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Biomedical subjects

T Morimoto

Publications and source records attributed to T Morimoto.

At least 505 records · Page 28Linked to original sources

Attenuation of ischemia-induced regional myocardial acidosis by LP-805, a newly developed vasodilator, in dogs.

The effect of 8-tert-butyl-6,7-dihydropyrrolo[3,2-e]-5-methyl- pyrazolo[1,5-a]pyrimidine-3-carbonitrile (LP-805), a newly developed vasodilator, on myocardial acidosis induced by ischemia was studied in anesthetized open-chest dogs. Ischemia was induced by partially occluding the left anterior descending coronary artery. The coronary flow was artificially reduced to about 1/3 of the original flow. Myocardial pH was measured with a glass micro pH electrode inserted into the left ventricular wall perfused by the occluded artery. Myocardial pH decreased from about 7.5 to about 6.9 after the onset of ischemia and remained at this low level until the occluded coronary artery was released. After 30 min of ischemia, either saline containing 0.1 N HCl or 10, 30 or 100 micrograms/kg of LP-805 was injected intravenously. LP-805 attenuated the decrease in myocardial pH induced by ischemia in a dose-dependent manner. In conclusion, LP-805 may reduce the influence of ischemia on the myocardium.

Acidosis↗

Comparison of estrogen receptor and epidermal growth factor receptor content of primary and involved nodes in human breast cancer.

Estrogen receptors (ER) and epidermal growth factor receptors (EGFR) in the tumor cells of breast cancer tissues (primary tumors) and metastatic lymph nodes (involved nodes) were analyzed by immunocytochemical study in 19 patients; 12 were ER positive, and seven were ER negative. Microscopic study was used to determine the percentage of positive cells and the staining index. The percentage of EGFR-positive cells and the EGFR staining index were higher in the ER-negative primary tumors than ER-positive primary tumors. In ER-positive cases, both the number of ER-positive cells and ER content per cell was less in the involved nodes than in the primary tumors, whereas the number of EGFR-positive cells and EGFR content per cell was greater in affected nodes. On the other hand, in the ER-negative cases the number of EGFR-positive cells and EGFR content per cell remain almost unchanged between the primary tumors and involved nodes. The authors supposed a probability, in this study, that estrogen may exert inhibitory action on EGFR production through binding to ER.

Adult↗

Pseudomonas aeruginosa alkaline proteinase might share a biological function with plasmin.

Pseudomonas aeruginosa alkaline proteinase, which is a zinc-dependent bacterial endopeptidase, preferentially hydrolyzed Boc-Val-Leu-Lys-methylcoumarylamide (MCA) which was originally designed as a specific substrate of plasmin, a plasma serine proteinase. The hydrolytic capacity was resistant to tosyl-lysine chloromethylketone at a concentration as high as 1 mM, but was blocked by a treatment with metal chelator such as o-phenanthroline at the concentration of 5 mM. Kinetic parameters of the amidolytic reaction were Km = 21 microM, kcat = 0.067 s-1 and kcat/Km = 3190 M-1 s-1. A synthetic peptide inhibitor which bore a possible ligand for zinc atom at the carboxy terminal was designed. This inhibitor, Ac-Val-Leu-Lys-4-mercaptoanilide, blocked the amidolytic activity of the pseudomonal alkaline proteinase in a competitive manner with the dissociation constant (Ki) value of 24 microM. The results imply that P. aeruginosa alkaline proteinase must be an unusual zinc-dependent 'C (COOH)-type' endopeptidase, which hydrolyzes the peptide bond of certain amino acid residues at the carboxyl group side by specific recognition, like serine- and cysteine-proteinases. In comparison, P. aeruginosa elastase which is a typical 'N (NH2)-type' metalloproteinase did not hydrolyze all of the commercially available peptide-MCA substrates tested at the present study. P. aeruginosa alkaline proteinase also hydrolyzed natural substrates of plasmin, such as fibrin and fibrinogen, with similar specific activities to plasmin. The susceptible subunits of fibrinogen were the A-alpha and B-beta ones, in this order. P. aeruginosa alkaline proteinase also exhibited an anti-coagulant activity in human plasma attributed to the direct fibrinogenolytic function. Such potential anti-coagulant capacity of the P. aeruginosa alkaline proteinase might explain, at least partly, the most characteristic pathologic feature of the P. aeruginosa septicemia, hemorrhagic lesions with lacking thrombi (Fetzer, A.E. et al. (1967) Am. Rev. Respirat. Dis. 96, 1121-1130).

Blood Coagulation↗

Correlation between estrogen receptor status and histological malignancy in human breast cancer.

