A phase II trial of paclitaxel plus biweekly cetuximab for patients with recurrent or metastatic head and neck cancer previously treated with both platinum-based chemotherapy and anti-PD-1 antibody.

BACKGROUND: An important unmet need for new treatment options remains for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) previously treated with both platinum-based chemotherapy and anti-programmed cell death protein 1 (PD-1) antibody. Retrospective studies suggest that previous treatment with immune checkpoint inhibitor might augment the efficacy of subsequent chemotherapy. Here, we conducted a phase II trial aimed to evaluate the efficacy and safety of paclitaxel plus biweekly cetuximab for patients in this setting. PATIENTS AND METHODS: This was a single-arm, multicenter, phase II trial. Key eligibility criteria were R/M-HNSCC, and previous treatment with both platinum-based chemotherapy and PD-1 antibody. Paclitaxel plus biweekly cetuximab consisted of weekly paclitaxel 100 mg/m2 (days 1, 8, 15) and biweekly cetuximab 500 mg/m2 (days 1, 15) with a cycle of 28 days until progression or unacceptable toxicity. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs) (Common Terminology Criteria for Adverse Events version 5.0). RESULTS: Between August 2020 and August 2022, 35 patients were enrolled, of whom 33 were assessable for response. ORR was 69.6% (95% confidence interval 51.2% to 84.4%). With a median follow-up period for survivors of 16.6 months, median PFS and OS were 5.5 and 13.3 months, respectively. DCR was 93.7%. Twenty-three patients (65%) experienced grade 3 or 4 AEs, including neutropenia (34%), infection (14%), leukopenia (11%), mucositis (8%), and pneumonitis (8%). Eight patients discontinued study treatment due to treatment-related AEs, and no treatment-related death was observed. CONCLUSIONS: Paclitaxel plus biweekly cetuximab showed highly encouraging efficacy and manageable toxicities in R/M-HNSCC patients previously treated with both platinum-based chemotherapy and PD-1 antibody. This combination therapy warrants further investigation in this setting.

Radial incision and cutting method for refractory stricture after nonsurgical treatment of esophageal cancer.

Strictures remaining after nonsurgical treatment for esophageal cancer are generally more refractory to endoscopic balloon dilation (EBD) when compared with anastomotic strictures. The aim of the present study was to evaluate the efficacy and safety of a radial incision and cutting (RIC) method for the treatment of refractory strictures after nonsurgical treatment of esophageal cancer. All subjects complained of grade 2 or worse dysphagia, even after at least 10 sessions of EBD. Between August 2009 and May 2012, eight consecutive patients with refractory esophageal stricture after nonsurgical treatments, including chemoradiotherapy (CRT) alone (n = 3), CRT followed by salvage endoscopic treatment (n = 3), or endoscopic submucosal dissection (ESD; n = 2), underwent the RIC procedure. After the RIC procedure, dysphagia in all the patients dramatically improved to grade 1 or 0 without any major complications; however, the long-term efficacy was unfavorable as only 37.5 % (3 /8) demonstrated adequate lumen patency at 3 months, and re-intervention was necessary in six patients (75 %).

Dynamic changes in RAS gene status in circulating tumour DNA: a phase II trial of first-line FOLFOXIRI plus bevacizumab for RAS-mutant metastatic colorectal cancer (JACCRO CC-11).

