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Biomedical subjects

T Baba

Publications and source records attributed to T Baba.

At least 55 records · Page 3Linked to original sources

Three-dimensional study of the cytoskeleton in macrophages and multinucleate giant cells by quick-freezing and deep-etching method.

The three-dimensional ultrastructure of multinucleate giant cells in subcutaneous granulomas was compared with those of peritoneal macrophages using a quick-freezing and deep-etching method. Subcutaneous granulomas were induced by implanting plastic coverslips in the dorsal subcutaneous tissue of rats. The quick-freezing and deep-etching replicas were prepared from the cells attached to the coverslips. Dense networks of actin filaments were distributed along all peripheral aspects (beneath the plasma membrane, and on free and coverslip-attached surfaces) of the multinucleate giant cells. On the coverslip-attached surface, numerous clathrin-coated pits and vesicles occurred between the actin filaments. In these cells, intermediate filaments, but not actin filaments, were the predominant cytoskeletal components in perinuclear regions and were attached to the cell nucleus, mitochondria and other vesicular cell organelles. A similar distribution of cytoskeletal components was observed in the mononuclear macrophages of the granulomas and the peritoneal macrophages. These results show that the cytoskeletal organization varies in different regions of the cytoplasm of multinucleate giant cells, while the characteristic cytoskeletal arrangement, resembling that of mononuclear macrophages, is maintained.

Actins

Intracarotid infusion of leukotriene C4 selectively increases blood-brain barrier permeability after focal ischemia in rats.

Intracarotid infusions of leukotriene C4 (LTC4) were used to open selectively the blood-brain barrier (BBB) in ischemic tissue after middle cerebral artery (MCA) occlusion in rats. BBB permeability was determined by quantitative autoradiography using [14C]aminoisobutyric acid. Seventy-two hours after MCA occlusion, LTC4 (4 micrograms total dose) infused into the carotid artery ipsilateral to the MCA occlusion selectively increased the unidirectional transfer constant for permeability Ki approximately threefold within core ischemic tissue and tissue adjacent ot the ischemic core. No effect on BBB permeability was seen within nonischemic brain tissue or in ischemic tissue after only 24 h after MCA occlusion. gamma-Glutamyl transpeptidase (gamma-GTP) activity was decreased in capillaries in ischemic tissue at 48 and 72 h after infarction, compared to high gamma-GTP in normal brain capillaries and moderate gamma-GTP in capillaries in the ischemic tissue at 24 h after infarction. These findings suggest that normal brain capillaries resist the vasogenic effects of LTC4. In contrast, LTC4 increases permeability in capillaries of ischemic tissue, where gamma-GTP is decreased. gamma-Glutamyl transpeptidase, an enzyme that inactivates LTC4 to LTD4 and LTE4 to LTF4, may act as an "enzymatic barrier" in normal brain capillaries to leukotrienes.

Animals

Structure and organization of the mouse acrosin gene.

The genomic region carrying the mouse acrosin gene, including the 5'-flanking sequence, has been isolated and characterized. The acrosin gene consists of five exons separated by four introns. Organization of this gene is very similar to those of the genes for other typical serine proteases, except for the phase class of the first intron. Riboprobe mapping and primer extension analyses showed that the start site of transcription initiation in the acrosin gene is heterogeneous, including three major sites. Thus, the structure and organization of the mouse acrosin gene are different from those of the human gene [Keime, S., Adham, I.M., & Engel, W. (1990) Eur. J. Biochem. 190, 195-200] in two respects: the number of transcription initiation sites and the phase class of the third intron. The putative promoter regions of the mouse and human acrosin genes lack typical sequences of TATA, CAAT, and GC boxes, but contain a consensus sequence, GGGTGGG, known to be specific for the phosphoglycerate kinase-2 gene, and the protamine-1 and 2 genes that are uniquely expressed during spermatogenesis.

Acrosin

Differentiation disorders of keratinocytes in seborrheic keratosis (acanthotic type).

