Effectiveness of prophylactic HPV vaccines against cervical abnormalities and HPV infection in Japan: The J-HERS 2021 multicenter study.

This study investigated the efficacy of the prophylactic human papillomavirus (HPV) vaccine, which was initiated between 2009 and 2013 in Japan. The study involved 1529 eligible women aged 16-39 years who visited 11 outpatient clinics in Japan for various reasons. These patients underwent HPV genotype analysis and a Pap test of cervical cell samples. A total of 299 women (19.6%) had received the prophylactic HPV vaccine (bivalent:quadrivalent vaccine ratio = 2:1). Of the 5062 participants in the Japanese Human Papillomavirus Disease Education and Research Survey (J-HERS 2011), which was conducted in the pre-vaccination era, 3236 eligible participants were included as controls. In this study (J-HERS 2021), the highest rate of HPV vaccination (53%) was observed in patients aged 22-27 years. Vaccinated individuals exhibited a 49% rate of protection against low-grade intraepithelial lesions (LSILs) and atypical squamous cells, not excluding high-grade squamous intraepithelial lesions (ASCH) or worse (LSIL/ASCH+), and a 100% rate of protection against high-grade squamous intraepithelial lesions (HSILs) or worse (HSIL+). Significant reductions in HPV16 (95%) and HPV18 (100%) infections were noted, but no differences were observed in HPV6 and HPV11 infections. The prevalences of HPV51 and HPV59 increased with vaccination, although these changes were not confirmed in the comparative study with J-HERS 2011. Comparing the prevaccination (J-HERS 2011) and postvaccination (J-HERS 2021) periods, 43%, 51%, 88%, and 62% reductions in HPV16, HPV18, HPV16/18, and HPV31/58 infection rates were observed, respectively. Similarly, 62% and 71% reductions in LSIL/ASCH+ and HSIL+ rates were noted, respectively. There were 88% and 87% reductions in LSIL/ASCH+ and HSIL+ rates in 16-21- and 28-33-year-old patients, respectively. Bivalent or quadrivalent vaccines provided 100% protection against high-grade squamous cell lesions (suggestive of CIN2 or CIN3) in young women aged <39 years at 9-12 years after initiation of Japan's first nationwide HPV vaccination program. Cross-protection against HPV31 and HPV58 is likely to occur, although some HPV-type replacements are inconsistent across vaccination regimens. This demonstrates the effectiveness of the HPV vaccine. However, continuous monitoring of cervical cancer and precancer is necessary in younger generations (born 1997-2007), who were rarely vaccinated due to the prolonged suspension of the vaccine recommendations in Japan.

The High-Risk Human Papillomavirus Type Influences the Tissue Microenvironment in Cervical Intraepithelial Neoplasia Grade 2.

High-risk, cancer-causing human papillomavirus (HPV) types are associated with cervical precancer and cancer. A high proportion of high-risk HPV precancer lesions undergo immune-mediated regression. The purpose of this study was to determine if the tissue microenvironment of HPV16 and 18 (HPV16/18) cervical intraepithelial neoplasia grade 2 lesions differed from other high-risk types (HPV 'other'). Consistent with other studies, we found that progression to higher-grade disease was more frequent in HPV16/18 lesions when compared with HPV 'other' lesions. HPV16/18 lesions were significantly more likely to be indoleamine 2,3,-dioxygenase 1 (IDO1)-positive and were associated with reduced CD8 and FoxP3 T cells in the lesion. In the stroma, reduced Tbet- and CD32-positive cells and increased Blimp1-positive cells were significantly associated with HPV16/18 lesions when compared with HPV 'other' types. On analysis of the IDO1-positive tissues, lesional IDO1 was associated with significantly decreased numbers of CD4-, CD8-, and FoxP3-positive cells in the stroma compared with IDO1-negative tissues. These data suggest that IDO1 expression may impair infiltration of CD4, CD8, and FoxP3 cells into the stroma beneath the precancer lesion. Increased expression of IDO1 may contribute to immune avoidance and an increased frequency of disease progression in HPV16- and 18-positive lesions.

