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Biomedical subjects

K Ohsawa

Publications and source records attributed to K Ohsawa.

At least 91 records · Page 5Linked to original sources

Cyclosporine A inhibits the secretion of certain anterior pituitary hormones in patients with nephrotic syndrome.

To clarify the effects of cyclosporine A (CsA) on the secretion of serum thyrotropin (TSH), prolactin (PRL), luteinizing hormone (LH) and follicular stimulating hormone (FSH), we performed TRH and LH-RH testing in 4 patients with the nephrotic syndrome before and after the administration of CsA, 6 mg/kg/day for 4 to 12 weeks. Prior to CsA all patients responded normally to TRH with respect to TSH and PRL secretion. Two patients showed normal response of LH and FSH to LH-RH stimulation while the response in 2 other patients, who were both menopausal, was exaggerated. By the third or fourth week of CsA administration the basal and peak TSH and PRL values declined significantly in all patients in response to TRH stimulation while those of LH and FSH showed only a modest decrease in response to LH-RH stimulation. Two to 4 weeks after the cessation of CsA the response of TSH, PRL and FSH returned to the pretreatment level. These observations suggest that: 1) CsA exerts an inhibitory effect on the secretion of at least TSH and PRL in humans, and 2) the effect of CsA on the pituitary may be partially reversible after the cessation of the therapy.

Adult↗

Characterization of the insulin resistance in liver cirrhosis: a comparison with non-insulin dependent diabetes mellitus.

To characterize the mechanisms of insulin resistance in liver cirrhosis (LC), we estimated the peripheral tissue sensitivity and responsiveness to insulin using the euglycemic clamp technique and determined the insulin binding to erythrocytes in patients with compensated LC as well as in patients with non-insulin dependent diabetes mellitus (NIDDM). The insulin dose-response curves of the glucose metabolic clearance rates (MCR) were shifted to the right and downward both in patients with LC and NIDDM, indicating a reduced sensitivity and responsiveness to insulin. In the cirrhotics, MCR at the maximally effective insulin level, an index of insulin responsiveness, was correlated with fasting insulin levels (r = -0.57, P < 0.01) and sigma BG in 75 gOGTT (r = -0.43, P < 0.05), but no correlations were found between them and the diabetics. Although specific insulin bindings to erythrocytes were significantly lower in patients both with LC and NIDDM, Scatchard analysis revealed a significant decrease in the number of insulin receptors in the cirrhotics, and a decrease in the empty-site affinity in the diabetics. These findings suggest that insulin resistance in LC consists of a combination of binding and postbinding defects. The latter defect may be caused by basal hyperinsulinemia and contribute to the development of glucose intolerance. Although binding and postbinding abnormalities are also found in NIDDM, the mechanisms of insulin resistance in LC and NIDDM may be different.

C-Peptide↗

[Morphometric and immunohistochemical studies of the suprachiasmatic nucleus in the hereditary microphthalmic rat].

Morphometric and immunohistochemical analyses of the suprachiasmatic nucleus (SCN) were performed on hereditary microphthalmic rats. In normal rats, the number of cells and the volume of the SCN were 11, 631 and 6.7 x 10(-2) mm3 (an average taken from 12 SCNs). However, the neuronal population and volume of the SCN in hereditary microphthalmic rats were 7,450 and 4.5 x 10(-2) mm3 (an average taken from 14 SCNs), respectively. There were no significant differences in the size of neurons between normal and microphthalmic SCN neurons. Immunohistochemical studies showed that a considerable number of antivasopressin positive neurons were present in microphthalmic rats, despite their lack of the optic nerve. However, further detailed studies revealed that the number of antivasopressin positive neurons present in microphthalmic rats was only 68% of those found in normal rats. These findings suggest that the complete development of the SCN and vasopressin neurons depends on the visual input.

Animals↗

Exacerbation of hypothyroidism following tumor necrosis factor-alpha infusion.

A 46-year-old woman with chronic thyroiditis who had been receiving thyroid hormone treatment for 10 yr developed severe hypothyroidism (FT4 0.37 ng/dl, FT3 1.38 pg/ml, TSH 151.00 microU/ml) following tumor necrosis factor-alpha (TNF) infusion for the treatment of a complicated cutaneous T-cell lymphoma. Indirect immunofluorescence staining of thyroid follicular cells showed aberrant expression of HLA class II antigens. The mechanisms underlying the exacerbation of the hypothyroidism may be an augmentation of immunological processes in the thyroid and a direct action of TNF on the synthesis and secretion of thyroid hormone.

