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Biomedical subjects

J Sung

Publications and source records attributed to J Sung.

At least 37 records · Page 2Linked to original sources

Treatment of Helicobacter pylori infection.

The availability of clinic-based diagnostic tests means that screening for and the eradication of Helicobacter pylori can be done by primary care physicians. However, confusion still exists regarding indication and treatment regimens. It is universally accepted that patients with Helicobacter pylori infection and peptic ulcer disease require eradication therapy. But the benefits of Helicobacter pylori eradication in gastro-oesophageal reflux disease, non-steroidal anti-inflammatory drug-related peptic ulceration, and non-ulcer dyspepsia remain unclear. There is no evidence that the elimination of Helicobacter pylori is beneficial for asymptomatic patients or in preventing gastric cancer. One-week triple therapy with a proton pump inhibitor or ranitidine bismuth citrate in combination with clarithromycin/metronidazole and amoxycillin is the recommended first-line treatment for Helicobacter pylori infection. Problems with patient compliance and the development of antibiotic resistance are the two most important factors to consider when choosing the treatment regimen. The optimal retreatment therapy for treatment failure is still unknown, and quadruple therapy is best reserved for these cases.

Journal Article↗

Recombinant CD40L treatment protects allogeneic murine bone marrow transplant recipients from death caused by herpes simplex virus-1 infection.

Posttransplant infection associated with host immune deficiency is the major cause of nonrelapse mortality of human bone marrow transplant recipients. In a new murine model of posttransplant infection, allogeneic bone marrow transplant recipients were infected with herpes simplex virus-1 (HSV-1) via intraperitoneal inoculation 12 weeks after transplantation. Allogeneic transplant recipients with graft-versus-host disease (GVHD) had significantly increased mortality from HSV-1 encephalitis, with deficiencies of both specific anti-HSV-1 antibody and total serum IgG2a. GVHD mice displayed a Th2 cytokine profile (increased interleukin-4 [IL-4] and decreased interferon-gamma) and decreased lipopolysaccharide (LPS) responses, suggesting that both T-cell and B-cell defects contributed to the impaired production of antibody. Because passive transfer of hyperimmune serum protected mice from HSV-1 infection, we hypothesized that CD40 ligand (CD40L), which induces B-cell maturation, would protect mice from HSV-1 infection. CD40L-treated GVHD mice showed elevated IgG2a levels and increased survival compared with vehicle-treated transplant recipients.

Animals↗

Studies in cranial suture biology: up-regulation of transforming growth factor-beta1 and basic fibroblast growth factor mRNA correlates with posterior frontal cranial suture fusion in the rat.

