Safety and factors contributing to the difficulty of laparoscopic surgery for rectal cancer treated with preoperative chemoradiotherapy.

BACKGROUND: The safety of laparoscopic surgery for rectal cancer following chemoradiotherapy (CRT) has not been fully established. The aim of our retrospective study was to examine the outcomes and the factors contributing to the difficulty of laparoscopic surgery after CRT. METHODS: Eighty-seven consecutive rectal cancer patients treated with CRT were analyzed. Clinicopathological factors were compared between laparoscopic surgery (n = 57) and open surgery (n = 30) groups, and factors that correlated with operation time and blood loss were analyzed in low anterior resection (LAR) cases in the laparoscopic surgery group (n = 46). RESULTS: There was less blood loss in the laparoscopic surgery group than in the open surgery group (191 vs. 1,043 ml, p = 0.0001), and the operation time in the two groups was similar (329 vs. 322 min, p = 0.8). The rate of conversion from laparoscopic surgery to open surgery was 1.8 %. There was no significant difference in the morbidity rate (laparoscopic surgery 22.8 % vs. open surgery 33.3 %, p = 0.3). All circumferential resection margins were clear. Three-year cumulative rates of local recurrence were as follows: laparoscopic surgery: 1.9 % vs. open surgery: 8.4 % (p = 0.4), and distant recurrence was 28.5 % in laparoscopic surgery vs. 22.7 % in open surgery (p = 0.8) and these rates were not significantly different. In laparoscopic LAR cases, a shorter distance of the tumor from the anal verge was associated with a longer operation time. A high computed tomography Hounsfield units value of the mesorectum (CTV) was associated with increased blood loss in the first 23 cases, but not in the other 23 cases. CONCLUSIONS: Laparoscopic surgery following CRT was safe and feasible. A shorter anal verge was associated with a longer operation time. Blood loss increased in cases with high CTV, but this can likely be mitigated by experience.

Two cases of diverticulitis in patients with Williams syndrome.

Williams syndrome is rare and associated with physical anomalies and mental retardation. It is a disease resulting from a gene deletion of chromosome 7. The main concurrent medical conditions typically associated with Williams syndrome are heart defects such as supravalvular aortic stenosis, mental retardation, and unusual physical characteristics. It is also associated with colon diverticulosis and diverticulitis. In the present article, we report on 2 cases of diverticulitis in patients with Williams syndrome, in whom surgery was performed. In many cases of diverticulitis in patients with Williams syndrome, surgical treatment is indicated. It is important to take diverticulitis into consideration when examining a patient with Williams syndrome presenting with abdominal pain and consider surgical treatment if necessary.

A case of fulminant amebic colitis with multiple large intestinal perforations.

Amebic colitis normally causes mucous and bloody diarrhea stool as predominant symptoms, thus leading to a course of chronic colitis. However, though rare, there exists a fulminating type that causes intestinal perforations due to wide necrosis of the large intestine. We encountered a case of fulminant amebic colitis that lead to death due to multiple large intestinal perforations. The patient was a 72-year-old female. The patient was admitted to our hospital with symptoms of fever, abdominal pain, and diarrhea. She continued to have a fever of over 38 degrees C and increased left abdominal pain. An abdominal computed tomography scan revealed free gas on the abdominal side of the kidney. Therefore, gastrointestinal perforations were diagnosed and surgery was performed. In surgery, many perforated parts were observed from the appendix to the descending colon, and subtotal colectomy was performed. However, sepsis and disseminated intravascular coagulation occurred, and the patient died on the eighth postoperative day.

Treatment with edaravone improves the survival rate in renal warm ischemia-reperfusion injury using rat model.

Renal ischemia-reperfusion (I/R) injury during renal transplantation is a significant cause of renal dysfunction. The pathological role of free radicals in this process is a major concern. We investigated the effect of a free radical scavenger, edaravone (MCI-186), in renal I/R injury. Male Lewis rats (270 to 320 g) were used for the model. The right kidney was harvested and left renal artery and vein were clamped as laparotomy. The kidney was reperfused after 90 minutes of ischemia. Edaravone (10 mg/kg) was delivered intravenously before ischemia and after reperfusion to prevent the neutrophil activation. In the nontreatment I/R group, no rat survived beyond 4 days. However, in the edaravone I/R treatment group, one among five rats survived more than 7 days. These results suggested that treatment with edaravone ameliorated renal I/R injury, and that the agent has the potential to ameliorate preservation injury in renal transplantation.

