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Biomedical subjects

T Maki

Publications and source records attributed to T Maki.

At least 127 records · Page 7Linked to original sources
PubMed1991

Successful treatment of diabetes with the biohybrid artificial pancreas in dogs.

We have investigated a new hybrid artificial pancreas device to transplant islet allografts without immunosuppression. The device consists of a chamber through which passes a copolymer membrane connected to standard vascular grafts. Islets are placed inside the chamber but are outside of the blood stream. Nominal molecular porosity of 80,000 daltons permits free diffusion of nutrients and insulin across the membrane but inhibits the entry of immunoglobulins and immunocytes from the blood stream into the chamber. Initial studies focused on the technical feasibility of implanting the unseeded (no islets) devices. In 12 normal mongrel dogs, the arterial limb of the device was anastomosed end-to-end to the common iliac artery and the venous limb end-to-side to the common iliac vein. Vascular patency was monitored by an audible bruit over the device. Two devices currently remain patent at 388 and 421 days. The remaining experiments failed due to thrombosis and membrane rupture, with 2 failing as late as 170 and 279 days. In a second series, both arterial and venous anastomoses were done end-to-side and dogs were placed on low-dose aspirin therapy. All 8 dogs are currently maintaining patent unseeded devices (96-226 days postimplantation). Subsequent studies determined the function of devices seeded with isolated canine pancreatic islet allografts in totally pancreatectomized, severely diabetic dogs. Diabetes was controlled by once-a-day insulin injection. After 2-3 weeks of diabetic control, a seeded device was implanted. Diabetic control was monitored by fasting blood levels and postprandial and intravenous glucose tolerance tests, and vascular patency by the loudness of the bruit. In the first series of 6 dogs given seeded devices without aspirin, no significant function was discernible, with failure attributable to thrombosis, poor islet viability, and surgical complications. In the second series of 13 dogs given aspirin, 8 dogs have required an appreciably lower dose of injected insulin to maintain fasting blood glucose at acceptable levels. Of note are 4 dogs that required virtually no exogenous insulin for at least 3 weeks. One dog lost function on day 74 and another still requires no insulin at 267 days postimplantation. However, despite normal fasting glucose levels, the glucose tolerance tests showed delayed return to normal levels. Weight lost following pancreatectomy was rapidly regained in the presence of a functioning seeded device. Histologic examination of the removed devices revealed no signs of rejection.

Animals↗
PubMed1991

The effect of antilymphocyte serum, fractionated donor bone marrow, and cyclosporine on renal allograft survival in mongrel dogs.

The effect of combined treatment with antilymphocyte serum, fractionated donor bone marrow, and a limited course of cyclosporine on renal allograft survival in mongrel dogs was examined. Recipients were treated with ALS from day -5 to day +7, relative to transplantation on day 0 with an MLR-mismatched donor. Fractionated donor bone marrow cells (BMFr3) obtained by density gradient separation were infused 3-7 days after ALS treatment. CsA treatments were begun either 3-7 days after ALS plus BMFr3 infusion or 3-7 days after treatments with ALS alone. Extended allograft survival was achieved at all CsA doses in BMFr3-infused, ALS-treated recipients. Allografts were sustained throughout the CsA treatment period without rejection in the majority of recipients (6 of 8) receiving ALS plus BMFr3 and CsA at 20 Mg/kg/day for 60 days. By contrast, few grafts were sustained through 30 days of treatment with CsA at 3.2 (1 of 12) or 10 mg/kg/day (2 of 9) in ALS plus BMFr3-treated recipients. Cyclosporine treatment was ineffective at all doses in augmenting allograft prolongation in ALS-treated recipients that did not receive BMFr3. Nearly all (6 of 7) long-term survivors (greater than 180 days) were BMFr3-treated. Peripheral blood lymphocytes or bone marrow cells of these long-term survivors proliferated normally in response to Con A and PWM, and were MLR responsive to third-party cells but did not have reduced MLR responsiveness to donor alloantigen in all cases. These long-term survivors promptly rejected third-party renal allografts without adverse effects on the original transplant's function. These results show that long-term renal allograft survival with specific unresponsiveness to the donor can result from the combined treatment with ALS plus donor BMFr3 and a limited course of CsA.

