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Biomedical subjects

M Hatanaka

Publications and source records attributed to M Hatanaka.

412 records · Page 23Linked to original sources
PubMedDate not supplied

Analysis of C5b-8 binding sites in the C9 molecule using monoclonal antibodies: participation of two separate epitopes of C9 in C5b-8 binding.

C5b-8 binding sites in C9 were examined using mAbs raised against C9. Among 16 mAbs, two, designated P40 and X197, blocked C9-mediated EAC1-8 lysis. C9 pretreated with the mAbs failed to bind to EAC1-8 at 4 degrees C. In addition, the mAbs became inaccessible to the C9 that had been incorporated into EAC1-8 at 4 degrees C. These findings suggest that C9 binding to EAC1-8, but not its membrane spanning or polymerization, is blocked by mAbs. By immunoblotting analysis using alpha-thrombin proteolytic fragments derived from C9 [a N-terminal fragment of mol. wt 25,000 (C9a) and a C-terminal one of mol. wt 37,000 (C9b)] and tryptic fragments of C9 (mol. wts 53,000 (C9a') and 20,000 (C9b')), the epitopes of P40 and X197 were mapped to the N-terminal and C-terminal regions of C9b, respectively. Both P40 and X197 bound to the C9 polymerized with Zn2+ in the fluid phase, whereas X197 but not P40 reacted with the membrane attack complex (MAC) formed on membranes. The results suggest that two distinct epitopes are involved in C9 binding to EAC1-8, and behave in a different manner for globular C9 bound to EAC1-8 at 4 degrees C, C9 assembled in MAC, or poly-C9 induced by Zn2+. These mAbs may be useful in clarifying the conformational states of C9 and in analyzing the molecular interaction between C9 and its inhibitors.

Amino Acid Sequence↗
PubMedDate not supplied

Ha-ras oncogenes are activated by somatic alterations in human urinary tract tumours.

DNA-mediated gene transfer (transfection) studies using NIH 3T3 cells as recipients have demonstrated the presence of transforming genes (oncogenes) in diverse human tumours. A large proportion of oncogenes so far detected by DNA transfection are related to the Ha-ras onc gene of Harvey (and BALB) murine sarcoma viruses (MSV), Ki-ras, the oncogene of Kirsten MSV, and a third member of the ras gene family, N-ras. Individual tumours of many different organs have been associated with the activation of members of the ras gene family. We now present the first systematic survey of human urinary tract tumours processed immediately after surgery, as well as normal tissues from the same patients, to detect the presence of such genes. We demonstrate activation of Ha-ras as an oncogene in around 10% of randomly selected urinary tract tumours as well as direct evidence that oncogene activation is the result of a somatic event which is selected for within the tumour cell population.

Cell Line↗
PubMedDate not supplied

Twelve-hour cardiopulmonary preservation using donor core cooling, leukocyte depletion, and liposomal superoxide dismutase.

Because leukocytes and oxygen radical species contribute to ischemic and reperfusion injury during organ preservation, we examined the effects of a long-acting liposomal superoxide dismutase (liposomal SOD) and mechanical filtration of leukocytes on cardiopulmonary graft function after 12 hours of static preservation. Bovine heart-lung blocks were harvested, core cooled to 15 degrees C, stored in 4 degrees C donor blood for 12 hours, and then orthotopically transplanted (control group, n = 6). In the leukocyte-depletion group (n = 6), a leukocyte filter was incorporated in the bypass circuits of the donor and recipient. In the SOD group (n = 6), liposomal SOD (5000 U/kg) was administered in the cardioplegic solution, in the prime of the bypass circuits of donor and recipient, and immediately before recipient heart-lung reperfusion. In the combination group (n = 6), both leukocyte depletion (LD) and liposomal SOD were used. Only four of six control animals survived more than 2 hours after weaning from bypass, whereas all LD, SOD, and LD + SOD animals survived to be studied at 6 hours. Pulmonary function was assessed at 6 hours by arterial oxygen tension on 100% inspired oxygen (PO2), pulmonary vascular resistance (PVR), and postmortem wet/dry lung weight ratios. Arterial pO2 values (mm Hg) were as follows: control, 102 +/- 51; LD, 437 +/- 60*; SOD, 278 +/- 83; and LD + SOD, 504 +/- 54* (*p less than 0.05 vs controls). PVR values (dynes . sec . cm5) were as follows: control, 1975 +/- 697; LD, 682 +/- 131*; SOD, 607 +/- 191*; and LD + SOD 367 +/- 87* (*p less than 0.05 vs controls).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Effect of prostacyclin analog on pulmonary edema in isolated heart-lung autoperfusion model.

Pulmonary edema and impaired gas exchange function are worrisome early complications of heart-lung transplantation. The present study was designed to determine the effect of a new prostacyclin analog, OP-41483, on these complications with the use of a heart-lung autoperfusion model. Twenty-four mongrel puppies (4 to 6 kg) were evenly divided into four groups according to the oxygen content of inspired air (group 1, 95%; group 2, 60%) and the use of an intravenous drip of OP-41483 (0.1 microgram/kg/min) (group 3, 95% + OP; group 4, 60% + OP). During the course of these experiments, systolic pressure and cardiac output were maintained constant at 100 mm Hg and 40 ml/kg/min, respectively. Pulmonary arterial pressure was almost constant in each group throughout the experiment. Arterial oxygen tension (Pao2) was significantly decreased in groups 1 (410 +/- 49 to 237 +/- 38 mm Hg, p less than 0.01) and 2 (368 +/- 44 to 243 +/- 26 mm Hg, p less than 0.01) over the 5-hour autoperfusion period but was maintained at a high level in groups 3 (488 +/- 70 to 447 +/- 39 mm Hg) and 4 (431 +/- 33 to 430 +/- 35 mm Hg). Pathologic findings (perivascular edema and capillary dilatation) were significant in group 1 but less marked in group 2. However, no abnormal pathologic changes were observed in groups 3 or 4. These data demonstrated that OP-41483 was effective in preventing functional and pathologic pulmonary disturbances at a dosage (0.1 microgram/kg/min) that is reported to induce no undesirable hemodynamic effect.

Animals↗