The architecture of variant surface glycoprotein gene expression sites in Trypanosoma brucei

Trypanosoma brucei evades the immune system by switching between Variant Surface Glycoprotein (VSG) genes. The active VSG gene is transcribed in one of approximately 20 telomeric expression sites (ESs). It has been postulated that ES polymorphism plays a role in host adaptation. To gain more insight into ES architecture, we have determined the complete sequence of Bacterial Artificial Chromosomes (BACs) containing DNA from three ESs and their flanking regions. There was variation in the order and number of ES-associated genes (ESAGs). ESAGs 6 and 7, encoding transferrin receptor subunits, are the only ESAGs with functional copies in every ES that has been sequenced until now. A BAC clone containing the VO2 ES sequences comprised approximately half of a 330 kb 'intermediate' chromosome. The extensive similarity between this intermediate chromosome and the left telomere of T. brucei 927 chromosome I, suggests that this previously uncharacterised intermediate size class of chromosomes could have arisen from breakage of megabase chromosomes. Unexpected conservation of sequences, including pseudogenes, indicates that the multiple ESs could have arisen through a relatively recent amplification of a single ES.     

Regional cerebral blood flow (rCBF) in patients with ruptured cerebral aneurysm: site of aneurysm and rCBF

To investigate the relationship between the site of ruptured cerebral aneurysm and rCBF, 92 measurements of rCBF were conducted in 57 patients with ruptured cerebral aneurysm. Excluded from this study were patients with multiple aneurysms, intracerebral hematoma, and/or hydrocephalus. Twenty-four patients had the anterior communicating aneurysm (A-com), 20 patients had the internal carotid aneurysm (ICA), and 13 patients had the middle cerebral aneurysm (MCA). All patients underwent unilateral fronto-temporal craniotomy for clipping of the aneurysm and their rCBF measurements, using the xenon-133 inhalation method, were performed in the first three weeks after surgery. In each rCBF measurement, the hemispheric mean value of initial slope index (meanISI) was calculated in both cerebral hemispheres, that is, in the cerebral hemispheres ipsilateral and contralateral to craniotomy. The authors defined the "symmetry index of the meanISI (%): symmetry index" as the ratio of the meanISI in the cerebral hemisphere ipsilateral to craniotomy compared to the meanISI in the cerebral hemisphere contralateral to craniotomy. There was no significant relationship between the site of aneurysm and the meanISI in both hemispheres, and this result suggests that the site of aneurysm makes no difference in the incidence of vasospasm. In the postoperative first week, the "symmetry index" was 91.2 +/- 7.4% in MCA, 95.3 +/- 4.1% in ICA, and 97.9 +/- 8.2% in A-com; that is, MCA had significant asymmetry of meanCBF compared with A-com (p less than 0.05). In the second and third postoperative weeks, there was no significant relationship between the site of aneurysm and the asymmetry of meanCBF.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of subacute cerebral infarction demonstrating hyperemia and crossed cerebellar diaschisis in I-123 IMP SPECT

SPECT with N-isopropyl-p-[I-123]iodoamphetamine were performed in a 81-year-old man with cerebral infarction. In the subacute phase, the radioactivity was increased in the infarct area where fogging effect and remarkable contrast enhancement was demonstrated in X-ray CT. The contralateral cerebellar hemisphere showed reduced activity due to crossed cerebellar diaschisis (CCD). In the chronic phase, the decrement of the activity in the infarct was observed. Increased activity in the subacute phase was thought to reflect the hyperemia in the infarct, while CCD suggested the decreased metabolic activity in the lesion. The coexistence of the hyperemia and the CCD indicates flow and metabolic uncoupling, which means "luxury perfusion". This case was also thought to demonstrate atypical findings of CCD in SPECT imaging.     

