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Detection of pulmonary metastases with multi-detector row CT scans of 5-mm nominal section thickness: autopsy lung study.

PURPOSE: To determine the effect of changing pitch and collimation on depiction of pulmonary metastases on scans of 5-mm section thickness obtained with multi-detector row computed tomography (CT) compared with those obtained with single-detector row CT. MATERIALS AND METHODS: In five autopsy lungs, 1,013 metastatic 0.5-30.0-mm nodules were detected at helical CT with 1-mm collimation and histopathologically diagnosed as metastases. Each nodule was numbered, and its localization was recorded as the standard for subsequent studies. Four types of scans of 5-mm section thickness were obtained with multi-detector row CT and four sets of helical pitch and table speed, respectively, as follows: set A, 3:1 and 7.5 mm per rotation; set B, 6:1 and 15 mm per rotation; set C, 6:1 and 30 mm per rotation; set D, conventional and 5-mm interval. Conventional helical CT scans (set E) were obtained with 5-mm collimation at single-detector row CT. Two independent observers evaluated the five sets of CT scans. RESULTS: Acquisition times for sets A-D, respectively, were 1.9, 3.8, 7.5, and 1.5 times faster than they were for set E. The mean numbers of detected nodules were 671 (66%) in set A, 661 (65%) in set B, 678 (67%) in set C, 654 (65%) in set D, and 656 (65%) in set E; there was no significant difference in the number of detected nodules among the five sets (P =.997, McNemar test and Bonferroni equation). CONCLUSION: Regardless of varying pitch or detector collimation, multi- and single-detector row CT scans obtained with 5-mm section thickness have almost the same ability to depict pulmonary metastases and are equivalent.

Autopsy↗

Echocardiography in chronic aortic insufficiency. Is valve replacement too late when left ventricular end-systolic dimension reaches 55 mm?

To determine whether a ventricular (LV) end-systolic dimension (ESD) greater than or equal to 55 mm and LV left fractional shortening less than 25% are risk factors for aortic valve replacement (AVR) in patients with aortic insufficiency, we analyzed the clinical course and M-mode echocardiograms in 47 consecutive patients who underwent AVR for isolated symptomatic AI. Group 1 patients (n = 27) had a preoperative ESD less than 55 mm (mean 44 mm, range 30-52 mm) and group 2 patients (n = 20) had a preoperative ESD greater than or equal to 55 mm (mean 62 mm, range 55-85 mm). One patient in group 1 and 10 patients in group 2 had left ventricular fractional shortening less than 25%. There were no perioperative or postoperative deaths during an average follow-up of 41 months (range 6-76 months). Five patients had perioperative myocardial infarctions (MIs), three in group 1 and two in group 2. Since myocardial protection with cold potassium cardioplegia was instituted, no patient has suffered a perioperative MI. The average preoperative New York Heart Association functional classification was 2.3 (group 1) and 2.6 (group 2). Postoperatively, it was 1.2 in group 1 and 1.1 in group 2. Thirty-three patients (20 in group 1 and 13 in group 2) had echocardiograms at least 1 year after AVR. Of these, LV-end diastolic dimension decreased fro 67 +/- 6 to 53 +/- 6 mm (mean +/- SD) in group 1 (p less than 0.001) and from 79 +/- 3 to 55 +/- 6 mm in group 2 (p less than 0.001). The LVESD also decreased, but this is difficult to interpret because of frequent postoperative abnormal interventricular septal motion. The LV cross-sectional area, an index of LV mass, decreased in group 1 from 25 +/- 5 to 20 +/- 5 cm2 (p lss than 0.001) and in group 2 from 32 +/- 9 to 20 +/- 5 cm2 (p less than 0.001). Postoperative end-diastolic dimension and cross-sectional area were not significantly different between the two groups. We concluded that in aortic insufficiency, a preoperative ESD greater than or equal to 55 mm does not preclude successful AVR, as judged by long-term survival, symptomatic relief, and normalization of LV dimensions assessed by echocardiography.

Adult↗

Biomechanical comparison of the bioabsorbable RetroScrew system, BioScrew XtraLok with stress equalization tensioner, and 35-mm Delta Screws for tibialis anterior graft-tibial tunnel fixation in porcine tibiae.

