Biomedical subjects

Takahiro Ogawa

Publications and source records attributed to Takahiro Ogawa.

At least 19 recordsLinked to original sources

PubMed2026

Genome analysis of the glycosphingolipid-producing green alga tetraselmis sp. NKG400013.

Microalgae are gaining attention as sustainable resources for the production of valuable compounds, including biofuels, pigments, and bioactive metabolites. To support metabolic engineering and genome editing approaches aimed at enhancing these traits, high-quality genome assemblies are essential; however, genomic information remains limited for many microalgal lineages. Tetraselmis sp. NKG400013 is a green alga known for high glycosphingolipid accumulation with distinctive structural features. Here, we report a draft genome assembly of this strain generated using PacBio HiFi sequencing and transcriptome-supported annotation. The assembled genome spans 423.7 Mbp, with 74.5% repetitive sequences and 15,322 predicted protein-coding genes. Comparative analyses across 11 green algal species revealed a positive correlation between genome sizes and repeat contents, indicating that transposable element expansion, particularly long terminal repeat retrotransposons, has substantially contributed to genome enlargement in Tetraselmis. Genome-wide functional annotation and ortholog inference identified core enzymes required for glycosylceramide biosynthesis. Both sphingolipid Δ4 and Δ8 desaturases were identified in Tetraselmis and their coexistence suggests an expanded capacity for long-chain base modification that may underlie its distinctive glycosphingolipid profile. These results establish a genomic framework for understanding the high glycosphingolipid-producing capacity of NKG400013 and provide insights into the evolutionary diversification of sphingolipid metabolism in green algae.

Chlorophyta↗

PubMed2006

Glycosaminoglycan degradation reduces mineralized tissue-titanium interfacial strength.

Although the localization of the proteoglycan/glycosaminoglycan (GAG) complex at the bone-titanium implant interface has been implied, the role of proteoglycans on the establishment of bone-titanium integration is unknown. The hypothesis to be tested was that proteoglycans play an important role in establishing bone-titanium interfacial adhesion. The objective of this study is to investigate the effect of proteoglycan knockdown by GAG enzymatic degradation on the interfacial strength between mineralized tissue and titanium having different surface topographies. Rat bone marrow-derived osteoblastic cells were cultured on either a machined titanium disk or an acid-etched titanium disk. At day 21 of culture, one of the three following GAG degradation enzymes was added into the culture; chondroitinase AC, chondroitinase B, or keratanase. After 3 days of incubation (at day 24 of culture), the laser spallation technique was applied to the samples in order to assess the tissue-titanium interfacial strength. In this technique, a laser-generated stress wave is used to separate the tissue-titanium interface, and the interfacial strength is determined interferometrically by recording the transient free surface velocity of the tissue. Mineralized tissue cultured on the acid-etched titanium showed 20-30% higher tissue interfacial strength than that cultured on the machined titanium (p < 0.0001). For both the machined and acid-etched surface cultures, administration of the enzyme reduced the interfacial strength by 25-30% compared with the untreated control cultures (p < 0.0001). There were no differences in the effect among the three different enzymes tested. A nanoindentation study revealed that the enzyme treatment did not affect the elastic modulus of the mineralized tissue. Scanning electron microscopic and energy dispersive spectroscopic analyses revealed less post-spallation tissue remnant on the titanium substrates when treated with the enzymes. The tissue remnant was greater in amount on the acid-etched surface than on the machined surface. The results suggest that there exists not only mechanical interlocking but also biological interfacial adhesion between the mineralized tissue and titanium, in which the proteoglycan/GAG complex is involved.

Animals↗

PubMed2006

Mutational analysis of the APC gene in cribriform-morula variant of papillary thyroid carcinoma.

