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Biomedical subjects

C C Hsu

Publications and source records attributed to C C Hsu.

At least 91 records · Page 5Linked to original sources

The expression of soluble intercellular adhesion molecule-1 in endometriosis.

OBJECTIVE: To investigate the association between concentrations of soluble intercellular adhesion molecule-1 (ICAM-1) and interferon-gamma (IFN-gamma) with regard to the severity of endometriosis. DESIGN: Cross-sectional study. SETTING: Infertility unit in a university hospital. PATIENT(S): Seventy-one infertile patients who underwent laparoscopic evaluation were divided into two groups: 36 patients with endometriosis served as cases, and 35 patients without endometriosis served as control subjects. INTERVENTION(S): Peripheral blood and peritoneal fluid (PF) were collected from these patients during laparoscopic examination. MAIN OUTCOME MEASURE(S): Quantitative determination of levels of human ICAM-1 and IFN-gamma was performed with the use of an ELISA. The data were evaluated by Student's t-test, analysis of variance, and regression analysis. RESULT(S): Significantly elevated levels of soluble ICAM-1 were found in the sera of patients with endometriosis, especially those with advanced stages of the disease. Decreased IFN-gamma levels, which were negatively correlated with serum levels of soluble ICAM-1, also were noted in the PF of patients with endometriosis. CONCLUSION(S): The increased serum levels of ICAM-1 found in patients with endometriosis may indicate the presence of an active disease process. Further, the increased levels of soluble ICAM-1 in peripheral blood were inversely correlated with the concentrations of IFN-gamma in PF. The increased levels of soluble ICAM-1 in plasma may be associated with an immunologic feedback response that blocks further infiltration of immune cells. These findings may be of value in the diagnosis and evaluation of endometriosis.

Adult↗

Ultrasound-guided interventional procedures in splenic abscesses.

The results of ultrasound (US)-guided interventional procedures over a period of 12 years in 21 consecutive patients with splenic abscess were reviewed. The interventional procedures were done with 21- or 18-gauge needles for aspiration of relatively small abscesses (< 3.5 cm) in eight patients and with an 8.3-9.0 French pigtail catheter for continuous drainage in 13 patients with larger abscesses (> or = 3.5 cm). In some patients, multiple abscesses were treated separately according to their various sizes. More than one catheterization were done in three patients because of detached catheter or recurrent abscesses. The interventional procedures were followed by at least eight weeks of appropriate antibiotic therapy. Only one patient had the complication of minimal subcapsular hematoma which needed no further treatment. All the patients had uneventful clinical courses. US-guided interventional procedure proved to be a treatment-of-choice for splenic abscess, and may avoid splenectomy by conserving the spleen.

Abscess↗

Effect of mannitol crystallization on the stability and aerosol performance of a spray-dried pharmaceutical protein, recombinant humanized anti-IgE monoclonal antibody.

We have examined the stability and aerosol performance of the pharmaceutical protein recombinant humanized anti-IgE monoclonal antibody (rhuMAbE25) spray dried with mannitol. The aerosol performance was measured by the fine particle fraction (FPF), and stability was assessed by the formation of soluble aggregates. When mannitol was added to the spray-dried rhuMAbE25 formulation, its ability to stabilize the protein leveled off above about 20% (w/w, dry basis). The FPF of the spray-dried formulations was stable during storage for rhuMAbE25 containing 10% and 20% mannitol, but the 30% formulation exhibited a dramatic decrease upon storage at both 5 degreesC and 30 degreesC, due to mannitol crystallization. We tested the addition of sodium phosphate to a 60:40 rhuMAbE25:mannitol (w:w) mixture, which otherwise crystallized upon spray drying and yielded a nonrespirable powder. The presence of sodium phosphate was successful in inhibiting mannitol crystallization upon spray drying and dramatically lowering the rate of solid-state aggregation. However, over long-term storage some crystallization was observed even for the phosphate-containing samples, concomitantly with increased particle size and decreased suitability for aerosol delivery. Therefore, the physical state of mannitol (i.e., amorphous or crystalline) plays a role both in maintaining protein stability and providing suitable aerosol performance when used as an excipient for spray-dried powders. Agents which retard mannitol crystallization, e.g., sodium phosphate, may be useful in extending the utility of mannitol as an excipient in spray-dried protein formulations.

