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Biomedical subjects

T Furuta

Publications and source records attributed to T Furuta.

At least 235 records · Page 13Linked to original sources
PubMed1993

The role of macrophages in diabetic glomerulosclerosis.

To elucidate the role of macrophages in diabetic glomerulosclerosis (DGS), an immunohistologic study was performed using monoclonal antibodies to common leukocyte antigen (DAKO-LC), T cells (T3), B cells (CD22), and macrophages (MAC 387, Leu-M5, and EBM-11). Kidney biopsy specimens were obtained from 28 patients with non-insulin-dependent diabetes mellitus. Cells were identified by a three-layer immunoperoxidase technique applied to cold ethanol-fixed, paraffin-embedded sections and quantitated as the number of cells per glomerular cross-sections and number of cells per square millimeter of glomerulus. The severity of the diffuse lesions in each glomerulus was graded semiquantitatively. The average grades for all the glomeruli were calculated and registered as an index of DGS for a biopsy specimen. There was no relationship between the index of DGS and the number of T or B cells. However, the number of macrophages and common leukocyte-positive cells increased significantly in the moderate stage of glomerulosclerosis compared with the mild or advanced stage. The results suggest that macrophages may transiently infiltrate during the moderate stage of diffuse DGS, contributing to irreversible structural damage.

Adult↗
PubMed1993

Long-term effects of cografts of pretransected peripheral nerve with adrenal medulla in animal models of Parkinson's disease.

Trophic factor supplementation has been reported to enhance the survivability of grafted adrenal chromaffin cells. Because the content of nerve growth factor in the distal stump of a pretransected peripheral nerve increases markedly 1 day after transection, we injected cografts of adrenal medulla with pretransected peripheral nerve into the striata of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice and performed follow-up histological and neurochemical analyses over a 12-month period. Adrenal medullary chromaffin cells cografted with pretransected peripheral nerve survived better than in adrenal grafts alone at 1, 3, and 12 months after transplantation. Host dopaminergic fiber recovery adjacent to the grafts was more prominent in mice with cografts than in mice with adrenal grafts alone at 1 and 3 months after transplantation. Twelve months after transplantation, however, there was no significant difference between the two groups of animals because of the natural recovery of intrinsic dopaminergic fibers from MPTP toxicity. Dopamine concentration in the striata of cografted mice was higher than in mice with adrenal grafts alone at 1 month after transplantation. At 3 and 12 months after transplantation, the natural recovery of dopamine concentration from MPTP toxicity was apparent in both groups of animals and no significant difference was observed between the groups. We conclude that adrenal medullary chromaffin cells can survive for at least 12 months after grafting when cografted with pretransected peripheral nerve. Cografts enhanced the recovery of the host nigrostriatal dopaminergic system up to 3 months after transplantation, but this enhancement was not apparent at 12 months because of the natural recovery of dopaminergic fibers from MPTP toxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Chemical modification of an antitumor alkaloid, 20(S)-camptothecin: E-lactone ring-modified water-soluble derivatives of 7-ethylcamptothecin.

7-Ethylcamptothecin (1d), a model which does not have any site on the A-ring for further modification was converted into water-soluble derivatives by opening the E-ring lactone. 1d was heated in N,N-dimethylenediamine to yield amide 2a, and this was then acylated to furnish 3a-q, which were soluble in water as their HCl salts. The propionyl (3b), butyryl (3c) and methylthiopropionyl (3h) derivatives showed higher activity than the sodium salt of 1d. The acyl group makes the derivatives more lipophilic, and ease of hydrolysis of amide 2a to 1d is thought to be necessary for significant activity.

Animals↗
PubMed1993

Chemical modification of antitumor alkaloids, 20(S)-camptothecin and 7-ethylcamptothecin: reaction of the E-lactone ring portion with hydrazine hydrate.

