Favourable swallowing outcomes after subtotal glossectomy with laryngeal suspension.

Subtotal or total glossectomy for advanced tongue cancer has an adverse impact on swallowing. The purpose of this retrospective study was to analyse postoperative swallowing outcomes and to determine the ideal reconstruction method in these patients. The clinical and swallowing data of patients with tongue cancer who underwent subtotal glossectomy at the study institution between 2005 and 2019 were reviewed retrospectively. Data were available for 101 patients. The most common reconstruction method was a free rectus abdominis musculocutaneous flap (69 cases). The postoperative feeding tube dependency rate was 11.1% at discharge and 9.4% at 1 year. During the study period, laryngeal suspension and/or a cricopharyngeal myotomy was performed in 39 patients (38.6%), with 25 of these operations performed after 2017. Patients treated in 2017-2019 were significantly more able to take thin liquid (P < 0.001) and lost less weight (P = 0.015) compared to those treated in 2005-2016. Multivariate analysis of 61 patients who did not undergo laryngeal suspension and/or cricopharyngeal myotomy showed significant feeding tube dependency in those aged 65 years and older (P = 0.004). Thin liquid intake was significantly improved after subtotal glossectomy with laryngeal suspension, which led to better postoperative swallowing and improved quality of life.

Clinical significance of intramedullary Gd-DTPA enhancement in cervical myelopathy.

STUDY DESIGN: Prospective multicenter study. OBJECTIVE: To clarify the significance of intramedullary Gd-DTPA enhancement in cervical myelopathy, the prevalence, morphologic features, clinical relevance and postoperative change were investigated. SETTING: Four hospitals in Japan. METHODS: A total of 683 patients with cervical myelopathy who underwent decompressive surgery were consecutively examined. T1, 2 and Gd-DTPA-enhanced MRI were taken before surgery. Fifty consecutive cases without intramedullary enhancement were allocated in the non-enhancement group. The following variables were investigated: prevalence of the enhancement, the morphologic feature, the relationship between the enhancement and T2 high-intensity areas, the change of the Japanese Orthopedic Association (JOA) score for cervical myelopathy and the change of the enhancement after surgery. RESULTS: Intramedullary enhancement was observed in 50 cases (7.3%). The enhancements were observed between the most severely compressed disc and the cranial half of the lower vertebral body. On axial images, they were observed at the posterior or posterolateral periphery of the spinal cord. Enhancement areas were observed within T2 high-intensity areas and smaller than them. The preoperative JOA score was 9.8+/-2.8 points in the enhancement group and 9.8+/-3.3 points in the non-enhancement group (NS). The postoperative JOA score was 12.7+/-2.9 points in the enhancement group and 14.2+/-2.4 in the non-enhancement group (P=0.006). Intramedullary enhancement disappeared in 60% of the patients 1 year after surgery. CONCLUSION: Intramedullary enhancement indicated not the severity of preoperative symptoms, but a sign of a worse prognosis.

Nasal immunization with Porphyromonas gingivalis outer membrane protein decreases P. gingivalis-induced atherosclerosis and inflammation in spontaneously hyperlipidemic mice.

Porphyromonas gingivalis has been shown to accelerate atherosclerotic lesion development in hyperlipidemic animals. We assessed the potential of a nasal vaccine against P. gingivalis infection for the prevention of atherosclerosis. Apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice were nasally immunized with the 40-kDa outer membrane protein (OMP) of P. gingivalis plus cholera toxin (CT) as adjuvant and then challenged intravenously with P. gingivalis strain 381. The animals were euthanized 11 or 14 weeks later. Atheromatous lesions in the proximal aorta of each animal were analyzed histomorphometrically, and the serum concentrations of 40-kDa OMP-specific antibodies and cytokines were determined. The areas of the aortic sinus that were covered with atherosclerotic plaque and the serum levels of inflammatory cytokines and chemokines were increased in Apoe(shl) mice challenged with P. gingivalis compared to nonchallenged mice. In comparison, nasal immunization with 40-kDa OMP plus CT significantly reduced atherosclerotic plaque accumulation in the aortic sinus and lowered the serum levels of cytokines and chemokines compared to nonimmunized animals. Nasal immunization also induced 40-kDa OMP-specific serum immunoglobulin G (IgG) and saliva IgA antibody responses. These findings suggest that systemic infection with P. gingivalis accelerates atherosclerosis in Apoe(shl) mice, and 40-kDa OMP plus CT may be an effective nasal vaccine for the reduction of atherosclerosis accelerated by P. gingivalis in the hyperlipidemic mouse model.