Benefical effect of neutrophil elastase inhibitor on renal warm ischemia-reperfusion injury in the rat.

Renal ischemia-reperfusion (I/R) injury is a significant problem in renal transplantation. Neutrophils play an important role in renal I/R injury. Several reports have demonstrated that neutrophil elastase derived from the activated neutrophils might play an important role in this injury. We investigated the effect of a neutrophil elastase inhibitor in renal I/R injury. Male Lewis rats (270-320 g) were used in the model. The right kidney was harvested and the left renal artery and vein were clamped at laparotomy. The kidney was reperfused after 90 minutes of ischemia. Neutrophil elastase inhibitor (ONO-5046: 30 mg/kg) was delivered intravenously before ischemia and after reperfusion to prevent neutrophil activation. In the nontreatment I/R group, no hosts survived 4 days. However, after treatment with neutrophil elastase inhibitor, 3 of 10 rats in the I/R group, survived more than 7 days. These results demonstrated that treatment with neutrophil elastase inhibitor ameliorated renal I/R injury.

Ia-restricted interaction of normal lymphoid cells and SJL lymphoma (reticulum cell sarcoma) leading to lymphokine production. III. Relative roles of reticulum cell sarcoma and normal lymphoid cells in lymphokine production.

Production of interleukin 2 (IL-2) in mixed lymphocyte cultures of SJL/J lymph node (LN) and gamma-irradiated, syngeneic lymphoma cells of transplantable reticulum cell sarcoma (gamma-RCS) was abolished by pactamycin pretreatment of gamma-RCS. LN cells needed for this interaction were Lyt-2 T-cells, not adherent to Sephadex G-10. The effect of separation of T-cells and gamma-RCS after the first 24 hours of culture suggested that both components contributed to the IL-2 production. Exogenous IL-2, but not interleukin 1 (IL-1), restored the ability of pactamycin-treated gamma-RCS to induce syngeneic T-cell proliferation. The inability of T-cells from "nonresponder" F1 hybrids of SJL to proliferate to gamma-RCS was not corrected by addition of IL-1 or IL-2. Interferon (IFN) production also required the presence of untreated gamma-RCS and LN cells, but it was dependent on a Sephadex G-10 and plastic adherent cell in LN. IFN-free supernatant of LN cells plus gamma-RCS induced IFN production in fresh normal lymphoid cells, suggesting a possible indirect induction of this lymphokine. In addition, unirradiated RCS cells (la+ cells) produced immune IFN over a period of 3 weeks in vitro, after which the cells lost their viability. Prolonged IL-2 production was not observed in these cultures. The possible biological importance of the lymphokine production during the exaggerated syngeneic mixed lymphocyte reactions induced by RCS cells is discussed.

Ia-restricted interaction of normal lymphoid cells and SJL lymphoma (reticulum cell sarcoma) leading to lymphokine production. II. Rapid production of antibody-enhancing factor, interleukin 2, and immune interferon.

Mixed cell cultures of syngeneic lymph node (LN), spleen, or thymus and gamma-irradiated, syngeneic lymphoma cells of transplantable reticulum cell sarcomas (gamma-RCS) produced within 24 hours high titers of interleukin 2 (IL-2) and immune interferon in their supernatant (SN). These lymphokine titers were much higher than those seen after stimulation with allogeneic cells. SN also had marked enhancing activity for antibody production by anti-T-cell serum plus complement-treated spleen cells to trinitrophenylated polyacrylamide in vitro. This activity could be removed by absorption with cells of an IL-2-dependent cytotoxic cell line. Mixtures of gamma-RCS and LN cells from SJL/J F1 hybrid mice produced these lymphokines only when the non-SJL parent contributed H-2s or H-2b, but not H-2k or H-2d, in the I-region. These I-region restrictions were similar to those observed previously with respect to the ability of T-cells from SJL F1 hybrids to give proliferative responses to gamma-RCS in vitro and of these mice to support tumor growth in vivo. gamma-RCS also induced rapid interferon production in vivo, but serum titers 24 hours after injection consisted primarily of interferon resistant to pH 2 and neutralized by antibody to virally induced interferon (IFN-alpha/beta), and the production of IFN-alpha/beta was not subject to the same genetic restrictions. Although reticulum cell sarcoma cell extracts had no detectable effect in vitro, they were capable of inducing transient IFN production in vivo.

