Neighbourhood relationships moderate the positive association between family caregiver burden and psychological distress in Japanese adults: a cross-sectional study.

OBJECTIVES: Family caregiver burden is associated with higher psychological distress. However, little is known about the impact of neighbourhood relationships on caregivers' psychological distress. We examined whether neighbourhood relationships of caregivers moderate the association between family caregiver burden and psychological distress. STUDY DESIGN: This was a cross-sectional study. METHODS: We recruited 5321 Japanese adults who participated in the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2013 and 2017. Participants completed self-reported questionnaires to measure psychological distress (Kessler 6: K6), subjective caregiver burden, and neighbourhood relationships. We performed a multivariable linear regression analysis in which caregiver burden was designated as an independent variable and the K6 score as a dependent variable, adjusting for demographics. The interaction term between caregiver burden and neighbourhood relationships was also included in the analysis. RESULTS: Data from a total of 5069 participants were included (mean age [standard deviation]: 63.1 years [10.3 years]; 2226 [43.9%] female). Caregiver burden was significantly and positively associated with psychological distress (compared with no burden, mild burden: ß = 0.24, P = 0.197; severe burden: ß = 0.60, P < 0.01; P for trend < 0.01). There was a significant negative interaction effect of caregiver burden × neighbourhood relationship on psychological distress (severe burden × good neighbourhood relationship: ß = -3.29, P < 0.01). CONCLUSIONS: A higher caregiver burden was associated with higher psychological distress, and neighbourhood relationships moderated this association. Our findings suggest that good neighbourhood relationships can buffer caregiving-associated psychological distress.

A combination of ultrasound-guided rectus sheath and transversus abdominis plane blocks is superior to either block alone for pain control after gynecological transumbilical single incision laparoscopic surgery.

PURPOSE: To investigate the efficacy of the combination of ultrasound-guided rectus sheath (RS) and transversus abdominis plane (TAP) blocks compared with TAP or RS block alone in gynecological single-incision laparoscopic surgery (SILS). MATERIALS AND METHODS: Bilateral TAP blocks (Group A, n = 12), TAP and RS blocks (Group B, n = 12), and RS blocks (Group C, n = 12) with 40 ml ropivacaine/patient were performed for ovarian tumor SILS. The analgesic effects were evaluated using a numerical rating scale (NRS) at zero, six, 12, 24, and 48 hours post-surgery. RESULTS: Umbilical pain on completion of general anesthesia was significantly less frequent in Group B (1/12) than Group A (7/12) (p = 0.03). The postoperative NRS scores were significantly lower in Group B than Group A at zero (p = 0.02) and six (p = 0.03) hours and Group C at zero (p = 0.001), six (p = 0.02), and 12 (p = 0.004) hours. CONCLUSION: The combination of RS and TAP blocks reduced early postoperative pain compared with RS or TAP block alone for gynecological SILS.

Effectiveness of ultrasound-guided transversus abdominis plane block and rectus sheath block in pain control and recovery after gynecological transumbilical single-incision laparoscopic surgery.

PURPOSE: To evaluate the effectiveness of ultrasound-guided transversus abdominis plane (TAP) and rectus sheath (RS) blocks in pain management and recovery after gynecological single-incision laparoscopic surgery (SILS). MATERIALS AND METHODS: Abilateral TAP block (Group A, n = 9), bilateral TAP and RS blocks (Group B, n = 10), and a bilateral RS block (Group C, n = 9) with 40 ml ropivacaine per patient were conducted in 28 patients undergoing SILS for ovarian tumors. A pain score and walking distance in a 6-minute walk test (6MWT) were examined. RESULTS: Pain scores were significantly lower on postoperative day (POD) 3 than on POD 1 in Groups B (p = 0.03) and C (p = 0.02). The walking distance on POD 3 was comparable with that before surgery in Group C (p = 0.75), but shorter in Groups A (p = 0.004) and B (p = 0.02). CONCLUSIONS: The RS block alone was the most effective in relieving pain and accelerating general recovery after gynecological SILS.

An analysis of the survival rate after radiotherapy in lung cancer patients with bone metastasis: is there an optimal subgroup to be treated with high-dose radiation therapy?

