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Biomedical subjects

K Shima

Publications and source records attributed to K Shima.

At least 19 recordsLinked to original sources

High-performance affinity chromatography system for the rapid, efficient assay of glycated albumin.

A high-performance affinity chromatographic system was constructed and shown to permit highly reproducible, rapid, automatic assays of serum glycated albumin (GA) by separation of albumin (Alb) on an anion-exchange column (Asahipak ES-502N) packed with a vinyl alcohol copolymer bearing diethylamino groups and consecutive separation of GA on a column packed with a vinyl alcohol copolymer bearing boronate groups. The first column selectively retained Alb free of other serum proteins and permitted at least a 95% recovery of sample Alb. The purity of the Alb peak was confirmed by two-dimensional electrophoresis. Chromatographic analyses of human serum Alb incubated with glucose on the second column showed that the peak area for GA increased in accordance with the incubation time and suggested selective adsorption of GA on the second column. Optimization of the conditions for the two-column system reduced the analysis time to 10 min. Analyses of human sera with the present system showed GA to be 16.1 +/- 1.1% (mean +/- S.D.) of total Alb in non-diabetic children and 39.9 +/- 9.1% (mean +/- S.D.) in diabetic children (0-17 years old).

Adolescent

Correlation between residual beta-cell function and age at onset of spontaneous diabetes in Long Evans Tokushima lean rats.

We studied the natural course of disease in spontaneously diabetic rats, Long Evans Tokushima Lean (LETL) rats, to determine whether it showed similar pathogenetic heterogeneity to that of patients with insulin-dependent diabetes mellitus (IDDM) with regard to the relationships between age at onset, rapidity of disease progress, and degree of beta-cell function at the time of its manifestation. Type 1 diabetes developed in 35 rats (6.3%) between 40 and 140 days of age. Eight rats that became diabetic at age 69 days or less were more severely ketotic at the time of first detection of glycosuria and showed more rapid deterioration than seven rats that became diabetic later after birth (mean plasma 3-hydroxybutyrate levels, 4,707 +/- 1,215 pmol/L v 1,390 +/- 859 pmol/L; mean +/- SEM, P < .01). The mean plasma levels and pancreatic content of immunoreactive insulin (IRI) of the early onset rats, 47 +/- 13 pmol/L and 19 +/- 12 pmol/g tissue weight, were significantly lower (P < .01) than the corresponding values of the late-onset rats, 262 +/- 52 pmol/L and 348 +/- 87 pmol/g tissue weight, respectively. Both values were markedly lower than the mean values of 25 nondiabetic LETL rats, 976 +/- 122 pmol/L and 3,488 +/- 628 pmol/g tissue weight. Plasma immunoreactive glucagon (IRG) levels were significantly increased in the diabetic groups (early onset, 57 +/- 13 pmol/L; late-onset, 51 +/- 12 pmol/L; nondiabetic, 18 +/- 1 pmol/L; P < .01). These changes in pancreatic hormone levels of the early onset and late-onset rats were compatible with the histological features of their pancreatic islets.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Decrease in plasma GLP-1 immunoreactivity in starved rats.

To determine whether starvation affects the metabolism of glucagon-like peptide-1 (GLP-1), we measured the plasma levels of proglucagon-derived peptides and the biosynthesis and posttranslational processing of proglucagon in groups of six rats starved for 1, 3 and 5 days. The plasma levels of GLP-1 immunoreactivity (GLP-1 IR) and glucagon-like immunoreactivity (GLI) decreased during starvation reaching 79 and 56% of the respective control values by day 5 (P less than 0.05 and less than 0.01 vs control). The same is true of the plasma IRI level. The ileal contents of GLP-1 IR and GLI were 50.8 +/- 3.8 pmol/g wet weight and 161.8 +/- 13.2 pmol/g wet weight, respectively, on day 5 of starvation, which were significantly lower (P less than 0.01) than the respective values of 94.8 +/- 16.6 pmol/g wet weight and 262.7 +/- 28.1 pmol/g wet weight in control rats. However, the pancreatic contents of proglucagon-derived peptides tended to increase during starvation, although their increases were not statistically significant. No significant change in the posttranslational processing of proglucagon was detected during starvation. The decrease in the ileal proglucagon-derived peptides content was not associated with a decrease in intestinal proglucagon mRNA transcripts. These results suggested that decreased synthesis of proglucagon-derived peptides by the intestine was largely responsible for the reductions in their circulating levels in starved rats.

Analysis of Variance

The response of glycated albumin to blood glucose change in the circulation in streptozotocin-diabetic rats--comparison of theoretical values with experimental data.

