Biomedical subjects

Y Wu

Publications and source records attributed to Y Wu.

At least 397 records · Page 22Linked to original sources

PubMed2000

The PHSRN sequence induces extracellular matrix invasion and accelerates wound healing in obese diabetic mice.

The PHSRN sequence of the plasma fibronectin (pFn) cell-binding domain induces human keratinocytes and fibroblasts to invade the naturally serum-free extracellular matrices of sea urchin embryos. The potency of acetylated, amidated PHSRN (Ac-PHSRN-NH(2)) is significantly increased, making it more active on a molar basis than the 120-kDa cell-binding domain of pFn. Arginine is important to this activity because PHSAN and PHSEN are inactive, as is a randomized sequence peptide, Ac-HSPNR-NH(2). One treatment with Ac-PHSRN-NH(2) stimulates reepithelialization and contraction of dermal wounds in healing-impaired, obese diabetic C57BL6/KsJ db/db mice. Wound closure is equally rapid in treated db/db and db/+ mice and may be more rapid than in untreated nondiabetic db/+ littermates. In contrast, treatment with either Ac-HSPNR-NH(2) or normal saline (NS) has no effect. Analysis of sectioned db/db wounds shows that, in contrast to treatment with Ac-HSPNR-NH(2) or NS, a single Ac-PHSRN-NH(2) treatment stimulates keratinocyte and fibroblast migration into wounds, enhances fibroplasia and vascularization in the provisional matrix, and stimulates the formation of prominent fibers that may be associated with wound contraction.

Animals↗

PubMed2000

Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration.

Emerging data suggest that VEGF receptors are expressed by endothelial cells as well as hematopoietic stem cells. Therefore, we hypothesized that functional VEGF receptors may also be expressed in malignant counterparts of hematopoietic stem cells such as leukemias. We demonstrate that certain leukemias not only produce VEGF but also express functional VEGFR-2 in vivo and in vitro, resulting in the generation of an autocrine loop that may support leukemic cell survival and proliferation. Approximately 50% of freshly isolated leukemias expressed mRNA and protein for VEGFR-2. VEGF(165) induced phosphorylation of VEGFR-2 and increased proliferation of leukemic cells, demonstrating these receptors were functional. VEGF(165) also induced the expression of MMP-9 by leukemic cells and promoted their migration through reconstituted basement membrane. The neutralizing mAb IMC-1C11, specific to human VEGFR-2, inhibited leukemic cell survival in vitro and blocked VEGF(165)-mediated proliferation of leukemic cells and VEGF-induced leukemic cell migration. Xenotransplantation of primary leukemias and leukemic cell lines into immunocompromised nonobese diabetic mice resulted in significant elevation of human, but not murine, VEGF in plasma and death of inoculated mice within 3 weeks. Injection of IMC-1C11 inhibited proliferation of xenotransplanted human leukemias and significantly increased the survival of inoculated mice. Interruption of signaling by VEGFRs, particularly VEGFR-2, may provide a novel strategy for inhibiting leukemic cell proliferation.

Animals↗

PubMed2000

Angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism in hypertensive patients with different degrees of obstructive sleep apnea.

To investigate the role of the angiotensin-converting enzyme gene (ACE) insertion (I)/deletion (D) polymorphism in hypertensive patients with different degrees of obstructive sleep apnea (OSA). A case-control study was performed. One hundred seventy four Chinese subjects were divided into four groups depending on the severity of OSA as follows: 1) normal control group (NC, n=68), 2) isolated hypertension group (HT, n=45), 3) hypertensive patients with mild OSA group (MO, n=27), and 4) hypertensive patients with moderate to severe OSA group (MSO, n=34). The distribution of ACE gene I/D allele and genotypes were analyzed in the subject population, as was an OSA pedigree. The study showed that the frequency of ACE gene I/D polymorphism differed significantly among the four groups. The frequency of I allele and II genotype were significantly higher in the MSO group than in the other groups (p<0.05). The distribution of I allele and II genotype showed no significant difference between any of the other groups (p>0.05, respectively). Meanwhile the higher frequency of I allele and II genotype was observed in the OSA pedigree. The higher frequency of ACE gene I allele and II genotype were closely associated with the hypertensive patients with MSO. The inherited factors played an important role in the pathogenesis of hypertensive patients with MSO.

