Biomedical subjects

A J Li

Publications and source records attributed to A J Li.

At least 19 recordsLinked to original sources

PubMed2001

Intracerebroventricular infusion of fibroblast growth factor-1 increases Fos immunoreactivity in periventricular astrocytes in rat hypothalamus.

When released into the third ventricle of the brain, fibroblast growth factor (FGF)-1 acts as a feeding suppressor. To identify the cells that respond to FGF-1 in this process, we investigated the effects of intracerebroventricular administration of FGF-1 on Fos protein expression in the rat hypothalamus. Two hours after infusion of FGF-1, significantly more Fos signals were observed in the periventricular zone of the third ventricle and its surroundings. Double immunohistochemical studies using antibodies against Fos, glial fibrillary acidic protein, and neuronal nuclei revealed that the FGF-1-induced Fos signals in the periventricular zone were in astrocytes, not in neurons. FGF-1-induced Fos expression was not found in neurons in such hypothalamic nuclei as the lateral hypothalamic area, paraventricular nucleus, ventromedial hypothalamic nucleus, dorsomedial hypothalamic nucleus, or arcuate nucleus. These results suggest a possible involvement of periventricular astrocytes in the early stages of FGF-1-induced feeding suppression.

Animals↗

PubMed2001

Pattern of lymph node metastases in clinically unilateral stage I invasive epithelial ovarian carcinomas.

PURPOSE: There is controversy regarding the pattern of lymphatic spread in unilateral stage I invasive ovarian carcinomas. The purpose of this study is to describe the incidence and distribution of lymph node (LN) metastases in ovarian carcinomas clinically confined to one ovary. METHODS: Ninety-six patients with disease visibly confined to one ovary were identified. Pathology reports were reviewed to identify metastatic LN involvement, number of involved nodes, and their locations. Patients with gross disease in the pelvis or abdomen or those who had grossly positive LNs removed for debulking were excluded from this review. RESULTS: Fourteen of ninety-six patients (15%) had microscopically positive LNs on pathologic review. All of these 14 patients had grade 3 tumors. Grade 3 tumors were more commonly seen in LN-positive versus LN-negative patients (P < 0.001). Pelvic nodes were positive in 7 patients (50%), paraaortic nodes in 5 patients (36%), and both in 2 patients (14%). Forty-two patients had LN sampling only on the side ipsilateral to the neoplastic ovary, 4 of whom (10%) had LN metastases. Fifty-four patients had bilateral sampling performed, 10 of whom (19%) had LN metastases. Of these 10 patients, isolated ipsilateral LN metastases were seen in 5 (50%) cases. Isolated contralateral LN metastases were seen in 3 (30%) cases, and bilateral metastases were seen in 2 (20%). CONCLUSIONS: In this cohort of patients with clinical stage I ovarian carcinoma with disease limited to one ovary, bilateral LN sampling increased the identification of nodal metastases. Ipsilateral sampling may result in the understaging of patients. Bilateral pelvic and paraaortic LN sampling is recommended to accurately stage ovarian carcinoma.

Aorta, Abdominal↗

PubMed2001

Genetic factors in ovarian carcinoma.

Recent evidence indicates that inherited and acquired genetic mutations are the driving force behind carcinogenesis and cellular transformation. This review examines a number of proto-oncogenes and tumor suppressor genes that are associated with ovarian carcinomas, including p53, BRCA1, and BRCA2; mismatch repair genes such as hMSH2 and hMLH1; and PTEN, HER-2/neu, K-ras, fms, and AKT2. Novel genes recently implicated in ovarian tumorigenesis are discussed, including NOEY2, OVCA1, and PIK3CA. Although no singular gene alteration has been shown to initiate transformation in the ovarian epithelium, elucidation of the complex molecular and cellular mechanisms involving these known gene mutations may result in new clinical management strategies.

BRCA1 Protein↗

PubMed2001

2-buten-4-olide, an endogenous feeding suppressant, improves spatial performance through brain acidic fibroblast growth factor in mice.

