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Biomedical subjects

An Liu

Publications and source records attributed to An Liu.

At least 19 recordsLinked to original sources

Targeting the bile acid receptor TGR5 with Gentiopicroside to activate Nrf2 antioxidant signaling and mitigate Parkinson's disease in an MPTP mouse model.

INTRODUCTION: Parkinson's disease (PD) is a common neurodegenerative disorder characterized by classical symptoms including bradykinesia, rest tremor and rigidity. Oxidative stress and mitochondrial dysfunction are recognized as pivotal factors in PD progression. Gentiopicroside (GPS), a secoiridoid derived from Gentiana manshurica Kitagawa, exhibits antioxidant and mitophagy induction properties. Nonetheless, the effects and mechanisms by which GPS mitigates neurodegeneration in PD remain to be thoroughly elucidated. OBJECTIVES: The goal of this study was to investigate the neuroprotective effects and mechanisms of GPS in PD models. METHODS: We established the MPTP/MPP+-induced PD models to measure the neuroprotection of GPS. Transcriptomic analysis, oxidative biochemical kits, western blot and cell immunofluorescence were conducted to elucidate the fundamental mechanisms at play. Subsequently, the targeting and activation of the transmembrane G protein-coupled receptor-5 (TGR5) by GPS were measured by molecular docking, cellular thermal shift assay, microscale thermophoresis (MST) and cyclic adenosine monophosphate (cAMP) quantitation. Finally, we verified whether the neuroprotective and antioxidant effects of GPS were dependent on TGR5 by using specific small interfering RNA (siRNA), pharmacological antagonist and knockout mice. RESULTS: GPS significantly attenuated dopaminergic (DAergic) neuron loss and restored motor function in the MPTP-induced PD mouse model. Whole-genome RNA sequencing and subsequent mechanistic investigations revealed that GPS enhanced the expression and facilitated nuclear entry of factor erythroid-related 2-factor 2 (Nrf2), and reduced oxidative stress and mitochondrial dysfunction stimulated by neurotoxin. Additionally, GPS could target TGR5 and prevent its downregulation in PD model. TGR5's silencing or inhibition weakened the neuroprotective effect of GPS and blocked GPS-mediated activation of Nrf2 antioxidant signaling in PD model. Moreover, the therapeutic effect of GPS in mitigating motor deficits and neurodegeneration was also abolished in Tgr5 knockout mice. CONCLUSION: These findings collectively indicated that GPS targeted TGR5 to activate Nrf2 antioxidant signaling and ultimately ameliorated the pathological progression of PD.

Animals↗

Results of a randomized, double-blind, vehicle-controlled efficacy trial of pimecrolimus cream 1% for the treatment of moderate to severe facial seborrheic dermatitis.

BACKGROUND: Seborrheic dermatitis is commonly treated with anti-inflammatory products, including topical corticosteroids. Pimecrolimus cream 1% also exerts anti-inflammatory activity by inhibiting T-cell cytokine production. OBJECTIVE: We sought to compare the efficacy and safety of twice-daily pimecrolimus for treatment of moderate to severe facial seborrheic dermatitis. METHODS: This double-blind, vehicle-controlled, 4-week trial randomized patients with seborrheic dermatitis to pimecrolimus or vehicle (1:1). Clinical assessments (erythema [0-3] and scaling [0-3] combined for a total area score [0-6]) were performed at weeks 0, 2, and 4. Inclusion criteria included total area score 4 or greater and erythema 2 or greater. The prespecified primary variable, change from baseline in total area score at week 4, was analyzed using a two-sample t test for intent-to-treat and per protocol populations. RESULTS: In all, 96 adults of mean age 59.6 years, 88.5% male, were randomized (n = 47 pimecrolimus; 49 vehicle). At week 4, the mean change from baseline in total area score was 3.7 versus 3.3 for pimecrolimus and vehicle groups, respectively (intent-to-treat: P = .1913; 95% confidence interval (CI) for difference [-0.195, 0.961]). Per protocol analysis (n = 41 pimecrolimus; 46 vehicle) indicated a significant difference between groups (mean change 3.9 pimecrolimus vs 3.2 vehicle; P = .0156; CI [0.129, 1.197]). The superiority of pimecrolimus was observed as early as week 2 (intent-to-treat: P = .0062; CI [0.132, 0.777]; per protocol: P = .0012; CI [0.410, 1.593]). No drug-related serious adverse events occurred. The most frequent drug-related adverse events were local, mild, and transient (pimecrolimus = 26%; vehicle = 12%). LIMITATIONS: Generalizability is limited by the elderly male study population. CONCLUSION: This study suggests that pimecrolimus cream 1% is an effective and well-tolerated treatment for moderate to severe facial seborrheic dermatitis.

