Acquired posttransplantation hair kinking.
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Biomedical subjects
Publications and source records attributed to K Hashimoto.
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We present two patients with subcutaneous fat necroses (SCFN) in whom endocrinologic studies revealed an association with elevated prostaglandin E (PGE) levels. A boy born after prolonged labor complicated by meconium aspiration developed erythematous, indurated plaques over the back, arms, buttocks, and cheeks at 4 days of age. A biopsy specimen of involved skin showed panniculitis with foci of necrotic adipocytes containing radially arranged, needle-shaped clefts and a granulomatous infiltrate in the septae. Laboratory studies revealed hypercalcemia of 13.6 mg/dl (normal 8.8-10.1 mg/dl), elevated 1.25-1.25(OH)2D3, and increased urinary excretion of PGE2. The child was hospitalized and treated with systemic steroids and diuretics, with resolution of SCFN and hypercalcemia. The second patient was a girl born with cyanotic heart disease. A diagnosis of Ebstein anomaly was made, and intravenous PGE1 was started to keep patent the ductus arteriosus. Four days later erythematous, indurated plaques were noted on the knee, back, and anterior chest. A skin biopsy specimen revealed SCFN. There was no associated laboratory abnormality. On discontinuing PGE1, no new lesions formed and the existing panniculitis resolved. These two cases demonstrate the association between SCFN and elevated PGE levels (endogenous in patient 1, exogenous in patient 2). No previous reports of SCFN after the administration of PGE1 have appeared in the literature.
A new patient with CHILD syndrome (congenital hemidysplasia, ichthyosiform erythroderma, and limb defects), the thirtieth in the literature, was observed for over three years. Initially, the right-sided lesion spared the breast area. At 10 months of age the trunk lesion extended to cover the entire area of the right chest. At age 20 months the patient developed linear, bandlike, keratotic, brown-black lesions on her left thigh that subsided within six weeks, leaving a slight hyperpigmentation. This patient was studied by routine histologic methods as well as with markers of keratinization and electron microscopy. In hematoxylin and eosinstained sections, parakeratosis and orthokeratosis alternated. In some parakeratotic areas, large granular cells, and in others, ghost granular cells, were present. The latter showed basophilic cytoplasm, and palestaining or vacuolated nucleus and were seen either above the normal granular layer or without it. Although regional variations existed, basal cell-type keratins as recognized by AE1 continued to be expressed in suprabasal layers. Filaggrin- and involucrin-positive layers were expanded, particularly the latter, down to the lower prickle cell layer. Ultrastructurally, numerous lamellar or membranous structures were found in upper layers of the epidermis, both intracellulary and intercellularly. Normal cementsomes coexisted with these abnormal lamellar structures, and it was thought that the latter represent modified cementsomes because the discharge of those from the cell periphery was often detected.
Inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP) is a novel glycoprotein isolated from human plasma. The cDNA encoding IHRP has recently been cloned from human liver cDNA libraries. We report the mapping of this gene (ITIHL1) by fluorescence in situ hybridization using a 2.5-kb cDNA fragment as a probe. ITIHL1 was localized to chromosome region 3p21-->p14 where the genes of heavy chain 1 and 3 of inter-alpha-trypsin inhibitor are located. This result, together with significant homology between the nucleotide sequences of ITIHL1 and the heavy chain genes, supports ITIHL1 as being a member of an evolutionary related gene family of ITI heavy chains. Northern blot analysis indicated that IHRP was predominantly synthesized in liver. From Southern blot analysis, it was tentatively concluded that ITIHL1 is a single copy gene.
