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Biomedical subjects

K Kitamura

Publications and source records attributed to K Kitamura.

At least 685 records · Page 38Linked to original sources
PubMed1993

[Clinical study of GM-CSF in patients with aplastic anemia and myelodysplastic syndrome. (CSF39-300 Study Group)].

We administered granulocyte-macrophage colony stimulating factor (GM-CSF) to patients with aplastic anemia and myelodysplastic syndrome (MDS), as a phase III trial. The GM-CSF was given by 3 hrs intravenous drip infusion daily for at least fourteen days. Twenty-five patients with aplastic anemia and nineteen patients with MDS were evaluable for efficacy. Peripheral blood granulocyte counts, especially neutrophil counts and eosinophil counts, increased markedly by the administration of GM-CSF in each disease. Fifteen patients with MDS and nineteen patients with aplastic anemia responded to the GM-CSF. Dose-related increase of granulocytes were seen in patients with MDS, but no relation was seen in patients with aplastic anemia. Adverse effects were observed in some patients and flu-like syndrome including fever, general fatigue and anorexia were seen most commonly but were transient. Our results showed that GM-CSF is a potent stimulator of hematopoiesis in patients with aplastic anemia and MDS.

Adolescent↗
PubMed1993

[Clinical evaluation of S-1108 in children].

We administered S-1108 to 16 children with ages ranging from 7 month to 15 years at doses between 1.8 and 6.0 mg/kg x 3/day for 3 to 13 days. We evaluated the efficacy and safety of S-1108 in 11 children with respiratory tract infections, 3 urinary tract infections, and 2 skin infections. The efficacy rate of S-1108 was 100% and bacteriological eradication rate was 83.3%. No adverse effects were observed. These results suggested that S-1108 could be used safely in children.

Adolescent↗
PubMed1993

Long-term results of esophagectomy for early esophageal carcinoma.

In this paper we report on the long-term results achieved in 75 patients with superficial carcinoma of the thoracic esophagus who have been treated since 1965 with esophagectomy at our institute. In three of these patients, the carcinoma was limited to the epithelium (intra-epithelial carcinoma), while in 13 cases it was confined to the mucosa, and in 59 cases to the submucosa. There was no lymph node metastasis in patients with intra-epithelial or mucosal carcinoma, but lymph node involvement was found in 13 (22.0%) of the 59 cases of submucosal carcinoma. The five-year survival rate of patients with intra-epithelial carcinoma and mucosal carcinoma was 100%, which was significantly better than that for carcinoma invading the submucosa (49%). The five-year survival rate for patients with lymph node involvement was only 46%, which was significantly worse than that for patients without lymph node involvement (60%). No recurrence occurred in patients with intra-epithelial carcinoma or mucosal carcinoma, while recurrent disease occurred in 19 (32.2%) of the 59 patients with submucosal carcinoma. Lymph node recurrence and hematogenic recurrence such as lung and bone metastasis were the most frequent developments in patients with submucosal carcinoma of the esophagus.

Adult↗
PubMed1993

How to detect early carcinoma of the esophagus.

In order to identify the most effective approaches for detecting early carcinoma of the esophagus, 46 patients with such lesions, including three epithelial, 13 mucosal and 30 submucosal carcinomas, were studied. Among 16 patients with epithelial and mucosal carcinomas, five (31%) were symptomatic, and in 15 (94%), the lesions were detected by endoscopy. Among 30 submucosal carcinomas, 17 (57%) were associated with symptoms such as mild dysphagia and a sharp pain, and 22 (73%) were detected by endoscopy. With respect to the gross appearance of early esophageal carcinoma, a protruded type frequently caused symptoms (70%) and was often detected by radiology (50%). Although endoscopy always permitted a correct diagnosis of the lesion (100%), radiology often failed to detect it (47%), especially when the lesion was of the superficial type. In asymptomatic patients, most early esophageal carcinomas were detected during the follow-up of gastric diseases, mass-screening or medical examination for gastric cancer, and in connection with abdominal pain due to other diseases. These results indicate that, in order to detect early carcinoma of the esophagus, it is important to perform Lugol-combined endoscopy with biopsy rather than radiology.

Adult↗
PubMed1993

Carcinomatous invasion and lymphocyte infiltration in early esophageal carcinoma with special regard to the basement membrane. An immunohistochemical study.