Characterisation of the immune microenvironment of cutaneous squamous cell carcinoma in immunosuppression.

Cutaneous squamous cell carcinoma (cSCC) is a common cancer. Systemic immunosuppression with drugs such as Prednisone results in more aggressive disease. We hypothesise that more aggressive disease in immunosuppression is the result of immune changes in the tumor microenvironment. We characterised T cell, phagocytic and antigen presenting cell subsets in cSCC and determined if these infiltrates were altered by immunosuppressive therapy. We found a dominant "CD8 profile" in the centre of cSCC lesions, with CD8 cells correlating with Tbet, FoxP3, OX40 and "M2-like" macrophages, whereas a "Tbet and granulocyte profile" with associated inflammation predominated at the margin of the tumor. Individuals on systemic immunosuppressive therapy had lesions that were comparable in size, stage and number of vessels to immune competent individuals; however, the number of CD11c positive cells in the lesion centre was significantly reduced. We conclude that cSCC lesions are immunologically heterogeneous across the lesion and that systemically immunosuppressed individuals have reduced CD11c positive cells in the centre of the lesion. The role and detailed phenotype of CD11c positive cells in cSCC lesions warrant further investigation.

Determination of human papillomavirus type in archival tissue specimens of invasive cervical cancer using molecular mapping and E6/E7-based polymerase chain reaction.

In our previous study, an L1-based human papillomavirus (HPV) test using liquid-based cytology revealed that some invasive cervical cancers (ICC) exhibited multiple HPV types or harbored no HPV DNA. Here, molecular mapping of formalin-fixed paraffin-embedded cancer tissue specimens from the same patients were conducted to confirm these observations. Among 377 ICC cases, 73 eligible specimens (9 positive for multiple HPV types, 16 negative for HPV, and 48 positive for a single HPV type from the previous study) were reexamined by manual microdissection of cancer lesions, then subjected to HPV genotyping using the uniplex E6/E7 polymerase-chain-reaction method to detect all high-risk and potentially high-risk HPV types. The HPV typing results were confirmed in 52 of 73 cancer cases; among the 21 remaining cases, 15 were discordant and 6 were partially concordant. In total, 8 of 16 (50%) HPV-negative samples became positive; 6 were positive for HPV16 and 2 were positive for HPV67. Moreover, two samples previously positive for HPV6 and HPV53 were negative for HPV. All nine cancers with multiple HPV types were found to harbor only a single HPV type. In total, 63 cancer tissues exhibited a single HPV type. HPV16 and HPV18 were detected in squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Alpha-5 (HPV82), -6 (HPV56), and -9 (HPV31/52/67) HPV types were detected in SCC, whereas Alpha-7 (HPV59/68) types were detected in ADC and adenosquamous carcinoma (ADSCC). These findings suggested that the different HPV types induced different histological cancers. Furthermore, all SCCs and 10 of 11 usual-type ADCs were positive for high-risk HPV types, supporting the use of HPV screening for the detection of these cancers and associated premalignant lesions. HPV16 is likely to remain undetected in some cervical cancer tissues because of low viral-copy-numbers. Putative high-risk HPV types (e.g., HPV67 and HPV82) might be high risk in Japan.

Blimp-1 is a prognostic indicator for progression of cervical intraepithelial neoplasia grade 2.

BACKGROUND: Progression of cervical intraepithelial neoplasia (CIN) to higher grade disease is associated with persistent human papillomavirus (HPV) infection and an absence of immune-mediated regression. However, the immune microenvironment that distinguishes progression from persistent or regressing lesions has not been well defined. METHODS: A total of 69 patients under the age of 25 with high-risk HPV-positive cytology and biopsy-confirmed p16-positive CIN2 were included in the study. Biopsies were stained using 20 antibodies to a range of immune markers. Based on a 2-year follow-up, samples were analysed in "progressor" (CIN3 +) or "persister/regressor" (CIN1, 2 or normal) groups. RESULTS: Progression was most strongly associated with Blimp-1 positive cell staining in the lesion (P = 0.0019) and with low numbers of infiltrating CD4 cells in the dermal region beneath the lesion (P = 0.0022). The presence of CD4, CD8 and T bet-positive cells in the dermal region most strongly correlated with CD11c cells in the persister/regressor but not the progressor group. CONCLUSION: High numbers of Blimp-1 + cells in CIN2 lesions may predict progression to more severe disease. Measurement of Blimp-1 may have diagnostic utility for the determination of the need to treat women with cervical pre-cancer. HIGHLIGHTS: CIN2 progression is associated with high numbers of Blimp-1 positive cells in the lesion. Detection of Blimp-1 in the lesion may have utility as a prognostic test to inform the need to treat CIN2.

