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Biomedical subjects

C Fisher

Publications and source records attributed to C Fisher.

At least 271 records · Page 15Linked to original sources
PubMed1994

Changes in oncogene mRNA expression during human keratinocyte differentiation.

The nuclear proto-oncogenes are involved in transcriptional regulation and control many cell processes. The role of changes in proto-oncogene expression in controlling the balance between proliferation and differentiation was studied in cultured keratinocytes. Normal human keratinocytes were grown in the serum-free medium MCDB153 with an extracellular calcium concentration of 70 microM. After treatment with different differentiation conditions, cellular RNA was size-fractionated on agarose gels and transferred to nylon membranes which were subsequently hybridized with c-myc, c-jun, and H-ras 32P-labelled probes. Relative RNA loading was assessed using probes for beta-actin and ribosomal 18s RNA. Inducing differentiation by increasing the calcium concentration of the medium from 70 microM to 1.5 mM resulted in a marked decrease in c-myc RNA levels to 26% of control levels within 8 h. After 48 h in 1.5 mM calcium, c-myc levels had recovered to approximately 50% of control levels. There was a gradual reduction in c-jun levels to 56% of control levels by 4 days. Treatment with 10 nM TPA, which also induces keratinocyte differentiation, reduced c-myc RNA levels to 70% of control levels during the first 4 h, but thereafter c-myc levels remained approximately constant for a further 20 h. TGF beta (2 ng/ml), which inhibits keratinocyte growth without inducing differentiation, did not alter c-myc RNA levels over a 4-day period. There were no changes in c-myc levels following the addition of retinoic acid and none of the conditions altered H-ras levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1994

The use of a shared donor oocyte program to evaluate the effect of uterine senescence.

OBJECTIVE: To determine if there is reduced uterine receptivity after age 40 by the comparison of pregnancy rates (PRs) of donor oocyte recipients > or = 40 years to those under age 40. SETTING: In vitro fertilization-ET facility of a university-based practice, Cooper Institute for In Vitro Fertilization. PATIENTS: All patients registering for the shared donor oocyte program from November 1990 to September 1992. Most recipients were in ovarian failure. INTERVENTIONS: Donors were treated with luteal phase leuprolide acetate (LA) and gonadotropins; recipients were treated with oral E2 in graduated doses and 50 mg IM daily P. Endometrial thickness was considered in the decision to continue with transfer or to freeze all embryos. MAIN OUTCOME MEASURES: Pregnancy rates per transfer in recipients and live birth rates according to age > or = 40 or < 40. RESULTS: The clinical PR per transfer was 29.2% for the younger women and 25.4% for the older recipients. The live birth rate was 29.2% for the younger women and 22.4% for the older recipients. CONCLUSIONS: These data support the conclusion that, if there is a decline in uterine receptivity for embryo implantation with advancing age, it is at least remediable with hormonal adjustments.

Adult↗
PubMed1994

Primary chemotherapy for stage II nonseminomatous germ cell tumors of the testis.

Between 1979 and 1989, 122 patients with clinical stage II testicular nonseminoma were treated with primary platinum-based combination chemotherapy following orchiectomy. Of the patients 58 had Royal Marsden Hospital stage IIA (nodes less than 2 cm. in diameter) and the other 64 had stage IIB (nodes 2 to 5 cm. diameter) disease. With a median followup after chemotherapy of 5.5 years, 118 patients (97%) were disease-free. Two patients died of progressive germ cell tumors, 1 of bleomycin toxicity and 1 of coincidental disease. The 5-year actuarial survival probability was 95% (95% confidence intervals 91 to 99%) and the 5-year failure-free survival probability was 92% (95% confidence intervals 88 to 97%). Tumor substage was not predictive of relapse but did indicate the probability of lymphadenectomy for a post-chemotherapy residual mass since this was performed in 17% of the patients with stage IIA disease and 39% with stage IIB disease (p < 0.05). Resected specimens contained mature teratoma (29), necrosis alone (5) or embryonal carcinoma (1). We conclude that for these clinical stages primary chemotherapy was as effective as primary lymph node dissection and a major operation was avoided in 68% of the cases.

Actuarial Analysis↗
PubMed1994

Six-month results of the multicenter phase I study of excimer laser myopic keratomileusis.

