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Biomedical subjects

J L Young

Publications and source records attributed to J L Young.

At least 19 recordsLinked to original sources
PubMed2003

Effect of a DNA nuclear targeting sequence on gene transfer and expression of plasmids in the intact vasculature.

Although the use of nonviral vectors for gene therapy offers distinct advantages including the lack of significant inflammatory and immune responses, the levels of expression in vivo remain much lower than those obtained with their viral counterparts. One reason for such low expression is that unlike many viruses, plasmids have not evolved mechanisms to target to the nucleus of the nondividing cell. In the absence of mitosis, plasmids are imported into the nucleus in a sequence-specific manner, and we have shown in cultured cells by transfection and microinjection experiments that the SV40 enhancer mediates plasmid nuclear import in all cell types tested (Dean et al., 1999, Exp Cell Res 253: 713-722). To test the effect of this import sequence on gene transfer in the intact animal, we have recently developed an electroporation method for DNA delivery to the intact mesenteric vasculature of the rat. Plasmids expressing luciferase or GFP from the CMV immediate-early promoter/enhancer and either containing or lacking the SV40 enhancer downstream of the reporter gene were transferred to the vasculature by electroporation. When transfected into actively dividing populations of smooth muscle or epithelial cells, the plasmids gave similar levels of expression. By contrast, the presence of the SV40 sequence greatly enhanced gene expression of both reporters in the target tissue. At 2 days post-transfer, plasmids with the SV40 sequence gave 10-fold higher levels of luciferase expression, and at 3 days the difference was over 40-fold. The presence of the SV40 sequence did not simply increase the rate of nuclear import and expression, since expression from the SV40-lacking plasmid did not increase beyond that seen at day 2, the time of maximum expression for either plasmid. In situ hybridization experiments confirmed that the increased gene transfer and expression was indeed due to increased nuclear localization of the delivered SV40 sequence-containing plasmid. Based on these findings, the ability to target DNA to the nucleus can increase gene transfer in vivo and inclusion of the SV40 sequence into plasmids will enhance nonviral gene delivery.

Animals↗
PubMed2003

Electroporation as a method for high-level nonviral gene transfer to the lung.

To increase the levels of pulmonary gene transfer by nonviral vectors, we have adopted electroporation protocols for use in the lung. A volume of 100-200 microl of purified plasmid DNA suspended in saline was instilled into the lungs of anesthetized mice. Plasmids expressed luciferase, or beta-galactosidase under control of the CMV immediate-early promoter and enhancer. Immediately following delivery, a series of eight square wave electric pulses of 10 ms duration each at an optimal field strength of 200 V/cm were administered to the animals using 10 mm Tweezertrodes (Genetronics, San Diego, CA, USA). The electrodes were placed on either side of the chest, which had been wetted with 70% ethanol. The animals recovered and survived with no apparent trauma until the experiments were terminated at the desired times, between 1 and 7 days post-treatment. Gene expression was detected by 1 day postelectroporation and peaked between 2 and 5 days. By 7 days, expression was back to baseline. By contrast, essentially no gene expression was detected in the absence of electric pulses. Using a beta-galactosidase-expressing plasmid, the distribution of gene expression appeared to be concentrated in the periphery of the lung, but was also present throughout the parenchyma. The primary cell types expressing gene product include alveolar type I and type II epithelial cells. No inflammation or lung injury was detected histologically or by cytokine measurements in lungs at either 1 or 24 h following electroporation treatment. These results provide evidence that electroporation is a safe and effective means for introducing naked DNA into the lung and form the basis for future studies on targeted pulmonary gene therapy.

Animals↗
PubMed2003

A comparison of population-based cancer incidence rates in Israel and Jordan.