BACKGROUND: Achieving effective soft tissue graft-tibial tunnel fixation remains problematic. HYPOTHESIS: No differences would exist for tibialis anterior graft-tibial tunnel fixation when comparing the RetroScrew System (20-mm retrograde screw, 17-mm antegrade screw), the 35-mm tapered Delta Screw (manual tensioning), and the 35-mm BioScrew XtraLok (applied using an instrumented tensioner). STUDY DESIGN: Controlled laboratory study. METHODS: Porcine tibiae (apparent bone mineral density, 1.3 g/cm(2)) and human tendon allografts were divided into 3 matched groups of 6 specimens each before cyclic (500 cycles, 50-250 N, 1 Hz) and load-to-failure (20 mm/min) tests. RESULTS: The BioScrew XtraLok (210.9 +/- 54.9 N/mm) and the 35-mm Delta Screw (224.3 +/- 43.7 N/mm) displayed superior stiffness to the RetroScrew System (114.1 +/- 23.3 N/mm) (P = .0004) during cyclic testing. The BioScrew XtraLok (1.0 +/- 0.2 mm) and the Delta Screw (0.9 +/- 0.2 mm) also displayed less displacement during cyclic testing than the RetroScrew System (1.8 +/- 0.5 mm) (P = .001). During load-to-failure testing, the BioScrew XtraLok withstood greater loads (1436.3 +/- 331.3 N) (P = .001) and displayed greater stiffness (323.6 +/- 56.8 N/mm) (P = .002) than the 35-mm Delta Screw (load, 1042.2 +/- 214.4 N; stiffness, 257.2 +/- 22.2 N/mm) and the RetroScrew System (load, 778.7 +/- 177.5 N; stiffness, 204.4 +/- 52.9 N/mm). CONCLUSION: The BioScrew XtraLok with instrumented tensioning displayed superior fixation to the RetroScrew System and the 35-mm Delta Screw applied with manual tensioning. CLINICAL RELEVANCE: The BioScrew XtraLok may provide superior soft tissue graft-tibial tunnel fixation. Further in vitro studies using human tissue and in vivo clinical studies are needed.

Absorbable Implants↗

Targeting mitochondrial factor Smac/DIABLO as therapy for multiple myeloma (MM).

Second mitochondria-derived activator of caspases (Smac) promotes apoptosis via activation of caspases. Here we show that a low-molecular-weight Smac mimetic LBW242 induces apoptosis in multiple myeloma (MM) cells resistant to conventional and bortezomib therapies. Examination of purified patient MM cells demonstrated similar results, without significant cytotoxicity against normal lymphocytes and bone marrow stromal cells (BMSCs). Importantly, LBW242 abrogates paracrine MM cell growth triggered by their adherence to BMSCs and overcomes MM cell growth and drug-resistance conferred by interleukin-6 or insulinlike growth factor-1. Overexpression of Bcl-2 similarly does not affect LBW242-induced cytotoxicity. Mechanistic studies show that LBW242-induced apoptosis in MM cells is associated with activation of caspase-8, caspase-9, and caspase-3, followed by PARP cleavage. In human MM xenograft mouse models, LBW242 is well tolerated, inhibits tumor growth, and prolongs survival. Importantly, combining LBW242 with novel agents, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or the proteasome inhibitors bortezomib and NPI-0052, as well as with the conventional anti-MM agent melphalan, induces additive/synergistic anti-MM activity. Our study therefore provides the rationale for clinical protocols evaluating LBW242, alone and together with other anti-MM agents, to improve patient outcome in MM.

Animals↗

Smallest cystic tumor, measuring 5 mm, was identified as an invasive adenocarcinoma among multiple intraductal papillary-mucinous tumors.

