Biomedical subjects

M G Cook

Publications and source records attributed to M G Cook.

At least 73 records · Page 4Linked to original sources

PubMed1991

A comparative study of proliferation indices and ploidy in dysplastic naevi and malignant melanomas using flow cytometry.

Cell proliferation indices and DNA content have been determined in 18 intradermal naevi, 40 dysplastic naevi and 16 superficial malignant melanomas (less than 0.76 mm depth of invasion) using flow cytometry. In this study, proliferation indices of intradermal naevi and dysplastic naevi were not significantly different from each other. Abnormalities of DNA ploidy were not identified in the intradermal naevi or dysplastic naevi; whereas three of the malignant melanomas were aneuploid. In addition, cellular proliferation was increased within the group of malignant melanomas, in comparison with the naevi. This study has found no evidence to indicate that sporadic dysplastic naevi were more likely than intradermal naevi to transform to malignant melanoma, when objective criteria were employed. However, dysplastic naevi could be distinguished from some early malignant melanomas by absence of aneuploidy and by low cell proliferation indices.

Adolescent↗

PubMed1991

Morphometric evaluation of the contractile apparatus in primary cultures of rabbit cardiac myocytes.

Rabbit cardiac myocytes remain quiescent for more than 1 month when cultured at low density. During this period, myofibrillar volume density declines sixfold as myofibrils are disassembled or degraded and are replaced by actin and alpha-actinin-positive, myosin-negative structures that resemble myofibrils but lack thick filaments. Such structures are termed minute myofibrils. The length of the sarcomeres in these altered myofibrils is significantly less than length values obtained from freshly isolated heart cells or from contracting myocytes. A number of high density cultures develop spontaneous, synchronous contraction during the second week of culture. Myofibrillar volume density is stabilized when beating begins, and no further decline is observed in the succeeding weeks of culture. Such contracting myocytes display myofibrils typical of normal heart with no visible evidence of minute myofibrils. The volume density of the transverse tubular system also declines significantly in both beating and nonbeating myocytes, and its reduction appears more closely correlated with cell spreading than with beating per se. No quantitative changes in volume density of mitochondria or sarcoplasmic reticulum could be documented, but the structural organization of the sarcoplasmic reticulum seems to be greatly influenced by the physiological state of the heart cell. The present observations document the importance of mechanical factors in regulating the integrity of the contractile apparatus in cardiac myocytes and emphasize the utility of the cultured heart cell to directly investigate structure-function relations in individual myocytes.

Animals↗

PubMed1991

Benign breast disease: the relationship between its histological features and risk factors for breast cancer.

Associations between histologically defined proliferative, but benign, epithelial disorders of the breast and risk factors for breast carcinoma were examined in 568 patients whose breast biopsies were submitted consecutively to the laboratory. Some disorders were associated with multiparity. Blunt duct adenosis was associated with a family history of breast cancer. Apart from a positive association with fibroadenoma, use of oral contraceptives was not associated with any proliferative lesion. Proliferative epithelial lesion changes were not associated with other aspects of obstetric or gynecological history.

Adult↗

PubMed1990

Relation between severity and extent of precancerous lesions in the postoperative stomach.

The relation between the severity and extent of precancerous lesions in a precancerous condition of the stomach was assessed, to find a means of reducing the endoscopic workload required for the detection of such lesions. 87 subjects who had had gastric surgery for peptic ulcer more than 20 years ago underwent gastric endoscopy and biopsy. Severity of dysplasia correlated with its extent. Severity of intestinal metaplasia correlated with its extent and with severity of dysplasia. Type of operation, but not sex or type of ulcer, was the factor most strongly associated with dysplasia. Previous Billroth II operations were more strongly associated with occurrence of dysplasia (85%) than were other operations. In patients with previous Billroth II operations, moderate and severe dysplasia were commoner around the stoma (37%) than in the body (10%). These findings indicate that there is a relation between the severity and extent of precancerous lesions, which suggests that patients with dysplasia have widespread gastric mucosal instability. They also indicate that, if endoscopic screening is limited to Bilroth II subjects and if biopsies are limited to the stoma, endoscopic workload can be reduced by 85%, with only a small reduction (15%) in detection of moderate and severe dysplasia.

Biopsy↗

PubMed1990

A case-control study of diet and benign proliferative epithelial disorders of the breast.