Adult↗

Dosimetric comparison of helical tomotherapy treatment and step-and-shoot intensity-modulated radiotherapy of retroperitoneal sarcoma.

PURPOSE: To compare step-and-shoot intensity-modulated radiation therapy (SAS-IMRT) and helical tomotherapy (Tomo) dosimetry plans for patients who have received adjuvant radiation therapy for retroperitoneal sarcomas (RSTS). METHODS AND MATERIALS: A retrospective review was performed for seven patients who received either SAS-IMRT or Tomo as adjuvant radiation therapy for RSTS. In each case, a treatment plan of the other modality was generated so that SAS-IMRT and Tomo could be compared. RESULTS: The average percentage of clinical target volume (CTV) that received less than the prescription dose was 1.4% for Tomo compared to 3.8% for SAS-IMRT. Both SAS-IMRT and Tomo plans provided comparable and significant reductions in volume of small bowel receiving greater than 45 Gy compared to simple opposing standard radiation fields. For the ipsilateral kidney, Tomo significantly reduced the volume of kidney that received at least 15 Gy (average 22% for Tomo vs. 56% for SAS-IMRT). CONCLUSION: Both SAS-IMRT and Tomo can encompass the large CTV often required for patients with RSTS, although Tomo provides superior dose uniformity. Both SAS-IMRT and Tomo can minimize the volume of small bowel receiving greater than 45 Gy. Tomo was superior to SAS-IMRT in minimizing the volume of ipsilateral kidney irradiated to greater than 15 Gy when the CTV is adjacent to a kidney. Dose escalation and target margin expansion may thus become realistic possibilities.

Adult↗

Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma.

PURPOSE: TM-601 binds to malignant brain tumor cells with high affinity and does not seem to bind to normal brain tissue. Preclinical studies suggest that iodine-131 (131I) -TM-601 may be an effective targeted therapy for the treatment of glioma. We evaluated the safety, biodistribution, and dosimetry of intracavitary-administered 131I-TM-601 in patients with recurrent glioma. PATIENTS AND METHODS: Eighteen adult patients (17 with glioblastoma multiforme and one with anaplastic astrocytoma) with histologically documented recurrent glioma and a Karnofsky performance status of > or = 60% who were eligible for cytoreductive craniotomy were enrolled. An intracavitary catheter with subcutaneous reservoir was placed in the tumor cavity during surgery. Two weeks after surgery, patients received a single dose of 131I-TM-601 from one of three dosing panels (0.25, 0.50, or 1.0 mg of TM-601), each labeled with 10 mCi of 131I. RESULTS: Intracavitary administration was well tolerated, with no dose-limiting toxicities observed. 131I-TM-601 bound to the tumor periphery and demonstrated long-term retention at the tumor with minimal uptake in any other organ system. Nonbound peptide was eliminated from the body within 24 to 48 hours. Only minor adverse events were reported during the 22 days after administration. At day 180, four patients had radiographic stable disease, and one had a partial response. Two of these patients further improved and were without evidence of disease for more than 30 months. CONCLUSION: A single dose of 10 mCi 131I-TM-601 was well tolerated for 0.25 to 1.0 mg TM-601 and may have an antitumoral effect. Dosimetry and biodistribution from this first trial suggest that phase II studies of 131I-TM-601 are indicated.

Adult↗

Dosimetric comparisons of helical tomotherapy treatment plans and step-and-shoot intensity-modulated radiosurgery treatment plans in intracranial stereotactic radiosurgery.

