The impact of nutritional status in nivolumab-treated patients with advanced esophageal cancer.

Although phase III trials have reported improved overall survival in patients with advanced esophageal squamous cell carcinoma following treatment with nivolumab, as compared with chemotherapy (paclitaxel or docetaxel), the treatment was effective only in a limited number of patients. Therefore, the aim of this study is to determine whether there is a correlation between nutritional status (Glasgow prognostic score, prognostic nutritional index, and neutrophil-to-lymphocyte ratio) and prognosis of advanced esophageal cancer in patients treated with taxane or nivolumab therapy. The medical records of 35 patients who received taxane monotherapy (paclitaxel or docetaxel), for advanced esophageal cancer between October 2016 and November 2018 (taxane cohort) were reviewed. The clinical data of 37 patients who received nivolumab therapy between March 2020 and September 2021 (nivolumab cohort) were collected. The median overall survival was 9.1 months for the taxane cohort and 12.5 months for the nivolumab cohort. In the nivolumab cohort, patients with good nutritional status had significantly better median overall survival than those with poor nutritional status (18.1 vs. 7.6 months, respectively, p = 0.009, classified by prognostic nutritional index, 15.5 vs. 4.3 months, respectively, p = 0.012, classified by Glasgow prognostic score), whereas the prognosis of the patients treated with taxane therapy was less affected by the nutritional status. This suggests that the pretreatment nutritional status of patients with advanced esophageal cancer is a key factor for successful outcomes, especially for treatment with nivolumab.

Assessment of photodynamic therapy as a salvage treatment for local failure after chemoradiotherapy or radiotherapy for esophageal cancer in patients aged 80 years or older.

Objectives: Chemoradiotherapy (CRT) or radiotherapy (RT) alone is often the treatment of choice for elderly patients with esophageal cancer with the expectation of organ preservation. However, salvage treatment remains a problem when endoscopic resection is not indicated for local failure after CRT/RT. Photodynamic therapy (PDT) is indicated for local failure after CRT/RT, but there are few reports on its efficacy and safety in elderly patients. This study aimed to assess the outcome of PDT for local failure after CRT/RT for esophageal cancer in elderly patients. Methods: This retrospective single-center study included 42 patients who first underwent PDT between April 2013 and June 2021. Patients aged ≥80 and <80 years were classified into the elderly and nonelderly groups, respectively. Local complete response rate, overall survival, progression-free survival, and incidence of adverse events related to PDT were compared retrospectively between the groups. Results: The local complete response rate was 93.3% in the elderly group and 85.7 in the non-elderly group. The 2-year overall survival rate was 68.6% and 72.5%, and the 2-year progression-free survival rate was 49.5% and 70.0% in the elderly and nonelderly groups, respectively. There was no significant difference in any of these outcomes between the groups. In terms of adverse events, pneumonia and delirium tended to occur more frequently in the elderly group, but there were no serious adverse events in either group. Conclusion: The outcome of salvage PDT in the local control was comparable between the elderly and nonelderly patients for local failure after CRT/RT for esophageal cancer.

Pretreatment Glasgow prognostic score as a predictor of outcomes in nivolumab-treated patients with advanced gastric cancer.

In Japan, South Korea, and Taiwan, nivolumab might provide overall survival benefits for patients with advanced gastric cancer. However, it is effective only in a limited number of patients. The Glasgow prognostic score is an indicator of the systematic inflammatory response and nutritional status. This study aimed to investigate the ability of the Glasgow prognostic score and other markers to predict the outcomes of patients treated with nivolumab. We reviewed the medical records of patients treated for advanced gastric cancer and who received nivolumab between February 2015 and June 2019 at Hyogo Cancer Center. The patients were categorized into two groups according to their Glasgow prognostic scores. Overall, 53.3% and 46.7% of the patients were assigned to groups with Glasgow prognostic scores of 0 and 1/2, respectively. The median durations of progression-free and overall survival of the participants were 2.3 and 5.7 months, respectively. The patients with a Glasgow prognostic score of 0 had significantly higher median overall survival than those with scores of 1 or 2 (16.4 vs. 4.2 months; p = 0.0006). This observation suggests that a pretreatment Glasgow prognostic score of 0 is associated with better outcomes, and this scoring system may be used as a predictor of outcomes in patients with advanced gastric cancer treated with nivolumab.

