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T Hayama

Publications and source records attributed to T Hayama.

At least 91 records · Page 5Linked to original sources

Use of the Goettingen miniature pig for studying pyrimethamine teratogenesis.

Although pigs are suitable animals for experimental teratology, use of miniature pigs developed as a medicobiological experimental animal is essential for this purpose. Miniature pigs are established genetically so that the background data on the naturally occurring birth defects are reliable, whereas the commercial breeds are always improved genetically to seek higher productivity. In this review the authors summarized pyrimethamine teratogenesis in Goettingen miniature pigs. Pyrimethamine administration to a pregnant sow during the early stage of the organogenetic period caused cleft palate and other birth defects, and also hind leg paralysis, a functional defect in newborns.

Abnormalities, Drug-Induced↗

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.

Animals↗

Responsiveness of solitario-parabrachial relay neurons to taste and mechanical stimulation applied to the oral cavity in rats.

A total of 311 units, responsive to natural stimulation of the oral cavity, were isolated from the rostral part of the solitary tract nucleus (NTS) of rats. Of these, 169 "taste neurons", activated by taste stimulation, and 142 mechanoreceptive units, exclusively sensitive to mechanical stimulation of the oral cavity, were found. Most taste units (62.3%) were also excited by mechanical stimulation. Forty-three (34.1%) of the 126 taste units examined were identified as solitario -parabrachial relay (SP) neurons by antidromic stimulation from the ipsilateral dorsal pons, while only eleven (12.6%) of the 87 mechano-receptive units were SP neurons. Taste SP neurons could be divided into two subgroups according to their antidromic latency; the fast SP units with an antidromic latency shorter than 9 ms and slow SP units with a longer antidromic latency. These two subgroups were not differentiated in any physiological properties except that the fast SP neurons were frequently excited by sucrose. Taste neurons were classified according to the best stimulus of the four basic taste solutions to produce the largest number of discharges in each neuron. All types of taste neurons were found among the SP and non-SP neurons, but only a small number of quinine-best neurons (n = 2) were found in the SP neuron group compared to the number of quinine-best neurons in the non-SP neuron group (n = 10). A histological examination of the recording sites revealed that taste relay neurons were found at the central or dorsal part of the nucleus but mechanoreceptive relay neurons were found at the peripheral part, although relay and non-relay neurons of either class were intermingled in the nucleus.

Animals↗

Receptive fields of solitario-parabrachial relay neurons responsive to natural stimulation of the oral cavity in rats.

The receptive field (RF) of 67 taste and 85 mechanoreceptive neurons in the solitary tract nucleus (NTS) were located in the oral cavity in albino rats. All of the taste and most (62.4%) of the mechanoreceptive neurons examined had an RF on the ipsilateral side of the tongue and/or the palate. Regardless of whether they were solitario-parabrachial relay (SP) neurons or non-SP neurons, RFs of taste neurons were found on the anterior as well as the posterior tongue. But there were some differences in the RF distribution between the SP and non-SP mechanoreceptive neurons. Most of the mechanoreceptive SP neurons (9 of 11) had an RF on the tongue, while ca. half of the mechanoreceptive non-SP neurons (43 of 79) had an RF on the tongue and palate, but the rest had an RF on other tissue. Most of the neurons studied had a small restricted RF, but complex RFs, e.g. two separate RFs on the tongue, were found in a relatively small number of neurons (four taste and five mechanoreceptive neurons). An inhibitory RF, usually in a remote place from the excitatory RFs, was found in four mechanoreceptive neurons but no inhibitory RFs for taste neurons. Electrical stimulation of the epithelium in the RF with a low current of short duration evoked a few spikes in most units. Two of the three units, giving rise to a vigorous response to taste stimulation, but having single restricted RFs on the anterior tongue, produced a train of spikes lasting more than 20 ms in response to electrical stimulation of the RF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Location and taste responses of parabrachio-thalamic relay neurons in rats.

