Biomedical subjects

H K Chang

Publications and source records attributed to H K Chang.

At least 19 recordsLinked to original sources

PubMed1995

Biodistribution of 18F- and 125I-labeled anti-Tac disulfide-stabilized Fv fragments in nude mice with interleukin 2 alpha receptor-positive tumor xenografts.

We evaluated the biodistribution, pharmacokinetics, and generation of catabolites of an 18F- and 125I-labeled anti-Tac disulfide-stabilized Fv fragment (dsFv) in tumor-bearing nude mice. This dsFv is genetically engineered from a murine monoclonal antibody that recognizes the alpha subunit of the interleukin 2 (IL-2 alpha) receptor. Labeling was performed with 18F using N-succinimidyl 4-([18F]fluoromethyl)benzoate or with 125I using the Iodo-Gen method. The immunoreactivities of the radiolabeled anti-Tac dsFv were > 82%. The biodistribution was evaluated (at 15, 45, and 90 min and 6 h) in athymic nude mice (approximately five/group) bearing s.c. tumor xenografts. Cell line A431 served as the IL-2 receptor-negative control tumor, whereas the ATAC4 cell line served as our IL-2 receptor-positive tumor. Animals received injections of 18F-labeled anti-Tac dsFv (0.7-1.4 megabecquerels/1.5-3 micrograms) and 125I-labeled anti-Tac dsFv (0.1-0.4 megabecquerels/0.9-1 microgram). Blood clearance for both preparations was rapid, with < 10% retained in the blood by 15 min. Maximum accumulation in ATAC4 tumors occurred between 45 and 90 min and peaked at a mean of 4.2% injected dose/g (18F) and 5.6% of injected dose/g (125I). At 6 h, the ATAC4 tumors contained 11 times more 18F and 3 times more 125I than did the A431 tumors. The ATAC4 tumor:blood ratios for the 18F and 125I were > 12:1 and > 1.4:1 at 6 h, respectively, whereas the ratios for the antigen-negative A431 tumor were less than 1. The kidneys were the major route of elimination. Catabolites appeared quickly and were identified as [125I]iodide and predominantly N-epsilon-[18F]4-fluoromethylbenzoyl(alpha-N-acetyl) lysine. This is the first study to evaluate the biodistribution of an 18F-labeled Fv fragment in vitro and in vivo. In vivo, the dsFv was taken up rapidly by the kidneys, producing lysine-containing catabolites for 18F-labeled dsFv and [125I]iodide for 125I-labeled dsFv.

Animals↗

PubMed1995

Microangiopathic hemolytic anemia as an initial presentation of metastatic cancer of unknown primary origin.

Microangiopathic hemolytic anemia (MAHA) is a well-documented but rare complication of disseminated cancer; it usually occurs in the late or terminal stage of cancer. We describe a case of metastatic carcinoma of unknown origin in which MAHA was the initial presentation. A 36-year-old woman came to our hospital with lower back pain and progressive exertional dyspnea for 8 weeks. Hemolytic anemia, thrombocytopenia, and leukoerythroblastosis were found on admission. The peripheral blood smear revealed polychromasia, poikilocytosis, and many schistocytes. Bone marrow biopsy disclosed metastatic carcinoma. After careful workup, we failed to find the primary site of cancer. The anemia and thrombocytopenia responded dramatically to combination chemotherapy with 5-fluorouracil, mitomycin C, and cisplatin. This case indicates that metastatic carcinoma should be included in the differential diagnosis in previously healthy patients with MAHA.

Adenocarcinoma↗

PubMed1995

Inhibition of clinical human immunodeficiency virus (HIV) type 1 isolates in primary CD4+ T lymphocytes by retroviral vectors expressing anti-HIV genes.

