Biomedical subjects

K Koyama

Publications and source records attributed to K Koyama.

At least 37 records · Page 2Linked to original sources

PubMed2001

Mono(ADP-ribosyl)ation of 2'-deoxyguanosine residue in DNA by an apoptosis-inducing protein, pierisin-1, from cabbage butterfly.

Pierisin-1 is a potent apoptosis-inducing protein derived from the cabbage butterfly, Pieris rapae. It has been shown that pierisin-1 has an A small middle dotB structure-function organization like cholera or diphtheria toxin, where the "A" domain (N-terminal) exhibits ADP-ribosyltransferase activity. The present studies were designed to identify the target molecule for ADP-ribosylation by pierisin-1 in the presence of beta-[adenylate-(32)P]NAD, and we found DNA as the acceptor, but not protein as is the case with other bacteria-derived ADP-ribosylating toxins. ADP-ribosylation of tRNAs from yeast was also catalyzed by pierisin-1, but the efficiency was around 110 of that for calf thymus DNA. Pierisin-1 efficiently catalyzed the ADP-ribosylation of double-stranded DNA containing dG small middle dotdC, but not dA small middle dotdT pairs. The ADP-ribose moiety of NAD was transferred to the amino group at N(2) of 2'-deoxyguanosine to yield N(2)-(alpha-ADP-ribos-1-yl)-2'-deoxyguanosine and its beta form, which were determined by several spectral analyses including (1)H- and (13)C-NMR and mass spectrometry. The chemical structures were also ascertained by the independent synthesis of N(2)-(D-ribos-1-yl)-2'-deoxyguanosine, which is the characteristic moiety of ADP-ribosylated dG. Using the (32)P-postlabeling method, ADP-ribosylated dG could be detected in DNA from pierisin-1-treated HeLa cells, in which apoptosis was easily induced. Thus, the targets for ADP-ribosylation by pierisin-1 were concluded to be 2'-deoxyguanosine residues in DNA. This finding may open a new field regarding the biological significance of ADP-ribosylation.

ADP Ribose Transferases↗

PubMed2001

Phenanthroindolizidine alkaloids as cytotoxic substances in a Danaid butterfly, Ideopsis similis, against human cancer cells.

We previously reported the presence of cytotoxic substances in extracts of the Danaid butterfly, Ideopsis similis. In the present study, we isolated cytotoxic substances against a human gastric cancer cell line, TMK-1, in I. similis pupae, with an activity similar to that of the adult butterfly. The basic fraction, prepared from a methanol extract, accounted for 83% of the cytotoxic activity. Two major cytotoxic substances were purified by HPLC, and one was determined to be a new phenanthroindolizidine alkaloid, trans-(+)-3,14alpha-dihydroxy-6,7-dimethoxyphenanthroindolizidine (1), and the other a known compound, trans-(+)-3,14alpha-dihydroxy-4,6,7-trimethoxyphenanthroindolizidine (2). The IC(50) values for TMK-1 cells were 0.5 ng/mL and 0.7 ng/mL, respectively. These two compounds showed similar cytotoxic potential with four other cancer cell lines including cervical, lung, and colon carcinomas and leukemia. Quantitative analyses indicated the presence of each of the two phenanthroindolizidine alkaloids at levels of 11-74 microg in each larva, pupa, or adult of I. similis. However, 1 was not detected in the leaves of Tylophora tanakae, a host plant for larvae of I. similis, and the level of 2 (2 microg per gram of leaves) was far less than that in the larvae. Since the leaves of T. tanakae are known to contain various phenanthroindolizidines, compounds 1 and 2 are presumably metabolically converted from such alkaloids in larvae of I. similis.

Alkaloids↗

PubMed2001

Distinct roles for the N- and C-terminal regions in the cytotoxicity of pierisin-1, a putative ADP-ribosylating toxin from cabbage butterfly, against mammalian cells.

