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Biomedical subjects

H Nogami

Publications and source records attributed to H Nogami.

At least 19 recordsLinked to original sources

[Prognosis of intractable asthma].

Forty-nine intractable asthma patients from January 1981 were divided into three groups. Group I consisted of patients still alive after ten years (January 1991) who were receiving decreased doses of steroids or no steroids at all. Group II patients were also alive, but the doses of steroids they were receiving were unchanged. Group III consisted of patients who had died during the ten years. Of the 49 patients, nine were in Group I, 13 in Group II and 17 in Group III. The condition of the other 10 patients was unknown. The mortality rate of the known 39 patients over 10 years was 43.6%, a very high rate. The groups of living patients (I + II) were younger than the patients in the dead group (III) and the latter patients had more obstructive ventilatory dysfunction in the stable state (FEV1.0/FVC%, and %FEV1.0 were 56.1% and 52.8%) in 1980. In the therapy carried out over the 10 years, antiallergic drugs and inhaled steroids were administered in order to decrease oral steroids in both Group I, II and III. In Group I, however, more patients had received immunotherapy (hyposensitization) or gold therapy than in Group II and III. There were more complications due to steroids during the ten years in Group II and III than in Group I. Aging and obstructive ventilatory dysfunction may be factors which worsen the prognosis of intractable asthma, and decreasing of the doses of oral steroids may be important to prevent complications.

Adolescent

Coffin-Lowry syndrome associated with calcium pyrophosphate crystal deposition in the ligamenta flava.

Clinical and ultrastructural study of four cases of Coffin-Lowry syndrome (CLS), a heritable disorder with peculiar facies, stooped posture, vertebral changes, and mental retardation, is reported. Three of the four cases had myelopathy caused by calcification of the ligamenta flava in early adulthood. These patients demonstrated that CLS is a calcium pyrophosphate dihydrate crystal deposition disease, and it is postulated that a metabolic abnormality in collagen and in proteoglycans are responsible for some aspects of CLS.

Adolescent

Immunohistochemistry of the pituitary pars distalis of the musk shrew, Suncus murinus.

Immunocharacteristics of the pituitary pars distalis cell types of the musk shrew, Suncus murinus, were studied by the unlabeled antibody enzyme technique, using peroxidase-antiperoxidase or avidin-biotin-peroxidase complex. The thyrotropin (TSH)-, gonadotropin (GTH)-, corticotropin (ACTH)-, prolactin (PRL)-, and growth hormone (GH)-secreting cells of the PD were identified on the basis of their immunoreactivity with different heterologous antisera. The TSH cells showed specific immunoreactivity with antisera against human (h) TSH beta and rat (r) TSH beta. Cells showing immunoreactivity with the antisera against hLH beta and ovine (o) LH beta were designated as GTH cells as no immunoreactivity was observed with antisera against hFSH beta and oFSH beta. The ACTH cells as well as the cells of the pars intermedia were revealed by anti-ACTH1-24 and anti-ACTH1-10 sera. Whereas the PRL cells were recognized by their immunoreactivity with antisera against hPRL and oPRL, the GH cells were identified with anti-hGH, anti-oGH, and anti-bovine (b) GH sera. TSH and GTH, TSH and ACTH, GTH and ACTH, ACTH and GH, ACTH and PRL, and GH and PRL cells were visualized in the same section using the dual immunoperoxidase technique. Comparison of the immunohistochemically identified cells with those described histochemically reveals several discrepancies, which expose the limitations of the latter techniques identifying adenohypophysial cells.

Adrenocorticotropic Hormone

Zonal and age-related difference in the amounts of creatine kinase subunits in cartilage.

Energy metabolism in cartilage may affect the morphogenetic events of skeletal growth. Investigating enzymes responsible for energy metabolism in cartilage, such as creatine kinase (CK), can provide clues to an understanding of pathogenesis and treatment of osteochondrodysplasias. In this study levels of CK subunits M (muscle type) and B (brain type) were measured by a highly sensitive enzyme immunoassay system in growth and resting cartilages of the rat rib at various ages. CK-M was predominant, but there was no statistically significant difference in its quantity of CK among cartilages of various ages or between resting and growth cartilage. In contrast, although CK-B levels were low, they showed a significant decrease with advancing age and a significant increase in growth cartilage as compared with resting cartilage. The results of this study suggest that CK in cartilage, especially CK-B, may play an important role in skeletal growth.

