Multiplicity in type V adenylylcyclase: type V-a and type V-b

Type V mammalian adenylylcyclase cDNA was originally isolated from two animal species, the dog and rat. The amino acid sequences from the two species are highly homologous, but completely different in the putative N-terminal, cytoplasmic region. Northern blot analysis using oligonucleotide probes unique to either of the two clones has revealed that the two forms of type V adenylylcyclase mRNA, canine form (= type V-a) and rat form (= type V-b), are co-expressed as splicing variants in both species. Genomic Southern blot analysis has suggested that the two forms are the products of a single gene. When overexpressed, however, deletion of the N-terminal domain did not alter any biochemical properties. Thus multiple splicing variants with unique N-terminal amino acid sequences of type V adenylylcyclase can be generated from a single gene, however, biochemical properties of these variants may not be different.     

New mutation type in pseudohypoparathyroidism type Ia

Context The GNAS gene encodes the α‐subunit of the stimulatory G proteins, which play a crucial role in intracellular signal transduction of peptide and neurotransmitter receptors. Heterozygous inactivating maternally inherited mutations of GNAS (including translation initiation mutations, amino acid substitutions, nonsense mutations, splice site mutations and small insertions or deletions) lead to a phenotype in which Albright hereditary osteodystrophy is associated with pseudohypoparathyroidism type Ia. Objective We sought to identify the molecular defect in a patient who was thought to have PHP‐Ia. Methods and results The GNAS gene of a 5‐year‐old boy with brachydactily, mental retardation, pseudohypoparathyroidism and congenital hypothyroidism was investigated. We found a heterozygous inversion of exon 2 and part of intron 1 of de novo origin. Molecular studies of cDNA from blood RNA demonstrated that both the normal and the mutant variants were stable and that new splice‐sites were generated. Conclusion This report demonstrates the first evidence for an inversion at the GNAS gene responsible of pseudohypoparathyroidism type Ia.     

Platelet membrane fluidity in type IIA, type IIB and type IV hyperlipoproteinemia.

Fluorescence spectroscopy, a very sensitive index for measuring the biophysical properties of living cell systems, was used to examine the structural order of intact, resting, gel-filtered platelets from hyperlipidemic subjects (n = 48, 25-70 years) and normolipemic subjects (n = 34, 19-68 years). Fluorescence anisotropy (r[s]), which is inversely related to membrane fluidity, was estimated using 3 different fluorescent dyes, DPH, TMA-DPH, and 6-AS, known to label different regions of biological membranes. Increased membrane fluidity was observed in type IIB (n = 24, 36-62 yrs; r[s] = 0.0692 +/- 0.09) and type IV (n = 10, 33-57 yrs; r[s] = 0.058 +/- 0.006) hyperlipidemics in comparison to type IIA (n = 14, 25-70 yrs; r[s] = 0.086 +/- 0.019) and control subjects (n = 24, 28-68 yrs; r[s] = 0.079 +/- 0.012). The temperature dependency of r[s]-DPH values was significantly different (P less than 0.01) in platelets from type IIB and type IV patients compared to type IIA and control subjects of similar age. A significant positive correlation (P less than 0.005) between membrane fluidity and age was found only in healthy control subjects (n = 34, 19-68 yrs). Despite significant (P less than 0.01) differences in plasma lipid concentrations in hyperlipidemic patients and controls, significant ex vivo relations between membrane fluidity and lipoprotein concentrations, free fatty acid distribution, and increased age were found only in healthy control subjects. Plasma levels of thromboxane as well as serum selenium concentrations did not significantly differ between hypercholesterolemic, hypertriglyceridemic, and control subjects.     

Alternating type A and type B Wolff-Parkinson-White syndrome

A patient with W-P-W syndrome is presented who manifested both Type A and B configurations. The problems treating similar patients with resistant tachyarrhythmias are briefly discussed.     

Long-term course of type I-simulating type II-diabetes mellitus

In only few cases of primarily non- insulin-dependent diabetes mellitus after many years an absolute insulin dependency can develop. Within 5000 patients of a diabetic outpatient clinic in 2 years this happened in 21 patients. These patients offered a C-peptide-secretion after stimulation which was typical for an insulin dependent diabetes. The investigation of HLA-frequencies showed a marked increase of the DR 3 und DR 4 loci. These results demonstrate that obviously the genetically as type I characterized diabetes may appear clinically in the picture of type II-diabetes for many years. This must be taken in consideration in therapeutic or epidemiologic questions.     