We investigated the prognostic factors after radiotherapy for bone metastasis from lung cancer while taking the recent findings in the treatment of such cases into consideration. A total of 132 patients with bone metastases from pathologically confirmed lung cancer were evaluated regarding the following potential prognostic factors: treatment for primary site (surgery vs. other), treatment site (spine vs. other), number of bone metastases (solitary vs. multiple), number of metastatic organs (0 vs. 1 vs. ≥2), neurological symptoms (no symptoms vs. numbness vs. paresis), degree of pain (no pain vs. mild pain vs. severe pain), performance status [PS] (0-1 vs. ≥2), biological effective dose [BED] (≥40 Gy vs. <40Gy), time to distant metastasis (≥1 year vs. <1 year), histology (adenocarcinoma vs. others), and use of epidermal growth factor receptor [EGFR]-targeted agents (Yes vs. No). The univariate analysis demonstrated that all factors except for the treatment site were significant. Surgery as treatment for primary site, solitary bone metastasis, no visceral organ metastasis, no symptoms or numbness, no pain, PS<2, BED≥40 Gy, time to distant metastasis ≥ 1year, adenocarcinoma histology, and use of EGFR-targeted agents were correlated with a favorable prognosis. In a multivariate analysis, solitary bone metastasis, PS<2, BED≥40 Gy, adenocarcinoma histology, and the use of EGFR-targeted agents were significantly correlated with a better survival (p = 0.038, 0.006, 0.003, 0.014, and <0.001, respectively). A contingency table to assess the relationship between each variable and the median survival time of the patients according to the administered BED showed that in patients with the time to distant metastasis ≥ 1year and the use of EGFR-targeted agents, the subgroups treated with BED≥40 Gy had a favorable prognosis. Our study suggests that high-dose radiotherapy is associated with a better prognosis in combination with other favorable prognostic factors.

Relationship of intake of plant-based foods with 6-n-propylthiouracil sensitivity and food neophobia in Japanese preschool children.

BACKGROUND/OBJECTIVES: Diets rich in plant-based foods such as vegetables, fruits and soy foods have been suggested to have beneficial effects on health. However, phytochemicals contained in plant-based foods are generally bitter and acrid. We investigated whether intake of vegetables, fruits and soy foods is associated with sensitivity to bitterness and reluctance to eat new foods (food neophobia) in Japanese preschool children. SUBJECTS/METHODS: Subjects of this cross-sectional study were healthy Japanese, 167 boys and 156 girls, aged 4-6 years. Intake of vegetables, fruits and soy foods was estimated from 3-day dietary records. Subjects were classified as either tasters or non-tasters of 6-n-propylthiouracil (PROP) based on their ability to taste 0.56 mmol/l PROP. Information on each child's age, height, weight, food neophobia status and food variety, as well as maternal diet and parental control over the child's eating, was obtained by a parent-administered questionnaire. Food neophobia was assessed using the Child Food Neophobia Scale (CFNS). RESULTS: A high intake of vegetables was significantly associated with a low CFNS score in boys after controlling for covariates (P=0.0008). Among the boys, soy food intake was significantly higher in PROP non-tasters than in tasters, except those with low CFNS scores (P=0.0019). High intake of soy foods was significantly associated with a low neophobia score in PROP tasters but not in non-tasters (P=0.0024). CONCLUSIONS: These data suggest that sensitivity to bitter taste and food neophobia may influence the consumption of vegetables and soy foods among Japanese preschool boys.

Axonal projections of single auditory neurons in the thalamic reticular nucleus: implications for tonotopy-related gating function and cross-modal modulation.

Tonotopically comparable subfields of the primary auditory area (AI) and nonprimary auditory areas (non-AI), i.e. posterodorsal area (PD) and ventral auditory area (VA), in the rat cortex have similar topographies in the projection to the ventral division of the medial geniculate nucleus (MGV), but reverse topographies in the projection to the thalamic reticular nucleus (TRN). In this study, we examined axonal projections of single auditory TRN cells, using juxtacellular recording and labeling techniques, to determine features of TRN projections and estimate how the TRN mediates corticofugal inhibition along with the reverse topographies of cortical projections to the TRN. Auditory TRN cells sent topographic projections to limited parts of the MGV in a manner that relays cortical inputs from tonotopically comparable subfields of the AI and non-AI (PD and VA) to different parts of the MGV. The results suggest that corticofugal excitations from the AI and non-AI modulate thalamic cell activity in the same part of the MGV, whereas corticofugal inhibitions via the TRN modulate cell activity in different parts of the MGV with regard to tonotopic organization. The AI and non-AI could serve distinctive gating functions for auditory attention through the differential topography of inhibitory modulation. In addition, we obtained an intriguing finding that a subset of auditory TRN cells projected to the somatosensory but not to the auditory thalamic nuclei. There was also a cell projecting to the MGV and somatosensory nuclei. These findings extend the previously suggested possibility that TRN has a cross-modal as well as an intramodal gating function in the thalamus.

