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Biomedical subjects

M Kaplan

Publications and source records attributed to M Kaplan.

At least 127 records · Page 7Linked to original sources
PubMed1996

Postural orientation modifications in autism in response to ambient lenses.

Autistic children often display abnormal postures, head tilts, and other spatial management dysfunctions. Methods were introduced to measure spatial orientation in tasks in a group of fourteen autistic children in Montreal, Canada. Ambient lenses were found to improve posture, correct head tilts, and improve ball catching abilities. A model of spatial orientation is described and recommendations are made to incorporate ambient lenses in treatment programs.

Adolescent↗
PubMed1996

Development and application of HHV-6 antigen capture assay for the detection of HHV-6 infections.

An HHV-6 antigen capture assay measuring gp116/64/54 antigen was developed. This ELISA is specific for HHV-6 Variants A and B, does not cross react with other human herpesviruses, is sensitive, stable, quantitative, and can detect antigen in body fluids and cell cultures. Relative to virus isolation or techniques for measuring HHV-6 nucleic acids, the assay is much simpler and less expensive to perform. Plasmas/sera (413) obtained from healthy donors, children with Exanthem subitum, febrile illnesses, patients with Chronic Fatigue Syndrome, and AIDS patients tested by antigen capture assay demonstrated that the assay is useful in clinical laboratory settings. The capture assay can also be used to monitor cell cultures for virus isolation, production, quantitation, and antiviral agent screening.

AIDS-Related Opportunistic Infections↗
PubMed1996

Pathological crying and laughing: treatment with sertraline.

OBJECTIVE: To evaluate the efficacy of sertraline for treating pathological laughing and crying after stroke. DESIGN: Case series. SETTING: Inpatient rehabilitation units of a community and a tertiary-care hospital. PATIENTS: One patient was a 62-year-old right-handed man who had two strokes approximately 2 years apart and had computed tomography consistent with a cerebral infarct involving the left middle cerebral artery branches in the left parietal lobe. A second patient was a 72-year-old right-handed man who had a right middle cerebral artery infarct. He had a questionable history of depression prior to the stroke. INTERVENTION: Both patients had poststroke labile affect that was interfering with their rehabilitation. Sertraline was prescribed. MAIN OUTCOME MEASURES: Pretreatment and posttreatment scores on the Pathological Crying and Laughing Scale and Functional Independent Measure. RESULTS: Both patients showed significant improvement after taking sertraline-improvement that was reflected in their pretreatment and posttreatment scores on the Pathological Crying and Laughing Scale and Functional Independent Measure. The staff noted improvements in sleeping, eating, social interaction, and therapy participation. Both patients tolerated the sertraline well and had no significant side effects.

1-Naphthylamine↗
PubMed1996

Conjugated bilirubin in neonates with glucose-6-phosphate dehydrogenase deficiency.

We used a system capable of measuring conjugated bilirubin and its monoconjugated and diconjugated fractions in serum to assess bilirubin conjugation in 29 glucose-6-phosphate dehydrogenase (G6PD)-deficient, term, male newborn infants and 35 control subjects; all had serum bilirubin levels > or = 256 mumol/L (15 mg/dI). The median value for diconjugated bilirubin was lower in the G6PD-deficient neonates than in control subjects (0.06 (range 0.00 to 1.84) vs 0.21 (range 0.00 to 1.02) mumol/L, p = 0.006). Diglucuronide was undetectable in 11 (38.9%) of the G6PD-deficient infants versus 3 (8.6%) of the control subjects (p = 0.015). These findings imply a partial defect of bilirubin conjugation not previously demonstrated in G6PD-deficient newborn infants.

Bilirubin↗
PubMed1996

The electroneutral Na(+)-(K+)-Cl- cotransport family.

