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Biomedical subjects

J S Hong

Publications and source records attributed to J S Hong.

At least 19 recordsLinked to original sources
PubMed1995

Selective killing of cholinergic neurons by microglial activation in basal forebrain mixed neuronal/glial cultures.

Microglia activation by lipopolysaccharides (LPS) significantly decreased choline acetyltransferase-immunopositive (ChAT+) neuron number and ChAT activity in rat primary basal forebrain mixed neuronal/glial cultures. The number of non-cholinergic (ChAT(-)) neurons was unaffected. LPS induced nitric oxide synthase (NOS) in microglia, increased the media level of the NO metabolite nitrite, and the NOS inhibitor Ng-nitro-L-arginine methylester (NAME) protected the ChAT+ neurons from LPS. The combination of beta-amyloid peptide (1-42) and interferon-gamma (INF-gamma) also increased the media nitrite level and decreased ChAT+ neuron number. Cholinergic neurons are lost early in the course of Alzheimer's disease, and the enhanced sensitivity of these neurons to microglial activation in mixed neuronal/glial culture may be useful for modeling Alzheimer's disease and developing therapeutic strategies to combat this disease.

Amyloid beta-Peptides↗
PubMed1995

Selective inhibitors of Candida albicans dihydrofolate reductase: activity and selectivity of 5-(arylthio)-2,4-diaminoquinazolines.

The recent increase in fungal infections, especially among AIDS patients, has resulted in the need for more effective antifungal agents. In our search for such agents, we focused on developing compounds which inhibit fungal dihydrofolate reductase (DHFR). A series of 25 5-(arylthio)-2,4-diaminoquinazolines were synthesized as potentially selective inhibitors of Candida albicans DHFR. The majority of the compounds were potent inhibitors of C. albicans DHFR and much less active against human DHFR. High selectivity, as defined by the ratio of the I50 values for human and C. albicans DHFR, was achieved by compounds with bulky and rigid 4-substituents in the phenylthio moiety. For example, 5-[(4-morpholinophenyl)thio]-2,4-diaminoquinazoline displayed a selectivity ratio of 540 and was the most selective inhibitor synthesized to date. Substitution in the 2- or 3-position of the 5-phenylthio group provided only marginal selectivity. 6-Substituted-5-[(4-tert-butylphenyl)thio]-2,4-diaminoquinazolines showed potent activity against the C. albicans enzyme but were equally active against human DHFR. Most of the selective compounds were also good inhibitors of C. albicans cell growth, with minimum inhibitory concentration values as low as 0.05 microgram/ mL.

Animals↗
PubMed1995

DNA binding activity of CREB transcription factors during ontogeny of the central nervous system.

During the early postnatal period, the rat brain contains high basal levels of AP-1 DNA binding activity which declines to the low levels found in the adult by the third postnatal week. Although the individual transcription factors that comprise this AP-1 DNA binding complex had not been identified, we discovered that these proteins were immunoreactive to the cAMP responsive element binding protein (CREB) and also recognized the CRE element. The 45 kDa CREB-immunoreactive protein was detected at high levels only during the first postnatal week. CRE and AP-1 DNA binding activities were studied in the olfactory bulb, striatum, hindbrain, hippocampus, hypothalamus and cerebellum. In general, the DNA binding activity correlated with the stage of maturation of the particular brain region. However, basal AP-1 DNA binding in the olfactory bulb from adults remained slightly elevated relative to other brain regions. Interestingly, the DNA binding complex in the olfactory bulb began to include fos-related antigen as well as CREB by the third postnatal week. The fra-containing complex only recognizes the AP-1 element, while the CREB complex can bind to either CRE or AP-1 sequences. Thus, there is crosstalk between the signal transduction systems that activate CREB and AP-1 transcription factors. This elevated CREB DNA binding activity may be a sensitive index for studying the development of the brain and could be involved in modulating the genomic program in differentiating cells.

Aging↗
PubMed1995

Modulatory effects of [Met5]-enkephalin on interleukin-1 beta secretion from microglia in mixed brain cell cultures.