Aging

Allelic association of human dopamine D2 receptor gene in alcoholism.

In a blinded experiment, we report the first allelic association of the dopamine D2 receptor gene in alcoholism. From 70 brain samples of alcoholics and nonalcoholics, DNA was digested with restriction endonucleases and probed with a clone that contained the entire 3' coding exon, the polyadenylation signal, and approximately 16.4 kilobases of noncoding 3' sequence of the human dopamine D2 receptor gene (lambda hD2G1). In the present samples, the presence of A1 allele of the dopamine D2 receptor gene correctly classified 77% of alcoholics, and its absence classified 72% of nonalcoholics. The polymorphic pattern of this receptor gene suggests that a gene that confers susceptibility to at least one form of alcoholism is located on the q22-q23 region of chromosome 11.

Alcoholism

Molecular mechanism of growth hormone (GH) deficiency in the spontaneous dwarf rat: detection of abnormal splicing of GH messenger ribonucleic acid by the polymerase chain reaction.

The spontaneous dwarf rat (SDR) is an experimental model for pituitary dwarfism with an autosomal recessive mode of inheritance. In the pituitary of the SDR, neither GH cells nor GH protein were detected by immunological methods, but SDR pituitary has a very small amount of GH mRNA. In the present study the effects of GH-releasing factor and an analog of its second messenger, (Bu)2cAMP, on the total accumulation and secretion of GH were studied in primary cultures from SDR pituitaries. GH-releasing factor and (Bu)2cAMP increased the amount of GH mRNA, but neither accumulation nor secretion of immunoreactive GH was detected. These results suggested that the mutation is not manifest during transcription, but at a later stage. The GH gene of SDR was cloned, and its sequence was determined. A point substitution was found in the consensus sequence of the 3' splice site of the third intron. Judging from this point mutation, one would predict an abnormal splicing and a 1-base deletion in the GH mRNA. Therefore, the fragment of SDR GH cDNA in which the deletion was predicted was amplified by the polymerase chain reaction. Its sequence analysis confirmed that the SDR GH mRNA had 1 base deletion which must cause a premature translational termination of GH mRNA. These results demonstrate that GH deficiency in SDR is caused by a point mutation in the GH gene producing an abnormal splicing of GH mRNA.

Animals

Bioassay of chondrocyte differentiation by bone morphogenetic protein.

For sensitive bioassay of cartilage development in response to bone morphogenetic protein (BMP), the supernatant of interstitial fluid containing crud BMP was obtained from an implanted diffusion chamber, applied to a cellulose acetate film, and stained with Alcian blue. The optical density of the Alcian blue-stained spot was measured by a densitometer for quantitative analysis. Density of the Alcian blue-stained spot was markedly increased when cartilage developed outside the chamber. Occurrence of cartilage-specific proteoglycan-H (PG-H) and Type II collagen was seen in this intensely stained spot by dot-blot analysis. Electron microscopic examination revealed that the residue of interstitial fluid in the implanted diffusion chamber contained many collagen fibrils and proteoglycan granules.

Animals

Three distinct molecular species of proteoglycan synthesized by the rat limb bud at the prechondrogenic stage.

To characterize proteoglycans in the prechondrogenic limb bud, proteoglycans were extracted with 4 M guanidine HCl containing a detergent and protease inhibitors from Day 13 fetal rat limb buds which had been labeled with [35S]sulfate for 3 h in vitro. About 90% of 35S-labeled proteoglycans was solubilized under the conditions used. The proteoglycan preparation was separated by DEAE-Sephacel column chromatography into three peaks; peak I eluted at 0.45 M NaCl concentration, peak II at 0.52 M, and peak III at 1.4 M. Peaks I and III were identified as proteoglycans bearing heparan sulfate side chains. The heparan sulfate proteoglycan in peak III was larger in hydrodynamic size than the proteoglycan in peak I. The heparan sulfate side chains of peak III proteoglycan were smaller in the size and more abundant in N-sulfated glucosamine than those of peak I proteoglycan. Peak II contained a chondroitin sulfate proteoglycan with a core protein of a doublet of Mr 550,000 and 500,000. The chondroitin sulfate proteoglycan was easily solubilized with a physiological salt solution and the heparan sulfate proteoglycan in peak I was partially solubilized with the physiological salt solution. The remainder of the proteoglycan in peak I and the heparan sulfate proteoglycan in peak III could be solubilized effectively only with a solution containing a detergent, such as nonanoyl-N-methylglucamide. This observation indicates the difference in the localization among these three proteoglycans in the developing rat limb bud.

