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Biomedical subjects

H Baba

Publications and source records attributed to H Baba.

At least 19 recordsLinked to original sources

Flavone acetic acid increases the antitumor effect of hyperthermia in mice.

The combined effects of flavone acetic acid (FAA), a synthetic flavonoid, and hyperthermia on B16 melanoma cells were investigated. In vitro, FAA alone at concentrations below 100 micrograms/ml was not cytotoxic with a 60-min exposure at 37 degrees C. Hyperthermia at 43 degrees C for 60 min enhanced the cytotoxicity of FAA only at concentrations over 100 micrograms/ml. Inhibition of the growth of B16 melanoma solid tumor by FAA and/or hyperthermia was examined in vivo. FAA (100-200 mg/kg) inhibited tumor growth in a dose-dependent manner. The combined treatment of FAA (200 mg/kg) and hyperthermia (43 degrees C, 15 min) significantly inhibited tumor growth compared to a treatment of FAA or hyperthermia alone. The maximum antitumor effect of FAA combined with hperthermia was obtained when FAA was administered 2 or 4 h before heat. The significantly increased cytotoxicity of FAA combined with hyperthermia seems to relate to specific decreases in tumor blood flow, a reduction in tumor pH, and an increased tumor temperature, without altering pH in the normal tissues. This combined treatment of FAA and hyperthermia warrants further study for treating subjects with solid tumors.

Animals

Interaction of nascent preproparathyroid hormone molecules with microsomal membranes.

To characterize the early steps in the interaction of nascent chains of preproparathyroid hormone (prepro-PTH) with the secretory apparatus, such truncated nascent chains still attached to ribosomes were tested for binding to microsomal membranes and cleavage by signal peptidase. Nascent chains of 114, 97, 88, 81, 70, and 59 residues were tested for their ability to bind tightly to membranes and to undergo signal sequence cleavage. Chains of 81 residues and longer bound tightly to the membranes and were cleaved by signal peptidase. The 88- and 81-residue precursors and their corresponding pro-proteins were less efficiently associated with the membranes than were the 114- and 97-residue precursors and their corresponding pro-proteins. The 70-residue chain bound to the membrane but was not cleaved. When this peptide was subsequently released from the ribosome with puromycin, it was cleaved by signal peptidase. The 59-residue chain bound only slightly to the microsomal membrane and was not cleaved by signal peptidase, even when the nascent peptide was released from the ribosome with puromycin. Thus the critical length for productive binding to microsomal membranes is between 59 and 70 residues; the length required for signal cleavage is between 70 and 81 residues.

Amino Acid Sequence

Prognostic factors for noncurative gastric cancer: univariate and multivariate analyses.

We performed univariate and multivariate analyses of possible prognostic factors related to postoperative clinical course of patients with advanced gastric cancer. Noncurative resection was done for 119 patients with hepatic metastasis, peritoneal seeding, extensive lymph node metastasis, or direct invasion to adjacent organs, either alone or in various combinations. In the univariate analysis, 6 of 17 items such as peritoneal seeding, lymphatic invasion, vascular invasion, mode of invasion, extent of lymphadenectomy, and width of serosal invasion significantly correlated to the prognosis. The multivariate analysis indicated that three inherent pathologic factors, mode of invasion, lymph node metastasis, and hepatic metastasis, and one treatment factor, extent of lymphadenectomy, were significant variables predictive of the prognosis and that the prognosis was expected to be very poor in cases of infiltrative type, nodal involvement to tertiary nodes, presence of hepatic metastasis, and lymphadenectomy less than R3. Prognosis in terms of the extent of lymphadenectomy shows that extensive lymphadenectomy (R3) proved to be significantly effective in prolonging survival time, even after noncurative gastrectomy. We recommend extensive lymphadenectomy to prolong survival time for such patients.

Adenocarcinoma

Noncurative resection for advanced gastric cancer.