Front crawl body roll characteristics in a Paralympic medallist and national level swimmers with unilateral arm amputation.

The purpose of this study was to establish the asymmetry and body wave characteristics related to shoulder, hip, knee, and ankle roll in unilateral arm amputee swimmers. Three unilateral arm amputee swimmers, including one Paralympic medallist (swimmer A), volunteered in this study. They conducted two 10-15 s front crawl tests with sub-maximum and maximum speeds in a flume. Shoulder, hip, knee, and ankle roll amplitude and progression of a torsional body wave was quantified using a motion capture system and a Fourier analysis. Swimmer A showed 50% higher stroke frequency than the other swimmers. Swimmers achieved larger shoulder roll amplitude towards the affected than the unaffected side by 19-89%. Swimmer A showed body wave velocity slowing down when it travelled caudally, while national level swimmers presented increasing wave velocity, suggesting that swimmer A had a less effective kicking than the other swimmers. In conclusion, the technique of the unilateral arm amputee swimmers was characterised by a large shoulder roll angle towards the affected side. The Paralympic medallist had larger shoulder roll asymmetry and less effective kicking than the other swimmers and yet achieved higher swimming speed because of his high stroke frequency.

HPV Genotyping by Molecular Mapping of Tissue Samples in Vaginal Squamous Intraepithelial Neoplasia (VaIN) and Vaginal Squamous Cell Carcinoma (VaSCC).

HPV genotypes were determined in 63 vaginal squamous intraepithelial neoplasia (VaIN) and 7 vaginal squamous cell carcinomas (VaSCC). Of these, 37 cases had VaIN alone, and 26 cases had both VaIN and cervical intraepithelial neoplasia (CIN) or condyloma. HPV typing was performed in scraped cells by Genosearch-31 (GS-31) and in the archived tissues by uniplex E6/E7 PCR. In a total of 49 VaIN1, 17 VaIN2/3, and 7 VaSCC tissues, the prevalence of HPV was 91.2% in VaIN (VaIN1: 87.8%, VaIN2/3: 100%) and 85.7% in VaSCC. Comparing HPV results in scraped cell and tissue, 46.2% of high-risk (HR) types and 68.1% of any HPV types that had been identified in cell samples were not present in corresponding tissues. HPV types in VaIN and CIN lesions differed in 92.3% (24/26) of cases with multiple lesions. These results suggest that there are many preclinical HPV infections in the vagina or the cervix, and VaIN and CIN are independently developed. The manual microdissection procedure of tissue revealed one HPV type in one lesion. Seventeen HPV types, including high-risk (HR), possible high-risk (pHR), and low-risk (LR), were identified in 43 VaIN1 lesions. In higher grade lesions, six HR (HPV16, 18, 51, 52, 56, 58), one pHR (HPV66), and one LR (HPV42) HPV types were identified in 17 VaIN2/3, and six HPV types, including HPV16, 45, 58, and 68 (HR), and HPV53 and 67 (pHR), were detected in each case of VaSCC. The vagina appears to be the reservoir for any mucosal HPV type, and HR- or pHR-HPV types are causative agents for vaginal malignancies.

Differences in Mechanical Parameters of Keyboard Switches Modulate Motor Preparation: A Wearable EEG Study.

