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Biomedical subjects

T Koizumi

Publications and source records attributed to T Koizumi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Ovarian malignant mixed mesodermal tumor producing the free form of the beta-subunit of human chorionic gonadotropin.

We report a patient with ovarian malignant mixed mesodermal tumor (MMMT) that produced immunoreactive human chorionic gonadotropin beta-subunit (IR-hCG beta). Qualitative analysis indicated that IR-hCG beta in the patient's serum represented the free form of the beta-subunit of hCG. Immunohistochemical localization of hCG beta in MMMT was observed in the sarcomatous stroma, but not in the adenocarcinoma component. Reverse transcription-polymerase chain reaction (RT-PCR) for hCG subunits revealed that the mRNA transcripts of two of six hCG beta genes (beta-1 and -2) were predominantly expressed in the tumor tissue. The serum level of free hCG beta correlated with disease status and was helpful for monitoring the response to therapy for MMMT in this patient.

Adenocarcinoma↗
PubMed2001

Phase I trial of weekly docetaxel combined with cisplatin in patients with non-small cell lung cancer.

The phase I study was conducted to evaluate the maximum tolerated dose (MTD) and toxicity of weekly administered docetaxel combined with cisplatin in patients with non-small-cell lung cancer (NSCLC). In a dose escalation study, 22 patients, under 75 years old, with unresectable and metastatic untreated NSCLC with performance status (0-1) were enrolled. Patients were treated with cisplatin (day 1) and weekly docetaxel (days 1, 8, 15). Dose escalation levels in mg/m(2) were for cisplatin and docetaxel; 70 and 15 (level 1), 80 and 15 (level 2), 80 and 20 (level 3), 80 and 25 (level 4), 80 and 30 (level 5), respectively. Chemotherapy was repeated for at least two cycles every 28 days. All patients were assessable for toxicities. Although grade 3 neutropenia occurred in one case in level 4, there were no significant modifications of chemotherapy schedule until level 4. Grade 3 neutropenia occurred in all cases receiving level 5. One patient developed an infection, and two had incomplete recovery of neutropenia by the 28th day after the first cycle of chemotherapy. Nonhematological toxicities, including nephrotoxicity, nausea/vomiting, alopecia and hypersensitivity reaction, were tolerable. However, one case developed severe hyponatremia. Among 21 patients evaluable for response, eight cases achieved partial response, thus the overall response was 39%. Weekly administration of docetaxel at 25 mg/m(2) (days 1, 8, 15) combined with cisplatin 80 mg/m(2) (day 1) is recommended for phase II studies. The responses observed in the present study suggest an identical high degree of activity against NSCLC with less hematotoxicity compared with a standard schedule of cisplatin and docetaxel.

Adult↗
PubMed2001

Kinetic analysis of cytokine gene expression in patients with GVHD after donor lymphocyte infusion.

Patients who receive a donor lymphocyte infusion (DLI) for the treatment of relapsed leukemia after allogeneic BMT (alloBMT) often developed GVHD. To determine whether cytokines might have a role in GVHD, an intensive kinetic analysis of in vivo cytokine gene expression was performed on PBMC from three such patients. Expression of IL-1beta, IL-2, IFN-gamma, IL-4, IL-5, IL-8, IL-10, IL-12, TNF-alpha, and IL-2Ralpha was examined using a sensitive semi-quantitative reverse transcription (RT)-PCR assay system. Six normal controls were also analyzed for comparison. Expression of type 1 T helper (Th1) cytokines, IL-2 and IFN-gamma was greatly increased in all three patients. In particular, the changes in IL-2 gene expression correlated well with disease progression, suggesting that IL-2 has a critical role in the development of GVHD. Although the pattern of type 2 T helper (Th2) cytokine gene expression differed in each patient, the expression of IL-4 was inversely related to expression of Th1 cytokines. These results suggest that Th1 dominates in the development of human clinical GVHD.

Adult↗
PubMed2001

Screening of ischemic heart disease with cavernous artery blood flow in erectile dysfunctional patients.