INTRODUCTION: Familial adenomatous polyposis (FAP) is an inherited autosomal dominant syndrome caused by germline mutations in the adenomatous polyposis coli (APC) gene. Papillary thyroid cancer is one of the extracolonic manifestations of FAP. A characteristic histologic feature of this type of thyroid tumor is the cribriform-morula variant of papillary thyroid carcinoma (CMVPTC). METHODS: To investigate roles of the APC and beta-catenin genes in the development of CMVPTC, we examined germline and somatic mutations of these genes in a female patient with CMVPTC and FAP. The patient had undergone total colectomy at the age of 19 years and total thyroidectomy at age 25 years. RESULTS: Numerous tumors were disseminated in both lobes of the thyroid gland, and histopathologic examination revealed typical CMVPTC. DNA was extracted from peripheral blood leukocytes and 12 CMVPTC tumors, and exons 1-15 of the APC gene and exon 3 of the beta-catenin gene were examined. A germline mutation was detected in exon 13 of the APC gene, and this mutation generated a premature stop codon. Six somatic mutations (922delC, 1602delA, 1821delT, 1920delG, 2706del20, 2804insA) were found in the CMVPTC specimens. All mutations were truncating mutations in the N-terminus of the APC protein. Loss of heterozygosity was not observed in the remaining tumor tissues without somatic APC mutations. There were no mutations of the beta-catenin gene in peripheral blood leukocytes or 12 CMVPTC specimens. CONCLUSIONS: These results suggest that APC mutations play an important role in the development of CMVPTC and occur predominantly in the 5' side of the APC gene between codons 308 and 935.

Adenocarcinoma, Papillary↗

PubMed2005

Enhanced mineralized tissue adhesion to titanium over polystyrene assessed by the nano-scratch test.

The critical load determined by the scratch test is regarded to be a representative measure of coating adhesion in the field of engineering. This study aimed to evaluate the method for its usefulness for assessing the mineralized tissue-titanium interface strength. Osteoblastic cells derived from rat bone marrow were cultured on polystyrene, titanium-coated polystyrene, and titanium disks with either a machined or dual-acid etched surface. Nano-scratch testing was performed on mineralized tissue specimens at culture day 28. The scratch path was monitored by light microscopy until complete delamination of mineralized tissue from the substrate occurred, and the required force was recorded as the critical load. Energy-dispersive spectroscopic analysis was used to verify the delamination. The mean critical load values (+/- standard deviations) were as follows: polystyrene 31 mN (+/-1), titanium-coated polystyrene 67 mN (+/-4), machined titanium 76 mN (+/-4), DAE titanium 107 mN (+/-3), with statistical differences (P < 0.05; ANOVA). No elemental calcium and phosphorous were observed in the delaminated areas. The nano-scratch test applied to cultured mineralized tissue differentiated the critical load from various culture conditions: polystyrene vs. titanium; titanium with different surface topographies. Culturing mineralized tissue on titanium, especially on roughened surfaces, increased the tissue critical load. The nano-scratch test may be useful to evaluate mineralized tissue adhesion properties in titanium cultures.

Animals↗

PubMed2005

Osteoblasts generate harder, stiffer, and more delamination-resistant mineralized tissue on titanium than on polystyrene, associated with distinct tissue micro- and ultrastructure.