The mechanical parameters of keyboard switches affect the psychological sense of pressing. The effects of different mechanical parameters on psychological sense have been quantified using questionnaires, but these subjective evaluations are unable to fully clarify the modulation of information processing in the brain due to these differences. This study aimed to elucidate the ability of electroencephalography (EEG) measurements to detect the modulation of subconscious information processing according to mechanical parameter values. To this end, we prepared five mechanical switches with linearly increasing values of pretravel (PT: the distance from the free position until the operating position). We hypothesized that the differences in PTs would subconsciously affect the motor preparation prior to pressing switches because switches with PTs that deviated from those commonly used were predicted to increase the users' attention level when pressing. Differences in motor preparation were quantified using the mean amplitudes of the late contingent negative variation (CNV). We recorded EEGs of 25 gamers during a reaction task for fast switch pressing after a response cue preceded by a pre-cue for response preparation; we also measured the reaction time feedback on each switch pressing trial. Participants performed five sessions (60 trials per session) in total. For the analysis, trials were divided into first (session 1, 2, and 3) and second half sessions (session 4 and 5). In the latter session, CNV amplitudes were significantly higher for the switch with the highest PT than for that with a medium PT, which is closest to that commonly used in commercial mechanical switches. On the other hand, the questionnaire did not detect any significant differences between PTs in their subjective rankings of the psychological effects of switch pressing. These results suggest that differences in PTs modulate motor preparation to press switches, and that EEG measurements may provide a novel objective evaluation of the mechanical parameters of keyboard switches.

Association between mean platelet volume in the pathogenesis of type 2 diabetes mellitus and diabetic macrovascular complications in Japanese patients.

AIMS/INTRODUCTION: Mean platelet volume (MPV) is a widely used biological marker of platelet function and activity. Increased MPV is associated with accelerated thrombopoiesis and an elevated risk of cardiovascular disease. However, it is not known whether higher MPV is related to the pathogenesis of type 2 diabetes and diabetic macrovascular complications in Japanese patients. Therefore, we analyzed MPV and its correlation with atherosclerosis in Japanese patients with type 2 diabetes and those who had prediabetes. MATERIALS AND METHODS: We divided the patients into three groups: normoglycemic patients (n = 56), prediabetes patients (n = 44) and type 2 diabetes patients group, (n = 115). We measured platelet parameters and evaluated arterial stiffness in the three groups. RESULTS: Significantly higher MPV was found in the type 2 diabetes mellitus and prediabetes patients compared with normoglycemic patients. MPV was significantly correlated with fasting blood glucose and glycated hemoglobin levels. Multiple linear regression analysis showed that MPV was positively correlated with HbA1c, even after adjustment for confounding factors. In the evaluation of arterial stiffness by measuring the cardio-ankle vascular index and maximum intima-media thickness, MPV showed a positive correlation with these parameters. CONCLUSIONS: These findings suggest that MPV was significantly increased in the early stage of type 2 diabetes. We showed positive correlations between MPV and HbA1c levels, and between MPV and arterial stiffness in Japanese patients with type 2 diabetes.

The prevalence of VAIN, CIN, and related HPV genotypes in Japanese women with abnormal cytology.

Vaginal intraepithelial neoplasia (VAIN) is often found by chance. We investigated the prevalence of VAIN and related human papillomavirus (HPV) types in comparison with cervical intraepithelial neoplasia (CIN). This study enrolled 648 women who were referred to the outpatient clinic of Kanazawa Medical University Hospital for abnormal cytology from January 2009 to January 2019. HPV genotypes were determined using Genosearch-31 + 4, which can detect 35 different HPV types. Colposcopy was performed at the first visit by an experienced gynecological oncologist. Among 611 subjects with squamous cell lesions, 107 (17.5%) VAIN cases were identified, and 67 (11.0%) women had both VAIN and CIN. Ultimately, 72 VAIN1, 15 VAIN2/3, 203 CIN1, 249 CIN2/3, 32 cervical squamous cell carcinomas (SCC), and one vaginal SCC (Vag-SCC) were identified. The prevalences of VAIN1, VAIN2/3, and Vag-SCC were 35.5%, 6.0%, and 3.1% of equivalent cervical lesions, respectively. The VAIN patients were older than the CIN patients (P = .002). About half of the VAIN cases were diagnosed during the follow-up. Multiple HPV infections were found in 42.9% of the VAIN and CIN patients. HPV52, 16, 51, 53, and 56 were the most common types in VAIN, whereas HPV16, 52, 58, 51, and 31 predominated in CIN. HPV18 was rare in VAIN, HPV58 was more common in CIN than in VAIN, and HPV53 and HPV73 were more common in VAIN. In conclusion, VAIN1 was identified more frequently than we expected. Various HPV types were identified in the vagina, which is likely a reservoir for HPV.

