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.     

Prune Belly Syndrome: Report of Twelve Autopsy Cases and Possible Pathogenesis

Abstract Twelve autopsy cases (9 males, 3 females) of the prune belly syndrome are presented. Principal anomalies of this syndrome are a prune-like abdominal feature and a giant bladder. Urethral atresia was observed in most but two cases. Imperforate anus and rectovesical fistula were observed in 8 and 7 cases respectively. Associated anomalies were those which may or may not be embryologically related to the principal anomalies.
As regards the pathogenesis, the authors propose that a primary defect may occur during any developmental stage of the somitic mesoderm, genital tubercle and urethra. In conclusion, the prune belly syndrome may be of spectrum anomalies depending on the stage specificity mainly in the abdominal wall and genito-urinary organs.     

EXPERIMENTAL STUDY ON HEMORRHAGE IN THE BRAIN STEM INDUCED BY AN INTRACRANIAL SPACE OCCUPYING LESION

Increased intracranial pressure was experimentally produced in dogs by inserting a rubber balloon epidurally in the left temporal region and then inflating the balloon with water. The animals were killed after a set interval and the hemorrhagic lesion in the brain stem examined in detail. 1. The hemorrhagic lesions in the brain stem could be microscopically classified into three types; arterial, venous and capillary. Massive hemorrhagic lesion was also observed in some animals. 2. Arterial hemorrhage was distributed mostly in the area supplied by the thalamo-perforating artery in the diencephalon and in the area supplied by the paramedian branches of the basilar artery in the lower brain stem. Venous hemorrhage was found mostly in the region of the terminal vein and basal vein in the diencephalon and in the region of the basilar vein in the lower brain stem. Capillary hemorrhage was extensive and the distribution corresponded approximately with that of venous hemorrhage but also in part with that of arterial lesions. 3. A relation was apparent between the hemorrhagic lesion in the brain stem and the amount of water instilled into the rubber balloon, which could be correlated to intracranial pressure. Capillary hemorrhage was observed in most cases in which over 3.5 ml of water was instilled. With instillation of 4.0 ml of water, all types of hemorrhage were observed profusely but venos hemorrhage predominated. With instillation of more than 4.5 ml of water, arterial hemorrhage was dominant. 4. The relation between the hemorrhagic lesions and the survival time after procedure was studied in the animals which had died naturally. Capillary hemorrhage was observed in almost all the animals irregardless of the survival time. Both arterial and venous hemorrhage were observed abundantly in animals which survived for over 10 hours. Arterial hemorrhage, in particular, was dominant in the cases which died within 12 hours and the venous type was dominant in the case surviving over 12 hours.     

Neurofibromatosis complicated with XXX syndrome and renovascular hypertension

A 25-year-old woman with neurofibromatosis was admitted to our hospital for evaluation of hypertension. When she was 6 years old, she was diagnosed as having neurofibromatosis and XXX syndrome because of multiple café-au-lait spots, neurofibromas of the skin and mental retardation. Chromosome analysis revealed that her karyotype was 46, XX/47, XXX. Renal arteriography disclosed aneurysmal change and stenosis of the right renal artery. After right-side nephrectomy and aneurysmectomy, the kidney was autotransplanted in the left iliac fossa. Surgical procedure resulted in marked amelioration of the hypertension without medical treatment. Thus, aortorenal bypass and renal autotransplantation have emerged as the preferred revascularization operations. This is the first report of a chromosomal linkage between neurofibromatosis which is thought to be an autosomal dominant disease and the XXX syndrome.     

POLYARTHRITIS ASSOCIATED WITH HEPATITIS C VIRUS INFECTION

Two cases of polyarthritis associated with hepatitis C infectionare reported. In Patient 1, stiffness and polyarthritis occurredduring the acute stage of hepatitis. The arthritic symptomslasted for 4 months. A transient polyarthritis recurred 4 yrlater. The persistent presence of anti-hepatitis C viral antibodieswas noted. Hepatitis C viral RNA (HCV RNA) was identified inthe serum using the polymerase chain reaction proving that thepatient was a carrier. In Patient 2, polyarthritis occurredassociated with chronic hepatitis C liver disease. Synovialiopsy showed infiltration of mononuclear cells HCV RNA was demonstratedin both serum and SF. These cases suggest an aetiologic associationbetween arthritis and hepatitis C antigenaemia. KEY WORDS: Polyarthritis, Hepatitis C virus carrier, Chronic antigenaemia     

Infection of TT virus in patients with idiopathic pulmonary fibrosis

The precipitating factors of idiopathic pulmonary fibrosis (IPF) have not been elucidated. Recently, a novel DNA virus named TTvirus (TTV) was discovered in a patient with post-transfusion hepatitis of unknown aetiology TTV is a circular, single-stranded DNA virus of 3.8 kB. To evaluate the relationship between TTV and IPF, the sera of 33 patients with IPF were tested for the presence of TTV DNA by semi-nested polymerase chain reaction. TTV DNA was detected in 12 (36.4%) IPF patients. The serum lactate dehydrogenase (LDH) level was significantly higher in the IPF patients withTTV than in those without TTV (802 +/- 121 vs. 530 +/- 49 IU l(-1), p < 0.05). Six (50%) of 12 patients in theTTV DNA-positive group died during the observation period, while only six (28.6%) of 21 patients in theTTV DNA-negative group died. The 3-year-survival rate was significantly lower in the TTV DNA-positive group than in theTTV DNA-negative group (58-3% vs. 95.2%, P <0-02). Replicative intermediate forms of TTV DNA were detected in the lung specimen from a TTV-infected IPF patient. TTV infection influences the disease activityand prognosis of IPF in some cases. Further studies are required to elucidate the clinical significance of TTV in IPF.     

奈非那韦耐性细胞株对其它抗艾滋病药、抗肿瘤药的交叉耐性及多药耐药表型分析

目的在体外进行细胞对抗艾滋病药产生耐性的相关因子研究.方法通过将成人T细胞白血病细胞系MT-4培养于含有奈非那韦浓度不断增加直至14μmol/L的培养液中培养30天以获得耐奈非那韦的亚系细胞株MT-4rN.用细胞增殖分析系统四唑嗡染色法测定存活细胞数并用流式细胞仪及荧光化合物罗丹明-123和P-糖蛋白阻遏物维拉帕米分析多药耐药蛋白P-gp的存在.结果发现MT-4rN细胞对新近报道的抗艾滋病药K-37产生出比母本细胞多20倍的耐性.对其它抗肿瘤药的交叉耐性也有不同程度的提高.并且,耐性细胞的荧光密度在维拉帕米存在下有些不同,意味着P-gp在MT-4rN中的表达略有增多.结论在用HIV-1蛋白酶抑制物奈非那韦作用后,MT-4细胞对其它抗艾滋病药及抗肿瘤药产生了交叉耐性并且多药耐药蛋白P-gp的表达有所增加.