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Biomedical subjects

J Chang

Publications and source records attributed to J Chang.

592 records · Page 33Linked to original sources
PubMedDate not supplied

Structural origins of bulky oxidative DNA adducts (type II I-compounds) as deduced by oxidation of oligonucleotides of known sequence.

Bulky DNA adducts, previously termed type II I-compounds, are detected by 32P-postlabeling following treatment of DNA with several Fenton-type oxygen radical-generating reagents, i.e., mixtures of Fe(II) or Ni(II) and H2O2. In an attempt to characterize the chemical nature and mechanism(s) of formation of these novel adducts, 16 single-stranded deoxyribooligonucleotides (20- and 21-mers) of known sequence were oxidized with Fe(II) or Ni(II) and H2O2, and the products were analyzed by 32P-postlabeling. Eight adducts were obtained reproducibly by oxidation of DNA and test oligonucleotides in a sequence-dependent manner. One major adduct (2) was formed only if the test oligonucleotide contained two adjacent adenine residues. Similarly, adducts 3 and 8 specifically originated in AC and CA sequences, respectively. Adduct 6 required a 5'-C-purine-3' sequence. On the other hand, GN sequences (where N is any normal nucleotide) gave rise to adduct 1, another major product, and adduct 7. Similarly, adducts 4 and 5 were produced by the oxidation of AN sequences. These observations are most readily explained if the oxidation reactions caused intrastrand cross-links between adjacent nucleotides, leading to dimer formation. The observation that adducts 1, 4, 5, and 7 did not require a specific 3'-nucleotide was consistent with the notion that these nucleotides lacked a 3'-base, suggesting the presence of a 5'-->3' purine-sugar cross-linked in the oxidized products. The majority of the lesions came from AA and 5'-purine-N-3' sequences. The effects of Fe(II) and Ni(II) were qualitatively similar; however, higher yields of products were observed with Fe(II) as the catalyst. The definition of the chemical origins of these bulky DNA modifications, which represent a new type of DNA damage, is expected to contribute to a better understanding of the mechanism of metal carcinogenesis and to shed light upon the origins of certain endogenous DNA lesions. Recently, some of the major oxidative DNA adducts characterized here were detected by 32P-postlabeling in the renal DNA of male rats treated with ferric nitrilotriacetate, a known potent prooxidative kidney carcinogen in these animals.

Autoradiography↗
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Higher abnormal leukocyte and lymphocyte counts 20 years after exposure to severe stress: research and clinical implications.

OBJECTIVES: Research suggests that individuals with posttraumatic stress disorder (PTSD) are more likely to develop medical conditions and other stress-related psychiatric disorders. Given these findings and others suggesting that PTSD victims may have altered neuroendocrine and immune systems, the hypothesis that Vietnam veterans with PTSD have abnormally high leukocyte and lymphocyte counts was tested. METHODS: The leukocyte and lymphocyte status of male Vietnam "theater" veterans with current partial posttraumatic stress (N = 286), anxiety (N = 274), and depression disorders (N = 192) were compared with those of Vietnam veterans without these disorders 20 years after military service (N = 2190), controlling for intelligence, race, age, income, education, type of enlistment, Vietnam volunteer status, region of birth, cigarette smoking, illicit drug use, body mass index, and alcohol consumption. Abnormal values were defined using standard laboratory reference ranges. Adjusted mean differences also were compared. RESULTS: Based on the results of two-tailed tests, PTSD-positive veterans are more likely to have adjusted leukocyte (OR = 1.83, p = .04) and T-cell (OR = 1.82, p = .045) counts above the normal range and higher mean adjusted leukocyte (p = .042), lymphocyte (p = .01), T-cell (p = .008), and CD4 cell (p = .027) counts. Those with anxiety disorders have adjusted lymphocyte (OR = 1.68, p = .048) and T-cell (OR = 2.06, p = .011) counts above range. They also have test results indicating reactive delayed cutaneous hypersensitivity (OR = 1.77, p = .006), which suggests the presence of highly sensitized T-cell lymphocytes. Finally, depressed veterans are less likely to have B-cell counts above the reference range (OR = 0.55, p = .006). Results of one-tailed tests further suggest that PTSD-positive men also have abnormally high CD4 and CD8 T-cell lymphocyte counts as well (p < .05). CONCLUSIONS: Our findings suggest that chronic, primarily combat-related PTSD is associated with clinically elevated leukocyte and total T-cell counts. Those with current anxiety also have some of these abnormalities in addition to highly sensitized T-cell lymphocytes. Additional research is needed to specify the mechanisms involved here and to investigate the health risks associated with these findings.