UNLABELLED: This study revealed that osteoblasts generate harder, stiffer, and more delamination-resistant mineralized tissue on titanium than on the tissue culture polystyrene, associated with modulated gene expression, uniform mineralization, well-crystallized interfacial calcium-phosphate layer, and intensive collagen deposition. Knowledge of this titanium-induced alteration of osteogenic potential leading to enhanced intrinsic biomechanical properties of mineralized tissue provides novel opportunities and implications for understanding and improving bone-titanium integration and engineering physiomechanically tolerant bone. INTRODUCTION: Bone-titanium integration is a biological phenomenon characterized by continuous generation and preservation of peri-implant bone and serves as endosseous anchors against endogenous and exogenous loading, of which mechanisms are poorly understood. This study determines the intrinsic biomechanical properties and interfacial strength of cultured mineralized tissue on titanium and characterizes the tissue structure as possible contributing factors in biomechanical modulation. MATERIALS AND METHODS: Rat bone marrow-derived osteoblastic cells were cultured either on a tissue culture-grade polystyrene dish or titanium-coated polystyrene dish having comparable surface topography. Nano-indentation and nano-scratch tests were undertaken on mineralized tissues cultured for 28 days to evaluate its hardness, elastic modulus, and critical load (force required to delaminate tissue). Gene expression was analyzed using RT-PCR. The tissue structural properties were examined by scanning electron microscopy (SEM), collagen colorimetry and localization with Sirius red stain, mineral quantification, and localization with von Kossa stain and transmission electron microscopy (TEM). RESULTS: Hardness and elastic modulus of mineralized tissue on titanium were three and two times greater, respectively, than those on the polystyrene. Three times greater force was required to delaminate the tissue on titanium than that on the polystyrene. SEM of the polystyrene culture displayed a porous structure consisting of fibrous and globular components, whereas the titanium tissue culture appeared to be uniformly solid. Cell proliferation was remarkably reduced on titanium. Microscopic observations revealed that the mineralized tissue on titanium was composed of uniform collagen-supported mineralization from the titanium interface to the outer surface, with intensive collagen deposition at tissue-titanium interface. In contrast, tissue on the polystyrene was characterized by collagen-deficient mineralization at the polystyrene interface and calcium-free collagenous matrix formation in the outer tissue area. Such characteristic microstructure of titanium-associated tissue was corresponded with upregulated gene expression of collagen I and III, osteopontin, and osteocalcin mRNA. Cross-sectional TEM revealed the apposition of a high-contrast and well-crystallized calcium phosphate layer at the titanium interface but not at the polystyrene interface. CONCLUSIONS: Culturing osteoblasts on titanium, compared with polystyrene, enhances the hardness, elastic modulus, and interfacial strength of mineralized tissue to a higher degree. Titanium per se possesses an ability to alter cellular phenotypes and tissue micro- and ultrastructure that result in enhanced intrinsic biomechanical properties of mineralized tissue.

Animals↗

PubMed2005

Weekly paclitaxel in the treatment of advanced or metastatic breast cancer previously treated or not treated with docetaxel: a phase II study.

BACKGROUND: Paclitaxel has been approved for 3-weekly administration in Japan. Recent reports suggest that weekly paclitaxel can achieve a higher tumor response and lower toxicity. METHODS: This study was designed to investigate the usefulness and tolerability of weekly paclitaxel by 1-hour infusion in patients with metastatic breast cancer who were previously treated with docetaxel or other anticancer agents. RESULTS: Thirty-five patients were enrolled. The overall response rate was 41.2% (14/34, 95% confidence interval: 24.6-59.3%). The median time to progression and the median survival time were 218.5 and 624 days, respectively. One patient developed dyspnea, probably induced by a hypersensitivity reaction. The most common hematological toxicities were leukopenia and neutropenia, although no patients developed grade 4 leukopenia or neutropenia and G-CSF support was not required. CONCLUSIONS: Weekly paclitaxel could be safely administered and achieved a relatively high response rate. Weekly paclitaxel would be a good candidate second-line therapy for recurrent or advanced breast cancer.

Adult↗

PubMed2005

Enhanced intrinsic biomechanical properties of osteoblastic mineralized tissue on roughened titanium surface.

