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Biomedical subjects

K Yoshimura

Publications and source records attributed to K Yoshimura.

At least 127 records · Page 7Linked to original sources

Pulmonary vascular distensibility of arterial, middle, and venous regions in newborn lambs.

The pulmonary circulation in the adult is characterized by being relatively distensible, but whether the newborn lung shares this feature is less certain. We perfused isolated lungs treated with indomethacin from lambs of four ages (less than 1, 2-4, 12-14, and 30-32 days) to determine the effects of increasing left atrial pressure on the pulmonary vascular pressures measured by vascular inflow and outflow occlusion. An index of pulmonary vascular distensibility was assessed by comparing the slope of the pulmonary vascular pressure at the upstream end of a region as a function of the pressure at the downstream end of the region. A vascular distensibility index (VDI) of 1 indicates a rigid nondistensible system, whereas a VDI less than 1 indicates some degree of distensibility. During normoxia, lungs from all age groups were relatively indistensible as determined by VDI for the total vasculature (VDItotal) as well as for the different regions based on occlusion pressures (VDIarterial, VDImiddle, and VDIvenous). There were significant effects of age on the VDItotal, with decreases in the normoxic values occurring over the first 12-14 days of age, indicating an increase in pulmonary vascular distensibility. Only the VDIvenous was similarly affected by increasing neonatal age. Hypoxia significantly reduced the VDItotal in these same age groups. In addition, hypoxia, which increased the pressure gradients of the arterial and middle regions, significantly increased the VDIarterial in the youngest and oldest age groups but significantly decreased the VDImiddle at all ages by approximately 50%. In summary, we observed age-related changes in the vascular distensibility of the pulmonary circulation, with the VDItotal decreasing with increasing postnatal age.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Expression of the secretory leukoprotease inhibitor gene in epithelial cells.

The secretory leukoprotease inhibitor (SLPI) gene codes for a 12-kD protein that within the lung protects the airway epithelium from neutrophil elastase. Screening of 228 alleles in 114 individuals for sequence differences by RNase protection of genomic DNA revealed no detectable polymorphisms in SLPI gene exons II-IV. SLPI gene expression in the lung was demonstrated by identifying SLPI mRNA transcripts in bronchial epithelial cells freshly isolated from normals. Cell lines derived from mucosal surfaces (HS-24 bronchial squamous cell carcinoma, HeLa cervical carcinoma) actively transcribe the SLPI gene and contain SLPI mRNA transcripts, while lung fibroblasts demonstrate no evidence of SLPI gene expression. SLPI mRNA transcripts appear to be relatively stable, with mRNA levels only mildly affected by inhibition of RNA synthesis. Chromatin DNA of HS-24 cells demonstrates two DNase I hypersensitivity sites within the 5' flanking region of exon I of the SLPI gene, whereas fibroblast chromatin has no DNase I accessible sites in the same region. Further analysis of the 5' flanking region demonstrated two contiguous transcription start sites, CAAT and TATA boxes, and several potential regions of known DNA binding proteins. Overall, the SLPI gene appears to be a relatively nonpolymorphic, stable gene that is constitutively expressed at specific tissue sites, but has the potential to be modulated at both the transcriptional and posttranscriptional levels.

Base Sequence

Indomethacin prevents ventilation-induced decreases in pulmonary vascular resistance of the middle region in fetal lambs.