BACKGROUND: Few prospective studies have used liquid biopsy testing in RAS-mutant metastatic colorectal cancer (mCRC), and its clinical significance remains unknown. Therefore, this study aimed to carry out a biomarker analysis by liquid biopsy using updated data of the phase II trial of FOLFOXIRI plus bevacizumab as first-line chemotherapy for RAS-mutant mCRC. MATERIALS AND METHODS: A total of 64 patients who received modified FOLFOXIRI regimen (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, levofolinate 200 mg/m2, and fluorouracil 2400 mg/m2) plus bevacizumab biweekly were enrolled. The primary endpoint was the objective response rate (ORR). Plasma samples were collected at pre-treatment, 8 weeks after treatment, and progression in participants included in the biomarker study. The levels of circulating tumour DNA (ctDNA) and specific KRAS and NRAS variants were evaluated using real-time PCR assays. RESULTS: There were 62 patients (median age: 62.5 years, 92% performance status 0, 27% right side) who were assessable for efficacy and 51 for biomarker analysis. ORR was 75.8% (95% confidence interval 65.1% to 86.5%). The median progression-free survival was 12.1 months, and the median overall survival (OS) was 30.2 months. In 78% of patients, RAS mutations disappeared in the ctDNA at 8 weeks after treatment; these patients tended to have better outcomes than those with RAS mutations. Interestingly, RAS mutations remained undetectable during progression in 62% of patients. Survival analysis indicated that the median OS from progression was significantly longer in patients with RAS mutation clearance than in those with RAS mutation in the ctDNA at disease progression (15.1 versus 7.3 months, hazard ratio: 0.21, P = 0.0046). CONCLUSIONS: Our biomarker study demonstrated no RAS mutations in ctDNA at disease progression in 62% of patients with RAS-mutant mCRC. Both OS and post-progression survival were better in patients with clearance of RAS mutations in ctDNA after triplet-based chemotherapy.

Amino acid substitutions in an alpha-helical antimicrobial arachnid peptide affect its chemical properties and biological activity towards pathogenic bacteria but improves its therapeutic index.

Four variants of the highly hemolytic antimicrobial peptide Pin2 were chemically synthesized with the aim to investigate the role of the proline residue in this peptide, by replacing it with the motif glycine-valine-glycine [GVG], which was found to confer low hemolytic activity in a spider antimicrobial peptide. The proline residue in position 14 of Pin2 was substituted by [V], [GV], [VG] and [GVG]. Only the peptide variant with the proline substituted for [GVG] was less hemolytic compared to that of all other variants. The peptide variant [GVG] kept its antimicrobial activity in Muller-Hilton agar diffusion assays, whereas the other three variants were less effective. However, all Pin2 antimicrobial peptide variants, were active when challenged against a Gram-positive bacteria in Muller-Hilton broth assays suggesting that chemical properties of the antimicrobial peptides such as hydrophobicity is an important indication for antimicrobial activity in semi-solid environments.

Lymphoplasmacytic sclerosing cholangitis: assessment of clinical, CT, and pathological findings.

AIM: To assess the clinical, computed tomography (CT), and pathological findings in patients with lymphoplasmacytic sclerosing cholangitis. MATERIALS AND METHODS: Fifteen consecutive patients (four women and 11 men, mean age 71 years) with lymphoplasmacytic sclerosing cholangitis and without the characteristic features of underlying disorders causing benign biliary strictures were retrospectively recruited. Two radiologists evaluated multiphase contrast-enhanced CT images acquired with 0.5 or 1-mm collimation. One pathologist performed all histological examinations, including IgG4 immunostaining. RESULTS: The intrahepatic biliary ducts showed dilatation in all 15 patients, but only seven presented with jaundice. Although laboratory data were not available in all patients, serum gammaglobulin and IgG levels were elevated in five of six patients and six of eight patients, respectively. Anti-nuclear antibody was detected in three of six patients. The involved biliary ducts showed the following CT findings: involvement of the hilar biliary duct (14/15), a mean wall thickness of 4.9 mm, a smooth margin (10/15), a narrow but visible lumen (6/15), hyper-attenuation during the late arterial phase (9/15), homogeneous hyper-attenuation during the delayed phase (11/11), and no vascular invasion (14/15). Abnormal findings in the pancreas and urinary tract were detected in eight of 15 patients. In 13 patients with adequate specimens, moderate to severe lymphoplasmacytic infiltration associated with dense fibrosis was observed. Infiltration of IgG4-positive plasma cells was moderate or severe in nine patients and minimal or absent in four patients. CONCLUSION: Lymphoplasmacytic sclerosing cholangitis exhibits relatively characteristic clinical and CT findings, although they are not sufficiently specific for differentiation from other biliary diseases.