Rapid identification of sound direction in blind footballers.

Earlier studies have demonstrated that blind footballers are more accurate in identifying sound direction with less front-back confusion than sighted and blind non-football playing individuals. However, it is unknown whether blind footballers are faster than sighted footballers and nonathletes in identifying sound direction using auditory cues. Here, the present study aimed to investigate the auditory reaction times (RTs) and response accuracy of blind footballers during auditory RT tasks, including the identification of sound direction. Participants executed goal-directed stepping towards the loudspeaker as quickly and accurately as possible after identifying the sound direction. Simple, two-choice, and four-choice auditory RT tasks were completed. The results revealed that blind footballers had shorter RTs than sighted footballers in the choice RT tasks, but not in the simple RT task. These findings suggest that blind footballers are faster in identifying sound direction based on auditory cues, which is an essential perceptual-cognitive skill specific to blind football.

Age-related differences in cognitive function for interlimb coordination during split-belt walking: a pilot study.

While walking is considered a task demanding cognitive functions rather than an automatic motor task, it is still unclear whether cognitive tasks influence interlimb coordination during walking. The present study revealed that the elderly require cognitive function to control temporal interlimb coordination under difficult walking conditions. Risk of falls is thus likely to be increased in the elderly when performing attention-demanding tasks while walking.

Use of a cane for recovery from backward balance loss during treadmill walking.

PURPOSE: To study whether a cane improved balance recovery after perturbation during walking. METHOD: This study was a crossover comparison comparing the effect of walking with and without a cane for balance recovery after perturbation during treadmill walking. Five normal young volunteers participated. The velocity and acceleration of a marker sited on the seventh cerebral vertebra (C7) and vertical hand motion were measured by a motion analysis system. RESULT: When using a cane, C7 backward velocity increased by approximately 15% (413 SD 95 mm/s with cane vs. 358 SD 88 mm/s without). In addition, C7 backward acceleration increased by approximately 23% (3.2 SD 0.7 m/s(2) with cane vs. 2.6 SD 0.8 m/s(2) without) and the vertical motion of the right hand decreased (187 SD 98 mm with cane vs. 372 SD 260 mm without). Additionally, no subject was able to use a cane to broaden their base of support. CONCLUSIONS: The ability to limit trunk extension is crucial for preventing falls. Therefore, using a cane jeopardizes recovery from backward balance loss. The results encourage further research on the risk of a cane on balance recovery for the elderly population and habitual cane users.

Anticipatory postural adjustments contribute to age-related changes in compensatory steps associated with unilateral perturbations.

Compensatory steps are essential for preventing falls following perturbations. This study aimed to explore age-related changes in compensatory steps to unilateral perturbations, specifically in terms of whether anticipatory postural adjustments (APAs) play a role in stabilizing lateral balance. Five young and five elderly male adults participated. The split-belt treadmill was used to provide bi- and unilateral perturbations, as forward or backward transitions, applied 10 times in random order. Backward steps evoked by unilateral forward perturbations were evaluated. We measured temporal characteristics, mediolateral (ML) center of mass (COM) motion, and ML step length of compensatory steps. Compensatory steps to unexpected perturbations showed delayed onset of foot-off (FO) and expanded lateral swing length in elderly compared to young subjects. Differences in COM motions and step width arose related to APAs. Elderly subjects showing APAs exhibited no significant differences in ML COM, ML COM velocity, or ML swing length compared to young subjects. However, elderly subjects without APAs showed significant changes toward instability in these parameters. The fact that APAs play a notable role, particularly in the elderly, in stability offers a new insight into preventing falls. However, APAs occurred in 29% of the steps of young and 35% of the steps of elderly subjects. If the occurrence of APAs in elderly people in response to compensatory steps was more frequent, fall risk would be reduced. Further studies, particularly into APA frequency, might contribute to improved intervention to prevent falls.

