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T Kambara

Publications and source records attributed to T Kambara.

At least 55 records · Page 3Linked to original sources
PubMed1996

Model of P- and T-electroreceptors of weakly electric fish.

To clarify the microscopic mechanisms by which P- and T-receptors encode amplitude modulation and zero crossing time of jamming signals, we present a model of P- and T-receptors based on their physiological and anatomical properties. The model consists of a receptor cell, supporting cells, and an afferent nerve fiber. The basal membrane of the receptor cell includes voltage-sensitive Ca2+ channels, Ca(2+)-activated K+ channels, and leak channels of Na+, K+, and Cl-. The driving force of potential change under stimulation is generated by the voltage-sensitive Ca2+ channels, and the suppressing force of the change is generated by Ca(2+)-activated K+ channels. It has been shown that in T-receptor cells the driving force is much stronger than the suppressing force, whereas in P-receptor cells the driving force is comparable with the suppressing force. The difference in various kinds of response properties between P- and T-receptors have been consistently explained based on the difference in the relative strengths of the driving and suppressing forces between P- and T-receptor cells. The response properties considered are encoding function, probability of firing of afferent nerve, pattern of damped oscillation, shape of tuning curves, values of the optimum frequency, and response latency.

Afferent Pathways↗
PubMed1996

Mechanism of nonlinear responses of taste cells to mixed tastes.

Coupling between ionic flows through different kinds of channels affects essentially the responses of multisensitive taste cells to single- and mixed-taste stimuli. The mechanism of taste transduction is studied by using a realistic model of the multisensitive cells of the rat. The transduction pathways considered are amiloride-sensitive Na+ channels for NaCl and HCl and adenosine 3',5'-cyclic monophosphate-mediating K+ channels for sucrose. Contributions of paracellular pathways and taste-insensitive ionic channels are also studied. The calculated responses of various multisensitive cells induced by single stimuli of NaCl, HCl, or sucrose reproduce experimentally observed responses as well. The two main conclusions are as follows. 1) Whether the response of a cell to a binary mixture becomes synergetic or antagonistic can be estimated from the individual responses of the cell to each component of the mixture. 2) Whether the response is enhanced or suppressed by addition of a new taste to the original taste can be determined, for most receptive cells, from a viewpoint of linear superposition of the individual responses.

Animals↗
PubMed1995

Development of cockroach-allergic guinea pig by simple room air contamination.

Asthma is frequently associated with inhalant sensitivities, particularly allergens of indoor environment. The aim of the study is to determine whether an indoor allergen, cockroach (CRa), can induce guinea pig sensitization without adjuvant or special manipulation. Six regimens were used in sensitizing guinea pigs by CRa aerosols: low daily (C-I), low intermittent (C-II), high intermittent (C-III), maximum intermittent (C-IV), high daily (C-V) and high alternate day (C-VI) doses, and results were compared with that of intraperitoneal sensitization (C-VII). Also studied was a role of CRa in the aerosol ovalbumin (OA) sensitization in comparison with placebo and an adjuvant, Al(OH)3. Reaginic guinea pig antibodies, anti-CRa-IgGla-like (IgGla) and IgE-like (IgE), were measured by passive cutaneous anaphylaxis (PCA). Results show that IgGla was produced only in high-dose aerosol groups, C-V and C-VI, but no IgE in all aerosol groups. The antibody was detected on day 22 (C-V) and day 19 (C-VI) and sustained till day 52 (titers 1:20 to 1:200). The preliminary pulmonary function measurements revealed that the sensitized animals (C-VI) showed a decreased ventilatory function upon CRa challenge. Aerosolized OA sensitization also produced anti-OA-IgGla in high intermittent regimens. In addition, PCA titers (anti-OA-IgGla) in OA-sensitized animals were not influenced by pretreatment with CRa, Al(OH)3, or placebo. Thus, the study indicates that simple aerosolized CRa contamination in a chamber makes guinea pigs cockroach-sensitive and become asthmatic. Yet, CRa does not enhance other allergen sensitization.

Aerosols↗
PubMed1995

Role of alpha-2-macroglobulin and bacterial elastase in guinea-pig pseudomonal septic shock.

