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Biomedical subjects

M Kitajima

Publications and source records attributed to M Kitajima.

At least 307 records · Page 17Linked to original sources
PubMed1994

The effects of dopamine infusion on the postoperative energy expenditure, metabolism, and catecholamine levels of patients after esophagectomy.

Although dopamine is one of the most widely used vasoactive agents, its postoperative thermogenic and metabolic effects have not been studied. In this study, the effects of low-dose dopamine, given at 5 microgram/kg/min, on resting energy expenditure (REE), metabolism, and plasma catecholamine levels were examined in eight postsurgical patients. Dopamine infusion increased REE from 1,839 +/- 171 kcal/day to 2,071 +/- 170 kcal/day, and it decreased to 1,867 +/- 141 kcal/day after cessation of the infusion. Dopamine also increased the plasma levels of glucagon from 109.4 +/- 8.7 pg/ml to 132.5 +/- 8.0 pg/ml, and it decreased to 102.9 +/- 11.1 pg/ml after cessation of the infusion. The plasma levels of dopamine before, during, and after the infusion were 116.1 +/- 18.3, 161.1 +/- 25.6 and 121.4 +/- 17.2 ng/ml, respectively. Insulin and glucose were affected by dopamine, but changes in their plasma levels did not parallel the dopamine levels. Epinephrine and norepinephrine were increased by the infusion of dopamine and continued to increase even after its cessation. The results of this study revealed that low-dose dopamine increased REE in postsurgical patients and that this might be associated with the concomitant increase in plasma glucagon.

Aged↗
PubMed1994

Gene expression of interstitial collagenase (matrix metalloproteinase 1) in gastrointestinal tract cancers.

Collagenolytic proteinases play an important pathological role in the invasion and metastasis of cancer cells. However, little is known about the role of interstitial collagenase (matrix metalloproteinase-1; MMP-1) in this process. To investigate the expression of the MMP-1 gene in cancer tissues, an in situ hybridization study was carried out in gastrointestinal tract cancers (one esophageal cancer, five gastric cancers, and four colorectal cancers), using a 35S-labeled MMP-1 cDNA probe. The MMP-1 gene was expressed in the stromal cells of fibrous tissue around cancer nests, especially at the margin of invasion and/or within the cancer nest; however, no definite expression within cancer cells was observed. Expression of the MMP-1 gene in the stromal cells was more common in well differentiated gastric adenocarcinoma than in poorly differentiated adenocarcinomas. These findings indicate that expression of the MMP-1 gene is greater in stromal cells that are closely associated with cancer cells, suggesting a pathophysiological role of MMP-1 in the invasion and metastasis of cancer cells.

Adenocarcinoma↗
PubMed1994

cDNA cloning and characterization of mitochondrial import stimulation factor (MSF) purified from rat liver cytosol.

We identified a liver cytosolic protein factor that stimulated the import of wheat germ lysate-synthesized precursor proteins into mitochondria. It was termed mitochondrial import stimulation factor or MSF [Hachiya, N. et al. (1993) EMBO J. 12, 1579-1586]. It consisted of 32-kDa (MSFL) and 30-kDa (MSFS) polypeptides as assessed by SDS-PAGE. MSF recognized the presequence portion of mitochondrial precursor proteins and catalyzed the depolymerization and unfolding of in vitro synthesized mitochondrial precursor proteins in an ATP-dependent manner. We report here the cDNA cloning and characterization of MSF. Microsequencing of MSFL and MSFS showed that they belonged to a highly conserved, widely distributed eukaryotic protein family, collectively designated as 14-3-3 proteins. We cloned the cDNA of MSFL and that of one component of MSFS (MSFS1) from a rat liver cDNA library. The cloned cDNAs were separately expressed in Escherichia coli and the expressed proteins were purified to homogeneity. The purified recombinant MSFL and MSFS1 stimulated mitochondrial import of adrenodoxin precursor (pAd) synthesized in vitro with wheat germ lysate translation system. Recombinant MSFL or MSFS1 had the ability to bind with denatured pAd and they kept the precursor in an import-competent state. Rabbit polyclonal antibodies raised against the recombinant proteins inhibited the import-stimulation activity of rat liver cytosol as well as that of authentic purified MSF. Identification of MSF as 14-3-3 proteins establishes a novel function for this family of proteins and indicates their role as cytosolic chaperones to aid many important cellular events.