[Assistance provided with home nursing care for a terminal cancer patient].

A visiting nursing service was provided for a 90-year-old male patient with terminal stage of pancreatic cancer whose prognosis was to live for two to three months. We provided nursing service not only for the patient's pain control but also for the member of the family by giving specific nursing tips as well as mental support. After the patient passed away, the eldest daughter was quoted saying "we could do everything we wanted to from home nursing care." It appeared that she was totally satisfied with our nursing service. We concluded the following caregiver roles based on this clinical example: 1) Try to alleviate a terminal patient's pain as much as possible so that the patient and the family will be at ease. 2) Arrange the care giver's anxiety individually. 3) Guide the care giver a specific know-how that can be accomplished and let the patient and the care giver choose which one they want. 4) Teach the process of the withholding and with drawing of life and try to consolidate the purpose of nursing intentions among the care givers. 5) Respect the patient and caregiver and make the best out of the situation by being flexible.

Angiogenic factors in normal endometrium and endometrial adenocarcinoma.

In the endometrium, angiogenesis plays important roles not only in tumor growth but also in the menstrual cycle. The purpose of the present paper was to investigate immunohistochemically the correlation between angiogenic factor expression and angiogenic score in normal and neoplastic endometrium. Immunohistochemical staining for vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1, Ang2, Tie2, CD34 and CD105 was performed on formalin-fixed and paraffin-embedded tissues from 31 normal endometrium and 85 endometrial adenocarcinoma. VEGF, Ang1, Ang2 and Tie2 expression was localized in the cytoplasm of glandular and tumor cells. The levels of each angiogenic factor were different in the phases of the menstrual cycle and each layer of normal endometrium. In general, VEGF and Tie2 expression was higher in adenocarcinoma than in normal epithelial cells. Conversely, Ang1 and Ang2 expression was higher in normal epithelium than in adenocarcinoma. The angiogenic score (CD105/CD34) tended to be higher in the adenocarcinoma than in the normal epithelium. It is suggested that the angiogenic pathway and the role of these factors seem to differ between normal tissue and carcinoma of the endometrium.

[A visiting nursing support for a patient having a stoma apparatus who has been taking an outpatient cancer chemotherapy].

We provided a visiting nursing support for a 40-year something patient having a stoma apparatus who has been taking a periodical outpatient cancer chemotherapy. Due to fever, nausea, vomiting and a loss of appetite caused by the chemotherapy, we decided to make an observation of the patient's daily life and conducted how to cope with the side effects in our support for the patient. We also provided daily life essentials such as a help supporting the patient how to replace a stoma apparatus and assistance to take bath. In a case of stoma protrusion caused by the progress of the disease, we aligned treatment procedures by consulting with a certified nurse specialized in dermatology and excrete care. One of the roles for a visiting nurse is to assess the patient's drug side effects as well as how the side effects have been affecting the daily life of patient. Furthermore, it is necessary to give an encouragement for the patient to get anxieties out and to give a specific life style coaching on the individual bases. It appears to be useful that patient's QOL will be enhanced by sharing information with the home care life of patient and to work with the patient.

Urinary excretion of liver fatty acid-binding protein in health-check participants.