Animals↗
PubMed1991

Prevention of graft-versus-host disease following small bowel transplantation with polyclonal and monoclonal antilymphocyte serum. The effect of timing and route of administration.

Graft-versus-host disease is a potential problem following small bowel transplantation. We have previously shown that a two-day intraperitoneal course of polyclonal antilymphocyte serum completely prevents GVHD without impairing allograft function in a unidirectional rat small bowel transplant model. In the present study we sought to determine the optimum route and timing of ALS administration and whether donor pretreatment with the anti-T cell receptor monoclonal antibody R73 would be similarly effective in preventing GVHD. Both intravenous and intraperitoneal injection of ALS effectively prevent GVHD in this model. ALS must be given to donors at least 48 hr prior to graft procurement for maximum effectiveness. Prevention of GVHD correlates with lymphocyte depletion in mesenteric lymph nodes, as opposed to peripheral blood or small bowel lamina propria. Donor pretreatment with the monoclonal antibody R73 significantly delays the onset of GVHD in this small bowel transplant model but appears less effective than polyclonal ALS.

Animals↗
PubMed1991

Serological survey for Lyme disease in sika deer (Cervus nippon yesoensis) by enzyme-linked immunosorbent assay (ELISA).

Seventy-six wild sika deer (Cervus nippon yesoensis) from areas endemic for Borrelia burgdorferi during 1988 to 1989 had the IgG antibody to the bacteria in enzyme-linked immunosorbent assay. The percentage of seropositive deer was 25.0% to strain HO14 and 22.4% to strain HP3, respectively. Specific IgG antibody titers were high in summer but low in winter. In summer, seropositive deer were 75.0%. Similar results were obtained in serum specimens obtained monthly from 4 farmed deer. It was suggested that the sika deer could be one of the wild reservoirs for B. burgdorferi in Hokkaido, Japan. The transmission risk of B. burgdorferi is considered to be greatest during late spring to early summer.

Animals↗
PubMed1991

Changes in carboxylesterase isoenzymes of rat liver microsomes during hepatocarcinogenesis.

Among the three major carboxylesterase isoenzymes, RH1, RL1 and RL2, present in microsomes from normal rat liver, RL2 shows hydrolyzing activity towards 12-O-tetradecanoylphorbol-13-acetate and 1-oleoy1-2-acetyl-rac-glycerol, both activators of protein kinase C. Since protein kinase C has been suggested to be involved in carcinogenesis and cell proliferation, alterations in hepatic microsomal carboxylesterase isoenzymes including RL2 were studied during hepatocarcinogenesis induced by the Solt-Farber model. Alteration of RL2 was determined by measuring acetanilide-hydrolyzing activity, by quantifying the protein amount using the single radial immunodiffusion method, and by activity staining following electrophoresis of liver microsomes. The isoenzyme composition of hepatic microsomal carboxylesterase was changed after partial hepatectomy, and marked decreases in RL2 activity and protein content were observed at 4 weeks, at the time of preneoplastic foci induction. Partial hepatectomy alone also resulted in decreased RL2 activity. These findings suggest that RL2 may be involved in regulation of protein kinase C activity by metabolizing its activators at an early stage of hepatocarcinogenesis in rats.

Animals↗
PubMed1991

[Concentration of nitrosodimethylamine in commercial pelleted experimental animal diets].

