Jaw movement-related primary somatosensory cortical area in the rat.

It has anatomically been revealed that the rostral part of the rat primary somatosensory cortex (S1) directly projects to the dorsal part of the trigeminal oral subnucleus (dorVo) and the dorsal part of juxtatrigeminal region (dorVjuxt), and that the dorVo and dorVjuxt contain premotoneurons projecting directly to the jaw-opening or jaw-closing motoneurons in the trigeminal motor nucleus (Vmo). However, little is known about how the rostral S1 regulates jaw movements in relation to its corticofugal projections. To address this issue, we performed intracortical microstimulation of the rat rostral S1 by monitoring jaw movements and electromyographic (EMG) activities. We for the first time found that low-frequency long-train stimulation of the rostral S1 induced single sustained opening of the jaw with elevated EMG activities of the anterior digastric muscles (jaw-opener). The effective sites for the low-frequency long-train stimulation overlapped the S1 sites where traditional high-frequency short-train stimulation was effective to induce single twitch-like jaw movement. We also found that the effective sites for the two kinds of train stimuli were included in the rostral S1 area, which has previously been identified to send direct projections to the dorVo or the dorVjuxt. Specifically, the most effective stimulation sites for the two kinds of train stimuli were located in the rostralmost part of S1 which has been reported to emanate strong direct projections to the dorVjuxt but less to the dorVo. Therefore, the present study suggests that the rat rostral S1, especially its rostralmost part, plays an important role in controlling jaw movements by activation of direct descending projections from the rostral S1 to the trigeminal premotoneuron pools, especially to the dorVjuxt.

Somatotopic direct projections from orofacial areas of secondary somatosensory cortex to trigeminal sensory nuclear complex in rats.

Little is known about the projections from the orofacial areas of the secondary somatosensory cortex (S2) to the pons and medulla including the second-order somatosensory neuron pools. To address this in rats, we first examined the distribution of S2 neurons projecting to the trigeminal principal nucleus (Vp) or oral subnucleus (Vo) of the trigeminal sensory nuclear complex (TSNC) after injections of a retrograde tracer, Fluorogold (FG), into five regions in the Vp/Vo which were responsive to stimulation of trigeminal nerves innervating the orofacial tissues. A large number of FG-labeled neurons were found with a somatotopic arrangement in the dorsal areas of S2 (orofacial S2 area). This somatotopic arrangement in the orofacial S2 area was shown to closely match that of the orofacial afferent inputs by recording cortical surface potentials evoked by stimulation of the trigeminal nerves. We then examined the morphology of descending projections from these electrophysiologically defined areas of the orofacial S2 to the pons and medulla after injections of an anterograde tracer, biotinylated dextranamine (BDA), into the areas. A large number of BDA-labeled axon fibers and terminals were seen only in some of the second-order somatosensory neuron pools, most notably in the contralateral TSNC, although the labeled terminals were not seen in certain rostrocaudal levels of the contralateral TSNC including the rostrocaudal middle level of the trigeminal interpolar subnucleus. The projections to the TSNC showed somatotopic arrangements in dorsoventral, superficial-deep and rostrocaudal directions. The somatotopic arrangements in the Vp/Vo closely matched those of the electrophysiologically defined central projection sites of the orofacial trigeminal afferents in the TSNC. The present results suggest that the orofacial S2 projects selectively to certain rostrocaudal levels of the contralateral TSNC, and the projections may allow the orofacial S2 to accurately modulate orofacial somatosensory transmission to higher brain centers including the orofacial S2 itself.

Corticofugal direct projections to primary afferent neurons in the trigeminal mesencephalic nucleus of rats.

