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Biomedical subjects

K Meguro

Publications and source records attributed to K Meguro.

At least 127 records · Page 7Linked to original sources

Age-dependent decrease in histamine H1 receptor in human brains revealed by PET.

Age-related changes in histamine H1 receptors were studied using [11C]pyrilamine or [11C]doxepin by positron emission tomography (PET). The frontal, parietal and temporal cortices showed age-related decreases in binding of approximately 13% per decade. In contrast, the thalamus showed no apparent decrease in binding during normal ageing because of its higher nonspecific binding. Post mortem studies also indicated that the nonspecific binding of [3H]pyrilamine in the thalamus was approximately 112% higher than that in the cortex. However, no significant decrease in histamine H1 receptors with age was observed by in vitro binding assays of autopsied human frontal cortex. Possible reasons are given for the larger effects of age observed in the PET study than in the in vitro post mortem binding study.

Adolescent↗

Mapping of histamine H1 receptors in the human brain using [11C]pyrilamine and positron emission tomography.

We have studied the characteristics of carbon-11 labeled pyrilamine as a radioligand for investigating histamine H1 receptors in human brain with positron emission tomography (PET). [11C]Pyrilamine is distributed evenly in proportion to cerebral blood flow at initial PET images. Later (after 45-60 min), 11C radioactivity was observed at high concentrations in the frontal and temporal cortex, hippocampus, and thalamus, and at low concentrations in the cerebellum and pons. The regional distribution of the carbon-11 labeled compound in the brain corresponded well with that of the histamine H1 receptors determined in vitro in autopsied materials. In six controls, the frontal and temporal cortices/cerebellum ratio increased during the first 60 min to reach a value of 1.22 +/- 0.071. Intravenous administration of d-chlorpheniramine (5 mg) completely abolished the specific binding in vivo in the frontal cortex and temporal cortex (cortex/cerebellum ratio, 0.955 +/- 0.015). The availability of this method for measuring histamine H1 receptors in vivo in humans will facilitate studies on neurological and psychiatric disorders in which histamine H1 receptors are thought to be abnormal.

Adult↗

Prevention of respiratory infections in elderly bed-bound nursing home patients.

A procedure to prevent silent aspiration, which results in frequent respiratory infections, was conducted on elderly bed-bound nursing home patients who suffered mainly from cerebral infarction and dementia. We cleaned the mouth with povidone iodine and kept them in a sitting position for 2 hr after each meal in order to restrict respiratory bacterial infection and to prevent aspiration of gastric juices, respectively. Patients with urinary tract infections were excluded from the present protocol. During the treatment for 103 days the number of febrile days was significantly decreased in the treated group compared with the control group, probably due to minimizing of respiratory infections.

Aged↗

[Bactericidal clothes protect against respiratory infections in the elderly patients].

In order to protect against infections in the elderly patients, bactericidal clothes were used. Ninety elderly patients were divided into two groups; the control group and the other group with bactericidal clothes. In period I neither group received particular treatment for three months and in period II only the treated group used bactericidal clothes for three months. The control group in period II used regular clothes throughout. Cause of fever (greater than 37 degrees C) extending more than 10 or 15 days were significantly lower in the treated group than in the control group. It was suggested that the bactericidal clothes reduce infections in elderly patients.

Aged↗

Malignant lymphoma of the central nervous system presenting with central neurogenic hyperventilation. Case report.

The case is described of a 72-year-old woman who presented with a progressive right hemiparesis and central neurogenic hyperventilation. Pathological and radiological studies revealed diffuse infiltration of a malignant lymphoma into the entire central nervous system and the upper spinal cord. The authors review 12 cases of tumor-induced central neurogenic hyperventilation and discuss the pathophysiology of this condition.

Aged↗

[Differentiating effect of oral administration of retinol palmitate (Chocola-A) for an aged AML (M3) with severe complications].

A 74 year-old woman, who had been diagnosed as AML (M3) in poor condition, was treated with Retinol Palmitate (Chocola-A, 150,000 unit/m2 per os, after informed consent. An increase of white blood cells (neutrophil) counts was observed after 7 days. After 4 weeks, WBC counts were increased to 20,700/microliters (neutrophil counts 6,400/microliters) Maturation tendency of leukemic cells was also proved in the bone marrow. In vitro studies showed that morphological differentiation was recognizable in cultured leukemic cells treated with 10(-6)M all-trans retinoic acid after 6 days, but not in controls. Responses in the NBT reduction test were slightly less than in the clinical study. The administration of Retinol Palmitate may be a new regimen to treat AML (M3) in aged patients in poor condition.

Administration, Oral↗

Decreased cerebral glucose metabolism associated with mental deterioration in multi-infarct dementia.

Cerebral glucose metabolism of 18 patients with multi-infarct dementia (MID) and 10 age-matched normal subjects were examined with positron emission tomography and the 18-F-fluoro-deoxy-glucose technique. MID patients had significantly lower glucose metabolism in all the grey matter regions measured and were also characterized by more individuality in metabolic pattern. MID patients were also evaluated as to intelligence quotient (IQ). A positive correlation between IQ as shown by the Tanaka-Binet test and glucose metabolism for the entire grey matter was found. The clinical applicability of this test for predicting cerebral metabolism is discussed.