Pierisin-1 is an 850-aa cytotoxic protein found in the cabbage butterfly, Pieris rapae, and has been suggested to consist of an N-terminal region with ADP-ribosyltransferase domain and of a C-terminal region that might have a receptor-binding domain. To elucidate the role of each region, we investigated the functions of various fragments of pierisin-1. In vitro expressed polypeptide consisting of amino acid residues 1-233 or 234-850 of pierisin-1 alone did not show cytotoxicity against human cervical carcinoma HeLa cells. However, the presence of both polypeptides in the culture medium showed some of the original cytotoxic activity. Introduction of the N-terminal polypeptide alone by electroporation also induced cell death in HeLa cells, and even in the mouse melanoma MEB4 cells insensitive to pierisin-1. Thus, the N-terminal region has a principal role in the cytotoxicity of pierisin-1 inside mammalian cells. Analyses of incorporated pierisin-1 indicated that the entire protein, regardless of whether it consisted of a single polypeptide or two separate N- and C-terminal polypeptides, was incorporated into HeLa cells. However, neither of the terminal polypeptides was incorporated when each polypeptide was present separately. These findings indicate that the C-terminal region is important for the incorporation of pierisin-1. Moreover, presence of receptor for pierisin-1 in the lipid fraction of cell membrane was suggested. The cytotoxic effects of pierisin-1 were enhanced by previous treatment with trypsin, producing "nicked" pierisin-1. Generation of the N-terminal fragment in HeLa cells was detected after application of intact entire molecule of pierisin-1. From the above observations, it is suggested that after incorporation of pierisin-1 into the cell by interaction of its C-terminal region with the receptor in the cell membrane, the entire protein is cleaved into the N- and C-terminal fragments with intracellular protease, and the N-terminal fragment then exhibits cytotoxicity.

ADP Ribose Transferases↗

PubMed2001

Phase I/II study of intravenous nedaplatin and intraarterial cisplatin with transcatheter arterial embolization for patients with locally advanced uterine cervical carcinoma.

BACKGROUND: Nedaplatin, a platinum analog with less renal toxicity and similar efficacy for cervical carcinoma, recently has been shown to have a synergistic effect on cervical carcinoma lines in combination with cisplatin. To determine the clinical efficacy of this combination in patients with cervical carcinoma, the authors conducted a Phase I/II study of intravenous nedaplatin and intraarterial cisplatin combined with transcatheter arterial embolization (TAE). METHODS: Eligibility criteria were as follows: cervical carcinoma (Stages IB2-IV; International Federation of Gynecology and Obstetrics), 16-70 years of age, performance status between 0 and 2, and adequate bone marrow, renal, and hepatic function. Nedaplatin (40-70 mg/m2) was administered intravenously on Day 1 followed by intraarterial administration of cisplatin (70 mg/m2) on Day 3 via both uterine arteries by using the Seldinger method. This then was followed by TAE. This course of treatment was repeated every 3 weeks for 3 cycles. RESULTS: Patient data were as follows: age 37-68 (median, 55 years) and Stages IB2:4, IIA:3, IIB:2, IIIA:1, IIIB:3, IVA:2 carcinoma. The response to therapy was defined by magnetic resonance imaging as follows: partial response in 60% (9 of 15) of patients, complete response in 40% (6 of 15) of patients, and an overall response rate of 100% (95% confidence interval, 78-100%). Myelosuppression was manageable. Grade 3/4 renal toxicity was observed in 2 patients who received 70 mg/m2 of nedaplatin. Thirteen patients received radical hysterectomy, 1 patient received lymph node sampling, and 11 patients received adjuvant radiotherapy or chemotherapy. CONCLUSIONS: The maximum tolerable dose was 70 mg/m2 nedaplatin, and the dose-limiting toxicity was renal toxicity. The recommended dose was 60 mg/m2 nedaplatin intravenously followed by 70 mg/m2 cisplatin intraarterially. Intravenous nedaplatin followed by intraarterial cisplatin with TAE appears to be very effective for locally advanced cervical carcinoma.

Adult↗

PubMed2001

Positron emission tomography with (18)F-fluorodeoxyglucose of uterine sarcoma: a comparison with magnetic resonance imaging and power Doppler imaging.

OBJECTIVE: The effectiveness of positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) for diagnosis of uterine sarcoma was evaluated in comparison to the effectiveness of magnetic resonance (MR) imaging and power Doppler imaging. METHOD: The cases of five Osaka City University Hospital patients diagnosed with uterine sarcoma based on histopathological examination, in whom FDG-PET, MR imaging, and power Doppler imaging studies had been performed preoperatively, were reviewed. A comparative study of the usefulness of these three imaging modalities for diagnosis of sarcoma was conducted. Tumors comprised three leiomyosarcomas, one endometrial stromal sarcoma, and one carcinosarcoma. RESULTS: FDG-PET examinations were 100% positive for the five sarcomas; MR imagings were 80% positive (four of five cases), and US was 40% positive (two of five cases). The mean standardized uptake value of the sarcomas was 4.5 +/- 1.3. CONCLUSION: The sarcoma lesions were clearly imaged by FDG-PET. FDG-PET may be a most useful diagnostic method for uterine sarcoma.