PURPOSE: To evaluate dose conformity, dose homogeneity, and dose gradient in helical tomotherapy treatment plans for stereotactic radiosurgery, and compare results with step-and-shoot intensity-modulated radiosurgery (IMRS) treatment plans. METHODS AND MATERIALS: Sixteen patients were selected with a mean tumor size of 14.65 +/- 11.2 cm3. Original step-and-shoot IMRS treatment plans used coplanar fields because of the constraint of the beam stopper. Retrospective step-and-shoot IMRS plans were generated using noncoplanar fields. Helical tomotherapy treatment plans were generated using the tomotherapy planning station. Dose conformity index, dose gradient score index, and homogeneity index were used in plan intercomparisons. RESULTS: Noncoplanar IMRS plans increased dose conformity and dose gradient, but not dose homogeneity, compared with coplanar IMRS plans. Tomotherapy plans increased dose conformity and dose gradient, yet increased dose heterogeneity compared with noncoplanar IMRS plans. The average dose conformity index values were 1.53 +/- 0.38, 1.35 +/- 0.15, and 1.26 +/- 0.10 in coplanar IMRS, noncoplanar IMRS, and tomotherapy plans, respectively. The average dose homogeneity index values were 1.15 +/- 0.05, 1.13 +/- 0.04, and 1.18 +/- 0.09 in coplanar IMRS, noncoplanar IMRS, and tomotherapy plans, respectively. The mean dose gradient score index values were 1.37 +/- 19.08, 22.32 +/- 19.20, and 43.28 +/- 13.78 in coplanar IMRS, noncoplanar IMRS, and tomotherapy plans, respectively. The mean treatment time in tomotherapy was 42 +/- 16 min. CONCLUSIONS: We were able to achieve better dose conformity and dose gradient in tomotherapy plans compared with step-and-shoot IMRS plans for intracranial stereotactic radiosurgery. However, tomotherapy treatment time was significantly larger than that in step-and-shoot IMRS.

Algorithms↗

Long term clinical trials: how much information do participants retain from the informed consent process?

Previous studies report mixed results about how much information study participants actually can read, understand and retain after completing the informed consent process; fewer studies have examined disparities in the retention and recall of information by patient factors, such as age, education, and race. Not retaining or being able to recall information from the informed consent process has potentially important ethical and legal implications and consequences for research quality and integrity, especially when found in populations that commonly are underserved or underrepresented in clinical trials. To determine how much basic knowledge participants finishing a five-year, multi-center, double-blinded randomized, placebo-controlled clinical trial had about the study, participants (n=1,789) were asked at their final follow-up visit three multiple-choice questions: (1) the study's purpose; (2) the name of the medication under investigation; (3) the main side effect of the medication. The associations between knowledge of these fundamental details and participant social and demographic factors were investigated. A majority of participants correctly recalled the study's purpose (64.7%) and medication (79.6%), but few correctly reported the main side effect (31.1%). In spite of relatively high recall for study purpose and medication, disparities by age, education and race exist. Increasing age was significantly associated with higher odds of incorrectly recalling both the study purpose and the name of the study medication. Likewise those with less than a high school education were more likely to incorrectly identify the study's purpose and the name of the study medication. Black and other non-white race or ethnic groups were more than two and a half times as likely to incorrectly identify the study's purpose. These findings suggest that even the most basic information may not be understood or retained by important subgroups of patients enrolled in clinical trials. Implementing effective strategies, such as additional time and effort for consent or repetition of study information, may be necessary in order to assure ethical and valid consent.

Age Factors↗

Targeted total marrow irradiation using three-dimensional image-guided tomographic intensity-modulated radiation therapy: an alternative to standard total body irradiation.

