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Biomedical subjects

I Nakamura

Publications and source records attributed to I Nakamura.

At least 19 recordsLinked to original sources

Hemopoietic histocompatibility (Hh-1) phenotype and the regulation of its expression.

Hybrid resistance (HR) is primarily controlled by the genes of the Hemopoietic histocompatibility-1 (Hh-1) locus within the H-2 complex. HR is a consequence of the Hh-1-controlled target determinants in homozygous parental strain mice and their absence in heterozygous F1 hybrid mice. To examine the mechanism that controls the Hh-1 phenotype, three independent clones of somatic cell hybrids between parental lines EL-4 (C57BL/6 origin, H-2b) and R1 (C58 origin, H-2k) were studied. The line EL-4 is Hh-1b-positive and is subject to HR by H-2b heterozygous F1 mice, but R1 lacks the Hh-1b allele and is not susceptible to HR. Of the three hybrid clones, F263.2 is Hh-1b-positive, whereas the other two, F262.2 and F264.2, are Hh-1b-negative, as judged by these cells' capacity to compete in vivo with the grafted parental C57BL/6 bone marrow cells in the resistant (C57BL/6 x C3H)F1 mice. All three clones express the H-2b and H-2k class I antigens equally well, are susceptible to activated NK cells to the same extent, and all carry four copies of chromosome 17. However, Southern analysis reveals that clone F263.2 contains three copies of H-2b chromosome and one H-2k, whereas the other two clones carry two copies each of the parental chromosome 17. The results suggest that the relative copy number of specific alleles is the crucial determinant of the Hh-1 phenotype, and render unlikely both the gene dosage hypothesis and the trans-acting dominant suppression hypothesis to account for the noncodominant expression of the Hh-1 phenotype.

Animals

Pathology of the cerebellar dentate and interpositus nuclei in Joseph disease: a morphometric investigation.

Cerebellar dentate and interpositus nuclei pathology was studied morphometrically in 3 patients with Joseph disease compared to 3 control subjects. Size of neurons, number of small neurons (cell body area: 50-199 microns 2) and large neurons (cell body area: 200 microns 2 or greater) at the rostral, medial and caudal levels, neuronal cell density, total volume of the gray bands, and total neuronal cell number were evaluated in the dentate, emboliform, and globose nuclei, using an image analyzer, after making horizontal serial 20-microns thick sections of a unilateral cerebellar hemisphere embedded in celloidin. The number of large neurons in Joseph disease was around 20% of that in the controls at each level in the individual nucleus (P less than 0.05 or P less than 0.01). In contrast, the number of small neurons was significantly reduced only at the caudal level of the dentate nucleus (P less than 0.05). The neuronal cell density was decreased within the nuclei. The total volume of the gray bands was reduced to about 70% within the nuclei (P less than 0.05 or P less than 0.01). The total number of neurons was decreased to about a third, a half, and a third within the dentate (P less than 0.001), emboliform (P less than 0.01), and globose nuclei (P less than 0.001), respectively. The principal pathologic change of the dentate and interpositus nuclei in Joseph disease was severe loss of neurons, with significant loss of the large neurons, indicating that Joseph disease is a type of cerebellar efferent system disorder.

Adult

Identification of a binding protein to the X gene promoter region of hepatitis B virus.

The X protein of hepatitis B virus (HBV) is a transactivator to homologous and heterologous viral and cellular transcriptional regulatory elements. One sequence-specific binding protein, whose binding site located from nt 1102 to nt 1117 of HBV DNA, was identified by mobility shift assay and DNase I foot-printing analysis. A CAT assay experiment demonstrated this 16-bp binding site to have a promoter activity in the X gene transcription. The 58-bp DNA fragment (nt 1085 to nt 1142), which contains the above binding site, could be enhanced by the HBV enhancer. Mobility shift assay using the mutated 58-bp DNA fragments as probes, showed that the mutation, which damaged the palindrome structure between nt 1105 and nt 1112, resulted in loss of the binding activity. This mutation also remarkably reduced the promoter activity. The binding site differed from the target sequences of known transcriptional factors. This factor was thus concluded to be a binding protein to the X gene promoter (X-PBP) of HBV. A homology search demonstrated the binding site to be highly homologous to the promoter elements of human laminin receptor (2H5epitope) and lipoprotein receptor-related protein (LRP) genes.

Base Sequence

The alterations of norepinephrine and acetylcholine concentrations in immature rat urinary bladder caused by streptozotocin-induced diabetes.