Female↗

[A newly designed salt bridge cap-type, a variable, and non-invasive EEG lead electrode and the analytical power spectrum].

A newly devised, variable EEG cap-style electrode that has an electrical salt bridge with 2% agarose gel and 5% NaCl solution was developed. The number of electrodes can be increased as required. The weight of 15 electrodes is about 100g. The electrode is simple, fast and in a one-touch form for measuring the EEG. An EEG using this electrode system was recorded in a healthy man in a sitting position on a chair, at rest, and with eyes closed. The power spectrum showed different patterns for the power at different concentrations of aqueous solution in the matrix of the salt bridge. The power changed to a pattern of J-type with 20% NaCl solution, to a pattern of U-type with 5% NaCl solution, and to a pattern of L-type with 0.9% NaCl solution, respectively. The matrix of the salt bridge that has a concentration higher than 0.9% NaCl, is a hypertonic solution for the isotonic body liquid. One person felt pain in half of the part of the experiment when a 20% NaCl hypertonic solution was applied to the scalp, so a 20% NaCl solution of the salt bridge was used in experiments concerning osmosis. When a salt bridge of 5% NaCl solution was used, the same results of the wave measurement was obtained 10 times. It was a value close to the expected measurement so it has a high probability of being correct. At this time the power spectrum shows a U-type pattern consistently.

Brain↗

[The frequency and mechanisms of urolithiasis in acromegaly].

It is generally accepted that acromegaly is often associated with hypercalciuria, but there are few reports on the frequency and the mechanisms of urolithiasis. Recently we consecutively experienced 2 cases of acromegaly with urolithiasis, and these experiences made us investigate the association between urolithiasis and acromegaly. Among 18 acromegalies from 1977 to March 1990 (10 males, 8 females, 24-64 years old), 13 cases (72%) fulfilled the criteria of hypercalciuria (urinary calcium (u-Ca) greater than or equal to 200 mg/day or u-Ca/urinary creatinine (u-Ca/u-Cr) greater than or equal to 0.15), and 7 cases (39%) suffered from urolithiasis that was diagnosed by KUB (4 cases) or X-ray computed tomography (CT) (3 cases). Especially in the last 2 years, 5 out of 7 cases (71%) were complicated with urolithiasis and all 7 cases were associated with hypercalciuria. These results suggest that hypercalciuria and urolithiasis are both much more frequent than previously reported. In 6 cases who were treated by pituitary adenomectomy from 1988-1989 (4 males, 2 females, 24-59 years old), we examined Ca metabolism before and after operation. Before operation, the levels of serum growth hormone (GH), u-Ca (mg/day), u-Ca/u-Cr (in all cases) and plasma somatomedin-C (Sm-C) (in 4 cases) were increased above the normal range. To determine the etiology of hypercalciuria, we performed the oral Ca load test under restriction of Ca (400 mg/day) and P (650 mg/day) intake. The results suggested that the hypercalciuria might be mainly due to the increased absorption of Ca from the intestine (so-called "Absorptive hypercalciuria"). However, the levels of serum vitamin D (Vit. D) metabolites were all within the normal range before operation. After operation, GH and u-Ca/u-Cr (in 5 cases) and u-Ca (mg/day) (in all cases) decreased significantly compared with before operation, and the levels of Sm-C (in all cases), serum 25-(OH)D3, 1 alpha, 25-(OH)2D3 (in 4 cases) and 24,25-(OH)2D3 (in 3 cases) were also reduced after operation. Surprisingly, u-Ca and u-Ca/u-Cr normalized only in 4 cases who showed a reduction in 1 alpha, 25-(OH)2D3 levels after operation, although there were no correlations between u-Ca (mg/day) or u-Ca/u-Cr and 1 alpha, 25-(OH)2D3. Significant correlations were found between u-Ca (mg/day) or u-Ca/u-Cr and Sm-C. The parathyroid function evaluated by the rapid Ca infusion test or nephrogenous cyclic adenosine monophosphate (NcAMP) was normal before and after operation.(ABSTRACT TRUNCATED AT 400 WORDS)

Acromegaly↗

Cyclosporine A (CyA)-induced decrease of serum gonadotropin levels in a case of Klinefelter's syndrome.