Endogenous sugar acid 2-buten-4-olide, a satiety substance, has been shown to increase the blood glucose, norepinephrine, and glucocorticoid concentrations that are known to modulate learning and memory processes. The glucose-induced release of acidic fibroblast growth factor facilitated the hippocampus-dependent memory function. In the present study, we investigated the effect of 2-buten-4-olide on the spatial performance of male DDY mice undergoing the water maze task. The intraperitoneal injection of 2-buten-4-olide (5 mg/kg) facilitated the spatial performance, which was indicated by a reduction in the escape latency in which the mouse finds and climbs the goal platform in comparison to the vehicle-injected control mice. In the probe test after removing the platform, the 2-buten-4-olide-treated mice stayed a longer time in the quadrant where the platform was originally located and crossed more frequently at the platform location than did the control mice. The pretreatment of acidic fibroblast growth factor antibody injected into the lateral ventricle eliminated the effect of 2-buten-4-olide both during the training sessions and during the probe test. Therefore, 2-buten-4-olide was found to improve the spatial performance, and this effect is mediated, at least in part, by acidic fibroblast growth factor.

4-Butyrolactone↗

PubMed2001

Feeding suppression by fibroblast growth factor-1 is accompanied by selective induction of heat shock protein 27 in hypothalamic astrocytes.

It has been suggested that fibroblast growth factor (FGF)-1 serves as a physiological satiety factor in the hypothalamus, although the molecular mechanism underlying such a function is poorly understood. To gain additional insight into this issue, we used a Sendai virus (SeV) gene expression system in rats to explore genes differentially expressed subsequent to expression of FGF-1. Using cDNA arrays, we determined that infusion of FGF-1/SeV into one lateral ventricle induced selective expression of heat shock protein (HSP) 27 in the hypothalamus. Whereas FGF-1 expression was restricted to the ependymal cell layer of the cerebral ventricles, HSP27 was more widely expressed in astrocytes residing in the surrounding periventricular region. Similarly, infusion of FGF-1 polypeptide into a lateral ventricle induced dose-dependent HSP27 expression in periventricular astrocytes surrounding the third ventricle, with maximum mRNA levels being attained 6 h after infusion. This induction of HSP27 was accompanied by a significant suppression of feeding behaviour. Interestingly, suppression of feeding caused by intracerebro ventricular infusion of ciliary neurotrophic factor was also accompanied by induction of HSP27 in periventricular astrocytes, but suppression of feeding caused by infusion of leptin was not. It therefore appears that suppression of feeding by FGF-1 is accompanied by selective induction of HSP27 expression in hypothalamic astrocytes surrounding the third ventricle, and that this response may be a key component of the mechanism by which appetite is regulated by FGF-1.

Animals↗

PubMed2000

Bacteriology and treatment of malodorous lower reproductive tract in gynecologic cancer patients.

OBJECTIVE: To determine the bacteriology of lower genital tract cancers to direct potential treatment modalities and to determine the impact of treatment on quality of life. METHODS: Gram stain, saline preparations, tumor pH determinations, and anaerobic and aerobic tumor cultures were obtained from 13 consecutive patients with malodorous gynecologic cancers and 13 patients (controls) with nonmalodorous tumors. All patients with odor were treated with topical metronidazole for 7 days. Odor assessment questionnaires were administered daily in the treatment group. Quality-of-life evaluation was assessed using the Functional Assessment of Cancer Therapy questionnaire before and after treatment. RESULTS: Cancer of the cervix (n = 21) was the most common primary site and accounted for 81% (95% confidence interval 61%, 93%) of malodorous gynecologic cancers. Eight of 13 (62%) patients with malodorous tumors had bacterial vaginosis compared with four of 13 (31%) of those without odor (P =.11). Aerobic and anaerobic bacteria were isolated with equal frequency from malodorous gynecologic cancers. Results of odor assessment questionnaires showed a graded improvement with topical antibiotic therapy (P <.001). The Functional Assessment of Cancer Therapy questionnaire indicated improved quality of life after therapy (P =.02). CONCLUSION: Most patients with odor had bacterial vaginosis and had an improvement in odor with topical metronidazole. Therefore, this treatment might be useful for patients with malodorous pelvic tumors.

Anti-Bacterial Agents↗

PubMed1999

Protective effect of acidic fibroblast growth factor against ischemia-induced learning and memory deficits in two tasks in gerbils.