The concentrations of norepinephrine (NE) and acetylcholine (ACh) in the body and base of the bladder were investigated two, four and eight weeks after the administration of streptozotocin to four-week-old rats. At four and eight weeks after following dosage, NE concentrations in the base of the bladder of the diabetic rats were significantly higher than those of control rats. At the two-week diabetic condition, ACh concentrations in both the body and base of the bladder diabetic rats were about two-fold higher than in the respective control levels and remained constant for eight weeks. However, the control rats showed dramatic increase in ACh concentration from two to four weeks after dosage. There was no significant difference in the response of bladder muscle strips to phenylephrine, isoproterenol and ACh in the diabetic vs. control rats throughout the experiment. These observations suggest that the alteration of autonomic nervous system may occur at an early stage of diabetes mellitus in immature rats and that the high concentration of NE in the diabetic bladder base may reflect an adaptive overfunction of the adrenergic system probably to maintain continence. Furthermore, the lack of change in ACh concentration with age in diabetic rats may suggest an impaired development of the cholinergic system.

Acetylcholine

The role of the seminal vesicles and coagulating glands in fertilization in the rat.

To investigate the role of the seminal vesicles (SV) and coagulating glands (CG) in fertilization in the rat, partial resections of the SV (25%--group B), 50%--group C, and 75%--group D) or bilateral resection of the SV alone (100%--group E), or together with the CG (group F) were undertaken. In other groups, bilateral resection of the CG only (group G), or bilateral resection of the CG with ipsilateral SV resection (group H) were performed. A group of sham-operated rats served as controls (group A). There were no significant differences among groups A, B, C and D in the number of fertile rats post-operatively but significant differences were evident in groups E, F, G, H when compared with the control group (P less than 0.01 for all groups). Only the fertile rats were able to form copulatory plugs (CP) post-operatively. Bilateral ligation of the SV ducts was performed in ten fertile rats. Post-operatively, the proportion of fertile rats was decreased significantly (P less than 0.01). Removal of the ligatures resulted in a significant increase (P less than 0.01) in fertility. It was also demonstrated that the addition of rat seminal vesicular secretions (SVS) to epididymal sperm suspensions resulted in a significant decrease (P less than 0.001) in sperm motility. These results suggest that the SV and CG are necessary for fertility in rats, and that one role of SVS is the formation of a CP and not the maintenance of sperm motility.

Animals

Cytoskeletal protein abnormalities in patients with olivopontocerebellar atrophy--an immunocytochemical and Gallyas silver impregnation study.

A highly sensitive silver technique for glial cytoplasmic inclusions (GCI) in olivopontocerebellar atrophy (OPCA) was applied to tissues from 15 patients with neurodegenerative disorders including OPCA, Joseph disease, Alzheimer's disease (AD), Huntington's chorea, Pick disease and three control non-neurological subjects. Brain tissue from both OPCA and AD impregnated positively. Neurons, astroglia and oligodendroglia in the putamen, pontine nucleus and inferior olivary nucleus all impregnated in addition to white matter oligodendroglia. Neuronal inclusions in the pontine nucleus appeared as compact or fibrillary masses, and GCI-bearing oligodendroglia and astrocytes showed homogeneously impregnated somata. The myelinated pontocerebellar tract and the white matter surrounding the inferior olivary nucleus contained a small number of impregnated nerve fibres with a hollow structure, which resembled the myelin sheath. Immunocytochemical studies to clarify these argyrophilic structures in the OPCA subjects employed paired helical filament (PHF), microtubule associated proteins (MAPs), MAP1, MAP2, MAP5, tau, ubiquitin, neurofilament (200 or 70 kilodaltons) and myelin basic protein (MBP) antisera. GCI-bearing white matter oligodendroglia expressed PHF, tau, MAP5 and ubiquitin immunoreactives and non-argyrophilic astroglia were positive for MAP5 antiserum alone. In the putamen, pontine nuclei and inferior olivary nuclei, impregnated neurons as well as the GCI-bearing oligodendroglia immunostained with PHF, tau, MAP5 and ubiquitin antisera and impregnated astroglia were also immunoreactive to these antisera except for being tau negative in the putamen. Silver impregnated nerve fibres showed only MBP immunoreactivity. These findings indicate that the argyrophilia in the OPCA subjects closely correlates with PHF and tau immunoreactivities.

Aged

Solubilization and promoter analysis of RNA polymerase from rice stripe virus.

