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Biomedical subjects

H Takagi

Publications and source records attributed to H Takagi.

At least 1,099 records · Page 61Linked to original sources

Evidence that substance P and somatostatin transmit separate information related to pain in the spinal dorsal horn.

Effects of various types of natural skin stimuli on the in situ release of immunoreactive substance P and somatostatin from the rabbit dorsal horn were examined. Noxious mechanical or thermal stimuli specifically increased the release of immunoreactive substance P or somatostatin, respectively. Innocuous stimuli did not affect the release of these peptides. These results suggest that the nociceptive mechanical or thermal primary afferents contain substance P or somatostatin, respectively.

Animals↗

Purification and identification of endogenous anti-opioid substances from bovine brain.

Two fractions with high potency for reversing the inhibitory effect of Met-enkephalin on the electrically induced contractility of guinea-pig ileum have been purified from bovine brain extract. Unexpectedly, one isolated peptide was identified as [Val5]-angiotensin I and the other fraction was [Val5]-angiotensin II, as judged by chromatographic comparisons on HPLC and amino acid analysis. Since angiotensins did not affect opioid binding to brain membrane, we consider that angiotensins may act as physiological antagonists to the opioid system in the brain, as well as in the guinea-pig ileum.

Amino Acids↗

Total pelvic exenteration for advanced carcinoma of the lower colon.

Thirteen patients with advanced carcinoma of the lower colon and no evidence of extrapelvic metastasis were submitted to total pelvic exenteration. Nine of the 13 patients had ureteral urinary diversion by the ileal segment conduit. Three had colonic conduit bladder using the terminal portion of the descending colon. One patient had bilateral uretero colonic anastomosis. The operative mortality rate was 7.7%. Determinate 5-year survival rate of 38.5% was achieved. Histological examinations of the surgical specimen revealed associated abscesses adjacent to the tumor in six cases, although the cancer extended to the bowel wall and adhered to the surrounding structures in all specimens. Total pelvic exenteration assures a better quality of life, lessening of symptoms, disease control and, in selected patients, a cure.

Adenocarcinoma↗

Diagnosis and operation for locally recurrent rectal cancer.

Local recurrence of rectal cancer following abdominoperineal resection is rarely amenable to limited resection. Six patients with deeply invading recurrent lesions had pelvic exenteration combined with sacral resection. This procedure seems a reasonable treatment for palliation and the chance of cure in selected patients. In order to select good candidates for this extensive procedure, carcinoembryonic antigen (CEA) assays and the diagnosis of locally recurrent tumor with pelvic computed tomography (CT) were evaluated. CEA assay is valuable for diagnosing most recurrent rectal cancers, but it is inadequate for early detection. A high CEA level often indicates extrapelvic tumor spread. CT examination is very valuable for the early detection and localization of recurrence in relation to pelvic structures.

Adenocarcinoma↗

Diagnosis and management of cavernous hemangioma of the liver.

Cavernous hemangiomas are the most common benign tumors of the liver, which are now seen more often thanks to common use of newer imaging techniques. A review of the literature on cavernous hemangiomas of the liver, including our own experience with 14 cases, provides data as a touchstone for discussion of the incidence, etiology, symptoms, pathology, diagnosis including ultrasound, radionuclide imaging, computed tomography and angiography, management including resection, hepatic artery ligation, radiation and corticosteroid, and the natural history of these lesions. The author concludes that surgical resection of cavernous hemangiomas should be undertaken with due concern for the relation between the severity of symptoms and the operative risks involved.

Adrenal Cortex Hormones↗

Dystrophic axons in the nucleus gracilis of the normal rat containing cholecystokinin-like immunoreactivity. Light- and electron-microscopic observations.

Cholecystokinin immunoreactive (CCKI) axons in the nucleus gracilis of the normal rat were studied by light and electron microscopy using the peroxidase-antiperoxidase (PAP) immunocytochemical method. Immunoreactivity was found in both normal and dystrophic axons at various ages. Slightly enlarged CCKI varicosities were first observed in 2-month-old rats, gradually increased in number (max. at 21 months) and in diameter (up to 20 micron at 21 months), and then decreased (at 27 and 36 months). Dilatated CCKI fibers continuous with dystrophic varicosities also tended to increase proportionally in diameter. The dystrophic CCKI axonal profiles, first identified at the light-microscopic level and then observed under electron microscopy, had consistently characteristic features. In addition, numerous dystrophic nonreactive axonal profiles had morphological features differing from those of dystrophic reactive ones at advanced ages. These findings suggest that CCK may be partly involved in the formation of dystrophic axons in the nucleus gracilis.

