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Biomedical subjects

K Sumimoto

Publications and source records attributed to K Sumimoto.

At least 19 recordsLinked to original sources

Regulatory effect of aminopeptidase inhibitor (bestatin) on the cervix during induction of ripening by interleukin-8.

Bestatin is an immunomodulatory peptide that stimulates the humoral and cell-mediated immune system. It also has an inhibitory effect on multiple aminopeptidases. Recently we found that aminopeptidase N inactivates interleukin-8 in vitro. Bestatin successfully suppresses the effect of aminopeptidase N on interleukin-8. During cervical maturation many biochemical changes occur including decrease in collagen concentration and increase in collagenase and elastase activities. Interleukin-8, which has a potent neutrophil chemotactic effect, was found to induce cervical ripening in rabbits. The combination of interleukin-8 with bestatin also induced cervical ripening by providing approximately regular levels of neutrophil numbers, collagenase, and elastase activities. We therefore suggest that this regulatory mechanism also takes place in vivo through the inhibitory effect of bestatin on aminopeptidase N.

Animals

The effect of interleukin-1 in rabbit cervical ripening.

OBJECTIVE: In this research we studied the effect of interleukin-1 beta (IL-1 beta) on the cervix. STUDY DESIGN: Vaginal suppositories of a low dose of IL-1 beta (200 ng) were applied to non-pregnant and pregnant rabbits. Results were compared with a control group which were treated only by placebo. Water concentration, collagen content, collagenase and elastase activities were measured. Neutrophil numbers in the cervical connective tissue were counted. Also, interleukin-8 (IL-8) was measured in the supernatant of homogenized cervical tissue treated by IL-1 beta. RESULTS: Water contents of the tested cervices were increased (P < 0.006 and 0.03, respectively), whereas collagen content was markedly decreased (P < 0.0004 and 0.001, respectively). Collagenase activity was found to be increased in non-pregnant and pregnant cervices treated by IL-1 beta (P < 0.02 and 0.002, respectively). Also, elastase activity of these cervices were significantly increased compared to the control group (P < 0.0007 and 0.001, respectively). Neutrophil invasion was observed in the cervical connective tissues after application of IL-1 beta. IL-8 was significantly elevated (P < 0.0001) in the treated cervices. CONCLUSION: Interaction between IL-1 and IL-8 is suspected to be essential for cervical ripening.

Animals

Eclampsia-like seizures and electroencephalographic changes in pregnant rabbits with endothelin-1 injections.

To examine the possible role of endothelin and vasospasm in eclamptic seizures, we studied and analyzed the electroencephalograms (EEG) of endothelin-1 (ET-1)-treated pregnant, nonpregnant and sham control (dextrose-treated) rabbits. After multiple intravenous bolus injections of ET-1 (500 pmol/kg) or 5% dextrose in the rabbits, we recorded EEG directly from the brain cortex and analyzed by Fast Fourier Transform (FFT). Water content was measured in the brain of all groups (n = 7). Repeated seizures occurred in all of the pregnant and 2 of the nonpregnant rabbits by variable doses of ET-1. FFT analysis showed remarkable changes in frequency and power arrays characterized by mild to severe form of dysrhythmia, high-voltage spikes, high-voltage fast and slow waves after ET-1 injections. Water content was increased in brain mass in ET-1-treated rabbits (p = 0.001) suggesting an ET-1-induced edema. Histologically we confirmed that ET-1 caused ischemic changes in brain tissues. However, ET-1 induced more pronounced changes in behavior, EEG, brain edema or ischemia in pregnant than in nonpregnant groups. The injections of exogenous ET-1 into the brain substances were strongly suggested by immunohistochemical study with polyclonal antiendothelin antibody in brain tissue sections. Therefore, we assume that endothelin along with other vasoactive substances causes acute cerebral vasospasm and ischemia inducing EEG changes leading to ultimate clinical convulsions in eclampsia.

Animals

Effects of neutrophil chemotactic factors on cervical ripening.

