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Biomedical subjects

Y Akagi

Publications and source records attributed to Y Akagi.

At least 73 records · Page 4Linked to original sources
PubMed1997

TCV-116 inhibits interstitial fibrosis and HSP47 mRNA in rat obstructive nephropathy.

Unilateral ureteral obstruction (UUO) is a well established disease model leading to fibrosis of the obstructed kidney. In this model, involvement of enhanced renin-angiotensin system in the pathogenesis of interstitial fibrosis has been demonstrated. A 47-kDa heat-shock protein (HSP47) was originally identified as a collagen-binding stress protein, and is currently considered to be a collagen-specific molecular chaperone that plays a pivotal role during the biosynthesis and secretion of procollagen from endoplasmic reticulum. To test if HSP47 is involved in interstitial fibrosis in UUO, we examined the expression of HSP47 mRNA in rat UUO kidneys after 12 hours. 1, 4, 7 days of obstruction. HSP47 mRNA expression was significantly increased as early as 12 hours after obstruction and was sustained at the increased level until seven days. Type I collagen mRNA significantly increased after four days of UUO. Fibrotic changes of interstitium appeared in Masson's trichrome stained section after four days. To explore the possible involvement of angiotensin II (Ang II) in HSP47 induction, the effect of Ang II receptor antagonist (TCV-116) and angiotensin converting enzyme inhibitor (lisinopril) was tested. TCV-116 or lisinopril was given to the animals orally once a day at the dose of 10 mg/kg. TCV-116 or lisinopril significantly ameliorated the fibrotic change of interstitium seven days after obstruction. HSP47 and type I collagen mRNA levels in the TCV-116- or lisinopril-treated groups were reduced to about 60% of untreated UUO. A possible involvement of HSP47 in the pathogenesis of interstitial fibrosis in UUO is suggested; however, further investigation is required to identify the signals involved in the induction of HSP47 in UUO.

Angiotensin II↗
PubMed1996

An analysis of mandibular bone complications in radiotherapy for T1 and T2 carcinoma of the oral tongue.

PURPOSE: To examine the incidence of mandibular bone complication in patients who underwent radiotherapy for T1 and T2 carcinomas of the oral tongue and to analyze the factors contributing to its occurrence. METHODS AND MATERIALS: The clinical records of 148 patients with T1 and T2 carcinoma of the oral tongue treated with radiotherapy alone between 1978 and 1989 were examined retrospectively. Interstitial brachytherapy, used as the major treatment modality, was performed using cobalt needles, radium needles, or iridium hairpins. The prescribed dose at the plane 5 mm from the plane of the radioactive sources was 65-70 Gy in interstitial brachytherapy alone, and 50-60 Gy in the combined treatment with external irradiation. An external irradiation dose of 30 Gy was usually used. RESULTS: Eleven of the patients showed radiation-induced mandibular bone complication. Two (1 T1, 1 T2) had been treated with interstitial brachytherapy alone, and nine (2 T1, 7 T2) with the combination of external irradiation and interstitial brachytherapy. The incidence of radiation complication of bone was significantly higher in the patients with T2 tumors (p = 0.04) and in those who received the combined treatment (p < 0.01). Multivariate analysis revealed that the total dose (p = 0.04) and dose rate of interstitial brachytherapy (p = 0.03) were significant factors contributing to radiation bone complication. A significant difference in the incidence of bone complication was also seen between patients who received a total dose of 90 Gy or more and those who received less than 90 Gy (p < 0.01), as well as between patients who were treated with 0.55 Gy/h or higher and those who were treated with less than 0.55 Gy/h (p = 0.03). CONCLUSION: A significant increase in the incidence of bone complication was found at the total dose of 90 Gy or more and at the dose rate of 0.55 Gy/h or higher. In combined treatment with external irradiation and interstitial brachytherapy, the interstitial brachytherapy dose of 60 Gy appears to be the threshold at which mandibular bone complication is induced when the external irradiation dose is 30 Gy.

Adult↗
PubMed1996

Inhibition of TGF-beta 1 expression by antisense oligonucleotides suppressed extracellular matrix accumulation in experimental glomerulonephritis.

