Pancreaticoduodenal allotransplantation with FK 506 in the dog.
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Animals↗
Biomedical subjects
T Morimoto
Publications and source records attributed to T Morimoto.
[The influence of volume expansion with induced hypertension on vessel reactivities, blood-brain-barrier, cerebral edema and infarction].
Eighteen anesthetized cats were randomly divided into 3 groups. One group was treated with 10 ml/kg of 6% hydroxyethyl starch (HES). Another group was treated with 15 ml/kg, and there was a control group. There were six cats in each group. Cerebral pial arterial reactivities were measured by means of intravital microscopic observation through a cranial window. Middle cerebral artery (MCA) was clipped for 70 minutes using a transorbital approach. Five hours later, Evans blue dye was injected intravenously and then the animals were killed. Administration of HES or Ringer's solution (control) was started 15 minutes before clipping of MCA. Systemic arterial pressure was elevated by using dopamine at the same time as the MCA occlusion was carried out. Pial arteries dilated soon after the clipping of MCA in all three groups, but showed different patterns in each group after recirculation of MCA. In the control group, they returned to 20% of their dilated state first, but, after about 4 hours, they redilated by 45% at the end of experiment periods. In the group treated with 10 ml/kg of 6% HES, they remained in an almost resting state after MCA recirculation, but in the group with 15 ml/kg, they constricted by 10% at the end of the experiment periods. Regarding the Evans blue dye extravasation, cerebral edema and infarction, they were largest in the control group. But animals treated with 15 ml/kg of 6% HES showed significantly larger Evans blue dye extravasation and cerebral edema than that of animals with 10 ml/kg. However cerebral infarctions were almost the same sizes in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[A study of pial vessel behavior on superior sagittal sinus and cortical venous occlusion].
In cerebral circulation, it is suspected that neurogenic or myogenic mechanism protect blood vessel and blood-brain barrier during sudden increase in arterial pressure. To discriminate metabolic mechanism from neurogenic and myogenic mechanism, complete cerebral venous occlusion model of cat was used to obtain high venous pressure. In twenty-one anesthetized cats, 0.3 ml of cyanoacrylate were injected into anterior part of SSS to occlude SSS and cortical vein. Diameter of pial vessels and ICP were measured through the cranial window. An average of ICP was 6.7 +/- 1.8 mmHg before occlusion. 5 minutes after occlusion ICP was elevated to an average of 10.4 +/- 4.8 mmHg. Finally, ICP increased over 20 mmHg in nine animals. All pial vein dilated immediately after injection of cyanoacrylate and the dilatation rate was 2-55%. Pial arteriole between 50 microns and 100 microns in diameter was observed. In early stages, 2-24% contraction of arteriole were observed in fifteen animals and 2-16% dilatation were observed in six animals. In later stages, 1-87% dilatation of arteriole were observed in ten cats. Ten of twelve ( 83%) cases with ICP under 20 mmHg showed contraction of pial arteriole. Eight of nine (89%) cases with ICP over 20 mmHg showed dilatation of pial arteriole. In addition, the elevation of ICP and the dilatation of pial arteriole were observed simultaneously. Correlation between ICP and arterial diameter is obvious. The dominant mechanism of cerebral blood flow control is metabolic, not neurogenic and myogenic. Increase of ICP, dilatation of vein and dilatation of artery with increasing ICP are consistent with the theory.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Chemoendocrine therapy in DMBA-induced rat mammary carcinoma.
