New Approach for Exploring Cerebral Functional Connectivity: Review of Cortico-cortical Evoked Potential

There has been a paradigm shift in the understanding of brain function. The intrinsic architecture of neuronal connections forms a key component of the cortical organization in our brain. Many imaging studies, such as noninvasive magnetic resonance imaging (MRI) studies, have now enabled visualization of the white matter fiber tracts interconnecting the functional cortical areas in the living brain. Although such a structural connectome is essential for understanding of cortical function, the anatomical information alone is not sufficient. Practically, few techniques allow the investigation of the excitatory and inhibitory mechanisms of the cortex in vivo in humans. Several attempts have been made to track neuronal connectivity by applying direct electrical stimuli to the brain in order to stimulate subdural and/or depth electrodes and record responses from the functionally connected cortex. In vivo single-pulse electrical stimulation (SPES) and/or cortico-cortical evoked potential (CCEP) were recently introduced to track various brain networks. This article reviews the concepts, significance, methods, mechanisms, limitations, and clinical applications of CCEP in the analysis of these dynamic connections.     

Analysis of Met235 to Thr variant of the angiotensinogen gene in relation to the blood pressure and family history of essential hypertension in Japanese children

A recent study reported a significant relationship between a T⁷⁰⁴→C (Met²³⁵→Thr) variant in exon 2 of the angiotensinogen gene in adults and essential hypertension. In the present study, this variant was detected in 131 Japanese children using a polymerase chain reaction. The allele frequency of the variant was 0.76. The genotype frequency of the homozygote for the allele was 0.59, and children who were homozygous had higher systolic blood pressure than those with the other two genotypes. No relationship was found between children's polymorphism and a family history of essential hypertension. These findings suggest that this molecular variant of the angiotensinogen gene may play some role in the regulation of blood pressure in Japanese children.     

Distribution of human herpesvirus 6 and varicella-zoster virus in organs of a fatal case with exanthem subitum and varicella

The distribution of human herpesvirus 6 (HHV-6) and varicella-zoster virus (VZV) was examined in autopsy samples from a fatal case with both virus infections. A 9-month-old boy developed convulsive seizures followed by macular skin rashes, rapidly progressed to brain death, and died 15 days after the onset, when signs of varicella were noted. An isolation of HHV-6 from blood and evaluation of antibody activities to various viral agents including HHV-6 were performed before his death. Postmortem examinations included: (i) isolation of HHV-6 and VZV from tissues or organs; (ii) detection of both virus antigens in tissues or organs by an indirect immunofluorescent assay using monoclonal antibodies to both viruses; (iii) amplification of both viruses and human herpesvirus 7 DNA sequences by a nested polymerase chain reaction assay; and (iv) endonuclease digestion of amplified products of HHV-6 DNA for differentation of variants A and B. Human herpesvirus 6 DNA was detected in peripheral blood mononuclear cells (PBMC) and plasma obtained at the eruptive stage but present only in PBMC 15 days after, indicating the primary infection with HHV-6, although the virus was not isolated from the same blood sample and a significant rise in the antibody titers to HHV-6 was not observed. Both virus antigens and DNA were detected in various tissues or organs obtained at autopsy, but only VZV was isolated from these samples, suggesting disseminated infection with both viruses in an infant. All the amplified products of HHV-6 DNA were variant B. Among the findings for the distribution of virus antigens, it was noteworthy that HHV-6 antigen was demonstrated in the endothelial cells of small vessels in the frontal lobe of the brain. There was no evidence of HHV-7 infection. These data indicate that the primary HHV-6 infection closely followed by the primary VZV infection had the potential hazard of an unexpected and apparently life-threatening event, in which disseminated infections with both viruses were noted in multiple tissues or organs including the brain.     

Change of renal function during vancomycin therapy in extremely low birthweight infants

Twenty extremely low birthweight infants were treated with vancomycin (VCM). Their gestational age was 26.3 ± 1.4 weeks (range 24.0–28.7 weeks) and their birthweight was 829 ± 133 g (range 562–990 g). At the time of initial administration of VCM, postnatal age was 29.5 ± 15.8 days (range 5–54 days). Vancomycin was administered in a dose between 9.3 and 11.0 mg/kg every 12 h for a period of 6.3 ± 2.4 days (range 4–13 days). Serum and urinary specimens were obtained before and after (within 24 h following the last dose) VCM therapy. Serum creatinine and sodium, and urinary N-acetyl-β-D-glucosaminidase (NAG) activity, creatinine, sodium, and β-2-microglobulin (BMG) concentrations were measured. Fractional excretion of sodium (FENa) and NAG index (NAG: creatinine ratio) were calculated. There were no significant differences between the before and after VCM treatment in serum creatinine, urinary BMG concentration, FENa and NAG index. No infant showed any symptoms of renal insufficiency. However, the NAG index and FENa increased after treatment in 1 of 20 infants. Vancomycin is effective and safe in the treatment of serious infections in extremely low birthweight infants.     

