Superregular grammars do not provide additional explanatory power but allow for a compact analysis of animal song.

A pervasive belief with regard to the differences between human language and animal vocal sequences (song) is that they belong to different classes of computational complexity, with animal song belonging to regular languages, whereas human language is superregular. This argument, however, lacks empirical evidence since superregular analyses of animal song are understudied. The goal of this paper is to perform a superregular analysis of animal song, using data from gibbons as a case study, and demonstrate that a superregular analysis can be effectively used with non-human data. A key finding is that a superregular analysis does not increase explanatory power but rather provides for compact analysis: fewer grammatical rules are necessary once superregularity is allowed. This pattern is analogous to a previous computational analysis of human language, and accordingly, the null hypothesis, that human language and animal song are governed by the same type of grammatical systems, cannot be rejected.

Possible involvement of supersensitivity in cerebral ?-adrenergic and dopaminergic receptors in the occurrence of sensitization to d-methamphetamine in mice.

Behavioral sensitization of mice (male STD-ddy) to d-methamphetamine (MAP) and its correlation with the neurochemical alterations in cerebral catecholaminergic systems were investigated following the repeated administration of MAP (5 mg/kg, i.p. x 2/day, 5 days). MAP-pretreated mice showed an enhancement in MAP-stimulated locomotor activity following the readministration of MAP (0.625 mg/kg). The metabolic turnovers of cerebral norepinephrine (NE) and dopamine (DA) showed a significant decrease in these sensitized mice. The activities of tyrosine hydroxylase. DOPA decarboxylase, monoamine oxidase and catechol-O-methyltransferase, however, showed no change under the same experimental conditions. On the other hand, the repeated MAP pretreatment induced the enhancement of the specific bindings of [(3)H]dihydroalprenolol and [(3)H]spiperone to cerebral synaptic membrane, which resulted from the increase of B(max) values. Furthermore, pretreatments of mice with propranolol (10 mg/kg) and haloperidol (0.1 mg/kg) inhibited the development of behavioral sensitization to MAP. These results suggest that the supersensitivity in cerebral ?-adrenergic and dopaminergic receptors may be involved in behavioral sensitization to MAP.

Opposite effects of increased intracellular cyclic AMP on the heat and bradykinin responses of canine visceral polymodal receptors in vitro.

To clarify the validity of the long standing hypothesis that effects of E series prostaglandin (PG)S are mediated by cyclic AMP (cAMP), we studied the effects of increases in intracellular cAMP on the heat and bradykinin responses of testicular polymodal receptors. Polymodal receptor activities were recorded in vitro from testis-spermatic nerve preparations excised from dogs anesthetized with pentobarbital (30 mg/kg, i.v.). Increases in intracellular cAMP induced by either forskolin (5 or 10 microM), an adenylyl cyclase activator, or a mixture of dibutyryl cAMP (20-100 microM), a membrane permeable cAMP analog, and 3-isobutyl-1-methyl xanthine (20-100 microM), an inhibitor of the cAMP degrading enzyme, significantly augmented the response to heat (42-48 degrees C). In contrast, these substances failed to facilitate the response to bradykinin (0.1 or 1 microM) and instead suppressed it. Dideoxyforskolin (10 microM), an inactive analog of forskolin, had no effects on both the heat and bradykinin responses. These results demonstrate that an increase in intracellular cAMP induces opposite effects on the heat and bradykinin responses. Possible involvement of intracellular cAMP in the facilitatory effects of PGE2 on both responses was discussed in connection with the PGE receptor subtypes involved in the sensitization of the bradykinin and heat responses.

Possible contribution of protein kinase C in the effects of histamine on the visceral nociceptor activities in vitro.

