PubMed Health⌕ Search

Biomedical subjects

J Hamada

Publications and source records attributed to J Hamada.

At least 37 records · Page 2Linked to original sources
PubMed2000

Inhibition of cytoplasmic DNA synthesis may be an initial signal for the induction of sexual reproduction in Closterium ehrenbergii.

We investigated the effect that inhibitors of cytoplasmic DNA (cytDNA) and/or nuclear DNA (nDNA) synthesis have on the frequency of zygote formation in Closterium ehrenbergii and whether these inhibitors correlate with arrest of pyrenoid production and enlargement of pyrenoidal size accompanying pregametogenesis in the alga. CytDNA inhibitors, ethidium bromide (EB), acridine orange and novobiocin (NB), enhanced zygote formation in the presence of nitrate, and these chemicals correlated with both a decrease in pyrenoid production and an increase in pyrenoidal size. By contrast, a nDNA inhibitor, aphidicolin (APC), enhanced zygote formation in the presence and absence of nitrate, and correlated with only an increase in pyrenoidal size. Meanwhile, inhibitors of both nDNA and cytDNA synthesis, mitomycin C (MC), hydroxyurea (HU) and arabinosyl cytosine (Ara-C), enhanced zygote formation in the presence and/or absence of nitrate. In addition, MC and HU correlated with only an increase in pyrenoidal size and Ara-C only a decrease in pyrenoid production. This result seemed to indicate that MC and HU functioned as selective inhibitors of nDNA synthesis, and Ara-C as a selective inhibitor of cytDNA synthesis. It is suggested that differentiation into pregametes correlates with the inhibition of both nDNA and cytDNA synthesis, levels of which are probably low, the inhibition of cytDNA synthesis being the initial signal for pregametogenesis.

Journal Article↗
PubMed2000

Transcriptional slippage of p53 gene enhanced by cellular damage in rat liver: monitoring the slippage by a yeast functional assay.

The Long-Evans Cinnamon (LEC) rat is a mutant strain characterized by abnormal copper metabolism and a high incidence of hepatitis and hepatoma. Using a yeast-based assay which scores mutants in p53 gene transcripts as red colonies, we detected frequent mutations in the liver of LEC rats. The majority (50-60%) of these were frameshift mutations caused by the insertion of an extra adenine (A) in the regions containing six consecutive adenines. The rate of A insertion was calculated to be 6.9-9.0% of the total p53 cDNA. Insertions of an extra adenine were found almost exclusively in the mRNA (cDNA), especially in the (A)(6) tract located at the most 5'-side (exon 4) among the three (A)(6) tracts (exons 4, 7, and 8), but rarely in the corresponding sites of genomic DNA. Wild-type p53 cDNA was transcribed in vitro into mRNA with the use of SP6 RNA polymerase and tested by the yeast functional assay. Subsequent sequencing detected A insertions at an overall rate of 1.6% in exons 7 and 8 but none in exon 4. This indicates that the A insertion in the exon 4 (A)(6) tract was an in vivo phenomenon rather than an artifact in reverse transcription or polymerase chain reaction. The percentage of red colonies increased sharply to about 20% of the liver samples in the acute hepatitis stage, and returned to control level of those in the chronic hepatitis stage, and increased again slightly to those in the neoplastic stage. The percentage of red colonies correlated with the serum GOT level (r=0.96, p<0.001) but not with the contents of copper and 8-hydroxydeoxyguanosine in the liver of LEC rats. Ethanol treatment of hepatic cell lines also increased the rate of transcriptional slippage at the (A)(6) tract. These findings indicate that cellular damage is responsible for the increase in the rate of mutation at the transcriptional level, and suggest that cellular damage degrades transcriptional fidelity, thereby further impairing cellular functions.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Distinct prognostic values of p53 mutations and loss of estrogen receptor and their cumulative effect in primary breast cancers.