Our aim was to study the effects of infection mediated by bacterial endotoxins (lipopolysaccharides LPS) and bacterial substrate (N-formyl-methionyl-leucyl-phenylalanine FMLP) on pathological cervical ripening, and compare their effects with the normal physiological mediator interleukin-8 (IL-8). Twenty non-pregnant rabbits were treated vaginally either by placebo, LPS, FMLP or IL-8 for 3 successive days. Water concentration was measured. Neutrophils were counted in 5 random fields of each specimen. Collagen and glycosaminoglycan concentrations were assessed histologically by using picrosirius red and alcian blue staining and optical density was calculated. LPS FMLP as well as IL-8 can induce cervical ripening. Water concentration was found to be significantly increased in these groups (p < 0.0001). Also, significant numbers of neutrophils were found to accumulate in the connective tissue of these cervices (p < 0.0001). Collagen concentration was significantly decreased in the cervices treated by LPS, FMLP and IL-8 (p < 0.0001). Glycosaminoglycan concentration was significantly increased in cervices treated by LPS, FMLI as well as IL-8 (p < 0.0001, 0.006 and 0.001 respectively). LPS, FMLP and IL-8 stimulate cervical ripening in non-pregnant rabbits. This ripening was mediated through the accumulated neutrophils in the connective tissue. IL-8 has a physiological type effect to induce ripening of the cervix.

Animals

The significance of bile secretion after the transplantation of long-preserved livers in the rat.

Although one of the simplest indicators for predicting liver viability is bile secretion, it has never been proven whether it could be a good index for the viability of grafts in liver transplantation after cold ischemia. The present study, conducted on male Wistar rats, was undertaken to determine whether bile secretion reflects the viability of livers which have been preserved long-term. Livers were stored for up to 24 h in Euro-Collins (EC) or University of Wisconsin (UW) solution at 4 degrees C, and transplanted orthotopically. The correlation between 1-week survival, bile flow, and the tissue adenosine triphosphate (ATP) level 4 h after transplantation was then investigated for each subgroup. The survival rates of the animals in the UW subgroups were much higher than those in the EC subgroups. In the rats transplanted with livers preserved for 6 h in EC solution (EC-6), in which 100% survival was observed, both bile flow and ATP recovered sufficiently. Conversely, in the EC-12 group, in which only 10% survival was seen, restoration of bile flow, in ml/h per kg body weight, and ATP resynthesis, in mumol/g wet weight, were severely suppressed, with levels of 1.35 +/- 1.05 and 0.77 +/- 0.34, respectively. Moreover, in the EC-18 group, with 0% survival, neither bile flow nor ATP recovered. In the rats transplanted with livers preserved for 18 h in UW solution (UW-18), bile flow and ATP, being 1.03 +/- 0.56 and 1.12 +/- 0.59, respectively, were much higher than those in the EC-18 group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine

Interleukin-8 induces cervical ripening in rabbits.

OBJECTIVE: The purpose of this study was to determine whether cervical ripening can be induced in rabbits by interleukin-8. STUDY DESIGN: Nonpregnant and pregnant rabbits were treated for 5 days with vaginal suppositories containing 100 ng of interleukin-8. Collagen and glycosaminoglycan concentration in the cervices were assessed histologically by picrosirius red and alcian blue, and the mean optical density was calculated. The mean neutrophil count in five random fields was calculated from each biopsy specimen. RESULTS: Interleukin-8 induced softening and dilatation of the rabbit cervices. Water content was significantly increased (p < 0.0001 and p < 0.001, respectively). Cervical collagen concentration was found to be significantly decreased (p < 0.0004 and p < 0.0001, respectively). Glycosaminoglycan concentration was significantly increased in nonpregnant and pregnant cervices (p < 0.0009 and p < 0.1, respectively). The mean number of neutrophils was significantly increased (p < 0.0005 and p < 0.006, respectively). CONCLUSION: Interleukin-8 can induce cervical ripening in nonpregnant and pregnant rabbits.

Animals

Suppression of liver allograft rejection by administration of 15-deoxyspergualin. Comparison of administration via the hepatic artery, portal vein, or systemic circulation.

