Biomedical subjects

Joseph Kaplan

Publications and source records attributed to Joseph Kaplan.

11 recordsLinked to original sources

PubMed2006

Pergolide-associated valvular heart disease.

Pergolide is an ergot derivative dopamine agonist used in the treatment of Parkinson's disease and restless legs syndrome. Ergot derivatives are known to be associated with fibrotic conditions, including a carcinoid-like, fibrotic, valvular heart disease (VHD). Recently, pergolide was identified in association with the development of VHD. This article includes a summary of the literature published on pergolide-associated VHD, a description of the potential mechanisms of drug-induced VHD, and the clinical implications for the management of patients taking pergolide.

Dopamine Agonists↗

PubMed2006

Prevalence of restless legs syndrome among native South Americans residing in coastal and mountainous areas.

OBJECTIVE: To determine the prevalence of restless legs syndrome (RLS) in native South Americans and identify the impact of geographic location. PARTICIPANTS AND METHODS: An epidemiological telephone survey of RLS symptoms involving natives from coastal and mountainous areas was performed during July 2, 2004, through September 28, 2004. The process consisted of 2 phases: the creation of the epidemiological instrument and the telephone survey. RESULTS: Five hundred adults, 250 from the mountainous regions and 250 from the coastal region (190 men and 310 women; age range, 25-85 years) were interviewed and subsequently divided on the basis of International Restless Legs Syndrome Study Group criteria into those who had RLS (RLS+ group) and those who did not (RLS- group). Ten (2.0%) had RLS. The overall rate of RLS in adults living in the mountainous region at 2816 m above sea level (3.2% [8/250]) was significantly higher than that for adults living in the coastal region at 4 m above sea level (0.80% [2/250]; P = .002). The mean age of the RLS+ group was 49.5 years (SD, 15.20 years; range, 25-85 years). CONCLUSION: Native South American adults have a prevalence of RLS well below that reported in populations with European ancestry but similar to that in Asian and Turkish populations. Furthermore, in Ecuador, geographic differences were identified in areas of similar population density.

Adult↗

PubMed2005

Influence of maternal-fetal histocompatibility and MHC zygosity on maternal microchimerism.

To investigate the relationship between maternal-fetal histocompatibility and maternal microchimerism, we developed a sensitive quantitative PCR assay for the neomycin resistance gene (neoR), and, in a mouse model system, used neoR as a noninherited maternal allele marker of maternal cells to detect and quantitate maternal microchimerism in tissues of neoR(-/-) N2 backcross progeny of (neoR(+/-))F(1) females mated with neoR(-/-) males. Using this approach, we obtained evidence for the presence of chimeric maternal cells in the brain, spleen, and thymus of all weanling and adult mice so tested. The numbers of chimeric maternal cells present in the spleen did not differ significantly from those in the thymus regardless of age or maternal-fetal histocompatibility. At all ages, brain tissue had higher level of maternal microchimerism than lymphoid tissue in mice MHC identical with their mothers, but the levels were similar in mice MHC disparate with their mothers. The levels of chimeric maternal cells in both brain and lymphoid tissue of mice with homozygous syngenicity and maternal allogenicity were similar, and tended to be higher than tissue-specific levels in mice with either combined maternal-fetal allogenicity or heterozygous syngenicity. Thus, MHC homozygous progeny had higher levels of maternal microchimerism than MHC heterozygous progeny. We conclude that normal mice possess small numbers of maternal cells in spleen, thymus, brain, and probably most other tissues, and that maternal-fetal histocompatibility influences the levels of these cells by mechanisms related to MHC zygosity of the progeny.

Alleles↗

PubMed2005

Sleep deprivation.

The occurrence of chronic sleep deprivation in the population is commonplace. Both duration and quality of sleep are important to assess when evaluating a patient who has sleep complaints. Excessive sleepiness and decreased psychomotor performance have been demonstrated after sleep deprivation. Sleep loss may impact mood, autonomic function, and the immune system. Sleep-deprived adults may have impaired job performance and are prone to motor vehicle accidents. Simple interventions to ensure adequate sleep can help avoid these hazards.

Benzhydryl Compounds↗

PubMed2005

Cord blood house dust mite allergen in newborns: relationship to maternal blood levels of allergen and allergen specific IgG and IgE.

BACKGROUND: House dust mite allergen has previously been detected in the cord blood of some newborns but not others. The factors that affect the presence and levels in cord blood of this and possibly other allergens are unknown. OBJECTIVE: To test the hypothesis that the levels of maternal allergen and allergen specific IgG affect the presence and levels of newborn allergen. METHODS: Enzyme-linked immunosorbent assays were used to measure the levels of house dust mite allergen Der p 1 and Der p 1 specific IgG and IgE in paired blood samples from 98 mothers and full-term newborns. RESULTS: Der p 1 was detected in 27 mothers and 12 newborns. None of the 71 mothers who lacked Der p 1 had Der p 1-positive newborns. When present, cord blood Der p 1 levels correlated with and were approximately one third of Der p 1 levels in maternal blood. Cord blood Der p 1 levels also tended to correlate with maternal blood levels of Der p 1 specific IgG but showed little, if any, correlation with maternal blood levels of Der p 1 specific IgE. CONCLUSIONS: When detectable, the levels of an allergen in the blood of newborns correlate with the levels of that allergen in the blood of their mothers and tend to be related to maternal levels of allergen specific IgG.