Recently the molecular identification of the major electroneutral sodium-potassium-chloride entry mechanisms present on apical membranes of distal nephron segments of the mammalian kidney, on basolateral membranes of many non-renal epithelial cells and on certain non-epithelial tissues has been achieved. These transporters represent a major pathway for cellular uptake of chloride critical for chloride absorptive and secretory processes and for cell volume regulation following cell shrinkage. In the mammalian kidney, these sodium-coupled chloride cotransporters represent the major target sites for clinically useful diuretics including the "loop" diuretics [furosemide (Lasix) and bumetanide (Bumex)] and thiazides (such as, chlorothiazide, hydrochlorothiazide and metolazone). Although these Na-(K)-Cl cotransporters exhibit functional and pharmacological differences, they clearly evolved from a common ancestral gene and thus form a new gene family. This information is already advancing our understanding of the evolution, structure and function of these transporters both in renal handling of sodium and in hypertension.

Animals↗
PubMed1996

Contribution of haemolysis to jaundice in Sephardic Jewish glucose-6-phosphate dehydrogenase deficient neonates.

We determined the contribution of haemolysis to the development of hyperbilirubinaemia in glucose-6-phosphate dehydrogenase (G-6-PD) deficient neonates and G-6-PD normal controls. Blood carboxyhaemoglobin (COHb), sampled on the third day of life, was measured by gas chromatography, corrected for inhaled carbon monoxide (COHbC), and expressed as a percentage of total haemoglobin concentration (Hb). Serum bilirubin was tested as clinically necessary. 37 non-jaundiced (peak serum total bilirubin (PSTB) < or = 255 mumol/l) and 20 jaundiced (PSTB > or = 257 mumol/l) G-6-PD-deficient neonates were compared to 31 non-jaundiced and 24 jaundiced controls with comparable PSTB values, respectively. COHbC values for the entire G-6-PD deficient group were higher than in the controls (0.75 +/- 0.17% v 0.62 +/- 0.19%, P < 0.001). COHbC and PSTB values did not correlate in the G-6-PD-deficient group (r = 0.15, P > 0.05) but did in the controls (r = 0.58, P < 0.001). COHbC values were increased to a similar extent in the G-6-PD-deficient, non-jaundiced (0.72 +/- 0.16%), the G-6-PD-deficient, jaundiced (0.80 +/- 0.19%) and the control, jaundiced (0.75 +/- 0.18%) subgroups, compared to the control, non-jaundiced subgroup (0.53 +/- 0.13%) (P < 0.05). Although present in G-6-PD deficient neonates, increased haemolysis was not directly related to the PSTB.

Carbon Monoxide↗
PubMed1996

Induction androgen deprivation therapy before radical prostatectomy for prostate cancer--initial results.

OBJECTIVE: To determine if androgen deprivation therapy (ADT) on induction decreases the incidence of positive surgical margins and the subsequent risk of disease progression. PATIENTS AND METHODS: Between January 1992 and July 1994, 160 men with prostate cancer underwent radical retropubic prostatectomy (RP) and bilateral pelvic node dissection (PLND). Forty men (mean age 64.2 years) with either a higher clinical stage or a significant increase in serum prostate-specific antigen (PSA) level (P < 0.001) received induction ADT with a luteinizing hormone-releasing hormone (LH-RH) analogue alone (six patients), or with an anti-androgen (34 patients), 3-20 months before undergoing RP. The remaining 120 men (mean age 64 years) underwent surgery alone and served as historical controls. Prostatectomy specimens were evaluated using step-sections at 2-3 mm intervals and whole-mount reconstruction. The clinical and pathological results were compared. RESULTS: There was a clinically significant decrease in the size of the prostate in almost all patients treated with ADT. After ADT the mean PSA level declined by > 95% from the levels before RP (P < 0.001). Of 40 men receiving ADT and the 120 controls patients, nine (22.5%) and 49 (40.8%) had positive margins (P < 0.05), nine (22.5%) and 18 (15%) had seminal-vesicle invasion (P = 0.90) and one (2.5%) and two (1.6%) had lymph-node metastases (P = 0.73), respectively. At a mean 17.6 months (range 2-29), 20 of the control patients were lost to follow-up. PSA levels were elevated (> 0.4 ng/mL) in seven (17.5%) of the men who received ADT and 14 (14%) of the control patients (P = 0.60). To date, all patients are alive. CONCLUSIONS: The results of this study suggest that neoadjuvant ADT before RP is beneficial in men with a high likelihood of having a positive surgical margin. A prospective randomized trial is necessary to determine if there is a benefit in progression-free and overall survival.