Antibodies, Anti-Idiotypic↗

Effect of excipients on the stability and structure of lyophilized recombinant human growth hormone.

We have investigated the effect of mannitol, sorbitol, methyl alpha-D-mannopyranoside, lactose, trehalose, and cellobiose on the stability and structure of the pharmaceutical protein recombinant human growth hormone (rhGH) in the lyophilized state. All excipients afforded significant protection of the protein against aggregation, particularly at levels to potentially satisfy water-binding sites on the protein in the dried state (i.e., 131:1 excipient-to-protein molar ratio). At higher excipient-to-protein ratios, X-ray diffraction studies showed that mannitol and sorbitol were prone to crystallization and afforded somewhat less stabilization than at lower ratios where the excipient remained in the amorphous, protein-containing phase. The secondary structure of rhGH was determined using Fourier transform infrared (FTIR) spectroscopy. rhGH exhibited a decrease in alpha-helix and increase in beta-sheet structures upon drying. Addition of excipient stabilized the secondary structure upon lyophilization to a varying extent depending on the formulation. Samples with a significant degree of structural conservation, as indicated by the alpha-helix content, generally exhibited reduced aggregation. In addition, prevention of protein-protein interactions (indicated by reduced beta-sheet formation) also tended to result in lower rates of aggregation. Therefore, in addition to preserving the protein structure, bulk additives that do not crystallize easily and remain amorphous in the solid state can be used to increase protein-protein distance and thus prevent aggregation.

Drug Stability↗

Investigation on fouling mechanisms for recombinant human growth hormone sterile filtration.

During sterile filtration of recombinant human growth hormone solutions, severe membrane fouling was experienced compared to other protein preparations of significantly higher molecular weights and concentrations. This phenomenon was attributed to rhGH aggregation/adsorption occurring in the filter pore. To better understand this phenomenon, we examined several possible fouling mechanisms: (1) pore constriction, (2) adsorption due to nonspecific binding between protein and the membrane, (3) shear-induced adsorption, (4) hydrophobic interface-induced aggregation/adsorption. The protein solutions were sterily filtered using 0.22 mm filters, and their filtration fluxes were monitored. Filtration on the capillary and the noncapillary filters suggested that constraints by pore constriction and tortuosity played only a limited role. Filtration using filters with different degrees of protein binding tendency suggested that nonspecific adsorption was insignificant. The shear stress acting on the protein during filtration was small. RhGH which was intentionally sheared in a high-speed concentrically rotating device did not aggravate fouling tendency, suggesting that the shear-induced adsorption might not be the major fouling mechanism. The dynamic light scattering data showed a trace amount of rhGH aggregates always present in equilibrium with the hydrophobic (air-water and membrane-water) interface. These aggregates tended to be adsorbed to the membrane, and more aggregates were generated presumably due to the equilibrium between aggregates and protein monomers. This adsorption/aggregation process eventually fouled the membrane. When the hydrophobic interface was occupied by surfactant molecules, the equilibration kinetics ceased to generate aggregates, thereby minimizing membrane fouling. This study clarified the cause of such an unusual fouling phenomenon upon microfiltration.

Adsorption↗

Effect of spray drying and subsequent processing conditions on residual moisture content and physical/biochemical stability of protein inhalation powders.

