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Biomedical subjects

M Fox

Publications and source records attributed to M Fox.

At least 199 records · Page 11Linked to original sources
PubMed1984

Splenic siderosis and parenteral iron dextran in maintenance haemodialysis patients.

The histological features of 40 spleens surgically removed from maintenance haemodialysis patients are reported. Twenty-four of the 40 (60%) showed massive iron loading and a significant direct correlation was found between iron loading and the amount of intravenous iron dextran administered. Since parenteral iron dextran appears to be a major factor in causing iron overload in haemodialysis patients its use as a method of iron replacement in these patients would appear inappropriate.

Blood Transfusion↗
PubMed1984

Effect of 12-O-tetradecanoylphorbol-13-acetate on selection of drug-resistant phenotypes in rodent cells.

The effect of the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on the selection of drug-resistant phenotypes in hamster and mouse cells has been studied. TPA increased considerably the incidence of methotrexate (MTX)-, N-(phosphonacetyl)-L-aspartate- and cadmium-resistant 3T6 and 3T3 mouse cell clones, but it had little effect on V79 and CHO hamster cells. The MTX-resistant V79 hamster cell clones, selected with or without TPA, lost their resistance within 15 cell cycles, however, 50% of the 3T6 mouse cell clones selected and maintained in the presence of TPA preserved their resistance for more than 15 cell cycles. A number of the MTX-resistant 3T6 clones overproduced dihydrofolate reductase enzyme; however, their frequency was lower among the clones selected in the presence of TPA.

Animals↗
PubMed1983

Rat pancreas allotransplantation: a short term comparison of rejection patterns with different methods of exocrine drainage.

Pancreas transplantation has been performed in the rat to study the effect on rejection of duct ligation, duct obliteration and duct open intraperitoneal drainage. On day six, an acceleration of graft damage was seen in the duct ligated and obliterated allografts compared to the duct open group. However, by day 11, rejection was complete in all three groups. In comparison with pancreatic isografts, the histological diagnosis of rejection can be difficult to define, particularly in the duct ligated and obliterated groups. The most useful criterion was the localisation of the cellular infiltrate to the walls of small veins and within the islet of Langerhans.

Animals↗
PubMed1983

Molecular evolution of the human adult alpha-globin-like gene region: insertion and deletion of Alu family repeats and non-Alu DNA sequences.

Previous heteroduplex studies have revealed extensive sequence homology between the two human adult alpha-globin-like genes (alpha 2 and alpha 1) and their flanking regions. These homologous regions, which are interrupted by two blocks of nonhomology, each span approximately 4 kilobases [Lauer, J., Shen, C.-K. J. & Maniatis, T. (1980) Cell 20, 119-130]. We have determined 3 kilobases of DNA sequences within and flanking the nonhomologous blocks of these two tandem duplication units. A total of three Alu family repeats has been identified. Two of them are approximately 300 base pairs long and define the 3' ends of the first homology blocks. The third Alu family member is a 600-base-pair-long sequence consisting of two monomeric Alu members arranged in a head-to-tail fashion. It is located in the 3' portion of the first block of nonhomology in alpha 2-gene-containing unit. We present direct evidence that this dimeric Alu sequence was inserted at a staggered break. The second nonhomology block is the result of insertion or deletion of a 224-base-pair sequence. From these data and the calculation of sequence divergence, we propose a history for the evolution of the human adult alpha-globin-like gene region. We also suggest that DNA insertion elements may disrupt gene correction processes in the two duplication units containing alpha 2- and alpha 1-globin genes.

Adult↗
PubMed1983

Differential responses of nascent DNA synthesis and chain elongation in V79 and V79/79 cells exposed to u.v. light and chemical mutagens.