Androgen Antagonists↗
PubMed1996

Intravenous immune globulin in neonatal immune hemolytic disease: does it reduce hemolysis?

We studied the effect of intravenous immune globulin (IVIG) on hemolysis in term, hyperbilirubinemic, Coomb's positive infants utilizing measurement of carboxyhemoglobin fraction corrected for inhaled carbon monoxide (COHbc), a sensitive indicator of hemolysis. COHbc values were determined before and after IVIG infusion. In those babies who responded with a decrease in serum total bilirubin (n = 19), no exchange transfusions were required and COHbc levels decreased significantly by 24 h post-IVIG from 1.37 +/- 0.31 to 1.12 +/- 0.26% tHb (p < 0.0001). There were no corresponding decreases in COHbc levels (1.989 +/- 0.54 to 1.82 +/- 0.48% tHb; p > 0.05) among those whose serum bilirubin levels did not decrease in response in to IVIG (n = 7), and all of these infants required exchange transfusions. Furthermore, the extent of the decrease in COHbc was related to the degree of decrease in serum bilirubin levels, such that the percentage decrease of bilirubin at 24 h was directly correlated with the percentage decrease of COHbc at 24 h (p = 0.007). We conclude that IVIG, when successful, inhibits hemolysis in these infants.

Erythroblastosis, Fetal↗
PubMed1996

Intravenous immune globulin in neonatal ABO isoimmunization: factors associated with clinical efficacy.

OBJECTIVE: Intravenous immune globulin (IVIG) reduces jaundice in many but not all cases of neonatal isoimmunization. We sought to elucidate the type of infant most likely to benefit from IVIG administration by attempting to define pretreatment parameters associated with both clinical symptomatology and therapeutic responsiveness to IVIG. METHODS: Term, healthy Coombs-positive infants were studied prospectively. IVIG was administered if, despite phototherapy, serum bilirubin reached > or = 222 mumol/l (13 mg/dl) at < or = 24 h of age and/or > or = 274 mumol/l (16 mg/dl) at > 24 h of age. Clinical data including serial serum total bilirubin levels, rate of bilirubin rise on day 1 of life, serial corrected carboxyhemoglobin levels (a sensitive indicator of hemolysis) and total hemoglobin (tHb) levels were collected. RESULTS: Infants were classified as IVIG responders (n = 18), those in whom total serum bilirubin levels either remained stable or decreased following IVIG administration; IVIG nonresponders (n = 5), those who developed a total serum bilirubin of > or = 2 mg/dl greater than pre-IVIG bilirubin levels within the first 24 h after IVIG administration, or nontreated, those not meeting IVIG treatment criteria (n = 13). Four of the five nonresponders proceeded to require exchange transfusion vs. none of the others (p < 0.001). Four of the five nonresponders had a pretreatment rate of bilirubin rise of > or = 1 mg/dl/h as compared with only 1 of 18 responders and none of the nontreated (p < 0.001). Pretreatment tHb levels were also different (13.2 +/- 1.3 vs. 15.5 +/- 2.3 vs. 17.7 +/- 2.4 g/dl for nonresponders vs. responders vs. nontreated infants, respectively; p < 0.005). The highest pretreatment COHbc levels were seen in the nonresponders (1.8 +/- 0.7 vs. 1.4 +/- 0.3 vs. 0.9 +/- 0.3% tHb, respectively). CONCLUSIONS: Our 3 groups represent a spectrum of hemolysis, ranging from severe to moderate to mild. This spectrum appears to relate not only to the severity of hemolysis, but also to the therapeutic responsiveness to IVIG. We speculate that some or all of the factors identified can be used prospectively to predict the subsequent clinical course of ABO-incompatible infants and to facilitate optimal management.