14-3-3 Proteins↗
PubMed1994

Improvement of therapeutic effect by using Fab' fragment in the treatment of carcinoembryonic antigen-positive human solid tumors with adriamycin-entrapped immunoliposomes.

To improve the therapeutic efficiency adriamycin entrapped in antibody-conjugated liposomes, Fab' fragment was used instead of the whole antibody molecule. The murine monoclonal antibody, 21B2, against human carcinoembryonic antigen (CEA) was digested with pepsin, and the thiol residue of intra-heavy chain produced by reduction of F(ab')2 with dithiothreitol was conjugated to liposomes containing adriamycin. The tissue distribution of adriamycin delivered with these liposomes was studied in BALB/c nu/nu female mice bearing CEA-positive human gastric cancer strain MKN-45. An increase in delivery of adriamycin to the tumor was observed in the mice given liposomes with Fab' fragment as compared to those given liposomes with whole antibody. However, the preferential distribution of adriamycin in liposomes to the reticuloendothelial cells remained the same regardless of the use of Fab' fragment. For investigation of in vivo therapeutic effect, three i.v. injections of free adriamycin or adriamycin in liposomes equivalent to 5 mg/kg were given, and adriamycin in Fab' fragment-conjugated liposomes was found most effective in the inhibition of tumor growth. This was confirmed in terms of actual tumor weights excised and CEA concentration in the blood, as well as by pathological observations. The advantages of using Fab' fragment instead of whole antibody are discussed.

Animals↗
PubMed1994

Single-cell suspension assay with an MTT end point is useful for evaluating the optimal adjuvant chemotherapy for advanced gastric cancer.

One hundred and forty-eight patients with gastric cancer admitted to Keio University Hospital between July 1988 and October 1992 underwent resection of the primary lesion, as well as single-cell suspension assay of fresh surgical materials with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) for chemosensitivity evaluation. Fifty patients with histologically stage III or IV gastric cancer were enrolled in this study, among whom 10 received no chemotherapy after surgery while 40 received chemotherapy at equivalent dose levels after surgery. The patients given chemotherapy were divided into two groups consisting of an "Adapted" group treated with at least one agent identified as effective by the assay, and a "Non-adapted" group treated with agents to which the cells were not sensitive in the assay, in order to identify the optimal cut-off inhibition rate (IR) in MTT assay for evaluation of the appropriate adjuvant cancer chemotherapy after surgery. A cut-off IR of 30% was optimal for differentiating the survival rates between the "Adapted" and "Non-adapted" groups. Patients treated with drugs which showed more than 30% IR on their surgical specimens showed a better survival rate than patients treated with drugs which were ineffective in the assay.

Adult↗
PubMed1994

Paradoxical enhancement of tumor growth in mice with severe combined immunodeficiency which produce a human immunoglobulin G reactive against tumor cells.

Mice with severe combined immunodeficiency reconstituted with human splenic tissue (SCID-sp) taken from 22 patients with advanced gastric cancer and 8 with idiopathic thrombocytopenic purpura (ITP) received subsequent implants of COLO 205 human colon cancer cells. A human immunoglobulin G (IgG) reactive against COLO 205 cells (COLO 205-reactive human IgG) was produced by SCID-sp mice reconstituted with splenic tissue from 8 of the 22 gastric cancer patients, but from none of the ITP patients. Tumor growth in SCID-sp mice which produced the COLO 205-reactive human IgG was greater (tumor weight range, 106-143%) than that in the control SCID mice, while that in SCID-sp mice reconstituted with splenic tissue from 8 ITP patients and that in SCID-sp mice reconstituted with splenic tissue from the other 14 gastric cancer patients which did not produce the COLO 205-reactive IgG were considerably lower and slightly lower, respectively, than those in the control SCID mice (tumor weight range, 56.7-108% and 79.4-119%, respectively). When the COLO 205-reactive human IgG titers in the sera of the SCID-sp mice, expressed as a ratio of the titers in the corresponding patient's serum, were plotted against the tumor weight in each SCID-sp mouse, significant correlations were observed in those that received splenic tissues from 6 of the 8 patients in which the COLO 205-reactive human IgG was produced. Furthermore, the tumor growth rates increased in proportion to the increased COLO 205-reactive human IgG titers in SCID-sp mice. Therefore, the SCID-sp model should be useful to study the paradoxical tumor growth possibly due to impaired immune reaction in patients with advanced gastric cancer.