Amino Acids

Electron-microscopic study on the anterior pituitary gland of spontaneous dwarf rats.

The spontaneous dwarf rat is a novel experimental model animal on the study of pituitary dwarfism. The fine structure of the anterior pituitary cells was studied in the immature and mature dwarf rats. Pituitary glands were removed from 5-, 10-, 20-day-old immature dwarfs, adult (45 days-16 weeks) dwarfs and normal 3-month-old rats and processed for electron-microscopic observation. In the control animals, growth hormone cells were readily identified by their ultrastructural characteristics, such as the presence of numerous electron-dense secretory granules, 300-350 nm in diameter, well developed rough endoplasmic reticulum and a prominent Golgi complex. In contrast, growth hormone cells were not found in the anterior pituitary gland of the spontaneous dwarf rat at any age examined. Other pituitary cell types, i.e., luteinizing hormone/follicle stimulating hormone, thyroid stimulating hormone, adrenocorticotropic hormone and prolactin cells, appeared similar in their fine structure to those found in the control rats. In the pituitary gland of dwarf rats, a number of polygonal cells were observed either with no or relatively few secretory granules. The rough endoplasmic reticulum was arranged in parallel cisternae and the Golgi complex was generally prominent in these cells. In addition, many were found to have abundant lysosomes. A few minute secretory granules were occasionally observed; however, the immunogold technique failed to localize growth hormone or prolactin in the granules. The nature of these cells remained obscure in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Studies on the development of growth hormone and prolactin cells in the rat pituitary gland by in situ hybridization.

Cytogenesis of growth hormone and prolactin cells in the rat pituitary gland was studied using in situ cDNA-mRNA hybridization and immunocytochemistry. Frozen or Paraplast sections of fetal and neonatal pituitaries were hybridized with 3H-cDNAs for rat prolactin or growth hormone, and were then processed for autoradiography. A number of growth hormone mRNA-positive cells were encountered throughout the anterior lobe on day 19 of gestation. Individual variation in growth hormone gene expression was observed between fetuses at day 19 of gestation (6 out of 8 fetuses examined were positive for growth hormone mRNA). In contrast, growth hormone mRNA was detected in the all fetuses examined on day 20 or later. The autoradiographic signal (number of reduced silver grains) appeared to increase with later stages of development. Fetal growth hormone mRNA-positive cells were evenly scattered throughout the anterior lobe. Most of them were isolated, however, small clusters of several growth hormone cells were infrequently observed. Prolactin mRNA-positive cells were found first on the 22nd day (the last day of gestation) in 3 of 6 fetuses examined, but were rarely observed on earlier gestational days. By postnatal day 8, prolactin mRNA-positive cells were numerous and the grain density over prolactin cells increased. Both growth hormone and prolactin cells were found as early as 18 days of gestation using immunocytochemistry, although the number of positive cells was very small at this stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Elevated accumulation of hyaluronate in the tubular bones of osteogenesis imperfecta.

The content and composition of glycosaminoglycans in the tubular bones of osteogenesis imperfecta were compared to those in the tubular bones of age-matched controls. Chondroitin sulfate was the major glycosaminoglycan (70-80% of total) both in the normal and pathological bones, and its level, based on the tissue wet weight, was slightly less in the pathological bones. The composition of chondroitin sulfate disaccharide units in the pathological samples was different from those of the control; a lower proportion of chondroitin 4-sulfate unit. Hyaluronate accounted for at most 7% of total glycosaminoglycans from the normal bones. The hyaluronate content of the pathological bones was 1.5- to 3-fold higher than that of the controls. Glycosaminoglycans have been shown to participate in the formation of a functional supramolecular complex in extracellular matrices. Therefore, it may be postulated that the abnormalities in glycosaminoglycan composition in the tubular bones of osteogenesis imperfecta is implicated in some clinical aspects of this connective tissue disorder such as the bony fragility.