The influence of transient forebrain ischemia on behavioral performance, and the effect of intracerebroventricular (i.c.v.) injection of acidic fibroblast growth factor (aFGF) on such ischemia-induced deficits were examined in Mongolian gerbils by assessing learning and memory in two tasks: passive avoidance and Morris water maze. A 5-min period of forebrain ischemia led to learning and memory deficits in both tasks, and also to neuronal death in the hippocampal CA1 region. Continuous i.c.v. infusion of aFGF bilaterally into the lateral ventricules by osmotic minipumps over 2 days before, and 5 days after the ischemia (a total of 3.6 microg/gerbil) largely prevented both the ischemia-induced behavioral deficits and the neuronal death in the hippocampus. These observations suggest that the hippocampus is a critical site for the performance of the two tasks, and that aFGF has a protective effect against such ischemia-induced learning and memory deficits in gerbils.

Amnesia↗

PubMed1999

Effects of an acidic fibroblast growth factor fragment analog on learning and memory and on medial septum cholinergic neurons in senescence-accelerated mice.

We examined the effects of repeated subcutaneous injections of an acidic fibroblast growth factor fragment analog, [Ala16] acidic fibroblast growth factor (1-29), on learning and memory and on the choline acetyltransferase immunoreactivity of forebrain neurons in senescence-accelerated mice. One group of accelerated senescence-prone mice (accelerated senescence-prone-8) received [Ala16] acidic fibroblast growth factor (1-29), whereas the other group of accelerated senescence-prone-8 mice and a group of accelerated senescence-resistant mice (control) received vehicle solution. Injections began at three weeks after birth and were given weekly for 10 months. In a passive avoidance test, the mean retention latency at three, six and nine months of age was significantly longer in controls (vehicle-treated accelerated senescence-resistant-1) and acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 than in vehicle-treated accelerated senescence-prone-8 mice, and the latency in acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 mice was significantly shorter than that in controls only at nine months of age. In the Morris water maze task, the mean latency to climb onto the platform was significantly longer in acidic fibroblast growth factor fragment- and vehicle-treated accelerated senescence-prone-8 mice than in controls. However, the mean latency in the third and fourth trial blocks was significantly shorter for acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 than for vehicle-treated accelerated senescence-prone-8 mice. In the probe trials, controls and acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 mice spent significantly more time in the quadrant in which the platform had previously been located than in the other three quadrants. In acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 mice, the density of medial septum neurons intensely stained for choline acetyltransferase was significantly greater than that in vehicle-treated accelerated senescence-prone-8 mice, but significantly less than that in controls. The results indicate that the beneficial effect of [Ala16] acidic fibroblast growth factor (1-29) on learning and memory function in accelerated senescence-prone-8 mice may be related to a preservation of function in medial septum cholinergic neurons.

Aging↗

PubMed1999

Distribution of fibroblast growth factor-5 in rat hypothalamus, and its possible role as a regulator of feeding behaviour.

We previously reported that a transcript of fibroblast growth factor-5 (FGF-5) was more abundant in the brain of postnatal and adult mice than in the embryonic brain. This suggested that FGF-5 plays some role in the mature brain. Here, we have investigated the spatiotemporal expression and function of FGF-5 in the adult rat hypothalamus with the emphasis on feeding behaviour. In situ hybridization experiments demonstrated that, in both adequately fed and fasted (20 h) rats, FGF-5 transcripts were present within several nuclei in the hypothalamus (viz. the magnocellular part of the paraventricular nucleus, supraoptic nucleus, arcuate nucleus, median eminence, and ventromedial hypothalamic nucleus), but not in the lateral hypothalamic area. Quantitative detection of FGF-5 mRNA in the hypothalamus (especially in the paraventricular nucleus) indicated that food deprivation (20 h) reduced the expression of this gene to almost one-half of that seen in the control (fed) rats. The expression recovered to the control level after 1 h re-feeding, and this recovery persisted for several hours. Furthermore, FGF-5, when infused into the third ventricle, consistently reduced food intake, water intake and body weight gain, all in a dose-dependent manner. These results suggest that FGF-5 in the hypothalamus acts as a physiological regulator of feeding behaviour, and that its decreased expression during food deprivation may be important in stimulating appetite.

