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Biomedical subjects

H Iwata

Publications and source records attributed to H Iwata.

At least 127 records · Page 7Linked to original sources

Expression of estrogen receptor alpha exon 5 and 7 deletion variant in human breast cancers.

BACKGROUND: An exon deletion variant of estrogen receptor (ER) mRNA has been reported, as one of the possible mechanisms of loss of ER function. METHODS: We examined the expression of exons 3, 5, and 7 in ER alpha mRNA and the frequency of exon deletion variant expression in 64 cases of human breast cancers and in 8 non-cancerous breast tissues using reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Approximately the same amount of wild-type (wt) mRNA was detected in all the non-cancerous breast tissues. In cancers, expression of wild-type exon 3 (w3), exon 5 (w5), and exon 7 (w7) was detected in 93.5%, 93.5%, and 91.3% of ER alpha protein (pER) positive cases, respectively, and 27.8%, 38.9%, and 44.4% in negative cases, respectively (p < 0.0001, p = 0.0035, and p = 0.0002). Although the variants for exon 5 (d5) and 7 (d7) were detected in both non-cancerous and cancerous tissues respectively, the variant for exon 3 was not detected at all. Comparatively, the ratio of d5/w5 was significantly higher in pER positive and progesterone receptor protein (pPgR) negative cases. CONCLUSIONS: We suspect that the exon 5 deletion does not work as a dominant positive.

Breast↗

A case of metastatic breast cancer achieving complete response by combination therapy with 5'-deoxy-5-fluorouridine and cyclophosphamide.

Recently there have been several reports on the effectiveness of combination chemotherapy with 5'-deoxy-5-fluorouridine (5'-DFUR) and cyclophosphamide (CPA) for treating recurrent breast cancer. We report a case in which treatment of local recurrence and lung metastases responded was remarkably effective by this combination chemotherapy. A 45-year-old woman underwent modified radical mastectomy for left breast cancer (T2N0M0) three years previously. Involvement of a left supraclavicular lymph node (ScLN) and multiple lung metastases were revealed 2 years and 6 months after the operation. First, we opted for systemic endocrine therapy with local irradiation for the lung metastases and ScLN. However the lung metastases were found to have increased on chest x-ray 2 months after treatment, showing progressive disease (PD). A locally recurrent new lesion sized 2 x 2 cm had also developed. Thus, we changed the treatment to combination chemotherapy with 5'-DFUR 800 mg/body and oral CPA 100 mg/body once a day. The lung metastases had disappeared on chest x-ray and the local recurrence was not palpable after 7 weeks of the new treatment. Thymidine phosphorylase (dThdPase) immunostaining of the primary tumor was strongly positive in almost all cancer cells. We discuss the mechanism of the increased efficacy of combination chemotherapy with 5'-DFUR and CPA.

Antineoplastic Combined Chemotherapy Protocols↗

Clinical and pathologic factors predicting axillary lymph node involvement in breast cancer.

The diagnosis of axillary disease remains a challenge in the management of breast cancer and is a subject of controversy. In 1998, the Japanese Breast Cancer Society conducted a study assessing axillary lymph node involvement in breast cancer. The study included (a) clinical assessment by pre-operative imaging modalities, (b) histologic assessment for peritumoral lymphatic invasion, (c) biologic assessment by gelatinolytic activity using film in situ zymography, and (d) sentinel lymph node (SLN) biopsy. Clinical assessments by CT, PET, and US as well as biologic assessment were limited in their ability to detect axillary lymph node disease, although these imaging techniques may be useful to exclude node-positive patients from the need for SLN biopsy. Histologic assessment for peritumoral lymphatic invasion was useful, particularly for detecting false-negative cases by SLN biopsy. Nevertheless, the utility of SLN biopsy in assessing axillary nodal status was confirmed. Axillary lymph node dissection (ALND) can be avoided in patients with a small tumor and a negative SLN. However, further studies will be required to investigate the value of SLN biopsy for predicting regional control and survival before it can replace routine ALND as the optimal staging procedure for operable breast cancer.

Axilla↗

Natural history of unreduced congenital dislocation of the hip in adults.

The natural history of 33 patients with 43 unreduced congenital dislocations of the hip was reviewed. The average age at the first consultation was 50 years. Four were men and 29 were women. Ten patients had bilateral and 23 unilateral complete dislocation. Average follow-up lasted 9.2 years. At the final follow-up 23 hips and 18 knees were painful. Lumbago was observed in 6 of 15 patients under the age of 50 and in 14 of 18 patients over the age of 50 at the final follow-up. The average Harris hip scores at the first and final consultations were 69 and 70, respectively. The average dislocation index was increased in the standing more than in the lying position. In unilaterally dislocated hips the average femorotibial angles in the ipsilateral and contralateral knees to the dislocated hip were 172 and 179 deg, respectively. Lumbar degenerative scoliosis of more than 5 deg was observed in 16 patients.

