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Tricuspid annular plane systolic excursion (TAPSE) is usually measured with M-mode using sector line, however, this may not align with the anatomical shortening of the right ventricular (RV). In this study, we compared the different methods to measure TAPSE using three different reference lines (sector line, anatomical line, and apico-annular line). We included 148 patients diagnosed with pulmonary arterial hypertension (PAH) who underwent TTE and right heart catheterization within 2 weeks of each other. TAPSE was measured by M-mode (sector, anatomical), 2D (sector, anatomical), or as tricuspid apico-annular displacement (TAAD). Agreement between measures was assessed using coefficient of variation (COV), Spearman's correlation, and Bland-Altman analysis. Receiver-operating characteristics and Kaplan-Meier analysis were used to explore associations with the combined outcome of death or lung transplantation at 5 years. There was a good concordance between anatomical and sector M-mode with a COV of 15.5 ± 1.6% and a bias of -0.6 ± 3.2 mm. In contrast, anatomical M-mode TAPSE and TAAD differed significantly with the mean difference of 3.3 ± 3.8 mm (COV 30.5 ± 6.1%; p  < 0.0001). Among the different 2D methods, anatomical 2D agreed well with anatomical M-mode TAPSE (COV of 11.8 ± 2.0%; r  = 0.89; p  < 0.0001). Among the five methods, TADD had the strongest association with the combined endpoint of death or transplantation at 5 years (C-statistic 0.64, 95% confidence interval [CI] 0.57-0.71). We concluded that different measures of TAPSE are not interchangeable., Competing Interests: Dr. Haddad reports research grants from Actelion Pharmaceuticals, a Janssen Company of Johnson & Johnson, focused on computational approaches for the diagnosis and monitoring of pulmonary hypertension. The other authors report no conflicts relevant to this study., (© 2024 The Author(s). Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Several indices of right heart remodeling and function have been associated with survival in pulmonary arterial hypertension (PAH). Outcome analysis and physiological relationships between variables may help develop a consistent grading system. Patients with Group 1 PAH followed at Stanford Hospital who underwent right heart catheterization and echocardiography within 2 weeks were considered for inclusion. Echocardiographic variables included tricuspid annular plane systolic excursion (TAPSE), right ventricular (RV) fractional area change (RVFAC), free wall strain (RVFWS), RV dimensions, and right atrial volumes. The main outcome consisted of death or lung transplantation at 5 years. Mathematical relationships between variables were determined using weighted linear regression and severity thresholds for were calibrated to a 20% 1-year mortality risk. PAH patients ( n  = 223) had mean (SD) age of 48.1 (14.1) years, most were female (78%), with a mean pulmonary arterial pressure of 51.6 (13.8) mmHg and pulmonary vascular resistance index of 22.5(6.3) WU/m 2 . Measures of right heart size and function were strongly related to each other particularly RVFWS and RVFAC ( R 2  = 0.82, p  < 0.001), whereas the relationship between TAPSE and RVFWS was weaker ( R 2  = 0.28, p  < 0.001). Death or lung transplantation at 5 years occurred in 78 patients (35%). Guided by outcome analysis, we ascertained a uniform set of parameter thresholds for grading the severity of right heart adaptation in PAH. Using these quantitative thresholds, we, then, validated the recently reported REVEAL-echo score (AUC 0.68, p  < 0.001). This study proposes a consistent echocardiographic grading system for right heart adaptation in PAH guided by outcome analysis., Competing Interests: Bettia Celestin, Shadi P. Bagherzadeh, Kenzo Ichimura, Everton J. Santana, Andrew John Sweatt and Pablo Amador Sanchez, have no conflicts to report. Francois Haddad has received funding from Janssen Inc. to conduct the research. Tobore Tobore is a senior director of Medical Affairs at Janssen. Anton Vonk Noordegraaf is supported by the Netherlands CardioVascular Research Initiative (CVON‐2012‐08 PHAEDRA, CVON‐2017‐10 DOLPHIN‐GENESIS) and the Netherlands Organization for Scientific Research (NWO‐VICI: 918.16.610). In addition, his institute received speakers money from Johnson & Johnson, MSD, Actelion, Bayer and Ferrer in the past 3 years. Finally, he served as a member of the scientific advisory board of Morphogen‐X, Ferrer, Gosammer Bio Services Inc, Altavant, MSD and Johnson & Johnson. The remaining authors declare no conflict of interest., (© 2024 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: Transcriptional repressor GATA binding 1 (TRPS1) is a transcription factor recently shown to play a role in the development of breast and liver cancer. Here, we evaluate TRPS1 immunoexpression in normal skin tissues and various cutaneous tumors., Methods: TRPS1 immunohistochemistry was performed in 109 cases of primary cutaneous tumors and 19 cases of metastatic carcinomas. TRPS1 expression was also evaluated in the normal skin tissues., Results: The normal epidermis was TRPS1-. In contrast, the eccrine apparatus, epithelial compartment of the hair follicles, hair papilla, sebaceous glands, and anogenital mammary-like glands were TRPS1+. In primary cutaneous tumors, TRPS1 positivity varied in poroma (2/3), nodular hidradenoma (4/5), spiradenoma (4/4), cutaneous mixed tumor (5/5), trichilemmal cyst (7/8), proliferating trichilemmal tumor (1/3), pilomatricoma (9/9), sebaceoma (2/5), extramammary Paget disease (13/13), sebaceous carcinoma (2/2), actinic keratosis (3/10), Bowen disease (7/12), and squamous cell carcinoma (1/5) cases. All cases of seborrheic keratosis, basal cell carcinoma, Merkel cell carcinoma, and malignant melanoma were TRPS1-. All metastatic breast carcinoma cases (8/8) were highly positive for TRPS1, while all but one of the other metastatic tumor cases were TRPS1-., Conclusions: TRPS1 immunoexpression was observed in several skin appendages and cutaneous tumors., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Ventricular interdependence plays an important role in pulmonary arterial hypertension (PAH). It can decrease left ventricular (LV) longitudinal strain (LVLS) and lead to a leftward displacement ("transverse shortening") of the interventricular septum (sTS). For this study, we hypothesized the ratio of LVLS/sTS would be a sensitive marker of systolic ventricular interactions in PAH. In a cross-sectional cohort of patients with PAH ( n  = 57) and matched controls ( n  = 57), we quantified LVLS and septal TS in the amplitude and time domain. We then characterized LV phenotypes using upset plots, ventricular interactions using network analysis, and longitudinal analysis in a representative cohort of 45 patients. We also measured LV metrics in mice subjected to pulmonary arterial banding (PAB) using a 7 T magnetic resonance imaging at baseline, Week 1, and Week 7 post-PAB ( N  = 9). Patients with PAH had significantly reduced absolute LVLS (15.4 ± 3.4 vs. 20.1 ± 2.3%, p  < 0.0001), higher sTS (53.0 ± 12.2 vs. 28.0 ± 6.2%, p  < 0.0001) and lower LVLS/sTS (0.30 ± 0.09 vs. 0.75 ± 0.16, p  < 0.0001) compared to controls. Reduced LVLS/sTS was observed in 89.5% of patients, while diastolic dysfunction, impaired LVLS (<16%), and LV atrophy were observed in 73.7%, 52.6%, and 15.8%, respectively. In the longitudinal cohort, changes in LVLS/sTS were closely associated with changes in N-terminal pro B-type natriuretic peptide ( r  = 0.73, p  < 0.0001) as well as survival. Mice subjected to PAB showed significant RV systolic dysfunction and decreased LVLS/sTS compared to sham animals. We conclude that in PAH, LVLV/sTS is a simple ratio that can reflect ventricular systolic interactions., Competing Interests: Francois Haddad reports research grants from Actelion Pharmaceuticals, a Janssen Company of Johnson & Johnson focused on computational approaches for the diagnosis and monitoring of pulmonary hypertension. The other authors declare no conflict of interest., (© 2023 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: The podocyte slit diaphragm (SD) is an essential component of the selective filtration barrier in the glomerulus. Several structural proteins required for formation and maintenance of SD have been identified; however, molecular mechanisms regulating these proteins are still limited., Results: Here, we demonstrate that MAGUK p55 subfamily member 5a (Mpp5a)/Nagie oko, a component of the Crb multi-protein complex, was colocalized with an SD-associated protein ZO-1 in the zebrafish pronephric glomerulus. To characterize the function of