Activation of central 5HT2A receptors reduces the craniofacial nociception of rats.

We assessed the contribution of central 5HT2A receptors to the craniofacial tissue nociception in naïve male rats. First, we tested whether activation of central 5HT2A receptors affected nociceptive neural activities recorded from superficial laminae of the trigeminal subnucleus caudalis (Vc)/upper cervical spinal cord junction (Vc/C2) region. Two types of units, such as deep-nociceptive or skin-wide dynamic range (WDR) units were identified from extracellular recordings. Topical administration of 5HT2A receptor agonist, (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) onto the Vc/C2 region significantly reduced deep-nociceptive unit discharges evoked by formalin injection into the masseter muscle. Noxious pinch stimulation to the facial skin-evoked skin-WDR unit discharges was significantly reduced by topical administration of 0.1 mg/rat DOI onto the Vc/C2 region. Second, we tested whether i.c.v. administration of DOI affected Fos-like immunoreactivity (-LI) evoked by formalin injection into the masseter muscle. Fos-LI was significantly induced mainly at the ventrolateral (vl) area of trigeminal subnucleus interpolaris (Vi)/Vc junction (vl-Vi/Vc) region and Vc/C2 region in vehicle-treated rats. Formalin-evoked Fos-LI was significantly reduced in laminae I-II of the Vc/C2, but not vl-Vi/Vc region after i.c.v. administration of DOI. Finally, orofacial nocifensive behavioral activities evoked by formalin injection into the masseter muscle were significantly reduced by intracisternal administration of DOI. These results suggest that 5HT2A receptors in the Vc/C2 region mediate antinociceptive effects in the craniofacial nociception.

Efferent connections of the ventral auditory area in the rat cortex: implications for auditory processing related to emotion.

In the rat auditory cortex, ventral (VA) and posterodorsal (PD) areas are the two major auditory fields that receive thalamic afferents from the dorsal division of the medial geniculate body (MGD). VA and PD are presumed to serve distinct functions in tandem as the pair of major cortical recipients of extralemniscal thalamic inputs. To deduce the functional significance of VA, efferent connections of VA were examined with the anterograde tracer biocytin. VA lies primarily in the ventral margin of area Te1 and represents frequencies primarily < 15 kHz [Donishi, T., Kimura, A., Okamoto, K. & Tamai, Y. (2006) Neuroscience, 141, 1553-1567.] Biocytin was iontophoretically injected into cortical regions which were defined as VA based on histological location, auditory response and thalamocortical connectivity. Anterograde labelling revealed two important aspects of cortical projections. First, VA sent a projection to a well-confined region in the caudal end of the insular cortex (Ins) pivotal for fear memory formation during aversive conditioning. Second, VA sent parallel projections to cortical regions that probably comprise the other nonprimary auditory fields, including PD. The results suggest that VA relays auditory input from the MGD to the Ins for affective memory formation and at the same time dispatches the auditory signal, which may represent emotional content, to the remaining nonprimary auditory fields. PD is assumed to play a pivotal role in auditory spatial processing for directed attention (Kimura et al., 2004). As the counterpart of PD, VA is assumed to give rise to another major stream of cortical information processing, most probably related to emotion.

Contribution of peripheral 5-HT2A or 5-HT3 receptors to Fos expression in the trigeminal spinal nucleus produced by acute injury to the masseter muscle during persistent temporomandibular joint inflammation in rats.