Total body irradiation (TBI) is an important part of bone marrow transplantation conditioning regimens. In TBI, dose escalation is difficult, because of associated normal organ toxicities. A method to deliver a more targeted dose of TBI preferentially to sites of greatest tumor burden is needed to reduce the dose to normal organs, reduce toxicities, and permit dose escalation. The purpose of this study was to evaluate, through a dosimetric analysis, the potential advantages and feasibility of selectively delivering targeted myeloablative doses of radiation to bone and marrow using a recently developed image-guided tomographic intensity-modulated radiation therapy delivery system (helical tomotherapy). Whole-body computed tomography datasets from 3 patients, age 5, 20, and 53 years, were used for treatment planning studies to evaluate 2 targeted TBI strategies: total marrow irradiation (TMI), in which the target region was defined as the skeletal bone, and total marrow and lymphoid irradiation (TMLI), in which the target regions were defined as bone, major lymph node chains, liver, spleen, and sanctuary sites, such as brain. Organ doses and dose distributions were compared with those in conventional TBI. A 1.7- to 7.5-fold reduction in median organ doses was observed with TMI and TMLI compared with conventional TBI. With this more targeted approach, a dose-volume histogram analysis predicted the potential to escalate the dose to bone (and containing marrow) up to 20 Gy, while maintaining doses to normal organs at lower levels than in conventional TBI to 12 Gy. Results were similar for the adult and pediatric patients, indicating that this form of targeted TBI will be applicable to most patients regardless of frame size. TMI to 10 Gy was delivered as part of a tandem transplant regimen to the 53-year-old patient with multiple myeloma. Clinical results confirmed the treatment planning predictions. After TMI, the patient experienced the expected blood count nadir, followed by successful engraftment. Grade 2 nausea and grade 1 emesis occurred only briefly on day 2 of TMI. Skin erythema, oral mucositis, esophagitis, and enteritis were not observed. This report demonstrates the feasibility and potential dosimetric advantages of selectively delivering myeloablative doses of radiation to bone and marrow using an image-guided tomographic intensity-modulated radiation therapy delivery system. Organ doses are substantially lower than those associated with standard TBI and predict the potential to significantly reduce associated toxicities and allow for dose escalation. The results also suggest that this form of targeted TBI may have potential advantages over other forms of targeted TBI, such as radioimmunotherapy or bone-seeking radionuclide therapy. Ongoing clinical trials will define the maximum TMI and TMLI doses achievable and define the potential advantages and limitations of this new approach for patients undergoing hematopoietic stem cell transplantation.

Adult↗

A phase I trial of (90)Y-DOTA-anti-CEA chimeric T84.66 (cT84.66) radioimmunotherapy in patients with metastatic CEA-producing malignancies.

PURPOSE/OBJECTIVE: Previous radioimmunotherapy (RIT) clinical trials at this institution with (90)Y-labeled cT84.66 anti-CEA (carcinoembryonic antigen) evaluated the antibody conjugated to diethylenetriaminepentaacetic acid (DTPA). The aim of this phase I therapy trial was to evaluate cT84.66 conjugated to the macrocyclic chelate (90)Y-DOTA and labeled with (90)Y in a comparable patient population. EXPERIMENTAL DESIGN: Patients with metastatic CEA-producing cancers were entered in this trial. If antibody targeting to tumor was observed after the administration of (111)In-DTPA cT84.66, the patient then received the therapy infusion of (90)Y-DOTA-cT84.66 1 week later. Serial nuclear scans, blood and urine collections, and computed tomography (CT) scans were performed to assess antibody biodistribution, pharmacokinetics, toxicities, and antitumor effects. RESULTS: Thirteen (13) patients were treated in this study. Dose-limiting hematologic toxicity was experienced at initial starting activity levels of 12 and 8 mCi/m(2). Subsequent patients received systemic Ca-DTPA at 125 mg/m(2) every 12 hours for 3 days post-therapy to allow for a dose escalation to 16 mCi/m(2), where hematologic toxicity was observed with an associated maximum tolerated dose (MTD) of 13.4 mCi/m(2). Tumor doses ranged from 4.4 to 569 cGy/mCi, which translated to 97-12,500 cGy after a single infusion of (90)Y-DOTA-cT84.66. Human anti-chimeric antibody (HACA) response developed in 8 of 13 patients and prevented additional therapy in 4 patients. CONCLUSIONS: This study demonstrates the feasibility of using (90)Y-DOTA-cT84.66 for antibody-guided radiation therapy. Immunogenicity of the DOTA-conjugated cT84.66 antibody was not appreciably greater than that observed with (90)Y-DTPA-cT84.66 in previous trials. Dose-limiting hematopoietic toxicity with (90)Y-DOTA-cT84.66 decreased with Ca-DTPA infusions post-therapy and appears to be comparable to previously published results for (90)Y-DTPA-cT84.66. The highest antibody uptake and tumor doses were to small nodal lesions, which supports the predictions from preclinical and clinical data that RIT may be best applied in the minimal tumor burden setting.

