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Biomedical subjects

M Yamagata

Publications and source records attributed to M Yamagata.

At least 91 records · Page 5Linked to original sources

Eosinophilic keratoconjunctivitis in seven horses.

Eosinophilic keratoconjunctivitis was diagnosed in 7 horses at The Ohio State University between 1976 and 1994. All horses had moderate-to-severe blepharospasm, chemosis, and conjunctival hyperemia; epiphora; and extensive yellow-to-white caseous mucoid discharge. Corneal ulcers associated with this disease were perilimbal and extended centrally. All ulcers were covered with a white necrotic plaque firmly attached to the underlying cornea. Other ophthalmic abnormalities were not detected. Corneal scrapings examined cytologically contained numerous eosinophils interspersed between epithelial cells, few mast cells, and neutrophils. Microbial organism were not seen. Bacterial and fungal cultures were negative for ocular pathogens. The initial diagnosis of eosinophilic keratoconjunctivitis was made on the basis of clinical and cytologic findings. In 5 horses, the condition completely resolved after topical treatment with corticosteroid (0.05% dexamethasone) and triple antibiotic ointments. However, the duration of treatment was prolonged, with a mean treatment time of 64 days (range, 45 to 106 days). All corneal ulcers remained superficial, and despite the prolonged duration of treatment, none of the horses developed secondary bacterial or fungal keratitis. One horse underwent superficial keratectomy and had the shortest resolution time (14 days).

Administration, Topical↗

Visual projection map specified by topographic expression of transcription factors in the retina.

Topographical maps of neuronal connectivity occur in various brain regions. In the visual system of birds, retinal ganglion-cell axons from the anterior retina connect to a posterior part of the optic tectum, and posterior retinal axons connect to the anterior part, thereby establishing a point-to-point projection map. The chemoaffinity theory predicts that the orderly retinotectal projection is generated by a topographical arrangement of molecules. We report here that we have found several genes topographically expressed along the nasotemporal (anterior-posterior) axis in the embryonic chicken retina. Among these, two transcriptional regulators, belonging to the winged-helix family are expressed in a mutually exclusive manner in either the nasal or temporal part of the retina. Misexpression of each factor causes misprojection on the tectum along the rostrocaudal axis, showing that topographical expression of these transcription factors controls formation of the retinotectal map.

Alkaline Phosphatase↗

Sensory innervation to the anterior portion of lumbar intervertebral disc.

STUDY DESIGN: The level of dorsal root ganglia that receives sensory afferent nerves from the anterior portion of the lower lumbar intervertebral disc was investigated in rats using a retrograde transport method. OBJECTIVES: Sometimes patients with lower lumbar disc lesions complain of inguinal pain that does not correspond to the dermatome of the injured nerve roots. To investigate the origin of the pain, the authors studied the sensory innervation to the anterior portion of the lumbar intervertebral disc. SUMMARY OF BACKGROUND DATA: The innervation to the posterior portion of the lumbar disc has been extensively investigated and has been reported to be segmental. However, little is known about the nerve supply to the anterior portion of the lumbar disc. METHODS: The retrograde transport method was used in rats. As tracers, horseradish peroxidase and choleratoxin B subunit were used. Horseradish peroxidase crystals were placed on the anterior portion of the L5-L6 disc, and choleratoxin B subunit was injected into the L5-L6 disc. The bilateral dorsal root ganglia were histologically examined. RESULTS: Labeling of L1 and L2 dorsal root ganglia neurons was recognized. No neurons were labeled in dorsal root ganglia of other levels, including the segmentally corresponding L5. CONCLUSIONS: Using the retrograde transport method, the authors demonstrated that the anterior portion of the L5-L6 lumbar intervertebral disc was innervated from L1 or L2 spinal nerves in rats. These results appear to explain the reason why patients with lower lumbar disc lesions sometimes complain of inguinal pain corresponding to the L1-L2 dermatome.

Animals↗

Postoperative recurrence of solitary small hepatocellular carcinoma.