The mechanisms involved in normal cranial suture development and fusion as well as in the pathophysiology of craniosyostosis are not well understood. The purpose of this study was to investigate the expression of several cytokines--transforming growth factor-beta-1 (TGF-beta1), basic fibroblast growth factor (bFGF), and interleukin-6 (IL-6)--during cranial suture fusion. TGF-beta exists in three mammalian isoforms that are abundant in bone and stimulate calvarial bone formation when delivered locally. Other bone growth factors including basic fibroblast growth factor and the interleukins regulate bone growth and are mitogenic for bone marrow cells and osteoblasts. The involvement of growth factors in the pathophysiology of craniosynostosis is supported by recent genetics data linking fibroblast growth factor receptor mutations to syndromal craniosynostoses. In this experimental study, in situ hybridization was used to localize and quantify the gene expression of TGF-beta1, bFGF, and IL-6 during cranial suture fusion. In the Sprague-Dawley rat, the posterior frontal cranial suture normally undergoes fusion between 12 and 22 days of age, whereas all other cranial sutures remain patent. All in situ analyses of fusing posterior frontal sutures were compared with the patent, control, sagittal sutures. Posterior frontal and sagittal sutures, together with underlying dura, were harvested from rats at 8, 12, 16, and 35 days of postnatal life to analyze posterior frontal suture activity before, during, and after fusion. In situ hybridization was performed on frozen sections of these specimens using DNA probes specific for TGF-beta1, bFGF, and IL-6 mRNA. A negative control probe to IL-6 in the sense orientation was also used to validate the procedure. Cells expressing cytokine-specific mRNA were quantified (in cells positive per 10(-1) mm2) and analyzed using the unpaired Student's t test. Areas encompassing the fibrous suture and the surrounding bone plates were analyzed for cellular mRNA activity. IL-6 mRNA expression showed a minimal rise in the posterior frontal suture at days 12 and 16, with an average count of 10 and 6 cells per 10(-1) mm2, respectively. The sagittal suture remained negative for IL-6 mRNA at all time points. TGF-beta1 and bFGF analyses were most interesting, showing marked increases specifically in the posterior frontal suture during the time of active suture fusion. On postnatal day 8, a 1.5-fold increase in posterior frontal suture TGF-beta1 mRNA was found compared with sagittal sutures (p = 0.1890, unpaired Student's t test). This difference was increased 26-fold on day 12 in posterior frontal suture TGF-beta1 expression (p = 0.0005). By day 35, posterior frontal suture TGF-beta1 mRNA had nearly returned to prefusion levels, whereas TGF-beta1 mRNA levels in the sagittal suture remained low. A similar upregulation of bFGF mRNA, peaking at day 12, was observed in posterior frontal but not sagittal sutures (p = 0.0003). Furthermore, both TGF-beta1 and bFGF mRNA samples with intact dura showed an intense dural mRNA expression in the time preceding and during active posterior frontal suture fusion but not in sagittal tissues. Our data demonstrate that TGF-beta1 and bFGF mRNA are up-regulated in cranial suture fusion, possibly signaling in a paracrine fashion from dura to suture. TGF-beta1 and bFGF gene expression were dramatically increased both in and surrounding the actively fusing suture and followed the direction of fusion from endocranial to epicranial. These experimental data on bone growth factors support the recent human genetics data linking growth factor/fibroblast growth factor receptor deletions to syndromal craniosynostoses. The ultimate aim of these studies is to understand the underlying mechanisms regulating suture growth, development, and fusion so surgeons may one day manipulate the biology of premature cranial suture fusion.

Animals↗

Wound healing is accelerated by agonists of adenosine A2 (G alpha s-linked) receptors.

The complete healing of wounds is the final step in a highly regulated response to injury. Although many of the molecular mediators and cellular events of healing are known, their manipulation for the enhancement and acceleration of wound closure has not proven practical as yet. We and others have established that adenosine is a potent regulator of the inflammatory response, which is a component of wound healing. We now report that ligation of the G alpha s-linked adenosine receptors on the cells of an artificial wound dramatically alters the kinetics of wound closure. Excisional wound closure in normal, healthy mice was significantly accelerated by topical application of the specific A2A receptor agonist CGS-21680 (50% closure by day 2 in A2 receptor antagonists. In rats rendered diabetic (streptozotocin-induced diabetes mellitus) wound healing was impaired as compared to nondiabetic rats; CGS-21680 significantly increased the rate of wound healing in both nondiabetic and diabetic rats. Indeed, the rate of wound healing in the CGS-21680-treated diabetic rats was greater than or equal to that observed in untreated normal rats. These results appear to constitute the first evidence that a small molecule, such as an adenosine receptor agonist, accelerates wound healing in both normal animals and in animals with impaired wound healing.

Adenosine↗

Comparison of histologic diagnosis between stereotactic core needle biopsy and open surgical biopsy.