PURPOSE: To understand the effect of spray drying and powder processing environments on the residual moisture content and aerosol performance of inhalation protein powders. Also, the long-term effect of storage conditions on the powder's physical and biochemical stability was presented. METHODS: Excipient-free as well as mannitol-formulated powders of a humanized monoclonal antibody (anti-IgE) and recombinant human deoxyribonuclease (rhDNase) were prepared using a Buchi 190 model spray dryer. Residual moisture content and moisture uptake behavior of the powder were measured using thermal gravimetric analysis and gravimetric moisture sorption isotherm, respectively. Protein aggregation, the primary degradation product observed upon storage, was determined by size-exclusion HPLC. Aerosol performance of the dry powders was evaluated after blending with lactose carriers using a multi-stage liquid impinger (MSLI). RESULTS: Spray-dried powders with a moisture level (approximately 3%) equivalent to the freeze-dried materials could only be achieved using high-temperature spray-drying conditions, which were not favorable to large-male manufacturing, or subsequent vacuum drying. These dry powders would equilibrate with the subsequent processing and storage environments regardless of the manufacturing condition. As long as the relative humidity of air during processing and storage was lower than 50%, powders maintained their aerosol performance (fine particle fraction). However, powders stored under drier conditions exhibited better long-term protein biochemical stability. CONCLUSIONS: Manufacturing, powder processing, and storage environments affected powder's residual moisture level in a reversible fashion. Therefore, the storage condition determined powder's overall stability, but residual moisture had a greater impact on protein chemical stability than on powder physical stability.

Administration, Inhalation↗

Effect of dexamethasone on postoperative emesis and pain.

In this double-blind, randomized, placebo-controlled study, we have evaluated the effect of preoperative administration of dexamethasone on postoperative vomiting and pain in 60 women undergoing general anaesthesia for major gynaecological surgery. Dexamethasone 10 mg (group D) or saline (group S) was administered i.v. in a double-blind manner during induction of anaesthesia. Postoperative pain relief was controlled with bolus doses of morphine using an i.v. patient-controlled analgesia device, and patients were assessed for incidence of vomiting, sedation score, verbal pain rating score, time to first morphine demand and morphine consumption at 4, 8, 12 and 24 h after surgery. Six patients in group D and 19 in group S experienced vomiting at least once within the 24-h postoperative period; dexamethasone was effective in reducing the overall incidence of vomiting from 63.3% to 20.0% (P < 0.01). Other variables were similar between the groups, and the influence of dexamethasone on postoperative pain was minimal.

Analgesics, Opioid↗

Bilirubin binding activity of cytokeratin 18 isolated from the porcine liver.

A porcine liver 40 kDa protein designated SBP40 isolated by affinity chromatography with agarose-linked spermine was identified as a porcine cytokeratin 18 on the basis of partial amino acid sequences of peptides derived by lysylendopeptidase digestion and by its reactivity with two commercially available preparations of monoclonal antibody. Immunohistochemistry revealed that SBP40 is localized at the hepatocyte membranes, preferentially in the bile canalicular area in accordance with the previously reported localization of cytokertain 18 in the murine liver. Affinity chromatography with agarose-linked bilirubin, a solubilization experiment of bilirubin from bilirubin-Sephadex G-10 complex, and gel-filtration of a mixture with bilirubin demonstrated that SBP40 or porcine cytokeratin 18 has binding affinity for bilirubin. These results suggest that cytokeratin 18 may play a role as a membrane reservoir in the event of transport and secretion of bile pigments in the liver.

Amino Acids↗

Triangular fibrocartilage of wrist: presentation on high resolution ultrasonography.

