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Biomedical subjects

H Kobayashi

Publications and source records attributed to H Kobayashi.

At least 181 records · Page 10Linked to original sources

Adrenomedullin in the cerebral circulation.

The central nervous system requires an effective autoregulation of cerebral circulation in order to meet the critical and unusual demands of the brain. In addition, cerebral microvessels has a unique feature, the formation of the blood-brain barrier, which contributes to the stability of the brain parenchymal microenvironment. Many factors are known to be involved in the regulation of cerebral circulation and blood-brain barrier functions. In the last few years a new potential candidate, adrenomedullin, a hypotensive peptide was added to this list. Adrenomedullin has a potent vasodilator effect on the cerebral vasculature, and it may be implicated in the pathologic mechanism of cerebrovascular diseases. In this review, we describe current knowledge about the origin and possible role of adrenomedullin in the regulation of cerebral circulation and blood-brain barrier functions.

Adrenomedullin↗

Clinical features of symptomatic Rathke's cleft cyst.

To investigate the clinical features of Rathke's cleft cysts (RCCs), we retrospectively analyzed 15 cases with histologically confirmed RCCs. All patients underwent formal testing of visual field, endocrinological evaluation and magnetic resonance imagings. As overall presenting symptoms, endocrine disturbance was the most common symptoms, followed by visual disturbance and headache. Among the endocrine disturbances based on adenohypophysial dysfunction, hyperprolactinemia was most common. Considering the size of RCCs, RCCs could induce hyperprolactinemia only when the cysts became large enough to compress the infundibular system. Our series showed relative high incidence of pituitary dwarfism and diabetes insipidus (DI). These facts indicated that RCCs could evoke hyposecretion of growth hormone in young patients and DI in aged patients by direct compression of the pituitary gland in the early stage of progression. All cases who had headache had no other symptoms. We could not prove the evidence that RCCs could induce headaches in these cases. This might be suggested that headache could not be a sole symptom in cases of RCCs.

Adolescent↗

Susceptibility of thermally injured mice to cytomegalovirus infection.

Thermally injured patients are very susceptible to infection with cytomegaloviruses. In this study a role of burn-associated type 2 T cell responses on the cytomegalovirus infection was examined in a mouse model of thermal injury. A predominance of type 2 T cell responses in splenic lymphocytes of thermally injured mice has been previously demonstrated. SCID mice inoculated with splenic T cells from thermally injured mice were susceptible to infection with a small amount (5 PFU/mouse) of murine cytomegalovirus (MCMV). Conversely, SCID mice inoculated with splenic T cells from normal mice were resistant to the same infection. High levels of IL-4 and IL-10, but not IFN-gamma and IL-2, were detected in sera of thermally injured mice (TI-mice) infected with MCMV when those were compared with sera of normal mice infected with MCMV. IL-4 and IL-10 (type 2 cytokines) were produced by splenic T cells from MCMV-infected TI-mice, when they were stimulated in vitro with anti-CD3 mAb. Type 1 cytokines (IFN-gamma and IL-2), however, were not produced by these T cells after the same stimulation. In contrast, splenic T cells from MCMV-infected normal mice produced type 1 cytokines by the stimulation with anti-CD3 mAb. These results suggest that the susceptibility of mice to MCMV infection is markedly influenced by burn-associated type 2 T cell responses.

Adoptive Transfer↗

Selective expression of aquaporin 1, 4 and 5 in the rat middle ear.

