Cyclic peptides

In order to investigate the role of the L-2-hydroxy-3-methylbutanoic acid residue at position 2 of AM-toxin I (cyclic tetradepsipeptide) on necrotic activity for apple leaves, two analogs, [L-lactic acid²] AM-toxin I and [L-2-hydroxy-4-methylpentanoic acid²] AM-toxin I, were synthesized by the conventional method for peptide synthesis. The toxic activity of the former analog was much weaker than that of the natural AM-toxin I and the latter analog. CD spectra of AM-toxin I and these analogs were correlated to those toxic activities, indicating that bulkiness of the side chain at position 2 is important for the maintenance of active conformation and the induction of necrotic activity.     

Skeletal muscle regeneration induced by chorio-allantoic grafting

To examine whether the expression pattern of fast-muscle type troponin-T (TnT) isoforms was fixed in cell lineage, breast muscle pieces (pectoralis major) from chick embryos and young and adult chickens were grafted on to chorio-allantoic membrane of 9-day-old chick embryos and cultured until the host embryos hatched out. Muscle fibre formation of the grafts was investigated by histological and immunohistochemical methods with anti-fast-muscle type and anti-slow-muscle type TnT sera, and the expression of fast-muscle type TnT in the grafts from chick embryos and young chickens was studied by SDS-polyacrylamide gel electrophoresis (SDS-PAGE), two-dimensional SDS-PAGE, and immunoblotting. In the chorio-allantoic grafting, the breast muscle initially degenerated forming pyknotic nuclei and hyaline cytoplasm. The surviving cells, which were supposed to be satellite cells, regenerated new muscle fibres of the same type as those of the grafted muscle in respect of TnT isoform expression. Therefore, we considered that the ability to express specific isoforms of TnT was fixed in the satellite cells, and that chorio-allantoic grafting was a useful technique for studying muscle differentiation. This revised version was published online in August 2006 with corrections to the Cover Date.     

Vascular invasion of O-1N, hamster squamous cell carcinoma with high potential of lymph node metastasis: Ultrastructural comparison between lymphatics and blood vessels

The ultrastructural modes of lymphatic and blood vessel invasions were studied comparatively In hamsters with squamous cell carcinoma (O-1N) that had a high potential for lymph node metastasis. The endothellal injury, which was caused by mechanical stretching with the growth of O-1N, was the lnltial and characteristic feature common to both vascular invasions. Tumor cell nests penetrating the lymphatic lumen through disrupted endothellal cells still maintained their volume and continuity to the underlying tumor cell nests. In contrast, pronounced microthrombotic end neutrophllic reactions occurred at the site of blood vessel penetration. Within the lymphatic lumen, large clusters of O-1N cells were kept longer In spite of lymphocytic and macrophagic reactions. In blood vessels, clusters of tumor cells that had passed through dense fibrin layers were reduced In size and further disintegrated into smaller pieces by neutrophils. In conclusion, lymphatic invasion is a mechanical process, and smooth and direct invasion of large tumor cell nests into lymphatic vessels Is responsible for causing more prompt and frequent lymph node metastasis in O-1N than a hematogenous type.     

Generalized cold urticaria: detection of heat-sensitive passive transfer substance active at moderate temperature

An 11–year-old girl presented with generalized weal formation of 8 months' duration which occurred when she was cooled at rest or after physical effort. The ice cube test was only slightly positive. Injection of the patient's serum into her arm skin and into the skin of two volunteers produced immediate weals. This passive transfer reaction occurred most strongly at skin temperatures around 30 °C but not at 40 °C. The weal producing substance was provisionally identified as an unusual immunoglobulin M(IgM) by gel filtration, immunoadsorption and physicochemical treatments.     

Cyclic peptides. XVIII. Syntheses of AM-toxin I analogs containing bulky L-amino acid residues instead of an L-alanine*

In order to investigate the influence of the alanine residue at position 1 of AM-toxin I (cyclic tetradepsipeptide) on necrotic activity for apple leaves, three analogs, [l -2-aminobutanoic acid¹] AM-toxin I, [l -leucine¹] AM-toxin I and [l -phenylalanine¹] AM-toxin I, were synthesized by the conventional method for peptide synthesis. Spectra of ¹H-n.m.r., u.v. and CD of the analogs were similar to those of natural AM-toxin I. The analogs showed appreciable biological activity including host-specificity, indicating that considerable variation in the size of side chain at position 1 is allowed for the induction of necrotic activity.     

