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Biomedical subjects

M Nakano

Publications and source records attributed to M Nakano.

At least 433 records · Page 24Linked to original sources

Determination of IgA- and IgM-rheumatoid factors in patients with rheumatoid arthritis with and without nephropathy.

OBJECTIVE: To clarify the characteristics and pathogenesis of renal disorders in patients with rheumatoid arthritis (RA). METHODS: In this study, 143 patients with RA were included, from whom 43 with urinary abnormalities were biopsied. Serum rheumatoid factor (RF) concentrations of IgA and IgM isotypes were also measured in these patients by enzyme linked immunosorbent assay. RESULTS: Light microscopy of renal biopsy specimens showed minor glomerular abnormalities in six patients, mesangial proliferative glomerulonephritis (GN) in 21, membranous nephropathy in seven, renal amyloidosis in seven, and tubulointerstitial nephritis in two. Twelve patients with mesangial proliferative GN and one with minor glomerular abnormalities were found by immunofluorescence microscopy to have abnormalities consistent with IgA GN. Although the concentrations of IgA-RF in patients with IgA GN were slightly raised compared with those with glomerulopathy established by biopsy but not associated with IgA GN, the concentrations of IgA-RF were higher in patients with RA with vasculitis or interstitial pneumonia than those with RA complicated by IgA GN. CONCLUSIONS: Mesangial proliferative GN, including IgA GN, may be a frequent renal lesion in Japanese patients with RA. IgA-RF may play little pathogenetic part in the development of IgA GN in RA.

Adult↗

Tumor necrosis factor-alpha-induced expression of heat shock protein 72 in adult feline cardiac myocytes.

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that is elaborated in a myriad of cardiac disease states. Although the biological role for TNF-alpha in the adult heart is not known, a recent study in fetal myocardial cells has shown that this cytokine increases the synthesis of low-molecular-weight stress proteins. These findings suggested the interesting possibility that TNF-alpha might play a functional role in the adult heart by increasing the expression of stress proteins in cardiac myocytes. Accordingly, the purpose of this study was to determine whether TNF-alpha would modulate the expression of heat shock protein 72 (HSP 72), a stress protein that is thought to exert protective effects in the adult heart. Stimulation of adult feline cardiac myocytes with a range of TNF-alpha concentrations (10-1,000 U/ml) for 12 h showed that concentrations of TNF-alpha < or = 10 U/ml had no effect on HSP 72 expression: increased HSP 72 expression was detected 3 h following cytokine stimulation, peaked by approximately 12 h, and then returned toward baseline by 48 h. Additional studies indicated that stimulation of the type 1 TNF receptor was responsible for the increase in HSP 72 expression. In summary, these studies constitute the initial demonstration that TNF-alpha exerts concentration- and time-dependent effects on the expression of HSP 72 in the adult mammalian cardiac myocytes, thus suggesting the interesting possibility that the elaboration of TNF-alpha may enable the heart to better withstand certain forms of stress.

Animals↗

Acyclothymidine alleviates intestinal toxicity of 5'-deoxy-5-fluorouridine without loss of antitumor activity in mice.

To reduce the intestinal toxicity of orally administered 5'-deoxy-5-fluorouridine (5'-DFUR) in mice, we co-administered 5'-DFUR with acyclothymidine [AcyT, 5-methyl-(2'-hydroxyethoxymethyl) uracil], a potent inhibitor of pyrimidine nucleoside phosphorylase (PyNPase). Orally administered 5'-DFUR alone caused intestinal toxicity and severe damage to the intestinal villi, while 5'-DFUR with AcyT reduced the intestinal toxicity, and prevented damage to the intestinal villi. This toxicity arising from orally administered 5'-DFUR could not be reduced by intravenous administration of AcyT, but was alleviated by oral administration. Orally co-administered AcyT showed little effect on antitumor activity of 5'-DFUR toward subcutaneously implanted Lewis lung carcinoma, though the intestinal toxicity was reduced in the tumor-bearing mice. This finding suggests that orally co-administered AcyT may prevent the undesirable conversion of 5'-DFUR to 5-FU by PyNPase during the process of absorption in the intestinal tract.

Administration, Oral↗

Protective effects of N-benzoyl amino acids on cisplatin nephrotoxicity in rats.