Nigerian HIV type 2 subtype A and B from heterotypic HIV type 1 and HIV type 2 or monotypic HIV type 2 infections

The presence of HIV-2 in Nigeria has been confirmed serologically, but not genetically. To determine the frequency of HIV-2 infections and the dynamics between HIV-1 and HIV-2 in 35 of 36 Nigerian states, 420 blood samples were collected in 1999. Antibodies to HIV-1 and HIV-2 were detected by EIA and seroreactivity was confirmed with the INNO-LIA HIV Line Assay. The frequency of HIV-2 was 4.3% (18 of 420), with 3.8% (16 of 420) HIV-1 and HIV-2 (HIV-1/2) heterotypic and 0.5% (2 of 420) HIV-2 homotypic infections. The presence of HIV-2 subtype B in the two monotypic HIV-2 infections and subtype A in 11 (68.8%) of 16 HIV-1/2 dually seropositive samples was established by sequencing and phylogenetic analysis. HIV-2 subtype B viruses were not found in any of the HIV-1/2 dual infections, and HIV-2 subtype A strains were not identified in either of the two monotypic HIV-2 infections. Since our sample size was small and represented only convenience samples, larger randomized studies will be needed to better understand the dynamics of infection between HIV-1 and different HIV-2 subtypes and to determine whether significant biological differences exist among the HIV- 2 subtypes.     

'Sensing' the link between type 1 and type 2 diabetes

Obesity-associated insulin resistance is a core element of metabolic syndrome and type 2 diabetes (T2D). Notably, insulin resistance is also a feature of type 1 diabetes (T1D), where findings in the non-obese diabetic mouse model have implicated transient receptor potential vanilloid-1 (TRPV1+) sensory neurons in local islet inflammation and glucose metabolism. Here, we briefly review the role of TRPV1 in non-obese diabetic (NOD) T1D pathogenesis, highlighting commonalities that suggest TRPV1 may contribute to obesity and T2D as well. With the recently discovered importance of adipose infiltrating lymphocytes in the metabolic disturbances of obesity and T2D, sensory innervation of fat may thus play an analogous role to sensory neurons in the islet--modulating neuroendocrine homeostasis and inflammation. In such a scenario, TRPV1+ sensory nerves would provide the pathoaetiological link connecting the shared metabolic and immunologic features of type 1 diabetes and T2D.     

Pancreatic volume in type 1 und type 2 diabetes mellitus

We measured pancreatic volume (PV) using helical computed tomography (CT) in 26 patients with type 1 diabetes mellitus (DM), 29 patients with type 2 DM, and 22 healthy individuals. We also evaluated the relationship between PV and the body surface area (BSA), established the pancreatic volume index (PVI) by dividing PV by BSA to correct PV for the body build, and examined its relationships with the duration of illness, serum C-peptide immunoreactivity level (CPR), and serum immunoreactive trypsin level (IRT). BSA and PV were correlated significantly (p<0.0001, r=0.645) in healthy individuals, and they were correlated also in the diabetic patients, (p=0.0023, r=0.563 in type 1 DM; p=0.0346, r=0.392 in type 2 DM). PV was significantly smaller in the type 1 DM group than in the healthy group and type 2 DM group (p<0.001 for both). PVI was also significantly smaller in the type 1 DM group than in the healthy group and type 2 DM group p<0.001 for both). PVI and IRT were significantly correlated in both DM groups (p<0.0001, r=0.732 in type 1 DM; p=0.0469, r=0.731 in type 2 DM). PVI was not correlated with the duration of illness or CPR. Helical CT was useful for the measurement of the pancreatic volume, and the pancreatic volume was reduced particularly in the patients with type 1 DM. A strong correlation was observed between PV and exocrine pancreatic function in type 1 DM, but the correlation between PV and exocrine pancreatic function was weak in type 2 DM. Received: February 2001 / Accepted in revised form: July 2001     

Human herpesvirus type 6 and type 7 in transplant recipients

Recent years have witnessed a growing interest in the role of human herpesvirus (HHV) type 6 and type 7 as emerging pathogens or copathogens in transplant recipients. Both HHV-6 and HHV-7 belong to the beta-herpesvirus family and are closely related to another member of the family, cytomegalovirus. After the primary infection, these viruses remain latent in the human host and can reactivate after transplantation. Various clinical processes such as fever, rash, pneumonitis, encephalitis, hepatitis, and myelosuppression have been described in association with herpesvirus. Moreover, a growing body of evidence suggests that the major impact of HHV-6 and HHV-7 reactivation in transplantation is related to indirect effects, such as their association with cytomegalovirus disease, increased opportunistic infections, and graft dysfunction and rejection. The pathogenesis of HHV-6 and HHV-7 during the post-transplantation period, the methods used for their diagnosis, and the evaluation of antiviral drugs and strategies for their prevention and treatment are now the subject of extensive research.     