We encountered a case of four cysts of intraductal papillary-mucinous tumor in the pancreas, a 25-mm diameter tumor, a 20-mm tumor, and a 10-mm tumor in the pancreatic body and tail, and a 5-mm diameter tumor in the uncinatus process, and the smallest diameter intraductal papillary-mucinous tumor (5 mm) was regarded as an invasive papillary adenocarcinoma, while the other three intraductal papillary-mucinous tumors were adenomas. A 63-year-old asymptomatic male was indicated of the presence of multiple pancreatic tumors by computed tomography during a physical examination. Endoscopic retrograde cholangiopancreatography revealed three cysts (25 mm, 20 mm, 10 mm diameter tumor) in the pancreatic body and tail, and one cyst 5 mm) in the uncinatus process. Cytologic examination of the pancreatic juice determined them as Class V. Based on a diagnosis of malignant intraductal papillary-mucinous tumors, he underwent distal pancreatectomy with removal of the uncinatus process. Pathologically, three cysts in the body and tail of the pancreas were found to be adenomas, but the 5-mm cyst in the uncinatus process was found to be an invasive intraductal papillary-mucinous tumor. The interstitium had been invaded by cancer, and the uncinatus process was the cancer positive surgical margin, and cystological examination of the pancreatic juice through repeated endoscopic retrograde cholangiopancreatography resulted in a class V, so the patient underwent a total pancreatectomy. When diagnosing intraductal papillary-mucinous tumor(s), there is the possibility of incorrectly differentiating between benignancy and malignancy when the diagnosis is based on cyst diameter, as is conventional.

Adenocarcinoma↗

Extent of vascularization as a prognostic indicator in thin (< 0.76 mm) malignant melanomas.

Angiogenesis in malignant melanoma (MM) was evaluated by comparing mean vessel number (MVN) in Spitz's nevi (SN), thick and thin MMs that metastasized, and thick and thin MMs with > or = 10-year survival. Vessels were identified with antibodies against factor VIII-related antigen (FVIII) and CD34 in 37 MMs (17 < or = 1.9 mm and 20 > or = 4.0 mm) with > or = 10-year follow-up and 10 SN from children (< or = 9 years old). Fields (x250) with the highest vessel density were counted by independent observers blinded to clinical outcome. There were no differences in MVN between SN versus MMs (P = 1.0), but the distribution of vessels was much more uniform in SN. Seven MM pairs (> or = 5.5 mm) and five pairs (< or = 0.75 mm) were matched by sex, age, site, stage, and primary treatment (paired t-test). In the pairs > or = 5.5 mm, there was no correlation with MVN with either metastasis or death (FVIII P = 0.98; CD34 P = 0.85). Among the thin paired lesions, high MVN (FVIII = 46, CD34 = 39) was significantly related not only to metastasis (FVIII P = 0.04, CD34 P = 0.03) but also to death (FVIII P = 0.04, CD34 P = 0.05). MVN does not separate SN versus MM nor predict outcome in thick (> or = 4.0 mm) MMs; however, high MVN (> or = 42 average) is predictive of metastasis and death in MMs < or = 0.75 mm. Larger matched studies are indicated to confirm this observation.

Adult↗

Phacotrabeculectomy: comparison of results from 3.5- and 5.2-mm incisions.

BACKGROUND AND OBJECTIVE: To compare the intraocular pressure control, visual results, and astigmatic results of 3.5-mm and 5.2-mm incisions following phacotrabeculectomy with 12 months of follow-up. PATIENTS AND METHODS: Fifty eyes underwent clear cornea punch trabeculectomy under a 5.0 x 2.5-mm scleral flap, closed with two 10-0 polyglactin sutures. The first 25 eyes underwent wound extension to 5.2 mm for insertion of a single-piece polymethylmethacrylate (PMMA) lens. The next 25 eyes underwent wound extension to 3.5 mm for insertion of a folded silicone lens. RESULTS: The mean intraocular pressure decrease from the preoperative level was 7.6 mm Hg in the 3.5-mm incision group and 7.8 mm Hg in the 5.2-mm incision group. One patient required continued medication. The best-corrected visual acuity was 20/40 or better in 86% of the patients, with no significant difference between the groups. The mean "with the wound" induced astigmatism showed no statistical difference between the two groups. CONCLUSIONS: The use of 10-0 polyglactin appears to aid filtration, yet minimizes hypotony or the need for antimetabolites. For surgeons who wish to reduce costs without compromising results during phacotrabeculectomy, there is merit in considering a 5.2-mm incision; moreover, the more rigid single-piece PMMA lens appears to be associated with fewer complications in the immediate postoperative period.