The protective effects of N-benzoyl amino acids (NAAs) and piperacillin (PIP), anionic transport inhibitors, against the nephrotoxicity of cisplatin were examined in rats. Male Wistar rats were injected i.p. with 6 mg/kg of cisplatin combined with i.p. NAAs or PIP. Rats were sacrificed on day 5 after cisplatin injection to weigh the kidney and liver, and to determine blood urea nitrogen (BUN) and serum creatinine (serum Cr) levels. Treatments with NAAs were an effective means of protection against cisplatin-induced nephrotoxicity. The combination of cisplatin with NAAs containing a short and straight chain significantly suppressed (p < 0.05) the changes in body, kidney and liver weights, BUN and serum Cr. Further, betamipron (BP) at a 2000 mg/kg dose showed no apparent effect on the body, kidney and liver weights, BUN and serum Cr levels in rats. The combination of cisplatin with PIP caused a loss in body weight. The protective effects of PIP against cisplatin toxicity are inferior to those of BP when compared at 250 mg/kg doses.

Alanine↗

Examination of stability of anticonvulsants in a protease solution and assay of anticonvulsants in hairs.

For analyzing the concentrations of drugs in hairs, a new method of digestion of hairs with Biopurase, a protease obtained from Bacillus subtilis, was examined. The concentrations of drugs in hairs were then determined in order to examine the usefulness of the protease for the digestion of hairs. The stability of five anticonvulsants in the protease solution was maintained over a 12-h period. In the clinical tests, the concentrations of the drugs in hairs obtained from patients who were taking anticonvulsants for a long time were determined. The concentration of phenobarbital in hairs in 10 patients taking phenobarbital ranged from 194 to 5020 ng/10 mg with a mean of 578 ng/10 mg, and the concentration of phenytoin in hairs in 6 patients taking phenytoin ranged from 44 to 299 ng/10 mg with a mean of 115 ng/10 mg. From these results, the transfer of phenobarbital and phenytoin from circulating blood into hairs was confirmed, and the usefulness of Biopurase for the digestion of hairs was proved.

Anticonvulsants↗

Modulation of the pharmacokinetics of 5'-deoxy-5-fluorouridine and 5-fluorouracil in rats by oral co-administration of acyclothymidine.

The effect of an inhibitor of pyrimidine nucleoside phosphorylase (PyNPase), acyclothymidine (AcyT), on the pharmacokinetics of 5'-deoxy-5-fluorouridine (5'-DFUR) and 5-fluorouracil (5-FU) was investigated in an oral co-administration of 5'-DFUR and AcyT in rats. AcyT increased the maximal plasma concentration (Cmax) and apparent absorption rate constant (ka) of 5'-DFUR, as expected, but the increase in AUC (area under the curve) was not significant. It was expected that AcyT would only inhibit the phosphorolytic degradation of 5'-DFUR to 5-FU, but the effect was more evident on the pharmacokinetic parameters of 5-FU than on those of 5'-DFUR. AcyT also increased AUC and Cmax of 5-FU when orally co-administered with 5-FU. An inhibitory effect of AcyT on the enzymatic degradation of 5-FU in rat liver and intestinal extract was investigated. AcyT inhibited the degradation in intestinal extract but not in the liver. The result suggests that orally administered AcyT affects the pharmacokinetics of 5-FU partly by inhibiting 5-FU degradation in the process of intestinal absorption as well as by acting as an inhibitor of PyNPase.

Administration, Oral↗

Assay for antiviral activity of herbal extracts using their absorbed sera.

We evaluated an antiviral assay procedure using serum obtained from guinea pigs administered 32 herbal extracts. In this assay, 21 of the 32 showed anti-herpes simplex virus type 1 (HSV-1) activity in serum. Ten of the 21 exhibited therapeutic anti-HSV-1 activity, and this was consistent with our previous results that 12 of the 32 were effective in murine infection models. Therefore, the serum pharmacological assay procedure was suitable for the selection of possible herbal extracts with biological activity in vivo as a pre-screening method before animal experiments.

Animals↗

Purification and properties of a novel enzyme, trehalose synthase, from Pimelobacter sp. R48.

