Synthesis of analogs of K-582A,an antibiotic heptapeptide

K-582 A, an antibiotic heptapeptide, has a sequence of H-l -Arg-l -Arg(OH)-d -Orn-l -Thr-d -Orn-l -Lys-d -Tyr-OH (Arg(OH), threo-γ-hydroxyarginine). In order to investigate the relationship between structure and antimicrobial activity, four shortened analogs, des-l -Arg¹,l -Arg(OH)²-K582 A (pentapeptide), des-l -Arg(OH)²-K-582 A (hexapeptide) and their N-acetyl derivatives, were synthesized by the conventional method. None of them, however, showed any antimicrobial activity. Three more analogs, [l -Lys²]K-582 A, [l -Orn²]K-582 A and [l -Arg²]K-582 A, were synthesized. Among them, only [l -Arg²]K-582 A showed substantial activity against Candida krusei and Saccharomyces rouxii, indicating that the presence of a guanidyl side chain at position 2 is an essential factor for the induction of activity.     

Effects of a gastric mucosal protecting agent in rats with liver cirrhosis

Male Sprague-Dawley rats were fed a 0.1% ethionine-added choline-deficient diet for 8 weeks to induce liver cirrhosis. At the same time 100 mg/kg/day teprenone was administered orally in order to evaluate its effects on the liver and gastric mucosal blood flow. Blood flow increased not only in gastric mucosa but also in liver tissues in the teprenone group. Serum transaminase levels and histopathologic findings of the liver also improved. These findings suggest that teprenone alleviates hepatocellular injuries. This effect may be partly attributable to cytoprotective effects of the catenoid isoprenoid moiety of teprenone on liver cells.     

Two cases of insulin-dependent diabetes mellitus under insulin treatment with slow height velocity: Relationship of growth hormone-binding protein,metabolic control and growth

Inadequate blood sugar control in children with insulin-dependent diabetes mellitus (IDDM) sometimes results in low insulin-like growth factor-I (IGF-I) and sluggish height growth. High affinity growth hormone-binding protein (GHBP), which is identical to the extracellular domain of growth hormone (GH) receptor, is present in the human sera. We have determined GHBP activity in two cases of poorly controlled IDDM with low height velocity in relation to metabolic control in order to determine the mechanism of resistance to GH in this condition, as indicated by low levels of GH-dependent growth factor IGF-I in the face of high serum GH levels. GHBP activity was within the normal range in two cases of IDDM with slow height velocity, low IGF-I and high hemoglobin-A₁. In both cases, improved blood sugar control normalized IGF-I to result in accelerated height velocity without a major change in GHBP levels. These results may indicate either normal peripheral GH receptor or normal free portion of serum GH, and may suggest that the major defect in slow growth in poorly controlled diabetes is due to the post GH receptor.     

The relationship between serum transaminase activities and fatty liver in children with simple obesity

To determine hepatic diseases in obese children, biochemically and histologically, 11 obese patients with abnormal serum transaminase activities were subjected to this study. Fat accumulation in the liver was semiquantitatively graded, and histologically the 11 patients were classified into four groups; fatty liver, fatty hepatitis, fatty fibrosis and fatty cirrhosis. All patients had fat deposition in liver specimens, the grade of which did not significantly correlate with the degree of obesity. The grade of fat deposition in the liver specimens also did not significantly correlate with either serum transaminase activities or GOT/GPT ratio. Five patients were grouped into the fatty liver group, three into the fatty hepatitis group, and the remaining three patients into the fatty fibrosis group. However, no significant differences were found among the three histologically classified groups in terms of serum transaminase activities or GOT/GPT ratio. The usefulness of serum transaminase activities and GOT/GPT ratio was limited in predicting the severity of fat deposition or histological abnormality in pediatric obese patients.     

Differential Diagnosis of Respiratory Dyskinesia: A Prevalence Study Using Computer Analysis of Spirograph Data

A survey of respiratory dyskinesia for 248 inpatients receiving neuroleptic drugs was undertaken to explore the prevalence and subtype of respiratory dyskinesia using computer analysis of spirograph data monitored by both a Somniprobe nasal thermistor and a strain-gauge. By clinical examination, 23 patients showing irregular respiratory rate, tachypnea, or grunting were suspected to have respiratory dyskinesia. These 23 patients were then examined by nasal thermister for air flow, and strain gauge for thoracic movement. The coefficient of variation (CV) in distance from bottom to bottom of respiratory movements over 3 min was measured for each patient. For seven patients, their CVs were +2 SD greater than the mean CV found among 10 normal controls. The number of bursts of air flow (thermistor) was subtracted from the number of respiratory movements (strain gauge) as an estimate of desynchronization or obstruction. For three patients, this difference was +2 SD greater than the mean difference found among 10 normal controls. All three of these ‘desynchronized’ or ‘obstructive’ patients were among the seven who met ‘irregularity’ criteria as above. The prevalence of respiratory dyskinesia was 2·8 per cent (seven out of 248 subjects surveyed) and 13 per cent among those with TD populations. Respiratory dyskinesia was classified into two subtypes: the obstructive type with irregular respiratory movement and the irregular respiratory type. A computer analysis of spirograph data will be useful for the investigation of respiratory dyskinesia. © 1997 by John Wiley & Sons, Ltd.     

