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B Kaplan

Publications and source records attributed to B Kaplan.

At least 163 records · Page 9Linked to original sources
PubMed1999

pH-dependent fibrillogenesis of a VkappaIII Bence Jones protein.

Disorders of immunoglobulin (Ig) synthesis that occur in malignant plasma-cell proliferation may result in either granular (LCDD) or fibrillar (AL) tissue deposition of light-chain monoclonal components. The structural features that govern the transition from soluble polypeptides to either fibrillar or granular conformational states remain undefined. Among the many factors presumed to play a role in these transitions the net charge of the molecule has been associated with folding conformation changes. The majority of the proteins involved in AL amyloidosis show acidic isoelectric points (pI 3.8-5.2), whereas most L chains with basic pIs deposit in granular patterns. In our studies a 12 kD VkappaIII fragment was purified as the main component of the fibrils isolated from myocardium and adipose tissue of the pericardium obtained post-mortem from an individual with systemic AL amyloidosis. An apparently identical 12 kD VL fragment with the same N-terminal sequence constituted the BJ protein present in the urine. This urinary protein exhibited strikingly cathodic electrophoretic mobility on agarose gels and lacked retention by anionic exchange chromatography matrices, indicative of a highly basic pI (>10). When it was subjected to in vitro fibril-formation experiments, the BJ protein adopted a fibrillar conformation only at acidic pHs, remaining aggregated but not fibrillar at physiological pH. The data indicate that a specific tissue deposition pattern involves not only structural properties of the protein but rather more complex mechanisms in which acidic micro-environments may contribute to the stabilization of amyloidogenic conformations.

Aged↗
PubMed1999

A tobacco plasma membrane calmodulin-binding transporter confers Ni2+ tolerance and Pb2+ hypersensitivity in transgenic plants.

All organisms require a minimal amount of metal ions to sustain their metabolism, growth and development. At the same time, their intrinsic metal-uptake systems render them vulnerable to toxic levels of metals in the biosphere. Using radiolabeled recombinant calmodulin as a probe to screen a tobacco cDNA library, we have discovered a protein designated NtCBP4 (Nicotiana tabacum calmodulin-binding protein) that can modulate plant tolerance to heavy metals. Structurally, NtCBP4 is similar to vertebrate and invertebrate K+ and to non-selective cation channels, as well as to recently reported proteins from barley and Arabidopsis. Here we report on the subcellular localization of NtCBP4 and the phenotype of transgenic plants overexpressing this protein. The localization of NtCBP4 in the plasma membrane was manifested by fractionating tobacco membranes on sucrose gradients or by aqueous two-phase partitioning, and subsequently using immunodetection. Several independent transgenic lines expressing NtCBP4 had higher than normal levels of NtCBP4. These transgenic lines were indistinguishable from wild type under normal growth conditions. However, they exhibited improved tolerance to Ni2+ and hypersensitivity to Pb2+, which are associated with reduced Ni2+ accumulation and enhanced Pb2+ accumulation, respectively. To our knowledge this is the first report of a plant protein that modulates plant tolerance or accumulation of Pb2+. We propose that NtCBP4 is involved in metal uptake across the plant plasma membrane. This gene may prove useful for implementing selective ion tolerance in crops and improving phytoremediation strategies.

Amino Acid Sequence↗
PubMed1999

Evaluation of urea kinetics utilizing stable isotope urea and pharmacokinetic modeling.

The determination of urea kinetics plays a central role in clinical dialysis prescription. There persist, however, significant limitations to current approaches, particularly as they pertain to rigorous explorations of urea metabolism, distribution, and removal. This report describes methodologies designed to address these limitations by coupling a stable nitrogen isotope method with strict compartmental pharmacokinetic modeling. The findings of the present study can be summarized as follows. First, the use of stable isotope labeled exogenous urea is a reliable clinically applicable method for determination of urea kinetics. Second, this method offers significant advantages in that it allows for an accurate measurement of urea distribution space, endogenous urea production, and non-renal clearance of urea. Third, this method is significantly more rigorous than urea kinetic models that utilize only endogenous urea and do not carefully fit data points. Finally, pharmacokinetic modeling suggests that a two-compartment model satisfies all aspects of urea distribution and removal, but these compartments should not be equated with specific physiologic spaces. The combination of stable isotope urea compartmental modeling is a rigorous methodology for the assessment and validation of urea kinetics.