We examined 24 cases of superficial esophageal carcinoma and evaluated 94 areas, including 43 intra-epithelial (ep), 36 mucosal (m) and 15 submucosal (sm) areas, using the immunohistochemical staining of laminin to detect the basement membrane. The staining pattern was divisible into three patterns, i.e., continuous, fragmentary and defective. Defective patterns were observed in 14%, 53%, and 73% of the ep, m, and sm lesions, respectively (p < 0.01). With regard to the degree of lymphocyte infiltration, 77% of the continuous areas were accompanied by a low lymphocyte infiltration, while 56% of the defective areas were accompanied by dense infiltrations with follicle formation. Lymphocyte infiltration was thus statistically significantly (p < 0.01) more closely associated with the defective areas than with the continuous areas. Furthermore, urokinase-type plasminogen activator was detected immunohistochemically in 11.1% of the defective areas, and in none of the continuous areas. These findings suggested 1) that superficial esophageal carcinoma might progress while destroying the basement membrane, and 2) that as host immune reactions lymphocytes might infiltrate the lesions where the basement membranes were destroyed and cancer cells exposed to the underlying layer. The findings also suggested the possibility that the degradation of the basement membrane might be caused by proteolytic enzymes produced by cancer cells.

Adult↗
PubMed1993

DNA ploidy as a prognostic factor in early esophageal carcinoma.

Cell nuclear DNA content was cytophotometrically determined in biopsy specimens obtained from thirty-five patients with superficial esophageal carcinoma. The relationship between the DNA distribution pattern and histopathological features, prognosis and postoperative survival time was then investigated. Patients with a low ploidy pattern had a more favorable postoperative course, with 62% attaining a 5-year survival rate, than those with high ploidy, of whom 34% attained a 5-year survival rate (p < 0.01). The recurrence rate was higher for the high ploidy pattern (64.3%) than for the low ploidy pattern (35.3%). Moreover, the rate of recurrence within 2 years was 50% in high ploidy, which was higher than the 5.9% rate in the case of low ploidy (p < 0.05). Although there was no clearly established relationship between the DNA distribution pattern and clinicopathological features, a multivariate analysis revealed that the DNA distribution pattern was one of the independent and significant prognostic factors of superficial esophageal carcinoma. These results thus suggest the usefulness of a preoperative DNA analysis of biopsy specimens in predicting the prognosis and determining perioperative therapeutic strategy for both superficial esophageal carcinoma and for advanced cases.

Adult↗
PubMed1993

The evaluation of submucosal carcinoma of the esophagus as a more advanced carcinoma.

Of 75 patients with superficial esophageal carcinoma, there were 16 cases with epithelial or mucosal, and 59 cases with submucosal, lesions. The incidence of nodal metastasis in patients with epithelial or mucosal carcinoma was zero, and the 5-year survival rate was 100%. However, 13 out of 59 cases (22.0%) with submucosal carcinoma were accompanied by nodal involvement, and the rate of vessel invasion was 27.1% (16/59). Even in 46 cases of submucosal carcinoma without nodal involvement, there were 13 cases (22.1%) with vessel invasion. The 5-year survival rate of the 26 submucosal cases with either nodal metastasis or vessel invasion was 37.6%, and even that of the 33 cases with neither lymph node metastasis nor vessel invasion was 60.0%. On the other hand, of the 74 patients with carcinoma invading the muscularis propria, there were 35 cases (47.3%) without nodal metastasis and 27 cases (36.5%) which were also free of vessel invasion. The 5-year survival rate of the former was 32.6%, and of the latter 33.1%. On the basis of these findings, we wish to emphasize that submucosal carcinoma should be classified as an advanced carcinoma.

Adult↗
PubMed1993

Mediastinal drainage prevents fatal pyothorax from anastomotic leakage after intrathoracic anastomosis in reconstruction for carcinoma of the esophagus.

In our experience, anastomotic leakage occurred in five of 69 patients with intrathoracic anastomosis after resection of carcinoma of the esophagus. In the early period, only an ordinary right thoracic drain was put in place, and when leakage occurred, two patients died because of pyothorax, while one patient was saved by surgical drainage. However, in the recent period, in addition to the ordinary right thoracic drain, another drain has also been placed just distal to the anastomosis through the esophageal hiatus through the abdominal cavity, exiting the abdominal wall. After such procedure, drainage has been adequate without any occurrence of pyothorax, even when anastomotic leakage occurred, as in the two most recent instances. Therefore, unless drainage is inadequate and surgical drainage is indicated, as in instances of necrosis of substitutes, mediastinoabdominal drainage seems to be effective in the treatment of intrathoracic anastomotic leakage.