The prognosis of hepatocellular carcinoma after hepatic resection remains poor. The major cause is postoperative recurrence, most frequently intrahepatic. During the past 7 years, we conducted a detailed study of recurrence after hepatectomy in 34 patients with solitary small hepatocellular carcinoma measuring no larger than 4 cm in diameter, in which 13 cases had postoperative recurrent tumors, and two cases were considered multicentric. Eighty-five percent of recurrences were diagnosed at 6-18 months after the operation. The cumulative recurrence rates were 61% at 5 years after operation. When analyzing the factors affecting recurrence, a significant difference was observed regarding tumor diameter. After recurrence, most patients underwent percutaneous ethanol injection treatment and/or transcatheter arterial chemoembolization and lipiodolization. Four patients died of progressive disease within 1 year after recurrence; the treatment thus seemed to have no effect. The other patients with recurrence remain alive with the disease. The overall cumulative survival rates in this series were 76% at 3 years and 60% at 5 years after operation. To obtain better results after hepatectomy, even for small hepatocellular carcinoma, careful, long-term follow-up evaluation is therefore necessary for the multidisciplinary treatment of the postoperative recurrence, as well as the early diagnosis of tumors in high-risk patients.

Adult↗

Comparison between menopause-related changes in bone mineral density of the lumbar spine and the proximal femur in Japanese female athletes: a long-term longitudinal study using dual-energy X-Ray absorptiometry.

This longitudinal study examined whether bone mineral density (BMD) of the lumbar spine and the proximal femur is maintained in pre-, peri-, and postmenopausal women by regular exercise. BMD was measured using dual-energy X-ray absorptiometry (DXA). Twenty-six Japanese women (mean age 47.8 years) were followed 4-5 years. Twenty-two subjects from volleyball or jogging clubs had participated in the same exercise for more than 5 years at the initial BMD measurement. Longitudinally, for these 22 athletes, the rate of change per year in BMD of the lumbar spine was -0.17% in the premenopause group and -2.60% in the perimenopause group. In the proximal femur of the athletes, BMD increased (rate of increase per year 1.80%) in the premenopause group, but decreased (rate of decrease per year 1.07%) in the perimenopause group. In the premenopause group, BMD of the proximal femur increased in all athletes. However, in the proximal femur, the nonexercise group showed a 0.31% decrease, a significant difference (P < 0.05) compared with the athletes. These findings suggest that women can achieve continuous gains in bone mass in the proximal femur before menopause by regular intense exercise. However, continued high-level physical activity in the perimenopausal women was not able to prevent bone loss.

Absorptiometry, Photon↗

The chronic administration of drugs that inhibit the regulation of intracellular pH: in vitro and anti-tumour effects.

Mean values of extracellular pH (pHe) in tumours tend to be about 0.5 pH units lower than in normal tissues, whereas values of intracellular pH (pHi) in tumours and normal tissues are similar. Previous studies have shown that drugs that acidify cells at lower pHe such as nigericin, used alone or with agents that inhibit the regulation of pHi, have toxicity to cultured cells at pHe < 6.5 in short-term exposure; these agents also lead to modest anti-tumour effects in mice when given acutely. To evaluate the long-term effects of these drugs at levels of pHe that might occur commonly in tumours, we exposed cells for up to 72h at pHe 6.8 or 7.2 in vitro. Nigericin (0.033 microM) caused time-dependent cell killing of murine KHT and EMT-6 cells at pHe 6.8 (but not at pHe 7.2) with a surviving fraction approximately 5 x 10(-3) after 72 h exposure. Cell killing was increased in the presence of 4,4-diisothiocyanstilbene 2,2-disulphonic acid (DIDS), an inhibitor of Na+-dependent HCO3-/CI- exchange, and to a lesser extent in the presence of 5-(N-ethyl-N-isopropyl) amiloride (EIPA), an inhibitor of Na+/H+ exchange. Cell killing was exquisitely sensitive to the level of pHe. Osmotic pumps were used to obtain a 72 h continuous infusion of nigericin in mice; this led to dose-dependent killing of cells in KHT tumours with surviving fraction of approximately 0.1 at maximum tolerated doses. Hydralazine, which may cause tumour hypoxia and lower pHi as well as pHe, caused cytotoxity when given alone by chronic infusion, and enhanced the cytotoxicity due to nigericin. The addition of DIDS and/or EIPA (using two pumps) further enhanced anti-tumour toxicity, with a surviving fraction of approximately 0.002 at tolerated doses of the four drugs used to treat KHT tumours. The experiments demonstrate the activity of drugs that inhibit the regulation of pHi against murine tumours when delivered by chronic infusion.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Identification of novel missense mutations (Phe310Leu and Gly439Arg) in a neonatal case of hypophosphatasia.