Animals↗

PubMed1998

An alternatively spliced fibroblast growth factor (FGF)-5 mRNA is abundant in brain and translates into a partial agonist/antagonist for FGF-5 neurotrophic activity.

We detected in the brain and then cloned two novel, short forms of human and mouse fibroblast growth factor (FGF)-5 mRNA, which were designated human FGF-5S (hFGF-5S) and mouse FGF-5S (mFGF-5S), respectively. Genomic analysis indicated that mFGF-5S and authentic mFGF-5 mRNAs were transcribed from a single gene; hFGF-5S and mFGF-5S mRNAs were generated by excluding the second exon of the respective FGF-5 genes, and the alternatively spliced mRNAs encoded for 123- and 121-amino acid proteins, respectively. Indeed, a neuron-like cell line expressing mFGF-5S mRNA secreted a protein of the expected size and with FGF-5 antigenicity. In PC12 cells, expression of hFGF-5 or exposure to hFGF-5 protein induced differentiation. Neither expression of hFGF-5S, alone, nor co-expression of hFGF-5S with hFGF-5 induced significant differentiation. At high concentrations, hFGF-5S protein partially antagonized FGF-5 activity, whereas by itself, hFGF-5S exerted very weak neurotrophic activity. hFGF-5S protein binds to FGF receptor (FGFR)-1 on PC12 transfectants and partially inhibits hFGF-5-induced tyrosine phosphorylation of FGFR-1 and an FGFR substrate, but it also induces phosphorylation by itself. These results suggest that FGF-5S is a naturally expressed partial agonist/antagonist of FGF-5 neurotrophic activity in the brain and that its effects are exerted in part at the level of the receptor.

Alternative Splicing↗

PubMed1998

Strong suppression of feeding by a peptide containing both the nuclear localization sequence of fibroblast growth factor-1 and a cell membrane-permeable sequence.

Earlier studies have shown that fibroblast growth factor (FGF)-1 in the brain regulates feeding behavior. In the present study, food intake in rats was strongly suppressed by an infusion into the lateral cerebroventricle of a synthetic peptide (26 amino acids) which contains both the N-terminal nuclear localization sequence (NLS) of FGF-1 and a recently identified membrane-permeable sequence. When the NLS motif in the peptide was destroyed by mutations of two lysine residues, the mutant peptide failed to affect eating. The results suggest that the NLS of FGF-1 plays an important role in FGF-1-induced feeding suppression and they introduce a novel compound for feeding regulation.

Amino Acid Sequence↗

PubMed1998

A set of van der Waals and coulombic radii of protein atoms for molecular and solvent-accessible surface calculation, packing evaluation, and docking.

We analyze the contact distance distributions between nonbonded atoms in known protein structures. A complete set of van der Waals (VDW) radii for 24 protein atom types and for crystal-bound water is derived from the contact distance distributions of these atoms with a selected group of apolar atoms. In addition, a set of Coulombic radii for polar atoms is derived from their contacts with water. The contact distance distributions and the two sets of radii are derived in a systematic and self-consistent manner using an iterative procedure. The Coulombic radii for polar atoms are, on average, 0.18 A smaller than their VDW radii. The VDW radius of water is 1.7 A, which is 0.3 A larger than its Coulombic radius. We show that both the VDW and the Coulombic radii of polar atoms are needed in calculating the molecular and solvent-accessible surfaces of proteins. The VDW radii are needed to generate the apolar portions of the surface and the Coulombic radii for the polar portions. The fact that polar atoms have two apparent sizes implies that a hydrophobic cavity has to be larger than a polar cavity in order to accommodate the same number of water molecules. Most surface area calculations have used only one radius for each polar atom. As a result, unreal cavities, grooves, or pockets may be generated if the Coulombic radii of polar atoms are used. On the other hand, if the VDW radii of polar atoms are used, the details of the polar regions of the surface may be lost. The accuracy of the molecular and the solvent-accessible surfaces of proteins can be improved if the radii of polar atoms are allowed to change depending on the nature of their contacting neighbors. The surface of a protein at a protein-protein interface differs from that in solution in that it has to be generated using at least two kinds of probes, one representing a typical apolar atom and the other a typical polar atom. This observation has important implications for docking, which relies on surface complementarity at the interface.