The structure of the N-amino pyridone (4a) obtained by the reaction of camptothecin (1a) with hydrazine was determined by X-ray crystallography. A mixture of 7-ethylcamptothecin (1b) and hydrazine hydrate was stirred at room temperature, and the hydrazide (2b) was isolated as its diacetate 2c. Treatment of the 17-O-acetyl amide (5a) with hydrazine gave 1b (74% yield) and the N-amino lactam 6 (11% yield). Compounds with bulky acyl groups, 5c--e, gave 6 in modest yields. The N-amino lactam 6 was smoothly dehydrated into the pyridone 4d by refluxing in hydrazine hydrate.

Animals↗
PubMed1993

Fatal spontaneous pneumocystosis in nude rats.

Spontaneously generated fatal pneumocystosis was found in a congenitally athymic nude (rnu/rnu) rat colony. Severe pulmonary pneumocystosis was seen in rnu/rnu rats, and 10(7) to 10(8) cysts per lung were detected. No histologic changes were seen nor were Pneumocystis carinii organisms detected in heterozygous rnu/+ rats. Indirect immunofluorescence revealed strong reactivity in the sera from rnu/+ rats with rat-P. carinii cysts (originated from Wistar strain), compared with mouse- or human P. carinii cysts. The cysts isolated from rnu/rnu rats reacted strongly with antirat-P. carinii rat serum in comparison with antimouse-P. carinii rabbit serum and serum from a human with pneumocystosis. Immunoblotting studies using rat-P. carinii antigen showed that 116-kDa antigen reacted with the antirat-P. carinii serum and sera from rnu/+ rats but not with the antimouse-P. carinii serum and the serum from a human with pneumocystosis, whereas 52-kDa antigens of rat-P. carinii were recognized by all the anti-P. carinii sera tested. On the basis of our findings, the outbreak was caused by the P. carinii indigenous to the rat.

Animals↗
PubMed1993

Multistep, multicentric, and simultaneous development of hepatocellular carcinoma.

We resected a multiple hepatocellular carcinoma (HCC) which contained portal tracts, showed evidence of an early multistep condition, and a multicentric development of HCC which progressed simultaneously. A preoperative working examination revealed a tumor in S5 of the liver, which was 2.5 cm in diameter. In addition, a "nodule-in-nodule" appearance was seen on the ultrasonographic imaging. At intraoperative ultrasonography, an additional two HCCs were detected. At histologic examination of the resected specimen, the main nodule showed a nodule-in-nodule appearance. In the outer nodule, there was a well-differentiated HCC, while the portal tracts remained. The less-differentiated HCC grew in the inner nodule and was replacing the well-differentiated HCC in the outer nodule. These findings suggests morphological transition in the early stages of the multistep development of HCC. Two additional tumors (1.1 cm and 1.0 cm in diameter) detected at intraoperative ultrasonography proved to be HCCs (grade I) with marked fatty change, and with portal tracts remaining within both the HCCs. Furthermore, both of the HCCs retained their preexisting liver structure. These histologic findings coincided with the characteristics of the early stage HCC, whereas the coexistence of early stage HCCs suggests the multicentric development of HCC. Distortion, compression, and invasion of the portal tracts may appear as the tumor grows, thereby evoking an increasing risk of metastasis via the portal tracts. Therefore, the early diagnosis and treatment of HCC before the portal tracts disappear, when 1.5 cm in size or less, may be very important for surgeons and diagnosticians, as an effective curative resection may be feasible.

Carcinoma, Hepatocellular↗
PubMed1993

[Adhesion ultrastructures of mononuclear cells in experimentally-induced silicotic granuloma].

