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Biomedical subjects

P Mack

Publications and source records attributed to P Mack.

At least 55 records · Page 3Linked to original sources

Studies of epidermal growth factor (EGF) receptor in plasma membrane from rat liver and hepatoma tissues.

Plasma membrane purified from Buffalo rat liver tissue not only had the ability to bind 125I-EGF (2.77 pg of EGF/mg of membrane protein), but also exhibited both high (Kd = 0.08 nM) and low (Kd = 5.67 nM) affinity receptors. However, the binding of EGF to hepatoma plasma membrane was insignificant. EGF receptor in plasma membrane from normal liver tissue was identified by ECL Western blotting using monoclonal anti-EGF receptor antibody and phosphorylated via the stimulation of EGF. This phosphorylation was inhibited by genistein, a tyrosine kinase inhibitor. However, these effects were not observed in hepatoma cell membrane. These results suggest that plasma membrane purified from normal rat liver tissue has a high level of functional EGF receptor, whereas, hepatoma plasma membrane lacks the receptor.

Animals↗

Anticonvulsant activities of some arylsemicarbazones displaying potent oral activity in the maximal electroshock screen in rats accompanied by high protection indices.

Various semicarbazones derived from aryl aldehydes, phenylalkyl aldehydes, and phenylalkyl ketones as well as some related compounds were evaluated for anticonvulsant activity. Most of the compounds displayed anticonvulsant activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens accompanied by neurotoxicity when given to mice by the intraperitoneal route. However quantitative data revealed protection indices (TD50/ED50) of less than 4 in general. Oral administration of the compounds to rats led to excellent potency in the MES screen accompanied by high protection indices while virtually no activity in the scPTZ test was displayed. These observations support the theory that one large hydrophobic group (in this case the aryl ring) and two electron donor atoms (present in the semicarbazono group) are requirements for protection in the MES screen. In general, the semicarbazones had rapid onsets of action, and one of the ways in which these compounds displayed their anticonvulsant activity is likely to be interaction with chloride channels. Empirical and semiempirical conformational calculations indicated that certain molecular fragments and hydrophobicity of these molecules affect bioactivity.

Administration, Oral↗

Experience with liver resection after hepatic arterial chemoembolization for hepatocellular carcinoma.

The use of percutaneous transcatheter hepatic arterial chemotherapy and embolization in the treatment of primary liver cancer has become increasingly popular in recent years. The authors employed this method, using a combination of cisplatin, mitomycin C, 5-fluorouracil, and ethiodized oil (Lipiodol) or absorbable gelatin sponge in 30 patients with huge liver cancers (diameter range, 5.6-12.0 cm) as a preliminary treatment before liver resection. Significant tumor regression occurred after this treatment, converting these tumors into resectable lesions that were excised successfully later. Before surgery, chemoembolization was done once every 4-6 weeks. The patients underwent 1-5 treatment sessions (mean, 2.9) and then waited 1-4 months (mean, 2.4 months) before undergoing surgery. Alpha-fetoprotein levels decreased to normal in seven patients. The tumor diameters were reduced by 31.6 +/- 15.2% (2.3 +/- 1.2 cm) and the percent tumor necrotic area ranged from 40-100%. Adhesions of the tumor to the diaphragm and thickening of the hepatoduodenal ligament and gallbladder wall were the primary operative findings, but they did not significantly complicate the surgery. There was one postoperative death from acute pulmonary embolism. The 1-year, 2-year, and 3-year survival rates were 88.89%, 77.03%, and 77.03%, respectively. Although these patients still are being followed to assess their long-term survival, this treatment appears promising for patients with advanced huge liver cancers who hitherto have been denied surgery on grounds of unresectability.

Adult↗

Resection of segment VIII of liver for treatment of primary liver cancer.

The close relationship of hepatic segment VIII to the right and middle hepatic veins and to the inferior vena cava makes liver cancer resection in this region extremely difficult. Resection of segment VIII was performed in 25 patients with primary liver cancer between January 1970 and May 1990. Most resections were performed with just porta hepatis occlusion, but some cases required the technique of total hepatic vascular exclusion, otherwise known as "bloodless hepatic resection." It involved control of both the suprahepatic and infrahepatic inferior vena cavae in addition to control of the porta hepatis. Major modifications to the original technique were made, and the 1-, 3-, and 5-year survival rates were 90.5%, 50.0%, and 37.5%, respectively. Two patients have survived 12 and 15 years, respectively. Both of them are alive to date and have returned to work.

