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Biomedical subjects

M A Kaplan

Publications and source records attributed to M A Kaplan.

At least 37 records · Page 2Linked to original sources
PubMed1999

Selective effect of 2',6'-dihydroxy-4'-methoxychalcone isolated from Piper aduncum on Leishmania amazonensis.

2',6'-Dihydroxy-4'-methoxychalcone (DMC) was purified from the dichloromethane extract of Piper aduncum inflorescences. DMC showed significant activity in vitro against promastigotes and intracellular amastigotes of Leishmania amazonensis, with 50% effective doses of 0.5 and 24 micrograms/ml, respectively. Its inhibitory effect on amastigotes is apparently a direct effect on the parasites and is not due to activation of the nitrogen oxidative metabolism of macrophages, since the production of nitric oxide by both unstimulated and recombinant gamma interferon-stimulated macrophages was decreased rather than increased with DMC. The phagocytic activity of macrophages was functioning normally even with DMC concentrations as high as 80 micrograms/ml, as seen by electron microscopy and by the uptake of fluorescein isothiocyanate-labeled beads. Ultrastructural studies also showed that in the presence of DMC the mitochondria of promastigotes were enlarged and disorganized. Despite destruction of intracellular amastigotes, no disarrangement of macrophage organelles were observed, even at 80 micrograms of DMC/ml. These observations suggest that DMC is selectively toxic to the parasites. Its simple structure may well enable it to serve as a new lead compound for the synthesis of novel antileishmanial drugs.

Animals↗
PubMed1999

Improvement of in vitro and in vivo antileishmanial activities of 2', 6'-dihydroxy-4'-methoxychalcone by entrapment in poly(D,L-lactide) nanoparticles.

The inhibition of intracellular Leishmania amazonensis growth by 2', 6'-dihydroxy-4'-methoxychalcone (DMC) isolated from Piper aduncum was further enhanced after encapsulation of DMC in polymeric nanoparticles. Encapsulated DMC also showed increased antileishmanial activity in infected BALB/c mice, as evidenced by significantly smaller lesions and fewer parasites in the lesions.

Animals↗
PubMed1999

A multicenter randomized controlled trial of a liquid loperamide product versus placebo in the treatment of acute diarrhea in children.

This randomized, double-blind, placebo-controlled trial of 48 hours' duration conducted in 13 primary care ambulatory practices in the United States and Mexico was used to compare the efficacy and safety of loperamide with placebo for the treatment of acute diarrhea in children aged 2 through 11 years. Two hundred fifty-eight children with acute nonspecific diarrhea were enrolled. Children were randomly assigned to treatment with loperamide HCl 0.5 mg/5 mL (n = 130) or placebo (n = 128). The first dose of loperamide consisted of either 1.0 mg (children 2 through 5 years of age) or 2.0 mg (children 6 through 11 years of age) of study medication under the observation of study personnel. This was followed by 1 mg after each unformed stool, with a total daily dose of up to 3.0 mg in the children 2-5 years of age, 4.0 mg in the children 6-8 years of age, and 6.0 mg in the children 9-11 years of age. The primary outcome measures were time to last unformed stool, time to first unformed stool, number of unformed stools during six consecutive 8-hour periods, and overall rating of efficacy/acceptability. Secondary outcomes included abdominal pain/cramping, vomiting, and fever. Children who received loperamide had significantly shorter time to last unformed stool (p = 0.0017) and fewer numbers of unformed stools (p = 0.0237) than children who received placebo. The end-of-study overall efficacy/acceptability rating of loperamide was significantly better than for placebo (p = 0.0107). All other clinically important outcome measures related to diarrhea relief favored loperamide. There was no significant difference in the incidence of drug-related adverse events between treatment groups, although total adverse events were reported more frequently (p = 0.048) by the loperamide group (15%) compared with the placebo group (7%). In conclusion, this controlled study provides data demonstrating that at recommend doses, loperamide is well tolerated and significantly shortens the duration and severity of symptoms of acute nonspecific diarrhea in children 2 through 11 years of age.

Acute Disease↗
PubMed1999

The changing face of Pneumocystis carinii pneumonia in AIDS patients.