SAPPHIRE: a randomised phase II study of planned discontinuation or continuous treatment of oxaliplatin after six cycles of modified FOLFOX6 plus panitumumab in patients with colorectal cancer.

BACKGROUND: Fluorouracil (5-FU), leucovorin (LV) and oxaliplatin (FOLFOX) plus panitumumab therapy is a commonly used first-line chemotherapy for metastatic colorectal cancer (mCRC). However, the long-term administration of oxaliplatin is associated with peripheral neuropathy (PN). We investigated whether the planned discontinuation of oxaliplatin after FOLFOX plus panitumumab therapy can maintain efficacy and reduce PN incidence. PATIENTS AND METHODS: Chemotherapy-naive patients with RAS wild-type mCRC, aged ≥20 years, were enrolled and received six cycles of modified FOLFOX6 (mFOLFOX6) plus panitumumab as induction therapy. Patients who completed induction therapy without progression were randomised to mFOLFOX6 plus panitumumab (group A) or to 5-FU/LV plus panitumumab (group B). The primary end-point was the progression-free survival (PFS) rate at 9 months after randomisation. The secondary end-points were PFS, overall survival (OS), time to treatment failure (TTF), response rate (RR) and safety. RESULTS: In total, 164 patients were enrolled; of whom, 113 patients were then randomised (group A, n = 56; group B, n = 57). The median follow-up after randomisation was 19.6 months. The PFS rates at 9 months and median PFS were 46.4% (80% confidence interval [CI], 38.1-54.9) and 9.1 months (95% CI, 8.6-11.1) in group A, compared with 47.4% (80% CI, 39.1-55.8) and 9.3 months (95% CI, 6.0-13.0) in group B, respectively. RR, OS and TTF were also similar in both groups. Grade ≥2 PN incidence was lower in group B (9.3%) than in group A (35.7%). CONCLUSION: Planned discontinuation of oxaliplatin after six cycles of mFOLFOX6 plus panitumumab is a potential treatment option in patients with mCRC, achieving similar efficacy while reducing oxaliplatin-associated PN compared with mFOLFOX6 plus panitumumab. TRIAL REGISTRATION NUMBER: NCT02337946.

A new Certified Reference Material for radionuclides in Irish sea sediment (IAEA-385).

A new Certified Reference Material (CRM) for radionuclides in sediment (IAEA-385) is described and the results of the certification process are presented. Eleven radionuclides ((40)K, (137)Cs, (226)Ra, (228)Ra, (230)Th, (232)Th, (234)U, (238)U, (238)Pu, (239+240)Pu and (241)Am) have been certified and information mass activities with 95% confidence intervals are given for seven other radionuclides ((90)Sr, (210)Pb((210)Po), (235)U, (239)Pu, (240)Pu and (241)Pu). Results for less frequently reported radionuclides ((60)Co, (99)Tc, (134)Cs, (155)Eu, (224)Ra and (239)Np) and information on some activity and mass ratios are also reported. The CRM can be used for quality assurance/quality control of the analysis of radionuclides in sediment samples, for the development and validation of analytical methods and for training purposes.

Functions of a GnRH receptor heterodimer of the ascidian, Ciona intestinalis.

Gonadotropin-releasing hormone (GnRH) is a ten-amino acid peptide hormone that plays pivotal roles in reproduction in vertebrates and octopus. Recently, six GnRH forms (t-GnRH-3-8) and four GnRH receptor subtypes (Ci-GnRHR-1-4) were identified in the protochordate, Ciona intestinalis. In this study, we show the functional modulation of Ci-GnRHR-1 via heterodimerization with the orphan receptor subtype, Ci-GnRHR-4. The dimerization between Ci-GnRHR-1 and R-4 was detected by co-immunoprecipitation and immunoblot analysis. Binding assays confirmed the binding of t-GnRHs to Ci-GnRHR-1 but not to R-4, and verified no alternation in ligand-binding affinity between Ci-GnRHR-1 homodimer and Ci-GnRHRI&4 heterodimer. The heterodimer was found to stimulate the elevation of intracellular calcium, time-extension of ERK phosphorylation, and up-regulation of cell proliferation, all in a ligand specific manner, compared with the Ci-GnRHR-1 homodimer. In combination, these results indicated that Ci-GnRHR-4 is not an inactive receptor, but a modulatory factor for Ci-GnRHR-1 in C. intestinalis.

