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Biomedical subjects

T Iwai

Publications and source records attributed to T Iwai.

At least 145 records · Page 8Linked to original sources
PubMed1997

[Cytogenetic abnormality and prognosis in childhood acute myeloblastic leukemia. Children's Cancer and Leukemia Study Group (CCLSG)].

We report on the leukemic cell karyotype of 180 children with acute myeloblastic leukemia (AML). They were treated by the protocols of chemotherapy for the Children's Cancer and Leukemia Study Group (CCLSG) in the last decade. Of 132 cases with adequate banding analysis, 24.2% had normal karyotype, 21.2% had miscellaneous clonal abnormalities and 54.6% were classified into known cytogenetic subgroups: t(8;21) (n = 35), t(15;17) (n = 23), inv (16) (n = 6), t(11q23;V) (n = 6), -7/7q-(n = 2). Each karyotype was closely correlated with a particular FAB subtype such as t(8;21) in M2, t(15;17) in M3, inv (16) in M4, t(11q23;V) in M5. In the M1+M2 group, although patients with t(8;21) had favorable clinical features such as low WBC counts and less frequent lymphadenopathy, their treatment outcome was not significantly better than those of patients with a normal karyotype (3-year EFS: 58 +/- 11% vs. 47 +/- 12%). Patients with miscellaneous chromosomal abnormalities had a significantly shorter EFS (22% +/- 10%) (p < 0.05) than those with t(8;21) or normal karyotype. In M4+M5 group, 2-year EFS of patients with inv (16) (40 + 30%) was longer than that of patients with normal karyotype (25 +/- 19%), and t(11q23;V) or miscellaneous chromosomal abnormalities (0 +/- 25%). These results suggest that cytogenetic data may be useful for risk-based treatment assignments for children with AML.

Adolescent↗
PubMed1997

[A case of traumatic cardiac contusion accompanied by the rupture of pericardium].

We experienced a case of traumatic cardiac contusion accompanied by the rupture of the pericardium after multiple blunt trauma sustained in a traffic accident. A 26-year-old woman who had suffered from blunt chest and abdominal trauma was admitted to our hospital, being unconscious with multiple severe injuries including pelvic fracture, bilateral hemothorax, and multiple fractures in the extremities. The patient was in a shock status. We performed the transcatheter arterial embolization of the internal iliac arteries to control the bleeding, when aortography showed that the contrast media extravasated toward the left thoracic cavity. Immediately, an operation for blunt chest trauma was performed. Blood was flooding out of the ruptured pericardium because of the contusion of myocardium. The postoperative course was uneventful. Blunt chest trauma is usually accompanied by multisystem injury. Therefore, it is imperative to determine the priority of treatment based on preoperative examination in patients having multiple injuries.

Abdominal Injuries↗
PubMed1997

[Central nervous system metastasis from non-functioning adrenocortical carcinoma: report of a case].

We report a rare case of brain tumor metastasizing from an adrenocortical carcinoma. A 47-year-old man was referred to our department on September 21, 1995, with complaints of episodic loss of consciousness and severe left motor weakness. There was a past history of left adrenalectomy performed in the Department of Surgery of our hospital 9 months before. On admission, computed tomography (CT) and magnetic resonance imaging (MRI) revealed two well circumscribed masses in the right frontal lobe with peritumoral, marked brain edema and metastasis to the lung. The brain tumor was successfully removed via frontal craniotomy 4 days after admission. Histological examination of the tumor specimen revealed metastatic anaplastic cell carcinoma, indicating metastasis from an adrenocortical carcinoma. After chemotherapy with cisplatin, pepleomycin and pirarubicin, he was discharged without neurological deficit. Two months postoperatively, however, the patient received 50 Gy of telecobalt radiation therapy to the whole brain because of recurrence. Three months after-wards, the patient returned complaining of general fatigue. Chest CT scan revealed further enlargement of the lung lesions. Despite repeated chemotherapy, the patient died of lung metastases eight weeks later. Central nervous system metastasis from adrenocortical carcinoma is exceedingly rare. To the best of our knowledge, only 5 cases have been reported. We report here another case of brain metastasis from adrenocortical carcinoma possibly via lung metastasis, and review the pertinent medical literature.

Adrenal Cortex Neoplasms↗
PubMed1996

Myocardial adaptive changes and damage in ischemic heart disease.