ABO Blood-Group System↗
PubMed1996

Angiotensin II-modified LDL is taken up by macrophages via the scavenger receptor, leading to cellular cholesterol accumulation.

The incidence of myocardial infarction is significantly higher in hypertensive patients with increased plasma concentration of angiotensin (Ang) II. Ang II was shown to bind to LDL in vitro, and in the present study we showed its binding to LDL in vivo. Ang II (10(-7) mol/L) was incubated with LDL for 3 hours at 37 degrees C, followed by reseparation of the modified lipoprotein (Ang II-LDL) and its incubation with J-774 A.1 macrophages. Binding of Ang II to LDL significantly increased the lipoprotein protein degradation (by 25%) and its cell association (by 75%) compared with nontreated LDL. Unlike Ang II-LDL, both Ang I-LDL and Ang III-LDL were taken up by macrophages similar to native LDL. The lipid composition and size of Ang II-LDL were similar to those of native LDL, and it was not aggregated. Ang II-LDL was not oxidized, as the contents of malondialdehyde and peroxides were not different from those found in native LDL. On heparin-Sepharose column chromatography, Ang II-LDL was eluted in the void volume, like acetylated LDL (Ac-LDL) and unlike native LDL, which binds to heparin. The cellular degradation of Ang II-125I-labeled LDL by J-774 A.1 macrophages of Ang II-125I-labeled LDL by J-774 A.1 macrophages was studied in the presence of a 50-fold excess of nonlabeled native LDL, Ang II-LDL, Ac-LDL, or oxidized LDL (Ox-LDL). Whereas native LDL had no effect on the degradation of Ang II-125I-LDL by the macrophages, Ac-LDL, Ox-LDL, and Ang II-LDL reduced the cellular uptake of the lipoprotein by 77%, 82%, and 87%, respectively. Similarly, fucoidin but not free Ang II reduced macrophage degradation of the labeled Ang II-LDL. We conclude that Ang II can modify LDL to a form that is not oxidized or aggregated but is still taken up at an enhanced rate by macrophages via the scavenger receptor.

Angiotensin II↗
PubMed1996

Effect of dietary supplementation of beta-carotene on human monocyte-macrophage-mediated oxidation of low density lipoprotein.

Oxidative modification of low density lipoprotein (LDL), a key step in early atherosclerosis, is protected by the lipoprotein-associated antioxidants. The present study analyzes the effect of beta-carotene in plasma, in LDL and in monocyte-macrophages, on macrophage-mediated oxidation of LDL. We investigated the effect of dietary supplementation of beta-carotene on plasma lipid peroxidation [induced by AAPH (2,2-Azobis-2-amidinopropane hydrochloride)] and on cell-free and cell-mediated oxidation of LDL by human monocyte-derived macrophages (HMDM) in the presence of CuSO4. Significant enrichment with beta-carotene was noted in plasma (twofold), in LDL (2.6-fold) and in HMDM (1.6-fold) 2 weeks after dietary supplementation with 180 mg/day of beta-carotene. Plasma lipid peroxidation analyzed by conjugated dienes generation decreased by 22% (P < 0.01) and LDL susceptibility to oxidation analyzed by malondialdehyde generation decreased by 40% (P < 0.01). After beta-carotene supplementation, beta-carotene-enrichment of HMDM capacity to oxidize native LDL, whereas beta-carotene enrichment of LDL significantly reduced LDL oxidation. In conclusion, then, our results suggest that beta-carotene content of LDL, but not that of the macrophages, is responsible for the inhibition of oxidation of LDL.

Administration, Oral↗
PubMed1995

Isolation and characterization of an immortal neoplastic cell line (KS Y-1) from AIDS-associated Kaposi's sarcoma.