A comparison of the resection rate for cold and hot snare polypectomy for 4-9 mm colorectal polyps: a multicentre randomised controlled trial (CRESCENT study).

OBJECTIVE: To investigate the success rate of cold snare polypectomy (CSP) for complete resection of 4-9 mm colorectal adenomatous polyps compared with that of hot snare polypectomy (HSP). DESIGN: A prospective, multicentre, randomised controlled, parallel, non-inferiority trial conducted in 12 Japanese endoscopy units. Endoscopically diagnosed sessile adenomatous polyps, 4-9 mm in size, were randomly assigned to the CSP or HSP group. After complete removal of the polyp using the allocated technique, biopsy specimens from the resection margin after polypectomy were obtained. The primary endpoint was the complete resection rate, defined as no evidence of adenomatous tissue in the biopsied specimens, among all pathologically confirmed adenomatous polyps. RESULTS: A total of 796 eligible polyps were detected in 538 of 912 patients screened for eligibility between September 2015 and August 2016. The complete resection rate for CSP was 98.2% compared with 97.4% for HSP. The non-inferiority of CSP for complete resection compared with HSP was confirmed by the +0.8% (90% CI -1.0 to 2.7) complete resection rate (non-inferiority p<0.0001). Postoperative bleeding requiring endoscopic haemostasis occurred only in the HSP group (0.5%, 2 of 402 polyps). CONCLUSIONS: The complete resection rate for CSP is not inferior to that for HSP. CSP can be one of the standard techniques for 4-9 mm colorectal polyps. (Study registration: UMIN000018328).

Obstructive sleep apnea in preschool-aged Japanese children - efficiency of screening using lateral neck radiography.

Conclusions The prevalence of obstructive sleep apnea (OSA) in preschool-aged children diagnosed by the International Classification of Sleep Disorders (ICSD) version 3 criteria was relatively higher than that diagnosed by ICSD-2. Although the assessment of the upper airway by lateral neck radiography was effective for detecting OSA in this age group, this assessment is not recommended for all children as a screening method because of parental concern related to radiation exposure. Objective This study investigated the prevalence of OSA and the screening capacity of lateral neck radiography in community-based preschool-aged children. Methods Parents of 211 children aged 3-6 years were requested to complete the sleep-related questionnaire. Subjects who agreed to further investigations were invited to undergo home type 3 portable monitoring and clinical examination, including radiography. We estimated the prevalence of OSA and evaluated the detection power of radiography for predicting OSA. Results One hundred and eighty-eight (89.1%) subjects completed the questionnaire and 67 (31.8%) agreed to further examinations. The weighted prevalence was 7.3% and 12.8% by ICSD-2 and 3, respectively. Area under the receiver operator curve for the adenoidal/nasopharyngeal and tonsil/pharyngeal ratios measured using radiography was slightly larger than that for tonsil size graded by visual inspection.

Prevalence of obstructive sleep apnea syndrome in Japanese elementary school children aged 6-8 years.