BACKGROUND: This study correlates the histologic findings of stereotactic core needle biopsy (SCNB) with open surgical biopsy (OSB) and identifies which lesions can be treated definitively based only on the SCNB histology. METHODS: Women who underwent SCNB between July 1, 1993, and January 1, 1969, were identified by retrospective chart review. Mammographic (MGM) lesions found by SCNB to be ductal or lobular hyperplasia with atypia, or carcinoma underwent OSB. When the histologic findings by SCNB were inconsistent with the MGM findings, the lesion also underwent OSB. RESULTS: 799 women underwent SCNB with 96 (12%) of these going on to OSB. MGM findings in the 92 who presented without a palpable mass included microcalcifications (MCS) in 39, mass in 47, MCS and mass in 7, and tissue distortion in 3. One hundred one breast lesions biopsied first by SCNB, then by OSB were correlated histologically. Sensitivity of SCNB is 89%, with a specificity of 94%. Eight-four women (88%) were able to have definitive treatment at time of OSB because of prior SCNB, and 703/799 (88%) of women were spared OSB entirely. CONCLUSION: SCNB accurately identifies benign breast histology and invasive cancers in women with MGM abnormalities, a distinct advantage over fine needle aspiration cytology. SCNB does not reliably identify women with DCIS and invasion. All women with SCNB diagnosis of ductal or lobular atypia should also undergo OSB.

Adult↗

Endovaginal sonography for the diagnosis of upper genital tract infection.

OBJECTIVE: To determine the clinical utility of transvaginal sonography for the diagnosis of upper genital tract infection. METHODS: Fifty-five women who either met the Centers for Disease Control and Prevention's minimal criteria for acute pelvic inflammatory disease or were being seen for non-classic signs of upper genital tract infection were evaluated. During abdominal and endovaginal ultrasound testing, fluid in the cul-de-sac, discrete tubes with or without tubal fluid, multicystic ovaries, and adnexal masses were noted. Upper genital tract infection was confirmed by laparoscopic visualization or histologic or microbiologic evidence of salpingitis of endometritis. RESULTS: The specificity of identifying fallopian tubes with or without intraluminal fluid on ultrasound was 97% (35 of 36); the sensitivity, however, was only 32% (six of 19). Calculated using Bayes theorem and based on a prevalence rate of 50%, the positive predictive value of visualizing fallopian tubes was 91%. The sensitivities associated with the visualization of a multicystic ovary or tubo-ovarian abscess were 42% (eight of 19) and 32% (six of 19), with specificities of 86% (31 of 36) and 97%, (35 of 36), and positive predictive values of 75% and 91%, respectively. Cul-de-sac fluid was associated with low sensitivity (37%; seven of 19), low specificity (58%; 21 of 36), and the lowest positive predictive value (47%). CONCLUSION: Endovaginal sonography has limited clinical utility in the diagnosis of upper genital tract infection due to its low sensitivity.

Endometritis↗

Proportionate reversible decreases in systolic function and myocardial oxygen consumption after modest reductions in coronary flow: hibernation versus stunning.

OBJECTIVES: This study sought to determine whether modest short-term reductions in coronary flow can produce subsequent proportionate reductions in myocardial function and O2 consumption compatible with myocardial hibernation. BACKGROUND: Acute studies indicate that myocardial energy utilization can be downregulated during moderate flow reduction. Whether this apparently beneficial adjustment persists into the reperfusion period is unsettled because most postischemic contractile dysfunction has been presumed to represent stunned or irreversibly injured myocardium. METHODS: Responses of regional myocardial function and O2 consumption were assessed in chronically instrumented dogs after approximately 50% reductions in flow for 2 h (n = 8) or repeated 2-min total coronary occlusions (n = 6). RESULTS: When unrestricted perfusion was restored after sustained partial occlusions, regional function and O2 consumption stabilized at proportionate, systematically decreased levels ([mean +/- SEM] 80 +/- 3.1% and 81 +/- 5.1% of control values, both p < 0.05) and then returned to control values within 24 h. Similar proportionate reductions occurred after as few as five cycles of brief total occlusion (79 +/- 5.1% and 83 +/- 1.6% of control values, both again p < 0.05); these persisted with additional occlusions and then returned to baseline values within 3 h. The absence of irreversible injury was documented histologically in both series. Sham animals (n = 5) showed no changes in regional function or O2 consumption throughout similar experimental periods. CONCLUSIONS: Moderate decreases in coronary flow or repeated brief coronary occlusions can be followed by proportionate reversible reductions in regional systolic function and O2 consumption compatible with the traditional definition of myocardial hibernation. These findings emphasize the complexity of myocardial responses to flow restriction and call attention to limitations in characterizing reversibly hypocontractile myocardium as simply hibernating or stunned.