In the present study, functional interactions between [Met5]-enkephalin (ME), naloxone and lipopolysaccharide (LPS) on interleukin-1 beta (IL-1 beta) immunostaining and secretion have been assessed in mixed brain cell cultures from embryonic day 17 mice. Adding ME alone or together with LPS to the culture increased the release of IL-1 beta after 48 h in a concentration-dependent fashion. In situ hybridization studies showed that LPS, but not ME, increased the abundance of IL-1 beta mRNA. The enhanced release of IL-1 beta caused by ME or LPS was partially blocked by naloxone. LPS induced concentration-dependent morphological changes in microglia in mixed brain cell cultures, identified by a monoclonal antibody F4/80 which is specific for macrophages/microglia. Despite increasing IL-1 beta release into the media, ME (10(-8) M) did not induce morphological changes in microglia. Naloxone alone also had no effect on glial morphology; however, the LPS-induced morphological changes were blocked by naloxone. Our data indicate that both exogenous and endogenous opioids regulate IL-1 beta production by microglial cells in the mixed brain cell cultures.

Animals↗
PubMed1995

beta-Endorphin enhances the replication of neurotropic human immunodeficiency virus in fetal perivascular microglia.

The effect of an endogenous opiate, beta-endorphin, on the replication of HIV was investigated in brain perivascular microglia. Beta-endorphin enhanced the synthesis of p-24 antigen and transactivation of HIV promoter. Dialysed culture supernatants of endorphin-treated microglia re-activated latent HIV infection. These culture supernatants showed elevated levels of interleukin-1 beta, IL-6 and tumor necrosis factor alpha. Sub-optimal concentration of beta-endorphin potentiated GP-120-induced synthesis of these cytokines. Nalaxone reversed beta-endorphin-induced, but not GP-120-induced, cytokine production and enhanced HIV replication. These results suggest that endogenous opiates may contribute to the progression of AIDS dementia complex.

Cytokines↗
PubMed1995

Acute repeated nicotine injections increase enkephalin and decrease AP-1 DNA binding activity in rat adrenal medulla.

Previously we reported that a single injection of nicotine decreased AP-1 DNA binding activity in adrenal medullae, although chronic bidaily nicotine (and saline) injections increased this binding activity [15]. Repeated acute nicotine injections (3 mg/kg i.p., 7 injections equi-spaced over a 3 h period) effectively increased adrenal tyrosine hydroxylase [3] and [Met5]enkephalin levels and also profoundly decreased adrenal medulla AP-1 DNA binding activity for over 8 h.

Adrenal Medulla↗
PubMed1995

Implications of prolonged expression of Fos-related antigens.

The AP-1 transcription factors are composed of the Fos and Fos-related antigens as well as Jun and related proteins. These factors have been extensively studied in many diverse paradigms using acute stimuli. Recent attention has focussed on long-term elevation of Fos-related antigens in the CNS, and this is discussed by Keith Pennypacker, Jau-S. Hong and Michael McMillian. Repeated or chronic treatment elevates Fos-related antigen levels for days in many different brain regions. Both direct and indirect stimulation are responsible for the protracted increase in Fos-related antigen-immunoreactive proteins, which may modulate late onset genes involved in neuroplasticity. Understanding the role of these factors in long-lasting or permanent disease states may provide insight into potential therapeutic strategies to treat chronic CNS disorders.

Animals↗
PubMed1995

Expression of the proenkephalin A gene and [Met5]-enkephalin secretion induced by arachidonic acid in bovine adrenal medullary chromaffin cells: involvement of second messengers.

We have previously reported that arachidonic acid (AA) increases the long-term secretion of [Met5]-enkephalin (ME) and the expression of proenkephalin A (proENK) mRNA in bovine adrenal medullary chromaffin (BAMC) cells. To characterize the underlying signal transductional mechanisms for the AA-induced responses, the interactions of AA with several second messenger systems were studied. Long-term (24-h) treatment with AA (100 microM) increased both the secretion of ME and the expression of proENK mRNA. Pretreatment of BAMC cells with nimodipine (1 microM), but not with omega-conotoxin GVIA (1 microM), inhibited the secretion of ME and the expression of proENK mRNA induced by AA. Calmidazolium (1 microM), a calmodulin antagonist, also significantly inhibited AA-induced responses. However, a protein kinase C (PKC) inhibitor, sphingosine (36 microM), was ineffective in blocking AA-induced responses. In addition, the down-regulation of PKC by phorbol 12-myristate 13-acetate (0.1 microM) for 48 h did not inhibit the AA-induced responses. Forskolin (5 microM), an adenyl cyclase activator, alone increased the secretion of ME as well as proENK mRNA levels and, when coincubated with AA, showed an additive effect on the secretion of ME and the levels of proENK mRNA. The results suggest that the Ca2+/calmodulin pathway, but not the protein kinase A or PKC pathway, is partially involved in mediating the AA-induced increases of the long-term secretion of ME and the levels of proENK mRNA.

