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Biomedical subjects

M Iwasaki

Publications and source records attributed to M Iwasaki.

At least 127 records · Page 7Linked to original sources

Fission yeast Eso1p is required for establishing sister chromatid cohesion during S phase.

Sister chromatid cohesion is essential for cell viability. We have isolated a novel temperature-sensitive lethal mutant named eso1-H17 that displays spindle assembly checkpoint-dependent mitotic delay and abnormal chromosome segregation. At the permissive temperature, the eso1-H17 mutant shows mild sensitivity to UV irradiation and DNA-damaging chemicals. At the nonpermissive temperature, the mutant is arrested in M phase with a viability loss due to a failure to establish sister chromatid cohesion during S phase. The lethal M-phase arrest phenotype, however, is suppressed by inactivation of a spindle checkpoint. The eso1(+) gene is not essential for the onset and progression of DNA replication but has remarkable genetic interactions with those genes regulating the G(1)-S transition and DNA replication. The N-terminal two-thirds of Eso1p is highly homologous to DNA polymerase eta of budding yeast and humans, and the C-terminal one-third is homologous to budding yeast Eco1p (also called Ctf7p), which is required for the establishment of sister chromatid cohesion. Deletion analysis and determination of the mutation site reveal that the function of the Eco1p/Ctf7p-homologous domain is necessary and sufficient for sister chromatid cohesion. On the other hand, deletion of the DNA polymerase eta domain in Eso1p increases sensitivity to UV irradiation. These results indicate that Eso1p plays a dual role during DNA replication. The C-terminal region acts to establish sister chromatid cohesion, and the N-terminal region presumably catalyzes translesion DNA synthesis when template DNA contains lesions that block regular DNA replication.

Acetyltransferases↗

Seronegative HIV-2 carriers in India.

The discordant cases of seronegative, but culture and proviral HIV-2 DNA positive were found in Mumbai, India. This was corroborated by the successful isolation of HIV-2-RNA in culture medium, HIV-2 cDNA sequence determination and the detection of the antigen. The sequence of the isolated HIV-2 genomic RNA does not seem to be altered to the extent that the change will alter antibody binding. Furthermore, antibody from the same individual (even at 8 months from initial sampling) from whom HIV-2 was isolated did not react with the antigen of this strain. Those evidences imply that extremely low or non-production of the antibody may be due to suboptimal immune stimulation due to extremely slow HIV-2 replication. This low virus-load may be responsible for the negative antibody results in the HIV-2 carriers.

Carrier State↗

Effectiveness of the fold plication method in lung volume reduction surgery.

OBJECT: The fold plication method is a new operative procedure for lung volume reduction surgery whereby the target area is obliterated by plicating the folded tissue using a knifeless stapler, without the use of bovine pericardium. The effectiveness of this new method was evaluated in patients with advanced pulmonary emphysema. PATIENTS AND METHODS: Two weeks before and 6 months after surgery, pulmonary function, static lung compliance, maximal esophageal pressure, maximal inspiratory and expiratory mouth pressures, 6-min walking distance and the Borg scale were determined in twenty consecutive patients who underwent video-assisted thoracoscopic unilateral surgery. RESULTS: There was an increase in forced expiratory volume in one second (31%), forced vital capacity, peak expiratory flow rate and maximal voluntary ventilation, and a decrease in functional residual capacity (-16%) measured by plethysmograph. Static lung compliance decreased, and maximal esophageal pressure, and maximal inspiratory and expiratory mouth pressures increased. The 6-min walking distance increased (20%) and the Borg scale decreased (5.9 to 3.5). CONCLUSION: The results compare favorably with those obtained with other methods. Thus, the fold plication method could be considered an alternative procedure for lung volume reduction surgery.

Aged↗

Indications for shunting in patients with idiopathic normal pressure hydrocephalus presenting with dementia and brain atrophy (atypical idiopathic normal pressure hydrocephalus).

