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Biomedical subjects

H Kakinuma

Publications and source records attributed to H Kakinuma.

At least 55 records · Page 3Linked to original sources

Transglucosylation with 6'-chloro-6'-deoxysucrose and immobilized isomaltulose-producing microorganisms using 2,2-dimethyl-1,3-dioxolane-4-methanol and its related compounds as acceptors. Steric and chemical requirement of the glucosyl acceptor.

Enantioselective and diastereoselective alpha-D-glucosylation of 2,3-O-isopropylidene-erythritol was observed in transglucosylation with a synthetic donor using three kinds of immobilized isomaltulose-producing microorganisms. Several related compounds, including an 2,3-O-isopropylidenated aldotetrose dimethyl dithioacetal and an aldotetronic acid ester were also glucosylated in moderate or good yield, depending on the microorganism utilized. Steric as well as functional group factors are discussed in relation to the substrate specificity of the glucosyl acceptor.

Carbohydrate Conformation↗

Enhanced suppression of tumor growth by combination of angiogenesis inhibitor O-(chloroacetyl-carbamoyl)fumagillol (TNP-470) and cytotoxic agents in mice.

The antitumor effect of the novel angiogenesis inhibitor O-(Chloroacetyl-carbamoyl) fumagillol, TNP-470 (TNP, s.c.), a synthetic analogue of fumagillin, was studied in combination with cytotoxic agents--mitomycin C (MMC, i.p.), Adriamycin (i.p.), cisplatin (i.p.), and 5-fluorouracil (i.p.), using B16BL6 melanoma (B16 M) and Lewis lung carcinoma in C57BL/6 mice. When the mice were treated on days 3 and 5, addition of MMC (total dose, 5 mg/kg) or 5-fluorouracil (140 mg/kg) to TNP (150 mg/kg) maximally reduced s.c. B16 M volume from 60 to 15% or from 68 to 40% of control, respectively, and addition of MMC (5 mg/kg) to TNP (150 mg/kg) reduced s.c. Lewis lung carcinoma volume from 75 to 62% of control (P < 0.02, compared to the corresponding single drug treatments). During treatment on days 3, 5, 7, 9, and 11, addition of MMC (5 mg/kg) to TNP (150 mg/kg) reduced s.c. B16 M volume from 43 to 6% of control and reduced the number of pulmonary metastasis of i.v. B16 M from 26 to 5% of control (P < 0.001). For established tumors (> 5 mm in maximal diameter), addition of MMC (12-14 mg/kg), Adriamycin (15-17.5 mg/kg), or cisplatin (4 mg/kg, by one shot) to TNP (120-140 mg/kg) with a 6-7 fractionated dosing schedule reduced s.c. B16 M volume from 50 to 20, 24, or 31% of control and reduced s.c. Lewis lung carcinoma volume from 52 to 34, 27, or 34% of control, respectively (P < 0.02). The effect of combination therapy was additive and dose-dependent, and the earlier fractionated dosing schedule exerted more enhanced antitumor effects. TNP reduced the body weight by approximately 10% of control at maximum, but this toxicity was reversible and was not affected by addition of the cytotoxic agents. The results suggest that the combination of angiogenesis inhibitor TNP and standard cytotoxic agents can be a beneficial addition to the treatment of solid tumors.

Animals↗

Granulocyte colony-stimulating factor produced by bladder carcinoma of a patient with leukemoid reaction did not affect proliferation of the tumor cells.

Bladder carcinoma associated with leukemoid reaction, though it rarely occurs, is considered highly malignant and has proved to produce granulocyte colony-stimulating factor (G-CSF). Interest exists in whether G-CSF itself or G-CSF producing ability reflects the malignant potential of such a tumor, possibly through an autocrine mechanism. In a patient with invasive bladder carcinoma, we found that the tumor cells produced G-CSF responsible for a remarkable leucocytosis. However, we could not detect the rearrangement and amplification of the G-CSF gene nor the expression of G-CSF receptor in the tumor cells. Our immunohistological and molecular biological study failed to demonstrate a crucial role for G-CSF in mediating a growth advantage for the tumor.

