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Biomedical subjects

H Nogami

Publications and source records attributed to H Nogami.

At least 127 records · Page 7Linked to original sources

Reaction of hemoglobin with nitric oxide and nitrogen dioxide in mice.

The reaction of hemoglobin with NO and NO2 was compared in mice exposed to these cases. Nitrosyl hemoglobin (NOHb) and methemoglobin (MetHb) were determined simultaneously by electron spin resonance spectrometry at -140 degrees C. In mice exposed to 40 ppm NO, NOHb became constant (0.7%) in 30 min and declined rapidly with a half-life of several minutes when the mice were removed to room air. An increase of MetHb (5%) was also caused by exposure to NO and the time course was almost the same as that of NOHb. Exposure to 40 ppm NO2 produced only NOHb (0.2%); MetHb did not increase. The time course of NOHb was identical to that observed with NO exposure. Dose-effect relationships were determined with both gases at concentrations ranging from 20 to 80 ppm. A linear relationship could be observed between the concentrations of the gases and NOHb, but NO produced more NOHb than did NO2. There was an exponential increase of MetHb, particularly at high concentrations of NO.

Animals↗

Immunohistochemical characterization of pituitary stellate cells in rats.

Pituitary stellate cells from the normal adult male rats were immunohistochemically investigated at the light microscopical level by the use of rat TSH-beta, porcine ACTH1-39, porcine ACTH17-39, rat FSH and ovine FSH antisera. They were characterized by the stellate shape and a mimic engulfment of acidophils. In the present study, they were identified to be the ACTH cells but some were TSH cells. Although most of the corticotrophs showed a peripheral fringe immunostained with the porcine ACTH17-39 antiserum, some others were stained diffusively throughout the cytoplasm. The latter cells coincided, in shape and in homogenous stainability of the cytoplasm, with the stellate TSH cells. Both cells did not correspond but were independent in distribution at the same site of the gland on the adjacent two sections. The stellate type of FSH cells could react with the ovine FSH antiserum, but not with the rat FSH antiserum. Absorption tests of the ovine FSH, procine ACTH1-39 and procine ACTH17-39 antisera were carried out by an application of procine ACTH. In consequence, the porcine ACTH)-39 and porcine ACTH17-39 antisera were absorbed efficaciously by the ACTH antigen at the dose of 10 micrograms/ml, but the ovine FSH antiserum was not enough absorbed by ACTH in the doses of less than 1 mg/ml. It was not finally concluded whether or not the single stellate cells produced ACTH and FSH.

Adrenocorticotropic Hormone↗

Solubilized bone morphogenetic protein (BMP) from mouse osteosarcoma and rat demineralized bone matrix.

A selection of proteins including bone morphogenetic protein (BMP) was extracted in a disaggregated form from Dunn osteosarcoma or rat demineralized bone matrix by 4M guanidine hydrochloride (GuHCl) solution without losing its biological activity. The GuHCl extracts of Dunn osteosarcoma were divied into 4 different fractions by cesium chloride (CsCl) density gradients. Under a dissociative condition, the highest new bone yield was obtained in the low dense top one-third fraction, and BMP acitivity declined with increase in the density of each fraction. No BMP potential was observed in the surface-gel fraction under dissociative conditions. Under an associative condition (low GuHCl concentrations), BMP activity appears in the surface-gel fraction, while under a dissociative condition (high concentrations of GuHCl) BMP appears in the fraction below the surface gel. These facts suggest that under associative conditions, BMP aggregates with other low dense proteins in the surface-gel fraction and that this may be the state of aggregation of BMP in cells and matrix in nature. Present observations support the assumption that BMP is a relatively low density protein and excludes the idea of BMP activity in the collagen molecule, per se. A specific protein, with an apparent molecular weight of 63,000 daltons, is present in all fractions that exhibit BMP activity, and absent in fractions that do not exhibit this activity. BMP is not species-specific; rat BMP induces bone formation in mice. CsCl density-gradient centrifugation is an efficient tool for further purification and isolation of BMP.

Animals↗

Proteochondroitin sulfate synthesized in cartilages induced in vivo and in vitro by bone matrix gelatin.

Implanted allogeneic demineralized bone matrix gelatin induced sequential development of cartilage and bone in the recipient rat muscle tissue. Proteoglycans of the implants labeled in vivo with [35S]sulfate at different stages of development were analyzed by sucrose density gradient centrifugation. The major proteoglycan synthesized in day-5 implant, just prior to onset of chondrogenesis, was a dermatan sulfate-containing proteoglycan with relatively slow sedimentation rate. Additionally, a small amount of a faster sedimenting component could be detected. The faster sedimenting proteoglycan, in which chondroitin 4-sulfate accounted for 85% of total radioactivity, became predominant in day-10 sample when cartilage formation was maximal. By day 30, when cartilage had been replaced by newly formed bone, the synthesis of this faster sedimenting component had ceased. A similar, if not identical, proteoglycan was found to be a major one synthesized by the in vitro-induced cartilage. This proteoglycan was smaller in overall size and shorter in length of its chondroitin sulfate chains than a major proteoglycan component obtained from neonatal rat epiphyseal cartilage. Concurrent with these changes in proteoglycan type, there appeared to be a change in collagen type, since type II collagen, in addition to type I collagen, was synthesized in day-10 implant. These results indicate that the proteoglycan can be used as a molecular marker for chondrogenesis by bone matrix gelatin.