In the present study, chemotherapy with 5-fluorouracil(5-Fu), endocrine therapy with tamoxifen (TAM), and chemoendocrine therapy with concominant use of 5-FU and TAM were performed and compared for DMBA-induced rat mammary carcinoma, a hormone-dependent tumor. The study was designed to assess the usefulness of chemoendorine therapy based on the antitumor effects and changes in hormone receptor levels. The response rates in the groups treated with 5-Fu or TAM alone and the combination of 5-Fu and TAM were 60%, 50% and 62%, respectively. There was no difference in these response rates. The tumor regression rates in these treatment groups were 22 +/- 69%, 20 +/- 54% and 46 +/- 37%; again there was no difference among the three groups. After treatment, the estrogen receptor (ER) and progesterone receptor (PgR) levels decreased significantly in the groups treated with TAM alone and the combination of 5-FU and TAM but remained unchanged in the group treated with 5-FU alone. The decreases in the ER and PgR levels in responsive tumors after treatment were considerably greater in the groups greated with TAM alone and the combination of 5-FU and TAM than in the group treated with 5-FU alone. However, the changes in the receptor levels in nonresponsive tumors did not differ among the three treatment groups. Moreover, there were no differences in the antitumor effects and changes in receptor levels between the groups treated with TAM alone and the combination of 5-FU and TAM. These results suggest that the antitumor effect observed in the combination therapy with 5-FU and TAM was mainly due to the action of TAM. In brief, the expected additive effects of chemoendocrine therapy were not observed.
9,10-Dimethyl-1,2-benzanthracene↗
[A case of achondroplasia showing diffuse spinal canal stenosis].
A rare case of achondroplasia showing diffuse spinal canal stenosis is presented. A 39-year-old woman was admitted to our hospital because of numbness of lower extremities and intermittent claudication. The patient's height was 121cm and she had the typical clinical features of an achondroplastic dwarf. Neurological examination revealed spastic paraparesis, and sensory impairment below the level of T11 in the left side and L1 in the right. A plain X-ray feature of the spine showed spinal canal stenosis. The interpedicular distances were short in all vertebrae, and especially more prominent in the caudal lumbar region. The sacrum laid horizontally and the sacral angle was narrower than normal case. Myelography and computed tomographic myelography demonstrated severe stenosis of the subarachnoid space at the level of T9-11. Laminectomy was performed from the inferior half of T9 to T11. The yellow ligaments were prominently hypertrophic and these were removed as far as possible. Postoperatively, the weakness of the lower extremities was improved immediately, but numbness remained. Five months after the operation, she suffered from urinary dysfunction, so further laminectomy from T12 to L5 was performed. Also in this operation, hypertrophic yellow ligament was pathognomonic. Following this operation the patient had a good recovery course and returned to work.
Achondroplasia↗
[The experimental study for autoperfused heart-lung preservation--evaluation of pulmonary function after transplantation].
Although various methods for keeping long term good pulmonary function have so far been studied, no reliable method for heart-lung preservation has been established yet. Recently, we aimed at heart-lung preservation using the autoperfusion method and mainly examined pulmonary function after transplantation. After preserving heart-lung organ blocks extracted from mongrel dogs by autoperfusion method, 10 left lungs (preserved for 6.8 +/- 0.8 h) were orthotopically transplanted and combined heart-lung transplantation was performed under extracorporeal circulation using 5 heart-lung grafts (preserved for 7.5 +/- 0.5 h). All of lung-transplanted dogs were alive; preserved lungs showed good gas exchange power from immediately after transplantation. Left lungs on the 3rd day showed normal histological findings and chest X-P also revealed good pneumatization of transplanted lungs. The heart-lung transplantation enabled 4 cases to be free from extracorporeal circulation and arterial blood gas analysis also revealed good results [PO2 396.5 +/- 34.7 mmHg, PCO2 35.5 +/- 6.9 mmHg (FiO2 1.0)]. Lung tissue findings after 6 hours from the above freedom showed slight edema alone. The above results suggested the effectiveness of the autoperfusion method for heart-lung preservation.
Animals↗
[Discriminate function of diabetes mellitus (DM) for screening test by serum 3 lipids and glucose].