Since the differential disorder of keratinocytes in seborrheic keratosis remains to be elucidated, the differentiation of seborrheic keratosis (acanthotic type) was examined immunohistochemically using a lectin and two anti-keratin monoclonal antibodies. A lectin, peanut agglutinin (PNA), and anti-keratin monoclonal antibody, 34 beta B4, recognize the whole epidermis except for the basal layer in the normal epidermis. In seborrheic keratosis (acanthotic type), cells unstained with either PNA or 34 beta B4 were found throughout the entire tumor. In the upper part of the tumor, some cells appeared to undergo keratinization without expressing the differential markers recognized by PNA or 34 beta B4. Another anti-keratin monoclonal antibody, 34 beta E12, stained the tissues in the same way as in the normal epidermis. Thus it was indicated that, in seborrheic keratosis (acanthotic type), although differentiation was partially maintained, some cells might undergo maturation without expressing the differentiation markers recognized by PNA or 34 beta B4.

Aged

A case of neonatal McCune-Albright syndrome with Cushing syndrome and hyperthyroidism.

We describe a female newborn infant with McCune-Albright syndrome. In addition to the cutaneous pigmentation, she had apparent manifestations of hyperthyroidism and Cushing syndrome since birth. X-ray examinations showed many scattered lucencies in multiple bones. Endocrinological findings were as follows: serum T 4 276 nmol/l; free T 4 125 pmol/l; TSH less than 1 mU/l; serum cortisol greater than 2210 nmol/l; plasma ACTH less than 10 pg/ml; urinary free cortisol 865 nmol/day; estradiol 0.36 nmol/l. Regardless of treatment with antithyroid drugs and an inhibitor of 3 beta-hydroxysteroid dehydrogenase, the patient died of cardiac failure at the age of 4 months. Autopsy findings included a follicle cyst in the right ovary and multinodular hyperplasia in the thyroid and both adrenals. To our knowledge such a severe neonatal form of McCune-Albright syndrome has not been described in the literature.

Adrenal Cortex

Hyperinsulinemia and blood pressure in non-obese middle-aged subjects with normal glucose tolerance.

A possible link between hyperinsulinemia and blood pressure was studied in non-obese subjects with normal glucose tolerance. First, the responses in plasma glucose and serum insulin to an oral glucose load (75-g oral glucose tolerance test) were compared between 42 patients with essential hypertension and 93 normotensive control subjects. Second, of the 93 normotensive subjects, the relations of serum insulin levels to blood pressure, serum cholesterol, and triglycerides concentrations were assessed in 8 hyperinsulinemic (serum insulin level [during fasting, or after glucose loading, or both] greater than 2 S.D. higher than the mean) and 8 pair-matched normoinsulinemic subjects (serum insulin level within 1 S.D. of the mean), individually matched for age, sex, and body mass index. Plasma glucose and serum insulin responses to the glucose load in hypertensive subjects were identical to the respective responses in normotensive subjects, while the mean total serum cholesterol level was slightly higher (p less than 0.05) in hypertensive subjects. The respective values for systolic and diastolic blood pressures, and total serum cholesterol and triglycerides concentrations were comparable in hyperinsulinemic and normoinsulinemic subjects. These results did not suggest a close association between hyperinsulinemia and elevated blood pressure in non-obese middle-aged Japanese subjects with normal glucose tolerance.

Blood Glucose

Differentiation of the basal cell epithelioma-like changes overlying dermatofibroma.

Epidermis overlying dermatofibroma rarely displays basal cell epithelioma-like changes (BCE-like changes). Based on the histopathological findings, whether BCE-like changes are induced by dermal lesion or adnexal regression secondary to the solid fibrotic growth remains to be explored. From the standpoint of differentiation, we examined the BCE-like changes overlying dermatofibroma, normal epidermis, and hair follicles. PNA and two kinds of anti-keratin monoclonal antibodies were used to detect markers for epidermal differentiation. When PNA and anti-keratin monoclonal antibody (34betaB4) were used, no difference was observed in the staining patterns among BCE-like changes, hair follicles or normal basal cells. With the other anti-keratin antibody (34betaE12), BCE-like changes and normal basal cells were recognized, though the hair matrix was not. Thus the results obtained indicate that normal basal cells show the most similar differentiation to BCE-like changes.

