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Biomedical subjects

D Lehman

Publications and source records attributed to D Lehman.

At least 19 recordsLinked to original sources
PubMed2005

Successful use of oral ganciclovir for the treatment of intrauterine cytomegalovirus infection in a renal allograft recipient.

Congenital cytomegalovirus (CMV) infection occurs in approximately 1% of newborns and is the leading infectious cause of congenital birth defects. Female renal allograft recipients who develop CMV infection during pregnancy are at risk for both graft dysfunction and fetal morbidity. DNA-based analysis of amniotic fluid (AF) from at-risk pregnancies has been suggested as an adjunct/substitute for traditional culture. We have shown that CMV-polymerase chain reaction of AF is a useful diagnostic test for congenital CMV infection. Using this test we diagnosed CMV infection in the fetus of a 30-year-old renal transplant recipient. As termination was not an option for the family, the patient was extensively counseled and treated with oral ganciclovir. This resulted in clearance of the virus from the AF and the delivery of a healthy newborn girl, free of CMV disease. This is the first reported case to our knowledge of successful use of maternal ganciclovir to treat intrauterine CMV infection in a pregnant renal transplant recipient.

Adult↗
PubMed2001

Pattern- and growth-linked cell cycles in Drosophila development.

During Drosophila development the cell cycle is subject to diverse regulatory inputs. In embryos, cells divide in stereotypic patterns that correspond to the cell fate map. There is little cell growth during this period, and cell proliferation is regulated at G2/M transitions by patterned transcription of the Cdk1-activator, Cdc25/String. The string locus senses pattern information via a > 40 kb cis-regulatory region composed of many cell-type specific transcriptional enhancers. Later, in differentiated larval tissues, the cell cycle responds to nutrition via mechanisms that sense cellular growth. These larval cell cycles lack mitoses altogether, and are regulated at G/S transitions. Cells in developing imaginal discs exhibit a cycle that is regulated at both G1/S and G2/M transitions. G2/M progression in disc cells is regulated, as in the embryo, by string transcription and is thus influenced by the many transcription factors that interact with string's 'pattern-sensing' control region. G1/S progression in disc cells is controlled, at least in part, by factors that regulate cell growth such as Myc, Ras and phosphatidylinositol-3-kinase. Thus G1/S progression appears to be growth-coupled, much as in the larval endocycles. The dual control mechanism used by imaginal disc cells allows integration of diverse inputs which operate in both cell specification and cell metabolism.

Animals↗
PubMed2001

An intradermal skin test for determination of immunity to varicella.

AIMS: To evaluate the usefulness of a diluted, inactivated solution of attenuated varicella vaccine in predicting susceptibility to varicella and its correlation with specific antibody titre to varicella. METHODS: In a prospective blinded study, 63 healthy subjects (aged 2-43 years) were studied. Skin test solution was prepared from vials of OKA strain virus which was inactivated by exposure of the vials to room temperature for 10 days; solution was diluted at 1/50 with normal saline and kept at 4 degrees C until used for skin testing. The material was injected intradermally. Serum samples were drawn prior to skin testing and kept at -70 degrees C until analysis for antibody assay by the indirect fluorescent antibody (IFA) method. RESULTS: Forty three patients were IFA antibody positive; 41 of them reacted to the skin test. One of the 20 IFA negative patients reacted to the skin test. Sixteen patients had two serological tests performed, one month apart. Four out of these 16 patients tested negative with the skin test. All four had negative serology on both samples. Six of the 12 IFA positive patients showed a boost in the antibody titre one month after application of the skin test. The specificity and sensitivity of the skin test compared to the IFA assay were both 95%, and the positive and negative predictive values were 97% and 90% respectively. CONCLUSIONS: Results suggest that a varicella skin test prepared using this simple and relatively cheap method is a safe, sensitive, and specific tool by which to assess immunity to varicella.

Adolescent↗
PubMed2001

Myoclonus secondary to the concurrent use of trazodone and fluoxetine.

