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Biomedical subjects

Y Sakai

Publications and source records attributed to Y Sakai.

At least 523 records · Page 29Linked to original sources

[Serum IgA-fibronectin complex in children with various renal diseases].

IgA-Fibronectin complex (IgA-FN) has been found in the circulation of patients with IgA nephropathy (IgAN). It has been suggested that circulating IgA-FN is related to IgA deposits in the mesangial area following mesangial matrix expansion in IgAN. We investigated serum IgA-FN in patients with various renal diseases, and examined the relationship between IgA-FN and the clinico-pathological findings. Serum IgA-FN level was measured by enzyme-linked immunosorbent assay (ELISA) in 35 patients with IgAN, 20 patients with Henoch-Schönlein purpura nephritis (HSPN), and other various renal diseases in children. IgA-FN in patients with IgAN was significantly higher than in healthy subjects and patients with minimal change nephrotic syndrome. However some patients with membranoproliferative glomerulonephritis and lupus nephritis had a high level of IgA-FN. The increase in IgA-FN was correlated with macroscopic hematuria and the degree of proteinuria and mesangial matrix expansion in IgAN. Thus, we concluded that the level of IgA-FN is associated with mesangial matrix expansion.

Adolescent↗

Colonization pattern of Pasteurella pneumotropica in mice with latent pasteurellosis.

Colonization pattern of Pasteurella pneumotropica (P. pneumotropica) in mice with latent pasteurellosis was examined with the original selective media, NKBT medium and TGN broth. In the mice of 0 to 15 weeks old, the organism was mainly isolated from the upper respiratory tract, lower intestinal tract, feces and vagina, with the highest isolation rate in the pharyngolarynx. In the pregnant and lactating mice, the organism was isolated from the same sites, but not from the uterus, fetus or mammary gland. In the neonates, the organism was isolated from the respiratory and intestinal tracts within 24hr after birth. The organism was constantly detected in the feces of the 0- to 20-week-old mice, with the highest viable count one week after birth. Through the monitoring of mouse colonies, the pharyngolarynx always showed higher isolation rate than the feces in several mouse strains. These results reveal that the pharyngolarynx is the primary colonization site of P. pneumotropica in mice, and the lower intestinal tract and vagina are also the main sites. Further, frequent isolation of the organism from the feces and vagina, and the results in neonates suggest the mode of the transmission to newborn mice in the colony, i.e., intravaginal infection at the partition, and oro-nasal infection through the maternal feces and saliva.

Animals↗

A point mutation in the bile acid biosynthetic enzyme sterol 27-hydroxylase in a family with cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis (CTX) is a rare familial disorder characterized by progressive neurological dysfunction, atherosclerosis, and xanthomas with sterol storage in the nervous system, vessels, and tendons. Increased serum cholestanol, derived from intermediates of cholesterol catabolism, may possibly be a major cause of the disease. An examination was made of the cDNA encoding cytochrome P450 sterol 27-hydroxylase (CYP27) in hepatic mitochondria, considered a defective enzyme inducing CTX, in a Japanese housewife afflicted with CTX and her family. The proposita and one of her brothers, who also had CTX symptoms and hypercholestanolemia, were found to be homozygotic, carrying a point mutation in the CYP27 gene at Arg104 (CGG) to Trp104 (TGG). The mutant position has a 100% conserved positive charge in all known vertebrate cytochrome P450s and even in bacterial cytochrome P450cam. The mother of the proposita and another brother were both free of CTX symptoms and were heterozygotic for the mutation, although their plasma cholesterol increased moderately. An increase in plasma cholestanol alone would, thus, not appear to be a direct cause of sterol storage in CTX, while CTX is strongly suggested to be caused by defects in both alleles of the CYP27 gene.

Aged↗

[Electron microscopic study on the degeneration and regeneration of the rat liver nerve fibers].

With advances in liver transplantation, attention has been directed to the regeneration of hepatic nerves. In this study, examination is made of ultrastructural degeneration and regeneration of hepatic nerves following severance at a point 8 mm proximal to the portal fissure in the rat liver. Immediately after the operation, distal nerve axons swelled and showed the disappearance of microtubules and neurofilaments. Newly formed axons, small in diameter and containing many microtubules and neurofilaments, could been seen at 2 days after the operation among those that had degenerated. The regenerated axons were surrounded completely by Schwann cells. The Schwann cell processes became shorter at days and regenerated axons were situated in the space between Schwann cell and the basement membrane. Degenerated axons could no longer be seen 14 days after the operation, and regenerating axons increasing in diameter filled the nerve fibers. At 21-30 days, Schwann cell processes gradually extended to enclose regenerating axons, nerve fiber regeneration was complete 42-56 days after the operation. The manner of nerve regeneration was consistent with the results of a previous immunohistochemical study using anti GAP-43 (growth associated protein-43) antibody.

Animals↗

[A case of advanced gastric cancer with multiple liver metastases showing marked response to new combination chemotherapy using 5-FU, THP and MMC (FTM)].

A 67-year-old man with advanced gastric cancer with multiple liver metastases was treated by a new combination chemotherapy using 5-FU, THP and MMC (FTM). After the first course of FTM, both abnormal liver function and the elevated level of serum CA 19-9 were restored. After the second course of FTM, the primary lesion became a small ulcer around cardia. A partial response was recognized both in the primary lesion and in the liver metastases. No serious side effect was observed except for leukocytopenia, which was controlled by G-CSFS. This new combination chemotherapy (FTM) was suggested to be useful even for far advanced gastric cancer.

Adenocarcinoma↗

Expression of epidermal growth factor in suprabasal cells of stratified squamous epithelia: implications for a role in differentiation.

