02). Plasma sodium, renin activity and initial systolic blood pressure fall were not significantly different during the two procedures. CONCLUSIONS: For both procedures, the peak of ACTH secretion after incision is likely to be AVP dependent, and the timing of peak levels of these two hormones was significantly related. Subsequent ACTH secretion may be the result of an interaction between AVP and CRH. Laparoscopic cholecystectomy results in a smaller AVP rise than does the conventional procedure, and plasma AVP falls more rapidly post-operatively. During the period of observation, ACTH, CRH, cortisol and adrenaline responses were not significantly lessened by the laparoscopic approach, but there was a significant increase in the noradrenaline response. Stress hormone monitoring may assist further improvements in surgical technique.

Adrenocorticotropic Hormone↗
PubMed1993

Characterization of genes involved in molybdenum transport in Azotobacter vinelandii.

Expression of alternative nitrogenases in Azotobacter vinelandii is repressed by molybdenum. Two strains with Tn5 insertion mutations showed alternative nitrogenase-dependent diazotrophic growth in the presence of Mo. The mutations were in a region which contained four open reading frames (ORFs 1-4). The genetic structure and predicted products of ORFs 2, 3 and 4 are typical of the membrane-associated elements of the ATP-binding cassette (ABC) superfamily of transport systems. The products of ORF3 and ORF4 are homologous with the products of the Escherichia coli genes chlD and the partially sequenced chlJ, respectively, both of which are implicated in molybdenum transport. ORF1, which is in the relative position of bacterial permease genes commonly specifying periplasmic binding proteins, encodes a 29 kDa protein with a novel primary structure. It lacks a potential signal sequence, and its C-terminal half consists of a tandem repeat of a segment which is homologous with the M(r) 7 kDa molybdenum-pterin binding protein Mop from Clostridium pasteurianum. This suggests that a substituted pterin may be involved in the initial capture or early metabolism of molybdenum.

Amino Acid Sequence↗
PubMed1993

Effects of tibolone on serum concentrations of lipoprotein(a) in postmenopausal women.

OBJECTIVE: To evaluate the effects of tibolone (Org OD14), a synthetic steroid used for the relief of postmenopausal symptoms, on serum concentrations of lipoprotein(a) (Lp(a)), an independent risk marker for coronary heart disease. DESIGN: Subset of women participating in a non-randomized prospective trial of tibolone therapy. Twenty-seven women requesting relief of menopausal symptoms were treated with tibolone 2.5 mg/day for six months; 27 women who did not request treatment acted as controls. RESULTS: Tibolone induced a substantial fall (p < 0.001) in serum Lp(a) levels (median change -48%, range -100% to +3%). CONCLUSIONS: In terms of cardiovascular risk, the ability of tibolone to lower serum concentrations of Lp(a) may be advantageous in view of the unwanted reduction in high density lipoprotein concentrations which has previously been demonstrated in users of this steroid.

Anabolic Agents↗
PubMed1993

Gold-induced colitis: a case report and review of the literature.

A case of severe colitis requiring subtotal colectomy following administration of 35 mg Solganal b for intractable arthritis is described. Abdominal pain and watery diarrhea developed six weeks after the last dose of gold. Colonoscopy revealed mucosal edema and ulceration of the entire colon. Supportive measures failed and the patient required subtotal colectomy. Review of the literature revealed 29 cases, ranging in severity from limited ileal involvement to fulminant panenteritis. Most of the patients responded to intravenous fluids, steroids, and antibiotics, but four required surgery. The case described is notable for the delay in appearance of abdominal symptoms following the cessation of gold therapy. The mechanism of injury is unknown. Abdominal complaints in a patient who has received gold therapy, especially parenteral, merit strict attention, even if occurring several weeks after the final dose, and the diagnosis of gold colitis should be entertained.

Acute Disease↗
PubMed1992

Transcervical cannulation of the fallopian tube for the management of ectopic pregnancy: prospective multicenter study.

OBJECTIVE: To determine the efficacy of transcervical tubal cannulation and intraluminal methotrexate injection for the management of tubal ectopic pregnancy (EP). DESIGN: Prospective multicenter study of 33 patients with tubal pregnancies. SETTING: Four university-based gynecology and radiology departments in three different countries: France, England, and Germany. PATIENTS: Thirty-three patients who presented with a clinical diagnosis of EP. INTERVENTIONS: Patients underwent transcervical tubal cannulation under fluoroscopic or ultrasound control and local injection of methotrexate (up to 50 mg). MAIN OUTCOME MEASURES: We evaluate the feasibility of transcervical tubal cannulation for the management of tubal pregnancy. RESULTS: Two patients elected to withdraw from the protocol. In the remaining 31 patients there was complete resolution of the EP in 27 (87%). Surgery was performed in 4 patients. Seventeen patients, 14 of whom desired pregnancies, were available for follow-up to assess the return of reproductive potential. Seven of 7 patients who subsequently underwent hysterosalpingography had patency of the affected tube. Five patients later had an intrauterine pregnancy. One patient had an early miscarriage, two have given birth, and two singleton pregnancies are still ongoing. The remaining patients are symptom free. CONCLUSIONS: This study demonstrates that transcervical tubal catheterization in patients with tubal pregnancies is feasible and can be performed without anesthesia or analgesia in most cases. Intraluminal methotrexate per se is capable of causing regression of the EP. This approach offers a new alternative for the treatment of selected patients with tubal EP.

