Variability of the glycoprotein G gene in clinical isolates of herpes simplex virus type 1.

Glycoprotein G (gG) of herpes simplex virus type 1 (HSV-1) has been used as a prototype antigen for HSV-1 type-specific serodiagnosis, but data on the sequence variability of the gene coding for this protein in wild-type strains are lacking. In this study, direct DNA sequencing of the gG-1 genes from PCR products was performed with clinical HSV-1 isolates from 11 subjects as well as with strains Syn 17(+), F, and KOS 321. The reference strains Syn 17(+) and F showed a high degree of conservation, while KOS 321 carried 13 missense mutations and, in addition, 12 silent mutations. Three clinical isolates showed mutations leading to amino acid alterations: one had a mutation of K(122) to N, which is a gG-1-to-gG-2 alteration; another contained all mutations which were observed in KOS 321 except two silent mutations; and the third isolate carried five missense mutations. Two clinical isolates as well as strain KOS 321 showed a mutation (F(111)-->V) within the epitope of a gG-1-reactive monoclonal antibody (MAb). When all viruses were tested for reactivity with the anti-gG-1 MAb, the three strains with the F(111)-->V mutation were found to be unreactive. Furthermore, gG-1 antibodies purified from sera from the two patients carrying strains mutated in this epitope were less reactive when they were tested by an HSV-1-infected-cell assay. Therefore, our finding that the sequence variability of the gG-1 gene also affects B-cell epitope regions of this protein in clinical isolates may have consequences for the use of this protein as a type-specific antigen for serodiagnosis.     

Different types of mucosal adaptation in the ileal reservoir after restorative proctocolectomy. A two-year follow-up study

A histomorphologic study of the pelvic pouch mucosa during the first two years of function was performed in 11 consecutive patients treated for ulcerative colitis. Two types of mucosal adaptation were delineated. Type A response (5 patients) showed stable slight atrophy, normal numbers of goblet cells, and numerous sulphated mucin positive cells. The frequency of mitoses was higher than in the normal ileum. The degree of acute and chronic inflammation was low and decreasing or stable. Dysplasia was never seen. Type B response (5 patients) comprised progressive, finally severe atrophy accompanied by increasing degree of acute inflammation. The number of mitoses was higher than in type A response. In two patients the number of goblet cells was moderately/severely decreased and epithelial atypia or low grade dysplasia occurred repeatedly. The response was regarded as indeterminate in one patient. The determination of the types of mucosal adaptation may help in the planning of the follow-up of these patients.     

Pulmonary embolism associated with the use of anabolic steroids

We present the case of a 56-year-old man with deep vein thrombosis (DVT) and pulmonary embolism (PE). He had been given intramuscular injections of testosterone and the anabolic-androgenic steroid nandrolone, due to a muscle injury, a total of three times prior to manifestation of the symptoms. An ultrasonographic examination of the right leg revealed a DVT and computed tomography of the pulmonary arteries showed PE. The thromboembolic episodes in this previously healthy patient were in all probability associated with intramuscular injections of testosterone and nandrolone, to which there is a clear correlation in time.     

Correlation between fluorescein flowmetry and laser Doppler flowmetry. A study in the intestine (ileoanal pouch) in man

A study was undertaken to compare two new methods of capillary blood flow measurement, namely fluorescein flowmetry (FF) and laser Doppler flowmetry (LDF). The blood flow was measured in a pelvic pouch during its construction and in the completed ileoanal anastomosis in 12 patients. There was a high correlation between the two methods (correlation coefficient, 0.78) (p less than 0.01) when the blood flow was measured in the pelvic pouch. The correlation coefficient between the two methods for the difference between the blood flow in the pelvic pouch at the site of the planned anastomosis when the pouch resided in the abdomen and that in the completed ileoanal anastomosis was r = 0.99 (n = 12, p less than 0.001); the reduction amounted to 25% as measured by FF and 27% as measured by LDF (n = 12, p less than 0.01). All ileoanal anastomoses healed perfectly, the lowest FF and LDF values being 0.004 density units/sec and 0.3 V, respectively. The results indicate that either method can be considered for measuring capillary blood flow.     

Glycosaminoglycan-binding ability is a feature of wild-type strains of herpes simplex virus type 1

Adaptation of some viruses to replication in cultured cells selects variants that due to alterations in the viral attachment proteins convert to using heparan sulfate (HS) as initial receptor. We report that the nucleotide sequence of herpes simplex virus type 1 (HSV-1) glycoprotein C (gC), a principal attachment component of the virus, remained unchanged during adaptation of wild-type strains to cultured cells. Likewise, amino acid residues critical for binding of gC to HS were conserved in viral strains that replicated in vivo in different human tissues. Moreover wild-type HSV-1 strains derived directly from clinical specimens were, similar to their cell culture propagated progeny viruses and common laboratory strains, sensitive to heparin and demonstrated impairment in their ability to infect HS/chondroitin sulfate deficient cells. These results demonstrate that the HS-binding ability is a feature of wild-type strains of HSV-1.     

Confirmed reinfection with SARS‐CoV‐2 during a pregnancy: A case report

Pregnancy might impact immunity after SARS‐CoV‐2 infection and/or vaccination. We describe the first case of reinfection with SARS‐CoV‐2 during a pregnancy. While the mother lacked detectable antibodies 2 months after the first infection, both mother and baby had IgG antibodies at delivery. Infection did not cause any adverse pregnancy outcome.     

Typing of Clinical Herpes Simplex Virus Type 1 and Type 2 Isolates with Monoclonal Antibodies

The purpose of this study was to evaluate the performance of a herpes simplex virus (HSV) type 1-specific anti-glycoprotein C-1 monoclonal antibody (MAb) and a type 2-specific anti-glycoprotein G-2 MAb for typing of 2,400 clinical HSV-1 isolates and 2,400 clinical HSV-2 isolates, respectively, using an enzyme immunoassay. The anti-HSV-1 MAb showed sensitivity and specificity of 100%, and the anti-HSV-2 MAb showed a sensitivity of 99.46% and 100% specificity, indicating that these MAbs are suitable for typing of clinical HSV isolates.     

Conservation of type-specific B-cell epitopes of glycoprotein G in clinical herpes simplex virus type 2 isolates

Glycoprotein G (gG-2) of herpes simplex virus type 2 (HSV-2) is cleaved to a secreted amino-terminal portion and to a cell-associated, heavily O-glycosylated carboxy-terminal portion that constitutes the mature gG-2 (mgG-2). The mgG-2 protein is commonly used as a type-specific antigen in the serodiagnosis of HSV-2 infection. As the amino acid sequence variability of mgG-2 in clinical isolates may affect the performance of such assays, the gG-2 gene was sequenced from 15 clinical HSV-2 isolates. Few mutations were identified, and these were mostly localized outside the epitope regions described earlier. Five isolates were identical to different laboratory strains, indicating that the gG-2 gene is highly conserved over time. In the search for HSV-2 isolates harboring mutations within the immunodominant region of mgG-2, a pool of 2,400 clinical HSV-2 isolates was tested for reactivity with two anti-mgG-2 monoclonal antibodies (MAbs). Ten MAb escape HSV-2 mutants, which all harbored structurally restricted single- or dual-point mutations within the respective epitopes explaining the loss of binding, were identified. Sera from corresponding patients were reactive to mgG-2, as well as to a peptide representing the immunodominant region, suggesting that the point mutations detected did not diminish seroreactivity to mgG-2. The conservation of the gG-2 gene reported here further supports the use of mgG-2 as a type-specific antigen in the diagnosis of HSV-2 infections.