DNA repair after u.v., N-methyl-N-nitrosourea (MNU) and ethylmethane sulphonate (EMS) in Chinese hamster V79 cells and the mutagen sensitive derivative V79/79 was investigated by measurement of five parameters: production of strand breaks in template DNA, incorporation of [3H]TdR, semi-conservative and repair synthesis, molecular weights of pulse labelled DNA after mutagen exposure (nascent synthesis) and molecular weights of DNA pulse labelled and chased after mutagen exposure (elongation and ligation). Equal template strand breakage was evident in both cell lines immediately after MNU and EMS exposure and by 4-5 h after MNU the extent of fragmentation was greater in V79/79 cells. After u.v. irradiation template fragmentation was evident in V79/79 but not in V79 cells, even though V79/79 cells failed to excise cyclobutane dimers and repair synthesis was demonstrable in V79 cells but not in V79/79 cells after exposure to all three mutagens. The rate of incorporation of [3H]TdR during semi-conservative DNA synthesis was inhibited equally in a dose dependent manner after u.v. and MNU exposure; incorporation by V79/79 cells was inhibited to a greater extent than by V79 cells after EMS exposure. Nascent DNA synthesis was suppressed more in V79/79 cells than in V79 cells after u.v. but to similar extents in both cell lines after MNU and EMS treatment. Pulse chase experiments indicated a lower rate of elongation of nascent DNA in V79/79 cells after MNU and u.v. exposure but little difference was detectable after EMS.

Animals↗
PubMed1983

The role of suppression of DNA synthesis and inhibition of cell cycle progression in cellular sensitivity to alkylation damage.

A u.v. sensitive Chinese hamster cell line V79/79 has been shown to be also more sensitive to methyl methanesulphonate (MMS) and nitrogen mustard (HN2) exposure than wild-type V79 cells. A comparison of the effects of the two alkylating agents on DNA synthesis measured by [3H]thymidine (TdR) incorporation into whole cells and by alkaline sucrose gradient sedimentation 14C-labelled template and of pulse labelled DNA revealed no significant differences between the responses of the two cell lines. The effects of a range of doses of both drugs on the rate of progress through the cell cycle was compared using cytofluorimetry. The more sensitive V79/79 cells failed to show a significant delay in progress through the cell cycle even at the highest doses tested (0.2 microM HN2 and 2.0 mM MMS). In contrast, V79 cells showed a marked S phase delay in response to both HN2 and MMS exposure. The possible relationships between failure to delay cell cycle progression, and cellular sensitivity are discussed.

Animals↗
PubMed1983

Pancreatic transplantation in the rat. Long-term study following different methods of management of exocrine drainage.

A major problem in pancreas transplantation is the management of exocrine drainage. Isotransplantation has been performed in streptozotocin-induced diabetic rats using a microsurgical technique, and four methods of exocrine drainage have been compared over a nine-month period. The duct system was ligated, left open to drain into the peritoneal cavity, or obliterated with latex or with Ethibloc I occlusion gel. Biochemical follow-up included determinations of serum glucose concentration, intravenous and oral glucose tolerance tests (GTTs), and insulin assays. Histological studies were performed at 1 and 9 months posttransplant. All animals became normoglycemic after the operation. Although 25 out of 28 remained normoglycemic throughout the period of study, oral GTTs performed at six months indicated impaired endocrine function in some of the ligated, freely draining, and Ethibloc I-obliterated animals. Latex-obliterated grafts showed normal oral GTTs up to 9 months postoperatively. Intravenous GTTs showed impairment of endocrine function in all groups, but this was least evident in the latex-obliterated rats. These changes were supported by the peak serum insulin levels during the GTTs. Histologically, long-term ligated, freely draining, and Ethibloc I-obliterated pancreas grafts showed similar degrees of exocrine degeneration, fibrosis, and disruption of islets of Langerhans. In contrast, long term latex-obliterated pancreas grafts demonstrated minimal exocrine tissue and intact islets.

Animals↗
PubMed1983

Cold storage of the pancreas with a view to preservation of islet cell function following transplantation.

Three solutions, hyperosmolar citrate, modified Collins' C2, and Sacks' II solutions were compared as media for cold storage preservation (arterial infusion and subsequent cold storage in the same medium at 0-4 C) of the rat pancreas with a view to preservation of endocrine function. Pancreatic isotransplantation was performed following cold ischemic intervals of 0, 24, 30, and 36 hr, into streptozotocin-induced diabetic recipients. Results were assessed by normoglycemic survival and insulin response, together with K values following i.v. glucose tolerance tests at 3 months postoperatively; 24-hr preservation was achieved with equal success using modified Collins' C2 solution or hyperosmolar citrate-but not with Sacks' II solution. Preservation for 30 hr was consistently successful using modified Collins C2 solution only, but the period could not be extended with success to 36 hr. Hypoglycemia and hyperinsulinemia occurred 24 hr postoperatively in the majority of animals receiving grafts stored in Sacks' II solution, but to a much lesser extent using modified Collins' C2 and hyperosmolar citrate. This was also temporarily seen in grafts stored for 36 hr in modified Collins C2 solution. At 3 months postoperatively after 30 hr cold ischemia, i.v. glucose tolerance tests showed the hyperosmolar citrate cold-stored grafts had lower K values and significantly reduced insulin responses compared with grafts stored in modified Collins' C2 solution. The modified Collins' C2 solution proved to be the most effective of the three solutions tested.