We report six-month results of the Summit Technology Myopic Keratomileusis Phase I multicenter study. Fifty-seven eyes of 57 patients had keratomileusis to correct high myopia. A microkeratome was used for the primary keratectomy and the excimer laser was used to ablate the stroma of the resected lenticle (cap) or the stromal bed (in situ). At six months, 31 of the 47 eyes available for follow-up (65.9%) had uncorrected visual acuity of 20/40 or better; 16 (34.0%) had uncorrected acuity of 20/25 or better. Thirty-seven eyes (78.7%) maintained the same (+/- one Snellen line) best corrected visual acuity as before surgery; seven (14.9%) lost two lines and three (6.4%) lost more than two lines. In addition to the six-month multicenter study results, we report two year results in a subset of 28 eyes (22 from the multicenter study and six fellow eyes). At six months, 17 of the 24 eyes available for follow-up (70.9%) had uncorrected visual acuity of 20/40 or better and nine (37.5%) had uncorrected acuity of 20/25 or better, including eyes that had worse than 20/80 best corrected visual acuity preoperatively. At 24 months, five of the seven eyes available for follow-up (71.4%) had uncorrected acuity of 20/25 or better. Only one patient lost two lines of best corrected vision at six months and no patient lost more than two lines; at 24 months, all patients maintained (+/- one line) best corrected vision.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Two malignant salivary gland tumours of different type in one patient.

The synchronous or metachronous occurrence of two tumours of the salivary glands in one patient is rare. These are mainly benign and of the same histological type. Here we report a 56-year-old man who developed a mucoepidermoid tumour of the left parotid gland four years after diagnosis of adenoid cystic carcinoma of the right submandibular gland. This combination of neoplasms has not to our knowledge been reported before.

Carcinoma, Adenoid Cystic↗
PubMed1994

Abnormalities of the p53 MDM2 and DCC genes in human leiomyosarcomas.

In this study we have screened a series of 29 primary leiomyosarcomas for abnormalities of both the p53 gene and the MDM2 gene, which encodes a p53-associated protein. SSCP (single-strand conformation polymorphism) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA were used to establish that 6/29 tumours possessed point mutations of the p53 gene. Using a monoclonal antibody that recognises the p53 protein in immunohistochemical staining experiments, we observed overexpression of the p53 protein in five of the six tumours containing point mutations in the p53 gene. Southern analysis of tumour DNA revealed that 2/29 tumours demonstrated amplification of the MDM2 gene. When considered together, these results indicate that alterations in both the p53 gene and MDM2 gene are important in the development of a significant minority of leiomyosarcomas. In addition, we have demonstrated a significant association between the presence of abnormalities of the p53 gene or MDM2 genes in leiomyosarcomas and a more advanced clinicopathological stage (P = 0.03). We have also examined the role of the DCC tumour-suppressor gene in the development of human soft-tissue tumours in a variety of histological types. Except for evidence of a rearrangement in a single leiomyosarcoma cell line, SK-UT-1, we have found no direct evidence to support a role for mutation of the gene in the development of human soft-tissue tumours.

Adult↗
PubMed1994

Induction of transforming growth factor beta in hormonally treated human prostate cancer.

Transforming growth factor beta-1 (TGF-beta 1) has been proposed as a mediator of tumour growth in a number of tumours and cell lines including prostate, and in a recent study was shown to be up-regulated in the stroma of breast cancer tissue following treatment with the anti-oestrogen tamoxifen. Immunolocalisation of the intracellular form of TGF-beta 1 confirmed that the source of the stromal TGF-beta 1 was the peritumoral fibroblasts. We present here the results of a study in which five patients with hormonally unresponsive prostatic carcinoma and seven patients responding to a luteinising hormone-releasing hormone analogue had prostate biopsies taken before and during treatment. These were stained for TGF-beta expression prior to treatment and at either relapse or 3 months later respectively. Six of seven clinically responding tumours and three of five relapsed tumours showed up-regulation of extracellular TGF-beta 1, again primarily in the stroma, with no apparent up-regulation of intracellular TGF-beta 1, TGF-beta 2 or TGF-beta 3. These data illustrate that the epithelial growth inhibitor TGF-beta 1 can be induced by hormonal manipulation in prostate cancer in vivo, and may continue to be up-regulated even after relapse. This suggests that relapse of hormonally treated prostate cancer may be associated with a failure of the epithelium to respond to stromal TGF-beta 1.