Changes in two of the elements of myocardial subcellular organelles relating to cardiac energetics, ventricular myosin isozymes and mitochondrial DNA mutations, were examined using left ventricular tissue samples obtained at autopsy from patients with ischemic heart disease. Myosin isozymes were examined in tissues from nine patients with ischemic heart disease and 12 control patients with cancer but no heart disease. Extracted myosin was separated by pyrophosphate gel electrophoresis. The relative concentration of each component was determined by densitometry. Mitochondrial DNA mutations were evaluated in tissues from ten patients with myocardial infarction and 11 control patients with cancer but no heart disease. DNA was extracted and mitochondrial DNA mutations were detected by the polymerase chain reaction. Two bands were revealed by pyrophosphate gel electrophoresis. These contained VM-A, which exhibited faster electrophoretic mobility and was present in lower concentrations, and VM-B, which had a lower mobility and a higher concentration, respectively. SDS polyacrylamide gel electrophoresis showed that these two components contained the heavy chain and light chains 1 and 2 of myosin. VM-A concentrations tended to be higher in patients with ischemic heart disease than in controls. A 7.4-kb deletion was detected between the D-loop and the ATPase 6 genes of mitochondrial DNA from the myocardium of 6 out of 10 patients with myocardial infarction. The relative amounts of the two myosin isozymes could be altered by ischemic heart disease, although the functional significance of these components is unclear. The changes in the two myosin isozymes might be an adaptive change to disordered energy metabolism, but this change was small. The myocardial mitochondrial DNA deletions in patients with myocardial infarction were thought to result from ischemic damage.

DNA, Mitochondrial↗
PubMed1996

Immunohistochemical detection of Bax and Bcl-2 proteins in gerbil hippocampus following transient forebrain ischemia.

Time-course expression of Bax and Bcl-2 proteins, identified as apoptosis-regulating molecules, was assessed in gerbil hippocampus following transient forebrain ischemia. Brain sections from animals sacrificed at 48, 72, 96 h and 7 days following 5 min ischemia were immunohistochemically evaluated using polyclonal antibodies specific for Bax and Bcl-2 proteins, respectively. The intensity of Bax expression in CA1 neurons increased with time and peaked at 72 h, and immediately disappeared at 96 h following 5 min ischemia. No expression of Bcl-2 in the CA1 neurons was recognized in all the time evaluated.

Animals↗
PubMed1996

A charged segment mainly composed of basic amino acids forms an autoepitope of CENP-A.

Autoantibodies against centromere proteins are commonly found in the serum of patients with scleroderma and other systemic autoimmune diseases. The reactivity of anticentromere autoantibodies (ACA) from 78 patients was investigated by ELISA using two kinds of a 15-amino-acid peptide corresponding to the N- and C-termini of CENP-A, one of the target molecules of ACA. The N-terminal peptide (residues 3-17) was recognized by 85% of ACA, while the C- terminal peptide (residues 126-140) was not. The ELISA result for the N-terminal peptide correlated with the immunoreactivity of CENP-A observed in immunoblotting. Moreover, the binding between autoantibodies and CENP-A was inhibited by the N-terminal peptide in 98.5% of anti-CENP-A- positive sera in immunoblotting. The sequence of peptide, PRRRSRKPEAPRRRS, is highly charged and has two repeats of PRRRS. These results indicate that the N-terminal-charged region forms a major epitope of CENP-A. This area may be involved in the induction of specific autoantibodies against centromere in autoimmune patients.

Amino Acid Sequence↗
PubMed1996

Epitope analysis of chromo antigen and clinical features in a subset of patients with anti-centromere antibodies.

