Assessment of insulin resistance in acromegaly associated with diabetes mellitus before and after transsphenoidal adenomectomy.

With a euglycemic hyperinsulinemic clamp method, whole-body insulin resistance was assessed in 6 cases with acromegaly associated with diabetes mellitus before and after transsphenoidal adenomectomy. The glucose infusion rate (GIR) correlated well with the plasma IGF-I level but poorly with that of GH. Further improvement in insulin sensitivity occurred 3-4 months after operation without substantial changes in plasma levels of both GH and IGF-I or glycemic control. These results indicate that GH excess can induce insulin resistance in association with plasma IGF-I and also through undefined secondary effect.

Different ratios in 20 S proteasomes and regulatory subunit complexes in two isoforms of the 26 S proteasome purified from rabbit skeletal muscle.

A ubiquitin/ATP-dependent proteinase complex (26 S proteasome) was highly purified from rabbit skeletal muscle. The purified 26 S proteasome easily dissociated into a 20 S proteasome and a regulatory subunit complex on non-denaturing PAGE. By using cleavable and non-cleavable cross-linkers, it was revealed that the 26 S proteasome exists in two isoforms: one (D complex) consists of the 20 S proteasome and the regulatory subunit complex in the ratio of one to two, while the other (C complex) exists in an equal molar ratio. Molecular masses of the former and the latter isoforms were estimated to be 1,700 kDa and 1,400 kDa, respectively, by gel filtration, and 2,400 kDa and 1,400 kDa, respectively, by Ferguson plot analysis. Furthermore, both isoforms efficiently hydrolyzed Suc-Leu-Leu-Val-Tyr-MCA and ubiquitin-conjugated [125I]lysozyme. These results suggest that the D and C complexes are active proteinase complexes, most probably corresponding to the dumbbell-like and mushroom-like (or space capsule-like) molecules, respectively.

[Detection of papillomavirus common antigens in plantar epidermoid cysts].

A total of 23 cases of human papillomavirus-associated epidermoid cysts, including one presented here, have been reported in Japan. A review of the literature revealed that the appearance of eosinophilic intracellular substances and that of vacuolar substances in the horny layer of cysts characterize these cases. High detection of human papillomavirus, the pathological features in these cases, and the observation of our case from the onset in which verrucous lesions had preceded a cyst may favor the possibility that HPV would directly produce cysts in these cases.

[Surgical treatment of ventricular septal rupture following myocardial infarction in an aged patient with bronchial asthma].

Urgent surgery for ventricular septal rupture following myocardial infarction in a 75-year-old female with bronchial asthma was successfully performed. On Feb 28, 1988, she had chest pain, and was admitted 5 days later because of the appearance of heart murmur. Pansytolic murmur (Levine 4/VI) on 3 LSB and piping sound on both lung fields was heard, ECG showed acute anteroseptal infarction. Right heart Swan-Ganz catheterization revealed left to right shunt, and the diagnosis was ventricular septal rupture following acute anteroseptal infarction with bronchial asthma. The initial hemodynamic condition was not serious, but soon after the diagnosis was confirmed, IABP was inserted and operation was indicated because of the advanced age, high shunt ratio (70%) and complication of bronchial asthma. The operation was performed a day after septal rupture. The perforation in the ventricular septum of the apex was sutured with a xenopericardium patch by mattres sutures through a left ventricle approach, and the ventricular wall was closed with this patch together. The postoperative course was uneventful, and the patient was discharged on the 43rd day after the operation.

[Plasma and tissue concentration of tegafur by a new soft capsule type suppository in colorectal carcinoma].

Plasma, tissue, and Lymph-node concentrations of tegafur and 5-FU were examined in 19 patients with colonic and rectal carcinoma after administration of tegafur by a new soft capsule type suppository: Plasma levels of tegafur and 5-FU after administration by soft capsule were much higher than those seen using supp. type suppositories. Tissue levels of 5-FU were high in tumor tissue compared to levels found in adjacent normal tissue. Lymph node levels of 5-FU were higher than plasma levels. Lymph node levels of 5-FU in the first-group lymph nodes were higher than in the second-group. These results suggest the clinical usefulness of administration of tegafur by soft-capsule suppository.

Effect of sustained-release theophylline administration on pituitary-thyroid axis.

The effect of therapeutic doses of theophylline on the pituitary-thyroid axis was studied in four normal adults and in 15 asthmatic children on theophylline treatment. In the four normal adults, sustained-release theophylline was administered every 12 hr for 60 hr, and serial determinations of serum theophylline, thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3), thyrotropin (TSH), and cyclic AMP (cAMP) were done. In all four cases, serum T4 increased significantly (134% +/- 4% vs basal level) with significant correlation to plasma cAMP level (r = 0.67, p less than 0.05). Changes in T3 and rT3 showed a marked individuality; an increase in T3 occurred in a subject with severe side effects, while the increase in rT3 was observed in a subject with mild side effects. Of the 15 children on theophylline treatment, a higher T4 level was found in 12 and a lower T3 level in nine at 1 wk, but these values returned to the previous level after 4 wk. These results indicate that the therapeutic doses of theophylline significantly but transiently increased the serum T4 level. In most cases, T4 is metabolized to rT3, an inactive metabolite of T4, but in a few cases it is metabolized to T3, which might double the side effects of theophylline.