Hemodynamic effects of dexmedetomidine in patients after cardiac surgery.

AIM: Dexmedetomidine hydrochloride (Prece-dex(R)) is a potent and highly selective central a2-adrenoreceptor agonist. Dexmedetomidine has recently been approved as a new sedative drug, however, its hemodynamic effects on patients just after cardiac surgery has not been established. METHODS: Nineteen patients (14 males and 5 females) who underwent elective cardiovascular surgery were included in this study. The mean age of the patients was 65 years. Coronary artery bypass grafting was performed in 8 patients, aortic valve surgery in 5, mitral valve plus radiofrequency Maze surgery in 3, graft replacement of the ascending aorta in 2 and double valve replacement in 1. After surgery, dexmedetomidine was continuously infused for 3 h in total at a rate of 0.8 mg/kg/h for the initial 1 h and followed by 0.4 mg/kg/h. RESULTS: All patients were well sedated during dexmedetomidine infusion. Dexmedetomidine infusion induced a decrease in systemic blood pressure and systemic vascular resistance index. Heart rate, stroke index, central venous pressure, pulmonary artery pressure and pulmonary artery resistance index remained unchanged. Mixed venous oxygen saturation significantly decreased and arterio-venous O2 content difference increased after the beginning of dexmedetomidine infusion. CONCLUSIONS: Continuous dexmedetomidine infusion did not influence the hemodynamic condition except for the vaso-dilating effect, thus dexmedetomidine was considered to be a viable sedative drug after cardiac surgery.

Granulocyte-macrophage colony-stimulating activity in the serum of estriol-treated mice.

Granulocyte-macrophage colony-stimulating activity (GM-CSA) in mouse serum was examined after a single intraperitoneal injection with 10 mg estriol (E3). GM-CSA was detectable as early as 6 h after E3 administration and reached a peak by 24 h. Elevation of GM-CSA in the serum was maintained for at least 30 days. Using 0.1-10 mg of E3 there was a dose-dependent increase in serum GM-CSA when tested 24 h after E3 treatment. The majority of GM-CSA was adsorbed onto Concanavalin A-Sepharose 4B and was eluted by 0.2 M methyl-alpha-D-mannopyranoside, suggesting its glycoprotein nature. When E3-treated mouse serum was applied onto Sephacryl S-300 without any pretreatment, GM-CSA was detected as a sharp single peak with an apparent molecular weight of 440,000 daltons. When GM-CSA was treated with neuraminidase, however, and then applied to Sepharose CL-6B under disaggregating conditions (6 M guanidine HCl), the minimum molecular weight of the active component was estimated as 13,000 daltons.

Effects of estrogen on hepatic hemopoiesis in the adult mouse.

After a single pharmacologic dose of estriol (E3) treatment, an increase in number of focal areas of hepatic hemopoiesis was observed in adult mice. When syngeneic bone marrow cells were transfused into E3-treated mice, focal hepatic hemopoiesis was increased further. In a single experiment, using a single cell suspension, the concentration of CFUs in the liver was increased 5 days after E3-treatment, while that in the blood decreased. In addition, 51Cr-labeled bone marrow cells selectively accumulated in the E3-treated mouse liver. These results suggest, but in not sense prove, that circulating hemopoietic stem cells are trapped in the E3-treated mouse liver, and that E3-activated Kupffer cells may play a central role in focal hemopoiesis in the liver.

Lobule structure and somatotopic organization of the medullary facial lobe in the channel catfish Ictalurus punctatus.

Correlation of the somatotopic organization of the facial lobe (FL), a primary medullary gustatory nucleus in the channel catfish Ictalurus punctatus, with its lobular substructure was investigated to examine a possible structural basis for the excellent ability of ictalurid catfishes to localize a food source in the environment. The FL in the channel catfish is composed of six longitudinal columns (i.e., lobules) extending rostrocaudally and differing from each other in their length and location within the lobe. Each lobule receives segregated input from discrete portions of the external body surface. The three more medial lobules in the FL receive input (from medial to lateral) from the medial mandibular barbel, the lateral mandibular barbel, and the maxillary barbel, respectively. The proximal-distal axis of each of the barbels is represented in a posteroanterior lobule axis. The largest lobule, the face-flank lobule, is located dorsolaterally in the FL, whereas the anteroposterior body axis is represented in the posteroanterior lobule axis. This indicates that the neural representation of the external body surface of the channel catfish faces caudally in the FL. The two shortest lobules, positioned ventral to the face-flank lobule, receive input from the nasal barbel and the pectoral fin, respectively. The rostrocaudal dimensions of each of the barbel lobules correlate well with the relative lengths of the barbels. Taste-sensitive portions within the three barbel lobules examined were generally confined to the dorsal region, whereas tactile responses were observed throughout the lobules.2+ primarily tactile, zone.

