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Biomedical subjects

J Abrams

Publications and source records attributed to J Abrams.

At least 55 records · Page 3Linked to original sources
PubMed1997

Lymphotactin is produced by NK cells and attracts both NK cells and T cells in vivo.

Injection of lymphotactin (Lptn) into the peritoneum caused an influx of lymphocytes at 24 h. Phenotypic analysis of the cellular influx showed that a large proportion of these cells were T lymphocytes; however, a large number of NK cells was also present. This effect of murine Lptn (mLptn) was specific since the cellular influx was blocked with a mLptn-specific mAb. Similar results were observed when Lptn was injected s.c. and the tissue was analyzed by immunohistochemistry using an anti-CD3epsilon mAb. Microchemotaxis assays confirmed that murine NK cells respond to mLptn, and also showed human NK clones to be similarly responsive to recombinant human Lptn (rhLptn). Immunohistochemical analysis of IL-2-activated murine NK cells and Northern analysis of human NK clones revealed that these cells also produce Lptn, suggesting that a self-regulatory migration mechanism exists in NK cells. Together these data confirm, in vivo, the lymphocyte specificity of Lptn previously observed in vitro and extend its chemotactic effects to the NK cell lineage. We also investigated the functional consequences of truncating the carboxyl terminus of hLptn. This truncated molecule (which is missing the carboxyl-terminal 22 amino acids of hLptn) had no detectable activity on human PBLs. In addition, while hLptn was found to attract murine splenocytes in vitro, the carboxyl-terminal truncated hLptn was again inactive on murine splenocytes. This observation indicates the presence of structural features in the carboxyl terminus of Lptn that are necessary for its biologic activity.

Amino Acid Sequence↗
PubMed1997

Apoptotic frequency is increased in spermatogenic maturation arrest and hypospermatogenic states.

PURPOSE: Increased testicular apoptosis has been observed in maturation arrest and hyposper-matogenesis states in rodent models, but this process has not yet been characterized in humans. We hypothesized that increased cell death present with accelerated apoptosis is significant in pathophysiology of many male infertility states associated with abnormal spermatogenesis. We examined frequency of apoptotic bodies in human testis biopsy specimens from infertile men using morphometric analysis of hematoxylin and eosin stained paraffin sections. MATERIALS AND METHODS: Testis biopsy specimens were obtained for routine clinical purposes from azoospermic and severely oligozoospermic men and were stained with hematoxylin and eosin. Apoptotic bodies were identified using established morphometric criteria. Apoptotic indexes, defined as apoptotic bodies per total number of cells and per Sertoli cells, were calculated after counting all intratubular spermatogenic cells and Sertoli cells in 20 tubules. RESULTS: A total of 51 biopsies was performed in 50 men. Significantly increased apoptotic body per total cell and apoptotic body per Sertoli cell ratios were observed in maturation arrest and hypospermatogenesis states in comparison to Sertoli cell only and normal spermatogenesis (p < 0.05, Mann-Whitney test). CONCLUSIONS: Increased apoptosis in maturation arrest and hypospermatogenesis states compared to normal but obstructed spermatogenesis and Sertoli cell only were observed, indicating a prominent role for this form of programmed cell death in human male infertility.

Apoptosis↗
PubMed1997

Tumoral calcinosis of the triangular fibrocartilage complex: a case report.

A case of calcium hydroxyapatite deposition in the triangular fibrocartilage of the wrist is presented. The deposit took the more unusual form of a tumor, posing diagnostic difficulties. Magnetic resonance imaging was helpful in delineating the lesion, but could not identify its nature. Surgical excision resulted in resolution of symptoms.

Adult↗
PubMed1997

Image analysis assessment of the abnormal testis biopsy in male infertility.

