Mitsuhiro Yoshinaga

HLA-A*26, HLA-B*4002, HLA-B*4006, and HLA-B*4801 Alleles Predispose to Adult T Cell Leukemia: The Limited Recognition of HTLV Type 1 Tax Peptide Anchor Motifs and Epitopes to Generate Anti-HTLV Type 1 Tax CD8+ Cytotoxic T Lymphocytes

Genetic risk for adult T cell leukemia (ATL) has been implicated by ethnic and familial segregation of ATL patients from HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). To clarify the genetic risk for ATL, we characterized HLA class I alleles of ATL patients and analyzed the anchor motifs of HTLV-1 peptides binding to HLA class I molecules, using 291 lines of anti-HTLV-1 CD8(+) cytotoxic T lymphocytes (CTLs) generated in vitro with a total of 165 synthetic peptides for HTLV-1 Tax and Env proteins. Allele frequencies of HLA-A*26, B*4002, B*4006, and B*4801 were significantly higher in ATL patients than in HAM/TSP patients and asymptomatic HTLV-1 carriers in southern Japan. CD8(+) CTL analysis revealed the HTLV-1 Tax peptide sequence to completely lack anchor motifs of peptides binding to HLA-A*26,B*4002, and B*4006 molecules but to possess one anchor for HLA-B*4801, while the HTLV-1 Env peptide sequence had many anchor motifs for HLA-A*26, B*4002, B*4006, and B*4801 molecules. Most ATL patients featured heterozygous HLA class I alleles composed of HLA-A*26, B*4002, B*4006, and B*4801, with a lower number of HTLV-1 Tax peptide anchor motifs and epitopes generating anti-HTLV-1 Tax CD8(+) CTLs than individuals possessing other HLA alleles. The relationship between Tax epitope and ATL incidence was verified by the significantly decreased number of HTLV-1 Tax epitopes in ATL patients compared with asymptomatic HTLV-1 carriers (p < 0.01) as well as late onset ATL patients (p < 0.001). These results indicate that HLA-A*26, B*4002, B*4006, and B*4801 alleles predispose to ATL because of the limited recognition of HTLV-1 Tax peptide anchor motifs and epitopes capable of generating anti-HTLV-1 Tax CD8(+) CTLs.

Precedence of the shift of body‐fat distribution over the change in body composition after menopause

Aim:  This study investigated the sequence of certain phenomena after menopause: decrease in bone mineral density (BMD), change in body composition (lean and fat components), and the shift toward upper body fat distribution.

Uterine lipoleiomyoma: A histopathological review of 17 cases

Lipoleiomyoma is a rare uterine tumor. The exact frequency and proliferation activity are not yet known. This study aims to know the frequency and evaluate the relation with renal angiomyolipoma. Lipoleiomyoma cases were immunohistochemically stained by antibodies for Ki‐67, melanoma specific antigen HMB45, S‐100 protein, and α smooth muscle actin (α‐SMA). Frequency of uterine lipoleiomyoma among  uterine  myomatous  tumor  was  17/4904  (0.35%)  in the Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School database (1983–2003). Patients ranged from 45 to 74 years of age, and 10 cases were associated with leiomyoma. Six of 17 (35%) cases showed areas with renal angiomyolipoma‐like vessels and atypical cellular features. Immunostaining was available in 12 cases. By Ki‐67 labeling index, both muscle (average 1.38%) and fat (average 1.17%) portions of the tumor had greater proliferation than normal myometrium (average 0.76%), which suggests that fat portions of the tumor are proliferating adipose tissue rather than fatty degeneration of muscular counterpart. HMB45 antigen, which is positive in renal angiomyolipoma, was negative in three uterine cases having angiomyolipoma‐like vessels (3/12). However, HMB45 antigen was positive in spindle‐shaped tumor cells of three cases (3/12) which lacked angiomyolipoma‐like vessels. Presence of angiomyolipoma‐like blood vessels in these tumors is not an uncommon feature. However, the diagnosis of uterine angiomyolipoma should not be based on the result of HMB45 antigen immunoreactivity alone.

Preoperative plasma osteopontin level as a biomarker complementary to carbohydrate antigen 125 in predicting ovarian cancer

Aim:  New biomarkers other than carbohydrate antigen (CA) 125 are needed for the detection of ovarian cancer. Osteopontin (OPN) is one of the candidates identified by high‐throughput complementary DNA microarray techniques. We evaluated the preoperative plasma OPN level as a diagnostic biomarker for ovarian cancer in comparison with CA125.

