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Biomedical subjects

S M Kuo

Publications and source records attributed to S M Kuo.

At least 37 records · Page 2Linked to original sources

Animal study of phoenix total artificial heart implantation.

BACKGROUND: It is well accepted that a total artificial heart (TAH) can be used as a bridge to heart transplantation during the waiting period for organ donation. A series of combined studies, conducted by the Kaohsiung Veterans General Hospital, National Yang-Ming Medical College and Municipal Tainan Hospital, has been performed to improve the Phoenix artificial heart developed by Dr. Kevin Kuo-Tsai Cheng. METHODS: In growing calves (weighed about 80 kg), standard procedures were used to remove the hearts and replace them with the TAHs. Records were made of hemodynamic data, physiological responses, blood biochemistry data and physical activities after operation and until the death of the calves. Finally, autopsies were used to determine the causes of death. RESULTS: A total of 23 calves were studied. Twenty-two of them survived 1 to 12 days, or an average 4.95 days. One survived more than 30 days. All the calves could breathe, stand, eat and void by themselves two hours after operation. Respiratory failure was the major cause of death. CONCLUSIONS: No thrombus within the TAH was noted in the last five cases, meaning that turbulent flow or dead space of the TAH was improved. Better intensive care and prevention of infection will be the next challenge for long-term use of TAH.

Animals↗

Subcellular localization of metallothionein IIA in human bladder tumor cells using a novel epitope-specific antiserum.

Human metallothioneins (hMTs) are a family of highly homologous proteins thought to be critical in cellular protection against toxins. The comparative function of individual isoforms is, however, obscure. Antibodies to individual MT isoforms might help clarify this issue but their generation has been challenging. We now describe a strategy that has successfully produced an epitope-specific antiserum to a major human isoform, hMT IIA. The immunogen, a conjugated tridecyl amino acid synthetic peptide unique to residues 8-20 in hMT IIA (AAGDSCTCAGSCK), yielded an antiserum (B2) that reacted specifically with hMT IIA in a concentration- and titer-dependent manner and showed no reactivity with human or rabbit liver MT I or horse MTs. This antiserum recognized rabbit liver MT II and, surprisingly, also reacted weakly with chicken MT. MT amino acid sequence comparisons and peptide blocking studies suggested aspartate-11 and threonine-14 are important antigenic determinants for B2. Using confocal immunofluorescence microscopy and B2 antiserum, we observed nuclear localization of hMT IIA with human bladder T24 tumor cells in exponential growth but more cytoplasmic localization at confluence. These results suggest the subcellular location of hMT IIA is a function of cell density in T24 bladder carcinoma cells. The general approach of epitope-specific antibodies may be useful for the generation of antibodies to other MT isoforms and for studying the role of individual MT isoforms in biology and toxicology.

Amino Acid Sequence↗

The contribution of intestinal secretion to the dose-dependent absorption of celiprolol.

The contribution of the intestine to the nonlinear absorption of celiprolol in the rat was studied. After intravenous administration of 14C-celiprolol to bile duct-cannulated rats, approximately 9% of the dose was found to be associated with intestinal tissue and its contents. Microhistoautoradiography of frozen intestinal sections showed a time-dependent secretion of celiprolol from the blood into the lumen of the rat intestine. Propranolol, a lipophilic beta-blocker, was also found to be secreted into the intestine in vivo and transported in epithelial cells in both a temperature- and a pH-dependent manner, although to a lesser extent than celiprolol. Consistent with the observations in rats, transport of celiprolol from the basal-lateral to the apical side was found to dominate apical-to-basal transport using human Caco-2 cell monolayers. Additionally, using isolated rat small intestinal epithelial cells, celiprolol was found also to have a time- and temperature-dependent uptake, suggesting the involvement of a carrier-mediated system in its uptake. The uptake was inhibited by 2 mM celiprolol and propranolol and was also found to be pH dependent. Saturation of the carrier-mediated secretion of celiprolol in the intestine may result in enhanced absorption of celiprolol at high doses and account for its observed nonlinear absorption.

Animals↗

Interleukin-1 beta-mediated metallothionein induction and cytoprotection against cadmium and cis-diamminedichloroplatinum.

