Association of epidermal growth factor receptor mutations in lung cancer with chemosensitivity to gefitinib in isolated cancer cells from Japanese patients

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are reported to be associated with clinical responsiveness of lung cancer to gefitinib, an EGFR tyrosine kinase inhibitor. To elucidate the association between somatic mutations and the pharmacological actions of gefitinib, the chemosensitivity of isolated cancer cells from the lungs of Japanese patients to gefitinib was examined by the collagen gel-droplet embedded culture drug sensitivity test in vitro. In 30 specimens isolated from non-small-cell lung cancer patients, mutations were observed in eight tumour specimens (27%) and chemosensitivity to gefitinib was observed in seven specimens (23%). However, somatic mutations were not predominantly associated with chemosensitivity to gefitinib in vitro. Both mutation and chemosensitivity frequencies in this study were higher than those reported in studies from the United States, indicating a possible ethnic difference. Moreover, both frequencies were much higher in females than in males. Since a gender difference in chemosensitivity to gefitinib was observed in isolated cancer cells in vitro, this suggests that gefitinib works in part through the suppression of EGFR signalling, but that other factors, including sex-related factors, may participate in gefitinib action.     

Efficacy of a direct puncture approach for anterior circulation aneurysms using a newly developed guiding catheter - especially for geriatric patients

BACKGROUND: Endovascular surgery is being increasingly used as an alternative to craniotomy clipping surgery, especially for aged patients and complicated cases. However, tortuous atherosclerotic arteries sometimes interfere with advancement of catheters so that direct puncture may be necessary. Short guiding catheters for use with this approach have been newly developed, as discussed in this article. METHODS: One hundred twenty three anterior circulation aneurysms in 121 patients were consecutively treated by endovascular coil embolization, of which 42 (34%) were older than 70 years. RESULTS: With 21 aneurysms, coil embolization via the transfemoral approach failed, but all could be successfully treated with the direct puncture approach with minor complications such as 1 transient ischemic attack and 1 nonsymptomatic minor leakage. In the aged patients, the direct puncture approach with short guiding catheter resulted in complete obliteration of aneurysms in 20 (71%) of 28 with follow-up angiography. CONCLUSION: Direct puncture using newly developed short guiding catheters is an alternative to femoral approaches for patients with anterior circulation aneurysm with tortuous arteries and obvious atherosclerotic change at bifurcations of the common carotid artery.     

Distinct effects of z-335, a new thromboxane A2 receptor antagonist, on rabbit platelets and aortic smooth muscle

The effect of a novel thromboxane A2 receptor (TP) antagonist, (+/-)-sodium[2-(4-chlorophenylsulfonylaminomethyl)- indan-5-yl]acetate monohydrate (Z-335), on the U46619-induced responses was compared between rabbit platelets and aorta. Z-335 inhibited platelet shape change induced by U46619 with higher efficacy than SQ29548, a common TP antagonist. The U46619-induced platelet aggregation was inhibited by Z-335 in a noncompetitive manner, while it was competitively inhibited by SQ29548. Z-335 inhibited U46619-induced vasoconstriction of rabbit aorta with higher efficacy than SQ29548. The pA2 value of Z-335 in aortic vasoconstriction was significantly higher than in platelet shape change. The competitive binding study showed the higher pKi value of Z-335 against [3H]-SQ29548 binding in rabbit aortic smooth muscle cells than in platelets. These data suggest that Z-335 has useful characteristics of TP antagonism.     