The RNA-dependent RNA polymerase associated with rice stripe virus was dissociated from viral RNA (vRNA) by CsCl centrifugation. The solubilized RNA-free RNA polymerase transcribed a model RNA template 50 nucleotides in length carrying the 5'- and 3'-terminal conserved sequences of all four genome RNA segments. A 3'-terminal half molecule of the model template was also active as a template. Hence, we propose that the 3'-terminal conserved sequence serves as a promoter for the rice stripe virus-associated RNA polymerase. The solubilized enzyme, however, was unable to transcribe vRNA. The failure of the solubilized enzyme to transcribe vRNA is discussed in relation to the apparent loss of RNA polymerase activity after treatment of virions with high concentrations of salt.

Base Sequence

Are there sequential morphometrical changes in the nucleus basalis in Alzheimer's disease?

Degenerated neurons of the nucleus basalis of Meynert (nbM) were quantitatively analyzed in 3 normal and 3 Alzheimer's disease (AD) subjects. In this study, the Ch4 of the nbM was examined using the indirect immunoperoxidase method with a monoclonal antibody to acetylcholinesterase (AChE) counterstained with cresyl violet. AChE-rich neurons were designated as the cholinergic neurons. The cross-sectional area of all the Ch4 neurons with clearly visible nucleoli in one preparation was measured using a computer image analyzing system. Furthermore, we compared these data with the numbers of neurofibrillary tangles (NFTs) and neuritic plaques (NPs) in the temporal cortex by Gallyas silver stain. The cholinergic neurons decreased in number and size according to the length of the disease duration but the surviving cholinergic neurons in the size range from 800 to 1,000 micron 2 in a case with short clinical duration were increased in number. The non-cholinergic neurons showed only atrophy without definite neuronal cell depletion. The 400- to 1,000-microns 2-sized non-cholinergic neurons were markedly decreased in number, and the number of 300-microns 2-sized non-cholinergic neurons remained unchanged. Although there was an inverse correlation between the degree of atrophy and depletion of the cholinergic neurons with the number of NFTs and NPs in 2 AD cases with 3 and 6 years of disease duration, this correlation was not found in an AD case with 12 years of disease duration, probably due to extensive and profound grey matter degeneration.

Acetylcholinesterase

Surgical repair versus medical treatment of varicocele in the rat: pharmacological manipulation of the varicocelized testicle.

Human chorionic gonadotropin, kallikrein, indomethacin, and hydralazine were administered to different groups of varicocelized rats, while surgical repair of the varicocele was performed in another group of rats. The effects of conservative and surgical treatment on epididymal sperm content and motility, the weights of the testes, epididymis, and male accessory genital glands, and fertility were compared between each group and a sham-treated group of rats. Surgical repair significantly improved all the evaluated parameters and all the conservative regimens, except hydralazine, resulted in a significant improvement in most parameters. Our results indicate that stimulation of the Leydig or/and Sertoli cells of a varicocelized testicle can counteract some of the detrimental consequences of the varicocele itself.

Animals

[A study of the humoral immunity of mice injected with beryllium chloride].

We studied changes of humoral immunity, such as complement pathway activity, C3 contents and contents of immunoglobulin, in mice injected subcutaneously with BeCl2 or CuCl2 once a week for 12 weeks. Mean body weights of JCL: ICR female mice were approximately 30g in control mice (control group; n = 7), in mice injected with Be (Be group; n = 8) and in mice injected with Cu (Cu group; n = 8). Values of classical complement pathway activity (CH50) were 18.8 +/- 1.4 U per ml, 15.3 +/- 1.8 U per ml and 16.7 +/- 1.3 U per ml in the control group, Be group and Cu group, respectively. The CH50 values of Be and Cu groups were significantly lower than that of the control group (P < 0.01). In contrast, values of alternative complement pathway activity (ACH50) and contents of C3 were almost constant in the three groups. The immunoglobulin content in the Be group tended to increase. The activity of alanine aminotransferase in the Be group was markedly higher than that in the control group (P < 0.05), and the aspartate aminotransferase activity was also high. The CH50 value of mice injected with a small amount of Be once a week over a 12-week period decreased markedly, although either the ACH50 value or C3 content was the same as in the control group. The immunoglobulin content somewhat increased in the Be group. These results suggest the possibility that immune complex is induced by Be.

Animals

[Determination of protoporphyrins in blood using HPLC. Standardization of protoporphyrins and interlaboratory comparison of analyses].