The biological mechanisms underlying bone-titanium integration and biomechanical properties of the integrated bone are poorly understood. This study assesses intrinsic biomechanical properties of mineralized tissue cultured on titanium having different surface topographies. The osteoblastic phenotypes associated with mineral deposition and collagen synthesis underlying the biomechanical modulation are also reported. Rat bone marrow-derived osteoblastic cells were cultured either on the machined titanium disc or acid-etched titanium disc. Nano-indentation study of day 28 culture revealed that the mineralized tissue on the acid-etched surface shows 3-3.5 times greater hardness than that on the machined surface (p < 0.01). Elastic modulus of the mineralized tissue was also 2.5-3 times greater on the acid-etched surface than on the machined surface (p < 0.01). After 28 days of culture, mineralized nodule area was significantly lower on the acid-etched surface than on the machined surface (p = 0.0105), while total calcium deposition did not differ between the two surfaces, indicating denser mineral deposition on the acid-etched surface. Osteopontin and osteocalcin gene expressions assayed by the reverse transcriptase-polymerase chain reaction were upregulated in the acid-etched titanium culture. Collagen synthesis measured by Sirius red stain-based colorimetry was 1.5-10 times higher on the acid-etched surface than on the machined surface in the initial culture period of day 1 to day 14 (p < 0.0001). The amount of collagen synthesis corresponded with the enhanced gene expression of prolyl 4-hydroxylase, a key enzyme for post-translational modification of collagen chains. Scanning electron microscopic images revealed that tissue cultured on the acid-etched titanium exhibited plate-like, compact surface morphology, while the tissue on the machined titanium appeared porous and was covered by fibrous and punctate structures. We conclude that culturing osteoblasts on rougher titanium surfaces enhances hardness and elastic modulus of the mineralized tissue, associated with condensed mineralization, accelerated collagen synthesis, and upregulated expression of selected bone-related genes.

Animals↗

PubMed2005

Sequential changes in plasma intact and whole parathyroid hormone levels during parathyroidectomy for secondary hyperparathyroidism.

Most commercial assays for intact parathyroid hormone (iPTH) cross-react with non-PTH1-84 fragments (likely to be PTH7-84). We aimed to evaluate a whole PTH assay that measured only PTH1-84 by comparing it with an assay measuring iPTH levels during parathyroidectomy in secondary hyperparathyroidism (HPT). Twenty-eight patients with secondary HPT who underwent total parathyroidectomy with autotransplantation served as subjects. Blood samples for postoperative assay were drawn after anesthesia; immediately prior to excision of the last parathyroid gland; and at 5, 10, and 15 minutes after excision. The PTH7-84 level was calculated by subtracting the whole PTH value from the iPTH value. Plasma whole PTH decreased more rapidly than iPTH after parathyroidectomy (p < 0.0001). PTH levels that decreased by 50% or more from levels prior to excision to 10 minutes after excision were used to predict successful parathyroidectomy; decreases in whole PTH substantiated curative surgery for all patients without introducing false-positive and false-negative results. iPTH levels decreased by at least 50% in only 16 patients at 10 minutes after excision without false-positive results. Out of 11 cases in which iPTH decreased less than 50%, two were true-negatives and nine were false-negatives. Decreases in whole PTH levels more accurately reflect surgical outcome than do decreases in iPTH levels during parathyroidectomy in secondary HPT patients. Even though the quick iPTH assay is used infrequently during surgery for secondary HPT, our results suggest that a quick whole PTH assay may be more useful than the iPTH assay currently used in parathyroidectomy procedures for secondary HPT.

Female↗

PubMed2005

Intraoperative parathyroid hormone assay in patients with Graves' disease for prediction of postoperative tetany.

We measured intraoperative parathyroid hormone (IOPTH) levels before and after thyroidectomy in a large group of patients to test whether changes in IOPTH can predict postoperative tetany. Subjects were 111 consecutive patients (94 females and 17 males) with Graves' disease undergoing subtotal thyroidectomy. Blood samples for IOPTH assay were obtained after anesthesia (basal) and following skin closure (postoperative). Data were compared between patients who developed tetany (n = 9) and those who did not (n = 102). There was no significant difference in sex, age, period of antithyroid drug administration, or the weight of the thyroid between the two groups. The preoperative serum calcium level was significantly lower (p < 0.05) and the basal IOPTH significantly higher (p < 0.05) in the tetany group than in the non-tetany group. The IOPTH level was significantly lower (p < 0.005) and the average percent decrease in IOPTH levels was higher (p < 0.001) in the tetany group than in the non-tetany group. A decrease in IOPTH of more than 70% was shown to be 78% sensitive, 94% specific, and 93% accurate, and it has 78% positive predictive value and 94% negative predictive value for the development of tetany. Our study shows that a postoperative decrease of IOPTH level is the most predictive of postoperative tetany of the clinical risk factors investigated. We recommend IOPTH measurement as an adjunct to postoperative management of patients with Graves' disease to assist in preventing hypocalcemia and determining the earliest time for safe discharge.