BACKGROUND: Acquired immunodeficiency syndrome (AIDS) is associated with the occurrence of tumors such as Kaposi's sarcoma (KS) and B-cell lymphoma. However, no evidence exists yet that human immunodeficiency virus type 1, the causative agent of AIDS, is directly responsible for cell transformation. It is also not clear whether KS lesions, which are of complex cellularity, contain tumor cells derived from a true monoclonal malignancy (originating from a single malignant cell) or whether the lesions are just polyclonally hyperplastic in nature (containing increased numbers of normal cells). In fact, the presence of malignant KS cells has never been unequivocally shown in AIDS-associated KS, and previously isolated KS cell cultures were not immortal or malignant. PURPOSE: Our purpose was to (a) utilize technology that could facilitate isolation and enrichment of tumor cells from AIDS-associated KS lesions, (b) establish and characterize an immortalized KS cell line, and (c) test the malignant potential of such a cell line in animal models. METHODS: Mononuclear cells were isolated from 2.5 L of pleural effusion from an AIDS-associated KS patient. T-lymphocytes, B-lymphocytes, monocytes/macrophages, and fibroblasts were removed by a cytotoxicity method, using monoclonal antibodies specific for cell surface markers and baby rabbit complement. KS cells were cultured in the absence of exogenous growth factors in an effort to select for transformed cells capable of self-sustained growth. The karyotype abnormalities were detected by G-banded marker studies, and phenotypic markers were determined by indirect immunofluorescence and immunocytochemical methods. Beige nude XID and severe combined immunodeficient mice were used to evaluate the tumorigenic, angiogenic, and metastatic potentials of cells. RESULTS: An immortalized cell line, named KS Y-1, was isolated. Its phenotype is similar to that of endothelial cells with positive CD34 and CD31 markers. Tetraploid chromosomal abnormalities were found in primary fresh KS tissue and in vitro passages of KS Y-1 cells. These cells promoted tumorigenesis, angiogenesis, and metastasis in immunodeficient mice. Tumors produced at the site of injection as well as metastases in the lung, spleen, pancreas, gastrointestinal tract, and skin showed a human tetraploid karyotype. KS Y-1 cells show high plating efficiency. CONCLUSION: The KS Y-1 cell line could be the first evidence of AIDS-associated KS cells that may develop clones with an indisputable malignant cell phenotype. IMPLICATIONS: KS Y-1 cells in the in vivo mouse model can be used to study the effects of therapeutic compounds in advanced KS.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Expression of the Fas antigen in patients infected with human immunodeficiency virus.

Lymphocytes from patients with HIV infection have been shown to undergo accelerated apoptosis. Fas antigen is a cell surface protein known to initiate an apoptotic signal. Therefore, we undertook a study to examine the expression of the Fas antigen during HIV infection. Using three color flow cytometry, expression of the Fas antigen on lymphocytes of 23 HIV infected individuals (CDC category 2, CD4 200-499 cells/microL, n = 10; CDC category 3, CD4 < 200 cells/microL, n = 13) and 10 healthy controls was examined. Both CD3+CD4+ and CD3+CD8+ subsets were examined for their expression of this marker. In lymphocytes of healthy controls, 47% of the CD3+CD4+ and 45% of the CD3+CD8+ cells were Fas antigen positive. This percentage was significantly increased in CD4 cells from HIV infected patients belonging to CDC category 3, but was unchanged from normal values in CDC category 2 subjects. The increase in the percentage of CD4+ T cells expressing Fas antigen in patients correlated significantly with the decrease in circulating CD4 T cell count (P < 0.009). In addition, by examining mean fluorescence intensity, we found that the amount of Fas expression per cell was increased threefold in CD3+CD4+ cells and increased twofold in CD3+CD8+ cells in category 3 patients. These results demonstrate that an increase in Fas antigen expression occurs during HIV infection.

Adult↗
PubMed1995

Instrumentation for automated determination of protein stability.

A new instrument system has been developed that automatically carries out solvent and thermal denaturations of proteins using fluorescence as a probe of structure. This instrument also automatically performs pH titrations and can make kinetic measurements on the time scale of seconds. The design philosophy and implementation are described. The prototype instrument was subjected to extensive testing. The instrument can very reproducibly and accurately collect data that allow the calculation of the thermodynamics of protein denaturation. This data collection can proceed without human intervention after acquisition start until the data are saved.

Guanidine↗
PubMed1995

Gamma delta T cells function in cell-mediated immunity to acute blood-stage Plasmodium chabaudi adami malaria.