An essential role of alpha-2-macroglobulin (alpha 2M) was revealed in the prevention of septic shock induced in guinea-pigs by an elastase producing strain (IFO-3455) of Pseudomonas aeruginosa. When bacterial peritonitis was induced by inoculating fibrin-thrombin clot containing viable bacteria at a dose of 10(9) c.f.u./kg body weight, the guinea-pigs (n = 6) died within 7-8 hours due to septic shock. Prior to the shock, consumption of two-thirds of the circulating alpha 2M was observed. When circulating alpha 2M was depleted 4 hours after the bacterial inoculation, the guinea-pigs immediately developed shock and died within one hour. This shock was prevented either with a specific elastase inhibitor, HONHCOCH(CH2C6H5)CO-Ala-Gly-NH2, zincov (6 microM), or with human alpha 2M. Simultaneous depletion of circulating Hageman factor also prevented shock in the alpha 2M-depleted animals. These results indicate that septic shock was induced through activation of the Hageman factor dependent system by the bacteria-produced elastase which survived alpha 2M in the circulation.

Animals↗
PubMed1995

Effects of serine protease and deoxyribonuclease on intravascular tumor cell arrest in rat blood-borne lung metastasis.

Effects of alpha-chymotrypsin and deoxyribonuclease I (DNase I) on the early phase of blood-borne lung metastasis in rats were studied using confocal laser scanning microscopy and AH-109A cells labeled either with carboxyfluorescein diacetate succinimyl ester or with 51Cr. Intravenous administration of alpha-chymotrypsin or DNase I appeared to enhance or inhibit, respectively, the tumor cell arrest in lung microvasculature as a reflection of reduction or promotion of the tumor cell clearance in the microvasculature. These results suggest that the effects of alpha-chymotrypsin and DNase I are related to induction of tumor cell aggregation and disaggregation in the blood stream, respectively.

Animals↗
PubMed1995

Rat ultraviolet ray B photodermatitis: an experimental model of psoriasis vulgaris.

Ultraviolet ray B (UV-B) induced dermatitis in the rat may be a model for human psoriasis vulgaris. Detailed studies of this model are reported. Rat skin responded to UV-B irradiation quite differently from human, guinea-pig, or mouse skin. Rat UV-B dermatitis was characterized by a sharply demarcated brownish-red lesion with scale formation lasting for 10 days. Histologically, microvascular dilatation, intraepidermal accumulation of polymorphonuclear leucocytes with microabscess, mononuclear cell infiltration at the papillary dermis and hyperproliferation of epidermal cells were observed. These features were similar to those of clinical psoriasis vulgaris in man. Leucocyte suppression, induced by systemic ferritin administration to the irradiated rats, resulted in loss of the epidermal hyperproliferation and inhibition of the tissue leucocytosis. This leucocyte suppression remodelled the picture of the rat UV-B dermatitis into that seen in other mammalian species, where microvascular dilatation and degeneration of keratinocytes (so-called sunburn cells) are characteristic. The irradiated epidermis of the rats treated with ferritin possessed an in vitro PMN chemotactic property. Rat UV-B dermatitis seems to be a useful model to investigate aetiopathogenic mechanisms in psoriasis vulgaris. However, the former heals after injury and does not relapse as does psoriasis.

Animals↗
PubMed1994

Primary structure of bovine Hageman factor (blood coagulation factor XII): comparison with human and guinea pig molecules.

A bovine Hageman factor cDNA was cloned from a liver cDNA library. The nucleotide sequence was analyzed and the amino-acid sequence was deduced. The sequence deduced was consistent with the partial amino-acid sequences of bovine Hageman factor protein. The sequences for three portions including the amino terminal had been previously reported (Fujikawa et al. (1977) Biochemistry 16, 2270-2278). In comparison with the primary structures of human and guinea pig Hageman factors, the putative domain structures were totally conserved. Each domain possessed high sequence homology with the human molecule (66-88%) and the guinea pig one (63-81%) except for the proline-rich region (less than 10%) which connects the amino-terminal five domains with a serine proteinase portion. Significant heterogeneities were observed among the three species around the essential cleavage sites for the conversion to the activated Hageman factors. Bovine Hageman factor has no suitable amino-acid sequence as the substrate for the trypsin-type proteinases at the proline-rich region in difference from the human and guinea pig molecules. Probably this is the reason why the beta-form activated Hageman factor (the proteinase moiety) is not liberated in the activation of the bovine molecule with trypsin or plasma kallikrein.

Amino Acid Sequence↗
PubMed1994

Alpha-2-macroglobulin as the major defence in acute pseudomonal septic shock in the guinea-pig model.