PURPOSE: We previously demonstrated that testis biopsy image analysis is an effective method for quantifying intratubular spermatogenic cells in the obstructed testis with normal spermatogenesis. As an extension of the initial report, we describe using the quantitative ploidy and morphological characteristics of cells counted with image analysis in abnormal testis biopsies obtained for a male infertility evaluation. MATERIALS AND METHODS: Image analysis using a specifically designed filter was performed on Feulgen stained 5 microns, sections of paraffin embedded testicular tissue. Archival testicular tissue had been obtained using standard biopsy techniques from patients with azoospermia or severe oligospermia. Qualitative classification was based on standard evaluation of hematoxylin and eosin processed tissue. RESULTS: There were 62 biopsies performed in 58 men. Significant differences in the intratubular content of haploid (spermatozoa and spermatids), diploid and tetraploid cells were found among the 5 categories of abnormalities: the Sertoli-cell-only syndrome, spermatocyte arrest, spermatid arrest, hypospermatogenesis and normal spermatogenesis. Moderate variability was found in the proportion of cell types in spermatid arrest and hypospermatogenesis. CONCLUSIONS: Testis biopsy image analysis provides a quantitative method for categorizing abnormalities of intratubular cell content present in male infertility states by using deoxyribonucleic acid content and morphology characteristics. The limitations of the present qualitative analysis system are emphasized by the moderate variability evident within the current categories of spermatid arrest and hypo-spermatogenesis states.

Adult↗
PubMed1997

Testis biopsy image analysis effectively quantifies spermatogenic cell types.

PURPOSE: Evaluation of the testis biopsy specimen in male infertility has been hampered by the qualitative rather than quantitative nature of routine histological techniques and interpretation. Although useful, flow cytometry has demonstrated significant limitations due to its inability to differentiate among haploid cell types, spermatozoa and spermatids. Thus, deoxyribonucleic acid image analysis was performed on testis biopsy specimens to combine the advantages of quantitative ploidy and morphological characteristics to develop a more effective quantitative system. MATERIALS AND METHODS: Image analysis using a specifically designed filter was performed on Feulgen stained 5 microns. sections of paraffin embedded testicular tissue. The archival testicular tissue had been obtained using standard biopsy techniques from patients with azoospermia and normal spermatogenesis on routine hematoxylin and eosin processed tissue. RESULTS: The overall findings (mean plus or minus standard deviation) in 20 biopsies from 18 men are haploid 54.2 +/- 5.6, diploid 31.2 +/- 5.2 and tetraploid 15.0 +/- 4.6%. Spermatozoa and spermatids contributed 23.2 +/- 5.7 and 30.9 +/- 7.6% to the total cell content, respectively. A mean of 2,462 +/- 254 cells were counted per case. CONCLUSIONS: We used image analysis to evaluate testicular biopsies. This technique can quantitatively determine the percentages of various cell types within the seminiferous tubules. Furthermore, it can differentiate between spermatozoa and spermatids based on morphological characteristics. This technique, which combines ploidy and cell morphology characteristics, represents a significant advancement in the interpretation of the testicular biopsy, and has implications for redefining the presently used system of qualitative interpretative assessment.

Adult↗
PubMed1997

Racial differences in surgically staged patients with endometrial cancer.

This study examined whether differences in survival for endometrial cancer attributed to race are primarily associated with socioeconomic status, comorbid illnesses, molecular genetic alterations, and other disease-related characteristics identified as poor prognostic factors. One hundred fifty-two surgically staged patients with endometrial cancer (37 African-American and 115 European-American women) treated from 1990 to 1994 were analyzed for differences in demographics, disease-related characteristics, and survival. Survival was poorer for African-American women than for European-American women. African-American women had lower socioeconomic status and a higher prevalence of poor prognostic factors. Surgical stage, positive peritoneal cytology, angiolymphatic invasion, cervical stromal involvement, and a history of other malignancies were similar between the two groups. The most important predictors of survival were age at diagnosis, surgical stage, myometrial invasion, positive peritoneal cytology, cervical stromal involvement, tumor grade, aneuploidy, histology, S-phase fraction, number of poor prognostic factors, and race. Racial differences in survival were not explained by socioeconomic status, comorbid illnesses, or estrogen use. When incorporating the number of poor prognostic factors in a survival model with race and surgical stage, race ceased to be of significant prognostic value. In an analysis restricted to women with poor prognostic factors, this phenomena also occurred after adjusting for the number of poor prognostic factors. These findings suggest that the cumulative number of poor prognostic factors, not race, is a more important predictor of survival in endometrial cancer.