The middle ear cavity is an air-filled space that must be maintained for effective sound transmission to the inner ear. To examine the mechanisms of water homeostasis in the middle ear, we investigated whether aquaporins (AQPs), a family of water-permeable channels, were expressed in the middle ear. Reverse transcription-polymerase chain reaction and immunoblot analyses revealed that mRNAs encoding AQP1, 4 and 5 (but not 2 or 3) subtypes were expressed in rat middle ear epithelium; AQP1, 4 and 5 were detected as 28-, 30- and 30-kDa proteins, respectively. Immunohistochemical analysis showed that AQP1 was localized at capillary endothelial cells and fibroblasts in lamina propria mucosae; AQP4 was present solely at the basolateral membrane of ciliated cells, whereas AQP5 was on the apical surface of ciliated cells as well as of flat and columnar epithelial cells. The characteristic different localizations of AQP1, 4 and 5 subtypes in the middle ear suggest that middle ear water homeostasis requires the coordinated operation of these AQPs.

Animals↗

Perilymph fistula--45 case analysis.

PURPOSE OF THE STUDY: Though perilymph fistula (PLF) is not a rare disease, preoperative diagnosis still remains to be established. Some new diagnostic methods are challenging, but there is still no established diagnostic method except exploratory tympanotomy that verifies the occurrence of leakage. Early diagnosis of PLF is fully depending on history taking and some clinical examinations. To know the clinical features of PLF is one of the greatest helps to make both earlier and accurate diagnosis. In spite of some innovations in clinical examinations classic diagnostic procedure is thought to be still reliable. PROCEDURES: We investigated the clinical symptoms, basic tests results and therapeutic results in patients with PLF. RESULTS: From 1983 to 1998 PLF was identified in 44 patients (45 ears) with exploratory tympanotomies in our hospital. With respect to clinical history the predisposing factors such as blowing the nose, lifting heavy goods, and landing in an airplane were found in almost half of the patients, while the rest of them had no clear inducing factors. Their major symptoms included hearing loss (93%), vertigo and dizziness (91%), tinnitus (76%), and aural fullness (31%). The patients who have a clear predisposing factor tended to make diagnosis easily; on the other hand the rest of the patients who do not have clear etiology had some diagnostic difficulty. Subjective positive fistula signs were observed in 71% of patients. Vestibular symptoms improved in 80% of patients after closure of PLF. CONCLUSIONS: These results suggest that the variety of clinical manifestation make diagnosis more difficult. At the moment meticulous clinical history taking and close follow-up applying repeating fistula tests are the most important for not only earlier but also accurate diagnosis.

Adolescent↗

Airway biofilm disease.

This paper describes the formation of biofilm, its characteristics, its effect on the host cells and treatment of the condition. The airway biofilm diseases are known to be intractable and persistent; also, auto-immune factors play a role in the development of the symptoms. The characteristic of airway biofilm diseases is of a harmful auto-immune reaction occurring along with the symptoms which are different from the simple acute infection interaction between microorganism and host in an acute airway infection.

Animals↗

Enhancement of the therapeutic outcome of radio-immunotherapy by combination with whole-body mild hyperthermia.

To enhance the effect of radio-immunotherapy for solid cancers, whole-body mild hyperthermia was added, and its effects on the pharmacokinetics of radiolabelled antibody, outcome of radio-immunotherapy, and radiosensitivity of the tumour were investigated. Nude mice bearing human colon cancer xenografts were heated to 40 degrees C for 3 or 6 h. After heating, mice received intravenous (i.v.) injections of [131I]-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody. Although 6-h heating did not alter the biodistribution of the radiolabelled antibody, and alone did not show any therapeutic effect on tumour growth, when combined with radio-immunotherapy, the therapeutic effect on tumour growth was significantly enhanced. Three-hour heating also significantly enhanced the effect of radio-immunotherapy. Colony formation assay showed that the radiosensitivity of the tumour was significantly enhanced after heating, which was achieved by a reduction of the hypoxic fraction of the tumour. In conclusion, the addition of whole-body mild hyperthermia significantly enhanced the therapeutic effect of radio-immunotherapy by increasing the radiosensitivity of the tumour.

Animals↗

Toxicity of coelomic fluid of the earthworm Eisenia foetida to vertebrates but not invertebrates: probable role of sphingomyelin.