The indications for shunt operation in patients with idiopathic normal pressure hydrocephalus accompanied by brain atrophy (atypical idiopathic normal pressure hydrocephalus: AINPH) were investigated in 25 patients who satisfied the diagnostic criteria and underwent ventriculoperitoneal (VP) shunting. All patients had no apparent history of intra- or extracranial disease; dementia and gait disturbance as the main complaints; moderate to severe cerebral atrophy and ventricular dilatation and at least periventricular low density around the anterior horn on computed tomography; normal cerebrospinal fluid (CSF) pressure and filling of ventricles or cortical surface space with contrast medium at 24 hours on cisternography. The 15 male and 10 female patients were aged 47-83 years (mean 60.4 years). VP shunting was effective in 12 improved patients and not effective in 13 unimproved patients according to NPH grading. Pathological pressure wave on epidural pressure monitoring was observed in eight of 12 improved patients, but none of 13 unimproved patients. CSF outflow resistance was 35.33 +/- 11.16 mmHg/ml/min in improved patients and 9.12 +/- 3.51 mmHg/ml/min in unimproved patients. Preoperative serum alpha-1-antichymotrypsin value (alpha-1-ACT) was 42.02 +/- 8.64 mg/dl in improved patients and 61.72 +/- 11.03 mg/dl in unimproved patients. Alpha-1-ACT over 55 mg/dl occurred only in unimproved patients. Cerebral arteriovenous difference of oxygen content value (c-AVDO2) before and after surgery was 6.34 +/- 0.9 ml% and 5.91 +/- 0.78 ml% in improved patients and 4.75 +/- 1.85 ml% and 4.81 +/- 1.73 ml% in unimproved patients, respectively. The two cases with preoperative c-AVDO2 value over 8.5 ml% were both unimproved. Mean cerebral blood flow value before and after surgery was 23.51 +/- 4.20 ml/100 g/min and 45.22 +/- 8.11 ml/100 g/min in improved patients and 21.77 +/- 5.12 ml/100 g/min and 24.82 +/- 4.97 ml/100 g/min in unimproved patients, respectively. Cerebral atrophy in improved patients is caused by a cerebral circulation disturbance defined as a cerebral blood flow of penumbra or more due to cerebral arteriosclerosis, etc. A flow-chart of indications of shunt surgery for AINPH was prepared based on the results of the present study.

Aged↗

The development of peritumoral stroma required for IL-12 induced tumor regression depends on the T cell/IFN-gamma-involving host-tumor interaction.

T cell migration into tumor masses is a critical process in the scenario of IL-12-induced tumor regression. Our previous study showed that this depends on the development of peritumoral stroma prior to IL-12 therapy. The present study investigated the regulation of the development of peritumoral stroma in comparison with tumor-parenchymal stroma. In the OV-HM and CSA1M tumor models, tumor regression associated with T cell migration was induced following IL-12 treatment. Both OV-HM and CSA1M tumor masses growing in syngeneic mice developed peritumoral stroma before IL-12 treatment. However, peritumoral stroma was not observed in these two types of tumor masses generated in nude mice, T cell-depleted syngeneic mice, anti-IFN-gamma mAb-treated mice or IFN-gamma-deficient mice. In contrast, parenchymal stroma formation did not appear to be affected because tumors generated in these groups of mice exhibited rather higher growth rates than those of tumors in normal syngeneic mice. Importantly, the lack of peritumoral stroma in tumor masses was associated with the failure of T cells to migrate to these tumor masses: splenic T cells prepared from IL-12-treated tumor-bearing mice migrated into the corresponding tumor mass growing in untreated syngeneic recipient mice, whereas portions of the same donor cells failed to migrate into the above stroma-negative tumor masses. These results indicate that the development of peritumoral and parenchymal stroma is differentially regulated; there exist functional differences in the two types of stroma; and the formation of peritumoral stroma requires components of the host's immune system such as IFN-gamma and T cells.

Animals↗

[Spinal dermoid cyst secondary to myelomeningocele repair: a case report].

Dermoid and epidermoid tumors arise from the invagination of epidermal elements into the neural tube during the embryonic period. However, many studies have reported that dermoid and epidermoid tumors occur 5 to 10 years after the first operation on myelomeningocele patients. A seven-year-old male with myelomeningocele which had been repaired in his neonatal period, presented leg pain and deterioration of gait disturbance and urinary incontinence. Neuroradiological examinations revealed a spinal dermoid cyst at the repaired myelomeningocele and tethered spinal cord. We removed the tumor and untethered the tethered spinal cord. Postoperatively, the patient's leg pain, gait disturbance and urinary incontinence improved immediately. Inappropriate surgical treatment of spina bifida may cause a second lesion, which leads to tethered-cord syndrome. We suggest that proper surgical treatment, early checkup and neuroradiological evaluations are very important for spina bifida patients who show signs of neurological deterioration. For the best treatment, neurological, urological and orthopedical follow-up study after the first repair operation is necessary.