Aged↗

Opsonic activity of myeloma immunoglobulins (MM-Ig).

Patients with MM are at an increased risk for life-threatening bacterial infections, primarily by organisms that require opsonization for interaction with granulocytes. In the present study we used a neutrophil chemiluminescence (CL) assay of opsonization to explore the opsonic activity of MM-Ig for zymosan particles. Particles were treated with serum lacking in Ig to explore the contribution of Ig to zymosan opsonization. This serum was found to have 69 +/- 2.6% (X +/- SEM) of the opsonic activity of normal serum (P less than .001). Normal serum concentrations of normal IgG, MM-IgG, and MM-IgA all lacked opsonic activity for zymosan. However, when particles were treated with Nl-IgG, MM-IgG, or MM-IgA as well as complement, normal opsonic activity was generated. Increasing the concentration of the Ig to stimulate MM serum did not inhibit this opsonic activity. Thus both MM-IgG and MM-IgA can function as normal, nonspecific opsonins.

Granulocytes↗

Identification by isoelectric focusing of creatine kinase-MM isoforms in the plasma and striated muscle of pigs.

Total creatine kinase (CK) and CK-MM isoforms were determined in plasma and longissimus dorsi muscle extracts from normal pigs. Based on their total CK activity, the pigs were divided into two groups. Pigs of group 1 (n = 16) had a mean plasma total CK of 298 +/- 16 U/L and the distribution of the CK-MM isoforms was 65.7 +/- 2.5% CK-MM3, 18.9 +/- 1.6% CK-MM2 and 15.3 +/- 1.5% CK-MM. In group 2 (n = 18; 826 +/- 75 U/L total CK) four isoforms were observed: 3.1 +/- 0.9% CK-MM, 67.9 +/- 3.0% CK-MM3, 21.5 +/- 2.3% CK-MM2 and 7.5 +/- 1.3% CK-MM. The differences between the two groups of pigs were significant (p less than 0.001) for CK-MM1 and the presence of CK-MM. Four CK-MM isoforms were also detected in longissimus dorsi muscle homogenates: 45.6 +/- 8.1% CK-MM, 32.6 +/- 11.7% CK-MM3, 16.6 +/- 2.3% CK-MM2 and 5.1 +/- 2.8% CK-MM1. The release of CK-MM isoforms from muscle into plasma seems to be unrelated to the concentration of these isoforms in striated muscle.

Animals↗

Adenocarcinoma of the lower third of the rectum surgically treated with a <10-MM distal clearance: preliminary results in 35 N0 patients.

BACKGROUND: Recent reports suggest that a distal clearance (DC) of 10 mm at the lower surgical margin may be considered adequate in the surgical treatment of rectal cancer, but there are no data on the possible adequacy of a < 10-mm DC in N0 patients in whom a good prognosis can otherwise be expected, that is, those with negative surgical margins and negative lymph nodes. METHODS: Between November 1991 and December 1998, 154 consecutive patients with adenocarcinoma of the lower third of the rectum had a total rectal resection with total mesorectal excision and coloendoanal anastomosis. Among 76 N0 patients, there were 35 with <10-mm DC and 41 with > or =10-mm DC. Each group was divided into two subgroups depending on whether the surgical margins were involved or not, and the rate of local recurrence in the various categories was compared. All B2 Astler-Coller stage patients in the series received postsurgical chemoradiotherapy. RESULTS: The local recurrence rate in the 35 patients with DC < 10 mm was 11.4% and that of the 41 patients with DC > or =10 mm was 7.3%. When only patients with negative surgical margins were considered, the local recurrence rate was 3.4% for those with < 10-mm DC and 5.1% for those with > or =10-mm DC. CONCLUSIONS: Our results suggest that a radical surgery with <10-mm DC followed by chemoradiotherapy may be adequate in N0 patients, provided that a careful pathologic examination of the surgical specimen excludes the presence of lymph node metastases and that the distal rectal and mesorectal resection margins fall in healthy tissue.

Adenocarcinoma↗

Pulmonary nodules 10 mm or less in diameter with ground-glass opacity component detected by high-resolution computed tomography have a high possibility of malignancy.