Erection is a hemodynamic event and accordingly, erectile dysfunction (ED) is closely related with ischemic heart disease. We should confirm that the cardiac condition of the ED patient is safe enough to perform sexual intercourse prior to beginning treatment for ED. Asymptomatic ischemic heart disease cannot be diagnosed only in an interview, but it's difficult to perform cardiac exercise tests on all patients complaining of ED. Therefore, screening methods to evaluate patients who should undergo exercise tests are needed. Sixty patients with erectile dysfunction participated in this study. Physical examinations, interviews, and color Doppler examinations were conducted. Chest X-rays and electrocardiograms of all patients in the resting position were obtained, as were electrocardiograms following exercise. Echocardiograms, treadmill test results, thallium exercise scintigrams, and coronary angiograms were obtained as required for diagnosis. Two patients were excluded because they had obvious arteriogenic ED due to perineal injury. Fifty-eight patients underwent Doppler evaluations of their cavernous arteries and heart exercise tests. Fourteen patients (24.1%) were diagnosed with ischemic heart disease. Although six of them had already been diagnosed with ischemic heart disease, eight were newly diagnosed by the exercise tests. Cardiovascular risk factors such as advanced age, hyperlipidemia, diabetes mellitus, hypertension, smoking, and obesity were not sufficient predictive factors. The mean peak systolic velocity of the patients without ischemic heart disease was 34.6 cm/s vs 22.0 cm/s in those with ischemic heart disease. Only 3.7% of patients whose peak systolic velocity in the cavernous artery was equal to or exceeded 35 cm/s had ischemic heart disease. On the other hand, 41.9% of patients with peak systolic velocity of less than 35 cm/s had ischemic heart disease. The sensitivity of peak systolic velocity against ischemic heart disease was 92.9%, and specificity was 59.1%. In ED patients, incidences of complications involving symptomatic or asymptomatic ischemic heart disease were found to be high. The peak systolic velocity in the cavernous artery is thought to be a useful predictive factor of ischemic heart disease in ED patients. When a patient reveals a peak systolic velocity of less than 35 cm/s, he should undergo heart exercise tests prior to treatment of ED.

Adult↗
PubMed2001

Partial monosomy 10q with partial trisomy 11q due to paternal balanced translocation.

A male neonate with partial monosomy 10q and partial trisomy 11q, due to paternal balanced translocation, and who had cerebellar and olfactory lobe hypoplasia, cardiovascular defects, duodenal atresia and imperforate anus, is presented. To the best of our knowledge, this is the first report on this combination of chromosomal abnormalities.

Abnormalities, Multiple↗
PubMed2001

Epidemiology of suicidal ideation and help-seeking behaviors among the elderly in Japan.

This study offers an analysis of the elderly (over 65 years of age) among a general community population in terms of the percentages of: (i) persons with recurring thoughts of death and/or of committing suicide, and (ii) people who have consulted others, including medical professionals, with regard to these problems. Among 433 elderly over the age of 65 in one community in a town in Aomori Prefecture, 358 agreed to participate in the project. Forty-four participants (12.3%) responded that they had either 'thoughts of death' or 'thoughts of suicide', and these thoughts had continued for more than 2 weeks in 12 participants (3.4%). Only 15 of the 44 suicidal elderly responded that they had consulted someone about their problems. Although there are many elderly people exhibiting a subclinical depressive state with recurring thoughts of death or thoughts of suicide, the number of people who consult family members, professionals, or others is very low. This suggests the importance of community networking through educational activities so that people can more readily talk to and support one another.

Aged↗
PubMed2001

Two cases of bronchial asthma after treatment with amiodarone.

Amiodarone is a highly effective antiarrhythmic agent for the prevention of life-threatening arrhythmias. Two cases are described of patients who developed bronchial asthma after treatment with amiodarone. The bronchial asthma resolved after the dose of amiodarone was decreased in both patients. To our knowledge, an association between amiodarone and severe bronchial asthma has previously been reported only once in the medical literature. Physicians should note that amiodarone may cause bronchospasm in susceptible patients.

Aged↗
PubMed2001

Pathological features of the lung in fatal high altitude pulmonary edema occurring at moderate altitude in Japan.