PURPOSE: We aimed to determine the prevalence of and the risk factors for obstructive sleep apnea syndrome (OSAS) in Japanese children aged 6-8 years. METHODS: The parents of 202 children aged 6-8 years who attended a single elementary school in Shiga, Japan, were requested to complete the Child and Adolescent Sleep Checklist (CASC) and perform home Type 3 portable monitoring of their children. By using the CASC data and monitor recordings, we estimated the prevalence of pediatric OSAS with the help of different diagnostic criteria and identified the risk factors associated with OSAS. RESULTS: Complete data were obtained from 170 of the 194 children whose parents participated in the study. The mean total apnea-hypopnea index and obstructive apnea hypopnea index were 1.4 ± 1.3 and 0.4 ± 0.6 h(-1), respectively, and central apnea was the most prevalent type of respiratory event, accounting for 70.4% of all events. The overall prevalence of OSAS ranged from 0.6% to 43.5%, depending on the cutoff value used, and was 3.5% when using International Criteria of Sleep Disorders version II (ICSD II) diagnostic criteria. The presence of tonsillar hypertrophy was the only parameter whose prevalence was significantly elevated in children with OSAS across all diagnostic criteria. CONCLUSIONS: The prevalence of pediatric OSAS varies according to the diagnostic criteria used, indicating the need for further research focusing on outcomes to define a clinically significant diagnostic threshold. The presence of tonsillar hypertrophy is an important risk factor in the development of pediatric OSAS.

A new modification of uvulopalatopharyngoplasty for the treatment of obstructive sleep apnea syndrome.

OBJECTIVE: To evaluate objective and subjective improvement after applying a new surgical technique, two-piece palatopharyngoplasty (Two-P4), to the treatment of obstructive sleep apnea syndrome (OSAS). METHODS: Twenty-four patients with mild to severe OSAS underwent Two-P4 between January 2002 and November 2007. Polysomnography and Epworth Sleepiness Scale (ESS) score were used to evaluate surgical results. RESULTS: Mean apnea-hypopnea index (AHI) improved from 50.9 to 10.7 after Two-P4. Mean ESS score decreased significantly from 13.0 to 7.7. Body mass index was unchanged after surgery. Objective success as evaluated by a 50% reduction in AHI and by AHI <20 was obtained in 22 of 24 patients (91.7%). Mean reduction in AHI was 76.9% for all 24 patients, 86.2% for patients with Friedman's anatomical stage I, 78.9% for stage II, and 54.5% for stage III. CONCLUSION: Two-P4 is a novel surgical treatment for OSAS patients with a high success rate (91.7%) as evaluated by reductions in AHI. Two-P4 keeps the middle soft palate intact to form independent scars on both sides, which constrict to stretch the soft palate and widen the pharyngeal space.

Sensillum-specific, topographic projection patterns of olfactory receptor neurons in the antennal lobe of the cockroach Periplaneta americana.

In vertebrates and many invertebrates, olfactory signals detected by peripheral olfactory receptor neurons (ORNs) are conveyed to a primary olfactory center with glomerular organization in which odor-specific activity patterns are generated. In the cockroach, Periplaneta americana, ORNs in antennal olfactory sensilla project to 205 unambiguously identifiable antennal lobe (AL) glomeruli that are classified into 10 glomerular clusters (T1-T10 glomeruli) innervated by distinct sensory tracts. In this study we employed single sensillum staining techniques and investigated the topographic projection patterns of individual ORNs to elucidate the relationship between sensillum types and glomerular organization in the AL. Axons of almost all ORNs projected to individual glomeruli. Axons of ORNs in perforated basiconic sensilla selectively innervated the anterodorsal T1-T4 glomeruli, whereas those in trichoid and grooved basiconic sensilla innervated the posteroventral T5-T9 glomeruli. About 90% of stained ORNs in trichoid sensilla sent axons to the T5 glomeruli and more than 90% of ORNs in grooved basiconic sensilla innervated the T6, T8, and T9 glomeruli. The T5 and T9 glomeruli exclusively receive sensory inputs from the trichoid and grooved basiconic sensilla, respectively. All investigated glomeruli received convergent input from a single type of sensillum except F11 glomerulus in the T6 glomeruli, which was innervated from both trichoid and grooved basiconic sensilla. These results suggest that ORNs in distinct sensillum types project to glomeruli in distinct glomerular clusters. Since ORNs in distinct sensillum types are each tuned to distinct subsets of odorant molecules, the AL is functionally compartmentalized into groups of glomeruli.

Higher brain centers for social tasks in worker ants, Camponotus japonicus.