This study consisted of two parts. Part I is for detection of the normal triangular fibrocartilage by high resolution ultrasonography and Part II is a preliminary study to evaluate high resolution ultrasonography in the diagnosis of tears of the triangular fibrocartilage. Normally, the triangular fibrocartilage was seen in all cases in Part I as an inverse triangular structure of homogeneous hyperechogenicity on transverse and oblique sagittal scans at the level of the distal radioulnar joint. At its waist it measured from 2.3 to 4.2 mm (mean, 3.0 +/- 0.5 mm) on oblique sagittal scan and from 2.5 to 3.7 mm (mean, 3.2 +/- 0.4 mm) on transverse scan. Under normal conditions, the triangular fibrocartilage is thicker than 2.5 mm on both transverse and oblique sagittal sections with a confidence level of 95%. In Part II, eight of the 47 wrists were found to be hypoechoic in the triangular fibrocartilage region, which proved to be tears by arthrography. Six cases showed a homogeneous hyperchoic triangular fibrocartilage measuring from 1.8 to 2.8 mm (mean, 2.3 +/- 0.5 mm) in transverse section and from 0 to 2.2 mm (mean 1.2 +/- 1.1 mm) in oblique sagittal section; five of these proved to be tears by arthrography. In contrast, 33 wrists had a homogeneous hyperechoic triangular fibrocartilage measuring from 2.5 to 4 mm (mean, 3.1 +/- 0.4 mm) and 2.5 to 4.2 mm (mean, 3.1 +/- 0.6 mm) on transverse and oblique sagittal sections, respectively; 27 proved to be normal triangular fibrocartilage by arthrography. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 68.4%, 96.4%, 92.9%, 81.8%, and 85.1%, respectively. HRUS can display the normal triangular fibrocartilage as a homogeneous hyperechoic and inverted triangular structure. The torn triangular fibrocartilage appears as a hypoechoic region or as thinning (< 2.5 mm) of the hyperechoic structure on either transverse or oblique sagittal section. HRUS has an acceptable accuracy in the diagnosis of triangular fibrocartilage tear.

Adolescent↗

Cubital tunnel syndrome: diagnosis by high-resolution ultrasonography.

The purpose of this study was to evaluate the morphologic changes in the ulnar nerve in cubital tunnel syndrome with high-resolution ultrasonography. The mean values of the short axis (cm) x long axis (cm) at the arm, epicondyle, and forearm levels were 0.057 +/- 0.01, 0.068 +/- 0.019, and 0.062 +/- 0.01 in control group; 0.069 +/- 0.04, 0.139 +/- 0.06, and 0.066 +/- 0.023 in the symptomatic side in patients with cubital tunnel syndrome; and 0.063 +/- 0.029, 0.068 +/- 0.029, and 0.057 +/- 0.012 in the normal side in patients with cubital tunnel syndrome. No significant difference was found in the area (short axis x long axis) of the ulnar nerve at the arm, epicondyle and forearm levels between the left and right ulnar nerve in the control group and between the control group and the normal side in symptomatic patients. However, the mean value of the area of the ulnar nerve at the epicondyle level in symptomatic patients was significantly larger than that of the control group and that of the contralateral side in patients, and the P value was less than 0.001. High resolution ultrasonography can detect morphologic changes in the ulnar nerve accurately, and it could therefore be useful as a screening and even follow-up modality in patients with cubital tunnel syndrome.

Adult↗

Verifying complete obliteration of carotid artery-cavernous sinus fistula: role of color Doppler ultrasonography.

The purpose of this study was to evaluate the role of color Doppler ultrasonography in verifying obliteration of carotid artery-cavernous sinus fistula before and after therapeutic embolization or gamma knife radiosurgery. Before treatment, carotid artery-cavernous sinus fistula showed the following data on color Doppler ultrasonography: (1) increased blood flow in the common carotid artery (220 to 1264 ml/min with mean+/-SD of 728+/-378 ml/min); internal carotid artery (435 to 1097 ml/min with mean+/-SD of 834+/-216 ml/min) in fistulas of the direct type; and external carotid artery (85 to 257 ml/min with mean+/-SD of 170+/-75 ml/min) in fistulas of the indirect type in comparison to the contralateral side; (2) reverse pulsatile flow or spiculated wave form with turbulent flow in the engorged superior ophthalmic vein on the lesion side in all patients. All of the above abnormal hemodynamic changes became normal in six patients immediately after first embolization, in two patients with balloon embolization combined with subsequent direct embolization by direct puncture through the superior orbital fissure or internal carotid artery embolization, and in five patients after gamma knife radiosurgery at 4, 4, 8, 9, and 9 months, respectively. Color Doppler ultrasonography might be a good modality in long-term follow-up of carotid artery-cavernous sinus fistula after gamma knife radiosurgery and embolization.

Adolescent↗

Ischemic stroke in a young woman with ovarian hyperstimulation syndrome.