Metallothioneins (MTs) are major intracellular protein thiols that have been associated with resistance to the cytotoxicity of heavy metals and some cytotoxic anticancer drugs. The accumulation and subcellular location of MT and its functionality were examined in a human hormone-independent prostatic tumor cell line (DU-145) exposed to cytokines that participate in autocrine growth and the acute phase response. Incubation of DU-145 cells with interleukin-1 beta (IL-1 beta) caused a concentration-dependent increase in MT protein reaching a 2- to 3-fold maximum increase 24 to 48 hr after treatment with 10 U of IL-1 beta/ml; smaller increases were seen with human recombinant IL-1 alpha and tumor necrosis factor alpha. DU-145 cells constitutively expressed only MT-IIa and MT-Ie mRNA and the IL-1 beta-mediated increase in MT protein was preceded by a marked elevation solely in MT-IIa mRNA. Basal MT was immunolocalized by confocal microscopy primarily to the nucleus of DU-145 cells with some granular deposits near the cell surface. IL-1 beta treatment increased nuclear MT. DU-145 cells pretreated with IL-1 beta were 2- to 3-fold resistant to the toxicity of CdCl2 and cis-diamminedichloroplatinum(II) (cisplatin). Both MT induction and cytoprotection against CdCl2 and cisplatin were blocked by concomitant incubation with a recombinant human IL-1 receptor antagonist protein. These results suggest the responsiveness of human prostatic tumor cells to cytotoxic electrophilic anticancer drugs can be diminished by direct exposure to the cytokine IL-1 beta, possibly by a mechanism involving MT.

Cadmium↗

Transport of celiprolol across human intestinal epithelial (Caco-2) cells: mediation of secretion by multiple transporters including P-glycoprotein.

1. The transepithelial transport of the beta-adrenoceptor blocking drug, celiprolol, was investigated in monolayers of the well differentiated human intestinal epithelial cell line, Caco-2. 2. The basal-to-apical transport (secretion) of [14C]-celiprolol (50 microM) was 5 times higher than apical-to-basal transport (absorption). In the presence of an excess (5 mM) of unlabelled celiprolol the basal-to-apical transport was reduced by more than 80%, whereas the apical-to-basal transport remained unchanged. 3. Net celiprolol secretion obtained in the concentration range 0.01 to 5 mM displayed saturable kinetics with an apparent Km of 1.00 +/- 0.23 mM and Vmax of 113 +/- 11 pmol/10(6) cells min-1. These results are consistent with saturable active secretion and provide an explanation for the dose-dependent bioavailability of celiprolol. 4. The secretion of celiprolol was sensitive to pH, and decreased in the absence of sodium and in the presence of ouabain, suggesting that transport was coupled to proton and sodium gradients. 5. The secretion of celiprolol was inhibited by substrates for P-glycoprotein (vinblastine, verapamil and nifedipine) and either inhibited or stimulated by typical substrates for the renal organic cation-H+ exchanger (cimetidine, N1-methylnicotinamide, tetraethylammonium and choline), suggesting that there are at least two distinct transport systems. 6. The secretion of celiprolol was also inhibited by other beta-adrenoceptor blocking drugs (acebutolol, atenolol, metoprolol, pafenolol and propranolol) and by the diuretics, acetazolamide, chlorthalidone and hydrochlorothiazide, suggesting that the clinically observed effect of chlorthalidone on the bioavailability of celiprolol occurs at the level of the intestinal epithelium.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The use of transesophageal echocardiography to evaluate the effectiveness of patent ductus arteriosus ligation.

The ligation of patent ductus arteriosus (PDA) is a comparatively easy operation, but some complications are possible. The most common complication is incomplete ligation of the PDA; others include inadvertent ligation of the descending aorta or left pulmonary artery, transient rise in systemic blood pressure and increased left ventricular afterload, and acute right heart failure due to pulmonary hypertension. The completeness of the PDA ligation is usually determined only by the operating physician's experience, including the use of an esophageal stethoscope or a finger on the lesion to feel for vibration. These methods sometimes fail to detect an incomplete ligation. With transesophageal echocardiography (TEE), we have monitored the entire course of the PDA ligation directly without interrupting the surgical procedure, and precisely determined the completeness of the ligation. We also expect that TEE will enable us to avoid other complications as well.

Adolescent↗

Expression of pulmonary metallothionein genes in late gestational lambs.