Aged↗
PubMed1996

Apoptotic activity of REAPER is distinct from signaling by the tumor necrosis factor receptor 1 death domain.

REAPER (RPR) is a 65-amino acid protein that is critical activator of programmed cell death in Drosophila. On the basis of sequence alignment data, it was recently proposed that RPR might represent an ancestral molecule from which the death domain in a number of proteins may have evolved. We tested this idea by examining the activity of mutations in RPR that parallel inactivation mutations of the tumor necrosis factor receptor 1 death domain. The RPR mutants retained potent apoptotic function, suggesting that cell death activity mediated by RPR is distinct from signaling by the tumor necrosis factor receptor 1 death domain.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Beneficial actions of nitrates in cardiovascular disease.

Nitroglycerin and the long-acting nitrates have been used in cardiovascular medicine for >100 years. Nitrates are widely utilized for the various anginal syndromes and are also used in congestive heart failure and patients with left ventricular dysfunction. The potential mechanisms for relief of myocardial ischemia with nitrates are multiple. The nitrovasodilators are a related group of drugs that result in the formation of nitric oxide (NO) within vascular smooth muscle cells. NO stimulates the enzyme guanylate cyclase, which results in increases in cyclic guanosine monophosphate and vasodilation. In the presence of atherosclerosis, endothelial dysfunction is ubiquitous and associated with decreased NO availability, probably due to increased destruction of NO by free radical anions. Nitrovasodilators, including the nitrates, supply exogenous NO to the vascular wall and improve the vasodilator state. When nitrates are administered, endothelial-dependent stimuli cause relaxation rather than constriction in the setting of endothelial dysfunction. Nitrates also have antiplatelet effects, and recent evidence confirms that these drugs decrease platelet aggregation and thrombosis formation. This may play an important role in the therapy of acute unstable myocardial ischemia, including unstable angina and myocardial infarction. Nitrate hemodynamic effects have been long known. They are primarily modulated through a decrease in myocardial work that results from smaller cardiac chambers operating with lower systolic and diastolic pressures. These changes are caused by a redistribution of the circulating blood volume away from the heart to the venous capacitance system, with a fall in venous return to the heart. The afterload or arterial effects of nitrates are also useful in decreasing myocardial oxygen consumption. Considerable evidence confirms a variety of mechanisms whereby nitrates increase coronary blood flow, including epicardial coronary artery dilation, stenosis enlargement, enhanced collateral size and flow, improvement of endothelial dysfunction, and prevention or reversal of coronary artery vasoconstriction. These effects help increase nutrient coronary blood flow to zones of myocardial ischemia. Recent data with the nitroglycerin patch confirm that myocardial ischemia is decreased after nitrate administration. Nitroprusside, another nitrovasodilator, is a commonly used intravenous agent for lowering arterial pressure and left ventricular filling pressure. This drug is highly effective for the treatment of acute or severe hypertension and congestive heart failure. However, there are data suggesting that nitroprusside may be deleterious in the presence of acute myocardial ischemia, perhaps by shunting blood away from zones of jeopardized myocardial blood flow. Therefore, nitroprusside cannot be recommended to treat myocardial ischemia; intravenous nitroglycerin should be used in this context.

Cardiovascular Diseases↗
PubMed1996

Dose Intensity of Chemotherapy for Childhood Cancers.

Since the formulation of the "dose-intensity" concept of anticancer therapy in the mid-1980s, the concept that "more is better" has gained general acceptance among pediatric oncologists. However, recently published clinical trials results for adults with breast cancer, germ-cell tumors, and ovarian cancer raise questions about the value of dose intensification in improving outcome. Given the differences in sensitivity between pediatric and adult tumors to cytotoxic agents, the results from these adult trials suggest a need for caution but do not suggest that evaluations of dose intensity for pediatric tumors are unwarranted (especially for a tumor such as Ewing's sarcoma, which is especially sensitive to alkylating agents). Since dose-intensive therapies have significant short- and long-term costs for the patient, it is important to obtain reliable data concerning possible benefits of this strategy. Toward this end, NCI-sponsored randomized clinical trials evaluating the role of dose intensification have been initiated for several tumors of children (including neuroblastoma, germ-cell tumors, Ewing's sarcoma, and brain tumors in infants). These trials should be completed and reported in the next two to three years, and they may make unique contributions in defining the benefits and limitations of dose intensity as a cancer treatment strategy. In the long term, however, the utility of dose intensification is limited for children with cancer because of the inherent toxicities associated with its application. Identification of agents that more specifically target tumor cells is essential. Fortunately, pediatric tumor cells do have unique biological characteristics that may be susceptible to targeting for therapeutic benefit.

