Studies of the effects of FK506 on renal allografting in the beagle dog

Takenori Ochiai, M. Nagata, K. Nakajima, T. Suzuki, K. Sakamoto, K. Enomoto, Y. Gunji, T. Uematsu, Takesada Goto, S. Hori, Takashi Kenmochi, T. Nakagouri, T. Asano, K. Isono, K. Hamaguchi, H. Tsuchida, K. Nakahara, N. Inamura, Toshio Goto

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Abstract

The immunosuppressive activities of a newly discovered macrolide extracted from Streptomyces tsukubaen-sis, FK506, were examined using 38 renal allografts in the beagle dog. The median survival time was 15.5 days in dogs without treatment, 61 days with a dose of 0.08 mg/kg/day and 176 days with a dose of 0.16 mg/kg/day of intramuscularly administered FK506. Prolongation of survival was statistically significant when compared with controls (P = 0.02, 0.0044, respectively). None of 6 recipient dogs receiving the agent at a dose of 0.16 mg/kg/day encountered rejection during the treatment course. Three of them survived over 200 days. Oral administration of FK506 at a dose of 0.32 mg/kg/day did not prolong the median survival time (20.5 days) compared with the placebo treated control (16.5 days), but oral treatment with 1.0 mg/kg/day resulted in all of the recipient dogs surviving over 130 days. Histological studies of 7 kidney graft biopsy specimens of the dogs surviving over 3 months revealed no cell infiltration or only some degree of reversible interstitial cell infiltration, but vascular and glomerular changes were not observed in any of the specimens. Irregularity of nuclear shape and cytoplasmic vacuolation of the pars recta of the proximal tubules were observed in one dog each. Liver biopsy specimens showed no consistent evidence of hepatocellular damage. Three dogs died of intussusception 2–3 weeks posttransplant. The dogs treated intramuscularly with 0.32 mg/kg/day suffered from anorexia. Two dogs receiving oral treatment at a dose of 1.0 mg/kg developed papilloma of the skin around day 60, but the tumors disappeared by day 120. We conclude that FK506 is a powerful immunosuppressant in the dog with tolerable side effects.

Original languageEnglish
Pages (from-to)729-733
Number of pages5
JournalTransplantation
Volume44
Issue number6
DOIs
Publication statusPublished - 01-01-1987

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Homologous Transplantation
Tacrolimus
Dogs
Kidney
Immunosuppressive Agents
Biopsy
Intussusception
Macrolides
Papilloma
Streptomyces
Anorexia
Therapeutics
Rectum
Allografts
Blood Vessels
Oral Administration
Placebos
Transplants
Skin
Liver

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Ochiai, T., Nagata, M., Nakajima, K., Suzuki, T., Sakamoto, K., Enomoto, K., ... Goto, T. (1987). Studies of the effects of FK506 on renal allografting in the beagle dog. Transplantation, 44(6), 729-733. https://doi.org/10.1097/00007890-198712000-00001
Ochiai, Takenori ; Nagata, M. ; Nakajima, K. ; Suzuki, T. ; Sakamoto, K. ; Enomoto, K. ; Gunji, Y. ; Uematsu, T. ; Goto, Takesada ; Hori, S. ; Kenmochi, Takashi ; Nakagouri, T. ; Asano, T. ; Isono, K. ; Hamaguchi, K. ; Tsuchida, H. ; Nakahara, K. ; Inamura, N. ; Goto, Toshio. / Studies of the effects of FK506 on renal allografting in the beagle dog. In: Transplantation. 1987 ; Vol. 44, No. 6. pp. 729-733.
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abstract = "The immunosuppressive activities of a newly discovered macrolide extracted from Streptomyces tsukubaen-sis, FK506, were examined using 38 renal allografts in the beagle dog. The median survival time was 15.5 days in dogs without treatment, 61 days with a dose of 0.08 mg/kg/day and 176 days with a dose of 0.16 mg/kg/day of intramuscularly administered FK506. Prolongation of survival was statistically significant when compared with controls (P = 0.02, 0.0044, respectively). None of 6 recipient dogs receiving the agent at a dose of 0.16 mg/kg/day encountered rejection during the treatment course. Three of them survived over 200 days. Oral administration of FK506 at a dose of 0.32 mg/kg/day did not prolong the median survival time (20.5 days) compared with the placebo treated control (16.5 days), but oral treatment with 1.0 mg/kg/day resulted in all of the recipient dogs surviving over 130 days. Histological studies of 7 kidney graft biopsy specimens of the dogs surviving over 3 months revealed no cell infiltration or only some degree of reversible interstitial cell infiltration, but vascular and glomerular changes were not observed in any of the specimens. Irregularity of nuclear shape and cytoplasmic vacuolation of the pars recta of the proximal tubules were observed in one dog each. Liver biopsy specimens showed no consistent evidence of hepatocellular damage. Three dogs died of intussusception 2–3 weeks posttransplant. The dogs treated intramuscularly with 0.32 mg/kg/day suffered from anorexia. Two dogs receiving oral treatment at a dose of 1.0 mg/kg developed papilloma of the skin around day 60, but the tumors disappeared by day 120. We conclude that FK506 is a powerful immunosuppressant in the dog with tolerable side effects.",
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Ochiai, T, Nagata, M, Nakajima, K, Suzuki, T, Sakamoto, K, Enomoto, K, Gunji, Y, Uematsu, T, Goto, T, Hori, S, Kenmochi, T, Nakagouri, T, Asano, T, Isono, K, Hamaguchi, K, Tsuchida, H, Nakahara, K, Inamura, N & Goto, T 1987, 'Studies of the effects of FK506 on renal allografting in the beagle dog', Transplantation, vol. 44, no. 6, pp. 729-733. https://doi.org/10.1097/00007890-198712000-00001

