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Biomedical subjects

K Baba

Publications and source records attributed to K Baba.

At least 181 records · Page 10Linked to original sources

Rat liver fatty acid-binding protein: identification of a molecular species having a mixed disulfide with cysteine at cysteine-69 and enhanced protease susceptibility.

Fatty acid-binding protein (FABP) has been isolated from rat liver cytosol by two steps of gel-permeation chromatography on Sephadex G-75 and Sephacryl S-100 after ammonium sulfate precipitation. FABP fraction was eluted as two well-separated peaks, fractions A and B, by reversed-phase high-performance liquid chromatography (HPLC). The structural difference between the two fractions was investigated by lysyl endopeptidase digestion followed by reversed-phase HPLC of the digests, which identified a peptide corresponding to residues 58 through 78 as the modified peptide. Matrix-assisted laser-desorption-ionization mass spectrometry and other chemical analyses of the peptides established the modification in fraction A as cystein-thiolation at cysteine-69. This was confirmed by reduction and reoxidation of the peptide and the parent molecules. The modification did not affect binding of fluorescent derivatives of fatty acids. However, the modified species was more susceptible to proteolysis by bovine spleen cathepsin B and cathepsin D than the unmodified species. The presence of a relatively large amount of cysteine (but not of glutathione) mixed-disulfide form of FABP suggests some physiological role of this modification related to the redox status of the cell [Thomas, J.A., Poland, B., and Honzatko, R. (1995) Arch. Biochem. Biophys. 319, 1-9], and accounts, at least in part, for the extensive heterogeneity of liver FABP.

Amino Acids↗

Expression of MAGE genes in human colorectal carcinoma.

OBJECTIVE: The human genes MAGE-1 and -3 encode tumor-specific peptide antigens, which are recognized by autologous cytotoxic T lymphocytes. The antigens coded by those genes may be useful for cancer immunotherapy. There is, however, little information on the expression of these genes in human colorectal carcinomas. METHOD: The expression of MAGE-1, -2, and -3 genes in 54 pairs of tumor and corresponding normal tissue specimens of the colorectum was determined by means of reverse transcription polymerase chain reaction. The induction of MAGE-1, -2, -3, and -4 gene expression in eight colorectal carcinoma cell lines also was examined by use of a demethylating agent, 5-Aza-2'-deoxycytidine (DAC). RESULTS: The expression of MAGE genes was not recognized in normal colorectal tissues at all. In tumor tissue specimens, the expression of MAGE-1, -2, and -3 was recognized in 16 (30%), 15 (28%), and 11 (20%) patients, respectively. The expression was seen frequently in patients with liver metastasis (p < 0.01). Although MAGE-1 or -3 genes were not induced by DAC, MAGE-2 or -4 genes were induced in three of four MAGE-2 negative cell lines or three of seven MAGE-4 negative cell lines, respectively. CONCLUSIONS: The MAGE genes were expressed exclusively in tumor tissues of one third of patients with colorectal carcinoma. The identification of such tumor rejection antigens is considered to uncover a new possibility for the specific immunotherapy of colorectal carcinoma. The demethylating agent may increase the number of patients who might be candidates for MAGE-specific immunotherapy.

Antigens, Neoplasm↗

Genetic screening in hereditary multiple endocrine neoplasia type 1: absence of a founder effect among Japanese families.

Ten Japanese families with hereditary multiple endocrine neoplasia type 1 (MEN1) were examined. Five DNA polymorphic markers on the long arm of chromosome 11 were analyzed for genetic screening of MEN1 in members of affected families, and disease carriers were identified before clinical manifestations. Unlike MEN1 families in Newfoundland or in Tasmania, no consistent haplotypes were segregated with the disease in the Japanese families when defined by 5 nearby markers. The identification of asymptomatic disease carriers is of substantial clinical importance for early management, genetic counseling and to avoid unnecessary screening for non-disease carriers. However, genetic screening of family members by polymorphic markers could be useful only to each family, and no generally applicable markers were found for Japanese subjects with MEN1.