To know the conditions of contamination by the chemicals in the experimental animal diets, the contents of nitrosodimethylamine (NDMA) were analyzed in the diets for mice and rats. The raw materials of the diets were also analyzed. In addition, NDMA levels were determined in the diets which were stored long or heated in the autoclaves. The averages of NDMA in these diets were less than 10 ppb. In the raw materials, alfalfa contained a higher levels of NDMA. There was no clear tendency of increase or decrease in NDMA levels, when the diets were stored for six months at room temperature (23-25 degrees C) or at low temperature (7-10 degrees C). Heating the diets at 121 degrees C, no remarkable changes were observed in NDMA levels. It seems that little adverse influences on the conduct of the animal experiments would be anticipated by the NDMA in the commercial diets.

Animal Feed↗
PubMed1991

[Changes in the blood cell counts with aging].

We analyzed the blood cell counts and serum levels of total protein (TP), total cholesterol (TC) and triglyceride (TG) of 2,231 healthy subjects (1,295 men and 936 women) between age 20 and 99 years in order to clarify the following two subjects. (1) In the approximately 10 years since the report of Shirakura et al in 1978, eating habits have improved and the average life expectancy has extended in Japan. Is there any effect of such betterment on blood cell counts of the aged? (2) It has been pointed out that quality of everyday life, such as staying at home but not in an old-age home, working, traveling, and so forth, had an influence on the blood cell counts of aged. Is there any difference between the blood cell counts of people under 60 years and those of people older than 60 years who have a good quality of life as mentioned above? The hemoglobin concentration, red blood cell count, and hematocrit value began to decrease in men in their sixth decade and in women in their seventh decade and the change was more prominent with advancing age, especially in men. The white blood cell count and platelet count tended to decrease with advancing age. The serum levels of TP, TC, and TG also declined with age in those over 60 years of age. These results confirmed that the hemoglobin concentration, red blood cell count, and hematocrit value decrease in the elderly subjects as they grow older and it may be considered that reduced ingestion of protein is one of the causes of the phenomenon.

Adult↗
PubMed1991

[Laboratory and clinical evaluations of flomoxef sodium in neonates].

Flomoxef sodium (FMOX) was evaluated experimentally and clinically in neonates. 1. Serum concentrations and urinary excretions of the drug were examined after a bolus intravenous injection at 20 mg/kg to 22 neonates 1-30 days after birth (durations of pregnancy 31-43 weeks, weights at birth 1,650-4,040 g) and 5 infants 50-95 days after birth (durations of pregnancy 33-40 weeks, weights at birth 1,720-3,308 g). Serum concentrations were 10.8-67.6 micrograms/ml (mean 32.7 +/- 2.8 micrograms/ml) and 25.1-52.0 micrograms/ml (mean 38.9 +/- 4.3 micrograms/ml) in the neonates and the infants, respectively, at their peaks (0.5 hour value), decreased thereafter with half-lives of 0.96-5.59 hours (mean 2.20 +/- 0.26 hours value), and 0.97-1.54 hours (mean 1.22 +/- 0.12 hours value), respectively. Serum levels decreased to 0.2-17.1 micrograms/ml (mean 2.9 +/- 0.6 micrograms/ml) and N.D. -1.1 micrograms/ml (mean 0.4 +/- 0.2 micrograms/ml) after 8 hours, respectively. The urinary recovery rates of the drug in the first 8 hours after administration were 15.0-96.0% (mean 53.7 +/- 4.9%) and 29.9-73.3% (mean 62.4 +/- 9.4%) in the neonates and in the infants, respectively. 2. FMOX was administered to 78 neonates (durations of pregnancy 31-42 weeks, weights at birth 1,420-3,860 g) in whom bacterial infections were established or suspected, and clinical, bacteriological, and side effects were evaluated. In 47 neonates examined (1 with sepsis, 3 with acute upper respiratory infections, 18 with acute pneumonia, 1 with umbilical infection, 1 with impetigo, 4 with acute urinary tract infections, 1 with acute otitis externa, 1 with periproctal abscess, and 17 with intrauterine infections), the treatment was markedly effective in 41, and effective in 6, with an overall efficacy rate of 100%. The bacterilogical effects of the drug on 3 strains of Staphylococcus aureus, 1 strain of Streptococcus pneumoniae, 1 strain of Streptococcus agalactiae, 9 strains of Escherichia coli, and 2 strains of Haemophilus influenzae which were responsible for these infections were all rated as "eradicated". Moreover, the drug, administered with or without prophylactic intentions showed complete prophylactic effects in all 27 cases tested. No side effects were observed in any of the patients. Concerning abnormal clinical laboratory results, increases in GOT were noted in 2, eosinophilia in 1, and thrombocytosis in 1, but these abnormalities were invariably mild and the normalized in 1 patient without treatment. The results suggest that FMOX is useful and safe also in neonates.