Bone and Bones

Studies on prolactin and growth hormone gene expression in the pituitary gland of spontaneous dwarf rats.

The spontaneous dwarf rat (SDR) is a newly established experimental model for pituitary dwarfism with an autosomal recessive mode of inheritance. GH and PRL gene expressions were studied in the pituitary gland of this animal. Immunocytochemistry failed to detect any immunoreactive GH cells in SDR pituitary gland, whereas numerous PRL cells were encountered throughout the anterior lobe. Similarly, GH was not detectable in the pituitary cytosol from SDR of 7, 20, and 80 days of age. PRL of the same mol wt as the authentic rat PRL was found in the pituitary glands in all SDRs examined. Since these results were thought to be due to the absence of GH mRNA in the SDR's pituitary gland, we attempted to detect GH mRNA by dot hybridization. Very small amounts of GH mRNA were found in the pituitary glands of both male (2.6% of normal) and female (6.0% of normal) SDRs. Reduced levels of PRL mRNA were also found in the pituitary glands of male (50%) and female (30%) SDRs. Northern blot analyses of total RNA extracts revealed that the GH mRNA of the SDR was similar in size to the mature GH mRNA found in the pituitary glands of control rats. PRL mRNA from the SDR also migrated to the same position as normal PRL mRNA. Nuclear DNA preparations were prepared from normal and SDR livers, and the genomic organizations of the GH and PRL genes were examined using restriction mapping. The DNA fragment length patterns obtained with the cDNA probes for GH or PRL using several restriction enzyme digestions were identical. The results suggest that the GH deficiency in SDR is not due to a gross deletion or rearrangement of the GH gene. It is proposed that SDR may be an excellent experimental model for the study of isolated GH deficiency in the human.

Animals

New assessment of airway responsiveness. Effect of pretreatment with procaterol on allergen-induced bronchoconstriction.

We examined airway responsiveness to allergen inhalation using a novel technique by which dynamic compliance (Cdyn) and pulmonary resistance (Rl) are simultaneously calculated by Fourier-series analysis of flow and transpulmonary pressure during tidal breathing. C0 and C0.5 (Cdyn at the frequency of zero and 0.5 Hz, respectively) were computed using the regression line of Cdyn versus frequency measured at the fundamental and first three harmonics in each breathing cycle. First, the validity of this system was tested by comparing Rl, C0 and C0.5 during five consecutive breaths with those obtained by the conventional method. A good correlation was seen in Rl, C0 and C0.5 between the two methods. Second, we studied airway response to allergen inhalation before and after oral administration of a long-acting beta 2-stimulant (procaterol, 50 micrograms or 100 micrograms) or placebo in a double-blind crossover trial in six atopic asthmatic subjects. In control allergen inhalation tests by administration of placebo, Rl increased progressively, and C0.5, expressed as percentage of control compliance at zero frequency (C0.5/COcont), decreased progressively. After 100 micrograms procaterol, Rl response to allergen was almost completely inhibited. However, a decrease in C0.5/C0cont was still observed. These findings suggest that pretreatment of asthmatic patients with procaterol can release allergen-induced bronchoconstriction of the central airways, but cannot release that of the peripheral airways.

Adult

Possible site of bronchodilation due to inhaled procaterol aerosol in asthmatic patients.

We studied the effective site of an inhaled aerosol of procaterol, a beta 2-selective adrenergic bronchodilator, in 8 asthmatic patients whose basal lung functions are almost within the normal range in both slow vital capacity (VC) and forced expiratory volume in one second (FEV1.0), and are free from asthmatic attack. In patients who had received procaterol 30 min after inhalation of aerosol, there was no significant change in VC, although FEV1.0, maximal expiratory flow at 50% VC (V50), maximal expiratory flow at 25% VC (V25) and maximal expiratory flow at 30% VC of partial maximal expiratory flow volume curve (V30p) improved significantly. On the other hand, in those who had received placebo, none of the parameters changed. Furthermore, R1 decreased and C0.5 increased significantly during the first 5 min after inhalation of procaterol aerosol. After an interval of 5 min, R1 did not change any further, while C0.5 continued to improve until 30 min after inhalation of procaterol. These results suggest that procaterol may first dilate the large airway and then may gradually dilate the small airway in bronchial asthma.

Adult