A novel enzyme, trehalose synthase, was purified from a cell-free extract of Pimelobacter sp. R48 to an electrophoretically homogeneous state by successive chromatographies on DEAE-Toyopearl 650, Butyl-Toyopearl 650, and Mono Q HR5/5 columns. The molecular weight of the enzyme was estimated to be 62,000 by SDS-polyacrylamide gel electrophoresis, and the enzyme had a pI of 4.6 by gel isoelectrofocusing. The enzyme catalyzed the conversion of maltose into trehalose by intramolecular transglucosylation. The enzyme also converted into maltose but was inactive on other saccharides. The N-terminal amino acid of the enzyme was serine. The optimum pH and temperature were pH7.5 and 20 degrees C, respectively. The enzyme was stable in the range of pH 6.0-9.0 and up to 30 degrees C for 60 min. The rate of conversion of maltose into trehalose was independent of the maltose concentration. The maximum yield of trehalose from maltose were 81.8%, 80.9%, and 76.7% at 5, 15, and 25 degrees C, respectively. The activity was inhibited by Cu2+, Hg2+, Ni2+, Zn2+, and Tris.

Amino Acid Sequence↗

Resident gynecologists and total hysterectomy.

We examined the specific number of surgeries necessary for a three-year obstetrics and gynecology resident to acquire proficiency in two types of hysterectomies. Improvement in the technical skills of the residents was assessed using surgical time and blood loss, and resected tumor weight was chosen as the factor representing the difficulty of the surgery. Regarding abdominal total hysterectomy (ATH), early residents (less than 25 ATH experience) performed relatively easier surgeries, and improvement in technical skill was manifested as reduced blood loss by mid residents (25 to 49 ATH) and as shortened surgical time by later residents (75 or more ATH). Regarding vaginal total hysterectomy (VTH), blood loss for earlier residents (less than 15 VTH) was greater than that for the staff, and there was a significant difference between staff surgical time and that for each resident group. These data suggest that performing more than 75 ATH during the residency period of three years is adequate to establish proficiency in this type of surgery, but that the execution of 25 VTH is insufficient and that residents require more training to learn VTH.

Blood Loss, Surgical↗

Evaluation of cardiac function by echocardiography in dogs treated with doxorubicin.

Cardiac functions were evaluated by echocardiography in dogs treated with doxorubicin. The dogs were administered 1.5 mg/kg body-weight doxorubicin intravenously at intervals of 3 weeks. Two-dimensional echocardiography of several sections of the heart was taken and fractional shortenings of chordal and papillary muscle levels were measured from M-mode echocardiogram to assess the left ventricular contractile function. And color Doppler and pulse Doppler examinations of mitral flow velocity were performed. Concomitantly, electrocardiogram (ECG) was also examined. The animals with decreased cardiac function were euthanized and the hearts were examined histologically. Fractional shortening was reduced gradually in the dogs treated with doxorubicin. And mitral regurgitation during systolic phase and changes of mitral flow velocity during diastolic phase were also revealed in the dogs with severe reduction of fractional shortening. These changes might indicate the reduction of cardiac functions, both of contractility and diastolic filling functions. ECG abnormalities, which were small changes, revealed only in the dogs that had severe reduction of fractional shortening and mitral regurgitation. In histological examination, myocardial degeneration was observed. And, the degree of myocardial damage might be relative to alteration of fractional shortening. Thus, the result demonstrates that the early alteration of cardiac function induced with doxorubicin can be detected by echocardiography in dogs. The result also indicates that cardiac function predicted by fractional shortening measured from M-mode echocardiogram might be correlated with histological changes of myocardium.

Animals↗

Protective effect of N-benzoyl-beta-alanine against cisplatin nephrotoxicity in rats.