Overproduction of transforming growth factor-beta 1 (TGF-beta 1) has been implicated in the pathogenesis of fibrotic diseases. TGF-beta 1 plays a crucial role in the accumulation of extracellular matrix (ECM) in human and experimental glomerular diseases. However, it remains unclear whether inhibition of TGF-beta 1 overproduction would suppress TGF-beta 1-induced ECM accumulation. To inhibit the overproduction of TGF-beta 1 in experimental glomerulonephritis induced by anti-Thy 1.1 antibody, we introduced antisense oligodeoxynucleotides (ODN) for TGF-beta 1 into the nephritic kidney by the HVJ-liposome-mediated gene transfer method. Sense, scrambled or reverse ODN were also introduced as controls. Transfected ODN accumulated mainly in the nuclei of mesangial cells in the glomeruli of transfected kidneys. In the antisense ODN-transfected rats, a marked decrease in expression of TGF-beta 1 mRNA was confirmed by Northern analysis. Consequently, the expression of TGF-beta 1 protein in the glomerulus was markedly reduced in the antisense ODN-transfected kidney with a comparable effect in preventing glomerular ECM expansion in experimental glomerulonephritis. In contrast, sense, scrambled and reverse ODNs failed to suppress TGF-beta 1 expression and ECM accumulation. Thus, these results suggested that inhibition of TGF-beta 1 overproduction could suppress progression to glomerulosclerosis.

Animals↗
PubMed1996

Hepatic arterial chemotherapy for liver metastases from colorectal cancer.

We have investigated the complications, toxicities, tumor response and survival rate with hepatic arterial (HA) chemotherapy for liver metastases from colorectal cancer. Forty-three patients with measurable liver metastases and 10 patients after the resection of liver metastases were treated with HA bolus mitomycin C (MMC) or continuous fluorouracil (5-FU) infusion between 1986 and 1994. The catheter- or reservoir-related complications such as catheter induced infection, subcutaneous reservoir pocket infection, or catheter or hepatic artery occlusion occurred in 14 patients (26%) mainly in our early cases. Severe gastritis or a gastroduodenal ulcer developed in 12 patients (23%), in particular after treatment with continuous infusion of 5-FU and when the catheter was placed into the gastroduodenal artery during laparotomy. An ulcer often caused a serious complication such as a duodeno-biliary fistula, penetration into the hepatic artery or duodenal perforation. Also noted were upper gastrointestinal symptoms in 26 patients, hepatic toxicities in 3 patients, and bone marrow depression in 4 patients. Because of these complications and toxicities, HA therapy was discontinued in more than 60% of the cases. The overall tumor response rate was 17%. However, in the cases which were treated by 5-FU continuous infusion for longer than 3 months, the response rate was higher than 60%. There was no significant difference in survival rate between HA therapy and systemic palliative chemotherapy. These results suggest that it is important to prevent gastrointestinal toxicities in order to allow continuation of HA continuous 5-FU infusion therapy which could provide a higher response rate and a better survival for colorectal cancer patients with liver metastases.

Colorectal Neoplasms↗
PubMed1996

[Analysis of cyclin dependent kinase inhibitors, p16INK4a and p15INK4b gene, in acute lymphoblastic leukemias].

We examined the abnormality of p16INK4a and p15INK4b genes in 14 cases of human acute lymphoblastic leukemias (L1; 8 sample from 6 cases, L2; 10 samples from 7 cases, L3; 1 sample from 1 case) using DNA from bone marrow cells. The frequency of homozygous deletion of p16INK4a was 21.4% (3/14) and that of p15INK4b was 7.1% (1/14) and both genes were deleted in 7.1% (1/14) according to Southern blot and PCR analysis. The deletion of p16INK4a and/or p15INK4b was detected in 50% (3/6) of L1, 28.6% (2/7) of L2. The frequency of deletion was 33.3% (3/9) of B cell origin, 66.7% (2/3) of T cell origin and 0% (0/2) of nonBnonT cell origin. By PCR-SSCP analysis on exon 1 and exon 2 of p16INK4a and p15INK4b genes, we detected one case of unusual migrated band in L1 B cell origin. The base substitution, C to G, located in intron 1 of p15INK4b, 9 base upstream of intron 1-exon 2 boundary, was determined by DNA sequencing analysis. Deletion of p16INK4a and/or p15INK4b gene may contribute to etiology of ALL.