HTLV-1 provirus load in peripheral blood lymphocytes of HTLV-1 carriers is diminished by green tea drinking

Human T‐cell lymphotropic virus type 1 (HTLV‐1) is causatively associated with adult T‐cell leukemia (ATL) and HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since a high level of HTLV‐1 provirus load in circulating lymphocytes is thought to be a risk for ATL and HAM/TSP, diminution of HTLV‐1 provirus load in the circulation may prevent these intractable diseases. Our previous study (Jpn J Cancer Res 2000; 91: 34–40) demonstrated that green tea polyphenols inhibit in vitro growth of ATL cells, as well as HTLV‐1‐infected T‐cells. The present study aimed to investigate the in vivo effect of green tea polyphenols on HTLV‐1 provirus load in peripheral blood lymphocytes on HTLV‐1 carriers. We recruited 83 asymptomatic HTLV‐1 carriers to examine HTLV‐1 provirus DNA with or without administration of capsulated green tea extract powder. Thirty‐seven subjects were followed up for 5 months by measuring HTLV‐1 provirus load after daily intake of 9 capsules of green tea extract powder per day (equivalent to 10 cups of regular green tea), and 46 subjects lived ad libitum without intake of any green tea capsule. The real‐time PCR quantification of HTLV‐1 DNA revealed a wide range of variation of HTLV‐1 provirus load among asymptomatic HTLV‐1 carriers (0.2‐200.2 copies of HTLV‐1 provirus load per 1000 peripheral blood lymphocytes). Daily intake of the capsulated green tea for 5 months significantly diminished the HTLV‐1 provirus load as compared with the controls (P=0.031). These results suggest that green tea drinking suppresses proliferation of HTLV‐1‐infected lymphocytes in vivo.

Inguinal hernia containing functioning, rudimentary uterine horn and endometriosis.

BACKGROUND: Inguinal hernia containing uterus and endometriosis is exceedingly rare. Most inguinal endometriosis is located at an extrapelvic site near the round ligament. We report a case of a patient with inguinal hernia containing rudimentary uterine horn and endometriosis. CASE: A young, nulliparous, regularly menstruating woman manifested right inguinal mass and pain in the mass during menstruation. At 20 years old, she underwent a surgical procedure for right inguinal mass. Postoperative pathology findings demonstrated inguinal endometriosis. Based on the findings of magnetic resonance imaging, a history of inguinal endometriosis, and the occurrence of inguinal pain during menstruation, she was diagnosed as having incarcerated inguinal hernia containing anomalous uterus and endometriosis. A functioning, noncommunicating, rudimentary uterine horn and endometriosis were surgically removed from the hernia sac. Laparoscopy demonstrated intraabdominal unicornuate uterus, but no pelvic endometriosis. CONCLUSION: Functioning, incarcerated hernia uterus inguinale may be associated with müllerian abnormality and concomitant occurrence of inguinal endometriosis.

Isolated adenomyotic cyst associated with severe dysmenorrhea.

A case of a 23‐year‐old, nulliparous female with a very rare isolated adenomyotic cyst inducing severe dysmenorrhea was seen. Transvaginal ultrasonographic tomography and magnetic resonance imaging (MRI) showed a 3 × 3‐cm cystic mass within the left anterior wall of the uterine corpus. The cystic space was filled with hyperintense fluid on T1‐weighted images, which was surrounded by hypointense tissue beside the right uterine corpus on T2‐weighted images. The case was preliminarily diagnosed using MRI as having cavitated rudimentary uterine horn. However, hysterosalpingography excluded the possibility of uterine anomaly. A hemorrhagic adenomyotic cyst measuring 3 cm within the left anterior wall of the uterine corpus was surgically removed. There was no evidence of diffuse adenomyosis uteri. Dysmenorrhea completely disappeared postoperatively.

Severe leg compartment syndrome associated with dorsal lithotomy position during radical hysterectomy

We encountered a female patient with left‐leg compartment syndrome; a devastating complication, probably associated with prolonged dorsal lithotomy position during radical hysterectomy using intermittent pneumatic compression. This patient was intensively treated and fortunately recovered. However, leg compartment syndrome is poorly understood by gynecologists. We must always consider the potential risk of this life‐threatening complication when patients are placed in the dorsal lithotomy position for a prolonged period during extended surgery using intermittent external compression.

Difference in the relative contribution of lean and fat mass components to bone mineral density with generation

Aim:  To investigate whether the relative contribution of body composition (lean and fat mass component) to bone mineral density (BMD) differs depending on generation or menopause.

Successful management of uterine arteriovenous malformation by ligation of feeding artery after unsuccessful uterine artery embolization

Uterine arteriovenous malformation (AVM) is a rare and potentially life‐threatening disease. The present report describes a postmenopausal patient with uterine AVM manifesting recurrent, massive genital bleeding. Uterine artery embolization (UAE) was scheduled before hysterectomy, but UAE was unsuccessful due to the dilated, tortuous internal iliac arteries, and extremely rapid arterial blood flow. Hysterectomy appeared to carry a potential risk of massive blood loss due to multiple dilated vessels around the uterine corpus and cervix. Therefore, six arteries feeding the uterus were surgically ligated. At 10 months after the operation there have been no episodes of atypical genital bleeding.