Adolescent↗

PubMed2005

Reelevation of parathyroid hormone level after parathyroidectomy in patients with primary hyperparathyroidism: importance of decreased renal parathyroid hormone sensitivity.

BACKGROUND: We hypothesized that impaired peripheral sensitivity to parathyroid hormone (PTH) may play a role in reelevation of PTH after successful operation for primary hyperparathyroidism (pHPT). METHODS: Factors affecting reelevation of PTH were determined in 90 patients who underwent parathyroidectomy for pHPT. PTH/nephrogenous cyclic adenosine monophosphate ratio, as an index of renal resistance to PTH, was examined in relation to factors shown to influence reelevation of PTH. RESULTS: Serum PTH levels were elevated above the upper limit of normal in 23 patients (26%) at 1 week and in 39 patients (43%) at 1 month after parathyroidectomy. These 39 normocalcemic patients with elevated serum PTH at 1 month after parathyroidectomy had a higher preoperative serum level of PTH and lower serum phosphate and 25-hydroxyvitamin D (25OHD) concentrations than those with normal PTH (n = 59). Elevated PTH and low 25OHD were shown by multivariate analysis to be significant predictors of reelevation of PTH. Renal resistance to PTH was higher in patients with vitamin D deficiency or renal insufficiency than in patients with normal serum vitamin D concentrations or normal renal function, and it increased according to increases in levels of PTH. CONCLUSIONS: The mechanism of PTH reelevation in patients with pHPT after successful parathyroidectomy appears to be renal resistance to PTH.

Adenoma↗

PubMed2005

Timolol LA: a double-masked, active-controlled, randomized, crossover, comfort, ocular safety, and systemic bioavailability study in healthy volunteers.

PURPOSE: A new formulation of timolol with sorbic acid, timolol-LA (TLA) (Istaloldagger), has been developed which increases its ocular bioavailability. In the present study, we desired to evaluate the ocular comfort and systemic bioavailability of TLA in healthy volunteers in comparison to standard timolol maleate ophthalmic solution (TIM). METHODS: This study was a randomized, double-masked, active-controlled, crossover evaluation of 0.5% TLA and 0.5% TIM, bid, in 12 normal healthy volunteers. Visits were at Days 0, 1, 2, 4 and 8 in each period, and there was a minimum 7 day interperiod washout. RESULTS: At all three post-dosing evaluation times (Day 1: Peak, Day 8: Trough, and Day 8: Peak), the 95% confidence interval for the difference between TLA and TIM was not more than 0.37 ng/mL. After administration of TLA, there was a greater incidence of burning/stinging and tearing, but not foreign body sensation, relative to TIM. In general, most symptoms were mild in intensity, and no subject discontinued treatment due to ocular discomfort. Both treatments decreased IOP to a similar level. CONCLUSION: TLA was relatively comfortable, with a safety profile consistent with further clinical development, and, with bid dosing (exaggerated [2X] that anticipated for clinical use), had a systemic bioavailability similar to that of TIM 0.5%, bid. The incidence of burning and stinging was higher with TLA than with TIM, although reports were mild in severity and did not result in any patient discontin uations. Although the results are of interest, further evaluation in a larger trial may be warranted.

Adrenergic beta-Antagonists↗

PubMed2005

Significance of an insular component in follicular thyroid carcinoma with distant metastasis at initial presentation.