Reliable information about comparative cancer incidence in the Middle East has been lacking. The Middle East Cancer Consortium (MECC) has formed a network of population-based registries with standardized basic data. Here the age-adjusted cancer incidences are compared for four populations: Israeli Jews, Israeli non-Jews, Jordanians and the US Surveillance Epidemiology and End Results (SEER) population, for the years 1996-1997 (Israel) and 1996-1998 (other populations). The all-sites rate of cancer is approximately twice as high in Israeli Jews and SEER, compared with Israeli non-Jews and Jordanians. Rates of lung cancer are similar among Israeli Jews and non-Jews and about twice as high as in Jordanians. Childhood leukaemia rates in Jordan are higher than in Israeli Jews, but lower than SEER. Hodgkin lymphoma rates in Israeli non-Jews and Jordanians are similar to SEER, but non-Hodgkin lymphoma rates are lower than SEER. The previous suspicion of higher overall leukaemia and lymphoma rates in Jordan is thus not confirmed.

Adolescent↗
PubMed2001

Cancer registration in the Middle East.

This project signals an advance in cancer registration in the Middle East region. While it is too early to declare a major breakthrough, significant strides have been made toward establishing a basis for reliable information on the cancer burden at a population level and future collaborative efforts in cancer epidemiologic research and prevention.

Humans↗
PubMed2001

The accuracy of SM-HCV rapid test for the detection of antibody to hepatitis C virus.

OBJECTIVE: Conventional tests for antibody to hepatitis C virus (HCV) require considerable time before results are available. The aim of this study is to examine the accuracy of a new quick test (SM-HCV Rapid Test) for the detection of antibody to hepatitis C virus with reference to the well-established third generation enzyme immunoblot assay (EIA-3; Abbott Laboratories, Chicago, IL). METHODS: A total of 290 subjects (100 patients with chronic hepatitis C infections, 95 patients with other chronic liver diseases, 95 healthy subjects) were recruited. Thirty microliters of serum was tested for anti-HCV by SM-HCV Rapid Test according to the manufacturer's instruction. Liver function tests and serum HCV RNA by polymerase chain reaction (PCR) were measured. RESULTS: In the 100 patients positive for anti-HCV by EIA-3, 98 of these patients were also positive for anti-HCV by SM-HCV Rapid Test. In the 95 patients with other chronic liver diseases, 94 samples were negative for anti-HCV by both EIA-3 and SM-HCV Rapid Test. The remaining one patient was positive for anti-HCV by the EIA-3 but negative by the SM-HCV Rapid Test. In the 95 controls, which were negative for anti-HCV by EIA-3, all were also negative for anti-HCV by SM-HCV Rapid Test and HCV RNA by PCR. Using EIA-3 as the gold standard screening test for anti-HCV, the sensitivity and the specificity of SM-HCV Rapid Test were 98% and 100%, respectively. The positive predictive value and negative predictive value of SM-HCV Rapid Test were 100% and 97.9%, respectively. CONCLUSIONS: SM-HCV Rapid Test is a reliable test with high sensitivity and specificity. The anti-HCV result can be available within a very short period of time. It is a useful screening test for anti-HCV.

Adolescent↗
PubMed2001

HLA-B27 expression does not modulate intracellular Chlamydia trachomatis infection of cell lines.

Chlamydia trachomatis is an obligate intracellular pathogen. Infection of susceptible individuals with this bacterium can trigger the development of reactive arthritis, an acute inflammation that is associated with the expression of the class I major histocompatibility antigen, HLA-B27. Other facultative intracellular pathogens, such as Yersinia and Salmonella spp., are also known triggers of reactive arthritis. Previous studies report conflicting results concerning whether the presence of HLA-B27 modulates the infection of cells with these enteric pathogens. In the present study, we have examined whether the expression of HLA-B27 can influence the infection of cell lines with C. trachomatis and also whether the replication of these bacteria is altered in HLA-B27-expressing cell lines. To do this, we have used a sensitive flow cytometric approach. We fixed and permeabilized cells and used fluorescein isothiocyanate-conjugated monoclonal antibody specific for chlamydia lipopolysaccharide to detect intracellular bacteria. The staining pattern obtained closely resembled the intracellular life cycle of chlamydia, with the appearance of brightly staining cells correlating to the microscopic detection of mature inclusion bodies. Moreover, since the percentage of cells that stained with the antibody was proportional to the infectious inoculum used, we were able to use the technique to quantitate the number of infectious organisms recoverable from infected cell lines. An important component of our study was the use of heparin to prevent reinfection of cells and thus enable the infection to be followed from a discrete time point. Our results suggest that HLA-B27 influences neither the infection nor replication of C. trachomatis serovar L2 within cell lines. Consequently, the role of HLA-B27 in the pathogenesis of reactive arthritis may lie downstream of the invasion and replication stages of the triggering pathogenic infection.