The contribution of the preceding blood glucose level to glycated protein was theoretically analyzed using a linear kinetic model and was compared with experiments using streptozotocin-diabetic rats. We assumed that the glycation process can be described by one irreversible step and that the fraction of glycated protein is small. A formula based on these two assumptions showed that the level of glycated protein was proportional to the weighted mean blood glucose concentration in the preceding period and that the weight function was determined by the metabolic characteristics of each protein. For assessing the usefulness of the present formula, the value calculated for the response of glycated albumin (GA) to acute blood glucose change in streptozotocin-diabetic rats was compared with the data obtained under three experimental conditions. The calculated responses of GA showed a little more retardation than the observed data, but showed enough agreement with them.

Animals

Epidermal growth factor binding sites in porcine granulosa cells and their regulation by follicle-stimulating hormone.

Epidermal growth factor (EGF) modulates ovarian function, including folliculogenesis and steroidogenesis. We investigated the localization of EGF binding sites in the porcine ovary, and the effect of FSH on EGF binding to cultured granulosa cells. Autoradiographic study demonstrated that the binding sites for 125I-labeled mouse EGF in the porcine ovary were present in the granulosa and luteal cells, but not in the thecal cells. Porcine granulosa cells were collected by the needle aspiration method from small (1-2 mm) and medium-sized (3-5 mm) follicles. Scatchard analysis showed that a single class of the specific binding sites for EGF was present in the granulosa cells. The number of binding sites and the apparent dissociation constant were 5,540 binding sites/cell and 0.23 nM (medium-sized follicle), respectively. No significant difference was observed between small and medium-sized follicles. Granulosa cells were cultured for 48 h at 37 degrees C in medium alone or with increasing doses of ovine FSH (1-100 ng/ml). FSH treatment significantly increased EGF binding in a dose-dependent manner. In conclusion, it is suggested that the specific high affinity, low capacity binding sites for EGF are present in porcine granulosa cells, and that they are up-regulated by FSH.

Animals

The fate of calvarias implanted into the epidural spaces of rats. A preliminary study.

The histologic changes occurring in newborn rat calvarias implanted into the epidural space of adult rats were observed to determine whether this method was adequate as an experimental model of new bone formation in the spinal canal. Two weeks after implantation, all implanted calvarias of newborn rats grew with ossification in the epidural space. The grafted calvarias continued to grow gradually 6 weeks after this procedure. Six months later, 40% of the grafted calvarias showed progressive bone formation with osteoblasts, chondrocytes, and immature mesenchymal cells. In the other 60%, the implanted calvarias had developed into mature trabecular bone. Twelve months after the procedure, the calvarias had developed into mature bone in all cases, although the size of the grafted calvarias tended to decrease in size. It was concluded that this experiment had devised a suitable model for understanding the process of new bone formation in the spinal canal.

Animals

Hypertrophied ligamentum flavum in lumbar spinal canal stenosis. Pathogenesis and morphologic and immunohistochemical observation.

To investigate the pathogenesis of hypertrophy of the ligamentum flavum, 45 cases of lumbar canal stenosis were evaluated by computed tomography scan and pathologic and immunohistochemical studies. The ligamentum flavum along with the medial one-third of the superior facet was obtained en bloc to include the enthesis. Statistically significant differences in transverse area and thickness of the ligamentum flavum were evident compared to the control group (P < 0.01). Pathogenesis of the hypertrophied ligamentum flavum was classified into three major groups: 1) fibrocartilage change due to proliferation of type II collagen, 2) ossification, and 3) calcium crystal deposition. It is stressed that marked proliferation of Type II collagen from the enthesis to the ligament side was revealed in the capsular portion of the hypertrophied ligament.

Adult

Gonadotropin receptors in human ovarian follicles and corpora lutea throughout the menstrual cycle.

To study changes in the binding of gonadotropins to human follicles and corpora lutea, we have examined the binding of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the human ovary throughout the menstrual cycle, by both quantitative binding assays and surface binding autoradiography. The specific high-affinity low-capacity receptors for hLH were demonstrated in both human follicles and corpora lutea. Binding of 125I-hFSH was identified in the granulosa cells, but not in the thecal cells of the preantral and antral follicles at various stages of follicular development. The binding of 125I-hLH to the thecal cells increased during follicular development, and a dramatic increase was preferentially observed in the granulosa cells of the preovulatory follicles. In the corpora lutea, the binding of 125I-hLH increased from the early luteal phase to the midluteal phase and decreased towards the late luteal phase. The results of the present study suggest that changes in the binding of gonadotropins in the ovarian target cells during the menstrual cycle might play an important role in the regulation of follicular and luteal function.