Antibodies, Monoclonal

HeLaTG cells have mitochondrial DNA inserted into the c-myc oncogene.

To determine whether mitochondrial DNA (mtDNA) fragments found within the nucleus are transcribed, we have differentially screened a HeLaTG cDNA library. A clone that hybridized to mtDNA as well as to c-myc was identified. Analysis of the cDNA disclosed that it contained a mtDNA sequence, encoding cytochrome-c oxidase subunit III (coxIII) that was contiguous with and 5' of a c-myc sequence corresponding to part of exon 2 and exon 3. Hybridization of ScaI-digested DNA with a 1.05 kb c-myc probe revealed a unique band in HeLaTG cells, as well as a band common to HeLaTG and 13 other cell types examined. Solution hybridization of HeLaTG RNA with a radiolabeled, single-stranded cDNA probe containing the coxIII-c-myc junction demonstrated a nuclease-resistant band that matched the full length of the junctional cDNA probe. A smaller band that equaled the size of the c-myc portion alone was also detected. Only the smaller band coinciding with the c-myc sequences was protected from nuclease digestion by RNA from other cells. When a radiolabeled probe synthesized in the opposite orientation was used, nuclease-resistant bands equal in length to the coxIII portion of the probe were detected after hybridization with RNA from all cells. These results indicate that insertion of mtDNA fragments into nuclear genes occurs and that subsequent transcription of a 'chimaeric' or 'fusion' mRNA containing both mitochondrial and nuclear sequences can ensue.

Base Sequence

Acrosin biosynthesis in meiotic and postmeiotic spermatogenic cells.

It has been widely accepted that mammalian sperm acrosin is first synthesized only in the postmeiotic stages of spermatogenic cells. In this study, we carried out Northern blot analysis of RNAs prepared from purified populations of mouse spermatogenic cells. The acrosin mRNA was obviously found in meiotic pachytene spermatocytes, and the mRNA content markedly increased in postmeiotic round spermatids. Also, the acrosin mRNA in pachytene spermatocytes was functionally associated with polysomes. These results provide evidence that acrosin biosynthesis is already started in meiotic cells and continues through the early stages of spermiogenesis.

Acrosin

Increased therapeutic efficacy of intra-arterial carboquone chemotherapy on a limb tumor in rats, by using an acidic vehicle adjusted with lactate.

We previously reported that the cytotoxicity of carboquone (CQ) was potentiated in vitro and in vivo under acidic conditions. In this study, an acidic vehicle adjusted with lactate at various low pHs was used for CQ intra-arterial (i.a.) injection, in order to enhance the antitumor effects of i.a. CQ chemotherapy. Treatments were evaluated in Wistar/KA rats bearing a limb tumor 5 days after the inoculation of 3 x 10(6) syngeneic RBT-1 tumor cells into the hind limb. In chemotherapy experiments using an intrafemoral injection of CQ at 1.5 mg/kg in phosphate-buffered saline (PBS, pH 7.4) or in an acidic vehicle at pH 5.0 or 6.0, the antitumor effects seen in rats given CQ in acidic vehicles, evaluated by tumor weight 14 days after treatment, were significantly greater than that seen in rats given CQ in PBS. There were no significant differences either in changes of body weight or in the number of leukocytes after treatment between the groups given CQ in PBS and in an acidic vehicle at pH 6.0. Although in the group given CQ at 2.0 mg/kg in PBS, the antitumor effect was the same as that observed in rats given CQ at 1.5 mg/kg in an acidic vehicle at pH 6.0, the side effects observed in the former group were much severer than in the latter group. These data suggest that the antitumor effect of i.a. CQ chemotherapy can be potentiated by using an acidic vehicle.

Animals

Newly identified type of beta actin reduces invasiveness of mouse B16-melanoma.