The effects of butorphanol on baroreflex control of heart rate in man

The effects of butorphanol injection on baroreflex control of heart rate were investigated using both pressor and depressor tests in eighteen adult patients. Baroreflex sensistivity was attenuated after butorphanol injection in the pressor test using phenylephrine, whereas it was unchanged in the depressor test using nitroglycerine. No resetting of the baroreflex occurred after butorphanol injection. After the administration of butorphanol, plasma epinephrine and norepinephrine levels increased. These results suggest that it is safe to use butorphanol clinically even when a reduction in blood pressure due to hypovolemia or unclamping of the major artery is expected and that it is disadvantageous to administer the drug when an increase in blood pressure due to cross-clamping of the major artery is predicted.(Wajima Z, Inoue T and Ogawa R: The effects of butorphanol on baroreflex control of heart rate in man. J Anesth 7: 411--418, 1993)     

Surgical and preoperative treatment of soft tissue sarcoma

Preoperative therapy effects, resected margin and local radicality were investigated in 40 cases of soft tissue sarcoma in which preoperative therapy (mainly radiation therapy) had been given. The results indicated that there was no effect upon prognosis due to postponement of surgery in order to perform preoperative treatment. In cases in which radiation therapy was used for preoperative treatment, even when a surgical margin resulted with in a tumor, no recurrence was found. However, histologically there was concern that some portion of the living tumor cell in marginal area of the tumor might have remained. Thus, at the present stage in cases having undergone initial treatment, radiation limited to the specific area of the resected margin causing non-curative margin should be given. If combined with preoperative radiation therapy, surgical intervention involving "wide margin" can be considered radical. On the other hand, cases having undergone surgery before and receiving preoperative therapy that show good response nevertheless show numerous recurrences. These recurrences, however, invariably occur outside of the irradiated area, and may be attributed to the fact that tumor cell dissemination from the earlier surgery was not within the radiation field. Hence, it was considered that the area for radiation in the case of a recurrence should extend well beyond the scar area.     

白血病患者血清甲状腺激素水平测定的研究

为了解白血病患者血清甲状腺激素水平的变化,采用放免分析方法测定６７例不同类型白血病患者血清甲状腺激素水平,结果表明急性非淋、慢粒急变及急淋患者,血清三碘甲状腺原氨酸（Ｔ３）水平较正常显著降低,Ｐ〈０．０５,四碘甲状腺原氨酸（Ｔ４）水平无明显变化;促甲状腺激素（ＴＳＨ）仅慢粒急变时较正常升高（Ｐ〈０．０５）,游离Ｔ４（ＦＴ４）急非淋及慢粒急亦患者较正常降低（Ｐ〈０．０５）,而反三碘甲状腺原氨酸（ｒＴ３）较正常升高（Ｐ〈０．０１）,急淋ＦＴ４及ｒＴ３较正常升高（Ｐ〉０．０５）。提示甲状腺激素水平的变化主要在急非淋及慢粒急变者,在急淋变化不突出。     

Retrovirus-mediated gene-transfer of tnf receptor for treatment of cancer

Tumor necrosis factor-alpha receptor cDNA (TNFR-1 or TNFR-2) was inserted into a retrovirus derived vector. Recombinant vector was transfected into packaging cell line. The transfectants producing high titer of virus containing TNFR-1 or TNFR-2 cDNA were obtained. Human stomach cancer cells that poorly expressed TNFR-1 or TNFR-2 were infected with this virus as an in vitro model experiment of gene therapy. The stomach cancer cells that were infected with recombinant virus expressed TNFR-1 or TNFR-2 and were effectively killed by recombinant TNF.     

Interaction of the new histamine H2-receptor antagonist pibutidine hydrochloride with canine cloned H2-receptor expressed cells

The effect of a new histamine H2-receptor antagonist, pibutidine hydrochloride ((Z)-3-amino-4-{4-{4-[(piperidinomethyl)pyrid-2-yl]oxy} but-2-enylamino}cyclobut-3-ene-1,2-dione monohydrochloride, CAS 126463-66-9, IT-066 displaced the binding of [3H]tiotidine to cells transfected with the wild-type H2-receptor in a concentration-dependent manner. Compared with the 50% inhibitory concentration values (IC50) among five H2-receptor antagonists tested, the value of IT-066 was lowest. The inhibitory effect of IT-066 was enhanced by preincubation of IT-066 with the cells, and preincubation for 60 min increased potency about 2-fold. Famotidine also has such effects. When H2-receptor transfected cells were treated with IT-066 for 30 min, the inhibitory effect of IT-066 on the [3H]tiotidine binding still remained even after the cells were extensively washed. Scatchard plot analysis supported the non-competitive and irreversible action of IT-066. When the canine mutated H2-receptor-expressed cells were used, which have substituted amino acid of 190Alanine (Ala; position: 190th amino acid) for 190Threonine (Thr) in the fifth transmembrane domain, IT-066 also inhibited [3H]tiotidine binding to the cells concentration-dependently. However, in the case of the 190Ala mutated cells, the inhibitory effect of IT-066 attenuated with a decrease in maximal response after washing of the cells. These results show that IT-066 could tightly bind H2-receptor in a time-dependent manner and suggest the possibility that the irreversible inhibition of IT-066 is important in the interaction with 190Thr in the fifth transmembrane domain of H2-receptor.     