Base Sequence↗

Three subtypes of poroid neoplasia in a single lesion: eccrine poroma, hidroacanthoma simplex, and dermal duct tumor. Histologic, histochemical, and ultrastructural findings.

A single poroid neoplasm composed of three histologically distinct lesions (hidroacanthomas simplex, eccrine poroma, and dermal duct tumor) is reported. Comparative histologic, histochemical, and electron-microscopic studies revealed that each tumor subtype contained varying proportions of poroid cells, clear cells, and cuticular cells. The major component of all three neoplasms was poroid cells, which, under the electron microscope, were characterized by a few, small, poorly developed desmosomes, and were histochemically characterized by a positive succinic dehydrogenase reaction. The dermal duct tumor was cultured, and showed similar histochemical findings to the in vivo poroid cells. These results suggest that poroid cells play the most important role in the histogenesis of these three neoplasms.

Acrospiroma↗

A case of extramammary Paget's disease with depigmented macules as the sole manifestation.

We report a 76-year-old man who had four depigmented macules in the genital area as the sole manifestation of extramammary Paget's disease (EMP). Histologically, many scattered, dissociated, plump Paget cells, and small intraepidermal nests of these cells were seen in all four lesions. The distribution of Paget cells extended beyond the margin of the depigmented areas into adjacent normally pigmented skin. Fontana-Masson staining revealed a reduction in, or absence of, melanin deposition along the basal layer of the depigmented lesions, in contrast with an abundance of melanin along the basal layer of the adjacent normal skin. Pigment-blockade melanocytes and melanophages were seen within or below the affected epidermis. The depigmentation in this case could have been caused by a symbiotic disorder between melanocytes and keratinocytes (including melanocyte destruction), and by a disorder in melanosome transmission to the keratinocytes. This case illustrates that a depigmented macule may be a diagnostic feature of EMP. Moreover, depigmentation is probably one of the earliest clinical features of EMP, and not a neighbouring secondary change such as occurs in the Sutton's halo naevus phenomenon.

Aged↗

Radionuclide evaluation of the uretero-ileoceco-proctostomy (ileocecal rectal bladder).

Technetium 99m diethylenetriaminepentaacetic acid renoscintigraphy was applied to 14 patients to obtain comprehensive information on the kidney and urinary tract 12.6 +/- 8.8 months (mean +/- SD) after uretero-ileoceco-proctostomy (ileocecal rectal bladder) diversion. The total glomerular filtration rate (GFR) was within the normal range in all patients, and the diuretic renogram was normal in 19 of 28 kidneys, dilated-nonobstructive in 7 and obstructive-intermediate in 2. The mean colonic reflux was 16.6 +/- 18.4% of total excretion and the mean total residual in the colon and rectum was 38.8 +/- 15.5%. In the second study, performed 12.4 +/- 3.5 months later in 9 patients, the GFR of bilateral and individual kidneys remained stable, 17 of 18 kidneys were normal as judged by both renography and pyelography, and the occurrence and degree of colonic reflux decreased. There was a tendency for the rectal capacity to increase, while the total residual tended to decrease solely due to the decrease in colonic residual. These results indicate that the ileocecal rectal bladder functions well as an internal continent reservoir and that radionuclide investigation is a valuable and cost-beneficial means of follow-up of urinary diversions.

Aged↗

Temporary interruption of the left renal vein as an adjunct to resection of interaortocaval pheochromocytoma.

Although the left kidney has a number of venous collaterals, the collateral venous drainage is not always sufficient to allow permanent ligation of the venous trunk. Interruption and reanastomosis of the left renal vein were performed as an adjunct to dissection of extra-adrenal pheochromocytoma arising in the interaortocaval space. Reconstruction of the interrupted vein is a simple and reasonably acceptable technique to preserve the ipsilateral renal function. This maneuver, though practiced infrequently, facilitates the juxtarenal surgeries exposure of which is seriously hampered by the anatomical disposition of the left renal vein.

Adult↗

Frequent overexpression of vascular endothelial growth factor gene in human renal cell carcinoma.

