[Clinicopathological and survival analysis of 34 cases of uterine clear cell carcinoma].

Objective: To analyze the clinicopathological features and prognostic factors of patients with uterine clear cell carcinoma (UCCC). Methods: UCCC patients who underwent surgery and complete follow-up at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 1, 2004 and December 31, 2014 were retrospectively reviewed. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results: The study included 34 patients. Only 18 patients (52.9%) were diagnosed with UCCC preoperatively and 8 patients (23.5%) underwent UCCC standard comprehensive staging surgery. Among the 34 patients, stage ⅠA was 17 cases (50.0%), stage ⅠB was 1 case (2.9%), stage Ⅱ was 4 cases (11.8%), stage ⅢA was 2 cases (5.9%), stage ⅢB was 1 case (2.9%), stage ⅢC1 was 5 cases (14.7%) and stage ⅣB was 4 cases (11.8%). The median follow-up period was 72 months, 5-years disease-free survival (DFS) rate and overall survival (OS) rates for all patients were 79.1% and 81.3%, respectively. Univariate analysis result showed that preoperative CA125 level, range of lymphadenectomy, tumor stage and peritoneal cytology were significantly associated with DFS (P<0.05). Preoperative CA125 level, range of lymphadenectomy, tumor stage, peritoneal cytology and lymph vascular space invasion were significantly associated with OS (P<0.05). Multivariate analysis result showed that peritoneal cytology was the only independent prognostic factor for DFS, the relapse risk of peritoneal cytology positive patients was 11.47 folds higher than that of the negative patients (P=0.009). Tumor stage was the only independent prognostic factor for OS, the death risk of ⅣB stage patients was 25.29 folds higher than that of theⅠA stage (P=0.009). Conclusions: The preoperative pathological diagnosis of UCCC is difficult, which results in incomplete surgical staging. Peritoneal cytology and tumor stage are independent prognostic factors for DFS and OS of UCCC patients, which deserve much more attention in clinical practice.

[Diagnosis, treatment and prognosis of uterine serous carcinoma].

Objective: To investigate the diagnosis, treatment and prognosis of uterine serous carcinoma (USC), and further analyze the prognostic factors. Methods: USC patients who underwent surgery with complete follow-up at Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences between January 1, 2004 and December 31, 2014 were retrospectively reviewed. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Results: (1) Diagnosis and treatment: the study included 71 USC patients. Only 32 patients (45%, 32/71) were diagnosed preoperatively with USC, and 25 cases of them (35%, 25/71) underwent USC standard comprehensive staging surgery. Of the 25 patients, 10 cases (40%, 10/25) had up-staged after operation. (2) Prognosis: the 5-year disease free survival (DFS) rate and overall survival (OS) rate for all patients were 76.5% and 80.6%, respectively. (3) The results of prognostic factors analysis: univariate analysis on age, range of lymphadenectomy, peritoneal cytology, the depth of myometrial invasion, adnexal and (or) serosa involvement and omentum metastasis were significantly associated with 5-year DFS rate (all P<0.05); range of lymphadenectomy, range of surgical staging, peritoneal cytology, adnexal and (or) serosa involvement and postoperative adjuvant treatment were significantly associated with 5-year OS rate (all P<0.05). Multivariate analysis on range of surgical staging (HR=5.18, 95%CI: 1.04-25.70, P=0.044) and adnexal and (or) serosa involvement (HR=8.41, 95%CI: 2.28-31.05, P=0.001) were independent prognostic factors for 5-year DFS rate; range of lymphadenectomy [no lymphadenectomy vs pelvic lymphadenectomy (PLN)+para-aortic lymphadenectomy (PALN), HR=27.76, 95%CI: 1.76-437.78, P=0.018;PLN vs PLN+PALN, HR=5.98, 95%CI: 1.11-32.27, P=0.038] and peritoneal cytology (HR=5.47, 95%CI: 1.18-25.39, P=0.030) were independent prognostic factors for 5-year OS rate. Conclusions: The preoperative pathological diagnosis of USC is difficult, resulting in incomplete surgical staging and inaccurate staging. Range of surgical staging, adnexal and (or) serosa involvement, peritoneal cytology and range of lymphadenectomy are independent prognostic factors, which deserve much attention in clinical practice.

[Analysis of effects and postoperative clinicopathological prognosis factors of neoadjuvant chemotherapy in patients with stage â b2 and â ¡a2 squamous cell carcinoma of the cervix].