Sixty-two breast carcinoma patients underwent mastectomy and were analyzed for correlations between estrogen receptor (ER) status of the tumor and the histological findings of tumor, age, nodal status, and tumor size. An immunocytochemical assay for the detection of ER in breast carcinomas was used to evaluate the staining intensity index (SII) of the ER level of the tumors, which was calculated from the staining intensity of cancer cells and the percentage of ER-positive cancer cells. The histological differentiation of carcinomas showed a strong correlation with the SII. A statistically significant (F = 10.580, P less than 0.0005) negative correlation was found between the grade of malignancy and the SII. Patients under 50 years of age tended to have a lower SII, whereas patients over 49 years of age tended to have a higher SII. The tumor size, and nodal status showed no correlations with the SII in any of the patients. The histological differentiation of the tumor cells showed a strong correlation with the heterogeneity of the distribution of ER-positive cells in breast cancers.

Adult↗

Carotid bifurcation reconstruction using y-shaped microvascular grafts: an experimental study in rats.

Reconstruction of the carotid bifurcation was performed in rats using y-shaped microvascular grafts in an attempt to examine the feasibility of using such grafts in intracranial vascular reconstruction, especially for vessels with bifurcations. Twenty y-shaped microarterial grafts were obtained from the carotid bifurcation of donor rats, while 20 y-shaped microvenous grafts were obtained from the femoral veins of the rats. The patency rate of arterial grafts and venous grafts were 75% and 97%, respectively. Anastomotic aneurysms frequently occurred in both arterial grafts (45%) and venous grafts (60%). Results of histological examinations concluded that these aneurysms were false aneurysms. We discuss the reasons for aneurysm formation and technical issues that might improve the experimental results with regard to patency and aneurysm formation.

Anastomosis, Surgical↗

Clinical course and long-term prognosis of Japanese patients with ulcerative colitis.

The course and prognosis of 308 patients with ulcerative colitis who visited Tohoku University Hospital during the period from 1954 to 1987 were investigated. Based these investigations, the following results were obtained. 1) In 27.6% of patients with proctitis, extension to the proximal colon developed during the observation period. 2) Surgical intervention was necessary in 33.9% of patients with total colitis and in 9.7% of those with left-sided colitis. 3) Of 1,566 patient-years in which the course was observed, 988 (63.1%) were active-years. When the course of ulcerative colitis was analyzed according to the duration and extent of involvement, the frequency of the attack-years in patients with proctitis or left-sided colitis steadily decreased with time. However, that of total colitis was constant, 65-85%, regardless of the follow-up period. Patients younger than age 20 at onset were prone to relapse during their course, compared with patients older than 20. 4) Ten patients died from causes related to ulcerative colitis in our hospital: 5 of them due to postoperative complications. Two patients developed colorectal cancer accompanying ulcerative colitis. 5) With respect to the cumulative survival rate, the 95% confidence limits of the observed curve was lower than the expected curve during the first 2 years and 12-16 years after the onset. The main causes of death were postoperative complications in the former and unrelated deaths of older patients in the latter.

Adult↗

Local cerebral blood flow with prostaglandin E1 or trimethaphan during cerebral aneurysm clip ligation.

This study was performed to examine changes in local cerebral blood flow during hypotensive anaesthesia with either prostaglandin E1 (PGE1) or trimethaphan (TMP). Local cerebral blood flow (LCBF), mean blood pressure (MBP), heart rate (HR), and hourly urine output (UO) were studied in 51 patients undergoing cerebral aneurysm surgery with neuroleptanalgesia (NLA). The incidence of vasospasm after aneurysm surgery, and outcome (Glasgow Outcome Scale) at discharge were evaluated. Measurements of LCBF were made using a thermal gradient blood flow meter. The dose of PGE1 or TMP was adjusted to maintain MBP at about 70 mmHg, and LCBF was studied during and after PGE1 or TMP administration. Hypotensive drugs were discontinued at the completion of aneurysm clipping. After starting PGE1 or TMP, MBP decreased immediately, but HR did not change in either group. The LCBF decreased 30 min after the start of TMP administration and increased immediately after its discontinuation, whereas PGE1 did not affect LCBF. Urine output increased during PGE1 administration but was unchanged during TMP. Neither drug affected surgical outcome or the incidence of vasospasm. These results suggest that PGE1 may be preferable to trimethaphan for hypotensive anaesthesia in cerebral aneurysm surgery because LCBF is maintained.

Adult↗

Changes in facial skin temperature associated with chewing efforts in man: a thermographic evaluation.

Eleven healthy male adults chewed hard and soft chewing-gums for 5 min. A thermographic record of the face on the chewing side was made at the beginning of, during and after the effort. Facial temperature distributions during open/close cyclic unloaded jaw movements were recorded at a later date. The dimensions of the zones whose temperatures were 1.4 degrees C or more higher than the central temperature during the experiment were determined. There was a linear increase in the dimensions of these zones after the chewing. In contrast, the cyclic jaw movements did not result in significant increases. Chewing the hard gum produced significantly higher temperature rises than did the soft in the masseter area. After the chewing effort, the temperature fell gradually, but did not return to the initial state even after 30 min. The overall decreasing pattern of the temperature distribution for chewing the soft gum was similar to that for the hard gum. The facial temperature associated with chewing efforts rose in accordance with the resistance offered by the chewing-gums.