Increased Facet Fluid Predicts Dynamic Changes in the Dural Sac Size on Axial-Loaded MRI in Patients with Lumbar Spinal Canal Stenosis.

BACKGROUND AND PURPOSE: Axial-loaded MR imaging, which simulates the spinal canal in a standing position, demonstrates reductions of the dural sac cross-sectional area in patients with lumbar spinal canal stenosis. However, there has been no useful conventional MR imaging finding for predicting a reduction in the dural sac cross-sectional area on axial-loaded MR imaging. Previous studies have shown that increased facet fluid is associated with the spinal instability detected during positional changes. The purpose of this study was to analyze the correlations between facet fluid and dynamic changes in the dural sac cross-sectional area on axial-loaded MR imaging. MATERIALS AND METHODS: In 93 patients with lumbar spinal canal stenosis, the dural sac cross-sectional area was measured by using axial images of conventional and axial-loaded MR imaging. Changes in the dural sac cross-sectional area induced by axial loading were calculated. The correlation between the facet fluid width measured on conventional MR imaging and the change in dural sac cross-sectional area was analyzed. The change in the dural sac cross-sectional area was compared between the intervertebral levels with and without the facet fluid width that was over the cutoff value determined in this study. RESULTS: The dural sac cross-sectional area was significantly smaller on axial-loaded MR imaging than on conventional MR imaging. The facet fluid width significantly correlated with the change in the dural sac cross-sectional area (r = 0.73, P < .001). The change in the dural sac cross-sectional area at the intervertebral level with the facet fluid width over the cutoff value was significantly greater than that at the other level. CONCLUSIONS: The increased facet fluid on conventional MR imaging is highly predictive of the dynamic reduction of dural sac cross-sectional area detected on axial-loaded MR imaging in the clinical assessment of lumbar spinal canal stenosis.

Potentiated maturation with a high proliferating activity of acute promyelocytic leukemia induced in vitro by granulocyte or granulocyte/macrophage colony-stimulating factors in combination with all-trans retinoic acid.

All-trans retinoic acid (ATRA) induces differentiation of acute promyelocytic leukemia (APL), but the effect of cytokines regulating myeloid differentiation on ATRA-induced APL cells is poorly understood. In this study, maturation and proliferation of fresh APL cells were examined when induced in vitro by granulocyte or granulocyte/macrophage colony-stimulating factors (G-CSF or GM-CSF) in combination with ATRA. APL cells showed a low proliferating activity when induced by ATRA alone. In contrast, cells induced by G-CSF or GM-CSF alone showed increased DNA syntheses, the levels of which were not significantly affected by the combination of ATRA with CSFs. Interestingly, G-CSF or GM-CSF potentiated the capability of ATRA-induced cells to reduce nitroblue tetrazolium (NBT), while G-CSF or GM-CSF alone induced no NBT reduction. Furthermore, in several patients examined, APL cells induced by ATRA with G-CSF showed an increased activity of chemotaxis and CD11a expression. These findings suggest that G-CSF or GM-CSF can potentiate differentiation of ATRA-induced APL cells while stimulating their proliferating activity as well, and that G-CSF, rather than GM-CSF, may be a useful adjunct to promote ATRA-induced differentiation of APL.

Changes in DNA copy number in primary gastric carcinomas by comparative genomic hybridization.