Bacterial Infections↗
PubMed1991

[A comparison of sudden near maximal exercise test (dash method) and Bruce protocol for pediatric patients].

We examined 24 pediatric patients to evaluate the usefulness of sudden near maximal exercise test (dash method), where the subjects began to run at Bruce protocol of the last stage. 1) No considerable differences between two protocols were found in maximal oxygen consumption (V O2max), maximal heart rate (HRmax), maximal systolic blood pressure, and findings of electrocardiography. 2) The sudden maximal exercise test could be completed during a shorter period compared to Bruce protocol. 3) The sudden maximal exercise protocol reached 84% of HRmax and 47% of V O2max at one minute after the onset of the protocol, and produced 96% of HRmax and 89% of V O2max at two minutes after the onset. We considered that sudden maximal exercise protocol was useful to obtain a response similar to Bruce protocol at maximal exercise within a short period. We have to pay attention to the safety of the patients because their cardiopulmonary response to sudden maximal exercise protocol is dramatic.

Adolescent↗
PubMed1991

[Clinical evaluation of cefixime in pediatric respiratory tract infections].

Cefixime (CFIX) was evaluated clinically in pediatric respiratory tract infections, particularly those caused by Haemophilus influenzae: 1. The total number of children in this study treated with CFIX was 232, out of which 215 cases were evaluated for clinical efficacy and 224 cases were investigated for safety. A daily dosage of 3-6 mg/kg/day was given divided into 2 to 3 times daily for 3-15 days. 2. Causative organisms were identified in 146 cases, out of which 128 cases were found to be single microbial infections and 18 cases were mixed infections. In single microbial infections, clinical efficacy was 100% for those caused by H. influenzae/Haemophilus parainfluenzae, and was 95% for Streptococcus pyogenes with an overall efficacy of 96.9%. In mixed infections, the clinical efficacy was 100% for those caused by a combination of H. influenzae and Streptococcus pneumoniae, and the overall rate was 94.4%. An involvement of H. influenzae was observed in 108 cases with a clinical efficacy rate of 99.1%, and definite involvement of beta-lactamase secreting strains of H. influenzae was found in 32 cases with a clinical efficacy of 96.9%. 3. Bacteriological effect was studied for 164 strains identified in 146 cases, and eradication rates were 89.5% for H. influenzae, 100% for H. parainfluenzae and S. pyogenes, and 71.4% for S. pneumoniae. The overall eradication rate was 91.4%. Superinfection was observed in 21 cases. MICs against 78 strains of H. influenzae were in a range of less than or equal to 0.10 microgram/ml regardless of beta-lactamase production, and far superior to cefaclor and amoxicillin. MICs against S. pyogenes and S. pneumoniae were in ranges of less than or equal to 0.10 microgram/ml and 0.39 micrograms/ml, respectively. 4. Clinical efficacy was 93.0% in 215 cases (excellent: 136, good: 64, fairly good: 10, poor: 5). CFIX attained a high efficacy in the range of 89.4-95.7% in acute pharyngitis, acute tonsillitis, acute bronchitis and acute pneumonia. 5. Safety was monitored in 224 cases and there were only one case of loose stool and another of diarrhea as side effects. There were no abnormal findings in 31 cases of the laboratory test. In conclusion, it was confirmed that CFIX is excellent and safe in the treatment of the respiratory tract infections.