Serum level and gene polymorphism of angiotensin I converting enzyme in Japanese children

The aim of the present study was to determine the distribution of the insertion/deletion polymorphism of angiotensin I converting enzyme (ACE) gene in Japanese children. In addition, the relationship between this polymorphism and serum ACE levels in the same population were analyzed. Insertion/deletion polymorphism located in intron 16 of the ACE gene was examined by polymerase chain reaction in Japanese children aged 10–15 years. Allele frequencies were 0.64 for the insertion allele and 0.36 for the deletion allele in 122 subjects. No association was found between genotypes in this polymorphism and the level of systolic or diastolic blood pressure. A significant relationship between this polymorphism and serum ACE activity was observed. These results suggest that interindividual variability of serum ACE level is strongly influenced by the ACE genotype as early as in childhood.     

Congenital hypothyroidism with delayed rise in serum TSH missed on newborn screening

We report on a female patient with congenital hypothyroidism (CH) missed on a newborn screening test. She is now 10 years old with retarded development. The patient was born premature at 34 weeks of gestation with birth-weight of 1515 g, and was judged to be normal in the screening programme of Niigata Prefecture. However, she gradually suffered from poor weight gain and retarded development with stridor at breathing. Serum thyroid stimulating hormone (TSH) levels were rechecked and showed high values with normal T3 and T4 levels. She was referred to our hospital at the age of 13 months. She was diagnosed as having CH (ectopic thyroid) with a delayed rise in blood TSH concentration, probably due to the prematurity of the hypothalamic-pituitary-thyroid axis. l -thyroxine therapy brought a decline in TSH levels with partial improvement of her symptoms. Regardless of the result of newborn screening, infants with elevated serum TSH levels should be carefully examined for possible CH, even when T3, T4 and free T4 values are in the normal range.     

Correspondence: Communication between the superior cervical sympathetic ganglion and the inferior laryngeal nerve

Complex arborisations occurs between the inferior ganglion of the vagus nerve and the superior cervical sympathetic ganglion (Braeucker, 1923; Fick, 1926; Siwe, 1931; Hoffman, 1957). The superior cervical sympathetic ganglion sends branches to the internal and the external carotid arteries, the inferior vagal ganglion, the superior laryngeal nerve and the cervical nerves, and provides superior cardiac and thyroid branches as well as the trunk that descends directly to the middle and inferior cervical sympathetic ganglia. There are communications between the vagus nerve (laryngeal branches) and the superior cervical sympathetic ganglion (SCSG). Cannizzaro et al. (1991) and Zerilli et al. (1994) reported abnormalities of sympathetic function among the effects of injury to the superior laryngeal nerve during thyroid surgery. The interconnections between these various nerves are therefore of clinical importance. We document here a rare example of complex communication between the vagus nerve and the SCSG in dissections of 113 adult (78 male, 35 female) Japanese cadavers. Both sides were examined in 88 cases, the right only in 18 and the left only in 7 (i.e. 201 sides in total).     

Expression of heat shock protein 47 is increased in remnant kidney and correlates with disease progression

Glomerulosclerosis is characterized by accumulation of the mesangial extracellular matrix, including type I and IV collagen. The processing for the collagens in the glomeruli may play a critical role for development of glomerulosclerosis. We examined the expression of heat shock protein 47 (HSP47), a collagen-binding molecular chaperone in the progresive glomerulosclerosis model. Subtotally nephrectomized rats, unlike sham-operated rats, developed focal and segmental glomerulosclerosis. Immunological staining demonstrated an increased expression of HSP47 which paralleled the expression of type I and IV collagen in the glomeruli of the nephrectomized rats as the glomerulosclerosis developed. The mRNA levels encoding type I and type IV collagen and HSP47 were increased 3.4 fold, 3.6 fold and 2.8 fold, respectively, at week 7 after nephrectomy. By in situ hybridization, the expression of HSP47 mRNA was determined to be localized to the glomeruli with segmental sclerosis. These results suggest that HSP47 may play a central role in the process of extracellular matrix accumulation during the development of glomerulosclerosis.     

Trophoblast Antigens in Human Seminal Plasma

ABSTRACT: Secondary recurrent spontaneous (2°) aborters manifest persistent IgG, which show differential cytotoxicity patterns with lymphocytes from many donors. These are non-HLA-directed antibodies, which react allotypically with both trophoblast and lymphocytes. The antigens they recognize are designated trophoblast-lymphocyte crossreactive (TLX) antigens. Xenogeneic anti-TLX sera were studied with the use of enzyme-linked-immunosorbent (ELISA) and immunochemical assays to determine the TLX status of seminal plasma. The results showed 1) allotypic TLX antigens are present in seminal plasma; 2) seminal plasma TLX antigens may be membrane associated; 3) by immuno-blotting, the molecular weights of antigens reactive with TLX antisera are 15, 22, 28, 33 kD and a smear between 180 and 340 kd; 4) by isoelectric focusing, TLX antigens show pI 4.0, 5.35, 5.9, 6.5, 6.8, and 7.2. Allotypic seminal plasma TLX antigens may provide the antigenic stimuli for persistent maternal humoral immunity.