We examined 33 primary gastric carcinomas using comparative genomic hybridization to detect changes in the DNA copy number and the chromosomal location of these changes. Ninety-four percent (31 of 33) showed 1 or more DNA copy number changes, such as increases at 2p23-p25 (observed in 21% of the total cases), 3q26.3-q27 (24%), 7p15 (24%), 9p22-pter (18%), and 13q22-q34 (21%) and decreases at 1p34.2-p36.2 (18%) and Y (52%). Histological examination indicated that increases at 3q26.1-q26.3 and 7p15 and decreases at 1p36.1-p36. 2 and Y were commonly observed in both differentiated and undifferentiated types. Increases at 3q27, 6q23-q25, and 7cen-p14 and decreases at 1p34.2-p35 and 17p12 were predominantly observed in the differentiated type, and increases at 2p23-pter, 9p22-pter, and 13q31-qter and a decrease at 6p21.3 were predominantly observed in the undifferentiated type. In addition, clinical staging of tumors showed that increases at 2p23-p25, 7p14-p21, 7q31-q32, and 9p22-pter and a decrease at Y were observed in early-stage tumors, whereas increases at 9q32-q33 and 15q26 were observed only in late-stage tumors. Many of the abnormalities detected in this study were not previously reported in gastric carcinomas. Our comparative genomic hybridization results indicate the presence of genetic alterations that may play some important role in the development and progression of gastric carcinomas.

Effects of antithyroid drug therapy on blood glucose, serum insulin, and insulin binding to red blood cells in hyperthyroid patients of different ages.

The mechanism of glucose intolerance in thyrotoxicosis was investigated in 119 patients with Graves's disease with careful consideration of the age-related deterioration of glucose tolerance. Before and after treatment of thyrotoxicosis with antithyroid drug, changes of blood glucose (BG) and serum immunoreactive insulin (IRI) in response to 50 g oral glucose tolerance test (OGTT) and insulin binding to red blood cell (RBC) were evaluated. In control subjects, the sigma IRI/sigma BG ratio after 50-g OGTT decreased progressively with age without significant change in absolute sigma IRI value, suggesting the occurrence of age-related insulin resistance. Glucose intolerance was much more apparent in hyperthyroid patients because of age-related relative decrease of insulin secretion. Such a decrease of insulin secretion was not found in age-matched postgastrectomy patients with a similar degree of hyperglycemia, however. Maximal binding of labeled insulin and number of insulin receptors of RBC were decreased in old patients but binding affinity was unchanged. Elevation of BG was partially suppressed when serum thyroxine (T4) and triiodothyronine (T3) were reduced to moderately supernormal levels, whereas sigma BG, sigma IRI, sigma IRI/sigma BG ratio, and insulin binding to RBC were all returned to normal when normal serum thyroid hormone concentration was maintained. Our data indicate that insufficient insulin secretion and reduced insulin action at the target cell are responsible, at least in large part, for age-related glucose intolerance in hyperthyroid patients.

Solubilization, purification, and partial characterization of thyrotropin receptor from bovine and human thyroid glands.

In an attempt to purify the thyroid receptor for TSH and to study interaction with the thyroid-stimulating antibody (TSAb) of graves' disease, we used both bovine and human thyroid glands. With either tissue, the 10,000 X g pellet of homogenized material was solubilized with 0.5% Triton N-101; excess Triton was removed by Amberlite XAD-2, and purification was effected by TSH affinity chromatography, followed by gel filtration on Sepharose 6B. Greatest purification was achieved with bovine tissue; this receptor preparation was 183-fold concentrated over the starting material, but contained only 6% of the original TSH-binding activity, due in part to spontaneous loss over the 4 days required for processing. On polyacrylamide gel electrophoresis, there were at least three protein bands, one of which was probably a subunit of thyroglobulin. Purified immunoglobulin G with thyroid-stimulating antibody activity inhibited the binding of TSH at all stages of purification of the receptor.

Transient neonatal hypothyroidism due to maternal immunoglobulins that inhibit thyrotropin-binding and post-receptor processes.

Transient neonatal hypothyroidism was found in a daughter of a 25-yr-old mother, who was receiving treatment for primary hypothyroidism due to Hashimoto's thyroiditis. During the neonatal period the infant had antithyroid microsomal and antithyroglobulin antibodies and TSH-receptor antibodies. The daughter recovered spontaneously from the hypothyroid state and the antithyroid antibodies disappeared from her serum. The mother's serum contained the same antibodies, and immunoglobulin G (IgG) from maternal serum blocked TSH binding to its receptors, TSH-stimulated cAMP responses, and cAMP-stimulated iodine uptake and organification in cultured thyroid cells. The latter finding suggests that the IgG had a postreceptor locus of action as well as inhibiting TSH binding to its receptor. The presence of such IgGs might have induced hypothyroidism both in the mother and in the daughter.