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Endothelins exert potent excitatory cardiac effects by acting on specific receptors on myocytes. In this study, we have examined the signal transduction mechanism for the chronotropic effect of endothelins in guinea pig atria. A competition binding of [125I]endothelin 1 ([125I]ET-1) using the recently developed ETA receptor-selective antagonist BQ123 showed the presence of almost equal populations of ETA (44%) and ETB (56%) receptors in the guinea pig right atria. In a concentration-response study, endothelin 3 (ET-3), an agonist with higher affinity to ETB receptors than to ETA receptors, and sarafotoxin S6c (STXS6c), an ETB receptor-selective agonist, increased the rate of spontaneous beating at all concentrations tested (10 pmol/L to 100 nmol/L). In contrast, ET-1, a nonselective agonist, increased the heart rate at lower concentrations (10 pmol/L to 10 nmol/L) but decreased it at higher concentrations (30 to 100 nmol/L). When ET-1 (100 nmol/L) was applied in a single amount, heart rate was strongly increased; however, this increase was followed by a rapid decline in the response. ET-1 (100 nmol/L) but not ET-3 or STXS6c significantly reduced the heart rate when it was raised by isoproterenol (ISO, 300 nmol/L) either in the absence or presence of a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX). Correspondingly, ET-1 significantly reduced the ISO-induced elevation of cAMP accumulation (19.1 +/- 1.7 pmol/mg protein [n = 8] and 12.6 +/- 1.2 pmol/mg protein [n = 7] in the absence and presence of ET-1, respectively; P < .01), which was also observed even in the presence of IBMX.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND AND PURPOSE: We tested the hypothesis that administration of 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP), a potent sigma-receptor ligand, during transient focal ischemia would affect early postischemic brain injury. METHODS: Halothane-anesthetized cats underwent left middle cerebral artery occlusion for 90 minutes followed by 4 hours of reperfusion. Control cats received saline (n = 10). Experimental cats (2 groups, n = 10 per group) were treated with PPBP at a rate of 0.1 mumol/kg per hour (PPBP-0.1) or administered 1 mumol/kg per hour (PPBP-1) intravenously from 75 minutes after initiation of ischemia and continuing during the 4 hours of reperfusion. RESULTS: As measured by the microsphere method, blood flow to the ipsilateral caudate nucleus was decreased similarly in all groups during ischemia. Blood flow to the ipsilateral inferior temporal cortex was decreased during ischemia in all groups but was higher in cats subsequently treated with PPBP at the highest dose, even before drug administration. There was no difference in blood flow to the ipsilateral caudate nucleus or inferior temporal cortex (area of greatest cortical injury) during reperfusion. Triphenyltetrazolium-determined injury volume of the ipsilateral cerebral hemisphere (control, 29 +/- 5%; PPBP-0.1, 17 +/- 3%; PPBP-1, 6 +/- 1% of ipsilateral hemisphere; mean +/- SEM) and caudate nucleus (control, 49 +/- 5%; PPBP-0.1, 39 +/- 6%; PPBP-1, 25 +/- 5% of ipsilateral caudate nucleus) was less in cats treated with 1 mumol/kg per hour of PPBP compared with cats treated with saline. Cats treated with 0.1 mumol/kg per hour had a 45% smaller hemispheric injury volume than the control group without differences in intraischemic blood flow. Recovery of somatosensory evoked potential amplitude was greater in cats treated with PPBP-1 compared with control (control, 18 +/- 11%; PPBP-0.1, 30 +/- 14%; PPBP-1, 54 +/- 14% of baseline). CONCLUSIONS: These data indicate that sigma-receptors may play an important role in the mechanism of acute injury in both the cortex and the caudate nucleus after 90 minutes of transient focal ischemia in the cat. Because PPBP afforded protection when administered at the end of ischemia and during reperfusion, sigma-receptors may contribute to the progression of injury in ischemic border regions.
Transient cortical blindness, an uncommonly recognized complication of cerebral angiography, is an exceedingly rare event after cardiac catheterization and angiography. This report describes a sixty-two-year-old patient who had transient cortical blindness following bypass graft angiography. In this case, the authors showed that cortical blindness was associated with the breakage of the blood-brain barrier (BBB) and an increase in vascular permeability rather than with primary cerebral circulatory insufficiency. When the possibility exists that an excess volume of contrast medium may enter the cerebral circulation as in this case, that is, following a coronary artery bypass graft (CABG) using the internal mammary artery (IMA), precautionary measures may be necessary such as changing the type of contrast medium to be used or decreasing the volume injected. When cortical blindness occurs, it is a serious clinical problem whether transient or permanent. Therefore, the circumstances leading to this complication should be understood to determine suitable treatment and management.
The expression of GHRH receptor (GHRH-R) messenger ribonucleic acid (mRNA) was studied in 22 pituitary adenomas and 2 normal anterior pituitaries. Northern blot analysis revealed that GHRH-R mRNA were expressed in all 14 GH-producing adenomas, 1 of 3 ACTH-producing adenomas, the 1 PRL-producing adenoma, 2 of 4 nonfunctioning adenomas, and the 2 normal anterior pituitaries. Their expression levels varied among GH-producing adenomas and were relatively low in GH-nonproducing adenomas. In addition to the major transcript with a molecular mass of 2.0 kilobases (kb), the transcripts were identified at 2.8 and 4.5 kb in some GH-producing adenomas. To examine the structural variations in GHRH-R mRNA in pituitary adenomas, we amplified the complementary DNA fragment encompassing the region from the third cytoplasmic loop to the sixth transmembrane domain of GHRH-R. This region was selected because this region of the G protein-coupled receptor has been known to interact with G protein. Two amplified fragments with the molecular masses of 250 and 810 base pairs were identified by the reverse transcriptase-polymerase chain reaction method. The nucleotide sequence of a smaller fragment, which was the expected size, revealed that no mutations were found in this region in 10 GH-producing adenomas examined. However, a larger fragment contained the currently unidentified insertion. Compared with the genomic DNA sequence, this insertion was found to be generated through alternative splicing. In addition, this variant form contained the premature stop codon in-frame, indicating that it encodes the truncated GHRH-R. This insertion-specific probe could hybridize with 2.8- and 4.5-kb species of GHRH-R mRNA on Northern blot analysis, and these transcripts were expressed mainly in GH-producing adenomas. Finally, study of cell transfection and cAMP measurement revealed that this truncated GHRH-R was unable to transmit GHRH signals. These results suggest that some GH-producing adenomas preferentially express the truncated GHRH-R as a nonfunctioning receptor through alternative splicing.