Neuropeptides and their receptors of the protochordate, Ciona intestinalis: the evolutionary origin of vertebrate neuropeptides.

Ci-TK and Ci-TK-R are authentic tachykinin (TK) and TK receptor isolated from a protochordate, Ciona intestinalis. In this study, we investigated a novel function of TK as an enhancer of oocyte growth. Ci-TK-R is expressed specifically in the Ciona vitellogenic oocytes. Moreover, administration of Ci-TK to the Ciona ovary resulted in upregulation of gene expression and enzymatic activity of several proteases. Moreover, maturation of the Ciona oocytes from the vitellogenic stage to the post-vitellogenic stage was induced in the presence of Ci-TK, which was completely blocked by addition of protease inhibitors.

Antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats.

The purpose of this study was to establish a nude rat orthotopic (organ-specific) human colorectal cancer model as an in vivo secondary screen for general evaluation of new anticancer agents against colorectal cancer and to evaluate practically the antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1), a new p.o. fluoropyrimidine, in comparison to 1 M tegafur-4 M uracil [(UFT) effective on colorectal tumor in clinical]. After implantation of KM12C, a human colorectal cancer cell line, into the subserosal layer of the colon as a single-cell suspension, extensive local tumor growth and invasion to both the mucosal and the serosal sides were observed in all rats. Metastatic foci were also formed in both lymph nodes and lungs following local tumor growth in all of them. Using this method, an equitoxic dose of S-1 (15 mg/kg/day) and UFT (30 mg/kg/day) was administered p.o. for 14 consecutive days from 7 days after tumor cell implantation. S-1 showed a higher tumor growth inhibition than UFT did [S-1, 57% (significantly different from the tumor weight of the untreated group at P < 0.05) and UFT, 18% (P > 0.05)]. When both drugs were administered to nude rats bearing KM12C injected into the cecal wall for 28 consecutive days at equitoxic doses, the mean survival in the S-1 group was 16 days longer than that in the untreated group (P < 0.01) but that in the UFT group was only 8 days longer (P > 0.05). After the administration of an equitoxic dose of both drugs, S-1 gave the higher levels than UFT in various pharmacokinetic parameters as follows: area under the curve 0-24 h of 5-fluorouracil in plasma (3.5-fold), area under the curve 0-24 h of 5-fluorouracil incorporated into RNA in the tumor (1.3-fold), and thymidylate synthase inhibition rate (percentage) in the tumor (about 20%). Collectively, these findings suggested that this orthotopic human colorectal tumor model in nude rats is useful to evaluate the clinical therapeutic efficacy of drugs or therapies for colorectal cancer, and that S-1 had a higher therapeutic effect on human colorectal tumor than UFT did.

Bone-peg grafting for osteochondritis dissecans of the humeral capitellum.

