Why does a difference in growth rate between rats of the Wistar and Sprague Dawley strains occur when a niacin-free and tryptophan-limiting diet is fed?
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Biomedical subjects
Publications and source records attributed to K Shibata.
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We recorded spinal cord evoked potentials (SCEPs) and spinal somatosensory evoked potentials (spinal SEPs) in 30 operations following stimulation of the epidural spinal cord and the peripheral nerve, respectively, to compare their feasibility as an intraoperative technique for spinal cord monitoring. SCEPs produced quicker responses and had larger amplitudes with simpler waveforms. SCEPs could reflect residual function of the pathological spinal cord and predict the postoperative clinical outcome, findings which are not observed with spinal SEPs. Moreover, SCEPs had a much higher sensitivity to spinal cord insult. Therefore, we conclude that the SCEPs were more appropriate indicator than the spinal SEPs as an intra-operative monitoring method for spinal cord function.
In the clinical application of hyperthermia, determining the thermotolerance that influences the anti-tumor effect is an important problem. The purpose of this study was to investigate the methods of induction and disappearance of thermotolerance in vivo. After transplanting MH134 cancer cells into the paws of C3H mice, local hyperthermia with warm water was administered, and the movement of thermotolerance in vivo studied in terms of the heating intervals and tumor growth times. When the first heating was applied on the 8th day after transplantation, thermotolerance appeared within 1 hour, increasing gradually to reach a maximum at 18 hours, after which it decreased gradually and disappeared after 48 hours. When the first heating was applied on the 13th day after transplantation, which fell during the rapid tumor proliferation period, the movement of thermotolerance presented a similar pattern of appearance and disappearance. The results of this study made it clear that there was no difference in the movement of thermotolerance between the two periods even though each had a different rate of tumor proliferation.
A 33-year old dentist developed fulminant hepatitis. At admission, a test for IgM antibody to hepatitis B core antigen (IgM anti-HBc) was positive, while tests for HBsAg and HBeAg were negative. He was cured of the disease, but in follow-up examinations from 1983 to 1990 IgM anti-HBc was continuously detected with radioimmunoassay while HBsAg and HBV-DNA were absent in the serum. However, HBcAg was found in a biopsied liver specimen and a small quantity of HBV-DNA was detectable by polymerase chain reaction assay. These observation suggest that the continuous detection of IgM anti-HBc without HBsAg in serum is due to persistent HBV infection and HBV replication in the liver.
The effect of tandospirone, a 5-hydroxytryptamine (5-HT)1A agonist/anxiolytic, injected directly into dorsal hippocampus, on Vogel-type conflict behavior in rats was investigated and the findings were compared with the effects of diazepam and zopiclone. Tandospirone (30 micrograms/2 microliters and 60 micrograms/2 microliters) and diazepam (40 micrograms/2 microliters) but not zopiclone (20 micrograms/2 microliters), produced a potent anticonflict action in rats. The anticonflict action of tandospirone (30 micrograms/2 microliters), injected into the dorsal hippocampus, was significantly blocked by (-)-propranolol (5 mg/kg i.p.). The present findings provide evidence that suggests that tandospirone has an antianxiety action, presumably by stimulating 5-HT1A receptors in the dorsal hippocampus.
The question as to whether reduction of plasma catecholamine concentration contributes to the beneficial effects of upper thoracic epidural anesthesia on survival during hemorrhagic shock was examined. Twenty-six dogs were anesthetized with halothane and nitrous oxide, and blood was withdrawn to reduce the mean arterial blood pressure (MAP) to 40 mmHg. The 12 dogs in group A received both upper thoracic epidural anesthesia before the hemorrhage and intravenous infusion of epinephrine (450 ng.kg-1.min-1) and norepinephrine (150 ng.kg-1.min-1) during hemorrhage. The 14 dogs in group B received none of these. At 20 min after the start of the bleeding, plasma catecholamine concentrations were increased in both groups more than ten-fold. There were no significant intergroup differences with respect to these concentrations at any point during the experimental period. During the 100-min period of hemorrhage, 1 of the 12 animals in group A and 10 of the 14 in group B died. A significant difference in survival was seen between the two groups over the 100-min hypotensive period (P less than 0.01 by the generalized Wilcoxon test). These results suggest that the survival benefit of upper thoracic epidural anesthesia cannot be explained simply by differences in the level of catecholamines in the plasma, and that perhaps differences in the level of catecholamines at the nerve endings or other factors may be more important.
