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Biomedical subjects

M Y Chen

Publications and source records attributed to M Y Chen.

At least 55 records · Page 3Linked to original sources

Hydroxychloroquine sulphate inhibits in vitro apoptosis of circulating lymphocytes in patients with systemic lupus erythematosus.

The serological hallmark of systemic lupus erythematosus (SLE) is the presence of antibodies against double-stranded DNA. However, several studies have suggested that it is not DNA itself, but nucleosomes that are the immunogenic particles involved both in the induction of anti-DNA antibodies, and in the pathophysiology of SLE. Meanwhile, It has been demonstrated that there is an accelerated in vitro apoptosis of lymphocytes from patients with SLE. Therefore, one can postulate that the process of apoptosis may provide a source of nuclear antigens to drive the autoantibody response seen in SLE. Our study has demonstrated that hydroxychloroquine exhibits an anti-apoptotic action and this anti-apoptotic effect is dependent on monocyte coexistence. We used both morphology assessment and fluorescent antibody cell sorter (FACS) analysis to measure the apoptotic percentage of lymphocytes from 25 SLE patients in medium alone (control) or with the addition of different concentrations of hydroxychloroquine. Our results have shown that there is a significant decrease in the percentage of apoptosis at the therapeutic concentration (10(-6) M) as compared with the control (p < 0.05). It has been reported that the anti-rheumatic properties of hydroxychloroquine result from its interference with antigen processing in macrophages and other antigen-presenting cells. We propose that this results in decreased stimulation of autoreactive lymphocytes reactive with self-peptides, and consequently diminution of activation-induced cell death (apoptosis) of mature peripheral lymphocytes.

Acridine Orange↗

[Morphologic survey of temporomandibular joint an autopsy investigation].

OBJECTIVES: Understanding the functional structure of temporomandibular joint (TMJ) will be advantageous for us to study the relationship between the occlusal movement and its morphology, and it also will be beneficial for operators of arthroscopy to grasp the relationship between the scope of operation and adjacent landmarks. METHODS: We dissected and measured the TMJ of seven cadavers to study the sizes of condyle and fossa, the oblique angles of their bevel faces and the oblique angles of bevel face of condyle with disc, the distances from midpoint of posterior tragus and cartilage of external auditory canal to the anterior and posterior recess walls. RESULTS: The parameters of the anatomic relationship between condyle, disc, fossa, superior joint space of TMJ and adjacent landmarks were recorded. CONCLUSION: (1) Articular disc coordinates condyle and articular fossa, and increases the condyle anterior bevel's slope which makes them more stable; (2) Transverse ridge of condyle contacts with fossa on point and plane which make lateral motion of condyle more agile; (3) It is important parameter for an operator of arthroscopy to control the depth and range of puncture that measured the distances between anterior and posterior recess walls of upper space in TMJ, the distances from anterior and posterior recess walls to midpoint of posterior tragus and cartilage of external auditory canal, and the size of fossa; Morphology of TMJ is changing with age.

English Abstract↗

Restoration of cellular immunity against tuberculosis in patients coinfected with HIV-1 and tuberculosis with effective antiretroviral therapy: assessment by determination of CD69 expression on T cells after tuberculin stimulation.

Whether immunity against opportunistic pathogens can be fully restored by control of HIV-1 replication remains open to question. This longitudinal study was conducted to measure anti-tuberculosis (TB) cellular immunity in 13 HIV-1/TB-coinfected patients effectively treated by highly active antiretroviral therapy (HAART) in a period of 12 months. In this study, anti-TB cellular immunity was assessed by determining the frequencies of CD 69 expression on CD4+ and CD8+ T cells in response to purified protein derivative (PPD) stimulation (abbreviated as %CD4+CD69 to PPD and %CD8+CD69 to PPD). Here, we show that %CD4+CD69 to PPD correlated with the results of tuberculin skin tests and interferon-gamma (IFN-gamma) production from PPD-stimulated CD4+ T cells, and %CD8+CD69 to PPD also correlated with CD8+ T cell-mediated PPD-specific cytolysis. In overall analysis for these 13 patients, both %CD4+CD69 to PPD and %CD8+CD69 to PPD increased significantly during the 12 months (p =. 003 and p <.001, respectively). However, we found %CD4+CD69 to PPD or %CD8+CD69 to PPD failed to increase substantially in some patients (i.e., immunologic nonresponders). A significantly higher proportion of patients whose baseline CD4+ count was <50 cells/mm3 were considered to be CD4+ nonresponders compared with those whose baseline CD4+ count was >50 cells/mm3. Furthermore, baseline CD4+ cell count in nonresponders is significantly lower than that in responders, although the effectiveness of HAART did not differ between them. Our results indicate that PPD-specific frequencies of CD69 expression may be used as surrogate markers of anti-TB cellular immunity. By this method, we show that full reconstitution of anti-TB cellular immunity in HIV-1/TB coinfected patients may not necessarily be achieved by "successful" HAART and may be influenced by the baseline immune status when HAART is started. These data suggest that the decision to discontinue secondary prophylaxis for opportunistic infections should be cautiously made, even when the CD4+ cell count has significantly increased.