Aged↗

PubMed2001

Intralobular heterogeneity of oxidative stress and cell death in ischemia-reperfused rat liver.

The relationship between zonal oxidative stress and cell death after ischemia-reperfusion injury in rat liver was investigated. Oxidative stress was detected in situ by perfusion with nitroblue tetrazolium, which is converted to insoluble blue formazan by reducting agents. Cell death was detected in situ by perfusion with trypan blue. When isolated liver was perfused after 30 or 60 min of warm ischemia, oxidative stress was detected in periportal parenchymal cells after 30 min of reperfusion. It spread in the shape of a doughnut to midzonal cells after 60 min of reperfusion. On the other hand, cell death was observed in parenchymal cells that were within the doughnut-like area in which oxidative stress was detected. The extent of oxidative stress and cell death was higher after 60 min of ischemia than after 30 min of ischemia. In nonparenchymal cells, oxidative stress was observed in midzonal and pericentral regions after only 12 min of reperfusion, but minor cell death was observed only in periportal and midzonal regions after 30 min of reperfusion. Administration of allopurinol, an inhibitor of xanthine oxidase, suppressed oxidative stress and cell death in periportal parenchymal cells. These findings indicate that periportal and midzonal parenchymal cell death can be caused by zone-specific and xanthine-oxidase-mediated oxidative stress in parenchymal cells.

Allopurinol↗

PubMed2001

Adenocarcinoma at the site of ileoanal anastomosis in Crohn's disease: report of a case.

PURPOSE: Proctocolectomy with ileoanal anastomosis has gained acceptance for the treatment of patients with ulcerative colitis. However, there are some patients with Crohn's disease who received ileoanal anastomosis, because some Crohn's colitis is difficult to differentiate from ulcerative colitis. The risk of cancer development at the site of ileoanal anastomosis has not been emphasized in Crohn's disease. METHODS: A 12-year-old patient with Crohn's disease was treated by proctocolectomy with straight ileoanal anastomosis. Twenty-five years after the operation, the patient noticed the tumor that developed at the site of ileoanal anastomosis. RESULTS: This article presents a patient with Crohn's disease who developed invasive adenocarcinoma at the site of ileoanal anastomosis 25 years after proctocolectomy with ileoanal anastomosis. CONCLUSIONS: An ileoanal anastomosis does not eliminate the risk of cancer development, and surveillance after this operation seems advisable.

Adenocarcinoma↗

PubMed2001

Diagnostic usefulness of FDG PET for pancreatic mass lesions.

UNLABELLED: The purpose of this study was to investigate the feasibility of [18F]2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) in patients with a pancreatic mass by comparing the results with those of X-ray computed tomography (CT) and magnetic resonance (MR) imaging. METHODS: Eighty-six patients with pancreatic lesions, included 65 malignant tumors and 21 benign masses (55 masses were proven histologically and the others were diagnosed clinically), were studied. The diagnostic factors of CT and MR imaging were evaluated, and those of FDG PET were also evaluated for malignant and benign masses by visual interpretation and quantitative interpretation with the standardized uptake value (SUV) and SUVgluc which was designed to reduce the effects of a high blood sugar level. Visual interpretations were evaluated only in FDG PET images, and quantitative interpretations were evaluated by referring to CT and/or MR imaging. The correlation between SUV and the degree of histological differentiation in pancreatic ductal adenocarcinoma was investigated. RESULTS: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for CT imaging were 91, 62, 88, 68 and 84%, and for MR imaging 78, 70, 88, 54 and 76%, respectively. In visual interpretation of FDG PET images, the sensitivity, specificity, PPV, NPV and accuracy were 82, 81, 93, 59 and 81%, respectively. Significant differences between malignant and benign lesions existed in SUV and SUVgluc (p < 0.0001, each). With the cutoff value of SUV as 2.1 and SUVgluc as 2.2, the accuracy of diagnosis was maximal. With that cutoff value, the sensitivity, specificity, PPV, NPV and accuracy for SUV were 89, 76, 92, 70 and 86%, and for SUVgluc 91, 76, 92, 73 and 87%, respectively. The sensitivity and NPV of SUVgluc were higher than those of SUV, which suggests that SUVgluc may be more useful in reducing the number of overlooked malignant tumors. The specificity and PPV of FDG PET were superior to those of CT and MR imaging. There were no significant differences between the SUVs of moderately differentiated adenocarcinomas and those of well differentiated adenocarcinomas. CONCLUSION: To improve the diagnostic procedure for classifying masses, FDG PET with not only SUV but also SUV corrected by the blood sugar level is required in addition to morphological diagnosis by CT and/or MR imaging.