Adult↗

Optimizing reproducibility for clinical studies involving patch testing and application of topical preparations.

BACKGROUND: The reproducibility and consistency of patch-test techniques can be problematic, making controlled clinical trials of patch testing difficult. OBJECTIVE: To measure the accuracy and reproducibility of applying controlled quantities of petrolatum onto Finn Chambers. METHODS: Four dermatology nurses applied a total of 240 samples of white petrolatum, using three syringe sizes and types. Three different amounts of white petrolatum (0.02 mL, 0.05 mL, and the "usual" amount) were expressed onto previously weighed Finn Chambers, using three different syringe sizes (5 mL, 1 mL, and 0.5 mL), five times each on two separate days. RESULTS: The average weights of 0.05 mL of petrolatum expressed with each type of syringe (5 mL: 0.04252 g; 1 mL: 0.04084 g; and 0.5 mL: 0.04139 g) were not significantly different from each other in pairwise comparisons (p > .36) or from the "gold standard" expected value (0.04138 g, p > .72). The average weights of 0.02 mL of petrolatum expressed with two types of syringes (5 mL: 0.02138 g; 0.5 mL: 0.01778 g) were significantly different from each other (p = .0012), but neither differed significantly from the expected value (0.01655 g, p > .08). The variance due to the effect modifications of nurse, day, and interaction of nurse and day was statistically significant for measurements made with the 5 mL syringe but not for measurements made with the 1 mL or 0.5 mL syringe. CONCLUSION: The average amounts of petrolatum extruded from smaller syringes (0.5 mL and 1 mL) were less variable and more reproducible than those extruded from a 5 mL syringe.

Administration, Cutaneous↗

Organ sparing by conformal avoidance intensity-modulated radiation therapy for anal cancer: dosimetric evaluation of coverage of pelvis and inguinal/femoral nodes.

PURPOSE: To describe a novel and straightforward conformal avoidance intensity-modulated radiation therapy (IMRT) technique for coverage of pelvis and inguinal/femoral nodes and to compare the dosimetry of the new method with that of other traditional methods of radiation treatment. METHODS AND MATERIALS: Data of 2 patients with anal cancer were used as example cases to illustrate details and advantages of conformal avoidance IMRT technique. Conventional photons with enface electrons design was created first, thereby providing "outermost boundaries" defined as planning target volume (PTV) for subsequent conformal avoidance IMRT design. Organs at risk (OARs), including femoral head and neck and external genitalia, were contoured as conformal avoidance structures. A step-and-shoot inverse IMRT planning was subsequently generated. For dosimetric comparison, a recently published technique by modified segmental boost was also generated. These treatment techniques were evaluated by dose-volume histogram (DVH) of PTV and OARs. Dose profiles at four different depths from each treatment planning were generated for comparison. RESULTS: The DVH of PTV showed that coverage of the PTV was comparable among three treatment techniques. Percent volume of PTV receiving more than 90% prescription dose was in the range 94-98% for the three treatment techniques, and all had only 0-2% of PTV receiving more than 110% of prescription dose. The DVH of OARs confirmed that both femoral head and neck and external genitalia could be spared well by conformal avoidance IMRT as compared with the other two techniques. Although greater inhomogeneity of dose distribution within the PTV was noted by conformal avoidance IMRT technique, as shown by dose profiles at four different depths, the maximum doses at different depths were less than 115%, which was comparable to those planned by modified segmental boost technique. Planning by photons and enface electrons technique, however, showed a greater dose variation up to 134% of the prescription dose at 1.5 cm depth along photon-electron match-line. CONCLUSIONS: To cover pelvis and inguinal/femoral nodes, conformal avoidance IMRT is technically simple to simulate, plan, and execute. Dosimetric study has demonstrated that it achieves comparable PTV coverage compared with other approaches while at the same time significantly sparing the surrounding OARs.

Aged↗

STS gene in a pedigree with X-linked ichthyosis.