Adult↗

krox 20 messenger RNA and protein expression in the adult central nervous system.

krox 20 is an inducible immediate early response gene. To determine if krox 20 has a physiological role in the adult central nervous system (CNS), this study sought to demonstrate the presence of krox 20 in adult rat brain. RNA analysis showed the presence of krox 20 transcripts in the CNS, including the cortex. Polyclonal antibodies to a Krox 20 fusion protein demonstrated 79 and 55 kDa antigens in nuclear CNS homogenates. Neither RNA nor protein analysis was able to demonstrate an induction of krox 20 by a seizure at times when other immediate early response genes are known to be induced. Immunohistochemical analysis revealed staining at several levels throughout the nervous system. This staining was predominantly nuclear, consistent with the role of krox 20 as a transcription factor. These data show that krox 20 is present in the adult CNS, yet differs in response to stimuli as compared to other related transcription factors with a zinc finger motif, such as NGFI-A and NGFI-C.

Animals↗

Are fathers' views important?

A survey by health visitors of the behaviour of children between the ages of three and eight revealed that mothers consistently rate children's behaviour as significantly more problematic and more intense than fathers do. Both mothers and fathers viewed the behaviour of boys as more difficult than girls. Pamela Mack, Karen Trew discuss the value of using a behaviour checklist as one aide in the assessment of childhood behaviour problems, with particular emphasis on the importance of involving fathers.

Child↗

The histamine degradative uptake pathway in human vascular endothelial cells and skin fibroblasts is dependent on extracellular Na+ and Cl-.

We have previously reported that human vascular endothelial cells and skin fibroblasts carry out degradation of [3H]histamine by a mechanism involving two successive enzymatic steps: imidazole ring tele-methylation by the cells' endogenous methyltransferase and subsequent amine oxidation by an exogenous diamine oxidase. Both histamine and the exogenous second enzyme in the pathway associate with the cells via separate binding sites or receptors. The enzymatic degradation process results in cellular accumulation of the proximal and distal metabolites tele-methylhistamine and 1-methyl-4-imidazoleacetic acid (MIAA) (Haddock, R. C., Mack, P., Fogerty, F. J., and Baenziger, N. L. (1987) J. Biol. Chem. 262, 10220-10228). We have now demonstrated that this two-stage histamine degradative pathway is dependent on Na+ and Cl- in the extracellular environment. Accumulation of [3H] histamine-derived products is partially inhibited under conditions of Na+ deprivation and more substantially when Cl- is also withdrawn. The individual tele-methylation and amine oxidation enzymatic reactions themselves are unaffected or actually facilitated under these conditions. This indicates that it is the cellular mechanism for uptake coupled to the degradative pathway which reflects the cation and anion dependency. Restoration of degradative uptake displays a biphasic Na+ concentration curve, suggesting that the uptake process may be driven by multiple components. These findings indicate a role for both inward Na+ and Cl- ion movement in this cellular degradative uptake mechanism.

Biological Transport↗

System of denture assessment.

Denture complaints and problems can be complex in origin, time consuming to analyse, and sometimes expensive to rectify. A phased or sequential system of assessment can provide a framework on which to base the many clinical tests that may be required for the successful diagnosis of a denture problem, and will help ensure that no important factor is accidentally missed. A short mnemonic is presented which covers the assessment of the patient, the denture base and the teeth of the prosthesis. A variation of the mnemonic has been is use for several years. It is hoped that its publication might prove of value to those who, from time to time, are presented with a patient who has a denture problem.

Dental Occlusion↗

Insulin response to glucose challenge after transient hepatic dearterialization for rat liver malignancy.

In the palliative treatment of liver malignancy, hepatic dearterialization is being increasingly used. To study the metabolic consequences of this treatment, the present investigation was conducted to elucidate the insulin, glucose, and lactate responses to an intravenous glucose challenge after transient hepatic dearterialization in a liver tumor model in inbred Wistar-Furth rats. We found that nonfasted rats bearing dearterialized liver tumors showed slightly higher basal plasma glucose levels and an exaggerated elevation of plasma glucose during the glucose infusion compared to the controls. Further, they had a depressed insulin response to the glucose challenge. Their glycogen stores were at the same time depleted, in both the liver and the tumor tissues, and the plasma lactate production during the glucose infusion was elevated after dearterialization. We conclude that immediately after hepatic dearterialization in rats with liver malignancies, glucose intolerance and impaired glucose-induced insulin secretion exist.