Between 1965 and 1985, 489 patients with advanced gastric cancer who were treated with gastric resection and in whom tumor cells remained after the operation were defined as cases of a "noncurative resection." The clinicopathological features and prognosis of these patients were examined and two groups were prepared: locally advanced cancer and cancer with a distant metastasis. In locally advanced cancer cases, tumor cells remained in the neighboring organs, lymph nodes, and/or resected margins; in those with distant metastasis, peritoneal dissemination and/or liver metastasis were present regardless of whether or not the metastasis was removed, with or without locally noncurative factors. Serosal invasion was prominent and high rates of lymph node metastasis and lymphatic involvement were evident in both groups. The survival rate for patients with locally advanced gastric cancer was better than that of patients with distant metastasis (P < 0.01). Survival time in patients with locally advanced cancer can be lengthened by resecting all of the primary tumor and as much of the metastatic lesions as possible, even if the surgical management is "noncurative." Aggressive postoperative chemotherapy for patients with distant metastasis from a gastric cancer is to be recommended.

Aged

In vitro succinate dehydrogenase chemosensitivity of gastric carcinoma--relationship to DNA content.

Relationships between in vitro chemosensitivity and cell nuclear DNA content were investigated in malignant cells from 41 patients exhibiting advanced gastric carcinoma. The chemosensitivity was evaluated by measuring the succinate dehydrogenase (SD) activity in drug-exposed cancer cells and the DNA content was microspectrophotometrically determined. Following exposure of malignant tissue to carboquone (CQ) and cisplatin (DDP), the mean SD activity in cells displaying a relatively regular DNA distribution (type II) was significantly higher than that in those exhibiting a widely scattered DNA distribution (type IV; P less than 0.01 in CQ, P less than 0.05 in DDP). A similar tendency was recognized in cells that were treated with aclacinomycin A (ACR), Adriamycin (ADM), and mitomycin C (MMC). Such a decrease in SD activity in cells exhibiting a type IV pattern was remarkable, especially in cases undifferentiated adenocarcinoma. Mitotic counting analysis revealed a significantly higher value for DNA pattern type IV as compared with the findings for type II (P less than 0.01). These results demonstrate that gastric carcinoma displaying a high malignant potentially shows a better response to antitumor drugs. Adjuvant chemotherapy prescribed following drug-sensitivity testing should be effective against such tumors.

Adult

Effect of chemotherapy combined with caffeine for osteosarcoma.

Nine patients with osteosarcoma were treated by chemotherapy combined with caffeine and surgery. All primary tumors showed complete histological response to preoperative chemotherapy consisting of three intraarterial infusions of cisplatin and caffeine without/with doxorubicin and two systemic high-dose methotrexate combined with vincristine. Limb-salvage surgery was performed in eight patients with marginal procedure, which led to the preservation of good limb function. Below-knee amputation was done in one patient with calcaneal osteosarcoma. There has been neither local recurrence nor lung metastasis in seven patients with conventional osteosarcoma during a median follow-up period of 28 months. Lung metastases leading to death were observed in one patient with small-cell osteosarcoma despite complete destruction of the primary tumor by preoperative chemotherapy. Chemotherapy combined with caffeine administration deserves further extensive and large-scale study in osteosarcoma.

Adolescent

In vivo assessment of the metabolic alterations in glucagonoma syndrome.

Stable-isotope methodology and indirect calorimetry were used to evaluate metabolic abnormalities in a patient with glucagonoma syndrome manifested by 17% body weight loss, hypoaminoacidemia, and hyperglycemia. Energy expenditure (26 kcal/kg) was the same as that predicted by the Harris-Benedict equation. The rate of appearance (Ra) of intracellular leucine (2.70 mumol/kg/min), an index of protein breakdown, was normal, although the percentage of leucine flux oxidized (31%), an index of amino acid catabolism, was 50% greater than the normal mean value. Glucose Ra in plasma (12.9 mumol/kg/min), representing hepatic glucose production, and glycerol Ra in plasma (3.04 mumol/kg/min), a measurement of whole-body lipolysis, were 15% and 25% greater, respectively, than mean values found in normal volunteers. These results suggest that long-term alterations in energy, leucine, glucose, and lipid metabolism in patients with glucagonoma are minimal. However, small long-term metabolic alterations caused by glucagon excess, in conjunction with chronic negative energy balance, could be responsible for the weight loss, hypoaminoacidemia, and hyperglycemia observed in this patient population.