Prophylactic effects of N-benzoyl-beta-alanine (betamipron, BP), one of a series of N-acyl amino acids, were examined against cisplatin-induced nephrotoxicity. Male Wistar rats were injected i.p. with 6 mg/kg of cisplatin combined with an i.p. BP dose given at various times and various doses. Rats were sacrificed 5 days after cisplatin injection to weigh the kidney and liver, and to determine blood urea nitrogen (BUN) and serum creatinine (serum Cr) levels. Preliminary results suggest that treatment with BP is an effective means of protection against cisplatin-induced nephrotoxicity. Combination with BP reduced the weight loss following treatment with cisplatin. The ratios of the kidney and liver weights to the body weight in the animals treated with cisplatin followed later with BP are significantly different (p < 0.05) from those in the animals that received only cisplatin. The BUN and serum Cr levels in the animals treated with cisplatin followed from -1 to 4 hr, and from -4 to 4 hr later with 250 mg/kg BP dose and followed 1 hr later with from 250 to 1000 mg/kg, and from 250 to 2000 mg/kg BP doses differed significantly (p < 0.05) from those in the animals that received only cisplatin. Histological analysis of the kidneys confirmed the protective effect of BP.

Alanine↗

Prognostic factors for local control in hypopharyngeal cancer treated with radical irradiation.

PURPOSE: We retrospectively analyzed prognostic factors for local control in hypopharyngeal cancer. PATIENTS AND METHODS: Twenty-five patients with hypopharyngeal cancer treated with radical irradiation were entered into analyses. Local control according to clinical T stage and subsites of hypopharynx were analyzed. For 8 clinical T2 patients, local control according to findings assessed by pretreatment CT was also evaluated. RESULTS: The 2-year local control rates were 40% for all, 1/2 for T1, 8/11 (73%) for T2, 1/8 (12%) for T3, and 0/4 for T4. Two-year local control rates were 28% for pyriform sinus cancer and 66% for pharyngeal wall cancer. Local control analysis according to CT findings for patients with T2 hypopharyngeal cancer showed that patients without specified involvement beyond the hypopharynx or in the apex had good local control. CONCLUSION: Our preliminary analysis suggested that clinical T2 hypopharyngeal cancer patients without invasion beyond the hypopharynx or in the apex demonstrated on CT had favorable local prognosis when treated with radical irradiation.

Aged↗

[Leiomyosarcoma of the scrotum: a case report].

A case of leiomyosarcoma of the scrotum is reported. A 44-year-old man referred to our hospital with the complaint of swelling of the left scrotal contents. The lesion was about 3 cm in diameter, isolated from testis, epididymis and spermatic cord. Ultrasonography revealed hypoechoic and slightly heterogenic area in the lesion. Surgical resection was easily done. Histological examination showed leiomyosarcoma. Adjuvant therapy was not performed. Three years after the resection, he is alive without any sign of recurrence or metastasis.

Adult↗

Isolation of a cosmid clone corresponding to an inv(21) breakpoint of a patient with transient abnormal myelopoiesis.

Transient abnormal myelopoiesis (TAM) is a leukemoid reaction occurring occasionally on Down syndrome (DS) newborn infants. It has been hypothesized that "disomic homozygosity" in 21-trisomic cells plays an important role in the genesis of TAM, and the putative TAM gene was suggested to be mapped at a 21q11 region. We encountered a DS-associated TAM infant with a 47,XY,inv(21)(q11.1q22.13),+inv(21)(q11.1q22.13) karyotype. On the basis of another presumption that in this patient the putative TAM gene is disrupted by the break, we tried to isolate a breakpoint DNA. FISH analysis with cosmid clones corresponding to various sequence-tagged-site (STS) markers mapped at around 21q11.1-q11.2, we confirmed that the proximal breakpoint of the inv(21) was located between two STSs, G51E07 and D21S215, the latter locus being consistent with the previous tentative mapping. After construction of a cosmid contig encompassing between the two markers, we have isolated a cosmid clone corresponding to the proximal breakpoint of the inversion. This breakpoint was located near a previously identified duplicated region that is homologous to the sequence at 21q22.1. The isolated cosmid clone is useful for analysis of other TAM patients and for a search for a transcript at or flanking the breakpoint.

Adult↗

Regional vascular effects of MPC-1304, a novel dihydropyridine derivative, in conscious normotensive and spontaneously hypertensive rats.