Heterochromatin protein 1 (HP1) is one of the nonhistone chromosomal components tightly associated with the pericentromeric heterochromatic region in Drosophila. The human homologue of HP1 is recognized by a subpopulation of anti-centromere antibodies (ACA). Such autoantibodies recognize a group of several nuclear proteins with Mr of 23-25 kDa and have been termed 'anti-chromo antibodies (AChA)' because an evolutionarily conserved N-terminal half called the 'chromo domain' of HP1 is the epitope. In this study, 84 ACA sera were examined by immunoblotting with recombinant 25-kDa chromo protein (p25). The p25 antigen was expressed as a glutathione S-transferase-fusion protein in E. coli and purified with glutathione-sepharose. Except for one serum specimen, AChA-positive sera reacted with the N-terminus (a.a 16-106) and/or the C-terminus (a.a. 83-191) of p25. Autoimmune response against the N-terminus of p25 in 33 patients was significantly associated with systemic lupus erythematosus and significantly related to leukopenia, thrombocytopenia and elevated erythrocyte sedimentation rate; C-terminal reactivity in 30 patients was significantly associated with primary Sjogren's syndrome and related to leukopenia. The internal 64-amino acid stretch (a.a 43-106) with DNA-binding activity was not autoantigenic. p25 has two separate homologous regions to Drosophila HP1 at the N- and C-termini; the chromo domain and the chromo shadow domain. Patients with autoimmune response against these conserved domains might form a clinical subset of patients positive for ACA.

Animals↗
PubMed1996

Clinical features of anti-chromo antibodies associated with anti-centromere antibodies.

Anti-chromo antibodies (AChA) are autoantibodies accompanying anti-centromere antibodies (ACA). We determined the frequency and clinical significance of AChA in autoimmune rheumatic diseases. Serum samples from 252 patients with rheumatic diseases were examined by immuno-blotting with HeLa nuclear extract and with recombinant N-terminus of 25-kD chromo protein (p25). AChA were detected in 28 (36%) of 77 sera with ACA. AChA were found only in ACA-positive sera. Twenty-two (79%) of 28 recognized a recombinant N-terminal portion of p25, including the chromo domain which is conserved among species. AChA were related to leucopenia, thrombocytopenia, elevated erythrocyte sedimentation rate, and existence of Sjögren's syndrome (SS). In ACA-positive patients, AChA might be a serologic indicator of systemic sclerosis (SSc), having features of systemic lupus erythematosus and/or SS or diseases other than SSc.

Autoantibodies↗
PubMed1996

Effects of FSH on serum immunoreactive inhibin levels in the luteal phase of the menstrual cycle.

OBJECTIVE: FSH causes a dose-related increase in circulating immunoreactive inhibin (INH) in the follicular phase of the menstrual cycle, while LH is the major stimulus to INH secretion by the corpus luteum. The present study was undertaken to assess whether FSH can also stimulate INH production during the luteal phase. DESIGN: Normal volunteers were treated with a single injection of LH-free FSH (Metrodin, 150 units) or saline as control, during the early, mid- or late luteal phase of the cycle, with subsequent hormone measurements. PATIENTS: The 21 volunteers were aged 19-29. Seven subjects given FSH and 8 controls were studied in the early luteal phase, 1-4 days post ovulation. Eight FSH treated subjects and 10 controls were studied in the midluteal phase, 5-9 days post ovulation, and 6 each, respectively, were studied in the late luteal phase. MEASUREMENTS: Oestradiol (E2), progesterone (P), and INH were measured by previously described radio-immunoassays. RESULTS: In both the early and mid-luteal phases, FSH caused a significant rise in INH (early, from 778 to 922 U/l, mid-luteal 1553 to 2090 U/l) and E2 (early 371 to 545 pmol/l, mid-luteal 528 to 636) while there was no significant change in P. No significant changes occurred in the saline treated subjects. In the late luteal phase FSH prevented the significant fall in INH seen in the controls, whilst there was no effect on E2 or P. CONCLUSIONS: It was concluded that both FSH and LH are capable of modulating inhibin production during the luteal phase of the menstrual cycle. FSH may exert its actions on the corpus luteum or alternatively on developing follicles. The present study cannot clearly distinguish between these possibilities.

Adult↗
PubMed1996

Dose-response curve for anaesthetics based on the Monod-Wyman-Changeux model.

We have analysed the dose-response curve for halothane and isoflurane according to the Monod-Wyman-Changeux (MWC) model. This model describes the nature of the physiological data reported by Wakamori, Ikemoto and Akaike for inhibitory Cl currents induced by GABA or glycine in dissociated rat brain neurones and by Herrington and colleagues for Ca2+ currents in clonal pituitary cells. With some assumptions on the difference in response to anaesthetics between patients, the model is applicable in vivo, and it also describes well the human dose-response curve for isoflurane reported by Mather, Raftery and Prys-Roberts. However, the steeply sigmoidal dose-response curve in humans for halothane presented by deJong and Eger is difficult to understand with the same model, because it gives rise to unrealistic MWC variables.