Hypophosphatasia is associated with a defect of the tissue-non-specific alkaline phosphatase gene. We performed a mutational analysis in a surviving patient diagnosed at birth as having hypophosphatasia, on the basis of a low level of serum alkaline phosphatase (ALP) activity and characteristic radiographical findings. She had two sisters, one of whom died of respiratory failure complicated by perinatal hypophosphatasia; the other seemed healthy, with a relatively low activity level of ALP. The patient's parents also had low ALP activity. Sequence analysis of the tissue-nonspecific alkaline phosphatase gene was performed, using genomic DNA and total RNA from the skin fibroblasts of the patient and the peripheral mononuclear cells of her parents. The conversion of Phe to Leu at codon 310 (F310L) and Gly to Arg at 439 (G439R) were identified in the patient. Interestingly, the reconstructive experiments demonstrated that the F310L mutant exhibited an ALP activity level 65% of the normal level, whereas the mutant G439R had no activity. Moreover, the digestion by StuI, after a PCR using complementary DNA extracted from fibroblasts of the patient and lymphocytes of her father, revealed a relatively low messenger RNA level of F310L. These findings suggest that the neonatal case of hypophosphatasia was associated with compound mutations, one of which caused the loss of ALP activity and the other of which caused a slight reduction of the ALP activity, with a relatively low level of messenger RNA.

Adult↗

[Measurement of the common carotid arterial flow during parabolic flight in the anesthetized rat].

To measure the blood flow of a common carotid artery (CCA) during parabolic flight in the rat, we developed an animal double hold box (ADHB) made of styrene expanded form for the anesthetized rat to keep the animal at a proper posture in an aircaft. Twelve anesthetized rats weighing 291-342 g were surgically operated to mount a ultrasound flowmeter probe (1 mm size,1RS:Transonic Systems Inc.) around the right CCA and to insert a catheter into the right axillar artery for blood pressure measurement. These animals were held comfortably in ADHBs which were placed on the rack installed in the aircraft (MU-300). A total of 27 parabolic flights was performed and the blood flow was measured accurately in 9 rats. This special animal holding facility is useful for various types of animal experiments in an aircraft.

Animals↗

The afferent pathways of discogenic low-back pain. Evaluation of L2 spinal nerve infiltration.

The afferent pathways of discogenic low-back pain have not been fully investigated. We hypothesised that this pain was transmitted mainly by sympathetic afferent fibres in the L2 nerve root, and in 33 patients we used selective local anaesthesia of this nerve. Low-back pain disappeared or significantly decreased in all patients after the injection. Needle insertion provoked pain which radiated to the low back in 23 patients and the area of skin hypoalgesia produced included the area of pre-existing pain in all but one. None of the nine patients with related sciatica had relief of that component of their symptoms. Our findings show that the main afferent pathways of pain from the lower intervertebral discs are through the L2 spinal nerve root, presumably via sympathetic afferents from the sinuvertebral nerves. Discogenic low-back pain should be regarded as a visceral pain in respect of its neural pathways. Infiltration of the L2 nerve is a useful diagnostic test and also has some therapeutic value.

Adolescent↗

[TCR alpha beta + CD4- CD8- T cells among the peripheral blood mononuclear cells of myasthenia gravis patients].

We investigated the occurrence of TCR alpha beta + CD4- CD8- mononuclear cells (DN alpha beta T cells) and TCR gamma delta + CD3+ mononuclear cells (gamma delta T cells) among the peripheral blood mononuclear cells of 22 myasthenia gravis patients (MG) and 22 controls in order to examine whether extrathymic T cell subpopulations might be responsible for the pathogenesis of MG. The differences between the mean percentages of both DN alpha beta T cells and gamma delta T cells in the MG patients (DN alpha beta T cells: 0.53 +/- 0.51%, gamma delta T cells: 3.45 +/- 2.79%) and the controls (DN alpha beta T cells: 0.32 +/- 0.16%, gamma delta T cells: 3.81 +/- 2.36%) were not significantly different. However, higher DN alpha beta T cells ratios (1.48 approximately 1.84%) were noted in three MG patients. Thymectomy and subsequent thorough dissection of the anterior mediastinum 3 years after thymectomy had no effect on the symptoms of one patient, a 25-year-old woman without thymoma. The other two patients, a 45-year-old man and a 41-year-old woman without thymoma, had recurrences despite long-term remissions (14 years and 30 years, respectively) after thymectomy. Examination of DN alpha beta T cells, which are probably generated extrathymically without negative selection, may play an important role in understanding the pathogenesis in these three cases of MG.