OBJECTIVES: For the histological diagnosis of small lung cancers of 10 mm or less in diameter (< or =10), resection by video-assisted thoracic surgery (VATS) with computed tomography (CT)-guided marking is feasible. One problem is that a small number of these pulmonary nodules are malignant. We retrospectively analyzed CT images of pulmonary nodules to find better criteria to select candidates for resection among patients with small pulmonary nodules. METHODS: Ninety-four patients with indeterminate peripheral pulmonary nodules underwent wedge resection by VATS. High-resolution CT using a 1.25 mm slice included the area of lesions. Nodules were classified by size (< or =10, 11 to 20, >20 mm) and whether they had a ground-glass opacity (GGO) component. RESULTS: The histology of all 94 nodules showed 52 primary lung cancers, 6 metastatic tumors, 5 benign tumors, 8 intrapulmonary lymph nodes, and 23 inflammatory nodules. Ninety-three percent of nodules larger than 20 mm, 75% of nodules 10 to 20 mm, and 43% of nodules < or =10 mm were malignant. Introducing a classification according to GGO component to nodules, malignancy was detected in 88% of nodules with a GGO component and in 30% of nodules without a GGO component among nodules < or =10 mm. Nodules < or =10 mm with a GGO component showed a statistically significant (p < 0.01) correlation with malignancy. CONCLUSIONS: Pulmonary nodules < or =10 mm with GGO should be considered to have a high possibility of malignancy and to be candidates for resection by VATS.

Carcinoma, Small Cell↗

Specific inhibition by prostaglandin D2 and its metabolites of lysozyme synthesis in mouse macrophage-like cell line, Mm-1.

The cultured mouse macrophage-like cell line Mm-1 synthesizes and secretes lysozyme continuously like normal macrophages. Culture of the cells in the presence of prostaglandin D2 for 3 days strongly inhibited their production of lysozyme activity. Prostaglandin D2 caused dose-dependent inhibition of the activity: 1 X 10(-6) M prostaglandin D2 caused about 50% inhibition. Inhibition by prostaglandin D2 was not related to cytotoxicity and was reversible. The rate of synthesis of lysozyme protein was measured by culturing Mm-1 cells with radioactive amino acids and then immunoprecipitating the protein. At the concentrations used, prostaglandin D2 inhibited the synthesis of lysozyme dose-dependently, but did not suppress the synthesis of total protein. Of the various types of prostaglandin, only prostaglandin D2 inhibited the production of lysozyme in Mm-1 cells. Moreover, prostaglandin D2 did not inhibit the production of other lysosomal enzymes, such as acid proteinase, acid phosphatase and beta-glucuronidase, and did not affect Fc receptors on the cell surface, adherence of cells to the culture dish or the cell morphology. These results indicate that prostaglandin D2 specifically inhibits the synthesis of lysozyme in Mm-1 cells. When Mm-1 cells were cultured for 3 days in the presence of the ethyl acetate extract from the culture medium in which Mm-1 cells had been cultured with prostaglandin D2 for 3 days, the production of lysozyme activity of Mm-1 cells was also markedly inhibited by the extract. After the incubation of prostaglandin D2 for 3 days with Mm-1 cells, less than 10% of the initial prostaglandin D2 remained and two major metabolites appeared. These results suggest that the metabolites of prostaglandin D2 were involved in the inhibitory action of prostaglandin D2 in Mm-1 cells.

Animals↗

Creatine kinase-inhibiting monoclonal antibodies: preparation and characterization of porcine MM isoenzyme-specific antibodies.