Experimental silicosis was induced by intratracheal infusions of 1 ml saline containing 50 mg standard silica (less than 5 microns diameter) in Sprague-Dawley rats. The lung tissues were observed histologically and ultrastructurally from half an hour up to 4 months. Macrophages, neutrophils, desquamated cells and their debris piled up around the alveolar ducts where the central cores of silicotic granuloma appeared. The granuloma became apparent by day 4 after the infusion and were covered by type II alveolar epithelial cells and bronchiolar cuboidal epithelial cells. Macrophages, fibroblasts and epithelial cells began to react to the antibody against proliferating cell nuclear antigen (PCNA) indicating self-replication on day 1. Macrophages in the granuloma made a close interdigitation with adjacent macrophages, and they gradually formed subplasmalemmal linear densities (SPLD) as paired forms between adjacent plasma membranes, and unpaired forms facing the interstitial matrix. SPLD were composed of linear densities with actin-like microfilaments along the leaflets of plasma membrane and were associated with extracellular dense bands which resembled a limited length of basement membrane. Interdigitation and SPLD structures were quite rare on day 1, but the number of macrophages with both structures increasingly appeared. The frequency of SPLD in macrophages also increased on a time course of granuloma maturation up to 4 months. Thus SPLD, which were originally found in the mononuclear phagocytes including macrophages, epithelioid cells and multi-nucleated giant cells, particularly in immune granuloma of man, also played a basic role in immobilizing macrophages in lesions of silica-induced granulomas.

Animals↗
PubMed1993

[A case of early gastric cancer with Virchow's node metastasis, effectively treated by high dose of UFT].

We report a case of early gastric cancer with Virchow's node metastasis. The patient underwent partial gastrectomy and postoperative immunochemotherapy using MMC, 5'-DFUR and PSK, which reduced the Virchow's node. Three years after surgery, we found metastases to the left subclavicular and axillary nodes other than the Virchow's node. Then UFT was administered orally at 600 mg/day, and the metastatic nodes diminished, then vanished. The patient is alive nearly five years after surgery.

Adenocarcinoma↗
PubMed1993

[Two cases of metastatic brain tumor treated by interstitial brachytherapy].

The prognosis of patients with metastatic brain tumor is very poor. Median survival of these patients has ranged from 1 month with no therapy, to 2 months with steroid, and from 3 to 6 months with brain radiation therapy of the whole brain. A more recent study comparing radiation therapy alone with surgery plus radiation, has shown good results in the combined surgery and radiation therapy group. But surgical excision is usually limited to patients with a surgically accessible solitary metastasis. And therapeutic options are limited once the tumor recurs locally after whole brain irradiation. Interstitial irradiation allows the delivery of a high dose of localized irradiation in the area of tumor recurrence with minimal risk of radiation damage to the surrounding brain tissue. But brachytherapy for brain metastasis has been performed in few cases. We reported two patients with unresectable metastatic brain tumors who were successfully treated with iridium-192 interstitial brachytherapy, and we discuss the strategy of the treatment. Case 1: A 78 year-old-man underwent a total gastrectomy for gastric cancer. Five months after surgery, he developed right hemiparesis. CT scan revealed a left occipital tumor with massive brain edema and a tiny nodule of tumor in the left thalamic region. The primary site was well-controlled and no systemic disease was seen during subsequent whole body examination. The occipital lesion was surgically excised and he received a postoperative radiation therapy of 50 Gy to the whole brain. The thalamic tumor had not responded to the irradiation and the size of tumor rapidly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1993

[Immunological effects of locoregional immunochemotherapy for liver metastases of gastric cancer].

Nine gastric cancer patients with simultaneous liver metastases were given intermittent transarterial administration of chemotherapeutics (adriamycin, mitomycin C or 5-fluorouracil) and biological response modifiers (BRM; OK-432 and interleukin (IL) -2) after gastrectomy. In terms of direct antitumor effect on liver metastases, a partial response was observed in 4 of 9 cases (44%). In addition, the concentration of 3 kinds of cytokines such as IL-6, tumor necrosis factor (TNF) -alpha and interferon (IFN) -gamma in the peripheral blood sera was measured immediately before and after transarterial administration of agents. While the concentration of IL-6 increased by BRM, chemotherapeutics could not alter the level of IL-6. As for TNF-alpha and IFN-gamma, no particular changing pattern was observed after transarterial administration. Furthermore, natural killer (NK) activity of peripheral blood mononuclear cells was measured. Administration of either BRM or BRM in combination with chemotherapeutics caused a decrease in NK activity, whereas chemotherapeutics did not. Flow cytometric analysis using 3 kinds of monoclonal antibodies (Anti-CD16, CD56 and CD57) revealed that the proportion of subset of both highly activated NK cells (CD16+.CD56+.CD57-) and moderately activated NK cells (CD16+.CD56+.CD57+) reduced after administration of BRM.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[A case of glial microtumor treated with brachytherapy using MRI guided stereotactic system].