The adherence of Serratia marcescens to bladder epithelial cells of mice with alloxan-induced diabetes was studied. S. marcescens adhered more strongly to the bladder epithelial cells of diabetic mice than to those of normal mice both in vitro and in vivo. The susceptibility of diabetic mice to urinary tract infection may be due to an increased adhesive capacity of bladder epithelial cells.
The solution conformations of novel dipeptides, methyl (2S, 3'S)-3-methyl-2-(2'-oxo-3'-isopropyl-1'-piperazinyl)-butanoate (EVV-OCH3), methyl (2S, 3'S)-3-phenyl-2-(2'-oxo-3'-benzyl-1'-piperazinyl) propionate (EFF-OCH3), and their derivatives (Boc-Gly-EVV-OH, Boc-Gly-EVV-Gly-OH, and Boc-Gly-EFF-OH), were studied by 1H NMR measurements and molecular mechanics calculations (1). The molecular structures of Boc-Gly-EVV-OH, Boc-Gly-EFF-OH, and the hydrochloride of EVV-OCH3 were determined by X-ray analyses. The conformations of the piperazinone rings and the side chains of these oligopeptides were clarified.
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NM394 is a new 6-fluoroquinolone antibacterial agent with a tricyclic structure which has a bridge that connects the N-1 and C-2 positions of the quinolone. The antibacterial activity of NM394 against clinical isolates of staphylococci, streptococci, enterococci, members of the family Enterobacteriaceae, and Pseudomonas aeruginosa was equal to or one-half that of ciprofloxacin. NM394 was as active as ofloxacin against gram-positive bacteria and was two to eight times more active against gram-negative bacteria, including P. aeruginosa. NM394 was two to eight times more active than enoxacin against gram-positive and gram-negative bacteria. The MICs of NM394 against Escherichia coli and P. aeruginosa at pH 5.5 were reduced 4 to 16 times compared with those at pH 7.0. Ciprofloxacin, ofloxacin, and enoxacin were 2 to 32 times less active against these two bacteria and Staphylococcus aureus at an acidic pH than they were at pH 7.0. In the presence of 5 mM Mg2+, the MICs of all of these drugs increased 2 to 32 times, but they were only slightly affected by 5 mM Ca2+, type of medium, serum, or size of inoculum. NM394 showed potent bactericidal activity and inhibited the supercoiling activity of E. coli DNA gyrase. The in vitro antibacterial profile of NM394 is similar to that of other 6-fluoroquinolones.
NM441 is a lipophilic prodrug of a new thiazeto-quinoline carboxylic acid derivative NM394, and when it is administered orally it is readily absorbed and hydrolyzed to its parent compound. After oral administration of NM441 at a dose of 20 mg/kg to dogs, the peak concentration of NM394 in plasma was 2.39 micrograms/ml, whereas it was 0.63 micrograms/ml for NM394 administered alone. The in vivo activity of NM441 was compared with those of ciprofloxacin, ofloxacin, and enoxacin in mouse protection studies. NM441 was as effective as ofloxacin and was twice as effective as ciprofloxacin against systemic infection with Staphylococcus aureus. Against infections with streptococci, NM441 was two to three times as effective as ofloxacin and five times as effective as ciprofloxacin. Against infection with Escherichia coli, NM441 was as effective as ciprofloxacin and ofloxacin, but against infections with Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa, NM441 was two to four times as effective as ciprofloxacin and ofloxacin. NM441 was three to seven times as effective as enoxacin in systemic infections. Against urinary tract infections with E. coli, NM441 reduced the number of bacterial CFU per gram of kidney by 1 to 2 log10 more and, with P. aeruginosa, by 1 to 6 log10 more than did ciprofloxacin and ofloxacin. Against respiratory tract infections with K. pneumoniae, NM441 was as effective as ofloxacin and was twice as effective as ciprofloxacin.