Banded structure in solitary trichoepithelioma.

Electron microscopical observations were made in a case of solitary trichoepithelioma. Enlarged ERs were found in the tumor cells, showing a peculiar structure with fine granules and an electron-dense banded structure, about 50 nm wide respectively, lying at intervals of 250 nm. In addition to this structure, dense ovoid bodies, about 500 to 600 nm in diameter, were also observed.

Casein kinase in cytosol of rat and mouse mammary epithelial cells isolated from histone kinase by MgCl2 treatment and influence of pregnancy and lactation on the enzyme activity.

Rat mammary glands contain cyclic AMP-independent casein kinase and cyclic AMP-dependent histone kinase. The former was easily isolated from cyclic AMP-dependent histone kinase by MgCl2 treatment. Mammary casein kinase was not activated by cyclic nucleotides, and Mg++ and ATP were required for activation. The specific activity of casein kinase in cytosol of rat mammary epithelial cells increased 2 to 3-fold during pregnancy and lactation. Cytosol of mouse mammary epithelial cells also contained cyclic AMP-independent casein kinase, and the activity of this enzyme was about three times that of the Golgi fraction.

Studies on aclacinomycin A resistance in mouse lymphoblastoma.

An aclacinomycin A-resistant subline of mouse lymphoblastoma L5178Y cells was isolated by successive treatment of tumor-bearing mice with the antibiotic. IC50 (50% growth inhibition) in culture was observed at a drug concentration of 0.22 micrograms/ml, which was ca. 11 times higher than IC50 for the parental cells. The resistant cell line exhibited cross resistance to mitomycin C, actinomycin D, macromomycin, auromomycin, vinblastine, cytochalasin B, and other anthracyclines: daunorubicin, adriamycin, 4'-O-tetrahydropyranyladriamycin, baumycins A1 and A2, aclacinomycins B and Y, MA144-S1, 1-deoxypyrromycin, cinerubin A, musettamcyin, and pyrromycin. The 1-deoxy group of anthracyclines showed higher degree of cross resistance than the 1-hydroxy group. No significant cross resistance was found with bleomycin A2, neothramycin and blasticidin S. The resistance to aclacinomycin A and cross resistance to adriamycin were also demonstrated by the method of uridine incorporation. The accumulation or retention studies with [3H]adriamycin revealed that the resistance may be due to decreased uptake and increased efflux of the antibiotic in the resistant cells.

Mechanism of adriamycin resistance in a subline of mouse lymphoblastoma L5178Y cells.

The biochemical mechanism of anthracycline resistance was studied with an adriamycin-resistant subline of mouse lymphoblastoma L5178Y cells. Both uridine and thymidine uptakes in the resistant cells were observed more resistant to adriamycin and daunorubicin than those in the parental cells. Aclacinomycin A exhibited the same degree of inhibition of nucleic acid syntheses in the sensitive cells and in the resistant cells. The resistance pattern observed by the inhibition of RNA and DNA syntheses seemed to parallel that by growth inhibition. No significant difference was demonstrated between the parental and resistant cells in the inhibition of RNA and DNA polymerase reactions with isolated nuclei. The uptake and retention of [3H]adriamycin was observed significantly less in the resistant cells than in the sensitive cells. The results suggested that the adriamycin resistance may be due to alteration of the cytoplasmic membrane and/or cytoplasm, resulting in decreased uptake and retention of the antibiotic in the resistant cells.

Mechanism of action of macromomycin: DNA strand scission, inhibition of DNA synthesis and mitosis.

The effects of macromomycin (MCR), a high molecular weight peptide antibiotic, on cell division, DNA synthesis and DNA fragmentation were examined in cultured mammalian tumor cells. When MCR was added to HeLa cell culture simultaneously with [3H]thymidine, inhibition of DNA synthesis was observed depending on the amount of the drug present, although the inhibition was partial even at a high concentration of the drug. Preincubation of cells with MCR for 2 hours before assay was required for the complete inhibition of DNA synthesis. Cell division of synchronized L5178Y cells, arrested at metaphase, was strongly inhibited by MCR, indicating that the inhibition of cell mitosis by the drug was not dependent on the inhibition of DNA synthesis. Strand scission of DNA in MCR-treated cells was observed by alkaline sucrose gradient centrifugation. The fragmentation of cellular DNA occurred at low concentration of the drug and within a very short incubation time (37 degrees C, 5 minutes). At high concentrations of the drug, however, the size of the fragmented DNA remained constant. DNA polymerase activity in isolated nuclei from HeLa and L5178Y cells was stimulated by MCR. These data suggest that MCR works directly on cell nuclei and strand scission of DNA is one of the more important actions of the drug.