A 34 year old male suffered from convulsion on his right side with loss of consciousness. Neither plain nor enhanced CT could clearly demonstrate a lesion. However, a Gd-DTPA enhanced T1 weighted image (T1WI) demonstrated an enhancing lesion (2 cm in diameter) in the left frontal lobe including the motor cortex. This lesion was not identified on plain T1WI. A T2 weighted image (T2WI) showed a high intensity lesion without mass effect slightly larger than the enhanced area on T1WI. This lesion was suspected to be a glial microtumor, but, because it was difficult to differentiate it from a cerebral infarction, it was confirmed to be a neoplasm by means of an MRI guided stereotactic biopsy. The histological diagnosis of the frozen section was a grade 2 astrocytoma. Subsequently brachytherapy with 192Ir seeds was performed, and about 80Gy of interstitial irradiation was given to the edge of the enhanced area on MRI. The minimum dose in the high intensity area on T2WI was about 50Gy. The patient was discharged with no neurological deficits. The Gd-DTPA enhanced lesion decreased in size six months after the treatment. MRI guided stereotactic system makes it possible to target a high intensity lesion on T2WI in brachytherapy. Brachytherapy using this system is considered to be useful in the treatment of glial microtumor in an area in which it is difficult to identify it on CT.

Adult↗
PubMed1993

[A case of secondary leukemia induced by chemotherapy with a CDDP-based regimen for gastric cancer 5 years following radical resection].

Cisplatin, mitomycin C and 5-fluorouracil were given a 55-year-old woman for an unresectable gastric cancer, and successful radical gastrectomy was performed. Postoperative adjuvant immunochemotherapy using UFT and PSK was continued for about 4 years and 4 months. Pancytopenia was observed at 5 years after the treatment and then marked leucocytosis was noted. She also showed complications of general fatigue, appetite loss etc. A secondary acute leukemia associated with eosinophilia was diagnosed by peripheral blood examinations, showing WBC, 122,400: blast, 37.5 % and eosinophil, 41%. Results also showed atypia and pseudo-Pelger nuclear abnormality of eosinophil, high positive stain of cell myelogenic cell surface marker, many numeral and structural abnormalities of chromosomal analysis, etc. From the above results, it was suggested that the leukemia might be induced by previously performed chemotherapy. The patient died about 2 months following its onset.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Stable isotope dilution mass spectrometry for the simultaneous determination of cortisol, cortisone, prednisolone and prednisone in plasma.

A capillary gas chromatographic-mass spectrometric method for the simultaneous determination of cortisol, cortisone, prednisolone and prednisone in human plasma is described. [1,1,19,19,19-2H5]Cortisol, [1,1,19,19,19-2H5]cortisone, [1,19,19,19-2H4]prednisolone and [1,19,19,19-2H4]prednisone were used as internal standards. Formation of the bismethylenedioxy-3-heptafluoro-n-butyryl (BMD-HFB) derivatives made possible the separation of the four corticosteroids with good gas chromatographic behaviour. The new double derivatization has been demonstrated to be of value for sensitive and selective quantification by this technique. Detection was performed by monitoring the molecular ion (M+) of the BMD-HFB derivatives for cortisone and prednisolone, the [M - 18]+ ion for cortisol, and the [M - 30]+ ion for prednisone. The method requires no complex corrections for contributions and provides good accuracy and precision.

Cortisone↗
PubMed1992

Reversible stepwise mechanism involving a carbanion intermediate in the elimination of ammonia from L-histidine catalyzed by histidine ammonia-lyase.