Adult↗
PubMed1999

Increased rate of small-for-gestational-age neonates in pre-eclamptic women with preterm deliveries.

We sought to determine whether hypertensive pregnancies can be considered a distinct subgroup of premature births. All women in our centre who had had singleton preterm spontaneous deliveries over an 8-year period were divided into hypertensive and normotensive groups and compared for maternal characteristics and neonatal outcome. Of the 4175 eligible women, 9.8% (n = 410) had pre-eclampsia. These patients had higher rates of small-for-gestational-age neonates (19%, 78/410), abruptio placenta (7.8%, 32/410) and caesarean section rate (52.7%, 216/410) than the normotensive women (4.3%, 158/3765; 4.6%, 172/3765; and 19.6%, 739/3765, P < 0.001, respectively. The rate of preterm premature rupture of membranes was significantly lower in the hypertensive than in the normotensive group (5.9% vs. 17%, respectively; P < 0.001). We concluded that hypertensive women who deliver prematurely belong to a subgroup with particular characteristics. The increased rate of small-for-gestational-age neonates in pre-eclamptic women suggests that reduced uteroplacental perfusion may cause fetal growth impairment before the onset of the hypertensive disorder.

Journal Article↗
PubMed1999

Prepregnancy testing for single-gene disorders by polar body analysis.

Preventive measures for single-gene disorders are currently based on carrier screening in pregnancy and prenatal diagnosis. Although this has been extremely effective for preventing new cases of common inherited conditions, the major limitation is still termination of 25% of wanted pregnancies following detection of affected fetuses. To overcome this important problem, we developed a method for prepregnancy genetic testing that involves DNA analysis of the first and second polar bodies, which are extruded during maturation and fertilization of oocytes. We offered this option to 28 couples at risk for having children with single-gene disorders. Fifty clinical cycles were performed from these patients for the following conditions: 20 for cystic fibrosis, 18 for thalassemia, 6 for sickle cell disease, 2 each for Gaucher disease and LCHAD (long-chain 3-hydroxyacyl-COA dehydrogenase deficiency), and 1 each for hemophilia B and phenylketonuria. Oocytes obtained from these patients using in vitro fertilization procedures (IVF) were tested by a sequential multiplex nested PCR analysis of the first and second polar body to detect the gene involved simultaneously with linked polymorphic markers. A total of 191 of 399 oocytes with predicted genotype were mutation free and preselected for fertilization and transfer. In all but three cycles, one to three unaffected embryos with predicted unaffected genotypes were transferred, resulting in 20 pregnancies, from which 19 healthy children have been born. The follow-up analysis of embryos resulting from oocytes with predicted affected genotype, confirmed the diagnosis in 97% of cases, demonstrating the reliability of prepregnancy diagnosis of single-gene defects by polar body analysis.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1999

Immunochemical microanalysis of amyloid proteins in fine-needle aspirates of abdominal fat.

Diagnosis of systemic amyloidosis by fine-needle aspiration biopsy of abdominal fat is well established. A complete diagnosis now must include determination of the chemical type of amyloid. Microextracts of amyloid proteins from 11 Congo red-positive aspirate samples were analyzed with immunochemical methods. There was correspondence of the results obtained by immunohistologic and Western blotting analyses in 3 of 4 specimens with kappa light chain amyloid, 5 of 6 with lambda amyloid, and 1 with amyloid A. The method provides rapid and reliable diagnostic information necessary for classification of the chemical type of amyloid required for initiation of specific modes of therapy, with little discomfort to the patient.

Abdomen↗
PubMed1999

Microalbuminuria after pregnancy complicated by pre-eclampsia.