Adult↗
PubMedDate not supplied

Absence of transitory [Ca2+]i flux during early in vitro metacyclogenesis of Trypanosoma cruzi.

The phorbol ester TPA (phorbol 12-myristate 13-acetate) substitutes for CO2 as an agonist for transforming Trypanosoma cruzi epimastigotes to the metacyclic trypomastigote stage in a starvation medium consisting of phosphate buffered saline + 10 mM proline, 10 mM sodium acetate and 0.035% NaHCO3. Since TPA is thought to stimulate protein kinase C by mimicking the activity of the secondary messenger diacylglycerol, the above result suggested that T. cruzi metacyclogenesis could be activated by a Ca(2+)-dependent protein kinase C signal induction pathway. Accordingly, cytosolic calcium flux ([Ca2+]i) in epimastigotes, activated with 5% CO2 or TPA (10(-7) M), was measured with the Ca2+ molecular probe, fluo-3AM. In addition, [Ca2+]i was measured in cells incubated with putative metacyclogenic agonists (e.g. proline, glutamate, bioamines, ionophores and catecholamines). None of the compounds studies, except for EGTA, affected cytosolic Ca2+ levels. Control assays with 11 microM thapsigargin, which mobilizes noncytoplasmic Ca2+ stores by inhibiting endoplasmic reticulum Ca(2+)-ATPase, validated our fluorometric assay procedure. Although thapsigargin significantly increases cytoplasmic Ca2+ fluorescence, it has no effect on transformation. The protein kinase C inhibitors staurosporine, H-7 and HA 1004 were tested for their effect on T. cruzi metacyclogenesis. Low concentrations of staurosporine and HA 1004 significantly elevated Peru strain transformation while H-7 had no effect on Peru strain metacyclogenesis. Inhibitor H-7 did significantly depress CL transformation. The results indicate that induction of T. cruzi metacyclic trypomastigote formation by CO2 and TPA is not accompanied by changes in cytosolic Ca2+ and do not provide supporting evidence for participation of a protein kinase C-mediated phosphoinositide cascade in metacyclogenesis.

Animals↗
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An all porcelain lingual bonded retainer: a case study.

In recent years, resin bonded metal retainers have been used to replace teeth in a conservative manner. In addition, porcelain laminates or veneers have been used in esthetic dentistry on single teeth in areas that previously dictated reductions of tooth structure. This paper describes a method of replacing a missing lower anterior tooth with an all porcelain bonded retainer.

Dental Bonding↗
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Addition of fresh amalgam to existing amalgam: microleakage study.

The purpose of this in vitro study was to determine whether adhesive lining materials reduce microleakage in amalgam restorations, and to observe the degree of microleakage at the interface between freshly placed (new) and existing (old) amalgam. Forty-eight specimens were used in the experimental groups. The materials used to study microleakage in this investigation were: copal varnish, a dentin bonding agent (Clearfil New Bond), and a 4-META adhesive (Amalgambond). No significant difference in microleakage was found at the interfaces between freshly placed and existing amalgam. Significantly less microleakage was noted in specimens using the 4-META adhesive and the dentin bonding agent as compared to specimens in which no lining material was placed. Significantly less microleakage was noted in specimens using the 4-META adhesive compared to specimens using cavity varnish.

Analysis of Variance↗
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Bonding fresh amalgam to existing amalgam: a shear and flexural strength study.