Androgens↗
PubMed1994

Generation of interleukin-2-secreting melanoma cell populations from resected metastatic tumors.

This study aimed to determine the feasibility of producing patient-specific, interleukin-2 (IL-2)-secreting tumor cell vaccines for the treatment of metastatic melanoma. Primary tumor cell cultures were established from 26/33 resected metastatic melanoma samples. Recombinant retroviral gene transfer and expression in these cultures was optimized using an amphotropic, defective retrovirus carrying the LacZ gene. All cell cultures were infectable; those that proliferated more rapidly were infected at a higher frequency. Addition of fibroblast growth factor to the culture medium increased the rate of cell proliferation and the efficiency of infection. A single infection with an identical retrovirus carrying a human IL-2 cDNA resulted in the generation of unselected cell populations secreting up to 300 units IL-2/10(6) cells.48 hr. Multiple infections increased the level of IL-2 secretion to 5,000 units/10(6) cells.48 hr. The recombinant viral genome could be detected at approximately single copy in the multiply infected cells; no helper virus was detected. IL-2 secretion from infected cultures was maintained following cryopreservation and x-irradiation. These data demonstrate that heterogeneous tumor cell populations secreting IL-2 can be generated from individual patients to be used as autologous, irradiated cell vaccines.

DNA, Neoplasm↗
PubMed1994

Nitrogen balance, plasma free amino acid concentrations and urinary orotic acid excretion during long-term fasting in cats.

The purpose of this study was to ascertain the changes in nitrogen balance, plasma free amino acid concentrations, urinary orotic acid excretion and body weight during long-term fasting in adult obese cats. Results from eight cats that fasted rather than eat an unpalatable diet are reported. After 5 to 6 wk of weight loss, six of the eight cats developed signs of hepatic lipidosis, and the livers of all cats were severely infiltrated with lipids. Cats lost (mean +/- SE) 33.2 +/- 1.4% of their pre-fasting body weight. Mean nitrogen balance (+/- SE) was -547 +/- 54 mg.d-1.kg-2/3 for the first week, and then the net nitrogen losses decreased to a plateau (-303 +/- 52 mg.d-1.kg-2/3) after 4 wk. Fasting was associated with a decrease in plasma concentration of essential amino acids. When plasma amino acid concentrations were considered individually, concentrations of alanine, methionine, taurine, citrulline, arginine and tryptophan decreased the most (> or = 50%), whereas concentrations of glutamine, glutamate and ornithine significantly increased. Orotic acid was not detected in the urine during the fast. After 1 wk of fasting, obese cats had reduced nitrogen excretion, but not to the same extent as has been shown in obese humans or obese rats. It is suggested that the availability of several amino acids may become limiting for liver protein synthesis during fasting and that these deficiencies may contribute to the development of hepatic lipidosis. Orotic acid was not linked to hepatic lipidosis caused by fasting in cats.

Amino Acids, Essential↗
PubMed1994

The endodermal sinus tumour and clear cell ovarian cancer.

There are similarities between clear cell epithelial ovarian carcinoma and endodermal sinus tumours. Apart from the morphological and clinical characteristics there are immunohistochemical markers of value in differentiating these 2 tumours and the detection of a raised serum AFP is characteristic of endodermal sinus tumours. These 3 cases we describe show the fallibility of the classical differentiating criteria between these two tumours.

Adenocarcinoma, Clear Cell↗
PubMed1994

Atypical carcinoid tumour of the thymus: a study of eight cases.

Atypical carcinoids of the thymus are rare neoplasms of uncertain prognosis. We have studied eight cases (six male, two female; age range 48-60 years, mean 55 years), none with evidence of a paraneoplastic neuroendocrine syndrome. Tumour size was large and ranged from 7.5 to 10 cm. Microscopically, all had a nesting/insular or trabecular pattern, eosinophilic cytoplasm, round nuclei with fine chromatin and small nucleoli. No small cell features were evident. Mitotic activity ranged from 2 to 21 per 1.52 mm2. Focal necrosis was seen in all cases. All were positive for cytokeratin (AE1/AE3, CAM 5.2) and the neuroendocrine markers NSE, synaptophysin and chromogranin; five cases were positive for calcitonin. On electronmicroscopy all contained dense core granules, often numerous. Three cases were stage I and five stage III (infiltrating lung or chest wall). Follow-up information was available in four cases (one stage I and three stage III): the stage I tumour had local recurrence and metastasis to the lung within a year whilst the three patients with stage III tumours died of liver, bone and brain metastases within 3 years.