Ants, eusocial insects, have highly elaborate chemical communication systems using a wide variety of pheromones. In the carpenter ant, Camponotus japonicus, workers and queens have the female-specific basiconic sensilla on antennae. The antennal lobe, the primary processing center, in female carpenter ants contains about 480 glomeruli, which are divided into seven groups (T1­T7 glomeruli) based on sensory afferent tracts. The axons of sensory neurons in basiconic sensilla are thought to project to female-specific T6 glomeruli. Therefore, these sensilla and glomeruli are thought to relate to female-specific social tasks in the ants. By using dye filling into local neurons (LNs) and projection neurons (PNs) in the antennal lobe, we neuroanatomically revealed the existence of an isolated processing system for signals probably relating to social tasks in the worker ant. In the antennal lobe, two categories of glomeruli, T6 glomeruli and non-T6 glomeruli, are clearly segregated by LNs. Furthermore, axon terminals of uniglomerular PNs from the respective categories of glomeruli (T6 uni-PNs and non-T6 uni-PNs) are also segregated in the secondary olfactory centers, the calyces of the mushroom body and the lateral horn: T6 uni-PNs terminate in the outer layers of the basal ring and lip of mushroom body calyces and in the posterior region of the lateral horn, whereas non-T6 uni-PNs terminate in the middle and inner layers of the basal ring and lip and in the anterior region of the lateral horn. These findings suggest that information probably relating to social tasks might be isolated from other olfactory information and processed in a separate subsystem.

Complete mapping of glomeruli based on sensory nerve branching pattern in the primary olfactory center of the cockroach Periplaneta americana.

Glomeruli are structural and functional units in the primary olfactory center in vertebrates and insects. In the cockroach Periplaneta americana, axons of different types of sensory neurons housed in sensilla on antennae form dorsal and ventral antennal nerves and then project to a number of glomeruli. In this study, we identified all antennal lobe (AL) glomeruli based on detailed innervation patterns of sensory tracts in addition to the shape, size, and locations in the cockroach. The number of glomeruli is approximately 205, and no sex-specific difference is observed. Anterograde dye injections into the antennal nerves revealed that axons supplying the AL are divided into 10 sensory tracts (T1-T10). Each of T1-T3 innervates small, oval glomeruli in the anteroventral region of the AL, with sensory afferents invading each glomerulus from multiple directions, whereas each of T4-T10 innervates large glomeruli with various shapes in the posterodorsal region, with a bundle of sensory afferents invading each glomerulus from one direction. The topographic branching patterns of all these tracts are conserved among individuals. Sensory afferents in a sub-tract of T10 had axon terminals in the dorsal margin of the AL and the protocerebrum, where they form numerous small glomerular structures. Sensory nerve branching pattern should reflect developmental processes to determine spatial arrangement of glomeruli, and thus the complete map of glomeruli based on sensory nerve branching pattern should provide a basis for studying the functional significance of spatial arrangement of glomeruli and its developmental basis.

Sex-specific antennal sensory system in the ant Camponotus japonicus: glomerular organizations of antennal lobes.

Ants have well-developed chemosensory systems for social lives. The goal of our study is to understand the functional organization of the ant chemosensory system based on caste- and sex-specific differences. Here we describe the common and sex-specific glomerular organizations in the primary olfactory center, the antennal lobe of the carpenter ant Camponotus japonicus. Differential labeling of the two antennal nerves revealed distinct glomerular clusters innervated by seven sensory tracts (T1-T7 from ventral to dorsal) in the antennal lobe. T7 innervated 10 glomeruli, nine of which received thick axon terminals almost exclusively from the ventral antennal nerve. Coelocapitular (hygro-/thermoreceptive), coeloconic (thermoreceptive), and ampullaceal (CO2-receptive) sensilla, closely appositioned in the flagellum, housed one or three large sensory neurons supplying thick axons exclusively to the ventral antennal nerve. These axons, therefore, were thought to project into T7 glomeruli in all three castes. Workers and virgin females had about 140 T6 glomeruli, whereas males completely lacked these glomeruli. Female-specific basiconic sensilla (cuticular hydrocarbon-receptive) contained over 130 sensory neurons and were completely lacking in males' antennae. These sensory neurons may project into T6 glomeruli in the antennal lobe of workers and virgin females. Serotonin-immunopositive neurons innervated T1-T5 and T7 glomeruli but not T6 glomeruli in workers and virgin females. Because males had no equivalents to T6 glomeruli, serotonin-immunopositive neurons appeared to innervate all glomeruli in the male's antennal lobe. T6 glomeruli in workers and virgin females are therefore female-specific and may have functions related to female-specific tasks in the colony rather than sexual behaviors.

