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Biomedical subjects

A Stone

Publications and source records attributed to A Stone.

At least 91 records · Page 5Linked to original sources
PubMed1988

The inter-relationship between anchorage independence and tumorigenicity in early cultures of oral keratinocytes.

This study examines the expression of anchorage independence and tumorigenicity in early cultures of oral rat keratinocytes. The epithelial cell lines originated from the palatal and the lingual mucosa of rats that had been painted with the carcinogen 4-nitroquinoline N-oxide. The colony forming efficiency (CFE) in gel culture of the cell lines derived from five squamous cell carcinomas of the tongue and palate predominantly increased with passage in culture. Carcinoma-derived cell lines that had a relatively high CFE (greater than 2.5%) formed tumours when transplanted to athymic mice, but cells in which the CFE was less than 2.5% were non-tumorigenic. Keratinocytes from a dysplastic palatal lesion were immortal, anchorage dependent and non-tumorigenic. A lingual papilloma cell line consistently expressed a very low CFE but was tumorigenic at the higher culture passages. The results show that the routine passage of cells in culture leads to the emergence of the anchorage independent and tumorigenic phenotypes in keratinocytes of malignant origin and, further, suggest that anchorage independence and tumorigenicity may exist as distinct phenotypes, with anchorage independence preceding tumorigenicity.

Animals↗
PubMed1988

Transformation of oral keratinocytes in vitro by 4-nitroquinoline N-oxide.

Normal rat oral keratinocytes have been transformed with the carcinogen 4-nitroquinoline N-oxide (4NQO) in vitro. The morphology, growth characteristics, ability to grow without anchorage and tumorigenicity in athymic mice was examined in 12 selected cell lines. Each of the lines could be assigned to one of two general groups. The first group of cell lines although showing some morphological signs of transformation and the ability to be subcultured beyond passage 15 were not anchorage independent or able to form tumours in athymic mice. The second group of cell lines showed distinct signs of morphological transformation, could be serially subcultured without 3T3 feeder cells, were anchorage independent and tumorigenic in athymic mice. Anchorage independence was more common at higher passages and with increased 4NQO treatment and correlated well with a decreased reliance on 3T3 feeder cell support. The anchorage-independent phenotype was closely associated with the ability to form tumours in athymic mice. This same sequence of phenotypic changes has been demonstrated in rat oral keratinocytes after 4NQO treatment in vivo indicating that during carcinogenesis, cell populations progress through the same stages whether proliferation occurs in vitro or in vivo. There is some evidence to suggest, however, that the time interval between stages may be altered when carcinogenesis takes place in vitro.

4-Nitroquinoline-1-oxide↗
PubMed1986

Characterization of malignant rat keratinocytes in culture following the induction of oral squamous cell carcinomas in vivo.

An in vivo model of oral epithelial carcinogenesis in rats has been established successfully in cell culture. Oral carcinomas of the tongue and palate were induced in Sprague-Dawley male rats by painting their palates three times weekly for 7-8 months with 0.5% (w/v) 4-nitroquinoline-N-oxide. Oral keratinocytes from malignant and untreated control tissues were cultivated using 3T3 fibroblast support. Both the normal and malignant cells stained positively with an anti-human keratin polyclonal antibody but malignant keratinocytes were heterogeneous with regard to cell size, shape and intercellular packing, unlike the regular organization of the normal cultures. Malignant keratinocyte cultures differed markedly from their normal counterparts by an increase in their growth rate, the capacity for serial cultivation to the 25th passage (to date) and independence of 3T3 fibroblast support. In contrast, cultures established from healthy tissue showed signs of senescence usually by passage 4 and were totally reliant on 3T3 fibroblast support for growth. Malignant keratinocytes expressed anchorage independence when cultured in a semi-solid medium and gave rise to tumour formation in athymic mice. The development of this specialized cell culture system substantially increases the potential of the rat 4NQO model to investigate the pathogenesis of oral squamous cell carcinomas.

Animals↗
PubMed1985

The "lead-induced colic" syndrome in lead intoxication.

Lead has a multiplicity of biologic effects. The universal occurrence of lead accounts for the continuous appearance of new instances of human lead poisoning. The most common and one of the earliest manifestations of lead intoxication in the adult is so-called lead-induced colic, which is a syndrome with a multiplicity of clinical patterns and at least three possible different pathogenic mechanisms. It may be caused by changes in the visceral smooth muscle tone secondary to the action of lead on the visceral autonomic nervous system, lead-induced alterations in sodium transport in the small-intestinal mucosa, and lead-induced interstitial pancreatitis. It should be considered in the differential diagnosis of abdominal pain of obscure etiology and whenever a disparity is observed between the symptoms and the abdominal findings in a patient with abdominal pain, especially in the presence of a history of occupational exposure to lead.

Abdominal Muscles↗
PubMed1985

Cold protection and heat enhancement of doxorubicin skin toxicity in the mouse.