We investigated the contribution of peripheral 5-HT2A or 5-HT3 receptors to Fos expression in the trigeminal spinal nucleus (VSP) following acute masseter muscle injury in male rats with or without temporomandibular joint (TMJ) inflammation persisting for 7 days. TMJ inflammation was evoked by an injection of complete Freund's adjuvant (CFA). Two hours after formalin injection into the masseter muscle produced Fos-like immunoreactivity (Fos-LI) in several regions of the VSP and upper cervical spinal cord (C2), such as ventrolateral (vl) area of the trigeminal subnucleus caudalis (Vc)/subnucleus interpolaris (Vi) transition (vl-Vi/Vc), paratrigeminal nucleus (dPa5), middle portion of the Vc (mid-Vc) and Vc/C2 transition (Vc/C2) regions in both groups. Significant increases in the number of Fos-LI were observed in these areas in CFA group compared with non-CFA group. TMJ inflammation alone did not induce a significant level of Fos-LI in the VSP. In order to assess the effect of antagonizing 5-HT2A or 5-HT3 receptors on formalin-induced Fos-LI, rats were pre-treated with local (masseter muscle) administration of ketanserin or tropisetron (0.01, 0.1 mg/rat) 20 min prior to formalin injection. In CFA group, these antagonists given locally reduced the Fos-LI response in the laminae I-II at the mid-Vc and Vc/C2 regions. These antagonists reduced the Fos-LI response in the dPa5, but not in the vl-Vi/Vc region. The Fos-LI response was not affected by i.v. administration of ketanserin (0.01, 0.1 mg/rat) or tropisetron (0.01 mg/rat). In non-CFA group, these antagonists given locally did not reduce the Fos-LI response. These results suggest that peripheral 5-HT2A and 5-HT3 receptors contribute to nociceptive processing in the masseter muscle in TMJ inflammatory conditions.

"Ventral" area in the rat auditory cortex: a major auditory field connected with the dorsal division of the medial geniculate body.

The rat auditory cortex is made up of multiple auditory fields. A precise correlation between anatomical and physiological areal extents of auditory fields, however, is not yet fully established, mainly because non-primary auditory fields remain undetermined. In the present study, based on thalamocortical connection, electrical stimulation and auditory response, we delineated a non-primary auditory field in the cortical region ventral to the primary auditory area and anterior auditory field. We designated it as "ventral" area after its relative location. At first, based on anterograde labeling of thalamocortical projection with biocytin, ventral auditory area was delineated as a main cortical terminal field of thalamic afferents that arise from the dorsal division of the medial geniculate body. Cortical terminal field (ventral auditory area) extended into the ventral margin of temporal cortex area 1 (Te1) and the dorsal part of temporal cortex area 3, ventral (Te3V), from 3.2-4.6 mm posterior to bregma. Electrical stimulation of the dorsal division of the medial geniculate body; evoked epicortical field potentials confined to the comparable cortical region. On the basis of epicortical field potentials evoked by pure tones, best frequencies were further estimated at and around the cortical region where electrical stimulation of the dorsal division of the medial geniculate body evoked field potentials. Ventral auditory area was found to represent frequencies primarily below 15 kHz, which contrasts with our previous finding that the posterodorsal area, the other major recipient of the dorsal division of the medial geniculate body; projection, represents primarily high frequencies (>15 kHz). The posterodorsal area is thought to play a pivotal role in auditory spatial processing [Kimura A, Donishi T, Okamoto K, Tamai Y (2004) Efferent connections of "posterodorsal" auditory area in the rat cortex: implications for auditory spatial processing. Neuroscience 128:399-419]. The ventral auditory area, as the other main cortical region that would relay auditory input from the dorsal division of the medial geniculate body to higher cortical information processing, could serve an important extralemniscal function in tandem with the posterodorsal area. The results provide insight into structural and functional organization of the rat auditory cortex.

Topography of projections from the primary and non-primary auditory cortical areas to the medial geniculate body and thalamic reticular nucleus in the rat.

The functional significance of parallel and redundant information processing by multiple cortical auditory fields remains elusive. A possible function is that they may exert distinct corticofugal modulations on thalamic information processing through their parallel connections with the medial geniculate body and thalamic reticular nucleus. To reveal the anatomical framework for this function, we examined corticothalamic projections of tonotopically comparable subfields in the primary and non-primary areas in the rat auditory cortex. Biocytin was injected in and around cortical area Te1 after determining best frequency at the injection site on the basis of epicortical field potentials evoked by pure tones. The rostral part of area Te1 (primary auditory area) and area temporal cortex, area 2, dorsal (Te2D) (posterodorsal auditory area) dorsal to the caudal end of area Te1, which both exhibited high best frequencies, projected to the ventral zone of the ventral division of the medial geniculate body. The caudal end of area Te1 (auditory area) and the rostroventral part of area Te1 (a part of anterior auditory field), which both exhibited low best frequencies, projected to the dorsal zone of the ventral division of the medial geniculate body. In contrast to the similar topography in the projections to the ventral division of the medial geniculate body, collateral projections to the thalamic reticular nucleus terminated in the opposite dorsal and ventral zones of the lateral and middle tiers of the nucleus in each pair of the tonotopically comparable cortical subfields. In addition, the projections of the non-primary cortical subfields further arborized in the medial tier of the thalamic reticular nucleus. The results suggest that tonotopically comparable primary and non-primary subfields in the auditory cortex provide corticofugal excitatory effects to the same part of the ventral division of the medial geniculate body. On the other hand, corticofugal inhibition via the thalamic reticular nucleus may operate in different parts of the ventral division of the medial geniculate body or different thalamic nuclei. The primary and non-primary cortical auditory areas are presumed to subserve distinct gating functions for auditory attention.

