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Biomedical subjects

T Higuchi

Publications and source records attributed to T Higuchi.

At least 19 recordsLinked to original sources

Activation of paraventricular neurosecretory cells by local osmotic stimulation of the median preoptic nucleus.

Both electrical and local osmotic stimulation of the median preoptic nucleus (MnPO) predominantly produced excitation of paraventricular (PVN) neurosecretory cells in the rat. By contrast osmotic stimulation of the medial septal region was without effect, although electrical stimulation excited most cells. The results suggest that the MnPO is one of the osmosensitive sites controlling electrical activity of PVN neurosecretory cells.

Action Potentials

Collisionally induced dissociation in the study of A-ring hydroxylated vitamin D type compounds.

Collisionally induced dissociation (CID) is often used to determine the structure of ions based on comparison with the CID spectra of known ions. The latter are generated from judiciously selected compounds taking into account basic principles of ion chemistry. We report here on the use of this approach toward determination of the site of A-ring hydroxylation of vitamin D. Although not intrinsically an aromatic compound, vitamin D gives rise in its mass spectrum to an aromatic methylstyryl cation at m/z 118. A-ring hydroxylated metabolites of vitamin D would thus incorporate the extra OH group on the ion at m/z 118, shifting it to m/z 134. The position of substitution of the extra OH group on a metabolite could then be ascertained by comparing the CID spectrum of its m/z 134 fragment to those of the four possible (hydroxymethyl)styryl cations generated from synthesized authentic compounds. Because of their propensity to polymerize, these cations were generated in situ via the McLafferty rearrangement of the corresponding (hydroxyphenyl)ethanols. For optimum differentiation of isomeric ions, preparation of permethylated derivatives of vitamin D was necessary. The validity of the hypothesis was verified using 1,25-dihydroxy-vitamin D3 as a test compound. This method provides a viable approach for the characterization of A-ring hydroxylated metabolites of vitamin D as well as for related aromatic compounds.

Binding Sites

Estrogen fails to reduce tuberoinfundibular dopaminergic neuronal activity and to cause a prolactin surge in lactating, ovariectomized rats.

The activity of tuberoinfundibular dopaminergic (TIDA) neurons was estimated by measuring the concentrations of dihydroxyphenylacetic acid (DOPAC) in the median eminence of ovariectomized lactating rats, ovariectomized non-lactating female rats and castrated male rats in correlation with the estrogen-induced prolactin (PRL) surge. PRL surge with a peak at 17.00 h was observed in ovariectomized non-lactating rats but not in the other groups. DOPAC levels were significantly lower at 17.00 h than at 11.00 h in non-lactating female rats, but there was no change of DOPAC levels in lactating rats and male rats. These results indicate that TIDA neuronal activity is inhibited at the time of estrogen-induced PRL surge and that the TIDA neurons may alter their function to result in refractoriness of PRL response to estrogen in the lactating rat.

3,4-Dihydroxyphenylacetic Acid

1H spectroscopic imaging of rat brain at 7 tesla.

1H magnetic resonance spectroscopic imaging has been used to obtain metabolite maps of the rat brain. The spin-echo-based technique has been evaluated with respect to water and lipid suppression and sensitivity. Metabolite maps were constructed for choline, creatine + phosphocreatine, amino acids, N-acetyl aspartate, and lactate. A spatial resolution of 3 x 3 mm (in plane) with 7-mm-thick slices was achieved routinely in 60-min (16 x 16 phase encodings) acquisitions. For higher intensity resonances, metabolite maps could be constructed in as little as 10 min. Results from phantoms and from rats under normal and focal ischemia conditions are presented.

Amino Acids

The area postrema is not involved in osmotic activation of neurosecretory cells in the supraoptic nucleus.