1) In order to compare the results of determination of protoporphyrin IX (PP) and zinc protoporphyrin IX (ZP) using HPLC, the preparation procedures for standard solutions of PP and ZP were studied at four laboratories. According to the methods mutually agreeable to the four laboratories, the absorption values using UV-Vis spectrometer from the 4 laboratories were found to be identical. 2) The total of 28 whole blood samples obtained from the same workers whose Pb-B levels ranged from 2.9 to 87.9 micrograms/dl were sent to the 4 laboratories for determination of PP and ZP. The laboratories were allowed to use their own HPLC apparatus, column, mobile phase and fluorometric detectors, although the same procedures were used to prepare the standard solutions of PP and ZP. The results showed that significant biases in ZP and PP levels were found between two out of the 4 laboratories, but the ZP values corrected by the recovery rate showed no statistical difference among the laboratories. 3) Blood levels of ZP, total protoporphyrin (TP, calculated by PP+ZP/1.1), and PP determined by HPLC method correlated well with free erythrocyte protoporphyrin (FEP) determined by the method of extraction into the acidic solvent. The correlation coefficients between Pb-B and log TP, ZP, FEP or PP were 0.82-0.84, 0.80-0.83, 0.786, or 0.70-0.73, respectively. 4) The coincident ratios of PP/TP obtained at 4 laboratories ranged from 12.1 to 19.0%. These values were within a relatively narrow range, although two different kinds of organic solvents (DMF: N',N'-dimethylformamide or Methanol/triton-X 100) were used in the extraction steps.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid

Gallyas-Schiff stain for senile plaques.

Gallyas technique was modified by a direct application of Schiff's reagent after physical development, resulting in distinctive staining of amyloid deposits in argyrophilic structures. With this modified method, senile plaques in Alzheimer's disease are clearer. This method is easy to perform and suitable for routine neuropathological examination.

Alzheimer Disease

[Kock-rectal bladder. Augmented and valved rectum].

Eight patients with total cysto-urethrectomy underwent an augmented and valved rectum (Kock), a type of continent urinary diversion. A satisfactory outcome was obtained in 6 patients. These 6 patients urinated 6 to 8 times a day (1-2 times during the night). The volume each time was 350-450 ml. Urinary incontinence occurred only 1-2 times a month when deeply asleep, and there were no patients whose daily life was restricted. However, there were 3 patients with urinary tract complications. In 2 of them, urinary diversion was required, and unilateral total ureteral obstruction was observed in the remaining patient. The reason for the complications appeared to be that stapling of the intussusception of the sigmoid colon was performed in 5 placements as described in the original method. Following the 4th patient, we were able to prevent any complication in the urinary tract by stapling of the intussusception in 3 places (at 12, 5 and 7 o'clock), and by suturing mucosa to mucosa of the rectum and intussusception in 6 places with polyglycolic acid suture, and further suturing serosa to serosa of the sigmoid colon and rectum in 4 places with silk suture.

Aged

An autopsy case of tuberous sclerosis. Histological and immunohistochemical study.

We report an autopsy case of tuberous sclerosis. A 19-year-old Japanese man had shown facial adenoma sebaceum, intractable convulsive seizures and severe mental retardation. Gross inspection of the brain showed a cortical tuber from the orbital frontal lobe to the rhinencephalon of the left side and a few subependymal nodules. Histological examination revealed many cortical tubers in the cerebral hemispheres, a few subependymal nodules with calcification and multifocal clusters of heterotopic cells in the white matter (white matter nodules). In these lesions, massive giant cells with abundant eosinophilic cytoplasm and without Nissl substances were found. Although the size and shape of the giant cells were variable, the majority of them were gemistcytic, ovoid or polygonal. Immunohistochemistry was employed in these lesions using antibodies against neurofilament protein (NFP), glial fibrillary acidic protein (GFAP), vimentin (VM) and myelin basic protein (MBP). In the cortical tuber, the majority of the giant cells were positive for both NFP and VM, but a few were positive for GFAP. All of them were negative for MBP. In the subependymal nodule and white matter nodule, the majority of the giant cells were positive for NFP, but a few were positive for VM, and none were positive for either GFAP and MBP. These findings suggest that the majority of the giant cells may be immature cells toward neuronal series and a few may be those toward astroglial series. These findings also indicate that the giant cells in the subependymal nodule and white matter nodule may be more differentiated than those in the cortical tuber. The nature of the giant cells in tuberous sclerosis is discussed.

Adult

[Acute pulmonary edema in five patients undergoing sevoflurane anesthesia].