An intravenous injection of 1.2 mg/kg of Pseudomonas aeruginosa elastase induces immediate lethal shock in guinea-pigs. In the present study, alpha-2-macroglobulin (alpha 2M) was shown to be the major factor in guinea-pig plasma that inhibits the enzymatic activity of elastase in vitro. Depletion of circulating alpha 2M by injecting anti-guinea-pig alpha 2M rabbit IgG F(ab')2 rendered the animals sensitive to a dose of elastase of 0.05 mg/kg. When the alpha 2M-depleted guinea-pigs were reconstituted with human alpha 2M, this sensitivity was reversed. Lethal shock did not occur in alpha 2M-depleted animals even at an elastase dose of 0.2 mg/kg when Hageman factor was simultaneously depleted, indicating that elastase induces shock through activation of the Hageman factor-dependent system. Similar results were obtained when the culture supernatants of an elastase-producing strain, IFO-3455, were used instead of the purified elastase, whereas no cardiovascular changes occurred, even in the alpha 2M-depleted guinea-pigs, when the culture supernatants were pretreated with an elastase specific inhibitor (zincov) or when the culture supernatants of an elastase non-producing strain, PA-103 were used.

Acute Disease↗
PubMed1994

Suppression of polymorphonuclear leucocyte chemotaxis by Pseudomonas aeruginosa elastase in vitro: a study of the mechanisms and the correlation with ring abscess in pseudomonal keratitis.

Bacteria, or the culture supernatants of an elastase non-producing strain of Pseudomonas aeruginosa, elicited a chemotactic response from polymorphonuclear leucocytes (PMN) in vitro. The chemoattractive capacity was diminished under the presence of Boc-Phe-Leu-Phe-Leu-Phe, a receptor antagonist of N-formyl-Met-Leu-Phe (fMLP) which is a bacterial chemotactic peptide to PMN. This indicated that the chemoattractant derived from Pseudomonas aeruginosa was a fMLP-like molecule(s). In contrast, culture supernatants of an elastase producing strain of Pseudomonas aeruginosa produced negligible chemotactic response from PMN. Indeed, an inhibitory effect of the culture supernatants or of purified Pseudomonas aeruginosa elastase (PAE) on PMN chemotaxis was observed when fMLP was used as a chemoattractant. Another fMLP-induced function of PMN, respiratory burst activation, was also diminished by pretreatment of PMN with PAE. PAE hydrolysed fMLP at the Met-Leu bond and diminished the chemoattractant capacity. In addition, a receptor analysis with fML-3H-P demonstrated a decrease in numbers of fMLP receptors on PMN without changing the dissociation constant values after the treatment of the cells with PAE. In the primary structure of the fMLP receptor previously reported, a preferential amino acid sequence for cleavage by PAE was identified in what was believed to be an extracellular portion of the receptor molecule. These results suggested that PAE could diminish PMN infiltration in response to Pseudomonas aeruginosa in vivo by cleavage of the fMLP-like pseudomonal chemotactic ligand and the receptors on PMN.

Abscess↗
PubMed1993

Pseudomonal elastase injection causes low vascular resistant shock in guinea pigs.

An intravenous injection of culture supernatants obtained from an elastase producing strain (IFO-3455) of Pseudomonas aeruginosa exhibited immediate fall of mean arterial blood pressure from 63.8 +/- 1.62 to 35.6 +/- 2.31 mmHg (P < 0.001), increased heart rate from 249.6 +/- 3.86 to 272.6 +/- 2.18 beats/min (P < 0.05), and increased respiratory rate from 44.8 +/- 2.33 to 68.6 +/- 1.60/min (P < 0.01) within 5 min in the anesthetized guinea pigs. In contrast, culture supernatants obtained from an elastase non-producing strain (PA-103) did not cause the cardio-respiratory alterations, even though the same dose of endotoxin was contained in the supernatants. Intravenous or intracardiac injection of purified Pseudomonas aeruginosa elastase (1.2 mg/kg) but not endotoxin (up to 2.0 mg/kg) reproduced the immediate shock followed by death within 45 min in anesthetized or in conscious guinea pigs. Consistently, the shock-inducing ability of pseudomonal elastase was prevented by pretreatment with anti-pseudomonal elastase rabbit F(ab')2 antibodies or with a synthetic inhibitor of pseudomonal elastase. Furthermore, intravenous injection of a non-lethal dose of pseudomonal elastase (0.8 mg/kg) immediately decreased peripheral vascular resistance when estimated from a change of perfusion pressure at hindquarter circulation from 74.0 +/- 1.00 to 52.6 +/- 1.76 mmHg (P < 0.05) in association with fall of arterial blood pressure and of cardiac output which was estimated from a change of regional aortic flow. The same low-resistant shock was also observed in rats. We speculate, therefore, that bacterial proteinases may play an important role in human septic shock.

Animals↗
PubMed1993

Role of Hageman factor/kallikrein-kinin system in pseudomonal elastase-induced shock model.