Sex-specific antennal sensory system in the ant Camponotus japonicus: structure and distribution of sensilla on the flagellum.

The antennae are a critically important component of the ant's highly elaborated chemical communication systems. However, our understanding of the organization of the sensory systems on the antennae of ants, from peripheral receptors to central and output systems, is poorly understood. Consequently, we have used scanning electron and confocal laser microscopy to create virtually complete maps of the structure, numbers of sensory neurons, and distribution patterns of all types of external sensilla on the antennal flagellum of all types of colony members of the carpenter ant Camponotus japonicus. Based on the outer cuticular structures, the sensilla have been classified into seven types: coelocapitular, coeloconic, ampullaceal, basiconic, trichoid-I, trichoid-II, and chaetic sensilla. Retrograde staining of antennal nerves has enabled us to count the number of sensory neurons housed in the different types of sensilla: three in a coelocapitular sensillum, three in a coeloconic sensillum, one in an ampullaceal sensillum, over 130 in a basiconic sensillum, 50-60 in a trichoid-I sensillum, and 8-9 in a trichoid-II sensillum. The basiconic sensilla, which are cuticular hydrocarbon-receptive in the ant, are present in workers and unmated queens but absent in males. Coelocapitular sensilla (putatively hygro- and thermoreceptive) have been newly identified in this study. Coelocapitular, coeloconic, and ampullaceal sensilla form clusters and show biased distributions on flagellar segments of antennae in all colony members. The total numbers of sensilla per flagellum are about 9000 in unmated queens, 7500 in workers, and 6000 in males. This is the first report presenting comprehensive sensillar maps of antennae in ants.

Behavioral and electrophysiological studies on the sexually biased synergism between oligosaccharides and phospholipids in gustatory perception of nuptial secretion by the German cockroach.

Females of Blattella germanica feed compulsively on a nuptial secretion from the male's eighth tergal gland (TG-8) during courtship. Using TG-8 extract and its essential ingredients, maltotriose (MT) and 1,2-dioleoylphosphatidylcholine (PC), we investigated the perception of the secretion by gustatory sensilla in both sexes. Female-biased chemosensitivity was found in the feeding responses to the TG-8 extract. The TG-8 extract induced specific impulses in four functionally different receptor cells: the sugar, salt and other two types of receptor cells in a single gustatory sensillum on the paraglossae in both sexes. The impulse frequencies of the sugar receptor cell and a receptor cell of unknown type were significantly higher in females than those in males. There were no sexual differences in the behavioral and electrophysiological responses to MT alone; no responses were elicited by PC. However, a mixture of MT and PC elicited the behavioral responses more strongly than MT in females. The impulse frequency of sugar receptor cells toward the mixture of MT and PC also increased in females but not in males. These results suggest that the synergistic effect of PC on 'sweetness' of MT in the female cockroach contributes to her compulsive nuptial feeding. The female-biased gustatory sensitivity seems to ensure successful coupling during the nuptial feeding.

Functional and topographic segregation of glomeruli revealed by local staining of antennal sensory neurons in the honeybee Apis mellifera.