Objective: To explore the effects and postoperative prognostic factors in cervical cancer patients received neoadjuvant chemotherapy combined with surgery and post-operative adjuvant therapy. Methods: A total of 177 patients with cervical cancer at International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ b2, Ⅱ a2 who underwent neoadjuvant chemotherapy (NACT) followed by surgery with and without adjuvant therapy in Cancer Hospital, Chinese Academy of Medical Sciences were included. Univariate and multivariate analyses of 5-year overall survival (OS) rate and 5-year disease-free survival (DFS) rate were performed. Results: Of 177 patients, 133 (75.1%) had stage Ⅰb2 and 44 (24.9%) had Ⅱa2 cancers. After NACT, overall response rate was 63.3% (112/177) including 12 cases of complete response (CR), 100 of partial response (PR) and no progressive disease (PD) case. At a median follow-up of 59.2 months, the 5-year DFS rate was 73.6% and the 5-year OS rate was 86.8%. Univariate analysis revealed that lymph node metastasis, deep stromal invasion and tumor size after NACT significantly affected 5-year DFS rate (P<0.05). Lymph node metastasis, deep stromal invasion and tumor size after NACT significantly affected 5-year OS rate (P<0.05). The multivariate analysis showed that, stromal invasion (outer 1/3 or outer 1/2) was independent risk factor of 5-year DFS rate (P<0.05), and 5-year OS rate was significantly affected by tumor size >3 cm after NACT (P<0.05). Conclusions: The effect of NACT in Ⅰ b2, Ⅱ a2 squamous carcinoma of the uterined cervix is confirmed. The independent risk factor for 5-year DFS rate in patients received NACT and hysterectomy is deep stromal invasion of the cervix. The presence of tumor size >3 cm after NACT adversely affect 5-year OS rate.

[Recurrence pattern and influencing factors of intensity-modulated radiotherapy for cervical cancer].

With the rapid development of precise radiotherapy technology, the use of intensity-modulated radiation therapy (IMRT) in gynecological malignant tumor has been gradually increased. IMRT could result in a good local control rate as well as superior clinical outcome in patients with cervical cancer after radical radiotherapy. The recurrence pattern of radiotherapy includes in-field recurrence, out-of-field and combined failure. The recurrence pattern of radical IMRT for cervical cancer is mainly out-of-field recurrence. Out-of-field recurrence may be related to inadequate imaging evaluation before treatment. In-field recurrence may be related to insufficient radiation dose in target area and differences of tumor sensitivity.

[Analysis of prognostic factors and therapeutic patterns of recurrent stage â b-â ¡a cervical squamous carcinoma treated with radical hysterectomy].

Objective: To analyze the prognosis and appropriate treatment modalities of the patients with recurrence of early stage (Ⅰb-Ⅱa) cervical squamous cancer primarily treated with radical hysterectomy. Methods: This retrospective study included patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰb and Ⅱa recurrent cervical squamous cancer who underwent radical hysterectomy primarily from January 2007 to July 2015. Kaplan-Meier method and Cox regression analysis were performed to analyze related prognostic factors of overall survival and progression-free survival, which included age, postoperative therapy, the site of recurrence, therapy-free interval (TFI) and treatment modality. The patients who were treated with palliative chemotherapy after recurrence were selected as a subgroup. The responses of palliative chemotherapy were evaluated and analyzed among different factors, included TFI, the site of recurrence and chemotherapy regime. Results: Of the 2 071 patients, 116 relapsed Ⅰb-Ⅱa cervical squamous cancer were included in the study with the average age of (45.6±7.2) years old. 3-year progression-free survival rate and 3-year overall survival rate after recurrence were 30.2% and 42.2%, respectively. Univariate analysis implied that postoperative radiotherapy, recurrence site, TFI and treatment modality were associated with progression-free survival (P<0.05), while postoperative radiotherapy, TFI and treatment modality with overall survival (P<0.05). Multivariate analysis showed that TFI and treatment modality were independent prognostic factors for progression-free survival (P<0.05), while postoperative radiotherapy at initial treatment, TFI and treatment modality were independent prognostic variables for overall survival (P<0.05). In the analysis of treatment modality, 3-year progression-free survival rate and 3-year overall survival rate of 47 patients who were treated with definitive local therapy were significantly higher than that of 69 patients who were treated with palliative chemotherapy (P<0.01). In the subgroup analysis of palliative chemotherapy, 15 patients achieved complete response (21.7%) and 16 displayed partial response (23.2%). The overall response rate (ORR) was 44.9%. TFI (P<0.01) and chemotherapy regime (P<0.05) were significant factors associated with ORR. The ORR of TFI ≥12 months was significantly higher than that of TFI <12 months. Besides, the ORR of paclitaxel plus platinum chemotherapy was prominently higher than that of other regimens, while there was no significant difference between the ORR of paclitaxel plus cisplatin and other platinum (P=0.408). Conclusions: For recurrent stageⅠb-Ⅱa cervical squamous carcinoma treated with radical hysterectomy, use of definitive local therapy for suitable patients is advised to achieve better prognosis. In terms of palliative chemotherapy, longer TFI may mean better ORR and the combination of paclitaxel plus platinum is preferred.