Benign proliferative epithelial disorders (BPED) of the breast are conditions which, although not proven precursors of breast cancer, are strongly associated with increased risk of this disease. In a case-control study conducted in Adelaide, South Australia, we investigated the association between dietary factors and risk of BPED. The study involved 383 cases of biopsy-confirmed BPED, 192 controls whose biopsy did not show epithelial proliferation, and 383 unbiopsied community controls matched to cases on age and area of residence. When cases were compared with community controls, there was little variation in the risk of BPED across levels of daily intake of energy, protein, and fat, but there was some suggestion of inverse associations with daily intake of retinol, beta-carotene, and fiber; in contrast, with biopsy controls as the comparison group, risk of BPED increased with increasing energy and fat intake but varied little with retinol, beta-carotene, and fiber intake. The results of this study provide additional evidence against roles for dietary energy and fat intake in the etiology of breast cancer. However, further studies of diet and BPED should be conducted in populations surveyed cross-sectionally for breast changes, in an attempt to limit or avoid the selection and misclassification biases to which studies of putative precursor lesions are susceptible.

Adult↗

PubMed1990

Morphological analysis of contracting and quiescent adult rabbit cardiac myocytes in long-term culture.

Isolated rabbit ventricular cardiac myocytes adapt readily to primary culture. As the myocytes spread and flatten over the culture substratum, the myofibrillar apparatus retains a "rod-like" orientation. Development of contractile activity is crucial in the maintenance of the integrity of the myofibrillar apparatus during prolonged culture. Myocytes that fail to beat display morphological indications of atrophy; conversely, myocytes that commence beating show no such morphological signs of myofibrillar disorganization. The subcellular organization of other elements of the contractile apparatus, including the transverse tubular system and the sarcoplasmic reticulum, retain their structural relationship with the myofibrils in beating myocytes but not in quiescent cells. Cultured adult myocytes represent an important model to investigate the influence of mechanical factors on the organization and maintenance of the adult cardiac phenotype.

Animals↗

PubMed1990

Lymphatics in primary cutaneous melanoma.

Using Ulex europaeus I lectin (UEA1) to demonstrate endothelial cells, we have previously shown that frequency of capillary invasion correlates closely with maximum tumor thickness in primary cutaneous melanoma. UEA1 demonstrates both vascular and lymphatic capillaries; however, only vascular capillaries possess basement membranes. In order to ascertain whether these capillaries were lymphatic or vascular, we employed a double staining technique, using UEA1 in conjunction with a monoclonal anti-type IV collagen antibody. We studied 21 primary cutaneous melanomas. Seven of the 21 included lymphatic capillaries, while 14 did not. These lymphatic capillaries were very sparse and appeared to be residual dermal lymphatics rather than a result of lymphangiogenesis. Lymphatic permeation by melanoma was not seen in any of the tumors studied. There was no apparent association among tumor thickness, level of invasion, growth phase, necrosis, regression or mitotic index, and presence of lymphatics within the melanomas. Although scanty lymphatics are present in some primary cutaneous melanomas, this study does not suggest that lymphatic permeation plays a major role in the spread of melanoma to locoregional lymph nodes.

Humans↗

PubMed1990

Effect of incisional biopsy on subsequent histology of melanocytic naevi.

We examined the effect of incisional biopsy on the subsequent histology of 15 benign melanocytic naevi. In all cases the histology of the residual lesion within the second specimen was unchanged apart from the presence of a surgical scar, and in general the definitive excision specimen showed a reduction in melanocytes at the dermo-epidermal junction overlying the scar. In no case were there any features suggestive of melanoma.

Biopsy↗

PubMed1990

Hidradenitis suppurativa: a disease of follicular epithelium, rather than apocrine glands.

A retrospective study was made of the histopathology of axillary skin excised from 12 patients with hidradenitis suppurativa. In the majority of cases (10 out of 12), squamous epithelium-lined structures, in the form of cysts or sinuses were identified in the dermis. Laminated keratin was present in all these structures and half of the cysts also contained hair shafts, suggesting that they are derived from hair follicles. Only a small proportion of cases (4 out of 12) displayed inflammation in apocrine glands, and in these the inflammation was also seen around eccrine glands, hair follicles and the epithelium-lined structures. However, in cases where the epithelium of the 'cysts' was disrupted, the inflammatory infiltrate appeared to be centred around these areas. These observations suggest that the squamous epithelium-lined structures, which probably represent abnormal dilated hair follicles, are a more constant diagnostic feature in hidradenitis suppurativa than inflammation of apocrine glands which appears to be a secondary phenomenon.

