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Biomedical subjects

C Fisher

Publications and source records attributed to C Fisher.

At least 379 records · Page 21Linked to original sources
PubMed1990

Mutation of the p53 gene in human soft tissue sarcomas: association with abnormalities of the RB1 gene.

Soft tissue sarcomas have been examined for alterations in the p53 gene. In six sarcomas, loss or rearrangement of both alleles of this gene was detected while in a further seven sarcomas, point mutation or absence of transcription of the p53 gene was observed. Abnormalities of the p53 gene were found in several classes of soft tissue sarcoma, including leiomyosarcomas, rhabdomyosarcomas and malignant fibrous histiocytomas. Our studies also show that abnormalities of the RB1 suppressor gene and of the p53 gene frequently occur together. These results are consistent with the idea that the p53 gene is a tumour suppressor gene and indicate that coincident inactivation of more than one tumour suppressor gene may, in some cases, be required for tumour development.

Base Sequence↗
PubMed1989

Detection of point mutations in N-ras and K-ras genes of human embryonal rhabdomyosarcomas using oligonucleotide probes and the polymerase chain reaction.

Previous studies have demonstrated that genes of the ras family (H, K, and N) can be activated by point mutations at codons 12, 13, and 61. In the present study we have used oligonucleotide probes corresponding to these regions to assess the role of ras gene mutations in the genesis of human rhabdomyosarcoma. To increase the sensitivity of this method the appropriate regions of the three ras genes were first amplified using the polymerase chain reaction. The results show that 35% (5/14) embryonal rhabdomyosarcomas investigated contain mutations in the N-ras or K-ras genes. Thus ras gene mutation is implicated in the development of mesenchymal and embryonal tumors in addition to its previously documented role in epithelial and hematological neoplasia.

Adolescent↗
PubMed1989

Limb conservation for soft tissue sarcomas of the shoulder and pelvic girdles.

Fifty-five patients with soft tissue sarcomas of the shoulder and pelvic girdles were treated between 1982 and 1987 with a consistent policy of limb conservation, using a wide variety of excisional and reconstructive surgical techniques and radical radiotherapy. Actuarial 5-year overall survival was 75 per cent for patients with low or intermediate grade tumours, and 38 per cent for those with high grade tumours (log rank test, P less than 0.05). Five-year local recurrence rates were 32 per cent for low or intermediate grade tumours, and 48 per cent for high grade tumours (log rank test, not significant). Multivariate analysis of the following risk factors for overall survival was performed: age, sex, tumour site, diameter, grade, inadequate surgical margins and local recurrence. Age over 55 years and high tumour grade emerged as independent prognostic variables for survival. Forequarter or hindquarter amputations were undertaken in seven of the 55 patients for local recurrence following previous limb-conserving surgery and radiotherapy. Local failure was not always salvaged by major amputation; satisfactory proximal tumour clearance was achieved in only two of seven patients undergoing major amputation; four of the seven patients developed stump recurrence, three of whom died with uncontrolled local disease. Meticulous attention to surgical and radiotherapeutic technique is required to minimize the incidence of local recurrence while maintaining satisfactory limb function.

Actuarial Analysis↗
PubMed1989

Primary medical therapy for operable breast cancer.

Fifty-seven patients with large but potentially operable primary breast cancer were treated with primary medical therapy rather than initial mastectomy, using chemotherapy (15) or endocrine therapy (42) with the tumour remaining in situ. Of patients treated with chemotherapy, one (7%) achieved a complete remission, and eight (53%) a partial response (overall response rate 60%). Only one patient had progressive disease while on chemotherapy. Of patients who received endocrine therapy, one (2%) achieved a complete response, and 19 (45%) a partial response (overall response rate 47%). Two patients progressed on endocrine therapy. Only 10 patients have so far had a subsequent mastectomy (18%), and 17 (30%) have had radiotherapy and/or conservative surgery. The rest are still on medical therapy. With a median follow-up of 19 months (range 6-42 months) only two patients have had a local recurrence after being disease-free and none have developed uncontrollable local recurrence. Eight (14%) have developed distant metastases and four (7%) have died of metastatic disease. Primary medical therapy may offer an effective alternative to mastectomy for patients with operable breast carcinomas too large for conservative surgery and merits further study.

Adult↗
PubMed1989

Adenosquamous carcinoma of the thyroid gland.

A case of adenosquamous carcinoma of the thyroid gland is presented. This rare form of cancer behaves in an aggressive manner similar to anaplastic carcinoma and is characterized histologically by the intimate blending of the squamous and glandular elements. The prognostic significance of identifying areas of malignant squamous epithelium within papillary carcinoma as opposed to the much more common benign squamous metaplasia, is highlighted. The pathogenesis, differential diagnosis and management of the condition are discussed.