The purpose of this study was to establish a program to differentiate diabetic patients in computerized health check data using serum lipid test data. We selected 4 items (TC, FC, TG and Glu) as a marker of clusters for further study on the strength of data obtained from cluster analysis using chemical data obtained on 134 patients. Next we tried principal analysis of the 4 items and computed parameters of component 1 & component 2, and obtained a function (D) to discriminate DM. Function (D) is read from comp. 1 and comp. 2. Comp. 1 = (0.89 x TC + 0.95 x FC + 0.75 x TG + 0.24 x Glu) Comp. 2 = (-0.26 x TC -0.21 x FC + 0.27 x TG + 0.93 x Glu) D = (0.2 x comp. 1 + comp. 2-160) DM patients show D greater than = 0 and non-DM patients D less than 0. We applied data on 587 patients (including of 43 DM) incorporating function (D) to check the property. The results proved it useful as a screening test for diabetic patients. The parameters of function (D) are influenced by inter-laboratory differences. However, our parameters were still effective. Data obtained from other laboratories incorporating our parameter gave a diagnostic quality of more than 70%.
Blood Glucose↗
Comparisons of interval breast cancers with other breast cancers detected through mass screening and in outpatient clinics in Japan.
In a nation-wide collaborative study on mass screening for breast cancer, we collected 152 cases of interval breast cancer diagnosed at 35 hospitals or clinics distributed throughout Japan. The definition of interval breast cancer used in the present study is "breast cancer cases which were diagnosed as having 'no malignant findings' in a previous screening for breast cancer but subsequently diagnosed as 'breast cancer' at a hospital or medical clinic within two years of the previous screening." The clinical stages and prognoses of these interval cancer were analyzed and compared with those of other breast cancers detected through mass screening and in outpatient clinics. In the clinical staging of interval breast cancer, Tis (non infiltrating cancer) accounted for only 2.1%, compared to 8.0% in cases detected through mass screening. At stage I 43.4% were interval breast cancers compared to 32.9% breast cancers detected through mass screening and 25.4% diagnosed in outpatient clinics. The stage differences between interval breast cancers and breast cancers detected through mass screening were not statistically significant. Five-year survival rates were 85.6% for interval breast cancers, 91.7% for breast cancers detected through mass screening and 84.7% for breast cancers diagnosed in outpatient clinics. Ten-year survival rates were 75.9, 80.5 and 78.1%, respectively, suggesting the interval breast cancer cases to show a similar prognosis to that of breast cancer cases diagnosed in outpatient clinics. The differences in five- and 10-year survival rates among the three groups were not statistically significant. From the present study we were not able to confirm the general belief of interval cancer being more aggressive in nature and showing a poorer prognosis than cancer detected through periodic screening. The reasons for this are discussed.
Adult↗
[Sex hormone-binding globulin in breast cancer].
Serum level of sex hormone-binding globulin (SHBG) was measured by immunoradiometric assay in fifty two breast cancer patients and twenty nine healthy female volunteers. The results are as follows: 1) Although the serum SHBG concentration showed no significant difference between the breast cancer group and the healthy control group, the serum SHBG concentration in postmenopause was significantly higher in the breast cancer group (63.8 +/- 31.2nmol/ml/ml; mean +/- S.D.) than in the healthy control group (40.1 +/- 15.4nmol/ml). 2) Subsequently in the postmenopausal breast cancer group, the serum SHBG concentration was significantly higher in the estrogen receptor (ER)-negative cancer group (97.8 +/- 12.7nmol/ml) than in the ER-positive cancer group (55.8 +/- 32.1nol/ml). 3) No significant relationships were showed between the serum SHBG concentration and obesity or serum estradiol concentration in postmenopausal patients. 4) The serum SHBG concentration showed significant decrease 3 months after radical operation for breast cancer in postmenopausal patients. These results suggest the possibility of the SHBG synthesis in breast cancer tissue.
Adult↗
Modifications of masticatory behavior after trigeminal deafferentation in the rabbit.