Studies of the effects of FK506 on renal allografting in the beagle dog. / Ochiai, Takenori; Nagata, M.; Nakajima, K.; Suzuki, T.; Sakamoto, K.; Enomoto, K.; Gunji, Y.; Uematsu, T.; Goto, Takesada; Hori, S.; Kenmochi, Takashi; Nakagouri, T.; Asano, T.; Isono, K.; Hamaguchi, K.; Tsuchida, H.; Nakahara, K.; Inamura, N.; Goto, Toshio.

In: Transplantation, Vol. 44, No. 6, 01.01.1987, p. 729-733.

Research output: Contribution to journalArticle

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AU - Sakamoto, K.

AU - Enomoto, K.

AU - Gunji, Y.

AU - Uematsu, T.

AU - Goto, Takesada

AU - Hori, S.

AU - Kenmochi, Takashi

AU - Nakagouri, T.

AU - Asano, T.

AU - Isono, K.

AU - Hamaguchi, K.

AU - Tsuchida, H.

AU - Nakahara, K.

AU - Inamura, N.

AU - Goto, Toshio

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N2 - The immunosuppressive activities of a newly discovered macrolide extracted from Streptomyces tsukubaen-sis, FK506, were examined using 38 renal allografts in the beagle dog. The median survival time was 15.5 days in dogs without treatment, 61 days with a dose of 0.08 mg/kg/day and 176 days with a dose of 0.16 mg/kg/day of intramuscularly administered FK506. Prolongation of survival was statistically significant when compared with controls (P = 0.02, 0.0044, respectively). None of 6 recipient dogs receiving the agent at a dose of 0.16 mg/kg/day encountered rejection during the treatment course. Three of them survived over 200 days. Oral administration of FK506 at a dose of 0.32 mg/kg/day did not prolong the median survival time (20.5 days) compared with the placebo treated control (16.5 days), but oral treatment with 1.0 mg/kg/day resulted in all of the recipient dogs surviving over 130 days. Histological studies of 7 kidney graft biopsy specimens of the dogs surviving over 3 months revealed no cell infiltration or only some degree of reversible interstitial cell infiltration, but vascular and glomerular changes were not observed in any of the specimens. Irregularity of nuclear shape and cytoplasmic vacuolation of the pars recta of the proximal tubules were observed in one dog each. Liver biopsy specimens showed no consistent evidence of hepatocellular damage. Three dogs died of intussusception 2–3 weeks posttransplant. The dogs treated intramuscularly with 0.32 mg/kg/day suffered from anorexia. Two dogs receiving oral treatment at a dose of 1.0 mg/kg developed papilloma of the skin around day 60, but the tumors disappeared by day 120. We conclude that FK506 is a powerful immunosuppressant in the dog with tolerable side effects.

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Ochiai T, Nagata M, Nakajima K, Suzuki T, Sakamoto K, Enomoto K et al. Studies of the effects of FK506 on renal allografting in the beagle dog. Transplantation. 1987 Jan 1;44(6):729-733. https://doi.org/10.1097/00007890-198712000-00001