Autoradiography

Analysis by the polymerase chain reaction of histocompatibility leucocyte antigen-DR9-linked susceptibility to insulin-dependent diabetes mellitus.

DNA sequence analysis of class II HLA from Caucasian and black patients with type 1 (insulin-dependent) diabetes mellitus has suggested that aspartic acid at position 57 (Asp 57) of the DQ beta chain provides protection against insulin-dependent diabetes mellitus (IDDM). In contrast, most Japanese patients with IDDM have Asp 57-positive alleles. To determine the reason for the differences and to localize the HLA-linked diabetogenic gene in Japanese, we studied the DQA1 and DQB1 genes of Japanese patients with IDDM and control subjects by the polymerase chain reaction in combination with restriction fragment length polymorphism analysis. Associations of DQA1*0301 and DQB1*0303 with IDDM were observed. DQA1*01 was associated negatively with IDDM. The HLA-DR9 haplotype, which is associated positively with IDDM in Japanese, was associated with DQA1*0301 and DQB1*0303, indicating that the Japanese DR9 haplotype is the same as that in caucasians but different from that in blacks. Of the loci on Japanese DR9 haplotypes, the DQA1*0301 allele showed the highest association with IDDM. DQB1*0303 was also positively associated with IDDM. Since DQB1*0303 is identical to DQB1*0302 except that it contains Asp 57, the data suggests that an Asp 57-positive allele confers susceptibility to IDDM when the whole molecule of the DQ beta chain is similar to other susceptible DQ beta chains. DQA1*0301 appears to be a marker of IDDM in all these populations: Japanese, caucasian, and black.

Adult

Multiple sclerosis in Hokkaido, the northernmost island of Japan: prospective analyses of clinical features.

We analyzed the clinical features of multiple sclerosis (MS) prospectively seen between July 1986 and October 1989 on Hokkaido island, the northernmost part of Japan. Clinical features were generally considered to be intermediate between the previous Japanese reports and those of Western countries. Devic's disease was rare and simultaneous bilateral visual loss at on set was not too common this series, differing from that previously reported of Japanese MS. The high incidence of acute transverse myelopathy and lesser involvement of the cerebellum, however, support the previous view. Further clinical and epidemiological studies will be necessary on this island.

Adult

The effect of hypoxia on brain edema--the promoting effect of superimposed hypercapnia or hypertension.

The effects of hypoxia and superimposed hypercapnia or hypertension during hypoxia on brain tissue water content, pH, and electric activity were studied in Sprague-Dawley and stroke-prone spontaneously hypertensive rats. Auditory brainstem responses and sensory evoked potentials were recorded during the experiment as the indices for cerebral oxygen metabolism. The brains were removed immediately, 1 day, and 2 days after hypoxic insult for gravimetric study. The brain water content increased in all groups on the 1st and 2nd days after hypoxia. The percentage change from the control water content increased only on the 1st day in hypoxic rats. In contrast, it increased on both the 1st and 2nd days after hypoxia in hypercapnic or hypertensive rats. The evoked potentials of hypoxic and hypercapnic-hypoxic rats showed that peak latencies were prolonged significantly during hypoxia and recovered 1 and 2 days after hypoxia. The brain tissue pH decreased during hypoxia and recovered after hypoxia. This study suggests that brain edema develops within 2 days of hypoxic insult and that superimposed hypercapnia or hypertension promotes the brain edema.

Animals

[A case of hyperinsulinemia due to hypersecretion of incretin].

A 65-year-old male presented with postprandial hypoglycemic episodes. He had normal glucose tolerance, but plasma glucose reached a hypoglycemic level of 31 mg/dl at 120 min during 75 g oral glucose tolerance test. He had markedly increased insulin response to oral glucose but not to intravenous glucose, intravenous arginine or intravenous glucagon. Hyperresponse of insulin after oral but not intravenous glucose suggested the possible involvement of insulinotropic hormonal factor in the gut (incretin) in hyperinsulinemia of this patient. Therefore we evaluated the secretory response of glucagon like peptide-1 (GLP-1), a most likely candidate for incretin, to oral and intravenous glucose administration. Plasma GLP-1 response to oral glucose was almost five times greater than that of normal subjects. On the other hand, there was no significant response in plasma GLP-1 after intravenous glucose. These results suggest that hypersecretion of GLP-1 may be responsible for the hyperinsulinemia after oral glucose in this patient.