Bilateral trigeminal deafferentation was performed in the rabbit in order to assess the role of orofacial inputs in regulation of the pattern of jaw movements during chewing. After bilateral combined section of the maxillary and inferior alveolar nerves, the animals did not eat food by themselves in the first postoperative week. However, they could chew and swallow when food was inserted into the mouth by an experimenter. The pattern of jaw movements and associated EMG activities of masticatory muscles during chewing were modulated remarkably by deafferentation. These modifications include 1) decrease in the horizontal excursions of the mandible at the power phase, 2) decrease in the maximum gape, 3) insufficient occlusion at the power phase (or increase in the minimum gape), 4) irregular patterns of jaw movements, 5) facilitation of the chewing rate, 6) increase in the number of chewing cycles in a masticatory sequence (the process from acceptance of food to swallowing), and 7) decrease in jaw-closing muscle activities. The findings indicate that deafferentation of the trigeminal sensory branches reduced masticatory force. On the other hand, no significant change was seen in the animals with disruption of cutaneous sensations of the face due to bilateral section of the infraorbital and mental nerves. Intraoral sensations rather than extraoral sensations may thus be important for regulation of masticatory force and jaw movements during chewing. Jaw movements during chewing were also analyzed in the animals with either bilateral ablation of the cortical masticatory area (CMA) or bilateral lesion of the ventral posteromedial nucleus (VPM) of the thalamus in order to examine whether profound effects of trigeminal deafferentation are produced via the transcortical loop. The animals with lesion of either the CMA or VPM demonstrated disturbances in feeding behavior, including the dropping of ingested food from the mouth, elongation of a masticatory process, reduction in the chewing efficiency, etc. However, the pattern of jaw movements during chewing were essentially similar to that in the preoperative period. These results do not necessarily deny a contribution of the CMA to regulation of jaw movements but suggest that the transcortical feedback loop via the CMA and thalamic VPM nucleus would not primarily be responsible for pattern formation of jaw movements during chewing in the rabbit. Probably, the sensory feedback via the transcortical loop may indirectly facilitate activities of the brain stem CPG, which facilitates the chewing rhythm or enables masticatory sequences to be conducted smoothly.
Afferent Pathways↗
Sensory components facilitating jaw-closing muscle activities in the rabbit.
The role of oral and facial sensory receptors in the control of masticatory muscle activities was assessed from the effect of acute deafferentiation on cortically induced rhythmic jaw movements (CRJMs) in anesthetized rabbits. When a thin polyurethane-foam strip (1.5, 2.5 or 3.5 mm thick) was placed between opposing molars during CRJMs, masseteric activities were facilitated in association with an increase in the medial excursion of the mandible during the power phase. The effects varied with the pattern of CRJMs, and the rate of facilitation was greater for small circular movements than for the crescent-shaped movements. Furthermore, the response of the masseter muscle was greater in the anterior half of the muscle, where muscle spindles are most dense, than in its posterior half. It was also demonstrated that the response increased with an increase in the thickness of the test strip. In contrast, the activities of the jaw-opening muscle were not affected significantly. The duration of masseteric bursts increased during application of the test strip and the chewing rhythm tended to slow down. However, the latter effect was not significant. After locally anesthetizing the maxillary and inferior alveolar nerves, the facilitative responses of the masseter muscle to the test strip was greatly reduced but not completely abolished. Lesioning of the mesencephalic trigeminal nucleus (Mes V) where the primary ganglion cells of muscle spindle afferents from jaw-closing muscles and some periodontal afferents are located, also reduced the facilitative effects. Similar results were obtained in the animals with the kainic acid injections into the Mes V 1 week before electrical lesioning of this nucleus. In these animals the effects of electrical lesioning of the Mes V could be attributed to the loss of muscle receptor afferents since the neurons in the vicinity of the Mes V were destroyed and replaced by glial cells, whereas the Mes V neurons are resistant to kainic acid. When electrical lesioning of the Mes V and sectioning of the maxillary and inferior alveolar nerves were combined in animals with a kainic acid injection into the Mes V, the response of the masseter muscle to application of the strip was almost completely abolished. From these findings, we conclude that both periodontal receptors and muscle spindles are primarily responsible for the facilitation of jaw-closing muscle activities.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Influence of hypoxia on mitochondrial function and energy status in CCl4-induced cirrhotic rat liver.