Adult↗

The morphologic feature of mucus leakage appearing in low papillary carcinoma of the breast.

This report summarizes the clinicopathologic findings in 11 cases of low papillary carcinoma of the breast accompanied by the morphologic feature of mucus leakage into the mammary stroma. These cases were characterized by two morphologic findings. First, abundant mucus produced by the tumor cells filled the intraductal spaces where neoplastic epithelium formed very low papillary projections, ie, a feature of mucinous-producing low papillary carcinoma in situ. Second, there was expansive leakage of mucus into the mammary stroma occasionally accompanied by a few epithelial cells. All the cases showed a high level of mucus production and contained no elements of invasive ductal carcinoma or ordinary invasive mucinous carcinoma. These cases have no evidence of direct invasion of the mammary stroma by malignant cells. The average age of the 11 patients was 41 years. Foci of microcalcification were seen in some tumors (seven cases; 64%). There were no cases with lymph node metastases. All the patients underwent mastectomy with no adjuvant therapy, and they are currently alive and well.

Adenocarcinoma, Mucinous↗

An autopsy case of I-cell disease. Ultrastructural and biochemical analyses.

An autopsy case of I-cell disease in a 4-year-old Japanese girl is presented. In this report, the authors analyze the relationship between morphologic (including electron microscopic) and biochemical findings. Lymph node, spleen, and kidney, which were stained with Hale's colloidal iron method, contained large amounts of hexosamine. These substances had accumulated in lymphocytes of B-cell lineage.

Cadaver↗

The influence of the calcium antagonist nimodipine and induced hypertension on the behavior of the cerebral pial arteries, the blood-brain barrier, cerebral edema, and cerebral infarction in cats with one-hour occlusion of the middle cerebral artery.

Thirty anesthetized cats were randomly assigned to one of three groups of 10 cats each: nimodipine treatment, nimodipine treatment combined with induced hypertension, or a control group. The behavior of the cerebral pial arteries was measured by means of microscopic observation through a cranial window. The middle cerebral artery of each cat was clipped for 1 hour via the transorbital approach. Five hours after circulation was reestablished in the middle cerebral artery, Evans blue dye was injected intravenously: 30 minutes later, the animal was killed. Administration of nimodipine or saline in the treated or control group was started 5 minutes before the middle cerebral artery was clipped and maintained until the end of the experiment. Induced hypertension was produced by administration of dopamine during the occlusion. Damage to the blood-brain barrier (BBB) was judged by extravasation of Evans blue dye. Cerebral edema and infarction were evaluated from histological findings. They were most prominent in the control group: the extent of hemisphere affected was as follows (mean +/- standard error): extravasation, 40.5 +/- 8.8%; edema, 43.2 +/- 5.7%; infarction, 35.5 +/- 9.6%. On the other hand, the extravasation of Evans blue dye and cerebral edema were significantly more extensive in the group treated with nimodipine and induced hypertension (extravasation, 28.2 +/- 9.6% of the hemisphere; edema, 30.3 +/- 7.1%) than in the group treated with nimodipine alone (extravasation, 18.5 +/- 8.7% of the hemisphere; edema, 19.4 +/- 6.3%), but the infarction size was similar in both groups (16.6 +/- 4.9% of the hemisphere in the former; 17.0 +/- 6.2 in the latter).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Impairment of grafts by short-term warm ischemia in rat liver transplantation.

The mechanism of warm ischemic damage was investigated by assessing hepatic energy metabolism, mitochondrial functions, and lipid peroxidation (LP) of transplanted liver grafts in rats. Donor livers were stored ischemically either for 90 min at 4 degrees C (control) or for 20 min at 37 degrees C and 70 min at 4 degrees C (warm ischemia). In the control group, adenosine 5'-triphosphate (ATP) recovered within 8 min to 86% of the normal preischemic value (10.30, SEM 0.26 mumol/g dw). Total adenine nucleotides (TAN) recovered to 14.83 (SEM 0.22) mumol/g dw within 30 min, as compared with a normal level of 15.44 (SEM 0.36) mumol/g dw. The energy charge potential (ECP) immediately recovered to 0.79 (SEM 0.01) within 8 min (normal, 0.81, SEM 0.01). Mitochondrial phosphorylation rate (PR) was not significantly altered. LP averaged 451 (SEM 10) nmol/g dw in normal livers and did not change even during reperfusion (504, SEM 79, nmol/g dw, at 15 min). In contrast, in the warm ischemic group, ATP recovered only to 65% of the normal value even at 30 min (P less than 0.01), and TAN remained significantly lower than the control value (12.39, SEM 0.47, mumol/g dw, P less than 0.001). PR was normal at the end of warm ischemia, was significantly reduced at the end of the total ischemic period (P less than 0.001 and P less than 0.01, as compared with control and normal values, respectively), and gradually recovered over 30 min. LP increased and reached the maximum of 795 (SEM 84) nmol/g dw at 15-min reperfusion (P less than 0.05). In grafts treated with 50 mg/kg bw allopurinol (i.v.) 10 min prior to the onset of warm ischemia, ATP and ECP recovered to normal values at 30 min, and TAN was significantly higher than in the warm ischemic group (13.28, SEM 0.28, mumol/g dw, P less than 0.05). PR was maintained at normal values, and LP was increased but to a lesser degree than in the ischemic group. It is concluded that the delayed recovery of ATP metabolism in the warm ischemic group might be due to the loss of adenine nucleotides and the decreased PR, and that allopurinol has a protective effect against warm ischemic damage.