Risk factors for distant metastasis were studied in 82 patients with follicular thyroid carcinoma (FTC). Metastases to either the lung or bone existing at the time of presentation were confirmed by I-131 radio-iodine uptake in 10 patients. FTC with an insular component was found in eight patients. Univariate analysis of 14 possible risk factors showed 7 to be statistically significant: insular component, poorly differentiated carcinoma, trabecular component, serum thyroglobulin level before surgery, patient age at the time of presentation, solid component, and vascular invasion (ranked by p values). After further analysis of the interrelation of the factors and of the logistic regression curves, we concluded that presence of an insular component and patient age were the only independent risk factors. Distant metastasis was not detected in any of the 27 patients < or = 49 yr old. Among the 55 older patients (> or = 50 yr old), 5 of the 49 (10%) without an insular component and 5 of the 6 (83%) with an insular component had distant metastasis. The remaining older patient with an insular component but without distant metastasis showed a gradual increase in thyroglobulin levels after total thyroidectomy.

Adenocarcinoma, Follicular↗

PubMed2004

Efficacy and cytotoxicity of cationic-agent-mediated nonviral gene transfer into osteoblasts.

Ex vivo gene transfer into osteoblastic cells is an advantageous strategy for bone tissue engineering. This study investigated the efficacy and cytotoxicity of in vitro cationic-agent-mediated nonviral gene transfer into osteoblasts. Various cationic agents, lipid, gelatin, and polyethylenimine (PEI) were tested. Each was formulated in various concentrations to form a complex with plasmid DNA encoding red fluorescent protein. The cationic agent/DNA complexes were transfected into human fetal osteoblastic cell line and rat bone-marrow-derived primary osteoblasts, as well as NIH 3T3 fibroblast controls. Rat primary osteoblasts were transfected more with cationic lipid and PEI agents than with gelatin carrier, yielding transfection efficacy up to 18.1% and 12.7 %, respectively. In contrast, human fetal osteoblastic cell line was transfected more with cationic lipid and gelatin than with PEI. There was a positive correlation between the lipid and PEI doses and cytotoxicity. When the lipid and PEI were used to transfect the rat primary osteoblasts in a dose that yielded the highest transfection efficacy, cell survival rates decreased as low as 40%. When their transfection efficacies into primary osteoblasts were compromised at two thirds of the highest value, that is, 12.6% and 8.3% for the lipid and PEI, respectively, the cell survival rate was nearly 80%. Cationic gelatin was associated with cell survival rates over 60 % in any cell type, regardless of the doses tested. These results suggest that different types of osteoblastic cells may possess different ability to the uptake and expression of cationic-agent-bound DNA. There seemed to be agent-specific threshold doses that dropped the cell survival rate. Cationic-agent-mediated nonviral gene transfer into osteoblastic cells may be successful when the agent- and dose-dependent transfection efficacy and cytotoxicity are optimized.

Animals↗

PubMed2004

Detection of asymptomatic differentiated thyroid carcinoma by neck ultrasonographic screening for familial nonmedullary thyroid carcinoma.

Mass screening for the purpose of detecting thyroid cancer at its earliest stage may not be recommended at the present time, but screening focused on certain risk groups is advocated. Familial nonmedullary thyroid carcinoma (FNMTC) is a distinct clinical entity with a high incidence of multifocality and association with multiple benign nodules. FNMTC patients have shorter disease-free survival than do sporadic disease patients because of frequent locoregional recurrence. Screening by neck ultrasonography was performed for symptom-free family members of patients with FNMTC. A total of 149 subjects representing 53 FNMTC families were examined in this study. The average age of the patients was 41.0+/-19.0 years (range 3-76 years) with a female/male ratio of 104:45. At least one thyroid nodule was found in 77 (51.7%) of the 149 patients. Surgery was performed in 18 patients, and thyroid cancer was discovered in 15 of them (10.1%; 14 women, 1 man; 32-61 years of age). Papillary thyroid cancer (PTC) was found in 14 and follicular thyroid cancer combined with PTC in 1. The tumors averaged 9.1+/-5.4 mm (3-21 mm) in greatest diameter. Intraglandular metastases were found in 7 (47%) of the 15 patients with thyroid cancer. Lymph node metastases were found in 6 (43%). Ultrasonographic screening for FNMTC family members may enable the discovery of asymptomatic thyroid cancer. Because of the high incidence of intraglandular and lymph node metastases, we recommend screening with ultrasonography for early detection in family members of patients with FNMTC.