Journal Article↗
PubMed1996

Therapy of angina pectoris with long-acting nitrates: which agent and when?

Nitroglycerin and the long-acting nitrates are effective antianginal agents that have been used in clinical medicine for over 100 years. These drugs are reliable, safe, familiar to clinicians, inexpensive, and easy to use. Side effects are limited to headache and postural hypotensive symptoms. Nitrate tolerance or attenuation, -ie, loss of, or decrease in, nitrate efficacy with repeated dosing-is common and represents the major drawback to chronic therapy. Carefully designed dosing regimens and/or appropriate use of nitrate formulations (to include a nitrate-free period each day) will decrease or eliminate the problem of nitrate tolerance. In head-on comparative studies, nitrates appear to be as effective as beta-blockers or calcium channel blockers in the monotherapy of chronic angina. Ideal patient characteristics for nitrate therapy include: predictably favourable response of chest pain to sublingual nitroglycerin; angina episodes suggestive of coronary vaso-constriction or spasm; left ventricular systolic dysfunction; symptoms of congestive heart failure (systolic or diastolic dysfunction).

Angina Pectoris↗
PubMed1996

Testicular touch preparation cytology.

PURPOSE: The applications, technique and limitations of testicular touch preparation cytology in evaluation of the infertile man are described. MATERIALS AND METHODS: The technique and histological results of testicular touch preparation cytology for normal specimens and various pathological conditions of male infertility are described in detail. RESULTS: Testicular touch preparation cytology is able to differentiate between late spermatids and mature spermatozoa, as well as to identify other spermatogenic elements. CONCLUSIONS: Touch preparation cytology has 2 important purposes: 1) distinguishing between maturation arrest at the late spermatid stage and normal spermatogenesis, and 2) determining whether obstruction is the cause of azoospermia. While testis biopsy is the gold standard, touch preparation cytology is an extremely important adjunct because of its ability to define whole sperm. The urologist and pathologist are better able to make a diagnosis when routine biopsy and touch preparation cytology are performed.

Cytological Techniques↗
PubMed1995

Capillary zone electrophoretic resolution of recombinant human bone morphogenetic protein 2 glycoforms. An investigation into the separation mechanisms for an exquisite separation.

Recombinant human bone morphogenetic protein 2 (rhBMP-2) is a disulfide-linked homodimeric glycoprotein (M(r) = 30,000) which induces bone formation in vivo in several animal model systems. In this paper, we report the separation of a homogeneous rhBMP-2 sample into nine peaks by capillary zone electrophoresis (CZE), using a simple, pH 2.5, phosphate buffer containing no additives. The nine peaks have been identified to be glycoforms of rhBMP-2 [designated as (rhBMP-2)2-(GlcNAc)4(ManZ), where Z varies from 10 to 18]. The difference between any adjacent pair of peaks is only one mannose residue (M(r) = 162). The ability of CZE to resolve rhBMP-2 glycoforms having the same charge and differing only 0.5% in molecular mass, without resorting to chemical complexation, is both unexpected and intriguing. Possible mechanisms explaining how the additional mannose can affect the mobility of rhBMP-2 glycoforms were explored. Zeta potentials of various glycoforms were calculated from their mobilities and interpreted in light of diffuse double layer parameters. Our results suggest that CZE employing a low-pH buffer, where proteins are highly charged, may be uniquely suitable for complex protein glycoform analysis.

Amino Acid Sequence↗
PubMed1995

The role of nitrates in coronary heart disease.