Adult↗

[A case of lung metastasis from breast cancer successfully treated by FLEP (5-FU leucovorin, etoposide CDDP) combined arterial infusion chemotherapy].

A 33-year-old woman had undergone left mastectomy after diagnosis of breast cancer. One year after operation, multiple lung metastasis was confirmed by chest X-ray and CT scan. The patient received 6 courses of cyclophosphamide, epirubicin, and 5-FU (CAF) combined chemotherapy. However, the lesions were increased and the result of this chemotherapy was judged to be "progressive disease" (PD). A catheter was placed in the thoracic aorta, and FLEP combined intraaortic infusion chemotherapy was performed. The patient received 4 courses of 5-FU (325/mg/m2/day, civ, on day 1-5), leucovorin (30 mg/body/day, iv, on day 1-5), etoposide (60/mg/m2/day, ia, on day 7 and day 21), cisplatin (60/mg/m2/day, ia on day 7 and 21) every 4 weeks. The multiple lung metastasis almost disappeared on chest examination, and found to be less than 1 cm in diameter on CT scan. This result suggests FLEP combined chemotherapy is effective as a second-line treatment of recurrent breast cancer.

Adult↗

Effects of age on messenger RNA expression of glucocorticoid, thyroid hormone, androgen, and estrogen receptors in postmortem human hippocampus.

We studied messenger RNA (mRNA) expressions of receptors for glucocorticoid (GR), thyroid hormone (TR), androgen (AR), and estrogen (ER) and their changes with age in the hippocampal subregions in postmortem human brain. In situ hybridization was done with biotin-labeled antisense synthetic oligonucleotide probes. About 80% or more of the pyramidal neurons in the hippocampal subregions expressed mRNAs for individual receptors in the brains of subjects younger than 65. The ratio of mRNA-containing neuron density to total neuron density significantly decreased with age for GR in CA1 and CA3, and for AR in CA1. Non-significant trends in the reduction with age in the ratio of ER mRNA-containing neurons in CA1 and the ratio of GR mRNA-containing neurons in the hilus also were found. Age-related reductions in nuclear receptor protein mRNA expression in neurons in the hippocampal subfields may be important in the impairments of cognition, emotion, and responses to acute stress in the aged.

Adult↗

Heat-shock cognate 70 messenger RNA expression in postmortem human hippocampus: regional differences and age-related changes.

In situ hybridization of postmortem human brain tissue showed that constitutive heat-shock cognate 70 (hsc 70) mRNA was expressed in more than 50% of the pyramidal neurons in the hippocampal subfields. The ratio (%) of the hsc 70 mRNA-expressing neurons to the total neurons was significantly greater in CA3 and the hilus than in CA1 and CA2. The lower ratio in CA1 may be related to its vulnerability to various stresses. The ratio of hsc 70 mRNA-expressing neurons in CA1 was significantly greater in the older subjects than in the younger ones. This may reflect the up-regulated hsc 70 mRNA induction in response to a reduction in free hsc 70 because the binding of hsc 70 to aberrant proteins may be increased in aged persons.

Adult↗

Effects of doxorubicin on cancer cells after two-thirds hepatectomy in rats.

A rat model of liver metastases generated by intraportal injection of syngeneic tumor cells after two-thirds hepatectomy was used to determine the optimal regional chemotherapeutic modality for early hepatic metastases. WKA rats had viable tumor cells injected directly into the portal vein after two-thirds hepatectomy. Ten rats were used as a control; the remaining groups were given doxorubicin (4/3 mg/kg) injected directly into the hepatic artery at 24 hr, 72 hr, and 7 days (after liver regeneration) postoperatively. The mean survival period in each group was 21.0, 20.0, 20.5, and 20.7 days, respectively, compared with those treated with doxorubicin (4 mg/kg) injection at 24 hr, 72 hr, and 7 days postoperatively, with a mean survival period in each group of 20.0, 21.6, and 25.6 days, respectively. When a comparison was made with regard to the doses of doxorubicin administered, statistically significant differences in survival rates were recognized between the rats that had doxorubicin (4 mg/kg) injection 7 days postoperatively and the others (P < 0.01). Based on these findings, we believe that appropriate adjuvant chemotherapy should be given after the liver regeneration phase.

Animals↗

Lamina-specific cues guide outgrowth and arborization of retinal axons in the optic tectum.