The classic presentation of PCP is a bilateral interstitial pattern, which may be characterized as finely granular, reticular, or ground-glass opacities. When chest radiographic findings are normal or equivocal, high-resolution CT may be helpful because it is more sensitive than chest radiography for detecting PCP. The typical CT finding is extensive ground-glass attenuation. The face of PCP is changing. The classic radiographic presentation is being encountered less frequently. Increasingly recognized characteristic patterns of PCP include cystic lung disease, spontaneous pneumothorax, and an upper lobe distribution of parenchymal opacities. The spectrum of abnormalities associated with PCP is broadening and now includes abnormalities of the lung parenchyma, airways, lymph nodes, and pleura. An awareness of the varied presentations of PCP is important because the radiologist is often the first to suggest the diagnosis of PCP.

AIDS-Related Opportunistic Infections↗
PubMed1998

Determination of somatic mutant frequencies at glycophorin A and T-cell receptor loci for biodosimetry of prolonged irradiation.

PURPOSE: To determine the variant frequencies (VF) at glycophorin A (GPA) and T-cell receptor (TCR) loci in persons exposed to prolonged ionizing radiation at different doses and to assess the significance of the GPA and TCR assays for biodosimetry of prolonged irradiation. MATERIALS AND METHODS: The VF values were determined by means of flow cytometry in 120 persons exposed between 1968-1996. Most exposures were in Chernobyl clean-up workers in 1986-1987. RESULTS: A significant correlation was shown between the NO GPA variant cell frequency and dose (r = 0.61, p < 0.0001). The slope of the linear regression was 6.3 x 10(-6) NO mutant cells/Gy. Dose-dependent increase in the TCR VF was found in the group with recent exposures (slope 2.1 x 10(-4) variant cells/Gy, r = 0.75, p = 0.0002). In the Chernobyl clean up workers who received doses less than 0.25 Gy the TCR VF unlike the GPA VF was significantly higher than in the control non-irradiated individuals (p < 0.01 and p > 0.05 respectively). CONCLUSIONS: The GPA assay has limited potential to be used as a biodosimeter of prolonged irradiation, at least in dose interval up to 2.0 Gy. The TCR assay is likely to have greater potential in estimation of recent radiation exposure than the GPA assay.

Adult↗
PubMed1998

Clinically inapparent tuboovarian actinomycosis in a woman with an IUD. A case report.

BACKGROUND: The consequences and management of asymptomatic Actinomyces-like organisms detected on cervical cytologic smears continue to be controversial. CASE: A unilateral tuboovarian actinomycotic abscess was discovered in a woman who had undergone a hysterectomy for uterine leiomyomas. She had had an intrauterine device in place for many years without any symptoms of pelvic inflammatory disease. CONCLUSION: Ascending infection of the upper genital tract by Actinomyces may be clinically inapparent. When Actinomyces-like organisms aer detected on cervical cytologic smears, removal of an intrauterine device should be considered.

Actinomyces↗
PubMed1997

Development of a Tier I screening battery for detecting endocrine-active compounds (EACs).

One of the components of our research program is development of a mode-of-action screening battery to detect several different types of endocrine-active compounds (EACs). Our working hypothesis is that a comprehensive short-term in vivo/in vitro battery can be developed to identify endocrine toxicants using a collection of endpoints. The goals of this battery are that it be quick, cost effective, and predictive. The purpose of this battery is to identify potential EACs and to assess their potency in order to prioritize compounds for further study. Two in vivo screens (intact male and ovariectomized female rats) are being evaluated for their ability to detect several different types of endocrine activity. To validate this screen, 15 compounds with known endocrine activities are being used to evaluate a collection of different endpoints for their variability, stability over time, predictiveness, and dose dependency. These positive controls were chosen because they can modulate development, reproduction, or cancer. The advantage of an in vivo screen is that it utilizes a metabolically and physiologically intact system. The male in vivo battery will be used to assess several different types of endocrine activity, primarily by using a comprehensive hormonal battery. The female in vivo battery will be used to identify compounds which are either estrogenic/antiestrogenic or can alter the prolactin pathway. The in vitro portion of the screening battery consists of a yeast transactivation system (YTS). The YTS is being evaluated for its ability to identify compounds which are agonists or antagonists to the estrogen, androgen, or progesterone receptors. The expression of mammalian receptors in yeast allows for assessment of steroid-dependent transcriptional activators. The value of this system is that it can be used as a routine screen for compounds that interact with steroid receptors. Alterations in ligand binding to these receptors can be correlated with alterations in development via masculinization of females and/or feminization of males, decreases in reproductive success, or modulation of cancer incidence from in vivo tests. The in vivo and in vitro screens are designed to be run in parallel with built-in redundancy in order to reduce the probability of false-negative/ positive responses.

