Thorotrast-Induced Multiple Primary Malignant Tumors of the Liver--Cholangiocarcinoma and Malignant Hemangioendothelioma

A case of multiple primary malignant tumors of the liver (cholangiocarci-nomaand malignant hemangioendothelioma) that developed 40 yearsafter Thorotrast administration is described, with radiologicaland autoradiographic findings. The estimated organ dose to theliver was approximately 580 rads.     

EFFECTS OF ALTHESIN ON CEREBRAL BLOOD FLOW AND OXYGEN CONSUMPTION IN MAN

Cerebral circulation and metabolism during Althesin anaesthesiawere studied in seven healthy patients. Althesin was given ina single dose of 0.1 ml/kg and thereafter infused at a constantrate of 0.3 ml/kg/h. During Althesin infusion, the cerebralblood flow (CBF), the cerebral metabolic rate for oxygen (CMRo₂)were 29 ±10 ml/100 g/min and 1.7 ± 0.4 ml/100g/min, respectively. These values were significantly differentfrom those obtained in awake subjects in our laboratory (CBF:46±7 ml/100 g/min; CMRo₂: 3.1 ±0.6 ml/100 g/min).During CBF measurement, the mean cerebral perfusion pressure,cerebral vascular resistance (CVR) and arterial carbon dioxidetension (Pa_CO2) were 89±16mmHg,3.4±1.3 mm Hg/ml/100g/min, and 36±9mmHg, respectively. The relationship betweenCBF and .Pa_CO2 was studied and it was found that during Althesinanaesthesia reactivity of cerebral vessels to the alterationof Pa_CO2 was maintained. It is concluded that Althesin causedcerebral metabolic depression which was accompanied by a decreasein CBF and an increase in CVR.     

Hepatocyte growth factor: Molecular structure and implications for a central role in liver regeneration

Hepatocyte growth factor (HGF) is a most potent factor for mature parenchymal hepatocytes in primary culture and may act as a trigger for liver regeneration. We purified HGF from rat platelets to homogeneity and cloned both human and rat HGF cDNA. HGF is a heterodimer molecule composed of the 69 kDa alpha-subunit and the 34 kDa beta-subunit. HGF has no amino acid sequence homology with other known peptide growth factors and possesses the highest potential among known growth factors to stimulate proliferation of hepatocytes in primary culture. HGF is derived from a single chain precursor of 728 amino acid residues and the precursor is proteolytically processed to form a two-chain mature HGF. The alpha-subunit of HGF contains 4 kringle structures and HGF has a homology (38%) with plasmin. Biologically active recombinant human HGF could be expressed from COS-1 cells and CHO cells transfected with cloned cDNA. HGF activity and the HGF mRNA level are markedly increased in the liver following insult such as hepatitis, by the administration of hepatotoxins, ischaemia, physical damage and partial hepatectomy. Moreover, HGF mRNA is induced in the lung and kidney, in the presence of liver injury. In situ hybridization revealed that HGF-producing cells in liver are non-parenchymal liver cells, presumably Kupffer and sinusoidal endothelial cells. Therefore, HGF from neighbouring cells (Kupffer and sinsuoidal endothelial cells) and distal organs (lung and kidney) may function as a trigger for liver regeneration by both a paracrine mechanism and an endocrine mechanism. HGF has mitogenic activity for renal tubular epithelial cells, epidermal melanocytes and keratinocytes as well as mature hepatocytes, and has the potential to promote cell migration for some epithelial cells, including normal human keratinocytes. Since cell growth and cell motility are relevant to tissue repair and embryogenesis, HGF may well have important roles in tissue repair and embryogenesis as well as in liver regeneration.     

Decreased serum carnitine is independently correlated with increased tissue accumulation levels of advanced glycation end products in haemodialysis patients

Aim: There is accumulating evidence that advanced glycation end products (AGE) play a role in cardiovascular disease (CVD) in patients with haemodialysis (HD). Carnitine deficiency is frequently observed in HD patients, which may also contribute to CVD. In this study, we examined whether carnitine deficiency was independently associated with increased tissue accumulation levels of AGE in HD patients. Methods: One hundred and twenty‐nine HD patients underwent determinations of blood chemistries including serum level of carnitine. Tissue AGE levels were evaluated by measuring skin autofluorescence with an AGE‐reader. Results: Serum carnitine levels were significantly lower, while skin AGE levels were significantly higher in HD patients compared with healthy controls (P < 0.001). In univariate analysis, β₂‐microglobulin (β₂‐MG) and carnitine (inversely) were correlated with skin AGE levels. Multiple stepwise regression analysis revealed that carnitine levels were one of the independent determinants of skin AGE levels (P = 0.024). When β₂‐MG‐adjusted skin AGE levels were stratified by serum carnitine levels, a statistical significance and dose‐response relationship were observed (P = 0.043). Furthermore, skin AGE levels were one of the independent determinants of serum carnitine levels as well (P = 0.012). Conclusion: The present study demonstrated that decreased carnitine levels were independently associated with increased skin AGE levels in HD patients. Since carnitine is reported to inhibit the formation of AGE in vitro, our study suggests that supplementation of carnitine may be a therapeutic target for preventing the accumulation of tissue AGE and subsequently reducing the risk of CVD in HD patients.