Adult

Comparison of constant infusion and flooding dose techniques to measure muscle protein synthesis rate in dogs.

The exact relationship between the constant infusion and flooding dose techniques for measuring fractional muscle protein synthesis (FMPS) rates was determined in anesthetized dogs during the postabsorptive period, using different isotopes of leucine as tracers. First, [1,2-13C]- and [U-14C]leucine were given simultaneously by prime-constant infusion for 5 h to establish that both isotopes gave comparable FMPS rate values. The tracers gave almost identical FMPS rates and the values obtained after 3 and 5 h were not different. Next, the constant infusion and flooding dose methods were compared in the same animal by first measuring FMPS rate with a prime-constant infusion of [U-14C]leucine, then with a flooding dose of 376 mumol/kg [1,2-13C]leucine. The flooding dose method gave FMPS rates that were markedly greater than the constant infusion values. Finally, the effect of a 376 mumol/kg leucine flooding dose on FMPS rate was assessed using the prime-constant infusion of [U-14C]lysine. The large dose of leucine decreased FMPS rate by approximately 50% because acid-soluble muscle lysine (precursor) specific activity increased while the rate of incorporation of labeled lysine into protein decreased. These results indicate that the flooding dose method gives FMPS rates that are markedly greater than those obtained with the constant infusion method and that the latter method is not valid when a large dose of leucine is given.

Animals

Metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil to 5-fluorouracil in partially hepatectomized rats.

Changes in the metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) to 5-fluorouracil (5-FU) were examined in the plasma, lung, liver, stomach, small intestine, spleen and kidney in two-thirds partially hepatectomized rats. Concentrations of tegafur and 5-FU in plasma and tissues were determined 30 min after injecting 100 mg/kg of tegafur via the tail vein. The 5-FU concentration in the plasma remained unchanged for the first 7 days after hepatectomy. The tissue level of 5-FU was higher in the liver and kidney than in other organs examined, but there were no changes in levels of 5-FU in each organ examined. Our observations support the proposal that the conversion of tegafur to 5-FU is maintained in partially hepatectomized rats.

Animals

Spinal cord evoked potentials in thoracic myelopathy with multisegmental vertebral involvement.

Spinal cord evoked potentials were recorded preoperatively from the thoracic epidural space after spinal cord stimulation in 20 patients with thoracic myelopathy with multisegmental vertebral involvement. Waveform abnormalities in spinal cord evoked potentials, namely, positive-going wave or decrease in amplitude, were observed in all cases. Abnormalities, especially in the first negative component of spinal cord evoked potentials, were recorded at the most compressed site in each case. Decrease in amplitude of more than 50% was noted frequently in moderately involved cases, whereas positive-going wave was elicited predominantly in cases of severe myelopathy. Spinal cord evoked potentials should provide information for determining the range of decompression in multisegmental vertebral involvement.

Adult

The carboxy-terminus of parathyroid hormone is essential for hormone processing and secretion.