Aged

[Creatine kinase activity and its isozyme levels in cord blood].

We measured creatine kinase (CK) levels of cord blood and evaluated them in relation to the degree of maturity and distress. The reference value of CK of cord blood in normal neonates was 209 +/- 99 U/l (mean +/- SD) and the percent values of the isoenzymes, CK-MM, CK-MB and CK-BB, were 86.7 +/- 6.2%, 5.1 +/- 2.6%, and 8.1 +/- 5.4%, respectively. There was a positive correlation between the birth weight and CK, CK-MM, CK-MB and CK-BB levels of cord blood. The CK and CK-MM levels of cord blood in the neonates who were prematurely delivered and small-for-date were significantly lower than those in normal controls. The CK and CK-MM levels of cord blood in the neonates with low Apgar scores, 6-4 and 3-0, were 172 +/- 74, 145 +/- 73 and 104 +/- 63, 92 +/- 55 U/l, respectively, which were significantly lower than those in the neonates with the high scores (10-7), 208 +/- 104, 183 +/- 92 U/l. The neonates with distress showed the low CK and CK-MM values, 76 +/- 12 and 61 +/- 8 U/l. The CK and CK-MM levels of cord blood tended to decrease with prolongation of labor, but did not differ from each other among the neonates delivered by different modes. These results suggest that the CK and its isoenzyme levels are good indicators for the degree of maturity of neonates and the severity of neonatal distress.

Creatine Kinase

[A case of traumatic spinal subarachnoid hematoma causing compression of the cauda equina].

A case of traumatic spinal subarachnoid hematoma causing compression of the cauda equina is reported here. The patient, a 76 year-old woman, who had fallen down by accident 1 month before, was admitted to our hospital presenting lumbar pain radiating into her right thigh, monoplegia of the right leg and urinary incontinence. Myelography and metrizamide CT demonstrated a filling defect mimicking intradural extramedullary tumor at the level of L1 and L2. Magnetic resonance imagings (MRI) revealed a subacute or chronic hematoma compressing the conus medullaris and the cauda equina. Operation was performed and an old hematoma, which occupied most of the spinal subarachnoid space and compressed the conus and cauda equina from right to left, was removed. No definite bleeding point was detected and no traumatic change was seen on the cord. Neither tumor nor abnormal vessel was detected. After surgery, the symptoms improved partially. On a review of the literature, we found only 4 cases of traumatic spinal subarachnoid hematoma, all of which occupied the cervical or thoracic portion of the spine. Our case is the first report, except for the cases following lumbar spinal tap, of traumatic spinal subarachnoid hematoma causing compression of the cauda equina. Though usually blood in CSF diffuses immediately, a clot may be formed when a large amount of bleeding obstructs the spinal canal. In our case, furthermore, deformity and narrowing of the spinal canal had preceded for many years, following lumbar vertebral compressed fracture related with osteoporosis. This might have promoted the process of canal obstruction and clot formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[The effects of oxygen and vasodilators on pulmonary hemodynamics and blood gases in chronic lung disease].

The effects of oxygen inhalation, nitroglycerin (NTG) and prostaglandin E1 (PGE1) on pulmonary hemodynamics and blood gases were studied in 15 patients with chronic lung disease (CLD). Cardiac catheterization was performed with Swan-Ganz catheter, and pulmonary hemodynamics and cardiac output were measured. After baseline hemodynamics and blood gas measurements were made, 15 patients inhaled oxygen for 15 minutes and the same measurements were repeated. Twenty minutes later, oxygen inhalation was stopped. Then the 15 patients were divided into two groups; one group was administered sublingual NTG (7 patients) and the other was administered PGE1 by continuous intravenous infusion (8 patients). Pulmonary hemodynamics and blood gas measurements were then performed. Oxygen inhalation significantly reduced mean pulmonary artery pressure (from 22.2 +/- 8.8 to 20.0 +/- 6.4 mmHg; p < 0.01) and heart rate (from 78.1 +/- 12.0 to 75.5 +/- 12.5 beats/min; p < 0.05). With respect to oxygenation, oxygen inhalation significantly increased PaO2 (from 68.6 +/- 10.7 to 113.4 +/- 31.4 mmHg; p < 0.01), PvO2 (from 35.1 +/- 3.7 to 38.0 +/- 3.3 mmHg; p < 0.01). Therefore, oxygen inhalation was thought to be useful in patients with chronic lung disease with pulmonary hypertension. Sublingual administration of NTG significantly reduced mean pulmonary artery pressure (from 24.1 +/- 0.2 to 17.6 +/- 6.8 mmHg; p < 0.01), C.I. (from 2.9 +/- 0.2 to 2.3 +/- 0.2 ml/min/m; p < 0.01), O2-transport (from 589.1 +/- 168.4 to 457.0 +/- 105.8 ml/min; p < 0.01), and had a tendency to decrease PvO2 (from 34.3 +/- 3.0 to 32.1 +/- 1.8 mmHg; p < 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Extrapyramidal manifestations in hereditary olivopontocerebellar atrophy--clinical study of 10 cases in three affected pedigrees].