Animals↗
PubMed1994

Hypertrophic olivary degeneration: MR imaging and pathologic findings.

PURPOSE: To assess magnetic resonance (MR) imaging findings of hypertrophic olivary degeneration (HOD) due to hemorrhage and correlate them with pathologic findings. MATERIALS AND METHODS: MR imaging was performed in 11 patients--eight with pontine tegmental hemorrhages (THs) and three with cerebellar hemorrhages in the dentate nuclei. The interval from hemorrhagic ictus to the MR studies was 3 weeks to 49 months. Pathologic specimens came from a woman who died of brain stem hemorrhage. RESULTS: Involvement of the central tegmental tract produced ipsilateral HOD; that of the dentate nucleus or superior cerebellar peduncle produced contralateral HOD. Bilateral olivary changes occurred only when the TH also involved the superior cerebellar peduncle. In bilateral THs, HOD was limited to the dominant bleeding side because of the lateral position of the central tegmental tract. Hyperintense areas of the oliva appeared 3 weeks after ictus. Hypertrophy appeared after 5-15 months. Microscopically, vacuolar degeneration of neurons and hypertrophy of astrocytes with gliosis were seen. CONCLUSION: MR images may depict very early neuronal changes in the oliva and are well correlated with pathologic staging.

Adult↗
PubMed1994

[Clinical study of serum ErbB-2 protein using sandwich radioimmunometric assay (ErbB-2 IRMA 'Eiken')].

Sandwich radioimmunometric assay (ErbB-2 IRMA 'Eiken') was developed to determine the levels of c-erbB-2 oncogene product (ErbB-2 protein) in human sera, and a clinical investigation was carried out to evaluate this novel oncogene product. The mean serum concentration of the ErbB-2 protein determined from 364 donors was 4.0 +/- 0.69 ng/ml (mean +/- SD) for females and 4.5 +/- 0.96 ng/ml for males. Cut-off values were set at 5.4 ng/ml for females and 6.5 ng/ml for males. The positivities of serum ErbB-2 protein in patients with breast carcinoma were 13.0% for primary cases and 47.9% for recurrent cases. Patients with hepatic disorders also had positive serum ErbB-2 protein levels, ie, 43.8% (7/16) for hepatocellular carcinoma and 28.9% (11/38) for hepatitis and liver cirrhosis, although the increase was slight and barely exceeded 10 ng/ml. In comparison with the levels of other tumor markers, such as CEA, CA 15-3 and NCC-ST 439, the serum ErbB-2 level was shown to have poor correlations, and was thus assumed to be useful for combination with those tumor markers. In serial determinations of serum ErbB-2 protein in two patients with recurrent breast carcinoma, the antigen increased preceding the increases in the other tumor markers, thereby also showing usefulness as a monitoring marker for breast carcinoma. In conclusion, these results indicated that ErbB-2 measurement improves the assessment of breast cancer in combination with other tumor markers and is useful as a tool for monitoring the clinical condition and the response for treatment in breast cancer.

Aged↗
PubMed1994

[Clinical evaluation of serum ErbB-2 protein using enzyme immuno assay (ErbB-2 EIA [Nichirei])].

The levels of ErbB-2 protein in serum samples from patients with breast cancer, other various malignant tumors, and benign diseases were determined using the sandwich EIA for clinical evaluation. In 364 healthy blood donors, cut-off values were set at 5.4 ng/ml for females and 6.5 ng/ml for males. The positive rate of primary breast cancer was 13.0% (24/185) and that of recurrent breast cancer was 51.2% (62/121). No significant correlation was found between serum levels of ErbB-2 protein and other tumor markers, such as CEA, CA 15-3, and ST 439. Measurement of ErbB-2 protein in combination with these tumor markers showed increased sensitivities. The positive rates and levels of ErbB-2 protein in sera of patients with metastasis to multiple organs were significantly higher than those in patients with metastasis to only a single organ. In postoperative follow-up of two patients with recurrent breast cancer, the levels of ErbB-2 exceeded its cut-off value a few months earlier than did the other tumor markers. These results indicate that the measurement of the ErbB-2 protein in serum is useful for the diagnosis and a monitoring the relapse of breast carcinoma.