Vertebral decancellation for severe scoliosis

STUDY DESIGN: The results of staged surgery including vertebral decancellation were reviewed retrospectively for 21 patients with severe scoliosis. OBJECTIVES: To evaluate the benefits and limitations of vertebral decancellation as new anterior surgical procedure. SUMMARY OF BACKGROUND DATA: The curvatures of severe scoliosis are often very rigid, and surgical correction using the anterior or posterior approach may not achieve the desired correction. Some studies reported neurologic complications might appear due to the aggressive approach or excessive correction force. METHODS: Twenty-one patients (average age, 17.0 years) with severe scoliosis, in whom Cobb angle was over 80 degrees (average angle, 107 degrees), underwent staged anterior and posterior spinal reconstruction. Vertebral decancellation was performed as anterior procedure, and until posterior instrumentation, halo traction was carried out. The transition of curvatures in coronal and sagittal planes was assessed in this series. RESULTS: The average correction rate of lateral curvature at the final follow-up was 46%. The average loss of correction was 2.5 degrees. Kyphosis, measured between T5 and T12, changed from 41 degrees to 36 degrees. Lordosis, measured between L1 and S1, changed from 56 degrees to 45 degrees. Transient neurologic deficit was seen in one case after vertebral decancellation. CONCLUSIONS: Staged surgery including vertebral decancellation is an effective surgical method for patients with severe scoliosis, where an inflexible rigid curve or the risk of occurrence of neurologic complications due to temporary correction may exist.     

Epidermal growth factor receptor tyrosine kinase inhibitor does not improve paclitaxel effect in an orthotopic mouse model of lung cancer.

PURPOSE: The purpose is to evaluate whether inhibition of epidermal growth factor receptor (EGFR) activation by PKI166, an EGFR-tyrosine kinase inhibitor, affects growth of human lung cancer implanted orthotopically into the lungs of nude mice. EXPERIMENTAL DESIGN: Lungs of mice were injected with NCI-H358 human bronchioloalveolar cancer cells. In three experiments, groups of mice (n = 10 per group) were randomized 7 days after tumor implantation to receive one of the following treatments: i.p. paclitaxel 100 or 200 microg (4 or 8 mg/kg) once per week, oral PKI166 100 or 200 mg/kg three times per week, paclitaxel plus PKI166, or i.p. saline and oral PKI166-vehicle (control) for 5 weeks. Mice were killed 6.5 to 8 weeks after tumor implantation. The experiments were repeated with PC14PE6 human lung adenocarcinoma cells to assess effect on survival. RESULTS: Immunohistochemical analyses revealed the expression and phosphorylation of EGFR in the growing tumors. Treatment with PKI166 alone or in combination with paclitaxel diminished activation of EGFR on tumor cells, yet maximal therapeutic effect was observed in mice treated with paclitaxel alone. Activated mitogen-activated protein kinase and basic fibroblast growth factor expression were similar in all treatment groups. Survival in mice treated with the combination of paclitaxel and PKI166 was shorter than in those treated with paclitaxel alone. CONCLUSIONS: Our results suggest that concurrent administration of EGFR-tyrosine kinase inhibitor and chemotherapy is equivalent and may indeed be inferior to chemotherapy alone, even if EGFR is functional and its phosphorylation effectively inhibited. Our data show that the interaction of EGFR-TKIs and chemotherapy is complex and suggest that other growth factors may activate the downstream signaling events.