AIDS-Related Opportunistic Infections↗

Clinical spectrum, morbidity, and mortality of acquired immunodeficiency syndrome in Taiwan: a 5-year prospective study.

The clinical spectrum of AIDS and changes of morbidity and mortality associated with HIV infection following initiation of highly active antiretroviral therapy (HAART) are rarely described in the less developed countries in the Asia-Pacific region. We prospectively observed on a follow-up basis 309 HIV-infected patients (82.8% with AIDS) at National Taiwan University Hospital in Taiwan, where highly active antiretroviral therapy (HAART) has been provided to all patients at no charge at any stage of HIV infection since April 1, 1997, to describe the spectrum of HIV-associated opportunistic diseases and evaluate changes of morbidity and mortality from June 24, 1994 through June 23, 1999. Of the patients, 59.3% at study entry had a CD4+ lymphocyte count of <50 cells/microliter. The five leading HIV-associated opportunistic infections included oroesophageal candidiasis (195 patients), Pneumocystis carinii pneumonia (93), tuberculosis (77), mucocutaneous herpes simplex infection (74), and cytomegalovirus diseases (73). The incidence rates of seven major AIDS-defining opportunistic diseases were declining though the changes of the relative proportions varied. The median duration of hospitalization decreased from 36 days in 1995 to 12 days in 1999 (p =.0001). Overestimated mortality rate declined from 148.4 per 100 patient-years in 1995 to 7.4 per 100 patient-years in 1999 (p =.0001) whereas the underestimated mortality rate declined from 110.5 to 5.39 per 100 patient-years (p =.0001). Risk ratio (RR) for mortality in patients who received HAART compared with those who did not was 0.410 (95% confidence interval [CI], 0.249-0.674; p =.0004) and the RR was 0.250 (95% CI, 0.127-0.492; p =.0001) when the analysis was limited to patients with an initial CD4+ lymphocyte count <100 cells/microliter and follow-up duration >30 days after adjusting for their age, gender, type of risk behavior, and CD4+ lymphocyte count. Morbidity and mortality were declining with each study year even in a population consisting mainly of patients at the advanced stage of HIV infection in Taiwan. Earlier diagnosis, accumulation of clinical experience, and use of HAART were associated with lower mortality rates.

AIDS-Related Opportunistic Infections↗

The gene encoding the mitogen-responsive phosphoprotein Dab2 is differentially regulated by GATA-6 and GATA-4 in the visceral endoderm.

Gene targeting studies have demonstrated that the zinc finger transcription factor GATA-6 lies upstream in a transcriptional cascade that controls differentiation of the visceral endoderm. To understand the function of GATA-6 in the visceral endoderm and to identify genes regulated by GATA-6 in this tissue, subtractive hybridization was performed using template cDNAs derived from differentiated wild-type embryonic stem (ES) cells and GATA-6(-/-) ES cells, respectively. These analyses revealed that the gene encoding Dab2, a mitogen-responsive phosphoprotein, is differentially expressed in wild-type and GATA-6-deficient ES cells. Consistent with these findings, Dab2 is expressed in the visceral endoderm of wild-type embryos but not in the visceral endoderm of GATA-6-deficient embryos. Cotransfection experiments demonstrate that the human Dab2 promoter can be transactivated by forced expression of GATA-6 in NIH-3T3 cells. In contrast, forced expression of GATA-4 does not transactivate the human Dab2 promoter and Dab2 is expressed in the visceral endoderm of GATA-4 null embryos. Surprisingly, the specificity of GATA-6-induced transactivation of the Dab2 promoter is not mediated through its zinc finger DNA-binding domain. Taken together, these data demonstrate that the mitogen-responsive phosphoprotein Dab2 is a downstream target of GATA-6 in the visceral endoderm. Moreover, these data demonstrate that molecular mechanisms have evolved that direct, and distinguish, the functional specificity of GATA family members when they are developmentally coexpressed.