A 39-y-o male with a history of human immunodeficiency virus infection and depression was admitted for diagnosis and treatment of tuberculosis and pneumocystis carinii pneumonia infections. Prior to admission, he was on 50 mg trazodone every evening for 2 mo for depression. He was admitted with a 2-w history of fever chills and fatigue and on admission had hand tremors which disappeared at rest. Four days post-admission the trazodone dose was increased to 100 mg and 20 mg fluoxetine was initiated. He became increasingly anxious and his hand tremor worsened 3 d after initiation of the regimen. To rule out drug induced tremor, both trazodone and fluoxetine were discontinued and symptoms resolved in 7 d. Clinicians should be aware of the potential for excessive seratonergic activities secondary to trazodone + fluoxetine interactions causing a worsening myoclonus adverse event.

Adult↗
PubMed2000

Phenotypic pattern of B cells in the appendix: reduced intensity of CD19 expression.

UNLABELLED: The lymphoid tissue of the appendix is considered as part of the gut-associated lymphoid tissue (GALT). In order to understand better the immunological significance of the appendix we analyzed the cellular composition of normal and inflamed human appendix tissue by flow cytometer with special attention to expression of the CD19 and CD5 markers on B cells. Cellular analysis was also performed on peripheral and appendical vein blood samples as well as on omentum and peritoneal fluid samples. The study population included seventeen patients aged 2-15 yr. (mean age - 11.5 yr.) undergoing appendectomy. Ten children were diagnosed with acute appendicitis while 7 had a normal appendix. RESULTS: Compared to the peripheral blood, the appendix contained a significantly higher percentage of CD19 cells (47.6% of total lymphocytes versus 15%, p<0.0001), and B1 cells (4.98% of total lymphocytes versus 2.42%, p=0.001). In addition, the intensity of CD19-staining was markedly decreased in the appendix (mean - 395.7), and also in the omentum (mean - 398.2) as compared to peripheral lymphocytes (mean - 497.7, p<0.0001 for both comparison). Comparison between the inflamed and the non-inflamed appendices revealed that the inflamed appendix contained a significantly higher proportion of B1 cells (5.64% of total lymphocytes versus 3.53%, p=0.032), and also a higher B1/b cell ratio (0.13 vs. 0.07, p=0.01). CONCLUSIONS: These results indicate that the appendix tissue contains higher number of B1 (and B) cells compared to the peripheral blood and that these cells play a role in the primary immune response to acute infection/inflammation in the appendix. Appendiceal B cell population is unique in term of CD19 intensity expression on their surface.

Adolescent↗
PubMed1999

Haplosufficiency of the melancortin-4 receptor gene in individuals with deletions of 18q.

The melanocortin-4 receptor (MC4R) is a seven, transmembrane G-protein-coupled receptor whose ligand, alpha-melanocyte-stimulating hormone (alpha-MSH), is a post-translational derivative of pro-opiomelanocortin (POMC). The regulatory pathway, of which MC4R is a part, has become an area of intense interest because of its potential role in obesity. Three studies have identified individuals with dominantly inherited obesity segregating with mutations in the MC4R gene. It has been hypothesized that the mutation found in these subjects resulted in a loss of gene function resulting in obesity due to haploinsufficiency of the MC4R gene. We have been studying the molecular basis of the phenotype of individuals with large deletions of chromosome 18q. Due to its location at 18q21.3, the MC4R gene is hemizygous in approximately one-third of the individuals in our study. If hemizygosity of the MC4R gene results in haploinsufficiency-induced obesity, then individuals with deletions of 18q whose deletions include the MC4R gene should be obese in comparison with those individuals whose deletion does not include the gene. Our data indicate no difference in obesity among those deleted and not deleted for the gene. This supports the hypothesis that the MC4R gene product is haplosufficient and the involvement of MC4R in obesity may reflect a dominant negative effect.

Base Sequence↗
PubMed1998

Increased number of peripheral blood CD34+ cells in lithium-treated patients.

Eight adult patients with bipolar disorder were prospectively examined to find whether lithium carbonate increased their peripheral blood CD34+ haemopoietic stem cells. Following lithium therapy for 3-4 weeks their neutrophil counts increased by a mean of 88% (from 4625 +/- 1350 x 10(9)/l, mean +/- SD pretreatment, to a peak of 8300 +/- 3910 x 10(9)/l). Concommitantly, there was a significant increment in their CD34+ cells (from 0.11 +/- 0.01% to a peak of 0.18 +/- 0.08%). There was a significant correlation between the rise in neutrophil count and that of the CD34+ cells (r = 0.795, P = 0.019). Lithium therapy may be used to mobilize peripheral blood CD34+ cells for marrow transplantation.