Central serotonin 3 receptors play an important role in the modulation of nociceptive neural activity of trigeminal subnucleus caudalis and nocifensive orofacial behavior in rats with persistent temporomandibular joint inflammation.

The role of central serotonin 3 receptors on neural activities recorded from superficial laminae of trigeminal subnucleus caudalis/upper cervical spinal cord junction region was investigated using rats with (Complete Freund's Adjuvant day 7 group) or without (non-Complete Freund's Adjuvant group) persistent temporomandibular joint inflammation evoked by Complete Freund's Adjuvant for 7 days. We identified two types of units, Deep-wide dynamic range units and Skin-wide dynamic range units from extracellular recordings. Deep-wide dynamic range units have mechanoreceptive fields in the deep craniofacial tissues including masseter muscle but do not have cutaneous mechanoreceptive fields. Deep-wide dynamic range unit discharges evoked by the formalin injection into masseter muscle were significantly enhanced in the late phase in Complete Freund's Adjuvant day 7 group. Discharges of Skin-wide dynamic range units evoked by the noxious pinch stimulation to facial skin in Complete Freund's Adjuvant day 7 group were significantly enhanced compared with those in non-Complete Freund's Adjuvant group. Topical administration of central serotonin 3 receptor antagonist, tropisetron, onto trigeminal subnucleus caudalis/upper cervical spinal cord junction region significantly reduced both formalin-evoked Deep-wide dynamic range unit and pinch-evoked Skin-wide dynamic range unit discharges in non-Complete Freund's Adjuvant and Complete Freund's Adjuvant day 7 groups significantly. The inhibitory effects of tropisetron on pinch-evoked Skin-wide dynamic range unit discharges were prolonged in Complete Freund's Adjuvant day 7 group compared with those in non-Complete Freund's Adjuvant group. The role of central serotonin 3 receptors in trigeminal subnucleus caudalis/upper cervical spinal cord junction region was also tested by orofacial formalin test in Complete Freund's Adjuvant day 7 group. Intracisternal administration of tropisetron decreased the orofacial nocifensive behavior in the late phase evoked by the injection of formalin into the masseter muscle. These results suggest that central serotonin 3 receptors in trigeminal subnucleus caudalis/upper cervical spinal cord junction region are involved in mediating pronociceptive effects in both superficial and deep craniofacial tissues nociception during persistent temporomandibular joint inflammation.

The role of peripheral 5HT2A and 5HT1A receptors on the orofacial formalin test in rats with persistent temporomandibular joint inflammation.

The role of peripheral serotonin (5HT) 2A and 5HT1A receptors on the orofacial nocifensive behavioral activities evoked by the injection of formalin into the masseter muscle was evaluated in the rats with persistent temporomandibular joint (TMJ) inflammation evoked by Complete Freund's Adjuvant (CFA). The orofacial nocifensive behavioral activities evoked by the injection of formalin into masseter muscle were significantly enhanced at 1 day (CFA day 1 group) or 7 days (CFA day 7 group) during TMJ inflammation. Pretreatment with local administration of 5HT2A receptor antagonist, ketanserin (0.01, 0.1 mg/rat) into the masseter muscle or systemic administration of ketanserin via i.p. injection (1 mg/kg) reduced the orofacial nocifensive behavioral activities of the late phase evoked by formalin injection into masseter muscle on the side of TMJ inflammation (CFA day 7 group). However, local (0.001-0.1 mg/rat) or systemic (1 mg/kg) administration of 5HT1A receptor antagonist, propranolol, into masseter muscle did not produce the antinociceptive effect in CFA day 7 group. Moreover, local administration of ketanserin (0.1 mg) or propranolol (0.1 mg) into masseter muscle did not inhibit nocifensive orofacial behavior in rats without TMJ inflammation. These data suggest that persistent TMJ inflammation causes the elevation of the orofacial nocifensive behavior, and peripheral 5HT2A receptors play an important role in mediating the deep craniofacial tissue nociception in rats with TMJ inflammation.