Animals↗

Studies in cranial suture biology: Part I. Increased immunoreactivity for TGF-beta isoforms (beta 1, beta 2, and beta 3) during rat cranial suture fusion.

The mechanisms involved in normal cranial suture development and fusion as well as the pathophysiology of craniosynostosis, a premature fusion of the cranial sutures, are not well understood. Transforming growth factor-beta isoforms (TGF-beta 1, beta 2, and beta 3) are abundant in bone and stimulate calvarial bone formation when injected locally in vivo. To gain insight into the role of these factors in normal growth and development of cranial sutures and the possible etiology of premature cranial suture fusion, we examined the temporal and spatial expression of TGF-beta isoforms during normal cranial suture development in the rat. In the Sprague-Dawley rat, only the posterior frontal cranial suture undergoes fusion between 12 and 22 days of age, while all other cranial sutures remain patent. Therefore, immunohistochemical analysis of the fusing posterior frontal suture was compared with the patent sagittal suture at multiple time points from the fetus through adult. Whereas the intensity of immunostaining was the same in the posterior frontal and sagittal sutures in the fetal rat, there was increased immunoreactivity for TGF-beta isoforms in the actively fusing posterior frontal suture compared with the patent sagittal suture starting 2 days after birth and continuing until approximately 20 days. There were intensely immunoreactive osteoblasts present during fusion of the posterior frontal suture. In contrast, the patent sagittal suture was only slightly immunoreactive. A differential immunostaining pattern was observed among the TGF-beta isoforms; TGF-beta 2 was the most immunoreactive isoform and was also most strongly associated with osteoblasts adjacent to the dura and the margin of the fusing suture. Since the increased expression of TGF-beta 2 during suture fusion suggested a possible regulatory role, recombinant TGF-beta 2 was added directly to the posterior frontal and sagittal sutures in vivo to determine if suture fusion could be initiated. Exogenously added TGF-beta 2 stimulated fusion of the ectocranial surface of the posterior frontal suture. These data provide evidence for a regulatory role for these growth factors in cranial suture development and fusion. Additionally, the intense immunostaining for TGF-beta 2 in the dura mater underlying the fusing suture supports a role for the dura mater in suture fusion. It is possible that premature or excessive expression of these factors may be involved in the etiopathogenesis of craniosynostosis and that modulation of the growth factor profile at the suture site may have potential therapeutic value.

Animals↗

Laboratory evaluation of acute upper genital tract infection.