We present a case of right middle cerebral artery occlusion after a controlled ovarian hyperstimulation regimen and cryopreserved embryo transfer (ET) in a previously healthy 22-year-old woman. The patient suffered from nausea and progressive abdominal distension 8 days after ET. Under the diagnosis of ovarian hyperstimulation syndrome, she was treated with hypertonic solution, albumin infusion, and paracentesis, with some improvement. Left hemiparesis and dysarthria occurred suddenly on the fourth day of hospitalization, 11 days after ET. The neurologic deficits progressed to complete hemiplegia within a few hours. Computed tomography of the head showed infarction in the territory of the right middle cerebral artery. Magnetic resonance angiography revealed occlusion of the main trunk of the right middle cerebral artery. Laboratory studies showed leukocytosis with neutrophil predominance and a hypercoagulable state. The pregnancy was terminated because of progressive tachycardia, dyspnea, and increased abdominal girth despite supportive treatment. The neurologic deficits remained stationary at the time of discharge. This case emphasizes that the recent advent of ovulation induction and assisted reproductive techniques is a newly recognized cause of devastating cerebral infarction in otherwise healthy women.

Adult↗

Detection of endogenous digitalis-like immunoreactive factors in human blood.

Digitalis-like immunoreactive factors (DLIF) are special types of steroids with lactone rings in their structures. Clinically, this type of compound can be used as medicine for heart failure; thus, the elevated endogenous DLIF found under certain pathological conditions are interferent substances in digoxin immunoassay. Endogenous DLIF with biological and immunological properties similar to cardiotonic drugs, such as digoxin, have been found in several tissues and body fluids of animals and humans. Since these endogenous Na+, K(+)-ATPase inhibitors can be considered hormones in nature, immunoassays must be selected detection of them to achieve the required sensitivity and specificity. In this study, we used three sets of in-house formulated immunoassays for DLIF and ouabain-like factors (OLF) detection. Using a polyclonal antibody-based ouabain enzyme immunoassay, the mean +/- S.E.M. of OLF in the sera of 10 healthy individuals were determined to be (9.1 +/- 0.9) x 10(-11) M. Using a monoclonal antibody-based ouabain enzyme immunoassay, the mean +/- S.E.M of OLF in the sera of 10 healthy individuals was (8.2 +/- 1.2) x 10(-11) M while using a antibody fragment Fab-based enzyme immunoassay for digoxin, the mean +/- S.E.M of DLIF in 11 healthy individuals was (4.0 +/- 1.2) x 10(-10) M. In conclusion, our immunological data indicate that DLIFs are normal constituents of human blood. Although DLIF is the major component, coexistence of OLF with DLIF in healthy individuals can not be excluded.

Animals↗

Effects of thrombin on the growth, protein synthesis, attachment, clustering and alkaline phosphatase activity of cultured human periodontal ligament fibroblasts.

Previous studies have indicated that thrombin can activate pulp cells, including fibroblasts. Because pulp cells and periodontal ligament (PDL) fibroblasts can express thrombin receptor mRNA, the specific aim of this study was to determine whether thrombin can activate the growth, attachment, protein synthesis, alkaline phosphatase activities and cellular clustering of cultured human PDL fibroblasts. Thrombin can stimulate the growth of PDL fibroblasts in a dose dependent manner (as analyzed by MTT assay). At concentrations of 5 and 10 U/ml, thrombin increased the cell numbers to 141% and 153% greater than that of the control after 5 days of incubation, respectively. Thrombin (5-20 U/ml) also stimulated the protein synthesis rate (assayed by [3H]proline incorporation) to 1.88-2.13 fold that of the control. However, pretreatment of PDL fibroblasts with thrombin (1-20 U/ml) could not promote the attachment of PDL fibroblasts to type I collagen and fibronectin. Moreover, thrombin could induce clustering of PDL fibroblasts within a concentration range of 5-20 U/ml. However, thrombin (1-20 U/ml) exerted neither stimulatory nor inhibitory effect on cellular alkaline phosphatase activities. In conclusion, it appears that the presence of thrombin seems to have effects on PDL fibroblasts in terms of cell growth, protein synthesis and cell clustering. This suggests that thrombin might be important in the early healing process of periodontium following periodontal surgery.