A total of 76 primary breast cancers were screened for p53 mutations using the yeast p53 functional assay, and the mutations were determined by DNA sequencing. Clonal mutations of p53 were detected in 30 tumors (39%). Immunohistochemical staining for nuclear p53 accumulation performed on the yeast assay-positive cases clearly differentiated missense mutations in the DNA binding domain (contact mutant; 17 cases) as positive stain and nonsense-type mutations or missense mutations that may affect 3D-structure of p53 protein (structural mutant; 13 cases) as negative stain. Enzyme immunoassay revealed loss of estrogen receptor in 36 tumors (50%). Prognostic values of p53 mutation and loss of estrogen receptor were evaluated after a median follow-up period of 44 months. p53 mutations were associated with a short overall survival (log rank test, p = 0.0319), whereas it was not related to disease-free (recurrence-free) survival. Contact mutants were associated with slightly shorter survival compared with structural mutants. Inversely, loss of estrogen receptor was associated with early recurrence (p = 0.0461) but not with short overall survival. The patients with tumors harboring both p53 mutation and loss of estrogen receptor had the poorest outcome (p = 0.0019 and 0.0075 for overall and disease-free survivals, respectively), suggesting independent and additive effects of the 2 factors. The independent role of the 2 factors was confirmed by a multivariate analysis using the Cox proportional hazard model stratified according to clinical tumor stages. Although preliminary, due to the small number of patients studied and the relatively short follow-up time, our results suggest that p53 mutations and loss of estrogen receptor cooperatively affect the prognosis of primary breast cancer patients.

Adult↗
PubMed2000

Correlation between magnetic resonance images and draining patterns in dural arteriovenous fistulas with leptomeningeal venous drainage.

OBJECTIVE: To compare abnormal intensity areas on intracranial magnetic resonance images (MRI) and the pattern of venous drainage in dural arteriovenous fistulas (DAVFs) with retrograde venous drainage. METHODS: Thirteen patients with retrograde venous drainage of DAVFs were divided into two groups based on the venous drainage pattern determined by detailed angiographic and MRI study. In group 1 there was an accessory route draining into another sinus besides the main draining sinus. In group 2 no such accessory route was present. RESULTS: In group 1 patients (n = 8), MRI detected no unusual intensity areas; 5 patients in this group had episodes of bleeding. Angiographically, in this group retrograde venous drainage tended to occur via multiple varices. On the other hand, none of the 5 group 2 patients experienced a bleeding episode. Angiographically, there was a low incidence of varices. On T2-weighted images, these patients had a hyperintensity area. Following treatment, these areas of abnormality disappeared on T2-weighted MRI. CONCLUSION: Among 13 patients with DAVFs which drained retrogradely, those with a variceal accessory route (Group 1, n = 8) had a higher incidence of haemorrhage. In patients without such an accessory route (Group 2, n = 5) abnormal signal intensity on MRI was indicative of venous congestion. Continuous-mode angiography and MRI study were useful in the precise identification of DAVFs with a venous drainage route.

Aged↗
PubMed2000

Somatic mutations of the APC gene in primary breast cancers.

APC gene mutations play an important role in the initiation step of colorectal carcinogenesis in both familial adenomatous polyposis (FAP) patients and non-FAP patients. Although the APC gene is expressed in most tissues, including the lung, liver, kidney, and mammary gland, its somatic mutations have rarely been found in primary tumors affecting these organs. We have developed a sensitive yeast-based assay for screening almost the entire coding region of the APC gene. By this method, we have been able to detect somatic mutations of the APC gene in 57% of colorectal cancers and none in non-small cell lung cancers. Interestingly, the assay detected somatic APC gene mutations in 18% of breast cancers, in which APC gene mutation was previously considered rare. In the breast cancers, most of the APC mutations were distributed outside the mutation cluster region that has been advocated for colorectal cancers. We also noted a difference in the mutation pattern of the APC between colorectal and breast cancers. In colorectal cancers, all base substitutions were observed at C residues (5 of 5), whereas in breast cancers the majority of them were found at G residues (4 of 5). Furthermore, APC mutations were observed at a significantly high frequency in advanced stages of primary breast cancers (TNM classification, P < 0.05; T category, P < 0.01). Our data suggest that the etiology of the APC mutations and their biological role in carcinogenesis may differ between colorectal and breast cancers.