OBJECTIVE: To evaluate the diagnostic test characteristics of common tests used to diagnose upper genital tract infection. METHODS: Subjects included women who either met the Centers for Disease Control and Prevention's minimal criteria for acute pelvic inflammatory disease or who had other signs of upper genital tract infection (i.e., atypical pelvic pain, abnormal uterine bleeding, or cervicitis). The subjects were evaluated with a baseline interview, comprehensive laboratory testing, and either an endometrial biopsy or laparoscopy for definitive diagnosis of upper genital tract infection. Patients were considered positive for upper genital tract infection if they had any of the following findings: 1) histologic evidence of acute endometriosis or salpingitis, 2) laparoscopic visualization of purulent exudate in the pelvis without another source, or 3) positive testing for Neisseria gonorrhoeae or Chlamydia trachomatis from the endometrium, fallopian tubes, or pelvis. RESULTS: One hundred twenty women with adequate endometrial samples were evaluated between August 1993 and September 1995. The median age of the study population was 24 years: 38% were white, 52% were smokers, 81% were insured by Medicaid or were uninsured, and 67% were single. Sensitivities for elevated white blood cell count (WBC), erythrocyte sedimentation rate, C-reactive protein, and increased vaginal white blood cells are 57, 70, 71, and 78%, respectively. If any one test is abnormal, the sensitivity is 100% and specificity is 18%. If all four tests are abnormal, sensitivity is 29% and specificity is 95%. CONCLUSION: Testing for increased vaginal white blood cells was found to be the most sensitive laboratory indicator for upper genital tract infection, whereas serum WBC was the most specific. No one diagnostic laboratory test is pathognomonic for upper genital tract infection. Combinations of positive tests can improve diagnostic specificity and positive predictive value, but with a diminution of sensitivity and negative predictive value. Combinations of negative tests can reliably exclude upper genital tract infection.

Acute Disease↗

Choroidal neovascularization secondary to Candida albicans chorioretinitis.

PURPOSE: To study the clinical histories and courses of six patients with choroidal neovascularization secondary to endogenous Candida albicans chorioretinitis. METHODS: The medical records, fundus photographs, and fluorescein angiograms of six patients who developed C. albicans chorioretinitis secondary to candidemia and who subsequently developed choroidal neovascularization in one or both eyes were reviewed. RESULTS: The six patients ranged in age from 18 to 79 years. Four were women and two men; all but one showed evidence of bilateral chorioretinal scarring secondary to C. albicans chorioretinitis. All patients had been treated successfully with systemic antifungal therapy (amphotericin B). Two weeks to two years after the chorioretinitis, choroidal neovascularization developed in one eye (four cases) or both eyes (two cases). The neovascularization on initial examination was subfoveal in four eyes, extrafoveal in three eyes, and juxtafoveal in one eye. Laser photocoagulation was used in four of the eight involved eyes. In these cases, the active choroidal neovascularization was brought under control. In one eye, the patient had submacular surgery for excision of the choroidal neovascular membrane. Final visual acuities ranged from 20/20 to 20/200 in treated eyes and from 20/50 to 20/400 in untreated eyes. CONCLUSION: Choroidal neovascularization is a potential cause of late visual loss in patients who have had C. albicans sepsis and endogenous C. albicans chorioretinitis. Eyes that have chorioretinal scarring from C. albicans chorioretinitis should be watched for the development of choroidal neovascularization. Laser photocoagulation or perhaps surgical excision of the neovascular complex may be of benefit in selected cases.

Adolescent↗

Malignant mixed mesodermal tumors of the ovary.

OBJECTIVE: To review the experience at Women & Infants Hospital and Hartford Hospital of patients with malignant mixed mesodermal tumors of the ovary, and to review the pertinent literature. METHODS: Fourteen cases of malignant mixed mesodermal tumors of the ovary at the two hospitals over a 5-year period were identified through their tumor registries. Demographic data, pathology, treatment, and survival rates were reviewed. RESULTS: The median survival of the patients in our series was 7 months, with 64% dead of disease in 1 year. A review of the pertinent literature indicated median survivals of 6-12 months, with more than 70% of the patients dead of disease at 1 year, despite treatment. CONCLUSION: Further investigation is needed to determine the proper management for malignant mixed mesodermal tumors of the ovary. Meanwhile, current treatment strategies should recognize the present therapeutic limitations, so as not to diminish any further the quality of life for women with this malignancy.

Aged↗

Recruitment and retention of subjects for a longitudinal cancer prevention study in an inner-city black community.