Child↗

[A case of angiographically occult arteriovenous malformation with metaplasia (so-called brain stone)].

The patient was a 69-year-old female. Right hemiparesis occurred on April 25, 1996, and then was relieved a day later. Because headache (dull pain in the left) persisted subsequently, she consulted our department on April 26. Head CT showed, without enhancement effect, osseous high density on the surface of the left frontal area. MRI showed high intensity on T1 and low intensity on T2 with flow-void like findings. Cerebral angiography showed a pooling of contrast medium in the same region. 123I-IMP-SPECT revealed reduced cerebral blood flow in the left frontal and parietal lobes just under the same region. On June 11, the patient underwent surgery during which a tumor with arachnoid hypertrophy was extracted en block. Histopathologically, there were abnormal blood vessels with elastic fibers, expanding to an ossified site, and AVM accompanying ossification was thus diagnosed. Postoperative 123I-IMP-SPECT showed improved cerebral blood flow in the left frontal and parietal lobes. The patient was discharged on June 22. The TIA pathologic condition, a symptom of its onset, was considered attributable to cerebral blood flow steal due to AVM.

Aged↗

[Clinical characteristics and indications for shunting in patients with idiopathic normal pressure hydrocephalus with brain atrophy (atypical idiopathic normal pressure hydrocephalus)].

PURPOSE: To clarify clinical characteristics of atypical idiopathic normal pressure hydrocephalus (AINPH) and indications for shunt operations. SUBJECTS AND METHODS: Subjects examined in the present study included 65 patients who satisfied the following 4 diagnostic criteria of AINPH and underwent V.P shunt with Medos type shunt system; set pressure: epidural standard pressure x 13.6 - 20 mmH2O (omission of a figure in the first place). The diagnostic criteria were: 1) no apparent history of intra- or extra-cranial disease; 2) dementia was present as a main complaint; 3) the presence of moderate to severe cerebral atrophy and ventricular enlargement and PVL around the anterior horn on CT scans; 4) normal cerebrospinal pressure and filling of ventricles or subarachnoid space with contrast medium at 24 hours on cisternography. The patients were aged 49-83 with the mean age of 62.9 years; the ratio of male to female was 37:28. They were categorized as shunt-effective (group E: 36 cases) or non-shunt-effective (group NE: 29 cases), and the following parameters in both groups were compared: 1. clinical characteristics: 2. the presence or absence of pressure wave (PW) during preoperative continuous epidural pressure measurement (EDPM) 3. CSF outflow resistance (Ro) 4. preoperative serum alpha-1-antichymotrpsin (alpha-1-ACT) 5. cerebral arteriovenous difference of oxygen content (c-AVDO2) before and after surgery 6. mean cerebral blood flow (mCBF; 99mTc-HMPAO-SPECT) before and after surgery. RESULTS AND CONCLUSIONS: 1. Group E had a shorter duration between symptom onset and hospital visit (within 16 months and showed hyporoluntary and hyporeactivity as their main complaints associated with gait disturbance; the time course of symptoms was classified as suddenly progressing and fluctuating in many cases. Group NE had a relatively longer duration between symptom onset and hospital visit and showed activeness, wandering, nervousness and quick temper as their main complaints; the time course of symptoms was classified as progressing in many cases. 2. PW-positive cases were all included in group E. but some PW-negative cases were also observed in group E. 3. Ro was significantly higher in group E (p < 0.01), and cases with a Ro value over 20 mmHg/ml/min. were all included in group E. 4. alpha-1-ACT was significantly lower in group E (p < 0.05), and cases with an alpha-1-ACT value over 55 mg/dl were all included in group NE. 5. Although preoperative c-AVDO2 was significantly higher in group E (p < 0.05), cases with a c-AVDO2 value over 8.5 ml% were all included in group NE. c-AVDO2 values were within 5-8.5 ml% in all cases of group E. 6. mCBF significantly increased after surgery in group E (p < 0.001). 7. It was confirmed that cerebral atrophy in group E on AINPH is caused by a cerebral circulation disturbance defined as a cerebral blood flow of penumbra or more due to cerebral arteriosclerosis, etc. 8. A flowchart of indications for shunt surgery for AINPH was prepared based on the results of the present study.