We report a case of Klinefelter's syndrome who developed a decrease of serum gonadotropin levels, particularly LH, after CyA treatment for complicated focal glomerulosclerosis (FGS). A 38-year-old man suffering from general malaise and pretibial edema was diagnosed FGS by renal biopsy in October 1988, and was referred to our hospital for further evaluation and treatment for FGS in December 1988. He was not married, and closer anamnesis revealed that he had had impaired seminal ejaculation from the age of 30. The physical examination showed 37% obesity, scanty body hair, pretibial edema and small bilateral testes (3.0 x 1.5cm). Laboratory findings included marked proteinuria (5.3g/day) and mild renal dysfunction (serum creatinine 1.3mg/dl, glomerular filtration rate 57.2ml/min). Endocrinologically, high basal levels of LH and FSH (133.6mIU/ml and 93.7mIU/ml, respectively) and the hyperresponses of LH and FSH to LH-RH stimulation were found, but the other pituitary hormone levels, thyroid and adrenal status, were in the normal range. In testicular biopsy, nodularly proliferated Leydig cells and no seminal tubules could be seen. The chromosome analysis showed 47,XXY karyotype, which confirmed the diagnosis of Klinefelter's syndrome in this patient. From 9 January 1989, CyA (6mg/Kg.day) was orally administered for 4 weeks in order to treat for FGS. After CyA administration, basal levels of LH and FSH remarkably decreased, particularly LH, and their decrease lasted for at least 6 weeks after cessation of CyA (final levels; LH 28.2mIU/ml, FSH 69.8mIU/ml). On the other hand, serum testosterone level was low normal or slightly under normal, and no apparent changes could be seen during CyA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Ultrastructural changes associated with reversal of chloroquine resistance by verapamil in Plasmodium chabaudi.

Reversal of chloroquine (CQ) resistance by verapamil, a Ca2+ antagonist, has been shown in CQ-resistant human and rodent malaria parasites. Here, we report ultrastructural changes associated with this phenomenon in CQ-resistant Plasmodium chabaudi (AS strain) after infected mice were administered CQ and verapamil. At parasitaemias of 5-7%, CQ at 6 mg/kg caused little morphological effect on CQ-resistant parasites. In contrast, co-administration of CQ and verapamil at 50 mg/kg induced swelling of food vacuoles with clumped pigment at 2.5 h. Morphological changes other than food vacuole enlargement occurred at 21 and 45 h: disappearance of endoplasmic reticulum, formation of myelin structures, focal cytoplasmic vacuolization and coarse clumping of electron-dense material in nuclei. These structural changes appeared to be very similar to those observed in CQ-sensitive P. chabaudi in mice injected with CQ alone or CQ plus verapamil. On the other hand, verapamil at 50 mg/kg alone did not induce any effect on both CQ-sensitive and CQ-resistant P. chabaudi. These results suggest that swelling of the food vacuoles is an initial event associated with reversal of CQ-resistance by verapamil.

Animals↗

Neuronal survival factor from bovine brain is identical to neuron-specific enolase.

Neuronal survival factors in the central nervous system were investigated by using a primary culture of embryonic rat neocortical neurons. Bovine hippocampus was homogenized, and the supernatant from high-speed centrifugation was used as the starting material. At the step of DE-52 ion-exchange chromatography, neuronal survival activity was recovered in two fractions, fraction 14 (F14) and fraction 23 (F23). Antisera to the crude F14 and F23 fractions were raised in rabbits. These two antisera completely inhibited the neurotrophic activity of both fractions. Western blotting analysis revealed that anti-F14 antiserum recognized mainly a 30-kDa protein in F14 and anti-F23 antiserum recognized mainly a 44-kDa protein in F23. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis of F23, the 44-kDa protein was cut out from the gel and partial amino acid sequences of the protein fragments were determined. A GenBank data bank indicated that the amino acid sequence of the fragment was identical to that of neuron-specific enolase (NSE). In our assay system, commercially available NSE itself possessed neuronal survival activity for the cultured neocortical neurons. The effects of NSE and F23 were inhibited completely by anti-NSE polyclonal antibody. Furthermore, highly purified NSE supported the survival of cultured neurons in a dose-dependent manner, and the neurotrophic effect was inhibited by monoclonal antibody to the NSE. These results strongly suggest that NSE is one of the neuronal survival factors in the central nervous system.

Animals↗

Oxygen dependence of lipid peroxidation in mice.

Peroxidation of lipids in serum and tissues of mice placed in low or high levels of oxygen was examined. After exposure to 100% oxygen for 3 h, no significant differences were observed between control and exposed mice. However, exposure to 100% oxygen for 6 h resulted in a decrease in oxygen consumption, an increase in lipid peroxides in tissues and serum, and the formation of hydroxyl radicals in tissues and serum. At low concentrations of oxygen (14% or 16%), a decrease in oxygen consumption, peroxidation of lipids and formation of hydroxyl radicals also were observed. Damage to mice was great with the lower oxygen concentrations of oxygen. There was a close correlation between the consumption of oxygen lipid peroxidation, formation of hydroxyl radicals.