In order to characterize the pathological features of high altitude pulmonary edema (HAPE) occurring at moderate altitude in Japan, we performed routine hematoxylin and eosin (HE) staining in lung materials from HAPE autopsied cases. We also undertook advanced immunohistochemical staining for observation of type II pneumocytes, pulmonary surfactant (PS), and mast cells in the lung of HAPE cases to examine the biological changes within the lung parenchyma. The pathological findings of HAPE were characterized by alveolar edema, congestion of pulmonary vessels, alveolar hyaline membranes, alveolar hemorrhage, and multithrombi and fibrin clots, but maintained alveolar structure. The immunostaining results showed that the type II pneumocytes were cellular fusion, deformity, and exfoliation from the walls of alveoli; the PS not only lined the alveolar surface, but was also patchily distributed within alveoli; and the number of mast cells were increased (9.0 +/- 0.9 cells/mm(2)) compared to that in controls (1.1 +/- 0.4 cells/mm(2)) (p < 0.01). We conclude that the pathological features of HAPE at moderate altitude in Japan are similar to others reported worldwide, and that the type II pneumocytes, PS, and mast cells may contribute to some extent to pathophysiological parts in the development and progression of HAPE.

Adolescent↗
PubMed2001

Immunohistochemical expression of gastric mucin and p53 in minimal deviation adenocarcinoma of the uterine cervix.

Comparative immunostaining with antibodies against gastric mucin and p53 was performed on 6 cases of minimal deviation adenocarcinoma (MDA) of the uterine cervix. The MDAs consisted of predominant areas of glands lined by extremely well-differentiated tall columnar epithelial cells with little cytological atypia and minor foci of less well-differentiated glandular epithelium with a minor degree of nuclear atypia. Immunostaining for gastric mucin with a monoclonal antibody HIK1083 revealed that all the tumors areas of typical MDA were partly immunoreactive for HIK1083, but the coexisting less well-differentiated glands were essentially negative. Four MDAs focally contained cells with p53 positive nuclei that were located exclusively in the less well-differentiated cells that lacked gastric mucin. In the pelvic lymph nodes in 2 cases, most of the metastatic tumor was less differentiated and a positive reaction for HIK1083 was observed only in small foci of typical MDA. No significant overexpression of p53 was observed in the metastases. Immunohistochemical expression of gastric mucin and p53 may be related to the histological differentiation of MDA, and detection of p53 overexpression may help to identify critical steps in the local progression of MDA.

Adenocarcinoma↗
PubMed2001

Matrix metalloproteinase-2 in dentin matrix mineralization.

In the serum-free culture medium of bovine odontoblasts we detected active gelatinolytic metalloproteinases, matrix metalloproteinase (MMP)-2 and MMP-9 (gelatinases A and B). The activity of MMP-2, in particular, appeared suddenly around day 21 in the culture, coinciding with the development of odontoblastic cell processes and the loss of alkaline phosphatase. Reverse transcriptase-polymerase chain reaction analysis of these odontoblasts demonstrated that messages of MMP-2 but not MMP-9 increased significantly between day 15 and day 21. The in vitro observation indicates that medium conditioned by these odontoblasts and containing significant amounts of MMP-2 degrades not only the collagenous substrates but also purified dentin phosphophoryn as well. We have also observed that dephosphorylated dentin phosphoprotein becomes a better substrate for casein kinase II after limited proteolysis with MMP-2. These results support our working hypothesis that MMP-2-mediated proteolytic processing is an important step in accelerating the process of dentin matrix maturation, which includes phosphorylation and subsequent mineralization. As has been suggested previously, extracellular phosphorylation of matrix proteins is an important step in biomineralization both in bone and in dentin (Mikuni-Takagaki et al., J Bone Miner Res 1995;10:231-42; Zhu et al., Biochem J 1997; 323:637-43). Our present histochemical analysis in MMP-2 knockout mice confirms the concept with the delayed formation of mineralized tissues, dentin, and bone.

Alkaline Phosphatase↗
PubMed2001

Serial pentamidine levels in bronchial epithelial lining fluid after aerosol administration.