Gene therapy may be of benefit in human immunodeficiency virus type 1 (HIV-1)-infected individuals by virtue of its ability to inhibit virus replication and prevent viral gene expression. It is not known whether anti-HIV-1 gene therapy strategies based on antisense or transdominant HIV-1 mutant proteins can inhibit the replication and expression of clinical HIV-1 isolates in primary CD4+ T lymphocytes. We therefore transduced CD4+ T lymphocytes from uninfected individuals with retroviral vectors expressing either HIV-1-specific antisense-TAR or antisense-Tat/Rev RNA, transdominant HIV-1 Rev protein, and a combination of antisense-TAR and transdominant Rev. The engineered CD4+ T lymphocytes were then infected with four different clinical HIV-1 isolates. We found that replication of all HIV-1 isolates was inhibited by all the anti-HIV vectors tested. Greater inhibition of HIV-1 was observed with transdominant Rev than with antisense RNA. We hereby demonstrated effective protection by antisense RNA or transdominant mutant proteins against HIV-1 infection in primary CD4+ T lymphocytes using clinical HIV-1 isolates, and this represents an essential step toward clinical anti-HIV-1 gene therapy.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Cisplatin and 5-fluorouracil as neoadjuvant chemotherapy: predicting response in head and neck squamous cell cancer.

In order to prospectively evaluate the efficacy, toxicity and predictive factors of response to neoadjuvant chemotherapy, a total of 120 patients with head and neck squamous cell cancer diagnosed from January 1992 to November 1993 were enrolled in this study. There were 118 male and 2 female patients, with a median age of 51 years (range 30-74 years). The primary sites were the oral cavity (77), oropharynx (15), hypopharynx (25) and larynx (3). Betel quid chewing was habitual in 91% of patients. All patients were previously untreated, and 94% had stage III or IV disease. Chemotherapy was given in two or three courses to 96 patients who were then assessed for response rate and predictive factors. The chemotherapy regimen consisted of cisplatin 100 mg/m2/day on day 1 and 5-fluorouracil (5-FU) 1 g/m2/day intravenous infusion continuously for 4 to 5 days for 4 weeks. The overall chemotherapy response rate was 56%, with a 3% complete response. By univariate analysis, both the T-stage and tumor volume were significant for predicting the response of the primary site. The age, histologic differentiation, tumor location and N-stage were unpredictive for response. The nodal response (43%) was less than that of the primary site (68%). By multivariate analysis, only the tumor volume (> or = 50 cm3) and the presence of nodal metastases were predictive for the combined TN response. Based on the World Health Organization toxicity criteria, 49 patients experienced grade 3 to 4 mucositis, and 24 patients had grade 3 to 4 vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Inhibition of human immunodeficiency virus type-1 by retroviral vectors expressing antisense-TAR.

The human immunodeficiency virus type-1 (HIV-1) Tat activation response (TAR) region is essential for Tat-mediated trans-activation of the HIV-1 long terminal repeat (LTR). The TAR element is present on the 5' and 3' ends of all HIV-1 transcripts and is relatively conserved among different HIV-1 isolates. These properties make it an attractive target for anti-HIV-1 gene therapy strategies. We have constructed a Moloney murine leukemia-based retroviral vector that expresses a chimeric tRNA(iMet)-antisense TAR fusion transcript complementary to the HIV-1 TAR region. The potential of this anti-TAR retroviral vector to inhibit HIV-1 was initially tested by transient transfections with an HIV-1-LTR-Tat expression plasmid into HeLa-CAT cells. Anti-TAR inhibited Tat-mediated HIV-1 LTR-driven CAT reporter gene expression in a dose-dependent fashion. The antisense-TAR vector was then used to transduce the human SupT1 T cell line. Cotransfection of these SupT1 cells with a Tat expression plasmid plus an HIV-1 LTR-CAT reporter plasmid resulted in decreased CAT gene expression in comparison to control transduced SupT1 cells. The antisense-TAR engineered SupT1 cell line was then challenged with HIV-1MN.HIV-1 viral production was inhibited in SupT1 cells transduced with the antisense-TAR retroviral vector. Greater inhibition of HIV-1 was observed with antisense-TAR as compared to antisense-Tat expressing retroviral vector. These observations suggest that antisense-TAR retroviral vectors are potentially useful for clinical anti-HIV-1 gene therapy.

Blotting, Southern↗

PubMed1994

Block of HIV-1 infection by a combination of antisense tat RNA and TAR decoys: a strategy for control of HIV-1.