Aging↗

Cyclosporin A effective therapy for fifty-two cadaver kidney recipients.

Fifty-two consecutive patients receiving cadaveric renal transplants were prescribed cyclosporin A and steroid therapy. Three of the recipients underwent re-transplantation and two of the patients were grafted with kidneys shipped from the United States. One year actuarial patient and graft survival rate with no exclusions were 94.2 percent and 81.6 percent, respectively, this rate being significantly better than results in case of the conventional combination of azathioprine, steroid and antilymphocyte globulin. The role of HLA-DR matching on cyclosporin A treatment was studied. One year actuarial graft survival rates of two HLA-DR matched and one HLA-DR matched were 91.7 percent and 78.9 percent, respectively. To assess the effects of cyclosporin A in the management of patients with acute tubular necrosis, the patients were divided into two groups, in terms of whether or not hemodialysis treatment was required for acute tubular necrosis. Although in the present protocol, cyclosporin A administration was begun before the operation, no significant differences in the graft survivals were evident between the two groups. Nephrotoxicity, hepatotoxicity and other side-effects of cyclosporin A could usually be dealt with by dosage adjustments, making feasible the chronic ingestion of this agent. The exceptional effectiveness and safety of cyclosporin A were evident throughout these early trials.

Adolescent↗

Met-enkephalin and morphine but not dynorphin inhibit noxious stimuli-induced release of substance P from rabbit dorsal horn in situ.

The effects of locally applied opioids on the release of immunoreactive Substance P (iSP), induced by mechanical stimuli, from the dorsal horn of the rabbit in situ, were investigated. Morphine and met-enkephalin (met-enk), but not dynorphin A (1-17) (DYN), in a concentration of 10 microM, significantly inhibited the evoked release. These inhibitory effects of morphine and met-enkephalin were antagonized by the local application of naloxone (10 microM) to the dorsal horn. These results suggest that the inhibition of the release of Substance P induced by noxious mechanical stimuli may be mediated by mu and delta, but not by kappa opioid receptors.

Animals↗

Intracerebroventricular administration of angiotensin II attenuates morphine-induced analgesia in mice.

The central effect of angiotensin II on the analgesic action of morphine in mice was investigated using the tail-pinch and hot plate tests. Angiotensin II (0.1-10 pmol), given intracerebroventricularly (i.c.v.), had no effect on the nociceptive sensitivity but did produce a dose-dependent attenuation of the morphine-induced analgesia. A specific angiotensin II antagonist, Saralasin (1 pmol), which in itself had no analgesic effect, significantly potentiated the morphine-induced analgesia. These results suggest that angiotensin II probably plays the physiological role of an anti-opioid substance in pain-modulating systems in the brain.

Analgesia↗

Sites of analgesic actions of kyotorphin and D-kyotorphin in the central nervous system of rats.

Kyotorphin(KTP) and its analog D-kyotorphin(D-KTP) which is resistant to enzyme degradation produced dose-dependent analgesic effects in the tail-pinch test when applied locally to the periaqueductal gray (PAG), nucleus reticularis paragigantocellularis(NRPG) and lumbosacral subarachnoid space(LSS) near the spinal dorsal horn in rts. ED50 values of both dipeptides at the PAG, NRPG and LSS were: 59.0, 105 and 52.6 micrograms/rat for KTP, and 6.2, 8.8 and 10.6 micrograms/rat for D-KTP, respectively. Pretreatment with naloxone(1 mg/kg s.c.) significantly inhibited the analgesic effects of KTP and D-KTP at the PAG and LSS but not at the NRPG. Simultaneous administration of bestatin (2.5 or 50 micrograms) with KTP enhanced the analgesic effect of KTP in the PAG and LSS but not in the NRPG. These findings suggest that the analgesic actions of KTP and D-KTP result from two different mechanisms, 1)enkephgalin-releasing mechanism in the PAG and spinal dorsal horn, and 2)a mechanism without involvement of enkephalin-releasing actions in the NRPG.

Analgesics↗

How is kyotorphin (Tyr-Arg) generated in the brain?

Kyotorphin (Tyr-Arg) was rapidly degraded in the brain homogenates and purified membrane-bound aminopeptidase from monkey brains. The degradation of kyotorphin by these preparations was effectively inhibited by bestatin. When brain homogenates or slices were incubated with bestatin, kyotorphin was accumulated time-dependently in a rate of 1.0 or 2.1 pmol/mg protein/hr, respectively. The bestatin-induced kyotorphin accumulation was inhibited by leupeptin, p-chloromercuribenzoate, but not phenylmethylsulfonylfluoride or diisopropylphosphate. The kyotorphin accumulation was concentrated in the P2 (crude mitochondrial) fraction, particularly in the particulate or synaptosomal fraction. These findings suggest that kyotorphin may be generated in vitro from precursor proteins by membrane-bound, leupeptin-sensitive "kyotorphin converting enzymes" in close vicinity to membrane-bound aminopeptidase which rapidly degrades kyotorphin generated.