Previously, we report that the major site of pulmonary vascular resistance in fetal lambs occurred in the middle region defined by vascular occlusion, and that this region exhibited the greatest decrease upon ventilation with O2. To assess the relative individual contributions of ventilation and oxygenation to this decrease, we determined the distribution of pressures across the pulmonary circulation in isolated perfused lungs from 20 fetal lambs (131 - 137 d gestation) by inflow and outflow vascular occlusions. A membrane oxygenator was included in the extracorporeal circuit to control the PO2 at 4 kPa (30 torr) in the unventilated fetal lungs. Half of the fetal lungs were ventilated first without changing the initial gas tensions, and the others were oxygenated first by changing the initial gas tension to a hyperoxic mixture [PO2 = 26.6 kPa (200 torr)] without ventilation. Finally, both groups of lungs were ventilated and oxygenated. In addition, indomethacin was added to the perfusate (0.112 mM, or 40 micrograms/mL) in half of the preparations in each group to determine the effect of prostaglandins on the distribution of pressures during these conditions. The decrease in the total pulmonary vascular resistance with ventilation and/or oxygenation was primarily due to changes in the middle pressure gradient (delta Pm). In fetal lungs without indomethacin, ventilation without oxygenation reduced delta Pm from 6.1 +/- 0.8 to 2.5 +/- 1.0 kPa, or 74% of the total ventilation- and oxygenation-induced decrease in delta Pm (final value = 1.2 +/- 0.6 kPa).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Evidence for an inequality in the forces that generate principal and reverse bends in sperm flagella.

The response of the mechanism initiating flagellar bends to imposed mechanical transients has been studied by holding the head of a sea urchin sperm in the tip of a sinusoidally vibrating micropipet and then displacing the micropipet laterally at a speed of up to 1.15 micron ms-1 for 1.5 beat cycle, without vibration, before resuming sinusoidal vibration with the initial phase, frequency and amplitude at the new location of the pipet. This transient displacement of the micropipet delays the initiation of the bend that was due to initiate 0.5 beat cycle after onset of the displacement. The amount of this delay increases with the speed of the displacement, for speeds up to 1 micron ms-1. Analysis of the flagellar waveforms during the transient showed that with imposed displacements at speeds of equal magnitude, the initiation of a principal bend was delayed to a longer extent than that of a reverse bend. At a micropipet speed of 0.75 micron ms-1, there was an average delay of 0.21 beat cycle in the initiation time of a principal bend as compared to a delay of only about 0.04 beat cycle in the initiation time of a reverse bend during displacements in the opposite direction. For both principal and reverse bends, the second bend due to initiate during the transient displacement initiated in most of the cases with no delay, regardless of the micropipet speed. Our results suggest that the force generated by microtubule sliding to initiated a new reverse bend is greater than that generated to initiate a principal bend.

Animals

Dynamic changes in the rate of amylase release induced by various secretagogues examined in isolated rat parotid cells by using column perifusion.

Isolated parotid acinar cells were perifused in small columns by embedding them in Bio-Gel P-2 beads as an inert supporting matrix, and the effect of carbamylcholine, substance P, and isoproterenol on the rate of amylase release was examined by measuring amylase activity in the effluent. Amylase release by continuous stimulation with carbamylcholine and substance P was biphasic. They caused a rapid and large increase in the rate of amylase release that reached maximum 30 to 60s after the onset of stimulation, followed by a rapid decline to a lower sustained level that was maintained as long as the agonists were present. The rapid decline in the rate of amylase release was due to rapid development of refractoriness. Repeated 1 min pulse stimulation with these secretagogues showed that recovery from refractoriness was also rapid in onset, and 1 min of washout was sufficient to cause significant recovery from refractoriness for both carbamylcholine and substance P. Recovery, however, was not complete after 10 min of washout. Amylase release by continuous stimulation with isoproterenol, on the other hand, developed more slowly with the peak rate being attained at about 6 min after the onset of stimulation. Refractoriness was not observed in the effect of isoproterenol. The maximum effect in the rate of amylase release attained by carbamylcholine or substance P was higher than that by isoproterenol. These results suggest that the apparent small effect of carbamylcholine and substance P on amylase release reported earlier by using batch systems is probably due to the rapid development of refractoriness to these secretagogues, but not to isoproterenol.

Amylases

[A case of pituitary adenoma and hyperplasia with primary hypothyroidism].