Formation and clinical significance of reddish markings on the liver surface: Activity of chronic liver disease

Background: The aim of this study was to clarify the clinical significance of reddish markings appearing on the surface of the liver. Methods: Subjects were patients with Hepatitis B virus‐related (n = 232) or Hepatitis C‐related (n = 246) chronic liver disease. Reddish lesions were obtained from this population using punch biopsy (n = 30) or wedge biopsy (n = 4), then studied histopathologically. In addition, the incidence and macroscopic forms of reddish markings in each laparoscopic stage for the 478 subjects were examined to determine when reddish markings appeared. Results: Reddish markings on the liver surface appeared only after the appearance of hepatic parenchymal destruction subjacent to the liver capsule, rather than with the appearance of piecemeal necrosis in the portal area. Moreover, following expansion of necrotic hepatic parenchyma subjacent to the liver capsule and distortion of hepatic lobular architecture in this lesion, net‐like or hemorrhagic fleck‐like reddish markings appeared. Therefore, this was recognized as changes at the liver capsule, such as capillary proliferation and dilatation, and blood flow changes in both the capsule and hepatic parenchymal lesions subjacent to the liver capsule. With regards to timing, reddish markings were most frequently observed in the transition to liver cirrhosis. After the appearance of reddish markings on the liver surface, chronic hepatitis rapidly progressed to liver cirrhosis. Conclusion: Reddish markings correspond to hepatic parenchymal destruction subjacent to the liver capsule, and not to piecemeal necrosis. Reddish markings appear in the transition to liver cirrhosis and might offer a useful marker of the progression to liver cirrhosis.     

Intra-His Bundle Block Corresponds with Interruption of the Branching Portion of the His Bundle

We compared His-bundle electrograms with pathological findings of the atrioventricular conduction system in four patients with complete atrioventricular intra-His block with narrow QRS complexes on ECG. Split His electrograms were recorded at the time of electrophysiological study. The patients died from noncardiac causes at 10 days, 1 year, 4 years, and 9 years, respectively, after the pacemaker implantation. Serial sections through the atrioventricular conduction system revealed strictly localized more than 50% reduction of conducting cells replaced by fibrosis at the branching portion of His bundle. The proximal portions of the bundle branches also exhibited decrease of the conducting cells showing a rough positive relation with the patient's age. Therefore, we considered that the H₁ spikes seen on His-bundle electrograms originated from the penetrating portion of His, which was virtually intact in our cases, and that the H₂ spikes originated from the right side of the distal branching portion of His.     

PLASMA CALCITONIN AND ACTH RESPONSES TO LYSINE VASOPRESSIN, CALCIUM AND PENTAGASTRIN IN A PATIENT WITH MEDULLARY THYROID CARCINOMA ASSOCIATED WITH CUSHING''S SYNDROME

In a case study of medullary thyroid carcinoma (MTC) associated with Cushing's syndrome, elevated levels of urinary 17-hydroxycorticosteroids, plasma ACTH, cortisol, calcitonin (CT) and somatostatin (GHRIH) were documented. Lysine vasopressin administration further increased the levels of plasma ACTH, cortisol and CT, whereas the administration of calcium and pentagastrin increased only the level of plasma CT. Immunoreactive ACTH, CT and GHRIH were highly concentrated in the tumour tissues. Basal plasma ACTH levels were more progressively increased than plasma CT during the postoperative course when the patient was treated with o,p'-DDD, since the tumour was not completely resected. These findings suggest that the secretion of ACTH and CT from MTC were regulated in a different manner.     

Studies of peptide antibiotics. XLIV. Syntheses and biological activities of gramicidin S analogs containing δ-hydroxy-l-norvaline or glycine

The antibiotic gramicidin S (GS) has the structure of cyclo (-l -Val¹-L-Orn²-l -Leu³-d -Phe⁴-l -Pro⁵-L-Val¹′-l -Orn²′-l -Leu³′-d -Phe⁴′-l -Pro⁵′-) and is basic in character. Five GS analogs including [Gly^1,1′]-GS and the neutral [l -Hnv^2,2′]-GS (Hnv represents δ-hydroxynorvaline) were synthesized by the solid-phase method to evaluate the role of l -Val^1,1′ and l -Orn^2,2′ residues in GS. The hybrid analogs ([Gly¹]-GS and [l -Hnv²]-GS) and [d -Tyr^4,4′]-GS showed high antibacterial activities, whereas [Gly^1,1′]-GS and [l -Hnv^2,2′]-GS possessed no activity. Inhibitory effects by these analogs for the adsorption of ¹⁴C-labeled GS on cells of bacteria sensitive to GS were determined. The structure-activity relationship of GS is discussed on the basis of the results on these GS analogs.     

Rectal absorption of insulin suppositories in rabbits

When insulin solutions (100 U kg^?1) at various pH values were placed in the rectum of rabbits, a large decrease in blood glucose concentration was observed except at the pH close to the iso-electric point of insulin. The effect of surface-active agents on the rectal absorption of insulin was examined by measuring the blood glucose concentration after the administration of 2 or 5 U kg^?1. Non-ionic ether type, anionic, cationic and amphoteric surfactants as well as bile acids increased the absorption. The optimal effect with suppositories was reached with the addition of 1% polyoxyethylene (9) lauryl alcohol ether. Insulin suppositories containing agents enhancing rectal absorption were compared with the insulin for intravenous, intramuscular and subcutaneous injection. The changes of blood glucose and plasma immuno-reactive insulin concentration after rectal administration of insulin were similar to those after intravenous injection.