To investigate the gene mutation in a pedigree with X-linked ichthyosis (XLI) and to explore the relationship between the mutation and its clinical manifestations, genomic DNA of affected members, the normal member of the pedigree and 50 unrelated normal members was extracted with a whole blood genomic DNA extraction kit and the DNA was used as a template for the polymerase chain reaction (PCR)-mediated amplification of exon 1 and exon 10 of the STS gene. hHb6 (human hair basic keratin) gene was used as the internal control. Our results showed that the STS gene was deleted in affected members in the pedigree with X-linked ichthyosis. The normal member of the pedigree and 50 unrelated normal members had no such deletion. The proband and his mother had products in the internal control after PCR amplification. The blank control had no product. It is concluded that deletion of the STS gene existed in this pedigree with X-linked ichthyosis, and it is responsible for the unique skin lesions of X-linked ichthyosis.

Adult↗

Improved preservation of human red blood cells by lyophilization.

The lyophilization of human red blood cells has important implications for blood transfusion in clinical medicine. In this study, sugars, human serum albumin, polyvinylpyrrolidone, and dimethyl sulfoxide were used as protective reagents for the lyophilization of red blood cells. Freezing temperature, shelf temperature, and the rehydration conditions were optimized. The results showed that extracellular disaccharides, especially trehalose, did not increase the recovery of hemoglobin. However, when the concentration of human serum albumin was higher than 25%, it had a considerable protective effect on the recovery of lyophilized red blood cells; the cellular hemoglobin recovery was over 70%, which was significantly higher than that in the group without human serum albumin (P<0.01). As the concentration of polyvinylpyrrolidone was increased, the extent of vitrification also increased. But when the concentration of polyvinylpyrrolidone was over 40%, the resulting concentration of free hemoglobin was over 1g/L, which was significantly higher than that with 40% (P<0.01). When lyophilization was carried out after freezing at different temperatures, the recovery of cells and hemoglobin was 70-80% and there were no significant differences among the five groups. When the shelf temperature was higher than -30 degrees C, the samples were partly collapsed, but when the shelf temperature was lower than -30 degrees C, the recovery of cells in the -40 and -45 degrees C groups was significantly higher than in the -30 and -35 degrees C groups (P<0.05). The recovery of cells and hemoglobin after lyophilization and rehydration in solutions containing low concentrations of polymers was over 80%, which is significantly higher than the other groups (P<0.01). In addition, when the temperature was higher than 25 degrees C, the concentration of free hemoglobin was significantly lower than it was at 4 degrees C (P<0.01). In conclusion, our study showed the lyophilization of red blood cells is feasible. Disaccharides have no protective effect on lyophilized cells when they are only extracellular and extensive vitrification may be not beneficial. Although the recovery of cells after lyophilization and rehydration by our method was over 70%, the ultrastructure of the cells may be compromised and some hemolysis does still exist. Further research is required.

Blood Preservation↗

Estimation of cancer drug potencies and relative potencies from in vitro data.

A method is proposed for the estimation of drug or toxicity potencies using in vitro data. A typical experiment in cancer research is presented where cells from a tumor-derived cell line were deposited as fixed volumes in 12-well cell culture plates. After waiting for 72 hours (for further growth), the wells were exposed to different concentrations of a drug and, at the end of the experiment, the numbers of surviving cells were counted. In this article, the "standard model" is extended to take explicit account of the error structure generated by the two experimental stages, namely, the cell deposition stage (and growth, prior to challenging by drug) and the cell counting stage (by hemacytometer) that are fundamental to the design but have usually been ignored in the modeling process. A simulation study illustrates substantial gains in efficiency in the estimation of the median effective dose.

Animals↗

Imaging glioma extent with 131I-TM-601.

