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This review outlines some of the many approaches taken over a decade or more to repair damaged hearts. We showcase the recent breakthroughs in organ regeneration elicited by reprogramming factors OCT3/4, SOX2, KLF4, and C-MYC (OKSM). Transient OKSM transgene expression rejuvenated senescent organs in mice. OKSM transgenes also caused murine heart cell regeneration. A triplet alanine mutation of the N-terminus of Serum Response Factor’s MADS box SRF153(A3), termed STEMIN, and the YAP mutant, YAP5SA synergized and activated OKSM and NANOG in adult rat cardiac myocytes; thus, causing rapid nuclear proliferation and blocked myocyte differentiation. In addition, ATAC seq showed induced expression of growth factor genes FGFs, BMPs, Notchs, IGFs, JAK, STATs and non-canonical Wnts. Injected STEMIN and YAP5SA synthetic modifying mRNA (mmRNA) into infarcted adult mouse hearts, brought damaged hearts back to near normal contractility without severe fibrosis. Thus, STEMIN and YAP5SA mmRNA may exert additional regenerative potential than OKSM alone for treating heart diseases.

Byline: I. Dinakar [INLINE:1] I attended Andhra Medical College, Vishakapatnam and graduated in 1959 as the most distinguished of the batch (Blue ribbon, Anderson gold medal). As an internee in [...]

Abstract HIV patients develop hepatic steatosis. We investigated hepatic steatosis in transgenic mice expressing the HIV-1 accessory protein Vpr (Vpr-Tg) in liver and adipose tissues, and WT mice infused with synthetic Vpr. Vpr-Tg mice developed increased liver triglyceride content and elevated ALT, bilirubin and alkaline phosphatase due to three hepatic defects: 1.6-fold accelerated de novo lipogenesis (DNL), 45% slower fatty acid ß-oxidation, and 40% decreased VLDL-triglyceride export. Accelerated hepatic DNL was due to coactivation by Vpr of liver X receptor-α (LXRα) with increased expression of its lipogenic targets Srebp1c, Chrebp, Lpk, Dgat, Fasn and Scd1, and intranuclear SREBP1c and ChREBP. Vpr enhanced association of LXRα with Lxrα and Srebp1c promoters, increased LXRE-LXRα binding, and broadly altered hepatic expression of LXRα-regulated lipid metabolic genes. Diminished hepatic fatty acid ß-oxidation was associated with decreased mRNA expression of Pparα and its targets Cpt1, Aox, Lcad, Ehhadh, Hsd10 and Acaa2, and blunted VLDL export with decreased expression of Mttp and its product microsomal triglyceride transfer protein. With our previous findings that Vpr circulates in HIV patients (including those with undetectable plasma HIV-1 RNA), co-regulates the glucocorticoid receptor and PPARγ and transduces hepatocytes, these data indicate a potential role for Vpr in HIV-associated fatty liver disease.

A young man was seen at a neurologic center for a slowly progressive myelopathy involving the lower limbs in 1983. After examination and investigations, a diagnosis of chronic tuberculous spinal arachnoiditis was made and the patient was administered antituberculous treatment. However, his condition continued to deteriorate. He was reviewed at another center in 1985, where a diagnosis of demyelinating disorder was made, for which he was treated. However, this also did not help, and he was diagnosed as having a nonspecific spinal arachnoiditis at yet another center in 1988. His condition continued to worsen, and after ten years of symptoms, when magnetic resonance imaging (MRI) was done, an intramedullary cystic lesion opposite D-12 vertebrae was seen, which on histopathology was proved to be a vascular malformation. After excision of the lesion his neurologic status has been slowly improving. The conditions that a malformation could mimic, misleading a clinician, and the role of MRI in clinching the diagnosis are highlighted. [ABSTRACT FROM AUTHOR]

Angiographically occult intracranial vascular malformations (AOIVM) are rare. Cerebral infarction due to AOIVM in the occipital lobe in an old person is also rare. The case of a fifty-year-old woman with a hemorrhagic infarction in the occipital lobe due to thrombosis of an AOIVM is reported. [ABSTRACT FROM AUTHOR]

A solitary case of angioblastic mening gioma hemangiopericytic variant occurring in a boy of five years has been reported. The symptoms, signs, investigations and treatment were discussed. The histology was typical of angioblastic meningioma. The boy deteriorated within a fortnight and passed away. [ABSTRACT FROM AUTHOR]

Angiographically occult intracranial vascular malformations (AOIVM) are rare. Cerebral infarction due to AOIVM in the occipital lobe in an old person is also rare. The case of a fifty-year-old woman with a hemorrhagic infarction in the occipital lobe due to throm bosis of an AOIVM is reported. [ABSTRACT FROM PUBLISHER]

A case of multiple brain abscess, one each in the temporal lobe, cerebellum and in the extradural space, treated successfully is reported. A careful clinical examination after drainage of the first abscess is necessary to identify and locate the subsequent ones, when they develop. The rarity of otogenic multiple in tracranial abscesses has been emphasised. [ABSTRACT FROM AUTHOR]

Conray-280 (meglumine iothalamate) can be injected safely into the cisterna magna in the human. In this series of 46 patients no complications were encountered attributable to the irritant effects of Conray. Satisfactory radiographic visualization was obtained in 87% of cases using 5 ml. 50% solution of Conray-280 enabling clear delineation of the anterior and posterior borders of the spinal cord to be made. [ABSTRACT FROM AUTHOR]