To clarify the possible contribution of protein kinase C activation in histamine-induced excitation and sensitization of the heat response of testicular polymodal receptors, the effects of staurosporine, a protein kinase C inhibitor, and phorbol 12,13-dibutyrate, a protein kinase C activating phorbol ester, were studied in visceral polymodal receptors. Single polymodal receptor activities were recorded in vitro from testis-spermatic nerve preparations obtained from deeply anesthetized dogs (pentobarbital sodium, 30 mg/kg, i.v.). Histamine (10 microM)-induced excitation and facilitation of the heat response of polymodal receptors were both suppressed by staurosporine (1 microM), suggesting that activation of protein kinase C is involved in both these effects of histamine. Application of phorbol 12,13-dibutyrate (0.1 microM) mixed with histamine increased the histamine-induced excitation, whereas a 5 min application of phorbol 12,13-dibutyrate before histamine suppressed it. These results suggest that phorbol 12,13-dibutyrate-activated protein kinase C has inactivation as well as activation effects on the intracellular cascade connected to histamine receptors, and that the former has a slower time course.

Involvement of EP3 subtype of prostaglandin E receptors in PGE2-induced enhancement of the bradykinin response of nociceptors.

Prostaglandin E2 augments bradykinin-induced discharges of polymodal receptors as studied in vitro preparations. The antagonist and agonists for three subtypes of EP receptors were used to determine which subtype is involved in this phenomenon. The agonist for EP3 (M&B28767) simulated the PGE2-induced effect but not for EP2 (butaprost). The antagonist for EP1 (AH6809) did not suppress the effect. These findings indicate the involvement of the EP3 receptor subtype in the effect.

Muscarinic receptor-mediated regulation of OM-853-enhanced dopamine release in striatum of rat.

The effect of OM-853, a new vincamine analogue, on cerebral dopaminergic neurons was investigated in male Wistar rats. The administration of OM-853 (200 mg/kg p.o.) induced facilitation of the metabolic turnover of dopamine (DA) in all brain areas except the cerebral cortex. Addition of OM-853 enhanced the release of [3H]DA from striatal slices; this release was antagonized by atropine (10(-7) M). However, pretreatment with scopolamine (0.5 mg/kg s.c.) inhibited the enhancement of striatal DA turnover induced by OM-853 administration. OM-853 (10(-4) M) inhibited [3H]quinuclidinyl benzilate binding to muscarinic cholinergic receptors in a striatal particulate fraction more potently than carbachol (10(-4) M). These results suggest that OM-853 may induce facilitation of striatal DA turnover by enhancing DA release via the stimulation of muscarinic cholinergic receptor.

Essential IgG cryoglobulinemia with purpura and cold urticaria.

An 80-year-old woman with essential cryoglobulinemia developed recurrent, widespread, purpuric lesions with superficial skin ulcers and cold urticaria. No disorders of other organ systems were recognized. Attempts to transfer the cold sensitivity passively by serum and isolated cryoprecipitate of the patient were successful. Immunochemical studies showed that the cryoglobulin was composed of IgG only. It was suggested that the cryoprecipitate might not be due to immune complex formation in this case.

Potentiation and suppression of the histamine response by raising and lowering the temperature in canine visceral polymodal receptors in vitro.

It is well known that itch and inflammatory pain are enhanced when tissue is warmed, while they are suppressed when tissue is cooled. To see whether these changed sensations are based on the changed response of sensory receptors, the temperature dependency of the excitation of polymodal receptors induced by histamine, which plays an important role both in itch and inflammatory pain, was studied. Single nerve activities of polymodal receptors were recorded from canine testis-spermatic nerve preparations in vitro. Raising the temperature from 34 to 40 degrees C, a temperature below the threshold for the heat response of polymodal receptors, facilitated the histamine-induced nerve discharge to 268% of that at 34 degrees C, while lowering the temperature to 28 degrees C decreased it to 25%. Facilitation of the histamine response was also observed in the noxious temperature range (48 and 51 degrees C). These results suggest that the potentiation of the histamine-induced sensation by increasing the tissue temperature, as well as its suppression by lowering tissue temperature, can be explained by a temperature-dependent response of peripheral sensory receptors to histamine. However, the suppression of itch by noxious heat reported by Bickford (Bickford, R.G., Experiments relating to the itch sensation, its peripheral mechanism, and central pathways, Clin. Sci. Incorp. Heart, 3 (1937) 377-386) cannot be explained by the noxious heat-induced facilitation of the peripheral receptor response reported in this paper.