Adult↗
PubMed1992

Expression and gene transcript of Fc receptors for IgG, HLA class II antigens and Langerhans cells in human cervico-vaginal epithelium.

The mechanism of transmission of HIV from the male to the female genital tract or in the reverse order is not clear. CD4 glycoprotein is the receptor for HIV and Langerhans cells and the related dendritic cells could play a role in the initial transmission of HIV. Fc receptors (FcR) for IgG might be involved in antibody-mediated binding of HIV. We carried out an immunohistological study of normal human cervical and vaginal epithelia for the presence of CD4 glycoprotein, Langerhans cells and FcR to IgG. CD4+ glycoprotein was not found in the vaginal or cervical epithelium, with the exception of a few endocervical epithelial cells. A small number of CD4+ mononuclear cells were found in the endocervical epithelium of a third of the specimens but a large number of CD4+ cells was found in the submucosa of most of the cervical and vaginal specimens. Langerhans cells expressing CD4, HLA class II, Fc gamma R2 and Fc gamma R3 were detected in most vaginal, ectocervical and transformation zone epithelia and in 9/14 endocervical tissues. Fc gamma R3 was detected in about two-thirds of the columnar endocervical epithelium and the transformation zone. A smaller number of specimens expressed Fc gamma R2 in these epithelia, but Fc gamma R1 was not detected. We then demonstrated mRNA for Fc gamma R3 in the columnar endocervical epithelial cells and transformation zone by in situ hybridization, using a CD16-RNA probe. Fc gamma R3 and Fc gamma R2 gene transcripts were also found in fetal cervical tissue by applying the polymerase chain reaction to amplify portions of the Fc gamma R3 and Fc gamma R2 coding sequences in cDNA prepared from fetal RNA. HLA-DR was found in the endocervical cells, transformation zone and in Langerhans cells of all specimens. The presence of Langerhans cells, Fc gamma receptors and HLA class II antigen offers three potential mechanisms for cervico-vaginal HIV transmission: (i) direct HIV infection of Langerhans cells, (ii) binding of HIV antibody complexes to cervical epithelial Fc gamma receptors and (iii) binding of HIV infected CD4+ cells to cervical HLA class II antigen which may infect these or the adjacent CD4+ cells.

Adult↗
PubMed1992

Self-esteem, aspirations and expectations of adolescents with physical disability.

Fifteen adolescents with physical disabilities were compared with able-bodied controls by means of questionnaires to assess their self-esteem and their future aspirations and expectations. There was no significant difference for self-esteem between the two groups. This encouraging finding is inconsistent with earlier findings of low self-esteem. There was no significant correlation between the self-esteem of the physically disabled adolescents and the difference between their aspirations and expectations; however, there was a significant negative correlation for the able-bodied controls.

Adolescent↗
PubMed1991

Effects of oxygenation and pH on tumor cell response to alkylating chemotherapy.

In the present investigations we evaluated the consequence of changing the cellular microenvironment on the treatment efficacy of the alkylating chemotherapeutic agent melphalan. Human A549 adenocarcinoma and mouse KHT/iv sarcoma cells were treated with melphalan under aerobic or hypoxic conditions at pH 6.6 or 7.4. Both low oxygenation and acidic pH individually were found to increase tumor cell killing by this chemotherapeutic agent. However, the magnitude of the enhanced toxic effect was greatest when hypoxic conditions and acidic pH were combined during treatment. For example, A549 cells treated with melphalan under hypoxic conditions at pH 6.6 were approximately 3 times more sensitive to this anticancer drug than were cells exposed in air at pH 7.4. Conditions of low oxygen and pH also increased the chemosensitization potential of the nitroimidazole misonidazole (MISO) when combined with this chemotherapeutic agent. Thus, when KHT/iv cells were treated with the combination of melphalan plus MISO, the resulting enhancement ratio increased from 1.8 to 2.5, when the pH maintained during the treatment was changed from physiologic (7.4) to acidic (6.6).

Adenocarcinoma↗
PubMed1991

Injuries due to falls as a result of uneven pavements.

At least one person per day attending the A&E department at King's College Hospital has sustained injuries from uneven pavements. The injuries have a significant morbidity as well as mortality of 1%. A&E records can be a source of useful information to aid local authorities in identifying areas associated with these injuries in order to reduce their frequency and subsequent claims for compensation.

Accident Prevention↗