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Biomedical subjects

A Busuttil

Publications and source records attributed to A Busuttil.

At least 145 records · Page 8Linked to original sources

HRAS1-selected, chromosome-mediated transformants vary in phenotype in vitro and tumorigenic potential in vivo.

Transfection of mouse C127 cells with mitotic chromosomes isolated from a human EJ bladder carcinoma cell line gave rise, at high frequency, to foci of transformed cells. Independent, HRAS1-selected chromosome-mediated transformants displayed distinctive cellular morphologies in monolayer culture and colony-forming abilities in low-melting-point agarose. Subcutaneous inoculation of neonatally thymectomized, Ara-C-protected, total-body-irradiated CBA mice was used to compare the tumorigenic potential of each transformant. Significant quantitative and qualitative differences in tumorigenicity were found between transformants which correlated with differences in malignant phenotype observed in vitro. The sensitivity of the tumorigenicity assay is such that rare transformation events can be selected directly in vivo.

Animals↗

Androgen receptors in cancer of the prostate. Correlation with the stage and grade of the tumor.

The authors have measured the androgen receptor concentrations in the cytosol and nucleus of 13 carcinoma of the prostate (CaP) patients and compared these values to those in an age-matched group of 23 patients with benign prostatic hyperplasia (BPH). Histologic classification of the tumors was carried out and the receptor content was correlated to the grade and stage of the disease. The mean +/- SEM receptor values for BPH (cytosol: 115 +/- 18 fmol/g tissue; nucleus: 140 +/- 34 fmol/g tissue) were not significantly different from those measured in CaP (cytosol: 105 +/- 23 fmol/g tissue; nucleus: 83 +/- 23 fmol/g tissue). There was a positive correlation between nuclear and cytosolic receptors in both BPH and CaP. Our data revealed, however, the absence of any correlation between histologic grade in CaP and receptor content. If, however, the tumors were classified according to the stage of the cancer using the TNM system, "early disease" tumors maintained significantly lower Gleason score (4.4 +/- 0.61) and receptor levels (cytosol: 63.8 +/- 31.2 fmol/g tissue; nucleus: 46.2 +/- 26.5 fmol/g tissue) than those measured in the "late disease" (Gleason score: 7.0 +/- 0.56; cytosol receptor: 146.2 +/- 20.5; nuclear receptor: 117.2 +/- 31.6) (P less than 0.05); therefore the staging of the disease bears a great impact on the capacity of the tumor to specifically bind androgens.

Aged↗

The gross pathology and histological features of tumours produced by inoculation of human cell lines into immune-deprived mice.

Tumours were raised in both congenitally athymic ('nude') Swiss mice and in neonatally thymectomized, Ara-C-protected, whole-body irradiated CBA mice by subcutaneous inoculation of cells from a variety of cultured human lines. In both types of animal, tumours tended to grow massively at the site of inoculation, with some infiltration of adjacent tissues but only rarely with evidence of metastatic spread. Tumours derived from Burkitt's lymphoma (BL) lines or from EB virus-transformed lymphoblastoid cell lines (LCL) were all classified as high grade malignant lymphomas with a limited range of appearances on conventional histological examination. In the material studied there were no consistent features distinguishing BL-derived from LCL-derived tumours. Cell lines originating from other haematopoietic malignancies tended to produce tumours interpreted as immunoblastic lymphomas though there were distinctive characteristics in some cases, such as highly convoluted or pleomorphic nuclei in the cells of some tumours derived from T-cell leukaemia lines and plasmacytoid differentiation in tumours originating from myeloma lines. Malignant cell lines of epithelial origin gave rise to tumours with the histological appearances of anaplastic carcinomas readily distinguishable from the high grade lymphomas produced by haematopoietic cells.

Animals↗

Prevalence and "incidence" of celiac disease in Edinburgh and the Lothian region of Scotland.

After review of hospital records and jejunal biopsy sections, 703 cases of celiac disease, including 74 cases with dermatitis herpetiformis, were identified in Edinburgh and the Lothian region up to December 31, 1979. Of these, 469 were resident in Lothian, resulting in an overall prevalence of 50/100,000 in men and 74/100,000 in women. The prevalence in men showed no significant variation with age, whereas in women age-specific prevalence varied markedly, with a peak of 126/100,000 at ages 35-44 yr and a low of 28/100,000 at ages 45-54 yr. This variation could not readily be explained, although reduced case ascertainment among women born between 1925 and 1934 could be the basis of a modest cohort effect. There was no evidence that migration or increased mortality at particular ages might be alternative explanations. In children the incidence of celiac disease, as measured by cumulative prevalence with age, increased more than twofold between 1960 and 1975, but since 1976 it has fallen sharply. The fall in incidence in children and the unexplained variations in prevalence in women provide epidemiologic evidence for the role of environmental factors other than gluten ingestion in the etiology of celiac disease.

Adolescent↗

A pathological classification of nasal fractures.