In the chick, retinal axons enter the optic tectum through a superficial lamina, then branch into distinct deeper retinorecipient laminae, where they arborize and form synapses. To study factors that guide this laminar selectivity, we devised an organotypic culture system in which a transverse tectal section is overlaid with a retinal explant large enough to allow unimpeded access to all tectal laminae. Outgrowth, branching, and arborization patterns of retinal axons on tectal slices were lamina-selective, indicating the existence of localized cues that guide retinal axons. Further studies suggested that some of these cues are: (1) associated with cell membranes or extracellular matrix (because axons grew selectively on chemically fixed tectal sections); (2) intrinsic to the tectum (because axons grew selectively on tectal sections prepared from enucleated embryos); (3) distinct from topographic cues (because axons from nasal and temporal retina behaved similarly on anterior tectal slices); and (4) selective for retinal axons (because axons growing from other explants exhibited different laminar preferences).

Animals↗

Target-independent diversification and target-specific projection of chemically defined retinal ganglion cell subsets.

In diverse vertebrate species, defined subsets of retinal ganglion cells (RGCs, the neurons that project from retina to brain) are distinguishable on the basis of their dendritic morphology, physiological properties, neurotransmitter content and synaptic targets. Little is known about when this diversity arises, whether diversification requires target-derived signals, and how subtype-specific projection patterns are established. Here, we have used markers for two chemically defined RGC subsets in chick retina to address these issues. Antibodies to substance P (SP) and the nicotine acetylcholine receptor (AChR) beta 2 subunit label two small ( < 10%), mutually exclusive groups of RGCs in mature retina. SP and AChRs accumulate in distinct RGCs before retinotectal synapses have formed. Moreover, both populations of RGCs form in retinae that develop following tectal ablation or transplantation to the coelomic cavity. Thus, RGC subsets acquire distinct neurotransmitter phenotypes in the absence of extraretinal cues. In the mature optic tectum, SP- and AChR-positive RGC axonal arbors are confined to distinct retinorecipient (synaptic) laminae. In the developing tectum, SP- and AChR-positive axons are initially intermingled in a superficial fiber layer, but then enter and arborize in appropriate laminae soon after those laminae form. Importantly, SP-positive axons, which synapse in a superficial lamina, never extend into the deeper, AChR-positive lamina. Tectal interneurons rich in SP receptors are concentrated in the lamina to which SP-positive RGC axons project, and a set of cholinergic (choline acetyltransferase-positive) tectal projection neurons elaborate dendrites in the lamina to which AChR-positive RGC axons project. These populations of tectal neurons, which are likely targets of the RGC subsets, form in tecta that develop following enucleation. Thus, RGCs and their targets can diversify in each others absence. Accordingly, we propose that the lamina-selective connectivity we observe reflects the presence of complementary cues on RGC subsets and their laminar targets.

Animals↗

[Fas antigen gene in thymuses from patients with myasthenia gravis].

The Fas antigen is a cell surface protein that can mediate apoptosis, and plays a major role in functional maturity in clonal deletion of autoreactive T cells in the thymus. Recently a cDNA encoding the human Fas antigen was isolated. It was suggested that a signal-transducing domain, along with inhibitory one, was presented in the cytoplasmic domain of the Fas antigen. We examined whether any abnormality in Fas antigen gene may breakdown the immunotolerance in patients with myasthenia gravis (MG). We used single-strand conformational polymorphism (SSCP) analysis, generally used to screen for unknown mutation, to examine the cytoplasmic cDNA of Fas antigen obtained by reverse transcription (rt)-PCR from mRNA of MG thymuses. Furthermore, we studied in situ expression of Fas antigen mRNA in thymuses from MG patients. Fragments from all the 12 (3 control subjects, and 9 MG patients) thymuses produced by rt-PCR showed equally stained two bands of the two single strands. In the thymuses from both controls and MG patients, the Fas antigen mRNA was mainly expressed in small thymic cells. These cells were located near clustered cells with relatively large cytoplasms in the cortex and sometimes surrounded them, but were also founded in clusters in the follicules. In situ expressions of Fas antigen mRNA were more remarkable in MG thymuses than in control subjects, and in hyperplastic thymuses than in normoplastic ones. These results suggest that mRNA for the cytoplasmic domain of the Fas antigen have no mutation, and its expression is not reduced in thymuses from patients with MG.

Adolescent↗