Adrenal Medulla↗
PubMed1995

Effects of sulpiride and SCH 23390 on methamphetamine-induced changes in body temperature and lethality.

Data from human and animal studies suggest that hyperpyrexia contributes to both the neurotoxic and the lethal effects of stimulant drugs such as methamphetamine (METH). Because many of the effects of METH involve the release of dopamine from CNS neurons, we examined the effects of D1 and D2 dopamine receptor antagonists on METH-induced lethality and determined whether these effects correlated with changes in body temperature. In the first set of experiments, we found that the D2 antagonist sulpiride (SUL; 20, 40 or 80 mg/kg) potentiated the lethality caused by a single injection of METH (10 mg/kg). Pretreatment with the D1 antagonist SCH 23390 (SCH; 0.5 mg/kg) reduced the lethality induced by METH alone or by SUL/METH. Other D2 or 5-hydroxytryptamine antagonists prevented, rather than potentiated, METH-induced lethality. In a second set of experiments, rectal temperatures were recorded in METH-injected animals pretreated with SCH or SUL. METH caused a significant increase (i.e., above vehicle-injected levels) in body temperature at 2.5 hr after injection. The effects of SCH or SUL pretreatment on METH-induced changes in body temperature suggest that the lethality-potentiating and -protective effects of SUL and SCH, respectively, were not due to altered thermoregulatory responses. These data support the idea that D1 receptor activation is an important event in the lethality caused by METH and that SUL may potentiate D1 receptor activation by augmenting METH-induced DA release.

Animals↗
PubMed1994

Regulation of tyrosine hydroxylase in olfactory bulb cultures: selective inhibition of depolarization-induced increase by endogenous opioids.

Regulation of tyrosine hydroxylase (TH) by second messenger pathway activators was examined in rat olfactory bulb cell cultures. The number of TH-immunoreactive neurons was increased 2-3-fold by 36 h treatments with forskolin (Fsk, 10(-6) M) or phorbol myristate acetate (PMA, 10(-7) M), but was not significantly increased by a depolarizing concentration of KCl (45 mM). In contrast, KCl increased media [Met5]enkephalin (ME) immunoreactivity 2-fold in these cultures, equivalent to stimulation with Fsk or PMA. The possibility was examined that ME or another opioid produced by the cultures selectively inhibited the TH response to KCl. Pretreatment with the opioid receptor antagonist naloxone (10(-6) M) greatly increased the number of TH-immunoreactive neurons observed in response to KCl treatment, but had no effect on basal or Fsk-stimulated TH immunostaining, nor on basal or stimulated ME release. The increase in TH-immunoreactivity observed with combined KCl plus naloxone treatment was prevented by pretreating the cultures with the calcium channel blocker nimodipine (10(-6) M), which had no effect on Fsk stimulation or basal TH immunostaining. These data suggest that endogenous opioids selectively inhibit KCl-stimulated Ca2+ entry and thus TH induction in olfactory bulb cell cultures. These cultures offer a simple model system for further study of TH regulation in dopaminergic neurons.

Animals↗
PubMed1994

Brain injury in a dish: a model for reactive gliosis.

Reactive gliosis is a powerful response to brain injury and subsequent neuronal damage in vivo. Neuronal cell cultures are now well established as assays to study this process in vitro. However, equivalent studies of purified glial cell populations have only recently been achieved, following the realization that glial cells produce many of the neuropeptides, transmitters and growth factors that are produced also by neurons. There is now scope for studies in vitro that use mixed, identified populations of glial and neuronal cells to dissect the interactions between the two. Such cultures also lend themselves to assays for potential therapeutic strategies for brain injury that take account of all the different cell types found in the brain.

Animals↗
PubMed1994

A case of coincident multiple myeloma and non-Hodgkin's lymphoma.