Alkaline Phosphatase↗

Lead exposure causes generation of reactive oxygen species and functional impairment in rat sperm.

The relationships between blood lead, sperm lead, sperm reactive oxygen species (ROS) level, and sperm fertile capability were investigated to understand the effects of lead exposure on sperm function and the mechanism of these effects. Male Sprague-Dawley rats, 7 weeks old, were randomly divided into control group and lead-treated group. The controls and lead-treated animals received intraperitoneal injection of 10 mg sodium acetate and 10 mg lead acetate/kg body weight, respectively, weekly for 6 or 9 weeks. The blood lead and epididymal sperm lead were analyzed by graphite furnace atomic absorption spectrophotometer. Chemiluminescence was measured to evaluate the generation of sperm ROS. Sperm-oocyte penetration rate (SOPR) was measured to evaluate sperm function. After 6 weeks of lead exposure, the rats had average blood lead levels of 32 microg/dl, sperm lead levels of 0.67 +/- 0.11 microg/10(9) sperm, unchanged epididymal sperm counts, percent of motile sperms, and motile epididymal sperm counts compared with control animals. However, after 9 weeks of lead exposure, the rats had average blood lead levels of 48.0 +/- 4.3 microg/dl, sperm lead levels of 0.88 +/- 0.16 microg/10(9) sperm, statistically lower epididymal sperm counts, and lower motile epididymal sperm counts. There was a good correlation between the blood lead and sperm lead(r2 = 0.946, P < 0.001). The sperms of lead-exposed rats produced significantly higher counts ofchemiluminescence than did those from the control rats (P < 0.001). The chemiluminescence counts were positively associated with sperm lead level (r2 = 0.613, P < 0.001). Epididymal sperm counts, motility and motile epididymal sperm counts were negatively associated with sperm chemiluminescence (r2 = 0.255, 0.152, and 0.299; P < 0.01, 0.05, and 0.01, respectively). The SOPR were positively associated with epididymal sperm counts, motility and motile epididymal sperm counts (r2 = 0.136, 0.285, and 0.264; P < 0.05, 0.01, and 0.001, respectively). The sperm chemiluminescence was negatively associated with SOPR (r2 = 0.519, P < 0.001). It is concluded that lead exposure probably affected the sperm function by activating one of the pathways of ROS generation.

Animals↗

Protein phosphorylation and taurine biosynthesis in vivo and in vitro.

Taurine is known to be involved in many important physiological functions. Here we report that both in vivo and in vitro the taurine-synthesizing enzyme in the brain, namely cysteine sulfinic acid decarboxylase (CSAD), is activated when phosphorylated and inhibited when dephosphorylated. Furthermore, protein kinase C and protein phosphatase 2C have been identified as the enzymes responsible for phosphorylation and dephosphorylation of CSAD, respectively. In addition, the effect of neuronal depolarization on CSAD activity and 32P incorporation into CSAD in neuronal cultures is also included. A model to link neuronal excitation and CSAD activation by a Ca2+-dependent protein kinase is proposed.

Animals↗

Prenatal sonographic diagnosis of single umbilical artery.

PURPOSE: We evaluated the reliability of prenatal sonography and the usefulness of the umbilical vein and artery diameter ratio, transverse umbilical artery diameter, and systolic-diastolic ratio in detecting single umbilical artery (SUA). METHODS: In 24 of 6,970 fetuses, SUA was detected using prenatal sonography and confirmed at birth. These cases were retrospectively reviewed. RESULTS: Four fetuses had major malformations, and 1 had a minor anomaly. Thirteen fetuses with SUA underwent chromosomal analysis, and only 2 had abnormal karyotypes. Most of the SUA fetuses had a normal systolic-diastolic ratio. CONCLUSIONS: Our retrospective study determined that the prognosis of SUA fetuses is good when there is no concurrent anatomic or chromosomal abnormality. Although some reports claim that the transverse umbilical artery diameter or the ratio between umbilical vein and artery diameters can predict SUA, we found no significant improvement in the recognition of SUA using these parameters.

Adult↗