Yuya Ueyama

Hypocholesterolaemic factor from gallbladder cancer cells

A patient is reported with drug-resistant familial hypercholesterolaemia in whom serum cholesterol fell after the onset of gallbladder cancer with intraperitoneal invasion. Cancer cells were obtained from ascitic fluid and a cultured cell line established. Incubation of the culture medium of these cells with skin fibroblasts from the patient and from normal subjects increased low-density lipoprotein (LDL) receptor activity in a dose-dependent manner. These results show that gallbladder cancer cells from this patient secrete a substance that stimulates LDL receptor activity. This substance may have contributed towards reduction of serum cholesterol.

Extramedullary plasmacytoma (EMP) of urinary bladder.

An extramedullary plasmacytoma (EMP) is presented with an isolated lesion in the urinary bladder accompanying an IgG-K paraproteinemia. After a short-term oral melphalan administration, the tumor soon regressed together with the paraprotein, and has never recurred during the two-year follow-up. This is the fourth case of primary EMP of the urinary bladder reported in the literature.

Familial hypercholesterolaemia-like syndrome with apolipoprotein E-7 associated with marked Achilles tendon xanthomas and coronary artery disease: a report of two cases.

Abstract. We observed two patients with hypercholesterolaemia and tendon xanthomas associated with apolipoprotein (apoE‐7) E‐7, a rare variant of the apoE isoforms. Both suffered from coronary artery disease and had undergone a coronary bypass operation. Their cholesterol levels were 268 and 310 mg dl‐1, respectively. Both patients had marked xanthomas in the Achilles tendons. Both also suffered from diabetes. Although their clinical and laboratory findings were compatible with typical familial hypercholesterolaemia (FH), the analysis of low‐density lipoprotein (LDL) receptors in cultured fibroblasts showed no abnormality of binding, internalization or degradation of 125I‐LDL.

Non-macrophage-related accumulation of cholesterol during probucol treatment in familial hypercholesterolemia: report of two cases

Two patients receiving long-term (3-4 years) treatment with probucol for familial hypercholesterolemia (FH) developed diffuse yellow lesions over the upper eyelids suggesting lipid storage in those tissues (diffuse lipid-storage lesions). Interestingly, each patient had shown a substantial reduction in their cholesterol levels together with a marked regression of their tendon xanthomas or typical xanthelasmas during treatment. To evaluate the role of probucol in this unusual finding we conducted histological and immunochemical evaluations of the lesions (removed surgically) and compared them with those of a non-probucol-treated subject with FH and typical audinal xanthelasma. In both probucol-treated patients the lesions were filled with foam cells and contained large amounts of cholesteryl ester. However, immunochemical analysis of the lesions of one patient using anti-monocyte monoclonal antibody (HAM56) demonstrated that they were not composed of macrophage-derived foam cells in contrast to those of the non-probucol-treated subject which stained clearly with anti-monocyte monoclonal antibody. In each case the foam cells did not react with muscle-actin-specific monoclonal antibody (HHF35). It appears that non-macrophage-related diffuse lipid-storage lesions may occur even during treatment with probucol despite the reduction in cholesterol levels and the regression of xanthomas, suggesting that probucol may alter the distribution of cholesterol from the macrophage to other cells.

A compound heterozygote for familial hypercholesterolaemia with a homozygous mother

Homozygous familial hypercholesterolaemia (FH) is a rare disorder in which the patients develop severe hypercholesterolaemia and premature coronary atherosclerosis from childhood. Here we report a unique family with clustering of homozygous FH. The proband was a 25‐year‐old man, who showed marked hypercholesterolaemia, multiple xanthomas and severe coronary atherosclerosis. His mother also showed the typical characteristics of homozygous FH. Sequencing analysis of the low‐density lipoprotein receptor gene revealed that he was a compound heterozygote, carrying two different point mutations. One was a novel mutation, FH Wakayama (Cys→A Ser at 317), derived from his mother, and the other was a recurrent mutation, FH Niigata (T→A C at 1845+2, 5′ splice signal in intron 12), derived from his father. The proband we report seems to be a very rare case of an FH homozygote born from a homozygous mother.