We investigated the role of leukemia inhibitory factor (LIF) at the implantation site of human embryos. The first trimester decidual tissue produced higher levels of LIF than chorionic tissue, but the decidua produced much smaller amounts of interleukin-6 (IL-6) than the chorion in vitro, as determined by enzyme-linked immunosorbent assay. The reverse transcription-polymerase chain reaction and immunohistochemical analysis revealed the expression and localization, on the trophoblasts, of glycoprotein 130 (gp130), an IL-6 signal transducer receptor component shared by the cytokines such as LIF and IL-6. Trophoblasts stimulated by recombinant LIF (rLIF) produced CG titer at the amount similar to that induced by rIL-6. Recombinant LIF-induced CG production was significantly blocked by anti-gp130 antibody but not by anti-IL-6 receptor antibody, whereas rIL-6-induced CG was completely blocked by both antibodies. Recombinant LIF- and rIL-6-induced CG productions were both significantly blocked by genistein, a tyrosine kinase inhibitor, suggesting an involvement of tyrosine kinase in gp130-mediated CG production. Since CG is capable of stimulating trophoblast growth and differentiation as well as placental metabolism, LIF produced at the fetomaternal interface are considered to stimulate the trophoblasts to produce CG, which may contribute to the maintenance of the placental functions and embryonal growth.
The antiarrhythmic effects of a new class III antiarrhythmic agent, MS-551 [1,3-dimethyl-6-(2-[N-(2-hydroxyethyl)-3-(4-nitrophenyl) propylamino]ethylamino)-2,4(1H,3H)-pyrimidinedione hydrochloride], were investigated using canine coronary ligation-reperfusion arrhythmia models under slow and fast heart rate conditions and compared with those of d-sotalol. Slow and fast heart rate conditions were produced by using different anesthetics; i.e., halothane anesthesia for the slow heart rate condition and pentobarbital Na anesthesia for the fast heart rate condition. MS-551 prolonged QTc and suppressed the occurrence of fatal ventricular fibrillation (VF) on coronary reperfusion under either halothane or pentobarbital anesthesia. However, it also showed proarrhythmic effects, i.e., induction of torsades de pointes-like arrhythmia in 1 of 6 halothane anesthetized dogs before coronary ligation. d-Sotalol did not suppress the reperfusion VF in halothane anesthetized animals, nor did it show proarrhythmic effects. However, in the pentobarbital anesthetized animals, d-sotalol suppressed reperfusion VF accompanied by proarrhythmic effects in 1 of 7 dogs. d-Sotalol did not show reverse rate dependent QT prolongation. These results indicate that although both these class III drugs have similar electrophysiological properties, such as QTc prolongation, they have different antiarrhythmic effects. Also, antifibrillatory effects of class III drugs on coronary reperfusion apparently can not be explained solely by their QT prolonging effects.
Antiarrhythmic effects of bisaramil were examined by using new in vivo triggered arrhythmia models, and they were compared with those of other antiarrhythmic drugs. Bisaramil (3-10 micrograms, i.c.) suppressed triggered ventricular arrhythmias that were produced during pauses between trains of rapid ventricular stimulation (cycle length: 250 msec, train number: 15) in anesthetized open-chest dog hearts administered with subtoxic doses of digitalis or adrenaline to the anterior descending coronary artery. The potencies of bisaramil, disopyramide, lidocaine and flecainide suppressing digitalis-induced triggered ventricular arrhythmias were similar to those suppressing adrenaline-induced ones. The potency of verapamil for suppressing digitalis-induced triggered ventricular arrhythmias were weaker than that for suppressing the adrenaline-induced ones. Bisaramil was the most effective among the antiarrhythmic drugs used in the present experiment. Since bisaramil has been reported to be effective in suppressing other canine automatic ventricular arrhythmias, and the triggered ventricular arrhythmias occur in clinical situations, bisaramil may become a useful drug for the treatment of clinical arrhythmias.