Adult↗

PubMed2000

Biological activity of CD-ring modified 1alpha,25-dihydroxyvitamin D analogues: C-ring and five-membered D-ring analogues.

Nonsteroidal analogues of 1alpha,25(OH)2D3, lacking either the full five-membered D ring (C-ring analogues) or the full six-membered C ring (D-ring analogues) are more potent inhibitors of cell proliferation or inducers of cell differentiation than is 1alpha,25(OH)2D3. Maximal superagonistic activity was seen for the C-ring analogue with a 24(R)-hydroxyl group in the side chain [30- to 60-fold the activity of 1alpha,25(OH)2D3]. The 19-nor-16-ene-26,27-bishomo C-ring analogue showed the best ratio of antiproliferative to calcemic effects (1275-fold better than 1alpha,25(OH)2D3 and severalfold better than all vitamin D analogues so far described). The analogues are able to stimulate specific vitamin D-dependent genes and are active in transfection assays using an osteocalcin promoter VDRE. Low binding affinity to the vitamin D binding protein, differences in metabolism, or affinity for the vitamin D receptor (VDR) are not the most important explanations for the enhanced intrinsic activity. However, the analogues are able to induce conformational changes in the VDR, which makes the VDR-ligand complex more resistant against protease digestion than is 1alpha,25(OH)2D3. In contrast to 20-epimer steroidal vitamin D analogues, 20-epimer C-ring analogues were less potent than analogues with a natural C-20 configuration. In conclusion, several nonsteroidal vitamin D analogues are superagonists of 1alpha,25(OH)2D3 despite lower receptor affinity and, for the C-ring analogues, higher flexibility of the side chain; moreover, they have a better selectivity profile than all analogues yet published.

Calcitriol↗

PubMed2000

Parathyroid hormone regulates transforming growth factor beta1 and beta2 synthesis in osteoblasts via divergent signaling pathways.

Parathyroid hormone 1-34 [PTH(1-34)] was shown to increase transforming growth factor beta1 (TGF-beta1) and TGF-beta2 concentrations in supernatants of cultured human osteoblasts and to increase TGF-beta1 and TGF-beta2 messenger RNA (mRNA) concentrations and gene transcription in these cells. Because PTH(1-34) activates both protein kinase C (PKC) and protein kinase A (PKA) pathways in osteoblasts, we investigated the role of each kinase pathway in activation of TGF-beta isoforms. PTH(29-32), which activates the PKC pathway in rat osteoblasts, increased TGF-beta1 but not TGF-beta2 concentrations in supernatants of osteoblasts. Phorbol myristate acetate (PMA), a PKC agonist, increased TGF-beta1 but not TGF-beta2 concentrations. Specific PKC antagonists safingol and Gö6976 attenuated PTH(1-34)-mediated increases in TGF-beta1 but not TGF-beta2 synthesis. PTH(1-31), which increases PKA activity in several cell culture systems, increased TGF-beta2 but not TGF-beta1 concentrations in human osteoblast supernatants. Forskolin, a PKA agonist, increased TGF-beta2 but not TGF-beta1 concentrations in supernatants of human osteoblasts. The PKA antagonist H-89 blunted PTH(1-34)-mediated increases in TGF-beta2 but not TGF-beta1 synthesis. Our results are consistent with the concept that PTH increases TGF-beta1 expression and secretion by pathways that involve the PKC pathway, whereas it increases TGF-beta2 expression and secretion via the PKA pathway.

Animals↗

PubMed2000

Structure, composition, and maturation of newly deposited calcium-phosphate crystals in chicken osteoblast cell cultures.

Characterization of the very early calcium phosphate (CaP) crystals deposited in bone or in osteoblast cell cultures has been hampered by the overwhelming presence of organic matrix components and cells that obscure spectral analyses. We have overcome this problem using isolated protein-free crystals and have obtained new data including 31P nuclear magnetic resonance (NMR) spectra for the first time from mineral crystals deposited during osteoblast calcification in culture. Crystals were isolated from cultures at two time points: (a) at first calcium accumulation (day 8-10) and (b) after 60 days of culture, to assess maturational changes. The analyses show that the chemical composition overall and short range order of the early and mature crystals are characteristic of the apatite crystals found in young embryonic chick bone in vivo. No mineral phase other than apatite was detected by any of the methods used. 31P NMR spectroscopy identified the HPO4 groups as those present in bone apatite. Similar to bone apatites, no OH groups were detected by Fourier transform infrared (FTIR) spectroscopy. The temporal maturational changes in composition and structure of the mineral phase were difficult to assess because of the continuous deposition of crystals throughout culturing. The pathway of the maturational changes observed were similar to those occurring in chick bone in vivo and synthetic apatite crystals in vitro although to a much smaller extent.