Female↗

Passive terminal extension causes anterior tibial translation in some anterior cruciate ligament-deficient knees.

The purpose of the present study was to accurately measure anterior tibial translation during passive terminal extension (ATT-PTE) in anterior cruciate ligament (ACL)-deficient knees, and to investigate correlations between various characteristics of such knees and the magnitude of ATT-PTE. The subjects were 79 patients with unilateral ACL-deficient knees and little flexion contracture. All patients were confirmed to have ACL injury of one knee by arthroscopy. Lateral radiographs of the bilateral knees in passive terminal extension were compared, and ATT-PTE was measured using an original superimposition method. The inter-observer and intra-observer reproducibility of measurement was significantly greater for this method than for the method without superimposition. In 42 of the 79 patients (53%), ATT-PTE was greater than 1 mm, while it was greater than 4 mm in 15 patients (19%). ATT-PTE was significantly larger in patients with a large anterior displacement difference (as measured with the KT-1000 arthrometer) (ATT-KT), a long period since injury, a history of reinjury, injury to the meniscus, and the presence of gross pivot shift. On the other hand, ATT-KT was equal to or greater than 2.5 mm in all 79 patients and showed no significant correlation with the time since initial injury, history of reinjury, on injury to the meniscus.

Adolescent↗

Osteophyte of the femoral head after transtrochanteric rotational osteotomy.

The relationship between change in the shape of the femoral head and the clinical results after transtrochanteric rotational osteotomy for osteonecrosis of the femoral head was investigated. Fifty-six hips in 50 patients, followed for at least 2 years, showed no progressive collapse and no osteoarthrotic change during that time. The growth of a superolateral osteophyte of the femoral head was observed postoperatively at a higher rate with progression of the preoperative stage. Excessive restoration of the rotated necrotic lesion of the femoral head was observed at a higher rate in hips with the growth of the superolateral osteophyte. The total Japanese Orthopaedic Association score at final follow-up in hips with these shape changes of the femoral head was significantly inferior to the score in hips without these changes. There was a tendency for hips with a low ratio of intact articular surface of the femoral head in the weight-bearing area to the acetabulum just after surgery to manifest these shape changes. Although such changes of the femoral head were considered to represent remodeling to stabilize the hip joint, excessive remodeling could worsen the clinical results.

Adolescent↗

Non-adhesive cyanoacrylate as an embolic material for endovascular neurosurgery.

Endovascular neurosurgery is now becoming available as one of strategies for the treatment of cerebro-spinal arterio-venous malformations and aneurysms. For this treatment, a microcatheter is advanced into or close to a lesion and then an embolic material is administered through it to obliterate the lesion. N-butyl-2-cyanoacrylate (NBCA) has preferentially been used as an embolic material in Europe and America. However, its exceptionally strong adhesive force sometimes causes adhesion between the tip of the microcatheter and the artery. In this study, a new non-adhesive cyanoacrylate, isostearyl-2-cyanoacrylate (ISCA), was developed. It carries a long hydrophobic side isostearyl group with lower reactivity and adhesion than other cyanoacrylates. Its polymerization rate is, however, too low to obliterate a vascular lesion with a rapid blood flow. To increase the polymerization rate. ISCA was mixed with NBCA. As a result, the adhesive force of the mixture became extremely low, compared with that of NBCA. The viscosity of the mixture was low enough to allow its' use as an embolic material. Tissue reactions against the mixture was milder than those against NBCA. Radio-angiography became possible by mixing further with Lipiodol. The evaluation of this new embolic material with a rabbit renal artery showed that the obliteration effect of the mixture of ISCA and NBCA was excellent to use as an embolic material for clinical applications.

Animals↗

Surface modification of polyethylene balloon catheters for local drug delivery.

Local drug delivery is an attractive approach to the associated problems of percutaneous transluminal coronary angioplasty (PTCA), including arterial injury. The objective of the present research was to deliver a high concentration of a potent anti-thrombin agent, argatroban (ARG), to the vessel wall in order to reduce arterial injury. Local delivery was accomplished by the ionic attachment of drug particles to a modified balloon surface. Surface graft polymerization of ionic monomers to a high-density poly(ethylene) (PE) substrate was performed utilizing ultra-violet (UV) methods. Acrylic acid (AAc) and 2(dimethylamino) ethyl methacrylate (DMAEMA) were successfully grafted onto PE surfaces. Surface grafting was verified by contact angle, X-ray photoelectron spectroscopy, and zeta potential measurements. The amount of ARG adsorbed onto the modified PE surface was highly dependent on the pH of the drug media for both anionic and cationic grafted monomers. The efficacy of local drug delivery to the arterial wall was analyzed using drug-immobilized PE balloon catheters in the rabbit common carotid artery model. High concentrations of ARG (280 nmol/g tissue) were found within the ballooned arterial segment immediately after angioplasty, followed by a decrease after blood flow was restored.