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and an inducer of angiogenesis. Expression of the VEGF gene was investigated in 20 patients with renal cell carcinoma by Northern blot hybridization analysis. Of the 20 tumors, 12 (60%) overexpressed the gene 3.0 times more than in normal renal tissues. No significant correlation was found between overexpression of the VEGF gene and the histopathological data such as grade, cellular and structural subtypes, stage and size of tumor. These results suggest that VEGF is produced by the tumor cells and is responsible for development of this hypervascular tumor.

Adult↗

Alcaptonuria: a case complicated with valvular heart disease and immunodeficiency.

A 75-year-old man was diagnosed with alcaptonuria by direct identification of homogentisic acid in the urine using gas chromatography-mass spectrometry. Complications included valvular heart disease with marked calcification detected by two-dimensional color-Doppler echocardiography and recurrent bacterial infection. Immunological analyses revealed a reduced number of T cells with compensatory expansion of CD56+, CD57+ natural killer (NK) cell population and impaired functions of cellular immunity such as phytohemagglutinin response, antibody-dependent cellular cytotoxicity, NK activity and interleukin-2 production. Humoral immunity and neutrophil functions were considered to be normal. This is the first reported case of alcaptonuria to our knowledge in which immunological abnormality was documented.

Aged↗

[Chemoembolization with mitomycin C microcapsules (MMC-mc) in the treatment of bone metastases from prostatic and renal cancer].

The patients having bone metastases from prostatic and renal cancer, of whom 4 were resistant to prior radiotherapy, hormone therapy and/or chemotherapy, were subjected to arterial chemoembolization with mitomycin C microcapsules. In these patients, 12 metastatic lesions in the pelvic bone (5), lumbar spine (3), scapula (1) and rib (1) were treated. The mean size of the target lesions was 41.5 cm2 (range, 6-143). The mean number of microcapsule infusion into the tumor supplying arteries was 2.6 (1 to 10) and the mean interval of repeat infusion in 6 patients was 6.4 months (0.5 to 28). A complete remission of pain was obtained in 9 (75%) of the 12 evaluable lesions and a partial remission in 3 (25%). Motor disturbances were remarkably improved in all of the evaluable 6 lesions. Objective tumor response such as recalcification and reduction of size or vascularity was found in 9 (75%) of the evaluable 12 lesions. These effects were maintained for the mean follow-up period of 17.1 months (3 to 48). The results will indicate that this therapy can be used as an effective measure in the treatment of metastatic bone tumors.

Aged↗

[Targeting therapy for renal cancer].

Renal cancer is a typical tumor most insensitive to standard chemotherapy, but this hypervascular tumor has an anatomical feature by which its main feeding artery is readily accessible to transarterial targeting treatments. Effects of arterial chemoembolization, a prototype targeting chemotherapy, on renal cancer were reviewed.

Brachytherapy↗

[99mTechnetium-diethylenetriaminepentaacetic acid renoscintigraphy as a measure of renal function and urodynamics after uretero-ileoceco-proctostomy].

Ten patients having a uretero-ileocecoproctostomy (ileocecorectal bladder) were evaluated by 99mtechnetium diethylenetriaminepantaacetic acid renoscintigraphy, which was repeated at an approximately 1 year interval in 7 patients. The computed total glomerular filtration rates at the 1st and 2nd surveys were 100 +/- 23.2 and 92.7 +/- 23.0 ml/min (mean +/- S.D.), respectively indicating a minimal change with no statistically significant difference. The normal or incompletely obstructive renogram patterns were consistent with the pyelographic findings in 27 of 28 renal units, and 5 of 6 renal units with dilated nonobstructive renograms subsequently became normal both on the renograms and pyelograms. Comparing the data in the 1st and 2nd surveys, the frequency of colonic reflux decreases from 8/10 to 3/7 of the patients, the rectal bladder capacity increased from 82 +/- 18.8% to 92 +/- 20.8% of the excreted urine, and the total residual urine rate decreased from 40.4 +/- 12.9% to 28.0 +/- 16.6% (p = 0.1298), respectively. The results indicate that the ileocecorectal bladder, though it has no antireflux mechanism against colonic regurgitation, well functions as an internal continent urinary reservoir. Also, since this comprehensive information is obtained by a single procedure, the radionuclide evaluation can be practiced as a cost-beneficial measure for follow-up of patients with urinary diversions.

