A novel immunomodulator KRP-203 combined with cyclosporine prolonged graft survival and abrogated transplant vasculopathy in rat heart allografts.

To find more effective and less toxic immunosuppressive strategies in long-term treatment for organ transplantation patients, we examined the effects on rat heart allograft survival of a novel sphigosine-1-phosphate receptor agonist, KRP-203, combined with a subtherapeutic dose of cyclosporine (CsA). Rat heart transplantation was performed across a major histocompatibility complex-incompatible (DA to LEW) rat combination. KRP-203 alone showed little or no effect on heart allograft survival. In contrast, KRP-203 combined with a subtherapeutic dose of CsA led to prolonged allograft survival. Histologic analyses showed that the combination completely suppressed acute rejection, as characterized by allograft vasculopathy, mononuclear cell infiltration, and myocardial necrosis in the heart allografts. RT-PCR analysis showed that the allografts treated with CsA or KRP-203 alone showed no suppression of IL-10, IFN-gamma, and TNF-alpha mRNA expression, but when combined with a subtherapeutic dose of CsA it completely suppressed their mRNA expressions. Furthermore, the combination treatment reduced donor-specific antibody production. KRP-203 combined with a subtherapeutic dose of CsA synergistically prolonged rat heart allograft survival. The combination of CsA with KRP-203 may provide an option to prevent allograft rejection and reduce adverse effects.

Findings of pelvic musculature and efficacy of laparoscopic muscle stimulator in laparoscopy-assisted anorectal pull-through for high imperforate anus.

BACKGROUND: Laparoscopic findings of levator muscle and the efficacy of laparoscopic muscle stimulator (LMS) in infants with high imperforate anus have not been reported. METHODS: Twelve patients underwent laparoscopically assisted anorectoplasty for high imperforate anus. Following laparoscopic dissection of the distal rectum and division of the fistula, levator muscles in the pelvic floor were stimulated with a 5-mm-diameter LMS. Dilatation was done by inserting a guidewire and balloon catheter through the center of the levator muscle sling and muscle complex. Rectal pull-through and anastomosis between the rectum and anus were successfully completed. RESULTS: LMS showed good contraction of levator muscles and enhanced accurate midline placement of pull-through rectum. LMS was particularly useful in observing weak muscles in infants with rectovesical fistula. CONCLUSIONS: Laparoscopy and LMS offer excellent visualization of the pelvic musculature and precise tract of rectal pull-through. Fecal continence will be assessed by long-term follow-up.

Relationship between chemical structures and biological activities of triterpenoid saponins from soybean.

Saponins can be found in more than one hundred plant families and in some marine animals. However, chemical investigation of soybean (Glycine max L. Merrill) saponins has begun only as recently as the 1970s. Here we focus on the chemical structure, the content, and biological activity of soybean saponins in current studies. Especially, we focus on 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP) conjugated saponins and define the chemical structure of this as a natural precursor of group B and E saponins.

[Lymphocytic interstitial pneumonia associated with Sjögren's syndrome and mediastinal lymphadenopathy: diagnosis by open-lung biopsy].

A 56-year-old woman was admitted to the hospital because of dry coughing and shortness of breath on exertion. In addition, dry eyes and cornea guttata suggested Sjögren's syndrome. Chest radiography revealed linear, reticular shadows throughout the lung fields, and enlargement of hilar and mediastinal lymph nodes. A specimen was obtained by transbronchial lung biopsy but the findings were not condusive; open-lung biopsy was done. The histopathological findings suggested lymphocytic meterstitial pneumonia. Results of genetic analysis and of immuno-histochemical examination conformed that the proliferating lymphocytes were polyclonal. Corticosteroids and immunosuppressive drugs have been used to treat lymphocytic interstitial pneumonia, and they were effective in this case.

[Four important subjects of successful care at home for patients of terminally ill].

From April 1987 to May 1995, we have had care at home for 103 patients of terminally ill, and at this through our experience, we pointed out four important subjects for successful care at home. The first is prompt consultation at anytime when the patient or its family need. It is especially important when the patient's end time is near and previously we must fully instruct to patient's family how to consult and how to care. The second is effective palliative care. In these palliative care pain control with morphine is most important and we must master how to use morphine. The third is truth telling and informed consent. At treatment we have to communicate true information to patient. Home care must be started under patient's will. The fourth is organization of medical care, health care and welfare care. We have to make up network system of these office at first, and finally we have to make up community for supporting patients and these family.

[Pharmacokinetic, bacteriological, and clinical studies on SY5555 in children].