The organic nitrates are a safe and effective choice for the management of ischemic syndromes related to coronary heart disease. Although the anti-ischemic effects of these compounds have been recognized for more than a century, the mechanisms by which they exert their beneficial effects are still being delineated. In addition to their well-established venodilative activity, nitrates are now known to cause vasorelaxation of coronary arteries, coronary stenoses, and coronary collateral vessels and to prevent episodic coronary constriction. An antiplatelet effect has also been hypothesized. The three nitrate compounds currently available in the United States--nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate--are provided in a variety of dosage forms, including sublingual, transmucosal, oral, and transdermal preparations. The rapid- but short-acting nitrate preparations are useful in arresting and preventing acute attacks of angina pectoris, whereas longer-acting oral and transdermal formulations are indicated for the relief of chronic symptomatic and asymptomatic ischemia. The intermittent nitrate dosing regimens introduced in recent years have reduced the likelihood of tolerance, which greatly limited the usefulness of long-acting nitrates in the past. Intravenous infusion of nitroglycerin is particularly appropriate for the management of unstable angina and the early complications of acute myocardial infarction. Preliminary evidence suggests that intravenous nitroglycerin may also be beneficial in preventing postinfarction ventricular remodeling, although it cannot yet be recommended for this purpose.

Angina Pectoris↗
PubMed1995

Delayed omega-3 fatty acid supplements in renal transplantation. A double-blind, placebo-controlled study.

An earlier reported trial suggests that omega-3 fatty acids in fish oil supplements at 6 g/day with administration commencing at the time of engraftment may reduce acute CsA renal dysfunction. When started at the time of renal transplant, there are improvements in renal hemodynamics and blood pressure, and a decrease in rejection episodes. To examine the effect of later introduction of omega-3 fatty acids, 133 cadaver renal transplant recipients received CsA, prednisone, and AZA for 16 weeks (period 1). If patients were stable without rejection or infection activity, they were randomized to 9 g of eicosapentanoic acid (EPA), 18 g of EPA, 9 g of corn oil, or 18 g of corn oil in 1-g capsules as supplements. Glomerular filtration rate, renal blood flow, number of rejection episodes, blood pressure, and episodes of CsA nephrotoxicity were followed for 26 weeks in a double-blind manner (period 2). Ninety patients were evaluable and completed the protocol. There were 50 corn oil placebo patients, 22 low dose EPA patients, and 18 high dose EPA patients. In period 1, there were 27 rejection episodes in 21 patients without differences among subsequent treatment groups. In period 2, there were 13 rejection episodes in 4 patients. No patient with an EPA level in plasma statistically higher than placebo had a rejection episode. All allografts functioned for the entire 6 months with none lost to rejection. All 5 episodes of acute CsA nephrotoxicity occurred in placebo-treated patients without differences in whole blood CsA among toxic patients, other placebo patients, and EPA-treated recipients. At the end of the study, there were no differences in glomerular filtration rate, renal blood flow, or creatinine clearance among groups. Diastolic blood pressure fell by 9 mmHg during period 2 in high dose fish oil recipients and by 10 mmHg in low dose fish oil recipients (P < 0.05), while it rose by 2 mmHg in placebo patients. No serious adverse effects of EPA supplements were noted, although compliance based on plasma EPA was erratic. Based on our experience and that in the literature, administration of omega-3 fatty acids for purposes of kidney protection would seem to be most useful when started early after surgery. Late administration in our study was associated with minor clinical benefits.

Blood Pressure↗
PubMed1995

Chagas disease in pregnancy.

BACKGROUND: Chagas disease is a tropical disease now making its appearance in the United States as more immigration from Latin America occurs. Pregnant women with chronic infection with Trypanosoma cruzi may present with cardiac or gastrointestinal symptoms and transmit the infection to their fetuses. CASE: A 32-year-old Mexican woman presented with cardiac symptoms at 16 weeks' gestation. She was found to have a left anterior hemiblock on her electrocardiogram. Her indirect immunofluorescent antibody titer for T cruzi was positive at greater than 1:2048. Subsequently, she had a normal pregnancy and delivery. The infant's T cruzi immunofluorescent antibody titer was 1:256 at birth and had not declined at his 6-week follow-up. CONCLUSION: Obstetric care providers in the United States need to be familiar with American trypanosomiasis because it may present during pregnancy. Serious maternal disease is possible, and perinatal transmission may be seen in 2-10% of cases.

Adult↗