The tat gene product (Tat) of HIV-1 is an early regulatory protein necessary for viral gene expression and replication. Tat may also play a role as an extracellular protein in both HIV-1 replication and AIDS-associated disorders such as Kaposi's sarcoma. Thus, Tat represents a good target for gene therapy against AIDS. Here we show that when vectors expressing antisense tat RNA are transiently transfected into CD4+ cells, they block about 70% of HIV-1 replication and inhibit the rescue of Tat-defective HIV-1 proviruses by inhibition of Tat protein expression and consequent lack of transcriptional activation of the HIV-promoter. However, antisense tat vectors cannot block the activity of extracellular Tat protein. Another tat inhibitory construct (poly-Tat-activation response; TAR) previously suggested to inhibit HIV-1 transactivation by sequestering the Tat protein, inhibited the activity of extracellular Tat, but like antisense tat RNA did not completely block viral gene expression and replication. These results suggested that one mode of inhibition is not sufficient to block Tat function. However, when the antisense tat and the poly-TAR constructs were combined HIV-1 gene expression was completely blocked (94-98%), suggesting that a combination of inhibitory genes blocking Tat by sequential steps may be a better approach for AIDS gene therapy.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Effects of the human immunodeficiency virus type 1 Tat protein on the expression of inflammatory cytokines.

Increased levels of inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6, have been detected in specimens from human immunodeficiency virus type 1 (HIV-1)-infected individuals. Here we demonstrate that HIV-1 activates the expression of TNF but not of IL-1 and IL-6 in acutely and chronically infected T cells. The increase in TNF gene expression is due to activation of the TNF promoter by the viral gene product Tat. Transactivation of TNF gene expression requires the product of the first exon of the tat gene and is cell type independent. T cells chronically infected with pol-defective HIV-1 provirus constitutively express both Tat and TNF at levels significantly higher (fivefold) than those seen in control cells, and treatment with phorbol myristate acetate greatly enhances Tat expression and TNF production. As TNF can increase the production of IL-1 and IL-6 and these inflammatory cytokines all enhance HIV-1 gene expression and affect the immune, vascular, and central nervous systems, the activation of TNF by Tat may be part of a complex pathway in which HIV-1 uses viral products and host factors to increase its own expression and infectivity and to induce disease.

Animals↗

PubMed1992

Prognosis of thymic carcinoma: analysis of 16 cases.

Primary thymic carcinoma is a rare malignant neoplasm which arises from the thymic epithelium. Between May 1982 and September 1990, 16 patients with thymic carcinomas, diagnosed at Chang Gung Memorial Hospital, were reviewed. Their ages ranged from 19 to 75 years, with a median of 40 years. Males predominated (male to female ratio was 11:5). The most common presenting symptoms were chest pain, cough, body weight loss and dyspnea. No paraneoplastic syndromes were seen. Chest roentgenograms of 15 patients revealed a mediastinal mass, but a definitive diagnosis could not be made until surgery. Adjacent mediastinal tissues were invaded, or adhered to, by all the tumors. Six distinct histologic types were found, squamous cell carcinoma being the most common (seven cases). The primary treatment of surgical resection was attempted in 14 patients, but only in five cases could the tumors be completely resected; two had a biopsy only. Radiotherapy, with or without chemotherapy, given postoperatively, achieved additional local control in seven of the nine partially resected patients (77%). Distant metastasis occurred in nine of 16 patients (56%). Lymph nodes, bone and lung were the most common metastatic sites. Chemotherapy with cisplatin and/or adriamycin-based regimens was given to patients who had distant metastasis, but the responses were unsatisfactory. The overall survival at one, three and five years was 88%, 51% and 31%, respectively. The median survival was 30 months. The median survival of patients with pure squamous cell carcinoma (> 49 months) was superior to that of patients with other histologic types (18 months; p < 0.01).

Adult↗

PubMed1991

A primary mucinous cystoadenocarcinoma of the retroperitoneum.

A case of primary retroperitoneal mucinous cystoadenocarcinoma of the ovarian type in the presence of normal ovaries is reported. The histogenesis of this rare tumor has been uncertain. Special immunohistochemical stains done on our specimen show that the histogenesis of this tumor is most likely from mucinous metaplasia of coelomic mesothelium. Three cases of primary retroperitoneal mucinous cystoadenocarcinoma of the ovarian type have previously been reported in the English literature and are reviewed.