Adult↗
PubMed1998

Bulimia: a primary care approach.

More common than anorexia and less easily detected, bulimia typically begins as an effort to control weight. Although the prognosis is better than that for anorexia nervosa, a number of medical complications can arise related to the mode of purging. Some of these complications can have profound deleterious sequelae if not diagnosed and treated.

Adolescent↗
PubMed1996

Biology and therapeutic uses of myeloid hematopoietic growth factors and interferons.

Recent advances in basic science and clinical trials have demonstrated that IFNs and myeloid hematopoietins play crucial roles in host defense against pathogens and immune surveillance. Here we have reviewed the biologic functions of GM-CSF, G-CSF, IFN-alpha and IFN-gamma. For patients with neutropenia resulting from cytotoxic chemotherapy, bone marrow transplantation, congenital agranulocytosis and cyclic neutropenia, therapeutic uses of GM-CSF and G-CSF were reviewed. Application of these growth factors to patient management represents a major contribution of biotechnology to a difficult area of therapeutics in febrile, neutropenic patients. Because IFN-alpha plays crucial roles in antiviral responses, its clinical applications in hepatitis B and C, human papilloma virus, HIV infection and malignancy were discussed. The use of IFN-gamma in bacterial prophylaxis in patients with chronic granulomatous disease was also presented. Advances in clinical applications of IFNs and hematopoietic growth factors serve as a paradigm for further development to investigate the use of other important cytokines in modern therapeutics.

Granulocyte Colony-Stimulating Factor↗
PubMed1996

Race and sex differences in the distribution of cerebral atherosclerosis.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the influence of race, sex, and other risk factors on the location of atherosclerotic occlusive lesions in cerebral vessels. Previous angiographic studies of patients with stroke or transient ischemic attack (TIA) suggest that extracranial atherosclerosis is more common in whites and intracranial disease is more common in blacks. Noninvasive techniques such as duplex ultrasound, transcranial Doppler (TCD), and magnetic resonance angiography (MRA) allow vascular assessment of a more representative proportion of patients than does conventional angiography alone. METHODS: Consecutive patients evaluated at a community hospital for stroke or TIA over a 2-year period were reviewed. Lesions were defined as a 50% or greater atherosclerotic stenosis by angiography, duplex ultrasound, or TCD, or a moderate stenosis by MRA. RESULTS: Whites were more likely than blacks to have extracranial carotid artery lesions (33% versus 15%, P = .001), but the proportion of patients with intracranial lesions was similar (24% versus 22%). Men were more likely to have intracranial lesions than women (29% versus 14%, P = .03). When multivariate logistic regression analysis was used, white race was the only predictor for extracranial carotid artery lesions, and male sex was the only predictor for intracranial lesions. The cause of stroke/TIA was extracranial carotid artery disease in 8% and intracranial disease in 8% of all patients in the study. CONCLUSIONS: The distribution of cerebral atherosclerosis is influenced by race and sex but not by other vascular risk factors. In our patient population, intracranial disease is as common a cause of cerebral ischemia as extracranial carotid disease.

Aged↗
PubMed1995

Characterization of the mammalian YAP (Yes-associated protein) gene and its role in defining a novel protein module, the WW domain.