UNLABELLED: TM-601, a 36-amino-acid peptide, selectively binds to glioma cells but not normal brain parenchyma. A phase I/II clinical trial of intracavitary 131I-TM-601 in adult patients with recurrent high-grade glioma was performed to determine the biodistribution and toxicity of this potential therapy. We evaluated imaging and biodistribution data from this trial to assess whether 131I-TM-601 might be useful in determining tumor extent. METHODS: Adult patients with recurrent high-grade gliomas underwent tumor resection, implantation of an intracavitary reservoir, and a single-dose injection of 370 MBq (10 mCi) 131I-TM-601 (0.25-1.0 mg of 131I-TM-601) 2-4 wks after surgery. Total-body planar scans and whole-brain SPECT scans were obtained on days 0, 1, 2, 3, and 6-8 after injection. Postresection MR images were coregistered to the SPECT scans using image analysis software. Analysis of the rate of radioactive decay and biologic elimination from the body and at the cavity site was performed. T1-weighted with gadolinium contrast (T1-Wc), T2-weighted (T2), and SPECT volumes were estimated by stereological Cavalieri sections and compared for overlap. RESULTS: Nonbound 131I-TM-601 was eliminated by 48 h after injection with the remaining radiolabeled peptide bound to tumor for at least 6-8 d. Biologic decay rates from 24 to 168 h after injection were only slightly shorter than the physical decay of 131I (6.3 vs. 8.0 d). A comparison of tumor volume estimates using all 3 imaging parameters indicated that 131I-TM-601-determined tumor volumes more closely paralleled T2 volumes than T1-Wc volumes. Overlap between coregistered MRI and SPECT scans corroborated the presence of radiolabeled peptide in the vicinity of infiltrating tumor up to 168 h after injection. CONCLUSION: 131I-TM-601 provides a reliable estimate for primary tumor extent. Further modification of this radiopeptide with other better imaging isotopes may provide an important tool for determining tumor extent and differentiating regions of viable tumor from necrosis.

Adult↗

[Investigation of steroid sulfatase gene in two pedigrees with X-linked ichthyosis].

OBJECTIVE: To investigate the gene mutation in two pedigrees with X-linked ichthyosis (XLI) and explore the relationship between the mutation and clinical manifestations. METHODS: Genomic DNA of the affected and normal members of the pedigrees and 50 unrelated normal subjects from different regions was extracted with a whole blood genomic DNA extraction kit for use of the template for PCR amplification of exon 1, exon 2 and exon 10 of the steroid sulfatase (STS) gene. RESULTS: The STS gene was partially deleted in the affected members in the pedigrees with XLI, leaving only exon 1 but not the other exons. The normal member of the pedigree and 50 unrelated normal subjects had no such deletion. CONCLUSION: Partial deletion of the STS gene exists in the two pedigrees with XLI, which is responsible for pathological skin changes characteristic of XLI.

Adolescent↗

[Lyophilization for platelet preservation].

To explore a new lyophilized preservation methods for human platelets, platelets were pre-treated with aldehyde, human albumin or trehalose was added to the system of condensed cooling as protectant to stabilize the structure of platelets. The optimal resuspending buffer was also selected in the study. The morphological changes of platelets were observed by using electron microscopy after lyophilization, and the expression of membrane proteins on platelets was detected also after lyophilization. The results indicated that the recovery rate of platelets treated with aldehyde was generally more than 60%. Aggregative ability was reduced a little than the platelet untreated. 5% of human albumin had an advantage over 40 mmol/L of trehalose in respect of the preservation effect. In the way of keeping aggregative ability, PPP was obviously better than PBS. The results of electron microscopy displayed that organelles including mitochondria and excreted granules could be observed distinctly. Whereas, expression of membrane proteins of platelet treated with aldehyde was evidently dropped as compared with those of the fresh platelet. In conclusion, aldehyde as a novel protective agent, has excellent effects on lyophilization of platelets and is worthy to be further studied.

Albumins↗

[Tendency and mathematical model of relationship of blood ATP content with temperature and time of preservation].

To investigate the relationship of blood ATP content with temperature and time of preservation and to establish its mathematical model, adenosine triphosphate (ATP) concentration was applied as the index of the quality of erythrocytes; systematical study on variation of blood preserved in a series of different temperatures from 4 degrees C to 32 degrees C was performed, and a series of experimental data were obtained. The results showed that when the ATP concentration y = f (d, t, s) in preserved blood was given as the continuous function of the time (d), the temperature (t) and the initiate ATP concentration (s), the model was fitted with the theory of linearity regression in symbolic statistics, and the general mathematical physical equation of the variation of preserved blood quality was deduced. According to the equation, the whole blood in CPDA-1 solution could be efficiently stored for 35, 35, 29, 22, 18, 18, 13, 8, 7, 6, 6, 5, 4, 4 and 3 days in 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 degrees C, respectively. In conclusion, the general tendency of the variation of preserved blood quality according to the temperature and the time was systematically disclosed for the first time, which would be propitious to estimate the blood quality in various temperatures and to instruct clinical blood transfusion.

Adenosine Triphosphate↗