Experiments were performed to examine whether or not the area postrema (AP) is involved in the osmotic control of neurohypophysial hormone release. In control rats and in rats bearing extensive lesions of AP, extracellular action potentials were recorded from neurosecretory cells in the supraoptic nucleus (SON) and firing rates determined before and after the intraperitoneal (i.p.) injection of 1.5 M-NaCl solution. Lesion of the AP significantly (p less than or equal to 0.05, Mann-Whitney's U-test) lowered firing rate of putative vasopressin (phasic) cells but not that of oxytocin (non-phasic) cells. In lesioned animals, i.p. injection of hypertonic saline, however, caused similar changes in plasma osmotic pressure, plasma oxytocin concentration and mean firing rates of both putative oxytocin and vasopressin cells to those in control rats. The results suggest that the osmotic control of SON neurosecretory cell activity in the rat can take place in the absence of the AP.

Animals

The effectual level of ursodeoxycholic acid in therapy for non-advanced chronic cholestasis is fifty percent of total serum bile acids.

Ursodeoxycholic acid therapy (600 mg/day) was evaluated in twelve patients with non-advanced chronic cholestasis. Within four months, ursodeoxycholic acid replaced more than 50% of total bile acids in 8 patients and the reduction of serum gamma-glutamyltranspeptidase, alkaline phosphatase and transaminases averaged 30% or more. The serum levels of chenodeoxycholic acid depend on those of ursodeoxycholic acid, but are not related to those of biochemical parameters. Drug therapy was continued in three poor responders for 2-3 four-month periods. In one case an increase of the serum proportion of ursodeoxycholic acid was associated with a reduction in biochemical parameters. The other two cases had high serum levels of chenodeoxycholic acid and/or cholic acid throughout the entire course of treatment. While the treatment of chronic cholestasis requires an effectual serum proportion of ursodeoxycholic acid, it is important to distinguish endogenous persistent hyper-bile-acidemia from ursodeoxycholic acid-related acidemia.

Adult

Lesion and electrophysiological studies on the hypothalamic afferent pathway of the milk ejection reflex in the rat.

The afferent pathway of the milk ejection reflex in the hypothalamus was investigated with lesion and electrophysiological methods in anesthetized lactating rats. Destruction of the central region of the mid-hypothalamus (n = 12) blocked milk ejections induced by suckling, while that of the lateral region (n = 7) had no effect. In an electrophysiological study, extracellular recordings of neurons antidromically activated by electrical stimulation of the supraoptic nucleus were obtained from the ipsilateral hypothalamus caudal to the paraventricular nucleus (n = 84). Thirty-nine neurons were examined to see whether their firing activities changed during the milk ejection reflex. A group of 13 neurons were found to show changes in their activities prior to the reflex milk ejection; the neurons displayed a brief high-frequency burst of spikes before each milk ejection in the same manner as oxytocin neurons, and none of them antidromically responded to electrical stimulation of the neurohypophysis. The bursting neurons were recorded from the dorsomedial hypothalamic nucleus (n = 6), the region just lateral to that nucleus (n = 3) and the posterior hypothalamus (n = 4). The locations were included in a region whose destruction blocked the milk ejection reflex. These results indicate that the afferent pathway of the milk ejection reflex in the rat runs through the medial portion of the hypothalamus posterior to the paraventricular nucleus and that this region contains neurons which relay the input to the oxytocin neurons projecting in the neurohypophysis.

Afferent Pathways

Three-dimensional 1H spectroscopic imaging of cerebral metabolites in the rat using surface coils.

Three dimensional metabolite maps of protonated metabolites were obtained using 1H magnetic resonance spectroscopic imaging at 7 T. Surface coils were used to increase sensitivity and spatial resolution significantly over a volume coil two-dimensional acquisition. Adiabatic pulses were employed to provide homogeneous B1 excitation and frequency selective refocusing over the volume of the rat brain. These techniques were employed to obtain three-dimensional spectroscopic imaging spectra from nominal voxel volumes of 9-30 microliters from rat brain. The improved spatial resolution and sensitivity are also demonstrated with studies of focal ischemia in the rat.

Animals

Hepatic resection is not enough for hepatocellular carcinoma. A follow-up study of 92 patients.