Aged↗

Is it permissible to omit mediastinal dissection for peripheral non-small-cell lung cancers with tumor diameters less than 1.5 cm?

BACKGROUND: Recently the pros and cons of limited surgery for small-sized peripheral non-small-cell lung cancers (PNSCLCs), such as omission of mediastinal dissection, etc., have been vigorously debated. We analyzed whether hilar/mediastinal lymph node metastases were present in 30 small-sized PNSCLCs. MATERIAL AND METHODS: In the nine years from 1990 to 1998, 294 lung cancer patients underwent lobectomy or pneumonectomy combined with hilar/mediastinal dissection in the Tokai University Hospital. Thirty of these patients diagnosed as having cT1N0M0 PNSCLC with tumor diameters of 1.5 cm or less by computed tomography, are evaluated in this article. RESULTS: The 30 PNSCLC patients consisted of 14 males and 16 females with a mean age of 61 +/- 9 years. Twenty six patients (87%) had no hilar nor mediastinal lymph node metastases (pN0), one patient (3%) had a hilar lymph node metastasis (pN1), and three patients (10%) had mediastinal lymph node metastases (pN2). CONCLUSIONS: Mediastinal lymph node metastases were histologically observed in 3 (10%) of 30 PNSCLC patients with tumor diameters of 1.5 cm or less. Our results show that mediastinal dissection is still necessary even for small-sized lung cancers.

Carcinoma, Non-Small-Cell Lung↗

[Clinical training and home therapy in our clinic].

Since 1986, we have practiced clinical training. In this training, the physician trainee acts as the head of our clinic, managing programs including the medical teams for outpatient clinics and home therapy. Our home therapy started in 1975 and successive resident trainees have held conferences, cooperation between hospitals and clinics between clinics, and also held home patient and family parties. In our clinical training, therefore, the resident can effectively gain generalized clinical abilities.

Aged↗

Low-Temperature Synthesis of Nanometer-Sized Crystalline TiO2 Particles and Their Photoinduced Decomposition of Formic Acid.

Anatase TiO2 particles with an average size of 2.7 nm in an as-grown state were obtained below 373 K from an H2O-EtOH mixed solution of TiOSO4 by a facile liquid phase method. The volume ratio of H2O to EtOH was revealed to be the key for crystallinity of the particles. The as-grown particles prepared from the H2O-EtOH solution (H2O/EtOH (mL/mL) = 150/100) showed a high photoreactivity in the TiO2 photoinduced decarboxylation of HCOOH under a deaerated condition. In contrast, under an aerated condition, the rate of the reaction increased with an increase in calcining temperature (Tc) due to the improvement of anatase crystallinity, going through a maximum at Tc = 873 K. Copyright 1999 Academic Press.

Journal Article↗

Hypermethylation of the Estrogen Receptor Alpha Gene Is Not Related to Lack of Receptor Protein in Human Breast Cancer.