Evaluation Studies as Topic↗

PubMed1998

A single pre-training glucose injection induces memory facilitation in rodents performing various tasks: contribution of acidic fibroblast growth factor.

Effects of a pre-training intraperitoneal glucose injection on learning and memory were tested using two tasks: passive avoidance and Morris water maze. In the former task, mice that had received glucose 2 h prior (but not 1, 3, or 5 h prior) to a trial that combined acquisition with passive avoidance of foot shock showed a significantly increased retention latency when tested 24 h later. Thus, this effect was time-dependent, and it was also found to be dose-dependent by further experiment. In contrast, 2-deoxy-D-glucose and fructose had no such effect. In the Morris water maze task, glucose injection 2 or 3 h before a block of trials enhanced the spatial memory performance of mice. These glucose-induced memory-facilitation effects were abolished by an intracerebroventricular injection of anti-acidic fibroblast growth factor antibody 30 min before the glucose injection, suggesting a critical role for endogenous acidic fibroblast growth factor in this facilitatory effect. Furthermore, continuous intracerebroventricular infusion of acidic fibroblast growth factor in rats significantly increased retention latency (when tested repeatedly on successive days using a passive avoidance task). Our earlier studies demonstrated that brain acidic fibroblast growth factor is produced in the ependymal cells of the cerebroventricular system, and is released into the cerebrospinal fluid following either a meal or a (intraperitoneal or intracerebroventricular) glucose injection. This released acidic fibroblast growth factor also diffuses into the brain parenchyma, and is taken up by neurons in the hippocampus, hypothalamus, and elsewhere in the brain some 2 h after the meal or glucose injection. These and the present findings indicate (i) that pre-training glucose injection improves memory performance, and (ii) that acidic fibroblast growth factor, especially by its action within the hippocampus, is involved in this enhancement process.

Animals↗

PubMed1997

Interleukin-6 inhibits long-term potentiation in rat hippocampal slices.

The effects of recombinant human interleukin-6 (rhIL-6) on long-term potentiation (LTP) induced in the Schaffer collateral/commissural-CA1 pathway were examined using rat hippocampal slices. Field excitatory postsynaptic potential was recorded in the stratum radiatum of the CA1 region. Ten-min applications of rhIL-6 (50-2000 U/ml), started 5 min before the tetanus, significantly inhibited the induction of LTP, and in high doses of rhIL-6 also inhibited short-term potentiation (over 200 U/ml) and post-tetanic potentiation (over 500 U/ml). The effects of rhIL-6 (500 U/ml) were completely abolished by the preincubation of the slices with monoclonal anti-IL-6 receptor antibody (16 microg/ml) for 2 h. Heat-inactivated rhIL-6 had no effect on the synaptic potentiation. RhIL-6 affected neither the previously established LTP nor the basal synaptic transmission. These findings indicated that rhIL-6 modulated synaptic potentiation through the IL-6 receptor-mediated process in the hippocampus, probably by affecting post- and presynaptic sites in the CA1 region. The possible mechanisms of the IL-6-induced suppression of the synaptic potentiation were discussed.

Action Potentials↗

PubMed1996

Fibroblast growth factor receptor-1 in the lateral hypothalamic area regulates food intake.

Previous studies have shown that acidic and basic fibroblast growth fa ctor (aFGF and bFGF) and certain fragments of the aFGF N-terminal suppress food intake in rats due to their inhibitory actions on the glucose-sensitive neurons in the lateral hypothalamic area (LHA). The present study was planned to determine the role of FGF receptor-1 (FGFR-1), which was found in the LHA neurons of rats, on feeding regulation. The structure-activity relationship of aFGF fragments in feeding suppression was also investigated. An injection of anti-FGFR-1 antibody (250 and 350 ng) into the bilateral LHA significantly increased food intake. Synthesized aFGF fragments were infused into the III ventricle to elucidate the structure-activity relationship on the inhibition of feeding. Although aFGF-(1-29) did not affect food intake, [Ser16]aFGF-(1-29) (400 ng) and [Glu16]aFGF-(1-29) (400 NG), in which the cysteine residue at position 16 of aFGF(1-29) was replaced with structurally similar serine and glutamic acid, were observed to significantly inhibit food intake. These findings suggest that endogenous FGFR-1 in the LHA plays an important role in FGF-induced feeding suppression, while, in addition, the dissolving disulfide bond formation in aFGF fragments enhances their inhibitory effects on feeding.