In the primary olfactory center of animals, glomeruli are the relay stations where sensory neurons expressing cognate odorant receptors converge onto interneurons. In cockroaches, moths, and honeybees, sensory afferents from sensilla on the anterodorsal surface and the posteroventral surface of the flagellum form two nerves of almost equal thicknesses. In this study, double labeling of the two nerves, or proximal/distal regions of the nerves, with fluorescent dyes was used to investigate topographic organization of sensory afferents in the honeybee. The sensory neurons of ampullaceal sensilla responsive to CO2, coelocapitular sensilla responsive to hygrosensory, and thermosensory stimuli and coeloconic sensilla of unknown function were characterized with large somata and supplied thick axons exclusively to the ventral nerve. Correspondingly, all glomeruli innervated by sensory tract (T) 4 received thick axonal processes exclusively from the ventral nerve. Almost all T1-3 glomeruli received a similar number of sensory afferents from the two nerves. In the macroglomerular complexes of the drone, termination fields of afferents from the two nerves almost completely overlapped; this differs from moths and cockroaches, which show heterogeneous terminations in the glomerular complex. In T1-3 glomeruli, sensory neurons originating from more distal flagellar segments tended to terminate within the inner regions of the cortical layer. These results suggest that some degree of somatotopic organization of sensory afferents exist in T1-3 glomeruli, and part of T4 glomeruli serve for processing of hygro- and thermosensory signals.

Sexual dimorphism in the antennal lobe of the ant Camponotus japonicus.

The carpenter ant, a social hymenopteran, has a highly elaborated antennal chemosensory system that is used for chemical communication in social life. The glomeruli in the antennal lobe are the first relay stations where sensory neurons synapse onto interneurons. The system is functionally and structurally similar to the olfactory bulbs of vertebrates. Using three-dimensional reconstruction of glomeruli and subsequent morphometric analyses, we found sexual dimorphism of the antennal lobe glomeruli in carpenter ants, Camponotus japonicus. Female workers and unmated queens had about 430 glomeruli, the highest number reported so far in ants. Males had a sexually dimorphic macroglomerulus and about 215 ordinary glomeruli. This appeared to result from a greatly reduced number of glomeruli in the postero-medial region of the antennal lobe compared with that in females. On the other hand, sexually isomorphic glomeruli were identifiable in the dorsal region of the antennal lobe. For example, large, uniquely shaped glomeruli located at the dorso-central margin of the antennal lobe were detected in all society members. The great sexual dimorphism seen in the ordinary glomeruli of the antennal lobe may reflect gender-specific tasks in chemical communications rather than different reproductive roles.

Serotonin-immunoreactive neurons in the antennal sensory system of the brain in the carpenter ant, Camponotus japonicus.

Social Hymenoptera such as ants or honeybees are known for their extensive behavioral repertories and plasticity. Neurons containing biogenic amines appear to play a major role in controlling behavioral plasticity in these insects. Here we describe the morphology of prominent serotonin-immunoreactive neurons of the antennal sensory system in the brain of an ant, Camponotus japonicus. Immunoreactive fibers were distributed throughout the brain and the subesophageal ganglion (SOG). The complete profile of a calycal input neuron was identified. The soma and dendritic elements are contralaterally located in the lateral protocerebrum. The neuron supplies varicose axon terminals in the lip regions of the calyces of the mushroom body, axon collaterals in the basal ring but not in the collar region, and other axon terminals ipsilaterally in the lateral protocerebrum. A giant neuron innervating the antennal lobe has varicose axon terminals in most of 300 glomeruli in the ventral region of the antennal lobe (AL) and a thick neurite that spans the entire SOG and continues towards the thoracic ganglia. However, neither a soma nor a dendritic element of this neuron was found in the brain or the SOG. A deutocerebral projection neuron has a soma in the lateral cell-body group of the AL, neuronal branches at most of the 12 glomeruli in the dorsocentral region of the ipsilateral AL, and varicose terminal arborizations in both hemispheres of the protocerebrum. Based on the present results, tentative subdivisions in neuropils related to the antennal sensory system of the ant brain are discussed.

Dual, multilayered somatosensory maps formed by antennal tactile and contact chemosensory afferents in an insect brain.