BACKGROUND: There is no information on serial pharmacokinetic assessment in the lungs after administration of aerosolized pentamidine. OBJECTIVE: The present study was performed to evaluate the elimination of aerosolized pentamidine from bronchial airways following inhalation. METHODS: We used 4 sheep with tracheotomies in the present study. Pentamidine (300 mg) was administered by inhalation to each animal. Serial bronchial washing to obtain epithelial lining fluid (ELF) was performed 1, 7, 10, 14, 21 and 28 days after administration of aerosolized pentamidine in each animal. The pentamidine concentration in the supernatant of ELF was measured by high-performance liquid chromatography. RESULTS: The maximal pentamidine level on the first day (12 h after inhalation) was 616.5 +/- 238.2 ng/ml (mean +/- SE) in ELF. The pentamidine levels rapidly decreased within 2 weeks (8.9 +/- 1.2 ng/ml at 14 days), followed by slow elimination (8.9 +/- 0.8 ng/ml at 28 days). Thus, inhaled pentamidine showed a rapid clearance from the bronchial wall within the first 2 weeks. CONCLUSIONS: These findings may be useful in designing and interpreting future studies of aerosolized pentamidine in patients who are receiving inhaled pentamidine, especially for those with failure of prophylaxis for Pneumocystis carinii pneumonia.

Administration, Inhalation↗
PubMed2001

Clearance of filtered fluid from the lung during exercise: role of hyperpnea.

During strenuous exercise in sheep, lung lymph flow increases within seconds and rises to levels 7- to 10-fold over baseline. Concomitant with the flow increase, the lymph protein content rapidly decreases to levels consistent with severe capillary hypertension. This pattern of clearance of filtered fluid is quite different than is seen with the passive capillary hypertension that results from mechanical obstruction of the mitral valve. In passive capillary hypertension, the increase in lymph flow and reduction in lymph protein content develop over several hours. The purpose of this study was to discover if these observed differences in edema clearance are related to the hyperpnea that accompanies exercise. Sheep were instrumented for continuous measurement of pulmonary arterial, left atrial, and systemic pressures, cardiac output by ultrasound, lung lymph flow, and ventilation. First, hemodynamics, ventilatory, and lymph clearance variables were measured during moderate exercise at 2.8 mph on a treadmill. Second, on a separate occasion, sheep were induced to hyperventilate to the same minute ventilation as during exercise, using modest CO2 stimulation. Lymph flow and hemodynamics were unaffected by this hyperpnea. The third arm of the experiment was to raise pulmonary microvascular pressure at rest to the level seen with exercise by means of a balloon catheter placed in the mitral valve. Lymph flow rose and protein content decreased slowly and to a lower degree than seen with exercise despite a comparable microvascular pressure. Finally, left atrial hypertension and induced hyperpnea were combined in sheep at rest, and the resulting lymph flow and protein content were the same as seen with exercise at similar pressures and ventilation. We conclude that hyperpnea is a major mechanism of interstitial liquid clearance during exercise, and may be largely responsible for preventing pulmonary edema that might occur at the high microvascular pressures of strenuous exercise.

Animals↗
PubMed2001

Hypersensitivity pneumonitis induced by spores of Lyophyllum aggregatum.