Age Factors↗
PubMed1990

Selective cross-activation/inhibition of second messenger systems and the reduction of age-related deficits in the muscarinic control of dopamine release from perifused rat striata.

Possible alterations in muscarinic cholinergic (mACh) signal transduction in senescence were studied in rat neostriata. Acetylcholine (ACh) activation of striatal muscarinic heteroreceptors by carbachol or oxotremorine enhances K(+)-evoked release of dopamine from perifused striata of 6- but not 24-month-old rats. Present experiments determined the effects of simultaneous activation or activation/inhibition of more than one second messenger on K(+)-evoked release of DA from perifused striatal slices from these age groups. Combinations of carbachol (500 microns), which stimulates inositol-1,4,5-bisphosphate (IP3) production and inhibits cyclic AMP production, with oxotremorine (500 microns), which inhibits cyclic AMP production, in the presence of 30 mM KCl (in a modified Krebs-Ringer medium) reduced the age-related reduction in mAChR enhancement of DA release (analyzed by HPLC coupled to electrochemical detection; 5 min fractions were collected on ice in perchloric acid; flow rate 120 microliters/min). Combinations of these agonists with the putative second messenger arachidonic acid (10 microM), also enhanced K(+)-evoked release of DA in the striatal tissue from the 24-month group. IP3 activation was lower in the striatal tissue from old animals than those from young under all conditions, but cross-activation/inhibition actually may have lowered the IP3 threshold necessary for enhanced DA release to occur. In a subsequent experiment, pre-loading striatal tissue from young animals with either carbachol or oxotremorine under basal release conditions reduced the responding when the basal release medium was switched to one containing 30 mM KCl and combinations of the agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1990

Cloning of self-major histocompatibility complex antigen-specific suppressor cells from adult bone marrow.

We examined if suppressor cell clones may be established from adult bone marrow that contains a population of cells capable of specifically downregulating the immune response directed toward self-major histocompatibility complex (MHC) antigens. Freshly prepared adult C3H (H-2k) marrow cells were cultured in medium containing interleukin 2 (IL-2), IL-3, or a mixture of IL-2 and IL-3. After 7-10 d, cells grown in IL-3-containing medium were screened for their capacity to suppress cytotoxic T lymphocyte (CTL) generation against self-MHC antigens in allogeneic mixed lymphocyte cultures. Cells capable of suppressing anti-C3H CTL generation were cloned by limiting dilution. Several suppressor clones were established that exhibited strong suppression of anti-H-2k, anti-H-2Kk/Ik, and anti-H-2Dk CTL generation, but failed to suppress anti-H-2d and anti-H-2b responses. When tested in a skin allograft model, intravenous injections of these bone marrow-derived anti-self suppressor cells (2.5 x 10(7) cells) together with IL-3 induced prolongation of C3H skin allografts in anti-mouse lymphocyte serum-treated B6AF1 mice. Injection of IL-3 alone had no effect on allograft survival. Moreover, these cells failed to prolong B10.AKM skin allografts on B6AF1 recipients. Northern blot analysis showed that these cells express full-length transcripts of the T cell receptor (TCR) gamma gene, but not those of TCR alpha, beta, or delta genes. However, no rearrangement of gamma gene was observed by Southern blot analysis. Flow cytometric analysis revealed that bone marrow-derived suppressor cells are strongly positive for Thy-1 antigen but negative for CD3, CD4 (L3T4), and CD8 (Lyt-2) surface markers, and express only class I MHC antigens. Suppressor cells derived from adult bone marrow may play an important role in extrathymic induction of self-tolerance.