We followed up 92 patients who underwent curative hepatic resection for hepatocellular carcinoma between 1982 and 1991. The long-term survival rates for these 92 patients for 1, 3, and 5 years were 98.8, 81.6, and 57.3%, respectively. As of May 1991, the carcinoma had recurred in 52 patients (56.5%). Recurrent tumors usually occurred in the residual liver within 3 years after surgery but were not always located near the primary lesion. The biologic characteristics of the primary tumors, such as serum alpha-fetoprotein, tumor size, number of tumors, and portal involvement, were closely related to recurrence and long-term survival. However, the type of hepatectomy performed on the primary tumor had little influence on recurrence or long-term survival. We conclude that recurrence cannot be avoided by hepatic resection alone, much less with limited resection; postoperative positive adjuvant therapy is required to prevent recurrence for patients with satellite nodule and/or portal involvement.

Adolescent

Circadian variation in R-THBP-induced enhancement of the ambulation-increasing effect of methamphetamine on mice.

6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP), a co-factor for tyrosine hydroxylase and tryptophan hydroxylase, induces the enhancement of ambulation-increasing effect of methamphetamine on mice. In this study, we investigated the circadian variation in the interaction between R-THBP and methamphetamine by changing the time-of-day of both methamphetamine administration and pretreatment with R-THBP. The mouse's ambulatory activity was measured by a tilting-type activity cage for 4 hr. In the daytime, but not in the nighttime, the ambulation-increasing effect of methamphetamine (1 and 2 mg/kg, s.c.) was significantly enhanced by the pretreatment with R-THBP (100 mg/kg, s.c., 2 or 6 hr before). These data indicate the possibility that peripherally administered R-THBP increases the biosynthesis of catecholamine especially in the daytime.

Analysis of Variance

Abolition of prolactin surge induced by ovarian steroid hormones in the lactating rat.

There are data indicating that stress-induced prolactin (PRL) release is blunted in the lactating rat like the release of other stress-associated hormones. In this experiment, the PRL release evoked by administration of estrogen, which is another principal stimulus for PRL release, was examined in ovariectomized lactating rats 8-15 days after delivery. Estradiol benzoate (EB, 20 micrograms) injections into ovariectomized nonlactating rats induced a PRL surge starting between 13:00 and 15:00 h with a peak at 17:00 h 2 days after the treatment, whereas the EB-induced PRL surge was absent in ovariectomized lactating rats separated from their pups at 09:00 h on the day or in mothers without separation from their pups. Injection of either thyrotropin-releasing hormone (TRH; 10 micrograms/kg) or pimozide (0.5 mg/kg) elevated serum PRL concentrations similarly in lactating and nonlactating rats when examined just before the beginning of the expected estrogen-induced PRL surge. Thus, the main cause for the reduced PRL response to estrogen in lactating rats seems not to be in the pituitary gland but in the brain. Progesterone, which is known to induce a PRL surge in ovariectomized estrogen-primed rats by acting on the mediobasal hypothalamus, also failed to evoke a PRL surge in lactating rats. Recovery from the inhibitory influence of suckling on PRL response to EB followed a time course similar to that observed in response to immobilization stress or to morphine injection; estrogen-induced PRL surge started to recover at 6 days and was almost fully recovered 8 days after weaning.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Influence of prostaglandin E1 on slight proteinuria in non-azotaemic diabetics.

In an investigation into the effect of prostaglandin E1 on proteinuria in nephrotic diabetic nephropathy, five patients were treated with 40 micrograms prostaglandin E1 administered intravenously over 2 h twice daily for 4 weeks. The following parameters were compared before and after treatment: protein excretion in urine; total serum protein concentration; serum albumin concentration; creatinine clearance; blood urea nitrogen; and serum creatinine content. A further five patients with nephropathy resulting from non-insulin-dependent diabetes mellitus were selected as controls. Analysis of the results using Student's t-test showed no significant change in any of the parameters before and after treatment.

Adult

Enhancing effect of sodium chloride on in vitro adsorption of paraquat onto activated carbon.

The enhancing effect of sodium chloride addition on the adsorption of paraquat onto activated carbon was discussed from the standpoints of equilibrium amount adsorbed and adsorption rate in vitro. The amount of paraquat adsorbed was increased by the addition of sodium chloride. The amount adsorbed with 0.1% addition was about five times greater than that in sodium chloride-free solution at an equilibrium concentration of 1 mg/L. The adsorption rate of paraquat onto activated carbon was also accelerated by sodium chloride addition. Kinetic constants in 0.1% and 0.9% sodium chloride solution were about 1.4 and 2.0 times greater, respectively, than that in sodium chloride-free solution. It was confirmed that paraquat removal by activated carbon was enhanced by sodium chloride addition. The reason was assumed to be the interrupted dissociation of paraquat in solution caused by sodium chloride addition.