Pituitary-thyroid feedback regulation in patients with Graves' disease during antithyroid drug therapy.

In an attempt to study the mode of normalization of thyroid function in patients with Graves' disease, a study was made on 140 patients with Graves' disease who were eumetabolic after appropriate therapy with antithyroid drugs for more than 9 months. T3 administration failed to suppress thyroidal radioiodine uptake and serum T4 in patients with TRH-unresponsive TSH secretion. In addition, exogenous TSH failed to elevate serum levels of T4 and T3. In patients with TRH-responsive pituitaries, T3 administration uniformly made serum TSH undetectable but produced various effects (unsuppressible, partially suppressible, and suppressible) on radioiodine uptake and serum T4. The magnitude of suppression of radioiodine uptake paralleled that of serum T4. In patients with unsuppressible or partially suppressible thyroids, exogenous and endogenous TSH were less effective in elevating serum T4 and T3. In patients with suppressible thyroids, T3 administration depressed radioiodine uptake and serum T4; the magnitudes of depression were comparable to those found in normal subjects. Exogenous and endogenous TSH elevated serum T4 and T3 in patients with suppressible thyroids. Here again, the magnitudes of elevation were comparable to those found in the normal subjects. The serum T3 to T4 ratio was high before treatment, but decreased significantly during antithyroid drug therapy. The magnitude of decrease was roughly proportional to the degree of T3 suppressibility.

Studies of thyroid function and immune parameters in patients with hyperthyroid Graves' disease in remission.

The natural course of hyperthyroidism due to Graves' disease after discontinuation of antithyroid drug therapy was studied in 184 patients who had been treated with methimazole and whose thyroid function was suppressible with T3 when methimazole was discontinued. The patients were followed after discontinuation of therapy for up to 60 months. Serum T4, free T4 (FT4) and T3 levels, TSH receptor antibody (TRab) and anti-DNA antibody titers, and the percentage of HLA-DR positive lymphocytes in peripheral blood were measured serially. TRab and anti-DNA antibody tests were positive in the majority of patients before treatment and were negative in most at the end of treatment. Twenty-three (12.5%) patients had a recurrence of their hyperthyroidism, which occurred a mean of 20 months after withdrawal of methimazole; they are designated as having overt recurrent hyperthyroidism (group A). In these patients, serum T4, FT4 and T3 concentrations increased rather abruptly to markedly elevated levels in a several-month period and the TRab and anti-DNA antibody titers increased markedly at or shortly after recurrence in the majority. In 9 patients (4.1%), TRH-induced TSH secretion became totally suppressed, indicating the reappearance of thyroidal autonomy; however, the patients did not have any hyperthyroid signs and symptoms (subclinical hyperthyroidism; group B). Their serum T4 and FT4 concentrations fluctuated in the upper normal to slightly supra-normal range, and their serum T3 concentrations remained within the normal range throughout the follow-up period, but their TRab and anti-DNA antibody titers did not appreciably increase. Thus, the time of recurrence could not be precisely determined in group B. In the remainder (152 patients; 83.4%), serum thyroid hormone levels and TRH-induced TSH secretion remained normal, TRab and anti-DNA antibody titers remained negative, and hyperthyroidism did not recur (euthyroid remission; group C). At the time of final examination (in groups B and C) or at the time of recurrence (in group A), the percentage of HLA-DR positive peripheral lymphocytes was 17.9% in group A, 15.9% in group B, and 12.1% in group C. Retrospective analysis of the data indicated that the mean pretreatment TRab titer (percent inhibition of TSH binding) was slightly but not significantly lower in group C (37.8%) compared to those in group A (53.9%) and group B (54.8%). The 3 groups were indistinguishable by all other laboratory data both before treatment and at the time of the T3 suppression test. These data strongly indicate heterogeneity among patients with hyperthyroidism due to Graves' disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Difference in pituitary-thyroid feedback regulation in hypothyroid patients, depending on the severity of hypothyroidism.