BACKGROUND: Messenger RNA of liver fatty acid-binding protein (L-FABP) is expressed in proximal tubules of the kidney, and a certain amount is excreted into urine. We analyzed factors relating to the urinary L-FABP excretion in health-check participants. METHODS: We measured L-FABP in the first morning urine by ELISA in 715 men and 193 women 30-79 years of age who entered a 2-day hospitalized health checkup program. In addition to the routine physical examination and laboratory tests, plasma high-sensitivity C-reactive protein (HSCRP) was assayed. RESULTS: In 150 healthy subjects, urinary L-FABP averaged 3.6 +/- 0.2 microg/g creatinine, whereas the values were significantly increased in patients with hypertension (5.2 +/- 0.4, P = 0.010), diabetes mellitus (5.5 +/- 0.5, P < 0.001), and chronic hepatitis (5.8 +/- 1.0, P = 0.022). Urinary L-FABP excretion was significantly greater in women than in men when the value was related to creatinine. In regression analysis in men, urinary L-FABP was positively correlated with fasting plasma glucose (r = 0.103, P = 0.033) and plasma HSCRP (r = 0.135, P = 0.006). CONCLUSIONS: It is suggested that renal production and urinary excretion of L-FABP are increased in situations in which arteriosclerosis is promoted, such as hypertension, diabetes mellitus, and cardiovascular inflammation.

Significance of progesterone receptor-A and -B expressions in endometrial adenocarcinoma.

The progesterone receptor (PR) has two isoforms, A and B, among which PR-B is mainly involved in regulating proliferation of the uterine endometrium. In this study, immunohistochemical analysis was carried out to investigate the correlation of PR-A and -B expressions with cell cycle-regulatory proteins and clinicopathological parameters in endometrial adenocarcinoma. One hundred and forty-one endometrioid adenocarcinomas [76 with well-differentiated (G1), 35 with moderately differentiated (G2) and 30 with poorly differentiated (G3)] were used. Specimens of formalin-fixed and paraffin-embedded tissue were immunohistochemically stained using the high polymer method (HISTOFINE, NICHIREI). The percentage of positive nuclei of tumor cells observed in three high power fields was expressed as a labeling index (LI). PR-B expression significantly occurred more frequently in G1. It was inversely correlated with p53 gene mutation and p53 over expression, and also with clinicopathological variables, including myometrial and lymph-vascular space invasion and the FIGO stage. Patients with negative PR-B had a poorer prognosis than positive cases. PR-A expression was also significantly higher in G1 and was inversely correlated with Ki-67 expression and myometrial invasion, but not with prognosis. PR-A and -B expressions were significantly correlated with biologically malignant potential. Especially, PR-B expression is useful as a prognostic indicator of endometrial adenocarcinoma.

Relations of plasma high-sensitivity C-reactive protein to traditional cardiovascular risk factors.

Variations of circulating C-reactive protein (CRP) levels are supposed to reflect chronic inflammatory process of the cardiovascular system. In particular, it has been reported that high-sensitivity CRP (hsCRP) is a promising marker of coronary heart disease. In the present study, we assessed the relationship between hsCRP and classic cardiovascular risk factors, such as age, blood pressure, smoking habit and serum lipids. Plasma hsCRP was measured by ELISA in 908 subjects, aged 30-79 years, who entered our health-check program. Plasma hsCRP level was 0.54+/-0.02 mg/l in 566 subjects without any disease currently treated. The level was significantly higher in patients treated for hypertension (0.74+/-0.06 mg/l, P=0.002), diabetes mellitus (0.77+/-0.09 mg/l, P=0.016) or coronary artery disease (0.99+/-0.16 mg/l, P=0.008) than in subjects without diseases. In a simple regression analyses of the 566 subjects without diseases, plasma hsCRP positively correlated with male gender, smoking, body mass index, systolic blood pressure, white blood cell count, blood hemoglobin, fasting blood glucose, serum gamma-GTP, uric acid and triglycerides, and inversely correlated with serum albumin and HDL-cholesterol. In multiple regression analysis, white blood cell count (r=0.276, P<0.001), body mass index (r=0.246, P<0.001), age (r=0.122, P=0.001) and smoking (r=0.112, P=0.009) showed independent correlations with plasma hsCRP. It is suggested that variation of circulating hsCRP, even within normal range, is involved in the interrelation of cardiovascular risk factors, such as age, smoking, obesity, high blood pressure and dyslipidemia, which are supposed to promote atherosclerosis and ultimately provoke cardiovascular diseases, such as coronary artery disease.