Amino Acid Sequence↗

PubMed1995

Actions of acidic fibroblast growth factor fragments on food intake in rats.

Acidic fibroblast growth factor (aFGF) has suppressive effects on food intake. In the present study, the effect of aFGF fragments on food intake were investigated in rats. Infusion of a carboxyl-terminal fragment of aFGF, aFGF-(114-140), did not affect food intake, whereas an amino-terminal fragment of aFGF, aFGF-(1-15), was significantly inhibitory. Other amino-terminal fragments, aFGF-(1-20), aFGF-(1-29) and aFGF-(9-29), did not affect food intake. However, [Ala16]aFGF-(1-29) and [Ser16]aFGF-(1-29) in which the cysteine residue at position 16 was replaced with alanine and serine, respectively, had significant suppressive effects on food intake. Infusion of a functional antagonist for FGF receptor, anti-FGFR-1 antibody, into the lateral hypothalamus (LHA) significantly increased food intake. The results suggest that: the amino-terminal portion of aFGF is active in food intake suppression; the replacement of cysteine residue by alanine or serine is important in some amino-terminal aFGF fragments; and the LHA is involved in feeding suppression actions by aFGF and some fragments.

Alanine↗

PubMed1994

Effects of fibroblast growth factors and related peptides on food intake by rats.

The effects of acidic fibroblast growth factor (aFGF), basic FGF (bFGF), and related peptides, such as aFGF fragments, on food and water intake were investigated. Infusion of aFGF and bFGF into the third cerebral ventricle significantly suppressed food intake. The potency of aFGF was 1.5 that of bFGF in food intake inhibition. Both FGFs also suppressed water intake. Infusion of a carboxyl-terminal fragment of aFGF, aFGF-(114-140), did not affect food intake, whereas an amino-terminal fragment of aFGF, aFGF-(1-15), was significantly inhibitory. Other amino-terminal fragments, aFGF-(1-20) and aFGF-(1-29), did not affect food intake. However, [Ala16]aFGF-(1-29), in which the cysteine residue at position 16 was replaced with alanine, significantly suppressed food intake. Infusions of functional antagonists for FGFs, anti-aFGF, anti-bFGF, and anti-aFGF-(1-15) IgGs, into the lateral hypothalamus significantly increased food intake. The results suggest that: aFGF, bFGF, and some amino-terminal peptides of aFGF participate in the central regulation of food intake; the lateral hypothalamus is involved in their feeding suppression actions; and these peptides may function as physiologically relevant substances in the adult central nervous system, other than as neurotrophic factors.

Animals↗

PubMed1994

[Intracerebroventricular infusions of fibroblast growth factor and its fragments suppress nocturnal feeding in rats].

Acidic fibroblast growth factor1-140 (aFGF1-140), basic FGF1-146 (bFGF1-146) and several aFGF fragments were injected into the 3rd ventricle of rats to investigate their acute effects on the nocturnal food intake. Infusions of aFGF1-140 and bFGF1-146 immediately before the onset of darkness significantly suppressed the food intake for 12 hrs in a dose-dependent manner. The potency of aFGF1-140 to inhibit the feeding was 1.5 times greater than that of bFGF1-146. While an infusion of aFGF114-140 (a C-terminal fragment) had no effect on the feeding, that of aFGF1-15 (a N-terminal fragment) suppressed the food intake, although its potency corresponded to about 1/80 of the same molar concentration of aFGF1-140. An infusion of the other aFGF fragments containing N-terminals (aFGF1-29, aFGF1-20) or aFGF9-29 had no effect on the food intake. However, [16Ala]aFGF1-29, in which the cysteine residue at the position 16 was replaced with alanine, significantly depressed the food intake. Its potency was about 1/20 that of aFGF1-140. These results suggest that aFGF1-140 and bFGF1-146 participate in the central regulation of food intake, and that the amino-terminal portion of aFGF is critical for its action on feeding regulation.

Animals↗