Metallothioneins (MT) are low molecular weight proteins that are important in providing protection against heavy metals such as cadmium. Other precise physiologic roles for this family of proteins are less clear, but fetal hepatic cell proliferation and differentiation may be regulated through changes in MT levels and attendant MT-mediated regulation of zinc levels. The role of MT in other developing tissue, most notably lung, is far less clear. Although expression of MT has been reported to be extremely low in early postnatal and mature lung, we hypothesized that MT has a more ubiquitous role in organ development and that pulmonary MT levels may be elevated during periods of rapid lung growth. Thus, we studied expression of MT in late-gestation fetal lambs. Sheep are particularly useful because alveolarization of lung parenchyma occurs before birth (by d 120 of a normal 147-d gestation). Immunoreactive MT was localized to bronchial epithelium of fetal, newborn, and mature sheep. The intensity of staining was greatest in the 130-d gestational age (saccular) lung, where positive reaction product was noted in the cytoplasm and nucleus of alveolar epithelial and interstitial cells. We next evaluated MT expression in developing lung tissue using Northern blot analysis and 32P-cDNA probes against the 3'-untranslated regions of mRNA encoding each of four known functional sheep MT (sMT) isoforms. Expression of sMT-II, sMT-Ia, and sMT-Ib was restricted to the saccular stage (120-132 d gestational age), and sMT-Ic mRNA was not detected in pulmonary samples from any stage of development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Surgical repair of ventricular septal defect without ventriculotomy in the first 12 months of life.

Sixty-eight infants with clinical evidence of a large ventricular septal defect (VSD), refractory to conventional medical treatment, underwent surgical closure within the first 12 months of life from August 1987 to June 1991. There were 43 males and 25 females. The ages of the patients ranged from two to 12 months, with a mean age of 6.6 months. The mean body weight of the patients was 5.4 kg (range, 2.3-10 kg). Surgery was performed because of intractable heart failure in 27 infants (39.7%), failure to thrive in 40 (58.8%), repeated pneumonia in 43 (63.2%) and prolonged endotracheal intubation in nine (13.2%). There were 21 patients with a supracristal VSD (30.9%) and 47 patients with perimembranous VSD (69.1%). Nine patients (13.2%) had preoperative cardiac catheterization. Transatrial repair of perimembranous VSDs and transpulmonary repair of supracristal VSDs was used exclusively without ventriculotomy. Surgically induced heart blocks did not occur in any of the patients. Only two patients (2.9%) died during the early postoperative period. Diagnosis in most cases was confirmed by the present advanced integrated color Doppler echocardiographic technology which is widely used by pediatric cardiologists. There was no need to perform cardiac catheterization in most patients with VSDs. The morbidity and mortality were very low. We strongly suggest that for infants with a large VSD, primary repair should be the procedure of choice.

Female↗

Initial results of laser angioplasty under angioscopic guidance for salvage of an ischemic lower limb: preliminary report.

From March to July 1989, nine patients at risk for peripheral artery disease underwent intraoperative Nd:YAG laser angioplasty using angioscopy at the Veterans General Hospital (Taipei, Taiwan, Republic of China). Following the laser angioplasty, balloon dilatation was performed in all cases. Eight men and one woman at an average age of 68 were included in the study (range: 58 to 78 years old). Ischemic symptoms included five patients with disabling claudication, four with pain at rest and one with gangrene on the toes. Eight of the nine patients had complete occlusions ranging from 2 to 19 cm in length. Two patients had high degree multiple segmental stenosis of the superficial femoral artery from 1 to 2 cm in length. Initial clinical success (indicated by relief of symptoms and increase in Doppler ankle pressure and index) and improvement in the angiographic luminal diameter was noted in 9 of 10 occluded vessels (90%) that underwent Nd:YAG laser treatment which was delivered at 10 to 12 watts through laser probes. Prelaser intraluminal diameter increased from 0.05 +/- 0.07 to 0.53 +/- 0.07 mm, Doppler ankle pressure index rose from 0.51 +/- 0.12 to 0.81 +/- 0.12, Doppler ankle pressure increased from 62.44 +/- 16.10 to 104 +/- 21.21 mmHg and the amplitude of pulse volume recorder at ankle level rose from 5.77 +/- 2.80 to 12.11 +/- 2.77 mm as compared with prelaser therapy (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Transatrial-transpulmonary repair of tetralogy of Fallot: extensive infundibular septum resection.

