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Biomedical subjects

H Maezawa

Publications and source records attributed to H Maezawa.

At least 37 records · Page 2Linked to original sources

Sepsis associated with hematological malignancies: prophylaxis of Pseudomonas aeruginosa sepsis.

Underlying diseases, pathogenic bacteria, clinical background and outcome were studied during 91 febrile episodes complicated by sepsis in 55 patients with hematological malignancies, who had been admitted to our hospital (Jikei University Kashiwa Hospital) between January 1990 and December 1994. Particularly in patients with P. aeruginosa sepsis, we compared the prophylactic effect of ciprofloxacin (CPFX) alone with that of the combination of polymyxin B (PL-B) plus kanamycin (KM). The major underlying diseases were acute myelocytic leukemia and malignant lymphoma, followed by myelodysplastic syndrome, acute lymphocytic leukemia and chronic myelocytic leukemia. Nearly two-thirds of the pathogenic microorganisms isolated were gram-positive bacteria (including coagulase-negative staphylococci and Staphylococcus aureus); approximately one-quarter were gram-negative bacteria (such as Pseudomonas aeruginosa), and the remainder were fungi. These microorganisms usually induced sepsis when granulocyte counts were decreased. Sepsis was a direct cause of death in about 60% of the patients and P. aeruginosa sepsis had the worst outcome. Oral administration of CPFX was more effective than PL-B plus KM in preventing P. aeruginosa sepsis. The difference in effectiveness might depend on the absorption profile of the drugs.

Adolescent↗

[Two cases of gram-positive sepsis successfully treated with vancomycin in combination with imipenem or cilastatin].

Against gram-positive sepsis, vancomycin (VCM) was administered in combination with imipenem or cilastatin (IPM/CS). Its excellent efficacy was confirmed in 2 cases, one affected with methicillin resistant Staphylococcus aureus and another with Gemella morbillorum. By calculating the FIC index according to a checkerboard technique, the in vitro synergistic effect was also demonstrated. At the present state multi-drug resistant gram-positive infections prevailed, the combination of VCM with IPM/CS can be expected as an effective measure for treating these diseases.

Adolescent↗

Radiolytic products of bromodeoxyuridine in solids by 60Co gamma-rays and monoenergetic soft x-rays at the K-absorption edge of bromine.

In order to investigate DNA damage due to Auger cascades in bromodeoxyuridine (BrdU), BrdU mixed with other nucleosides, as a model of DNA, was irradiated in solids by gamma-rays and monoenergetic x-rays at around the K-absorption edge of bromine (13.47 keV). The main products of BrdU were deoxyuridine produced through debromination, and bromouracil produced through the decomposition of a sugar group. The rates of the debromination and the nucleobases release of additives were markedly increased in the mixed sample. This observation indicated that the additives surrounding BrdU efficiently supplied protons and then decomposed. The major products by x-rays were the same as those by gamma-rays, indicating that Auger cascades in bromine atoms did not produce specific products. The production rates for all products from the mixed sample were about 2.5 times higher at 13.51 (above the K-absorption edge) keV than at 13.43-keV x-rays.

Bromodeoxyuridine↗

Lethal effect of K-shell absorption of intracellular phosphorus on wild-type and radiation sensitive mutants of Escherichia coli.

The present study was conducted to clarify the lethality of Auger cascades induced by the K-shell photoabsorption of phosphorus in Escherichia coli. Killing of wild-type and radiation-sensitive mutants of E. coli was examined. Three x-ray energies were chosen for irradiation; at 2.153 keV: the resonance peak of K-shell photoabsorption of phosphorus; at 2.146 and 2.160 keV: off-peak. Enhancement ratio, which was defined as the ratio of the killing sensitivity of 2.153 keV to that at 2.146 keV, were 1.32 to 1.54 for examined strains. Increment of absorbed energy calculated in entire cells for 2.153 keV radiation could not explain the degree of observed enhancement of killing. Lethality of Auger cascades depended on the killing sensitivity with x-rays which did not induce Auger cascades. The lethality for wild-type was lower than that for recombination repair-deficient mutants. It was concluded that one part of damages produced by Auger cascades was repaired in wild-type strains.

Absorption↗

[Spinal multiple sclerosis mimicking a spinal cord tumor: a case report].