Animals↗

Distribution pattern of pudendal nerve plexus for the phallus retractor muscles in the cock.

Two paired retractor muscles, m. retractor phalli cranialis (MRPCr) and m. retractor phalli caudalis (MRPCa) exist as the intrinsic cloacal muscles of the chicken. Pudendal plexus was formed by the ventral rami of roots 30-34. Pudendal nerve (PN) and the intermediated caudal nerve (ICN) were composed of twigs from roots 30-33 and roots 30-34, respectively. Two or three rootlets participated in the PN; its third one originated from the root 33 which is the first root of caudal trunk in pudendal plexus. The non-striated MRPCr was innervated by the PN, whereas the striated MRPCa by the ICN.

Animals↗

Determination of effective and safe dose for intracoronary administration of nicorandil in dogs.

STUDY OBJECTIVE: The aim was to evaluate the effective and safe dosage for intracoronary administration of nicorandil (2-nicotinamidoethyl nitrate) in dogs. DESIGN: Five ml of saline with or without nicorandil (0.025, 0.25, 1.0 or 2.5 mg) was constantly infused into the left anterior descending coronary artery (LAD) in 1 min without blood flow reduction in group A (normoxic group, n = 5) and with 50% blood flow reduction of the control value in group B (ischaemic group, n = 5). SUBJECTS: 10 mongrel dogs of either sex were used, weight 14.6-20.5 kg. MEASUREMENTS AND MAIN RESULTS: The myocardial weight of the perfused area was 33.2(SD 7.9) g. In group A, LAD blood flow increased from 28.4(8.6) to 86.3(25.0) ml.min-1, p less than 0.05, following intracoronary infusion of 0.25 mg nicorandil. Higher doses caused no further increase. In both groups, high doses (1.0 mg or more) suppressed regional myocardial contraction, expressed as % segment shortening, from 20.0(4.7) to 10.0(9.0)%, p less than 0.05, in group A, and from 12.7(8.5) to 6.5(5.6)%, p less than 0.05, in group B. Multiple ventricular premature beats developed in both groups only at the dose of 2.5 mg: 6.8(5.5) beats.min-1 in group A and 4.5(4.2) beats.min-1 in group B. Ventricular fibrillation developed in two dogs in group B. Nicorandil did not affect the local bipolar electrocardiogram of the subendo- and subepicardium in the perfused area in either group. CONCLUSIONS: Intracoronary administration of 0.25 mg of nicorandil was effective for coronary vasodilatation without deleterious mechanical or electrical effects. Larger doses of the agent showed adverse effects depending on the dosages.

Animals↗

[A case of hepatocellular carcinoma treated by intrahepatic arterial administration of anticancer agents: serial determination of the concentration of the chemotherapeutic agents in serum and dialysate during hemodialysis].

The concentration of adriamycin (ADR) and mitomycin C (MMC) were measured in serum and dialysate in a patient with hepatocellular carcinoma complicating chronic renal failure. ADR at a dose of 20 mg and MMC at 10 mg were administered through the hepatic artery or peripheral vein during hemodialysis. ADR and MMC became undetectable after 24 hours and 2 hours, respectively. On the other hand, while MMC was detected in dialysate, but ADR was not. Consequently, it was speculated smaller molecular weight of MMC (334.34) than that of ADR (579.99) might be responsible for the appearance of MMC in dialysate. These results suggest that hemodialysis may be effective in reducing side effects of certain anticancer agents. Serum concentration of the anticancer agents injected through hepatic artery was similar to that injected intravenously.

Adult↗

Distribution of acetylcholinesterase in the nerve endings of chicken m. retractor phalli cranialis.

The distance of the neuromuscular gap was measured in a chicken smooth muscle, m. retractor phalli cranialis (MRPC). For the identification of active neuromuscular contacts, acetylcholinesterase (AChE) was stained according to Tago's modification of the Karnovsky and Roots' method. Thirty two out of 500 muscle cells were within 200 nm from the nerve endings. The MRPC was classified as Burnstock's Model C, which is characterised by the low frequency of directly innervated cells. The AChE-positive reaction was observed on both muscular and neural membranes only when the distance between the two was less than 170 nm. These results suggest that the smooth muscle cells may be innervated by axon varicosities within such a distance.

Acetylcholinesterase↗

[Research into actual conditions and preventive care in periodontal disease. Relationship between questionnaire results and periodontal disease in youth].