The biological function of the carboxy-terminal portion of the PTH molecule is unknown. We hypothesized that the carboxy-terminus of PTH may be essential for hormone processing and secretion. To ascertain the potential role of the carboxy-terminus in transport through the secretory pathway, we constructed a series of carboxy-terminally deleted mutants of human preproPTH. PreproPTH and these truncated peptides were expressed in cell-free extracts and in acutely transfected COS 7 cells. Intact preproPTH(1-84) (115 residues) was processed to proPTH(1-84); the PTH was secreted very efficiently. In contrast, translocation across the membrane of the endoplasmic reticulum and signal sequence cleavage were mildly impaired for PTH(1-52) (83 residues), moderately impaired for PTH(1-40) (71 residues), and dramatically impaired for PTH(1-34) (65 residues). Subsequent cleavage of the prosequence and secretion from intact cells were also dramatically impaired for PTH(1-52) and undetectable for PTH(1-40) and PTH(1-34). We conclude that more than 65 residues are needed to cross the endoplasmic reticulum and that more than 83 residues are needed for efficient prosequence cleavage and secretion. Perhaps similar requirements for full transport through the secretory pathway explains why most secreted peptides are synthesized as long propeptides of at least 80 residues.

Animals

New actions of parathyroid hormone through its degradation.

Parathyroid hormone degradation is intimately connected with its action. By the action of the unique renal neutral cytosolic PTH ase, PTH is split into 1-34 and 35-84 fragments, and further into 35-70 and 71-84 fragments. Amino-terminal 1-34 peptide was found to participate in the autoregulation of PTH secretion, suppressing the intact PTH secretion both in vivo in humans and in vitro in the dispersed bovine parathyroid cells. C-terminal fragment 35-84 and N-terminal fragment 1-34 both suppress the alkaline phosphatase production by ROS 17/2.8 cells to a lesser extent than the intact PTH 1-84, and the sum of the effects of the two fragments approximately equaled that of the intact hormone. Fragments 35-70 and 71-84 were devoid of such activity. Intracellular free calcium of human vascular endothelial cells was raised by intact 1-84, lowered on the contrary by C-terminal 35-84 fragment, but fragments 1-34, 35-70 and 71-84 had no effect. Fragments generated by the actions, supporting the physiological significance of PTH degradation by its target cells.

Animals

Mechanism of relaxation induced by K+ and nicotine in dog duodenal longitudinal muscle.

Dog duodenal longitudinal muscle strips precontracted with bradykinin responded to K+ (10 mM) with a transient relaxation, which was abolished by tetrodotoxin and oxyhemoglobin, but not influenced by atropine, ouabain and apamin. The induced relaxation was suppressed by treatment with 10(-5) M NG-nitro-L-arginine (L-NNA) a nitric oxide synthesis inhibitor, but not by the D-enantiomer. The inhibitory effect was antagonized by L- but not D-arginine. High concentrations (20 mM or higher) of K+ produced a relaxation followed by a sustained contraction; nicardipine abolished the contraction, but did not alter the relaxation. Nicotine produced a contraction, which was converted to a relaxation by atropine. The relaxant response was abolished by tetrodotoxin, hexamethonium and oxyhemoglobin, but was unaffected by timolol and phentolamine. L-NNA suppressed the relaxation, and L-arginine reversed the inhibition. The addition of K+ (20 mM) increased the content of cyclic GMP in the strips, the effect being prevented by tetrodotoxin and L-NNA. These findings suggest that K+ selectively stimulates the nonadrenergic inhibitory nerve, whereas nicotine stimulates both the excitatory cholinergic and inhibitory nerves. Nitric oxide released from the inhibitory nerve appears to transmit information to duodenal smooth muscle by increasing the production of cyclic GMP.

Adenosine Triphosphate

Hyperamylasemia associated with lymphadenectomy in patients surgically treated for gastric cancer.

The influence of standard lymphadenectomy on the occurrence of damage to the pancreas was evaluated in 28 patients with gastric cancer, by analysing related serum and urine enzyme activities, pre- and postoperatively. Enzymatic evidence for pancreatic damage was related to the surgical procedure performed. Postoperatively, the patients treated by R2 gastrectomy had significantly increased levels of P-type amylase in the serum compared with findings in patients treated by R1 gastrectomy or bypass procedures. Conversely, the S-type amylase in both groups remained within normal limits during the study period. Pancreatic secretary trypsin inhibitor (PSTI) and phospholipase A2 (PLA2) proved to be less sensitive to pancreas damage caused by lymphadenectomy. The R2 patients with P-type hyperamylasemia had no major postoperative complications. Thus, while the standard R2 gastrectomy may well be a relevant factor associated with the occurrence of transient P-type hyperamylasemia, there seems to be no relation to major postoperative complications such as pancreatitis.