Adolescent↗

PubMed2005

Valvular heart disease in patients taking pergolide.

OBJECTIVE: To Investigate the frequency of valvular heart disease in patients taking pergolide. PATIENTS AND METHODS: The medical records of patients seen at the Mayo Clinic in Jacksonville, Fla, between 1998 and 2003 were searched electronically for the word pergolide and the presence of a 2-dimensional echocardiogram. Patients who had not taken pergolide before undergoing echocardlography served as the control group. Echocardiograms were reviewed for the presence of valvular regurgitation. The frequency of valvular disease in patients taking pergolide was calculated and compared with controls. Associations with dosage and years of treatment also were examined. RESULTS: Fifty-five patients made up the pergolide group, and 63 served as controls. When looking at aortic regurgitation (AR) of any degree, 45% of patients in the pergolide group had AR, compared with 21% of controls (P = .006). The frequency of moderate to severe valvular regurgitation in the pergolide group was 11% (95% confidence interval [CI], 4%-22%), 13% (95% CI, 5%-24%), and 13% (95% CI, 5%-24%) for the tricuspid, mitral, and aortic valves, respectively. No statistical difference was identified in the frequency of moderate to severe valvular regurgitation (mitral, tricuspid, or aortic) when compared with controls. There was marginal evidence of an association between a higher daily dosage of pergolide and moderate to severe AR (P = .05). CONCLUSION: The frequency of AR appears to be Increased in patients taking pergolide. Our study suggests that if a cause-effect relationship exists between pergolide and valvular heart disease, it likely occurs at a low but clinically important Incidence and may be associated with dosage.

Adult↗

PubMed2005

Acquisition of Fas resistance by Fas receptor mutation in a childhood B-precursor acute lymphoblastic leukemia cell line, MML-1.

Programmed cell death, or apoptosis, is a physiological means of eliminating unwanted cells and maintaining immune homeostasis. One of the primary mechanisms is the Fas (CD95)/Fas ligand system. Its inactivation in normal cells and malignant cells may be involved in malignant trans-formation and refractory clinical course, respectively. We established a Fas resistant clone and evaluated the molecular basis for its mechanism of resistance. The Fas-sensitive leukemia cell line, MML-1, was established from a child with B-precursor acute lymphoblastic leukemia. A Fas resistant clone, MML-1R, was obtained by co-culture selection with anti-Fas antibody CH-11. Flow cytometry analysis showed both cell lines had equivalent expression of cell surface CD13, 15, 19, 22 and Fas receptor. Western blot analysis revealed equal expression of FADD (Fas-associated death domain protein), caspase-3 and -8. MML-1 was quite sensitive to both CH-11 and etoposide-induced apoptotis. By contrast, MML-1R had similar sensitivity to etoposide but no response to CH-11. Fas receptor mutation analysis showed a heterozygous death domain A --> G point mutation at 1009 bp, causing a switch from glutamine to glycine at amino acid 256. Immunoprecipitation assay showed decreased binding of Fas to FADD. We also found that etoposide bypassed Fas-FADD interaction in MML-1R by activating caspase-8 and caspase-3. These results indicate that Fas resistance can result from mutations of the gene encoding the Fas receptor which result in decreased FADD binding, thereby blocking formation of the death inducing signaling complex. Screening for similar Fas mutations in therapy resistant malignancies would lead to a better understanding of tumorigenesis and recurrence.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Laser Scanning Cytometry for selection of green fluorescent protein transgenic mice using small number of blood cells.

A Laser Scanning Cytometry-based method was developed for identification of transgenic mice expressing green fluorescent protein (GFP) using minute amounts of peripheral blood. The difference between the autofluorescence of cells not expressing GFP and the fluorescence of GFP expressing cells after excitation with Ar-ion laser (wavelength 488 nm) and detection of emitted fluorescent light in the green channel was high enough for unambiguous identification of the GFP expressing mice. The sensitivity of this method was estimated 1:10(4) for detection of rare GFP expressing cells under the conditions used. This sensitivity should be sufficient for many studies on microchimerism. Because of the possibility for relocation of the cells, this method will be particularly useful for characterizing the cells with high GFP expression using other markers of cell phenotype or conventional morphological analysis.

Animals↗

PubMed2004

Association of maternal histocompatibility at class II HLA loci with maternal microchimerism in the fetus.