OBJECTIVES: Lyophyllum aggregatum (LA) is called Shimeji in Japanese and is eaten commonly as a mushroom. Shimeji mushrooms are cultivated in an indoor environment all year round. This study aimed to clarify the clinical features of hypersensitivity pneumonitis (HP) induced by LA. PATIENTS AND SETTING: Ten patients showed mild respiratory symptoms including dry cough, sputum, and low-grade fever. We tried to characterize the clinical features and the findings using chest high-resolution CT (HRCT), pulmonary function tests (PFTs), and BAL fluid (BALF) tests in patients with HP induced by LA. HP was diagnosed from clinical features, HRCT findings, BALF findings, lung histology, and lymphocyte stimulation tests (LSTs) for LA. RESULTS: Laboratory findings showed mean (+/- SD) elevated levels of C-reactive protein (0.78 +/- 1.3 mg/dL), erythrocyte sedimentation rate (48 +/- 23 mm/h), and gamma-globulin (26.9 +/- 7.6%). PFTs revealed a slight decrease in the percentage diffusing capacity of the lung for carbon monoxide, possibly due to the presence of epithelial granulomas in the alveoli. Although 4 of 10 patients showed normal findings on the chest radiograph (CXR), chest HRCT findings of all patients showed centrilobular small nodules and diffuse ground-glass opacities. The BALF testing revealed an increase in total cell counts, showing predominantly activated T lymphocytes. The CD4/CD8 cell ratio was significantly decreased (0.5 +/- 0.3). The results of the LSTs were positive in seven of seven cases. CONCLUSIONS: Since patients with HP induced by LA typically have mild respiratory symptoms and sometimes normal CXR findings, their conditions might remain undiagnosed. However, the chest HRCT images showed the typical subacute phase of HP.

Adult↗
PubMed2001

Superior mesenteric artery blood flow velocity in small for gestational age infants of very low birth weight during the early neonatal period.

In order to elucidate intestinal blood flow after birth in infants with intrauterine growth retardation, we measured superior mesenteric artery blood flow velocity in uncomplicated small for gestational age infants with a birth weight of < 1500 g by pulsed Doppler ultrasound in days 1 to 7 of life. Peak systolic blood flow velocity, time-averaged mean blood flow velocity and end-diastolic blood flow velocity in the superior mesenteric artery significantly increased with time. The resistance index and relative vascular resistance in the superior mesenteric artery significantly decreased after birth. Compared with gestational age matched appropriate for gestational age infants and birth weight matched appropriate for gestational age ones, peak systolic blood flow velocity, time-averaged mean blood flow velocity and end-diastolic blood flow velocity in the superior mesenteric artery were lower in the small for gestational age infants. The difference between the small for gestational age group and the gestational age matched appropriate for gestational age group was statistically significant. The resistance index and relative vascular resistance in the superior mesenteric artery tend to be higher in the small for gestational age group than in the appropriate for gestational age groups. In conclusion, although intestinal blood flow velocity in infants with intrauterine growth retardation increases after birth, it is lower than appropriate for gestational age infants during the early neonatal period.

Aging↗
PubMed2001

Atrial natriuretic peptide and red cell 2,3-diphosphoglycerate in patients with chronic mountain sickness.

BACKGROUND: Individuals with chronic mountain sickness (CMS) show severe hypoxemia, excessive polycythemia, and marked pulmonary hypertension. The pathophysiologic mechanisms of CMS are still not completely understood. METHODS: We determined plasma atrial natriuretic peptide (ANP), red cell 2,3-diphosphoglycerate (2,3-DPG), hematocrit, hemoglobin, and arterialized ear lobe blood gas values in 13 patients with CMS (9 Hans, 4 Tibetans) and 18 control Han Chinese men of similar age, height, and weight who had been living at 4300 m on the Tibetan plateau of Qinghai Province, China, for approximately 14 years. RESULTS: A significantly higher level of ANP was found in the CMS patients compared to the non-CMS patients (113.4+/-5.5 pg/mL vs 87.6+/-4.7 pg/mL, P < .01), and the levels of ANP correlated positively with the hemoglobin concentration (r = 0.8282, P < .01). The 2,3-DPG levels in the CMS patients were significantly increased compared to the non-CMS subjects (5.23+/-0.16 mmol/L vs 4.40+/-0.12 mmol/L, P < .01), and the 2,3-DPG concentrations in the CMS patients were negatively correlated with their PaO2 values (r = -0.7898, P < .01). The CMS patients had significantly higher PaCO2 levels, lower pH values, lower PaO2 levels, and greater alveolar-arterial oxygen differences (PAO2 - PaO2) compared to the non-CMS subjects. CONCLUSIONS: These findings suggest that overproduction of ANP and 2,3-DPG at high altitudes may play an important role in the pathophysiology of chronic mountain sickness.

2,3-Diphosphoglycerate↗