Aged↗

Nicotine improves cognitive disturbance in rodents fed with a choline-deficient diet.

The effect of nicotine on learning disturbances was tested in rats. Rats were fed either a choline-enriched or a choline-deficient diet. Concentration of acetylcholine in the whole brain was significantly lower in rats fed with choline-deficient diet than rats fed with choline-enriched diet. Passive avoidance learning shows that rats on a choline-deficient diet showed significantly impaired learning compared to rats on a choline-enriched diet. Nicotine (0.04 mg/kg) administered intraperitoneally significantly potentiated learning in rats on a choline-deficient diet, as well as in rats on a choline-enriched diet. We, therefore, suggest that nicotine may potentiate learning in an acetylcholine-deprived brain.

Acetylcholine↗

T cell-mediated inhibition of erythropoiesis in aplastic anaemia: the possible role of IFN-gamma and TNF-alpha.

The inhibitory activity of T cells on autologous erythroid colony-forming units (CFU-E) (T cell inhibitory activity) in patients with aplastic anaemia (AA) was investigated. In 11 (32.4%) out of 34 AA cases, T cell inhibition on autologous CFU-E growth was greater than that in normal individuals. In order to evaluate the mechanism of this inhibitory activity, T cell surface markers, interferon (IFN) production in peripheral blood mononuclear cell (PBMNC) liquid culture, and cytokine levels such as IFN and tumour necrosis factor-alpha (TNF-alpha) in CFU-E clot cocultured with T cells, were measured in a portion of the patients. In five patients investigated for IFN production in PBMNC liquid culture, all produced statistically more IFN activity than normal individuals under phytohaemagglutinin (PHA-P) stimulation (P less than 0.01) with no relation to T cell inhibitory activity. In only one patient whose T cells displayed increased CD8 and HLA-DR antigen (CD8+HLA-DR+) and inhibitory activity, a significant amount of IFN-gamma was observed in CFU-E clot cocultured with T cells, and the addition of anti-IFN-gamma antibody to the coculture resulted in recovered CFU-E colony growth. These results suggest that IFN-gamma production by T cells may explain, at least in part, the pathogenesis of haematopoietic defects in AA. In other patients however, T cell inhibitory activity neither correlated to the T cell subpopulations (CD4+/CD8+, CD8+HLA-DR+), IFN production in PBMNC liquid culture, nor to IFN and TNF-alpha levels in CFU-E clot culture. The roles played by cytokines other than IFN and TNF-alpha on haematopoietic precursor cells require further evaluation in a larger sample of patients with AA.

Adolescent↗

Studies on antidiabetic agents. X. Synthesis and biological activities of pioglitazone and related compounds.

Various analogues of a new antidiabetic agent, pioglitazone (AD-4833, U-72107), were synthesized in order to study in more detail the structure-activity relationships of this class of drug. 5-(4-Pyridylalkylthiobenzyl)-2,4-thiazolidinediones (I), thia-analogues of pioglitazone, were prepared via Meerwein arylation of the alkylthioanilines (IV). 5-(4-Pyridylalkoxybenzylidene)-2,4-thiazolidinediones (IIa) and related heterocyclic analogues (IIb) were synthesized by Knoevenagel condensation of the aldehydes (VIII) with the corresponding azolidinones. Compounds I and II were evaluated for hypoglycemic and hypolipidemic activity in genetically obese and diabetic yellow KK (KKAy) mice. Several 5-[4-[2-(2-pyridyl)ethoxy]-benzylidene]-2,4- thiazolidinediones (IIa) were equipotent to pioglitazone. However, the thia-analogues (I) and the benzylideneheterocycles (IIb) had decreased activity. Catalytic hydrogenation of the 5-benzylidene analogue (14) was found to be a convenient new synthetic method for pioglitazone. The configuration of 14 is also discussed.

Animals↗

Synthesis and biological activities of new 1,4-benzothiazine derivatives.

New 2H-1,4-benzothiazin-3(4H)-one derivatives possessing (4-phenyl-1-piperazinyl)alkyl moieties at the 2-position were synthesized and tested for calcium antagonistic and calmodulin antagonistic activities. Antihypertensive effects in spontaneously hypertensive rats were also evaluated. In general, these compounds were rather weak calcium channel blockers, although, in contrast, many of them had moderate to potent calmodulin antagonistic activity, and 2-[3-(4-(4-fluorophenyl)-1-piperazinyl]propyl]-2H-1,4-benzothiazin -3 (4H)-one derivatives 45, 74 and 75 showed potent antihypertensive effects.

Animals↗

Synthesis and biological activities of new 2-substituted 1,4-benzoxazine derivatives.