PURPOSE: To review the outcome of bone-peg grafting for osteochondritis dissecans (OCD) grade II lesions of the humeral capitellum. METHODS: Records of 10 male adolescent baseball players aged 10 to 15 (mean, 12.3) years who underwent bone-peg grafting for OCD grade II lesions of the humeral capitellum of the dominant arm were reviewed. The mean time from symptom onset to presentation was 11 (range, 1-36) months. The mean duration of conservative treatment was 5 (range, 1-25) months. The mean time from symptom onset to surgery was 17 (range, 3-39) months; it was >6 months in 6 patients. The mean size of the lesions was 13x14 mm. Patients were assessed for elbow pain, range of elbow and forearm motion, Timmerman- Andrews elbow score, return to sports activity level, and radiographic evidence of healing, osteoarthritic changes, and radial head hypertrophy. RESULTS: The mean follow-up period was 25 (range, 10-52) months. Postoperatively, elbow pain was absent in 6, mild in 2, and moderate in 2 patients. The mean range of elbow motion changed from 136º to 139° (p=0.80). The mean Timmerman-Andrews elbow score improved from 163 to 189 (p=0.014); it was excellent in 7, good in 2, and fair in one patient. The mean extent of lesion healing was 71% (range, 33-100%). Five patients achieved complete healing after a mean of 5.2 (range, 5-6) months and returned to sports at a competitive level. The other 5 achieved partial healing of 33 to 56% (mean, 41%) that occurred laterally but not medially. Two of them returned to sports at a competitive level: one changed the throwing side and another had radial head hypertrophy. The remaining 3 underwent arthroscopic debridement of the unhealed lesion at 5, 10, and 15 months. One patient developed secondary osteoarthritis and further underwent costal osteochondral autografting 10 months later. None of the 5 patients with partial healing versus 4 of the 5 patients with complete healing underwent surgery within 6 months of symptom onset. All 3 patients with a dot at the interface versus 2 of the 6 patients with a line at the interface between the fragment and the lesion on MRI had complete healing. CONCLUSION: Bone-peg grafting is a viable option for OCD grade II lesions of the humeral capitellum when performed within 6 months of symptom onset and when the interface between the fragment and the lesion appears as a dot (rather than a line) on MRI.

Wireless EEG patch sensor on forehead using on-demand stretchable electrode sheet and electrode-tissue impedance scanner.

A wireless electroencephalogram (EEG) sensor using a stretchable electrode sheet and electrode-tissue impedance measurement module is presented herein. The sensor can be attached to the forehead using biocompatible gel with the electrode sheet. The sensor is compactly designed for 3 cm × 9 cm × 6 mm with weight of 12 g. Impedance scanning circuit is also proposed to evaluate the skin surface condition before EEG measurements. We developed the impedance scanning board for 3 cm × 5 cm × 3 mm, with weight of 5.6 g. Results show that the proposed system demonstrates a promising performance in diagnosing the Alzheimer's disease using frequency domain analysis.

Circular dichroism spectra of purified cytochromes P-450 from rabbit liver microsomes.

Circular dichroism (CD) spectra were measured for cytochromes P-450 (P-450) purified from phenobarbital- and 3-methylcholanthrene-induced rabbit liver microsomes. No striking difference in alpha-helix content was seen between phenobarbital-induced P-450 (PB P-450) (50%), phenobarbital-induced P-448 (PB P-448) (40%) and 3-methylcholanthrene-induced P-448 (MC P-448) (45--50%) in terms of ultraviolet CD spectra. Strong negative CD spectra associated with 3-methylcholanthrene transitions for MC P-448 in the near-ultraviolet region (250--310 nm) and weaker negative CD spectra associated with Soret transitions for PBP-448 ([theta] = 50 000) and MCP-448 ([theta] = 160 000), indicated that structures of these preparations are strikingly different from each other. Reduction of P-450 and P-448 led to a remarkable decrease of the Soret CD trough, suggesting that reduction was accompanied by a striking conformational change in the vicinity of the heme. Since CO complexes of reduced P-450 and P-448 showed a CD trough and an S-shaped CD, respectively, associated with the absorption peak at 450 nm, the heme vicinities are remarkably different from each other. The CD spectra in the visible region are also discussed. It was noticed that P-420, the denatured form of P-450, exhibited no CD spectra in the Soret and visible regions.

Characterization of a cDNA encoding a precursor of Carassius RFamide, structurally related to a mammalian prolactin-releasing peptide.