Little is known about projections from the cerebral cortex to the trigeminal mesencephalic nucleus (Vmes) which contains the cell bodies of primary sensory afferents innervating masticatory muscle spindles and periodontal ligaments of the teeth. To address this issue, we employed retrograde (Fluorogold, FG) and anterograde (biotinylated dextranamine, BDA) tracing techniques in the rat. After injections of FG into the Vmes, a large number of neurons were retrogradely labeled in the prefrontal cortex including the medial agranular cortex, anterior cingulate cortex, prelimbic cortex, infralimbic cortex, deep peduncular cortex and insular cortex; the labeling was bilateral, but with an ipsilateral predominance to the injection site. Almost no FG-labeled neurons were found in the somatic sensorimotor cortex. After BDA injections into the prefrontal cortex, anterogradely labeled axon fibers and boutons were distributed bilaterally in a topographic pattern within the Vmes, but with an ipsilateral predominance to the injection site. The rostral Vmes received more preferential projections from the medial agranular cortex, while the deep peduncular cortex and insular cortex projected more preferentially to the caudal Vmes. Several BDA-labeled axonal boutons made close associations (possible synaptic contacts) with the cell bodies of Vmes neurons. The present results have revealed the direct projections from the prefrontal cortex to the primary sensory neurons in the Vmes and their unique features, suggesting that deep sensory inputs conveyed by the Vmes neurons from masticatory muscle spindles and periodontal ligaments are regulated with specific biological significance in terms of the descending control by the cerebral cortex.

GABA- and glycine-like immunoreactivity in axonal endings presynaptic to the vibrissa afferents in the cat trigeminal interpolar nucleus.

The goal of this study was to analyze the synaptic interaction of primary afferents with GABA- and/or glycine-immunopositive presynaptic endings in the cat trigeminal interpolar nucleus (Vi). Fast adapting vibrissa afferents were labeled by intra-axonal injections of horseradish peroxidase. Postembedding immunogold labeling on serially cut ultrathin sections and quantitative ultrastructural analysis of the labeled boutons and their presynaptic endings (p-endings) in the Vi were performed. The majority of p-endings presynaptic to labeled boutons (83%) were immunopositive for both GABA and glycine and 8% were immunopositive for glycine alone. A small fraction of p-endings were immunopositive for GABA alone (4%) or immunonegative for both GABA and glycine (4%). Ultrastructural parameters related to synaptic release, i.e. bouton volume, mitochondrial volume, and active zone area, were significantly larger in the labeled boutons of primary afferents than in the p-endings. The volume of labeled boutons was positively correlated with the number of the postsynaptic dendrites and p-endings. In addition, fairly large-sized labeled boutons and p-endings were frequently observed in the Vi. These results reveal that large majority of vibrissa afferents in the Vi are presynaptically modulated by interneurons immunopositive for both GABA and glycine, and suggest that the Vi plays a distinct role in the processing of orofacial sensory information, different from that of other trigeminal sensory nuclei.

The association of genetic variants in Krüppel-like factor 11 and Type 2 diabetes in the Japanese population.

AIMS: Krüppel-like factor 11 (KLF11) is a transcriptional factor of the zinc finger domain family that regulates the expression of insulin. In North European populations, its common functional variant Q62R (rs35927125) is a strong genetic factor for Type 2 diabetes (P = 0.00033, odds ratio for G allele = 1.29, 95% CI 1.12-1.49). We examined the contribution of KLF11 variants to the susceptibility to Type 2 diabetes in a Japanese population. METHODS: By re-sequencing Japanese individuals (n = 24, partly 96), we screened all four exons, exon/intron boundaries and flanking regions of KLF11. Verified single nucleotide polymorphisms (SNPs) were genotyped in 731 initial samples (369 control and 362 case subjects). Subsequently, we tested for association in 1087 samples (524 control and 563 case subjects), which were collected in different districts of Japan from the initial samples. RESULTS: We identified eight variants, including a novel A/C variant on intron 3, but no mis-sense mutations. In an association study, we failed to find any significant result of SNPs (minor allele frequency 8.2-46.2%) after correcting for multiple testing. Similarly, no haplotypes were associated with Type 2 diabetes. It is notable that the G allele in rs35927125 was completely absent in 1818 Japanese individuals. CONCLUSIONS: Genetic variants in KLF11 are unlikely to have a major effect of Type 2 diabetes in the Japanese population, although they were significantly associated in North European populations. These observations might help to determine the role of KLF11 variants in Type 2 diabetes in different populations.