Since the advent of magnetic resonance imaging (MRI), to visualize lesions of multiple sclerosis has become easy to do. However, in some cases with primary spinal cord multiple sclerosis, it is not always easy to obtain a diagnosis in the first instance. We reported a case of primary spinal multiple sclerosis diagnosed through histological examination of a surgical specimen taken by an open biopsy. A 35-year-old woman was admitted with complaints of two-months duration of progressive weakness and sensory disturbance in the legs and buttocks. On radiological examinations including metrizamide CT myelography and MRI, enlargement of the conus medullaris was the only positive finding. Respective to her clinical course, intramedullary spinal cord tumor could not be ruled out, so an open biopsy was performed. Histological examination revealed that the cord lesion was acute demyelination with perivascular inflammation. Her neurological signs were almost completely cured with administration of corticosteroid, though new brainstem signs took place two months later and then a concrete diagnosis of her having multiple sclerosis was finally achieved. Since preoperative examinations can not differentiate spinal cord tumor from any other intramedullary cord lesions such as demyelinating foci of multiple sclerosis, surgical intervention would be approved in such atypical primary spinal cord multiple sclerosis.

Adult↗

Origin of ciliated craniopharyngioma: pathological relationship between Rathke cleft cyst and ciliated craniopharyngioma.

Histological study was undertaken on ciliated craniopharyngioma and Rathke cleft cyst, to know the origin of ciliated craniopharyngioma. Subjects were 7 cases with symptomatic Rathke cleft cysts and a ciliated craniopharyngioma. Light and electron microscopic observations were made on surgically resected specimens of the 8 cases. The ciliated craniopharyngioma was composed mainly of papillary type of craniopharyngioma and of dispersed ciliated columnar epithelium including goblet cells. Four cases with Rathke cleft cyst showed squamous metaplasia of which the basal cells were histologically similar to that of papillary type of craniopharyngioma. Other 3 cases of Rathke cleft cyst, basal cells were revealed to have tonofilaments and desmosomes. It seems possible that ciliated craniopharyngioma has derived from the basal cells of Rathke cleft epithelium.

Adult↗

Properties of single potassium channels in guinea pig hepatocytes.

The patch-clamp technique of cell-attached and inside-out configurations was used to study the single potassium channels in isolated guinea pig hepatocytes. The single potassium channels in isolated guinea pig hepatocytes were recorded at different K+ concentrations. A linear single-channel current-voltage relationship was obtained at the voltage range of -80 to -20 mV with slope conductance of 70 +/- 6 pS (n = 10). Under symmetrical high K+ concentration of 148 mM in the cell-attached patch membrane, the I-V curve exhibited a mild inward rectification at potentials positive to + 20 mV. The values of reversal potential was +5 +/- 2 mV (n = 10). When the external potassium concentration ([K+]o) was decreased to 74 mM and 20 mM, the slope conductance was decreased to 48 +/- 2 pS (n = 4) and 24 +/- 3 pS (n = 3), respectively. The reversal potential was changed by 58 mV for a tenfold change in [K+]o, indicating that this channel was highly selective for K+. Open probabilities (Po) of the channel were 73-93% without apparent voltage dependence. The distributions of open time of the channels were fitted to two exponentials, while those of closed time were fitted to three exponentials, exhibiting no voltage dependence. The success rate of K+ channel activity to be recorded was 28% at room temperature, and there were no increases in the success rate nor in the channel opening probabilities at a temperature of 34-36 degrees C. Po in inside-out patches was not changed by application of 1 microM Ca2+ nor 1 mM Mg2+ to the internal side of patch membranes. It is concluded that a novel type of the K+ channels in guinea pig hepatocytes had different properties of slope conductance, channel kinetics, and sensitivity to [Ca2+]i, from those in other species.

Animals↗

Uracil-DNA glycosylase produces excess lethal damage induced by an Auger cascade in BrdU-labelled bacteriophage T1.