Adult↗

PubMed1991

Resin-bonded fixed partial dentures: a recall study.

A clinical recall program was initiated at the University of Minnesota to evaluate the longevity and factors affecting longevity of resin-bonded fixed partial dentures (FPDs). Of the 49 resin-bonded FPDs evaluated in the clinic, 43 were acid-etched metal, resin-bonded FPDs, four were combinations of resin-bonded and conventional FPDs, and two were composite resin pontics. None of the combination FPDs and one of the two composite resin pontics were judged as failed at the examination. Of the 43 acid-etched metal resin-bonded FPDs, 15 were found to be debonded (failure rate = 34.9%). The average length of service for the 43 FPDs was 47.3 months. The average time of placement to debondment was 33 months for the 15 debonded FPDs. The failure rate for maxillary FPDs and FPDs with two retainers were significantly lower than the failure rate for mandibular FPDs and FPDs with more than two retainers (p greater than 0.05). The clinical significance of the present study was discussed.

Adolescent↗

PubMed1991

Pulsatile pulmonary microvascular pressure measured with vascular occlusion techniques.

The periodic variations of the pulmonary microvascular pressure during pulsatile perfusion were studied in isolated left lower lobes of canine lungs by the arterial occlusion (AO) and double occlusion (DO) techniques. Sixteen AO and eight DO maneuvers evenly distributed within the pump cycle were performed for each of four frequencies: 36, 54, 72, and 90 beats/min. Nearly identical microvascular pressure contours were reconstructed from the AO and DO maneuvers by relocating the measured occlusion pressures in time. These contours lagged behind the pulmonary arterial pressure waveform. Their amplitude decreased from 25 to 14% of the arterial pulse pressure as the pump frequency was increased from 36 to 90 beats/min. The modulus of the pressure transfer function at the site of arterial occlusion decreased as the frequency increased. The phase was negative for all frequencies and it approached -90 degrees for the higher frequencies. Vasoconstriction induced by serotonin resulted in an increase of the magnitude of the AO pressure contour that was nearly proportional to the increase of the pulmonary arterial pulse pressure. In contrast, elevation of the lobar venous pressure to 10 mmHg increased the amplitude of the AO pressure contour, whereas it slightly decreased the pulmonary arterial pulse pressure. These experiments demonstrate that the AO and DO pressures fluctuate markedly during pulsatile perfusion. Their oscillations would be indicative of the pulsatility in the pulmonary microvascular bed.

Animals↗

PubMed1991

A new method to measure nasal impedance in spontaneously breathing adults.

As an alternative to standard rhinomanometric methods, we applied forced oscillations at the mouth in five normal subjects and determined their nasal impedance with a novel method involving flow subtraction. Pressure oscillations of constant amplitude were applied at the mouth of a subject both when the nostrils were open and when they were closed with a noseclip. The airflows measured under the two conditions were subtracted to yield the oscillating nasal airflow at the imposed pressure. The resultant pressure-flow relation defined the nasal impedance of the subject. For frequencies between 3 and 15 Hz, the transnasal pressure-flow relation was well described by a linear lumped parameter model consisting of a resistive and inertial element. Nasal resistance obtained with flow subtraction did not differ significantly from control measurements obtained while the subjects performed the Valsalva maneuver. In contrast, nasal inertance obtained with flow subtraction was approximately twice that obtained with the Valsalva method. The difference between inertances may reflect structural changes in nasopharyngeal dimensions that occur with the Valsalva maneuver. We conclude that the mechanical impedance of the nasal passage may be determined during spontaneous breathing from the response to imposed forced oscillations at the mouth. The noninvasive nature of this method suggests that it may be simpler to implement than traditional rhinomanometric methods.

Adult↗

PubMed1991

Steady and oscillatory transnasal pressure-flow relationships in healthy adults.