Apocrine Glands↗

PubMed1990

Epidermal melanocytes adjacent to melanoma and the field change effect.

The presence of a field change, affecting epidermal melanocytes in the skin surrounding melanomas, has been cited as a justification for performing radical excision of these lesions. Twenty-five consecutive re-excisions of melanoma specimens were examined and melanocytes per 100 keratinocytes counted continuously across the width of each, in order to ascertain whether melanocyte counts decreased from the centre to the periphery, as would be expected if there were a field change effect associated with the tumour. Melanocyte counts did not appear to diminish with increasing distance from the tumour site and were within the range seen in a previous study in which we demonstrated increased numbers of basal melanocytes and melanocyte atypia in sun-exposed skin from a control population. Melanocyte atypia of a mild degree was present in five of the 25 cases studied, but in no case was this greater than that observed in sun-exposed forearm skin. We therefore suggest that the 'field change effect' in epidermal melanocytes adjacent to melanoma could be a result of chronic sun exposure alone.

Adult↗

PubMed1990

Dysplastic naevi--an alternative view.

The diagnosis of dysplastic naevus is in danger of falling into disuse in response to the continuing dispute as to its definition. This review tries to show that the lesion can be defined using histological and clinical criteria but that the individual features are not, by themselves, peculiar to dysplastic naevi. They are shared, in varying degrees, by other benign melanocytic naevi and by melanoma. The significance of these similarities is explained on the basis of the maturation of ordinary naevi and degrees of deviation from that common path. The recognition of severely aberrant differentiation in the form of classic dysplastic naevus is worthwhile, since in the appropriate clinical context and particularly in association with a family history of melanoma, it confers a very high risk of developing melanoma.

Dysplastic Nevus Syndrome↗

PubMed1990

Use of isolated adult myocytes to evaluate cardiotoxicity. I. Sugar uptake and protein synthesis.

The usefulness of isolated adult cardiac myocytes, both in suspension and in culture, as a model system for measuring cardiotoxicity is evaluated. It has been suggested that isolated adult myocytes should preferably be cultured for such experimentation, as this restores the cells to a physiological preference for fatty acids as a substrate rather than glucose. We show here that the restoration of Ca2+ to cells immediately after isolation results in an artificially enhanced glucose metabolism, as measured by an elevated rate of deoxyglucose uptake. Early restoration of Ca2+ during cell isolation, on the other hand, results in cells with a normal low level of deoxyglucose uptake. We, thus, conclude that cells can be ready for valid toxicity studies immediately after isolation, without the need for culture. The culture of adult feline ventricular cells is also described. These cells, like rabbit but unlike rat, are particularly promising for toxicity studies because they remain quiescent in culture and do not round up. On exposure to norepinephrine, they beat spontaneously and increase their rate of protein synthesis.

Animals↗

PubMed1989

Accuracy in clinically evaluating pigmented lesions.

OBJECTIVE: To determine the ability of three doctors experienced in managing melanocytic lesions to diagnose correctly melanoma, dysplastic naevi, and various benign pigmented lesions. DESIGN: Independent clinical evaluation and histopathological assessment. SETTING: Pigmented lesion clinic, which patients attend without an appointment for early diagnosis of melanoma. PATIENTS: 86 Patients with lesions that were judged to be benign by at least one of the three doctors. INTERVENTIONS: The lesions were excised under local anaesthesia and sent for histopathological examination in coded bottles without clinical details. MAIN OUTCOME MEASURE: Comparison of clinical with histopathological diagnosis for each lesion. RESULTS: A total of 120 lesions were evaluated by at least two of the three doctors. The histopathological diagnoses were made by the same pathologist. The overall sensitivity (diagnostic accuracy) for the three doctors for all types of lesion was 50%. Of the 39 dysplastic naevi, only 19 were identified correctly by all observers, and a further 24 banal lesions were wrongly diagnosed as dysplastic by at least one doctor. Particular difficulty was experienced with small (less than 5 mm), flat lesions, which can be banal or potentially malignant. CONCLUSIONS: Critical diagnosis and management decisions concerning pigmented lesions should always be based on a combination of clinical and histopathological assessments and the history of the patient.

Diagnosis, Differential↗

PubMed1989

Alcohol consumption and risk of benign proliferative epithelial disorders of the breast in women.