Adolescent↗
PubMed1996

[Histological observation of anterior capsular edges produced by continuous curvilinear and diathermy capsulorhexis].

Radiofrequency endodiathermy capsulorhexis (DC) is a new method for anterior capsulorhexis in cataract surgery. DC may confer some advantages over continuous curvilinear capsulorhexis(CCC) in certain clinical situations. The elasticity of capsulorhexis produced by DC and the proper diathermy time are still unclear. Histological examination of rabbit lenses, on which a variety of coagulation times (0.5 to 5.0 sec) were tested revealed that 0.5 sec was long enough to coagulate the anterior capsule and that the longer coagulation extend the tissue damage into the deeper cortex. Small capsulorhexis (3.5 mm in diameter) produced experimentally with DC showed less elasticity than that produced with CCC when the edge of the capsulorhexis was pulled. Thus the heat coagulation of the capsular edge produced by DC results in less elasticity than that produced by CCC.

Animals↗
PubMed1995

In vivo transfection of genes for renin and angiotensinogen into the glomerular cells induced phenotypic change of the mesangial cells and glomerular sclerosis.

Locally activated renin angiotensin system plays an important role in the progression of the glomerular diseases. In order to understand the local effect of overexpressed angiotensin II in the glomerulus in situ, we introduced human genes for renin and angiotensinogen into the rat kidney by hemagglutinating virus of Japan-liposome procedure. Three days after transfection human renin was detected in the glomeruli by immunohistochemistry. Seven days after transfection, extracellular matrix was expanded in the glomeruli and alpha-smooth muscle actin was expressed in the mesangial cells. These results suggest that locally activated renin angiotensin system induces glomerular sclerosis and a phenotypic change in mesangial cells.

Actins↗
PubMed1995

Expression of transmembrane-type protein tyrosine phosphatase mRNA along rat nephron segments.

Protein phosphorylation on tyrosine residues is one of the main cell signaling mechanisms. Cellular phosphotyrosyl levels are regulated by the activities of protein tyrosine kinases (PTK) and protein tyrosine phosphatases (PTPase). We have previously reported cDNA cloning of several types of PTPase from rat kidney, including LRP (leukocyte common antigen-related protein; also known as the transmembrane-type tyrosine phosphatase, i.e., RPTP alpha). LRP mRNA was shown to be abundant in the kidney; however, our understanding of the functional role of LRP in the kidney is very limited. To gain keener insight into the function of LRP in the kidney, our first approach was to reveal its mRNA distribution along rat nephron segments. Large signals were found in inner medulla by Northern blot analysis. By using a reverse transcription and polymerase chain reaction assay of individual microdissected tubule segments along the nephron [proximal convoluted tubule (PCT), medullary thick ascending limb (MTAL), cortical collecting duct (CCD), outer medullary collecting duct (OMCD), and inner medullary collecting duct (IMCD)] and glomeruli, we revealed intrarenal localization of LRP mRNA. LRP mRNA was detected in all nephron segments tested but was relatively rich in the IMCD. Rank order of the signal intensity was IMCD > PCT = OMCD > CCD > MTAL = glomeruli. Immunohistochemistry also revealed that LRP was abundant in IMCD. This pattern of expression gives rise to an interesting possibility that LRP might be involved in the specific renal tubule function, such as urinary concentrating mechanism; however, further study is required to describe the function of LRP in more detail.

Amino Acid Sequence↗
PubMed1995

Biphasic immune responses of cats under controlled infection with a feline enteric coronavirus-79-1683 strain.

Kittens inoculated orally with 10(2) PFU of feline enteric coronavirus developed no antibody to the virus despite the repeated challenges. However, they developed antibody for a long period with 5 x 10(3)-1.6 x 10(5) (mean 3 x 10(4)) and with 2.5 x 10(3)-2 x 10(4) (mean 6 x 10(3)) immunoperoxidase antibody titer when they were challenged with 10(5) and 10(3) PFU of virus following previous challenges, respectively. Viremia was found when kittens were inoculated with 10(5) PFU of virus, but not with 10(3) PFU of virus. The dose of 10(3) PFU of virus seemed to be a lower limit to establish infection. These results indicate that local infection induces a low antibody response and systemic infection induces a high antibody response.