BACKGROUND: Microalbuminuria is an important risk factor for underlying vascular disease. Its detection after pregnancy complicated by pre-eclampsia may have predictive value for the later development of chronic hypertension or renal disease. METHOD: The study group consisted of 48 women in whom pregnancy had been complicated by pre-eclampsia. Urinary albumin excretion rate, blood pressure, and renal function parameters were assessed 2-4 months and 3-5 years after the pregnancy. Results were compared with those in 44 women after normal pregnancy. RESULTS: Mean urinary albumin excretion rate was significantly higher in the study group than in the controls both at 2-4 months after delivery (27.0 +/- 33 vs 6.1 +/- 3.3 mg/24 h) and at 3-5 years after delivery (23.5 +/- 26.8 vs 6.7 +/- 2.8 mg/24 h) (P = 0.001). The rate of occurrence of microalbuminuria was not significantly different between the early (58%) and late (42%) time-points within the study group or between the nulliparous and the multiparous women. CONCLUSIONS: A history of pregnancy complicated by pre-eclampsia is associated with a high occurrence of microalbuminuria. Whether the presence of microalbuminuria reflects a possible underlying vascular disease in affected patients needs to be further investigated in large-scale studies.

Adult↗
PubMed1999

Correlation between pretransplantation test dose cyclosporine pharmacokinetic profiles and posttransplantation sirolimus blood levels in renal transplant recipients.

We sought to determine whether pretransplantation test dose pharmacokinetic measurements of cyclosporine (CsA) concentrations would forecast the posttransplantation blood concentrations of sirolimus in renal transplant patients treated de novo with CsA, sirolimus, and prednisone. All 44 renal transplant recipients enrolled in Phase I/II studies of de novo posttransplantation therapy with sirolimus, CsA, and prednisone underwent pretransplantation pharmacokinetic profiling after having received paired intravenous (i.v.) and oral test doses of CsA. After transplantation, all patients were treated with CsA on a once- or twice-daily schedule (according to a concentration-controlled regimen), with tapering doses of prednisone, and with fixed doses of sirolimus on a once-daily schedule. Patients were divided into four cohorts based on the deviation of their pretransplantation CsA clearance or bioavailability values from the mean. Patients with high pretransplantation CsA clearance rates displayed a significantly lower mean posttransplantation value of sirolimus trough concentrations than patients with low pretransplantation CsA clearance rates. In contrast, values for pretransplantation absolute oral CsA bioavailability failed to correlate with the mean posttransplantation concentration of sirolimus but did predict posttransplantation CsA bioavailability. Therefore, pretransplantation CsA clearance rate estimates may forecast posttransplantation sirolimus concentrations, possibly guiding use of sirolimus therapy to achieve an optimal ratio of concentration-dependent immunosuppressive versus toxic effects.

Biological Availability↗
PubMed1999

A limited sampling strategy for the estimation of 12-hour SangCya and neoral AUCs in renal transplant recipients.

Neoral and SangCya are new cyclosporine formulations with more consistent pharmacokinetic profiles than the older formulation of cyclosporine, Sandimmune. Limited sampling strategies have been derived to estimate the full area under the curve (AUC) for both Neoral and Sandimmune. In addition, no limited sampling strategy has been derived for SangCya, and no rigorous prospective testing has been done on any of these formulas. The authors studied 32 renal transplant patients who received Neoral and then SangCya during a formulation conversion study. Full AUCs were drawn on all patients (twice while on Neoral, once while on SangCya). Abbreviated formulas were derived using linear regression models and then tested for the prediction error. The authors found that several abbreviated formulas offer excellent estimations of the full AUC for both SangCya and Neoral. The generated formulas worked equally well with either formulation. In addition, the authors found that limited sampling strategies using a 1.5-hour sample may predict a full AUC more accurately than those that use a 2-hour sample. The use of these abbreviated formulas allows for a convenient and accurate estimate of CsA exposure.

Area Under Curve↗
PubMed1999

The effect of renal insufficiency on mycophenolic acid protein binding.

Mycophenolate mofetil (MMF) is commonly used in solid organ transplant recipients. MMF is converted to mycophenolic acid (MPA) upon reaching the systemic circulation. Many acidic drugs have altered protein binding in renal failure, and it is possible that MPA protein binding may be decreased. The authors studied 23 renal transplant recipients: 8 transplant patients (7 kidney, 1 kidney/pancreas) with chronic renal insufficiency (CRI) and 15 renal transplant patients with preserved renal function. Plasma was obtained for kinetic profiles of total MPA, free MPA, and its glucuronide metabolite (MPAG). Plasma was obtained from 10 hemodialysis patients and 8 healthy control volunteers to assess in vitro differences in MPA protein binding. Average free fraction of MPA in patients with chronic renal insufficiency was more than double that of patients with normal renal function (5.8 +/- 2.7 vs. 2.5 +/- 0.4, p < 0.01). Free MPAAUC was almost doubled in the patients with chronic renal insufficiency versus controls (2.04 +/- .08 vs. 1.03 +/- 0.6, p < 0.01). MPA protein binding is decreased, and free MPA concentrations are increased in patients with chronic renal failure.