Conventional tomography has been criticized for its low contrast caused by scattered radiation and tomographic blur. The authors developed a digital tomosynthesis system as a substitute for conventional tomography. With the image processor in the system, two types of postprocessing can be performed to improve the quality of synthesized tomograms. One-dimensional spatial frequency filtering effectively reduces linear tomographic blur and enhances image information when an appropriate filter is used. Correction of structure mottle helps enhance the image clarity. The system allows reconstruction of tomograms at any desired depth and performance of tomosynthetic angiography and dual-energy subtraction. The system solves some of the problems associated with plain tomography and dual-energy subtraction and provides diagnostic clinical images.
The inhibitory effects of a prescription of herbal medicine, tentatively named P-3, were studied pathologically in an experimental model of the glomerular lesion induced by purified snake Agkistrodon acutus venom proteinase (Ac1-P) in mice. Ac1-P was intravenously inoculated at a single LD50 dose. In the treated group, mice were intraperitoneally injected with an extract of P-3 at a designated time once every two days from 2 days before to 1 week after Ac1-P inoculation. The control group mice were injected with saline instead of P-3. In the control group, the main pathologic changes within 48 hrs after inoculation were pulmonary and gastrointestinal tract hemorrhage and renal petechiae with hematuria. The kidney microscopically showed cystic transformation of the glomerular capillary tufts. followed by occlusive thrombosis. One week after inoculation, the glomerular lesions were mostly replaced by proliferative or proliferative-sclerosing changes with occasional crescent formation. Early signs of tubular atrophy accompanying the glomerular changes were observed. In the P-3 treated mice surviving 48 hrs and 1 week, the changes observed in the controls were markedly inhibited, although P-3 treated mice dying earlier than 30 hrs exhibited hemorrhagic changes similar to controls. This indicated that the herbal medicine had efficacy against the tissue injuries induced by Ac1-P as a proteolytic enzyme.
A 54-year-old female presented with apparent isolated hypothalamic histiocytosis X associated with diabetes insipidus and Korsakoff's syndrome. Computed tomographic and magnetic resonance imaging demonstrated a single hypothalamic mass. A craniotomy for biopsy found granulation tissue of unknown cause. Further investigation discovered genital bleeding before admission. Biopsy of the cervix uteri revealed histiocytosis X. Further studies showed the disease was restricted to the hypothalamus and the endometrium of the cervix uteri. Low-dose irradiation led to partial regression of the hypothalamic mass and improvement of Korsakoff's syndrome. Even when a diagnosis of isolated hypothalamic histiocytosis X is confirmed, the possibility of another histiocytosis X lesion in an unexpected region must be considered.
A rapid and convenient measurement of tryptophan in whole blood, serum, liver, brain, urine, and alkaline hydrolysates of proteins and foodstuff was done by high-performance liquid chromatography. The sample preparation was simply homogenized or mixed in a 5% trichloroacetic acid solution and a sample of the supernatant was injected onto a column after filtration with a 0.45-micron filter. The method used a Chemcosorb 5-ODS-H column (particle size, 5 microns, 150 x 4.6 mm i.d.) eluted with 20 mM potassium dihydrogen phosphate (pH adjusted to 3.7 by the addition of phosphoric acid) containing 1 g/l of sodium heptane sulfonate and 3 mg/l EDTA.2Na-acetonitrile (93:7, v/v) at a flow rate of 1.5 ml/min. The tryptophan contents in whole blood, serum, liver, and brain were electrochemically estimated at +1000 mV vs. Ag/AgCl, the detection limit being 0.2 pmol (40.84 pg) at a signal-to-noise ratio of 5:1. The tryptophan contents in urine, proteins, and foodstuff were fluorometrically estimated with an excitation wavelength of 280 nm and with an emission wavelength of 340 nm, the detection limit being 20 pmol (4.08 ng) at a signal-to-noise ratio of 5:1. Tryptophan was eluted at about 10.5 min. The total analysis time was about 12 min.