Production of auto-anti-idiotypic antibody during the normal immune response. VI. Hapten augmentation of plaque formation and hapten-reversible inhibition of plaque formation as assays for anti-idiotype antibody.

(1) Evidence has been presented that the detection of hapten-augmentable plaques indicates cells whose secretion of antibody had been blocked by the binding of auto-anti-id to cell surface idiotypes. Because of the dependence of the assay on the affinities of the various species for one another, the number of hapten-augmentable plaques detected should be regarded as a minimal estimate of the number of cells whose secretion of antibody is inhibited by auto-anti-id. For confirmation that hapten-augmentable PFC are due to auto-anti-id 2 principal controls are important: (a) incubation of the spleen cell population with hapten prior to plaquing should remove the hapten-augmentable PFC; (b) the dialyzed supernate from hapten incubated cells should inhibit plaque formation in a hapten-reversible manner. (2) Evidence has been presented that hapten-reversible inhibition of plaque formation can serve as an assay for anti-id. Apparent false positive assays can result from the presence of anti-hapten antibody or antigen-antibody complexes; however, these apparent false positives are rarely reversed by hapten. Removal of anti-hapten antibody, by passage over an antigen immunoadsorbent, will eliminate this source of false positives and the procedure is recommended. False negative results can arise from mismatching of the anti-ids in the sample to be assayed and the idiotypes of the target cells used in the assay. This can result from shifts in idiotype expression related to age and time after antigen injection. False negatives can also result from the presence of idiotype-anti-id complexes in the sample to be assayed. This source of false negatives can sometimes be eliminated by passage of the sample through an antigen immunoadsorbent.

Increased soluble CD4 and decreased soluble CD8 molecules in patients with Sjögren's syndrome.

PURPOSE: A new enzyme-linked immunosorbent assay for soluble CD4 (sCD4) and soluble CD8 (sCD8) molecules has been developed. We estimated the concentrations of these molecules in patients with Sjögren's syndrome and in patients with systemic lupus erythematosus (SLE) serving as a control population for non-Sjögren's inflammatory disease, since several findings suggestive of an aberration of immunocompetent cells have been reported in these autoimmune diseases. PATIENTS AND METHODS: The study population consisted of 41 patients with Sjögren's syndrome (28 cases of the primary form and 13 cases of the secondary form), 66 patients with SLE, and 43 normal individuals. Serum samples and clinical and laboratory data were collected from each patient and control. Assays of the sCD4 and sCD8 molecules were performed using an enzyme-linked immunosorbent kit developed by T Cell Science Inc., Cambridge, MA. RESULTS: The concentration of sCD4 was significantly increased in patients with both primary and secondary Sjögren's syndrome as compared with that in the control subjects. In contrast, sCD8 was significantly decreased in patients with primary disease but not in patients with secondary disease. A low or high concentration of sCD8 was significantly correlated with the presence of anti-SS-A antibody or hypocomplementemia, respectively. A similar significant correlation was noted between an increased sCD4 concentration and increased serum IgG level. In patients with SLE, the levels of both sCD4 and sCD8 were significantly increased. CONCLUSION: These observations represent the first evidence of an increased level of the sCD4 molecule and a decreased level of the sCD8 molecule and an association with immunologic abnormalities in Sjögren's syndrome. The increased and decreased levels of these soluble molecules observed may play a pathologic role in patients with Sjögren's syndrome.

Marked reduction of mortality in salt-loaded Dahl salt-sensitive rats by the new, selective endothelin ETA receptor antagonist, J-105859.