3T3 Cells↗

FDG PET evaluation of head and neck cancer: value of imaging the thorax.

BACKGROUND: Patients with primary tumors of the head and neck have been reported to have a high rate of synchronous primary tumors of the upper aerodigestive tract. This study was performed to determine whether inclusion of the thorax in the scan volume would be diagnostically useful for positron emission tomography (PET) with [F-18] fluorodeoxy-D-glucose (FDG) in patients with primary tumors of the head and neck. METHODS: FDG PET scans from the midcranium to the diaphragm were obtained on 56 patients with a variety of head and neck tumors on initial examination before definitive therapy. PET findings in the chest were correlated with results of all other imaging studies, biopsy results, and clinical follow-up. RESULTS: In nine studies (16%), areas of increased FDG uptake in the chest were seen and were judged to be tumors. Six of these probably were false-positive results, although one of these six may have been unconfirmed true positives. Of the three confirmed true-positive studies, two were obvious from other routine studies. In only one case did the PET study reveal a significant lesion not found by means of routine evaluation, resulting in a case-finding yield of 2%. If the unconfirmed possible true-positive results are included, the case-finding yield increases to 4%. CONCLUSIONS: No compelling indication was seen for including the chest in PET studies of patients with head and neck cancer.

Adult↗

Endoscopy in acquired immunodeficiency syndrome patients with diarrhea and negative stool studies.

BACKGROUND: Diarrhea is a frequent gastrointestinal symptom in patients with acquired immuno-deficiency syndrome (AIDS) and is a major source of morbidity and mortality. A stepwise diagnostic approach is often recommended to search for treatable causes. However, whether the stepwise diagnostic approach is adequate for planning treatment and whether specific treatment for infectious etiologies will affect the survival of patients with AIDS remain unknown. METHODS: From March 1996 to September 1997, endoscopy was performed in AIDS patients with diarrhea, the etiology of which was not identified by noninvasive methods. Specific treatment was given according to the identified etiologies and symptomatic treatment was given for those without definite diagnosis. The clinical symptoms, signs, and duration of follow-up were recorded and survival patterns were analyzed. RESULTS: Etiologic diagnoses were made in 26 of 40 patients (65%) who underwent endoscopic studies. Amebic colitis and cytomegalovirus colitis were the 2 leading causes of prolonged diarrhea in patients with AIDS. Thirty-five patients (87.5%) recovered after treatment. The difference in survival time after diarrhea between patients whose symptoms resolved after treatment and those who continued to have diarrhea was statistically significant (p < 0.001). CONCLUSIONS: Endoscopic studies were helpful for the diagnosis of prolonged diarrhea in AIDS patients who had negative stool studies and did not respond to 2 weeks of empiric treatment. Specific treatment according to the results of endoscopy may improve survival in these patients.

AIDS-Related Opportunistic Infections↗

CT diagnosis of acute flank pain from urolithiasis.

The use of noncontrast helical CT (NHCT) to assess patients with acute flank pain and hematuria for potential urinary tract stone disease was first reported in 1995. After several years of experience with the technique, sensitivity and specificity of NHCT has proven to be better than intravenous urography for evaluating ureteral stones. NHCT imaging findings for urinary calculi and the differential diagnosis are discussed in this article. Various extraurinary diseases found while using NHCT in searching for stone disease are addressed and illustrated. As experience with the use of NHCT has increased, clinicians have broadened the indications for this technique, which has a lower charge than standard CT, beyond the specific evaluation of urinary colic. This indication creep has increased the number of NHCT examinations ordered. It has also reduced the rate of stone positivity and increased the diagnostic yield for extraurinary disease.

Abdominal Pain↗

Determination of human immunodeficiency virus type 1 subtypes in Taiwan by vpu gene analysis.