Animals↗
PubMed1996

Primary pulmonary sarcoma with morphologic features of monophasic synovial sarcoma and chromosome translocation t(X; 18).

The authors report an unusual spindle cell sarcoma that arose in the lung of a 12-year-old girl. This tumor had histologic, immunophenotypic, and ultrastructural features consistent with monophasic fibrous synovial sarcoma. These features included a growth pattern of densely packed spindle cells in irregularly intersecting, broad fascicles, diffuse vimentin immunoreactivity, and focal expression of epithelial membrane antigen and S100 protein. This diagnosis was further supported by cytogenetic studies showing the specific t(X; 18) chromosomal translocation associated with synovial sarcoma. This balanced translocation appears to be an essentially universal characteristic of these sarcomas, regardless of histologic subtype or site of origin. The constellation of morphologic and cytogenetic findings in this case firmly establishes synovial sarcoma as a subtype of pulmonary spindle cell sarcomas. The distinctive features of these neoplasms allow them to be distinguished from a variety of primary and metastatic malignancies in the lung.

Child↗
PubMed1996

Adenomatoid tumors of the pleura.

We report two cases of small pleural nodules showing the distinctive histologic appearance of adenomatoid tumor. Both lesions were discovered incidentally during surgery in patients undergoing lung resection for unrelated intrapulmonary masses: lung carcinoma in one case and histoplasmosis in the other. The tumors were composed of a focal proliferation of epithelioid cells forming vacuoles and tubular spaces in a fibrous stroma, as seen in adenomatoid tumors from other sites. The differential diagnosis in both cases included metastatic signet ring cell carcinoma. The mesothelial nature of the lesions was supported by immunohistochemical and ultrastructural evidence. The tumor cells in both cases were positive for cytokeratin but negative for carcinoembryonic antigen and LeuM1. One case was also negative for BER-EP4, B72.3, CD34, and Factor VIII. Electron microscopy in this case demonstrated well-developed basal laminae, desmosomes, and numerous slender microvilli along the luminal surfaces of the tumor cells. Adenomatoid tumors are regarded as a benign variant of mesothelioma. Despite the abundance of mesothelial cells in the pleura, adenomatoid tumors are apparently extremely rare in this location. Separation from malignant lesions such as adenocarcinoma and epithelioid hemangioendothelioma is important.

Adenomatoid Tumor↗
PubMed1995

Antibacterial phloroglucinols and flavonoids from Hypericum brasiliense.

Three known phloroglucinols (japonicine A, uliginosin A and isouliginosin B) and a new phloroglucinol (hyperbrasiol A) have been isolated from a petrol extract of the leaves and flowers of Hypericum brasiliense. Their structures were established by spectroscopic methods (UV, DCI-MS, 1H and 13CNMR, including SINEPT, HMBC, HSQC, DQFCOSY experiments). The substitution pattern of hyperbrasilol A was confirmed by X-ray crystallography. All four phloroglucinols were antibacterial against Bacillus subtilis in a TLC bioautographic assay. The flavonoids, kaempferol, luteolin, quercetin, quercitrin, isoquercitrin, hyperoside and guaijaverin, were isolated from a methanol extract of the same organs.

Anti-Bacterial Agents↗
PubMed1994

An antifungal gamma-pyrone and xanthones with monoamine oxidase inhibitory activity from Hypericum brasiliense.

A new gamma-pyrone (hyperbrasilone), three known xanthones (1,5-dihydroxyxanthone, 5-hydroxy-1-methoxyxanthone and 6-deoxyjacareubin) and betulinic acid have been isolated from a dichloromethane extract of stems and roots of Hypericum brasiliense. Their structures were established by spectroscopic methods (UV, EI-MS, 1H and 13C NMR) and that of the gamma-pyrone was confirmed by X-ray crystallography. Hyperbrasilone and the xanthones were all antifungal against Cladosporium cucumerinum, while the three xanthones showed differing degrees of inhibition of monoamine oxidase A and B.

Animals↗
PubMed1994

Clonal analysis of posttransplant lymphoproliferative disorders, using both episomal Epstein-Barr virus and immunoglobulin genes as markers.

