Axonal projection of descending pathways responsible for eliciting forelimb stepping into the cat cervical spinal cord

Summary The descending pathways responsible for eliciting forelimb stepping are located in the lateral funiculus (Yamaguchi 1986). In order to determine into which spinal segments the descending pathways project and to know the projections and functions of the other descending system, the ventral funicular pathways, we placed various lesions in the cervical spinal cord of decerebrate cats with the lower thoracic cord transected and studied their effects on forelimb stepping evoked by stimulation of the midbrain locomotor region. (1) The lateral funiculus was transected on one side. The operation removes descending input to all the segments caudal to the lesion. Experiments with serial transections from the caudal to rostral segment revealed that stepping activity of the limb on the lesioned side is reduced when the lesion is placed at the level between the C6 and C7 segment and then between C5 and C6. A slight reduction of activity was also observed after a lesion placed between C7 and C8. (2) Consistently, bilateral transection of the lateral funiculus at the level between C5 and C6 abolished stepping movements of both forelimbs. (3) The cervical cord was split in the parasagittal plane through the dorsal root entry. The operation removes the descending input to the segment in which the lesion is placed. The parasagittal lesions from the C1 to C6 did not abolish stepping activity, although a lesion placed between C5 and C6 could slightly affect stepping. The results, (1)–(3) suggest that the lateral funicular pathways project into the spinal segments mainly at the C6–C7 level with some rostrocaudal extension into C5 and C8. (4) Complete transections of the medial part of the spinal cord cut extensor bursts short and raised stepping frequency. Nevertheless, if the lesion at C1–C5 spared the ventromedial part of the ventral funiculus, it did not result in such high-frequency stepping or in weakened extensor activity. In the case of segments caudal to C6, medial transections which spared the corresponding region could result in such stepping. It is suggested that the pathways descending through the ventromedial part of the ventral funiculus in the rostral segments provide extensor activity during stepping. They may change their course in the more dorsal part of the ventral funiculus below the C6 and presumably project into the grey matter of more caudal segments.     

Suppressive effects of E3330, a novel quinone derivative,on tumor necrosis factor-α generation from monocytes and macrophages

E3330 {(2E)-3-[5-(2,3-dimethoxy-6-methyl-1,4-benzoquinoyl)]-2-nonly-2-propenoic acid}, a novel synthesized hepatoprotective compound, has suppressive effects on tumor necrosis factor- (TNF-) generation from monocytes/macrophagesin vitro. E3330 (1–100 M) reduced lipopolysaccharide (LPS, 10 mg/ml or 1g/ml)-induced TNF- generation from rat resident andPropionibacterium acnes (P. acnes)-elicited peritoneal macrophages, rat and human monocytes, rat Kupffer cells, and splenic mononuclear cells in a concentration-dependent manner. E3330 also (1–100 M) suppressed TNF- generation stimulated with egg-albumin immune complex in ratP. acnes-elicited peritoneal macrophages. Northern blot analysis showed that LPS-induced expression of TNF- messenger RNA (mRNA) in human blood monocytes was suppressed by E3330. These findings indicate that E3330 has a suppressive effect on TNF- generation from monocytes/macrophages, regardless of origin or species, and this effect is based in part on the suppression of TNF- mRNA expression.     

Cervical interneurones oligosynaptically excited from primary afferents and rhythmically active during forelimb fictive locomotion in the cat

In C6-C7, activity of neurones oligosynaptically excited from primary afferents was examined during fictive locomotion. Two kinds of neurones were found: neurones with activity modulated and with activity not modulated. The minimum linkage of the pathway to modulated neurones was mono- and disynaptic from muscle and cutaneous afferents, respectively, while non-modulated neurones were monosynaptically excited from both afferents. Modulated neurones were mainly located in the ventral part of the dorsal horn and adjoining intermediate region, non-modulated ones located in the dorsal horn. Modulated neurones were found near motor nuclei as well. Active periods of modulated neurones were widely distributed in the step cycle.     

Uptake of99mTc-tetrofosmin,99mTc-MIBI and201TI in malignant thymoma

99mTc-tetrofosmin, Thallium-201-chloride (201Tl) and 99mTc-MIBI imagings were performed in a patient with malignant thymoma. Tracer uptake in the primary tumor was demonstrated. The tumor-to-background ratios of planar and SPECT imagings were 1.60 and 1.98 for 99mTc-tetrofosmin, 1.12 and 2.09 for 201Tl, and 1.19 and 1.80 for 99mTc-MIBI, respectively. In another patient 99mTc-tetrofosmin and 201Tl imagings were performed. Not only the primary tumor but also the direct invasions and metastatic lesions (bone metastases) were clearly detected. The tumor-to-background ratios of planar and SPECT imagings were 2.31 and 2.78 for 99mTc-tetrofosmin and 2.45 and 3.58 for 201Tl, respectively. In 99mTc-tetrofosmin scintigraphy we acquired delayed images, and the tumor-to-background ratios of planar and SPECT delayed images were 1.20 and 1.86, the retention ratios were -1.11 and -0.92 and the retention indices were -48.1 and -33.1, respectively. Our preliminary results suggest that 99mTc-tetrofosmin is useful in detecting not only the primary tumor but also metastatic lesions from malignant thymoma.     