We report cDNA cloning and characterization of the human and mouse orthologs of the chicken YAP (Yes-associated protein) gene which encodes a novel protein that binds to the SH3 (Src homology 3) domain of the Yes proto-oncogene product. Sequence comparison between mouse, human, and chicken YAP proteins showed an inserted sequence in the mouse YAP that represented an imperfect repeat of an upstream sequence. Further analysis of this sequence revealed a putative protein module that is found in various structural, regulatory, and signaling molecules in yeast, nematode, and mammals including human dystrophin. Because one of the prominent features of this sequence motif is two tryptophans (W), we named it the WW domain (Bork, P., and Sudol, M. (1994) Trends Biochem. Sci. 19, 531-533). Since its delineation, more proteins have been shown to contain this domain, and we report here on the widespread distribution of the WW module and present a discussion of its possible function. We have also shown that the human YAP gene is well conserved among higher eukaryotes, but it may not be conserved in yeast. Its expression at the RNA level in adult human tissues is nearly ubiquitous, being relatively high in placenta, prostate, ovary, and testis, but is not detectable in peripheral blood leukocytes. Using fluorescence in situ hybridization on human metaphase chromosomes and by analyzing rodent-human hybrids by Southern blot hybridization and polymerase chain reaction amplification, we mapped the human YAP gene to chromosome band 11q13, a region to which the multiple endocrine neoplasia type 1 gene has been mapped.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Cartilage oligomeric matrix protein (COMP) is an abundant component of tendon.

An abundant matrix protein was purified under native conditions from adult bovine tendon and identified as cartilage oligomeric matrix protein (COMP) by immunochemical crossreaction, amino acid sequence identity of tryptic peptides derived from both N- and C-terminal regions, and structure revealed by electron microscopy. Immunohistochemistry showed age-dependent differences in distribution of COMP in tendon.

Aging↗
PubMed1994

Pentoxifylline attenuates oxygen-induced lung injury.

Patients requiring mechanical ventilation can develop severe pulmonary injury. Although pentoxifylline (PTX) is known to attenuate endotoxin and tumor necrosis factor (TNF)-induced lung injury, as well as decrease interleukin-6 (IL-6) levels following hemorrhage and resuscitation, it remains unknown if this agent has any beneficial effects against O2-induced lung injury. The aim of this study, therefore, was to determine if PTX attenuates pulmonary oxygen toxicity. To investigate this, male Sprague-Dawley rats were injected subcutaneously with 1 ml saline or 1 ml PTX (50 mg/kg) and immediately exposed to either 21% O2 or > or = 95% O2 for 52 hr. The animals were then reweighed and euthanized. Pleural fluid was collected, blood samples were obtained, and lung lavage was performed. Lactate dehydrogenase (LDH) activity, protein content, and IL-6 concentrations were determined in the lavage fluid and serum. The supernatant LDH activity, protein content, pleural fluid accumulation, and IL-6 concentration were significantly decreased (P < 0.05) in those animals pretreated with PTX prior to exposure to hyperoxia compared to those animals exposed to hyperoxia and not treated. Furthermore, the hematocrit and serum IL-6 concentration were also decreased in the treated group and not significantly different from the controls. Thus, PTX appears to attenuate O2-induced lung injury and may play a role in protecting those patients at risk for developing pulmonary oxygen toxicity.

Animals↗
PubMed1993

Falls from heights: a problem not just in the northeast.

BACKGROUND: Falls from windows and balconies have long been recognized as a health hazard facing children in large, eastern cities. No study has explored this problem in western and sunbelt states. METHODS: A retrospective chart review of children admitted to a large, west coast hospital for injuries sustained secondary to a fall from a building was conducted. The health care costs for injuries secondary to falls were estimated by reviewing Los Angeles County hospital discharge data over a 3-year period. Representative cities in western and sunbelt states were surveyed about their building code regulations for windows and balconies. RESULTS: Ninety-three children fell from windows and 58 from other structures (balconies, fire escapes, and roofs). The fall victims were more likely to be male (male-female ratio, 1.6:1), younger than 3 years old, and playing at the time of the fall. In more than 70% of the cases reviewed, the child fell from a second-story window. Morbidity was significant, with two thirds of children experiencing at least one fracture and more than 30% of the children requiring the intensive care unit. The mortality rate was low (0.7%); however, 10% were left neurologically impaired. The cost for hospitalization was approximately $5000 to $8000 per child. The survey revealed a lack of building code regulations for windows or window guards in western and sunbelt states. CONCLUSIONS: Falls from windows are a significant problem for children, not only in eastern cities, but throughout the nation. Morbidity is significant, even from less than three stories, and the health care cost is high. Preventive strategies are suboptimal.

Accidental Falls↗
PubMed1992

Conjunctive enhancement of enzymatic thrombolysis and prevention of thrombotic reocclusion with the selective factor Xa inhibitor, tick anticoagulant peptide. Comparison to hirudin and heparin in a canine model of acute coronary artery thrombosis.