Cell Line↗
PubMed2001

Urinalysis and urinary tract infection: update for clinicians.

Dysuria is a common presenting complaint of women and urinalysis is a valuable tool in the initial evaluation of this presentation. Clinicians need to be aware that pyuria is the best determinate of bacteriuria requiring therapy and that values significant for infection differ depending on the method of analysis. A hemocytometer yields a value of > or = 10 WBC/mm3 significant for bacteriuria, while manual microscopy studies show > or = 8 WBC/high-power field reliably predicts a positive urine culture. In cases of uncomplicated symptomatic urinary tract infection, a positive value for nitrites and leukocyte esterase by urine dipstick can be treated without the need for a urine culture. Automated urinalysis used widely in large volume laboratories provides more sensitive detection of leukocytes and bacteria in the urine. With automated microscopy, a value of > 2 WBC/hpf is significant pyuria indicative of inflammation of the urinary tract. In complicated cases such as pregnancy, recurrent infection or renal involvement, further evaluation is necessary including manual microscopy and urine culture with sensitivities.

Female↗
PubMed2001

What information do parents of newborns with cleft lip, palate, or both want to know?

BACKGROUND: The unexpected birth of a baby with a cleft lip and palate (CL/P) is a shocking and traumatic experience, generating anxiety for parents as well as the attendant health care team. Parents frequently leave the hospital with many unanswered questions because health care professionals do not educate them adequately. OBJECTIVE: To determine what information these parents felt was "critical" for them during the immediate newborn period and to determine how the "informer" was perceived during these encounters. DESIGN: Retrospective, self-administered questionnaire. SUBJECTS AND METHODS: Biologic parents of children with isolated CL/P aged 6 years and younger were surveyed. The questionnaire asked parents whether they remembered discussing diagnosis, prognosis, management, home care, and psychosocial issues. Parents were also asked to rank how "critical" it would have been for the "informer" to have discussed certain issues with them during this first day. RESULTS: Parents gave the highest priority to feeding and learning to identify illness in their baby; 95% wanted to be shown all normal aspects of their baby's exam, and 87% wanted to be told that the CL/P was not their fault. Usage of proper terminology to describe abnormal findings and receiving assurance that their child was not in pain were also important. Unfortunately, many parents reported that the informers did not address these issues. CONCLUSIONS: Parents of newborns with CL/P want basic information in the immediate newborn period, especially regarding feeding and recognizing illness. These data suggest that informers are not adequately discussing these issues with parents.

Attitude to Health↗
PubMed2000

The serpin proteinase inhibitor 9 is an endogenous inhibitor of interleukin 1beta-converting enzyme (caspase-1) activity in human vascular smooth muscle cells.