T1 phages with and without 5-bromo-2'-deoxyuridine (BrdU) labelling were irradiated in solids with monochromatic X-rays at 12.40 and 13.51 keV, below and just above the K-absorption edge of bromine (13.47 keV) in vacuum and wet states. Irradiated phages were assayed on uracil-DNA glycosylase (Udg) deficient (ung-1) and sufficient (ung+) host strains of Escherichia coli, in order to investigate the nature of the lethal damage induced by Auger cascade following X-ray absorption at the K-shell of bromine as a key atom. The results were: (1) An Auger-specific enhancement (1.15) was observed only when BrdU-labelled phages were irradiated in the wet state and assayed on ung+ host cells. (2) A Udg-specific enhancement was observed only for BrdU-labelled phages, not for unlabelled phages. (3) The sensitivities of BrdU-unlabelled phages were almost the same, despite the irradiation states and strains of the host cell, indicating that this sensitivity was a common fraction of the sensitivity under all conditions. (4) The lethal damage for the T1 phage was categorized into four fractions according to the sensitivities under different conditions: the general fraction was defined as being the sensitivity of unlabelled phages (G-fraction); BrdU-specific, but unrecognizable by Udg (B-fraction); Udg specific, but not Auger-specific (U-fraction); and Auger-specific (A-fraction). (5) Although the so-called indirect action of water radicals increased only the G-fraction by about three-fold, the B- and U-fractions were not affected by any change in the irradiation states, thus indicating that these two fractions were caused by the so-called direct action.

Affinity Labels↗

[Treatment of severe pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA) and Candida krusei with granulocyte colony-stimulating factor (G-CSF): a case report].

A 24-year-old male with chronic renal failure on Continuous Ambulatory Peritoneal Dialysis (CAPD) complained of cough and dyspnea. Chest X-ray film showed a pneumonia shadow and MRSA and Candida krusei were detected in the sputum. Pneumonia improved with vancomycin and fluconazole. Treatment with methylprednisolone was needed for retinodialysis. After this treatment, pneumonia deteriorated. Pneumonia did not improve with vancomycin and anti-fungal agents. This severe pneumonia was improved with a combination therapy of vancomycin, miconazole and G-CSF. A combination therapy of antibiotics and G-CSF is considered to be effective for severe pneumonia.

Adult↗

[The local relapse of prostatic cancer and initial local treatment].

We treated fifty cases of prostatic cancer that had no distant metastasis and no other primary cancers between October 1983 and September 1990. Our initial treatment for clinical stages A2, B1, B2 included radical prostatectomy, pelvic lymphadenectomy, and bilateral orchiectomy. Staging lymphadenectomy with bilateral orchiectomy was applied to patients with clinical stage C tumor, and if there was no lymph node metastasis, external beam radiation therapy for the prostate was performed. Patients who did not consent to major surgeries or had poor general status or had clinical stage D1 tumor underwent bilateral orchiectomy. Mean observation period was forty-one months. Eleven cases relapsed. Of the eleven cases, ten had local relapse at the diagnosis of relapse (two of them had distant metastasis simultaneously, six of them had distant metastasis later, and two of them had no distant metastasis in the observation period). All these ten cases had no underwent the initial local treatment. The remainder who had underwent radical prostatectomy relapsed with distant metastasis alone. This study suggests that the local relapse tends to precede distant metastasis as the mate of relapse of prostatic cancer excluding stage D2. There is a possibility that initial local treatment is useful improving the prognosis of the patients for clinical stage A2-D1 prostatic cancer.

Adenocarcinoma↗

Synergistic effects of hyperthermia and intratumorous injection of anti-cancer drugs.

In an attempt to improve the combined effects of hyperthermia and anti-cancer drugs, an intratumorous (i.t.) injection of the drugs was performed and its effect compared with that obtained by intraperitoneal (i.p.) injection. Using Lewis lung carcinoma growing in the legs of BDF1 mice, weakly toxic drug derivatives, Aclarubicin (ACR), a new platinum complex (DWA2114R), or Peplomycin (PEP) were injected either into the center of the tumors, or intraperitoneally, before or after usual hyperthemia in a 43.5-43.7 degrees C water bath for 45 min. The effects on tumor growth delay and the number of lung metastases were assessed, and the enhancement ratios (ERs) due to the combination were calculated. Tumor growth inhibition by i.t. injection was enhanced additively with ACR (ER; 1.2) and synergistically with DWA2114R (ER; 3.49) and PEP (ER; 2.4) plus hyperthermia. Hyperthermia after i.t. injections of DWA2114R (ER; 3.4) was more effective than either i.t. or i.p. injections after hyperthermia (ER; 2.4). Lung metastases were also inhibited significantly by the combination of hyperthermia and drugs, except when emulsified PEP was injected three times. It was concluded that the i.t. injection of DWA2114R was of value when used in combination with hyperthermia.

Aclarubicin↗

Radiosensitivity of mouse skin epithelial cell line established in serum-free culture: an alternative to animal use.