Adult↗

Influence of experimental occlusal discrepancy on masticatory muscle activity during clenching.

The influence of the experimental occlusal discrepancy on masticatory muscle activity was investigated on 12 subjects. Specially designed occlusal interferences were fabricated and various occlusal states were simulated with their aid. Subjects were asked to carry out eccentric clenching efforts and electromyographic activity of the masseter plus the anterior and posterior temporal muscles was measured. When compared with clenching on the unaltered natural dentition, clenching on the experimental interferences resulted in distinct patterns in the jaw elevator muscles, and the most characteristic change was observed when clenching effort was exerted on the experimental non-working side interference. Electromyographic activity in the anterior and posterior temporal muscles was decreased on the working side and increased on the non-working side and originally unilateral activity pattern with clear dominance on the working side was altered to a bilateral pattern, while that of the masseter muscles remained uninfluenced. Resultant bilateral activity in the anterior and posterior temporal muscles is thought to cause a superior movement of the working side condyle and an inferior movement of the non-working side condyle.

Adult↗

Treatment of children with congenital heart disease and growth retardation with recombinant human growth hormone.

Seven prepubertal short children with congenital heart disease were treated with recombinant human growth hormone (GH). Although complete surgical correction was performed for their heart disease at least 2 years before the start of GH therapy, improvement in growth was less than expected in these children. They received 0.5 IU kg-1 week-1 of GH daily for 2 years or more. The growth rate increased from a mean of 4.3 cm year-1 before treatment to a mean of 7.8 cm year-1 in the first year and to a mean of 6.3 cm year-1 in the second year of treatment. Their mean standardized height improved from -3.41 +/- 0.78 to -2.54 +/- 0.62 after 2 years. The mean height age difference minus the bone age difference became positive in these children. We conclude that recombinant GH increases the growth rate in children with congenital heart disease and prepubertal growth retardation.

Child↗

Inhibition of aldosterone production by adrenomedullin, a hypotensive peptide, in the rat.

Recently, we conducted in vitro studies and reported that adrenomedullin, a novel hypotensive peptide, inhibits aldosterone secretion by dispersed rat adrenal zona glomerulosa cells. To assess the physiological role of this inhibitory effect, we investigated the effect of adrenomedullin on aldosterone production in vivo. Male Sprague-Dawley rats were fed a normal sodium diet before the experiments. To begin the experimental procedure, we stimulated aldosterone production with a sodium-deficient diet or bilateral nephrectomy. After 3 days of sodium depletion or immediately after nephrectomy, we injected synthetic human adrenomedullin (2.5 nmol/kg SC) and repeated the injection three times at 6-hour intervals. Two hours after the last injection, the rats were decapitated and adrenal capsular tissue was collected. Adrenomedullin had no effect on plasma and adrenal aldosterone concentrations in the rats fed a normal sodium diet. Rats fed a sodium-deficient diet had significantly increased aldosterone concentrations in both plasma (4770.1 +/- 364.3 pmol/L) and adrenal gland (57.34 +/- 3.27 pmol per adrenal). Subsequently, injection of adrenomedullin significantly inhibited increases in concentrations (plasma, 2648.9 +/- 313.2 pmol/L; adrenal, 44.28 +/- 4.94 pmol per adrenal). In nephrectomized rats, increased aldosterone concentrations in plasma and adrenal gland were also significantly inhibited by adrenomedullin. In the second part of the study, plasma renin concentration, adrenal renin activity, plasma corticosterone concentration, serum potassium concentration, and plasma immunoreactive adrenomedullin concentration were examined for adrenomedullin effects. The first four were unaffected, and the last, plasma immunoreactive adrenomedullin, was elevated 15% to 30%. These in vivo results, together with our in vitro data, suggest that adrenomedullin may indeed play a physiological role in the control of blood pressure and electrolyte balance.