In an attempt to study pituitary-thyroid interplay during replacement therapy for hypothyroidism, T4 (75-150 micrograms/day) was administered for at least 3 months. A small dose of T4 (75 micrograms/day) significantly depressed basal and TRH-stimulated TSH levels in normal subjects without significantly elevating serum T4 and T3 concentrations. In patients with severe hypothyroidism and marked enlargement of the sella turcica, T4 (2.53 micrograms/kg BW) normalized the serum T4 and slightly elevated the serum T3 but failed to normalize basal and TRH-stimulated TSH levels. In patients with moderate hypothyroidism and moderate enlargement of the sella turcica, T4 (2.0 micrograms/kg BW) normalized serum T4, T3, and basal TSH concentrations but failed to normalize TRH-stimulated TSH levels. In patients with slight hypothyroidism and slight enlargement of the sella turcica, T4 (1.84 micrograms/kg BW) normalized serum T4, T3, and TSH (both basal and TRH stimulated) concentrations. In five patients, an apparent paradoxical increase of basal serum TSH level was found shortly after starting thyroid hormone treatment. It is suggested that pituitary-thyroid interplay during the first 3-6 months of replacement therapy for hypothyroidism varies greatly depending on the severity of hypothyroidism.

Reappraisal of the 3,5,3'-triiodothyronine-suppression test in the prediction of long term outcome of antithyroid drug therapy in patients with hyperthyroid Graves' disease.

Thyroidal suppressibility by exogenous T3 in terms of both radioiodine uptake (RAIU) and serum T4 was evaluated in 115 hyperthyroid patients treated with methimazole for 2 yr and followed for an additional 2 yr to study the rate of recurrence. Various other serum parameters including serum thyroglobulin concentrations, thyroid autoantibody, and TSH receptor antibody titers, and thyroidal responses to TRH-induced TSH elevation were also determined. After 2 yr of methimazole therapy, thyroidal RAIU was not suppressible (RAIU less than 12%/4 h was defined as suppressible) in 50 of 115 patients (group I). Of 65 patients with suppressible thyroid RAIU, serum T4 was significantly reduced (less than 60% of pre-T3 level) by T3 administration in only 43 patients (group III) but not in the remainder (group II). Antithyroid drug therapy was discontinued in the group II and III patients, and 7 of the patients had recurrence of hyperthyroidism within 2 yr of follow-up. All of them were from group II. The thyroidal response to TSH was greater in group III patients than in group II patients. During antithyroid drug therapy, decrease of microsomal antibody titer was more likely to occur in group III patients than in those of group II. Serum thyroglobulin concentrations were uniformly normal in treated patients irrespective of T3 suppressibility. TSH receptor antibody was positive in all 13 untreated patients with Graves' disease but was negative in treated patients regardless of their T3 suppressibility. Measurement of both thyroidal RAIU and serum T4 after administration of T3 improves the reliability of T3-suppression testing as a predictor of the remission of Graves' disease.

Black (or brown) adrenal cortical adenoma: its characteristic features on computed tomography and endocrine data.

Seventeen patients with adrenal adenoma causing Cushing's syndrome, eight patients with Cushing's disease due to hypersecretion of ACTH, and five patients with primary aldosteronism due to an aldosteronoma were studied for their computed tomographic (CT) patterns, hormonal profiles, and macroscopic and microscopic findings of the adrenal gland. Black (or brown) adrenal adenomas were found in 71% of the patients with Cushing's syndrome, but not in patients with aldosteronoma. The adrenal tissue of patients with Cushing's disease was predominantly yellow. The number of compact cells was larger in black or brown adenomas than in yellow tumors or hyperplastic adrenal tissue. In patients with Cushing's syndrome, urinary excretion of 17-ketosteroids (17-KS) and serum aldosterone concentrations were lower in those with black or brown adenomas than in those with yellow adenomas (P less than 0.05). Patients with Cushing's disease had even higher 17-KS and serum aldosterone levels. No difference was found in serum cortisol concentrations and dexamethasone suppressibility in two types of adenomas causing Cushing's syndrome. Visual estimation of radiological density of the adrenal tissue relative to the kidney on CT scan and quantitative measurement of it by CT number revealed a difference between the two types of adrenal tumors causing Cushing's syndrome. Adrenal tumors with decreased density on CT scan were yellow adenomas with predominantly clear cells, and those with equal or increased density were black or brown adenomas with predominantly compact cells. All aldosteronomas had decreased density and consisted of clear cells. It is suggested that black or brown adenomas of the adrenal gland have higher radiological density and accompanying lower serum aldosterone and urinary 17-KS levels than ordinary yellow tumors. The abundance of compact cells may have some significance for the development of this particular type of adrenal tumor.

