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Biomedical subjects

K Baba

Publications and source records attributed to K Baba.

At least 145 records · Page 8Linked to original sources

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↗

Interaction of filarial proteins on growth regulation of normal lung epithelial cells in vitro.

An in vitro model to examine the effects of filarial proteins on lung epithelial cells has been developed. Several of these proteins appear in circulation of infected individuals. A close association between tropical pulmonary eosinophilia (TPE) and filariasis has been reported by several workers. [3H]-thymidine studies do indicate that when optimum concentration of these filarial proteins were added to lung cultures in proliferating and basal/maintenance media a further increase in growth stimulation was observed early in culture. However, on longer exposures and at higher concentrations an inhibitory effect with distinct morphological changes were noted. The dual role of these proteins on lung epithelial cells in vitro may highlight the possibility of a direct interaction of these proteins with lung cells during disease also contributing to tissue damage.

Animals↗

Capillary-tissue arrangement in the skeletal muscle optimized for oxygen transport in all mammals.

The aim of this computer simulation study is to evaluate the efficiency of capillary networks in the skeletal muscle for oxygen (O2) delivery to tissue for all mammals. This was performed by: (1) employing Krogh's cylinder model for the capillary-tissue system and the minimum volume model for the vascular system, (2) allometrically assessing the muscle blood flow and O2 consumption rate (the main input data) in the resting and exercising states as power functions of body weight from the data reported for several mammals, and (3) calculating the cost-performance of the system from the ratio (maximum O2 uptake of tissue)/(minimum energy expenditure of blood flow supply), as a function of number of capillaries. The results obtained for body weights ranging from 100 g to 1000 kg revealed that for each body weight and metabolic state, the efficiency curve attains a peak at a specific optimum capillary number, and that the calculated values of total muscle mass, capillary density, and capillary flow-rate by using the optimum capillary number and tissue radius during exercise agree remarkably well with those actually measured in various animals. These findings suggest the validity of a working hypothesis that in all mammals, the capillary arrangement in the skeletal muscle is optimized for O2 delivery to tissue during exercise.

Animals↗

Effect of adrenomedullin on aldosterone secretion by dispersed rat adrenal zona glomerulosa cells.

Adrenomedullin, a novel hypotensive peptide, was discovered in human pheochromocytoma. Although adrenomedullin exists also in normal adrenal medulla and several other organs, its effect on steroidogenesis in adrenal cortex has not been studied. We examined the effect of adrenomedullin on aldosterone secretion by the dispersed rat adrenal zona glomerulosa cells. Adrenomedullin (10(-12)-10(-7) M) did not affect basal aldosterone secretion. Adrenomedullin dose dependently inhibited aldosterone secretion stimulated by 10(-9) M angiotensin II and 10 mM potassium, whereas 10(-9) M ACTH-stimulated aldosterone was not significantly inhibited by adrenomedullin. N6,O2'-dibutyryladenosine 3':5'-cyclic monophosphate (db-cAMP, 10(-5)-10(-3) M) and Ca+ ionophore A23187 (10(-8)-10(-6) M) stimulated aldosterone secretion dose dependently, and A23187-stimulated secretion was significantly inhibited by adrenomedullin (10(-8) M), but db-cAMP-stimulated secretion was not inhibited by adrenomedullin. Our data suggest the possibility that adrenomedullin is a novel inhibitory peptide of aldosterone secretion induced by increasing concentration of intracellular free calcium.

Adrenocorticotropic Hormone↗

The precore/core promoter mutant (T1762A1764) of hepatitis B virus: clinical significance and an easy method for detection.

Recently, a new hepatitis B virus (HBV) mutant with HBe antigen-negative phenotype has been characterized, in which one TATA box-like motif of the precore/core promoter had degenerated: most frequently by both A-->T and G-->A mutations at positions 1762 and 1764, respectively. The clinical significance of this mutant is as yet unknown. In our present study, the T1762 A1764 mutant was sought in sera from HBV-infected blood donors and chronic liver disease patients by directly sequencing a PCR-amplified region of HBVDNA. Also, because the A1764 mutation generates a Sau3AI cleavage site (GGTC-->GATC), we digested the PCR products with Sau3AI to see if cleavage would occur at this specific site. Our results mostly corroborated the earlier report but we found a higher-than-predicted frequency of HBe antigen-positive blood donors positive for the mutant (22%). The titres of HBe antigen in these mutant-positive sera were slightly decreased compared to the titres in wild-type HBV infection. In addition, these blood donors had relatively high (though within the normal range) serum alanine aminotransferase (ALT) levels, suggesting that the T1762 A1764 mutation could be used as a sensitive laboratory marker for insidious hepatitis in these otherwise 'asymptomatic' carriers. The Sau3AI assay, which is much more convenient than sequencing, was shown to be useful for the detection of the T1762 A1764 mutant in an extensive number of clinical samples.

Alanine Transaminase↗

Immunohistochemical profile of primary sclerosing lipogranuloma of the scrotum: report of five cases.

Five cases of primary sclerosing scrotal lipogranuloma were examined histologically and immunohistochemically. Every case lacked a history of injection or trauma, and revealed common histological features: a typical granuloma composed of epithelioid cells and multinucleated giant cells, and inflammatory infiltrates of eosinophils, lymphocytes and macrophage/monocytes in the interstitium. Immunohistochemistry disclosed the epithelioid cells and multinucleated giant cells of the granuloma to be monocytes in nature, as both types of cells were positive for lysozyme, alpha-1-antitrypsin, alpha-1-antichymotrypsin, and KP-1. In the interstitium, KP-1 positive monocytes, L-26 positive B lymphocytes, UCHL-1 positive T lymphocytes and S-100 protein positive Langerhans-like cells were frequently found. S-100 protein positive cells could not be detected in the granuloma. Primary sclerosing lipogranuloma of the scrotum, therefore, is a peculiar inflammation characterized by granulomas consisting of monocytes and marked tissue eosinophilia of unknown etiology.

Adult↗

Herpes zoster in a normal child after varicella vaccination.

A healthy 5 year old girl developed herpes zoster in the dermatome supplied by the ophthalmic branch of the fifth cranial nerve 40 months after varicella vaccination. She was admitted to our hospital because of high fever and painful vesicular lesions over the left side of her forehead. She was treated successfully with systemic and topical acyclovir without developing herpetic keratoconjunctivitis. Our acute and convalescent phase evaluations showed that non-specific cellular and humoral immunity was normal. This is the fourth case of herpes zoster developing in an immunocompetent child following vaccination. Unlike the previously reported cases, our patient required hospitalization mainly to prevent ocular involvement. The issue concerning whether the universal introduction of varicella vaccination of normal children will reduce the incidence of the subsequent occurrence of herpes zoster must await further studies involving longer follow-up periods.

Chickenpox Vaccine↗