The purpose of this study was to determine the prevalence of periodontal disease and the relationship between the results of questionnaire concerning periodontal disease and the actual periodontal condition in youth. The examination was carried out in three parts. In the first part, a questionnaire was conducted on 3,886 junior and senior high school students (12 to 18 years of age) living in Kawagoe, Japan. The questionnaire was composed by of items concerning habits of oral hygiene, periodontal symptoms, understanding of periodontal disease and history of diagnosis by dentist of periodontal disease. Secondary, mass intraoral examination was carried out on all objects. The examination covered gingival inflammation, periodontal probing depth, calculus, dental plaque, dental caries and malalignment. Lastly, we examined the relationship between the results of periodontal examination and questionnaire with the original periodontal classification. The following results were obtained: 1. As an example of items in questionnaire, 83.1% brushed their teeth more than two times daily. The understanding of oral hygiene concerning dental caries was improved, but concerning periodontal disease was still poor. 2. The symptom most frequently reported was gingival bleeding during tooth brushing (18.4%). 3. The percentage of persons with periodontal disease (moderate gingival inflammation and periodontal pocket 4 mm or deeper) was of the highest frequency at 13 years old. The proportion of males increased with the advanced state of periodontal disease. 4. A significant correlation was found (chi 2-test: alpha less than 0.001) between advanced state of periodontal disease and a decrease in tooth brushing time per day. 5. A significant correlation was found between the advance of periodontal disease and gingival bleeding on tooth brushing (chi 2-test: alpha less than 0.001). Similarly, a correlation was found between the advance of periodontal disease and gingival swelling (chi 2-test: alpha less than 0.001). 6. A significant correlation was found (chi 2-test: alpha less than 0.001) between the advance of periodontal disease and aggravation of condition of dental plaque, calculus, dental caries and malalignment.

Adolescent↗

Ultrastructural identification of axons supplying the M. retractor phalli cranialis in chickens.

The chicken m. retractor phalli cranialis classified as a smooth muscle was examined by electron microscopy to study the innervation of this muscle using the dichromate/chromate fixation method for demonstration of biogenic amines (Tranzer and Richards, 1976). Approximately two axon complexes per 100 muscle cells were found in both sexes. The axon varicosities were divided into the following four types; varicosities with, 1) small clear vesicle and chromaffin-negative large granular vesicle (cholinergic), 2) chromaffin-positive, 6-hydroxydopamine (6-OHDA) susceptible small and large granular vesicle (adrenergic), 3) chromaffin-positive, 6-OHDA resistant pleomorphic and large granular vesicle (aminergic?), or 4) chromaffin-negative large opaque vesicle (peptidergic?). These results suggest that non-adrenergic, non-cholinergic nerve may also play an important role in the innervation of m. retractor phalli cranialis as well as of the smooth muscle in mammalian intestine.

Animals↗

Complete nucleotide sequence of human vasoactive intestinal peptide/PHM-27 gene and its inducible promoter.

We have previously shown that the VIP precursor contains a novel PHI-27-like peptide, PHM-27, and that the synthesis of the prepro-VIP/PHM-27 mRNA is induced with cAMP and TPA in human neuroblastoma cells. In this study, we have determined the complete nucleotide sequence of the human VIP/PHM-27 gene. The gene spans 8,837 bp and consists of seven exons and six introns. Exon I of 165 bp consists of the 5' untranslated region of the gene, exon II of 117 bp encodes the signal peptide of prepro-VIP/PHM-27, exon III of 123 bp encodes the amino-terminal region, exon IV of 105 bp encodes PHM-27, exon V of 132 bp encodes VIP, exon VI of 89 bp contains the termination codon of the prepro-VIP/PHM-27 mRNA, and exon VII of 724 bp consists of the 3' untranslated region of the gene. VIP and its structurally related peptide, PHM-27, were encoded in different exons V and IV, and the sequences around the splice junctions between these exons and their adjacent introns were highly conserved, suggesting that the VIP-encoding and PHM-27-encoding exons have been duplicated from an ancestral exon over a broad area containing its adjacent introns. We also determined the 1,929-bp sequence of the 5' flanking region of the human VIP/PHM-27 gene and found that four TATA-box sequences were present at 28 bp, 145 bp, 772 bp, and 900 bp upstream of the cap site. Primer extension, exon mapping, and mung bean nuclease mapping analyses revealed that only the TATA-box sequence 28 bp upstream of the cap site was the promoter that is inducible by cAMP and TPA in the human neuroblastoma cells. An 18-bp sequence 52 bp upstream from the TATA-box sequence was suggested to be a cAMP/phorbol esters-responsive element of the human VIP/PHM-27 gene.

Base Sequence↗