Survey of <Emphasis Type="Italic">Ephedra </Emphasis>resources in the Northern Areas of Pakistan and their genetic diversity

More than 400 species of medicinal plants grow in the Northern Areas of Pakistan, including Ephedra plants. To investigate the wild Ephedra plant resources in the area, we surveyed the medicinal plants and collected 71 specimens from 18 collecting sites to analyze their genetic variation. The DNA sequences of the internal transcribed spacers 1 and 2 (ITS 1 and 2) of nuclear ribosomal DNA and a noncoding sequence of chloroplast DNA (trn L/F) were analyzed. This DNA data analysis and external morphological features were used to confirm the species of the specimens, and it was found that E. intermedia was the major species in the area and that E. gerardiana and E. przewalskii were present sporadically. Although it inhabits a relatively small area in comparison with the northwestern Chinese provinces, the DNA sequence of E. intermedia in the Northern Areas of Pakistan was significantly more heterogeneous than the same species grown in those neighboring regions. Most of the E. intermedia specimens contained more than 0.7% ephedrine alkaloids, fulfilling the requirement of the Japanese Pharmacopoeia; thus, the Ephedra plants in the area are a genetic and medicinal resource of great importance.     

Distribution of serotypes of S. pneumoniae in upper respiratory tract infections

Sixty strains of S. pneumoniae isolated from the patients with upper respiratory tract infections were immunologically classified by use of Danish type/group specific antisera. The percentages of S. pneumoniae serologically defined were 23.3% for Group 23, 20.0% for Group 19, 13.3% for Group 6, 10.0% for Type 3, 3.3% for Type 4, 3.3% each for Type 9 and 18, and 1.6% for Type 14. It was confirmed that in case of acute otitis media Group 19 and Type 3 were characteristic showing 30.0% and 13.4%, while rhinosinusitis were highly related to Group 23 of S. pneumoniae. An additional analyses revealed that Type 3 of S. pneumoniae were mostly found in the patients over 50 years old, though the patients under 5 years old were related to Group 19.     

p53 Gene Mutations in Human Prostate Cancers in Japan: Different Mutation Spectra between Japan and Western Countries

The involvement of p53 mutations in prostate cancers in Japan was investigated. To evaluate any possible clinicopathological significance, p53 mutations in 40 samples from 36 Japanese prostate cancers of different stages (five cases of latent tumors, three of stage A cancers, 10 of stage B, five of stage C and 13 of stage D), including four lymph node metastases of stage D cases, were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and sequencing. Mutations were detected in five of 40 samples (12.5%); four were in primary cancers and the other in a lymph node metastasis from one of them. All mutation-positive cases were in stage D, and the mutation frequency in stage D cases was 31%. This result indicates that p53 mutations may play a role in the progression of a subgroup of prostate cancers in Japanese, as observed for Americans and Europeans. However, a difference was noted between Japanese and Americans in the p53 mutational spectrum (at CpG site), presumably arising from variation in the underlying etiotogic factors.     

Intraoperative blood loss during cervical laminoplasty correlates with the vertebral intraosseous pressure

The systemic arterial pressure has been used as a guide for determining the susceptibility to surgical bleeding during controlled hypotensive anaesthesia. Arterial hypotension is not, however, necessarily accompanied by venous or intraosseous hypotension. The main source of bleeding during posterior spinal surgery is the bone and is venous rather than arterial. The intraoperative blood loss, the intraosseous pressure (IOP) within the first thoracic vertebral body, and the systemic arterial pressure were measured in 27 patients during cervical laminoplasty for spondylotic myelopathy. The intraoperative blood loss correlated significantly with the vertebral IOP (p = 0.0073, r = 0.499), but not with systemic arterial pressure, age, or body-weight. The systemic arterial pressure did not correlate with the vertebral IOP. The mean value of the mean arterial pressure throughout the operation varied between 74 and 110 mmHg. The findings suggest that the vertebral IOP parallels surgical bleeding during posterior spinal surgery under normotensive anaesthesia and that patients with a low arterial pressure do not necessarily have a low IOP.     

Age differences in phosphodiesterase type-IV and its functional response to dopamine D1 receptor modulation in the living brain: a PET study in conscious monkeys

The present study demonstrated the age-related changes in the striatal dopamine D1 receptor binding and its related cAMP second-messenger system in the living brains of conscious young (6.4 +/- 1.8 years old) and aged (19.5 +/- 3.3 years old) monkeys (Macaca mulatta) using positron emission tomography (PET). For quantitative analysis of D1 receptors, [11C]SCH23390 was used and phosphodiesterase type-IV (PDE-IV) activity, as an index of cAMP system, was estimated by two scans with R- and S-[11C]rolipram. Significant age-related decreases in D1 receptor binding were observed in the striatum and frontal cortex. Analysis of uptake of R- and S-[11C]rolipram indicated age-related decreases in PDE-IV activity showing 22.0 and 25.2% decreases in the striatum and frontal cortex, respectively, while no significant changes were observed in the cerebellum. With systemic preadministration of the dopamine D1 receptor antagonist SCH23390 (0.2, 0.6, and 2 mg/kg), the PDE-IV activities in the striatum and frontal cortex were dose-dependently suppressed in both age groups. However, the degree of suppression by SCH23390 was more marked in young than in aged monkeys. These results demonstrate that the striatal cAMP second-messenger system activity as well as its functional response to dopamine D1 antagonist showed age-related impairment in the brain.     