We studied 3 pedigrees affected with autosomal dominant olivopontocerebellar atrophy (OPCA), and clinical features of 10 patients were reported. Clinically, 6 cases were dominated with cerebellar ataxia, one with Parkinsonism, and three with choreiform movements. Furthermore, they were characterized by slow eye movement and progressive loss of tendon reflexes. Generally, extrapyramidal manifestations, such as Parkinsonism or choreiform movements, are occasionally observed in dominant OPCA. However, the pathogeneses are different from each other. The choreiform movements are unique in dominant OPCA, and generally not observed in sporadic OPCA. In the distribution of degenerated foci, dominant OPCA is often associated with degeneration of not only substantia nigra, but also with other structures such as dentate nucleus, red nucleus, external segment of globus pallidus (GPe), and subthalamic nucleus. This dentatorubral and pallido-Luysian system degeneration are parts of neuropathological findings in hereditary DRPLA (Naito-Oyanagi form). In both disorders, choreiform movements is observed. Current theory indicates that hyperactivity of neostriatal dopamine neurons and degeneration of GPe play roles in the pathogenesis of chorea. Clinically, choreiform movements are common in hereditary DRPLA, but not in dominant OPCA. This difference could be explained by the nigral degeneration in dominant OPCA, which suppress the generation of choreiform movements.

Adult

[Pineocytomas; clinicopathological evaluation of 4 cases].

Clinicopathological evaluation of pineocytoma was performed in 4 patients. The subjects, 2 males and 2 females, ranged in age from 17 to 40. All the patients were clinically found to have the symptom of increased intracranial pressure on a monthly basis, but none of them were found to have dorsal midbrain dysfunction symptoms such as Parinaud's sign or Argyll Robertson pupil. Diagnostic imaging produced heterogeneous pictures indicating calcifications and cyst in 2 patients and homogeneous pictures of the tumor parenchyma in the other 2 patients. Histologically, the former cases were found to have many pineal-sand-like calcifications. Median sagittal MR images demonstrated expansive growth of pineocytoma. Quadrigeminal plates which kept their shapes were observed in 2 patients. Craniotomy was performed in all cases, removing the tumor totally in 2 patients. Radiation therapy was given to 3 patients, resulting in complete remission, but radiosensitivity varied according to cases. During the follow-up period of 12 to 42 months, one patient died of peritonitis caused by shunt infection. No recurrence of the tumor was seen in any of the patients. The incidence of pineocytoma was very low. Further evaluation of the tumor involving many cases is advisable.

Adolescent

Freeze-drying and quality evaluation of protein drugs.

Gamma interferon from genetic recombination (IFN) has been found to have an optimal pH at about 7. An increase in IFN concentration may cause a decrease in solution clarity. A proper selection of isotonizing agent, as well as the addition of sugars, is effective in improving the clarity. The amount of IFN adsorbed on filter membranes varies with the membrane materials: cellulose acetate adsorbs much IFN, 2-fluorovinylidene is the next, followed by polysulfon, and polycarbonate adsorbs it least of all materials tested. Stainless steel adsorbs little IFN, and the level can be lowered even more by electropolishing. Silicone coating can decrease the amount adsorbed to about 1 microgram per vial of 10 ml. The effect of pressure given to the IFN solution during filtration is negligible. Transfer of IFN solution through pipings of conventional shape may result in partial deactivation by bubbling. At around pH 7, a lower pH of IFN solution causes a higher moisture level of the freeze-dried product. Moisture levels up to 3% have no effect on IFN stability. Upon reconstitution of freeze-dried IFN by vigorous shaking with distilled water, filtration of the solution may become difficult because polymers might have been formed during vigorous shaking. The addition of L-cysteine, maltose, and human serum albumin, has been found to be as effective in preventing such unfavorable reactions. Fatty acids in human serum albumin, which is effective in stabilizing IFN, has been found to participate in preventing denaturation of human serum albumin upon freezing and freeze-drying; however, the denaturation prevention mechanisms are not clear yet.

Chemistry, Pharmaceutical