BACKGROUND: Effective thrombolytic recanalization of an occluded coronary vessel is often limited by acute thrombotic reocclusion, which has galvanized the search for effective adjunctive or conjunctive antithrombotic agents. METHODS AND RESULTS: Recombinant versions of tick anticoagulant peptide (rTAP) and hirudin (rHIR) are highly selective and potent polypeptide inhibitors of factor Xa and thrombin, respectively. The comparative antithrombotic efficacies of rTAP, rHIR, and heparin, administered conjunctively with recombinant tissue-type plasminogen activator (rt-PA), on thrombolytic reperfusion and reocclusion, were determined in a canine model of occlusive coronary artery thrombosis with a superimposed critical stenosis. In this model, a platelet-rich occlusive thrombus was formed after damage to the intimal surface of the left circumflex coronary artery induced by electrolytic injury. Fifteen minutes after occlusion, the dogs received a systemic intravenous administration of either saline (control), heparin (200 units/kg bolus + 2 units/kg/min, heparin (HEP) 200 or 100 units/kg bolus + 1 unit/kg/min, HEP 100), rHIR (50 or 100 micrograms/kg/min, rHIR 50 or 100, respectively), or rTAP (100 micrograms/kg/min, rTAP 100) followed 15 minutes later by rt-PA (100 micrograms/kg bolus + 10 micrograms/kg/min over 90 minutes). Infusions of the conjunctive agents were discontinued 60 minutes after termination of rt-PA. The incidence and time (mean +/- SEM) to thrombolytic reperfusion were determined for control (five of 12; 68.0 +/- 7.8 minutes), HEP 100 (six of eight; 40.1 +/- 8.3 minutes), HEP 200 (six of eight; 39.8 +/- 9.5 minutes), rHIR 50 (six of eight; 51.7 +/- 14.6 minutes), rHIR 100 (eight of eight; 19.5 +/- 4.2 minutes), and rTAP 100 (eight of eight; 22.8 +/- 10.0 minutes). The incidence and time to reocclusion after rt-PA were determined for control (four of five; 45.7 +/- 12.5 minutes), HEP 100 (four of six; 18.2 +/- 10.7 minutes), HEP 200 (five of six; 26.2 +/- 20.7 minutes), rHIR 50 (four of six; 47.3 +/- 21.6 minutes), rHIR 100 (six of eight; 89.8 +/- 5.9 minutes), and rTAP 100 (three of eight; 54.0 +/- 16.3 minutes). All of the dogs that reoccluded in the rHIR 100 group did so after termination of the inhibitor infusion, whereas two of the three dogs in the rTAP 100 group that reoccluded did so during the inhibitor infusion. Coronary artery blood flow was characterized by intermittent periods of reocclusion and recanalization in all groups except rTAP 100. CONCLUSIONS: The potent antithrombotic effects of rTAP in this model directly implicate de novo thrombin formation as a major source of thrombin activity within the highly thrombogenic residual thrombus. These findings suggest that direct inhibition of prothrombinase activity may be an effective strategy in the development of a new class of conjunctive agents.

Animals↗
PubMed1991

Improvement of hepatitis B vaccine by the use of a new adjuvant.

Humoral and cellular immune responses of mice and guinea-pigs to hepatitis B virus surface antigen when alum-precipitated or administered with Syntex Adjuvant Formulation (SAF) were compared. Two doses of HBsAg in SAF were sufficient to elicit antibody responses, and using SAF the dose of antigen could be reduced to one-tenth of that required to elicit antibody responses by alum-adjuvanted HBsAg. The use of SAF increased and made more consistent the antibody responses in young mice and in strains of mice with inherited low responses to HBsAg. Cellular responses to HBsAg were more consistently observed when SAF was used than when alum was used. SAF increased the formation of IgG2a antibodies in mice except in the B10.M strain; antibodies of this isotype activate complement and act synergistically with antibody-dependent effector cells more efficiently than antibodies of other isotypes. If SAF proves acceptable for human use it could improve vaccines against hepatitis B virus.

Adjuvants, Immunologic↗