Twenty-seven patients with tetralogy of Fallot underwent total correction during the period from February 1988 through October 1989. Their ages ranged from 11 months to 12 years (mean 3.3 +/- 4.9 years). For 11 patients, the repair was made via the conventional transventricular approach and a partial resection of the infundibular septum. On the other 16 patients, a transatrial-transpulmonary approach was used with total resection of the anterior deviated infundibular septum, with or without a miniventriculotomy incision (1-10 mm). The exposure of the ventricular septal defect (VSD) through the right atrium, and the right ventricular outflow tract (RVOT) through the pulmonary artery in patients with tetralogy of Fallot was excellent. There were no significant differences between transatrial-transpulmonary repair and transventricular repair of the tetralogy of Fallot with respect to pulmonary artery (PA) index (273.2 +/- 36.6 versus 249.9 +/- 63.2 mm2/BSA) or the postoperative ratio of right ventricle/left ventricle (RV/LV) systolic pressure (0.55 +/- 0.16 versus 0.61 +/- 0.17). Postoperative intensive care was simple and uncomplicated, with a significantly lower catecholamine demand, less bleeding, fewer blood transfusions, and shorter stays in the cardiac Intensive Care Unit (ICU). There was no mortality in this series. This method of repair can be successfully accomplished in most patients with tetralogy of Fallot, with resultant preservation of right ventricular function (intact right ventricle).

Child↗

Experimental implantation of human umbilical vein grafts in dogs.

Locally produced human umbilical vein grafts (HUVG), using glutaraldehyde as a stabilizing agent, were implanted into 24 mongrel dogs. Different arterial bypass procedures, using HUVG, were carried out in three experimental groups. In Group I, 2 dogs underwent femorofemoral crossover bypass procedures and 6 dogs received aortoiliac bypass procedures. Thrombus formation was found in all HUVG implants of Group I. In Group II, 8 dogs received abdominal aorta HUVG interposition. In Group III, 8 dogs received abdominal aorta HUVG bypass procedures. Patent HUVG implants without thrombus formation, demonstrated by postoperative angiogram, were found in 6 dogs of Group II and 5 dogs of Group III. Morphological and histological studies of the patent HUVG implants retrieved after sacrifice showed on sign of rejection, biodegeneration, or aneurysmal formation. Our preliminary experience with this cost-effective locally produced human umbilical vein graft material was promising and may pave the way to further clinical applications.

Animals↗

[Results of vascular reconstruction in lower limbs ischemia: a six-year clinical experience].

During the period between Dec. 1982 to Nov. 1988, a total of 412 patients with 471 limbs at risk of peripheral arterial occlusive disease underwent vascular surgical treatment at the Veterans General Hospital. There were 382 men and 30 women, who ranged in age from 20 to 84 years (mean 63.17 +/- 11.85 years). 95 cases were isolated aortoiliac occlusive disease, 94 cases were combined aortoiliac and femoropopliteal disease, 169 cases were femoropopliteal occlusive disease and 54 cases were femorotibialperoneal occlusive disease. Various reconstructive procedures were performed in the these patients. The cumulative limb salvage rate (LSR) exceeded cumulative patency rate (CPR) in all categories and the result of LSR and CPR were 97.6% and 91% for aortoiliac reconstructive surgery in six years, 96% and 77% for above-knee femoropopliteal saphenous vein bypass (SVB) in six years, 79% and 74% for below-knee femoropopliteal SBV and 63% and 34% for femoro-distal SVB in five years. 88% and 76% for above-knee femoropopliteal human umbilical vein (HUV) bypass in four years. 67% and 45% for femoro-distal HUV bypass in three years follow-up period individually. The immediate good symptomatic results of the vascular reconstruction was 88% encountered in isolated aortoiliac disease, 63% in combined aortoiliac and femoropopliteal disease, 70.4% in isolated femoropopliteal disease and only 26% in femorotibial-peroneal disease (FTP). No change symptoms was still higher (33%) in FTP than the other vascular reconstruction due to poor distal runoff in this series. The early postoperative mortality rate was 1.6%, the late mortality rate was 2.7%, the incidence of postoperative complication rate was 13.6%. The major lower limb amputation rate was low as 7% in our series.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Heterogeneity of anion exchangers mediating chloride transport in the proximal tubule.