A 23 year-old woman was admitted to our hospital, complaining of sterility and obesity. Her serum TSH and Prolactin were abnormally high, and her serum T3, T4 were low. Contrast-enhanced computerized tomographic (CT) scan revealed a round mass in the sella and suprasellar region. A transsphenoidal operation was then performed. The intrasellar mass was composed of a soft liquid-like part and a solid part. Only the soft liquid-like part of the mass was removed. Histological examination showed the typical appearance of chromophobe adenoma, Reticulin stain of the specimen revealed no reticular network. The remnant of the mass was considered to be hyperplasia because the size of the mass decreased on serial CT scan after thyroid hormonal replacement. Sometimes it may be difficult to distinguish between hyperplasia and adenoma. The application of reticulin stains is considered to be useful for differentiation between hyperplasia and adenoma.

Adenoma

[The fate of patients with intermittent claudication--comparison of surgical and non-surgical treatment].

The purpose of this study was to determine the operative indication for patients with intermittent claudication because of arteriosclerosis obliterans, and to compare the late result of the surgical treatment group (130 cases, 175 limbs) with that of the non-surgical treatment group (27 cases, 31 limbs). There were 3 operative deaths and 21 late deaths in the surgical group, and 11 late deaths in the non-surgical group. The number one cause of death was heart failure, including ischemic heart disease, in both groups. The 5-year cumulative patency rate was 92.5% in the aorto-iliac, 70.6% in the femoro-distal and 82.0% in the aorto-femoro-distal arterial reconstructions. Long term symptom free rates of the surgical group and the non-surgical group, except fatal cases, were 87.2% and 25.0% in the aorto-iliac, 57.7% and 25.0% in the femoro-distal, 86.7% and 0% in the aorto-femoro-distal arterial regions, respectively. Late result of intermittent claudication in the surgical group was better than that in the non-surgical group. We conclude that intermittent claudication should be considered to be the indication for surgery, except for the cases with high risk diseases or malignant diseases.

Female

[Long term follow-up on retinopathy of prematurity treated with photocoagulation--influence of photocoagulation on the eyeball].

The ocular findings in 127 eyes of 69 cases (average 11.6 +/- 3.7 years old) with retinopathy of prematurity (ROP) and treated with xenon photocoagulation between 1970 to 1983 were studied. Chorioretinal changes observed after the photocoagulation therapy revealed that photocoagulation spots gradually transformed from round to long oval forms in the sagittal direction. The photocoagulated lesions became extremely atrophic and larger after several years. In addition, band-shaped retinochoroidal atrophies were found adjacent to photocoagulation spots in 10 eyes (7.9%). Furthermore, vascular anastomoses between retinal and choroidal vessels were demonstrated at scars after treatment by fluorescein angiography. Anastomoses between retinal arteries and choroidal vessels were found in 18 eyes among 71 eyes (25.4%), and anastomoses between retinal veins and choroidal vessels were present in 50 eyes among the 71 eyes (70.4%). These changes may be the result of xenon photocoagulation on the developing premature retina and choroid. However, visual acuities were 0.7 or better in 111 eyes (87.4%). Refractions at the aged six years old were between - 3 to +2.75 diopters in the 94 eyes (83.9%) among the 112 eyes.

Adolescent

[The relationship between ventilatory lung motion and pulmonary perfusion shown by ventilatory lung motion imaging].