Genetic association of single nucleotide polymorphisms in endonuclease G-like 1 gene with type 2 diabetes in a Japanese population.

AIMS/HYPOTHESIS: In order to identify type 2 diabetes disease susceptibility gene(s) in a Japanese population, we applied a region-wide case-control association test to the 20.4 Mb region between D3S1293 and D3S2319 on chromosome 3p24.3-22.1, supported by linkage to type 2 diabetes and its related traits in Japanese and multiple populations. MATERIALS AND METHODS: We performed a two-stage association test using 1,762 Japanese persons with 485 gene-centric, evenly spaced, common single nucleotide polymorphism (SNP) markers with minor allele frequency >0.1. For mouse studies, total RNA was extracted from various organs of BKS.Cg-+Lepr(db)/+Lepr(db) and control mice, and from MIN6, NIH3T3 and C2C12 cell lines. RESULTS: We detected a landmark SNP375 (A/G) (rs2051211, p = 0.000046, odds ratio = 1.33, 95% CI 1.16-1.53) in intron 5 of the endonuclease G-like 1 (ENDOGL1) gene. Systematic dense SNPs approach identified a susceptibility linkage disequilibrium (LD) block of 116.5 kb by |D'|, an LD units map and a critical region of 2.1 kb by r (2) in ENDOGL1. A haplotype-based association test showed that an at-risk haplotype is associated with disease status (p = 0.00001). The expression of ENDOGL1 was rather ubiquitous with relatively abundant expression in the brain and also in a pancreatic islet beta cell line. Mouse Endogl1 expression increased in pancreatic islets of hyperglycaemic BKS.Cg-+Lepr(db)/+Lepr(db) mice compared with that in control mice. CONCLUSIONS/INTERPRETATION: Based on the population genetics, fine mapping of LD block and haplotype analysis, we conclude that ENDOGL1 is a candidate disease-susceptibility gene for type 2 diabetes in a Japanese population. Further analysis in a larger sample size is required to substantiate this conclusion.

Elimination of neurokinin-1 receptor neurons in caudal nucleus reverses the effects of systemic bicuculline on c-Fos expression in rat trigeminal sensory nucleus: I. High intensity electrical stimulation of the trigeminal ganglion.

Although neurokinin-1 receptor (NK-1)-bearing neurons are distributed in lamina I of the trigeminal caudal nucleus (Vc) and constitute major projection neurons, little is known about their fundamental role(s) in nociceptive processing. This study examines the effect of intra cisterna magna injection of substance P (SP) conjugated to saporin (SP-Sap; 5 microM, 5 microl) [with/without systemic administration of bicuculline] on c-Fos expression in the trigeminal sensory nucleus (TSN) induced 2 h after 10 min repetitive electrical stimulation of the trigeminal ganglion (TG) at high intensity (1.0 mA, 5 Hz, 5 ms) in the urethane-anesthetized rat. In the SP-Sap-treated rats, the numbers of NK-1-immunopositive neurons in laminae I and III of the Vc decreased compared with rats similarly pretreated with saline (Sal; 5 microl) or blank-saporin (Bl-Sap; 5 microM, 5 microl). In Sal- or Bl-Sap-treated controls, high intensity stimulation induced c-Fos expression in neurons throughout the full extent of ipsilateral superficial layers of the Vc (VcI/II), magnocellular zone of the Vc (VcIII/IV) and the dorsal or dorsomedial subdivisions of the rostral TSN above the obex (trigeminal principal, oral (Vo) and interpolar nuclei). Preadministration of bicuculline (2 mg/kg, i.p.) decreased the numbers of c-Fos-immunopositive neurons in the VcI/II, VcIII/IV and Vo in Sal- or Bl-Sap-treated controls. In contrast, high intensity stimulation induced less c-Fos-immunopositive neurons in the VcI/II and Vo of rats treated with SP-Sap compared with those in Sal- or Bl-Sap-treated controls. In SP-Sap-treated rats preadministered with bicuculline, the numbers of c-Fos-immunopositive neurons in the VcI/II and Vo were increased compared with the SP-Sap-treated rats preadministered with Sal. These results suggest that NK-1-immunopositive neurons in laminae I and III of Vc play a pivotal role in the nociceptive specific processing in the TSN through GABA(A) receptors.