Osteoporosis among patients with type 1 and type 2 diabetes

Both diabetes and fractures are prevalent in adults. The relationship between diabetes and osteoporosis is complex and, although it has been investigated extensively, the subject remains controversial. While low bone mineral density (BMD) is consistently observed in type 1 diabetes, the relationship is less clear in type 2 diabetes, with some studies reporting modestly increased or unchanged BMD. Both type 1 and type 2 diabetes have been associated with a higher risk of fractures. Despite discrepancies between BMD and fracture rates, clinical trials uniformly support the fact that new bone formation and bone microarchitecture and, thus, bone quality, are altered in both types of diabetes. Although a causal association between diabetes and osteoporosis cannot be established on the basis of existing data, it is possible to conclude from many studies and from a better understanding of the physiopathology of diabetes that it can increase the risk of fractures through skeletal (decreased BMD and bone quality) and extraskeletal (increased risk of falls) factors. Even though osteoporosis screening or prophylactic treatment in all patients with type 1 and type 2 diabetes is not being recommended at present, such patient populations should be given general guidelines regarding calcium and vitamin D intakes, exercise and the avoidance of potential risk factors for osteoporosis. The extent of diagnostic and therapeutic interventions should be based on the individual's risk profile for fractures.     

Structural involvement in type 1 and type 2 diabetic nephropathy

Structural changes underlying diabetic nephropathy in Type 1 diabetes are prodominant in the glomerulus [thickening of glomerular basement membrane (GBM) and mesangial expansion], but also include arteriolar, tubular and interstitial lesions. The structural measure that correlates best with all renal functional parameters in Type 1 diabetes is mesangial fractional volume [Vv(mes/glom)], an estimate of mesangial expansion. Structural-functional relationships in Type 2 diabetes are much less known. These studies investigated renal structure in the early stages of nephropathy [microalbuminuria (MA)] in patients with Type 1 and Type 2 diabetes. Diabetic glomerulopathy was quite advanced in Type 1 diabetic patients with MA, and both Vv (mes/glom) and GBM width were increased as compared to normoalbuminuric (NA) patients when the albumin excretion rate (AER) was > 30 microgram/min. Serial renal biopsies were performed 5 years apart in 11 Type 1 diabetic patients to evaluate whether glomerular and interstitial lesions progress jointly. AER increased significantly in 5 years, while the glomerular filtration rate remained unchanged. All structural parameters were initially abnormal. Vv(mes/glom) and mean glomerular volume increased significantly, whereas GBM width and the interstitial volume fraction were unchanged. Moreover, the change in Vv (mes/glom) was correlated with the change in AER (r =0.64, p <0.05). Thus, at the disease stage during which some patients progress to MA or proteinuria, continuing mesangial expansion is the main variable, whereas further interstitial expansion does not occur. A large number of Type 2 patients were also studied. Early diabetic glomerulopathy was detected by electron microscopy in NA patients and found to be more advanced in those with MA and proteinuria. However, lesions were milder than in Type 1 diabetic patients, and there was considerable overlap between groups. Morphometric results by electron microscopy were similar to those by light microscopy, demonstrating the heterogeneity of renal structure in Type 2 diabetic patients. In fact, only 30% of MA patients had typical diabetic glomerulopathy, while 40% had more advanced tubulo-interstitial and/or vascular lesions and 30% had normal renal structure.     

Diagnosis and management of type I and type V hyperlipoproteinemia

Both type I and type V hyperlipoproteinemia are characterized by severe hypertriglyceridemia due to an increase in chylomicrons. Type I hyperlipoproteinemia is caused by a decisive abnormality of the lipoprotein lipase (LPL)- apolipoprotein C-II system, whereas the cause of type V hyperlipoproteinemia is more complicated and more closely related to acquired environmental factors. Since the relationship of hypertriglyceridemia with atherosclerosis is not as clear as that of hypercholesterolemia, and since type I and V hyperlipoproteinemia are relatively rare, few guidelines for their diagnosis and treatment have been established; however, type I and V hyperlipoproteinemia are clinically important as underlying disorders of acute pancreatitis, and appropriate management is necessary to prevent or treat such complications. Against such a background, here we propose guidelines primarily concerning the diagnosis and management of type I and V hyperlipoproteinemia in Japanese.     