Adenocarcinoma↗
PubMed1989

Structural alterations of the RB1 gene in human soft tissue tumours.

Sixty-nine primary soft tissue tumours were examined for alterations of the RB1 gene which has previously been implicated in the genesis of retinoblastoma. In three tumours loss of both alleles of this gene (homozygous deletion) was detected. Two of these, both leiomyosarcomas, contained a chromosomal breakpoint within the RB1 gene, while in the third tumour, a radiation induced sarcoma, complete deletion was observed. Using a probe that detects a polymorphic locus within the RB1 gene we found loss of only one allele (heterozygous deletion) in 33% of soft tissue sarcomas examined, including two leiomyosarcomas, a malignant peripheral nerve sheath tumour, a rhabdomyosarcoma and a chondrosarcoma. When taken together our results suggest that alterations of the RB1 locus may play an important part in the pathogenesis of soft tissue tumours and particularly in leiomyosarcomas which accounted for four of the eight RB1 alterations observed in this study.

Alleles↗
PubMed1989

Onset of expression of peanut lectin-binding glycoproteins is correlated with stratification of keratinocytes during human epidermal development in vivo and in vitro.

During gestation the epidermis develops from a single layer of ectoderm into a layer of keratinocytes overlaid by a layer of periderm; this is followed by a progressive increase in the number of layers of keratinocytes, until finally the distinct granular and cornified layers characteristic of mature epidermis are formed. As part of our investigation into the function of the peanut lectin-binding glycoproteins of cultured human keratinocytes, we have examined their expression at different stages of human epidermal development. We found that the onset of expression of the glycoproteins coincided with the transition from a two- to a three-layered epidermis, both in vivo and in organ culture. In adult epidermis, the patterns of binding of peanut lectin and Limax flavus lectin are complementary, with peanut binding more strongly to suprabasal keratinocytes and Limax flavus lectin binding more strongly to cells in the basal layer. We found that the complementary pattern of binding of the two lectins was established at, or shortly after, the onset of stratification and retained throughout development. In contrast, expression by keratinocytes of involucrin, a protein precursor of the cornified envelope, occurred after stratification had begun. Finally, we identified the peanut lectin-binding glycoproteins of adult epidermis by immunoblotting with an antiserum raised against the glycoproteins of cultured neonatal keratinocytes. In conclusion, expression of the peanut lectin-binding glycoproteins is an early event in epidermal development, and this would be consistent with a role for the glycoproteins in stratification.

Embryonic and Fetal Development↗
PubMed1989

Characterization of the translocation between chromosomes X and 18 in human synovial sarcomas.

Recent studies have identified a specific chromosomal translocation, t(X;18)(p11.2;q11.2), in a high proportion of human synovial sarcomas. As a first step towards characterizing the X;18 translocation we have established a synovial sarcoma cell line. Fusion of this cell line to mouse RAG cells gave rise to somatic cell hybrids that contain the derivative (X) marker chromosome in the absence of other genetic material from chromosomes 18 and X. Southern analysis of DNA from these somatic cell hybrids demonstrated that the human X chromosome markers DXS94, DXS14, DXZ1 and DXS62 were retained. In contrast DXS7, GAPDP1, ARAF1, DXS146 were not consistently present in the hybrids indicating that these markers were on the region of the X chromosome replaced by part of the long arm of chromosome 18 during the generation of the X;18 translocation. The predicted position of the translocation relative to X chromosome markers is DXS7-DXS146-X; 18-DXS14-DXZ1-DXS94.

Chromosome Banding↗
PubMed1988

The impact of hydronephrosis on renal function in patients treated with cisplatin-based chemotherapy for metastatic nonseminomatous germ cell tumors.

We analysed renal function before and after chemotherapy in 130 patients with large (greater than 5 cm in diameter) abdominal masses from malignant non-seminomatous germ cell tumors (NSGCT). The mean glomerular filtration rate assessed by 51Chromium (51Cr) ethylenediamine tetraacetic acid (EDTA) clearance was lower in 46 patients with radiologic evidence of hydronephrosis than in 84 patients with abdominal masses but no hydronephrosis (102 ml/min versus 139 ml/min; P less than 0.01). Patients with hydronephrosis who were treated with cisplatin-based chemotherapy demonstrated a slight early improvement in renal function followed by a fall, in contrast to those treated with carboplatin-based chemotherapy in whom renal function improved. Patients with hydronephrosis who showed no improvement in glomerular filtration rate after the first course of chemotherapy were at an increased risk of renal atrophy and chronic renal damage developing. Long-term renal toxicity may be avoided in these patients either by the use of carboplatin or by the use of drainage procedures such as ureteric stenting or nephrostomy.