BACKGROUND: Expression and transcriptional activity of genes are regulated byseveral factors, including DNA methylation. We examined the frequency of DNA hypermethylation at two nucleotide positions, the proximal promoter region (PPR) in exon 1 and the distal promoter region (DPR) in exon 1' of the estrogen-receptor alpha (ER alpha) gene in human breast cancer, and the correlation between ER and progesterone receptor (PgR) status. METHODS: The frequency of hypermethylation of PPR and DPR in 124 breast cancerswas examined by the semiquantitative competitive polymerase chain reaction (COM-PCR) assay with restriction enzymes. ER and PgR proteins were analyzed by enzyme immunoassay (EIA; fmol/mg) to determine whether DNA hypermethylation influences the status of either protein. RESULTS: There were no significant differences in ER protein status between DNAmethylated and unmethylated groups for either PPR (71.2 +/- 190.1 versus 60.7 +/- 88.4) or DPR (70.0 +/- 183.6 versus 60.9 +/- 89.3). There was a significant differencein PgR protein status between these two groups for PPR (46.8 +/- 67.1 versus 169.1 +/- 394.9, P< 0.01). When one positional methylation was regarded as the criterion for hypermethylation, the frequency of hypermethylation in the ER(+)PgR(-)phenotype was significantly higher than in the ER(+)PgR(+), ER(-)PgR( +) and ER(-)PgR(-) phenotypes (72.7% versus 31.3%, 40.0% and 28.6%, P< 0.01). CONCLUSION: Hypermethylation of the 5'-upstream side of the ER alpha gene did notcorrelate with lack of ER, but did correlate with lack of PgR, and particularlywith the expression of the ER(+)PgR(-) phenotype. We conclude that DNA hypermethylation of PPR and DPR in the Er alpha gene reflects the expression of the ER target gene rather than the ER gene itself and may account for anti-estrogen resistance in ER-positive breast cancer.

Journal Article↗

Application of the fold plication method for unilateral lung volume reduction in pulmonary emphysema.

BACKGROUND: Unilateral lung volume reduction procedures are used to treat pulmonary emphysema. The most significant technical problem with this operation is an air leak from the pulmonary stump. Bovine pericardium has been used to prevent air leaks but is associated with interstitial pneumonia and a high cost. METHODS: The fold plication method was devised to prevent postoperative air leaks to avoid interstitial pneumonia, and to decrease cost. This technique was applied in 20 consecutive patients with emphysema who underwent a unilateral lung volume reduction operation via a thoracoscopic two windows approach. RESULTS: The operative time was approximately 1 hour. There was minimal postoperative bleeding, no persistent air leaks, and no evidence of pneumonia. Pulmonary function improved in all patients. CONCLUSIONS: The unilateral fold plication method is an economical and safe alternative to bovine pericardial patching after lung volume reduction operation to prevent stump air leaks.

Adult↗

Determination of estrogen receptor in primary breast cancer using two different monoclonal antibodies, and correlation with its mRNA expression.

Estrogen receptor (ER) protein status was investigated in the MCF-7 cell line and 70 invasive ductal carcinomas of the breast. This was achieved by immunohistochemical assay (IHA) using two different monoclonal antibodies (ER-1D5 and AER311), which are able to recognize either the amino or carboxyl terminal. The staining results were assessed in terms of index score, and compared with the ERalpha mRNA expression, which was determined by reverse transcription-polymerase chain reaction for the positions of exons 5 and 7. MCF-7 showed similar immunoreactions with both antibodies, and expressed the wild-type (WT) ER mRNA coexpressing deletions of exons 5 and 7. Although there was a significant difference between the ER-1 D5 and AER311 indices in the tissue samples (20.5 +/- 27.2 and 5.7 +/- 16.4; P < 0.001), in the majority of cases ER mRNA expression patterns were similar to that of MCF-7, and WT ER mRNA was expressed in all cases that yielded PCR products. It was concluded that a number of palpable breast cancers lack the carboxyl terminal of the ER protein, regardless of WT ER mRNA expression. These results suggest that the incidence of WT ER mRNA in such cancers is lower than that in the MCF-7 cell line, or that WT ER is less stable.

Alternative Splicing↗

Illegitimate recombination induced by overproduction of DnaB helicase in Escherichia coli.

Illegitimate recombination that usually takes place at a low frequency is greatly enhanced by treatment with DNA-damaging agents. It is thought that DNA double-strand breaks induced by this DNA damage are important for initiation of illegitimate recombination. Here we show that illegitimate recombination is enhanced by overexpression of the DnaB protein in Escherichia coli. The recombination enhanced by DnaB overexpression occurred between short regions of homology. We propose a model for the initiation of illegitimate recombination in which DnaB overexpression may excessively unwind DNA at replication forks and induce double-strand breaks, resulting in illegitimate recombination. The defect in RecQ has a synergistic effect on the increased illegitimate recombination in cells containing the overproduced DnaB protein, implying that DnaB works in the same pathway as RecQ does but that they work at different steps.

Bacterial Proteins↗