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Biomedical subjects

H Baba

Publications and source records attributed to H Baba.

At least 289 records · Page 16Linked to original sources

Spinal cord evoked potentials in cervical and thoracic myelopathy.

We have studied 70 patients who underwent surgical decompression with or without fusion for cervical and/or thoracic myelopathy to assess the value of spinal cord evoked potentials (SCEP). The 70 patients included 42 with cervical spondylotic myelopathy, 10 with ossification of the posterior longitudinal ligament of the cervical spine and 18 with thoracic ligamentous ossification. Abnormal SCEP occurred in 88% of the patients with cervical myelopathy. Early recovery in intra- and postoperative SCEP was associated with a better result. The severity of myelopathy correlated significantly with an abnormal SCEP in thoracic myelopathy. SCEP may reflect the severity of disease, and early recovery of intraoperative SCEP may also predict neurological improvement.

Adult↗

Intermittent claudication of the spinal cord due to ossification of the ligamentum flavum. A report of two cases.

Two patients are described who developed intermittent claudication of the spinal cord which caused spastic paraparesis during walking. The cause in both was multi-level ossification of the ligamentum flavum. Epidural spinal cord evoked potentials showed disappearance of the third negative component in one case, and positive-going waves in the most compressed area. Both patients had excellent neurological improvement after resection of the ossified ligament.

Adult↗

Distribution of polymorphic gene duplication at the Gpdh locus in natural populations of Drosophila melanogaster.

The glycerol-3-phosphate dehydrogenase (GPDH, E.C. 1.1.1.8) gene of Drosophila melanogaster contains a tandem duplication of a 4.5-kb-long DNA fragment. Survey of the Gpdh gene region by the Southern blot analysis revealed the following features of this gene duplication: (1) The duplication was not observed in chromosome lines that carry In(2L)t, a cosmopolitan chromosomal inversion in this species. The duplication and the inversion are in linkage disequilibrium. (2) The duplication is polymorphic in the Japan and US natural populations examined. Its frequency is 0.26 on an average in In(2L)t-free chromosomes. (3) Triplication is absent or has not become frequent in the populations surveyed. Possible evolutionary factors of this duplication polymorphism are discussed.

Alleles↗

Effect of hyperthermia on the activity of 1-[(4'-hydroxy-2'-butenoxy)methyl]-2-nitroimidazole, which is cytotoxic to hypoxic cells.

The effect on EMT6/KU cells of a newly synthesized hypoxic cell sensitizer, 1-[(4'-hydroxy-2'-butenoxy)methyl]-2-nitroimidazole (RK28), combined with heat was determined in vitro under conditions of hypoxia. As compared with aerobic conditions, hypoxia produced a 1.30-fold increase in the cytotoxicity of the drug for mouse mammary EMT6/KU cells induced by 1 h heat treatment at 43 degrees C in medium with a normal pH. Hypoxia also reduced the surviving fraction of cells treated with both RK28 alone for 2 h and the same concentrations of RK28 and heat (43 degrees C) in combination. Those enhancement ratios corresponded to a 20.3- and > 345-fold increase, respectively. Moreover, concomitant treatment with RK28 and heat greatly inhibited the clonogenic activity of the EMT6/KU cells under conditions of in vitro hypoxia and in all experimental groups; there was a statistically significant difference in the time-response curves (P < 0.05). As hypoxic cells in a solid tumor are resistant to various anticancer drugs, RK28 combined with hyperthermia deserves further study for possible clinical applications.

Animals↗

Postoperative PSK and OK-432 immunochemotherapy for patients with gastric cancer.

We evaluated the effects of chemotherapy given postoperatively with and without immunomodulators on the survival of patients who had undergone resection for gastric cancer. We conducted a retrospective survey of data on 963 Japanese patients treated at our department of surgery between 1965 and 1987. Data related to the duration of postoperative survival were calculated for those who received chemotherapy, i.e. an individualized combination of various agents given with or without the immunomodulators PSK, a protein extract of the fungus Coriolus versicolor, and/or OK-432, a preparation of an attenuated strain of Streptococcus (immunochemotherapy). Postoperative immunochemotherapy was more often prescribed for patients with advanced disease. The survival of patients who received immunochemotherapy was shorter than that of patients who received only chemotherapy. In a subgroup of patients adjusted for disease stage, the survival of those on chemotherapy versus immunochemotherapy did not differ significantly at any stage. For optimal results, a protocol for postoperative immunochemotherapy needs to be designed and investigated prospectively and according to the stage of gastric cancer. The stage III gastric cancers seem amenable to a favorable response.

Adjuvants, Immunologic↗

Expression of myelin-associated glycoprotein isoforms after sciatic nerve crush injury in mice.