Animals↗

PubMed2000

Low prevalence of a periodontitis-associated interleukin-1 composite genotype in individuals of Chinese heritage.

BACKGROUND: Polymorphisms in the interleukin-1 (IL-1) gene cluster have been associated with an increased risk of developing certain diseases. A specific composite genotype of IL-1A and IL-1B polymorphisms, consisting of allele 2 of both IL-1A +4845 and IL-1B +3954 (formerly +3953) has been associated with an increased risk of severe adult periodontitis. Approximately 30% of the European population carry this genotype. The prevalence of the above IL-1A and IL-1B composite genotype in populations of different ethnic origins is unknown. Therefore, the primary aim of this study was to determine the prevalence of the IL-1 composite genotype in individuals of Chinese heritage, since epidemiologic studies indicate that periodontitis is widespread among ethnic Chinese. An additional aim was to evaluate if there was an association between the composite genotype and the severity of periodontal disease. METHODS: A convenience sample of 300 volunteers of Chinese heritage (ages 21 to 69 years) received a periodontal examination including full-mouth clinical attachment loss measurements, probing depths, plaque index scores, and bleeding on probing. Blood was collected from a fingerstick and placed on a blotting paper card. The blood samples were analyzed for IL-1A +4845 and IL-1B +3954 polymorphisms using polymerase chain reaction (PCR)-based methods. RESULTS: Only 7 of the 300 subjects (2.3%) carried the composite IL- 1 genotype consisting of allele 2 of both IL-1A +4845 and IL-1B +3954. Allele 2 of the IL-1A +4845 polymorphism was carried by 17.0% (51/300) of the subjects; of these, only 2 were homozygous. Allele 2 of the IL-1B +3954 polymorphism was much rarer with only 3.3% (10/300) of the study population carrying this marker. All of the people who carried the IL-1B polymorphism were heterozygous. Too few of the subjects were positive for the IL-1 composite genotype to establish any relationship with the susceptibility to periodontitis. CONCLUSIONS: It was concluded that the prevalences of both IL-1A and IL-1B polymorphisms are dramatically lower in Chinese than those reported for Europeans. Findings from this study bring into question the usefulness of the composite genotype of allele 2 of both IL-1A +4845 and IL-1B +3954 as a method for determining the susceptibility of Chinese patients to adult periodontitis.

Adult↗

PubMed2000

Mice with gene disruption of both endothelial and neuronal nitric oxide synthase exhibit insulin resistance.

Studies from our laboratory using acute pharmacologic blockade of nitric oxide synthase (NOS) activity have suggested that nitric oxide (NO) has an important role in regulating carbohydrate metabolism. We now report on insulin sensitivity in mice with targeted disruptions in endothelial NOS (eNOS) and neuronal NOS (nNOS) genes compared with their wild-type (WT) counterparts. Mice underwent hyperinsulinemic-euglycemic clamp studies after a 24-h fast, during an insulin infusion of 20 mU x kg(-1) x min(-1). Glucose levels were measured at baseline and every 10 min during the clamp. Insulin levels were measured at baseline and at the end of the clamp study. Glucose infusion rates (GIRs) during the last 30 min of the clamp study were in a steady state. Tritiated glucose infusion was used to measure rates of endogenous glucose output (EGO) both at baseline and during steady-state euglycemia. Glucose disposal rates (GDRs) were computed from the GIR and EGO. Fasting and steady-state glucose and insulin levels were comparable in the 3 groups of mice. No differences in fasting EGO were noted between the groups. GIR was significantly reduced (37%, P = 0.001) in the eNOS knockout (KO) mice compared with the WT mice, with values for the nNOS mice being intermediate. EGO was completely suppressed in the nNOS and WT mice during insulin infusion, but not in the eNOS mice. Even so, the eNOS mice displayed significantly reduced whole-body GDRs compared with those of the WT mice (82.67+/-10.77 vs. 103.67+/-3.47 mg x kg(-1) x min(-1), P = 0.03). eNOS KO mice are insulin resistant at the level of the liver and peripheral tissues, whereas the nNOS KO mice are insulin resistant only in the latter. These data indicate that NO plays a role in modulating insulin sensitivity and carbohydrate metabolism and that the eNOS isoform may play a dominant role relative to nNOS.