The influence of hypoxia on hepatic mitochondrial function and energy status was studied in normal and carbon tetrachloride (CCl4)-induced cirrhotic rats. Under hypoxemia of 50 mm Hg-PaO2, hepatic energy status was suppressed both in normal and cirrhotic rats. After the reversal of hypoxia, it was completely restored in normal rats concomitant with a rapid elevation of hepatic mitochondrial redox state (overshoot phenomenon) and increase in the mitochondrial oxidative phosphorylative activity. By contrast, in cirrhotic rats, such an enhancement of mitochondrial function was not observed. It was clarified that cirrhotic liver mitochondrial function was not observed. It was clarified that cirrhotic liver mitochondria have little capacity to respond to the hypoxic stress. A lower resistance to hypoxic episode in cirrhotics might be attributable to the absence of mitochondrial enhancement which is a compensatory mechanism for the deranged energy metabolism of the liver.
Animals↗
Mass screening for breast cancer: comparison of the clinical stages and prognosis of breast cancer detected by mass screening and in out-patient clinics.
To establish the criteria for assessing the life-prolonging effect of mass screening for breast cancer, clinical stage and prognosis of breast cancer detected by mass screening in 11 regions of Japan were compared with those for matched patients in out-patient clinics. A total of 728 patients detected by mass screening and 1,450 found in the out-patient clinics were reviewed. The stage of the disease was Tis or I in 40.9% of the patients detected by mass screening, and 28.7% of those found in the out-patient clinics. In contrast, stage III was found in 9.3% and 14.6%, respectively, indicating that early stages were significantly more common in the patients detected by mass screening. The overall survival curve for the patients detected by mass screening was compared with that for those found in the out-patient clinics. The 5-year survival rate was significantly higher in the patients detected by mass screening (91.7% vs. 85.6%; P less than 0.01), while the 10-year survival rate was slightly higher in the same group of patients, but the difference from the other group was not significant (80.5% vs. 78.1%). Women who had conducted breast self-examination (BSE) showed a higher survival rate than those who had not conducted BSE.
Breast Neoplasms↗
Plasma adsorption using bilirubin-adsorbent materials as a treatment for patients with hepatic failure.
In order to achieve a higher degree of improvement in patients with postoperative hepatic failure, the effects of plasma adsorption (PA) using a serial connection of noncoated charcoal (N 350) and a new bilirubin adsorbent material, styrenedivinylbenzene (BR350), were investigated both experimentally and clinically. After in vitro perfusion of high bilirubin containing plasma through these columns for 3 hours, total bilirubin levels were drastically reduced to 21% of the preperfusion level in the serial connection of N 350 and BR 350, while it remained high at over 40% in the single use of each column. Total branched chain and aromatic amino acid levels were also drastically reduced in the serial connection of these columns to 50, 40, and 7%, respectively, while the total amino acid levels remained high at 87% in the single use of BR 350. The combination of these columns enhanced rather than interfered with one another. Patients who received this treatment achieved an initial reduction of plasma total bilirubin and aromatic amino acids of 57 +/- 6 and 84 +/- 7, respectively. Although the long-term prognosis for these patients was negative, improvement of clinical and laboratory findings were actually obtained by this treatment. This PA system could provide a possibility for an improved supportive therapy for hepatic failure, especially for patients with hepatic coma and hyperbilirubinemia.
Adsorption↗
Effect of ANP on circulating blood volume.