Adenomatous Polyposis Coli↗
PubMed2000

Activated leukocyte cell adhesion molecule (ALCAM) and annexin II are involved in the metastatic progression of tumor cells after chemotherapy with Adriamycin.

Metastasis frequently occurs during and/or after chemotherapy resulting in failure. This suggests that inadequate chemotherapy promotes the emergence of more malignant tumor cells with metastatic potential. However, it is not determined how chemotherapy could promote the metastatic progression of tumor cells. In this study, we isolated highly metastatic clones from the tumors treated with ADR using an in vivo experimental model, in which non-metastatic tumor cells were inoculated s.c. in mice, treated with or without Adriamycin and then culture lines were re-established from the tumors. Then we isolated cDNAs for activated leukocyte cell adhesion molecule (ALCAM), osteopontin, and annexin II as candidates for metastasis-promoting genes with the use of a PCR-based subtraction method. Further we examined the metastatic potential of transfectants over-expressing ALCAM, osteopontin, or annexin II and combinations of them. Metastasis to the lung was observed in the mice where transfectants over-expressing ALCAM plus annexin II had been inoculated via tail vein. These results suggest that the over-expression of ALCAM and annexin II play a role in the metastatic progression after chemotherapy with ADR.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed2000

Idiopathic hypertrophic cranial pachymeningitis associated with a dural arteriovenous fistula involving the straight sinus: case report.

OBJECTIVE AND IMPORTANCE: Reports of idiopathic hypertrophic cranial pachymeningitis have increased as a result of advances in magnetic resonance imaging. This is the first documented case of idiopathic hypertrophic cranial pachymeningitis associated with a dural arteriovenous fistula involving the straight sinus. We discuss possible causes of the association and the treatment options. CLINICAL PRESENTATION: A 64-year-old man presented with a headache and visual disturbance. Gadolinium-enhanced T1-weighted magnetic resonance imaging demonstrated homogeneously stained meninges and prominent enhancement of the tentorium and falx. Angiograms demonstrated a dural arteriovenous fistula of the straight sinus. INTERVENTION: Although surgical excision of the straight sinus and subsequent corticosteroid therapy failed to relieve the patient's visual symptoms, subsequent surgical decompression of the optic nerve resulted in improvement and stabilization. CONCLUSION: Narrowing or occlusion of the tentorial sinuses and narrowing of the straight sinus by extensive dural fibrosis of the tentorium and falx, attributable in turn to idiopathic hypertrophic cranial pachymeningitis, may have resulted in the development of a dural arteriovenous fistula. We propose surgical decompression of the optic nerve as an alternative treatment during the active phase of the disease in patients who exhibit resistance to corticosteroid therapy.

Anti-Inflammatory Agents↗
PubMed2000

The mechanism of actinomycin D-mediated increase of Borna disease virus (BDV) RNA in cells persistently infected by BDV.

