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Biomedical subjects

S R Plotkin

Publications and source records attributed to S R Plotkin.

12 recordsLinked to original sources
PubMed2005

Diagnostic criteria for schwannomatosis.

The neurofibromatoses are a diverse group of genetic conditions that share a predisposition to the development of tumors of the nerve sheath. Schwannomatosis is a recently recognized third major form of neurofibromatosis (NF) that causes multiple schwannomas without vestibular tumors diagnostic of NF2. Patients with schwannomatosis represent 2.4 to 5% of all patients requiring schwannoma resection and approximately one third of patients with schwannomatosis have anatomically localized disease with tumors limited to a single limb or segment of spine. Epidemiologic studies suggest that schwannomatosis is as common as NF2, but that familial occurrence is inexplicably rare. Patients with schwannomatosis overwhelmingly present with pain, and pain remains the primary clinical problem and indication for surgery. Diagnostic criteria for schwannomatosis are needed for both clinicians and researchers, but final diagnostic certainly will await the identification of the schwannomatosis locus itself.

Diagnosis, Differential↗
PubMed2001

Withdrawal from alcohol in withdrawal seizure-prone and -resistant mice: evidence for enkephalin resistance.

Methionine enkephalin (Met-enkephalin) functions as an endogenous anticonvulsant. Peptide transport system-1 (PTS-1) is an important regulator of Met-enkephalin levels in brain and transports the peptide from brain to blood. In outbred mice, alcohol dependence is associated with decreased PTS-1 activity and increased levels of Met-enkephalin. In contrast, alcohol withdrawal is associated with recovery of PTS-1 activity, decreased levels of Met-enkephalin, and seizures. In this study, we examined the PTS-1/Met-enkephalin system in two replicates of withdrawal seizure-resistant (WSR) and withdrawal seizure-prone (WSP) mouse lines. We measured levels of preproenkephalin (PPE) mRNA and Met-enkephalin peptide in brain and the activity of PTS-1 during alcohol-naive, -dependent, and -withdrawal states. In alcohol-naive animals, Met-enkephalin levels were higher in WSP than in WSR mice. In alcohol-withdrawal animals, Met-enkephalin levels remained elevated in WSP mice, whereas they increased in WSR mice. Peptide levels were unrelated to levels of PPE mRNA or activity of PTS-1. Factorial analysis showed that proneness to seizures was genetically linked to Met-enkephalin levels in alcohol-naive, -dependent, and -withdrawing mice but not to mRNA levels or PTS-1 activity. Overall, these results may be explained by resistance to enkephalin in WSP mice and suggest that the dysregulation of the PTS-1/Met-enkephalin system contributes to susceptibility to seizures in WSP mice.

Aluminum↗
PubMed2001

Primary nervous-system lymphoma.

Primary nervous-system lymphoma is a rare type of non-Hodgkin lymphoma, which is confined to the nervous system. This disease is managed quite differently from the usual treatment of either primary brain tumours or systemic non-Hodgkin lymphoma. Although whole-brain radiotherapy results in responses in more than 90% of cases, this treatment is associated with high relapse rates and with delayed neurotoxicity in elderly patients. First-generation chemotherapy regimens used successfully in systemic non-Hodgkin lymphoma (eg cyclo-phosphamide, adriamycin, vincristine, and prednisone) are ineffective in primary nervous-system lymphoma, partly because of the blood-brain barrier. Median survival of patients treated with radiotherapy alone or chemotherapy plus radiotherapy is similar, and ranges from 10 to 16 months. The addition of methotrexate-based chemotherapy has improved survival for these patients, extending median survival to more than 30 months. When used alone, methotrexate-based chemotherapy is associated with significantly fewer treatment-associated toxic effects. Leptomeningeal lymphoma and intraocular lymphoma are topics of particular relevance in primary nervous-system lymphoma and are addressed in this review.

Age Factors↗
PubMed2001

Advances in the therapy of primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma (NHL) confined to the nervous system. The management of PCNSL is quite different from the usual treatment of either primary brain tumors or systemic NHL. First-generation chemotherapy regimens used successfully in systemic NHL are ineffective in PCNSL, in large part due to the existence of the blood-brain barrier. Whole-brain radiation therapy (WBRT) results in high response rates but rapid relapse, and this treatment is associated with delayed neurotoxicity in patients with PCNSL. The addition of methotrexate-based chemotherapy has improved survival and lessened toxicity for this patient population. Fundamental issues that remain unresolved in PCNSL include identification of the optimal chemotherapy regimen for newly diagnosed and relapsed PCNSL, the role of WBRT and intrathecal chemotherapy in the treatment of PCNSL, and the optimal management of intraocular lymphoma. Finally, the optimal clinical study design for this rare disease has yet to be defined and implemented.