The distribution of inhibitory and excitatory synapses on single, reconstructed jaw-opening motoneurons in the cat.

In a previous study, we reported that the distribution of inhibitory input, in contrast to excitatory input, decreased somatofugally along dendrites of cat jaw-closing alpha-motoneurons [J Comp Neurol 414 (1999) 454]. The present study examined the distribution of GABA, glycine, and glutamate immunopositive boutons covering horseradish peroxidase-labeled cat jaw-opening motoneurons. The motoneurons were divided into four compartments: the soma, and primary, intermediate, and distal dendrites. Ninety-seven percent of the total number of studied boutons had immunoreactivity for at least one of the three amino acids. The proportion of boutons immunoreactive for GABA and/or glycine was lower than the proportion of boutons immunoreactive for glutamate. Boutons immunoreactive to glycine alone were more numerous than boutons double-labeled for GABA and glycine, which, in turn, occurred more frequently than boutons immunoreactive to GABA alone. The percentage synaptic covering (proportion of membrane covered by synaptic boutons) of the putatively excitatory (glutamate containing) and putatively inhibitory (GABA and/or glycine containing) boutons decreased somatofugally along the dendrites. Such systematic variations were not seen in the packing density (number of boutons per 100 microm(2)); the packing density showed a distinct drop between the soma and primary dendrites but did not differ significantly among the three dendritic compartments. Overall, the packing density was slightly higher for the putatively excitatory boutons than for the inhibitory ones. When taken together with previous analyses of jaw-closing alpha-motoneurons the present data on jaw-opening alpha-motoneurons indicate that the two types of neuron differ in regard to the nature of synaptic integration in the dendritic tree.

Redox state-dependent and sorbitol accumulation-independent diabetic albuminuria in mice with transgene-derived human aldose reductase and sorbitol dehydrogenase deficiency.

AIMS/HYPOTHESIS: We investigated the role played by sorbitol accumulation in the kidney in the development of diabetic albuminuria. METHODS: We created mice ( hAR-Tg:SDH null) with transgene-derived human aldose reductase and sorbitol dehydrogenase (SDH) deficiency, and analysed (i). the contribution of accumulated sorbitol to urinary albumin excretion rate, and (ii). the effect of the aldose reductase inhibitor, epalrestat, on the diabetic redox state, including decreased renal reduced glutathione concentrations or increased lactate to pyruvate ratios in the diabetic kidney. RESULTS: Compared to littermates, non-diabetic transgenic mice had a 2.6-fold increase in aldose reductase mRNA. In a diabetic group, aldose reductase mRNA in hAR-Tg mice was 2.7-fold higher than in littermates. In the diabetic and non-diabetic groups, hAR-Tg:SDH null mice had the highest sorbitol content among all four genetic types including hAR-Tg:SDH null, SDH null, hAR-Tg and littermates. The urinary albumin excretion rate in non-diabetic groups was similar in the four genetic types of mouse. In diabetic groups it was greater than in non-diabetic groups, but did not correlate with the sorbitol content among the four genetic types of mouse. When aldose reductase inhibitor and streptozotocin were given simultaneously at 6 weeks of age, epalrestat prevented diabetic increases in urinary albumin excretion rate and completely prevented diabetic decreases in reduced glutathione concentrations and diabetic increases in lactate to pyruvate ratios, even in the presence of transgenic aldose reductase. CONCLUSIONS/INTERPRETATION: The degree of diabetic albuminuria in genetically modified mice is dependent on the redox state and independent of polyol accumulation; aldose reductase inhibitor can prevent diabetic albuminuria by normalising diabetic redox changes.

An involvement of trigeminal mesencephalic neurons in regulation of occlusal vertical dimension in the guinea pig.