Possible involvement of the EP2 receptor subtype in PGE2-induced enhancement of the heat response of nociceptors.

Prostaglandin E2 augments bradykinin- and heat-induced discharges of polymodal receptors as studied in vitro preparations. Our previous study revealed the involvement of the EP3 receptor subtype in the PGE2 induced enhancement of the BK response [Brain Res. 632 (1993) 321-324]. The agonist for EP2 (butaprost; 10(-8) M) significantly augmented heat responses, but did not augment the BK responses at concentrations from 10(-8) to 10(-5) M; however, the agonist for EP3 (M&B28767) or EP1 (17-phenyl-trinor-PGE2) at 10(-7) M did not affect the heat responses. These findings indicate the involvement of the EP2 receptor subtype in the augmenting effect of PGE2 on heat responses.

Augmenting effects of cyclic AMP on the heat response of canine testicular polymodal receptors.

It has long been thought that the augmenting effects of E series prostaglandins (PG) are mediated by cyclic AMP (cAMP). In clarifying the validity of this hypothesis, we studied the effects of increases in intracellular cAMP on the heat response of testicular polymodal receptors. Recordings were obtained from testis-spermatic nerve preparations excised from dogs anesthetized with pentobarbital (30 mg/kg, i.v.). Induction of increases in intracellular cAMP by either forskolin, an adenylyl cyclase activator, or a mixture of dibutyryl cAMP (10(-4) M) and 3-isobutyl-1-methyl xanthine (10(-4) M) significantly and reversibly augmented the heat response. These results support the notion that cAMP is involved in the augmenting effect of PG E2 on the heat response of nociceptors.

Evidence that protein kinase C activation is involved in the excitatory and facilitatory effects of bradykinin on canine visceral nociceptors in vitro.

The involvement of protein kinase (PK) C activation in the effects of bradykinin (BK) on peripheral nociceptors, polymodal receptors, was examined using canine testis-spermatic nerve preparations in vitro. Phorbol 12,13-dibutyrate 0.1 microM, which activates PKC, suppressed the BK-induced excitation when applied for 3-5 min prior to BK application, but facilitated it when applied simultaneously with BK. Neither effect was induced by an inactive phorbol ester, 4alpha-phorbol 12, 13-didecanoate, demonstrating that both effects were mediated through the activation of PKC. In addition, staurosporine 1 microM, a PK inhibitor, suppressed both BK-induced excitation and facilitation of the heat response of testicular polymodal receptors without influencing on-going activities and the heat response itself. These results suggest that PKC activation is involved in the excitatory and facilitatory effects of BK on peripheral nociceptors.

Histamine-induced sensitization of the heat response of canine visceral polymodal receptors.

In elucidating the possible involvement of histamine (His) in hyperalgesia to heat, the effects of His on the heat response of testicular polymodal receptors were studied in vitro in canine testis-spermatic nerve preparations. His (100 and 1000 microM) induced discharges > 0.5 impulses/s (high-responders) in about one third of units tested. His (> or = 10 microM) facilitated the heat response irrespective of whether His alone induced substantial excitation, and the magnitude of facilitation at 100 microM did not differ between high- and low-responders (His-induced discharges < or = 0.5 impulses/s). Conduction velocity of high-responders at 100 microM (2.2 +/- 0.9 m/s, n = 5) was slower on average than that of low-responders (12.9 +/- 1.6 m/s, n = 9). The sensitizing effect of His reported in this paper suggests that His plays a role in hyperalgesia.

Forskolin does not augment the bradykinin response of canine visceral polymodal receptors in vitro.

In clarifying the possible involvement of cyclic AMP (cAMP) in prostaglandin (PG) E2-induced sensitization of the bradykinin response of canine testicular polymodal receptors, the effects of forskolin, an activator of adenylyl cyclase, were studied in the presence and absence of acetylsalicylic acid (ASA, 550 microM) which blocks PG production. Forskolin (10 microM) seldom induced discharges in polymodal receptors. An unexpected outcome of this study was that forskolin induced no facilitation of the bradykinin (0.1 microM) response, both in the absence and presence of ASA. A slight yet significant suppression of the bradykinin response was instead observed in the absence of ASA. These results suggest that intracellular cAMP may be related with PG E2-induced sensitization of the bradykinin response through its decrease.