Abdominal Muscles↗

Kinky hair disease. Biochemical, histochemical, and ultrastructural studies.

The biosynthetic activities of protein and collagen from the patient of kinky hair disease, were reduced to 70 and 50%, respectively, compared with control. In tissue cultures, fast-green FCF staining coarse granules were found in the cytoplasm of skin fibroblasts from the patient. Ultrastructurally, collagen fibrils by iliac cartilage biopsy were irregular in width. Ruthenium red staining granules, presumed to be proteoglycans in the cartilage matrix, were relatively small in size and few in number. Chondrocytes showed poor development of organelles and relatively small glycogen accumulation.

Brain Diseases, Metabolic↗

Ultrastructure of cartilage in heritable disorders of connective tissue.

Ultrastruct of cartilage were examined in Marfan syndrome, Menkes kinky hair syndrome, achondroplasia, asphyxiating thoracic dysplasia, mild diastrophic dysplasia and mucopolysaccharidoses I and III. Ruthenium red staining revealed decrease of proteoglycans in cases with Marfan syndrome and kinky hair syndrome, and increase in cases with osteochondrodysplasia and mucopolysaccharidosis III. This morphologic tendency coincided with the result obtained by biochemical analysis of glycosaminoglycan contents in cartilage matrix from cases with Marfan syndrome (decreased content) and asphyxiating thoracic dysplasia (increased content). It was postulated that proteoglycan content in cartilage matrix might be related to excessive or reduced skeletal growth in Marfan syndrome or osteochondrodysplasia.

Achondroplasia↗

Studies on the biological effects of nitrogen oxides and photochemical oxidants.

The animal studies in mice resulted as follows. Long-term exposure to NO2 at or above 0.5 ppm affected primarily the respiratory organs. The pulmonary effect of NO was slighter than NO2. Nitrosylhemoglobin formation in vivo was much smaller than in vitro strong affinity of NO with hemoglobin. The components other than O3 contained in the photochemically formed oxidant mixtures enhanced the effect of O3 alone. Symptoms of the patients seriously injured by photochemical smog in Japan suggested the different type in quality from the Los Angeles-type smog.

Air Pollution↗

Limb anomalies produced by 2,2'-dipyridyl in rats.

The teratogenicity of 2,2'-dipyridyl (DIP), a chelator for ferrous iron, was investigated by administration of single dose of 60 or 75 mg/kg intraperitoneally to pregnant SD rats on days 11.5-14.5. Fetuses examined on day 21 were decreased in weight, and had defects chiefly in the limb. The type and incidence of limb defects differed according to day of treatment. Digital malformations in the forelimb and long-bone defects in the hindlimb were produced with high incidence by treatment on day 12.5, and the frequency of digital malformations in the hindlimb was increased by treatment on day 13.5. Light and electron microscopic examinations revealed the delay of mesenchymal condensation and destruction of mesenchymal cells in the forelimb bud in the early stage after day 12.5 treatment. The normal increase of DNA, protein, collagen and glycosaminoglycan contents in the forelimb bud was markedly inhibited by the treatment. The incorporation activities for [14C]proline and [14C]glucosamine of the forelimb bud were reduced to 50-60% of the control. These results indicate that DIP has potent teratogenic and cytotoxic effects on the development of the rat limb bud.

2,2'-Dipyridyl↗

Experimental myositis ossificans: cartilage and bone formation in muscle in response to a diffusible bone matrix-derived morphogen.

Bone matrix gelatin, prepared by chemical extraction of soluble noncollagenous proteins, was half digested with a chromatographically purified collagenase. The residue was placed on one side and autologous muscle on the other side of cellulose acetate membranes in diffusion chambers and tissue cultures. In this avascular system, the muscle septa connective tissue proliferated and differentiated into cartilage. Muscle tissue cultured in media conditioned with matrix residues and then transferred into a vascularized muscle pouch differentiated into cartilage and bone. These observations form the basis for a working hypothesis that myositis ossificans is a response of new populations of proliferating intramuscular connective tissue cells to a bone matrix-derived diffusible molecule.

Animals↗

Ultrastructure of chondrogenetic interactions between bone matrix gelatin and mesenchymal cells.

The ultrastructure of post fetal chondrogenesis was investigated in chondrogenetic implants and explants of bone matrix gelatin: (A) in direct contact with living cells; (B) separated from living cells by cellulose acetate membranes; (C) in serum or in a culture medium with no contact with living cells. Ruthenium red (RR) staining coarse granules free of interconnecting filaments aggregated in interstitial fluid and inside the surface of the bone matrix gelatin within 72 hours in systems with either direct or indirect contact with living connective tissue cells. No RR granules formed when control denatured or autolysed bone matrix gelatin were substituted for undenatured bone matrix gelatin. No RR granules formed in bone matrix gelatin incubated in serums or media in the absence of living cells in the system. These observations suggest the possibility that 4 days before overt transmembrane cartilage cell differentiation, covert (presumptive) chondroblasts synthesize and secrete precursor substance for aggregation of filament-free RR granules. The relationship between chondromorphogenesis and filament-free RR granules requires further investigation.