Five monoclonal antibodies (CKM-B07, F12, D08, H09 and G01) against porcine creatine kinase (CK; EC 2.7.3.2) MM isoenzyme, which inhibit the enzymatic activity, were prepared. The hybridomas which produced monoclonal antibodies were screened by direct measurement of the inhibitory activity of their culture supernatant. Only two of them, however, were found to be measurable by an enzyme-linked immunosorbent assay with porcine CK-MM as an antigen. CKM-G01 inhibited 100% porcine CK-MM activity, while the others, 73-87%. On the other hand, only CKM-H09 inhibited porcine CK-BB activity (15%). CKM-F12 and D08 inhibited more than 50% CK-MB activity, whereas they did not inhibit CK-BB activity. The monoclonal antibodies were also tested for bovine, rabbit and human CK-MM. All the antibodies inhibited bovine and human CK-MM activity as well. In particular, CKM-G01 was found to exhibit more than 98% inhibition of all CK-MM activity tested, indicating that a common or very similar epitope which affects the activity is present on these enzymes. Admixing of CKM-B07 with other antibodies effected synergisms in inhibition, not only to porcine CK-MM activity but also to human CK-MM activity. A mixture of CK-B07 and G01 inhibited 100% human CK-MM activity, suggesting applicability of these monoclonal antibodies to clinical laboratory diagnosis.

Animals↗

Biological behaviour and morphological characteristics of a transplantable tumour (MM-KMY) derived from a malignant meningioma in an F344 rat.

A subcutaneously transplantable meningeal tumour (MM-KMY) was derived from a spontaneous malignant meningioma which developed in the cerebellar meninges of a female F344 rat. MM-KMY was subjected to 25 serial passages in syngeneic male and female rats. The transplants grew in 8 weeks into a nodule with an average diameter of 5.7 cm and average weight of 125.2 g. MM-KMY possessed large cysts containing fluid and necrotic tissue. Metastases frequently occurred in the lungs of MM-KMY-bearing rats. Histologically, both the original tumour and MM-KMY consisted of round to fusiform neoplastic cells of varying size, with nuclear pleomorphism. Mitotic figures occurred frequently. MM-KMY cells were positive for vimentin. Ultrastructurally, the cells showed desmosome-like structures, interdigitating processes and cytoplasmic intermediate filaments, suggesting an arachnoid cell origin. Abnormal accumulations of hyaline droplets in renal tubular epithelial cells were frequently observed in MM-KMY-bearing rats, suggesting overload of low molecular proteins in the renal tubules. The droplets gave a faint immunoreaction for lysozyme. The relation between the appearance of renal tubular hyaline droplets and the growth of MM-KMY remains to be determined. MM-KMY may prove useful for studying the biological behaviour and morphogenesis of meningeal tumours.

Animals↗

A novel method for prediction of long-term outcome of women with T1a, T1b, and 10-14 mm invasive breast cancers: a prospective study.

BACKGROUND: Women with small mammographically detected breast cancers generally have good long-term outcomes, but a few with T1a (1-5 mm) and T1b (6-10 mm) tumours will eventually die from breast cancer. We investigated whether women at high risk of breast-cancer death could be identified with mammographic criteria and differentiated from women with small cancers of the breast and good outcomes. METHODS: We prospectively applied mammographic classifications of tumour type to a consecutive series of 343 mammograms of invasive breast cancers of size 1-14 mm. Classifications were: stellate (spiculated) mass with no calcifications; circular or oval lesions with no calcifications; spiculated or circular lesions with non-casting-type calcifications; and casting-type calcifications. FINDINGS: 20-year survival for women with 1-14 mm invasive tumours with casting-type calcifications was 55%. 14% of 138 women with 1-9 mm tumours had casting-type calcifications on mammography, which accounted for 73% of all breast-cancer deaths (p<0.001). T1a, T1b, and 10-14 mm tumours with casting-type calcifications behaved as if they were larger lesions, since the rate of death was similar to that for women with advanced high-grade tumours. Most women who died were node-negative. The long-term survival of women who had tumours of 1-9 mm with no casting-type calcifications was about 95%. INTERPRETATION: Mammographic classification seemed to reliably predict good and bad long-term outcomes for survival in tumours of 14 mm or smaller, and especially for those smaller than 10 mm. The implications for therapy are substantial.

Breast Neoplasms↗

Use of 5-mm-diameter implants: Periotest values related to a clinical and radiographic evaluation.