Using ventilatory lung motion imaging, which was obtained from two perfusion lung scintigrams with 99mTc-macroaggregated albumin taken in maximal inspiration and maximal expiration, the lung motion [E-I)/I) of the each unilateral lung was studied in various cardiopulmonary diseases. The sum of (E-I)/I(+) of the unilateral lung showed a decrease in the diseased lung of localized pleuropulmonary diseases, including primary lung cancer and pleural thickening, and in both lungs in cases of heart diseases, diffuse pulmonary diseases including diffuse interstitial pneumonia and diffuse panbronchiolitis. The sum of (E-I)/I(+) of the both lungs, which correlated with vital capacity and PaO2, showed a decrease in diffuse interstitial pneumonia, pulmonary emphysema, diffuse panbronchiolitis, primary lung cancer, pleural diseases and so on. (E-I)/I(+), correlated with pulmonary perfusion (n = 49, r = 0.51, p less than 0.001), but not a few cases showed mismatch, which was observed in primary lung cancer, pleural diseases, pulmonary emphysema, diffuse panbronchiolitis and so on. (E-I)/I(+) better correlated with pulmonary ventilation by ventilation scintigraphy with 81mKr or 133Xe (n = 49, r = 0.61, p less than 0.001) than pulmonary perfusion. The ventilatory lung motion imaging, which demonstrates the motion of the intra-pulmonary areas and lung edges, appears useful for estimating pulmonary ventilation of the perfused area as well as pulmonary perfusion.

Heart Diseases

Production, purification and characterization of biologically active recombinant human nerve growth factor.

The human NGF gene was isolated and inserted downstream from murine leukemia virus LTR in a plasmid having dihydrofolate reductase cDNA. The expression plasmid was introduced into CHO cells. Selection of the transformants for the resistance to methotrexate gave a CHO cell line which produced human NGF at a level of 4 mg/L in the culture medium. The recombinant human NGF was purified to near homogeneity from the culture supernatant. The NH2-terminal amino acid sequence, the COOH-terminal amino acid (Ala), and the amino acid composition of the human NGF were identical to those deduced from the nucleotide sequence of the human NGF gene. The recombinant human NGF was composed of 120 amino acid residues. Three disulfide linkages were determined to be Cys15-Cys80, Cys-58-Cys108, and Cys68-Cys110; the locations were identical to those in the mouse 2.5S NGF molecule. The specific biological activity of the recombinant human NGF was comparable with that of authentic mouse 2.5S NGF as determined by stimulation of neurite outgrowth from PC12 cells.

Amino Acid Sequence

Cloning and expression of a cDNA encoding a novel human neurotrophic factor.

A cDNA encoding a novel human neurotrophic factor (designated nerve growth factor-2; NGF-2) was cloned from a human glioma cDNA library using a synthetic DNA corresponding to human nerve growth factor (NGF). The cloned cDNA encodes a polypeptide composed of 257 amino acid residues including a prepro-sequence of 138 residues and a mature region of 119 residues. The amino acid sequence of human NGF-2 exhibits 58% similarity with that of human NGF. Conditioned medium of COS-7 cells transfected with an expression plasmid for human NGF-2 cDNA supported the survival of sensory neurons isolated from dorsal root ganglia of embryonic chicks. A 1.5 kb of NGF-2 mRNA can be detected from an early development stage in rat brain, by Northern blotting analysis.

Amino Acid Sequence

A monoclonal antibody 5E5 recognizes an intranuclear antigen selectively present in a subpopulation of the neurons.

Monoclonal antibody 5E5 labeled the nuclear antigen of the neurons in the guinea pig and rat central nervous systems including the cerebrum, cerebellum, spinal cord and retina. This antibody could discriminate neurons even among the same cell class. In in vitro study, only 10% of dividing PC12 cells was labeled with this antibody. An electron microscopic immunohistochemical study also revealed that this antibody selectively labeled heterochromatins in the neurons. Although we could not obtain any positive result by an immunoblot study, the antigenicity was remarkably diminished by the DNase I or S1 nuclease treatment on the tissue sections whereas RNase and trypsin was ineffective. These results suggested that this antigen might be a single-stranded DNA-protein complex resistant to proteolytic procedures, and possibly related to cell function or state of differentiation.

Animals

Alteration in density of eosinophils in the cerebrospinal fluid of mice infected with Angiostrongylus cantonensis.

