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Biomedical subjects

T Tono

Publications and source records attributed to T Tono.

At least 19 recordsLinked to original sources
PubMed1992

c-kit Gene was not transcribed in cultured mast cells of mast cell-deficient Wsh/Wsh mice that have a normal number of erythrocytes and a normal c-kit coding region.

The Wsh is a mutant allele at the W (c-kit) locus of mice. Mice of Wsh/Wsh genotype have white hairs and black eyes. Although adult C57BL/6-Wsh/Wsh mice were not anemic, they showed a remarkable depletion of mast cells. Most homozygous or double heterozygous mutant mice at the W (c-kit) locus, of which mast-cell depletion was comparable to that of Wsh/Wsh mice, are deficient in germ cells. However, male and female Wsh/Wsh mice have an appreciable number of germ cells in their gonads. We investigated the mechanism of specific depletion of mast cells in Wsh/Wsh mice. Cultured mast cells (CMC) derived from the spleen of Wsh/Wsh mice neither attached to normal (+/+) fibroblasts nor survived in the coculture with +/+ fibroblasts. The c-kit messenger RNA (mRNA) was strongly expressed in +/+ CMC, but not detectable in Wsh/Wsh CMC. Despite the lack of c-kit mRNA in Wsh/Wsh CMC, the c-kit mRNA was normally detectable in the cerebellum and weakly detectable in the testis and spleen of Wsh/Wsh mice. No significant changes were found in the nucleotide sequence of the c-kit transcripts obtained from the cerebellum of Wsh/Wsh mice. Development of mast cells, erythrocytes, and germ cells in Wsh/Wsh mice appeared to be parallel with the magnitude of the c-kit gene expression in each cell type.

Anemia↗
PubMed1992

Venous drainage through the internal auditory meatus of the guinea pig cochlea.

The angioarchitecture of the guinea pig cochlea has been investigated closely using light microscopy and resin injections. However, detailed information concerning the vasculature of the modiolus is still unavailable, and even the existence of venous drainage through the internal auditory meatus is not agreed upon. In the present investigation, vascular casts of guinea pig temporal bones were studied using scanning electron microscopy. A vessel, formed by the confluence of the vascular network on the modiolar wall and having a spiral course into the internal auditory meatus was found in the modiolus of the basal turn. The vessel had a venous pattern on its cast surface and, after existing from the internal auditory meatus, drained finally into the dural sinus. These scanning electron microscopic findings were confirmable by serial sections of the dural veins in the internal auditory meatus and the modiolus. The vessel found may correspond to the so-called internal auditory vein, but it would be more appropriate to call it "the vein of the internal auditory meatus," since it appears to be an independent route of venous drainage from the modiolus.

Animals↗
PubMed1992

A case of splenic vein occlusion caused by the intravenous tumor thrombus of nonfunctioning islet cell carcinoma.

We report herein a case of successfully treated advanced, nonfunctioning islet cell carcinoma associated with left-sided portal hypertension. The splenic vein was obstructed by a huge intravenous tumor thrombus developing from the main pancreatic tumor. Direct invasion to adjacent organs such as the spleen, colon, left kidney and stomach was also observed, although liver metastasis was not present. Radical resection was carried out with removal of these five involved organs and the patient is alive without recurrence more than 5 years after surgery.

Adenoma, Islet Cell↗
PubMed1992

Low-frequency modulation of compound action potential in experimental perilymphatic fistula and endolymphatic hydrops.

We have tested the hypothesis that the cause of cochlear dysfunction associated with perilymphatic fistula (PLF) is closely related to endolymphatic hydrops (ELH). Using guinea pigs, we studied the tone-burst elicited compound action potential (CAP) and its modulation as caused by a 50 Hz biasing tone in experimental PLF. We compared these results with those of experimental ELH. Following perilymph aspiration through the perforated round window membrane, mild but significant elevations of CAP thresholds at tested frequencies were found. A reduction in the amplitude of cochlear microphonics (CM) for a 50 Hz sine wave appeared to correlate with these CAP threshold changes. However, there were no significant changes in the modulation effect of the 50 Hz biasing tone on the CAP elicited by an 8 kHz tone burst. This finding differed from that in ears with experimental ELH, in which significant reductions of both 50 Hz CM and the degree of CAP modulation were consistently observed. We concluded that it is unlikely that the underlying mechanisms of a modification to the low frequency response of the base of the cochlea following perilymph aspiration is linked to that of experimental ELH.