Many studies have shown a positive association between alcohol consumption and risk of breast cancer. Benign proliferative epithelial disorders (BPED) of the breast are conditions which, although not proven precursors of breast cancer, are strongly associated with increased risk of this disease. The association between alcohol consumption and risk of BPED was examined in a case-control study conducted in Adelaide, South Australia. The study involved 383 cases with biopsy-confirmed BPED, 192 controls whose biopsy did not show epithelial proliferation, and 383 unbiopsied community controls individually matched (I:I) to cases on age and area of residence. When cases were compared with community controls, the unadjusted relative risk of BPED for drinkers versus non-drinkers was 0.9 (95% CI 0.6-1.3), and the corresponding relative risk derived from comparing cases with biopsy controls was 1.0 (95% CI 0.6-1.4); these estimates were not altered after adjustment for potential confounding. Variation in risk of BPED across levels defined in terms of daily total alcohol intake, and in terms of daily alcohol intake from individual beverages, was mostly insubstantial and not dose-dependent. Also, there was little variation in risk with age at first drink, or by current drinking status, and risk of BPED in association with alcohol consumption did not increase with severity of cytologic atypia. Despite the absence of an association in this study, further investigation is warranted, since it may provide opportunities for the prevention of BPED and of breast cancer.

Adolescent↗

PubMed1989

Methylxanthines and benign proliferative epithelial disorders of the breast in women.

The relationship between methylxanthine intake (caffeine, theobromine and theophylline) and risk of benign proliferative epithelial disorders (BPED) of the breast was examined in a case-control study conducted in Adelaide, South Australia. The study involved 383 cases with biopsy-confirmed BPED, 192 controls whose biopsy did not show epithelial proliferation, and 383 unbiopsied community controls individually matched to cases on age and area of residence. Overall, there was relatively little variation in risk of BPED with total methylxanthine intake, or with intake of caffeine or theophylline, while there was a positive association between theobromine intake and risk of BPED, but only when cases were compared with biopsy controls. Total methylxanthine intake was positively associated with risk of BPED showing severe atypia, but the trend in risk was statistically significant only when community controls formed the comparison group. These data do not provide strong support for an association between methylxanthine intake and risk of BPED.

Adolescent↗

PubMed1989

Vascular invasion in malignant melanomas. An independent prognostic variable?

The role of vascular invasion as a prognostic indicator in melanoma has not been fully evaluated, mainly due to difficulty in differentiating between capillaries and artefactual spaces caused by shrinkage in routine histological sections. However, immunohistochemical staining using Ulex europaeus I (UEA-I) permits accurate identification of tumor capillaries, thus facilitating recognition of vascular invasion. Sixty-six primary cutaneous melanomas were included in this study. Sections of each case were stained with UEA-I; then, vascular invasion at the level of the tumor capillary bed was sought. Hematoxylin-and-eosin-stained sections were reviewed; the thickness of each lesion was measured and the level of invasion and the growth phase of the tumors were also assessed. The frequency of vascular invasion was found to increase with increasing tumor thickness and with increasing level of invasion. Vascular invasion was seen in only one of 29 horizontal growth phase melanomas, whereas it was identified in 28 of 37 vertical growth phase tumors. Although these results would seem to indicate that vascular invasion within melanomas is unlikely to be an independent prognostic variable, they may partly explain the deteriorating prognosis associated with increasing tumor thickness. They also lend support to the concept of "horizontal" and "vertical" growth phase in melanoma.

Capillaries↗

PubMed1989

The value of nucleolar organizer region staining in the differential diagnosis of borderline melanocytic lesions.

The technique of silver (Ag) staining of nucleolar organizer region-associated proteins (AgNORs) has been shown to be of value in differentiating between benign and malignant cells. We have studied 33 borderline melanocytic lesions, in which a diagnosis of melanoma had been seriously considered, in order to assess the value of this technique in a commonly encountered diagnostic situation. We found that benign naevus cells possessed single compact or granular AgNORs, whereas some malignant melanocytes possessed large, often loosely arranged groups of AgNORs. However, the pattern of AgNORs observed in melanocytes of some atypical but benign lesions was also seen in some melanomas. The differential diagnosis of borderline melanocytic lesions is not clarified by use of the AgNOR technique.

Diagnosis, Differential↗

PubMed1989

Dysplastic naevi.

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Dysplastic Nevus Syndrome↗