A rare case of coexisting multiple myeloma and non-Hodgkin's lymphoma at the time of diagnosis is presented. The patient presented with petechiae, melena and weight loss. IgA lambda monoclonal gammopathy in the serum and free lambda chain in urine were documented. Bone marrow biopsy demonstrated an interstitial infiltration of neoplastic plasma cells coexisting with localized collection of neoplastic lymphoid cells composed of monotonous small lymphocytes with occasional cleaved nuclei. Immunophenotype of plasma cell was IgA lambda. The patient also had a jejunal mass, with biopsy proven malignant lymphoma, diffuse small cleaved cell type. The tumor was diffusely positive for pan-B marker. After chemotherapy, the IgA lambda monoclonal protein decreased and the patient improved. This case suggest, that the seound B-cell neoplasm may have evolved by transformation of an original neoplastic clone, or that malignant tumors may be polyclonal at onset. Definitive diagnosis and staging of each disorder is important for proper management.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Characterization of dynorphin-containing neurons on dissociated dentate gyrus cell cultures.

In the dentate gyrus, the synthesis of the opioid peptide, dynorphin, is modulated by a variety of stimuli. In order to elucidate the cellular and molecular mechanisms regulating the synthesis of dynorphin in the hippocampus, we have established a routine primary cell culture of dentate granule neurons and identified granule-like neurons by a characteristic marker, dynorphin, in these cultures. Cultures were prepared from 7-day-old rat pups and maintained in medium with 2% fetal bovine serum. These cultures contained approximately 20% neurons and survived for over 4 weeks. After 2 weeks in culture, neurons expressing dynorphin-A and its messenger RNA were detected using immunocytochemistry and in situ hybridization, respectively. In dentate cultures, enkephalin-, cholecystokinin-, neuropeptide Y- and substance P-positive cells were observed in addition to dynorphin-positive cells with immunocytochemistry. The results suggest that dentate gyrus cell cultures provide a valid in vitro model for studying molecular mechanisms regulating prodynorphin gene expression.

Animals↗
PubMed1992

Preferential activation of [3H]phorbol-12,13-dibutyrate binding by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) in neonatal striatal cell cultures.

Activation of excitatory amino acid receptors increased [3H]phorbol-12,13-dibutyrate ([3H]PdBu) binding in four week cultures of striatal cells from postnatal day 7 rat pups (PN7), and in PN7 cells co-cultured the fourth week with striatal cells from postnatal day 1 rat pups. Kainate (KA), trans-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD), and N-methyl-D-aspartate (NMDA) increased [3H]PdBu binding equally in both types of cultures, but alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) increased binding by 3-fold in the co-cultures. Thus, [3H]PdBu binding in these two types of striatal cultures offers a simple model system for studying the regulation of AMPA/KA receptor responses.

Animals↗
PubMed1992

Constitutive expression of AP-1 transcription factors in the rat adrenal. Effects of nicotine.

The AP-1 proteins (c-fos and fos-related antigens and jun proteins) are transcription factors that are induced in most cells by various stimuli, but the expression of these proteins is low or undetectable in the basal state. Our data indicate that the rat adrenal gland contains a basally expressed elevated level of AP-1 proteins and mRNAs (40- and 35-kDa fos-related antigens, a 39-kDa c-jun protein, c-jun, junB, and junD mRNA), as well as high basal AP-1 DNA binding activity. Both the medulla and cortex contained equivalent levels of fos-related antigens and c-jun protein; however, the majority of AP-1 DNA binding was detected in the medulla. Handling of rats for several days prior to sacrifice failed to affect protein expression or binding; on the other hand, repeated injections of nicotine increased AP-1 DNA binding. A single nicotine injection 60 min prior to removing the adrenals caused a significant reduction in AP-1 DNA binding without any detectable changes in AP-1 protein expression. Pretreatment of adrenal nuclear extracts with alkaline phosphatase prior to incubation with the AP-1 oligomer decreased binding activity. Thus, unlike most tissues where AP-1 DNA binding activity is controlled by increased expression of AP-1 proteins, DNA binding in the rat adrenal gland appears to be controlled at the post-translational level, possibly through dephosphorylation.

Adrenal Glands↗
PubMed1992

A 35 kDa Fos-related antigen is co-localized with substance P and dynorphin in striatal neurons.

The rat striatum after dopamine denervation followed by repeated apomorphine treatment was examined for the co-expression of c-fos and Fos-related antigens with dynorphin, substance P and [Met5]enkephalin using Western blot and immunohistochemical techniques. Administration of apomorphine, a dopamine agonist, elevated the level of 35 kDa Fos-related antigen which co-localized with dynorphin and substance P, but not enkephalin, in striatal neurons.

Animals↗