Pharmacokinetic, bacteriological and clinical studies on SY5555 were performed in children. The results were as follows: 1. A total of 15 patients considered to have bacterial infections were treated with SY5555. Each dose, 5 mg/kg, was orally administered 3 times daily, for 4-11 days. Clinical efficacies of SY5555 in 13 patients with bacterial infections (1 with pneumonia, 2 with bronchitis, each 1 with maxillary sinusitis, 2 with otitis media, 5 with pharyngitis, 1 each with gastroenteritis and pyelonephritis) were evaluated as excellent in 10 patients and as good in 3 patients with an efficacy rate of 100%. Two patients with viral infection and malignant lymphoma were not evaluated. Thirteen causative strains in 7 species were found in 10 patients. Streptococcus pneumoniae in 1/3, Haemophilus influenzae in 2/2, Streptococcus pyogenes 4/4, Salmonella spp. in 1/1, Escherichia coli in 1/1 were eradicated. Only one patient developed mild diarrhea as an adverse reaction. Another patient showed elevated GPT (glutamate pyruvate transaminase). The abnormality was mild and the patient recovered after the cessation of SY5555 administration without specific treatment. 2. MICs of SY5555 were examined against 33 clinical isolates. SY5555 has low MICs against Enterococcus faecalis and other Gram-positive cocci. 3. Pharmacokinetic studies Peak plasma concentrations of SY5555 was 1.15 micrograms/ml at a dose level of 4.9 mg/kg orally administered at fasting. Based on the above results and the broad spectrum of the anti-bacterial activities, SY5555 appears to be a promising antibiotics that is usable as a single agent for the primary therapy of respiratory tract infections, skin soft tissue infections and urinary tract infections in children.

[A case of repetitive monomorphic ventricular tachycardia].

We present a case treated with aprindine and metoprolol combined with a DDD type pacemaker for repetitive monomorphic ventricular tachycardia. A 50-year-old man was admitted because of palpitation and near syncope attack. Electrocardiogram showed repetitive monomorphic ventricular tachycardias (RBBB LAD type) and R-R interval of about 440 msec and I degree A-V block in sinus rhythm. Electrophysiologic study disclosed that overdrive pacing in HRA suppressed ventricular tachycardias. Left ventriculography revealed a dilated left ventricular and decreased contractility. Antiarrhythmic agents such as quinidine sulfate, procainamide, disopyramide, mexiletine, lidocaine and propranolol were not effective. But, the combination of propranolol and aprindine decreased the rate of the ventricular tachycardia. With aprindine 60 mg/day and metoprolol 60 mg/day combined with the atrioventricular sequential pacing at 85/min, ventricular tachycardia completely disappeared.

Purification and some properties of soybean saponin hydrolase from Aspergillus oryzae KO-2.

We had investigated the enzymatic hydrolysis of soybean saponins and selected soybean saponin hydrolase from Aspergillus oryzae KO-2. We attempted purification of this enzyme for further characterization. This enzyme was purified 1500-fold using ammonium sulfate fractionation and Sephadex G-200 gel filtrations. The enzyme was electrophoretically homogeneous and a glycoprotein by PAS staining. By gel filtration, the molecular weight of enzyme was 158,000 and SDS-PAGE showed the enzyme to have a tetrameric structure composed of heterogeneous subunits of 35,000 and 45,000. The enzyme activity was stable at temperatures below 40 degrees C and stable from pH 5.0 to 8.0. The optimum pH was pH 4.5 to 5.0 and the optimum temperature was 50 degrees C. The Km and Vmax for soyasaponin I were 0.48 mM and 9.8 mumol/hr mg protein, respectively. After hydrolysis with the enzyme, soyasapogenol B and alpha-L-rhamnopyranosyl (1----2)-beta-D-galactopyranosyl (1----2)-D-glucuronopyranoside were released from soyasaponin I.

[Serological diagnosis of pulmonary aspergillosis by ELISA].

Pulmonary aspergillosis usually develops on the basis of systemic immunosuppression and/or local impairments of respiratory system. Diagnosis of pulmonary aspergillosis has many difficulties. Chest X-ray findings of most cases are complicated with pre-existing changes due to the underlying diseases, and the detection rate of the pathogenic fungi from clinical specimens is unsatisfactorily low. Therefore, immunological or serological diagnosis is urgently required and precipitation-in-gel method has been widely applied. In this report, we compared clinical usefulness of the determination of anti-aspergillus antibodies by ELISA with that of precipitation-in-gel method. ELISA was carried out according to the method previously reported by us (Yamamoto S. et al.: Kekkaku 62: 549, 1987). About two-thirds of 45 healthy adults (control) did not show any detectable IgG anti-aspergillus antibody and mean of IgG anti-aspergillus antibody titer of the control group was 28.97. Patients, who had shown positive culture of fungus or was clinically diagnosed or strongly suspected as pulmonary aspergillosis, showed significantly high anti-aspergillus IgG antibody titer in comparison with the control group. Further, patients who were positive in precipitation-in-gel tests showed significantly higher IgG antibody titers than those who were negative in that test. IgG antibody titer determined by ELISA corresponded with clinical diagnosis much more exactly than the results of precipitation-in-gel test. Further, the results obtained by ELISA were objective and quantitative in comparison with the latter test. We concluded that ELISA was much superior to precipitation-in-gel test and that ELISA IgG antibody titers 2500 or more were confirmative and those between 570 and 2500 were strongly suggestive for the diagnosis of aspergillosis. IgM anti-aspergillus antibody titers were not different among healthy control group and patient groups, and could not be used for the diagnosis.