In this experiment, the effect of the administration route-the hepatic artery, portal vein, or systemic circulation-of the immunosuppressive drug 15-deoxyspergualin (DSG) on the suppression of liver allograft rejection is investigated. A 3-day injection of DSG at a dose of 0.32-1.28 mg/kg per day into the systemic circulation of a rat that had received a liver transplant was not effective in prolonging liver graft survival (14.3 +/- 2.9 days vs. 14.1 +/- 2.5 days for controls). However, the administration of DSG into the portal vein following liver transplantation markedly prolonged survival for up to 24.9 +/- 10.0 days. Survival times were prolonged even more when the DSG was administered via the hepatic artery for 3 successive days after liver grafting (30.9 +/- 9.6 days). The concentration of DSG in the blood following the one-shot injection of DSG was highest when DSG was administered via the hepatic artery, intermediate when injected into the portal vein, and lowest when injected into the systemic vein. In conclusion, DSG can inhibit liver graft rejection more effectively via the hepatic arterial route than via the portal vein or systemic circulation.

Animals

A comparison of some simplified lactobionate preservation solutions with standard UW solution and Eurocollins solution for pancreas preservation.

Fifty-two rat pancreas transplants were performed to investigate which components of the UW solution were essential for successful pancreas preservation. LEW rats were used and the pancreata stored at 4 degrees C for 48 hr after flushing with commercial UW solution (ViaSpan, DuPont Pharmaceuticals) or a number of simplified solutions. Following storage the pancreata were transplanted into syngeneic recipient animals with streptozotocin-induced diabetes mellitus. Graft function was assessed by regular postoperative blood sugar measurements and a glucose tolerance test on the 14th postoperative day. With commercial UW solution, 4 of 9 recipients (44%) showed satisfactory graft function, while only one of 5 pancreata preserved using Eurocollins solution demonstrated satisfactory function. With solution A, in which hydroxyethyl starch and insulin were omitted from the standard UW solution, 3 of 7 recipients (43%) showed satisfactory function. Omission of glutathione, allopurinol, and adenosine from this solution (solution B) gave satisfactory function in 4 of 8 cases (50%). Substitution of raffinose in solution B with an equimolar concentration of glucose (solution C) resulted in acceptable function in 5 of 8 cases (62%). Increasing the raffinose concentration in solution B to 100 mM/L resulted in only 2 of 8 grafts (25%) with adequate function. By contrast, reversing the Na/K concentrations in solution A resulted in 100% (7/7) satisfactory graft function. We conclude that the rat pancreas can be successfully transplanted following 48-hr cold preservation using UW solution and some simplified versions, and that a substantially simplified lactobionate-based solution with a reversed sodium/potassium ratio improved survival.

Adenosine

An examination of the effects of solutions containing histidine and lactobionate for heart, pancreas, and liver preservation in the rat.

Fifty-five rat pancreas transplants, 18 rat heart transplants, and 41 rat liver transplants were performed using standard UW solution, the new HL solution (HL-I), or a modified HL solution (HL-II). Storage times of 18 hr were used in the heart preservation experiments, 24 hr in the liver preservation experiments, and 48 or 72 hr in the pancreas preservation experiments. HL-I solution was superior to both HL-II and UW solution for heart preservation (1-week graft survival rates of 100% [7/7], 0% [0/5], and 50% [3/6], respectively). HL-I and HL-II were superior to UW for 24 hr liver preservation (1-week graft survival rates of 78% [11/14], 80% [8/10], and 29% [5/17], respectively). In contrast, HL-II was superior to both HL-I and UW solutions for pancreas preservation following both 48-hr preservation and 72-hr preservation. Satisfactory graft function was achieved in 100% (7/7), 40% (6/15), and 44.4% (4/9) of pancreases transplanted after 48 hr using HL-II, HL-I, and UW solutions, respectively, and in 50% (4/8), 0% (0/8), and 0% (0/8) following 72-hr preservation. Histidine- and lactobionate-containing solutions thus represent a further improvement in organ preservation by simple cold storage.

Adenosine

A comparison study of rat pancreas preservation using perfluorochemical and fluorocarbon-emulsion as preservation medium.