Three monoclonal antibodies, designated FP-1, FP-2 and FP-3, were obtained by immunizing a BALB/c mouse with dispersed human fetal pancreatic cells and using hybridoma technology. FP-1, FP-2 and FP-3 reacted specifically, respectively, with the ductal epithelial, acinar and islet cells, of the fetal pancreas as well as with adult human pancreatic tissue, suggesting a use in the discrimination of pancreatic cell types. Upon screening various tumor tissues, FP-1 was found to react with adenocarcinomas of the pancreas (16/23), stomach (7/8), colon (4/6) and gall bladder (2/2) as well as with the three malignant cell lines, PANC-1 (pancreas), HT-29 (colon) and LoVo (colon). In contrast to FP-1, FP-2 and FP-3 reacted with only 5% (2/39) and 0% (0/39), respectively, of these adenocarcinomas. Although FP-3 did not react with any of these adenocarcinomas, it did react with various APUDoma cells such as islet cell tumors of the pancreas (3/5), pheochromocytomas (2/2), medullary thyroid carcinomas (2/3) and gastrointestinal carcinoids (1/3). FP-3 thus appears to be the first monoclonal antibody with extremely high endocrine cell specificity.
We report a patient with serious organophosphorus-induced delayed neurotoxicity due to malathion. The patient was a 49-year-old male with a history of habitual alcohol drinking, who ingested approximately 100 ml of 50% malathion [S-1,2-bis(ethoxycarbonyl)-ethyl-0,0-dimethyl phosphorodithioate solution], with a large amount of alcohol in a suicide attempt. Following recovery from an acute cholinergic phase 36 hours after ingestion, respiratory muscle weakness, consciousness disturbance and diffuse weakness of the limb muscles occurred, necessitating mechanical ventilation. On the 7th hospital day, glove and stocking type sensory disturbance was observed and weakness of the limbs had progressed to distal dominant flaccid quadriparalysis with moderate muscle atrophy. Two months after onset, neurogenic bladder and spinal automatism became obvious. After 7 months, spasticity of the lower limbs developed, while the weakness of the upper limbs improved. Sural nerve biopsy showed axonal degeneration, loss of large myelinated fibers and increases in Schwann cell clusters. These findings were similar to those seen in patient with triorthocresyl phosphate (TOCP) intoxication. The symptoms of this patient seemed to correspond to Senanayake's "intermediate syndrome". The final clinical features and sural nerve biopsy findings were in close agreement with those in patients with serious organophosphorus compounds induced delayed neurotoxicity due to TOCP intoxication. However, this patient exhibited more severe neuropathy than seen in previously reported cases of organophosphorus compounds induced delayed neurotoxicity caused by less toxic organophosphorus compounds, such as Dipterex. This suggests that alcohol might have been an etiological factor in damage of nervous tissue in this rare case. This is the first case of organophosphorus compounds induced delayed neurotoxicity due to malathion to be reported in Japan.
A 46-year-old male was admitted to the Department of Neurology complaining of gait disturbance. He was given a diagnosis of Behçet's disease and placed on colchicine (0.5-1.0 mg/day) for 7 months without improvement. Subsequently cyclosporin (290 mg/day) was added this regimen. However, 7 months after initiation of combined colchicine/cyclosporin therapy serum creatine kinase (CK) rose to 1,255 U/l. On admission, neurological examination revealed generalized muscle atrophy with predominant proximal muscle weakness and decreased deep tendon reflexes. No myalgia was noted. Laboratory tests demonstrated anemia, liver dysfunction, chronic renal failure and an elevated serum CK level. The plasma cyclosporin concentration was 220 ng/dl, which is within therapeutic limits. Motor unit potentials in electromyography of bilateral quadriceps muscles were generally of short duration and reduced amplitude. A biopsy of quadriceps muscle showed variability in the size of type 2 fibers and scattered small vacuoles. Some of the vacuoles resembled rimmed vacuoles. These vacuoles were stained positively for acid phosphatase. Electronmicroscopy revealed that these vacuoles contained dense bodies, myeloid bodies, and glycogen particles. Collectively suggesting that these structures are autophagic vacuoles. Cyclosporin was reduced to 200 mg/day with unchanged colchicine dose and bromocriptine, which potentiates cyclosporin effects, was started. Gradual recovery from muscle weakness ensued. These findings suggest that cyclosporin contributed to the pathogenesis of this myopathy. On increase in use of cyclosporin, one should consider the possibility of myopathy as one of its side effects especially in combination therapy with myotoxic drugs such as colchicine.