Aged↗

Determination of creatinine and ultraviolet-absorbing amino acids and organic acids in urine by reversed-phase high-performance liquid chromatography.

A simple and reliable method for the determination of urinary creatinine, amino acids and organic acids was developed. A urine sample was preliminarily separated into an organic acid fraction (including neutral species) and an amino acid fraction by cation-exchange chromatography. Both fractions were analysed by reversed-phase high-performance liquid chromatography, with a phosphoric acid-methanol gradient elution system and ultraviolet detection at 210 nm. Relationships between concentrations and peak heights were linear from 2 to 500 microM for the analytes. Overall recoveries were ca. 100%. The concentrations of creatinine for 37 urine samples, from 20 healthy newborns and from 17 patients with several inherited metabolic disorders, were 2.35 +/- 2.29 mM (ranging between 0.27 and 10.15 mM). The method was applied to the determination of several diagnostically useful metabolites in urine. The concentrations of phenylalanine and phenylacetic acid for five urine samples from patients with phenylketonuria were 347 +/- 177 and 282 +/- 224 microM/mM creatinine, respectively. The concentrations of tyrosine and 4-hydroxyphenyllactic acid in the urine of a patient with tyrosinemia were 112 and 1871 microM/mM creatinine, respectively.

Acidosis↗

Tumor-promoting effect of urinary epidermal growth factor in rat urinary bladder carcinogenesis.

We previously demonstrated that the specific component of rat urine designated as Fraction I (Fr.I), which has been known to enhance carcinogenesis in the rat urinary bladder, contains epidermal growth factor (EGF) and transferrin (TF). The present study was designed to determine whether EGF or TF is responsible for the tumor-enhancing effect of Fr.I. The heterotopically transplanted rat urinary bladder (HTB), which has been developed in our laboratory, was used for the study. Fr.I was prepared from normal rat urine by a method published previously. Fr.I deficient in EGF or TF was prepared by passing this fraction through an Affi-Gel Hz column coupled with anti-rat EGF or TF antibodies, respectively. EGF and TF eluted from the column (designated as eluted EGF and eluted TF) were also tested for tumor-enhancing activity. Fr.I passed through the column coupled with nonimmune rabbit IgG served as control (Fr.I column control). After initiation of carcinogenesis in HTBs by instillation of a single dose of 0.25 mg of N-methyl-N-nitrosourea, test materials were administered into these HTBs once a week for 30 weeks. The results showed that removal of EGF significantly reduced the tumor-enhancing effect of Fr.I (P less than 0.001 as compared to that of the Fr.I column control) and that eluted EGF by itself significantly enhanced the carcinogenesis as compared to that of the vehicle control (P less than 0.006). Removal of TF from Fr.I also reduced the tumor-enhancing effect of Fr.I (P less than 0.01). However, removal of both EGF and TF from Fr.I did not enhance the inhibitory effect demonstrated by the Fr.I which was deficient in EGF. Likewise, combined use of TF and EGF did not exceed the tumor-promoting effect of EGF. The results indicate that EGF in Fr.I may play a significant role in the promotion of bladder carcinogenesis by urine.

Animals↗

Simultaneous determination of urinary creatinine and aromatic amino acids by cation-exchange chromatography with ultraviolet detection.

A cation-exchange chromatographic procedure for the simultaneous determination of urinary creatinine and aromatic amino acids is described. Creatinine and amino acids were separated from organic acids and/or neutral species in urine by using a preparative cation-exchange resin column. A column packed with a cation-exchange resin of low capacity was used for the analytical separations. The elution of creatinine and aromatic amino acids was monitored at 210 nm by means of an ultraviolet detector. The relationships between concentration and peak heights were reproducible with a coefficient of variation of less than 2%, and were linear from 5 to 200 microM for each compound. Overall recoveries of the analytes were more than 95%. The method was applied to the analysis of urine of patients with disorders of amino acid metabolism, such as phenylketonuria. The concentration ratios of phenylalanine to creatinine in the patients' urine were accurately and easily determined, and were quite different from those in the urine of healthy newborns.

Amino Acid Metabolism, Inborn Errors↗