Mpp5a, zebrafish mpp5a(m520) mutant embryos, which are known to have defects in cardiac and neuronal morphogenesis, were analyzed. These mutants failed to merge the bilateral glomerular primordia and to form the glomerular capillary and mesangium, but the foot processes and SD showed normal appearance. The structural disorganization in the mpp5a(m520) mutant glomerulus was quite similar to that of a cardiac troponin T2a/tnnt2a/silent heart knockdown zebrafish, which exhibited circulatory failure due to lack of heart beating., Conclusions: Mpp5a is not prerequisite to form podocyte slit diaphragm in the pronephric glomerular development in zebrafish. The structural disorganization of the pronephric glomerulus in the mpp5a(m520) mutant is likely to result from circulatory failure, rather than the anomaly of Mpp5a protein in the glomerulus., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Blastic natural killer (NK) cell lymphoma/leukemia (BNKL) is an immature CD56-positive neoplasm, which was recognized recently and characterized by systemic proliferation of tumor cells including skin, lymph node, and bone marrow., Methods: The current study analyzed 47 patients with BNKL (27 had leukemias and 20 had lymphomas). Patient data were collected for the survey of the NK-Cell Tumor Study Group., Results: There were 33 males and 14 females, with a median age of 53 years (range, 3 months to 89 years). There were few clinicopathologic differences between the leukemia and lymphoma types. Cutaneous involvement was noted at diagnosis in 28 patients, who presented a tendency for older age of onset (median: 56 vs. 46 years, P = 0.11) than patients with noncutaneous BNKL. Cutaneous BNKL showed less frequent mediastinal involvement (4% vs. 53%, P = 0.0002) and less severe thrombocytopenia (P =0 .03). Phenotypic characteristics were also different, with cutaneous BNKL favoring CD4 and HLA-DR expression, and noncutaneous BNKL favoring CD16 and CD34 expression. Both groups responded well to chemotherapy for lymphoid malignancies, but disease recurrence was frequent. The prognosis of patients with noncutaneous BNKL was significantly poorer than that of patients with cutaneous BNKL (median survival: 15 vs. 25 months, P = 0.02). Multivariate analysis confirmed that cutaneous involvement was a significant and independent prognostic factor for BNKL, as were age of onset and leukocyte count., Conclusions: These findings suggested that BNKL is a heterogeneous disease and contains at least two subtypes. Although further investigations are needed to settle a marker for distinction, the presence of cutaneous involvement is a useful prognostic factor.

Background: A wide variety of modalities, including surgery, radiation therapy, and chemotherapy, alone or in combination, have been used for the treatment of squamous cell carcinoma (SCC) of the maxillary sinus to obtain better local control and maintain functions. However, there is still much controversy with regard to the optimum treatment., Methods: From 1987 to 1999, 33 patients with SCC of maxillary sinus were treated at the Department of Otolaryngology-Head and Neck Surgery, University of Tokyo Hospital. The treatment consisted of 30-40 grays (Gy) of preoperative radiotherapy with concomitant intraarterial infusion of 5-fluorouracil and cisplatin followed by surgery and 30-40 Gy of postoperative radiotherapy, for tumors without skull base invasion. For tumors invading the skull base, preoperative systemic chemotherapy with or without radiotherapy was performed, instead of intraarterial chemotherapy, then followed by skull base surgery. The surgical procedures varied according to the extent of tumor. Results were compared with those of the 108 patients treated in our hospital from 1976 to 1982., Results: Partial maxillectomy was performed in 2 T2 patients and 12 T3 patients. Total maxillectomy was performed in 1 T2 patient, 3 T2 patients, and 7 T4 patients. Skull base surgery was performed in eight T4 patients. Orbital content and hard palate were preserved in 22 patients and 18 patients, respectively. The overall 5-year survival rates were 86% in T 3 patients and 67 % in T4 patients, respectively., Conclusions: Our multimodal treatment has provided favorable local control and survival outcome with good functional results., (Copyright 2002 American Cancer Society.)