Acoustic Stimulation↗
PubMed1992

Biliary interleukin 6 levels as indicators of hepatic allograft rejection in rats.

Interleukin 6 has recently been noted to be present during the rejection response to grafted organs. In this study, we investigated biliary and serum interleukin 6 levels following liver transplantation in rats. IL-6 levels in bile and serum of naive rats were below 0.6 U/ml and 0.5 +/- 0.2 U/ml (mean +/- SD), respectively. Both biliary and serum IL-6 levels showed high values (greater than 10.0 U/ml and greater than 1.6 U/ml, respectively) on the day after transplantation, which seemed to reflect the inflammatory status caused by the surgical stress. Later samplings showed that the kinetics of serum IL-6 differed among the animals without any definite feature related to graft rejection. In contrast, biliary IL-6 levels correlated well with the severity of the rejection response as determined histologically. Biliary IL-6 levels started to rise at the onset of the rejection response (6.6 +/- 0.6 U/ml), increased further with its progression (19.3 +/- 7.8 U/ml), and then finally fell in the terminal stage (less than 2.0 U/ml). Elevation of biliary IL-6 was observed at an early stage when abnormalities could be detected histologically but not in liver function tests and bile flow. Therefore, biliary IL-6 levels may be of value for the early diagnosis of rejection following liver transplantation.

Animals↗
PubMed1992

Permanent acceptance of liver allografts by intraportal injection of donor spleen cells in rats.

Antigen pretreatment through the oral or intraportal route has been reported to suppress antibody formation or delayed-type hypersensitivity (DTH) response to the same antigens. However, this effect on allografted organs has not been well studied. In this study we evaluated the efficacy for suppression of antibody formation and DTH response to the allogeneic antigens and tried to prolong liver allograft survival in rats. Male ACI (RT1a) rats were used as donors and male BUF (RT1b) rats as recipients. Intraportal or intravenous injection of spleen cells (SPCs) (5 x 10(7)) was performed through the mesenteric vein or the tail vein, respectively. The anti-ACI DTH response was tested by ear challenge of ACI SPCs. Cytotoxic antibody was assessed by complement-dependent cytotoxicity assay. ACI rat liver was transplanted orthotopically to BUF rat by the cuff technique 10 days after SPC injection. Cytotoxic antibody titer rose to X2(6) to X2(8) at 7 to 10 days after intravenous injection of SPCs. However, intraportal injection of the cells rarely caused a rise in antibody titer and even strongly suppressed subsequent antibody formation induced by intravenous injection when given 10 days before. The DTH response was also suppressed by intraportal injection of SPCs, with a mean value of 0.18 +/- 0.13 mm versus 0.67 +/- 0.19 mm for controls or 0.46 +/- 0.04 mm with intravenous injection. Liver-allografted rats died between 9 and 11 days, averaging 10.1 +/- 0.7 days in the control group. All seven transplants injected intraportally with donor SPCs survived more than 100 days, whereas six of eight rats injected intravenously with donor SPCs died of bleeding from the surface of the liver grafts within 12 hours after grafting, with signs similar to those of hyperacute rejection. Four of five rats injected intraportally with F344 (third-party) SPCs died of acute rejection in the same way the control rats died. The liver allograft-bearing rats had permanently accepted ACI skin grafts when tested 60 days after liver transplantation but rejected F344 skin grafts in the normal fashion. Intraportal injection of donor SPCs markedly suppressed the antibody formation, as well as the DTH response, and completely blocked liver allograft rejection. Moreover, the liver allograft-bearing rats proved to be fully tolerant of the donor antigen. This method might be a promising modality for inducing donor-specific tolerance in liver transplantation.

