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Biomedical subjects

P Mack

Publications and source records attributed to P Mack.

67 records · Page 4Linked to original sources
PubMed1988

Combined intermittent dearterialization and intraperitoneal 5-fluorouracil administration for liver tumours in the rat.

Arterial occlusive therapy in the palliation of liver cancers has gone a long way since the first attempt at hepatic artery ligation. While efforts in permanent hepatic dearterialization have been frustrating in the face of fast developing collaterals, temporary inhibition of hepatic arterial blood flow appears to offer definite advantages. The effect of a single transient hepatic arterial occlusion with and without the addition of intraperitoneal 5FU was tested in Wistar-Furth rats bearing liver tumours. No advantage was observed in terms of tumour growth inhibition unless toxic doses of 5FU were used. A 5-day course of repeated treatment using intermittent dearterialization combined with intraperitoneal 5FU infusion was next tested and was found to be an efficient approach in reducing tumour growth rates. We prefer the intraperitoneal rather than the intraportal route for the infusion of oncolytic drugs because it avoids the problem of portal thrombosis and at the same time deals with any concomitant extrahepatic disease.

Animals↗
PubMed1988

Influence of 2-deoxy-D-glucose and arterial ischaemia on glucose oxidation and growth of liver cancer in the rat.

Malignant tissues are known to exhibit a high rate of glucose oxidation. It could therefore be hypothesized that reduction of glucose oxidation could be of benefit for the treatment of malignancies. We tested this approach, and by using [UL14C]glucose, we showed that glucose oxidation in a transplanted adenocarcinoma in the rat liver was 2.81 +/- 0.23 times as high as that of the surrounding liver tissue (P less than 0.01). In vivo treatment with intra-arterial 2-deoxy-D-glucose (2DG) infusion at 800 mg/kg via the gastroduodenal artery reduced the tumour/liver ratio of glucose oxidation to 1.88 +/- 0.12 (P less than 0.01). A similar inhibition of tumour glucose oxidation was obtained by 1 h of hepatic arterial ischaemia (P less than 0.05), or by ischaemia combined with 2DG infusion at 400 mg/kg (P less than 0.01). A 5-day course of intermittent hepatic dearterialization combined with continuous intra-arterial 2DG infusion at 400 mg/kg/day produced liver tumour growth retardation (P less than 0.01). We conclude that intermittent dearterialization reduces not only tumour growth but also the high tumour glucose oxidation. Dearterialization reduced glucose oxidation as much as 2DG did, which could be a mechanism behind reduced tumour growth.

Adenocarcinoma↗
PubMed1988

RNA labelling with 3H-orotic acid and 3H-fluorouracil of rat liver tumour following transient hepatic arterial ischaemia.

Recent studies have demonstrated that transient (1 h) hepatic arterial ischaemia is followed by increased incorporation of labelled thymidine into tumour DNA 24 h later. The present study aimed at investigating if and when there is a corresponding increase in incorporation of labelled 5-fluorouracil (5-FU) or orotic acid into tumour tissue. Incorporation was studied at 0, 6, 24 and 48 h after discontinuation of transient hepatic arterial ischaemia in Wistar-Furth rats having liver tumour. The transient ischaemia was followed by increased RNA and RNA/DNA ratios in normal liver but not in tumour. Incorporation of orotic acid into RNA and DNA was unchanged in tumour but increased at 0 and 6 h in normal liver. Incorporation of 5-FU decreased with time in liver and tumour DNA and in tumour RNA. It is suggested that 5-FU has an optimal effect on tumour tissue when infused immediately after transient hepatic arterial ischaemia.

Animals↗
PubMed1988

Pneumo-retroperitoneum associated with pneumatosis cystoides intestinals.

Pneumatosis cystoides intestinalis, a rare disease characterised by gas cysts involving portions of the intestinal tract, is obscure in its etiology and intriguing in its presentation. Amongst several theories a new concept suggest that retroperitoneal gas is a probable source of origin. Experimental studies in animals have demonstrated that air can track down the mediastinum into the retroperitoneum and thereby into the gut wall from an alveolar rupture. A case of pneumo-retroperitoneum in a patient with pneumatosis cystoides intestinalis is now reported.

Aged↗
PubMed1987

Role of receptors in metabolic interaction of histamine with human vascular endothelial cells and skin fibroblasts. An ordered sequence of enzyme action.