Adolescent↗

PubMed2004

Crank-shaped sternotomy for upper mediastinal lymph node dissection in patients with differentiated thyroid cancer.

We describe our modification of the reversed T-shaped sternotomy. The conventional technique consists of a limited upper sternotomy with transverse division of the sternum. Our modification involves shifting the transverse division lines one costal space between the right and left sides for perfect apposition of the divided upper and lower sternum. This technique can be used for patients with thyroid cancer and mediastinal lymph node metastasis and for those with a mediastinal tumor or certain cardiac disorders.

Female↗

PubMed2004

Comparison of parathyroid hormone levels from the intact and whole parathyroid hormone assays after parathyroidectomy for primary and secondary hyperparathyroidism.

BACKGROUND: Most commercial intact parathyroid hormone (intact PTH) assays cross-react with non-(1-84) PTH (likely 7-84 PTH). Using a whole-molecule PTH (whole PTH) assay that specifically measured only 1-84 PTH, we compared the kinetics of whole PTH and intact PTH after parathyroidectomy in patients with primary hyperparathyroidism (HPT) and secondary HPT. METHODS: This study comprised 74 patients with primary HPT caused by a single adenoma and 18 patients with secondary HPT who underwent parathyroidectomy. Blood samples were drawn after anesthesia, just before excision of a single adenoma in primary HPT, and just before excision of the last parathyroid gland in secondary HPT, and at 5, 10, and 15 minutes after excision. The 7-84 PTH level was calculated by subtracting the whole PTH value from the intact PTH value. RESULTS: There was a difference between the percentage of 7-84 PTH/intact PTH in plasma samples from patients with primary HPT and secondary HPT (28%+/-12% vs 35%+/-9%; P<.05). Plasma whole PTH decreased more rapidly than intact PTH after parathyroidectomy in patients in both the primary HPT (P<.0001) and secondary HPT groups (P<.0001). Decline of intact PTH was slower in patients with secondary HPT than in patients with primary HPT; however, there was no significant difference in the decline of whole PTH between the 2 groups. CONCLUSIONS: The quick intact PTH assay is not used frequently during surgery in patients with secondary HPT; however, our results suggest that a quick whole PTH assay may be a more useful adjunct to parathyroidectomy in both secondary HPT and primary HPT.

Humans↗

PubMed2004

A 12-month, multicenter, randomized, double-masked, parallel-group comparison of timolol-LA once daily and timolol maleate ophthalmic solution twice daily in the treatment of adults with glaucoma or ocular hypertension.