Recruiting and retaining subjects for longitudinal prevention trials is challenging. The inherent difficulties are compounded when the trial is to take place in a low-income minority community, since prevention is a low priority among residents of such communities, and research is viewed with suspicion. We present our experiences in attempting to recruit and retain low-income black women living in inner-city Atlanta for a trial of an educational intervention to promote screening for cancer. The intervention was conducted in the home by trained lay health workers. We found that recruitment was more successful when we recruited directly from the community than when we recruited from the patient registry of a primary health care center. The attrition rate over an 18-month period was high. Among members of the intervention group, those retained in the study tended to be wealthier and better educated and were more likely to be married and employed than those who dropped out. It seems probable that women of lower socioeconomic status found our intervention to be intrusive or burdensome. Among the controls, socioeconomic factors did not discriminate between those who completed the study and those who did not; loss to follow-up in this group was associated only with younger age. In conducting research of this type in low-income minority communities, special attention must be given to issues of recruitment and retention if the validity of the study is to be preserved.

Adolescent↗

Demographic differences in African-American patients with neoplastic lesions detected by flexible sigmoidoscopy.

There is a higher incidence of colorectal cancer in young African-American patients compared with white Americans. This study examines the incidence, demographic pattern, and distribution of neoplastic lesions identified by flexible sigmoidoscopy in an African-American population. A sample of charts was reviewed from an urban gastroenterology practice that serves predominantly African Americans. A total of 455 patients were found who underwent flexible sigmoidoscopy. The sample included 391 symptomatic patients and 64 asymptomatic patients. Two hundred fifty-five patients were < 50 years old and 200 patients were > or = 50 years. More neoplastic lesions were found among older patients (21 patients: 14 with polyps and 7 cancers) than among younger patients (7 patients: 3 with polyps and 4 cancers); the difference of all positive findings between the two groups was significant. However, the cancerous rate for younger patients was not statistically different from that for older patients. These findings suggest that young African-American patients with colorectal symptoms should undergo aggressive approaches to detect cancer early.

Abdominal Pain↗

Distribution of transforming growth factor beta in a two-week-old human embryo.

Using immunohistochemical methods we have investigated the presence of transforming growth factors beta 1, beta 2 and beta 1 precursor in a two-week-old bilaminar human embryo. TGF-beta 1 precursor was seen in both the epiblast and the hypoblast. In contrast to the widespread localization of TGF-beta 1 precursor in the embryo proper, antibodies to the mature TGF-beta 1 peptide localized preferentially to the hypoblast with only weak staining in the epiblast. Staining with antibodies to TGF-beta 2 was generally weak in both the epiblast and hypoblast layers of the embryo proper. These results show that TGF-beta 1 and beta 2 peptides are detectable as early as the second week of human development.

Embryo, Mammalian↗

Complete sequence analyses show that two defective interfering influenza viral RNAs contain a single internal deletion of a polymerase gene.

Defective interfering (DI) influenza viral RNAs arise by internal deletion of progenitor RNAs. By using recombinant DNA cloning and DNA sequence analysis techniques, we have deduced the complete sequence of two such RNAs (L2b and L3), both arising from the same polymerase (P1) gene of WSN influenza virus. We have also partially determined the sequence of the P1 polymerase gene, including the sequence at the point of deletion and the flanking regions. Our sequence study shows the following. (i) Both L2b and L3 arise by a simple deletion in the P1 gene. (ii) L2b and L3 are 683 and 441 nucleotides long, respectively. (iii) The first 413 and 244 nucleotides of the 5' ends of L2b and L3, respectively, are identical to those of the 5' end of the P1 gene. (iv) The last 270 nucleotides of L2b and 197 nucleotides of L3 are the same as those of the 3' end of the P1 gene. (v) The entire sequence of L3 is present in the sequence of L2b. (vi) Both the 5' and the 3' termini, including the transcription stop and poly(A) addition signals of the progenitor P1 gene, are present in both L2b and L3. (vii) The sequences at the deletion point and the flanking region of the P1 gene do not resemble the consensus splicing sequence of spliced mRNA suggesting that a replicational event rather than splicing is involved in the formation of influenza defective interfering RNAs.

Base Sequence↗