The transcriptional mechanism of Borna disease virus (BDV) has been poorly understood. We have analyzed transcription of the virus upon various stimuli in Madin-Darby canine kidney cells which were persistently infected by BDV (MDCK/BDV). Treatment with actinomycin D (ActD) increased the level of BDV RNA, shifting the size of RNA from 1.9 kb to 2.3 kb beginning 5 hr after the treatment. To understand the mechanism of this unique modulation of BDV RNA, we conducted several experiments. The RNA increase occurred at the stage in which synthesis of cellular intrinsic mRNA was intact, suggesting BDV does not compete with cellular transcriptional machinery for intrinsic RNA polymerase II. The BDV transcription was also enhanced by cycloheximide treatment, indicating that newly synthesized viral or cellular proteins are not necessary for viral transcription. However, a shift in the RNA size was not observed for cycloheximide-induced BDV RNA. The increase in viral transcription persisted during the cellular apoptotic process consequent to p53 gene accumulation beginning 1 hr after ActD treatment. Caspase inhibitors Z-VAD and DEVD-CHO repressed the apoptotic process but failed to block the increase in BDV transcription. In addition, adenovirus-mediated transduction of wild-type p53 did not alter the BDV transcription, indicating that the increase in BDV transcription was independent of the p53-mediated apoptotic process. Other various stimuli that evoke cellular signal transductions failed to alter BDV transcription. Agents inhibitory to topoisomerase except adriamycin failed to enhance BDV transcription, indicating that the increase in BDV transcription is not mediated by an inhibitory action to the topoisomerase II of ActD. Adriamycin showed an increase and size-shift of BDV RNA similar to ActD. These results suggest that intercalation of the viral genome itself with ActD is related to the stabilization of viral RNA and alteration of RNA size rather than secondary host cell changes.

Animals↗
PubMed2000

Successful treatment of a neonate with vein of Galen aneurysmal malformation.

We present a follow-up study on a 5-year-old boy who was born with vein of Galen aneurysmal malformation (VGAM) accompanied by extreme cardiovascular distress. He was successfully treated by the staged endovascular technique during the neonatal stage. Postoperative angiographic study confirmed complete occlusion of the VGAM and the establishment of normal brain perfusion. At 5 years of age, the child is growing normally without neurological deficits or developmental retardation. We suggest that the restoration of normal brain perfusion in neonates with VGAM can cause normal brain development.

Cardiomegaly↗
PubMed2000

Microcatheter intrathecal urokinase infusion into cisterna magna for prevention of cerebral vasospasm: preliminary report.

BACKGROUND AND PURPOSE: The feasibility of preventing vasospasm by intrathecal anterograde infusion of urokinase (UK) into the cisterna magna was studied in patients with recently ruptured aneurysms who had just undergone the placement of a Guglielmi detachable coil (GDC). METHODS: Immediately after complete embolization with the use of GDC-10 coils, 15 patients with Hunt and Hess neurological grades III and IV received 60 000 IU of UK in normal saline through a microcatheter advanced into the cisterna magna. UK infusion was repeated once or twice over a period of 2 to 3 days according to a decision based on CT evidence of a subarachnoid clot remaining in the cisterns. Before administering the last UK infusion, we obtained CT confirmation of almost complete clearance of clots in the basal cisterns. RESULTS: In all 15 patients, the microcatheter was advanced easily into the cisterna magna by use of the over-the-wire microcatheter technique. In 8 patients who received thrombolytic therapy within 24 hours of the ictus, there was almost complete clearance of the clot in the basal cisterns within 2 days of suffering the insult. When UK was injected at 24 to 48 hours after the insult, 7 patients manifested CT evidence of clearance at the latest 4 days after suffering the insult. In all 15 patients, CT scans obtained within 24 hours of the final UK administration showed complete resolution of clots in the basal cistern and almost complete resolution of clots in the basal interhemispheric fissure and bilateral proximal sylvian fissures. Although one patient developed a transient neurological deficit, no patients manifested permanent delayed neurological deficits as a result of vasospasm. Outcome assessment according to the Glasgow Outcome Scale, no less than 3 months after GDC placement, revealed good recovery in all patients, and none developed hydrocephalus requiring a shunt procedure. CONCLUSIONS: In patients with recently ruptured aneurysms, GDC placement followed by immediate intrathecal administration of UK from the cisterna magna may be a safe and reasonable means of preventing vasospasms and may result in improved treatment outcomes.

Adult↗
PubMed2000

Radiation-induced cerebrovasculopathy of the distal middle cerebral artery and distal posterior cerebral artery--case report.