Excitation and sensitization of the heat response induced by a phorbol ester in canine visceral polymodal receptors studied in vitro.

To clarify the possible involvement of protein kinase (PK) C activation in the excitation and sensitization of polymodal receptors (PMRs), the effects of phorbol 12,13-dibutyrate (PDBu) on PMRs were studied in canine testis-spermatic nerve preparations in vitro. Application of PDBu (10(-7), 10(-6), AND 10(-5) M) for 5 min evoked a significant increase in the ongoing activity of the PMRs within 15 min. PDBu (10(-8) to 10(-5) M) significantly augmented the subsequent heat responses of the PMRs. Staurosporine (10(-6) M), a PK inhibitor, attenuated the effect of PDBu on heat responses. These data suggest that activation of PKC contributes to the activities of PMRs.

Synthesis and antimicrobial activity of cephalosporins with a 1-pyridinium substituent carrying a 5-membered heterocycle at the C-3 position.

A series of potent antimicrobial agents have been prepared. These derivatives are cephalosporins carrying a pyridine ring substituted with a heterocycle in the C-3 position. Some of them showed excellent activity not only against Gram-negative organisms including Pseudomonas aeruginosa but also against Gram-positive ones. In view of their biological and physico-chemical properties, 7 beta-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[4-(2 or 5-oxazolyl)-1-pyridinium]methyl-3-cephem-4-carboxylate 8f (DQ-2522) and 8g (DQ-2556) were chosen as candidates for further evaluation.

Construction of rat-mouse T-cell hybridomas that constitutively produce rat IL-2.

We have established rat-mouse T-cell hybridomas that constitutively produce rat Interleukin-2 (IL-2). T-cell hybridomas cannot be boosted to a higher level of IL-2 production by Con A stimulation. IL-2 prepared from T-cell hybridomas and from Con A activated rat spleen cells was partially purified using Ultrogel AcA 54 chromatography and ion exchange chromatography on Mono Q or chromatofocusing on Mono P. When analyzed on Mono P, IL-2 activity derived from IA2-B10 T-cell hybridoma eluted as a single peak with pH range 6.9-7.1, whereas IL-2 derived from Con A activated spleen cells resolved into four peaks within the following pH range: 7.1-7.2, 6.5-6.6, 6.1-6.2, and 5.6-5.7. Neuraminidase-treated IL-2 derived from Con A activated spleen cells resolved into single peaks appearing in the pH range 7.1-7.2. In contrast, neuraminidase treatment did not change the elution profile of IL-2 derived from the IA2-B10 hybridoma. IL-2 activity derived from the 3D6-B1 T-cell hybridoma also eluted as a single peak with the pH range 7.1-7.2. Neuraminidase treatment did not change the elution profile of IL-2. These data demonstrate that heterogeneity of IL-2 might be due to differences in the degree of glycosylation of IL-2 and differences in the sources of T-cells from which the IL-2 has derived.

Youngsters do not pay attention to conversational rules: is this so for nonhuman primates?

The potentiality to find precursors of human language in nonhuman primates is questioned because of differences related to the genetic determinism of human and nonhuman primate acoustic structures. Limiting the debate to production and acoustic plasticity might have led to underestimating parallels between human and nonhuman primates. Adult-young differences concerning vocal usage have been reported in various primate species. A key feature of language is the ability to converse, respecting turn-taking rules. Turn-taking structures some nonhuman primates' adult vocal exchanges, but the development and the cognitive relevancy of this rule have never been investigated in monkeys. Our observations of Campbell's monkeys' spontaneous vocal utterances revealed that juveniles broke the turn-taking rule more often than did experienced adults. Only adults displayed different levels of interest when hearing playbacks of vocal exchanges respecting or not the turn-taking rule. This study strengthens parallels between human conversations and nonhuman primate vocal exchanges.