Carcinoid Tumor↗
PubMed1994

Vacuolation in prostate cancer cells following luteinizing hormone releasing hormone analogue treatment.

OBJECTIVE: To assess whether the 'oestrogen effect' of vacuolation in treated prostatic cancer cells is seen after luteinizing hormone releasing hormone (LHRH) analogue therapy. PATIENTS AND METHODS: Eight patients with locally advanced prostate cancer were treated with the LHRH analogue, leuprorelin acetate. Biopsies taken pretreatment and after 3 months were assessed for the presence or absence of microscopic vacuolation. RESULTS: Seven out of eight patients had evidence of vacuolation induced or accentuated by treatment. CONCLUSIONS: Recent research suggests that both stilboestrol and LHRH analogues have a direct cytotoxic effect on prostate cell lines in vitro, which appears to be supported by these findings. Vacuolation seems to be a normal consequence of treatment with LHRH analogues.

Biopsy↗
PubMed1994

Prognosis of testicular teratoma differentiated.

OBJECTIVE: To determine whether the clinical course of patients with testicular teratoma differentiated (TD) and those with testicular teratoma undifferentiated justify a different follow-up protocol. PATIENTS AND METHODS: Between 1979 and 1989, 16 adult patients with testicular TD were treated at the Royal Marsden Hospital. These represented 2.7% of the 592 testicular teratoma patients seen during this period. With the exception of a propensity to involve the right testis (76%), there were no differences in clinical presentation between TD and non-TD histological subtypes. RESULTS: The mean follow-up was 55 months (range 7-137). Seven of the 16 patients had Stage I disease and were entered into surveillance programmes; one relapsed at 7 months. Ten men were treated with cisplatin or carboplatin-based chemotherapy for metastases, of whom three had had prior chemotherapy at other hospitals and were referred after relapse. In the seven previously-untreated chemotherapy group two patients failed. In the concurrent era, 375 patients with other subtypes of metastatic testicular non-seminoma were treated with chemotherapy and 47 (12.5%) failed (Progress Free Survival chi square (chi 2) = 2.73, P = 0.01). Although no difference in progression-free survival was demonstrated between TD and non-TD patients, the former had a worse overall survival probability (chi 2 = 9.02, P = 0.003); this may be an artefact due to the small number of events. CONCLUSION: Despite the apparently more benign histology, it is recommended that the management of adult TD should not deviate from the general principles established for other histological subtypes of testicular teratoma.

Adult↗
PubMed1994

Serum lipids and apolipoproteins and their relationship with macrovascular disease in type 1 diabetes.

In order to examine the relationship between serum lipids and apolipoproteins and macrovascular disease in patients with Type 1 diabetes mellitus, 50 patients with Type 1 diabetes mellitus attending the diabetic clinics at St Mary's and St Charles' Hospitals, London were recruited into a cross-sectional study. B-mode ultrasound was used to measure intima-media thickness and define an arterial ultrasound score for each patient as a non-invasive indicator of atherosclerotic change. Intima-medial (i-m) thickness was significantly higher in those subjects with clinical evidence of macrovascular disease compared to those without macrovascular disease (0.865 +/- 0.191 vs 0.695 +/- 0.162 mm, p = 0.0038). In the study group there were significant correlations between i-m thickness and age (r = 0.65, p < 0.01), total serum cholesterol (r = 0.32, p < 0.01), and serum fibrinogen (r = 0.43, p < 0.01) but no other lipid or apolipoprotein variable. When i-m thickness was corrected for age there were significant correlations with total cholesterol (r = 0.43, p < 0.01) and LDL-cholesterol (r = 0.42, p < 0.01). Whereas total and LDL-cholesterol and serum fibrinogen concentrations were related to the extent of atherosclerotic disease by ultrasound techniques, there was no relationship with high density lipoprotein (HDL) or subfraction cholesterol concentrations. HDL-cholesterol may not be a useful marker for cardiovascular disease in Type 1 diabetes.

Adult↗