The large myelin-associated glycoprotein isoform (L-MAG) protein and small myelin-associated glycoprotein isoform (S-MAG) protein were demonstrated after sciatic nerve crush injury in mice by an immunoblotting technique using specific antibodies to the L-MAG protein and the S-MAG protein, respectively. Immunoblots indicated a rapid decrease in expression of both isoform proteins in the crushed sciatic nerves to < 10% of the control side. By 13 d after injury, L-MAG protein expression had quickly recovered to 100% of the control level. Following the increase in L-MAG protein expression, S-MAG protein expression recovered to 100% by 20 d after injury. It has been reported that the developmental maximum expression of L-MAG protein precedes that of S-MAG protein in both central and peripheral nervous system (CNS and PNS). Our previous work demonstrated that L-MAG mRNA was characteristically induced at the time of most active myelination, including remyelination in the CNS. We here have shown the expression of L-MAG protein precedes that of S-MAG protein during active remyelination in the PNS. This suggests that it plays an important role in the early stage of myelin formation.

Animals↗

Gastric cancer with p53 overexpression has high potential for metastasising to lymph nodes.

Overexpression of the tumour suppressor gene p53 was investigated immunohistochemically in 96 primary gastric carcinomas and 26 corresponding metastatic perigastric lymph nodes. Abnormalities in p53 expression were found in 52 (54%) of the 96 primary carcinomas. Tumours stained positively for p53 frequently metastasised to lymph nodes (the metastatic rate: 85%) compared to findings in those with negative p53 staining (64%, P < 0.05). Ninety-two percent (24/26) of the malignant cells in the lymph nodes stained positively for p53. When the DNA ploidy pattern of the tumour was determined by flow cytometry, the aneuploid tumours in p53 positive and negative groups accounted for 69% and 45%, respectively (P < 0.05). Proliferative activity of the tumour, as measured by Ki-67 labelling, was significantly higher (30.6 +/- 12.0%) in the p53 positive group than that (25.1 +/- 10.7%) in the p53 negative group (P < 0.05). Thus, gastric cancer with a mutant p53 has high proliferative activity and metastasis to lymph nodes will probably occur.

DNA, Neoplasm↗

Sequence dependence of the hyperthermic potentiation of carboplatin-induced cytotoxicity and intracellular platinum accumulation in HeLa cells.

We have examined the enhancement of cytotoxic effects of cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) (carboplatin) by hyperthermia in HeLa cells using different regimes of timing and sequence. The results were compared with those obtained with cis-diamminedichloroplatinum(II) (cisplatin). We found that cisplatin simultaneously combined with heat was the most cytotoxic toward HeLa cells of the various timing and sequencing conditions studied. On the other hand, for carboplatin, drug treatment immediately following or during heat exposure showed the greatest effect. Intracellular platinum concentration in HeLa cells treated with heat before carboplatin showed a 2.75-fold increase over that in cells treated with the drug alone. The ratios for carboplatin given before, or during heating, were 0.67 and 1.42 respectively. Simultaneous exposure of cells to cisplatin and heat led to a 1.64-fold enhancement in cisplatin accumulation, compared to 0.92- and 1.24-fold increase for cells treated with cisplatin before and after heat respectively. Although each drug exposure prior to heat was less cytotoxic toward HeLa cells than any other heat/drug combination sequences, the platinum concentration was less than seen with each drug alone. Even though heat exposure prior to and during carboplatin showed a similar toxicity, platinum concentration in cells treated with heat prior to carboplatin was higher than that in cells treated with heat and carboplatin simultaneously. Thus, increased cytotoxicity cannot always be explained on the basis of intracellular platinum concentration. It is clear however that, differing from cisplatin, exposure of cells to heat prior to or during carboplatin administration results in the greatest cell kill.

Biological Transport↗

Haematological toxicity of carboplatin and cisplatin combined with whole body hyperthermia in rats.

Acute haematological toxicity induced by cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) (carboplatin) and cis-diamminedichloroplatinum (II) (cisplatin) in combination with whole body hyperthermia (WBH) (2 h at 41.5 degrees C) was examined using a F344 rat model. The thermal enhancement ratios (TERs) of drug-mediated thrombocytopenia, anaemia and leukopenia were determined from the dose-response curves of the nadir values of the peripheral platelet, RBC and WBC counts. Carboplatin produced profound depression of platelet counts which was over three-fold greater than cisplatin (14% vs 51% of the control), while the decrease in WBC and RBC counts induced by carboplatin did not differ significantly from those observed with cisplatin. These carboplatin or cisplatin-mediated haematological toxicities were significantly enhanced by WBH. The depth of decrease in platelet, RBC and WBC counts induced by the maximum tolerated dose (MTD) of carboplatin (30 mg kg-1) combined with WBH was identical to that induced by the MTD of carboplatin (70 mg kg-1) alone. The TERs of carboplatin-mediated thrombocytopenia, anaemia and leukopenia were 2.0, 2.8 and 1.9, respectively. The thermal enhancement of cisplatin mediated haematological toxicity was similar to that of carboplatin, with TERs of 1.8 for thrombocytopenia, 2.4 for anaemia and 1.9 for leukopenia. These data, demonstrating thermal enhancement of cisplatin or carboplatin-mediated haematological toxicity, must be taken into account in the clinical application of the combination therapy of platinum and WBH.