Animals↗

PubMed2000

Effects of captopril treatment of renovascular hypertension on beta-adrenergic modulation of L-type Ca(2+) current.

beta-Adrenergic stimulation of cardiac L-type Ca(2+) channels is severely impaired in hypertrophied and failing hearts of both experimental animals and humans. The aim of this study was to test the hypothesis that chronic treatment of renovascular hypertension with captopril restores normal beta-adrenergic responsiveness of L-type Ca(2+) channels in cardiac myocytes. Left ventricular hypertrophy was induced in rabbits by unilateral renal artery banding and contralateral nephrectomy. Beginning at 3 months after banding, hypertensive rabbits were treated with captopril for 3 months. The responsiveness of L-type Ca(2+) current (I(Ca,L)) to (+/-)-isoproterenol was investigated with the whole-cell patch-clamp technique. (+/-)-Isoproterenol (1 microM) induced an increase of I(Ca,L) at 0 mV of 126 +/- 20% (n = 13) in control myocytes versus 69 +/- 11% (n = 18) in hypertrophied myocytes from rabbits 3 months after banding. The half-maximal activation concentration of (+/-)-isoproterenol was similar between control and hypertrophied myocytes. Forskolin (10 microM) induced a similar percentage of increase of I(Ca,L) in control and hypertrophied myocytes, 109 +/- 13% (n = 12) versus 120 +/- 14% (n = 11) at 0 mV. The responsiveness of I(Ca,L) to (+/-)-isoproterenol remained depressed in untreated hypertensive rabbits. (+/-)-Isoproterenol (1 microM) increased I(Ca, L) at 0 mV by 64 +/- 8% (n = 14) in myocytes isolated from rabbits 6 months after banding versus 111 +/- 15% (n = 16) in age-matched controls. In captopril-treated rabbits, 1 microM (+/-)-isoproterenol increased I(Ca,L) by 110 +/- 11% (n = 17). We conclude that the maximal response of I(Ca,L) to (+/-)-isoproterenol was severely depressed in hypertrophied myocytes. Chronic treatment of renovascular hypertension with captopril can restore normal responsiveness of I(Ca,L) to (+/-)-isoproterenol in cardiac myocytes.

Animals↗

PubMed2000

The proteasome controls the expression of a proliferation-associated nuclear antigen Ki-67.

The proteasome is a protease complex responsible for rapid, selective, and irreversible removal of regulatory proteins, as well as many other cellular proteins. In this study, we have demonstrated that a proliferation-associated nuclear protein Ki-67 depended on the proteasome for its rapid degradation. A proteasome-specific inhibitor lactacystin augmented Ki-67 protein levels in pancreatic cancer BxPC-3 cells while repressed the level of steady-state Ki-67 mRNA. Inhibition of the proteasome also led to accumulation of two CDK inhibitors p27(kip1) and p21(cip1) in the BxPC-3 cells. Failed reduction of Ki-67 protein and enhanced levels of the two CDK inhibitors are likely contributing factors for the suppressed BxPC-3 proliferation after proteasome inhibition.

Acetylcysteine↗

PubMed2000

Novel Single- and Double-Layer and Three-Dimensional Structures of Rare-Earth Metal Coordination Polymers: The Effect of Lanthanide Contraction and Acidity Control in Crystal Structure Formation.

Lanthanide atom sizes (the lanthanide contraction) directly control the type of structure formed by the coordination of a single multidentate ligand, 3,5-pyrazoledicarboxylic acid (H(3)pdc). Single-layer, double-layer ([Eu(2)(Hpdc)(3)(H(2)O)(6)], see picture), and three-dimensional networks were found. Control of the reaction pH plays a key role in the structure formation in this system.

Journal Article↗

PubMed2000

A binary vector-based large insert library for Brassica napus and identification of clones linked to a fertility restorer locus for Ogura cytoplasmic male sterility (CMS).