Anesthetics, Inhalation↗
PubMed1996

[Critical limb ischemia].

Chronic critical limb ischemia is defined as ischemia which generally endangers the distal part of a limb. If the ischemia is unrelenting, there is a high risk that amputation will be required. These critical limbs were amputated as an initial treatment long ago. Now it becomes clear that disabling patients have very poor quality of life after major amputation, and ischemic leg produces noxious substances which circulates whole body. So that primary amputation should not be a first choice for the most of the cases. And excellent techniques or new surgical materials bring successful vascular reconstruction to critical limb ischemia. Since we have not a clear definition, European and US criterion seems to be useful for a while. Macrocirculation is represented by ankle systolic pressure and microcirculation by transcutaneous oxygen pressure as well. Its value of les than 10 mmHg means urgent critical condition. Main surgical repairs include below knee bypass using autovein or fine profundaplasty with or without PTA. Usually patients should receive general cares because of high risks.

Angioplasty, Balloon, Coronary↗
PubMed1996

Different response of the rat left and right heart to norepinephrine.

The in vivo hemodynamic and morphologic responses of the rat left (LV) and right (RV) ventricle to continuous long-term i.v. infusion of norepinephrine (NE) at different dosages and for different durations of infusion were studied. Female Sprague-Dawley rats received continuous intravenous infusion of norepinephrine from infors syringe pumps for 24, 48 and 72 h at a dose of 200 mu g center dot kg-1 x h-1. Furthermore, NE was infused for 72 h at dosages of 50, 100 and 200 mu g center dot kg-1 x h-1. The beta-adrenergic blocker and vasodilator with alpha1-blocking activity carvedilol (0.5 mg x kg-1 x h-1) was coinfused with NE for 72 h. The hemodynamic effects were measured on intact, anesthetized rats with special Millar ultraminiature pressure tip catheters, and the weights of the left and right ventricles were measured. NE increased heart rate at any time or dose, whereas cardiac output and total peripheral resistance remained unchanged. LV and RV dP/dtmax were nearly doubled as compared to control values and RVSP was elevated by more than 100%. The effect of NE on LVSP was much less pronounced (< 20%) and only significant at 50 mu g x kg-1 x h-1 for 72 h. Neither LV nor RV end-diastolic pressures were elevated, indicating that cardiac failure had not occurred. The LV developed hypertrophy with an increase of the ventricular weight/body weight ratio (LVW/BW) of 22% even after only 2 days of NE (200 mu g x kg-1 center dot h-1). The RV showed no hypertrophy at any time of the experiments. The NE-induced changes in HR, dP/dtmax, RVSP and LVW/BW were completely prevented by the coinfusion of carvedilol. These studies show that the hemodynamic responses to continuous infusion of NE are more pronounced in the RV than in the LV. Conversely, NE induced hypertrophy only in the LV, not in the RV. The hemodynamic effects of chronic NE infusion did not change significantly between 1 and 3 days of infusion. The in vivo responses to exogenous NE therefore were unaffected by adaptive effects such as downregulation of adrenergic receptors.

Animals↗
PubMed1996

Internal tandem duplication of the flt3 gene found in acute myeloid leukemia.

We analyzed mRNA expression of the flt3 gene in 30 patients with acute myeloid leukemia (AML) and 50 with acute lymphoblastic leukemia (ALL). Using reverse transcriptase-polymerase chain reaction (RT-PCR), expression of flt3 was observed in 61 patients; 22 (73%) with AML and 39 (78%) with ALL. Among these, five patients with AML (one M2, two M4, and two M5) showed unexpected longer transcripts with a primer combination which could amplify the transmembrane (TM) domain through the juxtamembrane (JM) domain. For those patients who expressed flt3 mRNA, the extracellular domain of the flt3 gene was also examined by RT-PCR, but no length abnormality was seen in this region. We further analyzed the TM domain through the second tyrosine kinase domain by genomic amplifications. The five patients who showed aberrant flt3 transcripts exhibited abnormal longer PCR products in addition to the germline products at a region corresponding to the JM through the first TK (TK1) domains. Sequence analyses of the abnormal RT-PCR products demonstrated that partial sequences were tandemly duplicated. Because all these altered transcripts were in-frame, deduced protein products could be expected. Sequence analyses of the genomic DNA revealed that three of the five patients showed a simple internal duplication within exon 11; one had an internal duplication (26 bp) with a 4-bp insertion; and in the fifth patient, a 136-bp sequence from the 3' part of exon 11 to intron 11 and the first 16-bp sequence of exon 12 were each duplicated with 1-bp insertion. In order to confirm the tumor specificity of these alterations, DNA samples obtained at complete remission were also analyzed in the three patients harboring an flt3 duplication, but no abnormal PCR product other than germline was detected in any of the samples. Our results suggest that an internal tandem duplication at the JM/TK1 domains of the flt3 gene is a somatic change detected preferentially in AML, possibly containing a monocytic component.