Longitudinal Prediction of Suicide Attempts for a Diverse Adolescent Sample of Native Hawaiians,Pacific Peoples,and Asian Americans

The objective of this study was to determine the longitudinal predictors of past-6-month suicide attempts for a diverse adolescent sample of Native Hawaiians, Pacific peoples, and Asian Americans. The study used longitudinal data from the Hawaiian High Schools Health Survey (N?=?2,083, 9th to 11th graders, 1992–1993 and 1993–1994 school years). A stepwise multiple logistic regression was conducted. The final model consisted of three statistically significant predictors: (1) Time 1 suicide attempt, odds ratio?=?30.6; (2) state anxiety, odds ratio?=?4.9; and (3) parent expectations, odds ratio?=?1.9. Past suicide attempt was by far the strongest predictor of future suicide attempts. Implications are discussed, including the need for screening of prior suicide attempts and focused interventions after suicide attempts.     

Gene Expression Analysis Using a High‐Resolution DNA Microarray of Peripheral Whole Blood Immediately Before and After Leukocytapheresis for Rheumatoid Arthritis

Leukocytapheresis (LCAP) is a safe, unique therapy pertaining to intractable rheumatoid arthritis (RA) even in cases of drug allergy or infectious states. To investigate how to represent LCAP efficacy, we have conducted gene expression analyses from the peripheral blood of RA patients treated with non‐woven polyethylene terephthalate filters. Peripheral blood samples were collected immediately before and after treatment from eight RA patients who received LCAP. Among these patients, all of them achieved 20% improvement in the core set of the American College of Rheumatology (ACR20), and thus, they were confirmed as LCAP responders. Gene expression analysis was done with a high‐resolution DNA microarray. The results of each of the two groups' gene expression values (immediately before and after LCAP) were calculated using Welch's t‐test. Calculations were performed with a statistical software R.basic package: if the P‐value was less than 0.05, this was seen as a significant change. In a comparison of 25 370 gene expressions, the number of genes showing a P‐value < 0.05 in the upregulating group was 2110, and in the downregulating group it was 1864. The results of pathway analysis using the MetaCore program indicate that gene groups work for cytoskeletal remodeling are upregulated, and genes related to immune responses, such as antigens presenting via major histocompatibility complex class I and II, are downregulated just after LCAP. These findings may relate to LCAP efficacy for RA patients, but this needs further investigation.     

Transient hypothyroidism or persistent hyperthyrotropinemia in neonates born to mothers with excessive iodine intake.

Perinatal exposure to excess iodine can lead to transient hypothyroidism in the newborn. In Japan, large quantities of iodine-rich seaweed such as kombu (Laminaria japonica) are consumed. However, effects of iodine from food consumed during the perinatal period are unknown. The concentration of iodine in serum, urine, and breast milk in addition to thyrotropin (TSH), free thyroxine (FT(4)), and thyroglobulin was measured in 34 infants who were positive at congenital hypothyroidism screening. Based on the concentration of iodine in the urine, 15 infants were diagnosed with hyperthyrotropinemia caused by the excess ingestion of iodine by their mothers during their pregnancy. According to serum iodine concentrations, these infants were classified into group A (over 17 microg/dL) and group B (under 17 microg/dL) of serum iodine. During their pregnancies these mothers consumed kombu, other seaweeds, and instant kombu soups containing a high level of iodine. It was calculated that the mothers of group A infants ingested approximately 2300-3200 microg of iodine, and the mothers of group B infants approximately 820-1400 microg of iodine per day during their pregnancies. Twelve of 15 infants have required levo-thyroxine (LT(4)) because hypothyroxinemia or persistent hyperthyrotropinemia was present. In addition, consumption of iodine by the postnatal child and susceptibility to the inhibitory effect of iodine may contribute in part to the persistent hyperthyrotropinemia. We propose that hyperthyrotropinemia related to excessive iodine ingestion by the mother during pregnancy in some cases may not be transient.     

Differential thermodynamic driving force of first- and second-generation antihistamines to determine their binding affinity for human H1 receptors

Differential binding sites for first- and second-generation antihistamines were indicated on the basis of the crystal structure of human histamine H₁ receptors. In this study, we evaluated differences between the thermodynamic driving forces of first- and second-generation antihistamines for human H₁ receptors and their structural determinants. The binding enthalpy and entropy of 20 antihistamines were estimated with the van’t Hoff equation using their dissociation constants obtained from their displacement curves against the binding of [³H]mepyramine to membrane preparations of Chinese hamster ovary cells expressing human H₁ receptors at various temperatures from 4 °C to 37 °C. Structural determinants of antihistamines for their thermodynamic binding properties were assessed by quantitative structure–activity relationship (QSAR) analyses. We found that entropy-dependent binding was more evident in second- than first-generation antihistamines, resulting in enthalpy–entropy compensation between the binding forces of first- and second-generation antihistamines. QSAR analyses indicated that enthalpy–entropy compensation was determined by the sum of degrees, maximal electrostatic potentials, water-accessible surface area and hydrogen binding acceptor count of antihistamines to regulate their affinity for receptors. In conclusion, it was revealed that entropy-dependent hydrophobic interaction was more important in the binding of second-generation antihistamines, even though the hydrophilicity of second-generation antihistamines is generally increased. Furthermore, their structural determinants responsible for enthalpy–entropy compensation were explored by QSAR analyses. These findings may contribute to understanding the fundamental mechanisms of how the affinity of ligands for their receptors is regulated.