Animals↗
PubMed1995

Total pelvic exenteration for locally advanced colorectal carcinoma--postoperative complications.

This study was designed to clarify the postoperative major complications of total pelvic exenteration for locally advanced colorectal cancer. Twenty-six patients (primary disease: 17, recurrent disease: 9) were retrospectively studied. Major complications developed in 30.8% (8 of 26); in 23.5% (4 of 17) for a primary disease and in 44.4% (4 of 9) for a recurrent disease. Only 2 patients (7.7%) died within 30 days after the operation; one patient died of hepatic failure and another of pelvic sepsis. Postoperative ileus developed at a high rate of 11.5% (3 of 26). Ileo-ileal anastomotic leakage developed at a rate of 7.7% (2 of 26) and it commonly occurred following irradiation. The remaining one patient had gastrointestinal bleeding. These 6 patients surviving the operation were successfully managed conservatively. Conclusion was as follows: Total pelvic exenteration should be performed carefully and aggressively regardless of the development of postoperative complications.

Adult↗
PubMed1995

[Cell kinetics of rat lens epithelium by cytofluorometric nuclear DNA determination].

The cell kinetics of rat lens epithelium was assessed by measuring the changes in the nuclear DNA contents during sugar cataract formation. Six-and-12-week-old Sprague-Dawley male rats were used and divided into the following groups: fed on normal chow, fed on 25% galactose diet, and fed on normal chow after 5 days on the 25% galactose diet. Every second day following the beginning of each chow feeding, lenses were extracted, and lens capsules with epithelial cells were obtained. After a few day's fixation in 4% paraformaldehyde dissolved in 0.1M phosphate buffer (pH 7.4), DAPI (4'6-diamidino-2-phenylindole)-stained lens epithelial cells were measured by fluorescence cytophotometry. The epithelia in the normal chow-fed rats contained many 2C and a few 4C nuclei. In the 25% galactose-fed rats, 4C nuclei increased gradually in number until the fifth day, and then decreases slowly day by day. Abnormal polyploid nuclei (8C) were observed in the 25% galactose-fed rats. 4C nuclei decreased rapidly after the diet reversal. These results indicate that galactose feeding caused higher DNA synthesis of rat lens epithelial cells and a higher possibility of abnormal cell division.

Animals↗
PubMed1995

[Role of pharmacist in cancer pain management].

It is essential for patients to have understanding of the significance of morphine administration and to cope well with its side effects, as it leads to enhancement of the analgesic effects of morphine in the treatment of cancer pain. Since August 1993 we have used the booklet "Relieving Pain Effectively--Manual for Patients" and have consulted up to date approximately 670 patients about taking narcotics. The initial information eliminates the anxiety before taking morphine--we set up the time that each patient should take medicine to fit their life-style and explain about the the medicine and its side-effects. For this reason, the above information takes approximately 30 to 60 minutes per patient. We guide the patient over to over till the pain and side-effects have disappeared and file a "Morphine Education Record" with the details. We also prepare a "Pain and Side-Effect Control Sheet" that consists of 6 items and a pain scale where 0 equals no pain and no side-effect and 5 equals most pain and side-effects. Patients select the scale themselves every day. Pharmacists provide the information to a doctor and advise him on steps against side-effects, selection of dose, interval and rescue-dose. This is a report on the role of the pharmacist in patient narcotics guideline for cancer pain management.

Humans↗
PubMed1994

Primary linitis plastica carcinoma of the colon and rectum.

BACKGROUND: Linitis plastica carcinoma (LPC) usually shows a scirrhous growth pattern with a severe stromal desmoplastic reaction. Another growth pattern showing lymphangiosis carcinomatosa rather than scirrhous growth pattern, however, was noted. This study was designed to clarify the clinical and pathologic characteristics of colorectal LPC. METHODS: Linitis plastica carcinoma was reviewed clinicopathologically and classified into two types according to the histologic growth pattern: The first was a scirrhous type (nine patients) and the second, a lymphangiosis type (three patients). RESULTS: Grossly, the mucosal surface of the scirrhous type had a granular, cobblestone, gyriform-like appearance. The cancer cells were composed mainly of poorly differentiated or signet-ring cells and were accompanied by a severe stromal desmoplastic reaction; lymphatic permeation was not so marked. Most patients with this type of cancer died of peritonitis carcinomatosa. The mucosal surface of the lymphangiosis carcinomatosa had a smooth and glossy appearance. The cancer cells were composed mainly of moderately differentiated cells, frequently with a glandular formation. Stromal desmoplastic reaction was not so marked. The growth pattern was characterized by lymphangiosis carcinomatosa and marked venous invasion. All patients who had this type died of distant metastases. CONCLUSION: Perhaps with earlier diagnosis and aggressive treatment, the peritoneal dissemination of scirrhous LPC and distant metastasis of lymphangiosis LPC may be minimized.