We used octreotide to treat a woman with acromegaly and observed pituitary adenoma shrinkage after 5 months. Diffuse scalp hair loss occurred after 5 months, resulting in the discontinuation of treatment. After the cessation of octreotide, the hair loss stopped and hair growth resumed. Since bromocriptine did not effectively decrease the GH level of the patient, we decided to perform transsphenoidal surgery. After resection of the pituitary adenoma, her GH and IGF-1 levels were normalized. Although octreotide-induced scalp hair loss has not been well recognized, we should pay more attention to this side effect.
To investigate the role of nitric oxide (NO) in pituitary ACTH secretion, the effect of a nitric oxide synthase (NOS) inhibitor, N omega-Nitro-L-arginine (Nitro-Arg), on ACTH secretion induced by interleukin (IL)-1 beta, corticotropin releasing hormone (CRH), arginine vasopressin (AVP) and phorbol myristate acetate (PMA) was examined in rat anterior pituitary cell cultures. Nitro-Arg did not affect IL-1 beta-induced ACTH release in pituitary cell cultures incubated with Dulbecco modified Eagle's medium, Basal Medium Eagle or Krebs Ringer bicarbonate-glucose buffer. It did not affect CRH-, AVP- or PMA-induced ACTH release either. These results suggest that NO does not play an important role in ACTH release at the pituitary level.
Many reports dealing with the toxicity of oil mist in industrial health have been published. The condition appears to be worldwide in distribution and the number of reported cases increases with increasing clinical awareness. In 158 reports published from 1965 to 1993 the following diseases were observed: Skin--contact dermatitis, oil acne and photosensitive allergic dermatitis; Scrotum--benign and malignant tumors; Respiratory system-nasal discomfort symptoms, rhinitis, nasal mucosal dysplasia, nasal mucosal tumor, laryngeal cancer, bronchitis, lipoid pneumonia, lung fibrosis, lung cancer and bronchial asthma; Others--possible carcinogenicity, high incidence of chromosomal change. This shows that oil mist appears to be involved in many industrial diseases, however, cause-and-effect relationship still remains a matter of conjecture; in which exposure dose and/or duration-dependent toxicity is highly probable. Further investigations will be required including immunotoxicological as well as environmental studies for oil mist exposure.
Pyrethroid insecticides induce two different clinical symptoms. The difference has been reported to depend on the effect on the sodium channel opening time. We performed the present study to confirm this report by a double stimulation method. Allethrin (type I) 5 mg/kg and fenvalerate (type II) 1.5 kg/mg were injected into pentobarbital anesthetized rats. Tail nerve excitability was examined by a double stimulation method at from 4 msec to 40 msec intervals. The excitability was expressed as a percentage of the response to conditioned stimuli following supernormal stimuli to response to unconditioned stimuli. In control rats, the largest excitability was 94.6 +/- 19.2% at an 8 msec stimulus interval. After allethrin injection, we obtained two types of excitability changes. In some rats, supernormal excitability was present from 4 msec to 15 msec up to 120%. In other rats, the excitability was lower than that in the control from 4 msec to 15 msec. In fenvalerate treated rats, there was supernormal excitability from 4 msec to 40 msec. The peak of excitability was 122.4 +/- 35.3% at 10 msec. By double stimulation methods, we obtained characteristic nerve excitability changes in allethrin and fenvalerate treated rats after symptoms disappeared. These results showed that it should be possible to detect human nerve subclinical changes following lower doses or during chronic exposure.
We present three elderly Japanese patients with abrupt onset of diabetes mellitus: a 61-year-old male with a complete defect of insulin secretion without insulin resistance, a 60-year-old male with an incomplete defect of insulin secretion associated with insulin resistance, and a 69-year-old female with a complete defect of insulin secretion and insulin resistance. The findings in these cases indicate the heterogeneity in insulin secretion and sensitivity of abrupt onset diabetes mellitus in the elderly. The changes in insulin secretion and sensitivity over time due to glucose toxicity may at least partially explain the heterogeneity.
A 62-year-old woman was initially hypothyroid and then developed hyperthyroidism with continuously positive thyroid-stimulating antibody (TSAb). When she visited our hospital with the complaint of the feel of skipping beats, her serum free T4 level was initially low and thyrotropin (TSH) level was slightly elevated. One month after starting the supplement therapy with l-T4, she developed hyperthyroidism with increased 123I-thyroid uptake. TSH-binding inhibitor immunoglobulin (TBII) was slightly elevated only during the hypothyroid stage. Throughout the whole course, TSAb was continuously positive, while thyroid stimulation-blocking antibody (TSBAb) was not detectable. Primary hypothyroidism with TSAb may suggest the possibility of subsequent development of hyperthyroidism.