Three distinct anion exchangers are described that directly or indirectly mediate Cl- transport across the luminal membrane of the proximal tubule cell. Studies on the intact proximal tubule indicate that the Cl(-)-formate exchanger is a major mechanism for Cl- transport under physiologic conditions. As just discussed, the physiologic importance of the Cl(-)-oxalate and SO4 = (oxalate)-CO3 = exchangers mediating Cl- transport across the luminal membrane of the proximal tubule cell is currently unknown. These three anion exchangers are part of a larger group of at least eight distinct anion transporters in the proximal tubule that share with erythrocyte Band 3 the properties of stilbene sensitivity and/or the ability to mediate anion exchange. It is tempting to speculate that these proximal tubule anion transporters are members of a family of proteins structurally related to the prototypic anion exchanger, erythrocyte Band 3. If this is true, comparing the structures of these anion transporters with each other and with Band 3 should provide important insight into the molecular basis for differences in substrate and inhibitor specificity within this family of transport proteins.

Animals↗

Superior mesenteric vein severance from blunt abdominal trauma: report of a case.

Injury of the superior mesenteric vein from blunt abdominal trauma is an uncommon but frequently fatal injury. A 63-year-old man was injured in a motorcycle accident. He was admitted to our hospital in profound shock. Immediate celiotomy revealed superior mesenteric vein injury which was repaired by end-to-end anastomosis. Rapid fluid resuscitation and expeditious exploration are the key in saving patients with this condition. Indications for exploration of retroperitoneal hematomas, techniques of exposure, modes of reconstruction of the injured vein and the importance of a second-look operation are discussed.

Abdominal Injuries↗

[A new operation for the management of gastric varix bleeding].

Gastric varices is a special oriental type manifestation of gastroesophageal collaterals in portal hypertension patients. It has gained more attention in recent years following the popularity of endoscopy and sclerotherapy. Catastrophic bleeding from ruptures of gastric varices is a life threatening emergency. Gastric varices are generally located at the greater curvature side of the cardiofundic region. Neither a Sengstaken-Blakemore balloon tube nor a Linton balloon tube can stop the bleeding. This area is also beyond the field of sclerotherapy. Surgery is the only definite therapy. Devascularization procedures as described by Dr. Hassab sometimes fail to control active bleeding and also fail to adequately decongest the whole varices area. The radical resection procedures such as terminal esophagectomy, proximal gastrectomy or cardiectomy as proposed by Japanese groups interrupts the normal esophgo-gastric continuity and is also too invasive for a cirrhotic patient. In between, besides terminal esophago-proximal gastric devascularization and splenectomy, we use a TA-90 stapler to perform an oblique cardiofundectomy to resect en bloc the tortuous gastric varices area. From Nov. 1983 to May 1988, at the Veterans General Hospital-Taipei, 16 patients received this new operation to manage gastric varices bleeding. Ten of them were on an emergency basis and 6 were elective surgery. Only one patient in the emergency group died. All catastrophic bleeding in the emergency group was dramatically controlled and all other patients recovered rapidly. With a follow-up range from 6 months to 4.5 year and an average of 19 months, there was no recurrent bleeding and no hepatic encephalopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Esophageal and Gastric Varices↗

Oxalate transport via the sulfate/HCO3 exchanger in rabbit renal basolateral membrane vesicles.

We evaluated the mechanism of oxalate transport in basolateral membrane vesicles isolated from the rabbit renal cortex. An outward HCO3- gradient induced the transient uphill accumulation of oxalate and sulfate, indicating the presence of oxalate/HCO3- exchange and sulfate/HCO3- exchange. For oxalate, sulfate, or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, the K1/2 value for oxalate/HCO3- exchange was nearly identical to that for sulfate/HCO3- exchange, suggesting that both exchange processes occur via the same transport system. This was further supported by the finding of sulfate/oxalate exchange. Thiosulfate/sulfate exchange and thiosulfate/oxalate exchange were also demonstrated, but a variety of other tested anions including Cl-, p-aminohippurate, and lactate did not exchange for sulfate or oxalate. Na+ did not affect sulfate or oxalate transport, indicating that neither anion undergoes Na+ co-transport or Na+-dependent anion exchange in these membrane vesicles. Finally, we found that the stoichiometry of exchange is 1 sulfate or oxalate per 2 HCO3-, or a thermodynamically equivalent process. We conclude that oxalate, but not other organic or inorganic anions of physiologic importance, can share the sulfate/HCO3- exchanger in renal basolateral membrane vesicles. In series with luminal membrane oxalate/Cl- (formate) exchange, exchange of oxalate for HCO3- or sulfate across the basolateral membrane provides a possible transcellular route for oxalate transport in the proximal tubule.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