Aged↗
PubMed1993

[Clinical application of new cytokines].

Recent progress of molecular biology and gene technology has developed a novel approach of clinical treatment. Several recombinant cytokines are already applied to clinical field. In this symposium, I introduced clinical application of some cytokines including GM-CSF, interleukin (IL)-1 and IL-3. The clinical benefits of IL-1 are; 1) IL-1 has an anti-tumor effect especially on cutaneous lymphoma and brain tumors, and 2) IL-1 has a function as hematopoietic growth factor for very immature hematopoietic stem cells. In the clinical Phase I/II study, IL-1 has been shown to have anti-tumor effect on cutaneous T-lymphoma via immune mechanisms. The side effects of IL-1 were variable including fever, fatigue, skin redness and so on, but they were all tolerable. The clinical phase studies of GM-CSF and IL-3 are now on going. The preliminary studies show that GM-CSF has granulo-poietic activity but not thrombo-poietic activity, and that IL-3 has multi-hematopoietic activity. These cytokines may be useful for treatment of disorders of hematopoietic stem cells such as aplastic anemia and myelodysplastic syndrome. The side effects of both cytokines are resemble, but all are tolerable.

Anemia, Aplastic↗
PubMed1993

Secondary early carcinoma in a reconstructed gastric tube after subtotal esophagectomy for early carcinoma of the esophagus.

A 70-year-old man was found to have a moderately differentiated squamous cell carcinoma in the mid-esophagus on X-ray and endoscopy. These examinations revealed no lesion in the stomach at that time. Ten days after termination of preoperative hyperthermo-chemo-radiotherapy (HCR), a subtotal esophagectomy and gastric tube reconstruction via the retrosternal route were performed (pTNM stage I). Seven months later, another early cancer was detected in the reconstructed gastric tube. Via a median sternotomy, a wedge resection of the gastric tube was performed, and histopathological studies revealed a well-differentiated adenocarcinoma, which was limited to the submucosa (pTNM stage I). The patient has since done well with no signs of recurrence for the twenty-two months that have elapsed since the second operation was performed. Since the incidence of double cancer in the esophagus and stomach is high, and cases such as that described here will be detected more and more frequently in the future, not only a thorough investigation of a stomach intended for use in the reconstruction of the esophagus, but also strict postoperative checkups of the gastric tube when the esophagus has been reconstructed using the stomach must be considered of great importance.

Adenocarcinoma↗
PubMed1993

Acute electrolyte disturbances in coronary sinus during left coronary arteriography in man.

Electrolyte disturbances, particularly reduction of ionized calcium, induced by iodinated contrast media (CM) are important considerations in coronary arteriography. A study was conducted in 24 patients to evaluate the acute electrolyte alterations in the coronary sinus during left coronary arteriography. During left coronary arteriography, coronary sinus blood was withdrawn for measurement of electrolytes. The CM used were diatrizoate, ioxaglate, iohexol, and iopamidol. The hematocrit was decreased moderately by all 4 CM used at 5 s and returned to the control level at 15 s. The level of ionized calcium was decreased by all CM at 5 s. Prolonged reduction of ionic calcium was observed with diatrizoate and ioxaglate at 15 s. The level of potassium was almost unchanged by diatrizoate and ioxaglate in spite of hemodilution, which may lead us to a hypothesis that potassium can be released from the intracellular spaces such as red blood cells and vascular endothelial cells. Thus the depression of left ventricular function might be caused not only by reduction of ionized calcium, but also by a relative increase in the level of serum potassium.

Adult↗
PubMed1993

[A case report of mediastinal teratoma complicated with cardiac tamponade].