Low metastatic parent B16 melanoma and isolated B16-F1 cell lines have a third actin designated as beta m(Ax:previously). beta m actin is scantily or not at all detected in highly metastatic cell lines, such as B16-F10 and BL6. To directly assess the physiological role of beta m in phenotypic changes of B16 melanoma, we transfected expression plasmids of beta m into B16-F10 cells. The actin expressed in the transfectants is located largely in cytoskeletal fractions. The transfectants exhibited a larger number of stress fibers and a lower invasiveness than did the recipient cells. Thus, beta m actin plays an important role in the organization of actin stress fibers, the result being a decrease in invasiveness of B16 melanoma.

Actins

Systemic chemotherapy in tumor-bearing rats using high-dose cis-diamminedichloroplatinum(II) with low nephrotoxicity in combination with angiotensin II and sodium thiosulfate.

Systemic chemotherapy using high-dose DDP and its antidote, STS, was combined with the AT-II-induced hypertension method and evaluated for efficacy against s.c. tumors in rats. After i.v. infusion of DDP plus AT-II for 5 min, STS was administered i.v. over a further 5 min. The rats treated with this combination chemotherapy showed normal levels of BUN and serum creatinine 4 days after the treatment, although most rats given i.v. STS after DDP without AT-II showed severe nephrotoxicity. The absence of obvious nephrotoxicity in AT-II-combined chemotherapy using i.v. DDP plus post-administered STS can be explained by a transient inhibition of DDP-delivery to the kidney during the AT-II-induced hypertension. The anti-tumor effect of this modified therapy, evaluated by inhibition of tumor growth, was superior to other treatments, as follows: concomitant i.v. administrations of DDP and STS; i.v. DDP, with or without AT-II. The improvement in anti-tumor effect of this combination therapy is explained by the delayed neutralization of active DDP by STS at the tumor site and the selective enhancement of DDP delivery to the tumor tissue, as produced by AT-II. Thus, systemic chemotherapy using high-dose DDP induced no obvious nephrotoxicity and improved the anti-cancer effect in the case of concomitant administration of DDP plus AT-II and the time-delayed injection of STS.

Angiotensin II

Augmented excretion of procathepsin L of a fos-transferred highly metastatic rat cell line.

We previously reported that v-fos transfer to a src-transformed rat 3Y1 cell line (SR-3Y1-2) enhanced lung metastasis accompanied with an increase in invasiveness. When analyzing factors relating to the high invasiveness, with special reference to typical lysosomal proteases (cathepsins), involving degradation of stroma, we found that the excretion of procathepsin L was significantly larger in the fos-transferred highly metastatic cell line (fos-SR-3Y1-202) than that in the recipient cell lines. The cathepsin D-induced enzyme activity of the excreted procathepsin L in fos-SR-3Y1-202 was about 4 and 13 fold that of SR-3Y1-2 and 3Y1, respectively. The increase in the excretion of procathepsin L from fos-SR-3Y1-202 may play a role in the high invasiveness induced by transfer with the v-fos oncogene.

Animals

Comparison of the renal effects of dilevalol and carteolol in patients with mild to moderate essential hypertension.

The effects of 6 weeks of treatment with dilevalol 100 mg once daily, or carteolol 10 mg once daily, on renal blood flow (RBF), glomerular filtration rate (GFR) and total renal vascular resistance (TRR) were studied in 10 patients with mild-to-moderate essential hypertension in a randomised cross-over experiment. Both drugs lowered the systolic and diastolic blood pressures to a similar extent without altering the heart rate. Carteolol non-significantly decreased RBF by 9.2% and GFR by 12.3% without altering. TRR, whereas dilevalol produced a significant reduction in TRR by 13.2% (p less than 0.05), a non-significant decrease in RBF by 4.6% and no change in GFR. Neither drug changed plasma osmotic pressure, serum total protein concentration, electrolytes or plasma aldosterone concentration. Plasma renin activity tended to be lower in the dilevalol phase as compared to the carteolol phase. The results suggest that dilevalol may cause a greater decrease in TRR and less reduction in GFR when compared to carteolol in patients with mild-to-moderate essential hypertension. The difference in the renal effects might be due to the difference in the potency of vasodilatory properties of both drugs at the doses applied.

Adult