The density of eosinophils in the cerebrospinal fluid (CSF) and blood of male ddY mice infected with Angiostrongylus cantonensis was examined on days 14, 20 and 27 post-infection (p.i.) with discontinuous Percoll gradient centrifugation. Normal blood eosinophils had a density of between 1.070 and 1.080 g ml-1. No significant changes in density in blood eosinophils were noted during the course of the observations. CSF eosinophils began to become hypodense (defined as density less than 1.070 g ml-1) on day 20 p.i., and 88% of eosinophils were hypodense on day 27. Our results suggest therefore that eosinophils probably become hypodense in the CSF and brain tissues, but not in the blood.

Angiostrongylus

Solitary neurofibroma of scrotum.

We report a case of solitary neurofibroma of the scrotum. These tumors, which arise from perineural and Schwann cells, commonly occur throughout the body but they rarely have been reported to originate in the scrotum. No stigmata of von Recklinghausen's disease were identified.

Adult

Differences in responses of rat- and guinea-pig-eosinophils to eosinophil chemotactic factors derived from Angiostrongylus cantonensis.

Eosinophil chemotactic activity associated with whole worm extracts of the young adult worms (YA) and 1st stage larvae (L1) of Angiostrongylus cantonensis was assessed using guinea-pig- and rat-eosinophils. Both whole worm extracts were potently chemotactic to guinea-pig-eosinophils whereas only the whole worm extract of L1 was chemotactic to rat-eosinophils. Gel filtration chromatography of YA-whole worm extract yielded an eosinophil chemotactic factor (ECF-YA) with an estimated molecular weight of 16,900. ECF-YA was resistant to heating and pronase digestion but sensitive to periodate oxidation, suggesting that chemotactic activity was possibly associated with the sugar portion of the glycoprotein molecule. Guinea-pig- and rat-eosinophils were deactivated by previous incubation with homologous whole worm extracts but not with heterologous ones. When guinea-pig-eosinophils were treated with trypsin or pronase, their chemotaxis to ECF-YA was significantly inhibited, and pronase treatment was more effective. Both deactivated and trypsin-treated guinea-pig-eosinophils completely recovered their chemotaxis responses after in vitro culture for 12 and 24 h, respectively. When those eosinophils were cultured in vitro in the presence of puromycin or cycloheximide, however, their chemotaxis responses could not be recovered. These data clearly indicate that guinea-pig-eosinophils probably possess a kind of receptor (or 'recognition unit') capable of reacting to ECF-YA, and also that the receptor may be protein or glycoprotein molecules, and reproducible.

Angiostrongylus

Neonatal tuberous sclerosis with heart and brain tumors.

A 6-day-old neonate with tuberous sclerosis having brain and cardiac tumors is reported. The patient presented with a seizure 20 minutes after birth. Cranial ultrasonography and computed tomography on admission showed a large and round high-density tumor lesion in the left frontal lobe. Echocardiography also showed a large tumor lesion beside the left ventricle wall, and a diagnosis of tuberous sclerosis was promptly made. Two months later, a periventricular calcified lesion was found on the demonstrated portion, and the tumor lesion initially observed in the brain had disappeared. These findings suggest that the initial tumor lesion found in the brain developed into a typical calcified lesion.

Brain Neoplasms

Hyperammonemia in multiple myeloma.

Two patients with multiple myeloma who appeared to be producing ammonia are reported. Both patients showed hyperammonemia and amino acid disturbances, such as a low Fischer ratio. One patient had Bence Jones protein (lambda) type myeloma and became comatose, but the hyperammonemia and disturbance of consciousness were improved by chemotherapy for the myeloma. The other patient had IgA kappa type myeloma and somnolence and died of malignant pleurisy despite intensive chemotherapy. Autopsy showed widespread multiple myeloma and an almost normal liver. Ammonia levels in the supernatant of cultured myeloma cells from the patient's pleural effusion increased almost linearly from the time of cell seeding. These observations showed that ammonia was produced at a high level by these human myeloma cells. We also found that one of the common myeloma cell lines, RPMI 8226, could produce ammonia as well.

Amino Acids