[Prevalence and attribution of high-risk HPV in different histological types of cervical cancer].

Objective: To investigate the prevalence of high-risk HPV subtypes in different pathological types of cervical cancer, and analyze the attribution of carcinogenic HPV subtypes in different pathological types. Methods: A total of 1 541 patients with cervical cancer were treated between February 2009 and October 2016 in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. The median age at diagnosis was 49 years (ranged 20-82 years old). The numbers of patients with cervical cancer from North China, Northeast China, East China, Central China and other regions (including Northwest, Southwest and South China) were 961, 244, 175, 87 and 74 cases, respectively. Pathological types: 1 337 cases of squamous cell carcinoma (SCC), 87 usual adenocarcinoma (ADC), 23 adenosquamous carcinoma (ASC), 20 mucinous carcinoma (MC), 19 clear cell carcinoma (CCC), 12 endometrioid carcinoma (EC), 25 neuroendocrine carcinoma (NEC), 9 serous carcinoma (SC), 5 villous adenocarcinoma (VADC) and 4 minimal deviation adenocarcinoma (MDAC). The prevalence of high-risk HPV in different regions, age groups at diagnosis and pathological types in cervical cancer were analyzed. The attribution of 13 high-risk HPV subtypes in different pathological types of cervical cancer based on proportional attribution method, and the attribution of high-risk HPV subtypes prevented by 9-valent HPV vaccine in SCC and ADC were calculated. Results: (1) The prevalence of high-risk HPV in 1 541 patients with cervical cancer was 86.6% (1 335/1 541). The multiple high-risk HPV infection rate in patients with SCC ≥60 years old (23.0%, 37/161) was significantly higher than those in patients aged 45-59 years old and ≤44 years old [11.4% (85/747) vs 11.7% (50/429), P<0.01], and the high-risk HPV infection rates of patients with cervical cancer in North China, Northeast China, East China, Central China and other regions were respectively 86.8% (834/961), 87.7% (214/244), 83.4% (146/175), 83.9% (73/87) and 91.9% (68/74). SCC (86.8%, 1 337/1 541) and ADC (5.6%, 87/1 541) were the most common pathological types in cervical cancer. The high-risk HPV prevalence of SCC, ADC, ASC, MC, NEC and VADC were 90.1% (1 205/1 337), 74.7% (65/87), 87.0% (20/23), 65.0% (13/20), 72.0% (18/25) and 5/5 respectively. The high-risk HPV infection rates of SC, EC, CCC and MDAC were 4/9, 3/12, 2/19 and 0/4 respectively. (2) According to proportional attribution, HPV 16 (69.5%), HPV 18 (5.6%), HPV 58 (2.2%), HPV 31 (1.9%), HPV 52 (1.4%) and HPV 33 (1.3%) were the six common high-risk HPV subtypes in SCC. While, HPV 18 (44.1%), HPV 16 (20.5%), HPV 52 (2.3%), HPV 58 (1.2%) and HPV 51 (1.2%) were the main carcinogenic subtypes in ADC. The main carcinogenic high-risk HPV subtypes of ASC, NEC and MC were HPV 18 and HPV 16. The total attribution of HPV 16, 18, 31, 33, 45, 52 and 58 prevented by 9-valent HPV vaccine in SCC and ADC were 82.6% and 68.1% respectively; the attribution of HPV 45 in SCC and ADC were only 0.8% and 0. Conclusions: SCC and ADC are the main pathological types in cervical cancer. SCC, ADC, ASC, MC, NEC and VADC are closely related to high-risk HPV infection. HPV 16 is the main carcinogenic genotypes of SCC. HPV 18 maybe play an important role in the pathogenesis of ADC.