Aged↗

PubMed2001

Physiological FDG uptake in the palatine tonsils.

In clinical F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) studies of the head and neck region, remarkable symmetric tonsillar FDG uptake is sometimes observed. We determined the incidence and degree of tonsillar FDG uptake and investigated the significance of tonsillar FDG uptake. Between June 1998 and August 1998, we obtained informed consent from 17 patients who were scheduled to undergo a FDG-PET study for their own disease (11 men and 6 women; aged 22 to 77 yr) and who did not have head and neck disease to perform FDG-PET scanning of the head and neck region in addition to their target organs. The incidence and degree of tonsillar FDG uptake were determined. Remarkable tonsillar FDG uptake was found in 9 patients. The SUVs of these FDG uptakes ranged from 2.48 to 6.75, with a mean of 4.29 +/- 1.20 (SD). Tonsillar FDG uptakes in the remaining 8 patients were not remarkable, and their SUVs ranged from 1.93 to 3.31, with a mean of 2.46 +/- 0.45. Head and neck disease does not appear to have been responsible for the increase in tonsillar FDG uptake. Differences among tonsillar FDG uptake in these 17 patients without head and neck disease appear to reflect differences in activity of "physiological" inflammation of the palatine tonsils.

Adult↗

PubMed2001

Alternating myocardial sympathetic neural function of athlete's heart in professional cycle racers examined with iodine-123-MIBG myocardial scintigraphy.

Myocardial sympathetic neural function in professional athletes who had the long-term tremendous cardiac load has not been fully investigated by myocardial iodine-123-metaiodobenzylguanidine (MIBG) uptake in comparison with power spectral analysis (PSA) in electrocardiography. Eleven male professional cycle racers and age-matched 11 male healthy volunteers were enrolled in this study. The low frequency components in the power spectral density (LF), the high frequency components in the power spectral density (HF), the LF/HF ratio and mean R-R interval were derived from PSA and time-domain analysis of heart rate variability in electrocardiography. The mean heart-to-mediastinum uptake ratio (H/M ratio) of the MIBG uptake, in professional cycle racers was significantly lower than that in healthy volunteers (p < 0.01) and HF power in professional cycle racers was significantly higher than that in healthy volunteers (p < 0.05). In the group of professional cycle racers, the H/M ratio showed a significant correlation with the R-R interval, as indices of parasympathetic nerve activity (r = 0.80, p < 0.01), but not with the LF/HF ratio as an index of sympathetic nerve activity. These results may indicate that parasympathetic nerve activity has an effect on MIBG uptake in a cyclist's heart.

3-Iodobenzylguanidine↗

PubMed2001

Usefulness of dual-head coincidence gamma camera with thick NaI crystals for nuclear oncology: comparison with dedicated PET camera and conventional gamma camera with thin NaI crystals.

AIM: A comparative study of the images obtained with a dual-head coincidence gamma camera with thick NaI crystals (19 mm), a dedicated PET camera with BGO crystals and a conventional gamma camera with thin NaI crystals (9.5 mm) was conducted to clarify the clinical feasibility of a dual-head coincidence gamma camera with thick NaI crystals. METHODS: FDG images of 27 patients with malignant tumors were obtained by means of a dual-head coincidence gamma camera with thick NaI crystal and a dedicated PET camera with BGO crystals. The images of bone scintigraphy in 10 cancer patients obtained with the dual-head coincidence gamma camera were compared with those taken by a conventional dual-head gamma camera with thin NaI crystals. RESULTS: Patient-basis sensitivity in 27 patients with neoplasms and lesion-basis sensitivity of the dual-head coincidence gamma camera and the dedicated PET camera were 74.1% and 85.2% (n.s.), 66.7% and 72.2% (n.s.), respectively. The tumor to background FDG uptake ratio derived from the coincidence gamma camera was significantly lower than that derived from the dedicated PET camera (mean +/- s.d.; 3.48 +/- 3.77 vs. 8.12 +/- 8.92, p < 0.0001), but the tumor to background FDG uptake ratio obtained with both methods correlated well (r = 0.84, p < 0.001). Similar whole body bone scans were obtained with the dual-head coincidence gamma camera and the conventional dual-head gamma camera in all 10 patients. CONCLUSION: These results suggest that the dual-head coincidence gamma camera with thick NaI crystals has potentially high clinical applicability for community hospitals.