We have characterized the cDNA encoding Carassius RFamide (C-RFa), which is structurally related to mammalian prolactin-releasing peptides (PrRPs), from the brain of the crucian carp. The deduced C-RFa precursor has been shown to comprise 117 amino acids, encoding a single C-RFa sequence. A comparative study of amino acid sequences has revealed that several sequences conserved in preproPrRPs are also found in the C-RFa precursor. Furthermore, the abundant presence of the C-RFa mRNA in the telencephalon, optic tectum, medulla oblongata, and proximal half eye ball was demonstrated by Southern blot analysis of RT-PCR products.

Preclinical antitumor efficacy of S-1: a new oral formulation of 5-fluorouracil on human tumor xenografts.

S-1 is a new oral formulation of 5-fluorouracil (5-FU) consisted of 1M tegafur, 0.4M 5-chloro-2,4-dihydroxypyridine that inhibits a degradation of 5-FU, and 1M potassium oxonate that regulates the phosphorylation of 5-FU in the gastrointestinal tract, and has shown excellent antitumor efficacy against various murine tumors in rodents, compared to the oral tegafur-based antitumor drug, UFT (1M tegafur plus 4M uracil), which is used clinically in Japan. To assess the possibility of clinically using S-1, we investigated the antitumor effect of S-1 on various human solid tumor xenografts in athymic rats and mice. In the nude rat system, S-1 was significantly effective against all 12 tumor xenografts tested when its minimum toxic dose (15 mg/kg) was administered for 14 days. Three tumors, stomach (H-81), colon (KM12C) and breast (H-31) markedly regressed in response to treatment with S-1 but not with UFT. The antitumor potency of S-1 was weak against human tumors xenografted into nude mice and likely similar to that of UFT. The reason of the discrepancy in the efficacy of S-1 between rats and mice was found to be that the 5-FU levels in the blood and tumor tissue of rats after oral administration of S-1 persisted much longer than in mice, and this prolonged maintenance of plasma 5-FU levels was significantly related to the potent antitumor activity of S-1. In conclusion, the results of this study suggested that based on its biological and pharmacokinetic characteristics, oral S-1 should be active against various human cancers.

Multiple forms of cytochrome P-450 purified from liver microsomes of phenobarbital- and 3-methylcholanthrene-pretreated rabbits. I. Resolution, purificaton, and molecular properties.

A method is described for the separation and purification of different forms of cytochrome P-450 from liver microsomes of phenobarbital (PB)- and 3-methylcholanthrene (MC)-pretreated rabbits. It consists of solubilization of microsomes with cholate, followed by successive chromatography on omega-aminooctyl Sepharose 4B, hydroxylapatite and CM-Sephadex C-50 columns. Separation of different forms of cytochrome P-450 is achieved in the aminooctyl Sepharose and hydroxylapatite chromatograhy steps. This method permits the separation of three forms of cytochrome P-450, i.e. "P-450(1)," "P-450(2)," and "P-488(1)," from PB-induced microsomes; P-450(1), the main cytochrome P-450 component in these microsomes, and P-448(1) can each be obtained in a gel-electrophoretically homogeneous state, whereas P-450(2) can be obtained in a partially purified state. Application of the same method to MC-induced microsomes led to the purification of P-448(1), the main component in these microsomes, to homogeneity and to partial purification of a fourth form, i.e. "P-450(3)." P-448(1) from MC-induced microsomes seems to be identical with P-448(1) from PB-induced microsomes in monomeric molecular weight (54,000), amino acid composition and chromatographic behavior. However, P-448(1) from MC-induced microsomes, but not P-448(1) from PB-induced microsomes, contains 0.18 to 0.88 mol of tightly bound MC per mol of protein. P-450(1) has a molecular weight of 49,000 and its amino acid composition is clearly different from that of P-448(1). Although P-450(2) is similar in molecular weight, they differ from each other in chromatographic behavior. P-450(3) seems to be different from P-450(1) in molecular weight, though they are similar to each other in chromatographic behavior. All the cytochrome P-450 preparations can be freed from the detergents used in the purification procedure by CM-Sephadex C-50 chromatography. Detergent-free P-450(1), P-450(2), and P-448(1) exist in aqueous solution as oligomeric aggregates.