Acid amplifiers derived from a certain class of sulfonates suffer from autocatalytic decomposition in the presence of a strong acid to give corresponding sulfonic acids, which catalyze the decomposition of the parent sulfonates, leading to the liberation of more of the same sulfonic acids in an exponential manner. Five types of acid amplifiers displaying acid proliferation reactions are presented. A certain type of carbamate exhibits autocatalytic fragmentation to give the corresponding aliphatic amine and olefin together with carbon dioxide, whereas the generated amine is able to act as a catalyst for the fragmentation so that the carbamates are referred to as base amplifiers. Applications of acid and base amplifiers to photofunctional materials, including photoresists, are described as a consequence of the combination of the molecular amplifiers with photoacid as well as photobase generators. Practical applications of acid proliferation reactions in polymer films are discussed., (Copyright 2002 The Japan Chemical Journal Forum and John Wiley & Sons, Inc.)

Objective: Stomal recurrence after total laryngectomy is one of the most serious issues in the management of laryngeal carcinoma. The management of stomal recurrence, including chemotherapy, radiotherapy, and surgery, has been reported as unsatisfactory., Study Design and Setting: From 1985 to 1995, 69 patients underwent total laryngectomy for the treatment of laryngeal cancer at the University of Tokyo Hospital. To identify the risk factors for stomal recurrence, we analyzed these patients according to various clinicopathological factors., Results: Stomal recurrence developed in 6 of 69 patients who underwent total laryngectomy for laryngeal carcinoma. Statistical analysis reveals that primary site, preoperative tracheotomy, and paratracheal lymph node metastasis are significant risk factors for stomal recurrence., Conclusion: Intensive follow-up should be performed for patients with glottic carcinoma who had preoperative tracheotomy, paratracheal lymph node metastasis, or both to detect stomal recurrence at an early stage.

Background: Low grade mucosa-associated lymphoid tissue (MALT) lymphomas usually are confined to single extranodal organs. Although some case reports have been published, clinicopathologic characteristics of multiorgan MALT lymphomas remain unclear., Methods: The authors evaluated 7 MALT lymphoma cases involving multiorgans in the past 7 years. In this period, they experienced 304 cases of MALT lymphomas. They analyzed the clinicopathologic features of these cases, including examination of clonal comparison among the lesions., Results: The patients, 4 females and 3 males, were aged 55-68 years old (average, 60.1 years). Four cases showed multiple organ involvement at the initial diagnosis or after a short period. In the other three cases, primary foci were the stomach, thyroid gland, and ocular adnexa; after a rather long period (3 years or more), distant metastases were found. Although intestinal primary lymphomas are rather rare, six of the seven cases showed large intestinal involvement. Lymph node involvement was proven in only three cases. The patients were rather resistant to the various therapeutic approaches. Although six patients are alive, five are with disease. DNA analyses revealed that in five of the cases evaluated, identical clones were detected among the different affected organs., Conclusions: Multiorgan MALT lymphomas are rather rare. Most cases probably derived from a single clone, and lymphoma cells may selectively move among MALTs via a homing system with preferential involvement of the colon. Because multiorgan MALT lymphomas rarely achieve complete remission by treatment with combination chemotherapy or irradiation, MALT lymphomatous lesions should be checked carefully, especially in the large intestine.

Background: Current goals for the treatment of carcinoma of the maxillary sinus include the preservation of vision, ability to eat, ability to communicate, and appearance as well as cure., Methods: Seventy-five Japanese patients who presented with maxillary sinus carcinoma between 1979 and 1997 were analyzed retrospectively. There were 48 males and 27 females with a median age of 62 years. The mean follow-up period was 73 months. All patients underwent multimodality therapy including surgery through a sublabial incision, radiotherapy, and regional chemotherapy. The regional lymph nodes were treated only in those patients with cervical lymph node involvement., Results: The 5-year and 10-year overall survival rates were 76% and 66%, respectively. In 65 patients with squamous cell carcinoma, the 5-year and 10-year overall survival rates were 77% and 66%, respectively. All 23 patients with orbital involvement retained the orbital contents and 17 patients demonstrated adequate ocular function. There was no disease recurrence reported among patients with involvement of the foramen rotundum or the foramen ovale, whereas two of the three patients with invasion of the foramen lacerum developed disease recurrence. There were 12 complications in 12 patients, including double vision (4 patients), cataracts (3 patients), trismus (4 patients), and fistula formation (1 patient)., Conclusions: Control of the primary tumor site is important in the curative treatment of patients with maxillary sinus carcinoma. Combined therapy with conservative surgery, radiotherapy, and regional chemotherapy appears to be an effective method for local control and the preservation of ocular function., (Copyright 2000 American Cancer Society.)