The influence of flow characteristics and gas physical properties on nasal resistance (NR) is difficult to ascertain with traditional rhinomanometric methods because the respiratory airflows used in these methods are largely uncontrolled. As an alternative, we used a novel method of rhinomanometry in which an externally generated flow is passed through the nasal passage via a mouthpiece. The transnasal pressure-flow relationships for both quasi-steady and oscillating flows and with different gases were obtained in five healthy adults with this method. For quasi-steady nasal flows the dimensionless pressure losses were largely independent of physical properties of the gas and a function of the Reynolds number (Re) of the flow. Values of NR for quasi-steady flows were largely independent of flow direction for Re up to roughly 3,000 in all five subjects and for Re up to roughly 19,000 in two of the five subjects. Airway collapse occurred in two subjects at Re greater than 3,000, suggesting that the nonrigid segments of the nasal passage contribute to the intersubject variations in NR at high flow rates. Pressure losses associated with oscillating flows measured at frequencies between 1 and 16 Hz were similar to steady flow losses provided that Re was less than roughly 3,000. For Re greater than 3,000 the oscillating flow resistances were affected by the phasic redistribution of flow into compliant segments of the nasal passage. These results indicate that, for flow rates and harmonic frequencies associated with breathing at rest, the nasal passage behaves as a rigid rough-walled pipe in which pressure losses are largely determined by forces relating to viscous friction and convective accelerations.

Adult↗

PubMed1991

A forced perturbation method of assessing pulmonary mechanical function in intubated infants.

Short pulses in airway pressure were used to assess the pulmonary mechanical function of nine infants suffering acute respiratory distress syndrome or bronchopulmonary dysplasia. All patients were intubated, spontaneously breathing, and mechanically ventilated at the time they were examined. The endotracheal tube was disconnected from the ventilator and connected to a mechanical oscillator that produced brief pulses in airway pressure at a rate of two pulses/s. These pulses were applied to the infants airway for 20-30 s, at which time the infant was replaced on the ventilator. The mean airway pressure during the procedure was maintained at the level of the positive and expiratory pressure that was set on the ventilator. Two classes of patients were identified from the pulse response primarily by the presence or absence of a local resonance in the impedance spectra. Similar results were obtained in five other patients who were examined with zero mean airway pressure, suggesting that the pulse response is little influenced by changes in mean lung volume or total lung compliance. Patient classification appeared related to the duration of ventilation therapy and the transition from one class to another was consistent with the development of high peripheral airway resistance and significant volume shunting in the central airways. These results suggest that brief pulses in airway pressure can be used to detect changes in the pulmonary mechanical function of preterm infants that result from long-term ventilation therapy.

Airway Resistance↗

PubMed1991

Single-incision nephroureterectomy combined with transurethral incision of bladder cuff for renal pelvic tumor.

With the extended use of transurethral endoscopic surgery, we modified the conventional nephroureterectomy that usually requires either a very long incision or two separate shorter incisions. From August 1983 to October 1988, 13 cases of renal pelvic tumor in this hospital were treated single-incision nephroureterectomy combined with transurethral incision of the bladder cuff. The advantages of this technique were less surgical time and a decrease in postoperative wound pain. There were no significant complications or local recurrence noted in this series. The proposed indications were urothelial tumors in the renal pelvis and upper ureter without demonstrable metastases. Tumors of an uncertain cell type preoperatively are especially indicated. The details of this technique are described.

Adolescent↗

PubMed1990

Pulmonary lobar vascular resistances during constant and pulsatile flows.

We measured arterial and venous occlusion pressure profiles in left lower lobes of dog lungs perfused in constant flow and pulsatile flow. Initially, pulmonary arterial pressure, flow rate, and venous pressure were recorded during a series of inflow and outflow occlusions effected during constant flow perfusion. The perfusion was then made pulsatile and while keeping the same flow rate, a second series of vascular occlusions was performed. The arterial occlusion pressures measured with the two modes of perfusion were similar. During pulsatile perfusion, the variation in arterial pressure following an arterial occlusion varied with the timing of occlusion in the pressure cycle. The arterial pressure drop could be recovered by selecting the time-averaged pulmonary arterial pressure as the upstream pressure. During both types of perfusion, the venous occlusion curves were similar. The arterial and venous pressure drops were approximately 4.8 mm Hg and 4.2 mm Hg, respectively. We concluded that the longitudinal distribution of pulmonary vascular pressures can be inferred from occlusion measurements obtained in pulsatile flow.