Concurrent hypersecretion of aldosterone and cortisol from the adrenal cortical adenoma.

Hypertension, hypokalemia, suppressed plasma renin activity and increased plasma aldosterone were found in a middle-aged woman. Following removal of the tumor in the left adrenal gland these abnormalities disappeared. Concurrently, however, the plasma cortisol level did not show normal diurnal change, although the value at 6 A.M. was within the normal range. Administration of 2 mg dexamethasone failed to depress the plasma cortisol level and urinary 17-OHCS concentrations. Postoperatively, plasma cortisol and urinary 17-OHCS were below normal. Histologic examination of the tumor indicated the presence of two types of adenoma cells; one was a large watery clear cell with rich lipid and possibly with aldosterone secretion and the other was an acidophilic cell with poor lipid and possibly with cortisol secretion. It is suggested that, in addition to oversecretion of aldosterone, the tumor autonomously secreted cortisol, although the amount of cortisol secreted was not large enough to produce typical Cushing's syndrome.

Serum thyroglobulin concentration as an indicator for assessing thyroid stimulation in patients with Graves' disease during antithyroid drug therapy.

PURPOSE: The purpose of this study was to elucidate the mechanism of regulation of serum thyroglobulin concentration in patients with Graves' disease and to establish the clinical usefulness of this measurement. PATIENTS AND METHODS: Serum thyroglobulin concentration was analyzed in relation to serum thyrotropin receptor antibody (TRab) titer and thyrotropin concentration in 166 patients with Graves' disease without thyroglobulin antibody. RESULTS: A total of 113 patients were treated and had been kept euthyroid for at least 10 months with methimazole and underwent a triiodothyronine (T3) suppression test. At the time of the T3 suppression test, the serum thyroglobulin concentration (ng/mL) was 33 +/- 31 in 80 of them with T3-suppressible (radioiodine uptake less than 12%) thyroids, negative TRab titers (less than 15% displacement), and normal serum thyrotropin concentrations (0.1 to 3.0 mU/L). Patients with T3-non-suppressible thyroids were divided into three subgroups according to serum TRab titers and thyrotropin concentrations: those with a negative TRab titer and a normal serum thyrotropin concentration (n = 9), those with a positive TRab titer and a normal thyrotropin concentration (n = 18), and those with a positive TRab titer and undetectable thyrotropin (n = 6). Serum thyroglobulin concentrations (ng/mL) were 116 +/- 40 in the first group, 249 +/- 194 in the second group, and 399 +/- 205 in the third group. In the other 39 methimazole-treated patients, 72 determinations of serum thyroglobulin concentration were performed either before or during treatment without the T3 suppression test, and it correlated well with the TRab titer but not with the serum thyrotropin concentration. In 14 patients who became hypothyroid due to excess methimazole, the serum thyroglobulin concentration increased concurrently with elevation of the serum thyrotropin concentration and normalized during thyroxine supplementation. In treated patients with T3-suppressible thyroids, the serum thyroglobulin concentration was similar among those with positive (n = 54) and negative (n = 26) microsomal antibody, indicating that the presence of Hashimoto's thyroiditis does not profoundly affect the serum thyroglobulin level. Among 80 patients with T3-suppressible thyroids who were followed without methimazole for a mean period of 31.1 months, eight (10%) experienced a clinically overt recurrence of hyperthyroidism. Serum thyroglobulin concentration and TRab titer (%) in these eight patients were 188.1 +/- 101.7 and 27.8 +/- 12.6, respectively. Thyroglobulin and TRab did not increase in the patients who remained euthyroid (n = 71) or who experienced subclinical recurrence (n = 1). CONCLUSIONS: Abnormal thyroid stimulator(s) and thyrotropin synergistically (if both are present in the serum) or independently (if either one is present) stimulate thyroglobulin secretion in patients with Graves' disease. Therefore, serum thyroglobulin concentration can be a useful means of assessing the degree of thyroidal stimulation and, if serum thyrotropin is normal or suppressed, correlates well with thyroidal stimulation even in patients with a negative TRab titer.