Interleukin-1beta-converting enzyme (ICE, caspase-1) regulates key steps in inflammation and immunity, by activating the proinflammatory cytokines interleukin (IL-)1beta and IL-18, or mediating apoptotic processes. We recently provided evidence for the regulation of caspase-1 activity via an endogenous inhibitor expressed by human vascular smooth muscle cells (SMCs) (Schönbeck, U., M. Herzberg, A. Petersen, C. Wohlenberg, J. Gerdes, H.-D. Flad, and H. Loppnow. 1997. J. Exp. Med. 185:1287-1294). However, the molecular identity of this endogenous inhibitor remained undefined. We report here that the serine proteinase inhibitor (serpin) PI-9 accounts for the endogenous caspase-1 inhibitory activity in human SMCs and prevents processing of the enzyme's natural substrates, IL-1beta and IL-18 precursor. Treatment of SMC lysates with anti-PI-9 antibody abrogated the caspase-1 inhibitory activity and coprecipitated the enzyme, demonstrating protein-protein interaction. Furthermore, PI-9 antisense oligonucleotides coordinately reduced PI-9 expression and promoted IL-1beta release. Since SMCs comprise the majority of cells in the vascular wall, and because IL-1 is implicated in atherogenesis, we tested the biological validity of our in vitro findings within human atheroma in situ. The unaffected arterial wall contains abundant and homogeneously distributed PI-9. In human atherosclerotic lesions, however, PI-9 expression correlated inversely with immunoreactive IL-1beta, supporting a potential role of the endogenous caspase-1 inhibitor in this chronic inflammatory disease. Thus, our results provide new insights into the regulation of this enzyme involved in immune and inflammatory processes of chronic inflammatory diseases, and point to an endogenous antiinflammatory action of PI-9, dysregulated in a prevalent human disease.

Arteries↗
PubMed1999

Cancer among Hispanic children in California, 1988-1994: comparison with non-Hispanic white children.

BACKGROUND: There has been a perception that California Hispanic children have an unusually high cancer incidence rate, but to the authors' knowledge the only information regarding cancer rates in this population has been the tabular data published in reports issued by the California Department of Health Services. The California Cancer Registry has collected data regarding all cancers diagnosed in California since 1988. METHODS: Data regarding all invasive cancers diagnosed in California Hispanic children age <15 years during the 7-year period 1988-1994 were analyzed. Cancers were grouped according to the International Classification for Childhood Cancers. Age-adjusted and age specific incidence rates were compared with the corresponding incidence rates among non-Hispanic white children. RESULTS: Based on available demographic information, the overall incidence rate of cancer was approximately 7% lower among California children classified as Hispanic than among non-Hispanic white children. Hispanic children had higher incidence rates of lymphoid leukemia and gonadal germ cell tumors and a lower incidence rate of astrocytomas and carcinomas than non-Hispanic white children. CONCLUSIONS: These data do not confirm the perception that California Hispanic children have an unusually high cancer incidence rate but there were notable differences between Hispanic and non-Hispanic white children with regard to the incidence rates of certain cancers. The perception may be due in part to the fact that childhood malignancies represented 3.1% of all cancers diagnosed among Hispanics but only 0.5% of all cancers diagnosed among non-Hispanic whites. This is explained by the lower incidence rate of cancer among California Hispanic adults than among non-Hispanic white adults and the difference in the age distribution of the two populations.

Adolescent↗
PubMed1999

T cell responses to heat-shock protein 60: differential responses by CD4+ T cell subsets according to their expression of CD45 isotypes.

We demonstrate that human T lymphocytes proliferate in vitro to highly purified human heat-shock protein 60 (Hu.hsp60). The response to this self Ag was confined to the CD45RA+ RO- T cell subset, with minimal responses by adult CD45RA- RO+ T cells. Experiments using keyhole limpet hemocyanin as a prototypic novel Ag, or tetanus toxoid as a recall Ag, were consistent with the notion that CD45RA+ RO- and CD45RA- RO+ T cell subsets can be designated as naive and memory cells, respectively; thus, responses to Hu.hsp60 were confined to the putative naive subset. In contrast, both CD45RA+ RO- and CD45RA- RO+ T cell populations proliferated to bacterial hsp60 from Mycobacterium leprae, Escherichia coli, or Chlamydia trachomatis. However, only CD45RA- RO+ (memory) T cells responded to a mycobacterial hsp60-derived peptide previously defined as a major bacteria-specific epitope. Experiments with cord blood T cells, which are CD45RA+ RO- and can be considered truly naive, showed that the peptide could elicit responses from naive T cells in vitro; cord blood cells also responded to Hu.hsp60. Since bacterial hsp60 Ags contain both conserved and nonconserved epitopes, we speculate that in vivo challenge with bacterial hsp60 will activate T cells capable of seeing either type of epitope, but only those that see nonconserved epitopes maintain the CD45RA- RO+ memory phenotype. However, T cells recognizing conserved epitopes, while not apparently being recruited to the memory pool, may nevertheless play a role in immunoregulation, particularly in the context of inflammation, when expression of Hu.hsp60 is increased.

