Usefulness of bone SPECT of the cervical spine : With special reference to separate visualization of the trachea and thyroid cartilage

We applied bone SPECT for the examination of the cervical spine. A three-head rotating gamma camera SPECT system was employed for this study. The SPECT image disclosed 42.7 % of abnormal accumulations in the skeleton not seen with planar imagings. SPECT could separately visualize the trachea and thyroid cartilage and also provided interpretation of abnormality in the anterior part of the vertebral body being difficult with planar imagings only. The trachea cartilage was seen in 55.4% and the thyroid cartilage was seen in 47.3% of patients with anterior neck density in planar imagings. SPECT clarified that marked cervical curvature and diffuse high uptake by the skeleton might cause high intensity of the anterior neck in planar imagings in the case of non-pathological change. We concluded that bone SPECT is a useful diagnostic tool in detecting occult lesion in the skeleton and to rule out extraskeletal accumulations in examination of the cervical spine.     

Functional analysis of PIK3CA gene mutations in human colorectal cancer

Mutations in the PIK3CA gene, which encodes the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), have been reported in human cancers, including colorectal cancer. Most of the mutations cluster at hotspots within the helical and kinase domains. Whereas H1047R, one of the hotspot mutants, is reported to have elevated lipid kinase activity, the functional consequences of other mutations have not been examined. In this study, we examined the effects of colon cancer-associated PIK3CA mutations on the lipid kinase activity in vitro, activation of the downstream targets Akt and p70S6K in vivo and NIH 3T3-transforming ability. Of eight mutations examined, all showed increased lipid kinase activity compared with wild-type p110alpha. All the mutants strongly activated Akt and p70S6K compared with wild-type p110alpha as determined by immunoblotting using phospho-specific antibodies. These mutants also induced morphologic changes, loss of contact inhibition, and anchorage-independent growth of NIH 3T3 cells. The hotspot mutations examined in this study, E542K, E545K, and H1047R, all had high enzymatic and transforming activities. These results show that almost all the colon cancer-associated PIK3CA mutations are functionally active so that they are likely to be involved in carcinogenesis.     

Intraperitoneal injection of D-galactosamine provides a potent cell proliferation stimulus for the detection of initiation activities of chemicals in rat liver

In an in vivo 5-week initiation assay model, chemical hepatectomy by hepato-toxicant administration was utilized as a cell proliferation stimulus as an alternative to the two-thirds partial hepatectomy. The study investigated the effect of an intraperitoneal (i.p.) injection of D-galactosamine (D-gal) for this purpose in a medium-term liver bioassay, with a further focus on cell proliferation kinetics and cytochrome P450 (CYP) expression. In experiment I, cell proliferation in rat liver after a single administration of D-gal (700 mg kg(-1), i.p.) was analysed by the bromodeoxyuridine (BrdU) labeling method, and CYP isozymes were quantified by immunoblotting. In experiment II, the induction of glutathione S-transferase placental form (GST-P) positive foci by 1,2-dimethylhydrazine (DMH) was evaluated in a modified in vivo 5-week initiation assay model. At 84 hours after single administration of d-gal (i.p.) the BrdU index was markedly elevated (27.5% +/- 9.5%). Although CYP 2E1 and 1A2 apoprotein contents decreased transiently to less than 20% of the control level, subsequently they recovered to 60% and 40% of the control level, respectively, at 84 hours. Induction of GST-P positive foci in the group given DMH at 84 hours after a single administration of d-gal was significantly greater than in the control group, correlating with the kinetics of cell proliferation. In conclusion, the sensitivity of the present initiation assay using D-gal i.p. is high, so that D-gal i.p. can be considered an effective cell proliferation stimulus.     

Direct activation of STAT5 by ETV6-LYN fusion protein promotes induction of myeloproliferative neoplasm with myelofibrosis

Myeloproliferative neoplasms (MPN), a group of haematopoietic stem cell (HSC) disorders, are often accompanied by myelofibrosis. We previously identified the fusion of the ETV6 gene to the LYN gene (ETV6-LYN) in idiopathic myelofibrosis with ins(12;8)(p13;q11q21). The introduction of ETV6-LYN into HSCs resulted in fatal MPN with massive myelofibrosis in mice, implicating the rearranged LYN kinase in the pathogenesis of MPN with myelofibrosis. However, the signalling molecules directly downstream from and activated by ETV6-LYN remain unknown. In this study, we demonstrated that the direct activation of STAT5 by ETV6-LYN is crucial for the development of MPN. ETV6-LYN was constitutively active as a kinase through autophosphorylation. ETV6-LYN, but not its kinase-dead mutant, supported cytokine-free proliferation of haematopoietic cells. STAT5 was activated in a JAK2-independent manner in ETV6-LYN-expressing cells. ETV6-LYN interacted with STAT5 and directly activated STAT5 both in vitro and in vivo. Of note, ETV6-LYN did not support the formation of colonies by Stat5-deficient HSCs under cytokine-free conditions and the capacity of ETV6-LYN to induce MPN with myelofibrosis was profoundly attenuated in a Stat5-null background. These findings define STAT5 as a direct target of ETV6-LYN and unveil the LYN-STAT5 axis as a novel pathway to augment proliferative signals in MPN and leukaemia.     

Giant skull base atypical meningioma presenting with rapidly progressive impaired consciousness caused by severe venous congestion: case report

A 43-year-old female presented with a giant skull base atypical meningioma manifesting as rapid progression of impaired consciousness. The meningioma was located in the ethmoid sinus, sphenoid sinus, nasal cavity, and left middle temporal fossa, and the intracranial portion of the tumor involved the left temporal region with massive surrounding brain edema in the left temporal lobe and basal ganglia. She underwent emergent fronto-temporo-parietal decompressive craniectomy, and the intracranial portion of the tumor was resected to control intracranial pressure. She recovered consciousness and neurological function dramatically, and subsequently underwent radical tumor resection via combined extended transbasal and left lateral transzygomatic infratemporal fossa approaches one month after the initial surgery. The extensive brain edema completely disappeared after tumor resection, and the patient fully recovered without neurological deficits except anosmia and small visual field defect. Rapid neurological deterioration and disturbance of consciousness caused by extensive peritumoral brain swelling are unusual in meningioma. In this case, the extemporaneous decompressive craniectomy was highly useful in the management of increased intracranial pressure.     

A case of synovial chondromatosis of the temporomandibular joint followed for 17 years

The patient was a 52-year-old woman who visited our hospital for the chief complaint of a strange sensation in the left temporomandibular joint region on February 22, 1992. On the first examination, crepitus was heard, but no disturbance of mouth opening was noted. On panoramic radiography, radiopaque bodies were present in the left temporomandibular joint region, diagnosed as synovial chondromatosis. Course observation without active treatment was selected. Calcified bodies were noted on the lateral side directly below the left temporomandibular articular tubercle on the first computed tomography image performed in December 1998. Reportedly, this lesion grows slowly, but the lesions started to enlarge at a specific time point during the 17-year follow-up in this patient, showing the necessity of long-term follow-up by imaging even though no quality-of-life reduction or subjective symptom is observed.