Thirty of the 55 taste units in the parabrachial nucleus were activated antidromically by stimulation of either or both of the ipsi- or contralateral thalamic taste areas. Such parabrachio-thalamic taste relay neurons produced bilateral thalamic afferent fibers (B type, N = 14), exclusively ipsilateral thalamic afferent fibers (I type, N = 12), or exclusively contralateral thalamic afferent fibers (C type, N = 4). Most of the B-type neurons were excited best by NaCl among the four basic taste stimuli; approximately one-half the I-type neurons by HCl. Most of the NaCl-best neurons were located in the medial part of the parabrachial nucleus but most of the HCl-best neurons were in the lateral part. In addition, NaCl-best neurons had shorter ipsilateral latencies (modal value = 1.0 to 3.0 ms) from the ipsilateral thalamic taste area, whereas HCl-best neurons had longer latencies (modal value = 4.0 to 6.0 ms).

Animals↗

Pharmacokinetic analysis of plasma concentration and urinary excretion of sulphamonomethoxine and its metabolite in Goettingen minipigs.

The plasma concentration and renal excretion after a bolus intravenous injection of a low (10 mg/kg) or high (100 mg/kg) dose of sulphamonomethoxine (SMM) were studied in five Goettingen minipigs. The time data of plasma concentration after a low dose decreased rapidly and appeared to be linear on semilog graph paper. On the other hand, a decrease in the plasma concentration after a high dose was slow at first, gradually accelerated, then became rapid, showing that SMM disposition after a high dose (100 mg/kg) seemed to be non-linear with capacity-limited elimination. A large amount of the acetyl derivative of SMM (AcSMM), which was determined to be the main excretory product of SMM in urine, was detected in the plasma after SMM injection. As the ratios of the area under plasma concentration-time curve of AcSMM to that of SMM were not significantly different at either dose, the acetylation of SMM may be unsaturable by injection of 100 mg/kg of SMM. Immediately after the injection of a low dose, a rapid hyperbolic increase of the fraction of the cumulative amount of the excretory products in urine was observed. On the other hand, the fraction curve at the high dose rose slowly at first, then rapidly and hyperbolically. These results suggested that the non-linear drug disposition after a high dose (100 mg/kg) of SMM in pigs may be the result of a limited capacity for renal excretion of SMM and excretory products, especially the acetyl derivative.

Animals↗

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.

Animals↗

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.

Animals↗

Ia-restricted interaction between normal lymphoid cells and SJL lymphoma (RCS) leading to lymphokine production. I. Enhancement and suppression of antibody formation to TI antigens by supernatants and cells from cocultures of RCS and lymphoid cells.

Addition of gamma-irradiated reticulum cell sarcoma (RCS) cells causes suppression of the antibody response to trinitrophenyl (TNP)-keyhole limpet hemocyanin (KLH)-primed syngeneic SJL spleen cells to TNP-polyacrylamide (PAA) in vitro. The response of anti-brain antigen (BAT) + C-treated spleen cells is not suppressed by gamma-RCS, but is suppressed by cells from 48-hr SJL lymph node or thymus + gamma-RCS cultures. Addition of as few as 2.5 x 10(5) cultured (anti-I-A + C treated to remove gamma-RCS) cells causes significant inhibition of the responses of both syngeneic and allogeneic spleen cells. Treatment of gamma-RCS-induced suppressor cells with anti-BAT + C reduces their suppressive activity. In contrast to the cells, supernatants (SN) from (lymph node (LN) + gamma-RCS) cultures greatly enhance, in an antigen-dependent fashion, the responses of untreated or anti-BAT + C-treated Sephadex G10-passed spleen cells to TNP-PAA. TNP-SIII polysaccharide, or TNP-Ficoll, but not as much to TNP-KLH. Addition of SN as late as Day 3 of culture still causes about half as much enhancement as leaving SN in throughout the culture period, but it has no effect if left with the spleen cells for only the first day of culture. SN contains high levels of IL-2 and IFN-gamma; absorption with cells from an IL-2-dependent cytotoxic T-cell line removes the enhancing activity, while treatment with pH 2 to remove the IFN-gamma has no effect. SN from an IL-2-producing T-cell line (LBRM-33) has a similar effect on antibody production to TI antigens as does SN of (LN + gamma-RCS). The results suggest a marked dependency of PFC responses to TI antigen on IL-2 in all strains examined, including SJL, LAF1, DBA/2Ha, and CBA/N, probably through a direct activation of B cells. The findings also suggest that suppressor T cells, induced by gamma-RCS in syngeneic lymphoid cells, absorb the IL-2 needed for responses to TI antigens in vitro.

Animals↗

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.

Animals↗

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.

Animals↗