Allocation of 14C-carbon in two species of larch seedlings infected with ectomycorrhizal fungi.

The flow of labeled carbon in ectomycorrhizal and non-ectomycorrhizal seedlings of Japanese larch (Larix kaempferi Sarg.) and its F1 hybrid (Larix gmelinii Rupr. x L. kaempferi) was studied. Larch seedlings were grown in a greenhouse for 110 days with larch forest soil (FM) or Suillus grevillei (SM) inoculum, or in the absence of ectomycorrhizal fungi (NM). Shoots of colonized and NM seedlings were exposed to a pulse of 14CO2 for 1 h under natural light. Seedlings were harvested following 0, 6 and 24 h of exposure to 14CO2. At the final harvest, SM seedlings of Japanese larch and hybrid larch allocated 2.6 and 2.5% more 14C, respectively, to roots than NM seedlings. In contrast, FM seedlings of Japanese larch and hybrid larch allocated 6.5 and 18.0% more 14C, respectively, to the stem than NM seedlings. Of the total 14C detected in needle, stem and root fractions, FM and SM seedlings allocated a greater proportion than NM seedlings, perhaps because FM and SM seedlings had significantly (P < 0.05) higher photosynthetic rates than NM seedlings. As a result, FM and SM seedlings had greater dry masses than NM seedlings. Concentrations of nitrogen and phosphorus in FM and SM seedlings were significantly (P < 0.05) higher than in NM seedlings, as was stomatal conductance.

Efferent connections of "posterodorsal" auditory area in the rat cortex: implications for auditory spatial processing.

We examined efferent connections of the cortical auditory field that receives thalamic afferents specifically from the suprageniculate nucleus (SG) and the dorsal division (MGD) of the medial geniculate body (MG) in the rat [Neuroscience 117 (2003) 1003]. The examined cortical region was adjacent to the caudodorsal border (4.8-7.0 mm posterior to bregma) of the primary auditory area (area Te1) and exhibited relatively late auditory response and high best frequency, compared with the caudal end of area Te1. On the basis of the location and auditory response property, the cortical region is considered identical to "posterodorsal" auditory area (PD). Injections of biocytin in PD revealed characteristic projections, which terminated in cortical areas and subcortical structures that play pivotal roles in directed attention and space processing. The most noticeable cortical terminal field appeared as dense plexuses of axons in area Oc2M, the posterior parietal cortex. Small terminal fields were scattered in area frontal cortex, area 2 that comprises the frontal eye field. The subcortical terminal fields were observed in the pontine nucleus, the nucleus of the brachium inferior colliculus, and the intermediate and deep layers of the superior colliculus. Corticostriatal projections targeted two discrete regions of the caudate putamen: the top of the middle part and the caudal end. It is noteworthy that the inferior colliculus and amygdala virtually received no projection. Corticothalamic projections terminated in the MGD, the SG, the ventral zone of the ventral division of the MG, the ventral margin of the lateral posterior nucleus (LP), and the caudodorsal part of the posterior thalamic nuclear group (Po). Large terminals were found in the MGD, SG, LP and Po besides small terminals, the major component of labeling. The results suggest that PD is an auditory area that plays an important role in spatial processing linked to directed attention and motor function. The results extend to the rat findings from nonhuman primates suggesting the existence of a posterodorsal processing stream for auditory spatial perception.

Simultaneous expression of COX-2 and mPGES-1 in mouse gastrointestinal hamartomas.

Cyclo-oxygenase (COX)-2 is induced in various types of cancer tissues. Here, we demonstrate stromal expression of both COX-2 and microsomal prostaglandin E(2) synthase (mPGES)-1 in gastrointestinal hamartomas developed in Lkb1(+/-), Smad4(+/-) and Cdx2(+/-)mice. These results suggest that PGE(2) produced by COX-2 and mPGES-1 plays an important role in hamartoma development regardless of the mutated genes causing hamartomas.

Topography of corticothalamic projections from the auditory cortex of the rat.