The interaction of histamine with an H1 receptor on human endothelial cells evokes production of the lipid mediator prostaglandin I2 (PGI2) and is accompanied by tachyphylaxis of this H1 receptor response (Baenziger, N. L., Fogerty, F. J., Mertz, L. F., and Chernuta, L. F. (1981) Cell 24, 915-923). We have explored the affected cells' capability for subsequent metabolic degradation of histamine molecules. Human vascular endothelial cells and skin fibroblasts exhibit a two-stage histamine degradation sequence whose participants are an enzyme native to the cells themselves and one provided from an extracellular source. Initially, the cells' endogenous histamine N-methyltransferase activity mediates conversion of cell-associated [3H]histamine to tele-methylhistamine with retention of this intermediate metabolite. Subsequently, in the presence of exogenous diamine oxidase derived from fetal calf serum or human placenta, cell-associated tele-methyl-histamine is further converted to the end product methylimidazoleacetic acid. After an initial lag phase lasting 3-6 min, the cell-associated radioactivity accumulates as methylimidazoleacetic acid at a linear rate substantially enhanced over that without diamine oxidase. The entire sequence is blocked by the histamine methyltransferase inhibitor homodimaprit. Accumulation of [3H]histamine metabolites by endothelial cells is saturable both with respect to exogenous diamine oxidase and to histamine. Thus this metabolic pathway is carried out at the level of the individual cell by means of binding sites or receptors for the substrate and for the distal degradative enzyme, diamine oxidase.

Amine Oxidase (Copper-Containing)↗
PubMed1987

Radiotherapy for pain relief in locally recurrent colorectal cancer.

Eighteen patients with local recurrence of colorectal cancer have been treated by external beam radiotherapy for pain relief. Seven received a fractionated course of 4500cGy and the remainder received single fractions of 1000cGy, a number being treated more than once. The median survival for all patients once recurrence had produced pain was 7 months. Treatment benefit was recorded in 71% treated by fractionated courses and in 66% by single fractions. The duration of pain relief was 3 months for each method. The repeatability of single fraction treatment indicates that this is a worthwhile alternative technique, particularly for those in poor general condition.

Colonic Neoplasms↗
PubMed1983

Regulation of cytotoxic reactivity to minor histocompatibility antigens by administration of Corynebacterium parvum.

B10.BR(H-2k) mice were primed with H-2-identical allogeneic CBA/J(H-2k) spleen cells and restimulated in vitro 14 days later to generate specific secondary cytotoxic lymphocytes. A single intravenous injection of primed mice with 700 micrograms of Corynebacterium parvum 7 days after alloimmunization markedly inhibited the subsequent secondary in vitro generation of cytotoxic cells. In addition, regulatory spleen cells were detected in alloimmunized C-parvum-injected mice that prevented the restimulation of primed control spleen cells. Suppressive activity could not be abrogated by treating regulatory cells with anti-theta antibody and complement or by removing phagocytic cells, but it was overcome by treatment with mitomycin C. Unfractionated regulatory cells suppressed responses in an antigen nonspecific fashion. However, cells remaining after carbonyl and iron treatment (nonphagocytic) could no longer suppress responses to third party alloantigens while maintaining significant suppression of anti-CBA responses. These data suggest the generation of two distinct suppressor cell types that can control the cytotoxic response to minor histocompatibility antigens: an antigen-nonspecific phagocytic cell and an antigen specific nonphagocytic, non-theta-bearing cell.

Adjuvants, Immunologic↗
PubMedDate not supplied

Apoptosis induced by hyperthermia in Dunn osteosarcoma cell line in vitro.

The effect of hyperthermia at 43.5 degrees C for 1 h on Dunn osteosarcoma cells was studied. With sham-heated cells (37 degrees C, 1 h) as the control, the hyperthermia treated cells were divided into five groups. Time 0 group was the cells that were harvested immediately after heated at 43.5 degrees C for 1 h. Whereas time 3, 6, 12, and 24 h groups were the cells that were collected respectively after reincubation at 37 degrees C for the above different time periods. The appearance of hyperthermia-induced apoptosis of Dunn osteosarcoma cells was demonstrated to be time dependent. With the confocal microscopic study and TUNEL staining, the morphological characteristics of apoptosis, condensed nuclei and fragmented nuclei were obvious when reincubated at 37 degrees C for 6 h after hyperthermic treatment. This hyperthermia-induced apoptosis was further confirmed by flow cytometric analysis on DNA contents. The sub-G1 region that was proposed as a marker of apoptotic cells was most significantly elevated at 6 h after hyperthermic treatment and, thereafter, decreased to the levels of control values by 24 h, as the apoptotic cells underwent secondary necrosis and degraded to debris. The DNA strand breaks, considered as the key biochemical event of apoptosis, were detected by the TUNEL assay. This study indicated that hyperthermia (43.5 degrees C for 1 h) can induce apoptotic changes on osteosarcoma cells in vitro very rapidly (within 6 h after treatment), and its occurrence might not be detected if the samples are not taken at several early time points after hyperthermia.