Acute Disease↗
PubMed1996

An autopsy case of malignant lymphoma with a high serum CA 125 level occurring only in the brain and pericardium.

We report an autopsy case of a central nervous system (CNS) B-cell type lymphoma followed by cardiac tamponade. In this case, lymphoma cells which occurred primarily in the pericardium appear to metastasize to the brain and gradually increase in size in spite of control of the CNS lesion. The serum carbohydrate antigen 125 (CA 125) level was highly elevated and the autopsy findings showed the involvement of lymphoma only in the pericardium rather than the CNS, and the pericardium, not the tumor cells, was immunohistochemically positive for CA 125. Through this rare case, two things are suggested: first, the serum CA 125 level is elevated when B-cell type lymphoma infiltrates the coelomic epithelium; second, CA 125 is overproduced and secreted by the pericardium but not the lymphoma cells. Measurement of the serum CA 125 level may become a diagnostic marker for the infiltration of malignant lymphoma in the coelomic epithelium such as the pericardium, peritoneum or pleura.

Aged↗
PubMed1996

[A case of Dyke-Davidoff-Masson syndrome with total hemiatrophy].

We reported a 39-year-old man with Dyke-Davidoff-Masson syndrome presenting with total hemiatrophy. The patient had a muscle defect in the left occipital lesion at birth and left hemiatrophy including the face in his infancy. The present illness consists of atrophy of the left face, trunk and extremities, a muscle defect accompanied with scleroderma of the left dorsal cervical lesion, bilateral pes cavus, cleft palate, left hemiparesis, including facial palsy and diminished superficial sensation of the left side of the body. Decrease in right cranial volume and slight elevation of the right temporal pyramid and the superior border of the orbit were seen on the X-ray study of the head. Atrophy of the right cerebrum and cerebral peduncle was seen on magnetic resonance imaging. These findings suggest that hemiatrophy of the brain was responsible for total hemiatrophy of the body in this patient. The etiology of cerebral hemiatrophy is not known. There is only a report of Dyke-Davidoff-Masson syndrome accompanied with total hemiatrophy.

Adult↗
PubMed1996

Clinical evaluation of satigrel in intermittent claudicators.

OBJECTIVE: Satigrel is a new antiplatelet agent which was previously shown to inhibit platelet aggregation and have an anti-thrombotic effect in various animal thrombosis models. The present study assessed the effect of oral satigrel on cutaneous circulation in patients with intermittent claudication due to arteriosclerosis obliterans. EXPERIMENTAL DESIGN: Prospective clinical trial with more than 4 weeks follow-up. SETTING: Outpatient department of a university hospital. PATIENTS: Ten patients with intermittent calf claudication were studied (14 limbs with obstruction, 6 limbs without obstruction, and chest wall). INTERVENTIONS: After giving informed consent and one week wash-out of effected agents, a 2 mg oral dose of satigrel twice daily was administered for more than 4 weeks. MEASURES: Transcutaneous partial pressure of oxygen (PtcO2), skin temperature, ankle pressure, and the treadmill test were determined just before therapy, after 2 and 4 weeks of satigrel therapy, and at treatment termination. The paired student's t-test was used for statistical analysis. RESULTS: The PtcO2 in the foot of the ischemic leg showed a significant increase at the end of therapy compared with before therapy (p < 0.05). Skin temperature showed a significant difference in both the ischemic and healthy legs. The walking distance was also significantly extended at therapy termination. CONCLUSIONS: Satigrel improved the cutaneous circulation and symptoms of patients with intermittent claudication.

Adult↗