Abdominal Pain↗
PubMed1999

Does female age affect embryo morphology?

Deteriorating oocyte quality is commonly believed to be the primary determinant of the decreased implantation potential in older women. We assessed the influence of age on embryo morphology in standard in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) modalities. All 6350 consecutive embryos (2990 IVF, 3360 ICSI) obtained in our Assisted Reproductive Technology Unit from January 1996 through June 1997 were included. High quality embryos were defined as those with equal-sized blastomeres and < 10% fragmentations and a cleavage rate of four cells on day 2 or eight cells on day 3 transfers. The results were analyzed for the standard IVF group, the ICSI group, and the ICSI subgroup with severe male factor infertility (< or = 1 x 10(6) total motile spermatozoa in the ejaculate). For standard IVF, a positive association was observed between female age and increased proportion of good quality embryos. No such association was detected for the ICSI cycles (whole group or subgroup). We conclude that in standard IVF, embryo quality, as reflected by embryo morphology, does not deteriorate with increased maternal age.

Adult↗
PubMed1999

Quality of cryopreserved testicular sperm in patients with obstructive and nonobstructive azoospermia.

PURPOSE: Sperm retrieved by testicular sperm extraction is routinely used to attempt pregnancy by in vitro fertilization-intracytoplasmic sperm injection. We evaluated the efficacy of cryopreserving testicular sperm collected by testicular sperm extraction at diagnostic biopsy. MATERIALS AND METHODS: A total of 73 men with obstructive and 42 with nonobstructive azoospermia underwent testicular sperm extraction at diagnostic biopsy. Sperm was retrieved and cryopreserved in all cases of obstruction and in 15 of nonobstructive azoospermia cases. Before freezing we determined sperm count, motility, morphology and viability, and after thawing we assessed sperm motility and viability. In 17 couples a total of 20 cycles of in vitro fertilization-intracytoplasmic sperm injection were performed and fertilization, cleavage and pregnancy rates were determined in cases of obstruction and nonobstruction. RESULTS: Sperm count and morphology were lower in the testicular biopsies of men with nonobstructive versus obstructive azoospermia. Motility was low or absent in all testicular sperm extraction specimens. Importantly, pre-freeze (63%) and post-thaw (31%) viability was the same in both patient groups. After in vitro fertilization-intracytoplasmic sperm injection using frozen and thawed testicular sperm the fertilization, cleavage, implantation and clinical pregnancy rates were 60, 86, 16 and 50%, respectively. Using cryopreserved sperm we observed no differences in outcome of any in vitro fertilization-intracytoplasmic sperm injection procedure in patients with obstructive versus nonobstructive azoospermia. CONCLUSIONS: Cryopreservation of testicular sperm provides enough good quality sperm after thawing to result in excellent in vitro fertilization-intracytoplasmic sperm injection outcomes. Cryopreservation does not adversely affect intracytoplasmic sperm injection outcomes, including pregnancy rate. Therefore, we recommend routine testicular sperm extraction and cryopreservation of sperm at testicular biopsy.

Cryopreservation↗
PubMed1999

Pelvic abnormalities in hysterectomized patients-role of early postoperative ultrasonographic evaluation.

OBJECTIVE: To assess the incidence of post-hysterectomy pelvic fluid collection in the early postoperative period and to study its natural history. STUDY DESIGN: Cross-sectional, prospective, observational study. PATIENTS AND METHODS: The study sample comprised 36 consecutive patients undergoing hysterectomy for benign conditions in our department. All patients underwent two pelvic ultrasonographic examinations, the first on the third postoperative day and the second one year later. All postoperative complications were thoroughly evaluated. RESULTS: Thirty-two patients completed the study evaluations. Abnormal ultrasonographic findings were detected in 4 of them on the early postoperative scan. Three (9.4% of the sample) had pelvic fluid collections which persisted on the follow-up scan. The fourth patient had a simple ovarian cyst 4 cm in diameter which disappeared on follow-up. None of the patients with pelvic fluid collections had a febrile morbidity during the postoperative course. CONCLUSIONS: Transvaginal ultrasonography can detect asymptomatic early postoperative pelvic fluid collections and enables conservative management, thereby reducing patients stress, medical costs, and the need for unnecessary interventions.