The authors analyzed the clonality of 15 samples of B-cell lymphoproliferations arising in eight organ allograft recipients, using immunoglobulin (Ig) gene rearrangement and the fused terminal fragment of episomal Epstein-Barr virus (EBV) DNA as independent clonal markers. The tumors arose from 1 month to 4 years following transplantation. All tumors were monomorphous, high-grade lymphomas of immunoblastic (6 cases), large-cell noncleaved (centroblastic, 1 case), or small noncleaved (1 case) type. All tumors were highly aggressive and failed to respond to decreased immunosuppression alone. Each tumor had clonal Ig gene rearrangements, including those that were negative for surface Ig. In 13 of 15 specimens (seven of the eight cases), the tumors also contained latent, circularized EBV genome. In 10 specimens from six patients, the tumors contained a single predominant form of episomal EBV DNA, indicating clonal cellular proliferation of an EBV-infected progenitor cell. Three specimens from one patient showed more than one band of episomal EBV DNA, suggesting oligoclonal expansion, despite the detection of only a single clone by Ig gene rearrangement. Linear replicating EBV DNA was not detected in any of the cases. Synchronous or metachronous specimens from multiple sites were studied in five patients, four of which were EBV-positive cases. Two patients had identical Ig gene arrangements in each specimen, indicating a single neoplastic clone at all sites; one case was EBV-negative, and the other had identical EBV episomes in each specimen. In the other three cases, apparently different Ig gene rearrangements were found at different sites. In two of these, however, the same predominant EBV episome was present at each site, indicating a common clonal origin. The third case had oligoclonal EBV bands in each specimen, with distinct patterns in at least two different sites, suggesting true multiclonality. Analysis of EBV genomes is a useful adjunct to Ig gene analysis in assessing the clonality of these lesions.

Adult↗
PubMed1994

Unusual external resorption of a maxillary lateral.

This article defines an unusual previously unreported entity afflicting a maxillary lateral incisor. Labial idiopathic external root resorption just apical to the cemento-enamel presented as a gingival (periodontal) problem and was misinterpreted as cervical dental caries. This report defines a new possibility for a radicular defect in a maxillary lateral incisor that may cause periodontal problems.

Adult↗
PubMed1993

T-cell lymphoma of the vulva in a renal allograft recipient with associated hemophagocytosis.

The risk of B-cell lymphoma is greatly increased in transplant patients, whereas T-cell lymphomas have only rarely been reported in these patients. Although T-cell lymphomas in nonimmunosuppressed patients may be associated with either human T-cell lymphotropic virus type I (HTLV-I) or Epstein-Barr virus (EBV), these viruses have not been reported in association with post-transplant T-cell lymphoma. We report a case of T-cell lymphoma of the vulva arising in a renal allograft recipient receiving azathioprine and prednisone. The unusual clinical presentation led to difficulty in diagnosis because of a resemblance to either an infectious process or squamous cell carcinoma. The large cell lymphoma involved the dermis and subcutaneous fat of the vulva and was associated with hemophagocytosis in lymph nodes and bone marrow. The tumor had a mature, aberrant T-cell immunophenotype (CD3+ CD4+ CD7+ CD2- CD5- CD30+). Rearrangement of the T-cell receptor beta and gamma chain genes was found, but there was no evidence of either EBV or HTLV-I genomes. This case adds to the clinical and morphologic spectrum of T-cell lymphomas reported in allograft recipients and suggests that known lymphotropic viruses do not commonly have a role in post-transplant T-cell lymphoma.

Antigens, CD↗
PubMed1993

Pharmacological profile of epiyangambin: a furofuran lignan with PAF antagonist activity.

The ability of a furofuran lignan, epiyangambin, to inhibit PAF-induced rabbit platelet aggregation in vitro and thrombocytopenia in rats was investigated. Epiyangambin dose-dependently inhibited PAF-induced platelet aggregation without modifying the amplitude of the maximal response, indicating a competitive antagonism. The IC50 value of epiyangambin for 10(-9) M PAF-induced aggregation was 6.1 x 10(-7) M and the Schild analysis provided a pA2 of 6.91 +/- 0.2 with a slope of 0.98 +/- 0.25 (n = 4) and a pKb of 6.94 +/- 0.19. Epiyangambin had no effect upon the platelet aggregation induced by collagen, thrombin or ADP. The in vivo administration of the lignan at 20 mg/kg significantly inhibited PAF-induced thrombocytopenia in rats. These data indicate that epiyangambin is a potent and selective antagonist of PAF both in vitro and in vivo.

Animals↗