The coelomic fluid (CF) of the earthworm Eisenia foetida exhibits a wide variety of biological activities. We found that the CF was not toxic to 42 species, belonging to seven invertebrate phyla, almost all in aquatic adults and larvae exposed to CF. Eleven teleostean species tested died in 0.2-1% CF mostly between 10 and 120 min and the effects were dose-dependent. Tadpoles of the toad Bufo japonicus formosus died in 0.4-2% CF between 80 and 225 min depending upon size, with larger tadpoles surviving longer. Before dying, all experimental tadpoles developed curled and shrunken tails. The Okinawa tree lizard, soft-shelled turtle, Japanese quail, mouse and rat all died after i.v. injection of CF (above 20 microl/kg). Thus, CF was not toxic to invertebrates, but toxic to vertebrates. After heating, CF lost its toxicity to fish, tadpoles and mice. Both CF and lysenin incubated with sphingomyelin-liposomes (SM-liposomes) were no longer toxic, suggesting the involvement of SM in the toxicity. Lysenin, which is a constituent of CF and known to bind specifically to sphingomyelin, exhibited toxicity similar to that of CF. Thus, lysenin in CF is probably responsible for the toxic effects of CF by binding to SM in vertebrate tissues. The bodies of invertebrates might contain little or no SM, while those of vertebrates do contain SM. The coelomic fluid of the earthworm Pheretima communissima has no toxicity to mouse.

Animals↗

A new macrocyclic trichothecene, 12,13-deoxyroridin E, produced by the marine-derived fungus Myrothecium roridum collected in Palau.

A new macrocyclic trichothecene, 12,13-deoxyroridin E (1), and three known compounds, roridin E (2), verrucarin A (3), and verrucarin J (4), were obtained as cytotoxic components from the marine-derived fungus Myrothecium roridum, isolated in Palau. 12,13-Deoxyroridin E is the second example of a macrocyclic trichothecene possessing a double bond at C-12-C-13 and was about 80-fold less cytotoxic than roridin E, the epoxide variant.

Animals↗

Cytotoxic effects of soluble factor in preeclamptic sera on human trophoblasts.

Evidence indicating abnormal biological behavior of trophoblasts has been seen in preeclamptic patients, but the mechanism is still unknown. We have previously shown that endothelial injury and neutrophil activation are induced by certain factors in preeclamptic sera. We investigated the effect of sera from eight preeclamptic and 11 normal pregnant women on cellular proliferation and viability of trophoblasts using 3H-thymidine incorporation and the trypan-blue dye exclusion test, respectively. Five of eight preeclamptic sera, but none of the normal pregnant sera, inhibited 3H-thymidine incorporation. The trypan-blue test revealed the sera reduced cellular viability. Gel permeation showed that the greatest growth-inhibitory activity corresponded to a molecular weight of 50 kDa. The serum-mixing test revealed this permeation and inhibitory preeclamptic sera suppressed the growth-promoting activity of normal pregnant sera in a dose-dependent manner. These results suggested the presence of certain factors in some preeclamptic sera that can affect cellular behavior of human trophoblasts.

Adult↗

Heterogeneous increases of cytoplasmic calcium: distinct effects on down-regulation of cell surface sodium channels and sodium channel subunit mRNA levels.