To determine whether gamma delta T cells are essential for the resolution of acute Plasmodium chabaudi adami (P. c. adami) malaria, we depleted gamma delta T cells from C57BL/6 mice with hamster monoclonal anti-TCR gamma delta Ab treatment. During the period in which control mice that had received normal hamster IgG completely resolved infections, gamma delta T cell-depleted mice were unable to suppress their infections. Because the number of splenic CD4+ alpha beta T cells in these anti-TCR-gamma delta-treated mice with nonresolving malaria was similar to control mice, it appears that CD4+ alpha beta T cells alone cannot mediate early resolution even though they are known to play a critical role in immunity to blood-stage malaria. Mice treated with anti-CD4 mAb also failed to resolve P. c. adami malaria. Depletion of CD4+ alpha beta T cells from the spleens of infected mice resulted in minimal expansion of the splenic CD4- gamma delta T cell subset compared with infected control mice. Together, these findings indicate that activation of the gamma delta T cell subset, which requires the presence of CD4+ alpha beta T cells, is essential for resolution of acute P. c. adami malaria. To determine whether gamma delta T cells require either Abs or B cells to achieve their protective activity, B cell-deficient JHD mice were treated with the same depleting anti-TCR-gamma delta Abs. Whereas control JHD mice injected with hamster IgG resolved acute P. c. adami malaria, JHD mice depleted of gamma delta T cells failed to do so. We conclude that gamma delta T cells suppress P. c. adami parasitemia by mechanisms of immunity independent of Ab and B cells.

Acute Disease↗
PubMed1995

Angiotensin II stimulates macrophage-mediated oxidation of low density lipoproteins.

Increased incidence of myocardial infarction was found in hypertensive patients with high plasma renin activity and increased susceptibility to oxidation was demonstrated in low density lipoprotein (LDL) that was obtained from hypertensive patients. As lipid peroxidation was demonstrated in areas of the atherosclerotic lesion, we sought to analyze the effect of angiotensin II (AN-II) on LDL oxidation, both in vitro and in vivo. Preincubation of J-774 A.1 macrophage-like cell line or mouse peritoneal macrophages (MPM) with AN-II (10(-7) M) for 1 h at 37 degrees C, followed by the addition of LDL for a further 18 h of incubation, resulted in a substantial increase in macrophage-mediated oxidation of LDL (by 55% and 19%, respectively). Similarly, incubation of LDL with MPM harvested from AN-II-injected mice resulted in a substantially increased oxidation of the lipoprotein by up to 90% in comparison to saline-injected mice. Analysis of cellular lipid peroxidation in the MPM themselves, in both the in vitro and the in vivo studies, revealed a 25% or 90% increased macrophage lipid peroxidation, respectively. The mechanism of AN-II-mediated cellular lipid peroxidation involved AN-II binding to its receptor on macrophages as saralasin, an AN-II receptor antagonist, completely inhibited this effect. Inhibitors of phospholipases A2, C and D substantially reduced macrophage lipid peroxidation, suggesting the involvement of phospholipases A2, C and D substantially reduced macrophage lipid peroxidation, suggesting the involvement of phospholipid metabolites in AN-II-mediated macrophage lipid peroxidation, suggesting the involvement of phospholipid metabolites in AN-II-mediated macrophage lipid peroxidation. Extracellular calcium ions, which active phospholipases, were also essential for AN-II-mediated macrophage lipid peroxidation since calcium channel blockers substantially inhibited cellular lipid peroxidation. Finally, the nature of the oxidant and oxygenase involved in AN-II-mediated cellular lipid peroxidation was studied using oxygenase inhibitors. Angiotensin II-mediated macrophage lipid peroxidation was found to involve the action of cellular NADPH oxidase as well as 15-lypoxygenase. We conclude that AN-II stimulates macrophage-mediated mediated oxidation of LDL secondary to cellular lipid peroxidation, and this may have a role in the accelerated atherosclerosis found in hypertensive patients.

Angiotensin II↗