Adult

[On the problems of the antituberculous drug resistance].

In this part, we will discuss exclusively about the technique of measurement. It is desirable especially for the proportion method that two inoculations with the same doses give the same number of colonies and when diluted, the colonies decrease exactly parallel to it degree of dilution. But this ideal is not necessarily realized and especially the difference between the dilution of 10(-3) and 10(-4) mg/ml on the drug free medium and that of 10(-2) and 10(-3) on the drug containing medium is fairly remarkable: the former is not so large but the latter sometimes varies tremendously with the drugs and their concentrations. So it is necessary to use always two inoculations for all specimens and the resistance is calculated on the medium inoculated with the same doses, for that, colonies on the control must be countable and suitable number that is 50-300. Further too concentrated solution like 10(-2) mg/ml must not be used for the proportion method. The selection of the most suitable two dilutions is specially important for this method. Original one is 10(-3) and 10(-5). Unfortunately we did not follow this formula and at first we adopted the combination of 10(-3) and 10(-4), then 10(-2) and 10(-4) finally 10(-2) and 10(-3) which was the worst. Now we searched for the dilution which gave the suitable number of colonies from our several thousand cases and found that 10(-4) was the most excellent and gave this number in 63%, next 10(-5) in 14%, and then 10(-3) in 7.2%, 10(-2) in only 1.0%. With the combination of 2 solutions 10(-3) and 10(-5)--original one--was most excellent (94.8%) then 88.4% with 10(-4) and 10(-5). The combination of 10(-2) and 10(-3) was worst, it gave only 8.9%. As the proportion method demands the most strict procedures for all cases, it is necessary as simplify as possible, thus in every day practice, only the drugs most frequently used (3 or 4 drugs) and one concentration for each drug could be examined. Further we discussed on the difference between DH-SM and SM, direct and indirect method and problem of plug.

Antitubercular Agents

[Effects of timolol and carteolol on ocular pulsatile blood flow].

Effects of timolol (0.5%) and carteolol (2%) on ocular pulsatile blood flow (PBF) were studied in healthy adult volunteers. PBF was measured with the BFA system, analyzing the ocular pressure waves. Each drug was instilled in one eye and PBF was measured in both eyes before and fifteen minutes after the instillation. In each drug, the PBF change between the two measurements was evaluated with a control study, which was performed in the same manner with physiological saline solution. In the non-instilled eyes, both timolol (n = 6) and carteolol (n = 9) had no significant change on PBF. In the instilled eyes, timolol (n = 6) caused no significant change, whereas carteolol (n = 9) increased PBF significantly. The range of the BFA system measurement error was within 4.7 +/- 2.4 microliters/min (P = 95%). Taking the error into account in each instilled eye, timolol (n = 6) increased PBF in 3 eyes and decreased it in 3 eyes, while carteolol (n = 9) increased PBF in 7 eyes, did not change it in one eye and decreased it in one eye. It is thought the effect of carteolol to increase PBF may be explained by endothelium-dependent relaxing factor (EDRF).

Adult

A simple procedure for intrahepatic biliary drainage in patients with obstructive jaundice owing to a recurrence of cancer following reconstructive gastric surgery.

We designed a simple and reliable method of intrahepatic biliary drainage for patients with obstructive jaundice owing to a recurrent gastric cancer. This approach can be used for selected patients treated by partial gastrectomy and reconstructive surgery, using the Billroth II procedure and antecolic anastomosis. Anastomosis between the intrahepatic bile duct and the afferent jejunal loop is performed at the anterior edge of the liver, thus facilitating the prevention of recurrence of jaundice caused by tumor infiltration. Application of this technique led to a long-term palliation, control of the jaundice and a fairly normal life.

Adult