We constructed and characterized a large DNA insert library for Brassica napus that would facilitate genome-related research and map-based cloning efforts in Brassica species. This library, consisting of 92,160 clones arrayed in 384-well microtiter dishes, was based on a conventional plant transformation vector (binary vector), and was constructed using a single ligation with transformation efficiency of over 5000 recombinants per microliter of ligation mixture. Every clone in this library contains an insert in the size range of 30-190 kb, facilitating both chromosome walking and plant transformation. Screening this library with three DNA markers (C2, F10, and CabR) that are linked to a fertility restorer locus for Ogura cytoplasmic male sterility (CMS) identified at least 17 positive clones for each probe. Among the 17 positive clones identified by C2, nine are linked to the restorer locus. Marker F10 identified 21 clones, of which only two are linked to the restorer locus. None of 68 clones identified by CabR is linked to the restorer locus. A stability test using two clones identified by the C2 marker indicated that large DNA inserts are stable in this conventional vector in both Escherichia coli and Agrobacterium.

Agrobacterium tumefaciens↗

PubMed2000

Mutation analysis of BRCA1 gene in African-American patients with breast cancer.

An estimated 7% of all breast cancers and 10% of all ovarian cancers are associated with inherited mutations in BRCA1 and BRCA2 genes. The mutations of a breast cancer-susceptible gene, BRCA1, confers increased risk of breast cancer in young women. Numerous studies have reported specific mutations in the BRCA1 and BRCA2 genes in the white population. However, there are very few studies on African-American and other ethnic minority groups. The goal of this study is to identify whether African-American patients with breast cancer carry some common mutations reported in other ethnic groups and whether they carry some novel mutations. We screened hot-region mutations on exons 2, 5, 11, 16, and 20 of BRCA1 gene in 54 African-American patients with breast cancer by NIRCA and SSCP methods. Our data revealed one novel frameshift mutation (3331 insG) and three missense sequence variants (A3537G, A3667G, and C4009T) on exon 11. Each sequence change was confirmed by automatic DNA sequencing. One rare sequence variant, A3537G, has been revealed in high frequency (3/54). Our data suggested that African-American patients with breast cancer carry some unique BRCA1 gene mutations.

Black People↗

PubMed2000

Molecular strategies for improving waterlogging tolerance in plants.

Plants, like animals, are obligate aerobes, but due to their inability to move, have evolved adaptation mechanisms that enable them to survive short periods of low oxygen supply, such as those occurring after heavy rain or flooding. Crop plants are often grown on soils subject to waterlogging and many are sensitive to waterlogging of the root zone. The combination of unfavourable weather conditions and suboptimal soil and irrigation techniques can result in severe yield losses. The molecular basis of the adaptation to transient low oxygen conditions has not been completely characterized, but progress has been made towards identifying genes and gene products induced during low oxygen conditions. Promoter elements and transcription factors involved in the regulation of anaerobically induced genes have been characterized. In this paper an account is presented of the molecular strategies that have been used in an attempt to increase flooding tolerance of crop plants.

Adaptation, Physiological↗

PubMed2000

[Long-term effects of low-dose combined norethisterone and combined 18-metayl-norethisterone on lipid metabolism in healthy women].

OBJECTIVE: To assess the long-term effects of combined oral contraceptive pills use on the mean of serum TG, TC, HDL-C, LDL-C, ApoA1, ApoB and Lp(a). METHODS: The study was carried out in 446 women grouped as combined norethisterone containing ethinylestradiol (EE) 35 micrograms and norethisterone 625 micrograms; combined 18-metayl-norethisterone (norgestrel) containing EE 30 micrograms and 18-metayl-norethisterone 300 micrograms for using 5-25 years, and control subjects wearing IUD for the corresponding period. The three groups were similar in age, body mass index (BMI), continued period of contraceptives use and income. RESULTS: The data showed that changes of varying degree of lipid and lipoprotein parameters were obvious in women of long-term taking low-dose combined norethisterone and norgestrel, compared with the control. The mean of TG, HDL-C, ApoA1 were significantly increased simultaneously (P < 0.05, P < 0.01), indicated multiple effects of two low-dose Chinese COCs on lipid lipoprotein parameters. In addition, A significant increase (P < 0.05) in Lp(a), an independent risk factor for cardiovascular disease, was found in norgestrel group. Further more, the results of stratified analysis to duration of contraceptives use showed that the mean of TC, LDL-C, in the combined norethisterone use less than 15 years, after the adjusting for age, were significantly lower (P < 0.05, P < 0.01) and the ratio of LDL-C/HDL-C was improved (P < 0.05), compared with the Norgestrel; at the same time, the mean of ApoA1 was markedly higher (P < 0.05) in combined norethisterone; the ratio of ApoA1/ApoB (1.87 +/- 0.58) in the combined norethisterone group was superior to the ratio value (1.68 +/- 0.55) in norgestrel group. CONCLUSIONS: These beneficial effects on lipid metabolism have been considered indicators of potential cardiovascular protective effect of the combined norethisterone for taking pill less than 15 years, but these protective effects would be reduced with adverse change in lipid and lipoprotein parameters for taking combined norethisterone more than 15 years. In contrast, the mean of TC, LDL-C, two known risk factors for cardiovascular system, in the norgestrel use less than 15 years, after the adjusting for age, were significantly increased (P < 0.05, P < 0.01), and adverse changes in the TC/HDL-C ratio (P < 0.05) and ASI value, compared with the combined norethisterone; Lp(a) level was markedly higher in the norgestrel group than that in the control group (P < 0.05). These adverse effects on lipid metabolism have been considered indicators of potential cardiovascular harmful effect of low-dose norgestrel.