A series of new 1,4-benzoxazine derivatives (XI, XII) possessing (4-phenyl-1-piperazinyl)alkyl moieties at the 2-position and related compounds (XIII) were synthesized and tested for calcium antagonistic, calmodulin antagonistic and antihypertensive activities. Various compounds had in vitro calmodulin antagonistic activity superior or comparable to that of trifluoperazine. Among these compounds, tetrahydronaphtho[2,3-b] [1,4]oxazine derivatives such as 51, 53, 54, 58, 59, 60, 73 and 75 showed potent antihypertensive effects in spontaneously hypertensive rats. Optical isomers of 51 were also synthesized and evaluated biologically. No differences in biological activities were seen between the enantiomers.

Animals↗

Portable digital subtraction angiography in the operating room and intensive care unit.

A simple, inexpensive method of portable digital subtraction angiography (DSA) using an image processor (Sigma X), still-videorecorder and control panel combined with a surgical x-ray television unit can provide real time subtraction images on the monitor. This portable DSA unit was used in 161 cases (130 in the operating room and 31 in the intensive care unit). In the operating room it is useful: 1) to confirm patency of the parent artery and its branches after aneurysm clipping, 2) to identify feeding arteries of arteriovenous malformation and to confirm total extirpation, 3) to confirm the patency of extracranial-intracranial bypass, 4) to confirm patency of the internal carotid artery and absence of flap formation after carotid endarterectomy. In the intensive care unit, it is particularly useful for visualizing cerebral vasospasm after subarachnoid hemorrhage and recanalization of an occluded major intracranial artery. Absence of intracranial circulation can be demonstrated in patients with suspected brain death.

Angiography, Digital Subtraction↗

Measurement of D2 dopamine receptor-specific carbon-11-YM-09151-2 binding in the canine brain by PET: importance of partial volume correction.

Carbon-11-YM-09151-2 binds highly selectively to D2 dopamine receptors in the brain. Using this ligand, D2 dopamine receptor density (Bmax) and affinity (Kd) in canine striatum were measured. After administering various doses of the ligand in nine experiments, regional uptake was followed by repeated PET scanning for up to 80 min. D2 dopamine receptor specific binding at equilibrium was defined as striatal minus occipital activity after partial volume correction. Bmax and Kd were estimated by Scatchard analysis to be 40.3 pmole/ml of tissue and 22.9 nM, respectively. When a low mass dose of the ligand was administered, the bound-to-free ligand ratio in the striatum at equilibrium was consistent with the Bmax/Kd value obtained from the Scatchard analysis. The present study demonstrates the importance of partial volume correction and the Bmax/Kd measurement in a single PET study with carbon-11-YM-09151-2.

Animals↗

[Posterior interosseous nerve paralysis caused by ganglion: a case report].

A 63-year-old man presented with a posterior interosseous nerve palsy secondary to a ganglion compressing the nerve against the arcade of Frohse. Decompression and neurolysis resulted in full functional recovery. While patients with the so-called classic "Saturday night palsy" or even patients with a radial nerve palsy secondary to a fractured humerus may be expected to recover completely without surgery, early surgery is the conservative approach in patients with a nerve palsy secondary to the mass. However it is difficult to diagnose the nerve palsy secondary to the small mass. The treatment for patients with a progressive nerve palsy of unknown origin must be given attention.

Fingers↗

[A case of epidural hematoma due to dural metastasis].

A case of epidural hematoma due to dural metastasis is reported. A 62-year-old man was admitted to our hospital with generalized convulsion. A month prior, he underwent a tumor-removal operation for dural metastasis of lung cancer. CT scan on admission showed an epidural hematoma at the left frontal region. At operation, the epidural hematoma and dural invasion of neoplasm was found and removed. Pathological examination revealed dural metastasis of the poorly differentiated adenocarcinoma. According to the literature, intracranial metastasis of a bronchogenic carcinoma bleeds more often than that of other carcinomas. The particular vascular invasiveness of the neoplasm or a hemorrhagic diathesis is considered as the cause of the hemorrhage. In the present case the pathogenesis of the hemorrhage was thought to be the hypervascularity of the rapid growth tumor, fragility of the tumor vessels, and invasiveness of the tumor into the dural vessels. Adding to these, two other factors could play an important role in forming epidural hematoma; 1) the tumor existed mainly in the epidural surface and 2) dural adhesion of the cranial bone was not so tight.

Adenocarcinoma↗

Cerebral circulation and oxygen metabolism associated with subclinical periventricular hyperintensity as shown by magnetic resonance imaging.

A combined magnetic resonance imaging and positron emission tomography study was performed on 21 patients with cerebrovascular risk factors but without neurological abnormalities. Our purpose was to investigate the hypothesis that periventricular hyperintensity (PVH) reflects ischemia. Periventricular hyperintensity was evaluated with a method we devised, and cerebral circulation and oxygen metabolism were evaluated with the oxygen-15 steady-state technique. We concluded that the brain with severe periventricular hyperintensity had abnormal circulation, although oxygen metabolism was not measurably affected. The role of a compensation mechanism under conditions of decreased oxygen supply was considered.

Aged↗