There is a disparity in the fact that epidermal growth factor (EGF) can stimulate proliferation of a wide variety of cells in vitro, yet sites of synthesis for this polypeptide in vivo are generally associated with nonproliferative or differentiated cell populations. Unlike other known mitogenic members of the EGF family of ligands, EGF derives from a large (M(r) approximately 130,000) protein that contains multiple EGF-like domains; some of these domains contain putative Ca(2+)-binding sites. In the present study, the mouse vaginal epithelium was used as a prototype tissue to investigate expression of the EGF precursor by stratified squamous epithelia. Stratification and cornification in this tissue are estrogen dependent. In the fully differentiated epithelium, EGF precursor transcripts were detected by in situ hybridization in suprabasal cells; labeling was not observed in the proliferative basal cell compartment. Amplified transcripts of predicted size were detected in the vaginal organ by the reverse transcription-polymerase chain reaction and Northern hybridization of polyadenylated RNA. Antisera to mature EGF or to the COOH-terminal (cytoplasmic) domain of the precursor localized reactivity exclusively to cells of the granular layer. The staining with the precursor antiserum was localized along cell borders, which supports that this protein is translocated to the cell membrane following synthesis, a known property for precursors of EGF-like ligands. EGF expression was not apparent in the atrophic vaginal epithelium of castrates, which did not present a granular layer. Other stratified squamous epithelia in organs such as skin, esophagus, and tongue also revealed EGF/EGF precursor immunoreactivity in the granular layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Exposure to diethylstilbestrol during a critical developmental period of the mouse reproductive tract leads to persistent induction of two estrogen-regulated genes.

Exposure to estrogens during critical periods of development induces teratogenic and carcinogenic lesions in the reproductive tracts of humans and experimental animals. It is important to determine the molecular and cellular targets of estrogenic chemicals and to establish the mechanisms by which interactions of estrogens with the developing genital tract results in permanent lesions of growth and differentiation. The experiments presented here were designed to examined the effects of neonatal estrogen exposure on the expression of two genes, lactoferrin and epidermal growth factor, that are subject to steroid hormone regulation. Using in situ and Northern RNA hybridization, immunoblotting, and immunohistochemistry, our data demonstrate that exposure to the synthetic estrogen, diethylstilbestrol, during a critical neonatal period results in the persistent ovary-independent induction of mRNA and protein encoded by these two genes in the mouse uterus and vagina. The constitutive expression of lactoferrin and EGF, and probably other estrogen-regulated genes, may contribute to the establishment of a permanently "estrogenized" phenotype which is then instrumental in the development of abnormal tissue morphogenesis, function, and neoplasia in the rodent reproductive tract.

Animals↗

[A case of oligomeganephronia--quantitative measurement of the glomerular surface area and the number of glomeruli with a color image analyzer].

We report here a nine-year-old boy with oligomeganephronia. The patient had proteinuria and morphometric analysis of the renal biopsy specimen confirmed the diagnosis of oligomeganephronia. We employed a color image analyzer (OLYMPUS Corp.) to determine the glomerular surface area and the number of glomeruli per mm2 of the renal cortex of the patient. All the scanned glomeruli showed marked hypertrophy; the mean maximal surface area for the 5 glomeruli was 46 x 10(3) microns 2, which is approximately 4 times larger than that of normal children of the same age. The number of glomeruli per mm2 of the renal cortex of the patient had decreased to 1. 11 per mm2, which is approximately one fourth that of normal controls with IgA glomerulonephritis. The color image analyzer proved to be useful for the diagnosis of oligomeganephronia enabling the quantitative measurement of the glomerular surface area and the number of glomeruli per mm2 of the renal cortex.

Child↗

[An early phase II study of CPT-11 (irinotecan hydrochloride) in patients with hematological malignancies].

An early phase II study of CPT-11 (irinotecan hydrochloride) was conducted in patients with hematological malignancies by 4 administration regimens in a cooperative study involving 13 institutes in Japan. The overall response rate was 23% (7/30) for non-Hodgkin's lymphoma, 33% (1/3) for Hodgkin's disease, 18% (2/11) for acute lymphoblastic leukemia and 7% (1/15) for acute myelogenous leukemia. One PR was also obtained in a patient with chronic myelogenous leukemia. Among responders, 6 relapsed and refractory malignant lymphomas (ML) and 2 relapsed and refractory acute leukemias (AL) were involved. The response rates in ML with the regimens B (40 mg/m2 for 5 days every 3-4 weeks) and C (40 mg/m2 for 3 days every weeks) were 31% (5/16) and 33% (3/9), respectively. The other regimens (regimen A, 200 mg/m2 once a day every 3-4 weeks and regimen D) resulted in no response. Responses in AL were only observed in regimen D (20 mg/m2 twice a day for 7 days every 3-4 weeks). Major toxicities were leukopenia (91%), nausea/vomiting (74%), diarrhea (73%) and anorexia (64%). The incidence of severe gastrointestinal symptoms was higher in regimen B than regimen C. Further studies are warranted to confirm the effectiveness and safety of CPT-11 against ML and AL. The recommended administration schedule was regimen C for ML and regimen D for AL.

Adolescent↗

Cloning of the mouse cDNA encoding DNA topoisomerase I and chromosomal location of the gene.

The mouse cDNA encoding DNA topoisomerase I (TopoI) was cloned and the nucleotide sequence of 3512 bp was determined. The cDNA clone contained an open reading frame encoding a protein of 767 amino acids (aa), which is 2 aa longer than its human counterpart. Overall aa sequence homology between the mouse and human, and between the mouse and yeast (Saccharomyces cerevisiae) sequences was 96% and 42%, respectively. The mouse TopI gene was mapped at position 54.5 on chromosome 2 from linkage analyses of a three-point cross test with Geg, Ada, and a as marker genes.

3T3 Cells↗