Bi3+ sensitized Y2WO6:Ln3+ (Ln=Dy, Eu, and Sm) phosphors for solar spectral conversion.

The phosphors of Y2WO6:Bi3+, Ln3+ (Ln=Dy, Eu and Sm) were synthesized by solid-state reaction in this study. The crystal structure, photoluminescence properties and energy transfer mechanism were investigated. By introducing Bi3+ ions, the excitation band of the phosphors was broadened to be 250-380 nm, which could be absorbed by the dye-sensitized solar cells (DSSCs). The overlap between excitation of W-O groups/Bi3+ and the emission of Ln3+ (Dy, Eu, and Sm) indicated that the probability of energy transfer from W-O groups and Bi3+ to Ln3+. The energy transfer efficiency from Bi3+ to Ln3+ (Ln=Dy, Eu and Sm) are calculated to be 16%, 20% and 58%. This work suggested that Y2WO6:Bi3+, Ln3+ (Ln=Dy, Eu and Sm) might be a promising ultraviolet-absorbing luminescent converter to enhance the photoelectrical conversion efficiency of dye-sensitized solar cells (DSSCs).

The luminescence properties of Bi(3+) sensitized Gd2MoO6:RE(3+) (RE=Eu or Sm) phosphors for solar spectral conversion.

Gd2MoO6:RE(3+) (RE=Eu or Sm) and Gd2MoO6:Bi(3+), RE(3+) (RE=Eu or Sm) phosphors have been synthesized by combustion method. The samples are characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), photoluminescence excitation (PLE) and photoluminescence (PL) spectra. By introducing Bi(3+) ions into Gd2MoO6:RE(3+) (RE=Eu or Sm) phosphors, the excitation bands of Eu(3+) and Sm(3+) ions are broadened and shifted to short wavelength, meanwhile, the emission intensity are enhanced obviously. The energy transfer from Bi(3+) to the activators of Eu(3+) or Sm(3+) is observed and discussed. In addition, the process of ultraviolet light (250-400nm) converted into visible light can be achieved by using Gd2MoO6:Bi(3+), RE(3+) (RE=Eu or Sm) phosphor. These phosphors can be a promising ultraviolet-absorbing luminescent converter to enhance the photoelectrical conversion efficiency of dye-sensitized solar cells (DSSCs).

United States (US) multi-center study to assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III).

STUDY DESIGN: Multi-center, prospective, cohort study. OBJECTIVES: To assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III) in measuring functional ability in persons with spinal cord injury (SCI). SETTING: Inpatient rehabilitation hospitals in the United States (US). METHODS: Functional ability was measured with the SCIM III during the first week of admittance into inpatient acute rehabilitation and within one week of discharge from the same rehabilitation program. Motor and sensory neurologic impairment was measured with the American Spinal Injury Association Impairment Scale. The Functional Independence Measure (FIM), the default functional measure currently used in most US hospitals, was used as a comparison standard for the SCIM III. Statistical analyses were used to test the validity and reliability of the SCIM III. RESULTS: Total agreement between raters was above 70% on most SCIM III tasks and all κ-coefficients were statistically significant (P<0.001). The coefficients of Pearson correlation between the paired raters were above 0.81 and intraclass correlation coefficients were above 0.81. Cronbach's-α was above 0.7, with the exception of the respiration task. The coefficient of Pearson correlation between the FIM and SCIM III was 0.8 (P<0.001). For the respiration and sphincter management subscale, the SCIM III was more responsive to change, than the FIM (P<0.0001). CONCLUSION: Overall, the SCIM III is a reliable and valid measure of functional change in SCI. However, improved scoring instructions and a few modifications to the scoring categories may reduce variability between raters and enhance clinical utility.

The prognostic values of soft tissue sonography for adult cellulitis without pus or abscess formation.

Abstract The current practice for cellulitis in diagnosis and treatment is mainly based on subjective clinical judgement without validated objective guidance. For patients with non-purulent cellulitis needing intravenous antibiotic treatment in hospital, we found soft tissue sonography performed around 4 days after initiation of antibiotics might have prognostic values. The patients with soft tissue sonographic pattern of subcutaneous thickening alone had shorter duration of antibiotic treatment and higher rate of early treatment response to antibiotics than those with the pattern of cobblestone appearance. Larger-scale research may be warranted to validate the prognostic roles of sonography in cellulitis management.