For investigating the possible influence of maternal-fetal HLA compatibility on maternal microchimerism, DNA samples from blood of 120 maternal-fetal pairs were genotyped at two polymorphic loci: glutathione-S-transferase M1 (GSTM1) and angiotensin-converting enzyme (ACE). Informative pairs (mother heterozygous/fetus homozygous at one of the two loci) were then tested by quantitative real-time PCR for the noninherited maternal allele(s) and genotyped at the HLA-A, B, and C class I loci and/or at the DRB1 and/or DQB1 class II loci. Small numbers of maternal cells were detected in the circulation of 16 of the 30 informative second- and third-trimester fetuses. Comparison with HLA data suggested an association between microchimerism and maternal compatibility at the class II DRB1 and/or DQB1 HLA loci and with the maternal HLA-DQB1*0301 allele. There was no relationship between maternal microchimerism and maternal-fetal HLA compatibility at other HLA loci or with gestational age, fetal anomalies, or red cell or platelet isoimmunity.

Adult↗

PubMed2004

Interferon-gamma sensitizes osteosarcoma cells to Fas-induced apoptosis by up-regulating Fas receptors and caspase-8.

BACKGROUND: Osteosarcoma is the third most frequent neoplasm in adolescents. Although chemotherapy, frequently used in pre- and post-operative settings, has resulted in significant improvement in disease-free survival, some patients show little sensitivity to chemotherapy and alternative therapeutic strategies are needed. Because the Fas ligand/Fas receptor (CD95, APO-1) apoptosis pathway is a potential therapeutic target in osteosarcomas, we examined the effect of IFN-gamma on Fas-induced apoptosis in four osteosarcoma cell lines. PROCEDURE AND RESULTS: As measured by flow cytometry, all cell lines expressed cell surface IFN-gamma receptors, and when cultured for 2 days in the presence of IFN-gamma, all cell lines exhibited a significant increase in expression of Fas receptors. By flow cytometric detection of intracellular fragmented DNA as a marker of apoptosis, all cell lines cultured with either IFN-gamma or anti-Fas antibody (clone CH-11) alone showed only moderate apoptosis, whereas significantly high levels of apoptosis occurred in cells cultured with both IFN-gamma and CH-11. Western blotting analysis also revealed that IFN-gamma caused up-regulation of caspase-8 in all cell lines, but no change in Fas-associated death domain protein (FADD/MORT1) or caspase-3. Both caspase-8 and caspase-3 were activated when apoptosis was induced with both IFN-gamma and CH-11. Addition to cultures of z-IETD-fmk, an inhibitor of caspase-8, significantly blocked this apoptosis. CONCLUSIONS: IFN-gamma sensitizes osteosarcoma cells to Fas-induced apoptosis through up-regulation of Fas receptor and caspase-8. Combined immunotherapy with IFN-gamma and either anti-Fas monoclonal antibody or cytotoxic T cells that bear Fas ligand might be a useful adjunctive therapy for patients with osteosarcoma.

Adaptor Proteins, Signal Transducing↗

PubMedDate not supplied

Sleep patterns of cyclic parenteral nutrition, a pilot study: are there sleepless nights?

BACKGROUND: Cyclic home parenteral nutrition (HPN) is 1 of the few medical therapies given during normal nocturnal sleep hours, and it is possible that infusion may alter normal sleep patterns. The aim of this pilot study was to evaluate the sleep patterns of 5 patients receiving HPN. METHODS: An Epworth sleep questionnaire was completed and wrist Actigraph data were collected before admission to the sleep laboratory. Formal overnight polysomnography was then preformed for 3 consecutive nights. The first night served as the acclimatization period. On the second and third nights, patients were randomized to receive either no infusion or infusion of their standard parenteral nutrition. Results were reported as the median and range and were compared with historical aged-matched controls. RESULTS: Five patients (3 women and 2 men) with a mean age of 61 years (40 to 73 years) were studied. Patients had been HPN-dependent for a median of 23 months (4 to 60 months). Patients were receiving HPN because of short bowel syndrome (2), chronic pancreatitis (2), and intestinal pseudoobstruction (1). A 1.5-liter HPN formula, infused over 10 hours, included approximately 25 kcal/kg/d with 30% lipid and 1.0 to 1.5 g/kg/d of protein. All solutions included multiple trace elements and standard multivitamins. During total parenteral nutrition (TPN) infusion, the percent of sleep efficiency was higher than without infusion, 81% versus 72%. Sleep efficiency in age-matched controls was approximately 88%. Sleep latency was longer in patients compared with controls, and longer in patients during infusion than without infusion, 35 versus 28 minutes. During TPN infusion, the percent of stage-1 (2%), stage-2 (52%), slow-wave (24%) and random eye movement (REM) sleep (21%) was similar to values during the night without infusion. Controls had lower slow-wave and REM times. The median Epworth sleep score was 3, which is the normal reported range. CONCLUSIONS: Although sleep quality is reduced in patients receiving HPN compared with aged-matched controls, sleep quality does not seem to be negatively effected by cyclic HPN infusion.

Adult↗