Corticothalamic projections from cortical auditory field to the medial geniculate body (MG) in the rat were systematically examined by making small injections of biocytin in cortical area Te1. All injections, confined to 400 microm in diameter, resulted in two projections terminating in the ventral (MGV) and dorsal divisions (MGD) of the MG. The projections to the MGV were evidently topographic. The rostral and caudal portions of area Te1 projected to the ventromedial and dorsolateral parts of the MGV, respectively, forming narrow bands of terminal axons that extended in the mediolateral direction in the coronal plane of the MGV. The minimum dorsoventral width of the bands ranged approximately from 100 to 300 microm. Besides, the more rostral portion of area Te1 tended to project to the more rostral side of the MGV. The projections to the MGD consistently arborized in its ventral margin made up of the deep dorsal nucleus of the MGD. A similar weak topography along the rostrocaudal direction was observed in the projections to the MGD. Large terminals were occasionally found in the MGD after the injections involving cortical layer V. The distribution of large terminals also appeared topographic along with small terminals that were the major component of labeling. Collaterals of labeled axons produced slabs of terminal field in the thalamic reticular nucleus, which also exhibited a weak topography of distribution. These results provide insights into the structural basis of corticofugal modulations related to the tonotopic organizations in the cortex and MG.

Auditory thalamic nuclei projections to the temporal cortex in the rat.

Thalamocortical projections from the auditory thalamic nuclei were examined systematically in the rat, including those from the dorsal division (MGD) of the medial geniculate body (MG), which were less clearly determined in previous studies. Injections of biocytin confined in each thalamic nucleus revealed characteristic features of projections in terms of cortical areas and layers of termination. In contrast to exclusively selective projections to cortical area Te1 from the ventral division (MGV) of the MG, diffuse and selective terminations were observed in the projections from the dorsal (MGD) and medial divisions (MGM) of the MG and the suprageniculate nucleus (SG). Diffuse termination was continuous in layer I or VI of the temporal cortex, while selective termination was in layers III and IV of discrete cortical areas. In addition to diffuse termination in the upper half of layer I of cortical areas Te1, Te2d and Te3v, the MGD and SG projections formed plexuses of axons selectively in lower layer III and layer IV of Te2d and Te3v. The SG projections targeted further the dorsal bank of the perirhinal cortex (PRh), while the MGD projections targeted in part the ventral fringe of Te1. The MGM projections terminated diffusely in layer VI of Te1 and Te3v, and selectively in lower layer III and layer IV of the rostral part of Te3v. Diffuse projections to layers I and VI from the SG and MGM extended in cortical regions over the dorsal fringe of Te1. Selective dense projections to middle cortical layers of Te2d and Te3v (especially its rostral part) indicate the existence of auditory areas, which could be involved in cross-modal interaction with visual and somatosensory system, respectively. Diffuse projections are supposed to bind information processings in these areas and the primary auditory area (Te1).

Peptides from the N-terminal end of bovine lactoferrin induce apoptosis in human leukemic (HL-60) cells.

To determine the effects of the multifunctional iron-binding glycoprotein, lactoferrin (LF) and related compounds on the growth of leukemic cells, human myeloid leukemic cells (HL-60) were exposed to bovine lactoferrin (bLF) and proteolytic hydrolysates of bLF. Pepsin hydrolysates of bLF showed a greater growth suppressive effect than tryptic hydrolysates or mature bLF. Four peptides with proliferation inhibition activity were purified from pepsin hydrolysates by ion-exchange chromatography, reverse-phase HPLC, and gel-filtration. All peptides were from the N-terminal end, in a region where lactoferricin B (Lfcin B), an antibacterial peptide, is located. Among the four peptides, peptide 1 (pep1) was found to exhibit highest activity and corresponded to residues 17 to 38 of bLF, with a molecular weight of 2753.88. The IC50 value of this peptide was 6.3 micrograms/ml. Three other peptides were less active and corresponded to sequences 1 to 16 and 45 to 48, linked by disulfide-bridge (pep2, molecular mass of 2430.13), 1 to 15 and 45 to 46 linked by disulfide bridge (pep3, molecular mass of 2017,92) and from residues 1 to 13 (pep4, molecular mass of 1558.73). Cell proliferation inhibition activity of the peptides was thought to be due to induction of apoptosis, which was evaluated by DNA ladder formation, DNA fragmentation, enhanced expression of phosphatidyl serine, and morphological changes. The IC50 values of the three peptides were confirmed using synthetic peptides and were consistent with those of purified peptides.