Adolescent↗
PubMed1988

Colic, "overfeeding", and symptoms of lactose malabsorption in the breast-fed baby: a possible artifact of feed management?

Curtailing the time for which a baby feeds at the first breast, in order to encourage intake from the second breast, may maximise milk production by the mother. With escalation of this situation a point may be reached at which the infant, because of the constraint of his stomach capacity, is unable to consume sufficient calories at a feed, since foremilk is lower in calories than hindmilk. The result will be symptoms of hunger (crying, fretfulness) and maybe even failure to thrive. The low fat content of the diet may cause rapid gastric emptying. This in turn may lead to lactose reaching the small bowel in concentrations that may tax the infant's lactase potential, with resulting diarrhoea. A simple change in breastfeeding patterns may alleviate some instances of undernutrition or diarrhoea.

Breast Feeding↗
PubMed1988

Purification, properties and cation activation of galactosyltransferase from lactating-rat mammary Golgi membranes.

Galactosyltransferase was purified from Golgi membranes of lactating-rat mammary gland and studied with respect to its physical and enzymic (lactose synthetase) properties. The enzyme occurred in both monomeric (43-46 kDa) and apparently dimeric (90 kDa) forms. It was very unstable except in the presence of phospholipid, detergent, or cations binding to site 2. The amino acid composition and the N-terminal sequence closely resembled that of the human and bovine milk enzymes, particularly in respect to a Pro-Pro-Pro-Pro sequence. Kinetic studies demonstrated a high-affinity Mn2+-binding site (1) essential for activity, and a low-affinity Mn2+-binding site (2) that could also bind spermidine or clupeine. Mn2+ binding at site 2 raised Vmax fivefold. Spermidine binding at site 2 enhanced Mn2+ binding at site 1, and influenced binding of glucose. At physiological glucose concentration, clupeine or spermidine activated nearly as well as 15 mM MnCl2 and are regarded as models of a natural cation activator that remains to be isolated. Evidence is given for an essential histidine residue in the galactosyltransferase. It is proposed that site 1 Mn2+ participates directly in the reaction mechanism, whereas site 2 is a regulator site allosterically activated by a basic protein.

Amino Acid Sequence↗
PubMed1988

A phase I-II study of ifosfamide in combination with adriamycin in the treatment of adult soft tissue sarcoma.

Fifty-four patients with advanced soft tissue sarcoma were treated with a combination of ifosfamide (5 g/m2) and adriamycin (40-60 mg/m2) at 3 weekly intervals. Of the 50 evaluable patients a response was seen in 11 (22%) patients (3 complete and 8 partial responses), stabilization of disease occurred in 17 patients and the remaining 22 patients progressed whilst on treatment. Of the 22 patients receiving adriamycin 60 mg/m2 12 (55%) required a dose reduction due to toxicity compared to 11 (39%) of the 28 patients who received 40 mg/m2. For the patients who had a response the median relapse-free interval was 7 months (range 2-17+) and the overall median survival was 12 months (range 5-29+). The combination does not appear to show an advantage over either drug used as a single agent.

Adolescent↗
PubMed1988

Duplex imaging of in situ saphenous vein bypass grafts and late failure reduction.

Duplex ultrasonic scanning was applied prospectively to 20 consecutive cases of in situ saphenous vein infrainguinal bypass 1, 3, 6, and 12 months postoperatively. All 20 (100 percent) and 17 of 19 (90 percent) of the proximal and distal anastomoses, respectively, could be imaged satisfactorily. Graft velocity ranged from 30 to 100 cm/s. Of three grafts with low velocity, one had impending graft failure and two had inherently low velocity but remained patent. Five defects in three grafts were detected. In three cases, intervention prevented graft failure. The primary patency rate was 80 percent, but was improved to 95 percent as a result of graft surveillance and simple revisions. Duplex scanning is a superior method for postoperative in situ saphenous vein bypass surveillance. We recommend that patients be studied 1 month postoperatively and every 3 to 6 months thereafter.

Adult↗
PubMed1988

Epithelioid sarcoma: the spectrum of ultrastructural differentiation in seven immunohistochemically defined cases.

Seven epithelioid sarcomas were examined by light and electron microscopy and by immunohistochemical methods for the presence of vimentin and the epithelial markers keratin and epithelial membrane antigen. All the tumors displayed vimentin and both epithelial markers. Electron microscopy showed a spectrum of cellular differentiation from primitive fibrohistiocytic cells to epithelial-type cells with junctions, microvilli, and tonofilaments. Spindle cells showed myofibroblastic and fibroblastic differentiation. Epithelioid sarcoma appears to be a tumor of primitive cells with the potential for mesenchymal and epithelial differentiation, like some embryonic tumors.

Adolescent↗