Brain Neoplasms↗
PubMed2000

Differential transport of rat and human interleukin-1alpha across the blood-brain barrier and blood-testis barrier in rats.

Human interleukin-1alpha is transported across the murine blood-brain barrier (BBB) and blood-testis barrier (BTB) by a saturable transport system. Differences in the biological activity and binding of human IL-1 in mouse and rat brain raise the possibility of species differences in the transport of IL-1 across the BBB and BTB. We measured the transport of recombinant human 125I-IL-1alpha (I-huIL-1alpha) and rat 125I-IL-1alpha (I-ratIL-1alpha) across the rat BBB and BTB after intravenous injection using a sensitive in vivo technique and film autoradiography. I-ratIL-1alpha was found to cross the rat BBB and rat BTB at rates comparable to those reported previously for murine IL-1alpha in mice. Passage across the BBB was inhibited by the addition of unlabeled rat IL-1alpha, demonstrating saturable transport. In contrast, I-huIL-1alpha entered the brain of the rat much more slowly, and its entry was not inhibited by the addition of unlabeled human IL-1alpha. These results show that the rat interleukin-1 transporter, unlike the murine transporter, does not transport human IL-1alpha. This difference highlights the importance of species specificity in IL-1alpha transport and may partly explain the different physiological responses to exogenous human IL-1alpha among rodent species.

Animals↗
PubMed1999

Folk remedy use in the inner city.

BACKGROUND: Folk remedies (FRs) are common in some minority communities within the United States. However, little information is available about the use of FRs in the inner city. The objectives of this study were to identify the prevalence and types of FRs used in the inner city, to characterize the population using FRs, and to study patient attitudes toward discussing FRs with physicians. METHODS: We interviewed 71 patients over the age of 18 who visited an inner city ambulatory clinic. RESULTS: The rate of FR use ranged from 10% to 50% among common medical conditions, with most patients (59%) using at least one remedy. Folk remedy use did not correlate with patient age. Most patients used FRs because they believed them to be efficacious, and most felt comfortable discussing FRs with their physicians. CONCLUSIONS: Inner city residents of all ages use FRs to treat illness. These FRs are benign and consist of common household items. Health care workers should feel comfortable discussing FRs with their patients since their patients are comfortable with the topic.

Adolescent↗
PubMed1998

Enkephalin, PPE mRNA, and PTS-1 in alcohol withdrawal seizure-prone and -resistant mice.

Inbred animal strains provide an opportunity to study genetic factors in alcoholism in the absence of environmental factors. Although the concentration of methionine enkephalin (Met-enkephalin) in whole brain has been implicated in the consumption of ethanol, it has not been studied in the brains of alcohol withdrawal seizure-prone (WSP) and withdrawal seizure-resistant (WSR) mice. We compared these concentrations with the levels of preproenkephalin (PPE) mRNA and with the activity of peptide transport system-1 (PTS-1), a brain-to-blood transport system for Met-enkephalin that is affected by ethanol. The concentrations of Met-enkephalin were significantly greater in WSP mice than in WSR mice, whereas synthesis of Met-enkephalin, as reflected by PPE mRNA levels, and transport out of the brain by PTS-1 was not different. These results support a direct link between elevated concentrations of Met-enkephalin in whole brain and proneness to withdrawal-induced seizures. We suggest that the inverse relationship between the consumption of ethanol and proneness to seizures in inbred mice can be explained through their opposite relationships to Met-enkephalin.

Animals↗
PubMed1997

Ethanol alters the concentration of Met-enkephalin in brain by affecting peptide transport system-1 independent of preproenkephalin mRNA.

Alcohol-related events have been proposed to be under neurochemical control. For example, the concentration of methionine enkephalin (Met-enkephalin) in brain has been inversely correlated with ethanol consumption in alcohol-preferring and alcohol-nonpreferring mice. The concentrations of Met-enkephalin are controlled in part by peptide transport system-1 (PTS-1), a brain-to-blood transport system for Met-enkephalin located at the blood-brain barrier. We examined the relationships among concentrations of Met-enkephalin, preproenkephalin (PPE) mRNA, and PTS-1 activity in mice exposed to ethanol. PTS-1 activity decreased progressively during the process of addiction and then partially recovered within hours after withdrawal of ethanol. Serotonin lost its ability to modulate PTS-1 activity in exposed mice, indicating that regulation of PTS-1 activity was affected by ethanol. Concentrations of Met-enkephalin tended to move in the opposite direction from PTS-1 activity, increasing significantly with addiction. In naive mice, PPE mRNA levels correlated with the concentrations of Met-enkephalin. However, levels of PPE mRNA remained unchanged during addiction, withdrawal, and recovery, no longer correlating with concentrations of Met-enkephalin. These results suggest that ethanol affects concentrations of Met-enkephalin in brain through post-transcriptional mechanisms and that PTS-1 activity is one of those mechanisms.