Animals↗

PubMed1990

Pulmonary vascular impedance in microembolic pulmonary hypertension: effects of synchronous high-frequency jet ventilation.

Increased intrathoracic pressure (ITP) during conventional mechanical ventilation may interfere with the adaptation of right ventricular function to pulmonary hypertension. We studied the effects of synchronous cardiac cycle-specific high frequency jet ventilation (HFJV) in 10 anesthetized dogs before and after embolization of the pulmonary artery with 150-200 microns glass beads. The delivery of the jet was synchronized with early systole, late systole, early diastole and late diastole of the cardiac cycle. Right and left ventricular pressures (Prv and Plv) and pulmonary arterial pressures (Ppa) were measured by transducer-tipped catheters and pulmonary blood flow by an ultrasonic flow probe. Right ventricular end-systolic and end-diastolic volumes (rvESV and rvEDV) were estimated from the thermodilution curve obtained with a Swan-Ganz catheter equipped with a fast response thermistor. Pulmonary hypertension caused significant increases in heart rate (89 +/- 7 to 152 +/- 8 beats/min), rvEDV (80 +/- 7 to 131 +/- 23 ml), diastolic transmural Prv (2 +/- 1 to 5 +/- 1 mm Hg), and rv peak dP/dt (652 +/- 151 to 1035 +/- 160 mm Hg/s). The spectrum of pulmonary vascular input impedance was displaced towards higher frequencies, input resistance was increased and characteristic impedance decreased. The latter change contributed to a relative decrease in the pulsatile component of right ventricular power output. Cardiac output remained unchanged (2.1 +/- 0.2 to 1.9 +/- 0.1 L/min, P NS). Non of these measurements was affected by the timing of the increase in ITP to specific instants in the cardiac cycle compared to apneic periods at any level of pulmonary hypertension. We conclude that in acute microembolic pulmonary hypertension 1 degree a decrease in characteristic impedance contributes to the adaptation of right ventricular function to increased afterload and 2 degrees synchronous cardiac cycle-specific HFJV has no detectable hemodynamic effect.

Animals↗

PubMed1990

Vasectomy and non-fatal acute myocardial infarction: a hospital-based case-control study in Seoul, Korea.

One hundred and sixty-three Korean men aged 35-64 who were admitted to a university-affiliated hospital diagnosed for the first time with acute myocardial infarction (AMI) were compared with 326 matched non-AMI patients hospitalized with a diagnosis considered unrelated to vasectomy. When other potentially confounding variables were controlled for, vasectomized men were found to be 2.6 times (adjusted odds ratio) more likely to have had an AMI as compared to the non-vasectomized men (95% CL: 1.1, 6.1). The adjusted odds ratio of AMI for subjects having had a vasectomy less than or equal to 9 years ago was the same as those who had a vasectomy greater than or equal to 15 years (OR = 2.5), although those who had had a vasectomy 10-14 years ago were associated with a higher odds ratio of 4.2. Among those subjects with vasectomies who were also cigarette-smokers and/or hypertensive, the risk of development of AMI increased multiplicatively compared with those with none of these conditions. We suspect that our finding of this positive association may be spurious due to possible bias introduced during selection of controls and during the process of data collection. Cancer patients may have been less likely to undergo an elective surgical procedure such as vasectomy prior to the admission. When multivariate analysis included only controls who were non-cancer patients (N = 241 controls), the adjusted odds ratio between vasectomy and hospitalization for AMI was reduced to 2.1, (95% CL: 0.8, 5.7), which is no longer statistically significant. When the analysis was further limited to only those control subjects admitted with a diagnosis of digestive system problems, the adjusted odds ratio was reduced to close to unity (1.1). Recognizing the importance of the study topic and the fact that all previous epidemiological studies showed no association between vasectomy and cardiovascular diseases, we urge further studies. A historical cohort study in the Korean setting is considered feasible and is recommended.

Adult↗