Adenocarcinoma, Scirrhous↗
PubMed1994

Dose-reducing effect of Lipowitz metal-embedded spacers in interstitial brachytherapy for carcinoma of the mobile tongue.

Dose-reducing effects of spacers with and without a Lipowitz metal plate for the purpose of decreasing osteoradionecrosis after interstitial brachytherapy for tongue cancers were examined experimentally and clinically. The thicker the sample or spacer and the thicker the metal plate, the greater was the dose reduction achieved. A more marked dose reduction was achieved with iridium than with radium because of lower gamma ray energy of iridium. Iridium has been used widely as a radioactive source for interstitial brachytherapy. It was concluded therefore that a metal plate should be used as a shield into the spacer in interstitial brachytherapy both to reduce the radiation dose to surrounding normal tissues and to help prevent osteoradionecrosis.

Alloys↗
PubMed1993

[Apoptosis in radiosensitive malignant tumors].

This study reported the radiation induced apoptosis in 6 cases with malignancies that were observed rapid tumor regression with radiotherapy up to 10 Gy. Microscopic examinations of 6 cases revealed the tumor cell number reduction and the appearance of apoptotic cells in the irradiated cases. It is suggested that the radiation-induced apoptosis plays an important role in rapid tumor regression by radiotherapy and occurs not only in lymphoma which has been recently reported in vitro but also in carcinoma.

Apoptosis↗
PubMed1993

Experimental and clinical studies on dose reduction effects of spacers in interstitial brachytherapy for carcinoma of the mobile tongue.

The difference of radiation dose reduction effect with spacers of different materials, a heat-curing denture base resin and a silicon impression material, was examined experimentally and clinically. Radium needles and iridium hairpins were used as radioactive sources. In both studies, it was revealed that a dose reduction effect of silicon impression material was greater than that of denture base resin. Silicon impression material was thought to be a better material for spacers because of its larger radiation dose reduction effect and the time saving to produce the spacer.

Brachytherapy↗
PubMed1993

Radiation-induced apoptosis and necrosis in Molt-4 cells: a study of dose-effect relationships and their modification.

Cell death induced by various radiation doses in Molt-4 and L5178Y cells was studied. Molt-4 cells have a low threshold for induction of interphase death while L5178Y cells have a high threshold. Interphase death in Molt-4 cells at doses > 100 Gy and in L5178Y cells at doses > 300 Gy showed typical necrosis. In contrast, cell death in Molt-4 cells after 2-30 Gy had features of both apoptosis and necrosis; the appearance of orcein-stained cells in the light microscope was suggestive of apoptosis, showing chromatin margination and apoptotic bodies. The concomitant appearance of non-viable cells as estimated by either orcein staining or eosin dye staining correlated well with this. Early cell swelling and a diffuse smear pattern in DNA gel electrophoresis were however suggestive of necrosis. Detailed electron microscopic observations revealed that events leading to the interphase death of Molt-4 cells after 2-30 Gy involved complicated pathways which included both apoptotic changes in the nucleus and necrotic changes in the cytoplasm. TPA not only had a protective effect on the interphase death of Molt-4 cells, but also converted the mode of cell death from interphase death to mitotic death after low doses of radiation. Cycloheximide and H-7, known to inhibit apoptosis in irradiated thymocytes, had no protective effect on the interphase death of Molt-4 cells, suggesting that the events leading to interphase death in Molt-4 cells might be different from those in thymocytes. BrdUrd-labelling had a sensitizing effect on the radiation response, but no effect on interphase death in Molt-4 cells thus suggesting that DNA damage may not be responsible for interphase death.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