Anemia↗

Transgenic Drosophila carrying mammalian cytochrome P-4501A1: an application to toxicology testing.

Transgenic Drosophila which carry a canine cytochrome P-450 were established and evaluated for its value on toxicology testing. Dah1, a cDNA clone for the canine hepatic P-4501A1, was ligated between the promoter of Drosophila heat-shock protein gene and the terminator of actin 5C gene, and then microinjected into Drosophila embryos with a transposon P element. The injected DNA was stably integrated into chromosomal DNA in germ line cells. After heat-shock treatments, transgenic larvae produced mRNA and a detectable amount of protein that cross-reacted with antibodies against rat P-4501A1. The ability of transgenic flies to activate procarcinogens was monitored in the DNA repair test with the endpoint being preadult mortality of repair-defective mei-9a mei-41D5/Y males. Heat-shock treatments of larvae showed that the repair-defective males carrying the P-4501A1 transgene were killed by lower concentrations of 7,12-dimethylbenz[a]anthracene than their non-transgenic or non heat-shocked counterparts. Coadministration of alpha-naphthoflavone, one of the inhibitors of P-4501A subfamily, cancelled the enhanced mortality of transgenic males, supporting that 7,12-dimethylbenz[a]anthracene was metabolized to its genotoxic form by the expressed P-4501A1 enzyme. This study indicates a potential utility of transgenic Drosophila for screening mammalian promutagens and procarcinogens.

9,10-Dimethyl-1,2-benzanthracene↗

Late radiographic findings after anterior cervical fusion for spondylotic myeloradiculopathy.

A retrospective study was performed to evaluate the radiographic changes that occurred at spinal levels adjacent to fused vertebrae after anterior cervical fusion. One hundred six patients with cervical spondylotic myeloradiculopathy (88 men, 18 women) were followed for an average of 8.5 years. The average age at follow-up was 64 years. Forty-two patients underwent a single-level fusion, 52 had a two-level fusion, and 12 had three levels fused. Seventeen patients who underwent additional surgery after anterior fusion also were reviewed, with an average follow-up period of 2.9 years. Postoperatively, cervical flexion-extension resulted in significantly increased movement about the vertebral interspace at the upper adjacent level. An increment of posterior slip of the vertebra immediately above the fusion level, with associated spinal canal compromise of less than 12 mm, significantly affected neurologic results. Patients with multilevel fusions notably exhibited these radiographic abnormalities at adjacent levels. Spinal canal stenosis, when associated with dynamic spinal canal stenosis in the vertebra above the fusion level, affected late neurologic results. Results of salvage laminoplasty were not satisfactory. Unnecessarily extended longer fusion must be avoided.

Cervical Vertebrae↗

Calcium crystal deposition in the ligamentum flavum of the cervical spine.

This article reports eight patients who underwent posterior decompressive surgery for myeloradiculopathy caused by calcium crystal deposition in the ligamentum flavum of the cervical spine. All were women with an average age of 72 years and showed neurologic improvement postoperatively. Four patients had diabetes mellitus, and knee meniscus calcification on radiographs were noted in four patients. The ligamentum flavum of C5-6 and C6-7 were sites frequently involved. Crystallographic examination confirmed resected deposits as calcium pyrophosphate dihydrate crystal in all patients and additional hydroxyapatite crystal in two. Histology confirmed marked degeneration in elastic fibers about the calcium deposits. This pathologic condition is possibly spinal manifestation of systemic calcium crystal deposition disease.

Aged↗

Acute effect of topical carteolol on ocular pulsatile volume change.

To determine whether topical carteolol affects ocular blood flow, we studied effects of carteolol 2% on the ocular pulse waves in 9 normal volunteers, and analyzed the results as variations in pulsatile volume changes (PVC) for one minute (PVCm) using the Friedenwald's pressure-volume relationship. PVC means a volume for the pressure amplitude in each pulse. The pulse waves were recorded with a pneumatonometer and analyzed by a computer. The PVCm change 15 min after the carteolol instillation was evaluated with the control performed with biological salt solution in the same manner. The data showed a net increase in the PVCm of the carteolol-instilled eyes (21.3 +/- 6.4 microliters/min: mean +/- standard error, p < 0.05, paired t-test). Considering a finding that PVCm takes 50% of the total ocular blood flow, the results suggest a possible alteration in the total flow by a carteolol instillation.