Animals↗

Construction of novel shuttle vectors and a cosmid vector for the glutamic acid-producing bacteria Brevibacterium lactofermentum and Corynebacterium glutamicum.

Novel cloning vectors for glutamic acid-producing bacteria have been constructed. Two cryptic plasmids, pAM330 from Brevibacterium lactofermentum and pHM1519 from Corynebacterium glutamicum, were used as precursors, and recombined with pBR325 or pUB110. Resultant composite plasmids were able to propagate and to express the CmR or KmR phenotype in B. lactofermentum and C. glutamicum. A smaller, high-copy-number plasmid, pAJ43, was also isolated following deletion of a part of the pAM330-pBR325 composite plasmid. Furthermore, a cosmid vector, which can be packaged and transduced through phage infection, has been developed using a cohesive-end fragment of the f1A phage and plasmid pAJ43. These plasmids are suitable for use as cloning vectors in the glutamic acid-producing bacteria.

Brevibacterium↗

The influence of renal sympathetic nerves on renal hemodynamic and renin responses during hypercapnia in dogs.

Studies were conducted in anesthetized dogs to examine the influence of the renal sympathetic nerves on renal hemodynamic and renin responses during controlled hypercapnia. The dogs were subjected to unilateral denervation and tested for their responses to hypercapnia induced by inhalation of 15% CO2 in air. Simultaneous measurements of the responses from both the denervated and innervated kidneys allowed an assessment of the influence of the renal nerves on the responses during acute hypercapnia. The data indicate that reductions in renal blood flow and glomerular filtration rate and increases in renin of the renal vein during respiratory acidosis are dependent, in part, on the presence of intact renal nerves. Other factors, however, are probably also present.

Animals↗

[Effect of pirprofen on bradykinin-induced flexor reflexes of rat and rabbit hindlimbs].

The analgesic effects of pirprofen on bradykinin-induced flexor reflexes in rats and rabbits were investigated in comparison with those of indomethacin and ibuprofen by oral administrations. The bradykinin-induced flexor reflexes in rats were suppressed by pirprofen at 10 mg/kg-200 mg/kg, the effect reaching plateau at over 30 mg/kg. Suppression at the dose of 200 mg/kg was 56%. A similar dose-dependent curve was obtained for ibuprofen at 30 mg/kg-300 300 mg/kg. On the other hand, indomethacin exerted dose-dependent inhibition at 1 mg/kg-10 mg/kg without a tendency to reach the plateau effect within this dose range. Suppression at the dose of 10 mg/kg was 83%. The ED50 values of pirprofen, indomethacin and ibuprofen were 68 mg/kg, 3.3 mg/kg and 94 mg/kg, respectively. On the bradykinin-induced flexor reflexes in rabbits, pirprofen showed 60% suppression at the dose of 10 mg/kg, of which the effects were roughly equivalent to those of indomethacin and ibuprofen at the same dosage. These results indicate that there is a species difference concerning the three drug activities on bradykinin-induced flexor reflexes between the rat and the rabbit.

Animals↗

Histologic features and bile duct lesions in the alcoholic.

Histologic features of 112 liver biopsy specimens from patients with alcoholic liver injury were studied. Alcoholic hyalin was found in 6 specimens (5.4%). Spherical giant mitochondria were detected in 9 specimens (8.0%). Fatty metamorphosis, infiltration by polymorphonuclear leucocytes, and pericellular fibrosis were observed in many specimens. Zonal or submassive necrosis was also found in 20 specimens (17.9%). Cholestasis was seen in 32 specimens (28.6%). Histologic changes in interlobular bile ducts were investigated in 103 specimens containing such ducts. Among 31 specimens with cholestasis, changes in interlobular bile ducts were detected in 19 specimens (61.3%), whereas biopsy specimens without cholestasis showed the changes in only 4 of 72 (5.6%). Changes observed in interlobular bile ducts included inflammatory cell infiltration and vacuolation of epithelium in most specimens. Swollen or flattened epithelial cells, karyopyknosis and eosinophilic degeneration were observed in many. These results suggest that the changes of interlobular bile ducts may be partially related to cholestasis in alcoholic liver injury.

Bile Ducts↗