OBJECTIVE: To examine the chronic effects of a newly synthesized, potent and selective endothelin (ET) ETA receptor antagonist, J-1 05859, on mortality in salt-loaded Dahl salt-sensitive (DS) rats and to confirm the potential of this compound as an ETA antagonist METHODS: Vehicle and J-105859 were administered to salt-loaded DS rats for 12 weeks. Throughout the experimental period, blood pressure was measured continuously using a telemetry system and the survival rate was determined. The surviving animals were subsequently sacrificed and autopsy was performed. Binding and functional assays were also carried out to characterize J-1 05859. RESULTS: The Ki values of J-1 05859 for cloned human ETA and ETB were 0.025 and 48 nmol/l, respectively. J-105859 inhibited ET-1-induced contractions in rabbit iliac artery (pA2 = 10.08) and BQ-3020 (ETB agonist)-induced contractions in pulmonary artery (pA2 = 7.63). The pressor response to intravenous (i.v.) ET-1 (0.5 nmol/kg) was significantly inhibited by J-1 05859 at a dose of 0.03 mg/kg i.v. Chronic treatment with J-1 05859 [0.1 and 1 mg/kg per day orally (p.o.)] from the prehypertensive stage decreased the mortality of salt-loaded DS rats and markedly inhibited the development of brain lesions. The survival rates in the control and J-1 05859 (0.1 and 1 mg/kg per day) groups were 34, 80 and 100%, respectively. Development of hypertension was markedly inhibited at a dose of 1 mg/kg per day. CONCLUSION: J-105859 is a selective, potent, orally active ETA-selective antagonist ETA antagonists may reduce morbidity as well as mortality in salt-sensitive hypertension.

Structure-activity relationships of cyclic pentapeptide endothelin A receptor antagonists.

Analogues of the natural product endothelin A (ETA) receptor antagonists cyclo(-D-Trp1-D-Glu2-Ala3-D-Val4-Leu5-) (1) and cyclo(-D-Trp1-D-Glu2-Ala3-D-alloIle4-Leu5-) (2) were prepared and tested for inhibitory activity against [125I]endothelin (ET-1) binding to protein ETA receptors. The DDLDL chirality sequence of the natural products appeared to be critical for inhibitory activity because conversion of either D-Trp or D-Glu (or both) in 1 to the corresponding L-isomer(s) abolished this property. Systematic modifications at each position of the natural products clarified the structure-activity relationships and led to highly potent and selective ETA receptor antagonists. Most replacements of D-Trp1 and Leu5 with other amino acids caused a significant loss of inhibitory activity. In contrast, replacement of D-Glu2 with D-Asp2 enhanced the activity. With regard to the Ala3 position, all analogues with imino acids, independent of being cyclic or acyclic, showed higher affinities than did the amino acid analogues. In addition, most replacements with amino acids, which had various functional groups in their side chains, did not significantly modify ETA binding affinity. The D-Val4/D-alloIle4 position was very important for inhibitory activity, and a beta-position branched D-amino acid or a D-heteroarylglycine was preferable at this position. Among synthesized cyclic pentapeptides, compound 36 (BQ-518) was the most potent ETA receptor antagonist, with a pA2 of 8.1 against ET-1-induced vasoconstriction in isolated porcine coronary arteries. This compound also showed the greatest selectivity between ETA and ETB receptors (IC50 for human ETA = 1.2 nM, IC50 for human ETB = 55 microM). In contrast, compound 8 (BQ-123) is a highly soluble, potent, and selective ETA receptor antagonist (pA2 = 7.4, IC50 for human ETA = 8.3 nM, IC50 for human ETB = 61 microM). The sodium salt of 8 is practically freely soluble in saline. These compounds are useful tools for not only in vitro but also in vivo pharmacological studies.

Structure-based generation of a new class of potent Cdk4 inhibitors: new de novo design strategy and library design.

As a first step in structure-based design of highly selective and potent Cdk4 inhibitors, we performed structure-based generation of a novel series of Cdk4 inhibitors. A Cdk4 homology model was constructed according to X-ray analysis of an activated form of Cdk2. Using this model, we applied a new de novo design strategy which combined the de novo design program LEGEND with our in-house structure selection supporting system SEEDS to generate new scaffold candidates. In this way, four classes of scaffold candidates including diarylurea were identified. By constructing diarylurea informer libraries based on the structural requirements of Cdk inhibitors in the ATP binding pocket of the Cdk4 model, we were able to identify a potent Cdk4 inhibitor N-(9-oxo-9H-fluoren-4-yl)-N'-pyridin-2-ylurea 15 (IC(50) = 0.10 microM), together with preliminary SAR. We performed a docking study between 15 and the Cdk4 model and selected a reasonable binding mode which is consistent with the SAR. Further modification based on the proposed binding mode provided a more potent compound, N-[(9bR)-5-oxo-2,3,5,9b-tetrahydro-1H-pyrrolo[2,1-a]isoindol-9-yl]-N'-pyridin-2-ylurea 26a (IC(50) = 0.042 microM), X-ray analysis of which was accomplished by the soaking method. The predicted binding mode of 15 in Cdk4 was validated by X-ray analysis of the Cdk2-26a complex.