Animals↗
PubMed1996

Comparison of saturable transport and extracellular pathways in the passage of interleukin-1 alpha across the blood-brain barrier.

Blood-borne cytokines enter the brain by transport across the blood-brain barrier (BBB) or by leakage through extracellular pathways at sites, such as circumventricular organs (CVOs), without a BBB. We used radioactively labeled albumin (T-Alb) to differentiate the relative contribution of transport and extracellular pathways to the passage of interleukin-1 alpha ([125I]IL-1 alpha) across the BBB. The major mechanism of entry for [125I]IL-1 alpha after intravenous (i.v.) injection was a saturable transport system with extracellular pathways accounting for only a small fraction of entry into brain. CVOs concentrated blood-borne [125I]IL-1 alpha in a saturable manner to a much greater extent than did the cerebral cortex and cerebellum, but accounted for less that 5% of total brain uptake. After intracerebroventricular (i.c.v.) injection, [125I]IL-1 alpha and T-Alb were concentrated in the CVOs, especially the median eminence, although CVOs contained less that 1% of the substances injected. Distribution after i.c.v. injection was largely due to diffusion and leakage through extracellular pathways. We conclude that after i.c.v. injection, leakage across extracellular pathways accounts for the small but concentrated amount of [125I]IL-1 alpha found in CVOs. After i.v. injection, transport across the BBB accounts for the majority of [125I]IL-1 alpha in brain.

Albumins↗
PubMed1991

Human interleukin (IL) 1 alpha, murine IL-1 alpha and murine IL-1 beta are transported from blood to brain in the mouse by a shared saturable mechanism.

Interleukins (ILs) 1 alpha and 1 beta are important components of the neuroimmune axis. Recent work has shown that human 125I-IL-1 alpha can enter the brain from the blood by a saturable system, suggesting a mechanism that may directly link the immune and nervous systems. Here, it is shown that radioiodinated murine IL-1 beta and especially murine IL-1 alpha are even more rapidly transported into the brain of the mouse than is radioiodinated human IL-1 alpha after i.v. injection. All three cytokines exhibited self-inhibition, thus demonstrating saturable transport. Also, they all cross-inhibited the transport of each other. This shows that there are not three separate transport systems, but that they either share transport systems with overlapping affinities or share a single system. It was calculated that 0.06% to 0.08% of the dose of human 125I-IL-1 alpha injected i.v. was present in the brain during the first 60 min. By contrast, no saturable component could be detected in the brain to blood passage of the three ILs. No disruption of the blood-brain barrier to radioactively labeled albumin was found with i.v. doses of up to 50 micrograms/kg of human IL-1 alpha. Additional studies on the blood to brain transport of human 125I-IL-1 alpha showed no modification by dexamethasone, morphine, indomethacin or alpha-melanocyte stimulating hormone. Studies with antibodies directed toward the binding or nonbinding sites of IL or its receptor on the murine T lymphocyte suggest similar, but not identical, structural requirements for transport and for receptor binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Permeability of the blood-brain barrier to soluble cytokine receptors.

Soluble receptors for cytokines can be important regulators of cytokine function. By binding to their cytokine ligands, they act as antagonists and carrier proteins. We investigated whether the blood-to-brain saturable transport of human tumor necrosis factor-alpha (TNF) and human interleukin-1 alpha (IL-1) radioactively labeled with 125I could be blocked by preincubation with their soluble receptors. At ratios of 100:1 and 1,000:1 of receptor to cytokine, the soluble p75 human receptor to TNF (rhuTNFR:Fc) totally blocked the entry of human or murine TNF into the brain. However, the soluble murine receptor to IL-1 (muIL-1R) only partially blocked IL-1 entry. Radioactively labeled rhuTNFR:Fc and muIL-1R were not transported across the blood-brain barrier (BBB) and were no more able to penetrate the BBB than the vascular marker serum albumin. This indicates that the transporter at the BBB for IL-1, but not the one for TNF, can strip the cytokine from its soluble receptor. These findings might be useful in determining which, if any, of the actions exerted on the brain by blood-borne cytokines are due to penetration of the BBB.

Animals↗