Animals↗

Glycosaminoglycans in congenital pseudarthrosis.

Light and electron microscopic studies on cells and matrices of congenital pseudarthrosis of the femur of a 5.5-year-old male revealed three areas with different morphological features; a fibrous area, a cartilaginous area and an osseous area. Glycosaminoglycans were isolated from each of the three areas and characterized by the degradation with chondroitinases. Although chondroitin sulfate was the major component in all regions, a significant amount of dermatan sulfate occurred in the fibrous area. A small amount of hyaluronic acid was found in both fibrous and osseous areas. These suggest that the peculiar composition of glycosaminoglycans in the affected part may account for some clinical aspects of the disease which resists treatment.

Child, Preschool↗

Transmembrane bone morphogenesis across multiple-walled diffusion chambers. New evidence for a diffusible bone morphogenetic property.

Bone generation and regeneration are associated with a bone morphogen that recruits mesenchymal cells for differentiation into bone. Experiments with particulate bone matrix gelatin implanted in multiple-walled diffusion chambers suggest that bone morphogen is a rapidly diffusible molecule, and consists of a noncollagenous bone morphogenetic protein (BMP). When particulate bone matrix gelatin is implanted inside of diffusion chambers constructed of two to five membranes, ranging from 300 to 750 cu micronm in total thickness, large deposits of bone develop on the outside. The volumes of the deposits of new bone are inversely proportional to the thickness (or distance) of transmission of the BMP. Transmission for long distances through interstitial fluid can be accounted for by a low molecular mass hydrophobic BMP, disseminated according to the laws of diffusion.

Animals↗

Congenital kyphoscoliosis and spinal cord lesion produced in the rat by beta-aminopropionitrile.

Pregnant rats received the lathyrogen beta-aminopropionitrile (1,500 mg/kg) intraperitoneally on day 16 (plug day = 0 day). Kyphoscoliosis was produced in a high incidence in the fetuses at the level of the upper thoracic spine as early as 24 hours after treatment. Although most of the affected newborns died within two weeks, survivors were studied until 20 weeks after birth. Survivors developed paraplegia in consequence of kyphoscoliosis. Both spinal deformity and motor disturbance were progressive. Biochemical and electron microscopic observations suggested that beta-aminopropionitrile treatment resulted in an inhibition of collagen formation in the spinal column and surrounding longitudinal ligaments of the fetuses six hours after the treatment. In addition, electron micrographs of vertebral bodies showed a decrease of proteoglycan granules in the extracellular matrix. Therefore, rupture and collapse of weakened ligaments and vertebral bodies might result in severe spinal deformity and spinal cord lesion.

Abnormalities, Drug-Induced↗

An osteosarcoma cell and matrix retained morphogen for normal bone formation.

Histophysiology, ultrastructure, chemical analyses of transplants and implants of Dunn and Ridgway mouse osteosarcomas demonstrate that tumorigenesis is a manifestation of deranged morphogenesis in developing mesenchymal cell populations. The end product of development is defective, incompletely calcified, disorganized bone without any inclusions of bone marrow tissue. When Dunn osteosarcoma is freeze-dried and then implanted, the tumor is resorbed and replaced by deposits of normal cartilage, bone, and bone marrow. Freeze-dried Ridgway osteosarcoma is replaced only by a fibrous connective tissue scar. Disaggregated Dunn tumor osteoblasts synthesize a trypsin-labile collagenase-resistant cell surface localized bone morphogen. Tumor matrix stroma, prepared by sequential chemical extraction of soluble non-collagenous proteins also contains significant quantities of the same bone morphogen. Tumor tissue pulverized to particle size as small as 44 micrometer3 transmitted bone morphogen more rapidly than intact tumor tissue. The total tumor cell and stroma mediated bone morphogen produces three times more normal bone than normal cortical bone matrix. Our working hypothesis is that a normal bone morphogenetic polypeptide (BMP) is synthesized by Dunn osteosarcoma cells and retained by the tumor matrix stroma. Neither the mechanism of transmission nor the mesenchymal cell receptor sites of BMP are known.

Alkaline Phosphatase↗

Clinical features and treatment of joint dislocations in Larsen's syndrome. Report of three cases in one family.

Of 3 cases of Larsen's syndrome in one family, one had bilateral dislocation of the hip and the knee joints. The knee joint was not reduced by manipulation and corrective cast, while both hip and knee joints were simultaneously reduced by skeletal traction of the tibia at the age of 4 months, and the course was satisfactory. Reduction of joint dislocations should be attempted by a conservative method such as skeletal traction as early as possible. Various radiographic skeletal abnormalities occurred in all 3 cases. Larsen's syndrome very likely has a genetic origin.

Abnormalities, Multiple↗