Characterization of cDNA and expression of mRNA encoding an Achatina cardioexcitatory RFamide peptide.

Achatina cardioexcitatory peptide-1 (ACEP-1) is an RFamide family peptide isolated from the atria of the African giant snail, Achatina fulica. In this report, we describe an identification of the ACEP-1 cDNA sequence and localizations of the ACEP-1 mRNA. Southern blot analysis revealed that the ACEP-1 mRNA was present in the atrium as well as in the central nervous system. Furthermore, in situ hybridization revealed the localizations of the ACEP-1 mRNA in small neurons of the cerebral and pedal ganglia and a few large neurons of the right parietal and visceral ganglia.

Identification of multiple urechistachykinin peptides, gene expression, pharmacological activity, and detection using mass spectrometric analyses.

Urechistachykinin I and II (Uru-TK I and II) are invertebrate tachykinin-related peptides (TRPs), which have been isolated from echiuroid worms. The cDNA sequence encoding the Uru-TK I and II revealed that the precursor also encoded five TRP-like peptides. Here, we report the characterization of these Uru-TK-like peptides named as Uru-TK III-VII. Northern and Southern blot analyses demonstrated that Uru-TK mRNA is localized in nerve tissue. In addition, the presence of the Uru-TK-like peptides as matured forms in the nerve tissue was detected by mass spectrometric analysis, and identified these peptides were shown to exhibit a contractile activity on cockroach hindgut that was as potent as that of Uru-TK II. Furthermore, synthetic Uru-TK-like peptide analogs which contained Met-NH2 instead of Arg-NH2 at their C-termini were shown to possess a potential to bind to a mammalian tachykinin receptor, indicating that Uru-TK-like peptides are likely to correspond to vertebrate tachykinins, except for the difference at the C-terminal residue. These findings show that Uru-TK-like peptides are essentially equivalent to Uru-TK I and II, leading to the proposal that Uru-TK-like peptides play an essential role as invertebrate tachykinin neuropeptides.

Neuronal responses to vestibular and callosal stimulation in the anterior suprasylvian gyrus of the cat.

Neuronal responses to electrical stimulation at the horizontal ampulla (HA), vestibular nerve (at the windows) and corpus callosum (CC) were investigated in neurons in the anterior suprasylvian gyrus of the cat. The field potentials to HA stimulation had short latency: 2.9 +/- 0.3 (mean +/- SD) ms from the stimulus to the onset and 5.6 +/- 1.9 ms to the peak. The focus of the evoked potentials was located in the anterior suprasylvian (ASS) gyrus or near the ASS sulcus. HA stimulation activated 6 neurons out of 674 examined, with the mean latency of 4.3 +/- 1.1 ms. Of these 6, four neurons also responded to window stimulation. Fifty-six neurons responded to window stimulation with the mean latency of 6.1 +/- 2.4 ms. The mean latency for CC stimulation was 1.9 +/- 0.9 ms (n = 76). Four neurons responded to CC stimulation antidromically (mean = 0.9 +/- 0.3 ms) and one of them also responded orthodromically. The convergence of CC inputs in relation to HA or window stimulation was examined. One (17%) of the 6 HA-activated cells responded to CC stimulation, compared with 8 (14%) of the 56 neurons activated by window stimulation. The other 612 neurons did not respond to either HA or window stimulation, and 80 (13%) of the 612 responded to CC stimulation. Therefore, it is concluded that neurons in the ASS gyrus received callosal input equally irrespective of the presence or absence of responses to ampulla or window stimulation. WGA-HRP was injected in the ASS gyrus to identify the passing callosal fibers in the CC. Fibers from the ASS area passed at the rostral third of the CC. The present results indicate that the ASS area received vestibular projection with short latency, but responses of this projection did not seem to be very strong, at least from the present unit study, to HA stimulation. Discussion was made on the poor neuronal responses to electrical HA stimulation in comparison with previous studies. Also consideration was made on neuronal activity to CC stimulation.