Rapid and wide-reaching delivery of HIV-1 env DNA vaccine by intranasal administration.

Although the potential of DNA vaccination is now beginning to be greatly appreciated, no detailed study of its localization in tissue or its expression kinetics has been reported. In this study, we investigated these issues using HIV-1 DNA plasmids administered either intranasally or intramuscularly. Fluorescence in situ hybridization (FISH) revealed that the human immunodeficiency virus (HIV) plasmids administered intranasally localized in the alveoli, lung, liver, spleen, regional lymph nodes, kidney, fetus, and esophagus. These HIV plasmids were detected 2 to 4 weeks after administration. We detected messenger RNA production of HIV env gene in the lung, liver and spleen, and human immunodeficiency virus type 1 (HIV-1)-specific proteins were detectable in the lung. These observations may provide important information for understanding the mechanisms of strong immune activation induced by DNA vaccination via the intranasal route. This technology of DNA administration suggests possible practical applications for vaccination and probably for gene therapy.

Aberrant progenitors common to megakaryocytic and myeloid cells in a Down's infant with transient abnormal myelopoiesis.

Phenotypic characteristics of blasts were studied in a Down's infant with transient abnormal myelopoiesis (TAM). Two major subpopulations were identified: (1) CD33+CD42b+ cells with platelet peroxidase activity, the commitment of which to megakaryocytic lineage was supported by an increased expression of GATA-1 mRNA; (2) CD33+CD34+CD7+CD4+ cells with immature ultrastructure, which could be either immature megakaryocytic or myeloid cells with aberrant differentiation. Mixed colonies containing megakaryocytes and monocyte/macrophages in the peripheral blood suggested the presence of progenitors common to these subpopulations. These results may indicate that subpopulations of blasts with phenotypic diversity could be derived from aberrant common progenitors to megakaryocytic and myeloid lineages in this patient.

Infection density of Wolbachia and incompatibility level in two planthopper species, Laodelphax striatellus and Sogatella furcifera.

Wolbachia, a bacterial endosymbiote of arthropods, causes cytoplasmic incompatibility (CI) in many insect species. CI traits were studied in two planthopper species, Laodelphax striatellus and Sogatella furcifera, and Wolbachia densities in these planthopper species were calculated by quantitative PCR methods. The CI level of L. striatellus was quite high and even aged males strongly caused CI. In contrast, S. furcifera showed partial CI, and males lost their ability to cause CI with age. Wolbachia infecting these two planthopper species were the same with respect to the nucleotide sequences of Wolbachia genes, 16S rDNA, ftsZ gene, groE genes, and wsp gene. Two methods for quantitative PCR, one using a DNA sequencer and the other a real-time sequence detection system, were established to calculate the amount of Wolbachia in the planthoppers. The density of Wolbachia in S. furcifera males was quite low. The difference in CI levels between the two planthopper species seems to be due to different amounts of Wolbachia infecting males.

Effect of normalization of hypometabolic state on blood pressure in spontaneously hypertensive rats and in patients with essential hypertension.

Spontaneously hypertensive rats (SHR) manifest a hypothyroid state as evidenced by increased thyroid weight, an increased level of plasma thyroid-stimulating hormone (TSH) and a decreased level of plasma thyroxine (T4) and triiodothyronine (T3). In 18 patients with essential hypertension, plasma TSH, T4 and T3 concentrations were all within the normal range, but the T4 level was significantly lower than in the controls. Among 21 hypothyroid patients, 2 had essential hypertension. Administration of thyroid hormone brought the metabolic state to normal in SHR and in hypothyroid patients but failed to affect the blood pressure. It is suggested that abnormality of thyroid function is neither the cause nor the accentuating factor in the development of hypertension in SH rats and in man.