Four adults and a child undergoing surgery with sevoflurane anesthesia developed acute pulmonary edema immediately after anesthesia. Prior to development of pulmonary edema all patients exhibited severe arterial hypertension and tachycardia. Their episodes of circulatory changes were, we believed, caused by the local injection of epinephrine for hemostasis in 2 patients (9 y.o. child, 45 y.o. man) and the intrusion of painful surgical stimuli in one patient (67 y.o. man). Circulatory changes in these three patients were treated by increasing the inspired sevoflurane concentration. We, however, speculate that the increase in inspired sevoflurane decreased the cardiac output and that the resulting increase in pulmonary wedge and capillary pressures was caused by an abrupt increase of arterial blood pressure, followed by a rapid increase in afterload due to cardiac suppression from the high concentration of sevoflurane. In 2 patients (74 y.o. man, 61 y.o. woman) arterial hypertension occurred during endotracheal extubation after sevoflurane anesthesia. Because of fast uptake and elimination of sevoflurane due to a low blood/gas partition coefficient, a fast awakening in the latter 2 patients, may be responsible for the abrupt increase in arterial blood pressure. In conclusion, it should be noted that pulmonary edema may be involved when severe circulatory changes occur in a patient undergoing sevoflurane anesthesia.

Acute Disease

[Cytoskeletal proteins abnormalities in olivopontocerebellar atrophy].

A highly sensitive silver technique for glial cytoplasmic inclusions in olivopontocerebellar atrophy (OPCA) was applied to 15 subjects with neurodegenerative disorders including 4 patients with OPCA, 4 patients with Joseph disease and with 3 normal control subjects, and the argyrophilic structures in the OPCA cases were immunocytochemically examined. As a result, the argyrophilic structures were found in the OPCA cases and Alzheimer cases. The argyrophilic structures included the white matter oligodendroglia, and neurons, astroglia and oligodendroglia in the putamen, pontine nucleus and inferior olivary nucleus. The pontocerebellar tracts and the surrounding white matter of the inferior olivary nucleus contained a small number of argyrophilic nerve fibers with a hollow structure, which were interpreted as myelin. Immunocytochemistry demonstrated that the oligodendroglia in the white matter had immunoreactivities to an paired helical filament (PHF), microtubule associated protein 5 (MAP5), tau and ubiquitin antiserum, and the astroglia in the white matters had an immunoreactivity to a MAP5 antiserum. In the putamen, pontine nucleus and inferior olivary nucleus, in addition to the immunoreactivities observed in the oligodendroglia, the neurons were immunoreactive for PHF, MAP5, tau and ubiquitin antisera, and the astroglia had the same immunoreactivities as the neurons except for being tau negative in the putamen. The nerve fibers in the pontocerebellar tract and inferior olivary nucleus capsule were strongly positive for myelin basic protein and negative for PHF antiserum. These findings indicate that the Gallyas positive argyrophilia in the OPCA subjects is closely associated with PHF or tau.

Aged

Effects of long-term medication for essential hypertension on cardiac hypertrophy and function.

The effects of long-term treatment of hypertensive patients with alacepril (angiotensin-converting enzyme inhibitor) on cardiac mass and function were investigated. A total of 12 patients was examined. Both systolic and diastolic blood pressure were significantly reduced by treatment with alacepril for 1 year. Left ventricular mass, as estimated by echocardiography, was significantly decreased by alacepril treatment, although electrocardiographic and chest x-ray findings were not significantly altered. Cardiac pump function, which was also assessed by echocardiography, was not changed. These results indicate that long-term treatment of hypertension with alacepril induces regression of cardiac hypertrophy without any change in cardiac contractile function.

Adult

Membranous lipodystrophy (Nasu-Hakola disease) with thalamic degeneration: report of an autopsied case.

An autopsied case of membranous lipodystrophy (Nasu-Hakola disease, NHD) with thalamic degeneration was reported. A 34-year-old Japanese man was diagnosed as having NHD by bone biopsy prior to the onset of clinical symptoms. His maternal grandfather and paternal grandmother are cousins, but this family history is negative for NHD. He developed frontal lobe syndrome at the age of 35 with progressive dementia, and died of acute renal failure at the age of 46. Gross inspection of the brain detected atrophy and softening of the cerebral white matter, predominantly in the frontal lobe. Microscopically, numerous spheroids, predominant fibrillary gliosis with less prominent demyelination "dissociation glio-myélinique" and scanty sudanophilic lipid droplets were observed, indicating the sclerosing type of NHD. An unusual patholgoical finding in this case was selective involvement of the thalamic nuclei with preservation of the other gray matter except for focal cortical necrosis. The topography of the affected thalamic nuclei is similar to that of systemic thalamus degeneration. An association with thalamic degeneration in NHD has not been previously reported. The present case suggests that NHD also affects the thalamus.

Adult