Trigeminal Neuralgia in a Patient with Marfan Syndrome: Case Report

Marfan syndrome can demonstrate tortuous and elongated intracranial arteries. However, these arteries rarely cause neurovascular compression resulting in hemifacial spasm or trigeminal neuralgia. The authors report a 33-year-old woman who was diagnosed as Marfan syndrome, suffered from trigeminal neuralgia. Magnetic resonance (MR) angiography showed tortuous and elongated left vertebral artery (VA). The coronal section of three dimensional (3D) MR cisternography with contrast enhancement showed that the left trigeminal nerve was compressed from underneath by the tortuous and elongated left VA. After successful surgery of microvascular decompression, the patient’s symptom resolved and no recurrence was encountered. Neurosurgeons should not only be aware of hemifacial spasm but also of trigeminal neuralgia caused by elongated vessels in a patient with Marfan syndrome, although it is an extremely rare condition. In addition, offending vessel is not atherosclerotic in younger patients unlike usual cases of trigeminal neuralgia. Thus, microvascular decompression can be easier than usual cases. Care should be taken to prevent arterial dissection during transposition by using some technical tips.     

Nephrotoxicity of Intravenously Injected Cadmium-Metallothionein: Critical Concentration and Tolerance

Nephrotoxicity of Intravenously Injected Cadmium-Metallothionein:Critical Concentration and Tolerance. MAITANI, T., CUPPAGE,F. E. AND KLAASSEN, C. D. (1988). Fundam. Appl Toxicol. 10,98-108. The nephrotoxicity of Cd-metallothionein (Cd-MT) wasexamined after iv administration of various dosages to mice.The lowest dosage of Cd-MT that produced renal injury was 0.2mg Cd/kg. This dosage of Cd-MT resulted in 10 µ Cd/g inthe kidneys 24 hr after administration. A time-course experimentutilizing a higher (0.3 mg Cd/kg) nephrotoxic dose of Cd-MTdemonstrated that the renal Cd concentration at 4 and 12 hrwas much higher than the critical concentration, but thereafterdecreased to about 10 Mg Cd/g wet tissue by 24 hr. Thus, Cdin excess of 10 Mg/g appears to damage the kidney and then distributesto other tissues and/or is excreted into urine. When a totalof 0.3, 0.4, and 0.8 mg of Cd/kg as Cd-MT was administered individed dosages over 4 days, as much as 30 Mg Cd/g was detectedin the kidney but no renal injury was observed. Thus, the criticalconcentration for producing renal injury after acute administrationof Cd-MT is estimated to be approximately 10 Mg Cd/g wet weight.However, with repeated exposure to Cd-MT, this acute criticalconcentration can be exceeded without producing renal injury,as tolerance to the nephrotoxic effects of Cd-MT develops.     

Increased expression of histamine H1 receptor mRNA in allergic rhinitis

Background Histamine plays an important role in producing nasal symptoms via histamine H₁ receptor (H₁R) in allergic rhinitis. It is reported that the minimum histamine concentration that induces sneezing is lower in allergic patients than in normal control subjects. Previous studies by binding assay on H₁R gave divided results on whether the number of H₁Rs is increased in allergic rhinitis or not. Objective The objective of this study was to examine if H₁R mRNA expression is increased in patients with allergic rhinitis compared with normal healthy volunteers. Methods We extracted RNA from scrapings of inferior turbinate mucosa of 10 patients suft'ering from allergic rhinitis and 10 control subjects. As the H₁R gene lacks introns. we treated RNA pellets by DNase to distinguish RNA from contaminating genomic DNA. Since amplification of H₁R and β-actin mRNA remained in an exponential phase at 35 cycles. H₁R and β-actin mRNAs were amplified for 35 cycles by reverse transcHption-polymerase chain reaction (RT-PCR). The PCR products were hybridized with internal probes and band intensities were quantitated by a densitometer. Results The mean ± sd of H₁R/β-actin ratio was 0.88 ± 0.62 for the patients with allergic rhinitis and 0.29 ± 0.17 for the normal subjects; the difference was statistically significant (P<0.01). Conclusions These data suggest that expression of H₁R mRNA is increased in the nasal mucosa of the patients with allergic rhinitis.     

Effect of allergen immunotherapy on nasal responses in guinea-pigs with allergic rhinitis

Methods We have investigated the effects of allergen immunotherapy on the nasal responses in the guinea-pigs with allergic rhinitis. Thirty-three male Hartley guinea-pigs with allergic rhinitis were divided into three groups; those receiving intradermal injection of saline (Group 1) or 0.1% ovalbumin (Group 2) 6 days after the last intranasal sensitization, and those injected with 0.1% ovalbumin intradermally once daily for 6 consecutive days from the next day after the last intranasal sensitization (Group 3). Results The dye leakage and histamine content into the nasal lavage significantly decreased at 30min after antigen challenge in Group 3, compared with Group 1 or 2. We also observed the change of mast cell numbers in superficial nasal mucosa, lamina propria and injected dorsal skin. The number of mast cells in superficial nasal mucosa significantly decreased in Group 3 compared with Group 1 or 2, but not those in nasal lamina propria or dorsal skin. Conclusions These results suggest that the improvements of nasal responses such as dye leakage and histamine content may be caused by the decrease of mast cell numbers in the superficial mucosal layer after the specific immunotherapy. which may be developing tolerance and one of the mechanisms underlying the beneficial effect of immunotherapy.