Although the occlusal vertical dimension (OVD) is strictly controlled, the neuronal mechanism of its regulation is still unclear. We hypothesize that neurons in the trigeminal mesencephalic nucleus (MesV) play an important role in the regulation of the OVD, because the MesV receives the projection from jaw-closing muscle spindles and periodontal mechanoreceptors. We measured the temporal OVD change in the guinea pig to study the effects of MesV lesions on the OVD. OVD-raised animals without MesV lesions showed a rapid OVD decrease to the same level as that in naïve controls, followed by an OVD increase after the OVD-raising appliance was removed. In contrast, OVD-raised animals with MesV lesions showed only a slight decrease in the OVD for 15 days after removal of the appliance, and then the OVD increased. The time-course of OVD development in normal-bite animals with MesV lesions was similar to that of naïve controls. These results suggest that MesV neurons are involved in OVD regulation.

Jaw-muscle spindle afferent pathways to the trigeminal motor nucleus in the rat.

Neural pathways conveying proprioceptive feedback from the jaw muscles were studied in rats by combining retrograde and intracellular neuronal labeling. Initially, horseradish peroxidase was iontophoresed unilaterally into the trigeminal motor nucleus (Vmo). Two days later, 1-5 jaw-muscle spindle afferent axons located in the mesencephalic trigeminal nucleus were physiologically identified and intracellularly stained with biotinamide. Stained mesencephalic trigeminal jaw-muscle spindle afferent axon collaterals and boutons were predominantly distributed in the supratrigeminal region (Vsup), Vmo, dorsomedial trigeminal principal sensory nucleus (Vpdm), parvicellular reticular formation (PCRt), alpha division of the parvicellular reticular formation (PCRtA), and dorsomedial portions of the spinal trigeminal subnuclei oralis (Vodm), and interpolaris (Vidm). Numerous neurons retrogradely labeled with horseradish peroxidase from the trigeminal motor nucleus were found bilaterally in the PCRt, PCRtA, Vodm, and Vidm. Retrogradely labeled neurons were also present contralaterally in the Vsup, Vpdm, Vmo, peritrigeminal zone, and bilaterally in the dorsal medullary reticular field. Putative contacts between intracellularly stained mesencephalic trigeminal jaw-muscle spindle afferent boutons and trigeminal premotor neurons retrogradely labeled with horseradish peroxidase were found in the ipsilateral Vodm, PCRtA, and PCRt, as well as the contralateral Vsup, Vmo, Vodm, PCRt, and PCRtA. Thus, multiple disynaptic jaw-muscle spindle afferent-motoneuron circuits exist. These pathways are likely to convey long-latency jaw-muscle stretch reflexes and may contribute to stiffness regulation of the masticatory muscles.

Quantitative ultrastructure of slowly adapting lingual afferent terminals in the principal and oral nuclei in the cat.

Previous studies provide evidence that a structure/function correlation exists in the cytoarchitectonically different zones of the trigeminal sensory nuclei. To extend this relationship, we examined the ultrastructural features of trigeminal primary afferent neurons in the cat dorsal principal nucleus (Vpd) and the rostrodorsomedial oral nucleus (Vo.r) using intra-axonal labeling with horseradish peroxidase and morphometric analyses. All labeled boutons contained round synaptic vesicles. Eighty-two percent of the boutons in the Vo.r and 99% of the boutons in the Vpd were presynaptic to nonprimary dendrites. The remaining boutons in the Vo.r were presynaptic to somata (8%) or primary dendrites (10%). The average number of postsynaptic profiles per labeled bouton did not differ in the Vpd and Vo.r. Most labeled boutons in the two nuclei were postsynaptic to unlabeled axon terminals with pleomorphic vesicles (p-ending). The number of p-endings per labeled bouton was higher in the Vpd than Vo.r A morphometric analysis indicated that labeled bouton volume and apposed surface area were larger in the Vpd than Vo.r while active zone area and vesicle number did not differ. All these parameters were larger than those of p-endings in each nucleus. In both labeled boutons and p-endings, the parameters were positively correlated with bouton size. These results suggest that sensory information conveyed through trigeminal afferents is more strongly controlled at the level of the first synapse by presynaptic mechanisms in the Vpd than in the Vo.r, while the efficacy of transmission at primary afferent synapses does not differ.