We reported previously the successful 72-hour cold rat pancreas preservation by using Perfluorochemical (PFC). The present study is to determine whether Fluorocarbon (FC) emulsion is as effective as PFC for long-term rat pancreas preservation. Lewis rat pancreases were stored in FC emulsion (4 degrees C) saturated by continuous supply of oxygen:carbon dioxide (95%:5%) (Group I) or by 100% pure nitrogen (Group II), or in PFC (4 degrees C) saturated by continuous supply of oxygen:carbon dioxide (95%:5%) (Group III) or nitrogen (Group IV) for 24 h and 48 h. Heterotopic pancreas transplantation into isogeneic diabetic rats were performed following preservation. Functional graft success rates following 24 h and 48 h cold storage were 71% (5/7) and 0% (0/5) in Group I, 71% (5/7) and 0% (0/5) in Group II, 100% (5/5) and 80% (4/5) in Group III, and 80% (4/5) and 0% (0/5) in Group IV, respectively. These results showed that, as an artificial blood substitute, the PFC with simple oxygen bubbling for 48-hour preservation of rat pancreas was much effective than FC emulsion, but not effective when saturated with nitrogen. We concluded that the PFC with saturated oxygen can obtain long-term successful preservation of rat pancreas. The direct oxygenation of the graft tissues is thought to play an important role in organ preservation.

Animals

[Field trial for the early detection of patients with ovarian cancer--discrimination of ovarian cancer patients by the statistical analysis using Mahalanobis' generalized distance].

Six tumor-associated antigens, cancer antigen 125 (CA125), tissue polypeptide antigen (TPA), ferritin (Fr), carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), and sialyl Lex-i (SLX) were measured simultaneously for the early detection of ovarian cancer. To decrease the number of both false positive and false negative cases in the combination assay, statistical discrimination analysis employing the serum values for appropriate tumor markers has been studied with respect to ovarian cancer by the method of Mahalanobis' generalized distance. The new "ovarian cancer screening test" designed by us has been used in Shizuoka Prefecture since 1988, and 23,307 serum samples have been analyzed. One hundred twenty-seven of 165 ovarian cancer patients were suspected as having cancer by such clinical procedures as pelvic examination and/or ultrasonography, while in 150 patients cancer was detected by the statistical discrimination method. Thirty-one of 38 patients with ovarian cancer overlooked by the clinical procedures could be found by the statistical method. We conclude that clinical procedures and the statistical method can be complementary in detecting patients with this malignancy.

Adult

Clinical use of synthetic absorbable cuff material for peripheral vascular anastomosis.

End to end arteriovenous (AV) fistulas were created using the cuff technique for hemodialysis in 12 patients with end stage renal disease. The cuff used was made of a synthetic biodegradable material, a lactic glycolic acid co-polymer with the same composition as absorbable surgical suture. Cephalic vein radial artery fistulas in the forearm were created electively in six patients to convert a Scribner shunt to a fistula in three patients and because of malfunction of a fistula created previously in three patients. Eleven patients underwent hemodialysis, with pump speeds of more than 200 milliliters per minute, and were evaluated for 129 to 477 days. These subcutaneous AV fistulas were maintained as patent functional veins and continued to function without complication. After five weeks, one patient had conversion to a prosthetic AV fistula because of poor venous maturation. The overall patency rate was 92 percent. The diameter of the AV anastomosis increased gradually with time. At 20 weeks, however, it reached more than 70 percent of the diameter of the radial artery lumen. These observations led us to believe that the cuff material used is biodegraded until 20 weeks and gives sufficient flexibility. In the future, the cuff method is expected to be clinically developed as another approach for vascular anastomosis.

Adult

Determining zinc coproporphyrin in maternal plasma--a new method for diagnosing amniotic fluid embolism.

We measured the concentration of zinc coproporphyrin I (ZnCP-I), a characteristic component of meconium, in maternal plasma by fluorometry after HPLC. We obtained plasma samples from 89 women: 35 at weeks 10-40 of normal pregnancy, 41 shortly after normal delivery, 4 from patients with amniotic fluid embolism (AFE), and 9 from non-AFE patients with intra- or postpartum shock caused by genital bleeding. The plasma ZnCP-I concentration was 97 (SD 83, range 38-240) nmol/L in the AFE patients, 11 (SD 9.2) nmol/L in the non-AFE patients, 12 (SD 7.9) nmol/L during normal pregnancy, and 26 (SD 10) nmol/L shortly after normal delivery. We suggest that measuring ZnCP-I in maternal plasma by fluorometry on HPLC is a rapid, noninvasive, and sensitive method for diagnosing AFE and propose 35 nmol/L as the cutoff value for the ZnCP-I concentration in maternal plasma for the diagnosis of AFE.

Adult