Adrenomedullin↗

[Prognostic factors of colon cancer from a molecular biology standpoint].

It has been reported that several genes may be good indicators for determining biological behavior, including the prognosis, of colorectal cancers. We have summarized these reported genes, such as tumor suppressor gene, oncogenes, metastasis suppressor gene, adhesion molecules, growth factors, proteinases, and others, including microsatellite instability. Some of the genes such as p53, DCC, c-met, or matrix metalloproteinase are considered to be reliable for determining biological aggressiveness. We introduced several interesting genes which we are focusing using cDNA subtraction library analysis. We hope that these genes are well combined for best analysis of the biological behavior of colorectal cancers and use for practical clinical analysis. In addition, we hope that novel important genes indicative for prognosis will be found.

Chromosome Deletion↗

[An operative case of suture-granuloma which resulted from an intra-pulmonary treatment 10 years ago and manifested hemoptysis].

We experienced a 27-year-old male patient with recurrent hemoptysis manifested by granuloma which resulted from surgical repair that was performed for right pneumothorax using unabsorbable sutures (braided silk) before 10 years. The patient had been suffering from fever and cough for three months before hemoptysis. Chest X-ray and CT scan films showed a mass shadow in the lateral side of the right lung field. Furthermore, bronchoscopy revealed bleeding in B3 of the right lung. The patient underwent right upper lobectomy, which disclosed that hemoptysis was due to a granuloma (2.3 x 3.2 cm in size) formed around sutures. The granuloma was caused not only by foreign body reaction but also by transbronchial infection.

Adult↗

Expression of BAGE, GAGE, and MAGE genes in human gastric carcinoma.

The MAGE, BAGE, and GAGE genes code for distinct antigens that are recognized by autologous cytolytic T lymphocytes. We investigated the expression of these genes in both cell lines and surgical samples of gastric carcinoma, using reverse transcription-PCR. Furthermore, the induction of these genes by 5-aza-2'-deoxycytidine (DAC), a demethylating agent, was also examined in several cell lines. Of 11 cell lines, BAGE, GAGE1-6, GAGE1-2, MAGE-1, and MAGE-3 were detected in 7 (64%), 4 (36%), 3 (27%), 8 (73%), and 8 (73%) cell lines, respectively. After the in vitro treatment of the negative cell lines with DAC, the expression of these genes became positive in 46 to 91% of these cell lines. No expression of these genes was seen in any of the 57 samples of normal gastric tissue. In contrast, the tumor tissue samples expressed BAGE, GAGE1-6, GAGE1-2, MAGE-1, and MAGE-3 in 13 (23%), 9 (16%), 6 (11%), 25 (44%), and 23 (40%) tissue samples, respectively. Thus, at least one of these genes was expressed in 35 (61%) of 57 carcinomas. An analysis of the relationship between clinicopathological factors and the expression of these genes revealed that either BAGE or one of these genes was more frequently expressed in histologically intestinal-type than in diffuse-type carcinomas. Our results suggest that, because of the higher expression of these genes and the possible induction of these genes by DAC, patients with gastric carcinoma may, therefore, be potential candidates for tumor-specific immunotherapy directed against these antigens.

Aged↗

Benefits of Medroxyprogesterone Acetate (MPA) in Advanced or Recurrent Breast Cancer with Higher Serum Concertration.