Administration, Topical↗

Individual and combined effects of intact PTH, amino-terminal, and a series of truncated carboxyl-terminal PTH fragments on alkaline phosphatase activity in dexamethasone-treated rat osteoblastic osteosarcoma cells, ROS 17/2.8.

The individual and combined effects of intact PTH, amino-terminal, and a series of truncated carboxyl-terminal PTH fragments on alkaline phosphatase activity were examined in dexamethasone-treated rat osteoblastic osteosarcoma cells ROS 17/2.8. Dexamethasone-induced alkaline phosphatase activity was inhibited not only by hPTH(1-84) and amino-terminal PTH fragment hPTH(1-34), but also by carboxyl-terminal PTH fragment hPTH(69-84) in a dose-related fashion. At 10(-7) mol/l, hPTH(1-84) completely abolished dexamethasone-induced alkaline phosphatase activity, while hPTH(1-34) and hPTH(69-84) reduced alkaline phosphatase activity to 0.16 +/- 0.02 and 0.80 +/- 0.03 fold, respectively, of the control value obtained in the absence of PTH peptides. The combination of hPTH(1-34) and hPTH(69-84) resulted in reduction of alkaline phosphatase activity to the level obtained by hPTH(1-84). The shorter carboxyl-terminal PTH fragment hPTH(71-84) did not affect alkaline phosphatase activity or modulate the action of hPTH(1-34). The longer carboxyl-terminal PTH fragment hPTH(53-84) stimulated alkaline phosphatase activity up to 1.23 +/- 0.03 fold and partially blunted the inhibitory effect of hPTH(1-34) on alkaline phosphatase activity. These findings suggest that carboxyl-terminal PTH fragments could exert diverse effects on the target cells, depending on the length of deletion of amino-terminal amino acids of PTH molecule, and interact with amino-terminal PTH fragment. The two amino-terminal amino acids of hPTH(69-84) and the 53-68 portion of hPTH(53-84) might be responsible for the respective inhibitory and stimulatory effects of the peptides on alkaline phosphatase activity.

Alkaline Phosphatase↗

Early carcinoma of the stomach.

We analyzed data on 423 Japanese patients with early carcinoma of the stomach with respect to clinicopathologic features and prognosis. All patients were treated in the clinics at which we work. The upper one-third of the stomach was less frequently involved. Therefore, partial gastrectomy was performed more often in patients with early carcinoma of the stomach than in those with advanced carcinoma of the stomach. The differentiated type of carcinoma of the stomach was more frequent and grew expansively. Lymph node metastasis was noted in 11.6 percent of the patients, lymphatic vessel involvement was evident in 13.5 percent and extensive lymph node dissection (R2 or R3) was performed in 86.0 percent. The 15 year survival rate for patients with early carcinoma of the stomach was 89.0 percent. Lymph node metastasis, differentiated tumor type and patient age proved to be independent prognostic factors, as determined by multivariate analysis. Increased detection of early carcinoma of the stomach in its curable stages may be achieved through gastrointestinal series and endoscopy for symptomatic patients. A close follow-up evaluation is essential to detect recurrences, even when a curative resection is performed.

Female↗

Pharmacokinetic and pharmacodynamic study of amodiaquine and its two metabolites after a single oral dose in human volunteers.

The pharmacokinetics of amodiaquine (AQ, Flavoquine, CAS 6398-98-7) and its metabolites, mono (AQml) and bis-desethyl amodiaquine (AQm2) were investigated in 8 healthy volunteers after an oral dose of 306.2 mg of AQ. Metabolic clearance was the main AQ elimination pathway. AQ disappeared rapidly, from the plasma and blood, whereas AQml appeared rapidly in keeping with a hepatic first-pass effect. By contrast, AQ was little excreted in urine and AQm2 formation from AQm1 was low. Blood AQm1 concentrations were higher than plasma levels, with an AQm1/AQ concentration ratio of 5 to 10. This result was related to strong uptake of AQm1 by white blood cells, as shown by an in vitro study. On the basis of plasma concentrations, there was no preferential uptake by red blood cells, the pharmacological target cells; effective AQ concentrations should thus be analyzed in plasma rather than in whole blood. The inhibitory activity of patients' sera on Plasmodium falciparum growth in vitro appears to be directly related to the AQm1 concentration.

Adult↗