The antennae of most insects move actively and detect the physical and chemical composition of objects encountered by using their associated tactile sensors. Positional information is required for these sensory modalities to interpret the physical environment. Although we have a good understanding of antennal olfactory pathways, little is known about the destinations of antennal mechanosensory and contact chemosensory (gustatory) receptor neurons in the central nervous system. The cockroach Periplaneta is equipped with a pair of long, thin antennae, which are covered in bristles. The distal portions of each antenna possess about 6,500 bimodal bristles that house one tactile sensory and one to four contact chemosensory neurons. In this study, we investigated the morphologies of bimodal bristle receptor afferents by staining individual or populations of bristles. Unlike olfactory afferents, which project exclusively into the glomeruli in the ventral region of the deutocerebrum, both the presumptive mechanosensory and the contact chemosensory afferents projected into the posterior dorsal region of the deutocerebrum and the anterior region of the subesophageal ganglion. Each afferent showed multilayered segmentation and spatial occupation reflecting its three-dimensional position in the periphery. Presumptive contact chemosensory afferents, characterized by their thin axons and unique branching pattern, occupied more medioventral positions compared with the presumptive tactile afferents. Furthermore, projection fields of presumptive contact chemosensory afferents from single sensilla tended to be segregated from each other. These observations suggest that touch and taste positional information from the antenna is precisely represented in primary centers in a modality-specific manner.

Projection neurons originating from thermo- and hygrosensory glomeruli in the antennal lobe of the cockroach.

Most insects are equipped with specialized thermo- and hygroreceptors to locate a permissible range of ambient temperature and distant water sources, respectively. In the cockroach, Periplaneta americana, cold, moist, and dry receptor cells in the antennae send axons to particular sets of two or three glomeruli in the dorsocentral part of the antennal lobe (primary olfactory center), designated DC1-3 glomeruli. However, it is not known how thermo- and hygrosensory signals from these glomeruli are represented in higher-order centers, the protocerebrum, in any insect species. With the use of intracellular recording and staining techniques, we identified a new class of interneurons with dendrites almost exclusively in the DC1, DC2, or DC3 glomeruli and axons projecting to the protocerebrum in the cockroach. Remarkably, terminals of all these projection neurons (PNs) covered almost identical areas in the lateral protocerebrum (LP), although their termination areas outside the LP differed from neuron to neuron. The termination areas within the LP were distinct from, but close to, those of uniglomerular and macroglomerular PNs that transmitted signals concerning general odors and female sex pheromones, respectively. PNs originating from DC1, DC2, and DC3 glomeruli exhibited excitatory responses to cold, moist, and dry stimuli, respectively, probably due to excitatory synaptic input from cold, moist, and dry receptor cells, respectively, whereas their responses were often modulated by olfactory stimuli. These findings suggested that dorsocentral PNs participate in neural pathways that lead to behavioral responses to temperature or humidity changes.

Mutagenic activity and mutational specificity of antiprotozoal drugs with and without nitrite treatment.

We examined the mutagenic activities of six antiprotozoal drugs (three diaminopyrimidine compounds [pyrimethamine, diaveridine, and trimethoprim] and three 8-aminoquinoline derivatives [primaquine, pentaquine, and pamaquine]) in Escherichia coli WP2uvrA/pKM101 and Salmonella typhimurium TA100 and TA98 with and without nitrite treatment. The diaminopyrimidine compounds showed no mutagenic activity under any condition in any strain. The 8-aminoquinoline derivatives after nitrite treatment at 5-20 mM for 5 min at pH 3, on the contrary, showed clear mutagenicity in TA100 and WP2uvrA/pKM101 in the presence and absence of S9 mix. We concluded that 8-aminoquinoline derivatives became mutagenic following nitrite treatment. In the Lac(+) reversion assay with E. coli WP3101P-WP3106P, these nitrite-treated compounds induced G:C --> A:T transitions and G:C --> T:A transversions in the absence of S9 mix. On the other hand, A:T --> T:A transversions were induced only in the presence of S9 mix, suggesting a different kind of products may be responsible for the mutagenicity.