Adult↗

PubMed2000

[Clinical application of extended resection of Vater's papilla].

OBJECTIVE: To report the surgical technique and clinical application of extended resection of Vater's papilla (ERVP). METHODS: ERVP was performed in 12 selected patients with tumors of ampulla of Vater according to the following criteria: (1) no signs of distant mestastasis before operation; (2) no hepatic and peritoneal mestastasis during exploration, frozen section of peripancreas-duodenal lymph nodes being negative; (3) tumor less than 2 cm in diameter, pathologic examination of tumor being adenocarcinoma or adenoma; (4) pathologic examination of edge of resection being negative. RESULTS: There was no operative death nor complications in 12 cases treated by ERVP. The average time of operation was 2.3 hours, the average amount of blood infused was 433 ml, and the average time of hospitalization was 15.8 days. In 5 of 10 cases of Vater's ampullary adenocarcinoma, the mean survival time was 42 months (36-62 months). The remaining 5 cases are still alive at 20-64 months. Two patients with Vater's ampullary adenoma still survive at 32 and 46 months, respectively. CONCLUSION: ERVP is easy to perform with comparatively less surgical trauma and complication, but redical excision of tumor is not easy. It may be particulary indicated for older and high-risk patients, or patients with cancer less than 2 cm in diameter.

Adenocarcinoma↗

PubMed2000

[Genetic analysis of hereditary factor VII deficiency from a Chinese pedigree].

OBJECTIVE: To identify the mutation in coagulation factor VII gene from a Chinese patient with hereditary coagulation factor VII deficiency. METHODS: The genomic DNA fragments of FVII gene from a propositus and normal subjects were amplified using polymerase chain reaction (PCR), and analyzed with direct sequencing of PCR products. The PCR amplified genomic DNA fragments of FVII gene from the propositus and her family members were analyzed using restriction enzyme Hgic I. RESULTS: The FVII gene sequences of normal subjects were identical to the data published, while a missense mutation (TGT-->GGT) was found at codon 329 in FVII gene of the propositus. The heterozygous condition for the mutation was revealed in her three family members. CONCLUSION: We have found a novel mutation (TGT-->GGT) at codon 329 in FVII gene of a patient with hereditary FVII deficiency, which leads to a cystein residue replaced by a glysine. PCR combined with restriction enzyme Hgic I digestion would be a rapid diagnostic method for this mutation.

Factor VII↗

PubMed2000

Molecular genetic analysis and mutation screening of the VHL gene in a Japanese family with von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited familial cancer syndrome which predisposes individuals to a variety of malignant and benign tumors. Its penetrance is almost 100% by 61-70 years of age. We have identified a germline mutation in the VHL gene of a Japanese male patient with a retinal hemangioma in the left eye, an intracranial hemangioblastoma, a left renal tumor and bilateral pheochromocytomas. Screening for the mutation was performed in all members of the patient's family at risk for VHL disease. The mutation identified in the patient was a missense mutation at codon 238 (CGG to CAG). The elder daughter, who did not show any clinical symptoms, was found to carry the same mutation. In order to detect and treat tumors in VHL patients at an earlier stage, it is necessary to identify and screen for the VHL gene mutation in all family members known at risk.

Adult↗