A 15-year-old girl underwent partial removal of a pituitary adenoma followed by local irradiation of the brain with a total of 70 Gy through two lateral opposing ports. Twenty years later, she experienced frequent transient ischemic attacks with left sensory disturbance. Cerebral angiography revealed stenoses of the right distal middle cerebral artery (MCA) and the right distal posterior cerebral artery without net-like vessels. There was a severe decrease of vasoreactivity in the right hemisphere. Right superficial temporal artery (STA)-MCA anastomosis was performed. Her neurological deficits were resolved and perfusion reserve capacity had markedly improved 6 months later. We recommend STA-MCA anastomosis in such cases.

Adolescent↗
PubMed2000

Histopathological study of venous aneurysms in patients with dural arteriovenous fistulas.

OBJECT: Of all intracranial dural arteriovenous fistulas (DAVFs), those with cortical venous drainage associated with cortical venous ectasia or varices are predisposed to an aggressive course and produce progressive neurological symptoms or hemorrhages. The authors undertook a histological examination of venous aneurysms and arterialized veins in the proximity of these aneurysms that had been surgically removed in patients with DAVFs. METHODS: Surgical specimens were obtained in eight patients. The excised venous aneurysms and the arterialized veins in their proximity were stained using hematoxylin and eosin, van Gieson's elastic, and Masson's trichrome stain. Immunostaining was also performed for alpha smooth-muscle actin, desmin, and factor VIII antigen. Five of the patients had presented with venous hypertension, and three had intracranial hemorrhages. The arterialized vein obtained in the proximity of the venous aneurysm exhibited local irregular intimal thickening; the internal elastic lamina (IEL) was grossly preserved. All venous aneurysms in patients with venous hypertension manifested medial thickening and local intimal thickening with loss of IEL; the thickness of the wall was relatively uniform. In contrast, the wall thickness of venous aneurysms in patients with hemorrhage was extremely irregular and there was no clear delineation between the media and the intima. In media with complete disappearance of IEL, there was scant muscle tissue. CONCLUSIONS: Degenerative changes in venous aneurysms in patients with hemorrhage were much greater than in patients with venous hypertension, possibly because hemorrhages result from a more complicated interplay of anatomical, hemodynamic, and degenerative factors.

Aged↗
PubMed1999

A functional and quantitative mutational analysis of p53 mutations in yeast indicates strand biases and different roles of mutations in DMBA- and BBN-induced tumors in rats.

In order to analyze the mutational events and to understand the biological significance of the p53 gene in chemical carcinogenesis, we applied a new yeast-based p53 functional assay to ovarian tumors induced by 7, 12-dimethylbenz[a]anthracene (DMBA), as well as to transitional cell carcinomas of the urinary bladder induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in rats. The assay demonstrated that 15 of 19 DMBA induced tumors harbored clonal p53 mutations, which is consistent with the expectations of the "clonal expansion" hypothesis. The majority of the mutations were purine (AG) to pyrimidine (CT) transversions (12/19) on the non-transcribed (sense) strand (NTS), which is likely to be due to depurination created by DMBA adduct formation on the NTS. In contrast, we found no pyrimidine to purine [corrected] transversion on the NTS. After cessation of BBN treatment, BBN-induced multifocal lesions in the bladder contained heterogeneous p53 mutations at an early stage. In the later stage, however, clonal p53 mutations were identified in 4 out of 7 bladders analyzed, conforming with the concept of "field cancerization". The observed base substitutions were G-->A (1/6) or C -->T transitions (2/6), and mutations at T (3/6) on the NTS in clonal mutations, together with non-clonal mutations, showing a preference of C-->T to G-->A (17 vs. 0). Thus, preferential repair was found in the transcribed strand of the p53 gene, whether modified by DMBA or by BBN carcinogens. Very similar mutation patterns were observed between clonal and non-clonal mutations in the DMBA- and BBN-induced tumors, indicating that the rat yeast p53 functional assay can be a potential tool for the characterization of in vivo mutation patterns of p53, when modified by chemical carcinogens.

9,10-Dimethyl-1,2-benzanthracene↗