L-Histidine labeled with deuterium at the C-5' position of the imidazole ring, L-[5'-2H]histidine (His-5'-D), was used as a probe for investigating a stepwise reversible mechanism via a carbanion intermediate in the elimination of ammonia catalyzed by histidine ammonia-lyase (EC 4.3.1.3). The labeled L-histidine (His-5'-D) (2.45 mM) was incubated with histidine ammonia-lyase (200 units) from Pseudomonas fluorescens at pH 7.0 or 9.0 at 25.0 degrees C for 24 h. The time course of the reaction was examined to determine the rates of enzyme-catalyzed hydrogen exchange at C-5' of L-histidine and urocanic acid. The finding of the enzyme-catalyzed hydrogen exchange at C-5' of both L-histidine and urocanic acid in the presence of L-histidine provided a rational explanation for a stepwise reversible mechanism via a carbanion intermediate in the elimination reaction. The rate of increase in the concentration of urocanic acid exchanged with hydrogen (UA-5'-H) did not depend on the formation rate of urocanic acid and UA-5'-H was continuously formed at a constant rate (25.6 microM/h) even after the completion of urocanic acid formation. These observations suggested the presence of the reversible reaction of urocanic acid and a carbanion intermediate. Since there was only a minor contribution for the formation of UA-5'-H from L-histidine exchanged with solvent hydrogen (His-5'-H), the main pathway in the enzymatic reaction of His-5'-D must be the formation of UA-5'-D via a carbanion intermediate (carbanion-D). Regeneration of the carbanion-D from UA-5'-D by its reverse reaction and subsequent hydrogen incorporation at C-5' would contribute to a large extent for the formation of UA-5'-H. The stability of carbanion was also demonstrated to be approximately three times higher at pH 7.0 than at pH 9.0.

Ammonia↗
PubMed1992

Simultaneous determination of stable isotopically labelled L-histidine and urocanic acid in human plasma by stable isotope dilution mass spectrometry.

A capillary gas chromatographic-mass spectrometric method for the simultaneous determination of stable isotopically labelled L-histidine (L-[3,3-2H2,1',3'-15N2]histidine, L-His-[M + 4]) and urocanic acid ([3-2H,1',3'-15N2]urocanic acid, UA-[M + 3]) in human plasma was developed using DL-[2,3,3,5'-2H4,2'-13C,1',3'-15N2]histidine (DL-His-[M + 7]) and [2,3,5'-2H3,2'-13C,1',3'-15N2]urocanic acid (UA-[M + 6]) as internal standards. L-Histidine and urocanic acid were derivatized to alpha N-(trifluoroacetyl)-imN-(ethoxycarbonyl)-L-histidine n-butyl ester and imN-(ethoxycarbonyl)urocanic acid n-butyl ester. Quantification was carried out by selected ion monitoring of the molecular ions of the respective derivatives of L-His-[M + 4], DL-His-[M + 7], UA-[M + 3] and UA-[M + 6]. The sensitivity, specificity, precision and accuracy of the method were demonstrated to be satisfactory for measuring plasma concentrations of L-His-[M + 4] and UA-[M + 3] following administration of trace amounts of L-His-[M + 4] to humans.

Gas Chromatography-Mass Spectrometry↗
PubMed1992

Simultaneous determination of cortisol and cortisone in human plasma by stable-isotope dilution mass spectrometry.

A method for the simultaneous determination of cortisol and cortisone in human plasma was developed using capillary gas chromatography-mass spectrometry-selected ion monitoring. [2H5]Cortisol and [2H5]cortisone were used as internal standards. Cortisol and cortisone in plasma were determined from the peak-height ratios of the [M-31] fragment ions of the methoxime-trimethylsilyl derivatives of cortisol and [2H5]cortisol (m/z 605 and 610) and of cortisone and [2H5]cortisone (m/z 531 and 536). Sensitivity, specificity, precision, accuracy and reproducibility of the method were demonstrated to be satisfactory for measuring the circulating concentrations of cortisol and cortisone.

Cortisone↗