A series of experiments were performed in a BALB/c mouse model to evaluate the efficacy of topical heating and cooling on doxorubicin (DOX) ulceration of the skin. Unanesthetized mice were administered a dose of 0.05 mg or 0.5 mg of DOX intradermally, followed by topical heating (43 degrees C-44 degrees C) or cooling (8 degrees C-10 degrees C) of the skin area for up to 1 hour. DOX disposition from skin and plasma was studied by high-pressure liquid chromatography in both cooled and uncooled groups of animals. Human tumor clonogenic cells were exposed to DOX for 1 hour at different temperatures to determine the direct effect of heat and cold on DOX-induced lethality in vitro. Skin temperature of 17 degrees C +/- 2.3 degrees C was achieved with cooling and skin temperature of 38.5 degrees C +/- 1.2 degree C was achieved with heating, compared to control intradermal skin temperature of 32 degrees C +/- 0.5 degree C. Local heating caused duration-dependent DOX lethality: 20% after 20 minutes, 40% after 45 minutes, and 80% after 1 hour. There were no deaths in the control groups. A 20% lethality rate was constant in the cooled groups. Skin lesions were approximately fourfold larger in the heated groups receiving 0.5 mg of DOX (P less than 0.05). In contrast, the application of cold significantly reduced intradermal DOX skin toxicity following the lower DOX dose of 0.05 mg (P less than 0.05). There was no consistent benefit for cooling beyond a 45-minute duration, which achieved maximal protection against ulceration. Pharmacokinetic studies of DOX disposition in skin and blood failed to show a significant difference for total tissue concentrations or plasma levels between cooled and uncooled animals. However, clonogenic human tumor cells (HEC-1A endometrial cells) did demonstrate significantly reduced DOX effects when exposed to the drug at reduced temperatures. These results confirm the biologic efficacy of local cooling and clearly contra-indicate the use of local heating to treat inadvertent DOX extravasations in the clinic. Instead, cold should be applied immediately and maintained for 45 minutes or longer to reduce or prevent serious DOX skin ulcerations in patients.

Animals↗
PubMed1984

Measurement of systolic time intervals during exercise using inductive plethysmography.

Measurement of systolic time intervals (STI) provides a noninvasive assessment of cardiac function in resting subjects. However, large motion artifacts often limit their application during exercise. To improve such measurements, we employed a new lightweight carotid arterial pulse transducer and minimized the artifacts by computerized signal averaging. The carotid pulse was recorded with an inductive plethysmographic transducer band (CIP) wrapped around the neck. STI derived from these measurements were compared to standard measurements from a funnel-shaped cup attached to the neck and connected to a pressure transducer (CUP) in 12 normal subjects at rest and with graded bicycle ergometry. To compare the techniques, CIP and CUP signals, together with the EKG and phonocardiogram, were connected separately to two microcomputer systems. The systems were triggered from the EKG and averaged the signals over 16 or 32 heart beats. Semi-automatic analysis of the averaged signals provided estimates of left ventricular ejection time (LVET), pre-ejection period (PEP) and electromechanical systole (QS2). Motion artifact levels of the unprocessed signals were similar with both CIP and CUP methods but were greatly reduced by signal averaging. All LVET values using CIP fell within 10% of CUP values. 85% of PEP values using CIP were within 20% of CUP values. Increasing exercise loads produced appropriate decreases in QS2, LVET, PEP and PEP/LVET consistent with increased myocardial contractility. The CIP proved comfortable to wear and did not require critical positioning as did the CUP. Measurement of STI complements exercise pulmonary testing with useful information of cardiac function.

Adult↗
PubMed1979

A study of transfer factor for opportunistic infections in cancer patients.

Although supportive care during therapy of patients with malignancies has improved, infection remains the major cause of death in these patients. The problem of "opportunistic" infections is becoming more apparent as better antibiotics are found. The control of these infections depends in part on mechanisms of cell-mediated immunity. It has been demonstrated that delayed-type hypersensitivity can be transferred from one person to another. Therefore, we used transfer factor in the treatment of 15 patients, most with leukemia, who had fungal, viral, or mycobacterial infections that were not responding to conventional therapy. Seven of ten evaluable patients had therapeutic control of their infections while receiving transfer factor. Transfer factor appears to have contributed to these clinical improvements and is a modality of treatment that deserves further investigation.

Adolescent↗
PubMed1979

Mandibular odontogenic infection with serious complications.

Orbital cellulitis usually begins as an infection of the paranasal sinuses. While a small percentage of cases are of dental origin, these usually involve the maxillary teeth. In the case reported here orbital cellulitis originated from an infection in the mandible and spread through the pananasal sinuses, deep facial circulation, and orbital tissues, resulting in unilateral blindness. Principles of management and possible pathways for the spread of the infection are discussed.

Adult↗