Background: p27, a cyclin-dependent kinase inhibitor, regulates progression from G1 to S phase. There have been a few clinical reports of low p27 expression associated with poor survival among patients with cancer; however, there have been no reports of such an association in cases of head and neck cancer. The authors investigated whether p27 expression in patients with oral tongue squamous cell carcinoma was associated with their prognosis., Methods: Ninety-four patients with oral tongue squamous cell carcinoma were analyzed. The authors performed p27 immunohistochemistry on all patients and Western blot analysis on 19 available patients. Cox proportional hazards regression analysis that included gender, history of smoking and alcohol usage, presence of multiple primary cancers, stage, histologic grade, and p27 status was used to identify the multivariate predictive value of prognostic factors., Results: Twenty-six patients had high p27 expression (> or =50% tumor cell nuclei positive), and 68 patients had low p27 expression (<50%) by immunohistochemistry. In those with low p27 expression, N(+) and advanced T (T3 or T4) were significantly higher than in those with high p27 expression (P = 0.02 and 0.04). The 5-year survival rate in the low p27 group was 44%, whereas that in the high p27 group was 68%, indicating a significant difference (P = 0.04). p27 expression was inferred from Western blot analysis, and an arbitrary quantity (<1, 1-5, or > or =5) from the ratio of tumor to normal tissue density was used to characterize, resulting in 8 (42%), 3 (16%), and 8 (42%) patients in the low (<1-fold), intermediate (1-5-fold), and high (> or =5-fold) groups, respectively. Results of immunohistochemical analysis for p27 were significantly correlated with those of Western blot analysis (P = 0.02). Multivariate analysis revealed that low intensity of p27 expression and advanced stage (Stage III or IV) were predictors of reduced survival (P = 0.02 and 0.001)., Conclusions: Low p27 expression was associated with increasing lymph node metastasis and stage of tumor and resulted in a poor prognosis for patients with oral tongue squamous cell carcinoma. p27 is apparently a significant predictor of survival.

To examine the presence of substances which inhibit calcification in human ligamentum flavum, the inhibitory effect of an Na2HPO4 extract of the flavum was determined in terms of the in vitro calcium uptake of the ligamentum flavum matrix. Additionally, grafts of extracted and non-extracted dry ligamentum flavum matrices were transplanted into the dorsal muscles of rats, and calcification in the grafts was examined radiologically and histochemically. In order to determine if component cells of human ligamentum flavum produce calcification inhibitors, ligamentum flavum cells were cultured, and the crystal inhibitor activity of the culture medium was measured by a seed test which used hydroxyapatite as the nucleus of precipitation. The calcification reaction system demonstrated that the ligamentum flavum extract contains an inhibitory factor for calcium uptake by the ligamentum flavum matrix. The seed test revealed that human ligamentum flavum cells produce calcification inhibitor activity.

The effective diffusivity of oxygen, D(e), in Ca-alginate and PVA-SbQ gels was measured using a two-chamber vessel with a membrane between the two chambers. The effect of cell density, C(c), on D(e) in Ca-alginate gels was studied. The effective diffusivity of oxygen decreased with increasing cell density, to C(c) = 170 kg dry cells/m(3) gel. The dependency of D(e) on cell density was discussed in terms of a random-pore model. The model correlated well with experimental data, i.e., kD(e)/D(0) = 0.86(1 - 1.47 x 10(-3) C(c))(2). Here, k is the partition coefficient, and D(0) is diffusivity in water.