The effects of rat atrial natriuretic peptide (rANP) on blood volume (BV) were determined by the continuous measurement of BV, mean arterial pressure (MAP), and central venous pressure (CVP). Immediately after a single-bolus injection of rANP-(1-28), 1 nmol/100 g body wt, in conscious rats, BV began to decrease. Peak reduction of -0.22 +/- 0.03 ml/100 g body wt was reached 14.5 min after the injection. Thereafter, BV levels returned gradually to -0.08 +/- 0.03 ml/100 g body wt compared with the control value. In volume expansion experiment, the nephrectomized, anesthetized rats were divided into two groups: the control group, with only a saline infusion, and the ANP group, with an infusion of saline with rANP (1 nmol/100 g body wt). In the ANP group, increases in BV were not as great, and recovery was threefold faster than that of the control group. In the ANP group, the recovery time of BV to the starting control levels was 8.5 min, and the time constant of recovery was 3.6 +/- 0.3 min-1. The control group times were 25 min and 11.5 +/- 0.8 min-1, respectively. The effective vascular compliances were approximately 2.8 ml.mmHg-1.kg body wt-1 in both groups, and the capillary filtration coefficient was 0.47 ml.mmHg-1.min-1.kg body wt-1 in the ANP group and 0.33 ml.mmHg-1.min-1.kg body wt-1 in the control group. Thus the whole body capillary filtration coefficient was 1.5-fold higher in the ANP group than in the control group. This suggests that ANP may increase the permeability of capillaries.
Animals↗
[Neuroleptic properties of Y-20024, a new benzofurancarboxamide derivative].
N-[(1-butyl-2-pyrrolidinyl)methyl]-2-methyl-5-sulfamoyl-2,3- dihydrobenzofuran-7-carboxamide hydrochloride (Y-20024) was synthesized in our laboratories in anticipation of developing a new psychotropic drug. In the present study, the pharmacological properties of Y-20024 were compared with those of sulpiride (SPR) and haloperidol (HPD). Administered orally, Y-20024 was 10 times stronger than SPR in inhibiting apomorphine (0.5 mg/kg, s.c.)-induced hyperactivity in mice; administered intravenously or intracerebroventricularly, it was 2 times or one third as strong, respectively. Y-20024 was almost equipotent to SPR in antagonizing apomorphine (0.1 mg/kg, s.c.)-induced vomiting in dogs. Combined with methamphetamine (5 mg/kg, i.p.), Y-20024 and SPR induced mortality dose-dependently in rats, but HPD did not. The mammotropic activity of Y-20024 administered orally once a day for 5 days was almost equipotent to that of SPR. From these results, Y-20024, pharmacologically similar to SPR, but superior in bioavailability and penetration through the blood brain barrier, may have potential usefulness as an antipsychotic drug.
Animals↗
Neural substrates for reflex salivation induced by taste, mechanical, and thermal stimulation of the oral region in decerebrate rats.
In order to investigate the neural mechanisms of reflex salivary secretion, experiments were carried out on anesthetized, decerebrate rats from which the volumes of submandibular salivary secretion and the efferent discharges in the preganglionic parasymapathetic fibers innervating the submandibular gland were recorded. Salivary secretion was induced by either infusing a taste solution, or an aliquot of hot water (45-55 degrees C) into the oral cavity, or by pinching the frontal parts of the oral region with a pair of forceps. The reflex salivation induced by noxious thermal and mechanical stimuli was markedly reduced by lesioning either the caudal (VC), or the interpolar (VI) trigeminal sensory nuclei. Taste-elicited salivary secretion was significantly reduced by lesioning the nucleus of the tractus solitarius (NTS). Of 43 preganglionic parasympathetic fibers sampled, 27 responded to both noxious mechanical and thermal stimulation of the oral region, and to electrical stimulation of the VC. Ten fibers responded only to taste stimulation and to electrical stimulation of the NTS. The remaining 6 fibers responded to both taste and noxious thermal stimulation of the oral region. These fibers responded well to NTS stimulation, but gave only a slight response to VC stimulation. These results suggest that two distinct neural pathways exist which mediate reflex salivation in the lower brain stem of the rat, i.e., the taste pathway via the NTS and the nociceptive pathway via the trigeminal sensory nuclei.
Animals↗
Blood levels of FK506 after intramuscular and intravenous administration in dogs.
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Animals↗