A modified design of the original Brånemark implant consisting of a cp. Titanium 5.0-mm-diameter self-tapping implant threaded up to the marginal platform has been proposed for specific indications. From February 1992 to November 1995, a total of 185 machined screw implants (Nobel Biocare, Gothenburg, Sweden) were installed in 45 patients to withstand 58 prostheses. Of these, 91 were 3.75-mm diameter and 94 were 5.0-mm wide. Most of the implants were placed in type B and C bone quantity and type 2 and 3 bone quality. A retrospective evaluation with regard to indications, marginal bone remodelling, Periotest values (PTv) and survival rate is presented. PTv and radiographic measurements were made at abutment connection and repeated 3, 6 and 12 months later and thereafter every year. The follow-up ranged from 16 to 55 months (mean 32.9 months) post-loading. Three patients with 8 5.0-mm implants dropped-out of the study at different stages. Out of the wide implants, 1 was expelled during the healing period; 3 were found mobile at the abutment connection; 1 lost its osseointegration suddenly after 2 years of function; 4 belonging to 1 patient did not meet the success criteria due to continuous marginal bone loss. The cumulative success rate of 5.0-mm implants (CSR) after 1 year of function was 97.2% for upper jaws and 88.4% in mandibles, whereas the CSR in maxilla after 48 months was 97.2% and 83.4% in mandibles. The obtained PTv from 5.0-mm-wide fixtures in maxilla and mandibles were respectively 1.1 and 0.6 units lower than those obtained PTv for 3.75-mm-diameter implants in the same patients. The hypothesis that there are differences in the damping capacity of the bone surrounding a 5.0-mm-wide implant compared to the 3.75-mm-diameter implant is supported by the PTv results.

Adult↗

MM-derived exosomes promote M2 macrophage polarization and immunosuppressive microenvironment: therapeutic opportunities.

Multiple myeloma (MM) progression involves extensive immunosuppressive remodeling of the bone marrow microenvironment. In this study, we performed a comprehensive mass spectrometry-based proteomic analysis of exosomes derived from MM cells (MM-Exos), revealing that these exosomal proteins are predominantly enriched in pathways associated with immune regulation. We demonstrated that MM-Exos effectively drive macrophage polarization toward the M2 phenotype, thereby facilitating the establishment and maintenance of an immunosuppressive tumor microenvironment. Mechanistically, we identified the ERK1/2 signaling pathway as a critical mediator of MM-Exo-induced macrophage polarization. Importantly, we found that simvastatin, a widely used inhibitor of cholesterol biosynthesis, effectively impaired exosome secretion from MM cells and subsequently reduced M2 macrophage polarization. Collectively, our study reveals a novel mechanism of immune evasion in MM, in which MM-Exos promote the polarization of macrophages toward the M2 phenotype via ERK1/2 pathway activation. These findings underscore the therapeutic potential of targeting exosome-mediated intercellular communication within the MM bone marrow microenvironment to improve clinical outcomes.

Exosomes↗

Cloning and characterization of a novel variant (mM-rdgBbeta1) of mouse M-rdgBs, mammalian homologs of Drosophila retinal degeneration B gene proteins, and its mRNA localization in mouse brain in comparison with other M-rdgBs.

We report the cloning, characterization and localization in the brain of a novel isoform termed mM-rdgBbeta1 (mouse type of mammalian retinal degeneration Bbeta1 protein) in comparison with the localization of three known mammalian homologs (M-rdgBbeta, M-rdgB1, M-rdgB2). mM-rdgBbeta1 cDNA contains a sequence of 119 bp as a form of insertion in the open reading frame of the known mM-rdgBbeta, and encodes a protein of 269 amino acids with a calculated molecular mass of 31.7 kDa, different from the molecular mass of 38.3 kDa of mM-rdgBbeta. It also contains a phosphatidylinositol transfer protein (PITP)-like domain similar to the known three homologs, as well as D-rdgB. The recombinant mM-rdgBbeta1 protein shows the specific binding activity to phosphatidylinositol but not to other phospholipids. This novel molecule is localized not only in the cytoplasm but also in the nucleus, different from the cytoplasmic localization of mM-rdgBbeta. In in situ hybridization analysis, the gene expression for mM-rdgBbeta1 in the brain, though weak, is rather confined to the embryonic stage, different from wider expression of mM-rdgBbeta in the gray matters of pre- and post-natal brains. Taken together, mM-rdgBbeta1 is suggested to play a role in the phosphoinositide-mediated signaling in the neural development.

Amino Acid Sequence↗