Apoptosis↗
PubMedDate not supplied

Outcome of ultrasonographic hip abnormalities in clinically stable hips.

A retrospective review was performed of 192 newborn hips in 112 patients referred for hip evaluation. The average age at presentation was 12.7 days, with average radiographic follow-up of 15.9 months. Inclusion criteria for our study were a normal physical examination of the hip without evidence of instability and an ultrasound examination that was considered abnormal. Pavlik harness treatment was chosen at the discretion of the treating physician. At final follow-up, dysplasia was defined as greater than two standard deviations above the mean acetabular index (AI) for age. Group I consisted of 43 hips that had Pavlik treatment, and group II consisted of 149 hips that did not receive treatment. There was no difference in these two groups with respect to risk factors for dysplasia or the initial abnormalities seen on ultrasound evaluation, although patients in group I had less coverage of the femoral head during stress maneuvers. No hip in group I and two (1.3%) hips in group II were considered dysplastic (AI > 2 SD) at final radiographic follow-up (p > 0.10). There was no correlation between the severity of the ultrasound abnormality at birth and the subsequent presence of dysplasia (p > 0.10). The two hips considered dysplastic on radiograph were not being actively treated. When the hip examination of a newborn hip younger than 1 month is normal, a screening ultrasound does not appear to predict accurately subsequent hip dysplasia. In this specific setting, an initial screening ultrasound may be too sensitive and does not appear warranted.

Analysis of Variance↗
PubMedDate not supplied

Quercetin-induced apoptosis in the monoblastoid cell line U937 in vitro and the regulation of heat shock proteins expression.

Quercetin, a widely distributed plant flavonoid, inhibits the growth of tumor cells and the expression of heat shock proteins. In this study, we examined quercetin-induced apoptosis of U937 cells in vitro and the regulation of heat shock proteins expression. The quercetin-induced apoptosis was demonstrated to be dose- and time-dependent. Flow cytometry analysis revealed that sub-G1 peak appeared at 12 hours, 24 hours and 48 hours respectively when treated with 50 mM of quercetin and at 6 hours, 12 hours, 24 hours and 48 hours with 100 mM of quercetin. Agarose gel electrophoresis demonstrated a typical ladder-like pattern of DNA fragments in the same time intervals with 50 mM of quercetin and at 6 hours only with 100 mM of quercetin. The distribution of DNA contents showed that U937 cells were accumulated mainly at G2/M phase when incubated with 50 mM of quercetin for 24 hours and 48 hours. There was no specific effect on cell cycle distribution at 100 mM of quercetin. On exposure to 100 mM of quercetin, the inhibition of hsp27 and hsp70 expression was observed from 12 hours to 48 hours and 6 hours to 48 hours respectively. The inhibition of hsp90 expression was not found eiyher at 50 mM or 100 mM of quercetin exposure. When incubated with 50 mM of quercetin, there was no inhibitory effect on hsp27, hsp70 and hsp90 expression by the Western blot analysis. These results suggested that it is dependent on the dose and exposure time of quercetin to induce apoptosis of U937 cells in vitro, to affect the cell cycle distribution and to regulate the expression of hsp27 and hsp70.

Apoptosis↗
PubMedDate not supplied

Nitrobenzylthioinosine-binding protein overexpression in human breast, liver, stomach and colorectal tumour tissues.

Using high-affinity [3H]nitrobenzylthioinosine (NBMPR) equilibrium binding assays, fresh human tumour tissues were consistently found to be over expressing NBMPR binding proteins at levels 1.5 to 5-fold higher than in corresponding normal tissues. The mean Bmax values for breast (n = 6), liver (n = 2) and stomach (n = 4) tumour tissues were 2.89 +/- 0.76, 0.5I +/- 0.03 and 1.38 +/- 0.43 fmol/micrograms of plasma membrane protein, respectively. These values were all significantly higher (p < 0.05, student paired t-test) than those for the normal tissues (Bmax's = 0.97 +/- 0.05, 0.20 +/- 0.02 and 0.51 +/- 0.05 fmol/microgram of protein for breast, liver and stomach, respectively). For colorectal tissues (n = 10), the mean Bmax value for the tumour specimens (1.36 +/- 0.24 fmol/microgram of protein) was also significantly higher (p < 0.005, student paired t-test) than those for the normal specimens taken 5 cm (0.42 +/- 0.03 fmol/microgram of protein) and 10 cm (0.47 +/- 0.04 fmol/(g of protein) away from tumour site. There were no consistent and significant differences in the binding affinities between tumour and normal tissues in these four tissue types (Kd values ranged from 0.07 to 1.0 nM, p > 0.05, student paired t-test).

Adenocarcinoma↗