The role of the Hageman factor dependent pathway in pseudomonal elastase-induced shock was investigated in guinea pigs. Presence of a bradykinin B2 receptor antagonist [D-Arg0,Hyp3,Thi5,8,D-Phe7]-bradykinin (200 nM) in the circulation prevented shock caused by an intrajugular injection of pseudomonal elastase (0.8 mg/kg body weight). During the lethal shock caused by elastase (1.2 mg/kg), a significant consumption of components of the Hageman factor/kallikrein-kinin system was observed such as 45.7 +/- 2.20% consumption of Hageman factor, 100 +/- 0% of prekallikrein, and 85.1 +/- 2.50 of high-molecular-weight kininogen. More striking evidence for the participation of this system was demonstrated in depletion experiments with monospecific F(ab')2 antibodies against the components of the system. After depletion of any one of the components, guinea pigs exhibited unresponsiveness to the same lethal dose of pseudomonal elastase in regard to the cardio-respiratory alterations. In vitro, pseudomonal elastase (60 micrograms/ml) possessed a capacity to generate substantial amount of bradykinin in undiluted plasmas of humans (300.0 +/- 32.16 ng/ml) as well as guinea pigs (460.2 +/- 20.67 ng/ml) at 37 degrees C but not in those deficient in Hageman factor or prekallikrein. These results strongly suggested a pathological role of elastase in pseudomonal sepsis through activation of the Hageman factor dependent pathway.

Amino Acid Sequence↗
PubMed1993

Difference between human and guinea pig Hageman factors in activation by bacterial proteinases: cleavage site shift due to local amino acid substitutions may determine the activation efficiency of serine proteinase zymogens.

Human and guinea pig Hageman factors have been subjected to the action of pseudomonal elastase and serratial E15 proteinase. The pseudomonal elastase cleaved 22-24% of the human molecule at Arg353-Val354, and the remainder at Gly357-Leu358 resulting in the generation of about 20% of potential activity as activated Hageman factor, compared with trypsin activation, while it hydrolyzed Arg340-Ile341 bond in guinea pig molecule and generated about 75% of activity as activated Hageman factor. The serratial proteinase did not hydrolyze the essential cleavage site (Arg353-Val354) of the human zymogen but Gly356-Gly357 (30%) and Gly357-Leu358 (70%) bonds. Both products showed no activity. The guinea pig zymogen, in contrast, was cleaved mostly at Arg340-Ile341 (70%) and less abundantly at Gly344-Leu345 (30%), generating about 85% of the whole potential activity as activated Hageman factor. From the high correspondence between the proportions of activation and of hydrolysis at the essential cleavage site in activation, it was concluded that hydrolysis of the bonds different from the essential bond did not cause activation, even when the spatial separation was only 3 or 4 residues. Considering the amino acid differences between human and guinea pig Hageman factors, -Met351-Thr-Arg-Val-Val-Gly-Gly-Leu-Val-Ala360- and -Leu338-Ser-Arg-Ile-Val-Gly-Gly-Leu-Val-Ala347-, respectively, it was realized that even the minor amino acid substitutions caused the cleavage site shift which resulted in significant differences in activation efficiency of the proteinase zymogens.

Amino Acid Sequence↗
PubMed1993

Role of macrophage tissue factor in the development of the delayed hypersensitivity reaction in monkey skin.

Delayed-type hypersensitivity (DTH) reaction is a cell-mediated immune response, characterized by fibrin deposition. To determine whether macrophage tissue factor (TF), an initiator of blood coagulation, was associated with the DTH reaction, TF expression on macrophages and resulting fibrin deposition at the site of DTH, induced in Bacille-Calmette-Guerin (BCG)-sensitized Japanese monkeys with intradermal administration of pure protein derivative of tuberculin (PPD), were examined immunohistochemically using monoclonal antibodies (MoAbs) against TF and fibrin. Most mononuclear cells, but not polymorphonuclear cells, in DTH reaction sites were TF-positive and were identified as macrophages by double-immunostaining using anti-TF and anti-macrophage MoAbs. Fibrin deposition was only observed around TF-positive macrophages in the stroma of DTH reaction sites, and the deposition was not seen in the periphery of other TF-positive tissues (epidermis, trichoepithelium, and blood vessels). The development of induration and the extent of fibrin deposition paralleled an increase of TF-positive macrophages in the DTH reaction sites. In PPD-injected skin sites of nonsensitized monkeys, neither TF-positive macrophages nor fibrin were seen but epidermis, trichoepithelium, and blood vessels were TF-positive. Moreover, the development of induration was inhibited by simultaneous administration of anti-TF MoAb and PPD into BCG-sensitized monkeys. These results suggest that TF expression on macrophages in the reaction site is a key factor for the DTH reaction, through the activation of blood coagulation, resulting in fibrin deposition.

Animals↗