A 10-year-old Japanese boy was admitted to our hospital with complaints of the sudden and severe chest pain having occurred when he caught a ball on his chest. A chest X-ray film and MRI made a diagnosis of cardiac tamponade caused by perforation into the pericardial sac of a mediastinal teratoma and pericardial drainage was carried out. Pericardial effusion showed cloudy yellow and CA 19-9 level in the effusion was 6, 538.2 U/ml. The tumor was extirpated after recovery of his general condition. The tumor was consisted of solid material (5 x 6 x 3 cm) and of cystic part (4 x 6 x 0.8 cm) involving of viscous yellowish fluid. Microscopic sections showed ulcer with bleeding, granulation and pancreatic tissue. Histopathological diagnosis was benign mature teratoma. Including this case, fourteen cases of mediastinal teratomas with cardiac tamponade have been reported and this is the youngest case. Pancreatic tissue were observed histopathologically in most cases and it was thought that autodigestion by digestive enzyme from pancreas was major cause of perforation of the tumor into the pericardial sac.

Cardiac Tamponade↗
PubMed1992

Local administration of monoclonal antibody-drug conjugate: a new strategy to reduce the local recurrence of colorectal cancer.

This report investigates the application of monoclonal antibody A7 and its drug conjugate in locally controlling colorectal cancer. The experimental protocol consisted of local retention, lymphatic delivery, normal organ distribution, systemic toxicity, and tumoricidal effects. When 125I-labeled monoclonal antibody (Mab) A7 was injected into the pelvis and the thigh of Balb/c mice, a high local retention unrelated to antigen-antibody interaction was observed at the injected site for 24 h after injection. An analysis of local retension properties related to antigen-antibody interaction, conducted by intratumorally or peritumorally injecting 125I-Mab A7 into the tumor-bearing athymic nude mice, revealed a significantly higher tumor localization of Mab A7 in comparison to i.v. injection. 125I-Mab A7 accumulated to a great extent in the ipsilateral regional lymph node but not in the contralateral regional lymph node. Normal organ accumulation of Mab A7 was lower in the locally injected group than in the i.v. injected group. Intratumoral injection of Mab A7-neocarzinostatin (A7-NCS) led to the complete remission of established tumor in 5 of 6 antigen-positive xenograft-bearing mice but exhibited a complete remission in only 1 of 6 antigen-negative xenograft-bearing mice. A single local injection of A7-NCS inhibited tumor development in 12 of 16 and 5 of 15 antigen-positive tumor-bearing mice and antigen-negative tumor-bearing mice, respectively, whereas neither a systemic injection of A7-NCS and NCS nor a local injection of NCS and saline had a notable inhibitory effect on tumor development. Systemic toxicity of NCS was markedly reduced when it was locally administered in the antibody-conjugated form. These findings indicate that local injection of immunoconjugate is a promising new field for controlling the local recurrence of colorectal cancer.

Animals↗
PubMed1992

Crystal structure of papain-E64-c complex. Binding diversity of E64-c to papain S2 and S3 subsites.

In order to investigate the binding mode of E64-c (a synthetic cysteine proteinase inhibitor) to papain at the atomic level, the crystal structure of the complex was analysed by X-ray diffraction at 1.9 A (1 A is expressed in SI units as 0.1 nm) resolution. The crystal has a space group P2(1)2(1)2(1) with a = 43.37, b = 102.34 and c = 49.95 A. A total of 21,135 observed reflections were collected from the same crystal, and 14811 unique reflections of up to 1.9 A resolution [Fo > 3 sigma(Fo)] were used for the structure solution and refinement. The papain structure was determined by means of the molecular replacement method, and then the inhibitor was observed on a (2 magnitude of Fo-magnitude of Fc) difference Fourier map. The complex structure was finally refined to R = 19.4% including 207 solvent molecules. Although this complex crystal (Form II) was polymorphous as compared with the previously analysed one (Form I), the binding modes of leucine and isoamylamide moieties of E64-c were significantly different from each other. By the calculation of accessible surface area for each complex atom, these two different binding modes were both shown to be tight enough to prevent the access of solvent molecules to the papain active site. With respect to the E64-c-papain binding mode, molecular-dynamics simulations proposed two kinds of stationary states which were derived from the crystal structures of Forms I and II. One of these, which corresponds to the binding mode simulated from Form I, was essentially the same as that observed in the crystal structure, and the other was somewhat different from the crystal structure of Form II, especially with respect to the binding of the isoamylamide moiety with the papain S subsites. The substrate specificity for the papain active site is discussed on the basis of the present results.

Amino Acid Sequence↗