Association of myopathy with large-scale mitochondrial dna duplications and deletions: Which is pathogenic?

We identified large-scale heteroplasmic mitochondrial DNA (mtDNA) rearrangements in a 50–year-old woman with an adult-onset progressive myopathy. The predominant mtDNA abnormality was a 21.2–kb duplicated molecule. In addition, a small population of the corresponding partially deleted 4.6–kb molecule was detected. Skeletal muscle histology revealed fibers that were negative for cytochrome c oxidase (COX) activity and had reduced mtDNA-encoded COX subunits. By single-fiber polymerase chain reaction analysis, COX-negative fibers contained a low number of wild-type or duplicated mtDNA molecules (ie, nondeleted). In situ hybridization demonstrated that the abnormal fibers contained increased amounts of mtDNA compared with normal fibers and that most of the genomes were deleted. We concluded that deleted mtDNA molecules were primarily responsible for the phenotype in this patient.     

An ultrastructural study on anterior cruciate ligament reconstruction using autogenous patellar tendon grafts in dogs

An ultrastructural study was undertaken concerning morphological changes within the autografted patellar tendon (PT) after being transplanted to the anterior cruciate ligament (ACL) in mongrel dogs. After 4 weeks, the arrangements of both large and small collagen fibrils in the PT graft became disordered, and the number of inflammatory cells increased. However, the same PT grafts revealed postsurgical signs of newly-produced collagen fibrils around activated fibroblasts at 12 to 24 weeks. At 52 weeks after the transplantation, small collagen fibrils increased in both number and density, showing a remarkable morphological similarity to the collagen fibrils of normal ACL. These data indicate that the characteristics of the PT graft eventually resemble those of a normal ACL. This paper was presented in part at the Combined Meeting of the Orthopedic Research Societies of the USA, Japan and Canada in Banff, Alberta, Canada, October, 1991.     

Benastatins A and B, new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. I. Taxonomy, production, isolation, physico-chemical properties and biological activities.

Benastatins have been isolated as part of a program designed to find microorganism-produced inhibitors of glutathione S-transferase from Streptomyces sp. MI384-DF12. They were purified by chromatography of reversed-phase silica gel, silica gel and Capcell Pak C18 (HPLC) followed by solvent extraction and then isolated as yellow powders. Benastatins A and B have the molecular formulae, C30H28O7 and C30H30O7, respectively. They were competitive with 3,4-dichloronitrobenzene as the substrate, and the inhibition constants (Ki) of benastatins A and B were 5.0 x 10(-6) and 3.7 x 10(-6), respectively.     

A case of multiple leiomyomatous lesions of the lung: An analysis of flowcytometry and hormone receptors

A 36 year old woman was admitted to our department because of a chest X-ray which showed multiple developing shadows. She underwent bilateral exploratory thoracotomies and a total 5 tumors were resected and pathologically diagnosed as benign metastasizing leiomyoma, the largest of which was positive for the progesterone receptor and negative for the estrogen receptor. A histogram of this tumor using a flow cytometer showed a diploid pattern and 4.6 percent of the S phase which was not more than that of a leiomyoma of the uterus from another patient. Two months later, she underwent a hysterectomy and bilateral salpingo-oophorectomy for treatment of the positive progesterone receptor in the pulmonary lesions. The resected uterine myoma and normal myometrium showed positive estrogen and progesterone receptors. For the subsequent 28 months she has been free of any further symptoms. Benign metastasizing leiomyoma of the uterus is a rare disease and very interesting because of its histological benignity and hormonal dependency. However, according to the literature, it is often confused in entity due to the fact that normal lung tissue also possesses hormone receptors. Considering our data on hormone receptors, it is rational to think that multiple leiomyomatous lesions in the lung should only be diagnosed as benign metastasizing leiomyomas when they possess positive estrogen and progesterone receptors.     

Ouabain as an amplifier of mineralocorticoid-induced hypertension.