The purpose of this study was to compare the shear and flexural strength obtained when various adhesives or liners were used to bond freshly placed amalgam to existing amalgam. The adhesives used in this study were the following: cavity varnish, 4-META adhesive (Amalgambond), and a dentin bonding agent (Clearfil New Bond). After samples were fabricated, shear bond strengths were determined by using an Instron Testing Machine, and flexural strengths determined using a Material Test System (MTS) testing machine. All test groups produced shear and flexural strengths less than one half of the control group. The dentin bonding agent and the 4-META adhesive produced significantly higher shear and flexural strengths than the test group in which no lining material was used.

Analysis of Variance↗
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Addition of fresh amalgam to existing amalgam utilizing various adhesive liners: a SEM study.

The purpose of this study was to observe the interfaces between (1) dentin and amalgam and (2) freshly placed amalgam and existing amalgam using various adhesive liners. Specimens were randomly assigned to four equal groups for liner placement: Group I--control, no liner used; Group II--copal varnish; Group III--4-META adhesive; Group IV--dentin bonding agent. After liner placement and amalgam replacement, specimens set for 24 hours and were then thermocycled in 0.5% basic Fuchsin dye, sectioned, and SEM analyses performed. Microgaps appeared in a disjointed fashion at the interface between freshly placed and existing amalgam. The 4-META adhesive appeared to establish a bond between amalgam and tooth structure and, thus, diminished the microgap between amalgam and dentin.

Composite Resins↗
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Whole blood viscosity parameters and cerebral blood flow.

This report describes the statistical relationship of several whole blood viscosity parameters and cerebral blood flow (CBF) in 53 consecutive patients and normal controls. Significant correlations were present between CBF and serum fibrinogen (P = .05), hematocrit (P less than .05), and a relationship involving both fibrinogen and hematocrit (P less than .01). We conclude that heightened whole blood viscosity does correlate with decreased cerebral blood flow in the ranges measured in our patients, that both fibrinogen and hematocrit must be taken into consideration in viscosity determinations, and that changes in viscosity may have an important effect on CBF in regions of low flow.

Adult↗
PubMedDate not supplied

Laser in situ keratomileusis enhancement after radial keratotomy.

PURPOSE: To present results of laser in situ keratomileusis (LASIK) enhancement after radial keratotomy (RK). METHODS: Sixteen eyes of 10 patients were treated with LASIK for residual myopia and hyperopia after RK. Mean preoperative spherical equivalent refraction was -3.14+/-3.04 D (range, -6.675 to +6.00 D). Best spectacle-corrected visual acuity was 20/20 in 9 eyes, 20/25 in 6 eyes, and 20/30 in 1 eye. Uncorrected visual acuity was better than 20/40 in only 2 eyes. Patients were followed at 1 day, 1 week, 1, 3, and 6 months, and 1 year. Mean follow-up was 8.3 months (range, 1 to 17 mo). RESULTS: All eyes received one LASIK enhancement. Mean final spherical equivalent refraction was +0.16+/-0.68 D (range, -1.00 to +1.75 D). No eyes experienced any visual loss. Five eyes gained 1 line of best spectacle-corrected visual acuity. Uncorrected visual acuity was 20/20 in 9 eyes, 20/25 in 6 eyes, and 20/30 in 1 eye. Two eyes of one patient had the previous RK incisions open. CONCLUSION: LASIK was an effective treatment for correction of residual myopia and hyperopia after RK.

Adult↗
PubMedDate not supplied

Nontraditional services provided by nonprofit and for-profit hospitals: implications for community health.