The genetic diversity of human immunodeficiency virus (HIV) type 1 (HIV-1) has been characterized mainly by analysis of the env and gag genes. Information on the vpu genes in the HIV sequence database is very limited. In the present study, the nucleotide sequences of the vpu genes were analyzed, and the genetic subtypes determined by analysis of the vpu gene were compared with those previously determined by analysis of the gag and env genes. The vpu genes were amplified by nested PCR of proviral DNA extracted from 363 HIV-1-infected individuals and were sequenced directly by use of the PCR products. HIV-1 subtypes were determined by sequence alignment and phylogenetic analysis with reference strains. The strains in all except one of the samples analyzed could be classified as subtype A, B, C, E, or G. The vpu subtype of one strain could not be determined. Of the strains analyzed, genetic subtypes of 247 (68.0%) were also determined by analysis of the env or gag gene. The genetic subtypes determined by vpu gene analysis were, in general, consistent with those determined by gag and/or env gene analysis except for those for two AG recombinant strains. All the strains that clustered with a Thailand subtype E strain in the vpu phylogenetic analyses were subtype E by env gene analysis and subtype A by gag gene analysis. In summary, our genetic typing revealed that subtype B strains, which constituted 73.8% of all strains analyzed, were most prevalent in Taiwan. While subtype E strains constituted about one-quarter of the viruses, they were prevalent at a higher proportion in the group infected by heterosexual transmission. Genetic analysis of vpu may provide an alternate method for determination of HIV-1 subtypes for most of the strains, excluding those in which intersubtype recombination has occurred.

Amino Acid Sequence↗

Is it necessary to biopsy the obvious?

OBJECTIVE: The radiologist and oncologist are often confident that biopsy will confirm their suspicion of recurrent disease, but a biopsy is performed to confirm the histologic diagnosis before beginning or altering therapy. We have examined data to determine how often the biopsied lesion represents recurrent disease from the primary tumor or is an instance of new cancer, and whether recurrent disease can be predicted. MATERIALS AND METHODS: We reviewed the medical and imaging records of 253 patients who underwent CT-guided biopsy of an abdominal or pelvic lesion between 1993 and 1996. Sixty-nine of the 253 patients had a previously diagnosed primary tumor and were being examined for possible tumor recurrence or metastasis. The images of these 69 patients were analyzed to determine if the pattern of disease was typical of recurrence or metastasis. RESULTS: In 55 of the 69 patients, the pattern was judged to be typical of metastatic or recurrent disease. Biopsy confirmed this suspicion in all 55 patients. In 14 of the 69 patients, the pattern of spread was judged not to be typical of recurrence or metastasis. These 14 patients were found to have a new primary tumor (n = 4), benign processes (n = 2), and recurrences (n = 8). CONCLUSION: Of the patients for whom radiographic findings suggested recurrence, we found no patients in whom a new primary tumor would have been missed if biopsy had been avoided. Data should now be acquired prospectively to determine whether it may be prudent to make treatment decisions on the basis of imaging findings alone, without histologic confirmation.

Abdominal Neoplasms↗

Resection of suprasellar tumors by using a modified transsphenoidal approach. Report of four cases.

Generally accepted contraindications to using a transsphenoidal approach for resection of tumors that arise in or extend into the suprasellar region include a normal-sized sella turcica, normal pituitary function, and adherence of tumor to vital intracranial structures. Thus, the transsphenoidal approach has traditionally been restricted to the removal of tumors involving the pituitary fossa and, occasionally, to suprasellar extensions of such tumors if the sella is enlarged. However, conventional transcranial approaches to the suprasellar region require significant brain retraction and offer limited visualization of contralateral tumor extension and the interface between the tumor and adjacent structures, such as the hypothalamus, third ventricle, optic apparatus, and major arteries. In this paper the authors describe successful removal of suprasellar tumors by using a modified transsphenoidal approach that circumvents some of the traditional contraindications to transsphenoidal surgery, while avoiding some of the disadvantages of transcranial surgery. Four patients harbored tumors (two craniopharyngiomas and two hemangioblastomas) that arose in the suprasellar region and were located either entirely (three patients) or primarily (one patient) within the suprasellar space. All patients had a normal-sized sella turcica. Preoperatively, three of the four patients had significant endocrinological deficits signifying involvement of the hypothalamus, pituitary stalk, or pituitary gland. Two patients exhibited preoperative visual field defects. For tumor excision, a recently described modification of the traditional transsphenoidal approach was used. Using this modification, one removes the posterior portion of the planum sphenoidale, allowing access to the suprasellar region. Total resection of tumor was achieved (including absence of residual tumor on follow-up imaging) in three of the four patients. In the remaining patient, total removal was not possible because of adherence of tumor to the hypothalamus and midbrain. One postoperative cerebrospinal fluid leak occurred. Postoperative endocrinological function was worse than preoperative function in one patient. No other new postoperative endocrinological or neurological deficits were encountered. This study demonstrates the feasibility of using a modified transsphenoidal approach for resection of certain suprasellar, nonpituitary tumors.

Adolescent↗