The management of nasal fractures has been found by several authors to be inadequate. The reason for this is obscure but may be poor understanding of the pathology of nasal fractures. There is no adequate comprehensive classification of nasal fractures. Various weights were dropped on cadavers' noses and the resultant fractured nasal pyramid was dissected out. The fracture lines are described and particular reference is directed to the involvement of the septum in grossly deviated noses. Confirmation of septal involvement is obtained using a CAT scanner. It has been found that correction of this septal involvement at the time of manipulation significantly improves the end-results (Murray and Maran, 1984).

Humans↗

Identifying leucocytes and leucocyte subpopulations in semen using monoclonal antibody probes.

An indirect immunoperoxidase technique employing specific monoclonal antibodies has been used to identify leucocyte subpopulations in cytocentrifuge smears of washed human ejaculate. Cells reacting with the pan antihuman leucocyte monoclonal antibody (HLe-1) were demonstrated in 63/67 specimens from subfertile patients with a mean count of 14.5 +/- 17.1 leucocytes per HPF (X 320). Cells with similar reactivity were observed in all specimens examined from 10 fertile men with a mean count of 41.6 +/- 26.3 leucocytes per HPF (X 320). Leu-T4+ cells (T-lymphocytes) were demonstrated in only 13/63 of the subfertile group with a mean count of 4.46 +/- 3.3 T-lymphocytes per HPF (X 320). Studies with the anti-leu 2a antibody revealed that these leu-4+ cells were mainly of the suppressor/cytotoxic phenotype. In contrast, no leu-4+ cells were detected in the control group. No leu-12+ cells (B-lymphocytes) were detected in any of the 80 specimens examined.

Antibodies, Monoclonal↗

Transmission electron microscopy of jejunum, ileum, and caecum tissues from rats fed with gums arabic, karaya and tragacanth.

Transmission electron microscopy has been used to study the ultrastructure of rat jejunum, ileum and caecum after dietary supplementation with 10% (w/w) gum arabic, 7% (w/w) gum karaya, 4% (w/w) gum tragacanth for 45 days. Scrutiny of 65 micrographs, undertaken independently by 2 specialists, revealed no abnormalities in any of the organelles in any of the micrographs. Twelve representative micrographs are reproduced here.

Animals↗

The growth and histological characteristics of a series of human bladder cancer xenografts.

Xenografts from human transitional cell carcinoma of the bladder (TCC) have been successfully established in CBA mice which had previously been immune-deprived by thymectomy and whole body irradiation with cytosine arabinoside pre-treatment. Xenografts were established from 3/17 patients with histological grade 2 tumours, 3/19 patients with histological grade 3 tumours, and one from a patient with a mixed transitional cell and squamous cell carcinoma. No xenografts were established from patients with histological grade 1 tumours. All the xenografts maintained the histological characteristics of their parent tumours in early passage, but some developed more prominent squamous features in later generations. Many of the xenografts were cystic.

Animals↗

Immunohistochemical identification of lymphocyte subsets and macrophages in normal human urothelium using monoclonal antibodies.

Monoclonal antibodies were used to examine the pattern of distribution of lymphocyte subpopulations and macrophages in normal human urothelium. T lymphocytes (T11-positive cells) were demonstrated within the epithelium and within the lamina propria of both the ureter and the urinary bladder. Suppressor/cytotoxic T cells (T8-positive cells) predominated, with the average ratio of suppressor/cytotoxic T cells to the helper/inducer T cells being approximately 8.9 in the epithelium and 1.5 in the lamina propria. Leu M3+ cells (monocytes/macrophages) were detected in both epithelium and lamina propria. The character and distribution of these immunocompetent cells within the urothelium suggest a protective function, especially against infection and in tumour surveillance.

Antibodies, Monoclonal↗

Function of the anal sphincters after chronic radiation injury.

Anorectal manometry was done in 10 men with chronic radiation proctitis and symptoms of urgency, frequency, and occasional incontinence of faeces. They were compared with 10 asymptomatic age and sex-matched controls. The maximum resting anal canal pressure and the physiological sphincter length were significantly lower (p less than 0.01) in the irradiated group. The rectosphincteric reflex was absent in one patient and showed abnormalities of recovery in four others, who had received radiotherapy. The squeeze pressure of the external sphincter was not significantly different. These results indicate that dysfunction of the internal anal sphincter may contribute to patients' anorectal symptoms after pelvic radiotherapy. Histological evidence suggests that damage to the myenteric plexus is mainly responsible. The manometric function of the external sphincter remains relatively unaffected.

Aged↗

Fatal intraperitoneal haemorrhage of hepatic origin.

Eight cases of fatal haemoperitoneum due to liver bleeding are reported. Two followed trauma (liver biopsy and cholecystectomy). The remaining six were spontaneous, 5 being due to malignant liver disease. The sixth case due to polycystic liver disease appears to be unique. The aetiology and importance of spontaneous hepatic bleeding is discussed.

Adult↗

Resectable colonic carcinoma--a five year experience.