Association between human papillomavirus DNA load and development of cervical intraepithelial neoplasia and cervical cancer.

The aim of the present study was to evaluate the relationship between human papillomavirus (HPV) viral load and risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. HPV viral load was tested by hybrid capture (HC) II method in 69 normal women, 202 with CIN, and 236 with squamous cervical cancer (SCC). A significant difference in viral load was found between CIN I and CIN II + III. The risk of developing CIN and SCC estimated by OR (odds ratio) increased with elevated viral load (medium viral load: 13.6 for CIN and 54.6 for SCC, high viral load: 10.8 for CIN and 34.8 for SCC, respectively), with correspondent ORs (medium viral load: 11.3 for CIN and 69.4 for SCC, high viral load: 9.8 for CIN and 39.9 for SCC, respectively) after adjusted cofactors such as age, pregnancy, and so on. Hence, HPV viral load detected by HC II might be a useful predictor for women with high risk of development of CIN and cervical cancer.

Shanxi Province cervical cancer screening study II: self-sampling for high-risk human papillomavirus compared to direct sampling for human papillomavirus and liquid based cervical cytology.

The objective of this study was to compare the sensitivity and specificity of a new method for self-sampling for high risk human papillomavirus (HPV) with direct sampling and liquid based cervical cytology. In Shanxi Province, China, 8,497 women (ages 27-56) underwent a self-sample for HPV using a conical-shaped brush placed into the upper vagina and rotated. Three to sixteen months later the women were screened with liquid-based cytology and direct HPV tests. Subjects with any abnormal test underwent colposcopy and multiple biopsies. Mean age was 40.9 years. 4.4 percent of subjects had >or=CIN II, 26% a positive self-sample and 24% a positive direct test for HPV. The sensitivity for detection of >or=CIN II was 87.5% for self-sampling, and 96.8% for the direct test (P < 0.001). The specificity was 77.2% for the self-sample and 79.7% for the direct test. With an abnormal Pap defined as ASCUS or greater the sensitivity of the Pap for the detection of >CIN II was 88.3% and the specificity was 81.2%. We conclude that self-sampling for HPV is less sensitive for >CIN II than the direct test, but similar to liquid based cytology.

Free anterolateral thigh flap for extremity reconstruction: clinical experience and functional assessment of donor site.

From August of 1995 through July of 1998, 38 free anterolateral thigh flaps were transferred to reconstruct soft-tissue defects. The overall success rate was 97 percent. Among 38 anterolateral thigh flaps, four were elevated as cutaneous flaps based on the septocutaneous perforators. The other 34 were harvested as myocutaneous flaps including a cuff of vastus lateralis muscle (15 to 40 cm3), either because of bulk requirements (33 cases) or because of the absence of a septocutaneous perforator (one case). However, vastus lateralis muscle is the largest compartment of the quadriceps, which is the prime extensor of the knee. Losing a portion of the vastus lateralis muscle may affect knee stability. Objective functional assessments of the donor sites were performed at least 6 months postoperatively in 20 patients who had a cuff of vastus lateralis muscle incorporated as part of the myocutaneous flap; assessments were made using a kinetic communicator machine. The isometric power test of the ratios of quadriceps muscle at 30 and 60 degrees of flexion between donor and normal thighs revealed no significant difference (p > 0.05). The isokinetic peak torque ratio of the quadriceps and hamstring muscles, including concentric and eccentric contraction tests, showed no significant difference (p > 0.05), except the concentric contraction test of the quadriceps muscle, which revealed mild weakness of the donor thigh (p < 0.05). In summary, the functional impairment of the donor thighs was minimal after free anterolateral thigh myocutaneous flap transfer.

Important ECG diagnosis-aiding indices of ventricular septal defect children with or without congestive heart failure.

In this paper we perform a statistical study of the conventional RR intervals and two newly defined PR' and RT intervals of ECG data. A quadratic classification rule is applied to extract several important ECG diagnosis-aiding indices among normal children and children with ventricular septal defect (VSD) with or without congestive heart failure (CHF). The results show that certain statistics computed from PR', RR and RT intervals are important diagnosis-aiding indices. Best classification vectors are searched for pairwise classification. Two methods, minimum distance criterion and a two-stage classification procedure, are considered for three-way classification. Furthermore, logistic regression models based on transformations of these important diagnosis-aiding indices are proposed. The receiver operating characteristic curves of the proposed models show better performance than those of linear and quadratic logistic models. In order to proceed with this study, a computer algorithm to automatically detect the three intervals is developed and the related ECG data are collected and analysed. The algorithm is also enhanced with an outlier detection procedure for the automatic measurements of the PR' and RT intervals.