Phase I study of biweekly paclitaxel and carboplatin administration in patients with advanced non-small cell lung cancer

A phase I study of a biweekly outpatient regimen composed of carboplatin (CBDCA) and paclitaxel (TXL) was conducted for advanced non-small cell lung cancer. TXL was given in combination with a fixed dose of CBDCA (AUC 3) every 2 weeks. The starting dose of TXL was 100 mg/m2, and the dose was escalated in increments of 20 mg/m2. Three to six patients were allocated to each level. Toxicities were evaluated in the first 4 courses to determine the maximum tolerated dose (MTD). TXL 160 mg/m2 dosages proved to be MTD, and the dose limiting toxicity (DLT) was hematotoxicity (neutropenia). The patients, however, recovered from neutropenia using G-CSF immediately, when G-CSF was used. Gastrointestinal toxicity was well-tolerated. A response was found in 9 out of 20 patients who received 4 courses or more (45%). These results suggest that the recommended dose would be CBDCA (AUC 3) + TXL 140 mg/m2. The biweekly regimen has a high level clinical activity and excellent tolerability, and is suitable for outpatients. We started a phase II study because of these results.     

Systemic overexpression of the alpha 1B-adrenergic receptor in mice: an animal model of epilepsy

PURPOSE: A lack of selective alpha1-adrenergic receptor (alpha1-ARs) agonists and antagonists has made it difficult to clarify the precise function of these receptors in the CNS. We recently generated transgenic mice that overexpress either wild-type or a constitutively active mutant alpha 1B-AR in tissues that normally express the receptor. Both wild-type and mutant mice showed an age-progressive neurodegeneration with locomotor impairment and probable stress-induced motor events, which can be partially reversed by alpha 1-AR antagonists. We hypothesized that the wild-type and mutant mice may exhibit spontaneous epileptogenicity as compared with normal (nontransgenic) mice. METHODS: Normal, wild-type, and mutant mice were studied. Twenty mice (1 year old) underwent prolonged video-EEG monitoring over a 4-week period. Raw EEG data were blindly analyzed by visual inspection for the presence of interictal and ictal epileptic activities. RESULTS: During the acute postoperative period (< or = 3 days), both wild-type (26.1 +/- 8.07 spikes/day) and mutant mice (116.87 +/- 55.13) exhibited more frequent interictal spikes than did normal mice (2.17 +/- 0.75; p value, <0.05), but all three groups showed EEG and clinical seizures. During the later monitoring periods (>3 days), wild-type and mutant mice showed more frequent interictal spikes (15.44 +/- 4.07; p < 0.01; and 6.05 +/- 2.46; p < 0.05, respectively) as compared with normal mice (0.41 +/- 0.41), but only mutant mice had spontaneous clinical seizures (means +/- SEM). CONCLUSIONS: The selective overexpression of the alpha 1B-AR is associated with increased in vivo spontaneous interictal epileptogenicity and EEG/behavioral seizures. These results suggest a possible role (direct or indirect) for the alpha 1B-ARs in the development and expression of epileptogenicity.     

Embolization of the right gastric artery before hepatic arterial infusion chemotherapy to prevent gastric mucosal lesions: approach through the hepatic artery versus the left gastric artery

OBJECTIVE: The purpose of our study was to evaluate whether the hepatic artery or the left gastric artery is the better route of approach for selective embolization of the right gastric artery before hepatic arterial infusion chemotherapy using a port-catheter system. SUBJECTS AND METHODS: Eighty-six patients (56 men, 30 women; mean age, 62.1 years) with unresectable advanced liver cancer underwent percutaneous implantation of a port-catheter system. In the 75 patients who had not undergone gastrectomy, right gastric artery embolization was performed before port-catheter system placement to prevent gastric mucosal lesions. In 43 patients, the approach for embolization was through a microcatheter inserted from the hepatic artery site, and in the remaining 32 patients, the approach was from the left gastric artery. The success rates of these two groups were compared. RESULTS: Embolization was successfully accomplished at the first attempt in 72.1% of the 43 patients in whom the microcatheter was inserted from the hepatic artery site. In contrast, in 93.8% of 32 patients, embolization was successfully performed through the left gastric artery. The success rate of embolization was significantly higher in the latter group (p = 0.0173, chi-square test). A second attempt in which the catheter was redirected to another approach, performed on the same day in a majority of patients, resulted in successful embolization in an additional eight patients, with a final success rate of 92.0%. CONCLUSION: Embolization of the right gastric artery using microcoils through a microcatheter advanced through the left gastric artery may be the preferred method for the preparation of repeated hepatic artery infusion.