Progression of proteinuria in type 1 and type 2 diabetes

A longitudinal study evaluating the time course of the transition from normal to microalbuminuria, and then on to macroalbuminuria, was made over a mean period of 7 years in a cohort of 52 patients with Type 1 diabetes and 61 patients with Type 2 diabetes. Transient episodes of micro- and macroalbuminuria were often observed before the ultimate development of persistent Albustix-positive proteinuria. The transition from normal to microalbuminuria and from micro- to macroalbuminuria was characterized by rises in renal albumin clearance accompanied by lesser rises in total proteinuria. Seven patients with Type 1 and 12 with Type 2 diabetes showed evidence of progression, the interval for the transition from normal to macroalbuminuria varying from 3 to 5 years. In Type 1 diabetic patients, the development of micro- and macroalbuminuria was associated with a decline in renal function and a rise in systolic blood pressure without a significant change in blood glucose control. In Type 2 diabetic patients, the development of microalbuminuria was associated with a small decline in renal function but no change in blood pressure or blood glucose control. It is concluded that the transition from normal to micro- and on to macroalbuminuria may be more rapid then previously reported and varies considerably among individuals.     

Unusual type of hypochromic anemia complicating billroth II type gastrectomy

Summary An unusual type of hypoferremic hypochromic anemia, after Billroth II type of gastric resection, is presented. The ferrokinetic studies indicate defective red blood cell re-utilization of iron. It is postulated that a small intestinal disease which complicated this type of surgery, like any other inflammatory reaction, was responsible for production of defective red cell reutilization of iron, and anemia. This defect was corrected after the second operative procedure—ie, Henley jejunal interposition.Supported in part by USPHS Grants CA 05462 and H 6374, and the Clinical Research Center, Thomas Jefferson University Hospital.The authors wish to thank Mr. William Burke and Miss Shirley Wilcher for their technical assistance, and Drs. Allan J. Erslev and Dhodanand Kowlessar for critical review of this paper.     

Human botulism (type F)—A rare type

An unusual presentation of type F botulism (one of the world's three reported outbreaks) is described. The diagnosis was complicated by the presence of pre-existing Adie's myotonlc pupil. There was also a history of self-inflicted small-caliber gunshot wound to the right brain 10 years before the onset of the botulism. Post-traumatic seizure disorder, also present in this patient, was under good control. No offending food was ever discerned, despite exhaustive study.     

Poliovirus type 1/type 3 antigenic hybrid virus constructed in vitro elicits type 1 and type 3 neutralizing antibodies in rabbits and monkeys.

Poliovirus exists as three stable serotypes (PV-1, PV-2, and PV-3). These viruses display three antigenic sites each, designated N-AgI, N-AgII, and N-AgIII. When mice are immunized with poliovirus, N-AgI is the major neutralization antigenic site for PV-3, whereas N-AgII and N-AgIII are immunodominant over N-AgI for PV-1. To study the relationship between structure and antigenicity, a hybrid virus was constructed in which N-AgI of PV-1 was replaced by N-AgI of PV-3. PV-3- and PV-1-specific antisera, including those elicited by PV-3 in primates, neutralized the hybrid virus. Injection of the hybrid virus into rabbits or into primates resulted in the production of antisera that neutralized both PV-1 and PV-3. The data show that sequence replacement at N-AgI of poliovirus is compatible with viral proliferation, an observation useful for the development of multivalent picornavirus vaccines.     

Hand function in people with type 1 and type 2 diabetes

International Journal of Diabetes in Developing Countries - Impaired hand function has a negative impact on occupational performance and activities of daily living among people with diabetes....     

A previously undescribed type of quadricuspid aortic valve: type H

The discovery is reported of a previously undescribed type of quadricuspid aortic valve, which was comprised of two equal-sized smaller cusps and two unequal-sized larger cusps. This was proposed as the eighth type of quadricuspid valve, type H. This anatomic variation is the only type of quadricuspid valve that could exist in theory, but has not been previously described. It would therefore, complete the morphological classification of this entity.