Quantitative ultrastructure of synapses on functionally identified primary afferent neurons in the cat trigeminal mesencephalic nucleus.

Though a number of studies have reported the presence of synapses on neurons in the trigeminal mesencephalic nucleus (Vmes), there have been no quantitative studies of either the density of innervation, or the ultrastructure, of the synapses on single, physiologically identified neurons in this nucleus. In this study we recorded from single neurons in the Vmes, identified them as being either muscle spindle afferents (MS) or periodontal ligament mechanoreceptor afferents (PL), and then labeled the neurons by intra-axonal injection of horseradish peroxidase (HRP). The material was first processed to reveal the HRP activity, following which ultrathin sections through the labeled somata were cut and examined under the electron microscope. Complete serial reconstructions were made through the soma of one MS neuron and one PL neuron, and the contacts on the neurons reconstructed. Boutons were found on the soma, spines, appendages and the axon hillock and the initial segment of the axon. The numbers of boutons terminating on the two neurons were 198 (PL) and 424 (MS), giving a packing density of 4.4 and 10.7 boutons respectively (i.e., number of boutons/100 micron 2 of the postsynaptic membrane). Boutons could be separated into two types on the basis of their vesicles: those containing clear, round vesicles (i.e., S-type) and those containing a mixture of round, oval and flattened vesicles (P-type). Ninety-five (PL neuron) and 99% (MS neuron) of terminals on the two neurons were P-type. All the S-type boutons and 80% of the P-type boutons formed asymmetric synaptic contacts while 10% of the P-type boutons made symmetric contacts. Quantitative measurements of the P-type boutons on the labeled neurons, in which the data of MS and PL neurons were pooled, revealed that bouton volume was highly correlated with bouton surface area, active zone number, total active zone area, vesicle number, and mitochondrial volume. However, comparing the quantitative measurements of the P-type boutons with those of previously reported vibrissa afferent terminals and their associated axon terminals revealed that all the parameters were smaller for the P-type boutons (on Vmes neurons) than those of the vibrissa afferent terminals but similar to those of axon terminals presynaptic to the vibrissa afferents. Taken together, our results emphasize the wide scope for synaptic interactions in the Vmes and suggest that it may be more fruitful to view the Vmes as an integrating center.

Feedback inhibition of amidophosphoribosyltransferase regulates the rate of cell growth via purine nucleotide, DNA, and protein syntheses.

To clarify the contributions of amidophosphoribosyltransferase (ATase) and its feedback regulation to the rates of purine de novo synthesis, DNA synthesis, protein synthesis, and cell growth, mutated human ATase (mhATase) resistant to feedback inhibition by purine ribonucleotides was engineered by site-directed mutagenesis and expressed in CHO ade (-)A cells (an ATase-deficient cell line of Chinese hamster ovary fibroblasts) and in transgenic mice (mhATase-Tg mice). In Chinese hamster ovary transfectants with mhATase, the following parameters were examined: ATase activity and its subunit structure, the metabolic rates of de novo and salvage pathways, DNA and protein synthesis rates, and the rate of cell growth. In mhATase-Tg mice, ATase activity in the liver and spleen, the metabolic rate of the de novo pathway in the liver, serum uric acid concentration, urinary excretion of purine derivatives, and T lymphocyte proliferation by phytohemagglutinin were examined. We concluded the following. 1) ATase and its feedback inhibition regulate not only the rate of purine de novo synthesis but also DNA and protein synthesis rates and the rate of cell growth in cultured fibroblasts. 2) Suppression of the de novo pathway by the salvage pathway is mainly due to the feedback inhibition of ATase by purine ribonucleotides produced via the salvage pathway, whereas the suppression of the salvage pathway by the de novo pathway is due to consumption of 5-phosphoribosyl 1-pyrophosphate by the de novo pathway. 3) The feedback inhibition of ATase is more important for the regulation of the de novo pathway than that of 5-phosphoribosyl 1-pyrophosphate synthetase. 4) ATase superactivity leads to hyperuricemia and an increased bromodeoxyuridine incorporation in T lymphocytes stimulated by phytohemagglutinin.