Neurokinin-1 receptors in the cerebrovascular vasoactive intestinal polypeptide-containing nerves in the rat

Recently, the functions of several putative neurotransmitters such as catecholmines, acetylcholine (ACh) and neuropeptides have been elucidated in the cerebrovasculature. The interaction of such neurotransmitters and their receptors, however, has not been sufficiently clarified. The purpose of this study is to explore the relation of recently demonstrated neurokinin-1 (NK-1) receptor-containing cerebrovascular nerve fibers with the cerebrovascular vasodilatory nerves by means of the sequential-staining immunohistochemical method. Numerous sites of NK-1 receptor immunoreactivities were noted along the nerve fibers with vasoactive intestinal polypeptide (VIP) immunoreactivity in the pial arteries in all regions of the brain. They consisted of fine, delicate varicose fibers and thick bundles without varicosities. After sequential staining with VIP, NK-1 receptor immunoreactive material was demonstrated in the VIP-positive nerve fibers. The majority of fibers were positive for VIP alone (75%). The number of fibers positive for both NK-1 receptor and VIP was about one-third the number of fibers for VIP alone (22%). Fibers positive for NK-1 receptor alone comprised a small population (3%). This study demonstrated that NK-1 receptors are localized in axonal membrane of VIP-containing parasympathetic nerves. This suggests that the sensory nerves modulate the functions of parasympathetic nerves in peripheral nervous system, such as those on cerebral vessels.     

Prenatal stress and postnatal development of neonatal rats--sex-dependent effects on emotional behavior and learning ability of neonatal rats.

Maternal sound stress (800 Hz; 77 dB, every other minute for 15 min/day, from day 10 to 18 of gestation), combined with forced swimming stress (15 min/day), was found to cause potentiation of sound-induced loss of locomotor activity, referred to as emotional behavior, of male offspring, but not that of female offspring, at 4 weeks of age. Maternal stress also caused an increase in the total number of errors by male, but not female offspring in the water-maze test at 6 weeks of age. These effects of stress on emotional behavior and learning behavior were abolished when dams were pretreated with buspirone (30 min before the stress, from day 8 to 18 of gestation). Thus, prenatal stress might have sex-dependent effects on emotional behavior and learning ability of neonatal rats.     

Spontaneous spinal epidural hematoma during pregnancy: three case reports

We present three extremely rare cases of spontaneous spinal epidural hematoma occurring in pregnancy. The patients developed progressive paralysis of the upper and lower limbs and the diagnoses were confirmed by magnetic resonance imaging. Urgent decompression is required to prevent neurological sequelae. The pregnancy may either be continued or delivered depending on the gestational age and severity of the disorder. Pregnancy-induced structural changes of the vascular walls and hemodynamic changes may play a role in the pathogenesis of spontaneous spinal epidural hematoma.     

Inhibitory effect of drug-free hybrid liposomes on metastasis of human neuroblastoma

Purpose  

Hybrid liposomes composed of vesicular and micellar molecules have been used as drug-delivery systems. It has become clear that hybrid liposomes alone have an inhibitory effect against the growth of various tumor cells. The present study was designed to determine whether a drug-free hybrid liposome composed of dimyristoylphosphatidylcholine (DMPC) and polyoxyethylenealkyl ether (EO) [90 mol% DMPC/10% C₁₂(EO)₂₁ (HL21), 90 mol% DMPC/10% C₁₂(EO)₂₃ (HL23), or 90 mol% DMPC/10% C₁₂(EO)₂₅ (HL25)], inhibit the liver metastasis of human neuroblastoma cells and thus increases survival.     

EOSINOPHILIC PUSTULAR FOLLICULITIS

• 1) Pustulosis pulmaris et plantaris-like lesions occurring often concurrently were studied clinically and histologically with the following results.
  • (1) The incidence of P.P.-like lesions occurring concurrently with eosinophilic pustular folliculitis is high.
  • (2) It increases and decreases almost in parallel with cutaneous lesions in other regions.
  • (3) It can be differentiated clinically from pustulosis pulmaris et plantaris.
  • (4) Cutaneous lesions are often seen on the elbow and knee in P.P. while it is often found in the face and back in eosinophilic pustular folliculitis.
  • (5) Unlike P.P. and eczema, they have a histology specific to this disease.
  • (6) They have a similarity to histology of the hair-root sheath.
  On the basis of the findings above, we think P.P. -like lesions are partial symptoms of this disease.
• 2) Since the palm and sole have no hair follicles, we think it is better to call this disease Eosinophilic pustular dermatosis.