Adsorption

An evaluation of analyzed data of hemoglobin derivatives by CO-Oximeter in medico-legal autopsy.

We examined blood samples of autopsy cases by a CO-Oximeter and evaluated the data for investigation of death including asphyxia. When sampling methods were examined, oxyhemoglobin (O2-Hb) concentrations increased, and reduced hemoglobin (R-Hb) concentrations decreased, by the contact of the blood with the air, while carboxyhemoglobin (CO-Hb) and methemoglobin (Met-Hb) concentrations appeared to be unchanged. The CO-Hb concentrations in the left heart blood were higher than those of the right. In the cases of death due to cold exposure, O2-Hb concentrations of the left heart blood were prominently higher than those of the right. In the cases of death in house fires and the asphyxiated, O2-Hb concentrations were extremely low (below 10%) in both of the left and right heart blood.

Asphyxia

[Structures of isomers of ursodeoxycholic acid: 3 beta,7 alpha- and 3 beta,7 beta-dihydroxy-5 beta-cholan-24-oic acids].

Isomers of ursodeoxycholic acid, 3 beta,7 alpha- and 3 beta,7 beta-dihydroxy-5 beta-cholan-24-oic acids (3 beta 7 alpha U and 3 beta 7 beta U) crystallize in the orthorhombic space group P2(1)2(1)2(1) containing one molecule and in the monoclinic group P2(1) containing two independent molecules in an asymmetric unit. The cell dimensions are a = 28.032(17), b = 9.973(5), c = 8.049(6) A for 3 beta 7 alpha U, and a = 11.771(8), b = 27.999(12), c = 6.637(2) A, beta = 90.78(6) degrees for 3 beta 7 beta U, respectively. Both structures were solved by the direct method and refined to the residual values of 0.065 (3 beta 7 alpha U) and 0.059 (3 beta 7 beta U). The conformations of the D rings of each molecule are different from each other: 3 beta 7 alpha U intermediate, 3 beta 7 beta U (A and B) half-chair form. In the crystal, 3 beta 7 alpha U molecules are connected by a hydrogen bond extended nearly parallel to the bc plane and 3 beta 7 beta U molecules are connected by the helical hydrogen bond system or by the zigzag one parallel to the ac plane.

Molecular Conformation

[Studies on the glucose tolerance and the endocrine function of the pancreas in primary sclerosing cholangitis].

The responses of serum IRI, serum IRG, and blood sugar levels to 75 g oral glucose and serum IRI to glucagon injection were investigated in 26 chronic hepatitis, 20 liver cirrhosis, 5 primary sclerosing cholangitis (PSC) and 8 healthy volunteers served as controls. The results obtained herein were as follow: 1) The frequency of the glucose intolerance in PSC was higher than the other liver diseases. The mean values of the insulinogenic index (delta IRI/delta BS 30 min) in PSC was lower than control subjects. No suppression of IRG by glucose was observed in PSC. 2) The maximum IRI value (max delta IRI) in PSC during glucagon test was lower than that in control subjects. 3) In one case of 5 PSC ICSA was founded to be positive. These data suggest that we should pay much attention to suffering from diabetes mellitus in natural history of PSC.

Aged

Factors affecting acetohexamide reductase activities in microsomes and cytosol from the kidney of male rats: age and castration.

Acetohexamide reductase activity in microsomes from the kidney of male rats increased markedly at puberty to approach the maximum level at 8 weeks of age; it was not detected until 4 weeks of age. Furthermore, castration suppressed effectively the activity in kidney microsomes at 8 weeks of age. These findings clearly indicate that the activity in kidney microsomes can be regulated by androgens. On the other hand, in cytosol from the kidney of male rats, a higher acetohexamide reductase activity was observed at all weeks of age tested. Castration had no significant effect on the activity in kidney cytosol.

Aging