Adenocarcinoma↗

Glucose turnover in rats undergoing transient dearterialization for liver malignancy.

With the development of new techniques for hepatic dearterialization, their use in the treatment of liver malignancies has increased. It is therefore important to study the metabolic consequences of hepatic dearterialization. The present investigation determined the glucose turnover during hepatic dearterialization in the rat with the use of a primed tracer [( 3-3H]glucose) infusion technique. It was found that the glucose elimination rate was diminished during dearterialization in both tumor-free and tumor-bearing rats in the fasting state. Hepatic glucose production was maintained in tumor-free rats leading to hyperglycemia, but hepatic glucose production decreased in tumor-bearing rats resulting in hypoglycemia. Pretreatment of tumor-bearing rats overnight with an intravenous glucose infusion did not counteract the reduced hepatic glucose production during dearterialization in tumor-bearing rats. The hypoglycemic tendency therefore remained. This could be caused by the exaggerated glucose consumption that is known to occur in tumor tissues. It is concluded that hepatic dearterialization reduces glucose elimination in rats, and, in tumor-bearing rats, the procedure also reduces hepatic glucose production.

Animals↗

Retarding liver cancer growth in the rat by transient repeated hepatic dearterialization.

The effect of repeated ischemic episodes to experimental liver tumors is studied in a group of inbred Wistar-Furth rats. A vascular occluder model was developed specially for the purpose of delivering intermittent compressions to the hepatic artery in the rat. With five daily 1-hr occlusions of the hepatic artery, rats benefited from significantly reduced tumor growth rates compared with controls that underwent sham operation (P less than 0.05). In contrast to results from previous pig experiments, it is demonstrated by angiographic studies that repeated transient dearterialization does not entirely overcome the problem of collateral vessel formation in the rat. Tumor neovascularization continues irrespective of whether the tumor is being dearterialized. It is also observed that in both normal and tumor rats, collateral channels from the left gastric artery temporarily open up when the hepatic artery is obstructed but disappear on reestablishment of flow. As such types of collateral flow are beyond our control, it is imperative that future developments in vascular occlusion therapy should aim at shortening ischemia time and combining with chemotherapy.

Adenocarcinoma↗

Acute ischemic liver failure in the rat: a reproducible model not requiring portal decompression.

We report a model of acute ischemic liver failure which does not require temporary or permanent portal decompression. The model is induced by segmental ischemia of the median and left lateral lobes for 100 min by a vascular clamp applied on the afferent vessels. Declamping is followed by resection of the nonischemic right lateral and caudate lobes. No portal stasis occurs as blood flow to the right lateral and caudate lobes is maintained during the period of clamping. The 24-hour mortality is 76.5%. Evidence of severe liver damage is shown by histological and biochemical studies.

Acute Disease↗

Acute omental infarction--a report of six cases.

Six cases of acute omental infarction, a rare entity, are reported. Four of them are secondary to torsion and two are cases of primary infarction. Appendicitis is the most common mode of presentation of this condition. Except for one patient who was obese, no predisposing factors were discernible in these patients. The aetiology and pathogenetic mechanisms of this disease were reviewed.

Acute Disease↗

Cholecysto-duodeno-colic fistula--a case report.

A rare case of cholecysto-duodenal-colic fistula presenting with non-faeculent vomiting, diarrhoea and loss of weight and appetite is reported. This fistula was demonstrated both by barium and endoscopic studies. She was treated with a simple closure of the fistulous tract and a cholecystectomy with good results. The surgical management of this condition is simple and rewarding.

Aged↗

Multiple splenic abscesses following Pseudomonas sepsis.

Splenic abscess is an unusual clinical entity, which in most cases is secondary to metastatic spread of bacteria from a primary site of infection. Before the antibiotic era, Salmonella typhi was a common offending organism but now staphylococci and streptococci are predominant organisms. We report two rare cases of multiple splenic abscesses caused by Pseudomonas infection. One case followed Pseudomonas septicaemia and the other was secondary to Pseudomonas pseudomallei osteomyletis of the femur. Both cases underwent splenectomy and promptly recovered.

Abscess↗