The efficacy of medroxyprogesterone acetate (MPA) therapy in controlling progressive measurable metastatic breast cancer was assessed in 61 patients. In addition serum MPA concentrations were measured by high performance liquid chromatography (HPLC) and subjective effects of treatment were monitored. Overall 24 patients (39.3%) achieved an objective response(2 complete responses [ CR ] and 22 partial responses [ PR ]). There was no significant relationships between response to therapy and menopausal status, metastatic sites, previous therapy, histological type, or disease-free interval. Patients with estrogen (ER) and progesterone (PgR) receptor-positive tumors responded more frequently. Significant differences in serum MPA concentrations were seen between responders and non-responders, objective tumor shrinkage being seen in patients with serum levels in excess of 55 ng/ml. There were few cases responding to the therapy with serum MPA concentrations lower than 25 ng/ml. The serum MPA levels significantly correlated with an improvement in the performance status and survival. Patients with serum MPA concentrations lower than 25 ng/ml had significantly poorer survival. There was a significant relationship between MPA level and dose per area of boby surface (mg/ m(2)) in cases with CR or PR or no change (NC). However, the serum levels of patients with progressive disease despite therapy were lower than the expected levels based on the body surface area. This study demonstrated that serum MPA concentration is a determining factor for therapeutic benefit in advanced or recurrent breast cancer.

Journal Article↗

Enkephalin-immunoreactive fastigial neurons in the rat cerebellum project to upper cervical cord segments.

By using enkephalin immunohistochemistry combined with retrograde fluorescent labelling, a great majority of neurons in the rat cerebellum sending their axons to the spinal cord were shown to contain enkephalin immunoreactivity. These neurons were numerous and clustered in the fastigial nucleus but far less abundant in other cerebellar nuclei. Enkephalin-immunoreactive fibers present in the ventral horn and the central cervical nucleus of upper cervical cord segments almost completely disappeared contralaterally following kainic acid-induced cell loss in the fastigial nucleus. The results indicate that fastigial and some other cerebellar nucleus neurons provide enkephalin-containing projections toward these spinal sites.

Animals↗

Immunohistochemical evidence for enkephalin and neuropeptide Y in rat inferior colliculus neurons that provide ascending or commissural fibers.

Enkephalin- and neuropeptide Y-expressing neurons which offer commissural axons or axons toward auditory thalamus were identified in the rat inferior colliculus. These neurons exhibited a differential distribution pattern. The results provide evidence for regional specificity and chemical heterogeneity of neurons in the auditory midbrain.

Afferent Pathways↗

Microsatellite instability in Japanese esophageal carcinoma.

Recent studies have shown that microsatellite instability (MSI) may play an important role in the development of various types of cancer. However, there have been only 2 reports describing MSI in esophageal carcinoma and the clinicopathologic significance of MSI in this malignancy has not yet been clarified. To better elucidate the role of genetic instability in the development of esophageal carcinoma, we investigated the presence of MSI in 32 cases of esophageal cancer using paired samples of fresh frozen tumor and normal tissue by a method based on the polymerase chain reaction. MSI was defined as occurring in tumors which showed altered banding patterns at one or more microsatellite loci. The incidence of MSI in esophageal carcinoma was 6 out of 32 patients. MSI was observed more frequently in cases with small-cell carcinoma (2 out of 2) than in cases with squamous-cell carcinoma (4 out of 29). No cases with adenocarcinoma or Barrett's metaplasia were included in our series. No significant correlations between MSI and other clinicopathologic parameters were observed. The present study suggests that (1) some Japanese esophageal carcinomas certainly correlate with DNA replication error, and (2) MSI may be more frequent in small-cell carcinoma of the esophagus than in squamous-cell carcinoma of the esophagus.

Aged↗

An Evaluation of DNA Polymerase alpha as a Prognostic Predictor in Early Breast Cancers Smaller than 2 cm.

We examined the relationship between proliferative activity determined by DNA polymerase alpha and clinicopathologic variables in breast cancer patients, and evaluated the usefulness of DNA polymerase alpha as a prognostic predictor in 337 early breast cancers with tumors smaller than 2 cm, which had favorable outcomes. About 60% of tumors had lower proliferative activity. A significant correlationwas found between DNA polymerase alpha and ER, PgR, histological type, or the degree of infiltration into lymphatic vessels which reflect the prognosis. Cancers with higher DNA polymerase alpha activity were associated with shorter disease-free and overall survival times. In a multivariate analysis the DNA polymerase alpha was found to be an independent and significant factor in early breast cancer.

Journal Article↗