A cultured line of murine skin epithelial cells was established to investigate the potential use of cultured cells as an alternative to animal use in radiation research. C3Hf/Sed newborn mouse skin cells have been successfully cultured in serum- and Ca(2+)-free medium with no terminal differentiation to keratinized cells. Presently, more than 25 passages have passed with no loss of stem cell capability. The radiosensitivity and repair of sublethal and potentially lethal radiation damages were investigated in this epithelial cell line. The population cell doubling time was 25 +/- 2.9 hr at 37 degrees C. The clonal growth of epithelial cells after irradiation was performed in the serum-free medium in the presence of lethally irradiated skin fibroblasts. Single dose survival curves of exponentially growing epithelial cells were investigated from the seventh to the twenty-third passages, and no significant changes in radiosensitivity and doubling time were found. The confluent epithelial cells also showed an identical sensitivity to radiation. The alpha/beta ratios of survival curves fitted by the linear quadratic model were 6.1 +/- 1.0 and 5.9 +/- 1.3 Gy for cells in exponential and confluent phases, respectively. The survival curve of epithelial cells left in confluence for 8 hr after irradiation showed a smaller beta value than that of cells plated immediately after irradiation with a resultant alpha/beta ratio of 9.5 +/- 3.8 Gy. This alpha/beta ratio was identical to those found in many animal experiments, suggesting a potential use of this cell line as an alternative to animal use. The magnitude of repair of sublethal damage following 6 Gy was greater than that following 3.9 Gy. Survival curves were also obtained following twice-a-day irradiations with no sign of rapid repopulation. These results are discussed by comparing with published in vivo and in vitro data.

Animal Testing Alternatives↗

Iron(II) sulphate (Fricke solution) oxidation yields for 8.9 and 13.6 keV X-rays from synchrotron radiation.

The oxidation yields (G) for 8.86 and 13.55 keV X-rays produced by synchrotron radiation were measured using an iron(II) sulphate (Fricke) solution. Monoenergetic X-rays were produced using a silicon crystal monochromator. The X-rays were absorbed in 0.4 M sulphuric acid-iron(II) sulphate solution and FeIII ion yields were measured and corrected for escape fractions resulting from scattering using Monte Carlo calculations. Doses in the solution were determined using a thin window, parallel plate chamber calibrated against a primary standard free-air chamber at the Electrotechnical Laboratory (Osaka, Japan). Yields (G) of 1.50 +/- 0.06 and 1.43 +/- 0.06 mumol J-1 were obtained for 8.86 and 13.55 keV X-rays respectively.

Oxidation-Reduction↗

Ca(2+)-activated K+ channel is present in guinea-pig but lacking in rat hepatocytes.

The mechanisms of norepinephrine-induced membrane responses in isolated hepatocytes from guinea-pigs and rats were compared using the suction-pipette, patch-clamp method, and intracellular Ca2+ concentration ([Ca2+]i) was measured using the Ca2+ fluorescent dye, Quin 2. The resting membrane potentials of isolated guinea-pig hepatocytes were -50 +/- 1 mV (mean +/- SD; n = 38), which is similar to that previously reported in rat hepatocytes by Sawanobori et al. (J Cell Physiol 139: 580-585, 1989). In guinea-pig hepatocytes, norepinephrine (6 microM) caused a membrane hyperpolarization, and norepinephrine (6 microM) or Ca(2+)-ionophore (A23187) (0.4 microM) caused a corresponding outward current. The sensitive current produced by norepinephrine and Ca(2+)-ionophore reversed its polarity at -74 +/- 9 mV (n = 7). The single channel recorded by cell-attached patch and inside-out patch had mean conductance of around 20 + 1 pS and was activated by 1 microM [Ca2+]i. On the other hand, neither norepinephrine (6-20 microM) nor Ca(2+)-ionophore (A 23187) (0.4 microM) caused any change in membrane potential and current in rat hepatocytes, whereas norepinephrine increased [Ca2+]i both in rat and guinea-pig hepatocytes to a similar degree. In the single-channel recording, we recorded single channels that had a mean conductance of 109.8 +/- 17.7 pS different from around 20 pS in guinea-pig. In inside-out patches, increased Ca2+ concentration from 10(-6) to 10(-3) M at the intracellular face of the membrane did not modify the single channel of rat hepatocytes. These results indicate that increased [Ca2+]i activates this channel in guinea-pigs, but that the channel activated by increased [Ca2+]i is lacking in rat hepatocytes membrane. Therefore, different mechanism operates in different species of liver cells to keep the constant state.

Animals↗