Biomarkers, Tumor↗
PubMed1994

[Abnormalities and clinical characteristics of growth factors and receptor systems in breast cancer].

Recent progress in molecular biology has revealed that the proliferation of breast cancer is controlled by various growth factors and their receptors. In particular, the amplifications and products of oncogenes which code growth factors and receptors can be different indicators of clinical malignancy from the conventional prognostic factors. We investigated the relation of c-erbB-2 and int-2 gene amplification, expression, ER and EGFR with clinical characteristics. In retrospective study, the cumulative 10-year survival rate of patients with c-erbB-2 and int-2 gene amplification was significantly lower than in patients without amplification. In 72 cases with tumor diameter less than 3.0 cm, which can be an indication of breast preservation surgery, the survival rates of patients in these gene amplified groups were significantly lower than in the non-amplified groups. As for prospective study, the results were the same as those from retrospective study. These data show that the cases with these gene amplification have a high biological malignancy and high risk of recurrence to distant organs, despite the small tumor diameter.

Breast Neoplasms↗
PubMed1994

[Clinical evaluation of ErbB-2 protein in tissue extract using an enzyme immuno assay (ErbB-2 EIA "Nichirei")].

ErB-2 protein levels in breast cancer tissue extracts were determined by an enzyme immuno assay (ErbB-2 EIA "Nichirei") using anti-c-erbB-2 monoclonal antibodies, and compared with the c-erbB-2 gene amplification detected by dot blot hybridization or differential PCR, and with the overexpression detected by immunostaining. The positivities of c-erbB-2 gene amplification and overexpression in breast cancer tissues were 25.0% (14/56) and 39.3% (46/117), respectively. The cut-off values of the Erb B-2 protein in tissue extract by EIA were set at 18.0 ng/mg-protein for gene amplification and 10.4 ng/mg-protein for overexpression, respectively, from the data of breast cancer tissues which were negative for c-erbB-2 gene. The accuracy of the ErbB-2 protein levels in tissue extract with c-erbB-2 gene amplification and overexpression were 90.6% and 79.2% using these cut-off values respectively. The result of c-erbB-2 gene amplification, overexpression, and ErbB-2 protein levels were significantly correlated with negative estrogen receptor (ER) and progesterone receptor (PgR) status in tissue cytosol fraction. These results indicate that measurement of ErbB-2 protein in tissue extract is useful to estimate the c-erbB-2 gene amplification and/or overexpression in breast cancer tissues.

Antibodies, Monoclonal↗
PubMed1994

[An early phase II clinical study of RP56976 (docetaxel) in patients with breast cancer].

An early phase II clinical study of RP56976 (docetaxel), a new anticancer agent of plant origin, was conducted in patients with breast cancer at 20 Japanese collaborative institutions. Docetaxel was administered at two or more doses of 60 mg/m2 by intravenous infusion with dose-free intervals of 3-4 weeks, and the efficacy and safety was evaluated. Of the 51 patients enrolled, 50 patients completed the scheduled course of treatment. Two patients showed a complete response (CR) and 19 showed a partial response (PR) with a response rate of 42.0%. The response rates based on the efficacy for metastatic lesions in soft tissue, liver and lung, were 46.2% (18/39), 37.5% (3/8), and 38.5% (5/13), respectively. Of the 50 patients who completed the study, 48 patients had previously been treated for the present malignancy. Forty-seven patients had previously been treated with chemotherapy and showed a response rate of 40.4% (19/47). The response rate in those who had received chemotherapy composed of anthracyclines and other agents was 44.1% (15/34). Grade 3 or more severe leukopenia and neutropenia developed in 43 patients (84.3%) and 48 patients (94.1%), respectively. Other adverse reactions which occurred in a Grade 3 or more severe form included nausea/vomiting (1 patient), anorexia (5 patients), diarrhea (4 patients), fatigue (2 patients), and alopecia (20 patients). Except for alopecia, most adverse reactions were generally transient and reversible without any specific treatment.

Adult↗