Adult↗
PubMed1999

Musculoskeletal rehabilitation and sports medicine. 1. Head and spine injuries.

This self-directed learning module focuses on head, neck, and spine injuries that are frequent occurrences in sporting activity. It is part of the chapter on musculoskeletal rehabilitation and sports medicine in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. The physiatrist must be able to recognize not only the cause of the acute injury but also the functional consequences of the impairment. This article will discuss some of the more common head, neck, and spine injuries in patients engaged in sports activity and will suggest typical management options for these patients.

Accidents, Traffic↗
PubMed1999

Musculoskeletal rehabilitation and sports medicine. 3. Knee and lower extremity injuries.

This self-directed learning module discusses classic concepts and highlights new advances in the diagnosis and management of knee and lower extremity injuries that commonly occur during athletic competition. It is part of the chapter on musculoskeletal rehabilitation and sports medicine in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation.

Adult↗
PubMed1999

Structure and provision of services in Black churches in New Haven, Connecticut.

Historically, Black (or African American) churches have played a central role as a center of religious and political life and also as a provider of human services and a healing community. This article examined the extent to which African American churches in 1 Northeastern urban environment are involved in the delivery of health and human service programs to their communities. It also explored how comfortable Black clergy are in referring their parishioners to the formal mental health system and identified the actual level of referrals. In addition, the analyses considered the individual and organizational characteristics that predict variations in the levels of support services and the likelihood of referral. Analyses revealed that African American churches deliver a broad range of services to the community. More than two thirds of the clergy feel comfortable in making a referral to a mental health agency or professional, and more than half have actually made a referral. Both service delivery and referral levels varied by several clergy and congregational characteristics. The implications of these findings for research and health policy are considered.

Adult↗
PubMed1999

Developments in clergy malpractice: the case of Sanders v. Casa View Baptist Church.

The courts have so far consistently refused to view misconduct by clergy counselors as constituting clergy malpractice. However, they have increasingly come to view it as a breach of fiduciary duty. More recently, they have also begun to differentiate between the secular and religious aspects of clergy counselors' work. The case discussed in this article (Sanders v. Casa View Baptist Church) provides an instructive example from the United States Court of Appeals, Fifth Circuit, in 1998. The court upheld a district court finding, based on a review of trial testimony, that the defendant's counseling work as a whole (and not merely his sexual misconduct itself) was essentially secular in nature. Thus the plaintiff recovered punitive damages for both breach of fiduciary duty and marriage counseling malpractice.

Clergy↗
PubMed1999

Medication adherence failure in schizophrenia: a forensic review of rates, reasons, treatments, and prospects.

Forensic patients with schizophrenia who fail to adhere to prescribed antipsychotic medication risk recidivism, which continues to be a serious concern. It affects all stages of trial proceedings and impacts on the treaters' liability. Although much remains unchanged since the authors reviewed the subject in 1986, significant advances have occurred. A patient's insight can be assessed with greater precision. Risks posed by past noncompliance, substance abuse, and a dysphoric response to medication are more clearly documented. Clinical and laboratory methods for assessing compliance have improved. Major advances in the effective amelioration of adverse effects can be applied to promote adherence. New augmentation strategies enable adequate treatment at lower doses. The development of atypical antipsychotic agents makes compliance easier to achieve and maintain. Other advances apply to the containment of relapse when it does occur. This review organizes the literature documenting these trends for use in both treatment and consultation.

Antipsychotic Agents↗