Ouabain has recently been reported to be an endogenous Na, K-ATPase inhibitor. To evaluate whether it exerts hypertensive action itself or amplifies the hypertensive action of small doses of mineralocorticoids, 5 mg deoxycorticosterone acetate (DOCA), 1 mg ouabain, or a combination of both were injected into mononephrectomized rats weekly for 6 weeks, and changes in blood pressure were evaluated. The blood pressures of control, DOCA-treated, ouabain-treated, and the combination treatment group at the sixth week were 138 +/- 3 (SE), 160 +/- 6, 144 +/- 6, and 201 +/- 14 mmHg, respectively. The blood pressure of rats given DOCA or ouabain alone was not significantly different from that of controls. In contrast, the blood pressure of rats given the combination of DOCA and ouabain was significantly higher than that of control rats and those given DOCA or ouabain separately. Cardionephromegaly and histopathological changes found in rats given the combination of DOCA and ouabain were consistent with the effects of an elevation of blood pressure. Further evaluation revealed that the amplification effect of ouabain on the hypertensive action of DOCA was dose dependent, with the minimum dose that caused the amplification effect being 0.25 mg/week. These results indicate that ouabain, although devoid of hypertensive action itself, amplifies the hypertensive action of small doses of DOCA and can cause a hypertensive state similar to that induced by larger doses of DOCA. It is inferred that the amplification effect of ouabain on mineralocorticoids is important in the genesis of hypertension.     

A composite nasolabial flap for an entire ala reconstruction.

BACKGROUND: It is difficult to reconstruct an entire alar defect. We report a case of an entire alar reconstruction carried out in two stages with a composite nasolabial flap lined with retroauricular skin and supported with the attached conchal cartilage. OBJECTIVE: A composite nasolabial flap was applied for reconstruction of entire alar defect in this patient. METHODS: The lining skin for the flap was obtained from retroauricular region acceptable to the patient, and the conchal cartilage was used simultaneously for support and as the attachment for the lining skin. The flap was then replaced and secured. Half a year later, the flap was flipped and transferred to the alar defect as a second step. RESULTS: The final shape and texture were satisfactory. All procedures were performed under local anesthesia. CONCLUSION: Our design of composite flap has been successfully utilized to repair an entire alar defect with cosmetically and functionally good results, minimizing the donor area and the resulting operation scars. This composite nasolabial flap is thought to be the best choice of a flap for an entire alar defect reconstruction.     

INTRA- AND INTERINDIVIDUAL VARIATION IN THE PHARMACOKINETICS OF TACROLIMUS (FK506) IN KIDNEY TRANSPLANT RECIPIENTS—IMPORTANCE OF TROUGH LEVEL AS A PRACTICAL INDICATOR

Background: Tacrolimus (FK506) is currently used as the primary immunosuppressant in clinical kidney transplantation in some centers. The purpose of this study was to evaluate the pharmacokinetics of this drug and to see if trough level, which has been used widely in therapeutic drug monitoring, can be used as an appropriate substitute for other pharmacokinetic measurement tests. Methods: The blood concentration-time curve was studied in 10 kidney transplant recipients on 26 Occasions after oral dosage of 2 to 18 mg every 12 hours. Whole blood concentration was measured by two-step irnmunoabsorption assay. Methylprednisolone was used as a concomitant immuno-suppressive drug. Results: The blood concentration-time curves showed remarkable interindividual variation. lntraindividual variation was also found, but the degree of variation was slight compared with interindividual variation. On 17 occasions of measurement in one patient, the dose was significantly correlated with trough (r = 0.684). C_max (r = 0.838) and AUC_0–12 (r = 0.817). In nine patients on nine occasions, however, the dose was not significantly correlated with trough (r = 0.351), C_max (r = 0.270) or AUC_0–12 (r = 0.355). t_max ranged from one to four hours (mean + SD; 2.8 + 1.3) and fluctuated in both intra- and interindividual measurements. In spite of a wide variation in the blood concentration-time-curve patterns, a highly significant linear relationship between trough and C_max or AUC_0–12 was observed in both intraindividual (C_max, r = 0.876; AUC_0–12, r = 0.926) and interindividual (C_max, f = 0.943; AUC_0–12, r = 984) measurements. Concluslons: We conclude that trough level is a practical acceptable indicator of the blood levels of tacrolimus, and can be used to monitor blood concentration.