Co-infection by serologically-silent hepatitis B virus may contribute to poor interferon response in patients with chronic hepatitis C by down-regulation of type-I interferon receptor gene expression in the liver.

Intrahepatic mRNA levels of type-I interferon (IFN) receptor genes have been shown to correlate with the clinical efficacy of IFN therapy in patients with chronic hepatitis C. Recently, co-infection by serologically-silent hepatitis B virus (HBV) has been assumed to be associated with the poor IFN response in patients with chronic hepatitis C. The aim of this study was to investigate the relationship between the co-infection of serologically-silent HBV and type-I IFN receptor gene expression in the liver of patients with chronic hepatitis C. The intrahepatic mRNA levels of IFNAR2, one of the two subunits of the type-I IFN receptor, were quantified and compared with both the prevalence of HBV DNA and the hepatitis C virus (HCV) genotype in 45 patients with chronic hepatitis C, who were negative for hepatitis B surface antigen. Co-infection, as evaluated by a nested polymerase chain reaction, was present in 22 patients (48.9%), with dominance of the HCV genotype 1b (65.2%) over genotype 2a (31.8%). Co-infection was associated with lower IFNAR2 mRNA levels, higher levels of serum HCV RNA, and a poor IFN response, regardless of the HCV genotype. The findings suggest the possibility that co-infection by serologically-silent HBV is one of the factors that can lead to an unfavorable IFN response in chronic hepatitis C by down-regulation of IFN receptor gene expression in the liver.

[A case of AFP producing early gastric cancer successfully treated with small dose CDDP and 5-FU (PF) therapy].

A case of AFP producing early gastric cancer successfully treated with a small dose of CDDP and 5-FU therapy administered intermittedly is reported with a review of the literature. A 63-year-old male was admitted to our hospital because of liver metastasis with a high level of serum AFP (185.8 ng/ml) three months after gastrectomy. Systemic chemotherapy was performed twice with a regimen of CDDP 20 mg and 5-FU 750 mg/day in 5 days. After hepatic arterial infusion chemotherapy (HAIC) was performed once, the patient obtained partial response according to CT scan and was discharged. After he underwent HAIC once as an outpatient, liver metastasis completely disappeared 5 months after surgery. He was administered oral 5-FU, 150 mg and Krestin 3.0 g/day and underwent HAIC with CDDP 20 mg and 5-FU 750 mg/day every 2 weeks. After serum AFP level was returned to the normal range 7 months after surgery; HAIC was performed every 4 weeks and continued until one year after surgery. One year and 11 months after surgery, serum AFP remains within the normal limit and there is no evidence of recurrence.

Comparison of plastic prostheses and self-expandable metallic stents in the treatment of malignant esophageal stenosis.

OBJECTIVE: We compared the efficacy of plastic prostheses and self-expandable metallic stents in the treatment of malignant esophageal stenosis and/or fistula. SUBJECTS AND METHODS: Subjects were 31 patients with esophageal cancer, 4 with esophagotracheal fistula, and 1 with esophageal stenosis. A plastic prosthesis was inserted in 15 patients (group A) and a self-expandable metallic stent in 21 patients (group B). We evaluated food ingestion improvement, effectiveness, complications, mean survival, food ingestion duration, the percentage of food ingestion capability in total survival time, and inhospital mortality. RESULTS: No differences were seen in food intake improvement or in the effectiveness between groups, whereas fatal complications were higher in Group A. No significant differences were seen in mean survival, food ingestion duration, percentage of food ingestion capability, or inhospital mortality between groups. CONCLUSION: We concluded that a self-expandable metallic stent was safer than a plastic prosthesis because of fewer serious complications such as bleeding, and recommended the use of metallic stents in the treatment of malignant esophageal stenosis and/or fistula.