The purpose of this study was to compare the regional vascular effect of a novel dihydropyridine derivative, MPC-1304 [(+/-)- methyl-2-oxopropyl-1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3, 5-pyridinedicarboxylate], with that of nifedipine and manidipine in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The radioactive microsphere technique was used to measure systemic and regional hemodynamic parameters before and 1 hr after p.o. administration of drugs. In SHR, MPC-1304 at a dose of 1 mg/kg reduced the mean blood pressure and systemic vascular resistance and increased cardiac output, as did nifedipine (10 mg/kg) and manidipine (3 mg/kg). MPC-1304, as well as nifedipine, significantly increased the blood flow in pulmonary, gastric, small intestinal and skeletal muscular beds and reduced their vascular resistance. Manidipine increased regional blood flow only in small intestinal and skeletal muscular beds. Only MPC-1304 increased the renal blood flow. In WKY, MPC-1304 and nifedipine reduced the mean blood pressure and systemic vascular resistance to lesser degrees than in SHR. Both drugs significantly increased coronary and skeletal muscular blood flow. MPC-1304 significantly reduced the renal blood flow without altering renal vascular resistance, in striking contrast to its renal effect in SHR. These findings suggest that MPC-1304 possesses a genetic hypertension-dependent renal vasodilating action, unlike nifedipine and manidipine. One possible mechanism for this difference in the effect on renal circulation between SHR and WKY may involve the potent antagonizing effects of MPC-1304 on alpha-2 adrenoceptor-mediated vasoconstriction.

Animals↗

[High activity of antistreptolysin-O in a case of IgM myeloma].

A 56-year-old man was admitted to our hospital in November, 1991 because of hyperproteinemia and anemia. Total protein showed 12 g/dl and serum immunoglobulins were as follows; IgG 974 mg/dl, IgA 142 mg/dl, IgM 9270 mg/dl. M-component was identified as IgM-kappa with immunoelectrophoresis and serum viscosity indicated 6.9. Although the patient had no history of severe streptococcal infection, his serum showed very high activity of ASLO (6890 IU/ml). Bence Jones protein was detected in the urine and determined to be of kappa-type. Plasma cells occupied 43% of bone marrow nucleated cells and their cytoplasms were stained with FITC-labeled anti-IgM and anti-kappa antibodies. X-ray examination disclosed punched out lesions in the skull. Consequently, the patient was diagnosed as having IgM-myeloma. At first, VCAP regimens were given after plasmapheresis, but had no effect. Therefore, the patient was treated with CHOP protocol and the serum IgM decreased in amount and the proportion of bone marrow myeloma cells got down to 17%. ASLO titer also decreased in parallel with IgM. These findings suggest that IgM in this case had ASLO activity.

Antistreptolysin↗

[Lymphocyte subsets in bronchoalveolar lavage fluid from patients with idiopathic interstitial pneumonia].

Lymphocyte activation may be involved in interstitial inflammatory processes in the lungs. We analyzed lymphocytes in bronchoalveolar lavage fluid obtained from 15 patients with idiopathic interstitial pneumonia (IIP) and from 7 controls. Clinical criterial were used to divide the patients with IIP into two groups: acute (n = 5) and chronic (n = 10). Lymphocytes in the bronchoalveolar lavage fluid were analyzed with a flow-cytometric two-color system. Differential cell counts showed that percentages and numbers of lymphocytes were significantly higher in patients with acute IIP (44.2 +/- 25.2%, 12.3 +/- 8.18 x 10(4)/ml) than in controls (8.31 +/- 3.66%, 0.69 +/- 0.39 x 10(4)/ml, p < 0.05) and in patients with chronic IIP (8.44 +/- 6.11%, 1.58 +/- 1.08 x 10(4)/ml, p < 0.05). In particular, percentages and numbers of CD8+ S6F1+ lymphocytes, which are regarded as activated cytotoxic T lymphocytes were markedly higher in patients with acute IIP (32.3 +/- 16.0%, 39.6 +/- 37.1 x 10(3)/ml), than in controls (6.31 +/- 1.69%, 0.42 +/- 0.25 x 10(3)/ml, p < 0.05) and in patients with chronic IIP (10.6 +/- 6.16%, 1.88 +/- 1.42 x 10(3)/ml, p < 0.05). These data suggest that patients with acute IIP differ from those with chronic IIP in the percentage and the number of lymphocytes in bronchoalveolar lavage fluid, and that activated cytotoxic T lymphocytes may play an important role in the pathogenesis of acute IIP.

Acute Disease↗