A novel approach for the development of selective Cdk4 inhibitors: library design based on locations of Cdk4 specific amino acid residues.

Identification of a selective inhibitor for a particular protein kinase without inhibition of other kinases is critical for use as a biological tool or drug. However, this is very difficult because there are hundreds of homologous kinases and their kinase domains including the ATP binding pocket have a common folding pattern. To address this issue, we applied the following structure-based approach for designing selective Cdk4 inhibitors: (1) identification of specifically altered amino acid residues around the ATP binding pocket in Cdk4 by comparison of 390 representative kinases, (2) prediction of appropriate positions to introduce substituents in lead compounds based on the locations of the altered amino acid residues and the binding modes of lead compounds, and (3) library design to interact with the altered amino acid residues supported by de novo design programs. Accordingly, Asp99, Thr102, and Gln98 of Cdk4, which are located in the p16 binding region, were selected as first target residues for specific interactions with Cdk4. Subsequently, the 5-position of the pyrazole ring in the pyrazol-3-ylurea class of lead compound (2a) was predicted to be a suitable position to introduce substituents. We then designed a chemical library of pyrazol-3-ylurea substituted with alkylaminomethyl groups based on the output structures of de novo design programs. Thus we identified a highly selective and potent Cdk4 inhibitor, 15b, substituted with a 5-chloroindan-2-ylaminomethyl group. Compound 15b showed higher selectivity on Cdk4 over those on not only Cdk1/2 (780-fold/190-fold) but also many other kinases (>430-fold) that have been tested thus far. The structural basis for Cdk4 selective inhibition by 15b was analyzed by combining molecular modeling and the X-ray analysis of the Cdk4 mimic Cdk2-inhibitor complex. The results suggest that the hydrogen bond with the carboxyl group of Asp99 and hydrophobic van der Waals contact with the side chains of Thr102 and Gln98 are important. Compound 15b was found to cause cell cycle arrest of the Rb(+) cancer cell line in the G(1) phase, indicating that it is a good biological tool.

Anatomical location of a taste-related region in the thalamic reticular nucleus in rats.

To locate a taste-related region in the thalamic reticular nucleus (Rt), we explored a reticular region having connections with the thalamic taste relay and the cortical taste area (CTA), by neuronal tracing methods using HRP, WGA-HRP and biocytin. Tracer injections at the thalamic taste relay, i.e., the parvicellular part of the thalamic posteromedial ventral nucleus (VPMpc), labeled cell bodies and axon terminals in a confined portion of the ipsilateral Rt. This was located at the ventromedial-most portion of the nucleus at the level of approx. 1.2 mm rostral to the rostral end of the VPMpc. Tracer injections at the CTA ipsilaterally labeled axon terminals in the same region of the Rt, as did the thalamic injections. When WGA-HRP was injected at this taste-related region in the Rt, we observed labeled cell bodies in layer VI in the CTA; in the VPMpc we saw densely labeled axon terminals but few, if any, labeled cell bodies. The results indicated that the taste-related region in the Rt receives input from the VPMpc and CTA, and sends output to the VPMpc. They also showed that the reticulo-thalamic projections were much heavier than the thalamo-reticular ones in the taste system.

Somatotopical organization of the intermediate nucleus of the facial lobe in the channel catfish, Ictalurus punctatus.

Neurons in the intermediate nucleus of the facial lobe (nIF) in the channel catfish that respond to tactile stimulation of oral and/or extra-oral epithelia are somatotopically arranged. Neurons in rostrodorsal portions of the nIF responded to tactile stimulation or deflection of the ipsilateral barbels, whereas neurons arranged in a dorsoventral direction in caudoventral regions of the nIF had receptive fields on the ipsilateral lips and the oral cavity, respectively. Suppression of neuronal activity in response to tactile stimulation of the external skin and/or the oral cavity was indicated for some units. Taste responses were not observed.