In part because of reimbursement changes in the 1980s, hospitals became involved in health promotion and disease prevention activities often to attract patients. Today, these services may have an effect on the burden of disease and on illness prevention in some communities. Given the changes anticipated in healthcare delivery, assessing the scope of these services and integrating them with other private-public efforts is of utmost importance. Here we use a 1993 survey of all 4,977 private medical and surgical hospitals in the United States to determine the scope of disease prevention, health enhancement, and palliative services provided by facility type, geographic location, and institutional ownership. We found that church-operated and other nonprofit hospitals appear to provide a spectrum of palliative and preventive health services both for their patients and those in the local community. Given their apparent scope, these services could have an effect on the burden of disease and on illness prevention in many communities. With major changes anticipated in future healthcare delivery and the recent failures reported for many community health intervention programs, healthcare administrators need to focus on ways to integrate their services with other private and public health efforts. If this could be achieved, then private hospitals could be more successful in serving their local communities and in enhancing the public's health in the new century. This article outlines several basic steps to assist administrators in achieving these goals.

Community Health Planning↗
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Pharmacokinetic evaluation of two human epidermal growth factors (hEGF51 and hEGF53) in rats.

The pharmacokinetic profiles of two iodinated human epidermal growth factors (125I-hEGF51 and 125I-hEGF53) in rats receiving a single intravenous dose have been investigated using three independent bioanalytical techniques. Based on a tetrachloroacetic acid precipitation methodology, hEGF51 and hEGF53 were found to have distribution half-lives of 0.80 +/- 0.2 and 0.80 +/- 0.18 min, and elimination half-lives of 79.8 +/- 24.1 and 77.9 +/- 21.1 min, respectively. Evaluated by immunoprecipitation, distribution half-lives were 0.59 +/- 0.09 and 0.63 +/- 0.15 min, and elimination half-lives were 117.8 +/- 22.9 and 118.7 +/- 38.8 min, respectively. Both precipitation techniques produced similar, parallel plasma concentration-time curves, and there were no significant differences in other calculated kinetic parameters, including clearance and volume of distribution evaluated by either technique. Plasma disposition profiles of both peptides were also confirmed by visualization with SDS-PAGE and autoradiography, and were found to be similar to those generated by tetrachloroacetic acid and immunoprecipitation methods. Thus, three independent methods strongly suggest that both peptides have the same disposition profile, which exhibits a very rapid disappearance rate in the distribution phase followed by a much slower elimination process. These results also indicate that the pharmacokinetic behavior of human epidermal growth factor is not altered by deletion of two amino acids from the carboxyl terminus. In addition, the incubation study suggests that about 23% of the exogenous peptides were associated with red blood cells.

Amino Acid Sequence↗
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An immunochemical mass assay for the direct measurement of creatine kinase MB2.

The isoforms of CK-MB have recently received attention as potential biochemical markers for the early diagnosis of an acute myocardial infarction. A sensitive (analytical sensitivity = 0.2 ng/ml) immunochemical mass assay for the direct measurement of the CK-MB2 isoform has been developed by us. This assay utilizes a specific monoclonal capture antibody directed against the B-subunit of CK-MB and a specific monoclonal antibody conjugate directed against the CK-M + lysine subunit. Owing to the lack of a World Health Organization standard for CK-MB, the percent CK-MB2 values had to be normalized by determining both CK-MB and CK-MB2 in assays which differ only in the specificity of the anti-CK-M conjugate. Thus, a related CK-MB immunochemical mass assay utilizing the identical capture antibody and a specific monoclonal antibody conjugate directed against the CK-M subunit was also developed. Analytical sensitivities of the CK-MB and CK-MB2 assays were determined to be 0.5 ng/ml and 0.2 ng/ml, respectively. Both CK-MB and CK-MB2 levels were determined in 46 hospitalized non-AMI patients and 35 non-hospitalized normal patients. Of the 46 hospitalized non-AMI patients (mean age = 70), 26 percent had either CK-MB and/or CK-MB2 values below the level of sensitivity of the CK-MB or CK-MB2 isoform assays. For patients with CK-MB values between 0.5 ng/ml and 2.99 ng/ml, the percent CK-MB2 values ranged from 35 percent to 97 percent. For patients with CK-MB values between 3.0 ng/ml and 6.5 ng/ml, the percent CK-MB2 values ranged from 23 percent to 72 percent. Similar results were obtained for the non-hospitalized group. This assay appears to be useful in determining the clinical utility of CK-MB2.