Adult↗

PubMed2001

Genetic analysis of a variant luteinizing hormone in an infertile woman.

In a woman with infertility and an endometrial polyp, we analyzed the nucleotide sequence of the beta-subunit of her luteinizing hormone which showed anomalous immunogenecity in that it was recognized by time resolved-fluoroimmunoassay but not by immunoradiometric assay. The sequence analysis showed two substitutional mutations of beta-subunit Trp (TGG) to Arg (CGG) and Ile (ATC) to Thr (ACC). The variant luteinizing hormone might have had some relation to the infertility and the endometrial polyp. been described [2, 4, 13-15]. Although the role of the variant LH is still unclear, it has different biologicl activity as compared to normal LH and may play a role in causing infertility, menstrual disorder, endometriosis and spontaneous miscarriage [1, 3, 4, 9, 10, 17]. We now report a study of the DNA sequence of beta-subunit of anomalous LH in an infertile patient with an endometrial polyp.

Adult↗

PubMed2001

Comparative studies on the levels of serum IgG1 and IgG2a in susceptible B10.BR mice infected with different strains of the intestinal nematode parasite Trichuris muris.

Comparative studies were carried out on the levels of serum IgG1 and IgG2a in susceptible B10.BR mice infected with different strains of Trichuris muris (E-J and S strains). As infection proceeded, levels of IgG1 and IgG2a increased in mice infected with either strain until at least day 32 post-infection (p.i.). There were no differences in the IgG1 levels on days 14, 20, and 25 p.i. between mice infected with either E-J or S strain, whereas IgG2a levels on days 20, 25, and 32 p.i. were higher in S-infected mice than those in E-J-infected mice. Isotype switching to IgG2a is entirely dependent on interferon gamma (IFN-gamma) and, according to our previous results, the period of high IFN-gamma production in S-infected B10.BR mice is long compared to E-J-infected B10.BR mice. Thus, increased levels of IFN-gamma may sustain high levels of serum IgG2a in S-infected mice. Taken together, levels of serum IgG2a are useful markers of IFN-gamma production in T. muris infection.

Animals↗

PubMed2001

Colon cancer in rectal bladder.

A large number of patients have been reported with colon cancers following ureterosigmoidostomy, created after total cystectomy. However, there have been few reports of cancer in rectal bladder created instead of ureterosigmoidostomy to reduce the risk of cancer development. We report a case of colon cancer that developed in the rectal bladder 6 years after the operation. A 77-year-old man presented with blood in stools. Colonoscopy revealed a cancer adjacent to the urine inlet to the colonic lumen in rectal bladder. At laparotomy. the cancer was recognized in the rectal bladder. with invasion to the pubic bone. A palliative resection of the rectal bladder, and creation of sigmoid colostomy and ileal conduit were performed. Histologic examination confirmed moderately differentiated adenocarcinoma, which was considered to have originated from the colonic mucosa in the rectal bladder. Colonic mucosa has an increased risk of cancer development after continuous exposure to urine. It is important for gastroenterologists to perform surveillance colonoscopy in patients with urinary diversion into the colon.

Adenocarcinoma↗

PubMed2001

Small bowel perforation caused by metastasis from an extra-abdominal malignancy: report of three cases.