BACKGROUND: Timolol maleate, a nonselective beta-adrenoceptor antagonist applied topically to the eye as a solution, is well known for its ocular hypotensive efficacy. A gellan formulation of timolol maleate is given once daily and has been shown to be as effective as timolol maleate solution, but is associated with ocular symptoms that may limit its utility. A new timolol maleate solution has been formulated that contains potassium sorbate (timolol-LA [TLA; Istalol(R)]) to enhance the ocular bioavailability of timolol instilled into the eye, as well as half the benzalkonium chloride preservative found in timolol maleate. OBJECTIVE: The objective of this trial was to assess the ocular hypotensive efficacy and safety profile of TLA 0.5% solution once daily with those of timolol maleate ophthalmic solution (TIM) 0.5% twice daily in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: This multicenter, prospective, randomized, double-masked, parallel-group clinical trial was conducted at 21 participating private practices across the United States. Patients aged > or =18 years with OAG or OHT in 1 or both eyes and an unmedicated intraocular pressure (IOP) of > or =22 mm Hg were randomized to receive either TLA once daily or TIM twice daily bilaterally for 12 months. The primary outcome measure was IOP (95% CIs) on treatment difference at each visit (ie, equivalence analysis). The safety profile was assessed based on biomicroscopic and ophthalmoscopic examination and patient symptoms. RESULTS: A total of 332 patients (203 women, 129 men; mean [SEM] age, 64.6 [11.8] years [range, 29-92 years]) entered the study. Of these, 290 patients (87.3%) completed it. At none of the visits did the 95% CIs for between-treatment comparisons exceed 1.5 mm Hg and, at most of the visits, these intervals did not exceed 1.0 mm Hg. Mean baseline IOP was approximately 25 mm Hg in both groups. IOP was reduced at all posttreatment visits to 18 to 19 mm Hg at peak and to approximately 19 to 20 mm Hg at trough drug level in both treatment groups. Mean reductions from baseline were 6 to 7 mm Hg at peak and 5 to 6 mm Hg at trough (25.5%-28.7% and 20.8%-24.7%, respectively). Seventeen patients (5.1%) withdrew due to adverse events (AEs) (10 patients [6.0%] and 7 patients [4.2%] in the TLA and TIM groups, respectively). Based on biomicroscopic and ophthalmoscopic examination and volunteered symptoms, the safety profile was similar between the 2 treatments, except for burning and stinging on instillation, with an incidence of 41.6% in the TLA group and 22.9% in the TIM group (P = 0.001). Nearly all cases of burning and stinging were mild (94.2% [65 events] with TLA and 90.0% [36 events] with TIM), and none of the patients discontinued treatment due to this AE. CONCLUSIONS: TLA solution, a nonselective beta-adrenoceptor antagonist, given once daily in the morning, was found to be statistically equivalent in ocular hypotensive efficacy (as defined a priori) compared with TIM, given twice daily, and with an acceptable safety profile in this study population of adult patients.

Adult↗

PubMed2003

Oral fibroblast expression of wound-inducible transcript 3.0 (wit3.0) accelerates the collagen gel contraction in vitro.

Wounds of the oral mucosa show faster closure with less scar formation than skin wounds in other areas. A differentially expressed cDNA, wound-inducible transcript 3.0 (wit3.0), was isolated from oral mucosal wound in rats (Sukotjo, C., Abanmy, A. A., Ogawa, T., and Nishimura, I. (2002) J. Dent. Res. 81, 229-235). The purpose of this study was to characterize the wit3.0 gene structure and the function of its deduced peptide. Human and rat genome databases revealed that the gene for wit3.0 was located in human chromosome 12p11.23 and rat chromosome 4q44. Its human and rat gene structures were well conserved, composed of 7 exons spread over 20 kb. Exon 5 was alternatively spliced generating two transcripts encoding deduced peptides of 215 and 253 amino acids (wit3.0 alpha and wit3.0 beta, respectively). The protein families data base of alignments (Pfam) analysis suggested the wit3.0 peptide sequence shared similarity with a portion of the myosin II coiled-coil domain consensus sequence. Fibroblasts isolated from the rat oral wound up-regulated wit3.0 expression and exhibited greater ability to contract collagen gel in vitro than fibroblasts isolated from untreated oral mucosa/gingiva. NIH3T3 and rat oral fibroblasts transfected with expression vector containing the coding sequences of wit3.0 alpha or wit3.0 beta increased in vitro collagen gel contraction. When treated with TGF beta-1, NIH3T3 fibroblast expression of wit3.0 showed no significant change, whereas alpha smooth muscle actin was increased in a dose-dependent manner. These data suggest that there may be a novel wound healing pathway involving wit3.0 underlying the favorable early wound closure characteristics of oral mucosa.

Actins↗