Acrylates↗

Identification of novel cytochrome P450 1A genes from five marine mammal species.

Marine mammals, being endangered by the chronic exposure of hydrophobic environmental contaminants as an assorting result of global pollution, are especially focused as indicators for organochlorine pollution. The use of contaminant-induced xenobiotic metabolizers, particularly P450 (CYP) 1A, in marine mammals can be effective as potential biomarkers of the contaminant exposure and/or toxic effects. In this study, we identified the first marine mammalian CYPs. Six novel CYP1A cDNA fragments were cloned from the livers of marine mammal species, minke whale (Balaenoptera acutorostrata), dall's porpoise (Phocoenoides dalli), steller sea lion (Eumetopias jubatus), largha seal (Phoca largha), and ribbon seal (Phoca fasciata) by the method of reverse transcription/polymerase chain reaction (RT/PCR); two distinct fragments were from steller sea lion and one fragment each was obtained from the other species. Five of the fragments, one from each species, were classified in the subfamily of CYP1A1, and the other fragment cloned from steller sea lion was designated CYP1A2. Degenerate PCR primers were used to amplify the fragments from liver cDNAs. The deduced amino acid sequences of these fragment CYP1As showed identities ranging from 50.0 to 94.3% with other known vertebrate CYPs in the subfamily of CYP1A, including those from fish, chicken, and terrestrial mammals. The isolated fragments were used to construct a molecular phylogeny, along with other vertebrate CYP1A cDNAs cut down in size to the corresponding region of 265 bp in which those newly determined fragments were cloned. This phylogenetic analysis by the maximum parsimony method using the PHYLIP program suggests two distinct evolutional pathways for aquatic mammalian CYP1As, compatible to a conservative taxonomy. Pinniped genes are clustered together with dog gene, forming a carnivore group, and cetaceans form another branch. Identification of CYP1A genes in marine mammals will be an introductory step to provide new insights into the metabolic or toxicological functions of CYP1As in these animals.

Amino Acid Sequence↗

Siblings of Schwartz-Jampel syndrome with abnormal muscle computed tomographic findings.

Schwartz-Jampel syndrome (SJS) is a disorder characterized by myotonia, joint contractures, skeletal abnormalities, facial dysmorphism and growth retardation. We present two boys of ages 4 and 8 years with SJS. Their clinical, electromyographic and histopathological findings were similar to those described, except for computed tomography (CT) images that revealed diffuse high attenuation in sternocleidomastoid muscles and low attenuation in the paraspinal, quadriceps, sartorius, soleus and gastrocnemius muscles. This is the first report describing abnormal muscle CT findings associated with SJS. Additional studies of muscle CT might help to improve understanding of the pathogenesis of SJS.

Child↗

Gelatinolytic activity of matrix metalloproteinase-2 and -9 in oesophageal carcinoma; a study using in situ zymography.

In this study, we investigated the activity of matrix metalloproteinase (MMP)-2 and -9 by gelatine zymography, immunostaining and in situ gelatine zymography in 30 oesophageal squamous-cell carcinomas. The gelatinolytic activity in situ was detected in all cases with different patterns of localisation. Significant gelatinolysis by stromal cells adjacent to tumour nests was found in 12 cases. Strong gelatinolytic activity appeared within the tumour nest itself in 13 cases. In the other 5 cases, both stromal cells and tumour cells showed the gelatinolytic activity. Gelatine zymography demonstrated a correlation between vascular invasion and activation of MMP-9. It also demonstrated a correlation between lymph node metastasis, lymphatic or vascular invasion and activation of MMP-2. These results suggest that MMPs play an important role in the invasion of oesophageal carcinoma.

Aged↗

A multicenter validation study of sentinel lymph node biopsy by the Japanese Breast Cancer Society.

Several pilot studies have indicated that SLN biopsy can be used to identify axillary lymph node metastases in patients with breast cancer. To confirm this finding, a multicenter study in a variety of practice settings was performed. A total of 674 patients with breast cancer at five institutions were enrolled. The techniques of SLN identification included the vital dye-guided and the vital dye- and gamma probe-guided methods. The SLN was removed, and complete axillary lymph node dissection (ALND) was performed. SLN and ALND specimens were examined separately. The SLN was successfully identified in 214 (94%) of 227 patients using the combined dye- and gamma probe-guided methods. The SLN was identified in 332 (74%) of 447 patients using vital dye-guided method alone. Patient age of at least 21 years, medially located primary tumor, and clinically positive nodes were correlated with failure to identify the SLN. The accuracy of SLN biopsy for the detection of metastatic disease was 96% (522 of 546), and the sensitivity was 90% (203 of 226). Accuracy of 100% was achieved in the patients with tumors less than 1.6 cm in diameter. All 23 false negative results occurred with larger primary tumors. SLN biopsy can accurately predict the presence or absence of axillary lymph node metastases, particularly in patients with small (< or = 1.5 cm) breast cancers.

Adult↗