Animals↗
PubMed1992

Repeated measurements of compound action potential: evaluation of the ototoxicity of otic drops.

Consecutive CAP threshold shifts were studied in chinchillas following round window application of Cortisporin Otic Suspension for 10 minutes. A marked deterioration in CAP threshold was observed at 24 hours following otic application but these threshold shifts were reversible at lower frequencies. The shifts were progressive at higher frequencies at the 4 week measurement. The progressive high frequency loss with recruitment and with normal EP levels implies some hair cell dysfunction due directly to Cortisporin Otic Suspension ototoxicity and/or secondarily to middle ear inflammatory reactions to the otic. Short-term studies of ototopical drugs may result in misleading assessments as to the pattern and degree of ototoxicity. Long-term (i.e., one month or longer) studies are recommended for accurate ototoxicity assessment.

Action Potentials↗
PubMed1991

Characterization of Ws mutant allele of rats: a 12-base deletion in tyrosine kinase domain of c-kit gene.

Homozygous mutant rats at the newly found white spotting (Ws) locus were anemic and deficient in mast cells and melanocytes. Because the phenotype of Ws/Ws rats resembled the phenotype of mice possessing a double-gene dose of mutant alleles at the W locus and because the c-kit gene was mapped at the W locus of mice, we characterized the c-kit gene of Ws/Ws rats. The authentic sequence of the rat c-kit cDNA was determined by using a cDNA library prepared from the hippocampus of Sprague-Dawley rats. The c-kit cDNA of Ws/Ws and normal (+/+) control rats was obtained by reverse transcriptase modification of the polymerase chain reaction. When compared with the authentic sequence, a deletion of 12 bases was found in the c-kit cDNA of Ws/Ws rats. This change was shown to be a result of the deletion of the genomic DNA. Four amino acids encoded by the deleted 12 bases (ie, Val-Lys-Gly-Asn) were located at two amino acids downstream from the tyrosine autophosphorylation site in the c-kit kinase and were conserved not only in mouse and human c-kit kinases but also in mouse and human c-fms kinases (ie, receptors of colony-stimulating factor-1). Taken together, the Ws/Ws rat is the first characterized mutant of the c-kit gene in an animal species other than the mouse.

Alleles↗
PubMed1991

Suppressor cells induced by donor-specific transfusion and deoxyspergualin in rat cardiac xenografts.

The effect of donor-specific blood transfusion (DST), in combination with pretransplant immunosuppression with deoxyspergualin (DSG), on hamster-to-Wistar rat cardiac xenograft survival was assessed. While DST given on day -6 sensitized the recipients, resulting in hyperacute xenograft rejection, the addition of 5 mg/kg/k/day DSG from the day of transfusion to the day of grafting not only prevented hyperacute rejection but resulted in prolongation of graft survival from 3.4 +/- 0.5 days in untreated controls to 7.0 +/- 0.7 days (P less than 0.01). In contrast, DSG alone as pretransplant immunosuppression had no beneficial effect and rejection occurred in 4.0 +/- 0.7 days. This effect appears to be at least donor species-specific, in the sense that ACI cardiac allograft survival was not prolonged when transplanted into xenotransfused and DSG-treated Wistar recipients. DST alone resulted in marked increase in antibody titers, showing the value of 1:512 or more on transplantation day. On the other hand, combined treatment suppressed the titers to 1:1-1:4 on that day. An adoptive cell transfer system was used to analyze the mechanisms underlying this effect. When sublethally irradiated secondary hosts were transferred with 5 x 10(7) lymph node cells (LNCs) harvested on day 0 from xenotransfused and DSG-treated rats, the test heart xenograft survived longer than the irradiated and nontransferred controls, suggesting the presence of suppressor cells. Further in vitro studies demonstrate that LNCs from DST+DSG-treated rats response less in a mixed lymphocyte reaction to hamster LNCs (41% on day 0 [P less than 0.01]), compared with the controls. In coculture experiments, the LNCs from treated recipients suppressed the response of unmodified Wistar LNCs to hamster LNCs by 76% on day 0 compared with the positive controls (P less than 0.01). On the other hand, the transfer of serum taken from treated rats on day 0 did not lead to prolongation of test heart xenografts in syngeneic naive hosts. These findings suggest that the mechanisms underlying the hyporesponsiveness induced by pretreatment with DST and DSG include the induction of suppressor cells, although a degree of clonal deletion can not be ruled out. The generation of serum suppressor factors seems to have no role in this phenomenon.