1. Long-term (> or = 12 h) treatment of cultured bovine adrenal chromaffin cells with A23187 (a Ca(2+) ionophore) or thapsigargin (TG) [an inhibitor of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)] caused a time- and concentration-dependent reduction of cell surface [(3)H]-saxitoxin (STX) binding capacity, but did not change the K:(D:) value. In A23187- or TG-treated cells, veratridine-induced (22)Na(+) influx was reduced (with no change in veratridine EC(50) value) while it was enhanced by alpha-scorpion venom, beta-scorpion venom, or Ptychodiscus brevis toxin-3, like in nontreated cells. 2. The A23187- or TG-induced decrease of [(3)H]-STX binding was diminished by BAPTA-AM. EGTA also inhibited the decreasing effect of A23187. A23187 caused a rapid, monophasic and persistent increase in intracellular concentration of Ca(2+) ([Ca(2+)](i)) to a greater extent than that observed with TG. 2,5-Di-(t-butyl)-1,4-benzohydroquinone (DBHQ) (an inhibitor of SERCA) produced only a rapid monophasic increase in [Ca(2+)](i), without any effect on [(3)H]-STX binding. 3. Reduction in [(3)H]-STX binding capacity induced by A23187 or TG was attenuated by Gö6976 (an inhibitor of conventional protein kinase C) or calpastatin peptide (an inhibitor of calpain). When the internalization rate of cell surface Na(+) channels was measured in the presence of brefeldin A (an inhibitor of vesicular exit from the trans-Golgi network), A23187 or TG accelerated the reduction of [(3)H]-STX binding capacity. 4. Six hours treatment with A23187 lowered Na(+) channel alpha- and beta(1)-subunit mRNA levels, whereas TG had no effect. 5. These results suggest that elevation of [Ca(2+)](i) caused by A23187, TG or DBHQ exerted differential effects on down-regulation of cell surface functional Na(+) channels and Na(+) channel subunit mRNA levels.

Animals↗

Chromosomal instability in chromosome band 12p13: multiple breaks leading to complex rearrangements including cytogenetically undetectable sub-clones.

During fluorescence in situ hybridization (FISH) analysis of metaphase cells from 70 patients with lymphoid and myeloid hematologic malignancies and chromosomal rearrangements involving band 12p13, we identified nine patients (four with lymphoid malignancies, four with myeloid malignancies and one with biphenotypic leukemia) who showed more complicated rearrangements than we had expected from conventional cytogenetic study. In six patients, multiple breaks occurred in small segments of 12p with subsequent translocations and insertions of these segments into other chromosomes, sometimes to unexpected regions. In three patients additional chromosome breaks resulted in a sub-clone which was cytogenetically indistinguishable from the main clone in each patient based on the cytogenetic analysis. These subtle molecular events were detected exclusively in a region covering TEL/ETV6 and KIP1/CDKN1B. Seven of nine had a previous history of chemo/radiotherapy; all the patients showed complex karyotypes, even though they were newly diagnosed with leukemia. Survival data were available in five patients, and all survived less than 6 months. These findings suggest that the 12p13 region, especially the above-mentioned region, is genetically unstable and fragile. It is likely that multiple chromosome breaks were induced through mutagens used in chemo/ radiotherapy, and are associated with a sub-group of patients with an extremely bad prognosis.

Chromosome Fragility↗

Resorption of the lateral pole of the mandibular condyle in temporomandibular disc displacement.

OBJECTIVES: To assess the possible relationship between resorption of the superolateral pole of the mandible condyle (RSLC) and TMJ disk displacement. METHODS: Two hundred and seventeen TMJs in 138 patients were studied. Displacement of the disc, degree of displacement and disc configuration were assessed using MRI. RSLC was assessed from a transorbital radiograph. RESULTS: Seventy-two joints (37%) were considered to have RSLC. A significantly higher prevalence of RSLC was found in joints with disc displacement (goodness test of fit for chi-square, P<0.05). A significantly higher prevalence of RSLC was found in joints with advanced disc displacement and advanced disk deformation (Mann-Whitney U-test, P<0.01). CONCLUSIONS: RSLC appears more likely to occur in joints with advanced disc displacement.

Adolescent↗

A study of the relationship between the position of the condylar head and displacement of the temporomandibular joint disk.