Allopurinol↗

Hemostatic alterations caused by ventricular assist devices for postcardiotomy heart failure.

The hemostatic alterations in two adult patients who were supported by left ventricular assist devices (LVADs) because of postcardiotomy heart failure were evaluated. In both patients, fibrinopeptide A and thrombin-antithrombin III complex increased markedly during the first several days, and thereafter decreased moderately but remained above normal over the entire procedure. Furthermore, fibrinopeptide B beta 15-42 and alpha 2 plasmin inhibitor-plasmin complex were also markedly increased over the entire course of LVAD treatment. These data show that the LVAD system strongly activates both the coagulation and the fibrinolytic system, even when thromboembolic or bleeding complications are not clinically evident. Furthermore, the decrease in physiological coagulation inhibitors, especially protein C, indicates that these factors are activated and consumed during LVAD treatment. Because protein C is important in regulating the coagulation cascade during LVAD treatment, exhaustion of this system might result in thromboembolic complications during LVAD treatment.

Aged↗

Vascular viscoelasticity of perfused rat hindquarters.

To determine viscoelastic features of the rat hindquarters vasculature, we measured pressure-volume curves. Male Wistar rats were transected at the lumbar level, and the perfused hindquarters were oxygenated with a hollow fiber artificial lung. The blood volume was measured by counting 51Cr-labeled red cells led to a gamma counter through an extracorporeal circuit at a constant rate. With continuous monitoring of the venous pressure and circulating blood volume, saline was infused into the circuit from a venous branch for 5 min [1.2 +/- 0.3% (SD) of tissue weight] followed by a 10-min recovery phase. In the recovery phase, the venous pressure promptly declined to the preinfusion level, whereas the circulating blood volume decreased more slowly. This implied vascular stress relaxation of the hindquarters. Maxwell's viscoelastic model, consisting of a spring component and a viscous component, was applied to analyze the venous pressure-volume diagram. With a curve-fitting method, the calculated vascular compliance and relaxation time (a time constant of stress relaxation) were 1.31 +/- 0.14 ml.mmHg-1.kg-1 and 15.7 +/- 4.0 min (means +/- SE), respectively. The value of compliance of the hindquarters was smaller than those of visceral organs reported. In addition, the value for relaxation time suggests that the viscous response of the vasculature simultaneously overlaps change in blood volume due to extravascular fluid shift during the postinfusion period.

Animals↗

Water and electrolyte balance in the vascular space during graded exercise in humans.

We analyzed the changes in water content and electrolyte concentrations in the vascular space during graded exercise of short duration. Six male volunteers exercised on a cycle ergometer at 20 degrees C (relative humidity = 30%) as exercise intensity was increased stepwise until voluntary exhaustion. Blood samples were collected at exercise intensities of 29, 56, 70, and 95% of maximum aerobic power (VO2max). A curvilinear relationship between exercise intensity and Na+ concentration in plasma ([Na+]p) was observed. [Na+]p significantly increased at 70% VO2max and at 95% VO2max was approximately 8 meq/kgH2O higher than control. The change in lactate concentration in plasma ([Lac-]p) was closely correlated with the change in [Na+]p (delta[Na+]p = 0.687 delta[Lac-]p + 1.79, r = 0.99). The change in [Lac-]p was also inversely correlated with the change in HCO3- concentration in plasma (delta[HCO3-]p = -0.761 delta[Lac-]p + 0.22, r = -1.00). At an exercise intensity of 95% VO2max, 60% of the increase in plasma osmolality (Posmol) was accounted for by an increase in [Na+]p. These results suggest that lactic acid released into the vascular space from active skeletal muscles reacts with [HCO3-]p to produce CO2 gas and Lac-. The data raise the intriguing notion that increase in [Na+]p during exercise may be caused by elevated Lac-.

Adult↗