Clinical characteristics, mode of presentation and pathological features of resectable carcinoma of the colon have been studied in 224 cases presenting between January 1971 and December 1975. Minimum length of follow-up is five years and is complete. Forty-three per cent of patients survived five years or more, only 23 per cent of tumours being early in histological terms. The conventional high risk groups contributed little to the total and their active surveillance will not significantly improve the overall statistics.

Adult↗

The impact of chemotherapy on small cell carcinoma of the bronchus.

Between 1971 and 1978, 140 cases of small cell anaplastic carcinoma of the bronchus were registered by a group of chest physicians in north Edinburgh. Sixty-five of these patients received specific treatment either with radiotherapy or cyclophosphamide and 75 patients were given treatment for symptoms only. Between 1979 and 1981 83 patients referred to the same physicians and pathologists were treated with combination chemotherapy (methotrexate, cyclophosphamide and CCNU) for 12 weeks. Overall median survival in the 1971 to 1978 group was two months with the actively-treated patients surviving for five months vs. less than one month for treatment of symptoms only. For the 83 patients treated with combination chemotherapy, median survival was nine months with 33 per cent alive at one year and 13 per cent at two years. Positive factors associated with prolonged survival included performance status at presentation and response to chemotherapy. This study demonstrates that the prognosis for the majority of patients with small cell carcinoma of the bronchus has improved significantly with the introduction of combination chemotherapy.

Adult↗

Correlation of clinical and manometric abnormalities of rectal function following chronic radiation injury.

Continuous fluid-inflation proctometrograms were performed in men with the symptoms of chronic radiation proctitis and in age and sex-matched control subjects (n = 10). Rectal volumes and compliance were measured. There was a significant reduction in the rectal volumes at sensory threshold, constant sensation and maximal tolerance and in rectal compliance (P less than 0.01). Comparable pressure measurements did not demonstrate significant differences. The maximum tolerable volume, symptomatic and sigmoidoscopic scoring correlated to rectal compliance (r = 0.77, -0.8, -0.73; P less than 0.01, less than 0.01, less than 0.02, respectively). Reduction in volume and compliance is often not obvious radiologically. Histological evidence suggests that smooth muscle hypertrophy and myenteric plexus damage are contributory.

Aged↗

5 Alpha-reductase activity in human prostate cancer is related to the histological differentiation of the tumour.

We have measured the activities of two androgen metabolizing enzymes in tissue obtained from thirty-nine patients with carcinoma of the prostate (CaP). The enzyme activities were correlated to the histological differentiation of the tumours based on the Gleason Score and also compared to the activities measured in fourteen age matched patients with nodular prostatic hyperplasia (BPH). Although the mean values for the 5 alpha-reductase in CaP (9.29 +/- 1.47 pmol/mg protein/30 min) were found to be significantly lower than the corresponding values in BPH (16.26 +/- 3.04 pmol/mg protein/30 min) (P less than 0.05), there were nonetheless significant differences within the cancer group and these were totally dependent on the degree of differentiation of the tumour. A progressively suppressed enzyme activity was measured as the carcinomatous tissue became more anaplastic. No correlation was, however, observed between tumour bulk which was also estimated histologically and 5 alpha-reductase, indicating that the activity of this enzyme is purely a function of the histological grade of the cancer and as such 5 alpha-reductase could be used as a biochemical marker for tumour differentiation. We also measured the 3 alpha (beta)-hydroxysteroid dehydrogenase activities in cancer of the prostate but our findings indicated no significant differences between the various stages of the cancer. Furthermore we were unable to correlate the activities of this enzyme with that of the 5 alpha-reductase. Nonetheless two interesting patterns relating to the 3 alpha (beta)-hydroxysteroid dehydrogenase emerged.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗

Lymphocyte sub-populations in the male genital tract.

A series of monoclonal antibodies that react with human lymphocyte subsets was used in an indirect immunoperoxidase technique to study representative blocks from normal human testis, epididymis, vas deferens, prostate and seminal vesicles. Biopsies of testis, epididymis and vas obtained during surgical procedures directed at the investigation and treatment of infertile males were also studied. In all normal tissues, apart from the peripheral testis where no lymphocytes were identified, T lymphocytes were the predominant cell type (Leu 4+). These lymphocytes were largely of the suppressor/cytotoxic phenotype (Leu 2a+) and were more abundant in between the epithelial cells in the rete testis, epididymis, vas deferens, seminal vesicles and prostatic acini. Cells of the helper/inducer phenotype (Leu 3a+) were identified mainly within the interstitium of the epididymis and the prostate. B-lymphocytes (Leu 12+) were few in number and were mainly in the stroma of the prostate. In each organ the ratio of the T-cell subsets was determined and changes in this ratio were observed in epididymal and vasal biopsies from some infertile males. Finally, in testis biopsies from infertile men, suppressor/cytotoxic T-cells were demonstrated between the germinal epithelium and the fibrous tunica of the seminiferous tubules and as focal aggregates in the interstitium.

Antibodies, Monoclonal↗