Ascitic Fluid↗
PubMed1999

The role of intravenous albumin in the prevention of severe ovarian hyperstimulation syndrome. A pilot experimental study.

OBJECTIVE: To evaluate the role of intravenous albumin in the prevention of severe ovarian hyperstimulation syndrome (OHSS). DESIGN: A pilot experimental study. MATERIAL AND METHODS: Ovarian hyperstimulation was induced in 5 rabbits using human menopausal gonadotropin/human chorionic gonadotropin, after pretreatment without (control group) or with bovine serum albumin (BSA group). RESULTS: Despite an increase in serum protein levels, the BSA group showed comparable delta increase in body weight and degree of ascites formation. CONCLUSIONS: Intravenous albumin did not prevent severe OHSS in a rabbit model despite the observed increase in serum oncotic pressure.

Animals↗
PubMed1999

Ethnographic interviews to elicit patients' reactions to an intelligent interactive telephone health behavior advisor system.

Information technology is being used to collect data directly from patients and to provide educational information to them. Concern over patient reactions to this use of information technology is especially important in light of the debate over whether computers dehumanize patients. This study reports reactions that patient users expressed in ethnographic interviews about using a computer-based telecommunications system. The interviews were conducted as part of a larger evaluation of Telephone-Linked Care (TLC)-HealthCall, an intelligent interactive telephone advisor, that advised individuals about how to improve their health through changes in diet or exercise. Interview findings suggest that people formed personal relationships with the TLC system. These relationships ranged from feeling guilty about their diet or exercise behavior to feeling love for the voice. The findings raise system design and user interface issues as well as research and ethical questions.

Anthropology, Cultural↗
PubMed1999

Red blood cell zinc protoporphyrin measurement for assessment of peripartum iron deficiency.

OBJECTIVE: To study the effectiveness of the rapid red blood cell zinc protorphyrin (RBC-ZPP) test for the detection of women with iron-deficiency anemia in the peripartum period. DESIGN: Blood was drawn prospectively from 150 healthy parturient women upon admission to the labor and delivery room and 72 hours after delivery. Concentration of RBC-ZPP was measured and correlated with hemoglobin level (p = 0.001), mean corpuscular volume (p = 0.002), hematocrit (p = 0.0001), platelet count (p = 0.002), and serum iron (p = 0.0001), serum ferritin (p = 0.0001) and serum transferrin (p = 0.0001) concentrations. RESULTS: RBC-ZPP concentration showed a significant increase from pre-delivery to 72 hours post-delivery. This change correlated significantly with the changes in all the other parameters studied. CONCLUSION: The RBC-ZPP test is a reliable, rapid, easy-to-perform, and inexpensive method of screening low-risk women, after uneventful vaginal delivery, for iron deficiency.

Anemia, Iron-Deficiency↗
PubMed1999

Renal transplantation at the University of Michigan 1964 to 1999.

The Michigan Kidney Transplant Program has existed for 35 years. Outcomes have improved dramatically as the one-year survival of cadaver kidney grafts increased from 25% to 85-90%. Patient deaths in the first year are now uncommon. Indications for renal transplantation have been extended to infants, the elderly, diabetics and to patients with other significant health problems who would not have been candidates in the past. Chronic administration of large doses of corticosteroids is no longer necessary and the associated morbidity is largely avoided. Improvements in immunosuppression, especially the introduction of cyclosporine, account for much of this progress. With success has come increasing demand. Unfortunately, the gap between the number of available donor kidneys and the number of patients listed for a cadaver transplant continues to increase rather than diminish. Greater acceptance of volunteer donation, as has occurred in our own program, will help to reduce this shortage. If the past forecasts the future, we can anticipate extraordinary advances during the next 35 years.

Actuarial Analysis↗