Small bowel perforation is rarely caused by metastasis from an extra-abdominal malignancy. This report describes three cases of small bowel perforation that occurred secondary to a metastatic tumor. The first case involved a 72-year-old man with malignant lymphoma of the larynx that had been treated with chemo- and radiation therapy; the second involved a 70-year-old man with rhabdomyosarcoma of the mediastinum that had been treated with radiation therapy; and the third involved a 41-year-old man with lung carcinoma that had been treated with surgery 10 months prior to perforation. Each patient presented with acute abdominal pain, had X-ray findings of free air in the abdomen, and underwent limited emergency surgery. Wedge resection and closure of the ileum was performed for the first patient and partial bowel resection with the creation of an intestinal stoma was performed for the second and third patients. In each case, the histologic findings of the resected specimens were consistent with the extra-abdominal primary tumors. Although the patients recovered sufficiently to begin eating and moving about, all three died of cancer or cancer-related complications within 45 days of surgery. We conclude that surgeons should be aware of the poor prognosis of such patients and perform only the minimal surgery required.

Adult↗

PubMed2001

Laparascope-assisted versus conventional restorative proctocolectomy with rectal mucosectomy.

To assess the advantages of a laparoscope-assisted proctocolectomy with ileal J-pouch anal anastomosis compared with conventional procedures, we retrospectively analyzed the results of the two procedures as follows: Eleven patients including five patients with familial adenomatous polyposis (FAP) and six with ulcerative colitis (UC) underwent a laparoscope-assisted proctocolectomy and hand-sewn ileal J-pouch anal anastomosis at our department from June 1997 to November 1999. This laparoscope-assisted colectomy (LAC) group was then compared with a group of 13 patients who had undergone conventional ileal pouch anal anastomosis using a standard laparotomy from 1986 to 1997. The median operative time of the LAC group was 8h 23min, which was 81 min longer than that of the standard colectomy (SC) group. The number of days during which eating was prohibited were similar in the two groups but the median postoperative hospital stay was significantly shorter in the LAC group (24.1 days). In the LAC group, the small incisions showed better cosmetic results and there was also a remarkable reduction in the degree of postoperative pain. In conclusion, a laparoscope-assisted proctocolectomy with ileal J-pouch anal anastomosis can be employed widely in patients with FAP and also in selected patients with UC.

Adenomatous Polyposis Coli↗

PubMed2001

Reattachment of the greater trochanter using the Dall-Miles cable grip system in revision hip arthroplasty.

Clinical and radiographic results of trochanteric osteotomy after revision hip arthroplasty in 62 hips were reviewed. The osteotomized fragment had been reattached using the Dall-Miles cable grip system in each hip. The patients' average age at operation was 64.4 years (range, 40-86 years). The average duration of follow-up was 30.0 months (range. 12-60 months). Trochanteric nonunion was found in 19 hips (30.6%). Trochanteric nonunion developed in 14 (38.9%) of 36 hips with each cable attached around the medial cortex bone, in 2 (16.7%) of 12 hips with each cable passed in a drill hole, and in 3 (21.4%) of 14 hips with one cable passed through a hole and the other attached around the medial cortex. Fragmentation developed in 18 hips (29.0%). In 3 of these 18, the fragments had migrated close to the acetabular component. Cable breakage was seen in 4 hips (6.5%), and bone absorption around the cable in the medial cortex was seen in 17 hips (27.4%). There were 16 hips (25.8%) that presented symptoms at the greater trochanter, including spontaneous pain and tenderness. When the Dall Miles cable grip device is used for reattachment of the greater trochanter, attention should be paid to the condition of the trochanteric bed, the tension of the abductor muscles, and to the placement of the cables and the H-shaped grip.

Adult↗

PubMed2001

VNTR sequence on human chromosome 11p15 that affects transcriptional activity.

We found a variable number of tandem repeat (VNTR) sequence with 38-bp repetitive units in the promoter region of a gene of unknown function on human chromosome 11p15. Polymerase chain reaction amplification of this VNTR sequence using genomic DNA from 80 unrelated individuals revealed two common alleles, one with 10 (79% allelic frequency) and the other with 14 (14% allelic frequency) repetitive units, and two rare alleles with 22 (3%) or 30 (3%) repetitive units. We investigated whether differences in the length of this VNTR sequence would affect transcriptional activity of a heterologous promoter by transient transfection to NEC8, embryonal carcinoma cells derived from testis. The activity of the promoter was suppressed significantly when the VNTR region was cloned upstream, in a manner dependent on the number of repeats present in the VNTR sequence. The results implied that this polymorphic VNTR sequence might function as transcriptional regulator in 11p15, with differences in the number of repetitive units influencing efficiency of transcription of the gene lying downstream.

Alleles↗