Animals↗
PubMed1990

Purification and characterization of glutathione transferases with an activity toward nitroglycerin from human aorta and heart. Multiplicity of the human class Mu forms.

Although recent studies suggest involvement of glutathione transferase (GST) of blood vessels in vasodilation by nitroglycerin, GST forms in blood vessels remain to be studied. In this study, three GST forms (pI values 8.3, 6.6, and 4.8) were purified from human aorta and four (pI values 6.0, 5.6, 5.3, and 4.6) from the heart by affinity chromatography followed by chromatofocusing. The major form of both aorta (pI 4.8) and heart (pI 4.6) was identified as GST-pi, and the other five forms were immunologically related to GST-mu, suggesting that the five belong to the Mu class. Among nine human GST forms, including three in the Alpha class purified from the liver, GST-mu, aorta pI 8.3 form, and GST-I (a form of the Alpha class, corresponding to GST-epsilon (B1B1)) showed high activities toward nitroglycerin, 1.08, 0.85, and 0.78 units/mg protein, respectively. GST-pi did not exhibit the activity. The Km values of the aorta form (pI 8.3) for glutathione (GSH) and nitroglycerin were calculated as 0.12 and 1.1 mM, respectively. The Km values of GST-mu and GST-I for GSH were 0.29 and 0.09 mM, and those for nitroglycerin were 2.5 and 0.3 mM, respectively. The activity of the pI 8.3 form as well as GST-mu toward nitroglycerin was inhibited by bromosulfophthalein, which is known to inhibit the relaxation of rabbit aorta induced by nitroglycerin, at the lower concentration (IC50, 2 microM) than was GST-I (IC50, 32 microM). Two-dimensional gel electrophoresis and N-terminal amino acid sequence analysis revealed that five forms in the Mu class are homo- or heterodimers of five different subunits named M1 (pI 7.0/Mr 27,000), M2 (6.6/27,000), M3 (6.0/27,000), N1 (6.5/26,500), and N2 (5.9/26,500). The subunit structures of the five forms are as follows: pI 8.3 form, M1M2; 6.6 form, M2N1; 6.0 form, M3M3; 5.6 form, M3N2; and 5.3 form, N2N2. M3 and N2 seem to correspond to the subunits of GST-mu, and -4 (Board, P. G., Suzuki, T., and Shaw, D. C. (1988) Biochim. Biophys. Acta 953, 214-217), respectively. These subunits except N1 are different from each other at two or three positions in the first 20 residues of N-terminal amino acid sequence. These results indicate the presence of five different subunits in the human Mu class and also suggest that GST-M1M2 and -M2N1 found in the aorta are involved in the expression of the pharmacologic effect of nitroglycerin.

Amino Acid Sequence↗
PubMed1990

Specific inactivation of glutathione S-transferases in class Pi by SH-modifiers.

Treatment of Class Pi glutathione S-transferases (GST) such as rat GST P (7-7), human GST pi and mouse GST MII with 0.05-0.1 mM N-ethylmaleimide (NEM) in 0.1 M Tris-HCl (pH 7.8) resulted in almost complete inactivation of these forms, whereas no or less inactivation occurred for GSTs in Class Alpha and Mu under the same conditions. Inactivated GST P lost its S-hexyl-GSH-Sepharose column affinity. About 0.8 mol of [14C]NEM was found to be covalently bound to 1 mol of GST P subunit when 80% of the activity was lost. Similar treatment with N-dimethyl-amino-3,5-dinitrophenyl maleimide, a colored analogue of NEM, followed by trypsin digestion, HPLC and amino acid sequence analysis revealed that one cysteine residue at the 47th position from the N-terminal of the GST P subunit was preferentially modified. Subunits of GST P and GST pi are known to have 4 cysteine residues at the same corresponding positions. The present results suggest that the 47th cysteine residue may be located in the vicinity of the active site of Class Pi GSTs.

Animals↗