Animals↗
PubMed1983

Investigation of the cell cycle response of normal and Fanconi's anaemia fibroblasts to nitrogen mustard using flow cytometry.

Cell survival has been measured in normal and Fanconi's anaemia (FA) human fibroblasts after treatment with the bifunctional alkylating agent, nitrogen mustard (HN2). Two FA cell lines exhibited 6- to 10-fold greater sensitivity than the normal cell line. Flow cytometry was used to investigate the effects of HN2 on cell cycle progression of normal and FA cells. After 0.1 microgram/ml HN2 (surviving fraction, s.f. = 0.8) normal cells exhibited an S phase accumulation within 6 h, followed by a transient G2 delay. At higher doses of HN2, the S phase delay became more pronounced and there was considerably greater accumulation of cells in G2. HN2 at 0.01 microgram/ml (s.f. = 0.8) induced no detectable S or G2 delay in FA cells. A higher dose, 0.1 microgram/ml (s.f. = 0.13 and 0.29), again induced no S phase delay, but a gradual accumulation of cells in G2 was observed up to 78 h after treatment. The presence of an S phase delay in normal cells after HN2 treatment may be important in allowing time for DNA repair before completion of DNA synthesis. The absence of such a delay in FA cells suggests that an inability to delay S phase traverse in response to DNA damage from bifunctional alkylating agents may contribute to the sensitivity of FA cells to such drugs.

Anemia, Aplastic↗
PubMed1983

A comparison of incremental exercise tests during cycle and treadmill ergometry.

We evaluated a short-duration maximum exercise test by comparing a 15-s incremental exercise protocol with a 1-min incremental method. Twenty normal men and women were studied using cycle and/or treadmill ergometry. In subjects tested on both exercise devices, anaerobic threshold and maximal oxygen uptake (VO2max) were higher for both protocols on the treadmill than on the cycle ergometer (P less than 0.001). However, when the 15-s and 1-min tests were compared using the same device (treadmill or cycle), there were no significant differences between protocols in anaerobic threshold or maximum exercise values of minute ventilation, respiratory rate, tidal volume, VO2max, oxygen pulse, and peak expiratory flow rate. Linear regression analyses indicated differences between the 15-s and 1-min protocols when cardiopulmonary measurements were related to power; however, the two protocols were comparable when cardiopulmonary data were related to oxygen uptake. Comparisons between protocols or between exercise devices were not systematically different in large vs small individuals, or in men vs women. Short-duration incremental exercise tests appear to be reliable, practical methods for assessing exercise performance in normal individuals.

Exercise Test↗
PubMed1983

Fatality rates and regulatory policies in bituminous coal mining, United States, 1959-1981.

In the eleven years prior to the passage of the Federal Coal Mine Health and Safety Act of 1969, fatality rates changed little for underground miners and were increasing for surface miners. Following implementation of the 1969 Act, both rates decreased. Beginning in 1979, and continuing into the first six months of 1982, both rates increased. These associations suggest that current relaxation of regulations and policies for coal mine safety are unwarranted.

Accident Prevention↗
PubMed1983

Who goes to a natural therapist? Why?

This survey investigated the understanding and attitudes of 38 patients using alternative therapies and their reasons for doing so. Although the small sample could bias the results, the article opens the subject for discussion and could serve as a model for a larger survey from which more valid conclusions could be drawn.

Acupuncture Therapy↗
PubMed1983

Effect of tumor promoter 12-O-tetradecanoylphorbol-13-acetate on recovery of methotrexate-, N-(phosphonacetyl)-L-aspartate-, and cadmium-resistant colony-forming mouse and hamster cells.