Aged↗
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[Research in tropical medicine and primary health care in Peru].

Tropical medicine's fundamental task is to improve health in the tropics. By adopting primary health care strategies, it satisfies the real needs of the population while doing research, improving its effectiveness and social impact. We illustrate this with some examples drawn from our experience, where this potentiation is evident. A sanitary dermatology study, based on health auxiliaries and promoters, encompassed a whole jungle province, with 68,977 km2 and 103,681 inhabitants. It resulted in an excellent relationship with the populations, and findings of significance for early diagnosis and control of hanseniasis and other diseases. It also facilitated an extension of activities to include the entire Amazonian Region, with specific concentration on training of the health personnel. Clinico-epidemiological studies on leishmaniasis in Andean valleys incorporated activities of sanitary education, health care, aspects of community development, etc., and extended into other geographic areas. Migrant workers from high-altitude communities in Cusco who have been to the jungle and acquired cutaneous or mucocutaneous leishmaniasis formed Patient Associations. The latter now receive support for their health and development needs from health authorities and many institutions; our Institute contributes with improved therapeutic procedures and further epidemiologic studies to orient preventive and control measures.

Humans↗
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Treatment of lymphoid cell malignancy with In-114m labelled autologous lymphocytes.

This paper is a preliminary report of a clinical trial for the treatment of patients with refractory chronic lymphocytic leukaemia, using autologous In-114m-labelled lymphocytes. Fourteen patients have been treated so far with doses ranging from 69 to 211 MBq. All patients had progressive low grade NHL, resistant to chemotherapy and conventional radiotherapy. Following the intravenous administration of radiolabelled autologous lymphocytes 53% (range 33-92%) of the activity accumulated in the spleen, 35% (21-64%) in the liver and 5% in the bone marrow. The initial response in all patients was a rapid decrease in lymphocyte count in peripheral blood. 10 of the 14 (72%) patients showed a response to the treatment. In 2 patients, there was a complete response which lasted 24 and 36 months respectively, 8 patients showed a partial response of 2 to 17 months duration. None of the patients experienced any subjective toxicity although myelosuppression was seen in all patients. This is a novel concept for the administration of therapeutic radiation in a selective way for the treatment of lymphoid cell malignancy and has produced significant antitumour effect in patients with highly resistant disease. The trial is ongoing and a full report will be published on its completion.

Aged↗
PubMedDate not supplied

Portable cardiopulmonary support system as a bridge to left ventricular assist system implantation. A new strategy for the treatment of end stage cardiac disease.

The key to the successful implantation of a left ventricular assist system (LVAS) for patients with end stage cardiac disease is whether the functions of other vital organs are irreversibly damaged or not. The portable cardiopulmonary support system (PCPS) is not only as convenient as, but is more powerful than, the intra-aortic balloon pump (IABP) in resuscitating impaired end organ function. To investigate the efficacy of PCPS in end stage cardiac disease, end organ function before and after the application of PCPS was retrospectively analyzed for end stage cardiac disease. From 1992 to 1996, five cardiomyopathy patients with deterioration in end organ function, despite application of IABP, underwent PCPS support before implantation of LVAS. Urine volume and levels of liver enzymes (sAST and sALT) and serum creatinine were determined before and after institution of PCPS. After the start of PCPS, the urine output increased significantly (1,840 +/- 450-4,340 +/- 470 ml/day, p < 0.01), and levels of sAST, sALT, and serum creatinine decreased significantly (630 +/- 220-150 +/- 50 IU/L, 630 +/- 260-260 +/- 130 IU/L, and 2.9 +/- 0.5-1.2 +/- 0.1 mg/dl, respectively; p < 0.05). All five patients were successfully bridged to LVAS implantation, and none died of multiple organ failure caused by pre-existing cardiac failure. These results indicate that PCPS before LVAS implantation is useful in resuscitating impaired end organ function and improving the survival rate with LVAS implantation for end stage cardiac disease.

Adult↗