OBJECTIVES: To examine the possible relationship between condylar position and disk displacement in the TMJ. METHODS: Forty-eight joints with no disk displacement (NDD), 84 joints with a reducible displaced disk (RDD) and 99 joints with a permanently displaced disk (PDD) were selected. The positions of the condyle and TMJ disk were calculated from lateral MR images. RESULTS: There were significant differences in condylar position between the joints with NDD and RDD, while there was no difference between those with NDD and PDD (Kruskal-Wallis and post-hoc test, P<0.05). There was also a significant correlation between the position of the condylar and the displaced disk (Spearman's rank correlation, P<0.05). The condyle was located more anteriorly with advancing disk displacement. CONCLUSIONS: We suggest that if the disk displacement is slight, the condyle is displaced posteriorly: as the disk displacement becomes more severe (i.e. more anteriorly displaced), the condyle returns to the concentric position.

Adolescent↗

Environmental effects on the functions of the stratum corneum.

The stratum corneum (SC) is such an efficient barrier that only 2-5 g per h per cm2 of transepidermal water loss (TEWL) occurs in normal skin. The SC also plays another important role at the skin surface in keeping our skin smooth and flexible by binding water. We exposed a simulation model of in vivo SC to various, excessive physical insults in vitro, such as irradiation with 1 J per cm2 of UVB, 50 J per cm2 of UVA, or 3000 rad of X-ray, heating at 90 degrees C for 3 min, freezing at -196 degrees C for 60 s or repeated placement in an extremely dry or humid condition. None of them could cause any permanent change in the SC functions. Only the application of chemical agents such as lipid solvents or a detergent or the affliction of trauma resulted in a functional derangement of the SC. Because the viable skin tissues are more vulnerable to the effects of the environment than the SC, most of the abnormalities of the SC functions developing after environmental insults are secondarily caused by enhanced epidermal proliferation induced under the influence of underlying inflammation. These functional abnormalities were found to be demonstrable with biophysical measurements long after the disappearance of skin redness, the clinically observable sign of inflammation. The SC abnormalities in inflamed skin are also detectable as a change in the content of chemical mediators. For example, the ratio between proinflammatory IL-1 and its receptor antagonist (IL-1ra) whose production by epidermal keratinocytes is markedly enhanced by various proinflammatory stimuli, showed a deviation towards an excess of the latter in inflammatory skin. Facial skin that is always exposed to the environment is unique in that its SC shows such a deviation in the IL-1/IL-1ra ratio suggestive for the presence of mild inflammation even in normal individuals.

Dermatitis↗

A new case of alpha-N-acetylgalactosaminidase deficiency with angiokeratoma corporis diffusum, with Ménière's syndrome and without mental retardation.

alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described. We report a further case in a 47-year-old Japanese woman, the product of a consanguineous marriage. The remarkable findings in this patient were her normal intelligence, Ménière's syndrome, disturbance of peripheral sensory nerves, hearing loss and cardiac hypertrophy. alpha-NAGA enzyme activity in her plasma was 0.77% of the normal value. Other enzyme activities, such as alpha-galactosidase, beta-galactosidase, alpha-L-fucosidase, beta-mannosidase and aspartylglucosaminidase, were within normal limits. A large quantity of amino acid O-glycans was detected in her urine. Gene analysis revealed a novel point mutation (G-->A transition) at nucleotide 11018 (986 in the cDNA) resulting in an Arg-329-Gln substitution. Kanzaki disease has the same enzyme defect as Schindler disease, but the manifestations are quite different.

Fabry Disease↗

Kikuchi's disease and the skin: case report and review of the literature.

We report scattered indurated erythematous lesions that presented in an 18-year-old Japanese man with Kikuchi's disease (KD; histiocytic necrotizing lymphadenitis). A skin biopsy showed a proliferation of histiocytes and abundant nuclear debris without the presence of neutrophils, which is characteristic of KD. The specific dermatological and pathological details of KD have been yet to be fully described. In order to assess the typical skin features of KD better, we have reviewed all the previously well-documented reports of such lesions. As the clinical and histopathological cutaneous findings in KD are so heterogeneous, it is important that scattered indurated erythematous lesions should be included as one of the possible cutaneous manifestations of this disease.

Adolescent↗