The effect of the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and its nontumor promoting derivative 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate on the frequency of mouse and hamster cells resistant to methotrexate (MTX), N-(phosphonacetyl)-L-aspartate, and cadmium has been examined. TPA alone at concentrations up to 1.0 microgram/ml had no significant effect on the plating efficiency of either mouse or hamster cells. Exposure of 3T3 and 3T6 mouse and V79 and Chinese hamster ovary cells at low density to the 3 compounds in the presence of TPA (0.1 microgram/ml) did not result in any increase in the recovery of resistant colonies. When plated at high density, exposure to drug selection in the presence of TPA resulted in a 3- to 10-fold increase overall in the incidence of MTX-, N-(phosphonacetyl)-L-aspartate-, and cadmium-resistant mouse cells. However, an increase greater than 3-fold was not observed in hamster cells exposed to drug plus TPA under the same conditions. 4-O-Methyl-12-O-tetradecanoylphorbol-13-acetate had no significant effect on the frequency of MTX-resistant cells. Seventy V79 cell clones surviving MTX (200 to 400 nM) alone and 79 surviving MTX plus TPA were isolated and retested for resistance to MTX. None were stable. In contrast, 6 out of 42 mouse colonies isolated from MTX alone and 55 out of 99 isolated from MTX plus TPA showed stable resistance on retesting in MTX. The implications of these results in relation to possible mechanisms of tumor promotion are discussed.

Animals↗
PubMed1982

An association between neonatal severe primary hyperparathyroidism and familial hypocalciuric hypercalcemia in three kindreds.

Four cases of neonatal severe primary hyperparathyroidism occurred in three families; familial hypocalciuric hypercalcemia was present in each kindred. The diagnosis of familial hypocalciuric hypercalcemia was based on the following features; hypercalcemia in many relatives (eight to 16 per kindred), without other features of the multiple endocrine neoplasia syndromes; recognition of hypercalcemia before the age of 10 in one to three relatives; hypocalciuric hypercalcemia in all relatives tested (five to 14 per kindred); and abnormal serum calcium levels despite parathyroidectomy in all additional relatives (one to five per kindred) undergoing this operation. The association of two uncommon syndromes (neonatal severe primary hyperparathyroidism and familial hypocalciuric hypercalcemia) in these kindreds suggests that the two syndromes share a common genetic cause within each kindred.

Adolescent↗
PubMed1982

Relative sensitivity of V79 and V79/79 cells to spontaneous and induced mutation to 6-thioguanine and ouabain resistance.

The relative responses of V79 and V79/79 cells to mutation to 6-thioguanine (6TGR) and ouabain resistance (OUAR) have been compared in unmutagenized cells and after exposure to ethyl methanesulphonate (EMS), N-methyl-N-nitrosourea (MNU) and ultraviolet light. In the V79/79 cell line, the spontaneous frequency of 6TGR colonies but not of OUAR colonies was enhanced compared to that in V79 cells. This appears to be the result of a reduced growth rate and plating efficiency of V79/79 cells and does not reflect a real difference in spontaneous mutability. V79/79 cells were more sensitive than V79 to the cytotoxic effects of all three mutagens, but induced mutation by UV, EMS and MNU to 6TGR was similar in the two cell lines. The lack of a differential response for induced mutation to 6TGR may reflect: (a) differences in selective stringency of thioguanine in the two cell lines, and (b) the greater susceptibility of V79/79 cells to induced chromosome damage. The relative mutability of the two cell lines to OUAR was dependent on the mutagen used. V79 cells were significantly more mutable than V79/79 cells after MNU exposure, but the two cell lines were similar in sensitivity to EMS-induced mutation. After UV-irradiation, however, V79/79 cells were morem utable than V79 cells. The differential response of the two cell lines to MNU suggests that O6-methylguanine is potentially mutagenic in V79 cells but is both potentially lethal and potentially mutagenic in the more sensitive V79/79 cells. The absence of a differential response to EMS-induced mutagenesis suggests that methylated and ethylated bases are repaired differently in Chinese hamster cells. The hypermutability of V79/79 cells by UV-irradiation indicates that thymine dimers are potentially lethal and potentially mutagenic in both cell lines.

Animals↗