Animals↗
PubMed1991

Middle ear inflammatory mediators and cochlear function.

Sensorineural hearing loss (SNHL) has been documented in patients with otitis media. Despite a number of clinical and pathologic works dealing with this common problem, animal studies searching for possible relationships between the middle ear inflammation and cochlear function remain insufficient. Bacterial inoculation and ototoxins and inflammatory products in the middle ear cavity cause SNHL in rodents. Human serum albumin placed in the middle ear cavity in chinchillas also produces SNHL, owing to the effects of nonspecific inflammation in the middle ear cavity. Most of the middle ear inflammatory mediators enter the inner ear through the round window route, and alteration of the permeability of the round window membrane plays an important role in causing cochlear dysfunction. Although an immunologic response in the middle ear plays an important role in otitis media, the immunologic response in the inner ear as it relates to middle ear inflammatory mediators requires further study.

Animals↗
PubMed1990

Evidence that deoxyspergualin prevents sensitization and first-set cardiac xenograft rejection in rats by suppression of antibody formation.

This study provides evidence of antibodies playing an important role in hamster-to-rat cardiac xenograft rejection and discusses the use of 15-deoxyspergualin (DSG) to suppress this first-set rejection, as well as hyperacute rejection induced by sensitization. The effect of recipient splenectomy (Spx) as an adjuvant to DSG to control first set xenograft rejection was also examined. When hyperimmune serum was taken from control recipients at rejection time and injected i.v. into new recipients of cardiac xenografts, hyperacute graft rejection resulted. Survival depended on the amount of serum injected and ranged from 14.7 +/- 2.5 min with 3 ml of serum to 233.3 +/- 61.1 min with 0.5 ml. Experiments on first-set xenograft rejection revealed that a dose of 2.5 mg/kg/day DSG could prolong xenograft survival from 3.4 +/- 0.5 days in untreated controls to 9.5 +/- 2.6 days (P less than 0.01). A dose of 5 mg/kg/day DSG, though it increased graft survival to 16.4 +/- 5.9 days, proved to be toxic to the recipients. Spx alone prolonged xenograft survival to 5.2 +/- 0.4 days, and, when combined with 2.5 mg/kg/day DSG administration, prolonged graft survival to 22.1 +/- 5.5 days (P less than 0.01 vs. DSG alone). The appearance of cytotoxic antibodies was delayed, and titers decreased from 1:256 in untreated controls to 1:16-1:64 both in the group that underwent Spx only and in the group that received 2.5 mg/kg/day DSG. Combined treatment suppressed antibody response for more than two weeks. Experiments on hyperacute rejection induced by sensitization revealed that 1 ml of hamster whole blood transfused into prospective heart recipients 1 week before grafting resulted in graft loss in 18.2 +/- 6.1 min. Pretransplant transfusion and concomitant daily administration of 5 mg/kg/day DSG until one day after grafting not only prevented hyperacute rejection but prolonged graft survival to 7.0 +/- 0.7 days. This survival was significantly longer than with DSG alone (4.2 +/- 0.8 days, P less than 0.01). We concluded that the marked suppression of antibody formation by DSG plays a major role in preventing first-set xenograft rejection and hyperacute rejection induced by sensitization.

Animals↗