1-Methylpyrrolidine-2-acetic Acid is not a Precursor of Tropane Alkaloids.

1-Methylpyrrolidine-2-acetic acid and related compounds were studied as precursors in the biosynthesis of the tropane alkaloids in Erythroxylum coca and Datura innoxia. (R,S)-[1',2-(13)C2,2-(14)C,(15)N]-1-methylpyrrolidine-2- acid, (R,S)-[1',2'-(13)C2,1'-(14)C]-1-methylpyrrolidine-2-acetic acid, (R,S) [1',2'-(13)C2,1-(14)C]-1-methylpyrrolidine-2-acetate, and (R,S)-+2'-(14)C] methylpyrrolidine-2-acetic acid N-acetylcysteamine thioester were synthesized an intact plants by leaf-planting or hydroponic-feeding. Specific incorporation of compounds into ( - )-hyoscyamine, ( - )-scopolamine, ( - )-cocaine and the biosynthetically related cuscohygrine were very low. These results indicate that 1-methylpyrrolidine acid is not an efficient precursor of tropane alkaloids.

Characterization of the human blood coagulation factor X promoter.

Blood coagulation Factor X is a serine protease required for both the intrinsic and extrinsic pathways of coagulation. The gene for Factor X spans 27 kilobases and is located on chromosome 13, in close proximity to the gene encoding Factor VII. Expression of Factor X is restricted to the liver. We have characterized the human Factor X promoter by mapping the start sites of transcription and carrying out a functional analysis of the promoter. The first 279 base pairs (bp) of 5'-flanking sequence upstream from the first AUG are sufficient to confer maximal promoter activity in HepG2 cells. Protein-binding sites within the 279-bp fragment are defined using gel mobility shift assays. Mutagenesis of two specific sequences within the 279-bp fragment (CCAAT at -120 to -116, and ACTTTG at -56 to -51), results in loss of ability to bind proteins from a HepG2 nuclear extract, and profound reduction in promoter activity of the 279-bp fragment. We conclude that these two protein-binding sites are critical for the activity of the Factor X promoter.

Functional consequences of an arginine180 to glutamine mutation in factor IX Hilo.

Factor IX Hilo is a variant factor IX molecule that has no detectable coagulant activity. The defect in factor IX Hilo arises from a point mutation in the gene such that in the protein Arg180 is converted to a Gln. Activation of factor IX Hilo by factor Xla was monitored using the fluorescent active site probe p-aminobenzamidine. Normal factor IX showed complete activation in one hour as determined by measuring the increase in fluorescence when p-aminobenzamidine bound to activated factor IX. Factor IX Hilo showed no increase in fluorescence even after 24 hours, indicating that the active site was not exposed. Polyacrylamide gel electrophoresis showed that factor IX Hilo was cleaved to a light chain plus a larger peptide with a molecular weight equivalent to a heavy chain covalently linked to an activation peptide. Amino terminal amino acid sequencing of factor IX Hilo cleaved by factor Xla showed cleavage only at Arg145-Ala146, indicating that the Gln180-Val181 bond was not cleaved and that the active site was thus not exposed. The presence of factor IX Hilo in patient plasma was responsible for the patient having a very long ox brain prothrombin time characteristic of severe hemophilia Bm. Patient plasma had an ox brain prothrombin time of 100 seconds using a Thrombotest kit, significantly prolonged over the normal control value of 45 seconds. When factor IX Hilo was depleted from patient plasma using an immunoaffinity column, the ox brain prothrombin time decreased to 41 seconds. When factor IX Hilo was added back to depleted patient plasma, to normal plasma depleted of factor IX by the same affinity column, or to plasma from a CRM- hemophilia B patient, the ox brain prothrombin time was significantly prolonged. We conclude that the Arg180 to Gln mutation in factor IX Hilo results in a molecule that cannot be activated by factor Xla. Further, our data suggest that the mutation results in a molecule that interacts with components of the extrinsic pathway to give a prolonged ox brain prothrombin time.